Antibiotics

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 treatment has not been well established by clinical studies . Our prospective study compared two groups of patients, one receiving a short course and the other a long course of ampicillin . Patients having vaginal hysterectomy were randomly assigned to the short or long course . Febrile morbidity, as well as serious morbidity and hospital stays, in the two groups was compared . Of 212 patients receiving the short course, 21 had febrile morbidity, while 14 of 215 patients receiving the long course had febrile morbidity . These rates were not significantly different . Furthermore, serious morbidity and length of hospital stay were not significantly different.

Ann R Coll Surg Engl, 1985 Nov, 67(6), 376 - 8
A prospective randomised controlled trial of mezlocillin versus netilmicin in biliary surgery; Gillen P et al.; A prospective randomised controlled trial of mezlocillin versus netilmicin in 133 patients undergoing biliary surgery at a district hospital is reported . Sixty-four patients received mezlocillin and 69 received netilmicin . The two groups of patients were comparable with regard to age, sex, underlying pathology and operative procedures performed . The incidence of infected bile at operation was 14.2% and both antibiotics were equally effective in reducing postoperative bacteraemia (0.75%) and wound infection (4.5%) to acceptable levels . It is concluded that netilmicin is a more cost-effective antibiotic in biliary surgery than mezlocillin.

J Antibiot (Tokyo), 1985 Nov, 38(11), 1512 - 25
Total synthesis of 3-O-demethylsporaricin A; Yasuda N et al.; The novel, semisynthetic pseudodisaccharide antibiotic, 3-O-demethylsporaricin A, was synthesized via 3-O-demethylsporaricin B obtained by glycosidation of its aminocyclitol part . The aminocyclitol part was synthesized as D,L-form from D,L-(1,2,3/4,5,6)-1,4-bis(benzyloxy-carbonylamino)-5,6-O-isopropyl idene-2,3,5,6-cyclohexanetetraol via three key steps, namely, deoxygenation, inversion of a hydroxyl group, and N-methylation . The physical and biological properties of synthetic 3-O-demethylsporaricin A and an authentic sample derived from sporaricin B were identical.

Antimicrob Agents Chemother, 1985 Nov, 28(5), 639 - 42
Randomized, prospective, and double-blind trial of new beta-lactams in the treatment of appendicitis; Lau WY et al.; A prospective, randomized, and double-blind study was conducted with 864 patients operated on for appendicitis . In early cases, including normal and acute appendicitis, one dose of antibiotic was given . The rate of postappendectomy septic complications in patients who received cefotaxime, cefoperazone, or moxalactam was very low (about 3%), and there was no statistical difference between the drugs . For late cases, including gangrenous and perforated appendicitis, the antibiotics were continued for 5 days . Moxalactam decreased significantly the septic complications in these patients when compared with the other two drugs . It is safe, free from serious toxic side effects, and more convenient and easier to administer than combination antibiotic therapy . The main disadvantage of moxalactam is its high cost, but this has to be balanced against the savings in nursing time, the cost of monitoring renal function and serum level when aminoglycosides are used, and the reduced usage and manipulation of infusion sets.

Mol Biol (Mosk), 1985 Nov-Dec, 19(6), 1603 - 9
{The role of ppGpp in the coordination of transcription of the ribosomal protein genes rplKAJL and RNA-polymerase rpoBC genes in Escherichia coli cells}; Shakulov RS et al.; Transcription of the ribosomal protein genes rplKAJL and of the RNA polymerase genes proBC in the E . coli cells depends on the level of regulatory nucleotide ppGpp . The ppGpp acts as a negative regulator of transcription of the rpoBC genes in conditions of moderate deficiency of amino acids (after the cells were shifted down from amino acid rich to minimal media) or after incomplete deacylation of tRNA exerted by addition of serine-hydroxamate, or by partial inactivation of valyl-tRNA synthetase . Rifampicin of low concentrations, which inhibit total transcription not more than to 50%, stimulates transcription of the genes rpoBC and rplKAJL . It was estimated that stimulatory effect of rifampicin results from the ability of this antibiotic to decrease synthesis of ppGpp--the negative regulator of transcription of genes rplKAJL and rpoBC.

J Antimicrob Chemother, 1985 Nov, 16(5), 637 - 42
Pharmacokinetic study of ceftazidime in bone and serum of patients undergoing hip and knee arthroplasty; Leigh DA et al.; Twenty-eight patients undergoing hip arthroplasty and 15 undergoing knee arthroplasty, received chemoprophylaxis with ceftazidime 1.0 g administered intravenously at the time of induction of anaesthesia, followed by two doses of 500 mg given intramuscularly 6 and 12 h later . The mean bone concentration in hip arthroplasty showed a general rise towards a maximum of approximately 20 mg/kg when the exposure time (interval between antibiotic injection and removal of bone sample) was 35-40 min, with values ranging from 4.4 to 21.2 mg/kg (mean 14.4 mg/kg) . The patients undergoing knee arthroplasty present a complicated pharmacokinetic problem, as the use of a tourniquet limits the exposure time . Bone concentrations of ceftazidime were highest at sampling times greater than 20 min in these patients (mean level of 15.9 mg/kg for femoral bone and 13.1 mg/kg for tibial bone).

South Med J, 1985 Nov, 78(11), 1368 - 70
Combined ketoconazole and amphotericin B treatment of acute disseminated histoplasmosis in a renal allograft recipient; Goetz MB et al.; We have reported the first case of successful treatment of disseminated histoplasmosis in a renal allograft recipient using a short course (14 days) of amphotericin B in combination with prolonged therapy (161 days) with ketoconazole . This regimen should decrease the risk of antibiotic induced nephrotoxicity, but it requires further study . Five days of treatment with ketoconazole alone was ineffective in our patient's infection . Our protocol might not be as efficacious in patients who are more profoundly immunocompromised, eg, bone marrow allograft recipients . Because relapse of histoplasmosis may occur as long as nine years after treatment, immunocompromised patients being treated with ketoconazole must have close long-term clinical follow-up.

Int J Radiat Biol Relat Stud Phys Chem Med, 1985 Nov, 48(5), 821 - 35
Sensitization of cultured Chinese hamster cells to 42 degrees C hyperthermia by pentalenolactone, an inhibitor of glycolytic ATP synthesis; Nagle WA et al.; The antibiotic pentalenolactone, a specific inhibitor of glyceraldehydephosphate dehydrogenase, was used to investigate the effect of glycolytic adenosine triphosphate (ATP) synthesis on the survival response of aerobic and hypoxic Chinese hamster cells treated with 42 degrees C hyperthermia . Data obtained with aerobic cells, incubated in balanced salt solutions supplemented with different substrates for ATP production, showed that 50 microM pentalenolactone blocked ATP synthesis via glycolysis but not by oxidative phosphorylation . The glycolytic inhibition was reversed upon transfer of the cells to antibiotic-free medium, and minimal cytotoxicity (less than 20 per cent) was observed . Hypoxic cultures were obtained by incubating dense cell suspensions (2 X 10(6)/ml) to produce metabolic oxygen depletion . Concomitant with the development of hypoxia, pentalenolactone-treated cells became ATP-depleted; cellular ATP levels were reduced by about 70-fold as compared to hypoxic cells in the antibiotic-free medium . The ATP-depleted cells were more sensitive to killing by hyperthermia . Comparison of the 42 degrees C survival curves for control and the antibiotic-treated hypoxic cells yielded a dose-modifying factor of 4 (5 per cent survival level) . The results indicate that inhibition of glycolytic ATP synthesis, for example by pentalenolactone, can selectively sensitize hypoxic cells to the lethal effects of mild hyperthermia.

Chest, 1985 Nov, 88(5), 684 - 6
Omental transposition for closure of median sternotomy following severe mediastinal and vascular infection; Seguin JR et al.; Three patients suffering from severe sternal wound infection, underlying mediastinitis, and aortic sepsis were successfully treated by radical debridement of the infected tissues and mediastinal transposition of the greater omentum . Sternomediastinal antibiotic irrigation is an accepted treatment for postoperative sternomediastinitis, but appears insufficient when infection involves underlying vascular or cardiac structures . In such circumstances, extensive sternal debridement is mandatory and healthy tissue transposition, such as omentum, is a valuable alternative.

Cancer Treat Rep, 1985 Nov, 69(11), 1315 - 6
Phase II study of aclarubicin in patients with lymphoma; Case DC Jr et al.; Aclarubicin, a new anthracycline antibiotic with less cardiotoxicity relative to doxorubicin, was utilized in 33 patients with advanced lymphoma at a dose of 100 mg/m2 iv every 3 weeks . Five patients developed partial response (2, 2, 2, 4, and 8+ months) . None of the patients who had received prior anthracycline responded to aclarubicin . The dose-limiting toxic effect was hematologic . One of ten patients having serial measurements of cardiac function had a significant reduction in left ventricular function, but cardiac symptoms did not occur.

ASDC J Dent Child, 1985 Nov-Dec, 52(6), 455 - 8
Autogenous third molar transplantation: report of case; Saravia ME et al.; This case reports the surgical autogenous transplant of a third molar into a first molar recipient site . No antibiotic therapy was prescribed . Mechanical stabilization was minimal, because most of the splinting was provided by the adjacent teeth . Twenty-one months postoperatively, the tooth exhibited normal growth and absence of morbidity . The only abnormality was a decrease in the size of the pulp chamber.

Mol Cell Biol, 1985 Nov, 5(11), 3251 - 60
Adeno-associated virus vector for high-frequency integration, expression, and rescue of genes in mammalian cells; Tratschin JD et al.; We describe the construction of an adeno-associated virus (AAV) vector in which the coding sequence of the procaryotic gene neo is expressed under the control of the major AAV promoter p40 . This AAV-neo vector allowed stable expression of neo as a dominant selective marker in mammalian cells by selection of cells which were resistant to the antibiotic geneticin (G418) . When the vector was introduced into human (293 or HeLa) cell lines by a DNA transfection procedure, stable geneticin-resistant colonies were obtained . When the vector was first packaged into AAV particles and then introduced into cells via particle infection, geneticin-resistant cells were obtained at higher frequencies than those obtained by DNA transfection . In geneticin-resistant cells the AAV-neo vector was integrated at low copy number and could be rescued by subsequent infection with wild-type AAV and the helper adenovirus or, in some cases, by infection with adenovirus alone . The rescued AAV-neo vector could then be recovered as amplified unintegrated DNA from a Hirt lysate . These results demonstrate that AAV can be used as a transducing viral vector for stable integration and expression of a foreign gene in mammalian cells . The high frequency of integration and the ability to rescue the integrated vector suggest that this vector system may be useful for selecting genes from cDNA libraries . This vector may also be useful for introduction of genes into cells which are refractory to transfection in procedures such as those involving the use of CaPO4 or DEAE-dextran.

Rontgenblatter, 1985 Nov, 38(11), 361 - 71
{Clinical picture of bacterial pneumonias and their differential diagnosis}; Wagner HH et al.; Under the influence of antibiotic therapy, bacterial pneumonias have undergone a remarkable change in the last few decades . Individual forms of pneumonia can be distinguished morphologically by their localization, the way in which they spread, their limitations, and their course . Clinically, opportunistic bacterial infections predominate . Increasingly, secondary pneumonias are observed in poststenotic areas, areas of infarction, in hypostatic areas, after aspiration, and in previously damaged lobes . Radiologic criteria for differentiating from atypical pneumonias (viruses, mycoplasmas and chlamydia) are discussed.

Thorax, 1985 Nov, 40(11), 832 - 5
Oral N-acetylcysteine and exacerbation rates in patients with chronic bronchitis and severe airways obstruction . British Thoracic Society Research Committee; Studies on the mechanism of oxidative phosphorylation: effects of specific F0 modifiers on ligand-induced conformation changes of F1; Aurovertin is a fluorescent antibiotic that binds to the catalytic beta subunits of the mitochondrial F1-ATPase and inhibits ATP synthesis and hydrolysis . ATP, ADP, and membrane energization in submitochondrial particles (SMP) alter the fluorescence of F1-bound aurovertin . These fluorescence changes are considered to be in response to the conformation changes of F1-ATPase . This paper shows that the ATP-induced fluorescence change of aurovertin bound to SMP or complex V (purified ATP synthase complex F0-F1) is inhibited when these preparations are pretreated with oligomycin or N,N'-dicyclohexylcarbodiimide (DCCD) . This inhibition is not seen with isolated F1-ATPase . These and other results have suggested that modifications of the DCCD-binding protein in the membrane sector (F0) of the ATP synthase complex are communicated to F1, thereby altering the binding characteristics of ATP to the beta subunits . By analogy, it is proposed that modifications (e.g., protonation/deprotonation) of the DCCD-binding protein effected by protonic energy alter the conformation of F1 and bring about the substrate/product binding changes that appear to be essential features of the mechanism and regulation of oxidative phosphorylation.

J Antibiot (Tokyo), 1985 Nov, 38(11), 1588 - 95
Enhancement of pyrimidine nucleoside uptake into K562 and YAC-1 cells by cadeguomycin; Wu RT et al.; Cadeguomycin markedly stimulated the uptake of thymidine, deoxycytidine and uridine into the acid-insoluble fraction of K562 human leukemic cells, but did not significantly affect adenosine incorporation . The enhancement of pyrimidine nucleoside uptake was 6 approximately 17 fold over the control . Aspartate incorporation into nucleic acid was not significantly blocked by the antibiotic, suggesting that the stimulation of pyrimidine nucleoside incorporation is not due to the inhibition of de novo pyrimidine nucleotide synthesis . Net DNA and RNA syntheses, observed by {32P}phosphate uptake, were not significantly affected by cadeguomycin . The enzymatic activity of thymidine, deoxycytidine and uridine kinases was higher in cadeguomycin-treated cells than in untreated cells, suggesting that the enhancement of pyrimidine nucleoside uptake occurs in the phosphorylation process . The stimulatory activity of cadeguomycin of thymidine uptake was reversed by guanosine and deoxyguanosine, but not by adenosine and deoxyadenosine, suggesting that intracellular metabolism and/or action of cadeguomycin is related to that of guanosine and deoxyguanosine . The stimulation of pyrimidine nucleoside incorporation by cadeguomycin was also found with YAC-1 cells, but not with the other cell lines . The enhancement effect of the antibiotic seems to be not directly related to its cytotoxicity.

Biochem Biophys Res Commun, 1985 Oct 30, 132(2), 635 - 44
Fate and biological activity of exogenous DNA sequences during serial transfections in NIH/3T3 cells; Krump-Konvalinkova V et al.; The efficiency and accuracy of serial transfections in NIH/3T3 fibroblasts were investigated with two plasmids carrying a dominant gene . One plasmid carried the activated ras oncogene of human origin inducing morphological alteration and the oncogenic phenotype of NIH/3T3 cells . The second plasmid carried the bacterial neoR gene conferring resistance to the neomycine analogue G 418 . We observed no correlation between the presence of biologically active DNAs in primary transfectants and the capacities of these DNAs to transmit the exogenous information in a second cycle of transfection . Cellular DNA of only two of 13 ras and only 1 of 3 neoR transformants could transform NIH/3T3 in a second cycle of transfections . About half of secondary transfectants, derived from those primary transfectants which did transmit the exogenous DNA, contained apparently complete exogenous sequences and transmitted it efficiently and even with the original site of integration in the host DNA in a third cycle of transfection . Exogenous DNA sequences were amplified in the majority of secondary transfectants but did not enhance biological activity in a third cycle of transfer . The exogenous DNA was found to undergo rearrangements in oncogenic transformants propagated in cell culture.

Minerva Med, 1985 Oct 27, 76(41), 1917 - 20
{Culture studies of the bile during transhepatic cholangiography}; Mannella P et al.; A bacterial examination was carried out on bile taken from 119 patients undergoing transhepatic percutaneous cholangiography (P.T.C.) due to biliary obstruction . Bacteria were found in 36.9% of cases, with greater frequency in cases of benign obstructions (69.6%) than malignant obstructions (27.2%) . The extent of obstruction was found to make no difference (stenotic or obstructive) . These results therefore confirm that a risk of infectious complications during P.T.C . exist . Susceptibility studies carried out on bile bacteria showed gentamycin to be the most effective antibiotic in the prevention and treatment of infection in these cases.

Biochemistry, 1985 Oct 22, 24(22), 6089 - 95
Cross-linking of streptomycin to the 50S subunit of Escherichia coli with phenyldiglyoxal; Melancon P et al.; {3H}Dihydrostreptomycin was covalently linked to the 50S subunit of Escherichia coli K12A19 with the bifunctional cross-linking reagent phenyldiglyoxal . The cross-linking was abolished under conditions that prevent the specific interaction of streptomycin with the ribosome . The binding primarily involved the ribosomal RNA and also a limited number of proteins, namely, L2, L6, and L17 . This suggests that the binding domain for streptomycin is close to the peptidyl transferase center, in the valley between the central protuberance and the wider lateral protuberance of the 50S subunit . This domain faces the binding domain for streptomycin which we have previously characterized on the 30S subunit {Melancon, P., Boileau, G., & Brakier-Gingras, L . (1984) Biochemistry 23, 6697-6703} . Our results indicate that the 50S subunit is involved in the binding of streptomycin to the bacterial ribosome, in addition to the 30S subunit which is generally considered as the specific target of the antibiotic . They are consistent with the occurrence of a single binding site for streptomycin on the ribosome, comprised of regions of both subunits.

Cell Immunol, 1985 Oct 15, 95(2), 276 - 87
Human natural killer cells and cytotoxic T lymphocytes require cell surface carbohydrate determinants for lytic function; Kornbluth J; Cloned and uncloned populations of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) were treated with tunicamycin, an antibiotic that inhibits N-linked glycosylation, in order to study the potential role of cell surface carbohydrate determinants in lytic function . It is shown that tunicamycin-treated NK and CTL effector cells lose killer function in a dose-dependent manner . This effect is reversible; cells washed free of tunicamycin begin to recover their killer activity within 2 to 3 days after initial treatment . Conjugate experiments indicate that killer-target cell binding is not affected by tunicamycin treatment of the NK cells . It is also shown that tunicamycin treatment of target cells does not significantly affect their ability to be lysed by NK or CTL effector cells . These studies provide evidence that carbohydrate determinants are important in the lytic mechanism of both CTL and NK cells, rather than in specific effector-target cell binding.

Biochemistry, 1985 Oct 8, 24(21), 5702 - 11
Mapping labeled sites in Escherichia coli ribosomal RNA: distribution of methyl groups and identification of a photoaffinity-labeled RNA region putatively at the peptidyltransferase center; Hall CC et al.; We have developed a method for the rapid localization of sites of ribosomal RNA labeling to limited regions (approximately 200 bases) . The method is based on the formation and polyacrylamide gel electrophoretic separation of hybrids between restriction fragments of rrnB DNA and isotopically labeled rRNA and the subsequent determination of radioactivity across the gel . Using {3H}adenine-labeled rRNA as a control sample, we optimized experimental conditions with respect to a number of variables, including rRNA:DNA stoichiometric ratio, temperature of the annealing step, and levels of nucleases . An important result is that different rRNA X DNA hybrid fragments are obtained in different yields . The method was then applied to analyses of C3H3-labeled rRNA, giving results in good accord with known and proposed sites of rRNA methylation, and of rRNA that has been photoaffinity-labeled with 5-azido-2-nitrobenzoyl-{3H}Phe-tRNAPhe, a probe directed toward the peptidyltransferase center . The latter study showed a single major site of RNA labeling, falling within bases 2445-2668 of 23S rRNA . The extent of labeling was shown to be dependent on light-induced formation of a reactive intermediate and to be decreased in the absence of poly(uridylic acid) or in the presence of puromycin . The location of this major site of labeling is consistent with recent results obtained with an analogous tRNA photoaffinity label {Barta, A., Steiner, G., Brosius, J., Noller, H . F., & Kuechler, E . (1984) Proc . Natl . Acad . Sci . U.S.A . 81, 3607-3611} and with related genetic and biochemical studies of antibiotic interaction with ribosomes suggesting that the peptidyltransferase center falls within region V (bases 2043-2625) of 23S rRNA.

