Biochim Biophys Acta, 1988 Mar 22, 939(1), 102 - 10 Interactions between a paramagnetic analogue of cholesterol and filipin; Maurin L et al.; A paramagnetic analogue of cholesterol (called 25-doxyl-27-norcholesterol (CNO)), labeled near the w-end of the hydrophobic tail, was used to study interactions of cholesterol with filipin . We observed by electron microscopy that CNO- and cholesterol-filipin complexes are structurally equivalent . Two kinds of complexes were seen by ESR spectroscopy and electron microscopy, depending on the stoichiometric R ratio between the antibiotic and sterol . When R was high, an immobilized ESR spectrum appeared, showing strong imbrication between CNO and filipin . When R was nearer to unity, an exchange-broadened spectrum emerged, corresponding to a new phase that was very rich in CNO (a fast exchange between spins could occur by nearest contacts) . CNO was easily displaced from its complex (i) by gradual addition of genuine cholesterol; and (ii) by an excess of phospholipids, owing to the very poor affinity of CNO (and cholesterol, by extension) for filipin in the lipidic phase . Almost no difference appeared between the ESR spectra of oriented samples, i.e . the probe showed no long-range order in any complex of CNO with filipin. CMAJ, 1988 Mar 15, 138(6), 503 - 10 Chronic obstructive pulmonary disease; Anthonisen NR; Outpatient management of chronic obstructive pulmonary disease (COPD) is reviewed in this paper . Smoking cessation is probably important, although its benefit in established COPD is unproven . Bronchodilator therapy may be of more than symptomatic benefit and is indicated in virtually all patients . Specific beta 2-agonists are the most widely used agents and can be given in substantially larger doses than are usually recommended . Ipratropium bromide, an anticholinergic drug, is about as effective as a beta 2-agonist, but in large doses the two drugs do not seem to have additive effects, unlike theophylline and beta 2-agonists . Systemic corticosteroids decrease airway obstruction substantially in a small number of patients with COPD; these agents should be reserved for these patients and used sparingly . Inhaled steroids are of little benefit, as are respiratory stimulants and depressants . Broad-spectrum antibiotic therapy helps to relieve symptomatic exacerbations of COPD, particularly those characterized by increased dyspnea, sputum volume and sputum purulence . Cor pulmonale is best managed by diuretics and oxygen, with digoxin reserved for left ventricular failure and supraventricular arrhythmias . Continuous oxygen therapy at home is indicated for the patients who have chronic arterial hypoxemia. Biochemistry, 1988 Mar 8, 27(5), 1744 - 51 NMR studies of echinomycin bisintercalation complexes with d(A1-C2-G3-T4) and d(T1-C2-G3-A4) duplexes in aqueous solution: sequence-dependent formation of Hoogsteen A1.T4 and Watson--Crick T1.A4 base pairs flanking the bisintercalation site; Gao XL et al.; We report on two-dimensional proton NMR studies of echinomycin complexes with the self-complementary d(A1-C2-G3-T4) and d(T1-C2-G3-A4) duplexes in aqueous solution . The exchangeable and nonexchangeable antibiotic and nucleic acid protons in the 1 echinomycin per tetranucleotide duplex complexes have been assigned from analyses of scalar coupling and distance connectivities in two-dimensional data sets recorded in H2O and D2O solution . An analysis of the intermolecular NOE patterns for both complexes combined with large upfield imino proton and large downfield phosphorus complexation chemical shift changes demonstrates that the two quinoxaline chromophores of echinomycin bisintercalate into the minor groove surrounding the dC-dG step of each tetranucleotide duplex . Further, the quinoxaline rings selectively stack between A1 and C2 bases in the d(ACGT) complex and between T1 and C2 bases in the d(TCGA) complex . The intermolecular NOE patterns and the base and sugar proton chemical shifts for residues C2 and G3 are virtually identical for the d(ACGT) and d(TCGA) complexes . A change in sugar pucker from the C2'-endo range to the C3'-endo range is detected at C2 on formation of the d(ACGT) and d(TCGA) complexes . In addition, the sugar ring protons of C2 exhibit upfield shifts and a large 1 ppm separation between the H2' and H2" protons for both complexes . The L-Ala amide protons undergo large downfield complexation shifts consistent with their participation in intermolecular hydrogen bonds for both tetranucleotide complexes.(ABSTRACT TRUNCATED AT 250 WORDS) Poult Sci, 1988 Mar, 67(3), 493 - 501 Subcutaneous glucose is more advantageous in establishing the posthatch poult than oral administration; Moran ET Jr; Poults have been shown to have low carbohydrate reserve after hatching, and glucose at this time improves early performance . Present experimentation examined the effects of .5 mL of 50% glucose in saline 2 h after subcutaneous injection (s.c.) at the base of the head or given as an oral gavage . Timing of administration and slaughter corresponded to when poults would encounter antibiotic-vitamin injection at the hatchery and the subsequent stress of transportation . Live weight after treatments was greater for poults given s.c . glucose than those untreated, whereas oral dosing led to a loss in weight . This weight loss could be wholly attributed to decreased carcass moisture . The s.c . glucose increased yolk sac resorption, and s.c . and oral glucose improved accretion of crude protein and ether extract by the yolk sac and liver-free carcass . Liver glycogen and blood glucose increased to a greater extent from s.c . than from oral glucose . Loss of body water after oral glucose and the poults' reduced efficacy in improving carbohydrate status might be attributed to an immature intestine. Poult Sci, 1988 Mar, 67(3), 434 - 9 Improved growth in the progeny of hens immunized with jackbean urease; Pimentel JL et al.; Three experiments were conducted with Single Comb White Leghorn and broiler breeder hens . Half of the experimental hens were injected with jackbean urease enzyme and the other half served as uninjected or adjuvant-injected controls . Chicks hatched from urease-injected or control hens were placed factorially (2 x 2) on diets with or without antibiotics . Urease injection of hens resulted in significant improvements in percent fertility and hatch compared with values for control hens . Depending on age, both urease injection and antibiotic feeding stimulated chick growth, independently of one another . Additive effects of these treatments resulted in significant improvements in body weight of chicks injected with urease and consuming antibiotics at all time periods compared with body weights of untreated controls. Biochem Cell Biol, 1988 Mar, 66(3), 177 - 83 Effect of the aggregation state of amphotericin B on its interaction with ergosterol; Gruda I et al.; The interaction of amphotericin B with ergosterol was studied in aqueous solutions of propanol . The mode of the interaction was found to be related to the aggregation state of amphotericin B . Ergosterol does not react (or reacts extremely slowly) with monomeric amphotericin B . Traces of a small aggregate, probably a dimer, enable a cooperative reaction . At high concentrations of the dimer, the reaction is immediate and the concentration of amphotericin B complexed with ergosterol is twice as high as the amount of added sterol . The interaction with ergosterol is hindered when the antibiotic is in micellar form . The pharmaceutical form, Fungizone, behaves similarly to the pure amphotericin B . Fungizone's greater solubility in water does not modify either the extent or the mode of interaction with ergosterol. Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Mar, 267(4), 531 - 6 Degradation of acylaminopenicillins with regard to their pH dependency; Knoller J et al.; Determination of antibiotic concentration is performed in many biological fluids and tissues which all have different pH values . Therefore, we investigated the in vitro stability of three acylaminopenicillins (azlocillin, mezlocillin and piperacillin) in borate buffer by the HLPC technique with regard to pH dependency . HPLC allows the detection of all three substances together with their metabolites, penicilloate and penilloate, within 15 min . Decomposition was monitored at 37 degrees C during a 24 h incubation period (pH values ranged between pH 3.0 and 10.0) . The highest degradation rates were observed with a buffer solution of pH = 10.0: 50% of the azlocillin and 83% of the mezlocillin were decomposed after 8 h while under the same conditions, piperacillin was completely decomposed already after 1 h . The highest stability was detected in borate buffer at pH values of 4.0, 5.0, and 6.0 . At pH = 3.0, degradation was determined as follows: 31% of the piperacillin, 39% of the mezlocillin, and 45% of the azlocillin were decomposed after 24 h . Penilloic acid was identified as the main metabolite in contrast to buffer solutions with higher pH values which only revealed negligible amounts of this compound. Antibiot Khimioter, 1988 Mar, 33(3), 190 - 6 {The protoplasts of Acremonium chrysogenum . Biochemical and morphological studies}; Telesnina GN et al.; A procedure for preparing stable A . chrysogenum protoplasts capable of 60 per cent regeneration was developed . Two morphogenetic types of the regeneration were detected . The variants isolated after the protoplast regeneration were characterized by wide ranges of morphological variation . Capacity for the antibiotic production varied from 60 to 160 per cent of the activity of the starting strain . A procedure for isolating functionally active mitochondria from protoplasts of A . chrysogenum was also developed . Their main bioenergetic parameters were studied . In the respiratory chain of the A . chrysogenum mitochondria there were detected three conjugation sites of oxidative phosphorylation. No Shinkei Geka, 1988 Mar, 16(3), 297 - 302 {Bacterial intracranial aneurysms associated with infectious endocarditis--report of 3 cases}; Umezu H et al.; Three cases of bacterial intracranial aneurysms associated with infective endocarditis are reported . All of the patients were successfully treated by various combinations of cardiac surgery, neurosurgery and chemotherapy with antibiotics . Case 1: A 39-year-old female was admitted with the complaint of sudden onset of severe headache following persistent fever of several month's duration . CT scan revealed a left frontal old hematoma and angiography detected an aneurysm located in the frontal ascending branch of the left middle cerebral artery . After 2 weeks' antibiotic therapy, the second angiography showed the aneurysm to be decreased in size . The third angiography, performed 2 weeks after cardiac valve replacement for infective endocarditis, demonstrated complete resolution of the aneurysm . Case 2: A 19-year-old male entered hospital with high fever and chills . In addition to infective endocarditis, CT scan and angiography revealed an aneurysm arising from the distal portion of the left posterior cerebral artery . The patient was treated with high dose antibiotics and then his general condition improved . However, angiography examined 4 weeks after the initial study demonstrated the aneurysm to be apparently enlarged . Therefore, the aneurysm was excised before cardiac surgery . Repeated angiography after valve replacement showed no further aneurysm . Case 3: A 30-year-old female was admitted on the diagnosis of infective endocarditis and meningitis . CT scan showed abnormal density areas in the right frontal lobe and the left temporal lobe.(ABSTRACT TRUNCATED AT 250 WORDS) J Antibiot (Tokyo), 1988 Mar, 41(3), 360 - 5 Effect of B-factor and its analogues on rifamycin biosynthesis in Nocardia sp; Kawaguchi T et al.; B-Factor, 3'-(1-butylphosphoryl)adenosine, which was isolated from yeast extract, is an inducer of rifamycin production in a rifamycin non-producing Nocardia mutant . Feeding of B-factor to the mutant culture demonstrated that the induction process was triggered during early stationary phase . Rifamycin production in the mutant was also induced by an exogenous supply of 3-amino-5-hydroxybenzoic acid, an intermediate of the antibiotic pathway, suggesting that a step upstream from the intermediate is regulated by B-factor . B-Factor analogues, i.e., alkylesters of 3'-AMP with alkyl side chains of C(2) approximately C(12) and n-butyl esters of 3'-GMP and 2'-AMP all showed the B-factor activity . Among these n-octyl ester of 3'-AMP showed the lowest effective concentration of approximately 3 x 10(-10) M . An intrinsic substance of the Nocardia sp . with potent B-factor activity and a UV absorption maximum at 260 nm was isolated from the cells of the parental strain. Pediatr Emerg Care, 1988 Mar, 4(1), 5 - 8 Clinical indicators for lumbar puncture; Rosenberg NM et al.; This study was conducted to demonstrate that experienced pediatricians using standard clinical indications for performing a lumbar puncture should have a higher yield of positive spinal taps than previously reported and also can detect bacterial meningitis . These indicators included temperature elevation, inability to be consoled, level of alertness, nuchal rigidity, bulging fontanel, decreased appetite, rash, referral, and febrile seizures . Eighty-two of 381 (22%) lumbar punctures were positive for pleocytosis and/or organisms . Patients were divided into two groups, consisting of those with one indicator (low risk) and those with greater than one indicator (high risk) . Thirteen of 14 patients with bacterial meningitis were placed in the high risk group . The single patient in the low risk group had been pretreated with antibiotics . The positive predictive value in bacterial meningitis for a score greater than one was 5% . The average number of clinical indicators in