Gram negative

Nature, 1991 Jul 25, 352(6333), 342 - 4
Recognition and plasma clearance of endotoxin by scavenger receptors; Hampton RY et al.; Lipid A is the active moiety of lipopolysaccharide (LPS, also referred to as endotoxin), a surface component of Gram-negative bacteria that stimulates macrophage activation and causes endotoxic shock . Macrophages can bind, internalize and partially degrade LPS, lipid A and its bioactive precursor, lipid IVA . We report here that lipid IVA binding and subsequent metabolism to a less active form by macrophage-like RAW 264.7 cells is mediated by the macrophage scavenger receptor . Scavenger-receptor ligands inhibit lipid IVA binding to, and metabolism by, RAW cells, and lipid IVA binds to type I and type II bovine scavenger receptors on transfected Chinese hamster ovary cells . Although in vitro competition studies with RAW cells indicate that scavenger receptor binding is not involved in LPS or lipid IVA-induced stimulation of macrophages, in vivo studies show that scavenger-receptor ligands greatly inhibit hepatic uptake of lipid IVA in mice . Thus, scavenger receptors expressed on macrophages may have an important role in the clearance and detoxification of endotoxin in animals.

Ugeskr Laeger, 1991 Jul 22, 153(30), 2125 - 8
{Itching in the external ear--a side effect of ear plugs}; Madsen EF et al.; The object of this investigation was to assess the frequency of itching in the external auditory meatus in individuals who use hearing aid ear plugs (OP) and, simultaneously, to assess the cause of the itching . Seventy-six of the patients examined consecutively in the audiological department (ages 34-89 years) were questioned about itching and were submitted to an objective ear, nose and throat examination, audiometry and culturing from the external meatus for bacterial and fungal growth . In 20 patients, patch tests were made for allergic reactions from which the ear plugs were made (heat polymerized methyl methacrylate) . None of the 20 patients had become sensitized . Itching in the external auditory meatus was found to be a side effect of employment of ear plugs with an incidence of 39% as opposed to only seven in ears without ear plugs (p less than 0.05) . The incidence of itching was not reduced in ears with a ventilation channel in the ear plug . In 38% of the itching ears no objective changes were observed and, in the remaining cases, the changes were frequently limited . Potentially pathological bacterial growth was found to be significantly more in ears with ear plugs (1- greater than 16%, p less than 0.05) and in itching ears (4- greater than 24%, p less than 0.05) . In ears with potentially pathogenic bacteria, objective changes were nearly always found . In the vast majority of cases, the potentially pathogenic bacteria were Gram-negative, corresponding to the findings in external otitis in the tropics and mixed infections with fungi were frequently present.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood, 1991 Jul 15, 78(2), 387 - 93
Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples; Novotny WF et al.; Human plasma contains an inhibitor of tissue factor-initiated coagulation known as the lipoprotein-associated coagulation inhibitor (LACI) or also known as the extrinsic pathway inhibitor (EPI) . A competitive fluorescent immunoassay was developed to measure the plasma concentration of LACI in samples from normal individuals and patients with a variety of diseases . The LACI concentration in an adult control population varied from 60% to 160% of the mean with a mean value corresponding to 89 ng/mL or 2.25 nmol/L . Plasma LACI levels were not decreased in patients with severe chronic hepatic failure, warfarin therapy, primary pulmonary hypertension, thrombosis, or the lupus anticoagulant . Plasma LACI antigen was decreased in some, but not all patients with gram-negative bacteremia and evidence for disseminated intravascular coagulation . Plasma LACI levels were elevated in women undergoing the early stages of labor (29%), in patients receiving intravenous tissue-type plasminogen activator (45%), and in patients receiving intravenous heparin (375%) . A radioligand blot of the pre- and post-heparin plasma samples shows the increase to be in a 40-Kd form of LACI . Very low levels of plasma LACI antigen were found in patients with homozygous abetalipoproteinemia and hypobetalipoproteinemia, diseases associated with low plasma levels of apolipoprotein B containing lipoproteins . Following the injection of heparin into one patient with homozygous abetalipoproteinemia, the plasma LACI antigen level increased to a level comparable with that in normal individuals after heparin treatment.

Am J Ophthalmol, 1991 Jul 15, 112(1), 46 - 9
Ocular infections associated with Comamonas acidovorans; Stonecipher KG et al.; Comamonas acidovorans (Pseudomonas acidovorans) is a ubiquitous gram-negative rod . Although generally considered nonpathogenic, we found C . acidovorans to be associated with six cases of ocular infections . The organism was the only isolate in three cases, whereas an association of other organisms was present in three cases . The multiple resistance patterns of these strains to antibiotic susceptibility testing emphasizes the need for culturing ocular infections . We recommend the identification and susceptibility testing of all ocular gram-negative rod isolates.

Circ Shock, 1991 Jul, 34(3), 298 - 310
Characterization of an endotoxemic baboon model of metabolic and organ dysfunction; Lindsey DC et al.; An anesthetized endotoxemic baboon model has been developed by infusing 2.0 mg E . coli endotoxin/kg i.v . over 1 hr (n = 7) . Animals were monitored for 5-7 days with analyses of: cardiovascular, metabolic, and organ dysfunction; acid base, hemostatic, and hematological alterations; as well as tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels . Pathophysiologies detected at 2 hr included transient decreases in vascular resistance and blood pressure, a 157% increase in blood lactate, and a 90% decrease in circulating neutrophils . Organ dysfunction was not observed until 24 hr and, although thrombocytopenia was prevalent (-72% at 48 hr), disseminated intravascular coagulation (DIC) was not a major pathology . Hematocrit fell 21% by 24 hr and was -41% at 5-7 days . Serum TNF peaked at 90 min (7.8 +/- 0.2 ng/mL) and was undetectable after 3 hr . IL-6 also increased early, peaked at 3 hr (3872 +/- 846 U/mL) and was still detectable at 24 hr . A low mortality primate model of gram-negative sepsis has been developed that is characterized by early cardiovascular and metabolic dysfunction (2-6 hr), late organ dysfunction (24-48 hr), sub-clinical DIC, a prolonged anemia, and a 29% mortality between 48 and 72 hr.

J Biol Chem, 1991 Jul 5, 266(19), 12536 - 43
Interactions of plasmid-encoded replication initiation proteins with the origin of DNA replication in the broad host range plasmid RK2; Perri S et al.; The TrfA proteins, encoded by the broad host range plasmid RK2, are required for replication of this plasmid in a variety of Gram-negative bacteria . Two TrfA proteins, 33 and 44 kDa in molecular mass (designated TrfA-33 and TrfA-44, respectively), are expressed from the trfA gene of RK2 through the use of two alternative in-frame start codons within the same open reading frame . The two proteins have been purified from Escherichia coli to near homogeneity as a mixture of wild-type TrfA-44/33, as TrfA-33 alone and as a functional variant form of TrfA-44, designated TrfA-44(98L), which contains a leucine in place of the TrfA-33 methionine start codon . Cross-linking experiments demonstrated that TrfA-33 can multimerize in solution . By using gel mobility shift and DNase I footprinting techniques the binding properties of TrfA-33, TrfA-44(98L), and TrfA-44/33 to the origin of replication of plasmid RK2 were analyzed . All three protein preparations were able to bind very specifically to the cluster of five direct repeats (iterons) contained in the minimal origin of replication . Each protein preparation produced a ladder of TrfA/minimal oriV complexes of decreasing electrophoretic mobility . The DNase I protection pattern on the five iterons was identical for all three protein preparations and extended from the beginning of the first iteron to 5 base pairs upstream of the fifth iteron . Studies on the affinity of the proteins for DNA fragments containing one, two, or all five iterons of the origin revealed a strong preference of TrfA protein for DNA containing at least two iterons . To study the stability of TrfA.DNA complexes, association and dissociation rates of TrfA-33 and DNA fragments with one, two, or five iterons were measured . This analysis showed that unlike complexes involving two or five iterons the TrfA/one iteron complexes were highly unstable, suggesting some form of cooperativity between proteins or iterons in the formation of stable complexes and/or the requirement of specific sequences bordering the iterons at the RK2 origin of replication for the stabilization of TrfA/DNA complexes.

J Bacteriol, 1991 Jul, 173(14), 4503 - 9
Tet protein domains interact productively to mediate tetracycline resistance when present on separate polypeptides; Rubin RA et al.; Both domains, alpha and beta, of the cytoplasmic membrane-localized Tet proteins encoded by the tet gene family (classes A through E) are required for resistance to tetracycline (Tcr) in gram-negative bacteria . Two inactive proteins, each containing a mutation in the opposite domain, are capable of complementation to produce Tcr . Similarly, inactive hybrid proteins expressed by interdomain gene hybrids constructed between tet(B) and tet(C) {tet(B) alpha/(C) beta and tet(C) alpha/(B) beta} together produce significant Tcr via trans complementation (R.A . Rubin and S . B . Levy, J . Bacteriol . 172:2303-2312, 1990) . A derivative of tet(B) was constructed to express the two domains of Tet(B) as separate polypeptides, neither containing intact the central, hydrophilic interdomain region . Cells harboring this tet(B) mutant expressed Tcr at about 20% the level conferred by intact tet(B) . As expected, no detectable amount of a full-length Tet protein was expressed . A polypeptide corresponding to the alpha domain was observed . Interdomain hybrids between tet(B) and tet(C) containing a frameshift at the fusion junction, designed to result in expression of each of the four domains on separate polypeptides, showed trans complementation without production of detectable full-length proteins . Levels of Tcr were greater than or equal to those previously observed in complementations using full-length hybrid proteins . These results strongly suggest that polypeptides harboring individual alpha and beta domains, lacking an intact interdomain region, can interact productively in the cell to confer Tcr.

Infect Immun, 1991 Jul, 59(7), 2505 - 7
The heat-modifiable outer membrane protein of Actinobacillus actinomycetemcomitans: relationship to OmpA proteins; Wilson ME; The outer membrane of Actinobacillus actinomycetemcomitans contains a 29-kDa protein which exhibits heat modifiability on sodium dodecyl sulfate-polyacrylamide gels and represents a major target for immunoglobulin G antibody in sera of periodontitis patients colonized by this organism . In the present study, the N-terminal amino acid sequence of the 29-kDa outer membrane protein was determined and compared with reported sequences for other known proteins . The heat-modifiable outer membrane protein of A . actinomycetemcomitans was found to exhibit significant N-terminal homology with the OmpA proteins of other gram-negative bacteria . Moreover, this protein reacted with antiserum raised against the purified OmpA protein of Escherichia coli K-12 . Whether the heat-modifiable OMP of A . actinomycetemcomitans also shares functional properties of OmpA proteins, particularly with respect to bacteriophage receptor activity, is presently under investigation.

Res Microbiol, 1991 Jul-Aug, 142(6), 705 - 10
Diversity of the mechanisms of resistance to beta-lactam antibiotics; Frere JM et al.; The sensitivity of a bacterium to beta-lactam antibiotics depends upon the interplay between 3 independent factors: the sensitivity of the essential penicillin-binding enzyme(s), the quantity and properties of the beta-lactamase(s) and the diffusion barrier that the outer-membrane of Gram-negative bacteria can represent . Those three factors can be modified by mutations or by the horizontal transfer of genes or portions of genes.

DICP, 1991 Jul-Aug, 25(7-8), 778 - 83
Human monoclonal antibody against endotoxin; Zarowitz BJ; Little progress has been made over the past several years in the treatment of gram-negative bacteremia and septic shock . Advances in biotechnology have led to the development of human monoclonal antibody against endotoxin (HA-1A), a toxic mediator of the septic response . HA-1A is an immunoglobulin M antibody to the lipid A component of the endotoxin molecule . It distributes into an apparent volume of distribution 10-20 percent larger than plasma volume and has a circulating half-life of 16.0 hours . In a major, multicenter, double-blind trial of HA-1A 100 mg administered intravenously versus placebo, mortality was greatly reduced in HA-1A recipients with gram-negative bacteremia . Increased survival was noted early and was sustained throughout the 28-day study period in patients with and without shock at the time of enrollment . HA-1A has an excellent safety profile; thus far only two minor hypersensitivity reactions and no drug interactions have been reported . Based on currently available information, the release of HA-1A as adjunct therapy for patients with gram-negative bacteremia with or without shock represents a significant therapeutic advance . Investigations are underway to define the optimal dose of HA-1A and its duration of action . Comparative trials between HA-1A and competitive products are necessary.

DICP, 1991 Jul-Aug, 25(7-8), 741 - 2
Stability of ceftriaxone sodium in peritoneal dialysis solutions; Nahata MC; Continuous ambulatory peritoneal dialysis is used commonly in patients with endstage renal disease . Infection is the most frequent complication of this dialysis . To treat certain infections caused by gram-negative microorganisms, ceftriaxone sodium may be added to the peritoneal dialysate fluid . No data are available, however, about ceftriaxone's stability at various temperatures in dialysate solutions containing dextrose 1.5 and 4.25% . The objective of this study was to determine the stability of ceftriaxone in dialysis solutions containing dextrose 1.5 and 4.25% over 14 days at 4 degrees C, 5 days at 23 degrees C, and 24 hours at 37 degrees C . Ceftriaxone 500 mg was added to 36 dialysate bags (500 mL); six bags of each of two dextrose concentrations were stored at each of the three temperatures . The samples were collected at 0, 3, 7, 10, and 14 days at 4 degrees C; 0, 1, 2, and 5 days at 23 degrees C; and 0, 6, 12, and 24 hours at 37 degrees C . Ceftriaxone was measured by a specific, stability-indicating HPLC method . A clinically significant loss of potency was defined as a greater than ten percent decrease from its initial concentration . The mean ceftriaxone concentration was 90 percent or more of the initial concentration for 14 days at 4 degrees C, 24 hours at 23 degrees C, and 6 hours at 37 degrees C . Thus, ceftriaxone can be stored in dialysate solutions for 14 days under refrigeration, 24 hours at room temperature, and 6 hours at body temperature.

Mol Microbiol, 1991 Jul, 5(7), 1599 - 606
Regulation of capsular polysaccharide synthesis in Escherichia coli K12; Gottesman S et al.; Synthesis of the capsular polysaccharide colanic acid in Escherichia coli K12 is regulated by a complex network of regulatory proteins . This regulation is expressed at the level of transcription of the cps (capsular polysaccharide synthesis) genes . Two positive regulators, RcsA and RcsB, are necessary for maximal capsule expression . The availability of RcsA is normally limited because the RcsA protein is rapidly degraded by the Lon ATP-dependent protease . Therefore Lon acts, indirectly, as a negative regulator of capsule synthesis . The sequence predicted for RcsB suggests that it is the effector component of a two-component system; a protein with homology to sensors, RcsC, also plays a role in capsule regulation . We propose a model for capsule synthesis in which RcsA interacts with RcsB to stimulate transcription of the cps genes . The mechanism of regulation of colanic acid synthesis in E . coli may apply to other capsules in a variety of Gram-negative bacteria.

Exp Lung Res, 1991 Jul-Aug, 17(4), 743 - 61
In vivo effects of endotoxin on nasal epithelial mucosubstances: quantitative histochemistry; Harkema JR et al.; Airway inflammation induced by gram-negative bacteria is often characterized by an influx of neutrophils and hypersecretion of mucus . The purpose of this study was to determine how endotoxin, a component of gram-negative bacteria and a chemotaxinogen for neutrophils, affects the amount of stored intraepithelial mucosubstances in the rat nasal airway . Rats were intranasally instilled, once a day for 3 days, with endotoxin or saline (controls) . Before the first and third instillation, half of the animals were depleted of circulating blood neutrophils by administering a rabbit anti-rat neutrophil antiserum . Rats were sacrificed 6 or 24 h after the last instillation . Nasal tissues were processed for light microscopy and histochemical detection of stored intraepithelial mucosubstances . The numbers of nasal epithelial cells and intraepithelial neutrophils per millimeter of basal lamina in the anterior nasal septum and the amounts of intraepithelial mucosubstances in the same nasal tissue were determined by image analysis . We did not observe a neutrophil influx in the nasal tissues of neutrophil-depleted rats at 6 or 24 h after the last endotoxin instillation; however, we did observe a significant increase in intraepithelial mucosubstances, compared to saline-instilled controls . In contrast, nonneutrophil-depleted animals had a marked neutrophilic influx and a concomitant decrease in stored mucosubstances, compared to saline-instilled controls . There was no significant difference in the number of nasal epithelial cells per millimeter of basal lamina among any of the experimental groups . These results indicate (1) that endotoxin induces an increase in the amount of intraepithelial mucosubstances only when intraepithelial neutrophils are absent, and (2) that the endotoxin-induced, neutrophil influx probably triggers mucous hypersecretion.

J Submicrosc Cytol Pathol, 1991 Jul, 23(3), 447 - 55
Rickettsiae and giant lysosomes in the testes of Temnocephala novaezealandiae (Platyhelminthes: Temnocephaloidea); Williams JB; Rickettsiae are concentrated in the testes of Temnocephala novaezealandiae, where they occupy the cytoplasm of spermatogenetic stages and the testis epithelia . They have gram negative ultrastructural characteristics and are surrounded by clear zones which are not membrane-limited; indented mitochondria are associated with the clear zones . Propagation occurs by simple division . Extensions of the testis epithelium envelop cloned groups of spermatocytes, spermatids and spermatozoa . Heterophagosomes isolating unmodified rickettsiae, and giant lysosomes enclosing bacteria in advanced stages of degradation, are contained within the epithelial processes . Rickettsiae and large lysosomes were found also in testes of Troglocaridicola mrazeki, a scutariellid . Peririckettsial lucid zones are interpreted as areas of histopathy where host cytoplasm has been catabolized by bacterial enzymes . The rickettsiae evidently are true parasites, although they have no apparent harmful effect on the general condition of their hosts . Digestion of bacteria in lysosomes may provide nutrients for spermatogenetic stages . Transmission of rickettsiae to juvenile temnocephalids does not occur via the spermatozoa.

Am J Med, 1991 Jul, 91(1), 23 - 9
High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines . The Swiss-Dutch J5 Immunoglobulin Study Group; Calandra T et al.; PURPOSE AND PATIENTS: We measured the serum concentrations of interleukin-6 (IL-6) in 70 patients with established septic shock caused predominantly by gram-negative bacteria . The aims of the study were to determine whether and for how long IL-6 was detectable in the circulation of these patients, to assess whether IL-6 levels were associated with patients' outcomes, and, finally, to examine the interplay between IL-6, tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma) . RESULTS: IL-6 was detected in 64% of the patients at study entry but in only 18% on Day 1 and 2% on Day 10 . Serum levels of IL-6 were higher (median: 3.5 ng/mL, range: less than 0.1 to 305 ng/mL) in patients dying of fulminant septic shock than in those surviving (median: 0.5 ng/mL, range: less than 0.1 to 135 ng/mL; p = 0.003) or in those with a transient reversal of shock but who ultimately died of a relapse of shock (median: less than 0.1 ng/mL, range: less than 0.1 to 12.5 ng/mL; p = 0.005) . However, no cutoff values of IL-6 confidently predicted the outcome of an individual patient . The serum concentrations of IL-6 measured at study entry correlated with the duration of survival (r = -0.51, p = 0.004) and with the levels of TNF-alpha (r = 0.53; p less than 0.0001) but not with the levels of either IL-1 beta (r = 0.01, p = 0.90) or IFN-gamma (r = 0.06, p = 0.60) . CONCLUSIONS: These results indicate that circulating levels of IL-6 are detectable in a majority of patients with gram-negative septic shock . Concentrations of IL-6 peaked near the onset of shock and rapidly decreased to undetectable levels within approximately 24 hours in most patients . Levels of IL-6 measured at study entry correlated with levels of TNF and with patients' outcomes . Yet, IL-6 does not appear to be a clinically useful laboratory test for predicting the outcome of an individual patient.

Clin Microbiol Rev, 1991 Jul, 4(3), 286 - 308
The tribe Ehrlichieae and ehrlichial diseases; Rikihisa Y; The tribe Ehrlichieae consists of gram-negative minute cocci that are obligate intracellular parasites classified in the family Rickettsiaceae . Although ehrlichial organisms have been observed in leukocytes for many years, only a few species have been cultured in quantities sufficient for biochemical and molecular analyses . Recents studies on 16S-rRNA sequence analysis and energy metabolism showed that the genus Ehrlichia is closely related to the genus Rickettsia . There is, however, no antigenic cross-reactivity between these genera . Ehrlichial organisms cause a disease called "ehrlichiosis," a noncontagious infectious disease known to be transmitted by a tick in several cases and by a fluke in one case . Ehrlichia spp . infect dogs, ruminants, horses, and humans . Recently, two new ehrlichial diseases, Potomac horse fever and human ehrlichiosis, were discovered in the United States . The etiologic agent of Potomac horse fever, Ehrlichia risticii, is closely related to the known human pathogen Ehrlichia sennetsu . The etiologic agent of human ehrlichiosis is related to Ehrlichia canis, a canine pathogen . In contrast to the genus Rickettsia, members of the tribe Ehrlichieae reside primarily in the cytoplasmic vacuoles of monocytes or granulocytes and cause hematologic abnormalities, lymphadenopathy, and other pathologic changes in the host . However, the actual mechanisms whereby Ehrlichia spp . infect leukocytes, multiply in them, and produce various forms of systemic disease have not been defined . Depending on the ehrlichial species involved, serologic or direct microscopic observation of stained blood smears is currently used to diagnose ehrlichial disease.

J Invertebr Pathol, 1991 Jul, 58(1), 75 - 81
Extracellular giant rickettsiae associated with bacteria in the gill of Crassostrea gigas (Mollusca, Bivalvia); Azevedo C et al.; Extracellular giant rickettsiae closely associated with bacteria with a Gram-negative type wall are reported among the basal insertions of the cilia of the gill epithelium of the oyster Crassostrea gigas (Mollusca, Bivalvia) from the north of Spain . These rickettsiae are extremely pleomorphic cells with a maximum 9 microns length . The internal elements are ribosome-like particles and DNA strands are distributed in some light areas . Some rickettsial cells show one to two vacuole-like dense inclusions formed by curved concentric bands approximately 4 nm thick separated by an approximately 5-nm light space (myelin-like bodies) . Numerous bacteria are closely associated with the rickettsiae in the surrounding zone . The cytopathic effects of this association seemed to give rise to the epithelial lysis and concomitant disappearance of the apical microvilli and cilia and the consequent destruction and disintegration of the gill epithelial cells, where these rickettsiae live in close proximity . This is believed to be the first description of extracellular giant pathogenic rickettsiae of these oyster species.

J Laryngol Otol, 1991 Jul, 105(7), 582 - 3
Parapharyngeal space melioidosis in a diabetic; Elango S et al.; Pseudomonas pseudomallei, a gram negative organism causing melioidosis, is found in tropical and subtropical regions . It may manifest as a pulmonary lesion, osteomyelitis, soft tissue abscesses, abscesses in various organs or in septicaemic form . Melioidosis of the parapharyngeal space has not been reported so far . A case of melioidosis of the parapharyngeal space which was successfully treated by drainage and prolonged antibiotic therapy is reported here . Melioidosis should be suspected in severe forms of deep neck space infection, especially if the patient comes from an endemic area.

J Periodontal Res, 1991 Jul, 26(4), 308 - 13
Black-pigmenting gram-negative bacteria in periodontal disease . II . Screening strategies for detection of P . gingivalis; Mombelli A et al.; The purpose of this analysis was to evaluate the feasibility of detecting P . gingivalis using selected sites and to indicate increased proportions of this organism in periodontitis patients . In 10 patients suffering from moderate to advanced periodontal disease, separate microbiological samples were taken from the mesial, buccal, distal and oral (lingual or palatal) aspects of every tooth . This yielded a total of 927 microbiological samples, 84 to 102 per patient . Three distinct patterns of distribution and relative proportion of P . gingivalis were recognized . In one group of patients, the organism was not cultured . In a second group, few positive sites with low proportions of P . gingivalis were present . A third group of patients yielded high frequencies and proportions of P . gingivalis . The number of samples necessary to diagnose the presence of P . gingivalis at a 95% confidence level varied considerably between the three groups . In 4 patients, sampling 4 randomly selected sites was sufficient, while in the remaining 3 positive patients, 25 or more samples were required to detect the organism with equal certainty . Seven different protocols for multiple subgingival sampling were studied . When considering the number of samples needed to detect the presence of P . gingivalis and to estimate the highest proportion of this organism, selection of the deepest pocket in each quadrant was the most efficient method of sampling.

J Periodontal Res, 1991 Jul, 26(4), 301 - 7
Black-pigmenting gram-negative bacteria in periodontal disease . I . Topographic distribution in the human dentition; Mombelli A et al.; The purpose of this study was to determine the distribution of black-pigmenting Gram-negative bacteria in the dentition of periodontitis patients and to examine differences in the microbial composition of samples taken from a series of adjacent sites . Separate subgingival samples were taken from the mesial, buccal, distal and oral aspects of every tooth in 10 subjects . Thus, a total of 927 sites, 84 to 102 per patient, were scored clinically and sampled microbiologically . P . intermedia and P . melaninogenica were found in all subjects . P . gingivalis was found in 7 . The organisms tended to be distributed unevenly, giving the impression of clusters of positive samples in certain areas of the dentition . 77% of all samples positive for P . gingivalis were also P . intermedia-positive . Premolars had lower frequencies and mean proportions of P . gingivalis than incisors and molars . In the premolar and molar region, frequencies and mean proportions of P . gingivalis increased with more posterior location . While frequencies indicated a similar topographic distribution of P . intermedia the mean proportions of this organism were more consistent at different locations . Based on a logistic regression model, it was estimated that the probability of detecting P . gingivalis was 34 times higher in any site which had at least 1 P . gingivalis-positive neighboring site . For P . intermedia any site with at least 1 P . intermedia-positive neighboring site had a chance 2.4 times higher of harboring the organism as well . The highest chance of detecting P . gingivalis and P . intermedia existed in deep, oral pockets of molars, which bled upon sampling.

J Med Assoc Thai, 1991 Jul, 74(7), 288 - 92
Efficacy of dosage schedule for rational dosage prescribing of gentamicin; Thamlikitkul V et al.; In our pilot study of 30 patients who were on gentamicin, the adequate peak level (5-10 mg/dl) was found in 27 per cent, trough level (less than 2 mg/dl) in 67 per cent and both peak and trough level in only 10 per cent . We have several reasons to believe that it is due to inappropriate dosage prescribing . The objective of the study is to test the efficacy of using a recommended dosage schedule for rational dosage prescribing of gentamicin . All medical residents were invited to attend a 2-hour session on gentamicin pharmacokinetics . The problems and the use of recommended dosage schedule were extensively discussed . Then serum gentamicin levels were re-monitored by Fluorescence Polarization Immunoassay (TDx) . Of 73 gentamicin recipients, 39 (53%, C gr.) were given at the correct dosage according to the schedule and 34 (47%, IC gr) were given incorrectly . The characteristics of the patients in both groups were not different . The appropriate peak, trough, peak and trough levels in C gr were 87, 80, 67 per cent respectively compared with 24, 80 and 9 per cent in the IC group, p less than 10(-4) for peak, peak and trough . The incidence of nephrotoxicity was not different between the two groups . The patients' outcomes were difficult to assess because most of the patients received antibiotic combinations . However, case fatality of documented gram-negative infection tended to be less in the C group . It is concluded that dosage schedule can improve rational dosage prescribing of gentamicin . Most of the patients given gentamicin may not need monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Infect Dis, 1991 Jul-Aug, 13(4), 666 - 87
University of California/Davis Interdepartmental Conference on gram-negative septicemia; Young LS et al.; Gram-negative septicemia remains one of the most serious forms of hospital-acquired infection . The most consistently virulent component of the gram-negative lipopolysaccharide (endotoxin) appears to be lipid A . Elucidation of the structure-function relationships of lipid A and the biochemical configurations required for endotoxicity makes possible the design of lipopolysaccharide antagonists and/or the production of poly- or monoclonal antibodies that may abrogate the biologic effects of endotoxin . The mechanisms of activity of lipopolysaccharide and the pathophysiologic events it triggers are now better understood than in the recent past . Lipid A triggers the release of mediators such as cachectin (tumor necrosis factor), thereby initiating a cascade of potentially lethal events . Although recent studies indicate no routine role for corticosteroids in gram-negative septic shock or acute respiratory distress syndrome, considerable progress has been made in the development of effective antibiotics . Recent studies of septicemia in neutropenic patients show survival rates significantly higher than those reported more than two decades ago.

Am Rev Respir Dis, 1991 Jul, 144(1), 202 - 7
Characteristics of aerobic gram-negative bacteria colonizing critically ill patients; Donaldson SG et al.; Adherence of gram-negative bacteria (GNB) to epithelial surfaces is important for GNB colonization to occur . Pili, rodlike structures projecting from the outer membrane of GNB, and GNB surface hydrophobicity have been shown to enhance GNB adherence . We investigated the types of pili and the hydrophobicity of aerobic GNB colonizing the stomach, oropharynx, and trachea of critically ill patients . Piliation and hydrophobicity of oral, tracheal, and gastric GNB were compared with that of commensal GNB isolated from patients' rectums . Significantly more oropharyngeal than rectal GNB were piliated, and the most common type of pili present was type 1, or mannose-sensitive pili . Mannose-resistant and P pili were present less often, and no colonizing GNB had S pili . Colonizing GNB were hydrophilic rather than hydrophobic, and no differences in hydrophobicity were noted between colonizing GNB and rectal isolates . Our results suggest that pili may be important for oropharyngeal GNB colonization.

J Bacteriol, 1991 Jul, 173(13), 4195 - 202
Fragmentation of Escherichia coli type 1 fimbriae exposes cryptic D-mannose-binding sites; Ponniah S et al.; Cells of the gram-negative bacterium Escherichia coli are able to attach to various host cells by means of a mannose-specific adhesin associated with type 1 fimbriae . Here we show that fragmentation of type 1 fimbriae by freezing and thawing results in increased mannose-binding activity as demonstrated by increased hemagglutination, increased stimulation of human lymphocyte proliferation, and increased binding of the mannose-containing enzyme horseradish peroxidase . Increased activity in all three assays was mannose sensitive and was not exhibited by FimH- mutant type 1 fimbriae lacking the adhesin . Scatchard analysis of the data from peroxidase binding assays showed that unfrozen and frozen fimbriae contain binding sites displaying two classes of affinity . Frozen and thawed fimbriae expressed an increase in the number of high-affinity binding sites . These results show that fragmentation of the fimbrial structure exposes cryptic mannose-binding activity associated with type 1 fimbriae, presumably that of internally located adhesin molecules . Our data support earlier observations that adhesin moieties of type 1 fimbriae are located both at the tips and at intervals along the length of the fimbriae . In addition, our data suggest that only the adhesin moieties that are located at the fimbrial tips are functional in binding mannose . Adhesins located along the length of the fimbriae have their mannose-binding activity buried within the fimbrial structure and hence are not functional . We propose an updated model for the structure of type 1 fimbriae that is in agreement with the above observations.

FEMS Microbiol Lett, 1991 Jul 1, 65(3), 261 - 4
An improved aminoglycoside resistance gene cassette for use in gram-negative bacteria and Streptomyces; Denis F et al.; A cloning cassette, carrying a modified amino-glycoside resistance gene (neo) from transposon Tn5 was constructed . Three restriction sites internal to the neo gene were eliminated by in vitro mutagenesis, allowing their use in designing new cloning vectors . The original, suboptimal transcription promoter was replaced with a synthetic sequence corresponding to the consensus for E . coli and Streptomyces promoters . The cassette has numerous restriction sites for easy subcloning of the promoter, the coding sequence or the whole gene.

Eur J Pediatr, 1991 Jul, 150(9), 665 - 8
Vitamin D dependent rickets type II with myelofibrosis and immune dysfunction; Walka MM et al.; We present a new patient with vitamin D dependent rickets type II . A 20-month-old Arabian boy whose parents are first cousins showed florid rickets, myelofibrosis and recurrent septicaemia . In addition to absent specific binding for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) . 25-Hydroxyvitamin D3-24-hydroxylase activity could not be induced in cultured fibroblasts . The patient did not respond to 99 micrograms 1,25(OH)2D3 per day, but skeletal and haematological abnormalities improved with daily infusion of 100 mg/kg calcium, as serum parathyroid hormone levels fell to normal values . At the age of 7 years, he died from pneumonia . The improvement of haematological abnormalities with calcium infusions but not with 1.25(OH)2D3 suggests a pathogenetic relationship of myelofibrosis and hyperparathyroidism . Having anti-lipid A IgM antibody titres up to 1:10.000 after Gram negative septicaemias, the patient never produced corresponding IgG antibodies . His neutrophil chemotaxis was persistently reduced to 57% +/- 3% of age-matched controls (P less than 0.028) . The patient showed two pathological immune functions considered to contribute to the well-known susceptibility to infection in rickets.

J Bacteriol, 1991 Jul, 173(14), 4493 - 502
Characterization of the nonenzymatic chloramphenicol resistance (cmlA) gene of the In4 integron of Tn1696: similarity of the product to transmembrane transport proteins; Bissonnette L et al.; Integrons constitute a novel family of DNA elements which evolved by site-specific integration of discrete units between two conserved segments . On the In4 integron of Tn1696, a precisely inserted gene cassette of 1,549 bp conferring nonenzymatic chloramphenicol resistance (cmlA) is present between the streptomycin-spectinomycin resistance (aadA2) gene cassette and the 3'-conserved segment of the integron . In this study, we present the nucleotide sequence of the cmlA gene cassette of Tn1696, show its similarity to bacterial efflux systems and other transport proteins, and present evidence for alterations that its expression exerts on bacterial membranes . The cmlA gene cassette apparently carries its own promoter(s), a situation that has not heretofore been observed in the integrons of multiresistance plasmids and transposons of gram-negative bacteria . One or more of these promoters were shown to be functionally active in expressing a cat marker gene from promoter-probe vectors . The putative CmlA polypeptide appears to provoke a reduction of the content of the major porins OmpA and OmpC.

Infect Immun, 1991 Jul, 59(7), 2252 - 8
Outer membrane protein A (OmpA) contributes to serum resistance and pathogenicity of Escherichia coli K-1; Weiser JN et al.; We examined whether outer membrane protein A (OmpA) contributes to gram-negative pathogenesis by determining the effect of mutagenesis of ompA in a virulent Escherichia coli K-1 isolate . An OmpA mutant was generated by insertion of the transposon TnphoA, which was genetically modified to increase the efficiency of its delivery by conjugation . The mutant was less virulent than its parent strain in two models of E . coli K-1 infection . Equal inocula of the OmpA+ and OmpA- strains fed to neonatal rats resulted in a sevenfold-greater incidence of bacteremia at 72 h from the OmpA+ strain . The lethal effect of the OmpA- mutant was significantly less than that of the OmpA+ parent strain when inoculated onto the chorioallantoic membrane of 10-day embryonated chick eggs . There was, however, no difference between strains in growth characteristics under physiologic conditions, either in rat serum or in unembryonated chick eggs . In the presence of a 10-day chick embryo, there was a 10-fold increase in the survival and growth of the OmpA+ strain . Correction of the mutation in ompA with an E . coli K-12 ompA gene restored a level of virulence equivalent to that of the parent strain . The ompA mutant was more sensitive to the bactericidal effect of pooled human serum by the classical pathway of complement activation . These results suggest that OmpA contributes to E . coli K-1 pathogenesis by a mechanism which may involve increased serum resistance.

Oral Surg Oral Med Oral Pathol, 1991 Jun, 71(6), 689 - 95
Salivary secretion rate, yeast cells, and oral candidiasis in patients with acute leukemia; Wahlin YB; Stimulated salivary secretion rate was repeatedly determined in 29 patients with acute leukemia during two periods of cytotoxic treatment in myelosuppressive doses . For comparison, the salivary secretion rate was studied in 83 healthy persons and in three other groups of hospitalized patients without malignant disorders . At the start of cytotoxic treatment the secretion rate in the patients with leukemia was lower than in healthy persons . The rate fell significantly after 1 to 3 days and later rose to the level seen in the healthy persons . Several interacting factors may have contributed to the decrease in salivary secretion rate, but the most important factor was probably the use of antiemetic drugs during the first 3 days of the study periods . No relationship was found between salivary secretion rate and the number of gram-negative rods found in the mouth . Patients with low salivary secretion rates had high numbers of yeast cells and more often oral candidiasis.

