Cancer Res, 1986 Aug, 46(8), 4171 - 7 Abnormally banded chromosomal regions in doxorubicin-resistant B16-BL6 murine melanoma cells; Slovak ML et al.; B16-BL6 murine melanoma cells were selected for cytogenetic evaluation during the stepwise development of increasing resistance in vitro to the antitumor antibiotic, doxorubicin (DOX) . Karyotypic studies demonstrated extensive heteroploidy with both numerical and structural abnormalities which were not present in the parental DOX-sensitive B16-BL6 cells . Trypsin-Giemsa banding revealed the presence of several marker chromosomes containing abnormally banding regions (ABRs) in the 44-fold B16-BL6 DOX-resistant subline . These ABRs appeared to be more homogeneously staining at the higher DOX concentrations . Length measurements (ABR index) in seven banded metaphases indicated a direct correlation with increasing DOX concentration . When the DOX-resistant cells were grown in drug-free medium for 1 yr, the drug-resistant phenotype gradually declined in parallel with the level of resistance and the ABR index . DOX-induced cytogenetic damage examined by sister chromatid exchange methodology in parental B16-BL6 cells indicated a linear sister chromatid exchange:DOX dose-response relationship . However, after continuous treatment of parental B16-BL6 cells with DOX (0.01 microgram/ml) for 30 days, sister chromatid exchange scores were found to return to base-line values . The B16-BL6 resistant cells demonstrated a cross-resistant phenotype with N-trifluoroacetyladriamycin-14-valerate, actinomycin D, and the Vinca alkaloids but not with 1-beta-D-arabinofuranosylcytosine . The results suggest that ABR-containing chromosomes in DOX-resistant sublines may represent cytogenetic alterations of specific amplified genes involved in the expression of DOX resistance . Further studies are required to identify and define the possible gene products and to correlate their relationship to the cytotoxic action of doxorubicin. Jpn J Antibiot, 1986 Aug, 39(8), 2263 - 71 {Fundamental and clinical studies on ceftazidime in the perinatal period}; Yamamoto T et al.; Fundamental and clinical studies were carried out on ceftazidime (CAZ) in the perinatal period, and the results obtained were summarized below . Following bolus intravenous injection of CAZ 2 g, maternal serum concentrations of CAZ were as high as 145.3 +/- 17.2 micrograms/ml (mean +/- S.D.) at about 10 minutes, and then gradually decreased to 46.7 micrograms/ml at 2 hours, 5.31 micrograms/ml at 5 hours and 4 minutes, and 1.54 micrograms/ml at 11 hours and 10 minutes . The CAZ was detected in umbilical cord serum immediately after the administration, and concentrations were 31.0 +/- 1.54 micrograms/ml at about 10 minutes . Although the concentrations gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and later and was 3.00 micrograms/ml at 11 hours and 10 minutes . The CAZ was detected in amniotic fluid a little later than in umbilical cord serum, and concentrations of CAZ in amniotic fluid were as low as 1.50 +/- 0.67 micrograms/ml at about 10 minutes after the administration . Concentrations then gradually increased to 12.8 micrograms/ml at 2 hours and 26.5 micrograms/ml at 5 hours and 4 minutes, and even at 11 hours and 10 minutes, they were as high as 14.2 micrograms/ml . The above results demonstrated that the transfer of CAZ through placental barrier was very rapid and satisfactory . Also, CAZ showed good transfer into amniotic fluid, as well as sufficient retention, and was considered to be an effective antibiotic for prophylaxis of both fetal infections and amniotic fluid infections.(ABSTRACT TRUNCATED AT 250 WORDS) Jpn J Antibiot, 1986 Aug, 39(8), 2225 - 46 {Pharmacokinetic and clinical studies of ceftazidime in perinatal period}; Cho N et al.; Pharmacokinetic studies and clinical evaluations of ceftazidime (CAZ) were carried out in perinatal mothers and infants, and following results were obtained . The CAZ was promptly absorbed after intravenous injection or intravenous drip infusion in pregnant women, producing dose-related peak serum levels . Placental transference to the fetus was good . After intravenous injection or intravenous drip infusion of 1.0-2.0 g of CAZ, drug concentration in umbilical serum and amniotic fluid exceeded MICs of CAZ against main pathogenic organisms . Levels of CAZ in umbilical serum ranged 0.2-15.6 micrograms/ml after 1.0 g intravenous injection or intravenous drip infusion, and 0.7-27.2 micrograms/ml after 2.0 g intravenous injection, and those in amniotic fluid were 1.4-21.3 micrograms/ml after 1.0 g administration and 2.0-27.0 micrograms/ml after 2.0 g administration . According to the above results, it is possible to successfully prevent or treat perinatal infections by twice a day administration of CAZ at 1.0-2.0 g/dose . Clinically, CAZ was effective in the treatment of perinatal infections and the prophylaxis of intrauterine amniotic infection without any side effect . Moreover, newborn infants delivered from mothers receiving CAZ treatment did not have any abnormalities in laboratory test . The penetration of CAZ into mother's milk was low, thus the transfer of CAZ from milk to newborn infants should be low . The above results demonstrated that CAZ is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections. J Antibiot (Tokyo), 1986 Aug, 39(8), 1123 - 34 Further studies on the biosynthesis of chlorothricin; Lee JJ et al.; Feeding experiments with {U-13C3}- and (2R)-{1-2H2}glycerol showed that glycerol is incorporated intact into carbon atoms 22, 23 and 24 of the aglycone of chlorothricin . C-1 of glycerol gives rise to C-22 with retention of one atom of deuterium, which occupies the H-22R position . A mechanism for the assembly of the aglycone is proposed which invokes phosphoenolpyruvate as the direct precursor of the 3-carbon moiety and a Baeyer-Villiger oxidation as the mode of formation of the macrocyclic lactone functionality . A feeding experiment with {1,2-13C2}succinate suggests that the propionate units of the aglycone polyketide are formed entirely via the methylmalonyl-CoA mutase reaction . The formation of the two 2,6-dideoxy-D-rhamnose moieties of chlorothricin from glucose was shown to involve replacement of the 2-hydroxyl group of the sugar by hydrogen with inversion of configuration at C-2 . This contrasts with the retention stereochemistry observed earlier for the analogous formation of the 2,6-dideoxyhexose moiety of the antibiotic granaticin. J Med Microbiol, 1986 Aug, 22(1), 85 - 7 Increased detection of polymicrobial septicaemia by repeat subculture; Spencer RC et al.; Repeated subcultures were performed on 572 blood cultures that had yielded single significant organisms and 55 from which contaminants had grown . This yielded 83 more isolates from 71 patients . Only one of the contaminated blood cultures yielded a further significant isolate . Additional antibiotic therapy was indicated in only six patients . Although repeated subculture increased the detection of additional isolates, it did not help in the management of most patients. Gastroenterology, 1986 Aug, 91(2), 461 - 3 Tularemic hepatitis presenting as obstructive jaundice; Ortego TJ et al.; A 56-yr-old man was admitted for evaluation of fever, chills, jaundice, and alcoholic stools . Laboratory studies suggested a cholestatic process . Ultrasonography, computed tomography, and transhepatic cholangiography failed to reveal any abnormalities . Acute infection with Francisella tularensis was confirmed serologically, and a liver biopsy revealed cholestatic hepatitis with focal coagulative necrosis . Recovery was coincident with antibiotic therapy. Clin Orthop, 1986 Aug, (209), 185 - 8 Gentamicin-induced ototoxicity complicating treatment of chronic osteomyelitis; Esterhai JL Jr et al.; Ototoxicity, though a significant disabling complication of aminoglycoside antibiotic therapy, is monitored infrequently . Chronic osteomyelitis patients treated with an aminoglycoside are in a group at higher risk due to the length of therapy and large total dose of drug required for treatment . Serum levels of gentamicin should be maintained within therapeutic ranges but below toxic levels . Gentamicin ototoxicity is vestibular in two thirds of patients and cochlear in one third . One half of the patients with cochlear toxicity also have vestibular symptoms . Symptoms are often vague, insidious in onset, and masked by the critical presentation of the primary infectious process . Symptoms may occur immediately upon initiation of therapy, any time during the course of treatment, or after administration has been completed . The development of toxicity should be monitored on a regular basis by specifically asking the patient whether there has been any subjective hearing loss, ear fullness, tinnitus, or vertigo supplemented by pretreatment and follow-up audiogram and electronystagmogram (ENG) . Therapy should be discontinued at the first sign of alteration of cochlear or vestibular function . Ototoxic recovery occurs in only about 50% of the patients affected. J Antimicrob Chemother, 1986 Aug, 18(2), 199 - 201 Pefloxacin concentrations in human aqueous humour and lens; Salvanet A et al.; In 20 patients undergoing cataract extraction, we measured pefloxacin concentrations in the eye . After a 1 h infusion of pefloxacin 400 mg iv, the mean pefloxacin concentrations 2, 6, 12 and 24 h post-infusion were 0.75, 1.45, 1.04 and 0.86 mg/l, respectively . The simultaneous mean pefloxacin concentrations in the lens were 0.09, 0.20, 0.26 and 0.43 mg/l, respectively . The adequate penetration of pefloxacin into uninfected aqueous humour and lens suggests that this antibiotic may be effective in the treatment of certain bacterial endophthalmic infections. J Bacteriol, 1986 Aug, 167(2), 581 - 6 Anthracycline metabolites of tetracenomycin C-nonproducing Streptomyces glaucescens mutants; Yue S et al.; Mutants of Streptomyces glaucescens GLA.0 which are blocked in the production of tetracenomycin C (compound 1), an anthracycline antibiotic having significant antitumor activity, accumulated several new anthracycline metabolites structurally related to compound 1 and to intermediates of its biosynthetic pathway . Through chemical and spectroscopic comparisons with the known anthracycline metabolites of the wild-type strain, we identified the two regioisomers of tetracenomycin B2 (compounds 7a and 7b), 8-demethyltetracenomycin C (compound 12), tetracenomycin D2 (compound 11), tetracenomycin E (compound 13), and the 12-naphthacenone forms of compounds 7a, 7b, and 2 (tetracenomycin D1) . A hypothetical biosynthetic pathway to compound 1 is presented that is consistent with the occurrence of compounds 7b, 13, and 5 (tetracenomycin A2) and with the cosynthetic behavior of tetracenomycin C-nonproducing mutants (H . Motamedi, E . Wendt-Pienkowski, and C . R . Hutchinson, J . Bacteriol . 167:575-580, 1986). Cancer Treat Rep, 1986 Aug, 70(8), 967 - 9 Phase II evaluation of aclarubicin in refractory adult acute leukemia: a Southwest Oncology Group Study; Dabich L et al.; Aclarubicin, a new anthracycline antibiotic, was used to treat 24 adult patients with refractory adult leukemia, using a total dose of 300 mg/m2 (75 mg/m2/day X 4) . There were 20 patients with acute myelogenous and four with acute lymphoblastic leukemia . Approximately two-thirds of the patients had a Karnofsky score of less than or equal to 2, and two-thirds had received two or more previous induction programs . Interim bone marrow evaluation was obtained in 18 of 30 remission induction courses and revealed marked hypocellularity in 14, inadequate specimens in three, and persistent disease in one . Seven patients received more than one course . Two patients refused further therapy . In patients with myelogenous leukemia, there were two complete remissions lasting 10 and 16 months and one partial remission lasting 4 1/2 months . There were no responders in patients with lymphoblastic leukemia . Toxicity included profound leukopenia and thrombocytopenia, moderate nausea and vomiting, diarrhea, and mucositis . There were no cardiac symptoms associated with the drug infusion, but there were three late events possibly associated with anthracycline cardiotoxicity . Used in this dosage schedule, aclarubicin is an active, but toxic, agent in the acute myelogenous leukemias. Br J Haematol, 1986 Aug, 63(4), 625 - 36 Prediction of response of patients with acute nonlymphocytic leukaemia to remission induction therapy: use of clinical measurements; Preisler HD et al.; Two hundred patients with acute nonlymphocytic leukaemia received remission induction therapy consisting of cytosine arabinoside and an anthracycline antibiotic . Analysis of the pretherapy characteristics of the patients demonstrated that patient age was the most important factor in determining whether or not the patient would survive remission induction therapy . Assessment of the characteristics of the bone marrow after 6 d of therapy permitted the recognition of patients who were likely to fail to enter remission because of persistent leukaemia . Taken together, these observations demonstrate that it is possible to identify patients for whom conventional chemotherapy is not likely to be of benefit either because it is too intensive or because it is not intensive enough to produce a complete remission. Nippon Seikeigeka Gakkai Zasshi, 1986 Aug, 60(8), 941 - 50 {Sternocostoclavicular hyperostosis: a report of nineteen cases with special reference to its etiology and treatment}; Chigira M; Nineteen patients with sternocostoclavicular hyperostosis were reviewed retrospectively . Of particular interest were their responses to antibiotics and prostaglandin inhibitors . The prostaglandin inhibitors relieved the pain within four