Antibiotics

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 gastrointestinal tract colonization with Candida . The patients had a clinical profile of nontoxic appearance with a temperature of more than 38.5 degrees C that was unresponsive to antibiotics, pain and tenderness over the upper abdominal quadrants, focal defects visualized on ultrasound and/or computed tomographic scans, and an elevated alkaline phosphatase level . Candida infection was confirmed by histologic examination of the liver and/or spleen in all patients . Diagnosis was made by percutaneous biopsy in one patient and exploratory laparotomy in seven . Five patients had splenectomy and antifungal drugs . In three patients the fungal abscesses resolved with amphotericin B therapy alone . Seven of eight patients were cured of their splenic abscesses, and five of eight were long-term survivors.

Blood, 1986 May, 67(5), 1302 - 8
Depletion of donor lymphocytes by counterflow centrifugation successfully prevents acute graft-versus-host disease in matched allogeneic marrow transplantation; de Witte T et al.; Bone marrow from 22 histocompatible siblings was depleted of 98% of the lymphocytes using a combination of density flotation centrifugation followed by counterflow elutriation . Even with the marrow suppressive influence of methotrexate (MTX), the viability of the hematopoietic stem cells was not affected, as indicated by the normal repopulation after grafting in the evaluable patients . One patient (UPN 9) showed a primary graft failure, possibly resulting from persisting septicemia and long-term antibiotic therapy . Two patients have persistent host lymphocytes, one of whom was examined during relapse; the other remains in remission . Two patients did not receive immunosuppression after bone marrow transplantation (BMT), and acute graft-v-host disease (GVHD) developed in both . Nine patients received MTX as immunosuppression following BMT . GVHD did not develop in any of them, but fatal infections in the immediate posttransplant period developed in five patients . Eleven patients received cyclosporine (CsA) after transplantation . Beginning in week 5 after BMT, CsA was gradually replaced by MTX . Acute GVHD, substantial chronic GVHD, or fatal infections did not develop in any of these patients . Removal of 98% of the lymphocytes by counterflow centrifugation prevents development of acute GVHD, provided that immunosuppression is administered after BMT . Graft rejection was not observed, but the number of evaluable patients is limited at present.

J Immunol Methods, 1986 May 1, 89(1), 37 - 47
Generation of purified stromal cell cultures that support lymphoid and myeloid precursors; Dorshkind K et al.; Treatment of Dexter-type long-term bone marrow cultures with the antibiotic mycophenolic acid (MPA) eliminates all hemopoietic cells from the cultures, while a morphologically intact, adherent stromal cell layer is retained . The ability of these MPA treated stromal cell cultures to support long-term hemopoiesis was tested by seeding them with fresh bone marrow cells that had been passed through nylon wool . This procedure yields a relatively stromal cell depleted population of hemopoietic cells . An aliquot of 5 X 10(5) or 2.5 X 10(5) nylon wool passed bone marrow cells bearing the T6 chromosomal marker was seeded onto replicate MPA-treated stromal cell layers . The stromal cells stimulated the proliferation of the bone marrow cells, and nonadherent cells were present for up to 8 weeks of culture . Progenitors of granulocytes and macrophages (CFU-GM) were also present for this period of time despite weekly demi-depopulation, during culture feeding . Karyotypic analysis confirmed that the CFU-GM were derived from the reseeded population . Nylon wool-passed bone marrow cells seeded alone into empty flasks under identical conditions did not survive past 1 week . Cells from the reseeded cultures were also tested for early myeloid precursors (CFU-S) and injected into immunodeficient CBA/N mice to test for the presence of primitive B cell precursors . CFU-S were present in mice killed 11 days following injection of cells, and high levels of B cell colony-forming units (CFU-B) were present in mice 4 weeks post reconstitution . Further studies demonstrated that factors present in medium conditioned by the stromal cells could support the growth of CFU-GM . These data indicate that treatment of long-term bone marrow cultures with MPA results in a population of functional stromal cells.

Jpn J Antibiot, 1986 May, 39(5), 1427 - 31
{Imipenem/cilastatin sodium in the treatment of obstetric and gynecologic infections}; Doko F; Imipenem/cilastatin sodium (MK-0787/MK-0791), a carbapenem antibiotic and a dehydropeptidase-I inhibitor, was administered at a dose of 500 mg/500 mg twice a day for 5 days for the treatment of obstetric and gynecologic infections . A total of 10 patients was evaluated, and the clinical results were rated as excellent in 1, good in 7 and poor in 2 patients . As a side effect, rash was observed in 1 patient but it disappeared by the third day after the treatment was discontinued . No abnormal laboratory findings were observed in our study.

Jpn J Antibiot, 1986 May, 39(5), 1389 - 400
{A study on the penetration of imipenem/cilastatin sodium into the female genital tissues}; Hongo M et al.; A new carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), was administered by intravenous drip infusion at a dose level of 500 mg/500 mg to 30 patients who underwent total abdominal hysterectomy for uterine myomas with or without benign ovarian tumors . The uterine arteries were clamped bilaterally at 0.25, 0.5, 1, 2, 3, 4, 6 and 8 hours after administration, and plasma samples and uterine tissues were taken for measurements of MK-0787 by bioassay and MK-0791 by HPLC . The measured values were analyzed using a two-compartment open model . Maximum concentrations of MK-0787 at 0.5 hour after the start of intravenous drip infusion were 98.5 micrograms/ml in the antecubital vein, 100.1 micrograms/ml in the uterine artery, 26.5 micrograms/g in the oviduct, 21.2 micrograms/g in the ovary, 19.1 micrograms/g in the endometrium, 19.0 micrograms/g in the myometrium, 22.1 micrograms/g in the cervix uteri and 16.4 micrograms/g in the portio vaginalis . These results suggest that the penetration of MK-0787/MK-0791 into female genital tissues is good, and sufficient concentrations are obtained enough to inhibit organisms which are frequently isolated from patients with pelvic inflammatory disease.

Jpn J Antibiot, 1986 May, 39(5), 1372 - 82
{Experience with imipenem/cilastatin sodium in the field of obstetrics and gynecology}; Kohara T et al.; Fundamental and clinical studies on a new carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), were carried out in the field of obstetrics and gynecology . The following results were obtained . The concentration of MK-0787 in uterine tissue was 3.5 approximately 8.2 micrograms/g at about 30 minutes after an administration of 0.5 g/0.5 g of MK-0787/MK-0791 by a 30-minute intravenous drip infusion . The concentration decreased to less than 0.5 microgram/g by approximately 3 hours . The level of MK-0787 in the pelvic dead space exudate reached a peak of 24.0 +/- 4.4 micrograms/ml at 1 hour after an administration of MK-0787/MK-0791 0.5 g/0.5 g and was higher than the plasma level at 1 hour . The level in the pelvic dead space exudate was 2.0 +/- 0.8 microgram/ml at about 6 hours . The MK-0787/MK-0791 was administered to 4 patients with gynecologic infections (2 patients with pelvic peritonitis, 1 patient with salpingitis, 1 patient with a vulvar abscess) . The clinical efficacy was good in all 4 patients . Neither adverse effects nor abnormal laboratory findings were observed . It appears that MK-0787/MK-0791 is a safe and useful antibiotic for the treatment of obstetrical and gynecological infections.

J Am Dent Assoc, 1986 May, 112(5), 646 - 8
Extensive subcutaneous emphysema crossing the midline after a surgical extraction: report of case; Belfiglio EJ et al.; A case of extensive subcutaneous emphysema is reported . The patient had a mandibular third molar extracted but did not experience any cervical edema until the morning after surgery . The emphysema did not appear to be caused by the surgical procedure, as emphysema caused by use of instruments becomes immediately apparent and no patient-related causes could be documented . However, a dressing of a tetracycline-steroid ointment in a petrolatum base and a hemostatic agent was placed in the tooth socket during surgery and the dressing may have allowed air into the deeper tissues . The patient was managed by hospitalization, antibiotic therapy, and rest . The tissue emphysema resolved gradually during a 5-day period.

Gan To Kagaku Ryoho, 1986 May, 13(5), 1887 - 92
{Phase II study of epirubicin in inoperable or recurrent gastric cancer}; Sakata Y et al.; A phase II clinical trial of epirubicin, a new anthracycline anticancer antibiotic, was carried out in 41 patients with inoperable or recurrent gastric cancer . Epirubicin was administered by i.v . injection; the dosages were either 40-60 mg/m2 every three weeks (Regimen A) or 20-30 mg/m2/day for 3 days every three weeks (Regimen B) . Twenty-one patients were entered into Regimen A, and 20 into Regimen B . Of 31 evaluable patients, 16% (5/31) experienced objective response (PR); i.e., 20% (three of 15) treated with Regimen A and 13% (two of 16) with Regimen B, showing that there was no significant difference in the rate of response between the two regimens . Adverse effects observed were relatively mild in most cases and included anemia, leukopenia, thrombocytopenia, anorexia, nausea/vomiting, diarrhea, stomatitis and alopecia . Tachycardia and extrasystole were observed in 3 cases but disappeared upon discontinuation of the treatment . In conclusion, epirubicin seemed to have therapeutic activity comparable to that of doxorubicin in gastric cancer while being less toxic than doxorubicin, and is expected to become a better alternative to the latter drug.

Anticancer Res, 1986 May-Jun, 6(3 Pt B), 451 - 64
A novel approach for improving the efficacy of experimental cancer chemotherapy using combinations of anticancer drugs and L-histidinol; Warrington RC; One of the major limitations to the chemical management of human malignancies is the failure of most antineoplastic agents to act specifically against tumour cells . A novel approach for improving both the specificity and the efficacy of experimental cancer chemotherapy is described in this review . The approach is based upon the use of L-histidinol in combination with conventional anticancer drugs . L-Histidinol, a structural analogue of the essential amino acid L-histidine, is a reversible inhibitor of protein biosynthesis which evokes disparate responses from non-tumorigenic and tumorigenic cells in culture . Whereas L-histidinol protects a wide variety of phenotypically normal cells from anticancer drug toxicity, it enhances the vulnerability of tumorigenic cells to the same agents . More importantly, these remarkable properties of L-histidinol are retained in tumour-bearing animals . Thus, L-histidinol diminishes the myelocytoxicity otherwise associated with the in vivo use of agents such as cytosine arabinoside and 5-fluorouracil . Simultaneously, L-histidinol increases the inherent capacities of these two antimetabolites to eradicate in situ tumour cells . More recently, it has been found that L-histidinol can increase both the specificity and the efficacy of a number of other antineoplastic agents . For example, alkylating agents such as BCNU, cyclophosphamide and cis-platinum, as well as the antitumour antibiotic daunomycin, can be combined with L-histidinol to provide curative treatment for tumour-bearing animals under conditions where these drugs, on their own, have little or no impact on survival . These results demonstrate that the L-histidinol/anticancer drug combination approach to chemotherapy is effective with a variety of clinically-relevant antineoplastic agents . However, it remains to be demonstrated whether this approach will prove applicable in, or effective for, human cancer chemotherapy.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1986 May, 261(3), 330 - 7
Studies on the degradation of imipenem within serum and a renal kidney fraction; Koller M et al.; The degradation of imipenem in vitro was analyzed using reversed-phase HPLC . The incubation of imipenem with a microsomal kidney fraction revealed the generation of two metabolites (UV-maxima at 275 or 308 nm, respectively) . The metabolism of imipenem by the renal enzyme was completely inhibited by cilastatin (2 micrograms/ml) . The lowest detectable inhibitory concentration of cilastatin was at 6.5 X 10(-10) M . The recovery of imipenem from serum was 52.6% after incubation for 2 h at 37 degrees C . The stability of the antibiotic within serum was improved by 13.9% in the presence of EDTA (10 mM) indicating a possible involvement of serum dipeptidases in the systemic breakdown of the imipenem molecule.

Am J Hosp Pharm, 1986 May, 43(5), 1222 - 5
Personnel costs and preparation time in a centralized intravenous admixture program; Ryan DM et al.; The amount of time and the cost of personnel time associated with the preparation of injectable products were determined . A time study consisting of 9041 observations during a seven-day period was conducted to determine the amount of time required of pharmacists and technicians for the preparation of total parenteral nutrient (TPN) solutions, large-volume injectables, antibiotic admixtures, antineoplastic admixtures, and investigational drugs . The established times were used to calculate relative value units for each product line and to determine the cost of pharmacist and technician time associated with the preparation of each product line . Preparation times ranged from 3.7 minutes for an antibiotic admixture to 49 minutes for a pediatric TPN solution . Total personnel costs ranged from $0.71 for an antibiotic admixture to $10.70 for a pediatric TPN solution . The calculated relative value units indicated that existing departmental time standards did not allow sufficient time for the preparation of some products . Establishing relative value units and calculating the cost of personnel time associated with the preparation of injectable products can be helpful for comparing the cost of purchasing ready-to-use products with the cost of preparing the same products.

Pharmacol Res Commun, 1986 May, 18(5), 451 - 7
The neuromuscular blocking activity of spectinomycin on the rat sciatic nerve-gastrocnemius muscle preparation; Renna G et al.; Spectinomycin displays a dose-dependent neuromuscular blocking activity in vivo . The neuromuscular blockade elicited by spectinomycin is potentiated by d-tubocurarine . Neostigmine methylsulfate is unable to reverse the neuromuscular blocking activity of spectinomycin, whereas calcium chloride counteracts the neuromuscular blockade induced by this antibiotic.

Plasmid, 1986 May, 15(3), 210 - 6
Plasmids related to RSF1010 from Bordetella bronchiseptica; Lax AJ et al.; Six out of 14 Bordetella bronchiseptica isolates from U.K . pigs each contained one plasmid, of 8.7-44 kb . All plasmid-containing isolates were sulfonamide resistant, and this property was shown to be plasmid-encoded . Five of the plasmids were related; two were indistinguishable from the broad-host-range plasmid, RSF1010 . The other three, two of which appeared to be identical, were shown to have regions of homology with RSF1010 . One of these regions encompassed the sulfonamide resistance determinant while the other contained oriV, which also determines plasmid incompatibility . None of the plasmids could be associated with virulence or phase variation, and it appears likely that they have been acquired in response to antibiotic pressure.

J Clin Oncol, 1986 May, 4(5), 767 - 74
Phase I study of intravenous menogaril administered intermittently; Dodion P et al.; Thirty-three adult patients with solid tumors were treated with menogaril, a new anthracycline antibiotic . The drug was given as a two-hour infusion every 4 to 5 weeks at doses ranging from 17 to 250 mg/m2 . The maximum tolerated dose was 250 mg/m2 . Reversible and dose-related leukopenia was the dose-limiting toxicity . Thrombocytopenia was less frequent . Hematologic toxicity was maximal 2 weeks after treatment, and recovery usually occurred within 4 weeks . There was no dissociation between WBC and neutrophil counts, and myelosuppression did not appear to be cumulative up to 200 mg/m2 . Myelosuppression was more severe for patients with heavy pretreatment and/or bone marrow involvement . Local toxicity consisting of phlebitis and/or erythema was the most common nonhematologic toxicity, especially at 250 mg/m2 (eight out of nine patients) . Usually, erythema appeared within 24 hours after treatment at or near the infusion site and resolved within a few days . Occasionally, a more persistent (several weeks) orange discoloration suggesting cutaneous deposits of menogaril was observed . Nausea and vomiting were uncommon and never severe . Alopecia and mucositis were rare . Minor arrhythmias were seen in several patients during treatment, but their relationship with menogaril therapy was unclear, and in no patient did heart failure develop . Plasma concentrations were best described by a tricompartmental model with a mean terminal half-life of 29.5 hours and a mean total-body clearance of 20.2 L/h/m2 . Doses of 160 and 200 mg/m2 are recommended for phase II trials in poor- and good-risk patients, respectively.

Minerva Med, 1986 Apr 21, 77(17), 663 - 9
{Bacampicillin vs amoxicillin in respiratory pathology}; Di Nola F et al.; Clinical research was conducted to evaluate the comparative therapeutic efficacy in respiratory pathology of 800 mg X 2 per diem bacampicillin v . 1000 mg X 2 per diem amoxicillin, both orally administered . The results were more or less identical and are interpreted as indicating the better constant absorption of the precursor, hence its higher concentration gradient that produces a higher antibiotic concentration in the lungs.

Biochem Biophys Res Commun, 1986 Apr 14, 136(1), 322 - 8
Inhibition of SV40 DNA replication in vitro by 1-N-acyl-3"-N-(trifluoroacetyl) kanamycin; Yamaki H et al.; A new antiviral aminoglycoside antibiotic, 1-N-eicosanoyl-3''-N-(trifluoroacetyl) kanamycin, was found to inhibit SV40 DNA replication in vitro . Several other aminoglycoside antibiotics examined did not exhibit a significant inhibition of SV40 DNA replication . The elongation of the SV40 DNA strand was profoundly affected by this agent . The degree of inhibition was decreased by increasing the amount of DNA template, but not by increasing the amount of enzyme . The inhibition of SV40 DNA replication is attributed to the interaction between the agent and the DNA template.

Chest, 1986 Apr, 89(4), 613 - 5
Aortic root abscess . Initial experience using magnetic resonance imaging; Jeang MK et al.; The detection of aortic root abscess by magnetic resonance imaging has not been described previously . We report a patient with an aortic root abscess that was successfully diagnosed by magnetic resonance imaging and echocardiography . Computed tomography failed to detect the abscess . The patient recovered with antibiotic therapy . Based on this case and other reports in the literature, we advocate treating similar patients without surgery . We recommend magnetic resonance imaging as an investigational method where the diagnosis of aortic root abscess is ambiguous.

Int Surg, 1986 Apr-Jun, 71(2), 91 - 4
Management of 240 cases of liver abscess; Mehta RB et al.; The clinical features and surgical management of 240 cases of liver abscess admitted during a period of five years are presented . Incidence of liver abscess was 0.20 per cent of hospital admissions . A peak age incidence in the 4th decade, male preponderance, pain and fever were the striking features . The majority of the abscesses were localised to a single lobe (90.0%) . The abscess was sited in the right lobe in 75.1 per cent, in the left lobe in 18.3 per cent and in both lobes in 6.7 per cent . Elevation and limitation of movement of the right dome of the diaphragm was present in 89.5 per cent of cases . Depending upon therapeutic response, aspiration or/and surgical drainage was undertaken . Aspiration was done in 169 patients and surgical drainage in 63 patients . Management of pyogenic liver abscess included early operative intervention preceded by appropriate antibiotic therapy . Surgical intervention is required less often in amoebic abscess and is recommended only after amoebicidal therapy . Open drainage is recommended for the cases associated with complications, left lobe abscess and big abscess.

