Antibiotics

Arch Immunol Ther Exp (Warsz), 1985, 33(6), 851 - 6
Characteristics of Mycoplasma strains isolated from stallion semen; Zgorniak-Nowosielska I et al.; Eleven mycoplasma strains were isolated from the semen of 24 stallions . Eight of these strains were identified as Mycoplasma equigenitalium . Three strains which hydrolized arginine could not be identified . The growth inhibition test with immune sera against M . arginini and M . equirhinis was negative . Antibiotic sensitivity test showed that all strains were sensitive to four antibiotic of tetracycline group (oxytetracyclin, minocycline, transcycline and vibramycin) . Lincomycin and gentamycin appeared to be the most active against all the strains . Comparative analysis of routine semen examination did not reveal any difference between ejaculates infected with mycoplasma and free of these organisms . However, the levels of certain biochemical components of the semen plasma (glycerylphosphorylcholine, ergothioneine, fructose and of the semen plasma (glycerylphosphorylcholine, ergothioneine, fructose and total protein) from mycoplasma-positive ejaculates were significantly lower than in the semen plasma from mycoplasma free ejaculates.

Nucleic Acids Symp Ser, 1985, (16), 141 - 4
Protected 2'-deoxyaristeromycin on polymer support: a substitute for the acid labile 2'-deoxyadenosine moiety at the 3'-terminus of oligodeoxynucleotides; Miyashita O et al.; A modified nucleoside antibiotic on polymer support was employed in the solid-phase synthesis of two oligodeoxynucleotides to substitute acid labile 2'-deoxyadenosine(A) at the 3'-terminus of oligomers with acid resistant 2'-deoxyaristeromycin(Ar) . The duplex of the decamer having sticky ends was inserted successfully into the Eco R1 site of pBR322 . E . coli DH 1 was transformed with the Ar-containing plasmid . Inspection of the cloned plasmid pBR2552 by restriction endonucleases revealed that no deletion and insertion occurred near the inserted sequence . This result indicates that Ar can behave as A in DNA replication of the host cells . Therefore, Ar can be used as a substitute for 3'-terminal A in the solid-phase oligonucleotide synthesis.

Mol Gen Genet, 1985, 199(3), 401 - 5
Effects of polymyxin B sulfate and polymyxin B nonapeptide on growth and permeability of the yeast Saccharomyces cerevisiae; Boguslawski G; Polymyxin B, a toxic, membrane-affecting antibiotic, can be rendered harmless to yeast cells by enzymatic removal of its fatty acyl moiety . The remaining cyclic peptide portion, polymyxin B nonapeptide, has no significant effect on growth and viability but it drastically reduces mating efficiency . In addition, the cyclic peptide enhances sensitivity of cells to several drugs, presumably by increasing membrane permeability . Mutants resistant to polymyxin B are simultaneously less responsive to the combination of the nonapeptide and the drugs . This indicates that the peptide portion of polymyxin B is the moiety responsible for the permeability changes . The resistance is inherited as a simple recessive trait . The mutation has been mapped to chromosome XV of Saccharomyces cerevisiae.

J Basic Microbiol, 1985, 25(5), 325 - 33
Influence of inorganic phosphate on the lipid synthesis of a phosphate-deregulated mutant of Streptomyces noursei; Hanel F et al.; Phosphate-dependent changes of the mycelial lipid composition were studied in the streptothricin-producing parental strain Streptomyces noursei JA 3890 b/2 and its mutant RG 2 . In contrast to its ancestor, the mutant was capable of producing the antibiotic nourseothricin even when large quantities of inorganic phosphate were present in the medium . The apparent insensitivity of the secondary metabolism to phosphate inhibition corresponds to a decreased level of phospholipids in the presence of excessive inorganic phosphate and, during phosphate limitation, to a much higher production of the alkaline phosphatases . A model is discussed which proposed the control by a common genetic element of both the phospholipid and antibiotic production.

J Basic Microbiol, 1985, 25(3), 175 - 86
Influence of nourseothricin on growth and secondary metabolism of Streptomyces noursei JA 3890b; Roder B et al.; The nourseothricin-producing S . noursei strain JA 3890b possessed a high degree of resistance to its own antibiotic when grown in submerged cultures started from mycelium samples as inocula . In contrast, both the outgrowth of spores and the development of surface colonies from mycelium samples were severely inhibited in the presence of relatively low concentrations of nourseothricin, suggesting that the producer organism is susceptible to the autotoxic metabolite in particular stages of its development . Nourseothricin production by submerged cultures has been found to be independent of negative feedback regulation by the antibiotic.

Pharmacol Res Commun, 1985 Jan, 17(1), 33 - 47
Captopril inhibits sodium and water transport in the toad skin, a model of the distal nephron; Orce GG et al.; Captopril (SQ 14225), an orally active angiotensin I-converting enzyme inhibitor (CEI), increases natriuresis and diuresis in man and experimental animals in vivo, as well as in the isolated perfused rat kidney, raising the possibility of a direct renal action of the drug . We tested this hypothesis by studying its effects in the isolated toad skin, a model of the distal nephron devoid of vascular and nervous influences . When added to the dermal bath, captopril caused a reversible, concentration-related decrease in short-circuit current (SCC), a measure of active transepithelial Na transport . Keeping the toads in 0.1 M NaCl for 4 or more days increased sensitivity to the drug, which then inhibited SCC maximally (49 +/- 12% at 3.4 X 10(-3) M, P less than 0.01, n = 10), suggesting its effect might be modulated by endogenous mineralocorticoid activity . Captopril also inhibited the increase in SCC and in osmotic water permeability caused by neurohypophyseal peptides (NHP) . The increases in SCC by non-peptidic agents (nystatin, a polyene antibiotic, or norepinephrine, an adrenergic agonist) were not altered, ruling out a generalized toxic effect, or any significant inhibition of the Na pump by captopril . The apparently specific effect of the drug on the permeability responses to NHP seems to be exerted proximally to the apical border, since the response of the latter to other agents was preserved . The present data suggest SH groups may be involved, since other CEI lacking such groups (teprotide and MK-422) do not produce such effects . These observations support the notion that a direct tubular effect may be involved in the increased diuresis and natriuresis observed after administration of captopril.

Mol Biol (Mosk), 1985 Jan-Feb, 19(1), 177 - 95
{Specific protection of DNA by distamycin A, netropsin and bis-netropsins against the action of DNAse I}; Skamrov AV et al.; Interaction of netropsin, distamycin A and a number of bis-netropsins with DNA fragments of definite nucleotide sequence was studied by footprinting technique . The nuclease protection experiments were made at fixed DNA concentration and varying ligand concentrations . The affinity of ligand for a DNA site was estimated from measurements of ligand concentration that causes 50% protection of the DNA site . Distribution pattern of the protected and unprotected regions along the DNA fragment was compared with the theoretically expected arrangement of the ligand along the same DNA . The comparison led us to the following conclusions: 1 . Footprinting experiments show that at high levels of binding the arrangement of netropsin molecules along the DNA corresponds closely to the distribution pattern expected from theoretical calculations based on the known geometry of netropsin--DNA complex . However, the observed differences in the affinity of netropsin for various DNA sequences is markedly greater than that expected from theoretical calculations . 2 . Netropsin exhibits a greater selectivity of binding than that expected for a ligand with three specific reaction centers associated with the antibiotic amide groups . It binds preferentially to DNA regions containing four or more successive AT pairs . Among 13 putative binding sites for netropsin with four or more successive AT pairs there are 11 strong binding sites and two weaker sites which are occupied at 2 D/P less than or equal to 1/9 and 2 D/P = 1/4, respectively . 3 . The extent of specificity manifested by distamycin A is comparable to that shown by netropsin although the molecule of distamycin A contains four rather than three amide groups . At high levels of binding distamycin A occupies the same binding sites on DNA as netropsin does . 4 . The binding specificity of bis-netropsins is greater than that of netropsin . Bis-netropsins can bind to DNA in such a way that the two netropsin-like fragments are implicated in specific interaction with DNA base pairs . However, the apparent affinity of bis-netropsins estimated from footprinting experiments is comparable with that of netropsin for the same DNA region . 5 . At high levels of binding bis-netropsins and distamycin A (but not netropsin) can occupy any potential site on DNA irrespectively of the DNA sequence . 6 . Complex formation with netropsin increases sensitivity to DNase I at certain DNA sites along with the protection effect observed at neighboring sites.

Proc Natl Acad Sci U S A, 1985 Jan, 82(1), 158 - 62
Transfer of genes into hematopoietic cells using recombinant DNA viruses; Karlsson S et al.; The ability of recombinant DNA viruses to transfer genes into hematopoietic cells has been explored . A recombinant simian virus 40 (SV40) in which the early region had been replaced with the chloramphenicol acetyltransferase (CAT) gene driven by the promoter from Rous sarcoma virus (RSV), was constructed . This virus transferred the CAT gene more efficiently into mouse and human bone marrow cells and into the K562, MEL, and WEHI hematopoietic tissue culture cell lines, than the classical calcium phosphate DNA transfer procedure, as shown by assay for CAT activity 48 hr after infection . Recombinant SV40 virions were also shown to be capable of stably transforming Chinese hamster ovary cells by use of an early region recombinant containing the methotrexate-resistant dihydrofolate reductase (DHFR) gene driven by the RSV promoter . The entire DHFR transcriptional unit could be detected in the genome of transformed cells that were also shown to be resistant to methotrexate . A recombinant adenovirus stock containing the neomycin-resistance gene driven by the SV40 early promoter was used to infect the K562 and MEL hematopoietic cell lines to resistance to the antibiotic G418 . Transformation frequency was 10- to 100-fold higher than that obtained with calcium phosphate-precipitated DNA . Most or all of the recombinant adenovirus genome was integrated as 1-3 copies in the transformed cells . These studies show the feasibility of using DNA viruses for introduction of new genetic material into hematopoietic cells.

Vutr Boles, 1985, 24(6), 78 - 84
{Pyogenic liver abscesses--diagnostic and surgical problems}; Merdzhanov A et al.; The authors discuss the clinical-diagnostic and surgical problems in the treatment of the pyogenic hepatic abscesses . Eight patients, undergone the operation during the second period after 1971, were out of 18 patients operated (1951--1983) were analyzed in details . An inexplicable predomination of males and affection of all age groups is reported . The abscesses are cryptogenic in 2 of the patients, after operation of the hepaticbiliary system--in 2, after gastric operation--in 3, after abdominal trauma--in 1 . The possible way of penetration of the infection is discussed . In was established that it parallel with the characteristic clinical picture and biochemical deviations, typical for the septic process, a definite diagnosis is made via echography and computer tomography, supported by scintigraphy, angiography, punching of the abscess, inspection graphy of the hepatic region . The treatment is difficult and complex: Antibiotic, generally tonizising and surgical . The choice of the operative approach denends on the localization, number of the abscesses and character (pyogenic, amebic, etc) . The therapeutic tasks are discussed as well as the operation methods applied, punch-aspiration including . The risk of complications and lethality remain high, three patients were discharged healthy, with improvement--2, deceased--3 (sepsis, stress-ulcer, pulmonary embolism).

Acta Biomed Ateneo Parmense, 1985, 56(1), 23 - 6
{Use of oral bacteria therapy in childhood during acute enteritis and functional chronic diarrhea . Clinical experience}; Gregori G et al.; There are some theoretical reasons to give an oral bacterial therapy when intestinal ecosystem changes its composition . The authors would verify the clinical effectiveness or oral bacterial therapy during acute and functional chronic diarrhea: even if the course of the illness doesn't become shorter, oral bacterial therapy moreover may be useful in reducing the risk of having casual carries of pathogenic agents and may restore an intestinal ecosystem previously modified by antibiotic therapy.

Microbios, 1985, 44(177), 51 - 66
Mechanism of stimulation of Ca2+ uptake by miconazole and ethidium bromide in yeasts: role of vacuoles in Ca2+ detoxification; Eilam Y et al.; The antifungal antibiotic miconazole and the cationic dye ethidium bromide, both caused K+ efflux, membrane depolarization and intracellular acidification in the yeast Saccharomyces cerevisiae . Whereas miconazole inhibited the activity of the plasma membrane H+-ATPase, no such inhibition was observed using ethidium bromide at concentrations up to 600 microM . Low concentrations of both drugs caused marked stimulation of the energy dependent Ca2+ uptake . The extra Ca2+ taken up in the presence of the drugs was localized within the vacuoles, whereas K+ was lost mainly from the cytosolic pool . The ions Zn2+ and La3+ inhibited the effect of both drugs on the stimulation of Ca2+ uptake . The results indicated that both drugs caused an increase in the permeability of cell membranes to ions, leading to an increase in the influx of Ca2+ into the cytosol along its electrochemical gradient . Consequently, the concentration of Ca2+ within the cytosol increased and in turn led to the enhancement of Ca2+ uptake by the energy dependent vacuolar Ca2+ system, which functioned as a Ca2+ detoxification system.

Acta Med Hung, 1985, 42(3-4), 163 - 74
Therapeutical experiments in ulcerative colitis and Crohn's disease; Nagy G et al.; In the period 1963-82 among the patients with aspecific inflammatory bowel disease, the incidence of ulcerative colitis was 3.1 per 100 000 per year, while the frequency of Crohn's disease has doubled during the observation period and now its incidence is 0.58 per 100 000 per year . During the past 20 years, 404 patients with ulcerative colitis were treated . The average follow-up of the patients lasted for 6.6 years . During this period, 40% of the patients could be kept in balance permanently with salicylazosulfapyridine (SASP) monotherapy . A further 34% reacted to SASP plus steroid . The rate of regression was increased by a further 14% when the combination was occasionally completed with a short-term antibiotic or prolonged azathioprine therapy . The inestimable cases and those refractory to treatment made up the other 12% and among them are also the 23 colectomized patients . During the two decades 40 patients with Crohn type ileocolitis were treated . SASP administration by itself was sufficient in only one case among them . In 6 cases steroid, in 4 antibiotics, in 7 azathioprine and in 2 cases metronidazole treatment had to be introduced complementarily . The fact that 21 of the 40 patients had to be subjected to bowel resection in some phase of the disease, shows how impossible it is to evaluate the different therapeutic interventions.

Comp Biochem Physiol C, 1985, 81(2), 401 - 4
Actinomycin D and cycloheximide actions on activity of some intestinal enzymes of adult hamster; Andres MD et al.; Actinomycin D, at a dose of 0.25 micrograms/g body wt, produced slight increases in intestinal enzymatic activity on hamsters . At a high dose (1.5 micrograms/g body wt), actinomycin D produced inhibition of lactase activity, whereas maltase, sucrase and alkaline phosphatase activity decreased in males and increased in females . Cycloheximide (1.5 micrograms/g body wt), produced no changes in enzymatic activity . In the male and female hamster, the different actions of the antibiotic can be explained by the variations in the cortisol release produced by stress.

Virchows Arch B Cell Pathol Incl Mol Pathol, 1985, 48(3), 219 - 27
Fine structural aspects of the black thyroid induced by minocycline, and the effects of a low iodine diet, propylthiouracil, thyroxine tablet and TSH, on the black discoloration of the rat thyroid; Kurosumi M et al.; Fine structural aspects of the effect of minocycline, an antibiotic of the tetracycline group, on the rat thyroid were studied . In all the rats administered minocycline (100 mg/kg/day) for 21 days, diffuse black discoloration of the thyroid gland occurred . However, when the rats were fed on a low iodine diet, given propylthiouracil (PTU) or thyroxine tablet with minocycline the black pigmentation of the thyroid gland did not take place . On the other hand, black discoloration of the thyroid was accelerated in the rats administered TSH and minocycline simultaneously . Ultrastructurally, numerous dense bodies containing highly electron-dense deposits were seen in the supranuclear region of the follicular epithelial cells of the black thyroid . These dense bodies, which showed positive acid phosphatase activity, are considered to be lysosomes containing minocycline or its derivatives . It is speculated that minocycline is taken up into follicular epithelial cells with iodine, and that the black discoloration of the thyroid gland is intimately related to iodine metabolism.

Folia Haematol Int Mag Klin Morphol Blutforsch, 1985, 112(1), 208 - 18
{Bisalbuminemia . Critical review and report of a case of an acquired form in a myeloma patient}; Pola V et al.; Hitherto, bisalbuminemia (double albuminemia) was regarded as a rare finding in serum electrophoresis . In its first part, therefore, the present paper briefly refers to history, systematic, appearance, geography, genetics and laboratory problems of anomaly . By means of own observations made in an acquired form of bisalbuminemia in a patient with a myeloma, problems and practical significance of this serum protein anomaly are then discussed in a second part . This serum protein anomaly is likely to occur more frequently than hitherto assumed and after clarification it may contribute to increase our knowledge about indication and technique of the antibiotic therapy.

Acta Derm Venereol, 1985, 65(1), 43 - 52
Clinical manifestations of erythema chronicum migrans Afzelius in 161 patients . A comparison with Lyme disease; Asbrink E et al.; Clinical symptoms were studied in 161 consecutive patients with erythema chronicum migrans Afzelius and in a follow-up study signs of late manifestations were investigated . General symptoms such as headache, fever, myalgia and/or arthralgia were found in about half of the patients with a disease duration of less than or equal to 3 weeks . Three patients had coexisting lymphadenosis benigna cutis . Two untreated patients developed meningitis/meningoradiculitis and one untreated patient arthritis . The importance of a sufficient antibiotic therapy to prevent late manifestations is stressed . Although there are many similarities between erythema chronicum migrans Afzelius and Lyme disease, the results of the present study also point to differences . Multiple skin lesions, pronounced general symptoms, laboratory abnormalities and major symptoms from the joints were less common in patients with erythema chronicum migrans Afzelius than reported in patients with Lyme disease, but a prolonged course of the skin eruption was more common.

Cancer Res, 1985 Jan, 45(1), 213 - 6
Enhancement of mitomycin C cytotoxicity to hypoxic tumor cells by dicoumarol in vivo and in vitro; Keyes SR et al.; Previous work by our laboratories demonstrated that dicoumarol can increase the enzymatic activation of mitomycin C (MC) to alkylating species by tumor cell sonicates under hypoxic conditions . To determine whether this increased generation of reactive metabolites would result in increased cytotoxicity, we examined the effect of this combination on the viability of EMT6 cells treated in vitro under hypoxic and oxygenated conditions . Dicoumarol increased the cytotoxicity of MC to these neoplastic cells under hypoxic conditions and decreased the toxicity of the antibiotic to aerobic cells . These findings suggested that dicoumarol might enhance the toxicity of MC to the hypoxic cells of solid tumors, without increasing the toxic side effects of the antibiotic to the host . Treatment of EMT6 tumor-bearing animals with both dicoumarol and MC significantly decreased the survival of the radioresistant hypoxic tumor cells from that obtained with MC alone . In contrast, the leukopenia produced by the antibiotic was not exacerbated by the addition of dicoumarol . These results suggest that a treatment regimen combining dicoumarol and MC might be a useful adjunct to radiation therapy for the eradication of the radioresistant hypoxic cells in solid tumors.

Drugs Exp Clin Res, 1985, 11(1), 9 - 15
Experimental studies on aclacinomycin; Tone H et al.; Experimental features of aclacinomycin (ACM), a new antitumour antibiotic of the anthracycline group, are presented . ACM inhibited the growth of experimental mouse tumours and human cancer xenografts from various origins . In CDF1 mice with L1210 cells treated i.p . with ACM in combination with Ara-C for 10 days, a 459% ILS was observed, including 67% of 60-day survivors . The inhibition of RNA and DNA synthesis was examined in L1210 cells . The IC50 values of ACM for incorporations of {14C}-thymidine and {14C}-uridine were 0.30 and 0.038 microgram/ml respectively . The ratio of IC50 . DNA/RNA was 7.9, while with adriamycin (ADR) it was 2.5 . ACM showed no mutagenic activity in the Ames' test and the rec- assay . The cardiac toxicity of ACM was significantly lower than that of ADR . Lower ECG changes, a return to normal after discontinuation of the drug and slighter ultrastructural modifications of the myocardium were demonstrated in hamsters and rabbits . When administered to hamsters i.v . at 5 mg/kg, ACM was eliminated almost completely from the heart muscle after 2 h, while ADR remained at 8 micrograms/g even after 8 h.

Cornea, 1985-86, 4(4), 256 - 62
Two treatments of eye bank donor corneas; Farge EJ et al.; The many published studies on sterile procedures used by eye banks have included none until now on ways to optimize sterile handling of corneas procured in the morgues of forensic pathologists . The present study sought to discover if fewer positive cultures would be reported at the time of surgery from corneas which had been treated with an entire bottle of antibiotic (10 ml), as opposed to the more usual method of instilling 10 to 12 drops of antibiotic prior to the corneal excision . The result showed a marginal improvement of 3.1% fewer positive cultures when the entire bottle of antibiotic was used . The findings bolstered the theory that thorough and vigorous washing of the conjunctival sac prior to corneal removal is important and that positive cultures are no more likely when the cornea is shipped away from the eye bank than when used locally.

Chromosoma, 1985, 93(2), 165 - 8
SCE induction and harlequin staining in mycoplasma-contaminated Chinese hamster cells; White GR et al.; Chinese hamster V79 and CHO cells infected with Mycoplasma hyorhinis show elevated sister-chromatid exchange (SCE) levels but normal cell proliferation and levels of chromosomal aberrations when compared with uninfected cells . Harlequin staining patterns differ from those seen with uninfected cells at similar levels of bromodeoxyuridine (BrdUrd), indicating that BrdUrd is rapidly depleted from the medium by the mycoplasmal uridine phosphorylase and therefore becomes unavailable over the two cell cycles necessary for harlequin staining . Continuous treatment with the antibiotic minocycline restores the SCE level and harlequin staining to that seen in uncontaminated cells . The results suggest that mycoplasma infection should be suspected if harlequin staining patterns indicate a sudden decrease in incorporation of BrdUrd in cells grown in normal levels of BrdUrd.

J Membr Biol, 1985, 87(3), 233 - 9
Osmotic water permeability of small intestinal brush-border membranes; Worman HJ et al.; A stopped-flow nephelometric technique was used to examine osmotic water flow across small intestinal brush-border membranes . Brush-border membrane vesicles (BBMV) were prepared from rat small intestine by calcium precipitation . Scattered 500 nm light intensity at 90 degrees to incident was a linear function of the number of vesicles in suspension, and of the reciprocal of the suspending medium osmolality . When BBMV were mixed with hyperosmotic mannitol solutions there was a rapid increase in the intensity of scattered light that could be fit to a single exponential function . The rate constant for vesicle shrinking varied with temperature and the size of the imposed osmotic gradient . At 25 degrees C and an initial osmotic gradient of 50 mOsm, the rate constant was 1.43 +/- 0.044 sec-1 . An Arrhenius plot of the temperature dependence of vesicle shrinking showed a break at about 25 degrees C with an activation energy of 9.75 +/- 1.04 kcal/mole from 11 to 25 degrees C and 17.2 +/- 0.55 kcal/mole from 25 to 37 degrees C . The pore-forming antibiotic gramicidin increased the rate of osmotically driven water efflux and decreased the activation energy of the process to 4.51 +/- 0.25 kcal/mole . Gramicidin also increased the sodium permeability of these membranes as measured by the rate of vesicle reswelling in hyperosmotic NaSCN medium . Gramicidin had no effect on mannitol permeability . Assuming spherical vesicles of 0.1 micron radius, an osmotic permeability coefficient of 1.2 X 10(-3) cm/sec can be estimated for the native brush-border membranes at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

J Gynecol Obstet Biol Reprod (Paris), 1985, 14(6), 683 - 7
{Prevention of peritoneal adhesions by local treatments . Experimental study in the rat}; Querleu D et al.; Those local treatments that are most used clinically for the prevention of adhesions in the pelvis have been evaluated experimentally using peritoneal abrasion in the rat . In a first experiment these products, namely dexamethasone, high molecular weight dextran, and noxytioline, were compared with a saline solution on the one hand which confirmed the effect of these substances in preventing adhesions, and on the other hand showed that noxytioline was about as effective as dextran 70 and better than corticosteroids . The score for adhesions that were found were; in the control series an average of 9.25, in the dexamethasone series 6, in the dextran 70 series 4.1 and in the noxytioline series 4.00 . This last substance, which has been for less broadly studied than dextran, was then made the subject of a second experiment carried out in the same way as the first, and showing that the anti-adhesion effect was not something that was added on to its anti-bacterial effect because noxytioline alone was more effective than a broad spectrum antibiotic by itself, and adding the two together gave a still better result . It would seem to us that using noxytioline and dextran 70 together does not improve the results achieved by using each substance by itself.

Hear Res, 1985, 20(1), 37 - 43
Abolition of the negative endocochlear potential as a consequence of the gentamicin-furosemide interaction; Lee SJ et al.; The DC endocochlear potential and the AC cochlear potential in response to a 4 kHz tone were recorded in pigmented guinea pigs before and during ototoxic damage induced by sequential administration of the aminoglycoside antibiotic, gentamicin, and the loop diuretic, furosemide . Within 4 h significant diminution of the amplitude of the AC cochlear potential was accompanied by an almost complete abolition of the negative diffusion potential revealed by either furosemide administration or terminal anoxia . Thus, one of the effects of this interaction appears to involve a reduction in the potassium permeability of the cochlear partitions.

Eur Biophys J, 1985, 12(2), 67 - 73
Molecular shape and dipole moment of alamethicin-like synthetic peptides; Rizzo V et al.; The peptides Boc-(L-Ala-Aib-L-Ala-Aib-L-Ala)n-OMe, with n = 2 (P10) and n = 4 (P20), have been synthesized as purely hydrophobic models of the antibiotic alamethicin, which is known to be a voltage-dependent pore former in membranes and is apparently alpha-helical in lipophilic media . These peptides were investigated in 1-octanol, a solvent which resembles the membrane environment . From dielectric dispersion studies quantitative information on the molecular shape and dipole moments could be derived . Further independent data concerning conformation and extent of aggregation of the peptides were obtained by circular dichroism and ultracentrifuge measurements . The results suggest that the peptides assume the form of elongated particles having a significant amount of ordered secondary structure and carrying a dipole parallel to the long axis . Apparently the monomeric peptide molecules undergo, to some extent, a head-to-tail aggregation which is slightly enhanced at lower temperatures . Based on the high-frequency parts of the dielectric dispersion curves the lengths, diameters, and dipole moments of the monomer particles have been determined as 22.5A, 10A, 36 D (P10) and 28.5A, 12A, 64D (P20).

Tierarztl Prax Suppl, 1985, 1, 123 - 31
{Diagnosis of prostatic diseases in the dog using ultrasonics}; Fritsch R et al.; The use of sonography in diagnosing prostate gland diseases has proven very helpful . In contrast to x-raying, it allows the exact determination of the size and position of the prostate, without invasive methods or the danger of side-effects . It also allows the evaluation of its inner construction . For the veterinarian, this is important when weighing the different therapeutic possibilities . Through sonographic findings the kind, extent and localisation of necessary surgery can be decided before hand . The prognosis is facilitated and a continuous control of the intraprostatic process can be carried out, (for example; regression after castration, marsupialisation or antibiotic therapy) . One must point out that, when judging prostate gland diseases, the diagnosis should never be made solely on sonographic results, but only in combination with clinical and laboratory examinations.

Arch Int Pharmacodyn Ther, 1985 Jan, 273(1), 167 - 76
The mechanism of gentamicin-inhibited insulin release by isolated islets; Boschero AC et al.; These experiments were performed in order to determine the mechanism of action of the aminoglycoside antibiotic gentamicin on insulin release by isolated islets . Gentamicin significantly reduced the insulin release in the absence as well as in the presence of increasing concentrations of glucose . This effect was immediate and promptly reversible . In the presence of glucose plus high concentrations of K+ the antibiotic did not affect insulin secretion . Gentamicin did not change 86Rb efflux from perifused islets or the glucose metabolism in incubated islets . These data show that gentamicin does not alter the recognition and subsequent metabolism of glucose, and the system responsible for insulin secretion . We suggest that gentamicin reduces glucose-induced insulin release by blocking the entry of Ca2+ into the B-cells.

Biochem Biophys Res Commun, 1984 Dec 28, 125(3), 895 - 901
Cloning and expression in Streptomyces lividans of a paromomycin phosphotransferase from Streptomyces rimosus Forma paromomycinus; Perez-Gonzalez JA et al.; The paromomycin producing organism Streptomyces rimosus forma paromomycinus is resistant to this antibiotic and contains a phosphotransferase which inactivates paromomycin . The gene encoding this enzyme has been inserted in the Streptomyces vector pIJ702 and then cloned in Streptomyces lividans, selecting for paromomycin-resistance . Three plasmids have been isolated and one of them, pMJ1, contains a 2.2 kb insert with a single HindIII restriction site . Insertion of foreign DNA in this site blocks the expression of the phosphotransferase enzyme indicating that it is within the cloned gene . These findings provide a new dominant selective marker for Streptomyces cloning vectors with the versatility of insertional inactivation.

J Biol Chem, 1984 Dec 25, 259(24), 14997 - 9
Suppression of placental alkaline phosphatase biosynthesis by tunicamycin; Ito F et al.; Placental alkaline phosphatase activity and immunoreactivity were inhibited in a parallel fashion in choriocarcinoma cells by tunicamycin, a protein glycosylation inhibitor . Tunicamycin suppressed placental alkaline phosphatase biosynthesis in addition to inhibiting protein glycosylation in general . An anti-placental alkaline phosphatase-precipitable polypeptide of 58,000 daltons was formed in the presence of this antibiotic . The 58,000-dalton polypeptide had a degradation rate similar to that of the glycosylated phosphatase monomer from control cultures . Tunicamycin suppressed placental alkaline phosphatase mRNA activity leading to the observed decrease in biosynthesis.

Am J Med, 1984 Dec 21, 77(6A), 4 - 6
Penetration of cefmenoxime into serum, gynecologic tissues, and heart valves; Daschner FD et al.; Twenty-nine women received 7 g of cefmenoxime before abdominal or vaginal hysterectomy; 20 adult patients received 2 g of cefmenoxime 24 hours and immediately before open heart surgery . In the gynecologic patients, peak cefmenoxime serum concentrations of 23.4 mg/liter were reached within one to two hours after administration of the antibiotic . Cefmenoxime concentrations in myometrium, endometrium, and salpinges also reached their peak one to two hours after administration . Two to three hours later tissue concentrations varied between 1.1 and 5.2 micrograms/g; four hours after application, tissue concentrations were below detectable levels . Cefmenoxime plasma and tissue concentrations were significantly higher in patients undergoing open heart surgery . Subcutaneous tissue and muscle concentrations varied between 2.7 and 38.0 micrograms/g . Cefmenoxime concentrations in cardiac valvular tissue were higher than those in muscle and fat.

Biochim Biophys Acta, 1984 Dec 19, 778(3), 435 - 42
Interaction of amphotericin B with membrane lipids as viewed by 2H-NMR; Dufourc EJ et al.; The effects of amphotericin B upon the organization and dynamics of multibilayer membranes of dimyristoylphosphatidylcholine (DMPC) were investigated by means of 2H-NMR . At high amphotericin B concentrations (30 mol% with respect to the lipid) and at temperatures above 25 degrees C, DMPC experiences two different environments which are in slow exchange on the 2H-NMR time scale . In one of these, the lipid is immobilized by the antibiotic, in a molar ratio of approximately 1:1, whereas the lipid unsequestered by amphotericin B is more ordered than in its pure state . This ordering effect is perceived at relatively low antibiotic doses (4%) . The local lipid order, and the relative percentage, of sequestered DMPC, are temperature-independent (up to 65 degrees C), whereas the ordering of the unsequestered lipid domain is not . The perturbation induced by amphotericin B is manifest similarly at the edges as well as in the center of the bilayer . Antibiotic addition leads to large decreases in the transverse relaxation time, T2, of the labelled lipid, but not in the spin-lattice relaxation time, T1 . This indicates an increased density of slow motional modes and little change in rapid motions.

