Berl Munch Tierarztl Wochenschr, 1989 Sep 1, 102(9), 303 - 10 {Entropion in newborn lambs}; Lamprecht H et al.; The Entropion in newborn lambs could be proved so far in 8 sheep-breeds and 7 cross-breeds out of 33 flocks in the Federal Republic of Germany . In our patients the Entropion was found at the lower eyelid only . The owners of the animals often mistake the Entropion for an ophthalmia . An early diagnosis and an early beginning of the therapy keep the expenditure of treatment small and shorten the period of treatment; therefore examination is commendable within a short time after birth . Female lambs get clearly more often affected than male ones (Gynecotropia) . In small pure-bred flocks with only one breeding-ram (and also in breeds with a limited population) the percentage of suffering lambs is higher than in large and crossed flocks with several rams and in large populations (except the breed "Heidschnucke") . In agreement with the literature it must be supposed that different genes are responsible for the Entropion . The selection of ill animals and those which are suspected of transmitting the disposition is evidently appropriate to lower the number of attacks of illness within a population considerably . All 47 affected eyes of 32 lambs were treated . Low degrees of Entropion were healed by repeated manual eversion plus application of antibiotic eye-ointment . In middle and high degrees of Entropion the application of Michel-wound-clamps on 23 of 26 eyes was successful; antibiotic eye-ointment was applied here, too; additionally these lambs prophylactically got 2000 I.U . of Tetanus-antitoxin.(ABSTRACT TRUNCATED AT 250 WORDS) Am J Vet Res, 1989 Sep, 50(9), 1486 - 8 Treatment of Brucella melitensis infection in mice by use of liposome-encapsulated gentamicin; Hernandez-Caselles T et al.; Liposomes with entrapped gentamicin were used to treat mice with infection attributable to Brucella melitensis . Liposomes bearing positive charge and formed by egg yolk lecithin, cholesterol, and stearylamine were effective in the elimination of B melitensis residing in liver and spleen . Negatively charged liposomes, formed by egg yolk lecithin, cholesterol, and dicetyl phosphate were also effective in suppression of the infection in liver, but were less so in suppression of the infection in the spleen . Free gentamicin was less effective than the encapsulated antibiotic . At 20 hours after administration of gentamicin encapsulated in liposomes, the gentamicin concentrations in liver and spleen were similar, regardless of the charge of the liposomes--neutral, positive, or negative . However, positively charged liposomes were more efficient than were other liposome types for the treatment of brucellosis caused by B melitensis. J Neurol, 1989 Sep, 236(6), 322 - 8 Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years; Kruger H et al.; In 1987, follow-up studies were conducted on 72 patients who had had meningoradiculitis and encephalomyelitis (8 patients) due to Borrelia burgdorferi 5-27 years previously . These patients had not been treated with antibiotics, either during the acute disease or during the interval prior to follow-up studies . The patients had exhibited the typical symptoms of Bannwarth's syndrome during the acute phase . At the follow-up studies, 33 patients showed no, and 23 only mild, clinical residual symptoms including normal CSF findings and low-positive serum IgG borrelia antibody titres (IFT; ELISA) . Three patients without sequelae exhibited persistent intrathecal secretion of oligoclonal B . burgdorferi-specific CSF IgG antibodies (Immunoblot; positive borrelia CSF IgG antibody titres) . Thirteen patients exhibited mild-to-medium sequelae with persistent intrathecal formation of oligoclonal B . burgdorferi-specific CSF IgG antibodies, up to 21 years after the acute illness . This persistence can be interpreted as an "immunological scar syndrome" . Our follow-up studies appear to indicate that neurological manifestations of B . burgdorferi infections are generally (with few exceptions) of a benign nature . Most patients can be classified as having been cured without antibiotic therapy . No late manifestations of chronic progressive CNS borreliosis comparable to that of neurosyphilis have been seen following acute untreated neuroborreliosis. In Vitro Cell Dev Biol, 1989 Sep, 25(9), 800 - 5 The application of renal cells in culture in studying drug-induced nephrotoxicity; Williams PD; Kidney cells in culture represent one of many in vitro approaches for studying drug-induced nephrotoxicity . Potential advantages of cell culture systems compared to more traditional in vitro models include a) the ability to examine direct effects at the cellular level, b) extended viability, c) ability for long-term storage, and d) capabilities for automation . Primary cultures of kidney tubules as well as cell lines of kidney origin are currently under evaluation as model systems for the assessment of nephrotoxicity . The application of two renal cell systems, rabbit primary proximal tubule cultures and the pig kidney cell line, LLC-PK1, in studying mechanisms of drug-induced nephrotoxicity is described in this communication . Potentially valuable insights into the renal pathogenesis associated with the antitumor agent, cis-diamminedichloroplatinum II, and the aminoglycoside antibiotic, gentamicin, have been obtained utilizing these renal cell models . Challenges in renal cell culture involve the characterization and maintenance of differentiated properties and the development of technologies to a) study bidirectional transport-toxicity of drugs, and b) provide a dynamic vs . static fluid environment as in vivo . Despite these unique challenges as well as the universal challenges involved in extrapolating any in vitro data to the in vivo situation, recent studies indicate that renal cells in culture are useful in the elucidation of mechanisms of drug-induced renal injury. In Vitro Cell Dev Biol, 1989 Sep, 25(9), 776 - 83 Primary cultures of rabbit renal proximal tubule cells: I . Growth and biochemical characteristics; Aleo MD et al.; Before the usefulness of a new in vitro model can be ascertained, the model must be properly defined and characterized . This study presents the growth rate and biochemical characteristics of rabbit renal proximal tubule cells in primary culture over a 2-wk culture period . When grown in a hormonally defined, antibiotic-free medium these cells form confluent monolayer cultures within 7 d after plating . Multicellular dome formation, an indicator of transepithelial solute transport, was expressed after confluent cultures were formed . The activity of the cytosolic enzyme, lactate dehydrogenase, and the lysosomal enzyme, N-acetyl-glucosaminidase, increased 14- and 2-fold during the first 8 d of culture, respectively . In contrast, the activity of a brush border enzyme, alkaline phosphatase, decreased 85% within the first 8 d of culture . Release of these enzyme markers into the culture medium, which are routinely used to measure cytotoxicity, stabilized after 8 d in culture . The ratio of cellular protein to DNA changed according to the state of cellular growth . Values rose from 0.035 mg protein/micrograms DNA in preconfluent cultures to 0.059 mg protein/micrograms DNA in confluent cultures . These results document the characteristics of a primary proximal tubule cell culture system for future studies in in vitro toxicology. Fam Pract, 1989 Sep, 6(3), 210 - 6 Health complaints and drug consumption during the first 18 months of life; Hakansson A; Medical events of the first 18 months of life were studied in a group of 129 infants . Their medical files held at the child welfare clinic and at the surgery of the district physician as well as at the ear, nose and throat and paediatric departments were scrutinized . The parents were interviewed when their infants had reached an age of 18 months . The 129 infants were brought to the district nurse or doctor on a total of 2804 occasions . The majority of these visits were routine health checks . During the period in question, 57% needed medical attention for upper respiratory tract infection and 29% for acute otitis media . Most of the infants had been given the non-prescription remedies paracetamol and nose drops . Altogether 64% had received some form of antibiotic . A positive correlation was found between the number of visits as a patient made by the mother during her pregnancy and the number of visits on behalf of her baby during its first 18 months. Eur J Epidemiol, 1989 Sep, 5(3), 355 - 62 Traveller's diarrhea among Austrian tourists to warm climate countries: II . Clinical features; Kollaritsch H; The syndrome "Traveller's Diarrhea" (TD) is important for tourists travelling to warm-climate countries . In this study a worldwide survey on the clinical features of enteritis among 1,455 Austrian tourists is reported . The clinical parameters of TD show that this disease exhibits a very uniform clinical course which is not influenced by different regions with considerable differences in aetiology or by travel-associated parameters such as accommodation, travel style and individual dietary hygiene: TD starts mainly at the end of first week of the stay and the average duration of illness is 3.6 +/- 2.7 days . Watery and mucous stools were reported by 99% of patients with a frequency of 4 bowel movements per day, while bloody diarrhea occurred very rarely . However, 57.2% of patients suffered from abdominal cramps, less than one third of patients reported nausea and/or vomiting and fever accompanied the acute disease in 13% . Symptoms indicate that TD should not be considered a severe disease . The diarrheal illness will show the characteristics of an enteroinvasive disease only in rare cases . Treatment of TD is discussed: symptomatic or other non-antibiotic agents are preferable as antibiotics will only occasionally be necessary for treatment of an illness with a self-limiting character . For prophylaxis of TD, the preferable way to resolve the problem of TD in international travel, very few effective preparations are currently available, emphasizing the need for extensive research in this field. J Am Vet Med Assoc, 1989 Sep 1, 195(5), 603 - 5 Field trial of theophylline in cattle with respiratory tract disease; McKenna DJ et al.; A field trial was conducted to determine the efficacy of theophylline in relieving respiratory distress associated with bovine respiratory disease complex (shipping fever) . Theophylline (as aminophylline capsules) was administered PO at a dosage of 28 mg/kg of body weight daily for 3 days to 20 calves with naturally acquired disease . Twenty similarly affected calves from the same group were given a placebo, and all calves were administered antibiotics concurrently . Respiratory rate and rectal temperature decreased and physical appearance improved in both groups of calves and was attributed to antibiotic administration or to natural remission of the disease . Five of the calves administered theophylline died; however, no calves administered the placebo died . Plasma theophylline concentration was greatly increased, compared with that determined in clinically normal calves in a pilot study . Bovine respiratory tract disease and/or concurrent antibiotic administration appear to cause such a rapid accumulation of lethal concentration of theophylline that its use should be restricted to hospitals capable of monitoring plasma theophylline concentration. Biopolymers, 1989 Sep, 28(9), 1585 - 96 Aggregation of amphotericin B in the presence of gamma-cyclodextrin; Kajtar M et al.; The macrolide antibiotic amphotericin B (AmB) forms an inclusion complex with gamma-cyclodextrin (gamma-CDx), resulting in a molecularly dispersed state of the drug . The state of aggregation of AmB in different solvents has been studied by absorption (uv-vis) and CD spectroscopy . While in aqueous solutions AmB forms colloid-like multimolecular aggregates, in the presence of gamma-CDx true solutions can be prepared, which show similar spectral properties as AmB dissolved in organic solvents . The AmB-gamma-CDx complex can be isolated as an amorphous, stable, water-soluble powder, indicating that gamma-CDx is a good carrier for the solubilization of this antibiotic . Using gamma-CDx as a carrier, the danger of precipitation of the drug during parenteral or intravenous administration can be largely reduced. Proc Natl Acad Sci U S A, 1989 Sep, 86(17), 6626 - 9 K+/H+-antiporter nigericin arrests DNA synthesis in Ehrlich ascites carcinoma cells; Margolis LB et al.; Acidification of the cytoplasm of Ehrlich ascites carcinoma cells to pH 6.3 arrests DNA synthesis in these cells . Such an effect can be achieved by incubating the cells at pH 6.2 or by adding low concentrations of the K+/H+ antiporter, the antibiotic nigericin, at neutral pH . Glucose and anaerobiosis potentiate the nigericin effect . The inhibition of DNA synthesis by nigericin occurs without any significant decrease in the ATP concentration and in the mitochondrial membrane potential . The DNA synthesis inhibition is caused neither by a decrease in the intracellular {K+} nor by an increase in the intracellular {Na+} accompanying the nigericin effect (at least at low concentrations of the antibiotic) . Nigericin should thus be regarded as a type of a cytostatic primarily affecting intracellular pH. Proc Natl Acad Sci U S A, 1989 Sep, 86(17), 6587 - 91 Crystal structure analysis of auromomycin apoprotein (macromomycin) shows importance of protein side chains to chromophore binding selectivity; Van Roey P et al.; The crystal structure of macromomycin, the apoprotein of the antitumor antibiotic auromomycin, has been determined and refined at 1.6-A resolution . The overall