Am J Med, 1985 Jun 7, 78(6A), 113 - 6 Multiple-dose study of imipenem/cilastatin in patients with end-stage renal disease undergoing long-term hemodialysis; Berman SJ et al.; Multiple doses of imipenem/cilastatin were administered to patients with end-stage renal disease undergoing long-term hemodialysis . Schedules of 250 mg every six hours, 500 mg every six hours, and 500 mg every 12 hours were studied . Five hundred mg every 12 hours was the most efficient schedule that maintained effective trough antibiotic activity . Twelve volunteers including two patients with clinical infections using the dose schedule of 500 mg every 12 hours received imipenem/cilastatin for two to 14 days without any notable clinical side effects . Imipenem peak and trough concentrations averaged 29 +/- 5 micrograms/ml and 10 +/- 3 micrograms/ml, respectively . No accumulation of imipenem occurred during the trial . Cilastatin peak and trough concentrations were 89 +/- 38 micrograms/ml and 70 +/- 27 micrograms/ml, respectively . The plasma concentration of cilastatin increased with each dose until the next hemodialysis session. J Otolaryngol, 1985 Jun, 14(3), 197 - 200 Frontal sinusitis--a 10 year experience; Middleton WG et al.; Frontal sinusitis follows upper respiratory infections, sinus trauma, and swimming . Complications, often life threatening, still occur although less frequently than in the pre-antibiotic era . The course of 40 patients admitted to St . Michael's Hospital with a diagnosis of frontal sinusitis between the years 1973-83 is reviewed . The regional complications as well as the surgical procedures required to manage these problems are discussed . The osteoplastic flap with obliteration of the sinus cavity by osteoneogenesis has become the procedure of choice in dealing with most cases of chronic frontal sinusitis. Br J Radiol, 1985 Jun, 58(690), 537 - 42 A device for interstitial therapy of low pelvic tumours--the Hammersmith perineal hedgehog; Branson AN et al.; The freehand production of accurate volume or multiplane implants for interstitial therapy is difficult . The size of tumour that may be treated in this fashion is therefore limited . A solution to this problem is to use a perspex template to guide the implant and maintain its configuration during treatment . We describe our experience using such a template (the Syed-Neblett template) in treating pelvic tumours . The device has been adapted for use with the iridium wire available in the UK . Two new templates have been designed which are more versatile for treating tumours in this area . Ten patients have been treated and with appropriate analgesia, antibiotic cover and nursing care the implant was well tolerated. Hinyokika Kiyo, 1985 Jun, 31(6), 1071 - 5 {A case of Fournier's gangrene requiring extensive debridement including bilateral orchiectomy and amputation of the penis}; Oki M et al.; With the evolution of antibiotic agents, necrotizing fasciitis of the male genitalia first described by Fournier has become rare . However, its mortality rate is still high . We present a severe case of this disease . An 80-year-old man who had poor controlled diabetes mellitus was admitted to our hospital with painful swelling of penoscrotal region . Chemotherapy using broad-spectrum antibiotics and drainage of penis, scrotum and lower abdominal wall was performed combined with insulin therapy . Despite the drainage and aggressive chemotherapy with insulin therapy, the gangrene enlarged rapidly and the patient's general condition was getting very poor . Then, we performed extensive debridement including bilateral orchiectomy and amputation of the penis . After the operation, the patient became afebrile and his general condition was improved. Int J Pept Protein Res, 1985 Jun, 25(6), 580 - 4 Synthesis of protected peptides with the sequence 8-13-1-3 and 4-13-1-3 of mycobacillin and their analogs; Mladenova-Orlinova LV et al.; We have synthesized both a protected nonapeptide of the mycobacillin 8-13-1-3 amino acid sequence and a protected tridecapeptide of the 4-13-1-3 sequence, which are a fragment and a open chain analog of this antibiotic, respectively . Some of their analogs with a reversed configuration of the amino acids at fixed positions have also been synthesized . The nonapeptides were obtained by coupling partially protected mycobacillin fragments with the sequence 8-10 and 11-13-1-3 while the tridecapeptides were synthesized by coupling partially protected fragments 4-7 and 8-13-1-3 . Configuration analogs of these fragments were also used . The coupling methods applied were DCCI/HONSu or DCCI/HOBt . The purification of the synthesized peptides was achieved by means of recrystallization or column chromatography on silica gel . They were characterized mainly by m.p., degree of optical rotation, elemental and amino acid analysis. Antimicrob Agents Chemother, 1985 Jun, 27(6), 974 - 6 Self-induced nystatin resistance in Dictyostelium discoideum; Kasbekar DP et al.; The cellular slime mold Dictyostelium discoideum is normally susceptible to the action of the polyene antibiotic nystatin . We describe conditions under which transient nystatin resistance can be induced in the absence of detectable changes in sterol composition . These results suggest that nystatin plays a positive role in promoting resistance to itself. J Antibiot (Tokyo), 1985 Jun, 38(6), 746 - 52 CC-1065 transformations; Martin DG et al.; This report defines the transformations that antitumor antibiotic CC-1065 underwent under basic and acidic conditions . The isolation, purification, characterization, and biological properties of a cyclopropapyrroloindole fragment, and an acidic fragment, PDE-I dimer, from a mild alkaline fragmentation and the phenolic product, AAP, resulting from alkylation of acetic acid by the cyclopropyl function are described. Carcinogenesis, 1985 Jun, 6(6), 945 - 7 Unscheduled DNA synthesis induced by streptonigrin in ataxia telangiectasia fibroblasts; Taylor AM et al.; Streptonigrin is an antitumour antibiotic, which at low doses produces DNA strand breaks in cultured cells leading, e.g., to decreased colony-forming ability and decreased rates of DNA synthesis . At higher doses the drug can induce unscheduled DNA synthesis (UDS) presumably as a consequence of excision of large DNA adducts . Ataxia telangiectasia (A-T) cells are unusually sensitive to streptonigrin, but we show here that they can perform excision repair, as demonstrated by UDS, at the same level as normal cells following exposure to the drug . This result suggests that of the apparent two modes of action of streptonigrin it is the DNA strand-breaking capacity to which A-T cells are unusually sensitive . This is consistent with previous reports suggesting some form of DNA strand break in A-T cells is deficiently repaired. Am Rev Respir Dis, 1985 Jun, 131(6), 880 - 5 The role of fiberoptic bronchoscopy in the evaluation of immunocompromised hosts with diffuse pulmonary infiltrates; Williams D et al.; To define the utility of fiberoptic bronchoscopy in the evaluation of immunocompromised patients with diffuse pulmonary infiltrates, we reviewed our experience between January 1980, and January 1983, with 50 such patients with a wide variety of underlying diseases . Of these, 35 patients underwent bronchoscopy, including brushings, alveolar lavage, and transbronchial biopsy, and 15 underwent open lung biopsy; 8 patients underwent both procedures . All patients with a nondiagnostic bronchoscopy either recovered without specific antibiotic therapy or underwent an open procedure . A diagnosis was made in 29 patients (58%) . An infectious process was found in 20 patients (40%) . A diagnosis was made bronchoscopically in 19 patients including 18 infections . Transbronchial biopsy was rarely diagnostic of infection when brushings were negative . For all diagnoses, bronchoscopy had a sensitivity of 76.9% . For all pulmonary infections, bronchoscopy had a sensitivity of 90% . Given a negative bronchoscopy, the probability that an infection was not present (i.e., predictive value negative) was 94.4% . Unfortunately, making a specific diagnosis did not appear to greatly improve survival . We conclude that in this setting: (1) fiberoptic bronchoscopy is an extremely sensitive procedure for diagnosing pulmonary infections, (2) bronchial brushings are as useful as transbronchial biopsies for diagnosing nonfungal infections, (3) these procedures are less useful for diagnosing noninfectious conditions, and (4) in the face of a negative bronchoscopic procedure, there is a very low probability that an infectious process will be found with an open biopsy. Am J Gastroenterol, 1985 Jun, 80(6), 472 - 8 Amebic liver abscess: a study of 11 cases compared with a series of 38 patients with pyogenic liver abscess; Greenstein AJ et al.; Amebic liver abscess is an uncommon disease in the northern states of North America with 11 cases seen among approximately 500,000 Mount Sinai Hospital admissions over a 16-year period . Five of 11 cases originated in, or had recently visited South America . In three of these, and two patients with concomitant intestinal amebiasis, the diagnosis was suspected on admission . Diagnosis after admission was rapid, mean 5 days, compared with a mean of 13 days in pyogenic liver abscess . There was a higher incidence of male patients, nine males versus two females which was greater than the excess found in our pyogenic abscesses, 22 versus 16 . Multiplicity was less common than in pyogenic abscess, 27 versus 50%, respectively . All three patients with multiple abscesses survived with surgical drainage and antibiotic therapy despite numerous complicating factors, including secondary bacterial infection . One patient resolved with drug treatment only; all others were treated with drugs and concomitant drainage; surgical drainage in earlier cases, and percutaneous drainage more recently . There was a single postoperative death . Drug treatment is the first therapeutic modality, and if recovery is delayed more than 2 days percutaneous aspiration should be carried out . This was successful in four cases . Surgery should seldom be required with present methods of accurately localizing amebic liver abscess, but is essential for ruptured abscess with peritonitis, and liver abscess with associated intestinal problems such as toxic megacolon, colonic perforation, or fulminating colitis . There has been a significant reduction in mortality of amebic liver abscess over the past 50 years and particularly within the past decade.(ABSTRACT TRUNCATED AT 250 WORDS) Chest, 1985 Jun, 87(6), 840 - 2 Bronchiolitis obliterans caused by Legionella pneumophila; Sato P et al.; A diabetic patient presented with symptoms and laboratory findings compatible with atypical pneumonia . Despite appropriate antibiotic therapy, his dyspnea, arterial oxygenation, and chest roentgenographic findings worsened . Because the patient had a history of homosexual contact, an open lung biopsy was obtained to morphologically define the tissue reaction and to search for a specific etiology . Histologic examination showed bronchiolitis obliterans but did not demonstrate a cause . Legionnaires' disease was subsequently diagnosed on the basis of a fourfold rise in indirect fluorescent antibody titer . This case report demonstrates that Legionella pneumophila may induce lung injury with bronchiolitis obliterans . Such patients may benefit from corticosteroid treatment. Chest, 1985 Jun, 87(6), 731 - 4 Utility of pneumonotomy in the treatment of cavitary lung disease; Snow N et al.; Three patients were judged to be prohibitive operative risks despite the need for urgent drainage of cavitary pulmonary lesions . Cavernostomy was performed in each case, with a satisfactory long-term outcome in two patients . The third patient recovered from his pulmonary insult, but died much later, secondary to an unrelated illness . One patient had a purulent lung abscess due to aspiration, one had atypical tuberculosis resistant to all antibiotics, and the third patient experienced massive hemoptysis from a tuberculous cavity . Two-stage procedures were utilized in the first two patients, while urgent operation in the third patient was facilitated by adhesions from a previous thoracotomy and pleural infection . Care must be taken to minimize endobronchial and pleural contamination by meticulous attention to detail during the performance of percutaneous tube drainage . There are relatively few indications for percutaneous drainage of cavitary pulmonary lesions in this antibiotic era . However, certain clinical situations should prompt consideration for a pneumonotomy . These include a severely septic or debilitated patient who is unresponsive to medical management, the presence of resistant pathogens in a compromised host, and the presence of severe adhesive pleuritis which may prohibit an expeditious thoracotomy and resection for massive hemoptysis. J Gen Microbiol, 1985 Jun, 131 ( Pt 6), 1279 - 87 Characterization and regulation of p-aminobenzoic acid synthase from Streptomyces griseus; Gil JA et al.; p-Aminobenzoic acid synthase (PABA synthase) of Streptomyces griseus catalyses the conversion of chorismic acid to p-aminobenzoic acid (PABA), a precursor of the aromatic p-aminoacetophenone moiety of candicidin, a polyene macrolide antibiotic . This enzyme uses glutamine or ammonia as amino donors for PABA formation . Enzyme extracts converted {14C}chorismic acid to labelled PABA . PABA synthase was present in S . griseus IMRU 3570 only during the antibiotic producing phase . No detectable levels of the enzyme were found in cell-free extracts of nonproducing mutants of S . griseus obtained after UV mutagenesis . PABA synthase activity was found also in Streptomyces coelicolor var . aminophilus, producer of the polyene