Antibiotics

J Med Assoc Thai, 1983 Mar, 66(3), 176 - 82
Midtrimester abortion by hypertonic saline instillation experience in Ramathibodi Hospital; Suthutvoravut S et al.; PIP: A retrospective study of midtrimester abortions using the intraamniotic instillation of hypertonic saline solution was conducted . All 62 cases admitted to the Ramathibodi Hospital in Bangkok, Thailand for midtrimester abortion in 1980 were terminated by intraamniotic hypertonic saline instillation . The pregnancies were unwanted in 32 (51.6%) of the cases because of family problems, poor socioeconomic status, and deteriorated psychological health . 15 cases (24.2%) were preganancy from rape; 9 (14.5%) had rubella infection during the 1st trimester; and 3 cases (4.8%) were mentally retarded . There was 1 case of renal staghorn calculi post nephrostomy, 1 of multiparity with history of hemophilia in the family, and 1 of failed IUD contraception . The women were between 16-25 years of age in 39 cases, aged 15 or under in 4 cases (6.5%), and over age 35 in 4 cases . In 49 cases (79%) abortion was performed during 16-20 weeks gestation, in 12 cases (19.1%) at 21-24 weeks, and in 1 case at 25 weeks of gestation . The time interval from hypertonic saline instillation to abortion was analyzed in order to evaluate the effect of parity, amount of amniotic fluid withdrawn, and oxytocin augmentation . The mean instillation to abortion time (I-A) was 30.19 +or- 11.25 hours . There were 3 cases which did not receive oxytocin and who spontaneously aborted within 24 hours . Among cases which received oxytocin augmentation, there were 9 who received oxytocin immediately after instillation and 50 who received it 18-24 hours later . The I-A time was 31.22 +or- 11.63 hours in the group that received oxytocin immediately and 31.09 +or- 10.68 in the group receiving it later . There was no statistical difference between the 2 groups . Among the 50 cases which received oxytocin augmentation 18-24 hours later, there was no statistical difference between groups of nulliparity and multiparity . There were 46 cases in which the amount of amniotic fluid withdrawn was noted . In the group in which more than 200 ml of amniotic fluid was withdrawn, the I-A time was 26.81 +or- 7.28 hours . In comparison to the group in which less than 50 ml of amniotic fluid was withdrawn, the I-A time was 28.88 +or- 16.24 hours . There was no statistical difference between the 2 groups . The longer I-A times were found in groups in which 51-1000 ml and 151-200 ml of amniotic fluid were withdrawn . The most common complication was retained placenta (8 cases) . There was only 1 case of hemorrhage . There were 2 cases of fever and 1 case of nausea and vomiting . On follow-up of 46.8% of the cases, 2 cases of cervicitis and 3 cases of vaginitis were found and treated with antibiotic suppositories .

Ontogenez, 1983 Mar-Apr, 14(2), 162 - 5
{Sensitivity of the hematopoietic stem cells of anemic animals to actinomycin D}; Domaratskaia EI et al.; It was shown on the model of anemic animals by the method of spleen colonies that non-proliferating CFU-S were resistant against the cytotoxic effect of actinomycin D in concentrations 0.04 to 0.4 micrograms/ml . The entry of CFU-S in proliferation was accompanied by a sharp increase of the sensitivity to the antibiotic in a dose blocking DNA-dependent rRNA synthesis.

Am J Trop Med Hyg, 1983 Mar, 32(2), 231 - 57
Appraisals of compounds of diverse chemical classes for capacities to cure infections with sporozoites of Plasmodium cynomolgi; Schmidt LH; Compounds (265) of widely diverse structures were appraised for radical curative activity in rhesus monkeys infected with sporozoites of the B strain of Plasmodium cynomolgi, using an evaluation system that provided a preliminary assessment with from 0.1-1.0 g of compound and tests against one to five active infections . None of 32 compounds in a miscellaneous structure category, none of seven agents of antibiotic origin, none of 12 1,5-naphthyridines, and none of seven 7-aminoquinolines exhibited curative activity at the largest test doses . There was a suggestion that one of 12 newly synthesized pyrocatechols was curative . Two of 20 6-aminoquinolines effected cure at or near maximum tolerated doses . In contrast, 90 of 174 newly synthesized 8-aminoquinolines effected cure; 18 of the 90 being as active as primaquine, eight twice as active, and six four times as active . There were major disagreements between the above results and those recorded by others in mice inoculated with sporozoites of P . berghei yoelii or P . yoelii nigeriensis . These discrepancies were of serious dimensions in evaluations of the 8-aminoquinolines . This, plus previous near flawless performances of P . cynomolgi in identifying agents that would cure naturally acquired P . vivax infections, led to the suggestion that the abbreviated simian model employed in these studies be used hereafter in primary screening of new agents for radical curative activity.

J Antibiot (Tokyo), 1983 Mar, 36(3), 301 - 11
Studies on the biological activity of stubomycin; Komiyama K et al.; Stubomycin showed direct cytotoxic activity on mammalian cells, yeast, and fungi, and rapid hemolytic activity on mouse erythrocytes . The rate and extent of the cytotoxic and hemolytic activities decreased at lower temperatures . Studies with radioactive precursors revealed that a marginal cytocidal concentration of the antibiotic inhibited synthesis of DNA, RNA, and protein of leukemic cells at almost the same rate . Stubomycin did not show any mutagenicity on mammalian cells and bacteria i.e . the induction of revertants on six bacterial strains, and chromosomal aberrations, sister chromatid exchanges, and the induction of cells resistant to 6-thioguanine on Chinese hamster cells (DON D-6) . The antagonistic effect of various kinds of lipids including phospholipids, cholesterol, olive oil and squalene was studied . Significant antagonism of stubomycin against anti-Saccharomyces cerevisiae activity was observed with phospholipids except for egg lecithin and with cholesterol . The primary action of the antibiotic seems to be to change the cell surface and ultimately the lysis and death of the cells.

Hum Pathol, 1983 Mar, 14(3), 228 - 34
Granulocyte antigen systems and antibodies and their clinical significance; McCullough J; Granulocyte alloantibodies and autoantibodies have a key role in the pathophysiology of several clinical problems . These include febrile transfusion reactions, severe pulmonary reactions to transfusion, isoimmune neonatal neutropenia, failure of effective granulocyte transfusion, autoimmune neutropenia, drug-induced neutropenia, and neutropenias secondary to many other diseases . Although many techniques are available for detecting granulocyte antibodies, the optimal in-vitro tests for predicting the antibodies' clinical effects are not established . Use of indium-111-labeled granulocytes may provide valuable information regarding the in-vivo effects of different granulocyte antibodies . Granulocyte transfusions continue to be used for a limited number of severely infected neutropenic patients who do not respond to antibiotic therapy.

Br J Haematol, 1983 Mar, 53(3), 459 - 66
Adverse effects of aneuploidy on the outcome of remission induction therapy for acute nonlymphocytic leukaemia: analysis of types of treatment failure; Preisler HD et al.; Cytogenetic studies were carried out on bone marrow specimens obtained from 98 patients with acute nonlymphocytic leukaemia . Patients were treated with cytosine arabinoside and an anthracycline antibiotic . The remission rate for patients in whom only normal metaphases were detected (NN patients) was 69% while the remission rates were 50% and 40% respectively for patients in whom both normal and abnormal metaphases were seen (NA patients) and for those in whom only abnormal metaphases were noted (AA patients) . Analysis of remission induction failure types suggests that the differences in outcome were related to a tendency for patients with aneuploid leukaemia to be more likely to have drug resistant disease and to the lesser ability of NA and AA patients to survive and receive a second course of therapy if the first course failed to induce a complete remission.

Clin Exp Immunol, 1983 Mar, 51(3), 517 - 24
Effect of simple sugars on natural killing: evidence against the involvement of a lectin like mechanism in target recognition; Vose BM et al.; The spontaneous lysis of target cells sensitive to natural killer (NK) activity is accomplished in two distinct phases: (i) binding between target and effector cells and (ii) post-binding events leading to target cell destruction . To test the hypothesis that cell surface carbohydrate(s) might be involved in recognitive and/or lytic events, the binding and cytotoxicity of peripheral blood lymphocytes (PBL) towards NK sensitive K-562 targets was studied in the presence of simple sugars and after treatment of the targets with the antibiotic, tunicamycin . Lysis by peripheral blood lymphocytes was found to be inhibited by N-acetyl glucosamine, N-acetyl galactosamine and alpha-methyl mannoside in a dose-dependent manner under conditions where neither these sugars nor those (fucose, galactose) which had little effect on lysis inhibited the binding of effector cells to targets . Further, growth of K-562 in tunicamycin (which inhibits N-linked glycosylations occurring through the lipid intermediate pathway) with or without subsequent treatment with the enzyme neuraminidase, markedly reduced cell surface expression of sugars monitored by lectin binding . Treated cells showed no loss of NK susceptibility and were frequently more sensitive to lysis . Sugar inhibition profiles were the same as for untreated cells . These data suggest that carbohydrates are not the target sites of NK recognition but that simple sugars may have an inhibitory action at a later stage of the lytic process.

J S Afr Vet Assoc, 1983 Mar, 54(1), 67 - 8
The danger of immunising Boergoats against heartwater; Gruss B; Ten 6-toothed Boergoat does and 215 Boergoat kids were injected by the intravenous route with the Onderstepoort heartwater blood vaccine and then temperatured daily . On Day 10, all the does had rectal temperatures in excess of 40 degrees C and were treated with oxytetracycline intravenously, while the kids received an intramuscular injection of the antibiotic . One kid died from heartwater on Day 11 . On Day 15, 7 does had a febrile reaction and all the does and kids were treated as before . Two does died of heartwater on Days 16 and 17 respectively, while 12 kids developed heartwater on Day 17 and 6 kids on Day 18 . All were treated for heartwater . A total of 2 does (20%) and 16 kids (7.4%) died during the experiment.

J Pharmacol Exp Ther, 1983 Mar, 224(3), 685 - 91
Inactivation of cytochrome P-450 by a troleandomycin metabolite . Protective role of glutathione; Pessayre D et al.; Troleandomycin, a macrolide antibiotic, has been shown to be demethylated and oxidized into a metabolite which forms an inactive complex with the iron(II) of cytochrome P-450 . The role of glutathione in the metabolism of troleandomycin was investigated . Administration of troleandomycin (1 mmol X kg-1 p.o.) decreased the concentration of glutathione in the liver . The depletion of glutathione was increased in rats pretreated with phenobarbital and decreased in rats pretreated with CoCl2 . In vitro, an inverse relationship was found between the concentration of glutathione in the incubation mixture and the appearance of the cytochrome P-450-troleandomycin metabolite complex . Glutathione, however, did not inhibit the demethylation of troleandomycin and did not destroy the cytochrome P-450-troleandomycin metabolite complex . The in vitro protective effect of glutathione was reproduced by cysteine but not by glycine . In vivo, decreasing the concentration of glutathione in the liver by food deprivation or by the administration of diethylmaleate increased the formation of the cytochrome P-450-troleandomycin metabolite complex . These results indicate that glutathione is depleted by a troleandomycin metabolite in vivo, whereas glutathione protects against the formation of the inactive cytochrome P-450-troleandomycin metabolite complex in vitro and in vivo.

Cancer Treat Rev, 1983 Mar, 10(1), 1 - 22
4'-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data; Ganzina F; 4'-epi-doxorubicin (4'-epi-DX) is a new anthracycline antibiotic . It differs from doxorubicin (DX) by the epimerization of the OH group in position 4' of the aminosugar moiety, and was synthesized in an effort to find agents with a superior therapeutic index to the parent compound doxorubicin (DX) . 4'-epi-doxorubicin binds to DNA and inhibits nucleic acid synthesis and function . The antitumor activity of 4'-epi-DX in several experimental tumors (Leukemias L 1210, P 388, Gross Leukemia, Sarcoma 180 ascitic and solid, C3H/HE mammary carcinoma) is similar to that of DX . However, 4'-epi-doxorubicin has greater antitumor activity than doxorubicin in Lewis lung carcinoma, MS-2 sarcoma lung metastasis, and human melanoma in athymic mice . In chronic toxicity studies there were no qualitative differences between 4'-epi-DX and DX; quantitatively, however, 4'-epi-DX was less toxic . In different experimental models 4'-epi-DX has been shown to be less cardiotoxic than its parent compound . In chronic toxicity studies in the rabbit, histopathologic findings revealed the same pattern of cardiotoxicity for both drugs but less marked with 4'-epi-DX . Distribution studies in mice with tumors showed a lower concentration of 4'-epi-DX in the heart, spleen and kidneys; the hepatobiliary metabolism and excretion of 4'-epi-DX investigated in the rat, indicated that the new analogue was more extensively metabolized than the parent compound . Pharmacokinetics of 4'-epi-DX in humans showed a multiexponential decrease of plasma levels; the same pattern was observed for the metabolite 13-OH epidoxorubicinol but with lower concentrations than the unchanged drug . A high plasma clearance (0.9-1.41/min), a terminal half-life of about 30-40 hr and a large volume of distribution were the main pharmacokinetic characteristics of 4'-epi-DX . A reduction of the dose appears to be appropriate in patients with liver function impairment . Phase II studies with 4'-epi-DX have indicated that the drug produces a pattern of acute toxicity, including acute cardiac toxicity, qualitatively similar to that of DX at identical doses but quantitatively lower, with particular regard to leukopenia and gastrointestinal toxicity . The range of single active doses is between 60 and 90 mg/m2, the most frequently employed doses schedules being 75 or 90 mg/m2 i.v . every 3 weeks . 4'-epi-DX has shown activity in a variety of tumors such as breast carcinoma, soft tissues sarcomas, NH lymphomas, leukemias, ovarian cancer and gastric cancer . Preliminary evidence of activity has been found in melanoma, rectal cancer and pancreatic cancer suggesting a broad spectrum of activity . As to chronic cardiac toxicity up to now only 2 mild to moderate and reversible CHF have been observed at doses of 1120 and 1235 mg/m2 in about 700 treated patients . Specific and comparative studies are in progress: preliminary findings from a randomized comparison of 4'-epi-DX vs DX in breast cancer indicated that 4'-epi-DX may have a lower cumulative cardiotoxicity.

Rev Infect Dis, 1983 Mar-Apr, 5 Suppl 1, S40 - 54
Empiric therapy for pneumonia; Donowitz GR et al.; Bacterial pneumonia remains a serious infectious disease even in the modern era of antibiotics and still causes significant morbidity and mortality . Because of the large number of organisms that may cause pulmonary disease, the inexactness of commonly used diagnostic techniques, and the serious consequences of untreated disease, empiric therapy has become accepted practice . Empiric therapy should be designed for treatment of the most likely etiologic organisms while minimizing the potential adverse effects of "shotgun" therapy: drug toxicity, superinfection, and excessive cost . The recognition of common pneumonia syndromes helps narrow the spectrum of possible etiologic agents and consequently aids in the design of rational empiric antibiotic therapy.

Antibiotiki, 1983 Mar, 28(3), 192 - 4
{Effect of heliomycin on the respiration and oxidative phosphorylation of the liver mitochondria of the rat}; Konoshenko GI et al.; The effect of heliomycin and known uncouplers of oxidative phosphorylation on respiration and oxidative phosphorylation was studied comparatively . Heliomycin, as well as 2,4-dinitrophenol, valinomycin and gramicidin S inhibited the mitochondrial synthesis of ATP . This process was inhibited completely by heliomycin at a concentration of 1.5 x 10(-5) M . The synthesis of inorganic pyrophosphate, the other macroergic compound, was also inhibited by heliomycin, ATPase and pyrophosphatase of uncoupled mitochondria being not inhibited by the antibiotic . Like 2,4-dinitrophenol, heliomycin stimulated the synthesis of ATPase and respiration in intact mitochondria . Probably, heliomycin inhibited the synthesis of ATP and pyrophosphate by uncoupling the processes of respiration and oxidative phosphorylation . It was shown earlier that heliomycin, a specific inhibitor of bacterial RNA synthesis, also affected energy metabolism of bacterial cells by inhibiting the synthesis of ATP and active transport.

Isr J Med Sci, 1983 Mar, 19(3), 267 - 70
Late postoperative fever--viral infection following multiple blood transfusion; Siegman-Igra Y; The possibility of acquiring a viral infection by blood transfusion, although recognized for nearly 20 yr, is often ignored . Surgeons and internists submit patients to sophisticated, and sometimes invasive, diagnostic and therapeutic procedures without considering this possibility . We report here on two patients in whom febrile illness appeared about 5 wk after surgery . Both had received multiple blood transfusions in the perioperative period . Initial diagnoses indicated typhoid fever in one patient who received chloramphenicol therapy, and endocarditis in the other patient who was given massive combined antibiotic therapy . Both were later diagnosed by serologic methods as having cytomegalovirus and Epstein-Barr virus infection, respectively . Review of the literature reveals that this mechanism of acquiring these frequently asymptomatic viral infections is surprisingly common.

J Pharmacol Exp Ther, 1983 Mar, 224(3), 609 - 13
Effect of aminophylline on amphotericin B nephrotoxicity in the dog; Gerkens JF et al.; The polyene antibiotic, amphotericin B, causes an acute reduction in renal blood flow and glomerular filtration rate . The purpose of this study was to evaluate the hypothesis that the renal vascular response to amphotericin B can be blocked by aminophylline . Toward this end, the effect of aminophylline on the renal response to amphotericin B in sodium-depleted dogs was examined . In dogs not treated with aminophylline, amphotericin B (0.5 mg/kg infused i.v . over 20 min) significantly reduced renal blood flow and glomerular filtration by 49.9 +/- 12.6 ml/min (mean +/- S.E.M.) and 23.4 +/- 2.4 ml/min, respectively at 140 min after the amphotericin B infusion . In dogs treated with an intrarenal aminophylline infusion (5 mg/min), the renal blood flow and glomerular filtration rate response to amphotericin B did not differ from that of amphotericin B vehicle . We conclude that aminophylline inhibits the renal response to amphotericin B . The possible clinical relevance of these observations are discussed.

Antimicrob Agents Chemother, 1983 Mar, 23(3), 360 - 3
Effects of moxalactam and cefuroxime on mitogen-stimulated human mononuclear leukocytes; Manzella JP et al.; The effect of moxalactam and cefuroxime on mitogen-stimulated human peripheral blood mononuclear leukocytes was studied . Mononuclear leukocytes, mitogen, and antibiotic were added to microtiter wells . Cells were cultured for 3 days, pulsed with tritiated thymidine, and then counted . Compared with control cell cultures, treated cultures showed phytohemagglutinin responsiveness to be depressed by the addition of moxalactam at concentrations of 25 to 200 micrograms/ml (P less than 0.001) and by cefuroxime at concentrations of 50 to 200 micrograms/ml (P less than 0.02 to P less than 0.01) . The depressive effect on blastogenesis was less marked when concanavalin A was used . Unstimulated lymphocyte transformation responses were also depressed by both antibiotics at all concentrations (P less than 0.05) . Preincubation of mononuclear leukocytes with antibiotic for 2 h, followed by washing and culturing in an antibiotic-free medium, did not depress transformation response . When antibiotic was added 24 h after mitogen, depression of response was insignificant . The data from this study suggest that two new beta-lactam antibiotics, at concentrations achievable in serum when used therapeutically, may have immunosuppressant effects . It remains to be established whether these effects are clinically important.

J Hosp Infect, 1983 Mar, 4(1), 65 - 9
Metronidazole need not be combined with an aminoglycoside when used for prophylaxis in elective colorectal surgery; Morris DL et al.; A prospective randomized controlled study has compared prophylactic intravenous metronidazole alone with the combination of metronidazole and gentamicin in 100 patients having elective colorectal surgery . There was no significant difference in mortality, infection, dehiscence or postoperative stay between the antibiotic groups . Postoperative sepsis was almost entirely due to aerobic organisms but was associated with minimal morbidity . A significantly higher rate of anastomotic dehiscence and postoperative infection was seen where the quality of bowel preparation was judged to be poor.

Br J Clin Pharmacol, 1983 Mar, 15(3), 339 - 46
Effect of cephapirin on tubular reabsorption of amino acids, uric acid and beta 2-microglobulin in man; Arvidsson A et al.; Cephapirin, a beta-lactam antibiotic, was administered intravenously to five healthy subjects in a dose of 1 g . Renal clearances of cephapirin, beta 2-microglobulin, uric acid and amino acids were measured during the experiment and compared to timed control data, i.e . when no cephapirin was given . Renal clearance of cephapirin decreased when plasma concentrations declined . As protein binding of cephapirin is constant over a wide plasma concentration range, this finding may indicate that cephapirin is reabsorbed in the kidney by a saturable process . Renal clearance of endogenous amino acids, particularly those belonging to the basic group increased after cephapirin . There was no change in renal clearance of beta 2-microglobulin which excludes a general toxic effect on tubular reabsorption of endogenous substances caused by cephapirin . A flow dependent increase of uric acid clearance was observed . Our results are suggestive of a competition between cephapirin and amino acids for some common step in the tubular reabsorption process.

Cancer Res, 1983 Mar, 43(3), 1049 - 53
Effects of iron, copper, cobalt, and their chelators on the cytotoxicity of bleomycin; Lin PS et al.; Bleomycin is widely used for treating several types of human tumors as well as a variety of experimental tumors . The ability of this antibiotic to bind and to damage DNA has been proposed to be responsible for its antitumor effect . Bleomycin is also a good chelator for several metals, e.g., iron, copper, and others . Bleomycin:metal complexes have been investigated in detail particularly for their action on isolated DNA . The conclusions from these studies indicate that metal-chelated bleomycin either is ineffective or more effective in damaging DNA . In this paper, we tested the effect of iron, copper, cobalt, and their chelators on bleomycin cytotoxicity . Our results suggest that chelating bleomycin with copper or adding an iron chelator (deferoxamine), diethylenetriamine pentaacetic acid, and a copper chelator (penicillamine) shows no effect on bleomycin cytotoxicity . On the other hand, iron dextran and a metal chelator, diethyldithiocarbamate (DDC), with bleomycin show enhanced cytotoxicity . Cobalt-chelated bleomycin is not cytotoxic but is cytotoxic when combined with DDC . We suggest that different mechanisms are contributing to the enhanced toxicity of bleomycin with iron dextran and DDC . Bleomycin acts as a ferrous oxidase which promotes the iron toxicity . In the case of DDC, it can act as a reducing agent or it can help to maintain the bleomycin:metal complex in the reduced form which can generate radicals.

Presse Med, 1983 Feb 26, 12(9), 553 - 6
{Chemoprevention with intravenous doxycycline in 40 cases of colonic esophagoplasty}; Saux P et al.; Doxycycline was used to prevent infection in 40 patients undergoing oesophageal surgery (for carcinoma in 35 and for benign lesions in 5) . Treatment began with induction of anaesthesia and continued in doses of at least 200 mg/day for a mean period of 10 days . Concentrations of the antibiotic were measured in the serum and colonic tissue of 20 patients, 2 hours on average after the first injection . Mean serum and tissue levels were 4.1 +/- 0.8 mcg.ml-1 and 2.9 +/- mcg.ml-1 respectively, with a tissue to serum ratio of 0.7 . This ratio remained practically unchanged between the first and fourth hours post-injection . Doxycycline was successful in preventing post-operative infection in 75% of the cases . No infection due to anaerobic organisms was observed.

J Biol Chem, 1983 Feb 25, 258(4), 2098 - 101
Thermal regulation of membrane fluidity in Escherichia coli . Effects of overproduction of beta-ketoacyl-acyl carrier protein synthase I; de Mendoza D et al.; Multicopy plasmids bearing the structural gene (fabB) for beta-ketoacyl-acyl carrier protein (ACP) synthase I were constructed in vitro and transformed into various Escherichia coli strains . Introduction of these plasmids into fabB strains resulted in a fabB+ phenotype and a large (8- to 10-fold) overproduction of synthase I activity . Strains carrying these plasmids were also unusually resistant to cerulenin (an antibiotic that specifically inhibits beta-ketoacyl-ACP synthase activity) and overproduced cis-vaccenic acid . Strains (fabF-) lacking beta-ketoacyl-ACP synthase II are deficient in both cis-vaccenic acid synthesis and thermal regulation . Introduction of the fabB plasmids into these strains resulted in the restoration of cis-vaccenic acid synthesis . However, the plasmid-engendered cis-vaccenic acid synthesis of these strains was unaffected by temperature . These results demonstrate that synthase II, the product of the fabF gene, is the sole enzyme regulating the temperature-dependent composition of the membrane phospholipid acyl chains.

J Biol Chem, 1983 Feb 10, 258(3), 1775 - 80
Effect of tunicamycin, an inhibitor of protein glycosylation, on the biological properties of acetylcholine receptor in cultured muscle cells; Prives J et al.; We have studied the effect of tunicamycin (TM), an antibiotic which inhibits the glycosylation of nascent proteins, on the properties of the acetylcholine receptor (AChR) at the surface of embryonic chick skeletal muscle cells . The use of two separate assays, specific binding of 125I-alpha-bungarotoxin and carbamylcholine-activated 22Na+ uptake, has allowed us to monitor the effects of impaired glycosylation on the metabolic and functional properties of AChR . A significant decrease in the amounts of surface AChR elaborated in the presence of TM is detected by both measurements . This decrease has been found to reflect an enhanced proteolytic degradation of the underglycosylated AChR . The underglycosylated AChR, expressed on the cell surface in the presence of TM, retains the capability of mediating agonist-activated ionic permeability changes, but displays quantitatively altered interactions with receptor ligands . We conclude that the carbohydrate moiety on AChR may play a role in determining the folding of newly synthesized polypeptides to form a conformation compatible with the metabolic properties and ligand interactions characteristic of glycosylated AChR.

Biochem Biophys Res Commun, 1983 Feb 10, 110(3), 959 - 66
Identification of a key structural feature of cobalt(III)-bleomycins: an exogenous ligand (e.g . hydroperoxide) bound to cobalt; Chang CH et al.; A series of cobalt(III) complexes of the anticancer antibiotic bleomycin has been prepared . Mass spectrometry and enzymatic analysis show that the green cobalt-bleomycin complex contains a hydroperoxide (-OOH) group bound to cobalt with unusual stability . Under appropriate conditions, cobalt-bleomycins containing other monodentate ligands to cobalt can be formed; fast-atom bombardment mass spectra of such complexes show peaks for cobalt-bleomycin at the expected mass, and also peaks for the intact complexes at the required higher mass.

Nord Vet Med, 1983 Feb, 35(2), 91 - 4
The effect of colistin feeding during the mating, gestation and lactation periods on whelping result in mink; Pekkanen T et al.; Colistin (100000 IU/kg) was given in the feed during the mating, gestation and lactation periods to 49 female standard minks . 99 similar animals served as control without the antibiotic . The whelping result, expressed as the number of puppies living three weeks post partum per mated female, was 3.22 in the experimental group and 2.67 in the control group . The difference in the whelping result between the groups was mainly due to the significantly greater number of empty females in the control group compared to the experimental group.

Mutat Res, 1983 Feb, 107(2), 433 - 45
Characterization of chloramphenicol- and 8-azaguanine-resistant mutants isolated from a continuous rat-liver epithelial cell line; Sudilovsky O et al.; 2 non-tumorigenic, chloramphenicol- and 8-azaguanine-resistant strains have been isolated from the rat-liver cell line K-22, by a 2-step mutagenesis procedure . Their chromosome composition and growth properties have been characterized . Failure of chloramphenicol to inhibit mitochondrial protein synthesis in one of the clones, F1, strongly suggests that resistance to the antibiotic in this strain is due to a mutation in mitochondrial DNA.

J Neurosurg, 1983 Feb, 58(2), 270 - 4
Aspergillus infections of the lumbar disc spaces . Report of three cases; Mawk JR et al.; Three cases of lumbar vertebral interspace infection due to the Aspergillus fungus are presented . Two patients responded to vigorous surgical therapy in combination with prolonged administration of antifungal agents . The third patient died of complications related to the antibiotic therapy . Possible etiologies of this unusual problem are reviewed in light of the changing spectrum of nosocomial and spontaneously acquired infectious processes . Combined aggressive medical and surgical therapy is discussed with respect to the known difficulties in eradicating deep-seated osseous mycotic infections.

J Clin Gastroenterol, 1983 Feb, 5(1), 55 - 8
Nonhealing duodenal ulceration due to candida; Thomas E et al.; An important role for candida in gastric and duodenal ulcer disease is being increasingly recognized . Causative factors implicated include the frequent use of cimetidine, and immunosuppressive or antibiotic therapy . Concerning cimetidine, there is no clear-cut evidence that the drug depresses cell mediated immunity; on the contrary, there is evidence that delayed hypersensitivity is enhanced . Acid reduction is the alternate and more likely explanation for any role of cimetidine in gastric and duodenal candidiasis . We report a patient with a duodenal ulcer, which repeatedly bled and failed to heal in hospital on standard antacid and cimetidine therapy . Candida was identified in the ulcer and treated, using mycostatin suspension, resulting in complete healing . We feel that candida involvement of duodenal ulcers may be more common than is generally recognized, and may be the cause for nonhealing in certain patients already on optimum therapy.

J Clin Microbiol, 1983 Feb, 17(2), 349 - 51
Fusobacterium nucleatum pericarditis; Truant AL et al.; A pericardial effusion was diagnosed by echocardiography in a 49 year old man who suffered acute cough, orthopnea, and chest pain . Because of a positive tuberculin skin test, mycobacteria were initially suspected as the cause of the pericarditis . The patient was therefore treated with antituberculosis drugs . The pericardial effusion failed to resolve, however, and pericardiectomy was performed . Culture of the pericardial fluid yielded pure Fusobacterium nucleatum growth . The patient responded to antibiotic therapy and was in good health 3 weeks after being discharged from the hospital . This represents the first report of F . nucleatum pericarditis.

J Cell Biol, 1983 Feb, 96(2), 363 - 72
Distribution of filipin-sterol complexes on cultured muscle cells: cell-substratum contact areas associated with acetylcholine receptor clusters; Bridgman PC et al.; Specialized areas within broad, close, cell-substratum contacts seen with reflection interference contrast microscopy in cultures of Xenopus embryonic muscle cells were studied . These areas usually contained a distinct pattern of light and dark spots suggesting that the closeness of apposition between the membrane and the substratum was irregular . They coincided with areas containing acetylcholine receptor clusters identified by fluorescence labeled alpha-bungarotoxin . Freeze-fracture of the cells confirmed these observations . The membrane in these areas was highly convoluted and contained aggregates of large P-face intramembrane particles (probably representing acetylcholine receptors) . If cells were fixed and then treated with the sterol-specific antibiotic filipin before fracturing, the pattern of filipin-sterol complex distribution closely followed the pattern of cell-substratum contact . Filipin-sterol complexes were in low density in the regions where the membrane contained clustered intramembrane particles . These membrane regions were away from the substratum (bright white areas in reflection interference contrast; depressions of the P-face in freeze-fracture) . Filipin-sterol complexes were also in reduced density where the membrane was very close to the substratum (dark areas in reflection interference contrast; bulges of the P-face in freeze-fracture) . These areas were not associated with clustered acetylcholine receptors (aggregated particles) . This result suggests that filipin treatment causes little or no artefact in either acetylcholine receptor distribution or membrane topography of fixed cells and that the distribution of filipin-sterol complexes may closely parallel the microheterogeneity of membranes that exist in living cells.

