Biochem Biophys Res Commun, 1990 Jul 31, 170(2), 426 - 32 Acivicin: a highly active potential chemotherapeutic agent against visceral leishmaniasis; Mukherjee T et al.; Acivicin, a chlorinated amino acid antibiotic, is found to be remarkably effective in killing both the vector and the host form of the parasitic protozoa, Leishmania donovani, the causative agent for visceral leishmaniasis or Kala-azar . The ED50 (50 nM) for the pathogenic amastigote form in in vitro screening system is significantly lower than the reported values for other drugs under trial . The drug irreversibly inactivates both in vitro and in vivo carbamyl phosphate synthetase II, the first enzyme of the pyrimidine biosynthetic pathway . The irreversible inactivation of this sensitive target enzyme and lack of effective reversal by glutamine makes acivicin a preferred candidate for potential chemotherapy against increasing number of Kala-azar cases that are reported to be unresponsive to pentavalent antimonials. N Engl J Med, 1990 Jul 26, 323(4), 219 - 23 Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles; Steere AC et al.; BACKGROUND AND METHODS . A small percentage of patients infected with Borrelia burgdorferi have chronic Lyme arthritis that does not respond to antibiotic therapy . To learn whether genetically determined variations in the host immune response might account for such outcomes, we determined the immunogenetic profiles of 130 patients with various manifestations of Lyme disease . RESULTS . Of the 80 patients with arthritis, 57 percent of those with chronic arthritis (12 to 48 months in duration) had the HLA-DR4 specificity; only 23 percent of those with arthritis of moderate duration (6 to 11 months) and only 9 percent of those with arthritis of short duration (1 to 5 months) had this specificity (P = 0.003) . After the HLA-DR4-positive patients were excluded from each group, a secondary association was noted with HLA-DR2, which was found in 75 percent of the remaining patients with chronic arthritis and in 50 percent of those with arthritis of moderate duration, but in only 20 percent of those with arthritis of short duration (P = 0.023) . Altogether, 25 of the 28 patients with chronic arthritis (89 percent) had HLA-DR2 or HLA-DR4, or both, as compared with 27 percent of those with arthritis of short duration (relative risk, 22; P = 0.00006) . These HLA specificities appeared to act as independent, dominant markers of susceptibility . Nucleotide-sequence typing, performed in five patients with chronic arthritis, identified the HLA-DR2 allele as Dw2 (DR beta 1*1501), and the HLA-DR4 alleles as Dw4, Dw14, and Dw13 (DR beta 1*0401, DR beta 1*0404, and DR beta 1*0403, respectively) . The presence of HLA-DR4 in patients with arthritis was associated with a lack of response to antibiotic therapy (P = 0.01) . CONCLUSIONS . Particular Class II major histocompatibility genes determine a host immune response to B . burgdorferi that results in chronic arthritis and lack of response to antibiotic therapy. Biochem Biophys Res Commun, 1990 Jul 16, 170(1), 209 - 13 Recombinant gene expression in human umbilical vein endothelial cells transduced by retroviral vectors; Zwiebel JA et al.; Endothelial cells are attractive targets for gene transfer because of their immediate contact with the bloodstream, and, therefore, they might serve as vehicles for therapeutic drug delivery . Recently, we and others reported that endothelial cells of animal origin efficiently express both secretory and nonsecretory recombinant proteins . We now show that human endothelial cells are also capable of expressing a recombinant gene following transduction with retroviral vectors . Human umbilical vein endothelial cells were transduced with either the N2 or the SAX vector . Following selection with G418, cells transduced by both vectors were found to express neophosphotransferase activity, the product of the neomycin resistance gene . The fact that a recombinant gene can be readily inserted and efficiently expressed into human endothelial cells suggests that these cells may be able to serve a role in human gene therapy. Nucleic Acids Res, 1990 Jul 11, 18(13), 3731 - 7 Molecular modelling study of changes induced by netropsin binding to nucleosome core particles; Perez JJ et al.; It is well known that certain sequence-dependent modulators in structure appear to determine the rotational positioning of DNA on the nucleosome core particle . That preference is rather weak and could be modified by some ligands as netropsin, a minor-groove binding antibiotic . We have undertaken a molecular modelling approach to calculate the relative energy of interaction between a DNA molecule and the protein core particle . The histones particle is considered as a distribution of positive charges on the protein surface that interacts with the DNA molecule . The molecular electrostatic potentials for the DNA, simulated as a discontinuous cylinder, were calculated using the values for all the base pairs . Computing these parameters, we calculated the relative energy of interaction and the more stable rotational setting of DNA . The binding of four molecules of netropsin to this model showed that a new minimum of energy is obtained when the DNA turns toward the protein surface by about 180 degrees, so a new energetically favoured structure appears where netropsin binding sites are located facing toward the histones surface . The effect of netropsin could be explained in terms of an induced change in the phasing of DNA on the core particle . The induced rotation is considered to optimize non-bonded contacts between the netropsin molecules and the DNA backbone. Biochim Biophys Acta, 1990 Jul 9, 1026(1), 93 - 8 Kinetic study of interaction between {14C}amphotericin B derivatives and human erythrocytes: relationship between binding and induced K+ leak; Wietzerbin J et al.; The relationship between polyene antibiotic binding to red cells and their membrane permeabilization was studied using two 14C-labelled amphotericin B (AmB) derivatives: N-fructosyl AmB and N-acetyl methyl ester AmB . The binding kinetics of both derivatives were determined on whole red cells and ghosts . The resulting experimental points were well fitted by monoexponential functions, and the characteristic t1/2 for both derivatives were calculated from these functions . At 2 X 10(-5) M, the half time t1/2 for N-acetyl methyl ester AmB (30.2 min) which forms aqueous aggregates was longer than the t1/2 for the more soluble species N-fructosyl AmB (4.5 min) . At lower concentrations (10(-7) M), the t1/2 for N-acetyl methyl ester AmB (6.3 min) in a more solubilized form was close to that of N-fructosyl AmB (7.9 min) . These results suggest that only solubilized species bound to red cell membranes and that disaggregation of aggregates is the limiting step in the binding process . The permeabilization of red cell membranes by N-fructosyl AmB, measured as intracellular K+ leak, was not instantaneous and at 10 degrees C external K+ was only detected 20 min after antibiotic addition . In contrast, binding occurs without lag time . Consequently, different mecanisms underlie binding and K+ permeability inducement . Absorption spectroscopy data showed that bound antibiotic is located in the hydrophobic membrane interior and that this penetration of the membrane by AmB derivatives occurs without lag time . Consequently, the lag time occurring for K+ permeability inducement would be due to some steps subsequent to binding and probably located in the hydrophobic membrane interior . This statement is further supported by the observation that the lag time is sensitive to changes in membrane fluidity as shown here by the break between 20 and 30 degrees C in the slope of the Arrhenius plot for the lag time, coinciding with the phase transition in red cell membranes. Biopolymers, 1990 Jul-Aug 5, 29(8-9), 1297 - 306 Conformational studies of nikkomycin X in aqueous solution; Krainer E et al.; Nikkomycin X is a peptidyl-nucleoside antibiotic that inhibits chitin synthesis in fungi . Information on its conformation in aqueous solution was obtained from pH titration studies in which the nmr shifts of exchangeable and nonexchangeable protons were monitored . These studies and nuclear Overhauser effects support an unfolded or conformationally flexible structure for the antibiotic, and the syn and anti conformations of the nucleoside moiety were found to coexist . The conformation of the ribose ring was determined using a two-state model; a slight shift from type N to type S conformers occurred as the pH was raised from 1 to 6. Biochemistry, 1990 Jul 3, 29(26), 6145 - 53 Preferential binding of daunomycin to 5'ATCG and 5'ATGC sequences revealed by footprinting titration experiments; Chaires JB et al.; Results from a high-resolution deoxyribonuclease I (DNase I) footprinting titration procedure are described that identify preferred daunomycin binding sites within the 160 bp tyr T DNA fragment . We have obtained single-bond resolution at 65 of the 160 potential binding sites within the tyr T fragment and have examined the effect of 0-3.0 microM total daunomycin concentration on the susceptibility of these sites toward digestion by DNase I . Four types of behavior are observed: (i) protection from DNase I cleavage; (ii) protection, but only after reaching a critical total daunomycin concentration; (iii) enhanced cleavage; (iv) no effect of added drug . Ten sites were identified as the most strongly protected on the basis of the magnitude of the reduction of their digestion product band areas in the presence of daunomycin . These were identified as the preferred daunomycin binding sites . Seven of these 10 sites are found at the end of the triplet sequences 5'ATGC and 5'ATCG, where the notation AT indicates that either A or T may occupy the position . The remaining three strongly protected sites are found at the ends of the triplet sequence 5'ATCAT . Of the preferred daunomycin binding sites we identify in this study, the sequence 5'ATCG is consistent with the specificity predicted by the theoretical studies of Chen et al . {Chen, K.-X., Gresh, N., & Pullman, B . (1985) J . Biomol . Struct . Dyn . 3, 445-466} and is the very sequence to which daunomycin is observed to be bound in two recent X-ray crystallographic studies . Solution studies, theoretical studies, and crystallographic studies have thus converged to provide a consistent and coherent picture of the sequence preference of this important anticancer antibiotic. Klin Padiatr, 1990 Jul-Aug, 202(4), 275 - 7 {Effect of 7S immunoglobulin substitution on the incidence and course of infection in cytostatic drug treated patients}; Hadjilaskari P et al.; This retrospective analysis evaluates the effect of intravenously administered immunoglobulin against infections occurring during bone marrow depression after cancer chemotherapy in 85 children with leukemia and lymphoma . There was no statistical difference between patients with and without immunoglobulin administration neither when immunoglobulins were used prophylactically nor therapeutically in addition to antibodies during episodes of infection . Duration of fever, duration of antibiotic therapy, maximum of temperature, white blood cell counts, and kind of infections were comparable in 84 fever episodes in patients who had received immunoglobulin therapeutically and 69 fever episodes in patients who had not . This study supports the aspect that immunoglobulin administration does not have preventive or therapeutic efficacy on infections during cancer chemotherapy in children. Dev Med Child Neurol, 1990 Jul, 32(7), 639 - 42 Adverse effects of trimethoprim-sulfamethoxazole in a child with dihydropteridine reductase deficiency; Woody RC et al.; A child with dihydropteridine reductase (DHPR) deficiency developed signs of dopamine insufficiency after being given trimethoprim-sulfamethoxazole (TMP-SMX) . She recovered function after the antibiotic was stopped, which suggests that it adversely influenced dopamine metabolism in the CNS . The authors speculate that TMP, a dihydrofolate reductase inhibitor, was the major cause of the patient's deterioration, and suggest that it and other dihydrofolate inhibitors, notably methotrexate, are contra-indicated for patients with DHPR deficiency. J Antibiot (Tokyo), 1990 Jul, 43(7), 788 - 95 Structures of cepafungins I, II and III; Terui Y et al.; Structures of interesting acylpeptide antibiotics cepafungins I, II and III were elucidated by NMR spectroscopic studies and some degradation experiments . The antibiotics contain a common peptide part that consists of threonine and two unusual amino acid residues, gamma-hydroxylysine and 4-amino-2-pentenoic acid . The unusual amino acid residues compose an interesting 12-membered ring with an exocyclic N-terminus to which the threonine is connected . Different fatty acyl groups connected to the N-terminus of the threonine distinguish the three cepafungins . The major component I and minor component III are new substance, but the minor component II has a structure identical with that of the recently reported antibiotic glidobactin A. Antimicrob Agents Chemother, 1990 Jul, 34(7), 1360 - 5 Comparative toxicities of amphotericin B and its monomethyl ester derivative on glial cells in culture; Racis SP et al.; Amphotericin B (AmB) is a potent antifungal polyene macrolide antibiotic and is the drug of choice for the treatment of deep-seated mycotic infections . Its use is limited, owing to its nephrotoxicity, and it must be dispersed in deoxycholate for parenteral administration . In contrast, AME (the monomethyl derivative of AmB) is water dispersible, is appreciably less cytotoxic than AmB toward a variety of cell types, and is reportedly active against the acquired immunodeficiency syndrome virus (human immunodeficiency