structure is composed of a flattened seven-stranded antiparallel beta-barrel and two antiparallel beta-sheet ribbons . The barrel and the ribbons define a deep cleft that is the chromophore binding site . The cleft is very accessible and in this structure is occupied by two 2-methyl-2,4-pentanediol and two water molecules . The overall shape of the binding site is similar to that of the analogue actinoxanthin . Highly specific side chains that are not conserved between different analogues extend into the binding site and may be important to the chromophore binding specificity. East Afr Med J, 1989 Sep, 66(9), 607 - 10 Evaluation of prophylactic use of tetracycline after evacuation in abortion in Harare Central Hospital; Seeras R; PIP: The purpose of this randomized, controlled study was to determine the efficacy of tetracycline as a prophylactic antibiotic therapy in treating nonseptic, incomplete abortion patients in Zimbabwe . In 1984, the gynecology emergency unit of Harare Central Hospital admitted 3240 cases of incomplete abortion, of which 2891 were nonseptic on admission . For this prospective study, patients presenting with nonseptic, incomplete abortion (n = 140) from February through May 1985 were recruited at Harare Central . These patients were randomly divided into treatment and control groups, and all patients received aseptic evacuation procedures . Following evacuation, the treatment group (n = 62) was given tetracycline (500 mg 4 times daily to be taken for a week) . The remainder (n = 78) acted as controls . Diagnosis for sepsis, based on defined parameters, was performed a week later by the author, who did not know the group to which the patient belonged . The majority of the patients in both groups were 15-24 years old and of parity 1-4 . An overall sepsis rate of 35.6% was obtained in this study . No significant difference in sepsis rates between treatment and control groups was noted . The apparent higher proportion of sepsis recorded in the treatment group (25/62, or 40.32%) in comparison to the control group (23/78, or 29.5%) was not significant . Although all patients insisted they took their drugs as instructed, further questioning and counting of remaining capsules revealed that the majority (82.6%) had not taken any or part of the course; the patients who did complete the course had not followed the instructions properly . Thus, the lack of significant reduction in the sepsis rate with the use of prophylactic tetracycline was thought to be due to poor compliance . The author argued that this was due to the young age, low socioeconomic status, and lack of understanding of the regimen among the patients . Thus, it is suggested that tetracycline treatment be replaced with a cheap, single-dose, hospital-administered prophylaxis regimen, such as doxycycline, that covers a wide range of organisms . J Cardiovasc Surg (Torino), 1989 Sep-Oct, 30(5), 782 - 5 Brucella endocarditis . Report of one case and review of the literature; Valliattu J et al.; We report a case of brucella endocarditis on a native aortic valve causing severe aortic regurgitation, uncontrolled heart failure and disseminated intravascular coagulopathy . The diagnosis was proven by positive serology, isolation of Brucella melitensis from preoperative blood cultures and excised valve . The patient was successfully treated with valve replacement and specific antibiotic therapy. Genetics, 1989 Sep, 123(1), 81 - 95 Nonrecombinant meiosis I nondisjunction in Saccharomyces cerevisiae induced by tRNA ochre suppressors; Louis EJ et al.; The presence of the tRNA ochre suppressors SUP11 and SUP5 is found to induce meiosis I nondisjunction in the yeast Saccharomyces cerevisiae . The induction increases with increasing dosage of the suppressor and decreases in the presence of an antisuppressor . The effect is independent of the chromosomal location of SUP11 . Each of five different chromosomes monitored exhibited nondisjunction at frequencies of 0.1%-1.1% of random spores, which is a 16-160-fold increase over wild-type levels . Increased nondisjunction is reflected by a marked increase in tetrads with two and zero viable spores . In the case of chromosome III, for which a 50-cM map interval was monitored, the resulting disomes are all in the parental nonrecombinant configuration . Recombination along chromosome III appears normal both in meioses that have no nondisjunction and in meioses for which there was nondisjunction of another chromosome . We propose that a proportion of one or more proteins involved in chromosome pairing, recombination or segregation are aberrant due to translational read-through of the normal ochre stop codon . Hygromycin B, an antibiotic that can suppress nonsense mutations via translational read-through, also induces nonrecombinant meiosis I nondisjunction . Increases in mistranslation, therefore, increase the production of aneuploids during meiosis . There was no observable effect of SUP11 on mitotic chromosome nondisjunction; however some disomes caused SUP11 ade2-ochre strains to appear white or red, instead of pink. Clin Lab Med, 1989 Sep, 9(3), 481 - 500 Genital Chlamydia infections; Ehret JM et al.; The past decade has seen a breakthrough in laboratory methods for the diagnosis of chlamydial infections . Antigen detection methods have made screening for C . trachomatis available in most clinical laboratories . These methods are highlighted and evaluated . Current culture methods and the antibiotic susceptibility of C . trachomatis are also discussed. South Med J, 1989 Sep, 82(9), 1147 - 52 Lyme disease: a confusing multisystem borreliosis; Lane KL et al.; Lyme disease, a tick-borne infection caused by the spirochete Borrelia burgdorferi, involves many organ systems . Three clinical stages of involvement have been described; patients with the disease may have cutaneous, arthritic, neurologic, or cardiac symptoms, or a constellation of manifestations . Specific antibody testing and antibiotic agents are available for Lyme disease, but a high index of suspicion must be exercised to recognize atypical manifestations. Respir Med, 1989 Sep, 83(5), 429 - 31 Long term venous access using a totally implantable drug delivery system in patients with cystic fibrosis and bronchiectasis; Ball AB et al.; A completely implantable, subcutaneous, venous access system (Port-a-Cath) has been used for antibiotic therapy in 26 patients with cystic fibrosis or bronchiectasis over a period of 45 months . During this period there were ten complications in eight patients and in four patients all or part of the system had to be replaced . Nevertheless, the actuarial median functional survival of the implanted system exceeded 30 months . The Port-a-Cath system provides longer periods of venous access and has a lower complication rate than conventional, percutaneous central venous lines. Clin Exp Dermatol, 1989 Sep, 14(5), 380 - 1 Recurrent blistering distal dactylitis of the great toe associated with an ingrowing toenail; Telfer NR et al.; We report a case of recurrent blistering distal dactylitis in a child . Although the skin returned to normal following antibiotic therapy, blistering later recurred . This recurrence was probably related to an associated ingrowing nail affecting the same digit. Antibiot Khimioter, 1989 Sep, 34(9), 687 - 91 {Individual schedule of administration of aminoglycosides with reference to anatomo-physiological and pathological factors}; Firsov AA et al.; Potentiality of designing individual dosage of sisomicin and gentamicin in regard to "patient factors" was estimated . 62 adult patients with various pulmonary diseases at the background of volemic disorders of diverse degrees were treated with the aminoglycosides under monitoring of their blood levels . Concentrations of sisomicin and gentamicin in serum 1, 3 and 6 hours after their single administration in a dose of 1 mg/kg were determined by HELC . The antibiotic pharmacokinetics was characterized by pronounced individual variability . The ratio of the difference between the upper and lower confidence limits to the average values of the steady-state volume of distribution, the total clearance and the mean residence time amounted to 70, 60 and 57 per cent respectively . To elucidate the cause of the variability multiple correlation analysis of the pharmacokinetic parameters by the "patient factors" was performed . The highest coefficient of the multiple correlation (r = 0.690) defined relation between the aminoglycoside concentration 1 hour after the injection and the hematocrit, globular volume and phase of the volemic disorders which was expressed in coded variables . The coefficient of the multiple correlation between the total clearance and the body surface area, concentrations of creatinine and urea in serum, hematocrit, circulating blood volume and the phase of the volemic disorders was equal to 0.439 . Therefore, the consideration of the above factors allowed to explain only 20 per cent of the observed individual variability of the pharmacokinetic parameters . In this connection mediated prediction of total clearance and subsequently individual dosage of the aminoglycosides by the "patient factors" was expedient only until the primary data on the pharmacokinetic monitoring were obtained. Antibiot Khimioter, 1989 Sep, 34(9), 682 - 4 {Quantitative analysis of rifampicin and 25-desacetylrifampicin in the plasma using high performance liquid chromatography}; Manuilov KK et al.; A procedure for determination of rifampicin and 25-desacetylrifampicin in plasma by HPLC was developed . The plasma proteins are precipitated by acetonitrile and the supernatant layer (50 microliters) is used for the assay under isocratic conditions on an analytical column 250 x 4.6 mm in size containing the reversed phase sorbent (C18) . The size of the precolumn is 50 x 4.6 mm . An UV detector (at lambda 335 nm) is used . For preparing the mobile phase 630 ml of methanol and 370 ml of 0.058 M sodium nitrite solution are mixed . The flow rate of the mobile phase is 40.7 ml/min . The assay duration is about 10 min . The retention time is 9.6 min for rifampicin and 6.5 min for 25-desacetylrifampicin . The minimum detectable amount of the antibiotic and its metabolite is 0.10 micrograms/ml . The standard curves of rifampicin and 25-desacetylrifampicin are linear within the concentration ranges of 0.5-100 and 0.5-10 micrograms/ml respectively . The procedure is useful in studies on pharmacokinetics of rifampicin and 25-desacetylrifampicin. Horm Metab Res, 1989 Sep, 21(9), 489 - 93 Actinomycin D inhibits the rapid increase in translatable calcitonin mRNA provoked by acute calcium stimulation; Segond N et al.; Calcium, injected to rats, elicits a rapid increase in translatable calcitonin mRNA, by acting probably at the post-transcriptional level, as no change in calcitonin mRNA could be detected by hybridization assay . In this study we have measured calcitonin mRNA extracted from rats subjected or not to acute hypercalcemia and pretreated or not with actinomycin D . Calcitonin mRNA was quantified by its ability to direct the synthesis of calcitonin (CT) precursors in a cell free system and by hybridization to a 32P cDNA probe specific for CT mRNA . Actinomycin D, injected 5 hours before calcium administration, decreased the incorporation of 3H adenine in liver and thyroid, but did not inhibit the rise in plasma levels of calcium and CT (measured by radioimmunoassay) . The antibiotic was able to inhibit the eightfold increase in translatable mRNA elicited by calcium administration in the control animals . Hybridizable CT mRNA levels were not modified by the treatments . Thus the increase in translatable CT mRNA after calcium stimulation is independent of CT secretion and is probably due to post-transcriptional modifications involving the expression of other gene(s). EMBO J, 1989 Sep, 8(9), 2717 - 25 Structure and deduced function of the granaticin-producing polyketide synthase gene cluster of Streptomyces violaceoruber Tü22; Sherman DH et al.; A 6.5 kb region of DNA from Streptomyces violaceoruber, which contains polyketide synthase (PKS) genes for production of the benzoisochromane quinone moiety of the antibiotic, granaticin, was cloned and sequenced . Of six open reading frames (ORFs) identified, four (ORFs 1-4) would be transcribed in one direction and two (ORFs 5 and 6) divergently from ORFs 1-4 . ORF1 and ORF2, which show evidence for translation coupling, encode (deduced) gene products which strongly resemble each other and the Escherichia coli fatty acid ketoacyl synthase (condensing enzyme), FabB . We conclude that ORF1 (which contains a characteristic cysteine residue) functions as a condensing enzyme, possibly as part of a heterodimeric protein including the product of ORF2 . The predicted ORF3 gene product strikingly resembles acyl carrier proteins (ACPs) of fatty acid synthase (FAS), particularly in the region of the active site motif, while the predicted ORF5 and ORF6 gene products resemble known oxidoreductases, suggesting that they function as reductive steps required during assembly of the granaticin carbon skeleton . Comparison of the deduced ORF4 gene product with available protein databases failed to elucidate its potential function . The overall conclusion is that the granaticin-producing PKS would consist of at least six separate enzymes involved in carbon chain assembly, thus resembling a Type II, rather than a Type I, FAS. J Clin Microbiol, 1989 Sep, 27(9), 2115 - 7 Comparison of three kinds of blood and two incubation atmospheres for cultivation of Bordetella pertussis on charcoal agar; Hoppe JE et al.; We compared the growth of Bordetella pertussis strains (n = 32) on antibiotic-free and cephalexin (40 micrograms/ml)-containing charcoal agar supplemented