J Cell Physiol, 1983 Feb, 114(2), 162 - 72
The biochemical and ultrastructural effects of tunicamycin and D-glucosamine in L1210 leukemic cells; Morin MJ et al.; Tunicamycin was found to specifically inhibit the incorporation of a number of sugars into L1210 leukemia cell glycoproteins . This inhibition of glycoprotein biosynthesis led to a cessation of cell growth which was reversible in a dose-dependent and time-dependent manner . After removal of the antibiotic from L1210 cell cultures resumption of sugar incorporation preceded that of thymidine incorporation and the recovery of cell growth . The treatment of cells with tunicamycin resulted in a significant increase in the intracellular pool of UDP-N-acetylglucosamine which occurred concurrently with alterations in cell ultrastructure including distentions of the endoplasmic reticulum and nuclear membranes . Similar ultrastructural changes and increases in the intracellular pools of UDP-sugars were observed in L1210 cells exposed to 5 mM D-glucosamine, which suggested that the antiproliferative effects of tunicamycin may be related to the accumulation in the endoplasmic reticulum of one or more nucleotide sugar precursors of asparagine-linked glycoprotein biosynthesis . However, the biological effects of tunicamycin could be distinguished from those caused by D-glucosamine . Exposure of L1210 cells to tunicamycin resulted in specific alterations in the biochemical composition of the plasma membrane and in the inhibition of cellular agglutination by wheat germ agglutinin which were not apparent following exposure to equitoxic concentrations of the aminosugar . These studies, together with those which demonstrated that recovery of the cellular capacity to synthesize glycoproteins was obligatory for the recovery of cellular proliferation in tunicamycin-treated cells, suggested that inhibition of the synthesis of glycoproteins was the major factor limiting L1210 leukemic cell proliferation.

J Bone Joint Surg Am, 1983 Feb, 65(2), 230 - 4
Osteomyelitis of the pelvis in children; Highland TR et al.; We reviewed the records of sixteen patients with osteomyelitis of the pelvis, all of whom were fifteen years old or younger . Eleven of the patients were followed for an average of 3.5 years (range, two to nine years) . Pelvic osteomyelitis in children is an uncommon lesion . Review of the literature gives the impression that this lesion is usually diagnosed late in its course and requires surgical drainage for adequate treatment . The role of the technetium bone scan in making an early diagnosis is important . All of the patients in this series were treated with antibiotic therapy alone, and surgical drainage was not found to be necessary . All of the patients who were followed for at least two years had no recurrence and no permanent sequelae.

Dis Colon Rectum, 1983 Feb, 26(2), 116 - 8
Survival after colonic perforation during barium-enema examination . Modified radical surgical debridement; Hardy TG Jr et al.; Four of five patients survived perforation of the colon incidental to barium-enema examination, while the other survived without sequela of infection until hemiplegia and pneumonia supervened two and 36 days, respectively, postoperatively . It is postulated that adequate intravenous fluids, early operation, with complete cleansing by antibiotic irrigation and mechanical debridement of the abdominal cavity, along with excision of the perforated segment of bowel with establishment of an end colostomy or ileostomy and distal mucous fistula, if possible, are keys to survival in these patients . Triple antibiotics, using ampicillin, gentamicin, and clindamycin, or metronidazole, should be administered in all patients as soon as the diagnosis is made, and continued postoperatively as indicated until there is no evidence of infection . An intraluminal intestinal tube, for stichless plication of the small bowel, may be helpful in some patients . A stomacone should be used for a barium enema through a colostomy stoma . Care should be exercised in performing barium contrast studies in patients with inflammatory bowel disease.

Cancer, 1983 Feb 1, 51(3), 378 - 80
Phase I study of L-alanosine (NSC 15353); Goldsmith MA et al.; L-alanosine (NSC 15353) is a newly developed antitumor antibiotic which acts as an inhibitor of purine intermediary metabolism . Experimental antitumor activity was demonstrated in a variety of murine neoplasms . A Phase I trial was undertaken on a daily x 5 (d x 5) schedule in 22 evaluable patients . Dose limiting toxicity was an oral mucositis characterized by beefy red oral, lingual and pharyngeal erythema . The maximum tolerated dose is 320 mg/m2/d x 5 every three weeks . The recommended dose for Phase II evaluation is 160 mg/m2/d x 5 every three weeks.

Jpn J Antibiot, 1983 Feb, 36(2), 391 - 7
{Cooperative studies on clinical effect of cefotetan for severe infections combined with hematologic disorders}; Shinohara Y et al.; Seventy-six patients with severe infection accompanying hematologic disorders including leukemia and lymphoma were treated with intravenous drip infusion of cefotetan (CTT) . Of the 66 cases in whom the efficacy could be evaluated, 22 cases responded markedly and 16 cases moderately, the effective rate being 57.6% . It is impressed that more cases responded markedly to CTT than to any other antibiotics previously studied . None of the cases revealed serious side effects attributable to CTT . These results indicate that CTT is an effective and safe antibiotic for the treatment of severe infection accompanying hematologic disorders . As CTT was administered to special cases under marked decrease of neutrocyte, the importance of neutrocyte in the treatment of infection was also indicated.

Antibiotiki, 1983 Feb, 28(2), 83 - 6
{Characteristic features of protoplast formation and regeneration in Fusidium coccineum}; Zakharova GM et al.; The methods for preparation and regeneration of protoplasts were tested with respect to the strains of F . coccineum markedly differing in their capacity for antibiotic production, sporulation and the growth rate . It was found that the substrate used for the culture growth had a significant effect on the cell wall and sensitivity of the mycelium to lytic enzymes . An enzyme from Hellix pomatia and its combination with lysozyme were used for lysing the culture . The cytological investigation of the time course of the culture lysis revealed a stage-by-stage pattern of protoplast formation by means of fragmentation of the hyphal contents till a ball was formed . Two to 4 protoplasts differing in their size and structure were formed within a cell . The pH value and osmotically stabilizing component had some effect on the rate of protoplast formation . Highly productive strains were characterized by formation of protoplasts heterogenous in their size and by decreased frequency of regenerations . The enzyme-free protoplasts preserved their viability and capacity for germination in osmotically stabilizing media for 72-96 hours of storage at 4 degrees C . On solid media the regeneration frequency reached 38 per cent . The regenerated cells formed colonies morphologically similar to those of the intact culture.

J Parasitol, 1983 Feb, 69(1), 129 - 37
Freeze-fracture localization of filipin-cholesterol complexes in the plasma membrane of Trypanosoma cruzi; Souto-Padron T et al.; The polyene antibiotic filipin was used as a probe for the detection of cholesterol on the P and E faces of the cell body and the flagellar membranes of epimastigotes of Trypanosoma cruzi . When glutaraldehyde-fixed cells were treated with filipin the filipin-cholesterol complexes were homogenously distributed throughout the parasite's plasma membrane . In some cells, mainly on their P faces, such complexes were arranged linearly forming parallel bands with a distance between the bands similar to that existent between the subpellicular microtubules that are attached to the plasma membrane . Filipin-cholesterol complexes were more abundant in the flagellar membrane than in the membrane that enclosed the cell body . No filipin-cholesterol complexes were seen in the membrane of intracellular organelles . Treatment of living epimastigotes with filipin-induced aggregation of cholesterol and intramembranous particles.

J Pharmacobiodyn, 1983 Feb, 6(2), 139 - 40
Covalent binding of cefotaxime to human serum albumin; Toyo'oka T et al.; The covalent binding ratio of cephalosporins (CEZ, CER, CET and CTX) to human serum albumin was examined at pH 7 and pH 10 . The antibiotic equivalents were larger at pH 10 than at pH 7 . The degree in the binding ratio of the 4 cephalosporins was CET greater than CER greater than CTX greater than CEZ at pH 7 and CER greater than CET greater than CTX greater than CEZ at pH 10.

Res Commun Chem Pathol Pharmacol, 1983 Feb, 39(2), 311 - 9
The effect of pyrrolnitrin on mitochondrial reactions: the induction of swelling; Kawai K et al.; An antifungal antibiotic, pyrrolnitrin, was found to show very similar biological activities to those of imidazole antimycotics on isolated mitochondria . Pyrrolnitrin caused drastic swelling of mitochondria in isotonic solutions of alkali metal salts and of sucrose without any addition of substrate for the respiratory chain in mitochondria . The swelling induced by pyrrolnitrin was characterized by a biphasic swelling process; a very fast initial swelling and thereafter a very slow speed secondary swelling . The increase of pyrrolnitrin concentration exponentially increased the magnitude of over-all rapid swelling . Pyrrolnitrin enhance the latent ATPase activity of mitochondria at the similar range of concentrations to those needed for the induction of the swelling . The concentrations of pyrrolnitrin where mitochondrial swelling was induced were found to be far lower than those needed for the exhibition of inhibitory effect on the electron transport system of mitochondria.

Am J Dis Child, 1983 Feb, 137(2), 118 - 22
Vasculitis, pulmonary cavitation, and anemia during antithyroid drug therapy; Cassorla FG et al.; Two thyrotoxic girls, aged 12 and 16 years, had a clinical picture consisting of purpuric skin rash, nephritis, pulmonary cavitation, hemoptysis, and profound anemia during antithyroid drug therapy . These major toxic manifestations prompted discontinuation of antithyroid drugs and institution of antibiotic and glucocorticoid therapy before the resolution of the severe illness . The girls eventually required ablative doses of radioactive iodine, and one of them had a thyroidectomy for the treatment of thyrotoxicosis . The skin biopsy specimen in one patient was indicative of mononuclear cell cutaneous vasculitis . After recovery, the patients had no evidence Of persistent anemia, nephritis, or pulmonary parenchymal disease.

J Ultrastruct Res, 1983 Feb, 82(2), 143 - 55
Variability of the topography of low-density lipoprotein (LDL) receptors in the plasma membrane of cultured human skin fibroblasts as revealed by gold-LDL conjugates in conjunction with the surface replication technique; Robenek H et al.; In this investigation the membrane-perturbing effect of filipin, a polyene antibiotic which reacts specifically with cholesterol or cholesterol-like compounds in cell membranes, has been exploited to study the distribution of coated pits in cultured human skin fibroblasts . The coated pits, showing no filipin-cholesterol complexes, occurred singly or in clusters without apparent localization of either type to a particular region of the fibroblast membrane . Colloidal gold, conjugated to low-density lipoprotein, has proven to be an excellent marker, allowing the localization of low-density lipoprotein receptors on the surface of cultured cells . A pattern similar to that for the coated pits in the plasma membrane fracture faces was observed in the distribution of gold-low-density lipoprotein conjugates in surface replicas, indicating that the low-density lipoprotein receptors are associated with these coated pits . It was shown that there is an apparent heterogeneity in the distribution of low-density lipoprotein receptors, from cell to cell and even among different areas of the same cell membrane . The binding capacity for gold-low-density lipoprotein complexes, as represented by the extent of surface labeling, was directly related to the cell variety within the culture or to the particular experimental procedure . The observation of differences in the distribution of gold-low-density lipoprotein conjugates, even among adjacent coated pits, provides evidence for various stages of activity of the low-density lipoprotein receptors corresponding to incorporation, mobility, and internalization.

Biochem Biophys Res Commun, 1983 Jan 27, 110(2), 483 - 90
Repair of potentially lethal and sublethal damage induced by neocarzinostatin in normal and ataxia-telangiectasia skin fibroblasts; Shiloh Y et al.; Neocarzinostatin is a radiomimetic antibiotic with a potent cytotoxic effect which elicits a hypersensitive response in human cells homozygous or heterozygous for the gene for ataxia-telangiectasia . The extent and the time course of potentially lethal damage repair and sublethal damage repair following neocarzinostatin treatment were investigated in human skin fibroblast strains and were found to be remarkably similar to those obtained following X-irradiation . Ataxia-telangiectasia homozygous cells essentially lacked potentially lethal damage repair, but were able to perform some degree of sublethal damage repair following neocarzinostatin treatment . Ataxia-telangiectasia heterozygous cells which show an intermediate degree of neocarzinostatin sensitivity could perform both processes but with somewhat reduced efficiency as compared to normal cells . These observations provide further evidence for a DNA repair defect in ataxia-telangiectasia cells.

FEBS Lett, 1983 Jan 24, 151(2), 219 - 22
Compound 48/80-induced permeability change in liposomal membrane; Katsu T et al.; The action of compound 48/80 (a mixture of condensation products of p-methoxy-N-methylphenethylamine with formaldehyde) on liposomal membranes was studied by means of K+-loaded liposomes and a K+ ion-selective electrode . Prompt efflux of K+ was detected when 48/80 was added to the negatively charged liposome suspension, while the monomer of 48/80, p-methoxy-N-methylphenethylamine, did not release K+ from the same liposomes . The mechanism for the action of 48/80 is discussed in comparison with that of a polymyxin, well known as an antibiotic acting on bacterial membranes.

Wien Klin Wochenschr, 1983 Jan 21, 95(2), 52 - 5
{Pharmacokinetics and acute signs of cardiac toxicity during doxorubicin therapy}; Lenzhofer R et al.; Doxorubicin (Adriamycin) has shown impressive activity in the treatment of a broad spectrum of malignant tumours . Chronic irreversible cardiac myopathy is the usual cumulative dose-limiting toxicity with this anthracycline antibiotic . In this study acute cardiac reactions following doxorubicin infusions (60 mg/m2) were registered by means of ECG Holter monitoring and measurement of systolic time intervals . The PEPI as well as the PEP/LVET ratio were found to be significantly increased, with a peak at 6 hours following drug infusion (p less than 0.001) . This observation proves the occurrence of transient myocardial dysfunction during doxorubicin treatment . Pharmacokinetic data showed good correlation between the electrocardiographic changes and the tissue distribution of the drug . Doxorubicin-related ventricular arrhythmias were observed in only 2 out of 6 cases . Repeated acute myocardial damage by doxorubicin infusions is considered to be the cause of chronic cardiomyopathy with long-term administration.

ZFA (Stuttgart), 1983 Jan 20, 59(2), 79 - 80
{Emergency in general medicine (43) . Septic complications in implanted IUD}; Kuhn W; PIP: Between 2-6% of patients with an IUD will suffer related ascending infections of the inner genital region with possible spread to the pelvic region, independent of length of use . In case of pregnancy with an IUD, septic complications will be more severe . None of the IUD models is regarded as causing infection since the Dalkon Shield has been taken off the market . The symptomatology of the disease develops similar to an uncomplicated ascending adnexitis . It will cause diagnostic problems if it cannot be determined whether the septic focus is located in the inner genital region . With uncharacteristic or absent pathological and gynecological findings by touch, a septic ovarial vein thrombosis has to be considered . The search for the IUD, even with a nonvisible thread, by ultrasound is unavoidable . Further measures include control of the kidney and pulmonary function and leukocytes and blood sedimentation . If an infection develops with an implanted IUD, which is to be classed with the inner genital region, antibiotic therapy can be started provided that no shock signs, no acute abdomen, and no grave feelings of illness are present . If the patient is pregnant it is absolutely necessary to send her to the hospital for examination, even if there are no grave symptoms .

Eur J Biochem, 1983 Jan 17, 130(1), 27 - 32
Association of the prolipoprotein accumulated in the presence of globomycin with the outer membrane of Escherichia coli; Inukai M et al.; The prolipoprotein, a secretory precursor of the outer membrane lipoprotein of Escherichia coli, is known to be accumulated in the cell envelope when cells are grown in the presence of a cyclic antibiotic, globomycin . The prolipoprotein was localized in the cytoplasmic membrane when it was separated from the outer membrane by sucrose-density gradient centrifugation . However, when the envelope fraction was treated with sodium sarcosinate, the prolipoprotein was found almost exclusively in the sarcosinate-insoluble outer membrane fraction . The prolipoprotein separated in the cytoplasmic membrane by sucrose-density gradient centrifugation was soluble in sarcosinate and could not form a complex with the outer membrane once solubilized in sarcosinate . Labeling of the two lysine residues at positions 2 and 5 of the prolipoprotein with {3H}dinitrophenylfluorobenzene was enhanced 26-fold when the cells were disrupted by sonication . On the other hand, a tryptic fragment of the ompA protein, which is known to exist in the periplasmic space, increased its susceptibility to {3H}dinitrophenylfluorobenzene only 5.3-times upon disruption of the cell structure . These results indicate that the prolipoprotein accumulated in the presence of globomycin is translocated across the cytoplasmic membrane and interacts with the outer membrane . At the same time, it is attached to the cytoplasmic membrane with its amino-terminal signal peptide in such a way that the amino-terminal portion of the signal peptide containing two lysine residues is left inside the cytoplasm.

Biochim Biophys Acta, 1983 Jan 13, 722(1), 43 - 50
Inhibition of mitochondrial oxidative phosphorylation by adriamycin; Muhammed H et al.; The antitumour antibiotic, adriamycin, inhibited oxidative phosphorylation in freshly prepared mitochondria from the heart, liver and kidney of the rat . It abolished respiratory control and stimulated ATPase activity . Succinate oxidation by heart mitochondria was extremely sensitive to the drug when hexokinase was present in the reaction medium . The sensitive site has been identified to lie in the region between the succinate dehydrogenase flavoprotein and ubiquinone of the respiratory chain.

Biochim Biophys Acta, 1983 Jan 12, 742(1), 184 - 8
Studies on the complex formed between bacitracin A and divalent cations; Scogin DA et al.; Bacitracin A is a peptide antibiotic which forms stoichiometric complexes with divalent cations, including Ni2+ and Zn2+ . In this paper it is shown that the metal-bacitracin complex contains a group which has a pKa near pH 5.5 . Deprotonation of the group is concomitant with the aggregation and precipitation of the metal-bacitracin complex . Bacitracin A, in the absence of metals, does not contain any group which has a pKa in this range . It is postulated that this group is the N-terminal amino of isoleucine, which was previously postulated not to be directly involved in metal coordination based on proton release measurements . An attempt was made to demonstrate directly that the N-terminal amino group is not coordinated to the metal by examining the reactivity of this group with 2,4,6-trinitrobenzene sulfonate . It was clearly shown that bound metals protect the N-terminal amino group from reacting with this reagent . It is speculated that this metal-protection results from a combination of factors, including steric hindrance.

Biochim Biophys Acta, 1983 Jan 5, 727(1), 108 - 14
Melittin and a chemically modified trichotoxin form alamethicin-type multi-state pores; Hanke W et al.; The bee venom constituent, melittin, is structurally and functionally related to alamethicin . By forming solvent-free planar bilayers of small area (approx . 100 microns 2) on the tip of fire-polished glass pipettes we could observe single melittin pores in these membranes . An increase in the applied voltage induced further non-integral conductance levels . This indicates that melittin forms multi-level pores similar to those formed by alamethicin . Trichotoxin A40, an antibiotic analogue of alamethicin, also induces a voltage-dependent bilayer conductivity, but no stable pore states are resolved . However, chemical modification of the C-terminal molecule part by introduction of a dansyl group leads to a steeper voltage-dependence and pore state stabilization . Comparing structure and activity of several natural and synthetic amphiphilic polypeptides, we conclude that a lipophilic, N-terminal alpha-helical part of adequate length (dipole moment) and a large enough hydrophilic, C-terminal region are sufficient prerequisites for voltage-dependent formation of multi-state pores.

Biochemistry, 1983 Jan 4, 22(1), 13 - 21
A rapid method for analysis of ligand binding to deoxyribonucleic acid and soluble nucleoproteins using streptomycin: application to steroid receptor ligands; Spelsberg TC; A method is described which allows the rapid analysis of the binding of practically any molecules to DNA or to protein--DNA complexes (termed nucleoacidic protein or NAP) . The antibiotic streptomycin sulfate, a soluble aminoglycoside, is used to precipitate the DNA after the ligand binding . Comparison of different sources and commercial batches of the antibiotic is described . Optimal conditions for precipitating DNA or NAP and the application of this method to the binding of the chick oviduct progesterone receptor to soluble NAP are described . The streptomycin method can be used with DNA molecules whose size ranges from 750 base pairs to greater than 50 000 base pairs . The method works with a DNA or NAP from a variety of sources, including synthetic homo- or heteropolymers . The precipitation of DNA or NAP by streptomycin occurs rapidly and has minimal effects on the steroid receptor complex or binding of the steroid receptor to DNA or NAP . The requirements and limitations of the method as well as the optimal conditions for binding of the progesterone receptor to DNA or NAP are described.

Digestion, 1983, 27(1), 36 - 43
Regulation of gastric mucosal DNA synthesis during fasting and refeeding in rats; Majumdar AP; The effects of 1-4 days of fasting and 3-24 h of refeeding of 4-day fasted rats on the rate of {3H}-thymidine incorporation into DNA in vitro (referred to as DNA synthesis) and the activity of thymidine kinase and DNA polymerase were measured in the oxyntic gland mucosa . Ad libitum fed rats served as control . Starvation for 1-4 days significantly depressed the activity of mucosal thymidine kinase (39-58%) and DNA polymerase (26-36%), when compared with the initially fed control . Mucosal DNA synthesis, measured in 3- and 4-day fasted rats, was also markedly decreased (80-90%) compared to the fed control . Refeeding of 4-day fasted rats significantly stimulated DNA synthesis and the activity of thymidine kinase and DNA polymerase . However, whereas DNA polymerase and thymidine kinase attained their respective peak activity (84 and 340% above the 4-day fasted level) after 3 and 6 h of refeeding, DNA synthesis was significantly stimulated (700% above the 4-day fasted control) after 9 h of refeeding . Administration of actinomycin-D prior to refeeding reduced the magnitude of stimulation of mucosal thymidine kinase and the rate of DNA synthesis, but had no effect on DNA polymerase activity which was found to be stimulated to the level of non-antibiotic treated rats . The current results demonstrate that following refeeding mucosal DNA polymerase and thymidine kinase activities are increased before DNA synthesis is significantly stimulated . Blocking of the maximal stimulation of mucosal thymidine kinase lowers the magnitude of the subsequent rise in DNA synthesis caused by refeeding.

Digestion, 1983, 26(4), 236 - 8
Factors preceding relapse of ulcerative colitis; Isgar B et al.; The effect of intercurrent diarrhoea on relapse of ulcerative colitis was investigated . Diarrhoea resulting from travel abroad, gastroenteritis or antibiotic usage resulted in an approximately 50% relapse rate . With regard to colonoscopy and barium enema, only the latter was followed by relapse and this may reflect differences in the preparation for the procedure.

Ann Biol Clin (Paris), 1983, 41(1), 13 - 6
{Comparison of the results of antibiograms obtained from blood culture broth and after isolation on agar media with the Autobac 1}; Flandrois JP et al.; The authors compare the results of antibiotic sensitivity tests performed within 4 hours with the aid of the Autobac 1 machine, using blood culture medium and following isolation on agar plates . There was concordance in about 90 p . cent of cases . The first test is not suitable for sensitivity to trimethoprim and the beta-lactamines, as was already observed in the study using the MS-2 machine . The authors discuss the various sources of error and compare the results obtained from the two machines.

Wien Med Wochenschr, 1983, 133(7), 183 - 7
{Pilot studies with aclacinomycin in patients with breast cancer or gastrointestinal tumors}; Rainer H et al.; Aclacinomycin (ACM), a new anthracycline antibiotic compound, was given intravenously q x 3 to 6 weeks in a dosage of 4 x 60 mg/4 days to 10 patients with metastasizing breast cancer and 5 patients with gastric carcinoma . Breast cancer patients, prior to ACM had extensive cytotoxic and hormonal treatments, gastric cancer patients received ACM as a first chemotherapeutic tumor treatment . No life-threatening hematologic toxicities could be noticed . All patients experienced moderate to severe gastrointestinal toxicities . No patient had considerable hair loss . 4 patients showed clinical signs of cardiac dysfunction: 1 ECG changes, 4 developed edema of lower extremities, 2 developed pericardial effusion . Moreover, 1 patient developed significant elevation of the pulmonary capillary wedge pressure (PCW) and prolongation of the systolic time intervals indicating pulmonary congestion grade I to II (Braunwald) . No significant increase in heart volume was registered . Clear signs of cardiotoxicity could be demonstrated in patients pretreated with adriamycin exclusively . In animal experience, ACM had been reported as less cardiotoxic as compared to adriamycin . Present studies seem to indicate ACM being considerably cardiotoxic at relatively low cumulative dosages . Among the 15 patients there was one with metastatic breast cancer pretreated with adriamycin and resistant to that drug in whom partial remission was achieved . The other patients did not objectively respond to ACM therapy . 3 out of 5 patients with gastric cancer had stabilisation of the disease but no objective response.

Mol Pharmacol, 1983 Jan, 23(1), 133 - 40
Correlation of structure and activity in ansamycins . Molecular structure of sodium rifamycin SV; Arora SK; The crystal and molecular structure of the sodium salt of rifamycin SV (clinically known as rifacin) as the monohydrate ethanol solvate has been determined to study the conformation of the ansa chain in unsubstituted rifamycins and also to clarify the metal complexation with rifamycins . The crystals belong to the space group P2(1)2(1)2(1) with cell dimensions (estimated standard deviations in parentheses) of a = 12.061 (2), b = 13.936 (2), and c = 24.731 (4) A . The structure was solved by direct methods and refined to an R factor of 0.069 . The conformation of the ansa chain differs from that of other active rifamycins, e.g., rifampcin and rifamycin B at the joining point of the ansa chain to the naphthohydroquinone chromophore . The conformation of the middle part of the ansa chain, which is essential for activity against DNA-dependent RNA polymerase, remains the same . The sodium ion is penta-coordinated and has a trigonal bipyramidal geometry . The intermolecular hydrogen bonding involves O(9), O(10), O(5), and O(6) through water and ethanol molecules . A two-step mode of action of rifamycins has been postulated, and the conformations of antibiotics suitable for penetration of the membrane barrier and that for antibiotic-enzyme complex formation have been suggested.

Ann Med Interne (Paris), 1983, 134(1), 51 - 4
{Gonococcal endocarditis . A new case}; Baudouy PY et al.; The authors report the case of a 35 year old female hospitalised for gonococcal endocarditis with mitral valve vegetations infecting pre-existing asymptomatic rheumatic mitral incompetence . Apyrexia was rapidly obtained with antibiotic therapy; the valvulopathy was well tolerated from the hemodynamic viewpoint; the echocardiographic appearances of the vegetations were stable . However, the patient died during the third week of a cerebral haemorrhage, probably due to rupture of a mycotic arterial aneurysm . The authors suggest that the difficulties encountered in the fight against sexually transmitted diseases may result in a recrudescence of this type of disseminated gonococcal infection.

Pathology, 1983 Jan, 15(1), 67 - 73
Histological assessment of orthotopic aortic valve leaflet allografts: its role in selecting graft pre-treatment; Armiger LC et al.; Histopathological studies of human cardiac valve grafts recovered at autopsy or re-operation, together with long-term clinical follow-up of valve graft recipients, have indicated that the success of grafts is largely dependent upon the extent to which they are replaced by host fibrous connective tissue . To find the valve preparation technique with least inhibitory effect on tissue ingrowth after grafting, various sterilizing and storage procedures were evaluated using a series of aortic valve leaflet allografts in dogs . To facilitate evaluation, a method for rapidly assaying relative degrees of colonization of grafts was first devised . Application of this method has unequivocally identified a newly-formulated antibiotic solution as the pre-treatment most compatible with host tissue ingrowth.

J Nat Prod, 1983 Jan, 46(1), 108 - 11
Non-competitive inhibition of hepatic and intestinal aryl hydrocarbon hydroxylase activities from rats by rifampin; Wu CL et al.; Rifampin is a semisynthetic antibiotic which is known to alter hepatic cytochrome P-450 mediated drug metabolizing enzymes . Using benzo(a)pyrene as the substrate we have shown that rifampin acts as a non-competitive inhibitor of hepatic microsomal aryl hydrocarbon hydroxylase in vitro at or below 0.10 mM and that it is also a non-competitive inhibitor of intestinal aryl hydrocarbon hydroxylase at or below 0.075 mM . These results suggest that the administration of rifampin with other drugs may result in altered drug biotransformation.

Clin Ther, 1983, 5(3), 279 - 83
Cyclacillin in the treatment of acute sinus infections and exacerbations of chronic infections; Ordonez FH; Cyclacillin was used to treat 40 patients with bacterial sinus infections, either acute or exacerbations of chronic infections . The drug was administered orally in a dosage of 500 mg every six hours for ten days, although three patients required extended treatment . More than 70% of the patients had remission of symptoms in six days, and all but the aforementioned three had remission in ten days or less . More than 90% of the patients had a moderate to good response; only two patients had a poor response . The only side effects were gastrointestinal disorders, which disappeared with administration of antacids . No side effects were noted in 72.5% of patients . Cyclacillin proved to be an effective and well-tolerated antibiotic for infections of the paranasal cavities.

Cancer Biochem Biophys, 1983, 6(3), 137 - 42
Evidence for the lack of relationship between inhibition of nucleic acid synthesis and cytotoxicity of adriamycin; Siegfried JM et al.; The ability of adriamycin-sensitive and -resistant Sarcoma 180 cells to incorporate thymidine and uridine into macromolecular material following exposure to this antibiotic was directly compared to the degree of cell survival by measuring in the same population precursor incorporation and cloning efficiency in soft agar after different intensities of drug exposure . The concentration and time dependence of inhibition of these processes by adriamycin wer compared . No correlation between the ability to incorporate radioactive precursors into DNA and RNA and the extent of cell survival was observed except ay very toxic drug concentrations . The results indicate that the extent of inhibition of precursor incorporation into DNA and RNA following drug exposure is not predictive of cell survival . This finding implies that the effect of adriamycin on nucleic acid synthesis is not directly coupled to cytotoxicity.

Crit Care Med, 1983 Jan, 11(1), 10 - 2
Selection criteria for pediatric critical care transport teams; Smith DF et al.; The primary goal of an interhospital critical care transport program is to provide quality medical care during transit as close as possible to that available in the receiving ICU . Critically ill pediatric patients are transported between hospitals by a variety of transport teams . The skills possessed by physicians, nurses, respiratory therapists, and paramedics overlap . To determine the criteria for selection of the team members for these patients, we reviewed the medical records of 115 pediatric patients transported to this facility in 1978 and 1979 . Patients were categorized by diagnosis, severity of illness at the time of transport, and the monitoring and life support required during transport . Our data indicate the medical transport team members should have skills required for pediatric critical care diagnosis and management including endotracheal intubation and assisted ventilation; insertion of peripheral, central venous, and arterial catheters; fluid and electrolyte therapy; antibiotic therapy; cardiovascular monitoring; and pharmacological life support . The team members should be chosen based on the particular skills needed for a transport with a goal of providing the patient care required on a consistent basis.

Z Naturforsch {C}, 1983 Jan-Feb, 38(1-2), 67 - 73
Sensitive fluorimetric assay for adenosine deaminase with formycin as substrate; and substrate and inhibitor properties of some pyrazolopyrimidine and related analogues; Wierzchowski J et al.; The nucleoside antibiotic formycin, 7-amino-3-(beta-D-ribofuranosyl)pyrazolo(4,3-d)pyrimidine, a structural analogue of adenosine, is deaminated about 10-fold faster by adenosine deaminase than adenosine itself, and is therefore a superior substrate for both routine assays and kinetic studies with the purified enzyme . The luminescence properties of formycin have been profited from to develop a fluorimetric assay for adenosine deaminase which is considerably more sensitive than the spectrophotometric procedure widely employed with adenosine as substrate . Examples are presented of its application to routine assays of adenosine deaminase levels in cellular extracts, as well as to kinetic studies with the purified enzyme, including the properties of some pyrazolopyrimidine and purine substrates and inhibitors.