virus type 1) . The latter activity has generated interest in AME as an antiviral drug . However, AME is perceived to be neurotoxic, based on the outcome of a human clinical trial of AME as an antifungal drug . AmB is not regarded as neurotoxic, presumably because any neurotoxicity in vivo is precluded by its nephrotoxicity . It was important, therefore, to determine the potential for neurotoxicity of the two agents in comparative tests, assessing the effects of their direct action against neural cells in culture . Rat cortical cells, comprising astrocytes and oligodendrocytes, were used . AME was at least 10 times less toxic than AmB and equally less toxic against several other nonneural cell types also included in these tests . Equally important, AmB disrupted the myelin sheath in these cultures, and it inhibited its generation . AME did not, even at a concentration 10 times greater than the toxic concentration of AmB . AmB is, therefore, potentially more neurotoxic than AME, contrary to current perception . AME is effective as an antifungal and antiviral drug at a concentration far below its toxic concentration for neural cells . Also, AME does not cross the blood-brain barrier appreciably, so that a therapeutic level in blood can be expected without encountering neurotoxicity. Am Surg, 1990 Jul, 56(7), 407 - 11 The effects of chemotherapy on murine wound healing and orocutaneous fistula closure; Whittle T et al.; The effects of cisplatin and 5-fluorouracil on wound breaking strength and the rate of closure of an orocutaneous fistula were studied in 80 male rodents . Treatment rats received a total of 4.6 mg/kg cisplatin and 62 mg/kg 5-fluorouracil in six doses/12 days; control rats received 0.9 per cent saline . After treatment, 30 treatment and 30 control rats received a dorsal skin incision which was closed primarily . Wound breaking strength were tested at one, three and five weeks in ten rats from each group . An 8-mm orocutaneous fistula was made in the remaining ten treatment and ten control rats; the rate of closure was noted weekly . Cisplatin and 5-fluorouracil did not significantly impair wound breaking strength at one, three, or five weeks . The rate of closure of the orocutaneous fistula was not effected by cisplatin/5-fluorouracil . The chemotherapy caused severe facial cellulitis and death in four orocutaneous fistula rats . Combined chemotherapy with cisplatin and 5-fluorouracil should not interfere with planned surgical care of head and neck tumors . Concomitant antibiotic coverage, however, is advocated. Infect Immun, 1990 Jul, 58(7), 2289 - 96 Biological evaluation of Mycoplasma pulmonis temperature-sensitive mutants for use as possible rodent vaccines; Lai WC et al.; Temperature-sensitive mutants (TSMs) of Mycoplasma pulmonis were produced by treating the wild-type strain with N-methyl-N'-nitro-N-nitrosoguanidine . Three TSMs were selected at 38 degrees C, as a restrictive temperature, and at 34 degrees C, as a permissive temperature . Two TSMs, UTCMI and UTCMII, were proven to be nonpathogenic but immunogenic . In addition, they did not induce pneumonia, tracheitis, or tympanitis but did induce mild rhinitis . They were stable after 10 passages in vitro and in vivo . They elicited excellent antibody production and cell-mediated immunity in vaccinated rats . They also were not mitogenic to rat lymphocytes . Rats immunized intranasally with these TSMs were significantly protected against challenge with wild-type organisms . These mutants were morphologically and serologically indistinguishable from the wild-type organisms . The growth characteristics and antibiotic sensitivities were similar to those of wild-type organisms, except that they grew only at 34 degrees C . In contrast to wild-type organisms, they did not bind to or lyse sheep erythrocytes . Thus, these TSMs may qualify as a vaccine to prevent M . pulmonis infection in rats. Antibiot Khimioter, 1990 Jul, 35(7), 5 - 8 {Method for developing a controlled process . Study of the possible regulation of rifamycin B biosynthesis}; Kuz'mina LM et al.; A procedure for developing a controlled process for biosynthesis of secondary metabolites is described with reference to rifamycin B as an example . The response of the antibiotic producing culture to changed concentrations of the main nutrients in the initial medium was determined . Mathematical processing of the experimental findings with design of the experiment resulted in defining nutrients such as ammonium sulfate and cornsteep liquor useful for further development of the controlled process. Antibiot Khimioter, 1990 Jul, 35(7), 38 - 40 {Hypotension caused by intravenous infusion of rifampicin and its relation to the administration schedule}; Berezhinskaia VV et al.; It was shown in studies on animals that bolus administration of rifampicin induced hypotension whose severity depended on the rate of the antibiotic administration . When the antibiotic was administered in the 5-, 10- or 15-minute regimen in a dose of 10 mg/kg the maximum decrease in blood pressure was 44, 34 or 21% of the initial level and the maximum antibiotic concentration attained in the blood was 34.4, 27.2 or 22.6 micrograms/ml, respectively . With the infusion for 30 minutes, the maximum antibiotic concentration in the blood was 17.6 micrograms/ml and the blood pressure did not undergo any significant changes . When the rate of the antibiotic infusion was high there was pharmacokinetic heterogeneity of the blood serum and biophase which could lead to unpredictable results . After repeated administrations of rifampicin to the same animals pronounced tachyphylaxis to the antibiotic was noted, which manifested itself in decreasing of hypotension, though the serum antibiotic level was 1.5 to 2 times higher that the initial one . It was concluded that administration of rifampicin in the therapeutic dose equal to 10 mg/kg for 30 minutes was the most sparing regimen for the antibiotic bolus intravenous infusion . Gradual increase in the antibiotic dose and administration rate in patients is possible under careful control of blood pressure and pharmacokinetic studies. Antibiot Khimioter, 1990 Jul, 35(7), 3 - 5 {Effect of protoplast formation and regeneration on the production of nebramycin complex in Streptomyces cremeus subsp . tobramycini}; Malanicheva IA et al.; Production of the nebramycin complex in Streptomyces cremeus subsp . tobramycini before and after the protoplast formation and regeneration was comparatively studied . The antibiotic production was estimated by the total activity and component composition of the nebramycin complex . It was found that formation and regeneration of the protoplast led to lowering of the activity and changing of the complex component composition . Strains mainly synthesizing each one of the three basic components of the nebramycin complex were isolated . The strains proved to be unstable by the antibiotic production property and after three subcultures lost the differences in the complex component composition. Antibiot Khimioter, 1990 Jul, 35(7), 12 - 3 {Structure of the chromophore fragment of copsomycin}; Alekseeva LE et al.; The chromophore moiety of the copsomycin molecule was isolated in the form of dimethyl ether as an individual substance from the products of antibiotic acid hydrolysis . Physicochemical properties of the chromophore were studied . UV, 1H and 13C NMR, mass spectrometry and elementary analysis showed that the copsomycin molecule moiety was identical to the chromophore moiety of the molecule of multiomycin or nosiheptide. Cancer Biochem Biophys, 1990 Jul, 11(3), 217 - 26 Metal ions modulate the effect of doxorubicin on actin assembly; Colombo R et al.; Doxorubicin (DXR) exhibits a significant activity in many human malignant neoplasms but, unfortunately, produces many undesirable cellular troubles which mainly lead to a severe dose-dependent cardiomyopathy . Many Authors had suggested that doxorubicin interacts with actin and affects the intracellular ion composition; following this reasoning, we studied the effect of doxorubicin on actin polymerization in vitro induced by different metal ions . In this paper we show that the negative action of doxorubicin on actin polymerization (inhibition of filament growth, reduction of polymer amount and polymer size at steady-state) is strongly ion-dependent . With this finding, we suggest that the direct action of antibiotic on actin assembly, in the presence of the drug-related changes in cytoplasmic electrolyte pattern, could become predominant in vivo. Arkh Anat Gistol Embriol, 1990 Jul, 99(7), 32 - 9 {Morphofunctional changes in the lymph nodes and microcirculatory bed of small-intestinal mesentery of dogs in septic peritonitis after endolymphatic administration of ampicillin}; Shcherbakova EG et al.; With the aim to study effectiveness+ of endolymphatic (EL) administration of ampicillin (AC), using the model of an acute diffuse septic peritonitis in dogs, the morphological and morphometrical investigation has been performed concerning the state of the lymph nodes (LN), which are regional as regards the pathological focus (pelvic) and remote (tracheobronchial, mesenteric) and hemomicrocirculatory bed (HMCB) of the small intestine mesentery . All LN groups studied are involved in the pathological process, that produces certain increasing disturbances in the structure and cell composition in LN . In 6 h the changes are especially manifested in the pelvic LN, and in 18 h--in the animals without application of AC, or at its intramuscular injection LN lose their typical structure . Their dimensions and number of lymphoid nodules++ and medullary cords decrease, a sharp impoverishment of lymphocytes in LN is observed . By this time critical disturbances in the HMCB structure develop; they are characterized as presence of great amount of avascular areas in the mesentery, extended capillary loops, plasmatic saturation of interstitium . When AC is injected endolymphatically, simultaneously with peritonitis modelling T- and B-dependent zones in LN are preserved, a high volumetric part of lymphocytes is kept in all groups of LN, structure and function of HMCB are normalized . The pronounced delay in development and decreasing manifestation of infective-toxic disorder in LN and HMCB depend on effective concentrations of the antibiotic, produces in the lymphatic system. Arch Pharm (Weinheim), 1990 Jul, 323(7), 383 - 5 Synthesis and pharmacological studies of some (1,4)-naphthoquinono{3,2-c}-1H-pyrazoles, 2-substituted amino-1,4-naphthoquinones, and related compounds; Tandon VK et al.; Series of (1,4)-Naphthoquinono(3,2-c)-1H-pyrazoles and 2-substituted amino-1,4-naphthoquinones have been synthesised and studied for their possible anticancer activity (animal tumours, Walker 256 carcinosarcoma), Influenza RNA transcriptase activity, antibiotic activity (C . neoformans, T . mentagraphytes, M . canis, A . niger, and C . albicans). Vestn Otorinolaringol, 1990 Jul-Aug, (4), 31 - 2 {Effect of the functional state of the eustachian tube on the sanative process after ear surgery}; Iagudin KF; After radical operation 40 patients, who showed exacerbation of chronic purulent otitis media, were treated for problems of the Eustachian tube . All the patients showed granular salpingitis . The patients were subdivided into two groups with respect to the therapeutic method used: 1) in 18 patients, a punctured bougie-catheter was inserted into the Eustachian tube . The catheter was used to wash the tube with antiseptics (dioxydin, balyse-2, microcide) and to blow oxygen for 20 min; 2) in 22 patients, the permeability of the Eustachian tube was restored by bougieurage; then an antibiotic ointment was administered and, after purulent discharge stopped, solcoseryl ointment was placed . It was concluded that the incidence of exacerbations of chronic purulent otitis media after radical operation decreased, when the Eustachian tube underwent specific therapy. Biol Chem Hoppe Seyler, 1990 Jul, 371(7), 567 - 73 Brefeldin A prevents uncovering but not phosphorylation of the recognition marker in cathepsin D; Radons J et al.; Brefeldin A (BFA) has been shown to inhibit transiently the subcellular transport of cathepsin D (Oda & Nishimura (1989) Biochem . Biophys . Res . Commun . 