bacterial meningitis was 3.7, versus 2.4 in viral meningitis and 1.6 without meningitis . These findings suggest that, in the absence of prior antibiotic therapy, an experienced pediatrician can clinically detect patients at high risk for bacterial meningitis . Nonbacterial meningitis cannot be as readily detected clinically. Pediatr Infect Dis J, 1988 Mar, 7(3), 160 - 4 Outpatient therapy of serious pediatric infections with ceftriaxone; Bradley JS et al.; Convalescent outpatient parenteral antibiotic therapy with ceftriaxone was evaluated in an uncontrolled study of 101 children with documented serious bacterial infections, including meningitis . Criteria for outpatient therapy were established to assure that risks of complications from the illness were minimal at the time of discharge from the hospital . Daily physician visits and motivated, capable parents were considered essential in outpatient management . Ceftriaxone was given once daily to children with non-central nervous system infections and once or twice daily intravenously to children with meningitis . The mean durations of therapy for children with non-central nervous system infections and with meningitis were 2.4 and 4.6 days, respectively . No child enrolled in this study was readmitted to the hospital for medical or social reasons . Probable complications of treatment included diarrhea in 13% of children with meningitis and in 6% of children with non-central nervous system infections . One child with meningitis developed pseudomembranous colitis . For children who are infected with bacteria that are highly susceptible to ceftriaxone, single daily dose outpatient therapy is a reasonable option for management if a good clinical response to initial treatment is demonstrated and the risks of complications of the disease process are negligible. J Clin Microbiol, 1988 Mar, 26(3), 429 - 32 Risk factors for candidemia in cancer patients: a case-control study; Karabinis A et al.; Risk factors for candidemia were analyzed in a case-control study of 30 cancer patients with candidemia and 58 controls . In a univariate analysis, previous surgery, neutropenia, central catheterization, chemotherapy, specific antibiotic treatments, and peripheral cultures positive for Candida spp . were associated with a significantly increased risk of candidemia . In a multivariate logistic model, the significant risk factors for candidemia were positive peripheral cultures for Candida spp . (P = 0.02), central catheterization (P = 0.03), and neutropenia (P = 0.05) . These results should help to identify cancer patients with a high risk of candidemia, who should be given early systemic antifungal therapy. Br J Haematol, 1988 Mar, 68(3), 345 - 50 Transient platelet and HLA antibody formation in multitransfused patients with malignancy; McGrath K et al.; Fifty-nine patients receiving platelet transfusions for bone marrow failure secondary to malignancy were screened at regular intervals for the presence of antibodies to human leucocyte (HLA) and platelet specific antigens . HLA antibodies occurred in 19 patients, 10 of whom also developed platelet specific antibodies . The HLA antibodies disappeared in 10 of 15 patients followed for periods of 2-14 months . In two patients this occurred whilst still receiving platelet transfusions . Antibody reappeared in only two of six patients subsequently transfused . Antibodies to platelet specific antigens were detected in 28 patients . They were transient, often appeared in association with infection, and in 50% of cases tested demonstrated autoantibody activity . There was no association with antibiotic drug therapy, or PFA/EDTA-dependent cryptantigens . Platelet recovery at 1 h or 20 h post transfusion was not significantly reduced in the presence of platelet specific antibodies . These findings have important implications for the selection of platelet donors for alloimmunized recipients. J Med Chem, 1988 Mar, 31(3), 590 - 603 Stereoelectronic factors influencing the biological activity and DNA interaction of synthetic antitumor agents modeled on CC-1065; Warpehoski MA et al.; The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described . Many of these synthetic analogues are significantly more effective than 1 against murine tumors . In particular, compound 27 exhibits high activity and potency . Structure-activity analysis supports a molecular mechanism for biological action involving hydrophobic interaction of the drug with DNA and acid-catalyzed alkylation of DNA. J Med Chem, 1988 Mar, 31(3), 583 - 90 One- and two-dimensional 1H NMR, fluorescence, and molecular modeling studies on the tomaymycin-d(ATGCAT)2 adduct . Evidence for two covalent adducts with opposite orientations and stereochemistries at the covalent linkage site; Cheatham S et al.; Tomaymycin is a member of the pyrrolo{1,4}benzodiazepine antitumor-antibiotic group that binds covalently to the exocyclic 2-amino group of guanine in DNA . Previous correlation of fluorescence and NMR data suggested that the 11R,11aS and the 11S,11aS diastereomers of tomaymycin could bind to DNA in two orientations relative to the covalently modified guanine (Barkley, M . D.; Cheatham, S.; Thurston, D . E.; Hurley, L . H . Biochemistry 1986, 25, 3021-3031) . We now report on fluorescence, one- and two-dimensional proton NMR, and molecular modeling studies of the tomaymycin-d(ATGCAT)2 adduct, which corroborate these earlier observations . Fluorescence measurements show that there are two species of tomaymycin bound to d(ATGCAT)2, which are tentatively identified as the 11R,11aS and 11S,11aS diastereomers . Two distinct sets of signals for the tomaymycin molecule are present in the proton NMR spectrum of the tomaymycin-d(ATGCAT)2 duplex adduct . Two-dimensional correlation spectroscopy (2D-COSY) studies also show connectivities for four cytosine H5-H6 and eight thymine methyl-H6 protons and thus clearly establish the presence of two distinct species of tomaymycin-d(ATGCAT)2 adducts in solution . A single scalar 11-11a 1H NMR coupling in the 2D-COSY spectrum is indicative of an adduct species that has an S configuration at the C-11 position . Two-dimensional nuclear Overhauser effect (NOESY) spectra of the tomaymycin-d(ATGCAT)2 duplex adduct show that the adducts are relatively nondistortive . In a NOESY experiment, cross-peaks were identified between both the aromatic H9 proton and the ethylidine methyl protons of tomaymycin and two different adenine H2 protons of d(ATGCAT)2 . Molecular mechanics calculations with AMBER show that the two species with the thermodynamically most favorable binding energies are the 11R,11aS and 11S,11aS isomers with their aromatic rings to the 5' and 3' sides of the covalently bound guanine, respectively . The NOEs observed between tomaymycin protons and adenine H2 protons are in accord with molecular modeling studies . Taken together, these results strongly suggest that the two forms of tomaymycin bound to d(ATGCAT)2 are the 11S,11aS and 11R,11aS species, oriented with their aromatic rings to the 3' and 5' sides, respectively, of the covalently modified guanines. Blood, 1988 Mar, 71(3), 811 - 4 High-efficiency gene transfer and expression in normal human hematopoietic cells with retrovirus vectors; Laneuville P et al.; Retroviral vectors containing the selectable bacterial gene for G418 resistance (neo) were used to demonstrate gene transfer into primary human bone-marrow progenitor cells . To obtain populations of cells in which a high proportion of cells were expressing the neo gene, several important modifications were made to earlier procedures . Cells from normal donors were infected in vitro, were exposed to high concentrations of G418 for two days in liquid culture to enrich for cells expressing the neo gene, and were plated in semisolid medium . Gene transfer and expression were detected in colonies arising from progenitors of granulocyte-macrophage and erythroid lineages . Survival curves indicated that a high proportion of progenitor cells, approaching 100%, were G418 resistant . Furthermore, addition of growth factors contained in 5637-conditioned medium to the bone marrow improved the recovery of G418-resistant progenitors twofold to threefold . In addition to these biological measurements of gene expression in progenitor cells, significant levels of neo-specific RNA, similar to the levels of RNA expression in the virus-producing fibroblast cell line, were detected in the bone marrow cells after preselection . These results demonstrate that retrovirus vectors can be used successfully to transfer genes at high efficiency into progenitor cells in the human blood-forming system. J Bacteriol, 1988 Mar, 170(3), 1168 - 74 New loci required for Streptomyces coelicolor morphological and physiological differentiation; Champness WC; Streptomyces coelicolor colonies differentiate both morphologically, producing aerial spore chains, and physiologically, producing antibiotics as secondary metabolites . Single mutations, which block both aspects of differentiation, define bld (bald colony) genes . To identify new bld genes, mutagenized colonies were screened for blocks in the earliest stage of sporulation, the formation of aerial mycelia, and blocks in antibiotic synthesis . The mutations in 12 mutants were mapped; in each strain, the pleiotropic phenotype was due to a single mutation . Seven of the strains contained mutations in known bld loci, bldA and bldB . Three strains contained mutations in a new locus, bldG, and two contained mutations in another new locus, bldH . Like the previously defined bldA mutants, the bldG and bldH mutants were developmentally blocked on glucose . On a variety of carbon sources whose utilization was subject to glucose repression, the developmental blocks were partially relieved for bldG (and bldA) mutants and fully relieved for bldH mutants . These results are compatible with an hypothesis which suggests that there are two alternative controls on S . coelicolor differentiation, one of which is glucose repressible. Clin Orthop, 1988 Mar, (228), 117 - 22 Cefazolin versus cefamandole for prophylaxis during total joint arthroplasty; Bryan CS et al.; A prospective, randomized, double-blind comparison of cefazolin versus cefamandole was carried out to evaluate safety and efficacy and to determine bone and serum antibiotic concentrations in patients undergoing total joint arthroplasty . Dosages were 1 g of cefazolin before surgery followed by 500 mg every eight hours for six doses, versus 2 g of cefamandole before surgery followed by 1 g every eight hours for six doses . Intraoperative doses were given during prolonged procedures . No significant adverse drug reactions were clearly attributable to either drug . Among 48 patients receiving cefazolin there was one postoperative wound infection and one distant site infection . Among 49 patients receiving cefamandole, there were two postoperative wound infections and two distant site infections . No deep wound infections occurred in either group during at least 48 months of follow-up study . In hip specimens removed at surgery, the mean antibiotic concentrations were 1.6 +/- 1.4 micrograms/g for cefazolin recipients, compared with 5.7 +/- 5.9 micrograms/g for cefamandole recipients (p less than .001) . In knee specimens, the mean antibiotic concentrations were 0.64 +/- 0.57 microgram/g for cefazolin recipients compared to 3.8 +/- 3.4 micrograms/g for cefamandole recipients (p = .004) . Cefazolin given at one-half the dose of cefamandole appeared to be equally safe and effective but resulted in lower bone concentrations of antibiotic. J Vet Pharmacol Ther, 1988 Mar, 11(1), 56 - 62 Effect of induced synovial inflammation on pharmacokinetics and synovial concentration of sodium ampicillin and kanamycin sulfate after systemic administration in ponies; Firth EC et al.; Single doses of sodium ampicillin (10 mg/kg) and kanamycin sulfate (5 mg/kg) were administered intramuscularly (i.m.) separately, and then together, to five pony mares . The plasma antibiotic concentration-time curves were constructed . The pharmacokinetic parameters of the antibiotics given separately were not altered by concurrent administration . Four of the five pony mares were then given the i.m . kanamycin/ampicillin combination 4 h after acute synovitis and fever had been induced by injection of lipopolysaccharide into the left intercarpal joint . The plasma concentration-time curves and the synovial concentration-time curves of inflamed and normal joints were constructed . The Cmax of ampicillin in the lipopolysaccharide experiment was significantly higher than in the other experiments . The antibiotics entered the synovial fluid of the inflamed joints more quickly and attained higher concentrations than in the uninflamed joints . The ampicillin concentration exceeded 5 micrograms/ml in inflamed synovial fluid for some 2.5 h after injection, and kanamycin sulfate concentration exceeded 2 micrograms/ml for 7 h. Antibiot Khimioter, 1988 Mar, 33(3), 180 - 5 {The methods of protoplast formation and transformation of Streptomyces strains}; Furs AR et al.; Factors influencing formation, regeneration and transformation of protoplasts in streptomyces are described . Conditions for formation and regeneration of protoplasts in 4 industrial strains producing the macrolide antibiotic tylosin were studied . It was demonstrated possible to apply the method for transformation of the S . lividans type culture to 3 industrial strains of S . griseus producing grisin, an antibiotic used as a feed additive . Potential increasing of the efficiency of protoplast transformation and transfection in various actinomycetous strains including industrial ones is discussed . The stimulating effect of lyposomes on transformation of protoplasts in S . lividans 66 with DNA of plasmids pVG101 and pIJ350 as well as transfection with DNA of phages SH10 and KS404 was shown . The