Biochemistry, 1984 Dec 18, 23(26), 6697 - 703
Cross-linking of streptomycin to the 30S subunit of Escherichia coli with phenyldiglyoxal; Melancon P et al.; {3H}Dihydrostreptomycin was covalently linked to the 30S subunit of Escherichia coli K12A19 with the bifunctional cross-linking reagent phenyldiglyoxal . The cross-linking was abolished under conditions that prevent the binding of streptomycin, which indicates that the cross-linking occurs at the specific binding site of streptomycin . The cross-linking involved 16S RNA and the ribosomal proteins S1, S5, S11, and S13 . This suggests that the streptomycin binding site is located in the upper part of the 30S subunit, facing the 50S subunit . Unexpectedly, the same extent and pattern of cross-linking were observed with the 30S subunits from a streptomycin-resistant mutant . We have shown previously that streptomycin induces conformational changes in the ribosomes from sensitive bacteria but not from streptomycin-resistant mutants . From this and from the results in the present study, it is suggested that the binding of streptomycin to streptomycin-sensitive ribosomes is a two-step reaction wherein an initial loose interaction at the antibiotic binding site is followed by a conformational rearrangement of the ribosomal particle . The second step would tighten the association with streptomycin and cause interference with protein synthesis . That step would be lacking in streptomycin-resistant mutants.

Eur J Biochem, 1984 Dec 17, 145(3), 579 - 86
Kinetic evidence for redistribution of actinomycin molecules between potential DNA-binding sites; Fox KR et al.; The kinetics of interaction between actinomycin D and DNA have been measured by stopped-flow and detergent-dissociation methods . The results are consistent with a model in which the antibiotic initially binds to many sequences on the heterogeneous DNA lattice and subsequently 'shuffles' between the available sites until a thermodynamically determined optimal state of binding is attained . The amplitudes of the two slowest components in the reaction with calf thymus DNA do not vary in parallel as the total level of antibiotic binding is increased; they appear to reflect directly the redistribution of antibiotic molecules along the DNA lattice . The dissociation profile is shown to depend upon the time for which the antibiotic and DNA are premixed, so that for short mixing times a higher proportion of the decay is represented by faster-dissociating species . The rate of appearance of the slowest-dissociating species correlates well with the slowest optical change in the association reaction . Stopped-flow experiments indicate that the antibiotic first binds to sites on natural DNA with an average association constant of 4 X 10(3) M-1 and that it subsequently migrates to sites with higher affinity . Similar experiments performed with poly(dG-dC) are less easily interpreted and seem to indicate that conformational changes or cooperative effects can also occur.

Experientia, 1984 Dec 15, 40(12), 1357 - 62
Malaria prophylaxis in travellers: the current position; Sturchler D; Malaria prevention is a main challenge for physicians, nurses, health officers and tour operators . The attack rate of malaria in travellers is 1-10/10,000 departures, and the case fatality rate of imported malaria is around 0.5/100 . Travellers should be informed about the risk they are going to take, how to protect against mosquito bites, about the antimalarials they will have to take and what to do when a malaria breakthrough should occur . The 4-aminoquinolines (chloroquine, amodiaquine) remain the drug of choice for the prevention of Plasmodium vivax and of sensitive P . falciparum infections . The problem is to find an effective and safe drug combination for travellers to areas where P . falciparum is either resistant to chloroquine, to Fansidar (the combination of pyrimethamine plus sulfadoxine) or to both . These travellers will probably best be protected by an individually tailored drug combination, which includes amodiaquine or mefloquine as baseline drugs, and a supplementation with Fansidar, Maloprim (the combination of pyrimethamine with dapsone), paludrine or an antibiotic.

Nucleic Acids Res, 1984 Dec 11, 12(23), 9165 - 77
Infrared linear dichroism of oriented DNA-ligand complexes prepared with the wet-spinning method; Fritzsche H et al.; Oriented DNA films prepared by the wet-spinning technique have been complexed with several ligands: the anthracycline antibiotic violamycin BI, the dipeptide L-carnosine, and the oligopeptide antibiotic netropsin . The formation of the DNA-ligand complexes is accompanied by dramatic changes of the conformational flexibility of DNA . The B-A transition which occurs usually between 80% and 70% relative humidity (RH) is more or less suppressed by the ligands . Violamycin BI at a total ligand per DNA base pair ratio, rt, of approximately 0.03 and L-carnosine at rt approximately 1.5 inhibit the B-A transition of approximately 18 and approximately 0.25 base pairs per ligand molecule, respectively . Netropsin at rt = 0.2 induces a very stable B-DNA even at rather low RH (23%) . The total hydration of this complex is significantly higher than for a drug-free DNA film . Netropsin-DNA complexes at rt of 0.02 and 0.01 result in an inhibition of approximately 45 base pairs per drug molecule with respect to the B-A transition.

J Comp Neurol, 1984 Dec 10, 230(3), 437 - 43
The distribution of filipin-sterol complexes in photoreceptor synaptic membranes; Cooper NG et al.; The polyene antibiotic filipin, which binds to membrane sterols, has been used to investigate the relative distribution of cholesterol at photoreceptor synaptic junctions in the chick retina . Following anesthesia and aldehyde perfusion fixation, the retina is removed and immersed in fixative solution containing the filipin for 36-48 hours . The retinas are then processed for freeze-fracture . Electron microscopy of freeze-fracture replicas demonstrates that the filipin-sterol complexes are not evident between intramembrane particles of the presynaptic and postsynaptic particle arrays that are present at ribbon and basal junctions . In contrast, the synaptic vesicle fusion zone of ribbon junctions contains large numbers of filipin-sterol complexes which are observed merging with the free margins of the presynaptic particle array . There is a scarcity of such complexes, however, around the free margins of basal junction presynaptic particle arrays . These latter sites do not contain a vesicle fusion zone . Particle-poor areas of membrane that surround postsynaptic particles arrays of ribbon and basal junctions also do not contain filipin binding sites . The nonsynaptic membrane of photoreceptor terminals contains large numbers of filipin-sterol complexes, less tightly packed than in the synaptic vesicle fusion zone . Coated vesicle fusion sites in the presynaptic membrane contain groups of intramembrane particles but the filipin-sterol complexes are excluded from these sites . The observations suggest that synaptic membrane domains which interact with cytoskeletal components, such as clathrin and pre- and postsynaptic densities contain less cholesterol than other domains such as the synaptic vesicle fusion zones.

Cell Differ, 1984 Dec, 15(2-4), 93 - 7
DNA transformation of a pluripotent mouse embryonal stem cell line with a dominant selective marker; Wobus AM et al.; The mouse embryonal stem cell line BLC 1 growing on feeder layer was treated with a calcium phosphate/DNA precipitate prepared with DNA of plasmid pAG60 which harbors the Tn5-derived neo gene, thus encoding resistance to G418, an aminoglycoside antibiotic . Transfection performed on feeder layer resulted in the formation of G418-resistant clones T1 and T2/K26 . The stable integration of the transformed neo gene was confirmed by dot hybridization in all descendant cultures of clones T1 and T2/K26 as well as in the tumors derived from them . In vivo and in vitro differentiation revealed the pluripotent status of the transformants . Tumors derived from T1 and T2/K26 contained various tissues with derivatives of all three primary germ layers.

Laryngoscope, 1984 Dec, 94(12 Pt 1), 1576 - 9
Necrotizing fasciitis as a lethal complication of peritonsillar abscess; Wenig BL et al.; Abscesses of the peritonsillar region rarely lead to serious complications . Incision and drainage, antibiotic therapy, and subsequent tonsillectomy is the accepted method of treatment . Two cases of fatal necrotizing fasciitis following peritonsillar abscess are presented . The entity of necrotizing fasciitis in the head and neck is discussed with respect to its presentation, diagnosis, and treatment.

Geburtshilfe Frauenheilkd, 1984 Dec, 44(12), 792 - 5
{Short-term prevention with cefoxitin in cesarean section}; Heilmann L et al.; In a preliminary prospective study, the febrile morbidity of 60 patients after Caesarean section was determined to investigate the prophylactic effect of a single-dose cefoxitin-application (2 g) intravenously at the time of induction of anaesthesia . Patients were randomly assigned to either the cefoxitin group or a control group without the antibiotic . Each group consisted of 30 patients . Although the numbers of patients were small, a statistically significant reduction (p less than 0.05) of febrile days was found for the cefoxitin group . As compared to previous studies with a three-dose regimen of cefoxitin, the per cent reduction rate of febrile morbidity was similar . In cases with certain risk profiles, such as premature rupture of the membranes or prolonged delivery, a single-dose appears to suffice and is therefore indicated.

Contraception, 1984 Dec, 30(6), 535 - 44
Influence of removal of intrauterine contraceptive devices on colonisation of the cervix by actinomyces-like organisms; Mao K et al.; PIP: An overall prevalence rate of actinomyces-like organisms (ALO) in cervical smears of IUD users of 3% (79/2734) was found, with a rate of 2% and 22.6% for copper and inert IUD users . Although the users of the inert IUDs were older, and their devices had been in situ longer, these factors did not account for the significant differences between the 2 types of IUD . 55 patients were counseled and given a leaflet on ALO . 14 IUD users with ALO positive smears who had their devices removed had mild or moderate pelvic pain or discharge . 6 others who were asymptomatic had the IUD removed at their own request . All 55 patients were reexamined 6 months-1 year later and a smear was repeated . Only 1 woman required later removal of the IUD because of dyspareunia with pelvic tenderness . After IUD removal, and without antibiotic therapy, ALO colonization was no longer found 6-12 months later in 100% (20/20) of the cases . This even included the 7 women who had had new copper IUDs inserted immediately after removal of the index device .

Jpn J Antibiot, 1984 Dec, 37(12), 2519 - 30
{Pharmacokinetic studies of cefbuperazone in the field of gynecology}; Seiga K et al.; Cefbuperazone (CBPZ), a new cephamycin antibiotic, was studied for the distribution in the genital organs and the excretion to the pelvic dead space exudate by bioassay, and the following results were obtained . CBPZ was rapidly distributed into the various tissues by intravenous drip infusion of 0.5 g and 1.0 g for 1 hour . Those levels depended on serum levels and the ratios (tissue level/serum level) were about 15-25% . Obvious dose response between 0.5 g and 1.0 g of CBPZ was recognized for serum levels as well as tissue levels . Serum and tissue levels were respectively analyzed by two- and three-compartment open model . Consequently, the obtained simulation curve approximated to the observed results . The simulation curve and pharmacokinetic parameters by one-compartment open model were appropriate for CBPZ levels in the pelvic dead space exudate.

J Antibiot (Tokyo), 1984 Dec, 37(12), 1587 - 95
B-factor, an essential regulatory substance inducing the production of rifamycin in a Nocardia sp; Kawaguchi T et al.; "Curing" treatment of a rifamycin-producing Nocardia sp . resulted in a mutant deficient in the synthesis of antibiotics . This deficiency was reversed in a medium containing yeast extract . The active substance, named B-factor, which induced rifamycin production in the mutant was purified from yeast extract, and its structure, 3'-(1-butylphosphoryl) adenosine, was determined by structural analysis and chemical synthesis . An extremely low concentration of B-factor (10 ng/ml) caused recovery of rifamycin B synthesis in the mutant and stimulated synthesis of the antibiotic in the parental strain.

Br J Obstet Gynaecol, 1984 Dec, 91(12), 1181 - 7
Pelvic inflammatory disease after hysterosalpingography associated with Chlamydia trachomatis and Mycoplasma hominis; Moller BR et al.; A total of 116 women were referred for hysterosalpingography because of primary or secondary infertility . Chlamydia trachomatis was isolated from the cervix of four (3.4%) of the patients whereas Mycoplasma hominis was isolated from 39 (33.6%) of them . Four patients developed acute pelvic inflammatory disease after hysterosalpingography; two of them were chlamydia culture-positive and developed a significant chlamydial antibody response during the course of the disease . One of the other two patients, who developed upper genital-tract infection, was culture positive for M . hominis and developed a significant antibody response to this micro-organism . The results indicate that C . trachomatis should be sought in patients before hysterosalpingography and, if detected, appropriate antibiotic cover should be instituted before the procedure.

Br J Haematol, 1984 Dec, 58(4), 633 - 40
Assessment of the drug sensitivity of acute nonlymphocytic leukaemia using the in vitro clonogenic assay; Preisler HD et al.; The ability of an in vitro clonogenic drug sensitivity assay to predict the outcome of therapy for acute nonlymphocytic leukaemia was evaluated using marrow cells obtained from previously untreated or first relapsed patients treated with either cytosine arabinoside/anthracycline antibiotic or high dose cytosine arabinoside remission induction therapy . While the per cent of leukaemic cells killed in vitro was correlated with the outcome of therapy, this drug sensitivity assay provided little or no clinically useful information.

Arch Ophthalmol, 1984 Dec, 102(12), 1825 - 9
A fresh look at iontophoresis; Hughes L et al.; The rate of penetration of fluorescein and gentamicin ions into the anterior chamber of the rabbit was increased more than 100-fold by the passage of 1 mamp; the amount of drug that penetrates is better controlled by iontophoresis than by instillation . The potential value, the safety and the limitations of this procedure are discussed, and a theoretical basis for the increase is provided . Practical methods of using iontophoresis in the clinic are described . A 30-s application should result in a therapeutic level of the antibiotic in the anterior segment over a 12-hour period in eyes with an intact epithelium.

Arch Surg, 1984 Dec, 119(12), 1372 - 8
A proposed classification of intra-abdominal infections . Stratification of etiology and risk for future therapeutic trials; Meakins JL et al.; Serious studies of ultra-abdominal infections have yielded a mortality that ranges from 3.5% (a composite of antibiotic studies evaluating 1,275 patients) to more than 60% in studies of multiple-organ failure . In reviewing these studies, it is apparent that under the umbrella of "serious intra-abdominal infection," different diseases, processes, and patients are being studied . We define a binomial classification incorporating both an anatomic and a functional approach to intra-abdominal infection . There are ten etiologic classifications of intra-abdominal infections combined with an acute physiologic score (APS), measuring severity of illness, in three gradations . In the patient with undifferentiated intra-abdominal sepsis, the patient will be in class I, II, III, or IV, with a score, A, B, or C, added . Each of the groups V-X, defining a specific infectious category, can also use the APS, which has been verified in patients in intensive care and in those with intra-abdominal infection . It is anticipated that using this approach will provide a technique to evaluate patient groups uniformly in which drug or technical approaches to the management of intra-abdominal infections are being studied . The patients being studied will be more clearly defined, and studies will be comparable from one center to another.

Exp Parasitol, 1984 Dec, 58(3), 356 - 64
Tritrichomonas foetus: localization of filipin-sterol complexes in cell membranes; Benchimol M et al.; The polyene antibiotic, filipin, was used as a probe for the detection of sterols in the freeze-fractured plasma membrane and the flagellar membranes of the pathogenic protozoa, Tritrichomonas foetus . A homogeneous distribution of filipin-sterol complexes was seen throughout the plasma membrane, and the membrane of the three anterior and the one recurrent flagella . No or very few filipin-sterol complexes were observed in some specialized regions such as the base of the flagella (necklace), the portion of the recurrent flagellum, and that part of the cell body to which the flagellum was attached . The density of filipin-sterol complexes varied from one cell to the other . In some cells, about 205 complexes/micron 2 were seen . A larger number of filipin-sterol complexes were observed on both faces of the membrane of cytoplasmic structures, probably corresponding to vacuoles . No complexes were seen in the nuclear membrane and in the membrane of the endoplasmic reticulum . Very few or no complexes were observed in the membrane of the hydrogenosomes . Treatment of living cells with filipin induced aggregation of filipin-sterol complexes at some points of the plasma membrane.

Cancer Res, 1984 Dec, 44(12 Pt 1), 5638 - 43
Role of NADPH:cytochrome c reductase and DT-diaphorase in the biotransformation of mitomycin C1; Keyes SR et al.; Hypoxic cells of solid tumors are difficult to eradicate by X-irradiation or chemotherapy; as an approach to this problem, our laboratories are investigating the effects of the bioreductive alkylating agent mitomycin C (MC) on hypoxic cells . This antibiotic was preferentially toxic to EMT6 mouse mammary tumor cells and V79 Chinese hamster lung fibroblasts under hypoxic conditions, but it was equitoxic to Chinese hamster ovary cells in the presence and absence of oxygen . All cell lines catalyzed the formation of reactive metabolites under hypoxic conditions and contained NADPH:cytochrome c reductase and DT-diaphorase, two enzymes which may be responsible for the cellular activation of MC . Although a correlation existed between enzymatic activities and the formation of reactive metabolites from MC, there was no correspondence between these parameters and the degree of cytotoxicity expressed by MC under hypoxic conditions . Purified NADPH:cytochrome c reductase reduced MC in the absence of oxygen, with addition of cytochrome P-450 enhancing, but not participating directly in, the reduction reaction . Addition of NADP+ to cell sonicates substantially reduced NADPH:cytochrome c reductase activity, while the formation of reactive metabolites was affected only slightly; converse results were observed using mersalyl . Exposure of cell sonicates to dicumarol inhibited DT-diaphorase activity, while the rate of formation of reactive metabolites of MC was enhanced . The findings suggest that NADPH:cytochrome c reductase and some as yet to be identified enzyme(s) are important for the reductive activation of MC . DT-diaphorase and cytochrome P-450 are not directly involved in the activation of MC, but they appear to modulate the degree of activation to reactive species, which are presumably responsible for the observed cytotoxicity.

Drug Intell Clin Pharm, 1984 Dec, 18(12), 984 - 7
Sequential ventricular fluid concentrations of ceftazidime--report of three cases; Polk RE et al.; Three adult subjects, each with a ventriculostomy, received ceftazidime 2g iv q8h for three doses . Serial samples of serum and CSF ventricular fluid were obtained following the third dose; ceftazidime concentrations were measured by high pressure liquid chromatography . In one patient without inflammatory cells in the CSF, ceftazidime CSF concentrations were only approximately 0.3 micrograms/ml . In two other patients who had inflammatory cells and blood in the CSF, concentrations of ceftazidime in ventricular fluid demonstrated a slow rise and decline over an eight-hour period . Although contamination of the CSF by blood in these two patients confounds the interpretation of the concentrations achieved, it is concluded that obtaining serial samples of CSF from a ventriculostomy offers a more realistic appraisal of the dynamics of antibiotic penetration compared with the single-point method.

Arch Surg, 1984 Dec, 119(12), 1410 - 8
Evaluation of naloxone for therapy of Escherichia coli shock . Species differences; Hinshaw LB et al.; Dogs and baboons were infused intravenously (IV) with Escherichia coli and treated with the opiate antagonist, naloxone hydrochloride, and the antibiotic, gentamicin sulfate, to determine the therapeutic efficacy of naloxone . Naloxone hydrochloride (2 mg/kg) was injected IV when one fourth of the E coli had been infused and then infused at 2 mg/kg/hr (six hours for dogs and 12 hours for baboons) . Four of five naloxone-treated dogs survived permanently (greater than seven days), while all dogs that were given only E coli died . Arterial BP, blood glucose levels, PCO2, and PO2 were supported at higher levels and lesions of the gastrointestinal tract were prevented in naloxone-treated dogs . A steady decline in blood glucose levels after an initial hyperglycemia was observed in naloxone-treated baboons, indications of peripheral vasoconstriction were noted, and all baboons died within 42 hours.

Arch Surg, 1984 Dec, 119(12), 1400 - 4
Ambulatory peritoneal dialysis . Exploratory laparotomy for peritonitis; Schulak JA et al.; We present our experience with performing an exploratory laparotomy for peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) . Six of 134 patients undergoing CAPD during the study period underwent surgical intervention because of abdominal sepsis . Two patients had bacterial peritonitis without abscess formation or evidence of visceral perforation and they recovered readily and, in retrospect, may not have required an operation . Of the three patients with fungal abscesses, two died of subsequent bacterial sepsis, while one patient survived, albeit after drainage of a recurrent pelvic abscess . One patient died because of extensive intestinal gangrene that was misdiagnosed as CAPD-related peritonitis initially . Our experience with these cases suggests that fungal peritonitis is a life-threatening complication that may result in both formation of an abscess and death . Therefore, it warrants aggressive antifungal chemotherapy and surgical intervention should an abscess be discovered . In contrast, bacterial peritonitis should be treated with appropriate antibiotic regimens until adequate evidence indicating the presence of a surgical condition is obtained.

Surg Gynecol Obstet, 1984 Dec, 159(6), 549 - 52
Extraperitoneal versus transperitoneal drainage of the intra-abdominal abscess; Stone HH et al.; Controversy as to whether the intra-abdominal abscess should be drained extraperitoneally or through formal laparotomy still rages . Arguments for a transperitoneal approach include no need to identify specific locus preoperatively and uniform drainage of all abscesses, especially any otherwise unrecognized pus collection . Proponents for the extraperitoneal route stress failure to contaminate previously uninvolved peritoneal spaces and more reliable avoidance of injury to intestine, predisposing to subsequent intestinal fistula . To resolve this impasse, a prospective study of each method was based upon a schedule of previously randomized treatment options . After 32 months of study, 60 patients had been enrolled without obvious differences between treatment groups with respect to demographic features, preoperative definition and locus of infection, precipitating cause of sepsis, associated diseases, responsible bacteria and antibiotic therapy . With the transperitoneal approach, five patients had hollow viscus injury, while seven eventually had an intestinal fistula develop, causing major problems in four . Despite no obvious intestinal injury with the extraperitoneal route, two transient intestinal fistulas did occur . Seven patients drained transperitoneally had additional abscesses discovered, yet another operation was required to drain at least one complicating abscess in seven of this same group . With the extraperitoneal route, only two patients needed reoperation to drain another abscess . Although there were more deaths and complications in the group drained transperitoneally, morbidity (47 per cent) and mortality (7 per cent) were not significantly different statistically . Such data refute the professed superiority of a transperitoneal approach to intra-abdominal abscess drainage, both from need to reoperative for second abscess as well as incidence of latter intestinal fistula . Best results were noted with abscess identification through computerized tomography followed by extraperitoneal drainage.

Blood, 1984 Dec, 64(6), 1146 - 58
T gamma-lymphoproliferative disease and related disorders in humans and experimental animals: a review of the clinical, cellular, and functional characteristics; Reynolds CW et al.; T gamma lymphocytes are those lymphocytes that express receptors for both the Fc portion of IgG and sheep erythrocytes . A very high proportion of normal T gamma lymphocytes are large granular lymphocytes (LGL), the cell responsible for most, if not all, natural killer (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) in humans, rats, and mice . In general, these cells are large lymphocytes with prominent azurophilic granules in the cytoplasm . Recently, a group of lymphoproliferative disorders made up predominantly of T gamma lymphocytes has been described . The most common and best studied of these disorders we refer to as "chronic T gamma-lymphoproliferative disease" (T gamma-LPD) . In most cases, this disease represents the abnormal expansion of LGL, which is reflected by an increase in functionally active NK or ADCC effector cells . The chronic T gamma-LPD lymphocytes are generally characterized as E- and EA-rosette positive, acid-phosphatase, and beta-glucuronidase positive and express the pan-T antigens OKT3/Leu-4, OKT11/Leu-5, the suppressor-associated antigens OKT5,8/Leu-2, and the NK-associated antigens Leu-7/HNK-1 . Typically, the patients are older, predominantly males and characteristically have a lymphocytosis of predominantly T gamma lymphocytes with lymphocyte infiltration of the bone marrow and often the spleen . While chronic T gamma-LPD is not usually an aggressive disease, the patients are often neutropenic and have recurrent bacterial infections requiring antibiotic therapy . Some patients have benefited from cytotoxic chemotherapy., but most patients have not required chemotherapy . An experimental LGL leukemia in F344 rats appears morphologically, functionally, and clinically similar to the human chronic T gamma-LPD and serves as an experimental model for further examining the ontogeny and function of LGL and may be applicable for exploring new and more effective means for the treatment of patients with chronic T gamma-LPD.

HNO, 1984 Dec, 32(12), 511 - 4
{Granulation tumor of the orbit following ointment treatment of the maxillary sinus}; Brusis T; Attempts to instil an antibiotic ointment into the right maxillary sinus led to the development of a granuloma of the lower eyelid and orbit and the tumour had to be resected . Retroposition of the rectus inferior muscle was carried out by the ophthalmologist to eradicate double images caused by scars . The injection of antibiotic ointments into the maxillary sinus is dangerous.

Mol Cell Biol, 1984 Dec, 4(12), 2929 - 31
Hygromycin B phosphotransferase as a selectable marker for DNA transfer experiments with higher eucaryotic cells; Blochlinger K et al.; The DNA coding sequence for the hygromycin B phosphotransferase gene was placed under the control of the regulatory sequences of a cloned long terminal repeat of Moloney sarcoma virus . This construction allowed direct selection for hygromycin B resistance after transfection of eucaryotic cell lines not naturally resistant to this antibiotic, thus providing another dominant marker for DNA transfer in eucaryotic cells.

Jpn J Antibiot, 1984 Dec, 37(12), 2364 - 70
{Fundamental and clinical studies of ceftriaxone in the field of obstetrics and gynecology}; Horii T et al.; Fundamental and clinical studies on ceftriaxone (Ro 13-9904, CTRX), a new cephem antibiotic, were carried out with the following results . Following each 1.0 g of drip infusion, transfer of CTRX to female genital organs was found to be excellent . Transfer of CTRX to exudate of the pelvic dead space was also excellent . And high concentration of CTRX was kept for long time after administration . CTRX was given to 7 cases . It was effective for 5 cases and ineffective for 2 cases . The above results demonstrated that CTRX is a safe and effective drug.

Jpn J Antibiot, 1984 Dec, 37(12), 2304 - 19
{Pharmacokinetics and clinical studies on ceftriaxone in the field of obstetrics and gynecology}; Cho N et al.; Ceftriaxone (Ro 13-9904, CTRX), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained . The absorption and tissue penetration of CTRX into intrapelvic genital organs were good . The peak serum level in the uterine artery after a single intravenous injection and that after an intravenous drip infusion for 30 approximately 60 minutes, both with 1 g, were 162.5 micrograms/ml and 84.4-93.8 micrograms/ml, respectively . High concentrations were obtained also in genital organ tissues; the maximum concentration was 93.8 micrograms/g by intravenous injection and 56.3-59.4 micrograms/g by intravenous drip infusion . Changes in the tissue concentration were similar to those in the serum, the level over MIC80 against main pathogenic organisms being maintained for a long time . The penetration of CTRX into intrapelvic dead space exudate was good . The level reached a peak of 18.8 micrograms/ml 2 hours after an intravenous injection with 1 g and 13.3 micrograms/ml after 12 hours, while the level over MIC80 against main pathogenic organisms was maintained for a long time . CTRX was effective in 15 out of 16 cases (93.8%) with gyneco-obstetric infections such as intrauterine, intrapelvic, adnexal infections, and postoperative would infections, administered with 1 g twice a day . No side effects were observed.

Biochem Pharmacol, 1984 Dec 1, 33(23), 3779 - 86
Studies on the action of nystatin on cultured rat myocardial cells and cell membranes, isolated rat hearts, and intact rats; Aszalos A et al.; The action of nystatin, a polyene antibiotic, was studied in rat myocardial cells, isolated rat hearts, and intact rats . Myocardial cells responded to 10 and 25 micrograms nystatin/ml with arrhythmias that could be minimized by elevated concentrations of K+ and Mg2+ or reversed by washing the cells . Similarly, the isolated heart responded to 100 micrograms nystatin/ml with arrhythmias that could be tempered by addition of elevated concentrations of K+ and Mg2+ . The i.v . injection of the drug caused heart failure in intact animals at the 4-mg/kg dose level . At the subcellular level, nystatin made the myocardial cell membranes more rigid, as measured by electron spin resonance spectrometry . These findings indicate a parallel between physiocochemical changes caused by nystatin in the myocardial cell membrane and the biological changes caused by this drug in myocardial cells, isolated heart, and heart of the intact animal.

Exp Cell Res, 1984 Dec, 155(2), 345 - 58
Contribution of alpha-D-galactopyranosyl end groups to attachment of highly and low metastatic murine fibrosarcoma cells to various substrates; Grimstad IA et al.; There are much greater numbers of cell surface terminal, non-reducing alpha-D-galactorpyranosyl groups in highly malignant (metastatic) cells than are found in low malignant cells derived from the same murine fibrosarcoma . We have examined the contribution of these residues to attachment of the cells to various collagens and to plastic . Removal of these carbohydrate groups with alpha-galactosidase or blocking them with lectins from Griffonia simplicifolia seeds or with anti-blood group B antiserum all dramatically inhibited the attachment of both the highly malignant and the low malignant cells . Following removal with the enzyme, the alpha-D-galactopyranosyl end groups were rapidly resynthesized . This resynthesis was inhibited by tunicamycin, an inhibitor of de novo glycoprotein synthesis . This antibiotic also impaired cell attachment and, when used in addition to treatment with alpha-galactosidase, it inhibited cell attachment more than did treatment with the enzyme alone . The effects of all treatments on cell attachment were greater for the highly malignant than for the low malignant cells . With the latter cells, inhibition by lectin was seen only in the absence of serum, whereas the adhesion of highly malignant cells was affected in both the presence and the absence of serum . On their surface membrane the highly malignant cells express much more than do the low malignant cells of a glycoprotein that cross-reacts immunologically with laminin . The basement membrane glycoprotein laminin promotes cell attachment to collagen, and both glycoproteins contain terminal, non-reducing alpha-D-galactopyranosyl groups . Attachment of cells is a requirement for the formation of a metastasis, and thus the laminin-like molecule and the alpha-D-galactopyranosyl end groups (whether on the laminin-related moiety or on other cell surface molecules) may both be important for expression of the most malignant phenotype.

J Hosp Infect, 1984 Dec, 5 Suppl A, 57 - 62
Competing risk factors associated with nosocomial infection in two university hospitals; Chavigny KH et al.; An historical cohort study of risk factors associated with nosocomial infection was conducted in two university hospitals on the East and West Coast of the USA . The purpose of the study was to estimate the relative risk ratios (RR) associated with antibiotic therapy, instrumentation, surgical operations and age with nosocomial infection, and to establish the hierarchical relationship of these factors to each other . A high risk cohort of long-staying patients (average length of stay = 30 days), was selected and each patient's chart was analysed retrospectively for infection occurrence and for risk factors . There was no significant difference between hospitals in rates of nosocomial infections, diagnostic categories and utilization of risk factors . Categorical linear regression analysis showed that a four factor model consisting of antibiotic therapy, instrumentation, surgical operations and age accounted for 95 per cent of the variation in nosocomial infection rates . Length of stay was treated as a co-dependent variable . Multivariable stratification analysis yielded aetiologic fractions of 63 per cent attributable to antibiotic therapy, 26 per cent to surgical operations, and 13 per cent to instrumentation . About half the antibiotic therapy was given on admission or at least 4 days before the first hospital-acquired infection . These data support careful assessment of prophylactic antibiotic therapy and infection control policies to reduce risk of nosocomial infection in university hospitals.

