Rev Pneumol Clin, 1986, 42(4), 207 - 13 {Immunotherapy of recurrent respiratory infections . Double-blind study of a new immunomodulator in 60 patients}; Germouty J; A new immunomodulator, SLO4 oral drops, was tested for treatment and prevention of recurrent respiratory infections in a double-blind, drug versus placebo trial conducted in 60 adults with chronic bronchitis or asthma . This agent brought about a highly significant reduction in the frequency and duration of infectious episodes, as well as a decrease in antibiotic consumption and lost work time . Well tolerated from the clinical and laboratory points of view, it proved remarkably effective . It has been hypothesized that induction of interferon may account for the excellent clinical results obtained with SLO4, and numerous authors regard this compound as one of the basic keys to regulation of immune reactivity . Pharmacological trials under way with SLO4 should help answer this question. Biotechnol Genet Eng Rev, 1986, 4, 59 - 78 DNA amplification and genetic instability in Streptomyces; Cullum J et al.; Genetic instability is very common in Streptomyces species, but only affects specific genes in any one strain . It sometimes occurs at high frequency spontaneously, but may be stimulated by treatments such as UV irradiation or intercalating agents . Deletion of genes occurs and may be accompanied by DNA amplifications . It is unlikely that there is plasmid involvement in most cases . Little is yet known about the molecular mechanisms of deletion and DNA amplification . Genetic instability can be a problem during commercial antibiotic production . DNA amplification of cloned genes is potentially useful for achieving both stability and high gene dosage. East Afr Med J, 1986 Jan, 63(1), 29 - 35 Enterotoxigenic Escherichia coli infection in childhood diarrhoea in Mombasa, Kenya; Waiyaki PG et al.; PIP: This study was carried out at the Coast General Hospital in Mombasa, Kenya, during the dry month of March, 1984 . Stool specimens were collected from 81 infants and children aged 0-36 months and with diarrhea of less than 7 days' duration . 35 age-matched children, who visited the hospitals with complaints other than gastrointestinal, served as controls . None of the children had received previous antibiotic therapy . Stools were checked for enterotoxigenic Escherichia coli (ETEC) . E . coli isolates were assayed for labile toxin (LT) and stable toxin (ST) production by the Biken test and the suckling mouse assay, respectively . 19 ETEC were isolated from children with diarrhea, constituting an isolation rate of 23.5% . No ETEC were isolated from the controls . ST producers predominated (94.7%) . Results indicate that the rates of ETEC isolation increase with age . In the majority of cases (16/19) ETEC caused diarrhea which was watery, with the number of motions ranging from 3 to 10 times . Fever was present in 9 patients . Mucus and blood were observed in very few cases . Vomiting was frequent (10/19) but abdominal pain was less common (5/10) . Mycopathologia, 1986 Jan, 93(1), 13 - 4 Antemortem diagnosis of an apparent case of feline candidiasis; Lorenzini R et al.; Candidiasis in cats has always been linked with such predisposing factors as parvovirus infections and antibiotic and chemotherapeutic treatments . Moreover these cases were all diagnosed post-mortem . The clinical observations and the diagnostic procedures used in an antemortem case of probable idiopathic intestinal candidiasis in a cat are reported . The therapeutic measures used and the method of evaluating the efficacy of antimycotic treatment are also described. Mutat Res, 1986 Jan, 173(1), 25 - 9 Sensitivity of DNA-repair-deficient strains of Escherichia coli to rifampicin killing; Chao L; We have analyzed the role of RNA polymerase in DNA repair using the antibiotic rifampicin which binds specifically to the beta subunit of the enzyme . Several DNA-repair-deficient strains such as recA, uvr, and polA, and their isogenic parents were used for this study . All repair-deficient strains were found to be hypersensitive to rifampicin killing . Compared to the isogenic parent strains, recA strains are about 50 times more sensitive and the polA strain is about 100 times more sensitive to rifampicin killing . UvrA and uvrB strains are slightly more sensitive to rifampicin than the wild-type strains . The hypersensitivity of repair-deficient strains to rifampicin killing is totally abolished by the introduction of rifampicin-resistant mutations into these strains . We have examined the effect of rifampicin on RNA and protein synthesis in repair-deficient and -proficient strains . RNA and protein synthesis were found to be inhibited by rifampicin to the same extent among all the strains tested . The results also show that the resumption of DNA synthesis was significantly disrupted in DNA-repair-deficient strains following drug removal . Taken together these results suggest that RNA polymerase plays an essential role in DNA metabolism and such function may be replaced by polA and recA gene products and to a lesser extend by uvrA and uvrB gene products. J Fam Pract, 1986 Jan, 22(1), 39 - 43 Are antihistamine-decongestants of value in the treatment of acute otitis media in children? Schnore SK, Sangster JF, Gerace TM, Bass MJ. Acute otitis media is the most common bacterial infection of childhood . The effectiveness of oral antihistamine-decongestant mixtures in the treatment of this illness remains controversial in clinical practice . In a double-blind randomized study, 82 children (aged under 15 years) with acute otitis media were treated with amoxicillin and either a decongestant-antihistamine mixture (Dimetapp) or placebo . All diagnoses required agreement between a family practice resident and the supervising family physician . Clinical course was assessed by symptom diaries completed by parents and by follow-up examination at approximately two weeks, which included pneumatic otoscopy . No statistically significant benefit of the antihistamine-decongestant mixture was shown in terms of resolution of the symptoms or prevention of the complications of acute otitis media . It is recommended that antihistamine-decongestants not be routinely added to an antibiotic in the treatment of acute otitis media in children. Drugs, 1986, 32 Suppl 3, 50 - 6 A comparative study of cefadroxil and co-trimoxazole in patients with lower respiratory tract infections; Castro M; The most common causative pathogens in lower respiratory disease are S . pneumoniae, H . influenzae and S . pyogenes . Cefadroxil and co-trimoxazole, both orally administered broad spectrum antibiotics, are effective against these organisms when given in a twice-daily regimen . In this open randomised study, 42 patients with lower respiratory tract infections received cefadroxil 1 g or co-trimoxazole 1 double-strength tablet every 12 hours for a mean duration of 11 and 13 days, respectively . Pathogens were isolated in the pre-treatment sputum of 51% of patients given cefadroxil and in 25% of those who received co-trimoxazole . Similar overall cure rates were observed after treatment with cefadroxil (67%) and co-trimoxazole (60%); sputum purulence was similarly diminished by both drugs (91% and 85%, respectively) . Neither antibiotic caused serious side effects . Thus, in a convenient twice-daily regimen, cefadroxil and co-trimoxazole are comparably effective in treating lower respiratory tract infections. Vox Sang, 1986, 51 Suppl 2, 63 - 8 Treatment of AB deficiencies; Cunningham-Rundles C; The objective of this study was to compare serum immunoglobulin levels and the clinical status of patients with primary immune deficiency who received an intravenous immunoglobulin (IVIG) (pH 4.0) preparation for 1 year with results previously obtained when the same patients received intramuscular immunoglobulin (IMIG) . During the IVIG treatment year, increased serum immunoglobulin levels, shorter duration of certain infectious disorders, reduced antibiotic use, ans improved rheumatoid symptoms were observed . The actual benefit of IVIG therapy could not be established until after the sixth months, since illness was even further reduced during the second 6 months of treatment . Other clinical observations are evaluated in the 2 groups. Infection, 1986, 14 Suppl 4, S274 - 5 Ofloxacin: concentration in human ejaculate and influence on sperm motility; Schramm P; The concentration of ofloxacin was measured in both fractions of split-ejaculate from five volunteers treated with ofloxacin 400 mg/day for 3.5 consecutive days . Concentrations in both fractions were equal, 2.44 mg/l and 2.5 mg/l, respectively indicating that the penetration of ofloxacin into the prostate gland and into the vesical glands are of the same magnitude . Sperm motility was not affected by ofloxacin in a concentration of 4.5 mg/l as tested on fresh ejaculate of 29 andrologic patients . Thus ofloxacin proves to be useful as a potent antibiotic in clinical care for andrologic patients. Arch Oral Biol, 1986, 31(8), 549 - 54 A freeze-fracture cytochemical study of filipin-sterol complexes in pulp fibroblasts of the rat incisor; Cho MI et al.; The sterols in microdomains of the cell membrane of pulp fibroblasts react with the polyene antibiotic, filipin, to form filipin-sterol complexes (FSC) . The FSC appear in ultra-thin sections as minute corrugations or deformations of the membrane . In freeze-fracture replicas, individual FSC were 20-30 nm elevations and were abundant on filopodial cell processes . They were not found in the membrane of cell-to-matrix attachment plaques or in cell-to-cell adherens junctions . The findings suggest that stabilization of the membrane at these sites may interfere with FSC formation and conversely that the absence of FSC may be an indication of membrane stabilization. Cancer Chemother Pharmacol, 1986, 18(2), 153 - 6 Preclinical evaluation of aclacinomycin A for the intraperitoneal treatment of human ovarian carcinoma; Louie KG et al.; Combination chemotherapy regimens have produced a pathological complete response rate of only 1%-25% in patients with advanced ovarian cancer . Patients with small-volume residual disease after treatment are refractory to further systemic therapy, and most eventually die of their disease . Intraperitoneal (i.p.) chemotherapy, particularly with adriamycin or cisplatin has shown promise in these patients . However, the dose-limiting painful peritonitis associated with i.p . adriamycin makes this regimen potentially too toxic for many patients . Aclacinomycin A, another anthracycline antibiotic, has been found to have activity against a wide variety of murine tumors and human xenografts . It has also demonstrated clinical efficacy in phase I and II trials against refractory ovarian cancer and has less pronounced vesicant properties than adriamycin, making it an ideal candidate for i.p . use in ovarian cancer patients . In vitro clonogenic assays utilizing a battery of adriamycin-sensitive and -resistant human ovarian carcinoma cell lines have shown that aclacinomycin A is more cytotoxic than adriamycin in all cell lines tested . In addition, aclacinomycin A was found to prolong survival in a nude mouse xenograft of i.p . human ovarian cancer . These results have provided the experimental rationale for an ongoing clinical trial of i.p . aclacinomycin in refractory ovarian cancer patients at the Medicine Branch, NCI. Ter Arkh, 1986, 58(9), 141 - 4 {Extramedullary manifestations of blast crisis in chronic myeloleukemia}; Volkova MA et al.; The paper is concerned with the development of extramedullary blast infiltrates in Ph-positive chronic myeloid leukemia . Two cases are described . In one case during the blastic phase lasting 27 months, a female patient developed by turn skin leukemids, lesions of the soft tissues in the knee joint, lesions of the stomach, lungs and heart . Administration of the treatment according to the "3 + 7" scheme (an anthracycline antibiotic plus cytosar) and to the TRAMPCOL scheme brought about the reverse development of the infiltrates . In the second case a male patient in the 12th year of the disease developed, in the absence of the blastic phase, massive blast lesions of the lymph nodes of the mediastinum followed by neuroleukemia . The lesions were removed by the treatment according to the ACOP scheme and endolumbal injections of methotrexate and cytosar . Ten months after diagnosing the enlargement of the lymph nodes of the mediastinum the picture of the blood and the bone marrow remained typical of the marked stage of the disease . The authors provide brief data on 27 patients with extramedullary blast infiltrates in the terminal stage of chronic myeloid leukemia together with short reported data. Chemotherapy, 1986, 32(5), 404 - 7 Penetration of N-formimidoyl thienamycin into extravascular fluids in rabbits; Olay T et al.; The penetration of N-formimidoyl thienamycin into extravascular fluids was studied in rabbits . Two different models were used: subcutaneously implanted tissue chambers and fibrin clots . The antibiotic was given intramuscularly as a single dose of 10 mg/kg . The degree of penetration into these compartments was determined by comparing the area under the curve for the specific fluid with the area under the curve for plasma expressed in percent . The percentage of penetration of N-formimidoyl thienamycin into tissue chamber fluid (76.24%) was similar to that into fibrin clots (75.15%). Int Surg, 1986 Jan-Mar, 71(1), 14 - 7 Peri-incisional and preoperative administration of cefmetazole for the prophylaxis of wound infection after appendicectomy; Garcia Garcia J et al.; The tissue and blood levels of Cefmetazole are compared after preoperative administration of a single dose of 30 mg/K body weight of