tylosin resistance genes in S . fradiae strain B45 were cloned which enabled isolating the cluster of the genes participating in tylosin biosynthesis. J Antibiot (Tokyo), 1988 Mar, 41(3), 366 - 72 Myomycin: mode of action and mechanism of resistance; Davies J et al.; Myomycin is an unusual pseudodisaccharide antibiotic with a beta-lysyl oligopeptide ester side chain that has structural similarities with kasugamycin, streptomycin and streptothricin . We show that the mode of action of myomycin in vivo and in vitro closely resembles that of streptomycin; in addition, spontaneous myomycin-resistant mutants of Escherichia coli are essentially indistinguishable from streptomycin-resistant mutants at the rRNA and r-protein level . Myomycin is not a substrate for the known streptomycin-modifying enzymes and could be useful in the characterization of natural streptomycin-resistant isolates and in counterselecting against the presence of streptomycin-modifying enzymes . The relationship between structure and inhibition of protein synthesis has been examined for a series of derivatives of myomycin. Biochem Pharmacol, 1988 Mar 1, 37(5), 827 - 36 Quantitative structure-activity relationships in amphotericin B derivatives; Cheron M et al.; The quantitative structure-activity relationships studies of amphotericin B and its 16 semisynthetic derivatives obtained by modification at carboxyl and amino groups have been done . The results of five biological tests were subjected to principal component analysis, a numerical method useful in the investigation of large sets of data . For some compounds, also, interaction with lipidic vesicles was investigated by spectroscopic methods . The results obtained indicate that: (i) The presence of positively charged nitrogen atom (protonable or bearing fixed charge) is indispensable for biological activity and antibiotic-sterol interaction; (ii) The lack of free carboxyl group in the molecule favours the differentiation between cholesterol and ergosterol containing cells. Ontogenez, 1988 Mar-Apr, 19(2), 213 - 7 {Effect of trophoblast-specific beta 1-glycoprotein on the ratio of cellular forms in a mast cell population}; Sidorov NM et al.; The influence of trophoblast-specific beta 1-glycoprotein (TSG) on the degranulation of mast cells and their saturation with heparin was studied . Introduction of the TSG into the population of mast cells of the rat peritoneal fluid practically does not change their degranulation, but lowers the degree of their saturation with heparin . An antibiotic alone increases the saturation of the cells with heparin . The serum of an allergic animal markedly stimulates the degranulation and lowers the degree of saturation of the mast cells with heparin . In an experimental model (antibiotic--the serum of the allergic mast cells) the mast cells transform into very clear (heparin-free) cells and the degree of saturation is at minimum . The TSG introduction into this system stabilizes the population of mast cells and markedly increases the degree of their saturation with heparin . Although the degranulation is rather intensive, it is less expressed, than in the experimental model . This suggests the presence of TSG receptors on the mast cells (targets of allergic reactions) . The possibility to use TSG preparations in the therapy of allergic diseases is discussed. Jpn J Surg, 1988 Mar, 18(2), 136 - 41 Ceftizoxime level in the myocardium (right atrial muscle and mitral papillary muscle) during open heart surgery; Kobayashi M et al.; We determined the level of sodium ceftizoxime (CZX) in the right atrium and mitral papillary muscle of 22 adults and 6 children undergoing open-heart surgery, 60 and 120 minutes after intravenous administration of this drug at the dosages of 2 grams for adults and 1 gram for children . The CZX level in the right atrial muscle after 60 minutes was 37.0 micrograms/g in adults and 51.0 micrograms/g in children . The CZX level in the papillary muscle of the mitral valve, determined at 120 minutes was 16.9 micrograms/g . In the present study, we measured the level of the antibiotic CZX in the myocardial tissue during open-heart surgery . The purpose of this was to determine the quantity in which the antibiotic is taken into the myocardial tissue. Infect Dis Clin North Am, 1988 Mar, 2(1), 131 - 47 The runny nose . Infection of the paranasal sinuses; Daley CL et al.; Infection of the paranasal sinuses is an important although infrequent complication of the common cold . This article discusses the pathophysiology, etiology, clinical presentation, complications, differential diagnosis, treatment, and prevention of these infections . Proper treatment with the appropriate antibiotic may help in avoiding irreversible mucosal damage, thus decreasing the incidence of chronic sinusitis. Prim Care, 1988 Mar, 15(1), 187 - 99 Acute pancreatitis; Blake RL Jr; Acute pancreatitis is most often secondary to prolonged excessive alcohol intake or biliary tract disease . The diagnosis is based on a combination of physical, laboratory, and radiologic findings . Differentiation from intra-abdominal processes that require surgical intervention is important . Treatment involves restoration of intravascular volume, correction of hypoxemia and metabolic derangements, and resting the gastrointestinal tract . Prognostic indicators are useful in identifying severe cases that may benefit from more aggressive monitoring, peritoneal lavage, antibiotic therapy, and surgical intervention . The recovery period may be complicated by sequellae of pancreatic necrosis and by sepsis. J Clin Neuroophthalmol, 1988 Mar, 8(1), 35 - 8 Subjective oscillopsia ("jiggling" vision) presumably due to aminoglycoside ototoxicity . A report of two cases; Marra TR et al.; Following aminoglycoside antibiotic therapy, two patients developed self-limited subjective oscillopsia in the absence of a detectable ocular motility disturbance (nystagmus or opsoclonus) . Oscillopsia represents a rare, but highly distressing symptom resulting from disruption of the vestibulo-ocular reflex, producing profound illusory movement of the visual environment . Although the differential diagnosis includes vascular, inflammatory, and structural disorders impacting on either the central or peripheral projections of this brainstem reflex, iatrogenic aminoglycoside ototoxicity was the likely explanation in the two patients presented . Ways of minimizing the risk of aminoglycoside toxicity are briefly reviewed. Clin Immunol Immunopathol, 1988 Mar, 46(3), 360 - 7 Transient T-cell abnormality in a selective IgM-immunodeficient patient with Brucella infection; Raziuddin S et al.; We describe here one 9-year-old female patient with an unusual form of selective IgM and CD4+ (OKT4+) helper/inducer T-cell immunodeficiency associated with Brucella infection . During the acute phase of Brucella infection, the percentage of infection . During the acute phase of Brucella infection, the percentage of peripheral blood lymphocytes (PBL) displaying OKT3+, OKT11+, and OKT4A+ phenotypes was decreased, and that of the OKT8+ cell was increased . These phenotypic T-cell abnormalities disappeared after antibiotic therapy in a 5-week period . However, the marked deficiency of CD4+ T cells and the IgM deficiency present during the acute phase of illness remained after recovery from illness . In vitro immunoglobulin production experiments during the acute phase of illness demonstrated that the patient's T cells lacked the capacity to provide helper/inducer function for normal B-cell differentiation to secrete IgM . The patient's T cells were also shown to possess IgM-specific suppressor cell activity on normal B- and T-cell differentiations . Thus impaired T-cell function was shown to be responsible for IgM-deficient antibody production . Defective interleukin 2 receptor expression and production by the patient's PBL in response to mitogenic stimulation also were present, indicating a severe defect in the patient's T-cell function. Neurol Res, 1988 Mar, 10(1), 2 - 6 Freeze-fracture cytochemistry of cholesterol content in neuronal plasma membrane following cerebral ischaemia; Cuevas P et al.; Minor changes on the neuronal perikaryon cytoplasm and large alterations in neuronal processes have been demonstrated with transmission electron microscopy after 60 minutes of focal and selective cerebral ischaemia . The distribution of cholesterol in neuronal plasma membrane and perikarya plasmalemma of normal and ischaemic caudate nucleus was investigated with the polyene antibiotic filipin, a morphological probe for membrane cholesterol domains in freeze-fracture replicas . After filipin incubation of prefixed vibratome slices, filipin-cholesterol complexes appeared as 20-30 proturberances and pits on P- and E-faces . Distinct patterns of filipin-cholesterol complexes were found in non-ischaemic and ischaemic neuronal membrane . The filipin-treated specimens showed a 35-40% drop in cholesterol content in the neuronal plasmalemma one hour after cerebral ischaemia. Eur J Haematol, 1988 Mar, 40(3), 273 - 8 Chromosomes, Auer rods and prognosis in acute myeloid leukaemia; Billstrom R et al.; We have analysed survival time and complete remission (CR) rate after induction treatment including cytosine arabinoside and an anthracycline antibiotic in 94 patients with acute myeloid leukaemia, comparing the results in four different groups according to the presence or absence of Auer rods and the presence (AN/AA) or absence (NN) of abnormal cytogenetic clones at diagnosis . The finding of Auer rods was a positive prognostic factor with respect to CR rate (p less than 0.02) and survival time (p less than 0.02) irrespective of the cytogenetic pattern . The AN/AA pattern was associated with lower CR rate (p less than 0.05) and 6-months survival (p = 0.05) in the 49 Auer rod-negative patients . In the 45 patients with Auer rods, no significant differences in CR rate or survival were seen between AN/AA and NN patients . We conclude that the negative prognostic impact of chromosome abnormalities in acute myeloid leukaemia might be restricted to Auer rod-negative disease. Blood, 1988 Mar, 71(3), 717 - 22 Gene transfer into hematopoietic progenitor cells from normal and cyclic hematopoietic dogs using retroviral vectors; Eglitis MA et al.; The Moloney murine leukemia retrovirus-derived vector N2 was used to transfer the bacterial NeoR gene (conferring resistance to the neomycin analogue G418) into hematopoietic progenitor cells . Approximately 5% of day seven CFU-GM were resistant to 2,000 micrograms/ml G418, using a supernatant infection protocol in the absence of vector-producing cells . A greater proportion of CFU-GM colonies were recovered relative to uninfected controls as the stringency of selection was diminished . Enzyme activity was detected in drug-resistant colonies, confirming that the resistant colonies obtained after infection with N2 represented cells producing neomycin phosphotransferase . Activity in the CFU-GM colonies approached 50% of that of drug-resistant vector-producing cells on a per cell basis . To test the hypothesis that more rapidly cycling bone marrow cells would be more susceptible to vector infection, we treated progenitor cells obtained from cyclic hematopoietic (CH) dogs with the N2 vector . Despite the increased numbers of hematopoietic progenitor cells obtained from CH dogs, the proportion of G418-resistant CFU-GM did not increase over that obtained with N2-infected normal marrow . These results demonstrate that retroviral vectors can be used to transfer and express exogenous genes in canine hematopoietic progenitor cells. Pflugers Arch, 1988 Mar, 411(3), 243 - 51 Na transport stimulation by novobiocin: transepithelial parameters and evaluation of ENa; Rick R et al.; The action of the antibiotic novobiocin on transepithelial Na transport was studied in isolated skins obtained from two different frog species . In Rana esculenta addition of novobiocin to the outer bath (1 mM) resulted in a sustained and reversible stimulation of the short-circuit current, transepithelial potential, and transepithelial conductance . Similar, though more variable and much less pronounced changes were observed in Rana temporaria . In the presence of amiloride (0.1 mM) novobiocin had no effect on any of the investigated transport parameters and all novobiocin induced changes were fully reversed when amiloride was given subsequently . At reduced external Na concentration or low pH the action of novobiocin was found to be greatly attenuated . In the presence of novobiocin an increased affinity to amiloride and a linearization of the transepithelial current-voltage relationship was observed . The results are consistent with the view that novobiocin increases the Na permeability of the outer membrane, possibly by an attenuation of an Na self-inhibition mechanism . In addition, the driving force of transepithelial Na transport was estimated by means of novobiocin . Several different methods were employed, providing varying results . As shown in an Appendix, for the most part the discrepancies can be explained by changes in the intracellular Na and K concentration . In some cases, novobiocin induced large secondary increases in the skin conductance which can be referred to an increased Cl permeability. Ann Plast Surg, 1988 Mar, 20(3), 280 - 4 Pyoderma gangrenosum and progressive cutaneous ulceration; Rand RP et al.; Pyoderma gangrenosum is a cutaneous disorder characterized by slowly progressive ulceration which is refractory to local wound care and antibiotic therapy . The diagnosis is made after the exclusion of other causes of cutaneous ulceration . The cause of pyoderma is thought to be a deficiency in host immune reactivity, and a systemic illness is present in 80% of patients . High-dose corticosteroids and appropriate treatment of the underlying disease represent the mainstays of therapy, although hyperbaric oxygen has recently shown promise in the healing of skin grafts over these lesions. Mutat Res, 1988 Mar, 193(2), 157 - 65 Bleomycin and X-ray-hypersensitive Chinese hamster ovary cell mutants: genetic analysis and cross-resistance to neocarzinostatin; Robson CN et al.; We have previously reported the isolation of 3 mutants of Chinese hamster ovary cells which exhibit hypersensitivity to bleomycin . 