Antimicrob Agents Chemother, 1984 Dec, 26(6), 892 - 7
Stimulatory, permeabilizing, and toxic effects of amphotericin B on L cells; Brajtburg J et al.; High concentrations of amphotericin B (AmB) killed mouse L cells, but low concentrations increased plating efficiency and stimulated the incorporation of labeled precursors into DNA and RNA . Thus, there were two disparate effects of AmB on L cells, stimulatory and toxic, and they occurred in distinct dose-related stages . AmB also affected the permeability of L cells . In dose-response studies, increases in cell membrane permeability, measured as the loss of K+ ions, occurred along with the stimulation of {3H}uridine incorporation into RNA . In contrast, stimulation of {3H}thymidine incorporation into DNA was only observed in cells recuperating from AmB-induced permeability changes . When the K+ concentration in the medium was lowered to 0.5 from 4.5 mM, or when 1 mM ouabain was added to the cultures, cell killing was potentiated, but the stimulatory and permeabilizing effects of subtoxic concentrations of AmB were unaffected . Furthermore, etruscomycin, a polyene antibiotic without any permeabilizing effects, nevertheless induced an enhancement of plating efficiency and of incorporation of {3H}uridine into RNA and {3H}thymidine into DNA . Our results suggest that the dose-related stimulatory, permeabilizing, and toxic effects of AmB most probably have distinct mechanisms of action and may be independent of one another.

Boll Soc Ital Biol Sper, 1984 Nov 30, 60(11), 2143 - 8
{Evaluation of the effect of cloxacillin on human lymphocyte chromosomes through the study of karyotypic changes and sister chromatid exchanges}; Zavarise G et al.; The aim of this work was the evaluation of the possible mutagenic effect of an antibiotic, the Cloxacillin . Therefore the authors have performed the analysis of the chromosomal alterations and the study of the SCE (Sister Chromatid Exchanges) induced with the exposition of cultures of lymphocytes to different concentrations of this drug . The work reveals that Cloxacillin induces chromosomal alterations at high concentrations, while at concentrations similar to its therapeutic levels the drug does not seem to interfere with human DNA.

Biochim Biophys Acta, 1984 Nov 28, 802(2), 162 - 8
Evidence of different binding sites for nogalamycin in DNA revealed by association kinetics; Fox KR et al.; The kinetics of association between nogalamycin and DNA have been measured by stopped-flow spectrometry . With a naturally occurring DNA (calf thymus) the reaction profile requires not less than three exponentials for its complete description . By contrast, binding to poly(dA-dT) is fully described by two exponentials which correspond to the two faster components seen with the natural DNA, whereas binding to poly(dG-dC) is a single exponential process whose time constant is about the same as the slowest component measured with calf thymus DNA . In all cases the amplitude of each component in the decay varies considerably with polynucleotide concentration . The results are consistent with a model in which the antibiotic is only able to bind directly to regions of the DNA which are transiently perturbed, probably non-basepaired . As a result, the antibiotic interacts much faster with AT-rich rather than GC-rich DNA sequences, which may provide a basis for its apparent sequence selectivity.

Biochim Biophys Acta, 1984 Nov 22, 783(2), 166 - 70
The effects of paromomycin on the fidelity of translation in a yeast cell-free system; Tuite MF et al.; The effects of the aminoglycoside antibiotic paromomycin on the fidelity of translation of the synthetic template poly(U), and two natural mRNAs (rabbit globin mRNA and Brome Mosaic virus RNA), were examined in an mRNA-dependent cell-free system from the yeast Saccharomyces cerevisiae . At antibiotic concentrations that did not inhibit translation (100 microM) optimal mistranslation of all three templates was observed, with the effects declining at higher antibiotic concentrations . Synthesis of the opal termination read-through protein of rabbit beta-globin mRNA was induced by paromomycin, but only in lysates prepared from a {psi+} strain of yeast . The antibiotic did not induce detectable levels of either ochre or amber read-through, but did induce general misreading of Brome Mosaic virus RNA to the same degree in both {psi+} and {psi-} lysates . This misreading was enhanced by addition of the polyamine spermidine.

Schweiz Med Wochenschr, 1984 Nov 17, 114(46), 1651 - 5
{How bothersome is fiber bronchoscopy under local anesthesia?}; Langer T et al.; All the 79 (7.4%) complications of 1066 fiberoptic bronchoscopies performed under standardized topical anaesthesia in in- and outpatients were analyzed retrospectively . With the 4.9 mm bronchoscope the transnasal route was possible in all cases, and with the 6.0 mm bronchoscope in 92% . There were no deaths and no major complications, with the exception of one tension-pneumothorax, one pneumonia, one pulmonary edema and one 500 ml hemorrhage . The most frequent complications were minor hemorrhages (4.1%) which occurred mainly after biopsies and were rarely recognized by the patients . laryngospasms (1.5%) and bronchospasms (1.4%) . The rate of complications was higher in patients with a FEV1 of less than 60% predicted (p = 0.02) and in patients with a pO2 below 50 mm Hg (p = 0.06) . We recommend the administration of oxygen during fiberoptic bronchoscopy . Fever within 36 hours after bronchoscopy was observed in 12% and subsided without antibiotic therapy . In the light of these risks, patients should be informed prior to the procedure of the possible occurrence of shortness of breath, hemorrhage and fever.

Cancer, 1984 Nov 15, 54(10), 2109 - 21
Familial hemophagocytic lymphohistiocytosis (FHLH) in Israel . I . Description of 11 patients of Iranian-Iraqi origin and review of the literature; Stark B et al.; Eleven patients with familial hemophagocytic lymphohistiocytosis (FHLH) are described . They all belonged to four Jewish families of Iranian and Iraqi origin . Parental consanguinity was found in three families . The age of onset of disease ranged from 6 weeks to 36 months . All patients had fever, wasting, and enlargement of the liver and spleen . In addition, lymph-node enlargement and neurologic complications were common . The most consistent laboratory findings were pancytopenia, atypical lymphomonocytoid cells in the peripheral blood, abnormal liver function test results, and increased cerebrospinal fluid protein . The course was fatal in all patients . Nine of the 11 patients died within 2 weeks to 3 months of presentation, and 2 patients achieved temporary remissions but died of disease within 8 and 24 months, respectively . Response to antibiotic therapy or to the administration of corticosteroids and cytotoxic drugs was unimpressive . Pancytopenia complicated by sepsis or bleeding, hepatic failure, or encephalopathy were the terminal events . This report draws attention to the existence of FHLH in Jews of Iranian-Iraqi origin in whom parental consanguinity is very common.

Z Hautkr, 1984 Nov 15, 59(22), 1515 - 21
{Internal versus topical tetracycline therapy of acne}; Schwanitz HJ et al.; The study comprised 49 patients suffering from acne who were treated over a period averaging 4.7 +/- 1.2 months with tetracyclines administered either orally (1000 mg daily for 5 days, then 250 mg daily) or locally (2% alcoholic solution) . Randomization was carried out by means of random numbers . The percentage of pustules among the total acne efflorescences was chosen as clinical parameter for the efficacy of the antibiotic therapy . After treatment, both collectives showed the same significant decline of pustulation . The therapy was finally evaluated on a six-point scale both by the doctor and the patient . In total, there could not be detected any significant difference in the evaluation of local and oral medication.

Arkh Anat Gistol Embriol, 1984 Nov, 87(11), 66 - 72
{Features of the structure of the mesenteric and tracheobronchial lymph nodes in rat offspring after exposure to tetracycline}; Savitskaia TN; Ante- and postnatal development of anatomical structures and cells of lymphatic nodes has been studied in rat offspring subjected to tetracycline effect during placentation and organogenesis (the 8th-14th days) and during fetogenesis (the 15th-20th days) . Tetracycline injection during the 8th-14th days of embryogenesis results in certain disturbances of the nodular structure formations, inhibition of lympho- and plasmo-cytopoesis against the background of a sharp increase in number of basophilic granulocytes and tissue basophils . The antibiotic effect on the 15th-20th days of embryogenesis does not disturb the lymph node formation, but produces an increasing number of lymphocytes, plasmocytes, macrophages, eosinophilic granulocytes and tissue basophils in them.

Antibiotiki, 1984 Nov, 29(11), 851 - 5
{Antitoxic properties of pantothenic acid derivatives, precursors of coenzyme A biosynthesis, with regard to kanamycin}; Moiseenok AG et al.; The effect of calcium pantothenate (CPN)B 4'-phospho-CPN (PCP), pantetheine (PT) and calcium S-sulfopantetheine (SPN) on acute toxicity of kanamycin sulfate was studied on albino mice . The above derivatives of pantothenic acid except PT lowered the antibiotic toxicity . The coefficient of the antitoxic effect (LD50/ED50) of SPN and PCP was 1.3-1.4 times higher than that of CPN . The combined use of kanamycin (1/5 of the LD50) with CPN, PCP or PT (30 mg/kg bw was equivalent to CPN) for 15 days prevented the increase in the total content of CoA and in the content of the fraction of free CoA and the precursors of its biosynthesis participating in the reaction of N-acetylation in the liver and brain . The contents of these substances were within the normal during the whole experiment . A certain increase in the activity of pantothenate kinase in the liver cytosol due to the use of kanamycin was eliminated by the simultaneous use of PCP and PT . The vitamin-containing compounds PCP and SPN were recommended for the clinical trials as agents preventing complications of kanamycin therapy.

Acta Chir Belg, 1984 Nov-Dec, 84(6), 361 - 3
{Conservative treatment of a traumatic biliopleural fistula}; De Groof E et al.; Conservative management of a traumatic biliopleural fistula . A female patient, 13 years of age, developed a right-sided haemothorax after a stab wound in the right para-vertebral region . Pleural effusion reoccurred after thoracic drainage was stopped . Ten days after the injury, thoracic puncture enabled a diagnosis of biliopleural fistula to be made, confirmed by ERCP and CT-scan . The fistula closed after repeat thoracic drainage combined with prophylactic antibiotic therapy.

Eur J Cell Biol, 1984 Nov, 35(2), 189 - 99
Filipin as a cholesterol probe . I . Morphology of filipin-cholesterol interaction in lipid model systems; Beknke O et al.; We report some novel morphological observations on the interaction of the polyene antibiotic filipin (crude complex) with cholesterol, studied in non-cellular systems with replication, freeze-fracture, and negative stain techniques . Cholesterol crystals, lecithin liposomes containing 0 to 20 mole% of cholesterol, and liposomes containing 10 mole% of cholesterol and 5 to 40 mole% of sphingomyelin were incubated for varying lengths of time with filipin at different cholesterol: filipin molar ratios . The resulting filipin-induced lesions (FIL) were pleomorphic in all systems studied . In replicas of crystals, FIL appeared as ridges which were either straight, or curved into C- and S-shaped figures or closed circles . Negatively stained preparations showed FIL as white lines of the same configurations and in addition revealed a delicate veil attached to individual FIL . FIL, fused by their veils into clusters or large sheets ("holey sheets"), were shed from crystals . Incubation of liposomes for 1 h at cholesterol:filipin molar ratios of 4:1, 2:1, 1:1, and 1:5, demonstrated that cholesterol detection (i.e . formation of FIL) depend upon the ratio of cholesterol to filipin . At a 1:1 molar ratio FIL formed on liposomes containing 10 mole% cholesterol or more, but detectability increased to 5 mole% at the 1:5 ratio . Increasing the molar ratio of cholesterol:filipin to 2:1 and 4:1 decreased cholesterol detectability to between 10 and 20 mole% . Increasing concentrations of sphingomyelin decreased cholesterol detectability at the 1:1 cholesterol:filipin ratio; further, FIL in sphingomyelin-containing liposomes tended towards larger diameters . Filipin induced aggregation of liposomes and linked them together by holey sheets, providing evidence for filipin-induced extraction of cholesterol from liposomes . Taken together our morphological observations on filipin-cholesterol interaction in non-cellular systems raise pertinent questions as to the feasibility of filipin as a cholesterol probe in cellular systems.

J Anim Sci, 1984 Nov, 59(5), 1125 - 8
Efficacy of nosiheptide as a growth promotant for growing-finishing swine--a cooperative study; Cromwell GL et al.; A cooperative study involving 296 pigs was conducted at two experiment stations and at a commercial research farm to evaluate the efficacy of nosiheptide as a growth promotant for growing-finishing swine . At each station, five or six replicate pens of four or five pigs/pen were fed a fortified, corn-soybean meal basal diet with 0, 5.5, 11 or 22 ppm nosiheptide . Initial and final weights averaged 11 and 92 kg, respectively . Daily gain increased quadratically (623, 664, 669, 678 g/d; P less than .03) and feed/gain decreased quadratically (3.35, 3.24, 3.24, 3.28; P less than .02) with increasing level of nosiheptide . Breakpoint analysis indicated that gain plateaued at 6.8 ppm and feed/gain at 5.5 ppm of nosiheptide . Averaged across all levels of nosiheptide, gain and feed/gain during the growing phase (11 to 52 kg body weight) were improved by 13.1 and 7.6%, respectively, by feeding the antibiotic . For the entire growing-finishing period, gain was improved by 5.3% and feed/gain by 2.9% in pigs fed nosiheptide . Although there were large differences in gain and feed/gain, the responses to dietary treatments were similar among the three stations . The results indicate that nosiheptide is an effective growth-promoting agent for growing-finishing swine.

J Antibiot (Tokyo), 1984 Nov, 37(11), 1344 - 56
Structure and properties of major largomycin FII chromophore components; Gonda SK et al.; Largomycin FII, a protein antitumor antibiotic of molecular weight 29,300 daltons, contains a chromophore that is separable under mild denaturing conditions . The chromophore complex was found to be considerably less stable than the holoprotein towards light and heat, suggesting a protective effect of the protein on the chromophore . Separation of the chromophore into several components was achieved using high performance liquid chromatography, and the biological activity of the isolated components was determined . Data gathered from UV, IR, proton and carbon NMR, and fast atom bombardment mass spectrometry indicated that all the chromophore components belong to the pluramycin class of antitumor agents . Pluramycin A and deacetylpluramycin A were found to be the two major components.

Arch Surg, 1984 Nov, 119(11), 1325 - 8
Complications of renal dialysis access procedures; Connolly JE et al.; The complications of 2,179 dialysis access procedures of various types have been reviewed in an effort to determine their possible prevention and management . Scribner arteriovenous shunts or central venous catheters were preferred for temporary dialysis . Infection was a common complication of central venous catheters, but responded well to removal of the catheter . Brescia-Cimino fistulae were preferred for long-term dialysis, but were often not possible because of inadequate veins or the need for relatively urgent hemodialysis . The most useful secondary shunt was the straight forearm synthetic polytetrafluoroethylene (PTFE) graft whose most common complication was thrombosis due to intimal hyperplasia at the venous anastomosis . In most cases, this complication could be corrected by patch grafting or by extension bypass . Infection was infrequent with PTFE shunts and, when localized, was sometimes successfully treated by drainage, antibiotic therapy, and topical povidone-iodine . The principal complications of long-term peritoneal dialysis were peritonitis and tunnel infection that responded to antibiotic therapy and/or removal of the catheter . Compulsive care in access insertion and meticulous management during dialysis has permitted very satisfactory long-term hemodialysis and peritoneal dialysis.

Am J Clin Pathol, 1984 Nov, 82(5), 611 - 5
Rhinosporidiosis . A report of two cases from Arkansas; Jimenez JF et al.; Two human native cases of ocular-conjunctival rhinosporidiosis from Arkansas are believed to be the first documented reports in this part of the country . The common mode of infection was accidental injury to the eye by possible contaminated soil-dust . The appearance of the polypoid growth was relatively fast, 6-16 days, and unresponsive to topical antibiotic and steroid treatment . Surgical excision, with one recurrence in one case, was the elective treatment . Both patients are asymptomatic 10-12 months after treatment, respectively, with no evidence of other recurrence, dissemination, or major complications . From 1939 to September, 1983, only nine cases of conjunctival rhinosporidiosis were reported in the United States.

Clin Orthop, 1984 Nov, (190), 266 - 72
The influence of etiology on the results of coccygectomy; Bayne O et al.; The results of coccygectomy for coccygodynia seem not to have been correlated with etiologic factors and were investigated in 48 cases (10 men and 38 women) with an average follow-up period of seven years . The following four etiologic groups were designated: I, direct trauma; II, spontaneous in origin; III, coccygodynia associated with spinal surgery; and IV, postpartum . Groups I and IV had a 75% recovery rate from pain and Group II had a 58% recovery rate . No satisfactory results were obtained in Group III . The incidence of infection was 16.6% . Few satisfactory results were obtained in cases of deep infection . While this operation is effective in many cases, it is seldom successful for pain associated with lumbar disc disease requiring lumbar laminectomy and spine fusion . Prophylactic antibiotic therapy is clearly indicated.

Radiology, 1984 Nov, 153(2), 357 - 61
Aortic root abscess resulting from endocarditis: spectrum of angiographic findings; Miller SW et al.; Abscesses in the aortic root are a serious complication of infective endocarditis and require accurate diagnosis for antibiotic and surgical management . Nineteen cases of endocarditis of a native valve or prosthetic valve and adjacent abscess cavities were identified with angiography . Of 6 patients with endocarditis of a native valve, 5 had bicuspid aortic valves and all had severe aortic regurgitation . Of 13 patients with endocarditis of a prosthetic aortic valve, all had paravalvular regurgitation . Abscesses in the aortic root were saccular, ranged from 1 to 3 cm in diameter, and, depending on sinus of origin, extended beneath the main and right pulmonary arteries or into the interventricular septum or mitral anulus . Fistulas were detected into the mitral anulus in 8 patients, and into the right ventricle in 3 patients . No complications from the catheterization were recorded during the 48-hour follow-up.

Gastroenterology, 1984 Nov, 87(5), 1091 - 103
Structural features of and cholesterol distribution in M-cell membranes in guinea pig, rat, and mouse Peyer's patches; Madara JL et al.; Evidence suggests that M cells, which are antigen-sampling epithelial cells that overlie the domes of Peyer's patches, have an apical plasma membrane that differs from that of absorptive cells . We examined the structural features of rat, mouse, and guinea pig M-cell apical membranes and compared them with those of dome and villus absorptive cell apical membranes using electron microscopy of thin sections and freeze-fracture replicas . We also determined the distribution of morphologically detectable cholesterol in M-cell plasma and intracellular membranes in dome epithelium exposed to the polyene antibiotic, filipin . The areal density of P-face intramembrane particles was significantly less on M-cell microvilli than on microvilli of dome absorptive cells and villus absorptive cells . Areal densities of E-face intramembrane particles were similar on M-cell and absorptive-cell microvilli . M-cell apical plasma membranes were rich in cholesterol, displaying numerous filipin-induced membrane lesions in thin sections and freeze-fracture replicas . In contrast, apical membrane endocytic pits and coated vesicles in M cells failed to show filipin-induced membrane lesions . These findings suggest that, compared with the apical membranes of absorptive cells, those of M cells have a low protein to lipid ratio and an abundance of morphologically detectable cholesterol except in domains involved in endocytosis . Additionally, a subpopulation of dome epithelial cells displayed distinctive tight junctions with high strand counts and unusual depth . Although the cell type associated with these modified tight junctions could not be identified with certainty, their interspecies frequency paralleled the interspecies frequency of M cells in dome epithelium . These expanded tight junctions may result from physical tension caused by epithelial shape changes induced by intraepithelial lymphoid trafficking or, alternatively, may help buttress M cells that have attenuated cytoplasmic processes due to the presence of central hollows.

J Hand Surg {Am}, 1984 Nov, 9(6), 894 - 8
A functional treatment method for interphalangeal pyogenic arthritis; Wittels NP et al.; A treatment plan for pyogenic arthritis has been devised in which the accessory collateral ligaments are resected through radial and ulnar midaxial incisions . The surgical wound is debrided and copiously irrigated with an antibiotic solution, and intravenous antibiotics are instituted before operation and continued after operation . Physical therapy is begun within 24 hours of surgery and includes active range of motion (ROM) of all joints, dynamic splinting, and hand therapy to ensure both full flexion and extension . Forty patients were treated with this method within a 6-year period . Of five interphalangeal (IP) joints of the thumb, four regained 0 degree to 60 degrees full ROM and one gained 15 degrees to 65 degrees limited ROM . Of the two distal IP joints, one regained full ROM and the other became fused . Among the 33 proximal IP joints, 13 regained full ROM of 110 degrees and 13 regained limited ROM . Good functional results were obtained with this treatment plan in lieu of amputation, which previously was the most likely treatment.

Am Heart J, 1984 Nov, 108(5), 1326 - 34
Gonococcal endocarditis: a case series demonstrating modern presentation of an old disease; Fernandez GC et al.; Gonococcal endocarditis appeared with striking frequency in the preantibiotic era compared with its surprising rarity today . We present a series of four episodes of gonococcal endocarditis, which presented to our institution in the last 2 years, after no cases in the previous decade . Three episodes involved the aortic valve and required emergency aortic valve replacement . One episode involved the tricuspid valve and was successfully cured with antibiotic infusion alone . Combining our four patients with the available 25 well-documented gonococcal endocarditis cases reported in the English medical literature during the antibiotic era, we demonstrated that the disease incidence may be increasing, that infections more often involve left-sided cardiac structures (particularly the aortic valve), and that the association with a quotidian fever curve, rash and arthritis, and overt gonococcal infection is less common than previously reported . These patients frequently present with fulminant and dramatic valvular insufficiency without immediately positive blood cultures and complete echocardiographic evaluation seems to provide a valuable aid in making a presumptive diagnosis of endocarditis and directing appropriate clinical management.

Ann Intern Med, 1984 Nov, 101(5), 683 - 91
The pregnant surgical patient: medical evaluation and management; Barron WM; Nonobstetric disease requiring surgery may complicate pregnancy and jeopardize maternal and fetal well-being . Surgery may be safely done if the physician is aware of anatomic and physiologic alterations during gestation that necessitate an altered approach to diagnosis and management . Fetal exposure to all diagnostic and therapeutic agents should be minimized, particularly during organogenesis . However, the risk to the fetus of diagnostic irradiation is justifiable when information essential to maternal health is likely to be obtained . Furthermore, the broad range of available antibiotic, analgesic, and anesthetic agents provide the physician with options for treatment that have an acceptable degree of risk to fetal health . Anesthesia and surgery are tolerated considerably better by the fetus than is maternal hypotension, hypoxia, or sepsis . When an operative procedure is urgently or emergently indicated, pregnancy should not delay timely intervention.

EMBO J, 1984 Nov, 3(11), 2575 - 80
Hyper-accurate ribosomes inhibit growth; Ruusala T et al.; We have compared both in vivo and in vitro translation by ribosomes from wild-type bacteria with those from streptomycin-resistant (SmR), streptomycin-dependent (SmD) and streptomycin-pseudo-dependent (SmP) mutants . The three mutant bacteria translate more accurately and more slowly in the absence of streptomycin (Sm) than do wild-type bacteria . In particular, the SmP bacteria grow at roughly half the rate of the wild-type in the absence of Sm . The antibiotic stimulates both the growth rate and the translation rate of SmP bacteria by approximately 2-fold, but it simultaneously increases the nonsense suppression rate quite dramatically . Kinetic experiments in vitro show that the greater accuracy and slower translation rates of mutant ribosomes compared with wild-type ribosomes are associated with much more rigorous proofreading activities of SmR, SmD and SmP ribosomes . Sm reduces the proofreading flows of the mutant ribosomes and stimulates their elongation rates . The data suggest that these excessively accurate ribosomes are kinetically less efficient than wild-type ribosomes, and that this inhibits mutant growth rates . The stimulation of the growth of the mutants by Sm results from the enhanced translational efficiency due to the loss of proofreading, which more than offsets the loss of accuracy caused by the antibiotic.

J Bacteriol, 1984 Nov, 160(2), 533 - 40
Mutants of Aspergillus nidulans blocked at an early stage of sporulation secrete an unusual metabolite; Butnick NZ et al.; Mutants of Aspergillus nidulans defective in conidiation (asexual sporulation) can be classified according to whether they are blocked before or after induction of conidiation . Mutants blocked before induction (preinduction mutants) appear to be unable to respond to the inducing stimulus and thus are defective in one of the earliest events in the sporulation process . Three preinduction mutants have been isolated and characterized . Each was found to exhibit the same pleiotropic phenotype: they also were defective in sexual sporulation and secreted a set of phenolic metabolites at a level much higher than did wild type or mutants blocked at later stages of conidiation . One of the metabolites has been identified as the antibiotic diorcinal (3,3'-dihydroxy-5,5'-dimethyldiphenyl ether) which is known to be involved in the synthesis of certain farnesyl phenols of unknown function . These results suggest that preinduction mutants are blocked in a phenolic metabolic pathway, one or more product of which participates in the initiation of sporulation.

Clin Rev Allergy, 1984 Nov, 2(4), 319 - 28
Etiologic factors in the development of chronic middle ear effusions; Kraemer MJ et al.; Many factors increase the risk for CMEE in children . We believe the most important include recurrent purulent otitis media, chronic nasal congestion, atopy, and household cigarette smoke exposure . The risk of each of these in causing middle ear disease increases with the chronicity of the exposure . The risk may be additive, with a combination of these factors . CMEE undoubtedly develops through several mechanisms . It is important to look for specific risk factors, as their identification may afford potential approaches toward the prevention of recurrences . Theories such as prophylactic antibiotic administration, pneumococcal vaccination, pharmacologic therapy with antihistamines, decongestants and/or steroids, immunotherapy, and the avoidance of household irritants may be selectively beneficial for the appropriate individual . In an attempt to facilitate strategies to prevent acute middle ear disease as well as recurrent and chronic effusions, further understanding of the etiology, pathogenesis, and risk factors is prerequisite . Additional controlled studies in all of these areas are essential so that we may expand our knowledge base and offer more definitive recommendations to our patients and their families.

Tsitologiia, 1984 Nov, 26(11), 1267 - 72
{Cytophotometric study of the granules formed in frog erythrocytes incubated in solutions of acridine orange, chloroquine and daunorubicin}; Veselkina MN et al.; Granules arising in the cytoplasm of Rana temporaria erythrocytes incubated in either solution containing acridine orange, chloroquine or antibiotic daunorubicine were studied cytophotometrically . The stuff concentrations in the granules were estimated under various conditions of incubation . The stuff concentrations in the granules appeared to be 1000-fold higher than in the incubation solutions . The average concentration in the granules did not depend on either the initial concentration of the stuff solution or the incubation time . The stuff concentration in the granules decreases with the increase of the granule size . Mechanisms of cation-acid segregation and accumulation by living cell are discussed.

Proc Soc Exp Biol Med, 1984 Nov, 177(2), 247 - 52
Folate deficiency and pancreatic acinar cell function; Elseweidy M et al.; The present study was designed to determine the effect of folate deficiency on pancreatic acinar cell function . In the first series of experiments, three groups of rats were fed ad libitum regular rat feed, folate-deficient diet, or an equivalent amount of folate-sufficient diet . In the second series of experiments, rats were either fed ad libitum or rendered folate deficient by a purified folate-deficient diet; half of the folate-deficient group was replenished with oral folate . Body weight, pancreatic weight, DNA {methyl-14C}thymidine incorporation into DNA, RNA, {8-14C}adenine incorporation into RNA, protein content, synthesis of proteins, amylase content, and basal and bethanechol-stimulated amylase secretion were determined . The parameters were the same in the rats fed a folate-sufficient diet as in those fed a regular rat feed . Feeding a folate-deficient diet resulted in impaired DNA synthesis as evidenced by diminished incorporation of {methyl-14C}thymidine into DNA . There was no change in secretion of amylase . Similar results were obtained in the second series of experiments . These studies indicate that folate deficiency (rather than antibiotic content of the diet) impaired pancreatic function . Folate deficiency may therefore contribute to pancreatic injury in malnutrition and alcoholism.

J Foot Surg, 1984 Nov-Dec, 23(6), 445 - 50
Crush and avulsion injuries of the foot: their evaluation and management; Graziano TA et al.; It is difficult to assess the damage resulting from crush or avulsion injuries so they may be treated adequately . The authors present a systematic approach to evaluating tissue involved in foot trauma . They also discuss antibiotic and tetanus prophylaxis and a technique of bacterial quantification that is helpful in determining the advisability of primary or delayed wound closure.

Ann Allergy, 1984 Nov, 53(5), 370 - 8, 394
Otitis media with effusion in childhood; Marshall SG et al.; OM and OME are common disorders of childhood . Middle ear disease is related to anatomic abnormalities, prior episodes of AOM, chronic rhinitis, allergy, age, sex, race, season, perinatal factors, viral infections, and irritant exposure . ET dysfunction plays an important role in OME, as does the presence of bacteria or bacterial products in the middle ear . Viral infection, nasal allergy, previous episodes of OM and primary mucosal disease all may contribute to this chronic disorder . Diagnostic evaluation involves an appropriate personal and environmental history, a physical examination, pneumatic otoscopy, tympanometry, pure tone audiometry, and (if indicated) allergic and immunologic evaluation . Treatment may include environmental control, antibiotic therapy, decongestants and/or antihistamines, topical corticosteroids, and possibly immunization or allergic immunotherapy (hyposensitization) . In order to facilitate strategies to prevent acute and recurrent OM as well as chronic effusion, further knowledge regarding the etiology, pathogenesis, and risk factors is essential . Well designed, controlled studies are imperative to provide further understanding and more effective treatment of this common, chronic and often very frustrating medical problem.

Mol Cell Biol, 1984 Nov, 4(11), 2549 - 52
Efficient transfer of cloned DNA into human diploid cells: protoplast fusion in suspension; Litzkas P et al.; A method for fusion of protoplasts bearing amplified plasmids and human diploid fibroblasts or other cell types in suspension is described . Transient expression of plasmid-encoded proteins occurs in up to 50% of the human cells, as demonstrated for simian virus 40 T antigen by immunofluorescence and the Escherichia coli xanthine-guanine phosphoribosyl transferase by autoradiography . In contrast, frequencies of stable transformants were similar to those obtained by the CaPO4 coprecipitation technique . However, experiments with both methods involving the recombinant pRSVneo (in which the Rous sarcoma virus long terminal repeat regulates expression of the antibiotic-inactivating aminoglycoside phosphotransferase) revealed a much higher frequency of colonies in G418 selective medium with constructions in which the early region of simian virus 40 DNA was present as well . We propose a role for the simian virus 40 T antigen in enhancing stable transformation in this system.

Mol Cell Biol, 1984 Nov, 4(11), 2381 - 8
Asparagine-linked glycosylation in Saccharomyces cerevisiae: genetic analysis of an early step; Barnes G et al.; Asparagine-linked glycosylation is a form of covalent modification that distinguishes proteins that are either membrane bound or are in cellular compartments topologically outside of the cell from those proteins that remain soluble in the cytoplasm . This type of glycosylation occurs stepwise, with core oligosaccharide added in the endoplasmic reticulum and subsequent modifications occurring in the golgi . We used tunicamycin, an inhibitor of one of the earliest steps in the synthesis of N-linked oligosaccharide, to select for mutants that are resistant to this antibiotic . Genetic, biochemical, and physiological experiments led to the following conclusions . The synthesis of N-linked oligosaccharide is an essential function in cells . In contrast to mammalian cells, yeast cells do not transport tunicamycin by a glucosamine transport function . We identified a gene, ALG7, that is probably the structural gene for UDP-N-acetylglucosamine-1-P transferase, the enzyme inhibited by tunicamycin . Dominant mutations in this gene result in increased activity of the transferase and loss of the ability of the cell to sporulate . In addition, we identified another gene, TUN1, in which recessive mutations result in resistance to tunicamycin . The ALG7 and TUN1 genes both map on chromosome VII.