the antibiotic administered intravenously (15 patients) and peri-incisionally (30 patients) to patients scheduled for emergency appendicectomy . Local and general tolerance to the antibiotic was good by both routes . No local or general complications arose in any of the patients . As expected, the tissue concentrations achieved with peri-incisional infiltration were significantly higher than those obtained by the intravenous route . With the blood levels, exactly the opposite happens at the start of the operation whereas at the end, there were no significant differences between the two routes employed . The prophylactic administration by peri-incisional infiltration is an easy and safe method which provides high tissue concentrations simultaneously with adequate blood levels and should be considered as useful in the preoperative administration of antibiotics for prophylaxis. Invest New Drugs, 1986, 4(1), 31 - 8 Phase I study of oral idarubicin given with a weekly schedule; Dodion P et al.; Thirty one patients with solid tumors were entered into a phase I trial with idarubicin, a new anthracycline antibiotic with oral antitumor activity in animals . The drug was scheduled to be given for 4 consecutive weeks at doses ranging from 10 to 20 mg/m2 . Leukopenia was the dose-limiting toxicity . Thrombocytopenia was occasionally seen . Since several patients could not receive the third and fourth administrations of the drug at 17.5 and 20 mg/m2, higher doses were administered only for 2 consecutive weeks . With this schedule, the maximum tolerated dose was 25 mg/m2 and leukopenia was again the dose-limiting toxicity . With both schedules, myelosuppression was highly variable and could not be related to prior therapy, bone or liver metastases, or performance status . Other toxicities were mild to moderate and were dominated by nausea and vomiting which were observed in 29% of the patients . Alopecia and mucositis were unfrequent and cardiac toxicity was not observed . Starting doses of 15 mg/m2 for 4 consecutive weeks or 20 mg/m2 for 2 consecutive weeks could be proposed for oral phase II studies with idarubicin, under careful pharmacokinetic monitoring. Ophthal Plast Reconstr Surg, 1986, 2(4), 209 - 11 Dacryocystitis following Kawasaki's disease; Mauriello JA Jr et al.; A 6 1/2-year-old white male child had developed bilateral dacryocystitis 1 year earlier, approximately 6 months after resolution of the acute phase of Kawasaki's disease . The patient had had no previous history of dacryostenosis or epiphora . After he failed to respond to appropriate antibiotic therapy, probing was partially successful on the right side, but complete obstruction persisted on the left side . At age 7 1/2 years, dacryocystorhinostomy was performed successfully on the left side . To our knowledge, dacryocystitis has not been reported previously following Kawasaki's disease . Other reported ocular complications of Kawasaki's disease, with the exception of a case of bilateral conjunctival scarring, have occurred in the acute phase of the disease. Ophthal Plast Reconstr Surg, 1986, 2(1), 15 - 9 Osteomyelitis of the orbit . A case report; Townsend DJ et al.; With the advent of the antibiotic era, the incidence of osteomyelitis has decreased remarkably . However, cases of trauma-induced orbital cellulitis, abscess, fistula formation, and osteomyelitis may still occur . The following case is illustrative of the chronicity of problems (8-year course) caused by retained orbital wooden foreign bodies. Psychopharmacology (Berl), 1986, 90(3), 347 - 50 New approaches to postmarketing surveillance; Fisher S et al.; As part of a large-scale ongoing project exploring new pharmacy-based methods of postmarketing surveillance, we are comparing a patient-initiated monitoring system to a staff-initiated approach . Here we report data only from staff-initiated, computer-directed telephone interviews with 231 outpatients approximately 2 weeks after they had been prescribed a target drug chosen from two markedly different pharmacological classes for which adverse drug reactions (ADRs) are well-documented . Our results indicate that spontaneous patient reports of "new or unusual symptoms" obtained from a standardized staff-initiated telephone interview can be quite reliable, leading to accurate detection of known tricyclic antidepressant and antibiotic ADRs. Infection, 1986 Jan-Feb, 14(1), 27 - 31 Alteration of hemostasis associated with cefoperazone treatment; Andrassy K et al.; 21 Patients with normal and impaired renal function were given cefoperazone in a recommended dose of 4 g/day, irrespective of renal function . Platelet function and plasmatic coagulation were analyzed before and on day 7 of therapy . In patients with normal renal function on their usual diets, there was neither impairment of platelet function nor plasmatic coagulation . High serum antibiotic trough levels, prolongation of bleeding time and decreased vitamin K-dependent coagulation factors, as verified by the prolongation of prothrombin time and the appearance of descarboxyprothrombin, could be observed in those patients with impaired renal function whose insufficiency was far advanced and accompanied by a complex clinical picture . In this situation vitamin K deficiency may be due to poor oral intake, along with interference of hepatic vitamin K metabolism, showing an effect similar to that seen after coumarin therapy . Dosage reduction of the antibiotic in advanced renal failure and repeated control of prothrombin time is advised. Prostaglandins, 1986 Jan, 31(1), 83 - 93 Intestinal absorption in the mechanically obstructed rat intestine: protection by prostaglandins; Hajjar JJ et al.; Intestinal obstruction inhibits amino acid absorption . The inhibition, being dependent on the pathological changes of the absorptive epithelium, was considered as an index of injury and measured after varying periods of obstruction and after pretreatment with clindamycin, indomethacin, 16,16-dimethyl-PGE2 or arachidonic acid . A reduction in amino acid uptake was apparent after 2h of obstruction and was increasingly evident after 4, 6 and 18 h . During the late phase (after 6 h), inhibition was partly prevented by pretreatment with clindamycin, but the antibiotic was ineffective during the early phase (within the first 2 h) . Bacterial colony counts of luminal contents of rats obstructed for 2 h, were not different from counts obtained in controls, but significantly lower than counts in rats that have been obstructed for 6 h . Pretreatment of rats with 16,16-dimethyl-PGE2 or with arachidonic acid prevented the early inhibitory effects of the obstruction . The findings suggest that the early inhibition in amino acid uptake may be related to metabolic changes that are correctable by the administration of 16,16-dimethyl-PGE2 or of arachidonic acid . The inhibition, during the late phase, is mainly related to an overgrowth of the enteric bacteria. Pflugers Arch, 1986 Jan, 406(1), 6 - 11 Effects of a phorbol ester and diacylglycerols on secretion of mucin and arginine esterase by rat submandibular gland cells; Fleming N et al.; The effects of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and a diacylglyceride, 1-oleoyl-2-acetyl-glycerol (OAG) on the secretion of two major exocrine products by dispersed rat submandibular cells were investigated . TPA stimulated the release of acinar cell mucin and ductal cell protease (arginine esterase) in a dose- and time-dependent manner . Mucin secretion was also provoked by OAG, which, however, had no effect on arginine esterase release . The unsaturated diacylglycerol, 1,2-diolein, elicited a greater mucosecretory response than did OAG at the same concentration, while the saturated 1,2-distearin produced a smaller response . Mucin and enzyme secretion caused by TPA or OAG in the rat submandibular model was not inhibited by either of two putative antagonists, the antipsychotic drug, fluphenazine, and the antibiotic, polymyxin B . The involvement of extracellular Ca2+ in TPA-induced secretion was examined by comparing responses of cells maintained in normal or Ca2+-free medium, or in medium containing the ionophore A23187 . Although extracellular Ca2+ was not an absolute requirement for a secretory response, the results indicate a synergistic relationship between TPA and Ca2+ in stimulating the release of both mucin and arginine esterase . These results suggest a role for the Ca2+-, phospholipid-dependent enzyme, protein kinase C in the secretory mechanism of mucous and serous cells in the submandibular gland . This is consistent with the proposal that receptor-mediated hydrolysis of membrane phosphoinositides is an initial event in stimulus-response coupling in exocrine cells. Ann Surg, 1986 Jan, 203(1), 69 - 76 Perforation of the colon in renal homograft recipients . A report of 11 cases and a review of the literature; Church JM et al.; Colon perforation in renal transplant recipients is a potentially lethal condition that is amenable to appropriate medical and surgical treatment . The 11 cases seen at the Cleveland Clinic (incidence 1.1% of all renal transplant patients) and previous reports in the literature have been reviewed . The pathogenesis is related to a high incidence of diverticular disease in patients with polycystic kidneys and/or chronic renal failure, the effects of long-term immunosuppression, and the transplant procedure itself . The high mortality of this condition (61% overall) is related to the effects of immunosuppression on the response to sepsis and the surgical procedure used . Mortality has fallen from 88% (1970-1974) to 53% (1975-1979), and there are indications that it is continuing to fall . All four cases operated on here since 1980 have survived, giving a total operative mortality of 2/6, and all have maintained excellent allograft function . A high clinical index of suspicion, prompt exteriorization of the perforated colon, reduction of immunosuppression to minimal levels, and effective antibiotic coverage have all contributed to the declining mortality. J Basic Microbiol, 1986, 26(6), 323 - 8 Self-resistance of the nourseothricin-producing strain Streptomyces noursei; Haupt I et al.; The nourseothricin producer Streptomyces noursei is resistant to its own antibiotic in submerged as well as in surface culture . The strain shows no cross-resistance to miscoding inducing aminoglycoside antibiotics . Cell free extracts of Streptomyces noursei inactivate nourseothricin by enzymatic acetylation . The pattern of cross-resistance of Streptomyces noursei correlates well with the substrate specificity of the nourseothricin acetyltransferase . Furthermore, the acetyltransferase activity parallels the resistance level in nourseothricin-producing strains and nonproducing mutants . The results suggest that the nourseothricin acetyltransferase is important in the self-defence strategy of the nourseothricin-producing strain. Histochemistry, 1986, 85(3), 255 - 8 The effects of mucus on the binding of cationized ferritin by human and animal gastrointestinal epithelium; Sturrock N et al.; Human gallbladder and gastric epithelial cells are normally covered with a layer of mucus . When specimens were exposed to cationized ferritin (CF) in vitro, they did not regularly bind nor internalise it . If the tissues were first exposed to the mucolytic agents cysteamine or pepsin, then the gallbladder epithelium readily bound CF and the gastric epithelium irregularly . The in vivo binding of CF by guinea pig gallbladder could be abolished by the induction of mucous hypersecretion by the antibiotic lincomycin . The removal of the mucus by mucolytic agents restored the binding of CF . The irregular binding of CF by gastric mucosa after the use of mucolytic agents suggests other factors may be at play. Intervirology, 1986, 25(2), 61 - 8 VC11: an actinophage virulent to Streptomyces cattleya and Streptomyces olivaceus; Coyne VE et al.; Five soil samples were screened for the presence of a virulent actinophage . Phage VC11 was found to be virulent on Streptomyces olivaceus, S . cattleya, S . chartreusis, S . griseus (all important beta-lactam antibiotic producers), S . ambofaciens, S . parvulus, S . alboflavus, S . aureofaciens, and S . lividans TC10 . Although restriction-modification systems have been observed in S . olivaceus and S . cattleya, the phage EOP on these hosts remained relatively constant, indicating that these systems do not affect VC11. Jpn J Antibiot, 1986 Jan, 39(1), 87 - 93 {Therapeutic effect of ceftizoxime on infection in patients with lung cancer}; Hiraki S et al.; Ceftizoxime (CZX) was given in daily doses of 4 approximately 6 g by intravenous drip infusion to 30 patients with infection accompanying lung cancer to investigate the usefulness of the drug for infectious disease: The rate of effectiveness (marked and moderate) was 73.3% (22/30 patients) . Of the 30 patients, 2 had drug fever; 1, arthralgia; and 1, eosinophilia . These side effects improved after the drug was withdrawn . CZX is a very useful antibiotic with high effectiveness and safety in immunocompromised patients with infection accompanying advanced lung cancer. Antiviral Res, 1986 Jan, 6(1), 19 - 32 On the complex nature of the antiviral activity of coumermycin A1: its interference with the replication of herpes simplex virus type 1; Palu G et al.; The mechanism of inhibition of the replication of herpes simplex virus type 1 (HSV-1) by coumermycin A1 (CA1), an inhibitor of bacterial DNA gyrase, has been investigated . Concentrations of antibiotic slightly higher than those needed for 50% inhibition of viral growth were able to inhibit viral DNA synthesis in infected cells . This effect was accompanied by a depressed synthesis of viral polypeptides . Protein synthesis was also inhibited in uninfected