macrolide antibiotic fungimycin, but it was not present in extracts of several other streptomycetes that do not produce aromatic polyene macrolide antibiotics . PABA synthase (amidotransferase) activity was partially purified by DEAE-Bio-gel and Sephacryl S-200 filtrations . The estimated molecular weight was 50000 . PABA synthase was repressed by aromatic amino acids and PABA but not by anthranilic acid . Inorganic phosphate strongly repressed but did not inhibit PABA synthase activity. Exp Cell Res, 1985 Jun, 158(2), 493 - 9 Involvement of plasma membrane glycoproteins in the contact-dependent inhibition of growth of human fibroblasts; Wieser RJ et al.; The human embryonal lung fibroblasts used in this study showed a pronounced inhibition of growth when reaching a critical cell density . This effect has been mimicked by the addition of glutaraldehyde-fixed human fibroblasts to sparsely seeded growing cells . Inhibition of growth was not observed when glutaraldehyde-fixed cells were pretreated with galactosidase or with galactose-specific lectins, or when glutaraldehyde-fixed human or rabbit erythrocytes were added to the proliferating fibroblasts . In addition, glutaraldehyde-fixed mitotic cells were without effect on the proliferation, while cells prepared from sparse culture had lesser potency than cells prepared from confluent cultures . Plasma membranes, isolated from cells of confluent cultures, when added to growing cultures of human fibroblasts inhibited DNA synthesis in a concentration-dependent manner . On the other hand, plasma membranes isolated from sparsely seeded cells had only minor inhibitory potency . When the plasma membranes were isolated from cells treated previously with tunicamycin, an antibiotic which inhibits the synthesis of the oligosaccharide portion of asparagine-linked glycoproteins, the inhibitory effect was abolished . The same effect was observed when plasma membranes were pretreated with galactosidase . These data indicate that the growth of cells in vitro is regulated by specific cell-cell contacts . They also show that one of the molecular reactants in this process are membrane glycoproteins with asparagine-linked oligosaccharides. Br J Dermatol, 1985 Jun, 112(6), 709 - 13 A dermatosis associated with bacterial overgrowth in jejunal diverticula; Fairris GM et al.; A patient is described with an unusual skin eruption associated with bacterial overgrowth in jejunal diverticula and malabsorption . The initial skin changes were frankly vasculitic with "target' lesions, whilst older lesions showed a psoriasiform scale and a tendency to central clearing . The illness was associated with raised levels of IgM and IgG containing circulating immune complexes and deposition of IgM and IgG in the dermis . It was suppressed by oral antibiotic therapy . There are similarities between the findings in this patient and those described in the intestinal bypass syndrome. Pathol Biol (Paris), 1985 Jun, 33(5 Pt 2), 533 - 7 {Aztreonam . Diffusion into bronchial mucus}; Morel C et al.; In a prospective study of antibiotics' diffusion into human bronchial mucus, we compared serum and mucus concentrations of aztreonam, a new beta lactam belonging to the monobactam group . Twenty patients were given aztreonam (1 g twice a day) for an acute purulent exacerbation of chronic bronchitis and divided into four groups according to the time of sampling (0.5, 1, 1.5 or 3 h) . Samples were taken on the first and third treatment days . Antibiotic concentrations were assayed using agar diffusion and HPLC . Aztreonam concentrations were low, similar to those achieved with other beta lactams . According to the time sampling, levels ranged from 0.27 to 1 mg/l and 0.4 to 1.15 mg/l on the first and third treatment days respectively . Corresponding serum levels were 90 mg/l and 30 mg/l, respectively 30 mn and 3 h after dose ingestion. Biochem Int, 1985 Jun, 10(6), 855 - 61 Ribosomes from a relC mutant strain of Escherichia coli show altered activity with bacterial release factor-1; Ward CD et al.; Ribosomes from a relC mutant of Escherichia coli, JF505, are altered in the large subunit protein L11 . This protein has abnormal mobility on gel electrophoresis . The ribosomes have a lowered specific activity for release factor-1 which is intermediate between that found for ribosomes containing normal L11 and that for L11 lacking ribosomes . JF505 ribosomes are as sensitive to inactivation of in vitro termination by thiostrepton as normal ribosomes when the antibiotic is added in dimethylsulphoxide but less sensitive when it is added in ethanol. Prostaglandins, 1985 Jun, 29(6), 961 - 80 Prevention of cecitis in hamsters by certain prostaglandins; Robert A et al.; Acute inflammation of the colon (cecitis) was produced in hamsters by daily subcutaneous administration of an antibiotic for 3 days . The following prostaglandins completely prevented the cecitis: 16,16-dimethyl-PGE2, 15(R)-15-methyl-PGE2, and 2-acetyl-2-decarboxy-15(S)-15-methyl-PGF2 alpha . PGF2 beta was less active . The synthesis of 2-acetyl-2-decarboxy-15(S)-methyl-PGF2 alpha is described . Castor oil also prevented the cecitis and peanut oil exerted partial protection . Since these oils contain linoleic acid, a precursor of PGE1, protection may have been due to endogenous formation of that prostaglandin . A partial block of the protective effect of castor oil by treatment with indomethacin supports such mechanism . The tissue level of endogenous prostaglandins seems to exert protection since administration of cyclooxygenase inhibitors, indomethacin and aspirin, markedly increased the incidence of cecitis . Magnesium sulfate given orally and sodium salicylate given subcutaneously reduced the incidence of cecitis only partially . The following agents were inactive: loperamide, an antidiarrheic agent; carbachol, a cholinergic and diarrheogenic agent, atropine, an anticholinergic agent; and acetazolamide, a carbonic anhydrase inhibitor . These results, show that certain prostaglandins, which have been shown earlier to be cytoprotective for the stomach and the small intestine, are cytoprotective for the large intestine as well. Am J Hematol, 1985 Jun, 19(2), 167 - 76 Treatment of patients with acute nonlymphocytic leukemia in relapse: a Leukemia Intergroup study; Goldberg J et al.; Forty patients with acute nonlymphocytic leukemia (ANLL) in first relapse were treated at eight member institutions of the Leukemia Intergroup with a 10-day continuous intravenous infusion of cytosine arabinoside and an anthracycline antibiotic administered on days 1, 2, and 3 . Twenty of the 40 patients achieved a complete response . Seven of the patients who did not enter remission were drug-resistant failures, while 13 patients failed to enter remission for reasons other than persistent leukemia . Pretreatment parameters such as age, presence of infection, platelet count, and liver function tests were important predictors of survival . The percent bone marrow cellularity, the percent circulating abnormal (leukemic) cells, and the height of the white blood cell count prior to treatment were helpful in distinguishing patients who would enter remission from those who would not enter remission because of persistent leukemia. J Pediatr, 1985 Jun, 106(6), 995 - 1000 Similar hematologic changes in children receiving trimethoprim-sulfamethoxazole or amoxicillin for otitis media; Feldman S et al.; We report the hematologic changes in 90 black children who were randomized to receive a 10-day course of either trimethoprim-sulfamethoxazole (TMP-SMZ) or amoxicillin as therapy for acute otitis media . Absolute neutrophil counts less than 1500/mm3 developed at least once during the 23-day evaluation in 28 (57%) of the 49 children given TMP-SMZ and in 22 (54%) of the 41 who received amoxicillin . Incidence of leukopenia, thrombocytopenia, and anemia was negligible in both groups . Pancytopenia did not occur in any child . Absolute neutrophil counts had increased to greater than 1500/mm3 by the end of the study period in all of the patients but six, whose recovery required an additional 1 to 63 days . Decreased neutrophil counts in antibiotic-treated subjects remained within the range of findings for healthy black children, suggesting that a count less than 1500/mm3 may be an inappropriate criterion for an adverse drug effect . Neither TMP-SMZ nor amoxicillin produced hematologic effects that would detract from their continued use in children with infections caused by antibiotic-susceptible organisms. South Med J, 1985 Jun, 78(6), 711 - 3 Trimethoprim-sulfamethoxazole, pseudomembranous colitis, and spinal cord injury; Sugarman B; Antibiotic-associated colitis (pseudomembranous colitis) developed in four patients with spinal cord injury and taking oral trimethoprim-sulfamethoxazole . One hundred forty-eight (59%) of 251 patients with spinal cord injury who were evaluated had received this drug . Two of the four patients with pseudomembranous colitis did not promptly respond to therapy, and all four suffered significant further immobilization because of the disease . Pseudomembranous colitis readily occurs in at least certain population groups receiving trimethoprim-sulfamethoxazole. J Oral Maxillofac Surg, 1985 Jun, 43(6), 436 - 9 A re-evaluation of the role of tracheostomy in Ludwig's angina; Allen D et al.; Ten cases of Ludwig's angina that required surgical decompression in addition to intravenous antibiotic therapy are reviewed . The vocal cords were visualized in all ten patients following deep inhalational anesthesia to relieve trismus . Only one case required tracheostomy, which has previously been recommended as the treatment of choice for airway management; the other nine were intubated under direct vision. Am J Physiol, 1985 Jun, 248(6 Pt 1), G626 - 32 Sequential disaccharidase loss in rat intestinal blind loops: impact of malnutrition; Sherman P et al.; We studied lactase, maltase, and sucrase activities in the mucosa of self-filling blind loops (SFBL) in adult rats at weekly intervals after SFBL formation in order to determine the sequence in which disaccharidase activities fall . The studies were carried out on nourished and malnourished rats and extended to a recovery period induced by antibiotics to determine the effects of malnutrition on the establishment and repair of disaccharidase deficiencies caused by bacterial overgrowth . Malnutrition was produced by feeding 50% of the intake of paired rats fed ad libitum . Disaccharidase activities were determined in SFBL from nourished and malnourished rats at 7-day intervals until pandisaccharidase deficiency was established and during a 2-wk recovery period induced by antibiotics . Maximal SFBL bacterial counts in both nourished and malnourished groups of rats and brush-border glycoprotein degradation ratios were established at 7 days . In nourished rats only lactase was deficient at 7 days; maltase and sucrase fell later and sequentially . In malnourished rats all three disaccharidases were reduced at 7 days . Disaccharidase activities in self-emptying blind loops (SEBL), used as operated controls, were not decreased 28 days after surgery . Malnutrition had no effect on disaccharidase activities in the SEBL, and malnutrition did not affect recovery rates with antibiotic therapy . We conclude that small intestinal bacterial overgrowth causes a staggered loss of disaccharidase activities beginning with the loss of lactase activity . In the presence of bacterial overgrowth, malnutrition accelerates the conversion of a mono- to a pan-disaccharidase deficiency. Recomb DNA Tech Bull, 1985 Jun, 8(2), 47 - 51 The effect of colonizing mice with laboratory and wild type strains of E . coli containing tumor virus genomes; Smith C Jr et al.; Conventional, antibiotic-compromised, and germ-free mice were either fed or subcutaneously inoculated with laboratory or wild type strains of E . coli containing monomeric or dimeric forms of polyoma (PY) virus DNA . Mice were bled at 3 and 6 weeks following administration of E . coli and their sera examined for the presence of PY hemagglutination inhibiting antibodies . None of the mice developed PY infection; despite colonization of the intestinal tract accompanied by prolonged excretion of high titers (10(9) colony-forming units/gram feces) of E . coli harboring potentially infectious PY virus DNA, no evidence of infection could be demonstrated. Mol Cell Biol, 1985 Jun, 5(6), 1379 - 84 H-2Ld antigen encoded by a recombinant retrovirus genome is expressed on the surface of infected cells; Weis JH et al.; A recombinant murine retrovirus was constructed which contains, within its genome, a truncated version of the gene encoding the murine H-2Ld major histocompatibility antigen . The H-2Ld gene, which was inserted 3' of the env splice acceptor site in the recombinant retrovirus MSV-neo, lacked the 5' promoter and TATA sequences and the 3' transcription termination and polyadenylate addition sites of the normal H-2Ld gene . Transfection of the MSV-neo/H-2Ld plasmid (pLTV-11) into Y-2 cells resulted in the production of the transmissible recombinant retrovirus LTV-11 . Cells infected with LTV-11 virus were resistant to the eucaryotic antibiotic G418 and expressed H-2Ld on the cell surface . These infected cells contained a viral RNA species which possessed both the H-2Ld and the neomycin resistance gene sequences but did not contain significant levels of the smaller H-2Ld-specific mRNA . The H-2Ld antigen expressed on the surface of infected cells functioned as a target for cytolytic T cells specific for the H-2Ld antigen. Cancer Lett, 1985 Jun, 27(2), 215 - 9 Adriamycin does not affect the repair of X-ray induced DNA single strand breaks; Cantoni O et al.; The ability of the antitumor antibiotic adriamycin (Ad) to inhibit the rejoining of DNA single strand