weeks in 16 of 18 patients . In most cases, however, the inhibitors gradually became less effective . Oral antibiotics were more effective than the inhibitors in relieving the pain in 8 of 10 patients who were given antibiotics . Pustulosis palmaris et plantaris, commonly associated with sternocostoclavicular hyperostosis, diminished after antibiotic therapy as did the chest pain in most cases . The similarities between age and sex distribution, and the responses to antibiotics of the patients with sternocostoclavicular hyperostosis and those with pustulosis suggest that these disorders have a common etiology, and that the pustulosis may represent "bacterid reaction", and the hyperostosis may also be a manifestation of a systemic reaction to a focal infection. J Neurosci, 1986 Aug, 6(8), 2322 - 6 The role of calcium in the rapid adaptation of an insect mechanoreceptor; French AS; The femoral tactile spine of the cockroach is a rapidly adapting mechanoreceptor in which the response to a step displacement is a burst of action potentials lasting about 1 sec . This adaptation seems to occur during the encoding of action potentials from receptor current, since there is no evidence of adaptation in the receptor potential, and the adaptation can be demonstrated by direct electrical stimulation of the single sensory neuron in the spine . We have recently presented evidence for a calcium-activated potassium conductance in the tactile spine receptor neuron, although it was not directly linked to adaptation . Since this conductance could be involved in the rapid adaptation of the tactile spine neuron, we sought an association between adaptation and the entry of calcium ions into the cell . Adaptation in the tactile spine neuron was examined by direct electrical stimulation using a randomly fluctuating current followed by frequency-response analysis . The dynamic behavior was studied as a function of the concentration of calcium ions in the bathing solution, the presence of calcium channel blocking agents, or the divalent cation ionophore antibiotic A23187 . No evidence could be found that entry of calcium ions into the cell has a major role in the sensory adaptation. J Clin Lab Immunol, 1986 Aug, 20(4), 167 - 70 The effect of clindamycin on macrophage and monocyte Fc receptors; Oliver AM et al.; The effect of clindamycin on Fc receptor expression has been investigated with mouse peritoneal macrophages and human peripheral blood monocytes . When monolayers of these cells were treated with therapeutic concentrations of clindamycin for periods up to 1 hr at 37 degrees C binding of IgG2b coated sheep erythrocytes (EAG) was inhibited . No effect was observed at 4 degrees C or 22 degrees C . An independent effect of the antibiotic on the sheep erythrocytes was noted when they were pretreated with clindamycin that resulted in enhanced binding to the mouse but not the human phagocytes . These findings are discussed in relation to possible in vivo actions of the antibiotic. Aktuelle Traumatol, 1986 Aug, 16(4), 153 - 7 {Homologous transplantation of spongiosa . Evaluation following 2 1/2 years}; Gollwitzer M; Sufficient stability in comminuted fractures of the lower limb, in correcting bone axis or in hip surgery can often be achieved only by adjunctive transplantation of cancellous bone . The homologous cancellous bones is cut to chips out of extracted femoral heads and frozen in a bone bank at -30 degrees C . The homologous material is available whether or not the patient himself has enough autologous spongiosa . Establishing a bone bank in a small hospital can be done with small effort and works well, as experience shows . Immunological phenomena do not cause any problems although they are responsible for the prolonged incorporation of homologous spongiosa . Out of 41 cases with such a transplantation 26 showed healing without complications, 5 weak or severe tissue reactions . 2 of 4 patients with existing infections prior to transplantation could be stabilised . 6 patients were infected after implantation of spongiosa . The condition of the soft tissue and the status of immunity in aged persons played an important role . Possibly the number of infections can be reduced by rinsing the spongiosa in antibiotic solution before implantation. Biochemistry, 1986 Jul 29, 25(15), 4337 - 44 Reassignment of the guanine-binding mode of reduced mitomycin C; Tomasz M et al.; Mitomycin C (1) is a clinically used antitumor antibiotic that binds covalently to deoxyribonucleic acid under reductive or acidic catalysis . We have determined the structures of the adducts resulting from attack of reductively activated 1 on the dinucleoside phosphate d(GpC) to be N2-(2'' beta, 7''-diaminomitosen-1''alpha-yl)-2'-deoxyguanosine (2) and its 1'' beta-isomer (3) . This represents a revision of the previously reported structures for these adducts in that the mitomycin residue is linked to the N2- rather than O6-position of 2'-deoxyguanosine . This revision is the result of applying to the mitomycin case a newly developed general method that leads to unambiguous assignment of the linkage position in complex alkylated guanosines . The method as described here takes advantage of the resolution enhancement gained by calculation of the second derivatives of absorbance Fourier transform infrared spectra . In addition, we present 1H NMR data that corroborate the assigned structures of 2 and 3 and that should serve as a useful reference for future investigations into the binding of mitomycin C to DNA . The convenient synthesis of adducts 2 and 3 from deoxyguanosine and mitomycin C reported here should facilitate such investigations as well . Furthermore, we demonstrate a useful acetylation procedure for adducts and metabolites of mitomycin C that furnishes spectroscopically superior chemical derivatives (e.g., triacetates 4 and 5, derived from acetylation of adducts 2 and 3). Biochemistry, 1986 Jul 29, 25(15), 4349 - 56 Nucleotide sequence binding preferences of nogalamycin investigated by DNase I footprinting; Fox KR et al.; Four DNA restriction fragments, designated tyrT, pTyr2, pUC13, and Xbs1, have been used as substrates for footprinting studies with DNase I in the presence of the anthracycline antibiotic nogalamycin . With each fragment a distinct pattern of antibiotic-protected binding sites is observed, but no concensus sequence emerges from the data . All sites are located in regions of alternating purine-pyrimidine sequence, most commonly associated with the dinucleotide steps TpG (CpA) and GpT (ApC), suggesting that the preferred binding sites may contain all four nucleotides and/or that peculiarities of the dynamics of DNA conformation at alternating sequences may be critical for nogalamycin binding . Some concentration dependence of footprinting patterns is evident, in contrast to previous studies with a variety of sequence-specific ligands . Enhanced susceptibility to attack by DNase I is commonly observed at sequences flanking strong antibiotic-binding sites . Nogalamycin selectively inhibits cleavage of DNA at certain guanine-containing sequences by the G-specific photosensitized reaction with methylene blue . Comparison of these effects with its action on the G-specific reaction with dimethyl sulfate suggests that the amino sugar moiety of nogalamycin may be preferentially located in the minor helical groove at some binding sites but in the major groove at others. Nature, 1986 Jul 24-30, 322(6077), 385 - 7 Expression of human adenosine deaminase in murine haematopoietic progenitor cells following retroviral transfer; Belmont JW et al.; Adenosine deaminase (ADA) deficiency, an autosomal recessive inborn error of metabolism, leads to severe combined immune deficiency in man . This enzyme, although constitutively expressed in most tissues, is expressed at high level in immature T cells, and study of the pathophysiology of the disorder indicates that increased deoxyadenosine or altered methylation capacity have toxic effects on T-cell maturation . Although bone marrow transplantation can correct the immune deficiency, this therapy is associated with graft-versus-host disease and incomplete immune restoration, and so our laboratory and others have sought to develop a method of gene replacement as a possible treatment for the disease . Moreover, characterization of the complementary DNA of the human ADA gene and some of its mutants makes it possible to design gene transfer strategies . We have now subcloned a human adenosine deaminase cDNA into the retrovirus shuttle vector pZIP-SV(B), and in this way have isolated a cell line, 4.2T, which produces high titres of replication-defective retrovirus which have been used to transfer the gene for human ADA to mouse bone marrow cells . Transfer and expression of the neomycin-resistance gene (neo) and the ADA gene in murine bone marrow colony-forming units (CFU) was demonstrated by in vitro colony formation in the presence of the antibiotic G418 or 9-xylofuranosyladenine plus deoxycoformycin, respectively . Isoenzyme analysis also showed human ADA expression in the cultured mouse bone marrow. Biochim Biophys Acta, 1986 Jul 24, 859(2), 125 - 34 Action of calcium channel and beta-adrenergic blocking agents in bilayer lipid membranes; Shi B et al.; The action of beta-adrenergic blockers (propranolol, exprenolol, metoprolol, sotalol, atenolol, timolol) and calcium-channel blockers (verapamil, diltiazem) on the electrical properties and fluidity of bilayer lipid membranes (BLM and liposomes) has been investigated . When antibiotic ionophore substances were used as a probe, the electrical measurements showed that many of the drugs inhibited the cation transport across the membrane facilitated by the mobile carrier valinomycin, while having no significant effect on the cation transport through channels formed by gramicidin . The ability of the drugs to decrease the carrier-dependent membrane conductance was correlated to their partition into the lipid bilayer and the magnitude of transmembrane potential induced by them . In the TEMPO ESR spectral measurements, a number of beta-adrenergic and calcium blockers showed the fluidizing effect on liposomes composed of different lipids . The drug concentration required for a detectable change in TEMPO spectra parameter (f) was rather high (0.01 M verapamil), and the variation of pH from 6.5 to 3.0 did not affect the fluidizing effect of the drugs. Cancer, 1986 Jul 15, 58(2 Suppl), 573 - 83 Targeted drug delivery; Freeman AI et al.; Cancer chemotherapy drugs are neither specific, i.e., they do not act exclusively on the metabolic pathways of cancer cells, nor are they targeted solely toward cancer cells . However, recent research has begun to address, in part, the latter issue . Improved delivery of chemotherapeutic agents to tumor tissue in man appears to be an achievable goal in the next decade . Improved drug delivery includes developing predictive models that allow for laboratory assessment of the best treatment for a patient's cancer without exposing the patient to an empirical trial or to the possible morbidity from exposure to a less useful drug, or to the loss of time in the fight against cancer because of ineffectual therapy . Monoclonal antibodies directed against tumor-associated antigens have the potential to achieve major advances in targeted drug delivery . Monoclonal antibodies may have direct antitumor effects, or they can be used as "homing devices" when attached to a payload and can guide diagnostic or therapeutic agents to the targeted tissues . Carrier systems of all types have become available; these include liposomes and polymeric compounds which can carry drugs, radionuclides, toxins, or other materials in a protected environment . These carriers can also be bound to monoclonal antibodies for possible targeted delivery . Pharmacological sanctuaries have been recognized as a problem in cancer treatment . The best known of these is the central nervous system (CNS) . Techniques to temporarily disrupt the blood-brain barrier are now appearing . Mechanisms to administer therapy directly into the CNS are also being reassessed . Implantable pumps and reservoirs have been used to treat selected organs or for regional perfusions . Other treatments that are regional in scope include administration directly into a cavity or into a tumor . Computerized implantable devices should play a major role in cancer therapy in the future, in pain control as well as antibiotic and hormone administration . In recent years, mathematical models have been developed that can more accurately predict drug distribution and metabolism in various tissues of the body . Such models point the way to more logical designs of chemotherapeutic administration . The expanded use of autologous bone marrow transplantation, along with improving techniques of "purging" the marrow of tumor cells before reinfusion can be anticipated . Pro-drugs are substances that must be biotransformed in vivo to exert their pharmacologic effect.