cells, especially after long exposure to the drug, but not in a cell-free system . In vitro assays of highly purified HSV-1 DNA polymerase in the presence of the drug, provided evidence that the enzyme was a target of CA1 . The viral polymerase was in fact inhibited by the antibiotic to an extent comparable to that of viral DNA synthesis in intact cells . In contrast, DNA polymerase alpha, the enzyme involved in chromosomal DNA replication, was relatively insensitive to CA1 . The drug was also shown to bind to protein and to viral and cellular DNA. Mol Pharmacol, 1986 Jan, 29(1), 16 - 22 Expression of beta-adrenergic receptors in synchronous and asynchronous S49 lymphoma cells . II . Relationship between receptor number and response; Mahan LC et al.; We have used two experimental approaches--receptor inactivation with an irreversible antagonist and changes in receptor expression during passage of cells through the cell cycle--to explore the relationship between beta-adrenergic receptor number and response in intact S49 lymphoma cells . beta-Receptors in asynchronous cultures of S49 cells were blocked to varying degrees with the irreversible antagonist bromoacetylalprenololmenthane (BAAM) . Blockade by BAAM was noncompetitive and did not alter the affinity of receptors for the agonist isoproterenol . Intracellular accumulation of cAMP in response to 1 microM isoproterenol was proportional to receptor number both at times of initial and maximal accumulation . In contrast, when intracellular accumulation of cAMP in response to isoproterenol was measured in synchronized cultures of S49 cells (obtained by centrifugal elutriation), a notably different relationship was observed . Cells were least responsive, that is, receptors appeared "uncoupled," during S phase of the cell cycle . This attenuation of response was not due to alterations of receptor number, receptor affinity for agonist, or expression of the catalytic unit of adenylate cyclase . Use of the antibiotic mycophenolic acid, a selective inhibitor of the synthesis of GTP, elicited response patterns in asynchronous cells similar to those seen in synchronized cells . These results confirm that wild-type S49 cells do not possess spare receptors . In addition to the importance of total receptor number in determining maximal response to isoproterenol, receptors may show differential efficacy in promoting cAMP accumulation as cells traverse the cell cycle . Changes in cellular levels or utilization of GTP during the cell cycle may serve to regulate the coupling of receptors to the stimulation of adenylate cyclase. Microbiologica, 1986 Jan, 9(1), 89 - 93 Use of phage lambda CI857AprTcrN derivative for isolation of prophage-free cells; Slavchenko IYu et al.; A method for obtaining nonlysogenic bacteria from wild-type phage lysogenized strains using phage lambda with AprTcr markers and double amber-mutation in N gene is proposed . When the lysogenic culture is infected with antibiotic-resistant phage, the nonlysogenic cells present in the population are lysogenized and isolated on selective medium with Ap and Tc . Subsequent culturing of lysogenized cells on media without antibiotics leads to phage elimination due to its instability. Int J Biochem, 1986, 18(9), 821 - 7 Influence of streptozotocin upon the induction of tyrosine aminotransferase, the content of NAD and of 5-methyl cytosine in rat liver; Kroger H et al.; The antibiotic, streptozotocin, has carcinostatic, carcinogenic, and diabetogenic properties . Moreover, it is capable of inducing the enzyme tyrosine aminotransferase in a permanent line of rat liver cells . In the present publication, the effects of streptozotocin upon the induction of tyrosine aminotransferase, NAD synthesis, and methylation of DNA in different organs were analyzed in vivo . If administered alone, streptozotocin slightly induced tyrosine aminotransferase . The induction of tyrosine aminotransferase caused by tryptophan or nicotinamide was inhibited by streptozotocin . Streptozotocin reduced the NAD content of the liver . NAD synthesis induced by tryptophan was reduced by streptozotocin, while that induced by nicotinamide was enhanced . DNA methylation in the form of 5-methyl cytosine was not influenced by streptozotocin. J Hosp Infect, 1986 Jan, 7(1), 13 - 20 An outbreak of candidiasis in a special care baby unit: the use of a resistogram typing method; Phelps M et al.; An outbreak of candida infections involving 12 neonates in a special care baby unit is reported . An investigation of colonization of all the babies in the unit was made together with the sampling of the environment and hands of staff . Resistogram typing of isolates indicated the presence of several strains with probable cross-infection . Transmission was possibly by the hands of staff, but multiple antibiotic therapy may have played a role in the increased incidence of infection in the unit. Acta Microbiol Pol, 1986, 35(3-4), 251 - 7 Biosynthesis of cephamycin by resting cells of Streptomyces lactamdurans L 2/6; Chmiel A et al.; In order to investigate the nutritional conditions of cephamycin biosynthesis independently of the biomass growth process, the nutrient limited-resting cell system was used . A replacement medium eliminating cell multiplication was developed . The presence of Mg2+, carbon source and nitrogen source was necessary for cephamycin production by resting cells of Streptomyces lactamdurans L 2/6 . Maximum antibiotic production was obtained when maltose, saccharose, and fructose were used as carbon source, and L-asparagine as nitrogen source . An inhibitory effect on the process was exerted by the calcium ions . There was no visible inhibition of cephamycin biosynthesis by inorganic phosphate ions in concentration up to 100 mM. Folia Haematol Int Mag Klin Morphol Blutforsch, 1986, 113(5), 670 - 84 A critical evaluation of the available methods for the determination of factor VIII von Willebrand; Casonato A et al.; Von Willebrand factor (vWf) is the major component of the circulating factor VIII complex . The von Willebrand molecule includes factor VIII related antigen (VIIIR: Ag) which represents the molecular substrate of the von Willebrand activity expressed as Ristocetin cofactor (VIIIR:RCoF) activity . Several methods have been developed for VIIIR: Ag evaluation, among the first being the rocket-immunoelectrophoresis method of LAURELL . Radial immunodiffusion (MANCINI's method) was also used . Subsequently, radioimmunological assays, either as radioimmunoassay (RIA) or immunoradiometric assay (IRMA), were developed with improvements in sensitivity, so that levels of VIIIR: Ag lower than 0.1% of normal can be detected . More recently, an enzyme-linked immunosorbent assay (ELISA), characterized by the use of enzyme-conjugated antibody was proposed . This method shows a sensitivity similar to immunoradiometric methods but without using any dangerous reagent . Finally, a nephelometric method was proposed for factor VIII antigen evaluation . For a qualitative evaluation of von Willebrand factor crossed-immunoelectrophoresis and multimeric analysis can be used . In the first case, the use of precipiting antibodies against von Willebrand factor may demonstrate a peak with different characteristics related to the biochemical property of von Willebrand . Multimeric analysis in SDS-agarose gel electrophoresis followed by staining with labelled antifactor VIII antibodies gives information about different polymeric forms of circulating VIII/vW factor . Von Willebrand factor activity, expressed as its ability to induce platelet aggregation in the presence of the antibiotic Ristocetin, can be carried out using normal formalin fixed platelets, either with aggregometer or visual methods (glass slide test or tubes test and microtritation plate) . The corrected evaluation of factor VIII complex by all these techniques together with the clotting activity assay allows a satisfactory study of factor VIII properties. Drugs Exp Clin Res, 1986, 12(6-7), 441 - 53 Overview of the interaction between chemotherapeutic agents and DNA; Waring MJ; Some chemotherapeutic agents, such as the antibiotics mitomycin and bleomycin, modify the structure of DNA by chemical reactions involving the formation or breakage of covalent bonds . Others interact with the macromolecule reversibly to form a transient complex which may be intercalative or nonintercalative in character . Techniques are available to probe the extent of perturbation of DNA structure produced by these drugs, and they reveal subtle differences between the effects of various ligands . In recent years bifunctional intercalating agents such as the quinoxaline antibiotics have been discovered; their binding to DNA is often tighter than seen with simple (monofunctional) intercalators and there is evidence for nucleotide sequence-selectivity . Footprinting experiments have been employed to identify preferred ligand-binding sites in natural DNA fragments (CpG sequences in the case of echinomycin) and have revealed that local perturbations of the helical structure can be propagated into DNA regions flanking the antibiotic-binding sites . Crystallographic evidence suggests that echinomycin and its congeners recognise GC base-pairs by hydrogen bonding between the carbonyl groups of alanine residues in the antibiotic and the 2-amino groups of guanine nucleotides in the minor groove of the DNA helix . Kinetic studies support the hypothesis that sequence-selective antibiotic molecules "shuffle" between different binding sites in the process of locating their optimal (preferred) sites. J Membr Biol, 1986, 90(1), 13 - 20 Mechanism of anion-cation selectivity of amphotericin B channels; Borisova MP et al.; Zero current potential and conductance of ionic channels formed by polyene antibiotic amphotericin B in a lipid bilayer were studied in various electrolyte solutions . Nonpermeant magnesium and sulphate ions were used to independently vary the concentration of monovalent anions and cations as well as to maintain the high ionic strength of the two solutions separated by the membrane . Under certain conditions the channels select very strongly for anions over cations . They are permeable to small inorganic anions . However, in the absence of these anions the channels are practically impermeable to any cation . In the presence of a permeant anion the contribution of monovalent cations to channel conductance grows with an increase in the anion concentration . The ratio of cation-to-anion permeability coefficients is independent of the membrane potential and cation concentration, but it does depend linearly on the sum of concentrations of a permeant anion in the two solutions . These results are accounted for on the assumption that a cation can enter only an anion-occupied channel to form an ionic pair at the center of the channel . The cation is also assumed to slip past the anion and then to leave the channel for the opposite solution . This model with only few parameters can quantitatively describe the concentration dependences of conductance and zero current potential under various conditions. ORL J Otorhinolaryngol Relat Spec, 1986, 48(1), 52 - 4 Deafness after treatment with ear drops containing neomycin, gramicidin and dexamethasone . A case report; Lind O et al.; We describe a patient with a polyethylene tube to the middle ear who developed severe deafness and vertigo after treatment with ear drops where neomycin B was considered to be the most likely offending agent . High concentration of this antibiotic in the ear drops and access of the solution to the round window membrane in the absence of inflammatory edema and secretion may have been significant factors contributing to this serious side effect . Less ototoxic preparations should be used in patients with perforated tympanic membranes or grommets. Biochemistry, 1985 Dec 31, 24(27), 8074 - 81 Biosynthesis of puromycin by Streptomyces alboniger: characterization of puromycin N-acetyltransferase; Vara J et al.; Puromycin N-acetyltransferase from Streptomyces alboniger inactivates puromycin by acetylating the amino position of its tyrosinyl moiety . This enzyme has been partially purified by column chromatography through DEAE-cellulose and Affigel Blue and characterized . It has an Mr of 23 000, as determined by gel filtration . In addition to puromycin, the enzyme N-acetylates O-demethylpuromycin, a toxic precursor of the antibiotic, and chryscandin, a puromycin analogue antibiotic . The Km values for puromycin and O-demethylpuromycin are 1.7 and 4.6 microM, respectively . The O-demethylpuromycin O-methyltransferase from S . alboniger, which apparently catalyzes the last step in the biosynthesis of puromycin {Rao, M . M., Rebello, P . F., & Pogell, B . M . (1969) J . Biol . Chem . 244, 112-118}, also O-methylates N-acetyl-O-demethylpuromycin . The Km values of the methylating enzyme for O-demethylpuromycin and N-acetyl-O-demethylpuromycin are 260 and 2.3 microM, respectively . These findings suggest that O-demethylpuromycin, if present in S . alboniger, would be N-acetylated and then O-methylated to be converted into N-acetylpuromycin . It might even be possible that N-acetylation of the puromycin backbone takes place at an earlier precursor. Nucleic Acids Res, 1985 Dec 20, 13(24), 8695 - 714 Investigations into the sequence-selective binding of mithramycin and related ligands to DNA; Fox KR et al.; The preferred binding sites for mithramycin on four different DNA fragments have been investigated by DNAase I footprinting . Sites containing at least two contiguous GC base pairs are protected by the antibiotic, the preferred binding site consisting of the dinucleotide step GpG (or CpC) . Related antibiotics chromomycin and olivomycin produce similar, but not identical footprinting patterns suggesting that they can recognize other sequences as well . All three antibiotics induce enhanced rates of enzyme cleavage at regions flanking some of their binding sites . These effects are generally observed in runs of A and T and are attributed to DNA structural variations induced in the vicinity of the ligand binding site . The reaction of dimethylsulphate with N7 of guanine was modified by the presence of mithramycin so that we cannot exclude the possibility that these antibiotics bind to DNA via the major groove. EMBO J, 1985 Dec 16, 4(13A), 3419 - 26 Retention of herpes simplex virus type II sequences in bglII n-transformed cells after co-transfection with a selectable marker; Saavedra C et al.; Transformation of mammalian cells by total u.v.