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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 . Two separate experiments were performed . For the first, calves were separated into two groups and the eyes were infected with M . bovis . The eyes of these calves were observed and cultured for 37 consecutive days . On the 37th and 40th day, each of the five calves were treated intramuscularly with the drug (20 mg/kg of body weight) . The other five calves (second group) remained untreated as controls . The cultures from the five treated calves were negative after the first antibiotic administration and remained so for 14 days . M . bovis was isolated from each eye of the control calves at least once during that time . None of the antibiotic-treated calves was completely resistant when reinfected with M . bovis . For the second experiment, calves were given a prophylactic administration of the formulation and were then infected with M . bovis 48 (n = 4 calves) or 72 (n = 4 calves) h later . These treatments resulted in a lower incidence of keratoconjunctivitis and a decreased duration of bacterial shedding, as compared to controls (n = 8 calves), but did not completely prevent the occurrence of disease or the establishment of ocular infections. J Foot Surg, 1985 Mar-Apr, 24(2), 116 - 21 Gentamicin-impregnated PMMA beads: an introduction and review; Marcinko DE; The local implantation of gentamicin-impregnated polymethylmethacrylate beads, in conjunction with the application of consistent surgical principles, has been used in Europe for the past decade . The system has proved successful in the treatment of osteomyelitis and soft tissue infections . It combines the benefits of high local antibiotic tissue levels with the achievement of primary wound closure . In this presentation, the advantages, disadvantages, and technical application of this new drug delivery system is introduced to the profession for consideration and future use. J Clin Pharmacol, 1985 Mar, 25(2), 89 - 94 The excretion of rosaramicin in breast milk; Stoehr GP et al.; The excretion of rosaramicin, a macrolide antibiotic, was studied in the breast milk of ten lactating women . Breast milk and serum samples were collected for 48 hours after a single 250-mg oral dose of rosaramicin . Mean serum half-life, apparent volume of distribution, and oral clearance were 4.4 hours, 3.41 L/kg, and 6.34 mL/min/kg, respectively . Mean milk/serum ratio was 0.12 and the total amount of drug recovered over the first ten hours was 6.25 micrograms, approximately 0.0025% of the dose . A positive correlation between breast milk volume and breast milk clearance was found, suggesting that the amount of drug received by a nursing infant will depend on the volume of milk produced by the mother . Drug-induced toxicity from the parent drug is unlikely to occur in nursing infants since the amount of rosaramicin that a nursing infant could ingest is small. Thorax, 1985 Mar, 40(3), 184 - 6 Adverse reactions to piperacillin in adults with cystic fibrosis; Stead RJ et al.; Nine adult patients with cystic fibrosis, nearly a quarter of the 38 patients with this disease who were treated with piperacillin (59 courses in all) during 1981-3 at the Brompton Hospital, developed a swinging pyrexia after a mean of 13.5 days' treatment with this antibiotic . The fever resolved shortly after the piperacillin treatment was stopped, as did the widespread rashes in the two patients who developed them . Three of four patients who had probable reactions to azlocillin may have been sensitised by piperacillin . As piperacillin does not appear to be any more effective than other antipseudomonal penicillins in cystic fibrosis, it is no longer used at the hospital for treating bronchopulmonary exacerbations in such patients. Neurosurgery, 1985 Mar, 16(3), 304 - 8 Developments in the treatment and prognosis of multiple cerebral abscesses; Rousseaux M et al.; Multiple cerebral abscesses have been recognized with increasing frequency because of the use of computed tomography and have been the subject of various therapeutic proposals . Their prognosis has been considerably improved thanks to high dose antibiotic therapy . However, diagnostic and therapeutic problems persist. J Infect Dis, 1985 Mar, 151(3), 528 - 34 Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis; Tauber MG et al.; A study was made of the effects of antibiotics and corticosteroids on parameters that reflect brain dysfunction and potential neurological damage in experimental pneumococcal meningitis in rabbits . Brain water content was 398 +/- 10 g/100 g dry weight in normal rabbits and 410 +/- 11 g in rabbits after 24 hr of infection (P less than .001) . Cerebrospinal fluid (CSF) lactate levels increased from 16.3 +/- 3.4 mg/dl to 69.5 +/- 28.2 mg/dl (P less than .001), and CSF pressure increased by +8.3 +/- 3.6 mm Hg (P less than .005) over the same interval . Antibiotic therapy with ampicillin sterilized CSF and normalized CSF pressure and brain water content in all animals within 24 hr, while CSF lactate levels remained elevated . Administration of methyl prednisolone, 30 mg/kg, or dexamethasone, 1 mg/kg, 15 and 22 hr after infection completely reversed the development of brain edema, but only dexamethasone also significantly reduced the increase in CSF lactate level (43.8 +/- 12.3 mg/dl) and CSF pressure (+1.8 +/- 2.7 mm Hg) . Methyl prednisolone did not significantly affect pressure or lactate levels. Can Med Assoc J, 1985 Mar 1, 132(5), 529 - 31 Esophageal duplication cyst containing a foreign body; Stringel G et al.; About 10% to 15% of all duplication cysts in the alimentary tract are esophageal . Esophageal duplication cysts are intimately attached to the alimentary tract, are lined by mucous membrane and have smooth muscle . This paper describes a 2-year-old child who presented with symptoms of progressive respiratory distress . A diagnosis of esophageal duplication cyst was made . At surgery a low cervical incision was made and the sternal manubrium split, thereby providing adequate exposure . The cyst was then removed . The most useful investigations were chest roentgenography and barium esophagography . Computerized tomography showed a small, round foreign body in the middle of the cyst that was subsequently found to be a bingo chip . Communication between the cyst and the esophagus was not obvious at the time of surgery and had not been demonstrated by barium esophagography . When complete excision of the cyst is not possible because of inflammatory reaction all the mucosa must be removed to prevent recurrence . Careful postoperative respiratory support and broad-spectrum antibiotic therapy are recommended. Somat Cell Mol Genet, 1985 Mar, 11(2), 109 - 15 Amphotericin B enhances efficiency of DNA-mediated gene transfer in mammalian cells; Hidaka K et al.; Using plasmids containing the genes for thymidine kinase (tk) and neomycin resistance (neo), we have shown that DNA-mediated genotypic transformation of L and Chinese hamster ovary (CHO) cells is increased several-fold by the presence of the sterol-binding polyene antibiotic, amphotericin . Transformation into the same host cells, using genomic DNA, was also enhanced by amphotericin . Phenotypic expression of beta-galactosidase activity of a plasmid containing the gene for the enzyme was also markedly elevated when the antibiotic was added at transfection . Other sterol-binding polyene antibiotics also showed activity in these DNA-mediated gene transfer assays. Rev Infect Dis, 1985 Mar-Apr, 7(2), 244 - 56 Typhoid fever complicated by intestinal perforation: a persisting fatal disease requiring surgical management; Butler T et al.; In Bangladesh, clinical records of 323 patients with typhoid fever were reviewed to study the incidence, fatality, and optimal therapy of the complication of intestinal perforation . Fifteen patients (4.6%) developed intestinal perforation . Case-fatality rates were six of nine patients treated medically and one of four patients treated surgically for whom the postoperative courses were known . A literature review of 57,864 cases of typhoid fever in developing countries in the antibiotic era revealed that perforation developed in 2.5% of patients, a percentage that was similar to the incidence of 2.8% reported in the preantibiotic era . The median of case-fatality rates in these reports was 43% and the proportion of all reported typhoid deaths attributable to perforation was 25% . The case-fatality rates for patients with perforation were 70% for 410 patients managed medically and 26% for 1,835 patients managed surgically . Although some reports were biased toward placing patients at lower risk into surgical treatment, the large number of patients treated successfully by surgery suggests real improvement in surgical techniques in countries with endemic typhoid fever . These results indicate that intestinal perforation persists as a major cause of death in cases of typhoid fever in developing countries in the antibiotic era and that surgical treatment with use of antibiotic therapy is optimal for this complication. Rev Infect Dis, 1985 Mar-Apr, 7(2), 232 - 43 Therapeutic role of granulocyte transfusions; DiNubile MJ; Granulocyte transfusions are used as adjuvant therapy for infection in neutropenic patients with underlying neoplastic disease, neutropenic infants, and patients with qualitative white blood cell disorders . In addition, prophylactic leukocyte transfusions have been administered to patients during remission induction for acute leukemia or after bone marrow transplantation . The role of granulocyte therapy will need constant reassessment as new antibiotics and other forms of treatment are developed . At present, granulocyte transfusions are indicated in the treatment of severely neutropenic patients with documented bacterial infection who are unlikely to recover hematopoietic function over the next week and are deteriorating despite 48-72 hr of optimal antibiotic therapy . Under these conditions, they improve the rate of survival from the infectious episode without clearly affecting the longer-term survival of the patient . Only a small minority of neutropenic patients will require granulocyte transfusions. Radiat Res, 1985 Mar, 101(3), 508 - 18 Hepatic injury after whole-liver irradiation in the rat; Geraci JP et al.; Radiation-induced hepatic injury in rats, which is characterized by marked ascites accompanied by liver necrosis, fibrosis, and vein lesions, is described in this study . These adverse sequelae are produced within 30 days after irradiation if there is surgical removal of two-thirds of the liver immediately after whole-liver irradiation . The LD50/30 day and median survival time after liver irradiation and two-thirds partial hepatectomy is 24 Gy and 17 days, respectively . Death is preceded by reduction in liver function as measured by {131I}-labeled rose bengal clearance . Prior to death, liver sepsis and endotoxemia were detected in most irradiated, partially hepatectomized animals . Pretreatment of the animals with endotoxin and/or antibiotic decontamination of the GI tract, which increase the host resistance to infection and endotoxemia, resulted in increased survival time, but no irradiated, partially hepatectomized animal survived beyond 63 days . The combination of these treatments resulted in additive effects leading to 38% survival at 100 days . These treatments did not, however, prevent the eventual development of radiation-induced liver pathology . This suggests that sepsis and endotoxemia resulting from the bacteria in the intestine are the immediate cause of death after 30-Gy liver irradiation and partial hepatectomy . It is concluded that the hepatectomized rat model is an economical and scientifically manageable experimental system to study a form of radiation hepatitis that occurs in compromised human livers. J Bone Joint Surg Br, 1985 Mar, 67(2), 282 - 5 Excision of the clavicle . A review of the nineteenth-century literature; de Belder KR; Reports of excision of the clavicle in the nineteenth century literature are reviewed, and certain operative complications discussed . Osteomyelitis was the most common indication, and was described first in this country by Syme in 1833 . The first successful excision of the entire clavicle was performed by McCreary of Kentucky in 1813 . The removal of tumour-bearing clavicles provided memorable challenges at a time when anaesthetics were not available, blood transfusion unknown and antibiotic therapy non-existent. J Nucl Med, 1985 Mar, 26(3), 225 - 9 Indium-111 chloride imaging in chronic osteomyelitis; Sayle BA et al.; Sixty-eight patients with clinically suspected chronic osteomyelitis were studied with {111In}chloride . Fifty-four images were categorized as true positive; seven were categorized as true negative . There were four false-positive studies, two of which were associated with healing cancellous bone grafts . There were three false-negative studies in patients previously treated with long-term antibiotic therapy . Images in eight noninfected healing fractures 3 to 8 mo old were normal . Three patients with infected total hip prostheses had positive images . Two patients with loose prostheses had negative images . This study shows that {111In}chloride imaging is an accurate way to localize chronic osteomyelitis and may overcome some of the disadvantages of {67Ga}citrate such as localization in noninfected healing fractures and in some loose {67Ga}citrate such as localization in noninfected healing fractures and in some loose prostheses. Yale J Biol Med, 1985 Mar-Apr, 58(2), 179 - 87 Effect of protein synthesis inhibitors on leukocytic pyrogen-induced in vitro hypothalamic prostaglandin production; Bernheim HA et al.; In order to study the antipyretic effect of inhibitors of protein synthesis, hypothalamic tissue was incubated in vitro under controlled conditions and the amount of prostaglandin E2 (PGE2) measured in the supernatant medium . Rabbit anterior hypothalamic tissue was incubated with purified human leukocytic pyrogen (LP) and after 60 minutes the supernatant fluid was assayed for PGE2 by radioimmunoassay . Control tissue incubated with Eagle's medium (MEM) released elevated levels of PGE2; however, the addition of polymyxin B (PmxB), a cationic antibiotic which blocks the activities of bacterial endotoxins, significantly reduced PGE2 . In addition, endotoxin added to MEM induced from the brain tissue PGE2 production which could be reduced by the addition of PmxB . Thus, commercial culture media such as MEM may contain sufficient amounts of endotoxin to stimulate brain PGE2 production in vitro . Purified human LP incubated with hypothalamic tissue in the presence of PmxB induced PGE2 production in a dose-dependent fashion . This release could be reduced (p less than 0.001) by the presence of either cycloheximide or puromycin during incubation with LP . The addition of these inhibitors to unstimulated hypothalamic tissue incubations did not reduce background levels of PGE2 . It is concluded that the antipyretic effect of protein synthesis inhibitors results in a specific decrease in LP-induced levels of PGE2. Clin Chest Med, 1985 Mar, 6(1), 55 - 62 Parapneumonic effusions and empyema; Light RW; Nearly 50 per cent of patients with acute bacterial pneumonia have an accompanying pleural effusion (parapneumonic effusion) . With appropriate antibiotic therapy, the pleural effusion will resolve along with the pneumonia in the majority of patients . However, in a small fraction, the pleural effusion will not resolve unless drainage of the pleural space is instituted . Such patients are said to have complicated parapneumonic effusions . It is important to identify patients with complicated parapneumonic effusions as early as possible, since tube drainage of the pleural space becomes increasingly difficult the longer its institution is delayed . The possibility of a complicated parapneumonic effusion should be considered in every patient with bacterial pneumonia . If both diaphragms cannot be distinctly identified throughout their length on the lateral chest radiograph, decubitus chest radiographs should be obtained . If the thickness of the fluid on the decubitus radiograph is greater than 10 mm, a diagnostic thoracentesis should be performed . Only pleural fluid analysis can identify patients with complicated parapneumonic effusions . Complicated parapneumonic effusions are characterized by low pleural fluid pH and glucose levels, a high pleural fluid LDH, and a positive Gram stain of the pleural fluid . Tube thoracostomy should be performed immediately in a patient with an acute bacterial pneumonia if the pleural fluid glucose is below 40 mg per 100 ml, the pleural fluid pH is below 7.00, or if the Gram stain of the pleural fluid is positive . Patients with pleural fluid pH above 7.20, pleural fluid LDH below 1000 IU per L, and pleural fluid glucose levels above 40 mg per 100 ml respond well to only the administration of appropriate antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS) J Androl, 1985 Mar-Apr, 6(2), 127 - 35 Effects of white blood cells on the in vitro penetration of zona-free hamster eggs by human spermatozoa; Maruyama DK Jr et al.; The presence of white blood cells in semen has been associated with male infertility . Previous studies indicate that pyospermia occurs in conjunction with decreases in sperm motility, number of normal sperm forms, and penetration rates in the zona-free hamster egg sperm penetration assay . We have evaluated the relationship of seminal white blood cells and sperm function, as reflected in the zona-free hamster egg penetration assay, and have investigated the possible mode of action of the white cells . Egg penetration rates decreased when white blood cells from fertile or potentially fertile donors were added to their sperm suspensions prior to preincubation and at insemination in the in vitro assay . Zona-free hamster egg penetration assay results were also inhibited when the supernatant from white blood cells incubated in Biggers, Whitten, and Whittingham (BWW) medium overnight were introduced to sperm-oocyte suspensions at insemination . Conversely, egg penetration rates were enhanced in samples from hypofertile individuals when white blood cell concentrations in the semen or WBC/sperm ratios were reduced, either by physical removal or as a result of antibiotic therapy . The physical presence of leukocytes, and possibly, the extracellular release of lysosomal enzymes may be responsible for the inhibitory effects in vitro . Although the mechanism(s) by which white blood cells interfere with the fertilizing capacity of spermatozoa are not clear, it is quite obvious that their presence in the in vitro environment is undesirable and can mask an individual's actual fertilizing potential. Antibiot Med Biotekhnol, 1985 Mar, 30(3), 197 - 200 {Tetracycline sorption by alveolar macrophages of rabbits at early stages of interaction}; Kivman GIa et al.; Interaction of rabbit alveolar macrophages with morphocycline, tetracycline and methacycline was studied . The use of the membrane microfiltration technique in investigation of the antibiotic absorption by the macrophages provided description of the time course of the drug interaction with the cells at its early stages . It was shown that the macrophages mainly absorbed the tetracyclines within the first 20 seconds (1 minute incubation) . Later, within the period of 1-5 minutes no significant time course was observed . The medium temperature within 4-37 degrees C and the number of the cells in the system (0.1-5 minutes no significant time course was observed . The medium temperature within 4-37 degrees C and the number of the cells in the system (0.5-1 million/ml) had no effect on the parameters of the tetracyclines sorption by the macrophages . The percentage of the decrease of the morphocycline level in the extracellular medium was stable at the drug concentration in the cells ranging within 10-50 micrograms/ml . The respective figures for tetracycline and methacycline were 10-100 and 10-5000 micrograms/ml . Further increasing of the concentration of the antibiotics in the incubation medium resulted in a significant lowering of the percentage of their binding . It was suggested that absorption of the tetracyclines by the cells was associated with their intracellular binding. Afr J Med Med Sci, 1985 Mar-Jun, 14(1-2), 31 - 5 Clinical trial of cefoxitin (mefoxin) in parenteral therapy of septicemia (postabortal and postpartum) in Ibadan; Adelusi B et al.; Cases of post-abortal sepsis are admitted every day into the University College Hospital (UCH), Ibadan, Nigeria . This derives from the high incidence of induced (illegal) abortions in this environment . The infections are usually caused by mixed bacterial flora, often resistant to the common antibiotics because of the indiscriminate use of these drugs . Any new drug that can be effective in the treatment of these resistant cases will be welcome . The efficacy of Cefoxitin in the treatment of twenty-five cases of postabortal sepsis was therefore compared with the efficiency of other antibiotics in the management of sixty other cases . Response to Cefoxitin was prompt . Temperatures settled within 96 h and no case of pelvic abscess resulted . It was concluded that Cefoxitin could well be a safe and effective alternative antibiotic to replace the common antibiotics to which many hospital organisms have developed resistance. Proc Natl Acad Sci U S A, 1985 Mar, 82(5), 1376 - 80 The molecular origin of DNA-drug specificity