Gerontology, 1983, 29(2), 89 - 96
Genetic effects on the longevity of cultured human fibroblasts . III . Correlations with altered glucose-6-phosphate dehydrogenase; Holliday R et al.; The level of heat-labile glucose-6-phosphate dehydrogenase (G6PD) has been measured in skin fibroblast cultures from premature ageing or DNA repair deficient genetic syndromes . The short in vitro longevity of Werner's syndrome, progeria, Cockayne's syndrome, ataxia telangiectasia, Fanconi's anaemia, and Bloom's syndrome cultures was correlated with the appearance of a significant fraction of heat-labile enzyme . Long-lived control cultures contain a low level of altered enzyme until they become senescent . The evidence that heat-labile G6PD molecules are derived from errors in synthesis, or from other causes, is critically assessed . It is shown that normal cells grown in medium containing the antibiotic, paromomycin, which is known to reduce the fidelity of ribosomal translation, produce a significant fraction of altered G6PD.

Dev Pharmacol Ther, 1983, 6(1), 55 - 63
Age-related effect of cycloheximide on lipid peroxidation in rough and smooth microsomes of rat liver; Pushpendran CK et al.; Cycloheximide, at a nonlethal dose of 2 mg/kg body weight, has different effects on microsomal in vivo lipid peroxidation in different age groups . In general, the antibiotic increases microsomal lipid peroxidation in newborn and 1-year-old rats, but decreases it in 15- and 75-day-old rats . Low doses of cycloheximide induces lipid peroxidation in vitro whereas higher doses cause inhibition . The degree of change differs in the two microsomal fractions . The sucklings are more susceptible to such a change than the older rats . In vivo lipid peroxidation in rat liver homogenate and rough and smooth microsomes declines as a function of age . Smooth microsomes show more lipid peroxidation than the rough in the different age groups.

Eur J Clin Pharmacol, 1983, 24(1), 109 - 12
Elimination of cefroxadine (CGP-9000) from patients undergoing dialysis; Nieto MJ et al.; The pharmacokinetics of cefroxadine was studied in 17 patients with terminal renal impairment, 10 of whom were undergoing 5 h dialysis sessions . The antibiotic was administered as a single oral dose of 500 mg . Cefroxadine followed a single compartment open kinetic model . During the interdialysis period in patients with terminal renal impairment, an average Cmax of 26.59 micrograms/ml and a tmax of 3.65 h were reached, which are greater than in patients with normal renal function . The serum half-life was reduced from 23.55 h in the interdialysis periods to 3.40 h during the dialysis sessions . The average extraction coefficient was 0.249 . It is recommended that a 500 mg dose cefroxadine should be administered at the end of each dialysis session if the interdialysis period is 48 h.

Arch Biochem Biophys, 1983 Jan, 220(1), 39 - 45
Purification and characterization of beta-ketoacyl-ACP synthetase I from Spinacia oleracea leaves; Shimakata T et al.; beta-Ketoacyl-acyl carrier protein (ACP) synthetase I was purified 180-fold from crude extracts of spinach leaves . The purified preparation was completely free from other component enzymes of the de novo fatty acid synthetase (FAS) system . Its molecular weight was estimated to be 56,000 by gel filtration . The apparent Km value for malonyl-CoA in the presence of ACP and malonyl-CoA:ACP transacylase was 4 microM . Purified synthetase I was highly active with acyl-ACP having chain lengths from C2 to C14, with hexanoyl-ACP being the most effective substrate, but palmitoyl-ACP was far less effective and stearoyl-ACP almost inactive . The antibiotic, cerulenin, strongly inhibited synthetase I activity . The inhibition by cerulenin was protected by prior incubation with hexanoyl-ACP, decanoyl-ACP, and myristoyl-ACP . The synthetase was inhibited by 1 mM p-CMB and 5 mM NEM, but not by 1 mM arsenite.

Antimicrob Agents Chemother, 1983 Jan, 23(1), 59 - 62
Nafcillin-induced platelet dysfunction and bleeding; Alexander DP et al.; This paper describes two cases of nafcillin-induced platelet dysfunction, with positive rechallenge data for one patient . Nafcillin resulted in abnormal bleeding times in both patients and a clinically apparent bleeding episode in one of the cases . Platelet function tests were performed on one patient during the initial therapy and after rechallenge with nafcillin . Platelet aggregation showed abnormal responses to ADP, collagen, and epinephrine . Platelet count and morphology were normal . Nafcillin should be recognized as another antibiotic which causes platelet function abnormalities and clinical bleeding episodes.

J Med Chem, 1983 Jan, 26(1), 25 - 9
Pyrrolopyrimidine nucleosides . 18 . Synthesis and chemotherapeutic activity of 4-amino-7-(3-deoxy-beta-D-ribofuranosyl)pyrrolo{2,3-d} pyrimidine-5-carboxamide (3'-deoxysangivamycin) and 4-amino-7-(2-deoxy-beta-D-ribofuranosyl)pyrrolo{2,3-d} pyrimidine-5-carboxamide (2'-deoxysangivamycin); Maruyama T et al.; A multistep synthesis, using the nucleoside antibiotic toyocamycin as the starting material, has furnished 6,2'-S-cyclosangivamycin (6) . Desulfurization of 6,2'-S-cyclosangivamycin (6) with Raney nickel has provided 2'-deoxysangivamycin (7) . Treatment of sangivamycin (1c) with sodium iodide and alpha-acetoxyisobutyryl chloride has furnished 4-amino-7-{2-O-acetyl-3-deoxy-3-iodo-5-O-(2,5,5-trimethyl-4-oxo-1, 3-dioxolan-2-yl)-beta-D-xylofuranosyl}-pyrrolo{2,3-d} pyrimidine-5-carboxamide (8a) . Dehalogenation of 8a with 10% palladium on charcoal was followed by a removal of the blocking groups with ammonium hydroxide to give 3'-deoxysangivamycin (9) in 49% overall yield . The reaction of sangivamycin (1c) with diphenyl disulfide and tributylphosphine gave 5'-(phenylthio)-5'-deoxysangivamycin (10) . Treatment of 10 with Raney Nickel afforded 5'-deoxysangivamycin (11) . Antitumor evaluation showed that 3'-deoxysangivamycin had significant activity against the murine leukemia L1210 both in vivo and in vitro, although it was less potent on a molar basis than the parent compound sangivamycin . The 2'- and 5'-deoxysangivamycins did not show significant antitumor activity.

J Med Chem, 1983 Jan, 26(1), 11 - 5
Adriamycin analogues . Preparation and biological evaluation of some novel 14-thiaadriamycins; Seshadri R et al.; Condensation of 14-bromodaunorubicin with thiols in methanol, in the presence of potassium carbonate, resulted in the formation of 14-thia analogues of the antitumor antibiotic adriamycin . However, similar condensation of N-(trifluoroacetyl)-14-iododaunorubicin with thiols invariably led to a redox reaction, with the formation of N-(trifluoroacetyl)daunorubicin and disulfides . Accordingly, N-(trifluoroacetyl)-14-bromodaunorubicin was used for reaction with thiols to yield thia analogues of the clinically active but non-DNA-binding adriamycin analogue N-(trifluoroacetyl)adriamycin 14-valerate (AD 32) . Reaction of 14-bromoadunorubicin with alpha, omega-alkanedithiols gave bis(thiaadriamycin) analogues as potential difunctional intercalating agents . The aforementioned products, plus two related phenylselena derivatives, were examined for in vitro growth inhibition, in vivo antitumor activity, and, where appropriate, DNA binding . A number of agents, most notably 14-(carbethoxymethyl)-14-thiaadriamycin and N-(trifluoroacetyl)-14-phenyl-14-selenaadriamycin, were active against murine L1210 leukemia in vivo . Several of the amino glycoside unsubstituted 14-thiaadriamycin analogues exhibited DNA-binding properties equivalent to those of adriamycin.

Am J Vet Res, 1983 Jan, 44(1), 68 - 71
Absorption in calves of amoxicillin, ampicillin, and oxytetracycline given in milk replacer, water, or an oral rehydration formulation; Palmer GH et al.; Oxytetracycline, amoxicillin or ampicillin suspended in milk replacer, water, or a glucose-glycine-electrolyte solution (GGES) was orally given to calves (n = 64) . Oxytetracycline suspended in milk replacer gave lower relative bioavailability than when suspended in water (P less than 0.01) or in GGES (P less than 0.001) . Seemingly, the 63% binding (only partly reversible) of oxytetracycline suspended in milk replacer was responsible for low serum concentrations, whereas the greater water absorption from the GGES was responsible for improved uptake of antibiotic . Amoxicillin suspended in milk replacer had a delayed absorption, compared with that suspended in water, but the relative bioavailabilities from milk replacer and water were similar . In contrast, peak serum concentration and bioavailability were higher (P less than 0.05) when amoxicillin was suspended in GGES than when suspended in water . Binding of amoxicillin with milk replacer was comparatively low (16%) and was reversible . Ampicillin suspended in GGES gave a higher peak serum concentration (P less than 0.05) than when suspended in milk replacer . It, therefore, appeared that these antibiotics were more bioavailable when suspended in GGES than when suspended in water or especially in milk replacer . Oxytetracycline was bound particularly strongly to milk replacer.

Lab Invest, 1983 Jan, 48(1), 80 - 9
Distribution of filipin-sterol complexes in plasma membranes of the kidney . II . The thin limbs of Henle's loop; Orci L et al.; Thin limbs of Henle from the rat kidney were investigated by freeze fracture electron microscopy after incubation of the tissue with the polyene antibiotic, filipin, a morphologic probe for membrane cholesterol . Distinct patterns of distribution of filipin-sterol complexes were found in plasma membranes of epithelial cells from each of the four thin limb regions examined . In particular, adjacent cells in the thin ascending limb had either heavily or poorly labeled apical membranes, whereas in the lower part of long descending thin limbs, all apical membranes were poorly labeled . In contrast, both apical and basolateral membranes of short descending limbs were heavily labeled with filipin-sterol complexes . These results demonstrate the existence of plasma membranes with different properties both within specific segments of Henle's loop (ascending thin limb) and between different thin limb segments (short and long descending limbs).

Dis Colon Rectum, 1983 Jan, 26(1), 59 - 60
Diverticulitis of the midrectum; Chiu TC et al.; Diverticulitis of the rectum is a rare condition . This report covers patient history, diagnosis, and treatment involved in such a case . The patient presented with a history of rectal pain and muscle spasm of six months' duration . After several available examinations had been completed, i.e., digital examination, sigmoidoscopy, and barium-enema examination, the diagnosis of a rectal diverticulum was made . Initially, conservative treatment, including high-fiber diet and sitz baths, proved effective . Approximately nine months later, the patient developed severe rectal pain, unrelieved by previously effective measures . After the above-described examinations had been repeated, the rectal wall was found to be ulcerated and inflamed, and a diagnosis of diverticulitis of the rectum was made . Antibiotic therapy and evacuation of the 3- to 4-cm mass under anesthesia resulted in subsidence of symptoms and resolution of the mass . Segmental resection will be considered if the diverticulum becomes infected again.

Rev Fr Mal Respir, 1983, 11(6), 907 - 13
{Mycotic aneurysms of the intrapulmonary arteries: unusual manifestation of right-sided endocarditis}; Godin N et al.; We report the case of a 27 year old man admitted to hospital for investigation of radiological opacities of recent origin . A diagnosis of mycotic aneurysms was made on a surgical biopsy . Although a right sided endocarditis could not be detected clinically, a trial of antibiotic therapy was instituted . However, no improvement occurred . The patient died, following a massive pulmonary haemorrhage . The necropsy revealed an active right sided endocarditis with multiple aneurysms of the intra-pulmonary arteries.

Eur J Drug Metab Pharmacokinet, 1983, 8(1), 43 - 9
Pharmacokinetic study of doxycycline polyphosphate+ after simultaneous ingestion of milk; Saux MC et al.; Pharmacokinetic parameters of doxycycline polyphosphate were studied in healthy volunteers after oral administration of a single 200 mg dose of this antibiotic with a breakfast containing or not 200 ml of whole milk . Ingestion of milk had only mild effect upon absorption parameters of doxycycline; only a moderate increase of the lag-time was significant . Elimination parameters of doxycycline were impaired by milk; a decrease of the terminal half-life from 28 h to 15 h, and apparent decrease of the enterohepatic circulation and an increase in total body clearance from 40 to 62 ml/min . were observed.

J Emerg Med, 1983, 1(2), 133 - 6
Fournier's disease: necrotizing gangrene of the male genitalia; Mabry RM et al.; Fournier's disease, a necrotizing subcutaneous infection involving the male genitalia, was first described by the French venereologist Jean Alfred Fournier in 1884 . Its characteristic triad of abrupt onset in young, previously healthy males, rapid progression to gangrene, and absence of a discernable cause appear to have been altered, at least partially, by the advent of the antibiotic era . We present a case report, with discussion of the clinical and pathophysiological mechanisms involved in this rare and malignant infectious process.

Invest New Drugs, 1983, 1(3), 249 - 51
The treatment of acute leukemia with continuous infusion L-Alanosine; Weick JK et al.; L-Alanosine, an antitumor antibiotic was administered by members of the Southwest Oncology Group (SWOG) to 22 patients with resistant acute non-lymphocytic leukemia . The drug was administered by continuous infusion for five days at a starting dose of 125 mg/m2/day . Mucositis was dose-limiting in 15 patients and no marrow aplasia was attained . As administered, L-Alanosine is not an effective single agent in acute leukemia.

Haemostasis, 1983, 13(6), 385 - 93
Diminished osmotic and chemically induced haemolysis of human erythrocytes following exposure to contrast media molecules; Paul J et al.; Radiocontrast molecules (RCM) used in coronaroangiography and/or urography diminished their osmotic fragility when they were incubated for 30 min with human erythrocytes . The shift of the osmotic fragility curve towards lower NaCl concentration is related to the hypertonicity of RCM, but in addition, at a given osmolality (100 +/- 5 mosm/kg), RCM at the concentration of 4-10% v/v increase the resistance to osmotic lysis or even suppress it . Similar protection is observed towards erythrocyte lysis induced by a detergent (saponin), polyenic antibiotic (filipin) or non-polyenic cholesterol-specific agent (digitonin) . The effect is (1) proportional to the amount of RCM present, (2) independent of hypertonicity of the molecule, and (3) related to the nature of acidic molecules . A weak insertion of RCM into the erythrocyte membrane is suggested since it was suppressed by a single washing of the cells.

Nucleic Acids Symp Ser, 1983, (12), 119 - 22
Inhibition of S-adenosylhomocysteine hydrolase by purine nucleoside analogues; Ishikura T et al.; To find out potent inhibitors of S-adenosylhomocysteine hydrolase (SAHase), several deazaadenosine analogues synthesized in this laboratory and some naturally occurring nucleoside analogues were examined with SAHases from yellow lupin seeds and rabbit liver . Neplanocin A, an antibiotic, inhibited both enzymes more potently than aristeromycin which was also an antibiotic and known as one of the most potent inhibitors of SAHase . The 3-deazaadenine derivatives (2'-deoxy, arabinosyl, xylosyl) inactivated lupin SAHase as potent as 3-deazaadenosine . Whereas, inhibitory activities of 1-deazaadenosine, its derivatives, and 7-deazaadenosine (tubercidin) were very weak.

Acta Otorhinolaryngol Belg, 1983, 37(4), 624 - 34
Surgical treatment of sinusitis; Hellmich S; There is no doubt that there is a considerable number of cases of acute and chronic sinusitis, which can be cured only by surgical intervention . The modern philosophy should be: to choose a surgical technique as conservative as possible and as radical as necessary according to the individual case . To achieve this goal, an exact knowledge of the anatomy and pathology of the paranasal sinuses, as well as a full command of the available diagnostic methods (including sinuscopy) are essential . The sometimes dangerous complications of acute ethmoiditis in children usually can be solved by simple displacement of the middle turbinate to the center and uncapping of the ethmoidal cells assisted by antibiotic and antiphlogistic treatment . The surgical treatment of choice in cases of acute recurrent or chronic maxillary sinusitis in children (often combined with bronchial or allergic problems) is the installation of a nasoantral window from the inferior meatus, to guarantee adequate drainage . In adults, the radical techniques of Caldwell-Luc (maxillary sinus) and Riedel (frontan sinus) should be used in selected cases only . They should be replaced--if possible--by osteoplastic methods or modified techniques (frontal and maxillary sinus) or bimeatal-transnasal approach under endoscopic control (maxillary and ethmoidal sinus) . Healthy and reversibly damaged mucosa should be saved; but at the cost of sacrificing the nasal function instead.

Acta Neuropathol (Berl), 1983, 61(3-4), 291 - 9
Toxic effects of adriamycin on the central nervous system . Ultrastructural changes in some circumventricular organs of the mouse after intravenous administration of the drug; Bigotte L et al.; Recent experimental studies have shown that the cytotoxic antibiotic adriamycin (doxorubicin) after systemic administration can enter the so-called circumventricular organs (CVO) of the brain of the mouse . The present experiments were performed to find out whether such penetration of the brain is associated with signs of neurotoxic injury . For this purpose, light- and electron-microscopic observations were carried out on three of these organs: the neurohypophysis (NH), median eminence (ME), and postremal area (PA) . Pronounced widening of the extracellular space indicating the presence of edema was present in all the regions, particularly in animals examined within 3 days of injection of the drug . Many degenerated axon terminals were observed in the NH and ME . The glial cells within these regions showed rarefaction of the nuclear chromatin, nucleolar segregation, and also cytoplasmic changes . The PA presented marked cellular changes resulting in degeneration of neurons, which was most evident 30 days after the injection . Hence, regions of the CNS outside the blood-brain barrier can be reached by adriamycin after systemic administration, and the drug can induce morphological changes there . The doses of the drug used in the present experiments were comparable to those given to patients for the treatment of malignant tumors.

Neurochirurgie, 1983, 29(4), 229 - 33
{Analysis of infectious sequelae of 1000 neurosurgical operations . Effects of prophylactic antibiotherapy}; Raggueneau JL et al.; Postoperative infections: cellulitis at the site of skin incision and/or meningitis, were reported in 5.1 p . cent of 1 000 cases treated by neurosurgery in Pr R . Houdart's department between december 1980 and march 1982 . Statistically significant factors predisposing to infection were: emergency surgery, opening of the sinus, presence of a foreign body, and operation lasting more than 5 hours . The age of the patient, diabetes, or previous corticoid therapy did not significantly alter the risk of infection . Prophylactic antibiotic therapy had been administered to 37 p . cent of patients, but this had not affected the incidence of general infection, a statistically significant effect being observed only after operations lasting for more than 5 hours . The risk of infection was high after craniotomies and major after external ventricular shunts (valves) . For the latter type of operation it was not possible to determine factors favorable for infection: neither duration of surgery, nor age of patient, nor absence of antibiotic therapy . The risk of postoperative infection was low (less than 1 p . cent) in the absence of factors favorable for its development, but its frequency increased considerably in patients presenting one or more other intercurrent infections . It is therefore possible to recognize surgical and general factors influencing infection, but prophylactic antibiotic therapy has only a weak effect on morbidity modification.

Intervirology, 1983, 20(2-3), 101 - 7
Biogenesis of vaccinia: analysis by three-factor crosses reveals mutual influence on stability of drug resistance and temperature sensitivity when both markers occur in some recombinant virus isolates; Essani K et al.; Recombination analysis with 5 temperature-sensitive (ts) mutants of vaccinia virus, relegated to the E category phenotype and mimicking closely the effects produced by the antibiotic rifampicin, was undertaken to determine whether the genetic loci determining this phenotype were clustered on the genetic map . Optimum conditions for analysis were established with respect to the MOI and duration of incubation . At an MOI of 5-10, consistent values of recombination frequency (RF) were obtained, but became significantly lower when the MOI was 1 or less . Constant RF values were recorded when the duration of the infection was 8-24 h . These values were increased 3-fold by extending the incubation to 36 h . Under the standard conditions for analysis adopted, each mutant partner was added at an MOI of 10 and incubation was for 18 h . The map of group E mutants drawn from RF values obtained by 2-factor crosses was confirmed by 3-factor cross analysis, in which recombinants carried both the ts mutations and the rifampicin-resistance (R) marker . Both 2- and 3-factor cross data revealed that the 5 group E mutations were not clustered on the vaccinia virus genome . Surprisingly, after recombining ts 7743 with rifampicin resistance (R), different isolates of ts 7743 R could be mapped at two loci to the right or left of another isolate, ts 9383 . Characterization of five independent plaque isolates of the progeny arising from a ts 7743 R parent showed that one isolate possessed a cold-sensitive phenotype (33 degrees/40 degrees = 1:26), two isolates retained their original ts character, and two became phenotypically like wild type (wt) with respect to thermosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Clin Pharmacol, 1983, 25(3), 333 - 8
The influence of uremia on the accessibility of phosphomycin into interstitial tissue fluid; Fernandez Lastra C et al.; The entry and persistence of phosphomycin in interstitial tissue fluid (ITF) were studied in 9 patients with normal renal function and 8 patients with varying degrees of renal impairment, all of whom received a single i.v . dose of 30 mg/kg . ITF was obtained from skin blisters produced by suction . The antibiotic followed a two-compartment open kinetic model . In patients with normal renal function, phosphomycin is incorporated rapidly into the ITF reaching a level of 60.4 micrograms/ml 60 min after administration . There was no statistically significant difference between the elimination rates from serum and ITF . The serum half-life of the slow disposition phase was 1.75 h in patients with normal renal function . There was a linear correlation between the elimination half-life of phosphomycin in serum and ITF in subjects with differing degrees of renal impairment.

Drug Chem Toxicol, 1983, 6(3), 267 - 77
Acute toxicity of some silver salts of sulfonamides in mice and the efficacy of penicillamine in silver; Horner HC et al.; The silver salt of 2-metanilamido-5-chloropyrimidine (AgMCP) and the sodium, amminosilver and trimethylphosphite-silver salts of 3',5'-dichlorobenzenesulfonanilide (NaDBS, AgNH3DBS and AgP(OCH3)3DBS were synthesized as possible antibiotic of antiparasitic drugs . All the organosilver compounds were extremely water-insoluble . For animal studies these, and other reference compounds, were given as fine suspensions in an Emulphor-safflower oil mixture . The ip LD50's in mice in mmol/kg were: 1.67 for NaDBS, 0.22 for silver acetate (AgAc), 0.15 for AgP(OCH3)3DBS, 0.13 for AgMCP and 0.10 for AgNH3DBS . When given by mouth, 15 mmol AgAc/kg produced a high mortality, but none of the organosilver compounds caused death in maximal doses (1.9 to 2.6 mmol/kg) that could be given based on considerations of total volume and stability of the suspension . All the silver compounds, including AgAc, produced a similar toxic syndrome with initial hyperexcitability, ataxia, central nervous depression, labored breathing, loss of righting reflex and death . Most deaths occurred between 12 and 24 hours after dosing . In contrast, animals given NaDBS often died within 3 hours although the major signs were very similar to those produced by the silver compounds . When given ip as a single dose 30 minutes after AgAc, D-penicillamine was effective in reducing mortality, but it had no effect on the mortality of the organosilver compounds . Histological studies revealed similar patterns of silver deposition, especially in the liver and kidneys, at 6, 18 and 24 hours after the organosilver compounds and after AgAc . We conclude that the presence of silver contributes significantly to the acute toxicity of these sulfonamides although they may dissociate free silver less readily than does AgAc.

Biol Res Pregnancy Perinatol, 1983, 4(3), 123 - 6
Gentamicin monitoring in low-birth-weight newborns; Rameis H et al.; The pharmacokinetics of gentamicin in premature newborns is influenced by many noncalculable variables . Nevertheless, and despite its narrow therapeutic range, this aminoglycoside antibiotic is usually prescribed according to a fixed schedule . Gentamicin was monitored in 22 severely sick, low-birth-weight newborns on combination therapy of various antibiotics including gentamicin . Dosage regimen of gentamicin was prescribed according to Eichenwald and McCracken {1978} . Serum gentamicin concentrations were measured by radioimmunoassay before infusion, 30 min after, and 3 h after infusion of the antibiotic . In 22 prematures desirable serum gentamicin concentrations with a mean elimination half-life (t 1/2) of 5.3 h; in 2 prematures, levels with a mean t 1/2 of 2.3 h; in 7 prematures, possible toxic levels with a mean t 1/2 of 8.3 h; and in 2 prematures, definite toxic levels with a prolonged t 1/2 up to 17 h were observed . Most of the prematures with possible or definite toxic gentamicin levels were not older than 1 week . This is explained by the immaturity of the kidneys and the retention of aminoglycosides . A satisfactory correlation between postnatal age and gentamicin elimination half-life was found, which might be caused by postnatal maturation of the glomerular function . In prematures in the 1st postnatal week we recommend reducing the daily dose by prolonging the dosage interval, e.g., from 12 to 18 h, or reducing the single gentamicin doses . Gentamicin monitoring seems advisable for detecting toxic serum concentrations and accumulation and for revealing an insufficient dosage of this aminoglycoside antibiotic.

Vet Med Nauki, 1983, 20(3-4), 47 - 51
{LDH activity and isoenzyme spectrum in the leukocytes of cows with catarrhal mastitis and chronic endometritis}; Deianov M; The activity of lactatedehydrogenase (LDH) in the leukocytes of cows affected with mastitis and endometritis was found to drop strongly to the detriment of the aerobic fractions of LDH1 and LDH2 . The processes of anaerobic glycolysis in such animals ran more intensely their course . The antibiotic therapy raised the functional activity of the white blood cells.

Vet Med Nauki, 1983, 20(3-4), 40 - 6
{Toxicity, tolerance and blood concentrations of iron and tylosin with the use of preparation FV-82}; Dilov P et al.; A pharmacologic evaluation was made of a technologic model of a liquid drug form (code name phi B-82), having the following composition: tylosine tartrate 3500000 UI, cyanocobalamine 0.008 g, pyridoxin hydrochloride 0.500 g, tartaric acid 0.100 g, and feridextran (dextrofer-100) up to 100 cm3; pH from 5.5 to 6.5, and Fe3+ 100 mg/cm3 . It was found that phi B-82 at i/m application to rabbits, subcutaneous injection to albino mice, and intra-abdominal introduction to albino rats and mice at rates that were equal to ED100 and 3 to 5 times higher than those used with pigs did not lead to local and total lack of tolerance . The acute toxicity (LD50) of phi B-82 at intra-abdominal application to 18-20 g albino mice was 29.2 cm3/kg . The single muscular application to guinea pigs at 2 cm3 per kg of body mass showed good absorption of the preparation - it did not differ essentially from those of dextrofer-100 and aquaous solution of tylosine tartrate used in equivalent amounts . The bacteriostatic concentrations of tylosine were maintained for 24 hours . It was shown that the optimal effect would be produced by a combined preparation having the qualities of the feridextrane complexes with a rapid absorption and those of the erythropoietic vitamins of the B12 group and B6 along with the participation of tylosine as an antibiotic.

J Foot Surg, 1983 Fall, 22(3), 212 - 7
Chronic osteomyelitis associated with monofilament wire fixation; Varzos PN et al.; Infections following osteotomy and internal fixation must be treated aggressively . The plan of treatment should include the following: 1) continued immobilization of the part during healing, 2) removal of any internal fixation device after the osteotomy site is stable, 3) debridement of necrotic debris, and 4) use of an appropriate antibiotic over a sufficient time period (including a few weeks after removal of an internal fixation device) . A report was made of a case of chronic osteomyelitis that may have resulted from undertreatment of a postoperative infection.

Zentralbl Chir, 1983, 108(11), 641 - 6
{Treatment and treatment results of infections of the hand with gentamicin PMMA minichains}; Asche G; Soft tissue and bone infections often require lengthy treatment . In most cases this will result in a poor function . The treatment can be shortened by surgical revision and highly effective local antibiotic therapy with Gentamycin-PMMA-minichains.

Biomed Biochim Acta, 1983, 42(2-3), 189 - 94
A three-stage chromatographic procedure for cordycepin . Quantitative estimation in rat brain tissue; Musaev NI et al.; A technique for the quantitative estimation of intraperitoneally injected unlabelled cordycepin in the acid soluble pool (ASP) isolated from rat brain tissue has been suggested . It consists of consecutive chromatography of ASP on columns of Dowex 1 X 8, Dihydroxyboryl-SP500 and Sephasorb-HP . As a result, the fraction containing 2'-deoxyriboadenosine and 3'-deoxyriboadenosine (cordycepin) was isolated from the brain tissue ASP of experimental animals which were given a cordycepin injection . The 2'-deoxyriboadenosine fraction was isolated from tissue ASP of control animals which were not given an injection of this antibiotic . Brain tissue antibiotic content was estimated by the difference in mumolar nucleosides quantity values in the two fractions (control/experiment).

Scand J Infect Dis Suppl, 1983, 41, 187 - 91
Intensive care treatment in septic shock; Lundberg D et al.; Deaths in septic shock continue to occur at a high frequency despite current treatment programs . However, the mortality can be substantially decreased with a close bedside attendance of patients at risk and if the patient is transferred to an intensive care unit for intensive treatment and monitoring as soon as shock is suspected or established . The treatment program consists of adequate antibiotic administration in combination with massive doses of steroids and aggressive infusion therapy supplemented with cardiovascular drugs according to the hemodynamic response to the initial treatment.

Mol Gen Genet, 1983, 192(3), 471 - 6
Possible plasmid involvement in turimycin production in Streptomyces hygroscopicus; Zippel M et al.; Streptomyces hygroscopicus JA 6599 is the producer of the macrolide antibiotic turimycin . Mapping analysis by conventional matings and protoplast fusion techniques were carried out . The sequence of auxotrophic markers determined by using the method of minimizing the frequency of quadruple crossover recombinants, could be shown to be in accordance with the related marker sequence of Streptomyces coelicolor after both conjugation and protoplast fusion . However, the tur locus could localized between chromosomal markers only assuming quadruple crossover . Moreover, after conventional crosses the tur marker has to be localized at quite another site than after protoplast fusion . Regarding also our results on the evidence of extrachromosomal DNA in strains of S . hygroscopicus, the following hypothesis is proposed: the structural genes for turimycin biosynthesis are localized on the bacterial genome, but plasmid-borne genes might be involved in the control of the antibiotic production in a yet unknown way, possibly by inducing chromosomal rearrangements.

Leuk Res, 1983, 7(1), 67 - 75
Recognition of drug resistance during remission induction therapy for acute non-lymphocytic leukemia: utility of day 6 bone marrow biopsy; Preisler H et al.; While the majority of patients under 70 years of age with acute non-lymphocytic leukemia enter remission when treated with a combination of cytosine arabinoside and an anthracycline antibiotic, 20-45% of patients do not . The reasons for treatment failure in these patients vary from drug resistant disease to death from infection or bleeding shortly after remission induction therapy is initiated . Clearly, more intensive remission induction therapy should be administered only to those patients for whom the therapy being employed is of insufficient intensity . Bone marrow biopsies after six days of therapy have been performed on 53 patients who received 65 courses of remission induction therapy . Eighty-eight per cent of the remissions occurred in patients whose marrow cellularity was less than 62.5% on day 6 while 78% of patients who had drug resistant disease had day 6 marrow cellularities which exceeded 62.5% . Hence, a bone marrow biopsy performed after six days of therapy permits the recognition of the majority of patients who will enter complete remission or alternatively who need more aggressive therapy.

J Cancer Res Clin Oncol, 1983, 105(2), 162 - 5
Phase II trial of aclacinomycin A in acute leukemia and various solid tumors; Schutte J et al.; Aclacinomycin A (ACM) is a new anthracycline antibiotic with a reduced cardiac toxicity in animal models . A phase II study was performed in a total of 25 patients, 23 of whom are evaluable for response . All suffered from recurrent and advanced tumors . Pretreatment consisted of at least four different chemotherapeutic agents (range: 4-9) . Lung cancer patients (3/9) were irradiated to the mediastinum . Eighteen patients were pretreated with doxo- or daunomycin . The dose for solid tumors was 2-3 mg/kg given on 3 consecutive days every 3 weeks . Leukemia patients received a daily dose of 20 mg/m2, and standard response criteria were used . Marked reductions of leukocyte counts were achieved in leukemia patients . The overall response rate was about 15% in solid tumors, but major objective responses (CR + PR) have not been observed . Myelosuppression was commonly moderate in solid tumor patients, nausea and vomiting were rare, and alopecia was not induced . Cumulative cardiotoxicity was not evaluated in this trial . Treatment with ACM requires further investigation in acute leukemias and solid tumors, not pretreated with anthracycline antibiotics.