J Antibiot (Tokyo), 1984 Nov, 37(11), 1370 - 5
Control of ammonium ion level for efficient nanaomycin production; Tanaka Y et al.; The addition of a small amount of NH4+ to a complex medium increased nanaomycin production by Streptomyces rosa subsp . notoensis OS-3966 . The best NH4+ donor for nanaomycin production was NH4+-saturated natural zeolite, with which the maximum titer of nanaomycin E was 760 micrograms/ml, about four fold higher than the control titer . In contrast, lowering NH4+ levels by adding NH4+-trapping agents such as untreated natural zeolite reduced antibiotic production.

J Virol, 1984 Nov, 52(2), 370 - 6
Herpes simplex virus cloned DNA fragments induce coumermycin A1 resistance in Escherichia coli; Pearson RE et al.; We have taken a new approach to identify and fine map previously undescribed herpes simplex virus (HSV) functions . In experiments described in this report the antibiotic coumermycin A1 was used to select two HSV type 1 BamHI fragments cloned in pBR322 that confer partial resistance to drug-susceptible Escherichia coli . The genes encoding these HSV functions have been designated cour-1 and cour-2 and have been fine mapped to the HSV sequences . HSV-cour1 is located at the left end of BamHI-F near HSV type 1 genomic map coordinate 0.645 . cour-2 maps to BamHI-M', which is a 159-base-pair internal component of the alpha ICP4-coding sequence located in the reiterated sequences of the S component . In pBR322 both inserts apparently rely on the tet promoter for expression . Additionally, cour-2 functions when present as a BamHI insert in pUC7 . The analysis of cour-2 "maxi" cell proteins reveals the presence of proteins produced by the fusion of HSV-1 BamHI-M' sequences and the sequences of the vector genes, i.e., the major tet product for pBR322 and the modified beta-galactosidase for pUC7 . These data suggest that the development of bacterial assays for fusion products of eucaryotic DNA open reading frames in plasmid vectors may be a useful technique for initiating gene function studies.

J Clin Oncol, 1984 Nov, 2(11), 1270 - 6
Sudden death in cancer patients receiving lithium; Lyman GH et al.; Lithium carbonate may attenuate the incidence and severity of infection associated with cancer chemotherapy but does not appear to improve patient survival . Of 100 patients with small-cell lung cancer receiving an identical regimen of cyclophosphamide, doxorubicin, and vincristine, 40 were assigned to treatment with lithium concurrently . To date, 60 patients have died, including 14 who died suddenly of apparent cardiovascular causes without evident progression of neoplastic disease or concurrent illness . Thirteen of the 14 sudden deaths were among 50 patients with clinical or electrocardiographic evidence of cardiovascular abnormalities before study entry . Among patients with pretreatment cardiovascular abnormalities, lithium administration was associated with a greater risk of sudden death and shorter survival . A strong interaction for risk of death was evident between lithium treatment and the use of bronchodilators . In multivariate analysis, the major predictors of patient survival were the quality of tumor response and treatment with lithium with or without bronchodilators . Lithium treatment is a major risk factor for sudden death in cancer patients with pretreatment cardiovascular changes receiving combination chemotherapy including an anthracycline antibiotic.

Am J Vet Res, 1984 Nov, 45(11), 2243 - 6
Effect of dihydrostreptomycin or oxytetracycline on reproductive capacity of bulls; Abbitt B et al.; Young beef bulls (n = 27) were used in a trial to study the effect of dihydrostreptomycin sulfate (DHS) or oxytetracycline (OTC) hydrochloride on spermatogenesis, epididymal sperm maturation, and freezability of sperm . Nine of the bulls were given a 22 mg/kg dose of DHS twice, 12 hours between doses . Nine other bulls were treated with OTC--1 dose of 26.4 mg/kg of body weight, and then 6 more doses each of 17.6 mg/kg, ca 12 hours between doses . The remaining 9 bulls were nontreated controls . The treatment regimens with the 2 antibiotics were without effect on spermatogenesis . These treatments also were without effect on seminal pH, ejaculate volume, percentage of motile spermatozoa, rate of spermatozoal motility, or concentration of spermatozoa in ejaculates harvested on day 3 or 7 of the study (day 0 = 1st day of treatment) . There was a treatment-by-day effect on spermatozoal concentration; the number of sperm per milliliter was markedly increased on day 3 for OTC-treated bulls . The increased spermatozoal concentration in the OTC-treated group was associated with an influence of the antibiotic on ejaculation . All bulls given this antibiotic ejaculated without palpable penile engorgement or erection on day 3 . On day 7 the rate of spermatozoal motility was increased in the 2 treatment groups compared with the rate in the control bulls . Also on day 7, the percentage of motile spermatozoa was greater in the OTC-treated bulls than in the control or DHS-treated bulls.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Med, 1984 Oct 30, 77(4D), 28 - 33
Oral candidiasis; Dreizen S; Candidiasis is, by far, the most common mycotic infection of the human oral cavity . The usually manifested clinical expression of oral candidiasis at all ages from the newborn to the elderly is thrush . Other forms that affect the mouth include acute atrophic candidiasis associated with oral antibiotic therapy, chronic atrophic candidiasis attributable to the wearing of full upper dentures, candidal cheilosis ascribable to perleche or decreased vertical dimension in the lower third of the face, chronic mucocutaneous candidiasis emanating from a T-lymphocyte deficiency, and candidal leukoplakia . Extensive use of antibiotics and immunosuppressive drugs have greatly increased the number of Candida-induced oral infections . Patients debilitated by irradiation, cancer chemotherapy, organ transplants, diabetes mellitus, and defects in cell-mediated immunity are particularly vulnerable . Fortunately, the vast majority of cases of oral candidiasis are not life-threatening and readily respond to appropriately administered anticandida agents . It must always be remembered, however, that the organism has the capacity to produce fulminating fatal infection by hematogenous dissemination from seemingly innocuous oral infections that serve as a portal of entry to the systemic circulation . Consequently, all oral candidal infections in compromised patients must be treated vigorously and effectively.

Biochem Biophys Res Commun, 1984 Oct 30, 124(2), 388 - 92
Enhancement of S1 nuclease-susceptibility of negatively superhelical DNA by netropsin; Shishido K et al.; It was evidenced that the antibiotic netropsin enhances the single-strand-specific nuclease S1-susceptibility of negatively superhelical DNA . In contrast, an intercalating drug inhibited S1 action on the superhelical DNA . Negatively superhelical DNA is known to possess several (or a number of) unbasepaired sites sensitive to S1 cleavage . S1 cleaves generally the DNA once at these sites to result in production of the full-length linear form . However netropsin-bound DNA had a tendency to be cleaved by S1 simultaneously at plural sites producing several species of linear DNAs smaller than full-length size.

Am J Med, 1984 Oct 30, 77(4D), 20 - 7
Systemic candidiasis in cancer patients; Maksymiuk AW et al.; Two hundred thirty-five fungal infections occurred in patients with malignant diseases over a four-year period . One hundred eighty-eight were due to Candida species and Torulopsis glabrata and are reviewed herein . The frequency was highest in patients with acute leukemia (11.9 per 100 registrations) with a frequency of 0.8 per 100 registrations in all cancer patients at this institution . Three or more predisposing factors were present in more than 50 percent of the cases; antecedent myelosuppression, chemotherapy, and antibiotic therapy were most common . Blood cultures were positive in only 35 percent of patients with disseminated candidiasis . Twenty-nine of 55 patients (53 percent) had candidemia without identifiable organ infection recovered . Eleven were given no systemic antifungal therapy and recurrence of infection was documented in two patients . Only six (4.5 percent) of 133 patients with proved deep organ infections recovered . Respiratory failure was the clinical cause of death in 62 percent of patients . Clinical features, cultures, and serologic tests were usually of no assistance in establishing the diagnosis early in the course of the infection.

Biochim Biophys Acta, 1984 Oct 26, 767(1), 130 - 7
An investigation on the effect of oligomycin on state-4 respiration in isolated rat-liver mitochondria; Masini A et al.; The inhibitory action of oligomycin on State-4 respiration in rat-liver mitochondria has been investigated in detail with regard to the extent, mode and characteristics of the inhibition . The possibility that this effect may be due either to some damage of the mitochondrial preparation used or to the presence of heavy contaminations by microsomes has been excluded . It has been found that the concentration of specific binding sites is the same in State 4 as in State 3 . The extent of the inhibition appears to be related to the ADP concentration, rather than to ATP/ADP ratios . The inhibition of this antibiotic on State-4 respiration does not depend on the experimental conditions used (i.e., choice of substrates or composition of the reaction medium) . In agreement with these observations, it has been found that the membrane potential of State 4 is significantly increased when oligomycin is added . All these results provide further evidence to the conclusion that a large portion of State-4 respiration is linked to phosphorylation.

N Engl J Med, 1984 Oct 25, 311(17), 1065 - 70
Risk of infection after penetrating abdominal trauma; Nichols RL et al.; To identify the risk factors for the development of postoperative septic complications in patients with intestinal perforation after abdominal trauma, and to compare the efficacies of single-drug and dual-drug prophylactic antibiotic therapy, we studied 145 patients who presented with abdominal trauma and intestinal perforation at two hospitals between July 1979 and June 1982 . Logistic-regression analysis showed that a higher risk of infection (P less than 0.05) was associated with increased age, injury to the left colon necessitating colostomy, a larger number of units of blood or blood products administered at surgery, and a larger number of injured organs . The presence of shock on arrival, which was found to increase the risk of infection when this factor was analyzed individually, did not add predictive power . Patients with postoperative sepsis were hospitalized significantly longer than were patients without infection (13.8 vs . 7.7 days, P less than 0.0001) . Both treatment regimens--cefoxitin given alone and clindamycin and gentamicin given together--resulted in similar infection rates, drug toxicity, duration of hospitalization, and costs.

N Z Med J, 1984 Oct 24, 97(766), 724 - 7
Asthma management within North Canterbury general practice; Simpson JB et al.; During 1980/81 a primary medical care survey comprising 4629 patient visits to North Canterbury general practitioner surgeries was undertaken . Given the current concern about asthma management information concerning asthma consultations was extracted from the survey . The diagnostic procedures undertaken, therapeutic services provided and follow-up arrangements are outlined for 96 patients with a primary diagnosis of asthma . Pharmaceuticals prescribed to 116 patients with either a primary or secondary diagnosis of asthma are described . Of those patients requiring medication 52% received only one item . Beta 2-agonists were the most commonly used antiasthmatic and were prescribed to 78% of the 116 patients . Theophylline was prescribed to 41% of cases, beclomethasone to 28%, oral corticosteroids to 22%, sodium cromoglycate to 12% and an antibiotic to 10% of cases . These results reflect pharmaceuticals prescribed at one point in time of on-going care.

Am J Med, 1984 Oct 19, 77(4C), 84 - 8
Clinical adverse effects during ceftriaxone therapy; Moskovitz BL; The clinical safety of ceftriaxone administered at various doses for time periods ranging from a single injection to up to six weeks was evaluated in 2,640 patients treated in 153 individual studies . The incidence of clinical adverse effects was greatest for gastrointestinal (3.45 percent), hypersensitivity (2.99 percent), and local (1.86 percent) reactions . When the pediatric population was analyzed separately, the incidence of gastrointestinal and hypersensitivity reactions was 5.63 and 3.3 percent, respectively; all other reactions occurred in fewer than 1 percent of patients . The frequency of adverse effects for the once-daily and twice-daily dosing regimens was comparable, except for a statistically significant increase in local reactions when ceftriaxone was administered twice daily . When ceftriaxone was compared directly with other antibiotic regimens, the incidence of clinical adverse effects was similar . Ceftriaxone appears to be safe and well tolerated from a clinical standpoint.

Am J Med, 1984 Oct 19, 77(4C), 50 - 3
Ceftriaxone therapy of meningitis and serious infections; Steele RW; Thirty pediatric and young adult patients with bacterial meningitis were treated with ceftriaxone or "standard therapy" in a comparative trial; 41 other patients with severe bacterial infections were treated with ceftriaxone in an open protocol . Meningitis and brain abscesses were treated successfully with 50 mg/kg of ceftriaxone every 12 hours . In children, other infections were treated with 25 to 37.5 mg/kg of ceftriaxone every 12 hours . Young adults with pneumonia received 1 g of the antibiotic every 12 hours, whereas those with soft tissue infections were treated every 24 hours . All patients responded to therapy, and in all but one was the infectious process sterilized . No significant toxicity was observed . Ceftriaxone appears to be an excellent single agent for the treatment of most severe bacterial infections in pediatric and young adult patients and need not be administered more frequently than once every 12 hours.

Am J Med, 1984 Oct 19, 77(4C), 33 - 6
Diffusibility of the newer cephalosporins into human interstitial fluids; Tan JS et al.; A skin window technique was used to investigate the ability of three of the newer cephalosporins, moxalactam, cefoperazone, and ceftriaxone, to enter the interstitial fluid of normal, healthy volunteers . Intravenous and intramuscular routes of delivery were compared . The method of delivery did not greatly affect diffusibility with moxalactam and ceftriaxone . Intravenous infusion resulted in greater diffusibility with cefoperazone than did intramuscular injection . Cefoperazone demonstrated the lowest diffusibility of the three test drugs . Ceftriaxone, administered at one-half the dose of cefoperazone and moxalactam, demonstrated the greatest ability to diffuse into interstitial fluid despite its high level of binding to plasma protein . The better diffusibility of ceftriaxone may be explained by a persistently high concentration gradient provided by its long serum half-life . Overall, the results support the concept of the concentration gradient as an important determinant of antibiotic activity.

Nature, 1984 Oct 11-17, 311(5986), 575 - 7
Photoreceptor-specific degeneration caused by tunicamycin; Fliesler SJ et al.; The antibiotic tunicamycin inhibits the biosynthesis of N-acetylglucosaminylpyrophosphoryl polyisoprenol, a key intermediate in the formation of the asparagine-linked oligosaccharides of glycoproteins . The effects of tunicamycin have been studied in various biological systems, primarily with the aim of elucidating the role of the carbohydrate moieties in the cellular function of glycoproteins . Rhodopsin, the visual pigment of retinal rod photoreceptor cells, is a membrane glycoprotein which consists of a single polypeptide chain (opsin) to which a chromophoric prosthetic group (II-cis-retinaldehyde) and two asparagine-linked oligosaccharide chains are covalently attached . The glycosylation of opsin can be blocked with tunicamycin in vitro in conditions where polypeptide synthesis is only slightly decreased . We have reported that tunicamycin can disrupt the normal assembly of rod outer segment membranes in vitro without significantly inhibiting the biosynthesis or intracellular transport of opsin . Here we report that intraocular injection of tunicamycin produces a photoreceptor-specific degeneration characterized by progressive shortening of rod outer segment, decreased membrane assembly, and eventual photoreceptor cell death.

Biochim Biophys Acta, 1984 Oct 3, 776(2), 317 - 29
Amphotericin and model membranes . The effect of amphotericin B on cholesterol-containing systems as viewed by 2H-NMR; Dufourc EJ et al.; The interactions between amphotericin B and sterol-containing model membranes were monitored by 2H-NMR of deuterium-labelled dimyristoylphosphatidylcholine (DMPC), cholesterol and epicholesterol . The addition of amphotericin B to a cholesterol/DMPC (3:7) system was perceived differently by the lipid, depending upon the depth in the bilayer: no structural change was manifest in the acyl chain region associated with the plateau in molecular ordering (C4'), whereas the lipid clearly senses two environments near the center of the bilayer (C13', C14') . The amount as well as the ordering properties of the more ordered antibiotic-induced component, sensed at C14', increased with decreasing temperature . The structural parameters of deuterium-labelled cholesterol in cholesterol/DMPC mixtures were unchanged upon addition of amphotericin B, regardless of the bilayer depth . Upon addition of amphotericin B, the lipid T1 values are unchanged, whereas the T2 values are reduced by a factor of 2 . The minimum in T1 observed for cholesterol in DMPC at 32-35 degrees C was shifted towards 38-40 degrees C in the presence of amphotericin B . Epicholesterol-containing dispersions of DMPC had properties similar to those of their cholesterol-containing analogs; a noticeable difference between the systems was an approx . 10% increase in the segmental order parameters on the addition of amphotericin B to the system containing the alpha-isomer of cholesterol . The concept of a dynamic complexation between amphotericin B and sterol is discussed.

Eur J Clin Microbiol, 1984 Oct, 3(5), 468 - 70
The plasma pharmacokinetics of high dose (1 g) imipenem coadministered with 1 g cilastatin in six normal volunteers; Drusano GL et al.; The plasma pharmacokinetics of imipenem, a beta-lactam antibiotic of the new class of carbapenems, was evaluated by administering 1 g imipenem plus 1 g of the dehydropeptidase inhibitor cilastatin to six healthy male volunteers over 30 min . Subsequently intensive plasma sampling was done for 5.5 h . The volume of distribution of the central compartment was 0.16 +/- 0.04 1/kg; the volume of distribution (area) was 0.28 +/- 0.07 1/kg; the volume of distribution (steady state) was 0.23 +/- 0.03 1/kg . The mean plasma clearance was 10.1 +/- 1.0 1/h/1.73 m2 . Model-independent analysis showed excellent agreement with these values . The terminal excretion half-life was short (1.3 +/- 0.4 h) . For approximately 6 h after administration, the observed plasma levels were above those required to inhibit most nosocomial pathogens in vitro.

Biochem J, 1984 Oct 1, 223(1), 211 - 20
Analysis of the mechanism of chloramphenicol acetyltransferase by steady-state kinetics . Evidence for a ternary-complex mechanism; Kleanthous C et al.; The mechanism of the enzymic reaction responsible for chloramphenicol resistance in bacteria was examined by steady-state kinetic methods . The forward reaction catalysed by chloramphenicol acetyltransferase leads to inactivation of the antibiotic . Use of alternative acyl donors and acceptors, as well as the natural substrates, has yielded data that favour the view that the reaction proceeds to the formation of a ternary complex by a rapid-equilibrium mechanism wherein the addition of substrates may be random but a preference for acetyl-CoA as the leading substrate can be detected . Chloramphenicol and acetyl-CoA bind independently, but the correlation between directly determined and kinetically derived dissociation constants is imperfect because of an unreliable slope term in the rate equation . The reverse reaction, yielding acetyl-CoA and chloramphenicol, was studied in a coupled assay involving citrate synthase and malate dehydrogenase, and is best described by a rapid-equilibrium mechanism with random addition of substrates . The directly determined dissociation constant for CoA is in agreement with that derived from kinetic measurements under the assumption of an independent-sites model.

J Med Chem, 1984 Oct, 27(10), 1295 - 9
Synthesis and in vitro biological evaluation of N-{(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl}-3- (hydroxynitrosamino)-L-alanine (L-alanosine AICO ribonucleoside); Strazzolini P et al.; L-Alanosine {3-(hydroxynitrosoamino)-L-alanine} is an antitumor antibiotic that at the present is undergoing phase II clinical trials . Its mode of action as well as its metabolism has been extensively studied, and the metabolite N-{(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl}-3- (hydroxynitrosoamino)-L-alanine ribonucleotide (L-alanosine AICOR) proved to be an extremely potent inhibitor of de novo purine biosynthesis and is thus primarily responsible for the antitumor activity of the drug . The synthesis of the corresponding ribonucleoside, i.e., N-{(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl}-3- (hydroxynitrosamino)-L-alanine ribonucleoside (L-alanosine AICO ribonucleoside), was accomplished by condensation of a suitably protected derivative of L-alanosine with N-succinimidyl-5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1H-im idazole-4-carboxylate followed by the removal of the protective groups . The biological activity of L-alanosine AICO ribonucleoside was tested in vitro on whole tumor cells and on the isolated enzyme adenylosuccinate synthetase and in vivo on murine experimental leukemia . The compound was found to be inactive in these tests.

Ann Gastroenterol Hepatol (Paris), 1984 Oct-Nov, 20(5), 265 - 70
{Anorectal manifestations of sexually transmissible diseases . Kaposi's sarcoma}; Libeskind M et al.; The proctologist is above all concerned with the known recrudescence of venereal diseases . Examples reviewed are diseases of bacterial origin (syphilis, gonorrhea, soft chancre, donovanosis and chlamydiosis), appropriate antibiotic therapy and diseases of viral origin (herpes, condyloma acuminatum) . Also noted are other bacterial, viral and parasitic diseases and, indeed, cancers of which Kaposi's sarcoma is the example, even though these are not manifested anorectally . New data on Kaposi's sarcoma, its' relationships with venereal disease and AIDS are presented . With these complex problems, the central role of male homosexuality and lowered cellular immunity widens considerably the professional scope of the proctologist.

Chir Ital, 1984 Oct, 36(5), 773 - 84
{Treatment of esophagotracheal and esophagobronchial fistulas secondary to carcinoma of the esophagus}; Forni E et al.; An experience with 16 patients with respiratory tract fistula (RTF) related to carcinoma of the esophagus is presented . The malignant fistula was present at the time of initial presentation and/or before any therapeutic intervention in 11 patients, and developed either during or following a course of radiation therapy in 5 patients . Bronchoscopy examination in 8 patients prior to RTF development showed tracheobronchial invasion or impingement in all . The patients were divided in five groups according to the treatment received . One patient received no specific therapy although was fed via nasogastric tube . Three patients had a feeding gastrostomy . Four patients underwent insertion of a Celestin tube . Three patients were submitted to esophageal exclusion with combinations of cervical esophagostomy, feeding gastrostomy and ligation or complete division of the gastroesophageal junction; drainage of the excluded esophagus was provided by a red rubber catheter . Five patients received by-pass operation: four had Kirschner-Ong operation with gastric by-pass placed substernally and distal esophagus anastomosed to a Roux-en-Y jejunal loop; in one patient an isoperistaltic gastric tube brought to the neck substernally was used for esophageal by-pass . These patients had, by far, the best palliative results with complete relief of their respiratory tract symptoms and restoration of the ability to eat and drink . Substernal gastric by-pass of the RTF is therefore advocated if the general conditions of the patient are improved with the institution of parenteral hyperalimentation and antibiotic therapy.

Rev Fr Gynecol Obstet, 1984 Oct, 79(10), 603 - 7
{Prevention of Chlamydia trachomatis infections in women}; Henrion R; PIP: Chlamydia are a frequent etiologic agent in the chronic salpingitis that has become more and more of a problem in recent years, with its accompanying pelvic pain, ectopic pregnancies, and tubal sterility . Although public health officials, obstetricians and gynecologists, and sexually transmitted disease specialists all agree that prevention would be preferrable to treatment of the resulting tubal lesions and possible neonatal complications, the change of habits necessary for prevention will be difficult to achieve . Infection can be avoided by discouraging early initiation of sexual activity in adolescents, who are apparently particularly susceptible to chlamydial infection, and by discouraging multiple sexual partners since the risk increases appreciably for those having over 3 partners . Condoms and local spermicides with a benzalkonium chloride base offer protection but are poorly accepted by adolescents . IUDs should not be used by adolescents because of the risk of infection . Diagnosis of chlamydia is difficult because about 60% of cases in women are asymptomatic . Persons at high risk because of their patterns of sexual activity should be examined regularly for chlamydia, and tests should be scrupulously performed at all stages and sent to a competent laboratory . All sexual contacts of the chlamydia patient and all their sexual contacts should be treated . An early diagnosis of tubal involvement is difficult but should be pursued through laparoscopy and taking the necessary samples . The public should be educated about the existence, gravity, consequences, and contagiousness of sexually transmitted diseases in such institutions as schools and the military service . Treatment of chlamydia includes early and intensive antibiotic therapy, complete rest, and prolonged use of corticotherapy . An oral contraceptive can be prescribed to prevent development of functional ovarian cysts . Laparoscopic control is essential to ensure that the cure was effective . Return of the infection is associated with a very poor prognosis .

Sex Transm Dis, 1984 Oct-Dec, 11(4 Suppl), 423 - 5
Clinical trial of thiamphenicol therapy for uncomplicated gonorrhea; De Parra CS et al.; The need for a safe drug that is easy to administer and not too expensive prompted a study of treatment of uncomplicated gonorrhea with a single oral dose of 2.5 g of thiamphenicol . Of 169 patients treated, 161 were cured . Of the 92 patients with acute infections, all of the 13 men and 74 (93.7%) of the 79 women were cured . Seventy-seven cases were defined as reinfection; all of the 22 men in this group were cured, as were 52 (94.5%) of the 55 women . Only minor adverse effects were noted . It is concluded that thiamphenicol is a safe and effective antibiotic for therapy of uncomplicated gonorrhea.

J Anim Sci, 1984 Oct, 59(4), 892 - 5
Efficacy of thiopeptin as a growth promotant for growing barrows and gilts--a cooperative study; Cromwell GL et al.; A cooperative study involving 280 crossbred pigs was conducted at three experiment stations (Illinois, Indiana and Kentucky) to evaluate the efficacy of the antibiotic, thiopeptin, as a growth promotant for growing pigs . At each station, two replications of barrows and two replications of gilts (four or five/pen), initially averaging 9.3 kg, were fed a fortified corn-soybean meal basal diet with 0, 5.5, 11, 22 or 44 ppm thiopeptin . The pigs averaged 41.4 kg at the end of the 56- to 57-d experimental period . Daily gain increased quandratically (505, 550, 565, 585, 590 g/d; P less than .001) and feed required per unit of gain decreased quadratically (2.32, 2.26, 2.29, 2.22, 2.22; P less than .15) with increasing levels of thiopeptin . Breakpoint analysis indicated that rate and efficiency of growth were maximized at the 14- and 22-ppm levels of thiopeptin, respectively . Averaged across all levels of thiopeptin, gain was increased by 13.4% and feed/gain by 3.2% in pigs fed the antibiotic . Responses to dietary treatment were similar at each station, with no evidence of a treatment X station interaction for gain (P = .35) or feed/gain (P = .80) . Barrows and gilts performed similarly (558 vs 560 g/d, 2.26 vs 2.26 feed/gain) and there was no evidence of a sex X treatment interaction . From the results of this experiment, we conclude that thiopeptin is an effective growth promoting agent for growing swine.

Antibiotiki, 1984 Oct, 29(10), 751 - 5
{Effect of levorin on the intracellular pool of free amino acids in Ehrlich ascites carcinoma cells}; Gorozhankina IS et al.; Levorene, a polyenic antibiotic, lowered the concentration of amino acids in the cells of Ehrlich carcinoma . The decrease in the intracellular level of the amino acids was due not only to inhibition of their entrance to the cells but also to their increased leaching from the cells . The effect of levorene on the intracellular level of the neutral amino acids was higher than that on the main amino acids which was associated with different sensitivity of the amino acid transport systems to the antibiotic.

J Antimicrob Chemother, 1984 Oct, 14(4), 339 - 48
A simple method for the identification of aminoglycoside-modifying enzymes; van de Klundert JA et al.; In order to study the correlation between the presence of aminoglycoside-modifying enzymes in bacteria and the susceptibility of these bacteria to aminoglycosides, 133 resistant strains were collected, representing the most frequently occurring modifying enzymes in clinical isolates today . Enzymes in these resistant strains were identified by the determination of substrate profiles for eight different aminoglycosides in vitro . Thirteen different enzymes or combinations of enzymes appeared to be present in this collection, whereas in seven cases the resistance appeared to be non-enzyme-mediated . The enzyme activities were not reflected in the bacterial susceptibility data for each antibiotic . Cluster analysis of the combined sensitivity data, with biochemical enzyme analysis as a guideline, proved to be unsatisfactory for the identification of aminoglycoside-modifying enzymes in clinical isolates . Much better results were obtained with a stepwise determination scheme . This method relies upon inhibition zone diameters around commercially available sensitivity discs for six aminoglycoside antibiotics . These zone diameters are compared with empirically established critical values, which are characteristic of an enzyme or group of enzymes . By this procedure proper identification of the enzyme(s) proved to be possible in 84% of the 133 resistant strains . For the evaluation of the method 100 consecutively isolated aminoglycoside resistant clinical isolates were analysed by means of the stepwise scheme and the biochemical method . Results were identical for 97 of the 100 strains.

J Antibiot (Tokyo), 1984 Oct, 37(10), 1253 - 6
Enhancement of mouse immune system by pyrrolomycin B; Umezawa K et al.; Pyrrolomycin B enhanced both humoral immune response and delayed-hypersensitivity against sheep red blood cells in mice . In spleen cell culture it was a weak inhibitor of mitogenesis . However, in combination with concanavalin A, there was stimulation of mitogenesis in spleen cell culture . Pyrrolomycin B also enhanced phagocytosis of yeasts by peritoneal macrophages after in vivo administration to mice . Thus, pyrrolomycin B, formerly isolated as an antibiotic agent, is an immunopotentiator possibly acting on the membrane of lymphocytes or macrophages.

J Antibiot (Tokyo), 1984 Oct, 37(10), 1224 - 30
Interspecific protoplast fusion among macrolide-producing streptomycetes; Ikeda H et al.; From auxotrophic and idiotrophic mutants of Streptomyces fradiae (tylosin producer) and Streptomyces sp . AM 4900 (pikromycin producer) or Streptomyces narbonensis (narbomycin producer), prototrophic fusants were obtained at a low frequency by the protoplast fusion technique . In the cross of S . fradiae 261-27E (mycaminose-idiotroph, ilv) and Streptomyces sp . AM 4900 N3-4, (pikronolide-idiotroph, arg), an unstable prototrophic fusant, strain No . 14, produced a macrolide antibiotic which was not produced by the wild type, parent strains, and the productivity was lost within a few times transfer . It was concluded that the fusant was not a recombinant, but a heterokaryon . On the other hand, relatively stable fusants were obtained from the cross of S . fradiae TBM (mycaminose-idiotroph, met) and S . narbonensis NA12US3 (narbonolide-idiotroph, his, str) at a frequency of 3.2 X 10(-5) . One of the prototrophic fusants produced narbomycin, which is believed to be due to a result of interspecific recombination.

Ann Plast Surg, 1984 Oct, 13(4), 298 - 303
Management of mandibular fractures in unreliable patient populations; Chan DM et al.; There is a high incidence of complications following treatment of fractures of the dentulous mandible at our institution, which has led us to scrutinize the criteria for maintaining teeth in the line of fracture and to evaluate other factors that may compromise healing of the fractured mandible, especially in an unreliable patient population . We have reviewed the opinions of various authors and agree that management decisions must be individualized . We recommend prompt and stable immobilization, adequate observation, use of a "tickle file" to keep track of missed appointments, and long-acting intramuscular prophylactic antibiotic coverage, all of which will help minimize morbidity associated with teeth in the line of mandibular fractures, especially in high-risk patients . We also recommend extraction of fully or partially erupted third molars in the line of fracture as well as deeply carious teeth, severely mobile teeth, or teeth with half or more of their root surface exposed to the fracture line . Finally, we recommend that intraoral rather than extraoral open reduction be considered when teeth are to be extracted in order to avoid contamination with the extraoral environment, to enhance surgical access, and to lower postsurgical morbidity.

Nurse Pract, 1984 Oct, 9(10), 40 - 1, 44-6, 50-2
Preventing diabetic foot problems; Frazin R; Complications of diabetic foot disease may be prevented through regular office followup that includes inspection of the feet and patient education . Peripheral vascular disease and neuropathy are the pathophysiological factors underlying the development of ulcers and gangrene . Evaluation should include careful assessment of the neurological and vascular integrity of the legs and feet, risk factors for underlying disease and self-care abilities . When ulceration occurs, management includes bed rest, appropriate antibiotic therapy, topical care and treatment of any underlying large vessel disease . Worthwhile goals in caring for the diabetic individual's feet include: appropriate choice of shoes; good nail and skin care; excellent blood sugar control; smoking cessation; regular exercise; and maintaining normal blood pressure, cholesterol and triglyceride levels; and infection-free feet . Involving the family, the visiting nurse and/or the podiatrist may be helpful in achieving these goals.