-inactivated herpes simplex virus II (HSVII) or cloned fragments thereof (BglII n, BglII C) has been complicated both by a low efficiency of oncogenic transformation and the disappearance of viral DNA and/or viral products initially detected in the transformed cell lines . In an attempt to effect a stable integration of BglII n and to elucidate the role of HSVII in oncogenic transformation, we have co-transfected NIH 3T3 cells with pAG60, a plasmid which confers resistance to the G418 antibiotic, and plasmids containing either BglII n in its entirety (pNB2) or one of five subfragments of BglII n . Several isolated clones exhibit a transformed phenotype as expressed by rapid growth in low serum concentrations and colony formation in soft agar . We have obtained a markedly reduced frequency of biochemical transformants when co-transfecting pNB2 in comparison with the numbers obtained when cotransfecting the five subfragments . Furthermore, a greater proportion of subfragment-transfected colonies contain viral DNA, and in higher copy number, than observed in the pAG60/pNB2 clones . We have also found viral DNA to be more stably integrated in the subfragment-transfected clones than in the pNB2-transfected clones. Biochem Pharmacol, 1985 Dec 15, 34(24), 4291 - 8 Interaction of Ca2+ with cardiolipin-containing liposomes and its inhibition by adriamycin; Brenza JM et al.; The interaction of cardiolipin-containing, unilamellar liposomes with Ca2+ was assessed by flow dialysis in the presence of 2-100 microM 45Ca2+, using vesicles formed from phosphatidylcholine (PC) and from PC and cardiolipin in mole ratios from 16:1 to 1:1 . Control (PC only) vesicles bound no detectable Ca2+ . In contrast, Ca2+ binding to cardiolipin-containing vesicles was substantial and dependent on vesicle concentration . Scatchard plots for the binding were concave upward . Resolution of the data, assuming the presence of two independent classes of binding sites, indicated a high-affinity site with apparent KD = 5.57 +/- 0.48 microM (S.D.) and a second site with KD in the millimolar range . Interaction of cardiolipin-containing liposomes with Ca2+ was insensitive to monovalent cations (Na+, K+, Rb+), but was inhibited by ruthenium red much greater than La3+ greater than Mn2+ greater than Mg2+ . Progressive increases in the PC: cardiolipin ratio markedly increased the apparent KD for Ca2+ at the high-affinity site . Stoichiometry of Ca2+ binding at the site passed through a maximum at a PC: cardiolipin ratio of 4:1 . The potent antineoplastic agent adriamycin also inhibited the interaction of Ca2+ with cardiolipin-containing liposomes in a dose-dependent manner; effects were detected at 10 microM antibiotic . Unlike PC, adriamycin altered the stoichiometry of the high-affinity interaction but not the apparent KD . Adriamycin effects increased with pH in the range of the pKA of its amino group . These results suggest that inhibition by adriamycin may result from a mechanism other than simple competition for the charged head group of cardiolipin. Biochemistry, 1985 Dec 3, 24(25), 7182 - 7 L-alanosine: a noncooperative substrate for Escherichia coli aspartate transcarbamylase; Baillon J et al.; L-Alanosine, an antibiotic produced by Streptomyces alanosinicus, can be used by Escherichia coli aspartate transcarbamylase as a substrate instead of L-aspartate . The Michaelis constant of the catalytic subunit for this analogue is about 10 times higher than that for the physiological substrate, and the catalytic constant is about 30 times lower . The saturation curve of the native enzyme for L-alanosine indicates the lack of homotropic cooperative interactions between the catalytic sites for the utilization of this compound . It appears therefore that L-alanosine is unable to promote the allosteric transition . However, N-(phosphonoacetyl)-L-aspartate, a "bisubstrate analogue" of the physiological substrates, stimulates the reaction . This phenomenon is very similar to that reported by Foote and Lipscomb {Foote, J., & Lipscomb, W . N . (1981) J . Biol . Chem . 256, 11428-11433} concerning the reverse reaction using carbamylaspartate . The reaction is normally sensitive to the physiological effectors ATP and CTP . The significance of these results for the mechanism of the allosteric regulation is discussed. FEBS Lett, 1985 Dec 2, 193(2), 227 - 30 Polymyxin B inhibits phorbol 12-myristate 13-acetate, but not chemotactic factor, induced effects in rabbit neutrophils; Naccache PH et al.; The addition of the amphipathic polycationic antibiotic polymyxin B to a suspension of rabbit neutrophils results in inhibiton of the agonist (secretion of secondary granules) and antagonist (inhibition of chemotactic factor induced degranulation) properties of phorbol 12-myristate 13-acetate . On the other hand, polymyxin B does not inhibit the degranulation of the neutrophils that is induced by chemotactic factors . These results imply that the role of protein kinase C in the initiation of neutrophil functions in response to the addition of chemotactic factors is less critical than previously thought . In addition, the reversal of the inhibitory properties of phorbol esters by polymyxin B indicates that the former are mediated by the ability of the tumor promoters to activate protein kinase C . These results thus strengthen the hypothesis that protein kinase C plays important roles in the regulation (as contrasted to initiation) of neutrophil functions. Agents Actions, 1985 Dec, 17(2), 229 - 42 Metal ion-tetracycline interactions in biological fluids . Part 5 . Formation of zinc complexes with tetracycline and some of its derivatives and assessment of their biological significance; Brion M et al.; A series of studies was previously devoted to the dependence of the bioavailability of various tetracyclines on their coordination with calcium and magnesium ions . Several clinical investigations have also shown zinc to interfere with the gastrointestinal absorption of the drug in humans . On the other hand, the administration of tetracycline to rats was reported to result in the increase of the elimination rate of zinc, which could originate in zinc-tetracycline interactions in blood plasma . Formation constants for zinc complexes with tetracycline, oxytetracycline, doxycycline, minocycline, chlortetracycline and demethylchlortetracycline were thus determined at 37 degrees C in NaCl 0.15 mol . dm-3 aqueous medium . Computer simulations were then carried out to investigate the drug influence on the distribution of the low-molecular-weight fraction of zinc in human blood plasma . Zinc-tetracycline interactions in the gastrointestinal fluid were also simulated, using clinical data relative to fasting subjects as taken from the literature . No significant effect can be expected from tetracyclines on the distribution of zinc in plasma at the usual therapeutic levels . However, zinc-tetracycline interactions have been found to be determining factors for the bioavailabilities of the metal as well as of the antibiotic in the gastrointestinal fluid. Sabouraudia, 1985 Dec, 23(6), 425 - 32 Inhibition of growth and uptake of amino acids in the yeast, Candida parapsilosis, by ambruticin; Simpkin KG; The antifungal antibiotic, ambruticin, inhibits growth of Candida parapsilosis and reduces its ability to take up amino acids . Increasing growth temperature from 30 degrees C to 39 degrees C leads to a 100-fold decrease in the minimum growth inhibitory concentration . Ambruticin is 20 times more effective at pH 5 than at pH 8 and exponentially growing cultures are much less susceptible than stationary phase cells . The activity of ambruticin is also dependent on the presence of certain exogenous nutrients . When acetate or succinate (10 mM) are included in the incubation medium, ambruticin has little effect on amino acid uptake . Glucose, mannose and glycerol do not decrease the efficacy of ambruticin . Ambruticin probably inhibits growth by reducing the utilization of exogenous and intracellular carbohydrates . This leads to a fall in energy production within the cell which can be monitored as a reduction in the activity of energy-dependent transport systems. Poult Sci, 1985 Dec, 64(12), 2273 - 9 Pharmacokinetics of tetracycline in chickens after intravenous administration; Anadon A et al.; Plasma levels of tetracycline in chickens were determined after intravenous (iv) administration of a 65-mg/kg dose . The disposition kinetics of tetracycline in chickens were fitted to a two-compartment open model . Pharmacokinetic parameters were found to be: A (microgram/ml) = 2000 +/- 450, alpha (hr-1) = 4.3 +/- .5, B (microgram/ml) = 82 +/- 6, beta (hr-1) = .252 +/- .009, K12 (hr-1) = 1.515, K21 (hr-1) = .049, and K10 (hr-1) = 2.652 . Biliary excretion of tetracycline was also studied in chickens fitted with cannulae inserted into both bile ducts . The maximum values for tetracycline biliary excretion rate (407 and 606 micrograms/hr) were reached at about 1 hr after iv administration of 10- and 15-mg/kg doses . First-order rate constants for the biliary excretion, Kbi (hr-1), were .834 and .665, respectively . The cumulative biliary excretion study showed that about 7% of both administered doses was recovered from the bile within the first 6 hr . In contrast, there was a low recovery of antibiotic in the bile after oral administration of 100 and 200 mg/kg doses. J Antibiot (Tokyo), 1985 Dec, 38(12), 1691 - 8 The structure of efrotomycin; Dewey RS et al.; The antibiotic efrotomycin (I), C59H88N2O20, was isolated from cultures of Nocardia lactamdurans as an amorphous yellow powder . Mass spectral and NMR analyses show that the compound is a glycoside of the known antibiotic aurodox (II), C44H62N2O12 . Ozonolysis and hydrolysis of I produced the disaccharide V, 6-deoxy-4-O-(6-deoxy-2,4-di-O-methyl-alpha -L-mannopyranosyl)-3-O-methyl-beta-D-allopyranose . This disaccharide is attached to the 4-hydroxyl group of the hexahydropyran substructure of aurodox via a beta-linkage to C-1 of the allose. J Pediatr Surg, 1985 Dec, 20(6), 684 - 8 Extracorporeal membrane oxygenation for newborn respiratory failure; Loe WA Jr et al.; Respiratory failure is the leading cause of death in the newborn . Conventional therapy is very successful with 80% of infants weaned from ventilatory support . For neonates with severe respiratory failure, unresponsive to maximal medical therapy, extracorporeal membrane oxygenation (ECMO) offers an alternative means of management . Venoarterial bypass is achieved by cannulating the right atrium via the internal jugular vein and the aortic arch via the right common carotid artery . A 5-inch roller pump is used to circulate the blood through a 0.4 or 0.8 m2 silicone membrane lung . Management includes heparinization, intravenous alimentation, antibiotic coverage, and reduction of FiO2 and airway pressure . Thirty infants aged 12 to 186 hours were placed on ECMO . Each met strict criteria designed to predict greater than 90% mortality . Time on bypass ranged from 37 to 250 hours . Success, defined by weaning from ECMO and ventilatory support, was achieved in 23 . Twenty-one remain alive; 18 have excellent outcome with normal growth and development although follow-up is short (1 to 19 mos) . These results corroborate reports from the pioneers of the technique and further support the use of ECMO for neonates with respiratory failure unresponsive to conventional therapy. Fam Pract, 1985 Dec, 2(4), 232 - 4 Prescribing activity during a period of self-audit; Fleming DM; Prescription forms were obtained for 34 doctors who had been involved in a self-audit of psychotropic prescribing using the practice activity analysis method during the last week of February and the first of March, 1980 . The forms were provided by the UK Prescription Pricing Authority after the consent of the participating doctors had been obtained . For 11 of the recorders (group 1) prescription forms were available for February and for the remaining 23 (group 2) for March . For group 1 recorders the two control weeks in the study preceded the observation week and for group 2 recorders they followed it . The total number of prescription forms issued, the number including a psychotropic drug and the number including an antibiotic were compared in the respective observation and control weeks . In group 1 there were uniform reductions of all prescribing during the observation period as compared with the controls . The reduction was attributed to a shortfall in prescription forms identified in the last week of the month . In group 2 there were no differences . The pattern of prescribing indicated by the proportions of drugs in the various categories was consistent throughout . Thus the task of undertaking self-audit did not appear to influence the underlying activity audited. Antimicrob Agents Chemother, 1985 Dec, 28(6), 778 - 80 Decreased biliary excretion of piperacillin after percutaneous relief of extrahepatic obstructive jaundice; Blenkharn JI et al.; The biliary excretion of piperacillin has been assessed