in netropsin and distamycin; Kopka ML et al.; X-ray analysis of the complex of netropsin with the B-DNA dodecamer of sequence C-G-C-G-A-A-T-T-BrC-G-C-G reveals that the antitumor antibiotic binds within the minor groove by displacing the water molecules of the spine of hydration . Netropsin amide NH furnish hydrogen bonds to bridge DNA adenine N-3 and thymine O-2 atoms occurring on adjacent base pairs and opposite helix strands, exactly as with the spine of hydration . The narrowness of the groove forces the netropsin molecule to sit symmetrically in the center, with its two pyrrole rings slightly non-coplanar so that each ring is parallel to the walls of its respective region of the groove . Drug binding neither unwinds nor elongates the double helix, but it does force open the minor groove by 0.5-2.0 A, and it bends back the helix axis by 8 degrees across the region of attachment . The netropsin molecule has an intrinsic twist that favors insertion into the minor groove of B-DNA, and it is given a small additional twist upon binding . The base specificity that makes netropsin bind preferentially to runs of four or more A X T base pairs is provided not by hydrogen bonding but by close van der Waals contacts between adenine C-2 hydrogens and CH groups on the pyrrole rings of the drug molecule . Substitution of one or more pyrroles by imidazole could permit recognition of G X C base pairs as well, and it could lead to a class of synthetic "lexitropsins," capable of reading any desired short sequence of DNA base pairs. J Hosp Infect, 1985 Mar, 6 Suppl A, 123 - 5 The intra-operative application of povidone-iodine in neurosurgery; Strohecker J et al.; Over a period of 6 months 250 patients were operated on for lumbar disc prolapse, 125 patients each receiving prophylactic antibiotic therapy or only local, intra-operative administration of povidone-iodine . The analysis of variance showed a significant difference between the patient group treated with the antiseptic and the prophylactic antibiotic group . More abscesses and signs of infection occurred in the antibiotic treated group . Animal studies are also described. Biofizika, 1985 Mar-Apr, 30(2), 281 - 4 {Effect of amphotericin B added to one side of a membrane}; Kasumov KhM et al.; Amphotericin B which was added to the one side of a membrane in aqueous solutions with low pH 3.0 sharply increases the membrane conductance by the mechanism of channel forming . Long living ionic channels (20 sec) with large conductance dispersion (2-20 Ps) were found at the concentration 2 X 10(-8) M . Amphotericin B concentration which is necessary for obtaining single channels does not depend on cholesterol concentration in the membrane-forming solution in the range from 2 to 10 mg/ml . The effect of amphotericin B on the membrane depends on the phospholipid concentration in the membrane . The one-side selective permeability is the same as one under the symmetric action of the antibiotic . It is assumed that amphotericin B induced the membrane conductance by the mechanism of half-pores formation. Schweiz Med Wochenschr, 1985 Feb 23, 115(8), 261 - 6 {Prevalence of infectious diseases at the Vaud University Hospital Center}; Moreillon P et al.; The prevalence of infectious diseases at our hospital (Centre hospitalier universitaire vaudois, Lausanne {CHUV}, 900 beds) was studied retrospectively over a two years period (1980-1981) . The medical diagnosis of 30203 patients recorded in the computerized medical archives, representing 93% of the patients admitted during the period of observation, was reviewed . To assess the reliability of the computerized data, quality control was carried out through detailed analysis of all the histologically proven appendicitis recorded during 1981 . 88% of the histologically proven appendicitis were registered in the computer and the diagnosis was specific in 87% of cases . An infectious disease was the primary reason for admission in 12.8% of the patients (3873) during the study period . Altogether, 20.2% of patients presented with an infection during their hospital stay . Because of the retrospective nature of the study it was not possible to determine whether these additional infections were nosocomially acquired . The organ systems most frequently infected were the respiratory tract (28.5% of all infections), the digestive tract (20.5%), the skin and osteoarticular system (16%) and the urogenital tract (11.6%) . An infection was the primary reason for admission of 40.2% of the patients hospitalized in the dermatology service, of 19.7% of patients admitted in internal medicine, of 15-17% of the patients admitted in pediatrics, ENT and general surgery, and of 1-2% of the patients admitted in neurosurgery and radiotherapy . These observations highlight the continuing importance of infectious diseases in a modern hospital, in spite of high socio-economic levels, stringent hygiene and epidemiologic measures, and modern antibiotic availability. Presse Med, 1985 Feb 16, 14(7), 413 - 7 {Complications of mitral valve prolapse}; Bensaid J; Mitral valve prolapse, usually a benign condition, is aggravated in 15% of the cases by one or the other of five different complications . Mitral regurgitation may develop progressively or abruptly following rupture of the chordae tendinae and requiring prompt surgical repair . Bacterial endocarditis has been observed in 2.9% of the cases, hence the need for preventive antibiotic therapy prior to dental treatments or surgical operations in patients with holosystolic or end-systolic mitral murmur . Among arrhythmias, only ventricular extrasystoles (which are frequent and most often occur in pairs or salvos or are polymorphous) tachycardia and ventricular fibrillation may be considered as true complications of mitral valve prolapse and should be treated initially with beta-blockers . Sudden death is the major complication encountered in 1.4 to 2.4% of the patients; particularly exposed are women around 40 years of age who previously experienced syncopes or episodes of faintness due to attacks of tachycardia or ventricular fibrillation . Ophthalmic or cerebral ischaemic accidents occur with an incidence of 3.5%; some 20 to 30% of subjects under 45 who suffer from these accidents present with mitral valve prolapse. J Am Vet Med Assoc, 1985 Feb 15, 186(4), 393 - 4 Gastric zygomycosis (mucormycosis) in 4 suckling pigs; Sanford SE; Acute gastric zygomycosis (mucormycosis) was diagnosed in four 6- to 7-day-old pigs with large venous infarcts in the gastric fundus . Two pigs were from one farm where several dams had developed fever at parturition and most of their litters had died . The other 2 pigs, from separate farms, had diarrhea that was unresponsive to broad-spectrum antibiotic therapy . Histologically there was severe hemorrhagic, ulcerative gastritis associated with numerous transmurally invading, mucoraceous fungi . The discussion includes speculation on the pathogenesis of this lesion in neonatal pigs. Clin Chim Acta, 1985 Feb 15, 145(3), 267 - 73 Copper and iron complexes catalytic for oxygen radical reactions in sweat from human athletes; Gutteridge JM et al.; Sweat collected from 'explosive' and 'endurance' athletes immediately after exercise contains low molecular mass complexes of copper detectable by their ability to bind to o-phenanthroline . Concentrations of these copper complexes are much greater in arm sweat than in trunk sweat . The iron content of arm sweat, as determined by the ferrozine method, is also greater than that of trunk sweat . However, much of the iron in trunk sweat exists in a low molecular mass form that can bind to the antibiotic bleomycin, whereas the iron in arm sweat does not exist in this form . The metal complexes in human sweat are capable of stimulating the peroxidation of membrane lipids in the presence of ascorbic acid . The physiological significance of the presence of iron and copper complexes in sweat is discussed. J Biol Chem, 1985 Feb 10, 260(3), 1618 - 22 The role of intramembrane Ca2+ in the hydrolysis of the phospholipids of Escherichia coli by Ca2+-dependent phospholipases; Elsbach P et al.; Ca2+-dependent phospholipases A require Ca2+ concentrations in the millimolar range for optimal activity toward artificial substrates . Because Ca2+-dependent phospholipases A2 degrade the phospholipids of Escherichia coli, treated with the membrane-active antibiotic polymixin B equally well with and without added Ca2+ (Weiss, J., Beckerdite-Quagliata, S., and Elsbach, P . (1979) J . Biol . Chem . 254, 11010-11014), we have examined the possibility that intramembrane Ca2+ can provide the Ca2+ needed for phospholipase action . We studied the effect of Ca2+ depletion on the hydrolysis of the phospholipids of polymixin B-killed E . coli by 1) added pig pancreas phospholipase A2 in E . coli S17 (a phospholipase A-lacking mutant) and 2) endogenous Ca2+-dependent phospholipase A1 in the parent strain E . coli S15 . Transfer of E . coli from nutrient broth (Ca2+ concentration approximately 3 X 10(-5) M) to Ca2+-depleted medium (Ca2+ concentration less than 10(-6)M) reduced polymixin B-induced hydrolysis by 50-75%, in parallel with a reduction of bacterial Ca2+ from 19.6 +/- 2.8 to 3.9 +/- 0.6 nmol (mean +/- standard error) per 3 X 10(10) bacteria . The bacterial Ca2+ content was repleted and the sensitivity of the bacterial phospholipids to hydrolysis by both exogenous phospholipase A2 (E . coli S17) and endogenous phospholipase A (E . coli S15) was restored by adding Ca2+ back to the suspensions . Complete restoration occurred at low Ca2+ levels in the reaction mixture (3 X 10(-5) - 10(-4) M) and required time, suggesting that hydrolysis was restored because bacterial Ca2+ stores were gradually replenished and not because extracellular Ca2+ concentrations were raised to levels that were still at least 10X lower than needed for optimal phospholipase A activity . This conclusion is supported by the finding that Ca2+ depletion or addition caused respectively decreased and increased release of lipopolysaccharides by EGTA (ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid), suggesting that the bacterial Ca2+ pool bound to lipopolysaccharides in the outer membrane shrinks or expands depending on extracellular Ca2+ levels . Thus, the cationic membrane-disruptive polymixin B, thought to compete with Mg2+ and Ca2+ for the same anionic sites on lipopolysaccharides, may liberate the Ca2+ near where the phospholipids are exposed to phospholipase. Hinyokika Kiyo, 1985 Feb, 31(2), 289 - 94 {Emphysematous pyelonephritis: report of a case}; Takigawa H et al.; A case of emphysematous pyelonephritis is presented . A 54-year-old woman with diabetes mellitus was admitted because of bilateral ureteral stones . Five days after bilateral ureterolithotomy, she developed left flank pain, chills and fever . Plain x-rays of the abdomen (KUB) showed an enlarged left kidney with a giant gas shadow on the left renal area and no evidence of stone shadow . Drip infusion pyelogram revealed a decrease in the left renal function and the presence of the gas in the pyelocalyceal system . Contrast-enhanced computerized tomograms confirmed the presence of the gas in the parenchyma and pyelocalyceal system . The patient was treated conservatively with intensive antibiotic therapy, intravenous fluids and control of diabetes mellitus . After 3 weeks of therapy, the gas shadow disappeared, and a good recovery of renal architecture and function was achieved. Jpn J Antibiot, 1985 Feb, 38(2), 230 - 4 {Study on the transfer of cefroxadine to human tears}; Hara J et al.; A comparative study to determine the transfer of cefroxadine (CXD), an oral cephem antibiotic, to the human tears was undertaken using cephalexin (CEX) as the control drug . The mean tear levels of 250 mg each of CXD and CEX after oral administration in 6 volunteers were equally peaked at 0.26 micrograms/ml with CXD after 1 to 2 hours and with CEX after 2 hours . The changes of tear levels were also equal for both drugs . The ratios between the tear and the blood levels at 2 hours after oral administration were almost equal with 4.1% for CXD and 3.7% for CEX . From the above evidence it has been confirmed that the both drugs were equivalent with regard to the concentration profiles in human tears after oral medication. Arch Fr Pediatr, 1985 Feb, 42(2), 129 - 32 {Factors of meningeal diffusion of amoxicillin and ampicillin at the acute phase of purulent meningitis in children}; Coquerel A et al.; Amoxicillin and ampicillin levels were comparatively studied in blood and CSF of children with purulent meningitis . Thirty one children aged 2 months to 11 years were treated by one of two beta lactams by monotherapy in a daily dose of 200 mg/kg (Group 1: amoxicillin, n = 17; group 2: ampicillin, n = 14) . Samples were collected on day 2 one hour after administration of 50 mg/kg IV of the chosen antibiotic . The mean levels observed in serum (69.5 and 53.4 micrograms/ml) and in CSF (7.74 and 7.96) were not significantly different . Beyond these levels we studied different biologic parameters in CSF: leucocytes, polymorphonuclears, protein, glucose and lactic acid . Multiple linear correlations were found, for the two groups and for the whole population between the CSF antibiotic level and the 6 other parameters (group 1: R1 = 0.82; group 2: R2 = 0.88; group 1 + 2: R3 = 0.78) . The best correlated parameters with antibiotic CSF level are serum antibiotic level and CSF lactic acid . With these two parameters we can also estimate antibiotic level in CSF with good correlations (R1 = 0.78; R2 = 0.72 and R3 = 0.72). Antibiot Med Biotekhnol, 1985 Feb, 30(2), 90 - 6 {Mechanism of daunorubicin interaction with DNA}; Brikenshtein VKh et al.; The kinetics of binding of rubomycin and its aglycon (daunomycinon) with DNA was studied with the stopped flow method . It was shown that the reaction of formation of the complex of daunorubicin with DNA involved two stages . At the first stage the antibiotic aglycon intercalated between the pairs of DNA bases and at the second stage the resulting complex was additionally stabilized due to interaction of the positively charged amino sugar residue of the antibiotic with the negatively charged DNA phosphates . The reaction of formation of the complex of daunomycinon with DNA involved one stage . Estimation of the constants characterizing the above reactions is presented. Antibiot Med Biotekhnol, 1985 Feb, 30(2), 128 - 31 {Various indicators of amphotericin B pharmacokinetics in infants with Candida meningitis during the 1st year of life}; Rainer MA; The incidence of candidiasis meningitis in infants has lately increased . This required choosing of the dose and regimen for the use of amphotericin B, the only drug effective in the treatment of generalized mycoses . The antibiotic levels in the blood and CSF were determined in 14 infants at various periods after discontinuation of intravenous drip infusion of amphotericin B . It was shown that the therapeutic concentrations of the antibiotic in the blood were attained when it was administered in a dose of 120-200 units/kg twice a day . For attaining the therapeutic concentrations of the antibiotic in the CSF, daily endolumbar administration of amphotericin B in a dose more than 10 units in addition to its intravenous drip infusions was required . Therefore, the tactics of amphotericin B use in the treatment of candidiasis meningitis in infants was developed. J Antibiot (Tokyo), 1985 Feb, 38(2), 230 - 5 Studies on antineoplastic activity of naphthomycin, a naphthalenic ansamycin, and its mode of action; Okabe T et al.; An antibiotic, identical with naphthomycin, was isolated from a soil Streptomyces . The antibiotic displayed significant therapeutic activity by ip administration against murine tumors: Ehrlich carcinoma and IMC carcinoma implanted ip . The maximum increase of life-span was more than 169% in Ehrlich carcinoma, and 128% in IMC carcinoma . The antibiotic exhibited a potent cytotoxicity against murine leukemic cells: P388, L1210, and L5178Y . IC50 was 0.4-1.3 microgram/ml in culture . The activity of naphthomycin was reversed by SH compounds: 2-mercaptoethanol, dithiothreitol, and glutathione . DNA and RNA syntheses were more markedly inhibited by naphthomycin than protein synthesis in L5178Y cells . Approximately 50% inhibition of nucleic acid syntheses was observed at an antibiotic concentration of 2 micrograms/ml . Naphthomycin blocked alkaline phosphodiesterase obtained from L5178Y cells: IC50 was ca . 7.6 micrograms/ml . The antibiotic neither caused metaphase arrest nor prevented tubulin polymerization . The results suggest that the mechanism of cytotoxicity of naphthomycin is the inhibition of various SH enzymes, particularly those involved in nucleic acid biosynthesis . The mode of action is unique in the ansamycin group of antibiotics. J Antibiot (Tokyo), 1985 Feb, 38(2), 181 - 5 Raman spectra of nystatin . Influence of impurities; Colline A et al.; The Raman spectra of the polyene antibiotic nystatin have been investigated between 1500 and 1650 cm-1 . Only one band is observed in the resonance Raman spectra obtained with a 3045 A excitation radiation . Two major bands are observed in the preresonance spectra of pure nystatin obtained with a 4545 A excitation . A supplementary band at 1557 cm-1 observed in the preresonance spectra of samples of commercial origin is ascribed to the presence of heptaene impurities, the Raman spectra of which are preferentially enhanced by resonance, owing to the closer proximity of their absorption to the excitation radiation. Paraplegia, 1985 Feb, 23(1), 47 - 55 Gentamicin disposition kinetics in humans with spinal cord injury; Segal JL et al.; The disposition kinetics of gentamicin, an aminoglycoside antibiotic, were studied in seven tetraplegic and six paraplegic volunteers . The volume of distribution of gentamicin in l/kg of body weight varied in a statistically significant way from values of this parameter measured in normal subjects . The elimination of gentamicin in spinal man proceeded in a log-linear fashion accurately characterized by a one compartment open-model with a half-life of approximately 2 hours . The clinical significance of altered disposition kinetics and an increased intersubject variability in gentamicin disposition in spinal man as compared to normal subjects is unknown . The existence of these observed differences in pharmacokinetic parameters, however, emphasizes the need to define individual pharmacokinetic profiles and individualize dosing regimens in spinal man . The data presented are supportive of the hypothesis that spinal man constitutes a discreet therapeutic population. Arch Intern Med, 1985 Feb, 145(2), 346 - 7 Esophageal carcinoma masquerading as recurrent acute suppurative thyroiditis; Walfish PG et al.; A 61-year-old woman had clinical features of acute suppurative thyroiditis that was recurrent and refractory to antibiotic therapy . The diagnosis of acute suppurative thyroiditis was established by a fine-needle aspiration biopsy procedure, yielding suppurative material from which anaerobic and aerobic bacteria grew . Subsequent investigation with a barium swallow study followed by esophagoscopy and biopsy confirmed extensive esophageal carcinoma with a fistulous tract extending into the perithyroidal region. Am J Hosp Pharm, 1985 Feb, 42(2), 332 - 5 Stability and cost analysis of clindamycin-gentamicin admixtures given every eight hours; Mansur JM et al.; Stability and costs of a mixture of clindamycin and gentamicin in a single carrier solution for every-eight-hour i.v . administration were analyzed . Duplicate solutions containing clindamycin 900 mg (as the phosphate salt) and gentamicin 100 mg (as the sulfate salt) in 5% dextrose injection 150 mL in flexible plastic containers were prepared . Samples withdrawn at 0-24 hours were visually inspected and assayed for content of both drugs . Clindamycin concentrations were determined by high-performance liquid chromatography and gentamicin concentrations by fluorescence-polarization immunoassay . Preparation and administration times were measured in two trials to determine cost differences between every-eight-hour administration of the two-antibiotic mixture and separate administration of the two drugs (four daily doses of clindamycin and three of gentamicin) . No precipitate was seen . Concentrations of both drugs after 24 hours were greater than 90% of initial concentrations . Total daily costs (per patient) for labor, drug, and carrier solution were $3.08 less when the two drugs were mixed and administered every eight hours . At the concentrations studied, clindamycin and gentamicin mixed together in 5% dextrose injection are stable for 24 hours . Administration of this drug mixture every eight hours is safe and less costly than separate administration of the two drugs. J Clin Microbiol, 1985 Feb, 21(2), 280 - 1 Lactic acid levels in pleural fluid from patients with bacterial pleuritis; Riley TV; Pleural fluid lactic acid estimations were carried out on 60 samples by gas-liquid chromatography . Lactic acid levels in 12 patients with bacterial pleural infection were statistically significantly higher (mean, 287 mg/dl; range, 135 to 482 mg/dl) than in 18 patients with malignancy (mean, 71 mg/dl; range, 24 to 157 mg/dl) and 30 other patients with pleural effusions (mean, 19 mg/dl; range, 10 to 57 mg/dl) . The determination of pleural fluid lactic acid may help in differentiating between empyema and nonbacterial pleural effusions in most cases . It is of particular value when