J Am Vet Med Assoc, 1984 Oct 1, 185(7), 792 - 3
Isolation of Actinobacillus lignieresii from enlarged tongue of a horse; Baum KH et al.; In the horse described herein, Actinobacillus lignieresii was associated with a syndrome identical to wooden tongue in cattle . It responded rapidly to systemic sodium iodide and antibiotic therapy . The definitive diagnosis was based on cytologic examination and culture . If actinobacillosis is suspected, immediate treatment with sodium iodide should be instituted along with supportive therapy.

Crit Care Med, 1984 Oct, 12(10), 867 - 70
Blind use of the double-lumen plugged catheter for diagnosis of respiratory tract infections in critically ill children; Zucker A et al.; Transtracheal aspiration, percutaneous lung biopsy, and tracheal aspiration can be dangerous and/or unreliable methods for obtaining specimens of pulmonary secretions for culture . Using a blind technique, we evaluated the efficacy of a double-lumen catheter (DLC) with a polyethylene glycol plug in obtaining specimens of respiratory tract secretions for culture, and compared these results with simultaneously obtained cultures of tracheal aspirates . Twenty-seven intubated children already receiving antibiotic therapy were studied . Sixteen (59%) DLC specimens were sterile, as opposed to only 6 (22%) tracheal aspirates . Only 2 (8%) of the DLC specimens were contaminated . Two DLC specimens yielded significant bacterial growth (at least 10(5) colony-forming units/ml) . Using DLC culture data, there was an 81% success rate in making decisions concerning antibiotic selection . We conclude that blind use of the DLC is a safe and reliable method of obtaining pulmonary secretion specimens for culture.

Ann Surg, 1984 Oct, 200(4), 543 - 53
Radiation to the breast . Complications amenable to surgical treatment; Bostwick J et al.; Major complications of radiation directed to the breast, axilla, and mediastinum were treated in 54 patients from 1974 to 1983 . A classification of these complications facilitates both an understanding of the pattern of injury and the development of a treatment plan . Classification: I . Breast necrosis; II . Radionecrosis and Chest Wall Ulceration; III . Accelerated Coronary Atherosclerosis with Median Sternotomy Wound Failure After Coronary Revascularization; IV . Brachial Plexus Pain and Paresis; V . Lymphedema and Axillary Cicatrix; VI . Radiation-induced Neoplasia . The treatment has evolved during the 10-year study period to excision of the necrotic wound, including any tumor, and closure with a transposed muscle or musculocutaneous flap of latissimus dorsi (II, III, V) or rectus abdominis (I, II, VI) . This strategy reflects a change from primary use of the omentum during the first years of the study . The vascularity, oxygen and antibiotic delivery of these muscle and musculocutaneous flaps promote wound healing, usually with one operation . The transfer of these muscles has not caused significant functional deficits.

Urology, 1984 Oct, 24(4), 375 - 8
Parameatal ducts of glans penis . Structure, symptoms, and treatment of uncommon focus of infection; Gilhooly P et al.; It has been shown that persistent penile irritation and purulent discharge from around the urethral meatus may rarely be caused by inflammation of tiny tubular structures previously known as paraurethral ducts . They appear to be rare embryologic remnants which can be involved in the venereal disease complex . Local excision is the appropriate treatment if symptoms are not responsive to antibiotic therapy.

South Med J, 1984 Oct, 77(10), 1323 - 5
Ampicillin-associated seizures; Hodgman T et al.; Two patients had ampicillin-associated seizures . Although they had complex medical problems, the high serum concentrations of ampicillin at the time of seizures without their recurrence after discontinuing the antibiotic suggest that the seizures were related to the ampicillin therapy.

Arch Surg, 1984 Oct, 119(10), 1189 - 91
Mucormycosis in patients with multiple-organ failure; Aziz S et al.; Mucormycosis in two patients with multiple-organ failure appeared as a cutaneous lesion and spread rapidly . In the first case, wet mounts and potassium hydroxide preparations were unhelpful, but a punch biopsy specimen established the diagnosis . Prompt and extensive debridement and amphotericin B administration arrested the infection . In the second case, virulent progression of the lesion occurred despite limited amputation, debridement, transfer factor, and amphotericin B, but finally responded to further amputation . Diagnosis was made by histologic examination of infected tissue . Both patients shared the following predisposing factors: sepsis, low blood flow, acidosis, multiple-organ failure, and multiple-antibiotic therapy . Although the mucormycosis was controlled, as confirmed in the first case at autopsy and in the second case by clear margins following reamputation, the outcome was fatal in both cases due to other features of multiple-organ failure.

Ann Emerg Med, 1984 Oct, 13(10), 908 - 11
Management of lymphadenitis in childhood: the role of percutaneous needle aspiration; Fleisher G et al.; Bacterial lymphadenitis occurs commonly during childhood, but the preferred initial therapy has not been clearly established . We studied lymphadenitis in children to determine the course of patients with fluctuant and nonfluctuant infections, and to assess the role of percutaneous needle aspiration as a form of therapy . Of 32 patients diagnosed as having lymphadenitis, 30 were followed successfully (26 with initially nonfluctuant and four with initially fluctuant infections) . Fluctuance subsequently developed in four of 26 lymph nodes that were initially firm to palpation . In all eight children with fluctuant lesions the infections were resolved following percutaneous needle aspiration and antibiotic therapy, and 25 of 26 with initially nonfluctuant infections were cured with antibiotic therapy alone or with antibiotics accompanied by percutaneous aspiration when fluctuance developed (four cases) . Thus we recommend initial percutaneous aspiration for the treatment of lymphadenitis whenever abscess formation is detected clinically.

Int J Oral Surg, 1984 Oct, 13(5), 386 - 95
Hyperbaric oxygen treatment of chronic osteomyelitis of the jaws; Van Merkesteyn JP et al.; A review of the literature on treatment of chronic osteomyelitis of the jaws shows that hyperbaric oxygen is often recommended as an adjunct in treatment of this disease . Definite criteria to indicate this treatment and to evaluate the results have not been reported . The results of hyperbaric oxygen treatment of chronic osteomyelitis of the jaws in 16 patients are presented . In contrast to the good results reported in the literature, only 7 of our patients could be considered as cured . The reasons for this discrepancy are discussed . Our results, as well as the data from the literature, indicate that a combined antibiotic and surgical approach is the treatment of choice in chronic suppurative osteomyelitis . However, in chronic diffuse sclerosing osteomyelitis and in patients in whom decortication and antibiotic therapy have failed, hyperbaric oxygen treatment in combination with antibiotics and surgery seems to be indicated.

Clin Haematol, 1984 Oct, 13(3), 557 - 72
Prophylaxis and treatment of infection of the immunocompromised host by granulocyte transfusions; Buckner CD et al.; Granulocyte transfusions are expensive and involve healthy donors in a procedure which is time-consuming, uncomfortable and not without risk . It is therefore important to consider carefully the circumstances which justify their use . The indiscriminate transfusion of inadequate quantities of granulocytes from random donors into sensitized recipients should be discouraged . Severely neutropenic patients with bacterial infection persisting in the face of maximum antibiotic therapy are clearly appropriate recipients of granulocyte transfusion therapy . Well-designed programmes of prophylactic granulocyte transfusion can reduce the acquisition of bacterial infection in granulocytopenic patients . However, there are very few clinical situations in which their use is justified . A wider use of granulocytes must await better techniques of granulocyte procurement and donor selection.

Proc Natl Acad Sci U S A, 1984 Oct, 81(20), 6276 - 80
Photoaffinity labeling and characterization of the cloned purine-cytosine transport system in Saccharomyces cerevisiae; Schmidt R et al.; 8-Azido{2-3H}adenine was used as a photoaffinity label for the purine-cytosine transport system . After irradiation in the presence of the photoaffinity label, the cells were converted into protoplasts, their plasma membranes were purified, and the membrane proteins were extracted and separated by NaDodSO4/PAGE . The radioactivity was specifically incorporated into a protein with a molecular weight of 120,000 . Photoaffinity labeling of this protein could be blocked by irradiation in the presence of natural substrates for the transport system . The molecular weight as determined by NaDod-SO4/PAGE was found to be twice the value calculated from mRNA analysis of the cloned gene . Incubation of exponentially growing cells with tunicamycin, an antibiotic that inhibits glycosylation of proteins, resulted in a 40% decrease in the overall initial uptake rate, which correlates with the reduction of the labeled Mr 120,000 protein . Treatment of the extracted labeled plasma membrane proteins with glycosidic enzymes resulted in disappearance of the Mr 120,000 peak and the appearance of new peaks at Mr 60,000 and Mr 73,000 . These findings indicate that the purine-cytosine transport protein is a glycoprotein.

Neurosurgery, 1984 Oct, 15(4), 475 - 83
Effect of gentamicin and dexamethasone on the natural history of the rat Escherichia coli brain abscess model with histopathological correlation; Neuwelt EA et al.; In a rodent model of Escherichia coli brain abscess, the natural history of the infection was studied and the influence of a glucocorticoid (dexamethasone) and an antibiotic (gentamicin) on the development of brain abscess and the survival of abscess-bearing animals was evaluated . The administration of steroids using three different dosage schedules suppressed the macrophage and glial response, decreased collagen formation, increased the number of pathologically evident bacteria, and decreased host survival . The administration of antibiotics by parenteral routes decreased the number of viable bacteria in the abscess . The simultaneous administration of systemic gentamicin and dexamethasone resulted in increased host survival to a level that was intermediate between that of animals treated with dexamethasone alone and that of those treated with gentamicin alone . Thus, some of the adverse effect of corticosteroids on host survival could be mitigated by the simultaneous administration of antibiotics . Finally, it was observed that the abscess in this model tends to expand along white matter tracks . This path of least resistance may be responsible for the observation that brain abscesses tend to rupture into the ventricle rather than into the subarachnoid space via the cortex.

Clin Pharmacol Ther, 1984 Oct, 36(4), 555 - 65
Neomycin and plasma lipoproteins in type II hyperlipoproteinemia; Hoeg JM et al.; Neomycin, a nonabsorbable aminoglycoside antibiotic, has been shown to exert a hypocholesterolemic effect in man . In a 9-mo, double-blind, randomized, crossover, placebo-controlled clinical trial, the effect of neomycin, 2 gm/day, on plasma lipoproteins, as well as its safety, was described in 20 subjects with type II hyperlipoproteinemia . A 15% (50 mg%) decline in plasma cholesterol concentration was observed with neomycin . Most of this effect resulted from a 41 mg% (16%) decrease in low-density lipoprotein cholesterol concentration . No significant or consistent effect on the concentration of high-density lipoprotein cholesterol was observed . Monthly audiologic and renal evaluation disclosed no oto- or nephrotoxicity . Neomycin treatment in patients with type II hyperlipoproteinemia is an inexpensive and effective means of lowering the concentration of low-density lipoproteins and is free of significant side effects over a 3-mo period.

J Antimicrob Chemother, 1984 Oct, 14(4), 411 - 21
Observations on the toxicity of the combination of gentamicin and mezlocillin in the treatment of patients with acute leukaemia; Rankin EM et al.; In a retrospective study we have compared the toxic side effects related to the use of two antibiotic regimens in the treatment of febrile episodes in neutropenic, leukaemic patients undergoing first remission-induction . Nephrotoxicity was more severe in the gentamicin-mezlocillin (G/M) group: four patients developed oliguric renal failure and two others showed rises in the serum creatinine of more than 0.03 mmol/l . One of the two patients in the gentamicin-ticarcillin (G/T) group who showed nephrotoxicity developed renal failure . Ototoxicity and skin rashes were more commonly observed with G/M than with G/T, and the differences were statistically significant for both ototoxicity (P = 0.0004) and drug rashes (P = 0.02) . The cause of the observed differences in toxicity has not been identified.

J Allergy Clin Immunol, 1984 Oct, 74(4 Pt 2), 573 - 9
Drug-induced skin disease; Kaplan AP; Drug-induced cutaneous reactions encompass a wide variety of rashes that depend in part on route of administration (e.g., contact versus systemic) as well as type of cutaneous response and molecular mechanism underlying the reaction . One such reaction is a type IV immunologic reaction (delayed hypersensitivity) manifest as contact dermatitis and commonly elicited by drugs such as antihistamines, antibiotic ointments, local anesthetics, and paraben esters in cosmetic creams and lotions . A generalized eruption of this sort will occasionally occur with systemic administration of a drug to someone previously sensitized by topical application . Systemic administration of agents can cause nonspecific pruritus or maculopapular eruptions that resemble visual exanthemas . The pathogenesis is unclear and no immune mechanism has been demonstrated . If the drug is continued, exfoliative dermatitis can result . Other types of reactions are urticarial in nature and include acute urticaria/angioedema, erythema multiforme (bullous and nonbullous), Stevens-Johnson syndrome, urticaria in association with serum sickness-like reactions, and urticaria associated with anaphylactoid reactions . In many of these, an allergic reaction in which there is an immunoglobulin (Ig) E-dependent release of mediators in the skin causes hives or swelling . In others, circulating immune complexes may be present, often involving IgG antibody complexed with drug and complement fixation; hives may then be caused by anaphylatoxin release or a concomitant IgE-mediated reaction . In some instances, a cellular reaction may augment the aforementioned inflammatory reactions, perhaps as part of a late-phase reaction or a true delayed hypersensitivity component.

Nippon Sanka Fujinka Gakkai Zasshi, 1984 Oct, 36(10), 1867 - 76
{Peplomycin sensitivity of various types of human gynecological cultured tumor cells}; Ueda M et al.; Various types of human gynecological cultured tumor cells were tested for the sensitivity to Peplomycin (PEP), an effective antitumor antibiotic for squamous cell carcinomas, by the regrowth assay method together with morphological observation . Bleomycin-hydrolase activity of these cell lines was also compared in cell-free extracts by assaying the conversion of Bleomycin into its deamidated from (HPLC method) . SKG-I, SKG-II, SKG-IIIb cells derived from squamous cell carcinoma of the cervix and RKN cells derived from myosarcoma of the ovary were much more sensitive to PEP than other cell lines . PEP was found to be mainly a time-dependent drug, but also concentration dependent . The effect of PEP on cell morphology was characterized by the appearance of enlarged cells and swelling nuclei . The specific activities of Bleomycin-hydrolase in SKG-I, SKG-II, SKG-IIIb cells were shown to be relatively lower than that in other cell lines . These results suggested that cervical squamous carcinoma cells and ovarian myosarcoma cells were sensitive to PEP and Bleomycin-hydrolase activity was one of factors which decided the PEP sensitivity of human cultured tumor cells.

Ann Intern Med, 1984 Oct, 101(4), 435 - 9
Efficacy of intravenous immunoglobulin in primary humoral immunodeficiency disease; Cunningham-Rundles C et al.; Twenty-one patients with primary humoral immunodeficiency were treated for 1 year with a chemically intact immunoglobulin, 300 mg/kg body weight given intravenously every 3 weeks, to compare immunoglobulin levels and clinical status with results achieved after standard treatment with intramuscular immunoglobulin given previously for 1 year . A substantial reduction of specific acute illnesses and antibiotic use was found for 18 of the 21 patients, particularly during the second 6 months of treatment . Average IgG levels before intravenous infusion were increased 243 mg/dL over previous intramuscular pre-injection levels . Adverse effects were recorded for 2.5% of infusions.

J R Army Med Corps, 1984 Oct, 130(3), 183 - 4
Typhoid masquerading as Japanese encephalitis; Henderson A et al.; We describe a variant of typhoid which was clinically indistinguishable from Japanese Encephalitis (JE) . The strongly encephalitic presentation led to a potentially serious delay in starting specific antibiotic therapy . Awareness of the usual form of typhoid is of great importance to Army doctors because of the presence of British soldiers and families in the Dharan area of southern Nepal where both typhoid and JE are endemic.

Jpn J Antibiot, 1984 Oct, 37(10), 1934 - 8
{Experience with sulbactam/cefoperazone in the field of obstetrics and gynecology}; Kohara T et al.; Sulbactam/cefoperazone (SBT/CPZ) was studied for clinical efficacy in the field of obstetrics and gynecology, and following results were obtained: In the treatment of 6 cases of gynecological infection, the clinical efficacy of SBT/CPZ was assessed as excellent in 1 case and effective in 5 cases . Neither adverse effects nor abnormalities in laboratory findings due to SBT/CPZ were observed . Based on these results, SBT/CPZ is considered to be a highly effective antibiotic with clinical efficacy in obstetric and gynecological infections in the daily dosage of 2 g given in two divided doses.

Biochem Pharmacol, 1984 Oct 1, 33(19), 3059 - 62
Streptonigrin-induced deoxyribose degradation: inhibition by superoxide dismutase, hydroxyl radical scavengers and iron chelators; Gutteridge JM; The aminoquinone antitumour antibiotic streptonigrin stimulates deoxyribose degradation in cell-free systems . This degradation is dependent both on reduction of the drug to a semiquinone and on traces of molecular oxygen in the reaction . Inhibition by a variety of hydroxyl radical scavengers and by catalase implicates a radical species with properties similar to the hydroxyl radical . Iron salts appear to play some part in radical formation as DETAPAC and desferrioxamine partly inhibit . Deoxyribose degradation under conditions of low oxygen concentration is strongly inhibited by superoxide dismutase.

Chemioterapia, 1984 Oct, 3(5), 316 - 9
Chemistry and mechanism of action of bleomycin; Mazzei T; Bleomycin (BLM) is an antitumoral antibiotic active against various animal and human tumors . BLM causes a lot of biological effects characteristic of drugs which attack the DNA in cells . The nature of DNA damage consists of the release of bases and single and double-strand breaks . The Fe (II) is a necessary cofactor in the reaction of BLM with DNA . BLM is effective principally against non-dividing cells and against cells in mitotic phase, G2 and S . The various contents of BLM inactivating enzymes in tissues can explain the particular toxicity and therapeutic activity of this drug.

Biochem Pharmacol, 1984 Sep 15, 33(18), 2877 - 80
Molecular models for the interaction of the anti-tumour drug nogalamycin with DNA; Collier DA et al.; Computer graphics and non-bonded energy calculations have been used to model the intercalative binding of the anti-tumour antibiotic nogalamycin, to double-stranded DNA . The drug is predicted to bind preferentially to A-T rich sites . Specific hydrogen bonds to the exocyclic amino group of adenine bases on the 3' side of an intercalative site have been found by the modelling procedure.

Science, 1984 Sep 14, 225(4667), 1115 - 21
The molecular structure of a DNA-triostin A complex; Wang AH et al.; The molecular structure of triostin A, a cyclic octadepsipeptide antibiotic, has been solved complexed to a DNA double helical fragment with the sequence CGTACG (C, cytosine; G, guanine; T, thymine; A, adenine) . The two planar quinoxaline rings of triostin A bis intercalate on the minor groove of the DNA double helix surrounding the CG base pairs at either end . The alanine residues form hydrogen bonds to the guanines . Base stacking in the DNA is perturbed, and the major binding interaction involves a large number of van der Waals contacts between the peptides and the nucleic acid . The adenine residues in the center are in the syn conformation and are paired to thymine through Hoogsteen base pairing.

J Biol Chem, 1984 Sep 10, 259(17), 10814 - 22
Two distinct mechanisms for taurocholate uptake in subcellular fractions from rat liver; Simion FA et al.; As part of the enterohepatic circulation, hepatocytes take up bile acids from the intestines via the hepatic portal blood using a sodium-dependent carrier mechanism and resecrete the bile acids into the bile . In order to assess whether intracellular organelles are involved in the transcellular secretion of bile acids, we measured directly the ability of purified subcellular fractions of rat liver to take up taurocholate using a Millipore filtration assay . Two distinct uptake mechanisms can be discerned, one localized in the plasma membranes and the other in the Golgi and smooth microsomal fractions . Plasma membranes prepared by the method of Fleischer and Kervina (Fleischer, S., and Kervina, M . (1974) Methods Enzymol . 31, 6) take up taurocholate in a saturable manner with an apparent Vmax of 2.4 nmol min-1 mg protein-1 and a Km of 190 microM at 37 degrees C . After preincubation of the membranes with K+ ions, a sodium gradient (100 mM outside) stimulates the uptake rate by 90% with the observed Km unchanged . The stimulation is inhibited by phalloidin but not by bromosulfophthalein . Bile canalicular plasma membranes made according to Kramer et al . (Kramer, W., Bickel, U., Buscher, H . P., Gerok, W., and Kurz, G . (1982) Eur . J . Biochem . 129, 13-24) do not take up taurocholate . The transport by Golgi vesicles and smooth microsomes differs from that in the plasma membrane fraction in that it is not stimulated by a sodium gradient, has a Vmax of 12 nmol min-1 mg protein-1 and a Km of 440 microM at 37 degrees C, and is inhibited by bromosulfophthalein but not by phalloidin . Taurocholate uptake into smooth microsomes is abolished by filipin, an antibiotic that complexes with cholesterol to disrupt the membrane . This suggests that taurocholate uptake occurs into a nonendoplasmic reticulum subfraction since endoplasmic reticulum membranes contain negligible amounts of cholesterol . Little uptake was observed using rough microsomes or mitochondria . A model of transhepatic transport compatible with our observations is that taurocholate uptake into the cytoplasm occurs via the plasma membranes on the sinusoidal side of the hepatocyte; taurocholate is then taken up into smooth vesicles and the Golgi complex and is secreted into the bile by exocytosis as the vesicles fuse with the canalicular plasma membranes.

J Biol Chem, 1984 Sep 10, 259(17), 10801 - 6
A revised primary structure for neocarzinostatin based on fast atom bombardment and gas chromatographic-mass spectrometry; Gibson BW et al.; The amino acid sequence of the antitumor protein neocarzinostatin was revised on the basis of mass spectrometric studies . Gas chromatographic mass spectrometry on the O-trimethylsilyl polyaminoalcohol derivatives of peptide mixtures derived from tetra S-carboxymethyl-neocarzinostatin were used to partially sequence neocarzinostatin . In addition, fast atom bombardment-mass spectrometric experiments on neocarzinostatin and its tryptic fragments gave the molecular weights of various peptides and, in some cases, partial sequence information . The revised sequence involved reordering of two chymotryptic peptides, the identification of a new di- and tripeptide sequence (Ala-Asp and Ala-Ser-Thr), the repositioning of Trp at position 39, and the assignment of the remaining Asx residues . The revised structure for neocarzinostatin (Mr = 11,105) now shows considerable homology with the other antitumor antibiotic proteins macromomycin and actinoxanthin.

Circulation, 1984 Sep, 70(3 Pt 2), I182 - 6
Patient status 10 or more years after 'fresh' homograft replacement of the aortic valve; Penta A et al.; One hundred and forty consecutive patients from 12 to 74 years old (mean 52) who underwent isolated elective aortic valve replacement with antibiotic-sterilized homografts have been followed for 10 to 13 (mean 11) years . There were four (2.9%) early and 48 (34.3%) late deaths . The overall survival rate was 81% at 5 years and 65% at 10 years . Valve failure occurred in 37 (26.4%) patients and was due to degeneration in 27 (19.3%), technical failure in three (2.1%), and endocarditis in seven (5%) . Freedom from valve failure was 90% at 5 years and 72% at 10 years; the mean rate of valve degeneration was 1% per year up to 5 years, 2% from 5 to 8 years, and 5% from 8 to 10 years . Functional evaluation of the patients retaining their original homograft at 10 years showed excellent or good results in 82% and fair or poor results in 18% . A multivariate regression analysis of factors influencing survival and valve failure showed that older age of the patient (p less than .01) and the development of postoperative left bundle branch block (p less than .05) adversely affected survival, and that older age and sex (female) of the patient (p less than .01), the type of original valve lesion (stenosis) (p less than .05), and the interval between death and dissection of the grafts (p less than .01) were good predictors of valve failure.

J Pharm Sci, 1984 Sep, 73(9), 1326 - 8
The effects of salicylate on the rectal absorption of phenylalanine and some peptides, and the effects of these peptides on the rectal absorption of cefoxitin and cefmetazole; Nishihata T et al.; The disappearance of phenylalanine and phenylalanylglycine from a perfusate circulated across rat rectal tissue was enhanced significantly in the presence of salicylate or 5-methoxysalicylate at pH 4.5, 7.4, and 8.5 . The disappearance of di-, tri-, and tetraphenylalanine from a perfusate at pH 7.4, although facilitated by the presence of salicylate and 5-methoxysalicylate, was also fairly substantial when no adjuvant was present . These peptide analogues of phenylalanine also enhanced the rectal absorption of cefoxitin and cefmetazole, two highly water soluble antibiotics . Phenylalanine and phenylalanylglycine, both poorly absorbed across the rectal membrane when administered alone, did not enhance the rectal absorption of either antibiotic.

Aust Fam Physician, 1984 Sep, 13(9), 665 - 72
Acute salpingitis . Diagnostic and therapeutic dilemmas; Gilbert GL; Acute salpingitis is occurring with increasing frequency among sexually active young women and is associated with a significant risk of long term morbidity, especially infertility . Clinical diagnosis is difficult because symptoms and signs are nonspecific and their severity is not always commensurate with the tubal pathology . No antibiotic is ideal; the choice should depend on the most likely pathogen in each patient and the severity of her disease.

Pediatr Med Chir, 1984 Sep-Oct, 6(5), 691 - 3
{Ingestion of caustics in childhood: proposal for a therapeutic protocol}; Canavese F et al.; Caustic ingestion is a traumatic event not rare in the infancy . The authors, after a brief discussion of their cases and after a revision of the literature, propose a therapeutic protocol for the treatment of caustic ingestion in the infancy . This protocol is based on the esophagoscopy in the first day and on the antibiotic and corticotherapy in the first two weeks . When there is an esophageal stenosis, the authors propose weekly esophageal dilatations.

Jpn J Antibiot, 1984 Sep, 37(9), 1603 - 6
{Fundamental and clinical studies of intravenous drip infusion of micronomicin in respiratory tract infection}; Oshitani H et al.; A study was carried out with the aminoglycoside antibiotic micronomicin (MCR) to determine its clinical efficacy in respiratory infections on the one hand and its serum levels on the other . MCR was administered in single dose of 60 mg twice daily by intravenous drip infusion over 1 hour to 5 patients with infections aggravation of chronic bronchitis and 3 with pneumonia . Of the total of 8 patients treated, 3 had remarkable and 4 had good responses with a response rate of 87.5%, while 1 has no benefit . Adverse effects on the clinical picture or on laboratory test results were not observed . The peak serum concentration of MCR after a 1.5 hours drip infusion of 90 mg was 7.74 micrograms/ml . In view of the risk of adverse effects, the serum concentration lay on appropriate levels . It is expected therefore that the intravenous drip infusion of MCR will be of particular interest in the treatment of relapse of chronic bronchitis and pneumonia.

Biochem Int, 1984 Sep, 9(3), 369 - 77
Phosphorylation of membrane proteins in monensin-resistant mutant of Chinese hamster ovary cell with altered insulin-receptor activity; Ono M et al.; A Chinese hamster ovary (CHO) cell mutant resistant to the Na+/K+ ionophoric antibiotic, monensin, is partly defective in insulin-receptor activity . Growth of the monensin-resistant mutant required higher dose of insulin in defined medium than the parental CHO cell . Membrane proteins of CHO and a monensin-resistant clone, MonR-31, were compared for their capacity to be phosphorylated by endogenous phosphorylation enzyme in vitro in the absence or presence of insulin . Several membrane proteins of CHO were more highly phosphorylated as compared with MonR-31 in either the absence or presence of insulin.

J Antibiot (Tokyo), 1984 Sep, 37(9), 1066 - 75
Pharmacokinetics of rifapentine, a new long lasting rifamycin, in the rat, the mouse and the rabbit; Assandri A et al.; A study on the pharmacokinetics of rifapentine, a new long-lasting rifamycin, has been carried out in the rat, the mouse and the rabbit . The investigation was made using either radioactive or unlabelled rifapentine and both the total 14C and the unchanged compound were assayed . In the rat, the overall evidence obtained was: the oral absorption of rifapentine into central compartment, due to its poor water solubility, appears to be dose-dependent with a satisfactory oral absorption (84%) after a dose of 3 mg/kg, lower (65%) after 10 mg/kg; the antibiotic undergoes rapid liver uptake while it diffuses into the tissue compartment more slowly, with particular affinity for the adrenals, pancreas and kidneys; concentrations higher than in plasma were also measured in the lungs; elimination of rifapentine from the blood and tissue compartments suggests a non linear capacity-limited kinetics where the terminal elimination phase has monoexponential course . Terminal plasma half-life ranged between 14 and 18 hours; the compound is eliminated mainly via the bile with the feces (92% of dose) . In mice rifapentine shows a kinetic profile resembling that obtained in rats, whereas in rabbits is metabolized and/or eliminated much more rapidly with a half-life of only 1.8 hours.

Ann Otol Rhinol Laryngol, 1984 Sep-Oct, 93(5 Pt 1), 464 - 7
Spontaneous perforation of the esophagus as a manifestation of dermatomyositis; Thompson JW; Spontaneous perforation of the esophagus evolving into a retropharyngeal abscess in a child with severe dermatomyositis is reported . Clinical presentation and successful management are discussed . Aggressive surgical debridement with extensive drainage, multiple antibiotic coverage, and careful steroid management are advocated . The histopathology and clinical presentation of dermatomyositis as a type of polymyositis are discussed as pertinent to the otolaryngologic clinician . The literature is reviewed and results of a retrospective analysis of head and neck manifestations are reported in 50 children with dermatomyositis treated at Children's Hospital, Los Angeles, over the past 20 years.

J Pediatr Orthop, 1984 Sep, 4(5), 630 - 2
Vitamin K deficiency presenting with hemarthrosis; Naveh Y et al.; A breast-fed 25-day-old infant was hospitalized because of swelling and tenderness of the left leg, developed after mild rotary motion of the leg by his brother . Radiographic examination showed widening of the left articular hip joint space . On the day of admission, a presumptive diagnosis of septic arthritis was entertained, and antibiotic therapy was instituted . Following profuse bleeding from sites of skin punctures, coagulation studies were performed . Prothrombin time and partial thromboplastin time were prolonged . Administration of phylloquinone (vitamin K1) resulted in rapid normalization of coagulation . Differential diagnosis between hemarthrosis resulting from vitamin K deficiency and septic arthritis with disseminated intravascular coagulation is a matter of great importance in such patients.

South Med J, 1984 Sep, 77(9), 1165 - 7
Suppurative pylephlebitis due to pseudodiverticulosis coli; Rodning CB et al.; Patients manifesting suppurative pylephlebitis and intrahepatic abscess formation secondary to pseudodiverticulosis coli and acute diverticulitis are uncommon, but have very high morbidity and mortality . As illustrated by this case report, the symptoms and signs such a patient manifests are nonspecific and the diagnostic modalities available may be insufficiently sensitive . The therapeutic options available at present are excision and drainage of any detected extrahepatic or intrahepatic septic focus and prolonged antibiotic administration.

J Am Vet Med Assoc, 1984 Sep 1, 185(5), 533 - 4
Vaginal perforation after coitus in three mares; Held JP et al.; Three cases of vaginal perforation after coitus are discussed . The most consistent clinical sign is a small amount of blood escaping from the vulvar lips immediately after breeding . Secondary infection and posttraumatic swelling may cause abdominal pain due to rectal impaction . Treatment with high levels of an appropriate antibiotic is important to reduce the risk of a severe infectious peritonitis . The use of artificial insemination or a breeding roll to prevent full intromission is recommended.