in 11 patients with obstructive jaundice due to hilar cholangiocarcinoma . After a 1-g intravenous dose administered 30 min before preliminary percutaneous transhepatic cholangiography, no drug was detected in the bile of seven patients; in four others, drug concentrations were far below the corresponding level in serum . After a period of external biliary drainage of up to 28 days, levels of antibiotic in bile after intravenous administration were only minimally increased . The results suggest that although the impairment of hepatic function may be improved by external biliary decompression when assessed by a fall in plasma bilirubin, the biliary elimination of piperacillin and related beta-lactam antibiotics may remain impaired for prolonged periods. Cancer Treat Rep, 1985 Dec, 69(12), 1387 - 89 Doxorubicin and cisplatin excretion into human milk; Egan PC et al.; Plasma and milk concentrations of doxorubicin (DOX) and cisplatin were measured after iv administration of these agents to a lactating patient with ovarian cancer . Cisplatin was undetectable in human milk . Milk concentrations of DOX often exceeded those detected in concomitant plasma samples . For DOX, the highest milk:plasma concentration ratio was 4.43:1 and was observed 24 hours after administration of the drug . The area under concentration versus time curve (AUC) for DOX was approximately the same in plasma and milk . Doxorubicinol was the major metabolite of DOX in plasma and in milk . The AUC for doxorubicinol was ten times higher in milk than in plasma . However, the total amount of anthracycline antibiotic delivered in the milk (maximum concentration of active anthracycline antibiotic: 0.24 mg/L) was negligible. Am J Obstet Gynecol, 1985 Dec 1, 153(7), 793 - 6 Delayed gentamicin elimination in patients with severe preeclampsia; McNeeley SG Jr et al.; Gentamicin is an aminoglycoside antibiotic frequently used in the treatment of mixed polymicrobial infections . Because patients with preeclampsia exhibit compromised renal function, decreased intravascular volume, and increased extravascular fluid, it was theorized gentamicin may be handled differently in normotensive versus preeclamptic patients . Eighteen patients with postpartum endometritis receiving gentamicin were divided into three treatment groups based on the presence and severity of preeclamptic symptoms . After the gentamicin steady state was achieved, serum samples were collected at 30, 150, and 450 minutes following completion of a timed 30-minute infusion . The mean half-life and gentamicin clearance in severe preeclamptic patients (3.15 hours and 91.5 ml/min) were significantly different from normotensive patients (2.38 hours and 135.9 ml/min) and mild preeclamptic patients (1.87 hours and 142 ml/min) . No significant differences in volume of distribution were seen . A high correlation between elimination rate and distribution volume was noted in normotensive patients; however, a moderate correlation was seen in patients with preeclampsia . Therefore, alterations in renal function in patients with severe preeclampsia, and not changes in volume of distribution, may be the primary cause for delayed aminoglycoside elimination. J Thorac Cardiovasc Surg, 1985 Dec, 90(6), 901 - 6 Graft detachment, a cause of incompetence in stent-mounted aortic valve allografts; Christie GW et al.; The detachment of allograft tissue from supporting stent posts has been a common mode of failure of stent-mounted aortic allografts . In an effort to reduce the localized stress loading on the tissue at the top of the stent posts, two changes were introduced to the previous fabrication protocol followed by Green Lane Hospital . Specifically, they were the use of a flexible acetyl-copolymer stent and covering of the peripheral attachment sutures with a bias strip of Dacron cloth . This study showed that these changes did not reduce the incidence of allograft failure caused by graft detachment . Unexpectedly, covering antibiotic-treated allograft tissue with a bias strip actually increased the likelihood of failure of the valve, by accelerating the biological degradation of the underlying graft aortic wall . The weakened aortic wall tissue was consequently less able to resist the high stress loadings at the top of the stent posts where detachment first occurred. Geriatrics, 1985 Dec, 40(12), 23 - 8 Managing the older bronchitis patient; Gleckman RA; In this era of cost containment, it is not appropriate to obtain a complete blood cell count, Gram's stain of sputum, sputum culture, or blood cultures for elderly outpatients with an exacerbation of chronic bronchitis . For monitoring antibiotic therapy of infectious exacerbations, clinicians rely on the patient's observations that dyspnea is less severe, and that sputum volume is reduced and appears more mucoid than purulent . These criteria may be rudimentary, but they have withstood the test of time. Clin Pharmacol Ther, 1985 Dec, 38(6), 686 - 91 Effect of aminoglycosides on the disposition of thyroid hormones and thyroglobulin; du Souich P et al.; Our study was designed to confirm the potential effects of three aminoglycosides on the disposition of thyroid hormones . Twenty-seven patients diagnosed with either cellulitis (n = 19), chronic osteitis (n = 4), or an abscess (n = 4) were selected . Thirteen patients received tobramycin, 60 to 100 mg iv q . 8 h., plus cloxacillin, 1 gm iv q . 4 h.; seven patients received netilmicin, 40 to 120 mg iv q . 8 h., plus cloxacillin, 1 gm iv q . 4 h.; and seven patients received either cloxacillin, 1.5 gm iv q . 4 h., or cefoperazone, 2 to 4 gm iv q . 12 h . for at least 7 days . Another group of six normal subjects received neomycin, 0.5 gm po q . 6 h . for 7 days . All these subjects had normal thyroid function before antibiotic dosing and none had thyroid function abnormalities . Tobramycin and cloxacillin/cefoperazone did not influence thyroid function . Netilmicin decreased the total serum concentrations of triiodothyronine (T3) from 114 +/- 9 to 75 +/- 7 ng/dl (P less than 0.01), probably because of increased clearance, as the T3 free fraction increased from 0.43% +/- 0.02% to 0.49% +/- 0.02% (P less than 0.05) . Thyroxine (T4) and reverse T3 (rT3) levels were not affected . Neomycin decreased T3 levels from 104 +/- 8 to 92 +/- 7 ng/dl (P less than 0.05) and the serum concentrations of thyroglobulin from 17.3 +/- 2.0 to 11.7 +/- 2.0 ng/ml (P less than 0.001) . Because T4 and rT3 levels did not change, our results suggest that neomycin may have directly affected the gland . We conclude that some aminoglycosides can alter the disposition of thyroid hormones. Clin Orthop, 1985 Dec, (201), 190 - 5 Closed fractures complicated by acute hematogenous osteomyelitis; Hardy AE et al.; Osteomyelitis developed at closed fracture sites in two children . The infection responded to antibiotic therapy, and the fractures healed without chronic infection developing, impairment of bone growth, or loss of function . It is rare for a closed fracture to develop acute hematogenous osteomyelitis, but the diagnosis should be considered in a child with a closed fracture in whom a fever develops or who complains of increasing pain after the fracture has been reduced and immobilized . In children, the condition has an excellent prognosis. J Gen Microbiol, 1985 Dec, 131 ( Pt 12), 3355 - 65 Investigation of the instability of plasmids directing the expression of Met-prochymosin in Escherichia coli; Caulcott CA et al.; The causes of the instability of a multicopy plasmid, pCT70, which directs the expression of calf prochymosin in Escherichia coli, were investigated . Plasmid pAT153 and its derivative, pCT54, were stable for more than 90 generations in continuous culture with glucose limitation . The multicopy plasmid pCT66, which expressed very low levels of prochymosin due to poor translational efficiency, and low copy number plasmids which efficiently expressed the prochymosin gene, were also stable . These results indicated that high level translation of the recombinant gene was the cause of the instability of pCT70 . The maximum specific growth rate of E . coli(pCT70) was reduced by 30% compared with E . coli(pCT66) . To fulfil the requirements of a production system, a dual origin plasmid with controllable copy number was developed . Both this plasmid (pMG165) and a derivative which contained the prochymosin gene (pMG168) were stable when maintained at low copy number . When the copy number of plasmid pMG168 was increased by putting replication under the control of the lambda PR promoter and the cI857 temperature sensitive repressor, expression of prochymosin was achieved . This strategy enables large-scale production of prochymosin without the need for antibiotic selection or other methods of preventing plasmid loss. Cancer Biochem Biophys, 1985 Dec, 8(2), 85 - 94 Inhibition of DNA polymerase alpha from leukemic and normal human cells by partially thiolated human deoxyribonucleic acids; Ho YK et al.; In continuing search for exploitable biochemical differences between cancer and normal cells at the level of DNA replication, leukemic and "normal" hematopoietic cells from four different, established human cell lines were grown in culture flasks, and both the DNA and the DNA polymerase alpha were isolated in each case from the harvested (5-10 g wet weight) cell pellets . The four selected cell lines included a "normal" lymphoblastoid B-cell line (RPMI-1788), a pre-B cell (NALM-6) and a T-cell (MOLT-4) acute lymphoblastic leukemias, and a promyelocytic leukemia (HL-60) . The DNA polymerase alpha enzyme of the two B-cell lines (both the leukemic and the "normal") showed the usual sensitivity toward inhibition by aphidicolin, while those from the two other leukemic cell lines were remarkably resistant to the antibiotic . Partially thiolated polycytidylic acid (MPC) strongly inhibited only the DNA polymerase alpha of the "normal" cell line, whereas the corresponding enzymes of all three leukemic cell lines were relatively insensitive to MPC . In contrast, the partially thiolated DNAs derived from the leukemic cell lines more strongly inhibited the DNA polymerase alphas of the leukemic cell lines than that of the "normal" cell line . These results indicate the existence of some structural differences between the DNA polymerase alpha enzymes (as well as between the DNAs) of human cells of different lineage and, particularly, of leukemic vs . "normal" character; such differences could be exploited in the design of selective antitemplates for chemotherapy. Semin Oncol, 1985 Dec, 12(4 Suppl 6), 65 - 70 Mitomycin-C in breast cancer; Hortobagyi GN; Mitomycin-C, an antitumor antibiotic discovered in 1958, acts as a bifunctional alkylating agent . Initial clinical trials utilized a daily schedule of administration, which led to severe and protracted myelosuppression and inadequate evaluation of the antitumor spectrum of mitomycin-C . In the early 1970s, the intermittent high-dosage schedule of administration was developed: 20 mg/m2 of mitomycin-C intravenously, every 6 to 8 weeks . An overall response rate of 35% was reported by several investigators . Subsequently, other administration schedules were attempted without improvement in therapeutic index . More recently, mitomycin-C was used in combinations with other drugs . Combinations of mitomycin-C and one of the vinca alkaloids have produced response rates of approximately 30% to 40% in patients with extensive previous treatment . In patients not previously exposed to doxorubicin, combinations of mitomycin-C and doxorubicin have offered response rates of approximately 50% . Acute toxicities of mitomycin-C are tolerable and consist of mild nausea, vomiting, and anorexia . Chronic toxicities include cumulative myelosuppression--especially thrombocytopenia--pulmonary toxicity, renal toxicity, and occasionally cardiac toxicity . Mitomycin-C is an effective antitumor agent in breast cancer and should be carefully incorporated in the therapeutic strategy of this disease. Clin Otolaryngol, 1985 Dec, 10(6), 329 - 34 Thyroglossal tract anomalies; el-Silimy OE et al.; Thyroglossal tract anomalies present most frequently before the second decade of life . Investigations should include ultrasound and thyroid isotope scan to demonstrate the presence of other functioning thyroid tissue prior to excision . Cysts demonstrating echogenic material centrally should be considered to be inflamed and surgical exploration carried out under antibiotic cover to minimize postoperative infection . Total excision of the thyroglossal tract anomaly must include the body of the hyoid bone to prevent recurrence and reduce the risk of further symptoms. Antibiot Med Biotekhnol, 1985 Dec, 30(12), 887 - 93 {Biosynthesis of lytic enzymes in a mixed culture of actinomycetes and yeasts}; Iakovleva EP et al.; It was shown that S . levoris, an organism producing levorin, formed lytic enzymes in monocultures and in mixed cultures with C . tropicalis . Stimulation of the antibiotic production in the mixed cultures depended on the activity of lysoenzymes . When their activity was lowered by addition of cobalt salts to the medium the stimulating effect on the antibiotic synthesis was not observed . In cultivation of S . levoris and C . tropicalis it is necessary to provide optimal conditions for the growth of the yeasts and synthesis of the biostimulator by them and also for the simultaneous growth of the actinomycete and production of the antibiotic and lytic enzymes by it. Laryngoscope, 1985 Dec, 95(12), 1468 - 71 Nosocomial Legionella pneumonia in a population of head and neck cancer patients; Johnson JT et al.; A prospective study of nosocomial pneumonia following major head and neck surgery was conducted when it was recognized that Legionella contaminated the