Z Allg Mikrobiol, 1983, 23(6), 359 - 65
Effect of the autoregulator from Streptomyces griseus JA 5142 on surface cultures of blocked mutant ZIMET 43682; Grafe U et al.; Zero time addition of the autoregulator (L-factor) from S . griseus (Lkm+Amy+) to surface cultures of its bald mutant ZIMET 43 682 (Amy-Lkm-) restored the capacity to form both anthracycline-type antibiotic leukaemomycin and aerial mycelium . The pertinent mycelia displayed the same growth rate and cellular levels of nucleic acids as the asporogeneous phenotype but the composition of fatty acids and phospholipids as well as the ratio of cytochromes b and c were altered . These differences indicate alterations in the cellular architecture of substrate and aerial hyphae . The results suggest that the autoregulator triggers the onset of a complex programme of differentiation at a very early stage.

J Membr Biol, 1983, 74(2), 131 - 8
Ultrastructural characterization of cholesterol distribution in toad bladder using filipin; Stetson DL et al.; The polyene antibiotic filipin was used to characterize the cholesterol distribution in the membranes of the toad bladder epithelium in freeze-fracture replicas . The apical membranes of granular and mitochondria-rich cells incorporate moderate amounts of filipin while the basolateral membranes of both cell types incorporate substantially greater amounts . Intracellular membranes, in general, take up very little filipin . The major exception to this is the granule membrane, which appears to be rich in cholesterol . An inverse correlation was found between the density of filipin-sterol complexes in the apical membrane and the incidence of granules in the cytoplasm . This suggests that fusion of granules with the apical membrane may be responsible for variation in the concentration of cholesterol in the apical membrane . Thirty minutes following vasopressin exposure, there is no consistent change in the cholesterol content of the apical membrane of granular cells as measured by the incidence of filipin-sterol complexes . The lack of change in the amount of membrane cholesterol indicates that the vasopressin-induced increase in transepithelial water permeability is not mediated by a change in cholesterol content of the apical membrane.

Mol Immunol, 1983 Jan, 20(1), 89 - 99
Use of Trypanosoma equiperdum infected rabbits as a source of splenic mRNA; construction of cDNA clones and identification of a rabbit mu heavy chain clone; Bernstein KE et al.; Rabbits were infected by Trypanosoma equiperdum and the splenic mRNA was isolated . In vitro translation of this RNA and immunoprecipitation with anti-light chain, anti-heavy chain, anti-mu and anti-VH antibodies demonstrated that T . equiperdum infection elicits large quantities of splenic mRNA encoding mu and kappa chains . The mu and gamma heavy chains and the kappa light chains synthesized in the cell-free translation system were specifically immunoprecipitated by antisera to heavy chain VHa and light chain kappa b allotypes . In vitro labeling of spleen cells from trypanosome-infected animals demonstrated that the biosynthetically labeled IgM has a mu chain of higher molecular weight than the mu chain synthesized by in vitro translation, a difference that is largely abolished when cellular glycosylation is blocked with the antibiotic tunicamycin . Enrichment for heavy chain or light chain mRNA was achieved by fractionating mRNA from trypanosome-infected animals on a sucrose gradient . cDNA clones carrying mu heavy chain sequences were produced using a 'one tube' protocol and identified by cross species hybridization and hybridization selection . Infection of rabbits with T . equiperdum followed by sucrose gradient enrichment of splenic mRNA has provided sufficient quantities of mRNA encoding mu heavy chain suitable for cDNA cloning.

J Cancer Res Clin Oncol, 1983, 105(3), 250 - 7
Chemotherapeutic study on Yoshida sarcoma ascites cells implanted into the glandular stomach of rats . Monotherapy with 5-fluorouracil, methyl-CCNU, mitomycin C, adriamycin, and cytosine arabinoside, and combination therapy with respective two-drug combinations; Eichler G et al.; The chemotherapeutic activity of five cytostatic drugs was investigated experimentally in monotherapy and in two-drug combinations, using Yoshida sarcoma cells implanted into the wall of the glandular stomach of Sprague-Dawley rats . In monotherapy, the antibiotic agent mitomycin C and the nitrosourea methyl-CCNU exhibited the highest cytotoxic activity in this tumor model . In combination therapy, the combination of these two drugs was superior to all the other therapeutic schemes tested . In general, the results demonstrate a marked superiority of combination therapy in comparison with monotherapy.

Arch Mal Coeur Vaiss, 1983 Jan, 76(1), 53 - 60
{Reoperations on heart valve prostheses . Apropos of 58 cases}; Ben Ismail M et al.; In the period from 1968 to November 1980, 1 023 patients underwent surgery for single or multiple valve replacement . Fifty three patients (6,6% of the follow-up population) had to be reoperated, including 5 patients who had to be reoperated twice, giving a total of 58 reoperations . The average interval before reoperation was 30 months . The incidence was similar in monovalvular (7,5 p . 100 mitral valves, 5 p . 100 aortic valves) and polyvalvular (7 p . 100) cases . On the other hand, the incidence of reoperation of tricuspid prostheses (17 p . 100) was significantly superior to that of mitral valve (5,3 p . 100) or aortic valve (3,8 p . 100) prostheses . In 91 p . 100 of cases, the indication for reoperation was prosthetic valve dysfunction related to endocarditis in over a third of cases (21) . In 32 cases, reoperation was required in the absence of any infectious process: 13 spontaneous perivalvular leaks, 10 thromboses, and 9 stenosing prostheses . There were no reoperations for wear of the prosthetic material . Only 9 p . 100 of patients were reoperated for uncorrected valvular disease . The prognosis of these reoperations was poor; hospital mortality being 42,5 p . 100 . This high mortality rate is explained by the frequency of reoperation for infective endocarditis (36 p . 100) in our series, the mortality of which was 73,6 p . 100 and even higher when reoperation was an emergency for infectious or hemodynamic reasons . There was also a high mortality rate with reoperation for thrombosis (30 p . 100) because of the severe myocardial dysfunction in thrombosis of tricuspid prostheses and the emergency situation associated with mitral prosthetic valve thrombosis . Excluding these two complications, the average mortality was 21 p . 100 . Although the surgical indications are relatively easy for thrombosis, perivalvular leak and stenosing prostheses, they are particularly difficult in infectious endocarditis especially with regards to the timing of reoperation . We believe that, ideally, reoperation should be delayed as long as possible to allow the antibiotic therapy the maximum time to take effect . Surgery can then be performed after controlling the infection and before the installation of severe hemodynamic distress.

Z Orthop Ihre Grenzgeb, 1983 Jan-Feb, 121(1), 6 - 9
{Azlocillin--synovial fluid levels after intravenous doses}; Harle A et al.; The corresponding levels of azlocillin in serum and in synovial fluid in the knee-joint were investigated in patients who had undergone aseptic surgery of the lower limbs . The mean synovial fluid concentrations for azlocillin were determined on the basis of 30 samples . Clinically relevant azlocillin levels of approximately 40 mu g/ml were recorded in synovial fluid 10 minutes after start of a short infusion of 5 gm . These increased until about 90 minutes after commencement of antibiotic administration when the maximum level was attained . Subsequently synovial fluid levels decreased slowly and approximately 170 minutes after commencement of the short infusion the mean for serum and synovial concentrations corresponded . The results confirm that with an i.v . infusion of 5 g azlocillin levels can be attained for 3 hours in the synovial fluid that are above the break-point for this antibiotic of 64 mu g/ml . However, despite these good pharmacokinetic data it should be remembered that experience has shown that surgical reintervention is often necessary in addition in joint infections to achieve ultimate cure.

Rev Argent Microbiol, 1983, 15(2), 95 - 104
{Production and properties of the milk-clotting enzyme}; Bernardinelli SE et al.; Milk-clotting enzyme from a strain of Mucor varians Pispek selected in a previous work was obtained by solid culture followed by water extraction . Moistened wheat bran (120% water on dry bases) proved to be a good medium for the production of the milk-clotting enzyme . The production may be related to growth and 4,000 U milk-clotting activity by g of wheat bran was achieved . The milk-clotting enzyme was easily extracted with water from the cultures and could be precipitated by salting out with ammonium sulfate or by mixing with ethanol, methanol or acetone . The crude enzyme is an acid protease having optimal activity at pH: 3.0 . Like calf rennet, this crude enzyme from M . varians loses activity with heat treatment . The level of lipolytic activity of the crude enzyme is similar to some commercial preparations and neither an antibiotic nor an amylase activity was demonstrated in the crude extracts.

Symp Fundam Cancer Res, 1983, 36, 133 - 43
Tumor cell hybridization and neoplastic progression; Hart IR; In the experiments reported here, I was unable to detect any fusion between host cells and transplanted tumor cells; however, spontaneous hybridization between tumor cells appears to occur in the B16 melanoma . This hybridization was demonstrated by mixing together B16-F10RR cells (universal fusers) and B16-F10 cells, allowing them to grow in close juxtaposition, and recovering putative hybrids in the appropriate selection media . The tumor cell-tumor cell composition of the resultant hybrids is inferred from the relative frequency of fusions, compared with the infrequency of tumor cell-host cell fusion when single populations of B16-F10RR cells were used, and by the chromosomal content of the hybrids . Definitive proof that hybridization occurs between both types of tumor cell rather than between a tumor cell and some other type of cell would require the use of a third biochemical marker on the unmarked tumor cells . I am now repeating these experiments using B16-F10 cells that exhibit resistance to the neomycinlike antibiotic G418 . Nonetheless, it is not surprising to find that such closely related tumor cells fuse with one another . The efficiency of in vitro hybridization mediated by polyethylene glycol is increased when the hybridizing cells are histologically or developmentally related, so that B16 melanoma cells fuse more readily with one another than they do with unrelated cells such as UV-2237 cells (I . Hart, unpublished observations) . Moreover, early hybridization protocols did not call for the use of fusogens, but merely the cocultivation of participating cells in the two-dimensional constraints of a tissue culture dish (e.g., Barski et al . 1961, Silagi 1967) . Presumably, the increased contact between cells within a growing tumor mass would increase the likelihood of such spontaneous fusion . In vivo hybridization could play a significant role in neoplastic progression and variation in metastatic efficiency by at least two separate, but not necessarily mutually exclusive, mechanisms . First, fusion of two contiguous tumor cells would increase the chromosome content of the resultant single cell; this increase in ploidy could facilitate and heighten the apparent inherent genetic instability of neoplastic cells (Nowell 1976) . Although segregation and chromosome loss may or may not be random or preferential in nature (Campbell and Worton 1981), the mere occurrence of such a phenomenon could also cause chromosomal disjunction and the possible extinction and reexpression of specific genes, which would lead to the independent variation and progression of different tumor cell characteristics in the manner cited by Foulds (1969).(ABSTRACT TRUNCATED AT 400 WORDS)

Int J Clin Pharmacol Res, 1983, 3(5), 357 - 61
Activity and tolerability of domifen bromide in patients affected by acute infectious dental diseases: a double-blind placebo-controlled trial; Scaglione F et al.; Thirty-one patients (21 M and 10 F), affected by acute infectious dental disease, were treated with domifen bromide (A) or placebo (Pl) . It was found that A had a beneficial effect on the results of clinical controls and reduced the need for the concomitant use of an antibiotic (p = 0.001 and p = .008 respectively) . Furthermore, after two days of treatment with A, there was a significant decrease in pain and inflammation (p less than 0.01) . A alone or in combination with an antibiotic elicits a good response, improves the prognosis and reduces the number of days of illness.

Comput Biol Med, 1983, 13(4), 287 - 97
Analysis of interactions between treatments applied concurrently onto biological systems; Ozanne G et al.; A program, written in BASIC, has been developed to analyse results of experiments studying individual and combined effect of two treatments (physical or chemical) on a biological system . Analysis is done in regard to: (1) level of significance selected for statistical test; (2) number of data available; (3) expected combined effect of treatments resulting from addition which is computed using an original formula; (4) experimental hypothesis tested . Using this program we have determined that there is a highly significant synergism between ampicillin (antibiotic) and amprolium (antiparasitic drug) to reduce the growth of some enteric bacterial strains which have a plasmidic resistance to ampicillin . Other applications are suggested.

Med Microbiol Immunol (Berl), 1983, 172(3), 137 - 47
Concurrent transfer and recombination between plasmids encoding for heat-stable enterotoxin and drug resistance in porcine enterotoxigenic Escherichia coli; Franklin A et al.; The frequency of and genetic mechanisms for simultaneous transfer of genes encoding for tetracycline and sulpha-streptomycin resistance, heat-labile (LT) and heat-stable (ST-mouse) enterotoxin production in porcine enterotoxigenic Escherichia coli to Escherichia coli K12 were investigated . Seven E . coli strains of 0-group 149 were studied by conjugation and transformation experiments . All strains transferred tetracycline-resistance plasmids at a high frequency . No interaction was observed between these plasmids and those encoding for LT production . However, most tetracycline-resistant recipient cells were ST-mouse+ following recombination events between plasmids encoding for colicin B and ST-mouse production and plasmids encoding for tetracycline resistance . Alternatively, when selecting for sulpha or streptomycin resistance a majority of the transconjugants were also ST-mouse+, as plasmids coding for sulpha and streptomycin were mobilized by the colicin B and ST-mouse encoding plasmid . Since the simultaneous transfer of genes encoding for drug resistance, colicin B and ST-mouse production are common events in vitro, they might also occur frequently in vivo during antibiotic selective pressure.

Acta Chir Scand, 1983, 149(5), 517 - 20
Septic complications after appendicectomy for perforated appendicitis . A controlled clinical trial metronidazole and topical ampicillin; Schultz A et al.; A prospective, controlled trial of antibiotic therapy was carried out in 90 patients with perforated appendicitis . One randomly selected group received systemic metronidazole, started peroperatively, plus locally instilled ampicillin . The other group, also randomly selected, received only local ampicillin . There was no statistically significant difference in the overall frequency of postoperative septic complications (wound infection or intra-abdominal abscess) between the two groups, but wound infections were significantly fewer in the patients given metronidazole . There was no intergroup difference in hospitalization time . Treatment with systemic metronidazole and local ampicillin is recommended in patients operated on for perforated appendicitis.

Mol Gen Genet, 1983, 190(3), 523 - 6
Genetic studies on the beta subunit of Escherichia coli RNA polymerase . III . Analysis of low-level rifampicin-resistant mutants; Boothroyd CM et al.; Spontaneously-occurring rifampicin-resistant mutants that survive on low (20 micrograms ml-1) but not high drug concentrations (200 micrograms ml-1) have been isolated . One such mutation appears to map close to residue 650 on the beta structural gene . RNA polymerase from low-level resistant strains shows an intermediate response to rifampicin in vitro: both the association and dissociation rates of the antibiotic are markedly reduced . Continued expression of this unusual phenotype upon introduction of a high-level resistance allele is described in terms of DNA blockade.

Poumon Coeur, 1983 Jan-Feb, 39(1), 53 - 7
{Double-blind study of an immunomodulator of bacterial origin (Biostim) in the prevention of infectious episodes in chronic bronchitis}; Viallat JR et al.; A double-blind trial was conducted to evaluate the capacity of an immunomodulator of bacterial origin (Biostim) to diminish the frequency of infectious episodes in chronic bronchitis . The study duration was 9 months, Biostim being administered orally initially, with follow-up examinations after 2 and 4 months . Of the 73 subjects selected, 38 received Biostim and 35 a placebo (no significant differences between the two groups) . By the 9th month, the duration in days of infectious episodes and of antibiotic therapy was 13 +/- 1.3 and 11.5 +/- 1.4 days respectively for the group receiving Biostim, and 33 +/- 5.8 and 41 +/- 9.5 respectively for the placebo group (p less than 0.05) . No signs of intolerance and particularly no immunotoxicity were observed: absence of elevation of IgE or anti-Biostim antibody titres . Pre-winter administration of Biostim to subjects at high risk would appear to significantly diminish the frequency of infectious episodes and thus the consumption of antibiotics.

Scand J Rheumatol, 1983, 12(2), 113 - 8
The role of the MA-sensitive leukocyte chemotaxis in rheumatoid arthritis . A randomized double-blind clinical trial of griseofulvin treatment; Nilsson F et al.; Polymorphonuclear leukocyte (PMN) chemotaxis is thought to play an essential role in the pathogenesis of rheumatoid arthritis . PMN chemotaxis is in part sensitive to microtubule antagonists (MAs), e.g . colchicine . The antimycotic antibiotic griseofulvin inhibits the MA-sensitive PMN chemotaxis in vitro in concentrations far below those obtained in serum during antimycotic therapy . The role of the MA-sensitive chemotaxis in rheumatoid arthritis could thus be elucidated by a clinical trial of griseofulvin treatment . Griseofulvin (n = 20) was tested in a randomized double-blind study versus placebo (m = 19) during one year in patients with rheumatoid arthritis of mild-moderate activity . No beneficial effect of griseofulvin treatment was noted on clinical symptoms or laboratory parameters of rheumatoid arthritis . Moreover, the placebo-treated patients showed more improvement than the griseofulvin-treated patients . It is therefore suggested that the MA-sensitive chemotaxis plays a reparative role in the inflammatory lesions of rheumatoid arthritis.

Mol Gen Genet, 1983, 189(1), 172 - 4
Relationship between cytoplasmic and mitochondrial apparatus of protein synthesis in yeast Saccharomyces cerevisiae; Surguchov AP et al.; A conditional respiratory deficiency in yeast Saccharomyces cerevisiae is expressed as a result of a nuclear mutation in sup1 and sup2 genes (II and IV chromosomes, respectively), coding for a component of cytoplasmic ribosomes (Ter-Avanesyan et al . 1982) . One such strain is studied here in detail . The strain is temperature-dependent and expresses a respiratory deficient phenotype at 20 degrees C but not at 30 degrees C . Moreover, the strain is simultaneously chloramphenicol-dependent and is able to grow on media containing glycerol or ethanol as a sole carbon source only in the presence of the drug . Chloramphenicol has a differential effect on protein synthesis in mitochondria of the parent strain and the mutant . Since chloramphenicol is a ribosome-targeting antibiotic we suggest that the differential effect of the drug on parent and mutant mitochondrial protein synthesis is due to the altered properties of mito-ribosomes of the mutant compared to those of the parent strain . Mitochondria of the mutant synthesize all the mitochondrially encoded polypeptides, however, in significantly lowered amounts . A suggestion is put forward for the existence of a common component (a ribosomal protein) for mito and cyto-ribosomes.

Ann N Y Acad Sci, 1983, 413, 47 - 56
Gene cloning in the actinomycetes; Taylor DP et al.; The production of antibiotics by soil-borne micro-organisms, the actinomycetes, has considerable economic importance . The manipulation of antibiotic producers has become a prime target for the application of recombinant DNA technology . Certain technical requirements have had to be met for gene cloning to be successful in the actinomycetes . These requirements, including the development of cloning vectors and transformation procedures, have been satisfied, in part, for some members of the Streptomyces genus . Some problems including sequence rearrangement and stability of plasmid maintenance are now being recognized . A number of genes have been cloned in Streptomyces and some preliminary results characterizing the gene for a Streptomyces-derived beta-galactosidase-like activity were described.

Biomed Biochim Acta, 1983, 42(7-8), 917 - 29
Adrenergic and antiadrenergic activity of cycloheximide in cultured rat heart cells; Wollenberger A et al.; Cycloheximide at concentrations between 10(-5) to 10(-3) M increased the rate of beating of rocker-cultured neonatal rat myocardial cells through activation of alpha 1-adrenoceptors . At concentrations between 3 X 10(-10) and 10(-6) M, at which {14C}-leucine incorporation into the cultured cells was not or not greatly affected, the antibiotic inhibited surmountably the positive chronotropic action of the rather nonselective beta-adrenergic agonist isoprenaline . It also antagonized the cyclic AMP response to isoprenaline . A powerful positive chronotropic action of the beta 2-selective agonist clenbuterol was not opposed by cycloheximide . Neither did cycloheximide (10(-8) and 10(-6) M) influence the acceleration of beating by phenylephrine, dibutyryl cyclic AMP, and elevation of the extracellular calcium concentration . Displacement of the nonselective beta-adrenoceptor ligand {125I}iodopindolol from its specific binding sites on the cultured heart cells by cycloheximide was diphasic, with 15 to 35 per cent of the displacement taking place below 10(-8) M cycloheximide (IC50 = = 2 X 10(-9) M) and the remaining 65 to 85 per cent above 10(-5) M . The action of low concentrations of cycloheximide on beta-adrenoceptors remains to be delineated.

Biomed Biochim Acta, 1983, 42(7-8), 867 - 83
Studies on histone H1 condensing properties in complexes with DNA and polydeoxyribonucleotides using netropsin as a probe; Burckhardt G et al.; The binding of histone H1 with DNA and synthetic DNA duplex polymers with respect to its property to induce higher ordered structures has been studied using the DNA binding antibiotic netropsin as a probe . It was shown that the formation of distinct steps of different condensed structures (double-fibers, cable- and stem-like forms) is influenced by the ionic strength . CD titration data of DNA-H1 complexes with netropsin at 20 mM NaCl indicated no change in the binding to strong affinity sites (dA X dT clusters) as compared to free DNA's, while weak netropsin binding regions are strongly affected by competition interaction with H1 . At low histone concentration the presence of netropsin favours the formation of double fibers . CD and electron microscopic findings indicated that at 20 mM NaCl the occurrence of condensed structures of DNA histone H1 complexes is not dependent on the base content . The major groove interaction of H1 most probably plays the major role in the formation of higher ordered structures . However, the minor groove binding might be involved as a secondary event . A hierarchy of relevant morphological structures observed for DNA-H1 complexes is presented.

Mol Gen Genet, 1983, 192(1-2), 131 - 9
Plasmid and chromosomal mutants in the iron(III)-aerobactin transport system of Escherichia coli . Use of streptonigrin for selection; Braun V et al.; Assimilation of iron via aerobactin by Escherichia coli requires functions encoded by certain ColV plasmids and by the chromosomal fhu region . Mutants obtained by insertion of the transposons Mu d1 (Ap lac) and Tn5 into ColV-K311 revealed that the aerobactin genes are transcribed from the locus that determines aerobactin synthesis to the gene encoding the outer membrane receptor protein for ferric aerobactin uptake . The antibiotic streptonigrin was used for selection of mutants impaired in iron assimilation . A simple assay was devised to identify mutants devoid of aerobactin synthesis . In addition, we performed complementation studies between fhu mutants and fhu genes cloned into pBR322 . The genes fhuC,D,B were required for uptake of ferric aerobactin . Mutations in the fhuA gene usually decreased expression of the subsequent fhuC,D,B genes to such an extent that growth on ferric aerobactin as sole iron source was abolished . The results suggest that the genes on the chromosome and on the ColV plasmid are organized in two operons.

J Cyclic Nucleotide Protein Phosphor Res, 1983, 9(2), 119 - 28
Evidence for intravesicular beta-adrenergic receptors in membrane fractions from desensitized cells: binding of the hydrophilic ligand CGP-12177 only in the presence of alamethicin; Hertel C et al.; Two fractions of beta-adrenergic receptors have been separated from desensitized C62B cells by centrifugation on a sucrose gradient . Using two beta-adrenergic receptor (beta AR) antagonists, 125I-iodopindolol and (3H)CGP-12177, the different binding characteristics of these fractions have been investigated . While iodopindolol binds to beta AR both in a light (30% sucrose) and a heavy (45-50% sucrose) peak, CGP-12177 binds only to those in the heavy peak . Incubation of these two gradient fractions with the antibiotic alamethicin selectively increases the binding of CGP-12177 only in the light peak . This result suggests that the desensitization-induced light peak beta AR exist on the inside of vesicles . The hydrophilic ligand CGP-12177 is capable of reaching these receptors only through alamethicin-formed pores.

Prog Neuropsychopharmacol Biol Psychiatry, 1983, 7(2-3), 287 - 96
Clinical implications of research on the mechanism of action of lithium; Belmaker RH et al.; Lithium is a unique drug in its clinical profile in psychiatry . Lithium has numerous biochemical effects, but none has yet been proven to be its mode of therapeutic action . Inhibition of noradrenaline-sensitive adenylate cyclase is reviewed as the only biochemical effect of lithium shown to occur in both animals and man at therapeutic lithium concentrations . A tetracycline antibiotic, demeclocycline, also blocks noradrenaline-sensitive adenylate cyclase . A clinical trial of demeclocycline in mania would provide a test of the adenylate cyclase theory of lithium action.

Arzneimittelforschung, 1983, 33(3), 427 - 9
{Tissue concentration of ceftizoxime in the lung}; Adam D et al.; 2 g ceftizoxime were administered as a i.v . bolus injection to 34 patients, in whom a lung operation was performed for either therapeutic or diagnostic reasons . At different time intervals after the injection, a lung biopsy was taken together with a serum sample to measure the antibiotic concentrations . The serum concentrations of ceftizoxime in these patients differed only slightly from results obtained with healthy volunteers . 60 min after injection, ceftizoxime-concentrations in the lung tissue varied between 7 and 15 micrograms/g (mean 11, n = 4) and declined slowly thereafter . After 4 h in two patients values of 2 and 4 micrograms/g ceftizoxime, respectively, were obtained . Even after 7 h concentrations of more than 1 microgram/g tissue were found.

Antimicrob Agents Chemother, 1983 Jan, 23(1), 119 - 24
Combined effect of acyclovir and amphotericin B on the replication of pseudorabies virus in BHK-21 cells; Malewicz B et al.; Acyclovir, known as an antiherpetic agent, showed an inhibitory effect on the propagation of pseudorabies virus in BHK-21 cells . The antiviral effect of acyclovir was observed by plaque reduction, as well as by the inhibition of the virus-stimulated uptake of thymidine by BHK-21 cells . Amphotericin B potentiated the antiviral activity of acyclovir . The optimal concentrations of polyene antibiotic expressing the potentiating effect were lower than required for the induction of K+ leakage from the cells . There was no evident amphotericin B-induced stimulation of thymidine incorporation into infected BHK-21 cells . The model presented may be useful to study the potentiation phenomenon of polyene macrolide antibiotics.

Rev Chir Orthop Reparatrice Appar Mot, 1983, 69(5), 381 - 91
{Atloido-axoid surgery by a transoral approach}; Louis R; The author has approached 18 atlanto-axial joints in 15 years by a transoral approach . Fourteen of the lesions were post traumatic, two congenital, one rheumatoid and one a tumour . It is concluded that the approach is a valuable one provided that there is adequate surgical technique, good antiseptic preparation, antibiotic therapy, provisional peroperative tracheostomy and special retractors . Use of adequate suture is also important . In some cases, magnification was needed . Medullary monitoring may also be helpful . The author estimates that the approach is more effective than extrabuccal techniques since it allows a direct exposure of the lesion . Large excisions are possible followed by reconstruction and grafting . It also allows screw fixation of the odontoid process . Two patients among earlier cases became infected but without serious long-term complications . Remaining cases have uncomplicated follow-up.

J Gen Microbiol, 1983 Jan, 129 (Pt 2), 245 - 50
Effect of papulacandin B on the cell wall and growth of Geotrichum lactis; Perez P et al.; Addition of the antifungal antibiotic papulacandin B to an exponential culture of Geotrichum lactis inhibited incorporation of glucose into the alkali-insoluble and alkali-soluble glucan fractions of the hyphal wall, although the rate of growth was practically unaltered . Synthesis of other cell wall components (i.e . galactomannan and chitin) was not affected . Papulacandin B also induced the proliferation of branches along the hyphae which continued to branch dichotomously resulting in a 'colonial' pattern of growth . Aculeacin A, another antifungal antibiotic that inhibited beta-glucan synthesis also caused morphological alterations similar to those described for papulacandin B . Inhibition of beta-glucan synthesis and the altered growth pattern persisted for several hours after removal of the antibiotic . Recovery of beta-glucan synthesis and restoration of the normal pattern of growth occurred simultaneously . Growth of G . lactis in L-sorbose medium also led to inhibition of beta-glucan synthesis and dichotomous branching.

Rev Neurol (Paris), 1983, 139(5), 375 - 9
{Whipple's disease with encephalopathy . A case report with review of the literature}; Leger JM et al.; A 58 year-old man developed a progressive encephalopathy four years after Whipple's disease onset with digestive, lymph node, and multiple joint lesions, treated over a period of two years . The diagnosis of neurological manifestations of Whipple's disease was based on clinical findings and the presence of PAS+ inclusion bodies in CSF cells . The outcome was fatal in spite of antibiotic therapy . Diagnostic features of this rare neurological affection are discussed . Preventive treatment and surveillance of patients with Whipple's disease are necessary even after well-conducted therapy.

Biomed Pharmacother, 1983, 37(7), 312 - 6
Inhibition of cardiac guanylate cyclase by doxorubicin and some of its analogs; Lehotay DC et al.; Doxorubicin, an anthracycline antibiotic and antitumor agent, has cardiotoxic side-effects that limit its therapeutic usefulness . We have demonstrated that the drug inhibits cardiac guanylate cyclase activity in vitro . The biochemical changes following anthracycline treatment are described, and the various hypotheses attempting to account for cardiotoxicity in terms of a molecular mechanism are reviewed . It is suggested that inhibition of cardiac guanylate cyclase activity may be a consequence of the increase in free radicals and oxidative damage following treatment with doxorubicin or related compounds.

Teratog Carcinog Mutagen, 1983, 3(6), 515 - 26
Cytogenetic effect of colistin on human lymphocytes in vitro: chromosome aberrations, sister chromatid exchanges, mitotic index, cell cycle kinetics, and acrocentric associations; Jaju M et al.; Colistin, a peptide antibiotic, was tested at three different concentrations--71, 142, and 214 units/ml . One hundred forty-two units per milliliter corresponds to the plasma level after receiving therapeutic dose . There was a dose-dependent increase in the frequency of chromosome aberrations irrespective of the duration of treatment (T0, T24, T48) . This antibiotic decreased the mitotic index and delayed the cell turn over rate indicating inhibition of DNA synthesis by it . Inhibition of DNA synthesis probably results in increase in the frequency of chromosome aberrations . Frequency of satellite associations of acrocentric chromosomes was increased with increasing concentration of the drug, but the differences at three concentrations were not significant compared to controls . There was no increase in the frequency of SCEs at any concentration or duration of treatment compared to controls . It appears that colistin induces the type of lesions that lead to chromosome aberrations and not to SCEs.

Am J Trop Med Hyg, 1983 Jan, 32(1), 31 - 3
Antitrypanosomal activity of sinefungin; Dube DK et al.; Sinefungin, a naturally occurring antifungal antibiotic nucleoside containing an ornithine residue, linked by a C-C bond to C-5' of adenosine, cures mice infected with Trypanosoma brucei brucei, T . congolense, or T . vivax; the effect of the drug is more pronounced towards T . congolense . Anti-trypanosomal activity of sinefungin could be the result of the inhibition of transmethylation reactions or of polyamine biosynthesis--or both--in parasites.