Blood, 1984 Sep, 64(3), 607 - 13
Changes in activities and isozyme patterns of glycolytic enzymes during erythroid differentiation in vitro; Nijhof W et al.; Late committed progenitor cells of erythropoiesis, CFU-E (colony-forming unit--erythroid), were isolated from mouse spleens to near homogeneity by a three-step enrichment procedure . The procedure included a four-day pretreatment of bled mice with the antibiotic thiamphenicol, a recovery period of 3 1/2 days, followed by centrifugal elutriation and Percoll density gradient centrifugation of the spleen cells . This practically pure CFU-E population was used to study some aspects of erythroid differentiation in vitro . Colony growth, as well as morphology and glycolytic enzyme activities of cells isolated at selected times of the 48-hour culture period, were determined . Marked declining activities of several enzymes, including hexokinase, phosphofructokinase, aldolase, enolase, pyruvate kinase, and glucose-6-phosphate dehydrogenase, were observed during in vitro differentiation . The activity of diphosphoglycerate mutase was almost absent in the CFU-E, but progressively increased during differentiation . The isozyme distribution of aldolase and enolase did not change during CFU-E in vitro differentiation into the reticulocyte . Hexokinase (HK) in the CFU-E contained mainly a double-banded type I isozyme, in addition to a minor amount of HK II . During differentiation, a shift was noticed within the double-banded HK I region, whereas HK ii disappeared after one cell division . Pyruvate kinase in the CFU-E was characterized by the presence of both the K-type and the L-type isozyme and hybrids of these isozyme types . During in vitro differentiation, the production of the K-type isozyme rapidly stops in favor of the L type.

Vet Med (Praha), 1984 Sep, 29(9), 549 - 62
{The effect of prolonged whole-body gamma irradiation of 6,7 Gy and 4,8 Gy (700 and 500 R) on the trypsin inhibiting activity (TIA) of blood, the cervical mucus and the morphological structure of the cervix in ewes}; Molnarova M et al.; The pattern of changes in the trypsin-inhibition activities (TIA) of blood plasma, cervical mucus and in the morphological structure of cervix was studied in ewes exposed to 60Co radiation for seven and five days, the radiation doses being 6.7 Gy and 4.8 Gy (700 and 500 R) . During exposure, the group of ewes irradiated with 4.8 Gy was given the Roboran vitamin premix in addition to standard feed . After termination of irradiation the animals in this trial were given the ampicillin antibiotic (5250 mg) . TIA was determined from the retardation of the hydrolysis of the synthetic substrate N-alpha-tosyl-p-nitroanilide (TAPA) by bovine trypsin; the TIA was expressed as the percentage of inhibited trypsin . As found on the day of the termination of irradiation, almost all the studied TIA values of blood plasma and cervical mucus were increased in the irradiated animals, the range being from 103.1 to 155.0% of the levels for non-irradiated ewes . A reduction was recorded only in total TIA of blood plasma in the group irradiated with the dose of 6.7 Gy (83.1% of the values for non-irradiated animals) . In the group of animals irradiated with 4.8 Gy and fed no Roboran, the TIA of cervical mucus was observed to decrease to 92.4% . When evaluating the average TIA of different test groups throughout the experiment it was found that all the studied TIA values of the irradiated animals increased within a range from 104.1 to 184.0% of the values for untreated ewes . It was only in the average values of total TIA in blood plasma that, after irradiation with 6.7 Gy, a decrease to 92.7% of the level without irradiation was recorded . It was found during the study of changes in the proportions of glands in the stroma and changes in epithelium thickness in the mucous membrane of cervix uteri that the irradiated ewes had the epithelium thickness reduced to 95.3%-65.5% and that their stromal gland number decreased to 75.4%-79.7% of that recorded in non-irradiated animals . It was only in the group given a Roboran supplement that an increase to 123.7% of the gland number for untreated ewes was recorded on the tenth day after the termination of irradiation.

Cephalalgia, 1984 Sep, 4(3), 171 - 8
Reversible cerebral arteriopathy associated with the administration of ergot derivatives; Henry PY et al.; Three cases of intracranial arteriopathy associated with the administration of ergot derivatives are reported . In the first case, excessive doses of dihydroergotamine and of ergotamine tartrate seemed to be the cause, but simultaneous treatment with an antibiotic and the existence of a cytomegalovirus infection could have favoured the arteriopathic process . The second patient also received excessive doses of these two drugs, but in addition she was taking oestrogen and progesteron containing contraceptives . In the third case, an intravenous injection of methylergometrine in a dose of 0.2 mg seemed to have initiated the arteriopathy . Arteriograms were comparable in all three cases, with segmental stenosis of several cerebral arteries, whereas internal carotid and vertebral arteries remained normal . In the first case a control cerebral arteriography was normal one month later . These findings suggest that widespread cerebral arteriopathy can appear in subjects who chronically abuse ergotamine tartrate.

J Neurosurg, 1984 Sep, 61(3), 430 - 9
Cerebrovascular permeability and delivery of gentamicin to normal brain and experimental brain abscess in rats; Neuwelt EA et al.; Antibiotics vary widely in their ability to penetrate the blood-brain barrier . In studies of 70 rats, the permeability of the normal blood-brain barrier to gentamicin was shown to be poor . In experimental brain abscesses, during the cerebritic stage of development, the penetration of intravenous antibiotics was increased compared to normal brain but was very inconsistent . Antibiotic delivery to brain abscess was not significantly altered with the administration of high-dose steroids, but the macrophage and glial response was markedly decreased with high-dose steroid therapy . Reversible osmotic blood-brain barrier modification with mannitol increased the delivery of gentamicin both to brain abscess and to the surrounding brain . It also resulted in more consistent tissue drug levels . The clinical implications of these studies suggest that, because of the inconsistent delivery of gentamicin to brain abscess, the therapeutic efficacy of medical management alone may be quite variable . This mode of therapy could possibly increase the efficacy of medical management of brain abscesses, especially in patients with multiple or surgically inaccessible brain abscesses.

Klin Monatsbl Augenheilkd, 1984 Sep, 185(3), 174 - 6
{Evaluation of infectious, inflammatory external eye diseases}; Bialasiewicz AA et al.; Over a period of 4 months the authors observed 240 outpatients with 302 "red eyes." Oculogenital strains of Chlamydia trachomatis were diagnosed in 12.5% of these cases . Bacterial monoinfections were found in 13.9%, coinfections in 63.9% . The remaining 9.7% included Candida sp . (4%) and Herpes I (1.4%) infections, while 4.3% remained unidentified . Allergic conjunctivitis and "dry eye" syndromes were not considered separately in this study . Specific antibiotic therapy improved the clinical condition due to "saprophytic" bacterial coinfections, indicating the pathogenic importance of this type of infection.

J Antimicrob Chemother, 1984 Sep, 14(3), 285 - 9
Extraction of ceftazidime in bone; Hughes SP et al.; The extraction of ceftazidime has been measured in bone by means of the outflow dilution technique following injection into the perfused nutrient artery of the canine tibia . The instantaneous extraction was found to be 0.71 +/- 0.18 and the net extraction was 0.55 +/- 0.25 (mean +/- S.D . n = 5) . The extraction of this antibiotic is relatively high and this experiment demonstrates the fact that antibiotics leave capillaries in bone and pass into the fluid spaces where they can act on pathogenic organisms.

South Med J, 1984 Sep, 77(9), 1115 - 7
Factors contributing to delay in diagnosis of bacterial meningitis; Dunn DW; I reviewed factors contributing to diagnostic delay in 12 children who had symptoms of meningitis for more than three days before diagnosis . Prior antibiotic therapy was more common in children with delayed diagnosis . Parental factors included possible neglect in one child and passivity and failure to recognize the seriousness of the illness in six children . Physicians failed to recognize prodromal symptoms in five cases . A lack of continuity of care was a contributing factor in nine cases.

J Manipulative Physiol Ther, 1984 Sep, 7(3), 175 - 8
Vertebral osteomyelitis as another cause of low back pain: case report; Huslig EL; A case is reported of a 47 year old man with an insidious onset of low back pain while hospitalized for septicemia . The etiology was not investigated and pharmacologic therapy was instituted . Several weeks after discharge, the patient presented to our chiropractic college clinic for the diagnosis and therapy for his low back pain . Radiologic examination of the lumbar spine revealed classic signs of a vertebral osteomyelitis . Manipulative therapy was contraindicated and the patient was referred for biopsy and appropriate antibiotic therapy . A review of the clinical presentation and appropriate diagnostic protocol are presented.

J Clin Immunol, 1984 Sep, 4(5), 348 - 58
Monocyte procoagulant activity in Whipple's disease; Ottaway CA et al.; We have studied the expression of procoagulant activity by the circulating mononuclear cells of four patients with Whipple's disease . There was a spontaneous expression of procoagulant activity in two patients with active untreated Whipple's disease . This activity was shown to originate in the monocyte fraction of the mononuclear cells and was demonstrated to cleave prothrombin directly . This prothrombinase activity was not Factor Xa, because it was not neutralized by anti-Factor X serum and was not inhibited by an established panel of Factor Xa inhibitors . The prothrombinase activity was not expressed by the monocytes of these patients following 8 weeks of antibiotic therapy, by which time the patients' symptoms resolved, and was not found in two patients previously treated for Whipple's disease who were in clinical remission or in normal subjects . Serial studies in one patient with active disease showed that monocytes failed to express increased prothrombinase within 2 weeks of antibiotic therapy . A second procoagulant activity was produced in response to endotoxin (LPS) by cells from controls and patients with Whipple's disease and was identified as thromboplastin . These observations suggest that circulating monocytes of patients with active Whipple's disease are endogenously stimulated to express prothrombinase activity, which may contribute, at least in part, to the pathophysiology of this condition.

Endocrinology, 1984 Sep, 115(3), 904 - 10
Dependence of cyclic nucleotide production and luteinizing hormone receptor formation upon ribonucleic acid synthesis in cultured rat granulosa cells; Knecht M et al.; The role of newly synthesized RNA in the differentiation of granulosa cells isolated from diethylstilbestrol-treated immature rats was studied during culture with actinomycin D . Choleragen-induced LH receptor formation and cGMP production at 48 h were completely inhibited by actinomycin D (greater than or equal to 100 ng/ml) added as late as 20 h after the initiation of culture and were partially reduced by addition of the antibiotic from 30-48 h . In contrast, addition of actinomycin D to freshly prepared cells enhanced choleragen-stimulated cAMP accumulation during the 48-h culture period . This effect was caused by both elevation of adenylate cyclase activity at 3 and 6 h of culture and inhibition of choleragen-induced phosphodiesterase activity during culture . The increase in cAMP production by actinomycin D was confined to the first few hours of culture, since the antibiotic did not enhance cAMP levels when added after 3 h and significantly reduced cAMP accumulation when added from 20-48 h of culture . Actinomycin D inhibited choleragen-stimulated incorporation of {3H}uridine into RNA of freshly prepared cells by 65% and reduced both RNA synthesis and incorporation of {3H}leucine into protein at 20 and 48 h of culture by approximately 90% . In untreated cells, RNA and protein synthesis and phosphodiesterase activity increased to a larger extent from 20-48 h than after choleragen treatment, but did not lead to elevated cAMP levels or LH receptors . These results suggest that the cAMP-induced syntheses of RNA and protein that are specific for increases in cGMP production and LH receptor formation occur predominantly during the second day of granulosa cell culture . In contrast, cAMP production can be markedly altered by changes in RNA and protein syntheses during the first hours of culture.

J Antimicrob Chemother, 1984 Sep, 14 Suppl B, 117 - 23
Cefotaxime in the cerebrospinal fluid and serum in patients with purulent meningitis; Peretti P et al.; Cefotaxime concentrations in the cerebrospinal fluid and serum were determined in patients with purulent meningitis by means of a simple, rapid and reproducible method in agar medium . The CSF concentrations of cefotaxime fluctuated around 4 mg/l . The pharmacokinetics of the antibiotic in relation to the integrity of the blood-brain barrier was studied by means of an assay of the albumin and IgG present in the cerebrospinal fluid and in the serum.

J Antimicrob Chemother, 1984 Sep, 14 Suppl B, 113 - 6
Serum and tissue concentrations of intravenous cefotaxime during aortic surgery; Robbs JV et al.; Ten patients submitted to prosthetic aortic replacement received repeated intravenous bolus doses of cefotaxime (1 g) during induction of anaesthesia and at 2 hourly intervals during the operation . Hourly blood samples were taken and serum cefotaxime concentrations measured using high performance liquid chromatography . Subcutaneous fat, aortic and peripheral arterial wall samples were taken at various intervals intra-operatively, and tissue antibiotic levels were determined by bio-assay using an agar well diffusion method . Mean serum levels were consistently in excess of 50 mg/l which exceeds the MIC90 of virtually all aerobic and anaerobic pathogens . Tissue levels obtained exceeded the MIC90 of most pathogens . Cefotaxime would appear to provide adequate perioperative prophylactic cover in the dosage regimen used.

J Am Vet Med Assoc, 1984 Sep 1, 185(5), 511 - 6
Swine diseases transmissible with artificial insemination; Thacker BJ et al.; The transport of fresh and frozen semen to be used for artificial insemination creates a mode of disease transmission between farms . Normally, semen contains a number of nonpathogenic bacterial contaminants; however, excessive bacterial contamination can result in infertile matings . Contamination with a known pathogen, eg, Brucella suis, could initiate a serious outbreak of disease in a recipient herd . Methods to minimize bacterial contamination of semen include sanitary collecting and processing of semen, isolation of boards from certain pathogens, and the addition of appropriate broad spectrum or combination antibiotics to the semen . Mycoplasmas also have been isolated from semen, although transmission by this route is unlikely . The addition of an appropriate antimycoplasmal antibiotic to semen may be warranted in some situations . Numerous viruses have been detected in semen . Their exclusion from semen is especially critical because of their ability to survive in frozen semen . These viruses include pseudorabies virus, porcine parvovirus, enterovirus, adenovirus, vesicular disease virus, and African swine fever virus . The likelihood of disease transmission is greater with the introduction of a boar into a herd than through the use of fresh or frozen semen . We believe that artificial insemination allows for the introduction of new genetics into a breeding program, with minimal risk of disease transmission.

J Mol Biol, 1984 Aug 15, 177(3), 563 - 5
Crystallization and preliminary X-ray diffraction studies of colicin E3 immunity protein; Shoham M et al.; Immunity protein, an inhibitor of the ribonuclease activity of the protein antibiotic colicin E3, crystallizes in the orthorhombic space group C222 with cell dimensions a = 78.7 A, b = 54.1 A, c = 36.1 A and one molecule of Mr 9800 per asymmetric unit . The crystals are suitable for high resolution X-ray analysis.

Eur J Biochem, 1984 Aug 15, 143(1), 23 - 6
Effect of P and A site substrates on the binding of a macrolide to ribosomes . Analysis of the puromycin-induced stimulation; Siegrist S et al.; The puromycin-induced stimulation of {3H}dihydrorosaramicin binding is due to a twofold increase in affinity of the macrolide antibiotic, with no change in the number of binding sites . Conversely, the binding of {3H}puromycin (A site) is stimulated by rosaramicin . The synergistic effect observed between the two antibiotics can be explained by a conformational change with positive effect, which occurs at the level of their binding sites . Various effectors of {3H}dihydrorosaramicin binding have been tested . Adenosine and dimethyladenosine stimulate the binding; phenylalanine, uridine and gougerotin (A site) have no effect whereas AMP, ADP, ATP, GTP, puromycin 5'-phosphate and lincomycin (P site) are inhibitors . These results point to the importance of the purine moiety in the stimulatory effect and of the phosphate function in reversing this effect . It is concluded that rosaramicin binds to the ribosomal P site and that the synergism observed between rosaramicin and puromycin may be related to interactions between the A and P sites.

Nucleic Acids Res, 1984 Aug 10, 12(15), 6159 - 68
Characterization of an adduct between CC-1065 and a defined oligodeoxynucleotide duplex; Needham-VanDevanter DR et al.; CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis . The drug binds covalently through N-3 of adenine and lies within the minor groove of DNA . Previous studies indicated that CC-1065 reacted with adenine in DNA to yield a thermally labile product that could be used to reveal its sequence specificity . These studies also provided insight into a DNA sequence (5'-CGGAGTTAGGGGCG-3') which should bind one molecule of CC-1065 in an unambiguous manner . This sequence, which contains the CC-1065 adenine binding site within the sequence 5'-TTA-3' was chemically synthesized together with the complementary strand . CC-1065 reacted with the oligoduplex to give an adduct that maintained the B-DNA form and had a final CD spectrum similar to those of the CC-1065 complexes formed with calf thymus DNA . The above 14mer was 5' end-labelled with 32P, annealed with its complementary strand, reacted with CC-1065 and heated . Drug-mediated strand breakage was evaluated on a sequencing gel . A single break occurred in the labelled strands to give a fragment that migrated as an 8.5mer; subsequent piperidine treatment produced a fragment that migrated as a 7mer, which is the size expected from the known binding of CC-1065 at adenine in 5'-TTA-3' sequences.

J Biol Chem, 1984 Aug 10, 259(15), 9563 - 8
The action of virginiamycin M on the acceptor, donor, and catalytic sites of peptidyltransferase; Chinali G et al.; Virginiamycin M inhibits both peptide bond formation and binding of aminoacyl-tRNA to bacterial ribosomes, and induces a lasting inactivation of the 50 S subunit (50 S) . In the present work, the effects of this antibiotic on the acceptor and donor sites of peptidyltransferase have been explored, in the presence of virginiamycin M as well as after its removal . Virginiamycin M inhibited the binding of puromycin to ribosomes and reduced both the enzymatic and nonenzymatic binding of Phe-tRNA to the A site by inducing its release from the ribosomes (similar effects were observed with 50 S), whereas the antibiotic had no effect on the binding of unacylated tRNAPhe to the same site . Moreover, virginiamycin M caused Ac-Phe-tRNA or Phe-tRNA to be released from the ribosomal P site, when complexes were incubated with unacylated tRNA, elongation factor G, and GTP (similar finding with 50 S) . Instead, peptide bond formation between Ac-Phe-tRNA positioned at the P site and Phe-tRNA at the A site was found to take place, albeit at a very low rate, in the presence of the antibiotic . The overall conclusion is that both the acceptor and donor substrate binding sites of the peptidyltransferase, which interact with the aminoacyl moiety of tRNA, are permanently altered upon transient contact of ribosomes with virginiamycin M.

J Fam Pract, 1984 Aug, 19(2), 185 - 90
The treatment of acute bronchitis with trimethoprim and sulfamethoxazole; Franks P et al.; Sixty-seven previously healthy patients with acute bronchitis were randomized and treated with either a fixed dose of trimethoprim and sulfamethoxazole or placebo for seven days . All outcomes examined showed a trend favoring the use of antibiotic, with statistically significant differences for cough, night cough, mean temperature, and use of antihistamines or decongestants . Night cough occurred on 84 percent of nights in the control group vs 56 percent in the antibiotic group (P = .003) . Cough occurred on 99 percent of days for patients in the control group vs 93 percent of days for patients in the antibiotic group (P = .05) . Mean temperature over the seven nights was 37.3 degrees C in the control group vs 36.9 degrees C in the antibiotic group (P = .004) . The use of antihistamines and decongestants was reduced from 32 percent of days in the control group to 6 percent of days in the antibiotic group (P = .005) . Patients in the antibiotic group worked 73 percent of days vs 55 percent of days for patients in the control group, which was significant when patients were stratified by the appearance of their sputum on Gram stain (P = .006) . Smoking history was not found to help predict the response to antibiotic therapy.

Vestn Khir Im I I Grek, 1984 Aug, 133(8), 83 - 6
{Treatment of suppurative post-traumatic gonitis}; Trubnikov VF et al.; Results of the treatment of 47 patients with purulent gonites enabled the authors to recommend a method of complex treatment with using microartrotomy, drainage of the anterior and posterior portions of the articulation, prolonged running lavage of the articulation cavity by antiseptics in combination with massive antibiotic and immune therapy and other means of the correction of homeostasis . Near and late results were good.

Antimicrob Agents Chemother, 1984 Aug, 26(2), 263 - 5
Tetracycline diffusion through phospholipid bilayers and binding to phospholipids; Argast M et al.; The ability of tetracycline to pass through phospholipid bilayers by diffusion was investigated . Liposomes did not retain enclosed tetracycline . Accumulation of tetracycline was observed with liposomes containing entrapped Tet repressor protein . These results indicate that the drug can pass through lipid bilayers . The antibiotic was also shown to bind to liposomes and isolated phospholipids.

Unfallchirurgie, 1984 Aug, 10(4), 177 - 81
{Hematogenous osteomyelitis of the femur in elderly patients--special forms of pathogenesis}; Geiselhart HP; We present two cases of hematogenous osteomyelitis of the femur in patients who have undergone vascular surgery . We describe the course of disease, the diagnostic considerations and the therapeutic measures . Typical is the painfullness without recognizing the cause during the first days, more or less signs of inflammation of the organism, elevation of ESR . Only with distinct delay there are local signs of inflammation . Not before ten days the normal x-ray shows periosteal reactions and areas of lysis, sooner you can find indications in the CT scan (gas, changed density) . After combined antibiotic and surgical treatment one case is healed, in the other occurs spontaneous fracture and amputation, and because of relapse in the stump exarticulation . In the latter case, one of the essential factors for the poor outcome is the low blood perfusion of patients with vascular disease.

Neurosurgery, 1984 Aug, 15(2), 198 - 202
Ventriculoperitoneal shunts in high risk newborns weighing under 2000 grams: a clinical report; James HE et al.; Fifty-three low birth weight high risk newborns who developed progressive hydrocephalus despite a trial period of intermittent lumbar punctures underwent cribside ventriculoperitoneal shunt placement . They all weighed less than 2000 g at the time of shunting (mean, 1308.6 g +/- 398.2 SD) . The operative procedures were performed at a mean age of 31.5 days +/- 16.1 (SD) . There were no deaths in this series . During the nursery stay, 14 patients required operative revisions for obstruction . The most common problem was infection, which occurred in 13 (24.5%) after the primary intervention and in another 5 of the 14 (35.7%) patients who required revision . The overall infection rate/patient was 26.9% . Shunt removal and intensive antibiotic therapy cured the infection in all but 1 patient . Premature, low birth weight newborns may undergo ventriculoperitoneal shunting, but close follow-up for complications such as infection and shunt obstruction is always required.

Fundam Appl Toxicol, 1984 Aug, 4(4), 568 - 76
Nephrotoxic and ototoxic effects of hydroxygentamicin in cats; Slighter RG et al.; Hydroxygentamicin, an aminoglycoside antibiotic, was administered subcutaneously to cats in doses up to 160 mg base/kg daily for 10 to 13 weeks . Gentamicin and a vehicle solution were tested as positive and negative control, respectively; in one test netilmicin was also included for comparative purposes . Several parameters, including serum urea nitrogen, serum creatinine, organ/body weight ratios, serum and tissue concentrations of the antibiotics, and renal pathology, were determined to ascertain the nephrotoxic potential of the three aminoglycosides . In addition, observations for the onset of ataxia and impairment of righting reflex were made during the course of the studies to compare the vestibular ototoxic effects of the three antibiotics . Although serum urea nitrogen and serum creatinine values increased markedly in those cats which eventually died or were sacrificed moribund, these parameters in survivors were slightly but not significantly higher than controls . Serum concentrations of the drugs were proportional to the doses administered, but renal concentrations were approximately two and five times as high for netilmicin and gentamicin, respectively, as they were for equivalent doses of hydroxygentamicin . The morphological changes observed in the kidney of cats given 60 mg base/kg of hydroxygentamicin were slightly less than those seen in cats administered 10 mg base/kg of gentamicin; similarly, kidney changes in cats given netilmicin were observed approximately twice as frequently as they were in those receiving equivalent doses of hydroxygentamicin . The nephrotoxic effects of aminoglycoside antibiotics were directly related to renal drug concentration and not to serum concentration, which was a function of dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Biophys J, 1984 Aug, 46(2), 181 - 6
Random matrix theory in biological nuclear magnetic resonance spectroscopy; Lacelle S; The statistical theory of energy levels or random matrix theory is presented in the context of the analysis of chemical shifts of nuclear magnetic resonance (NMR) spectra of large biological systems . Distribution functions for the spacing between nearest-neighbor energy levels are discussed for uncorrelated, correlated, and random superposition of correlated energy levels . Application of this approach to the NMR spectra of a vitamin, an antibiotic, and a protein demonstrates the state of correlation of an ensemble of energy levels that characterizes each system . The detection of coherent and dissipative structures in proteins becomes feasible with this statistical spectroscopic technique.

Mutat Res, 1984 Aug, 140(4), 175 - 9
Sodium butyrate affects the cytotoxic and mutagenic response of V79 Chinese hamster cells to the genotoxic agents, daunorubicin and U.V . radiation; Pani B et al.; It has been suggested that conditions which lead to modifications in the chromatin structure could be responsible for an increased accessibility of DNA to genotoxic agents in eukaryotic cells . With this in mind, the cytotoxic and mutagenic activity of the anthracycline antibiotic, daunorubicin, and of UV radiation was assayed on V79 Chinese hamster cells pretreated or not with 5 mM sodium butyrate, an agent known to induce modifications in the chromatin structure: this treatment in fact proved to induce the hyperacetylation of the core histones, and moreover to enhance the cytotoxic response of the cells to both daunorubicin and UV radiation and the mutagenic response to daunorubicin.

Cardiovasc Res, 1984 Aug, 18(8), 497 - 501
Cell survival in canine aortic heart valves stored in nutrient medium; Mochtar B et al.; For transplantation of viable aortic valves a period of preservation will generally be needed . To maintain cell viability during this preservation period valves can be stored in nutrient medium after sterilisation in an antibiotic solution . To obtain quantitative data about the survival of aortic valve fibroblasts after preservation, we determined the number of viable fibroblasts in canine aortic valves after several weeks of preservation . The results shows that after storage of 1 week in nutrient medium cell survival is about 80%, after 2 weeks cell survival has declined substantially, while after 3 weeks survival is already unacceptably low . Storage for periods over 4 weeks results in almost completely non-viable aortic valves . These results show that only valves preserved for 1 to 2 weeks in nutrient medium can be considered as viable aortic valves.

Jpn J Antibiot, 1984 Aug, 37(8), 1470 - 87
{Pharmacological studies on a new cephamycin, MT-141 . (2) Its effect on preparations of neuromuscular junction, smooth muscle organs and gastro-intestinal system}; Yamaki Y et al.; The results for pharmacological experiments of MT-141 were as follows; Twitch tension of gastrocnemius muscle evoked by the stimulation of sciatic nerve was slightly reduced with 400 mg/kg MT-141 i.v . and upper doses . As the change was very small, however, it seems that MT-141 has no neuromuscular junction blocking action . Although MT-141 did not show any effects on most of isolated smooth muscle organs, only isolated tracheal muscle was somewhat relaxed with 10(-3) g/ml MT-141 . The spontaneous motility of smooth muscle in situ was temporarily increased with 800 mg/kg MT-141 i.v . and upper doses . Two hundred mg/kg MT-141 showed no effect on the value of blood sugar and functions of kidney and liver . Any hemolysis did not appear even in the highest dose of 200 mg/kg MT-141 used in this experiment . From the present results and previous report (Krebe, M . et al., Jap . J . Antibiotics, in press), it seems that MT-141 is promised to be a highly safe and useful antibiotic agent in clinical use.

J Antibiot (Tokyo), 1984 Aug, 37(8), 868 - 75
Biosynthesis of ketomycin; Takeda Y et al.; The antibiotic ketomycin is formed from shikimic acid via chorismic acid and prephenic acid . Phenylalanine and 2',5'-dihydrophenylalanine are not intermediates in the biosynthesis . Degradation of ketomycin derived from {1,6-14C}shikimic acid showed that prephenic acid is converted into ketomycin with stereospecific discrimination between the two enantiotopic edges of the ring, the pro-S-R edge giving rise to the C-2', C-3' side of the cyclohexene ring of ketomycin.

Transplantation, 1984 Aug, 38(2), 116 - 8
Bredinin treatment in clinical kidney allografting; Tajima A et al.; Bredinin, a new nucleoside antibiotic isolated from Eupenicillium brefeldianum, and steroids were used as immunosuppressive agents in 31 renal transplant patients; 17 of them received grafts from living-related donors and 14 from cadavers . The one-year graft survival rates were 100% in renal recipients from living donors and 69.2% in cadaver kidney recipients . There was no serious complication from the use of these immunosuppressive agents.

Thorac Cardiovasc Surg, 1984 Aug, 32(4), 250 - 2
Late results of valve xenograft conduits between the right ventricle and the pulmonary arteries in patients with pulmonary atresia and extreme tetralogy of Fallot; Yankah AC et al.; Between 1975 and 1982, valve xenograft conduits were used to establish continuity between the right ventricle and the pulmonary arteries in 28 patients between the ages of 3 to 39 years (mean 14.7 years) with 4 hospital deaths (14%) . The indications for operation were pulmonary atresia types I and II in 7, extreme tetralogy of Fallot with hypoplastic pulmonary artery and valvular ring in 10, secondary obliteration of the infundibulum following Waterston shunt in 4, pulmonary valve insufficiency after transannular right ventricular outflow tract patch in 5 and tetralogy of Fallot with anomalous coronary artery in 2 . Twenty-one patients (87%) between 9 and 41 years of age (mean 17.4 years) were available for follow-up 1/2 to 8 years after operation . The late death incidence during the follow-up period was 8% (2/24) . Postoperative cardiac catheterization, which included right and left ventriculogram and measurements of gradients, was performed in 14 patients 4 months to 6 years after operation . Four patients were in New York Heart Association (NYHA) class 1, 6 in class II and 4 in class III . The other 7 non-catheterized patients were in class II . There were resting peak systolic gradients of 15 to 35 mmHg in 4, 36 to 55 mmHg and more than 55 mmHg across the xenograft valve and the proximal anastomosis in 4 other patients . The right and left ventricular end-diastolic pressures (RVEDP, LVEDP) averaged 18 and 17.5 mmHg, respectively, in 3 patients . The mean ratio of PRV/PLV quotient in NYHA class I group was 0.3, in class II 0.45 to 0.7 and in class III greater than 0.7 (including 2 with residual VSD and pulmonary hypertension) . Late densitometric studies for assessing pulmonary valve competence revealed regurgitant fraction of up to 40% of the total stroke volume in the absence of a residual shunt 2 to 4 years after conduit implantation . Three children underwent uneventful surgical replacement of calcified xenograft conduit 1 1/2 to 4 1/2 years after surgery with antibiotic-sterilized valve allograft . Four other patients have residual ventricular septal defects (VSD), 2 of them underwent surgical reclosure while the other 2 patients with pulmonary hypertension still have their residual VSD open.(ABSTRACT TRUNCATED AT 400 WORDS)

J Biomol Struct Dyn, 1984 Aug, 2(1), 175 - 89
Intramolecular conformation of puromycin in solution as studied by proton magnetic resonance; Narula SS et al.; The intramolecular conformation of puromycin, a broad spectrum antibiotic, in solution has been investigated by proton magnetic resonance (PMR) spectroscopy . A comparison of the proton chemical shift and proton-proton coupling constant data of puromycin with puromycin aminonucleoside suggests that puromycin in solution exists as an equilibrium blend of extended and folded conformers . These folded conformers are the result of flexibility around the C alpha -C beta bond of the aminoacyl segment of puromycin . One of the folded conformers predicted by PMR is in excellent agreement with the x-ray data.