breaks produced by X-rays was investigated in cultured cells . Chinese hamster ovary (CHO) cells were given 400 rad and were allowed to repair in the presence or absence of Ad for 60 min at 37 degrees C . The drug did not affect the ability of cells to repair DNA breaks and residual breaks found after the repair period were attributable to those induced by Ad alone. J Virol, 1985 Jun, 54(3), 682 - 9 Intracellular transport of herpes simplex virus gD occurs more rapidly in uninfected cells than in infected cells; Johnson DC et al.; A mouse L cell line which expresses the herpex simplex virus type 1 immediate-early polypeptides ICP4 and ICP47 was cotransfected with a cloned copy of the BglII L fragment of herpes simplex virus type 2, which includes the gene for gD, and the plasmid pSV2neo, which contains the aminoglycosyl 3'-phosphotransferase (agpt) gene conferring resistance to the antibiotic G418 . A G418-resistant transformed cell line was isolated which expressed herpes simplex virus type 2 gD at higher levels than were found in infected cells . The intracellular transport and processing of gD was compared in transformed and infected cells . In the transformed Z4/6 cells gD was rapidly processed and transported to the cell surface; in contrast, the processing and cell surface appearance of gD in infected parental Z4 cells occurred at a much slower rate, and gD accumulated in nuclear membrane to a greater extent . Thus, the movement of HSV-2 gD to the cell surface in infected cells is retarded as viral glycoproteins accumulate in the nuclear envelope, probably because they interact with other viral structural components. Endocrinology, 1985 Jun, 116(6), 2341 - 6 Tunicamycin and neuraminidase effects on luteinizing hormone (LH)-releasing hormone binding and LH release from rat pituitary cells in culture; Schvartz I et al.; We have studied the effects of tunicamycin (TM) and neuraminidase on the binding of 125I-labeled Buserelin, a GnRH agonist, and on GnRH-stimulated LH release in cultured rat pituitary cells . Treatment with TM, an antibiotic which inhibits protein glycosylation, abolished the development of elongated cell processes without any effect on cell viability . Concomitantly, TM caused a time- and dose-dependent inhibition of specific binding of Buserelin and of GnRH-stimulated LH release . The inhibition of binding was due to a decrease in the number of GnRH receptors without any significant effect on binding affinity . Protein synthesis was not affected under these experimental conditions, suggesting that the aglycosylated GnRH receptors are probably intracellularly accumulated and are not expressed on the cell surface . Treatment with neuraminidase inhibited only 50% of GnRH agonist binding and did not affect GnRH-stimulated LH release . These results indicate that the oligosaccharide portion is essential for the functional properties of the GnRH receptor. J Biomol Struct Dyn, 1985 Jun, 2(6), 1085 - 95 Netropsin specifically recognizes one of the two conformationally equivalent strands of poly(dA).poly(dT) . One dimensional NMR study at 500 MHz involving NOE transfer between netropsin and DNA protons; Sarma MH et al.; Recent observations that the heteronomous structural model for poly(dA).poly(dT) is not found in solution and that in this DNA, the two strands are conformationally equivalent (J . Biomole . Str . Dyns . 2, 1057 (1985}, has added a new dimension to the structural dynamics of DNA-netropsin complex . Does the antibiotic somehow distinguish between the two strands and specifically interact with only one of the conformationally equivalent strands? Model-building studies suggest that netropsin can either bind to the dA-strand in the minor groove such that H-bonds are formed between the imino protons N4-H, N6-H, N8-H of netropsin and N3 atoms of A or can bind to the dT-strand in the minor groove and form H-bonds between the imino-protons N4-H, N6-H, N8-H of netropsin and O2 atoms of T . If netropsin binds to the dA-strand, AH2 atoms of poly(dA).poly(dT) would be in closer proximity to the imino protons N4-H, N6-H, N8-H and pyrrole ring protons C5-H, C11-H of netropsin than they would be, if netropsin binds to the dT-strand . In order to distinguish these possibilities experiments were conducted which involved NOE energy transfer between netropsin and DNA protons in the drug-DNA complex . Difference NOE spectra of netropsin-poly(dA).poly(dT) complex in which AH2 was irradiated indicate that dominant NOEs were observed at the imino and pyrrole ring protons of netropsin . When the netropsin pyrrole ring protons were irradiated, the magnetization transfer was at AH2 of DNA . These observations suggest that netropsin binds to the dA-strand of poly(dA).poly(dT) even though dA/dT strands are conformationally equivalent. Biochim Biophys Acta, 1985 May 29, 840(1), 91 - 8 Physicochemical studies of the iron(III)-carminomycin complex and evidence of the lack of stimulated superoxide production by NADH dehydrogenase; Fiallo MM et al.; Fe(III) complex of an antitumoral antibiotic carminomycin has been studied . Using potentiometric and spectroscopic measurements we have shown that carminomycin forms with Fe(III) a well-defined species in which three molecules of drug are chelated to one Fe(III) ion . This occurs with the release of one proton per molecule of drug . Magnetic susceptibility measurements suggest that six oxygen atoms are bound to iron . The stability constant is 3 X 10(34) . The in vitro inhibition of P 388 leukemia cell growth by this complex compares with that of the free drug . This complex, unlike the free drug, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase. J Mol Biol, 1985 May 5, 183(1), 13 - 29 Novobiocin blocks the Drosophila heat shock response; Han S et al.; In the studies reported here we show that the antibiotic novobiocin, an in vitro inhibitor of topoisomerase II, blocks the Drosophila heat shock response . If novobiocin is added prior to induction, there is no detectable expression of the Drosophila heat shock genes . Moreover, analysis of the chromatin organization of the 87A7 heat shock locus indicates that the antibiotic prevents the structural alterations which normally accompany heat induction . When novobiocin is added after induction, transcription appears to be rapidly turned off, and the chromatin organization of the 87A7 locus is "fixed" in an "active" configuration . Novobiocin also prevents the re-establishment of the pre-induced 87A7 chromatin organization which occurs during recovery from heat shock . We have also presented data suggesting that this antibiotic blocks transcription at 25 degrees C . These findings raise the possibility that topoisomerase II may be required in eukaryotes for both gene activation and deactivation. Br Med J (Clin Res Ed), 1985 May 4, 290(6478), 1321 - 2 Has treatment for childhood gastroenteritis changed? Kumar GA, Little TM. Because so many children with gastroenteritis in our area were being treated with drugs, which are potentially harmful, we assessed the extent of treatment before admission to hospital of 288 children . Sixty four had been treated: 45 with antibiotic, antidiarrhoeal, or antiemetic drugs and 34 had been given glucose-electrolyte solution, 15 of those had also been given drugs; 119 had had no treatment . Since 1979 there has been a decrease in the use of drugs for gastroenteritis, but glucose-electrolyte mixtures are still underused. Ann Plast Surg, 1985 May, 14(5), 454 - 7 Meat grinder injuries to the upper extremity; Brandner M et al.; Three cases of hand injury caused by meat grinders are presented . All 3 injuries involved the dominant hand and resulted in varying degrees of deformity . Two of the 3 patients arrived in the emergency room with the injured hand still firmly wedged in the meat grinder . Although these injuries continue to prove very mutilating, maximum restoration of the injured hand can be accomplished by careful extrication, followed by preservation and reconstruction of all viable tissues . Perioperative antibiotics and wound irrigation with antibiotic solution are recommended . Microsurgical technique can be of value in treating selected patients. Eur J Cell Biol, 1985 May, 37, 63 - 9 Distribution of intramembranous particles and filipin-sterol complexes in the cell membranes of Toxoplasma gondii; Cintra WM et al.; Toxoplasma gondii possesses a plasma membrane covering the whole cell and, below it, two closely apposed unit membranes interrupted at the anterior and posterior tips of the parasite and at the micropore . Density differences of intramembranous particles (IMP) were observed among the various membranes . The polyene antibiotic filipin was used for the detection of sterols in freeze-fractured membranes of the parasite . Protuberances with a mean diameter of 38 nm, indicative of the formation of filipin-sterol complexes, were seen in the P and E faces of the plasma membrane . The density of filipin-sterol complexes on the P and E faces of the plasma membrane was 130 +/- 45 and 101 +/- 50 protuberances/micron2, respectively . Few or no protuberances were seen on both fracture faces of the intermediate and inner membranes . The results obtained are discussed and compared with those obtained in other parasites enclosed with a complex membrane system. Antibiot Med Biotekhnol, 1985 May, 30(5), 352 - 5 {Pharmacokinetics of sisomicin during hemosorption and hemodialysis}; Firsov AA et al.; The effect of hemosorption and hemodialysis on the pharmacokinetics of sisomicin was studied in 17 patients with acute and chronic renal insufficiency . The value of the antibiotic extraction coefficient in hemosorption was almost 2 times higher than that in hemodialysis . In patients on hemosorption, extracorporeal elimination of the antibiotic was of the saturation nature . It was characterized by systematic diminishing of the extraction coefficient, while in patients on hemodialysis, it did not depend on the time (the value of the extraction coefficient was constant) . In this connection it is recommended that the rate of diminishing of the extraction coefficient in hemosorption be estimated . Since sisomicin is rapidly absorbed by the column it is not advisable to administer sisomicin to patients before hemosorption. Antibiot Med Biotekhnol, 1985 May, 30(5), 344 - 8 {Effect of levorin and its combination with a modifying factor on the fatty acid composition of Crithidia oncopelti lipids}; Chuenkova MV et al.; It was shown by us earlier that the sensitivity of Crithidia oncopelti to levorin, a polyene antibiotic, increased in the presence of sodium acetate as a modifying factor . A simultaneous change in the ratio of C . oncopelti structural lipids was also observed . The present paper deals with investigation of the effect of levorin and its combination with the modifying factor on the fatty acid composition of C . oncopelti lipids . The study showed that addition of sodium acetate in a concentration of 40 mg/ml to the medium for cultivation of C . oncopelti resulted in an increase in the total level of fatty acid unsaturation at the expense of a significant increase in the content of linoleic acid and polyunsaturated acids . The content of monoene fatty acids simultaneously decreased . In a concentration of 1 microgram/ml levorin had no effect on the growth of C . oncopelti and did not practically change the relative content of its fatty acids . Combined addition of levorin (1 microgram/ml) and sodium acetate (40 mg/ml) to the medium resulted in inhibition of the culture growth by 60-80 per cent and a marked increase in the total content of saturated acids with a decrease in the level of monounsaturated and polyunsaturated acids . The trypanostatic concentration of levorin (10 micrograms/ml) had the same effect and also lowered the total level of unsaturated fatty acids of C . oncopelti.(ABSTRACT TRUNCATED AT 250 WORDS) Antibiot Med Biotekhnol, 1985 May, 30(5), 331 - 4 {Characteristics of the process of regulated biosynthesis of oxytetracycline}; Bobyleva RI et al.; Investigation of the process of oxytetracycline biosynthesis in a model medium showed that addition of maltose during the phase of antibiotic biosynthesis resulted in an increase in the rate of the culture growth, prolongation of the antibiotic production phase and increased productivity of the mycelium . The productive mycelium was characterized by a higher content of total nitrogen and phosphorus. Int J Biomed Comput, 1985 May, 16(3-4), 231 - 43 Empirical and mathematical models on the relationship between patient age and nosocomial infection; Goonatilake PC; This paper proposes two models, one a purely empirical one and the other a mathematical one, which depict the relationship between patient age and nosocomial infection rate . The empirical model is based on the two age-specific phenomena, the acquisition of resistance to infection with age mainly in the early years of life and the deterioration of existing resistance mechanisms with ageing predominantly in the later years of life . The net effect of these two factors is shown to approximate into a quadratic relationship between age and nosocomial infection rate, like the type demonstrated in earlier experimental studies . The second mathematical model is derived from studies on cancer research and here the relationship between age and nosocomial infection rate for patients in the age group 30-70 years is represented by a log linear model . The model was tested against experimental data derived from large surveys on nosocomial infection and the resulting correlation coefficient was 0.98 . The model was an extremely good fit when tested against postoperative wound infection rates as well as nasal carriage rate of antibiotic resistant Staph . aureus . Furthermore, when patients in the survey were subdivided into groups of male patients and female patients and into two groups based on the type of operative wound, the model was still found to be a very good fit to the experimental data . This confirmed the validity of the model even in the presence of other patient-related parameters . Finally, the model was tested against the results of a totally different experimental study conducted elsewhere and the resulting correlation coefficient was 0.999, which confirmed the validity of the model in a universal context. Clin Nephrol, 1985 May, 23(5), 241 - 4 Oral treatment of peritonitis complicating continuous ambulatory peritoneal dialysis; Searle M et al.; The efficacy of oral treatment with cephradine in peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD) was compared with that of intraperitoneal cefuroxime over one year . There were 29 episodes of peritonitis in each group and a primary cure was achieved in 66% of the patients treated with cephradine compared with 55% of the patients treated with cefuroxime, suggesting that oral cephradine is as effective as a treatment with intraperitoneal cefuroxime . Nineteen of the 29 episodes in each treatment group were considered suitable for out-patient management and there was no difference in the success rate of either antibiotic regimen . The results suggest that out-patient treatment with oral cephradine is an efficient way of treating CAPD peritonitis. Biull Eksp Biol Med, 1985 May, 99(5), 540 - 2 {Blocking effect of cycloheximide on decreased mitochondrial resistance due to thyroid hormone action}; Marzoev AI et al.; Administration of cycloheximide (20-25 micrograms/kg bw twice, interval 24 h) to hyperthyroid rats (300 micrograms/T4/100 g bw i . p . 