J Am Vet Med Assoc, 1983 Nov 15, 183(10), 1076 - 80 Facial and vestibulocochlear nerve disease in six horses; Power HT et al.; In 6 horses, clinical signs of illness implicated a lesion involving the facial and vestibulocochlear nerves . One horse had signs of otitis externa . Five horses had radiographic changes primarily involving periosteal bony proliferation of the stylohyoid bone at its articulation with the temporal bone . Five horses improved with antibiotic therapy . Otitis media-interna was found at necropsy of one horse. J Mol Biol, 1983 Nov 5, 170(3), 795 - 6 Crystallization and preliminary X-ray diffraction results of trichorzianine A 1, a peptide with nineteen residues from Trichoderma harzianum; Bachet B et al.; Trichorzianine A 1 is one of the main components of a mixture of related antibiotic peptides (trichorzianines) produced by the fungus Trichoderma harzianum . Good crystals were obtained and allowed X-ray diffraction up to 0.8 A resolution . The space group is orthorhombic, C222(1), Z = 8, a = 64.8 (1) A, b = 9.33 (3) A, c = 39.9 (1) A . The solvent content is only 12%, preventing a heavy ion diffusion . So, we are trying to obtain the structure by direct methods. Jpn J Antibiot, 1983 Nov, 36(11), 3312 - 20 {Clinical study on drip infusion of micronomicin in the fields of surgery and gynecology}; Kikuchi K et al.; The drip infusion of micronomicin (MCR) in the field of surgery and gynecology was investigated . MCR was administered by drip infusion to 73 cases of surgical diseases and 31 cases of gynecological diseases . The clinical effective rate of MCR alone was 68% in all cases and that of MCR combined with other antibiotics was 89% . No remarkable side effect of drip infusion of MCR was found in all cases . Drip infusion of MCR was found to be as effective and safe as intramuscular injection of the antibiotic. J Antimicrob Chemother, 1983 Nov, 12(5), 497 - 502 Distribution to human peripheral lymph of amoxycillin and of ampicillin from the oral prodrug bacampicillin; Bergan T et al.; Equivalent doses of 1600 mumol each of amoxycillin (582 mg) and ampicillin from bacampicillin (800 mg) were studied in five fasting healthy volunteers in a cross-over study . Peripheral lymph was collected from the legs by cannulation of subcutaneous lymph vessels . Antibiotic concentrations were determined by bioassay . Passage to the lymph was rapid; for both agents lymph peaks occurred between 1-2 h after serum maxima . The compounds showed similar ranges of serum and of lymph concentrations; the mean individual peak concentration, area under the concentration curves, and elimination half-life in serum were 9.6 mg/l, 24.8 mg.h/l, and 0.80 h respectively for amoxycillin and 11.0 mg/l, 21.4 mg.h/l, and 0.93 h for ampicillin from bacampicillin . In lymph, the corresponding values were 5.5 mg/l, 21.9 mg.h/l, and 1.1 h for amoxycillin and 4.7 mg/l, 16.1 mg/l, and 1.0 h for ampicillin . The ratios between concentrations in lymph and serum were similar . The ratios between the total areas under the concentration curves was 0.88 +/- 0.19 for amoxycillin compared to 0.80 +/- 0.10 for ampicillin from bacampicillin . The areas under the lymph concentration vs . time curves ranged from 69-107% of the serum curve values of amoxycillin and 71-97% for ampicillin . Both drugs persisted longer in lymph than in serum . This pattern was somewhat more pronounced for amoxycillin, probably because of its more sustained serum concentrations due to delayed absorption . Thus the two antibiotics were similar in respect to passage into peripheral lymph. Arch Fr Pediatr, 1983 Nov, 40(9), 723 - 5 {Chronic polyarthritis in cystic fibrosis}; De Lumley L et al.; In a 8 year-old girl, presenting with cystic fibrosis and severe respiratory failure, a chronic polyarthritis with skin rashes occurred . Rheumatoid factor was lacking in the serum . Antibiotic treatments of the pulmonary infections resulted repeatedly in an improvement of both articular and cutaneous disorders . Thus, the trigger-action of the microbic infection was considered as the inducer of a "reactive arthritis". Antimicrob Agents Chemother, 1983 Nov, 24(5), 735 - 41 Effect of phosphate and amino acids on echinomycin biosynthesis by Streptomyces echinatus; Formica JV et al.; Streptomyces echinatus produces only echinomycin (quinomycin A), in contrast to other streptomycetes, which produce families of quinoxaline antibiotics differing in the amino acid composition of the oligopeptide (quinomycins A, B, B0, C, D, and E) or the structure of the sulfur-containing cross bridge (triostins A, B, and C) . Attempts were made to establish conditions for directed biosynthesis with S . echinatus . The lability of the peptide lactone to alkaline pH was obviated by using high levels of phosphate or HEPES {4-(2-hydroxyethyl)-1-piperazineethane-sulfonic acid} buffer in the production medium . Maintaining the pH below 7.5 resulted in an apparent stimulation of production . Amino acids which serve as structural components or as precursors of echinomycin were employed singly or in combination with nitrate in a chemically defined medium . Based on specific yield (micrograms of echinomycin per milligram of mycelia {dry weight}), D- and L-serine, D-alanine, L-valine, and L-phenylalanine produced equivalent yields of antibiotic which were approximately twofold greater than yields obtained with nitrate alone . In contrast, L-alanine, beta-alanine, and L-threonine produced a three- to fourfold stimulation of production . Although the other amino acids diminished antibiotic production, L-isoleucine, which ostensibly was inhibitory to production, supported the accumulation of a quinoxaline antibiotic in which the cross-bridge sulfur lacked a methyl group. Arch Intern Med, 1983 Nov, 143(11), 2081 - 4 Circulating immune complexes in prosthetic valve endocarditis; Hooper DC et al.; Using the Raji cell radioimmunoassay, we have determined circulating immune complex (CIC) levels in 36 patients with prosthetic valves during 38 episodes of fever . Fever resulted from prosthetic valve endocarditis (PVE) in 27 instances and from other causes in 11 instances . Peak initial CIC levels higher than 100 micrograms/mL occurred more frequently in the group with PVE, while peak initial CIC values less than 30 micrograms/mL were more frequent in the control group . Circulating immune complex levels fell substantially with completion of antibiotic therapy in 28 (78%) of the patients with PVE . Late CIC elevations were associated with drug-related rashes and replacement of persistently infected prostheses . Our data suggest that the predictive value of measurement of CIC levels in patients with fever and prosthetic valves is in excluding PVE in patients with CIC levels persisting below 30 micrograms/mL. Toxicol Appl Pharmacol, 1983 Nov, 71(2), 288 - 93 Enhancement of adriamycin toxicity by carboxymethylcellulose in mice; Decorti G et al.; Carboxymethylcellulose (CMC) (1% in 0.9% NaCl, 0.2 ml/10 g ip) a common suspending agent, enhanced adriamycin (ADR) (15 mg/kg ip) toxicity when administered to mice 5 hr before the antibiotic . Compared with ADR alone, this combination treatment produced, after 7 days, an increase in lethality from 15 to 80% . The pathologic analysis of hearts, livers, kidneys, and small bowels was performed, revealing an increase in the incidence and severity of hepatic damage in mice receiving ADR + CMC . Furthermore, reduced glutathione (GSH) was measured in livers of all mice; the animals treated with CMC and ADR + CMC showed a significant (p less than 0.01) reduction of hepatic GSH in comparison with controls and ADR-alone-treated animals . These data further confirm a crucial protective role for GSH in ADR toxicity and prove that CMC exerts an important biochemical effect on hepatic GSH. Mol Pharmacol, 1983 Nov, 24(3), 509 - 12 In vitro translational activity of messenger RNA following treatment of human colon carcinoma cells with sangivamycin; Glazer RI et al.; Total mRNA from human colon carcinoma cell line HT-29 treated with the pyrrolopyrimidine antibiotic, sangivamycin(7-deaza-7-carboxamidoadenosine), was assessed in vitro using a reticulocyte lysate translation system . Under conditions of known drug-induced cell lethality, sangivamycin-modified mRNA showed a diminished translational capacity . The decreased activity of drug-modified mRNA increased in proportion to the time-dependent cytocidal effects of sangivamycin in this cell line . These data suggest that the lethal effects of this drug may be associated, in part, with a reduced ability of drug-modified mRNA to sustain translation in situ. J Med Chem, 1983 Nov, 26(11), 1631 - 7 Tetracyclic chromophoric analogues of actinomycin D: synthesis, structure elucidation and interconvertibility from one form to another, antitumor activity, and structure-activity relationships; Sengupta SK et al.; Two different tetracyclic chromophoric analogues of actinomycin D have been synthesized by engaging two chromophoric DNA-binding functions in actinomycin D, i.e., 2-amino and 3-oxo, into either a 1,4-oxazin-2-one or an oxazole ring system . A third analogue has an extra quinone function at C-8 of the oxazole analogue . In all the analogues the chemical integrity of the peptide lactones of the parent antibiotic is kept intact, but their sterochemistry is altered . The analogues are designed as transport-modified prodrug forms of either the tricyclic active analogues of actinomycin D or actinomycin D itself . All analogues exhibit cytotoxicity that is several-fold less potent than AMD; they also have no binding affinity toward extracellular DNA . Nonetheless, the analogues of the first and the third series show improved antitumor activities (P388 leukemia, CDF1 mice) . In fact, two of these analogues having a phenyl substituent at the C-3 site of the oxazinone ring or the C-2 position of the 8-oxo-8H-oxazole ring exhibit the highest antitumor effects . Most of the analogues are active over a broader dose range than actinomycin D and are 6- to 16-fold less cytotoxic to human lymphoblastic leukemia (CCFR-CEM) cells in vitro . The analogues with the most pronounced antitumor activity are those that retain most elements in the peptide stereochemistry of actinomycin D and have a quinone function or demonstrate susceptibility of their chromophores to biotransformation. J Antibiot (Tokyo), 1983 Nov, 36(11), 1536 - 8 The use of doubly-labeled 13C-acetate in the study of streptolydigin biosynthesis; Pearce CJ et al.; Using {13C2}acetate the biosynthesis of streptolydigin has been investigated . It has been demonstrated that a total of 4 acetate units are incorporated into the antibiotic, 3 into the acyl side chain and 1 into the tetramic acid portion. Arch Mal Coeur Vaiss, 1983 Nov, 76(11), 1357 - 61 {Suppurating splenic infarction originating from endocarditis}; Trunet P et al.; Three cases of splenic infarction complicated by abscess formation during bacterial endocarditis are reported . In all three cases there were associated clinical abdominal signs and, in one case, there was persistently positive hemocultures . The diagnosis was made by CAT scanning . The three patients underwent splenectomy and one patient also underwent valve replacement the same day . The methods of early diagnosis of splenic complications during endocarditis and the indications of splenectomy are discussed . Ultrasonography and abdominal CAT scanning are the most sensitive diagnostic methods for splenic lesions . As splenic rupture is associated with a high mortality and this complication may occur at any time during infarction complicated by abscess formation, early splenectomy is justified when abdominal clinical signs are elicited associated with a persistent, infectious syndrome with or without positive blood cultures, under appropriate antibiotic therapy . Splenectomy should also be considered if valve replacement is carried out in the same circumstances to avoid infection of the prosthesis. J Cell Biol, 1983 Nov, 97(5 Pt 1), 1592 - 600 Rings of membrane sterols surround the openings of vesicles and fenestrae, in capillary endothelium; Simionescu N et al.; We investigated the distribution of sterols in the cell membrane of microvascular endothelium (mouse pancreas, diaphragm, brain, heart, lung, kidney, thyroid, adrenal, and liver) with the polyene antibiotic filipin, which reportedly has binding specificity for free 3-beta-hydroxysterols . In some experiments, concomitantly, cell-surface anionic sites were detected with cationized ferritin . Vessels were perfused in situ with PBS, followed by light fixation and filipin administration for 10 to 60 min . Tissues were further processed for thin-section and freeze-fracture electron microscopy . Short exposure (10 min) to filipin-glutaraldehyde solution resulted in the initial appearance, on many areas, of rings of characteristic filipin-sterol complexes within the rim surrounding stomata of most plasmalemmal vesicles, transendothelial channels, and fenestrae . Such rings were absent from the rims of the large openings of the sinusoid endothelium (liver, adrenal), coated pits and phagocytic vacuoles . After longer exposure (30-60 min), filipin-sterol complexes labeled randomly the rest of plasma membrane (except for coated pits, and partially the interstrand areas of junctions), and also marked most plasmalemmal vesicles . These peristomal rings of sterols were displayed mostly on the P face, and, at their full development, consisted of 6-8 units around a vesicle stoma, and 10-12 units around a fenestra . At their level, the intramembranous particles and the cell surface anionic sites were virtually excluded . Peristomal rings of sterols were also detected on the plasma membrane of pericytes and smooth muscle cells of the microvascular wall, which otherwise were poorly labeled with filipin-sterol complexes as compared to endothelial plasmalemma . It is presumed that the peristomal rings of cholesterol may represent important contributors to the local transient stabilization of plasma membrane and to the phase separation between cell membrane and vesicle membrane at a certain stage of their fusion/fission process. J Urol, 1983 Nov, 130(5), 971 - 2 Intrarenal abscess in a transplant organ; Rao MM et al.; We report the first case of an intrarenal abscess in a transplant organ . Diagnosis was made by ultrasonography and excretory urography, and was confirmed by percutaneous aspiration under ultrasonographic guidance . Surgical drainage and systemic antibiotic therapy resulted in complete resolution of the lesion and no change in renal function. J Infect, 1983 Nov, 7(3), 270 - 1 Successful treatment of meningitis with cefotaxime in an adult; Jones DK et al.; A case of severe bacterial meningitis complicated by alcoholism, lobar pneumonia and coma, is described . Although triple antibiotic therapy had been ineffective, the patient made a rapid and complete recovery when treated with cefotaxime alone. Antimicrob Agents Chemother, 1983 Nov, 24(5), 689 - 95 Genetic and enzymatic basis of hygromycin B resistance in Escherichia coli; Rao RN et al.; A plasmid conferring resistance to the aminocyclitol antibiotic hygromycin B was isolated from Escherichia coli . The gene conferring resistance to this drug was cloned in pBR322, and the gene was localized to a fragment of ca . 