(ABSTRACT TRUNCATED AT 400 WORDS) Dtsch Med Wochenschr, 1986 Jul 11, 111(28-29), 1113 - 4 {Meningitis following lumbar puncture}; von Muhlendahl KE; Two young children underwent lumbar puncture because of fever and convulsions . After CSF examination had initially yielded no pathological findings, both children developed purulent meningitis . Second puncture and start of antibiotic therapy had been delayed, since CSF re-examination had only been performed two days after the first puncture . The literature reports on 23 similar cases in children . Whenever the clinical course suggests meningitis, one should therefore not hesitate to carry out a second lumbar puncture, even if CSF examination had yielded no pathological findings a short time ago. Int J Artif Organs, 1986 Jul, 9(4), 247 - 50 The occurrence of fever during hemodialysis and hemofiltration . A comparative study; Schaefer K et al.; The occurrence of fever during various blood purification methods was evaluated in a retrospective study . It could be demonstrated, that patients treated chronically by conventional hemodialysis experience six times more febrile episodes than patients on chronic hemofiltration (4.84% versus 0.81%) . Since many of the increased temperatures could not be explained by conventional means, it has to be assumed that the treatment itself caused the fever, possibly activating the monocyte hormone interleukin 1 . It is of further note that there was no difference in the magnitude of the temperature due to septicaemia or to no obvious cause . This finding necessitates in our opinion an early antibiotic therapy in those cases where fever develops without clear explanation. Avian Dis, 1986 Jul-Sep, 30(3), 580 - 4 Effect of medicated feed on tracheal infection and population of Mycoplasma gallisepticum in chickens; Cummings TS et al.; Six-week-old broilers were fed 50 g tylosin/ton, 400 g chlortetracycline (CTC)/ton, or unmedicated feed and then challenged intratracheally with R strain Mycoplasma gallisepticum (MG) . Feed-grade antibiotic medication did not prevent infection, but medication did lower the number of isolations from treated birds compared with controls . Only tylosin significantly lowered MG counts in the trachea . The log10 ID50 of birds receiving tylosin, CTC, or unmedicated feed were 5.8, 4.4, and 2.9, respectively . Six-week-old leghorns were placed on the three diets described previously and challenged with the R strain of MG . Birds were sacrificed at various times up to 10 weeks postchallenge (PC) . Compared with the control diet, the tylosin-medicated diet significantly reduced the tracheal MG count from day 1 to 4 weeks PC, whereas the CTC-medicated diet significantly lowered the tracheal MG count only at 3 days PC . In all groups, the MG count gradually declined after 1 week PC; by 8 weeks PC it was essentially the same in all groups . It was concluded that continuous medication has the potential for reducing MG tracheal populations only during the initial phase of an outbreak. Monatsschr Kinderheilkd, 1986 Jul, 134(7), 475 - 7 {Congenital piriformo-thyroid fistula as a cause of recurrent suppurative thyroiditis}; Schlamp D et al.; A previously healthy five year old boy presented with suppurative, febrile thyroiditis of the left lobe with pronounced general and local signs of inflammation, normal thyroid function and lack of thyroid antibodies . Intravenous antibiotic therapy improved the condition quickly . Six and nine months later however recurrent left lobe thyroiditis occurred . Endoscopic examination showed an internal fistula from the left piriform sinus to the left thyroidal lobe which was cut out . The case report confirms previous communications, that recurrent suppurative thyroiditis is nearly always caused by a piriform sinus fistula, probably a fourth pharyngeal pouch remnant which can be cured surgically. J Surg Res, 1986 Jul, 41(1), 16 - 23 Incorporation of microporous Teflon tracheal prostheses in rabbits: evaluation of surgical aspects; Bottema JR et al.; Because tracheal prostheses made of nonporous silicone rubber develop granulation tissue at the anastomoses, we tested a prosthesis made of a microporous material (polytetrafluoroethylene, Teflon) to see whether this problem could be avoided and the prosthesis could be successfully incorporated (luminal side covered by connective tissue and epithelium) . At various times after implantation in the cervical trachea of rabbits, the prostheses were inspected macroscopically for obstruction of the prosthesis lumen (lumen reduced by one-third or more) and microscopically for incorporation and inflammatory reaction (concentration of inflammatory cells) of the prosthesis . The prosthesis was successfully incorporated within 2-4 weeks in most rabbits without granulation tissue at the anastomoses . Two complications were infection of the prosthesis before incorporation was completed and obstruction of the lumen in the center of the prosthesis by granulation tissue or a deformed prosthesis wall . Both problems can be overcome, the first by giving an appropriate antibiotic for a longer period and the second by making a stiffer prosthesis . Thus, the microporous Teflon prosthesis is potentially useful as a tracheal prosthesis in rabbits. J Reprod Med, 1986 Jul, 31(7), 625 - 8 Actinomycotic pelvic inflammatory disease simulating malignancy; Goodman HM et al.; The protean and indolent nature of pelvic actinomycosis combined with the rarity of the disease poses a diagnostic dilemma . Woody induration and pelvic fibrosis may be present to such a degree that a diagnosis of pelvic malignancy is entertained . Early diagnosis and aggressive antibiotic therapy prior to definitive surgical management, even in the face of extensive anatomic changes, may enable the surgeon to perform relatively conservative surgery, obviating the need for procedures usually reserved for malignant disease. Aviat Space Environ Med, 1986 Jul, 57(7), 664 - 6 Effect of hyperbaric oxygen on the blood: cerebrospinal fluid transfer of tobramycin; Kent TA et al.; The blood:cerebrospinal fluid (CSF) transfer of the aminoglycoside antibiotic, tobramycin (TOB) was assessed in rabbits . The CSF:blood ratio of TOB, 90 min after a subcutaneous injection, was approximately 1:100 as measured by an agar disc diffusion bioassay . Hyperbaric oxygen therapy at a pressure of 3 ATA caused a slight, non-significant, increase in this ratio, while high dose carbon dioxide, a treatment known to damage the blood:brain barrier, more than doubled this ratio . Thus, hyperbaric oxygen has no significant effect on CSF concentration of TOB in rabbits with intact meninges. J Foot Surg, 1986 Jul-Aug, 25(4), 311 - 4 Radionucleotide scanning in osteomyelitis; Sachs W et al.; Radionucleotide bone scanning can be an excellent adjunct to the standard radiograph and clinical findings in the diagnosis of osteomyelitis . Bone scans have the ability to detect osteomyelitis far in advance of the standard radiograph . The sequential use of technetium and gallium has been useful in differentiating cellulitis and osteomyelitis . Serial scanning with technetium and gallium may be used to monitor the response of osteomyelitis to antibiotic therapy. Fundam Appl Toxicol, 1986 Jul, 7(1), 126 - 31 Identification of a subgroup of Sprague-Dawley rats highly sensitive to drug-induced renal toxicity; Riviere JE et al.; Laboratory rats available from breeding facilities are usually assumed to be homogeneous populations within each strain; however, previous studies in our laboratory suggested that there may be a subgroup of Sprague-Dawley rats which are highly sensitive to aminoglycoside nephrotoxicity . The present study clearly identifies a subpopulation of Sprague-Dawley rats which was highly sensitive to nephrotoxicity from supratherapeutic doses (75 mg kg-1 day-1) of the aminoglycoside antibiotic gentamicin . Gentamicin was administered subcutaneously in a divided regimen, 25 mg/kg every 8 hr, for 7 days . Statistical analysis of post-treatment serum creatinine (SCR) and urea nitrogen (SUN) concentrations demonstrated two distinct populations: normally responding rats (SCR = 1.92 +/- 0.54 mg/dl, SUN = 71.5 +/- 18.4 mg/dl, N = 87) and highly sensitive rats (SCR = 4.10 +/- 0.83 mg/dl, SUN = 146.4 +/- 24.9 mg/dl, N = 12) (mean +/- SD) . Comparison of predosing blood and serum chemistries between these two populations revealed statistical differences only in initial serum osmolality, oxygen tension, and total protein . Since there is a subpopulation of humans which are at risk for developing aminoglycoside nephrotoxicity due to unknown host factors, these highly sensitive Sprague-Dawley rats may provide an animal model for investigating this human clinical problem. Biull Eksp Biol Med, 1986 Jul, 102(7), 92 - 4 {Stereological analysis of ultrastructural changes in cardiomyocytes during adriblastina-induced cardiomyopathy}; Nurmukhambetov AN et al.; Both single and graded administration of an anthracycline antibiotic adriablastine at a dose of 20 mg/kg to white rats have resulted in cardiomyocyte volume decrease, dystrophia and lysis of myofibrils, and reduction of mitochondrial surface density volume . Accumulations of myelin bodies of different configuration and diffuse myolysis were observed . Myelin bodies and diffuse myolysis of cardiomyocytes in adriablastine-induced cardiomyopathy are believed to be a morphological sign of lipid peroxidation. Gan To Kagaku Ryoho, 1986 Jul, 13(7), 2337 - 41 {Growth-inhibitory activity of minocycline on various tumor cell lines in vitro}; Inaba M et al.; In order to investigate the possible mechanism for the therapeutic efficacy of tetracycline antibiotics against malignant pleural effusion, the effect of minocycline (MC), one of this type of antibiotic, on in vitro growth of tumor cells was examined . As a result, it was found that MC caused complete growth inhibition of various tumor cell lines at concentration of 10-20 micrograms/ml, but this action was reversible, suggesting that considerably long exposure time would be needed for these drugs to kill the tumor cells in vivo at a relatively low concentration . On the other hand, when a relatively high concentration of 100 micrograms/ml was applied, MC induced irreversible inhibition of cell growth even if the exposure time was comparatively short . Since 4 human lung tumor cell lines examined exhibited high sensitivity to these antibiotics, it seems possible that their direct administration in the form of a high-concentration solution into the pleural cavity would result in a direct cytostatic effect on tumor cells in clinical therapy. Am J Surg, 1986 Jul, 152(1), 62 - 9 Options in the management of perforations of the esophagus; Brewer LA 3rd et al.; A study of 90 cases of esophageal perforation in the antibiotic era emphasizes individualized treatment and options of therapy based on a fundamental understanding of modifying pathophysiologic factors . If the patient is seen during the first 24 hours, surgical repair and irrigating tube drainage continue to be the treatment of choice in the thoracic and abdominal regions, with certain exceptions . The exceptions include small perforations proved by a thin media esophagram or esophagoscopy without pleural involvement or constitutional symptoms . Such patients may be treated nonoperatively, with gastric drainage, antibiotics, and parenteral alimentation . However, for large perforations with extensive contamination of the mediastinum and pleura, an esophageal exclusion operation may be life saving . In the cervical region, irrigating tube drainage may be just as effectual as repair and drainage . In patients seen after 24 hours, size of the perforation and the amount of mediastinopleural infection, rather than the time that has elapsed, dictate optimal treatment. Am J Surg, 1986 Jul, 152(1), 11 - 5 A 7 year experience with low anterior sigmoid resections using the EEA stapler; Trollope ML et al.; The EEA stapler was used in 205 patients over a 7 year period with 19 complications (9 percent) and 1 death (0.5 percent) . Meticulous attention to technique and familiarization with the EEA stapler are necessary to achieve such results . The use of mechanical and oral antibiotic bowel preparation, perioperative systemic antibiotics, povidone-iodine irrigation of the rectal ampulla, and meticulous surgical technique have combined to lower the complication rate of this procedure to a minimum . The EEA stapler has greatly improved the safety and ease of anterior sigmoid resections and now provides a frequent alternative to abdominoperineal resection in many patients with midrectal and even low rectal lesions. Am Fam Physician, 1986 Jul, 34(1), 77 - 9 Gonococcal dermatitis-arthritis syndrome; English JC et al.; Gonococcal dermatitis-arthritis syndrome should be a diagnostic consideration in an adolescent or a young adult presenting with a skin rash in association with joint pain and swelling . Cultures and/or gram-stained smears should be obtained . Patients usually respond rapidly to antibiotic therapy. Urology, 1986 Jul, 28(1), 31 - 5 Surgical treatment of reflux in neurologically impaired child; Evans RJ et al.; Ninety-three consecutive patients with neurologically impaired bladders were evaluated for vesicoureteral reflux . Of 22 patients found to have reflux, 3 had spontaneous remission of reflux, 8 were maintained on suppressive antibiotic therapy, and 11 required ureteral reimplantation . A total of 14 refluxing renal units underwent ureteroneocystostomies . Twelve of 14 have had no postoperative reflux . The remaining two renal units are now free of reflux following augmentation cystoplasty . The modified Hutch ureteroneocystostomy is particularly suited for use in patients with neuropathic bladders, in that no submucosal tunnel is necessary . The operative technique is described. Surg Gynecol Obstet, 1986 Jul, 163(1), 1 - 4 A prospective randomized study of moxalactam versus gentamicin and clindamycin in penetrating abdominal trauma; Kreis DJ Jr et al.; We conducted a randomized, prospective study of moxalactam versus gentamicin plus clindamycin in 42 patients with penetrating abdominal trauma . Patients were randomized to receive intravenously either 2 grams of moxalactam every 12 hours or 80 milligrams of gentamicin every eight hours and 600 milligrams of clindamycin every six hours . Antibiotics were administered preoperatively and continued for a minimum of five days if hollow viscus injury occurred . For those without hollow viscus injury, only those patients receiving