Br J Dis Chest, 1986 Apr, 80(2), 131 - 7
Mycobacterium kansasii: colonization and disease; Schraufnagel DE et al.; Mycobacterium kansasii has a wide range of virulence from fatal disease to infection and colonization . The laboratory report of growth of M . kansasii is often a problem for the clinician and an encumberance for the patient . To determine the difference between patients who had disease from M . kansasii and those from whom it was isolated without causing disease, we compared the records of 70 patients from whom this mycobacterium was isolated . The group with disease was defined as those patients with more than one culture with luxuriant growth and new, compatible symptoms, signs or radiographic changes . Age, sex, occupation, place of birth and residence, past medical history, skin testing, radiographic changes, in vitro antibiotic sensitivities, and the time and source of the isolation were tabulated . The group without compatible disease had only a single isolate and almost never had any new symptom or sign . Patients with disease from M . kansasii were more often male (P less than 0.02) and had more chronic obstructive lung disease (P less than 0.001) . Patients without disease more frequently had isolations from laryngeal swabs (P less than 0.001) . The cultures of these swabs had less stringent laboratory decontamination . M . kansasii may be a more frequent colonizer of the upper airway than previously thought . Clinicians should use the same rigorous definition of disease caused by M . kansasii as clinical investigators, namely repeated isolations with luxuriant growth in an appropriate host . The laboratory, instead of the clinician, should investigate positive cultures in patients without disease.

Avian Dis, 1986 Apr-Jun, 30(2), 421 - 5
Fatal cryptosporidiosis in quail; Hoerr FJ et al.; Young quails kept in wire-floored cages experienced high mortality, beginning at age 5 days, from diarrhea that was unresponsive to antibiotic therapy . At necropsy, the small intestine had clear fluid content and the cecum was distended by brown foamy fluid . Histopathologic findings in the small intestine were shortened villi with detached enterocytes at the tip . Cryptosporidium sp . (confirmed by electron microscopy) were numerous in the microvillous border . Neither bacterial nor viral pathogens were detected . No infection was established in day-old chickens gavaged with feces and intestinal contents from infected quails . Thorough cleansing of the cages followed by application of commercial bleach prevented recurrence.

Antibiot Med Biotekhnol, 1986 Apr, 31(4), 280 - 3
{Pharmacokinetics of amphoglucamine in an experiment}; Fateeva LI; The pharmacokinetics of amphoglucamine administered in a single dose or used for a treatment course orally or in the form of aerosols was studied on experimental animals . It was shown that amphoglucamine was absorbed after either its oral administration or its administration in the form of aerosols . The use of the drug during the treatment course resulted in an increase in the antibiotic levels and the period of its renal excretion in the animals.

Antibiot Med Biotekhnol, 1986 Apr, 31(4), 277 - 80
{Effect of cefuroxime on embryonic and fetal development in an experiment}; Skosyreva AM et al.; The direct and indirect effects of cefuroxime on the embryo and fetus were studied in vitro and in vivo at different gestation times . The placenta, liver and kidneys of the mother and fetus were investigated morphologically . It was shown that in a dose of 250 mg/kg the antibiotic did not induce disorders in the fetus development . The histological examination of the fetus placenta and liver revealed no changes as compared to the controls . However, in the renal tubules of the mother and fetus, pathological lesions in the form of the cytoplasm granular degeneration and nucleus swelling, lysis and necrosis were observed . These lesions were of a dose-dependent character . The possible nephrotoxic effect of cefuroxime prevents its use as a drug of choice in treatment of gestation pyelonephritis.

Unfallchirurgie, 1986 Apr, 12(2), 81 - 92
{Treatment of bone infection in the area of the skull}; Knoringer P; Osteomyelitis in the skull region is encountered preferably as a postoperative, but also as a posttraumatic lesion, furthermore it occurs in case of infection of the paranasal sinuses or, rarely, as hematogenic metastasis . The routine treatment comprises a careful wound cleaning with excision of fistula, resection of the osteomyelitic bone and ablation of all purulent and devital tissues, eventually sanitation of an infected paranasal sinus . Between six and twelve months after the healing of the infection, the bone defect is closed by plastic surgery . In 1976, we have introduced Refobacin-Palacos R for the local treatment of the infection with simultaneous definitive closing of the bone defect in case of osteomyelitis of the skull . 44 patients have been treated since with this method . The rate of reinfection was 3% in osteomyelitis of the calotte without involvement of the sinuses and 25% in case of involvement of the frontal sinuses . A twofold method has been developed in order to reduce the relatively high frequency of reinfection in case of involvement of the frontal sinuses . The wound cleaning with revision of the frontal sinuses and parenteral administration of antibiotic drugs was performed as usual . An additional local treatment of the infected frontal sinuses was performed by implantation of Septopal chains which were removed ten to fourteen days later . During the same session the nasal excretory ducts were closed and the frontal sinuses largely filled up with muscle pieces together with a compound of spongiosa, fibrin, and antibiotic . The remaining bone gap was closed with Refobacin-Palacos R . A significantly decreased reinfection rate is anticipated with this twofold procedure, however, a clear statement is not yet possible due to the small number of cases and the relatively short follow-up period.

Sex Transm Dis, 1986 Apr-Jun, 13(2), 67 - 70
Vaginal colonization with mycoplasma hominis and ureaplasma urealyticum; McCormack WM et al.; Vaginal cultures obtained from unselected young women who consulted the gynecologist in a student health service were examined for Ureaplasma urealyticum and Mycoplasma hominis . Each participant completed a confidential questionnaire . Multiple logistic regression analysis was used to determine which variables, of a large number ascertained, were associated with mycoplasmal colonization . U . urealyticum was isolated from 273 (56.8%) of 481 participants . The following variables were significantly predictive of colonization with U . urealyticum: black race, absence of antibiotic use, cigarette smoking, and number of sexual partners during the last year . Lifetime number of sexual partners was significantly predictive only in women who used nonbarrier methods of contraception . M . hominis was isolated from 85 (17.7%) of the 481 participants . Independent variables that were significantly predictive of colonization with M . hominis included black race, young age, and, for users of nonbarrier methods of contraception, lifetime number of sexual partners.

J Otolaryngol, 1986 Apr, 15(2), 108 - 11
Malignant external otitis; McShane D et al.; Malignant external otitis was first identified by Chandler in 1968 as a significant otologic entity . Since then its mortality rate has steadily declined . This is due to increased awareness, earlier diagnosis and appropriate antibiotic therapy . A review of five years' experience with this condition at Mount Sinai Hospital, Toronto, is presented . The use of radionuclide scanning in diagnosis and determining duration of therapy is stressed.

Int J Clin Pharmacol Ther Toxicol, 1986 Apr, 24(4), 180 - 7
Biliary elimination of apalcillin: an experimental and clinical study; Brogard JM et al.; After adding 10 mg of apalcillin to the circulating blood of five isolated rabbit liver perfusion preparations, total apalcillin biliary recovery over a 3 h-period accounted for 30.7% of the administered dose; the biliary peak level averaged 686.0 +/- 135.9 micrograms/ml . In five healthy subjects, a maximum level of 1088 +/- 582 micrograms/ml was measured in the duodenal fluid collected during 4 h following intravenous injection of 1 g of apalcillin . In 10 cholecystectomized patients provided with T-tube drainage, after the same dosage, a biliary peak of 2093 +/- 859 micrograms/ml was attained in the 3rd hour and cumulative biliary recovery over a 12 h-period amounted to 12.1% of the injected dose . In 20 patients undergoing biliary surgery, intra-operative simultaneous sampling performed 1 h after intravenous injection of 1 g of apalcillin showed antibiotic levels of 65.5 +/- 5.0 micrograms/ml in serum, 3860 +/- 551 micrograms/ml in common bile duct bile and 2552 +/- 627 micrograms/ml in gallbladder bile . The results of these investigations were compared with data previously obtained with 13 other beta-lactam derivatives.

Antimicrob Agents Chemother, 1986 Apr, 29(4), 570 - 5
Trichodermin esterase activity and trichodermin resistance in Mucor racemosus; Fonzi WA et al.; Mucor racemosus exhibited inducible phenotypic resistance toward the protein synthesis inhibitor trichodermin . Induction of resistance was elicited by exposure to trichodermin or to cycloheximide . Both adapted and nonadapted cells took up {14C}trichodermin from the medium . Trichodermin was found to be rapidly deacetylated to trichodermol upon entering the cell . Adapted cells deacetylated the drug more rapidly than nonadapted cells both in vivo and in vitro . The trichodermol resulting from deacetylation appeared in the medium, but the growth of adapting cells began well before the total conversion of trichodermin to trichodermol . Based on these data and the observation that trichodermol was a poor inhibitor of Mucor, adaptation appears to result from deacylation of the active antibiotic.

Drug Intell Clin Pharm, 1986 Apr, 20(4), 281 - 3
Cefoperazone-induced coagulopathy; Freedy HR Jr et al.; A number of recent articles have reviewed the problem of hypoprothrombinemia and bleeding associated with antibiotic therapy . We report three cases in which bleeding is believed to be related to a prolonged prothrombin time secondary to cefoperazone therapy . Reports of coagulopathies such as these are increasing in number and call attention to the need to monitor the prothrombin time during cefoperazone therapy.

Compr Ther, 1986 Apr, 12(4), 56 - 61
Diagnosis and treatment of cryptosporidiosis in children; Kocoshis SA; Clinicians have only recently become aware that Cryptosporidium is a major human pathogen, causing a self-limited gastroenteritis in immunocompetent individuals and profound enteropathy in the immunocompromised . Among the immunologically intact, children appear more prone to clinically significant cryptosporidiosis than do adults . Diagnosis is most easily made by a specialized three-step stool examination, but mucosal biopsy may also be necessary to establish the diagnosis . Although no satisfactory antibiotic therapy exists today, cases of cryptosporidiosis in the community and hospital should be identified in order to contain human transmission . Only then can spread from immunocompetent individuals to immunodeficient individuals be avoided.

Genetika, 1986 Apr, 22(4), 593 - 8
{The need for protein synthesis in UV-irradiated Escherichia coli cells for fixation of induced Str mutations}; Filippov VD et al.; The kinetics of accumulation of fixed Str mutations was determined during incubation in nutritional medium of Escherichia coli WP2 irradiated with 6.8 J/m2 either at log growth phase or after completion of DNA replication . Those Str mutations which lost ability for photoreactivation (fixation I) or susceptibility to antimutagenic activity of mfd-type (fixation II) were considered as fixed mutations . It was shown that both fixations occurred synchronously, starting in about 10 min after irradiation and being over in 40-50 min . In cells irradiated after completion of replication, fixation depended on protein synthesis de novo: chloramphenicol added to irradiated culture blocked fixation . An attempt to study the effect of chloramphenicol on fixation in a culture irradiated at the log phase failed, because of high lethal action of the antibiotic on such cells . Fixation could proceed in the presence of acriflavine . Possible mechanisms for fixation of Str mutations are discussed in connection with the fact of its dependence on protein synthesis.

Aust N Z J Surg, 1986 Apr, 56(4), 341 - 6
Liver abscess in Western Australia (1974-1983); Levitt MD et al.; Over the 10 year period 1974-1983, 91 cases of liver abscess presented to the major teaching hospitals in Perth, Western Australia . Amoebic liver abscess (ALA) accounted for 37 (or 41%) of these cases, an incidence inflated by Perth's proximity to south-east Asia where amoebiasis is endemic . This frequent recent history of contact, the availability of sensitive and specific diagnostic serology and a clinical presentation usually suggesting pathology in the right upper quadrant, accounted for the consistently short delay in diagnosis of ALA . There were no deaths from ALA and a low incidence of complications such as secondary infection or rupture into the thorax . On the other hand, pyogenic liver abscess (PLA) commonly presented in a more non-specific manner and in an older age group, contributing to a long delay in diagnosis . Despite improvements in liver imaging techniques and advances in antibiotic and general supportive therapy, mortality for PLA remains high, 20% in this series . Fatal PLA was associated with multiple abscesses not amenable to drainage, increasing age, delay in diagnosis and the presence of septicaemia.

J Gen Virol, 1986 Apr, 67 ( Pt 4), 707 - 17
Hantaan virus replication: effects of monensin, tunicamycin and endoglycosidases on the structural glycoproteins; Schmaljohn CS et al.; The monovalent ionophore monensin, which interferes with cellular transport pathways, and the antibiotic tunicamycin, which prevents glycosylation of newly synthesized proteins, were used to examine Hantaan virus particle formation and polypeptide synthesis . Viral replication in the presence of either drug resulted in reduced antigen production as well as reduced yields of both intracellular and extracellular infectious virus . Analysis of viral polypeptides synthesized in the presence of the drugs suggested differential effects of monensin and tunicamycin on Hantaan virus . Although reduced levels of the three major structural proteins were detected with increasing concentrations of monensin, the electrophoretic migrations of the polypeptides synthesized were unaltered . In contrast, after tunicamycin treatment, G1 was no longer detectable and G2 displayed both a quantitative reduction and an apparent molecular weight reduction of approximately 3000 . Both G1 and G2 were sensitive to endoglycosidases H and F with resultant electrophoretic mobility shifts corresponding to molecular weights of approximately 7000 for G1 and 3000 for G2 . Oligosaccharides appeared to be mostly, but not entirely, of the high-mannose type.

J Gen Virol, 1986 Apr, 67 ( Pt 4), 793 - 9
Polyoma virus middle T gene can trigger malignant transformation of early passage rodent cells; Spandidos DA et al.; Previous studies on the tumourigenic conversion of early passage rat embryo cells by the polyoma virus early genes have suggested a multigenic control of tumourigenesis . Thus, the large T gene can immortalize early passage rat cells and can relieve the serum dependence of normal and transformed cells . The middle T gene alone cannot immortalize early passage cells; however, it can induce cells of established cell lines to become anchorage-independent and tumourigenic . Here we show that when linked to transcriptional enhancers, the polyoma virus middle T gene can trigger the complete malignant transformation of early passage rodent cells . Therefore, the polyoma virus middle T gene does not require a cooperating oncogene to induce malignant conversion of these cells.

EMBO J, 1986 Apr, 5(4), 773 - 8
The selectivity filter of voltage-dependent channels formed by phosphoporin (PhoE protein) from E . coli; Dargent B et al.; Phosphoporin, an Escherichia coli outer membrane-spanning protein re-incorporated in phospholipid planar bilayers generates aqueous channels similar to those of matrix porin . One phosphoporin trimer contains three pores which are induced simultaneously but fluctuate separately between open and closed states . Membrane potential shifts this two-state equilibrium in favour of closed channels . This negative resistance occurs at lower potentials than with matrix porin channels . The phosphoporin channel is poorly anion selective for small solutes . Polyphosphates and other phosphorylated molecules specifically inhibit phosphoporin pore conductance to small ions, a property which is specific to phosphoporin . There is an excellent correlation between the effect of such solutes measured in planar bilayers and their inhibitory effect on beta-lactam antibiotic uptake in vivo by phosphoporin . It is concluded that the phosphoporin channel contains a selectivity filter which is only efficient for larger molecules, most probably through basic residues.

Jpn J Cancer Res, 1986 Apr, 77(4), 324 - 6
Inhibition by sakyomicin A of avian myeloblastosis virus reverse transcriptase and proliferation of AIDS-associated virus (HTLV-III/LAV); Tanaka N et al.; In the course of screening for inhibitors of reverse transcriptase, we have isolated an inhibitor from a strain of Nocardia and identified it as sakyomicin A . The antibiotic blocks avian myeloblastosis virus reverse transcriptase reaction: IC50 was ca . 30 micrograms/ml by the method employed . The drug affects proliferation of HTLV-III/LAV in HTLV-I-carrying MT-4 cells: ca . 60% inhibition was observed at an antibiotic concentration of 1.0 microgram/ml and ca . 20% inhibition at 0.1 microgram/ml, and there was no significant cytotoxicity.

Biochim Biophys Acta, 1986 Mar 27, 856(1), 68 - 75
Orientation of gramicidin D incorporated into phospholipid multibilayers: a Fourier transform infrared-attenuated total reflection spectroscopic study; Okamura E et al.; Polarized Fourier transform infrared (FTIR)-attenuated total reflection (ATR) spectroscopy was applied to study the orientation of the linear pentadecapeptide antibiotic gramicidin D incorporated into phospholipid multibilayers, which were cast on a germanium ATR plate from chloroform solution . In DMPC and DPPC multibilayers, the CH2 stretching bands of lipid hydrocarbon chains were slightly shifted to the higher frequency side and bandwidth was increased in the presence of gramicidin . However, in DPPE multibilayers, frequencies and bandwidths of these bands were unaltered . In each case, gramicidin produced little effect on the orientation of lipid hydrocarbon chains, suggesting that gramicidin penetrates into lipid layers without noticeable perturbations . Upon incubation of cast films in contact with water above the gel-liquid-crystalline transition temperature (Tc) of lipids, the reorientation of gramicidin in lipid multibilayers occurred, the degree thereof depending upon the fluidity of the lipid hydrocarbon chains and the amount of surrounding water . In DMPC multibilayers, the helix axis of gramicidin was oriented almost parallel to the lipid hydrocarbon chains after incubation . In DPPC multibilayers, on the other hand, the helix axis of gramicidin was tilted on average about 15 degrees from the lipid hydrocarbon chains after incubation . However, in DPPE multibilayers, which are known to have the most rigid bilayer structures, the reorientation of gramicidin could not be seen.

J Mol Biol, 1986 Mar 20, 188(2), 207 - 14
Altered 40 S ribosomal subunits in omnipotent suppressors of yeast; Eustice DC et al.; The five suppressors SUP35, SUP43, SUP44, SUP45 and SUP46, each mapping at a different chromosomal locus in the yeast Saccharomyces cerevisiae, suppress a wide range of mutations, including representatives of all three types of nonsense mutations, UAA, UAG and UGA . We have demonstrated that ribosomes from the four suppressors SUP35, SUP44, SUP45 and SUP46 translate polyuridylate templates in vitro with higher errors than ribosomes from the normal stain, and that this misreading is substantially enhanced by the antibiotic paromomycin . Furthermore, ribosomal subunit mixing experiments established that the 40 S ribosomal subunit, and this subunit only, is responsible for the higher levels of misreading . Thus, the gene products of SUP35, SUP44, SUP45 and SUP46 are components of the 40 S subunit or are enzymes that modify the subunit . In addition, a protein from the 40 S subunit of the SUP35 suppressor has an altered electrophoretic mobility; this protein is distinct from the altered protein previously uncovered in the 40 S subunit of the SUP46 suppressor . In contrast to the ribosomes from the four suppressors SUP35, SUP44, SUP45 and SUP46, the ribosomes from the SUP43 suppressor do not significantly misread polyuridylate templates in vitro, suggesting that this locus may not encode a ribosomal component or that the misreading is highly specific.

J UOEH, 1986 Mar 20, 8 Suppl, 355 - 61
{Serum type III procollagen peptide in diagnosis of lung fibrosis due to silicosis and bleomycin toxicity}; Okuno F et al.; Early diagnosis of lung fibrosis has been hampered by the lack of a simple, convenient and specific test . Measurement of serum type III procollagen peptide (Pro (III)-N-P) by the method originally developed by Rohde et al . has been shown to be useful for the evaluation of hepatic fibrosis . The present study, therefore, was carried out to investigate the usefulness of the measurement of Pro (III)-N-P in 24 patients with lung fibrosis due to silicosis, and in 7 patients with malignant lymphoma treated with bleomycin, antitumor antibiotic which has the adverse effect of producing fibrosis in the lung . The normal value of the peptide in adults was 8.60 +/- 2.35 ng/ml (mean +/- SD; n = 68) and the normal upper level was set at 13.4 ng/ml (mean +/- 2SD) . Patients with silicosis had significantly but not extremely high levels of the peptide and 25% of the patients showed abnormally high values . The level of Pro (III)-N-P was associated with neither physical findings, chest X-p findings nor pulmonary function test results . Three of 7 patients showed increased levels during treatment with bleomycin . In one case, a total dose of 120 mg of bleomycin for over a period of 14 months markedly increased the level of the peptide . These observations suggest that the determination of Pro (III)-N-P may be useful for the detection of lung fibrosis.