Am J Pathol, 1991 Jun, 138(6), 1485 - 96
The intratracheal administration of endotoxin and cytokines . I . Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate; Ulich TR et al.; Endotoxin (LPS), one of the major proinflammatory constituents of the cell walls of gram-negative bacteria, induces alveolar macrophages to express interleukin-1 (IL-1) and tumor necrosis factor (TNF) messenger RNA (mRNA), peaking at 1 hour in vitro . Intratracheal injection of LPS induces IL-1 and TNF mRNA expression in vivo in whole-lung RNA preparations . Interleukin-1 mRNA is not constitutively detected . In the case of TNF, however, a constitutively-expressed hybridization band is noted at 1.6 kb, whereas the LPS-induced hybridization band is noted at approximately 1.95 kb . Intratracheal injection of LPS induces an intra-alveolar inflammatory reaction composed of a neutrophilic exudate, peaking at 6 to 12 hours, a monocytic exudate peaking at 24 hours, and a lymphocytic exudate peaking at 48 hours, as quantitated by bronchoalveolar lavage . Intratracheal injection of IL-1 recapitulates the kinetics and relative magnitudes of the acute neutrophilic and chronic monocytic and lymphocytic inflammatory sequence . Intratracheal injection of TNF also induces an acute intraalveolar neutrophilic exudate, but TNF is much less potent of an inflammatory stimulus than IL-1 . The effects of recombinant IL-1 and TNF are not due to LPS contamination, as shown by abrogation of the cytokines' inflammatory activity by boiling . In conclusion, LPS induces IL-1 and TNF mRNA expression in vitro in alveolar macrophages and in vivo in pulmonary tissue, and intratracheal injection of IL-1 and TNF recapitulates the LPS-induced pulmonary inflammatory sequence, strongly supporting the hypothesis that these cytokines play an important in vivo role in the pathogenesis of gram-negative bacterial pneumonia.

Surgery, 1991 Jun, 109(6), 698 - 705
Tumor necrosis factor and interleukin-1 protection against the lethal effects of tumor necrosis factor; Sheppard BC et al.; Based on the hypothesis that tumor necrosis factor (TNF) causes the lethality of gram-negative sepsis and previous work of tolerance to the lethal effects of TNF induced by repetitive exposure to sublethal intraperitoneal doses of human recombinant (r) TNF, we studied the protective role of a single sublethal intravenous dose of either rTNF (100 micrograms/kg) or recombinant interleukin-1 (rIL-1; 10(5) units/kg) or both before a subsequent lethal intravenous dose of rTNF (800 to 1000 micrograms/kg) in C3H/HEN mice . Mice were treated with a single intravenous dose of saline, rTNF, rIL-1 or both cytokines and challenged within 2 hours to 10 days with a lethal dose of rTNF . Mice treated with rTNF showed significant protection against the lethal effects of TNF when the treatment dose was given only 2 hours before the lethal dose, but maximal protection required a 24-hour interval and lasted as long as 8 days . The treatment dose of rTNF was toxic, and it resulted in occasional treatment deaths . Mice treated with rIL-1 showed maximal protection when treatment was given only 2 hours before challenge and protection lasted for 8 days . No toxicity was apparent secondary to IL-1 treatment . The combination of rIL-1 and rTNF was not as effective as either cytokine alone . The results suggest that rTNF or rIL-1 may be clinically useful in the prevention and treatment of sepsis lethality by the induction of tolerance to the lethal effects of TNF . The more promising cytokine appears to be rIL-1 because it has less toxicity and more rapid induction of full therapeutic effectiveness.

Toxicol Appl Pharmacol, 1991 Jun 1, 109(1), 51 - 9
Increased endotoxin sensitivity following T-2 toxin treatment is associated with increased absorption of endotoxin; Taylor MJ et al.; Oral exposure to T-2 Toxin (T-2) in experimental animals results in a syndrome similar to that observed in endotoxemia . Endotoxins are lipopolysaccharide, outer-membrane components of gram-negative bacteria which induce acute, inflammatory responses . In the present study, several aspects of endotoxin pathophysiology were investigated in mice following simultaneous exposure to T-2 and endotoxin, including mortality, hypothermia, tumor necrosis factor-alpha (TNF-alpha) and corticosterone production, and thymic weight . The disposition of endotoxin was also assessed, Acute, simultaneous exposure to T-2 (4 mg/kg, po) and endotoxin (3 micrograms/mouse, ip) resulted in increased mortality, hypothermia, TNF-alpha production, and thymic atrophy compared to treatment with either T-2 of endotoxin alone . Pretreatment of mice with endotoxin, a regime that renders the animals resistant to the effects of endotoxin, reduced many endotoxin effects in animals treated simultaneously with T-2 and endotoxin . Upon further investigation, it was observed that T-2 increased the absorption rate of endotoxin: as the peak height of serum endotoxin increased, the time-to-peak decreased, and the area under the curve was unchanged in animals treated simultaneously with T-2 and endotoxin . It was concluded that increased endotoxin absorption accounted for the increases in mortality, hypothermia, and TNF-alpha associated with T-2 exposure.

Q J Med, 1991 Jun, 79(290), 517 - 25
Perspectives in multiple myeloma: survival, prognostic factors and disease complications in a single centre between 1975 and 1988; Rayner HC et al.; One hundred and forty-one patients with multiple myeloma, diagnosed at the City Hospital, Nottingham between January 1975 and October 1986, were followed until death or for at least two years in a retrospective study . Overall median survival was 25 months, with no significant improvement occurring during the study period; increasing age, ESR and serum creatinine concentration at diagnosis were independent predictors of shortened survival . Renal impairment developed in 56 per cent of patients but only 7 per cent died of renal failure . At least one episode of infection occurred in 55 per cent of patients, most commonly in the first month . There was a significant rise in the overall incidence of infection and in the proportion caused by Gram-negative bacteria during the study period . Raised serum urea and low haemoglobin concentrations at diagnosis were independent risk factors for subsequent infection . Infection was associated with 2.75-fold increased risk of death, independent of other risk factors . Prevention of infection is an important aim for improvements in the survival of patients in multiple myeloma.

J Antimicrob Chemother, 1991 Jun, 27(6), 707 - 12
Cloning of the type Ib trimethoprim-resistant dihydrofolate reductase gene and preparation of a specific biotinylated DNA probe; Qumsieh MJ et al.; A 3.0-kb PstI/HindIII fragment encoding the type Ib trimethoprim-resistant dihydrofolate reductase (DHFR) was cloned into pUC18 . Following successive subcloning, the type Ib DHFR gene was identified within a 500 bp HincII fragment . The 500 bp fragment was purified, biotinylated and tested for its suitability as a specific DNA probe in non-isotopic hybridisation experiments with standard plasmids carrying genes for the available known Gram-negative DHFR types . Under conditions of high stringency the probe was specific for the type Ib gene and hence will be useful for monitoring the spread of this particular trimethoprim resistance gene.

J Bacteriol, 1991 Jun, 173(11), 3591 - 6
Acyl-acyl carrier protein specificity of UDP-GlcNAc acyltransferases from gram-negative bacteria: relationship to lipid A structure; Williamson JM et al.; Lipid A, the component of lipopolysaccharide that provides the membrane anchor of the core and O-antigen sugars, is known to contain characteristic R-3-hydroxy fatty acids bound to the 2,2' (N-linked) and 3,3' (O-linked) positions of the glucosamine disaccharide in different gram-negative bacteria . The studies reported here show that it is the acyl-acyl carrier protein specificities of the enzymes UDP-GlcNAc-O-acyltransferase and UDP-3-O-{(R)-3-hydroxyacyl}-GlcN-N-acyltransferase that determine the nature of these fatty acids.

J Bacteriol, 1991 Jun, 173(11), 3342 - 55
Behavior of peripheral rods and their role in the life cycle of Myxococcus xanthus; O'Connor KA et al.; Myxococcus xanthus is a gram-negative bacterium with a complex life cycle including a developmental phase in which cells aggregate and sporulate in response to starvation . In previous papers, we have described a heretofore unsuspected layer of complexity in the development of M . xanthus: vegetatively growing cells differentiate into two cell types during development . In addition to the differentiation of spores within fruiting bodies, a second cell type, peripheral rods, arises outside fruiting bodies . The pattern of expression of proteins in peripheral rods is different from that of either vegetatively growing cells or spores, and peripheral rods express a number of recognized developmental markers . In this report, we examine four aspects of the biology of peripheral rods: (i) the influence of nutrients on the proportion of peripheral rods in a population of developing cells, (ii) the capacity of peripheral rods to recapitulate development, (iii) the development of peripheral rods on conditioned medium, and (iv) the ability of peripheral rods to resume growth on low amounts of exogenously added nutrients . The results of these studies suggest that peripheral rods play a significant role in the life cycle of M . xanthus by allowing the exploitation of low amounts or transient influxes of nutrients without the investment of energy in spore germination . The differentiation of vegetatively growing cells into two cell types that differ significantly in biology, shape, and localization within the population has been incorporated into a model of the life cycle of M . xanthus.

J Bacteriol, 1991 Jun, 173(11), 3334 - 41
Analysis of Myxococcus xanthus cell types by two-dimensional polyacrylamide gel electrophoresis; O'Connor KA et al.; Myxococcus xanthus is a gram-negative, soil-dwelling bacterium that undergoes development in response to depletion of nutrients . Whereas most cells aggregate into multicellular mounds in which they differentiate into spores, 10 to 20% of the developing cells remain outside fruiting bodies as peripheral rods . We used two-dimensional polyacrylamide gel electrophoresis to analyze the global expression of polypeptides in cells taken from six stages in the life cycle: vegetatively growing cells, cells 15 h after the induction of development, peripheral rods, prespores (sonication-sensitive, aggregated cells), fruiting-body spores (sonication-resistant, aggregated cells) 96 h after the induction of development, and glycerol-induced spores 15 h after induction . Seven hundred sixty-one discrete sample spots (SSPs) were identified among the six gels . Comparisons among the samples revealed that each sample had some unique SSPs, ranging from 0.3% of the 15-h developing cell SSPs to 17.9% of 96-h peripheral rod SSPs . Sixty-eight SSPs were ubiquitously distributed, but the relative amounts of these SSPs varied among the samples . Statistical analyses of the distribution and relative quantities of the SSPs indicate that, within a confidence level of greater than 99.99%, peripheral rods are significantly different from vegetatively growing cells, 15-h developing cells, prespores, fruiting-body spores, and glycerol-induced spores . In fact, among the six samples studied, only 15-h developing cells and glycerol-induced spores were similar to each other within a confidence level of P greater than or equal to 0.05 . These results are consistent with the description of peripheral rods as a distinct developmental cell type.

J Bacteriol, 1991 Jun, 173(11), 3318 - 33
Development in Myxococcus xanthus involves differentiation into two cell types, peripheral rods and spores; O'Connor KA et al.; Myxococcus xanthus, a gram-negative bacterium, has a complex life cycle . In response to starvation, most cells in a population participate in the formation of multicellular aggregates (i.e., fruiting bodies) in which cells differentiate into spores . However, some cells do not enter aggregates . In this and the two accompanying reports, the biology and physiology of these nonaggregated cells is examined . A technique to separate aggregated cells from nonaggregated cells was developed; then differentiating cells at stages throughout the course of development were isolated . In this report we (i) describe peripheral rods, those cells which remain outside aggregates after aggregation has ceased in the rest of the population; (ii) document the occurrence of peripheral rods in several wild-type strains; and (iii) characterize the expression of developmentally regulated genes in both aggregated and nonaggregated cells . These studies have shown that myxobacterial hemagglutinin, protein S (Tps), protein S1 (Ops), protein C, and several phosphatase activities are expressed in cell-type-specific patterns . These data demonstrate that peripheral rods constitute a cell type distinct from either vegetatively growing cells or spores . The description of a second, late developmental cell type (in addition to spores) opens an entirely new line of investigation in M . xanthus, i.e., the regulation of the differentiation of vegetatively growing cells into two cell types that differ significantly in biology, shape, and localization within the population.

Mol Microbiol, 1991 Jun, 5(6), 1561 - 6
Transformation of Mycobacterium aurum and Mycobacterium smegmatis with the broad host-range gram-negative cosmid vector pJRD215; Hermans J et al.; The transformation of Mycobacterium aurum and Mycobacterium smegmatis with the Gram-negative RSF1010-derived cosmid pJRD215 is described . The plasmid is stably maintained in both species and the antibiotic resistance determinants for kanamycin and streptomycin are expressed . Southern blot analysis shows that rearrangements take place both in M . aurum and in M . smegmatis . The use of pJRD215 in mycobacterial cloning systems is discussed.

J Infect Dis, 1991 Jun, 163(6), 1256 - 66
Role of normal serum in the binding of lipopolysaccharide to IgG fractions from rabbit antisera to Escherichia coli J5 and other gram-negative bacteria; Warren HS et al.; Because lipopolysaccharide (LPS) bound to lipoprotein is less active than unbound LPS in multiple assay systems, the binding of radiolabeled LPS to lipoproteins in sera prepared from normal rabbits and rabbits made hyperimmune to Escherichia coli J5 were compared . LPS-lipoprotein binding in hyperimmune sera to E . coli J5 was not greater than that in normal serum as assessed by ultracentrifugation, but more LPS was precipitated from hyperimmune antisera than normal sera under conditions designed to precipitate LPS-lipoprotein complexes with calcium and dextran . Radiolabeled LPS was precipitated by delipidated antisera and fractions of IgG purified by anion exchange chromatography, but the precipitation was dependent on the presence of normal serum in the reaction mixture . These data suggest that a fluid-phase RIA done in the presence of normal serum may facilitate the detection of IgG in antisera raised to E . coli J5 that binds to heterologous smooth LPS.

Metabolism, 1991 Jun, 40(6), 585 - 93
Sepsis-induced increases in glucose uptake by macrophage-rich tissues persist during hypoglycemia; Lang CH et al.; The purpose of the present study was to determine how hypoglycemia alters glucose uptake by individual tissues and whether this response is altered by gram-negative infection . A hypermetabolic septic state was produced in catheterized rats by subcutaneous injections of live Escherichia coli . The next morning, animals were infused with saline, somatostatin to produce a euglycemic insulinopenic state (6 mmol/L glucose, 5 microU/mL insulin), or 3-mercaptopicolinate (3-MP) to inhibit gluconeogenesis and produce a hypoglycemic insulinopenic (4.5 or 2 mmol/L glucose, 5 microU/mL insulin) condition . After 140 minutes, {14C}2-deoxyglucose was injected intravenously (IV) to determine in vivo glucose uptake by individual tissues . Sepsis increased whole body glucose disposal (Rd) by 53% under basal euglycemic conditions and this increase resulted from an enhanced rate of glucose removal by liver, spleen, lung, ileum, and skin . Under euglycemic insulinopenic conditions, total glucose Rd decreased in both septic and nonseptic rats as a result of a decreased rate of glucose uptake by muscle . However, because the absolute rate of glucose uptake was still elevated by sepsis, the rate of non-insulin-mediated glucose uptake (NIMGU) was 46% higher in septic rats than in nonseptic animals . Severe hypoglycemia (2 mmol/L) produced a relative insulin deficiency and decreased whole body Rd in both septic and nonseptic animals by 53% to 58%, compared with euglycemic insulinopenic animals . The decrease in blood glucose decreased glucose uptake by all tissues examined, except brain and heart . However, sepsis still increased glucose uptake by liver, spleen, lung, ileum, and skin (25% to 90%), compared with hypoglycemic nonseptic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

J Gen Microbiol, 1991 Jun, 137 ( Pt 6), 1425 - 9
Characterization of a beta-lactamase produced by Pseudomonas paucimobilis; Corkill JE et al.; A novel beta-lactamase enzyme produced by a strain of Pseudomonas paucimobilis is described . The enzyme differs from other recorded beta-lactamases from Gram-negative aerobic bacteria . It was constitutive, and had the characteristics of a penicillinase . One single band of beta-lactamase activity at pI 4.6 was seen on iso-electric focusing . The enzyme had a molecular mass of 30 kDa . The beta-lactamase was strongly inhibited by tazobactam, sulbactam and clavulanic acid but not by the thiol residue inhibitors p-chloromercuribenzoate and p-chloromercuriphenylsulphonic acid, or by metallo-enzyme inhibitors . Plasmid DNA was not demonstrable, suggesting that the enzyme was chromosomally encoded.

Control Clin Trials, 1991 Jun, 12(3), 395 - 407
Termination of the Department of Veterans Affairs Cooperative Study of steroid therapy for systemic sepsis; Peduzzi P; The Department of Veterans Affairs Cooperative Study Program conducted a randomized, double-masked trial of steroid therapy versus placebo therapy for patients with systemic sepsis from 1983 to 1986 . Treatment was initiated as soon as sepsis was recognized and before results of cultures confirmed infection . The original hypothesis was to test the effect of therapy on short-term (14-day) mortality in patients with gram-negative bacteremia . Because therapy had to begin before culture results were available, all septic patients had to be enrolled . Consequently, the study was modified to evaluate therapy in all patients with sepsis, and by post-stratification in those with gram-negative bacteremia . Patient enrollment was planned to continue for 3.5 years to achieve a sample size of 276 patients . After 223 patients were randomized, 14-day mortalities were 22% in the placebo-treated group versus 21% in the steroid-treated group (p = 0.97) . In contrast, for the 51 patients with gram-negative bacteremia, mortalities were 27% placebo-treated versus 7% steroid-treated (p = 0.11) . The Data Monitoring Board recommended continuation of the trial to evaluate what appeared to be an emerging gram-negative trend, but the Cooperative Studies Evaluation Committee decided to end the trial 12 months early because of the lack of efficacy in all septic patients . The reasons for the proposed extension and for the termination of the trial are presented . The more general problem of evaluating a biologically important subgroup imbedded in a large clinical trial is also discussed.

Dtsch Med Wochenschr, 1991 May 17, 116(20), 768 - 71
{A protracted course in Cardiobacterium hominis endocarditis}; Zehnter E et al.; A 69-year-old man without previous cardiac disease was found over the last 9 months to have a markedly elevated erythrocyte sedimentation rate (ESR: 120 mm/1 . h), haemolytic anaemia (haemoglobin 8.2 g/dl, lactate dehydrogenase 304 U/l), markedly reduced exercise tolerance, backache and weight loss of 5 kg . Radiological, biochemical and endoscopic examinations failed to provide a diagnosis . Nine blood cultures grew, at normal body temperature, Cardiobacterium hominis, a rare Gram-negative organism which can cause endocarditis . Echocardiography revealed endocarditis of the aortic valve with regurgitation . Despite protracted and high-dosage antibiotics (4 times daily 10 million U penicillin G for 6 days, followed by four times 5 million U penicillin G for 6 days, followed by four times 5 million U daily for five weeks, and three times daily 60 mg gentamycin for 10 days), as well as treatment of extensive chronic parodontitis, anaemia, haemolysis and increased ESR have now persisted for over a year, with negative blood cultures . Immune-complex phenomena are thought to be the reason for the persistence of signs of infection.

Biochim Biophys Acta, 1991 May 2, 1089(1), 1 - 7
The alpha-ketoacid dehydrogenase complexes . Sequence similarity of rat pyruvate dehydrogenase with Escherichia coli and Azotobacter vinelandii alpha-ketoglutarate dehydrogenase; Matuda S et al.; The pyruvate dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex are multienzyme complexes consisting of three different enzymes . No significant similarity has been reported among the dehydrogenases which are component enzymes of these complexes, despite the presence of homology among the other component enzymes . Here we isolated cDNAs for the alpha and beta subunits of rat pyruvate dehydrogenase and they exhibited a significant similarity of the amino acid sequences among rat pyruvate dehydrogenase, 2-oxoisovalerate dehydrogenase (which is a dehydrogenase component of branched chain alpha-ketoacid dehydrogenase complex) and alpha-ketoglutarate dehydrogenase, suggesting that they have been derived from a common ancestral dehydrogenase . Our results suggested that the alpha and beta subunits of the pyruvate and 2-oxoisovalerate dehydrogenases have been derived by the cleavage of the alpha-ketoglutarate dehydrogenase . However, we could not find significant homology between rat pyruvate dehydrogenase and Gram-negative bacterial pyruvate dehydrogenase.

Am J Pathol, 1991 May, 138(5), 1097 - 101
Intratracheal injection of endotoxin and cytokines . II . Interleukin-6 and transforming growth factor beta inhibit acute inflammation; Ulich TR et al.; The nature of the endogenous mediators that down-regulate and curtail the exodus of neutrophils into local acute inflammatory sites is unknown . In the present report, interleukin-6 (IL-6) and transforming growth factor beta (TGF beta), members of a family of macrophage-derived proteins known as cytokines, are shown to inhibit significantly the acute neutrophilic exodus caused by an intratracheal injection of endotoxin (LPS), a proinflammatory component of the cell walls of gram-negative bacteria . Transforming growth factor beta (10 micrograms) and IL-6 (10 micrograms) coinjected intratracheally with LPS (10 micrograms) each inhibited the number of neutrophils in 6-hour bronchoalveolar lavage (BAL) specimens by approximately 50% . The intratracheal coinjection of IL-6, TGF beta, and LPS inhibited the LPS-induced neutrophilic inflammatory exodus by nearly 75% . Interleukin-6 also is shown to be endogenously upregulated within the lung after intratracheal challenge with endotoxin, providing evidence that IL-6 may represent an endogenous negative feedback mechanism to inhibit endotoxin-initiated cytokine-mediated acute inflammation . Interleukin-6 and TGF beta both strongly inhibited the quantity of TNF-alpha recovered in the BAL fluid of LPS-challenged rats, suggesting that downregulation of LPS-induced TNF-alpha production within the lung represents one mechanism whereby IL-6 and TGF beta exert an antiinflammatory action . Interleukin-6 and TGF beta represent novel pharmacologic and, probably, endogenous inhibitors of acute inflammation.

Arch Surg, 1991 May, 126(5), 591 - 7
Tumor necrosis factor and interleukin 1 appearance in experimental gram-negative septic shock . The effects of plasma exchange with albumin and plasma infusion; Busund R et al.; To study the effect of plasma removal vs plasma administration on the appearance of tumor necrosis factor (TNF) and interleukin 1 in septic shock, 24 anesthetized piglets were inoculated with live Escherichia coli . Plasma exchange with albumin was performed in one group . Fresh-frozen plasma was administered to a second group . A third group served as nontreated controls . Following plasma exchange, a reduction in both TNF and interleukin 1 levels occurred, whereas plasma infusion was followed by a decrease in TNF levels only . No significant differences were observed between the two treated groups with respect to survival or cardiovascular performance, with both being significantly enhanced compared with the controls . High levels of TNF and interleukin 1 correlated with depressed cardiovascular performance in the early phase of the shock . Our results confirm the important role of TNF and interleukin 1 as early mediators of septic shock . However, the benefit of reducing cytokine activity in later stages of septicemia seems to be dubious.

Vopr Med Khim, 1991 May-Jun, 37(3), 26 - 8
{Functional state of the liver during development of extrahepatic cholestasis and during use of enterosorption}; Grin'ko IV et al.; Use of enterosorption during the first week of extrahepatic cholestasis in rats led to decrease of disorders in functional state of liver tissue and its subcellular organelles as well as of accumulation of toxic substances in organism . The main effect of enterosorption appears to be binding of Gram-negative bacteria endotoxin in intestine.

J Vet Intern Med, 1991 May-Jun, 5(3), 167 - 81
Endotoxemia in horses . A review of cellular and humoral mediators involved in its pathogenesis; Morris DD; Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia . Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues . Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease . Macrophages become highly activated for enhanced secretory, phagocytic and cidal functions by LPS . Macrophage-derived cytokines are responsible for many of the pathophysiologic consequences of endotoxemia . The arachidonic acid metabolites, prostacyclin and thromboxane A2 likely mediate early hemodynamic dysfunction and the leukotrienes may potentiate tissue ischemia during endotoxemia . Interleukin 1 (IL-1) induces fever and is responsible for the inflammatory cascade, which constitutes the acute phase response . Tumor necrosis factor (TNF), an important proximal mediator of the effects of LPS, acts to initiate events and formation of other molecules that affect shock and tissue injury . Systemic administration of TNF produces most of the physiologic derangements that are associated with endotoxemia and antibodies that are directed against TNF significantly reduce LPS-induced mortality in experimental animals . In response to endotoxins, mononuclear phagocytes express thromboplastin-like procoagulant activity (PCA), which initiates microvascular thrombosis . Both IL-1 and TNF induce PCA expression, creating a positive feedback loop for LPS-induced coagulopathy . A macrophage-derived platelet activating factor contributes to coagulation dysfunction and further stimulates arachidonic acid metabolism . The ultimate consequences of endotoxemia are multiple system organ failure and death . The numerous feedback loops and intertwining cascades of mediators during endotoxemia defy simplistic methods of treatment . The optimal therapy likely involves methods to alter the generation of inflammatory mediators by mononuclear phagocytes.

Clin Pharmacokinet, 1991 May, 20(5), 374 - 88
An updated comparison of drug dosing methods . Part III: Aminoglycoside antibiotics; Erdman SM et al.; Aminoglycoside antibiotics continue to be useful for the treatment of Gram-negative infections . Available dosing methods include predictive algorithms and nomograms, pharmacokinetics-based dosing methods, and methods that incorporate Bayesian forecasting . The individualised Sawchuk-Zaske and Bayesian methods have been extensively evaluated since the previous review in the Journal . Both methods continue to be rapid and accurate means of individualising dosage requirements for patients with diverse pharmacokinetic profiles . The predictive performance of the Bayesian method can be further enhanced when population-based parameters reflect the patient population being monitored . There are now several cost-effectiveness studies that demonstrate that pharmacokinetic dosing services for aminoglycosides result in cost savings, better therapeutic concentrations, fewer toxic serum concentrations, and shorter mean durations of hospital stay and aminoglycoside therapy . Further studies are needed for cost-effectiveness and comparison of various dosing methods in paediatric and neonatal patients.

Res Vet Sci, 1991 May, 50(3), 315 - 8
Serum cortisol changes in heifers induced by lipid X: a monosaccharide precursor in the biosynthesis of Gram-negative endotoxin; Peter AT et al.; An experiment was conducted to measure the changes in serum cortisol and luteinising hormone (LH) concentrations in heifers during the luteal phase of the oestrous cycle after the administration of lipid X and Gram-negative endotoxin . Nine heifers whose oestrous cycles were synchronised with prostaglandin F2 alpha were assigned at random on day 10 after the second prostaglandin injection to one of the following groups . Group 1 heifers (n = 3) received 5 micrograms kg-1 bodyweight of Escherichia coli endotoxin as an intrauterine infusion and one hour later received an intravenous injection of lipid X (5 micrograms kg-1 bodyweight) . The treatment was reversed in group 2 heifers (n = 3), endotoxin was administered one hour after the lipid X treatment . Group 3 heifers (n = 3) received endotoxin infusion and lipid X treatment at the same time . Similar dosages and routes of administration were used in all the groups for lipid X and endotoxin treatments . Blood samples were collected once every 15 minutes for seven hours, beginning once hour before and six hours after the initial treatment . In group 1 heifers there was a fourfold increase in serum cortisol concentrations within 30 minutes after both the treatments (from 6.5 to 24.6 ng ml-1 and from 7.3 to 29.5 ng ml-1 respectively) . In group 2 heifers the cortisol concentrations increased from the baseline concentrations of 7.2 to 33.2 ng ml-1 within 30 minutes after lipid X treatment and remained at 22.5 ng ml-1 during endotoxin treatment . There was a further increase in cortisol concentrations (28.9 ng ml-1) after the endotoxin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Pediatr Otorhinolaryngol, 1991 May, 21(3), 259 - 62
Branchial anomaly in a newborn presenting as stridor; Morrish TN et al.; A male patient presented at day 3 of life with a small anterior neck mass and mild intermittent upper airway obstruction . Despite intravenous antibiotics, the patient rapidly progressed to impending airway obstruction requiring surgical intervention . The clinical, radiographic, and histologic findings of this extremely rare case of a third branchial anomaly will be presented . The embryologic basis for the connection to the aerodigestive tract and the access provided to gram negative enteric organisms in newborns will be discussed.

Rev Infect Dis, 1991 May-Jun, 13(3), 397 - 404
Ceftazidime plus amikacin versus ceftazidime plus vancomycin as empiric therapy in febrile neutropenic children with cancer; Viscoli C et al.; Two antibiotic regimens, ceftazidime plus amikacin and ceftazidime plus vancomycin, were compared in a prospective, randomized clinical trial as empiric therapy in febrile granulocytopenic children with cancer . The rate of response was similar in the two groups (66% vs . 77%) . The prevalence of secondary gram-negative bacteremia was higher--but not significantly higher--in the group receiving vancomycin . Adverse reactions also occurred more often in the latter group (35% vs . 4%) . Mortality did not differ significantly in the two groups . Adjustment for independent predictors of response to treatment by means of multivariate analysis confirmed the lack of any remarkable difference between the responses to the two regimens . We conclude that the use of vancomycin instead of amikacin in combination with ceftazidime does not significantly improve the outcome of treatment of fever and infection in granulocytopenic children with cancer and that the use of vancomycin is associated with an increased frequency of both secondary infections due to gram-negative bacteria and adverse reactions.

JPEN J Parenter Enteral Nutr, 1991 May-Jun, 15(3), 307 - 12
Dietary manipulation of methotrexate-induced enterocolitis; Shou J et al.; Administration of chemotherapy is limited by host toxicity, which is often manifested by severe enterocolitis . This study evaluated the effects of a liquid, elemental, chemically defined diet (ED) supplemented with 2% glutamine (Glu-ED) compared with a polypeptide diet (PPD) on the morbidity and mortality after methotrexate (MTX) administration . Fischer 344 rats (n = 80) were fed either a regular rat chow diet (RD), a 2% glycine supplemented elemental diet (Gly-ED), a 2% glutamine-supplemented elemental diet (GLU-ED), and a glycine-supplemented polypeptide diet(Gly-PPD) for 7 days prior to administration of MTX (20 mg/kg, ip) . After 72 hours, eight rats per group were killed; portal vein and vena cava blood, mesenteric lymph nodes (MLN), liver, small intestine, and cecum were sampled for bacterial culture . Remaining animals were followed to calculate survival . One hundred percent of the Gly-PPD and 25% of the Glu-ED animals survived compared with 0% of the Gly-ED animals . Our data showed that ED resulted in an increased quantity of intestinal Gram-negative bacteria and diminished intestinal mucosal height and mucosal DNA/protein content . The polypeptide diet prevented intestinal mucosal atrophy, avoided MTX-induced enterocolitis and significantly improved animal survival compared with an elemental diet with or without glutamine supplementation.

J Antimicrob Chemother, 1991 May, 27 Suppl C, 121 - 8
Efficacy and safety of amikacin in systemic infections when given as a single daily dose or in two divided doses . Scandinavian Amikacin Once Daily Study Group; Maller R et al.; Two hundred and twenty patients with serious infections verified or suspected to be of Gram-negative aetiology were treated in an open randomized comparative multicentre trial with amikacin 15 mg/kg/day given either as a single dose or in two divided doses at 12-h intervals . Amikacin was administered as a short-term iv infusion . When additional therapy was considered necessary piperacillin or ampicillin was recommended . The trial continues and an interim report on data from the 12 participating Scandinavian hospitals is presented . One hundred and forty-four patients have been evaluated for efficacy and 213 patients for safety . There were no significant differences between the two dosage regimens regarding efficacy and safety . A satisfactory clinical response was recorded in 129 (90%) of the evaluable patients . One serious adverse reaction was seen in a patient in the once-daily group . This was ototoxicity which was superimposed on a long standing hearing defect possibly caused by previous streptomycin therapy.

Antimicrob Agents Chemother, 1991 May, 35(5), 983 - 5
Modulation of the intestinal flora of mice by treatment with aztreonam and tigemonam; van Ogtrop ML et al.; Oral and parenteral administration of aztreonam and oral administration of tigemonam to conventional mice caused a decrease in the number of aerobic gram-negative rods in the feces . Oral treatment with high doses of aztreonam (greater than or equal to 25 mg/kg/day) and tigemonam (100 mg/kg/day) adversely influenced colonization resistance, whereas oral treatment with lower doses of the monobactams or parenteral treatment with aztreonam did not.

Bull Tokyo Dent Coll, 1991 May, 32(2), 63 - 70
Clinical and microbiological study of local minocycline delivery (Periocline) following scaling and root planing in recurrent periodontal pockets; Nakagawa T et al.; This study was designed to evaluate the clinical and microbiological effects of local administration of 2% minocycline-HCl ointment (Periocline) combined with scaling and root planing in recurrent periodontal pockets . Thirty-three sites were selected for this examination . The sites had probing depths greater than 5 mm and loss of attachment greater than 2 mm within the previous 3 months . They were assigned as test (22 sites) or control sites (11 sites) . After meticulous scaling (SC) and root planing (RP), Periocline was delivered into the periodontal pockets of test sites: control sites were irrigated with biological saline following SC/RP . Administration of Periocline or irrigation with saline was performed once a week for 4 consecutive weeks . The effects on clinical conditions including probing pocket depth, clinical attachment level, and bleeding on probing were evaluated at baseline, 2, 4, 8, and 12 weeks . Microbiological examinations consisting of darkfield microscopic study and culture were performed at baseline, 4, and 12 weeks . Clinical conditions improved in both groups following treatment; significantly better improvements were obtained in the test group . Microbiological study revealed that Periocline effectively eliminated periodontopathic gram-negative bacteria . These results indicated that a combination of SC/RP with local administration of 2% minocycline for recurrent periodontal pockets brought about more satisfactory results than conventional SC/RP.

J Gen Microbiol, 1991 May, 137 ( Pt 5), 1215 - 22
The use of 16S ribosomal RNA analyses to investigate the phylogeny of the family Legionellaceae; Fry NK et al.; The 16S ribosomal RNA sequences of Legionella pneumophila, L . erythra, L . hackeliae, L . spiritensis, L . longbeachae, L . bozemanii (Fluoribacter bozemanae) and L . micdadei (Tatlockia micdadei) were determined using reverse transcriptase . The sequences were compared with published sequences for Gram-negative bacteria and phylogenetic trees were constructed . The data confirm previous work which showed that the family Legionellaceae forms a monophyletic subgroup within the gamma subdivision of the Proteobacteria . The data show that all of the legionellae studied are highly related (greater than 95%) on the basis of 16S rRNA sequences and do not support the division of the family Legionellaceae into three genera.

J Exp Med, 1991 May 1, 173(5), 1281 - 6
Activation of the adhesive capacity of CR3 on neutrophils by endotoxin: dependence on lipopolysaccharide binding protein and CD14; Wright SD et al.; Tumor necrosis factor alpha, granulocyte colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, and formyl peptide were each found to cause a twofold increase in expression of CD14 on the surface of polymorphonuclear leukocytes (PMN) . Upregulation of CD14 was complete by 20 min and thus appeared to result from expression of preformed stores of protein . The CD14 on the surface of PMN was shown to serve two biological functions . It bound particles coated with complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP) . This binding activity was enhanced by agonists that upregulated CD14 expression and may serve in the clearance of Gram-negative bacteria opsonized with LBP . Interaction of CD14 with LPS in the presence of LBP or serum also caused a dramatic, transient increase in the adhesive activity of CR3 (CD11b/CD18) on PMN . Enhanced activity of CR3 and other members of the CD11/CD18 family underlies many of the known physiological responses of PMN to LPS and may be a central feature of the in vivo responses of PMN to endotoxin.

Carbohydr Res, 1991 Apr 2, 211(1), 91 - 102
L-guluronan-specific alginate lyase from a marine bacterium associated with Sargassum; Brown BJ et al.; The major extracellular alginate lyase activities secreted by a Gram-negative, facultative bacterium associated with actively growing Sargassum fluitans have been resolved an examined for substrate specificity . A fraction excluded from Sephadex G-75 was equally active toward (1----4)-beta-D-mannuronan, (1----4)-alpha-L-guluronan, and alginate with the formation of di- and tri-saccharides as apparent limit products and oligo-saccharides indicative of an endolytic mechanism . A second fraction which was included during G-75 filtration was inactive toward D-mannuronan and 4 times more active toward L-guluronan than native alginate . Proton magnetic resonance spectrometry identified the primary product of this enzyme as O-(4-deoxy-alpha-L-erythro-hex-4-enopyranosyluronic acid)-(1----4)-O-(alpha-L-gulopyranosyluronic acid)-(1----4)-O-alpha-L-gulopyranuronic acid . The L-guluronan-specific enzyme requires 0.5 M NaCl for maximal activity and has been purified as a monomeric protein having an apparent molecular mass of 38 kD and an approximate pI of 4.5 . The predominant formation of trisaccharide over the course of a reaction showed a primarily exolytic mechanism, indicating an enzyme activity unique from any previously reported.