163, 220-225) . We studied the effect of this antibiotic on processing of the phosphorylated oligosaccharides in cathepsin D in human promonocytes U937 . In the presence of the drug the phosphorylation of cathepsin D precursor continued at a diminished rate . The phosphorylated oligosaccharides in cathepsin D comprised mono- and bis-phosphorylated forms . The relative amounts of the two species were not changed in the presence of BFA . The uncovering of the phosphate groups and the proteolytic processing of the phosphorylated precursor were abolished . In an in vitro assay the uncovering enzyme, N-acetylglucosamine-1-phosphodiester N-acetylglucosaminidase was not inhibited by BFA . We suggest that this drug interrupts the traffic between the compartments containing N-acetylglucosaminyl phosphotransferase and N-acetylglucosamine-1-phosphodiester N-acetylglucosaminidase. Somat Cell Mol Genet, 1990 Jul, 16(4), 369 - 82 Antisense RNA inhibition of HPRT synthesis; Stout JT et al.; The abundant production of antisense hypoxanthine phosphoribosyltransferase (HPRT) RNA in NIH-3T3, COS, or HeLa cells leads to an inhibition of HPRT synthesis . HPRT enzyme levels in cells transfected with mouse HPRT antisense RNA expression vectors are reduced to less than 1% of parental cell activity, resulting in resistance to 6-thioguanine (6TG) . The expression of antisense HPRT RNA leads to a marked reduction in the steady-state levels of endogenous HPRT mRNA . Furthermore, we demonstrate that intron-specific antisense RNA, complementary to sequences adjacent to splice donor or acceptor sites of the first intron of the mouse HPRT gene, are effective in depressing endogenous HPRT levels . These studies suggest that antisense RNA can inhibit gene expression in the nucleus, possibly by perturbing nuclear RNA processing. J Antimicrob Chemother, 1990 Jul, 26(1), 81 - 6 The penetration of ceftriaxone into human brain tissue; Lucht F et al.; The cerebral penetration of ceftriaxone in patients who underwent surgery for cerebral tumours was investigated . Seventeen patients received 2 g of ceftriaxone given intravenously 2 to 13 h before blood and brain samples were taken . Antibiotic levels were determined by an agar-well diffusion method . Cerebral ceftriaxone concentrations ranged from 0.3 to 12 micrograms/g, with a mean value of 1.63 micrograms/g . These values were less than 2% of corresponding serum concentrations, but enough to inhibit 75% of bacterial strains recently isolated from brain abscesses in our unit. Cesk Farm, 1990 Jul, 39(5), 220 - 2 {Interaction of tobramycin and its derivatives with mitochondria in vitro}; Kusnir J et al.; Tobramycin modified with fluorescamin yields fluorescent derivatives with a gradually changed structure and charge composition . Interactions of these drugs with mitochondria were investigated on the basis of the measurement of their inhibitory effect on the respiration (consumption of O2) of the isolated mitochondria . The results were compared with the effects of the original antibiotic agent . The use of the method of fluorescence polarization made it possible to determine the character of interactions . The procedure is a model experiment with possible wider use. Pediatr Nephrol, 1990 Jul, 4(4), 445 - 50 Immediate and long-term renal effects of fetal exposure to gentamicin; Gilbert T et al.; Aminoglycoside antibiotics, like gentamicin, given to pregnant females cross the placenta and accumulate in the fetal kidney, which, like the adult kidney, was found to be the major site of deposition . In young guinea-pigs whose mothers were given gentamicin during the week following nephrogenesis in the fetus, nephron growth was found to be retarded temporarily . In rats whose mothers were given gentamicin during the period of fetal nephrogenesis, the final number of nephrons was reduced by about 20% . In both cases, renal development was impaired, although the concentration of gentamicin in the fetal kidney was lower than that measured in the kidney of human fetuses whose mothers had received a single injection of aminoglycoside . In rats exposed to gentamicin in utero, cellular damage of the undifferentiated and differentiating renal tissues was observed . It is, there are likely that the oligonephronia observed in animals born of gentamicin-treated mothers resulted from a direct effect of the drug at early stages of nephrogenesis . When gentamicin administration to the mother was prolonged, part of the oligonephronia observed at birth might have also resulted from fetal growth retardation, secondary to adverse effects of the drug on the mother . Providing it was not associated with fetal growth retardation, the presence of high gentamicin concentrations in the fetal kidney at late stages of nephrogenesis did not affect nephron differentiation . Long-term studies of rats born with gentamicin-induced oligonephronia showed that neither the antibiotic still present in kidney several weeks after birth, nor the injuries it caused, prevented renal growth and morphological adaptation of the nephrons to their reduced number.(ABSTRACT TRUNCATED AT 250 WORDS) Int J Clin Pharmacol Ther Toxicol, 1990 Jul, 28(7), 286 - 91 Temocillin: lymph penetration and protein binding; Staniforth DH et al.; Temocillin, a novel betalactam antibiotic, was administered in doses of 1,2 and 4 g i.v . to 12 healthy subjects and the plasma concentrations of free and protein bound temocillin assayed and protein binding parameters were calculated . In a second study 2 g of temocillin was administered i.v . to 12 healthy subjects and samples of lymph were collected and assayed for total temocillin . Using the protein binding parameters so obtained the corresponding free temocillin in lymph was calculated . The clinical significance of the lymph penetration is discussed. World J Surg, 1990 Jul-Aug, 14(4), 513 - 6; discussion 516-7 Splenic abscess; Alonso Cohen MA et al.; We present 7 cases of splenic abscess collected in our hospital from 1980 to 1988 as well as a review of 227 cases of the world literature . The signs and symptoms are nonspecific in all of them, fever being the most constant . Computed tomography scan followed by sonography were demonstrated to be the best methods of diagnosis . The treatment carried out on all of our patients was splenectomy followed by antibiotic coverage . Two of them died 15 days after the operation due to persistence of the septic state . In our review of the literature, we observe a rise in the population at risk for splenic abscess due to an increase in the use of immunosuppressive agents, to the higher survival of leukemic patients, and to the great incidence of drug abuse among others . Nevertheless, the advances in the use of sonography and computed tomography scan have made possible a more accurate diagnosis, therefore making possible an earlier treatment and a better prognosis . We believe that the treatment of choice is splenectomy with conservative treatment used only in specific cases where surgery represents a high risk for the patient. J Clin Microbiol, 1990 Jul, 28(7), 1580 - 5 Accuracy of Chlamydia trachomatis antigen detection methods in a low-prevalence population in a primary care setting; Gann PH et al.; We compared a direct fluorescent-antibody stain (DFA) and an enzyme immunoassay (EIA) with a standard cell culture technique for the detection of Chlamydia trachomatis infection in women in an urban family practice setting . We also evaluated a DFA sample in a commercial laboratory to determine the interlaboratory reliability of this test . There were 268 women in the study; the EIA provided a higher sensitivity (83 versus 50%) and a higher positive predictive value (83 versus 69%) than the DFA test and comparably high specificity (99 versus 98%) . Concordance between the two laboratories on the DFA test was not high when data were adjusted for chance agreement (kappa coefficient = 0.64) . DFA validity was optimal with an elementary body cutoff of greater than 5, while EIA validity was optimal at the recommended cutoff of 0.1 optical density unit . None of 11 women with negative cultures after treatment had false-positive antigen tests . False-negative results with both tests were associated with low culture inclusion counts but were not strongly associated with the presence or absence of symptoms, menses, pregnancy, or recent antibiotic use . False-positive results with EIA were seen only for three women who had a chief complaint of vaginal discharge . Although the positive predictive value of DFA could be increased in high-prevalence subpopulations, EIA was still more valid in two such groups: teenagers and prenatal patients . These results indicate that EIA might be preferable for low- or moderate-prevalence populations in primary care settings and that a falloff in DFA sensitivity could be explained by lower infection burdens in low-prevalence groups. Am Fam Physician, 1990 Jul, 42(1), 102 - 12 New trends in the management of peritonsillar abscess; Epperly TD et al.; Peritonsillar abscess is the most common complication of acute tonsillitis . Signs and symptoms include fever, unilateral sore throat, odynophagia and trismus . Optimal management consists of antibiotic therapy and drainage of the abscess . Controversy exists about the drainage procedure, which includes needle aspiration, incision and drainage, or acute tonsillectomy . Data indicate that outpatient needle aspiration, antibiotics and pain medication are effective treatment in 85 to 90 percent of patients with uncomplicated peritonsillar abscesses. J Bacteriol, 1990 Jul, 172(7), 3790 - 8 Cloning of spiramycin biosynthetic genes and their use in constructing Streptomyces ambofaciens mutants defective in spiramycin biosynthesis; Richardson MA et al.; Several cosmid clones from Streptomyces ambofaciens containing the spiramycin resistance gene srmB were introduced into S . fradiae PM73, a mutant defective in tylosin synthesis, resulting in tylosin synthesis . The DNA responsible for this complementation was localized to a 10.5-kilobase EcoRI fragment . A 32-kilobase DNA segment which included the srmB spiramycin resistance gene and DNA which complemented the defect in strain PM73 were mutagenized in vivo with Tn10 carrying the gene for Nmr (which is expressed in Streptomyces spp.) or in vitro by insertional mutagenesis with a drug resistance gene (Nmr) cassette . When these mutagenized DNA segments were crossed into the S . ambofaciens chromosome, three mutant classes blocked in spiramycin synthesis were obtained . One mutant accumulated two precursors of spiramycin, platenolide I and platenolide II . Two mutants, when cofermented with the platenolide-accumulating mutant, produced spiramycin . Tylactone supplementation of these two mutants resulted in the synthesis of a group of compounds exhibiting antibiotic activity . Two other mutants failed to coferment with any of the other mutants or to respond to tylactone supplementation. J Neurosurg, 1990 Jul, 73(1), 98 - 105 Response of malignant glioma cell lines to activation and inhibition of protein kinase C-mediated pathways; Pollack IF et al.; To evaluate the role of protein kinase C-mediated pathways in the proliferation of malignant gliomas, this study examined the effect of a protein kinase C (PKC)-activating phorbol ester (12-O-tetradecanoyl-13-phorbol acetate or TPA) and a protein kinase C inhibitor (polymyxin B) on deoxyribonucleic acid (DNA) synthesis of malignant glioma cells in vitro . A serum-free chemically defined medium, MCDB 105, was employed for all studies . Two established human malignant glioma cell lines (T98G and U138), two rat glioma lines (9L and C6), and two low-passage human glioma lines (obtained from surgical specimens) were studied . With the exception of the C6 line, all tumors responded in a dose-dependent fashion to nanomolar concentrations of TPA with a median effective dose that varied from 0.5 ng/ml for the U138 glioma to 1 ng/ml for the T98G glioma . At optimal concentrations (5 to 10 ng/ml), TPA produced a two- to five-fold increase in the rate of DNA synthesis (p less than 0.05) as assessed by incorporation of 3H-thymidine . However, TPA had no additive effect on the mitogenic response produced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) . Inhibition of PKC using the antibiotic polymyxin B (20 micrograms/ml) abolished the TPA-induced mitogenic response in the five responsive lines tested . In two tumors (U138 and 9L), polymyxin B also eliminated EGF-, PDGF-, and serum-induced DNA synthesis as well as abolishing baseline DNA synthesis . These cells remained viable, however, as assessed by trypan blue exclusion; after removal of polymyxin B from the medium, they were able to resume DNA synthesis in response to TPA and serum . In the three other tumors (T98G and the two low-passage human glioma lines), growth factor-induced and serum-induced DNA synthesis were inhibited by approximately 25% to 85% . It is concluded that PKC-mediated pathways affect DNA synthesis in the human malignant glial tumors studied . The response of the glioma cells to TPA is similar to the responses seen in fetal astrocytes, but differs significantly from those reported for normal adult glial cultures . Because the response of the 9L glioma to TPA is similar to the responses seen in the human tumors, the 9L rat glioma model may prove useful for examining the role of PKC-mediated pathways in controlling glioma growth in vivo. J Allergy Clin Immunol, 1990 Jul, 86(1), 4 - 10 Variable expression of IgG2 deficiency; Kavanaugh AF et al.; Sustained and significant reversal of antibody deficiencies is uncommon, although it has been noted in some cases during childhood and after viral infections . We report a case of reversal of IgG2 deficiency after splenectomy . A 46-year-old man who suffered recurrent sinusitis despite antibiotic therapy was noted to have IgG2 deficiency and cutaneous anergy . Replacement therapy with intravenous immunoglobulin ameliorated his symptoms . After 13 months of therapy, the patient had a diagnostic laparotomy and splenectomy because of portal hypertension, hypersplenism, and consideration of underlying malignancy . No evidence of malignancy or infection, including human immunodeficiency virus, active cytomegalovirus, or Epstein-Barr virus infection, was found . After splenectomy, the patient's serum IgG2 level normalized without replacement therapy . Subsequently, it fell, then normalized once more, and remains normal . The patient also demonstrated positive reactions to delayed hypersensitivity testing after splenectomy, but, subsequently, became anergic and remains anergic at the present time . Since the splenectomy he has remained clinically well without antibiotics or immunoglobulin replacement . In vitro analysis of his lymphocyte function demonstrated impaired T cell proliferation as well as an intrinsic B cell differentiation defect . This case demonstrates the potentially dynamic nature of IgG subclass deficiencies. Cancer Res, 1990 Jul 1, 50(13), 3897 - 904 Role of natural killer cells and macrophages in the nonspecific resistance to tumors in mice stimulated with SMANCS, a polymer-conjugated derivative of neocarzinostatin; Suzuki F et al.; Copoly(styrene-maleic acid)-conjugated neocarzinostatin (SMANCS), a lipophilic derivative of the proteinaceous antitumor antibiotic neocarzinostatin, has been reported to stimulate