antibiotic therapy has commenced before specimen collection and may be useful for monitoring therapy. Gan To Kagaku Ryoho, 1985 Feb, 12(2), 303 - 8 {A study on the correlation between the concentration of antitumor agent and the clinical effect . An experience with THP-ADM}; Ogawa A et al.; A new anthracycline antibiotic agent, THP-adriamycin (THP-ADM) was administered to patients with malignant head and neck tumors . Among them, intraarterially injected cases achieved excellent primary effects; 3 CR, 4 PR and 2 NC out of 9 cases . Patients received THP-ADM 10 mg/body every other day, to a total of 100 mg . In order to elucidate the factors responsible for this result, the concentration level of THP-ADM in plasma, blood cells and in tumor tissue was measured by high-performance liquid chromatography at various time intervals . Changes in concentration of THP-ADM were similar in both intraarterial and intravenous cases . Among these, the concentration levels in blood cells were always higher than in the plasma and were reduced rapidly with the passage of time; about hour 1 after administration, THP-ADM levels diminished considerably, especially in the plasma . On the other hand, in tumor tissue, the concentration level was exceedingly high at 1 hour after injection, and was still high-24 hours later . In intraarterial cases, these levels were about seventy times higher than in intravenous cases at 1 hour after injection . From these observations, the authors found a very good correlation between the tissue concentration level and the clinical effects obtained. Am J Med, 1985 Feb, 78(2), 235 - 40 Diagnosing early Lyme disease; Shrestha M et al.; The diagnostic value of clinical, culture, and serologic findings was studied prospectively in 41 patients with early Lyme disease . Fifteen patients had erythema chronicum migrans alone, and 26 had clinical evidence of disseminated infection, most commonly affecting the brain or meninges, other skin sites, lymph nodes, or joints . Of 40 blood cultures, only one, from a patient with disseminated infection, yielded spirochetes . One of 10 patients tested with localized infection had an elevated IgM response to the Lyme spirochete (200 units or greater) during acute disease . Two to three weeks after beginning antibiotic therapy, four of the 10 patients had elevated specific IgM or IgG responses (200 units or greater) . Of the 22 patients tested with disseminated disease, 10 initially had elevated levels of specific IgM or IgG, and 12 had such responses by convalescence . Because of the low yield of cultures and the delay in the specific antibody response, recognition of the clinical picture remains very important in diagnosing early Lyme disease. J Pediatr, 1985 Feb, 106(2), 305 - 10 Adverse drug reactions in general pediatric outpatients; Kramer MS et al.; We used a recently developed diagnostic adverse drug reaction (ADR) algorithm and an intensive telephone surveillance program to monitor all courses of prescription and nonprescription drug therapy in a general pediatric group practice for 1 year . A total of 3181 different children visited the practice during the year and received 4244 separate courses of drug therapy . Adverse symptoms were noted in 473 (11.1%) of these courses of therapy . Of 534 total adverse symptoms, however, only 24 scored as definite and 176 as probable ADRs . The main ADRs noted were antibiotic-associated gastrointestinal complaints and rashes, and various manifestations of CNS stimulation with bronchodilators . Sociodemographic variables significantly associated with the risk of a definite or probable ADR were socioeconomic status (P less than 0.0001), ethnic origin (P = 0.0015), and age (P less than 0.05) . Treatment-related risk factors included treatment by a practitioner outside the study practice (usually during nonoffice hours) (P less than 0.001) and administration of a dosage above the range recommended by the manufacturer (P less than 0.001) . Half the ADRs were judged as inconsequential by the children's parents, and most of the remainder resulted in only minor morbidity . Half were judged to be highly or probably preventable . Our results suggest that ADRs do not occur commonly in general pediatric outpatients and that most are mild and self-limited. Antibiot Med Biotekhnol, 1985 Feb, 30(2), 99 - 101 {Spectrophotometric method of determining phenoxymethylpenicillin in the air}; Churagulova NK; A modified spectrophotometric method is recommended for the control of the air condition at pharmaceutical plants manufacturing phenoxymethylpenicillin and its dosage forms . The method is based on measuring absorption of the mixture solutions at two (258 and 268) and three (253, 268 and 261) wave lengths . The limit of the measuring in the solution volume is 0.015 mg . The air samples are collected on filters AFA-VP-20 or AFA-KHP-20 at an aspiration rate of 15-20 l/min and then the antibiotic is extracted in a 0.04 per cent solution of sodium bicarbonate. Eur J Clin Invest, 1985 Feb, 15(1), 1 - 5 Stimulation of peritoneal synthesis of vasoactive prostaglandins during peritonitis in patients on continuous ambulatory peritoneal dialysis; Steinhauer HB et al.; The peritoneal generation of arachidonic acid metabolites was studied in eight patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD) during infection-free periods and during bacterial peritonitis . The prostacyclin metabolite 6-keto-PGF1 alpha was found to be the major prostanoid generated by human peritoneal mesothelium (1090 ng (6h)-1, SEM 86, n = 8) followed by lesser amounts of PGE2 (142 ng (6 h)-1, SEM 26, n = 8), PGF2 alpha (162 ng (6 h)-1, SEM 27, n = 8) and TXB2 (59 ng (6 h)-1, SEM 5, n = 8) . During peritonitis a significant increase of all prostaglandins and TXB2 occurred (P less than 0.001) . The ratio of the vasodilating prostaglandins and their metabolites (PGE2 and 6-keto-PGF1 alpha) to the vasoconstrictors and their metabolites (PGF2 alpha and TXB2) increased from 6.6 to 10.5 during peritoneal inflammation . Augmented peritoneal clearances of creatinin and urea and increased losses of proteins during peritonitis as well as the enhanced peritoneal generation of prostanoids were reduced to basal values by adequate antibiotic therapy . The present results suggest that the increased peritoneal blood flow during peritonitis, probably responsible for the observed changes of peritoneal transport properties, may be induced by a change in the ratio of vasoactive prostaglandins generated by peritoneal mesothelial cells. J Bacteriol, 1985 Feb, 161(2), 627 - 35 Correlation between degradation and ultrastructure of peptidoglycan during autolysis of Escherichia coli; Leduc M et al.; The kinetics of peptidoglycan degradation were examined under different conditions of autolysis of Escherichia coli . With cephaloridine- or moenomycin-induced autolysis, degradation did not exceed 25 to 35%, whereas in EDTA-induced autolysis it rapidly reached 65 to 70% . When nonautolyzing cells were fixed overnight with glutaraldehyde, followed by an osmium fixation, and thin sections were stained by the phosphotungstic acid method, a dark, 15-nm-thick layer of uniform appearance and constant width occupied the whole area between the inner and outer membranes of the envelope . The stained material was tentatively identified with peptidoglycan . Ultrastructural changes in this phosphotungstic acid-stained periplasmic space were investigated at different time intervals after induction of autolysis . In all cases, breakdown proceeded over the whole cell surface . During antibiotic-induced autolysis a progressive thinning down limited to the inner side of the layer was observed . During EDTA-induced autolysis, the rapid decrease in thickness correlated well with the important loss of material labeled with {3H}diaminopimelic acid . Considering these changes and the insufficient amounts of peptidoglycan (1.3 U/nm2) necessary to account for a regularly structured polymer occupying the whole 15-nm layer, it was speculated that peptidoglycan might be unevenly distributed throughout the periplasmic space. Emerg Med Clin North Am, 1985 Feb, 3(1), 143 - 60 Complications of bacterial infection of the ears, paranasal sinuses, and oropharynx in adults; Ramsey PG et al.; Early recognition of potentially fatal complications of bacterial infections of the ears, sinuses, and pharynx is important for successful therapy . The clinical presentations of these infections are reviewed in this article, and the approach to initial diagnostic tests is outlined . Treatment recommendations are briefly discussed, with emphasis placed on early antibiotic therapy and indications for consultations from surgical colleagues. Emerg Med Clin North Am, 1985 Feb, 3(1), 127 - 42 Infectious diarrhea; Kimmey M; Patients presenting to the emergency department with diarrhea should be evaluated for infectious causes . Information obtained from the history and physical examination should be used in deciding whether symptomatic treatment alone is sufficient or whether the patient's stool should be examined for pathogens . Antiperistaltic agents should be used only in selected patients, usually after the results of stool cultures are known to be negative . Antibiotic administration should be based on results of stool cultures and examination for parasites . Finally, the emergency physician should be familiar with the special situations of traveler's diarrhea, food-borne illness, and sexually transmitted enteric disease. Antibiot Med Biotekhnol, 1985 Feb, 30(2), 119 - 22 {Immunosuppressive properties of olivomycin}; Vatin OE; The effect of olivomycin on the cell and humoral immune response was studied on mice . It was shown that antibody genesis stimulated by sheep red blood cells or E . coli lipopolysaccharide was almost equally inhibited by olivomycin when administered 24 hours before administration of the antigen . The magnitude of the delayed type hypersensitivity induced by the antigen low doses (10(5) cells) did not change when the antibiotic was administered in a dose of 1.5 mg/kg . When the antibiotic dose was 3 mg/kg, it decreased 2 times as compared to the control . On immunization of the mice with sheep red blood cells in a dose of 10(9) cells olivomycin administered in the doses inhibiting the antibody genesis induced an increase in the delayed type hypersensitivity . Such an effect of the antibiotic has much in common with the effect of other cytostatics. Can J Microbiol, 1985 Feb, 31(2), 119 - 23 Effect of ammonium on chloramphenicol production by Streptomyces venezuelae in batch and continuous cultures; Shapiro S et al.; Cultures of Streptomyces venezuelae presented with a mixture of ammonium and an amino acid as nitrogen sources used both compounds together . Absence of ammonium repression of alternative nitrogen assimilation pathways was also observed when ammonium was added to cultures already growing on proline . The presence of ammonium in the medium ab initio depressed the yield of chloramphenicol . However, its addition to a culture growing on proline caused only a temporary inhibition of antibiotic synthesis, even when sufficient ammonium was added to create an excess . Continuous cultures supplied with ammonium as the growth-limiting nutrient showed no significant change in specific antibiotic production at different specific growth rates . The overall results indicate that in S . venezuelae neither nitrogen utilization pathways nor chloramphenicol biosynthesis is controlled by nitrogen repression. J Gen Microbiol, 1985 Feb, 131 ( Pt 2), 265 - 71 Inhibition of glucosamine synthase by bacilysin and anticapsin; Chmara H; L-Glutamine:D-fructose-6-phosphate amidotransferase ('glucosamine synthase', EC 5.3.1.19) from Escherichia coli MRE 600 was purified at least 75-fold . It catalysed the formation of 21.1 mumol glucosamine 6-phosphate (mg protein)-1 in 30 min at 37 degrees C . Its molecular weight, estimated by gel filtration, was about 90000 and it was inhibited by thiol group reagents . Anticapsin, the C-terminal amino acid of the dipeptide antibiotic bacilysin, and to a lesser extent bacilysin itself, inhibited glucosamine synthase activity . Kinetic studies indicated that the inhibition was non-competitive with respect to fructose 6-phosphate as substrate but partly competitive with respect to L-glutamine . Incubation of the enzyme with anticapsin brought about a time-dependent and irreversible inhibition . It is suggested that anticapsin behaves as a glutamine analogue and that a reaction of its epoxide group with a thiol group of glucosamine synthase results in its linkage to the enzyme by a covalent bond. J Antimicrob Chemother, 1985 Feb, 15(2), 239 - 45 Treatment of neutropenic infection: a randomized trial comparing latamoxef (moxalactam) with cephradine plus tobramycin; Bezwoda WR et al.; Sixty neutropenic patients with infection were studied in a randomized trial comparing treatment with latamoxef (moxalactam) alone or with cephradine and tobramycin . The two treatment groups were comparable in respect to their clinical sites of infection, degree of neutropenia underlying malignancy, and organisms . Forty-two bacterial isolates were obtained from various clinically infected sites . All but two of these isolates were sensitive to latamoxef (30 highly sensitive, ten moderately sensitive) . In contrast 29 of the isolates were resistant to cephradine and eight were resistant to both cephradine and tobramycin . Control of infection was achieved in 72% of patients treated with latamoxef and 55% treated with cephradine plus tobramycin . Latamoxef appears to be an effective antibiotic for the treatment of neutropenic patients with infection. Am J Physiol, 1985 Feb, 248(2 Pt 1), E194 - 202 Role of hepatocyte plasma membrane in insulin degradation; Blackard WG et al.; An important role of the cell membrane in insulin degradation by cultured rat hepatocytes is supported by studies using the surface-active antibiotic bacitracin . Bacitracin inhibited degradation of cell-associated insulin (both randomly and A14 labeled) by 80-90% at 15 degrees C and by 60% at 37 degrees C . At 37 degrees C, inhibition of degradation was observed only with bacitracin present during dissociation and was accompanied by a compensatory increase in release of trichloroacetic acid (TCA)-precipitable insulin . This profile suggests inhibition of insulin degradation on the membrane after either primary binding or diacytosis (endocytosis-reverse endocytosis) . In contrast, at 15 degrees C, bacitracin's inhibitory effect was greater with the antibiotic present during association and was not accompanied by a compensatory increase in TCA-precipitable insulin . This profile was compatible with inhibition of partial cleavage of insulin on the membrane . Internalization and degradation through chloroquine-sensitive pathways may be required to complete degradation at this temperature because chloroquine exhibited an inhibitory effect on insulin degradation equally potent to that of bacitracin at 15 degrees C (no effect at 37 degrees C). Urology, 1985 Feb, 25(2), 142 - 4 Renal carbuncle: comparison between surgical open drainage and closed percutaneous drainage; Fernandez JA et al.; This article represents a retrospective study of 12 patients with renal carbuncle treated at the combined urological services of The Mason Clinic in Seattle, Washington, and Madigan Army Medical Center in Tacoma, Washington . All patients were initially treated with antibiotics . Two recovered without further treatment . Of the 10 patients who failed to respond, 2 underwent nephrectomy for nonfunctioning kidneys, 4 underwent closed percutaneous drainage, and 4 underwent surgical open drainage . All patients treated with open surgical drainage recovered and retained functioning kidneys . Of the 4 patients who underwent closed percutaneous drainage, 2 failed to respond and required subsequent emergency nephrectomy because of sepsis . The authors believe that renal exploration and open drainage should be the initial definitive mode of surgical treatment of renal carbuncle in those patients who fail antibiotic therapy alone. Crit Care Med, 1985 Feb, 13(2), 102 - 4 Continuous arteriovenous hemofiltration as an adjunctive therapy for septic shock; Ossenkoppele GJ et al.; The effects of continuous arteriovenous hemofiltration were studied in septic patients with acute renal failure and gross fluid overload . Hemofiltration was performed for a mean of 7 days per patient (range 1 to 14 days) . The mean filtration volume was 3.64 L/day . The mean total ultrafiltration volume per patient was 25.5 L . The patients were hemodynamically stable during hemofiltration, as indicated by measurements of arterial blood pressure, CVP, pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac output . Multiple simultaneous measurements in both serum and ultrafiltrate showed a very close correlation for sodium, potassium, phosphorus, urea and creatinine levels . There was no detectable protein in the ultrafiltrate . The calcium concentration in the ultrafiltrate was relatively low . Finally, antibiotic levels in the ultrafiltrate were almost equal to serum levels . There were no significant complications; in this series of patients hemofiltration was a safe and effective treatment of fluid overload. Biochem J, 1985 Feb 1, 225(3), 829 - 32 Design of a new DNA-polyintercalating drug, a bisacridinyl peptidic analogue of Triostin A; Helbecque N et al.; The synthesis of a new bifunctional compound in which two aminoacridine chromophores are linked by the bicyclic depsipeptidic backbone of des-N-tetramethylTriostin A is described . The molecule, bis-{(9-acridinyl)-D-seryl-L-alanyl-L-cysteinyl-L-valine} dilactone disulphide, structurally analogous to the antibiotic anti-tumour drug Triostin A, is shown to possess a high affinity to DNA and to act as a bis-intercalator on the basis of spectroscopic, viscosimetric and thermal-denaturation studies . This model constitutes the first attempt of a synergic association between a peptidic moiety that mimics a naturally occurring drug and aminoacridine, the two parts themselves each exhibiting a high affinity for the DNA target. Methods Find Exp Clin Pharmacol, 1985 Feb, 7(2), 87 - 91 Effect of diabetogenic action of streptozotocin on rat serum lipoproteins; Brunet C et al.; After studying the diabetogenic action of streptozotocin in rats on adipose tissue cellularity, the authors attempted to demonstrate the influence of streptozotocin on cholesterol and phospholipid composition of the different serum lipoproteins . Intravenous injection of that antibiotic induced in rats a diabetes which appears at the latest on about the third day and finally remains at a fixed value at about the second week . All very low density lipoproteins (VLDL) are increased, which is not surprising since diabetes induces a hypertriglyceridemia and VLDL are triglyceride carriers . On the other hand, high density lipoproteins (HDL) are decreased, so that we can ask the question: Is HDL decrease due to diabetes or as a result of hypertriglyceridemia? Mol Cell Biol, 1985 Feb, 5(2), 410 - 3 A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus; Sugden B et al.; Epstein-Barr virus (EBV) transforms human B-lymphocytes into proliferating blasts which are efficiently established into cell lines . The viral DNA in these cell lines is usually present as complete, unintegrated plasmid molecules . A cis-acting element of EBV, oriP, permits plasmid maintenance in adherent cells that carry EBV DNA . We constructed a vector, pHEBo, that carries oriP and showed that it is also efficiently maintained as a plasmid when introduced into EBV-transformed B-lymphoblasts . The pHEBo vector carries the coding sequences for the hph gene from Escherichia coli such that it can be expressed in mammalian cells and confers resistance to the antibiotic hygromycin B . Hygromycin B kills EBV-transformed lymphoblasts at concentrations of 50 to 300 micrograms/ml . The combination of oriP plus the expressed hph gene makes pHEBo useful for the stable introduction of genes on plasmids into EBV-transformed lymphoblasts . Because pHEBo is derived from the plasmid pBR322 it can be easily isolated from lymphoblasts by reintroduction into E . coli. Dig Dis Sci, 1985 Feb, 30(2), 143 - 8 Studies on lymphocyte subpopulations in human colonic biopsy specimens by colonoscopy; Miyazaki H et al.; Lymphocytes, isolated by the enzymatic technique, from colonic mucosal specimens obtained from eight patients with ulcerative colitis (UC), two with ischemic colitis, two with antibiotic-associated colitis, and 15 controls by colonoscopic biopsy were used to examine T and B cells . In control biopsy specimens, the mononuclear cell yield averaged 3.6 +/- 0.3 (SEM) X 10(6)/g with a viability of 93 +/- 1%, while T and B cells expressed as a percentage of total lymphocyte counts were 65 +/- 1% and 15 +/- 1%, respectively . T and B cells in the ascending, transverse, and sigmoid colon and rectum did not present any differences . In involved tissue at the active stage of UC, the mononuclear cell yield averaged 11.4 +/- 2.1 X 10(6)/g, and T and B cells constituted 49 +/- 3% and 43 +/- 4%, respectively . After treatment for two months with salazosulfapyridine, mononuclear cell yields in five cases of UC were significantly reduced to an average of 3.9 +/- 0.8 X 10(6)/g as compared to the pretreatment level (P less than 0.01) . The percentage of T cells was significantly increased from 48 +/- 2% to 62 +/- 2% (P less than 0.01), and that of B cells was significantly reduced from 39 +/- 2% to 27 +/- 3% (P less than 0.01) . These results revealed a significant difference in the subpopulations of mucosal lymphocytes in the involved sites in the active stage of UC as compared to normal controls, suggesting that immunological abnormalities may be implicated in the etiology of this disease and that disease remission on salazosulfapyridine treatment is associated with a correction of the colonic lymphocyte abnormalities. J Physiol, 1985 Feb, 359, 189 - 217 Mechano-electrical transduction currents in isolated vestibular hair cells of the chick; Ohmori H; Properties of a mechano-electrical transduction channel were studied in enzymatically dissociated chick vestibular hair cells by using a whole-cell recording variation of the patch voltage-clamp technique . The apical hair bundle was stimulated by a glass rod which moved along a one-dimensional axis when stimulated by either a triangular or a trapezoidal command voltage . The motion of the glass rod was monitored optically using a photodiode . In response to triangular stimuli, the hair cell generated a current of triangular wave form with occasional step-like spiky or zigzag-appearing events . Control experiments confirmed that the current was generated only when the hair bundle was displaced towards the tallest stereocilium . The mechano-sensitive current was blocked by streptomycin and by neomycin . The blockage by streptomycin was clearly voltage dependent: the reduction of the current became larger with hyperpolarization of the membrane . This suggests that the positively charged antibiotic molecules plug the mechanically gated channels . From the evidence presented in 3 and 4 above, the mechano-sensitive current recorded here was identified as the mechano-electrical transduction (m-e.t.) current . The permeability of the m-e.t . channel to various monovalent cations was determined from reversal potential measurements . Since a CsCl-EGTA intracellular medium was used, all the permeabilities were calculated relative to PCs . The sequence of permeabilities was Li greater than Na greater than or equal to K greater than or equal to Rb greater than Cs greater than choline greater than TMA greater than TEA . External Ca ions were indispensable for the recording of transduction current and Sr ions could replace Ca ions without loss of the transduction activity . The minimum {Ca}o for stable generation of the m-e.t . current was 20 microM in Cs saline . The addition of 50-200 microM-Ca to the isotonic Ba saline could maintain the m-e.t . current . The m-e.t . current was observed in isotonic Ca and in Sr salines . Isotonic Ba, Mg and Mn salines were enriched with 1-2 mM-Ca in order to generate the m-e.t . current . The permeabilities of the divalent cations relative to Cs were calculated from the reversal potentials, and the sequence of permeabilities among divalent cations was Ca greater than Sr greater than Ba greater than Mn greater than Mg . Step-like m-e.t . currents were observed in Cs saline . The smallest step amplitude with clear resolution had a conductance of 49.7 +/- 4.5 pS (mean +/- S.D., n = 7 cells) . This is likely to be an elementary m-e.t . channel conductance.