1,510 base pairs . Resistance to hygromycin B is determined by an aminocyclitol phosphotransferase that modifies hygromycin B and structurally related antibiotics . The specific modification of hygromycin B is a phosphorylation of the hydroxyl on the 4 position of the cyclitol ring (hyosamine) . The presence of the phosphotransferase in E . coli correlates with reduced accumulation of {14C}hygromycin B. Mol Cell Biol, 1983 Nov, 3(11), 2110 - 5 A stable bovine papillomavirus hybrid plasmid that expresses a dominant selective trait; Law MF et al.; We describe a bovine papillomavirus hybrid plasmid containing the neomycin resistance gene from Tn5 inserted into a mammalian cell transcriptional unit . This plasmid is maintained as a stable extrachromosomal element (20 to 100 copies per diploid genome) in mouse cells selected either for the transformed phenotype or for resistance to the aminoglycoside G418 . Cells selected for G418 resistance initially display a flat, nontransformed phenotype before exhibiting the gross morphological characteristics of transformation . The delay in the appearance of the transformed phenotype indicated that some intracellular event or series of events subsequent to the establishment of transcriptionally active bovine papillomavirus 1 hybrid plasmid is required for the manifestation of the transformed phenotype. J Pharmacol Exp Ther, 1983 Nov, 227(2), 308 - 15 Comparative effects of clindamycin and lincomycin on end-plate currents and quantal content at the neuromuscular junction; Fiekers JF et al.; The pre- and postjunctional effects of the lincosamide antibiotics, clindamycin and lincomycin, were studied in voltage-clamped transected twitch fibers of costocutaneous muscles of garter snakes (species Thamnophis) . Miniature end-plate currents and end-plate currents (EPCs) were recorded over a wide voltage range for each antibiotic . The amplitude and kinetics of these currents were studied and estimates of the quantal content of evoked transmitter release determined . High concentrations of clindamycin (2 X 10(-4) M) and lincomycin (2 X 10(-3) M) produced significant depression of EPC amplitude and a nonlinearity in the EPC-voltage relationships . The time constant of EPC decay was accelerated in clindamycin and the relationship between the time constant of EPC decay and membrane potential remained a single exponential function with a concentration-dependent loss of the voltage dependence . In contrast to clindamycin, lincomycin produced biphasic EPCs which consisted of two components, one faster and one slower than the control decay rate . The relative amplitude and decay rate of each component was both concentration and voltage dependent . Either increasing the concentration of lincomycin or membrane hyperpolarization decreased the amplitude ratio, iota slow/iota fast, and increased the ratio of the respective time constants, tau slow/tau fast . Clindamycin affected EPC decay amplitude and quantal content in the same concentration range, whereas lincomycin affected EPC decay at concentrations 20 times less than those required to reduce EPC amplitude and quantal content . These results suggest that the neuromuscular blocking effects of clindamycin involve both pre-and postjunctional sites, whereas the effects of lincomycin are primarily on the postjunctional receptor-channel complex. Biochimie, 1983 Nov-Dec, 65(11-12), 593 - 607 Gamma-radiolysis study of the reductive activation of neocarzinostatin by the carboxyl radical; Favaudon V; The activation of the antitumor protein antibiotic neocarzinostatin (NCS) by the carboxyl radical CO-2, a one-electron donor obtained selectively from gamma-ray irradiation of nitrous oxide-saturated formate buffer, has been investigated in the presence and in the absence of DNA at pH 4.7 and pH 7.0 . The reaction of NCS with CO-2 in the absence of DNA is followed by a marked red shift (420----441 nm) and a pronounced increase (X 8.8) of the fluorescence emission corresponding to the naphthalene moiety of the NCS chromophore . The light absorption spectrum shows in parallel a hypochromic change with considerable fine structure throughout the 250-400 nm wavelength range . When DNA is present, the fluorescence intensity at completion of the reaction is slightly reduced (by 5 to 15 per cent) and the maximum emission wavelength shifted to 436-438 nm . However, the bulk rate of reaction is not altered by DNA and is independent of the pH, of the temperature and of the concentration of NCS . The NCS concentration-independence of the reaction rate is consistent with a high intrinsic rate (k greater than 10(8)M-1 . s-1) for the reaction of CO-2 with the NCS chromophore . Complete reduction of the NCS chromophore involves a total of three electron-equivalents . The final product does not react with oxygen, shows no odd electron spin, and is unable to induce DNA strand scission . Its molecular state, however, is fundamentally different when gamma-ray irradiations are performed with DNA . This bears evidence of short-lived one electron or two-electrons reduced intermediates decaying via non-identical routes depending on the presence of the acceptor DNA . Actually, dose-related strand breaks appear in DNA exposed to the action of NCS and CO-2 . Some NCS chromophore-DNA covalent adducts are also found . DNA strand breakage by CO-2-activated NCS is correlated with thymine release and is inhibited by a redox-stable intercalating agent . The DNA-nicking process thus bears resemblance to that reported by other authors using mercaptans to initiate reductive activation of the NCS chromophore . However, some spectral differences are observed between the CO-2-reacted and the thiol-treated chromophores . Moreover, thymine release and strand scission in DNA incubated with CO-2 and NCS proceed under anaerobic conditions . It is proposed that the strict oxygen requirement for DNA damage by NCS in the presence of mercaptans is due, at least partly, to competition between oxygen and thiols for reaction with the same primary deoxyribose radical resulting from DNA attack by the reductively activated NCS chromophore. Ann Clin Lab Sci, 1983 Nov-Dec, 13(6), 453 - 73 Current status of leukocyte and platelet administration in cancer therapy; Walker EM Jr et al.; Leukapheresis and plateletpheresis are rather commonly performed in order to obtain single donor concentrates of granulocytes and platelets . These procedures, although relatively safe, present occasional risks to donors and recipients . Some of the occasional adverse problems experienced by donors include citrate toxicity or acute hypocalcemia, hypotension, hypervolemia, venospasm or vein occlusion, chills, anaphylactoid reactions, hemorrhage, abdominal pain or complications related to equipment failure and related technical problems . Potential risks to donors include those related to the receiving of six percent hydroxyethyl starch (HES), dextrans, or corticosteroids, lymphocyte depletion or immunosuppression, and effects on the complement system . Prophylactic granulocyte transfusions to prevent the occurrence of infections and associated complications in neutropenic patients have not proven to be efficacious; therapeutic granulocyte transfusions appear to be more effective . Indications for therapeutic granulocyte transfusions include those patients with known infections unresponsive to appropriately aggressive antibiotic chemotherapy over a two or three day period combined with findings of a peripheral granulocyte count less than 500 mm3 and especially those with counts below 100 mm3 and/or prolonged fever greater then 38 degrees C (100.4 degrees F) for 24 to 48 hours . In addition, the patient should have a reasonable chance for bone marrow recovery . Hazards or complications associated with granulocyte transfusions include: (a) immediate transfusion reactions, (b) hypersensitivity reactions, (c) pulmonary infiltrates, (d) alloimmunization, (e) transmission of infections, and (f) the possibility of Graft vs . Host (GVH) disease . The current best use of apheresis platelets is to provide therapeutic doses of single donor matched platelets for patients refractory to pooled random donor platelets . Alloimmunization represents the major complication of therapeutic platelet transfusion and is characterized clinically by the failure to achieve expected platelet count increments after transfusion . Future developments which might greatly improve the effectiveness of therapeutic and possibly prophylactic leukapheresis and plateletpheresis include the development of effective sedimenting agents with shorter biological half-lives, more efficient and less expensive methods of procurement of granulocytes and platelets, improved methods of cryopreservation of granulocytes and platelets, better methods for detecting and quantitating antigranulocyte and/or antiplatelet antibodies, and more efficient evaluation of possible synergism of granulocyte transfusions with antibiotic therapy and residual host defense . These improvements may be of great value in the effective utilization of granulocyte and platelet products and in determining which patients are most likely to receive the maximum benefit from granulocyte and platelet support. Gan To Kagaku Ryoho, 1983 Nov, 10(11), 2245 - 51 {Mechanism of action and resistance of antineoplastic agents}; Tanaka N; The mechanisms of action of, and resistance to, important anticancer agents are briefly described . Their selective toxicity is considerably high, and is chiefly due to the distribution and metabolism in the body . The selective toxicity of some DNA-binding drugs may be attributed to the structural difference of DNA, nucleosome and/or chromatin between neoplastic and normal cells . Some studies of reducing side effects are summarized . In our laboratory, we are studying drug-resistance and metastasis of tumor cells . Since the mechanism of natural resistance of gastric cancer, pulmonary cancer, and other refractory cancers may be related to acquired resistance of leukemia, studies on new agents against drug-resistant tumor cells are important . In our laboratory, we have selected cell sublines of murine T-lymphoblastoma L5178Y for resistance to adriamycin (ADM), aclarubicin (ACR) or bleomycin (BLM), and have observed that the resistance is attributed to decreased influx and increased efflux of the antibiotic, resulting in lowered retention of the drug in the cells . Each resistant subline shows a characteristic cross-resistant pattern, suggesting that membrane alteration involved differs each other . We have also found that glycoprotein-synthesizing activity and alkaline phosphodiesterase activity of plasma membrane are higher in the three resistant sublines than in the parental cell line . We obtained a number of hybridomas producing antibodies to plasma membrane of an ACR-resistant subline of L5178Y cells . Among the syngeneic monoclonal antibodies, one was found by agglutination tests to react with the ACR-resistant cell line, but not significantly with the parental and ADM-, BLM-and MCR-resistant cell lines . Fluorographs of {14C} leucine-labeled ACR-resistant cells demonstrates two protein bands of 230 K and 20 K daltons, which are precipitated by the monoclonal antibody . The former seems to be specific to the ACR-resistant cells . Based on the results so far obtained, the 230 K protein may be related to the drug resistance and may be TATA (tumor-associated transplantation antigen) . The results suggest that isolation of drug-resistant neoplastic cells is a novel method of finding TATA. Int J Pediatr Otorhinolaryngol, 1983 Nov, 6(2), 205 - 11 Subdural empyema of sinus origin in children; Heilbronn YD et al.; Two children with subdural empyema of paranasal sinus origin presented as neurological emergencies . Both had severe acute pansinusitis with complicating subdural empyema . The need for a high index of suspicion in the proper clinical setting is mandatory even in the absence of confirmatory contrast studies . Surgical proof should be immediately followed by adequate treatment . The high mortality rate even in the antibiotic area calls for this approach. J Biol Chem, 1983 Oct 25, 258(20), 12327 - 33 von Willebrand factor . A protein which binds at the cell surface interface between platelets; Senogles SE et al.; von Willebrand factor (VWF) functions in platelet aggregation, a form of cellular interaction . In vitro analysis of platelet aggregation, as measured by the