Cancer, 1986 Mar 15, 57(6), 1092 - 6
Head and neck aspergillosis in patients undergoing bone marrow transplantation . Report of four cases and review of the literature; Schubert MM et al.; Aspergillus infection can be a major cause of morbidity in immunocompromised patients, especially when there is pulmonary involvement . Diagnosis of aspergillosis is often complicated by the varied clinical presentation and compromised medical status of such patients . Four cases of head and neck Aspergillus infections in bone marrow transplant patients are presented . Involvement predominantly was limited to the oral cavity and/or sinuses, and in one case, the ear . Two cases were successfully managed with a combined antibiotic and surgical approach, and one case with antibiotics only . The fourth case was managed with antibiotics and surgery, but fatal hemorrhage secondary to sinus involvement developed.

Biochemistry, 1986 Mar 11, 25(5), 1009 - 15
Generation of superoxide free radical by neocarzinostatin and its possible role in DNA damage; Chin DH et al.; Spectroscopic analysis of the reduction of both nitro blue tetrazolium and ferricytochrome c induced by neocarzinostatin shows that superoxide free radical is produced during the spontaneous degradation of the antibiotic . The amount of superoxide free radical produced from neocarzinostatin is not affected by the presence of thiol, although earlier work has shown that DNA damage is stimulated at least 1000-fold by thiol . Transition metals are not involved in this reaction . Although superoxide dismutase inhibits the reduction of nitro blue tetrazolium and cytochrome c induced by neocarzinostatin, neither it nor catalase interferes with the action of neocarzinostatin on DNA, whether or not drug has been activated by thiol . The pH profiles for spontaneous base release and alkali-labile base release (a measure of nucleoside 5'-aldehyde formation at a strand break) do not correspond with that for the generation of superoxide free radical from neocarzinostatin . The same holds for supercoiled DNA cutting by neocarzinostatin chromophore in the absence of a thiol, which is an acid-favored reaction . These results indicate that the generation of superoxide free radical by the drug does not correlate with DNA damage activity, whether or not thiol is present . Furthermore, the failure of hydroxyl free-radical scavengers to inhibit drug-induced single-strand breaks in supercoiled DNA in the absence of thiol also indicates that a diffusible hydroxyl free radical is most probably not involved in this reaction.

Nucleic Acids Res, 1986 Mar 11, 14(5), 2015 - 33
DNA sequence recognition by under-methylated analogues of triostin A; Low CM et al.; Two new analogues of TANDEM (des-N-tetramethyl triostin A) have been synthesised in an effort to elucidate the molecular basis of DNA nucleotide sequence recognition in this series of compounds . Their binding preferences have been investigated by DNAase I footprinting and differential inhibition of restriction nuclease attack . The presence of a single N-methyl group on only one valine residue (in {N-MeVal4} TANDEM) abolishes the ability to recognise DNA, presumably because this antibiotic analogue has suffered an unfavourable conformational change in the depsipeptide ring . A bis-methylated analogue, {N-MeCys3, N-MeCys7}TANDEM, was found to interact quite strongly with DNA and afforded binding sites, rich in AT residues, identical to those of TANDEM . Footprinting with various DNA fragments of known sequence showed that this analogue recognises sequences containing the dinucleotide TpA, although we cannot exclude the possibility that it binds to ApT as well . {N-MeCys3, N-MeCys7}TANDEM inhibits cutting by RsaI, a restriction enzyme that recognises GTAC but not by Sau3AI which recognises GATC . This provides further supportive evidence that the ligand (and, by extension, TANDEM itself) prefers binding to sequences containing the dinucleotide step TpA.

Nucleic Acids Res, 1986 Mar 11, 14(5), 2001 - 14
Footprinting reveals that nogalamycin and actinomycin shuffle between DNA binding sites; Fox KR et al.; The hypothesis that sequence-selective DNA-binding antibiotics locate their preferred binding sites by a process involving migration from nonspecific sites has been tested by footprinting with DNAase I . Footprinting patterns on the tyrT DNA fragment produced by nogalamycin and actinomycin change with time after mixing the antibiotic with the DNA . Sites of protection as well as enhanced cleavage are seen to develop in a fashion which is both temperature and concentration-dependent . At certain sites cutting is transiently enhanced, then blocked . Limited evidence for slow reaction with echinomycin and mithramycin is presented, but the kinetics of footprinting with daunomycin and distamycin appear instantaneous . The feasibility of adducing direct evidence for shuffling by footprinting seems to be governed by slow dissociation of the antibiotic-DNA complex . It may also be dependent upon the mode of binding, be it intercalative or non-intercalative in character.

FEBS Lett, 1986 Mar 3, 197(1-2), 285 - 8
Neomycin: a specific drug to study the inositol-phospholipid signalling system?
Prentki M, Deeney JT, Matschinsky FM, Joseph SK.
Neomycin, an antibiotic previously thought to interact specifically with inositol-containing phospholipids, was found to inhibit IP3-mediated Ca2+ release from the intracellular stores of permeabilized insulinoma and liver cells . This inhibition could be relieved by increasing the IP3 concentration . Radiolabelled IP3 was found to bind tightly to columns prepared from neomycin covalently attached to glass beads . ATP was also bound by these columns . It is concluded that neomycin acts in biological systems as a weak anion exchanger and is therefore unsuitable for use as a specific tool to study the role of inositol phospholipids in intracellular signalling.

Br J Ophthalmol, 1986 Mar, 70(3), 174 - 8
Orbital cellulitis; Bergin DJ et al.; Forty-nine cases of orbital cellulitis were reviewed . The average age of patients at presentation was 31 years . The onset of symptoms varied from seven days or less in 28 patients, one to four weeks in 17 patients, and more than four weeks in four patients . The leucocyte count, available in 33 patients, was greater than 10 X 10(9)/l in only nine . Abnormal sinuses were noted radiographically in 61% . Computed tomography scans, performed on nine patients, revealed non-localised inflammation in three and an orbital mass in six . Cultures, in general, were disappointing . Seventeen surgical procedures were performed on 14 patients . The complications of orbital cellulitis, occurring in five patients, included osteomyelitis of the maxillary bone, strabismus, afferent pupillary defect, chronic draining sinus, and scarred upper eyelid . Usually the treatment of orbital cellulitis requires aggressive parenteral antibiotic therapy and judicious surgical intervention.

Am J Surg, 1986 Mar, 151(3), 409 - 11
Low pelvic abscesses . A technique of drainage using a small trocar catheter; Nivatvongs S; A low anterior pelvic abscess can be drained transrectally using a 16 F . trocar catheter or chest tube . The tube is anchored intrarectally for dependent drainage or for irrigation with a normal saline solution or an antibiotic solution . A low posterior pelvic abscess secondary to a low anterior resection can be drained transperineally in the same manner.

Am J Med, 1986 Mar, 80(3), 521 - 2
Bacteremic pneumococcal pneumonia and myoglobinuric renal failure; Marino PL et al.; A case of bacteremic pneumococcal pneumonia associated with rhabdomyolysis and myoglobinuric renal failure is presented . This may be the first report of the association of these two disorders, and may influence the choice of antibiotic selection in patients with rhabdomyolysis and a pulmonary infiltrate.

Arch Surg, 1986 Mar, 121(3), 282 - 4
Serum kinetics of intraperitoneal moxalactam; Fry DE et al.; Continuous intraperitoneal administration of antibiotics has been recommended as treatment for peritonitis . The necessity of simultaneous systemic administration of antibiotics remains undefined but usually is performed . Moxalactam kinetics in serum were studied in dogs receiving 15 mg/kg intravenously; 15 mg/kg intraperitoneally; 5 mg/kg hourly with peritoneal lavage; 15 mg/kg intravenously followed by 5 mg/kg hourly intraperitoneally; 15 mg/kg intraperitoneally after 24 hours of peritonitis; and 5 mg/kg hourly by peritoneal lavage after 24 hours of peritonitis . Intraperitoneally administered moxalactam resulted in sustained serum levels compared with intravenously administered drugs . Repeated exchanges in lavage fluid resulted in progressively higher serum levels with each exchange . Peritonitis results in statistically higher levels of serum antibiotic concentration when compared with controls . Continuous intraperitoneal lavage with antibiotics would not appear to require concomitant systemic drug therapy.

Cancer Res, 1986 Mar, 46(3), 1063 - 7
Biochemical mode of cytotoxic action of neplanocin A in L1210 leukemic cells; Inaba M et al.; Neplanocin A, a novel antitumor antibiotic, was investigated to determine the biochemical mode(s) of its cytotoxic action . The molecule is an adenosine analogue with a unique cyclopentane structure in its ribose moiety . Both sublines of L1210 and P388 leukemia resistant to neplanocin A were cross-resistant in vitro to bredinin and 9-beta-D-arabinofuranosyladenine, which have been reported to be activated by adenosine kinase . The adenosine kinase activity was markedly reduced in the resistant sublines as compared with that of the respective sensitive lines . Furthermore, neplanocin A competitively inhibited the phosphorylation reaction of adenosine in a cell-free system . The results indicate that neplanocin A is activated by adenosine kinase . Regarding the target site for neplanocin A, the antibiotic suppressed RNA synthesis to a significantly greater extent than DNA synthesis . This RNA-preferential effect is unique among common antimetabolic antitumor agents.

Arch Fr Pediatr, 1986 Mar, 43(3), 187 - 9
{Apnea disclosing Chlamydia trachomatis infection in a premature infant}; Zouari A et al.; The authors report a peculiar type of maternofetal Chlamydia trachomatis (CT) infection in a 34 week-premature neonate . The revealing sign was the occurrence, at age 11 days, of frequent apneas with bradycardia, needing mechanical ventilation associated with adapted antibiotic therapy for 14 days . Diagnosis was confirmed by the isolation of CT in tracheal secretions . Immediate evolution was favorable . Literature data are reviewed and a short epidemiological survey is reported.

Peptides, 1986 Mar-Apr, 7(2), 163 - 9
Effect of tunicamycin on biosynthesis, processing and release of proopiomelanocortin-derived peptides in the intermediate lobe of the frog Rana ridibunda; Vaudry H et al.; The intermediate lobe of the pituitary gland synthesizes a glycoprotein, proopiomelanocortin (POMC), which is cleaved by specific proteolytic enzymes to generate several hormonal peptides . The purpose of the present study was to examine the possible role of the carbohydrate moiety in the synthesis, intracellular processing and release of POMC-derived peptides in frog (Rana ridibunda) intermediate lobe cells . In vitro incorporation of {3H}-labelled glucosamine gave rise to three major radioactive products . Trypsin digestion of each of these glycopeptides gave a single glucosamine-labelled tryptic fragment with identical chromatographic characteristics . We conclude that Rana POMC is glycosylated in only one site (its gamma-MSH region) and that intracellular processing of this prohormone gives rise to smaller glycopeptides including glycosylated gamma-MSH . Treatment with the antibiotic tunicamycin (10 micrograms/ml, 6 hr) inhibited the glycosylation of POMC but did not significantly alter the neosynthesis of the peptide moiety of the precursor . Pulse-chase experiments combined with high-performance liquid chromatography analysis of the peptides derived from POMC revealed that inhibition of glycosylation by tunicamycin had no effect on the enzymatic cleavage of the precursor nor on the release of mature peptides . Thus, it is concluded that, in the frog, glycosylation of POMC has no influence on the biosynthesis, processing and release of intermediate lobe hormones.

Jpn J Antibiot, 1986 Mar, 39(3), 733 - 8
{Studies on the transfer of cefotaxime into bone marrow blood}; Iwamori H et al.; Cefotaxime (CTX) was administered in a dose of 2 g to 20 adult patients prior to orthopaedic surgery . Samples of the bone marrow blood and the forearm venous blood were collected at 30, 60, 90 and 120 minutes after the CTX administration, and the concentration of the drug in each sample was determined . The results are described below . The mean concentration of CTX transferred into the bone marrow blood was 59.7, 28.9, 14.7 and 7.2 micrograms/ml at 30, 60, 90 and 120 minutes after the CTX administration, respectively . The mean concentration of CTX in the venous blood was 84.0, 39.1, 19.0 and 13.8 micrograms/ml at 30, 60, 90 and 120 minutes after the CTX administration, respectively . The mean ratio of the CTX concentration in the bone marrow blood to that in the venous blood was 73.9%, 71.0%, 75.1% and 51.6% at 30, 60, 90, 120 minutes after the CTX administration . From the above results, CTX is considered to be a useful antibiotic if it is administered prior to orthopaedic surgery to prevent infections.

Jpn J Antibiot, 1986 Mar, 39(3), 686 - 92
{Penetration of cefoperazone into the exudate of the retroperitoneal space after (semi-)radical hysterectomy}; Nozawa S et al.; The purpose of the study was to examine the penetration of cefoperazone (CPZ) into the exudate of retroperitoneal space after (semi-)radical hysterectomy in patients with uterine carcinoma and to evaluate the suitability of its prophylactic use . Two grams of CPZ was administered by intravenous infusion over 1 hour just after the operation and the same dose was repeated every 12 hours for 3 consecutive days . The exudate was collected from the abdominal drainage for every 3 hours for measurements of hemoglobin, total protein and CPZ levels . Concentrations of CPZ in exudate samples were found to remain above the MICs for major causative organisms of the inflammation in both groups of patients of radical (14 cases) and semiradical (5 cases) hysterectomy . On the operative and 1st days, exudate CPZ level in the group of semiradical hysterectomy patients showed higher than that in the group of radical hysterectomy patients . But on the 2nd day, there was no significant difference in exudate CPZ level between these 2 groups . The above results indicated that the presence of blood in the retroperitoneal space might affect the concentration of the antibiotic in the exudate . From these findings, it is concluded that the present dosage regimen is efficient to prevent the postoperative infection after (semi-)radical hysterectomy.

Biometrics, 1986 Mar, 42(1), 90 - 108
A sequential test for comparing two infection rates in a randomized clinical trial, and incorporation of data accumulated after stopping; Samuel-Cahn E et al.; A randomized sequential test is considered for deciding whether prophylactic antibiotic is successful in reducing infection rates following neurosurgical operations . The test is of the curtailed "gambler's ruin" type . Its operating characteristics are obtained and tabulated, and the actual medical experiment is described in some detail . The problem of how additional accumulated data, observed after stopping, due to delayed response, should be incorporated in evaluation of sequential P-values and confidence intervals is also considered.

Antibiot Med Biotekhnol, 1986 Mar, 31(3), 185 - 9
{Effect of levorin and its combination with a modifying factor on lipid peroxidation in Crithidia oncopelti}; Chuenkova MV et al.; It was shown earlier by the authors that in the presence of sodium acetate as a modifier of C . oncopelti reaction to levorin, a polyenic antibiotic sensitivity of this organism to the antibiotic increased . At the same time there were observed changes in the ratio of the lipids and fatty acids of the total lipid fraction of C . oncopelti . The changes in the lipid composition of the biological membranes influenced lipid peroxidation (LPO) . The present paper deals with investigation of interrelation between increasing of C . oncopelti sensitivity to levorin in the presence of sodium acetate and LPO levels . Accumulation of the primary, secondary and final LPO products in C . oncopelti under the effect of sodium acetate, levorin (1 microgram/ml) added simultaneously with the modifier and levorin in a concentration of 10 micrograms/ml was investigated . It was shown that sodium acetate did not induce accumulation of LPO products as compared to the initial culture . Levorin added simultaneously with sodium acetate and levorin in a concentration of 10 micrograms/ml induced an increase in the content of LPO products in the C . oncopelti lipids . The causes of the LPO rate increase in the presence of the polyenic antibiotic are discussed.

Postgrad Med J, 1986 Mar, 62(725), 187 - 91
Record linkage study of hypokalaemia in hospitalized patients; Paice BJ et al.; Retrospective analysis of biochemical data from 58,167 hospital inpatients revealed that 21% developed hypokalaemia during hospitalization-in 5.2% the serum potassium was less than 3.0 mmol/l . Subsequent evaluation showed a positive correlation between hypokalaemia and both female sex and hospital mortality . Patients with leukaemia and lymphoid tumours, especially when receiving antibiotic or cytotoxic therapy, and patients with gastro-intestinal malignancy were amongst those most frequently experiencing hypokalaemia . There was no significant association with cardiovascular disease . Drug and intravenous fluid administration accounted for the hypokalaemia in 56% of patients . While drug-related hypokalaemia was most commonly seen with diuretics, it was also apparent following use of steroids, insulin and haematinics.

Biochem Int, 1986 Mar, 12(3), 485 - 91
Cell-free biosynthesis of arphamenine A; Okuyama A et al.; Arphamenine A was synthesized in a cell-free system obtained from the arphamenine-producing strain, Chromobacterium violaceum BMG361-CF4 . L-{14C}-phenylalanine was converted to beta-phenylpyruvic acid by phenylalanine amino-transferase obtained from the 10,000 x g supernatant (S10 fraction) . {14C}-Benzylmalic acid was synthesized from beta-phenylpyruvic acid with {14C}-acetyl-CoA in the S10 fraction . {14C}-Benzylsuccinic acid was formed from beta-phenylpyruvic acid with {14C}-acetyl-CoA and ATP in this fraction, as was {14C}-arphamenine A from benzylsuccinic acid and L-{14C}-arginine . Thus, the pathway of arphamenine A biosynthesis was confirmed by the cell-free biosynthesis of this antibiotic.

Acta Otolaryngol, 1986 Mar-Apr, 101(3-4), 242 - 6
The ototoxicity of repetitive chronic aminoglycoside administration . An experimental study; McDowell B; To determine whether previous exposure to an aminoglycoside antibiotic would predispose an individual to more severe ototoxic reactions upon subsequent administration, guinea pigs were given up to three courses of gentamicin at a dose of 50 or 100 mg/kg . Each course was separated by a period of 4 weeks, and animals were killed 4 weeks after the date of last injection . Cochlear pathology was assessed by the surface preparation technique and phase contrast microscopy . Detailed counts of sensory hair cell populations were recorded and statistically analysed . No significant ototoxic hair cell loss occurred following the repetition of 50 mg/kg . At 100 mg/kg, repetitive administration produced a significant and cumulative destruction of the most basal outer and inner hair cells . Using this protocol, it was concluded that if the initial exposure proved ototoxic, further administration of gentamicin increased subsequent sensory hair cell loss.

J Assoc Off Anal Chem, 1986 Mar-Apr, 69(2), 188 - 90
Indirect spectrophotometric method for determining epicillin; Nunez-Vergara LJ et al.; A new UV spectrophotometric assay for determination of epicillin in capsules and plasma is reported . The method is based on the absorptivity of a degradation product obtained from the acidic hydrolysis of the antibiotic . The isolation, identification, individual capsule assays, composite assay, and recovery studies are described . Also, the proposed method is compared with a dc polarographic assay in plasma.