with 10% defibrinated horse blood, defibrinated sheep blood, or anticoagulant-containing human blood . Plates were incubated either in air or in an atmosphere with 5 to 10% CO2 . As assessed by mean colony numbers and rapidity of growth, normal air was preferable to CO2 enrichment for incubation . Growth on horse blood agar was more abundant and more rapid than on sheep blood agar, but the difference in general was not statistically significant . Human blood was clearly inferior to both horse and sheep blood. J Virol, 1989 Sep, 63(9), 3829 - 36 Cloning and expression of foreign genes in vaccinia virus, using a host range selection system; Perkus ME et al.; A simple selection system has been developed for the cloning and expression of open reading frames in vaccinia virus . The selection system is based on a conditional lethal (host range) mutant of vaccinia virus . A deletion mutant of the vaccinia virus WR strain was generated by insertion of the neomycin resistance gene from transposon Tn5 and selection with the antibiotic G418 . This deletion recombinant, vP293, lacked approximately 21.7 kilobases of DNA beginning 3.8 kilobases from the left end of the genome, vP293, was capable of plaquing on primary chicken embryo fibroblasts and two monkey cell lines (BSC-40 and Vero) but was defective in replication in the human cell line MRC-5 . Insertion of the host range gene K1L into vP293 restored the ability to grow on MRC-5 cells . A series of plasmids were constructed which in addition to the K1L gene contained a vaccinia virus early-late promoter, H6, followed by a unique polylinker sequence, translational initiation and termination signals, and an early transcription termination signal . These plasmids, pHES1 through 4, allowed for rapid single-step cloning and expression of any open reading frame when recombined in vivo with vP293 and scored for growth on MRC-5 cells. Derm Beruf Umwelt, 1989 Sep-Oct, 37(5), 183 - 5 {The dangers of olaquindox . Photoallergy, chronic photosensitive dermatitis and extreme increased photosensitivity in the human, hypoaldosteronism in swine}; Schauder S; The antibiotic olaquindox, an ingredient added to porker feed to increase overall performance, caused a photoallergic contact eczema and subsequently a chronic photosensitive dermatitis with increased UV-A- and UV-B-sensitivity in a breeder of small pigs . Through the use of sun creams he developed an additional (photo)allergic contact eczema to the sunscreens contained in the creams. Rev Med Chil, 1989 Sep, 117(9), 1023 - 8 {Abdominal actinomycosis: review apropos of 3 cases}; Martinez J et al.; Actinomycosis is a chronic bacterial infectious disease, characterized by multiple abscesses, draining sinuses and abundant dense fibrous tissue . The intra-abdominal variety is rarely found and difficult to diagnose . We report three cases of intra-abdominal actinomycosis successfully treated by surgery and by longterm antibiotic therapy . One patient had a liver actinomycosis and two had ileo-caecal disease . Pertinent literature is reviewed. G Chir, 1989 Sep, 10(9), 505 - 7 {Infections caused by central venous catheter used in surgery}; Mancini S et al.; The central venous catheters, now usually adopted in surgical patients, present some potential septic risks, and the longer the catheter is in place, the more dangerous it is . The authors report their experience on 130 central venous catheters, out of which 96 were used for TPN administration and 34 for monitoring purposes . The catheters were introduced through subclavian, internal jugular or basilic veins, in accordance with a standardized technique . The observed infection percentage, caused by the catheters, was 7.7%; the infection was easily controlled by the catheter removal and a proper antibiotic therapy . The only death, surely due to sepsis, was caused by Candida fungus in an immunosuppressed female patient . Therefore the authors stress the importance to prevent septic complications in order to avoid fatal ones. Indian J Exp Biol, 1989 Sep, 27(9), 757 - 60 Precocious desynapsis of XY-bivalent in mouse germinal cells: influence of mitomycin C on tumour-bearing and normal mice; Dey D et al.; A comparative study on the cytotoxic potential of anticancer-antibiotic mitomycin C has been made on tumour-bearing and normal mice considering precocious desynapsis of sex bivalent as parameter . The study indicates a strikingly differential effect of the drug on the phenomenon in two different types of mice . The administration of mitomycin C at therapeutic dose although enhances the frequency of precocious desynapsis of XY-bivalent in non-tumour (normal) mice to a significant extent (compared to control), the same drug at the same dose fails to produce a similar effect on tumour-bearing specimens . Discussions have been made on: (i) the probable cause for this differential effect, (ii) the mechanism of mitomycin action on precocious desynapsis of sex bivalent and, (iii) the possible significance of the findings in relation to cancer chemotherapy. Rev Med Interne, 1989 Sep-Oct, 10(5), 413 - 9 {Candida spondylodiscitis . Report of 2 personal cases and 28 cases from the literature}; Collet P et al.; Vertebral osteomyelitis caused by Candida spp . has recently been described and seems to be rare since only 30 cases have been published so far . Its clinical, laboratory and radiological features are identical with those on non-tuberculous bacterial spondylitis . It develops in subjects with poor general condition who underwent multiple surgical operations or received prolonged antibiotic therapy . The finding of Candida at needle biopsy of the since clinches the diagnosis . Serological tests might provide an earlier diagnosis and, above all, enable therapeutic effectiveness to be evaluated . In 27 of the 30 cases reported here, cure was obtained by prolonged infusions of antifungal drugs, chiefly amphotericin B and/or 5-fluorocytosine. Antimicrob Agents Chemother, 1989 Sep, 33(9), 1592 - 9 Growth phase dependency of chromatin cleavage and degradation by bleomycin; Moore CW et al.; Preferential cleavage of Saccharomyces cerevisiae chromosomes in internucleosomal (linker) regions and nonspecific degradation of chromatin by an anticancer antibiotic which degrades DNA were investigated and found to increase in consecutive stages of growth . Cleavage of DNA in internucleosomal regions and intensities and multiplicities of nucleosomal bands were dependent on drug concentration, growth phase of the cells, and length of incubation . Cellular DNA was least degraded during logarithmic phase . After cells progressed only one generation in logarithmic phase, low concentrations (6.7 x 10(-7) to 3.4 x 10(-6) M) of bleomycin produced approximately three to seven times more DNA breaks . Internucleosomal cleavage was highest, and the most extended oligonucleosomal series and extensive chromatin degradation were observed during stationary phase . It is concluded that the growth phase of cells is critical in determining amounts of the highly preferential cleavage in internucleosomal regions and overall breakage and degradation of DNA . Mononucleosomal bands were most intense, indicating the greatest accumulation of DNA of this size . Mean mononucleosomal lengths were 165.9 +/- 3.9 base pairs, in agreement with yeast mononucleosomal lengths . As high-molecular-weight chromatin was digested by bleomycin, oligonucleosomes and, eventually, mononucleosomes became digested . Therefore, it is also concluded that bleomycin degradation of oligonucleosomes and trimming of DNA linker regions proceed to degradation of the monosomes (core plus linker DNA). J Bacteriol, 1989 Sep, 171(9), 4792 - 8 An Escherichia coli mutant resistant to phleomycin, bleomycin, and heat inactivation is defective in ubiquinone synthesis; Collis CM et al.; A mutant of Escherichia coli, selected for resistance to the antibiotic and antitumor agent phleomycin, has been characterized, and the phleomycin resistance determinant has been identified . The mutant is equally resistant to bleomycins . The resistance to phleomycin is strongly dependent on the nature of the C-terminal amine of the drug, with the greatest resistance being shown to phleomycins and bleomycins with the most basic terminal amines . The mutation also confers resistance to the lethal effects of heating at 52 degrees C . Other characteristics of the phleomycin-resistant strain include a slow growth rate, an inability to grow on succinate as the sole carbon source (Suc- phenotype), cross resistance to aminoglycoside antibiotics, and a slight sensitivity to hydrogen peroxide, methyl methanesulfonate, and gamma-irradiation . Some of these characteristics, together with mapping data, suggested that the phleomycin resistance and Suc- determinant probably lies within the ubiF gene coding for an enzyme effecting a step in the biosynthesis of ubiquinone . The phenotypes of known mutants defective in this and other steps of the ubiquinone pathway were found to be closely similar to those of the original phleomycin-resistant strain. J Immunol, 1989 Sep 1, 143(5), 1580 - 3 FK-506, a potent novel immunosuppressive agent, binds to a cytosolic protein which is distinct from the cyclosporin A-binding protein, cyclophilin; Siekierka JJ et al.; A novel macrolide antibiotic, FK-506, isolated from Streptomyces tsukubaensis, has been shown to be a potent immunosuppressive agent in vivo and in vitro . FK-506 shares a number of immunosuppressive properties with the cyclic peptide, cyclosporin A (CsA), although 10 to 100 times more potent in this regard . These similarities suggest that both agents may share a similar mechanism(s) of action at the biochemical level . We have identified a cytoplasmic binding protein for FK-506 in the human T cell line, JURKAT, using {3H}FK-506 . The FK-506 binding protein has a mr of 10 to 12 kDa (as determined by gel filtration), is heat stable and does not bind CsA . This contrasts with the CsA binding protein, cyclophilin, in that cyclophilin is heat labile and has a mr of 15 to 17 kDa . Our data suggest that FK-506 binds to a low m.w . protein(s) in JURKAT cells, which is distinct from cyclophilin . This protein may mediate the immunosuppressive effects of FK-506 in T cells . In addition, our results suggest that the immunosuppressive activity of FK-506, as with CsA, is mediated by an intracellular mechanism. Minerva Chir, 1989 Aug 31, 44(15-16), 1825 - 9 {Considerations on the pre- and peri-operative preparations in surgery of the colon}; Pira L; The type and frequency of local postoperative complications after 265 elective colon-rectal operations occurring in 262 patients are described . The orthograde enema, which causes discomfort to the patients and a considerable amount of work for the nursing staff can be waived . Since the results obtained (11.5% local postoperative complications) are regarded as satisfactory and display no marked differences from the incidence with orthograde enema, the case for the combination of pre- and postoperative antibiotic infection prophylaxis is substantiated. Biochemistry, 1989 Aug 22, 28(17), 7097 - 101 Conformation and reactivity changes induced by N-methylkirromycin (aurodox) in elongation factor Tu; Balestrieri C et al.; Kirromycin and related antibiotics inhibit protein synthesis in bacteria by acting on elongation factor Tu (EF-Tu) . We have studied the effects of N-methylkirromycin (aurodox) on some molecular properties of this protein . The binding of the antibiotic causes a dramatic variation in the protein fluorescence emission spectrum with the appearance of a new maximum at around 340 nm . Addition of aurodox to trypsinized EF-Tu resulted in an emission spectrum similar to that of the denatured intact factor . Fluorescence lifetime analysis performed by a multifrequency phase fluorometer indicated that the fluorescence emission of the factor is heterogeneous with the major component having a lifetime near 4.8 ns in the absence and 6.6 ns in the presence of the antibiotic . These results were interpreted in terms of an antibiotic-induced environmental modification of the unique tryptophan residue of the protein leading to an increase in its quantum yield . However, aurodox did not modify the solvent exposure of this residue, as judged by fluorescence quenching experiments . Moreover, 1-anilino-8-naphthalenesulfonate (ANS) binding studies, as well as analysis of the protein reactivity toward the sulfhydryl group reagent 5,5'-dithiobis(2-nitrobenzoate) (DTNB), showed that, in the presence of aurodox, the behavior of the EF-Tu-GDP complex nears that of EF-Tu.GTP . These results strongly support the hypothesis that aurodox not only confers a "GTP-like" conformation to the EF-Tu.GDP complex but also produces a less stable folding of the protein around the tryptophan residue that may contribute to the multiple functional effects of this antibiotic. Pol Tyg Lek, 1989 Aug 21-28, 44(34-35), 792 - 4 {Cefoperazone in the treatment of infections in newborn infants}; Krzeska I et al.; The authors evaluated clinically cefoperazone (Cefobid-Pfizer)--an antibiotic of the III generation of cephalosporins--administering it in the form of monotherapy to 32 infected neonates and premature babies . A complete recovery was achieved im 25 neonates, i.e . 