Arch Mal Coeur Vaiss, 1991 Apr, 84(4), 569 - 72
{Colonic angiodysplasia with chronic digestive hemorrhage cured after valvular replacement for aortic valve stenosis}; Obadia JF et al.; Aortic stenosis is found in 15 to 25% of patients with gastrointestinal angiodysplasia . The usual treatment for haemorrhagic angiodysplasia associated with aortic stenosis is the same as for other types of gastrointestinal angiodysplasias: segmental intestinal resection, electrocoagulation and laser photocoagulation . The authors report the case of a 73 year old woman with a long history of gastro-intestinal bleeding and chronic anaemia requiring a number of hospital admissions for blood transfusions . The cause of this bleeding remained obscure for many years, as it was initially thought to be due to portal hypertension complicating cyrrhosis and a surgical porto-caval shunt was performed . Later, angiodysplasia of the colon was recognised and a segmental colonic resection was performed . These two surgical procedures had no effect on the chronic bleeding and finally the patient was referred for a gram negative endocarditis complicating aortic stenosis, previously considered to be non-surgical . After controlling the infection, the patient was sent for surgery of the aortic valve disease with mitral regurgitation in view of progressive degradation of left ventricular function . A double valve replacement with bioprostheses was undertaken with no complication . Finally, three years now after valve replacement, no further bleeding has occurred and control colonoscopy is normal . In the light of this case and a review of the literature of about 30 similar cases, the physiopathology and management of these patients is discussed with respect to the choice of valve prosthesis and the attitude to anticoagulant therapy . These observations suggest that in the presence of valvular heart disease at a surgical stage associated to an angiodysplasia, it is preferable to propose valve surgery to start with . Gastro-intestinal surgery is only indicated if haemorrhage persists after a period of observation.

Kidney Int, 1991 Apr, 39(4), 618 - 23
Role of neutrophil derived oxidants and elastase in lipopolysaccharide-mediated renal injury; Linas SL et al.; Gram-negative bacterial sepsis is frequently associated with acute renal failure but the specific effects of lipopolysaccharide (LPS) and other bacterial products on kidney function are not known . Since either LPS or formyl-methionyl-leucyl-phenylalanine (FMLP)--a chemotactic peptide from bacterial cell walls--activate neutrophils (PMN) to release a number of potentially toxic factors in vitro, we determined the effect of adding PMN with LPS and/or FMLP to isolated perfused rat kidneys . Isolated rat kidneys perfused with LPS alone or LPS and normal PMN had normal glomerular filtration rates (GFR) and tubular Na reabsorption (TNa) . Kidneys perfused with FMLP alone or FMLP and normal PMN also had normal GFR and TNa . In contrast, addition of PMN with both FMLP and LPS caused progressive renal dysfunction . For example, after 60 minutes of perfusion, GFR was reduced from 610 +/- 31 to 147 +/- 17 microliters/min/g and TNa from 97 +/- 1 to 72 +/- 2%, both P less than 0.01 . Perfusion with the O2 metabolite scavengers catalase or dimethylthiourea afforded no protection while perfusion with the neutrophil elastase inhibitor Eglin C conferred substantial, but not complete, protection: GFR 492 +/- 34 microliters/min/g; TNa 91 +/- 3% . However, perfusion with both Eglin C and catalase completely prevented the toxic effects of LPS and FMLP-treated PMN on renal function . We conclude that in isolated kidneys, 1) the toxic effects of LPS requires FMLP-treated PMN and that 2) LPS and FMLP treated PMN cause progressive renal injury which is mediated by both O2 metabolites and neutrophil elastase.

Masui, 1991 Apr, 40(4), 605 - 10
{Evaluation of the dose of endotoxin to produce endotoxin shock models in dogs}; Yoshizawa M et al.; Intravenous bolus administration of purified endotoxin (ET) is one of the most popular methods of producing experimental ET shock . In an attempt to evaluate the dose of ET in these experimental models, the kinetics of ET was assessed in various doses (1-0.002 mg.kg-1), and dose response study was performed, measuring chronological changes in hemodynamic (mean arterial pressure & cardiac output) and hematological (leucocyte & platelet counts) parameters . It was demonstrated that plasma ET concentrations were sustained extraordinarily high (greater than 5000 pg.ml-1) in doses of 0.2-1 mg.kg-1 during the observation period of several hours, while they were measurable in doses of 0.02 and 0.002 mg.kg-1, showing a biphasic decrease pattern after ET administration . In particular, plasma ET levels of low dose group (0.002 mg.kg-1) were similar to those of clinical gram negative septic patients . We conclude that the empirically used ET doses of more than 1 mg.kg-1 produce extremely severe endotoxemia and that milder degree of ET shock models produced by low dose of ET (0.002 mg.kg-1) would be more applicable for a pathophysiological study of ET shock.

Gut, 1991 Apr, 32(4), 450 - 1
Septicaemia after colonoscopy in patients with cirrhosis; Thornton JR et al.; Two patients with ulcerative colitis and chronic active hepatitis with cirrhosis, who developed Gram negative septicaemia after colonoscopy are described . These and two similar reported cases indicate that giving prophylactic antibiotics to patients with cirrhosis undergoing colonoscopy should be considered, particularly when the cirrhosis is advanced.

J Exp Med, 1991 Apr 1, 173(4), 1021 - 4
Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents; Martich GD et al.; Interleukin 8 (IL-8), a potent activator of neutrophils, may be important in the early host response to serious Gram-negative infections . IL-8 was measured with other acute phase cytokines (tumor necrosis factor alpha {TNF-alpha}, IL-6 and IL-1 beta) in 25 normal humans randomized to receive either intravenous endotoxin alone or endotoxin after oral administration of ibuprofen or pentoxifylline, agents that alter some of the inflammatory responses induced by endotoxin in vitro . TNF immunoreactivity was maximum at 1.5 h, and total TNF (area under the curve) was 4.2- and 4.5-fold greater in subjects given endotoxin/ibuprofen compared to subjects given endotoxin alone (p = 0.026) or endotoxin/pentoxifylline (p = 0.004), respectively . IL-6 levels were maximum at 2-3 h and did not differ among the three groups . No IL-1 beta was detected in any subject . IL-8 levels peaked at 2 h in subjects given either endotoxin alone or endotoxin/pentoxifylline, falling towards baseline by 5 h . Subjects given endotoxin/ibuprofen had a more sustained rise in IL-8 with peak levels 2.8- and 2.5-fold higher at 3 h compared to endotoxin alone (p = 0.048) or endotoxin/pentoxifylline (p = 0.023), respectively . Differences in total IL-8 release among groups approached statistical significance (ANOVA, p = 0.07) . This trend reflected the increased release of IL-8 by the subjects receiving ibuprofen compared to pentoxifylline (1.9-fold higher; p = 0.024) . This suggests that cyclooxygenase products may provide important negative feedback loops for cytokine production in vivo . Increases in circulating IL-8 are part of the acute inflammatory response of humans to endotoxin . Altered cytokine responses caused by antiinflammatory therapy may have important implications for both host defense and injury during septicemia.

Infect Immun, 1991 Apr, 59(4), 1394 - 401
Regulation of leukotoxin in leukotoxic and nonleukotoxic strains of Actinobacillus actinomycetemcomitans; Spitznagel J Jr et al.; Actinobacillus actinomycetemcomitans is a gram-negative bacterium that has been implicated in the etiology of several forms of periodontitis, especially localized juvenile periodontitis . A potent leukotoxin (Lkt) is produced by most A . actinomycetemcomitans isolates from patients with periodontal disease, but some isolates are leukotoxin nonproducing (Lkt-) . The molecular bases for the differences in leukotoxin expression are being explored to clarify the role of leukotoxin in pathogenesis . We have previously cloned the leukotoxin structural gene, lktA, from the leukotoxin-producing (Lkt+) strain JP2 and have shown that it is linked to three other genes, lktB, lktC, and lktD, whose gene products are thought to be required for activation and localization of the leukotoxin . These genes have now been used in Southern blot analysis to demonstrate that Lkt- strains, like Lkt+ strains, contain all four genes of the lkt gene cluster . While restriction fragment length polymorphisms were detected, they did not correlate with toxin phenotype . RNA blot analysis demonstrated that Lkt+ strains produced two transcripts, one 9.3 kb in length and the other 4.3 kb . They encode lktCABD and lktCA . respectively . Lkt- strains contained significantly lower levels of the 4.3-kb transcript with no discernible 9.3-kb message . The leukotoxic activity of the A . actinomycetemcomitans strains, measured by chromium release assays, correlated with the lkt RNA content . Therefore, a major component of leukotoxin regulation is at the level of RNA transcription or stability . Interestingly, the lkt RNAs in JP2 are regulated during growth phase, being greatly reduced in cells approaching stationary phase . Thus, the regulation of lkt RNA can be affected by both genotype and environment.

DICP, 1991 Apr, 25(4), 357 - 9
In vivo inactivation of tobramycin by piperacillin; Uber WE et al.; In vivo inactivation of aminoglycosides by antipseudomonal penicillins in patients with renal failure can be a significant problem when these drugs are used together in certain gram-negative infections . Our article illustrates the possible magnitude of this interaction and the resultant effect on aminoglycoside pharmacokinetic parameters . Penicillin concentrations remain relatively unaffected by this interaction . This article stresses the need for close monitoring of aminoglycoside concentrations when combined with antipseudomonal penicillins in this patient population.

J Chemother, 1991 Apr, 3(2), 98 - 100
Aztreonam biliary excretion in bile duct ligated jaundiced rats; Rulli F et al.; An experimental study was undertaken to assess aztreonam biliary concentrations in bile duct ligated jaundiced rats . The study proved that aztreonam biliary concentrations are sufficient to inhibit Gram-negative bacteria within the first and the second hour after antibiotic administration . The experimental model suggests that clinical conditions such as lithiasis or neoplasms of the biliary tree should not totally inhibit the antibiotic excretion.

J Gen Microbiol, 1991 Apr, 137 ( Pt 4), 905 - 11
Characterization and comparative bactericidal activity of monoclonal antibodies to Bordetella pertussis lipo-oligosaccharide A; Archambault D et al.; Spleen cells from mice immunized with a Bordetella pertussis N-lauroyl sarcosine membrane extract (SME) were used to generate hybridoma cells lines producing monoclonal antibodies (mAbs) . Seven mAbs were shown to be specific to B . pertussis lipo-oligosaccharide (LOS) by immunoblotting of SME or purified LOS following SDS-PAGE . All mAbs reacted with the B . pertussis Tohama I strain of the LOS AB phenotype, and did not react with the atypical variant strain 134 of the LOS B phenotype . The immune reactivity of the mAbs was retained after treatment of SME with proteinase K and was lost after sodium periodate treatment . No cross-reactivity was observed with the mAbs when tested against B . parapertussis and other Gram-negative bacteria . However, all mAbs reacted with B . bronchiseptica . Binding assays with live B . pertussis cells demonstrated that mAbs strongly reacted with cell surface exposed antigenic determinants . High bacterial cell lytic capability was observed for five of these mAbs . Concentrations between 0.22 and 2.2 micrograms mAb ml-1 (0.1 and 1 microgram per 450 microliter assay) purified by protein A were required to kill at least 50% of the bacteria . Competition immunoassays with biotinylated antibodies showed that the bacteriolytic and non-bacteriolytic mAbs were directed to different epitopes of the B . pertussis LOS A.

Can J Surg, 1991 Apr, 34(2), 137 - 43
Acute pancreatitis--30 years' experience at a teaching hospital; Amurawaiye EO et al.; Advances in medical technology and knowledge have influenced morbidity and mortality in surgically treated diseases . The authors have compiled four consecutive retrospective studies of demography, morbidity and mortality of patients with acute pancreatitis to summarize the experience from 1956 to 1985 at the Montreal General Hospital with 629 patients . The death rate has remained unchanged . Hypotension, gastrointestinal bleeding and respiratory failure have assumed lesser roles as major complicating factors . Renal failure and gram-negative aerobic pancreatic sepsis are the common causes of death . The last two reviews revealed that surgical debridement and drainage combined with appropriate biliary procedures salvaged two-thirds of the patients with sepsis . Deteriorating nutritional status, heralded by a fall of serum albumin level below 30 g/L, is associated with a poor prognosis . Interval cholecystectomy in patients with mild biliary tract pancreatitis is associated with a low death rate (0.01%).

J Infect Dis, 1991 Apr, 163(4), 762 - 8
Antibodies to core lipopolysaccharide determinants: absence of cross-reactivity with heterologous lipopolysaccharides; Heumann D et al.; Using monoclonal antibodies directed against defined epitopes of endotoxin core, this study demonstrated that the presentation of lipopolysaccharide (LPS) to antibodies is critical for measuring the specific binding of antibodies to LPS structures . False cross-reactive reactions apparently were observed when free core LPS or lipid A were used as antigens in ELISA, whereas coating with complexes of high-density lipoproteins with core LPS increased both the sensitivity and the specificity of the test compared with coating with free core LPS, so that nonspecific binding of antibodies was largely avoided . Using this technique, it was not possible to find broadly cross-reactive core LPS antibodies after immunization of rabbits and humans with rough mutants of gram-negative bacteria . These observations underscore the need for careful evaluation of the potential for cross-reactivity of antisera and of monoclonal antibodies directed against endotoxin core.

Lab Anim Sci, 1991 Apr, 41(2), 146 - 50
Infusion-related sepsis in dogs undergoing acute cardiopulmonary surgery; Slattum MM et al.; During acute cardiopulmonary studies, 33 of 170 (19.4%) dogs developed uncontrollable acidosis accompanied by varying degrees of diarrhea and hypotension . Affected dogs had evidence of gram-negative bacteremia and septic shock . Intravenously administered fluids were contaminated with gram-negative bacteria . Since the experimental procedure entailed nonsurvival surgery, aseptic techniques were not employed . Although aseptic surgical techniques are to be used in animals undergoing survival surgery, such techniques also may be warranted in non-survival surgeries.

Resuscitation, 1991 Apr, 21(2-3), 137 - 80
The cell in shock: the origin of multiple organ failure; Schlag G et al.; The immediate organ damage seen after multiple trauma and in shock is a typical example of non-bacterial inflammation triggered by activation of various mediators of both the humoral and cellular systems . Anaphylatoxins and the low-flow syndrome during the shock phase account for increased PMN* margination, which in turn causes pulmonary leukostasis and may provoke massive mediator release by PMN (oxygen radicals, proteinases, eicosanoids, PAF etc) . This probably leads to severe endothelial cell damage, especially in the lung . Adherence of PMN to the endothelium appears to create the micro-environment where high concentrations of proteolytic enzymes and reactive oxygen radicals exert a deleterious effect on the cell membrane . Endothelial cell membrane injury leads to increased vascular permeability and cell edema . The development of the 'organ in shock' may require a few hours and initially cause minor or no functional impairment at all . Only when shock is severe is there early organ failure, which in this stage may still be an expression of non-bacterial inflammation . Numerous studies have reported the existence of shock-induced cardiodepressant substances in association with various forms of circulatory shock . We have determined a net negative inotropic effect of the low-molecular-weight plasma fraction in severe hypovolemic-traumatic shock and have isolated a cardiodepressant factor (CDF), which by blockade of the calcium inward current has a negative inotropic a chronotropic effect . The intestine as a shock organ appears to range first among the organs involved . The translocation of bacteria from the intestinal tract, the 'intestine in shock' represents the trigger reaction that eventually leads from the 'organ in shock', early organ failure to late (septic) organ failure . Here the most prominent factor is endotoxin (LPS) as a basic mediator of gram-negative bacteria, which also triggers the activation of humoral and cellular systems . The posttraumatic hyperdynamic phase commonly starts on days 3-5 and is mainly caused by bacteremia and/or endotoxemia . Macrophages have a major impact on the late phase of organ failure . At present, the most prominent cellular mediator of the lethal effect of endotoxin is thought to be cachectin, which is identical with the tumor necrotising factor (TNF) . TNF is secreted by monocytes/macrophages (MO/MA) in response to LPS . Via macrophage derived cytokines and by LPS there is activation of endothelial cells, with increased adhesiveness for PMN . Both due to this increased adhesiveness and the presence of LPS and cytokines, PMN undergo massive activation, which causes mediator release and tissue damage.(ABSTRACT TRUNCATED AT 400 WORDS)

Nature, 1991 Mar 14, 350(6314), 167 - 70
Structural architecture of an outer membrane channel as determined by electron crystallography; Jap BK et al.; Porins are a family of membrane channels commonly found in the outer membranes of Gram-negative bacteria where they serve as diffusional pathways for waste products, nutrients and antibiotics, and can also be receptors for bacteriophages . Porin channels have been shown in vitro to be voltage-gated . They can exhibit slight selectivities for certain solutes; for example PhoE porin has some selectivity for anionic and phosphate-containing compounds . Unlike many known membrane proteins which often contain long stretches of hydrophobic segments that are believed to traverse the membrane in a helical conformation, porins are found to have charged residues distributed almost uniformly along their primary sequences and have most of their secondary structure in a beta-sheet conformation . We have made crystalline patches of PhoE porin embedded in a lipid bilayer and have used these to determine the structure of PhoE porin by electron crystallography to a resolution of 6A . The basic structure consists of a trimer of elliptically shaped, cylindrical walls of beta sheet . Each cylinder has an inner lining, formed by parts of the polypeptide, that defines the channel size . The structure provides a clue as to how deletions of segments of polypeptide, which are found in certain mutants, can result in an actual increase in the channel size.

Bone Marrow Transplant, 1991 Mar, 7(3), 227 - 34
Prevention of cytomegalovirus infection following bone marrow transplantation: a randomized trial of blood product screening; Miller WJ et al.; From 1983 to 1987, cytomegalovirus seronegative allogeneic bone marrow recipients were randomized to receive screened cytomegalovirus (CMV) seronegative or unscreened blood products and 125 patients were available for analysis . CMV infection occurred in 18% of patients in the screened versus 38% in the unscreened blood product group . However, only two of 64 patients in the screened group and seven of 61 in the unscreened group developed culture or biopsy-proven CMV infections . Bone marrow donor CMV seropositivity was associated with an increased risk of developing CMV infection (21% with seronegative and 46% with seropositive donor), and CMV infection was not prevented by blood product screening if the bone marrow donor was sero = positive (62% for screened, 42% for unscreened group, p = 0.80) . One year survival censored for relapse was 52% in the screened group versus 68% in the unscreened group (p = 0.08) . Gram negative bacteremia complicated bone marrow transplantation (BMT) in 35% of patients receiving screened and 15% of those receiving unscreened blood products (p = 0.02) . Relapse did not differ in the screened and unscreened groups . By multivariate analysis, high risk disease (p = 0.0002), CMV infection (p = 0.004), screened blood products group (p = 0.011), recipient age greater than 17 (p = 0.027), chronic graft-versus-host disease (p = 0.014) and gram negative bacteremia (p = 0.004) independently had a negative influence on survival . We conclude that blood product screening was effective in preventing CMV infections following BMT if both the recipient and bone marrow donor were CMV seronegative.(ABSTRACT TRUNCATED AT 250 WORDS)

J Mol Biol, 1991 Mar 5, 218(1), 141 - 8
Carboxy-terminal phenylalanine is essential for the correct assembly of a bacterial outer membrane protein; Struyve M et al.; Bacterial outer membrane proteins are supposed to span the membrane repeatedly, mostly in the form of amphipathic beta-sheets . The last ten C-terminal amino acid residues of PhoE protein are supposed to form such a membrane-spanning segment . Deletion of this segment completely prevents incorporation into the outer membrane . Comparison of the last ten amino acid residues of other outer membrane proteins from different Gram-negative bacteria revealed the presence of a potential amphipathic beta-sheet with hydrophobic residues at positions 1 (Phe), 3 (preferentially Tyr), 5, 7 and 9 from the C terminus, in the vast majority of these proteins . Since such sequences were not detected at the C termini of periplasmic proteins, it appears to be possible to discriminate between the majority of outer membrane proteins and periplasmic proteins on the basis of sequence data . The highly conserved phenylalanine at the C termini of outer membrane proteins suggests an important function for this amino acid in assembly into the outer membrane . Site-directed mutagenesis was applied to study the role of the C-terminal Phe in PhoE protein assembly . All mutant proteins were correctly incorporated into the outer membrane to some extent, but the efficiency of the process was severely affected . It appears that both the hydrophobicity and the aromatic nature of Phe are of importance.

Circ Shock, 1991 Mar, 33(3), 127 - 34
Lethal E . coli septic shock is prevented by blocking tissue factor with monoclonal antibody; Taylor FB Jr et al.; Gram-negative bacteremia poses a major health problem, causing one-half of cases of lethal septic shock acquired during hospitalization . Bacterial lipopolysaccharide (LPS) and the inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), have been shown to be essential mediators of septic shock . Among the effects of these mediators is a coagulopathy that may be triggered by induced expression of tissue factor (TF) on macrophages and endothelial cells . We now report that 500 micrograms/kg of either immunoglobulin G (IgG) or Fab fragments of a monoclonal antibody against TF administered to baboons as a pretreatment attenuates the coagulopathy and protects against LD100 Escherichia coli . This study provides direct evidence of an essential effector role for TF in septic shock.

Rev Infect Dis, 1991 Mar-Apr, 13(2), 201 - 6
Leptotrichia buccalis bacteremia in patients with cancer: report of four cases and review; Weinberger M et al.; Leptotrichia buccalis, an anaerobic gram-negative rod, is part of the normal oral flora and has rarely been isolated from clinical material . We describe four patients with neutropenia and progressive malignancy who had symptomatic L . buccalis bacteremia, and we review an additional four cases from the literature . The mean age of the patients was 31 years (range, 7-73 years), with an equal number of males and females . The number of positive blood cultures in each case ranged from one to four (mean, two); these cultures became positive after 48-120 hours (median, 54 hours) . All tested isolates were sensitive to the beta-lactam agents, clindamycin, tetracycline, and metronidazole; five of seven were sensitive to chloramphenicol; and not one was sensitive to the aminoglycosides, vancomycin, ciprofloxacin, or erythromycin . Seven patients had one or more possible portals of entry for bacteremia, including mucositis (four patients), mucositis plus esophageal lesions (two), and possible mucositis plus diverticulitis (one) . L . buccalis should be considered a potential pathogen in neutropenic patients, especially when breaks in the mucosal breaks in the mucosal barriers are present.

J Invertebr Pathol, 1991 Mar, 57(2), 166 - 71
Rickettsiae in gill epithelial cells of the hard clam, Mercenaria mercenaria; Fries CR et al.; Rickettsiae are found in the gill epithelium of the hard clam, Mercenaria mercenaria . The procaryotes occur free in the cytoplasm of the epithelial cells at the tip of the filament and in the more proximal cells that support the lateral J cilia . The fine structure of the organisms, showing rippled cell walls, is typical of the rickettsiae . The increasing size of the inclusion representing late phase growth often culminates in lysis of the host cell . Masses (Gram-negative, Feulgen-positive) in ova, similar to those observed in the gill epithelium, suggest that transovarian transmission may occur.

Arch Intern Med, 1991 Mar, 151(3), 603 - 4
Flavimonas oryzihabitans (Pseudomonas oryzihabitans; CDC group Ve-2) bacteremia in the immunocompromised host; Decker CF et al.; Flavimonas oryzihabitans, known previously as Pseudomonas oryzihabitans, and a member of the Centers for Disease Control group Ve-2, is a gram-negative organism that has rarely been implicated as a human pathogen . Flavimonas oryzihabitans appears to be a soil and saprophytic organism that survives in moist environments and is indigenous to rice paddles . To our knowledge, only seven cases of human infection caused by this organism have been reported; they involved four patients with bacteremia and three patients with peritonitis who were receiving continuous ambulatory peritoneal dialysis . In this report, we describe three immunocompromised patients with catheter-associated bacteremia: a patient with cancer, a patient with acquired immunodeficiency syndrome, and a patient with sickle cell disease . There is emerging clinical evidence that F oryzihabitans should be recognized as an organism that is capable of causing human disease, particularly in immunocompromised patients and with the increased usage of permanent catheters.

Am J Physiol, 1991 Mar, 260(3 Pt 2), H832 - 41
Coronary vascular smooth muscle function in E . coli endotoxemia in dogs; Parker JL et al.; The purpose of this study was to determine whether intrinsic contraction-relaxation properties of coronary arteries are altered during acute gram-negative endotoxemia . Coronary vascular smooth muscle (VSM) was evaluated in vitro using large and small left circumflex coronary ring preparations isolated from dogs 4 h after administration of either saline (control; C) or 1.5 mg/kg Escherichia coli endotoxin (ET) . ET dogs exhibited marked systemic hypotension and cardiovascular depression throughout the 4-h in vivo phase of the study accompanied by reduction in total left ventricular myocardial blood flow . Isolated coronary vessels were stretched to the apex of the length-contractile tension curve; no differences were observed in length-active or length-passive tension (vessel compliance) relationships between C and ET vessels . Isometric contractions produced by K+ and prostaglandin F2 alpha (PGF2 alpha) were similar in C and ET coronary arteries . VSM relaxant responses to nitroprusside (NP; 10(-10) to 10(-4) M) were also similar in C and ET vessels . In contrast to the apparent lack of effect of ET on directly acting VSM agents, relaxation responses to the endothelial-dependent vasodilator acetylcholine (ACh) were significantly less in ET vessels . Impaired vasodilator response to ACh was not improved by in vivo treatment with the combination antioxidant therapy of allopurinol, superoxide dismutase, and catalase . We conclude that both depolarization (K+) and receptor (PGF2 alpha)-mediated contractile mechanisms, as well as basal cGMP (NP)-mediated vasodilator mechanisms, remained functional in coronary vasculature during acute endotoxemia . Inhibition of ACh-mediated relaxation in ET vessels suggests altered endothelial-dependent vasodilation in coronary arteries during endotoxemia, but this change did not seem to be associated causally with oxygen free radicals.

Infect Immun, 1991 Mar, 59(3), 1131 - 40
Changes in the surface of Leptospira interrogans serovar grippotyphosa during in vitro cultivation; Haake DA et al.; Surface components of virulent and attenuated Leptospira interrogans serovar grippotyphosa were compared by using Triton X-114 solubilization and phase partitioning, immunoprecipitation of intact organisms, and freeze-fracture electron microscopy . Removal of the leptospiral outer membrane by using 0.1% Triton X-114 was demonstrated by whole-mount electron microscopy and by essentially complete solubilization of a lipopolysaccharidelike substance (LLS) from the outer membrane . Triton X-114 (0.1%) did not solubilize subsurface proteins, such as endoflagellar filaments or penicillin-binding proteins, which are markers for the periplasmic space and inner membrane, respectively . Triton X-114 solubilized material from both the virulent and attenuated strains, which partitioned into the hydrophobic, detergent phase, contained LLS and major proteins of 41 and 44 kDa, which were also immunoprecipitable from intact organisms . The virulent strain contained greater amounts of an LLS component with an apparent molecular mass of 30 kDa (R(f) = 0.57), whereas the attenuated strain contained larger amounts of an LLS component with an apparent molecular mass of 20 kDa (R(f) = 0.74) . Differences in protein components between virulent and attenuated organisms were also detected; whereas the 41- and 44-kDa proteins were immunoprecipitated in equal amounts from both the virulent and attenuated strains, a 33-kDa protein was immunoprecipitated in significantly greater amounts from the attenuated strain . Quantitation of outer membrane particle density by freeze-fracture electron microscopy showed that both strains had a low transmembrane outer membrane protein content compared with that of typical gram-negative bacteria . The virulent and attenuated strains had 443 and 990 particles (P less than 0.000001) per micron, respectively, in the concave outer membrane fracture face . These findings suggest that in vitro cultivation of L . interrogans is accompanied by quantitative and qualitative changes in both LLS and outer membrane-associated proteins.

Clin Orthop, 1991 Mar, (264), 178 - 83
Analysis of 61 cases of vertebral osteomyelitis; Patzakis MJ et al.; Sixty-one cases of bacterial vertebral osteomyelitis from July 1969 to July 1979 were analyzed . The ages of the 49 men and 12 women ranged from 21 to 66 years . The portal of entry was hematogenous in 58 cases, gunshot wounds in two cases, and and adjacent retroperitoneal abscess in one case . Biopsy was performed in 60 patients . There were 15 complications related to the disease . Gram-negative rods were the predominant bacteria isolated . Blood culture was positive in 13 of the 26 (50%) patients tested . Eleven of the 13 (85%) organisms isolated from the blood cultures correlated with organisms recovered from biopsy specimens . Eleven of the patients had more than one disk level involved . Of the 61 patients, 29 went on to spontaneous fusion, 17 were lost to follow-up study, 11 failed to fuse, three had surgical fusion, and one patient died . Recommendations for diagnosis included the collection of blood cultures and radionuclide bone scans . Management recommendations included systemic antibiotics for at least three weeks and immobilization with either bed rest or spinal orthoses . Surgery was indicated if an abscess was present, neurologic complications occurred, instability became a factor, or the medical treatment failed.

Jpn J Antibiot, 1991 Mar, 44(3), 337 - 44
{Clinical effect of the combined use of aztreonam, amikacin and clindamycin in infectious disease in obstetrics and gynecology}; Chimura T et al.; Clinical effects of combined use of aztreonam (AZT), amikacin (AMK) and clindamycin (CLDM) in 46 cases with infectious diseases in obstetrics and gynecology were retrospectively studied in 2 groups, and the following results were obtained . 1 . No significant difference in efficacy rates was noted between AZT plus CLDM treated group (n = 25) and AMK plus CLDM treated group (n = 21) (96.0% vs . 95.2%), while rate of excellent efficacy was slightly higher in AZT plus CLDM group than AMK plus CLDM group (24.0% vs . 14.3%) . 2 . No significant difference in bacteriological clinical effects was also noted between the 2 groups, while bacteriological eradication rate was higher in the AZT plus CLDM group than in the other group (76.2% vs . 50.0%), and the difference was particularly clear in the eradication rates of aerobic, Gram-negative bacteria (88.9% vs . 30.0%) . 3 . Subjective and objective side effects, and abnormalities of clinical test results were not found in either group.

J Bacteriol, 1991 Mar, 173(5), 1722 - 8
C-factor has distinct aggregation and sporulation thresholds during Myxococcus development; Kim SK et al.; C-factor, the protein product of the csgA gene, acts as a short-range morphogenetic signal . It is required for fruiting body development of the gram-negative bacterium Myxococcus xanthus . Aggregation, sporulation, and expression of a set of genes that are C-factor dependent, all of which fail in csgA mutant cells, are completely restored by addition of purified C-factor . We report here that, depending on its concentration, C-factor can elicit two distinct morphogenetic and transcriptional responses from csgA cells . Low levels of C-factor bring about aggregation and expression of an early C-dependent gene, whereas higher levels lead to the same effects plus expression of a late C-dependent gene and spore formation . C-factor positively regulates its own transcription . An approximately fourfold net increase in csgA transcription and C-factor levels during development was measured . We propose that autoregulation and the two distinct activity thresholds allow C-factor to act as a timer, first triggering aggregation, then sporulation, thereby producing the appropriate developmental order.

Am J Pathol, 1991 Mar, 138(3), 521 - 4
The intratracheal administration of endotoxin and cytokines . III . The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation; Ulich TR et al.; Endotoxin, a lipopolysaccharide (LPS) component of gram-negative bacteria, induces alveolar macrophages to express interleukin-1 (IL-1) . Lipopolysaccharide and IL-1 both cause severe acute neutrophilic inflammation in the lung after intratracheal injection, suggesting that LPS-induced IL-1 expression contributes to the pathogenesis of LPS-induced acute inflammation . In the present study, the role of IL-1 in LPS-induced acute pneumonia was investigated by quantitating the acute inflammation occurring at 6 hours after the intratracheal injection of LPS as compared to the same timepoint after the intratracheal coinjection of LPS and IL-1 receptor antagonist (IL-1ra) . The IL-1ra was found to inhibit LPS-induced acute inflammation (P greater than 0.0001) as measured by the number of neutrophils recovered in bronchoalveolar lavage . The LPS-induced emigration of neutrophils was inhibited by as much as 45% . Recombinant IL-1 beta-induced neutrophil emigration into the lung was inhibited by 95% when IL-1ra was coinjected intratracheally with IL-1 beta . Coinjection of recombinant IL-1 beta and LPS increased the neutrophilic exodus as compared to the intratracheal injection of either agent alone . Intratracheal injection of LPS induces a progressive increase in IL-1ra mRNA expression in whole-lung RNA preparations, suggesting that endogenous IL-1ra may play an important role as a negative feedback mechanism to downregulate LPS initiated IL-1-mediated acute inflammation . In conclusion IL-1ra inhibits both LPS- and IL-1-induced neutrophilic inflammation and may therefore prove clinically useful as an anti-inflammatory agent for the therapy of either septic or aseptic IL-1-mediated acute inflammation.

Vaccine, 1991 Mar, 9(3), 170 - 6
Secondary in vitro B lymphocyte (antibody) response to microbial antigens: use in appraisal of vaccine immunogenicity and cytokine immunoregulation; Ohmann HB et al.; In order to perform preliminary evaluations of subunit vaccine candidates before extensive trials in large food-producing animals, an in vitro B-lymphocyte response assay, based on the principles of an ELISA, was established . The assay was developed in detail for the porcine system using antigens from the Gram-negative bacterium Actinobacillus pleuropneumoniae, but is shown to be applicable to other species and antigens, including viral components . It is further shown that B-cell activity in the assay is dependent on T-helper cells as well as macrophages and/or their secretory products . Thus, in addition to providing a tool for evaluation of T and B memory cell activity, the system also lends itself to dissection of T-B cell collaboration and the regulatory functions of interleukins in secondary (in vitro) antibody responses.

Jpn J Pharmacol, 1991 Mar, 55(3), 339 - 49
Hydroxyl radical participation in the in vitro effects of gram-negative endotoxin on cardiac sarcolemmal Na,K-ATPase activity; Taga R et al.; The effect of in vitro exposure of sarcolemmal membrane (SL) vesicles to Gram-negative endotoxin lipopolysaccharides (LPS) was studied . LPS decreased the Na,K-ATPase activity of SL vesicles; this effect was inhibited by hydroxyl radical (.OH) scavengers such as dimethylthiourea and dimethyl sulfoxide, but not by superoxide dismutase, a scavenger of superoxide anion radicals or by the hydrogen peroxide scavenger catalase . ESR spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide verified the generation of .OH from LPS itself under the conditions used; .OH generated from LPS was not affected by deferoxamine, a powerful iron chelator . The Na,K-ATPase activity was reduced by an .OH radical generating system consisting of dihydroxyfumarate and Fe3(+)-ADP . Furthermore, exposure of SL vesicles to LPS caused an increase in malondialdehyde formation . It can be concluded that LPS damages cardiac SL by an oxygen free radical mechanism by the generation of .OH, due to inhibition of Na,K-ATPase activity and peroxidation of lipids, and that the effect of LPS is not dependent on the presence of contaminating iron.

N Engl J Med, 1991 Feb 14, 324(7), 429 - 36
Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin . A randomized, double-blind, placebo-controlled trial . The HA-1A Sepsis Study Group; Ziegler EJ et al.; BACKGROUND . HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia . METHODS . To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection . The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin) . Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol . RESULTS . Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture . For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014) . For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017) . Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients . Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038) . No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia . For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24) . All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected . CONCLUSIONS . HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

Proc Natl Acad Sci U S A, 1991 Feb 15, 88(4), 1389 - 93
Iteron inhibition of plasmid RK2 replication in vitro: evidence for intermolecular coupling of replication origins as a mechanism for RK2 replication control; Kittell BL et al.; The broad-host-range plasmid RK2 and its derivatives are maintained in Gram-negative bacteria at a specific copy number that appears to be determined by a series of direct repeats (iterons) located at the RK2 replication origin and by the RK2 replication initiation protein . TrfA . An in vitro replication system was developed from Escherichia coli that is active with either the intact eight-iteron RK2 origin or a minimal five-iteron RK2 origin when purified TrfA protein is provided . Using this in vitro replication system, we have examined the mechanism(s) of copy-number control . It was found that two or more RK2 iterons present on a supercoiled compatible plasmid molecule are capable of specifically inhibiting in vitro the replication of either functional RK2 origin plasmid and that this inhibition is not overcome by adding increasing amounts of TrfA protein . A mutant TrfA protein, TrfA-33(cop254D), that increases the copy number of an RK2 origin in vivo exhibits replication kinetics and activity levels in this in vitro system similar to that of the wild-type protein . However, RK2 in vitro replication initiated by TrfA-33(cop254D) has a much reduced sensitivity to iteron inhibition . These data support a model for RK2 copy-number control that involves intermolecular coupling between TrfA-bound iterons.