Antibiot Med Biotekhnol, 1985 Oct, 30(10), 765 - 70
{Sisomycin pharmacokinetics in the perilymph and blood serum--an approach to predicting its ototoxic effect}; Firsov AA et al.; To elucidate the possibility of predicting the level of aminoglycoside antibiotic penetration into the fluids of the internal ear by the antibiotic blood levels, the pharmacokinetics of sisomicin in the perilymph and blood serum was studied on guinea pigs . The antibiotic was administered to the animals subcutaneously in doses of 50, 100 and 200 mg/kg . On the basis of the comparison of the sisomicin concentrations in the perilymph normalized against the dose it was concluded that the pharmacokinetics of sisomicin in the perilymph and blood serum of the animals was linear . Comparison of the areas under the curves of the antibiotic concentration versus time in the perilymph (AUCp) and blood serum (AUCs) showed that the tissue availability of the antibiotic in this study characterized by its penetration into the perilymph and defined by the ratio of the AUCp to AUCs amounted to 55 per cent . In a two-compartment model it was not possible to predict the antibiotic levels in the perilymph by concentrations in the blood . However, by the antibiotic blood levels it was possible to characterize in a complex the pharmacokinetic behaviour of the antibiotic in the perilymph by predicting the areas under the respective curves of the antibiotic concentration versus time . The proportional relation between the values of the AUCp and AUCs suggested that the level of the antibiotic penetration into the internal ear and consequently the intensity of the potential ototoxic effect could be more reliably predicted not by separate values of the antibiotic concentration but by the areas under curves of aminoglycoside concentrations versus time.

Antibiot Med Biotekhnol, 1985 Oct, 30(10), 760 - 5
{Effect of the combined use of rifampicin and a low-molecular immunomodulator of natural origin on the primary immune response to the antigens of a tularemia vaccinal strain}; Nikitin AV et al.; The effect of rifampicin combination with a natural low molecular immunomodulator on the primary immune response to the antigens of tularemia vaccine was studied with the methods of multifactor designing of the experiment . The dependence of the delayed hypersensitivity and antibody titer on doses of the antibiotic and immunomodulator and the time of the immunomodulator administration was manifested by the second order equation . Nomographs for precise quantitative estimation of the doses and regimens providing the maximal delayed type hypersensitivity and antibody titers were plotted.

Med Trop (Mars), 1985 Oct-Dec, 45(4), 413 - 22
{Typhoid fever in children in Tananarive (Madagascar) . Comments on 97 cases}; Charieras JL et al.; 97 cases of typhoid fever in child are reported . This disease remains frequent and even severe in tropical zone where its evolution is of endemoepidemic type . Established fever, in spite of an appropriate treatment, is one of the main features of this disease . A certain number of clinical signs call for it; although classical, some others are less significant . Complications are frequent, without any correlation between the date of hospitalizing and the beginning of the disease . They are sometimes severe but mortality rate during hospitalization is quite low . Leukoneutropenia and thrombopenia are both exceptional . Blood culture and serology are always the background of any diagnosis, the latter appearing to the authors much more valuable than the former . Sulfamethoxazole-trimethoprime is an antibiotic to be recommended in first instance . Precocity of treatment has no influence on the time of apyrexia is appearing . If hopes put on oral vaccine could be confirmed, so it might be used on a large scale for children living in endemia zones.

Ann Acad Med Singapore, 1985 Oct, 14(4), 631 - 41
Strategies for the treatment of bacterial infections in the newborn; de Louvois J et al.; Antibiotics are widely used in the treatment of premature low birth-weight babies, either as blind therapy before infection is confirmed or, more specifically against a pathogen of known antibiotic susceptibility . The requirements of an antibiotic for use in the newborn are different from those in older patients and in almost every respect there are differences in the pharmacology and pharmacokinetics of antibiotics in the very young . A wide range of bacteria are responsible for infection in the new born and the distribution of these organisms will vary not only from country to country, but also from hospital to hospital . Antibiotics in current use are less effective against bacteria infecting the newborn than they once were and the introduction of new antibiotics, notably the third generation cephalosporins, provides an opportunity to reassess current antibiotic practices . This paper outlines the general considerations for chemotherapy in small babies and attempts to identify those areas where a review of current antibiotic practice is required . It is essential that decisions regarding antibiotic policies for neonatal units should be made locally and that they reflect local experience and the range of pathogens most frequently encountered and their sensitivity patterns.

Clin Otolaryngol, 1985 Oct, 10(5), 279 - 84
Tick-borne spirochetes as a cause of facial palsy; Asbrink E et al.; Twenty consecutive patients visiting an otolaryngological department in Sweden with a facial palsy were investigated for serological signs of tick-borne spirochete infection . Four patients showed serological evidence of and had a medical history compatible with a tick-borne spirochetosis . Spinal fluid analyses were performed in 3 of these patients and showed elevated specific antispirochetal antibody titres and an increase in mononuclear cells . The importance of a correct diagnosis and of antibiotic therapy in patients with spirochete-induced facial palsy is emphasized.

J Antimicrob Chemother, 1985 Oct, 16(4), 449 - 55
The mycoplasmacidal effect of herbicolin A; Birkelund S et al.; This study was to determine if the inhibitory effect of herbicolin A to sterol-requiring members of the class Mollicutes is due to a mycoplasmastatic or a mycoplasmacidal effect . Two strains were used as test organisms, Mycoplasma capricolum (California kid) and Ureaplasma urealyticum (T-960) . Following exposure of the mycoplasmas to various inhibitory concentrations of herbicolin A for various periods of time, elimination of the antibiotic as a preliminary to demonstration of any surviving organisms was endeavoured by three different procedures: (a) serial dilution, (b) filtration through a membrane filter, and (c) separation of the organisms by centrifugation . The results of these experiments showed a mycoplasmacidal effect of herbicolin A.

J Anim Sci, 1985 Oct, 61(4), 782 - 8
The efficacy of salinomycin as a growth promotant for swine from 9 to 97 kg; Lindemann MD et al.; Six trials involving 586 pigs initially averaging 9 kg were conducted at three locations (two trials/location) to evaluate the effects of the dietary addition of 0, 27.5, 55, 82.5 and 110 ppm of a monocarboxylic polyether antibiotic, salinomycin, on feed intake, growth rate and feed efficiency of swine fed corn-soybean meal-based diets . Over the total trial (9 to 97 kg), quadratic improvements in gain (P less than .01) and feed:gain (P less than .04) occurred with increasing level of salinomycin, but feed intake was not affected (P greater than .25) . Mean improvements for all drug levels over control values for the total trial were 4.3% for daily gain (P less than .01) and 3.4% for feed:gain (P less than .01) . For the total trial, rate and efficiency of gain were optimized in pigs fed the 82.5-ppm level of salinomycin with an improvement of 5.2% in daily gain and 4.8% in feed:gain over pigs fed the control diet . The absence of any significant trial X treatment interaction suggests that the nature of the response was not dependent on differences in environment, management or other factors that existed among trial locations.

J Laryngol Otol, 1985 Oct, 99(10), 1059 - 65
Osteomyelitis in the head and neck; Balm AJ et al.; Since the advent of antibiotics osteomyelitis in the head and neck is relatively uncommon and the condition has become a sort of medical curiosity . In the last 16 years, only three cases have been seen by the second author . It is the purpose of this paper to present these cases from our experience and to show that control and cure may only be achieved by early diagnosis, appropriate antibiotic therapy and, where necessary, by radical surgery with the excision of all diseased bone and with prolonged use of antibiotics post-operatively . In cases of diagnostic difficulties the use of scintigraphy is advisable . Established osteomyelitis of the frontal bone necessitates CAT scanning of the cranium to exclude intracerebral extension.

EMBO J, 1985 Oct, 4(10), 2583 - 8
Use of gene transfer and a novel cosmid rescue strategy to isolate transforming sequences; Brady G et al.; Mouse Lewis Lung tumor DNA was ligated to a cosmid containing a geneticin (G418)/kanamycin resistance gene and transferred into NIH3T3 cells . Recipient cells were first selected for geneticin resistance and subsequently for their ability to grow as a tumour when injected into nude mice . By repeating this transfection procedure with DNA from resultant tumours, geneticin-resistant NIH3T3 cells were obtained which were tumorigenic and contained approximately 1-5 copies of the transferred cosmid . The functional oncogene was cloned by preparing cosmid libraries of third round tumour DNAs, using a cosmid which does not contain a kanamycin resistance gene . Due to the original linkage of the oncogene with the cosmid containing the kanamycin resistance gene, a series of kanamycin-resistant cosmids were isolated, five of which contained an active oncogene . Subsequent analysis showed that the oncogene present was highly related to the human N-ras gene . Using a DNA probe from the MLL N-ras gene, a non-transforming counterpart was isolated from mouse liver DNA . A comparison between the two N-ras genes showed that a mutation at the amino acid position corresponding to 61 in the human gene is responsible for transforming activity of the rescued gene.

Ann Thorac Surg, 1985 Oct, 40(4), 360 - 4
Fifteen years' experience with the aortic homograft: the conduit of choice for right ventricular outflow tract reconstruction; Kay PH et al.; Ninety-seven patients with pulmonary atresia underwent right ventricular outflow tract reconstruction using a homograft conduit . There were 46 hospital deaths (47%) . Hospital mortality was significantly related to irreversible pulmonary hypertension (p less than 0.001) and thoracotomy for ligation of bronchial collaterals (p less than 0.01) . The actuarial survival was 37 +/- 7% at 10 years . Sixteen patients undergoing recatheterization at a mean of 6 years had a mean transconduit gradient of 24 +/- 15 mm Hg . Obstructed conduits (i.e., with a gradient of greater than 50 mm Hg) were replaced in 3 patients, corresponding to 13 +/- 8% at 10 years . In each instance, the obstruction was due to neointimal hyperplasia in the Dacron tube rather than calcification of the homograft valve . The fresh, antibiotic-sterilized aortic homograft is the conduit of choice for right ventricular outflow tract reconstruction . The valve itself appears more resistant to calcification than its xenograft counterpart, and the absence of Dacron removes the problem of fibrinous peel obstructing the conduit . We now construct a tube of autologous pericardium to increase the length of the conduit and avoid complementary thoracotomy for ligation of bronchial collaterals.

Clin Orthop, 1985 Oct, (199), 280 - 3
Cefamandole levels in serum and necrotic bone; Perry H et al.; Seven patients with chronic osteomyelitis were treated by surgical debridement . Cefamandole was administered intravenously before surgery . During the debridement, cefamandole concentrations were measured in serum and necrotic bone . Although adequate levels of antibiotic were achieved in the serum, minimal or no concentration of antibiotic was found in the necrotic bone . There was only minimal penetration of cefamandole into necrotic bone.

Plast Reconstr Surg, 1985 Oct, 76(4), 630 - 2
Care of pentamadine ulcers in AIDS patients; Gottlieb JR et al.; Two cases of soft-tissue infection resulting from antibiotic therapy given AIDS patients are presented . Operative treatment resulted in a closed wound in one patient . In the other patient, who suffered from recurrent acute illnesses, nonoperative treatment resulted in slow wound contraction and epithelialization without secondary wound complications . Wound sepsis did not occur, despite the absence of normal immune function . Operation and additional hospitalization, with their attendant risks, were avoided.

Gastroenterology, 1985 Oct, 89(4), 882 - 9
Intestinal pseudoobstruction caused by diffuse lymphoid infiltration of the small intestine; McDonald GB et al.; Four young women presented with diarrhea, malabsorption, and intestinal pseudoobstruction . Intestinal biopsy specimens (both peroral and full-thickness) showed flat small intestinal mucosa, sparsity of crypts, and a widespread lymphoid infiltrate in the lamina propria, muscularis propria, and myenteric plexus . There was no neuron or nerve fiber loss or damage in the plexus; muscle cell absence in the vicinity of lymphoid cell infiltration in the muscularis propria probably accounted for the pathogenesis of pseudoobstruction . Immunochemical stains showed that the infiltrate was polyclonal, and none of the patients has developed lymphoma on clinical follow-up of 4-16 yr . Transient improvement in symptoms occurred after antibiotic therapy in 3 patients, and 1 patient had improvement after treatment with cyclophosphamide and prednisone; however, symptoms of pseudoobstruction persist in all . These cases illustrate yet another cause of intestinal pseudoobstruction which is histologically distinct from visceral myopathies and neuropathies . The pathogenesis of this illness may be related to that of diffuse immunoproliferative diseases seen in Third World countries.

Jpn J Cancer Res, 1985 Oct, 76(10), 1008 - 20
Antitumor spectrum of a new anthracycline, (2"R)-4'-O-tetrahydropyranyladriamycin, and effect on the cellular immune response in mice; Hisamatsu T et al.; (2''R)-4'-O-Tetrahydropyranyladriamycin (THP), a new anthracycline antibiotic, showed stronger inhibition of the growth of L1210, CCMT (mouse mammary adenocarcinoma) and Yoshida sarcoma in rats than did adriamycin (ADM) . The antitumor activity of THP against P388 and Meth-A (mouse fibrosarcoma) was equal or slightly superior to that of ADM . Moreover, THP was active against an ADM-resistant subline of P388 . THP at the optimal effective dose against experimental tumors had no toxic effect on the cellular immune system in normal and tumor-bearing mice.

Pharmacol Biochem Behav, 1985 Oct, 23(4), 525 - 8
Residual quantities of streptomycin sulfate in haemolymph and tissue of Heliothis virescens reared on treated diet; Sikorowski PP et al.; The study showed that streptomycin sulfate was present in both tissue and blood of insects fed with the antibiotic-treated diet . Changes from larval to pupal to adult stages were accompanied by decreases in antibiotic concentration . During transformation from pupa to adult most of the antibiotic was discarded with the meconium . Eggs from adults reared from larvae fed on the antibiotic-treated diet were free of streptomycin . The antibiotic did not adversely affect insect development.

Otolaryngol Head Neck Surg, 1985 Oct, 93(5), 663 - 5
An unusual case of laryngeal scleroma; Shum TK et al.; An unusual case of nasal and laryngeal scleroma is presented . Laryngeal scleroma should be included in the differential diagnosis of obstructing lesions of the supraglottic airway . The immunoperoxidase staining method is useful in establishing the diagnosis in cases of equivocal culture and histopathologic appearance . It can further be used as an objective test to determine the effectiveness and duration of antibiotic therapy.

Transplantation, 1985 Oct, 40(4), 347 - 53
Fungal infections in liver transplant recipients; Wajszczuk CP et al.; Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation . Twenty-six patients developed 30 episodes of significant fungal infection . Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6 . Most fungal infections occurred in the first month after transplantation . In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P less than 0.0005) . The cause of death, however, was usually multifactorial, and not solely due to the fungal infection . Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P less than 0.05) and antibiotics (P less than 0.05), longer transplant operative time (P less than 0.02), longer posttransplant operative time (P less than 0.01), duration of antibiotic use after transplant surgery (P less than 0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P less than 0.01) . Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P less than 0.05) . A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.

Aust N Z J Med, 1985 Oct, 15(5), 579 - 84
Branhamella catarrhalis, a respiratory tract pathogen; Waters MJ et al.; Branhamella catarrhalis, formerly regarded as an oropharyngeal commensal, has more recently been implicated as an opportunistic pathogen in the respiratory tract . This report describes the isolation of B . catarrhalis from two consecutive samples of empyema fluid and also from sputum in thirteen cases of lower respiratory tract disease, where the isolate was considered to be etiologically significant . The antibiotic therapy required to treat such infections is discussed.

Am J Infect Control, 1985 Oct, 13(5), 199 - 209
Infectious complications of neoplastic disease; Polsky B et al.; Progress has been made in the diagnosis and treatment of infection in patients with neoplastic disease . Among the advances is the appreciation that certain opportunistic infections occur in association with particular host immune defects and epidemiologic factors . Such immune defects are seen secondary to or as a consequence of treatment for the patient's basic disease . Improved methods such as serology, open lung biopsy, and fiberoptic bronchoscopy have allowed for earlier diagnosis and treatment of opportunistic infections . The development of empiric antibiotic regimens, particularly aminoglycosides and the antipseudomonal penicillins, have improved the outcome in the febrile neutropenic patient . The benefits of protective environments have been challenged; prophylactic antibiotics and various forms of immunotherapy are of interest but remain investigational.

Trop Doct, 1985 Oct, 15(4), 154 - 9
Management of typhoid; Cook GC; Typhoid fever is still a major problem in developing Third World countries where socioeconomic conditions and standards of hygiene are still well below standard . Prophylaxis is far from satisfactory . However, recent developments using live oral vaccines are encouraging . Specific treatment for the disease consists of chloramphenicol or co-trimoxazole; amoxycillin and ampicillin are inferior agents but are of value in several situations because their potential toxic effects are less marked . Most other agents also have drawbacks or are relatively ineffective . In the severely toxic patient, corticosteroids seem to affect prognosis favourably . Of the many other acute complications of typhoid fever, ileal perforation is the most serious; there is still controversy concerning the respective roles of conservative and surgical management, but it is clear that individual cases must be assessed on their merit . Amoxycillin, because it is very rapidly absorbed and produces very high blood concentrations, is probably the best antibiotic for the carrier state.

AJR Am J Roentgenol, 1985 Oct, 145(4), 767 - 71
Chronic osteomyelitis: monitoring by 99mTc phosphate and 67Ga citrate imaging; Alazraki N et al.; Thirteen patients with chronic osteomyelitis, treated for 6 months with rifampin, had serial 99mTc phosphate and 67Ga scans to determine their value in assessing response to treatment . In patients who responded to treatment, gallium scans were deemed more accurate than 99mTc phosphate bone scans . The gallium scans, although still abnormal at the end of 6 months of antibiotic therapy, showed an improvement trend in all the responders except one in whom fracture recurred . Worsening or lack of improvement on gallium scans predicted active bone infection in five of six "clinical-failure" patients who had documented active bone infection . 67Ga scans eventually became normal in all patients who remained asymptomatic (excluding one with recurrent fracture) . 99mTc phosphate scans became normal in only one of five clinical responders . All nonresponders had persistently abnormal scans, although after 6 months of therapy only four of seven showed worsening or no improvement on the scan . Therefore, 67Ga is preferred over 99mTc phosphate bone scans in the assessment of response to therapy in chronic bone infection . Clinical utility of the gallium scan is most significant in patients whose clinical assessment is uncertain, but routine use of this technique does not appear to be warranted . Gallium images are most valuable when obtained over a period of time, so that the trend of improvement versus nonimprovement is evident.