hospital water supply . Legionella pneumonia had not previously been diagnosed in our hospital . Every head and neck patient with nosocomial pneumonia had specialized tests performed . During the 18-month study period, 29% of patients with nosocomial pneumonia (7 of 27) had evidence of legionellosis . The sero-group of the infecting Legionella was the same as the Legionella in the water supply . Legionella was seen exclusively in patients with clinically evident aspiration . Legionella pneumonia was not demonstrated in patients undergoing laryngectomy . We conclude that specialized testing must be employed to avoid delay in diagnosis and failure to administer specific antibiotic therapy . Legionellosis may be underdiagnosed in hospitalized patients. Hinyokika Kiyo, 1985 Dec, 31(12), 2281 - 3 {Effectiveness of tiaprofenic acid on clinical symptoms of acute simple cystitis in women}; Chiba R et al.; Acute simple cystitis is very easily cured by the proper use of an antibiotic . However, at times, such irritation symptoms in the bladder as micturition pain, pollakisuria and pyuria disappear . Consequently, medication to remove these irritation symptoms in the bladder at the earliest possible date, is required . However, there are no established standards for treatment in terms of the administration method and the administration period, etc . We gave a new non-steroid anti-inflammatory drug, tiaprofenic acid (SURGAM) to women suffering from acute simple cystitis who strongly complained of bladder irritation symptoms especially of micturition pain . The administration was carried out concurrently with an antibiotic, and its effectiveness was studied . As a result, micturition pain showed 86% improvement on the 1st day after starting administration, and it is thought that the concurrent use of this product with an antibiotic can probably remove the patients' complaints quickly and prevent the meaningless administration of antibiotics due to the persistence of symptoms and, subsequently, there is the possibility of shortening the period of administration. Jpn J Antibiot, 1985 Dec, 38(12), 3651 - 9 {Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology}; Yamamoto K et al.; Aztreonam (SQ 26,776, AZT), a new monobactam antibiotic, was fundamentally and clinically studied with the following results . Uterine and adnexal concentrations of AZT after intravenous injection of 1 g were highest 3 hours after administration in the ranges of between 18.6-23.4 micrograms/g 16.5-28.2 micrograms/g, respectively, and and rapidly decreased thereafter . Penetration of AZT into the pelvic dead space exudate was quickly recognized after intravenous injection of 1 g and its concentration 30 minutes after administration was 14.08 +/- 7.08 micrograms/ml and highest (22.35 +/- 5.85 micrograms/ml) 2 hours after administration . It gradually decreased to 8.50 +/- 2.07 micrograms/ml 6 hours after administration . Clinical effect was studied by administering 1-3 g of AZT twice a day for 3-16 days by intravenous drip infusion for 18 patients with various infections in the field of obstetrics and gynecology . Efficacy of AZT for 9 genital infection cases were excellent for 4 cases, good for 4 cases and poor for 1 case, with an overall efficacy rate of 88.9% . For 2 UTI cases, it was excellent for one case and good for the other, and for 4 pelvioperitonitis cases, excellent for 3 cases and good for 1 case . For 2 inflammation cases of the pelvic dead space, efficacy of AZT was excellent for both of them . With regard to side effect, there was only one rash case experienced . It was considered from the above results that AZT is sufficiently useful for the infections in the field of obstetrics and gynecology and also useful for various gynecologic surgery cases. Jpn J Antibiot, 1985 Dec, 38(12), 3645 - 50 {Fundamental and clinical studies of aztreonam in the field of obstetrics and gynecology}; Ushioda E et al.; Aztreonam (AZT, E-0734), a new beta-lactam antibiotic, was fundamentally and clinically studied . The following results were obtained . The serum and internal genital tissue levels for AZT after 1 g intravenous injection had been kept at more than about 20 micrograms/ml and 3.0 micrograms/g, respectively, during 1 hour . AZT was administered at 1-2 g of daily dose by intravenous injection or intravenous drip infusion to 5 patients with obstetric and gynecological infections, comprising 1 of pyometra, parametritis, Bartholin's abscess, puerperal endometritis and diffuse peritonitis . Clinical efficacy was; excellent in 1 puerperal endometritis case, good in 2 cases and poor in 2 cases . Neither side effect nor abnormal laboratory finding was observed. Jpn J Antibiot, 1985 Dec, 38(12), 3634 - 44 {Fundamental and clinical studies on aztreonam in the field of obstetrics and gynecology}; Yamamoto T et al.; Fundamental and clinical studies on aztreonam (AZT), a new synthetic monobactam antibiotic, were performed and following results were obtained . Concentration of AZT was examined in serum, internal genital tissues and retroperitoneal fluid after a single intravenous administration of 1 g dose . The venous serum level of AZT was 114.0 micrograms/ml at 10 minutes after the administration, then decreased to 7.0 micrograms/ml at 3 hours . Since concentration of AZT in examined tissues showed wide variation, it was irrelevant to calculate transfer ratio . Concentration in retroperitoneal fluid made the peak of 40.0 +/- 22.6 micrograms/ml at 1 hour after the administration, then slowly decreased to 13.4 +/- 3.2 micrograms/ml at 6 hours . Judging from above data, the transfer of AZT to retroperitoneal fluid was favorable . In clinical trial, AZT was given to 17 cases with obstetrical and gynecological infections such as endometritis, uterine adnexitis, pelvic peritonitis, parametritis and lymphocystitis . The efficacy was evaluated as excellent in 2 cases, good in 12 and poor in 3, and efficacy rate was 82.4% . No side effects were observed in any of the cases . In laboratory findings, transient elevation of liver function in 2 cases and eosinophilia in 1 case were noticed. Jpn J Antibiot, 1985 Dec, 38(12), 3609 - 18 {Fundamental and clinical studies on aztreonam in the gynecological field}; Hanada S et al.; Aztreonam (AZT), a new monocyclic beta-lactam antibiotic was studied on clinical efficacy for infectious disease in gynecological field . At about 80 minutes following intravenous injection of 1 g dose of AZT, it penetrated well into internal genital organs at therapeutic levels . Moreover it transferred very fast and enough into intrapelvic dead space exudate, and its level was kept still as high at 12 hours after administration . AZT was given to 20 women affected with gynecological infectious disease . The outcome of AZT therapy was as follows: effective in 5 out of 6 patients (83.3%) administered intravenously and in all of 14 patients (100%) received intramuscularly . Notable adverse effects or abnormal laboratory findings were not observed except 1 case of diarrhea and 2 cases of transient and slight elevation of serum CPK and transaminases . Based on these results, we may conclude that AZT is a highly effective and a very safe antibiotic for the treatment of infectious disease in gynecological field. Jpn J Antibiot, 1985 Dec, 38(12), 3606 - 8 {Tissue penetration of aztreonam in obstetrics and gynecology}; Takabayashi H et al.; The following results were obtained by measuring serum and tissue concentrations of aztreonam, a new monobactam antibiotic . Penetration into each tissue was favorable, particularly, to the portio vaginalis, but there was no conspicuous difference of the penetration among other tissues . Serum concentration tended to decrease with the lapse of time, but the concentration in each tissue did not show a specific pattern of change due to a considerable irregularity of the measured concentrations . No specific side effect was noted. Jpn J Antibiot, 1985 Dec, 38(12), 3585 - 90 {Clinical experience on aztreonam}; Seki K et al.; Aztreonam (AZT), a new monobactam antibiotic, was studied for clinical efficacy in the field of gynecologic infection . AZT was administered at a daily dose of 2 g in 2 divided doses by single shot intravenous injection . The subjects were patients with the following infections: adnexitis (6), pelvic peritonitis (5), endometritis (1) and wound abscess (1) . Good response was seen in 10 patients out of 13 . The overall efficacy rate of 76.9% was obtained . Slight increase in GOT, GPT and Al-P was seen in 1 case . It was normalized on 6th day after completion of the therapy . No notable side effects were observed. Jpn J Antibiot, 1985 Dec, 38(12), 3579 - 84 {Basic and clinical studies of aztreonam in the field of obstetrics and gynecology}; Yoshida Y et al.; Aztreonam (AZT), a new monobactam antibiotic, was basically and clinically applied to the field of obstetrics and gynecology, obtaining the following results . The pelvic dead space exudate level of AZT after 30 minutes-intravenous drip infusion of 1 g attained the peak of 22.66 micrograms/ml at 1 hour from initiation of infusion and thereafter declined gradually, contrasting the peak of 34.38 micrograms/ml of the cubital vein at 30 minutes . Total of 13 cases comprising 4 with intrauterine infection, 5 with adnexitis and 4 with pelveoperitonitis were intravenously treated with AZT at a dose of 1 g twice daily . The overall clinical results were excellent in 3 cases and good in 10 cases . No side effects were observed in any of the cases treated with AZT. Jpn J Antibiot, 1985 Dec, 38(12), 3573 - 7 {Tissue penetration and clinical experiences of aztreonam in obstetrics and gynecology}; Kohara T et al.; Tissue penetration and clinical efficacy were studied on aztreonam (SQ 26,776, AZT) in obstetrics and gynecology with the following results . Number of cases was too small to sufficiently review the penetration into each uterine tissue, the ovary and the tube after the intravenous injection of AZT 1 g . Overall clinical effect for all the 6 cases reviewed was more than "good" . Also, neither side effect nor abnormal laboratory findings were reported . From the above results, AZT was considered to be a highly useful antibiotic in obstetrics and gynecology. Jpn J Antibiot, 1985 Dec, 38(12), 3477 - 80 {Concentrations of clindamycin phosphate in lung tissues}; Ikeda T et al.; There are few reports on concentrations of antibiotics in human lung tissues . The concentrations of clindamycin (CLDM) in human lung tissues were determined in 11 patients with lung tumor who were treated with the antibiotic . In the case of 600 mg drip infusion for 1 hour, the concentrations of CLDM in lung tissues were 24 micrograms/g and 23 micrograms/g, 2 and 3 hours after the start of drip infusion, respectively . In the case of 1,200 mg drip infusion, the value reached 47 micrograms/g in 2 hours and 39 micrograms/g in 3 hours . The concentrations in lung tissues were about 4-5 times higher than in blood. J Embryol Exp Morphol, 1985 Dec, 90, 101 - 21 Membrane organization in the preimplantation mouse embryo; Pratt HP; The preimplantation mouse blastocyst consists of two differentiated tissues, the trophectoderm (a structurally and functionally polarized epithelium) and the inner cell mass . The divergence of these two cell types can be traced back to a contact dependent polarization of the surface and cytoplasm at the 8-cell stage . Membrane/cytocortical organization during this preimplantation period has been studied using freeze fracture in conjunction with the sterol-binding antibiotic filipin in an attempt to discern the molecular basis and origin of these surface asymmetries . The distribution of filipin reactivity within the different membrane domains showed that the surface polarity exhibited by trophectoderm and by blastomeres of the 8-cell stage is underlain by a heterogeneity in molecular organization of the membrane/cytocortex which may originate prior to the appearance of any overt surface polarity . The results are discussed in terms of the likely basis of this membrane/cytocortical asymmetry, its probable origins and the use of the preimplantation mouse embryo as a model system for studying the assembly of a polarized epithelium. Orthopedics, 1985 Dec, 8(12), 1492 - 4 Life-threatening clavicular osteomyelitis in two debilitated patients; Baratz M et al.; Two cases are presented of immunologically compromised patients who developed acute pyogenic clavicular osteomyelitis from direct spread of a contiguous focus . Each patient's condition declined despite antibiotic therapy drainage procedures until survival was in doubt . Both showed striking reversal of their conditions and recovery when an aggressive surgical debridement (total claviculectomy) was performed . Acute pyogenic osteomyelitis of the clavicle is uncommon and rarely reported . The special implications in our patients of this disease of the adapted therapy are discussed. Am J Infect Control, 1985 Dec, 13(6), 275 - 7 Cost-effective application of the Centers for Disease Control Guideline for Prevention of Intravascular Infections; Frawley LW; Implementation of the recommendations in the CDC Guideline for Prevention of Intravascular Infections pertaining to MDVs and 48-hour administration set changes are cost-effective . Application of antibiotic ointment to cut-down sites is also cost-effective . Although not stated in the guideline, reserving antibiotic ointment only for IV lines inserted in one site more than 3 days would appear to be cost-effective . Finally, the cost-effectiveness of using IV in-line filters cannot be determined on the basis of current existing data . More information is needed pertaining to the effect of filtration on infection rates and the cost of filtration versus the cost of a case of phlebitis. J