platelet aggregometer, requires addition of a promoter such as the glycopeptide antibiotic ristocetin . Native multimeric VWF (Mr = 1-20 X 10(6)) can be reduced with sulfhydryl reagents to a monomeric state (Mr = 2 X 10(5)) . In this study, the binding of bovine VWF and ristocetin to bovine platelets was investigated using fluorescence anisotropy of derivatized monomer protein and ristocetin and also by radioisotope methods using 125I-labeled monomer and native protein . Ristocetin bound to bovine platelets but not to VWF . VWF binding to formaldehyde-fixed platelets was dependent on the presence of a promoter such as ristocetin . The monomer and multimer VWF bound equally well in the presence of low ristocetin concentrations . Under these conditions, plots of VWF binding versus platelet concentration were sigmoidal, indicating positive cooperativity with respect to platelets . At higher (100 micrograms/ml) ristocetin concentrations, the binding curve was no longer sigmoidal . Ristocetin promoted the formation of small platelet aggregates, an effect that was amplified by the presence of VWF . In fact, all conditions which resulted in monomer or multimer VWF binding to platelets also caused formation of platelet aggregates observed by light microscopy . These combined results were consistent with VWF binding only to the interface between proximal platelets . High affinity binding could be provided by the presence of two cell surfaces and the resulting multiple binding interactions . Polycations, such as poly(L-lysine) and Polybrene, also promoted the formation of platelet aggregates and facilitated the binding of VWF to platelets . Physiological platelet activators such as thrombin, ADP, and collagen also facilitated VWF binding to native platelets and caused platelet aggregation . It appears possible that any process which causes the surface membranes of platelets to become spatially close will allow expression of VWF activity. Thromb Res, 1983 Oct 15, 32(2), 215 - 22 Effect of intravenous carbenicillin, cefoxitin and cefamandole on ADP-induced platelet aggregation and shape change; Fedder IL et al.; The effect of a large daily dose of i.v . carbenicillin, cefoxitin and cefamandole on platelet aggregation with adenosine diphosphate (ADP) and the effect of carbenicillin on ADP induced shape change were evaluated . Six volunteers received carbenicillin 100 mg/kg every 4 hours . Three of them also received cefoxitin 3 gm every 6 hours and cefamandole 2 gm every 4 hours . All treatments were separated by 14 days . Prior to treatment, as well as 1 and 24 hours after the last dose of antibiotic, citrated platelet-rich plasma was tested for the extent of aggregation at a series of ADP concentrations . As previously reported by several groups, carbenicillin decreased the sensitivity of platelets in their aggregation response to ADP . Thus, the concentration of ADP needed to obtain 50% of maximal aggregation response was increased 3.5 +/- 1.7 (S.D.) fold . In addition, when measured separately, the sensitivity of platelets in their shape change response to ADP was decreased to a similar degree . The concentration of ADP needed to produce 50% of maximal shape change response was 2.8 +/- 1.6 (S.D.) fold higher after carbenicillin treatment . The results are in accordance with previous in vitro studies suggesting that carbenicillin interferes with the initial phase of platelet activation . Cefoxitin and cefamandole had no apparent effect on platelet aggregation. Arch Biochem Biophys, 1983 Oct 15, 226(2), 433 - 40 Cytoplasmic regulation of chloroplast translation in Euglena gracilis; Reardon EM et al.; A regulatory role for cytoplasmically derived proteins in chloroplast translation in organello was examined by analyzing protein synthesis in plastids isolated from cells of Euglena gracilis which had been treated with cycloheximide (CHI) . Incorporation of {35S}methionine by chloroplasts from CHI-inhibited Euglena was reduced approximately 40 and 90% by exposure of the cells to the antibiotic for 2 and 4 h, respectively . The chloroplast translation products were then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography . The synthesis of polypeptides in the soluble compartment of the plastid was substantially diminished by as little as 15 min of CHI pretreatment . No qualitative alterations of the polypeptide pattern were detected . Qualitative changes were seen in the thylakoid fraction, however . Comparison of the stainable polypeptides and fluorographs of thylakoid membranes from CHI-treated cells with those of controls showed several instances in which the more slowly migrating member of a doublet accumulated with a concomitant depletion of a more rapidly migrating component . A pair of polypeptides at 28 and 30 kDa, which we believe are the Euglena homologs of the photogene product and its precursor, respectively, are representative of this phenomenon . Additionally, thylakoids from cells pretreated with CHI sometimes synthesized novel polypeptides larger than 65 kDa . Finally, when intact chloroplasts from CHI-inhibited Euglena were incubated with a postchloroplast supernatant from normal cells, there was a partial reversion of the anomalies seen in the fluorographs . These data are interpreted to indicate the cytoplasmic origin of one or more proteins whose function is to process chloroplast translation products. Biochim Biophys Acta, 1983 Oct 13, 741(1), 123 - 7 G-418, an elongation inhibitor of 80 S ribosomes; Bar-Nun S et al.; The mode of action of the aminoglycoside G-418 was studied in wheat-germ, cell-free translation systems programmed with rat-liver polyadenylated RNA . Incorporation of amino acids into protein was effectively inhibited by G-418 in the microM concentration range . The inhibition pattern obtained was not uniform . The synthesis of polypeptides with higher molecular weights was more inhibited than that of smaller polypeptides . An identical inhibition pattern within a similar range of concentrations was obtained with cycloheximide, a known elongation inhibitor . Translation activity was abolished when the wheat-germ 80 S ribosomes were removed and could be partially reconstructed upon addition of the ribosomes . Incubation with G-418 prior to isolation yielded ribosomes defective in their reconstruction ability . The inhibition pattern was not uniform and exhibited again the same relationship between the size of a polypeptide and the extent of inhibition of its synthesis . Therefore, we suggest that in wheat-germ, cell-free translation systems G-418 affects the 80 S ribosomes and inhibits the elongation cycle. J Biol Chem, 1983 Oct 10, 258(19), 11851 - 5 Induction of amino acid transport system A in rat hepatocytes is blocked by tunicamycin; Barber EF et al.; Primary cultures of rat hepatocytes respond to hormones or amino acid deprivation by increasing System A-mediated neutral amino acid transport . Previous reports have shown this stimulation to be dependent on RNA and protein synthesis, whereas the present report describes the inhibition of System A by tunicamycin (TM), an inhibitor of asparagine-linked glycoprotein biosynthesis . The basal System A activity, as monitored by Na+-dependent 2-aminoisobutyric acid uptake, was decreased by TM when hepatocytes were cultured for 24 h in the presence of the antibiotic . System Gly activity was also sensitive to TM, whereas the activities of Systems L1, L2, and N were relatively resistant and that of System ASC was only moderately affected . The increase in System A-mediated uptake after incubation of hepatocytes in the absence of amino acids (i.e . adaptive control) was almost completely abolished by including TM . Likewise, stimulation of hepatic 2-aminoisobutyric acid transport by glucagon, dexamethasone, insulin, or vasopressin was also blocked by the inhibitor . When glucagon alone or glucagon plus dexamethasone was added, the inhibition by TM was transient such that the degree of inhibition decreased with incubation time after the initial 2 h . Addition of TM to cells which had been treated previously for 2 h to 4 h with glucagon and dexamethasone blocked any further increase in transport indicating that the glycoprotein component of System A must be continually synthesized to sustain the increase in activity . Treatment of hepatocytes with various lectins did not inhibit 2-aminoisobutyric acid transport. Sex Transm Dis, 1983 Oct-Dec, 10(4 Suppl), 263 - 70 Role of genital mycoplasmas in nongonococcal urethritis and prostatitis; Oriel JD; The roles of Mycoplasma hominis and Ureaplasma urealyticum in the pathogenesis of nongonococcal urethritis (NGU) remain controversial . Isolation and serologic studies and results of antibiotic therapy do not provide good evidence that M . hominis causes NGU . The results of some studies of therapy and of some experiments in which humans were inoculated with U . urealyticum indicate that this organism may cause some cases of NGU . However, U . urealyticum is ubiquitous and apparently nonpathogenic at other genital sites; thus there are serious difficulties in deciding its role in NGU . Chronic prostatitis is a poorly defined clinical entity . At present there is no convincing evidence that either M . hominis or U . urealyticum is involved in its pathogenesis. Hinyokika Kiyo, 1983 Oct, 29(10), 1329 - 37 {Eosinophilic cystitis: a report of 2 cases}; Hirano S et al.; Two patients with eosinophilic cystitis are presented in this report . The first case was a 39-year-old man who was admitted to our clinic with complaints of pollakisuria, pain on urination and hematuria for a month, which had not been relieved by antibiotic therapy . He had both a family and a personal past history of allergy . Excretory urograms showed a mild bilateral hydroureter and small bladder with irregular filling defects . Cystoscopic examination revealed velvety, ulcerated areas in the bladder mucosa, and we diagnosed these changes as eosinophilic cystitis after bladder biopsy . Steroid and antihistaminic therapy improved these symptoms . The second case was a 67-year-old woman who visited our clinic complaining chiefly of hematuria for 2 months . There was no predisposition to allergy, but she had a past history of uterine cancer which had been treated with irradiation . Cystoscopic examination disclosed a large amount of intravesical coagula, and erythematous and edematous areas with petechiae of the bladder mucosa . Bladder biopsy revealed hemangioma and eosinophilic cystitis . There was no recurrence of cystitis after the removal of the coagula without any other treatment. Sex Transm Dis, 1983 Oct-Dec, 10(4 Suppl), 331 - 4 Mycoplasma hominis infection of the central nervous system in newborn infants; Mardh PA; The incidence of infections of the central nervous system caused by Mycoplasma hominis in newborn infants is not known . However, such infections occur in both full-term and premature infants, either with or without malformations such as myelomeningocele . M . hominis has also been recovered from brain abscesses . Infected infants usually present with signs of meningitis or meningoencephalitis . Hydrocephalus may develop . The cerebrospinal fluid characteristically has a reduced glucose content and an elevated protein concentration . The white blood cell count is high, with a predominance of either mono- or polymorphonuclear leukocytes . Cerebrospinal fluid yields M . hominis but not other bacteria . Some newborn infants with M . hominis infection of the central nervous system die, whereas others survive and become healthy . In spite of adequate antibiotic therapy, some of those infected develop sequelae such as hemiplegia . Therapy with tetracycline or lincomycin can rapidly eradicate the organism from cerebrospinal fluid. Sex Transm Dis, 1983 Oct-Dec, 10(4 Suppl), 307 - 10 Mycoplasma hominis: a placental pathogen? Embree JE, Krause VW, Embil JA. Current information on the role played by Mycoplasma hominis in placental inflammation was reviewed . M . hominis is associated with chorioamnionitis and funisitis, but the clinical significance of this association in not clear . Further research on the role of the organism in perinatal disease is needed . Meanwhile, in a gravely ill infant with a history of prolonged rupture of the placental membranes, chorioamnionitis, and funisitis, M . hominis should probably be considered a potential pathogen, cultures for this organism should be performed, and therapy with an antibiotic regimen effective against M . hominis should be instituted. Antimicrob Agents Chemother, 1983 Oct, 24(4), 533 - 7 Effect of piperacillin on tobramycin pharmacokinetics in patients with normal renal function; Lau A et al.; Aminoglycosides are inactivated by extended-spectrum penicillins in vitro and in patients with end-stage renal failure . In this prospective controlled study, we determined the effect of piperacillin on tobramycin pharmacokinetics . In 10 clinically stable male patients with calculated creatinine clearances of greater than or equal to 60 ml/min, serial levels in serum of tobramycin alone and after single 4-g intravenous doses of piperacillin were determined . No statistically significant changes in the concentration of drug in serum, the half-life (t1/2), the elimination rate constant (Ke), the volume of distribution (Vd), or the area under the serum concentration-time curve (AUC0-oo) occurred when tobramycin was used concurrently with piperacillin . Therefore, this antibiotic combination will not result in a clinically significant interaction in patients with normal renal function. Antibiotiki, 1983 Oct, 28(10), 760 - 3 {Alteration of the acute toxicity and various pharmacologic effects of streptomycin sulfate by calcium 4'-phosphopantothenate}; Dorofeev BF et al.; The effect of calcium 4'-phosphopantothenate (CPP) on acute toxicity of streptomycin and the decrease by the antibiotic of the muscle