Antibiotiki, 1984 Aug, 29(8), 563 - 72
{DNA cloning in actinomycetes: the creation of vector systems}; Danilenko VN et al.; A new vector type was constructed on the basis of SLP 1.2 plasmid and the Kanr determinant of S . rimosus P3 . It was shown that the determinant was capable of amplifying in the chromosomes of S . rimosus during its improvement for increasing the level of resistance to kanamycin . Cloning of the Kanr determinant was performed on the Pst I-A fragment of the SLP 1.2 plasmid in S . lividans 66 . The Kanr determinant was expressed in the resulting hybrid plasmids, e . g . pSU 3, thus providing resistance of S . lividans to 20 micrograms/ml of kanamycin . As a result of repeated passages variants capable of growing in the presence of 50 000 micrograms/ml of the antibiotic were selected . The electrophoretic analysis of the total DNA fragments obtained after exposure to different endonucleases showed that they were identical to the respective fragments of the hybrid pSU 3 plasmid and amounted to approximately 40 per cent of the total DNA . The presence of the unique sites for the Bam HI, ClaI and SacI restriction endonucleases on the pSU 3 plasmid in an insignificant area and the relative stability (30-100 per cent) of the amplified variants allowed using it for cloning and amplification of DNA in Streptomyces . Plasmids were identified with the genetic and physical methods in 13 strains of the blue systematic group among the 72 strains studied . A multicopy plasmid with a molecular weight of 5.6 MD designated as pSB 24.1 was identified in the family of the plasmids of S . cyanogenus . The deletion and insertion variants of the pSB 24.1 plasmid were obtained . The comparative study of the properties of these plasmids revealed the areas insignificant for replication and maintenance of the pSB 24.1 plasmid and the area determining the Ltz+-phenotype . It was suggested that formation of the deletion and insertion variants of the pSB 24.1 plasmid was provided by the site specific recombination mechanisms . The presence of the unique sites for a number of the restriction endonucleases located in the insignificant area, the presence of the selective marker and the high transformation frequency allowed one to consider the multicopy pSB 24.1 plasmid an acceptable vector for cloning of DNA in Streptomyces.

Biochem Biophys Res Commun, 1984 Jul 31, 122(2), 748 - 54
Inhibition of peptidyltransferase and possible mode of action of a dipeptidyl chloramphenicol analog; McFarlan SC et al.; A dipeptidyl chloramphenicol analog, D-threo-2-(L-phenylalanylglycyl)amino-3-p-nitrophenyl-1,3- propanediol, has been prepared and examined as an inhibitor of ribosomal peptidyltransferase . The analog is a more effective inhibitor of poly (U,C) directed protein biosynthesis in an Escherichia coli cell-free system than chloramphenicol and shows inhibitory activity equal to the parent antibiotic in the transpeptidation reaction . These results and the common structural features of puromycin and this compound suggest a model for the binding modes of chloramphenicol and chloramphenicol analogs . This proposal invokes four major binding pockets at the A-site of the peptidyltransferase center.

FEBS Lett, 1984 Jul 23, 173(1), 5 - 8
Detection of a bromoperoxidase in Streptomyces phaeochromogenes; van Pee KH et al.; A bromoperoxidase could be detected after fractionation in the chloramphenicol producing actinomycete, Streptomyces phaeochromogenes . This enzyme is capable of catalyzing the bromination of the antifungal antibiotic pyrrolnitrin {3-chloro-4-(2-nitro-3-chlorophenyl)pyrrole} in the 2-position of the pyrrole ring . The enzyme had a pH optimum of 5.0 . This procaryotic bromoperoxidase requires the presence of H2O2 and can also brominate monochlorodimedone, but cannot catalyze chlorination . This enzyme is the first haloperoxidase described from procaryotic sources.

Med J Aust, 1984 Jul 21, 141(2), 114 - 5
Mycotic aneurysm of the small bowel presenting as gastrointestinal haemorrhage; Wilson JW et al.; Since the advent of modern antibiotic therapy and active surgical treatment of bacterial endocarditis, septic embolization of the systemic circulation is rarely seen . An unusual presentation of a mycotic aneurysm with gastrointestinal haemorrhage in a patient with non-Hodgkin's lymphoma and aortic valvular endocarditis which had been managed by aortic valve replacement six weeks before the haemorrhage occurred is reported.

Life Sci, 1984 Jul 16, 35(3), 267 - 76
Dual calcium-dependent protein phosphorylation systems in pancreas and their differential regulation by polymyxin B1; Wrenn RW et al.; Both phospholipid/calcium (PL/Ca2+) activated and calmodulin/Ca2+ (CaM/Ca2+)activated protein kinase systems were found in rat pancreatic extracts treated with Sephadex G-25 . At least four substrate proteins for PL/Ca2+-activated kinase and one for a CaM/Ca2+-activated kinase were noted . Polymyxin B, an amphipathic antibiotic, was over 100-fold more potent as an inhibitor of PL/Ca2+-dependent protein phosphorylation than of the CaM/Ca2+-dependent system (Ki = app . 7 microM v . 950 microM) . Fluphenazine inhibited both PL/Ca2+- and CaM/Ca2+-dependent protein kinases with equal potency, as did dibucaine . Inhibition by polymyxin B of PL/Ca2+-dependent phosphorylation could be overcome by increased amounts of phosphatidylserine . Low concentrations (10(-5)M) of polymyxin B completely inhibited carbachol-stimulated amylase release from intact pancreatic acini . These results indicate that polymyxin B may be useful in delineating the relative roles of PL/Ca2+-dependent and CaM/Ca2+-dependent protein phosphorylation in biological systems and suggest a potential role for the PL/Ca2+-activated kinase in regulation of pancreatic exocrine function.

Am J Ophthalmol, 1984 Jul 15, 98(1), 11 - 6
Clinical evaluation of trimethoprim-containing ophthalmic solutions in humans; Lamberts DW et al.; We studied trimethoprim in combination with sulfacetamide and polymyxin B and also in combination with polymyxin B alone (without the sulfacetamide) to determine the efficacy and safety of these new antibiotic combinations in the eyes of patients with bacterial conjunctivitis or blepharitis . Patients were selected for the study if they showed at least three of the following criteria: (1) symptoms of a surface ocular infection; (2) a purulent discharge; (3) a polymorphonuclear neutrophilic response on Giemsa stain; (4) a history of recent exposure to an infected individual; (5) a history of an inadequately treated surface bacterial infection . Trimethoprim-sulfacetamide-polymyxin B and polymyxin B-neomycin-gramicidin (Neosporin, the control) eliminated bacteria from the eyes of patients with conjunctivitis or blepharitis with equal effectiveness . There was no loss of effectiveness when trimethoprim-polymyxin B was compared with trimethoprim-sulfacetamide-polymyxin B, suggesting that the sulfacetamide was not a necessary component . The combination antibiotic containing trimethoprim and polymyxin B appears to be an effective topical antibiotic solution for the treatment of ocular surface infections.

Biochim Biophys Acta, 1984 Jul 11, 774(1), 119 - 26
Increased efficiency of the outer membrane PhoE protein pore in Escherichia coli K-12 mutants with heptose-deficient lipopolysaccharide; Korteland J et al.; The pore properties of PhoE protein channels in the outer membrane of a lipoprotein-deficient mutant and in a mutant with heptose-deficient lipopolysaccharide were investigated . The absence of lipoprotein neither affects the rate of permeation of glucose 6-phosphate or of the beta-lactam antibiotic cephsulodin through the PhoE pore nor the inhibition of cephsulodin permeation by polyphosphate . In contrast, heptose deficiency results in a 6- to 8-fold increase in the rates of permeation of glucose 6-phosphate and cephsulodin . Possible explanations for these data are discussed . It is argued that the lipopolysaccharide structure synthesized under phosphate limitation may be similar to that of the heptoseless mutant and hence that not only the structure of the PhoE protein pore but also the structure of the lipopolysaccharide may promote the uptake of Pi and Pi-containing solutes under phosphate limitation.

Eur J Biochem, 1984 Jul 2, 142(1), 113 - 9
A study of the structure and dynamics of complexes between polymyxin B and phosphatidylglycerol in monolayers by fluorescence; Theretz A et al.; Interactions between the antibiotic polymyxin B and monolayers of dipalmitoylglycerophosphoglycerol have been reinvestigated through a study of the structure and dynamics of the complexes by means of an interface fluorimeter of our fabrication . A fluorescence technique has been developed where the use of linearly polarized incident beams gives the simultaneous determination of the orientation and the lateral diffusion rate of a fluorescent probe inserted in the film . The present investigation was carried out with 12-(9-anthroyloxy)-stearic acid, a fluorescent compound which forms non-fluorescent photodimers upon illumination . Orientation of the probe was studied by computing the ratio of the two dimerization constants KD and the ratio of the fluorescence intensities obtained with crossed linearly polarized incident lights . The lateral diffusion rate of the probe was obtained by measuring fluorescence recovery after photobleaching (photodimerization) of the probe . Control experiments, carried out with dimyristoylglycerophosphocholine, a lipid which does not interact with polymyxin B, show that the antibiotic does not significantly modify the behaviour of the probe . Both in terms of orientation and dynamics, with respect to dipalmitoylglycerophosphoglycerol, when the antibiotic is present in the subphase (1 microM, saturating conditions), data indicate that the lipid remains in a liquid-expanded state . This is true even at a high surface pressure (pi approximately equal to 37 mN X m-1), above the apparent 'transition' which can be observed at 30-35 mN X m-1 on its compression isotherm . Computation of the contribution of polymyxin B to the film expansion to the conclusion that this 'transition' would be a structural transition between two models of interaction: one, below the 'transition', where the polypeptide ring penetrates between the film-forming lipid molecules and another one, above the 'transition', were the antibiotic is adsorbed at the lipid-water interface with only its hydrocarbon chain penetrating the film.

Drug Intell Clin Pharm, 1984 Jul-Aug, 18(7-8), 596 - 8
Hypomagnesemia associated with gentamicin therapy; Nanji AA et al.; Two patients developed symptomatic hypomagnesemia most likely secondary to gentamicin therapy . Both patients were on regular doses of the antibiotic and had hypokalemia and hypocalcemia secondary to hypomagnesemia . Mechanisms postulated for the occurrence of hypomagnesemia secondary to gentamicin therapy include drug-induced hyperaldosteronism and tubular toxicity . Patients on gentamicin therapy should have serum magnesium, calcium, and potassium levels monitored routinely.

Br J Pharmacol, 1984 Jul, 82(3), 673 - 7
Effects of neomycin on galactose absorption across rat jejunum; Debnam ES et al.; The effects of neomycin sulphate on galactose absorption have been studied using in vivo and in vitro preparations of rat small intestine . Neomycin (10(-3)M) produced an increase in the maximum transport capacity (Jmax) for the active component of absorption in vivo . The apparent Kt for absorption was unaffected . The antibiotic caused a dose-dependent increase in the potential difference across the mucosal membrane (Vm) measured in vitro, a maximal effect being seen at a concentration of 10(-4)M . Furthermore, the magnitude of the depolarization induced by the addition of galactose (4 mM) to the mucosal fluid was enhanced by neomycin (10(-4)M) . Phlorhizin (10(-4)M) abolished the galactose-induced depolarization in both the absence and presence of the antibiotic . It is concluded that neomycin increases the electrical driving force for Na+ during Na+-coupled galactose entry into the enterocyte.

Am J Obstet Gynecol, 1984 Jul 1, 149(5), 492 - 5
Course and treatment of milk stasis, noninfectious inflammation of the breast, and infectious mastitis in nursing women; Thomsen AC et al.; In nursing women with inflammatory symptoms of the breast, it has been possible on the basis of leukocyte counts of the milk and quantitative cultivation for bacteria to classify these cases into milk stasis (counts of less than 10(6) leukocytes and less than 10(3) bacteria per milliliter of milk), noninfectious inflammation (counts of greater than 10(6) leukocytes and less than 10(3) bacteria), and infectious mastitis (counts of greater than 10(6) leukocytes and greater than 10(3) bacteria) . In the present study the duration and outcome of these cases were observed, and those without intervention were compared to those with treatment that consisted of systematic and intensive emptying of the breast, supplemented in some cases by antibiotic therapy as directed by susceptibility tests of the bacteria . The course of milk stasis was of short duration and the outcome was good independent of treatment . In cases of noninfectious inflammation the symptoms persisted for several days without treatment, and half of the patients developed infectious mastitis . Emptying of the breast resulted in a significant decrease in the duration of symptoms and a significantly improved outcome . Infectious mastitis without treatment was followed by a good result in only 15% of the cases, and 11% developed abscesses . Emptying of the breast increased the rate of a good outcome to 50% and significantly decreased the duration of symptoms . The addition of antibiotic therapy resulted in a good outcome in 96% of the cases and a further significant reduction of the persistence of symptoms.

Laryngoscope, 1984 Jul, 94(7), 966 - 8
Cervical ankylosing hyperostosis and airway obstruction; Hassard AD; Forestier's disease, or ankylosing hyperostosis of the cervical spine, has been described to cause dysphagia, foreign body sensation, and aspiration . We report two patients with ankylosing hyperostosis producing ulceration of the posterior plate of the cricoid cartilage, inflammatory edema, and secondary bilateral vocal cord paralysis with airway obstruction . This disease initially produces minimal dysphagia when the primary location of the osteophyte is just above and posterior to the cricoid, then, progressive airway obstruction . The pathogenesis is infection superimposed on ulceration of the cricoid produced by laryngeal movement over a large, sharp osteophyte . Management included tracheostomy for airway management, endoscopy to rule out malignancy, intravenous antibiotic therapy, and surgical excision of the osteophyte.

Laryngoscope, 1984 Jul, 94(7), 907 - 11
Changing concepts in the management of otitic intracranial infection: use of computerized axial tomography in early detection and monitoring of cerebritis; Freeman J; The pathogenesis and course of intracranial inflammatory disorders of otitic origin have been studied extensively in the past by clinical, surgical, and morbid means . The recent contribution by CT scanning cannot be overestimated as a modality for identification of the pathologic process . Its use for early detection and monitoring of a clinically suspected intracranial complication of otitic suppurative disease is documented for the first time in this report . Cerebritis or encephalitis as the early manifestation of impending brain dissolution can be identified and followed during specific antibiotic therapy . The proper timing for surgery to remove the otitic focus is enhanced . A review of the literature and a case report illustrate this contribution.

J Neuropathol Exp Neurol, 1984 Jul, 43(4), 384 - 94
The evolution of cellular degeneration in dorsal root ganglia exposed to doxorubicin in tissue culture; Zagoren JC et al.; Doxorubicin (Adriamycin) is a drug having both antibiotic and antimitotic properties . It intercalates between base pairs of DNA causing breaks in the helical strands . It is widely used as a cancer chemotherapeutic agent but is limited in use by a dose-related cardiomyopathy and necrosis of peripheral ganglia . This study of cultured mouse spinal cord and dorsal root ganglia examined the sequential pathological changes of living tissue by light and fluorescence microscopy and of fixed tissue by electron microscopy . Fluorescence microscopy showed that doxorubicin has rapid access to ganglia cells and preferentially binds to the nucleus and nucleolus . Pathological changes of the peripheral neurons include clumping of nuclear chromatin, relocation of the indented nucleus to an eccentric position, occasional loss of the nuclear envelope, dissociation of the nucleolus into the pars granulosa and the pars fibrosa, accumulation of inclusion bodies in the cytoplasm, swollen cisternae and a loss of Nissl substance . Axons display changes in localization of organelles prior to undergoing proximal Wallerian-like degeneration . Schwann cells occasionally display clumped nuclear chromatin . Some satellite cells undergo necrosis . These findings are dose- and time-related and essentially duplicate those previously reported in animal studies . Thus, the in vitro model may provide a useful tool for ascertaining the sequence of events occurring in sensory neuronopathy.

J Adolesc Health Care, 1984 Jul, 5(3), 207 - 9
Epiglottitis in the adolescent; Lande AE; Acute epiglottitis is rare in adolescents . Respiratory compromise may not occur early . Physicians should consider this diagnosis in their adolescent patients who complain of pain and dysphagia, with or without visible pharyngitis . Airway maintenance is paramount . The antibiotic used should include coverage for Hemophilus influenzae, type B . The case presented here illustrates these points.

Exp Cell Res, 1984 Jul, 153(1), 91 - 8
Compactin (ML-236B) reduces the content of filipin-cholesterol complexes in the plasma membrane of chronic lymphocytic leukemia cells; Madden EA et al.; The polyene antibiotic filipin was used to visualize the presence and distribution of cholesterol in the plasma membrane of glutaraldehyde-fixed human chronic lymphocytic leukemia (CLL) cells . Both compactin (ML-236B), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and 25-hydroxycholesterol reduced the content of filipin-cholesterol complexes in the plasma membrane of CLL cells grown in media supplemented with either 15% delipidized horse serum or 15% normal (whole) horse serum . The reduction due to compactin was reversed by the concomitant addition of mevalonolactone . The ability of compactin to reduce the relative cholesterol content (as judged by filipin labeling) in CLL cells grown in lipoprotein-containing (normal) serum suggest that either CLL cells are different from other cells in that they predominantly utilize endogenously synthesized cholesterol for incorporation into the plasma membrane, or that a separate pool of endogenously synthesized cholesterol provides cholesterol for the plasma membrane.

Clin Immunol Immunopathol, 1984 Jul, 32(1), 90 - 100
Ia antigen expression is increased on tunicamycin-resistant human B-lymphoid cells; Glassy MC et al.; Cultured human B-lymphoid cells WIL-2 were mutated with ethylmethane sulfonate and selected for resistance to tunicamycin, an antibiotic that selectively inhibits N-linked glycosylation . Ultrastructural analysis of five isolated tunicamycin-resistant mutants (TMR) showed changes in surface microvilli, dilation of the endoplasmic reticulum, and an increase in surface myelin figures . Cytofluorometric analysis of TMR cells incubated with anti-HLA monoclonal antibodies showed a normal density of HLA-A, B antigens and an increased density of Ia antigens . The properties of these TMR mutants have remained stable for at least 18 months . These TMR cells may serve as a useful model to study the biochemical events in the processing and expression of Ia antigens.

Neurosurgery, 1984 Jul, 15(1), 43 - 9
Evolution and resolution of intracranial bacterial (mycotic) aneurysms; Morawetz RB et al.; Surgical therapy of bacterial intracranial aneurysms may prove difficult when multiple aneurysms are present or lesions are proximally located . Two patients underwent operation for bacterial intracranial aneurysms without resolution of their problems, in one case because of the involvement of a proximal branch of a dominant middle cerebral artery and in the other because of the presence of multiple bilateral aneurysms . Both patients underwent multiple angiographic evaluations during the course of treatment with documentation of complete resolution of their aneurysms over many months . The time course of the evolution and resolution of the bacterial intracranial aneurysms identified in the two patients is described, and antibiotic therapy and cardiac surgery are discussed.

Ann Acad Med Singapore, 1984 Jul, 13(3), 548 - 51
Infective endocarditis in Singapore: a six year survey; Sin FL et al.; Much has been written about the changing clinical spectrum of infective endocarditis . However our survey shows that the classical text book descriptions still hold good . The majority of our patients were young with 79% either 30 years or below . Fever was present in 93%, splenomegaly in 50% and cerebral embolism in 43% of our patients . Twelve patients had valvular heart disease and 2 patients had a ventricular septal defect . Eleven out of 14 patients had a positive blood culture . Echocardiography detected definite or probable vegetations in 66% of the examinations . Five patients responded satisfactorily to antibiotic therapy, 2 patients discharged themselves from hospital against medical advice, and 4 patients underwent successful cardiac surgery . Three patients died during medical therapy.

Jikken Dobutsu, 1984 Jul, 33(3), 345 - 9
Assessment of mouse strain on bacterial translocation from the gastrointestinal tract; Maejima K et al.; The translocation of indigenous bacteria from the gastrointestinal tract to the mesenteric lymphnodes was compared in ten strains of mice . Indigenous Escherichia coli were cultured from the mesenteric lymphnodes of only two of the six mouse strains examined . Thus, spontaneous translocation of indigenous enteric bacteria across the intestinal barrier did not occur to any significant extent in any of the mouse strains examined . Since bacterial overgrowth in the gastrointestinal tract promotes bacterial translocation, bacterial translocation was tested in ten mouse strains including B10 series after antibiotic-decontaminated and subsequent colonization with streptomycin-resistant E . coli C25 . E . coli C25 populated the ceca of the mice at levels of 10(8) to 10(9) per gram and translocated to 90-100% of the mesenteric lymphnodes with mean of 10(1.13) to 10(1.86) per mesenteric lymphnode . However, there were no significant differences between mouse strains as to the translocation incidence or the numbers of viable E . coli C25 per mesenteric lymphnode . Thus, genetic differences between mouse strains did not influence bacterial translocation from the gastrointestinal tract to the mesenteric lymphnodes.

J Vasc Surg, 1984 Jul, 1(4), 579 - 81
Treatment of Aspergillus infection of the proximal aortic prosthetic graft with associated vertebral osteomyelitis; Anderson J et al.; This is a case report of an unusual vascular graft infection involving an invasive Aspergillus species with associated vertebral osteomyelitis . Successful treatment was obtained by graft incision, extra-anatomic bypass, and prolonged antibiotic therapy . To our knowledge this is the first successful treatment of invasive Aspergillus of an aortic prosthetic graft.

Antibiotiki, 1984 Jul, 29(7), 516 - 9
{Action of reumycin on the blood system in an experiment}; Svinogeeva TP et al.; The effect of reumycin, an antitumor antibiotic on the peripheral circulatory system and bone marrow was studied on albino rats . The drug was injected intraperitoneally in a dose of 25 mg/kg daily for 30 days . It was shown that reumycin had a comparatively low toxic effect on the peripheral circulatory system and hemopoiesis . It induced the signs of transitory anemia and did not suppress the regenerative capacity of the bone marrow . After the drug repeated use there was an increase in the platelet count and in the rate of blood coagulation . These signs vanished a month after the end of the treatment course.

Antibiotiki, 1984 Jul, 29(7), 501 - 6
{Effect of a modifying factor on the sensitivity of Crithidia oncopelti to levorin}; Sukhareva-Nemakova NN et al.; The paper deals with possible discovery of ways for increasing sensitivity of trypanosomides to polyenic antibiotics . The following substances were tested: sodium pyruvate and acetate, calcium salts, ascorbic acid and 1-valine . The total number of the cells and the number of the viable cells in the culture and their morphological characteristics were used as the criteria for estimation of the C . oncopelti sensitivity . It was shown that sodium acetate most actively modified the levorin effect on C . oncopelti . Its addition in a concentration of 40 mg/ml to the cultivation medium with levorin in a concentration of 1 microgram/ml induced a trypanocidal effect . With the use of levorin alone such an effect was observed when the antibiotic was used in a concentration of 10 micrograms/ml . The growth rate of the protozoon was decreased by 60-80 per cent as compared to the control . The number of the viable cells was lowered 4 times . The morphology of the culture markedly changed . This indicates that the presence of sodium acetate as a modifier in the culture medium allowed one to decrease 10 times the dose of levorin and to preserve the trypanocidal effect.

Antimicrob Agents Chemother, 1984 Jul, 26(1), 112 - 4
Activity of herbicolin A against Mycoplasma, Acholeplasma, Ureaplasma, and Spiroplasma species; Freundt EA et al.; Herbicolin A, a novel acyl peptide antibiotic, inhibits the growth of the sterol-requiring Mycoplasma, Ureaplasma, and Spiroplasma species, with MICs varying from 1.5 to 100 micrograms/ml . With the exception of Acholeplasma modicum, all of the non-sterol-requiring species of the family Acholeplasmataceae were totally resistant to herbicolin A when tested on serum-containing medium but were inhibited to some extent on medium devoid of serum and any other source of sterol or fatty acids.

Am J Trop Med Hyg, 1984 Jul, 33(4), 637 - 44
Penicilliosis marneffei in Thailand: report of five human cases; Jayanetra P et al.; The first two cases of Penicillium marneffei infection in humans were reported in 1959 and 1973 . There had been no additional clinical reports of penicilliosis marneffei, until the five new cases of human infection described in this paper, the first from Thailand . The patients, three of whom died, came from various parts of the country . Their common clinical manifestations were fever and generalized lymphadenopathy, with multiple soft tissue, bone, joint and pulmonary involvement . Pericarditis with effusion was also seen . The diagnosis was established by isolating and identifying a dimorphic Penicillium species that produced a soluble red pigment in its mycelial form . The histopathologic features of the lymph nodes and bone marrow were similar to those of histoplasmosis capsulati . However, the yeast-like tissue form of P . marneffei divides by fission; that of Histoplasma capsulatum by budding . Treatment with amphotericin B was effective when this antifungal antibiotic was administered early in the course of the disease.

Rev Infect Dis, 1984 Jul-Aug, 6(4), 497 - 500
A two-step mechanism for the interaction of Re lipopolysaccharide with erythrocyte membranes; Carr C Jr et al.; In this report, a unique model system that allows the investigation of the interaction of lipopolysaccharide (LPS) with erythrocyte membranes is described . Rabbit red blood cells exposed to S . minnesota (Re mutant) R595 LPS were rendered sensitive to the cationic antibiotic polymyxin B in a manner independent of the temperature of incubation of erythrocytes with LPS (subsequent addition of polymyxin B induced hemolysis of erythrocytes sensitized with LPS) . Following sensitization of red blood cells with R595 LPS, a time-dependent decrease in susceptibility of the cells to polymyxin B-mediated hemolysis occurred, which was shown not to be the result of dissociation of LPS from rabbit erythrocytes . The demonstration that the decrease in sensitivity of red blood cells to polymyxin B was dependent on the temperature of incubation of LPS with red blood cells is not inconsistent with the proposal that the decrease in sensitivity is attributable to a hydrophobic rearrangement of lipid-rich R595 LPS within the lipid bilayer of the erythrocyte membrane . The importance of this putative rearrangement of LPS within cell membrane in cellular triggering of LPS is unknown.

Cytometry, 1984 Jul, 5(4), 348 - 54
7-Amino-actinomycin D as a specific fluorophore for DNA content analysis by laser flow cytometry; Zelenin AV et al.; A technique for DNA amount determination by flow cytometry based on the use of 7-amino-actinomycin D (7-amino-AMD), a fluorescent analogue of antibiotic actinomycin has been investigated, and a particular staining procedure has been developed . The procedure includes short fixation in 70% ethanol and staining for 20 min in 10(-5)M solution of 7-amino-AMD at pH7 . The results of DNA content measurements are very reproducible . The histograms obtained have a coefficient of variation less than 3% . The absorption maximum of the complex of 7-amino-AMD with DNA is situated in the green spectrum region, making this stain particularly suitable for argon laser flow cytometry.

Clin Allergy, 1984 Jul, 14(4), 355 - 61
Bronchial asthma due to spiramycin and adipic acid; Moscato G et al.; Two cases of bronchial asthma due to spiramycin in workers of a pharmaceutical factory are reported . The subjects complained of cough, breathlessness and symptoms of asthma at work when coming into contact with spiramycin's powder . The symptoms cleared when away from work for more than 3 or 4 days . Inhalation challenge tests by aerosolization of solutions of spiramycin reproduced asthmatic reactions dual in type in both patients, the immediate component of the response has not been previously described for this antibiotic . Furthermore, one of the patients developed an immediate asthmatic reaction also after inhalation of a solution of adipic acid, and additive to bind spiramycin and diminish its irritant action . The reaction was obtained at a non-irritant concentration of the acid, was reproducible and inhibited by previous administration of sodium cromoglycate: this finding and the failure to elicit the reaction in the other patient suggest a hypersensitivity reaction to this substance.

Am J Hosp Pharm, 1984 Jul, 41(7), 1338 - 42
Progressive pharmaceutical services in a small community hospital; Chase PA; The pharmaceutical services in an 86-bed community hospital in rural Maine are described . With a staff of two full-time pharmacists, one hospital pharmacy resident, and 2.6 full-time equivalent technicians, the pharmacy department operates a 24-hour unit dose drug distribution system with complete i.v . admixture services . In addition, the department supervises nurses on medication administration and i.v . therapy teams . Clinical pharmacy services include patient-education programs, protocols giving pharmacists responsibility for initiating and monitoring specific drug therapies when authorized by a physician, and concurrent antibiotic review . The department publishes a bimonthly newsletter for physicians and nurses and a quarterly newsletter for hospital employees and patients; it also conducts continuing-education programs for nurses . By maintaining a delicate balance between creativity and practicality, pharmacists in small hospitals can develop progressive services.

Clin Sci (Lond), 1984 Jul, 67(1), 117 - 20
Inhibition of jejunal water and electrolyte absorption by therapeutic doses of clindamycin in man; Spiller RC et al.; A steady-state perfusion technique has been used in vivo in normal subjects to show that at concentrations occurring during therapeutic use (500 mg/1, 1.1 mmol/l) the antibiotic clindamycin reversibly inhibits bicarbonate-stimulated water and electrolyte absorption from the human jejunum . Lactose-stimulated water and electrolyte absorption was not affected by the addition of clindamycin at the same concentration . Clindamycin-induced malabsorption of water and electrolytes may contribute significantly to the diarrhoea that occurs during clindamycin therapy in the absence of pseudomembranous colitis.

J Cell Biol, 1984 Jul, 99(1 Pt 1), 315 - 9
Detection of membrane cholesterol by filipin in isolated rat liver coated vesicles is dependent upon removal of the clathrin coat; Steer CJ et al.; We investigated the cholesterol content of highly purified populations of coated vesicles from rat liver by biochemical quantitation and by cytochemical electron microscopy using the polyene antibiotic filipin . Failure of this reagent to elicit its typical response for a cholesterol-containing membrane, i.e., a characteristically corrugated or rippled appearance by thin section analysis, had led to the hypothesis (Montesano, R., A . Perrelet, P . Vassalli, and L . Orci, 1979, Proc . Natl . Acad . Sci . USA., 76:6391-6395) that cholesterol is specifically excluded from the plasma membrane domains associated with coated pit regions . The present electron microscopic results showed that although the response of coated vesicle membranes to filipin was also negative, uncoated vesicles whose clathrin coats had been removed in vitro exhibited a strong filipin-positive response . Quantitated biochemically, the cholesterol-to-phospholipid ratio of the coated vesicles was found to be indistinguishable from that of control preparations of plasma membranes isolated from rat liver . Taken together, the results indicate that the filipin-negative response of coated vesicles (and probably also that of coated pits) is due not to abnormally low cholesterol content, but rather to the stabilizing influence of their enveloping clathrin coats which inhibit the characteristic structural expression of the filipin-cholesterol complexes.

Drug Intell Clin Pharm, 1984 Jul-Aug, 18(7-8), 609 - 11
Acute pneumonitis associated with MOPP chemotherapy of Hodgkin's disease; Cersosimo RJ et al.; A case of a 69-year-old man admitted with procarbazine pneumonitis and a review of the literature are presented . The patient completed a second course of MOPP chemotherapy for Hodgkin's disease three days before admission . He presented with a recent onset of fever, chills, anorexia, and malaise . Chest radiography indicated diffuse bilateral interstitial pneumonitis, and pulmonary function studies revealed restrictive lung disease . Attempts to identify an infectious etiology, including open lung biopsy, were negative, and empirical antibiotic therapy was ineffective . The diagnosis was drug-induced hypersensitivity reaction, most likely due to procarbazine . Corticosteroid therapy was instituted with gradual improvement . Six other cases of pneumonitis associated with procarbazine therapy are briefly reviewed, and the use of pulmonary function tests to identify the type and degree of injury and monitor therapy is discussed.