(ABSTRACT TRUNCATED AT 400 WORDS) J Invest Dermatol, 1985 Feb, 84(2), 149 - 53 Freeze-fracture cytochemical study of membrane systems in human epidermis using filipin as a probe for cholesterol; Kitajima Y et al.; Filipin (a polyene antibiotic) interacts specifically with cholesterol in membranes, producing characteristic 25 nm-diameter deformation (pitlike lesions) within the membrane plane detectable by freeze-fracture electron microscopy . Utilizing this probe, the distribution of cholesterol molecules in membranes and in lamellar structures between horny cells was investigated in human skin . The plasma membranes of basal, spinous, and granular cells reacted extensively with filipin except for desmosomal membrane portions . However, the plasma membranes of horny cells were rarely labeled with filipin, while lamellar structures between horny cells were well labeled . These observations indicate the distinct difference in susceptibility to filipin among the plasma membranes of viable cells and horny cells, and the lipid lamellar structures . Whenever horny cell plasma membranes were affected with filipin, they revealed a low deformability showing shallow pits or low protrusions . This low deformability may be due to greater membrane rigidity rather than a lower content of cholesterol, although the possibility of a low amount of cholesterol cannot be excluded . Lamellar bodies in granular cells were well labeled in the limiting membranes but poorly labeled in the internal lamellar structures . The regions of gap junctions were absolutely unlabeled . Filipin-cholesterol complexes were produced very close to the junctional strands but did not appear to disrupt the junctional structure of tight junctions . Nuclear membranes were affected only in the outer membrane with filipin . These results suggest that keratinocytes undergo a distinctive reduction in membrane deformability or in free-cholesterol content at the transition from living to dead cells, and display a heterogeneity in cholesterol distribution in human epidermal cell membranes. Gen Physiol Biophys, 1985 Feb, 4(1), 35 - 54 The study of volt-ampere characteristics of ionic channels formed by gramicidin A; Passechnik VI et al.; A method of measurement of the non-linearity coefficient of volt-ampere characteristics of the type i(U) approximately = U(1 + beta U2) has been developed for ionic channels formed by gramicidin A, using the third harmonic of the membrane current . The shape of the volt-ampere characteristics (VA) of ionic channels formed by gramicidin A did not depend on the antibiotic concentration in the membrane . The coefficient beta of non-linearity of VA of membranes modified by gramicidin A depended on electrolyte concentration "c" and it increased proportionally with the lg c from -17 V-2 at 0.03 mol/l KC1 to 8 V-2 at 3.4 mol/l KCl, and it was zero at co = 0.3 - 1 mol/l KCl . Egg lecithin and glycerol monooleate (GMO) membranes differ in their co values . The substitution of K+ for Li+ of the membrane solvent (n-heptane for n-hexadecane) did not influence the value of beta; the same applied for GMO membranes without any solvent . In a number of membranes, spontaneous change of the non-linearity coefficient with time observed after the membrane formation, as well as jumps of the non-linearity coefficient at a practically unchanged membrane conductivity . An analysis of some theoretical models of the ion transport through the channel has shown that, at voltages above 200 mV, these models provide rather small values of beta, or extremely high VA non-linearity. Nucleic Acids Res, 1985 Jan 25, 13(2), 595 - 603 Kinetic evidence that echinomycin migrates between potential DNA binding sites; Fox KR et al.; The hypothesis that echinomycin locates its preferred nucleotide sequences in DNA by a process of "shuffling" between potential binding sites has been tested . Immediately after reacting with calf thymus DNA the antibiotic is relatively weakly bound inasmuch as the complex dissociates quite rapidly when detergent is added . If the complex is allowed to equilibrate for various periods of time after mixing, an increasing proportion of the bound antibiotic dissociates slowly on addition of detergent . The kinetics of appearance of the slowly-dissociating form, and its dependence upon ionic strength, are fully consistent with the shuffling model . In contrast the dissociation profiles from poly(dG-dC) and poly(dA-dT) are independent of mixing time. Biochem Pharmacol, 1985 Jan 15, 34(2), 243 - 8 In vivo inactivation of formylglycinamidine ribonucleotide synthetase in rat hepatoma; Elliott WL et al.; The antitumor drug acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, irreversibly inactivated in vivo formylglycinamidine ribonucleotide synthetase (FGAM synthetase, EC 6.3.5.3) in transplantable rat hepatoma 3924A while the activity in host liver remained unchanged . At acivicin doses of 1.0 and 5.0 mg/kg body weight, enzyme activity in the hepatoma decreased to 26 and 5%, respectively, after 2 hr . The activity of the in vivo inactivated hepatoma 3924A enzyme could not be restored by gel filtration or 40 hr of dialysis . In the absence of L-glutamine, acivicin in vitro inactivated both liver and hepatoma FGAM synthetase in a time-dependent fashion, with an inactivation constant Kinact = 66 microM and a minimum inactivation half-time T = 1.0 min . In the presence of L-glutamine, competitive inhibition was observed with a Ki = 5 microM . Protection against in vitro inactivation was observed in the presence of 1 mM L-glutamine, suggesting that L-glutamine concentrations are important in the selective toxicity of acivicin on hepatoma cells in vivo . Irreversible inhibition of FGAM synthetase by acivicin is consistent with the view that this antibiotic is an active site-directed affinity analog of L-glutamine and indicates that this enzyme is a sensitive target of acivicin action. Nucleic Acids Res, 1985 Jan 11, 13(1), 195 - 205 Completion of the nucleotide sequence of the central region of Tn5 confirms the presence of three resistance genes; Mazodier P et al.; The DNA sequence of the region located downstream from the kanamycin resistance gene of Tn5 up to the right inverted repeat IS50R has been determined . This completes the determination of the sequence of Tn5 which is 5818 bp long . The 2.7 Kb central region contains three resistance genes: the kanamycin-neomycin resistance gene, a gene coding for resistance to CL990 an antimitotic-antibiotic compound of the bleomycin family and a third gene that confers streptomycin resistance in some bacterial species but is cryptic in E . coli . A Tn5* mutant able to express streptomycin resistance in E . coli was isolated . With this mutant, it was demonstrated that in E . coli the expression of the three resistance genes is coordinated in a single operon. Biochim Biophys Acta, 1985 Jan 10, 812(1), 193 - 8 The kinetics of colloid osmotic hemolysis . I . Nystatin-induced lysis; Pooler JP; A kinetic model of colloid osmotic hemolysis for cation-permeable cells has been developed . The model consists of three essential components . The first is a set of flux equations, under the assumption that the membrane potential is equal to the chloride equilibrium potential and that cation fluxes are described by the Goldman flux equation . The second is the osmotic equilibrium model of Freedman and Hoffman that takes into account the non-ideal osmotic behavior of erythrocytes . The third is an empirical relation between hemolysis and cell volume, developed from the lysis behavior in hypoosmotic media . Model simulations are compared with lysis experiments using the antibiotic nystatin to raise cation permeability . The form of the kinetics and inhibition of lysis by sucrose are described well by the model . In additional lysis experiments at different external pH the small pH dependence is accounted for by the model. J Biol Chem, 1985 Jan 10, 260(1), 392 - 9 Dihydrofolate reductase . The stereochemistry of inhibitor selectivity; Matthews DA et al.; X-ray structural results are reported for 10 triazine and pyrimidine inhibitors of dihydrofolate reductase, each one studied as a ternary complex with NADPH and chicken dihydrofolate reductase . Analysis of these data and comparison with structural results from the preceding paper (Matthews, D.A., Bolin, J.T., Burridge, J.M., Filman, D.J., Volz, K.W., Kaufman, B . T., Beddell, C.R., Champness, J.N., Stammers, D.K., and Kraut, J . (1985) J . Biol . Chem . 260, 381-391) in which we contrasted binding of the antibiotic trimethoprim (TMP) to chicken dihydrofolate reductase on the one hand with its binding to Escherichia coli dihydrofolate reductase on the other, permit identification of differences that are important in accounting for TMP's selectivity . The crystallographic evidence strongly suggests that loss of a potential hydrogen bond between the 4-amino group of TMP and the backbone carbonyl of Val-115 when TMP binds to chicken dihydrofolate reductase but not when it binds to the E . coli reductase is the major factor responsible for this drug's more potent inhibition of bacterial dihydrofolate reductase . A key finding of the current study which is important in understanding why TMP binds differently to chicken and E . coli dihydrofolate reductases is that residues on opposite sides of the active-site cleft in chicken dihydrofolate reductase are about 1.5-2.0 A further apart than are structurally equivalent residues in the E . coli enzyme. J Biol Chem, 1985 Jan 10, 260(1), 381 - 91 Refined crystal structures of Escherichia coli and chicken liver dihydrofolate reductase containing bound trimethoprim; Matthews DA et al.; Refined crystal structures are reported for complexes of Escherichia coli and chicken dihydrofolate reductase containing the antibiotic trimethoprim (TMP) . Structural comparison of these two complexes reveals major geometrical differences in TMP binding that may be important in understanding the stereo-chemical basis of this inhibitor's selectivity for bacterial dihydrofolate reductases . For TMP bound to chicken dihydrofolate reductase we observe an altered binding geometry in which the 2,4-diaminopyrimidine occupies a position in closer proximity (by approximately 1 A) to helix alpha B compared to the pyrimidine position for TMP or methotrexate bound to E . coli dihydrofolate reductase . One important consequence of this deeper insertion of the pyrimidine into the active site of chicken dihydrofolate reductase is the loss of a potential hydrogen bond that would otherwise form between the carbonyl oxygen of Val-115 and the inhibitor's 4-amino group . In addition, for TMP bound to E . coli dihydrofolate reductase, the inhibitor's benzyl side chain is positioned low in the active-site pocket pointing down toward the nicotinamide-binding site, whereas, in chicken dihydrofolate reductase, the benzyl group is accommodated in a side channel running upward and away from the cofactor . As a result, the torsion angles about the C5-C7 and C7-C1' bonds for TMP bound to the bacterial reductase (177 degrees, 76 degrees) differ significantly from the corresponding angles for TMP bound to chicken dihydrofolate reductase (-85 degrees, 102 degrees) . Finally, when TMP binds to the chicken holoenzyme, the Tyr-31 side chain undergoes a large conformational change (average movement is 5.4 A for all atoms beyond C beta), rotating down into a new position where it hydrogen bonds via an intervening water molecule to the backbone carbonyl oxygen of Trp-24. Arthroscopy, 1985, 1(3), 194 - 7 The septic knee--arthroscopic treatment; Jackson RW; It is well known that infection of a major weight-bearing joint can be a disastrous occurrence . Arthroscopy has been found to aid immeasureably in the diagnosis and treatment of this condition . Under arthroscopic control, adhesions can be broken down, necrotic tissue can be lavaged from the joint and, following the installation of drainage tubes, the processes of distension and irrigation can be carried out . By so doing, and in conjunction with systemic antibiotic therapy, a significant improvement in results of sepsis in major joints has been achieved, with all cases so treated being considered good to excellent at follow-up . It may be that the major benefit of the distention/irrigation method lies in the distension process which prevents loculation of necrotic tissue in the recesses of the joint and also prevents adhesion formation which might later restrict range of motion. Ann Urol (Paris), 1985, 19(6), 371 - 5 {Treatment of recurrent urogenital infections by immunomodulation}; Henocq E et al.; In recurrent urogenital infections in which no curable cause can be found, long term antibiotic therapy is often the only possible form of treatment . After performing appropriate skin tests, the authors evaluated the effectiveness of vaccination consisting of antigen therapy and an immunostimulant, P 40, in 20 patients . The recurrent infections were controlled in the cases in which this combination was used; in half of the cases, maintenance vaccination was required for a period of 2 or 3 years. Zentralbl Mikrobiol, 1985, 140(8), 641 - 7 Evaluation of stability of oxytetracycline-HCl to sterilization levels of gamma radiation; Tawfik ZS; The effect of gamma irradiation at different dose levels (from 5 to 50 KGy) on the solid state of the antibiotic oxytetracycline-HCl was examined . The results obtained showed no effect on the biological activity of the compound, as investigated by the bioassay technique . The physicochemical properties of the antibiotic were not altered by irradiation dose levels up to 40 KGy . The UV-visible spectra of all irradiated samples showed no changes . The I.R . spectra of oxytetracycline, exposed to dose levels higher than 40 KGy, showed, however, definite destruction in the chemical structure of the antibiotic . HPLC separation of samples, irradiated at 45 KGy, showed the presence of new degradation products . Accordingly, sterilization of oxytetracycline by use of gamma irradiation could be considered safe and applicable, since sterilization doses are usually considered to be less than 30 KGy. Gene, 1985, 39(2-3), 155 - 63 High-copy-number transformants and co-transformation in Dictyostelium; Nellen W et al.; We have recently established a DNA-mediated transformation system for Dictyostelium . The vector (pB10) contains the promoter from the Dictyostelium actin 6 gene fused to the NmR gene from Tn5 which confers resistance to antibiotic G418 . Dictyostelium cells can be stably transformed and express kanamycin phosphotransferase (APHII) . There is an average of three to five copies of vector DNA in transformed populations . We have fused an A + T-rich region containing the 3' end of the Dictyostelium actin (Act) 8 gene to the end of the Act6-NmR fusion . Though the fragment is inserted in reverse orientation, this adds a transcription termination and/or 3' processing site and results in the formation of a discretely sized mRNA from the Act6-NmR gene fusion . Using this vector, the number of transformants increases by approx . 5-10-fold . We also describe conditions that allow for the isolation of transformants having a high copy number of vector DNA per cell (approx . 