a minimum of three days of antibiotics were evaluated . A single intramuscular dose of 10 milligrams of vitamin K was also administered to all patients in the moxalactam group . There were 39 males and three females with a mean age of 33 years . Twenty patients received moxalactam and 22 received gentamicin plus clindamycin . The mechanism of injury was gunshot wound in 32 patients and stab wounds in ten patients . Eight patients in each group sustained injuries to the small intestine or colon, or both . The mean injury severity score was 22.6 and 21.2 in the single and double antibiotic regimen, respectively . The mean duration of antibiotic therapy was 5.8 and 7.0 days in the single and double antibiotic group, respectively . No infectious complications occurred in the moxalactam group whereas five infections occurred in four patients in the gentamicin plus clindamycin group (p less than 0.05) . These infections included one intra-abdominal abscess, two wound infections and two episodes of necrotizing fasciitis of the wound and abdominal wall . There were no complications attributable to moxalactam therapy . The over-all mortality rate was zero per cent . The total pharmacy cost of a five day course of moxalactam plus a single dose of vitamin K is $204.67 compared with $226.00 for a similar course of gentamicin plus clindamycin . We conclude that: moxalactam is at least, if not more, effective in preventing infectious complications after penetrating abdominal trauma compared with gentamicin plus clindamycin; moxalactam is safe in the doses used when combined with vitamin K, and 3, moxalactam is more cost-effective than gentamicin plus clindamycin dual antibiotic therapy. Yale J Biol Med, 1986 Jul-Aug, 59(4), 395 - 401 Risk of infection following penetrating abdominal trauma: a selective review; Rush DS et al.; Post-operative infectious complications following penetrating abdominal trauma are a major cause of morbidity and contribute significantly to increased length of hospitalization and costs of patient care . Our recent study suggests the individual patient's probability of major infection following traumatic intestinal perforation is high and can be predicted from risk factors identified at the time of surgery . The determinant of primary importance for development of infection confirmed by this study is peritoneal contamination by intestinal contents . Other significant risk factors (p less than 0.05) were number of organs injured, number of units of blood administered, ostomy formation for left colon injury, and the patient's age . Risk of infection can be calculated from these data and could potentially be used to guide post-operative decisions . Areas of trauma care in which alteration of therapy might result in significant savings include choice of antibiotics, duration of antibiotic administration, and wound management . This study supports the use of standardized operative procedures and parenteral antibiotics effective against endogenous aerobic and anaerobic organisms . If such observations continue to be supported by further randomized prospective studies, there is tremendous potential to further tailor surgical management for the individual patient in a more cost-effective manner. Arch Intern Med, 1986 Jul, 146(7), 1397 - 9 Hypoprothrombinemia in patients with cancer receiving cefoperazone and mezlocillin; Jones PG et al.; Forty-one patients with cancer who were receiving cefoperazone sodium plus mezlocillin sodium were prospectively followed up for the development of abnormal bleeding or hypoprothrombinemia . Ten of 41 patients developed an increased prothrombin time, three with a hemorrhagic episode . Serum transport proteins and serum carotene were measured in 18 patients, six of whom developed hypoprothrombinemia . Low serum prealbumin and low serum carotene levels were associated with the development of hypoprothrombinemia . Patients with cancer are especially predisposed to the development of antibiotic-associated hypoprothrombinemia . This is probably a result of protein-calorie malnutrition and low vitamin K stores. Jpn J Antibiot, 1986 Jul, 39(7), 1733 - 44 {Clinical evaluation of imipenem/cilastatin sodium in the pediatric field}; Hirosawa H et al.; Imipenem/cilastatin sodium (MK-0787/MK-0791) was evaluated for its safety and efficacy in 7 pediatric patients with infections . The clinical efficacy ratio was 100 percent . No side effect was observed except for elevations of S-GOT and S-GPT and eosinophilia in 1 patient . It may be considered that MK-0787/MK-0791 is a safe and useful antibiotic for the treatment of pediatric infections. Proc Natl Acad Sci U S A, 1986 Jul, 83(13), 4636 - 40 Identification of processing events in the synthesis of platelet-derived growth factor-like proteins by human osteosarcoma cells; Graves DT et al.; The human osteosarcoma-derived cell line U-2 OS expresses c-sis mRNA and synthesizes platelet-derived growth factor (PDGF)-like proteins . Pulse-chase experiments indicate that proteins of 23 kDa and 180 kDa are synthesized first . The 23-kDa protein undergoes dimerization and proteolysis, giving rise to the 30-kDa dimeric protein secreted by the cells . The 180-kDa protein is proteolytically cleaved in a complex series of steps that give rise to several intracellular species . It is also the likely precursor of high molecular mass PDGF-like or PDGF-associated proteins secreted by these cells . The processing and secretion of the 180-kDa protein is slower than that of the 23-kDa protein . Subcellular fractionation and studies with the antibiotic monensin indicate that the processing events occur in the Golgi-endoplasmic reticulum compartment of U-2 OS cells. Cancer Treat Rep, 1986 Jul, 70(7), 835 - 41 Pharmacokinetics of aclarubicin and its metabolites in humans and their disposition in blood cells; Ando S et al.; The pharmacokinetics of aclarubicin, a new anthracycline antibiotic, was studied in five patients with acute leukemia or in L1210 cell suspension . Aclarubicin disappeared very rapidly from plasma and whole blood after administration at a dose of 20 mg per patient by iv bolus injection . The concentration of active metabolite M1, on the other hand, increased for up to 2 or 4 hrs after administration and exceeded that of aclarubicin, and then remained at much higher concentrations than aclarubicin for up to 24 hrs after administration . In addition, the levels of aclarubicin and its metabolites in whole blood were much higher than the corresponding plasma levels in four of the patients . The drug concentrations in blood cells of 11 patients determined 4 hrs after administration showed a significant positive correlation with leukocyte counts . Moreover, the concentration of aclarubicin and its metabolites was found to be much higher in the leukocyte fraction than in the erythrocyte fraction in vivo and in vitro . These findings indicate that aclarubicin and its metabolites in blood cells were mainly accumulated in leukocytes . In the study of intracellular drug distribution in L1210 cells, the largest amount of aclarubicin was incorporated into the nuclear fraction . This suggests a close relationship between the pronounced drug accumulation in leukocytes and the high affinity of aclarubicin for DNA. Chem Biol Interact, 1986 Jul-Aug, 59(1), 55 - 72 The binding of CC-1065 to thymidine and deoxyadenosine oligonucleotides and to poly(dA).poly(dT); Krueger WC et al.; In this work, we report on the binding of the novel antitumor agent CC-1065 to poly(dA).poly(dT) and to mixtures of dA and dT oligomers as determined by electronic absorption and circular dichroism (CD) methods . In addition, the DNA binding properties of CC-1065 and its binding mechanism are compared to those of netropsin . CC-1065 binds to the polymer by at least three mechanisms to produce one irreversibly and two reversibly bound species . One reversibly bound species is moderately stable, but in time (days), it converts to the irreversibly bound species . Both of these species bind within the minor groove of the polymer and exhibit intense CC-1065 induced CD spectra . The other reversibly bound species does not acquire an induced CD . CC-1065 forces B-form duplex formation between mixtures of single strand dA and dT oligomers and binds irreversibly to the duplexes without showing the presence of an intermediate, reversibly bound species . The induced CD increases with increasing length of the oligomer, from the 5-mer (barely detectable CD) to the 14-mer (intense CD) . The 7-, 10- and 14-mer mixtures bind about 1, between 1 and 2, and between 2 and 3 CC-1065 molecules, respectively . Computer graphic models of the CC-1065-DNA complex show that the covalent adduct of CC-1065 and unreacted CC-1065 can attain the same close van der Waals contacts between adenine C2 hydrogens and antibiotic CH groups that were observed in the crystal structure of the netropsin-DNA complex . These contacts may account for the dA-dT base pair binding specificity of CC-1065 and for the stability of the reversibly bound CC-1065 species. Antimicrob Agents Chemother, 1986 Jul, 30(1), 147 - 51 Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli; Ubbink-Kok T et al.; The anthraquinones emodin (1,3,delta-trihydroxy-6-methylanthraquinone) and emodinanthrone (1,3,8-trihydroxy-6-methylanthrone) inhibited respiration-driven solute transport at micromolar concentrations in membrane vesicles of Escherichia coli . This inhibition was enhanced by Ca ions . The inhibitory action on solute transport is caused by inhibition of electron flow in the respiratory chain, most likely at the level between ubiquinone and cytochrome b, and by dissipation of the proton motive force . The uncoupling action was confirmed by studies on the proton motive force in beef heart cytochrome oxidase proteoliposomes . These two effects on energy transduction in cytoplasmic membranes explain the antibiotic properties of emodin and emodinanthrone. In Vitro Cell Dev Biol, 1986 Jul, 22(7), 381 - 6 Inherent resistance of HeLa cell derivatives to paromomycin; Bunn CL et al.; The human tumor-derived cell line HeLa S3 and nuclear and mitochondrial gene mutants derived from it are resistant to the aminoglycoside antibiotic, paromomycin (PAR) . Other carcinoma-derived cells, SV40-transformed cells, and four human diploid fibroblast cell lines are all sensitive to PAR . Sensitivity is dependent on cell density, and at cell numbers greater than 400/cm2 sensitive cells will proliferate in PAR . The resistance to PAR is inherited in a dominant manner in cell-to-cell fusion hybrids, but is not transferred in cytoplast-to-cell fusions . PAR resistance is therefore encoded by a nuclear gene(s) . Resistance to PAR is not caused by changes in the response of mitochondrial or cytoplasmic protein synthesis to PAR in vitro . The uptake of PAR is similar in resistant and sensitive cells, and dimethyl sulfoxide does not render resistant cells more sensitive . Thus, HeLa cell PAR resistance is unlike previously reported ribosomal mutations and may derive from differences in the intracellular metabolism of PAR. Proc Natl Acad Sci U S A, 1986 Jul, 83(13), 4617 - 21 GTPase center of elongation factor Tu is activated by occupation of the second tRNA binding site; Van Noort JM et al.; Interaction of the elongation factor EF-Tu with the antibiotic kirromycin results in activation of the GTPase center of the factor and in induction of an additional tRNA binding site (tRNA binding site II to distinguish it from the classical tRNA binding site I) . Activation of the GTPase center under these conditions is stimulated by addition of tRNA . Two-fold evidence is presented that this stimulation is due to tRNA binding to site II rather than to site I . First, a strong correlation is observed between stimulation of the GTPase activity and enhancement of the reactivity of Cys-81 of EF-Tu toward N-ethylmaleimide at various concentrations of aminoacyl-tRNA, deacylated tRNA, and N-acetylaminoacyl-tRNA . The latter effects signal tRNA binding to site II . Stimulation of the kirromycin-induced GTPase activity by tRNA binding to the factor also occurs when binding to site I is completely abolished . Such an abolishment was achieved by treating EF-Tu extensively with the thiol reagent L-1-tosylamido-2-phenylethyl chloromethyl ketone . EF-Tu X GTP thus treated has lost its ability to protect the ester bond of aminoacyl-tRNA . The relevance of these data for the sequence of events during protein synthesis and for control of translational fidelity is discussed. J Gen Virol, 1986 Jul, 67 ( Pt 7), 1361 - 71 The myeloproliferative sarcoma virus retains transforming functions after introduction of a dominant selectable marker gene; Ostertag W et al.; The dominant neomycin resistance gene (neoR) was introduced into the genome of the myeloproliferative sarcoma virus (MPSV), a replication-defective retrovirus carrying the mos oncogene . The resulting selectable neoR-MPSV virus did not lose its acute transforming property, unlike the results of attempts by other groups to insert marker genes into oncogenic viruses . NeoR-MPSV DNA was used to generate infectious virus by transfection followed by rescue with Friend or Moloney murine leukaemia virus . Infection of fibroblasts with this virus resulted in morphologically transformed cells which were resistant to the neomycin analogue G418 . Segregation of the two functions (transformation and G418 resistance) was not observed in more than 500 independent viral transfers to fibroblasts . Furthermore, neoR-MPSV retained the leukaemogenesis-inducing properties of the wild-type virus . Myeloproliferation and G418-resistance transfer did not segregate after passage in mice. Am J Med, 1986 Jun 30, 80(6B), 228 - 33 Cost-effective aminoglycoside therapy in