Tumori, 1982 Dec 31, 68(6), 499 - 504
Reduction of lethal toxicity of doxorubicin by amrinone; Bossa R et al.; Administration of amrinone, a new inotropic agent, markedly reduced acute lethal toxicity in normal female Swiss and male BALB/c mice given lethal doses of doxorubicin . Because amrinone abolished the negative inotropic effect of doxorubicin in isolated guinea pig atria, it was suggested that partial protection from acute toxicity of the antitumor antibiotic is directly related to protection of cardiac function.

Biochim Biophys Acta, 1982 Dec 22, 693(2), 466 - 78
Calorimetric investigation of polymyxin binding to phosphatidic acid bilayers; Sixl F et al.; The cooperative binding process between the antibiotic peptide polymyxin-B and negatively-charged phosphatidic acid bilayers was investigated by differential thermal analysis and completed by fluorescence polarization measurements . The sigmoidal binding curves were analyzed in terms of the interaction energy within a domain formed by polymyxin and phosphatidic acid molecules . The formation of such a heterogeneous domain structure was favoured by high concentration of external monovalent ions . The cooperativity of the binding increased while a charge-induced decrease in the phase transition temperature of the pure lipid phase was observed with increasing ion concentration at a given pH . The reduced lateral coupling within the lipid bilayer in the presence of salt ions, as demonstrated by an increase in the lipid phase transition enthalpy, was considered to facilitate the cooperative domain formation . Moreover, an increase in the cooperativity of the polymyxin binding could be observed if phosphatidic acids of smaller chain length and thus of a lowered phase transition temperature were used . By the use of chemically-modified polymyxin we were able to demonstrate the effect of electrostatic and hydrophobic interaction . Acetylated polymyxin with a reduced positive charge was used to demonstrate the pure hydrophobic effect of polymyxin binding leading to a decrease in the phosphatidic acid phase transition temperature by about 20 degrees C . The cooperativity of the binding was strongly reduced . Cleavage of the hydrophobic polymyxin tail yielded a colistinnonapeptide which caused an electrostatically-induced increase in the phosphatidic acid phase transition temperature . With unmodified polymyxin we observed the combined effects of electrostatic as well as hydrophobic interaction making this model system interesting for the understanding of lipid-protein interactions . Evidence is presented that the formation of the polymyxin-phosphatidic acid complex is a lateral phase separation phenomenon.

Z Hautkr, 1982 Dec 15, 57(24), 1787 - 1801
{Huge gangrenous cellulitis . Clinical symptoms-differential diagnosis--therapy}; Schmeller W; Extensive necrotizing cellulitis occurs in adults, when body resistance is reduced by serious general disorders . Differential diagnosis should exclude the following diseases: gangrenous erysipelas, necrotizing fasciitis, gangrenous ecthyma, pyoderma gangrenosum, purpura fulminans and Coumarin necrosis . In addition to antibiotic therapy, the removal of vast necrotic areas as well as plastic covering is necessary . A case of typical predisposing disorders, clinical symptoms and development of the disease is reported.

Drug Inf J, 1983, 17(3), 171 - 5
FDA approval of comparative claims for prescription drugs--the Moxam case; Marcus D; FDA allowance of comparative claims as part of the approved labeling for new prescription drugs creates special problems . Claims contained in prescription drug labeling are viewed by physicians as embodying not just the normal puffery of the manufacturer, but the considered views of government agency charged with protecting public health . Thus, labeling claims for prescription drugs have an impact and significance that promotional claims for other products do not . In the Moxam case--a dispute between Upjohn and Lilly over the FDA's approval of a comparative claim for a new Lilly antibiotic--the agency recognized this fundamental reality . Faced with the prospect of having to provide a procedure to permit competitors to challenge approval of comparative claims, the FDA has moved toward a policy of not permitting such claims in labeling, while allowing them in advertising.

Biochemistry, 1982 Dec 7, 21(25), 6496 - 503
Biosynthesis and characterization of {15N}actinomycin D and conformational analysis by nitrogen-15 nuclear magnetic resonance; Shafer RH et al.; We describe the production and characterization of actinomycin D labeled with 15N at all twelve nitrogen positions . Cultures of Streptomyces parvulus were incubated in the presence of racemic {15N}glutamic acid and, following an initial delay, labeled antibiotic was produced . Evidence is presented that the D enantiomorph of glutamic acid was ultimately used for actinomycin biosynthesis . The 15N NMR spectrum at 10.14 and 20.47 MHz of the labeled drug in CDCl3 is presented . All nitrogens except the phenoxazone chromophore nitrogen are inverted when spectra are obtained under broad-band proton irradiation conditions . All 15N resonances have been assigned, and the proton-nitrogen one-bond coupling constants were determined in CDCl3 to be 92.5 +/- 0.3 Hz for the valine and threonine amide protons by both 1H and 15N NMR . 15N NMR spectra were also obtained in dimethyl sulfoxide, methanol, and water in order to probe solvent interactions with the peptide nitrogens and carbonyl groups . Large downfield shifts (greater than 5 ppm) were seen for the Pro, sarcosine, and methylvaline resonances when the solvent was changed from dimethyl sulfoxide to water . Smaller downfield shifts were observed for the Val and Thr peaks . These results are discussed in terms of a model for the solution conformation of the actinomycin pentapeptide rings based on different hydrogen-bonding interactions in the monomer in organic solvents and the dimer which is formed in water.

Vet Hum Toxicol, 1982 Dec, 24(6), 406 - 9
Preliminary studies on lasalocid toxicosis in cattle; Galitzer SJ et al.; Polyether antibiotics are gaining widespread use in the feedlot cattle industry . One such investigational antibiotic, Lasalocid, was studied at oral doses of 25, 50, 75, 100 and 125 mg/kg to determine effects of toxicosis in six cattle . Deaths occurred at 100 and 125 mg/kg body weight . The general syndrome developed as muscle tremors, increased heart rate and respiration rate followed by or concurrent with anorexia (within 24 hr) and watery, forced diarrhea (48 through 72 hr) . There were signs of cardiac effects one week to ten days after administration of the drug.

J Antibiot (Tokyo), 1982 Dec, 35(12), 1658 - 64
Albocycline: structure determination by x-ray crystallography; Thomas RC et al.; The structure and absolute configuration of the macrolide antibiotic albocycline (1a) has been determined by X-ray crystallographic analysis on the derived p-bromobenzoate (1b) . The absolute configuration of albocycline is 4R, 7S, 12S, 13R.

Antibiotiki, 1982 Dec, 27(12), 51 - 3
{Pharmacokinetics of ampicillin in children with respiratory infections}; Danilova VI et al.; The pharmacokinetics of ampicillin was studied in 30 children with diseases of the upper respiratory tracts . The data obtained with a single administration of anhydrous ampicillin in a dose of 25 mg/kg were estimated on one-compartment model . It was shown that the maximum antibiotic levels in the serum were attained in 1.52 hours and averaged to 4.56 micrograms/ml . The antibiotic half-life was 1.24 hours . The period of half-absorption of the antibiotic was 0.66 hours . Comparison of the experimental results with the literature data showed that the pharmacokinetic properties of anhydrous ampicillin and ampicillin trihydrate were close.

Antibiotiki, 1982 Dec, 27(12), 46 - 50
{Transplacental passage of gentamicin and its effect on the fetus}; Nichoga LA et al.; The time course of gentamicin transplacental penetration was studied in women during labor . It was found that the transplacental penetration of the antibiotic was high and its levels in the fetus blood were only slightly lower than those in the mother blood . The concentration of the antibiotic in the placenta and amniotic fluid was also rather high . The experiments with rats showed that the levels of gentamicin penetration into the fetus depended on the pregnancy period: at earlier periods (13 days) the level of gentamicin transplacental penetration was 5.8 times higher than that at later periods (21 days) . In high doses gentamicin produced an embryotoxic effect, therefore in treatment of pregnant women with gentamicin its therapeutic doses should not be exceeded.

Antibiotiki, 1982 Dec, 27(12), 34 - 8
{Pharmacokinetics of cefamandole in rabbits}; Klimova VS et al.; The pharmacokinetics of cephamandol administered intramuscularly in single doses of 5 or 20 mg/kg and intravenously in a single dose of 5 mg/kg was studied on rabbits . When the antibiotic was administered intramuscularly, a one-compartment model was used for determination of the parameters of the antibiotic pharmacokinetics in the blood serum, while on intravenous administration of the antibiotic a two-compartment model was used . It was found that the rate of cephamandol elimination after intramuscular administration did not depend on the drug dose . The antibiotic half-life was 34-37 minutes . The apparent volume of the antibiotic distribution after intramuscular administration was 0.31-0.71 ml/g . After intravenous injection of cephamandol the apparent volume of its distribution in the central compartment was 0.27 ml/g . The stationary and kinetic volumes of the antibiotic distribution were 0.36 and 0.46 ml/g, respectively . The average values of the antibiotic elimination constant, the constant of the antibiotic passage from the central compartment to the peripheral one and vice versa were 0.0446, 0.0193 and 0.0546 min-1, respectively . After intravenous injection the rate of cephamandol elimination from the rabbit blood was higher: the antibiotic half-life after intravenous injection was 26.1 min.

J Clin Hosp Pharm, 1982 Dec, 7(4), 245 - 50
The stability of amoxycillin sodium in intravenous infusion fluids; Cook B et al.; The stability of amoxycillin sodium has been determined at 25 degrees C in water and in ten intravenous infusion fluids at concentrations of 1, 2 and 5% w/v . Little difference in stability was found between 1% and 2% amoxycillin solutions in the various vehicles, but the antibiotic was significantly less stable at 5% . Stabilities in sodium and potassium chloride solutions were similar to those in water and were markedly superior to those in dextrose or dextran fluids . Solutions in lactate or bicarbonate had intermediate stability . The antibiotic was, for practical purposes, unstable in 30% sorbitol solution . Guidelines are provided for intravenous infusion of amoxycillin in the solutions studied.

Antimicrob Agents Chemother, 1982 Dec, 22(6), 1087 - 9
Cefamandole bile levels in patients with hepatobiliary disease; Uwaydah M et al.; Intraoperative biliary cefamandole concentrations were determined in 16 patients with hepatobiliary pathology . These included seven patients with cholelithiasis, five with acute cholecystitis, two with recurrent ascending cholangitis, and two with liver abscesses . Bile collected 0.5 to 2.5 h after the last antibiotic dose of 1 g administered by intravenous drip showed therapeutically effective concentrations of cefamandole in 84% (11 of 13) of gall bladder samples with a median of 220 micrograms/ml (range, 1.6 to 1,400), and in 100% (13 of 13) of common bile duct samples with a median of 1,100 micrograms/ml (range, 9.0 to greater than 2,000) . Only with complete aseptic cystic duct obstruction was cefamandole undetectable in gall bladder bile.

Am J Surg, 1982 Dec, 144(6), 660 - 7
Percutaneous catheter drainage in intraabdominal fluid collections including infected biliary ducts and gallbladders; Miller MH et al.; Sixty-five abscesses, including 6 infected biliary systems and 15 sterile fluid collections, were treated by percutaneous catheter drainage in 77 febrile patients who were evaluated by computerized tomography or ultrasonography of intraabdominal infection . Percutaneous catheter drainage and systemic antibiotic administration without surgery provided satisfactory control of infection in 52 of 65 abscesses (80 percent) . Catheter drainage followed by surgical exploration for abscess control was performed in an additional 5 of 65 abscesses (7 percent) . Nine death (14 percent) occurred in the abscess group of 64 patients . In 15 patients, aspirations, Gram stain, and culture of the abnormal fluid collection revealed sterile fluid . Drainage with a single catheter allowed complete resolution in 14 of 15 sterile collections . Surgery was performed electively in one patient with a fistula from a pancreatic pseudocyst in the small bowel . No deaths occurred in the noninfected group of 15 patients, 2 of whom underwent drainage of coexisting abscesses.

Am J Obstet Gynecol, 1982 Dec 1, 144(7), 841 - 8
Complications of abdominal and vaginal hysterectomy among women of reproductive age in the United States . The Collaborative Review of Sterilization; Dicker RC et al.; PIP: Although hysterectomy was the most frequently performed major surgical procedure among women of reproductive age during the past decade, few recent studies have been conducted to determine the risk of complications . We examined data from the Collaborative Review of Sterilization, a prospective, multicenter, observational study coordinated by the Centers for Disease Control, to assess the comparative risks of complications among women undergoing hysterectomy by the abdominal and vaginal approaches . Between September 1978-August 1981, 1851 women from 9 institutions were included in the study . Women who underwent vaginal hysterectomy experienced significantly fewer complications than women who had undergone abdominal hysterectomy . The difference was probably attributable to the prevalence and efficacy of prophylactic antibiotic use among the former group . Vaginal hysterectomy was associated with more unintended major surgical procedures but less febrile morbidity, bleeding requiring transfusion, hospitalization, and convalescence than abdominal hysterectomy . Vaginal hysterectomy with prophylactic antibiotics should be strongly considered for those reproductive age women for whom either surgical approach is clinically appropriate . author's modified

Am J Dis Child, 1982 Dec, 136(12), 1054 - 6
Osteomyelitis as a cause of brachial plexus neuropathy; Clay SA; Two infants, younger than 2 months of age, had brachial plexus involvement and true paralysis secondary to osteomyelitis of the proximal humerus . To date, no previous cases of this association have been reported . Electromyography (EMG) demonstrated significant denervation in muscles innervated by the upper trunk, with scattered involvement of other muscles . Nerve conduction velocities were normal in both patients . Both patients had significant residual weakness after appropriate antibiotic therapy . One patient, 12 months after therapy for osteomyelitis, continued to demonstrate both clinical and EMG evidence of a lower motor neuron neuropathy . The pathophysiologic cause was thought to be ischemic nerve damage secondary to occlusion of vasa nervorum.

Jpn J Antibiot, 1982 Dec, 35(12), 2779 - 84
{Clinical studies on cefmetazole in respiratory infections}; Harada S et al.; Cefmetazole (CMZ) was used for the treatment of respiratory infections in 10 cases; six cases of bronchopneumonia, 2 cases of acute exacerbation of chronic pulmonary emphysema or bronchitis disease, 1 case of acute exacerbation of chronic respiratory failure and 1 case of lung abscess . CMZ was administered by intravenous drip infusion at a daily dose of 2 to 4 g for 5 to 24 days . Intramuscular injection of gentamicin was combined in 2 cases . Clinical results were as follows; excellent in 6 cases, good in 2 cases, fair in 1 case and poor in 1 case . As to the side effects of the drug, allergic reaction with fever and eosinophilia was observed in 1 case . This side effect disappeared immediately after cessation of CMZ . In view of the above, CMZ may be considered to be a clinically useful antibiotic against respiratory infections.

J Gen Microbiol, 1982 Dec, 128 (pt 12), 3051 - 60
Effect of tunicamycin on exo-1,3-beta-D-glucanase synthesis and secretion by cells and protoplasts of Saccharomyces cerevisiae; Sanchez A et al.; Addition of tunicamycin to the culture medium of growing Saccharomyces cerevisiae protoplasts or cells resulted in the formation of a modified exo-1,3-beta-D-glucanase which was detectable in both extracellular and intracellular fractions . This modified enzyme had a lower molecular weight than the native form and did not bind to concanavalin A . The activation energy and Km values of both enzyme forms were identical . Antibodies raised against the native protein readily precipitated the exo-1,3-beta-D-glucanase produced after tunicamycin treatment . The latter enzyme was comparable, in terms of molecular size and lack of affinity for concanavalin A, to the beta-D-glucanase obtained by treatment of the native form with endoglycosidase H; both lacked the carbohydrate moiety present in the native enzyme . The exo-1,3-beta-D-glucanase obtained in the presence of the antibiotic was more sensitive to variations in temperature and pH than both endoglycosidase H-treated and non-treated enzymes . Our results suggest that the carbohydrate moiety, if not necessary for exo-1,3-beta-D-glucanase secretion, may play a role in the conformation of the protein and in stabilizing the enzymic activity.

Gene, 1982 Dec, 20(3), 451 - 7
Development of cloning vehicles from the Streptomyces plasmid pFJ103; Richardson MA et al.; A 20-kb plasmid, pFJ103, was isolated from a strain of Streptomyces granuloruber . A restriction endonuclease map of the plasmid was constructed . A Streptomyces gene that specifies resistance to the antibiotic thiostrepton was subcloned into Escherichia coli plasmid pBR322, inserted into pFJ103 and transformed into Streptomyces ambofaciens protoplasts . Two classes of transformants were obtained . One carries the pFJ104 plasmid consisting of the entire pFJ103 with the 1.8-kb thiostrepton resistance gene insert . The other carries the pFJ105 plasmid consisting of the 2.9-kb replicon segment of pFJ103 with the same thiostrepton resistance insert . A gene for neomycin resistance together with the entire E . coli pBR322 plasmid were cloned into pFJ105 . The resulting E . coli-Streptomyces bifunctional vector, pFJ123, transformed both E . coli and Streptomyces . The small size of pFJ105, its ease of isolation, and efficient transformation of Streptomyces protoplasts establishes it, and its derivatives, as useful plasmid cloning vehicles for fundamental and applied studies.

Antiviral Res, 1982 Dec, 2(6), 331 - 7
Antiviral efficacy of pyrazofurin against selected RNA viruses; Canonico PG et al.; The antibiotic pyrazofurin, 3-(beta-D-ribofuranosyl)-4-hydroxypyrazole-5-carboxamide, markedly inhibited the in vitro replication of a number of RNA viruses including Rift Valley fever (RVF), Venezuelan equine encephalomyelitis (VEE), Sandfly, Pichinde, Lassa and LCM virus . Plaque formation was reduced by 80% or more with 2-10 micrograms/ml of pyrazofurin while 2 micrograms/ml reduced by 1000-fold the yield of Lassa and LCM virus in a yield reduction assay . In vivo, pyrazofurin failed to protect mice and guinea pigs against a lethal challenge with VEE and Pichinde virus, respectively . On the other hand, pyrazofurin caused a slight increase in the mean time to death of mice infected with RVF virus.

Gastroenterol Jpn, 1982 Dec, 17(6), 550 - 7
Enteric coated polymyxin B in the treatment of hyperammonemia and endotoxemia in liver cirrhosis; Adachi Y et al.; Effects of enteric coated polymyxin B capsules on hyperammonemia and endotoxemia in liver cirrhosis were investigated . Six million units of polymyxin B were orally administered daily to 21 patients with liver cirrhosis and 3 patients with hepatoma cum liver cirrhosis, whose plasma ammonia was higher than normal limit and/or whose plasma endotoxin was positive, for 5-32 days, and serum polymyxin B concentration (in 5 cases), changes of plasma ammonia level (in 19 cases) and plasma endotoxin (in all cases) were observed . Serum polymyxin B concentration was below the detectable limit (0.5 unit/ml) in all cases observed . In the patients with liver cirrhosis, plasma endotoxin and ammonia levels decreased rapidly after polymyxin B treatment, and the decreases in endotoxin levels were kept throughout the treatment . Twelve patients with liver cirrhosis (10 among them were treated with lactulose) were served as controls . All patients who were treated with lactulose alone showed rapid decrease in plasma ammonia, but the decrease in endotoxin in these patients was slower than that in those treated with polymyxin B . From these results, oral administration of polymyxin B is concluded to be useful in the treatment of hyperammonemia and endotoxemia in liver cirrhosis, as a poorly absorbed antibiotic and as an antiendotoxin agent.

Can Med Assoc J, 1982 Dec 1, 127(11), 1097 - 102
{Infections of the central nervous system caused by enterovirus: 223 cases seen at a pediatric hospital between 1973 and 1981}; Thivierge B et al.; Between 1973 and 1981, 223 patients were seen at hopital Sainte-Justine in Montreal for enteroviral infection of the nervous system . In 161 the cause was documented by isolation of an enterovirus from the cerebrospinal fluid (CSF) . The viruses most frequently isolated were echovirus 11 (36 isolates), echovirus 30 (24), coxsackievirus B2 (23), coxsackievirus B3 (19), echovirus 6 (18), coxsackievirus B5 (16), coxsackievirus A9 (15), echovirus 9 (13), echovirus 7 (12) and coxsackievirus B1 (11) . Aseptic meningitis was diagnosed in 200 cases and encephalitis in 12 . The remaining 11 patients presented with the features of septicemia or with convulsions . In 33 patients an enterovirus was isolated from the CSF in the absence of pleocytosis . Polymorphonuclear cell predominance was noted in the initial CSF sample in 95 cases; it was persistent in 11 . There were five mixed infections; in three cases two viruses were isolated from the same CSF sample . Two patients died: one, a child with hypogammaglobulinemia, had fatal polioencephalitis; the other, a 6-month-old infant brought to the emergency room in unexplained cardiopulmonary arrest, had echovirus 6 meningitis . Of the 172 patients admitted to hospital 96 received parenteral antibiotic therapy . The impact of enteroviral infections of the central nervous system on hospital resources could be substantially reduced if a rapid, sensitive and specific laboratory method of diagnosing these infections were available.

Geburtshilfe Frauenheilkd, 1982 Dec, 42(12), 895 - 8
{Experience with lamoxactam in gynecology: application as a monotherapeutic agent in severe genital infections and determination of its concentration in uterine and tubal tissues}; Petersen EE et al.; In 30 patients with genital infections of different etiology and high fever lamoxactam was used as a single agent antibiotic . In 90% of the cases the treatment was successful . The antibiotic did not need to be changed in any of the cases . The determination of the lamoxactam concentration in the uterus and the fallopian tubes after a single dose of 2 grams pre-operatively at various times showed high tissue levels for a prolonged period of time . The concentrations were still higher 6 hours after the single dose than the in vitro MHK values for most bacteria important in gynaecological infections.

Biull Eksp Biol Med, 1982 Dec, 94(12), 26 - 7
{Dependence of cordycepin inhibition of heterogeneous nuclear RNA biosynthesis in rat brain on the size of the poly(A) segments}; Kuznetsov DA et al.; A study was made of the effect of cordicepin on the biosynthesis of rat brain heterogeneous nuclear RNA (hnRNA) fractions, such as poly(A-)hnRNA, oligo(A+)hnRNA and poly(A+)hnRNA differing in the size of poly(A)-segments . Cordicepin was shown to inhibit the biosynthesis of poly(A+)hnRNA alone . However, small doses of the antibiotic do not virtually inhibit the biosynthesis of hnRNA with shorter segments of poly(A) . At the same time they inhibit the biosynthesis of hnRNA containing long chains of poly(A) in the 3'-end . A possible molecular mechanism of the phenomenon reviewed is under discussion.

N Z Med J, 1982 Nov 24, 95(720), 826 - 7
Septic abortion in an IUCD user; Conaghan CJ et al.; PIP: A 27-year old woman admitted to the hospital after 5 days of vaginal bleeding at 12 weeks gestation had had a copper-T IUD inserted 10 months previously . The IUD string was no longer visible at pregnancy testing . Prior to admission she had experienced lower abdominal pain, increasingly heavy vaginal bleeding, fever, malaise, chills, and vomiting . Intravenous ampicillin and metronidazole were commenced and the uterus was evacuated under a general anesthetic . The copper-T was removed from the uterine cavity . A uterine swab at operation and preoperative blood cultures grew E . coli . A moderate degree of disseminated intravascular coagulation (DIC) was indicated by a coagulation profile . The case demonstrates that the copper-T may be associated with intrauterine sepsis and DIC . In the 1st trimester the risk of abortion following removal of a device is near 30%, while the rate of abortion for women in whom the string is no longer visible is near 48% . Patients presenting with pregnancy in the presence of an IUD and symptoms of sepsis should have the uterus evacuated under suitable antibiotic cover .

Biochemistry, 1982 Nov 23, 21(24), 6309 - 12
Characterization of chlortetracycline (aureomycin) as a calcium ionophore; White JR et al.; The antibiotic chlortetracycline (aureomycin) is shown to be a potent and specific calcium ionophore . The molecule extracts calcium from an aqueous environment into a bulk organic phase in a pH-dependent manner and with a stoichiometry indicative of a 1:1 complex . The antibiotic has little affinity for other alkaline earth ions or alkali metal ions in this system . The ionophore transports calcium from one aqueous phase to another across an organic solvent barrier and induces a flux of calcium into multilamellar vesicles . The potential use of the compound in examining the role of calcium in the modulation of cellular function is discussed.

Biochim Biophys Acta, 1982 Nov 22, 692(3), 377 - 83
The effect of amine structure on complexation with lasalocid in model membrane systems . II . Ionophore selectivity for amines in lipid bilayers and at oil/water interfaces; Kinsel JF et al.; The ionophore antibiotic X-537A (lasalocid) transports biogenic amines across biological and artificial membranes . The major portion of amine flux (greater than 99%) occurs as a 1:1 neutral complex . The rank order of ionophore selectivity was determined for lipid bilayer membrane transport of amines based on a comparison of permeability coefficients: p-tyramine approximately beta-phenylethylamine approximately amphetamine greater than methamphetamine greater than dopamine greater than phenylephrine approximately metanephrine greater than norepinephrine greater than epinephrine . This rank order is in agreement with results obtained from partitioning measurements which were carried out in parallel to the bilayer membrane experiments . A correlation between amine structure and binding characteristics has been developed.

Nouv Presse Med, 1982 Nov 18, 11(46), 3379 - 84
{Discovery of dibekacin and its chemical aspects}; Umezawa H; The advent of strains resistant to antibiotics in some patients has led to reorientation of research in this field . Demonstration of the mechanism involved in resistance to aminosides has resulted in the development of derivatives active against these resistant strains . Dibekacin, a new aminoside, is the first semisynthetic antibiotic of this class to be developed, and represents the first application of carbohydrate chemistry to the industry . It possesses potent activity and very weak ototoxicity.

Nouv Presse Med, 1982 Nov 18, 11(46), 3456 - 8
{Evaluation of cochlear and vestibular functions of patients treated by dibekacin in an E.N.T . unit}; Uziel A et al.; Cochlear and vestibular ototoxicity of dibekacin was evaluated in 27 patients treated with aminoglycoside after surgery on head and neck cancer . The treatment was administered intramuscularly or intravenously during 13 days at the schedule of 3 mg/kg per day . Cochlear and vestibular functions were tested by audiometry and electronystagmography before the administration of the antibiotic and on the 14th, 30th day, and for certain patients on the 4th month after the start of the treatment . No cochlear ototoxicity was found after the dibekacin treatment . On the other hand, the dibekacin treatment produced minor abnormalities of ENG (irritative pattern).

Biochemistry, 1982 Nov 9, 21(23), 5862 - 70
Interaction of copper(II) ions with the daunomycin-calf thymus deoxyribonucleic acid complex; Spinelli M et al.; The interaction of Cu(II) with the native and heat-denatured DNA complexes of daunomycin (1) and N-(trifluoroacetyl)daunomycin (3) has been examined by using absorption and circular dichroism spectroscopies . At low rt, where rt is the input molar ratio of drug to DNA phosphate, Cu(II) interacts with the native and heat-denatured calf thymus DNA complex of daunomycin to form a ternary complex involving the aglycon portion of the antibiotic, Cu(II), and DNA . A Job plot of the titration involving Cu(II) and heat-denatured DNA shows that the Cu(II)-drug stoichiometry in the ternary complex is less than or equal to 1 . Although the N-(trifluoroacetyl)daunomycin-native DNA complex does not form a ternary complex, the denatured DNA complex with the antibiotic does . Copper(II) titrations of the daunomycin-native DNA complex, at high rt, where both strongly and weakly bound antibiotic molecules are very likely present in solution result in the formation of both the ternary species as well as a binary complex involving only the metal ion and the antibiotic . The spectroscopic results indicate that in the ternary complex, the Cu(II) ion is bound to the unintercalated aglycon portion of the antibiotic and very likely also to the heterocyclic bases of DNA.

Biochemistry, 1982 Nov 9, 21(23), 5857 - 62
Inhibition of mammalian deoxyribonucleic acid synthesis by neocarzinostatin: selective effect on replicon initiation in CHO cells and resistant synthesis in ataxia telangiectasia fibroblasts; Povirk LF et al.; Treatment of CHO cells with low doses of the protein antibiotic neocarzinostatin severely inhibited DNA replicon initiation but had no effect on chain elongation . The selectivity of the effect on initiation, which was greater than that seen with other chemical agents and comparable to that seen with X-rays, explains the biphasic dose response seen for DNA synthesis inhibition by this drug . Parallel experiments employing the nucleoid sedimentation technique indicated that half-maximal relaxation of domains of DNA supercoiling and half-maximal inhibition of replicon initiation required the same dose of neocarzinostatin, approximately 0.03 micrograms/mL . These results, similar results obtained with the protein antibiotic auromomycin, and previous results obtained with X-rays suggest a quantitative correlation between inhibition of replicon initiation and induction of sufficient strand breakage to relax domains of supercoiling in DNA of mammalian cells . Results in human ataxia telangiectasia fibroblasts indicated that neocarzinostatin, like X-rays, is much less effective in inhibiting DNA synthesis in these cells than in normal human fibroblasts . This finding is consistent with the hypothesis that the genetic defect in ataxia telangiectasia involves a failure to recognize the presence of strand breaks in cellular DNA.

Biochim Biophys Acta, 1982 Nov 8, 692(2), 238 - 43
Nystatin effects on cellular calcium in Saccharomyces cerevisiae; Eilam Y et al.; The primary effects of nystatin, a polyene antibiotic, on the yeast Saccharomyces cerevisiae were investigated . Though K+ leakage was observed shortly after the addition of nystatin, Ca2+ leakage was delayed 2-3 h after its application and it occurred only at an acidic pH and in the absence of K+, Na+ or Mg2+ from the medium . However, within 4 min after application nystatin induced a passive influx of Ca2+ into the cells even at a concentration of 1 microM in the medium . These results led to the conclusion that the primary membranal lesion induced by nystatin is not restricted to monovalent cations but is also manifested by increased permeability to Ca2+ . The delayed leakage of Ca2+ is explained by the assumption that the bulk of cellular calcium is sequestered so that the concentration of free Ca2+ in the cytoplasm is very low . The sequestered calcium may be liberated 2-3 h after the addition of nystatin as a consequence of secondary damage to the cells such as intracellular acidification and loss of cations.

Antibiotiki, 1982 Nov, 27(11), 827 - 30
{Effect of amphotericin B on the interferonogenic activity of poly(G) . poly(C) and poly(G,I) . poly(C) in mice and their resistance to infection by the tick-borne encephalitis virus}; Vil'ner LM; It was shown that amphotericin B, a polyenic macrolide markedly potentiated in mice the interferonogenic activity of the two-strand synthetic polyribonucleotide complexes, Poly (G) . Poly (C) and Poly (G, I) . Poly (C) . At the same time amphotericin B used in high or low doses lowered or somewhat increased respectively the protective effect of Poly (G) . Poly (C) and Poly (G, I) . Poly (C) which was not adequate to the antibiotic effect on their interferonogenic activity . It was found that amphotericin B stimulated in the mice the infection caused by the forest spring encephalitis virus, accelerated the period of its manifestation and increased the death rate . This effect correlated with the concentration of amphotericin B and the dose of the virus . The relationship between the differential effect of amphotericin B on the interferonogenic and antiviral activity of polyribonucleotide interferonogenes and the stimulation of the viral infection by them is discussed.