2 mutants were isolated on the basis of bleomycin-sensitivity {designated BLM-1 and BLM-2, Robson et al., Cancer Res., 45 (1985) 5304-5309} and 1 as adriamycin-sensitive {ADR-1, Robson et al., Cancer Res., 47 (1987) 1560-1565} . Because bleomycin generates DNA-strand breaks via a free-radical mechanism, we have studied the survival response of these mutants to a range of drugs which also generate free radicals and consequently DNA-strand breaks . The mutants are all hypersensitive to phleomycin, which differs from bleomycin in being unable to intercalate due to a modified bithiazole moiety . However, BLM-2 cells alone are hypersensitive to pepleomycin, a semi-synthetic bleomycin analogue . In contrast, BLM-1 cells are more sensitive than BLM-2 to streptonigrin (which operates via a hydroquinone intermediate) . ADR-1 cells show wild-type resistance to streptonigrin . The results obtained with neocarzinostatin, an antibiotic requiring thiol activation, are unusual in that both BLM-1 and BLM-2 are approximately 3-fold more resistant than parental cells . However, the steady-state intracellular level of the major non-protein thiol, glutathione, is not altered in BLM-1 or BLM-2 cells . ADR-1 cells show essentially wild-type resistance to neocarzinostatin . Analysis of cell hybrids shows that BLM-1 and BLM-2 cells are phenotypically recessive in combination with parental CHO-K1 cells and represent different genetic complementation groups not only from one another, but also from the bleomycin-sensitive mutant xrs-6, isolated on the basis of X-ray sensitivity by Jeggo and Kemp {Mutation Res., 112 (1983) 313-319} . These results indicate that at least 3 gene products are involved in cellular protection against bleomycin toxicity in mammalian cells. Wien Med Wochenschr, 1988 Feb 29, 138(4), 75 - 80 {Differential diagnostic significance of C-reactive protein in meningoencephalitis}; Koppi S et al.; The assessment of C-reactive protein (CRP) serum levels is very specific and sensitive with respect to differential diagnosis between viral and bacterial meningoencephalitis . Its validity surpasses by far all other parameters having been in use up to now . We could prove this with an investigation comprising 43 patients . It appears to be reasonable to include the assessment of CRP serum levels in the routine methods of neurological differential diagnostics . It is simple and offers a quick primary information as well as a regular evaluation of the effect of antibiotic therapy in the course of treatment. FEBS Lett, 1988 Feb 29, 229(1), 49 - 53 Stimulation and inhibition of human platelet membrane high-affinity GTPase by neomycin; Herrmann E et al.; The effect of the inositol phospholipid-binding antibiotic neomycin was studied on high-affinity GTPase in human platelet membranes . At low concentrations (up to 1 mM), neomycin by itself stimulated a high-affinity GTPase . This GTPase stimulation was additive with that caused by the hormonal factors, prostaglandin E1 and epinephrine, but not with thrombin . At concentrations higher than 1 mM, neomycin reduced control GTPase activity and eliminated the stimulation caused by thrombin . The data suggest that neomycin by a presently unknown mechanism can regulate activity states of signal transducing GTP-binding proteins. Arch Biochem Biophys, 1988 Feb 15, 261(1), 148 - 60 Purification and characterization of tryptophan dioxygenase from Streptomyces parvulus; Hitchcock MJ et al.; Tryptophan dioxygenase, derived from Streptomyces parvulus, was purified to near homogeneity and shown to have a native Mr of 88,000 . Kinetic parameters of the enzyme were determined and evidence suggesting that it is a hemoprotein was obtained . Tryptophan dioxygenase has a high specificity toward L-tryptophan with an apparent Km of 0.3 mM . L-3-Hydroxykynurenine was a competitive inhibitor with respect to L-tryptophan with a Ki of 0.16 mM . In vitro, the enzyme displayed little activity in the absence of a reducing agent; ascorbate, at 50 mM, was the preferred reductant providing almost a 50-fold increase in enzyme activity . The regulation of tryptophan dioxygenase synthesis and activity is described . The expression of the enzyme is correlated with the biosynthesis of actinomycin D in S . parvulus . These results support the hypothesis that tryptophan dioxygenase functions as the first enzyme in the sequence converting L-tryptophan to the chromophore of this antibiotic. Am J Ophthalmol, 1988 Feb 15, 105(2), 198 - 202 Effects of gentamicin on healing of transdifferentiating conjunctival epithelium in rabbit eyes; Alfonso E et al.; We examined the effects of commercially prepared gentamicin, a wide-spectrum topical antibiotic, on the healing of epithelial defects of the rabbit cornea . Abrasions were created by: (1) removing the corneal epithelium and 3 mm of the conjunctival epithelium (Group 1); and (2) producing the same initial trauma and subsequently removing the central 8 mm of epithelium 28 days after initial healing (Group 2) . The complete healing of the large corneal and conjunctival epithelial defects was not delayed when gentamicin solution was used four times a day (Group 1) . When the healed epithelium was reinjured while transdifferentiating from conjunctival to corneal epithelium (day 28, Group 2), treatment with the gentamicin solution and its vehicle, both containing benzalkonium chloride, delayed epithelial healing significantly compared with treatment with saline (P less than .01). Cancer Res, 1988 Feb 15, 48(4), 775 - 8 Therapeutic attack of hypoxic cells of solid tumors: presidential address; Sartorelli AC; Hypoxic cells of solid tumors are relatively resistant to therapeutic assault . Studies have demonstrated that oxygen-deficient tumor cells exist in an environment conducive to reductive reactions making hypoxic cells particularly sensitive to bioreductive alkylating agents . Mitomycin C, the prototype bioreductive alkylating agent available for clinical use, is capable of preferentially killing oxygen-deficient cells both in vitro and in vivo . This phenomenon is at least in part the result of differences in the uptake and metabolism of mitomycin C by hypoxic and oxygenated tumor cells, with the ultimate critical lesion being the cross-linking of DNA by the mitomycin antibiotic . The combination of mitomycin C with X-irradiation, to attack hypoxic and oxygenated tumor cell populations, respectively, has led to enhanced antitumor effects in mice bearing solid tumor implants and in patients with cancer of the head and neck . More efficacious kill of hypoxic tumor cells may be possible by the use of dicoumarol in combination with mitomycin or by the use of the related antibiotic porfiromycin . The findings support the use of an agent with specificity for hypoxic tumor cells in potentially curative regimens for solid tumors. Biochim Biophys Acta, 1988 Feb 10, 952(3), 297 - 303 Inactivation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase by koningic acid; Sakai K et al.; Koningic acid, a sesquiterpene antibiotic, is a specific inhibitor of the enzyme glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) . In the presence of 3 mM of NAD+, koningic acid irreversibly inactivated the enzyme in a time-dependent manner . The pseudo-first-order rate constant for inactivation (kapp) was dependent on koningic acid concentration in saturate manner, indicating koningic acid and enzyme formed a reversible complex prior to the formation of an inactive, irreversible complex; the inactivation rate (k 3) was 5.5.10(-2) s-1, with a dissociation constant for inactivation (Kinact) of 1.6 microM . The inhibition was competitive against glyceraldehyde 3-phosphate with a Ki of 1.1 microM, where the Km for glyceraldehyde 3-phosphate was 90 microM . Koningic acid inhibition was uncompetitive with respect to NAD+ . The presence of NAD+ accelerated the inactivation . In its absence, the charcoal-treated NAD+-free enzyme showed a 220-fold decrease in apparent rate constant for inactivation, indicating that koningic acid sequentially binds to the enzyme next to NAD+ . The enzyme, a tetramer, was inactivated when maximum two sulfhydryl groups, possibly cysteine residues at the active sites of the enzyme, were modified by the binding of koningic acid . These observations demonstrate that koningic acid is an active-site-directed inhibitor which reacts predominantly with the NAD+-enzyme complex. Biochemistry, 1988 Feb 9, 27(3), 893 - 901 Recognition and repair of the CC-1065-(N3-adenine)-DNA adduct by the UVRABC nucleases; Tang MS et al.; The recognition and repair of the helix-stabilizing and relatively nondistortive CC-1065-(N3-adenine)-DNA adduct by UVRABC nuclease has been investigated both in vivo with phi X174 RFI DNA by a transfection assay and in vitro by a site-directed adduct in a 117 base pair fragment from M13mp1 . CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis which binds within the minor groove of DNA through N3 of adenine . In contrast to the helix-destabilizing and distortive modifications of DNA caused by ultraviolet light or N-acetoxy-2-(acetylamino)fluorene, CC-1065 increases the melting point of DNA and decreases the S1 nuclease activity . Using a viral DNA-Escherichia coli transfection system, we have found that the uvrA, uvrB, and uvrC genes, which code for the major excision repair proteins for UV- and NAAAF-induced DNA damage, are also involved in the repair of CC-1065-DNA adducts . In contrast, the uvrD gene product, which has been found to be involved in the repair of UV damage, has no effect in repairing CC-1065-DNA adducts . Purified UVRA, UVRB, and UVRC proteins must work in concert to incise the drug-modified phi X174 RFI DNA . Using a site-directed and multiple CC-1065 modified (MspI-BstNI) 117 base pair fragment from M13mp1, we have found that UVRABC nuclease incises at the eighth phosphodiester bond on the 5' side of the CC-1065-DNA adduct on the drug-modified strand.(ABSTRACT TRUNCATED AT 250 WORDS) S Afr Med J, 1988 Feb 6, 73(3), 186 - 7 Infective endocarditis in pregnancy . A report of 3 cases; Dommisse J; Three pregnant patients with infective endocarditis presented with haematuria . The importance of this symptom is stressed and a brief review of immune-complex glomerulonephritis is given . The role of antibiotic therapy in preventing infective endocarditis is discussed. S Afr Med J, 1988 Feb 6, 73(3), 185 - 6 Bacterial aneurysm of the intracavernous carotid artery secondary to suppurative otitis media . A case report; du Plessis JJ et al.; A case of an intracavernous carotid aneurysm, with ophthalmoplegia, secondary to cavernous sinus thrombophlebitis is reported . The necessity of angiography when this condition persists despite adequate antibiotic therapy is stressed. J Toxicol Sci, 1988 Feb, 13(1), 49 - 59 Effects of rokitamycin on young rats with hyperbilirubinemia--determination of unbound and brain bilirubin levels and examination for localized yellow discoloration of brain tissue; Yamamura H et al.; The effects of rokitamycin (RKM), a macrolide antibiotic, on young rats with hyperbilirubinemia were investigated . RKM at a dose of 1,000 mg/kg was orally administered to 14-day-old rats with hereditary, non-hemolytic hyperbilirubinemia (homozygous Gunn rats, total plasma bilirubin concentration: about 7 mg/dl) . Animals given 10 ml/kg of 0.5% carboxymethyl cellulose (CMC) were used as control . Plasma total bilirubin concentration, plasma unbound bilirubin concentration and cerebellar bilirubin level did not significantly change during 1, 3, 6 and 24 hours after administration of RKM or CMC . There was no significant difference in plasma total bilirubin concentration, plasma unbound bilirubin concentration and cerebellar bilirubin level between RKM-treated and control animals at 1, 3, 6 and 24 hours after the administration . No localized yellow discoloration of the brain tissue (non-cerebellar parts) was noted at 1, 3, 6 and 24 hours after administration of either RKM or CMC. Jpn J Antibiot, 1988 Feb, 41(2), 201 - 9 {Pharmacokinetic and clinical studies on ceftriaxone in the perinatal period}; Yamamoto T et al.; The pharmacokinetics of ceftriaxone (CTRX) and its clinical efficacy in perinatal infections were studied . The obtained results are summarized as follows . 1 . Concentrations of CTRX in maternal serum, umbilical cord serum and amniotic fluid were determined following intravenous injection with 1 g of CTRX . Maternal serum levels were not lower than 100 micrograms/ml immediately after administration, and gradually decreased to about 10 micrograms/ml in 12 hours, and to 4 micrograms/ml in 24 hours . The half-life of CTRX in maternal serum was 5.6 hours . CTRX levels in umbilical cord serum were about 7 micrograms/ml at 10 minutes after injection, increasing to 12 to 13 micrograms/ml in 12 hours and decreasing to 5 micrograms/ml in 24 hours . CTRX levels in amniotic fluid were slightly lower than those in the umbilical cord serum, and about 2 micrograms/ml at 10 minutes after injection, and they remained at 4 to 8 micrograms/ml thereafter for 28 hours . 