48 h before sacrifice) inhibited the decrease in mitochondrial resistance to Ca2+ characteristic of hyperthyroidism . It was established in particular that calcium capacitance of the mitochondria and the time of the maintenance of transmembrane potential of these organelles under calcium loading were increased in the mitochondria of hyperthyroid animals given cycloheximide as compared with analogous parameters of the organelles of intact hyperthyroid rats . Moreover, the fluorescence intensity of NADPH in the mitochondria of the first group of animals was 37% greater and the rate of oxidation of these nucleotides several times lower than in the organelles of the second group animals . It is assumed that the described effects of cycloheximide on the mitochondria are linked with the inhibitory effect of the antibiotic on endogenous activity of mitochondrial phospholipase A2. Ann Rheum Dis, 1985 May, 44(5), 336 - 40 Rheumatoid bursitis extending into the clavicle and to the skin surface; Bassett LW et al.; A woman with rheumatoid arthritis developed persistent sterile drainage from a cutaneous fistula after biopsy of an inflamed supraclavicular mass . Radiographs showed several cavities in the underlying clavicle . Inability to culture a pathogen and failure of the fistula to heal despite empirical courses of antibiotic therapy led to surgical intervention . The final diagnosis, based on careful histological analysis by special staining techniques, was rheumatoid bursitis extending into the clavicle and to the skin surface. Am J Hosp Pharm, 1985 May, 42(5), 1083 - 6 Time and cost comparison of four methods of filling drug manufacturers' piggyback bottles; Anderson ER Jr et al.; The times and costs required for four methods of reconstituting i.v . antibiotic doses in drug manufacturers' piggyback bottles (DMPBs) were compared . Instafil filling devices were used with (1) a pressure cuff (Instafil Instafusor) for the diluent bag, (2) a peristaltic pump (Wheaton Unispense), and (3) a vacuum line . The fourth method used a vacuum line and a control handle (Vacu-fil, American McGaw) . Batches of 20 bottles filled to 50 mL and 20 bottles filled to 100 mL (three trials each) and 60 bottles filled to 100 mL (two trials) were prepared by each of the four methods . The Instafil with vacuum line was significantly faster than the other methods used to fill batches of 20 DMPBs with 50 mL and 100 mL of diluent . It was also significantly faster than the Vacu-fil and the Instafil with the cuff for filling batches of 60 DMPBs with 100 mL of diluent . For batches of 60 DMPBs, the fill times for the Instafil with vacuum line and the Instafil with the peristaltic pump were not significantly different . For the batches of 20 50-mL DMPBs, overall cost per dose for the Instafil with vacuum line was $0.36, followed by Instafil with the pump ($0.37), Instafil with cuff ($0.38), and Vacu-fil ($0.54) . Other batch sizes and fill volumes ranked similarly . Of the methods tested, the Instafil device with a vacuum line was the most efficient and cost-effective for preparing batches of 20 to 60 i.v . antibiotic doses in manufacturers' piggyback bottles. J Hand Surg {Am}, 1985 May, 10(3), 364 - 70 Open dorsal dislocations of the proximal interphalangeal joint; Stern PJ et al.; Eighteen open dorsal dislocations of the proximal interphalangeal joint were treated in 17 patients over a 12-year period . The severity of this injury may be underestimated . Complications included synovitis, stiffness, septic arthritis, and loss of the digit . Factors associated with a poor prognosis included a concomitant injury to the hand, a fracture from the base of the middle phalanx, and treatment in the emergency room . For optimum results, we recommend antibiotic therapy, thorough debridement in the operating room, reattachment of the palmar plate and repair of the collateral ligaments if necessary, and temporary joint immobilization (3 weeks) followed by an aggressive range of motion program. Invest Ophthalmol Vis Sci, 1985 May, 26(5), 719 - 25 Daunomycin in the treatment of experimental proliferative vitreoretinopathy . Effective doses in vitro and in vivo; Wiedemann P et al.; In previous studies the authors have shown that daunomycin, an anthracycline antibiotic, when injected into the vitreous effectively controls experimental proliferative vitreoretinopathy . Here we show that by administering daunomycin intravitreally it is possible to achieve in vivo concentrations that prevent fibroblast proliferation in vitro . The authors have also determined that the half-life of daunomycin in the vitreous is 131 min, indicating that a critical concentration is maintained in the eye for longer than 4 hr after a single injection . Using 3H-daunomycin, the authors have found that the drug is eliminated across the retina; no significant binding of the drug to vitreous components occurs . These studies demonstrate that it is possible to define the kinetics of drugs injected into the vitreous; and a knowledge of the distribution of any drug in ocular tissues is necessary to effectively determine whether such drug is of therapeutic value. Dis Colon Rectum, 1985 May, 28(5), 347 - 52 Barium peritonitis . Report of a case and review of the literature; Yamamura M et al.; A case of generalized peritonitis, secondary to a perforation of the rectosigmoid colon during barium-enema roentgenography, is presented . The patient required immediate surgical intervention with the prime importance of the treatment being removal of as much of the contaminating materials as possible . This was done successfully with irrigation and wiping, using urokinase solution . Peritoneal lavage with urokinase solution was also carried out in the early postoperative period . Fluid replacement with careful monitoring of fluid and electrolyte balance is essential before, during, and after the surgical procedure . Adequate antibiotic therapy and careful respiratory and nutritional support are also important. Cell, 1985 May, 41(1), 201 - 9 Pleiotropic mutants of NIH 3T3 cells with altered regulation in the expression of both type I collagen and fibronectin; Setoyama C et al.; Transformation of NIH 3T3 fibroblasts by v-mos causes a decrease in the levels of type I collagen RNA . In NIH 3T3 cells that have been made resistant to G418 by transfection with a plasmid in which the mouse alpha 2(I) collagen promoter is linked to the neo gene, subsequent v-mos transformation causes a loss of G418 resistance . After mutagenesis of these v-mos-transformed cells, G418-resistant colonies were selected . Two of these G418-resistant mutants showed an increased expression of the neo gene and of the endogenous type I collagen and fibronectin genes, without changes in their levels of v-mos RNA or in their ability to induce tumors . The mutations might alter cellular trans-acting factors that either directly or indirectly control the expression of the type I collagen and fibronectin genes in transformed cells. Am J Obstet Gynecol, 1985 May 1, 152(1), 89 - 90 Aminoglycoside dosing in obese puerperal women; Gibbs RS et al.; We compared serum aminoglycoside levels in two groups of obese puerperal women being treated for endometritis . In these obese puerperal women (weights as much as 100 kg), the aminoglycoside dose did not have to be adjusted for excess weight initially, but it seems that determination of antibiotic levels should be performed in view of the large doses. Am J Cardiol, 1985 May 1, 55(11), 1293 - 7 Selective absorption of ultraviolet laser energy by human atherosclerotic plaque treated with tetracycline; Murphy-Chutorian D et al.; Tetracycline is an antibiotic that absorbs ultraviolet light at 355 nm and preferentially binds to atherosclerotic plaque both in vitro and in vivo . Tetracycline-treated human cadaveric aorta was compared with untreated aorta using several techniques: absorptive spectrophotometry, which demonstrated a distinct absorptive peak at 355 nm in tetracycline-treated plaque that was absent in treated normal vessel; ultraviolet microscopy, which showed that treated atheroma acquired the characteristic fluorescence of tetracycline under ultraviolet light; and tissue uptake of radiolabeled tetracycline, which showed 4-fold greater uptake by atheroma than by normal vessel . In addition, intravenous tetracycline administered to patients undergoing vascular surgery demonstrated characteristic fluorescence in surgically excised diseased arteries . Because of tetracycline's unique properties, we exposed tetracycline-treated and untreated aorta to ultraviolet laser radiation at a wavelength of 355 nm . We found enhanced ablation of tetracycline-treated atheroma compared with untreated atheroma . The plaque ablation caused by ultraviolet laser radiation was twice as extensive in tetracycline-treated vs nontreated plaque (2.2 +/- 0.25 mm vs 1.3 +/- 0.55 mm, p less than 0.017) . This study demonstrates the potential of tetracycline plaque enhancement for the selective destruction of atheroma by ultraviolet laser radiation. Am J Dis Child, 1985 May, 139(5), 464 - 6 Isolated deafness following recovery from neurologic injury and adult respiratory distress syndrome . A sequela of intercurrent aminoglycoside and diuretic use; Lynn AM et al.; We report two children who survived neurologic injury (near-drowning and Reye's syndrome) and adult respiratory distress syndrome and who required prolonged ventilatory support . Follow-up examination in both children showed steady neurologic recovery, but five months following discharge from their acute illness, profound hearing loss was diagnosed in both children . A review of the literature is reported and the hypothesis that combined aminoglycoside antibiotic and loop diuretic therapy caused the hearing loss is presented . Recommendation is made for audiologic assessment within six months of recovery from critical illness of pediatric patients in whom therapy has included loop diuretic and aminoglycoside antibiotic therapy. Jpn J Antibiot, 1985 May, 38(5), 1272 - 8 {Clinical trial and basic study on the tissue transfer of cefminox}; Kosakai H et al.; Cefminox (CMNX, MT-141) was studied both fundamentally and clinically with following results: In the treatment of 3 cases of Bartholin's abscess, 2 cases of pyometra, and 1 case each of bartholinitis, inflammation of the pelvic dead space, retroperitoneal abscess and pelvic peritonitis, CMNX was administered at a dosage of 1 g . The global clinical results were rated as good in 9 cases . From these findings it is considered that CMNX is promising as an antibiotic with extremely high efficacy for infections of the field of obstetrics and gynecology . Furthermore, since in none of our cases side effects or laboratory abnormalities were observed, CMNX is considered to be a drug with high efficacy and safety . In 5 cases received 1 g of CMNX intravenously, concentrations of the drug in the serum and tissues of internal genital organs were determined . CMNX was maintained at concentrations higher than 20 micrograms/ml for the serum and 10 micrograms/g for each tissue studied . In the pelvic dead space exudate 10 to 20 micrograms/ml of the drug was still detected even at 8 hours after the administration . These results obtained by our fundamental study support the efficacy of CMNX demonstrated in the clinical part of our study. Jpn J Antibiot, 1985 May, 38(5), 1268 - 71 {Basic and clinical studies on cefminox in the field of obstetrics and gynecology}; Horii T et al.; Basic and clinical studies were carried out on cefminox (CMNX, MT-141), a new cephem antibiotic . Results obtained were as follows . Following each 1 g of intravenous drip infusion and intravenous injection, transfer of CMNX to the internal genital organs was good . Transfer of CMNX into exudate of the pelvic dead space was also good and showed high concentration . CMNX was given to 2 cases . Clinical efficacy was good in 1 case, and could not be evaluated in 1 case . No side effects were observed in both cases . The above results show that CMNX is an effective agent. Jpn J Antibiot, 1985 May, 38(5), 1260 - 7 {Basic