Can Anaesth Soc J, 1986 Mar, 33(2), 222 - 6
Iatrogenic oesophageal perforation due to tracheal or nasogastric intubation; Norman EA et al.; Oesophageal perforation, due to a difficult endotracheal or nasogastric intubation occurred in a 49-year-old female . Perforation of the oesophagus is a rare complication of intubation of the trachea or oesophagus . Endotracheal intubation alone is most often blamed for iatrogenic oesophageal trauma following surgery . The incidence of iatrogenic oesophageal trauma is similar after nasogastric or endotracheal intubation . Iatrogenic oesophageal perforation occurs principally over the cricopharyngeus muscle on the posterior wall of the oesophagus . Here the oesophagus is thin and is markedly narrowed . Contamination of the perioesophageal space with gastric contents leads to diffuse cellulitis and infection . Diagnosis is made by evidence of cervical subcutaneous emphysema, cervical pain, dysphagia, temperature elevation and leukocytosis . Plain roentenograms of the neck and a contrast media swallow will confirm the diagnosis . Treatment consists of massive antibiotic therapy followed by surgical repair and drainage of the area . Mortality ranges from 10-15 per cent with early diagnosis to 50 per cent if surgery is delayed.

Ital J Orthop Traumatol, 1986 Mar, 12(1), 77 - 83
Ultrasonography in the investigation of loose hip prostheses; Baratelli M et al.; Twenty-two patients with severe pain in the hip on weight-bearing after prosthetic replacement were investigated by radiography, arthrography, scintigraphy and ultrasonography to determine the accuracy of these diagnostic methods in detecting loosening of infective or mechanical origin . In two cases, ultrasonography revealed superficial infections that were resolved with antibiotic therapy . Of the remaining 20 cases, 12 involved a deep infection and in 8 the loosening was of mechanical origin . In the deep infections, standard radiography provided a diagnosis in 66% of cases, arthrography in 75% and scintigraphy in 83%, while ultrasonography detected the deep infection in all 12 cases . In the patients with mechanical mobilization, arthrography and ultrasonography were 100% accurate . Since ultrasonography is able to detect discrete or diffuse lesion of the soft tissues around a prosthesis it should be included among the methods used to screen patients with painful hips after prosthetic replacement.

Arch Microbiol, 1986 Mar, 144(2), 181 - 6
LD-carboxypeptidase activity in Escherichia coli . II . Isolation, purification and characterization of the enzyme from E . coli K 12; Metz R et al.; A LD-carboxypeptidase from Escherichia coli K 12 was isolated by Tris-EDTA treatment and purified to electrophoretic homogeneity by DEAE-cellulose chromatography . The enzyme has a molecular weight of approximately 12,000 as determined by sodium dodecyl sulfate-polyacrylamide electrophoresis and by Sephadex G-100 gel filtration . The studies of the substrate specificity of the enzyme revealed that UDP-MurNAc-tetrapeptide is a superior substrate, with a Km value of 1 X 10(-4) mol/l . The activity of the LD-carboxypeptidase was inhibited by D-amino acids and the beta-lactam antibiotic nocardicin A . Ki values of 0.3 and 43 mmol/l were determined for nocardicin A and D-homoserine, respectively . The properties of the purified enzyme correspond to activity I in ether treated cells.

Arch Microbiol, 1986 Mar, 144(2), 175 - 80
LD-carboxypeptidase activity in Escherichia coli . I . The LD-carboxypeptidase activity in ether treated cells; Metz R et al.; The activities of the LD-carboxypeptidases of Escherichia coli K 12 and of a mutant strain 155 with reduced activities were studied with the aid of ether treated cells . Evidence was obtained that was consistent with the suggestion that in both strains two LD-carboxypeptidase activities are present . Activity I degrades the nucleotide activated precursor UDP-MurNAc-tetrapeptide and activity II splits off D-alanine residues from position 4 of the peptide subunits in the nascent murein . In the mutant strain activity I is reduced 10fold compared with strain K 12, whereas activity II is not affected . The two activities could be distinguished with regard to their sensitivity to D-amino acids and the beta-lactam antibiotic thienamycin.

No Shinkei Geka, 1986 Mar, 14(4), 571 - 6
{A case of cerebral aspergilloma following radical operation of a cerebral aneurysm}; Morinaga K et al.; A case of aspergillotic abscess with granuloma is reported . A 45-year-old man was admitted to our hospital on Apr . 10, 1984 due to the rupture of an aneurysm of the anterior communicating artery . Neck clipping of the aneurysm was proposed on Apr . 12, 1984, but was not performed because of cardiac arrest with unknown etiology during the operation . Neck clipping was performed on Apr . 23, 1984 . Antibiotic therapy was prolonged for about three weeks . About 6 months after surgery, he was readmitted on Oct . 12, 1984 with the chief complaint of general fatigue and headache . On readmission, laboratory examinations were normal except for leukocytosis, elevated ESR and positive CRP . Neurological examination revealed left papilledema, disorientation and memory disturbance . On lumbar puncture, the cerebrospinal fluid showed 2 lymphocytes, 71 mg percent protein, 94 mg percent glucose . The skull and chest X-ray findings were normal . The CT scan revealed an irregular low density area in the left frontal lobe with abnormal enhancement . Steroids and antibiotic therapy were initiated . Since mass signs on CT scan increased gradually, partial removal of abscess and granuloma was performed on Nov . 5, 1984 . From the necrotic granuloma, Aspergillus was microscopically recognized and Aspergillus fumigatus was cultured on Sabouraud's medium . Immunologically, serum immunoglobulin levels and the subset of lymphocytes were normal . Tuberculin reaction was negative . After the operation, amphotericin-B and 5-fluorocytosine (5-FC) were administered . Nevertheless mass signs on CT scan increased again . The fourth operation was performed on Dec . 6, 1984.(ABSTRACT TRUNCATED AT 250 WORDS)

Tohoku J Exp Med, 1986 Mar, 148(3), 333 - 4
cis-Diamminedichloroplatinum (CDDP)-fosfomycin (FOM) combination in lung cancer patients with respect to the peripheral T lymphocyte subsets; Kumano N et al.; An antibiotic FOM was found to be preventive of the side effect of an antineoplastic drug CDDP on the peripheral T lymphocytes in lung cancer patients . Whereas finding a significant decrease in T3+ cells (p less than 0.01) and T4+ subset (p less than 0.05) with CDDP alone, the initial levels of these cell populations were kept unchanged in combination with FOM . T8+ subset showed no substantial change . A protective effect of FOM on T4+ subset was suggested to be an additional aspect of its action at least in combination with CDDP.

J Bacteriol, 1986 Mar, 165(3), 871 - 7
Plasmid inheritability and biomass production: comparison between free and immobilized cell cultures of Escherichia coli BZ18(pTG201) without selection pressure; de Taxis du Poet P et al.; Maintenance of the plasmid pTG201 in Escherichia coli BZ18 was studied for both free and immobilized cells during chemostat culture, in the absence of the antibiotic against which resistance was plasmid encoded . Electron microscopic observations of immobilized proliferant cells within carrageenan gel beads showed high cell concentrations and growth into distinct cavities . The plasmid which coded for the catechol 2,3-dioxygenase activity was stably maintained during 80 generations in the case of immobilized cells . A theoretical analysis founded on the compartmentalization resulting from the immobilized growth conditions was described . However, the model still showed a plasmid stability inferior to that determined experimentally . Hypotheses dealing with physiological changes of immobilized cells were presented . In addition, the high cell concentrations obtained in the outer 50 microns of the carrageenan gel beads gave a biomass productivity within this useful volume which was 20 times higher than in free-cell cultures.

Rev Med Interne, 1986 Mar, 7(2), 185 - 95
{Pharmacokinetic behavior of pefloxacin in man}; Fourtillan JB; The pharmacokinetic profile of pefloxacin is one of the major assets of this new antibiotic of the quinolone family . Digestive absorption is rapid and complete after oral administration . The pharmacokinetic pattern is the same with both routes . The high apparent volume of distribution (AVD = 117 +/- 6 litres) reflects good diffusion in extravascular compartments . Pefloxacin can therefore be used not only for the treatment of systemic infections, but also for that of extravascular infections, whatever the perfusion rate of the infected organ . The predominant route of excretion of pefloxacin is extrarenal, after hepatic degradation; it is responsible for prolonged elimination half-life in patients with hepatic insufficiency . Since renal excretion of the unchanged drug is less important, there is no need to modify the dosage in case of renal impairment . When pefloxacin is eliminated by biotransformation, it is excreted slowly, and plasma or tissue levels of its unchanged form remain much higher . In subjects with normal liver function, the mean elimination half-life is almost 12 h, which makes it possible to administer pefloxacin twice a day . During treatment with 400 mg doses, the steady state is reached within 48 h; mean peak plasma concentrations then are 10 micrograms X ml-1 and mean trough concentrations 4 micrograms X ml-1 . The pharmacokinetic properties of pefloxacin give this antibiotic an unquestionable advantage over third-generation cephalosporins and aminoglycosides.

Proc Natl Acad Sci U S A, 1986 Mar, 83(5), 1276 - 80
A mammalian high mobility group protein recognizes any stretch of six A.T base pairs in duplex DNA; Solomon MJ et al.; alpha-Protein is a high mobility group protein originally purified from African green monkey cells based on its affinity for the 172-base-pair repeat of monkey alpha-satellite DNA . We have used DNase I footprinting to identify 50 alpha-protein binding sites on simian virus 40 DNA and thereby to determine the DNA binding specificity of this mammalian nuclear protein . alpha-Protein binds with approximately equal affinity to any run of six or more A X T base pairs in duplex DNA, to many, if not all, runs of five A X T base pairs, and to a small number of other sequences within otherwise (A + T)-rich regions . Unlike well characterized sequence-specific DNA binding proteins such as bacterial repressors, alpha-protein makes extensive contacts within the minor groove of B-DNA . These and related findings indicate that, rather than binding to a few specific DNA sequences, alpha-protein recognizes a configuration of the minor groove characteristic of short runs of A X T base pairs . We discuss possible functions of alpha-protein and the similarities in DNA recognition by alpha-protein and the antibiotic netropsin.

Southeast Asian J Trop Med Public Health, 1986 Mar, 17(1), 119 - 24
Two to three days treatment of typhoid fever with ceftriaxone; Lan CK et al.; Pharmacokinetic properties of ceftriaxone, such as sustained tissue drug levels over 24 hours after a single injection; good penetration of the antibiotic into cells; significant biliary excretion as active unchanged compound and high potency against S . typhi, should make it possible to significantly shorten the treatment of typhoid fever . To test this hypothesis a pilot, open study was initiated . 17 adult patients suffering from uncomplicated typhoid or paratyphoid fever, documented by blood culture, were treated with 4g ceftriaxone once daily for three days (4 patients) or two days (15 patients) . The cure rate of 17 assessable patients was 94.2% (one failure) . One possible relapse was observed two months after treatment . It is to be noted that no patient in the study suffered from a severe form of the disease.

J Bacteriol, 1986 Mar, 165(3), 964 - 71
Stable transformation of the cyanobacterium Synechocystis sp . PCC 6803 induced by UV irradiation; Dzelzkalns VA et al.; Irradiation of the photoheterotrophic cyanobacterium Synechocystis sp . PCC 6803 with low levels of UV light allows for stable, integrative transformation of these cells by heterologous DNA . In this system, transformation does not rely on an autonomously replicating plasmid and is independent of homologous recombination . Cells treated with UV light in the absence of DNA and cells given DNA but not exposed to UV do not yield antibiotic-resistant colonies in platings of up to 2 X 10(8) cells . Optimal conditions for this UV-induced transformation are described . Analysis of the transformants indicates that (i) only a segment of the introduced plasmid is found in the DNA of the transformed cells; (ii) in independently isolated clones, DNA insertion apparently occurs at different sites in the chromosome; and (iii) hybridization data suggest that insertion in one of the transformants may have occurred into a region of the chromosome that is repeated or that integration of plasmid DNA may have been accompanied by a rearrangement or duplication of DNA sequences near the insertion site . DNA isolated from the primary transformants as well as a cloned fragment containing the UV-inserted plasmid sequence and flanking cyanobacterial DNA transform wild-type cells at a high frequency (5.0 X 10(-4) and 1.5 X 10(-5), respectively) . Possible mechanisms of this transformation system are discussed, as are the potential uses of this system as an integrative cloning-complementation vector and as a mutagenic agent in which the genetic lesion is already tagged with a selectable marker.

J Antibiot (Tokyo), 1986 Mar, 39(3), 364 - 71
K-4, a novel inhibitor of angiotensin I converting enzyme produced by Actinomadura spiculosospora; Koguchi T et al.; A novel inhibitor of angiotensin I converting enzyme (ACE), named K-4, was isolated from the culture broth of Actinomadura spiculosospora nov . sp . K-4 . The K-4 was an oligopeptide containing L-phenylalanine with (R)-1-amino-2-(4-hydroxyphenyl)ethylphosphonic acid as the C-terminal residue . The compound proved to be a specific and reversible inhibitor of ACE with the inhibition constant (Ki) of 0.18 microM, and inhibited ACE non-competitively by use of hippuryl-L-histidyl-L-leucine (HHL) as a substrate . When administrated intravenously to rats, K-4 inhibited the pressor response to angiotensin I.

Ann Ophthalmol, 1986 Mar, 18(3), 95 - 6
Diffuse cutaneous hypersensitivity reaction after dexamethasone/polymyxin B/neomycin combination eyedrops; Baldinger J et al.; Localized cutaneous hypersensitivity reactions to antibiotic eyedrops are not unusual . To our knowledge, however, a diffuse cutaneous reaction to eyedrops containing dexamethasone/polymyxin B/neomycin has never been reported . We describe the diffuse skin changes noted in a 72-year-old patient five days after starting eyedrop therapy.

J Virol, 1986 Mar, 57(3), 1048 - 54
Ecotropic murine leukemia virus-induced fusion of murine cells; Pinter A et al.; Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone . The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with {3H}thymidine and fused with an unlabeled parent . This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses . Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells . Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions . Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction . The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells.

Acta Paediatr Scand, 1986 Mar, 75(2), 205 - 10
Epidemiological aspects of P-fimbriated E . coli . II . Variations in incidence of E . coli infections in children attending a neonatal ward; Tullus K et al.; In a retrospective study we found an increased incidence of E . coli septicemia and pyelonephritis among children cared for in a special neonatal ward during 1975 and 1976 compared to the following years . The study was undertaken because of a previously reported epidemic outbreak of E . coli pyelonephritis in children cared for in the same neonatal ward during 1979-1982 . The increased incidence of infections seems to be caused by spread of one or several virulent E . coli strains in the ward . Two of the strains causing septicemia were saved . They showed a multiply resistant antibiotic pattern similar to most of the strains causing pyelonephritis among the children born at that time . Their serotype was O4:K3 and they were P-fimbriated . Septicemia occurred among high-risk infants at a mean age of five days, while pyelonephritis occurred among uncomplicated cases at a mean age of 3.9 months . The proposed spread of one or several virulent E . coli strains correlates to a high bed occupancy in the ward during that time . r = 0.38 (p less than 0.01).

Gan To Kagaku Ryoho, 1986 Mar, 13(3 Pt 2), 677 - 83
{Modification of suppressor activity and effector activity of tumor-bearing hosts by bleomycin}; Hosokawa M; We investigated the immunological role of an antitumor antibiotic, bleomycin (BLM) in its therapeutic effects . BLM was found to be one of unique antitumor agents which can augment the antitumor immune responses in the tumor-bearing hosts . The evidence was provided by the following experimental results . The therapeutic effect of BLM on a transplanted rat tumor is host-mediated and administration timing-dependent . BLM eliminates suppressor cell activity induced in tumor-bearing rats and augments tumor-neutralizing activity and responsiveness of spleen cells to tumor associated antigen . BLM also activates tumoricidal activity of peritoneal macrophages of rats . Thus, it is suggested that the antitumor immune response augmented by BLM plays an important role in the therapeutic effects of BLM.

Rofo, 1986 Mar, 144(3), 267 - 72
{Experiences with preoperative and palliative percutaneous transhepatic cholangio-drainage}; Arlart IP et al.; In obstructive jaundice PTCD plays an important role as a preoperative or a palliative therapeutic method inspite of the availability of biliary endoprostheses . This study was carried out to assess complications following PTCD, the effect on liver function (serum parameters) and the relationship between duration of preoperative drainage and postoperative complication rate . The results demonstrate that 11-hole pigtail-catheters are useful for intrahepatic location and 32-hole ringcatheters for extrahepatic location due to reduced dislocation rates . The effect of biliary drainage after 7 rsp . 25 days on liver function was significant (p less than 0.05) . As a main complication fever episodes could be observed associated with pathologic bile-/bloodcultures in most cases; other complications were similar to those presented in the literature . A prophylactic antibiotic therapy following PTCD seems to be useful, a preoperative biliary drainage is recommended until serum bilirubin levels become constant or at least for 2 weeks.

Am J Kidney Dis, 1986 Mar, 7(3), 245 - 9
A Bartter's-like syndrome from capreomycin, and a similar gentamicin tubulopathy; Steiner RW et al.; Marked renal potassium and magnesium wasting, alkalosis, and a progressive increase in plasma renin and eventual hyperaldosteronemia developed during a 15-month course of in-hospital capreomycin therapy that was necessary for drug-resistant pulmonary tuberculosis . A prominent feature of the present case was renal chloride wasting, a feature of the capreomycin syndrome that has previously received little attention . Similar potentially life-threatening metabolic abnormalities, which resemble those found in Bartter's syndrome, can occur during prolonged therapy with the antibiotic gentamicin . In the present case, electrolyte abnormalities were unaffected by three days of indomethacin therapy but were partially corrected by large doses of spironolactone . Capreomycin, viomycin (an antibiotic closely related to capreomycin), and gentamicin are highly basic polypeptide antibiotics that may induce strikingly similar and potentially fatal syndromes of renal tubular dysfunction that can feature multiple electrolyte abnormalities.

Biochem Biophys Res Commun, 1986 Feb 26, 135(1), 330 - 5
Prevention of doxorubicin-induced killing of MCF-7 human breast cancer cells by oxygen radical scavengers and iron chelating agents; Doroshow JH; This study investigated the effect of oxygen radical scavengers and iron chelating agents on the toxicity of doxorubicin for MCF-7 human breast cancer cells . Superoxide dismutase and catalase, but not the heat-inactivated enzymes, the hydroxyl radical scavenger N-acetylcysteine, and the organoselenium compound 2-phenyl-1-2-benzisoselenazol-3(2H)-one, which possesses glutathione peroxidase-like activity, significantly reduced or abolished tumor cell killing by doxorubicin . Similar protective activity was found only for those iron chelating agents capable of penetrating the tumor cell plasma membrane . These experiments suggest that an iron-dependent oxygen radical cascade contributes to the antineoplastic action of the anthracycline antibiotic doxorubicin.