a nonspecific resistance to tumors (NSRT) in solid tumor-bearing mice, in addition to its chemotherapeutic antitumor effect through the arrest of DNA synthesis by direct DNA strand scission . In the present study, splenic or peritoneal effector cells were used to investigate the ability of SMANCS to augment natural killer (NK) cell activity and to generate cytostatic macrophages (A-M phi) . Splenic NK cell activity augmented by SMANCS was characterized by cytotoxicity to various target cells, nylon wool nonadherence, and sensitivity to treatment with anti-asialo-GM1 antiserum or monoclonal anti-Thy-1.2 antibody followed by complement . The A-M phi generated by SMANCS stimulation were characterized by their adherence to a plastic surface coated with fetal calf serum and their ability to phagocytize carbonyl-iron . The maximum level of NK cell activity in the spleens of mice was detected 3 days after i.v . injection of SMANCS, and the highest activity of the peritoneal A-M phi was demonstrated in mice 4 days after SMANCS treatment . On the other hand, the NSRT of mice stimulated with SMANCS was not detectable in mice treated with carrageenan or trypan blue, whereas SMANCS-stimulated NSRT was observed in mice treated with anti-asialo-GM1 antiserum . The NSRT that was stimulated with SMANCS was also demonstrated in mice homozygous for the beige mutation and their non-beige littermates, when NK cell-resistant EL-4 thymoma was used as a tumor target . These results suggest that the expression of NSRT of mice stimulated with SMANCS may require the function of A-M phi, although NK cell activity was also augmented in spleens of mice by administration of SMANCS. Rev Med Chil, 1990 Jul, 118(7), 796 - 804 {Reactive arthritis . A review}; Gutierrez F et al.; The arthritides that meet the definition or reactive arthritis include the so-called seronegative spondyloarthropathies . Patients are usually aged less than thirty-two . Preceding infection is generally intestinal or venereal, although the involved agent may remain unknown . Enteric forms occur in small epidemics, whereas venereal forms correlate with a recent new sexual partner . The clinical picture varies in severity, with manifestations overlapping between disorders, and often the first complaint is extra-articular . Highly suggestive of reactive arthritis is "sausage" deformity of fingers and toes, pain and stiffness about multiple joints accompanied by radiating lower back discomfort, and enthesitis, particularly at the Achilles tendon . One out of six or seven patients becomes disabled; therapy aimed at preventing disability is vital since medication has little effect on spinal involvement . Antibiotic therapy may be effective in cases in which specific etiologic agents are well defined. Mutat Res, 1990 Jul, 236(1), 43 - 50 DNA breaks and repair in the mouse leukemia L1210 cells exposed to three different types of interstrand DNA cross-linkers; Yajima N et al.; DNA breaks and repair in mouse leukemia L1210 cells treated with 3 different types of cross-linkers, mitomycin C (MMC), 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride (ACNU) and SN-07 (a macromolecular antibiotic), were studied . Measured in D37 values, MMC gave the highest number of cross-links per lethal 'hit' directly after the 1-h treatment in the alkaline elution assay, followed by ACNU and SN-07 . A good dose-response increase in induced interstrand DNA cross-linking frequency was observed in cells treated with 2.5-10 micrograms/ml MMC and with 10-100 micrograms/ml ACNU for 1 h with and without 24-h post-incubation . After 6-h post-incubation, the highest frequency of cross-linking was observed in cells treated with 2.5 micrograms/ml MMC and 30 micrograms/ml ACNU, while cross-link production continued in the cells treated with SN-07 for 12-h post-incubation . No significant increase in DNA breaks was observed in cells treated with MMC throughout 24-h post-incubation . The highest frequency of single-strand DNA breaks in cells treated with ACNU was observed immediately after the treatment and they disappeared after 6-h post-incubation . After 24-h post-incubation, a marked enhancement of the DNA breaks was observed in cells treated with SN-07 and the cells contained double-strand DNA breaks also . RNA synthesis was not affected in the cells treated with 10 micrograms/ml MMC and slightly inhibited to 70% of control in those treated with 100 micrograms/ml ACNU, while DNA synthesis in both cells was significantly inhibited after 24-h post-incubation . By contrast, both RNA and DNA synthesis were completely inhibited in cells treated with 8.0 micrograms/ml SN-07. Clin Podiatr Med Surg, 1990 Jul, 7(3), 501 - 8 Bite wound infections of the lower extremity; Myers RA et al.; Animal bite wounds of the lower extremity are considered high-risk wounds for infection, especially in the medically compromised individual . Management should be aggressive . Copious irrigation and debridement of the wound clearly proves to be of greater value in the prevention of infection than the indiscriminate use of so-called "prophylactic" antibiotic agents . Frankly infected wounds must also be managed aggressively, incorporating the use of antibiotics to eradicate the infection . Empiric use of an agent containing clavulanic acid or sulbactam is suggested until results are obtained from the bacterial culture and sensitivity . Tetanus prophylaxis should be considered for every bite wound, whereas rabies prophylaxis is warranted in selected cases. Immunopharmacology, 1990 Jul-Aug, 20(1), 57 - 61 Effect of FK-506 and cyclosporine on human T and B lymphoproliferative responses; Wasik M et al.; The macrolide antibiotic FK-506 causes a strong inhibition of human T and B cell proliferation in vitro in concentrations 100-fold lower than cyclosporine (CsA) . However, B cell activation appears to be less sensitive to the immunosuppressive action of FK-506 than T cell responses . There was no indication of a synergistic interaction of the two agents . In contrast, CsA added together with FK could counteract the immunosuppressive activity of the latter drug. Br J Haematol, 1990 Jul, 75(3), 340 - 5 MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia; Sato H et al.; The expression of the MDR1 gene was studied by Northern blot analysis in leukaemic cell specimens obtained from 74 patients with acute myelogenous leukaemia (AML) . No relationship was found between MDR1 RNA levels and FAB type of leukaemia or patient age . Transcript levels tended to be highest in the leukaemic cells of patients with a history of toxic exposure or preleukaemia compared with 'standard risk' patients at diagnosis but the differences were not significant (P = 0.07) . Patients whose leukaemic cells contained high MDR1 transcript levels were difficult to induce into remission and, if remission was induced, the remissions were short . Hence high levels of MDR1 expression may explain, at least in part, the ineffectiveness of anthracycline antibiotic containing treatment regimens in some patients with AML. Wien Med Wochenschr, 1990 Jun 30, 140(12), 311 - 4 {Mycoplasmas and arthritis}; Hulsemann JL et al.; Since 1898 Mycoplasmas are known triggers of different diseases in various animal species . In man they can cause among others non-gonococcal urethritis . In addition they are discussed as triggering agents of arthritis . Besides septic arthritides in immunocompromised patients with hypogammaglobulinemia, they might be causative agents in sexually acquired reactive arthritis, as in Reiter's syndrome . Various diagnostic tests are available . Antibiotic therapy is derived from experience with urogenital infections, proved investigations are pending. Biochem Biophys Res Commun, 1990 Jun 29, 169(3), 1211 - 6 Evidence for one-electron oxidation of benzylpenicillin G by lactoperoxidase compounds I and II; Metodiewa D et al.; The ability of the widely used antibiotic benzylpenicillin G to undergo a peroxidatic oxidation to produce free radical species has been investigated using conventional spectrophotometry, rapid scan spectrophotometry and an ESR spin trapping technique . Lactoperoxidase was used as a model for a drug oxidizing system . The results of the investigation indicate a normal peroxidatic pathway of benzylpenicillin degradation which leads to superoxide radical generation. J Natl Cancer Inst, 1990 Jun 20, 82(12), 1042 - 6 Excess of seminomas observed in Vietnam service U.S . military working dogs; Hayes HM et al.; During the Vietnam War, US military working dogs served with their companion dog handlers in close proximity, sharing common exposures to war-related activity, many zoonotic infectious agents, chemical pesticides, phenoxy herbicides, and extensive use of therapeutic drugs . To gain insight into the effects of the Vietnam experience, we investigated the occurrence of neoplasms in military working dogs based on standard necropsy examination by the Armed Forces Institute of Pathology . We observed that these dogs experienced significant elevated risks for testicular seminoma and, independently, testicular dysfunction . Experimental evidence shows testicular dysfunction and impaired spermatogenesis in laboratory animals exposed to phenoxy herbicides, dioxin, or tetracycline, and antibiotic used extensively in military working dogs in Vietnam . Because an unexplained significant decrease in sperm quality in Vietnam veterans has been observed by the Centers for Disease Control, further research is warranted if we are to clarify military service in Vietnam as a risk factor for testicular dysfunction . The testis should be made a priority site in the study of Vietnam experience-related cancers. Pol Tyg Lek, 1990 Jun 18-25, 45(25-26), 517 - 9 {Gentamicin level in the prostate and its pharmacokinetics in patients with benign prostatic hypertrophy}; Dyderski S et al.; The study involved 15 male patients with periurethral prostatic adenoma without complete anuresis . The patients were given 80 mg of gentamicin intramuscularly one day before surgery and 80 mg in a one-hour infusion immediately before an operation . Gentamicin blood concentrations were measured . Pharmacokinetic parameters were calculated and dosage schemes for each patient basing on the antibiotic blood levels . Gentamicin levels in removed adenomas were also determined . Adenomas weighed between 18.0 and 45.8 grams while gentamicin concentration ranged from 1.31 to 3.8 micrograms/mL . It was found that gentamicin concentration in adenomas depend upon their weight . Moreover, pharmacokinetic parameters of this antibiotic exert negligible effect on its levels in adenoma. Clin Ter, 1990 Jun 15, 133(5), 323 - 7 {Therapy of bacterial pharyngo-tonsillitis in children with piperacillin-flucloxacillin combination}; Romano A et al.; The authors evaluated the activity and safety of piperacillin/flucloxacillin in 40 children suffering from bacterial pharyngo-tonsillitis . The combination proved to be effective with regard to this pathology and no toxic or allergic side-effects were reported . This confirms the wide spectrum of the antibiotic. Rev Prat, 1990 Jun 11, 40(17), 1575 - 80 {Lung transplantation and cystic fibrosis}; Chazalette JP; It is only in 1983-84 that lung transplantation has been contemplated in cystic fibrosis patients . The French programme, reported here, began in 1987 . The criteria of inclusion are detailed, including antibiotic dependence, oxygen dependence, poor spirometric profile, destabilized nutritional status and very low Shwachman's score . The hepatic, cardiac, pulmonary, gastrointestinal, endocrine and psychological situations leading to temporary or definitive exclusion are defined . Once this evaluation has been made, the patients to be put on the waiting list are chosen collegially . The principles of medical and surgical treatment are exposed: immunodepressants and anti-infectious agents are prescribed to get over the immediate postoperative period (rejection and infectious complications) and to prevent the constitution of the much feared bronchiolitis obliterans; the indications of surgical techniques (HLT and BPT) should be more accurate . Among the 100-150 cases of lung transplantation recorded in the world, 30 were performed in France . We can safely say that 70 p . 100 of these patients are still alive and 40 p . 