Schweiz Med Wochenschr, 1991 Feb 2, 121(5), 145 - 9
{Immunoglobulin deficiency after repeated plasmapheresis}; Stebler C et al.; In 10 patients with Guillain-Barre syndrome the level of globulins and immunoglobulins before and after plasmapheresis was investigated . As a plasma substitute either PPL (in 8 patients) or a plasma substitute solution rich in immunoglobulins (in 2 patients) was used . When plasma was substituted with PPL, the globulins and immunoglobulins dropped to a mean of 40% of the initial value (range 30-60%) after the first plasmapheresis . With daily or alternate day plasmapheresis, the globulins only partially recovered . Before the second plasmapheresis they were still reduced to a mean of 50% (range 20-50%), and dropped further with ongoing exchanges to a mean of 33% (range 20-50%) as measured before the third plasmapheresis . Accordingly, there was a loss of immunoglobulins of similar magnitude . With the use of a plasma substitute solution rich in immunoglobulins (IRP), globulins could be maintained at normal levels . The lowest immunoglobulin values measured after plasmapheresis were 6 g/l (normal range 8-17 g/l) . One patient developed gram-negative septicaemia after plasmapheresis with PPL, possibly due to a low immunoglobulin concentration . We conclude that a plasma substitute solution rich in immunoglobulins should be used for therapeutic plasmapheresis in order to maintain physiological immunoglobulin concentrations.

Circ Shock, 1991 Feb, 33(2), 108 - 20
Comparative and interactive in vivo effects of tumor necrosis factor alpha and endotoxin; Ciancio MJ et al.; A comparative and interactive analysis of the effects of tumor necrosis factor alpha (TNF) and endotoxin (ETX) on selected hemodynamic and glucoregulatory alterations was performed in conscious, unrestrained, adult male Holtzman rats . Rats with indwelling carotid artery and jugular vein cannulae were administered intravenous (i.v.) bolus injections of either (1) ETX at 1.55 or 30 mg/kg; (2) TNF at 0.1, 0.5, or 1.0 mg/kg; or (3) TNF plus ETX as a low dose co-treatment at 0.1 mg/kg plus 1.55 mg/kg, respectively . Control groups received either saline or heat-inactivated TNF . TNF induced a lethal response such that 1.0 mg/kg resulted in five out of six deaths within 6 hr . Elevated pulse rates, early hyperglycemia, late hypoglycemia, hyperlactacidemia, hypoinsulinemia, and elevated catecholamine concentrations were evident after injection of 1.0 mg/kg TNF . The pathophysiological alterations observed after 1.0 mg/kg TNF were comparable to the changes observed after the administration of a highly lethal, 30 mg/kg dose of ETX (six out of six deaths within 24 hr) . Co-treatment with low doses of TNF plus ETX resulted in the rapid demise of the rats, resulting in six out of six deaths within 4 hr . The resultant shocklike state was accompanied by significant hypotension, hyperglycemia and hyperlactacidemia, similar to the changes induced by highly lethal doses of TNF or ETX alone . This study supports the involvement of TNF in the pathogenesis of gram-negative septic shock and documents the hemodynamic and glucoregulatory alterations which accompany the exacerbated shocklike state induced after co-treatment with separately, minimally lethal doses of TNF plus ETX.

Behring Inst Mitt, 1991 Feb, (88), 216 - 21
Anti-lipopolysaccharide antibodies in gram-negative bacteremia; Baumgartner JD; The experimental and clinical studies underlying the concept of cross-protection afforded by core lipopolysaccharides (LPS) antibodies are reviewed . These studies did not allow to clarify the epitope(s) and the effector mechanism(s) involved in the protection . Recently, two antilipid A IgM monoclonal antibodies, called E5 and HA-1A, have been investigated in patients with Gram-negative infections and a clinical picture of septicemia . E5 reduced the mortality of patients, bacteremic or not, but only as long as they were not in shock . A confirmatory study has been initiated . In contrast to E5, HA-1A protected patients in shock, but only when they were bacteremic at randomization . However, experimental studies have yielded contradictory results concerning the protective power of this antibody . Although the clinical studies suggest a beneficial effect of both antibodies in some patients, no definitive conclusions can be drawn until the extensive data will be published, and until further experimental investigations will have clarified the protective power of these antibodies.

Behring Inst Mitt, 1991 Feb, (88), 120 - 4
The beneficial effects of localized tumor necrosis factor production in BCG infection; Kindler V et al.; Inflammatory responses to infectious agents involve different cell populations, including monocytes/macrophages, granulocytes, eosinophils, mastocytes and lymphocytes, which realize a cooperative network aimed at microbial clearance . The recruitment and activation of these inflammatory cells is mediated by a series of cytokines synthesized by distinct elements of the immune system . In particular, the production of tumor necrosis factor (TNF) is known to be induced during the course of various infectious processes . TNF is now recognized to be the major effector of gram-negative endotoxic shock . Experimental and clinical studies have documented the systemic release of TNF during bacterial and parasitic infections, and TNF is considered to account for some of the severe metabolic and tissular damages associated with such disease states . In contrast, we have shown that during BCG infections TNF is produced transiently and focally by granulomas in response to mycobacterial challenge and that it contributes to their containment and elimination . These observations suggest that the localized release of TNF may play a pivotal role in defense mechanisms against microorganisms, while its overproduction, leading to systemic release during severe infections, might be held responsible for a wide range of tissular injuries.

Curr Eye Res, 1991 Feb, 10(2), 121 - 6
Ocular permeability after systemic administration of endotoxin in humans; Herman DC et al.; Acute anterior uveitis in response to the administration of systemic gram-negative endotoxin was studied in humans . The blood-aqueous barrier was evaluated in eight normal human subjects at 8 or 24 hours after systemic administration of purified gram-negative endotoxin . No significant changes in the blood-aqueous barrier were found, as evaluated by permeability to fluorescein, number of aqueous cells, flare, or intraocular pressure, despite profound endotoxin-induced cardiac, pulmonary, and circulatory effects . Gram-negative endotoxin does not appear to affect the human blood-aqueous barrier in doses that can safely be given to humans.

Wei Sheng Wu Xue Bao, 1991 Feb, 31(1), 36 - 40
{Use DNA techniques to detect tetracycline resistance genes in clinical strains}; Zhang Y et al.; Our purpose in the present report was to use DNA techniques to analyse the distribution of Tetracycline resistance determinants among Gram negative bacteria and different location in our country . 306 clinical isolates, 102 out of which were isolated from nosocomial infections in Beijing Union Medical College Hospital from 1981-1986, were identified by fifteen kinds of biochemical reaction . According to sensibility test results, the percentage of resistant to antibiotics was that: Tetracycline 100%, Ampicillin 81.4%, Cefazolin 28.4%, Gentamycin 56.9%, Chloramphenicol 59.8%, TMP-SMZ 57.2%, Erythromycin 91.5% . The result of colony hybridization was that TetB (on R222) occurred at 31.4%, followed by TetD (on RA1) at 25.2%, TetA (on RP1) at 12.4% and TetC (on pSC101) at 10.5%, 36.6% of isolates failed to hybridize to any of the probes, while 51.3% harbored one determinant, 7.5% harbored two, 2.9% three and 1.6% four . Strains from some location contained TetB and TetD were slightly higher than TetC and TetA . At high stringency conditions of hybridization, we were able to show cross reaction of determinant C with TetA DNA, but no reaction with TetB and TetD DNA.

Nihon Kyobu Shikkan Gakkai Zasshi, 1991 Feb, 29(2), 153 - 8
{Sepsis and ARDS}; Kawai S; Basic therapeutic methods based on early diagnosis of septic ARDS were described . Concerning early diagnosis exertional hypoxemia and increased broncho-vascular markings on chest X-ray were observed in the pre-ARDS stage of septic patients . These findings were also observed in the initial stage of endotoxin-induced pulmonary edema in rabbits and the basic mechanisms were thought to be as follows, based or our experimental studies . The former is related on impairment of alveolar diffusion and the latter reflect increased peri-vascular cuffing due to increase in pulmonary edema . The diffuse infiltrative shadows on the both back area in CT scanning was also a helpful sign indicating the early stage of pulmonary edema . This finding was seen at the stage at which the edematous shadow had not yet appeared on conventional chest X-ray . Increase in serum laminin and decrease in plasma fibronectin were also important biochemical findings predicting ARDS in gram negative sepsis . Using these findings, it is considered that early prediction of septic ARDS is possible . Concerning therapeutic methods based on early prediction, the usefulness of cortico-steroids and the protease inhibitor "Urinastatin" were observed in experimental in vitro and in vivo studies . Some findings induced by endotoxin administration in rats or rabbits, such as the increase in endotoxin in peripheral blood, the distraction of PMN-elastase, the increase in pulmonary lymph flow and mortality within 48 hours were significantly suppressed by simultaneous treatment by corticosteroid . In an in vitro study, PMN superoxide production and elastase release following incubation of endotoxin and PMNs were significantly inhibited by adding a concomitant level of corticosteroid and/or urinastatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrob Agents Chemother, 1991 Feb, 35(2), 256 - 8
Association with prior fluoroquinolone therapy of widespread ciprofloxacin resistance among gram-negative isolates in a Veterans Affairs medical center; Muder RR et al.; We performed a case-control study of risk factors for the acquisition of ciprofloxacin-resistant gram-negative isolates in a Veterans Affairs medical center . Sixty-five patients with resistant isolates and 50 control patients were identified . Prior fluoroquinolone use was significantly more frequent among patients with resistant isolates than it was among controls (58 versus 20%; P = 0.0001) . The association with prior quinolone use was stronger in the long-term-care division (81 versus 32%; P = 0.0005) than it was in the acute-care division (29 versus 0%; P = 0.015) . On multivariate analysis, prior receipt of a fluoroquinolone was the single most significant risk factor for isolation of a ciprofloxacin-resistant gram-negative organism (P = 0.0001).

J Clin Pharmacol, 1991 Feb, 31(2), 158 - 63
Amikacin pharmacokinetics: wide interpatient variation in 98 patients; Zaske DE et al.; The disposition of amikacin was studied in 98 patients receiving treatment for severe gram-negative sepsis . Several factors were identified which were significantly related to the drug's elimination rate . These included renal function (r = .67), age (r = -.55), distribution volume (r = .34), and weight (r = -.31) . These variables explain 62% of the variance (R2) in elimination rate constant when combined in a multiple regression model . The drug's half-life demonstrated considerable interpatient variation in patients with a normal serum creatinine (.68-14.4 hrs) or with a normal creatinine clearance (.68-7.2 hrs) . The drug's distribution volume ranged from .08 to .48 L/Kg . The drug's clearance varied from 6.5 to 200 mL/hr/kg for patients with a normal serum creatinine and 17.8 to 200 mL/hr/kg for patients with a normal creatinine clearance . The interpatient variation in the drug's kinetic parameters is a concerning clinical problem . Measuring serum amikacin concentrations and adjusting dosage regimens are necessary to achieve desired peak and trough serum concentrations.

Neurosurgery, 1991 Feb, 28(2), 242 - 50
Cerebrospinal fluid flow dynamics in children with external ventricular drains; Drake JM et al.; Fifty-five children had 64 external ventricular drains (EVDs) placed predominantly (95%) for cerebrospinal fluid (CSF) shunt infections . In 9 children, a computer monitoring system measured the CSF output each second continuously for up to 24 hours . The monitoring was repeated daily for up to 9 days . The state of arousal of the patients was recorded simultaneously . In all children, daily EVD outputs were related to age, sex, weight, method of establishing the EVD, height of the drip chamber, time since insertion, and type of infecting organism . Computer monitoring revealed wide fluctuations in flow rate, with peak rates frequently greater than 20 ml/h and periods of flow arrest . These changes were usually associated with increased arousal, but also occurred with sleep . The mean EVD flow rate for all children was 6.3 ml/h . EVD output increased with age and weight . EVD output decreased with Gram-negative or multiple-organism infections and with elevation of the drip chamber . Resolution of the infection, sex of the patient, and method of establishing the EVD had no effect on output . These results predict that CSF production increases with brain growth in humans: that CSF production is depressed by Gram-negative and multiple-organism infections: that implanted CSF shunts with standard valves flow at equivalent rates to an EVD in the supine position; and that the CSF drainage requirements in this group are approximately equal to their EVD outputs.

Am J Physiol, 1991 Feb, 260(2 Pt 1), G213 - 9
Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation; DeLa Cadena RA et al.; The plasma kallikrein-kinin system is activated in Gram-negative sepsis and typhoid fever, two diseases in which bacterial products have been shown to initiate inflammation . Because a single intraperitoneal injection of bacterial cell wall peptidoglycan-polysaccharide polymers from group A steptococci (PG-APS) into a Lewis rat produces a syndrome of relapsing polyarthritis and anemia, we investigated changes in the role of the kallikrein-kinin system in this model of inflammation . Coagulation studies after injection of PG-APS revealed an immediate and persistent decrease in prekallikrein levels . High-molecular-weight kininogen levels decreased significantly during the acute phase and correlated with the severity of arthritis . Factor XI levels were decreased only during the acute phase . Antithrombin III levels remained unchanged, indicating that neither decreased hepatic synthesis nor disseminated intravascular coagulation caused the decreased plasma contact factors . Plasma T-kininogen (an acute phase protein) was significantly elevated during the chronic phase . PG-APS failed to activate the contact system in vitro . Thus the kallikrein-kinin system plays an important role in this experimental model of inflammation, suggesting that activation of this system may play a role in the pathogenesis of inflammatory bowel disease and rheumatoid arthritis in which bacterial products might be etiologically important.

Clin Exp Immunol, 1991 Feb, 83(2), 267 - 73
Detection of human and murine common idiotypes of DNA antibodies in tissues and sera of patients with autoimmune diseases; Watts RA et al.; The expression in tissue and serum of a panel of murine and human common DNA antibody idiotypes (Ids) (BEG 2, PR 4, F-423, I-402, II-28, IV-228, V-88) has been investigated . The murine V-88 Id was detected in eight out of 10 and the human BEG 2 Id in five out of 10 labial biopsies from patients with Sjogren's syndrome . The murine F-423, I-402 and IV-228 Ids were identified in one out of 10 biopsies . In each case the pattern of staining was similar with staining of the acinar basement membrane and a cell population . Using double-labelling immunohistochemistry this cell population were identified as plasma cells . No staining was seen in four normal labial biopsies . The V-88 Id was detected on the epithelial aspect of the thickened basement membrane in three out of nine renal biopsies from patients with systemic lupus erythematosus (SLE) . None of the other Ids (BEG 2, PR4, IV-228, F-423 or I-402) could be detected in renal tissue . None of the Ids were found in skin biopsies from SLE patients . Id V-88 may, like the 16/6 Id to which it is phenotypically related, play a role in the pathogenesis of renal lesions in SLE . The BEG 2 Id could be detected in the serum of patients with rheumatoid arthritis (RA) and active untreated tuberculosis . Ids II-28, V-88 and I-402 were elevated in serum from patients with Sjogren's syndrome and II-28 Id in serum from patients with myositis and RA . None of the Ids were elevated in serum from patients with SLE . Apart from the BEG 2 Id, none of the Ids were elevated in serum from patients with tuberculosis or Gram-negative infections . The presence of murine Ids in human tissue and serum suggests that they are cross-species idiotypes and have been conserved through evolution.

Am J Surg, 1991 Feb, 161(2), 300 - 4
Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat; Barber AE et al.; Bacterial translocation occurs in animal models of shock, trauma, sepsis, and parenteral or elemental enteral alimentation . Bowel atrophy and cecal bacterial overgrowth have both been implicated in the pathophysiology of bacterial translocation in many of these models . To further define the etiology of bacterial translocation resulting from dietary manipulations, rats were fed a elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized to either intestinal decontamination with a nonabsorbable antibiotic (neomycin) or no antibiotic treatment . Neomycin treatment significantly (p less than 0.01) reduced the incidence of bacterial translocation after DFD, in association with a significant reduction in the number of cecal gram-negative bacteria . Neither loss of bowel mass after DFD nor bowel composition was affected by oral neomycin . Bacterial translocation after DFD would thus appear to be the result of cecal bacterial overgrowth rather than a loss of a physical intestinal barrier due to atrophy.

Endocrinology, 1991 Feb, 128(2), 645 - 53
Gram-negative infection increases noninsulin-mediated glucose disposal; Lang CH et al.; Peripheral glucose uptake can occur by either insulin- or noninsulin-mediated mechanisms, and the two pathways appear to be regulated independently . Using the euglycemic hyperinsulinemic clamp technique, we have previously demonstrated that sepsis induces whole body insulin resistance . The purpose of the present study was to determine whether infection also alters noninsulin-mediated glucose uptake (NIMGU) and, if so, which tissues are affected . Studies were performed in chronically catheterized conscious rats under either basal (6 mM glucose, 30 microU/ml insulin) or insulinopenic conditions to determine NIMGU . Hypermetabolic sepsis was induced by sc injections of live Escherichia coli, and 24 h later a tracer amount of {U-14C}deoxy-2-glucose was injected for the determination of the in vivo glucose metabolic rate (Rg) in selected tissues . Our results indicate that NIMGU is the predominant route of glucose disposal in both septic and nonseptic rats, accounting for 79-83% of the total rate of glucose disposal . Because the rate of whole body glucose disposal was increased by sepsis, the absolute rate of NIMGU was 46% higher in septic rats than in nonseptic animals . This increase was the result of the elevated Rg in liver, spleen, ileum, and lung . Sepsis also increased whole body insulin-mediated glucose uptake by 88% under basal conditions, and this was due to an enhanced glucose uptake by muscle and skin . In insulinopenic animals in which the plasma glucose concentration was elevated to 17 mM, whole body glucose disposal increased by 107% in nonseptic animals, but by only 32% in septic rats . The hyperglycemic-induced increment in organ Rg was smaller in all tissues examined from septic animals . However, the absolute rate of whole body and tissue glucose utilization was not different between the two groups . These results indicate that gram-negative infection increases whole body NIMGU, which results from an enhanced rate of glucose utilization by tissues rich in mononuclear phagocytes, including the liver, spleen, ileum, and lung, but not by muscle.

Infect Immun, 1991 Feb, 59(2), 478 - 85
Intracellular and extracellular enzymatic deacylation of bacterial endotoxin during localized inflammation induced by Escherichia coli; McDermott CM et al.; Acyloxyacyl hydrolase (AOAH), an enzyme that removes the secondary acyl chains of gram-negative bacterial lipid A (endotoxin), has been identified previously in human neutrophils and mouse macrophages . We report here that bovine leukocytes also contain AOAH activity . Although bovine AOAH deacylates bacterial lipopolysaccharide in a manner similar to human AOAH, it is active in vitro over a broader pH range, from 4.0 to 7.0 . By using Escherichia coli infection of the bovine mammary gland as a model of localized gram-negative bacterial disease and associated tissue inflammation, AOAH activity per leukocyte increased . In addition, AOAH activity increased in the cell-free portion of infected mammary secretions . These data indicate that AOAH activity increases in leukocytes associated with inflammation induced by gram-negative bacteria and provide additional evidence of its potential involvement in the defense against the effects of bacterial endotoxin.

Proc Natl Acad Sci U S A, 1991 Jan 15, 88(2), 345 - 9
Pertactin, an Arg-Gly-Asp-containing Bordetella pertussis surface protein that promotes adherence of mammalian cells; Leininger E et al.; A 69-kDa protein has been identified on the surface of the Gram-negative pathogen Bordetella pertussis that can elicit a protective immune response in animal models . This protein is associated with virulent strains of B . pertussis but its function has remained unclear . In this report we demonstrate that purified preparations of the 69-kDa outer membrane protein can promote the attachment of Chinese hamster ovary (CHO) cells . The interaction between the mammalian cells and this protein can be specifically inhibited by an Arg-Gly-Asp (RGD)-containing synthetic peptide that is homologous with a region found in the 69-kDa protein sequence . These studies indicate that a specific cell binding site containing an Arg-Gly-Asp sequence may be involved in the interaction of this bacterial protein with mammalian cell surfaces . To further investigate the role of this protein as a bacterial adhesin, a mutant of B . pertussis W28 that does not express the 69-kDa protein was constructed using the plasmid vector pRTP1 . This mutant was 30-40% less efficient at adhering to CHO cells and to human HeLa cells than was the parent strain . These data support a role for this 69-kDa outer membrane protein in the attachment of B . pertussis to mammalian cells . We propose the name "pertactin" for this protein.

Perit Dial Int, 1991, 11(1), 69 - 71
Recovery of S . epidermidis and E . coli from effluent peritoneal dialysate; Bailie GR et al.; The effect of incubation temperature and duration was studied on the growth of organisms in peritoneal dialysate effluent . Penicillin-sensitive, and gentamicin-sensitive clinical isolates of S . epidermidis (SE) and E . Coli (EC), respectively, were inoculated into freshly drained dialysate of 19 CAPD patients who did not have peritonitis . Each dialysate was 1.5% dextrose in strength and had a minimum dwell of 6 hours . Control and test aliquots were incubated at 4 degrees C, 20 degrees C and 37 degrees C for periods of up to 12 hours, and samples collected and plated to determine colony counts . Initial counts at time zero were 9.4 x 10(4) (SE) and 6.6 x 10(3) (EC) CFU/ml . SE showed no change in count at 4 or 20 degrees C up to 12 hours . There was a significant increase (p less than 0.005) at 37 degrees C, at 12 hours to 1.72 x 10(6) CFU/ml . EC showed no change at 4 or 20 degrees C . There was a significant decrease in count for EC at 37 degrees C, 6 hours (5.5 x 10(2) CFU/ml, p less than 0.01) and 37 degrees, 12 hours (2.9 x 10(2) CFU/ml, p less than 0.0001) . It is recommended that infected dialysate should be stored in cool conditions until it can be transported for culture to ensure adequate recovery of gram negative organisms.

Z Gesamte Hyg, 1991 Jan, 37(1), 36 - 9
{Determining the pattern of outer membrane proteins of gram-negative bacteria as a contribution to complex typing}; Seltmann G et al.; The aim of these investigations was to study relations between the serotype of E . coli strains and the pattern of their outer membrane proteins ("OMP") in sodium dodecylsulfate polyacrylamide gel electrophoresis . Three groups of strains being well characterized at least serologically (01, 02, 018ac containing different K, H, and in part F antigens) were submitted to this analysis . In all cases a nearly complete paralellity between OMP pattern and O:K:H(F:) type was observed, provided that the strains were epidemiologically related . The possibility is discussed that the OMP type could be used as a guide marker for the complex typing of E . coli strains.

Surg Gynecol Obstet, 1991, 172 Suppl, 30 - 5
A randomized trial of ticarcillin and clavulanate versus gentamicin and clindamycin in patients with complicated appendicitis; Sirinek KR et al.; Secondary bacterial peritonitis is usually a polymicrobial infection of facultative gram-negative aerobic and anaerobic organisms . Treatment consists of operation and broad-spectrum antibiotic administration . The antibiotic treatment of choice in these infections has been the combination of gentamicin and clindamycin . However, this combination can have toxic side effects and necessitates frequent monitoring of serum levels . Beta-lactam antibiotics provide broad-spectrum coverage and low toxicity, but can be inactivated by species of bacteria producing beta-lactamase enzymes . Clavulanic acid is a potent inhibitor of beta-lactamases and has been shown to extend the efficacy of ticarcillin to bacteria producing these enzymes . This combination was compared with gentamicin and clindamycin in 99 consecutive patients with complicated appendicitis . Eradication of identified pathogens was greater in the ticarcillin and clavulanate group (98 per cent) than in the gentamicin and clindamycin group (92 per cent), even for the subgroup of organisms producing beta-lactamases (97 versus 90 per cent eradication) . Complications and clinical response were not significantly different between the two treatment groups . Ticarcillin and clavulanic acid is a safe and effective alternative to gentamicin and clindamycin in the treatment of secondary bacterial peritonitis and offers advantages in dosing simplicity and freedom from ototoxic and nephrotoxic effects.

J Comp Pathol, 1991 Jan, 104(1), 57 - 64
A comparison of central nervous lesions directly induced by Escherichia coli lipopolysaccharide in piglets, calves, rabbits and mice; Nakajima Y et al.; To evaluate the role of endotoxin during Gram-negative bacterial meningitis, the nervous lesions of piglets, calves, rabbits and mice were compared by direct inoculation of Escherichia coli lipopolysaccharide into the central nervous system . Suppurative leptomeningitis was induced in piglets by small doses of lipopolysaccharide . Mice also had a mild suppurative inflammation in the leptomeninges . In contrast, calves showed suppurative pachymeningitis, but no lesions in the leptomeninges . Leptomeningeal inflammation was not induced in rabbits . Induction of the leptomeningitis by endotoxin was compared with sensitivity to intravenous or intraperitoneal endotoxin in these species.

Prostaglandins Leukot Essent Fatty Acids, 1991 Jan, 42(1), 61 - 5
Free radical generation, lipid peroxidation and essential fatty acids in patients with septicemia; Prabha PS et al.; Infections due to gram-negative bacteria and other organisms can lead to septicemia and shock in some patients . Endotoxins, which cause these pathophysiological events, stimulate macrophages to elaborate tumor necrosis factor and other lymphokines . These lymphokines can augment free radical generation by polymorphonuclear leukocytes, macrophages and other cells, which may ultimately produce respiratory distress syndrome, multiorgan failure and irreversible shock seen in septicemia . This is supported by our results presented here that there is indeed an increase in free radical generation and lipid peroxidation in patients with septicemia . In addition, analysis of plasma lipid profile in these patients showed that gamma-linolenic, dihomogamma-linolenic and arachidonic acids of n-6 series and alpha-linolenic and eicosapentaenoic acids of the n-3 series are decreased in their plasma phospholipid fraction . These results suggest that free radicals, lipid peroxides, and alteration in essential fatty acid metabolism may have a role in the pathogenesis of septicemia.

FEMS Microbiol Lett, 1991 Jan 1, 61(1), 39 - 43
Location and identification of substituents with free amino group in lipopolysaccharides of gram-negative bacteria with the use of chromophore labelling; Dmitriev BA et al.; Interaction of ten different lipopolysaccharides (LPS) with 2,4-dinitrofluorobenzene yielded quantitatively yellow dinitrophenyl derivatives (DNP-LPS) to show the presence of substituents with free amino group . The DNP-LPS samples were degraded with 1% acetic acid, and after removal of lipid A precipitates the supernatants were separated on a Sephadex G-25 column to give coloured polysaccharide, oligosaccharide and monomeric fractions monitored at lambda DNP = 365 nm . The coloured materials, including DNP-derivative of lipid A, were dephosphorylated with hydrofluoric acid followed by identification of the released DNP-amines by thin layer chromatography (TLC) on silica gel . Subsequently, the dephosphorylated materials were hydrolysed with hydrochloric acid followed by TLC analysis . The approach allowed to detect, locate and identify the substituents with free amino group within the LPS molecules . Moreover, two types of core structures within LPS preparation from one strain were discovered for five microorganisms.

J Bacteriol, 1991 Jan, 173(1), 404 - 6
Chromogenic method for rapid isolation of recA-like mutants of gram-negative bacteria; Barbe J et al.; We have devised a rapid and widely applicable color test for detecting recA-like mutants of gram-negative bacteria . The technique depends on decreased expression of an Escherichia coli recA-lacZ fusion in recA mutants and uses a broad-host-range plasmid to transfer the fusion gene into new species . We describe the isolation of a recA-like mutant of Pseudomonas syringae by this technique.

Infect Immun, 1991 Jan, 59(1), 441 - 4
Diphosphoryl lipid A obtained from the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice; Qureshi N et al.; Diphosphoryl lipid A (DPLA) obtained from the nontoxic lipopolysaccharide (LPS) of Rhodopseudomonas sphaeroides ATCC 17023 did not induce interleukin-1 release by murine peritoneal macrophages . However, it blocked this induction by toxic deep-rough chemotype LPS (ReLPS) from Escherichia coli D31m4 . Previously, we obtained similar results on the induction of tumor necrosis factor (TNF) by macrophages . These results showed that DPLA is able to block in vitro the induction of two important mediators of gram-negative bacterial sepsis . We then wanted to determine whether DPLA could also block the induction of TNF by LPS in animals . Mice were treated with 100 micrograms of R . sphaeroides DPLA and challenged 60 min later with 1.0 micrograms of ReLPS from E . coli . The serum TNF level was measured after 60 min . Treatment of mice with this DPLA blocked the rapid and transient rise of TNF caused by ReLPS . This result suggested that R . sphaeroides DPLA might be able to protect animals against endotoxin shock caused by gram-negative bacterial infection.

Infect Immun, 1991 Jan, 59(1), 240 - 6
Legionella pneumophila inhibits protein synthesis in Chinese hamster ovary cells; McCusker KT et al.; Legionella pneumophila is a gram-negative facultative intracellular parasite that causes Legionnaires disease . To explore the interactions between L . pneumophila and host cells, we have developed a continuous cell line model of infection . We show that about 80% of Chinese hamster ovary (CHO) cells were associated with L . pneumophila after incubation for 3 h at a multiplicity of infection of 20 bacteria per cell . Within 3 to 4 h of incubation with L . pneumophila, protein synthesis of CHO cells was markedly inhibited, as shown by the reduction of incorporation of radiolabeled amino acids into proteins . L . pneumophila did not inhibit transport of amino acids or cause degradation of newly synthesized proteins in CHO cells . Cytochalasin D blocked internalization of L . pneumophila by CHO cells, yet CHO cell protein synthesis was inhibited . These results indicated that L . pneumophila could inhibit host protein synthesis from the cell exterior . L . pneumophila that had been killed with antibiotics prior to incubation with CHO cells still inhibited protein synthesis, indicating that the inhibition of CHO cell protein synthesis occurred in the absence of de novo protein synthesis by L . pneumophila.

Chest, 1991 Jan, 99(1), 169 - 75
Endotoxemia in human septic shock; Danner RL et al.; To evaluate the incidence, pattern and clinical importance of endotoxemia in septic shock, frequent, serial endotoxin determinations were made prospectively in patients with shock . Detectable endotoxin occurred in 43 of 100 patients with septic shock, but in only one of ten patients with shock due to nonseptic causes . During septic shock, endotoxemia frequently occurred in the absence of Gram-negative bacteremia . Using a logistic regression model, multiple organ failure occurred 10.3 times more frequently and depression of left ventricular ejection fraction (less than or equal to 45 percent) 4.8 times more frequently in endotoxemic patients . In patients with positive blood cultures, endotoxemia was associated with a high mortality . We conclude that endotoxemia occurs frequently in septic shock and is associated with severe manifestations of this syndrome, including cardiac depression and multiple organ failure . This study suggests that endotoxin is an important mediator of septic shock and supports efforts to develop anti-endotoxin therapies for treating patients with this disease.

J Infect Dis, 1991 Jan, 163(1), 193 - 6
Predictive index for optimizing empiric treatment of gram-negative bacteremia; Leibovici L et al.; In a survey of 296 episodes of gram-negative bacteremia in 286 patients (aged 13-99 years), four clinical variables were found to predict both significantly and independently the subsequent isolation of a multiresistant strain; hospital acquisition of the infection, antibiotic treatment before the bacteremic episode, endotracheal intubation, and thermal trauma as the cause of hospitalization . These variables were combined in an index that served to classify the patients into four groups with an increasing prevalence of multiresistant strains, Pseudomonas isolates, and isolates resistant to each of the antibiotic drugs in common use . For example, the percentage of isolates susceptible to cefuroxime in the four groups were 79%, 56%, 34% and 25%, and to gentamicin, 89%, 79%, 46%, and 33% (P less than .001 for both comparisons) . The performance of the index was validated in a second group of 144 episodes of gram-negative bacteremia . The index kept its discriminative power . Compared with the prescriptions of the attending physicians, the index could probably have improved empiric antibiotic treatment in 24% of patients.

Comp Immunol Microbiol Infect Dis, 1991, 14(3), 223 - 8
The current status of cat-scratch disease: an update; Arlet G et al.; Cat-scratch disease (CSD) is a benign inoculative lymphoreticulosis, first described in independent reports by Pierre Mollaret {1} and Robert Debre in 1950 {2} . The disease usually self-limited, with spontaneous resolution occurring after several weeks, appears to be related to the presence of an identified gram-negative bacteria.

Arkh Patol, 1991, 53(6), 3 - 6
{The role of microbial toxic substances in the pathogenesis of acute intestinal infections}; Shalygina NB; The authors suggest a syndromal approach to the acute intestinal infection pathogenesis provoked by gram-negative bacteria . A brief review of the achievements in the field of pathogenicity of infectious agents is given on the basis of which a conclusion is drawn about the main role of toxins in the clinical manifestation determining the principal syndromes in acute intestinal infections, i . e . diarrhea and inflammation . A pathogenetic syndromal classification of acute intestinal infections is forwarded which allows a practitioner to choose a pathogenetic therapy . The classification is useful for the pharmacologists as well searching for the methods of detoxification.

Proteins, 1991, 11(2), 95 - 110
Expert system for predicting protein localization sites in gram-negative bacteria; Nakai K et al.; We have developed an expert system that makes use of various kinds of knowledge organized as "if-then" rules for predicting protein localization sites in Gram-negative bacteria, given the amino acid sequence information alone . We considered four localization sites: the cytoplasm, the inner (cytoplasmic) membrane, the periplasm, and the outer membrane . Most rules were derived from experimental observations . For example, the rule to recognize an inner membrane protein is the presence of either a hydrophobic stretch in the predicted mature protein or an uncleavable N-terminal signal sequence . Lipoproteins are first recognized by a consensus pattern and then assumed present at either the inner or outer membrane . These two possibilities are further discriminated by examining an acidic residue in the mature N-terminal portion . Furthermore, we found an empirical rule that periplasmic and outer membrane proteins were successfully discriminated by their different amino acid composition . Overall, our system could predict 83% of the localization sites of proteins in our database.

Prog Clin Biol Res, 1991, 367, 9 - 24
The role of cachectin/TNF and other cytokines in sepsis; Zentella A et al.; A traditional view has been that bacterial products, such as endotoxins from gram negative bacteria, have a direct deleterious effect on the host, resulting in fever, hypermetabolism, anorexia, and tissue damage . In recent years, however, it has been shown that endogenous products of the host, secreted by macrophages and other cellular elements of the immune system, act as mediators in activating the metabolic and other physiological changes characteristic of the sepsis syndrome . We will review in depth various aspects of the major, central mediator, i.e., tissue necrosis factor (TNF)/cachectin, and also briefly discuss the interleukins IL-6 and IL-1.

Prog Clin Biol Res, 1991, 367, 179 - 86
Randomized, double-blind phase II study of anti-endotoxin antibody (E5) as adjuvant therapy in humans with serious gram-negative infections; Greenberg RN et al.; Xomen-E5 (E5) is a murine monoclonal IgM antibody (MAb) that binds to the lipid A epitope of endotoxin . The MAb was developed by immunization against the J5 mutant of Escherichia coli . Prior studies in humans have shown safety and T1/2 of 18.4 hours . In this double blind study patients suspected to have life threatening gram-negative infections were randomized to receive 2 doses, 24 hours apart, of placebo (P), 2.5 mg/kg E5, or 7.5 mg/kg E5 . Overall 23 patients had a documented serious gram-negative infection and received at least one dose of study drug . Mortality 3 days after last infusion was 2 of 9 for P, 0 of 9 for 2.5 mg/kg, and 0 of 5 for 7.5 mg/kg . By 21 days after therapy one E5 treated patient had died . Wheezes occurred in one E5 treated patient . Eight of 15 E5 patients treated had IgG anti-murine antibodies by 3 weeks after therapy . These data suggest the need to pursue studies designed to verify that E5 reduced mortality and morbidity in seriously ill patients with gram-negative infections.