78.1%, out of which 76.5% were generalized infections . The result of therapy was doubtful in the remaining 7 babies (21.9%) . The drug was changed or the second antibiotic added . No decidedly unfavourable results (deaths) or adverse reactions necessitating withdrawal of the drug were observed . The authors compare this favourable results with the mortality rate of neonates prior to the introduction of the II and III generation cephalosporins . It was about 14%, then . Therefore, both +antibiotic monotherapy and cefoperazone enabling its use are worth wide popularization in neonates and small babies. Tijdschr Diergeneeskd, 1989 Aug 15, 114(15-16), 829 - 38 {Escherichia coli mastitis in cattle . I . Clinical diagnosis and epidemiological aspects}; Schukken YH et al.; The diagnostic aspects, incidence, risk factors and prevention of coliform mastitis are reviewed in the present paper . It is concluded that it is not possible to establish an accurate diagnosis of coliform mastitis, which is based on a specific clinical symptom differentiating it from other forms of mastitis . Not any single symptom or combination of symptoms is specific for coliform mastitis . The importance of coliform mastitis in dairy cattle showed a marked increase during the last few decades . Successful programmes for the prevention of mastitis reduced the importance of contagious organisms, but the overall incidence of mastitis has remained unchanged; therefore, the proportion of cases of coliform mastitis increased . The observation that coliform micro-organisms are common bacteria causing mastitis in herds with low bulk milk somatic cell counts implies that the future of the dairy industry will be associated with particular risks . Factors involving the risk of coliform mastitis are divided into cow level factors and herd level factors . The most important cow level factors were: leaking milk in between milkings, lesions of the teats and a reduced capacity of the immune system . Risk factors on the herd level include: the bedding material, the design of cubicles, exposure to daylight in summer-time, exposure to dirt and the use of dry-cow therapy . The possible role of antibiotic dry-cow treatment and teat dipping in colonisation resistance is discussed . Preventive programmes designed to reduce the incidence of coliform mastitis have not been very successful so far. Cancer, 1989 Aug 15, 64(4), 806 - 11 Nodular form of bleomycin-related pulmonary injury in patients with osteogenic sarcoma; Santrach PJ et al.; Bleomycin (BLEO), an antitumor antibiotic effective against a variety of malignancies, has been associated classically with a pulmonary toxic reaction producing diffuse interstitial fibrosis . However, BLEO-related pulmonary nodules have been reported recently, mostly in children and young adults treated for germ cell tumors . A different, apparent hypersensitivity reaction with prominent eosinophilic infiltrates has been seen in other patients . This report details the clinical history, radiographic features, and histopathologic condition of three patients with osteogenic sarcoma in whom pulmonary nodules developed during the course of their multiagent, BLEO-containing chemotherapy . The predominant histopathologic lesion was bronchiolitis obliterans-organizing pneumonia (BOOP); one patient had a significant eosinophilic infiltrate also . Pulmonary lesions developed in all of these patients after relatively low doses of BLEO (less than 200 mg) . All of these patients underwent open lung biopsy to establish the diagnosis . Reported cases of BLEO-induced pulmonary injury other than diffuse fibrosis are reviewed and comparisons are made with those in the current report . Also, suggestions are made for the management of these patients. Nippon Geka Gakkai Zasshi, 1989 Aug, 90(8), 1274 - 7 {Mycotic abdominal aneurysm requiring emergency operation due to sudden thrombotic obstruction: a case report}; Enomoto S et al.; A 59-year-old man was admitted with history of low grade fever, general malaise and low back pain . Physical examination showed a pulsatile mass in the mid-abdomen . There were slight leucocytosis, elevated BSR and CRP . Abdominal ultrasonography, CT and MRI revealed an abdominal aneurysm within which there was an intimal flap and thrombus . Though blood culture was not positive, antibiotic therapy was initiated on the presumption of a mycotic abdominal aneurysm . Six days after admission, he complained of numbness in the lower extremities and both femoral pulsations were not palpable . Emergency surgery was undertaken . The aneurysm was adhered to the IVC and the ileum and there was a large thrombotic mass in it . Aneurysmectomy and Y-graft interposition were done uneventfully . Pathology revealed marked thickness of the aorta and infiltration of lots of inflammatory cells . The culture of aneurysmal wall was negative . This is the very rare case because of sudden thrombotic occlusion of the mycotic abdominal aneurysm . Several important features of this disease have been also discussed. Jpn J Antibiot, 1989 Aug, 42(8), 1745 - 50 {Clinical studies on cefteram pivoxil in pediatrics}; Yokoyama M et al.; Cefteram pivoxil (CFTM-PI), a newly developed oral cephem antibiotic was administered to treat 16 children with various infections . The results were summarized as follows . 1 . The clinical responses were "excellent" in 7, "good" in 5, "fair" in 3 and "poor" in 1, with 75.0% efficacy rate . 2 . No side effects and no abnormal laboratory findings were observed. Jpn J Antibiot, 1989 Aug, 42(8), 1720 - 6 {Clinical evaluation of cefpiramide for infections in leukemia and related disorders}; Nakagawa H et al.; Forty one patients with infections associated with leukemia and related disorders were treated with cefpiramide (CPM) . In 26 patients among them, we were able to evaluate the effectiveness of CPM against infections . Fifteen patients were not evaluated, because 6 patients were subjected to additional therapy such as gamma-globulin and other antibiotics, 5 were prophylactically treated, 2 had fever episode which were retrospectively reviewed to be originated from tumor mass, 1 received too short a duration of administration of CPM (2 days) to evaluate its effectiveness, and 1 with whom no precise data were recorded . Excellent responses were observed in 10 patients (38.5%) and good responses in 6 (23.1%) among these 26, with a total efficacy rate of 61.5% . Whereas, we found only one patient who showed an unfavorable side effect out of 31 patients including the 26 and 5 other patients who were prophylactically treated . The side effect observed was a mild bleeding tendency occurred in 77 years old female at 11 days after CPM was administrated . The bleeding tendency was easily diminished with the cessation of CPM treatment and a parenteral use of vitamin K . These results suggest that CPM is an effective and safe antibiotic for the treatment of infections in patients with leukemia and related disorders. Nippon Kyobu Geka Gakkai Zasshi, 1989 Aug, 37(8), 1565 - 9 {Poststernotomy mediastinitis treated by early surgical intervention}; Oku T et al.; Poststernotomy mediastinitis in 67-year-old female was successfully treated by early operation after coronary artery revascularization using bilateral internal mammary arteries and gastroepiploic artery . Wider debridement including sternum, ribs, mediastinal fat and connective tissues, and transfer of rt-pectoralis major muscle flap into the mediastinum to obliterate the dead space was performed . The sternal wound was primarily closed without postoperative irrigation . The sternum was stayed open without using any artificial substitute . In conclusion, the early diagnosis and operation is the key for successful treatment of poststernotomy mediastinitis . Wider debridement including sternum and ribs with perioperative lavage by diluted povidone-iodine solution and antibiotic solution should be done aggressively, and the transfer of the major pectoral muscle flap and skin closure without postoperative irrigation is an effective method of choice . Additional reconstruction of anterior chest wall should be considered if necessary, when the inflammatory process is subsided. Helv Chir Acta, 1989 Aug, 56(3), 365 - 7 {Is there a thrombophlebitis or subcutaneous lymphangitis of the penis?}; Von Rutte B; Twelve patients suffering from subcutaneous dorsal induration of the penis were investigated . The diagnosis of a lymphangitis or thrombophlebitis depends on clinical features . It is of nonvenereal origin, and the treatment, if necessary, consists in local or systemic antiinflammatory or antibiotic therapy. Int J Clin Pharmacol Ther Toxicol, 1989 Aug, 27(8), 388 - 91 Epirubicin high-dose therapy in advanced breast cancer: preliminary clinical data . Epirubicin as a single agent in breast cancer; Neri B et al.; Of the new anthracycline derivatives, epirubicin is the antibiotic whose antitumor activity is comparable to that of doxorubicin while its cardiotoxicity is reduced by half . We therefore incorporated into our continuing study on anthracycline antitumor effects and toxicity a group of 22 evaluable patients, mean age 52 years, with advanced breast cancer, all of whom had previously undergone chemotherapy, radiotherapy and/or hormonal therapy . Epirubicin was administered at a dose of 120 mg/M2 every 3 weeks, for a maximum of 10 such cycles . The left ventricular ejection fraction (LVEF), determined by radionuclide ventriculography, was measured periodically in all patients . We observed 2 complete responses and 13 partial responses (CP + PR = 69%) of 61 weeks' mean duration; in 3 cases lesions remained stationary while the disease progressed in 4 patients . No patients died of acute toxicity . The main side effects were severe alopecia in 82% of the subjects and moderate degrees of nausea without vomiting in 41% . After 6 treatment cycles, 4 patients showed mild cardiotoxicity and at an epirubicin cumulative dose of 1,200 mg/M2 2 patients developed congestive heart failure (CHF) . Hematological toxicity was in no case so severe as to require a reduction in the dose but only a postponement of treatment by 3 to 5 days in 9% of cycles . Without increasing hematological or cardiac toxicity, epirubicin, at a dose of 120 mg/M2, has shown itself to be a highly effective agent against advanced breast cancer. Spine, 1989 Aug, 14(8), 808 - 11 Gunshot wounds to the spine associated with a perforated viscus; Roffi RP et al.; The cases of 42 patients with low-velocity gunshot wounds to the spine with an associated perforated viscus were reviewed . All viscus perforations occurred prior to the spinal injury . There were a total of 51 perforations, including 14 of the colon, 15 of the small bowel, 15 of the stomach, five of the esophagus, and two of the pharynx . All patients had significant neurologic deficits, with 23 patients suffering a complete neurologic injury . Average clinical follow-up was 18 months (range: 4-64 months) . Only three patients developed documented spinal or paraspinal infections . One case of acute meningitis occurred after an isolated stomach perforation, while two other patients developed psoas abscesses after colon injuries . The roles of initial antibiotic therapy and of early bullet removal were evaluated in regard to infection . An extended course of broad spectrum antibiotics combined with bedrest appeared to significantly reduce the risk of spinal or paraspinal infection as compared with a previous study . Early bullet removal did not appear to be a significant factor in the prevention of infection . Prospective studies are needed to accurately delineate the role of initial antibiotic therapy for the prevention of spinal infection in these injuries. J Pharm Sci, 1989 Aug, 78(8), 648 - 51 Non-micelle forming bile acids increase biliary gentamicin excretion in the rat; Oehler R et al.; To investigate whether non-micelle forming bile acids are able to increase biliary gentamicin excretion, male Sprague-Dawley rats were anesthetized with pentobarbital and fitted with a biliary fistula . After a control period of 30 min, dehydrocholate, taurodehydrocholate, or norursodeoxycholate were administered iv at doses of 2 or 10 mumol.min-1.kg-1 . Taurodehydrocholate increased bile flow and biliary gentamicin clearance similarly in a dose-dependent fashion . Its unconjugated analogue, in contrast, increased gentamicin clearance fourfold, while increasing bile flow only 1.6-fold . This suggests that other than purely osmotic phenomena were involved . This effect was even more marked for the short-chain bile acid, norursodeoxycholate . At a dose of 2 mumol.min-1.kg-1 it increased bile flow by 30%, but gentamicin clearance by 210%; a similar discrepancy between choleresis and gentamicin clearance was observed at the higher dose tested . It may be concluded that conjugated triketo bile acids increase biliary gentamicin clearance by osmotic choleresis . Unconjugated triketo bile acids and nor-bile acids, to an even greater extent, increase gentamicin clearance much more markedly than bile flow; other effects, such as the putative cholahepatic shunt pathway, are responsible for this phenomenon . This novel therapeutic principle might be useful in achieving therapeutic biliary antibiotic concentrations or in treating gentamicin intoxication in patients with renal insufficiency. Geriatrics, 1989 Aug, 44 Suppl A, 28 - 31 Treatment of nosocomial pneumonia: monotherapy versus combination therapy; Greco T; Pneumonia accounts for 15% of all nosocomial infections, and mortality case rates are as high as 60% . Aspiration of oropharyngeal flora is the most common antecedent to nosocomial pneumonia . Patients with chronic lung disease, depressed levels of consciousness, or who are intubated are at increased risk of developing pneumonia . We conducted two comparative, prospective studies using monotherapy with third-generation cephalosporins--the first comparing cefoperazone with combination therapy, and the second comparing cefoperazone monotherapy with ceftazidime monotherapy--for the treatment of nosocomial pneumonia in mildly to moderately ill patients . We found that both cefoperazone monotherapy and ceftazidime monotherapy were as effective as standard two-drug combinations (clindamycin/gentamicin or cefazolin/gentamicin) . When total antibiotic costs were compared, cefoperazone monotherapy was the least expensive regimen. J Pediatr Surg, 1989 Aug, 24(8), 729 - 32 Cholangitis after the Kasai operation for biliary atresia; Rothenberg SS et al.; One hundred seventy-nine episodes of cholangitis in 28 consecutive patients having a Kasai operation for biliary atresia during the past 3 1/2 years were analyzed . The diagnosis was made primarily on the basis of unexplained fever (greater than 38.0 degrees C) . An increase in serum bilirubin or a decrease in bile volume and in bile bilirubin concentration were often confirmatory, but other laboratory data including serum hepatic enzymes and blood and bile culture data were of little or inconsistent value . All patients were treated with systemic antibiotics . The best results were obtained with third-generation cephalosporins or imipenemcilastatin with the addition of aminoglycosides in recalcitrant cases . Antibiotic therapy was modified if defervescence did not occur within the first 24 hours . Cholangitis refractory to antibiotics was aggressively treated with pulse steroid therapy, and in some cases, operative intervention, both with good clinical success (60% and 73%, respectively). Int J Cardiol, 1989 Aug, 24(2), 173 - 7 Efficacy of aortic balloon valvoplasty: direct measurement of orificial area in a model with pulsatile flow; Sprigings DC et al.; The efficacy of balloon valvoplasty of calcific aortic stenosis remains controversial . We studied, therefore, 5 human aortic valves obtained at necropsy in a positive-displacement pulse duplicator which delivered stroke volumes of 40-100 ml with a quasiphysiological waveform of flow . All valves had three leaflets without commissural fusion and were preserved in antibiotic solution before study . Orificial area was planimetered from videotape of opening of the valve and varied with flow in all cases . Valvoplasty with a 20 mm diameter balloon had no effect on the orifice of the normal valve but increased the orifice of 2 mildly calcified valves from 0.70-1.77 cm2 (range) at baseline to 1.06-1.95 cm2 . In 2 valves with severe calcification of the leaflets, the orifice was increased from 0.31-0.82 cm2 to 0.73-1.07 cm2 . Dual balloon valvoplasty achieved a variable but small further increase in orificial area . No valve showed tears of the leaflets or fracture of calcific deposits after valvoplasty . We conclude that balloon valvoplasty can acutely increase orificial area, independently of any change in stroke volume . In valves without commissural fusion, its mechanism appears to be an increase in the pliability of the leaflets which does not require macroscopic fracture of calcific deposits. Urology, 1989 Aug, 34(2), 89 - 92 Conservative management of renal carbuncles in children; Whitfield JD et al.; Renal carbuncles have traditionally been treated with surgical drainage and appropriate antibiotic therapy . Recently, 2 pediatric patients with well-documented renal carbuncles were treated with antibiotic therapy alone . Close follow-up documented complete resolution in both cases . Late studies showed no evidence of renal scarring or functional compromise. Ann Emerg Med, 1989 Aug, 18(8), 856 - 62 Analysis of emergency department management of suspected bacterial meningitis; Talan DA et al.; Previous studies of emergency department management of bacterial meningitis have indicated that there are often long delays before initiation of antibiotics . The purpose of our study was to determine whether these delays were related to specific aspects of patient management . From 1981 through 1988, we retrospectively reviewed the medical records of 122 patients primarily evaluated in the ED and admitted for suspected bacterial meningitis at a university (55) and a community (67) hospital . The median time (interquartile range) from ED registration until initiation of antibiotics (time to antibiotics) was 3.0 hours (1.6 and 4.3 hours, respectively) (total range, 0.5 to 18 hours) . The time to antibiotics was not significantly related to the time of ED registration . Ninety percent of the total time to antibiotics occurred after the initial physician encounter . Time to antibiotics was significantly (P less than .00005) longer for patients in whom computed tomography scan and/or laboratory analysis of cerebrospinal fluid preceded initiation of antibiotics compared with patients in whom antibiotic administration was not contingent on the results of these procedures (4.3 {3.2 and 6.0} versus 1.9 {1.2 and 3.4} hours, respectively) . Also, time to antibiotics was significantly (P less than .00005) longer for patients in whom antibiotics were initiated on the ward as compared with in the ED (4.5 {3.5 and 6.8} versus 2.2 {1.4 and 3.5} hours, respectively) . We conclude that long delays exist in the ED before initiation of antibiotics for cases of suspected bacterial meningitis, and that in general these delays appear to be physician generated and to a great extent potentially avoidable. J Surg Res, 1989 Aug, 47(2), 183 - 8 Glucan enhances survival in an intraabdominal infection model; Bowers GJ et al.; The immunomodulator glucan exists in two forms, particulate (glucan-P) and soluble (glucan-F) . Both preparations of glucan, either alone or in combination with antibiotic therapy, were evaluated for their ability to augment survival in rats following cecal ligation and puncture (CL/P) . Adult male rats were infused once daily for 5 consecutive days with either glucan-P (10 mg/kg), glucan-F (10 mg/kg), or 5% (w/v) dextrose in water . Three days later all rats underwent CL/P . Postoperatively, the rats received (a) no therapy, (b) saline (1 ml subcutaneously every 12 hr) or (c) ampicillin (33 mg/kg subcutaneously every 12 hr) for 7 days . Without any associated pre-or postoperative treatment, CL/P was associated with an 85% 7-day mortality . Neither glucan preparation alone significantly altered this mortality . Administering ampicillin postoperatively decreased the mortality to 53% (P less than 0.001 vs untreated controls) . When postoperative ampicillin therapy was combined with preoperative glucan treatment, the mortality was reduced even further (26% for glucan-P, 21% for glucan-F; P less than 0.02 vs ampicillin-treated controls) . We conclude from these results that (i) neither glucan preparation alone effectively enhances survival following CL/P when using the doses and administration schedule employed herein, (ii) both glucan-P and glucan-F do act synergistically with antibiotics to enhance survival in this rat model of polymicrobial sepsis, and (iii) in this particular model, nontoxic glucan-F is as efficacious as glucan-P. J Am Acad Dermatol, 1989 Aug, 21(2 Pt 2), 410 - 3 Leukemia cutis presenting as a scrotal ulcer; Zax RH et al.; A patient with acute nonlymphocytic leukemia developed a painful scrotal ulcer thought initially to be caused by infection . The lesion failed to heal with oral antibiotic therapy and local wound care . Histopathologic examination of a biopsy specimen revealed an infiltrate of leukemic cells . This cutaneous lesion heralded the relapse of acute myelogenous leukemia . A review of the literature indicates that acute nonlymphocytic leukemia rarely presents as an ulcer or on the genitalia, thus emphasizing the uniqueness of this case regarding morphology, and site of presentation . To our knowledge, this is the first case of leukemia cutis presenting as a scrotal ulcer . Therefore leukemia cutis should be added to the differential diagnosis of chronic genital ulcers . Also, because a variety of skin lesions may signify the relapse of leukemia, any skin lesion in a patient with leukemia should be examined by biopsy. Chest, 1989 Aug, 96(2), 419 - 20 Reversion of mitral valve preclosure in acute aortic insufficiency secondary to infective endocarditis; Rozich JD et al.; A 59-year-old man presented with culture-negative endocarditis . Serial echocardiographic/Doppler studies disclosed progressive aortic insufficiency with resultant premature closure of the mitral valve . At the time the patient developed PMVC he was considered for emergent aortic valve replacement; ultimately, however, he was deemed inoperable because of his underlying medical problems . Surprisingly, the patient gradually improved on antibiotic therapy alone, with subsequent hemodynamic stabilization and reversion of the PMVC . This case represents the first description of reversion of PMVC in a medically treated patient with severe aortic insufficiency secondary to infective endocarditis, and underscores the importance of basing management decisions concerning aortic valve replacement in infective endocarditis upon the entire constellation of clinical findings rather than a single echocardiographic sign. J Neurochem, 1989 Aug, 53(2), 442 - 7 Characterization of the effect of monensin on gamma-amino-n-butyric acid release from isolated nerve terminals; Sitges M; The action of the polyether antibiotic monensin on the release of gamma-{3H}amino-n-butyric acid {( 3H}GABA) from mouse brain synaptosomes is characterized . Monensin enhances the release of this amino acid transmitter in a dose-dependent manner and does not modify the efflux of the nontransmitter amino acid alpha-{3H}aminoisobutyrate . The absence of external Ca2+ fails to prevent the stimulatory effect of monensin on {3H}GABA release . Furthermore, monensin is less effective in stimulating {3H}GABA release in the presence of Ca2+ . The releasing response to monensin is absolutely dependent on external Na+ . The blockade of voltage-sensitive Na+ or Ca2+ channels does not modify monensin-induced release of the transmitter . Also, the blockade of the GABA uptake pathway fails to prevent the stimulatory effect of monensin on {3H}GABA release . Although monensin markedly increases Na+ permeability in synaptosomes, these data indicate that the Ca2+-independent monensin-stimulated transmitter release is not mediated by the Na+-dependent uptake pathway . It is concluded that the entrance of Na+ through monensin molecules inserted in the presynaptic membrane might be sufficient to initiate the intraterminal molecular events underlying transmitter release. J Med Assoc Thai, 1989 Aug, 72(8), 465 - 8 Pulmonary sequestration: ultrasonographic visualization of feeding artery; Tritrakarn A; An intralobar pulmonary sequestration was diagnosed by ultrasonography in a child presenting with chronic respiratory infection . Chest radiograph showed multicystic infiltration in the left lung base . This was diagnosed as cystic bronchiectasis and failed to clear up in spite of adequate antibiotic therapy . Ultrasound (real-time) examination suggested pulmonary sequestration, and an aberrant blood supply was demonstrated . Subsequent angiography, surgery and pathological examination of the resected segment confirmed the diagnosis. J Reprod Med, 1989 Aug, 34(8 Suppl), 605 - 9 Pelvic inflammatory disease; Spence MR; Pelvic inflammatory disease (PID) is a genital tract infection that affects a predominantly young and sexually active population . While its exact pathogenesis has yet to be determined, it appears to be caused by several micro-organisms that develop in response to one or more of the following: foreign bodies, such as intrauterine contraceptive devices, retained tampons and douching solutions, and surgery, such as endometrial biopsy and hysterosalpingography . The most common risk factor for PID is multiple sexual partners . The disease is associated with infertility, sterility and adverse pregnancy outcomes . Management calls for aggressive antibiotic therapy and the temporary suspension of sexual activity. Br J Surg, 1989 Aug, 76(8), 821 - 4 Surgical management of neutropenic enterocolitis; Koea JB et al.; Three cases of histologically confirmed neutropenic enterocolitis, each presenting as an acute abdomen in patients with leukaemia are presented . All three patients presented with fever and abdominal pain within 14 days of completing a course of chemotherapy . Signs of peritonitis localized to the right iliac fossa developed in each patient, in spite of aggressive antibiotic therapy and bowel rest . All three patients were found to have non-viable caecum at laparotomy and were treated by right hemicolectomy . Primary ileocolic anastomosis was performed in one patient, who recovered following a stormy postoperative course owing to sepsis . Two patients underwent formation of an ileostomy with distal mucous fistula and each recovered with minimal postoperative complications; secondary anastomosis was performed electively in both cases . The difficulty in diagnosing neutropenic enterocolitis preoperatively is discussed and the place of non-operative management is reviewed but we recommend surgical intervention as a means of ensuring removal of a localized septic focus until marrow regeneration occurs. Neurology, 1989 Aug, 39(8), 1118 - 20 Latent Lyme neuroborreliosis: presence of Borrelia burgdorferi in the cerebrospinal fluid without concurrent inflammatory signs; Pfister HW et al.; Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, was isolated from the CSF of a patient with elevated serum IgG antibody titers against B burgdorferi and a history of multiple tick bites . The absence of concurrent inflammatory signs of CSF as well as intrathecal antibody production indicates a phase of latent Lyme neuroborreliosis in which no tissue infection or reaction has yet occurred . Bilateral tinnitus was the only clinical symptom in this patient . The persistence of the bilateral tinnitus after antibiotic therapy did not support a causal relationship between this symptom and the borrelial infection. J Bone Joint Surg Am, 1989 Aug, 71(7), 994 - 1004 Reconstruction of