Endocrinol, 1985 Dec, 107(3), 365 - 74 The functional significance of glycosylation of pro-opiomelanocortin in melanotrophs of the mouse pituitary gland; Jenks BG et al.; Pro-opiomelanocortin (POMC) is a glycoprotein precursor for a number of neuropeptides and peptide hormones . The functional significance of the glycosylation of POMC has never been established . Using the antibiotic tunicamycin to block glycosylation of the prohormone in the mouse pars intermedia, we have compared processing of non-glycosylated prohormone with that of glycosylated prohormone in pulse-chase experiments . The peptides produced from non-glycosylated prohormone were shown to be correct cleavage products . Therefore it was concluded that, with the possible exception of peptides from the N-terminal region of the prohormone, the carbohydrate on POMC plays no role in directing cleavage or in protecting the prohormone from random proteolysis . Tunicamycin treatment retarded N-terminal acetylation of melanotrophin but had no apparent effect on acetylation of beta-endorphin . The mouse pars intermedia synthesizes two forms of POMC which differ in their degree of glycosylation . Our results indicated that, during secretion, the melanotrophs make no distinction between peptides derived from the two prohormones. Hum Immunol, 1985 Dec, 14(4), 365 - 77 Longevity of human allospecific TLCs: mycoplasma infection as a cause of in vitro "suppression" of MLC; Rosen-Bronson S et al.; It has been suggested that allospecific T-cell clones lose specific reactivity after approximately 30 cell doublings and subsequently acquire suppressor and NK-like characteristics . We have tested this hypothesis by assaying paired functional and nonfunctional TLCs for suppressor activity in PLT and MLC cocultures . Two sets of clones were initially studied: the first pair consisted of clone S5.2B, a functional TLC, and S5.14A, a nonfunctional TLC; the second pair of clones tested was comprised of two different expansions of the same clone S5.5A (nonfunctional) and S5.5B (functional) . These experiments yielded no evidence for suppressive activity by nonfunctional clones toward functional clones, furthermore, the addition of nonfunctional clones to primary MLC assays had no effect on the level of responsiveness . Eight clones were subcloned and 89 subclones were retested for function after approximately 50 cell doublings . Generally, the subclones failed to suppress MLC proliferation . A minority of TLCs could suppress MLC responses, but this "suppression" was reversible with the addition of 2% exogenous TCGF . However, eight subclones and two parental TLC lines did suppress MLC responses in the presence or absence of TCGF, but the suppressive effects in such cocultures were reversible in the presence of tylocine, an anti-mycoplasma antibiotic . Therefore, human T-cells, cultured for extended periods, do not inexorably and universally lose specific alloreactivity and gain suppressive characteristics due to some presumed differentiative event. Drug Intell Clin Pharm, 1985 Dec, 19(12), 921 - 3 Bleomycin pneumonitis potentiated by oxygen administration; Cersosimo RJ et al.; A case of a 53-year-old man who developed acute pneumonitis after bleomycin and moderate oxygen administration is presented . The patient received bleomycin 189 U over five days for preoperative control of a squamous cell carcinoma of the right tongue and tonsil . Surgery to remove the remaining tumor was performed 19 days later . The highest intraoperative oxygen concentration was 33 percent, but 40 percent oxygen was administered for four days postoperatively . He became febrile and developed a productive cough and pulmonary infiltrates on postoperative day 4 . Despite antibiotic therapy, his pulmonary function deteriorated and 100 percent oxygen was required to maintain adequate oxygenation . He sustained a myocardial infarction on postoperative day 7 and progressively deteriorated and expired five days later . Autopsy findings were consistent with bleomycin and oxygen-induced pulmonary damage . Oxygen potentiation of bleomycin-induced pulmonary toxicity is discussed. Thorac Cardiovasc Surg, 1985 Dec, 33(6), 341 - 3 Esophago-pericardial fistula . A case report and review of the literature; Konttinen MP et al.; A case of esophago-pericardial fistula is described which was treated successfully by pericardial drainage and closure of the fistula 12 days after perforation . The condition is rare and often fatal . In 29 reported cases there were only 5 survivors . On the basis of our observation and a review of the literature it is concluded that the first step in the treatment should be pericardial drainage and antibiotic coverage, followed by elective operative closure of the fistula. Am J Med, 1985 Nov 29, 79(5B), 164 - 7 Comparative clinical evaluation of ticarcillin plus clavulanic acid versus clindamycin plus gentamicin in treatment of post-cesarean endomyometritis; Apuzzio JJ et al.; A new single-antibiotic combination of ticarcillin and clavulanic acid was compared with the standard two-drug regimen of clindamycin and gentamicin in the treatment of post-cesarean endomyometritis . The regimens were as follows: 3 g of ticarcillin plus 100 mg of clavulanic acid intravenously every four hours; or 600 mg of clindamycin intravenously every six hours plus 3 to 5 mg/kg per day of gentamicin intramuscularly . The prospective randomized schedule was calculated such that half the patients were assigned to each treatment group . The diagnosis of endomyometritis was based upon an elevated oral temperature of 100.4 degrees F or higher on any two occasions, excluding the first 24 hours after delivery, uterine tenderness, and the absence of other foci of infection . Lochial discharge was foul in most cases . Forty-seven patients were treated . Treatment was successful in all patients who received clindamycin and gentamicin; ticarcillin plus clavulanic acid failed in two of 23 (9 percent) patients . Patients in whom treatment failed did not appear to be different from those in whom treatment was successful on demographic variables or in terms of risk factors for endomyometritis . The difference between the treatment failure rates was not statistically significant . This study suggests that the single-drug combination of ticarcillin plus clavulanic acid is effective in the treatment of post-cesarean endomyometritis when compared with the standard regimen of clindamycin and gentamicin. Vet Rec, 1985 Nov 23, 117(21), 549 - 51 Influence of liver fat on experimental Escherichia coli mastitis in periparturient cows; Hill AW et al.; Eleven cows with a wide range of liver fat (5.7 to 51.4 per cent) at seven days post partum were experimentally infected in a single quarter with a capsular Escherichia coli at 10 days post partum . The results suggested that a fatty liver in itself does not influence the severity of mastitis . All animals had clinical mastitis 10 hours after infection but no animals became severely ill and no treatment was given . Four out of five animals in the group with less than 20.2 per cent liver fat had bacteria in their milk at 10 hours after infection but these bacteria were eliminated by 12 hours . The six animals in the group with more than 28.3 per cent fat in their liver retained viable bacteria in the udder for much longer; with two animals bacteria were shed and abnormal milk was secreted for up to four months despite antibiotic therapy. J Theor Biol, 1985 Nov 21, 117(2), 265 - 76 A three state model for alamethicin conductance in bilayer membranes; Bruner LJ; Alamethicin is an antibiotic which produces voltage gated channels in lipid bilayer membranes . Recently completed studies of the pressure dependence of alamethicin conductance have shown that its onset following application of a suprathreshold voltage step at a pressure of 100 MPa (1000 atm) is markedly slowed relative to that observed at ambient pressure . Furthermore, the time course of the onset of conductance becomes distinctly sigmoidal at elevated pressure, a condition which is not evident at atmospheric pressure . The decay of alamethicin conductance upon removal of suprathreshold applied voltage is also slowed by application of hydrostatic pressure, but it follows a single exponential time course at all pressures . In addition, kinetic parameters characterizing the onset and decay of conductance show distinctly different pressure dependences . These observations cannot be explained by a two state model in which alamethicin moves reversibly between nonconducting and conducting states . Therefore we re-examine critically a hypothesis made by previous workers, namely that alamethicin, in monomeric or aggregate form, moves upon application of suprathreshold voltage first from a nonconducting surface state to a nonconducting preassembly or precursor state, and then finally into a conducting state . Parameters of this three state model are related to a geometric factor which measures the degree of sigmoidal conductance response and which can be evaluated directly from experimental data . An alternative aggregation-type analysis, equivalent to that applied by Hodgkin & Huxley to the potassium conductance in squid axon, is also considered in the context of this same geometric factor . The possibility of distinguishing between these analyses on the basis of experimental data is discussed. Cutis, 1985 Nov 15, 36(5A), 15 - 20 The therapy of osteomyelitis in outpatient settings; Eron LJ; Because of rising hospital costs, the use of outpatient antibiotic therapy, both oral and parenteral, is increasing . A program for the intravenous administration of antibiotics to outpatients has been established as a freestanding outpatient clinic (Intracare) . Some diseases lend themselves to treatment in such a setting better than others . Osteomyelitis accounted for one-third of the diagnoses in the first 1,000 patients treated at Intracare . While patients are usually begun on intravenous antibiotics following initial surgical debridement in the hospital, hospitalization may be avoided entirely in some patients who undergo surgery in outpatient surgical centers and are begun on intravenous antibiotics immediately afterwards at Intracare . For outpatient use, cephalosporins are most frequently used because of their efficacy, safety, and pharmacokinetics, which allows less-frequent administration . Both cefazolin and ceftriaxone were used most frequently in the Intracare program, although the once-daily administration of ceftriaxone was considered most convenient for outpatients and allowed them to return to normal activities even while receiving antibiotic therapy. J Biol Chem, 1985 Nov 5, 260(25), 13824 - 30 The identification of N-linked oligosaccharides on the human CR2/Epstein-Barr virus receptor and their function in receptor metabolism, plasma membrane expression, and ligand binding; Weis JJ et al.; Human complement receptor type 2 (CR2) was biosynthetically labeled by pulsing SB B lymphoblastoid cells for 25 min with {35S}methionine followed by chase in the presence of excess unlabeled methionine . An Mr 134,000 polypeptide represented the major form of the receptor at the end of the pulse period, and within 1 h of chase this disappeared coincident with the appearance of the Mr 145,000 mature form of CR2 . Precursor, but not mature, CR2 was sensitive to endoglycosidase H, indicating that maturation of CR2 represented processing of N-linked high mannose oligosaccharides to the complex type . The processing of precursor CR2 was impaired by monensin . In the presence of tunicamycin an Mr 111,000 form of CR2 was synthesized by SB cells, and this did not chase into either precursor or mature CR2 . This Mr 111,000 form of CR2 did not incorporate {3H}glucosamine, indicating that it lacked both N- and O-linked oligosaccharide . The half-lives of mature CR2 and nonglycosylated CR2 pulse-labeled in the presence of tunicamycin were 13.8 and 2.8 h, respectively; the turnover rate of B1, a membrane protein normally lacking carbohydrate, was unaffected by the presence of the antibiotic . The percentage of pulse-labeled, nonglycosylated CR2 that was expressed at the cell surface after 1 h of chase in the presence of tunicamycin was 30%, identical to that of mature CR2 in cells chased in the absence of the antibiotic . However, after 6 h of chase there was no additional net accumulation of nonglycosylated CR2 at the plasma membrane, while the proportion of pulse-labeled mature CR2 at this site had risen to 81% . Therefore, N-linked oligosaccharides are essential for the stability of CR2 and have some role in its plasma membrane expression . In contrast, the observation that all three forms of CR2 bound to Sepharose C3 indicates that oligosaccharides are not necessary for the interaction between CR2 and its complement ligand. Br Med J (Clin Res Ed), 1985 Nov 2, 291(6504), 1231 - 5 Acne: double blind clinical and laboratory trial of tetracycline, oestrogen-cyproterone acetate, and combined treatment; Greenwood R et al.; Since the recent introduction of a drug regimen containing 2 mg of the antiandrogen cyproterone acetate and 50 micrograms ethinyl-oestradiol (Diane; oestrogen-cyproterone acetate) several uncontrolled reports have extolled the benefits of this drug . Double blind studies, however, are lacking . Sixty two patients with moderate or moderately severe acne were therefore included in a double blind trial of treatment for six months comparing tetracycline alone, oestrogen-cyproterone acetate alone, and a combination of these agents . Sebum excretion rates and bacterial counts were measured before, during, and after treatment, at the same time as a clinical assessment was made . At six months the acne (as assessed by overall grade) had improved by 68% in the antibiotic