Prog Clin Biol Res, 1991, 367, 141 - 59
Anti-lipopolysaccharide and anti-tumor necrosis factor/cachectin antibodies for the treatment of gram-negative bacteremia and septic shock; Calandra T et al.; Endotoxin is composed of lipid A, the toxic moiety, of the core region, a conserved structure among Gram-negative bacteria, and of the O-side chains, a highly variable part responsible for the antigenic specificity . The concept of cross-protection afforded by antiserum raised against the core region of endotoxin is supported by the following data: experimentally antiserum protected against infections caused by a wide range of Gram-negative bacteria or endotoxins; in patients with Gram-negative bacteremia, survival was associated with high levels of anti-core antibodies, and mortality was reduced by the prophylactic or therapeutic use of immune serum or plasma . However, the proof that protection is afforded by cross-protective anti-core antibodies is still lacking . Furthermore, many experimental studies and clinical studies trials have shown controversial results . Ongoing experimental studies and recently completed clinical trials, using either polyclonal or monoclonal anti-core antibodies should help clarify the issues both of the clinical efficacy and of the mechanism of protection . Tumor necrosis factor/cachectin has been unequivocally shown, both in experimental animal models and in humans to be a pivotal mediator of the clinical and humoral manifestations of shock induced by endotoxin or by whole Gram-negative bacteria . In humans, TNF was been transiently detected in the blood of volunteers challenged with endotoxin, in a small proportion of patients with Gram-negative sepsis, but in the vast majority of patients with established septic shock . However, in patients the magnitude and the evolution of the blood concentration of TNF differed from that observed in animal models or in human volunteers after an acute challenge with either Gram-negative bacteria or endotoxin, probably reflecting differences in infectious stimuli . In children with meningococemia and in adults with Gram-negative septic shock, TNF was associated with the patient's outcome . Anti-TNF monoclonal antibodies are presently undergoing clinical investigation in patients with septic shock . However, one should keep in mind that TNF serves both beneficial and detrimental functions depending upon its concentration in body fluids.

Pharmacotherapy, 1991, 11(4), 351 - 2
Neurotoxicity associated with ceftazidime therapy in geriatric patients with renal dysfunction; Slaker RA et al.; Ceftazidime, a beta-lactamase-stable, third-generation cephalosporin, is widely used for the treatment of serious gram-negative infections . Neurotoxicity has rarely been associated with the drug; however, two of our patients developed ceftazidime-induced neurotoxicity that produced confusion, disorientation, agitation, generalized weakness, and myoclonus . In both patients these symptoms cleared with either discontinuation or reduction of the dosage of ceftazidime . This emphasizes the importance of adjusting the dosage of ceftazidime in patients with renal insufficiency.

Neurol Croat, 1991, 40(2), 111 - 6
Entry of ciprofloxacin into cerebrospinal fluid during bacterial, viral and tuberculous meningitis; Barsic B et al.; We studied the entry of ciprofloxacin into the cerebrospinal fluid (CSF) in 37 patients with various types of meningitis (bacterial meningitis 10 patients, viral 12 patients, tuberculous 7 patients) . Eight patients were in the control group with normal CSF finding . Mean ciprofloxacin concentrations in the CSF 50-60 minutes after 200 mg of ciprofloxacin was given in infusion were 0.20 +/- 0.12 mg/L in patients with bacterial meningitis, which was significantly higher than in other tested groups (p = 0.0325) . Ciprofloxacin achieved concentrations in the CSF 6.5-39% of serum (mean value 15% +/- 9%) in the bacterial meningitis group, while in the groups with viral and tuberculous meningitis the levels were significantly lower (approximately 9% of serum) but still higher than in the control group (approximately 5% of serum) . Our data suggest that ciprofloxacin should be very cautiously used in selected patients with bacterial meningitis caused by multiple resistant strains of gram negative bacteria.

Pathobiology, 1991, 59(3), 185 - 8
Regulatory mechanisms of host responsiveness to endotoxin (lipopolysaccharide); Mathison J et al.; During Gram-negative endotoxemia, precise regulation of monocyte/macrophage (M phi) responsiveness to lipopolysaccharide (LPS) is critical to preserve host defense while avoiding complications such as organ failure and death . We will discuss regulation of LPS-M phi interactions by LPS-binding plasma proteins and by LPS-induced changes in M phi responsiveness . Upon exposure to plasma, LPS binds to either lipoproteins or LPS-binding protein (LBP; a 60-kilodalton glycoprotein with a high-affinity binding site for the lipid A moiety of rough and smooth LPS) . The LPS-LBP complex stimulates the M phi by binding to its cellular receptor, CD14 (a monocyte/M phi-specific, phosphatidylinositol-anchored surface glycoprotein) . Pretreatment of whole blood with anti-CD 14 monoclonal antibody reduces the responsiveness of monocytes to LPS {determined by tumor necrosis factor-alpha (TNF-alpha) release}at least 10-fold . Similarly, cellular responsiveness to LPS is diminished at least 100-fold by depletion of plasma LBP with anti-LBP antibody . Compared to LPS-LBP induction of TNF-alpha, LPS-lipoprotein complexes are as much as 10,000-fold less active . Thus, partitioning of LPS between LBP and lipoproteins markedly influences M phi responsiveness to LPS . LPS also directly induces M phi hyporesponsiveness to itself by a process known as adaptation; exposure of M phi to less than or equal to LPS/ml (subthreshold for TNF induction) for 6-9 reduces the sensitivity of the M phi to subsequent challenge up to 1,000-fold, so that 1 microgram/ml rather than 1 ng/ml of LPS is required for maximal induction of TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Med Microbiol Immunol (Berl), 1991, 180(2), 67 - 72
Periodontal regeneration procedures may induce colonization by glycocalyx-producing bacteria; Passariello C et al.; Sixteen patients that underwent periodontal regeneration procedures by implantation of Goretex membranes were studied to evaluate the microbiota that colonized membranes . The microbiological follow-up showed that colonization was principally due to opportunist gram-negative glycocalyx-producing bacteria . The comparison of the microbial flora of treated and untreated sites showed the influence of surface characteristics on the quality of the resident microbiota . These findings suggest the necessity for developing efficient prohylactic protocols for these cases.

Cancer Immunol Immunother, 1991, 33(6), 375 - 81
In situ activation of mouse macrophages and therapy of spontaneous renal cell cancer metastasis by liposomes containing the lipopeptide CGP 31362; Utsugi T et al.; We determined whether the intravenous administration of multilamellar vesicle liposomes (MLV) containing a lipopeptide analogue of a fragment from the cell wall of gram-negative bacteria (CGP 31362) can render BALB/c mouse alveolar macrophages tumoricidal in situ and reduce the incidence of spontaneous lung metastasis of syngeneic renal carcinoma (RENCA) cells . Alveolar macrophages (a) incubated in vitro with MLV containing CGP 31362 (MLV-31362) and (b) harvested from mice injected i.v . with MLV-31362 were rendered cytotoxic against the RENCA cells . Maximum cytotoxic activity of the macrophages was induced by injecting 5 mumol MLV consisting of 250 mg phospholipids and 0.5 mg CGP 31362 . The single i.v . injection of 5 mumol MLV-31362 produced activation of macrophages that lasted for up to 4 days . Repeated i.v . injections of MLV-31362 produced a continuous antitumor activity in alveolar macrophages . To study the lipopeptide's effects on metastasis, we injected the left kidneys of BALB/c mice with RENCA cells . The kidney with growing tumor was resected 10 days later and, after a further 2 days, groups of mice were injected i.v . with MLV-31362 or with MLV-HBSS (twice weekly for 3 weeks) . Treatment with MLV-31362 significantly decreased the median number of spontaneous lung metastases . These data demonstrate that the systemic administration of MLV-31362 can activate murine lung macrophages in situ and reduce the incidence of spontaneous RENCA lung metastases.

Hum Antibodies Hybridomas, 1991 Jan, 2(1), 33 - 8
Effect of production method on the systemic clearance rate of a human monoclonal antibody in the rat; Gauny SS et al.; Pharmacologic studies of human immunoglobulins (IgM) in non-primate animal models, whether directed toward efficacy or toxicity, rely on pharmacokinetic parameters to achieve optimal doses and schedules . In rodents, human IgMs have an effective circulatory half-life of 11 h and a plasma clearance rate of 0.044 ml/min/kg . Studies of a new group of human monoclonal antibodies (hMAb) specific for Gram-negative bacteria and endotoxin revealed an IgM molecule, hMAb-10058, which, when purified from tissue culture medium, exhibited a suprisingly short circulatory lifetime in rodents . Investigations into possible explanations for this short circulatory half-life resulted in the development of a simple and efficient method for producing hMAbs in the immunodeficient NIH-3 mouse (bg x nu x XID) . This method of production of hMAb-10058 had dramatic effects on its half-life . Whereas hMAb-10058 produced in serum-free, defined medium had a clearance rate of 14.4 ml/min/kg and an effective half-life of 0.12 h, the same hMAb-10058 raised in mouse ascites had a decreased clearance rate of 0.092 ml/min/kg and an increased effective half-life of 12 h . This 100-fold enhancement of the hMAb's half-life was not affected by the purification process . Some potential molecular structures involved in the circulatory half-life of this hMAb are discussed.

Cancer Immunol Immunother, 1991, 33(5), 285 - 92
Comparative efficacy of liposomes containing synthetic bacterial cell wall analogues for tumoricidal activation of monocytes and macrophages; Utsugi T et al.; We examined the activation to the tumoricidal state of normal mouse peritoneal exudate macrophages, bone marrow macrophages, and human blood monocytes by liposomes containing either lipophilic muramyl tripeptide (CGP 19,835) or a new synthetic analogue of lipoprotein from gram-negative bacteria outer wall, CGP 31,362, or combinations of the two . The superiority of liposomes containing the synthetic lipopeptide over liposomes containing lipophilic muramyl tripeptide for in vitro activation of monocytes and macrophages was demonstrated in several experiments . First, liposome-CGP-19,835 activated monocytes only in the presence of interferon-gamma, whereas activation with liposome-CGP 31,362 was interferon-independent . Second, activation of both mouse macrophages and human blood monocytes by liposome-CGP 31,362 occurred at a lower liposomal concentration than that by liposome-CGP 19,835 . Third, monocytes incubated with liposome-CGP 31,362 released both tumor necrosis factor (TNF) and interleukin-1 activities, whereas monocytes treated with liposome-CGP 19,835 (in the absence of interferon-gamma) released only TNF activity . These data suggest that liposomes containing the synthetic lipopeptide CGP 31,362 are superior to liposomes containing CGP 19,835 for systemic activation of macrophages.

Int Arch Occup Environ Health, 1991, 62(8), 595 - 601
Relationship of airborne endotoxin and bacteria levels in pig farms with the lung function and respiratory symptoms of farmers; Heederik D et al.; Previous studies have demonstrated a high prevalence of respiratory and other symptoms and a decrement in lung function among pig farm workers, although the relationships with specific agents present in the work environment remain obscure . This study was therefore undertaken to investigate the relationship between symptoms, lung function and airborne endotoxin, ammonia and dust levels in piggeries . Information on symptoms, lung function, endotoxin, ammonia and dust levels was available for 183 pig farmers who worked in 136 farms . For 62 farms information was present on the levels of bacteria and gram-negative bacteria . For these 62 farms, endotoxin exposure measurements were taken in more than one stable . In general, no significant correlations were found between lung function and chronic respiratory symptoms, or dust and ammonia levels . The endotoxin concentration in stables was negatively related to most lung function variables, but only for the subgroup of 62 farmers was a statistically significant relationship found between endoxtoxin exposure and FEV1 . A borderline statistically significant and negative relationship was found between the endotoxin concentration and the FVC . Symptoms experienced during or shortly after work showed odds ratios larger than one with the levels of bacteria, gram-negative bacteria and endotoxin, indicating a positive relationship . No consistency in the relationship between symptoms and dust levels was found . The results suggest that endotoxins and (gram-negative) bacteria probably play an important role in the development of symptoms and lung function changes among pig farmers.

Eur Surg Res, 1991, 23(5-6), 309 - 16
Demonstration of an interaction between transferrin and lipopolysaccharide--an in vitro study; Berger D et al.; Transferrin is reported to be a major lipopolysaccharide binding protein of human plasma, at least in vitro . By use of the limulus-amebocyte-lysate test the influence of transferrin on endotoxicity was studied . In the absence of any other protein human iron-free transferrin was able to strongly enhance endotoxicity in a concentration-dependent manner . Similar results were obtained when transferrin was added to primarily heat-inactivated plasma . Even in this assay the endotoxin recovery increased when transferrin was exogenously added . On the other hand, transferrin inhibited endotoxicity when inactivation of the plasma samples was performed after the addition of endotoxin and transferrin . These results lead to the conclusion that transferrin in fact interacts with lipopolysaccharide in a biologically important manner . In order to achieve neutralization of endotoxin, however, other plasma constituents are needed . The hypothetical function of transferrin is possibly a disaggregation of lipopolysaccharide micelles, following the interaction between the two molecules . The present data should justify further studies in order to clarify a possible benefit of the substitution of transferrin during gram-negative sepsis.

J Egypt Public Health Assoc, 1991, 66(1-2), 79 - 95
Branhamella catarrhalis and respiratory tract infections; Nicolas GM et al.; Branhamella catarrhalis, a Gram negative diplococci, is gaining increasing recognition as a respiratory pathogen . In this study 40 sputum samples were collected from patients with acute or chronic lower respiratory tract infections and 15 samples from healthy controls . Each sample was examined for the isolation and identification of B . catarrhalis and other respiratory pathogens . From the control group 3 strains of B . catarrhalis were encountered: two of these were of low number in the collected sample and the third was found in a sample containing low number of leukocytes and more than 10 BSE cells/HPF which indicate that the sample was just saliva . From the cases of this study B . catarrhalis was isolated from 7 sputum samples . It was of the same frequency of isolation as the other known respiratory pathogens, more in old age, smokers and ex-smokers and all the strains were in mixed infections . B . catarrhalis isolated in this study were susceptible to cephalosporin regardless of the production of Beta-lactamase.

Vet Res Commun, 1991, 15(5), 341 - 62
Bacteraemia in man and animals: an overview; Vaid J; Bacteraemia signifies invasion of the bloodstream by bacteria . In most systemic infections in man and animals, bacteria enter the blood at some stage during the infection and are rapidly distributed throughout the body . A wide variety of organisms have been associated with bacteraemia . Prompt detection of the aetiological agents of bacteraemia is of prime importance in clinical microbiology . There are no defined recommendations for blood cultures in animals but both conventional and improved methods are available for detection of bacteraemia in man . The consequences of bacteraemia are as diverse as the potential aetiological agents . Monoclonal antibodies to the core glycolipid (lipid A) seems very promising for the treatment of bacteraemia and septic shock caused by Gram-negative bacteria in man and animals.

Crit Rev Biotechnol, 1991, 11(3), 277 - 95
Principles and biotechnological applications of bacterial ice nucleation; Margaritis A et al.; Certain aerobic, Gram-negative bacteria, including the epiphytic plant pathogen, Pseudomonas syringae, possess a membrane protein that enables them to nucleate crystallization in supercooled water . Currently, these ice-nucleating (IN) bacteria are being used in snow making and have potential applications in the production and texturing of frozen foods, and as a replacement of silver iodide in cloud seeding . A negative aspect of these IN bacteria is frost damage to plant surfaces . Thus, of the various types of biological ice nucleators, bacteria have been the subject of most research and also appear relevant to the anticipated practical uses . The intent of this review is to explain the identification and ecology of the ice-nucleating bacteria, as well as to discuss aspects of molecular biology related to ice nucleation and consider existing and potential applications of this unique phenomenon.

Microbiol Immunol, 1991, 35(8), 623 - 9
Electron microscopic studies on the in vitro proliferation of spotted fever group rickettsia isolated in Japan; Amano K et al.; Rickettsia was isolated from a patient with Japanese spotted fever, and its proliferation in cultured green monkey kidney cells was observed by electron microscopy . In the course of this study, we observed fusion of infected cells to uninfected cells which may be a way of spreading the rickettsiae from a cell to another . On the other hand, whirlpool-like, multilayer membranous structures, similar to the mesosomes of gram-negative bacteria, were sometimes seen in the rickettsial cells . The other profiles common to the other rickettsiae in spotted fever group were observed, such as the electron-lucent halo zone around the rickettsiae, and external fibrous materials on their surface, but intranuclear multiplication was rarely observed.

Lab Delo, 1991, (12), 49 - 51
{A method of electrophoretic differentiation of the genera of glucose-nonfermenting gram-negative bacteria}; Volchkevich ZhA et al.; Glucose nonfermenting gram-negative bacteria were electrophoretically typed for the extracellular protein spectra . The method permits differentiation on the generic level the cultures of such bacteria, characterized by atypical biochemistry, within 10 hours.

J Infect Dis, 1991 Jan, 163(1), 122 - 7
Immunization of mice with antibiotic-treated Escherichia coli results in enhanced protection against challenge with homologous and heterologous bacteria; Raponi G et al.; The murine immune response to Escherichia coli exposed to subminimal inhibitory concentrations of four antibiotics was investigated . Groups of mice were injected for 8 weeks with formalin-killed bacteria and subsequently challenged with 10 x LD50 of viable E . coli . Mice receiving saline only (controls) died within 24 h . The mortality of mice immunized with ciprofloxacin-treated E . coli was significantly lower than that of mice immunized with E . coli untreated or treated with other antibiotics . Sera from mice immunized with ciprofloxacin-treated bacteria showed better bacteriostatic capacity and enhanced production of antibodies that bound to homologous and heterologous lipopolysaccharide isolated from several smooth and rough gram-negative strains . The better protection observed in mice immunized with ciprofloxacin-treated E . coli was probably due to an enhanced production of antibodies to epitopes on lipopolysaccharide that became better exposed and so more accessible after treatment with ciprofloxacin.

J Immunol, 1991 Jan 1, 146(1), 327 - 31
The primary B cell response to the O/core region of bacterial lipopolysaccharide is restricted to the Ly-1 lineage; Su SD et al.; Experiments were performed to test the hypothesis that Ly-1 B cells respond to antigenic challenge with LPS from gram-negative bacteria . To perform these experiments, the splenic fragment culture system for the study of B cell precursors was used . We found that a significant number of anti-O/core, but not anti-lipid A, precursors expressed the lambda L chain . A restriction of the anti-LPS response to Ly-1 B cells was tested using a Ly-1 depletion protocol . We found that the anti-O/core antibody response was restricted to the Ly-1 B cell lineage . In contrast, conventional B cells, not Ly-1 B cells, respond to an antigenic challenge with lipid A . Our results further support the idea that the Ly-1 B cell lineage serves a direct role in protecting against certain bacterial infections.

Annu Rev Microbiol, 1991, 45, 383 - 415
Chaperone-assisted assembly and molecular architecture of adhesive pili; Hultgren SJ et al.; The assembly of bacterial pili as exemplified here by P and type 1 pili of E . coli is a complex process involving specific molecular interactions between structural and chaperone proteins . The assembly process occurs postsecretionally, i.e . after the subunits are translocated across the cytoplasmic membrane . In a single cell, hundreds of thousands of interactive subunits are typically surface localized and assembled into pili . Periplasmic chaperones are generally required to bind to the interactive subunits and partition them into assembly-competent complexes . The binding of the chaperone to the subunits apparently protects the interactive surfaces and prevents them from aggregating at the wrong time and place within the cell . Pili are most likely assembled into linear polymers that package into right-handed helices after their translocation through specific outer-membrane channels . Each pilus filament is a quaternary assembly of the structural subunit and several minor subunits including the adhesin moiety . Although the assembly and organization of P and type 1 pili are very similar, there are some notable differences . For example, the P pilus adhesin is located exclusively at the tips of the pilus filament and forms part of a morphologically distinct structure . In contrast, the adhesion moiety of type 1 pili is inserted into the pilus filament at intervals, but only the adhesin molecule exposed at the pilus tip is functional . The variability in isoreceptor recognition amongst P pili has been solely ascribed to structural differences in the respective adhesin molecules, whereas in type 1 pili, variability in binding specificity has been attributed to the pilus filament that influences the conformation of the adhesin moiety . Less is known about the structure or assembly of type 4 pili, which are a unique class of pili expressed by several different species of gram-negative bacteria . The phase variation of the pilC assembly gene in N . gonorrheae to the off state results in the accumulation of unassembled subunits toxic to the cells . This process exerts a strong selection pressure on the cells that triggers alterations in the pilin structural gene . Thus, antigenic variation of pili in this organism may be regulated at the level of assembly . Finally, the concept of periplasmic chaperones in postsecretional assembly is most likely a general phenomenon in the biology of gram-negative bacteria . The investigations of pilus assembly will continue to provide insight into the details of how macromolecular assembly reactions are coordinated in the bacterial cell and how the regulation of assembly genes can profoundly affect biological processes.

Eur J Surg, 1991 Jan, 157(1), 45 - 9
Ceftriaxone vs . ampicillin + metronidazole as prophylaxis against infections after clean-contaminated abdominal surgery; Luke M et al.; In a prospective, controlled, double-blind study, 496 patients undergoing abdominal surgery were given antibiotic prophylaxis with a single dose of either ceftriaxone or ampicillin + metronidazole . No significant intergroup difference was found between the respective overall rates of infectious complications (3.2% and 4.9%) . Analysis of the microbiologic findings showed incisional wound infections, mainly caused by gram-negative rods, to be more common in the ampicillin-metronidazole group, whereas deep wound infections were more frequent in the ceftriaxone group . It is concluded that ceftriaxone seems to be more efficient than ampicillin-metronidazole as prophylaxis against incisional wound infection, but should preferably be supplemented with an antianaerobic agent to prevent deep wound infections.

Rev Int Trach Pathol Ocul Trop Subtrop Sante Publique, 1991, 68, 63 - 73
{Tropical conjunctivitis: infectious etiology and validation of its clinical features}; Castan R et al.; 173 nontrachomatous conjunctivitis studied at the I.O.T.A . in Bamako, Mali, have shown a majority of bacterial aetiology, especially gram-negative . 1 out of 10 conjunctivitis was due to virus, mostly to adenovirus . 4% of the cases were due to Chlamydia Trachomatis . The try of validation of the clinical characters in comparison with the etiology has shown that Chemosis was an indicator of a bacterial conjunctivitis (OR = 2.4) and that the lack of purulent discharge was in connexion with the presence of a keratitis (OR = 7.7) . On the one hand the frequency of gram-negative bacteria, on the other hand the potential gravity of the conjunctivitis in tropical area, would justify the use of gentamycin at first in nontrachomatous conjunctivitis.

Acta Clin Belg, 1991, 46(6), 364 - 70
Fatal septicemia with Capnocytophaga canimorsus in a compromised host . A case report with review of the literature; Vanhonsebrouck AY et al.; Capnocytophaga canimorsus (DF-2) is a newly described gram-negative bacterium that can produce serious infections following dog bites in the immunocompromised host . We are reporting a case of C . canimorsus infection in an elderly patient with a history of chronic respiratory disease and alcohol abuse . We also give a review of the clinical spectrum of the infection, discuss the difficulty in establishing the diagnosis and the preferential treatment.

Med Oncol Tumor Pharmacother, 1991, 8(1), 15 - 21
Studies on the mechanism of synthesis and release of the procoagulant activity from leukaemic cells; Mohanty D et al.; The synthesis and release of procoagulant activity (PCA) from leukaemic leucocytes was studied in an in vitro culture system stimulated by endotoxin . Puromycin, actinomycin-D, vinblastine, colchicine, dibutyryl cyclic AMP and ouabain were added to the culture system to study some of the metabolic processes of these cells in relation to synthesis and release of PCA . It was found that production of PCA is an active process and depends on new protein synthesis . The release of PCA from cells can be inhibited by vinblastine, an inhibitor of microfilament and microtubules in the cell . The optimal release of PCA occurs at pH 7.2-7.4 at 37 degrees C and is not inhibited by the ATPase inhibitor ouabain . Dibutyryl cyclic AMP inhibits the release/synthesis of PCA . Gram negative septicaemia and endotoxinaemia are capable of increased production and release of PCA from leukaemic cells and could contribute to the coagulation failure seen in this disease.

Blood, 1990 Dec 15, 76(12), 2520 - 6
Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways; van Deventer SJ et al.; Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2 ng/kg body weight) in six healthy subjects to investigate the early kinetics of cytokine release in relation to the development of clinical and hematologic abnormalities frequently seen in gram-negative septicemia . The plasma concentration of tumor necrosis factor (TNF) increased markedly after 30 to 45 minutes, and reached a maximal level after 60 to 90 minutes . In each volunteer, the initial increase of plasma interleukin 6 (IL-6) concentrations occurred 15 minutes after the initial TNF increase, and maximal IL-6 concentrations were reached at 120 to 150 minutes . A transient increase in body temperature and pulse rate occurred simultaneously with the initial TNF and IL-6 increases, whereas a significant decrease in blood pressure occurred after 120 minutes . These changes were proportional to the changes in TNF and IL-6 concentrations . Coagulation activation, as assessed by a rise of prothrombin fragments and thrombin-antithrombin III complexes, was noted after 120 minutes, in the absence of activation of the contact system . A two- to sixfold increase in the concentrations of tissue plasminogen activator (t-PA) and von Willebrand factor antigen indicated endothelial cell activation . This increase started at 120 and 90 minutes, respectively . The release of t-PA coincided with activation of the fibrinolytic pathway, as measured by plasmin-alpha 2-antiplasmin complexes . The fibrinolytic activity of t-PA was subsequently offset by release of plasminogen activator inhibitor, observed 150 minutes after the endotoxin injection, and reaching a peak at 240 minutes . No complement activation was detected . These results show that in humans endotoxin induces an early, rapidly counteracted fibrinolytic response, and a more long-lasting activation of thrombin by a mechanism other than contact system activation . In addition, our data suggest that endotoxin-induced leukopenia and endothelial cell activation are mediated by TNF.

Nature, 1990 Dec 6, 348(6301), 550 - 2
Interleukin-1 receptor antagonist reduces mortality from endotoxin shock; Ohlsson K et al.; About five out of 1,000 patients admitted to hospital develop bacterial sepsis leading to shock, the mortality rate for which is high despite antibiotic therapy . The infection results in hypotension and poor tissue perfusion, and eventually leads to the failure of several organ systems . Bacterial endotoxin is thought to be the direct cause of shock in Gram-negative sepsis, because it can cause shock in animals, and antibodies against endotoxin prevent Gram-negative shock in animals and in humans . But, the symptoms of septic shock are the result of the actions of host cytokines induced by the endotoxin . The cytokine interleukin-1 has been implicated as an important mediator of septic shock because it can induce tachycardia and hypotension and act synergistically with tumour necrosis factor to cause tissue damage and death . We now report that a specific interleukin-1 receptor antagonist reduces the lethality of endotoxin-induced shock in rabbits, indicating that interleukin-1 does indeed play an important part in endotoxin shock.

Ann Pediatr (Paris), 1990 Dec, 37(10), 665 - 7
{Capnocytophaga septicemia during bone marrow transplantation . Apropos of 2 cases}; Vanlemmens P et al.; Two cases of septicemia due to Capnocytophaga in pediatric bone marrow recipients are reported . These gram negative rods, which are part of the normal buccal flora, cause periodontitis and localized or systemic infections, usually in immunocompromised hosts . Severe, prolonged neutropenia and mucitis due to chemotherapy and/or radiotherapy are risk factors for this opportunistic infection . Recovery can be achieved with most of the drug combinations including a beta-lactam used in hematology.

Clin Exp Immunol, 1990 Dec, 82(3), 515 - 21
Lipopolysaccharide from gram-negative bacteria enhances polyclonal B cell activation and exacerbates nephritis in MRL/lpr mice; Cavallo T et al.; Depletion of B cells in mice bearing the lymphoproliferation (lpr) gene reduces lymphoproliferation and polyclonal B cell activation (PBA) and attenuates mononuclear cell vasculitis . We sought to verify whether the obverse was true, i.e . whether enhancement of B cell activity might exacerbate the nephritis of MRL/lpr (MRL) mice, a lupus-prone strain . The experimental approach was designed to address three questions: whether naturally occurring PBA in MRL mice could be further enhanced; whether enhanced PBA would exacerbate nephritis; and whether the mechanism of nephritis exacerbation involved interference with mononuclear phagocyte system (MPS) function . To enhance B cell activity, we injected MRL mice with lipopolysaccharide (LPS) from Gram-negative bacteria, a potent B cell activator . To determine whether nephritis was exacerbated, we performed immunopathologic studies and tests of renal function . To verify whether nephritis exacerbation involved impairment of MPS function, we probed the kinetics of immune complex removal from the circulation, their uptake by the liver and spleen, and their localization in kidney tissue . The results indicate that in MRL mice: (i) spontaneous PBA can be enhanced by LPS; (ii) enhancement of PBA by LPS exacerbates nephritis; and (iii) the MPS is already saturated, presumably due to excessive production of endogenous immune complexes . Thus, further increase in immune complex formation due to enhanced PBA by LPS results in increased localization of immune complexes in kidneys and exacerbated nephritis.

J Trauma, 1990 Dec, 30(12 Suppl), S189 - 92
A new model of macrophage stimulation by bacterial lipopolysaccharide; Ulevitch RJ et al.; Infection occurring in patients suffering from severe trauma or burns often leads to hypotension, disseminated intravascular coagulation, multiorgan failure, and death . These latter pathophysiologic changes often are associated with Gram-negative sepsis and endotoxemia . Substantial progress has been made in understanding the effector mechanisms for endotoxin (LPS) action with the recognition of the importance of LPS-inducible products of cells of monocytic lineage in mediating LPS-induced injury . Here we will review recent evidence that supports a model for monocyte/macrophage activation by LPS that involves a plasma protein known as lipopolysaccharide binding protein (LBP) and the monocyte differentiation antigen, CD14.

Infect Immun, 1990 Dec, 58(12), 3934 - 40
In vitro sensitivity of oral, gram-negative, facultative bacteria to the bactericidal activity of human neutrophil defensins; Miyasaki KT et al.; Neutrophils play a major role in defending the periodontium against infection by oral, gram-negative, facultative bacteria, such as Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga spp . We examined the sensitivity of these bacteria to a mixture of low-molecular-weight peptides and highly purified individual defensin peptides (HNP-1, HNP-2, and HNP-3) isolated from human neutrophils . Whereas the Capnocytophaga spp . strains were killed significantly by the mixed human neutrophil peptides, the A . actinomycetemcomitans and E . corrodens strains were resistant . Killing was attributable to the defensins . The bactericidal activities of purified defensins HNP-1 and HNP-2 were equal, and both of these activities were greater than HNP-3 activity against strains of Capnocytophaga sputigena and Capnocytophaga gingivalis . The strain of Capnocytophaga ochracea was more sensitive to defensin-mediated bactericidal activity than either C . sputigena or C . gingivalis was . The three human defensins were equipotent in killing C . ochracea . C . ochracea was killed under aerobic and anaerobic conditions and over a broad pH range . Killing was most effective under hypotonic conditions but also occurred at physiologic salt concentrations . We concluded that Capnocytophaga spp . are sensitive to oxygen-independent killing by human defensins . Additional studies will be required to identify other components that may equip human neutrophils to kill A . actinomycetemcomitans, E . corrodens, and other oral gram-negative bacteria.

Am J Respir Cell Mol Biol, 1990 Dec, 3(6), 563 - 70
Fibronectin is not detectable on the intact buccal epithelial surface of normal rats or humans; Mason CM et al.; Fibronectin (FN) has been postulated to prevent gram-negative bacillary (GNB) colonization of the oropharynx by covering epithelial cell GNB receptors . We investigated the distribution of FN along the luminal surface of oropharyngeal epithelium in animals and humans . Examination of buccal epithelial biopsies obtained from normal rats revealed no luminal surface FN by either immunofluorescent or immunoperoxidase staining . Extraction of epithelial surface proteins and quantitation of FN by rocket immunoelectrophoresis and electrophoretic transfer to nitrocellulose followed by immunologic detection also detected no FN from normal animals' oropharyngeal biopsies . Buccal epithelial biopsies from three normal humans were examined for FN using electrophoretic transfer to nitrocellulose followed by immunologic detection, and no FN was demonstrable . Our results suggest that FN is not present on the oral epithelial surface of healthy rodents or humans, and that FN may not be involved in the pathogenesis of bacillary colonization.

Crit Care Med, 1990 Dec, 18(12), 1311 - 5
Initial evaluation of human monoclonal anti-lipid A antibody (HA-1A) in patients with sepsis syndrome; Fisher CJ Jr et al.; HA-1A, a human monoclonal immunoglobulin M antibody that binds specifically to the lipid A domain of endotoxin, was administered to septic patients to evaluate the safety, pharmacokinetics, and immunogenicity of the antibody . Thirty-four patients received a single infusion of either 25 mg, 100 mg, or 250 mg, and were followed clinically for 14 to 21 days after treatment . HA-1A serum levels were measured before infusion and frequently after infusion with a radiometric assay . A one-compartment pharmacokinetic model was fit to the measured serum levels, and accurately described the changes in HA-1A level over time in each dose group (r2 = .99) . The mean +/- SEM apparent volume of distribution of HA-1A was 48.5 +/- 4.5 ml/kg, and the mean serum clearance was 2.8 +/- 0.4 ml/kg.h . The mean serum half-life of HA-1A was 15.9 +/- 1.5 h . The mean serum level one hour after a 100-mg dose was 33.2 +/- 2.4 micrograms/ml, and the mean concentration 24 h later was 9.1 +/- 1.6 micrograms/ml . The dose administered and presence of Gram-negative bacterial infection did not significantly influence the volume of distribution or serum clearance . No adverse reactions to HA-1A were observed, and no antibodies against HA-1A were detected in any patient . These data indicate that the pharmacokinetics of HA-1A are well described by a one-compartment pharmacokinetic model, and that HA-1A is safe and nonimmunogenic in patients with sepsis.

Clin Sci (Lond), 1990 Dec, 79(6), 619 - 23
Endothelin immunoreactivity in mice with gram-negative bacteraemia: relationship to tumour necrosis factor-alpha; Takahashi K et al.; 1 . To investigate the role of endothelin in Gram-negative bacteraemia and the possible involvement of tumour necrosis factor-alpha in its pathophysiology, we measured plasma and tissue (lung, kidney and spleen) immunoreactive endothelin levels in Gram-negative bacteraemic mice, with and without passive immunization by anti-(tumour necrosis factor-alpha) antibody . 2 . Plasma immunoreactive endothelin levels were greatly increased after the Escherichia coli injection . Pretreatment with anti-(tumour necrosis factor-alpha) antibody did not suppress elevated plasma immunoreactive endothelin levels (P greater than 0.1) . 3 . Lung tissue immunoreactive endothelin levels in mice were increased 16 h after the E . coli injection and were not affected by prior passive immunization with anti-(tumour necrosis factor-alpha) antibody . Immunoreactive endothelin in spleen and kidney was undetectable (less than 34 fmol/g wet weight) . 4 . Injection of rMu tumour necrosis factor-alpha into mice did not increase plasma immunoreactive endothelin levels . 5 . Antibody to endothelin given 30 min after a 90% lethal dose challenge with E . coli did not affect mortality . 6 . We conclude that the rise in plasma and tissue endothelin that occurs in Gram-negative bacteraemia is independent of tumour necrosis factor-alpha.

Mol Microbiol, 1990 Dec, 4(12), 2019 - 25
TonB and the gram-negative dilemma; Postle K; TonB protein serves as an energy transducer to couple cytoplasmic membrane energy to high-affinity active transport of iron siderophores and vitamin B12 across the outer membranes of Gram-negative bacteria . The biochemical mechanism of the energy transduction remains to be determined, but important details are already known . TonB is targeted to and anchored in the cytoplasmic membrane by a single membrane-spanning domain and spans the periplasm to physically interact with outer-membrane receptors of the transport ligands . TonB-dependent energy transduction is modulated by ExbB protein, which stabilizes TonB, and possibly by several other proteins including ExbC, ExbD, and TolQ . TonB has a relatively short functional half-life that is accelerated when rates of active transport across the outer membrane are increased . A model that incorporates this information, as well as some tempered speculation, is presented.

An Med Interna, 1990 Dec, 7(12), 613 - 7
{Histopathologic changes associated with the presence of Helicobacter pylori in antral mucosa}; de Portugal J et al.; Helicobacter pylori is a gram negative bacteria which has recently been associated to tissular changes of the upper digestive tract, however, the causal role has not yet been determined . Of 150 patients studied, 63 had tissular changes associated to Helicobacter pylori (Hp), 8 had Hp without tissular related changes (of whom 3 suffered bulbar ulcus and 1 gastric ulcus); the rest of the patients had hiatus hernia associated to distal esophagitis or pyloric stenosis; and only one patient was found to have normal tissue . A clear associated to distal esophagitis or pyloric stenosis; and only one patient was found to have normal tissue . A clear association between Hp and chronic or atrophic gastritis was determined, but no association was found between Hp and gastric cancer.