surgical patients; Gladen HE; There is a risk that the current pressures for hospital cost containment may result in inappropriately restrictive administrative measures . A failure to take into account all factors in estimating the cost of antibiotic therapy yields a greatly distorted view of the importance of acquisition costs . Higher-priced drugs may actually be more cost-effective if they have greater efficacy, wider therapeutic range, and/or are less costly to prepare and administer . Simple microcomputer modeling techniques may be easily employed to examine the economic consequences of therapeutic decisions. JAMA, 1986 Jun 27, 255(24), 3394 - 6 Lyme disease during pregnancy; Markowitz LE et al.; Lyme disease is an increasingly recognized tick-borne illness caused by a spirochete, Borrelia burgdorferi . Because the etiologic agent of Lyme disease is a spirochete, there has been concern about the effect of maternal Lyme disease on pregnancy outcome . We reviewed cases of Lyme disease in pregnant women who were identified before knowledge of the pregnancy outcomes . Nineteen cases were identified with onset between 1976 and 1984 . Eight of the women were affected during the first trimester, seven during the second trimester, and two during the third trimester; in two, the trimester of onset was unknown . Thirteen received appropriate antibiotic therapy for Lyme disease . Of the 19 pregnancies, five had adverse outcomes, including syndactyly, cortical blindness, intrauterine fetal death, prematurity, and rash in the newborn . Adverse outcomes occurred in cases with infection during each of the trimesters . Although B burgdorferi could not be implicated directly in any of the adverse outcomes, the frequency of such outcomes warrants further surveillance and studies of pregnant women with Lyme disease. Minerva Med, 1986 Jun 23, 77(26), 1249 - 54 {Role of total parenteral nutrition (TPN) in the treatment of pseudomembranous colitis in surgical patients . Our experience}; Levis P et al.; The authors describe their experience using TPN (total parenteral nutrition) associated with specific drugs in the treatment of antibiotic-associated pseudomembranous colitis in surgical patients . They discuss the benefits and the possible complications of the above mentioned treatment . Three different cases observed during a three year period are reported; one of these is carefully analysed in order to better explain the methods and procedures used during TPN. Toxicol Appl Pharmacol, 1986 Jun 15, 84(1), 84 - 92 Mechanism of toxicity of 2,2,2-trifluoroethanol in rats; Fraser JM et al.; 2,2,2-Trifluoroethanol (TFE) is the toxic metabolite of the anesthetic agent fluroxene . TFE treatment (0.21 g/kg, ip) of male Wistar rats significantly reduced peripheral white blood cell count, bone marrow nucleated cellularity, and dry weight of the small intestine . These toxic effects of TFE were first observed at 8 to 16 hr after treatment, persisted for 96 hr, and were accompanied by severe diarrhea and edema of the small intestine . A non-lethal dose of TFE increased the sensitivity of rats to bacterial endotoxin lethality by approximately 1000-fold . Antibiotic and antiendotoxin pretreatment reduced the lethality of TFE from 80 to 20% of the rats, but did not prevent the other toxic effects of TFE . In vitro experiments with serum from TFE-pretreated rats (0.13 g/kg) supported the growth of an average of 65% fewer cultured bone marrow cell colonies compared to the number of colonies produced when serum from control rats was used . This suggests that TFE-induced bone marrow depression and leukopenia are related to a decrease in colony stimulating factor activity . Taken together these results explain the rapid development of lethal bacterial infections in TFE-treated rats . TFE-mediated damage to the small intestine combined with prolonged leukopenia decreases the resistance of the rat to endogenous pathogens leading to systemic bacterial infection . In addition, the increased sensitivity to endotoxin induced by TFE leads to lethal endotoxemia. Nucleic Acids Res, 1986 Jun 11, 14(11), 4617 - 24 Expression in mammalian cells of a gene from Streptomyces alboniger conferring puromycin resistance; Vara JA et al.; The gene encoding a puromycin N-acetyl transferase from Streptomyces alboniger has been cloned next to the SV40 early promoter in a mammalian cells-Escherichia coli shuttle vector . When this construction was introduced into VERO cells it expressed the relevant enzymic activity . Moreover, the puromycin N-acetyl transferase gene has been used as a dominant marker for the selection of transformed mammalian cells able to grow in the presence of the antibiotic. Jpn J Antibiot, 1986 Jun, 39(6), 1480 - 6 {Pharmacokinetics of astromicin intravenous drip infusion in patients with renal disorders}; Moriguchi R et al.; Astromicin (ASTM), a new aminoglycoside antibiotic, was administered to 7 patients with renal disorders . Concentrations of ASTM in blood were determined for pharmacokinetic analysis . ASTM was administered by intravenous drip infusion over 1 hour at a dose of 200 mg to each of 6 patients and at a dose of 100 mg to 1 patient . Renal function was observed by the clearance of intrinsic creatinine (Ccr) as the indicator . Concentrations of ASTM in blood became higher and retention times longer as degrees of the loss of renal function were larger . Although ASTM is proved to be one of drugs with the highest degree of safety compared with other existing aminoglycoside antibiotics, it should be administered with care to patients with renal disorders. In Vitro Cell Dev Biol, 1986 Jun, 22(6), 317 - 9 Optimal parameters for the polybrene-induced DNA transfection of diploid human fibroblasts; Morgan TL et al.; Recently it has been shown that Polybrene, in conjunction with dimethyl sulfoxide (DMSO) shock, can markedly increase frequency of DNA transfection of chicken embryo fibroblasts as compared with the frequency obtained with the standard calcium phosphate protocol . We have adapted this procedure for use with diploid human fibroblasts . Using plasmid DNA containing a dominant selectable marker gene (resistance to Geneticin), we have determined that treatment of the cells for 6 h in culture medium containing Polybrene at a concentration of 2 to 5 micrograms/ml, followed by a 4-min shock with 30% DMSO, resulted in the highest yield of transfectants, ca . 400/10(6) cells treated with as little as 100 ng of plasmid DNA . The selective agent could be added immediately after the DMSO shock . This allows transfection and selection to be carried out in the same dishes and ensures that each clone represents a unique event. J Hand Surg {Br}, 1986 Jun, 11(2), 271 - 3 Mycotic aneurysms of the upper extremity, report of two cases; Ho PK et al.; Two cases of mycotic aneurysm of the brachial artery secondary to illicit drug injection are described . Review of the literature shows an increased incidence of mycotic aneurysms secondary to intravenous/intra-arterial drug injections . There is a greater propensity for these aneurysms to rupture, thus early diagnosis and adequate antibiotic and surgical treatment is advised . Resection of the aneurysm and ligation of the vessel is the procedure of choice if adequate distal circulation exists. Antibiot Med Biotekhnol, 1986 Jun, 31(6), 445 - 9 {Modelling of rifampicin pharmacokinetics in experimental animals administered the drug intravenously and internally}; Firsov AA et al.; Pharmacokinetics of rifampicin on its single intravenous and oral administration to rats in doses of 25 and 50 mg/kg and on its intravenous administration to dogs in doses of 8 and 25 mg/kg was studied . When the antibiotic was administered intravenously to the animals, its pharmacokinetics was nonlinear . The linearity distortion in the rats was lower than in the dogs . However, the pharmacokinetic data relevant to the antibiotic administration in the above doses were satisfactorily described by the biexponential equation . The absolute extent of rifampicin systemic absorption following oral administration to the rats was 60 to 85 per cent . Tissue availability of the antibiotic on its intravenous administration was lower than that on its oral administration. Ophthalmology, 1986 Jun, 93(6), 757 - 62 Epidemiology of chlamydial eye diseases in a mixed rural/urban population of West Germany; Bialasiewicz AA et al.; 4260 conjunctival specimens of 2850 outpatients with keratoconjunctivitis of presumed infectious etiology were studied . Two thousand six hundred sixty-eight specimens (63%) revealed growth of bacteria, and 80 (2%) growth of fungi . One hundred ninety-nine specimens (5%) were McCoy cell culture or direct stain (monoclonal antibody or Giemsa) positive for Chlamydia trachomatis . two patients had a C . psittaci infection (ELISA techniques) . In patients with keratoconjunctivitis of bacterial etiology, overall incidence of McCoy cell culture-proven chlamydial infections was 7%; in the 20 to 30-year age group it was 12.5% . Simultaneous infections of chlamydiae and other bacteria were seen in 34 patients . Since sensitive and specific tests to diagnose chlamydial infections are available, ophthalmologists may be able to prevent these infections by agent-specific antibiotic therapy. Mol Biochem Parasitol, 1986 Jun, 19(3), 223 - 9 Inhibition of glyceraldehyde-3-phosphate dehydrogenase by pentalenolactone in Trypanosoma brucei; Duszenko M et al.; Pentalenolactone (PL), an antibiotic produced by several strains of Streptomycetes, is a specific irreversible inhibitor of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) . The effect of this antibiotic was studied in Trypanosoma brucei . In infected mice, due to the rapid metabolic inactivation of PL in vivo, trypanosomes were not affected by concentrations that were lethal to the host . Bloodstream trypanosomes in vitro were killed by low concentrations of PL (1.5 microgram ml-1), suggesting that there is no alternative to the glycolytic pathway for the generation of ATP in the bloodstream forms . In contrast, even high concentrations of PL (75 micrograms ml-1) were unable to inhibit growth of the procyclic form in vitro, presumably due to their ability to generate ATP independently of the glycolytic pathway. J Antibiot (Tokyo), 1986 Jun, 39(6), 827 - 32 Acetylation of blasticidin S by its producing actinomycetes; Sugiyama M et al.; A blasticidin S-producing actinomycetes, Streptoverticillium sp . JCM 4673 possesses an enzyme activity which acetylates the drug in the presence of acetyl coenzyme A . The modified drug was biologically inactive when tested against protein synthesis in vivo and in vitro . Production of the enzyme which acetylates blasticidin S increases with formation of the antibiotic during cell growth. J Antibiot (Tokyo), 1986 Jun, 39(6), 804 - 12 Clavines as antitumor agents, 3: Cytostatic activity and structure/activity relationships of 1-alkyl agroclavines and 6-alkyl 6-noragroclavines; Eich E et al.; The cytostatic potential of twenty antibiotic agroclavines has been examined in the L5178y mouse lymphoma cell system . Twelve of these compounds are described for the first time . It is shown that the substituent at N-1 of agroclavine is very important whereas the substituent at N-6 is of less influence if it is not hydrogen . Incorporation studies in the presence of 1-propylagroclavine suggest that DNA synthesis in the lymphoma cells is inhibited . The effect on the corresponding {3H}thymidine incorporation in murine spleen lymphocytes is comparably low . Neither a significant change of mRNA efflux nor of DNA polymerase alpha and beta activities was caused . The mechanism of action seems to be a fundamentally new one for ergoline compounds as interactions with alpha-adrenoceptors, dopamine and 5-hydroxytryptamine receptors are not involved. Am J Clin Oncol, 1986 Jun, 9(3), 189 - 91 Phase II trial of acivicin in patients with advanced colorectal carcinoma; Adolphson CC et al.; Acivicin, an amino acid antibiotic, was administered to 36 adult patients with previously treated metastatic colorectal cancer . The starting dose for good-risk patients was 15 mg/m2/day day given as a short intravenous infusion on 5 consecutive days every 3 weeks . Patients previously treated with radiation therapy, mitomycin, or nitrosoureas and those with inadequate bone marrow reserve received 12 mg/m2 on the same schedule . In 33 evaluable patients, one partial response occurred . Sixteen patients had stable disease with a median time to disease progression of 15 weeks (range 9-27) and a median survival of 8 months . The median survival of the whole group was, however, less than 6 months . Myelotoxicity was mild and resulted in no significant complications . Nonhematological toxicity primarily consisted of nausea, vomiting, drowsiness, depression, and altered mentation . Acivicin given by this schedule is inactive at these dose levels in previously treated patients with colorectal carcinoma. J Pediatr Surg, 1986 Jun, 21(6), 506 - 10 The avoidable excesses in the management of perforated appendicitis in children; Karp MP et al.; During a five-year period from 1979 to 1985, 100 consecutive children with perforated appendicitis were managed at our institution . These patients were divided into two groups, which were determined by length of illness and physical findings . Group A consisted of 88 children with signs and symptoms of peritonitis from appendiceal perforation . They were treated with fluid resuscitation, antipyretics, and triple antibiotics (ampicillin, gentamicin, clindamycin), and appendectomy within a few hours of hospitalization . Saline lavage was used . Group B was composed of 12 patients with a periappendiceal mass without generalized peritonitis who had symptoms of 