working capacity, "holes" reflex, body temperature and oxygen intake was studied on 258 albino mice weighing 22-26 g . Medical calcium pantothenate (CPA) was used for control purposes . CPP is an antagonist of streptomycin sulfate . In a dose of 1/10 or 1/5 of the LD50 injected intraperitoneally CPP lowered acute toxicity of streptomycin and prevented its effect in a dose of 0.11--1.1 g/kg injected subcutaneously on the muscle working capacity, "holes" reflex and body temperature . The spectrum index of the CPP antitoxic effect was equal to 22.5 . By its acute toxicity CPP (LD50 1.18 +/- 0.07 g/kg) did not differ from CPA (LD50 1.25 +/- 0.08 g/kg) . The efficacy of CPP, by its antitoxic spectrum, was 1.8 times higher than that of CPA . CPA lowered the streptomycin effect on the "holes" reflex and body temperature, while CPP prevented it . Both the drugs did not influence the decrease in the oxygen consumption induced by streptomycin. Antibiotiki, 1983 Oct, 28(10), 751 - 4 {Bioavailability of levomycetin preparations for oral use}; Batuashvili TA et al.; Bioavailability of chloramphenicol pharmaceutical forms prepared with the use of antibiotic substances differing in their dispersion levels was studied . It was shown that the level and rate of the drug absorption into blood did not always depend on the size of the substance particles . Fine crystalline substances of the antibiotic manufactured by two firms almost not differing in their dispersion levels markedly differed in the rate of antibiotic transfer into solution and the level of its blood absorption in humans . Tablets prepared with the use of the above substances were also characterized by various bioavailability levels . Study of the dissolution rate of separate fractions of the same substance revealed dependence of this parameter on the particle size. Am J Anat, 1983 Oct, 168(2), 213 - 28 The Sertoli cell junctional complex: structure and permeability to filipin in the neonatal and adult guinea pig; Pelletier RM et al.; The development and maintenance of the Sertoli cell junctional complex were investigated in prepubertal and adult guinea pigs . To correlate the structure of the blood-testis barrier with its permeability, the polyene antibiotic filipin (a cholesterol-binding agent of low molecular weight: 570.70) was added to the fixative as a tracer visible in freeze-fracture replicas . Discontinuous zonules, intermediate junctions (i.e., adhering fasciae) and gap junctions all proved permeable to filipin in the two age groups . Only the continuous occluding zonules characteristic of the adult guinea pig's testis were impermeable to the tracer . In pubertal animals, the establishment of the blood-testis barrier coincided with the completion of the junctional strands in occluding zonules . The formation of occluding zonules was similar in the newborn and the adult . In the adult, the Sertoli cell junctional complexes contained three types of cell junctions: occluding, adhering, and gap junctions . The sequence of occluding and adhering junctions from the base to the apex of the epithelium was the reverse of that demonstrated in most epithelia . The impermeable continuous occluding zonules at the base showed parallel patterns of uninterrupted junctional strands, whereas the permeable discontinuous zonules found higher in the epithelium showed a meandering pattern of broken strands . Our observations indicate that (1) Sertoli cell junctional complexes form near the young germinal cells at the base of the seminiferous epithelium and break down near the older germinal cells toward the apex; (2) the various patterns and orientations of the junctional strands reflect, respectively, the different stages of disintegration of the occluding zonules and the conformation of the mature Sertoli cell to the irregular contours of the germinal cells; (3) there is no relationship between permeability and junctional strand orientation; and (4) the cellular contacts between Sertoli cells and germinal cells situated below the blood-testis barrier may represent the early stages of formation of junctional elements which ultimately become incorporated into the Sertoli cell junctional complex. Br J Exp Pathol, 1983 Oct, 64(5), 559 - 69 The role of naturally-acquired bacterial infection in influenza-related death in neonatal ferrets; Husseini RH et al.; Concomitant, naturally-acquired bacterial infection was the cause of some deaths occurring in neonatal ferrets infected with the attenuated influenza virus A/Puerto Rico/8/34, these being prevented by antibiotic therapy . Bacterial infection played an insignificant role in the greater number of deaths following inoculation with the virulent clone 7a (of the recombinant influenza virus A/Puerto Rico/8/34-A/England/939/69/(H3N2} . As seen previously with clone 7a some ferret neonates infected with A/PR/8/34 died either from obstruction in the upper respiratory tract or from viral pneumonia, but with the latter virus, both types of lesion were probably attributable to the bacterial superinfection. Nurse Pract, 1983 Oct, 8(9), 13 - 19, 23 Pelvic inflammatory disease: a review of therapy; Loucks A; Pelvic inflammatory disease (PID) is a serious health problem that affects the reproductive capacity and the sexual activities of women . Approximately 50,000 cases are reported annually resulting in severe pain, reduced fertility and costly health care . Diagnosis of PID requires a complex analysis of the history, a thorough physical examination and diagnostic testing . Goals of care include accurate diagnosis with particular emphasis on differential diagnosis, antibiotic therapy, close follow-up and counseling . Antibiotic therapy is directed against the pathogenic organism, either gonococcal or nongonococcal . Careful counseling and follow-up aids successful treatment and decreases the likelihood of infertility. Gastroenterol Clin Biol, 1983 Oct, 7(10), 812 - 7 {Celiac disease, dermatitis herpetiformis and erosive jejunoileitis}; Eugene C et al.; A 21-year-old man with coeliac disease and dermatitis herpetiformis presented successively with erosive ileitis (warranting surgical resection) and erosive jejunitis (proven by jejunoscopy) . Discontinuous antibiotic therapy was associated with a gluten-free diet and evolution was favorable as judged with five years follow-up . Malabsorption with mucosal ulcerations can be due to: a) chronic ulcerative duodeno-jejuno-ileitis or Jeffries' disease; b) coeliac disease which may be classified as possible, probable, or certain according to the strictness of criteria . Our case is the fourth in which a villous response was proven after gluten-free diet . It is also particular in that the erosions were superficial; c) malignant lymphoma which can reasonably be excluded here . This observation confirms that a gluten-free diet may be effective after surgical resection of the ulcerated segment in complicated coeliac disease and shows that antibiotics may be an useful adjuvant to therapy. Biophys J, 1983 Oct, 44(1), 39 - 47 Pressure effects on alamethicin conductance in bilayer membranes; Bruner LJ et al.; We report here the first observations of the effects of elevated hydrostatic pressure on the kinetics of bilayer membrane conductance induced by the pore-forming antibiotic, alamethicin . Bacterial phosphatidylethanolamine-squalene bilayer membranes were formed by the apposition of lipid monolayers in a vessel capable of sustaining hydrostatic pressures in the range, 0.1-100 MPa (1-1,000 atm) . Principal observations were (a) the lifetimes of discrete conductance states were lengthened with increasing pressure, (b) both the onset and decay of alamethicin conductance accompanying application and removal of supra-threshold voltage pulses were slowed with increasing pressure, (c) the onset of alamethicin conductance at elevated pressure became distinctly sigmoidal, suggesting an electrically silent intermediate state of channel assembly, (d) the magnitudes of the discrete conductance levels observed did not change with pressure, and, (e) the voltage threshold for the onset of alamethicin conductance was not altered by pressure . Apparent activation volumes for both the formation and decay of conducting states were positive and of comparable magnitude, namely, approximately 100 A3/event . Observation d indicates that channel geometry and the kinetics of ion transport through open channels were not affected by pressure in the range employed . The remaining observations indicate that, while the relative positions of free-energy minima characterizing individual conducting states at a given voltage were not modified by pressure, the heights of intervening potential maxima were increased by its application. Ann Thorac Surg, 1983 Oct, 36(4), 464 - 7 Neonatal lung abscess: resection using one-lung anesthesia; Weber TR et al.; Three neonates with lung abscess unresponsive to antibiotic therapy underwent successful resection of infected lobes with the aid of one-lung anesthesia . This was accomplished by selective endobronchial intubation of the opposite lung and obstruction of the ipsilateral main bronchus with a Fogarty balloon-tipped catheter . This valuable technique provides protection against tracheobronchial spillage of purulent material and results in the rapid recovery of these seriously ill neonates. Ann Thorac Surg, 1983 Oct, 36(4), 408 - 10 The human tumor clonogenic assay in the treatment of patients with lung cancer; Kitten CM et al.; The human tumor clonogenic assay has allowed the growth of human tumor cells and their testing to chemotherapeutic agents in vitro in a manner much like bacterial antibiotic sensitivities . This report deals with the in vitro test results compared with the in vivo therapeutic sensitivities of human lung cancer . Three hundred twenty-six lung tumor specimens from either primary or metastatic disease were plated using a two-layer technique . Of these, 68% (223) were grown and 41% (133) were applicable to chemosensitivity testing . Only 28 patients were considered for a retrospective analysis of in vitro tumor sensitivity versus in vivo tumor response to chemotherapeutic agents . Among them the percentage of true positives for the assay was 60%, while the percentage of true negatives was 91% . This technique has been encouraging in its initial stages and, with further development, may have an expanding role in the treatment of patients with lung cancer. Ann Surg, 1983 Oct, 198(4), 420 - 9 Coverage of the infected wound; Mathes SJ et al.; Fifty-four consecutive patients with chronic wounds were identified by the following criteria: (1) established infection for 6 months, (2) exposure of bone, mediastinum, or other vital structure, (3) mechanical and/or vascular limitations to delayed closure techniques, (4) no response to wound debridement in prolonged antibiotic therapy . These wounds were divided into four groups: osteomyelitis (21), pressure sore (17), soft tissue wound (10), and osteoradionecrosis (6) . Wound treatment in all patients included debridement, muscle flap closure, and culture specific antibiotic therapy . These consecutively treated patients over a 4-year period presented with an average duration of chronic infection of 2.9 years . Ninety-three per cent of these patients after treatment have demonstrated stable coverage without recurrent infection with a minimum of 1 year and a maximum of 4.6 years follow-up . The results demonstrate safe, effective coverage (93% of patients) of chronic infected wounds associated with long bone and pelvic osteomyelitis as well as chronic perineal sinuses following proctocolectomy and osteoradionecrosis . Debridement with short-term (average 12 days) antibiotic therapy has been effective when muscle flap coverage is provided. Am J Gastroenterol, 1983 Oct, 78(10), 632 - 3 Pseudomembranous colitis: a possible role for Gallium scanning; Kramer EL et al.; A case of antibiotic-associated pseudomembranous colitis is presented in which the Gallium scan was the first diagnostic modality to alert the clinicians to the existence of an inflammatory bowel process . The mechanism of localization of the radiopharmaceutical in inflammatory bowel disease is discussed . Although colonoscopy is far more specific and should be the first-line diagnostic tool used in assessing the presence of pseudomembranous colitis, Gallium scanning may have a role in the follow-up of treatment and in cases of relapse. South Med J, 1983 Oct, 76(10), 1299 - 302 Profound neutropenia associated with benzylpenicillin; Snavely SR et al.; A 31-year-old white man with suspected aspiration pneumonia complicated by multiple pulmonary abscesses had profound neutropenia during a course of high-dose benzylpenicillin therapy for suspected bacterial endocarditis . Antigranulocyte antibodies were identified in the patient's serum . Leukopenia is an uncommon but potentially serious complication of therapy with this drug . We recommend weekly monitoring of blood counts during prolonged therapy with any beta-lactam antibiotic. Postgrad Med, 1983 Oct, 74(4), 156 - 7, 160 It is really sinusitis? Kern EB. To answer the question Is it really sinusitis? one must take a careful history, look into the nose, palpate the infected sinuses, and obtain roentgenograms . A history of pain, mucopurulent discharge, nasal obstruction, and systemic involvement should be present for a diagnosis of acute suppurative sinusitis . Physical findings and the presence of a predisposing factor help in the diagnosis, and roentgenographically demonstrated changes of the involved sinus can substantiate it . Acute suppurative sinusitis necessitates antibiotic therapy, which should be continued for seven days after the primary symptoms are relieved in order to avoid recurrence or development of subacute or chronic suppurative sinusitis . Chronic sinusitis requires surgical intervention to remove the diseased mucosa, and