Am J Hosp Pharm, 1985 Oct, 42(10), 2211 - 4
Stability of clindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazolin sodium in two intravenous solutions; Bosso JA et al.; The stability and compatibility of clindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazolin sodium in two intravenous solutions were studied . Each antibiotic alone as well as each of the four two-drug combinations were examined when mixed in duplicate 100-mL glass bottles of 5% dextrose and 0.9% sodium chloride injections . Antibiotic concentration, pH, and visual appearance were recorded at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours . Antibiotic concentrations were assessed with drug-specific high-performance liquid chromatographic assays . Decreases in concentration of 10% or more from the original concentration were considered to indicate instability . All the single antibiotic solutions were stable for 48 hours . Clindamycin was stable in all combinations except with ceftizoxime in 0.9% sodium chloride injection, which measured 89.3% of its original clindamycin concentration at 48 hours . All the cephalosporins mixed with clindamycin were stable for 48 hours . Clindamycin is stable for at least 48 hours when mixed with cefoxitin sodium, cefamandole nafate, or cefazolin sodium in either 5% dextrose or 0.9% sodium chloride injections and for at least 24 hours when mixed with ceftizoxime sodium in 0.9% sodium chloride injection.

Eur J Drug Metab Pharmacokinet, 1985 Oct-Dec, 10(4), 329 - 31
Intraocular penetration of fusidic acid with topical Fucithalmic; Hansen S; Fucithalmic is a newly developed 1% microcrystalline suspension of the antistaphylococcal antibiotic fusidic acid . Penetration into the eye was investigated in twenty patients about to undergo cataract extraction . A single dose produced median antibiotic levels in the aqueous humour of 0.3 mcg/ml, maintained for at least 12 hours . Repeated doses produced significantly higher levels, median 0.8 mcg/ml, indicating some cumulative effect . The results show that fusidic acid passes the corneal aqueous barrier, and twice daily administration of Fucithalmic gives aqueous concentrations comparable with or higher than those seen after recommended systemic administration.

Am J Med, 1985 Oct, 79(4), 412 - 22
Infectious complications in heart-lung transplant recipients; Brooks RG et al.; Infectious complications were studied in 14 patients who received heart-lung transplants at Stanford University Medical Center from March 1981 to November 1983 . Twenty-nine infections occurred in 12 patients: 18 bacterial, nine viral, and two fungal . Sixteen (89 percent) of the bacterial infections occurred in the lung . Because of frequent colonization of the lower respiratory tract, the specificity of transtracheal aspiration and bronchoscopy was low . Empiric broad-spectrum antibiotic therapy was usually successful, and no patient died of bacterial infection . Cytomegalovirus infection occurred in six and herpes simplex virus infection in three patients . Two patients had invasive candidiasis at postmortem examination . This series emphasizes the importance of infection, particularly of the lung, in causing morbidity and mortality in heart-lung transplant recipients.

Hinyokika Kiyo, 1985 Oct, 31(10), 1813 - 7
{Four cases of cystitis induced by the anti-allergic drug tranilast}; Nishida T et al.; First, the cases of two patients with intractable cystitis are presented . The first case was a 72-year old man who was admitted to our clinic with bladder symptoms (pollakisuria, pain on urination, hematuria and so forth) for about one month . These symptoms were not relieved by several kinds of antibiotic therapy . For the previous three months he had been suffering from asthma bronchiale . Rizaben (tranilast) was administered for more than two months . An excretory urogram showed normal renal function, but a small bladder with trabeculation . Voiding cystourethrograms revealed bilateral VUR . Cystoscopy disclosed remarkable red areas in the bladder mucosa . A bladder biopsy was done and the pathological finding was cystitis chronica . Intravesical installation of AgNO3, steroid administration, anti-histamic and anti-allergic therapy did not resolve these symptoms . However, Chinese medicines (Choreto and Ryutanshakanto) were effective . The second case was a 39-year old woman who visited our clinic complaining of bladder symptoms with hematuria for more than two months . In the past, she had suffered from asthma bronchiale . Rizaben (tranilast) was administered for three months . On cystoscopic examination, a small amount of intravesical coagula and erythematous, edematous areas with petechiae, were observed . The intravesical installation of AgNO3, anti-histamic and antiallergic therapy and gamma-globulin were not effective, but Chinese medicine was effective . Two other cases of cystitis due to Rizaben are presented briefly . Including our cases, 24 cases of cystitis chronica or eosimophilic cystitis due to Rizaben have been reported recently.

Gen Physiol Biophys, 1985 Oct, 4(5), 493 - 500
Effect of gramicidin A and thallium ions on cation effluxes in frog sartorius muscle; Shvinka NE et al.; The effluxes of potassium, rubidium, sodium and lithium from the sartorius muscle of Rana temporaria in magnesium-Ringer solution free of sodium and potassium have been studied with the flame-emission technique . The channel-forming antibiotic gramicidin A (2.5 X X10(-7)-1 X 10(-6) mol/l) enhanced the efflux of potassium and rubidium and increased the rate constants of these effluxes . Gramicidin had small if any effect on sodium and lithium effluxes and rate constants . After 60-100 min in a gramicidin-containing medium, the potassium efflux and the corresponding rate constant reached a steady-state level . This steady-state value depended on gramicidin concentration . Effect of gramicidin on both the potassium efflux and the rate constant was partially reversible . Thallium ions (2.5 X 10(-3) and 5 X 10(-3) mol/l) in sodium- and potassium- free magnesium Ringer solution caused a large increase in effluxes of all the cations examined (K+, Rb+ and Na+) both in presence and absence of gramicidin . Possible mechanisms of gramicidin and thallium effects are discussed.

J Biol Chem, 1985 Sep 25, 260(21), 11787 - 92
Peptidase activity of macromomycin apoprotein; Zaheer A et al.; Macromomycin, an antibiotic and antitumor protein obtained from Streptomyces macromomyceticus, displayed specific aminopeptidase activity . Pure macromomycin degraded the beta-chain of insulin, a few synthetic di- and tripeptides, and a number of proteins of KB cell plasma membrane . The biological activity and the peptidase activity showed similar temperature-dependent patterns suggesting that one protein is responsible for both activities . The apoprotein contained the aminopeptidase activity while the chromophore, which displayed the antibiotic and antitumor activity, did not show any such activity.

Biochemistry, 1985 Sep 24, 24(20), 5307 - 13
3-(Bromoacetyl)chloramphenicol, an active site directed inhibitor for chloramphenicol acetyltransferase; Kleanthous C et al.; Bacterial resistance to the antibiotic chloramphenicol is normally mediated by chloramphenicol acetyltransferase (CAT), which utilizes acetyl coenzyme A as the acyl donor in the inactivation reaction . 3-(Bromoacetyl)chloramphenicol, an analogue of the acetylated product of the forward reaction catalyzed by CAT, was synthesized as a probe for accessible and reactive nucleophilic groups within the active site . Extremely potent covalent inhibition was observed . Affinity labeling was demonstrated by the protection afforded by chloramphenicol at concentrations approaching Km for the substrate . Inactivation was stoichiometric, 1 mol of the inhibitor covalently bound per mole of enzyme monomer, with complete loss of both the acetylation and hydrolytic activities associated with CAT . N3-(Carboxymethyl)histidine was identified as the only alkylated amino acid, implicating the presence of a unique tautomeric form of a reactive imidazole group at the catalytic center . The proteolytic digestion of CAT modified with 3-(bromo{14C}-acetyl)chloramphenicol yielded three labeled peptide fractions separable by reverse-phase high-pressure liquid chromatography . Each peptide fraction was sequenced by fast atom bombardment mass spectrometry; the labeled peptide in each case was found to span the highly conserved region in the primary structure of CAT, which had been tentatively assigned as the active site . The rapid, stoichiometric, and specific alkylation of His-189, taken together with the high degree of conservation of the adjacent amino acid residues, strongly suggests a central role for His-189 in the catalytic mechanism of CAT.

Med J Aust, 1985 Sep 16, 143(6), 253 - 4
Abscess of the thyroid gland presenting as a pulsatile mass; Baker SR et al.; Thyroid abscess is a rare disorder, particularly since the advent of antibiotic agents . A case of thyroid abscess, which developed without systemic disturbance, and presented as a pulsatile mass in the neck, is reported . Excision with primary closure was followed by uncomplicated recovery, and is suggested as the preferred form of management.

Hosp Pharm, 1985 Oct, 20(10), 731 - 3
Development of a pocket ruler as a guide to selected drug therapy; Wein PJ et al.; This article describes the development of a durable, plastic "pocket ruler as a guide to selected drug therapy." The "pocket guide" was developed to provide comprehensive antibiotic cost-related information about parenteral antibiotics that may aid the prescriber in drug therapy selection . Additionally, the pocket guide provides clinical information and a listing of available pharmacy services that could be useful to prescribers and other health-care professionals.

Presse Med, 1985 Sep 7, 14(29), 1551 - 6
{Alpha-chain disease}; Rambaud JC et al.; The pathological and clinical features of alpha-chain disease, its immunological diagnosis, the structural abnormalities of the abnormal immunoglobulin A compared with those of proteins of gamma and mu heavy chains diseases, the course of the disease and its present treatment, the epidemiological factors involved and their influence on pathogenesis and finally, the relationship with the "Mediterranean abdominal lymphoma" or IPSID are successively described . The stress has been placed on the latest data which refine but no not modify the first description of the disease . In the same way as studies on the synthesis and structure of proteins in heavy chain diseases will provide new data on the biosynthesis of normal immunoglobulins, so the elucidation of sequential events leading from a plasmocytic stage reversible by antibiotic therapy alone to a highly malignant immunoblastic stage should improve our knowledge of the genesis of human lymphomas.

Biochim Biophys Acta, 1985 Sep 6, 841(3), 261 - 6
Proteolytic activity of largomycin; Zaheer A et al.; Largomycin, an antibiotic and antitumor protein, purified from the culture broth of Streptomyces pluricolorescens, displayed specific proteolytic activity . Pure largomycin did not degrade a number of substrates commonly used for detection of aminopeptidase, endopeptidase and carboxypeptidase activity . Pure largomycin degraded angiotensin II, bradykinin, a few dipeptides and a number of proteins of KB cell plasma membranes . The biological activity and the proteolytic activity of largomycin showed similar temperature-dependent patterns, suggesting that one protein is responsible for both activities . The apoprotein of largomycin, which did not show antibiotic activity, contained the proteolytic activity.

Tex Heart Inst J, 1985 Sep, 12(3), 233 - 7
Successful treatment of invasive aspergillosis in a heart transplant patient; Radovancevic B et al.; Infection continues to be a major cause of mortality in cardiac transplant patients, and even though there has been significant progress in diagnosing and treating many infectious disease problems, invasive aspergillosis in the transplant patient represents a serious and usually fatal complication . Even with successful early diagnosis, the use of free amphotericin B (a polyene antibiotic) has failed to cure disseminated infection . We report the case of a 46-year-old transplant patient who failed to respond to treatment with free amphotericin B after a 7-day period of treatment for biopsy-proven pulmonary aspergillosis . However, a subsequent substitution of a liposomal form of amphotericin B was used, and the patient responded well to a total dose of 1.5 mg . After 7 months, the patient continues free of infection . This experience suggests that the introduction of liposomal amphotericin B may give new hope for treating an otherwise lethal infection.

Jpn J Antibiot, 1985 Sep, 38(9), 2638 - 46
{Therapeutic effect of dried ion exchange resin-treated human immunoglobulin (SM-4300) against severe bacterial and/or fungal infections in surgery}; Ota J et al.; A newly developed human immunoglobulin for intravenous use, SM-4300, purified by cold ethanol precipitation and ion exchange resin, has been studied in the surgery . SM-4300 has been evaluated clinically against inpatients with severe bacterial and/or fungal infections in the combined use with the antibiotics which were resistant to antibiotic therapy . Total number of 13 patients affected with various severe infections were treated with SM-4300 . Clinical effects of SM-4300 were excellent in 2 cases, good in 6, fair in 3 and poor in 2 . The efficacy rate was summarized as 61.5% . No subjective and objective clinical side effects and abnormal laboratory findings were observed . In conclusion, combination therapy with SM-4300 and antibiotics was considered to be safe and effective against severe bacterial and/or fungal infections in the surgery.

J S Afr Vet Assoc, 1985 Sep, 56(3), 139 - 42
A pulmonary giant cell carcinoma in a dog; Bastianello SS et al.; A case of a large cell anaplastic carcinoma of the giant cell type in the lungs of a 5 year-old crossbred male Labrador is discussed . The dog was weak, depressed, febrile and markedly dyspnoeic . An intermittent moist cough and auscultable crackling rales were evident . Radiographic examination was indicative of pneumonia and pulmonic neoplasia . The dog died 36 hours after admission despite antibiotic and supportive therapy . At autopsy, the neoplasm appeared as numerous firm greyish-white nodules of varying size throughout all the lung lobes whilst in the right intermediate and diaphragmatic lobes the neoplasm was completely confluent . The microscopic features included: intra-alveolar composites of cells exhibiting considerable nuclear and cytoplasmic pleomorphism; the presence of numerous giant cells scattered throughout the tumour; the occurrence of tumour emboli within both venous and lymphatic vessels; and, metastatic foci in the bronchial and mediastinal lymph nodes . These features were considered to reflect a high degree of malignancy . Comparative and aetiological aspects of bronchogenic carcinomas in man and the dog are discussed.

J Biomed Mater Res, 1985 Sep, 19(7), 751 - 6
Leaching of tobramycin from PMMA bone cement beads; von Frauhofer JA et al.; The in vitro leaching characteristics of tobramycin from acrylic resin (PMMA) bone cement beads have been determined by a radioimmune assay . Tobramycin was incorporated at two concentrations into bone cement beads fabricated from three commercial brands of acrylic resin . Antibiotic leaching followed a curvilinear relationship of the form X . Y = A . X + B . Y . All beads showed similar tobramycin leaching rates over time but the initial amount of leached material differed with the amount of tobramycin incorporated in the bead and the source of the PMMA bone cement . The data indicate that tobramycin-impregnated PMMA beads permit antibiotic leaching at a controlled rate compatible with possible clinical application.

J Pharm Sci, 1985 Sep, 74(9), 1004 - 6
Incidence of experimental fascioliasis on hepatic disposition of {3H}tetracycline and {14C}rafoxanide in rats; Galtier P et al.; {7-3H}Tetracycline and {carbonyl-14C}rafoxanide were injected intravenously into anesthetized controls and rats in which experimental fascioliasis had been induced by 20 Fasciola hepatica metacercariae . The biliary excretion (1 and 3 h, respectively) of the radioactivity consisted of approximately 4% of the administered dose . In 4-week infested rats, biliary excretion of {3H}tetracycline and hepatic levels of radioactivity were decreased, whereas bile flow did not vary and plasma clearance of the antibiotic was significantly decreased in comparison with control animals . These differences could be the result of the fascioliasis-induced decrease in the hepatic uptake of tetracycline and the limited active transport for its output into bile canaliculi . No change in {14C}rafoxanide disposition was shown in infested rats.

J Antibiot (Tokyo), 1985 Sep, 38(9), 1211 - 8
Biosynthesis of 2-deoxystreptamine; Suzukake K et al.; Extracts of Streptomyces fradiae 75-078, a producer of an antibiotic neomycin, were found to catalyze three reactions which are included in the proposed biosynthetic pathway to 2-deoxystreptamine; amination of deoxyinosose yielding deoxyinosamine, conversion of deoxyinosamine to 2-deoxystreptamine and deamination of 2-deoxystreptamine . Glutamine was effective as an amino-donor for both transamination reactions; conversions of deoxyinosose to deoxyinosamine and of aminodeoxyinosose to 2-deoxystreptamine . Conversion of deoxyinosamine to 2-deoxystreptamine, presumably including successive dehydrogenation and transamination at position 1, was stimulated by NAD+ . On DEAE-Sepharose CL-6B ion-exchange chromatography, the enzyme activity catalyzing amination of deoxyinosose and deamination of 2-deoxystreptamine was eluted as an entity (aminotransferase), while the one converting deoxyinosamine to 2-deoxystreptamine, only if the aminotransferase is supplemented, can be eluted as a separate peak (deoxyinosamine dehydrogenase) . The molecular weight of the aminotransferase was estimated to be 130,000 daltons by chromatography on Sepharose CL-6B . Enzymatic synthesis of 2-deoxystreptamine from deoxyinosose was demonstrated by the cell free extracts.

Thorax, 1985 Sep, 40(9), 671 - 6
Evaluation of jet nebulisers for use with gentamicin solution; Newman SP et al.; Recently nebulised antibiotics (gentamicin and carbenicillin) have been used successfully to treat respiratory tract infection in patients with cystic fibrosis . No information exists, however, on the choice of nebuliser or the ideal mode of operation with antibiotic solutions, which are often viscous . The aerosol output, droplet size, and nebulisation time were assessed for four common brands of jet nebuliser (Bird, DeVilbiss, Inspiron, and Upmist) used to nebulise 2 ml (80 mg) and 4 ml (160 mg) of gentamicin solution (Garamycin, Kirby-Warrick) at four compressed gas flow rates (6, 8, 10, and 12 1 . min-1) . There were considerable variations between the nebulisers, DeVilbiss and Upmist being most efficient in the release of respirable (less than 5 micron diameter) droplets . Droplet size and nebulisation time were inversely proportional to gas flow rate . Aerosol output and nebulisation time were increased by raising the volume fill from 2 to 4 ml, although nebulisation time could still be restricted to 12 minutes or less with DeVilbiss and Upmist at 12 1 . min-1 . The output of drug in droplets of below 5 micron diameter ranged from 7.2 (SE 0.4) to 71.4 (4.3) mg, according to the type of nebuliser, flow rate, and volume fill . These studies suggest that for optimal drug delivery 4 ml gentamicin solution should be nebulised either at a fixed flow rate of 10-12 1 . min-1 or with a high flow compressor . Previous unsatisfactory clinical results with antibiotic aerosols may have been due in part to incorrect choice of nebuliser or inappropriate operating conditions, or both.

Ophthalmology, 1985 Sep, 92(9), 1187 - 90
Medical management of congenital nasolacrimal duct obstruction; Nelson LR et al.; One hundred thirteen consecutive children seen with congenital nasolacrimal duct obstruction were treated with local massage and topical antibiotic ointment . The obstruction was resolved in 107 patients within eight months of initiation of this form of management . Nearly all of the children were spared a surgical procedure that probably would have been performed if early probing of the nasolacrimal system had been advocated.

J Assoc Off Anal Chem, 1985 Sep-Oct, 68(5), 990 - 9
Review of chromatographic methods for chloramphenicol residues in milk, eggs, and tissues from food-producing animals; Allen EH; Although chloramphenicol is not approved for use in food-producing animals in the United States, this broad spectrum antibiotic has been widely used to treat diseases in such animals including the lactating dairy cow . Extremely low ophthalmologic doses of chloramphenicol are known to cause aplastic anemia in humans . The residues in meat, milk, and eggs intended for human consumption cause particular public health concern because the bone marrow aplasia is not dose dependent . Furthermore, chloramphenicol, a known inhibitor of protein synthesis, also retards erythropoiesis, a condition that is dose dependent and may cause allergic hypersensitivity reactions . This paper is a review of sensitive methods that use gas, liquid, thin layer, and simple column chromatography as both determinative and cleanup steps for detecting and quantitating chloramphenicol in edible animal tissues, milk, and eggs.