large diaphyseal defects, without free fibular transfer, in Grade-IIIB tibial fractures; Christian EP et al.; Eight Grade-IIIB tibial fractures that were associated with large soft-tissue and segmental diaphyseal defects, averaging ten centimeters in length, were successfully reconstructed without the use of a free fibular transfer . A free tissue flap was the preferred form of soft-tissue coverage . The osseous reconstruction was accomplished by using a massive amount of autogenous cancellous bone graft . Beads that were made from polymethylmethacrylate and impregnated with two antibiotics at the time of operation were used as soft-tissue spacers to preserve the volume of the diaphyseal defect for later receipt of the cancellous bone graft . The beads prevented the soft-tissue flap from collapsing into and adhering to the site of the tibial defect . The beads also served as vehicles for local delivery of the antibiotics that they contained . When the soft-tissue flap had healed, the beads were replaced with cancellous graft . All of the tibiae healed . The time to healing averaged nine months . The average duration of external fixation was 5.5 months . One deep infection developed, but resolved after debridement and antibiotic therapy . This conservative technique is safe and reliable for patients who have sustained a high-energy tibial fracture and a large segmental diaphyseal defect. Transplantation, 1989 Aug, 48(2), 266 - 71 Biopsy diagnosis and clinical outcome of persistent focal pulmonary lesions after marrow transplantation; Crawford SW et al.; We reviewed the results of all percutaneous fine needle aspirations (FNA) and open lung biopsies (OLB) after bone marrow transplantation at our center (1984-1987) for the evaluation of focal lung lesions that developed or persisted despite antibiotic administration . We sought to determine the prevalence and types of infections, the yield of diagnostic procedures, and the clinical outcome of these focal lesions . Infection was documented in 78% (18/23) of all lesions and was fungal in each case . FNA detected fungal lung infection with a sensitivity of 67% (10/15) but had a negative predictive value of only 50% (5/10) . Complications occurred in 15% of FNA . OLB without prior FNA was performed in 6 cases and demonstrated fungal infections in 5 . Overall, seven of the 18 patients with localized invasive fungal lung disease recovered after antifungal therapy . This study demonstrates that focal lung lesions that develop or persist despite antibiotics after BMT are most often fungal . FNA may safely identify these localized infections in selected patients and with appropriate treatment recovery may be achieved. Emerg Med Clin North Am, 1989 Aug, 7(3), 667 - 82 Toxicologic causes of acute abdominal disorders; Mueller PD et al.; A variety of drugs and toxins can produce severe abdominal pain and, in some cases, a surgical abdomen . Toxins can be classified according to mechanisms of injury: 1 . Corrosives often produce severe gastroenteritis and may result in gastric or esophageal perforations . Examples of corrosive substances include aspirin, iron, mercury, acids and alkali . 2 . Drugs may cause intestinal ileus or obstruction by pharmacologic actions (i.e., anticholinergic drugs and narcotics) or by mechanical obstruction (charcoal and drug bezoars) . 3 . Abdominal pain simulating an acute abdomen may result from systemic effects of black widow spider envenomation or intoxication with heavy metals such as lead and arsenic . 4 . Ischemic bowel disease may occur from use of vasoconstrictor drugs, such as ergotamines, amphetamines and cocaine, or may follow treatment with catecholamines or digitalis in critically ill patients . Small bowel ischemia is life-threatening and may require bowel resection . 5 . Many drugs cause abdominal pain by directly injuring abdominal organs, such as the liver and pancreas . Antibiotic-associated colitis may present with abdominal pain and inflammatory diarrhea . Consideration of drugs and toxins plays an important role in the differential diagnosis of the acute abdomen. Fiziol Zh SSSR Im I M Sechenova, 1989 Aug, 75(8), 1095 - 101 {The effect of neomycin on the contractile activity of the skeletal muscles in the frog}; Danilenko MP et al.; Neomycin, a selective inhibitor of the phosphoinositide metabolism, depending on its concentration and the incubation time, depressed the K+-contractures and contractions of m . sartorius R . ridibunda caused by a single or a tetanic electrostimulation . In the experiments on m . rectus abdominis, neomycin inhibited the Ach- and oubaine contractures but not the K+ ones . The contractures of both muscles induced with caffeine did not change in presence of the above antibiotic . The data obtained suggest a participation of phosphoinositides contractions of skeletal muscles induced by excitation of the plasma membrane. Antibiot Khimioter, 1989 Aug, 34(8), 620 - 4 {Pharmacokinetics of azlocillin in critical conditions: an individualized schedule of drug administration in relation to anatomo-physiologic and pathologic factors}; Firsov AA et al.; Azlocillin pharmacokinetics was studied after a single intravenous injection of the antibiotic in a dose of 4 g in 20 patients in critical state . To elucidate the causes of significant individual variability of the antibiotic pharmacokinetics observed in the patients, multiple correlation analysis of the main pharmacokinetic parameters i . e . the area under the concentration/time curve, total clearance, steady-state volume of distribution and mean residence time was performed in regard to the "patient factors" such as sex, age, the volumes of transfused liquid, blood, plasma and blood substitutes, hemoglobin levels, erythrocyte count and ESR . Adequate correspondence of the predicted by the "patient factor" values of the areas under the concentration/time curve and the total clearance to the actually determined values was observed . Correspondence of the predicted values to the steady-state volume of distribution and the mean residence time to the actually determined values was satisfactory . A procedure for design of azlocillin individual dosage regimens based on calculating individual clearance by the "patient factors" is described. Surg Neurol, 1989 Aug, 32(2), 105 - 10 Craniotomy improves outcome in subdural empyema; Feuerman T et al.; Renewed uncertainty regarding the best technique of surgical therapy (burr holes versus craniotomy) for subdural empyema prompted a review of the experience with this disease entity at UCLA . Based on data obtained from this review and from studies previously published in the literature, the keys to optimal outcome are rapid diagnosis, craniotomy with total removal of pus, and appropriate antibiotic therapy . The clinical syndrome of subdural empyema can overlap that of other intracranial infections; infants and young children present with a different syndrome than older children and adults . Computed tomography scanning is nearly always diagnostic but may be equivocal or normal; magnetic resonance imaging may become the diagnostic study of choice . Multiple organisms are often cultured, which requires multiple drug therapy. Antimicrob Agents Chemother, 1989 Aug, 33(8), 1393 - 4 In vitro studies of Chlamydia trachomatis susceptibility and resistance to rifampin and rifabutin; Treharne JD et al.; Although rapid emergence of antibiotic-resistant mutants of Chlamydia trachomatis occurs when the organism is grown in subinhibitory concentrations of rifampin, no such mutants could be demonstrated when the organism was propagated under the same conditions in subinhibitory levels of the related drug rifabutin. J Gen Virol, 1989 Aug, 70 ( Pt 8), 2171 - 7 Retention and expression of the left end subfragment of the herpes simplex virus type 2 BglII N DNA fragment do not correlate with tumorigenic conversion of NIH 3T3 cells; Kessous-Elbaz A et al.; Cotransfection experiments have been carried out using recombinant plasmids pAG60, conferring resistance to antibiotic G418, and pXho3 which contains the left end subfragment (map coordinates 0.583 to 0.596) of the transforming herpes simplex virus type 2 BglII N DNA fragment and encodes the 36K polypeptide associated with the viral ribonucleotide reductase activity . Several NIH 3T3 cell clones resistant to G418 and having morphological changes commonly observed for transformed NIH 3T3 cells were isolated and examined for the presence and stable retention of the viral sequences . Seven of the clones that retained the transfected viral sequences were analysed for the expression of the 36K polypeptide and the tumorigenic phenotype . The results gathered from these studies show that neither the retention of the viral DNA nor the expression of the 36K polypeptide correlated with tumorigenic conversion of these cells. Cardiovasc Res, 1989 Aug, 23(8), 709 - 14 Uneven host tissue ongrowth and tissue detachment in stent mounted heart valve allografts and xenografts; Maxwell L et al.; Following explanation from the mitral position because of primary tissue failure, 30 human antibiotic sterilised stent mounted aortic valve allografts and 28 glutaraldehyde treated porcine xenografts were examined for evidence of tissue detachment from the stents . These grafts had been in situ for 34 to 166 months . Graft detachment had occurred from one or two stent posts with displacement of the commissures and central valvular incompetence in 12 (67%) of 18 allografts supported on rigid stainless steel stents, in six (50%) of 12 allografts mounted on flexible acetal copolymer stents, but in only one (4%) of 28 xenografts mounted on polypropylene stents . In regions of detachment the aortic remnant of the graft was infiltrated by components of blood and phagocytic cells which had removed not only fibrin but also graft tissue . Detachment did not occur from stent posts where the graft margin had become coated by collagenous host tissue . This intimal fibrous sheath appeared not only to strengthen the attachment of the graft but also to limit the entry of fibrin and phagocytes into the graft tissue. Contact Dermatitis, 1989 Aug, 21(2), 79 - 82 Erythroderma due to ribostamycin; Puig LL et al.; A 48-year-old man became erythrodermatous after intramuscular administration of ribostamycin, an aminoglycoside antibiotic in the same family as neomycin . Patch tests were positive to ribostamycin and neomycin, as well as to mercurials . There was no mercurial preservative in the injection solution . A lymphocyte transformation test was positive for ribostamycin and tobramycin, but not for gentamycin . Diagnostic and structure-activity relationship aspects of the case are discussed. Endod Dent Traumatol, 1989 Aug, 5(4), 188 - 92 Effects of combining Ledermix and calcium hydroxide pastes on the diffusion of corticosteroid and tetracycline through human tooth roots in vitro; Abbott PV et al.; A 50:50 mixture of a corticosteroid/antibiotic paste and calcium hydroxide has been used clinically as a root canal dressing agent . This study investigated the effect on the release and diffusion of the corticosteroid and antibiotic components of Ledermix paste when it was mixed with a calcium hydroxide-methyl cellulose paste . The release rates of the trace molecules were lower when the mixture was used compared with release from Ledermix alone . The results indicated that this combination of materials, when used a long-term intracanal dressing, was likely to be more effective than Ledermix alone. Enferm Infecc Microbiol Clin, 1989 Aug-Sep, 7(7), 364 - 7 {Neutropenia secondary to cefotaxime use}; Burgaleta C et al.; Agranulocytosis is an uncommon complication of beta-lactam antibiotic therapy . Two patients who developed absolute neutropenia and anemia after having received 168 g of cefotaxime are reported . There was fever and rash, and hematologic recovery too place 10 and 6 days after withdrawal of the drug . The bone marrow culture showed that the incubation of cells with cefotaxime (10 micrograms/ml) induced a 26 +/- 1% inhibition of the formation of granulocytic colonies (CFU-GM) in controls and a 47% and 48% inhibition, respectively, in the two patients with neutropenia . When serum was added to the culture, the control serum improved the in vitro granulopoietic response, while the serum from the first patient inhibited in 77 +/- 1.5% the formation of CFU-CM in the control marrow . The need for the monitoring of peripheral blood cells in patients receiving long term treatment with beta-lactam antibiotics emphasized, as we have shown the suppressor effect of cefotaxime on the hematopoietic precursors and the effect of an autoimmune mechanism in some cases. Ophthalmology, 1989 Aug, 96(8), 1194 - 7 Bilateral keratitis in Lyme disease; Kornmehl EW et al.; Lyme disease, caused by the spirochete Borrelia burgdorferi, has ophthalmic manifestations . The authors describe two cases of Lyme keratitis characterized by multiple focal, nebular opacities at varying levels of the stroma which may progress to edema, neovascularization, and scarring . Close observation, in addition to systemic antibiotic therapy, may be sufficient if the visual axis is not involved, and the patient is asymptomatic. J Chromatogr, 1989 Jul 28, 475, 353 - 61 Isolation of drug residues from tissues by solid phase dispersion; Barker SA et al.; A new method based on solid phase dispersion of tissue for the subsequent isolation of drugs is reported . By blending tissues with a polymeric phase bound to a solid support one obtains a semi-dry material which can be used as a column packing material from which one can isolate drugs in a stepwise fashion based on the solubility characteristics of the drugs in this matrix . The applicability of this approach for multidrug