and clinical studies on cefminox in the field of obstetrics and gynecology}; Yamamoto T et al.; Fundamental and clinical studies on cefminox (CMNX, MT-141), a new cephamycin antibiotic, were performed and the following results were obtained . Concentration of CMNX was examined in serum, internal genital organs and retroperitoneal fluid after a single intravenous administration of 1.0 g dose . The venous serum level of CMNX was 62.8 +/- 7.02 microgram/ml (Mean +/- S.D.) at 30 minutes after the administration . The sufficient transfer of CMNX to internal genital organs and retroperitoneal fluid was demonstrated . In clinical trial, CMNX was given to 10 cases with obstetrical and gynecological infections . The efficacy was evaluated as excellent in 1 case, good in 8 cases and poor in 1 case . No side effects were observed in any of the cases treated with CMNX. Jpn J Antibiot, 1985 May, 38(5), 1244 - 53 {Basic and clinical studies on cefminox in the field of obstetrics and gynecology}; Itoh K et al.; In order to determine transference of cefminox (CMNX, MT-141) into the female genital organ tissues, the drug concentration in the pelvic dead space exudate was measured in cases undergone radical hysterectomy due to uterocervical cancer . For analysis of data the three-compartment model was used . When CMNX was given at a dose of 1 g as an intravenous drip infusion taking 1 hour, the serum concentration of the cubital vein reached its peak of 89.53 microgram/ml at 1 hour after start of administration . In the pelvic dead space exudate the peak concentration of 39.84 microgram/ml was reached at 2.55 hours after administration and a concentration higher than 7 micrograms/ml was still detected even at 12 hours . The area under the curve (AUC) for CMNX concentration in the pelvic dead space exudate was 295.63 microgram X hr/ml . These results suggest that CMNX achieves high concentration in the pelvic dead space exudate and that it is an antibiotic with clinical utility . CMNX was used in the treatment of 6 cases of obstetrical and gynecological infections . The clinical results were excellent in 1 case, good in 2 cases and poor in 2 cases . In the remaining 1 case the results was unknown. Jpn J Antibiot, 1985 May, 38(5), 1225 - 35 {Fundamental and clinical studies on cefminox in the field of obstetrics and gynecology}; Fukuda T et al.; Cefminox (CMNX, MT-141), a new cephamycin antibiotic, was studied both fundamentally and clinically with following results . In 33 cases undergone total hysterectomy and adnexectomy, 1 g of CMNX was administered intravenously by the drip infusion route over 1 hour and changes in drug concentration in the venous blood and uterine arterial blood as well as in various uterine tissues including endometrium, myometrium, cervix uteri, portio vaginalis, oviduct and ovary were studied . In addition, in 3 cases also received 1 g of CMNX over 1 hour by the drip infusion route, changes in the concentration of CMNX in the pelvic dead space exudate were investigated . In each tissue studied, the drug concentration higher than 40 micrograms/g was attained at 20 minutes after completion of drip infusion, showing good transfer of CMNX . In the pelvic dead space exudate, the peak concentration of 24.7 micrograms/ml appeared at 4 hours after completion of drip infusion and at 12 hours still a concentration of 4.5 micrograms/ml was maintained . In the treatment of 15 cases of obstetrical and gynecological infections, CMNX was used . In all of the cases treated, clinical results better than good were obtained, with excellent results in 2 cases and good results in 13 cases . In none of the cases side effects or laboratory abnormalities were observed . From these results CMNX is considered to be a useful drug for the treatment of various infections in the field of obstetrics and gynecology. Jpn J Antibiot, 1985 May, 38(5), 1208 - 12 {Use of cefminox in infections in the field of obstetrics and gynecology}; Okamura K et al.; A total of 15 cases of obstetrical and gynecological infections was treated with cefminox (CMNX, MT-141), a new cephamycin antibiotic, with following results . The subjects consisted of 3 cases of salpingitis, 2 cases of parametritis, 5 cases of endometritis, and 1 case each of puerperal fever, inflammation of the pelvic dead space, Bartholin's pyocele, vulvar abscess and suppurative mastitis . In 2 cases of endometritis, pelveoperitonitis and adnexitis were complicated, respectively . As a rule, CMNX was administered intravenously at a dosage of 1 g each twice a day by drip infusion route . The clinical results were rated as excellent in 8 cases, good in 6 cases and poor in 1 case, with an efficacy rate of 93.3% . No subjective or objective side effects were seen nor any abnormal laboratory test results were found. Jpn J Antibiot, 1985 May, 38(5), 1203 - 7 {Clinical studies on cefminox in the field of obstetrics and gynecology}; Chimura T et al.; Clinical and laboratory studies on cefminox (CMNX, MT-141), a new injectable cephamycin antibiotic, were made in the field of obstetrics and gynecology, and following results were obtained . In the clinical trial, 12 cases were treated with CMNX given by intravenous drip infusion . The results were excellent in 2 cases, good in 8 cases and poor in 2 cases . The effectiveness rate was 83.3% . No side effect was recognized . No significant changes of laboratory findings were noticed. Proc Natl Acad Sci U S A, 1985 May, 82(10), 3212 - 6 A second tRNA binding site on elongation factor Tu is induced while the factor is bound to the ribosome; Van Noort JM et al.; Previously, we reported that the antibiotic kirromycin induces two tRNA-binding sites on the elongation factor Tu . The classical binding site (site I) binds aminoacyl-tRNA and, with much less affinity, deacylated tRNA . The kirromycin-induced site II binds aminoacyl-tRNA, peptidyl-tRNA, and deacylated tRNA with comparable affinities . Accordingly, 3'-oxidized tRNA can be cross-linked in the presence of the antibiotic to two specific sites of EF-Tu: Lys-237 and Lys-208 . Here, we report that 3'-oxidized tRNAPhe, bound to a ribosome-poly(U) complex, can also be cross-linked to either one of these two sites . When located in the ribosomal peptidyl site, it cross-links exclusively to Lys-208; when located in the ribosomal aminoacyl site, it cross-links exclusively to Lys-237, irrespective of the presence of kirromycin . Since no cross-linking could be detected in the absence of ribosomes and kirromycin, we conclude that the tRNA-binding site II is induced upon interaction of aminoacyl-tRNA-EF-Tu-GTP with the ribosome-mRNA complex . The results indicate that, on the ribosome, EF-Tu interacts with peptidyl-site-bound peptidyl-tRNA through tRNA-binding site II and with aminoacyl-site-bound aminoacyl-tRNA through tRNA-binding site I. J Am Coll Cardiol, 1985 May, 5(5 Suppl A), 43A - 50A Pharmacokinetics, bioavailability and serum levels of cardiac glycosides; Smith TW; Digoxin, the cardiac glycoside most frequently used in clinical practice in the United States, can be given orally or intravenously and has an excretory half-life of 36 to 48 hours in patients with serum creatinine and blood urea nitrogen values in the normal range . Since the drug is excreted predominantly by the kidney, the half-life is prolonged progressively with diminishing renal function, reaching about 5 days on average in patients who are essentially anephric . Serum protein binding of digoxin is only about 20%, and differs markedly in this regard from that of digitoxin, which is 97% bound by serum albumin at usual therapeutic levels . Digitoxin is nearly completely absorbed from the normal gastrointestinal tract and has a half-life averaging 5 to 6 days in patients receiving usual doses irrespective of renal function . The bioavailability of digoxin is appreciably less than that of digitoxin, averaging about two-thirds to three-fourths of the equivalent dose given intravenously in the case of currently available tablet formulations . Recent studies have shown that gut flora of about 10% of patients reduce digoxin to a less bioactive dihydro derivative . This process is sensitive to antibiotic administration, creating the potential for important interactions among drugs . Serum or plasma concentrations of digitalis glycosides can be measured by radioimmunoassay methods that are now widely available, but knowledge of serum levels does not substitute for a sound working knowledge of the clinical pharmacology of the preparation used and careful patient follow-up. Gynecol Oncol, 1985 May, 21(1), 54 - 64 Chemical induction of ovarian tumors in rats; Tunca JC et al.; The production and pathogenesis of ovarian cancer was investigated in noninbred albino weanling female rats by surgical fixation into the left ovaries of sutures chemically impregnated with the chemical carcinogens formic acid 2-{4-(5-nitro-2-furyl)-2-thiazolyl}hydrazide (FNT), a nitrofuran antibiotic; N-methyl-N'-nitrosourea (MNU), a direct-acting alkylating agent; or 7,12-dimethylbenz{a}anthracene (DMBA) . Rats living more than 30 days following surgery were subjected to complete necropsy of external, thoracic, and abdominal tissues when they died or were killed at 407 days, the study termination . Mean survival of rats in treated and control groups was comparable . All carcinogen-treated rats exposed to FNT, MNU, or DMBA developed one or more ovarian, uterine, or mammary neoplasms with a total of 31 tumors in 22 rats as compared with no tumors in 5 control rats . All carcinogen-treated rats (22) developed ovarian adenomas (18) or adenocarcinomas (4); 3 developed uterine fibroadenomas (1) or squamous cell carcinomas (2); and 6 developed mammary adenocarcinomas . No neoplasms were present in the right ovaries of carcinogen-treated rats . These data suggest that direct application of carcinogens to ovarian tissue is a satisfactory way to develop ovarian adenoma and adenocarcinoma. Jpn J Antibiot, 1985 May, 38(5), 1389 - 419 {Clinical evaluation of the TMS-19-Q.GC tablet in odontogenic infections . A comparative double-blind study with josamycin}; Sasaki J et al.; Clinical efficacy and safety of TMS-19-Q.GC tablet (TMS), a new macrolide antibiotic preparation, were compared with those of josamycin (JM) in the treatment of acute odontogenic infection under multicentered double-blind controlled study at the daily dosage of 600 mg of TMS or 1,200 mg of JM . The results obtained were as follows: The patients entered into the study were 265 cases and 112 in TMS group and 111 in JM group were adopted to evaluate for the efficacy . The evaluation was made by 2 ways i.e . changes in total clinical scores of the symptom and the doctors assessment . Efficacy rating of TMS and JM were 81.3 and 82.0% judged by the score and 73.2 and 77.5% judged by doctors in charge respectively . In the cases with 15 to 20 of total scores at the initial visit, considered to be suitable for the evaluation of antibiotics, the efficacy rating of both drugs were 86.7% in TMS and 84.6% in JM . Organisms were isolated from 34 cases in TMS and 40 in JM and the clinical effectiveness in those cases were almost the same . Slight adverse reactions were observed in 6 cases (4.6%) of TMS group and 1 (0.8%) of JM . In 3 cases (4 incidences) of TMS group and 1 of JM slightly abnormal laboratory findings were found . On the statistical analysis of the data regarding efficacy, safety and usefulness, both drugs had no significant difference . From these results, TMS was considered as effective as JM in the treatment of acute odontogenic infection at a daily half doses of JM. J Urol, 1985 May, 133(5), 799 - 802 The use of ultrasound for evaluating subacute unilateral scrotal swelling; Pintauro WL et al.; In 15 patients with subacute (longer than 8 hours) unilateral scrotal swelling in whom the etiology was in doubt scrotal ultrasound was used to determine whether the pathological condition was intratesticular and/or extratesticular . Surgical exploration confirmed intratesticular or intratesticular and extratesticular findings in 9 patients: 8 had torsion of the spermatic cord (including a testis rupture in 1 and epididymal ruptures in 2) and 1 had a mixed germ cell carcinoma . Of the 6 patients with extratesticular findings 3 had clinical epididymitis that resolved on antibiotic therapy and 2 had what appeared to be paratesticular hematomas with normal testes presumed to be secondary to minor trauma . The condition resolved with conservative therapy in the latter 2 patients . The remaining patient required surgical drainage because of the size and an epididymal rupture suspected by the ultrasound examination . Scrotal ultrasound is a quick, noninvasive, easily applied, accurate method to diagnose scrotal pathological conditions and should be used whenever the etiology of scrotal swelling is in doubt. J Neurosurg, 1985 May, 62(5), 694 - 7 Results of trimethoprim-sulfamethoxazole prophylaxis in ventriculostomy and shunting procedures . A double-blind randomized trial; Blomstedt GC; The author reports the results of a study to assess the effectiveness of a trimethoprim-sulfamethoxazole combination as prophylaxis in ventriculostomy or shunting operations . Between 1980 and 1983, 122 patients undergoing shunting procedures were randomly assigned to receive trimethoprim-sulfamethoxazole (Group 1, 62 cases) or a placebo (Group 2, 60 cases) . The same regimen was followed at each operation, and the patients were followed for a minimum of 6 months . There was a higher infection rate in the placebo group (14 of 60 patients compared with 4 of 62 patients in the antibiotic group, p less than 0.01) . The antibiotic protected against early infections (nine of the 60 patients in Group 2 against none of the patients in Group 1), but not against late infections (four of the 