Ann Thorac Surg, 1985 Sep, 40(3), 214 - 23
A survey of 77 major infectious complications of median sternotomy: a review of 7,949 consecutive operative procedures; Grossi EA et al.; Sternal wound infections developed following 77 (0.97%) of 7,949 operative procedures involving median sternotomy at New York University Medical Center from 1976 to 1984 . Risk factors associated with the development of a sternal wound infection included combined revascularization and valve replacement, early reexploration for bleeding, prolonged low cardiac output syndrome, and prolonged ventilatory support (greater than 24 hours) . Concomitant infection at other sites with the same organism as cultured from the sternum was present in 42% of the patients . Thirty-seven patients (48%) were treated with radical debridement followed by closed antibiotic irrigation . In 31 other patients (40%), the wounds were debrided and left to heal by open granulation . Both initial treatments had equally high success rates (78.4% and 74.2%, respectively) . However, the open granulation method resulted in a hospital stay that was an average of 10 days longer than the closed antibiotic irrigation method . Muscle flaps were used to expedite healing of open granulation in 9 patients . Analysis of the results of different treatment strategies revealed that if debridement was accomplished within 20 days of the initial cardiac procedure, 76% of the patients could be successfully treated with closed antibiotic irrigation . Conversely, if treatment was delayed for longer than 20 days, 81% of the patients were treated with open granulation (p less than 0.001) . Also noted was an inverse relationship between the serum blood urea nitrogen (BUN) level and the success rate of initial treatment with closed antibiotic irrigation . Patients with a serum BUN level of less than 40 mg/dl at the time of debridement had a 90% success rate as opposed to a success rate of 38% when the BUN level was 40 mg/dl or greater . The data presented suggest the following conclusions . Early diagnosis is crucial to successful treatment of sternal wound infection . When diagnosis can be established within 20 days, 80% of infections can be eradicated by the simple approach of debridement and closed antibiotic irrigation . When diagnosis is delayed, however, prompt debridement followed by muscle flaps is the procedure of choice . Open granulation alone, while successful, unnecessarily prolongs the hospital course.

Arch Dermatol, 1985 Sep, 121(9), 1195 - 6
Dermatobia hominis dermal myiasis . A furuncular lesion in a world traveler; File TM Jr et al.; A case of botfly myiasis occurred in a patient who traveled to Brazil . This infestation resembles a pyogenic furuncle, but should be a diagnostic consideration when it does not respond to antibiotic therapy in a world traveler.

Am Rev Respir Dis, 1985 Sep, 132(3), 602 - 5
Amphotericin B causes aggregation of neutrophils and enhances pulmonary leukostasis; Berliner S et al.; The influence of amphotericin B (AmB) on the aggregation of polymorphonuclear leukocytes (PMN) was examined by means of in vitro aggregometry as well as in an in vivo model of pulmonary leukostasis (PL) . The AmB caused a dose-dependent aggregation of PMN that was partially blocked by addition of serum to the drug prior to its reaction with the PMN . No aggregation of PMN was seen after the addition of nystatin, a similar polyene antibiotic . In vivo studies were conducted in rabbits, where PL was induced by an intravenous infusion of zymosan-activated plasma (ZAP) or phorbol myristate acetate (PMA), and the degree of resulting leukostasis was expressed as the number of PMN per high power field (HPF) . Animals in the control group had 6 +/- 3 PMN/HPF . This number increased to 12.4 +/- 5.6 when ZAP was infused and postmortem examination was performed 1 h later and to 17.4 +/- 4 if the examination was performed after 24 h . These numbers increased more than twice when AmB (1 mg/kg) was infused together with the ZAP . Increased PL after the infusion of ZAP and AmB was not attenuated by prior administration of methylprednisolone (30 mg/kg) to the animals . Infusions of AmB per se caused no significant PL but did cause increased pinocytosis in the pulmonary endothelium . Enhancement of PL by AmB was also examined in a model of PMA-induced PL.(ABSTRACT TRUNCATED AT 250 WORDS)

Surg Gynecol Obstet, 1985 Sep, 161(3), 261 - 5
Appendicitis in children; Gilbert SR et al.; Six hundred and fifty-one patients with appendicitis were reviewed and an over-all perforation rate of 36.5 per cent accompanied by a major complication rate of only 3.38 per cent and an over-all complication rate of 9.06 per cent was reported . This low complication rate despite a high level of perforation can be attributed to the use of antibiotic regimens effective against both aerobic and anaerobic organisms . A thorough irrigation and flushing of debris and exudate from the abdominal cavity of patients with ruptured appendicitis may improve these rates.

J Nucl Med, 1985 Sep, 26(9), 988 - 93
Effect of soft-tissue pathology on detection of pedal osteomyelitis in diabetics; Seldin DW et al.; Three-phase bone scans were performed on 30 diabetic patients suspected of having acute pedal osteomyelitis; 23 also had a pedal ulcer, seven had coexisting cellulitis, and 14 had diminished pedal pulses . Fifteen patients were receiving antibiotics at the time of the scan . A tissue diagnosis was available in 18 patients and 12 had no clinical evidence of infection on follow-up . Focal arterial hyperemia combined with focally increased activity on blood-pool and delayed (2-3 hr) scans were interpreted as acute osteomyelitis . Scans showing venous hyperemia were interpreted as soft-tissue pathology without acute osteomyelitis . Companion radiographs were reviewed independently . The sensitivity and specificity of the scans for osteomyelitis were 0.94 and 0.79, respectively, while radiographic sensitivity was 0.93 and specificity was 0.50 . The presence of soft-tissue ulcers or cellulitis, peripheral vascular disease, or recent antibiotic therapy had no significant adverse effect on the accuracy of the three-phase scan in diagnosing osteomyelitis.

Mikrobiologiia, 1985 Sep-Oct, 54(5), 719 - 23
{Biosynthetic activity of cultures of different species of the genus Actinomadura}; Toropova EG et al.; The ability to synthesize antibiotics and exoproteases was studied in 13 species belonging to the Actinomadura genus . The antibiotic and proteolytic activities were found only in A . fulvescens INA-3321 and A . citrea INA-1849 . Glycerol was shown to be the best carbon source for the growth and biosynthetic activity of A . fulvescens . A . citrea had a wider spectrum of carbon sources used for the growth and a higher proteolytic and antibiotic activity . A . citrea exerted the maximal biosynthetic activity and the best growth in a medium with starch and xylose . The effect of different nitrogen sources on the growth and biosynthetic activity of A . citrea was also studied.

Ann Otol Rhinol Laryngol Suppl, 1985 Sep-Oct, 119, 1 - 11
Endoscopic surgery for mycotic and chronic recurring sinusitis; Stammberger H; Chronic sinusitis and its complications are often caused or perpetuated by fungi . In Europe and North America Aspergillus species are the most common contaminants of the sinuses, with relatively few cases of mycoses caused by Mucor, Candida, Penicillium, Cladosporium, and Fusarium reported in the literature . Although Aspergillus and Mucor are mainly saprophytic, they may cause severe, potentially lethal complications . Consequently, therapy should include complete removal of the mycotic masses and prevention of reinfection . In nearly all cases in our experience, fungal diseases of the maxillary sinuses are secondary diseases, the pathologic conditions for which are created by chronic recurring sinusitis . Nasal endoscopy has shown that in most cases of recurring sinusitis, infection spreads from the nose into the larger sinuses, mostly from an infected anterior ethmoid . Maxillary and frontal sinuses are fully dependent on the pathophysiologic conditions in the anterior ethmoid because their ventilation and drainage pass through its complicated system of fissures and clefts into the middle nasal meatus . Endoscopic endonasal surgery of the diseased ethmoid is therefore an important element in our treatment schedule . Stenotic and/or chronically infected areas of the anterior ethmoid are identified by conventional or computed tomography . These areas then undergo endonasal operation under the guidance of rigid endoscopes . Diseased mucosa is removed, narrow or stenotic areas are widened, and the natural maxillary sinus ostium is enlarged . In many cases it is possible to remove all mycotic masses through this new window . Fenestration into the inferior nasal meatus is unnecessary with this method, and the sinus mucosa is usually left untouched . For follow-up treatment, instillations of antimycotic or antibiotic ointments are used . Even in cases of massive mucosal changes, the dependent sinuses, such as the frontal or maxillary sinuses, usually heal spontaneously after this procedure without having been treated directly . More than 140 patients with mycotic sinusitis, 48 of whom were studied and followed up for this paper, were treated by us during the last 8 years . The endoscopic surgical technique we have developed is described in detail.

J Ethnopharmacol, 1985 Sep, 14(1), 75 - 82
The medicinal and nutritional properties of Dahlia spp; Whitley GR; The common garden variety dahlia was once an important root crop and medicinal plant among the pre-Columbian Indians of central Mexico, Yucatan and Guatemala . Its roots were valued both for the nutritious inulin stored inside them and for the antibiotic compounds concentrated in the skin of the tubers . The dahlia flower was a solar symbol worn by Moctezuma and his nobles . In the modern world, dahlias cultivated as a crop might prove to be a worthy food supplement in subtropical areas.

J Foot Surg, 1985 Sep-Oct, 24(5), 335 - 8
Use of the Hickman catheter for the treatment of lower extremity infections; Williams PJ et al.; The authors discuss the use of a cuffed, Silastic catheter, which can be of great value in the reduction of morbidity when dealing with lower extremity infections . When a patient's condition demands the use of long-term antibiotic and/or aminoglyoside therapy, this indwelling central venous catheter can allow easy access to the vascular system and markedly decrease the amount of time the patient has to stay in the hospital . This form of therapy involves the patient in the treatment and displays no mortality and minimal morbidity associated with catheter placement and care.

Proc Natl Acad Sci U S A, 1985 Sep, 82(17), 6014 - 8
Changes in cell volume measured with an electrophysiologic technique; Reuss L; Epithelial cells of the gallbladder of Necturus maculosus were loaded with tetramethylammonium (Me4N+) by transient exposure of the apical (lumen-facing) surface to a solution of high Me4N+ concentration containing also the polyene antibiotic nystatin . Upon removal of nystatin, in the continued presence of Me4N+, spontaneous restoration of the native ionic permeability of the apical cell membrane was observed . At this time, external Me4N+ was removed; intracellular {Me4N+} measured with ion-sensitive microelectrodes was 2-15 mM and remained unchanged for several hours . Changes in cell volume were estimated from the changes in intracellular {Me4N+} produced by alterations in the osmolality of the mucosal bathing solution . Assuming that such changes are caused entirely by water fluxes across the apical membrane, the minimum value of its hydraulic permeability coefficient (Lp) was 1-3 X 10(-3) cm.sec-1.(osmoles/kg)-1, suggesting that an osmolality difference across the apical membrane as small as 1-3 milliosmoles/kg could explain the average rate of transepithelial water transport . These results agree with optical measurements {Persson, B . O . & Spring, K . R . (1982) J . Gen . Physiol . 79, 481-505} . The effective thickness of the apical unstirred layer was estimated from the time courses of both the apical membrane voltage and the response of an extracellular K+-sensitive microelectrode to an increase in {K+} in the mucosal bath . Since changes in concentration of the osmotically active solute at the membrane surface were thus shown to be significantly delayed by diffusion, the Lp value, calculated assuming a step-change in osmolality, is an underestimate.

Circulation, 1985 Sep, 72(3 Pt 2), II77 - 83
Long-term follow-up of patients with synthetic right heart conduits; Jonas RA et al.; Between 1971 and 1983, 201 patients received synthetic right heart conduits, predominantly porcine-valved Dacron conduits, at The Children's Hospital, Boston . There were 45 hospital deaths (22%) . Follow-up has been achieved in 148 of 156 survivors (95%) . Thirty-four conduits have been replaced, all because of conduit obstruction . The actuarial freedom from conduit replacement was 81% at 5 years, 61% at 7 years, and 0% at 10 years for valved conduits . There was no significant difference to 5 years in reoperation rate between patients with Carpentier-Edwards and those with Hancock conduits . Patients older than 18 years at the time of conduit insertion were 92% free of conduit replacement at 5 years . Those with nonvalved conduits were 100% reoperation free at 4 years . The actuarial survival of patients with valved conduits was 91% at 5 years and 83% at 10 years . The poor performance of porcine-valved tightly woven Dacron conduits warrants a change to use of an alternative conduit, particularly in smaller children . Possible alternatives include antibiotic-sterilized homografts and valved or nonvalved high-porosity knitted Dacron conduits appropriately pretreated with collagen impregnation or fibrin glue.

Mol Cell Biol, 1985 Sep, 5(9), 2325 - 31
Suppression of the hypomethylated Moloney leukemia virus genome in undifferentiated teratocarcinoma cells and inefficiency of transformation by a bacterial gene under control of the long terminal repeat; Niwa O; The Moloney leukemia virus (M-MuLV) genome was introduced into undifferentiated teratocarcinoma cells by transfection of a plasmid with the virus genome linked to pSV2neo, which carries a bacterial drug resistance gene, neo, or by cotransfection with pSV2neo . In the resulting cells, the M-MuLV genome remained hypomethylated, but its expression was suppressed in cells in an undifferentiated state . The pattern of DNA methylation of the viral genome remained unchanged when the cells were induced to differentiate into epithelial tissues . However, spontaneous M-MuLV expression was detected with differentiation of the cells . To determine to what extent the viral long terminal repeat (LTR) was responsible for this suppression in undifferentiated cells, I constructed plasmids in which neo was placed under the control of the promoter sequence of the dihydrofolate reductase gene or the M-MuLV LTR, and compared the biological activities of the plasmids in Ltk- cells and in undifferentiated teratocarcinoma cells . In Ltk- cells, these plasmids were highly efficient in making the cells resistant to selection by G418 . However, in undifferentiated teratocarcinoma cells, the M-MuLV LTR promoted neo gene expression at only 10% of the expected efficiency, as compared with the expression of the neo gene under the control of the simian virus to or dihydrofolate reductase promoter . Thus, the mechanisms of gene regulation are not the same in undifferentiated and differentiated teratocarcinoma cells.

Trop Med Parasitol, 1985 Sep, 36(3), 135 - 9
Cytofluorometry as a method for the differentiation of trypanosomes; Muhlpfordt H et al.; The DNA binding guanine specific antibiotic, chromomycin A3, has been evaluated for fluorescence intensity measurements of T . cruzi, T . brucei brucei and T . musculi . Optimal fixation and staining conditions have been determined . The fluorometry was performed with a microscope photometer equipped with electronic systems for short time excitation of 7 milliseconds and operation control . The trypomastigote bloodstream forms of these species have a different chromomycin specific DNA content . The total DNA content of T . cruzi was 2.1-fold higher than for T.b . brucei and 2.3-fold higher than for T . musculi . The nuclear DNA content also was higher in T . cruzi . The nuclear DNA values were recorded to be 1.6-fold greater than in T.b . brucei and 2.0-fold greater than in T . musculi . The amount of the kinetoplast DNA of T . cruzi was shown to be 3.2-fold higher than in T . musculi and 11.7-fold higher than in T.b . brucei . The higher total DNA of T.b . brucei in relation to T . musculi was based on the nuclear values because the content of the kinetoplast DNA of T.b . brucei was 3.7-fold smaller than of T . musculi . The kDNA comprised 25% in T . cruzi, 18% in T . musculi and only 4% in T.b . brucei of the total amount of the chromomycin specific DNA . The chromomycin fluorescence intensities of the DNA of trypanosomes were subjected to a statistical model of discriminant analysis . It was possible to get perfect separation of the three trypanosome species . The hit rate was 100%.

J Gen Microbiol, 1985 Sep, 131 ( Pt 9), 2431 - 41
Genetic and biochemical characterization of the red gene cluster of Streptomyces coelicolor A3(2); Feitelson JS et al.; Production of the red antibiotic, undecylprodigiosin, by Streptomyces coelicolor A3(2) was studied by DNA cloning and biochemical analysis . Over 21 kb of genomic DNA were cloned, in several segments, into plasmid vectors . The cloned DNA 'complemented' several specific mutations in the red gene cluster . Four red genes (redA, B, E, and F) were mapped to different regions within the cloned DNA . Screening with redE probes for DNA homologies among various streptomycetes revealed hybridizing DNA in three strains, one of them not known to synthesize prodigiosin pigments . Biochemical studies using protoplasted cells revised our interpretation of the nature of redE and redF mutations . Two forms of undecylnorprodigiosin: S-adenosylmethionine O-methyltransferase activity on gel filtration columns were detected: a very high molecular mass peak (greater than 5 MDal) and a 49 kDal) and a 49 kDal peak . Analyses of extracts from red mutants suggested that these two forms are related, and that at least the redE and redF gene products are necessary for O-methyltransferase activity in vivo . Lack of activity of the redE gene in a heterologous host, S . glaucescens, is consistent with the necessity for a biosynthetic complex involving several red gene products for efficient expression . Experiments in liquid antibiotic production medium indicated that prodigiosin compounds in S . coelicolor are examples of 'secondary metabolites' whose synthesis lags behind that of cell mass . The peak of specific activity of O-methyltransferase coincided with the 'late exponential' phase of growth . Thus, understanding the genetic regulation of undecylprodigiosin biosynthesis in S . coelicolor may be relevant to other antibiotic production pathways, and perhaps to 'secondary' metabolism in general.

Antibiot Med Biotekhnol, 1985 Sep, 30(9), 657 - 62
{Inhibitor of aminoglycoside phosphotransferases from Micromonospora sp.--a producer of sisomicin}; Griaznova NS et al.; A substance inhibiting the activity of aminoglycoside-3-'-phosphotransferases of both the actinomycetous and the bacterial origin was detected in the filtrates of the culture fluid and mycelium of Micromonospora sp . producing sisomicin . The activity of the substance against the aminoglycoside inactivating enzymes of different types was studied . It was shown that the quantity of the inhibitor in the culture fluid of Micromonospora sp . correlated with intensity of sisomocin production . Under conditions not providing production of the antibiotic the inhibitory activity was lacking . The inhibitor was purified by ion exchange chromatography on Amberlite CG-50 and KM-cellulose (NH+4 form), gel filtration through Sefadex G-50 and preparative paper chromatography . Stability of the inhibitor at different pH values and different temperatures, its sensitivity to certain enzymes and behaviour in high voltage electrophoresis were studied . The results of ultrafiltration showed that the molecular weight of the inhibitor was relatively low: less than 1000 D.

Gen Comp Endocrinol, 1985 Sep, 59(3), 449 - 52
The effects of cortisol and actinomycin D injections on chloride cells and branchial Na+ -K+ -ATPase in rainbow trout (Salmo gairdneri); Eib DW et al.; Injections of cortisol, actinomycin D, or combined administration of the hormone and the antibiotic did not effect rainbow trout (Salmo gairdneri) branchial Na+ -K+ -ATPase activity . Numbers of chloride cells also did not change following cortisol and actinomycin D treatment . These results are discussed in light of a similar report concerning Atlantic salmon (Salmo salar).

J Bacteriol, 1985 Sep, 163(3), 1016 - 20
Plasmid genes required for microcin B17 production; San Millan JL et al.; The production of the antibiotic substance microcin B17 (Mcc) is determined by a 3.5-kilobase DNA fragment from plasmid pMccB17 . Several Mcc- mutations on plasmid pMccB17 were obtained by both transposon insertion and nitrosoguanidine mutagenesis . Plasmids carrying these mutations were tested for their ability to complement Mcc- insertion or deletion mutations on pMM102 (pMM102 is a pBR322 derivative carrying the region encoding microcin B17) . Results from these experiments indicate that at least four plasmid genes are required for microcin production.