150 copies/cell) . In addition, we show that cells can be co-transformed with the transformation vector and other pBR322 derivatives . Both plasmid DNAs are present in transformed Dictyostelium cells in high-Mr DNA . When cells are grown under selective conditions in the presence of the antibiotic G418, both DNAs are present in high copy number and Dictyostelium genes present on both vectors are transcribed and are properly regulated under the conditions examined . These modifications of the original transformation system should facilitate the introduction of modified genes into Dictyostelium to study gene regulation during development and allow one to examine the effects of high gene dosage. Ann Rech Vet, 1985, 16(4), 297 - 303 {Influence of rearing conditions on the frequency of diarrhea in newborn calves and the efficacy of oral treatment}; Vallet A et al.; A survey was carried out in 181 holdings of various production types to measure the influence of calf housing conditions and feeding of cows during late pregnancy on the frequency of calf diarrhea and an oral treatment efficiency . A second objective was to compare the efficiency of the different oral rehydratants used . The frequency of diarrhea was 51% . Slightly more than half the cases occurred during the first week of life . The dam's unadequate feeding increased morbidity (53% versus 47% with adequate feeding) . We were unable to measure the efficiency of good housing conditions, because only five holdings fitted the quality criteria which had been initially specified . In the other holdings, the cohabitation was found to be less harmful than separation in bad conditions: too many calves together, too small an area per animal, draughts or deficient air removal . Therapy efficiency was not significantly higher when appropriate feeding was given than with unadequate feeding . Treatment efficiency by an oral rehydratant only was lower with calves which were housed with their dam's than when they were outdoors . Three rehydratants, Electydral ND, Biodiet ND, Ionidiar ND had similar results that were significantly higher than those of the others . With the sodium acetate-based formula, Electydral ND, 30% of the calves recovered when it was given alone for 36 hours, 96% recovered when it was given for 72 hours, combined with oral antibiotic therapy for 36 hours. Ann Fr Anesth Reanim, 1985, 4(6), 521 - 3 {Drug-induced agranulocytosis . Discussion of the responsibility of metronidazole}; Martin C et al.; A case of severe agranulocytosis is reported in a 43 year old white male with Guillain-Barre syndrome . This patient was treated for an acute aspiration pneumonia and received several antibiotic regimens . An acute agranulocytosis occurred during the stay in the intensive care unit and was followed by a severe septic shock . Bone marrow aplasia was confirmed by needle aspiration . Metronidazole was withdrawn and agranulocytosis improved within three days . None of the other drugs given to the patient were withdrawn . Another bone marrow examination performed several days later revealed a markedly improved granulopoiesis . The patient died with multiple organ failure . The role of metronidazole is discussed in this case as this drug seemed highly responsible for the observed agranulocytosis. Histochemistry, 1985, 83(6), 519 - 23 Ultrastructural localization of anionic phospholipids in skeletal muscle plasma membrane; Moggio M et al.; Polymyxin B was used as a probe to label anionic phospholipids in skeletal muscle plasma membrane . This antibiotic produces muscle surface membrane lesions that can be identified in both thin sections and freeze-fracture replicas . The membrane perturbations assumed a patchy distribution with a preferential localization at the level of the I band and A-I bands junction . Intramembraneous particles were also observed within the lesions . We consider the possibility that microdomains of anionic phospholipids in muscle plasma membrane may function in the binding of Ca++. Gynecol Obstet Invest, 1985, 20(4), 194 - 8 Pharmacokinetics of piperacillin in the postpartum patient; Charles D et al.; Six women were given 1 g of piperacillin on the 2nd postpartum day and serum concentrations of the drug were measured at 0.5, 1, 2, and 4 h after infusion . The same women returned for an identical test 6 months later and hence served as their own controls . A second group of 6 women were treated identically except that they received the first dose of piperacillin on the 3rd postpartum day . The serum levels of antibiotic were consistently lower during the puerperium than at 6 months . The levels obtained at 2 compared to 3 days post partum were similar, but were about one half the levels obtained at 6 months post partum . These results indicate that antibiotic therapy for postpartum endomyometritis may need to take account of the fact that the altered pharmacokinetics of pregnancy persists into the puerperium . If used in this setting, the dose of piperacillin may need to be increased by 50% over the normal adult dose. Z Parasitenkd, 1985, 71(6), 699 - 704 Interaction of aminoglycosides and ionophores in the killing of Crithidia fasciculata; Millgram MA et al.; Crithidia fasciculata was utilized as a prescreen to determine the antiprotozoal action of aminoglycoside antibiotics alone and in combination with surface-altering agents . Paromomycin was tested with the carrier ionophores nigericin and valinomycin, the channel ionophore gramicidin and the polyene antibiotics amphotericin B and nystatin . After exposure to the drugs in suspension, organisms were plated out to determine the survival of C . fasciculata . Killing was time dependent for both the antibiotic and the ionophore . Paromomycin action was found to be potentiated by all the surface altering agents . The aminoglycosides kanamycin, gentamycin and streptomycin were studied alone and in combination with nigericin . Synergistic effects were demonstrated both with kanamycin and gentamycin in combination with nigericin . Streptomycin was ineffective both alone and with surface-altering agents. Vet Med Nauki, 1985, 22(7), 105 - 9 {Trial of kormogrisein-40 as a growth stimulant in pigs}; Ilieva I et al.; An experiment was carried out with 36 pigs, weighing 8 to 70 kg, divided into 4 groups to test the growth-promoting effect of kormogrisin-40 given with the feed . The animals were fed on one and the same standard combined feed--a basic ration to which antibiotics were added in the form of a premix as follows: group I (controls); group II--zinc-bacitracin in conc . of 40 ppm; group III--grisin in conc . of 5 ppm; and group IV--grisin in conc . of 12 ppm . It was ascertained that growth stimulation was best manifested with group IV--the average daily gain increased by 17 per cent, and the consumption of feed per kilogram of gain decreased by 13.2 per cent . Second in effect ranked group III--13.0 and 9.6 per cent respectively . When concentrations of 5 and 12 ppm of grisin were used with pigs, and these were slaughtered without observing any withdrawal times there were residual amounts of the antibiotic in the meat and the parenchymal organs. Ann Med Interne (Paris), 1985, 136(2), 129 - 32 {Choriocarcinomatous neoplastic pulmonary embolism . A case}; Liot F et al.; Massive obstruction of the right branches of the pulmonary artery by choriocarcinomatous cells was found at embolectomy in a 36 year old woman who had had a hydatidiform mole 10 years previously . Several febrile lung infections resistant to antibiotic therapy over an 11 months period, had led to a reduction in the volume and vascularisation of the right lung . The diagnosis of recurrent pulmonary embolism was only suspected when a further embolic episode occurred after curettage for a spontaneous abortion at 9 weeks of pregnancy . The diagnostic value of increased HCG was masked by the pregnancy . The patient died a few days after surgery despite administration of chemotherapy postoperatively . The authors discuss the problems in the diagnosis of recurrent pulmonary embolism in the absence of a suggestive cause and the problem of detecting the tumoural nature of these emboli. Soc Sci Med, 1985, 21(8), 899 - 907 Predictors of dentists' level of knowledge regarding the recommended prophylactic regimen for patients with rheumatic heart disease; Sadowsky D et al.; Maintaining knowledge of clinical practices, conforming to the latest scientific information, is a major challenge for health professionals . The study aims were to measure clinicians' knowledge and to determine what social factors could best explain and predict those dental clinicians who are most knowledgeable about current expert recommendations for the use of appropriate antibiotic regimens for patients at risk for bacterial endocarditis . Telephone interviews were conducted with 322 New York State dentists, assigned to the study by a computer-generated randomization procedure from lists of oral surgeons, urban general practitioners and rural general practitioners . Data demonstrated extraordinary differences in level of knowledge between oral surgeons and general practitioners, while the level of knowledge between urban and rural general practice groups was quite similar . General Linear Model (GLM)-based analyses indicated that practice size, rationalization of practice, and practice setting and affiliations contributed to the explanation of knowledge level among general practitioners, when adjusted for age . R2s for each of those variables and age, ranged from a low of 0.132 to a high of 0.334 . Age made a significant contribution to the explanation of knowledge level in all of the models presented, while the explanatory power of the practice structure variables varied according to respondent's locale (urban vs rural) and age (younger vs older) . In order to assess the impact of these structural variables, they were dichotomized (high-low) and entered into a GLM program which accounted for age and locale . Differences in excess of 20 points (on a 0-100 knowledge scale) were sometimes noted.(ABSTRACT TRUNCATED AT 250 WORDS) J Gynecol Obstet Biol Reprod (Paris), 1985, 14(5), 647 - 51 {Microsurgical treatment of tuboperitoneal lesions . II . Results of the release of adhesions: apropos of 46 cases}; Aubriot FX et al.; Between April 1978 and April 1983 46 patients were operated on for division of adhesions of a first and second degree according to the Madrid classification . They were operated on by laparotomy . 36 patients, which was 78.3%, had an on-going pregnancy and 3 had an extra-uterine pregnancy, which was 6.5% . We give three reasons to explain these results: antibiotic and anti-inflammatory treatment before the operation . This is important because of the high rate of infection and in particular chlamydia trachomatis . This is on-going in these patients . A technique for division of adhesions that was carried out according to a precise and stereotyped protocol used by all three operators . a follow-up of 43 out of these 46 patients that allowed them to be treated in the months following surgery to deal with other factors contributing to lowered fertility. Int J Clin Pharmacol Res, 1985, 5(5), 331 - 40 Comparison between penetration of amoxicillin combined with carbocysteine and amoxicillin alone in pathological bronchial secretions and pulmonary tissue; Braga PC et al.; Patients with chronic bronchitis were treated orally with either amoxicillin (500 mg) alone or in combination with carbocysteine (150 mg), thrice daily for five days, in order to assess whether the combination allows higher antibiotic levels to be obtained in bronchial mucus than those obtained from amoxicillin alone . Serum and mucus levels were determined for each patient at first and fifth day of the two drug regimens . The levels of amoxicillin in the lung tissue collected in patients undergoing pulmonary surgery were also determined after a single oral dose of amoxicillin (1 g) or of amoxicillin (1 g) plus carbocysteine (300 mg) . In the bronchial secretions, at the same plasma concentrations, amoxicillin levels were statistically higher after administration of combined substances . These findings indicate the presence of a pharmacokinetic synergism between these compounds, which allows amoxicillin to penetrate more easily through the hemato-bronchial barrier . The association of amoxicillin and carbocysteine, determining an increase of the quantitative levels of antibiotic in the bronchial secretion (also if it is purulent), performs a sterilizing action in a short time with significant therapeutic advantages. Acta Obstet Gynecol Scand, 1985, 64(5), 381 - 6 A prospective study of drug use, smoking and contraceptives during early pregnancy; Sandahl B; In a prospective study, 2436 women were interviewed regarding contraceptive technique used before pregnancy, on drug use, exposure to X-rays, smoking habits, and vaginal bleeding during the first 17 weeks of pregnancy . The study was conducted in Malmo during 1979 and early 1980 . The study, compared with two similar Swedish studies made in 1963-65 in Malmo and a multicenter study from 1973-74, shows a drastic reduction of psychotropic drug use, from 13.5% to 3.0% and of hormone use from 3.75 to 1.1% . The use of analgetics, however, shows an increase, from 27% to 60.7% . For antibiotic and antihistamine use there is little or no difference . The study shows no connection between drug use and fetal malformation . Smoking habits have changed--the number of non-smokers is the same but the proportion of heavy smokers (more than 10 cigs/day) has decreased from 8.9% to 1.5% . 18 (0.8%) women become pregnant while using oral contraceptives and 13 (0.5%) with an IUD in place. Respiration, 1985, 48(2), 122 - 6 Inhaled beclomethasone dipropionate in acute infections of the respiratory tract; Frank A et al.; 100 patients with acute tracheitis, tracheobronchitis or bronchitis were randomly allocated to receive inhaled beclomethasone dipropionate (BDP) 100 micrograms qds or placebo as an adjunct to oral antihistamine and a tetracycline antibiotic . 2 patients were withdrawn from analysis, leaving 49 patients in each group . There was no evidence that inhaled BDP conferred any benefit or detriment on the progress of the condition as assessed by daily symptom scores and weekly clinic visits for up to 2 weeks . The same conclusion maintains when the patients were subdivided into two grades of severity as assessed by the physician when the patient first presented . Inhaled BDP would seem to have no role in the inflammatory process associated with those acute infections of presumed viral origins. Infection, 1985, 13 Suppl 1, S151 - 5 Tolerance in patients with terminal renal insufficiency of high doses of cefotaxime; Hoffler D et al.; Eleven patients with terminal renal insufficiency requiring dialysis were treated with 3 X 2 g cefotaxime in an open study lasting five days when the clinical findings strongly indicated a serious bacterial infection . The effect of the administration of the high-dose antibiotic on the coagulation system (Quick test, partial thromboplastin time, thrombin time, antithrombin III and platelets) and on brain function (EEG) was investigated . The serum levels showed that the serum concentrations were not abnormally high in cases of terminal renal insufficiency requiring dialysis . In contrast to previous investigations in other beta-lactam antibiotics, no changes in the coagulation system or EEG occurred . On the basis of these findings, no reduction in the dose appears necessary for cefotaxime, if therapy does not exceed five days. Clin Ther, 1985, 7(5), 593 - 9 Nebulized amoxicillin in chronic purulent bronchiectasis; Stockley RA et al.; Nebulized amoxicillin (500 mg twice a day) was given for four months to six patients with bronchiectasis . The patients had continually produced purulent secretions, which had failed to clear (purulent to mucoid) when amoxicillin was given orally (3 gm twice a day) . All patients found the nebulization technique acceptable, and no acute effect on lung function was seen . There were significant reductions in sputum purulence (P less than 0.025) and volume (P less than 0.05) and a mean (+/- SD) increase in peak expired flow rate (P less than 0.05) from 230.5 +/- 79.2 L/min to 255 +/- 90.1 L/min . These improvements occurred despite the fact that apparently resistant bacteria were cultured . No adverse effects were noted . The response to nebulized amoxicillin after failure with the same drug given orally suggests that local concentrations of antibiotic in the lungs of these patients is important. Nephron, 1985, 41(2), 161 - 5 Cefuroxime pharmacokinetics in continuous and intermittent peritoneal dialysis; Chan MK et al.; Pharmacokinetics of cefuroxime was studied in patients on continuous ambulatory or intermittent peritoneal dialysis . A single intravenous bolus (15 mg/kg) of cefuroxime provided a mean serum concentration of 86 mg/litre 5 min, 40 mg/litre 1 h, 163 mg/litre 24 h after the injection . The peritoneal clearance of cefuroxime varied widely among different individuals, ranging from 1.45 to 6.17 ml/min with a mean of 3.59 ml/min during 4-hour exchanges, and from 0,52 to 11.3 ml/min during 2-hour exchanges . A single injection (15 mg/kg) of the antibiotic could not provide satisfactory antibiotic concentrations in peritoneal effluent during peritoneal lavage . When cefuroxime had been added to peritoneal dialysis solution before the solution was instilled into the peritoneal cavity, a significant decrease in cefuroxime concentration occurred in the peritoneal effluent even after a short equilibration time . Furthermore, cefuroxime concentrations measured in residual dialysis solutions in the plastic bags ranged from 44.3 to 1,351% of the concentration of cefuroxime calculated from the added doses, indicating that despite great care, mixing of the antibiotic with dialysis solutions in plastic bags was far from uniform. Microbiol Immunol, 1985, 29(6), 479 - 85 Actinomyces viscosus cell-free synthesis of extracellular slime polysaccharide; Ooshima T et al.; A cell-free extract of Actinomyces viscosus T14Av catalyzed the synthesis of extracellular N-acetylglucosamine-rich slime polysaccharide . The activity was localized in the cytoplasmic membrane fraction and required the presence of ADP-glucose and UDP-N-acetylglucosamine . Maximal activity was demonstrated at pH 7.5 and also required the presence of divalent cations such as Mg2+ or Mn2+ . Extracellular slime appeared to serve as a primer for slime biosynthesis . The antibiotic tunicamycin acted as an inhibitor of slime formation . However, another glucosamine analogue, amphomycin, as well as the antibiotic bacitracin produced moderate stimulatory effects on slime biosynthesis. Dermatologica, 1985, 171(2), 112 - 6 Malignant pyoderma . Report of a case associated with a disorder of the immune system; Aram H; A 41-year-old man developed multiple suppurative ulcers and subcutaneous inflammatory nodules and abscesses on the face, the trunk and the extremities . Repeated bacterial and fungus cultures gave nonspecific and inconstant results . Light-microscopic studies showed diffuse inflammatory reaction in the dermis with abscess formation and tissue destruction . There was no evidence of blood vessel inflammatory changes . The course of the disease was characterized by marked chronicity and partial response to systemic steroid and antibiotic therapy . Treatment with clofazimine resulted in a marked improvement of the lesions . Laboratory test results suggest that a deficiency of cell-mediated immunity, associated with increased concentrations of immunoglobulins, may have been the pathogenic event in this case. Eur J Cancer Clin Oncol, 1985 Jan, 21(1), 23 - 30 Relationship between leukemic cell retention of cytosine arabinoside triphosphate and the duration of remission in patients with acute non-lymphocytic leukemia; Preisler HD et al.; Bone marrow cells were obtained from patients with acute non-lymphocytic leukemia immediately prior to the administration of cytosine arabinoside/anthracycline antibiotic remission induction therapy . The ability of the leukemic cells to take up and phosphorylate cytosine arabinoside (araC) and to retain cytosine arabinoside triphosphate (araCTP) was measured and compared to the outcome of remission induction therapy and the duration of remission . While the outcome of remission induction therapy was unrelated to cellular metabolism of araC, the duration of remission was highly correlated with araCTP retention . A comparison of the remission durations of patients treated on successive chemotherapeutic protocols suggests that the benefits of intensive remission consolidation therapy may be limited to patients whose leukemic cell retention of araCTP is low and that aggressive consolidation chemotherapy may reduce the prognostic significance of araCTP retention. Ann Med Interne (Paris), 1985, 136(4), 306 - 10 {Course of gonococcal arthritis: a retrospective study of 42 cases}; Dougados M et al.; The authors report a retrospective study of the evolution os gonococcal arthritis after antibiotic therapy . The prognosis i-good but the speed of recovery depends on early treatment . Post-septic arthritis is common (13/42) and requires local treatment . The diagnosis of post-infective and/or reactive gonococcal arthritis is discussed. Anat Embryol (Berl), 1985, 172(1), 97 - 9 Absence of filipin-sterol complexes from the ciliary necklace of ependymal cells; Cuevas P et al.; The polyene antibiotic filipin reacts specifically with membrane cholesterol and produces membrane perturbations . Prefixed vibratome slices of cat ependymal cells were treated with a glutaraldehyde solution containing 300 microM filipin . Freeze-fracture of these cells revealed numerous 25-30 nm protuberances on fracture faces (filipin-sterol complexes) in the ciliary membrane . In the ciliary necklace, however, these filipin-sterol complexes were absent . These results suggest that the ciliary necklace has a low cholesterol content. Acta Chir Hung, 1985, 26(3), 141 - 3 Experimental retroperitoneal infection; Kisida E et al.; A bacterial inoculum was positioned intraperitoneally and retroperitoneally in animals who had been treated with various antibiotic programs . The results indicate that the retroperitoneal tissue is more resistant to severe infectious complications than the general peritoneal cavity. Rev Chir Orthop Reparatrice Appar Mot, 1985, 71(4), 235 - 40 {Treatment of acute pyogenic arthritis of major joints of the limbs}; Travers V et al.; The authors have treated 52 cases of septic arthritis of major joints . When aspiration contain an opaque fluid, conservative treatment with antibiotic therapy and immobilisation obtained healing in half of the patients . Surgical lavage of the joint was needed on 21 occasions with healing in 15 . Synovectomy was performed in 8 cases and was indicated only at the stage of pyogenic synovitis before the development of pyogenic arthritis . When the latter stage was reached, arthrodesis was indicated . It was performed primarily on 6 occasions and secondarily once . Seven patients died . The average age was seventy years . The importance of early treatment is stressed. Drugs, 1985, 29 Suppl 5, 106 - 8 Pharmacokinetics and tissue penetration of temocillin; Lockley MR et al.; The pharmacokinetics of intravenous (bolus) temocillin 1 g were studied in 6 healthy male volunteers, and a cantharides blister method was used to estimate tissue penetration of the antibiotic . The mean elimination half-life was 4.5 hours . Temocillin penetrated blister fluid rapidly and reached concentrations of about 50% of those in serum by 2 to 3 hours after administration . Over an 8-hour period, the serum and blister fluid concentrations exceeded the MIC90 of susceptible bacteria by 2-fold or greater, suggesting that twice or even once daily dosing with temocillin may be sufficient. Nauchnye Doki Vyss Shkoly Biol Nauki, 1985, (5), 55 - 61 {Action of actinomycin D on the nucleolar function and ultrastructure of a pig embryo kidney cell culture}; Netesova MA et al.; It has been shown that the morphofunctional alterations of nucleoli in KEPV cells induced by actinomycin D at 0,05 microgram/ml proceed in two steps . During the first 3 h of actinomycin D action a level of the RNA synthesis in nucleoli falls to 25% from the initial one . Simultaneously the following morphological alterations take place: condensation of the chromatin, infiltration of nucleoli, displacement to outlining regions, increase of the dimensions and reduction of number of fibrillar centres, gradual disappearance of compact fibrillar zone and appearance looplike granular structures . During the following 3-6 h