the sinuses must be ventilated (oxygenated) for resolution to occur. Antimicrob Agents Chemother, 1983 Oct, 24(4), 544 - 51 Susceptible Escherichia coli cells can actively excrete tetracyclines; McMurry LM et al.; Escherichia coli shows severalfold less susceptibility to tetracyclines when grown in enriched medium than in minimal medium . Transport studies with cells harvested from these media showed different handling of the drugs . Whereas an energy-dependent uptake of tetracycline and minocycline was observed in susceptible K-12 and wild-type E . coli strains grown in minimal medium, an active efflux of minocycline and, to a lesser extent, tetracycline was seen in cells grown in L broth and other enriched media . This efflux was replaced by an active uptake system after treatment of cells grown in L broth with EDTA . When assayed at a lower temperature (27 degrees C), even cells grown in minimal medium showed an efflux of minocycline . Everted membrane vesicles prepared from susceptible cells grown in minimal medium or L broth showed an energy-dependent accumulation of minocycline and tetracycline when supplied with certain divalent cations . These results suggest that an active efflux of tetracyclines occurs in susceptible E . coli but is not detected in cells grown in minimal medium because greater permeability of the outer membrane allows a more rapid active uptake . This efflux system is distinct from that specified by tetracycline resistance determinants . Since the active efflux of minocycline in cells grown in L broth disappeared at external antibiotic concentrations of greater than 100 microM, it may be saturable and so mediated by a membrane carrier. J Natl Cancer Inst, 1983 Oct, 71(4), 841 - 7 Cytotoxicity and sister chromatid exchanges induced in vitro by six anticancer drugs developed in the People's Republic of China; Huang CC et al.; Growth inhibition in the Chinese hamster cell line V79 and in the human lymphoid cell line Raji and induction of sister chromatid exchange(s) (SCE) in V79 cells after treatment with six anticancer drugs {harringtonine (HRT), homoharringtonine (HHRT), camptothecin (CPT), hydroxycamptothecin (HCPT), lycobetaine (LBT), and oxalysine (OXL)} developed in the People's Republic of China were studied . OXL is a new antibiotic; all other drugs are plant extracts . All drugs caused a dose-dependent growth inhibition in both cell types, as evidenced by decreases in plating efficiencies of V79 cells and in viable cell counts of Raji . However, the degree of inhibition differed widely among the drugs . HRT, HHRT, CPT, and HCPT were the most potent growth inhibitors, LBT was next, and OXL was the least effective inhibitor . SCE analyses were made in V79 cells treated with a drug in the presence or absence of the metabolic activation system S9 mixture (S9 mix), except for the HRT assay in which the S9 mix was not used . CPT, HCPT, and LBT induced a dose-dependent increase in SCE frequencies, while HRT, HHRT, and OXL caused no SCE induction at any dose level used . CPT was the most powerful SCE inducer . HCPT induced SCE but at a much reduced rate when compared to that of CPT . LBT was a weak SCE inducer; SCE induction was seen only in cultures treated with 40 micrograms or more LBT/ml . Addition of the S9 mix did not alter SCE frequencies, indicating that the drugs were direct-acting agents . HRT and HHRT were highly toxic, but they induced no increases in SCE frequency, indicating that cytotoxicity of a compound does not necessarily correlate with SCE induction. Am Surg, 1983 Oct, 49(10), 554 - 7 Colorectal perforation in renal transplant recipients; Nghiem DD et al.; Of 525 patients who received 585 renal transplants, seven developed colonic perforations from 6 to 27 days post-transplantation . Six were undergoing antirejection therapy at the time of perforation . Prompt diagnosis was made and colonic resection carried out immediately under broad spectrum antibiotic coverage . Primary gastrointestinal reconstruction was performed in one instance and colonic exclusion in the others . One patient died from the insult; three are alive eight to 42 months after perforation; and three succumbed to late unrelated problems at two, three, and 24 months . Early diagnosis, immediate thorough debridement of the peritoneal cavity, and colonic exclusion carry the best prognosis. Anal Biochem, 1983 Oct 1, 134(1), 73 - 81 Single-cell partition analysis--a direct fluorescence technique for examining ligand-macromolecule interactions; Graves DE et al.; Single-cell partition analysis is described as a novel technique for examining ligand-macromolecule interactions . This procedure is a combination of the classical fluorescence titration technique and phase-partition techniques and allows three separate methods for calculating and comparing both free and bound drug concentrations . The value of this technique is demonstrated by the comparison of the binding properties of the potent antitumor antibiotic adriamycin and ethidium bromide to nucleic acids . Binding isotherms of both drugs were obtained at low r (concentration of bound drug per base pair) values, showing strikingly different results, thus allowing insight to be gained into the cooperative binding of these drugs to DNA. Ann Ophthalmol, 1983 Oct, 15(10), 968 - 74, 977-79 Management of infectious endophthalmitis by combined vitrectomy and intraocular injection; Chen CJ; Combined therapeutic vitrectomy and intraocular antibiotic injection were used as a primary treatment for infectious endophthalmitis after diagnostic vitreous tap on seven patients . Two patients also received penetrating keratoplasty in addition to vitrectomy . Postoperatively, two patients achieved visual acuity of 20/30 or better, and five patients achieved 20/100 or better . One eye was enucleated. Antimicrob Agents Chemother, 1983 Oct, 24(4), 552 - 9 Novel synergism of two antifungal agents, copiamycin and imidazole; Uno J et al.; Copiamycin, a macrocyclic lactone antifungal antibiotic, was found to potentiate the antifungal effect of imidazole compounds, ketoconazole in particular . The potentiation of two nominally fungistatic agents in vitro was substantiated by a marked reduction of the minimum inhibitory and minimum fungicidal concentrations when the drugs were used in combination . The effectiveness of this synergistic combination was also demonstrated in experimental murine candidosis . Evidence is presented to suggest that this combined effect is due, at least in part, to the ionophoretic property of copiamycin . Whereas amphotericin B induces a marked increase in cellular permeability, this antibiotic does not possess the ionophoretic action of copiamycin, indicating that the enhancement of copiamycin activity and significant reduction of amphotericin B activity by ketoconazole pretreatment can be ascribed not only to changes in membrane permeability of the test organisms, but also to the different action mechanisms of copiamycin and amphotericin B . It is thus plausible that the strong synergism of copiamycin with imidazole compounds is related to the ionophoretic activity of the antibiotic . Further studies on the biochemical mechanism of this synergistic effect are being conducted together with an assessment of the clinical significance of this drug combination. Z Gastroenterol, 1983 Oct, 21(10), 601 - 3 Penetration of cefotaxime into the pancreas; Lankisch PG et al.; After intravenous injection of cefotaxime, higher pancreatic concentrations of the antibiotic were found in rats with experimental pancreatitis than in control animals . Also in human pancreatic pseudocysts, high and persistent concentrations of cefotaxime were found following intravenous injection . The results justify the use of cefotaxime in acute pancreatitis, whenever an antibiotic is indicated. J Antimicrob Chemother, 1983 Oct, 12 Suppl C, 39 - 50 Alkalinization of the intralysosomal pH by clindamycin and its effects on neutrophil function; Klempner MS et al.; Clindamycin is concentrated within human neutrophils and their lysosomes because the intralysosomal pH is highly acidic and this antibiotic behaves as a weak base . We have examined the ability of clindamycin to buffer (alkalinize) the intralysosomal pH and studied the consequences of alterations of lysosomal pH on neutrophil functions . At therapeutic concentrations of clindamycin (0.01 mM), we observed no effect on intralysosomal pH as monitored by the distribution and fluorescence of a weakly basic fluorescent probe 9-aminoacridine . However, at higher concentrations (1.0 mM), clindamycin alkalinized the intralysosomal pH and inhibited neutrophil lysosomal degranulation to several stimuli, and superoxide production in response to phorbol myristate acetate . Neutrophil locomotion was unaffected even at concentrations of clindamycin which increased the intralysosomal pH . We conclude that clindamycin accumulates in acidic neutrophil lysosomes and, at high concentrations, alkalinizes the intralysosomal pH . Coincident with lysosomal alkalinization there is inhibition of secretion and respiratory burst activity suggesting that intact lysosomal pH regulation is important for these functions . Clindamycin provides a useful tool to examine the relationships between weak base uptake, lysosomal pH and neutrophil functions. Anal Biochem, 1983 Oct 1, 134(1), 11 - 5 An enzymatic method for inosine 5'-monophosphate in the femtomole range; Young DA et al.; A method for measuring inosine 5'-monophosphate (IMP) by enzymatic generation of NADPH is described . Procedures are given for direct fluorometric assay in the nanomole range and indirect measurement with amplification by enzymatic cycling in the pico- and femtomole ranges . The most sensitive procedure represents a nearly 50,000-fold increase in sensitivity over enzymatic methods now available . Specificity of the assay was greatly enhanced by the use of the antibiotic coformycin, a potent inhibitor of adenosine deaminase (EC 3.5.4.4) . This enzyme was found to be a major contaminant of one of the necessary enzymes, phosphoglucomutase (EC 2.7.5.1) . The use of the method is illustrated by measurements of IMP in single stimulated and control rat muscle fibers. Aktuelle Traumatol, 1983 Oct, 13(5), 205 - 9 {Clinical experiences with a fibrin-nebacetin-spongy bone seal in the treatment of chronic bone infections and as local prophylaxis of infection in uninfected bones}; Goudarzi YM; Clinical experiences with Fibrin-Nebacetin-bone marrow combination for the treatment of chronic bone infection and as local prophylaxis by operation of non-infected bone diseases . Since 1979 we have carried out 33 autologous bone graftings in children and used the Fibrin-Nebacetin-bone marrow combination . Nebacetin provides a most effective local antibiotic therapy as supplementary and consecutive treatment are surgical procedures executed in bone infection . The chronic bone infection of 15 children subsided completely . In 18 children with bone transplants no infections was observed and all the patients showed primary healing . The use of fibrin did not disturb the bone reconstruction . After 12 weeks the reconstruction of the bone was almost complete . In two cases only we had to make a reoperation, caused by a recurrent cyst . We could not observe any hepatitis in our patients . The operative technique and advantages of treatment were discussed. Toxicol Appl Pharmacol, 1983 Oct, 71(1), 93 - 100 Trifluorinated ether anesthetic lethality in rats: the role of bacterial infection; Dersham G et al.; The lethal effects of the fluorinated ether anesthetics fluroxene (2,2,2-trifluoroethyl vinyl ether) and its ethyl (TFEE) and allyl analogues in male Wistar rats have previously been demonstrated to be potentiated by specific hepatic microsomal cytochromes P-450, and mediated by the common metabolite 2,2,2-trifluoroethanol (TFE) . We report here that administration of lethal combinations of anesthetic and cytochrome P-450-inducing agents or of lethal doses of TFE (0.21 g/kg and higher) to rats caused decreased white blood cell counts, necrosis of sternum bone marrow cells and lymphocytes in the thymic cortex, and resulted in Escherichia coli contamination of the blood, lungs, liver, and kidneys of treated rats . Control animals in identical environments were free of bacterial contamination . Pretreatment of rats with the antibiotic tetracycline-HCl in the drinking water (0.6 g/liter) from 24 hr before anesthetic or TFE administration significantly diminished the mortality . With TFEE and beta-naphthoflavone induction, mortality was reduced from 85 to 30% by the antibiotic . However, the antibody plaque assay following immunization with sheep erythrocytes indicated that the primary humoral immune response to a thymus-dependent antigen was not impaired in treated rats . These results considered together indicate that metabolic formation of TFE from the anesthetic agents produced a decreased host resistance with subsequent increased susceptibility to bacterial infection . If not administered the antibiotic, the animals succumbed to the infection. Sem Hop, 1983 Sep 29, 59(34), 2381 - 7 {Role of medical treatment in spinal cord compression of tuberculous origin . Apropos of 7 cases}; Augereau B et al.; After recalling the historical background of treatment of Pott disease paraplegia, seven cases of tuberculous medullary compression treated by triple antibiotic therapy, corticosteroids and cast immobilization are reported . The diagnostic, etiologic and prognostic criteria which indicate the initiation and continuation of such treatment are defined. J Mol Biol, 1983 Sep 25, 169(3), 707 - 21 Control of expression of the Tn10-encoded tetracycline resistance genes . Equilibrium and kinetic investigation of the regulatory reactions; Hillen W et al.; The transposon Tn10-encoded TET repressor controls the expression of tetracycline