6 to 12 days duration . They were treated nonoperatively with triple antibiotics and underwent interval appendectomy 4 to 6 weeks later . The complication rate for Group A was 6.8% . This included three wound infections (3.4%), one intra-abdominal abscess (1.1%), one patient with pneumonia and ileus (1.1%), and a small bowel obstruction (1.1%) . These results are equivalent to the lowest complication rate reported in the literature, in which the treatment included transperitoneal drainage, antibiotic lavage, and parenteral antibiotics . Group B patients had a 16.7% complication rate, which included one small bowel obstruction and one recurrent intra-abdominal abscess . Our method of management resulted in the lowest complication rate reported to date in children with perforated appendicitis . Transperitoneal drainage, delayed wound closure, and antibiotic lavage were not used . Subcuticular incisional closure resulted in minimal wound care and excellent cosmetic results . The experience demonstrates that with proper timing of surgery and appropriate use of contemporary antibiotics, the morbidity of perforated appendicitis can be limited and excesses of treatment can be avoided. Chemioterapia, 1986 Jun, 5(3), 208 - 12 Dialyzability of cefotaxime and mecillinam; el-Guinedy M et al.; The dialyzability of cefotaxime and mecillinam was studied in 20 patients with end-stage renal failure maintained on regular hemodialysis in the Ain Shams Dialysis Unit . Cefotaxime was found to be a dialyzable antibiotic with a hemodialysis clearance rate of 60.3 +/- 10.4 ml/min . Mecillinam was found to be more dialyzable, with a clearance rate of 118.8 +/- 14.4 ml/min. Clin Pharmacol Ther, 1986 Jun, 39(6), 654 - 9 Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion; Glynn AM et al.; The disposition of methylprednisolone was examined in six normal subjects after the injection of 20 mg iv methylprednisolone sodium succinate . Disposition studies were performed both without and with ketoconazole, 200 mg/day, for 6 days . Ketoconazole increased the methylprednisolone AUC and mean residence time (by 135% and 66%, respectively) and decreased clearance (60%), the terminal phase slope, and the volume of distribution . These findings are typical of macrolide antibiotic alteration of methylprednisolone disposition and consistent with reports of inhibition of drug metabolism by ketoconazole . Methylprednisolone reduced the 24-hour cortisol AUC by 44%, but morning cortisol concentrations returned to normal . Ketoconazole with methylprednisolone further reduced the 24-hour cortisol AUC and suppressed morning cortisol concentrations . Thus ketoconazole inhibits methylprednisolone disposition and extends the adrenal suppression effects of this corticosteroid. J Neurosurg, 1986 Jun, 64(6), 902 - 6 Risk factors for postoperative neurosurgical wound infection . A case-control study; Mollman HD et al.; A case-control analysis was performed to evaluate the association of 15 potential risk factors with postoperative infection in neurosurgical patients . All infections that developed postoperatively on the neurosurgical service at the University of Minnesota from January, 1970, to March, 1984, were identified . Among the 9202 operations performed during that time, 101 infections occurred for a rate of 1.1% . Three risk factors showed significant association with postoperative infection: cerebrospinal fluid (CSF) leak, concurrent noncentral nervous system (CNS) infection, and perioperative antibiotic therapy . The presence of a CSF leak and a concurrent non-CNS infection increased the estimated relative risk of infection to 13:1 and 6:1, respectively . The use of perioperative antibiotics was associated with a decrease in the risk of infection to approximately 20% of the control level . Three other risk factors (paranasal sinus entry, placement of a foreign body, and use of a postoperative drain) appeared to be associated with increased risk of infection, although statistical significance was not demonstrated . None of the remaining nine risk factors studied showed any suggestion of increased risk of infection. J Dairy Sci, 1986 Jun, 69(6), 1721 - 32 Management of dry cows to reduce mastitis; Eberhart RJ; The objective of mastitis control during the dry period is to have as few infected quarters as possible at calving . This depends on enhancing elimination of infections present at drying off and on reducing the new infection rate during the dry period; prevention of new infection appears to offer greater long-term benefits . Incidence of new infection is high in the dry period with periods of high susceptibility shortly after dry off and again prepartum . Pathogens of both contagious and environmental origin cause new dry period infections; however, exposure to contagious pathogens probably decreases with cessation of regular milking, whereas exposure to environmental pathogens continues throughout the dry period . Varying susceptibility over the dry period may be affected by bacterial loads on the teat skin, characteristics of the teat canal, and internal protective mechanisms . At present, antibiotic therapy at the end of lactation is the most effective means of eliminating existing infections and preventing new infections . Although there are reasons to prefer selective therapy, present evidence favors a recommendation for treatment of all cows at the time of drying off . A shortcoming of present therapy regimens for the dry period is that they provide little or no protective effect against new infection prepartum . Other mastitis control methods and management practices have not been shown conclusively to reduce new dry period infections . However, it appears that reduction of exposure to environmental pathogens during dry period should be recommended . More effective means to reduce new infections in the prepartum period are needed. J Pharm Sci, 1986 Jun, 75(6), 579 - 81 Polymerized phospholipid vesicles containing amphotericin B: evaluation of toxic and antifungal activities in vitro; Mehta R et al.; We have prepared lipid vesicles (liposomes) composed of polymerized bis{12-(methacryloyloxy)dodecanoyl}-L-alpha-phosphatidylcholine (DPL) which contain the antifungal polyene antibiotic amphotericin B (AMB) . It was necessary to devise a novel method for incorporating AMB into the liposomes subsequent to polymerization . The polymer liposome AMB was as effective as AMB in "conventional" liposomes in terms of inhibiting fungal growth in vitro . However, in contrast to "conventional" liposomes, the polymerized DPL vesicles did not protect mammalian cells against AMB induced toxicity. AJR Am J Roentgenol, 1986 Jun, 146(6), 1161 - 4 CT in the management of periappendiceal abscess; Barakos JA et al.; Abdominal CT was the primary diagnostic method used to evaluate 40 patients with suspected periappendiceal abscess . Its subsequent impact on patient management was then analyzed for several categories of clinical presentation, including patients with and without a palpable right-lower-quadrant mass and postoperative patients . CT was reliable in distinguishing periappendiceal abscesses from phlegmons; 17 of 18 patients with phlegmons responded promptly to antibiotic therapy alone without need for surgery . Patients with larger, poorly localized abscesses underwent early surgical drainage . CT was successful in guiding percutaneous catheter drainage (nine patients) or aspiration (one patient) of well-localized periappendiceal abscesses in 10 of 11 patients . One attempted catheter drainage guided by sonography was technically unsuccessful . In patients without a palpable right-lower-quadrant mass, CT was helpful in establishing the diagnosis of periappendiceal inflammation . However, there were three false-positive diagnoses in patients with pericecal fluid collections including a ruptured cecal lymphoma, a ruptured cecal diverticulum, and a ruptured corpus luteum cyst . A diagnostic approach with CT is presented in patients with suspected periappendiceal abscess. Jpn J Antibiot, 1986 Jun, 39(6), 1607 - 11 {Fundamental and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology}; Fujimoto H et al.; A new carbapenem antibiotic and renal dipeptidase inhibitor, imipenem/cilastatin sodium (MK-0787/MK-0791) were studied for the distribution into various tissues and for clinical aspects in obstetrical and gynecological fields . The following results were obtained . Concentrations of the drug in arterial blood, venous blood, and internal genital organs following an intravenous drip infusion were measured . The results demonstrated good transfer of the drug into various internal genital organs . Four patients with bacterial infections were treated with MK-0787/MK-0791 . Therapeutic results were good in 2 cases for, an effective rate of 50% . No side effects were noted in any cases . The above results suggested that MK-0787/MK-0791 may be a useful antibiotic for infectious diseases in the field of obstetrics and gynecology. Jpn J Antibiot, 1986 Jun, 39(6), 1601 - 6 {Fundamental and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology}; Horii T et al.; Fundamental and clinical studies of imipenem/cilastatin sodium (MK-0787/MK-0791), a new carbapenem antibiotic, were carried out . The results obtained were summarized below . At a dose of 500 mg/500 mg, the penetration of MK-0787/MK-0791 into internal genital organs was good . The penetration of MK-0787/MK-0791 into pelvic dead space exudate was also good . Clinical results obtained were good in 4 patients and poor in 1, with an efficacy rate of 80% . No side effects were observed, but 1 patient showed slight elevations of GOT, GPT, Al-P and LDH . From these results, MK-0787/MK-0791 appeared to be a useful drug for the treatment of various infections in the field of obstetrics and gynecology. Jpn J Antibiot, 1986 Jun, 39(6), 1526 - 30 {Fundamental and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology}; Okamura K et al.; Seven patients with gynecologic infections were treated with the new carbapenem class of antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791) at a dose level of 500 mg/500 mg or 250 mg/250 mg administered intravenously every 12 hours for 5 days . The results obtained were as follows . Clinical effects of MK-0787/MK-0791 were analyzed in 7 patients, including 1 case with pelvic peritonitis, 2 cases with endometritis, adnexitis and pelvic peritonitis, abdominal abscess, vaginal cuff infection and parametritis, and pyometra . Excellent clinical response was seen in 3 cases and good response in 4 cases . No side effect nor abnormal finding in clinical laboratory values was seen in all patients. Arch Mal Coeur Vaiss, 1986 Jun, 79(7), 1062 - 9 {Acute native endocarditis . The results of surgical treatment}; Jault F et al.; Between January 1978 and December 1984, 141 cases of acute native valve endocarditis were treated surgically in the Department of Thoracic and Cardiovascular Surgery of the Pitie Hospital . The diagnostic criteria of acute native valve endocarditis were the duration of treatment (antibiotic therapy for less than 40 days), the characteristic operative appearances of the lesions, and the results of anatomo-pathological examination of the excised valves . The infecting organism was not isolated in 35% of cases . The aortic valve was the commonest site of infection (65.2% with a high incidence of abscess of the aortic ring, irrespective of the causal organism . The operative mortality was 5.6% . This depended mainly on the preoperative haemodynamic status of the patient . The duration of antibiotic therapy prior to surgery did not seem to be relevant . The 3 years survival rate was 78% . The secondary reoperation rate was 7% . There was a higher incidence of secondary perivalvular regurgitation in patients who had previously had an abscess of the aortic ring. Mol Cell Biol, 1986 Jun, 6(6), 2198 - 206 Phenotypic change from transformed to normal induced by benzoquinonoid ansamycins accompanies inactivation of p60src in rat kidney cells infected with Rous sarcoma virus; Uehara Y et al.; Three benzenoid ansamycin antibiotics (herbimycin, macbecin, and geldanamycin) were found to reduce the intracellular phosphorylation of p60src at a permissive temperature (33 degrees C) in a rat kidney cell line infected with a temperature-sensitive mutant of Rous sarcoma virus . This effect was accompanied by morphological changes from the transformed to the normal phenotype . The filamentous staining pattern of actin fibers was observed in the cells treated with these antibiotics at 33 degrees C . Removal of the antibiotics allowed the cells to revert to the transformed morphology . Ansamitocin, another benzenoid ansamycin, and naphthalenoid ansamycins such as streptovaricin and rifamycins did not show this effect . Pulse-labeling of the antibiotic-treated cultures with 32Pi showed a marked reduction of 32P radioactivity incorporated into p60src . A parallel experiment with {35S}methionine showed that synthesis of p60src was slightly inhibited . The immune complex prepared by mixing the herbimycin-treated cell extracts with antibody against p60src was inactive in vitro in phosphorylating the complex itself . On the contrary, the immune complex derived from untreated cells was active in vitro even in the presence of the antibiotics . These results suggest that benzoquinonoid ansamycins have no direct effect on src kinase but destroy its intracellular environment, resulting in an irreversible alteration of p60src and loss of catalytic activity. Bioorg Khim, 1986 Jun, 12(6), 764 - 70 {Nucleotide sequences in DNA showing preferential binding with distamycin A and acridine derivatives}; Iashina LN et al.; The specificity of DNA X dye binding was studied . Antibiotic distamycin A was bound