Biochemistry, 1986 Feb 25, 25(4), 775 - 80
Mucidin and strobilurin A are identical and inhibit electron transfer in the cytochrome bc1 complex of the mitochondrial respiratory chain at the same site as myxothiazol; Von Jagow G et al.; Mucidin and strobilurin A, antifungal antibiotics isolated from the basidiomycetes Oudemansiella mucida and Strobiluris tenacellus, respectively, inhibit electron-transfer reactions in the cytochrome bc1 complex of the mitochondrial respiratory chain . The two compounds have identical effects on oxidation-reduction reactions of the cytochromes b and c1 in isolated succinate-cytochrome c reductase . They inhibit reduction of cytochrome c1 by succinate but do not inhibit reduction of cytochrome b . When added in combination with antimycin, either inhibitor blocks reduction of both cytochromes b and c1 . Mucidin and strobilurin A differ from antimycin in that they inhibit, rather than promote, oxidant-induced reduction of cytochrome b . They also differ from antimycin in that they do not block reduction of cytochrome b by succinate when cytochrome c1 is previously reduced by ascorbate and they do not inhibit oxidation of cytochrome b by fumarate . These effects of mucidin and strobilurin A are, however, qualitatively identical with those of myxothiazol, an antibiotic that inhibits respiration by binding to cytochrome b {Von Jagow, G., Ljungdahl, P . O., Graf, P., Ohnishi, T., & Trumpower, B . L . (1984) J . Biol . Chem . 259, 6319-6326} . Mucidin and strobilurin A have identical UV and mass spectra, and they elute together on high-pressure liquid chromatography . We thus conclude that these antibiotics, although isolated from different bacteria, are structurally identical . Our results indicate that strobilurin A and mucidin inhibit electron transport at the same site as myxothiazol and not at the antimycin site, as previously reported {Subik, J., Behren, M., & Musilek, V . (1974) Biochem . Biophys . Res . Commun . 57, 17-22}.

J Chromatogr, 1986 Feb 21, 352, 445 - 53
High-performance liquid chromatographic screening and confirmation methods for chloramphenicol residues in meat with off-line cartridge sample clean-up and on-line diode array UV-VIS detection; Keukens HJ et al.; Two high-performance liquid chromatography (HPLC) methods for the analysis and confirmation of residues of the antibiotic chloramphenicol in edible animal tissues are described . The first method consists of an aqueous extraction followed by purification through an Extrelut cartridge and toluene partition . With this simple and rapid method, meat samples can be screened at the 5 micrograms/kg level . The second, more comprehensive, method is based on ethyl acetate extraction, followed by purification through a silica Sep-Pak cartridge and partition with buffer-diethyl ether and water-toluene . Confirmation of positive peaks at the 10 micrograms/kg level is performed by diode array UV-VIS detection . The recoveries for the two methods at the 10 micrograms/kg level are 58 and 85% respectively, coefficients of variation 5-6% . With the confirmation method, glucuronide and sulphate conjugates can be determined . However, in a positive reference sample (pig) none was observed.

J Chromatogr, 1986 Feb 21, 352, 369 - 79
Drug monitoring by a fully automated high-performance liquid chromatographic technique, involving direct injection of plasma; Takahagi H et al.; A procedure involving direct injection of whole plasma for analyses of drugs by an automated high-performance liquid chromatograph was developed . This system comprised two columns, two pumps, one detector, two programmable switching valves, an automatic sample injector with a cooling device for sample tubes and a microprocessor . Effluents from the first column, containing a drug of interest, were selectively introduced into the second column for further separation . The columns used were an aqueous gel chromatography column (column 1) and an ODS column (column 2) . The solvent for column 1 must be weaker than that for column 2, so that the solutes from the former will be enriched at the top of the latter . The validity and applicability of this procedure for the study of drug metabolism were demonstrated with the antibiotic cefmetazole, the anticoagulant warfarin, the antitumour agent carboquone and the anaesthetic ketamine.

Med J Aust, 1986 Feb 17, 144(4), 205 - 11
Drug interactions with oral contraceptive preparations; Shenfield GM; PIP: Oral contraceptives (OCs) should be used with additional caution in combination with other drugs in certain disease states . This discussion focuses on only those interactions which are due to identifiable pharmacokinetic processes . Pharmacological interactions between OCs and other compounds may be of 2 kinds: drugs may impair the effectiveness of the OCs to cause breakthrough bleeding or to allow pregnancy to occur; and OCs may interfere with the metabolism of other componds . In general, interactions of the 1st kind are due to interference with the absorption, metabolism, or excretion of estrogens, and interactions of the 2nd kind are due to competition for metabolic pathways . It is difficult to obtain estimates of the frequency of interactions, but it seems likely that, as low-dose preparations become more widely used, interactions of the 1st type will become more common and those of the 2nd type less common . Although it is probably only those women with low plasma hormone concentrations who are at risk that other drugs may interfere with contraceptive efficacy, and women with high plasma concentrations of estrogen who are at risk of side-effects and that OCs may interfere with other drugs, there is no way of detecting women in either category . Consequently, it is safer for the present to assuume that all women who take OCs might be at risk of some form of interaction . Significant drug interactions in which contraceptive efficacy is reduced are more likely to occur in the early part of the cycle when circulating hormone concentrations are of critical importance . It is well known that infective diarrhea can induce OC failure by increasing gastrointestinal motility and reducing hormone absorption . Thus, any drug which reduces gut transit time and causes diarrhea is potentially likely to reduce circulating concentrations of OCs . The sulphation of ethinl-estradiol in the gastrointestinal wall has been shown to be a site of interaction for the enhancement of the activity of OCs . Ascorbic acid also undergoes sulphate conjugation in the gut wall and acts as a competitive inhibitor for sulphation of estrogens . The most clinically significant group of interactions occurs with other drugs that are metabolized by the same hepatic microsomal pathways as is estrogen . Most of the anticonvulsant drugs are inducers of microsomal enzymes . Rifampicin is known to be a potent inducer of hepatic microsomal enzymes and has been shown to increase the rate of metabolism of both estrogeens and progestogens . A recent report has suggested that the antifugal drug griseofulvin may cause a clinically important interaction with OCs . There are numerous well documented clinical reports of women who have taken OCs without missing a dose who have become pregnant while taking a variety of antibiotic agents such as ampicllin and tetracycline . Estrogens are inhibitors of hepatic microsomal enzymes . In this way they may show the metabolsim of other drugs, thus increasing their plasma and tissue concentrations and increasing the risk of side-effects . These interactions might be expected to become less common as the concentration of estrogen in OCS decreases .

Am J Cardiol, 1986 Feb 15, 57(6), 413 - 8
Contribution of echocardiography and immediate surgery to the management of severe aortic regurgitation from active infective endocarditis; Sareli P et al.; The timing of surgery in patients with severe aortic regurgitation and left ventricular (LV) failure, particularly when associated with active infective endocarditis (IE), is of the utmost importance . From July 1982 to May 1984, 34 patients, aged 15 to 60 years, with severe aortic regurgitation underwent immediate (within 24 hours of diagnosis) aortic valve surgery . All patients were in New York Heart Association class IV for LV failure . Eighteen patients had right-sided heart failure . Decision for immediate surgery was based on the echocardiographic demonstration of diastolic closure of the mitral valve or of vegetations on the aortic valve . Premature closure of the mitral valve was demonstrated echocardiographically in 17 patients, 13 of whom had diastolic crossover of LV and left atrial pressure tracings recorded at surgery . IE of the aortic valve was confirmed at surgery in 29 patients, 27 of whom had vegetations on echocardiography . Seven patients required replacement of both aortic and mitral valves . Antibiotic therapy for IE was started immediately after blood cultures were taken and continued for 4 to 6 weeks postoperatively . The mortality rate within 30 days of surgery was 6% for the group as a whole and 7% for those with IE . Mean follow-up period for the 32 survivors was 10.6 months . There were 2 late deaths . No patient had periprosthetic regurgitation or persistence of endocarditis . Procrastination in referral for surgery of these extremely ill patients is not justified and is likely to be associated with higher risks of morbidity and mortality.

Int J Clin Pharmacol Ther Toxicol, 1986 Feb, 24(2), 88 - 92
Clinical pharmacokinetics of theophylline during co-treatment with cefaclor; Jonkman JH et al.; The effect of cefaclor on the steady state pharmacokinetics of theophylline was investigated in healthy young adults by comparing the pharmacokinetic parameters as found during a nine days course of theophylline alone and as obtained during co-medication with the antibiotic cefaclor . The pharmacokinetic parameters obtained on Day 9 during the two periods of drug treatment accounted for the following figures respectively: minimum plasma concentration 5.0 +/- 1.7 mg X 1(-1) (mean +/- SD) and 6.0 +/- 2.0 mg X 1(-1); maximum plasma concentration 9.7 +/- 2.6 mg X 1(-1) and 9.0 +/- 2.6 mg X 1(-1); time to peak 3.2 +/- 0.4 h and 3.9 +/- 0.8 h; AUC 132.54 +/- 41.73 mg X 1(-1) X h and 126.90 +/- 40.45 mg X 1(-1) X h; half-life of elimination 6.6 +/- 1.6 h and 7.1 +/- 1.2 h; clearance 0.059 +/- 0.011 1 X h-1 X kg-1 and 0.063 +/- 0.014 1 X h-1 X kg-1; volume of distribution 0.54 +/- 0.09 1 X kg-1 and 0.64 +/- 0.17 1 X kg-1 . Only the values for cmax and tmax after cefaclor co-treatment were slightly, but significantly (p less than 0.05) different from the values found after administration of theophylline alone . As the volume of distribution and the clearance were not affected by cefaclor, it is concluded that both drugs can be given concomitantly without any dosage adjustment of theophylline.

J Am Acad Dermatol, 1986 Feb, 14(2 Pt 2), 361 - 7
Necrotizing fasciitis associated with porphyria cutanea tarda; Kranz KR et al.; A case is presented of a 31-year-old white woman with necrotizing fasciitis . She had had a previous diagnosis of porphyria cutanea tarda that was manifested in part by bullous lesions on her forearms and hands . A soft tissue infection developed in her left hand and forearm in an area of bullous disease . After a delay of 8 days the diagnosis of necrotizing fasciitis was made . She recovered following surgical debridement, extensive fasciotomy, broad-spectrum antibiotic coverage, and hyperbaric oxygen therapy.

South Med J, 1986 Feb, 79(2), 255 - 6
Piperacillin-induced anemia and leukopenia; Bressler RB et al.; Piperacillin is being used with increasing frequency as an important antibiotic for the treatment of severe and life-threatening infections . Many of these patients may have multiple possible causes of leukopenia and/or anemia . An awareness of the potential for piperacillin to cause the rapid onset of leukopenia and/or anemia may have important therapeutic implications, especially in severely ill patients.

Postgrad Med, 1986 Feb 1, 79(2), 287 - 94
Fever following abdominal surgery . Unusual infectious causes; Gleckman RA et al.; Identification of the cause and subsequent specific therapy are indicated for those prolonged or relapsing fevers that follow abdominal surgery . On rare occasions, these fevers can be attributed to potentially life-threatening occult infections, including maxillary sinusitis, acute cholecystitis, antibiotic-related pseudomembranous colitis, toxic shock syndrome, systemic candidiasis, and transfusion-related cytomegalovirus disease, malaria, and babesiosis . Early recognition and appropriate treatment of these infections relieve anxiety, reduce hospital costs, and increase patient survival rates.

Postgrad Med, 1986 Feb 1, 79(2), 111 - 9
Septic arthritis . Clinical approach to the 'hot joint'; Evanchick CE et al.; Joint space infections continue to be among the most common forms of arthritis . Diagnosis can be difficult, particularly in the presence of underlying joint disease . Septic arthritis should be suspected in all patients who present with an acutely swollen joint . Immediate joint aspiration with Gram's stain and culture of the synovial fluid is essential . Intensive, long-term antibiotic therapy is necessary to prevent a high rate of morbidity and, possibly, death.

J Clin Invest, 1986 Feb, 77(2), 405 - 15
Isolation and study of an acquired inhibitor of human coagulation factor V; Nesheim ME et al.; A coagulation Factor V inhibitor developed in a man 75 yr of age in association with an anaplastic malignancy and drug treatment (including the aminoglycoside antibiotic, gentamicin) . The patient did not bleed abnormally, despite both surgical challenge and plasma Factor V activity of less than 1% . The inhibited plasma had grossly prolonged prothrombin and activated partial thromboplastin times, but a normal thrombin time . Mixing studies indicated progressive coagulation inhibition with normal plasma, but not with Factor V-deficient plasma, and reversal of coagulation inhibition by the addition of bovine Factor V to the patient's plasma . 1 ml of patient plasma inhibited the Factor V activity of 90 ml of normal human plasma . The inhibitor was isolated by sequential affinity chromatography on protein A-Sepharose and Factor V-Sepharose . The IgG isolate markedly inhibits the activity of prothrombinase assembled from purified Factors Xa and Va, calcium ion, and phospholipid vesicles, and partially inhibits prothrombinase assembled from purified Factor Xa, calcium ion, and normal platelets . The Factor V of platelets, however, appears relatively inaccessible to the antibody, inasmuch as platelets isolated from whole blood supplemented for 8 h with the antibody functioned normally with respect to platelet Factor V-mediated prothrombinase function . The absence of obvious hemorrhagic difficulties in the patient, the total inhibition of plasma Factor V by the inhibitor, and the apparent inaccessibility of platelet Factor V to the inhibitor specifically implicate platelet Factor V in the maintenance of hemostasis.

J Bone Joint Surg Am, 1986 Feb, 68(2), 281 - 7
The effect of centrifugation on the fracture properties of acrylic bone cements; Rimnac CM et al.; In this study, centrifugation did not alter the static or cyclic fracture properties of bone cement . Tests of fracture toughness and fatigue-crack propagation of centrifuged specimens of commercial cements (with and without antibiotic additions) demonstrated no significant difference from control values . Among the cements tested, Palacos (with and without antibiotic) was found to have a significantly higher fracture toughness than either Simplex or Zimmer . We attributed this difference in fracture toughness to the higher molecular weight measured for the Palacos cements . For the tested cements, only Simplex had a significantly greater volume contraction on setting due to centrifugation . The results of our study demonstrate that centrifugation of bone cement does not improve the cement's resistance to fracture in the presence of surface imperfections, such as those found at the bone-cement interface.

Exp Hematol, 1986 Feb, 14(2), 156 - 61
Stimulation of human committed bone marrow stem cells (CFU-GM) by chloramphenicol; Bostrom B et al.; Chloramphenicol, an antibiotic associated with reversible bone marrow suppression and fatal aplastic anemia, was found to increase human bone marrow granulocyte-macrophage colonies (CFU-GM) in vitro . Maximal stimulation was at a concentration of 1.0 micrograms/ml (3.1 microM), with inhibition at concentrations greater than 10 micrograms/ml . This effect was noted in normal donors and in children with neutropenia of various etiologies . Stimulation was ablated by depletion of bone-marrow-adherent cells and was restored by addition of peripheral-blood-adherent mononuclear cells . The stimulatory effect appears to be specific for chloramphenicol, as numerous structural analogues of chloramphenicol, including its three stereoisomers, did not show stimulation . The stimulation was present at plateau concentrations of colony-stimulating activity, suggesting that the stimulatory effect is not due to elaboration of excess colony-stimulating activity by chloramphenicol . We hypothesize that low concentrations of chloramphenicol stimulate CFU-GM by a highly specific interaction with adherent mononuclear cells and elaboration of an undefined growth factor.

Am J Dis Child, 1986 Feb, 140(2), 147 - 50
Suppression of carbon monoxide excretion rate by tin protoporphyrin; Posselt AM et al.; The effect of a single prophylactic dose of tin protoporphyrin on the carbon monoxide (CO) excretion rate of antibiotic-treated neonatal rats before and after hematoma formation was evaluated . The CO excretion rate, reflecting the rate of bilirubin production, of tin protoporphyrin-treated (TP-H) rats 24 hours after injection of 65 mole of tin protoporphyrin per kilogram (time {t} = 0 hours) was approximately 18% lower than those of the saline-control (S-C) and saline-hematoma (S-H) rats, but this difference was no longer evident at t = 43 hours . After hematoma formation at t = 44 hours, the CO excretion rate of the S-H rats increased rapidly; this increase was delayed and lessened in the TP-H rats . At eight hours posthematoma (t = 52 hours), the CO excretion rate of the TP-H rats was significantly lower than that of the S-H rats, 53 +/- 2 vs 73 +/- 3 microL/kg/hr, respectively . A maximal rate of 89 +/- 5 microL/kg/hr was reached 25 hours posthematoma in the S-H rats (t = 69 hours), as compared with 80 +/- 3 microL/kg/hr at 44 hours posthematoma in the TP-H rats (t = 88 hours) . The recovery of injected blood as CO over a 68-hour study period was approximately 90% for the S-H rats and approximately 65% for the TP-H rats . At t = 112 hours, hepatic heme oxygenase activity of the TP-H rats was still significantly lower than that of the S-H and S-C rats; however, plasma bilirubin concentrations of all three groups were similar . These studies demonstrate that tin protoporphyrin is an effective in vivo inhibitor of endogenous heme catabolism as measured by the CO excretion rate in antibiotic-treated neonatal rats with and without artificially created hematomas.

Q J Med, 1986 Feb, 58(226), 123 - 32
Persistent infection as a cause of renal disease in patients submitted to renal biopsy: a report from the Glomerulonephritis Registry of the United Kingdom MRC; Jones JM et al.; We report the results of a survey within the United Kingdom of the importance of persistent systemic infection in patients with unexplained renal disease who undergo renal biopsy . Twenty-two units participated . Overall 1.7 per cent of patients undergoing biopsy had an infection but there was large variation between units . Interstitial nephritis and amyloid deposits were more common in patients with infection, and minimal change nephropathy was less common than in patients undergoing biopsy but without infection . The respiratory tract was the most common site of infection but was rarely associated with glomerulonephritis of which the most common cause was infective endocarditis . Drug treatment may have caused the renal lesion in 16 per cent of patients . Amyloid deposits, present in 13.6 per cent of patients, was the most common cause of progressive renal failure . Most other patients had some improvement in renal function once the putative cause, whether infection or antibiotic, was removed.

J Gen Microbiol, 1986 Feb, 132 ( Pt 2), 299 - 305
A decrease in GTP content is associated with aerial mycelium formation in Streptomyces MA406-A-1; Ochi K; Aerial mycelium formation by Streptomyces sp . MA406-A-1, a formycin-producing strain, was suppressed by the presence of excess nutrient . In such suppressed cultures, decoyinine, which specifically inhibits GMP synthetase, initiated the formation of aerial mycelium at concentrations which only partially inhibited growth . The intracellular GTP pool of organisms growing in liquid culture markedly decreased on the addition of decoyinine . Decoyinine was also effective in initiating aerial mycelium formation of three other Streptomyces spp . examined . Regardless of the successful initiation of aerial mycelium formation, the ability of the cells to produce antibiotics (formycin or actinomycin D) did not increase, but decreased, on the addition of decoyinine . It is concluded that aerial mycelium formation by Streptomyces results from a decrease in the pool of GTP (or GDP), whereas antibiotic synthesis results from a different signal(s).

Acta Pathol Jpn, 1986 Feb, 36(2), 309 - 16
Pseudomembranous colitis in a patient of paraquat intoxication; Imamura T et al.; A 49 year-old man drank paraquat 7-8 fold of human fatal dose, and died of severe respiratory failure in 24 days in spite of intensive therapy . The autopsy revealed diffuse pulmonary fibrosis caused by prolonged intoxication of paraquat . An interesting finding was many raised plaques from 1 mm to 10 mm in diameter, observed in whole colon . Histologically, these plaques were composed of necrotic mucosa ("pseudomembrane"), disrupted crypts and edematous submucosa with fibrin education, intervening in normal colon tissue with sharp margins, and diagnosed as non-antibiotic-induced pseudomembranous colitis . Since the edematous submucosa of the raised plaque had a stratified fibrin education around a dilated capillary, it was speculated that the vessel injury by paraquat might play a role in the pathogenesis of pseudomembranous colitis.