resistance as well as its own synthesis . The antibiotic tetracycline functions as an inducer for both genes, which are transcribed in divergent directions from a common start area . The interaction of the TET repressor with the regulatory sequence of the tetracycline resistance operon is investigated by equilibrium and kinetic methods . The wild-type control sequence contains two nearly identical operators separated by only ten base-pairs . A deletion mutant lacking one of the operators is constructed by controlled digestion with exonuclease Bal31 . It serves to prove that the two TET operators are each occupied by a TET repressor dimer in the wild-type tet operon regulatory sequence . The association constants are approximately identical for both operators between 10(12) and 10(13) M-1 as derived from kinetic data . The half-life of the TET repressor--tet operator complex is 12 minutes when competed with tet operator DNA and two minutes when competed with the inducer tetracycline . The dissociation of the repressor--operator complex has no apparent activation enthalpy but has an activation entropy of -320 J/mol K, indicating the involvement of solvent or counterion condensation . The dissociation rate constant of the tetracycline--TET repressor complex depends strongly on temperature . The activation enthalpy is 160 kJ/mol, indicating extremely strong binding of the drug . This result is discussed with respect to the necessary sensitivity of a regulated resistance gene . The native structure of the TET repressor is a dimer, as demonstrated by molecular exclusion chromatography . The elution behavior of the TET repressor--tetracycline complex indicates clearly that the repressor--inducer complex remains a dimer . The results are discussed with respect to the regulatory functions of the components. Biochem Pharmacol, 1983 Sep 15, 32(18), 2659 - 64 Studies on gentamicin-induced labilization of rat kidney lysosomes in vitro . Possible protection by selenium; Ngaha EO et al.; The labilizing effect of gentamicin, an aminoglycoside antibiotic, on isolated rat kidney lysosomes was investigated . The light-scattering behavior of lysosomal suspensions and the release of lysosomal acid hydrolase enzymes (acid phosphatase, beta-glucuronidase and muramidase) from incubated lysosomal suspensions, in the presence of gentamicin, were used as indices of lysosomal membrane labilization . Gentamicin was found to cause a decrease in light absorbance and a release of lysosomal acid hydrolases, which indicate lysosomal membrane swelling . In the presence of selenium, in the form of potassium selenate, the decrease in light absorbance of lysosomal suspensions and the release of lysosomal acid hydrolases from isolated lysosome particles were reduced markedly . This suggests that selenium protects against gentamicin-induced lysosomal membrane labilization . The possible mechanisms of protection by selenium are discussed. Am J Physiol, 1983 Sep, 245(3), C283 - 7 Effects of insulin and tunicamycin on neuronal insulin receptors in culture; Boyd FT Jr et al.; We have examined the effect of insulin and tunicamycin, which cause decreases in cell surface insulin receptor numbers in peripheral tissues, on insulin receptors in neuron-enriched brain cell cultures . Incubation with 0.016-0.83 microM insulin for 24 h failed to decrease the specific binding of 125I-insulin in neuron-enriched cultures prepared from whole brains of 1-day-old rats . In contrast, these concentrations of insulin produced a dose-dependent decrease in the binding of 125I-insulin in fibroblastic cultures . Tunicamycin, an antibiotic which inhibits glycosylation of proteins and greatly reduced insulin binding via a reduction in apparent receptor numbers in fibroblastic cultures, caused no decrease in the binding of 125I-insulin in neuron-enriched cultures . These results indicate that brain insulin receptors are not down regulated by insulin and that glycosylation of insulin receptors may not be an important step in the regulation of their surface expression in the brain. Clin Orthop, 1983 Sep, (178), 202 - 6 An analysis of the causes of deep infection after hip and knee arthroplasties; Glynn MK et al.; Infection is a dreaded complication of joint arthroplasty . Deep infection may arise by contamination during operation, by secondary contamination of a discharging hematoma during the post-operative phase, or by the hematogenous route . Sixteen suspected cases of early and late deep infection in 1500 primary hip and knee arthroplasties performed during a ten-year period are reviewed . The operations were all performed by one of the authors (J.M.S.) in a Charnley Howarth sterile-air enclosure . No prophylactic antibiotic therapy was used, and the minimum follow-up period in all patients was one year . Suspected causes of infection were noted in six patients: the infection was considered to be hematogenous in three and to result from hematomas in two, and in the sixth patient a suspected rheumatoid cyst may have been a Brodie's abscess . Ten patients had no apparent predisposing source of infection, and breach of sterility technique was the most likely cause of infection in this group . Only two patients have required revision surgery to date . Although hematogenous infection of joint arthroplasty is possible, early, intermediate, or late infections generally are introduced during surgery either from the air or by direct contamination. Jpn J Antibiot, 1983 Sep, 36(9), 2437 - 49 {Experimental and clinical studies on latamoxef in the perinatal period}; Hayasaki M et al.; Pharmacokinetics and clinical studies on the perinatal use of latamoxef (LMOX, Shiomarin), a new parenteral oxacephem antibiotic, were carried out and the results obtained were as follows: After LMOX was intravenously given to mother at a dose of 1 g, the umbilical cord serum concentration of LMOX reached to peak with 18.4 micrograms/ml in 1 hour 20 minutes and its concentration was higher than the maternal serum after 2 hours 25 minutes and decreased gradually (T 1/2 beta = 1.61 hours) . The materno-fetal transfer of LMOX was 71.0% . LMOX showed the good transfer as well as other cephalosporins . After LMOX was intravenously administered to mother at a dose of 1 g, LMOX concentration in milk wasn't detectable up to 12 hours . LMOX was intravenously administered to 18 cases with premature rupture of membrane, at a daily dose of 2 g for 3--6 days . The prophylactic effects were observed in all cases, both mother and neonate . No adverse effects were observed in mother except for 1 case with low grade abnormality of S-GPT, transiently . We observed 3 neonates with jaundice (total bilirubin greater than or equal to 17.0 mg/dl) probably not related to LMOX . It is concluded that LMOX is less toxic, safe and clinically useful antibiotic for the treatment of perinatal infections. Jpn J Antibiot, 1983 Sep, 36(9), 2395 - 404 {Clinical application of latamoxef during the perinatal period}; Cho N et al.; Pharmacokinetic studies and clinical evaluations of latamoxef (LMOX) were carried out in perinatal mothers and infants . LMOX was promptly absorbed after intravenous injection and intravenous drip infusion in pregnant women, producing dose-related peak blood levels . Placental transference to the fetus was favorable . After intravenous injection and intravenous drip infusion of 1.0--2.0 g of LMOX, drug concentration of the cord blood, amniotic fluid and fetal blood exceeded MICs of the main pathogenic organisms . By administration of the dose of 1.0--2.0 g twice a day, it is possible to successfully prevent or treat uterine infections . LMOX was effective in the prophylaxis or therapy of perinatal infections . Moreover, newborn infants delivered from mothers receiving LMOX treatment having drug concentrations exceeded MICs of main pathogenic organisms however not remained more than 12 hours after birth, and did not exhibit any laboratory test abnormalities . The above results demonstrated that LMOX is a clinically useful antibiotic for the prophylaxis and treatment of perinatal infections. Calcif Tissue Int, 1983 Sep, 35(6), 745 - 9 IR absorption spectrophotometric analysis of the complex formed by tetracycline and synthetic hydroxyapatite; Myers HM et al.; The infrared (IR) spectra of KBr pellet preparations of tetracycline (TC) complexes with hydroxyapatite (HA) indicated that the binding of the antibiotic to bone mineral can occur independently at each of two ligands . The shifts in the IR spectrum occur for the keto-enol ligand of rings B and C and for the tricarbonylmethane grouping of ring A . Analogs that lack one or the other of these groups are able to form complexes with HA in which the common portion resembles that of the parent molecule. An Esp Pediatr, 1983 Sep, 19(3), 165 - 9 {Boutonneuse fever in childhood}; Fernandez Epifanio JL et al.; 35 cases of botonneuse Fever admitted in our hospital during the course of a year and a half are presented . They were all children between the age of 18 months and 11 years . The most common features were: fever, maculopapulous rush and "tache noir" . Weil Felix test was not of diagnostic value in one third of the cases . 71 per cent of the children recieved etiological treatment (doxicicline or cloramfenicol); the remaining 29% only got simptomatic measures . A cure was achieved in every case . Nevertheless, the manifestatios lasted longer in those not treated with antibiotic therapy. J Infect, 1983 Sep, 7(2), 134 - 8 Septicaemia and its unacceptably high mortality in the elderly; Chattopadhyay B et al.; During a period of two years the overall mortality rate among 218 patients with septicaemia was 22.4 per cent . Mortality among patients of over 60 years of age, however, was 36.6 per cent compared with only 5.1 per cent for those below that age . This difference was highly significant (P less than 0.001) . For pneumococcal septicaemia the figures were particularly disturbing, the death rate being 65 per cent for the former age group, but remaining nil for the latter . Of the 49 deaths, 44 (89.8 per cent) and five (10.2 per cent), respectively, were in those above and below that age . As death from septicaemia in the elderly seems to be unacceptably high, early institution of antibiotic therapy, even for the patient at home, is advocated so as to forestall the onset of shock . Although controversial and debatable this measure seems to be justified because it might significantly improve prognosis. Klin Padiatr, 1983 Sep-Oct, 195(5), 358 - 60 {Pseudomembranous colitis in Hirschsprung disease}; Behbehani AW et al.; Pseudomembranous colitis (PMC) is a potentially fatal complication in Hirschsprung's disease . The pathogenesis of PMC which usually takes a fulminant course, is obscure . The disease generally is associated with antibiotic therapy . We describe the clinical course and the pathological findings in a 7 1/2 months old infant with Hirschsprung's disease after surgical treatment . The pseudomembranous colitis of the patient with letal consequence is considered to be connected with antibiotic therapy. J Pharm Sci, 1983 Sep, 72(9), 1011 - 4 Quantum mechanical calculations useful for determining the mechanism of action of fosfomycin; Smeyers YG et al.; CNDO/2 calculations were performed to determine at the molecular level the mechanism of action of the antibiotic fosfomycin, (--)-(1R,2S)-(1,2-epoxypropyl)phosphonic acid . Fosfomycin, a bacterial cell wall inhibitor, is known to act as a competitive inhibitor of N-acetylglucosamine-3-O-enolpyruvyl transferase, the normal substrate of which is phosphoenolpyruvate . Both compounds were studied, and the theoretical calculations revealed that the preferred conformations of phosphoenolpyruvate and fosfomycin presented the same spatial charge distributions on the active sites, the values of which are in complete agreement with the experimental observations . These results permit the projection of some details of the receptor, with implications for the modification of fosfomycin to increase its antibiotic activity. J Antibiot (Tokyo), 1983 Sep, 36(9), 1184 - 94 Structure and conformation of saframycin R determined by high field 1H and 13C NMR and its interactions with DNA in solution; Lown JW et al.; The chemical structure and conformation of the new antitumor antibiotic saframycin R have been determined by high field 1H and 13C NMR as well as FAB mass spectrometry . Unlike other members of the saframycin family, saframycin R contains a reduced quinone ring bearing a glycolic ester moiety . Saframycin R exhibits acid promoted equilibrium and reversible covalent binding to DNA templates and, in the presence of a reducing agent, oxygen dependent single strand scission of supercoiled DNA . The extent of DNA scission is enhanced by in situ porcine carboxyl esterase or base catalyzed cleavage of the glycolic ester function plausibly by the release of the more reactive reduced saframycin A . This suggests that saframycin R may be regarded as a less toxic pro-drug for the active forms of saframycins A or S. Drug Intell Clin Pharm, 1983 Sep, 17(9), 645 - 8 Ceforanide vs . cephalothin concentrations in total joint arthroplasty; Cady WJ et al.; Total joint arthroplasty is a common orthopedic procedure and requires prophylactic antibiotic coverage to prevent infections in the operated joint . The antibiotics routinely used for prophylaxis are the cephalosporins . This study compared bone, synovial fluid, and plasma concentrations of ceforanide with cephalothin concentrations in 30 patients undergoing elective total hip or total knee arthroplasty . Ceforanide provided significantly higher plasma concentrations for 61-110 minutes postdose than did cephalothin (p less than 0.025 and p less than 0.005) . No difference was noted between the two antibiotics for the bone concentrations in the total hip arthroplasty group; however, cephalothin concentrated to