most strongly to the DNA sequences composed of three or more neighboring A X T pairs . Acrichin and 7-aminoacrichin proved to be weak specific inhibitors binding predominantly within the A X T regions. Biosci Rep, 1986 Jun, 6(6), 557 - 64 Effect of alkylation with streptozotocin on the secondary structure of DNA; Rizvi RY et al.; S1 nuclease hydrolysis and hydroxyapatite chromatography were used to study the effect of the alkylating antibiotic, streptozotocin, on the secondary structure of DNA . Native calf thymus DNA was alkylated in vitro with increasing concentrations of streptozotocin and subjected to S1 nuclease hydrolysis . An increasing degree of DNA degradation was seen, suggesting a destabilization of the secondary structure . Indirect evidence, deduced from alkaline hydrolysis, effect of NaCl on S1 nuclease hydrolysis, and hydroxyapatite chromatographic analysis of alkylated DNA, suggested a significant alkylation of DNA phosphates in addition to DNA bases . Nicotinamide has been reported to alter the cytotoxic and carcinogenic effects of streptozotocin . Our experiments indicate that in the presence of nicotinamide, streptozotocin causes the formation of a greater proportion of alkylated bases in relation to alkyl phosphotriesters . This may have significance in relation to the differential cytotoxicity of streptozotocin in the absence and presence of nicotinamide. J Chromatogr Sci, 1986 Jun, 24(6), 249 - 53 Analysis of various classes of drugs by capillary supercritical fluid chromatography; Later DW et al.; Three classes of drugs were screened for analysis feasibility by capillary column supercritical fluid chromatography . These included steroids, therapeutic antibiotic drugs, and drugs of abuse, such as cannabinoids . Supercritical fluid carbon dioxide was used as the mobile phase in conjunction with a methylpolysiloxane stationary phase capillary column and a flame ionization detector . All compounds considered were analyzed either as single component solutions, simple mixtures, or in actual complex mixtures. Arch Surg, 1986 Jun, 121(6), 641 - 8 Closure of abdominal incisions with subcutaneous catheters . A prospective randomized trial; Farnell MB et al.; A preliminary report from our institution suggested that closure of abdominal incisions with subcutaneous, closed-suction catheters intermittently irrigated with antibiotic resulted in decreased wound infection rates . To test this hypothesis, a prospective, randomized, controlled trial was undertaken to compare the results of primary closure, subcutaneous catheter irrigated with saline or antibiotic, and subcutaneous catheter alone . During the two-year trial, 3,282 incisions (type II, III, or IV) were analyzed . Subcutaneous catheter placement alone or with antibiotic or saline irrigation was not superior to primary closure for type II or III incisions . A trend favoring subcutaneous catheter and antibiotic irrigation was observed for type IV incisions . This finding suggests that further clinical trials designed to assess the role of subcutaneous catheter placement and antibiotic irrigation in decreasing wound infection rates are warranted in type IV incisions. Antibiot Med Biotekhnol, 1986 Jun, 31(6), 411 - 6 {Changes in the permeability of streptomycete cytoplasmic membranes due to gramicidin S and its derivatives}; Bulgakova VG et al.; Exposure of intact mycelium and protoplasts of Streptomyces sp . 26-115 to gramicidin S resulted in impairment of permeability of the cytoplasmic membranes thus inducing a loss of low molecular compounds by the cells and protoplasts . Aminoacyl and guanyl derivatives of gramicidin S with respect to the delta-amine group of ornithine were somewhat less effective with respect to the streptomycete membranes . The same as the initial antibiotic, these derivatives had positively charged groups . The changes in the membranes of the streptomycete protoplasts induced by gramicidin S and its derivatives did not result in the protoplast lysis accompanied by decreasing of the suspension optical density . The neutral derivative having no positive charge and not capable of complexing with the membrane phospholipids and the carboxyl-containing derivative with a negative charge showed a low membrane activity when applied to the protoplasts and induced no impairment of permeability of the intact mycelium membranes . The use of phosphates as factors increasing the membrane activity of the gramicidin derivatives having no positive charge is not possible since in the presence of phosphates streptomycete protoplasts are readily destroyed. Can J Microbiol, 1986 Jun, 32(6), 465 - 72 Purification and characterization of kynurenine formamidase activities from Streptomyces parvulus; Brown D et al.; Two forms of kynurenine formamidase (EC 3.5.1.9; aryl-formylamine amidohydrolase) are present in extracts of Streptomyces parvulus . The higher molecular weight enzyme (Mr = 42 000), kynurenine formamidase I, appears to be constitutive and is present at relatively constant but low levels in antibiotic producing and nonproducing cultures, whereas the synthesis of the lower molecular weight form (Mr = 25 000), kynurenine formamidase II, is initiated just prior to the onset of actinomycin formation . It is postulated (i) that kynurenine formamidase II catalyzes the second step in the pathway from tryptophan----actinocin, and (ii) that it is regulated specifically for the specialized function of actinomycin biosynthesis . The role of kynurenine formamidase I is unknown . Formamidase I and II activities were purified from extracts of S . parvulus and kinetic parameters of the two enzymes were determined . Although some of the properties of the two enzymes are quite similar (substrate specificities, Km values), some striking differences were noted (pH and temperature optima, molecular size, chromatographic properties, sensitivity to certain ions and chemicals) . Mutant studies suggest that expression of the gene(s) coding for formamidase II activity play an essential role in regulating the formation of actinocin and, hence, antibiotic synthesis . Kynurenine formamidase activity was also found in a representative number of Streptomyces species and related organisms suggesting that the enzyme may function in the degradative metabolism of tryptophan by certain actinomycetes in nature. Dtsch Med Wochenschr, 1986 May 30, 111(22), 847 - 53 {Ultrasound-guided fine-needle puncture in the diagnosis and therapy of liver and spleen abscesses}; Schwerk WB et al.; A total of 41 diagnostic and therapeutic fine-needle aspiration punctures were performed under ultrasound control in 28 patients with solitary or multiple abscesses of liver (26) or spleen (2) . Nonoperative measures (drainage-fine needle puncture, local and systemic antibiotics) cured 19 patients; in nine, primary surgical abscess drainage was performed . One operated patient with multiple liver abscesses died of generalized sepsis (mortality rate 3.6%) . All 14 hepatic or splenic abscesses in which percutaneous fine-needle drainage was performed, including local and systemic antibiotic administration, were treated successfully . In two of 41 fine-needle aspiration punctures bleeding complications were recorded but did not require any treatment . The method was reliable and effective in the definitive diagnosis and treatment of hepatic and splenic abscesses, with a lower complication and mortality rate than surgical drainage. J Biol Chem, 1986 May 25, 261(15), 6670 - 6 Fluorescence studies on a streptomycin-induced conformational change in ribosomes which correlates with misreading; Hanas JS et al.; The fluorescent reagent N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid (I-AEDANS) was employed to detect and study the previously reported conformational change in the Escherichia coli ribosome induced by streptomycin . Labeling of ribosomes with this probe, which results in the derivatization of proteins S18 and L31', described earlier, inhibits neither their ribosomal protein synthesizing nor misreading ability . To calculate the amount of streptomycin bound to the ribosome, we determined the K'D for streptomycin, which is 0.24 micron, indicating that under our conditions, bound streptomycin/ribosome molar ratios are low, not in excess of 1 . Under these conditions, streptomycin addition induces fluorescence quenching by 15% but does not affect streptomycin-resistant ribosomes . Maximal misreading occurs at these same ratios . Removal of AEDANS-L31' from the ribosomes drastically reduces streptomycin-induced quenching indicating the involvement of the environment of this protein in streptomycin action . The finding that streptomycin decreases AEDANS-L31' affinity for the ribosome supports this view . Streptomycin has been shown to bind to the 30 S subunit protein S4 while the 50 S protein L31' has been shown to be localized at the subunit interface . Thus, the observation that streptomycin influences this 50 S subunit protein L31', combined with the tight correlation between the effects of streptomycin on quenching and on misreading, strongly suggests that this antibiotic induces a conformational change at the subunit interface of the ribosome, and that this results in misreading . Polyuridylic acid also induces a conformational change in the ribosome but the polynucleotide and streptomycin seem to act independently . Streptomycin-resistant ribosomes, which undergo neither streptomycin-induced fluorescence nor streptomycin-induced misreading, are resistant to misreading induced by high Mg2+ as well. Biochem Biophys Res Commun, 1986 May 14, 136(3), 1001 - 6 The effects of polymyxin B, a protein kinase C inhibitor, on insulin secretion from intact and permeabilized islets of Langerhans; Stutchfield J et al.; Polymyxin B (0.01-1 mM), a polyamine antibiotic, inhibited both phorbol ester- and glucose-stimulated insulin secretion from isolated rat islets of Langerhans . This inhibition was rapidly reversible . Assay of the cytosolic protein kinase C by measurement of incorporation of labelled phosphate into a histone substrate demonstrated the presence of activity in islet extracts which could be stimulated by 12-O-tetradecanoylphorbol-13-acetate and inhibited by polymyxin B . These results suggest that protein kinase C plays a role in glucose-induced insulin secretion. Am J Emerg Med, 1986 May, 4(3), 214 - 7 Polyurethane and silver sulfadiazene dressings in treatment of partial-thickness burns and abrasions; Stair TO et al.; Epi-Lock, a 1-mm-thick semipermeable sheet of modified polyurethane dressing material, was compared with silver sulfadiazene cream (Silvadene) in a prospective, randomized, cross-over-controlled study in which 50 patients alternated changing antibiotic cream daily with leaving the polyurethane sheet in place for a week . Overall, patient and physician preference for Epi-Lock was statistically significant (P less than 0.004), based on less pain, easier care, and faster healing . The collection of fluid under the polyurethane dressing and the necessity of leaving the wound covered for a week were less well accepted . Epi-Lock represents a major advance in wound dressing materials and should eventually gain wide application in outpatient treatment of partial thickness burns and abrasions. Obstet Gynecol, 1986 May, 67(5), 652 - 6 Surgical management of diffuse peritonitis complicating obstetric/gynecologic infections; Rivlin ME et al.; A retrospective review of 176 women undergoing surgery for diffuse peritonitis secondary to pelvic infections from 1972 to 1976 was conducted . Mortality with septic abortion was 27.3% (12 of 44), with pelvic inflammatory disease 7.1% (eight of 113), and with puerperal sepsis 6.7% (one of 15) . Overall mortality was 13.1% (23 of 176) . Mortality was lower (P less than .05) with surgery within 24 hours (7.5%, six of 80) than after 24 hours (17.7%, 17 of 96) . Mortality was lower (P less than .01) with specific antianaerobic antibiotics (zero of 36) than without (16.4%, 23 of 140) . Mortality was 21.3% with hysterectomy (ten of 47) and 10.1% (13 of 129) with conservative surgery, however hysterectomy was usually performed in the more severe cases (septic abortion 75%, puerperal sepsis 66%, pelvic inflammatory disease 3%) . Mortality declined from 17.6% in 1972 to 1974 (21 of 119) to 3.5% in 1975 to 1976 (two of 57) . Significant differences between the two periods included an increased use of specific antianaerobic antibiotics (8.4%/45.5%) and an increased incidence of early surgery (35.3%/66.6%) in the latter years . This series emphasizes the overriding importance of early surgery and the need for the inclusion of specific antianaerobic antibiotic agents in the chemotherapeutic regimen. Biochem J, 1986 May 1, 235(3), 639 - 43 Characterization of three-fraction mycobacillin synthetase; Mukhopadhyay NK et al.; Mycobacillin synthetase lacks aspartic acid racemase, alanine racemase and glutamic acid racemase activities . The enzyme also does not respond to ATP-{32P}Pi exchange, nor does it catalyse the antibiotic synthesis in presence of amino acids of configuration opposite to that present in the molecule . Preincubation with optical isomers of opposite configuration inhibited the ATP-{32P}Pi exchange reaction to the extent of 60-90% . None of the three fractions of mycobacillin synthetase contained a pantothenic acid arm . Two molecules of ATP are required to synthesize one peptide bond of mycobacillin . Intermediate peptides of mycobacillin are not covalently linked to the three-fraction mycobacillin synthetase. J Reprod Med, 1986 May, 31(5), 339 - 42 Laparoscopic tubal sterilization combined with removal of an intrauterine contraceptive device . A report of 49 cases; Seiler JS; A retrospective study was done on 49 patients who underwent