100 are in a remarkably good condition . This overall view is both exciting and disappointing, considering the results obtained and the ever-increasing waiting lists (more than 100 cases in France); hence the need for improving the present programme side by side with genetic and therapeutic studies which will eventually make surgery unnecessary. Biochim Biophys Acta, 1990 Jun 11, 1025(1), 109 - 15 A novel method for the efficient entrapment of calcium in large unilamellar phospholipid vesicles; Veiro JA et al.; A technique for the efficient entrapment of high concentrations of Ca2+ in large unilamellar phospholipid vesicles (LUVs), using the carboxylic acid antibiotic ionophore A23187 (calcimycin) is demonstrated . It is shown that rapid A23187-mediated entrapment of Ca2+, corresponding to essentially 100% sequestration of the extravesicular cation may be achieved for egg yolk phosphatidylcholine LUVs (100 nm) in the presence of a transmembrane proton gradient (acidic interior) . Interior-exterior concentration cation gradients of over 400-fold may be readily achieved, with interior Ca2+ concentrations in excess of 250 mM . It is shown that the extent and efficiency of the A23187-mediated uptake process is affected by the intravesicular buffering capacity and the extravesicular Ca2+ concentration in a manner that is consistent with a Ca2(+)-H+ exchange process . In the absence of a pH gradient, or the presence of a reversed gradient (basic interior), only background levels of cation uptake are detected . The driving force for A23187-mediated uptake of Ca2+ is shown to depend on the intravesicular proton pool rather than on a chelation process . This protocol provides a novel method for the efficient entrapment of high concentrations of Ca2+ and other cations in phospholipid vesicles. Fortschr Med, 1990 Jun 10, 108(17), 338 - 40 {Raw food and immunity}; Gaisbauer M et al.; Uncooked food is an integral component of human nutrition, and is a necessary precondition for an intact immune system . Its therapeutic effect is complex, and a variety of influences of raw food and its constituents on the immune system have been documented . Such effects include antibiotic, antiallergic, tumor-protective, immunomodulatory, and anti-inflammatory actions . In view of this, uncooked food can be seen as a useful adjunct to drugs in the treatment of allergic, rheumatic and infectious diseases. Vet Rec, 1990 Jun 9, 126(23), 567 - 70 Peritonitis in adult horses: a review of 21 cases; Mair TS et al.; The clinical signs in 21 adult horses affected by peritonitis (unassociated with gastrointestinal rupture or surgical interference of the abdomen) included colic (18 cases), pyrexia (15 cases), weight loss (six cases) and diarrhoea (five cases) . The diagnosis was based on a nucleated cell count in peritoneal fluid greater than 10(10)/litre . Haematological abnormalities (either neutropenia or neutrophilia) were present in 17 animals, and hyperfibrinogenaemia was identified in 14 . Twelve of the 21 horses survived after intensive antibiotic therapy; the other nine were destroyed either at exploratory laparotomy or after continued clinical deterioration . Necrosis or perforation of the bowel wall was found post mortem in eight of the horses. Farmaco, 1990 Jun, 45(6 Suppl), 757 - 69 A rapid evaluation of tetracycline and its dehydration products by UV derivative spectrophotometry; Vetuschi C et al.; This paper described a rapid ultraviolet spectrophotometric assay for simultaneous determination of tetracyclines (TC + ETC) and their anhydroderivatives (ATC + EATC), by using third- or fourth-derivative spectra recorded on samples in ethanol or dioxane . The analytical procedures are based on linear relationships between specific peak-trough values and the relative concentrations of tetracycline and of ATC-EATC, in mixtures containing TC, ATC and EATC . The toxic EATC can be estimated about half of the anhydrotetracyclines concentration values . The determination limit of anhydroderivatives is 0.05% . A simple purity test of the antibiotic is also reported . Accuracy, precision and linearity are discussed . The method is particularly applicable to routine analysis of products containing TC, in bulk and in some pharmaceutical formulations. J R Coll Surg Edinb, 1990 Jun, 35(3), 169 - 71 Bowel preparation or not for elective colorectal surgery; Duthie GS et al.; The importance of bowel preparation in elective colorectal surgery has often been stressed . We have surveyed the current practice of bowel preparation and chemoprophylaxis amongst surgeons in Wales and the south-west of England . From this we identified one surgeon who used no preoperative preparation and his results are reported in detail . One hundred consecutive colorectal cases were studied from one surgeon (J.M.P-T.) . There was a 7% incidence of wound infection and one anastomosis leaked . None of these patients had mechanical bowel preparation but all had antibiotic chemoprophylaxis . Mechanical bowel preparation is usual in the UK . These results demonstrate that its importance as a factor in wound infection and anastomotic dehiscence may be overstated. Antimicrob Agents Chemother, 1990 Jun, 34(6), 1268 - 70 Influence of temperature on degradation kinetics of ceftriaxone in diluted and undiluted human serum; Esteban MJ et al.; The stability of ceftriaxone in undiluted human serum and in human serum diluted 1/20 in 0.1 M phosphate buffer (pH 6.0) was measured at -70, -40, -20, 4, and 37 degrees C . Ceftriaxone in diluted human serum contained at least 90% of the initial activity after 3 months of storage at -20, -40, and -70 degrees C; unbuffered human serum contained 82.41, 84.92, and 88.96% of the initial activity, respectively . Ceftriaxone in unbuffered human serum and in diluted human serum showed 80.33 and 86.25% of the initial activity, respectively, after 55 days at 4 degrees C . After 120 h at 37 degrees C, this antibiotic in unbuffered human serum contained 33.08% of the initial activity, whereas samples of diluted human serum contained more than 60% . Consequently, the stability of antibiotic in human serum diluted 1/20 in 0.1 M phosphate buffer (pH 6.0) is increased. Pathol Biol (Paris), 1990 Jun, 38(5 ( Pt 2)), 495 - 9 {Biliary elimination and hepatic disposition of piperacillin: experimental evaluation}; Brogard JM et al.; The rate of biliary elimination and the hepatic disposition of piperacillin were studied by using an experimental model of a three hours perfusion of five isolated rabbit liver preparations . After addition of 10 mg of the antibiotic to the circulating blood, a mean biliary peak of 1,013 +/- 305 micrograms/ml was obtained between the 30th and 60th minute . The cumulated biliary elimination (0-3 hr) amounted to 5,665 +/- 389 micrograms (56.7% of the dose given) . The hepatobiliary clearance was calculated to 134.2 ml/hr and the biliary elimination rate constant to 0.5 545 (h-1) . After the procedure, 7.2 +/- 2.7% of the dose of piperacillin was still present in the circulating blood and 0.4 +/- 0.1% in the liver . The degradation of the antibiotic in the perfusion device concerned 24.9% of the dose . The percentage of piperacillin undergoing hepatic biotransformation, calculated by subtraction, was 10.8% . Under these conditions, the biliary elimination of piperacillin is much higher than that of the twenty other beta-lactams studied in our laboratory by the same experimental procedure. Ophthalmic Surg, 1990 Jun, 21(6), 407 - 11; discussion 411-2 Molteno rip-cord suture hypopyon; Ball SF et al.; Seven of 27 eyes developed hypopyons following removal of a 4-0 chromic suture that had been placed intraoperatively in the lumen of the tube of a Molteno implant as a temporary occlusion device . The hypopyons were sterile to anterior chamber tap and in six of seven cases resolved with only routine antibiotic coverage . Surgeons contemplating using an internal chromic suture occlusion in Molteno implants, however, should be aware of this potential problem and adopt a conservative, noninvasive approach. J Laryngol Otol, 1990 Jun, 104(6), 482 - 4 Bilateral choanal atresia: key to success with the transnasal approach; Singh B; The intranasal approach is generally accepted as the route of choice in the correction of bilateral choanal atresia but unfortunately it is associated with a significant incidence of stenosis . Over a five-year period, we have diagnosed bilateral choanal atresia in 30 neonates . Trans-nasal surgery was performed on 27 of them . All belonged to the Black race group . The incidence was 1:8,300 live births . There was a female predominance of 5:1 . Four (13 per cent) had other associated anomalies . One was a twin . Various factors were analysed to determine the cause of the stenosis . These were: 1 . Drilling compared with curettage of the bony atretic plate . 2 . Stenting versus non-stenting . 3 . Soft versus hard Portex tube stenting . 4 . Variation of stenting period--six, eight and twelve weeks . 5 . The use of prophylactic broad spectrum antibiotic for the whole of the stenting period . The conclusion derived from this study is that curettage of bony atresia, stenting with soft Portex tube for a period of six weeks and the use of broad spectrum antibiotic for the entire stenting period eliminates the problem of stenosis associated with the trans-nasal approach for the correction of bilateral choanal atresia. Am J Obstet Gynecol, 1990 Jun, 162(6), 1412 - 9; discussion 1419-20 Shirodkar cerclage in a multifactorial approach to the patient with advanced cervical changes; Novy MJ et al.; Patients with a markedly effaced or dilated cervix and protruding membranes between 21 and 26 weeks' gestation were managed by Shirodkar cervical cerclage, perioperative tocolysis, broad-spectrum antibiotic therapy, and, in selected cases, inhibition of prostaglandin synthesis with indomethacin . The average duration of pregnancy after cerclage in nine patients was 11.8 weeks (range, 1 to 18 weeks) . The mean birth weight was 2456 gm (range, 810 to 4341 gm) . Eight of the nine pregnancies resulted in live infants (fetal survival rate, 89%); six patients (66%) were delivered at or near term . Preterm delivery occurred at 28 and 35 weeks' gestation in two patients and premature rupture of the membranes occurred in another at 25 weeks, 5 days after cerclage . There was no maternal postoperative or postpartum morbidity . A multifactorial approach to the patient with advanced cervical changes and protruding membranes in the second trimester resulted in a high rate of fetal survival and prolongation of pregnancy until term in the majority of patients . The Shirodkar cerclage holds a distensible cervix closed while the adjunctive medical therapy restores homeostasis. J Thorac Cardiovasc Surg, 1990 Jun, 99(6), 958 - 66; discussion 966-8 Postpneumonectomy empyema . The role of intrathoracic muscle transposition; Pairolero PC et al.; Forty-five patients (36 male and nine female) were treated for postpneumonectomy empyema . All were initially managed with the first stage of the Clagett procedure (open pleural drainage) . In 28 patients with associated bronchopleural fistula the fistula was closed and reinforced with muscle transposition at the time of open drainage . Seven patients had multiple flaps . The serratus anterior muscle was transposed in 28 patients, latissimus dorsi in 11, pectoralis major in four, pectoralis minor in one, and rectus abdominis in one patient . After the fistula was closed and the pleural cavity was clean, the second stage of the Clagett procedure (obliteration of the pleural cavity with antibiotic solution and closure of the open pleural window) was done . The number of operative procedures ranged from 1 to 19 (median 5.0) . Length of hospitalization ranged from 4 to 137 days (median 34.0 days) . There were six operative deaths (mortality rate 13.3%), none in the patients who had both stages of the Clagett procedure . Follow-up of the 39 operative survivors ranged from 2.1 to 90.2 months (median 21.8 months) . Eighty-four percent of patients in whom the Clagett procedure was completed (26/31) had a healed chest wall with no evidence of recurrent infection . The bronchopleural fistula remained closed in 85.7% of patients (24/28) . There were 19 late deaths, none related to postpneumonectomy empyema . We conclude that the Clagett procedure remains safe and effective in the management of postpneumonectomy empyema in the absence of bronchopleural fistula and that intrathoracic muscle transposition to reinforce the bronchial stump is an effective procedure in the control of postpneumonectomy-associated bronchopleural fistula. J Otolaryngol, 1990 Jun, 19(3), 206 - 10 Vascular complication of neck space infection: case report and literature review; Stevens HE; Antibiotic therapy has changed the face of medicine radically, and physicians no longer have the empirical knowledge of bacterial infections that they once had . Consequently, the diagnosis and management of complicated infections presents a significant challenge to today's otolaryngologists . We present a rare complication, even before the advent of antibiotics, of a head and neck infection: a carotid artery pseudoaneurysm resulting from peritonsillar abscess . The diagnosis and management of this problem is discussed and the pertinent literature reviewed. Urology, 1990 Jun, 35(6), 533 - 6 Conservative therapy of rectourethral fistula: five-year follow-up; Thompson IM et al.; A case of rectourethral fistula is described, occurring after radical prostatectomy and adjuvant radiotherapy for pathologic Stage C carcinoma of the prostate . Urethral instrumentation for stricture disease immediately preceded development of the stricture . Conservative management for five years has resulted in the development of osteomyelitis of the pubis, but with antibiotic suppression the patient remains active and asymptomatic . Predisposing factors for the development of rectourethral fistula following radical prostatectomy may include adjuvant radiotherapy and recurrent urethral instrumentation . Most patients will require definitive repair but occasionally a patient may be managed conservatively. Ann Otol Rhinol Laryngol, 1990 Jun, 99(6 Pt 1), 427 - 31 Otitic candidiasis in children: an evaluation of the problem and effectiveness of ketoconazole in 10 patients; Cohen SR et al.; The purpose of this paper is to report a group of children with recurring ear infections in whom persistent otorrhea was found to be due to monilial (Candida) infection of the middle ear . Some of the patients had associated mastoid disease . A review of the literature reveals few reports of otitis media and/or mastoiditis due to Candida infection . Ten patients who had persistent otorrhea were found to have monilial infection as a cause of the ear disease . None of the patients were immunosuppressed or immunocompromised . Nine of the 10 patients (one was lost to follow-up) were treated with antifungal medication, and the effectiveness of ketoconazole therapy is evaluated . None of the children in this series had systemic candidiasis . The probable causes of the problem of yeast infection of the ear are explored and appear to be related to the use of multiple broad-spectrum antibodies and local antibiotic-steroid ear drops. Am J Surg, 1990 Jun, 159(6), 589 - 92 Appendicitis in