Antibiotiki, 1984 Jul, 29(7), 513 - 6
{Action of the alkyl derivatives of amphotericin B on the conductivity of bilayer lipid membranes}; Kasumov KhM et al.; Amphotericin B alkyl derivatives increased conductivity of bilayer membranes by formation of channels in them . The properties of such channels were studied . A new method for determination of the polyene antibiotic toxicity is described . The method is based on measurement of the constant of the relaxation time on the antibiotic removal from the membrane solution . It was shown that the amphotericin B alkyl derivatives had very low toxicity for the mammalian cells and were highly toxic for the fungal cells . These antibiotics may be used as new effective antifungal compounds.

Resuscitation, 1984 Jul, 12(2), 141 - 6
Management of crush syndrome; Michaelson M et al.; Our experience in treating seven patients with severe crush injury of the lower limbs is described . They were brought to hospital 12 h after rescue and had no treatment until then . All seven developed acute renal failure due to myoglobinuria and dehydration . Five were anuric and three non-oliguric . All developed severe sepsis and two had also acute respiratory failure . No bleeding tendency was observed . They were treated along the following lines: early extensive fasciotomy and removal of dead tissues; early fluid challenge; early peritoneal dialysis and/or hemodialysis; high caloric, high protein nutrition; vigorous antibiotic therapy when infection was evident . There were no deaths in our patients . Our management and results are discussed and compared with those in the literature.

J Gen Microbiol, 1984 Jul, 130 ( Pt 7), 1603 - 12
Genome size and complexity in Azotobacter chroococcum; Robson RL et al.; All of eight strains of Azotobacter chroococcum examined contained between two and six plasmids ranging from 7 to more than 200 MDal in size . Strain MCC-1, a derivative of NCIMB 8003, was cured of various of the four largest of its five plasmids and the phenotypes of the strains compared . all fixed nitrogen and exhibited uptake hydrogenase activity . No differences were observed in carbon source utilization or antibiotic, heavy metal or UV resistance . The genome sizes of two strains of A . chroococcum were determined by two-dimensional electrophoresis . Strain CW8, an isolate from local soil containing two small plasmids of 6 and 6.5 MDAl contained unique DNA sequences equivalent to 1.78 x 10(6) (+/- 20%) bp (1.2 x 10(9) Dal) . In strain MDC-1, a derivative of MCC-1, containing a 190 MDal and 7 MDal plasmid, the genome size was 1.94 x 10(6) (+/- 20%) bp . In exponential batch cultures, both contained 20 to 25 genome equivalents per cell . MCD-1 exhibited complex UV kill kinetics with a marked plateau of resistance; CW8 showed a simple response inconsistent with the possibility of organization of its DNA into identical chromosome copies capable of independent segregation.

Proc Natl Acad Sci U S A, 1984 Jul, 81(14), 4500 - 4
Distribution of DNA insertion element IS5 in natural isolates of Escherichia coli; Green L et al.; DNA from Escherichia coli strains in a reference collection of 72 recent natural isolates (ECOR strains) and 25 natural isolates from the "pre-antibiotic" period 1930-1940 (Murray strains) were studied to determine the genomic abundance of insertion element IS5 and the size of genomic restriction fragments carrying sequences homologous to IS5 . Among the ECOR strains, nearly two-thirds lack DNA sequences that hybridize with IS5, and one-half of the remainder have only one copy . Among strains in which IS5 is present, extensive variation in the size of IS5-bearing restriction fragments occurs, in many cases allowing distinction among strains that are judged to be nearly identical in genotype because of the identical electrophoretic mobility of the enzyme coded by each of 11 chromosomal loci . Among the Murray strains in which IS5 is present, the average number of elements per strain is larger, but not markedly so, than among recent isolates . Comparison between duplicate strains in the Murray collection suggests that the rate of accumulation of IS5 elements in prolonged storage in stab tubes corresponds to an apparent probability of transposition of approximately 0.008 +/- 0.002 per IS5 element per year . Because of the extensive genetic variation among strains, insertion elements such as IS5 would seem to be convenient genetic markers with which to detect recent common ancestry among strains.

Wien Med Wochenschr, 1984 Jun 30, 134(12), 292 - 4
{Etiology of cerebral infarcts caused by emboli--subacute bacterial endocarditis}; Reisecker F et al.; Bacterial endocarditis is a rare cause of brain infarction . Prediposing factors are frequently valvular defects secondary to rheumatic conditions . A slowly progressive course and atypical symptoms of the disease can mask the condition to such an extent that the correct diagnosis is obtained only through the work up of secondary embolic complications . Modern antibiotic combinations therapy yields a cure in 98% of the cases . The problems obtaining the diagnosis and the course of the disease with antibiotic therapy will be demonstrated in a case of embolic brain infarction secondary to bacterial endocarditis.

Boll Soc Ital Biol Sper, 1984 Jun 30, 60(6), 1229 - 31
{Effect of amphotericin B on phagocytosis and intracellular killing of E . coli by rat liver perfused in vitro: preliminary results}; Andreana A et al.; Using isolated and perfused rat livers we found an inhibitory effect on intracellular killing of hepatic macrophages versus E . coli, in presence of therapeutic levels of amphotericin B (5 micrograms/ml) . Since an interference of this antibiotic with phagocytic functions of human neutrophils has also been reported, we suggest that amphotericin B may exert a toxic effect on intraphagocytic microbicidal function, possibly by an interaction with membrane sterols.

Nucleic Acids Res, 1984 Jun 25, 12(12), 4865 - 79
Sequence-specific binding of echinomycin to DNA: evidence for conformational changes affecting flanking sequences; Low CM et al.; The technique of DNAase I footprinting has been used to investigate preferred binding sites for echinomycin on a 160-base-pair DNA fragment from E . coli containing the tyr T promoter sequence . Six binding sites have been precisely located in the sequence; a seventh has been partially identified . The minimum site-size is six base pairs . All the binding sites contain the dinucleotide sequence CpG but no other regularities can be discerned . When the protected regions on each complementary strand are compared it is evident that they are staggered by 2-3 base-pairs towards the 3' end at each site . Footprinting with DNAase II reports a similar, though less precise, pattern of protection . Cutting by both enzymes is markedly enhanced at AT-rich regions flanking the antibiotic-binding sites . This increased susceptibility to nuclease attack can be attributed to an altered helix conformation in the vicinity of the bis-intercalated echinomycin molecule . It seems that certain sequences, mainly runs of A or runs of T, switch from a nuclease-resistant to a nuclease-sensitive form when echinomycin binds nearby.

Minerva Med, 1984 Jun 8, 75(24), 1445 - 9
{Supportive therapy in brain tumors in children}; Bianchi E et al.; Recent advances in brain tumors therapy in infancy may be attributed not only to surgical, chemical and physical therapies improvement, but also to a more complete and accurated assistance to the neoplastic child . The constant support of an up-to-date and specialized laboratory and nursing staff may reduce the most common compliances of the neoplastic disease course and therapy . Neoplastic child with his family is facing a terrible stress, often with incumbent death risks . So a psychologic help is advisable for the whole family, and the best feeling is requested for the physicians . Supportive therapy must provide prevention and correction of the most common compliances of tumoral conditions, i.e . infections and hemorrhages . A correct and specific antibiotic therapy is absolutely necessary, but sometime is not sufficient . The introduction of hemoderivatives let us to spare the side effects of excessive whole blood transfusions, while the defective component may be selectively provided . Granulocyte transfusion recently introduced, may be the clue to the resolution of an overcoming infection.

Int J Clin Pharmacol Ther Toxicol, 1984 Jun, 22(6), 300 - 3
Pharmacokinetics of cefoxitin in patients with pleural effusion on a multiple dosage regimen; Garcia MJ et al.; The pharmacokinetics of cefoxitin were studied in 6 healthy volunteers and in 5 patients with pleural effusion of varied etiologies . The antibiotic was administered in a multiple dosage regimen of 30 mg/kg every 8 hours . Cefoxitin concentrations in serum and pleural fluid were determined after administration of the third dose corresponding to the levels of steady-state in both fluids . The elimination half-life of the antibiotic from the pleural fluid comes to 3.51 +/- 1.15 h, which is significantly greater than the serum half-life, (t 1/2 = 1.42 +/- 0.51 h) . This kind of multiple dosage regimen ensures therapeutic levels of cefoxitin in the pleural fluid during the entire treatment.

Br J Obstet Gynaecol, 1984 Jun, 91(6), 551 - 4
The transfer of cephradine across the placenta; Lange IR et al.; The transfer of maternally administered cephradine (1 g given intravenously) to the fetal circulation and amniotic fluid was investigated in 2 pregnant patients undergoing fetoscopy . Cephradine was detected in fetal serum between 23 and 72 minutes after injection and was present in therapeutic concentrations . Fetal serum levels appeared to peak at approximately 40-50 min . Amniotic fluid levels were rising during the sampling period of 97 min . Cephradine is transferred across the placenta and appears to be a suitable antibiotic for use in selected obstetric patients when penetration of the fetal compartment is desirable.

Arch Intern Med, 1984 Jun, 144(6), 1302 - 3
Tuberculous main-stem bronchial stenosis treated with sleeve resection; Caligiuri PA et al.; The unusual complication of bronchial stenosis from scarring due to tuberculosis developed in a 33-year-old woman, despite otherwise effective antibiotic therapy . She then was treated successfully with conservative surgical management by sleeve resection of the involved segment . This unusual sequela and its workup contain important implications for the management of tuberculosis.

South Med J, 1984 Jun, 77(6), 801 - 2
Pneumomediastinum after dental extraction; Ikard RW; In the preceding case, air dissection into the subcutaneous space and mediastinum was caused by the removal of an impacted third molar with a high-speed drill . Such surgery can result in a typical clinical complex lasting a few days and consisting of pain, dyspnea, fever, and leukocytosis . Because there is a potential for mediastinitis, antibiotic therapy is indicated.

Obstet Gynecol, 1984 Jun, 63(6), 859 - 62
Spontaneous occurrence of synergistic bacterial gangrene following external pelvic irradiation; Husseinzadeh N et al.; A case of spontaneous synergistic bacterial gangrene occurring after external pelvic irradiation is presented in a 25-year-old woman with invasive cervical cancer . Treatment consisted of aggressive antibiotic therapy and extensive excision and debridement followed by split-thickness skin grafting . Both recovery and cosmetic results were satisfactory . The pathophysiology, predisposing factors, and treatment modalities are presented.

Laryngoscope, 1984 Jun, 94(6), 802 - 6
Transtympanic iontophoresis: personal experience; Passali D et al.; After having described the method of application used for iontophoresis and the results of previous studies carried out by other authors in the hope of finding a definite use for its clinical application, the authors present their personal experience carried out with the use of various chemical substances applied to both the guinea pig and to man . The chemicals taken into consideration were those used in the treatment of otitis media: anti-inflammatory, antibiotic, and mucolytic products . Iontophoresis proved to be a simple and effective method for the treatment of certain middle ear diseases, and offered a more rapid recovery in comparison with subjects treated uniquely by traditional methods.

Lab Invest, 1984 Jun, 50(6), 673 - 82
Distribution of filipin-sterol complexes in villus goblet cell membranes of rat small intestine; Trier JS et al.; The polyene antibiotic, filipin, was used as a morphologic probe to determine the distribution of cholesterol in plasma and intracellular membranes in freeze fracture replicas of villus goblet cells from rat small intestine . Endoplasmic reticular and cis-face Golgi membranes displayed only rare filipin-sterol complexes . Membranes of the Golgi trans-face and adjacent nascent secretory granules revealed a moderate number of complexes . Membranes of mature secretory granules contained numerous filipin-sterol complexes, especially in sites where adjacent granules abutted . Complexes were so abundant on the apical plasma membrane that they approached confluence . The areal density of filipin-sterol complexes on the lateral plasma membrane was less than on the apical membrane but varied from goblet cell to goblet cell . The number of complexes on the lateral membrane of cells that appeared to be actively secreting mucus at the time of fixation was greater than on cells that showed no evidence of active mucus secretion . Thus, in villus goblet cells of rat small intestine (a) mucous granule membranes and the apical plasma membrane with which they fuse during secretion appear strikingly enriched with cholesterol, (b) cholesterol appears to be incorporated into mucous granule membranes during and shortly after their formation at the Golgi trans-face, and (c) the cholesterol content of the lateral plasma membrane of secreting goblet cells appears to be greater than that of nonsecreting cells.

Clin Orthop, 1984 Jun, (186), 71 - 4
Acetabular osteomyelitis in children; Gamble JG et al.; The clinical, laboratory, and roentgenographic features of acetabular osteomyelitis were present in a 20-month-old boy and a five-year-old girl . The clinical and laboratory parameters were similar in extracapsular acetabular osteomyelitis and septic arthritis of the hip . A secondary effusion was evident in roentgenograms in both conditions . Acetabular osteomyelitis responded to selected intravenous antibiotic therapy . Septic arthritis of the hip required immediate surgical drainage as well as appropriate antibiotic coverage.

Radiology, 1984 Jun, 151(3), 747 - 50
Inflammatory lesions of the groin: ultrasonic evaluation; Sandler MA et al.; Sonograms of 72 patients with pain and swelling in the groin due to intravenous drug abuse were reviewed, together with 2 cases which were due to trauma . There were 27 abscesses, 36 cases of cellulitis or thrombophlebitis, 7 cases of lymphadenopathy, 3 hematomas, and 1 pseudoaneurysm . Most abscesses presented as distinct masses, while cellulitis was seen most often as soft-tissue swelling . However, 5 abscesses were manifested sonographically as diffuse soft-tissue swelling without a distinct mass, while 8 cases of cellulitis appeared as a mass . In most cases, ultrasound was able to distinguish diseases requiring surgery or percutaneous drainage from those that should respond to medical therapy . In some cases, percutaneous aspiration and/or follow-up sonograms after antibiotic therapy will be necessary for a specific diagnosis.

J Biol Buccale, 1984 Jun, 12(2), 171 - 80
Distribution of filipin-cholesterol complexes in rat incisor odontoblasts; Goldberg M et al.; Using the polyene antibiotic filipin as a probe to visualize cholesterol on freeze-fracture replicas of membranes of young odontoblasts of rat incisor, we demonstrated that cholesterol-rich domains were present in cell processes, whereas only a small number of deformations induced by cholesterol-filipin interaction was observed in cell bodies . Except for a few large vesicles, intracellular membranes did not react with filipin . The large number of intramembrane particles observed on the plasma membrane of odontoblast processes did not affect the formation of visible filipin-cholesterol complexes.

J Neurosurg, 1984 Jun, 60(6), 1236 - 42
Bacterial aneurysms of the intracavernous carotid artery; Rout D et al.; Six cases of bacterial intracavernous carotid artery aneurysms of extravascular origin secondary to cavernous sinus thrombophlebitis are reported along with a review of 12 similar cases collected from the literature . Of the authors' six cases, there were three children and three adults . Meningitis was found in five patients . All patients received prolonged antibiotic therapy . Spontaneous resolution of the aneurysm occurred in one patient, thrombosis of the internal carotid artery in another, and progressive enlargement of the aneurysm was seen on sequential angiography in the other two . Evidence of associated arteritis was present in all of the patients . Carotid ligation for persistent ophthalmoplegia was carried out in two patients, of whom one had a giant aneurysm and the other progressive aneurysm enlargement . The results of treatment were good in all cases . The authors believe that carotid arteriography is obligatory in cases of cavernous sinus thrombophlebitis in which ophthalmoplegia persists despite adequate antibiotic therapy.

Jpn J Antibiot, 1984 Jun, 37(6), 991 - 1005
{Fundamental and clinical studies on latamoxef in the perinatal period}; Takase Z et al.; Fundamental and clinical studies on latamoxef (LMOX) in the perinatal period were carried out, and following results were obtained . Concentration of LMOX was showed high peak levels in maternal serum, umbilical serum and amniotic fluid . LMOX seemed to be a very transferable compound to human tissues . LMOX was administered to 28 cases of various perinatal infections . Clinical responses were excellent in 13 cases, good in 15 cases and poor in none . And 140 cases of prophylactic use in the field of perinatal period were evaluated in good . No side effect was seen and an abnormal laboratory finding, the increase of GPT, was observed in only 1 case . LMOX was a highly useful antibiotic in perinatal infections, the safe dose range of LMOX into the perinatal mothers was estimated to be 2 g/day, with the maximum safe dose being 4 g/day.

Antibiotiki, 1984 Jun, 29(6), 446 - 50
{Liver mono-oxygenases and the pharmacodynamics of carminomycin and rubomycin}; Bogush TA et al.; The effect of carminomycin on the activity of liver monohydroxygenases was estimated . It mas noted that in doses of 2, 3 and 4 mg/kg the antibiotic had no effect on the sleep duration in mice treated with hexenal . This meant that it did not change the activity of the enzymatic system . Induction and inhibition of liver monohydroxygenases did not influence the toxic effect of carminomycin used in doses of 5 and 10 mg/kg . It was also shown that the toxicity of both rubomycin and adriamycin decreased on induction and increased on inhibition of liver monohydroxygenases . Like adriamycin rubomycin lowered the activity of this enzymatic system . Administration of rubomycin in a dose of 5 mg/kg prolonged the duration of the hexenal sleep almost 1.5-2 times as compared to the control . The possible participation of liver monohydroxygenases in metabolic transformations of the antracycline antibiotics is discussed.

Trop Geogr Med, 1984 Jun, 36(2), 165 - 8
Melioidosis: certain interesting presentations and treatment; Wanvarie S; Eight cases of melioidosis with different clinical presentations are described . The compromised host defense is evident in view of the underlying conditions in all cases . Treatment with appropriate antibiotic combinations proved to be effective in curing the disease.

Burns Incl Therm Inj, 1984 Jun, 10(5), 309 - 12
Trial of a laminar air-flow enclosure for the control of infection in a burns operating theatre; Lilly HA et al.; A series of 22 patients with full-skin thickness burns had skin grafting operations in a Piekenrood-Vinitex BV open-topped laminar air-flow enclosure, and a parallel control series of 18 patients were grafted in the same operating room without the use of the laminar flow unit; the operating room in which both series of operations were performed had standard plenum ventilation with 20 air changes per hour . None of the patients acquired on their burns Staph . aureus of phage types and antibiotic sensitivity patterns corresponding with those isolated from carriers who were in the theatre at the time of the operation; 16 patients acquired on their burns strains of types corresponding with those of strains isolated from burns of other patients in the ward . Settle plates exposed during operations showed a relatively small reduction in bacterial counts associated with the use of the laminar flow enclosure.

J Oral Maxillofac Surg, 1984 Jun, 42(6), 349 - 55
Myospherulosis of the oral hard and soft tissues; Lynch DP et al.; Myospherulosis is a unique, inflammatory, granulomatous lesion, which results from the action of lipid substances on extravasated erythrocytes . Petrolatum-based antibiotic ointments are the most frequent etiologic agents of iatrogenically acquired lesions . Six intraoral cases of myospherulosis are presented, including the first reported case in oral soft tissues . The literature of reported cases is summarized and the epidemiology, histopathology, and ultrastructure of the lesions are discussed . Predisposing events and recommendations for future use of petrolatum-based antibiotic ointments are presented.

Antibiotiki, 1984 Jun, 29(6), 407 - 10
{Interaction of salts of transition metals with gramicidin S in chloroform}; Komarov EV et al.; Extraction of CuCl2, NiCl2, CoCl2 and MnCl2 from the aqueous phase to the organic gramicidin S containing phase (the phase ratio of 1:1) was studied with the method of molar ratios at constant concentrations of the salts and changing concentrations of the antibiotic . The composition of the forming intracomplex compounds was determined with the equilibrium shift method . It was shown that 2 ions of chlorine and 2 molecules of gramicidin S bound with 1 ion of the metals . The extraction constants were measured . The complex compounds of gramicidin S with copper chloride were the most stable.

J Maxillofac Surg, 1984 Jun, 12(3), 114 - 7
Pepleomycin-induced pneumonitis resulting in death; Watanabe I et al.; Two cases of fatal pneumonitis induced by pepleomycin, a new antitumour antibiotic analogous to bleomycin, are described . In the first case, the patient received radiation in combination with intra-arterial administration of pepleomycin to a total dose of 100 mg . for the treatment of an epidermoid carcinoma of the maxilla . The pulmonary changes were noted two weeks after cessation of the chemotherapy and the patient died of pulmonary insufficiency despite intensive therapy with antibiotics and a steroid . The other case with an epidermoid carcinoma of the cheek and oropharynx was treated by radiation and pepleomycin given to a total dose of 205 mg . Pepleomycin was replaced by predonin soon after bilateral shadows were noticed on a chest radiograph, but the patient died of pneumonitis 10 months later . Various factors which may affect the development of pulmonary toxicity by pepleomycin are discussed.

J Biomol Struct Dyn, 1984 Jun, 1(6), 1457 - 72
Structure and dynamics of netropsin-poly(dA-dT).poly(dA-dT) complex: 500 MHz 1H NMR studies; Gupta G et al.; Antibiotic netropsin is known to bind specifically to A and T regions in DNA; the mode of binding being non-intercalative . Obviously, H-bonding between the proton donors of netropsin and acceptors N3 of A and O2 of T comes as a strong possibility which might render this specificity . In netropsin there could be 8 proton donors: four terminal amino groups and four internal imino groups . However, methylation of the terminal amino groups does not alter the binding affinity of netropsin to DNA--but the modification of the internal imino groups significantly lowers the binding affinity . Hence, the logical conclusion is that netropsin may specifically interact with A and T through H-bonding and in order to do so, it should approach the helix from the minor groove . The present paper provides experimental data which verify the conclusion mentioned above . Using poly(dA-dT).poly(dA-dT) as a model system it was observed following a thorough theoretical stereochemical analysis that netropsin could bind to -(T-A-T) sequence of the polymer in the B-form through the minor groove by forming specific H-bonding . Models could be either right or left-handed B-DNA with a mono or dinucleotide repeat . By monitoring the 31P signals of free poly(dA-dT).poly(dA-dT) and netropsin-poly(dA-dT).poly(dA-dT) complex we show that the drug changes the DNA structure from essentially a mononucleotide repeat to that of very dominant dinucleotide repeat; however the base-pairing in the DNA-drug complex remain to be Watson-Crick . Whether H-bonding is the specific mode of interaction was judged by monitoring the imino protons of netropsin in the presence of poly(dA-dT).poly(dA-dT) . This experiment was conducted in 90% H2O + 10% D2O using the time-shared long pulse . It was found that exchangeable imino protons of netropsin appear in the drug-DNA complex and disappear upon increasing the D2O content; thus confirming that H-bonding is indeed the specific mode of interaction . From these and several NOE measurements, we propose a structure for poly(dA-dT).poly(dA-dT)-netropsin complex . In summary, experimental data indicate that netropsin binds to poly(dA-dT).poly(dA-dT) by forming specific hydrogen bonds and that the binding interaction causes the structure to adopt a Watson-Crick paired dinucleotide repeat motif.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemioterapia, 1984 Jun, 3(3), 159 - 62
Effect of gentamicin and sisomicin on the generation of superoxide by human monocytes; Dri P et al.; The effect of gentamicin and sisomicin on the generation of superoxide anions by human monocytes exposed to a phagocytosing stimulus, i.e . serum treated zymosan, or a soluble stimulus, i.e . 4-beta-phorbol-12-myristate-13-acetate, has been studied . Neither sisomicin nor gentamicin affected the superoxide production by stimulated monocytes . The data suggest that the reported variability in the response to aminoglycoside antibiotic therapy in certain clinical situations cannot be attributed to interference with monocyte oxidative burst.

J Biol Chem, 1984 May 25, 259(10), 6318 - 26
An inhibitor of mitochondrial respiration which binds to cytochrome b and displaces quinone from the iron-sulfur protein of the cytochrome bc1 complex; von Jagow G et al.; Myxothiazol, an antibiotic from Myxococcus fulvus, which inhibits mitochondrial respiration in the bc1 complex of the respiratory chain, has effects on the redox components of isolated succinate-cytochrome c reductase complex which suggest that it interacts with both cytochrome b and the iron-sulfur protein of the bc1 complex . The inhibitor appears to increase the midpoint potentials of cytochromes b-562 and b-566, as indicated by an increase in their reducibility by the succinate/fumarate couple . It also causes a red shift in the optical spectrum of ferrocytochrome b-566, as reported previously (Becker, W . F., Von Jagow , G., Anke , T., Steglisch , W . (1981) FEBS Lett . 132, 329-333) . This red shift is enhanced by Triton X-100, and there is no shift in the spectrum of b-562 . These results are consistent with evidence that mutations conferring myxothiazol resistance in yeast map to the mitochondrial gene for cytochrome b ( Thierbach , G., and Michaelis, G . (1982) Mol . Gen . Genet . 186, 501-506) . In addition, myxothiazol has effects on reduction of the cytochromes b and c1 by succinate or ubiquinol which are identical to those caused by removal of the iron-sulfur protein from the bc1 complex . It blocks reduction of cytochrome c1 during single and multiple turnovers of the bc1 complex, but does not block reduction of the b cytochromes . In the presence of antimycin, it blocks reduction of both cytochromes b and c1 . In contrast to antimycin, myxothiazol inhibits oxidant-induced reduction of both b cytochromes and does not inhibit their oxidation by fumarate . Myxothiazol also inhibits reduction of the iron-sulfur protein by ubiquinol and shifts the gx resonance in the EPR spectrum of the iron-sulfur protein from g = 1.79 to 1.76 . It does not affect the midpoint potential of the iron-sulfur protein, but does eliminate the increase in midpoint potential which is caused by inhibitory hydroxyquinones which bind to the iron-sulfur protein . The effects of myxothiazol are consistent with a protonmotive Q cycle pathway of electron transfer in which myxothiazol binds to cytochrome b and displaces quinone from the iron-sulfur protein of the bc1 complex . These results suggest either that a myxothiazol-induced conformational change in cytochrome b is transmitted to a quinone binding site on the iron-sulfur protein, or that there is a quinone binding site which consists of peptide domains from both cytochrome b and iron-sulfur protein.

J Biol Chem, 1984 May 10, 259(9), 5357 - 60
The product of the F sex factor traT surface exclusion gene is a lipoprotein; Perumal NB et al.; The product of the Escherichia coli sex factor F traT gene (TraTp), an outer membrane protein of Mr = 25,000, is covalently modified in vivo by the addition of glycerol and fatty acids . Consistent with this result, and as would be expected for a bacterial lipoprotein, the novel amino acid glycerylcysteine can be detected in purified TraTp . Being a secreted protein, TraTp is made from a signal sequence containing precursor, and glycerol and fatty acids can be detected in both the precursor and mature (processed) species of TraTp . The peptide antibiotic globomycin inhibits the cleavage of the pro-TraTp signal sequence, but not the glycerol and fatty acid modification . Diglyceride modification of the Cys residue at the site of signal sequence cleavage probably precedes and is a prerequisite for processing of the TraTp signal sequence . Thus, TraTp appears to be a typical E . coli lipoprotein, having a pathway for modification and processing that is similar to that of Braun's lipoprotein (the major outer membrane lipoprotein).

Am J Otolaryngol, 1984 May-Jun, 5(3), 177 - 82
Detection of aminoglycoside ototoxicity by high-frequency auditory evaluation: selected case studies; Fausti SA et al.; A practical monitoring procedure utilizing frequencies higher than those tested by conventional audiometry for the detection of ototoxicity has the potential for preventing or minimizing irreversible communication deficits in patients receiving aminoglycoside antibiotic therapy . If ototoxicity produced by these drugs could be detected before it progresses to involve the frequencies essential for communication, it might be possible to lower the dose or to change to another antibiotic to prevent a permanently handicapping hearing impairment . From a total of 77 patients monitored by serial audiograms, three case studies illustrate the various types of auditory sensitivity changes observed with high-frequency audiometry . Ototoxicity was generally detected by high-frequency auditory testing before it could be detected by conventional audiometric procedures . These cases demonstrate the utility of monitoring audition at frequencies higher than those tested conventionally in patients receiving aminoglycoside antibiotics.

Farmakol Toksikol, 1984 May-Jun, 47(3), 70 - 4
{Prenatal action of tetracycline hydrochloride on lymph node development in the rat}; Savitskaia TN; Histological and morphological methods were used to study the ante- and postnatal development of tracheobronchial and mesenterial nodes of white rats exposed to tetracycline in the preimplantation period (days 1-6 of the embryogenesis), during placentation and early organogenesis (days 8-13), and in the late organogenesis (days 14-19) . Administration of tetracycline on days 1-6 and 8-13 of the embryogenesis disturbs the formation of the morphofunctional structures of the node, inhibits the lympho- and plasmocytopoiesis associated with a dramatic increase in the number of granulocytes and mast cells . Exposure to the antibiotic on days 14-19 of the embryo-genesis does not impair the formation of the lymph nodes but leads to an increase in them of the number of lymphocytes, plasmocytes, macrophages, eosinophilic granulocytes and mast cells.

Farmakol Toksikol, 1984 May-Jun, 47(3), 66 - 70
{Effect of tetracycline hydrochloride on the development of the thymus structure in the rat}; Petrova TB; Histological, electron microscopy and morphological methods were used to study the structure of the thymus of Wistar rats in the antenatal and early postnatal ontogenesis after administering to their mothers of the therapeutic doses of tetracycline hydrochloride at varying times of pregnancy (days 1-6, 8-13, 14-19) . A study was also made of the alterations in the thymus of one-month-old rats exposed to the antibiotic prenatally in response to the administration of bacterial antigen.

Transfusion, 1984 May-Jun, 24(3), 240 - 1
Preparation of granulocyte concentrates for neonatal patient transfusion; Kalmin ND et al.; As an adjunct to antibiotic therapy, granulocytes for infusion often are required within hours of the diagnosis of neonatal sepsis . The logistics of obtaining granulocytes by leukapheresis were evaluated in order to provide, at short notice, a low volume, highly concentrated product . An average of 4.0 X 10(9) granulocytes in a mean volume of 101.5 ml of plasma was collected after processing an average of 3 liters of blood from each of three donors . Following centrifugation of these products, the volume of the final products was reduced by an average of 54.3 percent, while only 10.2 percent of the granulocytes were lost . One of the products, containing 4.8 X 10(9) granulocytes in a volume of 44 ml, was infused into a 3.4 kg septic neonatal patient within 4 hours of receipt of the order by the blood bank . We conclude that it is possible to collect high concentrations of granulocytes for neonatal transfusion in a timely manner by following the protocol described in this report.

Neurosurgery, 1984 May, 14(5), 567 - 9
Meningoencephalitis complicated by pituitary insufficiency and a spontaneously resolving suprasellar mass; Jew K et al.; A 53-year-old woman presented with acute meningoencephalitis associated with anterior and posterior pituitary insufficiency . A computed axial tomogram (CT) of the head revealed a suprasellar mass . The meningoencephalitis, presumably of bacterial origin, resolved after antibiotic therapy and, on a repeat CT, the suprasellar mass had disappeared . Five months after the initial illness, the patient's diabetes insipidus had resolved, anterior pituitary function had improved, and there was no sign of the suprasellar mass . The presence of a suprasellar mass in conjunction with acute meningoencephalitis and anterior and posterior pituitary insufficiency should raise the suspicion that the mass is not neoplastic and may be infectious or inflammatory in origin.

J Am Vet Med Assoc, 1984 May 1, 184(9), 1146 - 8
Esophageal anastomosis in two foals; Gideon L; Esophageal anastomosis was performed on 2 foals after resecting a midcervical stricture . Nasogastric tube alimentation and antibiotic therapy allowed these foals to recover, and they matured to useful performing horses . These cases demonstrated a feasible and successful surgical management regimen for the strictured esophagus.

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