Cancer Res, 1985 Sep, 45(9), 4224 - 8
Effect of poly(adenosine diphosphate-ribose) polymerase inhibitors on neocarzinostatin-induced G2 delay in HeLa-S3 cells; Iseki S et al.; The antitumor antibiotic neocarzinostatin (NCS), which produces single-strand breaks in mammalian cell DNA in vivo, stimulated the activity of chromatin bound enzyme, poly(ADP-ribose) polymerase in HeLa-S3 cells . Because of the possible causal relationship between the poly ADP-ribosylation of chromatin protein and NCS-induced temporary G2 arrest in the cell cycle, several classes of inhibitors of poly(ADP-ribose) polymerase were examined to evaluate the effect on NCS-induced polymerase activity as well as on progression in the cell cycle of synchronized HeLa cells which had been treated with NCS in G2 . Compared at the same concentration of 2 mM, the polymerase-inhibiting activity was larger in the order of thymidine, 3-aminobenzamide, nicotinamide, theophylline, and caffeine . Among these agents, caffeine, theophylline, and thymidine caused a reduction in the G2 delay in this order by stimulating the cells to undergo mitosis after NCS treatment . However, 3-aminobenzamide and nicotinamide were poor reducers, if any, of NCS-induced G2 delay . These results suggest that there is not a direct involvement of poly ADP-ribosylation of chromatin protein in the mechanism of NCS-induced G2 delay . The effect of caffeine on G2 delay will probably be independent of its activity as a poly(ADP-ribose) polymerase inhibitor.

Proc Soc Exp Biol Med, 1985 Sep, 179(4), 529 - 38
Biological activity of phenolic compounds . Hepatic cytochrome P-450, cytochrome b5, and NADPH cytochrome c reductase in chicks and rats fed phenolic monomers, polymers, and glycosides; Klasing SA et al.; Eight experiments were conducted to determine effects of a phenolic polymer (Kraft wood lignin, Indulin), phenolic glycosides (cane molasses and wood molasses), and phenolic monomers (vanillin, vanillic acid, ferulic acid, and p-coumaric acid) on liver cytochromes P-450, cytochrome b5, and NADPH cytochrome c reductase in chicks and rats . Chicks fed 6.0% lignin had a higher (P less than 0.01) cytochromes P-450 content than did chicks fed 0% fiber, 6.0% wood cellulose (Solka Floc), or 6.0% arenaceous flour . NADPH cytochrome c reductase activity was not affected by treatment . Chicks fed 12.0% wood molasses had a higher (P less than 0.06) cytochromes P-450 level than did chicks fed 0% fiber or 6.0% wood molasses . Cane molasses incorporated at both 6.0 and 12.0% of the diet induced (P less than 0.05) cytochromes P-450 content over those of control-fed birds . Chicks fed 6.0% lignin, with or without antibiotic (bacitracin:neomycin sulfate, 2:1), had a higher (P less than 0.01) cytochromes P-450 level than did chicks fed control diets, with or without antibiotic . Additionally, chicks fed 6.0% lignin had lower (P less than 0.01) intestinal diaminopimelic acid (DAP) levels than did chicks fed 0% fiber . Rats fed 0% fiber, 6.0% wood cellulose, 6.0% arenaceous flour, or 6.0% lignin exhibited no difference in cytochrome level or activity among treatments . Chicks fed 0.5% vanillin, 0.5% vanillic acid, 0.5% ferulic acid, or 0.5% p-coumaric acid had comparable cytochromes level and activity compared with chicks fed no phenolics . Chicks fed 0.5% p-coumaric acid had lower (P less than 0.05) rates of gain than did chicks fed control or other phenolic-containing diets . Rats fed these phenolics had similar cytochromes P-450 content among treatments.

Andrologia, 1985 Sep-Oct, 17(5), 513 - 6
{Congenital fistula of the raphe penis}; Ulrich R et al.; One case of a congenital fistula of the raphe penis with gonorrhoea is reported . In this case spectinomycin seemed to fail in therapy, because pus was still remaining in the fistula, but not in the urethra . As the antibiotic resistogram did not prove our assumption, we tried the double dose and succeeded in killing the bacteria.

Acta Virol, 1985 Sep, 29(5), 432 - 48
Rickettsiae as organisms; Ormsbee RA; Although most pathogenic rickettsiae are obligate intracellular parasites, it is clear that they are bacteria . As such, form and function in rickettsiae are closely similar to form and function found in their free-living counterparts . This review of rickettsiae as bacteria portrays the broad similarities of rickettsiae and free-living bacteria, as well as the differences which distinquish one group from the other and one rickettsia from another . Growth characteristics and requirements, ecologic influences, special adaptations, antibiotic susceptibilities and host-parasite relationships will be considered in a broad survey of likenesses and differences displayed by rickettsiae pathogenic to man.

J UOEH, 1985 Sep 1, 7(3), 291 - 7
{Serum type III procollagen peptide in diagnosis of lung fibrosis due to silicosis and bleomycin toxicity}; Okuno F et al.; Early diagnosis of lung fibrosis has been hampered by the lack of a simple, convenient and specific test . Measurement of serum type III procollagen peptide (Pro (III)-N-P) by the method originally developed by Rohde et al . has been shown to be useful for the evaluation of hepatic fibrosis . The present study, therefore, was carried out to investigate the usefulness of the measurement of Pro (III)-N-P in 24 patients with lung fibrosis due to silicosis, and in 7 patients with malignant lymphoma treated with bleomycin, antitumor antibiotic which was the adverse effect of producing fibrosis in the lung . The normal value of the peptide in adults was 8.60 +/- 2.35 ng/ml (mean +/- SD; n = 68) and the normal upper level was set at 13.4 ng/ml (mean +/- 2SD) . Patients with silicosis had significantly but not extremely high levels of the peptide and 25% of the patients showed abnormally high values . The level of Pro (III)-N-P was associated with neither physical findings, chest X-p findings nor pulmonary function test results . Three of 7 patients showed increased levels during treatment with bleomycin . In one case, a total dose of 120 mg of bleomycin for over a period of 14 months markedly increased the level of the peptide . These observations suggest that the determination of Pro (III)-N-P may be useful for the detection of lung fibrosis.

J Antibiot (Tokyo), 1985 Sep, 38(9), 1257 - 65
Mechanisms affecting peplomycin sensitivity of Chinese hamster cell lines; Ozawa S et al.; Chinese hamster lung cell line V79 was ca . 13 times more resistant to peplomycin (PEP), and 6 times more resistant to bleomycin (BLM)-A2 than Chinese hamster ovary (CHO) cell line . The natural resistance of V79 cells to PEP or BLM was attributed to higher levels of BLM hydrolase activity and lower cellular uptake of the antibiotic . The sensitivity to PEP of a mutant clone CHO/O-2 T-1 was similar to that of CHO . A hybrid clone of CHO/O-2 T-1 X V79 showed an intermediate sensitivity to PEP between those of both parental cell lines, suggesting that the gene responsible for the natural resistance to PEP appears codominantly in the hybrid . The BLM hydrolase activity of the hybrid was also found intermediate between those of both parental cells . Mutant clones CHO/O-2 T-5 and CHO/O-2 T-6 were 8.3-9.0 times more sensitive to PEP than CHO cells . Hybrid clones CHO/O-2 T-5 X V79 and CHO/O-2 T-6 X V79 displayed PEP sensitivity similar to that of V79, suggesting that the gene responsible for the PEP supersensitivity (PEPss) behaves recessively in the hybrids . Both PEPss clones showed levels of BLM hydrolase and cellular uptake of {3H}PEP similar to the parental CHO cells, suggesting that the PEPss is due to neither BLM hydrolase nor cellular uptake of the antibiotic . Increased PEP-induced DNA cleavage and decreased DNA repair in the PEPss clones were demonstrated by alkaline sucrose density gradient sedimentation method . The results suggest that the PEPss of these mutant clones is attributed to decreased DNA-repairing activity and/or increased DNA-breaking activity.

Biochem J, 1985 Sep 1, 230(2), 557 - 60
The action of actinomycin D on the transcription of T7 coliphage DNA by Escherichia coli RNA polymerase; Flamee PA; An actinomycin D molecule bound to DNA sometimes stops the synthesis of RNA by Escherichia coli RNA polymerase . However, quite often, the bound antibiotic is released before the RNA polymerase detaches from the template DNA, so that the enzyme can resume, without interruption, the synthesis of the RNA chain.

S Afr Med J, 1985 Aug 31, 68(5), 335 - 6
Rectal spirochaetosis--symptomatic response to metronidazole and mebendazole . A case report; Burns DG et al.; A white homosexual man presented with a 6-week history of intermittent diarrhoea, abdominal pain, nausea and malaise . Threadworm infestation was present, but other gastro-intestinal infection was excluded . Rectal spirochaetosis was found on examination of a rectal biopsy specimen . The patient's symptoms disappeared and the rectal tissue returned to normal on biopsy after treatment with metronidazole and mebendazole . It is suggested that the symptoms were directly related to the presence of rectal spirochaetosis, which responded to the antibiotic.

J Biol Chem, 1985 Aug 25, 260(18), 10326 - 31
Localization of sites of photoaffinity labeling of the large subunit of Escherichia coli ribosomes by arylazide derivative of puromycin; Olson HM et al.; Previous work (Nicholson, A . W., Hall, C . C., Strycharz, W . A., and Cooperman, B . S . (1982) Biochemistry 21, 3797-3808) showed that {3H}p-azidopuromycin photoaffinity labeled 70 S Escherichia coli ribosomes and that photoincorporation into 50 S subunit proteins was in the order L23 greater than L18/22 greater than L15 . In the present work we report on immunoelectron microscopic studies of the complexes formed by p-azidopuromycin-modified 50 S subunits with antibodies to the N6,N6-dimethyladenosine moiety of the antibiotic . The p-azidopuromycin-modified 50 S subunits appear to be identical to unmodified control subunits in electron micrographs . Complexes of modified subunits with antibodies to the N6,N6-dimethyladenosine moiety of p-azidopuromycin were visualized in micrographs . Individual subunits with a single bound antibody (monomeric complexes) and pairs of subunits cross-linked by a single antibody (dimeric complexes) were separately evaluated and showed similar results . Two regions of p-azidopuromycin photoincorporation were identified . The primary site, seen in about 75% of the complexes, is between the central protuberance and small projection, on the side away from the L7/L12 arm, in a region thought to contain the peptidyltransferase center . The secondary site, of unknown significance, is at the base of the subunit maximally distant from the arm . These placements are essentially identical to those we observed in analyses of puromycin photoincorporation (Olson, H . M., Grant, P . G., Cooperman, B . S., and Glitz, D . G . (1982) J . Biol . Chem . 257, 2649-2656) and quantitatively similar to evaluations of monomeric puromycin-50 S subunit complexes . The data support the placement of proteins L23, L18/22, and L15 at or near the peptidyltransferase center at the primary site and suggest, in addition, that the secondary site includes a genuine area of puromycin affinity.

Biochim Biophys Acta, 1985 Aug 16, 841(2), 145 - 50
2'(3')-O-L-Phenylalanyl derivatives of N2,5'-anhydroformycin and N4,5'-anhydroformycin: new substrates for ribosomal peptidyltransferase with a fixed anti and syn conformation of the base; Bhuta P et al.; The 2'(3')-O-L-phenylalanyl-N2,5'-anhydroformycin (1c) and 2'(3')-O-L-phenylalanyl-N4,5'-anhydroformycin (2c), obtained by chemical synthesis, are substrates for ribosomal peptidyltransferase from Escherichia coli . Nucleoside 1c, which mimics an anti conformation of antibiotic formycin, has 80% of the acceptor activity of puromycin at 5 x 10(-4) M determined by the release of N-Ac-Phe residue from the 70 S ribosome-poly(U)-N-Ac-{14C}Phe-tRNA complex . The reaction product, 2'(3')-O-(N-acetyl)-L-phenylalanyl-L-phenylalanyl-N2,5'-anhydroformyc in (1d), was characterized by paper electrophoresis before and after alkaline hydrolysis . By contrast, nucleoside 2c, which resembles a syn conformation of formycin, exhibited only 20% of the acceptor activity of puromycin at 5 x 10(-4) M . The results which are in accord with previous models have shown that a substrate with its base in an anti conformation is preferable for the acceptor site of peptidyltransferase than the corresponding syn counterpart . Nevertheless, it is possible that an intermediate conformation, for example, high anti (amphi-minus), is an optimal arrangement for acceptor site substrates.

Nucleic Acids Res, 1985 Aug 12, 13(15), 5563 - 84
Interspersed repetitive and tandemly repetitive sequences are differentially represented in extrachromosomal covalently closed circular DNA of human diploid fibroblasts; Riabowol K et al.; Extrachromosomal covalently closed circular DNA (cccDNA) was isolated from human diploid fibroblasts by alkaline denaturation/renaturation and CsCl-ethidium bromide isopycnic centrifugation . Probing across these gradient fractions showed a higher proportion of cccDNA sequences homologous to the interspersed highly repetitive Alu I and Kpn I sequences than to the human tandemly-repetitive Eco RI (alphoid) DNA . Cloning of these cccDNAs was then carried out following digestion with restriction endonucleases Hind III, Bam HI or Pst I, and ligation into plasmid pBR322 . Many isolated recombinant clones were unstable as seen by a high rate of loss over four cycles of antibiotic selection, and frequent plasmid modifications including deletions adjoining the site of insertion . Of 107 cloned sequences which appeared relatively stable, i.e., survived four cycles of antibiotic selection without incurring detectable deletions, 28% and 11% showed homology to Alu I and Kpn I families, respectively, while 4% contained sequences homologous to both . In contrast, less than one percent hybridized to probes for tandemly-repetitive sequences, Eco RI and Satellite III . The average insert size of cloned cccDNA derived from human fibroblasts, 2.52 Kbp, was larger than previously reported for similar clones derived from genetically less stable permanent lines, which may reflect differences in the process of cccDNA generation.

Am J Med, 1985 Aug 9, 79(2A), 110 - 3
Aspects of clinical trials with ceftazidime worldwide; Foord RD; Overall results from worldwide clinical studies of ceftazidime in open and comparative trials conducted over a four-year period in North America, Europe, and elsewhere are presented . Data from 3,570 patients treated with ceftazidime in open studies and from 1,340 patients receiving ceftazidime and 1,180 patients receiving other antibiotics in comparative studies are discussed . The comparative antibiotics consisted of aminoglycosides alone in 14.2 percent of patients, aminoglycosides combined with one or two beta-lactams in 43 percent, beta-lactams alone in 34 percent, and other antibiotic combinations in 8.8 percent . In comparative studies, bacterial clearance rates were 80.6 percent for ceftazidime and 72.5 percent for other antibiotics . Clinically, 92.6 percent of the infected sites in ceftazidime-treated patients in open studies were cured or improved, and 91.1 percent were cured or improved in comparative studies; 84.8 percent of the infected sites were cured or improved in patients treated with other antibiotics . Data indicate that ceftazidime monotherapy is as effective as combination antibiotic therapy in the empiric treatment of febrile non-neutropenic patients . The role of ceftazidime monotherapy in the treatment of febrile neutropenic patients is not yet firmly established . Superinfections were reported in 2.6 percent of the patients treated with ceftazidime alone in open trials, in 4.2 percent of the patients treated with ceftazidime alone in comparative trials, and in 8.5 percent of the patients treated with other antibiotics . During treatment, the sensitivity of bacteria to ceftazidime decreased in 2.5 percent of the pathogens isolated . Adverse events occurred in 10.2 percent of patients treated with ceftazidime in open studies, in 8.4 percent of those treated with ceftazidime in comparative studies, and in 8.8 percent of those treated with other antibiotics . The adverse events in both ceftazidime- and control-treated patients were thought by the investigators to be drug-related in about 40 percent of cases, not drug-related in 20 percent of cases, and of unknown etiology in the remaining cases.

Jpn J Antibiot, 1985 Aug, 38(8), 2374 - 8
{Fundamental and clinical studies of cefpiramide in the field of obstetrics and gynecology}; Shintani M et al.; Cefpiramide (CPM, SM-1652), a new cephem antibiotic, was fundamentally and clinically studied . The following results were obtained . Serum and internal genital tissue levels of CPM were measured following intravenous drip infusion of 1 g . High serum levels of 30 micrograms/ml and tissue levels of more than 4 micrograms/g were at least maintained for 8 hours . Favourable transfer of CPM into the pelvic dead space exudate was observed . The exudate level was 7.25 micrograms/ml on average even at 8 hours after intravenous drip infusion . A total of 6 cases comprising 4 with Bartholin's cyst, 1 with pelvic peritonitis and 1 with lymphocyst was treated with CPM at a dose of 0.5-2 g twice daily by intravenous injection or intravenous drip infusion . The clinical response was excellent in 1 case and good in 5 cases . Side effects and abnormal laboratory findings due to the drug were not noted.

Anat Rec, 1985 Aug, 212(4), 358 - 63
Filipin-sterol complexes in the plasma membrane of zebrafish spermatozoa; Kessel RG et al.; The presence and distribution of filipin-sterol complexes in the plasma membrane of zebrafish (Brachydanio rerio) sperm was investigated . The zebrafish sperm plasma membrane, treated with freeze-fracture techniques, is seen to contain a multitude of intramembranous particles that, in a specific region of the posterior part of the sperm head, are organized into unusual particle arrays that appear as simple hexagons or parallelograms . The polyene antibiotic filipin forms complexes with 3-beta-OH sterols to produce characteristic protrusions and pits in membranes that are readily observable in freeze-fracture replicas . Numerous filipin-sterol complexes were found to populate the sperm plasma membrane, and the complexes exhibited variability in their distribution in different sperm . This appears to be the first illustrated example of an acrosomeless sperm that exhibits a high concentration of filipin-sterol complexes . In contrast, the unique grating formed by the intramembranous particles as well as variable amounts of membrane surrounding the unusual particle arrays were always free of the filipin-sterol complexes . Thus, while cholesterol appears to be present in the plasma membrane of the zebrafish sperm, it is not apparent in the highly differentiated region of the membrane based on the observed distribution of the filipin-sterol complexes.

J Gen Microbiol, 1985 Aug, 131 ( Pt 8), 1999 - 2005
Mechanism of self-protection in a puromycin-producing micro-organism; Sugiyama M et al.; Puromycin is a potent inhibitor of bacterial protein synthesis, but puromycin-producing Streptomyces alboniger KCC S-0309 is tolerant to the antibiotic in vivo . Puromycin bound to both 30S and 50S ribosomal subunits from S . alboniger and inhibited polyuridylate-directed polyphenylalanine synthesis by the ribosomes . However, the organism possessed a novel puromycin-inactivating enzyme which acetylated the antibiotic at the 2''-NH2 group of the O-methyltyrosine moiety.