Antibiotiki, 1982 Nov, 27(11), 820 - 3
{Determination of carminomycin and its basic metabolite 13-dihydrocarminomycin by a highly efficient liquid chromatographic method with a fluorescent detector}; Poteshnykh AV et al.; Carminomycin, an antitumor antibiotic, and 13-dihydrocarminomycin, its main metabolite, were determined in the blood plasma of patients with highly efficient liquid chromatography and a fluorescent detector (lambda ex=492 nm, lambda em=538 nm) . The liquid chromatograph manufactured by Spectro-Physics, model SP-8000, with Particyl Column 10/25 was used for the determination . The composition of the mobile phase of acetonitrile--0.1 M H3PO4 was 93:7 by the volume . The mobility speed was 2 ml/min . The retention time of carminomycin, rubomycin (used as the national standard) and dihydrocarminomycin was 6.8, 8 and 10.2 minutes, respectively . All three substances showed symmetrical peaks with high resolution . The early phase kinetics of carminomycin after its intravenous injection to the patients in a dose of 24 mg (18 mg/m2) is satisfactorily described by the diexponential equation . The pharmacokinetic parameters of carminomycin corresponding to the open two-compartmental system are presented . Highly efficient liquid chromatography may be used for the pharmacokinetic description of biotransformation of carminomycin and some other antibiotics of the anthracycline group.

Antibiotiki, 1982 Nov, 27(11), 815 - 20
{Effect of crystallinity on the rate of solution of oxytetracycline hydrochloride}; Grakovskaia LK et al.; The crystal structure of 2 forms of oxytetracycline hydrochloride prepared with the method of crystallization from various solvents was studied . It was shown that these forms were 2 polymorphic modifications of the antibiotic with different crystal structures . The modification prepared with the method of crystallization from methanol was characterized by better dissolution in water . Its dissolution rate constant was 3 times as higher which makes this crystalline modification of oxytetracycline hydrochloride preferable for preparation of the antibiotic pharmaceutical forms with high bioavailability levels.

J Antibiot (Tokyo), 1982 Nov, 35(11), 1565 - 70
Biosynthesis of nanaomycin . III . Nanaomycin A formation from nanaomycin D by nanaomycin D reductase via a hydroquinone; Tanaka H et al.; Nanaomycin D reductase which is involved in the biosynthesis of the antifungal antibiotic nanaomycin catalyzes the formation of nanaomycin A from nanaomycin D in the presence of NADH under anaerobic conditions . On the other hand, under aerobic conditions NADH is consumed and nanaomycin A formation is markedly reduced . These findings suggest that nanaomycin A synthesis is not due to the direct reduction of the 5-membered lactone ring of nanaomycin D . Reduction of various quinones by the enzyme was examined . It was found that nanaomycin A is converted to its hydroquinone derivative in the presence of NADH under anaerobic conditions, whereas NADH consumption alone is observed under aerobic conditions . When p-benzoquinone, 1,4-naphthoquinone or menadione is used instead of nanaomycin D, NADH is also consumed . These results indicate that: (1) these compounds act as electron acceptors, (2) O2 functions as final electron acceptor under aerobic conditions, and (3) nanaomycin D reductase is, in fact, an NADH dehydrogenase (quinone) . Changes in the UV-absorption spectrum of a reaction mixture containing nanaomycin D and NADH indicate that a hydroquinone derivative is formed as an intermediate during nanaomycin A formation . Similar results were obtained when nanaomycin D is reduced chemically with NaBH4 or Zn powder . It was concluded that nanaomycin D is converted to a hydroquinone derivative and that nanaomycin A is then formed nonenzymatically through intramolecular electron transfer.

Mol Biol (Mosk), 1982 Nov-Dec, 16(6), 1245 - 52
{Physico-chemical properties of the complexes of bacitracin with DNA and its effect on the process of transcription in vitro}; Permogorov VI et al.; The aim of the present paper was to study the action of one of the peptide antibiotics, bacitracin, as the regulator of gene activity at the transcription level . Therefore the commercial bacitracin has been fractionated into two main parts by paper chromotography . These two fractions have been identified as bacitracin A (biologically active) and bacitracin F (biologically inactive) . The binding of both fractions to DNA has been studied . It has been shown that bacitracin A stabilizes DNA to a lesser degree than bacitracin F does . DNA-bacitracin complexes are formed in the major groove of the DNA helix by hydrogen bonds . The analysis of the the obtained experimental data allows us to suppose that bacitracin binding to DNA has a very specific character and that this antibiotic may act as the regulator of gene activity.

Klin Padiatr, 1982 Nov-Dec, 194(6), 409 - 11
{Chronic benign neutropenia}; Speer C et al.; In four patients we found a benign chronic neutrocytopenia . They suffered from recurrent infections of the mouth and pharynx region and the upper airway . Furthermore pyogenic skin infections and a lymphadenitis were seen . With the exception of a maturity arrest of the myelopoiesis in the bone marrow there were no hematologic abnormalities . Antibiotic therapy was necessary only during periods of acute infections . As long as there is no consistent terminology we propose to subsume this syndrome under the name benign chronic neutrocytopenia.

J Pediatr Ophthalmol Strabismus, 1982 Nov-Dec, 19(6), 326 - 8
Congenital eversion of the eyelids: a report of two cases treated with conservative management; Moainie R et al.; Congenital eversion of the upper eyelids is rare . Most previous cases were associated with Down's Syndrome, difficult labor and delivery, or underlying skin disorders . The two present cases occurred in normal patients with unremarkable deliveries . They responded promptly to conservative treatment, including use of a horizontal grid of tape on each lid, which successfully repositioned the lids and facilitated instillation of antibiotic solutions.

Foot Ankle, 1982 Nov-Dec, 3(3), 142 - 9
Hoffman procedure in the ulcerated diabetic neuropathic foot; Jacobs RL; Twelve diabetic patients with varying degrees of insensitivity of the foot presented with problems of forefoot ulceration beneath one or more metatarsal heads . This was associated with local abscess formation . Some of these patients had previously been subjected to surgical procedures such as ray resection or single metatarsal head resection for earlier problems and were left with areas of increased pressure in the weightbearing surface of the forefoot . Appropriate antibiotic therapy was started by the Infectious Diseases service in each case . Blood flow to the extremity was evaluated by pulse volume recordings and measurement of Doppler pressures at various levels down the extremity . Vascular reconstruction was indicated in two of these patients . After this reconstruction, circulation was deemed adequate to perform the Clayton (Clayton, M.L.: Surgery of the forefoot in Rheumatoid Arthritis . Clin . Orthop . 16:136-140, 1960) modification of the Hoffman (Hoffman, P.: An operation for severe grades of contracted or clawed toes . Am . J . Orthop . 9:441-449, 1911) procedure . This procedure was also done on 10 other patients with more adequate circulation . Although the time of healing was prolonged in some instances, all feet healed and the patients were successfully graduated to full weightbearing with extra depth shoes with soft neoprene rubber insoles . This procedure should be considered instead of transmetatarsal amputation in some patients with problems of ulceration and abscess formation of the forefoot if circulation is adequate, or can be restored to adequate levels by vascular reconstruction.

Laryngoscope, 1982 Nov, 92(11), 1269 - 73
Acute suppurative thyroiditis in children; Taylor WE Jr et al.; The ability of the thyroid gland to withstand infection is a well known phenomenon . In this regard, inflammatory disease of the thyroid gland in children is an uncommon occurrence . The frequency with which this proceeds to abscess formation is rare . Review of the literature of the past 25 years reveals only 21 reported cases of acute suppurative thyroiditis in children, only one of which has been reported in the otolaryngologic literature . We report two cases of thyroid abscess in children initially presented as painful swellings in the lower neck . An overview of the management of these patients is detailed, including a discussion of the appropriate utilization of diagnostic studies . Demonstration of an internal fistula originating from the pyriform sinus underscores the need to consider a fourth branchial arch remnant as a possible source of infection . The importance of obtaining appropriate bacterial, fungal, and acid-fast cultures is stressed, as is the role of antibiotic therapy and definitive surgery once the diagnosis of thyroid abscess is made.

Ann Intern Med, 1982 Nov, 97(5), 717 - 9
Human brucellosis caused by Brucella canis: clinical features and immune response; Polt SS et al.; Human infection by Brucella canis is not often recognized due to a lack of serious consideration of the disease as a diagnostic possibility . Another factor is the limited availability of specific serologic tests needed in the absence of cross-reactivity between antibodies to B . canis and other Brucella pathogenic to humans . In addition, the organism may not be isolated from blood culture, particularly after antibiotic therapy . We report clinical and laboratory features of four patients with serologically diagnosed B . canis infection and point out the importance of specific serologic testing for B . canis when brucellosis is a diagnostic possibility.

J Fam Pract, 1982 Nov, 15(5), 895 - 7
Obstructive epiglottitis in adults; Guillozet N et al.; Acute epiglottitis, considered primarily a disease of infancy and early childhood, is seen rarely in adulthood but may be increasing in incidence . Although it may appear more slowly in adults, it is imperative to establish a rapid diagnosis and promptly assure care for this life-threatening disease . Epiglottitis may cause total obstruction of the upper airway, and it often falls to the primary care physician to discriminate this disease from the many self-limiting infections of the upper airway . The diagnosis should be considered if dysphagia and sore throat are not accompanied by hoarseness . Management of the airway is the first priority, but intravenous antibiotic use is justified.

J Clin Invest, 1982 Nov, 70(5), 1074 - 80
Hydration of sickle cells using the sodium ionophore Monensin . A model for therapy; Clark MR et al.; Mean cell hemoglobin concentration (MCHC) is thought to have an important influence in sickle cell disease, both through the strong dependence of sickling rates on hemoglobin S concentration, and through the profoundly limiting effect of high MCHC on the rheologic competence of oxygenated, irreversibly sickled cells (ISC) . Recent studies have tested the ability of antidiuretic hormone to reduce sickle cell MCHC by reducing plasma sodium (Na) and osmolality . An alternative means of reducing MCHC is to elevate intracellular cation content, rather than to depress extracellular cation concentration . In an effort to do this, we have treated sickle cells with Monensin, an antibiotic that selectively enhances membrane Na permeability . At submicromolar concentrations, Monensin substantially reduced the MCHC of whole sickle blood and isolated ISC, causing an improvement in cell deformability . Monensin's effectiveness in producing a controlled increase in erythrocyte water content suggests that agents that selectively increase membrane Na permeability could be therapeutically useful.

Ann Surg, 1982 Nov, 196(5), 518 - 24
Evaluation of splenic embolization in patients with portal hypertension and hypersplenism; Alwmark A et al.; Twenty-five patients with hypersplenism caused by portal hypertension were treated by repeated partial splenic embolization . Fourteen surviving patients were followed for up to six years showing a good response on peripheral blood count and bleeding tendency . Three patients died in connection with the treatment and another eight died within half a year because of the underlying liver disease . The discomfort and complications of fever, pain, pleural effusion, and abscess formation and the possibility to avoid these by repeated partial embolization under antibiotic cover are discussed . The results are compared with reports in the reviewed actual literature and the splenic embolization is given a place among the means of a successful selective symptomatic treatment of partial hypertension.

Am J Hematol, 1982 Nov, 13(3), 189 - 98
The treatment of acute myelocytic leukemia in patients 30 years of age and younger; Preisler HD et al.; The treatment of acute myelocytic leukemia in childhood and young adults has lagged behind that for acute lymphocytic leukemia . The studies described here were directed towards evaluating the role of intensive chemotherapy in the treatment of this illness . Intensive remission induction therapy combining cytosine arabinoside with an anthracycline antibiotic produced a complete remission rate comparable to that achieved in acute lymphocytic leukemia (45 of 49 patients or 92%) . Intensive consolidation chemotherapy produced a median duration of complete remission of 160 weeks with 40% of patients projected to be in remission at 4 years . By contrast, the median duration of remission for patients treated with moderate consolidation/maintenance therapy was 23 weeks with only 10% of patients in remission at 4 years . These studies demonstrate that intensive chemotherapy can be administered to pediatric patients and young adults and that this approach to therapy produces a high remission rate with a 3 year median duration of remission.

J Bacteriol, 1982 Nov, 152(2), 865 - 73
Asparagine-linked carbohydrate does not determine the cellular location of yeast vacuolar nonspecific alkaline phosphatase; Clark DW et al.; The nonspecific alkaline phosphatase of Saccharomyces sp . strain 1710 has been shown by phosphatase cytochemistry to be exclusively located in the vacuole, para-Nitrophenyl phosphate-specific alkaline phosphatase is not detected by this procedure because the activity of this enzyme is sensitive to the fixative agent, glutaraldehyde . To determine whether the oligosaccharide of nonspecific alkaline phosphatase is necessary to transport the enzyme into the vacuole, protoplasts were derepressed in the absence or in the presence of tunicamycin, an antibiotic which interferes with the glycosylation of asparagine residues in proteins . The location of the enzyme in the tunicamycin-treated protoplasts, as determined by electron microscopy and subcellular fractionation, was identical to its location in control protoplasts . In addition, carbohydrate-free alkaline phosphatase was found in vacuoles from tunicamycin-treated protoplasts . Our findings indicate that the asparagine-linked carbohydrate moiety does not determine the cellular location of the enzyme.

Am J Kidney Dis, 1982 Nov, 2(3), 354 - 6
Occult dental infection causing fever in renal transplant patients; Wilson RL et al.; Fever secondary to odontogenic infection following successful renal transplantation is reported in three patients . All three patients initially lacked signs or symptoms localizing to the oral cavity, and two of the three patients did not have x-ray evidence of abscess formation . Two patients received antibiotic therapy without any apparent clinical response, and all three patients responded promptly to surgical extractions . Our patients illustrate that fever can be the only sign of dental sepsis in renal transplant recipients, and tooth extraction as empiric therapy may be necessary . Most important, however, is that the dental pathology responsible for their fever could have been detected and treated prior to transplantation . We recommend pretransplant dental evaluation of all patients with extraction of partially impacted molars and treatment of all periodontal disease and dental caries.

Biochemistry, 1982 Oct 12, 21(21), 5316 - 23
Revertants of a Chinese hamster ovary cell mutant resistant to suppression by an analogue of cholesterol: isolation and partial biochemical characterization; Chang TY et al.; A highly efficient selection procedure was developed for isolating revertants of Chinese hamster ovary (CHO) cell mutants resistant to suppression by 25-hydroxy-cholesterol . The procedure is based on the fact that the specific polyene antibiotic amphotericin B caused a lethal porous complex formation with membrane cholesterol only in cholesterol-rich cells . The wild-type cells and the revertant cells switched to grow from fetal calf serum medium to delipidated fetal calf serum medium for approximately 1 day became deficient in cellular cholesterol content . These cells, unlike the cholesterol-rich mutant cells, became much less sensitive to amphotericin B cytotoxicity . The spontaneous reversion frequency of a previously reported 25-hydroxycholesterol-resistant cell clone, 25-RA {Chang, T.-Y., & Limanek, J.S . (1980) J . Biol . Chem . 255, 7787-7795}, was found to be approximately 3 X 10(-6), a frequency comparable to other single gene mutations of CHO cells . Biochemical analyses of three of these revertants showed that all defects manifested in 25-RA cells reverted back in parallel, a result suggesting that these observed defects in 25-RA cells are due to a single mutation event, thus supporting the hypothesis (Chang & Limanek, 1980) that a common controlling factor may be involved in mediating the suppressive action(s) of the cholesterol analogue on various cholesterogenic enzyme activities . The function of this common controlling factor is rendered abnormal in 25-RA cells by mutation.

Nucleic Acids Res, 1982 Oct 11, 10(19), 6207 - 19
Studies on the inhibition of repair of ultraviolet- and methyl methanesulfonate-induced damage in the DNA of human fibroblasts by novobiocin; Snyder RD et al.; The antibiotic novobiocin is shown to alter the sedimentation properties of human cellular DNA in alkaline sucrose . This alteration is at least partially due to increased DNA-protein binding in the cell in the presence of novobiocin . Pyrimidine dimer analysis and repair replication studies support previous reports that novobiocin inhibits repair of UV damage in human cells but we find this block to be shortlived . It is also shown that novobiocin is ineffective at blocking "long-patch" repair induced by methyl methanesulfonate as measured both by CsCl density centrifugation and the ara-C inhibition technique . However, the accumulation of breaks in MMS-treated cellular DNA in the presence of novobiocin suggests that some "short-patch" alkylation repair may be inhibited by the antibiotic . These findings are discussed in light of the proposal that novobiocin may inhibit a DNA gyrase-like activity in human as in bacterial cells.

Antibiotiki, 1982 Oct, 27(10), 779 - 81
{Cytostatic action of semisynthetic rubomycin derivatives}; Volkolupova OP et al.; The cytostatic effect of some semi-synthetic derivative of rubomycin, an antitumor antibiotic, was studied with two methods, i.e . the method of spectrophotometric determination of the increase of the total amount of nucleic acids and the radiometric method based on measuring the intensity of incorporation of labeled thymidine . The results obtained with the two methods were similar . 9 semi-synthetic derivatives of rubomycin were studied with respect to the tumor cells NK/Li . The cytostatic effect of 8 out of these derivatives was 2-170 times lowers than that of rubomycin . The cytostatic effect of N-ethylrubomycin was equal to that of the initial antibiotic.

Antibiotiki, 1982 Oct, 27(10), 776 - 8
{Role of age in the interaction of tetracycline with the subcellular fractions of rat liver homogenate}; Guliaev AE et al.; The effect of the rat age on the binding of tetracyclines to the subcellular fractions of liver homogenates was studied . The tetracyclines significantly lost their activity after the contact with the cell organoids . The level of the binding was lower in the newborn and old rats, the complex of tetracycline with mitochondria being less stable . The greater part of the antibiotic reduced its activity after washing of the organoids . The deposition of the antibiotics in the cells was the most pronounced in the pubertal animals.

Antibiotiki, 1982 Oct, 27(10), 753 - 7
{Effect of mass exchange conditions on the biosynthesis of oxytetracycline}; Maksimova EA et al.; An increase in the power input for agitation from 0.4 to 2.7 kw/m3 in oxytetracycline biosynthesis stimulated the antibiotic production due to an accelerated use of carbohydrate and nitrogen and an earlier transition of the culture to the phase of the antibiotic biosynthesis . The procedure for determination of the aeration and agitation conditions by the maximum rate of the oxygen uptake is described . The procedure is recommended for the use in the studies on determination of such conditions for the biosynthesis of of oxytetracycline in large apparatus.

Urology, 1982 Oct, 20(4), 454 - 7
Seminal vesiculography: limited value in vesiculitis; Dunnick NR et al.; Seminal vesiculograms were performed on 44 men being evaluated for chronic perineal pain consistent with seminal vesiculitis . The vesiculograms were performed prior to antibiotic instillation into the vas deferens . Vesiculograms were abnormal in 32 of the 44 patients (73%) . The most common abnormality was the presence of multiple small diverticula producing a feathery appearance of the vas deferens (64%), a finding present in only 19 per cent of patients being evaluated for infertility and 20 per cent of normal patients . Asymmetry and incomplete filling of the seminal vesicles were less common abnormalities . Seventeen of these patients had seminal vesiculectomies for persistent or recurrent pain, and 15 have been followed long enough to assess the results . The histologic examination of the excised seminal vesicles was abnormal in only 3 patients (20%), despite radiographic abnormalities in 10 (67%) and improvement after surgery in 12 (80%) . Seminal vesiculography may be useful to exclude anatomic abnormalities prior to instillation, but does not appear sufficiently specific to warrant use as the primary diagnostic examination for patients suspected of having seminal vesiculitis.

Int J Clin Pharmacol Ther Toxicol, 1982 Oct, 20(10), 447 - 53
Pharmacokinetics of amoxicillin in subjects with normal and impaired renal function; Arancibia A et al.; The pharmacokinetics of amoxicillin was investigated in 4 healthy volunteers and in 16 patients with varying degrees of renal impairment, 4 of whom were on regular hemodialysis . Amoxicillin was administered both in a 1-g single intravenous injection and two 500-mg capsules per os . The kinetics of the antibiotic followed an open two-compartment model . In the patients with renal failure there was a significant decrease in beta, kappa10, and total body clearance . A linear relationship between beta of amoxicillin and creatinine clearance was found . This relationship allows dosage regimen adjustment for patients with renal impairment . A significant increase in the absorption half-life of the antibiotic was also observed in patients with renal impairment . The half-life of the antibiotic during hemodialysis was 2.3 h.

Clin Orthop, 1982 Oct, (170), 56 - 61
Revision surgery in total hip arthroplasty: surgical technique and results; Wroblewski BM; Revisions in failed total hip arthroplasty have produced some good results . In cases of stem fracture, the problem is lack or loss of proximal support in the presence of distal fixation of the stem . This aspect must be borne in mind during primary and revision surgery . Routine use of long intramedullary stems has little to commend it . Proximal support of the stem is essential . In revision for deep sepsis, antibiotic-loaded cement has increased the success rate . Sound component fixation is, however, of paramount importance . If success is to be achieved in revision surgery, the patients at risk must be carefully followed up by serial radiographs . The timing of the revision will depend on awareness of the problem rather than the patients' symptoms . This, at times, may mean revising early and for radiographic changes alone if the quality of the bone stock is to be preserved, and if the chances of success are to be improved.

Ann Emerg Med, 1982 Oct, 11(10), 549 - 52
Retropharyngeal abscess; Hamer R; Two cases of retropharyngeal abscess are presented . The first case, that of a 4-year-old boy, was classical, diagnosed early, and treated with prompt incision and drainage . The second case was that of a 51-year-old man who developed complete upper airway obstruction, pneumothorax, and congestive heart failure prior to surgical drainage . These cases are presented to remind emergency physicians of this formidable entity and of the need for constant vigil in the management of this life-threatening pre-antibiotic relic.

J Nucl Med, 1982 Oct, 23(10), 878 - 82
Effect of bolus composition on esophageal transit: concise communication; Fisher RS et al.; The technique of esophageal scintigraphy was developed as a sensitive, quantitative, noninvasive test of esophageal transit . Esophageal scintigraphy was performed in 40 asymptomatic normal volunteers in order to determine the effect on esophageal transit of the following: body posture (sitting vs . supine), liquid vs . solid, the solid being either a standard #4 gelatin capsule of the size used for antibiotic capsules, or a cube of solid food such as cooked chicken liver . The results showed that liquids emptied completely from the esophagus after one swallow, whether supine or sitting . Capsules or liver cubes, when ingested without water, frequently remained in the esophagus for up to two hours without the subject's having any sensation that the solid had not left the esophagus . Both capsules and liver cubes cleared the esophagus better in the upright than in the supine position . When gelatin capsules were swallowed with as little as 15 ml of water, but after a preliminary sip of water, there was complete transit in each case . The study suggests that the practice of assisting patients into a sitting position and instructing them to take a sip of water before attempting to swallow a capsule will assure better transit of the capsule even when swallowed with as little as 15 ml of water . This may reduce the incidence of esophagitis following oral antibiotics, and of esophageal erosions from aspirin-containing medications.

Cancer Res, 1982 Oct, 42(10), 4210 - 4
Adenine phosphoribosyltransferase deficiency in cultured mouse mammary tumor FM3A cells resistant to 4-carbamoylimidazolium 5-olate; Koyama H et al.; 4-Carbamoylimidazolium 5-olate (CIO), the aglycone of the nucleoside antibiotic, bredinin (4-carbamoyl-1-beta-D-ribofuranosylimidazolium 5-olate), exhibited potent cytotoxic effects of subclonal line F28-7 of C3H mouse mammary carcinoma FM3A cells in culture . We isolated 11 cell lines resistant to CIO from wild-type F28-7 cells mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine . These resistant (cio') lines were 160- to 400-fold less sensitive to CIO than were the wild-type cells and inherited the resistant phenotypes during subculture for more than 3 months in the drug-free medium . They were cross-resistant to an adenine analog, 2,6-diaminopurine, while 2,6-diaminopurine-resistant (dap') lines, isolated independently, were cross-resistant to CIO . Neither of the cio' lines tested were able to form colonies in agar medium containing azaserine and adenine, nor were they able to incorporate tritiated adenine into the macromolecular fraction, indicating that they could not utilize exogenous adenine for growth . Enzyme assays using cell-free extracts revealed that all the cio' lines had undetectable levels of adenine phosphoribosyltransferase (EC 2.4.2.7) activity, but they, except one, had normal levels of hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) and adenosine kinase (EC 2.7.1.20) activities . These results demonstrate that the CIO resistance in these lines is attributed to deficient adenine phosphoribosyltransferase activity and therefore that CIO is activated by adenine phosphoribosyltransferase to form a cytotoxic nucleotide within the drug-sensitive cells.

J Bacteriol, 1982 Oct, 152(1), 89 - 97
Genetic transformation of Rhodopseudomonas sphaeroides by plasmid DNA; Fornari CS et al.; A broad-host-range cloning vector, pUI81, was constructed in vitro from plasmids RSF1010 and pSL25 (a pBR322 derivative) and used to assay for transformation in Rhodopseudomonas sphaeroides . Washing cells with 500 mM Tris was an effective means of inducing competence for DNA uptake . Transformation frequencies as high as 10(-5) (transformants per viable cell) have been achieved by incubating Tris-treated cells with plasmid DNA, 100 mM CaCl2, and 20% polyethylene glycol 6000 . Maximum frequencies were obtained when recipient cells were spread onto selective media after a 6.5-h outgrowth period in antibiotic-free medium . The structure (open circular versus closed, covalent circular), size, and concentration of plasmid DNA all significantly affected the transformation frequency . Four different plasmids, all small and suitable as cloning vectors, have been introduced by transformation into several different R . sphaeroides strains . Recombinant DNA carried on small, nonconjugative plasmids with broad host ranges can now be directly transferred to R . sphaeroides by this method.

Chir Ital, 1982 Oct, 34(5), 830 - 5
{Anatomo-pathologic and therapeutic considerations on the Papineau method}; Caserta S et al.; The authors study the treatment of bone infections through Papineau's technique, and emphasize the element they consider essential in the process restoring the loss of substance: the "bouton" according to the French School . On the basis of the experience deriving from the treatment of 22 patients, they subsequently point out the importance of local antibiotic therapy and, on the contrary, the inefficacy of the administration of antibiotics by general way, at least as far as the not strictly surgical period is concerned.

Am J Vet Res, 1982 Oct, 43(10), 1763 - 6
Effects of oral and injectable tetracyclines on bacterial drug resistance in feedlot cattle; Stabler SL et al.; Enteric bacteria isolated from feedlot heifers treated with tetracyclines (TET) were examined for resistance to TET and ampicillin . The effects of feeding (45 days) therapeutic and subtherapeutic quantities of chlortetracycline (CTC) and the injection of therapeutic doses of oxytetracycline (3 daily doses) were compared . Performance data from the 45-day trial did not identify an antibiotic effect on average daily gain, although cattle fed subtherapeutic quantities of CTC showed improved feed efficiency . Bacterial resistance to TET was increased in the heifers given the therapeutic and subtherapeutic quantities of CTC in the ration . However, an increase in resistance to ampicillin did not occur . Oxytetracycline injections had a short-term effect, increasing the number of resistant organisms only during the week of drug administration.

Ann Thorac Surg, 1982 Oct, 34(4), 422 - 6
Intrauterine cardiothoracic surgery: the fetal lamb model; Turley K et al.; We have developed fetal lamb models of congenital cardiothoracic lesions that have been allowed to progress through birth for physiological study . Simulated lesions, simulated repairs, actual lesions, and actual repairs have been performed in this model . Sixty-two fetal lambs comprised the study group, including 48 in which models were created and 14 controls . Models included pulmonary stenosis, aortic stenosis, and diaphragmatic hernia . Gestational age ranged from 90 to 120 days (0.6 of normal gestation) . In each pregnant ewe, laparotomy and hysterotomy were performed under general anesthesia, with care taken to avoid placental vessels . The foreleg was exposed, the appropriate anterior chest wall was isolated, and a thoracotomy was done . Thoracic or cardiac procedures then were performed under controlled transplacental anesthesia and perfusion . Following completion of the procedure, the fetal thoracotomy was closed, sterile antibiotic solution was placed in the amniotic sac, and the hysterotomy and laparotomy were closed . Subsequently the fetus either was allowed to progress to birth and infant study or underwent subsequent intrauterine repair and then was allowed to progress to birth and neonatal study . This fetal lamb model provides reproducible anatomical and pathophysiological lesions to facilitate the development of techniques for repair of such lesions in early infancy . Further, it offers the potential for developing methods of intrauterine cardiothoracic surgical repair.

Lab Anim, 1982 Oct, 16(4), 361 - 3
Noma in Saguinus oedipus: a report of 2 cases; Brack M; 2 cases of noma in cotton topped marmosets (Saguinus oedipus) are reported . The condition did not respond to antibiotic therapy, but was successfully treated in one animal by local application of ethacridine lactate.

Int J Clin Pharmacol Ther Toxicol, 1982 Oct, 20(10), 493 - 6
The kinetics of cefuroxime in ascitic and pleural fluid; Lechi A et al.; Adequate drug concentration at the infection site is a very important objective of antibiotic therapy . In this study we investigated the pharmacokinetics of the new methoximine, cefuroxime, in peritoneal and pleural fluids in 16 patients . After a 1-g dosage of cefuroxime, its concentration reaches a peak in ascitic fluid within 4-5 h . With a 2-g dose the peak level is reached in 2-3 h . After 5 h, cefuroxime concentration in ascites exceeds that in serum . Cefuroxime diffuses readily into the peritoneal space, where high concentrations (8-10 mcg/ml) are maintained for at least 6 h . Data on the kinetics in pleural fluid also seem to show high antibiotic diffusion rates, even if concentrations are never as high as those in blood at the same time following 1 g i.v . These favorable kinetic properties are probably due to low serum protein binding and to slow renal excretion.

Obstet Gynecol, 1982 Oct, 60(4), 502 - 5
Cephalothin prophylaxis for midtrimester abortion; Spence MR et al.; A randomized prospective double-blind study was conducted to determine the efficacy of prophylactic antibiotics as compared with placebo in 198 women undergoing second-trimester intraamniotic injection abortions . Patients received either sodium cephalothin or placebo intravenously before the procedure and for up to 8 additional doses . In 11 patients postabortion endometritis developed; 2 had received the antibiotic and 9 had received a placebo (P less than .05) . Prophylactic cephalothin decreased the incidence of endometritis in patients undergoing midtrimester injection abortion . An injection-abortion interval greater than 24 hours appears to identify patients at risk for the development of postabortion endometritis.

Antibiotiki, 1982 Oct, 27(10), 749 - 53
{Effect of various carbon and nitrogen sources on the biosynthesis of ristomycin, protease and pigments by a culture of Nocardia fructiferi var . ristomycini}; Toropova EG et al.; The effect of various sources of carbon and nitrogen on the biosynthesis of ristomycin, protease and pigments by Nocardia fructiferi was studied . It was shown that the carbon sources had the most significant effect on the biosynthesis of the antibiotic . The maximum biosynthetic activity of the Nocardia was observed in the medium containing 1-2 per cent of soybean meal and 2 per cent of glycerol . Under such conditions all the three biologically active substances formed . The contents of ristomycin, protease and pigments amounted to 562-649 microgram/ml, 26-30 PU/ml and 0.45-0.63 conditional units, respectively.

Pflugers Arch, 1982 Oct 1, 394(4), 287 - 93
Poorly selective cation channels in the skin of the larval frog (stage less than or equal to XIX); Hillyard SD et al.; The abdominal skin of bullfrog larvae (Rana catesbeiana) was placed in an Ussing-type chamber, and its transepithelial electrical parameters were recorded with mucosal solutions of different ionic composition . With "K+-like" cations (K+, NH+4, RB+, Cs+) the power spectra of the fluctuations in short-circuit current displayed a Lorentzian component (fc = 30 - 40 Hz) . The relaxation noise could be suppressed by addition of the K+ -channel blockers Ba2+ and TEA to the mucosal solution . Also, in presence of the ionophore antibiotic nystatin the Lorentizian noise was abolished . The Na+ -channel probes amiloride and benzimidazolyl-2-guanidine (BIG) both enhanced the relaxation noise obtained with the K+-like cations but, with Na+ and Li+, also caused the rise of a relaxation component above the background noise . In presence of amiloride or BIG, the addition of Ba2+, TEA and nystatin still abolished the Lorentizian noise . It can be concluded that the relaxation-noise source is located in the apical cell membranes of the tadpole skin . These spontaneously fluctuating cation channels do not seem to strictly discriminate between K+-like ions (K+, NH+4, Rb+, Cs+) and Na+-like ions (Na+, Li+) . On the other hand, well-known specific probes for K+ channels (Ba2+, TEA) and for Na+ channels (amiloride, BIG) interact with this apical cation channel . It is possible that the poorly selective channel plays a role in the ontogenesis of the specific Na+ transport in the maturing frog skin.