residue extraction from a single sample is demonstrated for compounds representing the organophosphate, benzimidazole anthelmintic and beta-lactam antibiotic drug classes. Biochim Biophys Acta, 1989 Jul 24, 983(1), 15 - 22 Duramycin effects on the structure and function of heart mitochondria . I . Structural alterations and changes in membrane permeability; Sokolove PM et al.; The polypeptide antibiotic duramycin has been reported to interact specifically with two lipids: phosphatidylethanolamine (PE) and monogalactosyldiacylglycerol (Navarro et al . (1985) Biochemistry 24, 4645-4650) . PE is a major component of mitochondrial membranes . Duramycin was used to examine the role of PE in maintenance of mitochondrial structure and membrane permeability properties with the following results: (1) Duramycin addition to isolated rat heart mitochondria produced abrupt organelle contraction which was followed, depending on composition of the suspending medium, by pronounced swelling . The most notable morphological effect of the antibiotic was ruffling or crenelation of the outer membrane, which resulted ultimately in its separation from the inner membrane . (2) Low concentrations (less than 5 microM) of the antibiotic selectively increased the permeability of the mitochondrial inner membrane to cations and small solutes . This effect was blocked by atractyloside, a highly specific inhibitor of the adenine nucleotide translocator, by palmitoyl coenzyme A, by N-ethylmaleimide, and by AMP, ADP and ATP but not GDP or GTP, implicating the adenine nucleotide translocator in the selective permeability increase . (3) Higher concentrations of duramycin induced a more generalized permeability increase which was not subject to inhibition by compounds capable of interacting with the adenine nucleotide translocator. FEBS Lett, 1989 Jul 17, 251(1-2), 167 - 72 'Perforated patch recording' allows long-term monitoring of metabolite-induced electrical activity and voltage-dependent Ca2+ currents in pancreatic islet B cells; Falke LC et al.; We describe the application of 'perforated patch recording' using the pore-forming antibiotic nystatin, to monitor the electrical activity and underlying ionic currents of rat and human pancreatic islet B cells . We demonstrate that glucose-induced electrical activity is seen even in single B cells during current-clamp recordings lasting hours 'L-type' Ca2+-channel currents can also be monitored over this period of time . This technique may prove useful in examining hormone and neurotransmitter modulation of electrical activity in B cells, while minimizing the effects of cytoplasmic 'wash-out'. Cancer Lett, 1989 Jul 15, 46(2), 153 - 7 Potentiation of cisplatin antitumor activity on L1210 leukemia s.c . by sparsomycin and three of its analogues; Zylicz Z et al.; Sparsomycin (Sm) is a known antibiotic derived from Streptomyces . Its potential antitumor activity stimulated the search for a synthetic production method and the development of new derivatives . In a recent screening investigation, three Sm analogues appeared to be more active and considerably less toxic than the parent drug . Sparsomycins became especially interesting when it was shown that Sm potentiates the antitumor activity of cisplatin . In the present study Sm and its three promising analogues: deshydroxy-Sm (dSm), ethyl-deshydroxy-Sm (EdSm) and n-pentyl-Sm (PSm) were studied for their cisplatin potentiating effect . The experiments were performed on CD2F1 mice inoculated with 10(6) L1210 cells s.c . Sparsomycins were administered i.p . 3 h before cisplatin on days 1, 5 and 9 . Three of the drugs, Sm, dSm and PSm, showed no potentiating effect in this tumor model . At a dose of 10 mg/kg, EdSm potentiated cisplatin antitumor activity 2.8 times (P less than 0.01) without an increase in weight loss . These results warrant further investigation. Biochem J, 1989 Jul 15, 261(2), 445 - 50 Polymyxin B diminishes blood flow to brown adipose tissue and lactating mammary gland in the rat . Possible mechanism of its action to decrease the stimulation of lipogenesis on refeeding; Tedstone AE et al.; Polymyxin B, a cyclic decapeptide antibiotic, increased blood glucose and lactate, and inhibited the stimulation of lipogenesis in interscapular brown adipose tissue and lactating mammary gland of starved-refed virgin and lactating rats respectively . Lipogenesis was not inhibited in white adipose tissue or liver . The antibiotic increased the haematocrit . The relative blood flow to brown adipose tissue and lactating mammary gland was decreased by polymyxin B, and this was accompanied by a decrease in tissue ATP content . In vitro polymyxin B did not affect glucose utilization or conversion into lipid, nor the stimulation by insulin of these processes in brown-adipose-tissue slices . Treatment of rats in vivo with polymyxin B resulted in decreased utilization of glucose in vitro in brown-adipose-tissue slices . Similarly, acini from mammary glands of polymyxin B-treated lactating rats had decreased rates of conversion of {1-14C}glucose to lipid . It is concluded that the effects of polymyxin B may be brought about by decreases in tissue blood flow . The possibility that these effects are secondary to inhibition of glucose utilization cannot be ruled out. Hosp Pract (Off Ed), 1989 Jul 15, 24(7), 93 - 100, 103-4, 107-10 Combating infections in neutropenic patients; Pizzo PA; In febrile neutropenic patients, most of whom have cancer, immediate, albeit empiric, antibiotic therapy reduces infectious morbidity and mortality . With respect to definitive therapy, it is stressed that isolate patterns are changing, even as new antibiotics are becoming available . Issues such as single-agent versus combination therapy, as well as preventive strategies, are reviewed. Biochim Biophys Acta, 1989 Jul 10, 982(2), 245 - 52 Interaction of amphotericin B and its N-fructosyl derivative with murine thymocytes: a comparative study using fluorescent membrane probes; Henry-Toulme N et al.; The polyene antibiotics amphotericin B (AmB) and N-(1-deoxy-D-fructos-1-yl)amphotericin (N-Fru-AmB) have different activity towards murine thymocytes (N-Fru-AmB is less toxic but is a potent immunomodulator) . The interactions of the drugs with these cells have been studied by fluorescence methods . Fluorescence energy transfer from 1-{4-(trimethylammonio) phenyl}-6-phenylhexa-1,3,5-triene, p-toluenesulfonate (TMA-DPH) to polyenes was used to follow the binding of the two drugs to the plasma membrane . The results, confirmed by circular dichroism measurements, indicate that at saturation the ratio AmB bound/plasma membrane lipid is low (less than 1 molecule of polyene for 170 lipids) . The slightly higher binding of AmB as compared to N-Fru-AmB demonstrates that affinity of the antibiotic for plasma membrane does not account for the activity of the polyenes towards lymphocytes . The effect of the two polyenes on membrane fluidity was studied by steady-state fluorescence anisotropy . The results suggest that AmB strongly perturbs the structure of the membrane whereas only a slight decrease of the anisotropy is observed with N-Fru-AmB in the range of concentration where the biological activity has been demonstrated . Polyene location was further investigated by comparing the energy transfer efficiency obtained with TMA-DPH and with the parental compound 1,6-diphenylhexa-1,3,5-triene, p-toluene sulfonate (DPH) . While AmB binds to plasma membrane, as well as to intracellular structures, N-Fru-AmB seems to accumulate into the cell and bind to intracellular membrane structures. Biochim Biophys Acta, 1989 Jul 7, 1008(2), 234 - 42 Inhibition of rat growth hormone promoter activity by site-specific DNA methylation; Gaido ML et al.; The effect of methylation on rat growth hormone (rGH) promoter activity was determined in GH3 cells by measuring rGH-Neo and rGH-CAT fusion gene expression with or without prior in vitro treatment with the site-specific DNA methyltransferases, M-BsuE and M-HhaI . To assay for rGH-promoter-specific effects of DNA methylation, RSV-Neo and RSV-CAT activities with or without M-BsuE, M-HhaI and M-HpaII treatment were measured in parallel cultures of GH3 cells . GH1-Neo and RSV-Neo fusion gene expression was inhibited by in vitro methylation from 44 to 83% as measured by the number of Geneticin-resistant GH3 cell colonies . Methylation of the GH1 promoter by M-BsuE exhibited some selective inhibition of Neo expression as determined by colony numbers, although extensive methylation of non-promoter DNA in GH1-Neo and RSV-Neo by M-HhaI and M-HpaII also inhibited Neo expression . Southern blot analysis of genomic DNA isolated from the Geneticin-resistant GH3 cells indicated that Geneticin-resistance was accompanied by demethylation of the BsuE (ThaI) sites in stably incorporated GH1-Neo DNA but not RSV-Neo DNA . Transient expression of the CAT gene in GH3 cells was selectively inhibited by 60% upon methylation of two BsuE (ThaI) sites in the GH1 promoter of GH1-CAT by M-BsuE . The data demonstrate, for the first time, to our knowledge, a direct effect of DNA methylation on the activity of the rat growth hormone promoter. FEBS Lett, 1989 Jul 3, 250(2), 323 - 7 Sequence selective binding of ditrisarubicin B to DNA: comparison with daunomycin; Fox KR et al.; DNase I footprinting has been used to examine the sequence selective binding of ditrisarubicin B, a novel anthracycline antibiotic, to DNA . At 37 degrees C no footprinting pattern is observed, the drug protects all sites from enzymic cleavage with equal efficiency . At 4 degrees C a footprinting pattern is induced with low drug concentrations which is different from that produced by daunomycin . The best binding sites contain the dinucleotide step GpT (ApC) and are located in regions of alternating purines and pyrimidines. Z Orthop Ihre Grenzgeb, 1989 Jul-Aug, 127(4), 471 - 3 {5 years' infection statistics of an orthopedic clinic--pathogen spectrum, resistance status, therapeutic consequences}; Braun M; In 1983 we started our statistical control for postoperative infections . The data are checked every half year . Most common bacteria was Staph . aureus followed by Staph . epidermidis . We found a difference in the spectrum of bacteria between our postop . patients and the referred cases . A surgeon related control and our new operating theatres reduced the infection rate from 2.2% to 0.8% . For our total joint replacements we additionally used perioperative antibiotics . The change in the antibiotic from Cefoxitine to Cefacedone reduced the infection rate from 4.7% to 0.8% . The permanent control of bacteria and of their resistance to antibiotics allows us to reduce the number of drugs used and to simplify treatment without loosing efficiency of therapy . This is--in a double sense--a good way for reducing costs. Jpn J Antibiot, 1989 Jul, 42(7), 1477 - 87 {Clinical studies of cefpodoxime proxetil in pediatric field}; Kimura S et al.; Clinical studies of cefpodoxime proxetil (CPDX-PR), a new cephem antibiotic, were carried out in 60 patients in the pediatric field . The overall efficacy rate on 54 patients with various infections was 98.1%, and few side effects, all of them very mild, were developed in 6 of 60 patients (10%) . It was concluded that CPDX-PR was one of the most useful antibiotics in the pediatric field because of the high efficacy rate and the safety. J Antimicrob Chemother, 1989 Jul, 24(1), 45 - 51 Gentamicin and low dose piperacillin in febrile neutropenic patients; Boughton BJ et al.; One hundred and twenty-seven febrile neutropenic patients were randomized to receive empirical antibiotic therapy with intravenous gentamicin and 12 g/day or 8 g/day piperacillin . Despite a high incidence of Hickman catheter infections by antibiotic-resistant bacteria, there was an overall response in 56% of patients and no difference in the numbers responding to each antibiotic regimen . In addition, the duration of fever was not significantly different in the two groups of patients . The majority of the unresponsive patients responded to the addition of further antibiotics and there were only two infection related deaths . The results suggest that high dose antibiotics are not essential for the initial empirical therapy in febrile neutropenic patients. J Clin Immunol, 1989 Jul, 9(4), 279 - 86 Immunoglobulin levels in saliva in individuals with selective IgA deficiency: compensatory IgM secretion and its correlation with HLA and susceptibility to infections; Norhagen G et al.; Total levels of IgA, IgM, and IgG were measured in unstimulated whole saliva and serum from 63 individuals with selective IgA deficiency . Values were compared with the incidence of upper respiratory tract infections, antibiotic treatments (necessitated by upper respiratory tract infection), and HLA antigens . A statistically significant increase in salivary IgM and IgG levels was noted in individuals with selective IgA deficiency compared to healthy normal individuals . Healthy individuals with selective IgA deficiency did not have increased concentrations of salivary IgM compared to infectious-prone patients . Nor was there any correlation found between proneness to infections and HLA antigens or between salivary IgM or IgG levels and HLA antigens in this patient material. Infection, 1989 Jul-Aug, 17(4), 245 - 6 Influence of milk on the bioavailability of doxycycline--new aspects; Meyer FP et al.; This study was conducted to examine the pharmacokinetics of doxycycline in nine healthy volunteers who had fasted overnight . Single-dose cross-over design was used . Each subject received orally 0.2 g doxycycline . The subjects swallowed the antibiotic capsules with 300 ml of water or 300 ml of fresh milk . Simultaneous ingestion of milk diminished the peak