2 . CTRX (1 g) was intravenously administered twice daily to 9 patients with perinatal infections for 3 to 7 days . Clinical efficacies of CTRX were judged excellent in 2 cases and good in 7, suggesting that CTRX was effective in all cases . No side effects or laboratory abnormalities were observed in any case . As a result of these findings, CTRX may be considered a very useful antibiotic in perinatal infections. J Antibiot (Tokyo), 1988 Feb, 41(2), 202 - 6 The molecular basis of kirromycin (mocimycin) action; a 1H NMR study using deuterated elongation factor Tu; Barber J et al.; The binding of the antibiotic kirromycin (mocimycin) to its target protein, bacterial elongation factor Tu (EF-Tu), has been studied by 1H NMR spectroscopy using deuterated protein . Narrow lines were observed in the spectrum of the unbound protein (due to residual protons) and in the spectrum of the kirromycin-EF-Tu complex . The spectrum of the complex has been compared with the spectra of the unbound protein and the unbound drug, and the results are interpreted in terms of the mode of antibiotic action of kirromycin. Am J Surg, 1988 Feb, 155(2), 361 - 5 Effect of cephalosporins on fascial healing after celiotomy; Scher KS et al.; A 7 day course of either cefonicid or cefazolin significantly reduced mean wound breaking weight after midline celiotomy in Sprague-Dawley rats compared with control animals . This detrimental effect was not seen when each drug was administered as a single preoperative dose . Even a 3 day course of cefonicid was associated with a significant reduction in the weight required to disrupt a healing abdominal closure . An increased incidence of incisional hernias was also noted among animals treated for 7 days with cefonicid or cefazolin . Shorter antibiotic regimens were not associated with an increased frequency of incisional herniation. J Urol, 1988 Feb, 139(2), 359 - 61 Malacoplakia: a case involving epididymis and a case involving a bladder complicated by calculi; Dubey NK et al.; We report the sixth case of malacoplakia of the epididymis in the world literature and the first to occur in a patient who had undergone a vasectomy previously . The patient was treated successfully by epididymectomy . Another case of malacoplakia of the bladder is reported in which multiple adherent stones developed on the surface of the lesion . Long-term antibiotic therapy led to stabilization of bilateral obstruction at the ureterovesical junction. Plast Reconstr Surg, 1988 Feb, 81(2), 229 - 32 The diagnosis of osteomyelitis in patients with pressure sores; Lewis VL Jr et al.; A prospective blind trial was undertaken to assess the usefulness of commonly used tests to diagnose osteomyelitis underlying pressure sores . Sixty-one pressure sores were studied, with a histopathologic diagnosis from the ostectomy specimen being available in 52 . White cell count, erythrocyte sedimentation rate, plain pelvic x-ray, technetium-99m bone scan, computerized tomography, and Jamshidi needle bone biopsy were studied . The most useful individual test was a needle bone biopsy, with a sensitivity of 73 percent and a specificity of 96 percent . Technetium-99m bone scans and computerized tomography are not indicated in the diagnosis of osteomyelitis associated with pressure sores . Plain pelvic x-ray, white cell count, and erythrocyte sedimentation rate, with a diagnosis of osteomyelitis if any test is positive, is the most sensitive (89 percent), specific (88 percent), noninvasive workup . Jamshidi needle biopsy may be useful where these tests are negative and a clinical suspicion of osteomyelitis remains . Extent of surgical debridement and antibiotic therapy can then be rationally decided on the basis of this information. Clin Pharm, 1988 Feb, 7(2), 109 - 16 Rocky Mountain spotted fever; Kamper CA et al.; The epidemiology, pathogenesis, clinical features, and treatment of Rocky Mountain spotted fever are reviewed . Rocky Mountain spotted fever is a severe infection caused by Rickettsia rickettsii transmitted to man by various species of ticks . High-incidence areas exist in the southeast and south central United States . Only 60-70% of patients with the disease report a history of tick bite or exposure to tick-infested areas . The disease is initially characterized by fever, headache, gastrointestinal complaints, myalgia, and a generalized rash . In several days generalized vasculitis may lead to periorbital edema and nonpitting edema of the face and extremities . Central nervous system involvement is common . Because signs and symptoms associated with the disease are nonspecific, the diagnosis is often delayed or missed . Traditionally diagnostic confirmation relied on serologic testing, but an indirect fluorescent antibody assay will soon be commercially available . Rocky Mountain spotted fever is usually treated with the rickettsiostatic agents chloramphenicol or tetracycline, but few comparative data on these agents in patients with the disease are available . For patients who cannot tolerate oral medications, intravenous chloramphenicol sodium succinate is the preferred treatment; chloramphenicol is also the drug of choice for children less than eight years of age . Otherwise, oral tetracycline hydrochloride is the drug of choice . Antibiotic therapy should be continued for 7-10 days or until the patient is afebrile for two to five days . All cases of Rocky Mountain spotted fever must be reported to the Centers for Disease Control . The best ways to decrease the morbidity and mortality of the disease are to increase awareness of its signs and symptoms and to prevent exposure to ticks. Emerg Med Clin North Am, 1988 Feb, 6(1), 43 - 56 The red eye; Howes DS; The patient with a red eye constitutes a very common clinical problem encountered in the Emergency Department setting . Conjunctivitis, the most common cause of the red eye, generally is not associated with disturbance of vision or associated ocular pain . If either of these symptoms is present, a more serious disorder must be suspected . Treatment of infectious conjunctivitis is guided by interpretation of a Gram's stain and subsequent culture of any exudate present . Initial treatment of most cases includes use of topical antibiotic and local comfort measures . Complications of infectious conjunctivitis include more invasive disease such as keratitis or abscess formation, with potential corneal perforation and destruction . All patients should be referred for ophthalmologic followup, both to assess adequacy of treatment and to treat unexpected complications . Remember that allergic conjunctivitis is a common condition that responds to antihistamine decongestant medications given orally or topically . Occasionally these conditions are caused by self-prescribed use of ocular medication, and discontinuation of all eye medication is required . Corticosteroid eye drops are rarely indicated and should be used only at the direction of an ophthalmologist . When the diagnosis is uncertain, treatment is best withheld, as "shotgun" therapy is seldom beneficial. Am Fam Physician, 1988 Feb, 37(2), 283 - 92 Infected diabetic foot ulcers; Amin NM; Infections of diabetic foot ulcers are a common, longstanding complication of poorly controlled diabetes . They result from the interplay of peripheral neuropathy and peripheral vascular disease . In most cases, diabetic foot infections are polymicrobial, and deep tissue culture after debridement is essential for identifying the true pathogens . Treatment includes bed rest, empiric and specific antibiotic therapy, and good control of diabetes. Am J Hematol, 1988 Feb, 27(2), 144 - 5 Adverse reactions to trimethoprim-sulfamethoxazole in hemophiliacs; Nahum K et al.; Adverse reactions to trimethoprim-sulfamethoxazole are very prevalent in patients with acquired immunodeficiency syndrome (AIDS) . Recently we have observed severe toxicities associated with trimethoprim-sulfamethoxazole in three hemophiliacs, a group known to be at risk for developing AIDS . At the time of these reactions to the antibiotic, none of the patients had yet manifested any stigmata of AIDS per se . We advise caution in the use of trimethoprim-sulfamethoxazole in hemophiliacs and other patients at high risk for the development of AIDS. Biochimie, 1988 Feb, 70(2), 259 - 65 Is the three-site model for the ribosomal elongation cycle sound? Baranov VI, Ryabova LA. The release of deacylated tRNA from the ribosome as a result of translocation has been studied . Translating ribosomes prepared with poly(U)-S-S-Sepharose columns have been used . It has been shown that deacylated tRNA released from the ribosomal P site as a result of translocation rebinds with the vacated A site . Consistent with the known properties of the A site of the ribosome, this interaction is reversible, Mg2+-dependent, codon-specific and is inhibited by the antibiotic tetracycline . It has been concluded that the proposed three-site model of the ribosomal elongation cycle (Rheinberger and Nierhaus (1983) Proc . Natl . Acad . Sci . USA 80, 4213-4217) is not sound: the experimentally observed 'retention' of the deacylated tRNA on the ribosome after translocation can be explained by a codon-dependent rebinding to the A site, rather than by its transition to the 'E site', i.e., in terms of the classical two-site model. Arch Biochem Biophys, 1988 Feb 1, 260(2), 561 - 8 Synthesis of the cyanogenic beta-glucosidase, linamarase, in white clover; Dunn MA et al.; The beta-glucosidase, linamarase, which specifically hydrolyzes cyanogenic substrates, linamarin and lotaustralin, in white clover, is synthesized in the early stages of leaf and seedling development in genetically competent plants . Plants, from natural populations, possessing at least one Li allele synthesize linamarase but plants with only li alleles do not, nor do they produce inactive but antigenically related linamarase . Linamarase is known to be a mannosyl glycoprotein, which in its active form is a dimer, with a subunit size of 62,000 Mr . We demonstrate that the antibiotic tunicamycin, which prevents N-acetyl-asparagine linked glycosylation, reduces in vivo synthesis of linarmarase . In vitro translation of mRNA from a Li Li plant yields a 59,000 Mr immunoprecipitated linamarase polypeptide which is modified to a 62,000 Mr product by the addition of dog pancreas microsomes . No anti-linamarase immunoprecipitable product is obtained from the in vitro translation products of mRNA from a li li plant. Epidemiol Infect, 1988 Feb, 100(1), 101 - 9 Red-cell IgM-antibody capture assay for the detection of Mycoplasma pneumoniae-specific IgM; Coombs RR et al.; A red-cell IgM-antibody capture assay has been developed for detecting Mycoplasma pneumoniae-specific IgM, which is based on the adsorption or 'capture' of IgM from patients' sera onto so-called 'inagglutinable' bovine red cells, chemically linked with anti-human mu . When M . pneumoniae antigen is added to the system, the red cells agglutinate in the presence of M . pneumoniae-specific IgM . The test was compared with the mu-capture ELISA described by Wreghitt & Sillis (1985), and was found to give comparable results . The two tests had similar sensitivity and specificity and could detect M . pneumoniae-specific IgM for a similar time (up to 6 months) after proven M . pneumoniae infection . However, the red-cell antibody capture assay is a much more simple and rapid test, taking only 1 h to perform (compared to 24 h for mu-capture ELISA) . The red-cell IgM-antibody capture assay is therefore amenable to rapid diagnosis of M . pneumoniae infection and the institution of early appropriate antibiotic therapy. Int J Clin Pharmacol Ther Toxicol, 1988 Feb, 26(2), 84 - 7 Pharmacokinetics of netilmicin in renal insufficiency and hemodialysis; Herrero A et al.; The pharmacokinetics of netilmicin was studied in 26 patients with varying degrees of renal impairment (11 were dialysis patients) in order to determine the influence of kidney function status on the disposition of the antibiotic . The serum level curves of netilmicin follows a two-compartment open kinetic model . Several relationships between pharmacokinetic parameters and renal function indicators are defined . A clinical useful correlation indicates that the half-life is approximately 3 times the serum creatinine concentration, and may be used for adjusting the netilmicin dosage in the treatment of patients with impaired renal function . During hemodialysis the serum half-life decreases approximately 10-fold compared with the interdialysis periods . The percentage of dose extracted by hemodialysis during a single 4 h session is 56.1 +/- 6.65% . The dialysis clearance is 87.28 +/- 28.8 ml/min. Arch Biochem Biophys, 1988 Feb 1, 260(2), 601 - 8 Substrate specificity of nicotinamide methyltransferase isolated from porcine liver; Alston TA et al.; Nicotinamide methyltransferase (EC 2.1.1.1) has been purified over 1300-fold from porcine liver . The enzyme is electrophoretically homogeneous, exhibiting a relative molecular mass of 27,000 . In addition to acting on nicotinamide and close structural analogs such as thionicotinamide and 3-acetylpyridine, the enzyme actively accommodates poor analogs such as quinoline, isoquinoline, and 1,2,3,4-tetrahydroisoquinoline as methyl group acceptors . The enzyme may thus have the function of detoxicating numerous alkaloids in vivo . In some cases, the action of the enzyme might paradoxically increase the toxicities of substrates, but the hepatotoxic antibiotic pyrazinamide, which we considered as potentially such an enzyme-activated electrophile, did not function detectably as a substrate for the isolated enzyme. Klin Wochenschr, 1988 Feb 1, 66(3), 92 - 5 Histamine generation by bacteria in sputum of patients with chronic obstructive airway disease; Katgely B et al.; Previous investigations have demonstrated high histamine concentrations in the sputum of patients with chronic obstructive airway disease (COAD) . A possible histamine generation by bacteria has been discussed . In the present work, histamine concentrations in native and incubated sputum of patients with COAD were determined . Histamine was assayed fluorimetrically after separation by HPLC . Histamine concentration in native sputum amounted to 10-1140 ng/ml . After 72 h incubation at 