Arch Intern Med, 1982 Oct, 142(10), 1934 - 5
Apparent ketoconazole failure in candidal cholecystitis; Brooks BJ Jr et al.; Fungal acalculous cholecystitis is a rarely recognized complication of disseminated candidal infections . We report such a case of systemic candidiasis that developed in a man who was diabetic while he was receiving broad-spectrum antibiotic therapy for an infected foot ulcer . Ketoconazole, a new imidazole antifungal agent, was used successfully to treat the systemic candidal infection but it failed to eradicate the fungus in the biliary tract.

J Bacteriol, 1982 Oct, 152(1), 338 - 44
Antagonism of the B subunit of DNA gyrase eliminates plasmids pBR322 and pMG110 from Escherichia coli; Wolfson JS et al.; The constructed plasmid pBR322 and the native plasmid pMG110 were eliminated (cured) from growing Escherichia coli cells by the antagonism of the B subunit of the bacterial enzyme DNA gyrase . The antagonism may be by the growth of cells (i) at semipermissive temperatures in a bacterial mutant containing a thermolabile gyrase B subunit or (ii) at semipermissive concentrations of coumermycin A1, an antibiotic that specifically inhibits the B subunit of DNA gyrase . The kinetics of plasmid elimination indicate that plasmid loss occurs too rapidly to be explained solely by the faster growth of that plasmid-free bacteria and, therefore, represents interference with plasmid maintenance.

J Immunol, 1982 Oct, 129(4), 1594 - 9
Amphotericin B alters the affinity and functional activity of the oligopeptide chemotactic factor receptor on human polymorphonuclear leukocytes; Lohr KM et al.; Leukocyte chemotaxis is initiated by the binding of chemotactic factors to specific, high-affinity receptors . Amphotericin B, a polyene antibiotic that binds to membrane cholesterol, inhibits human neutrophil (PMN) chemotaxis . We examined the effects of this drug on PMN functions mediated by the oligopeptide chemotactic factor receptor . The antibiotic irreversibly inhibited chemotaxis and depressed the binding of the radiolabeled chemoattractant, fMet-Leu-{3H}Phe, to its receptor without affecting the receptor's specificity . The drug lowered the binding affinity of the receptor by up to fivefold and slightly increased its number . Doses of amphotericin B that depressed receptor affinity and inhibited chemotaxis did not diminish lysosomal enzyme secretion or superoxide anion production . Nystatin, a less potent polyene antibiotic, also diminished chemotactic factor binding, but to a lesser degree than amphotericin B did . A chemically unrelated antifungal agent had no effect on either binding or chemotaxis . Thus, pharmacologic manipulation can alter the affinity of the chemotactic factor receptor on human PMN; this alteration is associated with a change in receptor function . The data suggest that receptor affinity regulates or at least reflects its functional state, and that the transduction mechanisms for various biologic responses mediated by the chemoattractant receptor are heterogeneous . By pharmacologic alterations of receptor affinity, one may be able to modulate specific biologic responses elicited by chemoattractant receptor-ligand interactions.

Oral Surg Oral Med Oral Pathol, 1982 Oct, 54(4), 396 - 400
Management of the dental patient receiving corticosteroid medications; Kalkwarf KL et al.; Patients who have undergone therapy with glucocorticoids present unique problems for the dentist . Persons currently receiving steroid therapy have altered responses to infection and wound healing . More important, many patients who are taking or have taken glucocorticoids have a high risk of developing acute adrenal insufficiency when placed in a stressful situation . When treating patients with a history of glucocorticoid therapy, one must obtain precise information from the medical history to determine the relative risk of pituitary-adrenal suppression . If the patient is at risk, the dentist must determine the need for the following prophylactic measures: (1) systemic antibiotic therapy, (2) anxiety control, and (3) increased administration of glucocorticoids (steroid prep) . If a patient experiences adrenal crisis, the dentist must be capable of interpreting the signs and administering appropriate therapy.

Sem Hop, 1982 Sep 30, 58(35), 2008 - 10
{Prophylaxis of infectious complications in maxillo-facial surgery . Value of cefazolin . (A review of 400 cases)}; Peri G et al.; The value of short-term prophylaxis with antibiotics in maxillo-facial surgery and plastic facial surgery is studied . 200 patients were included in the study and compared to 200 controls who were given the usual systematic antibiotic therapy, with a different antibiotic, for more than 6 days . 400 case-reports were thus retrospectively analyzed . The results show that when the surgical procedure lasts for less than three hours, short-term prophylaxis with antibiotics is more effective than the usual systematic antibiotic therapy given for more than 6 days.

JAMA, 1982 Sep 17, 248(11), 1348 - 50
Fusobacterium necrophorum septicemia following oropharyngeal infection; Seidenfeld SM et al.; Fusobacterium necrophorum septicemia developed in five patients after an oropharyngeal infection . Four patients had sore throat or neck pain, and two had findings of jugular vein septic thrombophlebitis . Metastatic abscesses, including embolic pneumonia, empyema, septic arthritis, and osteomyelitis, also occurred . Four patients recovered and one died . Proper treatment requires recognition of the oropharyngeal source of the septicemia and its differentiation from endocarditis . Antibiotic therapy should be prolonged, and metastatic abscesses drained.

J Biol Chem, 1982 Sep 10, 257(17), 9887 - 90
Cerulenin blocks fatty acid acylation of glycoproteins and inhibits vesicular stomatitis and Sindbis virus particle formation; Schlesinger MJ et al.; Cerulenin, an antibiotic that inhibits de novo fatty acid and cholesterol biosynthesis, effectively inhibited the formation and release of virus particles from chicken embryo fibroblasts infected with Sindbis or vesicular stomatitis virus (VSV) . When added for 1 h at 3 h postinfection, the antibiotic blocked VSV particle production by 80 to 90% and inhibited incorporation of {3H}palmitic acid into the VSV glycoprotein by an equivalent amount . The effect of this antibiotic on virus protein and RNA biosynthesis was significantly less than that on fatty acid acylation . Nonacylated virus glycoproteins accumulated inside and on the surface of cerulenin-treated cells . These data indicate that fatty acid acylation is not essential for intracellular transport of these membrane proteins, but it may have an important role in the interaction of glycoproteins with membranes during virus assembly and budding.

Anesth Analg, 1982 Sep, 61(9), 767 - 70
Neuromuscular blocking effects of tobramycin, gentamicin, and cefazolin; Lippmann M et al.; Forty patients (A.S.A . class I or II), 18 to 75 years of age, who were undergoing elective surgery were studied to determine the clinical and subclinical neuromuscular blocking effects of two antibiotics, tobramycin and gentamicin and to compare these effects with those produced by cefazolin, an aminoglycoside not known to produce paralysis . Patients were prospectively and randomly assigned in approximately equal numbers to one of four groups: group A received 1 mg/kg of tobramycin; group B, 1 mg/kg of gentamicin; group C, 500 mg of cefazolin; or group D, control (no antibiotic) . Antibiotics were administered intravenously 45 minutes immediately preceding the study . The ulnar nerve was stimulated supramaximally and neuromuscular function was measured electromyographically . Anesthesia was induced with thiopental, 4 mg/kg IV, and maintained with endotracheal enflurane 1.0% to 1.5% (inspired) and N2O-O2 (2 L:1 L) after intubation . Succinylcholine (1 mg/kg) was administered after induction of anesthesia and the magnitude and duration of neuromuscular block monitored . d-Tubocurarine (0.1 mg/kg) was given 5 to 10 minutes after full recovery from succinylcholine and repeated as required . At the end of the operation, atropine, 0.02 mg/kg, and neostigmine, 0.4 mg/kg, were used to reverse the block . Base line neuromuscular data, duration of block of succinylcholine, and potency, duration of block, recovery rate, train-of-four fade, tetanic trend, response to double stimuli, post-tetanic effect, and reversibility of the subsequent d--tubocurarine-induced neuromuscular block were not significantly different (p less than 0.01) between any two groups . Tobramycin, gentamicin, and cefazolin, in recommended single doses, lack clinical neuromuscular blocking and subclinical relaxant-potentiating effects.

Vopr Med Khim, 1982 Sep-Oct, 28(5), 98 - 102
{Inhibition by cycloheximide of the incorporation of radioactive amino acids into nuclear matrix proteins of Zajdela ascites hepatoma}; Bul'diaeva TV et al.; Proteins of nuclear matrix readily incorporated labelled amino acids after incubation of ascites Zajdela hepatoma cells with 14C-hydrolyzate of chlorella proteins . Cycloheximide at the concentrations, inhibiting the cytoplasmic protein synthesizing system, significantly decreased the labelled amino acid incorporation both into nuclear proteins and into proteins of nuclear matrix but the antibiotic effect was less distinct in the matrix . The incorporation into proteins with molecular mass below 26 KD and above 150 KD was especially distinctly inhibited as shown in experiments on separation of the matrix proteins by means of SDS-polyacrylamide gel electrophoresis . Besides the inhibition of the incorporation of amino acids, a decrease in content was found in studies of the fraction of matrix low molecular proteins . The high rate of metabolism of nuclear matrix low molecular proteins is discussed.

No Shinkei Geka, 1982 Sep, 10(9), 933 - 8
{Problems of the chemotherapy for malignant brain tumors--treatment with granulocyte transfusion for refractory infection due to agranulocytosis}; Kokunai T et al.; Recent progress of the chemotherapy for malignant brain tumors has made some prolongation of survival time of the patient . However, it is still far away from our satisfactions and still we are even irritable about the results of brain tumor therapies in neurosurgical practice . One of the major side effects of these chemotherapeutic agents is myelosupression which is dose-dependent . When applying the chemotherapy to the brain tumor patients aggressively, we experience that occasionally we are having a chance to see the so-called "chemotherapy death" caused by agranulocytosis and severe infections . In this report we introduced the granulocyte transfusion by the method of filtration leukapheresis in the neurosurgical field, especially its technical aspects, its advantages, and its indications . And we presented a case of pontine glioma who had been successfully treated with the granulocyte transfusion for the agranulocytosis with serious infection . The indication of granulocyte transfusion are as follows: (1) The count of granulocyte is under 500/mm3 . (2) The patient has the infection that has no response to the intensive antibiotic therapy for about two days . The advantages of this method of granulocyte transfusion are as follows: (1) Low cost and simple process . (2) The contamination of lymphocyte is little . (3) A large number of granulocyte (1.93 X 10(10)) are obtained from one donor for about two hours . (4) Side effects to donor and patient are very few . We concluded hereafter that this method of granulocyte transfusion should be prepared broadly on the neurosurgical wards in cases of agranulocytosis during the chemotherapy for malignant brain tumors.

Pflugers Arch, 1982 Sep, 394(3), 243 - 9
Inhibition of the slow inward current and the time-dependent outward current of mammalian ventricular muscle by gentamicin; Hino N et al.; The aminoglycoside antibiotic, gentamicin (GM), depressed the plateau phase and shortened the duration of the action potential in guinea pig papillary muscle . Its effect on the membrane currents was studied by a single sucrose gap voltage clamp method . The slow inward current (is) was remarkably diminished by GM with little change in its time course, in the voltage-dependency of the steady-state inactivation and activation or in its reversal potential . The maximal amplitude of is, obtained by subtracting the Co2+-resistant current, was reduced to 57% by 0.1 mmol/l GM and almost reduced to zero by 1 mmol/l GM . The efficacy of GM in inhibiting (is) was reduced by increasing the external Ca2+ concentration from 1.8 to 5.4 or 10.8 mmol/l, but not by the application of adrenaline . The time-dependent outward current (ik) was also decreased by GM but only at higher concentrations . It is proposed that the depressant action of GM on is was due to a blockade of slow channels, whereby GM may have dislocated Ca from the binding sites at slow channels on the external surface of the membrane.

Jpn J Antibiot, 1982 Sep, 35(9), 2213 - 8
{Clinical experience of cefoxitin used for the prevention of postoperative infections in gastroenterological surgery}; Kitou M; A total of 16 hospitalized patients underwent surgery for gastroenterological problems in the Department of Gastroenterological Surgery, Kanazawa Medical College Hospital, during the period from April 1981 to September 1981 . After they had undergone partial or total gastroenterological resection, cefoxitin was administered for the prevention of postoperative infections . The following findings were obtained . 1 . Fifteen out of 16 patients responded well with the clinical efficacy of 94 percent . 2 . Elevations in S-GOT levels were noted in 3 patients . However, no other abnormalities were evident in the clinical data . 3 . These clinical results indicate that cefoxitin is an effective antibiotic for the prevention of postoperative infections in gastroenterological surgery.

Jpn J Antibiot, 1982 Sep, 35(9), 2159 - 62
{The whole body autoradiographic studies on the distribution of 14C-labelled sodium 7 beta-{(2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazine-carboxamido)-3-hydroxybutanamido}-7 alpha-methoxy-3-{(1-methyl-1H-tetrazol-5-yl)thiomethyl}-3-cephem-4-carboxylate (14C-T-1982) in mice}; Saikawa I et al.; The distribution of T-1982, a new semisynthetic cephamycin antibiotic, was studied with whole body autoradiography in normal male mice, pregnant mice and experimental pyelonephritic mice following a single intravenous administration of 80 mg/kg of 14C-T-1982 . 1 . In normal male mice, the radioactivity was distributed at high concentration in the liver, kidney, lung, gastrointestinal tracts, skin, salivary gland, tongue and muscle, but was hardly observed in the central nervous system that composed of the brain and spinal cord . 2 . In pregnant mice, the radioactivity was hardly observed in the fetuses . 3 . In experimental pyelonephritic mice, considerable radioactivity was concentrated on the acute inflammatory area.

South Med J, 1982 Sep, 75(9), 1063 - 6
Rocky Mountain spotted fever in pregnancy: differential diagnosis and treatment; Herbert WN et al.; Rocky Mountain spotted fever (RMSF) presents both diagnostic and therapeutic difficulties in the pregnant patient . Early clinical manifestations may be mistaken for normal pregnancy changes . Accurate diagnosis is essential, since several of the disorders in the differential diagnosis may have important obstetric implications . Antibiotics generally used to treat serious infections during pregnancy are ineffective in treating RMSF . Chloramphenicol is the antibiotic of choice . Specific recommendations for evaluating pregnant patients with suspected RMSF are given.

Laryngoscope, 1982 Sep, 92(9 Pt 1), 1006 - 15
Frontal sinus ablation for frontal osteomyelitis; Mohr RM et al.; Frontal sinusitis with frontal osteomyelitis is a potentially life threatening disease . Diagnostic and therapeutic errors occur frequently because of antibiotic masking of already silent frontal lobe complications or lack of suspicion on the part of the otolaryngologist or the neurosurgeon . Frontal sinus infection and/or trauma frequently require otoneuro cooperation for care . Four cases of complications of frontal sinus infection with osteomyelitis are discussed . Three had epidural empyemas and one had a subdural empyema with an anterior 1/3 superior sagittal sinus thrombosis and multiple brain abscesses . Each patient was approached through a frontal craniotomy and the frontal sinus posterior plate examined from behind . Each had posterior dehiscences . Follow-up of osteomyelitis requires multiple tests including computerized tomography, polytomography and possibly bone or gallium scans . Twenty year or more follow-up is essential.

Arch Otolaryngol, 1982 Sep, 108(9), 587 - 90
Replanting the severed auricle . An update; Bernstein L et al.; An updated method of replanting a severed auricle is reported . Management consists of early, meticulous replantation with minimal debridement; cooling of the auricle; low-dose heparin sodium; dextran 40; antibiotic coverage; and multiple stab incisions to relieve venous congestion . The regimen is based on experience with nine successfully replanted auricles.

J Biochem Biophys Methods, 1982 Sep, 6(4), 341 - 9
Quantitative estimate of unlabelled cordycepin in acid-soluble pool isolated from rat brain tissue after intraperitoneal injection of the inhibitor; Kuznetsov DA et al.; A technique for the quantitative estimation of intraperitoneally injected unlabelled cordycepin in an acid-soluble pool (ASP) isolated from rat brain tissue is suggested . It consists in consecutive chromatography of ASP on Dowex 1 X 8, Dihydroxyboryl = SP500 and Sephasorb-HP . The fraction containing 2'-deoxyriboadenosine and 3'-deoxyriboadenosine (cordycepin) has been isolated from brain tissue ASP of experimental animals after a cordycepin injection . 2'-Deoxyriboadenosine fraction has been isolated from tissue ASP of the control animals not subjected to an inhibitor injection . Brain tissue antibiotic content has been estimated by the difference in nucleoside quantity values (microM) in these two fractions (control/experiment).

Br J Oral Surg, 1982 Sep, 20(3), 200 - 2
Subcutaneous emphysema; Kullaa-Mikkonen A et al.; Swelling appeared in an eight-year-old girl after amalgam restoration . The swelling, subcutaneous emphysema, due to the presence of air in the connective tissue disappeared over a period of two days; no complications occurred . The clinical importance of subcutaneous emphysema is that the migration of air to the mediastinum can cause death . According to the literature, many dental and oral procedures can cause subcutaneous emphysema . Since it can cause many complications due to infection, prophylactic antibiotic therapy is necessary.

Proc Natl Acad Sci U S A, 1982 Sep, 79(17), 5166 - 70
Regulated expression of human interferon beta 1 gene after transduction into cultured mouse and rabbit cells; Canaani D et al.; The human interferon beta 1 gene has been inserted into simian virus 40 hybrid plasmid vectors carrying the bacterial phosphotransferase gene (neo), and introduced into cultured mammalian cells by DNA transfection . A majority of the transformants resistant to the antibiotic G418 were capable of synthesizing and secreting biologically active human interferon . The neo/interferon transformants contain several copies of the transfecting DNA integrated into cellular DNA sequences . In most transformants the production of human interferon and its mRNA is induced by the addition of poly(rI) X poly(rC); by contrast, the level of neo mRNA is not increased under the same conditions . The 5' end of the human interferon mRNA produced after induction was indistinguishable from the interferon mRNA induced in human fibroblasts . This indicates that information enabling human beta 1 interferon gene to be induced by poly(rI) X poly(rC) is localized to sequences within, or 5'-proximal to, the coding sequence.

Otolaryngol Head Neck Surg, 1982 Sep-Oct, 90(5), 534 - 9
Medical treatment of chronic sinusitis in the immunocompetent and immunosuppressed patient: a review; Rybak LP; Chronic sinusitis may arise from a variety of causes . Failure of mucociliary transport, nasal obstruction, and breakdown of the mucosal barrier are important mechanisms that may contribute to irreversible tissue pathologic changes in the paranasal sinuses . Diagnosis is usually made radiographically using plain films, polytomography, or computerized tomography . Medical treatment attacks underlying causes such as allergy or viscous mucus secretions . In addition to antibiotic therapy, management of the underlying medical problems, general prophylactic measures, immunologic reconstitution of specific immune deficiencies, and vaccine therapy when combined with surgical therapy are likely to help improve survival of the immunosuppressed patient with chronic sinusitis.

Toxicol Lett, 1982 Sep, 13(1-2), 105 - 12
Effect of cycloheximide on different stages of Drosophila melanogaster; Marcos R et al.; Cycloheximide, an antibiotic inhibiting protein synthesis, exerted a toxic effect on different developmental stages egg, larva and adult of Drosophila melanogaster . At the egg stage the early embryos were most sensitive . With larvae, a strong decrease in viability was found, with no sex difference . In adults, there was a dose-effect relationship, mortality increasing with concentration . At 10 and 15 mM, males were more sensitive than females . There were consistent differences between the control and cycloheximide-fed females in respect of the average number of eggs deposited and offspring produced.

Hautarzt, 1982 Sep, 33(9), 468 - 80
{Current status of drug therapy in male fertility disorders}; Schill WB; Recent advances in the medical treatment of male fertility disturbances by specific and empirical approaches are discussed . Specific approaches follow a pathophysiological concept and require critical patient selection . In contrast, empirical approaches do not allow patient selection, and a predictability of the success is not possible . Therefore, the response of the patients towards one of the available medical compounds has to be checked on an individual basis . Specific treatment includes replacement therapy of hormone-deficient men by human gonadotropins, inhibition of hyperprolactinemia by bromocriptine, antibiotic-antiinflammatory therapy of male genital tract infections and immunosuppressive treatment in cases of autoantibodies against spermatozoa . In addition, special medical approaches are available for disturbances of sperm transport and the retrograde ejaculation using sympathicomimetic or anticholinergic agents . Empirical treatment comprises the use of antiestrogens, human gonadotropins, androgens, kininogenases, and methylxanthines . As supporting therapy psychopharmacological compounds and spasmolytic agents should be mentioned here . The overall result of treatment is moderate . However, considering all possibilities of treatment conception rates between 30% and 50% will be obtained which differ from the spontaneous conception rates of between 10% and 20%.

Arch Mal Coeur Vaiss, 1982 Sep, 75(9), 1069 - 75
{Aortic insufficiency associated with ventricular septal defect and a coronary-right ventricle fistula after bacterial endocarditis: surgical correction of 3 lesions}; David M et al.; The authors report a case of Staph-aureus endocarditis on preexisting aortic incompetence . Two complications were observed during the course of the infection: ventricular septal defect, rare but classical, and coronary-right ventricular fistula, a complication not previously described to the best of the author's knowledge . Before the onset of endocarditis a continuous murmur had not been detected clinically or by phonocardiography . This sign appeared while the patient was receiving effective antibiotic therapy . The diagnosis, suggested by the clinical signs in a patient in cardiac failure, was confirmed by catheterisation . This type of complication, already described in peripheral vessels, may be understood when the extent of the lesions at the right coronary cusp, near the septum and right coronary ostium, are appreciated . A good surgical result was obtained due to early operation of the three lesions.

Ann Microbiol (Paris), 1982 Sep-Oct, 133(2), 335 - 41
{Attempt to obtain and maintain rumen entodiniomorph ciliates in axenic cultures}; Bonhomme A et al.; A method to obtain and maintain rumen ciliates in either axenic cultures or cultures with a reduced flora is described; it consists of two or three incubating periods with different antibiotic associations (separated by washing) and renewing of nutrient medium . On these conditions, Polyplastron multivesiculatum is obtained in an axenic state and can survive for 5 days . Entodinium sp . can survive for 10 to 14 days, but with a reduced bacterial population composed only of strict aerobic of facultative anaerobic species.

Gan To Kagaku Ryoho, 1982 Sep, 9(9), 1568 - 73
{Exploratory study of macromomycin}; Majima H; Macromomycin, a new antitumor antibiotic (NSC-170105) with significant antitumor activity in animal tumor systems, was administered to 18 patients in an exploratory study . The dose ranged from 1mg to 30 mg per body with a single dose was given . The toxic effects included delayed type leukopenia and thrombocytopenia with nadir of 4 weeks . Except mild upper GI disturbance, no pulmonary, cardiac, hepatic, renal or CNS toxicity was observed . No anaphylaxis was observed in this study . MTD of macromomycin considered to be 26 mg/m2 and optimal administration schedule will be 20 mg/m2 every 6 weeks . Antitumor activity was detected in one patient with ovarian carcinoma with MR in short period.

Stain Technol, 1982 Sep, 57(5), 273 - 82
Cytofluorometric determination of nuclear DNA in living and preserved algae; Hull HM et al.; Three DNA-localizing fluorochromes used in conjunction with epi (incident) UV illumination were examined for sensitivity and selectivity for the cytofluorometric determination of nuclear DNA in ten species of six algal genera: Mougeotia, Oedogonium, Sirogonium, Spirogyra and Zygnema among the green algae, and the marine red alga Polysiphonia boldii . In comparison with absorption photometry for the determination of nuclear DNA, the cytofluorometric procedure proved to be simpler and considerably more sensitive . Following staining with 4',6-diamidino-2-phenylindole (DAPI), nuclei fluoresce blue-white, the fluorescence intensity of the DNA-DAPI complex being considerably greater than that of the unbound dye molecule . Algal strains stained with 2,5-bis{4'-aminophenyl(1')}-1,3,4-oxadiazole (BAO) also showed brilliant blue-white nuclear fluorescence . Although the BAO schedule requires the use of freshly prepared dye and sulfite water, and careful control of hydrolysis, nuclear fluorescence of the stained specimens does not fade under irradiation of the UV beam as rapidly as it does with certain other fluorochrome procedures . A more useful fluorochrome was the fungal antibiotic mithramycin . Its staining schedule is simple and the bright orange-yellow fluorescence of the nuclei is associated with an exceptional degree of sensitivity and specificity for DNA . Forty-eight-year-old preserved filaments of Spirogyra jatobae, stained with either BAO or mithramycin, exhibited a fluorescence brilliance of nuclear and chloroplast DNA equal to that of fresh specimens of this species . The three schedules, but particularly the one with mithramycin, have proven useful in providing indirect evidence for variation in ploidy level in several of the above algal genera, and in verifying the assumed ploidy level of the gametophyte (haploid) and tetrasporophyte (diploid) of Polysiphonia boldii.

Cancer Lett, 1982 Sep, 16(3), 319 - 25
Effect of tunicamycin on receptors for tumor promoters; Solanki V et al.; A progressive decline in the specific binding of {20-3H}phorbol 12,13-dibutyrate ({3H}PDBu) and glycoprotein synthesis was observed following treatment of primary mouse epidermal cells with tunicamycin, a specific inhibitor of dolichol-mediated glycosylation . Following 18 h of treatment, the specific binding of {3H}PDBu was reduced to 33-56% of the control value . The total protein synthesis determined by leucine incorporation into acid-insoluble material was not altered by this antibiotic drug . These results suggest that the receptor for phorbol diesters is, or is functionally linked to, a glycoprotein on the cell surface.

J Gen Physiol, 1982 Sep, 80(3), 403 - 26
Monazomycin-induced single channels . I . Characterization of the elementary conductance events; Andersen OS et al.; Monazomycin (a positively charged, polyene-like antibiotic) induces voltage-dependent conductance changes in lipid bilayer membranes when added to one of the bathing solutions . These conductance changes have generally been attributed to the existence of channels spanning the membrane . In this article we characterize the behavior of the individual conductance events observed when adding small amounts of monazomycin to one side of a lipid bilayer . We find that there are several apparent channel types with one or sometimes two amplitudes predominating . We find further that these fairly similar amplitudes represent two different states of the same fundamental channel entity, presumed to be the monazomycin channel . The current-voltage characteristics of these channels are weakly hyperbolic functions of applied potential . The average lifetimes are essentially voltage independent (between 50 and 400 mV) . The average channel intervals, on the other hand, can be strongly voltage dependent, and we can show that the time-averaged conductance of a membrane is proportional to the average channel frequency.

J Cell Biol, 1982 Sep, 94(3), 586 - 91
Selection of tunicamycin-resistant Chinese hamster ovary cells with increased N-acetylglucosaminyltransferase activity; Criscuolo BA et al.; Chinese hamster ovary (CHO) cells resistant to the antibiotic tunicamycin (TM) have been isolated by a stepwise selection procedure with progressive increments of TM added to the medium . TM inhibits asparagine-linked glycoprotein biosynthesis by blocking the transfer of N-acetylglucosamine-1-phosphate from UDP-N-acetylglucosamine to the lipid carrier . The TM-resistant cells exhibited a 200-fold increase in their LD50 for TM and were morphologically distinct from the parental cells . The rate of asparagine-linked glycoprotein biosynthesis was the same for wild-type and TM-resistant cells . Membrane preparations from TM-resistant cells cultured for 16 d in the absence of TM had a 15-fold increase in the specific activity of the UDP-N-acetylglucosamine:dolichol phosphate N-acetylglucosamine-1-phosphate transferase as compared to membranes of wild-type cells . The products of the in vitro assay were N-acetylglucosaminylpyrophosphoryl-lipid and N,N'-diacetylchitobiosylpyrophosphoryl-lipid for membranes from both TM-resistant and wild-type cells . The transferase activity present in membrane preparations from wild-type of TM-resistant cells was inhibited by comparable levels of TM . The data presented are consistent with overproduction of enzyme as the mechanism of resistance in these variant CHO cells.

Vopr Pitan, 1982 Sep-Oct, (5), 63 - 6
{Effect of alpha-tocopherol on relations between RNA and ubiquinone biosynthesis in rat liver}; Donchenko GV et al.; The animals were kept on the low-protein diet deprived of vitamin E . Addition of the latter to the diet fed to a noticeable increase in the intensity of the biosynthesis of total and nuclear RNA of the rat liver . alpha-Tocopherol had a clearly marked stimulant effect on the synthesis of RNA and ubiquinone as shown by in vitro experiments under 30-minute preincubation of the liver from rats with E-hypovitaminosis . Meanwhile actinomycin D was found to inhibit these processes . Under preincubation with actinomycin D or concurrent introduction of the antibiotic with alpha-tocopherol the effect of the latter does no get realized . Unlike alpha-tocopherol, ionol and other synthetic antioxidants proved ineffective . It is assumed that the stimulant effect of vitamin E on the biosynthesis of ubiquinone in the liver of rats with E-hypovitaminosis is related to the increased intensity of the RNA synthesis and differs from the antioxidant one as regards the type . It is also assumed that the action of alpha-tocopherol on the RNA synthesis is effected at the transcriptional level.

J Bacteriol, 1982 Sep, 151(3), 1617 - 20
cdc9 ligase-defective mutants of Saccharomyces cerevisiae exhibit lowered resistance to lethal effects of bleomycin; Moore CW; Conditional ligase-deficient mutants of Saccharomyces cerevisiae were more sensitive than their parental (CDC9) strain to dose-dependent killing by bleomycin, even when mutant cells were pregrown and exposed to the antibiotic at permissive temperatures . Pretreatment incubation at the restrictive temperature (37 degrees C) under growing or nongrowing conditions enhanced bleomycin killing of both cdc9-1 and cdc9-9 mutants . This sensitization could be relieved by incubation at the permissive temperature before treatment.

Biochemistry, 1982 Aug 17, 21(17), 3927 - 32
Self-association of daunomycin; Chaires JB et al.; Daunomycin, a potent anthracycline antibiotic, self-associates in aqueous solution at concentrations greater than 10 microM . We report here visible absorbance, sedimentation equilibrium, and proton nuclear magnetic resonance (NMR) experiments that characterize this self-association . In contrast to earlier reports that the process is a simple dimerization, we find that an indefinite association model best fits our data, with an intrinsic association constant, Ki, equal to 1500 M-1 . From the temperature dependence of the observed NMR spectra, an enthalpy of approximately -8.0 kcal/mol is calculated . The NMR data show that the aromatic protons of the anthracycline portion of the drug are most affected by aggregation, probably due to stacking of the anthracycline rings . Knowledge of the applicable model for the self-association process, and the equilibrium constant that describes the process, enables us to assess quantitatively the possible effects of drug aggregation on the interpretation of drug-DNA binding data . For the ionic conditions most commonly used in such studies, the amount of aggregated daunomycin will be slight and may safely be ignored.