of antibiotic action the RNA synthesis falls slightly, nucleoli dimensions decrease, fibrillar micronucleoli appear. Arzneimittelforschung, 1985, 35(6), 991 - 3 Comparative pharmacokinetics of doxycycline and oxytetracycline in patients with hyperlipidemia; Wojcicki J et al.; This study examines the pharmacokinetics of lipophilic drug doxycycline (Vibramycin) and water-soluble antibiotic oxytetracycline hydrochloride (Oxyterracyna) in patients with hyperlipidemia type IIa and type IV according to Fredrickson . Antibiotics were administered orally as a single dose and determined in plasma by a fluorimetric method . The calculations were performed by aid of a computer . Increased concentrations of doxycycline were found; they were higher in type IIa, as compared with type IV . Area under the curve (AUC) and peak concentrations as well as rate constant for elimination in subjects with type IV were significantly elevated; volumes of distribution and total body clearance were markedly diminished . Decreased concentrations of oxytetracycline, area under the curve, peak concentration and rate constant for elimination were observed in patients with type IV . In both types of hyperlipidemia volume of distribution was increased and half-life in patients with type IV was significantly prolonged . The findings show that hyperlipidemia can be an important factor of drug action . Alterations of pharmacokinetics of lipophilic doxycycline and hydrophilic oxytetracycline were contrasting. Arzneimittelforschung, 1985, 35(6), 958 - 60 In vitro effects of ureidopenicillins on human polymorphonuclear leukocytes; Burgaleta C et al.; The in vitro effects of mezlocillin, azlocillin and piperacillin on chemotaxis and adhesivity of human leukocytes were comparatively studied . After incubation with all these antibiotics, chemotactic and adhesivity counts were similar to those of the antibiotic-free cells . Scanning electron microscope examination showed enlargement of surface and length measurements after incubation with azlocillin (P less than 0.005 and P less than 0.001) and mezlocillin (P greater than 0.05 and P less than 0.05), while piperacillin produced no alteration . These findings could provide additional information in the study of leukocyte/antibiotics interactions. Vutr Boles, 1985, 24(3), 114 - 8 {2 cases of legionellosis in Greek citizens}; Kadiian K et al.; Two cases of legionella pneumonia are reported in Greek citizens, treated at the Institute for Treatment of Foreigners--Medical Academy, Sofia . The patients mentioned are with grave basic diseases--pulmonary carcinoma . In one of them pneumonia was with a lethal end in spite of the adequate antibiotic therapy. Vutr Boles, 1985, 24(1), 127 - 33 {Invasive aspergillosis in patients who died from acute leukemia}; Gerdzhikova P et al.; The necropsy material with acute leukosis (166 deceased) was studied in order to establish the incidence of invasive aspergillosis . It was established in 16 of the deceased (9,64%): aspergillosis pneumonia--in 5 cases, aspergillosis sepsis--in II, with invasion of lungs, brain, spleen, liver, myocardium and other organs . Clinically aspergillosis was not distinguished . Continuous septic temperature, not influenced by antibiotic therapy should draw the attention to the presence of aspergillosis . The factors, preconditioning aspergillosis infection are stressed upon: immune-suppressive treatment in acute leukosis, granulocytopenia, continuous preceding antibiotic therapy, etc . The difficulties in the clinical differentiation of the infection are emphasized . With a view to the high incidence and lethality of aspergillosis in acute leukosis, the introduction of modern diagnostic methods and treatment are underlined to be necessary. Tierarztl Prax Suppl, 1985, 1, 71 - 8 {Postoperative wound infection in the horse}; Diehl M et al.; A systemic investigation of wound infection in the horse after operative treatment of large wounds reveals that the age of the wound is of critical importance . The limit for an uncomplicated healing process lies around four hours . The duration of the operation itself is of little significance, the location of the lesion on the body of the horse, however, plays a major role . The pattern of isolated bacterial organisms is discussed in relation to the duration of hospital treatment . It is concluded that a systemic antibiotic therapy is of no value and that a local antibiotic therapy is only indicated in rare instances . Such a treatment undoubtedly favours the resistance of bacteria against various chemotherapeuticals, which unfavourably influences wound healing. Tissue Cell, 1985, 17(2), 177 - 87 Filipin-cholesterol complexes in plasma membranes and cell junctions of Tenebrio molitor epidermis; Berdan RC et al.; The polyene antibiotic filipin combines with cholesterol in membranes to form complexes that are readily identifiable in the electron microscope . The distribution of filipin-cholesterol (FC) complexes is most easily studied by freeze-fracture . Larval epidermis of Tenebrio molitor (Insecta, Coleoptera) was maintained in vitro for 48 hr, since the electrophysiological properties of the cells are best characterized under these conditions . The cells were fixed in buffered 3.0% glutaraldehyde at RT for 15 min, transferred to fresh fixative containing 1% DMSO and filipin (final concentration; 0.5 mg/ml) for 3 hr RT . Control cells were treated in fixative containing 1% DMSO only . In freeze fracture replicas, FC complexes appear on the plasma membrane as large circular protrusions measuring 26.5 +/- 6.8 nm (x +/- s.d.) n = 50, in diameter and 17.1 +/- 2.8 nm, n = 50, in height and 11.7 +/- 2.6 nm, n = 25, in depth . Protrusions are about two times more frequent on the E face while pits are several times more frequent on the P face . FC complexes are most abundant (greater than 50/mu m2) on the basal membrane surface of the cells but are excluded from regions of hemidesmosomal plaques that anchor the cells to the basal lamina . FC complexes are also abundant on the apical surfaces of the cells where cuticle secretion occurs . In the lateral regions below the junctional belt, FC complexes are less numerous but often appear to increase in frequency in a graded fashion away from the junctional region . The septate junctions are relatively free of FC complexes except in regions where they open to form islands . These islands often contain gap junctions but the FC complexes rarely invade the particle domains of the gap junctions . Single FC complexes were seen in three out of a total of 97 gap junctions . Exposure of the epidermis to 20-hydroxyecdysone for 24 hr in vitro did not induce the appearance of FC complexes within the cell junctions. Eur Urol, 1985, 11(2), 137 - 8 Two cases of malakoplakia of the prostate; Klaaborg KE et al.; 2 further cases of malakoplakia of the prostate are reported, so that a total of 23 cases have now been described . The histological picture, as well as the methods of staining for the demonstration of the pathognomonic Michealis-Gutmann bodies are reviewed . The presence of Escherichia coli as a possible factor in the etiology is discussed . A description is given of the symptoms and physical findings in cases of prostatic malakoplakia, and the differential diagnosis, with particular reference to cancer of the prostate, is reviewed . Histology alone can provide the correct diagnosis . Finally it is emphasized that malakoplakia can be treated with long-term antibiotic therapy. East Afr Med J, 1985 Jan, 62(1), 54 - 9 Health status of teenage school boys in eastern Sudan; Rekart ML et al.; PIP: In July, 1981 a health survey of teenage boys was conducted in a medical clinic in the eastern Sudan, run by the Lalmba Association, a non-profit aid organization based in the US . The study population was a group of 231 students ranging in age from 13-18, some of whom board at the school . Data consisted of a general health questionnaire, height and weight measurements, and a thorough physical examination including stool sample . Average height and weight were both less than Western teenagers, possibly due to a diet deficient in animal and plant protein and total calories . Hematocrit levels were comparable . Stool parasites were present in 31% of those surveyed, the most common being Giardia, Entamoeba histolytica, and Hymenolepsis nana . The most common symptomatic problem was dental caries (8%) and the most common asymptomatic problems were trachoma and anemia (15% and 9% respectively) . Investigators noted an unexpected number of genitourinary abnormalities (6%) . The study population was selective in that it was the well-off portion of the teenage population in this locality . The investigators suggest that health authorities in the area distribute trachoma prophylaxis (antibiotic eye ointment) to all school age children . Ther Drug Monit, 1985, 7(1), 92 - 4 No influence of doxycycline on theophylline pharmacokinetics; Jonkman JH et al.; The influence of the antibiotic drug doxycycline on steady-state pharmacokinetics of theophylline was studied in nine healthy adults by comparing the pharmacokinetic parameters measured during a 9-day course of theophylline alone and during comedication with doxycycline . Theophylline plasma concentrations were measured by means of high performance liquid chromatography analysis . Trough theophylline plasma concentrations were measured on days 1-8 . On day 9 of each of the two periods of drug administration, a plasma concentration-time curve was evaluated . No influence of doxycycline on absorption, elimination, and volume of distribution of theophylline was found . Mean steady-state plasma concentrations were not significantly different during the two treatments . It is concluded that the drugs can be given concomitantly without any dosage adjustment of theophylline. Exp Hematol, 1985, 13 Suppl 16, 80 - 8 Management of infection in myelosuppressed patients: clinical trials and common sense; Greene WH; In the past fifteen years, enormous research effort has been expended in pursuit of the "ideal" approach to the management of infection in the myelosuppressed, i.e., granulocytopenic, patient . In the welter of clinical trials, some "commonsense" fundamentals have been lost or submerged, while other ideas seem to have become "modern myths." Among those commonsense approaches that should not be forgotten are the following: Granulocytopenia often precludes even the most skilled observer from assessing whether a febrile patient is truly infected . The epidemiology of infection at the local institution should be the principal determinant of the empiric antibiotic regimen in use . There is no ideal empiric antibiotic regimen . In particular, there is no absolute necessity for antipseudomonal penicillins, for aminoglycosides or for combinations of antibiotics . Some modern myths that seem to have been widely accepted without adequate data are: Antibiotic "synergism" is an essential prerequisite to a successful outcome of infection in the granulocytopenic patient . In the febrile granulocytopenic patient who responds to treatment, antibiotics should be continued until the granulocytopenia resolves . In the febrile granulocytopenic patient who does not respond to treatment, all such patients should receive amphotericin B for empiric antifungal treatment . These and other modern myths and aspects of common sense will be discussed in light of recent clinical trials. Jikken Dobutsu, 1985 Jan, 34(1), 1 - 16 Bacterial translocation from the intestines; Berg RD; Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal (GI) tract through the mucosal epithelium to other sites, such as the mesenteric lymph nodes, spleen, liver and blood . This paper reviews results from animal models utilized to obtain information concerning the defense mechanisms operating in the healthy host to confine bacteria to the GI tract . Gnotobiotic and antibiotic-decontaminated mice colonized with particular bacteria demonstrated that the indigenous GI flora maintains an ecologic equilibrium to prevent intestinal bacterial overgrowth and translocation from the GI tract . Studies with athymic (nu/nu) mice, thymus-grafted (nu/nu) mice, neonatally thymectomized mice, and mice injected with immunosuppressive agents demonstrated that the host immune system is another defense mechanism inhibiting bacterial translocation from the GI tract . Ricinoleic acid given orally to mice disrupted the intestinal epithelial barrier allowing indigenous bacteria to translocate from the GI tract . Thus, bacterial translocation from the GI tract of healthy adult mice is inhibited by: (a) an intact intestinal epithelial barrier, (b) the host immune defense system, and (c) an indigenous GI flora maintaining ecological equilibrium to prevent bacterial overgrowth . Deficiencies in host defense mechanisms act synergistically to promote bacterial translocation from the GI tract as demonstrated by animal models with multiple alterations in host defenses . Bacterial translocation occurred to a greater degree in mice with streptozotocin-induced diabetes, mice receiving nonlethal thermal injury, and mice receiving the combination of an immunosuppressive agent plus an oral antibiotic than in mice with only a primary alteration in host defenses . The study of bacterial translocation in these complex models suggests that opportunistic infections from the GI tract occur in discrete stages . In the healthy adult animal, bacterial translocation from the GI tract either does not occur or occurs at a very low level and the host immune defenses eliminate the translocating bacteria . Bacterial translocation does take place if one of the host defense mechanisms is compromised, such as a deficiency in the immune response, bacterial overgrowth in the intestines, or an increase in the permeability of the intestinal barrier . In this first stage, the bacteria usually translocate in low numbers to the mesenteric lymph node, and sometimes spleen or liver, but do not multiply and spread systemically.(ABSTRACT TRUNCATED AT 400 WORDS) J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 85 - 97 Pharmacokinetic considerations for the setting of in-vitro models; Lintz W; Nearly all in-vitro kinetic models hitherto employed only consider serum concentration curves of the antibiotic . Data thus obtained at best reflect the situation in septicaemia . However, they are not applicable for infections where infecting bacteria are not localized within the blood . This paper presents a method for calculating the time course of the non-protein bound drug in tissue water . The concept makes use of serum concentration curves, the extent of serum protein binding and the peak time of total drug concentration in the tissue . This is practicable since all data necessary for calculation are available experimentally . Using cefmenoxime, cefotaxime, latamoxef (moxalactam) and ceftriaxone as examples, the vast differences between the total concentration of the antibiotic in serum and the concentration of the non-protein bound antibiotic in the tissue water are demonstrated . Therefore, only the results of in-vitro experiments, which are based on time courses of the non-protein bound drug in the tissue water, are considered relevant for assessing therapeutic efficacy of an antibiotic. Eur J Respir Dis, 1985 Jan, 66(1), 47 - 9 No effect of cefaclor on theophylline pharmacokinetics; Jonkman JH et al.; The effect of the antibiotic drug cefaclor on steady state pharmacokinetics of theophylline was studied in healthy adults by comparing the pharmacokinetic parameters as found during a 9 days course of theophylline alone and as obtained during comedication with cefaclor . Theophylline plasma concentrations were measured by means of HPLC analysis . On the ninth day of each of the 2 periods of drug administration, a concentration-time curve was evaluated . It showed no influence of cefaclor on volume of distribution and clearance of theophylline and only a slight, but significant (p less than 0.05) influence on the values for Cmax and tmax after cefaclor co-treatment . It is concluded that both drugs can be given concomitantly without any dosage adjustment of theophylline. Eksp Onkol, 1985, 7(1), 48 - 52 {Hemopoietic precursor cells during the development of carminomycin resistance}; Kozinets GI et al.; A comparative quantitative investigation of colony-forming ability of mouse bone marrow hemopoietic stem cells in the case of ordinary leukemia variant (P-388) and carminomycin-resistant variant (P-388/k) was carried out . Leukemia bearing mice received single injections of increasing doses of carminomycin on the 5th day after transplantation and 24 hours later the bone marrow was investigated for quantity of colony-forming units in the spleen (CFUs) . Dynamics investigation of bone marrow cells in the case of P-388 and P-388/k (without treatment) reveals the common tendency to a decrease of these cells in the period before animal death . Sensitivity of colony forming cells (CFUs) to different doses of the antibiotic of mouse bone marrow in both cases (P-388 and P-388/k) was practically the same . Dynamics of CFUs in two populations of cells after a single injection of carminomycin in doses causing the killing of 50% of CFUs showed that the antibiotic inhibited CFUs equally (50%) . However this inhibition in case of CFUs with P-388/k leukemia was almost five times longer than in the case of ordinary P-388 one . Based on the investigations conducted the second injection of the antibiotic to mice with P-388/k leukemia on the fifteenth day after the first one may be recommended. Br J Clin Pharmacol, 1985 Jan, 19(1), 99 - 101 Lack of effect of amoxicillin on theophylline pharmacokinetics; Jonkman JH et al.; The effect of the antibiotic drug amoxicillin on steady state pharmacokinetics of theophylline was studied in healthy adults by comparing the pharmacokinetic parameters as found during a 9 day course of theophylline alone and as obtained during comedication with amoxicillin . Theophylline plasma concentrations were measured by means of h.p.l.c . analysis . On the ninth day of each of the two periods of drug administration a concentration-time curve was evaluated . It showed no influence of amoxicillin on absorption, elimination and volume of distribution of theophylline, as a result of which mean steady state plasma concentrations were not significantly different during both treatments . It is concluded that both drugs can be given concomitantly without any dosage adjustment of theophylline. Phys Med Biol, 1985 Jan, 30(1), 31 - 9 Effect of additives on liposomes: an electric birefringence study; Ruderman G et al.; Under the influence of an electric field, vesicles in suspension partially deform or orientate, rendering the medium optically birefringent . The amplitudes of the birefringence under fields of variable amplitude lead to evaluation of the anisotropy of the electrical delta alpha and optical delta G polarisabilities of the vesicles . By using pulsed fields, rates of establishment and decay of birefringence enable vesicle sizes d to be measured . Samples of 9:1 phosphatidylcholine-phosphatidylserine liposome suspension in water were studied in the presence of various additives, including sucrose, an antibiotic (streptomycin), a steroid (dexamethasone), an anaesthetic (lignocaine) and a fluidising agent (benzyl alcohol) . The changes in the three parameters delta alpha, delta G and d were different for each additive and are thought to be indicative of the mode of interaction of each . Electric birefringence also appears to be a rapid means of detecting structure changes. Poult Sci, 1985 Jan, 64(1), 59 - 64 Effect of mixed organic acid administration on blood levels of chlortetracycline in broiler chicks; Wyatt RD et al.; Male broiler chicks, when administered mixed organic acids via the drinking water for 3 days prior to water administration of chlortetracycline (CTC), showed no significant increases in the blood levels of the antibiotic . However, if the organic acids were administered simultaneously with the antibiotic, either via drinking water administration or via oral dosing, significant increases in the blood levels of the antibiotic were noted . With simultaneous administration of the antibiotic and mixed organic acids via the drinking water, a significant decrease in water intake was observed; however, in spite of the decrease in water intake and a concomitant decrease in CTC intake, significant increases in the blood levels of the CTC were still present . These data suggest that mixed organic acids, commonly used in the poultry industry, can be utilized to elicit an increase in CTC blood levels to a greater degree than would be anticipated without the use of the organic acids. Lab Anim, 1985 Jan, 19(1), 3 - 6 A comparison of subcutaneous and intraperitoneal oxytetracycline injection methods for control of infectious disease in the rat; Porter WP et al.; After receiving once daily intraperitoneal (i.p.) or subcutaneous (s.c.) injections of oxytetracycline (15 mg/100 g bodyweight) for 7 days, laboratory rats had significantly different oxytetracycline serum levels depending on the method of injection . Regardless of injection method, the biological half-life of the antibiotic was 4.25 h and serum antibiotic levels never fell below therapeutic levels for certain rat pathogens during 24 h post-injection . Severe peritonitis and cellulitis were found in rats whether injected s.c . or i.p . and some animals lost bodyweight . It appeared that either injection method would be an effective