J Pediatr Surg, 1985 Aug, 20(4), 402 - 5
Subclavian Broviac catheters in children--technical considerations in 146 consecutive placements; Gauderer MW et al.; During a 42-month span, 146 subclavian Broviac type catheters were placed in 129 children . In an additional 6 patients, a venotomy was necessary for successful cannulation, bringing the total number of attempts to 152 . Indications were: parenteral nutrition (78), chemotherapy/bone marrow transplant (54), longterm antibiotic or other medication administration (14) . Fifty-two were under 1 year of age . Forty-one weighed less than 5 kg and 7 were under 1 kg . Thirty-five had previous central lines (subclavian Broviacs--15) . Additional procedures were common (31) . Eight had thrombocytopenia . Insertion related problems were inability to cannulate vein--6 (3.9%) . All had successful catheter placement by cut down . Over five punctures--27 (17.7%) . Initially misdirected catheters--13 (8.9%) and, Arterial puncture--four (2.6%) . Complications were pneumothorax--two . Tube thoracostomy required in one (650 g) . Subclavian vein thrombosis after unsuccessful cannulation--one (1500 g) . Questionable phrenic nerve injury--one (900 g) . Transient venous occlusion of left arm--one (650 g) . Accidental catheter damage--two; and air embolization without consequences, perioperative catheter clotting, and hematoma of tract occurred once each . There was no catheter-related mortality . Because the only complications producing untoward sequelae were in very small infants, our present recommendation is that if successful cannulation of the subclavian is not possible with the first few passages of the needle, a cut-down insertion is preferred in this group . Our experience indicates that subclavian indwelling central catheter placement in the pediatric population can be accomplished with a low morbidity.

J Chir (Paris), 1985 Aug-Sep, 122(8-9), 447 - 54
{Peritoneal complications during continuous ambulatory peritoneal dialysis: surgical aspects}; Midy D et al.; The principal complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis in most cases benign and treated effectively by local, specific antibiotic therapy . In some cases, however, the infection fails to respond to medical treatment and surgical exploration occasionally reveals serious lesions such as sclerosing peritonitis or an intestinal perforation . Prognosis is dependent not only on the extent and severity of the lesion but also on the rapidity of operative intervention . The development of an appendicitis, often masked by early antibiotic therapy, represents a particular course of peritoneal infection during CAPD.

Cesk Gynekol, 1985 Aug, 50(7), 490 - 2
{Actinomycoses of the female genitalia in connection with IUD insertion}; Kresnicka J et al.; PIP: Abdominal actinomycoses with genital localization are relatively rare, but their occurrence has been increasing recently due to more extensive use of IUDs . After a brief review of the etiology, diagnosis, and treatment of this disease, 3 cases of IUD-induced genital actinomycosis are described . All 3 women were in their 40s . In 2 cases, the disease developed within a week after the IUD had been extracted . The patients were hospitalized with a diagnosis of adnexitis, which was confirmed by histological tests, anaerobic cultures, and microscopic examination . In all 3 cases, surgery was followed by antibiotic therapy with megadoses of crystalline PNC, Entisol, and subsequent long-term treatment with ampicillin . The treatment was successful; the women recovered to an almost normal gynecological condition .

Can J Ophthalmol, 1985 Aug, 20(5), 171 - 5
Intraocular penetration of netilmicin; Orr WM et al.; The intraocular penetration of the aminoglycoside netilmicin following intramuscular and subconjunctival injection was studied in 102 patients undergoing elective cataract surgery . Those who received either a single 1.5-mg/kg intramuscular injection or two 1.5-mg/kg injections 6 hours apart subsequently had therapeutic serum levels but aqueous levels of less than 2.4 micrograms/mL . Those who received a subconjunctival injection of either 12.5 or 25 mg of netilmicin subsequently had aqueous levels of up to 36 or 85.6 micrograms/mL; therapeutic levels in the anterior chamber persisted for 7 to 9 hours, with higher levels following the 25-mg injection . Despite wide variation in the aqueous levels following subconjunctival injection the ocular penetration of netilmicin was comparable to that reported for other aminoglycosides . No major complications were associated with the use of this antibiotic by either route.

J Infect Dis, 1985 Aug, 152(2), 344 - 50
Acute myocardial effects of chloramphenicol in newborn pigs: a possible insight into the gray baby syndrome; Werner JC et al.; Mechanical function and mitochondrial respiration were observed in newborn pig hearts in the presence of chloramphenicol . Isolated perfused hearts exposed to chloramphenicol (25, 50, or 100 micrograms/ml) demonstrated acute reductions in pressure development and cardiac output accompanied by elevated left atrial filling pressure . The effects of chloramphenicol and chloramphenicol succinate (25, 50, 100, or 200 micrograms/ml) on oxidative activity of isolated mitochondria were also investigated . With unesterified chloramphenicol, inhibition of state 3 respiration was most apparent when glutamate and palmitylcarnitine were supplied as substrates . Inhibition of mitochondrial oxidation of succinate or glutamate was only detectable at 200 micrograms/ml . Inhibition of alpha-ketoglutarate oxidation was not seen at any concentration of antibiotic studied . Chloramphenicol succinate most strongly inhibited state 3 oxidation of succinate and alpha-ketoglutarate and had relatively mild effects on oxidation of glutamate and palmitylcarnitine . Succinate oxidation by submitochondrial particles was unaffected by chloramphenicol succinate, a result suggesting interference with succinate transport.

Arch Intern Med, 1985 Aug, 145(8), 1435 - 7
Adult respiratory distress syndrome secondary to tularemia pneumonia; Sunderrajan EV et al.; Three patients with tularemia pneumonia developed adult respiratory distress syndrome and required positive end-expiratory pressure for adequate oxygenation . Rapid improvement was noted following appropriate antibiotic therapy, and mechanical ventilation was successfully discontinued after six to eight days.

Am J Surg, 1985 Aug, 150(2), 275 - 6
Repair of long-term venous catheters; Leider ZL et al.; The insertion of long-term Silastic catheters into the vena cava for home parenteral nutrition, antibiotic administration, and chemotherapy is increasing; however, one of the often described complications of these catheters is breakage of the external segment of the catheter . A new device as well as a new method for repair of the catheter has been described . Clinical testing of the catheters repaired with this device by our nutritional support service has demonstrated no leakage or occlusion at the catheter repair site . We believe the catheter repair kit described is simpler to use than the repair kit currently on the market.

Am J Obstet Gynecol, 1985 Aug 1, 152(7 Pt 2), 935 - 9
Classification and pathogenesis of vulvovaginal candidiasis; Monif GR; Although candidiasis of the female genital tract is one of the most common of the vaginitides, it is a poorly understood disease entity . Vulvovaginal candidiasis is a monoetiologic disease, but the pathways by which pathogenic expression is attained are sufficiently divergent to constitute a classification schema that influences therapy . For selection of appropriate therapy, the following three broad categories are proposed: (1) primary candidiasis, (2) antibiotic-induced candidiasis, and (3) systemically induced candidiasis.

Pediatrics, 1985 Aug, 76(2), 172 - 5
Medical management of congenital nasolacrimal duct obstruction; Nelson LB et al.; A consecutive series of 113 infants seen with congenital nasolacrimal duct obstruction were treated with local massage and topical antibiotic ointment . In 107 of the infants the obstruction was resolved within 8 months of initiation of this form of management . Nearly all of the infants were spared a surgical procedure that probably would have been performed if early probing of the nasolacrimal system had been advocated.

J Fam Pract, 1985 Aug, 21(2), 117 - 22
Characteristics and management of febrile young children seen in a university family practice; Soman M; A cohort of 311 children registered with the University of Washington Family Medical Center was retrospectively identified and followed until the age of 2 years . Analysis of all encounters for which a temperature of 37.7 degrees C (100 degrees F) or above was noted revealed 438 such encounters among 189 patients . Only 30 encounters involved patients aged under 3 months, and in 74 percent of the encounters the temperature was below 38.9 degrees C (102 degrees F) . The most common diagnoses were otitis media (34 percent), upper respiratory tract infection (19 percent), fever without a source (14 percent), and acute gastroenteritis (7 percent) . While antibiotic usage, follow-up, and laboratory utilization all increased with increasing temperature, the latter was unrelated to a child's age . Laboratory evaluation of children considered at high risk for occult illness did not adhere to published guidelines . A more aggressive laboratory approach is recommended for such children, as is follow-up contact . Further studies to evaluate the risk of occult illnesses in febrile children seen in family medicine settings would be helpful in refining and improving management strategies in these settings.

Appl Environ Microbiol, 1985 Aug, 50(2), 438 - 40
Possible role of streptomycin released from spore cell wall of Streptomyces griseus; Szabo I et al.; Vegetative mycelia and spores of the investigated high- and low-producer strains of Streptomyces griseus bound significant amounts (4%) of streptomycin, which could be removed by increasing ionic strength . The release of antibiotic from the spores was easier when the spores were germinating . This phenomenon is considered to play an ecological role . We suppose that the streptomycin released during the germination process may protect the young hyphae from the different bacteria growing in the microenvironment of the Streptomyces spores.

Jpn J Cancer Res, 1985 Aug, 76(8), 672 - 5
Screening of agents which convert 'transformed morphology' of Rous sarcoma virus-infected rat kidney cells to 'normal morphology': identification of an active agent as herbimycin and its inhibition of intracellular src kinase; Uehara Y et al.; During the course of screening of agents active in converting the transformed morphology of Rous sarcoma virus-infected rat kidney cells to the normal morphology, we identified an active substance produced by Streptomyces sp . MH237-CF8 as herbimycin . Herbimycin converted almost all cells into the normal morphology . The antibiotic was found to be an inhibitor of p60src-associated protein kinase in the cells.

Cancer Res, 1985 Aug, 45(8), 3510 - 6
Interactions of mitomycin C with mammalian DNA detected by alkaline elution; Dorr RT et al.; The antitumor antibiotic mitomycin C (MMC) was studied in vitro using L1210 leukemia and 8226 human myeloma cells . Cytotoxicity was evaluated by colony formation in soft agar, and DNA damage was analyzed using alkaline elution filter assays . The purposes of these studies were: (a) to characterize the time course of MMC-DNA damage; (b) to characterize the type of DNA damage {DNA-DNA interstrand cross-links (ISC), DNA-protein cross-links (DPC), single and double strand breaks (SSBs, DSBs)}; and (c) to correlate this damage with cytotoxicity in vitro . Colony-forming assays showed the D0 value for 1 h MMC to be 15.0 microM for L1210 cells and 17 microM for 8226 cells . Alkaline elution studies showed that dose-dependent ISCs and DPCs formed rapidly following MMC exposure . Removal of cross-links was delayed, with only 50% repaired 32 h after exposure . There was a good correlation between ISCs and cytotoxicity in dose-response studies in each cell line . ISCs appeared to comprise most of the MMC-DNA lesions in both cell lines . No DNA SSBs or DSBs were observed following MMC exposure . Nuclei isolated from both cell lines and exposed to MMC produced less MMC alkylation than whole cells but, again, no strand breaks were evident . These results demonstrate that MMC is principally an alkylating agent when used at pharmacological (cytotoxic) concentrations in vitro . The lack of evidence for DNA strand breaks discounts a significant role for putative quinone-generated oxygen free radicals in the production of MMC cytotoxicity.

Jpn J Antibiot, 1985 Aug, 38(8), 2379 - 83
{Fundamental and clinical studies on cefpiramide in the field of obstetrics and gynecology}; Hirabayashi K et al.; Cefpiramide (SM-1652, CPM), a new cephem antibiotic was studied for the transfer into intrapelvic tissues and clinical efficacy in the field of obstetrics and gynecology . The results were obtained as follows . Clinical results of 17 patients with obstetrical and gynecological infection were excellent in 10 cases, good in 6, and poor in 1 with the efficacy rate of 94.1% . Following a single intravenous 30 minutes-drip infusion of 1 g dose of CPM, the peak of serum level and intrapelvic tissues were obtained at 30-60 minutes after completion of the administration . No adverse reaction or abnormal laboratory findings were observed.

J Antimicrob Chemother, 1985 Aug, 16(2), 261 - 5
The penetration of ceftazidime into peritoneal fluid in patients undergoing elective abdominal surgery; Corbett CR et al.; Using paper discs we have made repeated observations during laparotomy in 31 patients after giving 1 g of ceftazidime intravenously . Samples of serum were obtained simultaneously . Rapid transfer of antibiotic occurred . Peak concentration in peritoneal fluid occurred within 10 minutes of injection (66.7 mg/l, S.E . +/- 10.6), the concurrent mean serum level being 106.0 mg/l (S.E . +/- 10.7) . Thereafter levels in serum and peritoneal fluid fell roughly in parallel.

Antimicrob Agents Chemother, 1985 Aug, 28(2), 293 - 8
Moxalactam kinetics during continuous ambulatory peritoneal dialysis after intraperitoneal administration; Jones TE et al.; Moxalactam kinetics during continuous ambulatory peritoneal dialysis (CAPD) was followed in eight patients after a single intraperitoneal dose of 1 g . Approximately 60% of the dose was absorbed after a dwell time of 4 h . Dialysis solutions were exchanged at 4-h intervals with an overnight dwell of 8 h . The mean (+/- standard deviation) elimination half-life was 13.2 +/- 2.9 h, and the mean apparent volume of distribution was 0.22 +/- 0.08 liters/kg . Mean total clearance was 11.5 +/- 2.4 ml/min, with a mean dialysis clearance of 2.3 +/- 0.5 ml/min . The maximum concentration in plasma ranged from 24.5 to 54.1 micrograms/ml . Moxalactam concentrations in the peritoneal dialysis fluid were above 80 micrograms/ml during the first exchange and above 2 micrograms/ml for a further three exchanges . A suggested intraperitoneal dose regimen for patients undergoing CAPD is 1 g initially, followed by 15 to 25% of the recommended dose for normal patients given at the same time intervals, or 30 to 50% of the recommended dose at twice the usual intervals . Moxalactam is suggested for initial treatment of peritonitis in CAPD patients who do not have ready access to the antibiotic of choice.

Mol Cell Biol, 1985 Aug, 5(8), 1918 - 24
Neomycin resistance as a dominant selectable marker for selection and isolation of vaccinia virus recombinants; Franke CA et al.; The antibiotic G418 was shown to be an effective inhibitor of vaccinia virus replication when an appropriate concentration of it was added to cell monolayers 48 h before infection . Genetic engineering techniques were used in concert with DNA transfection protocols to construct vaccinia virus recombinants containing the neomycin resistance gene (neo) from transposon Tn5 . These recombinants contained the neo gene linked in either the correct or incorrect orientation relative to the vaccinia virus 7.5-kilodalton gene promoter which is expressed constitutively throughout the course of infection . The vaccinia virus recombinant containing the chimeric neo gene in the proper orientation was able to grow and form plaques in the presence of G418, whereas both the wild-type and the recombinant virus with the neo gene in the opposite polarity were inhibited by more than 98% . The effect of G418 on virus growth may be mediated at least in part by selective inhibition of the synthesis of a subset of late viral proteins . These results are discussed with reference to using this system, the conferral of resistance to G418 with neo as a positive selectable marker, to facilitate constructing vaccinia virus recombinants which contain foreign genes of interest.

Am J Clin Oncol, 1985 Aug, 8(4), 298 - 301
Phase II evaluation of aclacinomycin-A in patients with adenocarcinoma and large cell carcinoma of the lung; Tapazoglou E et al.; Aclacinomycin-A (ACLA-A), the new anthracycline antibiotic that produces substantially less cardiotoxicity relative to doxorubicin, was evaluated in a phase II trial for advanced large cell and adenocarcinoma of the lung patients . Twenty-three patients with measurable disease were entered into the trial and received ACLA-A in doses of a weekly infusion of 65 mg/m2 and 85 mg/m2 . Eighteen patients were evaluable for response and toxicity . Two patients were evaluable for toxicity only, one died before completion of a full course of therapy, and two did not receive the drug . There were no complete or partial remissions in this study . Three patients had disease stabilization for a median of 10 weeks (range 6-17) . Toxicity was mainly hematologic . Nausea and vomiting were moderate . ACLA-A, in the dose schedules used, appears to have no activity in large cell and adenocarcinoma of the lung.

Immunopharmacology, 1985 Aug, 10(1), 19 - 25
Aclacinomycin-A inhibits the development and the expression of suppressor cell activity to contact sensitivity; Andrade-Mena CE et al.; Aclacinomycin-A, a cytotoxic antibiotic, is capable of inhibiting the development and expression of suppressor cell activity for the contact sensitivity reaction to picryl chloride elicited by two intravenous injections of 3.5 mg picryl sulfonic acid when given as a single dose of 4 mg/kg 2 or 4 days before the first or 1 or 3 days after the second injection of picryl sulfonic acid . This inhibition may occur because aclacinomycin-A inhibits the development and expression of both suppressor T-cells and their precursors . In addition, it is shown that aclacinomycin-A diminishes the capacity of spleen T-cells from picryl sulfonic acid-injected mice to inhibit upon adoptive transfer the contact sensitivity reaction to picryl chloride of normal and presensitized animals.

Chem Biol Interact, 1985 Aug-Sep, 54(3), 337 - 48
The modulation of ion channels by the inhalation general anaesthetics . A1H-NMR investigation using unilamellar phospholipid membranes; Veiro JA et al.; The modulation of a variety of mechanisms of channel-mediated transport across unilamellar phospholipid membranes by a range of halogenated inhalation general anaesthetics (chloroform, enflurane, halothane and methoxyflurane) was investigated using 1H-NMR spectroscopy . Transport of the probe ion Pr3+ across egg yolk phosphatidylcholine (PC) and dipalmitoyl phosphatidylcholine (DPPC) vesicular membranes in the presence of the channel forming polypeptides alamethicin 30 and melittin, and the polyene antibiotic nystatin, as well as the degree of vesicular lysis at the gel to liquid-crystal phase transition of DPPC vesicles was monitored . The observation that the inhalation general anaesthetics inhibit such membrane permeability independently of the channel system or type of lipid used, suggests that hydrogen-bonded water structure and/or hydrogen-bonding centres at dipolar lipid-polypeptide interfaces, can be likely sites of action of the general anaesthetics.

Am J Med, 1985 Aug, 79(2), 263 - 7
Severe pulmonary hypertension in a patient with Whipple's disease; Morrison DA et al.; Rapidly progressive heart failure, in part related to severe pulmonary hypertension, developed in a patient with biopsy-proved Whipple's disease . The patient's pulmonary hypertension progressed despite antibiotic therapy and histologic remission of his intestinal disease . The combination of oral nifedipine and low-flow continuous oxygen led to both short- and long-term increases of at least 2 liters per minute in cardiac output and reductions of more than 10 mm Hg in mean pulmonary artery pressure . Accompanying these hemodynamic changes was an improvement of more than 10 percent in right ventricular ejection fraction . The relationship between this patient's pulmonary hypertension and his Whipple's disease is not known.

Brain Res, 1985 Jul 29, 339(2), 382 - 5
Systemic hypoglycemia following central injection of endotoxin in mice; Amir S et al.; Intracerebroventricular microinjection of endotoxin in mice resulted in powerful hypoglycemia . The effect was reproduced by the biologically active moiety of endotoxin, lipid A, and prevented by coadministration of the polycationic peptide antibiotic polymyxin B (PMB) or by detoxification of endotoxin by means of mild alkaline hydrolysis . Central treatment with PMB also attenuated the hypoglycemic response to systemic administration of endotoxin or lipid A . These results suggest a direct role of the CNS in the mechanism of endotoxin hypoglycemia.