Jpn J Antibiot, 1982 Aug, 35(8), 2131 - 6
{Clinical use of acetylspiramycin for primary atypical pneumonia in the field of pediatrics}; Maruno H et al.; Thirty-one patients with primary atypical pneumonia (16 patients diagnosed as Mycoplasma pneumonia) who visited our Department of Pediatrics between March and December, 1981 were treated with 200 mg tablets of acetylspiramycin . Clinical effects were studied, and the results were as follows . 1 . Acetylspriramycin, in principle 30 mg/kg/day, was given to 31 patients with primary atypical pneumonia . The effective rate was 87.1% . (As for the patients with Mycoplasma pneumonia, the effective rate was 93.8%) . 2 . There was 1 ineffective case and it was judged as a case of other viral pneumonia by the results of clinical laboratory tests . 3 . The only side effect observed was eruption which occurred on the 6th day of administration in 1 case and disappeared after the change of administration . From the above results, acetylspiramycin is thought to be an effective antibiotic on primary atypical pneumonia.

Jpn J Antibiot, 1982 Aug, 35(8), 1993 - 7
{Clinical experience with cefoxitin used for the prevention of postoperative infections}; Kato F et al.; A total of 20 hospitalized patients underwent orthopedic surgery in the Tokyo Metropolitan Police Hospital during the period from December 1981 to March 1982 . These patients were treated with cefoxitin, mainly, for the prevention of postoperative infections . The following clinical findings were obtained . 1 . Out of the 20 patients, 14 were judged 'good' and 6 'fair' . 2 . No side effects were reported by the patients or were evident in the clinical data . 3 . These clinical results indicated that cefoxitin is a very effective antibiotic for the prevention of postoperative infections in orthopedic surgery.

Jpn J Antibiot, 1982 Aug, 35(8), 1987 - 92
{Treatment and prevention of infections with cefoxitin sodium in patients with biliary tract infections and obstructive jaundice}; Fuji T et al.; A total of 24 patients who was hospitalized in the Internal Medicine Wards of Yamaguchi University attached Hospital and the university's 3 related hospitals were administered with cefoxitin . The breakdown of the patients treated with cefoxitin was 7 with cholecystitis, 7 with choledochitis and the remaining 10 for the prevention of infections with obstructive jaundice . Daily doses of 2-6 g of cefoxitin were administered for 6-40 days by intermittent intravenous drip infusion in divided doses . Results: 1 . Of 14 patients with biliary tract infections, 10 (71.4%) responded favorably with cefoxitin . 2 . Of 10 patients with obstructive jaundice used for the prevention of infections, 8 (80%) responded favorably with cefoxitin . 3 . No untoward side effects were observed . 4 . Cefoxitin proved to be a safe and effective antibiotic in the treatment of biliary tract infections and for the prevention of infections in patients with obstructive jaundice.

Jpn J Antibiot, 1982 Aug, 35(8), 1907 - 10
{Clinical trials of netilmicin against respiratory tract infection}; Watanabe K et al.; Netilmicin, a new semisynthetic aminoglycoside antibiotic recently developed by Shering Co., was injected to 5 patients with respiratory tract infection (2 cases of diffuse panbronchiolitis, 2 cases of bronchiectasis and 1 case of bronchial asthma with infection) . A daily dose of netilmicin was 200 mg by intramuscular injection and duration of netilmicin therapy was for 7 to 14 days . Clinical response to netilmicin therapy of respiratory tract infection was good in 3 cases, fair in 1 case and poor in 1 case . No subjective and objective findings considered as the side effect was observed and laboratory examinations showed no abnormality . It may be concluded from the above clinical results that netilmicin may be effective for respiratory tract infections and further study may prove its efficacy.

J Antibiot (Tokyo), 1982 Aug, 35(8), 1013 - 9
Kitasatosporia, a new genus of the order Actinomycetales; Omura S et al.; The morphological, cultural, physiological and biochemical characteristics of a new actinomycete strain producing a new antibiotic, setamycin are described . The strain forms aerial mycelia . There is no fragmentation of vegetative mycelia . Since the cell wall type is a new one containing both LL- and meso-2,6-diaminopimelic acid, glycine and galactose, strain KM-6054 could not be classified in any previously named genera of the order Actinomycetales . Thus, it is considered to be a member of a new genus, for which the name Kitasatosporia is proposed . The type species (monotype) of this genus is K . setalba . The type strain of K . setalba is strain KM-6054 (ATCC 33774).

Pharmacol Biochem Behav, 1982 Aug, 17(2), 363 - 6
Schooling behavior of tadpoles: a potential indicator of ototoxicity; Lum AM et al.; Fish and tadpoles in schools use hair cells of their lateral line system to assess their position in relation to neighbors . This suggests that pharmaceutical agents that damage hair cells in the mammalian inner ear may also alter geometry in fish and tadpole schools . We used a computer-based image analysis system to examine the effect of the ototoxic aminoglycoside antibiotic, streptomycin, on school geometry for tadpoles of the African clawed frog Xenopus laevis . Tadpoles exposed to streptomycin in the surrounding water show a general tendency toward clumping, and an increase in the distance over which they orient parallel to neighbors, compared to controls . These behavioral responses appear in 18 min or less, and are evident in some tadpoles exposed to concentrations as low as 5 micrograms/ml . Results suggest that analysis of spatial relations in tadpole schools could serve as a method for rapidly detecting ototoxic potential of agents suspected of damaging hair cells.

J Comput Assist Tomogr, 1982 Aug, 6(4), 683 - 8
Diagnostic difficulties in computed tomography of brain abscesses; Holtas S et al.; In a series of 26 patients with the final diagnosis of brain abscess, 24 initially presented with ring lesions on computed tomography (CT) and two with homogeneous areas of increased attenuation after intravenous contrast medium administration . Twelve had a finding, reported to be characteristic, with a center of low attenuation encircled by a smooth, thin contrast enhancing ring surrounded by marked edema . In 10 patients, the true nature of the lesion was not evident from the first CT examination . An atypical appearance with a thick walled irregular ring or areas with homogeneous increased attenuation indicated malignant tumor . Rapidly progressing changes of the CT appearance and/or supplementary clinical data permitted us to reach the exact diagnosis in most of these . Repeat studies were also valuable in the follow-up during and after conservative (antibiotic) or surgical treatment.

Br J Surg, 1982 Aug, 69(8), 473 - 4
Intraoperative microscopy of bile--is it useful?
Gallagher P, Ostick G, Jones D, Schofield PF, Tweedle DE.
Direct microscopy of the bile was performed during cholecystectomy in 111 patients in an attempt to identify those with a high risk of wound infection . Bacteria were identified in 23 patients, 11 of 83 undergoing cholecystectomy alone and 12 of 28 undergoing exploration of the common bile duct (P less than 0.01) . These 23 patients were randomly allocated to an antibiotic group or a control group; there was one wound infection in the antibiotic group and two in the control group . A total of 14 patients developed wound sepsis . Infection was more likely if the common bile duct was explored (6 of 28) rather than cholecystectomy alone (8 of 83) . There was a poor correlation between microscopy and culture of the bile for bacteria and there was no increase in sepsis when bacteria were observed on microscopy . We were not able to identify a high risk group of patients by intraoperative microscopy of bile.

Br J Surg, 1982 Aug, 69(8), 459 - 60
Pre-incisional intraparietal injection of cephamandole: a new approach to wound infection prophylaxis; Armstrong CP et al.; Pre-incisional injection of cephamandole has been studied . Wound tissue levels of cephamandole have been found to be extremely high throughout the operation . Serum levels were compared to those obtained with parenterally administered antibiotic . The use of a pre-incisional injection of antibiotic therefore offers major theoretical advantages over the use of either conventional parenteral or topical antibiotics in the prevention of postoperative sepsis.

Am J Vet Res, 1982 Aug, 43(8), 1360 - 2
Bovine anaplasmosis: clinical, hematologic, and serologic manifestations in cows given a long-acting oxytetracycline formulation in the prepatent period; Lincoln SD et al.; The prophylactic efficacy of a long-acting oxytetracycline formulation was determined in 36 susceptible cows experimentally inoculated with Anaplasma marginale . Each of 10 cows in 3 treatment groups (T2, T3, T4) were given IM injections of 20 mg of oxytetracycline/kg of body weight once, twice, or three times during the prepatent period . The T2 group was treated once at 1 week after experimental inoculation, the T3 group was treated 2 times (at 1 and 2 weeks) after exposure, and the T4 group was treated 3 times (at 1, 2, and 3 weeks) after exposure . Six cows comprising group T1 served as nonmedicated controls . Treatment of cattle in the prepatent period with the long-acting oxytetracycline formulation produced significantly fewer clinical anaplasmosis cases . This reduction in frequency was proportional to the number of weekly treatments given . In cattle which developed clinical disease, only 1 IM injection of 20 mg of oxytetracycline/kg was necessary to induce recovery . The prepatent period in the treated cattle was extended approximately 30 days beyond the prepatent period of the control cattle after their final treatment . Humoral rapid card agglutinating and complement fixing antibodies regularly were present in the cows 10 days after they were inoculated; however, neither the presence of antibody nor that of the antibiotic was sufficient to prevent establishment of the carrier state in the principals.

J Thorac Cardiovasc Surg, 1982 Aug, 84(2), 291 - 6
Acute endocarditis: surgical treatment of aortic regurgitation and aortico--left ventricular discontinuity; Symbas PN et al.; The clinical course of five patients with acute endocarditis resulting in aortic regurgitation and aortico--left ventricular discontinuity was reviewed . All five patients were operated upon less than 6 weeks after the onset of the antibiotic therapy . Aortic valve replacement and repair of the left ventricular discontinuity were done successfully in all five patients . The repair was accomplished in two patients primarily, with interrupted horizontal pledget-supported sutures placed through the left ventricular and aortic walls and through the ring of a valve prosthesis . In the remaining three patients, the repair was performed with the interposition of a Dacron patch between the left ventricle and the aorta, and the valve prosthesis was then sutured to the graft and to the remaining native aortic anulus . The latter technique has many attractive features for the repair of left ventricular discontinuity when there exists a large gap between the aorta and left ventricle.

Br J Surg, 1982 Aug, 69(8), 461 - 2
Preoperative intraparietal (intra-incisional) cefoxitin in abdominal surgery; Taylor TV et al.; The effect of preoperative intraparietal (intra-incisional) injection of cefoxitin along the site of the intended incision on the incidence of wound infection has been investigated by a randomized prospective study of 181 consecutive patients undergoing abdominal surgery . A significant reduction in wound infection was evident in the cefoxitin-treated group (4.4 per cent) when compared with controls (16.7 per cent) (chi 2 = 6; P = 0.02) . Administration of antibiotic by this route did not delay wound healing or produce any undesirable sequelae.

Ann Intern Med, 1982 Aug, 97(2), 216 - 9
Therapy of cervical chlamydial infection; Brunham RC et al.; The treatment of cervical Chlamydia trachomatis infection in nonpregnant women was evaluated in a double-blind randomized study . Objective criteria were used to assess the response of cervicitis to therapy . Fifty patients were treated with tetracycline hydrochloride, 500 mg orally four times daily, and 50 patients were treated with rosaramicin, 250 mg orally four times daily, both for 7 days . Both agents were highly effective in eradicating C trachomatis . Both produced significant improvement in objective signs of cervicitis: eliminating mucopurulent endocervical discharge and edema of ectopy, and decreasing the clinical severity score of cervicitis . This trial shows that the 1-week course of tetracycline hydrochloride currently recommended for treatment of chlamydial urethritis in men is also highly effective for the treatment of chlamydial cervical infection in women . Rosaramicin, a macrolide antibiotic, was equally effective but produced a higher rate of gastrointestinal side effects.

J Biochem (Tokyo), 1982 Aug, 92(2), 585 - 90
Enzyme immunoassay of blasticidin S with high sensitivity: a new and convenient method for preparation of immunogenic (hapten-protein) conjugates; Kitagawa T et al.; An antibody against blasticidin S (BLS), an antibiotic effective for blast disease of rice, has been produced in rabbits immunized with a blasticidin S-protein conjugate prepared by a novel and convenient procedure devised to couple BLS to bovine serum albumin (BSA) after sodium borohydride reduction of its disulfide bonds, using N-(m-maleimidobenzoyloxy)succinimide (MBS) as a cross-linker . BLS-MBS-BSA conjugate contained about 16 BLS per BSA molecule . Enzyme labeling of BLS with beta-D-galactosidase was performed by utilizing another cross-linker, N-(gamma-maleimidobutyryloxy)succinimide by means of a convenient labeling method which we introduced last year . A double antibody enzyme immunoassay of BLS which could determine as little as 100 pg per tube of BLS was developed using labeled BLS and anti-BLS antiserum . Various commonly used drugs were found to have little reactivity in this immunoassay, indicating that the anti-BLS produced is highly specific . The titer of the anti-BLS was excellent and 10,000,000-fold diluted solution could bind with the enzyme labeled BLS.

Can J Ophthalmol, 1982 Aug, 17(4), 153 - 6
Treatment of blepharitis and blepharoconjunctivitis: comparison of gentamicin-betamethasone, gentamicin alone and placebo; Jackson WB et al.; At two university centres 46 patients presenting with symptomatic infective blepharitis or blepharoconjunctivitis participated in a double-blind study of a new antibiotic-steroid ointment containing gentamicin and betamethasone . There was no significant difference in response to 2 weeks of therapy between the patients treated with this ointment and those treated with either an ointment containing gentamicin alone or a placebo ointment . There was also no significant correlation between the clinical response and the results of the bacterial cultures of swabs obtained at the beginning and the end of the study . However, the patients treated with the placebo had a much higher rate of recurrence of their symptoms over a 6-week follow-up period . The patients who before treatment had associated rosacea, dry eyes and a long duration of symptoms showed a poor response to therapy.

Antibiotiki, 1982 Aug, 27(8), 623 - 6
{57Co-bleomycetin pharmacokinetics in the body of mice with LIO-1 lymphosarcoma}; Petriev VM et al.; Pharmacokinetics of 57Co-bleomycetin was studied on mice with lymphosarcoma LIO-1 . It was found that at early periods of intravenous administration of the labeled antibiotic, i.e . within the period from 5 minutes to 1 hour its higher levels are detected in the liver, kidneys, blood serum, lungs, intestine and tumor . At later periods the drug levels in the organs and tissues gradually decrease and by the 72nd hour the concentration of 57Co-bleomycetin in the blood serum appears to be 30 times lower as that after 5 minutes . In the muscles and tumor its concentrations by that period are 15 and 2 times lower respectively . Radiometry of the animals showed that within the first 24 hours more than 85 per cent of 57Co-bleomycetin was excreted from the mice.

Biochim Biophys Acta, 1982 Jul 28, 689(2), 219 - 29
Lipid monolayer expansion by calcium-chlorotetracycline at the air/water interface and, as inferred from cell shape changes, in the human erythrocyte membrane; Riquelme G et al.; Chemically induced shape changes of the human erythrocyte may result from cell membrane bending by surface tension changes at the lipid bilayer (Evans . E.A . (1974( Biophys . J . 14, 923-931) implicating differential expansion of the monolayers coupled to form the red cell membrane (Sheetz, M.P . and Singer, S.J . (1974) Proc . Natl . Acad . Sci . U.S.A . 71, 4457-4461) . Interacting with calcium, the antibiotic chlorotetracycline (CTC) transforms crenated cells (echinocytes) into cup-shaped ones (stomatocytes), presumably expanding thereby the red cell membrane inner leaflet relative to the outer one (Behn, C., Lubbemeier, A . and Weskamp, P . (1977) Pflugers Arch . 372, 259-268) . Whether the Ca-CTC interaction with lipid monolayers may in fact expand the latter, has now been examined by surface tension measurements at the air/water interface . CTC and lipids appeared to compete for the available sites at the air/water interface, contributing additively to its surface pressure . Ca increased both the adsorption rate of the antibiotic to the interface and the CTC-induced surface pressure increment . The latter was not influenced by the subphase pH and ionic strength, or by the type of phospholipid polar head . Correspondingly, CTC-induced cell shape changes should be determined by the pCa values facing either monolayer of the erythrocyte membrane . Both stomatocytes and echinocytes could indeed by obtained with 0.5 mmol . 1(-1) CTC, the cell shape depending on whether the external medium was adjusted respectively to pCa 9 or to pCa 3 . Fluorescence microscopy revealed the Ca-CTC complex to be mostly restricted to the cell in stomatocytes and to the external medium in echinocytes . The possibility of inducing alternative cell shapes by varying the transmembrane Ca-CTC distribution, and the demonstration of a Ca-dependent expansion of even relatively compressed lipid monolayers by CTC, together suggest that the Ca-CTC complex may also differentially expand either leaflet of the red cell membrane.

Med J Aust, 1982 Jul 24, 2(2), 86 - 9
Intravenous cannulas . Survey of their use in patients undergoing elective surgery; Holland RB et al.; A study of the complications associated with use of intravenous cannulas was conducted in 254 patients undergoing elective surgery at Westmead Centre . Four brands of cannula were studied . Surflo, Jelco, Dwellcath and Abbocath . It was found that the Surflo cannula was the most frequently used at Westmead Centre, that the dorsum of the hand was the site with the least number of complications, and that gauge of cannula had no influence on the rate of complications . Complications were more likely with blood transfusion or addition of potassium or antibiotic agents to the infusion, and the increasing duration of infusion . Abbocath cannulas had fewer complications associated with their use than the other cannulas studied.

Biochemistry, 1982 Jul 20, 21(15), 3711 - 21
Structural basis for the deoxyribonucleic acid affinity of bleomycins; Kross J et al.; The role of the bithiazole moiety of bleomycin in the interaction of the antibiotic with DNA has been studied by the use of synthetic bithiazole derivatives . The DNA affinity of individual C-terminal (bithiazole) analogues of bleomycin was measured in terms of the ability of these species to block the binding of bleomycin to DNA, as judged by diminution of the DNA degradation that attends bleomycin binding . DNA degradation was monitored both by release of {3H}thymine from radiolabeled PM-2 DNA and by alteration of bleomycin-treated DNA oligomers of defined sequence derived from Escherichia coli plasmid pLJ3 . It was found that the affinity of the bithiazole derivatives for DNA depended on the presence of the bithiazole moiety itself but more importantly on the number and spacing of positively charged groups; 2'-(2-aminoethyl)-2,4'-bithiazole-4-{3-{(4-aminobutyl) amino}propyl}carboxamide (14), having three positively charged groups at neutral pH, was a reasonably effective inhibitor of DNA degradation by bleomycin . Consistent with the importance of the spacing of the positively charged groups, tetrapeptide S (12) was found to be significantly less inhibitory toward DNA degradation by bleomycin than tripeptide S, in spite of their equal number of positively charged groups and the greater structural similarity of the former to bleomycin A2 . Bleomycin is known to cleave DNA perferentially at certain sequences . It was shown that the inhibitors employed in this study diminished DNA cleavage proportionately at each cleavage site; no alteration was observed in the specificity of cleavage . A number of the bithiazole analogues employed as inhibitors of bleomycin-mediated DNA degradation were also utilized in fluorescence quenching experiments with calf thymus DNA . Consistent with the belief that these species inhibit bleomycin degradation by competitive binding to the DNA substrate, the best inhibitors exhibited the greatest fluorescence quenching upon admixture of DNA.

Gan To Kagaku Ryoho, 1982 Jul, 9(6), 1097 - 101
{Antitumor activity of macromomycin}; Kato T et al.; An antitumor activity of macromomycin, a polypeptide antitumor antibiotic, was tested in vitro and in vivo . The results obtained were as follows: 1) The cytostatic effect on L1210 cells in culture was identical to that of neocarzinostatin . 2) The effect of MCR on the survival of L1210 or P388 leukemia was as same level as NCS . 3) Effects of MCR were independent from the treatment schedules . 4) MCR was inactive on the survival of Lewis lung carcinoma.

J Submicrosc Cytol, 1982 Jul, 14(3), 441 - 52
Comparison of the response of myocardial muscle and capillary endothelial nuclear membranes to the cholesterol probe filipin; Severs NJ; The polyene antibiotic filipin was used as a probe for cholesterol in the nuclear membranes of cardiac muscle and capillary endothelial cells . Samples of perfusion-fixed rabbit and rat myocardium were exposed to filipin in glutaraldehyde fixative, prior to examination by standard freeze-fracture techniques . Quantitative analysis of the responses of the inner and the outer nuclear membranes of the two cell types was carried out by measuring the numerical density of filipin-induced lesions in each . Cardiac muscle cell outer nuclear membranes displayed few or no lesions (less than 0.1 micron-2), and their inner nuclear membranes were completely resistant to the treatment . By contrast, a marked response to filipin was found in the endothelial nuclear envelope, the outer membrane showing an average of 250 lesions micron-2, and the inner membrane 63 lesions micron-2 . These results are interpreted as a direct reflection of differences in cholesterol content between the outer and inner nuclear membranes of the two cell types . The significance of the apparent differences in cholesterol content demonstrated between the nuclear envelopes of different cell types is discussed with reference to biochemical data, plasma membrane cholesterol content, nuclear membrane function and the supply of exogenous cholesterol.

Ann Acad Med Singapore, 1982 Jul, 11(3), 322 - 35
Child health in Singapore--past, present and future; Wong HB; PIP: The state of child health in Singapore from 1914 to the present is discussed . In 1914 there were 225 reported cases of tetanus neonatorum out of 7420 births and 340 deaths from gastroenteritis with an infant mortality rate (IMR) of 292.9/1000 live births . In 1936 the IMR was 167.74 and in 1962 it was still high at 31.2 . Causes of death included tetanus neonatorum, gastroenteritis, tuberculosis, and poliomyelitis . Diphtheria immunization had lowered the rate of mortality from this disease . The 1st priority in improving infant health after 1962 was lowering the IMR, especially by treating the newborn . The 2nd priority was infections . Oral Sabin was introduced against polio and programs for tetanus, whooping cough, and measles vaccinations were begun as well; compulsory diphtheria innoculation began in 1963 . Malnutrition was identified as a cause in high childhood morbidity and mortality, relating to a decrease in breastfeeding to only 29% with only about 4% continuing after 3 months; this also caused diarrhea and gastroenteritis . A Breast Feeding Mothers Group was established to help mothers and to support a breast milk bank . In addition the birthrate was very high, 2.8% with very young and elderly mothers giving birth in large numbers and constituting poor obstetric risks . In 1966 the government established a national family planning program . This program, together with nutrition education, improved housing and promotion of breastfeeding has raised the nutrition level . By 1976 the IMR had fallen to 11.8 and the neonatal mortality rate (NMR) was 8.4, both of which were lower than rates in the US, UK, Australia, and New Zealand . In 1981 the IMR fell to 10.8 and the NMR to 7.7 . Although deaths from infections and diseases have dropped, those from congenital anomalies and malignancies such as leukemia have not changed . Health education has had an effect on lowering mortality rates from accidents . Rates of death from dengue hemorrhagic fever have been lowered but not abolished by mosquito surveillance, as is the case with other viral infections such as measles . With bacterial infections the latest problem is the existence of antibiotic-resistant strains . Further efforts must emphasize health rather than the reduction of mortality and mental and emotional morbidity must receive more attention as well .

Somatic Cell Genet, 1982 Jul, 8(4), 521 - 32
Isolation and characterization of puromycin-resistant clones from cultured mosquito cells; Fallon AM et al.; We have isolated from an established Aedes albopictus (mosquito) cell line clones which are resistant to the antibiotic puromycin . On the basis of growth and plating efficiency, clones Pur-8026 and Pur-8612 were five- and seven-fold more resistant, respectively, to puromycin than wild-type cells . In vitro protein synthesis was resistant to puromycin only in extracts prepared from Pur-8612 cells . Measurements of puromycin transport, cross-resistance to colchicine, and sensitivity to Tween-80 indicating that resistance in Pur-8026 cells was due to membrane alteration(s) affecting permeability to puromycin . This is the first description of puromycin resistant in insect cells and also the first report of puromycin resistance in an animal cell variant associated with an alteration at the level of protein synthesis.

Int J Dermatol . 1982 Jul-Aug;21(6):349.
Keratoacanthoma as a complication of arterial puncture for blood gases; Shellito JE et al.; In July 1979, a 72-year-old white woman presented to the Bernalillo County Medical Center Emergency Department with complaints of shortness of breath and wheezing . She had been asthmatic since childhood . Current management included bronchodilator therapy and continuous low flow oxygen . An apparently curative left radical nephrectomy had been performed in 1978 for renal cell carcinoma . Her evaluation in the emergency room included multiple attempts at right radial artery puncture for blood gases . The arterial blood gases were obtained only after repeated efforts by several individuals . The patient was discharged from the emergency room after receiving subcutaneous terbutaline and intravenous aminophylline . Approximately one week later, she noticed a swelling on her right wrist at the site of the punctures . Over the ensuing three weeks, the lesion doubled in size and became painful . In chest clinic, one month after emergency room visit, we found a 1 cm by 1 cm raised erythematous tender nodule on the right wrist overlying the radial artery pulse . We did not hear a bruit, the lesion did not feel fluctuant, and attempts to aspirate fluid were unsuccessful . Because we thought the lesion represented local infection, we began oral antibiotic therapy . The lesion was unchanged after 1 1/2 weeks of therapy and was excised . Pathologic examination showed a well-defined cutaneous nodule with histology diagnostic of a keratocanthoma . The patient developed a recurrence of the tumor at the excision site a few weeks later and required a wide excision, also under local anesthesia . She has since remained clinically free of recurrent tumor.

Eur J Biochem, 1982 Jul, 125(3), 585 - 91
Effect of tunicamycin on thyroglobulin secretion; Bjorkman U et al.; Secretion of thyroglobulin was studied by incubating pig thyroid follicles, isolated by collagenase digestion and opened up by trypsinization . When followed over periods of 4 h, the secretion of {14C}leucine-labeled thyroglobulin into the medium was reduced by 60-95% in the presence of 1 microgram/ml and 5 micrograms/ml of tunicamycin . These concentrations of the antibiotic reduced incorporation of {3H}mannose into the follicle proteins by 70-80% but did not significantly influence the incorporation of {14C}leucine . Rat thyroid lobes were labeled with {3H}leucine for 20 min and chase-incubated for 0-4 h . In electron microscopic autoradiographs obtained immediately after labeling, the label was restricted to the follicle cells and concentrated over the endoplasmic reticulum both in controls and in specimens exposed to tunicamycin (5 micrograms/ml) . After 4 h chase most radioactivity was located in the follicle lumen in controls whereas in tunicamycin-exposed lobes almost all labeled material was retained in the follicle cells . It is concluded that tunicamycin suppresses thyroglobulin secretion and that this is not due to inhibited protein synthesis.

J Clin Microbiol, 1982 Jul, 16(1), 96 - 8
Comparison of direct and standard microtiter broth dilution susceptibility testing of blood culture isolates; Kiehn TE et al.; Turbid broth (0.5 ml) from blood culture bottles was inoculated into 0.5 ml of brain heart infusion broth, incubated for 3 to 6 h, diluted 1:500 in distilled water, and then inoculated directly into microtiter broth dilution susceptibility trays to test for minimal inhibitory concentrations . The results were compared to the standard tests performed 24 h later on colonies from subculture plates . The minimal inhibitory concentrations measured by these two methods were compared in 1,875 organism-antibiotic tests . The two minimal inhibitory concentrations were identical in 86.0% and within one twofold dilution in 98.0% of the tests . An organism was judged to be susceptible by one method and resistant by the other in 13 tests (0.7%) . These 13 discrepancies were distributed among several organism-antibiotic combinations; no more than two were seen for any one combination . Highly accurate susceptibility testing can be achieved by using direct inoculation of turbid blood culture broths.

Hepatology, 1982 Jul-Aug, 2(4), 399 - 407
Spontaneous bacterial peritonitis; Hoefs JC et al.; Forty-three patients with spontaneous bacterial peritonitis (SBP) between 1973 and 1978 were identified . Criteria for SBP included a positive ascites culture and polymorphonuclear cell concentration greater than 250 cells per mm3 . Chronic liver disease was documented by varices in 91%, severe histologic fibrosis or cirrhosis in 94%, splenomegaly in 91%, and past hospitalization for liver disease in 57% of the patients . SBP was detected within 7 days of admission in 17 patients (40%) and within 35 days in 38 patients . Single organisms were isolated from 38 patients and multiple organisms from 5 patients . Twenty-six of 43 patients survived the episode of SBP, but only 13 survived the hospitalization . Analysis of the survival curve from the onset of SBP revealed a rapid death rate and a slow death rate set of patients . Rapid death (less than or equal to 7 days from SBP onset) correlated with a lack of prior hospitalization for liver disease (p less than 0.001), hepatomegaly (p less than 0.001), increased serum bilirubin (p less than 0.005), serum creatinine (p less than 0.05), and peripheral white blood cell concentrations (p less than 0.05) . Survival during hospitalization was associated with prior hospitalization with liver disease (p less than 0.001) and chills during the episode of SBP (p less than 0.001) . The 43 patients were divided into Group 1 patients on the basis of a serum bilirubin greater than 8 mg% and/or serum creatinine greater than 2.1 mg%; Group 2 patients had lower values . Survival was greater in Group 2 patients with advanced, relatively quiescent liver disease compared to Group 1 patients for both the episode of SBP (91 vs . 29%; p less than 0.001) and for hospitalization (50 vs . 9%; p less than 0.05) . Death in Group 2 patients was related to inadequate antibiotic therapy (p less than 0.05), nonhepatic factors, and new onset of renal failure . Although SBP in the setting of severe acute liver injury has a dismal prognosis, SBP with minimal acute liver injury has a relatively good prognosis for hospital survival even with advanced chronic liver disease . Long-term survival is also possible since 4 of 9 patients with prolonged follow-up have survived 3 years.

Clin Orthop, 1982 Jul, (167), 191 - 6
Nonunion of the tibia treated with Küntscher intramedullary nailing; Clancey GJ et al.; Nonunion of the tibia was treated by Kuntscher intramedullary nailing un 48 patients . Thirty patients were treated with a completely closed intramedullary nailing and 18 required an open tibial osteotomy to realign the fracture . Bone grafting was not performed . The average time elapsed from injury to surgery was 15 months and the average healing time, as determined roentgenographically, was nine months following surgery . Three postoperative infections cleared with debridement and antibiotic therapy and subsequently united . There were two failures with persistent nonunion . Closed intramedullary nailing is an effective method of managing nonunion of the tibia in properly selected cases.

Clin Orthop, 1982 Jul, (167), 123 - 30
Primary endoprosthetic replacement for acute femoral neck fractures . A review of 150 cases; Johnston CE et al.; A review of 150 consecutive endoprosthetic replacements for acute displaced femoral neck fractures was undertaken to investigate the following serious criticisms of the method . The first is excessive hospital mortality and morbidity, especially in comparison to internal fixation procedures retaining the femoral head . The second is pain, derived from the "unphysiologic" nature of placing a metal prosthesis against otherwise normal acetabular cartilage . In the first instance the procedure is condemned as too major an operative procedure, poorly tolerated by elderly patients . In the second, it is a poor procedure if it requires revision in a patient incapable of withstanding more than one operation . A detailed follow-up shows that the in-hospital mortality in patients averaging 79.8 years of age, was 4%, lower than published mortality for either hemiarthroplasty or internal fixation . Close postoperative monitoring, antibiotic and antiembolic prophylaxis (2.0% infection, 6% embolic complications), and rapid mobilization contributed significantly to the increased survival . Painful endoprostheses, the most frequent complication, occurred in 16.7% of the 125 patients available for follow up at an average of 21 months . The causes of pain were considered technical problems judging prosthetic neck length, head size, sinking and loosening . Dissolution of the medial femoral neck was associated with a narrow stem prosthesis in five of six of these failures . The above statistics suggest that primary endoprosthetic replacement for displaced femoral neck fractures carries with it neither the excessive mortality and morbidity nor the pain induced potential for early reoperations that have been suggested by the recent literature.

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