treatment for certain infectious diseases of laboratory rats but tissue damage, probably from oxytetracycline's acidity, made both methods unattractive. J Antimicrob Chemother, 1985 Jan, 15(1), 105 - 13 Inhibitory effects of gentamicin and ethacrynic acid on mammalian microsomal protein synthesis; Buss WC et al.; The ototoxic antibiotic gentamicin, and the ototoxic diuretic ethacrynic acid, both produce inhibitory effects on protein synthesis in microsomes isolated from rat brain . Inhibitory effects appear to be essentially independent of each other . The inhibitory dose-response curve for gentamicin is logarithmic, while that for ethacrynic acid is linear . The dose-response curves make gentamicin the predominant inhibitor when the drugs are combined at low concentrations and ethacrynic acid the predominant inhibitor when the drugs are combined at high concentrations . Accumulation of aminoglycoside by tissues of the inner ear may result in inhibition of protein synthesis in spite of low and transient plasma levels of the drug . Further inhibition of translation by ethacrynic acid could account, in part, for the ototoxic interaction of aminoglycosides and high ceiling diuretics. Chem Biol Interact, 1985 Jan, 52(3), 361 - 75 The in vitro interaction of naphthyridinomycin with deoxyribonucleic acids; Zmijewski MJ Jr et al.; The binding of naphthyridinomycin (NAP) to deoxyribonucleic acid was investigated using radioisotope labeled antibiotic . Dithiothreitol (DTT) enhances complex formation in a concentration dependent fashion but was found to be slightly inhibitory at concentrations above 10 mM . {C3H3}-NAP-DNA complexes, formed in the presence or absence of reducing reagents, were stable to Sephadex G-25 chromatography and precipitation with ethanol, indicating a strong bond formed between the drug and DNA . Time course studies showed that the difference between the binding of activated and non-activated antibiotic was a DTT-dependent burst . This was followed by a second phase of binding which was similar in both the activated and non-activated antibiotics . The activation of the antibiotic by DTT was a reversible reaction at pH 7.9 . The activated form at pH 5.0 was extremely stable and did not revert to the unactivated form even after an 8-h incubation period . Antibiotic-DNA complex formation was pH independent between pH 5.0 and 7.0 for activated NAP . The non-activated antibiotic bound to DNA much better at pH 5.0 than at physiological pH values . Release of antibiotic from complexes (as followed by long term dialysis) formed in the presence of DTT and at pH 5.0 was biphasic, suggesting that the drug can bind to DNA in more than one way . A constant rate of antibiotic release was observed at pH 7.9 with or without DTT . At pH 2.0 and pH 12.0, greater than 95% of the antibiotic is released from the complexes . Most of the acid released antibiotic is NAP while most of the base released antibiotic had decomposed to a more polar compound . NAP binds well to calf thymus DNA, poly(dG) . poly(dC), and T4 DNA but shows significantly less affinity for poly(dA) . poly(dT), poly(dA . dT) . poly(dA . dT), poly(dG), poly(dC), poly(dI) . poly(dC) or poly(dG . dC) . poly(dG . dC) . This specificity of NAP for DNA is similar to that observed for the pyrrolo(1,4)benzodiazepine antibiotics and saframycin A and S; all of which bind to double stranded DNA through their carbinolamine or masked carbinolamine functionalities . Two mechanisms which can explain the need for activation of NAP are also proposed. Arch Intern Med, 1985 Jan, 145(1), 114 - 6 Blood eosinophilia in patients undergoing maintenance peritoneal dialysis; Chandran PK et al.; To determine the prevalence of blood eosinophilia in patients receiving maintenance peritoneal dialysis, routine peripheral WBC counts of 49 such patients were reviewed . In 29 patients, blood eosinophilia was noted . Elevations in blood eosinophil counts tended to be mild and episodic . They were often associated with concomitant elevation of peritoneal fluid eosinophil counts . Possible predisposing factors included recent peritoneal catheter insertion and antibiotic therapy for peritonitis. Am J Dis Child, 1985 Jan, 139(1), 41 - 5 Hepatobiliary scintigraphy for cholestasis in congenital hepatic fibrosis . Diagnosis and treatment; Stillman AE et al.; A 9-year-old child with congenital hepatic fibrosis had dilated intrahepatic bile ducts and recurrent cholangitis . Choleretic agents were administered to prevent recurrent cholangitis . Response to treatment was monitored with serum bile acid concentrations and computer-assisted technetium Tc 99m iprofenin (Pipida) scintigraphy . Dehydrocholic acid with meals improved hepatobiliary excretion of the radioactive isotope and lowered serum bile acid levels but did not prevent cholangitic attacks when used alone . Sulfamethoxazole and trimethoprim used alone prevented infection, but a steady rise in serum bile acid concentrations suggested increasing cholestasis . During combined drug treatment, the patient remained free of cholangitis for at least two years . Optimal therapy of congenital hepatic fibrosis with cholestasis but without mechanical biliary obstruction may involve the combined use of a choleretic such as dehydrocholic acid plus a suppressive antibiotic. Drug Intell Clin Pharm, 1985 Jan, 19(1), 52 - 4 Feasibility and cost savings of intravenous administration of aminoglycosides in outpatients with cystic fibrosis; Bosso JA et al.; Hospitalization for some patients is often prolonged by days to weeks to complete a course of intravenous antibiotics . This is true with CF patients' who usually receive aminoglycosides throughout their hospital course . This study assesses the practicality and cost effectiveness of intravenous aminoglycoside therapy in outpatients with CF . Fifteen patients were discharged from the hospital a total of 31 times with up to three days of antibiotic, preloaded in syringes, to be administered with a portable syringe pump that delivered a dose over 40 minutes . A total of 242 drug infusions were self-administered in this manner . Flow-rate data indicated that the pumps infused at a rate within +/- 8% of their nominal rate . During the 31 courses of treatment, intravenous catheters had to be replaced on 11 occasions, but four of these episodes occurred in one patient who was treated at home for 36 days . Two malfunctions of the infusion system occurred, as did six catheter site reactions . The cost of preparing drug doses for outpatient use of this system and rental of the pump is not only less than that for in-hospital administration with piggy-back bottles (approximately $20 vs . $30/d, respectively), but totally negates the cost of the hospital room (approximately $200/d) . Outpatient administration of aminoglycoside by controlled intravenous infusion is not only convenient and safe, but results in considerable cost savings. Arch Otolaryngol, 1985 Jan, 111(1), 56 - 8 Lateral sinus thrombosis . Medical or surgical treatment? Goldenberg RA. Although it is rarely seen now, lateral sinus thrombosis may occur in either its septic or aseptic form . Septic lateral sinus thrombosis is a potentially fatal condition in which early diagnosis may be difficult because of previous antibiotic therapy . Once diagnosis is made, combined antibiotic and surgical treatment is necessary to keep the mortality rate at 25% . Aseptic lateral sinus thrombosis is a condition that is rarely fatal but that leads to symptoms of severe headache and visual impairment . The increased intracranial pressure is associated with a blockage of the dominant sinus (usually the right one) . The decision to use medical treatment alone or to combine it with surgical treatment must depend on the clinical features of each case. Neurology, 1985 Jan, 35(1), 47 - 53 The triad of neurologic manifestations of Lyme disease: meningitis, cranial neuritis, and radiculoneuritis; Pachner AR et al.; We studied 38 patients with Lyme meningitis, a newly recognized spirochetal infection . The patients characteristically had intermittent attacks of severe headache, mild meningismus, and a predominantly lymphocytic pleocytosis . In addition to meningitis, 11 patients experienced subtle encephalitic signs, 19 had cranial neuritis, most commonly unilateral or bilateral facial palsy, and 12 developed peripheral radiculoneuritis, plexitis, or mononeuritis multiplex . Without antibiotic therapy, the duration of neurologic involvement was 3 to 18 months . Although sometimes incomplete, the triad of neurologic manifestations of Lyme disease--meningitis, cranial neuritis, and radiculoneuritis--presents a unique clinical picture. Mol Gen Mikrobiol Virusol, 1985 Jan, (1), 3 - 9 {Various aspects of the use of liposomes in the diagnosis, prophylaxis and treatment of infectious diseases}; Zakrevskii VI; The literature data on preparation and properties of liposomes containing drugs, antigens and immunostimulants are reviewed . The efficiency of antibiotic-containing liposomal preparations in the treatment of infectious diseases has been demonstrated due to the directed transport of drugs into the target organs, inside cells, and to the decrease of antibiotics toxic effects . Immunostimulating and adjuvant effects of antigen-containing liposomes, particularly in combination with immunostimulants, have been described, that permits obtaining highly active diagnostic sera . The data are presented on the prospects for construction of molecular vaccines with the use of liposomes. Acta Haematol, 1985, 74(2), 116 - 7 Emergency splenectomy in hairy cell leukemia; Coser P et al.; The role of splenectomy in the treatment of hairy cell leukemia (HCL) is now well established . There are however some particular situations which indicate splenectomy as a possible emergency therapy in markedly cytopenic cases with severe antibiotic-resistant infections . The aim of the emergency splenectomy in such conditions is to temporarily increase neutrophils and to permit the improvement of the infectious disease . We describe 2 cases of HCL with severe infectious disease, successfully splenectomized. J Basic Microbiol, 1985, 25(4), 279 - 83 Synergistic effect of cobalt on the induction by A-factor of the formation of aerial mycelium and anthracyclines by a blocked mutant of Streptomyces griseus; Grafe U et al.; Cobalt ions synergistically supported the inducing effect of A-factor 1a on the formation of aerial mycelium and anthracyclines by the blocked S . griseus mutant 86 . This suggested an involvement of effector 1a in the transport or metabolism of this trace element . In accordance with the proposed role of 1a as an autoregulatory secondary metabolite, the parent strain S . griseus JA 3933 secreted 1a into the medium after a decrease of the specific growth rate and before the onset of antibiotic production. Jpn J Antibiot, 1985 Jan, 38(1), 114 - 20 {Effect of cefminox on severe infections accompanying hematological diseases}; Saito T et al.; A new antibiotic cefminox (CMNX, MT-141) was administered to 54 patients with severe infections accompanying various hematological diseases . The rate of effectiveness was 55.3% on the whole . Mild liver dysfunction was observed in 3 cases, which recovered quickly following the stop of the administration. Vet Immunol Immunopathol, 1985 Jan, 8(1-2), 171 - 82 Enhanced intraphagocytic killing of Brucella abortus in bovine mononuclear cells by liposomes-containing gentamicin; Dees C et al.; In vitro intraphagocytic killing of Brucella abortus in bovine mononuclear leukocytes was enhanced by cationic, anionic, and neutral multilamellar liposomes-containing gentamicin . Free gentamicin not entrapped in liposomes . and liposomes without antibiotic did not enhance intraphagocytic killing of B . abortus in bovine phagocytes . In vivo killing of B . abortus in guinea pigs was also enhanced by liposomes-containing gentamicin when compared to free gentamicin . Liposomes-containing alpha tocopherol acetate failed to enhance in vivo killing of B . abortus. Carcinogenesis, 1985 Jan, 6(1), 131 - 4 Cordycepin reduces the sensitivity of BALB/Mo mouse lymphocytes to the induction of sister chromatid exchanges; Majone F et al.; Lymphocytes from the spleen of BALB/Mo mice, which carry endogenous Moloney murine leukemia virus (M-MuLV), show in vitro frequencies of sister chromatid exchanges (SCEs) significantly higher than lymphocytes from control (M-MuLV free) BALB/c mice . In vitro treatment of lymphocytes with the antiviral antibiotic cordycepin (10 micrograms/ml) lowers the level of SCEs in BALB/Mo cells to the same value of BALB/c cells . M-MuLV yield is also markedly reduced in BALB/Mo lymphocytes cultured in the presence of cordycepin . The drug also abolishes the increased sensitivity of BALB/Mo lymphocytes to the induction of SCEs by mitomycin C (MMC) either in vitro (3 X 10(-8)/10(-7)M) or in vivo (0.3/3 mg/kg) . Since cordycepin is known to inhibit poly(A)synthesis thus blocking RNA maturation, it is suggested that M-MuLV proviral integration is not per se the sole factor responsible for the more pronounced susceptibility of BALB/Mo lymphocytes to SCE induction, but most likely viral gene expression and amplification are needed for this effect to occur. Drugs Exp Clin Res, 1985, 11(3), 195 - 9 Clinical study with cefoxitin in paediatrics; Rosaschino F et al.; A trial of cefoxitin was performed on 25 children needing urgent and accurate antibiotic therapy before laboratory test results could be made available . Cefoxitin proved to be highly active in the treatment of infections of bacterial origin . It was therefore found suitable for use in the clinical situation where the urgency of the need for treatment differs from theoretical practice. Drugs Exp Clin Res, 1985, 11(2), 123 - 5 Aclarubicin: experimental and clinical experience; Rothig HJ et al.; Aclarubicin, discovered by Umezawa in 1975, is a new cytostatic anthracycline antibiotic . It is one of the anthracyclines with the lowest cardiotoxicity, it is not mutagenic and it stimulates differentiation of tumour cells . The therapeutic index of aclarubicin (efficacy related to toxicity) is higher than that of doxorubicin and daunorubicin, using a proper dose schedule . Single dose therapy of aclarubicin shows only marginal efficacy, whereas multiple divided dose therapy exhibits efficacy comparable to that of doxorubicin and daunorubicin . Thus for clinical trials two dose schedules were designed: 25 mg/m2/day, days 1-7 for acute leukaemia; and 30 mg/m2/day, days 1-4 for solid tumours . Aclarubicin was shown to be highly active in acute leukaemia with 58% complete remissions in first relapse of AML . Good results were also seen in acute leukaemia in combination with cytosine arabinoside and thioguanine . In clinical trials with breast cancer and thyroid cancer the efficacy was in the same range as would be expected for doxorubicin, but side-effects were markedly reduced . Anorexia, mild nausea and infrequent vomiting were observed . Myelosuppression was common but dose reduction was not necessary . There was no alopecia and no congestive heart failure. Acta Chir Scand Suppl, 1985, 526, 129 - 37 High-dose corticosteroids in the critically ill patient . Current concept and future developments; Hinshaw LB; There are no generally accepted findings to support the use of corticosteroid in cardiogenic, hemorrhagic or septic shock in the human . Furthermore, there are concerns about the safety, appropriateness and practicality of the use of corticosteroids in severe sepsis/septic shock . There is, however, abundant evidence from animal studies that large doses of corticosteroid combined with antibiotic are extremely effective in preventing or reversing the pathophysiological and lethal manifestations of E . coli-induced shock . It is important to determine if this particular therapy has human application . Results from previous clinical studies evaluating the effectiveness of corticosteroid in severe sepsis/septic shock are in marked conflict . There is now an urgent need for carefully designed clinical studies to determine if there are human subgroup populations with severe sepsis who respond similarly to the animal who can be successfully treated with high dose corticosteroid combined with conventional therapy. Invest New Drugs, 1985, 3(4), 403 - 10 Echinomycin: the first bifunctional intercalating agent in clinical trials; Foster BJ et al.; Echinomycin is a quinoxaline antibiotic that was originally isolated from Streptomyces echinatus . Based on its antitumor activity against two i.p . implanted murine tumors, the B16 melanoma, and the P388 leukemia, it was brought into clinical trials by the National Cancer Institute . Recent studies on its cytotoxic action have related its antitumor activity with its ability to bifunctionally intercalate with double stranded DNA . Toxicologic studies were carried out in CDF1 mice and beagle dogs using intravenous injections . For the mice studies the dose ranges were 288-692 mcg/kg (864-2076 mcg/m2) by single bolus, and 112-254 mcg/kg/day (336-762 mcg/m2/day) for five consecutive days . In the dog, dose ranges studied were 8.9-89.4 mcg/kg (178-1788 mcg/m2) by single bolus, and 3.4-33.5 mcg/kg/day (68-670 mcg/m2/day) for five consecutive days . The major toxic effects were found in the gastrointestinal, hepatic, and lymphoreticular systems . These were reversible at all but the highest dose, in dogs that had been treated for five consecutive days . Phase I clinical trials using various intravenous schedules were sponsored by the National Cancer Institute . Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered . Based on results from these studies, the National Cancer Institute has recently begun phase II trials in a broad range of diseases . These trials will further characterize echinomycin's toxic effects and its antitumor activity. Vet Med Nauki, 1985, 22(7), 40 - 7 {Therapeutic aspects of coli mastitis in ruminants}; Verheijden JH et al.; Cows with coliform mastitis showed, in addition to fever, tachycardia and ruminal stasis and a concatenation of nonspecific responses, such as neutrophylic leukopenia followed by leukocytosis, lymphopenia, hypocalcaemia, hypoferraemia, hypozincaemia, and hypercupremia, and changes in the concentration of certain serum proteins . Similar responses occurred in cows and goats when mastitis was induced by an E . coli endotoxin or following the i/v injection of such endotoxin . Research suggested that in cows with clinical mastitis the symptoms of a generalized disease were predominantly the result of the release of phagocyte endogenous proteins at the site of inflammation in the mammary gland . Another inflammatory protein was the leukocytic endothelial mediator which changed the plasma concentrations of trace elements . Local treatment with the rather toxic antibiotic, polymyxin B, blocked the effect of the endotoxin administered via the udder on plasma Zn and Fe values . Therefore, local treatment with this drug seemed to be indicated with cows having E . coli mastitis . Based on pharmacokinetic behaviour parenteral treatment of such cows with trimethoprim or chloramphenicol appeared to be interest . Furthermore fluboprofen, a nonsteroid antiinflammatory agent was shown to possess a beneficial effect in cows with experimental E . coli mastitis. Ann Chir Gynaecol Suppl, 1985, 198, 76 - 80 Hip replacement arthroplasty in rheumatoid arthritis; Heywood AW; Numerous factors conspire to make hip replacement arthroplasty for rheumatoid arthritis different from the same operation in osteo-arthritis . Patients are frequently younger, arousing fears that the patient will outlive the prosthesis . However this factor is more than counterbalanced by the constraints imposed by the disease in other joints: polyarticular involvement usually protects the hip arthroplasty from weight-bearing stress thus prolonging its life . Protrusio acetabuli, uncommon in osteo-arthritis is the commonest presentation in rheumatoid arthritis because of the concentric cartilage degradation which erodes the acetabulum medially and proximally . In arthroplasty for protrusio, a plea is made for grafting of the floor of the acetabulum with solid bone derived usually from the femoral head . This offers a stronger and more physiological support for the acetabular component than synthetic devices . The hip is often only one of the many joints requiring arthroplasty to maintain locomotor function in severe cases of rheumatoid and the results of multiple operations are usually very gratifying . However, any form of surgery may be contra-indicated in a patient enfeebled by prolonged immobilisation from involvement of multiple joints . Late infection of cemented prosthesis is commoner in rheumatoid than in osteo-arthritis: such patients need antibiotic cover during transient bacteraemia from any cause such as dental extraction, trivial infections etc. Trans Ophthalmol Soc U K, 1985, 104 ( Pt 4), 402 - 9 The effects of topical drugs and preservatives on the tears and corneal epithelium in dry eye; Burstein NL; Medications used in 'Dry Eye' patients are reviewed for their effects on the corneal surface including the overlying tear film . Preservatives are discussed, since they affect the properties of commercial preparations which may be instilled frequently as a substitute for normal tears . The major beneficial effect which a topically applied agent can have on epithelium is to supplement or stabilise the tear film . Thimerosal sometimes triggers a sensitivity reaction, and other mercurial compounds are unstable . Benzalkonium chloride compromises both corneal epithelium and tear film . Some cationic detergents, including chlorhexidine digluconate and polyquat, cause less disruption at prophylactic concentrations . The use of a small drop size is helpful in preventing toxic effects of preservatives . All preservatives should be avoided when unit doses of a sterile tear replacement, such as saline, can be made available . Topical antibiotics should be used only to control known bacterial infections, avoiding high concentrations of bacitracin, gentamicin, and neomycin . Steroids and antibiotic/steroid combinations must be used with great caution, and only when uncontrolled ocular inflammation justifies the risk of possible corneal ulceration. Curr Med Res Opin, 1985, 9(8), 536 - 41 The management of elderly patients with acute lower respiratory tract infections: a comparison of pivampicillin and amoxycillin; Admani AK et al.; In a randomized trial, the efficacy of pivampicillin (500 mg or 1 g twice daily) was compared with that of amoxycillin (250 mg or 500 mg 3-times daily) in 43 elderly hospitalized patients with bronchopneumonia (32 patients) or an acute exacerbation of chronic bronchitis (11 patients) . Overall, 13 (57%) out of the 23 patients taking pivampicillin were cured, and the remaining 10 subjects were improved . In the amoxycillin group, there were 9 (45%) cures, 9 improved and 2 failures of treatment . One patient in each treatment group had mild side-effects . Forty (93%) out of the 43 patients in the study expressed a preference for an antibiotic that was given twice daily as opposed to one where 3 doses were taken each day. Urol Radiol, 1985, 7(2), 109 - 11 Ultrasound detection of focal bacterial nephritis (lobar nephronia) and its evolution into a renal abscess; McCoy RI et al.; A case of acute focal bacterial nephritis (lobar nephronia) which evolved into a renal abscess is reported . This case is unusual for 2 reasons: the focal nephritis was isoechoic (not previously reported), and it progressed to an abscess despite antibiotic therapy . Ultrasound initially detected the focal nephritis and later confirmed its progression to an abscess . Successful treatment was obtained with sonographically guided percutaneous catheter drainage in conjunction with systemic antibiotics. Circ Shock, 1985, 15(4), 261 - 80 Myocardial dysfunction in endotoxin- and E . coli-induced shock: pathophysiological mechanisms; Archer LT; Experimental studies have documented that myocardial dysfunction is precipitated between 3 and 6 hr after endotoxin or E . coli . This finding has now been confirmed in human septic shock . A "Hinshaw-modified" isolated working left ventricle preparation has been used to document and assess the degree of failure . It was found that the failure is often severe and reversible only temporarily by adrenergic agents but reversible by digoxin or insulin . The cause of the failure has not been identified, but evidence is presented against a myocardial depressant factor (MDF) being the causative factor . Hearts subjected to a 2-4 hr period of hypotension on the threshold of failure show no signs of failure when subjected to blood circulating from an animal in splanchnic arterial occlusion shock . Hearts from pancreatectomized animals subjected to endotoxin shock with their source of MDF removed demonstrate the typical failure in 4-6 hr . Other factors are suggested that contribute to myocardial dysfunction: hypotension or nonuniform perfusion of subendocardial regions of the heart, depressed responsiveness to inotropic and chronotropic stimuli, intracardiac ionic and fluid disturbances, and increases in heart chamber and muscle stiffness . Since steroid/antibiotic therapy increases the probability (p less than 0.05) that an animal will survive lethal sepsis, investigating the effect of this therapy on myocardial function may aid in determining whether or not this degree of heart failure contributes in the animal to irreversible shock and death. Antibiot Med Biotekhnol, 1985 Jan, 30(1), 47 - 50 {An immunoenzyme method of determining benzylpenicillin in biological substrates and its antibodies in immunized animals}; Vinogradova AL et al.; Lately it appeared to be necessary to develop-alternative methods for control of antibiotic therapy . Detection of low molecular substances based on the immunoenzymatic assay (IEA) is one of the most promising approaches to the development of such methods . The authors developed a quantitative method for determination of benzylpenicillin (BP) according to the procedure described earlier by Van Weemen . The BP antisera were prepared by immunization of rabbits with a conjugate of bovine serum albumin . The gamma-globulin fraction isolated from the antisera was conjugated with peroxidase . The working dilution of the conjugate was determined by the chess titration method . The test system of competitive binding developed by the authors provides detection of BP in the biological fluids in concentrations of 0.1 to 0.0001 microgram/ml (by BP dry weight). Invest New Drugs, 1985, 3(1), 3 - 21 The effectiveness of the anthracycline analog 4'-epidoxorubicin in the treatment of experimental tumors: a review; Goldin A et al.; The current report presents the data of the Division of Cancer Treatment of the National Cancer Institute (NCI) on the antitumor activity of the anthracycline antibiotic 4'-epidoxorubicin in experimental tumor systems . Direct comparisons are made with doxorubicin in individual experiments, and the data are related to those of earlier studies in the form of a review of experimental activity, in order to assess the relative activity of 4'-epidoxorubicin and doxorubicin . The experimental test models utilized by the NCI for these studies included the leukemias P388 and L1210, B-16 melanoma, Lewis lung carcinoma, the colon tumors 26 and 38, and the mammary tumors CD8F1 and C3H16/C . The human tumors growing in xenograft in athymic mice included the models LX-1 lung tumor, CX-1 colon tumor, and MX-1 mammary tumor . Additional comparisons were made with the tumor models Gross leukemia, sarcoma 180, MSV-induced sarcoma, MS-2 tumor, and a variety of human tumors growing in athymic mice, as well as with in vivo toxicologic and in vitro cytotoxicity models . Although for 4'-epidoxorubicin there is only a minimal alteration of the configuration of the doxorubicin molecule, quantitative comparison of 4'-epidoxorubicin and doxorubicin revealed not only similarities but also differences in biological activity . Both drugs showed activity against a broad spectrum of experimental tumors, with 4'-epidoxorubicin more effective against some tumors and equally effective against others . 4'-Epidoxorubicin evidenced less toxicity than doxorubicin in both acute and chronic toxicity studies with retention of therapeutic effectiveness and showed reduced cardiotoxicity . With 4'-epidoxorubicin there resulted a higher therapeutic index and therapeutic ratio, permitting the use of higher dosage and a greater margin of safety . The preclinical differences in therapeutic and toxicologic manifestations of 4'-epidoxorubicin, reflecting apparent alterations in pharmacologic properties and mode of action in comparison with doxorubicin, support the broad spectrum clinical trials of this already-demonstrated clinically active drug. Biosci Rep, 1985 Jan, 5(1), 29 - 37 Stable maintenance in chemostat-grown Escherichia coli of pBR322 and pACYC184 by disruption of the tetracycline resistance gene; Vernet T et al.; Plasmid stability was studied in antibiotic-free chemostat cultures . Disruption, either by deletion or insertion, of the tetracycline resistance gene in the EcoR1/EcoRV region of the cloning vector pBR322 or in the HindIII/BamH1 region of pACYC184 yields plasmids markedly more stable than the parent plasmids . Thus, at least for these two instances, cloning of a partitioning (par) locus is not prerequisite for plasmid maintenance. J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 1 - 6 The theory and relevance of continuous culture; Gilbert P; Batch cultures of micro-organisms which utilize typical laboratory media, generally result in rapidly dividing cultures (generation times less than 1 h) . These are atypical of those found in natural environments . The continuous culture of micro-organisms allows either specific-growth-rate to be controlled, whilst maintaining the cells in a constant physical and chemical environment or a constant specific-growth-rate to be maintained whilst physico-chemical parameters of growth such as pH, temperature or nutrient availability are varied . Continuous culture therefore offers the prospect of in-vitro culture of micro-organisms in physiological states relevant to their natural habitats . This article introduces the concepts of continuous culture and discusses their relevance towards in-vitro models of infection and of antibiotic dosing. Ann Emerg Med, 1985 Jan, 14(1), 15 - 9 Treatment of cutaneous abscess: a double-blind clinical study; Llera JL et al.; Controversy exists about the value of antibiotic therapy following incision and drainage of cutaneous abscess . We undertook a randomized double-blind study to clarify the controversy . Adult patients with cutaneous abscesses who received outpatient surgical therapy were entered into the study . Following incision and drainage, patients received cephradine or placebo for seven days using a randomized code in a double-blind fashion . At the end of seven days, patients were reevaluated . Twenty-seven patients were treated with cephradine, and 23 with placebo . Ninety-six percent of the patients in each group were improved clinically after seven days . We conclude that cephradine did not alter the outcome of cutaneous abscesses at one week after incision and drainage . The implications are twofold: patients are not exposed to the potential side effects and allergic reactions of antibiotics, and the cost of health care can be reduced by not prescribing antibiotics in these patients. J Immunol, 1985 Jan, 134(1), 423 - 30 Differential glycosylation requirements for the cell surface expression of class I molecules; Landolfi NF et al.; The importance of asparagine-linked glycosylation in the cell surface expression of several class I molecules was examined . C57BL/6 (B6) T cell blasts were treated with tunicamycin (TM), an antibiotic that inhibits N-linked glycosylation . The levels of various class I molecules on these cells were examined by flow cytometry and were compared to the levels of the same molecules on untreated cells . A 12-hr TM treatment did not significantly alter the levels of H-2Kb, Db, or Qa-2; however, such treatment decreased the surface expression of the Qa-1b allelic product to undetectable levels . A time-course study indicated that a decrease in the level of Qa-1.2 expression was apparent after only 4 hr of TM treatment . An examination of T cell blasts prepared from mouse strains possessing the Qa-1a, Qa-1c, and Qa-1d alleles indicated that all allelic products of this locus demonstrated a marked decrease in cell surface expression on TM treatment, whereas other class I molecules (H-2Ks, TL) exhibited slight or no decrease . Two-dimensional polyacrylamide gel electrophoresis analysis of immunoprecipitates from detergent lysates of surface-iodinated TM-treated B6 blasts revealed the presence of the unglycosylated form of the H-2Kb molecule on the cell surface . No such form of the Qa-1.2 molecule could be detected by similar analysis . To establish that the above observations were not simply a result of the inability of the Qa-1-specific alloantisera to react with the unglycosylated Qa-1 molecule, lysates of surface-iodinated B6 blasts were digested with endoglycosidase F, which cleaves N-linked carbohydrate moieties . Immunoprecipitation analysis indicated that the antisera could react with the unglycosylated form of the Qa-1 molecule . These results indicate that N-linked glycosylation has differential importance in the cell surface expression of class I molecules. Drugs Exp Clin Res, 1985, 11(4), 263 - 8 Clinical experience with miocamycin in the treatment of respiratory tract infections; Rimoldi R et al.; The object of the study was to evaluate the therapeutic effectiveness and tolerability of miocamycin, a new macrolide antibiotic, in 86 patients with lower respiratory tract infections . The mean peak concentration of miocamycin was determined in bronchial secretions . High concentrations were recorded, in some cases exceeding serum levels . The pathogens were eradicated in all cases, with few side-effects. Clin Invest Med, 1985, 8(2), 139 - 47 Nystatin prophylaxis of fungal colonization and infection in granulocytopenic patients: correlation of colonization and clinical outcome; Buchanan AG et al.; Nystatin, one million units every four hours, was prospectively studied as a prophylactic antifungal agent in 164 neutropenic patients who were not initially colonized by fungi: 104 received nystatin and 60 served as controls . Fungal colonization occurred in 68/104 (65%) nystatin recipients and in 43/60 (71%) controls . However, nystatin significantly reduced multiple body site colonization and persistent oropharyngeal colonization . Despite these alterations in colonization profile, 16/104 (15%) nystatin recipients developed disseminated fungal infections, as compared to 5/60 (8%) control patients (0.5 greater than p greater than 0.1, N.S) . Differences in the clinical course of colonized and non-colonized patients were observed . Eighteen of 111 (16%) colonized patients had afebrile clinical courses as compared to 16/53 (30%) non-colonized patients (p less than 0.05) . Twenty-nine of 93 (31%) febrile episodes in colonized patients failed to respond to empiric antibiotic therapy as compared to 3/37 (8%) episodes in non-colonized patients (p less than 0.01) . Disseminated fungal infections were diagnosed in 19/111 (17%) of colonized patients, as compared to 1/53 (2%) non-colonized patients (p less than 0.02) . We conclude that colonized patients are more likely to develop febrile clinical courses, to fail to respond to empiric antibiotic therapy, and to develop disseminated fungal infection . Nystatin altered colonization patterns but did not prevent disseminated fungal infection. Invest Ophthalmol Vis Sci, 1985 Jan, 26(1), 105 - 10 Biosynthetic human EGF accelerates healing of Neodecadron-treated primate corneas; Brightwell JR et al.; Topical administration of biosynthetic human epidermal growth factor (h-EGF), given in combination with an antibiotic and synthetic steroid (Neodecadron) accelerated the rate of corneal epithelial regeneration and significantly increased the strength of full-thickness stromal incisions in primates . The regenerated epithelial cells of EGF-Neodecadron-treated corneas appeared normal on histologic examination and showed no evidence of hypertrophy or hyperplasia . The EGF-Neodecadron-treated stromal incisions were characterized by new collagen formation and a smaller epithelial cell plug than Neodecadron-treated control corneas . These results suggest that biosynthetic h-EGF, which lacks the immunologic potential of nonhuman proteins, may be effective in accelerating healing of corneal epithelial defects and stromal incisions in patients whose healing is suppressed by treatment with steroids. Ophthalmologica, 1985, 191(1), 29 - 34 {Intraocular penetration of systemically administered cephalosporins under steady-state conditions in animal experiments}; Volker B et al.; In previous studies of intraocular penetration of systemically applied antibiotics a single dose of the antibiotic was applied . An experimental study was performed in order to determine if maintaining a constant serum level for an extended period of time will lead to an increase in ocular concentration . The antibiotic dosage was calculated so that the serum level remained constant for a given period of time . Using the rabbit as an experimental animal two cephalosporins (Cefsulodin, Cefotiam) were then injected intravenously using an infusion pump . Evaluation of serum levels (high-performance liquid chromatography) revealed constant levels for each animal but different interindividual levels . The intraocular concentrations of Cefsulodin and Cefotiam were different . The intraocular level of Cefsulodin rose continuously over a period of 5 h, whereas the Cefotiam levels remained at the concentration measured after bolus injection. J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 261 - 4 Simultaneous simulation of two different concentration time curves in vitro; Shah PM; A model for in-vitro simultaneous simulation of two different patterns of pharmacokinetic parameters was developed . In the first compartment the initial concentration simulates that seen after intravenous infusion or bolus injection and the antibiotic is diluted at a constant rate . In the second compartment the concentration rises from zero to a maximum of 1/4 the maximum of the first concentration . From this second compartment the drug is diluted at a slower rate. Oral Surg Oral Med Oral Pathol, 1985 Jan, 59(1), 28 - 33 Evaluation of treatment provided patients hospitalized with orofacial odontogenic infections: a retrospective study; Young EW et al.; The purpose of this study was to evaluate the treatment that patients receive when they are hospitalized for orofacial infections . Results indicated that dental consultations were not always obtained by medical personnel prior to the diagnosis and treatment of patients and that the antibiotic therapy employed did not always involve the recognized drug of choice. Ann Fr Anesth Reanim, 1985, 4(1), 77 - 8 {Bacterial meningitis and intrathecal treatment of chronic pain}; Ranchere JY et al.; A case is reported of bacterial meningitis related to an intradural implant used in the treatment of pain into which morphine was administered daily . The infection began on the third day after implantation of the system . Because of its efficiency in controlling pain, it was not removed; the infection was successfully treated with local and general antibiotic treatments only . The system was used 121 days. Surgery, 1985 Jan, 97(1), 93 - 6 Aortopulmonary fistula in a post-coarctation mycotic aneurysm; DaValle MJ et al.; A 21-year-old man presented with fever and septicemia resistant to antibiotic therapy . An unusual post-coarctation mycotic aortic aneurysm that had eroded into the left main stem bronchus was identified and replaced with a Dacron graft . A critical factor in achieving the satisfactory result was preparation of the femoral vessels for autotransfusion and possible cardiopulmonary bypass. J Emerg Med, 1985, 3(5), 345 - 51 Variability in the management of the febrile infant under 2 months of age; Berkowitz CD et al.; The management in the emergency department of febrile infants less than 2 months of age is influenced by the standard of practice in the community . We sought to determine if uniform practices existed across the United States . Individual academically based faculty from 154 (61%) United States pediatric residency programs responding to a questionnaire on the emergency department management of febrile infants less than 2 months of age showed great variability . Twenty-nine respondents reported written policies and 103 reported informal but defined guidelines for the evaluation and management of infants seen at their institutions . There was little consensus among the respondents as to the definition of fever in this age group . Those at institutions with formal policies reported using more laboratory tests in the evaluation . Respondents differed on the number and types of tests used and on antibiotic administration . University affiliation, type of population served, or presence of advanced training programs in ambulatory pediatrics were not related to the type of policy . The care of the young febrile infant varies greatly. Blood Cells, 1985, 11(2), 257 - 79 Comparison of performance for leukocyte differential counting of the Technicon H6000 system with a manual reference method using the NCCLS standard; Breakell ES et al.; The National Committee for Clinical Laboratory Standards (NCCLS) has published a tentative standard for leukocyte differential counting, by means of which a manual or automated method for leukocyte differential counting can be compared with a manual reference method . The performance of the Technicon H6000 system was evaluated using the standard at Stamford and Overlook Hospitals . A total of 502 patient samples were analyzed: 315 from Overlook and 187 from Stamford . The H6000 system was found to be approximately four times more precise than the 200-cell manual reference method for each cell type . Correlation of the H6000 system with the manual method was good, with correlation coefficients of 0.98 for neutrophils and lymphocytes, 0.96 for eosinophils, 0.72 for monocytes, and 0.5 for basophils . The clinical sensitivity of the H6000 system, measured in terms of false normals and false abnormals, was similar to that of the manual reference method when measured against itself . There were no clinically significant discrepancies in results from the H6000 system, except for possibly one case where a patient was already on antibiotic therapy . The NCCLS standard was found to be a useful but rather complex and involved method for evaluating the performance of the H6000 system, the major problem being the amount of work needed to count manually the number of cells required for the manual reference method.
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