37 degrees C 100-20,700 ng/ml histamine was detected . A mean 26-fold increase in histamine content was observed . Heating of the sputum almost completely prevented the rise in histamine concentration during incubation . The same effect was achieved by adding an antibiotic to the sputum before incubation . Histamine content in sputum of patients with COAD decreased considerably after therapy with the antibiotic doxycycline . Histamine formation by bacteria may account considerably for the histamine concentration in sputum of patients with COAD. Cancer Res, 1988 Feb 1, 48(3), 615 - 9 Effect of bleomycin on murine tumor cells at elevated temperatures and two different pH values; Urano M et al.; The cytotoxic effect of bleomycin, an antibiotic chemotherapeutic agent, at elevated temperatures was investigated . Single cell suspensions of FSa-II tumor cells were treated at elevated temperatures with or without bleomycin either at pH 7.4 or 6.7 . Immediately after treatment, cells were cooled and diluted for lung colony assay . Cyclophosphamide of 200 mg/kg was injected i.p . into the recipient mice 48 h before i.v . injection of tumor cells . Lungs were removed 13 days thereafter and fixed in Bouin's solution . Colonies formed on the surface of each lobe were counted, and the surviving fractions were calculated . Cell survival was determined as a function of treatment time at various temperatures . Survival curves following bleomycin treatment at various temperatures were biphasic . Initial steep portion was followed by a resistant tail . The surviving fractions were reduced to 0.1 within 20 min of treatment at pH 7.4 in the temperature range from 39.0 degrees-43.5 degrees C, and 10 min at pH 6.7 . The slope of the resistant tail becomes steeper with increasing temperature, indicating that the cytotoxic effect of bleomycin was enhanced at elevated temperatures . The reciprocal of D0 (treatment time to reduce surviving fraction from 1.0 to 0.37 on the exponential portion of survival curve) of the resistant tail was plotted as a function of the treatment temperature, and activation energy was calculated . This analysis indicates that the enhancement of the cytotoxic effect increases with increasing temperature . However, above 42.5 degrees C, this enhancement appears to be dominated by lethal thermal damage. Vet Rec, 1988 Jan 30, 122(5), 112 - 3 Treatment of cattle, sheep and horses with lincomycin: case studies; Plenderleith RW; In large animal practice, clinical cases involving deep-seated infections affecting bones, joints, meninges and the larynx are particularly difficult to treat . The antibiotic lincomycin has the ability to penetrate tissue of poor vascularity and is also effective in the presence of pus . Eleven cattle, six sheep and three horses were treated with the drug at various doses and in 75 per cent of the cases there was a positive response. Biochim Biophys Acta, 1988 Jan 22, 937(2), 387 - 97 Gramicidin S and dodecylamine induce leakage and fusion of membranes at micromolar concentrations; Eytan GD et al.; The effect of the antibiotic gramicidin S and the synthetic cationic amphipath dodecylamine on membranes was studied with large unilamellar vesicles containing phosphatidylcholine and varying concentrations of cardiolipin . Fusion of vesicles composed of equal amounts of the two phospholipids occurred with both drugs at concentrations lower than 10 microM . Fusion was accompanied by leakage of the contents, while higher drug concentrations caused complete loss of vesicle contents . Drug concentrations at least one order of magnitude lower were needed to induce leakage from vesicles containing only phosphatidylcholine . Under these conditions, contents leakage occurred with no measurable aggregation or membrane intermixing . On the other hand, much higher concentrations of both drugs were required to induce leakage from vesicles containing predominantly cardiolipin . Release of contents occurred upon aggregation of the vesicles and collapse of the vesicular organization, as well as formation of paracrystalline structure when dodecylamine was employed or amorphous material when gramicidin A was used . In contradistinction to other model systems, phosphatidylcholine was needed for fusion induced by the cationic amphipaths, and its presence reduced the threshold concentration of the drugs needed to induce leakage of the contents . The similar effects of the two drugs on membranes imply that, at least in these model membranes, the relevant feature of both drugs is only their amphiphatic nature. Biochim Biophys Acta, 1988 Jan 18, 968(1), 9 - 16 How does doxorubicin interfere with actin polymerization? Colombo R, Milzani A. It is well known that doxorubicin (adriamycin), an antibiotic with an antitumoral action, has some undesirable side effects . Among these, the most serious is, undoubtedly, damage to myocardial tissue (progressive cardiomyopathy) . We have for some time focused our attention on the effect of this drug on cellular contractile systems and, more specifically, on the process of actin polymerization, which we consider to be an extremely delicate key point for the economy of most cellular motor manifestations . In the present study, using capillary viscometry, spectrofluorometry and electron microscopy, we have shown a negative action of doxorubicin on various important chemical events which contribute to the transformation of G-actin into F-actin . Specifically, we found that the drug mainly acts by reducing the polymer size . A possible action mechanism of the antibiotic is proposed and a plausible correlation among the events described in vitro and those observed in vivo is advanced. Mol Biochem Parasitol, 1988 Jan 15, 27(2-3), 119 - 24 Depression of Plasmodium falciparum dihydroorotate dehydrogenase activity in in vitro culture by tetracycline; Prapunwattana P et al.; The activity of Plasmodium falciparum dihydroorotate dehydrogenase, a particulate, electron transport-linked enzyme involved in de novo pyrimidine synthesis, was depressed when the parasite was cultured in the presence of a therapeutic concentration of tetracycline over a 96 h period . There was no direct inhibitory effect of the antibiotic on the enzyme activity . The activity of glutamate dehydrogenase, which is cytoplasmic in the parasite, was unaffected by tetracycline over the same period . Dihydroorotate dehydrogenase activity was substantially recovered when electron acceptors were added . It is suggested that the effect of tetracycline is manifested at the level of the dehydrogenase and/or the electron transport chain linked to this enzyme. J Biol Chem, 1988 Jan 5, 263(1), 274 - 82 Isolation and characterization of Chinese hamster ovary cell mutants deficient in acyl-coenzyme A:cholesterol acyltransferase activity; Cadigan KM et al.; A protocol has been developed for isolating cholesterol ester-deficient cells from the Chinese hamster ovary cell clone 25-RA . This cell line previously was shown to be partially resistant to suppression of cholesterogenic enzyme activities by 25-hydroxycholesterol and to accumulate a large amount of intracellular cholesterol ester when grown in medium containing 10% fetal calf serum (Chang, T . Y., and Limanek, J . S . (1980) J . Biol . Chem . 255, 7787-7795) . The higher cholesterol ester content of 25-RA is due to an increase in the rate of cholesterol biosynthesis and low density lipoprotein receptor activity compared to wild-type Chinese hamster ovary cells, and not due to an abnormal acyl-CoA:cholesterol acyltransferase enzyme . The procedure to isolate cholesterol ester-deficient mutants utilizes amphotericin B, a polyene antibiotic known to bind to cholesterol and to form pore complexes in membranes . After incubation in cholesterol-free medium plus an inhibitor of endogenous cholesterol biosynthesis, 25-RA cells were found to be 50-500 times more sensitive to amphotericin B killing than were mutant cells containing reduced amounts of cholesterol ester . Twelve amphotericin B-resistant mutants were isolated which retained the 25-hydroxycholesterol-resistant phenotype . These mutants did not exhibit the perinuclear lipid droplets characteristic of 25-RA cells, and lipid analysis revealed a large (up to 40-fold) reduction in cellular cholesterol ester . The acyl-CoA:cholesterol acyltransferase activities of these cholesterol ester-deficient mutants were markedly lower than 25-RA when assayed in intact cells or in an in vitro reconstitution assay . The tightest mutant characterized, AC29, was found to have less than 1% of the parental acyl-CoA:cholesterol acyltransferase activity . These mutants all have reduced rates of sterol synthesis and lower low density lipoprotein receptor activity compared to 25-RA, probably as a consequence of their reduced enzyme activities . Cell fusion experiments revealed that the phenotypes of all the mutants examined are not dominant and that the mutants all belong to the same complementation group . We conclude that these mutants contain a lesion in the gene encoding acyl-CoA:cholesterol acyltransferase or in a gene encoding a factor needed for enzyme production. Med J Aust, 1988 Jan 4, 148(1), 47 - 9 Isolation of Acanthamoeba from a cerebral abscess; Harwood CR et al.; A 55-year-old diabetic aboriginal woman presented with a two-week history of fever, altered mental state and convulsions . On the basis of computed tomographic scanning a diagnosis of cerebral abscess was made . The pus that was drained produced no bacterial growth but, on microscopy, amoebic cysts were observed . Special cultures produced a growth of Acanthamoeba . The patient appeared to respond to drainage of the abscess and antiprotozoal therapy . Unfortunately, she developed necrotizing enteritis which led ultimately to her death . Antibiotic sensitivity and pathogenicity testing suggest that the Acanthamoeba were unusually virulent . The problems of diagnosis and management are discussed. Tierarztl Prax, 1988, 16(2), 139 - 41 {Small intestine obturation and perforation in a calf caused by a foreign body . Case report}; Doll K et al.; Obturation and perforation of the jejunum by an ingested fir branch was diagnosed in a 3 months old male German Fleckvieh calf . Following resection of the altered segment of intestine an end-to-end anastomosis was performed . The abdominal cavity was flushed with a 0.4% solution of polyvidon-iodine in normal saline, and an antibiotic preparation was instilled . Systemic antibiotic therapy was maintained for 6 days . Recovery was uneventful, and the animal was discharged 9 days after admission. Acta Anat (Basel), 1988, 132(3), 230 - 3 Effects of bacterial colonization on mucosal structure of the large bowel of neonatal rats; Hill RR et al.; Micro-anatomical changes in colonic and caecal epithelia of infant rats between birth and weaning appear to be the outcome of the effects of bacterial colonization, superimposed on the natural postnatal ontogeny of the mucous membranes . Conventional rat pups between 15 and 22 days of age showed development of subepithelial spaces in both caecum and colon, rupture of the overlying epithelium and loss of whole enterocyte plaques . Antibiotic-treated animals retained the large-bowel mucosal morphology of the 10-day-old rat, without any of the lesions described in conventional infants . Mucosal lesions were typical of ischaemic damage, possibly triggered by lumen anoxia during colonization. Acta Anat (Basel), 1988, 132(3), 205 - 15 Cholesterol-rich microdomains in rat and porcine thyroid membranes involved in TSH-induced endocytotic processes; Barriere H et al.; Filipin, a polyene antibiotic, was used to detect cholesterol in thyroid membranes in vivo and in culture during TSH stimulation . We found that apical and basolateral plasma membranes were heterogeneously modified by filipin which induced abundant lesions in apical membranes, whereas Golgi apparatus, endoplasmic reticulum, nuclear membranes were unmodified . Small apical vesicles and colloid droplets were generally highly enriched in these complexes, suggesting a high cholesterol concentration in their membranes . Pseudopod membranes, known to be highly specialized domains in the apical plasma membrane, appeared enriched in cholesterol . Consequently, we suggest that an increased cholesterol content may be involved in the stabilization of thyroid membranes during endocytotic processes. Cancer Chemother Pharmacol, 1988, 22(3), 197 - 200 The mechanism of action of quinocarmycin citrate (KW 2152) on mouse L1210 cells in vitro; Kanamaru R et al.; The effects of the antitumor antibiotic, quinocarmycin citrate (KW 2152), on L1210 cells were studied in vitro . The cellular growth was completely inhibited at 10(-6) M KW 2152, and after 2 days no viable cell was seen . The incorporation of 3H-thymidine, 3H-uridine, or 3H-leucine into the acid-insoluble fraction was not affected at 10(-4) M for 1 h; however, when the cells were treated with 10(-6) M for 24 h, the radioactivity appearing in the acid-insoluble fraction was reduced to 20%, 30%, and 48%, respectively, of the control . The single strand scission of the DNA of L1210 cells was seen at 10(-7) M for 24 h, as revealed by an alkaline, sucrose density gradient . However, no damage to plasmid pBR322 was observed even at 10(-6) M KW 2152 for 24 h, as revealed by 0.8% agarose gel electrophoresis, indicating that some soluble factors of the cells might contribute to the damage to the DNA of L1210 cells . The processing of pre-rRNA of the cells was not inhibited at 10(-6) M of the drug for 24 h of incubation. Chemotherapy, 1988, 34(2), 77 - 84 Enteral, oral, and rectal absorption of ceftriaxone using glyceride enhancers; Beskid G et al.; In vivo models in rodents and primates were used to investigate ways of overcoming the poor oral and rectal absorption of ceftriaxone . The sodium salt of ceftriaxone at 20 mg/kg was formulated in