plasma concentration by 24% and the absorption by 9-53% (mean 30%) . It is concluded that, like the other tetracyclines, doxycycline should not be administered together with milk. Fundam Appl Toxicol, 1989 Jul, 13(1), 146 - 55 Differential effects of cefmetazole sodium on the reproductive system of infant and pubertal male rats; Moe JB et al.; The effects of cefmetazole (CMZ), a cephem antibiotic which contains the N-methyltetrazolethiol (NMTT) side-chain moiety, were compared in infant (6-42 days of age) and pubertal (6-10 weeks of age) male Sprague-Dawley rats . High doses of either CMZ or free NMTT caused reductions in testicular weight and delayed maturation of spermatogenic germ cells in the testes of infant rats, implicating NMTT as the active component in causing these effects . Pubertal rats expressed neither of these effects, even when treated with doses of CMZ far in excess of those used in infant rats . The effects of CMZ and NMTT on testicular weights and histologic features of testes of rats treated as infants were mainly reversed when these animals were examined 35 and 70 days after cessation of treatment . All reproductive functional parameters were normal in mating studies using male rats which had been treated with CMZ or NMTT as infants and allowed to recover . Because of the species differences in rates of sexual maturation and the greater rate at which rats metabolize CMZ to NMTT, the relevance to humans of the testicular effects of CMZ in infant rats is unknown. Eur J Haematol, 1989 Jul, 43(1), 15 - 21 Prognostic significance of peripheral blood S + G2/M phase size in adult acute non-lymphoblastic leukaemia; Guerci A et al.; Flow cytometric analysis of peripheral blood (PB) S + G2/M phase size was performed in 73 adult patients with untreated acute non-lymphoblastic leukaemia, to assess whether the results may correlate to response rate and patient prognosis . All patients were treated with the same induction chemotherapy regimen: ARA-C alone or in combination with an anthracycline antibiotic . Pretreatment PB S + G2/M phase size is significantly correlated to induction response rate (p less than 0.02), duration of response (p less than 0.02) and duration of survival . Patients with low PB S + G2/M phase size experience a longer survival, in patients over and below 50 yr (p less than 0.001) . Lastly, early deaths tend to be more frequent in the high median age and high PB S + G2/M phase size group . Our study suggests that PB S + G2/M phase size has prognostic significance in obtaining response and duration of survival. Br J Ophthalmol, 1989 Jul, 73(7), 576 - 8 Eyelid swelling and erythema as the only signs of subperiosteal abscess; Rubin SE et al.; On clinical grounds it is usually easy to distinguish between preseptal cellulitis, a cutaneous infection not threatening to vision, and orbital cellulitis, a potentially vision threatening infection of the orbital tissues generally arising from paranasal sinusitis . We recently cared for two patients with a clinical diagnosis of preseptal cellulitis who had CT scan evidence of subperiosteal abscess . Antibiotic therapy alone resulted in clinical resolution in each case. J Antibiot (Tokyo), 1989 Jul, 42(7), 1088 - 99 Selection of a specifically blocked mutant of Streptomyces cinnamonensis: isolation and synthesis of 26-deoxymonensin A; Ashworth DM et al.; Streptomyces cinnamonensis produces the polyether ionophore antibiotic monensin A . Following a single round of mutagenesis by UV light, a derivative of this strain has been isolated, which secretes a new metabolite identified as 26-deoxymonensin A (3) . The structural elucidation of the new metabolite followed from a spectroscopic analysis, and its identity was proven conclusively following a comparison to 26-deoxymonensin A (3) obtained synthetically from monensin A . The preparation of labelled forms of 3 is described, together with incorporation experiments using the parent strain of S . cinnamonensis . Only very low levels of incorporation of 3 into monensin A were observed. J Comput Assist Tomogr, 1989 Jul-Aug, 13(4), 656 - 8 Septic thrombosis of the portal vein: CT and clinical observations; Lim GM et al.; The CT and clinical findings were reviewed in seven patients with septic thrombosis of the portal vein (STPV) . Of the seven patients, five had associated pyogenic liver abscesses . Five of seven patients presented de novo with STPV without a clinically obvious extrahepatic source of intraabdominal infection . All seven patients were successfully managed nonsurgically with intravenous antibiotics and in two patients percutaneous drainage of hepatic abscesses . Serial follow-up examinations in five patients demonstrated complete resolution of portal venous thrombus in three patients and progression to cavernous transformation in two . When diagnosed early by CT or sonography, STVP may have a more benign clinical course following appropriate antibiotic therapy. J Cell Biol, 1989 Jul, 109(1), 285 - 93 Induction of in vitro differentiation of mouse embryonal carcinoma (F9) and erythroleukemia (MEL) cells by herbimycin A, an inhibitor of protein phosphorylation; Kondo K et al.; Herbimycin A is one of the benzenoid ansamycin antibiotics isolated from a culture of Streptomyces species (Omura, S., A . Nakagawa, and N . Sadakane . 1979 . Tetrahedron Lett . 1979: 4323-4326) . Recent studies have shown that the antibiotic not only inhibits the phosphorylation of p60src in Rous sarcoma virus- (RSV) infected cells, but also reverses the cellular phenotypes acquired by transfection with tyrosine kinase oncogenes (Uehara, Y., M . Hori, T . Takeuchi, and H . Umezawa . 1985 . Jpn . J . Cancer Res . 76:672-675; Uehara, Y., M . Hori, T . Takeuchi, and H . Umezawa . 1986 . Mol . Cell . Biol . 6: 2198-2206; Uehara, Y., Y . Murakami, S . Mizuno, and S . Kawai . 1988 . Virology . 164: 294-298) . These studies and other evidence indicate that the antibiotic inhibits a reaction(s) closely associated with the function of cellular tyrosine kinases . We have found that herbimycin A is an effective inducing agent capable of triggering differentiation in two typical mouse in vitro differentiation systems, which have been considered to be quite different in their mechanism of induction: endoderm differentiation of embryonal carcinoma (F9) cells and terminal erythroid differentiation of erythroleukemia (MEL) cells . The results suggest that there is a common step in the intracellular differentiation cascade which is, directly or indirectly, associated with phosphorylation at specific (tyrosine) residues of cellular proteins . The significance of this finding with respect to the molecular mechanism of in vitro differentiation is discussed. Postgrad Med, 1989 Jul, 86(1), 79 - 81, 84, 89 Pyomyositis in patients with diabetes . Computed tomography as a key to diagnosis; Brown RL; Pyomyositis rarely occurred in nontropical climates in the past but is becoming increasingly recognized in temperate climates . Nevertheless, this diagnostic possibility is often not immediately recognized . Pyomyositis should be considered in diabetic patients with lower-extremity cellulitis who do not respond to presumptively appropriate therapy . A high index of suspicion and documentation with appropriate imaging techniques, aggressive surgical intervention, and adjunctive antibiotic therapy are the keys to prompt resolution without sequelae . The patients in this report were diabetic adults who responded to appropriate therapy after computed tomographic scans, surgical exploration, and cultures established the diagnosis. J Thorac Cardiovasc Surg, 1989 Jul, 98(1), 48 - 55; discussion 55-6 Durability of the viable aortic allograft; Angell WW et al.; Of 581 aortic allografts implanted since 1967, 421 were analyzed for structural deterioration . This series is unique in that it includes patients from the early allograft experience . All allografts were cleanly procured, antibiotic sterilized, and either stored at 4 degrees C for up to 8 weeks or frozen to liquid nitrogen temperatures with cryopreservation to preserve the viable cusp fibroblasts . There were 25 frozen mounted aortic valves with a median time to valve failure of 12.1 years, which was not significantly different from the 12.5-year period for 114 fresh free-sewn aortic valves . The median time to valve failure was 6.6 years for 90 fresh-mounted aortic valves and 8.6 years for 192 fresh-mounted mitral valves (p = 0.05) . The difference between all mounted and unmounted grafts was significant (p = 0.0001) . In all groups, viable fibroblasts were present in specimens explanted up to 5 years after the operation . All specimens returned after more than 10 years were almost totally acellular . Evidence of increased collagen, suggesting that the fibroblasts survive implantation and then gradually die, was present in all specimens . This series suggests that durability of the unmounted viable allograft for aortic valve replacement is greater than for other types of tissue valves . Pre-mounted allografts for aortic or mitral valve replacement have a median survival of 8 years and are not more durable than other tissue valves. Am J Emerg Med, 1989 Jul, 7(4), 413 - 6 Emergency presentation of coalescent mastoiditis; Rogers SM et al.; Since the introduction of sulfonamides in the late 1930s, coalescent mastoiditis is an uncommon complication of otitis media . Swelling, erythema, and tenderness over the mastoid area with associated anterior displacement of the auricle are classic signs and symptoms of coalescent mastoiditis with formation of a subperiosteal abscess . Early recognition of this entity is essential to prevent its complications . Prompt otolaryngologic consultation is indicated and inpatient antibiotic therapy should be begun . Surgical treatment is also needed and may obviate further complications. J Assoc Physicians India, 1989 Jul, 37(7), 469 - 70 Fatal pancytopenia in falciparum malaria; Arya TV et al.; Various pernicious syndromes in Plasmodium falciparum infection are being reported with increasing frequency from tropical countries . A rare case of fatal pancytopenia associated with falciparum malaria is described . The patient developed fulminant aspiration bronchopneumonia which was unresponsive to antibiotic therapy and contributed to the development of adult respiratory distress syndrome . He also had severe uncontrolled gastrointestinal bleeding and possibly an intracerebral haemorrhage . Anaemia and thrombocytopenia are well known in malaria but severe leucopenia is very rare and pancytopenia has not been reported. Mol Endocrinol, 1989 Jul, 3(7), 1090 - 8 Transforming growth factor beta 1: importance of glycosylation and acidic proteases for processing and secretion; Sha X et al.; The role of glycosylation of the transforming growth factor-beta 1 (TGF-beta 1) precursor was investigated by treating a transfected Chinese hamster ovary (CHO) cell line expressing high levels of recombinant TGF-beta 1 (TGF-beta 3-2000 cells) with a series of glycosylational inhibitors . Tunicamycin, a nucleoside antibiotic which prevents the formation of the dolichol intermediate necessary for oligosaccharide addition of the nascent polypeptide chain, appeared to block secretory exit and led to an increase in the cellular associated, nonglycosylated pro-TGF-beta 1 form . 1-Deoxymannojirimycin and swainsonine, inhibitors of the mannosidases I and II, respectively, blocked complete glycoprotein processing of the TGF-beta 1 precursor as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by sensitivity to glycosidases . However, the abnormal TGF-beta 1 polypeptides containing the altered carbohydrate side chains were secreted readily by the CHO cells . In contrast, inhibitors of the glucosidases at the first step in glycoprotein remodeling, 1-deoxynojirimycin and castanospermine, markedly inhibited secretion of the TGF-beta 1 polypeptides from transfected CHO cells . In all cases, these inhibitors did not appear to affect proteolytic processing of the TGF-beta 1 polypeptides . Furthermore, inhibitor treatment did not affect mannose-6-phosphorylation of the TGF-beta 1 polypeptides . These results suggest that glycosylation and early stage remodeling of oligosaccharide side chains are necessary for secretion of TGF-beta 1 . Treatment of the transfected CHO cells with weak bases (NH4Cl and chloroquine), or a monovalent ionophore (monensin), prevented proteolytic processing of the TGF-beta 1 precursor indicating that cleavage occurs by proteases in an acidic cellular compartment. Chirurg, 1989 Jul, 60(7), 479 - 8 {Extra-anatomic bypass as therapy of infected bacterial (mycotic) infrarenal aortic aneurysm . A comparative, literature supported analysis}; Belz J et al.; Based on a review of the literature we compared the results of various operative procedures for infrarenal bacterial infected (mycotic) aortic aneurysms . We conclude that the preferred therapy involves the placement of an extraanatomic bypass, resection of the aneurysm and thorough debridement of infected tissue . Obligatory is appropriate systemic antibiotic therapy . The mortality rate has been substantially reduced since the introduction of this therapeutic concept. Occup Med, 1989 Jul-Sep, 4(3), 463 - 71 Hand infections seen in the industrial clinic; Kasdan ML et al.; Following a few basic principles will help the industrial physician in managing hand infections . They are: (1) recognizing the infection early; (2) drainage and/or debridement; (3) identifying the organism; and (4) antibiotics . Following the course of a wound is extremely important . The infected wound that does not respond to surgery and antibiotics may need to be re-explored and cultured again . The wound that heals well without antibiotics or on the wrong