J Biol Chem, 1985 Jul 25, 260(15), 8771 - 6
Euglena gracilis chloroplast elongation factor Tu . Interaction with guanine nucleotides and aminoacyl-tRNA; Sreedharan SP et al.; The interaction of the chloroplast elongation factor Tu (EF-Tuchl) from Euglena gracilis with guanine nucleotides and aminoacyl-tRNA has been investigated . The apparent dissociation constant at 37 degrees C for the EF-Tuchl X GDP complex is about 3 X 10(-7) M and for the EF-Tuchl X GTP complex, it is about 1 order of magnitude higher . The sulfhydryl modifying reagent N-ethylmaleimide severely inhibits the polymerization activity of Euglena EF-Tuchl . In the presence of N-ethylmaleimide, the dissociation constant for the modified EF-Tuchl X GDP complex is increased by an order of magnitude . Conversely, both GDP and GTP protect EF-Tuchl from the modification . The polymerization activity of EF-Tuchl is also sensitive to the antibiotic kirromycin . In the presence of kirromycin, the apparent dissociation constant for the EF-Tuchl X GTP complex is lowered 10-fold . The interaction of aminoacyl-tRNA with EF-Tuchl was investigated by examining the ability of EF-Tuchl to prevent the spontaneous hydrolysis of Phe-tRNA and by gel filtration chromatography . The binding of aminoacyl-tRNA to EF-Tuchl occurs only in the presence of GTP indicating the formation of the ternary complex EF-Tuchl X GTP X Phe-tRNA . The effect of kirromycin on the interaction was also investigated . In the presence of kirromycin, no interaction between EF-Tuchl and Phe-tRNA is observed, even in the presence of GTP.

Biochim Biophys Acta, 1985 Jul 24, 825(3), 280 - 8
The accuracy of protein synthesis in reticulocyte and HeLa cell lysates; Luce MC et al.; The accuracy of translation in protein synthesis is measured as the rate of misincorporation of a particular amino acid, different from that specified by an mRNA codon, into protein . The cowpea variant of tobacco mosaic virus, CcTMV, contains no cysteine or methionine in its coat protein . Translation in vitro of purified CcTMV coat protein mRNA by rabbit reticulocyte and HeLa cell lysates has been performed . The coat protein product was purified by immunoprecipitation with specific antisera, and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The error rate was measured by comparing the incorporation of {35S}cysteine with incorporation of {3H}leucine, and the total CcTMV coat protein synthesized was calculated from its known leucine content . An error rate of (1-2) X 10(-3) cysteines/CcTMV coat protein was obtained with reticulocyte lysates . If errors were cysteine incorporation in place of arginine, this number is converted to 3 X 10(-4) cysteine/codon . If cysteine was incorporated anywhere in the polypeptide, the rate is 9 X 10(-6) cysteines/amino acid . The error frequencies with HeLa cell lysates were 6-fold higher . Paromomycin, a eukaryotic misreading antibiotic, increased error rates 10-fold in both lysates . These data compare well with in vivo measurements and suggest that some transformed cells may survive with higher mistranslation rates.

J Chromatogr, 1985 Jul 12, 342(1), 145 - 58
Determination of coumermycin A1 in plasma by reversed-phase high-performance liquid chromatographic analysis; Strojny N et al.; Coumermycin A1 is an antibiotic isolated from Streptomyces hazeliensis var . hazeliensis nov . sp . as a sodium salt which exhibits antistaphylococcal activity . A sensitive and selective high-performance liquid chromatographic method was developed for the determination of the compound and three known homologues which are extracted from plasma buffered to pH 6.5 into methyl-tert.-butyl ether-2-propanol (97.5:2.5), the residue of which is dissolved in the mobile phase and analyzed by automated reversed-phase high-performance liquid chromatography using UV detection at 330 nm for quantitation . Novobiocin is used as the internal standard . The method was used to determine the plasma concentration--time profile of coumermycin A1 in the dog following a single intravenous administration of a 12 mg/kg dose of a solubilized dosage form of the bulk drug substance.

S Afr Med J, 1985 Jul 6, 68(1), 46 - 8
Solitary abscess of the spleen . A report of 2 cases; Moosa MR et al.; Two cases of solitary abscess of the spleen are presented and illustrate the clinical setting and management of this potentially fatal condition . Both patients had presumed bacterial endocarditis with positive blood cultures yet failed to respond to appropriate antibiotic therapy . The clue to diagnosis was elevation of the left hemidaphragm . Outcome in each case was favourable after splenectomy.

Ann R Coll Surg Engl, 1985 Jul, 67(4), 227 - 8
Povidone-iodine bowel irrigation before resection of colorectal carcinoma; Parker MC et al.; Preoperative mechanical bowel preparation, peroperative topical antiseptic measures, and postoperative antibiotic therapy have all been shown to reduce infection after colorectal surgery . We report the results of a randomised trial of preoperative irrigation with a 10% aqueous solution of povidone-iodine (Betadine) versus water in patients undergoing major resection for large bowel carcinoma . All patients had mechanical bowel preparation, preoperative topical povidone-iodine and per and postoperative antibiotics . Of 22 study patients only one (4.6%) developed abdominal wound infection, whereas in 23 controls nine (39.1%) did so (P less than 0.01) . In three of the study patients cultures of swabs taken at operation from the transected bowel ends showed no bacterial growth . Arguably the bacterial population would have been markedly reduced in other patients . These results suggest that povidone-iodine irrigation before large bowel resection reduces wound sepsis.

J Antibiot (Tokyo), 1985 Jul, 38(7), 886 - 98
Synthesis and antitumor activity of spergualin analogues . I . Chemical modification of 7-guanidino-3-hydroxyacyl moiety; Umeda Y et al.; Many analogues and derivatives of an antitumor antibiotic, spergualin, were synthesized, and the relationships between the structure and the activity against mouse L-1210 tumor were studied . Both modification of the 15-hydroxyl group and alteration of chain-length of the omega-guanidinoacyl moiety affected the activity . 15-Deoxyspergualin (18, 1-amino-19-guanidino-11-hydroxy-4,9,12-triazanonadecane-10,13-d ion e) and its analogue 25 (1-amino-21-guanidino-11-hydroxy-4,9,12-triazauneicosane-10,13-dio ne) had strong activity, superior to that of spergualin.

Ophthalmology, 1985 Jul, 92(7), 938 - 46
Short- and long-term effects of postoperative corticosteroids on trabeculectomy; Starita RJ et al.; All patients with primary open-angle or primary angle-closure glaucoma requiring trabeculectomy between January 1982 and January 1983 were entered into a randomized prospective study to evaluate the effect of postoperative corticosteroids . Twenty-three eyes in Group 1 received a cycloplegic and topical antibiotic . Twenty-nine eyes in Group 2 received the same treatment, with the addition of topical 1% prednisolone acetate . Twenty-three eyes in Group 3 received the same treatment as Group 2, with the addition of systemic prednisone . Success rate was significantly improved with the use of topical corticosteroids . Systemic steroids did not prove to be of any added benefit over topical use alone.

Arch Otolaryngol, 1985 Jul, 111(7), 481 - 4
Laryngeal perichondritis and abscess; Souliere CR Jr et al.; Primary infection of the laryngeal cartilages has become rare in the antibiotic era . However, trauma, irradiation, a foreign body, or cancer may initiate the infection, particularly in the immunocompromised patient . We encountered three cases of perichondritis and abscess associated with airway intubation, nasogastric intubation, and external beam radiotherapy . Laryngeal perichondritis and abscess remain serious potential causes of laryngeal deformity and dysfunction.

Arch Biochem Biophys, 1985 Jul, 240(1), 121 - 7
Conversion of alpha-amino acids and peptides to nitriles and aldehydes by bromoperoxidase; Nieder M et al.; Pure bromoperoxidase from the marine alga, Penicillus capitatus, converts alpha-amino acids and peptides to the corresponding decarboxylated nitriles and aldehydes in the presence of hydrogen peroxide and bromide ion . Thus, both valine and valylvaline are converted to isobutyronitrile and isobutyraldehyde while alanine is converted to acetonitrile and acetaldehyde . The reaction is nonstereospecific and can be catalyzed by bromoperoxidases obtained from different sources . Bromoperoxidase catalyzes the conversion of methoxytyrosine to p-methoxyphenylacetonitrile . This reaction is consistent with the involvement of bromoperoxidase in the formation of aeroplysinin-1, a brominated aromatic nitrile antibiotic produced by a marine sponge.

Am Surg, 1985 Jul, 51(7), 418 - 22
Operative risks in patients with colorectal cancer; Irvin GL 3rd et al.; This study emphasizes the risks in the operative treatment of patients with colorectal cancer . In dissecting our overall operative mortality of 7.4 per cent in consecutive patients over a 5-year period, three factors influencing the outcome were identified . These were the age of the patient, the stage of the disease, and the availability of preoperative bowel preparation by mechanical cleansing and antibiotic suppression of the colonic bacterial flora . Earlier diagnosis and elective resection of prepared bowel offers marked improvement in the operative risk for patients with colorectal cancer.

Obstet Gynecol, 1985 Jul, 66(1), 59 - 62
Term maternal and neonatal complications of acute chorioamnionitis; Hauth JC et al.; One hundred and three women who developed acute chorioamnionitis at 37 weeks' gestation or beyond were studied retrospectively . Clinical findings included fever (99.2%), fetal (82%) and maternal (19.4%) tachycardia, uterine tenderness (16.5%), and foul-smelling amniotic fluid (8.7%) . Three of the 46 women who underwent cesarean section subsequently required addition of a second or third antibiotic for serious pelvic infection, whereas two had a subcutaneous wound infection requiring open drainage . Importantly, between zero and ten hours of the diagnosis of chorioamnionitis, a critical time interval where delivery impacted on neonatal infectious morbidity was not identified . Additionally, in the initial 24 hours after rupture of the fetal membranes there was no association between fetal, neonatal, or maternal complications versus duration of membrane rupture . These data suggest that immediate operative delivery of term gestations complicated by acute chorioamnionitis will not reduce neonatal morbidity.

J Nucl Med, 1985 Jul, 26(7), 718 - 21
Indium-111 chloride imaging in the detection of infected prostheses; Sayle BA et al.; Thirty-three patients with painful joint prostheses and a suspicion of infection were imaged with {111In}chloride . A final diagnosis was established by culture in 19 . Of these, 12 were categorized as true positives and three as true negatives . There were two false-positive studies, occurring in patients with knee prostheses . In both, the culture was obtained by aspiration . Two false negatives were in patients with hip prostheses, one of whom had been on long-term antibiotic suppressive therapy . The sensitivity was 86%, specificity 60%, and accuracy 79% . Seventeen of the proven cases had bone imaging prior to {111In}chloride imaging . All 17 static images were positive and were not helpful in differentiating loosening from infection . Using increased uptake on the blood-pool image as a criteria for infection, the sensitivity was 89%, but the specificity was 0 . Adding flow studies made little difference in interpreting the blood-pool images . This study shows that {111In}chloride accurate in evaluating infection in prosthesis than bone imaging.

J Neurosurg, 1985 Jul, 63(1), 131 - 3
Actinomycosis of the brain . Case report; He CW; A rare case of actinomycosis of the brain is reported . The patient recovered after surgical excision of the lesion and a prolonged course of antibiotic therapy . At follow-up examination 25 months later, the patient was in excellent health . Different types of actinomycotic infections of the central nervous system are reviewed and the diagnosis and treatment of this disease are discussed.

Exp Hematol, 1985 Jul, 13(6), 512 - 9
Amphotericin-B and monensin potentiation of murine erythropoiesis in vitro: a possible role for sodium ions; Tenaglia AN et al.; To study the role of monovalent cation flux in erythropoiesis we cultured mouse bone marrow cells with amphotericin B (AmB), monensin, valinomycin, or Etruscomycin . At low doses the polyene antibiotic AmB has been shown to increase cell permeability to Na+ and K+ and we found that it potentiated erythropoietin (epo)-stimulated erythroid-colony (CFU-E) and burst (BFU-E) growth at concentrations ranging from 0.5-1.0 micrograms/ml . Monensin, a sodium-specific ionophore, potentiated epo-stimulated erythroid growth at concentrations of 1-30 nM . On the other hand, a potassium-specific ionophore, valinomycin, did not cause potentiation, but rather suppressed epo-dependent colony formation . Etruscomycin, another polyene, but one which in mammalian cells increases ion permeability only at toxic concentrations, was also suppressive . Potentiating concentrations of AmB and monensin increased the sensitivity of CFU-E and BFU-E to epo and at saturating epo levels increased the numbers of erythroid colonies and bursts by about 40% . Neither AmB nor monensin stimulated erythroid growth in the absence of epo . We found a 20-fold difference in the AmB concentrations comprising the maximally potentiating dose in C57BL/6 and AKR marrow cultures . This is consistent with observed differences between these two mouse strains with regard to other effects of AmB on them, including the immunoadjuvant properties of AmB . Our results showing potentiation due to sodium ion flux may be related to previous work showing potentiation of erythroid differentiation caused by calcium ion flux, since sodium ion movement may directly affect the intracellular calcium ion concentration.

Mikrobiologiia, 1985 Jul-Aug, 54(4), 681 - 3
{Carbon dioxide fixation by the mycelium of the actinomycete Streptomyces chrysomallus var . macrotetrolidi}; Nefelova MV et al.; The mycelium of Streptomyces chryzomallus var . macrotetrolidi producing the macrotetrolide antibiotic nonactin was shown to be capable of carbon dioxide fixation . Carbon was found to be incorporated into nonactin and macromolecular compounds in the biomass . Carbon was incorporated within 20 to 40 min of the mycelium incubation with NaH14CO3 . Pyruvic and propionic acids stimulated carbon incorporation.

J Antimicrob Chemother, 1985 Jul, 16 Suppl A, 201 - 4
Autoradiography of tissue distribution of the IIA constituent of the pristinamycins; Aumercier M et al.; The tissue distribution of a radioactive analogue of the IIA constituent of the pristinamycins was studied in female mice by autoradiography . Examination of slides and photographs discloses the presence of the antibiotic on the skin and in the bone marrow only a short time after injection . Elimination of the antibiotic is quick and is mainly through the digestive tract.

J Antimicrob Chemother, 1985 Jul, 16 Suppl A, 151 - 66
Pharmacokinetics of macrolides, lincosamides and streptogramins; Osono T et al.; Macrolide antibiotics are known to be effective in spite of their low blood levels . This results in an exception to the customary rule of antibiotics evaluation, of judging the in-vivo effect of an antibiotic in terms of blood levels and MICs . Most efforts to improve blood levels of macrolides have been unsuccessful because of hepatic toxicity . Intravenous administration of macrolides has been difficult because of the frequent incidence of severe side effects . In the present paper, the in-vivo distribution characteristics and metabolic features of macrolides are summarized with some mention of those of lincosamides and streptogramins . Results show that macrolides are intrinsically toxic to man as a protein synthesis inhibitor, but that they are easily metabolized and destroyed in the body . In the course of this destruction, minute amount of a macrolide and its active metabolites distribute selectively in some tissues owing to their higher tissue affinity . Thus a delicate balance between tissue affinity and metabolism makes effective and safe oral therapy with minimum side activities.

Cell, 1985 Jul, 41(3), 727 - 34
Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo; Palacios R et al.; The continuously proliferating clones L/B AgA2, CB/Bm 7, Ba/C1, and Bc/Bm 11 were established from bone marrow of MRL/LPR, CBA/J, and BALB/c mice . These clones carry the B cell lineage surface antigen B-220 but not antigens normally expressed on mature B lymphocytes, myeloid cells, or T lymphocytes . Their immunoglobulin mu heavy chain and kappa light chain genes are in germ-line configuration . The G418 resistance gene was introduced into each clone with a retrovirus vector and then used as a selective marker for the progeny of transfected cells . Clones L/B AgA2, CB/Bm 7, and Bc/Bm 11, but not Ba/C1, could develop into antibody-secreting cells after in vivo transfer . None gave rise to cells responsive to polyclonal T cell activators, nor did any differentiate into cells that could develop into granulocyte/macrophage-colony-forming cells in vitro . All grew in interleukin 3 but not in other cytokines . We conclude that clones L/B AgA2, CB/Bm 7, and Bc/Bm 11 are early precursors of B lymphocytes.

Clin Radiol, 1985 Jul, 36(4), 437 - 9
Pulmonary sequestration: the value of ultrasound; Thind CR et al.; A child presented with a chest infection . A chest radiograph showed consolidation in the left lung base . This failed to clear in spite of adequate antibiotic therapy . Ultrasound examination (real-time) suggested pulmonary sequestration, and an aberrant blood supply was demonstrated . Subsequent angiography, surgery and pathological examination of the resected segment confirmed this.

J Gen Microbiol, 1985 Jul, 131 ( Pt 7), 1649 - 55
Fosfomycin-resistance plasmids determine an intracellular modification of fosfomycin; Leon J et al.; Escherichia coli cells carrying fosfomycin-resistance plasmids modify fosfomycin intracellularly . The product of this modification (fosfomycin-derivative) differs from fosfomycin in chromatographic mobility, but the chemical nature of the modification is not yet known . Fosfomycin-derivative appears to have a cytoplasmic location and lacks antibiotic activity . The modification system can be saturated by an excess of fosfomycin in the incubation media.

J Gen Microbiol, 1985 Jul, 131 ( Pt 7), 1639 - 47
Acriflavine-binding capacity controlled by the acrA gene of Escherichia coli; Nakamura H et al.; The acrA mutation in Escherichia coli led to a substantial increase of the acriflavine-binding capacity of the cell, whereas the related mutations acrB (gyrB) and arcC did not . Metal ions such as Na+, K+, Mg2+, Ca2+ and Al3+ effectively released the bound acriflavine, in proportion to their ionic strengths . The presence of cations, in fact, increased the survival fraction of the cells in the acriflavine-containing medium . Polymyxin B, an antibiotic which binds to membrane phospholipid, competed with acriflavine for binding sites . Cell wall digestion by treatment with lysozyme and EDTA slightly decreased the acriflavine-binding capacity . Almost no difference was observed in acriflavine-binding capacity between intact cells and cells from which lipopolysaccharide has been extracted (46.9% removed from the acrA cells and 47.4% from the acrA+ cells) . Acriflavine bound to the cells was most effectively extracted by ethanol containing 1% HCl or by 2% (w/v) SDS . The difference in the acriflavine-binding capacity between the acrA and acrA+ cells was also observed in the spheroplasts . These facts indicate a relationship between the acrA gene product and the acriflavine-binding capacity of the cells.