Vestn Khir Im I I Grek, 1986 Feb, 136(2), 13 - 7
{Diagnosis and treatment of acute limited gangrene of the lung}; Neimark II; Based on an analysis of 49 patients with acute limited gangrene of the lung the author considers the main method of treatment of this disease to be a complex conservative treatment including the antibiotic therapy, sanitation of the gangrenous cavity and bronchial tree trachea, drainage of the abscesses, correction of immune disorders of the organism and normalization of the functioning of its important systems . The operative treatment is thought to be necessary in cases with severe complications such as bleedings, pyopneumothorax, septicopyemia . Operations under these conditions give high lethality rate and are followed by severe complications.

Antimicrob Agents Chemother, 1986 Feb, 29(2), 309 - 14
Cloning and molecular epidemiology of plasmid-determined fosfomycin resistance; Villar CJ et al.; The plasmid determinant of resistance to fosfomycin (For) was cloned into pBR322 and located in a 0.7-kilobase segment of DNA by transposon mutagenesis and in vitro deletion analysis . It encodes an 18-kilodalton protein located in the cytoplasm of resistant cells . Its synthesis is constitutive . The For genetic determinant is common to all plasmids isolated since 1975 in an hospital environment as determined by DNA-DNA hybridization . However, plasmids which carry For can be divided into two groups on the basis of size, pattern of antibiotic resistances, incompatibility specificity, and restriction and hybridization properties.

J Urol, 1986 Feb, 135(2), 343 - 5
Acute lobular nephronia; Wegenke JD et al.; Acute lobular nephronia is an unusual form of localized renal infection, which has a characteristic computerized tomographic and ultrasonographic appearance, and should be distinguished from abscess or other renal masses . Treatment is nonoperative, consisting of intensive antibiotic therapy.

Dis Colon Rectum, 1986 Feb, 29(2), 140 - 3
Cefazolin-induced pseudomembranous colitis resulting in perforation of the sigmoid colon; Osler T et al.; The seventh case of probable cefazolin-induced pseudomembranous colitis is reported . Perforation of the colon necessitated sigmoid resection . The postoperative course was protracted, and illustrates the difficulty of managing advanced pseudomembranous colitis when the oral route of antibiotic administration is not available . Although rare, pseudomembranous colitis related to cefazolin administration is a potentially fatal complication . The routine use of prophylactic antibiotics must be weighed against this possibility.

Ann Plast Surg, 1986 Feb, 16(2), 106 - 10
Salvage of the exposed breast implant; Weber J Jr et al.; Exposure of silicone breast implants may occur as a result of hematoma and infection, inadequate soft tissue coverage, use of steroids, or trauma . In various series the incidence of severe complications is reported to range from 1% to 4% . When exposure of the implant has occurred, most authors recommend removal with replacement four to six months later . In 11 patients we successfully salvaged the exposed breast implant . The technique was initially presented in 5 patients in 1974 . Successful salvage of the exposed implant involved (1) wound cultures with preoperative and postoperative antibiotic therapy, (2) excisional debridement of the skin wound, (3) open capsulotomy to relieve tension, (4) wound irrigation with neomycin-polymyxin or povidone-iodine, (5) closed catheter drainage, and (6) replacement with a sterile prosthesis . Secondary closure of these wounds was successful in all of the patients . Of the 11 patients, 9 were seen at two years postoperatively with results comparable in appearance and softness to the opposite breast . One of the patients required subsequent bilateral capsulotomies for firmness . The use of this technique is recommended for selected patients in whom there are no systemic problems related to wound healing and in whom sufficient soft tissue coverage is possible.

J Gen Microbiol, 1986 Feb, 132 ( Pt 2), 393 - 402
Microcin B17 blocks DNA replication and induces the SOS system in Escherichia coli; Herrero M et al.; Microcin B17 is a novel peptide antibiotic of low Mr (about 4000) produced by Escherichia coli strains carrying plasmid pMccB17 . The action of this microcin in sensitive cells is essentially irreversible, follows single-hit kinetics, and leads to an abrupt arrest of DNA replication and, consequently, to the induction of the SOS response . RecA- and RecBC- strains are hypersensitive to microcin B17 . Strains producing a non-cleavable SOS repressor (lexAl mutant) are also more sensitive than wild-type, whereas strains carrying a mutation which causes constitutive expression of the SOS response (spr-55) are less sensitive to microcin . Microcin B17 does not induce the SOS response in cells which do not have an active replication fork . The results suggest that the mode of action of this microcin is different from all other well-characterized microcins and colicins, and from other antibiotics which inhibit DNA replication.

Am J Kidney Dis, 1986 Feb, 7(2), 135 - 40
Pancreatitis: an important cause of abdominal symptoms in patients on peritoneal dialysis; Caruana RJ et al.; In an eight-month period, four patients in our peritoneal dialysis program developed acute pancreatitis, an incidence significantly higher than that in our hemodialysis program . Diagnosis was difficult since the symptoms of pancreatitis were similar to those of peritoneal dialysis-associated peritonitis . Further difficulties in diagnosis were due to unreliability of serum amylase levels and "routine" ultrasound examinations in suggesting the presence of pancreatitis . Computerized tomography performed in three patients showed enlarged, edematous pancreata with large extrapancreatic fluid collections in all cases . Two patients died, one directly due to complications of pancreatitis . One patient was changed to hemodialysis and showed clinical and radiologic resolution of his pancreatitis . One patient remains on peritoneal dialysis but has now had four attacks of acute pancreatitis . No patient had classic risk factors for development of pancreatitis . Review of patient histories showed no common historical factors except for renal failure itself, peritoneal dialysis, peritonitis, catheter surgery, and hypoproteinemia . It is possible that metabolic abnormalities related to absorption of glucose and buffer from dialysate or absorption of a toxic substance present in dialysate, bags, or tubing can cause pancreatitis in patients on peritoneal dialysis . We feel that a diagnosis of pancreatitis should be considered when peritoneal dialysis patients present with abdominal pain, particularly if peritoneal fluid cultures are negative or if patients with positive cultures do not have prompt resolution of symptoms with appropriate antibiotic therapy.

J Biol Chem, 1986 Jan 25, 261(3), 1230 - 40
Sequence-dependent recognition of DNA duplexes . Netropsin complexation to the AATT site of the d(G-G-A-A-T-T-C-C) duplex in aqueous solution; Patel DJ et al.; We have investigated intermolecular interactions and conformational features of the netropsin X d(G-G-A-A-T-T-C-C) complex by one- and two-dimensional NMR studies in aqueous solution . Netropsin removes the 2-fold symmetry of the d(G-G-A-A-T-T-C-C) duplex at the AATT binding site and to a lesser extent at adjacent dG X dC base pairs resulting in doubling of resonances for specific positions in the spectrum of the complex at 25 degrees C . We have assigned the amide, pyrrole, and CH2 protons of netropsin, and the base and sugar H1' protons of the nucleic acid from an analysis of the nuclear Overhauser effect (NOESY) and correlated (COSY) spectra of the complex at 25 degrees C . We observe intermolecular nuclear Overhauser effects (NOE) between all three amide and both pyrrole protons on the concave face of the antibiotic and the minor groove adenosine H2 proton of the two central A4 X T5 base pairs of the d(G1-G2-A3-A4-T5-T6-C7-C8) duplex . Weaker intermolecular NOEs are also observed between the pyrrole concave face protons and the sugar H1' protons of residues T5 and T6 in the AATT minor groove of the duplex . We also detect intermolecular NOEs between the guanidino CH2 protons at one end of netropsin and adenosine H2 proton of the two flanking A3 X T6 base pairs of the octanucleotide duplex . These studies establish a set of intermolecular contacts between the concave face of the antibiotic and the minor groove AATT segment of the d(G-G-A-A-T-T-C-C) duplex in solution . The magnitude of the NOEs require that there be no intervening water molecules sandwiched between the antibiotic and the DNA so that release of the minor groove spine of hydration is a prerequisite for netropsin complex formation.

Biochemistry, 1986 Jan 14, 25(1), 177 - 81
Evidence for nystatin micelles in L-cell membranes from fluorescence photobleaching measurements of diffusion; O'Neill LJ et al.; Diffusion of a nitrobenzoxadiazole derivative of the polyene antibiotic nystatin in the membranes of L cells is found to depend on the concentration of nystatin in the membrane . Its diffusion coefficient measured by fluorescence photobleaching decreases hyperbolically as the concentration of nystatin is increased . This behavior is reproduced when the concentration of the derivative is increased . In contrast, diffusion of a nitrobenzoxadiazole derivative of a phospholipid is insensitive to the nystatin concentration under these conditions . The nystatin-specific diffusion changes can be understood if nystatin exists in a monomer-micelle equilibrium within the membrane but cannot be accounted for by binding or phase partitioning.

Biochem Biophys Res Commun, 1986 Jan 14, 134(1), 338 - 43
Transcription but not translation is required for EDTA-induced autolysis in Escherichia coli; Prasad KS et al.; Rifampicin, but not chloramphenicol or other inhibitors of translation, inhibited EDTA-induced autolysis in Escherichia coli . Inhibition of EDTA-induced autolysis in E . coli was also observed with nalidixic acid and novobiocin, inhibitors of topoisomerase II . Rifampicin or nalidixic acid-resistant mutants of E . coli were resistant to the inhibitory effect of the respective antibiotic on EDTA-induced autolysis . The implications of these studies in regard to our understanding of the regulation of autolysis in E . coli are discussed.

Drug Nutr Interact, 1986, 4(3), 299 - 307
Effect of cephalexin and tetracycline on galactose absorption in rat small intestine; Barcina Y et al.; The effects of cephalexin and tetracycline HCl on D-galactose absorption in rat small intestine were investigated . Both antibiotics inhibited D-galactose uptake into isolated intestinal mucosa in a dose-dependent fashion . In vivo studies showed that cephalexin and tetracycline HCl reduced D-galactose absorption and that the transport defect was not reversible on cessation of antibiotic perfusion . Both the active and passive components of D-glactose absorption were inhibited by the antibiotics tested . Furthermore, both drugs reduced mucosa O2 consumption and inhibited D-galactose absorption when they were perfused in a contiguous loop . We conclude that the diminished D-galactose transport by rat small intestine after tissue exposure to either cephalexin or tetracycline HCl appears to be in part due to an insufficient energy supply.

Acta Chir Scand, 1986 Jan, 152, 19 - 21
Pharmacokinetics of dicloxacillin in serum and aortic wall during aneurysmal surgery; Almgren B et al.; Twenty-one patients undergoing elective surgery for abdominal aortic aneurysm were randomly assigned to receive 2 grams of dicloxacillin as an intravenous infusion either at the induction of anaesthesia, 3 hours or approximately 6 hours before surgery . Samples from serum and aortic tissue were simultaneously obtained so that antibiotic levels could be compared as a function of time . High concentrations of dicloxacillin in serum and aortic tissue were present already shortly after infusion and active levels were maintained in aortic tissue for approximately six hours . The kinetics of dicloxacillin was similar in serum and aortic tissue . These results support the need for antibiotic administration shortly before surgery to ensure adequate tissue levels of antibiotics.

Sex Transm Dis, 1986 Jan-Mar, 13(1), 40 - 4
The effect of tetracycline treatment on chlamydial salpingitis and subsequent fertility in the mouse; Swenson CE et al.; The effect of tetracycline X HCl, administered for 14 days starting before or after intraovarian bursa inoculation of the mouse pneumonitis biovar of Chlamydia trachomatis, was examined in mice . Mice that received no antibiotic developed acute salpingitis and subsequent hydrosalpinx . Only one of ten mated mice at 42-51 days after inoculation showed a normal, bilateral pregnancy . Initiation of tetracycline treatment two days prior to inoculation completely prevented the pathology associated with tubal chlamydial infection and fertility was as high (eight of ten) as in mice inoculated with sterile tissue culture supernate (eight of 11) . Initiation of treatment one week after inoculation prevented permanent tubal damage (two of 20 vs . 12 of 20; P = .001) and infertility (bilateral pregnancies, six of ten vs . one of ten; P = .027) in some, but not all, infected mice . Therapy began two weeks after inoculation resulted in a marginal improvement in the frequency of apparently normal oviducts (16 of 24 vs . eight of 20; P = .053) but not in fertility (bilateral pregnancies, four of 12 vs . one of ten; P = 0.19) . This model may be of value in studies of the treatment of upper genital tract infection with C . trachomatis.

J Am Acad Dermatol, 1986 Jan, 14(1), 94 - 100
Cutaneous draining sinus tract: an odontogenic etiology; Cioffi GA et al.; Although the most common cause of the intermittently suppurating cutaneous sinus tract in the face and neck area is chronic dental infection, chronic draining sinus tracts of the face and neck continue to be a diagnostic challenge . The attending clinician must look carefully for a potential odontogenic infection; chronicity, lasting for weeks, months, and even years and the recognition of the lesion as a sinus tract are keys to making the correct diagnosis . Diagnostic errors can result in multiple surgical excisions and biopsies, long-term antibiotic therapy, and even radiation therapy or electrodesiccation . A review of 137 cases of cutaneous draining sinus tracts from the literature is presented, and four cases are reported . Conservative, nonsurgical root canal therapy is recommended as the first choice of treatment.

Antibiot Med Biotekhnol, 1986 Jan, 31(1), 3 - 7
{Valinomycin biosynthesis and the dynamics of the content of macroergic phosphorus compounds in Streptomyces cyaneofuscatus}; Telesnina GN et al.; The pattern of accumulation and consumption of macroergic phosphoric compounds such as polyphosphates, pyrophosphate and ATP in the mycelium of the valinomycin-producing organism was studied . The content of high polymeric polyphosphates in the high productive strain A of S . cyaneofuscatus was much lower than that in the isogenic low productive strain B, which was indicative of their participation in providing bioenergetics of antibiotic production . Cultivation of the low productive strain B in the presence or absence of the A-factor showed that the mutant reduced its sporulation and provided a 40-fold increase in biosynthesis of valinomycin . However, no difference in consumption of diverse polyphosphate fractions was observed.

Antibiot Med Biotekhnol, 1986 Jan, 31(1), 13 - 6
{Azo derivatives of levorin}; Mitrofanov AA et al.; Levorin, an aromatic heptaenic antibiotic and sodium nitrite in solution of acetic acid formed a diazo compound . In the diazo reaction this compound interacted with beta-napthol or H-acid . The resulting azo compounds were readily soluble in organic solvents . In water their nitrites formed true solutions . The biological activity of the azo levorins was 100-200 times lower than that of the initial levorin . The physico-chemical characteristics of the azo levorins are presented.

Am Heart J, 1986 Jan, 111(1), 128 - 35
Right-sided valvular endocarditis: etiology, diagnosis, and an approach to therapy; Robbins MJ et al.; Right- and left-sided endocarditis are two distinct entities, both clinically and experimentally . As such, they require different clinical approaches . The accurate diagnosis of right-sided endocarditis rests largely on a high index of suspicion which is often raised in the case of an intravenous drug abuser with fever, especially when pulmonary infiltrates are detected . Two-dimensional echocardiography can be expected to confirm the diagnosis in approximately 80% of the cases . Measurement of the echocardiographically visualized vegetation provides both prognostic and therapeutic information . When the vegetation is less than 1.0 cm in diameter, antibiotic therapy can be reasonably expected to cure the infection . Despite a prolonged fever, we recommend continued medical management in these cases, as lack of response to medical management is almost exclusively seen in cases in which echocardiographically determined vegetation size is greater than or equal to 1.0 cm, perhaps because of the slower metabolic rate of bacterial colonies within these large vegetations . If, however, after 3 weeks of antibiotic therapy, fevers persist in a patient in whom two-dimensional echocardiography reveals a vegetation of greater than or equal to 1.0 cm, surgical intervention should be contemplated . Prior to such intervention, the physician must be careful to exclude other sources of fever, such as abscesses, phlebitis, and drug reactions, as indicated in Table III . Also, adequate antibiotic levels should be documented prior to surgical intervention . Because of the adverse effect on vegetation size upon the response to antibiotics, there may be a role for anticoagulation in order to potentiate the effects of the antibiotic therapy; however, this is purely speculative at present.(ABSTRACT TRUNCATED AT 250 WORDS)

Strahlenther Onkol, 1986 Jan, 162(1), 25 - 30
{Total lymphoid irradiation in chronic polyarthritis--a new therapeutic concept}; Herbst M et al.; Eleven patients with refractory rheumatoid arthritis were submitted to a total lymphoid irradiation up to a dose of 20 Gy . A constant improvement of clinical symptoms was observed in four out of the eleven patients already during the treatment and in the other patients not later than two months after . The frequency of attacks decreased and the number of joints involved in the attack was reduced . Morning rigidity and joint swellings decreased . One patient developed joint empyemas 4 and 26 months after the treatment . Four patients died in the meantime . In two patients the cause of death were renal insufficiency and a postoperative cardiogenic shock associated with generalized amyloidosis . The third patient died because of a toxically induced left cardiac decompensation with sepsis that could not be controlled by antibiotic drugs and multiple joint empyemas . The fourth patient developed an abscess after surgical treatment of a Kaposi syndrome . She died three months later from acute left cardiac decompensation . The therapy induced a lymphocytopenia with decrease of T helper lymphocytes and unchanged number of T suppressor lymphocytes . The constant therapy results of total lymphoid irradiation in primary chronic polyarthritis is probably due to this modification in the immune regulation.

Gastrointest Radiol, 1986, 11(1), 85 - 9
Percutaneous biliary drainage in acute suppurative cholangitis; Nunez D Jr et al.; One hundred and sixteen percutaneous drainage procedures of the biliary system were performed in a 2-year period . Eight of 9 acutely ill patients with the diagnosis of acute suppurative cholangitis were successfully treated nonoperatively . They represented 26% of all patients with benign or postsurgical obstruction referred for biliary decompression . Conversely, acute suppurative cholangitis only occurred in 2.3% of patients with underlying malignant disease . These observations are considered most relevant in predicting the purulent nature of the disease, with further implications for patient management . Early recognition and prompt decompression of the biliary system are mandatory, along with the appropriate antibiotic coverage . Our experience compares favorably with surgical results and the procedure is proposed as the method of choice for the initial treatment of acute suppurative cholangitis.

Am J Perinatol, 1986 Jan, 3(1), 58 - 60
Necrotizing fasciitis of the scalp in neonates; Gibboney W et al.; Two premature infants with acute necrotizing fasciitis of the scalp are reported . In both cases the infection most likely arose from infiltrations of intravenous fluids into the subcutaneous region of the scalp . Aggressive surgical debridement, as well as antibiotic therapy, resulted in healing in both infants . A review of neonatal fasciitis is included.