children aged 13 years and younger; Gamal R et al.; During a recent 4 1/2-year period, an increasing number of young children aged 13 years and younger (230 consecutive patients) came to our institution with signs, symptoms, and findings of acute appendicitis, which was perforated in nearly half of the cases (47%) . This was accompanied by a marked increase in the number of very young children aged 6 years and younger (32% of our 230 patients) . A prompt response to broad preoperative antibiotic coverage and definitive operative intervention (appendectomy in all cases) was found, with no mortality and essentially no major morbidity (less than 1%) . The rapid transition from serious illness to near normalcy in the matter of a few hours with a standardized approach to treatment stimulated this review of appendicitis in this pediatric age group in an effort to define factors influencing these findings. Proc Natl Acad Sci U S A, 1990 Jun, 87(11), 4275 - 9 Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro; Ito H et al.; The anthracycline antibiotic doxorubicin produces a characteristic myopathy in cardiac muscle that limits its use in cancer therapy . We have shown in cultured neonatal rat cardiac muscle cells that doxorubicin treatment resulted in a rapid, selective decrease in the expression of muscle-specific genes, which preceded other changes characteristic of doxorubicin cardiomyopathy . Doxorubicin selectively and dramatically decreased the levels of mRNA for the sarcomeric genes, alpha-actin, troponin I, and myosin light chain 2, as well as the muscle-specific, but nonsarcomeric M isoform of creatine kinase . However, doxorubicin did not affect nonmuscle gene transcripts (pyruvate kinase, ferritin heavy chain, and beta-actin) . Actinomycin D, an inhibitor of DNA-dependent RNA polymerase, did not show a similar selective decrease of muscle-specific mRNAs but, rather, produced a nonspecific, dose-dependent decrease of muscle and nonmuscle transcripts . The doxorubicin effect on muscle gene expression was limited to cardiac muscle; cultured skeletal myocytes were resistant to the effects of doxorubicin at 100-fold greater doses than those causing changes in mRNA levels in cardiac muscle cells . These effects of doxorubicin were reproduced in vivo; rats injected with doxorubicin showed a dose-dependent decrease in the levels of mRNAs for alpha-actin, troponin I, myosin light chain 2, and M isoform of creatine kinase in cardiac but not skeletal muscle . These selective changes in gene expression in cardiocyte cultures and cardiac muscle precede classical ultrastructural changes and may explain the myofibrillar loss that characterizes doxorubicin cardiac injury. Virology, 1990 Jun, 176(2), 467 - 73 Pradimicin A inhibition of human immunodeficiency virus: attenuation by mannan; Tanabe-Tochikura A et al.; The mechanism of action of a novel anti-HIV antibiotic, pradimicin A, has been studied using cell-free (MT-4 cells) and cell to cell (MOLT-4 and MOLT-4/HIVHTLV-3B cells) HIV infection systems . The data indicate that (1) preincubation of the cells with HIV at 0 degrees for 1 hr, followed by the addition of pradimicin A and further incubation at 37 degrees, resulted in a complete inhibition of infection while preincubation at 37 degrees did not . Similar data were obtained with the coculture between MOLT-4 and MOLT-4/HIV cells . (2) Virus treated with pradimicin A followed by washing did not show any inhibition on subsequent HIV binding to cells . (3) The inhibitory effect of pradimicin A on HIV infection was prevented by mannan but not by other sugars tested . Mannan, however, did not interfere with the anti-HIV activity of other known inhibitors . (4) Use of EGTA suggested that pradimicin A required Ca ions to exert its anti-HIV activity . These data imply that pradimicin A inhibits an early step in HIV infection, probably through its binding to mannose residues of HIV glycoprotein. J Bacteriol, 1990 Jun, 172(6), 3427 - 34 Cloning and expression of daunorubicin biosynthesis genes from Streptomyces peucetius and S . peucetius subsp . caesius; Otten SL et al.; Genes for the biosynthesis of daunorubicin (daunomycin) and doxorubicin (adriamycin), important antitumor drugs, were cloned from Streptomyces peucetius (the daunorubicin producer) and S . peucetius subsp . caesius (the doxorubicin producer) by use of the actI/tcmIa and actIII polyketide synthase gene probes . Restriction mapping and Southern analysis of the DNA cloned in a cosmid vector established that the DNA represented three nonoverlapping regions of the S . peucetius subsp . caesius genome . These three regions plus an additional one that hybridized to the same probes are present in the S . peucetius genome, as reported previously (K . J . Stutzman-Engwall and C . R . Hutchinson, Proc . Natl . Acad . Sci . USA 86:3135-3139, 1989) . Functional analysis of representative clones from some of these regions in S . lividans, S . peucetius ATCC 29050, S . peucetius subsp . caesius ATCC 27952, and two of its blocked mutants (strains H6101 and H6125) showed that many of the antibiotic production genes reside in the region of DNA represented by the group IV clones . This conclusion is based on the production of epsilon-rhodomycinone, a key intermediate of the daunorubicin pathway, in certain S . lividans transformants and on the apparent complementation of mutations that block daunorubicin biosynthesis in strains H6101 and H6125 . Some of the transformants of strains 29050, 27952, and H6125 exhibited substantial overproduction of epsilon-rhodomycinone and daunorubicin. Exp Hematol, 1990 Jun, 18(5), 400 - 7 Migration of stem cells and progenitors between marrow and spleen following thiamphenicol treatment of mice; Goris H et al.; Recovery of hemopoiesis was studied after a 3-day treatment with the antibiotic thiamphenicol (TAP) . A contrasting behavior of the spleen colony-forming units (CFU-S), granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and erythroid colony-forming units (CFU-E) numbers in the bone marrow versus those in the spleen was found . Whereas the cell numbers reached nadirs in the marrow, they peaked 30 to 100-fold above control values in the spleen on day 4 . Simultaneously the number of CFU-S, BFU-E, and CFU-GM, but not of CFU-E, increased drastically in the peripheral blood . The tritiated thymidine kill of the splenic CFU-S was too small to explain the endogenous splenic production of these cells . A quantitative analysis further revealed that an effective erythropoiesis was established in the spleen . As a consequence, the first part of a reticulocytosis was mainly due to the splenic contribution, whereas the second part predominantly originated from a delayed marrow erythropoiesis . In contrast, the CFU-GM of the spleen did not effectively differentiate into granuloid precursors . The bulk of the granuloid production occurred in the marrow . The best explanation for these results is a net migration of CFU-S, BFU-E, and CFU-GM from the marrow to the spleen during early recovery, and a back-migration of CFU-GM to the marrow later in the recovery phase . These observations indicate a link between migration of hemopoietic cells and their differentiation at the two hemopoietic sites. Mycoses, 1990 Jun, 33(6), 283 - 90 Hepatosplenic candidosis--a late manifestation of Candida septicemia; von Eiff M et al.; Hepatolienal candidosis was diagnosed in 27 patients suffering from malignant hematologic disorders . All patients had received intensive cytostatic chemotherapy and developed septic, antibiotic-resistant temperatures during severe treatment-induced neutropenia . During neutropenia hepatic and splenic foci were not identified by imaging procedures . Foci were poorly defined histologically . Blastospores and pseudomycelia were seen in non-reactive tissue and within necrotic areas in the liver, spleen, and other organs . Only Candida species could be isolated . One to four weeks after granulocyte recovery, round liver and splenic foci were demonstrated by sonographic and CT scans . Histologically, there were necrotic areas with blastospores and pseudohyphae exhibiting different degrees of cellular border reaction . Whereas the maximum diameter of fungal foci in aplasia was 0.4 cm, these increased in size to 1.5 cm after granulocyte regeneration. Jpn J Antibiot, 1990 Jun, 43(6), 1152 - 63 {Studies on acetylspiramycin . 1 . Separation and chemical structures of acetylspiramycin components}; Kondo A et al.; 1 . A macrolide antibiotic acetylspiramycin (ASPM) was separated into seven fractions using high performance liquid chromatography (HPLC) with Lichrosorb RP-8 and mobile phase of a mixed solvent of 0.025M phosphate ammonium (pH 7.4) and acetonitrile at a ratio of 10:18 . 2 . Five components were purified over 90%, and analyzed using mass spectroscopy, 1H NMR, and 13C NMR, and their chemical structures were determined as 4''-acetylspiramycin I, 4''-acetylspiramycin II, 4''-acetylspiramycin III, 3'',4''-diacetylspiramycin II and 3'',4''-diacetylspiramycin III, respectively . 3 . The weight component ratio of the seven fractions of ASPM separated by HPLC was constant throughout several lots of ASPM which had been stocked for nearly 15 years at room temperature, indicating an excellent chemical stability of the antibiotic . 4 . Some physicochemical parameters were determined for the five ASPM components . Solubilities in water at 24 degrees C were in a range from 0.14 mg/ml to 4.9 mg/ml, and they were, in the decreasing order, 3'',4''-diacetylspiramycin III, 3'',4''-diacetylspiramycin I 4''-acetylspiramycin III, 4''-acetylspiramycin II, and 4''-acetylspiramycin I . Relationships between solubilities and numbers and positions of acyl substituents in spiramycin molecule are discussed. Bioorg Khim, 1990 Jun, 16(6), 847 - 53 {Synthesis and mass-spectrometric analysis of N-cycloalkyl derivatives of carminomycin, daunorubicin and their analogs}; Olsuf'eva EN et al.; Condensation of carminomycin or daunorubicin with glutaric dialdehyde in the presence of NaBH3CN yielded 3'-deamino-3'-piperidinocarminomycin or 3'-deamino-3'-piperidinodaunorubicin and corresponding (13-R, S)-dihydroderivatives . To prepare similar derivatives of 14-hydroxycarminomycin or doxorubicin, 13-dimethylketals of 14-bromocarminomycin or 13-bromodaunorubicin were used in the reaction of reductive alkylation with glutaric or glycolic dialdehyde to give 3'-deamino-3'-piperidino- or 3'-deamino-3'-morpholino derivatives of 13-dimethylketals of 14-bromocarminomycin or daunorubicin, respectively . After deblocking and subsequent hydrolysis of these compounds 3'-deamino-3'-piperidino- and 3'-deamino-3'-morpholino derivatives of 13-hydroxycarminomycin or doxorubicin were prepared . Reduction of the antibiotic derivatives under mass spectrometry conditions was demonstrated. Br J Clin Pract, 1990 Jun, 44(6), 242 - 3 Three 'silent' mastoid abscesses; Wickham MH et al.; Acute mastoiditis with abscess formation is uncommon, its incidence being modified by modern antibiotic usage for acute suppurative otitis media (ASOM) . It tends to occur in young children who have no previous history of ear disease . The diagnosis is a clinical one, and treatment requires hospital admission and some form of surgical drainage procedure, in order to prevent intracranial complications, eg, meningitis and intracerebral abscess. Mayo Clin Proc, 1990 Jun, 65(6), 819 - 24 Nocardia asteroides pericarditis: report of a case and review of the literature; Poland GA et al.; In this report, we describe a patient who had purulent Nocardia asteroides pericarditis . In addition, we identified 13 previously suspected and reported cases of Nocardia pericarditis, but only 5 of these studies reported isolation of Nocardia from cultures of pericardial fluid or pericardium . Analysis of the clinical course of these five patients and our patient revealed the importance of long-term sulfonamide antibiotic therapy in combination with surgical pericardial drainage procedures . In our review, only patients who received antibiotics and underwent pericardiectomy survived . Our case substantiates the excellent penetration of sulfisoxazole into the pericardial fluid, even with oral administration of the drug, and provides evidence in support of aggressive management of Nocardia pericarditis. J Arthroplasty, 1990 Jun, 5(2), 169 - 72 Cefuroxime in total joint arthroplasty . Intravenous or in bone cement; McQueen MM et al.; A prospective randomized clinical trial was performed in two centers to compare the effect of systemic cefuroxime and cefuroxime in bone cement in the prophylaxis of infection after total joint arthroplasty . In two comparable groups comprising 200 and 201 patients, there was no statistically significant difference in the incidence of superficial wound infection . The early deep infection rate was 1%, with no difference detected between the group that received antibiotic in bone cement and the group that received systemic antibiotic . There were no late deep infections . It is concluded that cefuroxime given systemically or in bone cement is an effective antibiotic in the prophylaxis of infection after total joint arthroplasty. Crit Care Nurs Clin North Am, 1990 Jun, 2(2), 167 - 78 Vasoactive drug therapy in shock; Burns KM; The process of supporting the patient in shock with vasoactive infusions is never a static one . There are a variety of vasoactive infusions available; unfortunately, no one medication effectively corrects the numerous abnormalities in all forms of shock and no magic formula exists for combining medications to achieve optimum tissue perfusion . The nurse is challenged to utilize keen assessment skills and sophisticated monitoring techniques to follow the patient's response to changing vasoactive drug therapy . The nurse must collaborate with the