62 in Group 1 compared with five of the 60 in Group 2) . During the same period, 52 patients undergoing ventriculostomy only were also randomly assigned to receive trimethoprim-sulfamethoxazole (Group 3) or placebo (Group 4) . There were no differences in the infection rates between these groups (one of 25 in Group 3 as against one of 27 in Group 4). J Gen Microbiol, 1985 May, 131 ( Pt 5), 1181 - 91 Genetic analysis in Streptomyces chrysomallus; Keller U et al.; A circular linkage map was developed for Streptomyces chrysomallus, a producer of actinomycin C . The map order of various marker loci was deduced from matings and to a minor extent from protoplast fusions . The map strongly resembles that of Streptomyces coelicolor A3(2) . The recombination frequencies were low and highly variable (from 10(-9) to 5 X 10(-6} . Plasmid pIJ303 expressed its thiostrepton resistance gene in S . chrysomallus but did not promote chromosomal transfer or induce the Ltz+ phenotype . The data provide a background of genetics for investigations of antibiotic synthesis in this strain. Mol Biol (Mosk), 1985 May-Jun, 19(3), 610 - 6 {Lambda plasmidophages and their properties}; Mel'nikov AA et al.; Plasmidphage lambda NM::pBR322 has been constructed in vitro and characterized . Under normal conditions the hybrid DNA molecule undergoes a lytic cycle of phage development, whereas in the presence of antibiotic lambda DNA replicates in the cell extrachromosomally as a plasmid . Properties of plasmidphage lambda NM::pBR322 have been compared with the earlier constructed lambda gt::pMB9 . It has been demonstrated that plasmid pMB9 in vivo can be precisely excised from the lambda gt::pMB9. Mol Cell Biochem, 1985 May, 67(1), 39 - 46 Inhibition of the formation of lipid-linked intermediates in normal and transformed cells by a purified tunicamycin homologue; Eren R et al.; The effects of a purified homologue of tunicamycin (B2-tunicamycin) on the biosynthesis of lipid-linked intermediates participating in protein glycosylation in normal embryonic fibroblasts, 3T3 and virally transformed (simian virus 40 and polyoma virus) mouse fibroblasts grown in culture were investigated . Long incubations (20 h) with the antibiotic caused a higher degree of inhibition of sugar incorporation into glycoproteins in transformed cells . However, the formation of lipid-linked intermediates was inhibited to a similar level in both cell types . When time dependent inhibition experiments were carried out using transformed cells, an earlier and stronger inhibition of the formation of lipid-oligosaccharides occurred (70% inhibition at 30 min) . In 3T3 cells, prolonged incubation (6-8 h) was necessary in order to reach a similar degree of inhibition . Formation of lipid-sugar was also inhibited to a greater extent by B2-tunicamycin in transformed cells . This inhibition was not clearly time dependent . Analysis of the newly synthesized glycolipids in 3T3 and in transformed cells after B2-tunicamycin treatment have shown reduction in dolichyl-P-P-sugars as well as in other glycolipids . Dimethylsulfoxide (10%) and linoleic acid (0.5 mg/ml) markedly increased the level of tunicamycin activity in 3T3 cells while phosphatidylcholine (2 mg/ml) partially reversed it . The stronger and faster inhibition of the formation of lipid intermediates of the dolichyl-phosphate cycle caused by B2-tunicamycin in transformed cells, described here for the first time, may therefore be due to differences in penetration of the antibiotic into these cells. J Antibiot (Tokyo), 1985 May, 38(5), 642 - 8 Biological activity of cadeguomycin . Inhibition of tumor growth and metastasis, immunostimulation, and potentiation of 1-beta-D-arabinofuranosylcytosine; Yuan BD et al.; Cadeguomycin retarded growth of sc solid IMC carcinoma in CDF1 mice, and pulmonary metastasis of Lewis lung carcinoma in C57BL/6 mice . The antibiotic enhanced phagocytic activity of murine peritoneal macrophages and IL-1 production by P388D1 cells . Delayed type hypersensitivity was stimulated and interferon was induced by the drug . The results suggest that cadeguomycin inhibits tumor growth and metastasis in association with modification of the immune system . The cytotoxicity of arabinosylcytosine to K562 and YAC-1 cells was markedly enhanced by cadeguomycin in culture . The combined administration of arabinosylcytosine and cadeguomycin displayed potentiation in the inhibition of growth of ip-implanted P388 leukemia and metastasis of sc-implanted P388 leukemia to the regional lymph nodes . Cadeguomycin showed low toxicity for mice. Cell Biol Int Rep, 1985 May, 9(5), 471 - 7 Histochemical detection of DNA strand scissions in mammalian cells by in situ nick translation; Iseki S et al.; A method to visualize in situ of single strand scissions of DNA in fixed mammalian cells has been developed . Using the nuclear nick translation with biotin-labeled dUTP followed by binding to avidin-biotin-peroxydase complex, the nuclei of HeLa cells which had been treated with a DNA-damaging antibiotic bleomycin were specifically stained, implicating that the histochemical detection of single strand scissions (nicks) of DNA in fixed cells was completed without destroying the morphology, and without using autoradiography. Nucleic Acids Res, 1985 Apr 11, 13(7), 2305 - 23 A comparison of the structure of echinomycin and triostin A complexed to a DNA fragment; Ughetto G et al.; Two members of the quinoxaline antibiotic family, echinomycin and triostin A, form crystals complexed to a DNA fragment with the sequence d(CpGpTpApCpG) . The crystal structure of both complexes was solved by X-ray diffraction to near-atomic resolution . The two structures are similar to each other with differences in some details due to the shorter cross bridge of echinomycin . Both molecules act as bis intercalators surrounding the d(CpG) sequence at either end of the double helix . Alanine forms sequence-specific hydrogen bonds to guanines in the minor groove . The two central AT base pairs are held together by Hoogsteen base pairing with adenine in the syn conformation in both complexes . An octahedrally hydrated magnesium ion is found in the crystal lattice that plays an important role in organizing the lattice as well as stabilizing the complex by hydrogen bonding both to base pairs of DNA and to the quinoxaline ring nitrogen atoms in the major groove side of the DNA double helix . A functional description of the various amino acids in quinoxaline antibiotics is given, together with possible modifications that might affect biological activity. Biochemistry, 1985 Apr 9, 24(8), 2022 - 7 Gramicidin S synthetase . Temperature dependence and thermodynamic parameters of substrate amino acid activation reactions; Vater J et al.; In the biosynthesis of the cyclic decapeptide antibiotic gramicidin S, the constituent amino acids are activated by a two-step mechanism involving aminoacyl adenylate and thio ester formation which are both reversible processes . The dissociation constants (KD) for the gramicidin S synthetase-substrate amino acid-thio ester complexes are 100-1000-fold lower compared to the KM data of the preceding aminoacyl adenylate reactions . The affinity for these substrates is appreciably higher at the thio template sites than at the aminoacyl adenylate reaction centers . Therefore, the activation equilibria are quantitatively shifted toward thio ester formation . A set of thermodynamic parameters for the activation processes was determined from the temperature dependence of the KM and KD data . Reaction enthalpies were obtained from a van't Hoff analysis of these constants . delta G degree for the substrate activation reactions of the heavy enzyme of gramicidin S synthetase (GS 2) is predominantly controlled by entropy contributions . In contrast, the overall activation and concomitant racemization of phenylalanine by phenylalanine racemase (GS 1) are exothermic processes which are distinguished by a small negative reaction entropy. S Afr Med J, 1985 Apr 6, 67(14), 559 - 60 Hepatic abscess in a patient with polycystic liver disease . A case report; du Toit DF et al.; A patient with a liver abscess and underlying polycystic renal and liver disease is described . The liver abscess was diagnosed on the clinical findings and accurately localized by ultrasonography . Tube drainage and antibiotic administration resulted in a rapid recovery . The polycystic liver disease, which was previously undiagnosed and asymptomatic, was an unexpected finding at laparotomy. Pathology, 1985 Apr, 17(2), 204 - 8 Forms of colitis--a review of recent developments; Whitehead R; Recent advances in the accessibility of the bowel and in techniques for the study of colonic pathology have resulted in descriptions of several forms of colitis which were previously unrecognized and in elucidation of the etiology of previously described but poorly understood entities . Present knowledge of antibiotic-associated colitis, colitis indeterminate, acute self-limited colitis, collagenous colitis and the colitis of food allergy is reviewed. Jpn J Antibiot, 1985 Apr, 38(4), 987 - 94 {Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology}; Yamamoto T et al.; Fundamental and clinical studies on cefpimizole (AC-1370), a new cephem antibiotic, were performed and the following results were obtained: Concentration of AC-1370 was examined in serum, internal genital organs and retroperitoneal fluid after single intravenous administration of 2.0 g dose . The venous serum level of AC-1370 was 243 micrograms/ml at 30 minutes after the administration . The sufficient transfer of AC-1370 to internal genital organs and retroperitoneal fluid was recognized . In clinical trial, AC-1370 was given to 10 cases with obstetrical and gynecological infections . The efficacy was evaluated as good in 8 cases and poor in 2 cases . No side effects were observed in any of the cases treated with AC-1370. Jpn J Antibiot, 1985 Apr, 38(4), 926 - 39 {Pharmacokinetics and clinical studies on cefpimizole in the field of obstetrics and gynecology}; Cho N et al.; Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained . The absorption and tissue penetration of AC-1370 into intrapelvic genital organs were good . The peak serum level in the uterine artery after an intravenous drip infusion for 30 minutes was 49.0 micrograms/ml . High concentrations were obtained also in genital organ tissues; the maximum concentrations were 24.4 approximately 39.0 micrograms/g after an intravenous drip infusion . The changing patterns of the tissue concentrations were similar to those in the serum . The penetration of AC-1370 into intrapelvic dead space exudate was good . The level reached a peak of 35 micrograms/ml at 2 approximately 4 hours after an intravenous drip infusion with 1 g and 3.7 micrograms/ml after 12 hours . AC-1370 was effective in 20 out of 21 cases (95.2%) with gynecoobstetrical infections such as intrauterine, intrapelvic infection and mammitis, administered with 1 approximately 2 g twice a day . Few side effects were observed. Jpn J Antibiot, 1985 Apr, 38(4), 911 - 4 {Clinical efficacy of cefpimizole in inflammatory diseases in the field of gynecology}; Okamura K et al.; Clinical study to evaluate the usefulness of cefpimizole (AC-1370) was made in the 6 patients with female genital organ infections . Two grams or 4 g of AC-1370 was administered a day by intravenous drip infusion ranging from 5 to 18 days . Responses were excellent in 2 cases, good in 3 cases and poor in 1 case, parametritis after hysterectomy . The efficacy rate was 83% . Neither general side effect nor abnormal laboratory finding was observed . AC-1370 showed a satisfactory clinical efficacy in treatment of the infections in the field of gynecology, and it has been concluded that AC-1370 will be an useful antibiotic for these infections. Jpn J Antibiot, 1985 Apr, 38(4), 1017 - 21 Clinical study of cefpimizole in obstetric and gynecologic infections; Sugiyama T et al.; The use of cefpimizole (AC-1370) in 11 patients with a variety of obstetric and gynecologic infections was studied . Although the activity of AC-1370 was found in vitro less eminent than those of currently employed antibiotic regimens, the overall clinical response was 82% . No side effects were found. Jpn J Antibiot, 1985 Apr, 38(4), 1011 - 6 {Fundamental and clinical studies on cefpimizole in the field of obstetrics and gynecology}; Yamamoto K et al.; Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, fundamentally and clinically . And the following results were obtained . The concentrations of the drug in uterine arterial and cubital venous blood, and internal genital organs following intravenous drip infusion were measured . The results demonstrated favourable transfer of the drug into the various internal genital organs . Four patients with obstetric and gynecological infections were treated with AC-1370 . The therapeutic results were good in 3, and poor in 1 case, therefore the effective rate was 75% . No side effects were noted in any cases, but the severe eosinophilia (37%) was found in 1 patient . It is therefore presumed that AC-1370 is a useful drug for infectious diseases in the field of obstetrics and gynecology. J Pharmacobiodyn, 1985 Apr, 8(4), 270 - 7 Preparation and biopharmaceutical evaluation of microcapsules of ampicillin; Goto S et al.; Microencapsulation of ampicillin, an orally administered antibiotic, with different viscosity grades of ethyl cellulose was studied . The preparation of microcapsules was done as follows; the mixture of ethyl cellulose-CH2Cl2-ampicillin was dispersed in purified water containing 0.5% (w/w) sodium lauryl benzenesulfonate, and then CH2Cl2 was dried out by elevating the temperature . The dissolution curves for the release of ampicillin from microcapsules prepared using the four