C8-C10 chain length, mono- and diglyceride extracts of coconut oil (Capmul) and administered intraduodenally to adult rats . Peak plasma levels of 17-52 micrograms/ml and bioavailability averaging 38% were attained . Significant plasma levels (42-45 micrograms/ml) were also demonstrated in squirrel monkeys with doses of 20 mg/kg ceftriaxone formulated in Capmul and given by the enteral route . Enteric-coated capsules containing this formulation were also orally administered to squirrel monkeys and gave high plasma levels (10-31 micrograms/ml) between 1 and 6 h following dosing . In rectal absorption studies, ceftriaxone formulated in Capmul as a suspension gave peak blood levels of 62-84 micrograms/ml (average bioavailability 42%) in the rabbit . In the baboon, rectal administration of ceftriaxone formulated with Capmul in a Witepsol H15 suppository gave Cmax levels ranging from 9 to 48 micrograms/ml, depending on the dose of the antibiotic and the drug/enhancer ratio. Poult Sci, 1988 Jan, 67(1), 145 - 8 Response of guinea fowl (Numida meleagris) to dietary supplementation of zinc bacitracin; Oguntona T et al.; The effect of dietary bacitracin on the growth and feed conversion of guineas has been investigated using graded levels of the antibiotic . The treatments were 0, 11, 22, and 45 mg bacitracin/kg diet . Poorest live weights were recorded by unmedicated guineas . Keets given bacitracin at 11 mg/kg recorded significantly higher live weights (P less than .05) than unmedicated chicks . Best live weights were obtained at a supplementation level of 22 mg/kg; supplementation to 45 mg/kg gave no further growth improvement. Zh Vopr Neirokhir Im N N Burdenko, 1988 Jan-Feb, (1), 27 - 30 {Comparative evaluation of surgical methods for treating brain abscesses}; Mosiichuk NM et al.; Data on the treatment of 69 patients with cerebral abscesses is discussed . Surgery was applied on 22 patients, the abscess was removed radically with the capsule . The best results were produced in removal of superficially located abscesses, in deep location the capsule was usually ruptured during its separation and severe inflammatory complications developed in the postoperative period and led to a fatal outcome in 50% of cases . The results were optimum when the seat of the abscess was drained by an inflow-outflow system and irrigated by antiseptic and antibiotic solutions, and also in treatment by the puncture method (31 patients). Food Addit Contam, 1988 Jan-Mar, 5(1), 77 - 83 Development of a method for the determination of oxytetracycline in trout; Murray J et al.; An HPLC method has been developed whereby oxytetracycline can be detected in trout muscle at 0.005 mg kg-1 . Application of the method to retail samples has shown that a few contained the antibiotic . The amounts found ranged from 0.008-0.037 mg kg-1, these concentrations being considerably below that specified under the Medicine Act review procedures. Can J Vet Res, 1988 Jan, 52(1), 5 - 11 Pharmacokinetics of tetracycline in the domestic rabbit following intravenous or oral administration; Percy DH et al.; Tetracycline hydrochloride was administered to domestic rabbits using a single bolus by the intravenous and oral routes . Pharmacokinetic parameters were determined for intravenous (10 mg/kg) and oral (150 mg/kg) administration . The effect of fasting for 12 h on the drug elimination kinetics after oral administration was evaluated . Tetracycline was added to the drinking water at 800 mg/L or 1600 mg/L . Drug and water intake and serum levels were monitored . Mean serum pharmacokinetic parameters following intravenous administration were; 0 intercept beta curve B (microgram/mL) = 7.5, rate of elimination from body -b (min-1) = 0.0058, half life elimination from body -t 1/2 b (min) = 120.0, wt(kg) = 3.2 determined using combined male and female data . Mean serum pharmacokinetic parameters after oral administration (single bolus) were -B (microgram/mL) = 1.54 (full stomach) and 2.71 (empty stomach), b(min-1) = 0.0037 (full stomach) and 0.0035 (empty stomach), t 1/2 b (min) = 190.3 (full stomach) and 216.2 (empty stomach) . Administration of tetracycline in the drinking water produced very low to nondetectable levels of drug in the serum, even at high dosage, and the 1600 mg/L drug concentration was accompanied by a significant drop in water intake . Thus, it is evident that concentrations of tetracycline of up to 1600 mg/L drinking water will not produce levels of antibiotic consistently detectable in the serum. J Pharm Sci, 1988 Jan, 77(1), 78 - 80 Determination of tetracycline hydrochloride in presence of anhydrotetracycline by differential pulse polarography; Sabharwal S et al.; A differential pulse polarographic method is described for the determination of the antibiotic tetracycline HCl in the presence of its degradation product anhydrotetracycline . The method utilizes the large difference in their differential pulse polarograms at a peak potential of -1.39 V in 0.1 M phosphate buffer as the base electrolyte (pH 6.8) . The assay was evaluated using synthetic mixtures and applied to the analysis of commercial tetracycline HCl samples . The results obtained with this method are in close agreement with those from the spectrophotometric absorbance ratio method. Neurosurgery, 1988 Jan, 22(1 Pt 1), 148 - 51 Subarachnoid hemorrhage and "normal pressure hydrocephalus": fatal complication of percutaneous microcompression of the gasserian ganglion . Case report; Spaziante R et al.; A 62-year-old man underwent percutaneous balloon catheter compression of the gasserian ganglion for typical trigeminal neuralgia . After this, a subarachnoid hemorrhage was discovered and normal pressure hydrocephalus developed, which required shunting . Although the neurological function recovered, the patient died 8 months later because of supervening hepatic insufficiency, probably caused by protracted antibiotic therapy . Such a fatal complication, the first one associated with the technique of percutaneous trigeminal compression, was perhaps predisposed by preexistent cerebral atrophy with enlargement of the subarachnoid spaces; the unforeseen piercing of the dilated trigeminal cistern probably permitted the intracranial subarachnoid diffusion of an otherwise trivial hemorrhage . The safety of the procedure may be greatly reduced in such instances. J Reprod Med, 1988 Jan, 33(1 Suppl), 164 - 7 Use of C-reactive protein to predict the outcome of medical management of tuboovarian abscesses; Mercer LJ et al.; Medical management of tuboovarian abscesses (TOAs) has been shown to be successful . However, the ability to predict which patients with TOA would respond to antibiotic therapy could shorten the hospital stay and decrease treatment costs . C-reactive protein (CRP), an acute-phase-reactant protein with a short half-life, was investigated as a possible predictor of response by TOA patients to medical therapy . Twenty-two patients with TOAs were admitted prospectively into this study, which included daily quantitative determinations of CRP . The patients had either resolution of the mass and symptoms (responders), increased evidence of systemic sepsis and acute peritonitis requiring surgery (failures) or continuation of the tender adnexal mass without evidence of peritoneal irritation (persisters) . Twelve patients classified as responders showed a continued daily decrease in quantitative CRP levels of at least 20% per day below the previous day's value until the return to normal levels . The five failures showed a progressive rise in CRP levels as well as evidence of systemic sepsis . Persisters showed an initial decrease in the CRP level followed by a leveling off of the value to a decrease of less than 20% per day . The rate at which daily CRP determinations decline may be a useful predictor of the response to antibiotic therapy. J Trauma, 1988 Jan, 28(1 Suppl), S159 - 62 Twenty-one-year experience with land mine injuries; Adams DB et al.; Land mines produce devastating injuries which are usually fatal . In Guantanamo Bay, there have been no survivors from close range, functioning antipersonnel mines of the M-16 series . All 15 antipersonnel mine fatalities suffered extremity amputation . Seven of the 15 patients suffered immediately fatal head, neck, or truncal injuries (Type I injury) . The three patients who underwent hospital resuscitation had extremity amputation but were spared major head, neck, or truncal injury . It is in this group of injured that potentially salvageable patients can be identified; for them aggressive rescue and resuscitation must be performed . Those with Type II injuries are the highest priority in any triage plan . In a mass casualty or combat casualty scenario, Type II patients, in particular those with high bilateral above-the-knee amputations, may be reassigned to an expectant treatment category so as to allow the main focus on more salvageable patients . The prehospital management plan emphasizes rapid assessment and triage of patients, use of tourniquets to control extremity hemorrhage, supplemental oxygen or endotracheal intubation if possible, neck immobilization, use of the extremity section of the pneumatic antishock garment if applicable, and rapid transport to a hospital . Hospital management of these patients emphasizes aggressive resuscitation, early endotracheal intubation, and rapid volume replacement with simultaneous balanced salt solution and blood . Operative debridement with broad-spectrum antibiotic coverage and tetanus prophylaxis is performed; wounds are managed in an open fashion and frequently examined at subsequent dates in the operating room. Crit Care Med, 1988 Jan, 16(1), 89 - 95 Surgical intervention in acute pancreatitis; Rattner DW et al.; There is no one operative treatment for acute pancreatitis . Surgery is indicated to resolve diagnostic uncertainty and perhaps to modify the early course of gallstone pancreatitis . Peritoneal lavage is useful in reversing early-phase systemic circulatory effects mediated by toxins in the ascitic fluid, but does not modify the underlying pancreatitis . When pancreatitis progresses to pancreatic and peripancreatic necrosis, the ultimate outcome is determined by a) the amount of necrosis, b) the extent of extrapancreatic necrosis, and c) bacterial contamination of necrosis . The amount of pancreatic regional necrosis that can be safely observed for healing is unknown; large collections tend to become infected secondarily and thus should be evacuated . Computed tomographic scanning is the best current means of detecting pancreatic necrosis and abscesses . Only percutaneous aspiration can reliably differentiate sterile from infected collections . As sepsis is the most common cause of death in acute pancreatitis, adequate surgical drainage is essential, while antibiotic therapy is only adjunctive . Aggressive treatment directed at the two principal causes of death, early-phase shock and late-phase sepsis, should reduce mortality to about 1% overall and to about 5% in cases complicated by regional necrosis and sepsis. Am J Obstet Gynecol, 1988 Jan, 158(1), 158 - 61 Absorbable synthetic mesh (polyglactin 910) for the formation of a pelvic "lid" after radical pelvic resection; Clarke-Pearson DL et al.; Isolation of the abdominal contents from the denuded, potentially infected pelvis after radical pelvic surgery has been advocated . Of the many materials evaluated, omentum is usually chosen . In six patients in whom omentum was unsuitable, we have substituted polyglactin 910 (Vicryl, Ethicon, Sommerville, New Jersey) mesh to form a pelvic "lid." In these patients, omentum was either densely adherent in the upper abdomen because of prior surgery or was removed as part of surgical treatment for recurrent cancer . Vicryl mesh formed a "lid" across the true pelvis . No gastrointestinal complications occurred in these patients . Four patients developed pelvic infections that resolved after surgical drainage and antibiotic therapy . No patients developed peritonitis above the pelvis . No chronic infections have been found in more than 12 to 48 months of follow-up . In this preliminary experience, Vicryl mesh appears to be useful for the formation of a pelvic "lid" after exenterative pelvic surgery when the omentum is unavailable. Mol Pharmacol, 1988 Jan, 33(1), 103 - 10 Selective inactivation of four rat liver microsomal androstenedione hydroxylases by chloramphenicol analogs; Stevens JC et al.; The steroid androstenedione has been shown to be a valuable tool for the study of the selective inactivation of cytochrome P-450 isozymes in intact rat liver microsomes . The validity of this approach was investigated using microsomes, purified cytochrome P-450 isozymes, antibodies to particular cytochromes P-450, and the known mechanism-based inactivator chloramphenicol . Enzyme inactivation and antibody inhibition studies show that microsomes from both phenobarbital- and non-phenobarbital-treated rats are needed to accurately monitor the inactivation of the major phenobarbital-inducible cytochrome P-450 isozyme (PB-B) and of the major constitutive androstenedione 16 alpha-hydroxylase (UT-A) . Similar experiments indicate that, although isozyme P-450g does catalyze the 6 beta-hydroxylation of androstenedione in a reconstituted system, this cytochrome appears to make only a minimal contribution to microsomal 6 beta-hydroxylase activity, which reflects instead the activity of pregnenolone-16 alpha-carbonitrile-induced isozymes . With these parameters investigated, initial enzyme inactivation studies showed that the antibiotic chloramphenicol caused different rates of NADPH-dependent enzyme inactivation among the four androstenedione hydroxylases monitored (16 beta greater than 6 beta greater than 16 alpha greater than 7 alpha) . Based on these data, 12 chloramphenicol analogs were examined, and the results with these compounds show that their