Prakt Zubn Lek, 1990 Dec, 38(10), 289 - 93
{Bacterial contamination of the atmosphere of the dental surgery during preparation with turbin equipment . 2 . Microbiological examination of water of stomatological sets}; Dziedzic I et al.; Water forms a substantial part of aerosol particles formed during preparation with turbin equipment . The authors assessed therefore before aerobiological examination of the atmosphere of the dental surgery which will be the subject of part III whether the water used for cooling of dental sets is contanined by pathogenic bacteria . Microbiological examination of water specimens of the cooling system of four dental sets of two types revealed only the presence of Baccilus subtilis and Gram-negative rods . The results of aerobic cultivation of all 48 water specimens were identical . The authors did not find a difference between water samples at the beginning and at the end of working hours nor between specimens collected on different days . The measurements were made as part of a student contest and the results were presented at a student conference at the Faculty of General Medicine, Charles University Prague and in a nation-wide contest in Kosice.

Arch Mal Coeur Vaiss, 1990 Dec, 83(14), 2053 - 9
{Infectious endocarditis in the University Hospital Center of Brazzaville . A study of 32 cases}; Bouramoue C et al.; Thirty-eight cases of infective endocarditis (IE) were observed between 1976 and 1989 (1.3% of all cardiac disease) . Thirty two cases were retained for study based on Von Reyn's criteria: 28 native valve endocarditis (27 left and 1 right heart valves) of which 18 occurred on previously undiseased valves (56.3%); 4 cases of left heart prosthetic valve endocarditis . The average age of the patients was 27.5 +/- 14 years and the group comprised 24 women and 8 men (p less than 0.001) . Blood cultures were negative in 13 cases, revealed a Gram negative pathogen in 8 cases, a streptoccocus in 3 cases . Blood cultures were not performed in 2 cases . The IE was acute in 18 cases (56.7%) and subacute in 14 cases (43.7%) . The dominant clinical signs were of massive and sometimes acute valvular regurgitation (mitral: 21 cases; aortic: 10 cases; mitral and aortic: 3 cases; tricuspid: 1 case) . Twenty-six patients had cardiac failure (81.2%): LVF: 15 cases, congestive cardiac failure: 10 cases, RVF: 1 case . The other complications were embolic: cerebral (3 cases), mesenteric (1 case), pulmonary (4 cases) . Antibiotic therapy was prescribed in all patients; surgery was required in 9 cases . There were 12 fatalities (37.5%), 10 in the medically treated group and 2 in the surgical group (p less than 0.05) . The results show that the prognosis of IE in underdeveloped regions remains poor . Effective strategies of early diagnosis and treatment are urgently required to reduce the high mortality . Prophylaxis of IE should commence with measures to counter the portals of entry of the pathogens and the valvular sequellae of acute rhumatic fever.

Am J Infect Control, 1990 Dec, 18(6), 365 - 70
A prospective study of nosocomial infections in cardiac surgery patients in China; Li LY et al.; A prospective survey of postoperative nosocomial infections (NI) in cardiac surgery was carried out in a cardiovascular specialty hospital in Beijing, China . During the period from December 1986 to December 1987, 1208 cardiovascular surgery patients were surveyed for NI . The overall incidence of NI was found to be 7.5% . The incidence of lower respiratory tract and wound infections were 4.5% and 2.9%, respectively . These two kinds of infection accounted for 78.1% of the total infections . After effective control measures were taken at the end of the first 6 months (December 1986 to May 1987) of the study, the incidence fell from 10.6% to 5.1% in the next 7-month period (June to December 1987) . The pathogens causing NI were mostly gram-negative bacteria, and they were mainly opportunistic . The contribution of fungal infection was significant in the hospitals . The majority of the pathogenic isolates were highly resistant to the antibiotics commonly used in the hospital.

Tijdschr Kindergeneeskd, 1990 Dec, 58(6), 200 - 3
{Cat-scratch disease}; Haraldsson A et al.; Cat scratch disease is an infectious disorder caused by a Gram-negative bacterium . The classical form is heralded by a scratch, subsequently red papules develops at the place of the inoculation . After an incubation period of one to two weeks lympadenopathy without lymphangitis occurs, with tender, red, warm and indurated skin as well as fever and general malaise . In the atypical form, different organs may be involved . Specific treatment is not indicated and the overall prognosis is good . The diagnoses of cat scratch disease can be sustained by a skin test.

Microbiol Rev, 1990 Dec, 54(4), 331 - 41
TraT lipoprotein, a plasmid-specified mediator of interactions between gram-negative bacteria and their environment; Sukupolvi S et al.; The TraT protein is a cell-surface-exposed, outer membrane lipoprotein specified by large, usually conjugative, F-like plasmids . Two biological activities have been associated with the protein: (i) prevention of self-mating of cells carrying identical or closely related conjugative plasmids, by blocking the formation of stable mating aggregates; and (ii) resistance to the bactericidal activities of serum, possibly by inhibiting the correct assembly or efficient functioning of the terminal membrane attack complex of complement . The protein therefore interacts not only with components of the outer membrane but also with specific external agents . In conjugative plasmids the traT gene lies within the region necessary for the conjugal transfer of DNA (tra), although its expression is not necessarily dependent on the expression of other tra genes . Recently, however, the gene has been discovered in isolation from other tra genes in nonconjugative virulence-associated plasmids, providing further evidence that the TraT protein may have a role in pathogenesis . The nucleotide sequences of several traT genes have been determined, and comparison of the corresponding amino acid sequences suggests that a central region of five amino acid residues flanked by hydrophobic domains determines the specificity of the protein in surface exclusion . Additionally, studies of mutants with different amino acid alterations within the hydrophobic domains have shown that insertion of charged residues disrupts normal outer membrane integrity . This review considers our current knowledge of the distribution, structure, and biological role(s) of the protein . Recent applications of the protein in studies of the unusual permeability properties of the outer membrane and for the transport of foreign antigenic determinants to the bacterial cell surface are also discussed.

Mol Gen Genet, 1990 Dec, 224(3), 421 - 30
Characterization of three different nitrogen-regulated promoter regions for the expression of glnB and glnA in Azospirillum brasilense; de Zamaroczy M et al.; The complete nucleotide sequence of the open reading frame (ORF) located upstream of the glnA structural gene for glutamine synthetase (GS) in Azospirillum brasilense Sp7 was determined . This ORF, which codes for a 12 kDa protein, was identified as glnB, the structural gene for the PII protein, a component of the adenylylation cascade involved in the regulation of GS activity in some gram-negative bacteria . Transcription analysis and mRNA mapping of glnB and glnA of A . brasilense was performed with bacteria grown under different physiological conditions . The glnA gene can be transcribed either as a glnB-A mRNA of 2.4 kb or as a glnA mRNA of 1.5 kb . Differential expression of the two mRNAs was found to depend on the nitrogen source . The glnB-A mRNA was the major transcript under nitrogen fixation conditions, while the synthesis of the glnA mRNA was almost completely abolished . The glnA mRNA was predominantly produced in NH4(+)-containing medium . Transcription start site analysis revealed the presence of three different types of nitrogen-regulated promoters . GlnB-A mRNA was transcribed selectively from tandem promoters . One of them is similar to the NtrA-dependent promoter and the other to the Escherichia coli sigma 70 promoter . The synthesis of glnA mRNA was regulated by a promoter, which was repressed (or non-activated) only under conditions of nitrogen fixation, when moleuclar nitrogen was the sole nitrogen source . The transcriptional initiation site in front of glnA is not preceded by a canonical E . coli sigma 70 promoter . A sequence reminiscent of the NtrA-dependent promoter consensus, except for a fundamental mismatch, was found at positions -33 to -21 . This sequence overlapped a putative "weak" NtrC-binding site, similar to those identified in enteric bacteria . From these results, it is postulated that glnA mRNA is controlled by a novel type of nitrogen-regulated promoter.

J Am Vet Med Assoc, 1990 Nov 15, 197(10), 1359 - 60
Suspected actinobacillosis manifested by facial enlargement in a heifer; Anderson KL et al.; Actinobacillosis was the suspected cause of severe, bilateral facial enlargement of 8 months' duration in a 2.5-year-old Holstein heifer . Serum protein electrophoresis revealed a polyclonal gammopathy . Necropsy findings indicated that facial swelling was caused by fibrosis between the skin and underlying bone . Lesions were characterized microscopically by scattered pyogranulomas containing eosinophilic, club-like colonies surrounding gram-negative bacterial rods . The lesion was compatible with diagnosis of actinobacillosis . It is unusual for severe bilateral facial enlargement to be associated with actinobacillosis.

J Med Entomol, 1990 Nov, 27(6), 1050 - 61
Prevalence and biology of endosymbionts of fleas (Siphonaptera: Pulicidae) from dogs and cats in Alachua County, Florida; Beard CB et al.; A study was conducted to determine the prevalence and biology of endosymbionts in local populations of fleas collected from dogs and cats in Alachua Co., Florida . Four hundred three Ctenocephalides felis (Bouche), 194 Pulex simulans Baker, and 44 Echidnophaga gallinacea (Westwood) were examined . Fleas were collected from 52 dogs and 51 cats . From 1 to 20 fleas were dissected from each host . A variety of microorganisms and metazoa was observed, including a baculovirus, gram-negative bacteria, rickettsia-like organisms, amoebae, trypanosomatid flagellates, cephaline gregarines, and microsporidia . Microfilariae of the dog heartworm, Dirofilaria immitis, entomophilic nematodes, and metacestodes of the tapeworm Dipylidium caninum were also observed.

J Reprod Med, 1990 Nov, 35(11 Suppl), 1082 - 90
Cefmetazole and cefonicid . Comparative efficacy and safety in preventing postoperative infections after vaginal and abdominal hysterectomy; Roy S et al.; A single 1-g dose of cefmetazole was compared with a single 1-g dose of cefonicid for prophylaxis in vaginal and abdominal hysterectomy to determine their efficacy and safety . The antibiotics were administered intramuscularly 15-90 minutes before the incision was made . Cefmetazole and cefonicid had similar activity against most of the aerobic organisms recovered, but cefmetazole was significantly more active against anaerobic gram-negative microorganisms . The patterns of regrowth of vaginal flora were similar in the two treatment groups . Patient demographic characteristics and surgical procedures were similar in both groups . The difference in primary prophylactic failure (e.g., cuff cellulitis) with the two study drugs (1 of 53 {1.9%} with cefmetazole and 2 of 28 {7.1%} with cefonicid) did not reach statistical significance, and the results were similar for the two routes of hysterectomy . Cefmetazole, at a dose of 1 g intramuscularly preoperatively, is a safe and effective agent for prophylaxis during hysterectomy.

J Membr Biol, 1990 Nov, 118(2), 161 - 70
Pore formation by complement in the outer membrane of gram-negative bacteria studied with asymmetric planar lipopolysaccharide/phospholipid bilayers; Schroder G et al.; The interaction of complement with an asymmetric planar lipopolysaccharide/phospholipid bilayer system as a model for the lipid matrix of the outer membrane of Gram-negative bacteria has been studied . The addition of whole human serum to the aqueous solution at the lipopolysaccharide side of the asymmetric membrane resulted in a rapid increase of the bilayer conductance in discrete steps, indicating the formation of transmembrane pores, which were not observed in the case of pure phospholipid membranes . The amplitudes of the discrete conductance steps varied over a range of more than one order of magnitude . The mean single step conductance was (0.39 +/- 0.24) nS for a subphase containing (in mM): 100 KCl, 5 MgCl2 and 5 HEPES buffer . The steps were grouped into bursts of typically 9 +/- 3 events per burst and the conductance change within one burst was (8.25 +/- 4.00) nS . The pore-forming activity of serum at the asymmetric membrane system was independent of the presence of specific antibodies against the lipopolysaccharide but was dependent on calcium ions . Furthermore, the pore-forming activity required complement component C9 . A model for the mode of pore formation by complement is proposed: The complement pore is generated in discrete steps by insertion of C9 monomers into the membrane and their irreversible aggregation to water-filled channels with a diameter of approximately 7 nm assuming a circular geometry.

Ann Surg, 1990 Nov, 212(5), 581 - 91
Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections; Solomkin JS et al.; We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections . We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection . Two hundred ninety patients were enrolled, of whom 162 were evaluable . Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both) . Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043) . The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018) . This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement . Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram-negative organisms . For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days . For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days . This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen.

Metabolism, 1990 Nov, 39(11), 1151 - 7
Altered ketone body metabolism during gram-negative sepsis in the rat; Lanza-Jacoby S et al.; To investigate why blood ketone bodies are depressed during sepsis, the production and utilization of ketone bodies was studied in fasted control, fasted, Escherichia coli-treated, fed control, and fed E coli-treated rats . Gram-negative sepsis was induced by intravenous (IV) injection of 8 x 10(7) live colonies of E coli per 100 g body weight . Food was removed from the fasted rats after E coli injection . Fed rats were infused intragastrically with a nutritionally adequate diet for 5 days before inducing sepsis . Twenty-four hours after E coli injection, blood ketone bodies were reduced in fasted septic rats and fed septic rats compared with their respective control rats . Ketogenesis and oxidation of labeled palmitate was not altered in hepatocytes from fasted E coli-treated rats . Yet, ketogenesis declined significantly in hepatocytes from fed E coli-treated rats . Oxidation of labeled palmitate was also significantly reduced in hepatocytes from fed E coli-treated rats . Utilization of ketone bodies as measured by the incorporation of {3-14C}beta-hydroxybutyrate into CO2, increased over threefold in the diaphragm, 12% in the heart, and 19% in the kidneys from the fasted E coli-treated rats . In the fed state, incorporation of {3-14C}beta-hydroxybutyrate into CO2 was elevated fivefold in the heart, fourfold in the diaphragm, and over threefold in the kidneys from the septic rats . These results suggest that in the fasted state, plasma ketone bodies remain low during gram-negative sepsis because peripheral tissues use more ketone bodies and because liver ketogenesis is not increased to compensate for the increased utilization . In the fed state, the reduction in blood ketone bodies appears to be attributed to both impaired ketogenic capacity and increased peripheral utilization.

J Thorac Cardiovasc Surg, 1990 Nov, 100(5), 777 - 80
Endotoxins in cardiopulmonary bypass; Nilsson L et al.; Endotoxins are biologically active substances derived from the cell wall of degraded gram-negative bacteria . Since sterile water may also contain large amounts of endotoxins, these are easily introduced into the manufacturing processes of technical medical material, such as the extracorporeal components used in cardiopulmonary bypass . In hemodialysis, the presence of endotoxins has been related to untoward effects in patients . Using the limulus amebocyte lysate test, we determined the serum concentration of endotoxin in 42 patients undergoing coronary bypass operations . The values increased during cardiopulmonary bypass, exceeding the normal range of 0 to 20 ng/L in 10 patients with a maximum of 82 ng/L, which probably indicates endotoxin release from the extracorporeal equipment . We found no obvious relation to postoperative morbidity . The endotoxin levels of this study are considerably lower than those reported in two other studies of patients having cardiopulmonary bypass . This might be due to less intraoperative contamination but possibly also to differences in analytic methods.

J Immunol, 1990 Nov 1, 145(9), 2994 - 3001
Analysis of the immune response to lipopolysaccharide . Existence of an interspecies cross-reactive idiotype associated with anti-lipid A antibodies; Su SD et al.; LPS is the major surface glycolipid on gram-negative bacteria . In this work, we have idiotypically characterized the antibody response against LPS in different species . To do this, we have produced mAb against LPS . Binding of many of these antibodies to LPS could be inhibited by LPS and lipid A, indicating that the monoclonals are specific for lipid A, the toxic moiety of the LPS molecule . One anti-lipid A antibody, IC9, proved protective against gram-negative bacteremia and endotoxic shock in murine protection models . We generated anti-idiotypic antibodies against IC9 . The binding of several of these anti-Id to IC9 was specifically inhibited by lipid A . We used these anti-Id to characterize the anti-LPS response, and the results revealed that the IC9 Id is conserved in different species . The importance of an interspecies cross-reactive Id in the response to endotoxin and its relevance in vaccine development for septic shock are discussed.

Arch Intern Med, 1990 Nov, 150(11), 2357 - 60
Acute renal failure in obstructive jaundice in cholangiocarcinoma; Mairiang P et al.; This study was aimed at defining the natural history of renal failure in obstructive jaundice due to cholangiocarcinoma, which is an important health problem in northeastern Thailand . Sixty-four patients among a total of 130 patients with obstructive jaundice secondary to cholangiocarcinoma who developed acute renal failure were studied retrospectively . Analysis was made with respect to clinical features, laboratory findings, and outcome . The development of renal failure before surgery was observed in all patients . It was nonoliguric in 80% and was associated with severe jaundice, gram-negative infection (42%), hypotension (31%), hypoproteinemia (30%), hyponatremia (56%), and hypokalemia (63%) . The mean duration of renal failure was 2 weeks . All patients underwent surgery for the relief of jaundice . Seventy-seven percent of the patients survived and had recovery of renal function after the relief of jaundice . Twenty-three percent of the patients died of infection . Clinical data highlight the higher serum bilirubin levels and the frequent occurrence of hyponatremia, hypokalemia, and hypotension in renal failure . Their possible roles in contributing to the development of renal failure are discussed.

Am Rev Respir Dis, 1990 Nov, 142(5), 1073 - 8
Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence; Zheng H et al.; Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS . Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo . We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation . We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN . A 51Cr release assay was used to measure EC damage . Further, we investigated PMN function in response to TNF by measuring chemiluminescence . Agents that attenuate EC damage and PMN activation were evaluated in the above assays . Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury . Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05) . Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN . Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05) . We conclude that TNF causes EC damage and PMN increase this damage . Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN . In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence . Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.

J Bacteriol, 1990 Nov, 172(11), 6204 - 16
Genetic characterization of the stabilizing functions of a region of broad-host-range plasmid RK2; Roberts RC et al.; One of the regions responsible for the stable inheritance of the broad-host-range plasmid RK2 is contained within the PstI C fragment, located from coordinates 30.8 to 37.0 kb (P.N . Saurugger, O . Hrabak, H . Schwab, and R.M . Lafferty, J . Biotechnol . 4:333-343, 1986) . Genetic analysis of this 6.2-kb region demonstrated that no function was present that stabilized by selectively killing plasmid-free segregants . The sequence from 36.0 to 37.0 kb mediated a twofold increase in plasmid copy number, but this region was not required for stabilization activity . The PstI C fragment was shown to encode a multimer resolution system from 33.1 to 35.3 kb . The resolution cis-acting site was mapped to 140 bp, sequenced, and observed to contain two directly repeated sequences of 6 and 7 bases and two perfect inverted repeats of 6 and 8 bases . The trans-acting factor(s) was mapped and functionally determined to encode a resolvase capable of catalyzing recombination at high frequency between cis-acting sites in either direct or inverted orientation . Multimer resolution alone did not account for complete plasmid stabilization by the PstI C fragment, since removal of regions adjacent to the 35.3-kb border of the minimal mrs locus dramatically reduced stabilization . The minimal region required for complete stabilization, from 32.8 to 35.9 kb, was capable of fully stabilizing plasmids independently of the replicon or the recA proficiency of the host . Stabilization activity was also fully expressed in several diverse gram-negative bacteria, whereas the F plasmid par locus functioned only in Escherichia coli . On the basis of these observations, we conclude that under the growth conditions used, the minimal stabilization locus encodes both an mrs activity and a stabilization activity that has the properties of a par locus.

New Biol, 1990 Nov, 2(11), 946 - 56
The hok killer gene family in gram-negative bacteria; Gerdes K et al.; The seven members of the hok killer gene family in Gram-negative bacteria are described here . The members of this gene family have been sequenced and include hok/sok from plasmid R1, flm and srnB from plasmid F, pnd from plasmids R483 and R16, and gef and relF, which are located on the Escherichia coli chromosome . The killer proteins encoded by these loci are highly toxic polypeptides of 50 to 52 amino acids . The proteins kill the cells from the inside by interfering with a vital function in the cell membrane . On the basis of their relatedness, the killer proteins and their corresponding loci are divided into four subfamilies . The members of one subfamily, hok/sok and flm, mediate plasmid maintenance by killing plasmid-free cells . The pnd and srnB subfamilies were discovered through their abilities to cause membrane damage and degradation of stable RNA . gef and relF, which constitute the chromosomal subfamily, were found because of their sequence similarity at the DNA and protein levels with other members of the hok gene family . However, no function has been described for the proteins belonging to this subfamily . Although the four subfamilies are distantly related in terms of DNA and protein sequence similarity, the overall genetic organization of the different loci has been well conserved during evolution . The expression of all of the members of the hok gene family is regulated post-transcriptionally . Thus, the expression of the hok and flm genes is regulated by small antisense RNAs that inhibit the translation of the stable hok and flm mRNAs . On the basis of structural and functional similarities, we suggest that each of the related plasmid-encoded killer genes is regulated by antisense RNAs . The conservation of this widespread gene family in Gram-negative bacteria suggests that the genes are important to the genomes that carry them.

Rev Clin Esp, 1990 Nov, 187(7), 321 - 4
{A microbiological and clinical study of 57 cases of spontaneous bacterial peritonitis in liver cirrhosis patients}; Saez-Royuela F et al.; We studied fifty seven episodes of cirrhotic spontaneous bacterial peritonitis in order to know its microbiological, clinical and evolutive characteristics . One third of the patients had presented some previous peritonitis episodes . Ninety three percent of the patients referred some symptoms at time of diagnosis . Ascitic fluid Gram stain showed the presence of bacteria in 72% of the samples . Culture of ascitic fluid was positive for a single microorganism in 50 cases (88%) . Seventy seven percent of microorganisms were Gram negative being Escherichia Coli in 63% of cases . Hemoculture was positive in 68% of cases with an almost complete correspondence with germs found in ascites . Seventy four percent of patients presented some complication throughout their hospital stay being the most frequent renal failure (49%) and encephalopathy (46%) . Sixty three percent of patients died being the mortality rate higher amongst the older patients and amongst those who did not present neither high temperature or peritonism, or those who developed some complication.

Nippon Saikingaku Zasshi, 1990 Nov, 45(6), 903 - 11
{Development of an endotoxin-specific Limulus amebocyte lysate test blocking beta-glucan-mediated pathway by carboxymethylated curdlan and its application}; Tsuchiya M et al.; We developed a simple new endotoxin-specific assay method that uses Limulus amebocyte lysate (LAL) containing a sufficient amount of a water-soluble (1----3)-beta-D-glucan derivative as a blocker of the (1----3)-beta-D-glucan-mediated coagulation pathway . The addition of 0.1 mg/ml or more of carboxymethylated (1----3)-beta-D-glucan completely blocked the activation of LAL by (1----3)-beta-D-glucan itself . The assay of endotoxin was unaffected by the presence of 1 mg/ml carboxymethylated (1----3)-beta-D-glucan . Spiked endotoxin was recovered well from beta-glucans by the turbidimetric kinetic method with LAL containing 1 mg/ml of carboxymethylated (1----3)-beta-D-glucan . Besides, this new LAL formulation was applied for an endotoxin-specific assay by the conventional gel-clot method or the chromogenic method . Gram-negative bacteria were specifically detected by the turbidimetric kinetic method with the LAL formulation . This LAL formulation may be used for an endotoxin-specific assay not only in pharmacology but also in clinical microbiology.

Lett Appl Microbiol, 1990 Nov, 11(5), 236 - 9
pIF21, a versatile donor of transposons Tn1, Tn5 and Tn7 for tagging and mobilizing cryptic and non-selectable plasmids; Feavers IM et al.; A plasmid, pIF21, has been constructed that is able to donate transposons Tn1, Tn5 and Tn7 . The transposons are located on a temperature-sensitive derivative of the incP1 plasmid pRP1, which is transferable to a wide range of Gram-negative genera.

Hosp Pract (Off Ed), 1990 Oct 15, 25(10), 121 - 3, 128-30
Management of gram-negative septic shock; Mostow SR; Gram-negative bacteremias in hospitalized immunocompromised patients can, of course, lead to sepsis and shock . How can such potentially disastrous infections be managed? Among the cornerstones of management that may curb mortality and morbidity are early recognition of infection, invasive monitoring and therapeutic techniques, and careful selection of antibiotics.

Appl Environ Microbiol, 1990 Oct, 56(10), 3204 - 8
Genes from Cellvibrio mixtus encoding beta-1,3 endoglucanase; Sakellaris H et al.; Two genes encoding beta-1,3 glucanase activity were cloned from the gram-negative soil bacterium Cellvibrio mixtus . The two clones, designated cwd (cell wall degradation) and lam (laminarin degradation), had distinct endonuclease restriction patterns and encoded enzymes with distinct substrate specificities . The 3.7-kilobase cwd insert encoded an enzyme which degraded yeast cell walls as well as the soluble beta-1,3 glucan laminarin and the insoluble beta-1,3 glucans zymosan and pachyman . The 1.8-kilobase lam insert encoded an enzyme which degraded laminarin only . Both enzymes degraded laminarin in an endohydrolytic manner to yield laminarobiose, laminarotriose, and laminarotetraose as major end products . Radiolabeled translation products of the cwd and lam transcripts were identified.

Avian Dis, 1990 Oct-Dec, 34(4), 1017 - 22
Plasma concentrations of enrofloxacin in African grey parrots treated with medicated water; Flammer K et al.; Plasma concentrations of enrofloxacin were measured four times during a 7-day treatment period in African grey parrots that were fed with enrofloxacin-medicated drinking water . Water medicated at doubling doses of 0.09, 0.19, 0.38, 0.75, 1.5, and 3.0 mg/ml achieved mean concentrations (+/- SEM) of 0.10 (+/- 0.05), 0.12 (+/- 0.05), 0.12 (+/- 0.03), 0.15 (+/- 0.05), 0.30 (+/- 0.11), and 0.20 (+/- 0.06) micrograms/ml, respectively . A portion of the administered enrofloxacin was metabolized to an equipotent metabolite, ciprofloxacin . Mean ciprofloxacin concentrations paralleled enrofloxacin concentrations but were lower, ranging from 0.04 to 0.27 micrograms/ml . Acceptance of medicated water was adequate at lower doses; however, at doses of 1.5 and 3.0 mg/ml, acceptance was unsatisfactory, and mean weight loss in these groups was significantly higher than the control group . Based on the concentrations achieved in these preliminary trials and the susceptibility patterns of gram-negative bacteria isolated from psittacine birds, drinking water medicated with enrofloxacin at 0.19-0.75 mg/ml might be effective for treating highly susceptible gram-negative bacterial infections in African grey parrots.

Eur Respir J Suppl, 1990 Oct, 11, 482s - 484s
Oxidant stress and adult respiratory distress syndrome; Brigham KL; Several experimental and theoretical lines of evidence implicate oxidant mechanisms in the diffuse lung injury which leads to the clinical syndrome called the adult respiratory distress syndrome (ARDS) . The fact that the injury is characterized by diffuse lung inflammation and that neutrophils can injure lung cells by producing reactive oxygen species provide all of the events necessary for extracellular oxidant stress as an important mechanism of injury . In experimental models and in the clinical syndrome, biochemical evidence of oxidant injury can be measured in the form of lipid peroxidation products . In some models, antioxidants, even antioxidant enzymes which do not access cell interiors, can protect the lungs from injury . There is also evidence that reactive oxygen species generated within lung cells may provide an additional oxidant mechanism of injury . Gram negative bacterial endotoxin can directly injure lung endothelial cells in culture . This injury is unaffected by superoxide dismutase or catalase (antioxidant enzymes which do not enter cells), but is prevented by several antioxidants which penetrate cells (including dimethyl sulphoxide, dimethyl thiourea and allopurinol) . The fact that allopurinol can inhibit direct lung cell injury by endotoxin suggests that xanthine oxidase may be a source of oxidant generation in lung endothelial cells . Current data suggest a two stage oxidant process of lung cell injury where there is both direct injury of the cell by intracellular generation of toxic oxidants and triggering of the inflammatory response . Activated inflammatory cells adherent to lung cells then enhance the injury by the generation and release of extracellular oxidants.

Eur J Clin Microbiol Infect Dis, 1990 Oct, 9(10), 725 - 31
Respiratory tract colonization and incidence of secondary infection during hospital treatment of community-acquired pneumonia; Ortqvist A et al.; In a prospective study of 245 patients with community-acquired pneumonia, the respiratory tract of 93 patients (38%) became colonized during hospitalization . Gram-negative rods and Candida spp . predominated, and in more than 75% of cases colonization occurred within 72 h after admission . Multivariate analysis showed that colonization was significantly associated with increasing age, presence of chronic disease, and with decreasing serum albumin and a respiratory rate of greater than 30/min on admission . Colonization was a negative prognostic factor, associated with a 14-fold higher mortality (10% vs . 0.7%), doubled length of hospital stay and a slower recovery . Seventeen patients developed a secondary infection . However, only two had lower respiratory tract infection, and one (0.4%) pneumonia verified by X-ray . The previously reported high risk of respiratory superinfection in this category of patient does not seem to apply today.

Eur J Clin Microbiol Infect Dis, 1990 Oct, 9(10), 711 - 6
Monoclonal anti-endotoxin antibodies for the treatment of gram-negative bacteremia and septic shock; Baumgartner JD; The role of anti-endotoxin antibodies in the management of gram-negative bacteremia and the experimental and clinical studies on the cross-protection afforded by core LPS antibodies are reviewed . These studies did not achieve clarification of the epitope(s) and effector mechanism(s) involved in protection . Recently, two anti-lipid A IgM monoclonal antibodies, designated E5 and HA-1A, have been investigated in patients with gram-negative bacterial infections and clinical manifestations of septicemia . E5 reduced the mortality of patients if they were not in shock, whether they were bacteremic or not . A confirmatory study has been initiated . In contrast to E5, HA-1A protected patients whether they were in shock or not, but only when they were bacteremic at randomization . Although these studies suggest beneficial effects, the type of patients who may benefit from this expensive therapy should be further defined . Further investigations are needed to clarify the mechanisms of protection of these antibodies.

J Pediatr Gastroenterol Nutr, 1990 Oct, 11(3), 317 - 23
Prevention of neonatal necrotizing enterocolitis; Carrion V et al.; Small premature infants are often hypochlorhydric, and frequently their stomachs are colonized by enteric, gram-negative bacteria . We tested a hypothesis that gastric pH affected the colonization of the stomach with enteric bacteria and that this colonization was causally related to the risk or severity of necrotizing enterocolitis . A prospective, double-blind study was conducted that compared a group of infants supplemented with 0.01-0.02 ml of 1 N HCl/ml of milk to a group with a similar supplement of water . Gastric pH, gastric enteric bacteria counts, and the incidence and severity of necrotizing enterocolitis were monitored . The median gastric pH of the HCl-supplemented group was lower (3.0) than controls (4.0) throughout the study (p less than 0.001) . The gastric enteric bacterial colonization rate and the quantitative bacterial counts were strongly correlated with gastric pH over 4 (p less than 0.001) . Somatic growth rates in infants in the HCl-supplemented group were equal to, or exceeded, those in the control group . There was 1 case of necrotizing enterocolitis among the 34 infants in the HCl-supplemented group and 8 cases among the 34 in the control group (p = 0.02) . It appears that acidifying the feedings of small premature infants to a pH low enough to inhibit bacterial proliferation in the stomach significantly lowers the risk of necrotizing enterocolitis.

J Child Neurol, 1990 Oct, 5(4), 318 - 20
Shunt-related brain abscess and ascending shunt infection; Gower DJ et al.; We report the fifth case of shunt-related brain abscess . Two prior cases have been associated with colonic perforation and infection with gram-negative enteric organisms . These cases strongly suggest that ascending shunt infection is possible despite bulk cerebrospinal fluid flow in the opposite direction and add to our understanding of shunt infections.

Scand J Immunol, 1990 Oct, 32(4), 313 - 9
Tumour necrosis factor alpha (TNF-alpha) and interleukin 6 in a zymosan-induced shock model; von Asmuth EJ et al.; TNF plays a central role in septic shock induced by endotoxin or Gram-negative bacteria . Zymosan can elicit a septic shock-like syndrome in rodents in the absence of endotoxin . TNF and IL-6 release in mice treated with zymosan was investigated . One hour after intraperitoneal zymosan injection, maximal TNF levels were measured in serum, followed by IL-6 peak levels 1 h later . Treatment with a monoclonal antibody against TNF lowered zymosan-induced mortality from 63 to 11.6%, while maximal IL-6 levels were lowered by about 40% . Mechanisms triggering zymosan-induced cytokine release in murine macrophages were analysed in vitro . Cytokine release was only slightly triggered by uncoated zymosan particles . Thirty-nine per cent of TNF release by macrophages appeared to be triggered by zymosan-bound activated complement . Maximal TNF release also required the presence of natural antibodies against zymosan and zymosan-activated serum . In contrast, maximal IL-6 release was reached upon stimulation with zymosan-activated serum only, while the presence of zymosan particles lowered this response . We conclude that TNF is a crucial mediator in zymosan-induced shock . TNF release can be induced by different immunological pathways, without the need for the direct presence of endotoxins . Although IL-6 release during septic shock is partly dependent on TNF, in vitro trigger mechanisms for IL-6 and TNF differ remarkably.

South Med J, 1990 Oct, 83(10), 1226 - 9
Disseminated strongyloidiasis in AIDS and non-AIDS immunocompromised hosts: diagnosis by sputum and bronchoalveolar lavage; Kramer MR et al.; In conclusion, disseminated strongyloidiasis is a fatal disease that commonly affects the lungs . The disease should be suspected in an immunocompromised host who came from an area endemic for S stercoralis even years before the onset of symptoms or in patients with unexplained gram-negative bacteremia or meningitis . Treatment should be started promptly and should be maintained for a long time.

Metabolism, 1990 Oct, 39(10), 1096 - 107
Insulin-mediated glucose uptake by individual tissues during sepsis; Lang CH et al.; Gram-negative hypermetabolic sepsis has been previously reported to produce whole body insulin resistance . The present study was performed to determine in vivo which tissues are responsible for the sepsis-induced decrease in insulin-mediated glucose uptake (IMGU), and whether that decrease was related to a change in regional blood flow . Vascular catheters were placed in rats and sepsis was induced by subcutaneous injections of Escherichia coli . Insulin action was assessed 20 hours after the first injection of bacteria by the combined use of the euglycemic hyperinsulinemic clamp and the tracer 2-deoxyglucose (dGlc) technique . Insulin was infused at various rates in separate groups of septic and nonseptic rats for 3 hours to produce steady-state insulin levels between 70 and 20,000 microU/mL . Rats were injected with {U-14C}-dGlc 140 minutes after the start of the euglycemic hyperinsulinemic clamp for the determination of the glucose metabolic rate (Rg) in selected tissues . The maximal response to insulin was decreased 30% to 40% in the gastrocnemius, and in the red and white quadriceps . The former two muscles also showed a decrease in insulin sensitivity . However, the insulin resistance seen in hindlimb muscles was not evident in all muscles of the body, since IMGU by abdominal muscle, diaphragm, and heart was not impaired by sepsis . The basal Rg by skin, spleen, ileum, and lung was increased by sepsis, and was higher than the insulin-stimulated increases in Rg by these tissues in nonseptic animals . Cardiac output was similar in septic and nonseptic rats and did not change during the infusion of insulin . Under basal conditions, sepsis appeared to redistribute blood flow away from the red quadriceps and skin, and increased flow to the liver (arterial), lung, and small intestine . When plasma insulin levels were elevated, hepatic arterial blood flow was increased, and flow to the red quadriceps and skin was decreased in nonseptic animals . Hyperinsulinemia did not produce any consistent change in regional blood flow in septic animals . The results of this study indicate that a decrease rate of IMGU in muscle is primarily responsible for the whole body insulin resistance seen during hypermetabolic sepsis, and that the impairment of insulin action in skeletal muscle is not dependent on fiber type or to changes in blood flow.

Thromb Res, 1990 Oct 1, 60(1), 9 - 18
Anticoagulant activity of a bacterial glycopeptide; Akoum A et al.; The anticoagulant properties of myxalin, a glycopeptide secreted by a Gram negative bacterium strain (Myxococcus xanthus) are studied and compared to those of heparin . This soluble material exhibits an anticoagulant activity which implies the inhibition of some serine proteases, thrombin and factor Xa . In the presence of normal and antithrombin III-depleted plasma, myxalin inhibits the amidolytic activity of thrombin on synthetic chromogenic substrate as a function of its concentration, but fails to increase thrombin inactivation significantly in the presence of purified AT III . However, crossed immunoelectrophoresis data suggests that its antithrombi effect is mainly mediated by binding to the enzyme, rather than to AT III and probably differs from the catalytic activity of heparin which requires the presence of AT III . The anticoagulant process occurs without degradation of fibrinogen and can be neutralized by protamine.