physician and other health team members to integrate drug therapy with the other aspects of shock therapy, including fluid repletion, oxygenation and ventilation, metabolic support, and antibiotic therapy to facilitate the successful resuscitation of the patient in shock. Clin Pharmacokinet, 1990 Jun, 18(6), 472 - 84 Pharmacokinetic drug interactions with oral contraceptives; Back DJ et al.; Oral contraceptive steroids are used by an estimated 60 to 70 million women world-wide . Over the past 20 years there have been both case reports and clinical studies on the topic of drug interactions with these agents . Some of the interactions are of definite therapeutic relevance, whereas others can be discounted as being of no clinical significance . Pharmacological interactions between oral contraceptive steroids and other compounds may be of 2 kinds: (a) drugs may impair the efficacy of oral contraceptive steroids, leading to breakthrough bleeding and pregnancy (in a few cases, the activity of the contraceptive is enhanced); (b) oral contraceptive steroids may interfere with the metabolism of other drugs . A number of anticonvulsants (phenobarbital, phenytoin, carbamazepine) are enzyme-inducing agents and thereby increase the clearance of the oral contraceptive steroids . Valproic acid has no enzyme-inducing properties, and thus women on this anticonvulsant can rely on their low dose oral contraceptive steroids for contraceptive protection . Researchers are now beginning to unravel the molecular basis of this interaction, with evidence of specific forms of cytochrome P450 (P450IIC and IIIA gene families) being induced by phenobarbital . Rifampicin, the antituberculous drug, also induces a cytochrome P450 which is a product of the P450IIIA gene subfamily . This isozyme is one of the major forms involved in 2-hydroxylation of ethinylestradiol . Broad spectrum antibiotics have been implicated in causing pill failure; case reports document the interaction, and general practitioners are convinced that it is real . The problem remains that there is still no firm clinical pharmacokinetic evidence which indicates that blood concentrations of oral contraceptive steroids are altered by antibiotics . However, perhaps this should not be a surprise, given that the incidence of the interaction may be very low . It is suggested that an individual at risk will have a low bioavailability of ethinylestradiol, a large enterohepatic recirculation and gut flora particularly susceptible to the antibiotic being used . Two drugs, ascorbic acid (vitamin C) and paracetamol (acetaminophen), give rise to increased blood concentrations of ethinylestradiol due to competition for sulphation . The interactions could have some significance to women on oral contraceptive steroids who regularly take high doses of either drug . Although on theoretical grounds adsorbents (e.g . magnesium trisilicate, aLuminium hydroxide, activated charcoal and kaolin) could be expected to interfere with oral contraceptive efficacy, there is no firm evidence that this is the case . Similarly, there is no evidence that smoking alters the pharmacokinetics of oral contraceptive steroids . These agents are now well documented as being able to alter the pharmacokinetics of other concomitantly administered drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PIP: The pharmacokinetics and clinical significance of the major drug interactions seen with oral contraceptives are reviewed, both drugs interfering with pill efficacy, and situations where pills interfere with action of other drugs . Drugs affecting contraceptive efficacy include anticonvulsants, antibiotics, rifampicin, griseofulvin, ascorbic acid, and acetaminophen . Phenytoin is the most common anticonvulsant reported to cause contraceptive failure . It as been established by measurements of steady-state ethinyl estradiol levels, sex hormone binding globulin levels, and pharmacokinetic drug concentration curves that both ethinyl estradiol and levonorgestrel levels are decreased during phenytoin and carbamazepine intake . Induction of certain cytochrome P450 isozymes is probably responsible . Neither the causation or even the existence of drug interaction with antibiotics is definitely known, although case reports of pregnancies abound . Rifampicin is an exception, where enzyme induction clearly occurs . Ascorbic acid and acetaminophen are atypical for increasing the therapeutic effect of ethinyl estradiol . The effect of benzodiazepines depends on the type of drug metabolism: drugs oxidized and nitroreduced, e.g . chlordiazepoxide, alprazolam, diazepam, and nitrazepam, exhibit reduced clearance during pill intake . Clearance of cyclosporin, prednisolone, alcohol, caffeine and theophylline are also slowed by orals . Pills accelerate clearance of salicylic acid and morphine . Semin Oncol, 1990 Jun, 17(3 Suppl 6), 24 - 8 Prophylaxis of candidiasis in cancer patients; Bodey GP et al.; Patients undergoing therapy for metastatic malignancies were randomly assigned to receive fluconazole or placebo as antifungal prophylaxis . Oropharyngeal candidiasis developed in 28% of 54 evaluable patients receiving placebo but in only 2% of 58 evaluable patients receiving fluconazole (P = .0003) . Among patients receiving placebo, oropharyngeal candidiasis (thrush) occurred in 30% of those receiving antibiotic therapy and in 44% of those receiving adrenal corticosteroid therapy . Oropharyngeal candidiasis developed in 54% of the placebo patients who were colonized by Candida sp at the onset of prophylaxis . Fluconazole proved to be effective for prophylaxis of oropharyngeal candidiasis in susceptible patients and was well tolerated. Dis Colon Rectum, 1990 Jun, 33(6), 520 - 7 Infectious enteritis . A collective review; Fry RD; Enteric infections are a major cause of diarrhea in the United States . Pathogens can cause diarrhea by elaboration of toxins that affect the intestinal mucosa or by direct invasion of the intestinal wall . Clinical evaluation can provide important clues to aid in establishing a correct diagnosis in most patients with infectious enteritis . Appropriate cultures are necessary to confirm the diagnosis in most cases . Most types of infectious enteritis are self-limiting, but some pathogens can cause serious disease, requiring accurate diagnosis and suitable antibiotic therapy . Appropriate precautions are mandatory to prevent the spread of infectious diarrhea from occurring in the hospital environment . Dietary restrictions and appropriate hygiene should be observed during travel to foreign countries to reduce the chance of acquiring infectious enteritis. Surg Clin North Am, 1990 Jun, 70(3), 561 - 73 Management of colon injuries; Huber PJ Jr et al.; The evaluation and management of colon injuries have recently undergone significant changes . The time-honored philosophy of conservative management by repair and diversion is giving way to a more aggressive approach, which includes primary repair of many injuries . The role of colostomy has been challenged by the need for additional operative procedures, patient disability, and rising hospital and medical costs . Based on the current literature, the authors have come to the following conclusions: 1 . Primary repair is safe in carefully selected cases . 2 . Colostomy should not be abandoned because of a fear of the morbidity associated with its closure . 3 . The difference between injuries on the right and the left is questionable and probably not as significant as previously thought . 4 . Exteriorized repair frequently requires conversion to colostomy and probably has little indication for use . 5 . Short-term perioperative single-antibiotic coverage is sufficient . 6 . Use of drains cannot be supported in most instances . 7 . Wounds are best left open in patients with significant contamination . Surgical judgment remains the final arbiter in the decision process . These controversies and the debate generated have sharpened the guidelines for that judgment. Cancer Res, 1990 Jun 1, 50(11), 3159 - 66 Immune response to progressor variants derived from transfection of an ultraviolet radiation-induced C3H mouse regressor tumor cell line with activated Harvey-ras oncogene; Kaba DS et al.; Skin cancers induced in mice by UV radiation often exhibit a regressor phenotype . In order to determine how tumors escape the immune defenses of the normal immunocompetent host, we sought to isolate progressor variants from a UV radiation-induced C3H mouse regressor fibrosarcoma cell line, UV-2240, by transfection with an activated Ha-ras oncogene . A cotransfection protocol using pSV2-neo DNA, which confers resistance to the antibiotic G418, was used to select transfected cells . Injection of Ha-ras-transfected UV-2240 cells s.c . into immunocompetent C3H mice produced tumors in four of 36 animals . In contrast, UV-2240 cells transfected with pSV2-neo DNA alone or mock transfected with CaPO4 did not produce tumors in normal C3H mice . DNAs from cell lines established from Ha-ras-induced tumors contained unique Ha-ras sequences in addition to those sequences endogenous to UV-2240 cells . However, the Ha-ras-induced progressor variants did not overexpress the Mr 21,000 protein . The Ha-ra-induced progressor variants produced experimental lung metastasis in both normal C3H and nude mice, although they induced more lung nodules in nude mice than in normal C3H mice . In addition, all four Ha-ras-induced progressor variants produced significantly more experimental lung metastases in nude mice than did the parent UV-2240 cell line . However, both the parental UV-2240 cell line and the Ha-ras-induced progressor variants expressed similar levels of H-2Kk and H-2Dk antigens and were immunologically cross-reactive, as determined by in vitro cytotoxic T-lymphocyte and in vivo immunization-challenge assays . These results indicate that the progressor phenotype of the Ha-ras-induced tumor variants is not due to loss of tumor-specific transplantation or Class I major histocompatibility complex antigens . This implies that some tumor cells can escape the immune defenses of the normal immunocompetent host by mechanisms other than loss of tumor-specific transplantation and Class I major histocompatibility antigens. Biochem Cell Biol, 1990 Jun, 68(6), 983 - 7 A rapid immunoprecipitation assay for neomycin phosphotransferase II expression in transformed bacteria and plant tissues; Baszczynski CL; Anti-kanamycin antibodies produced in rabbits, following coupling of the antibiotic to bovine serum albumin, were used to immunoprecipitate radioactively labelled phosphorylated kanamycin from transformed bacterial or plant extracts in a novel assay system, for the detection of neomycin phosphotransferase II (NPTII) activity . Radioactive counts in the immunoprecipitated pellet give a semiquantitative measure of the kanamycin phosphorylation and hence the amount of NPTII activity . This assay is sensitive, uses very small amounts of radioactivity, and is very rapid, allowing many samples to be processed within a few hours . Immunoprecipitated counts from reactions with bacteria carrying a kanamycin resistance gene or from tobacco and Brassica napus plants transformed with NPTII gene-containing vectors were consistently higher than counts from nontransformed controls . Results obtained with this assay correlate well with those from the previously described gel overlay and dot-blot assays, but can be obtained in an appreciably shorter time frame. J Mol Evol, 1990 Jun, 30(6), 489 - 92 Evolutionary origin of aminoglycoside phosphotransferase resistance genes; Kirby R; The protein sequences of seven 3'-aminoglycoside phosphotransferases falling into the six identified types and three 6'-aminoglycoside phosphotransferases were analyzed to give a rooted phylogenetic tree . This tree supports the origin of these groups of enzymes in an ancestor closely related to the actinomycetes, and that horizontal transfer of the resistance genes occurred, possibly via transposons . The implications for genetic engineering of a novel antibiotic are discussed. EMBO J, 1990 Jun, 9(6), 2011 - 6 Phospholipid biosynthesis and poliovirus genome replication, two coupled phenomena; Guinea R et al.; Poliovirus infection leads to an increase of phospholipid synthesis and the proliferation of new membranes, giving rise to a great number of cytoplasmic vesicles in the infected cells . Viral RNA replication is physically associated with these newly-synthesized membranes . Cerulenin, an inhibitor of lipid biosynthesis, effectively blocks the growth of poliovirus in HeLa cells . The presence of cerulenin after virus entry prevents the synthesis of poliovirus proteins . However, if this antibiotic is added at later stages of the virus replication cycle, it has no effect on viral translation itself, nor on the proteolytic processing and myristoylation of poliovirus proteins . The synthesis of viral, but not cellular RNA is selectively inhibited by cerulenin . Analysis of the viral RNA made in poliovirus-infected cells by specific minus-or plus-stranded RNA probes suggests a selective blockade by cerulenin of plus-strand RNA synthesis . Finally, the synthesis of phospholipids and the proliferation of membranes does not take place if cerulenin is added to the culture medium . These findings indicate that continuous phospholipid synthesis is required for efficient poliovirus genome replication and provide new insights towards the understanding of the molecular events that occur during poliovirus growth. J Bacteriol, 1990 Jun, 172(6), 3367 - 78 Cloning, disruption, and transcriptional analysis of three RNA polymerase sigma factor genes of Streptomyces coelicolor A3(2); Buttner MJ et al.; The rpoD gene of Myxococcus xanthus was used as a probe to isolate three Streptomyces coelicolor genes, hrdB, hrdC, and hrdD, which