selectivity as cytochrome P-450 inactivators is a function of at least three structural features: 1) the number of halogen atoms, 2) the presence of a para-nitro group on the phenyl ring, and 3) substitutions on the ethyl side chain . For example, the compound N-(2-phenethyl)dichloroacetamide was shown to reversibly inhibit but not inactivate the cytochrome(s) P-450 responsible for androstenedione 6 beta-hydroxylase activity, whereas N-(2-p-nitrophenethyl) and N-(1,2-diphenethyl)dichloroacetamide rapidly inactivated the 6 beta-hydroxylase . The ability to monitor the activity of multiple isozymes with a single substrate should allow the development of a systematic approach to the design of selective inactivators of rat liver cytochromes P-450. Clin Orthop, 1988 Jan, (226), 247 - 51 Management of civilian gunshot fractures of the extremities; Woloszyn JT et al.; One hundred thirty-two gunshot fractures of the extremities in 126 patients were studied retrospectively and followed until clinical union from January 1980 to January 1985 . Civilian handgun missile velocities have increased; should the trend continue, treatment protocols will need to be modified . All uncomplicated low-velocity gunshot fractures, less than 615 m/second, (2000 feet/second), can be managed conservatively, with superficial debridement, surgical cleansing, immobilization, and antibiotics . Seventeen orthopedic procedures were performed; specific treatment was dictated by the type or location of the fracture caused by the missile . One hundred thirty-two fractures were treated with antibiotic therapy, 80 intravenously and 52 oral administration . Only two infections were encountered, both in the oral therapy group . No statistically significant advantage of intravenous over oral administration was found . Emergency room debridement along with oral antibiotic therapy for uncomplicated low-velocity gunshot fractures not requiring operative fixation yielded results comparable to those of hospitalization, with dramatically reduced medical costs. Prog Clin Biol Res, 1988, 272, 351 - 9 Observations on the role of endotoxin in graft-versus-host disease; Lampert IA et al.; We have used a conventional murine model of bone marrow transplantation (BMT) to make a detailed study of the histological features of graft-versus-host disease (GvHD), and to study the effects of oral antibiotic decontamination of the gut flora . Comparison of the histological appearances of the small and large bowel indicated that the features of the GvHD were more severe in the large bowel . Bowel sterilisation caused a striking reduction in the severity of GvHD, both in the gut and at a distant site (the skin of the ear) . The different effects of GvHD in the large as compared to the small bowel suggested that a factor was operative locally, and the effect of sterilisation linked this to the bacteria in the bowel . The fact that sites remote from the bowel were also affected suggested that a diffusible factor from the bowel produced by the bacteria of the gut was responsible . Studies elsewhere have suggested that the factor involved is likely to be endotoxin . In these experiments however it was evident that systemic administration of endotoxin did not aggravate the disease process and that in some instances the reverse was obtained . If therefore endotoxin is important the dose and its mode of its administration are likely to be critical. Rev Pneumol Clin, 1988, 44(1), 43 - 7 {Reduction using an immunomodulator of the level of respiratory infections in chronic bronchitis}; Rochemaure J et al.; Fifty-six patients with recurrent bronchopulmonary infections associated with chronic bronchitis were randomly allocated to 2 groups, to assess whether treatment with an immunomodulator, Diribiotin CK, could enhance resistance to infection . The double-blind, placebo-controlled prospective trial over a 9 month period showed that this immunomodulator was well tolerated and significantly reduced the rate of respiratory tract infection . The drug also significantly reduced the prescribing of antibiotic medication and the rate of absenteism from work . These effects have been demonstrated in a rigorously designed clinical study . This is the first time that a clear clinical activity has been attributed to an inducer of soluble mediators of immunity. Prog Clin Biol Res, 1988, 264, 51 - 60 Design and conduct of clinical trials: development of a clinical study based on animal data; Hinshaw LB; There are numerous animal research studies documenting the effectiveness of corticosteroid and antibiotic therapy in E . coli-induced shock . Findings from other reports show equally effective treatment of shock induced by endotoxin, using corticosteroid without antibiotics . Early treatment using pharmacologic doses of corticosteroid is very effective in several species of animals in preventing or ameliorating the pathophysiologic changes induced by E . coli or endotoxin, and enhancing the probability of permanent survival (more than 7 days) . This form of treatment given acutely (first 12 hours) produces no observable detrimental effects in animal models . It was considered of extreme importance to determine if this particular therapy had successful human application . Results from previous clinical studies evaluating the effectiveness of corticosteroid in severe sepsis/septic shock were in marked conflict . We accepted the challenge to design a clinical study to determine if there were human subgroup populations with severe sepsis who responded similarly to the animal treated with corticosteroid. Can J Microbiol, 1988 Jan, 34(1), 30 - 7 In vitro stabilization of 6-methylsalicylic acid synthetase from Penicillium urticae; Lam KS et al.; In continuing studies of patulin biosynthesis, the first enzyme of the pathway, 6-methylsalicylic acid synthetase, was found to be far more labile than were the later enzymes of the pathway . Attempts were made to stabilize 6-methylsalicylic acid synthetase in vitro . The combined addition of the cofactor NADPH, the substrates acetyl-CoA and malonyl-CoA, the reducing agent dithiothreitol, and the proteinase inhibitor phenylmethylsulfonyl fluoride to cell-free extracts was found to prolong the half-life of the enzyme as much as 12-fold . This suggested that proteolysis and the conformational integrity of the enzyme may play an important role in controlling the duration of antibiotic biosynthesis in vivo . This was in agreement with the finding that the intracellular proteinase content of antibiotic-producing cells of Penicillium urticae rapidly increased just before the loss of 6-methylsalicylic acid synthetase content . These in vitro stabilization studies have provided some insight into the metabolic conditions that may stabilize these enzymes in vivo, and into possible ways of extending the life of these catalysts. Antibiot Khimioter, 1988 Jan, 33(1), 61 - 3 {Combined use of mytilan and gentamycin in experimental infections }; Krylova NV et al.; It was shown that mytilan, a polysaccharide isolated from the mantle of Crenomytilus grayanus stimulated the host nonspecific resistance to infections . This was evident from the survival rate of the animals infected with lethal doses of E . coli and S . aureus . In addition, the combined use of gentamicin and mytilan in treatment of the infections caused by the above organisms enabled to increase the antibiotic therapy efficacy with using lower doses of both the antibiotic and the polysaccharide. Zentralbl Chir, 1988, 113(4), 241 - 8 {Etiology and therapy of peritonitis in childhood}; Estel S et al.; The causes of peritonitis in childhood, particularly in infancy, were found to differ substantially from those in adult age . An overall account is given in this paper of general and differential diagnosis of extra-abdominal diseases which may be potentially mistaken for peritonitis . Clinical diagnosis is of crucial importance in childhood . Perforated appendicitis was the absolutely major cause of peritonitis in 119 children who received surgical treatment in the course of 18 years . An initial antibiotic combination of gentamicin with ampicillin, and metronidazole together with immune treatment have proved to be an effective therapeutic approach to this form of peritonitis. Kidney Int, 1988 Jan, 33(1), 29 - 35 Detection of endotoxin-like interleukin-1-inducing activity during in vitro dialysis; Lonnemann G et al.; In order to study the integrity of dialysis membranes to pyrogens, the dialysate side of a closed loop hemodialysis (HD) circuit was challenged with E . coli microfiltrate containing 500 ng/ml endotoxin . Three solutions, a) tissue culture medium/saline, b) 5% human serum albumin, and c) 10% fresh human plasma, were circulated in the blood loop for five hours . Samples drawn from the blood side were assayed for interleukin-1 (IL-1)-inducing activity on human mononuclear cells (MNC) in vitro . No IL-1-inducing substances were detected when saline or culture medium was circulated in the blood loop . Circulating 5% human serum albumin revealed IL-1-inducing activity in the samples drawn only after five hours of HD . However, the addition of 10% fresh human plasma to the blood side resulted in the appearance of an IL-1-inducing substance(s) after 15 minutes of HD . After 30 minutes, maximum IL-1-inducing activity was observed (control stimulation index, 3.30 +/- 0.67 SEM vs . 7.59 +/- 1.50, P less than 0.02) . The IL-1-inducing activity of the samples was completely inhibited by polymyxin B, a cationic antibiotic which blocks the IL-1-inducing activity of endotoxin . Additional experiments demonstrated that in vitro MNC IL-1-production induced by the same E . coli microfiltrate is enhanced in the presence of 10% plasma . These studies demonstrate that: (a) in the presence of plasma, IL-1-inducing factors pass into the blood compartment of a dialysis system challenged with bacterial pyrogen; and (b) MNC production of IL-1 is enhanced in the presence of plasma.(ABSTRACT TRUNCATED AT 250 WORDS) Chemotherapy, 1988, 34(1), 1 - 7 Penetration of cefuroxime and ceftazidime into human lungs; Perea EJ et al.; We have studied the penetration of cefuroxime and ceftazidime into lung tissue of 40 patients subjected to pulmonary surgery . Samples of blood and lung tissue were taken 1 and 2 h after antibiotic administration . Patients were randomly assigned to four dosage schedule groups: group A received a single intravenous injection of 750 mg cefuroxime; the lung tissue levels at 1 and 2 h were 9.6 +/- 3.1 and 4.54 +/- 2.64 micrograms/g of cefuroxime; the percentage penetration from serum into the lung tissue was 33.7 and 34.6%, respectively . Group B patients received three doses of 750 mg cefuroxime; lung tissue levels were 17.1 +/- 7.7 and 14.7 +/- 5.4 micrograms/g, the percentage of penetration being 89.1 and 102.8% at 1 and 2 h . Group C received a single intravenous injection of 1 g ceftazidime; the lung tissue levels were 16.3 +/- 10.1 and 10 +/- 5.04 micrograms/g; the percentage of penetration from serum was 38.3 and 35.3% . Group D received three doses of 1 g ceftazidime; the lung tissue concentrations were 11.98 +/- 7.5 and 8.5 +/- 7.3 micrograms/g and the percentage of penetration 35.1 and 32.2% at 1 and 2 h after last dose. Crit Rev Food Sci Nutr, 1988, 26(4), 359 - 95 The chemistry of lysozyme and its use as a food preservative and a pharmaceutical; Proctor VA et al.; The chemistry and use of lysozyme as a food preservative and a pharmaceutical are reviewed . Lysozyme inhibits the growth of deleterious organisms, thus prolonging shelf life . Chemicals used to improve the preservative effect of lysozyme and those that inhibit the enzyme are discussed, along with the stability of lysozyme in various chemical environments . Lysozyme has been used to preserve fresh fruits and vegetables, tofu bean curd, seafoods, meats and sausages, potato salad, cooked burdock with soy sauce, and varieties of semihard cheeses such as Edam, Gouda, and some Italian cheeses . Lysozyme added to infant-feeding formulas makes them more closely resemble human milk . Lysozyme has been used clinically in the treatment of periodontitis, administered in chewing gum, and implemented to prevent tooth decay . It has also been administered to patients suffering from cancer for its analgesic effect and has been used as a potentiating agent in antibiotic therapy. Arch Neurol, 1988 Jan, 45(1), 99 - 104 Lyme disease and its neurologic complications; Finkel MF; Lyme disease is recognized as a cause of illness involving multiple organ systems . The transmission of the Borrelia burgdorferi spirochete depends on a complicated vector life cycle, involving multiple mammalian and avian hosts . Although the illness is reported worldwide, variable clinical presentations on different continents raise questions about disease mechanisms . Multiple neurologic syndromes can occur alone or in combination, producing peripheral neuropathies, radiculopathies, myelopathies, encephalitides, meningitides, and pain syndromes . These may be noted with dermatological, rheumatological, and cardiological syndromes . Several pathophysiologic mechanisms are reviewed . Antibiotic therapy for different clinical presentations is discussed. Arch Surg, 1988 Jan, 123(1), 106 - 9 Ultrasonic guided percutaneous transhepatic bile drainage for cholangitis due to intrahepatic stones; Huang MH et al.; Acute cholangitis due to intrahepatic stones is frequently associated with biliary sepsis . Emergency surgery for these high-risk patients is usually associated with a high mortality . Therefore, we recommend nonoperative methods for the management of this acute disease . Percutaneous transhepatic cholangiography and drainage (PTCD) combined with antibiotic and fluid treatment was used successfully in the management of 41 patients with acute pyogenic cholangitis due to intrahepatic stones . The general condition of th