Mol Microbiol, 1990 Oct, 4(10), 1615 - 20
Molecular evolution of ubiquitous beta-lactamases towards extended-spectrum enzymes active against newer beta-lactam antibiotics; Collatz E et al.; Production of beta-lactamases, and of the plasmid-encoded TEM- and SHV-type enzymes in particular, is the most common mechanism of resistance against beta-lactam antibiotics in Gram-negative bacteria . The two ubiquitous types of enzyme have a large spectrum of activity and preferentially hydrolyse the penicillins as well as some first- and second-generation cephalosporins . Recently, point mutations in the corresponding genes have been observed, apparently selected for, in the clinical setting, by originally 'beta-lactamase-stable' third-generation cephalosporins or by monobactams, which fall into the substrate range of the mutant or 'extended-spectrum' beta-lactamases . The point mutations are clustered in three areas, each adjacent to one of the seven evolutionarily conserved boxes described by Joris et al . (1988) . The substituted amino acids at positions 102 (adjacent to the alpha-3 helix), 162 (adjacent to the alpha-7 helix) and 235, 236 and 237 (on the beta-3 strand) are located in close proximity to the active-site cavity and are thought to open up novel enzyme-substrate interactions, involving, in particular, the oxyimino moieties of the newer beta-lactam compounds.

J Appl Physiol, 1990 Oct, 69(4), 1502 - 8
Effect of synchronous increase in intrathoracic pressure on cardiac performance during acute endotoxemia; Guimond JG et al.; In the anesthetized closed-chest canine model of Gram-negative endotoxemia (n = 10), we tested the hypothesis that the effect of cardiac cycle-specific intrathoracic pressure pulses delivered by a heart rate-(HR) synchronized high-frequency jet ventilator (sync HFJV) on systolic ventricular performance is dependent on the level of preload . To control for HFJV frequency, hemodynamic responses were also measured at fixed frequency within 15% of HR (async HFJV) . Biventricular stroke volumes (SV) were measured by electromagnetic flow probes . Measurements were made before (baseline) and 30 min after infusion of 1 mg/kg Escherichia coli endotoxin (serotype 055:B5) and then after 2 mg/kg propranolol at both low (less than 10 mmHg) left ventricular filling pressure (LVFP) and high (greater than 10 mmHg) LVFP . Ventricular function curves, aortic pressure-flow (P-Q) relationships, and venous return (VR) curves were analyzed . We found that endotoxin did not alter VR curves but shifted the aortic P-Q curves to the left with pressure on the x-axis (P less than 0.05) . Volume loading increased SV (P less than 0.01) because of a rightward shift of the VR curve . No specific differences occurred with either sync or async HFJV during endotoxin, presumably because of preserved VR and shifted aortic P-Q . The lack of cardiac cycle-specific effects of ITP appears to be due to the selective endotoxin-induced changes in peripheral vasomotor tone that counterbalance any depressed myocardial contractility.

Science, 1990 Sep 21, 249(4975), 1429 - 31
Structure and function of lipopolysaccharide binding protein; Schumann RR et al.; The primary structure of lipopolysaccharide binding protein (LBP), a trace plasma protein that binds to the lipid A moiety of bacterial lipopolysaccharides (LPSs), was deduced by sequencing cloned complementary DNA . LBP shares sequence identity with another LPS binding protein found in granulocytes, bactericidal/permeability-increasing protein, and with cholesterol ester transport protein of the plasma . LBP may control the response to LPS under physiologic conditions by forming high-affinity complexes with LPS that bind to monocytes and macrophages, which then secrete tumor necrosis factor . The identification of this pathway for LPS-induced monocyte stimulation may aid in the development of treatments for diseases in which Gram-negative sepsis or endotoxemia are involved.

FEMS Microbiol Lett, 1990 Sep 15, 59(3), 299 - 303
Mapping of transcripts encoded by the plasmid in Chlamydia trachomatis; Sriprakash KS et al.; Mapping of the plasmid-encoded RNA of the intracellular parasite, Chlamydia trachomatis revealed that the upstream control elements are different from those of other Gram-negative bacteria . A tetranucleotide, AYAA was found near the -10 position, in 5 out of 8 upstream sequences described so far . The plasmid also has a developmentally regulated promoter . The chlamydial upstream elements do not function as promoters in E . coli and vice versa . An E . coli promoter-like sequence has been found to occur fortuitously upstream from the plasmid-encoded dnaB gene . Such sequences may be evolutionary relics.

Epilepsia, 1990 Sep-Oct, 31(5), 567 - 73
Factors predictive of seizures among intensive care unit patients with gram-negative infections; Guess HA et al.; From the medical records of 238 intensive care unit (ICU) patients who had infections with gram-negative pathogens commonly associated with serious illness, we developed a predictive score of clinical risk factors for seizures . To evaluate the predictive ability of this score, we applied it to a separate population of 645 seriously ill hospitalized patients with similar gram-negative infections who were in antibiotic clinical trials . The patients at highest risk were classified into one of the following three categories: (a) patients with major central nervous system (CNS) insults (CNS surgery, hemorrhage, infection, or other lesion within 1 month before hospital admission or any history of CNS neoplasia), (b) patients with a predisposing factor (renal impairment or a history of seizures) plus a precipitating factor (anoxic encephalopathy/coma or an acute hypotensive episode), and (c) patients with both renal impairment and a history of seizures . Receiver operating characteristic (ROC) curves were calculated in each of the two populations . The area under the ROC curve (AUC) represents the probability that the score would rank a randomly chosen patient who subsequently had a seizure as having had a greater prior level of seizure risk than a randomly chosen patient who did not experience a seizure . The AUC was 0.87 (SE = 0.05) for the original population used to develop the score and 0.81 (SE = 0.04) for the population used for the validation study . The clinical risk score, based on readily available information, provides a useful means to identify among seriously ill infectious disease service patients, those who are at highest risk for seizures . It also serves as a baseline for evaluating the non-drug-related risk factors for seizures in patients treated with antibiotics.

Am J Vet Res, 1990 Sep, 51(9), 1400 - 6
Immunologic factors related to survival and performance in neonatal swine; Tyler JW et al.; Logistic regression was used to develop models predicting preweaning survival in 334 neonatal swine . Measured risk factors included birth weight, litter size (live born), dam parity, serum IgG concentration, serum ELISA titers recognizing common gram-negative core antigens, and serum concentrations of the third component of complement . Larger birth weights were associated with increased probability of preweaning survival . The highest mortality was observed in litters with more than 12 pigs . Pigs with serum concentration of the third component of complement (C3) in the lowest stratum, less than 20% adult pooled C3 standard (APC3), had reduced mortality, compared with high (greater than 38% APC3) and middle (20 to 38% APC3) groups . Associations between all other variables, including total serum IgG concentration and preweaning survival were not significant . Few pigs had hypogammaglobulinemia, less than 3% of the study population had serum IgG concentrations less than 1 g/dl . Of all measured variables, only birth weight and dam parity were significant predictors of preweaning gain . Larger pigs and pigs born to third or greater parity dams had more preweaning gain than other pigs.

J Pharmacol Exp Ther, 1990 Sep, 254(3), 976 - 81
Protective effect of BN 50739, a new platelet-activating factor antagonist, in endotoxin-treated rabbits; Yue TL et al.; Platelet-activating factor (PAF) has been demonstrated in the circulation and organs of animals exposed to gram negative endotoxins, whereas PAF antagonists have been shown to exhibit some efficacy in modifying the course of endotoxemia . In this study we evaluated BN 50739, a novel specific PAF antagonist, for its capacity to block PAF or lipopolysaccharide endotoxin (LPS)-mediated effects in rabbits . Pretreatment with BN 50739 (3 and 10 mg/kg i.p.) inhibited PAF (500 pmol/kg i.v.)-induced thrombocytopenia, leukopenia and plasma thromboxane B2 elevation in a dose-dependent manner . The inhibitory effect lasted 3.5 to 4.5 hr . BN 50739 (10 mg/kg) prevented the early phase of LPS (50 micrograms/kg i.v.)-induced thrombocytopenia and thromboxane B2 elevation, and reduced the 24-hr mortality rate from 75 to 22% (P less than .05) . Post-treatment with BN 50739 increased the 10-hr survival rate from 33 to 87% (P less than .05); however, it had no effect on the 24-hr mortality . BN 50739 did not affect LPS-induced leukopenia or the elevation in plasma tumor necrosis factor . Our data support possible therapeutic efficacy of PAF antagonists in septic shock despite their inability to prevent the generation of tumor necrosis factor.

Antimicrob Agents Chemother, 1990 Sep, 34(9), 1806 - 8
Mode of action of GR69153, a novel catechol-substituted cephalosporin, and its interaction with the tonB-dependent iron transport system; Silley P et al.; GR69153 is a novel cephalosporin incorporating a catechol-substituted 7-aminothiazolyl-oxime . The antibiotic is actively transported into gram-negative cells via iron-regulated outer membrane proteins regulated by the tonB product . This transport enhances bactericidal activity most significantly at low concentrations, essentially removing the permeability barrier for antibiotic uptake.

Aust Vet J, 1990 Sep, 67(9), 323 - 30
Diseases of young captive crocodiles in Papua New Guinea; Ladds PW et al.; To identify causes of mortality in young captive crocodiles, detailed necropsy and laboratory examination was done on 54 (30 Crocodylus porosus, 22 C . novaeguineae, 2 of unrecorded species) . Although multiple infections often confounded interpretation it was concluded that the major infectious diseases, of approximately equal importance, were coccidiosis, bacterial septicaemia with Gram-negative organisms, and metazoan parasitism including ascariasis and pentastomiasis . A range of other lesions and agents was recognised, including keratitis, enteritis of unknown aetiology, non-suppurative encephalitis, traumatic peritonitis and trematodes located in renal tubules, gut and blood vessels . Some crocodiles in poor condition had only mild lesions associated with metazoan parasites and the cause of death or illness could not be clearly determined, although it was considered likely that adaptation failure was a contributing factor.

Semin Respir Infect, 1990 Sep, 5(3), 173 - 84
Gram-negative colonization of the respiratory tract: pathogenesis and clinical consequences; Niederman MS; The normal upper and lower respiratory tract are not colonized by enteric gram-negative bacteria (EGNB), but when serious illness develops, both sites may harbor these organisms . Colonization at either site is more likely when the severity of illness increases, and in critically ill patients, Pseudomonas species are the most common colonizing organisms, especially in the tracheobronchial tree . Many of the risk factors for colonization by EGNB have also been recognized as predisposing conditions for nosocomial pneumonia, and colonization may precede and predict this infection . Colonization should be viewed as a marker of a sick patient who had multiple host impairments; it is these defects that often allow colonization to progress to invasive infection . One pathogenetic mechanism that mediates colonization is an increase in epithelial cell bacterial adherence for EGNB . Many of the clinical conditions that favor colonization lead to an alteration in epithelial cell surface susceptibility to bacterial binding . Factors that influence adherence include cellular variables, bacterial surface characteristics and exoproducts, and the microenvironmental conditions at the airway surface . In order for adherence to mediate colonization, mucociliary clearance and other lower respiratory tract defenses must be abnormal . Based on an understanding of colonization pathogenesis, rational strategies for nosocomial pneumonia prophylaxis may emerge.

Med Hypotheses, 1990 Sep, 33(1), 49 - 56
An evolutionary perspective of endotoxin: a signal for a well-adapted defense system; Legrand EK; In the evolutionary view of endotoxin presented here, endotoxin is the primary signal animals use to detect gram negative (Gr-) bacteria . Since endotoxin, or lipopolysaccharide (LPS), is an integral part of the surface of all Gr- bacteria, it was excellent evolutionary 'choice' for the signal . The concept of an 'endotoxin response system' (ERS) is introduced . The ERS protects against Gr- bacteria by employing many of the body's defenses to both detect and react against LPS . The intensity of the response has evolved to maximize protection while minimizing the biological cost and self-damaging effects . The setting of the response, here termed the 'endostat', is programmed by natural selection and fine tuned by feedback mechanisms . Other potentially invasive organisms are detected by different signals, but the effector components of the defenses are similar . This evolutionary view of LPS offers a framework for the seemingly contradictory findings on endotoxin and suggests new avenues of productive research.

J Antimicrob Chemother, 1990 Sep, 26 Suppl A, 11 - 4
Tissue penetration of cefotaxime in normal pigs and pigs with haemorrhagic pancreatitis; Papenburg R et al.; This study was designed to evaluate the tissue penetration of cefotaxime in normal pigs and pigs with haemorrhagic pancreatitis . Serum, peritoneal fluid, bile, gallbladder wall and pancreatic tissue concentrations of cefotaxime in these groups of pigs exceeded the MIC90 for susceptible species of Gram-negative aerobic bacteria . Cefotaxime penetration into pancreatic tissue and peritoneal fluid was increased from 2% to 2.6% and 73% to 89%, respectively, in pigs with pancreatitis in comparison with normal pigs . These increases however, were not statistically significant.

Cesk Otolaryngol, 1990 Sep, 39(5), 249 - 53
{Personal experience with antibiotic prophylaxis in extensive otorhinolaryngologic procedures}; Taudy M et al.; The authors compare the effectiveness of three types of antibiotic prophylaxis (1 . cephazoline, 2 . combination ampicillin + oxacillin, 3 . clindamycin) in a group of 32 patients with resection of oropharyngeal carcinomas and in a group of 47 laryngectomies with cervical block resection . The criterium is the incidence of postoperative infections, which called for a change of antibiotic treatment . The authors evaluates favourably prophylaxis with cephazoline and clindamycin; the incidence of complications is within the range of 17-30% . In ampicillin + oxacillin therapy unsatisfactory results with a 46% incidence of inflammatory complications were recorded . A gram-negative flora causes 45% infectious complications; the author also draws attention to the danger of anaerobic infections . In a primarily contaminated oropharyngeal area there is an incidence of postoperative infections by 30% higher in all types of evaluated prophylaxis, as compared with the laryngocervical area.

J Trauma, 1990 Sep, 30(9), 1104 - 13; discussion 1113-5
Endotoxin (LPS) increases mesenteric vascular resistance (MVR) and bacterial translocation (BT); Navaratnam RL et al.; Endotoxemia is responsible for many of the pathophysiologic alterations that occur with Gram-negative sepsis . We utilized a chronic ovine model to determine the hemodynamic disturbances in the gastrointestinal tract during endotoxemia . Sheep with indwelling arterial, venous, and pulmonary arterial catheters were used . An ultrasonic flow probe was placed on the cephalic mesenteric artery . The animals were subjected to: 1) Ringer's lactate infusion (sham n = 6); or 2) 1.5 mcg/kg E . coli endotoxin (n = 6) over over a period of one half hour and were monitored for 48 hours . They were then sacrificed and specimens of mesenteric lymph node, liver, spleen, kidney, and lung obtained for bacteriologic cultures and histologic analysis . Sheep receiving endotoxin showed more than 50% reduction in the mesenteric blood flow . Mesenteric vascular resistance increased while non-mesenteric systemic vascular resistance decreased . The increase in the total systemic vascular resistance, noted during endotoxemia, was thus likely due to the increase in the mesenteric vascular resistance . At autopsy there were positive cultures for microorganism in the mesenteric lymph nodes in six out of six sheep with endotoxemia as compared to one out of six of control . Thus the vasoconstriction in the mesenteric areas may have resulted in bacterial translocation from the GI tract.

Infect Immun, 1990 Sep, 58(9), 2862 - 8
Inactivation of suppressor T cell activity by the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides; Baker PJ et al.; Antibody responses of mice immunized with type III pneumococcal polysaccharide were examined with and without treatment with nontoxic lipopolysaccharide from Rhodopseudomonas sphaeroides (Rs-LPS) . The results obtained were similar to those described previously for mice treated with monophosphoryl lipid A (MPL) except that lower amounts of Rs-LPS were needed . Both were without effect when given at the time of immunization with type III pneumococcal polysaccharide but elicited significant enhancement when given 2 to 3 days later . Such enhancement was T cell dependent and not due to polyclonal activation of immunoglobulin M synthesis by B cells . Treatment with either Rs-LPS or MPL abolished the expression but not induction of low-dose paralysis, a form of immunological unresponsiveness known to be mediated by suppressor T cells (Ts) . The in vitro treatment of cell suspensions containing Ts with extremely small amounts of Rs-LPS or MPI completely eliminated the capacity of such cells to transfer suppression to other mice . These findings indicate that the immunomodulatory effects of both MPL and Rs-LPS are mainly the result of eliminating the inhibitors effects of Ts; this permits the positive effects of amplifier T cells to be more fully expressed, thereby resulting in an increased antibody response . The significance of these and other findings to the use of Rs-LPS as a pharmacotherapeutic agent for gram-negative bacterial sepsis is discussed.

FEMS Microbiol Lett, 1990 Sep 1, 59(1-2), 149 - 55
Photosensitizing activity of water- and lipid-soluble phthalocyanines on Escherichia coli; Bertoloni G et al.; Escherichia coli, as most Gram-negative bacteria, is insensitive to the photosensitizing action of both lipid-soluble Zinc-phthalocyanine (Zn-Pc) and water-soluble Zinc-mono/disulfonated phthalocyanine (Zn-PcS) . Photosensitivity can be induced by alteration of the outer membrane, as obtained by either induction of competence or treatment with Tris-EDTA . Both phthalocyanines largely bind at the level of the cytoplasmic membrane; however, Zn-PcS shows a superior photosensitizing activity as compared with Zn-Pc . Biochemical analyses performed on irradiated cells suggest that the cytoplasmic membrane is an important target of the photoprocess, while DNA is not involved.

Jpn J Surg, 1990 Sep, 20(5), 559 - 66
A new method for the quantification of beta-glucan in plasma and its application in the diagnosis of postoperative infection; Yokota M et al.; In order to correctly diagnose and treat severe postoperative infections, it may be critical to detect and differentiate between endotoxin derived from Gram-negative bacteria and/or beta-glucan derived from fungi . In addition to the chromogenic assay, the turbidimetric kinetic assay has been performed for the quantification of endotoxin in plasma using Limulus amebocyte lysate as previously reported . However, it is also known that beta-glucan triggers the coagulation of Limulus amebocyte lysate . In the present study, the differentiation of beta-glucan from endotoxin and its clinical application were studied . Endotoxin was able to be inactivated in plasma using one-tenth dilution by 10 per cent ethanol or distilled water, followed by heating at 100 degrees C for 120 min, without affecting the activity of coexisting beta-glucan . The treated sample was then subjected to the turbidimetric kinetic assay using Toxinometer ET-201 . Using this method, as little as 30 pg/ml of beta-glucan in the plasma may be assayed separately, with the amount of circulating beta-glucan in the plasma of normal subjects being less than 50 pg/ml . On the other hand, in patients with a fungal infection, the amount of beta-glucan in their plasma was elevated significantly . Clinically, beta-glucanemia may often occur in severe postoperative infection even if fungi are not detected.

Plasmid, 1990 Sep, 24(2), 143 - 8
High-level expression vectors for Caulobacter crescentus incorporating the transcription/translation initiation regions of the paracrystalline surface-layer-protein gene; Bingle WH et al.; A number of plasmid vectors were constructed for high-level gene expression in the dimorphic gram-negative bacterium Caulobacter crescentus . These vectors incorporate the transcription and translation initiation regions of the C . crescentus CB15A rsaA gene, which codes for the abundantly synthesized protein comprising the bacterium's paracrystalline surface layer . The expression vectors are based on the broad-host-range IncQ plasmid RSF1010 (R300B) and incorporate the rsaA promoter and transcription start site . Some vectors also contain translation initiation information; these can result in the addition of as little as a single glycine residue to the protein encoded by the cloned segment . The vectors can be introduced into C . crescentus by electroporation at high frequency (ranging up to 10(6)-10(7) electroporants/micrograms DNA with surface-layer-deficient mutant C . crescentus CB2A) or conjugal transfer . They range in size from 10 to 12 kb, specify either chloramphenicol or kanamycin resistance, and possess the restriction sites EcoRI, BamHI, KpnI, and SstI for cloning genes downstream of the rsaA gene sequences . For a number of the vectors, the complete nucleotide sequence is known . A comparison was made between the expression of an endoglucanase gene from these plasmids in C . crescentus CB2A and CB15A and similar constructions under the control of lacZ alpha transcription and translation initiation signals carried on a pUC9 vector in an Escherichia coli host . The two expression systems compared favorably; cell lysates prepared from C . crescentus CB2A exhibited 40% of the endoglucanase activity of similarly prepared lysates from E . coli JM101 . Lysates prepared from C . crescentus CB15A exhibited only 8% of the endoglucanase activity of E . coli lysates.

Scanning Microsc, 1990 Sep, 4(3), 675 - 90; discussion 690-1
Microbial colonization in human periodontal disease: an illustrated tutorial on selected ultrastructural and ecologic considerations; Cobb CM et al.; The oral cavity is populated by a prodigious microbial flora that exhibits a unique successional colonization of enamel and subgingival root surfaces . A wide range of oral sites provide different ecologic conditions and are, therefore, populated by different commensal microbial combinations . The sequence of microbial colonization, regardless of location within the oral cavity, commences with the acquisition of salivary and/or crevicular fluid-derived pellicle . As the process of successional colonization of the gingival crevice area proceeds uninterrupted, achieving critical mass between 10 and 21 days, gingivitis becomes evident at a clinical level . However, at a histologic level, gingivitis may be evident within 2-3 days of plaque accumulation . The inflammatory response sufficiently alters the ecological conditions so as to allow proliferation of supragingival plaque into subgingival areas . The subgingival plaque becomes progressively more Gram-negative and anaerobic in nature as the periodontal pocket deepens, leading ultimately to a chronic, progressive deterioration of the periodontium--adult periodontitis . Both gingivitis and adult periodontitis are characterized by the successive colonization of cocci, short and long rods, filamentous microbes with "corn cob" and "bristle brush" formations, flagellated microbes, and spirochetes . Localized juvenile periodontitis (LJP), in contrast to the adult form of periodontitis, features a comparatively sparse microbial flora . The subgingival microbial colonization characteristically features cocci, short rods, coccobacilli, and spirochetes.

Immunology, 1990 Sep, 71(1), 120 - 6
Characterization of rat T-cell clones with bacterial specificity; Eastcott JW et al.; We have isolated 10 rat T-cell clones from the spleen or lymph nodes of seven different donors . These rats were immunized with 2-5 x 10(8) killed Actinobacillus actinomycetemcomitans (Aa) bacteria, injected either subcutaneously (s.c.) in complete Freund's adjuvant or intraperitoneally (i.p.) in saline . Clones studied to date have demonstrated a T-helper (Th) phenotype W3/13+, W3/25+, OX8- and OX22- . Clones were not stimulated in vitro by purified Aa-lipopolysaccharide (LPS) or heterologous Gram-negative bacteria, but proliferated when stimulated by bacteria representative of each of the three serological groups of Actinobacillus, indicating specificity for an Actinobacillus-common antigen other than LPS . One clone (A4) proliferated vigorously when stimulated with concanavalin A (Con A) in vitro, produced interleukin-2 (IL-2) and was provisionally classified as a Th1 type . This appears to be one of the few Th1-type rat clones reported . All other clones tested did not produce IL-2, exhibited B-cell help to some extent, did not induce delayed-type hypersensitivity (DTH) when injected into the footpads of naive rats along with the specific antigen, and were classified as Th2 type . Adoptive transfer of 10(6) cells of one Th2-type Aa-specific clone into syngeneic recipients resulted in a specific splenocyte in vitro response to Aa 12-14 weeks after cell transfer, indicating survival of cloned cells in recipient animals . The use of such clones in studies of experimental periodontal disease is discussed.

J Bacteriol, 1990 Sep, 172(9), 5352 - 9
Mechanism of O-antigen distribution in lipopolysaccharide; Goldman RC et al.; O-antigen units are nonuniformly distributed among lipid A-core molecules in lipopolysaccharide (LPS) from gram-negative bacteria, as revealed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; the actual distribution patterns are complex, multimodal, and strain specific . Although the basic biochemical steps involved in synthesis and polymerization of O-antigen monomers and their subsequent attachment to lipid A-core are known, the mechanism by which specific multimodal distribution patterns are attained in mature LPS has not been previously considered theoretically or experimentally . We have developed probability equations which completely describe O-antigen distribution among lipid A-core molecules in terms of the probability of finding a nascent polymer (O antigen linked to carrier lipid) of length k (Tk) and the probability that a nascent polymer of length k will be extended to k + 1 by polymerase (pk) or transferred to lipid A-core by ligase (qk) . These equations were used to show that multimodal distribution patterns in mature LPS cannot be produced if all pk are equal to p and all qk are equal to q, conditions which indicate a lack of selectivity of polymerase and ligase, respectively, for nascent O-antigen chain lengths . A completely stochastic model (pk = p, qk = q) of O-antigen polymerization and transfer to lipid A-core was also inconsistent with observed effects of mutations which resulted in partial inhibition of O-antigen monomer synthesis, lipid A-core synthesis, or ligase activity . The simplest explanation compatible with experimental observations is that polymerase or ligase, or perhaps both, have specificity for certain O-antigen chain lengths during biosynthesis of LPS . Our mathematical model indicates selectively probably was associated with the polymerase reaction . Although one may argue for a multimodal distribution pattern based on a kinetic mechanism i.e., varying reaction parameters in space or in time during cell growth, such a model requires complex sensory and regulatory mechanisms to explain the mutant data and mechanisms for sequestering specific components of LPS biosynthesis to explain the distribution pattern in normal cells . We favor the simple alternative of enzyme specificity and present generalized equations which should be useful in analysis of other analogous biochemical systems.

Orv Hetil, 1990 Aug 19, 131(33), 1803 - 6, 1809
{The value of the d-xylose loading test in the diagnosis of malabsorption syndromes}; Horvath K et al.; The test of d-xylose concentration in blood has been used for approximately two decades for the examination of the absorption . The authors compared in 261 cases the total d-xylose blood level with the histological picture of the small intestine . Good correlation was observed between the 2 examinations . The d-xylose loading was found to select with favorable efficacy the new cases of celiac disease, of 63 fresh diagnosed subtotal and total villus atrophy cases the blood level of 61 was under the 1,64 mmol/l limit . At the 3rd stage of partial villus atrophy the blood level was pathological in 17 new patients . The sensitivity of the examination was 92.2% in selection of the new cases . Significant differences were found between the new cases and patients with excess gliadin (0.929 +/- 0.44 mmol/l and 1383 +/- 0.052 mmol/l) with identical rate of duodenal tissue impairments . On this basis the significant decrease of d-xylose level (0.5-1 mmol/l) must be regarded as the sign of relapse in patients with excess gliadin . Giardia lamblia and slight villus impairment was found in the biopsy material of further 28 children . The d-xylose level was pathological in 14 of them . D-xylose absorption was pathological before treatment in each of the 13 patients with contaminated (Gram-negative aerobic bacteria) small intestinal syndrome . D-xylose test is a useful method in the diagnostics of conditions associated with malabsorption and completed with other techniques it provides means for the separation of conditions associated with the diffuse impairment of the small intestine.

Thromb Haemost, 1990 Aug 13, 64(1), 3 - 6
Types 1 and 2 plasminogen activator inhibitor and tumor necrosis factor alpha in patients with sepsis; Paramo JA et al.; We have determined the plasma concentrations of types 1 and 2 of plasminogen activator inhibitor (PAI-1 and PAI-2), tumor necrosis factor (TNF-alpha) and endotoxin in 47 patients with bacterial infection (22 patients presented with positive blood cultures) . Results were compared with those observed in 30 healthy subjects . There was a significant increase in PAI-1 and TNF-alpha in patients as compared to controls (p less than 0.0001), whereas no differences for PAI-2 were observed . PAI-1 and TNF-alpha were significantly higher in 18 patients with gram-negative bacteremia as compared to all other patients (p less than 0.0001) . However, no correlation between the analyzed parameters and either endotoxin or clinical outcome was observed . We conclude that there is an increase of PAI-1 and TNF-alpha in patients with sepsis, which is not related to the endotoxin concentration . Our results suggest that PAI-1, but not PAI-2, is the main plasminogen activator inhibitor in human sepsis.

Orv Hetil, 1990 Aug 5, 131(31), 1687 - 90
{Contaminated small bowel syndrome in infants caused by gram-negative bacteria and yeasts}; Bodanszky H et al.; The upper small intestine is usually "sterile" in a healthy individuals, but due to some reasons the number of microorganisms may reach or increase above 10(4)/ml, leading to the contamination of the small intestine, which may cause severe malabsorption . The authors have diagnosed this syndrome in 50 children, aged between 1 month and 3 years, using breath hydrogen test and duodenal juice culture . Most of these children had growth retardation . According to their experience the authors found that the oral antibiotic is the effective treatment of this syndrome.

J Clin Periodontol, 1990 Aug, 17(7 Pt 1), 435 - 45
A case report of chronic neutropenia: clinical and ultrastructural findings; Vaughan AG et al.; This case report of severe periodontitis concerns a young male patient with chronic idiopathic neutropenia seen between 1981 and 1983 by the School of Dental Medicine of Geneva and from 1984 to 1988 by the Eastman Dental Hospital of London . The patient was maintained by intermittent systemic antibiotics, subgingival chlorhexidine irrigation, conventional debridement, brushing, and wire-mesh and composite splinting of loose teeth . After leaving school, at the patient's express wish, the extreme downhill pattern of the periodontitis resulted in removal of affected teeth and overdenture construction . The extracted teeth and associated soft tissues were examined for relevant plaque and host response features . The intact morphotypes associated with the advancing front of the lesion were invariably Gram-negative or positive coccoid cells, or less commonly short rods, as in all documented forms of periodotitis . Connective tissue destruction was associated with a leucocyte accumulation comprising mainly polymorphonuclear neutrophils (PMN) and plasma cells . Both were observed degenerated more deeply than in routine adult periodontitis, including PMN lysosome loss and lymphocyte maturation within peripheral blood vessels . Only in one instance, one part of the superficial connective tissue of one block contained bacteria . It was concluded that the features of plaque and the lesion suggest a typical first line of defence response as in other forms of periodontitis . From the consideration of the 10 years clinical history of the patient, it is clear that non-surgical management is possible even in extreme cases, without any compromise of the patient's oral or systemic health, and in accord with the patient's wishes.

Minerva Stomatol, 1990 Aug, 39(8), 697 - 701
{Modifications in the clinical and microbiological parameters of the periodontal tissues after the removal of overhanging class-II amalgam fillings}; Paolantonio M et al.; A short-term longitudinal study was carried out to assess how microbiological and clinical characteristics, measured surrounding periodontal sites with amalgam class II fillings intentionally made to overhang, vary following their replacement with a correct form of filling . The results of the study showed a significant reduction of the total bacterial count and the percentages of Gram-negative and anaerobic organisms spreading from overhanging fillings to non-overhanging fillings . The paper concludes that, as has been already demonstrated in the case of onlays, there are both qualitative and quantitative variations in the subgingival plaque in the presence of overhanging fillings which can lead to periodontal damage.

Mol Microbiol, 1990 Aug, 4(8), 1407 - 11
A rapid method for reconstitution of bacterial membrane proteins; Varadhachary A et al.; We have devised a simple method for the reconstitution of bacterial membrane proteins directly from small (1-20 ml) volumes of cell culture, thus eliminating the preparation of membrane vesicles . Cells are subjected to simultaneous lysozyme digestion and osmotic lysis, and after brief centrifugation ghosts are solubilized in 1.2% octyl-beta-D-glucopyranoside (octylglucoside) in the presence of added carrier lipid and an osmolyte . Aliquots of the clarified supernatant are suitable for reconstitution, as documented by using extracts from three different Gram-negative cells to recover both inorganic phosphate (Pi)-linked antiport and oxalate:formate exchange activities in proteoliposomes . These proteoliposomes are physically stable, non-leaky and can sustain a membrane potential and, because functional porins do not reconstitute, the artificial system has transport characteristics similar to those found when proteoliposomes are obtained using standard methods . This method should become an important tool for the screening and characterization of large numbers of strains, both wild-type and mutant.

J Paediatr Child Health, 1990 Aug, 26(4), 212 - 6
Neonatal gram negative meningitis: a 10-year review, with reference to outcome and relapse of infection; Anderson SG et al.; Twenty-four infants treated for neonatal Gram negative bacillary meningitis over a 10-year period were reviewed to determine the mortality and incidence of complications including relapse . Nine (37.5%) infants died; two survivors had major and 13 minimal or no handicap . Five (21%) infants had a relapse of meningitis after the initial course of treatment; two of these infants had been treated with cefotaxime . The outcome did not correlate with age, sex, gestation, cerebrospinal fluid (CSF) parameters or peripheral neutrophil counts . A poor outcome was associated with thrombocytopenia, persistence of viable organisms in the CSF for more than 24 h and with seizures, particularly in infants aged 7 days or less . There were no clinical or laboratory parameters predictive of subsequent relapse and there was no apparent relationship with choice or dose of antibiotic used or duration of treatment.

Tijdschr Gerontol Geriatr, 1990 Aug, 21(4), 179 - 81
{Pneumonia in the elderly}; van der Meer JW; In the aged, pneumonia is associated with considerable morbidity and mortality . As a consequence of ageing, decreased mobility, underlying illnesses and medication, especially the host defense mechanisms in the respiratory tract may become deficient . The kind of micro-organism that causes the infection depends on whether the patient lives at home or whether he is institutionalised (nursing home, skilled nursing facility, hospital) . Pneumonia in patients at home is mainly caused by pneumococci, whereas in institutionalised patients also other micro-organisms, especially Gram-negative bacteria are the cause . The diagnosis is often difficult due to the lack of symptoms and signs in the aged patient . An important sign is tachypnea . For the choice of anti-microbial therapy the question whether the patient acquired the infection at home or in an institution is crucial, as is the question, whether the patient has recently used anti-microbial drugs . Finally, therapy differs in patients that produce sputum and in those who do not.

Am J Physiol, 1990 Aug, 259(2 Pt 2), H504 - 11
Left ventricular dysfunction in early E . coli endotoxemia: effects of naloxone; Parker JL et al.; Although the opiate receptor antagonist naloxone (NAL) has been reported to improve in vivo systolic performance of the heart in different circulatory shock syndromes, the influence of this drug on intrinsic cardiac mechanical function during hypodynamic circulatory states is unknown . The present study was designed to determine the effects of in vivo NAL on contraction-relaxation properties of isovolumic left ventricular (LV) preparations isolated from guinea pigs 4 h after induction of gram-negative endotoxemia . Animals were given a 1 mg/kg ip injection of Escherichia coli endotoxin and immediately treated intravenously with either NAL (4 mg/kg iv bolus plus 4 mg.kg-1.h-1 infusion) or an equivalent volume of saline . Endotoxin produced significant reduction of LV contractile function in coronary-perfused hearts, a response unaffected by NAL therapy . For example, LV systolic pressure at approximately 10 mmHg end-diastolic pressure averaged 78 +/- 3 and 82 +/- 6 mmHg in hearts from saline and NAL control animals, respectively, but only 41 +/- 2 and 40 +/- 2 mmHg in endotoxin and endotoxin plus NAL groups, respectively . LV end-diastolic pressure-volume relationships in endotoxin hearts were shifted upward and to the left of controls in the direction of decreased diastolic compliance (P less than 0.05) . Importantly, in vivo NAL prevented the endotoxin-induced decrease in LV compliance of the isolated heart preparations (P less than 0.05) . Thus intrinsic cardiac complications of early (4 h) nonhypotensive endotoxemia included decreased diastolic compliance as well as diminished contractility of the left ventricle . Only the diastolic compliance changes were NAL responsive and therefore may involve endogenous opioid systems in their pathophysiological expression.

J Infect Dis, 1990 Aug, 162(2), 454 - 9
Monoclonal antibody to endotoxin core protects mice from Escherichia coli sepsis by a mechanism independent of tumor necrosis factor and interleukin-6; Silva AT et al.; To study the role of cytokines as mediators of endotoxin-induced shock, the serum levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were compared in mice receiving either a monoclonal antibody to endotoxin core (clone 20), an irrelevant monoclonal antibody (A1), or culture media (DMEM/FCS) alone before lethal challenge with live Escherichia coli O111:B4 . Clone 20 given 1.5 h before the bacterial challenge protected mice from death (mortality at 48 h 3% vs . 87%, P less than .001) . The pattern of IL-6 release was indistinguishable in clone 20 recipients and controls: The area under the curve (AUC) for 5 h was 1.22 +/- 0.07 x 10(6), 1.03 +/- 0.17 x 10(6), and 1.22 +/- 0.07 x 10(6) units/ml for clone 20, A1, and DMEM/FCS, respectively . Similarly, the timing and extent of TNF release in the serum was virtually identical in clone 20 recipients that survived and control animals that died . AUC for 5 h was 30.8 +/- 4.0 x 10(3), 28.1 +/- 1.1 x 10(3), and 30.4 +/- 4.7 x 10(3) ng/ml in clone 20, A1, and DMEM/FCS recipients, respectively . Thus, TNF and IL-6 appear insufficient to cause death in this model of experimental gram-negative shock.