a greater degree in the bone of patients undergoing total knee arthroplasty (p less than 0.05) . Cephalothin achieved higher concentrations in the synovial fluid than did ceforanide (p less than 0.05) . Both antibiotics were well tolerated and no postoperative infections were noted in either group. Biull Eksp Biol Med, 1983 Sep, 96(9), 25 - 9 {Stereological analysis of myocardial structures in plastic heart insufficiency}; Nepomniashchikh LM et al.; Electron microscopy, morphometry and stereological analysis were used to examine structural components of the myocardium of Wistar rats after injection of the anthracycline antibiotic rubomycin . Using the determination of absolute summary weights of cardiomyocytes, interstitial connective tissue, vessels and intercellular space as well as of the volume and surface densities of these structures the development of involutional atrophic lesions in the myocardium was demonstrated . The connective tissue showed an increase in the population of fibroblasts, diffuse activation of protein synthesis in them and collagen synthesis de novo . The genetic relationship between abnormal regeneration of cardiomyocyte ultrastructure (plastic heart insufficiency) and diffusive cardiosclerosis is established. Arch Surg, 1983 Sep, 118(9), 1091 - 4 Roux-en-Y on-line intussusception to avoid ascending cholangitis in biliary atresia; Donahoe PK et al.; A child with biliary atresia experienced severe ascending cholangitis when the exteriorized loop of a portahepatoenterostomy was internalized . Backwash of bowel contents was reduced and further cholangitis was prevented by creation of an on-line intussuscepted Roux-en-Y jejunal loop to provide a nonrefluxing conduit from the porta hepatis . The loop could then be internalized and antibiotic therapy could be discontinued . The success of this procedure in this case encourages us to use this method in similar cases of biliary atresia . It may be of use in all Roux-en-Y loops, such as those used to drain the transplanted liver of patients with biliary atresia and those created to drain the distal part of the transplanted pancreas. Jpn J Antibiot, 1983 Sep, 36(9), 2474 - 93 {Experimental and clinical evaluation of cefotetan in obstetrics and gynecology} {Evaluation of cefotetan in obstetrics and gynecology} Yasuda J, Yamamoto T, Itoh M, Honjo H, Okada H, Kanao M. Fundamental and clinical studies on gynecological use of cefotetan (CTT), a new cephamycin antibiotic, were performed with following results . Following the intravenous administration of 2.0 g of CTT, T 1/2 beta in serum was 3.1 hours and longer than the previous cephamycin antibiotics . The yields of CTT from serum to various uterine tissues and discharge from retroperitoneum were about 30 approximately 50% . In clinical use, 14 patients with gynecological infections were administrated CTT, and it showed excellent or good efficacy in all patients . No side effects were noted except 1 transient disturbance in liver function. Jpn J Antibiot, 1983 Sep, 36(9), 2450 - 4 {Clinical effect of cefotetan against infectious diseases in obstetrics and gynaecology}; Chimura T et al.; Clinical study on cefotetan (CTT), a new cephamycin antibiotic, was carried out and the following results were obtained . CTT was intravenously administered at a daily dose of 2 to 4 g to 24 cases including 10 cases with intrauterine infection, 2 cases with adnexitis, 6 cases with intrapelvic infection and 6 cases with extragenital infection . Marked response was seen in 8 cases, moderate response in 15 and no response in 1 . Neither side effects nor abnormal values in clinical laboratory tests were observed. Acta Anaesthesiol Belg, 1983 Sep, 34(3), 179 - 89 Cost evaluation of infections in intensive care; de Clercq H et al.; The study deals with one aspect of cost benefit analysis of infection control, namely the measurement of extra costs incured by patients who acquired nosocomial infections (NI) in intensive care units (ICU) . The consequences of NI are expressed in terms of length of stay, extra drug and antibiotic costs, extra sterile supply used and mortality . Infected patients stayed at the ICU twice as long as non - infected patients, the mean cost of antibiotics prescribed was four times higher, the mean value of other drugs and infusion fluids was approximately 1 1/2 times higher . Three methods for measuring cost are compared: the physician's assessment method, comparison of infected patients with all non - infected patients and matched control analysis. Naunyn Schmiedebergs Arch Pharmacol, 1983 Sep, 324(1), 58 - 63 Effect of phytohemagglutinin-stimulated human lymphocytes on isolated rat atria . Participation of lipoxygenase products of arachidonic acid metabolism; Sterin-Borda L et al.; The effect of phytohemagglutinin (PHA) stimulated human lymphocytes on the contractile activity of isolated rat atria was studied . Increased isometric developed tension (IDT) and higher frequency of contractions (FC) were observed shortly after contact of PHA-activated lymphocytes with spontaneously beating rat atria . Since pre-exposure of the lymphocytes to PHA was not necessary and the pharmacologic effects were demonstrated immediately after addition of the lectin, division of the effector cells as a requisite for their action was excluded . Experiments performed with the antibiotic crystallized from Streptomyces chartreusenis, Ca2+-ionophore A-23187, yielded similar effects . Lymphocyte fractionation studies showed that T-lymphocyte-rich and T-lymphocyte-depleted cell fractions had opposite effects on IDT and FC . The inotropic and chronotropic effects were not modified by (-)-propranolol or antihistaminics . Inhibitor of the synthesis of prostaglandins enhanced the action of PHA-activated lymphocytes but inhibitors of the lipoxygenase pathway: 5,8,11,14-eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) prevented the increment of IDT and FC . Also, FPL55712, an antagonist of SRS-A abolished the positive inotropic and chronotropic effects of PHA-activated lymphocytes on rat atria . Therefore, a central role for SRS-A in this reaction is suggested. Am J Hosp Pharm, 1983 Sep, 40(9), 1483 - 8 Hospital survival strategies for the 1980s; Bonney RS; Survival strategies for hospitals and hospital pharmacy departments are presented, and one hospital's development into a health-services system is described . Financial and competitive pressures are forcing institutions to develop new strategies for survival . The primary institutional strategy is diversification--both horizontal and vertical . Diversification can assist in the hospital's growth, increase its asset and revenue bases, and lead to the development of a health-care delivery system . Marketing to physicians and developing information systems are also critical strategies under a prospective payment system . Institutions will need to know the cost of providing care for specific diagnosis-related groups . Strategies must be employed to develop incentives to reduce inpatient acute-care services and to increase productivity . Physicians should be involved in all of the institutional strategies . Strategies for the pharmacy department are basically the same . Pharmacy departments should develop programs to reduce drug use (especially antibiotic use) and information systems that show the actual cost of providing services by diagnosis . The major corporate restructuring and diversification efforts of one hospital are described . The future of hospitals and pharmacy departments will depend on the successful application of the strategies discussed. Public Health Rep, 1983 Sep-Oct, Suppl, 97 - 106 Health protection: Surveillance and control of infectious diseases; Freeze-fracture studies of photoreceptor membranes: new observations bearing upon the distribution of cholesterol; We performed electron microscopy of replicas from freeze-fractured retinas exposed during or after fixation to the cholesterol-binding antibiotic, filipin . We observed characteristic filipin-induced perturbations throughout the disk and plasma membranes of retinal rod outer segments of various species . It is evident that a prolonged exposure to filipin in fixative enhances rather than reduces presumptive cholesterol detection in the vertebrate photoreceptor cell . In agreement with the pattern seen in our previous study (Andrews, L.D., and A . I . Cohen, 1979, J . Cell Biol., 81:215-228), filipin-binding in membranes exhibiting particle-free patches seemed largely confined to these patches . Favorably fractured photoreceptors exhibited marked filipin-binding in apical inner segment plasma membrane topologically confluent with and proximate to the outer segment plasma membrane, which was comparatively free of filipin binding . A possible boundary between these differing membrane domains was suggested in a number of replicas exhibiting lower filipin binding to the apical plasma membrane of the inner segment in the area surrounding the cilium . This area contains a structure (Andrews, L . D., 1982, Freeze-fracture studies of vertebrate photoreceptors, In Structure of the Eye, J . G . Hollyfield and E . Acosta Vidrio, editors, Elsevier/North-Holland, New York, 11-23) that resembles the active zones of the nerve terminals for the frog neuromuscular junction . These observations lead us to hypothesize that these structures may function to direct vesicle fusion to occur near them, in a domain of membrane more closely resembling outer than inner segment plasma membrane . The above evidence supports the views that (a) all disk membranes contain cholesterol, but the particle-free patches present in some disks trap cholesterol from contiguous particulate membrane regions; (b) contiguous inner and outer segment membranes may greatly differ in cholesterol content; and (c) the suggested higher cholesterol in the inner segment than in the outer segment plasma membrane may help direct newly inserted photopigment molecules to the outer segment. J Bacteriol, 1983 Sep, 155(3), 1219 - 23 Localized hydroxylamine mutagenesis, and cotransduction of threonine and lysine genes, in Streptomyces venezuelae; Stuttard C; A lysate of the generalized transducing phage SV1, grown on the prototrophic type strain 10712 of Streptomyces venezuelae, was mutagenized with hydroxylamine and used to transduce a lysineless auxotroph to lysine independence on supplemented minimal agar . A complex threonine mutant, strain VS95, was isolated from among the transductants and was shown to be carrying at least two different thr mutations . These were about 50% cotransducible with alleles of four independently isolated lysA mutations, as were two other independently isolated threonine mutations, thr-1 and hom-5 . The location of thr genes close to lysA occurs in at least three other streptomycetes, but apparently not in Streptomyces coelicolor A3(2), in which the lysA and thr loci are at diametrically opposite locations on the linkage map . This first observation of cotransduction between loci governing the biosynthesis of different amino acids in the genus Streptomyces demonstrates the feasibility of fine-structure genetic analysis by transduction in these antibiotic-producing bacteria. Hosp Pract (Off Ed), 1983 Sep, 18(9), 175 - 9, 183-4 Neonatal meningitis: problems and prospects; Feigin RD; Even with the best antibiotic therapy, prognosis remains grim . The chance of successful outcome can be enhanced by techniques that provide speedy and accurate diagnosis and bolster the defensive capabilities of the neonatal immune system . Early trials of such strategies are encouraging . Some of these approaches are now applicable in selected patients. Yale J Biol Med, 1983 Sep-Dec, 56(5-6), 397 - 403 Transbilayer distribution of sterols in mycoplasma membranes: a review; Bittman R et al.; The polyene antibiotic, filipin, binds to 3 beta-hydroxysterols . The initial rate of filipin-sterol association, monitored in a stopped-flow spectrophotometer, was first order in each reacting partner . The ratio of rate constants in intact mycoplasma cells relative to isolated, unsealed membranes provides an estimate of sterol distribution in the membrane bilayer . Cholesterol is distributed symmetrically in the bilayer of M . gallisepticum cells from the early exponential phase . However, in the M . capricolum membrane two-thirds of the unesterified cholesterol is localized in the outer leaflet; alkyl-sterols are distributed predominantly in the external monolayer . Cholesterol is translocated rapidly in the bilayer of M . capricolum cells . Exogenous phospholipids incorporated into the membrane had no effect on the cholesterol distribution in M . capricolum. Plasmid, 1983 Sep, 10(2), 184 - 95 Instability of a high-copy-number mutant of a miniplasmid derived from broad host range IncP plasmid RK2; Thomas CM; Mini-RK2 plasmids pCT460 and pCT461 which contain the oriVRK2, trfA and trfB regions of RK2 in addition to tetracycline and kanamycin resistance determinants, have copy numbers of 17 and 35 copies per chromosome equivalent, respectively . The difference in copy number is due to a 56-bp deletion in oriVRK2 in pCT461 . In Escherichia coli only pCT461 is markedly unstable in batch culture while both are unstable (although pCT461 is more so) in bacteria on stock plates . The instability of pCT461 in bacteria on stock plates is recA+ dependent and appears to involve loss of plasmid DNA from bacteria rather than selective cell death . After storage of recA+ bacteria carrying pCT461 for a few weeks the remaining antibiotic-resistant bacteria carry a mixture of plasmid DNA species including parental pCT461, transposable element insertion derivatives, and, by far the majority, deletion derivatives . It appears that one particular plasmid region, which includes the kilD gene (which inhibits plasmid maintenance in the absence of korD which, however, is present on pCT460 and