removal of an intrauterine device (IUD) and laparoscopic sterilization as a combined procedure during a 13-year period at Booth Memorial Medical Center, Flushing, New York . Five patients were given prophylactic antibiotic therapy, one was treated with postoperative antibiotic therapy for an asymptomatic actinomycosis infection of the endometrium, diagnosed on the curettings, and two patients developed postoperative infections requiring antibiotic therapy . Twenty-one patients had endometritis of various degrees diagnosed on the endometrial curettings, but only two developed clinical infections postoperatively . Elimination of those patients receiving prophylactic antibiotics from the study group left 43, of whom 41 (95%) had an uncomplicated postoperative course and did not develop clinical pelvic inflammatory disease even though 15 of them had endometritis diagnosed on curettage . It appears that removal of an IUD at the time of laparoscopic sterilization does not significantly affect the safety or postoperative morbidity of the sterilization procedure. Rev Fr Gynecol Obstet, 1986 May, 81(5), 283 - 5 {Vulvovaginitis in young girls}; Berlier P; What is required to cope with simple vulvitis in little girls is local hygeine and topical antibiotics, possibly associated with very mild estrogen therapy . In cases of gonococcus, systemic antibiotic medication is required. Antimicrob Agents Chemother, 1986 May, 29(5), 906 - 8 Penetration of ceftriaxone into human pleural fluid; Benoni G et al.; The pharmacokinetics of ceftriaxone were studied for seven patients with pleural effusion of various etiologies . All patients received 1 g of antibiotic, administered as an intravenous bolus . The pleural fluid had a high total protein content (6.0 g/dl) . Ceftriaxone levels in plasma and in pleural fluid were determined by the agar well diffusion technique . Total and free drug concentrations in pleural fluid reached 7 to 8.7 and 3.8 to 2.3 micrograms/ml, respectively, in 4 to 6 h . The disappearance of the drug from the pleural fluid was very slow . In these patients, therapeutic ceftriaxone levels were present for at least 53 h in pleural fluid. Antimicrob Agents Chemother, 1986 May, 29(5), 873 - 6 Pharmacokinetics of cefotaxime, moxalactam, and cefoperazone in the early puerperium; Charles D et al.; Twelve parturient women volunteered to receive 1 g of cefotaxime on the second or third day postpartum by intravenous infusion over 3 min . Blood was taken from the antecubital vein of the contralateral arm at 0.25, 0.5, 0.75, 1, 2, 4, and 6 h . The concentration of cefotaxime in serum was assayed by agar diffusion, with Sarcina lutea ATCC 9341 as the indicator strain . The same 12 women received an identical dose of antibiotic 4 months after the first dose, and blood was taken at the same time intervals as in the first study to measure antibiotic levels . An additional 24 women participated in identical studies with either moxalactam or cefoperazone . Cefoperazone afforded the highest concentration in serum of the three drugs, followed by moxalactam . These differences in the concentration in serum were seen both early postpartum and 4 months later . However, the concentration in serum of all three drugs was diminished 2 and 3 days postpartum compared with 4 months postpartum . Most pharmacokinetic parameters were also significantly altered early in the puerperium relative to those obtained 4 months later . The altered pharmacokinetic behavior of antibiotics associated with pregnancy appears to persist into the early puerperium. J Antimicrob Chemother, 1986 May, 17(5), 637 - 40 Comparative pharmacokinetics of cefamandole, cefuroxime and cephradine during total hip replacement; Davies AJ et al.; Serum, bone and tissue levels of the three cephalosporins, cefamandole, cefuroxime and cephradine were determined in 60 patients given a single 1 g dose intravenously before total hip surgery and two similar doses at 8 h intervals . The levels achieved were comparable for all three antibiotics, hence the choice of prophylactic antibiotic for total hip replacement should be guided by the pathogens causing infection and cost of the antibiotic. Br J Cancer, 1986 May, 53(5), 595 - 600 9-alkyl anthracyclines . Absence of cross-resistance to adriamycin in human and murine cell cultures; Scott CA et al.; Four cell lines of human (CCRF CEM and U266BL) or murine (L1210 and P388D1) origin, resistant to the anthracycline antibiotic Adriamycin (doxorubicin) were selected in vitro from cultured cells by serial passage in the presence of Adriamycin . The resistant sublines were also cross-resistant to Mitoxantrone, 4'-epi Adriamycin and a number of novel anthracyclines including 4'-deoxy and 4'-methoxy analogues . However, a series of 9-alkyl substituted 4-demethoxyanthracyclines retained full activity against all the resistant sublines as did Aclacinomycin A . These results suggest that 9-alkyl substitution of 4-demethoxy-anthracyclines is an important determinant of activity against Adriamycin-resistant cell lines in vitro. Am J Hosp Pharm, 1986 May, 43(5), 1210 - 3 Pharmacy initiatives to reduce clindamycin use; Greene SA et al.; The effectiveness of clinical pharmacists and attending physicians in altering the prescribing of metronidazole and clindamycin by resident physicians was evaluated, and the effect of these changes on antibiotic costs was determined . In July 1983, clinical pharmacists and attending physicians educated resident physicians about the efficacy and cost-effectiveness of substituting metronidazole for clindamycin in the treatment of intraabdominal and pelvic infections . A three-month educational program was implemented, which included distribution of a newsletter and involvement of clinical pharmacists in patient rounds . The use patterns of these drugs were then monitored for a 12-month period . A total of 425 treatment periods for 414 patients were reviewed, representing 91% of all therapy with metronidazole and clindamycin . Metronidazole use increased from 18.2% one month after implementation of the educational program to a plateau of 50% by November . Clindamycin expenditures decreased by more than 50% from the previous fiscal year, resulting in a savings of $33,469 to the pharmacy . The prescribing patterns of resident physicians were altered and cost savings were realized as a result of a comprehensive educational program that focused on substituting metronidazole for clindamycin . The program's success was enhanced because an equally efficacious agent was available and because of the participation of clinical pharmacists in patient rounds. Clin Radiol, 1986 May, 37(3), 235 - 8 The diagnosis of aortic root abscess by cross-sectional echocardiography; Mulcahy D et al.; Aortic root abscess is frequently a lethal complication of infective endocarditis . Early diagnosis of this complication is of paramount importance because antibiotic therapy is often ineffective and early surgery is probably the treatment of choice . We have compared the diagnostic accuracy of cross-sectional echocardiography with operative findings in the diagnosis of aortic root abscess . Aortic root abscess was diagnosed in nine of 129 patients with infective endocarditis at the National Heart Hospital between 1983 and 1985 . Cross-sectional echocardiography demonstrated the presence and location of the aortic root abscess in eight cases; in the ninth case a small abscess was missed . In two other cases, a large abscess was visualised, but abscesses of between 2 mm and 4 mm were missed; the extent and size of large aortic abscesses tended to be underestimated . Echocardiography should be an integral part of the investigation of patients with aortic valve infective endocarditis. Arch Phys Med Rehabil, 1986 May, 67(5), 314 - 8 Osteomyelitis associated with pressure ulcers; Thornhill-Joynes M et al.; Bone biopsies were performed in spinal cord injured patients with pressure ulcers in whom osteomyelitis was suspected . Roentogenograms and bone and gallium scans were also evaluated to determine their usefulness in diagnosing osteomyelitis . Infected bone underlying pressure ulcers revealed only mild focal inflammatory changes which did not correlate well with x-ray and nuclear scan abnormalities . Negative scans, however, essentially ruled out osteomyelitis . There was no clear association of delayed healing or recurrence of pressure sore with osteomyelitis . Antibiotic therapy of greater than three weeks' duration did not significantly affect the outcome of the disease. Am Rev Respir Dis, 1986 May, 133(5), 932 - 4 Recurrent Nocardia pneumonia in an adult with chronic granulomatous disease; Jonsson S et al.; The diagnosis of chronic granulomatous disease was made for the first time in a young adult when he presented with Nocardia asteroides pneumonia . Treatment with trimethoprim/sulfamethoxazole for 10 wk brought about an apparent cure of the infection . Two and one half years later N . asteroides pneumonia recurred and resulted in death from respiratory failure . Antibiotic susceptibility studies suggested that both episodes were caused by the same organism . This suggestion was supported by endonuclease restriction analysis, which showed that the plasmids from both Nocardia isolates were identical . Late recurrence of pneumonia caused by N . asteroides occurs only rarely . In this patient, recurrent infection appeared to be related to persistence of colonizing organisms in the host. Surgery, 1986 May, 99(5), 626 - 30 Successful management of hepatic abscesses by percutaneous catheter drainage in chronic granulomatous disease; Skibber JM et al.; Chronic granulomatous disease (CGD) is a disorder of polymorphonuclear leukocytes that can cause multiple recurrent hepatic abscesses in 40% of those patients with the disorder . The mortality rate from this complication of CGD is estimated at 27% . Treatment has consisted of extensive surgical debridement and drainage and prolonged antibiotic therapy; however, this approach is accompanied by high morbidity and the frequent need for reoperation . Successful percutaneous drainage of multiple hepatic abscesses in a patient who had previously undergone 10 operative procedures to manage hepatic abscesses is reported . With the development of imaging and percutaneous drainage techniques, as well as the recurrent nature of this problem, percutaneous management should be given consideration in appropriate patients with CGD with hepatic abscesses. Pathol Biol (Paris), 1986 May, 34(5), 332 - 8 {Experimental and clinical evaluation of the biliary elimination of ceftazidime}; Brogard JM et al.; After adding 10 mg of ceftazidime to the circulating blood of five isolated rabbit liver perfusions, total antibiotic excretion over a 3 hours period accounted for 1.4% of the administered dose; only 0.9% was found to be metabolized by the liver . In five healthy subjects given 2 g ceftazidime intravenously, 0.05% (102 +/- 576 micrograms) was recovered in the duodenal fluid over a four-hour period . In 10 patients with a T-tube inserted following cholecystectomy, 0.21% of a 2 g dose of ceftazidime injected intravenously was found in the bile collected over a 12-hour period (4 161 +/- 489 micrograms); a mean biliary peak of 36.3 +/- 4.0 micrograms/ml was recorded during the second hour . In 10 patients in whom serum, choledochal bile and gallbladder bile were sampled simultaneously during surgery 1 hour after IV administration of ceftazidime, the concentrations found were 40.6/e 2.1, 78.3 +/- 12.0 and 17.9 +/- 7.5 micrograms/ml respectively . Our results suggests that ceftazidime may be suitable in the treatment of biliary tract infections. Urologe A, 1986 May, 25(3), 153 - 6 {Significance and problems of Chlamydia detection in urologic patients}; Krech T et al.; Chlamydiae represent the aetiological agent in non-gonococcal urethritis in about 50% of the cases, but it is also increasingly recognized that Chlamydia trachomatis can cause prostatitis or epididymitis . The introduction of methods for the direct detection of chlamydia in clinical materials allows early diagnosis and therefore effective antibiotic therapy . The new tests however give both false positive and false negative results. J Biochem (Tokyo), 1986 May, 99(5), 1447 - 54 Effect of thiolactomycin on the individual enzymes of the fatty acid synthase system in Escherichia coli; Nishida I et al.; Thiolactomycin, an antibiotic with the structure of (4S)-(2E,5E)-2,4,6-trimethyl-3-hydroxy-2,5,7-octatriene-4-++ +thiolide, selectively inhibits type II fatty acid synthases . The mode of the thiolactomycin action on the fatty acid synthase system of Escherichia coli was investigated . Of the six individual enzymes of the fatty acid synthase system, {acyl-carrier-protein} (ACP) acetyltransferase and 3-oxoacyl-ACP synthase were inhibited by thiolactomycin . On the other hand, the other enzymes were not affected by this antibiotic . The thiolactomycin inhibition of the fatty acid synthase system was reversible . As to ACP acetyltransferase, the inhibition was competitive with respect to ACP and uncompetitive with respect to acetyl-CoA . As to 3-oxoacyl-ACP synthase, the inhibition was competitive with respect to malonyl-ACP and noncompetitive with respect to acetyl-ACP . The thiolactomycin action on the fatty acid synthase system was compared with that of cerulenin. Arch Surg, 1986 May, 121(5), 580 - 6 Diagnosis and treatment of splenic fungal abscesses in the immune-suppressed patient; Helton WS et al.; In an 18-month period candidal splenic abscesses were diagnosed and treated in eight patients . Predisposing factors consisted of recent exposure to cytotoxic chemotherapy, long-term use of prednisone, neutropenia, antibiotic therapy for greater than three weeks, and gastroint