treated group and by 74% in the oestrogen-cyproterone treated group . The group given a combination of both agents improved by 82%, which was significantly better (p less than 0.025) than the improvement in the tetracycline treated patients . No significant difference was found between the groups given oestrogen-cyproterone alone and the combined treatment . The sebum excretion rate was suppressed by 25% in the patients in both groups receiving oestrogen-cyproterone but not in the group given antibiotics alone . Oestrogen-cyproterone acetate is as effective as antibiotics in treating acne in women, and adding antibiotics offers no advantage over using oestrogen-cyproterone on its own, although in this study the combination was more effective than tetracycline alone at six months. J Gen Microbiol, 1985 Nov, 131 ( Pt 11), 2877 - 83 The mechanism of resistance to puromycin and to the puromycin-precursor O-demethyl-puromycin in Streptomyces alboniger; Perez-Gonzalez JA et al.; Ribosomes from Streptomyces alboniger are sensitive in vitro to puromycin and, to a lesser extent, to the puromycin-precursor O-demethyl-puromycin . The puromycin-inactivating enzyme (puromycin N-acetyltransferase) from S . alboniger also N-acetylates O-demethyl-puromycin . This finding indicates that in certain antibiotic-producing organisms the antibiotic-inactivating enzymes may play a role in self-defence against toxic precursor molecules. Antimicrob Agents Chemother, 1985 Nov, 28(5), 597 - 600 Determination of ticarcillin levels in serum by high-pressure liquid chromatography; Shull VH et al.; A high-pressure liquid chromatographic method for determining the concentrations of ticarcillin in serum was developed and compared, with 93 patient sera, to a standard agar well diffusion bioassay . For analysis, serum plus temocillin, the internal standard, were extracted with chloroform-n-amyl alcohol and back extracted into phosphate buffer . A reverse-phase C18 column and an ammonium acetate-methanol mobile phase were used with detection at 242 nm . Reproducibility studies yielded coefficients of variation ranging from 2.4 to 4.7% for low, mid, and high controls . Although cefoxitin, cephalothin, and cefuroxime exhibited retention similar to that of ticarcillin, a wide range of commonly administered antibiotics and other drugs did not interfere . The high-pressure liquid chromatographic assay is an accurate, reproducible method for determining the concentration of ticarcillin in serum during multiple antibiotic therapy or when rapid results are required. Z Gastroenterol, 1985 Nov, 23(11), 597 - 602 {Conservative therapy of iatrogenic esophageal perforation}; Schulz F et al.; During 7336 diagnostic and therapeutic endoscopies of the upper gastrointestinal tract 10 perforations of the esophagus were seen (0.14%) . After diagnostic X-ray 5 patients were operated and 5 treated conservatively . The precondition for conservative treatment were immediate diagnosis and a covered perforation of the intrathoracal esophagus without communication to pleura or trachea . Treatment consisted in alimentary restriction, parenteral nutrition and high antibiotic therapy . One patient with a esophagotracheal fistula died under conservative treatment . He could not be operated because of advanced tumour disease . The others had an uncomplicated course and, after healing of the perforation, between the 5 . and 15 . day oral nutrition could be started . It is proved, that the conservative treatment of iatrogenic perforation of the esophagus is a minimal stressing and very successful therapy, if the above-mentioned conditions are followed exactly. Klin Padiatr, 1985 Nov-Dec, 197(6), 489 - 91 {Acute hematogenic osteomyelitis after impetiginized scabies}; Gaida G et al.; A 15 year old boy with scabies has been treated with local form of therapy for 3 month without effect . He was then admitted to our pediatric clinic with pyrexia and restricted movement of the right knee . The med . history, the consequent laboratory findings, positive bloodcultures, skin swabs and bone scintigraphy lead to diagnosis of acute haem . osteomyelitis . The early antibiotic therapy assured uneventful recovery. Ann R Coll Surg Engl, 1985 Nov, 67(6), 370 - 1 Complications of T-tube drainage of the common bile duct; Gillatt DA et al.; The complications associated with T-tube drainage of the common bile duct following biliary surgery were studied prospectively . A high rate of complications especially associated with T-tube removal was found . Biliary leakage and bacteraemia were the two main problems though in most cases caused minimal clinical upset . Alternatives to T-tube drainage are discussed . It is suggested that if T-tubes are to be used broad spectrum antibiotic cover should be employed at the time of removal. Diagn Microbiol Infect Dis, 1985 Nov, 3(6 Suppl), 59S - 64S Clinical impact of rapid susceptibility testing; Doern GV; The clinical impact of susceptibility testing in general, and rapid same-day susceptibility tests in particular, was assessed from two perspectives: does the performance of susceptibility testing in the laboratory influence the clinical use of antibiotics? Does laboratory susceptibility testing affect the outcome of patients with infectious diseases? The following conclusions were derived from this investigation . In vitro susceptibility testing does significantly influence antibiotic usage, but it is difficult to demonstrate a direct relationship between the results of the susceptibility tests and disease outcome . There is little objective evidence to support the contention that rapid susceptibility tests have a greater clinical impact than traditional overnight procedures . Additional studies directed at addressing this issue are clearly necessary, however; in the absence of such studies, routine performance of same-day susceptibility testing should be considered only if the cost of such testing is less than the cost of overnight procedures, or if cost is not a limiting consideration. Diagn Microbiol Infect Dis, 1985 Nov, 3(6), 515 - 9 Aspergillus osteomyelitis . Report of a case and review of the literature; Barnwell PA et al.; Aspergillus is a ubiquitous saprophytic fungus seldom pathogenic for normal hosts . Aspergillus osteomyelitis occurs infrequently and is typically limited to patients with predisposing factors, including leukocyte dysfunction, malignancy with neutropenia, steroid or antibiotic therapy, pulmonary aspergillosis, and surgical manipulation . The spine is most frequently affected, and the clinical presentation is nonspecific (50% afebrile) . Diagnosis requires demonstration of characteristic, acutely branching, broad, septate hyphae in biopsy material, and culture of Aspergillus . Therapy includes debridement of necrotic bone and loculated purulence combined with amphotericin B and possibly 5-fluorocytosine or rifampin. Am J Emerg Med, 1985 Nov, 3(6), 534 - 5 Epiglottitis: a recurrent episode in a youth; Swedo SE et al.; Epiglottitis should be suspected in the adolescent with throat pain and dysphagia out of proportion to pharyngeal inflammation . Endolateral neck radiographs or indirect laryngoscopy will confirm the diagnosis . Blood and throat or epiglottic cultures always should be obtained . Therapy consists of airway stabilization and antibiotic administration . Although epiglottitis in adolescents is often less acute and less severe than in younger children, it may be life-threatening. Arch Intern Med, 1985 Nov, 145(11), 2035 - 8 Pneumonitis complicating low-dose methotrexate therapy in rheumatoid arthritis; St Clair EW et al.; Three of 95 patients with rheumatoid arthritis who were being treated with low-dose (5 to 15 mg/wk) methotrexate sodium developed the clinical, radiographic, and pathologic features of methotrexate-associated pulmonary injury . Marked hypoxemia emphasized the severity of illness in our patients; lowest oxygen pressure values for each patient were 35 mm Hg, 42 mm Hg, and 45 mm Hg . The management of our patients with a pulmonary toxic reaction to methotrexate included discontinuing the drug treatment, antibiotic therapy until an infectious cause was excluded, and high-dose methylprednisolone . Two patients recovered and one died . Contrary to an earlier report that suggested that pneumonitis occurred only with methotrexate sodium doses exceeding 15 mg/wk, our three cases demonstrate that a severe pulmonary toxic reaction may also complicate low-dose weekly methotrexate therapy of rheumatoid arthritis. Arch Intern Med, 1985 Nov, 145(11), 1978 - 81 Cost containment of the second-generation cephalosporins by prospective monitoring at a community teaching hospital; Williams RR et al.; All patients receiving cefoxitin and cefamandole were prospectively reviewed for appropriate and inappropriate utilization . There were two eight-week survey periods . In period 1, 81 (70%) of 115 patients received cefoxitin appropriately and six (40%) of 15 patients received cefamandole appropriately . In patients receiving antibiotics inappropriately, 12 (35%) of the 34 receiving cefoxitin and eight (89%) of the nine receiving cefamandole had infections that could have been treated with less expensive, equally efficacious antibiotics . Changes in antibiotic therapy were made in 79% of patients based on our recommendations . The estimated annual cost saving for these antibiotics was $40,290 . During period 2, 73 (91%) of 80 patients were given cefoxitin appropriately and 14 (61%) of 23 patients received cefamandole appropriately . Forty-three percent of those receiving cefoxitin and 33% of those receiving cefamandole inappropriately could have been treated with a less expensive, equally efficacious antibiotic . In 88% of patients, the attending physicians followed our recommendations. Am Surg, 1985 Nov, 51(11), 627 - 9 Tenckhoff catheter placement: surgical aspects; Cronen PW et al.; A 3-year retrospective review of 110 consecutive Tenckhoff catheter placements was undertaken . Major complications were found in 3.6 per cent of cases and minor complications occurred in 30 per cent . Analysis of cases in which catheters failed revealed that obesity and prior abdominal surgery occurred in 75 per cent of these patients . Attention to these factors and the use of appropriate techniques of placement and, in special situations, the use of endoscopy and fluoroscopy have reduced the failure rate of these high-risk situations . Management of infective complications are outlined and should include continued antibiotic dialysis and catheter replacement only if persistent peritonitis or fungal peritonitis occur . With these guidelines, improved peritoneal dialysis can be undertaken with less morbidity to the patient. J Infect Dis, 1985 Nov, 152(5), 1037 - 43 Distribution and activity of amphotericin B in humans; Christiansen KJ et al.; Concentrations of amphotericin B (AmB) in tissues obtained at autopsy from eight patients were measured by high-performance liquid chromatography (HPLC) . The patients had received doses of 101-2,688 mg of antibiotic . Highest concentrations of the drug were found in the liver; in one patient the amount of AmB in the liver was 41% of the total dose . No evidence of metabolism of the drug was observed, and bioassay of ethanol extracts of tissue showed that the drug retained activity . Three of the patients had histologic evidence of aspergillar or candidal infection in tissues with concentrations of AmB ranging from 2.5 to 166 micrograms/g . With two patients, the concentrations of the drug in the tissues exceeded by greater than or equal to 10-fold the minimum inhibitory concentrations of the drug in isolates that had been obtained from the same tissues . Unknown factors present in tissues appear to limit the in vivo activity of AmB. Pediatr Pulmonol, 1985 Nov-Dec, 1(6), 328 - 32 Peripherally inserted central venous catheters for treatment of cystic fibrosis; Zanni RL et al.; Patients who have cystic fibrosis (CF) are frequently hospitalized for long-term intravenous (IV) treatment . We evaluated clinical effectiveness of the Drum-Cartridge Catheter (Abbott Laboratories) for such patients . The catheter is placed peripherally under local anesthesia via an antecubital vein into the superior vena cava or right atrium . Patients who were more than 10 years of age and who were hospitalized for IV antibiotic therapy and/or IV hyperalimentation were studied . All but 2 patients had CF . Using an aseptic technique the catheters were inserted into the basilic or cephalic vein . Chest radiographs were used to confirm the final location of the catheter . Catheters were used to administer IV antibiotics, hyperalimentation, and lipids . There were 38 catheterizations in 23 patients; several patients had repeated insertions at later admissions . The success rate of insertion was 86% with 31 of the 38 insertions initially located either in the superior vena cava or right atrium . Mean duration of catheterization was 15.4 days (range 5-49 days) . No major complications such as sepsis, catheter or clot embolism, pneumothorax, vascular perforation, or hemorrhage occurred in the patients who had DF . Complications that required displacement of catheter into the axillary vein (1 patient), and cracked catheter hub (1 patient) . This study shows that the Drum-Cartridge Catheter can be used easily for IV therapy of patients who have CF for a long duration, repeatedly, and with no major complications. J Reprod Med, 1985 Nov, 30(11), 874 - 8 Comparison of short and long courses of ampicillin for vaginal hysterectomy; Benson WL et al.; Administering perioperative antibiotic to reduce the morbidity associated with vaginal hysterectomy has become well accepted . Although both short and long courses of antibiotics are effective, the optimal length of treat