Plast Reconstr Surg, 1986 Jan, 77(1), 50 - 9
Costochondritis: pathogenesis, diagnosis, and management considerations; Chicarilli ZN et al.; The management of costochondritis of the chest wall is reviewed and four illustrative cases presented . Adequate debridement is the single most important factor to ensure eradication of this disease . Well-vascularized tissue coverage reduces ischemic factors, resists secondary infection by contamination, and promotes rapid healing . The pectoralis major, latissimus dorsi, and rectus abdominis muscle flaps are the primary choices for pedicle-flap coverage . Antibiotic coverage was not extended beyond 3 weeks in these cases, and no recurrences have been noted over a 1- to 3-year follow-up.

J Thorac Cardiovasc Surg, 1986 Jan, 91(1), 99 - 105
Retrohepatic cavoatrial bypass for coarctation of inferior vena cava with a polytetrafluoroethylene graft; Victor S et al.; Eight patients with chronic Budd-Chiari syndrome resulting from coarctation of the inferior vena cava underwent operation . Transatrial dilatation was of no avail in the first case . The obstructed segment was directly visualized in the subsequent seven cases by a transthoracic, transdiaphragmatic, retroperitoneal approach . In these latter seven cases, severe hourglass constriction of the inferior vena cava was observed just above the right hepatic vein . There was no evidence of inflammation, extrinsic compression, or thrombosis . Retrohepatic cavoatrial bypass with an antibiotic-sterilized aortic homograft was unsuccessful in three patients . Five patients including one with homograft failure underwent successful retrohepatic cavoatrial bypass with a polytetrafluoroethylene graft (20 mm plain in four cases and 16 mm ringed graft in one case) . These patients have been followed up for 21 months to 6 years with no recurrence of symptoms . The term coarctation of the inferior vena cava appears more appropriate than membranous obstruction of the inferior vena cava because of the operative findings in the present series.

J Bone Joint Surg Am, 1986 Jan, 68(1), 103 - 12
Sternocostoclavicular hyperostosis . A report of nineteen cases, with special reference to etiology and treatment; Chigira M et al.; The cases of nineteen patients with sternocostoclavicular hyperostosis were reviewed retrospectively . Of particular interest were the responses to antibiotics and prostaglandin inhibitors . The prostaglandin inhibitors relieved the pain within three to four weeks in sixteen of eighteen patients so treated . However, the inhibitors gradually became less effective in most patients . Oral antibiotics were more effective than the inhibitors in relieving the pain of eight of the eleven patients who were given antibiotics . Pustulosis palmaris and plantaris, commonly associated with sternocostoclavicular hyperostosis, diminished after antibiotic therapy, as did the chest pain in most patients . The similarities between the age and sex distributions 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 be a so-called bacterid reaction and the hyperostosis, a manifestation of a systemic reaction to a focal infection.

J Bacteriol, 1986 Jan, 165(1), 47 - 52
Genetic and physical characterization of IncM plasmid pBWH1 and its variance among natural isolates; Hopkins JD et al.; We present a genetic and physical characterization of the IncM plasmid pBWH1 . A physical map was constructed for the enzymes EcoRI, BamHI, SalI, BglII, HindIII, MstII, and XhoI . A series of deletions and a series of subclones of pBWH1 were constructed and used to determine the locations on this map of the transfer region; the replication region; and the genes determining resistance to beta-lactams, chloramphenicol, the sulfonamides, and gentamicin . We compared 51 different isolates, including isolates which had lost individual antibiotic resistances or the transfer phenotype, and showed that variations occurred in all regions of the plasmid genome . Frequently, correlations could be made between phenotypic variation and variation of the EcoRI fragments which contained the gene determining that phenotype.

Drugs Exp Clin Res, 1986, 12(11), 895 - 7
Penetration of piperacillin into renal cysts; Bonadio M et al.; Concentrations of piperacillin in the cystic fluid of eight patients with simple renal cysts were assessed after each patient had been given single or multiple doses of the antibiotic . Concentrations ranged from non-detectable to 9 mcg/ml.

Clin Ther, 1986, 9(1), 77 - 83
Comparison of cefoxitin and clindamycin-gentamicin for pelvic infections; Larsen JW Jr et al.; Cefoxitin and clindamycin-gentamicin were compared in a randomized study of antibiotic therapy for infections of the pelvis in 91 women . Clinical diagnoses included pelvic inflammatory disease (53), endomyometritis after cesarean section (24), and cellulitis following gynecological surgery (14) . Treatment failures occurred in four (10%) of the 41 patients treated with cefoxitin compared with eight (16%) of the 50 patients treated with the clindamycin-gentamicin combination . Single-drug therapy with cefoxitin was shown to be as effective as the combination of clindamycin and gentamicin.

Ann Med Interne (Paris), 1986, 137(5), 372 - 4
{Cardiac manifestations of Lyme disease}; Allal J et al.; Three cases of Lyme's disease with cardiac involvement are reported . One patient had myocarditis complicated by symptomatic complete AV block and two patients had asymptomatic 1st degree AV block . There were no abnormalities on echocardiography . The cardiac changes occurred between the 18th and 40th day after the onset of the disease and persisted 10 days: however these conduction defects may vary within a few hours . A rapid and complete cure was obtained with antibiotic therapy.

Vet Med Nauki, 1986, 23(10), 76 - 82
{Comparative pharmacokinetic research on amoxicillin in agricultural animals}; Lashev L; Described is the pharmacokinetic of amoxycillin following i/v and oral administration to calves, pigs, and rabbits at the rate of 10 mg per kg of body mass and to turkeys at 30 mg/kg body mass . The pharmacokinetic was found to be of first order, whereas a bispatial model was applicable after i/v introduction of the sodium salt and a monospatial model--following the oral administration of amoxycillin trihydrate . Discussed are the differences in the absorption, distribution, and excretion of the antibiotic as affected by the mode of application and the species peculiarities of the animals.

Scand J Thorac Cardiovasc Surg, 1986, 20(3), 203 - 7
Mediastinal infection following open-heart surgery . Treatment with retrosternal irrigation; Verkkala K et al.; A consecutive series of 1083 patients undergoing open-heart surgery was prospectively observed for infectious complications . Postoperative mediastinitis developed in 15 cases (1.4%) . Surgical management of the mediastinal complication consisted of careful debridement of the sternal wound and the anterior mediastinum, followed by continuous retrosternal irrigation with an antiseptic or antibiotic solution after sternal refixation . The mean duration of mediastinal irrigation was 12.7 days . This treatment was successful in 13 of the 15 patients . In 2 of the 13, however, secondary refixation became necessary to stabilize the fragmented sternum . Repeated refixation with mediastinal irrigation was effective in one of these patients . The other underwent removal of the fragmented sternum followed by muscle plasty, but died unexpectedly of aortic dissection when signs of infection were subsiding . Two patients (13%) treated with closed chest irrigation died of recalcitrant mediastinal infection.

Rev Pneumol Clin, 1986, 42(5), 226 - 30
{Transparietal pulmonary puncture in the diagnosis of excavated pulmonary masses . Apropos of 18 cases}; Le Chevalier B et al.; The aetiological diagnosis of excavated pulmonary opacities is sometimes uneasy, hovering between squamous cell carcinoma and abscess . Normal results at bronchoscopy and two weeks of antibiotic therapy do not always provide a definite answer . The authors report 18 cases of such excavated masses and conclude that transparietal needle aspiration can establish the diagnosis provided some technical procedures are followed and the samples obtained are examined by skilled cytologists.

Drugs, 1986, 32 Suppl 3, 17 - 20
Penetration and concentration of cefadroxil in sputum, lung and pleural fluid; Nightingale CH; The penetrability of cefadroxil in sputum, pleural fluid and lung tissue was examined in patients with acute respiratory infections, or who were undergoing thoracic surgery . The concentration of antibiotic in these tissues after single doses of 500 mg or 1 g was approximately half of that seen in serum, but persisted longer . In all biological matter studied, the concentration of cefadroxil was sufficient to inhibit pathogens such as S . aureus, S . pneumoniae and S . pyogenes, shown to be common causes of respiratory illnesses . Thus, cefadroxil should be a useful agent in the treatment of such infections.

Bull Soc Pathol Exot Filiales, 1986, 79(4), 557 - 70
{Illicit sales of drugs in Senegal . Consequences for community health}; Fassin D; The relatively recent development of parallel drug markets in the Third World has not yet been specifically studied . A research on illicit drug sale was carried out in Pikine, a 600,000 people suburb of Dakar: all items provided by all sellers observed on the markets of the town were inventoried; their indications and posologies were given by a sample of 20 among the 100 identified sellers; complementary information was obtained from the official structures of drug distribution . The list of all medications available shows 23 items--12 directed at {symptoms}, and 11 at {causes} . The indications and posologies are remarkably similar for the 20 sellers, whose training was done in well-structured channels outside the official network . Evaluation of the potential consequences of these parallel markets for community health shows: 1) a probably beneficial impact of some medications, such as analgesics, antimalarials, antibiotic eye ointment; 2) exposure to individual risks (tetracyclines, sulfamids) and collective risks (antibiotics, not widespread yet, but capable of selecting resistant germs) . Moreover, this illicit sale must be understood in its social context where buying drugs on the markets is the least expensive and most accessible solution for underprivileged people, because of scarcity of resources in the dispensaries . Thus, rather than to automatically condemn illicit drug sale, it seems more appropriate and urgent to evaluate the risks of medications available in each of the countries involved, to develop health information in the population, and meanwhile to make access to drugs in primary health care structures easier.

Vox Sang, 1986, 51(4), 321 - 3
An IgG, gentamicin sulfate-dependent antibody found during prenatal antibody screening; Peloquin PM et al.; The serum of a prenatal patient was found to contain an IgG antibody that reacted with all red cells suspended in solutions containing the antibiotic gentamicin sulfate . The antibody was nonreactive with red cells suspended in media containing chloramphenicol, neomycin, hydrocortisone or inosine . Since gentamicin sulfate is used in the suspending medium of some commercial reagent red cell products, difficulties in the interpretation of antibody detection and identification tests may arise when patient sera contain gentamicin-dependent antibodies.

J Urol (Paris), 1986, 92(6), 339 - 43
{Extracorporeal lithotripsy in the treatment of renal lithiasis . 5 years' experience}; Chaussy C et al.; The historical background to extracorporeal lithotripsy using shock waves is described and indications for use of this treatment discussed in relation to other types of therapy for reno-ureteral lithiasis: percutaneous or trans-ureteral endoscopy . The reduction in invasive surgical procedures is emphasized . The first human use of extracorporeal lithotripsy by shock waves dates back to 1980 . Since then, more than 30,000 calculi have been treated in this way, either exclusively or in combination with other therapy . For simple small calculi (less than 1 cm in diameter and situated in the pelvis or a calyx) the incidence of complications is minimal: renal colic (15%), fever (13%), need for complementary therapy (7%) . With extension of use of extracorporeal lithotripsy to complex calculi (multiple calculi, staghorn calculi) these figures increased to 30, 5 and 12% respectively . Patients with obstructive and infected lithiasis were treated by percutaneous drainage nephrostomy with intensive antibiotic therapy prior to extracorporeal treatment . Extending indications also provided data on contraindications: coagulation disorders, major vascular problems, abnormal size or weight of patient, pregnancy and finally difficulty in localizing calculi . Of interest is the almost total lack of efficacy of shock waves for treating staghorn calculi . Treatment in these cases should be by an initial percutaneous approach to reduce size of calculus followed by extracorporeal lithotripsy under nephrostomy cover . Surgery for lithiasis should therefore be reserved for complex lithiasis cases with large caliceal calculi proximal to a long narrow infundibulum and to calculi proximal to a stenosis of pyelo-ureteral junction . Whenever possible, lumbar ureter calculi should be raised towards the pelvis by endoscopic manipulation before extracorporeal lithotripsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Intensive Care Med, 1986, 12(6), 407 - 11
Acute epiglottitis: management by short duration of intubation and hospitalisation; Gerber AC et al.; One hundred and thirty-seven patients with acute epiglottitis were studied retrospectively with regard to the efficacy and safety of short duration of intubation and hospitalisation . All patients were treated by nasotracheal intubation and antibiotic therapy . Inhalation anesthesia with halothane/oxygen was the preferred method for intubation (80.3%) . Extubation was based on clinical improvement in 88.1% and on laryngoscopy in 11.9% of cases . Fifty-four percent of the patients were extubated successfully within 24 h and 94.8% within 48 h . Three patients (2.2%) had to be reintubated once . The mean duration of intubation was 27.6 h (range 8-86) and of hospitalisation 4.0 days (range 2-9) . Two children (1.5%) died because of severe hypoxic brain damage due to cardiorespiratory arrest prior to hospital admission . A follow-up study conducted via the family physician revealed only two major complications (granulation polyp of the vocal cords, 1; long-lasting hoarseness, 1) . It is concluded that short duration of intubation and hospitalisation are effective and safe in the management of acute epiglottitis.

Int J Immunopharmacol, 1986, 8(6), 657 - 64
Acetylspiramycin and the immune system--II . Effects on lymphocyte proliferation, lymphokine production, delayed-type hypersensitivity and antibody production; Li SY et al.; The effects of the antibiotic acetylspiramycin (ASPM) on lymphocyte function were studied in vitro and in vivo . When added to lymphocyte cultures in vitro, ASPM inhibited splenic lymphocyte transformation induced by phytohemagglutinin (PHA), lipopolysaccharide (LPS) and antigen . It also depressed production by spleen cells of the lymphokine inducing procoagulant activity in mouse macrophages . Spleen cells from mice given ASPM orally showed enhanced responses to PHA, but normal responses to LPS . The capacity to produce lymphokine was increased early after oral ASPM and slightly decreased after prolonged administration . Oral ASPM had no effect on the production of antibodies and a very slight enhancing effect on the development of delayed-type hypersensitivity to sheep red blood cells.

Arch Immunol Ther Exp (Warsz), 1986, 34(2), 203 - 8
Lymphatic system of mice born from mothers treated with ampicillin or cloxacillin during gestation; Skopinska-Rozewska E et al.; Ampicillin, an antibiotic, widely used for combating bacterial infections exerts great influence on cells of the immune system of mouse and man . We have studied the effect of ampicillin and cloxacillin treatment of mice in the final week of pregnancy on the development of the lymphatic system of their offsprings . The mice born from antibiotic or saline treated mothers were examined 30 days after delivery . The examination of relative organ weight, cellularity and histopathological picture of lymphatic system (thymus, spleen and lymph nodes) and some other organs was performed . In the group of mice from ampicillin treated mothers we have found decreased relative weight of thymus and spleen and increased weight of lymph nodes with increased cellularity in thymus and lymph nodes . In the group of mice from cloxacillin treated mothers increased cellularity of thymus and lymph nodes was found . The histopathological study of lymphatic organs structure did not reveal any specific changes but the symptoms of focal degeneration and fat necrosis were found in livers of mice born from ampicillin treated mothers . Moreover, in mice born from antibiotic treated mothers the significant lymphocytosis in the peripheral blood was assessed . It was accompanied by an increase of granulocyte number in offsprings from ampicillin treated mothers and increase of monocyte number in those of cloxacillin treated . In conclusion, it could be suggested that ampicillin treatment during pregnancy would exert some effect on the development of lymphopoietic system of fetuses.

Acta Paediatr Hung, 1986, 27(3), 267 - 73
Cytogenetic studies on peripheral blood cultures of neonates treated in an intensive unit; Dobos M et al.; The possible causes of an increased rate of structural chromosomal aberrations and sister chromatid exchange in peripheral blood cultures of mechanically ventilated newborns in an intensive care unit were investigated . No cytogenetic abnormalities were found in low-birth-weight babies affected by hypoxia and acidosis during their first week of life . The rate of chromosome breakage and sister chromatid exchange was increased in blood cultures of neonates continuously ventilated with 70-80 vol% oxygen for a long period of time . The incidence and degree of chromosomal damage, although showing wide individual variations, was related to the duration of oxygen treatment . In addition to high oxygen tension, other environmental factors of intensive care therapy like antibiotic and chemotherapeutic agents may be responsible for the mutagenic effect . The results indicate once again the importance of continuous pO2-monitoring of ventilated newborns.

Antibiot Med Biotekhnol, 1986 Jan, 31(1), 52 - 5
{Clinico-biochemical aspects of the polychemotherapy of disseminated lymphogranulomatosis resistant to the COPP protocol}; Breivis PV et al.; With a purpose of providing efficient treatment of extended lymphogranulomatosis resistant to the routine COPP program, new programs of polychemotherapy including the use of an antibiotic, plant alkaloid, alkylating agent and glucocorticoid were developed and studied . The optimal rhythm and regimen of the drug administration were developed . The study was based on the treatment of 65 patients . The clinical trials showed that the ALVP program including the use of adriablastin, lofenal, vinblastin and prednisolone was the most efficient . Its use provided a significant therapeutic effect in 77 per cent of the patients . The BrLVP program including the use of bruneomycin, lofenal, vinblastin and prednisolone, the RLVP program including the use of rubomycin, lofenal, vinblastin and prednisolone, the DLVP program including the use of dactinomycin, lofenal, vinblastin and prednisolone and the BlLVP program including the use of bleomycin, lofenal, vinblastin and prednisolone were less efficient and provided the therapeutic effect in 66, 63, 60 and 60 per cent of the patients respectively . The direction of shifts in the spectrum of the blood serum enzymes mainly corresponded to the results of clinical trials . This first of all referred to the ALVP and BrLVP programs . The use of these programs provided normalization of the hexokinase and lactate dehydrogenase activity of the serum and positive shifts in the isoenzyme spectrum.

Drugs Exp Clin Res, 1986, 12(6-7), 627 - 33
Structural features determining the haemolytic activity of vacidin A derivatives; Mazerski J et al.; The haemolytic activity of aromatic heptaene antifungal antibiotics (vacidin A and its analogues) can be decreased by chemical modification . It has been shown that the ionic state of the polar head of the antibiotic molecule is essential for this activity . The effect of the net charge of the antibiotic molecule on association constant, K, between polyene and membrane-located cholesterol; and the number, n, of antibiotic molecules per one erythrocyte critical for lysis induction was investigated . In addition, changes in the structure of the polyene-cholesterol complex were monitored by circular dichroism spectroscopy . Zwitterionic native antibiotics (vacidin A and gedamycin), the negatively charged N'-acetyl derivatives and the positively charged methyl esters were used in these studies . The results presented indicate that two different phenomena are responsible for the decrease in the haemolytic activity of the compounds studied: for N'-acetyl derivatives the decrease of activity is mainly a result of lower affinity of negatively charged molecules to the membranes; for methyl esters the drastic decrease of activity is mainly a result of the different structure of the antibiotic-cholesterol complex . The permeabilizing species formed from these complexes are characterized by very low efficiency of ion permeation.

Drugs Exp Clin Res, 1986, 12(6-7), 619 - 26
Interaction of lucensomycin with cholesterol in membranes: kinetic and structural studies; Capuozzo E et al.; The variations of optical density and fluorescence of lucensomycin are good indices of the binding of this polyenic antibiotic to membranes . The former parameter reflects more generally the binding to any site present in the membrane, while the latter is more specific for binding to cholesterol . Equilibrium titration experiments performed in the presence of an excess of membrane-bound cholesterol suggest that lucensomycin self-associates and that the binding and polymerization sites of the antibiotic are identical or quasi-identical; hence polymerization leads to a loss of binding sites and vice versa . The non-steroidal components of the membrane (such as proteins and lipids) seem to affect the rate of the individual reaction leading to the formation of the cholesterol-lucensomycin complexes, rather than the ratio among these heterologous aggregates at equilibrium . Polyene concentrations, which induce detectable proton release from unilamellar vesicles, are at least two orders of magnitude higher than those necessary to perform a spectroscopic titration of membrane cholesterol.