different viscosity grades of ethyl cellulose were quite different . The release of ampicillin increased with decreasing ethyl cellulose viscosity . The evaluation of prepared microcapsules was made using gastric-emptying-controlled rabbits . The plasma concentration of ampicillin obtained by the administration of microcapsules showed a significant sustained-release pattern . The area under the plasma concentration curve (AUC) of ampicillin obtained after a single oral administration of microcapsules prepared using 10 cps ethyl cellulose was 1.8 times greater than that obtained after double oral administration of powder . This fact will be caused by the delaying of gastric-emptying, intestinal-transit and dissolution of ampicillin there . It was confirmed that a large number of microcapsules still remained in the stomach and each microcapsules still contained ampicillin at 24 h after dosing from the experiment using gastric-emptying-controlled rabbits. Antibiot Med Biotekhnol, 1985 Apr, 30(4), 264 - 71 {Regulation of heliomycin biosynthesis by the carbon source}; Vinogradova KA et al.; The effect of different carbon sources on the biosynthesis of heliomycin by Streptomyces olivocinereus 11-98 was studied . Inverse relationship between the culture growth rate and the biosynthesis of heliomycin in the media with different sugars was shown . Arabinose and glucose provided the highest culture growth rate, while the levels of the antibiotic biosynthesis were the lowest . With the use of lactose the culture growth rate was the lowest and the antibiotic biosynthesis level was the highest . The level of the antibiotic biosynthesis was determined not only by the culture growth rate but also by the nature of the carbon source . With the use of glucose repression of heliomycin biosynthesis was much lower than that with the use of arabinose, while the culture growth rates were similar . Addition of glucose to the medium with lactose resulted in increasing of the antibiotic biosynthesis as long as the glucose concentration in the medium increased . Glycerol proved to be the most favourable carbon source for the biosynthesis of heliomycin . It also provided a comparatively high rate of the culture growth . Arabinose inhibited the antibiotic synthesis in the medium with glycerol and the inhibition level rose with an increase in the arabinose concentration . It is suggested that regulation of heliomycin biosynthesis is of the "glucose effect" type. Chir Ital, 1985 Apr, 37(2), 174 - 82 {Acute appendicitis: clinico-diagnostic and therapeutic considerations}; Carditello A et al.; Since january 1970-december 1982, 58 patients underwent emergently appendectomy for acute appendicitis . 31 (53,4 percent) where males; the average age was 21 +/- 2,3 years (M +/- SEM) . The duration of symptoms ranged from 1-6 hours (10,3 percent of cases) to over 48 hours, before the hospital admission (15,4 percent of cases) . 27 patients (46,5 percent) had a clinical examination at home by a physician . 21 patients (36,4 percent) came to hospital emergency unit without previous physical examination; 10 (17,2 percent) were transferred from other departments . In 6,9 percent of cases was present a perforated appendicitis with peritonitis . During operation, in 50 percent of patients was performed a therapeutic peritoneal lavage . In 63,7 percent of cases multiple drains were placed in peritoneal cavity . In all patients was effected postoperative antibiotic profilaxis . The mortality rate was 3,4 percent . General complications were observed more in patients with perforated appendicitis . This review suggests the following remarcable data: morbidity of this disease is still high; the physical examination is more important than laboratory work (especially in the elderly patients, which are often immunodepressed and in children, with leucocitosis-lack at hospital admission); early surgery is the most important factor to the improvement of prognosis in these cases and the results of surgical treatment are improved by large vertical incisions, peritoneal lavage and application of multiple intracavitary drains. Am J Hosp Pharm, 1985 Apr, 42(4), 839 - 43 Compatibility of clindamycin phosphate with cefotaxime sodium or netilmicin sulfate in small-volume admixtures; Foley PT et al.; The stability and compatibility of clindamycin phosphate plus either cefotaxime sodium or netilmicin sulfate in small-volume intravenous admixtures were studied . Admixtures containing each drug alone and two-drug admixtures of clindamycin phosphate plus cefotaxime sodium or netilmicin sulfate were prepared in 100 mL of 5% dextrose injection and 0.9% sodium chloride injection in both glass bottles and polyvinyl chloride (PVC) bags . Final concentrations of clindamycin, cefotaxime, and netilmicin were 9, 20, and 3 mg/mL, respectively . All solutions were prepared in duplicate and stored at room temperature (24 +/- 2 degrees C) . Samples were visually inspected, tested for pH, and assayed for antibiotic concentration using stability-indicating assays at 0, 1, 4, 8, 16, and 24 hours for admixtures in glass bottles and at 0, 8, and 24 hours for admixtures in PVC bags . No substantial changes in color, clarity, pH, or drug concentration were observed in any of the solutions . Clindamycin phosphate is compatible with cefotaxime sodium or netilmicin sulfate in 5% dextrose and 0.9% sodium chloride injections in glass bottles or PVC bags for 24 hours. Drug Intell Clin Pharm, 1985 Apr, 19(4), 293 - 6 Pitfalls in the delivery of outpatient intravenous therapy; Goldenberg RI; Recent articles promoting the advantages of intravenous antibiotic therapy and total parenteral nutrition for use in home health care patients have spawned a multitude of commercial and hospital-based programs dedicated to providing such therapies in outpatient settings . Only since the establishment of these programs has there evolved an increasing familiarity with adverse experiences and pitfalls in the provision of outpatient care . Significant errors have been made in the areas of patient and disease admission criteria, antibiotic regimens, medicolegal concepts, medical and hospital politics, and financial reimbursement . This article explores the pitfalls intrinsic to the delivery of outpatient parenteral therapies and focuses on the need for diligence in program coordination, multidisciplinary involvement, and education in averting those pitfalls. Ann Neurol, 1985 Apr, 17(4), 350 - 5 Decreased morbidity from acute bacterial spinal epidural abscesses using computed tomography and nonsurgical treatment in selected patients; Leys D et al.; We describe 5 patients with spinal epidural abscesses in whom computed tomographic scanning confirmed diagnosis without the use of myelography . One patient required urgent surgery because of rapidly deteriorating neurological status, but the other 4 were treated nonsurgically . The medical treatment of these patients and 9 others described in the literature consisted of antibiotics administered parenterally for a minimum of 8 weeks, followed by oral antibiotic therapy . Early diagnosis with computed tomographic scanning and a benign neurological state at the onset of treatment were associated with good results. Dis Colon Rectum, 1985 Apr, 28(4), 264 - 6 Cocaine colitis . Is this a new syndrome? Fishel R, Hamamoto G, Barbul A, Jiji V, Efron G. An unusual case of colitis in a 37-year-old cocaine addict is described . The patient presented with right-sided abdominal pain and diarrhea exacerbated by his use of cocaine . Significant antibiotic ingestion was denied . At laparotomy, an edematous cecum and ascending colon were found, the cut surface of which revealed diffuse superficial ulcerations and yellowish fibrinous material . Microscopic examination demonstrated findings consistent with pseudomembranous colitis with an ischemic component . A mechanism involving catecholamine-induced mucosal ischemia is postulated to explain the findings seen in this patient. Drug Intell Clin Pharm, 1985 Apr, 19(4), 291 - 2 Health care cost-containment in a changing health care world; Tanner DJ; Home health care, particularly antibiotic home health care, must be studied against a background of change . Hospitals are changing their structure as one way of coping with health care costs . The Health Care Financing Administration is making its impact with the DRG program . As a result, hospitals are seeking various means of cost containment, and home health care is seen as one possible answer . Much of the potential benefit to be derived from home health care will depend on how thoroughly it is based on good modern technology, and how carefully it is planned to reduce hospital length of stay and to decrease the costs of hospital personnel and supplies . Another answer may be found in the administration of parenteral antibiotics by once-daily doses. Am J Dis Child, 1985 Apr, 139(4), 375 - 7 Necrotizing entercolitis . Variables associated with the severity of disease; Barnard JA et al.; The medical records of 51 inborn infants with necrotizing enterocolitis (NEC) were studied to determine factors that may contribute to the severity of NEC . In contrast to infants requiring only medical intervention, those with severe disease requiring a surgical procedure were less likely to have a history of a symptomatic patent ductus arteriosus (14% v 45%); they also required fewer days of antibiotic therapy (three v five) and fewer days of endotracheal intubation (0.5 v three) . They were fed earlier (two days v four days) . The diagnosis was made at a younger age in infants needing surgery (6.5 days v 14 days) . These data indicate that infants with minimal neonatal morbidity may be at risk for severe NEC, which results in bowel necrosis. Can J Ophthalmol, 1985 Apr, 20(3), 105 - 9 Adjustable-suture strabismus surgery: a review of 255 consecutive cases; Pratt-Johnson JA; Adjustable-suture strabismus surgery was performed on 255 patients under general anesthesia . Prophylactic topical and oral antibiotic therapy was used in all cases; only one postoperative infection occurred . Adjustments were needed for 123 patients and were done under topical tetracaine anesthesia within a few hours after recovery from general anesthesia . Overall the adjustments appeared to be reliable . The use of droperidol, however, made reliable adjustment impossible in two cases and is therefore strongly contraindicated if suture adjustment is to be done within a few hours of general anesthesia . There were two cases of temporary palsy of the muscle with the adjustable suture, presumed to be due to the topical anesthetic . Unexpectedly large effects of the surgery occurred in three cases of acquired sixth cranial nerve palsy in which full abduction had been recovered but a concomitant esotropia remained and in a few cases in which the muscles had previously been resected and there were normal active ductions preoperatively . Contraindications to the use of adjustable sutures in strabismus surgery may include multiple orbital fractures, previous orbital floor decompression for dysthyroid ophthalmopathy, and a variable angle. Sex Transm Dis, 1985 Apr-Jun, 12(2), 72 - 5 Prophylaxis with lymecycline in induced first-trimester abortion: a clinical, controlled trial assessing the role of Chlamydia trachomatis and Mycoplasma hominis; Heisterberg L et al.; PIP: A clinical, controlled trial was performed to study the effect of prophylaxis with lymecycline and the role of Chlamydia trachomatis and Mycoplasma hominis in postabortal genital infection . Of 532 women who were to undergo 1st trimester abortion, 269 were randomized to treatment with oral lymecycline (300 mg bid) starting 2 days before the abortion and continuing for a total of 7 days, and 263 were randomized to placebo treatment . The rate of postabortal infection was 9.3% in the antibiotic group and 9.5% in the placebo group, an insignificant difference (P greater than .8) . The presence of C . trachomatis in the cervix/urethra at the time of abortion showed a significant association with the occurrence of postabortal infection (P less than .005), but there was no correlation between the effect of treatment and the presence of infection (P greater than .4) . The presence of M . hominis, a history of pelvic inflammatory disease, maternal age, gestational age, the number of births, spontaneous and induced abortion, and the Hegar number showed no significant association with postabortal infection (all P values greater than .05) . It is recommended that women who are to undergo induced abortion be examined for the presence of C . trachomatis and treated, as they constitute a risk group . author's modified Biochem Pharmacol, 1985 Apr 1, 34(7), 1079 - 86 Sensitivity of adipocyte basal and insulin-stimulated hexose transport to the membrane lipid structure; Hutchinson BT et al.; A series of anesthetic alcohols inhibited basal and insulin-stimulated 2-deoxy-D-{1-14C}glucose transport in adipocytes over total alcohol concentration ranges that cause local anesthesia of rat sciatic nerve . The relative potencies of the inhibition caused by the alcohols increased in the following order: methanol less than ethanol less than propanol less than butanol less than benzyl alcohol less than hexanol less than octanol . The inhibition was reversible and correlated well with the known partitioning of the alcohols into lipids of biological membranes . Adipocyte membranes were labeled with the 5-nitroxide stearate spin probe to investigate the effects of the alcohols on the dynamic structure of membrane lipids of the adipocyte . The alcohols increased the membrane "fluidity", and the relative concentration dependence of the effects closely paralleled that noted from methanol to octanol in transport studies . Alcohols from methanol to hexanol caused inhibition