J Hosp Infect, 1990 Aug, 16(2), 167 - 72
Quantitative determination of endotoxins on surgical gloves; Peiro SA et al.; The amount of endotoxin on surgical gloves was investigated by the limulus chromogenic substrate method . Heavy endotoxin contamination was observed on the outside of certain surgical gloves sold in Sweden . Given an endotoxin absorption of 10% to the patients, one of the types of gloves studied would cause fever, chills, headache and muscle pain . The amount of endotoxin on the gloves could be minimized by rinsing in endotoxin-free water . We conclude that the manufacturing process of latex gloves should be checked microbiologically for Gram-negative bacteria before sterilization . Alternatively, the amount of endotoxin should be checked on the product by the limulus ameobocyte lysate test before release.

Vet Microbiol, 1990 Aug, 24(2), 199 - 204
A spiral microorganism in the stomach of pigs; Queiroz DM et al.; Light and electron microscopic and microbiologic evaluations were performed on mucosa of stomachs from 120 healthy slaughtered pigs . Helicobacter pylori was not found, but a tightly spiralled bacterium, not previously described, was seen in histological sections and/or in carbol fuchsin stained smears in 13 (10.8%) stomachs . In paraffin sections stained with carbol fuchsin, the bacteria were seen in the mucus of the lumen of the antral pits and in the mucosa surface within and beneath the mucus . In this sections of Polilyte embedded tissue the bacteria had three to eight spiral turns per cell (mean = five), flattened ends, a Gram-negative cell-wall structure and a sheathed flagella . The urease test was positive in gastric mucosa of 13 bacteria-positive pigs (10.8%) . The microorganism was not cultured and did not cross-react with polyclonal antibodies raised in rabbits against H . pylori . Superficial chronic gastritis and "borderline" gastritis were observed in antral mucosa of 10 (76.9%) and of two (15.4%) spiral bacteria-positive pigs, respectively.

Arch Dis Child, 1990 Jul, 65(7), 771 - 3
Serum immunoglobulins to endotoxin core glycolipid: acute leukaemia and other cancers; Jackson SK et al.; Circulating antibody to endotoxin core glycolipid and total serum immunoglobulin concentrations were measured in 86 children with cancer (54 with acute lymphoblastic leukaemia, four with acute myeloid leukaemia, and 28 with various solid tumours) . Measurements were made before treatment in the group with acute lymphoblastic leukaemia as well as when patients were both on and off chemotherapy . In the other two groups measurements were made when patients were both on and off treatment . Significant reductions in endotoxin antibody and serum immunoglobulin concentrations were found only in patients with acute lymphoblastic leukaemia . In addition, there was a significant correlation between febrile episodes and the concentration of antibody to core glycolipid in the children with acute lymphoblastic leukaemia . These findings suggest that the use of prophylactic high titre endotoxin antibody may be of benefit to children with life threatening Gram negative infections who are receiving cytotoxic chemotherapy.

Arch Dis Child, 1990 Jul, 65(7), 768 - 70
Serum immunoglobulins to endotoxin core glycolipid: establishment of normal concentrations; Jackson SK et al.; Serum antibody to lipopolysaccharide core glycolipid was measured in normal children and in full term and premature (less than or equal to 1500 g) infants . Antilipopolysaccharide core glycolipid antibody was present in term infants and normal children, and reached adult titres by 15 years of age . The specific anti core glycolipid antibody was predominately of the IgG class . Preterm infants (less than 32 weeks' gestation) had significantly lower titres of antilipopolysaccharide core glycolipid than more mature preterm or term infants . The results suggest that administration of anticore glycolipid immunoglobulin may be beneficial in the treatment or prevention of Gram negative septicaemia in preterm and very young infants.

Orv Hetil, 1990 Jul 1, 131(26), 1411 - 4
{Information data on the incidence of nosocomial infections in Hungary}; Pall G et al.; Authors registered the occurrence of nosocomial infections in altogether 1000, randomly selected case records at the surgical, gynecological, urological and intensive care wards of four county hospitals plus one large hospital in the capital in 1988 . They found the proof of a total of 117 nosocomial infections occurring in 100 case records . The three most common infections in diminishing order were: urogenital-, wound- and respiratory infections . Twenty three infected patients developed sepsis, with a fatal outcome in every second among them . A nosocomial infection extended the period of hospital treatment in average by a week . In more than half of the cases microbiological examination for detecting the causative agent failed . Four fifth of the isolated bacteria were Gram-negative . Presented data of informatory nature suggest more decades arrearagement compared to the highly-developed countries.

Heart Lung, 1990 Jul, 19(4), 371 - 2
Poststernotomy mediastinitis; Rosenbaum GS et al.; The clinician should suspect mediastinitis in patients after sternotomy who have unexplained fever or leukocytosis, sternal wound tenderness, or atypical chest or neck discomfort 2 to 3 weeks following surgery . Mediastinitis should be considered if any of these features are present . The diagnosis should be aggressively pursued by mediastinal aspiration via the suprasternal notch . Early empiric treatment with an antibiotic(s) with antistaphylococcal and gram-negative coverage is critical to survival.

Am J Hosp Pharm, 1990 Jul, 47(7), 1551 - 4
Procedural compliance and clinical outcome associated with therapeutic interchange of extended-spectrum penicillins; Martin LA et al.; The degree of procedural compliance and the clinical outcome associated with a therapeutic interchange of extended-spectrum penicillins were assessed . Pharmacists conducted a concurrent chart review on all patients receiving mezlocillin as a therapeutic alternative for piperacillin or ticarcillin over a five-month period . The pharmacists assessed whether (1) the pharmacy appropriately dispensed mezlocillin when orders were written for piperacillin or ticarcillin, (2) physicians and nurses were properly notified of the therapeutic interchange, and (3) the bacterial isolates were susceptible to mezlocillin . Pharmacists and physicians evaluated clinical outcomes of all patients receiving mezlocillin through a retrospective chart review and classified the responses as "success," "failure," or "indeterminate." Fifty-one orders for piperacillin were written during the study period, and mezlocillin was selected as a therapeutic alternative in all cases . No orders for ticarcillin were written . Proper notification was made to nurses and physicians in 98% and 65% of cases, respectively . No mezlocillin-resistant gram-negative bacteria were found . Eighty-three courses of therapy were reviewed for clinical outcome; 68 were classified as successes, 0 were failures, and 15 were indeterminate . The cost savings after nine months of therapeutic interchange of mezlocillin for piperacillin was $6600 . This study indicates that the pharmacy made a proper therapeutic interchange of mezlocillin for piperacillin and followed the correct procedure for notification of the nursing staff . However, more effort is needed to ensure communication with the prescribing physicians.

Dig Dis Sci, 1990 Jul, 35(7), 909 - 11
Capnocytophaga infection involving a portal-systemic vascular shunt; Mello KA et al.; Capnocytophaga sp., a microaerophilic gram-negative isolate of the human oral cavity, has previously been reported to cause sinusitis, empyema, wound infections, conjunctivitis, subphrenic abscess, osteomyelitis, bacteremia, cervical abscess, and endocarditis . We report the unusual case of infection with this organism at the anastamotic site of a splenorenal portosystemic vascular shunt . In this case, the pathogenesis is presumed to be bacteremia related to mucosal trauma from endoscopic injection sclerotherapy or bacteremia secondary to dental infection . The characteristics and antibiotic sensitivities of Capnocytophaga are reviewed.

Trop Gastroenterol, 1990 Jul-Sep, 11(3), 152 - 7
Spirochetal dysentery: a case report and review of literature; Singh S et al.; Spiral shaped bacteria have frequently been demonstrated from human faeces . Their role in causation of disease is, however, controversial; as they have been found to colonise the lower gastrointestinal tracts of both symptomatic and asymptomatic individuals . Here we report a case in which spiral shaped motile, gram negative and nonflagellated bacteria, probably belonging to the genus Borrelia, were demonstrated and associated with acute bloody diarrhea in a cardiac patient . The condition could successfully be treated with short course of Metronidazole . The relevant and up to date literature on this problem is also reviewed.

Acta Chir Belg, 1990 Jul-Aug, 90(4), 204 - 6
{Fournier's gangrene}; Leenen LP et al.; Two patients with a necrotizing soft tissue infection of the scrotum and perineum are described . The etiology was found to be a gram negative synergistic gangrene . Patients were managed with extensive necrotectomy with a planned second look operation and supportive antibiotics (aminoglycosides, amoxicillin, metronidazole) . Despite this aggressive approach one of the patients died of ongoing necrosis . The therapeutic management for necrotizing soft tissue infection comprises early surgical intervention with supportive antibiotic treatment . Nevertheless the disease is associated with a high mortality rate.

East Afr Med J, 1990 Jul, 67(7), 473 - 7
Prevalence of gonorrhoea, syphilis and trichomoniasis in prostitutes in Burkina Faso; Damiba AE et al.; Prevalence of syphilis, gonorrhoea and trichomoniasis among 127 prostitutes in Ougadougou, Burkina Faso, was investigated . 22% were positive of syphilis, 20% for intracellular gram negative diplococci, and 17% for Trichomonas vaginalis infection . Demographic data revealed that the prostitutes were a young group, with 69% between 15 and 25 years old . 14% of the women were from Burkina Faso; the majority (73%) were of Ghanaian origin . Our data highlight alarming rates of STDs in prostitutes working in Ouagadougou . Education campaigns which consider sociodemographic and cultural characteristics of the prostitutes should be established to reduce these rates . Upgrading of diagnostic capabilities and focal mass drug administration among prostitutes should also be considered . Data for this study were collected at Yalgado Ouedraogo Hospital, Ouagudougou, Burkina Faso, and analyzed at Columbia University School of Public Health and at Montefiore Medical Center/Albert Einstein College of Medicine, New York, USAPIP: The incidence of syphilis, gonorrhea and trichomoniasis was tested in 127 prostitutes in Ougadougou, Burkina Faso, by gram stain of intracellular gonococci, Wasserman test, and wet mount in January 1984 . The prostitutes were selected from police lists . Only 13.9% were Burkinabe; 72.9% were from Ghana; the rest were from Nigeria, Niger, Senegal, Togo and Gambia . 20% of the cervical smears were positive for gonococci, 17.2% were positive for trichomonas, and 22% were positive for syphilis . 45% of the prostitutes were low status, 38% were middle status, and 17% were high status . The results were considered unrealistically low for gonorrhea because of low sensitivity of the test, but probably accurate for syphilis . Registration, health monitoring and treatment of prostitutes would be advisable, but mass drug administration would be more cost effective to decrease prevalence of STDs (sexually transmitted diseases) .

Cytokine, 1990 Jul, 2(4), 253 - 8
Dissociation between the interleukin 1-inducing capacity and Limulus reactivity of lipopolysaccharides from gram-negative bacteria; Laude-Sharp M et al.; In this study we compared the interleukin 1 (IL 1)-inducing capacity and the reactivity in the Limulus amoebocyte assay (LAL) of purified lipopolysaccharides (LPSs) from various bacterial strains . LPSs differed greatly in their capacities (on a weight basis) to induce IL 1 release from serum-free cultured human monocytes . LPS species that induced high levels of IL 1 release from human monocytes exhibited a high thiobarbiturate-reactive 2-keto-3-deoxy-octonic acid (KDO) content . No relationship was found between the IL 1-inducing activity and the LAL reactivity of purified LPSs . Filtration experiments in which membranes of decreasing size-exclusion limits were used demonstrated that molecular species of LPS with an apparent Mr below 3,000 may induce IL 1, whereas only species with an apparent Mr above 8,000 are recognized in the LAL assay . The latter observation suggests that the reaction with LAL requires an aggregated form of LPS . These results indicate that biologically active LPS species can cross dialysis membranes in vivo although no LAL reactive material is detected in the blood compartment . The Limulus assay is an insufficient criterion for the absence of LPS in biological fluids.

Eur J Biochem, 1990 Jun 20, 190(2), 359 - 63
Architecture of bacterial lipid A in solution . A neutron small-angle scattering study; Labischinski H et al.; The phase structure of isolated bacterial lipid A, the lipid anchor of the lipopolysaccharides of the outer membrane of Gram-negative bacteria, has been investigated by neutron small-angle scattering . The shape of the scattering curves obtained at different H2O/2H2O ratios revealed a lamellar organisation of the lipid A at neutral pH both above and below its main phase temperature (approximately 40-45 degrees C) . Analysis of the scattering curves and interpretation of the corresponding thickness distance distribution functions of the lamellar aggregates led to a model in which the lipid A molecules form a bilayer of about 5 nm in thickness . This value for the thickness of the bilayer, as well as the neutron-scattering density profile across the bilayer, can be explained by a molecular model which shows interdigitation of the fatty acid chains of the lipid A.

Ugeskr Laeger, 1990 Jun 18, 152(25), 1824 - 7
{Microbial contamination of tube feeding solutions}; Jorgensen L et al.; Forty patients receiving respirator treatment were subdivided at random to receive tube-feeding with either a "home-made" powder product (group 1) or a ready-made sterile standard tube-feeding product: Salvimulsin MCT (group 2) . Tube-feeding was administered as a continuous drip infusion and the patients were followed throughout three days, with particular attention to the development of diarrhoea . A series of cultures were taken from the tube-feeding diet, at the beginning and end of an infusion . The volumes were similar in both of the groups and averaged 860 ml on the first day and approximately 1,300 on the second and third days . Significantly greater bacterial contamination was found in the "home-made" tube-feeding diet, particularly with growth of Gram-negative rods . Seven patients (35%) in group 1 and two patients (11.1%) in group 2 developed diarrhoea . This difference is not statistically significant . No correlation was found between hypoalbuminaemia and the development of diarrhoea . It is concluded that powder mixtures and dilution of tube-feeding diets should be avoided on account of the risk of contamination and, similarly, tube-feeding should not be administered for more than 6-8 hours.

Eur J Pediatr, 1990 Jun, 149(9), 645 - 7
Serum tumour necrosis factor in newborns at risk for infections; Girardin EP et al.; Tumour necrosis factor-alpha (TNF-alpha) is an important mediator in the pathogenesis of Gram-negative shock . In order to assess the role of TNF-alpha as a marker of the severity of infections in the neonates, serum TNF-alpha concentrations were determined at the time of septic work-up in 69 newborns (gestational age: 28-40 weeks) . Nine patients had systemic infection (group A), four of them with signs of circulatory failure . Eleven patients had positive cultures of gastric aspiration or placental smears (group B) and 49 patients had completely negative septic work-up . Patients of group A had significantly more elevated serum TNF-alpha levels than patients of group B and C . Within group A, patients with circulatory failure had mean serum TNF-alpha concentration of 2165 +/- 817 pg/ml versus 27 +/- 8 pg/ml in newborns without shock . Serum TNF-alpha concentrations of more than 15 pg/ml detected systemic infections in eight out of nine patients . The specificity was 98% (1 elevated TNF-alpha concentration out of 60 non infected patients) . These data indicate that premature neonates and term newborns are able to produce TNF-alpha when they are infected . Highly elevated TNF-alpha concentrations are found in severe systemic infections causing cardiovascular impairment.

Crit Care Med, 1990 Jun, 18(6), 607 - 10
Influence of amikacin as the primary aminoglycoside on bacterial isolates in the intensive care unit; Hammond JM et al.; Amikacin was introduced as the primary aminoglycoside in our hospital to prevent the further development of multiply resistant Gram-negative organisms . This study compares clinical and microbiological data before and after institution of this policy to evaluate the influence on clinical outcome in patients as well as changing resistance patterns in the respiratory ICU . Patient populations were similar in terms of severity of illness (Acute Physiology and Chronic Health Evaluation II scores), age, ventilation, invasive procedures, and the incidence of various diseases . We found that the rate of amikacin resistance increased from 8.5% to 39.6% with an increase in resistance to tobramycin (19.3% to 33.3%) and netilmicin (23.9% to 47.9%) over the same period despite minimal usage of these drugs . The clinical outcome was similar in the periods contrasted . Our findings suggest that restricting aminoglycosides to amikacin only resulted in increasing Gram-negative resistance although there was no significant effect on patient outcome.

Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Jun, 28(6), 843 - 51
{Usefulness of a protease inhibitor (urinastatin) in ARDS with infectious diseases}; Kawai S et al.; The usefulness of urinastatin (UST) for adult respiratory distress syndrome (ARDS) induced by gram-negative sepsis was evaluated in clinical and experimental studies . Twelve cases of clinical septic ARDS were treated with combination therapy of UST and methylprednisolone (M-PSL) . Ten out of 12 responded favorably . This result was considered to some extent to be better than that of our previous experience with single administration of M-PSL for patients with septic ARDS . Pathophysiologic experiments on UST in endotoxic status were then performed . Immediately after the intravenous administration of endotoxin to rats, serum levels of beta-glucuronidase and elastase released from PMNs were increased and pulmonary edema was observed at 48-hours after the endotoxin injection . Various degrees of pulmonary edema were also observed by the intravenous administration of beta-glucuronidase and PMNs-elastase . These changes induced by the endotoxin were significantly inhibited by the intraperitoneal administration of UST, and they were inhibited more by the combination therapy of UST and M-PSL . In an in vitro study, significantly large amounts of beta-glucuronidase and elastase were released from PMNs by incubating human PMNs with endotoxin . By adding UST to this system, the release of these PMNs proteases was inhibited . These results suggested that UST neutralizes the PMNs-elastase release in the status endotoxemics, and consequently resulted in a better prognosis in cases of septic ARDS.

J Bioenerg Biomembr, 1990 Jun, 22(3), 473 - 91
The mechanism of secretion of hemolysin and other polypeptides from gram-negative bacteria; Holland IB et al.; In the secretion of polypeptides from Gram-negative bacteria, the outer membrane constitutes a specific barrier which has to be circumvented . In the majority of systems, secretion is a two-step process, with initial export to the periplasm involving an N-terminal signal sequence . Transport across the outer membrane then involves a variable number of ancillary polypeptides including both periplasmic and outer membrane . While such ancillary proteins are probably specific for each secreted protein, the mechanism of movement across the outer membrane is unknown . In contrast to these systems, secretion of the E . coli hemolysin (HlyA) has several distinctive features . These include a novel targeting signal located within the last 50 or so C-terminal amino acids, the absence of any periplasmic intermediates in transfer, and a specific membrane-bound translocator, HlyB, with important mammalian homologues such as P-glycoprotein (Mdr) and the cystic fibrosis protein . In this review we discuss the nature of the HlyA targeting signal, the structure and function of HlyB, and the probability that HlyA is secreted directly to the medium through a trans-envelope complex composed of HlyB and HlyD.

J Bioenerg Biomembr, 1990 Jun, 22(3), 233 - 69
Signal peptide mutants of Escherichia coli; Gennity J et al.; Numerous secretory proteins of the Gram-negative bacteria E . coli are synthesized as precursor proteins which require an amino terminal extension known as the signal peptide for translocation across the cytoplasmic membrane . Following translocation, the signal peptide is proteolytically cleaved from the precursor to produce the mature exported protein . Signal peptides do not exhibit sequence homology, but invariably share common structural features: (1) The basic amino acid residues positioned at the amino terminus of the signal peptide are probably involved in precursor protein binding to the cytoplasmic membrane surface . (2) A stretch of 10 to 15 nonpolar amino acid residues form a hydrophobic core in the signal peptide which can insert into the lipid bilayer . (3) Small residues capable of beta-turn formation are located at the cleavage site in the carboxyl terminus of the signal peptide . (4) Charge characteristics of the amino terminal region of the mature protein can also influence precursor protein export . A variety of mutations in each of the structurally distinct regions of the signal peptide have been constructed via site-directed mutagenesis or isolated through genetic selection . These mutants have shed considerable light on the structure and function of the signal peptide and are reviewed here.

Anal Biochem, 1990 Jun, 187(2), 281 - 91
Amino and hydrazino alkyl benzoates as derivatizing agents for the separation and mass spectrometric analysis of oligosaccharides from bacterial lipooligosaccharides; John CM et al.; In an attempt to develop more sensitive and versatile methods for the structure analysis of oligosaccharides derived from lipooligosaccharides (LOS) of gram-negative bacteria, amino and hydrazino alkyl benzoate derivatives were prepared . These oligosaccharide derivatives were separated by HPLC and then analyzed by liquid secondary ion mass spectrometry (LSIMS) . Both the amino and hydrazino alkyl benzoates react with the free reducing termini of acid-treated LOS, increasing the hydrophobicity of the released oligosaccharides and allowing them to be separated by reverse-phase HPLC . In addition, these oligosaccharide derivatives now contain a sensitive uv chromophore for subsequent peak detection and improve the quality of the LSIMS spectra compared to underivatized oligosaccharides . However, the amino alkyl benzoates reacted poorly compared to the analogous hydrazino alkyl benzoates with 3-deoxy-manno-2-keto octulosonic acid (KDO), and oligosaccharides with KDO at the reducing terminus, especially when the oligosaccharide also contained phosphoethanolamine . Derivatization with the hydrazino compounds can be carried out quickly and under mild conditions using a minimal amount of reagent, and is therefore suitable for microscale analyses . The chromatographic and mass spectrometric characteristics of these derivatives make them excellent alternatives to permethylation and peracetylation techniques for the structural analysis of complex bacterial oligosaccharides derived from glycolipids.

J Clin Microbiol, 1990 Jun, 28(6), 1163 - 8
Use of two-dimensional gas chromatography with electron-capture detection for the measurement of lipopolysaccharides in peritoneal fluid and plasma from rats with induced peritonitis; Sonesson A et al.; The content of 3-hydroxymyristic acid from Escherichia coli lipopolysaccharide in peritoneal fluid and plasma from rats was determined by two-dimensional gas chromatography with electron-capture detection of the 3-O-pentafluorobenzoyl methyl ester derivative . The detection limit of lipopolysaccharide in peritoneal fluid was 3 ng/ml . An experimental model of E . coli peritonitis in the rat was used, with and without coinjection of bile . The concentrations of lipopolysaccharide were highest in both peritoneal fluid and plasma samples from rats injected with E . coli and bile, reaching a maximum 1 h after injection by the gas chromatographic method . Corresponding Limulus assay results for peritoneal samples showed a small increase of lipopolysaccharide concentrations during the first 4 h after injection, followed by a substantial increase . The results indicate that bile salts cause an increased release of lipopolysaccharide from gram-negative bacterial cells in vivo and that this may be responsible for the high mortality caused by peritonitis . In contrast to the Limulus assay, gas chromatography enables the total amount of lipopolysaccharide in a clinical sample to be determined.

Hepatology, 1990 Jun, 11(6), 916 - 22
Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice; Cornell RP et al.; A hypothesis has been proposed by this laboratory that endogenous gut-derived lipopolysaccharide is responsible for systemic endotoxemia in animals with acute liver injury particularly after partial (67%) hepatectomy . Systemic lipopolysaccharide and possibly fibrin aggregates or tissue debris then elicit release of cytokines from phagocytizing macrophages and/or monocytes that may be essential for normal liver regeneration . To test this hypothesis liver regeneration was assessed in germ-free euthymic mice that lack the gram-negative bacterial source of lipopolysaccharide, as well as being deficient in lymphoid tissue and relatively resistant to endotoxin . To complement the germ-free animals, conventional athymic nude BALB/c mice and conventional lipopolysaccharide-resistant C3H/HeJ mice were also examined . Liver regeneration, quantified by {3H} thymidine incorporation into hepatic DNA after partial hepatectomy was performed on mice anesthetized with ether, was significantly depressed in germ-free euthymic and conventional athymic BALB/c mice and delayed in conventional lipopolysaccharide-resistant C3H/HeJ mice, as compared with conventional control BALB/c and C3H/HeN animals . Pretreatment of conventional euthymic control mice with lipopolysaccharide 24 hr before surgery significantly stimulated hepatic DNA synthesis after 67% liver resection . Germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice pretreated with endotoxin did not manifest significant stimulation of liver regeneration . Evidence is reviewed that cytokine release in response to endotoxin was depressed in germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice as compared with conventional euthymic controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Otol Rhinol Laryngol Suppl, 1990 Jun, 148, 35 - 8
Outer hair cells as potential targets of inflammatory mediators; Huang M et al.; Inner ear sequelae with temporary or permanent sensorineural hearing loss can result from inflammatory processes in the middle ear . Loss of outer hair cells in the base of the cochlea has been noted in otitis media, but it is not known how this damage occurs . Evidence supports the permeability of the round window membrane to substances mediating inflammation in the middle ear, and the presence of white blood cells has been reported in the perilymph . In the present study, the potential cytotoxic effects of two representative inflammatory mediators, endotoxin and free radicals, have been evaluated by use of short-term culture of isolated outer hair cells from the guinea pig cochlea model . Incubation with endotoxins from two gram-negative pathogens increased the rate of hair cell death fourfold to sixfold . Free radicals (generated by exposure of cells to UV light or by excitation of intracellular fluorescent dyes) produced morphologic damage to hair cells within 60 seconds . These latter effects were delayed by addition of free-radical scavengers . It is concluded that inflammatory mediators are cytotoxic to hair cells and therefore are potentially ototoxic if permeating the round window membrane.

Oral Microbiol Immunol, 1990 Jun, 5(3), 162 - 5
Three-dimensional structure of the surface layer of Wolinella recta; Dokland T et al.; The three-dimensional structure of the crystalline surface layer (S-layer) of Wolinella recta ATCC 33238T, a gram-negative, anaerobic periodontopathogen, was determined to 3.8 nm resolution by electron microscopy and digital image processing . The S-layer protein is closely associated with the outer bacterial membrane, and shows p6 symmetry with lattice spacing and thickness of 21 nm and 15 nm, respectively . The funnel-shaped subunits consist of 6 heavy domains located round a common base at the sixfold axis, and communicate with the adjacent subunits through a lighter domain at the threefold axis (M6C3 arrangement).

Mol Microbiol, 1990 Jun, 4(6), 873 - 80
Structure and function of haemolysin B,P-glycoprotein and other members of a novel family of membrane translocators; Blight MA et al.; Recent studies have identified two sub-families of highly conserved polypeptides in a wide variety of organisms concerned with the transport of many different compounds, specific for each transport protein . Both families, represented by HisP and HlyB, respectively, have in common a highly conserved, approximately 25 kD domain, containing an ATP-binding site . The HisP sub-family essentially consists of cytoplasmic proteins which couple energy to the import of small substrates through cytoplasmic membrane permeases in Gram-negative bacteria . The HlyB (P-glycoprotein) sub-family, on the other hand, contains a second large domain which apparently acts as the transmembrane translocator itself, which in most cases drives the secretion of a variety of compounds . These membrane domains share a number of structural features which also serve to distinguish these proteins as a closely related group . Nevertheless, the compounds secreted by the HlyB sub-family include large polypeptides, polysaccharides and a variety of anti-tumour drugs . We describe here the properties of each of these remarkable proteins and we speculate on their possible mechanism of action.

Wien Klin Wochenschr, 1990 May 25, 102(11), 329 - 33
{Clinical efficacy and nephrotoxicity of gentamicin in single-dose parenteral administration of total individually adapted daily dosage}; Huber G et al.; The efficacy of gentamicin given intravenously once daily in a single, individually-adapted dose in form of a short infusion was confirmed in 30 patients with febrile urogenitary infections, taking nephrotoxicity into consideration . Antibiotic therapy was given for 7 days in each case, the individual dose of gentamicin being chosen from the dosage schedule according to Mawer . Depending on weight, age and renal function we used daily doses ranging from 160 to 480 mg (i.e . 2 to 5 mg/kg) of gentamicin . All patients were cured and all gram-negative bacteria were eliminated; no nephrotoxicity was recorded, as verified by constantly low serum levels of gentamicin (below the recommended peak level of 2 micrograms/ml) and non-significant changes in serum creatinine level . According to our results and to the findings of other investigations cited in the literature we conclude that in gentamicin therapy the once-daily individually--adapted intravenous dosage regimen is superior to to continuous administration by means of repeated daily doses with regard to efficacy and absence of nephrotoxicity.

Schweiz Med Wochenschr, 1990 May 19, 120(20), 738 - 41
{Cat-scratch disease}; Schadelin J; Cat scratch disease is a self-limited but chronic lymphadenitis which has acquired new interest by the description of a responsible pathogen, an intracellularly located gram-negative rod . Due to its low pathogenicity for laboratory animals, the definite proof for causality is still lacking . Severe systemic courses, mainly in immune suppressed patients, can however be identified more positively by detection of this pathogen . A routine diagnostic test is likely to be developed in the near future and therapeutic guidelines for the minority of severe, progressive forms may be drawn up.

Biochemistry, 1990 May 15, 29(19), 4734 - 9
Respiratory-driven Na+ electrical potential in the bacterium Vitreoscilla; Efiok BJ et al.; Vitreoscilla is a Gram-negative bacterium with unique respiratory physiology in which Na+ was implicated as a coupling cation for the generation of a transmembrane electrical gradient (delta psi) . Thus, cells respiring in the presence of 110 mM Na+ generated a delta psi of -142 mV compared to only -42 and -56 mV for Li+ and choline, respectively, and even the -42 and -56 mV were insensitive to the protonophore 3,5-di-tert-butyl-4-hydroxybenzaldehyde (DTHB) . The kinetics of delta psi formation and collapse correlated well with the kinetics of Na+ fluxes but not with those of H+ fluxes . Cyanide inhibited respiration, Na+ extrusion, and delta psi formation 81% or more, indicating that delta psi formation and Na+ extrusion were coupled to respiration . Experiments were performed to distinguish among three possible transport systems for this coupling: (1) a Na(+)-transporting ATPase; (2) an electrogenic Na+/H+ antiport system; (3) a primary Na+ pump directly driven by the free energy of electron transport . DCCD and arsenate decreased cellular ATP up to 86% but had no effect on delta psi, evidence against a Na(+)-transporting ATPase . Low concentrations of DTHB had no effect on delta psi; high concentrations transiently collapsed delta psi, but led to a stimulation of Na+ extrusion, the opposite of that expected for a Na+/H+ antiport system . Potassium ion, which collapses delta psi, also stimulated Na+ extrusion . The experimental evidence is against Na+ extrusion by mechanisms 1 and 2 and supports the existence of a respiratory-driven primary Na+ pump for generating delta psi in Vitreoscilla.

Arch Biochem Biophys, 1990 May 15, 279(1), 54 - 9
Purification, partial characterization, and possible role of catalase in the bacterium Vitreoscilla; Abrams JJ et al.; Vitreoscilla is a gram-negative bacterium that contains a unique bacterial hemoglobin that is relatively autoxidizable . It also contains a catalase whose primary function may be to remove hydrogen peroxide produced by this autoxidation . This enzyme was purified and partially characterized . It is a protein of 272,000 Da with a probable A2B2 subunit structure, in which the estimated molecular size of A is 68,000 Da and that of B, 64,000 Da, and an average of 1.6 molecules of protoheme IX per tetramer . The turnover number for its catalase activity was 27,000 s-1 and the Km for hydrogen peroxide was 16 mM . The peroxidase activity measured using o-dianisidine was 0.6% that of the catalase activity . Cyanide, which inhibited both catalase and peroxidase activities, bound the heme in a noncooperative manner . Azide inhibited the catalase activity but stimulated the peroxidase activity . An apparent compound II was formed by the reaction of the enzyme with ethyl hydrogen peroxide . The enzyme was reducible by dithionite, and the ferrous enzyme reacted with CO . The cellular content of Vitreoscilla hemoglobin varies during the growth cycle and in cells grown under different conditions, but the ratio of hemoglobin to catalase activity remained relatively constant, indicating possible coordinated biosynthesis and supporting the putative role of Vitreoscilla catalase as a scavenger of peroxide generated by Vitreoscilla hemoglobin.

Am J Med, 1990 May 14, 88(5A), 2S - 8S
A descriptive study of 42 cases of Branhamella catarrhalis pneumonia; Wright PW et al.; PURPOSE: We studied the clinical and laboratory findings of patients with pneumonia due to Moraxella (Branhamella) catarrhalis to better characterize the types of patients who develop this pneumonia, the clinical features of the illness, and the type of and response to drug therapy, as well as the immediate and long-term survival of these patients . PATIENTS AND METHODS: Patients with sputum samples that met cellular criteria as quality samples and that grew B . catarrhalis as the sole pathogen were identified retrospectively from microbiology records at a regional referral hospital for cardiac and pulmonary diseases . Records of these patients were reviewed to identify patients with radiographic findings of pneumonia . Clinical and laboratory characteristics of these patients were then studied in detail . RESULTS: Forty-two patients who met the criteria for B . catarrhalis pneumonia were identified . Most patients were elderly (over 65 years; 55 percent), malnourished (69 percent), and had severe chronic obstructive pulmonary disease or another serious underlying disease (98 percent) . The seasonal incidence of this pneumonia was October through April (88 percent), with the annual number of cases having increased since 1982 . The clinical presentation was typically mild . Interstitial or mixed interstitial-alveolar infiltrates superimposed on pre-existing chronic lung disease was the most common radiographic finding . Approximately 90 percent of sputa were acceptable for Gram stain and contained 10 to more than 50 gram-negative cocci/1,000 x field . All cultures produced a heavy growth of B . catarrhalis, with 67 percent of strains positive for beta-lactamase . No patient had identified bacteremia (zero of 25 tested) . Therapy with numerous agents including cefotaxime, amoxicillin/clavulanic acid, and trimethoprim/sulfamethoxazole resulted in a good clinical and bacteriologic response . However, 45 percent of patients died of their underlying diseases on this admission or within three months . CONCLUSION: These findings provide a good profile of B . catarrhalis pneumonia . Despite the mild character of the illness, the pneumonia occurs in patients with end-stage pulmonary or malignant disease and almost 50 percent of patients die of their underlying diseases within three months.

Arzneimittelforschung, 1990 May, 40(5), 611 - 3
Penetration of ciprofloxacin into the spinal fluid in patients with viral and bacterial meningitis; Trautmann M et al.; Cerebrospinal fluid (CSF) concentrations of ciprofloxacin (Ciprobay) were measured by high performance liquid chromatography (HPLC) in 20 patients with varying degrees of meningeal inflammation . Underlying clinical syndromes were viral meningitis (n = 10), convalescent phase of acute bacterial meningitis (n = 9), and acute phase of bacterial meningitis (n = 1) . CSF concentrations following an intravenous dose of 200 mg ranged between 0.028 and 0.11 mg/l (5.8-26.8% of corresponding serum levels) in patients with viral meningitis, and between 0.049 and 0.389 mg/l (5.9-77.0% of corresponding serum levels) in patients with bacterial meningitis . Taken together with the findings of other authors, the results indicate a potential usefulness of ciprofloxacin as an alternative agent for treatment of meningitis due to susceptible gram-negative microorganisms.

Methods Find Exp Clin Pharmacol, 1990 May, 12(4), 287 - 90
Concentration of cefixime in bile, gallbladder wall and serum after preoperative administration in patients undergoing cholecystectomy; Moorthi K et al.; Cefixime is a new oral cephalosporin antibiotic with improved activity against Gram-negative pathogens comparable to the parenteral third generation cephalosporins, high beta-lactamase stability and a long elimination half-life of about 3 h . 15 patients undergoing cholecystectomy received 2 x 200 mg/day cefixime for two days before surgery . The last application was administered 13-17 h preoperatively . Intraoperatively, the mean biliary level of cefexime was 199.3 micrograms/ml (8.8 micrograms/ml-1163.8 micrograms/ml) . The mean level in gallbladder wall was 25.02 micrograms/g (0.68 micrograms/g-61.20 micrograms/g) . Serum samples were taken simultaneously . Despite relevant concentrations in bile and gallbladder wall, no cefixime could be detected in the serum samples of two patients . The other 13 patients, however, showed relevant serum levels between 0.28 micrograms/ml and 2.98 micrograms/ml (mean 1.01 micrograms/ml) . Side effects as well as an influence on laboratory parameters were not seen . After administration of cefixime in bile and gallbladder tissue high antibiotic levels were achieved, even 13-17 hours after the last application.

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