Cancer Chemother Pharmacol, 1986, 17(3), 241 - 6
Doxorubicin binds in a cooperative manner to myocardial cells . Two binding sites; Wassermann K et al.; Experimental evidence indicates that the anthracycline antibiotic doxorubicin (adriamycin) localizes mainly in cell nuclei of cardiac cells and has a high affinity to several cellular constituents in addition to DNA . In the present study the cellular kinetics of doxorubicin in cultured rat myocardial cells were determined by measuring its uptake, its binding pattern over a concentration range of 0.1 mM to 80 microM, and the cellular release by means of {14-14C}doxorubicin . The binding kinetics of doxorubicin were compared with the doxorubicin-induced inhibition of {methyl-3H}thymidine incorporation into DNA . It is demonstrated that at micromolar concentrations doxorubicin is readily taken up by myocardial cells and that myocardial cells have the ability to bind doxorubicin at two specific binding sites and that a noncooperative high-affinity/low-capacity type and a positive cooperative type of binding are involved, as indicated by the positive slope in the initial region of the binding isotherm (Scatchard plot) . A dose-dependent inhibition of {methyl-3H}thymidine incorporation into DNA is demonstrated . It is suggested that this is associated with the positive cooperative binding of doxorubicin . The cellular release of doxorubicin appeared to be biphasic, with estimated half-lives of about 5-6 h for the initial phase and 50-60 h for the terminal phase . The results of this study indicate that doxorubicin preferably binds to sites within myocardial cells and that the positive cooperative binding pattern is due to DNA as one of the binding sites . A relationship between the noncooperative high-affinity/low capacity binding and the pharmacological activity has yet to be determined.

Vopr Onkol, 1986, 32(7), 61 - 7
{Potentiation of the selective antitumoral effect of cyclophosphamide and 5-fluorouracil by its combination with amphotericin B and diacarb}; Iaremenko KV et al.; The paper deals with the results of experiments which were carried out on 10 tumor models and used approximately 1,000 animals (mice and rats of different strains) . Such cytostatic drugs as cyclophosphamide (alkylating agent) and 5-fluorouracil (antimetabolite) showed a significantly enhanced antitumor and metastation--preventing effect when used in combination with polyene antibiotic amphotericin B and a diuretic drug--diacarb . This was matched by a pronounced amelioration of toxic side effects and an increase in the animals' lifespan . The said method of treatment should be integrated with oncological practice.

Scan Electron Microsc, 1986, (Pt 1), 253 - 62
Quantitative renal vascular casting in nephrology research; Gattone VH 2nd et al.; The present paper describes the use of a quantitative renal vascular casting method to study the changes associated with kidney disease . Several animal models of hypertension (spontaneously hypertensive rat, SHR, with its normotensive rat the Wistar Kyoto, WKY; Dahl salt sensitive DS - hypertensive, and salt resistant DR - normotensive) were examined at time points when the systemic blood pressure was rising (6 and 12 weeks of age) and following renal denervation (in SHR-WKY rats) . The SHR appears to have a smaller caliber afferent arteriole at both 6 and 12 weeks of age . This difference is probably not entirely due to sympathetic vasoconstriction since the strain related afferent arteriolar diameter difference was still present after renal denervation . In the Dahl rats, there is not much of an intrarenal vascular difference between the DS and DR rats with the only real finding of a smaller distal afferent arteriolar diameter found in outer cortical nephrons of the DR . The two models of acute renal failure (ARF) that were studied include, the glycerol model (known to initially cause an intense vasoconstriction) and gentamicin, a nephrotoxic antibiotic . Two time points were examined for each of these models . As expected in the glycerol model there was an intense vasoconstriction at three hours which essentially was gone at 3 days - a time when the renal failure was fulminant . The glomerulus appeared to be contracted at three hours as well . In the gentamicin model no renal vascular alteration was seen at 6 days, when renal failure was mild while at 10 days, when renal failure was pronounced, outer cortical afferent arterioles appeared to be moderately constricted . In the 5/6 nephrectomy model of chronic renal failure, the glomeruli were smaller in rats in renal failure than in the controls.

Childs Nerv Syst, 1986, 2(2), 90 - 2
Brain abscess in children; Hegde AS et al.; During that last 6 years, 100 children have been treated for brain abscess at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore . Of these, 69 abscesses were otogenic . The treatment included aspiration of the abscess (84% of cases) and antibiotic therapy . CT scan as a diagnostic tool was available only for a few cases in the last year . In 16% of the cases the abscess was excised . The overall mortality was 21% . Of the surviving children, 76% recovered totally . Epilepsy as a sequel occurred in 21% of the cases . The fact that mortality continues to be high is attributed to the degree of impairment of consciousness of the children at the time of admission . Early detection and successful treatment of brain abscess in children still remain a clinical challenge.

Vet Med Nauki, 1986, 23(2), 65 - 70
{Pharmacokinetic research with poultry}; Lashev L; Tested was the pharmacokinetic property of amoxicillin following intravenous and oral application to chickens, turkeys, and pigeons . The dynamic of blood and tissue concentrations of the antibiotic were determined with pigeons following oral administration . Calculated were the pharmacokinetic parameters with regard to blood, kidneys, liver, lungs, and heart . The results obtained with chickens and turkeys were comparatively studied.

J Fr Ophtalmol, 1986, 9(1), 41 - 3
{Incidence of allergy to eyedrops . Results of a prospective survey in a hospital milieu}; Vadot E et al.; An estimation of the frequency of allergic contact reactions to eyedrops was obtained by means of a prospective study on hospitalized patients . The incidence of cases with a positive patch test was 6% during hospital care . The drugs blamed were atropine (allergic contact reaction in 3% of treated patients), phenylephrine (risk 2.6%) and neomycin (risk 1.7%) . The preservatives were not involved in any case . More than half of the patients had a previous history of eyedrop contact allergy, but they only rarely knew which drug was involved . The systematic use of patch tests to identify the allergenic drug(s), the accurate information of the patient and the parcimonious use of allergenic drugs, particularly of antibiotic eyedrops, are simple measures which should decrease notably the incidence of allergic contact reactions.

Z Parasitenkd, 1986, 72(3), 281 - 92
The surface membrane of Leishmania mexicana mexicana: comparison of amastigote and promastigote using freeze-fracture cytochemistry; Tetley L et al.; The freeze fracture replica technique has been used to compare the plasma membranes of amastigote and promastigote stages of Leishmania mexicana mexicana with respect to intramembranous particle (integral protein) distribution and to beta-hydroxysterols content as revealed by the distribution of lesions induced by the polyene antibiotic filipin . Intramembranous particle (IMP) density was greater in promastigote than in amastigote plasma membranes . Intramembranous particles were more abundant in the protoplasmic face (PF) than in the exoplasmic face (EF) of promastigotes, but this situation was found to be reversed in amastigotes . Filipin-induced lesions in glutaraldehyde-fixed parasites indicated higher levels of beta-hydroxysterols in the amastigote than in the promastigote plasma membrane, and in the promastigote flagellar membrane than in the body membrane . Amphotericin B (a related polyene antibiotic used in chemotherapy of leishmaniasis) induced IMP aggregation in the PF of unfixed amastigotes but did not appear to influence sterol distribution as demonstrated by freeze-fracture of subsequently-fixed and filipin-treated organisms.

Med Pediatr Oncol, 1986, 14(2), 81 - 5
Legionnaires' disease in patients with cancer; Nunnink JC et al.; A 4-year experience with Legionella pneumophila (LD) diagnosed in 36 patients with cancer was reviewed . Cancer patients represented 24% of the total population of patients acquiring LD during that time . Hematologic neoplasms (42%) and lung cancer (22%) accounted for the majority of afflicted patients . Nosocomial infections occurred in 42% of the patients evaluated . Several risk factors were assessed, and only neutropenia, and previous steroid therapy played a causal role (p less than .05) when assessed in a retrospective case control fashion . Overall mortality in oncology patients with LD (53%) was high and underscores the need rapidly to diagnose and treat this entity . This mortality decreased after 1977 when an effective antibiotic was utilized . Mixed infections also played a major role in outcome and occurred in 31% of the 36 patients studied . The mortality in these cancer patients was 73%, and this emphasizes the need to exclude and treat concomitant bacterial or fungal infections.

J Toxicol Environ Health, 1986, 18(2), 231 - 40
Influence of in vitro ubiquinone antagonists on doxorubicin toxicity in vivo; Tabora O et al.; Doxorubicin is an anthracycline antibiotic with a very wide spectrum of anticancer activity . It has a great potential for clinical cardiotoxicity, however . One mechanism suggested for the cardiotoxicity is inhibition of ubiquinone-dependent enzymes . It was our purpose to study this possible mechanism using ubiquinone antagonists as probes . The effect on doxorubicin toxicity of three in vitro ubiquinone antagonists was tested in mice . Two of the antagonists, 2-hydroxy-3-n-dodecylmercapto-1,4-naphthoquinone and 2,3-dimethoxy-5-beta-naphthylmercapto-1,4-benzoquinone, enhanced doxorubicin toxicity in vivo as measured by survival . The latter was significantly toxic to mice, by itself . This effect was completely blocked by ubiquinone pretreatment, but only reduced by tocopherol pretreatment . Neither ubiquinone nor tocopherol was able to decrease the toxic interaction between doxorubicin and either of the ubiquinone antagonists . Cardiac and hepatic glutathione reductase and glutathione peroxidase activities were measured in studies using the 2,3-dimethoxy-5-beta-naphthylmercapto-1,4-benzoquinone . This compound appeared to cause a slight reduction in the activity of hepatic glutathione reductase . It appears that these antagonists are not useful to probe the relationship between doxorubicin cardiotoxicity and ubiquinone enzyme inhibition.

Jpn J Antibiot, 1986 Jan, 39(1), 133 - 40
{Study of concentrations of clindamycin phosphate in bone marrow blood and tissue}; Nakamura N et al.; Clindamycin phosphate (CLDM) was administered to 33 surgical cases in orthopedics to treat or prevent infection (600 mg in 15 cases and 1,200 mg in 18 cases by intravenous drip infusion over 60 minutes) and the concentrations of CLDM in the bone marrow blood and tissue of the operative field as well as in venous blood were determined with the cup plate method of bioassay by collecting specimens immediately after completion of infusion or 30 or 60 minutes later . The concentration of CLDM in bone marrow blood averaged 104.3 approximately 105.5% of the corresponding concentration in venous blood in the cases receiving 600 mg and 101.3% in those receiving 1,200 mg . The concentration of CLDM in bone marrow tissue averaged 154.0 approximately 163.7% of the corresponding concentration in venous blood in the group receiving 600 mg but 78.8 approximately 86.2% in the group receiving 1,200 mg . This difference between the 2 groups was considered to reflect largely the difference in specimens collected . Thus, the concentration of CLDM in bone marrow tissue was interpreted as the amount of drug penetrating and remaining in bone marrow tissue and its adjacent area . The MIC75 of CLDM for clinical isolates were 0.20 micrograms/ml for S . aureus, 0.78 micrograms/ml for B . fragilis and 0.20 micrograms/ml for Peptostreptococcus spp . The concentrations of CLDM attained in bone marrow blood and tissue and its adjacent area after administration of 600 mg or 1,200 mg were thus sufficient to eliminate these organisms . The above results indicate that CLDM is a useful antibiotic for treatment and prevention of infection in orthopedics.

Jpn J Antibiot, 1986 Jan, 39(1), 116 - 20
{Clinical studies on the biliary excretion of mezlocillin, especially in cases with liver dysfunction}; Maeba T et al.; To investigate efficacy of mezlocillin (MZPC) in the treatment of biliary tract infection, the time course concentrations of MZPC in the bile of patients with, in particular, liver dysfunction were measured . MZPC concentrations in the bile decreased with the increase in the severity of liver dysfunction . However, the bile concentration was maintained more than 50 micrograms/ml even in cases of severe cholangitis with obstructive jaundice . These results indicate that MZPC is an useful antibiotic for the treatment of biliary tract infection.

J Membr Biol, 1986, 89(3), 251 - 67
Transport of alkali cations through thin lipid membranes by (222)C10-cryptand, an ionizable mobile carrier; Castaing M et al.; The kinetics of K+ and Na+ transport across the membrane of large unilamellar vesicles (L.U.V.) were compared at two pH's, with two carriers: (222)C10-cryptand (diaza-1,10-decyl-5-hexaoxa-4,7,13,16,21,24-bicyclo{8.8.8.}+ ++hexacosane) and valinomcyin, i.e . an ionizable macrobicyclic amino polyether and a neutral macrocyclic antibiotic . The rate of cation transport by (222)C10 saturated as cation and carrier concentrations rose . The apparent affinity of (222)C10 for K+ was higher and less pH dependent than that for Na+ but resembled the affinity of valinomycin for K+ . The efficiency of (222)C10 transport of K+ decreased as the pH fell and the carrier concentration rose, and was about ten times lower than that of valinomycin . Noncompetitive K+/Na+ transport selectivity of (222)C10 decreased as pH, and cation and carrier concentrations rose, and was lower than that of valinomycin . Transport of alkali cations by (222)C10 and valinomycin was noncooperative . Reaction orders in cation n(S) and carrier m(M) varied with the type of cation and carrier and were almost independent of pH; n(S) and m(M) were not respectively dependent on carrier or cation concentrations . The apparent estimated constants for cation translocation by (222)C10 were higher in the presence of Na+ than of K+ due to higher carrier saturation by K+, and decreased as pH and carrier concentration increased . Equilibrium potential was independent of the nature of carrier and transported cation . Results are discussed in terms of the structural, physiocochemical and electrical characteristics of carriers and complexes.

Chemotherapy, 1986, 32(2), 142 - 7
Enhancement of NK-cell activity in normal and tumor-bearing mice after administration of aclacinomycin; Andrade Mena CE et al.; Aclacinomycin (ACM) a new cytotoxic antibiotic employed in cancer chemotherapy, can either enhance or inhibit the NK-cell activity of the immune system, depending on the dose administered . A single intraperitoneal injection of 2-4 mg/kg of ACM augments the cytolytic activity by spleen and peritoneal exudate cells of normal mice and spleen cells depleted of nylon-adherent cells and peritoneal exudate cells of tumor-bearing mice . In contrast to the stimulatory effect of NK-cell activity by low doses of ACM, a single injection of 8 mg/kg of this agent leads to depression in the level of NK-cell activity in both normal and tumor-bearing animals . We suggest that the mechanism through which the ACM enhances NK-cell activity may be through the deletion of a suppressor cell population acting on the NK cells.

Infect Control, 1986 Jan, 7(1), 16 - 22
Candidal suppurative peripheral thrombophlebitis: recognition, prevention, and management; Walsh TJ et al.; Candida species are seldom considered as a cause of suppurative peripheral thrombophlebitis . During a 15-month period in a 291-bed acute-care hospital, candidal suppurative peripheral thrombophlebitis developed in seven patients . All patients had fever, a tender palpable cord, and Candida species isolated from resected veins and/or pus expressed at the catheter entrance site . Four patients had candidemia . None were neutropenic or recipients of corticosteroids . All had concomitant or preceding bacterial infections, and had received a median of 5 antibiotics (range 3 to 9) for at least 2 weeks . Five of seven had documented preceding candidal colonization associated with broad spectrum antibiotic therapy . Catheter sites had not been routinely rotated and local catheter site care was deficient . Risk factors of antibiotics and duration of hospitalization were fewer in patients with bacterial suppurative thrombophlebitis . Combined segmental venous resection and intravenous amphotericin B appears to be the most rational therapy for this nosocomial fungal infection.

J Arthroplasty, 1986, 1(3), 165 - 8
The addition of tobramycin to contrast bone cement . Effect on flexural strength; Bargar WL et al.; Samples of polymethylmethacrylate (PMMA) bone cement were polymerized in vitro with no additives and with the following additives: methylene blue dye, tobramycin, methylene blue plus tobramycin . After storage for 7 days in saline, samples were tested to failure in three-point bending . Addition of the antibiotic significantly weakened the cement (to 87% of control) . However, the combination of tobramycin plus methylene blue was no weaker than tobramycin alone, suggesting that addition of both dye and antibiotic to bone cement is probably a reasonable clinical practice.

Ital J Surg Sci, 1986, 16(4), 261 - 7
Acute cholangitis: diagnostic and therapeutic problems; Basoli A et al.; A retrospective study was carried out, analyzing the diagnostic and therapeutic problems in 80 patients with acute cholangitis at the time of hospitalization . 23% of the 17 patients with pus in the bile duct showed Reynolds' pentad, which was observed in 10% of patients with nonsuppurative acute cholangitis . Common bile duct lithiasis was responsible in 80% of cases presenting with Reynolds' pentad and in 66% of postoperative mortality . In 75% of patients with tumors, the clinical picture showed a rapid development following PTC . 79% of patients responded positively to antibiotic therapy with subsequent elective surgery, while in 21% of patients who did not respond to antibiotic therapy, biliary drainage was the treatment of choice . Mortality in patients with shock or hypotension was 30% while it was 17% in those undergoing early (less than 72 hours) surgery . On the basis of the results, it is concluded that, since it is not possible to assess preoperatively whether a patient belongs to the group of suppurative acute cholangitis or to that of nonsuppurative acute cholangitis, the different severity of the clinical picture should be based on clinical and biochemical parameters . The most severe developments were observed in common bile duct lithiasis or in patients with tumors who underwent PTC . In case of failure to respond to antibiotic therapy, decompression was shown to be the most suitable treatment . The mortality rate is related to the severity of the clinical picture (presence or not of shock) as well as to a prompt surgical treatment.

Cancer Chemother Pharmacol, 1986, 18(2), 117 - 23
Comparative nephrotoxicity of carboplatin and cisplatin in combination with tobramycin; Bregman CL et al.; The nephrotoxic potentials of cisplatin and carboplatin, alone and in combination with the aminoglycoside antibiotic tobramycin, were compared in male rats . Sixty (60) male Sprague-Dawley rats were divided into six groups of ten rats each and received the following treatments: Group I, saline; group II, cisplatin (5 mg/kg); group III, cisplatin (5 mg/kg) + tobramycin (50 mg/kg); group IV, carboplatin alone (50 mg/kg); group V, carboplatin (50 mg/kg) + tobramycin (50 mg/kg); and group VI, tobramycin alone (50 mg/kg) . Carboplatin and cisplatin were each administered as a single i.v . injection on day 1 . Tobramycin was administered i.-m . once daily on days 1-5 . All rats were euthanatized on day 6 . Smaller body weight gains occurred in groups II-V than in saline controls . Serum urea nitrogen (BUN) levels recorded on day 6 were elevated in group III . BUN values of all other groups were normal . Histopathologic examination of kidneys revealed acute tubular injury in rats treated with cisplatin, whether alone or in combination with tobramycin, and in carboplatin/tobramycin-treated rats . Carboplatin and tobramycin, when administered separately, were not nephrotoxic . The combination of cisplatin and tobramycin proved to be the most nephrotoxic treatment.

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