pCT461), is responsible for this instability in a gene dosage-dependent way . Most of these deletion derivatives are dependent on pCT461-specified trfA gene (essential for replication) so that they do not displace pCT461 entirely . Their presence reduces the copy number of pCT461, thus reducing the instability, and is probably ultimately responsible for pCT461 survival on stock plates . In many bacteria the same process which gives rise to deletion derivatives may result in degradation of plasmid DNA extensive enough to cause loss of pCT461. JOGN Nurs, 1983 Sep-Oct, 12(5), 327 - 31 Managing drug interactions with oral contraceptives; Stoehr GP et al.; PIP: Drus interactions involving oral contraceptives (OCs) are of increasing concern . Antitubercular drugs, anticonvulsants, and antibiotics are among the drugs believed to alter the efficacy of OCs . Rifampin, for example, appears to induce an increase in the rate of metabolism of OCs, resulting in unacceptable rates of breakthrough bleeding and pregnancy . Phenobarbital stimulates the liver's drug metabolizing enzymes and may alter the disposition of some progestogens by increasing their binding affinity to plasma proteins . In addition, OCs may affect the activity of certain drugs and vitamins, including anticoagulants, vitamin B6, and folic acid . Conscientious family planning nurse practitioners can play an important role in the management of these drug interactions . OC users who require antibiotic therapy should be monitored for signs of diminished estrogen effect . Women receiving anticoagulants should be monitored when OCs are either begun or discontinued, and weekly or twice weekly determinations of prothrombin time may be required . Significant drug interactions may indicate the need for another means of contraception . Effective contraceptive counseling in such cases requires a sympathetic approach and a review of alternate contraceptive methods . Techniques of insertion, known side effects, and noncontraceptive benefits should be discussed . Patients who are switched to another OC preparation should be instructed to report breakthrough bleeding . Family planning nurse practitioners, especially those working with very young or low income women, should stress the need for adequate nutrition . In some cases, nutritional supplements may be indicated . In addition, patients should be instructed to question other health care providers about possible interactions with OCs whenever drug therapy is prescribed . J Infect Dis . 1983 Sep;148(3):611. Suppression of the production of migration inhibitory factor in humans by tetracycline; Ganguly R et al.; The role of Tc in the suppression of immunity has not been widely evaluated although this antibiotic is often prescribed as a long-term therapy {1} . Sporadic reports have indicated that Tc suppresses cellular immunity {2} . However, no data are available concerning the effects of Tc on lymphokine production, especially in human subjects . Peripheral blood mononuclear cells (2 X 10(6)/ml) were obtained from seven normal volunteers and pulsed with 150 micrograms of con A/ml of medium for 3 hr at 37 C . The procedure was carried out in the presence or absence of Tc in RPMI medium under an atmosphere of 5% CO2 . The cells were then pelleted, washed, and resuspended in RPMI medium with or without similar concentrations of Tc . Following incubation for 48 hr, the cells were removed and the supernatant was assayed for MIF activities with the use of guinea pig peritoneal macrophages as indicator cells . A change of greater than or equal to 20% in migration was considered significant {3} . Remarkable inhibition of MIF production was noted in cells obtained from five of seven volunteers in the presence of 3 micrograms and 100 micrograms of Tc/ml . ConA-induced inhibition of migration was almost abolished in cell cultures in the presence of 3 micrograms of Tc/ml . Negative inhibition (accelerated migration) was observed in the presence of 100 micrograms of Tc/ml . Macrophage migration in the presence of 100 micrograms of Tc/ml was greater than the migration of control cells . Thus, it appeared that Tc not only interfered with MIF production but also modulated factors involved in the control of normal cell migration.(ABSTRACT TRUNCATED AT 250 WORDS) Infect Immun, 1983 Sep, 41(3), 931 - 4 An outbreak of gastroenteritis due to a heat-labile enterotoxin-producing strain of Escherichia coli; Wood LV et al.; In April 1981, an outbreak of gastroenteritis, characterized by diarrhea and abdominal cramps, occurred in 282 of approximately 3,000 personnel at a large metropolitan hospital in San Antonio, Tex . There was a significant association between illness and eating at the hospital cafeteria (P = 0.0008), but no specific food could be incriminated . Stools or rectal swabs from 54 ill individuals produced almost pure cultures of Escherichia coli . Cultures from 51 of these subjects had identical antibiotic sensitivity patterns, and 38 had the same biotype . Isolates from 45 persons were tested for production of heat-stable and heat-labile enterotoxins, using the suckling mouse and Y-1 adrenal cell assays, respectively . Of 45 isolates, 41 produced heat-labile enterotoxins, while 0 of 45 produced heat-stabile enterotoxins . Two isolates were rough, and 34 of the remaining 43 were serotype O25:H- . Two strains were O25:H+ . None of the 45 strains possessed hemagglutination patterns typical of colonization factor antigens I or II . Six of seven O25:H- heat-labile enterotoxin-positive strains selected at random were piliated as seen by electron microscopy but did not agglutinate with anti-colonization factor antigens I or II antisera. J Gen Physiol, 1983 Sep, 82(3), 297 - 329 Basolateral potassium channel in turtle colon . Evidence for single-file ion flow; Kirk KL et al.; Treatment of the apical surface of the isolated, ouabain-inhibited turtle colon with the polyene antibiotic amphotericin B permitted the properties of a barium-sensitive potassium conductance in the basolateral membrane to be discerned from the measurements of transepithelial fluxes and electrical currents . Simultaneous measurements of potassium currents and 42K fluxes showed that the movement of potassium was not in accord with simple diffusion . Two other cations, thallium and rubidium, were also permeable and, in addition, exhibited strong interactions with the potassium tracer fluxes . The results indicate that permeant cations exhibit positive coupling, which is consistent with a single-file mechanism of ion translocation through a membrane channel. Proc Natl Acad Sci U S A, 1983 Sep, 80(18), 5607 - 11 Amphotericin B selection of mutant Chinese hamster cells with defects in the receptor-mediated endocytosis of low density lipoprotein and cholesterol biosynthesis; Krieger M et al.; This paper describes a rapid and efficient two-step procedure for the isolation of mutant cells with defects in receptor-mediated endocytosis . The procedure takes advantage of two fungal metabolites, compactin (ML236B), a potent inhibitor of cholesterol biosynthesis, and amphotericin B, a polyene antibiotic that forms toxic complexes with sterols in membranes . Mutagen-treated Chinese hamster ovary cells were preincubated overnight in a medium containing mevalonate, low density lipoprotein (LDL), and compactin (Mev/LDL/Com) . At the end of the preincubation period, wild-type cells were cholesterol replete while mutant cells that could not utilize the cholesterol in LDL were cholesterol deficient . Subsequent incubation with amphotericin B for 6 hr killed most of the wild-type cells . After a second round of Mev/LDL/Com-amphotericin B selection, endocytosis-defective clones appeared at a frequency of approximately equal to 2.6 X 10(-5) . Some of these clones expressed LDL receptor-defective phenotypes and fell into one of two previously defined classes of mutation . Sensitivity of the mutants to infection by vesicular stomatitis virus suggested that the mutations do not disrupt the coated pit-coated vesicle pathway of endocytosis . Minor modifications in the Mev/LDL/Com-amphotericin B selection permit the isolation of cholesterol auxotrophs and might allow the isolation of conditional-lethal mutations . Because LDL can be coupled to ligands that bind to receptors other than the LDL receptor, Mev/LDL/Com-amphotericin B selection may permit the isolation of mutant cells with defects that specifically disrupt other endocytic pathways. Obstet Gynecol, 1983 Sep, 62(3 Suppl), 67s - 69s Necrotizing fasciitis following diagnostic laparoscopy; Sotrel G et al.; A case of necrotizing fasciitis of the abdominal wall, following an uneventful diagnostic laparoscopy in an elderly, diabetic patient is reported . The patient recovered after extensive surgical debridement and antibiotic therapy . The possibility of a lethal infection in patients with impaired immune defense mechanisms is discussed. Ann Trop Paediatr, 1983 Sep, 3(3), 137 - 42 A prospective survey of gingivitis in Keneba, a rural West African community; Lamb WH et al.; The prevalence and severity of gingivitis was studied in 204 children living in a rural West African community . Seasonal prevalence varied from 38.6% to 9.5% . The lowest prevalence coincided with the seasonal consumption of citrus fruits and mangoes . Prevalence increased with age . Of the children, 13.7% required treatment with a standard antibiotic regime for severe gingivitis . Severe gingivitis occurred frequently in children under three years of age and in females . There was no clear relationship between the prevalence of gingivitis and malnutrition as assessed by anthropometric indices obtained from the children . Findings in this study suggest that measures to improve oral hygiene is the intervention most likely to reduce the prevalence of gingivitis. Antibiotiki, 1983 Sep, 28(9), 686 - 9 {Characteristics of 57Co-bleomycetin accumulation in the primary tumor and in its metastases to the lungs in mice with Lewis carcinoma}; Vatin OE et al.; Distribution of 57Co-bleomycin was studied in mice with Lewis carcinoma implanted into different parts of the body . It was found that organ distribution of the labeled antibiotic did not depend on the tumor localization . The accumulation level of 57Co-bleomycin in Lewis carcinoma implanted subcutaneously into the pad foot was 3 times higher than that in the healthy pad . Resection of the primary tumor stimulated metastasis to the lungs resulting in relatively selective accumulation of the antibiotic in the lungs . The levels of 57Co-bleomycin in the lungs the main part of which was affected with metastases were 3--7 times higher than the respective control values. Urologe A, 1983 Sep, 22 Suppl, 322 - 4 {Bleomycin in the treatment of squamous cell carcinoma of the penis and bladder}; Rathert P; Bleomycin is an antineoplastic antibiotic with special effects on squamous cell carcinomas . Penile carcinomas in early stages may be treated with good early results by Bleomycin alone . In contrast to the normal course of penile carcinomas late recurrences and metastases may develop even after an interval of more than seven years . Therefore the monotherapy with Bleomycin is no longer recommended . The effects of Bleomycin on squamous cell carcinomas of the bladder are disappointing . The new therapeutic approach with Bleomycin and hyperthermia of the bladder may give better results. Res Vet Sci, 1983 Sep, 35(2), 200 - 5 Cross immunity between strains of Cowdria ruminantium; Uilenberg G et al.; Cross immunity tests with strains of Cowdria ruminantium from South Africa, the Sudan, Sao Tome and Nigeria failed to demonstrate antigenic differences . The antibiotic ampicillin showed no activity against heartwater. Mol Biol (Mosk), 1983 Sep-Oct, 17(5), 1019 - 27 {Location of RNA-dependent DNA polymerase within the endogenous template complex and discrimination of RNA- and DNA-dependent synthesis of DNA in Escherichia coli cells by alkylating dTTP gamma-amide}; Grabkina OA et al.; These data demonstrate that actinomycin D inhibits only 75-80% of DNA synthesis in cells of E . coli treated by lysozyme and ethyl enediaminetetraacetate . The residual synthesis is not the result of untemplated polymerization of dNTP . The DNA synthesis in spheroplasts does not correlate with replication of chromosomal DNA of E . coli catalyzed by DNA polymerase III sensitive to sulfhydryl blocking agents . N-ethylmaleimide does not inhibit this synthesis . No ATP stimulation of DNA synthesis is observed . The enzyme(s) responsible for DNA synthesis on endogenous template is (are) concentrated in interphase (D-fraction) as revealed by high speed centrifugation of spheroplasts lysate and they are absent in the chromosomal DNA fraction . dTTP 4-(N-2-chloroethyl-N-mehylamino) benzylamide suppresses completely the insensitive to actinomycin D action DNA synthesis and practically does not act on the sensitive one . It is suggested, that the DNA synthesis stable to the action of the antibiotic is catalyzed by RNA dependent DNA polymerase. J Hosp Infect, 1983 Sep, 4(3), 279 - 84 Latamoxef for the prophylaxis of abdominal surgical wound infection: a controlled clinical trial; Ausobsky JR et al.; In a series of 236 abdominal operations, patients were allocated at random to receive a single intravenous dose of either 1 g cephaloridine or 1 g latamoxef (at induction of anesthesia) for the prophylaxis of postoperative wound infection . Of the 116 patients given latamoxef, one developed major and seven minor wound infections, whereas five major and 21 minor infections occurred in the cephaloridine group (P less than 0.01) . Latamoxef has now replaced cephaloridine as our prophylactic antibiotic of choice in potentially contaminated abdominal operations. J Antibiot (Tokyo), 1983 Sep, 36(9), 1216 - 21 Antitumor activity of trioxacarcin C; Fujimoto K et al.; The novel antitumor antibiotic<