of hexose transport at molar potencies comparable to that observed for membrane disordering . This suggests that hydrophobic regions of the transporter and its lipid environment are perturbed by a comparable mechanism for each alcohol . The cholesterol-complexing polyene antibiotic filipin inhibited hexose transport and influenced the mobility of lipid domains sampled with the nitroxide cholestane, cholesterol-like spin probe . The data are consistent with the concept that the membrane structural/functional effects are mediated by formation of 1:1 cholesterol:filipin complexes . Alcohols and filipin inhibited inherent transporter activity and perturbed the membrane lipid structure without dramatically diminishing transport stimulation by insulin above basal . The specific organization of membrane lipids (particularly cholesterol) may provide an essential environment for optimal transport system activity. Br J Oral Maxillofac Surg, 1985 Apr, 23(2), 128 - 34 Actinomycosis of the parotid gland; Hensher R et al.; Primary parotid actinomycosis is extremely rare . Two patients are discussed in whom this disease presented quite differently . The literature is reviewed and the management described, with particular reference to antibiotic therapy. Vet Clin North Am Equine Pract, 1985 Apr, 1(1), 131 - 49 Respiratory problems in foals; Beech J; Despite major advances in our knowledge and ability to treat respiratory diseases in neonatal foals, neonatal respiratory medicine is still in its infancy . It is hoped that this article may serve as a guideline for diagnosis and treatment . Specific antibiotic regimens and emergency procedures are covered in other articles in this symposium . Because management factors play a critical role in the pathogenesis of respiratory disease, education of clients as to their importance would help both prophylactically and therapeutically . The necessity of very careful monitoring of neonates, which is critical to early detection of disease, should be stressed . As respiratory diseases can be fulminant and rapidly fatal, it is imperative not to delay diagnosis and therapy . Thorough examination and implementation of appropriate diagnostic techniques, as well as prompt early referral to a more sophisticated facility when indicated, would prevent many deaths . Although sophisticated support systems are vital for survival of some of these foals, good basic intensive nursing care combined with selection of appropriate drug therapy very early in the course of the disease is all that many foals require and can significantly improve survival rates. Boll Soc Ital Biol Sper, 1985 Mar 30, 61(3), 357 - 63 {Action of aminoglycosides on platelet aggregation in vitro}; Nubile G et al.; The authors tested the influence of gentamicin, spectinomycin dihydrostreptomycin on the ADP and epinephrine in vitro induced platelet aggregation . Our aim was to demonstrate if platelet aggregation in vitro had some influences by antibiotics . A reduction in platelet aggregability, strictly dependent from the used antibiotic dose was observed . We have studied platelet function thanks to Born's method, adding to PRP gradual therapeutics doses of antibiotics . The results showed a reduction of platelet function which was dose-depended, and, particularly, gentamicin seemed to be the most effective among aminoglycosides . An interference between these drugs and the ADP and epinephrine binding to specific platelet receptor sites is proposed. Biochim Biophys Acta, 1985 Mar 29, 839(1), 16 - 25 A resonance Raman study on the interaction of rifampicin with Escherichia coli RNA polymerase; Johnson RS; The technique of resonance Raman spectroscopy has been used to investigate the interaction of the antibiotic rifampicin with Escherichia coli RNA polymerase . Spectra were analyzed by generating the first derivative of each recorded spectrum using the Savitsky-Golay algorithm . The only band that shifted significantly in the resonance Raman spectrum of rifampicin upon the formation of the drug-core polymerase complex was the amide III band . It underwent an 8 cm-1 shift from 1306 cm-1 in aqueous solution to 1314 cm-1 . A comparable shift was observed for the rifampicin-holoenzyme complex . Thus, the interaction of the sigma subunit with the core polymerase does not significantly alter the manner in which rifampicin interacts with RNA polymerase . The nature of this shift has been analyzed further by recording the resonance Raman spectrum of rifampicin in a variety of solvents with different hydrogen-bonding solvents (benzene and carbon disulfide) the amide III band was observed at approximately 1220 cm-1; in dimethyl sulfoxide, a weak hydrogen-bond acceptor, 1274 cm-1; in water, a strong hydrogen-bonding solvent, 1306 cm-1; and finally, in triethylamine, a stronger hydrogen-bonding solvent than water, it was observed at 1314 cm-1 . Thus, as the hydrogen-bonding ability of the solvent increased, the amide III band shifted to higher frequency . Based on these results, the rifampicin binding site in RNA polymerase provides a stronger hydrogen-bonding environment for the amidic proton of rifampicin than is encountered when rifampicin is free in aqueous solution. Schweiz Med Wochenschr, 1985 Mar 16, 115(11), 378 - 80 {Invasive pulmonary aspergillosis--a diagnostic and therapeutic problem in patients with severe aplastic anemia}; Osterwalder B et al.; Three young patients with severe aplastic anemia undergoing intensive immunosuppressive therapy developed fever and pulmonary infiltrates during longlasting severe granulocytopenia, despite multiple broad spectrum antibiotic combinations and granulocyte transfusions . Invasive pulmonary aspergillosis was diagnosed only by thoracotomy . In conjunction with high dose amphotericin-B therapy complete resolution of aspergillosis was achieved in two cases, paralleled by slow recovery of bone marrow function, whereas in the third case only a partial remission was possible together with transient amelioration of granulopoiesis . We suggest early aggressive surgical methods to establish the diagnosis of aspergillosis in these severely menaced patients, so that antifungal therapy with high dose amphotericin-B can be initiated at an early stage. Toxicol Appl Pharmacol, 1985 Mar 15, 77(3), 479 - 89 Comparative ototoxicity of netilmicin, gentamicin, and tobramycin in cats; McCormick GC et al.; Netilmicin, a semisynthetic aminoglycoside antibiotic, is less ototoxic in a variety of species than other aminoglycosides currently in therapeutic use . In this study, mixed-breed cats (four/group) were given daily sc injections of netilmicin (20, 40, and 80 mg/kg), gentamicin (20 and 40 mg/kg), or tobramycin (20, 40, and 80 mg/kg) for up to 30 weeks or until ototoxicity was observed . The animals were examined throughout the study for effects on cochlear and vestibular function . Hematologic, serum chemical, and drug-serum (24-hr postdose) assays were performed at approximate monthly intervals during the dosing period . The cochleae, kidneys, and liver were examined microscopically . The mean number of dose days required to produce vestibulotoxic effects, demonstrated by impaired righting reflex or locomotor ataxia, was from 41 to 61 in cats dosed with tobramycin (40 and 80 mg/kg) or gentamicin . No vestibular dysfunction was observed in any of the netilmicin 20-mg/kg-dosed cats, in two cats each of the tobramycin 20-mg/kg and netilmicin 40-mg/kg groups, and in one netilmicin 80-mg/kg-dosed animal . Histologic examination of the cochleae revealed degeneration of the hair cells and supporting sensory structures in the majority of cats dosed with gentamicin at 20 and 40 mg/kg and tobramycin at 40 and 80 mg/kg . Less than 50% of the tissues from cats of the tobramycin 20-mg/kg and netilmicin 40- and 80-mg/kg-dosed groups had similar degenerative cochlear changes . No cochlear damage was noted in any of the cats given netilmicin at 20 mg/kg . Results of the clinical laboratory determinations were generally unremarkable . Proximal tubular degeneration was the principal finding observed in the kidneys of the animals . Under the conditions of this study, at least a twofold (vestibular) to fourfold (cochlear) relative safety margin for ototoxicity was established in favor of netilmicin over tobramycin and gentamicin. Experientia, 1985 Mar 15, 41(3), 419 - 20 Thiarubrine A, a bioactive constituent of Aspilia (Asteraceae) consumed by wild chimpanzees; Rodriguez E et al.; Two African species of Aspilia (Asteraceae), which are used medicinally by man and which are eaten by wild chimpanzees in an unusual manner, were found to contain the potent antibiotic thiarubrine A as a major leaf phytochemical . Its presence in leaf material strengthens the view that the feeding behavior of wild chimpanzees is related to special physiological or pharmacological effects on the animals. J Biol Chem, 1985 Mar 10, 260(5), 2884 - 9 Rates of amphotericin B and filipin association with sterols . A study of changes in sterol structure and phospholipid composition of vesicles; Clejan S et al.; The influence of structural modifications in sterols and phospholipids on the rate of polyene antibiotic-sterol interaction was studied . For filipin and amphotericin B association with sterols in vesicles, a preferential interaction was found with sterols whose side chain length is close to that of cholesterol . Introduction of trans double bonds into the sterol side chain did not alter the rate of interaction in vesicles . The delta 7-bond of the sterol appears to be of critical importance in amphotericin B-sterol interaction, whereas the delta 5-bond is not essential . These observations are relevant to the well-known effects of amphotericin B on cell membranes containing ergosterol compared with those containing cholesterol . The dependence of the rates of sterol-polyene antibiotic interaction on the phospholipid composition of the vesicles indicates that phospholipid vesicles may be an inadequate model for reaching a comprehensive understanding of the effects exerted on biological membranes by these agents. J Infect, 1985 Mar, 10(2), 143 - 57 Pneumococcal meningitis: an evaluation of prognostic factors in 164 cases based on mortality and on a study of lasting sequelae; Bohr V et al.; During the period 1966-76, 164 patients with pneumococcal meningitis were admitted to the University Hospital, Copenhagen . Of 111 survivors 94 underwent a series of clinical examinations . The findings in each patient were assessed for their aetiological relationship to meningitis . Of these patients 54% had neurological sequelae, 42% had neuropsychological sequelae, 25% had otological sequelae and 16% had sequelae as judged by computer-assisted tomography of the brain . On the basis of the general clinical condition, each patient was evaluated for the presence of sequelae of meningitis by means of a rating of nil, mild, moderate or severe . These ratings and mortality rates were used to evaluate the prognostic significance of various features present during the acute illness . A fatal outcome was significantly associated with increasing age, concomitant pneumonia, altered consciousness on admission, transfer from another hospital and development of complications while in hospital . There was a statistically significant association between lasting sequelae and the female sex, the age group of 16-50 years, patients who had not received any pre-admission antibiotic therapy and those with positive bacterial cultures of specimens from sites other than blood or cerebrospinal fluid. Comput Radiol, 1985 Mar-Apr, 9(2), 101 - 4 Disseminated histoplasmosis diagnosed by computed tomography directed needle biopsy of an adrenal mass; Berdeaux DH et al.; Disseminated histoplasmosis was diagnosed by a computed tomographic (CT) directed needle biopsy of an adrenal mass . A 53-year-old man presented with a nonproductive cough, bilateral flank discomfort, and constitutional symptoms . Physical exam revealed mild hepatomegaly and tenderness . Chest radiograph revealed two destructive bone lesions . An abdominal CT scan demonstrated bilateral adrenal masses . Needle biopsy of the left adrenal mass revealed histoplasmosis . A rib resection or exploratory laparotomy was avoided . He has been completely free of evidence of disease for 6 months following completion of antibiotic therapy. Klin Wochenschr, 1985 Mar 1, 63(5), 225 - 9 Epidural opiates: long-term experiences in cancer pain; Zenz M et al.; Epidural opiates were administered to 139 patients with pain due to malignant diseases via a chronic indwelling catheter inserted percutaneously . So far, 9,716 days of treatment can be evaluated . In 87% of the patients whose pain previously could not be controlled with conventional analgesic approaches, epidural opiates resulted in remarkable pain relief . With a mean daily dose of 15.6 mg morphine (range 2-290 mg) or 0.86 mg buprenorphine (range 0.15-7.2 mg) half of the patients could be treated as outpatients . The mean duration of therapy was 72 days (range 1-700 days), 26 catheters being in place for more than 100 days and one catheter being in place for 510 days . Two severe side-effects (meningitis) were observed, both patients being free of symptoms after catheter removal and antibiotic therapy . Epidural opiates proved to be a valuable method of pain control in terminal illness . The method should be reserved for those patients, for whom oral opiates fail to produce effective pain relief. J Vet Pharmacol Ther, 1985 Mar, 8(1), 55 - 61 Treatment of Moraxella bovis infections in calves using a long-acting oxytetracycline formulation; George LW et al.; Studies were undertaken to determine the effectiveness of an oxytetracycline HCl formulation for the prophylaxis and treatment of chronic Moraxella bovis ocular infections in calves .