appear to encode RNA polymerase sigma factors extremely similar to the sigma 70 polypeptide of Escherichia coli . Gene disruption experiments suggested that hrdB is essential in S . coelicolor A3(2) but showed that hrdC and hrdD mutants are viable and are apparently unaffected in differentiation, gross morphology, and antibiotic production . S1 nuclease mapping showed that hrdB and hrdD, but not hrdC, were transcribed in liquid culture . The most upstream of two hrdD promoters is internal to an open reading frame (ORF X) on the opposite strand . The predicted product of this gene is homologous to the phosphinothricin acetyltransferases of Streptomyces hygroscopicus and Streptomyces viridochromogenes . The possible significance of the overlapping and divergent transcription of hrdD and ORF X is discussed . A general method for in vivo gene replacement was developed that allowed a positive selection for the desired mutants even in the absence of a mutant phenotype; it was used to isolate a stable hrdC mutant. J Bacteriol, 1990 Jun, 172(6), 3066 - 72 Carboxyphosphonoenolpyruvate phosphonomutase, a novel enzyme catalyzing C-P bond formation; Hidaka T et al.; An enzyme catalyzing the formation of an unusual C-P bond that is involved in the biosynthesis of the antibiotic bialaphos (BA) was isolated from the cell extract of a mutant (NP71) of Streptomyces hygroscopicus SF1293 . This enzyme, carboxyphosphonoenolpyruvate (CPEP) phosphonomutase, was first identified as a protein lacking in a mutant (NP213) defective in one of the steps in the pathway to BA . The first 30 residues of the amino terminus of this protein were identical to those predicted by the nucleotide sequence of the gene that restored BA production to NP213 . The substrate of the enzyme, a P-carboxylated derivative of phosphoenolpyruvate named CPEP, was also isolated from the broth filtrate of NP213 as a new biosynthetic intermediate of BA . CPEP phosphonomutase catalyzes the rearrangement of the carboxyphosphono group of CPEP to form the C-P bond of phosphinopyruvate. J Virol, 1990 Jun, 64(6), 3135 - 8 Rapid titration of retroviral vectors encoding intracellular antigens by flow cytometry; Sladek TL et al.; Flow cytometry was used to detect cells infected with retroviral vectors encoding both simian virus 40 large T antigen and G418 resistance after indirect immunofluorescence staining using a T-antigen-specific monoclonal antibody and a fluorescein-conjugated secondary antibody . Titers of viral stocks determined by flow cytometry were equivalent to those determined by quantitation of G418-resistant colonies. Higashi Nippon Shigaku Zasshi, 1990 Jun, 9(1), 29 - 36 {Treatment of a refractory chronic osteomyelitis of the jaw}; Muto T et al.; Two cases of refractory chronic osteomyelitis of the jaw were presented, the first in a patient with pycnodysostosis, the second that had been receiving radiotherapy . Both cases were primary chronic osteomyelitis with a markedly protracted course of recovery, in spite of the antibiotic and local irrigation therapy . However the lesion was cured by the removal of sequesters and granulation tissues without radical treatment such as a decorticotomy . Radical surgery, decortication, is an effective procedure in the treatment of chronic osteomyelitis of the jaw, but treatment with the surgical procedures which remove only the necrotic bones and granulation tissues followed by antibiotic therapy is also possible. Clin Pharmacol Ther, 1990 Jun, 47(6), 671 - 4 A model to detect interactions between roxithromycin and oral contraceptives; Meyer B et al.; Twenty-two healthy women participated in a study to determine whether roxithromycin (a new macrolide antibiotic agent) obtunds the activity of a triphasic oral contraceptive . The duration of the study was four menstrual cycles . Medication was given as follows: (1) cycle 1, no medication to demonstrate ovulation; (2) cycle 2, triphasic oral contraceptive daily to suppress ovulation; (3) cycle 3, triphasic oral contraceptive daily plus roxithromycin, 150 mg b.i.d.; and (4) cycle 4, triphasic oral contraceptive daily plus rifampin, 300 mg daily . Sonography of the ovaries was performed on day 13, and serum progesterone was measured on day 21 of each cycle . Elevated progesterone indicated ovulation . The presence of a maturing follicle supported this finding . All volunteers ovulated in the first cycle and no volunteers ovulated in the second and third cycles . However, 11 women ovulated when rifampin and the triphasic oral contraceptive were given concomitantly . The findings suggest there is no reason to believe that roxithromycin interferes with the efficacy of oral contraceptives. Actual Odontostomatol (Paris), 1990 Jun, 44(170), 285 - 98 {Use of NHAI via mesotherapy in oral surgery}; Einholtz B et al.; In usual stomatologic surgery, after the intervention, the antibiotic cover is preserved but the classical anti-inflammatory cover is replaced by a unique session of multi-micro-injections of injectable Voltaren around the sutures into the mucous membrane . The results are similar on oedema, better on pain and this obtained with about ten times less NHAI, so much the better for side-effects. Pol Tyg Lek, 1990 May 21-28, 45(21-22), 417 - 20 {Assessment of the efficacy of treating infections in hematopoietic proliferative diseases: Monotherapy with ceftazidime and tobramycin combined with amoxycillin/ampicillin}; Koehler M et al.; Efficacy of the ceftazidime monotherapy in 120 febrile children with neoplastic diseases and granulocytopenia was compared with that of tobramycin combined with amoxycillin/ampicillin . The obtained results were similar in both types of antibiotic therapy . However, granulocytopenia was higher and septicemia was more frequent in children treated with ceftazidime . Isolated bacteria were more sensitive to ceftazidime than to tobramycin with amoxycillin/ampicillin . Both regimens were tolerated well . Despite a low number of patients in both groups, one may conclude that ceftazidime is more efficient in patients with granulocytopenia . Less adverse reactions, lower number of infections, less frequent medical procedures, elimination of the potentially toxic aminoglycosides and lower cost of therapy advocate the use of ceftazidime monotherapy. Schweiz Med Wochenschr, 1990 May 19, 120(20), 742 - 4 {Blastocystis hominis in feces . An assessment of 56 cases}; Krech T et al.; Over a twelve-month period all 3918 stool samples sent to our institute were investigated for Blastocystis hominis . This protozoon was detected in 384 samples . The stools of 50 healthy controls were negative . In 56 positive cases detailed clinical information was obtained: 26 of these patients had diarrhea, while only extraintestinal symptoms had been recorded in 10 cases . Blood eosinophilia was observed in 8 patients . Of 16 specifically treated patients, 10 responded to therapy . Although the pathogenic significance of B . hominis is still unclear, we believe our observations justify antibiotic therapy in selected cases. J Am Vet Med Assoc, 1990 May 15, 196(10), 1635 - 8 Surgical repair of ruptured trachea in a horse; Kirker-Head CA et al.; An Arabian mare was referred with traumatically induced complete transection of the trachea . A temporary airway was established through the open wound at the site of the rupture . Resection of devitalized tissue including 3 tracheal ring segments, and anastomosis of the tracheal ends was subsequently performed under general anesthesia . Wound healing was complicated by a peritracheal abscess, which responded successfully to drainage and antibiotic administration. Med Clin (Barc), 1990 May 12, 94(18), 689 - 92 {Rhinosporidiosis: presentation of 4 cases}; Gonzalez Nunez MA et al.; We report 4 cases of rhinosporidiosis in the province of Caceres . Two had nasal localization and in two ocular conjunctiva was involved . Three patients, two of which came from the same village, had the antecedent of bathing in the same stagnant water . The diagnosis was made by the microscopic observation of characteristic sporangia of Rhinosporidium seeberi in the histopathological study . The lesions did not respond to antibiotic and antiinflammatory treatment . After excision there were no recurrences, and the patients are asymptomatic after 1 1/2 year follow up. J Mol Biol, 1990 May 5, 213(1), 167 - 86 Refined crystal structure of type III chloramphenicol acetyltransferase at 1.75 A resolution; Leslie AG; High level bacterial resistance to chloramphenicol is generally due to O-acetylation of the antibiotic in a reaction catalysed by chloramphenicol acetyltransferase (CAT, EC 2.3.1.28) in which acetyl-coenzyme A is the acyl donor . The crystal structure of the type III enzyme from Escherichia coli with chloramphenicol bound has been determined and refined at 1.75 A resolution, using a restrained parameter reciprocal space least squares procedure . The refined model, which includes chloramphenicol, 204 solvent molecules and two cobalt ions has a crystallographic R-factor of 18.3% for 27,300 reflections between 6 and 1.75 A resolution . The root-mean-square deviation in bond lengths from ideal values is 0.02 A . The cobalt ions play a crucial role in stabilizing the packing of the molecule in the crystal lattice . CAT is a trimer of identical subunits (monomer Mr 25,000) and the trimeric structure is stabilized by a number of hydrogen bonds, some of which result in the extension of a beta-sheet across the subunit interface . Chloramphenicol binds in a deep pocket located at the boundary between adjacent subunits of the trimer, such that the majority of residues forming the binding pocket belong to one subunit while the catalytically essential histidine belongs to the adjacent subunit . His195 is appropriately positioned to act as a general base catalyst in the reaction, and the required tautomeric stabilization is provided by an unusual interaction with a main-chain carbonyl oxygen. Aust N Z J Ophthalmol, 1990 May, 18(2), 221 - 3 An unusual intracerebral foreign body associated with eye trauma; Lawson D et al.; A case report is presented of penetrating orbital trauma in the driver of a motor vehicle which collided with a kangaroo . A tooth fragment from the kangaroo traversed the orbit, lodging intracranially . Management of the case is described and appropriate choice of antibiotic regime discussed. Antibiot Khimioter, 1990 May, 35(5), 25 - 7 {General toxic and organotropic properties of cefotaxime in acute and chronic experiments}; Berezhinskaia VV et al.; The action of cefotaxime on the functions of the liver and kidneys, the peripheral blood count, growth and development of young animals, blood circulation, respiration and the central nervous system was studied in acute and chronic experiments on mice and rats . Allergenic, immunomodulating, embryotoxic and teratogenic properties of the antibiotic were also studied . Cefotaxime was shown to be low toxic . After intravenous administration to mice, its LD50 amounted to 7000 (6295-7805) mg/kg . In the chronic experiments on rats with intramuscular and intravenous administration of the antibiotic in doses equivalent by the body surface to the course doses for humans there were no significant shifts in the function of the liver and kidneys, the count of the blood formed elements and the histologic pattern of the viscera . In the therapeutic doses the antibiotic had no action on hemopoiesis, respiration and the central nervous system . The allergenic properties of cefotaxime were slightly pronounced and similar to those of klaforan . The antibiotic had no action on the host immunity and showed no embryotoxic and teratogenic properties . After intravenous and intramuscular administration, cefotaxime had a slight irritating action on the tissues which was similar to that of klaforan. Thorax, 1990 May, 45(5), 401 - 2 Concentrations of cefixime in bronchial mucosa and sputum after three oral multiple dose regimens; Baldwin DR et al.; In a study of 58 patients the concentrations of cefixime, a new oral cephem antibiotic, in bronchial mucosa were 35-40% of the concentrations found in simultaneously collected serum samples . The antibiotic was often undetectable in sputum despite a highly sensitive assay. Kinderarztl Prax, 1990 May, 58(5), 227 - 32 {Bacterial heart diseases in childhood . An overview of diseases 1971-1987}; Meister EM et al.; The authors give a review of patients with bacterial cardiac disease treated in the Paediatric Clinic of Karl-Marx-University Leipzig between 1971 and 1987 . During this period 32 patients were observed, which amounts to about 2 to 3 patients per year . The majority of patients had congenital heart disease . Despite antibiotic therapy the prognosis of this infection is still serious: One third of the patients died, and diagnosis is made with considerable delay in some cases . Problems and diagnostic and therapeutic approaches are discussed. Klin Monatsbl Augenheilkd, 1990 May, 196(5), 405 - 6 {Hydrogel, a new galenic form in ophthalmology}; Kaiser RR et al.; Good tolerance, long intervals of application and an excellent adhesion are the properties of viscous eye drops (Hydrogels) . The use of fusidic acid as a hydrogel in the treatment of bacterial eye infections guarantees a long-lasting antibiotic concentration in tear fluid . When given twice daily, there will be sufficient concentration of the antibiotic in all important tissues of the eye and at the same time it increases the patient compliance. J Hepatol, 1990 May, 10(3), 327 - 31 Culture-negative neutrocytic ascites: a less severe variant of spontaneous bacterial peritonitis; Pelletier G et al.; The clinical signs and symptoms, the biological data and the prognosis of 38 cirrhotic patients with culture-positive spontaneous bacterial peritonitis and 15 cirrhotic patients with culture-n