Toxicol Appl Pharmacol, 1985 Jul, 79(3), 412 - 22
Experimental systemic toxicology of 4'-epidoxorubicin, a new, less cardiotoxic anthracycline antitumor agent; Bertazzoli C et al.; The acute and chronic iv toxicity of 4'-epidoxorubicin, a new antitumor anthracycline antibiotic, was compared with doxorubicin . The LD50 of 4'-epidoxorubicin was 16.07 mg/kg in mice, 14.27 mg/kg in rats, and about 2 mg/kg in dogs; the LD50 of doxorubicin was 11.98 mg/kg in mice, 10.51 mg/kg in rats, and about 2.5 mg/kg in dogs . Rats and dogs were also dosed iv for 91 days (3 injections/week) with 4'-epidoxorubicin or doxorubicin at doses of 0.128, 0.32, and 0.8 mg/kg to rats and 0.064, 0.16, and 0.4 mg/kg to dogs . A comprehensive toxicological evaluation of the animals was carried out before, throughout, and at the end of the study . High-dose 4'-epidoxorubicin induced toxic clinical signs in dogs, and in both species caused loss of body weight, antiproliferative effects on blood-forming organs and testes, and degenerative lesions in kidneys and heart . The cardiac damage was moderate in rats and very mild in dogs; only three male rats died at this dose . The medium dose induced less pronounced changes and no heart lesions and the low dose was practically nontoxic . Doxorubicin showed similar antiproliferative activity, but more evident toxic effects, especially on the heart; many rats given the high dose died and some at the medium dose showed initial cardiac lesions . Thus 4'-epidoxorubicin appeared less toxic than doxorubicin; in particular cardiac damage was much less evident in animals chronically injected with the new drug.

J Prosthet Dent, 1985 Jul, 54(1), 13 - 5
Technique for cementation of provisional restorations; Campagni WV; A technique for cementation of a provisional resin splint or crown has been presented . The splint is lubricated with silicone grease and cemented with a noneugenol cement mixed with antibiotic ointment . The grease aids in the complete removal of the cement . The use of a sterile composite resin syringe and preloaded disposable tip allows delivery of the grease to the splint with minimal chance of bacterial cross contamination to the patient.

Infect Control, 1985 Jul, 6(7), 273 - 7
Evidence for the non-infectious etiology of early postoperative fever; Garibaldi RA et al.; In a prospective study of infections in 871 general surgery patients, we identified 81 patients who developed unexplained postoperative fevers . The majority of these episodes (72%) occurred early (within the first 48 hours) following surgery . Patients who developed early, unexplained fevers differed significantly from patients who developed documented postoperative infections . Patients with unexplained fevers were younger, had less severe underlying disease and underwent less extensive surgeries than patients who subsequently developed infections . In these respects, they were more similar to non-infected, non-febrile patients . We concluded that episodes of early, unexplained postoperative fever occur frequently in a wide range of general surgery patients . Most of these episodes are non-infectious in origin . Patients with early postoperative fevers should be evaluated to identify any obvious sources of infection . If no focus is identified, empiric antibiotic therapy should not be initiated nor should prophylactic antibiotics be extended for prolonged durations . Unexplained fevers will resolve in time without specific therapeutic interventions.

Antibiot Med Biotekhnol, 1985 Jul, 30(7), 529 - 32
{Natural and UV-induced variability of the producer of telavimycin Streptomyces levoris, Krass, strain 243}; Kandelaki ND et al.; The experimental data showed that the morphological variation of the culture of strain 243 of Streptomyces levoris, Krass, producing telavimycin (antibiotic 243) resulted in the formation of three morphological types differing in some features from the initial culture . Cultures of the type I and II colonies were most promising for selection . Strains producing higher yields of the antibiotic as compared to the initial strain 243 were selected from these cultures . After exposure of the spores of strain 243-96 to UV light in a dose of 500 erg/mm2 a highly productive strain 243-197 was isolated . The activity of this strain is 51 per cent higher than that of strain 243-96.

Antimicrob Agents Chemother, 1985 Jul, 28(1), 5 - 11
Directed biosynthesis of new saframycin derivatives with resting cells of Streptomyces lavendulae; Arai T et al.; Saframycin A is an antitumor antibiotic produced by Streptomyces lavendulae 314 which falls into the category of the N-heterocyclic quinone group . Biosynthetically the quinone ring is derived from two tyrosine molecules which condense to generate the basic ring system of saframycin A . The side chain also has been found to derive from two amino acids, i.e., glycine and alanine . Supplementation by various amino acid analogs of the side chain produced three new saframycin derivatives with a replaced side chain . These three saframycins, designated Yd-1, Yd-2, and Y3, contained 2-amino-n-butyric acid, glycine, and alanine residues, respectively . in place of the normal N-terminal pyruvic acid in the side chain of saframycin A . Feeding experiments with 13C-labeled dipeptide indicated that the amino acids are probably incorporated in the side chain as a dipeptide unit . It was also found that saframycin A is produced from saframycin Y3 by an enzymatic deamination reaction . Based on these results, saframycin biosynthesis in S . lavendulae is discussed.

Indian J Lepr, 1985 Jul-Sep, 57(3), 549 - 55
Clinical manifestations of iridocyclitis in leprosy; Suryawanshi N; Iridocyclitis--an inflammation of the iris and ciliary body occurs in lepromatous spectrum of leprosy of long duration . It is usually bilateral, has a very chronic course with acute exacerbations which are suppressed with the help of corticosteroids and other antiinflammatory drugs--Mydriatic to keep the Pupil dilated and also an antibiotic to take care of secondary infection which may be present . It is a major cause of blindness, due to its secondary damaging effects on the various ocular tissues . Medical and Paramedical Workers attending these patients must be made aware of the chronicity of the iridocyclitis so that regular referrals for examination of the eyes including slit lamp examination could be done and the activity of the disease and its complications detected early and treated . This chronic variety of iridocyclitis often gets less medical attention because of its insidious onset and minimal clinical signs in early stages, except by slit lamp examination . 57 patients suffering from iridocyclitis attending the ophthalmic department of S.L.R . & T.C . Karigiri were followed up carefully over a period of 2 1/2 years to study the clinical manifestations of iridocyclitis, it's complications and management.

Biochimie, 1985 Jul-Aug, 67(7-8), 887 - 915
Molecular recognition in noncovalent antitumor agent-DNA complexes: NMR studies of the base and sequence dependent recognition of the DNA minor groove by netropsin; Patel DJ et al.; We have investigated intermolecular interactions and conformational features of the netropsin complexes with d(G1-G2-A3-A4-T5-T6-C7-C8) duplex (AATT 8-mer) and the d(G1-G2-T3-A4-T5-A6-C7-C8) duplex (TATA 8-mer) by one and two-dimensional NMR studies in solution . We have assigned the amide, pyrrole and methylene protons of netropsin and the base and sugar H1' protons of the nucleic acid from an analysis of the nuclear Overhauser effect (NOESY) and correlated (COSY) spectra of the complex at 25 degrees C . The directionality of the observed distance-dependent NOEs demonstrates that the 8-mer helices remain right-handed and that the arrangement of concave and convex face protons of netropsin are retained in the complexes . The observed changes in NOE patterns and chemical shift changes on complex formation suggest small conformational changes in the nucleic acid at the AATT and TATA antibiotic binding sites and possibly the flanking G.C base pairs . We observe intermolecular NOEs between all three amide and both pyrrole protons on the concave face of the antibiotic and the minor groove adenosine H2 proton of the two central A4.T5 base pairs of the AATT 8-mer and TATA 8-mer duplexes . The concave face pyrrole protons of the antibiotic also exhibit NOEs to the sugar H1' protons of residues 5 and 6 in the AATT and TATA 8-mer complexes . We also detect intermolecular NOEs between the guanidino and propioamidino methylene protons at either end of netropsin and the adenosine H2 proton of the two flanking A3.T6 base pairs in the AATT 8-mer and T3.A6 base pairs in the TATA 8-mer duplexes . These studies establish a set of nine contacts between the concave face of the antibiotic and the minor groove AATT segment and TATA segment of the 8-mer duplexes in solution . The observed magnitude of the NOEs require that there be no intervening water molecules sandwiched between the concave face of the antibiotic and the minor groove of the DNA so that release of the minor groove spine of hydration is a prerequisite for netropsin complex formation . The observed differences in the netropsin amide proton chemical shifts in the AATT 8-mer and TATA 8-mer complexes suggest differences in the strength and/or type of intermolecular hydrogen bonds at the AATT and TATA binding sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Infect Immun, 1985 Jul, 49(1), 84 - 9
Mechanism of polymyxin B-mediated lysis of lipopolysaccharide-treated erythrocytes; Carr C Jr et al.; A novel system was used previously to characterize the dynamic interaction of a polysaccharide-deficient, lipid-rich lipopolysaccharide (LPS) with rabbit erythrocytes (RaRBC) . Exposure of the RaRBC to the LPS rendered them sensitive to induction of hemolysis by the cationic antibiotic polymyxin B (PB) in a time- and temperature-independent manner . Subsequent decay in the response of LPS-sensitized cells to PB was shown to be critically dependent on both the time and temperature of incubation of RaRBC with LPS and to be independent of a change in LPS binding (Carr and Morrison, Infect . Immun . 43:600-606, 1984) . In the present study, we performed experiments designed to define the mechanism by which PB mediates hemolysis of LPS-sensitized RaRBC . Experiments were performed to examine the molecular requirements of the LPS and the PB that were essential for hemolytic activity . The capacity of various cations to mediate hemolysis of LPS-sensitized RaRBC or to block PB-mediated hemolysis and the temperature dependence of the PB lytic reaction were investigated . The results of these experiments suggest that PB-mediated hemolysis of LPS-treated erythrocytes is dependent upon an initial ionic association of PB with erythrocyte membrane-bound LPS, followed by hydrophobic insertion of the PB fatty acid into the erythrocyte membrane lipid bilayer.

J Cell Biol, 1985 Jul, 101(1), 60 - 5
Monensin-resistant mouse Balb/3T3 cell mutant with aberrant penetration of vesicular stomatitis virus; Ono M et al.; A mutant (MO-5) resistant to monensin (an ionophoric antibiotic) derived from the mouse Balb/3T3 cell line, was a poor host for vesicular stomatitis virus (VSV) or semliki forest virus (SFV) multiplication . The yield of VSV particles in MO-5 is one 100-fold reduced as is VSV-dependent RNA synthesis . In contrast to a pH-remedial mutant, the abortive production of infectious VSV particles in MO-5 cells was not restored by low pH treatment . The pH values in the endosome and the lysosome of MO-5 cells were 5.2 and 5.4, respectively, values that were comparable to the pH value in Balb/3T3 cells . Assays with {3H}uridine-labeled VSV indicated similar binding of VSV in MO-5: percoll gradient centrifugation analysis of {35S}methionine-labeled VSV-infected Balb/3T3 showed accumulation of VSV in the lysosome fraction 20 min after VSV infection, whereas VSV can be found mainly in endosome/Golgi fraction of MO-5 cells after 40 to 60 min on the percoll gradients . Degradation of {35S}methionine-labeled VSV was observed at a significant rate in Balb/3T3 cells, but not in MO-5 cells . The monensin-resistant somatic cell may thus provide a genetic route to study the mechanism of endocytosis or transport of enveloped viruses.

Diagn Microbiol Infect Dis, 1985 Jul, 3(4), 283 - 94
Medium-dependent properties of mycoplasmas; Clark HW et al.; Without a cell wall, the morphology, growth rate, and composition of mycoplasmas are culture media-dependent with variable properties best described as environmentally related . The adaptation of mycoplasmas to either a tissue cell or cell-free culture media, with dependency upon specific animal or plant products for survival, has led to investigations of their human host-related properties . The influence of culture media on the antibiotic sensitivities of mycoplasmas was measured by use of three different broths in two different assay systems . The variable results indicate that the inhibition of mycoplasma protein synthesis or growth may also be host-tissue dependent . The addition of noninhibitory penicillins to different culture media was found to affect the composition and antigenicity of some mycoplasmas . Using the complement fixation test, we found some human sera that were more reactive than rabbit antisera to mycoplasmas cultured in human synovial broth or in myelin-enriched broth . Mycoplasmas cultured in human lung broth and pig lung broth had media-dependent antigenicity . The antigenicity and the growth of mycoplasmas were found to depend on the proteolytic enzymes used to provide the essential peptides in tissue broths . The media-affected mycoplasmas indicate the presence of species-, strain-, and tissue-specific antigen sites that may determine immunopathogenicity in the genetically susceptible host.

Biochem Biophys Res Commun, 1985 Jun 28, 129(3), 965 - 71
Bacterial lipopeptides induce ion-conducting pores in planar bilayers; Maget-Dana R et al.; Bacterial lipopeptides, known for their antibiotic activities, have been tested for their ability to interact with lipid membranes . These lipopeptides, Iturin A, Bacillomycin L and D and Peptidolipin NA present analogous structural characteristics: a heptapeptidic cycle is linked to a hydrocarbon chain . We present evidence that these lipopeptides modify the conductance of planar bilayers by forming ion-conducting pores.

J Mol Biol, 1985 Jun 25, 183(4), 553 - 63
Binding of an antitumor drug to DNA, Netropsin and C-G-C-G-A-A-T-T-BrC-G-C-G; Kopka ML et al.; The antitumor antibiotic netropsin has been co-crystallized with a double-helical B-DNA dodecanucleotide of sequence: C-G-C-G-A-A-T-T-BrC-G-C-G, and the structure of the complex has been solved by X-ray diffraction at a resolution of 2.2 A . The structure has been refined independently by Jack-Levitt and Hendrickson-Konnert least-squares methods, leading to a final residual error of 0.257 by the Jack-Levitt approach (0.211 for two-sigma data) or 0.248 by the Hendrickson-Konnert approach, with no significant difference between refined structures . The netropsin molecule displaces the spine of hydration and fits snugly within the minor groove in the A-A-T-T center . It widens the groove slightly and bends the helix axis back by 8 degrees, but neither unwinds nor elongates the double helix . The drug molecule is held in place by amide NH hydrogen bonds that bridge adenine N-3 and thymine O-2 atoms, exactly as with the spine of hydration . The requirement of A X T base-pairs in the binding site arises because the N-2 amino group of guanine would demand impermissibly close contacts with netropsin . It is proposed that substitution of imidazole for pyrrole in netropsin should create a family of "lexitropsins" capable of reading G X C-containing base sequences.

J Comp Neurol, 1985 Jun 22, 236(4), 523 - 37
Freeze-fracture study of filipin binding in photoreceptor outer segments and pigment epithelium of dystrophic and normal retinas; Caldwell RB et al.; We have studied sterol distribution in the retinal pigment epithelial (RPE) microvillous and outer segment disc membranes of rats with inherited retinal degeneration (RCS; RCS-p/+) and of normal genetic controls (RCS-rdy+, RCS-rdy+-p/+) by using the polyene antibiotic filipin, which binds specifically to 3-B-hydroxy-sterols, and freeze-fracture techniques . Retinas were perfusion-fixed, incubated with filipin in the same fixative, and prepared routinely for freeze-fracture electron microscopy . In the normal retina, the distribution of filipin binding sites on both RPE microvillous and outer segment disc membranes changes during development . Prior to outer segment elongation and the onset of phagocytosis (10 days postnatal), filipin sterol complexes are homogeneously distributed in both microvillous and outer segment membranes . With the onset of phagocytosis (2 weeks postnatal and later) filipin binding in both tissues forms a proximal-to-distal gradient, and binding sites decrease as distance from the cell body increases . In the normal RPE microvillous membranes, binding sites are numerous proximally and sparse on the distal tips . In the normal outer segment disc membranes, binding sites are often present on the basal discs, but are sparse on the intact apical discs prior to shedding . As the discs are cast off and engulfed by the RPE, however, filipin binding increases on both disc and phagosome membranes . In the dystrophic retina, the distribution of filipin binding sites differs from the normal . First, in the microvillous membranes, the proximal-to-distal gradient in filipin binding is rarely present at 2 weeks postnatal and becomes prominent only after the buildup of membranous debris has begun (3-5 weeks postnatal) . Second, as the photoreceptors degenerate and the membrane debris disappears (4 months postnatal), filipin binding on the microvillous membranes becomes relatively sparse and homogeneous . Third, filipin binding on the intact disc membranes does not change with outer segment elongation, and numerous filipin binding sites are present on both apical and basal outer segment disc membranes . Fourth, large aggregates of filipin binding sites occupy the vast expanses of particle-free areas of debris membranes which accumulate between the photoreceptors and the RPE . These changes in the amount and distribution of filipin binding sites in the dystrophic retina add to the evidence that the disease process involves outer segment as well as RPE membranes and suggest that alterations in cholesterol distribution could contribute to the phagocytic defect.

Biochemistry, 1985 Jun 18, 24(13), 3214 - 9
DNA damage induced by bleomycin in the presence of dibucaine is not predictive of cell growth inhibition; Berry DE et al.; Growth inhibition and cell killing by bleomycin are believed to be related to the ability of this antibiotic to cleave chromosomal DNA . Because bleomycin has an intracellular site of action, its ability to cross biological membranes must be critical to its overall effectiveness as an antitumor agent . The local anesthetic dibucaine acts to enhance membrane fluidity; therefore, the reported ability of this local anesthetic to modulate bleomycin effects on KB cells was investigated . Cells were treated with various bleomycin congeners in the presence or absence of dibucaine for 24 h . Dibucaine enhanced the inhibition of cell growth mediated by bleomycin A2, demethylbleomycin A2, bleomycin B2, and isobleomycin A2 . N-Acetylbleomycin A2 did not inhibit cell growth in the absence of dibucaine, but it was inhibitory in the presence of dibucaine . Cells treated simultaneously for analysis of DNA breakage on alkaline sucrose gradients revealed that breakage was also enhanced in the presence of dibucaine . The degree of enhancement varied with dose and bleomycin congener . N-Acetylbleomycin A2 did not induce DNA breakage in either the absence or the presence of dibucaine . While growth inhibition and net DNA breakage correlated reasonably well in the absence of dibucaine for each bleomycin analogue tested, proportionality was lost in the presence of dibucaine, and very little DNA breakage was present when growth inhibition was complete . These observations imply that, at least in the presence of dibucaine, bleomycin may mediate growth inhibition at some locus in addition to chromosomal DNA and, also, that a given net amount of bleomycin analogue induced DNA damage per se does not produce a specific degree of growth inhibition.

Biochemistry, 1985 Jun 18, 24(13), 3199 - 207
Interaction of bleomycin A2 with deoxyribonucleic acid: DNA unwinding and inhibition of bleomycin-induced DNA breakage by cationic thiazole amides related to bleomycin A2; Fisher LM et al.; The association of the antitumor antibiotic bleomycin A2 with DNA has been investigated by employing several 2-substituted thiazole-4-carboxamides, structurally related to the cationic terminus of the drug . With a 5'-32P-labeled DNA restriction fragment from plasmid pBR322 as substrate, these compounds have been shown to inhibit bleomycin-induced DNA breakage . Analogues possessing 2'-aromatic substituents on the bithiazole ring were more potent inhibitors than those carrying 2'-aliphatic groups, e.g., the acetyl dipeptide A2 . The degree of inhibition was similar at all scission sites on DNA, and inclusion of the analogues did not induce bleomycin cleavage at new sites . DNA binding of bithiazole derivatives has also been studied by two complementary topological methods . Two-dimensional gel electrophoresis using a population of DNA topoisomers and DNA relaxation experiments involving calf thymus DNA topoisomerase I and pBR322 DNA reveal that bleomycin bithiazole analogues unwind closed circular duplex DNA . The inhibition and unwinding studies together support recent NMR studies suggesting that both bleomycin A2 and synthetic bithiazole derivatives bind to DNA by an intercalative mechanism . The results are discussed in relation to the DNA breakage properties of bleomycin A2.

Carbohydr Res, 1985 Jun 15, 139, 285 - 91
Compartmentation of glycogen metabolism in the liver; Ching R et al.; The incorporation of radioactivity into liver glycogen has been shown not only to be a metabolically inhomogeneous process but also to depend critically on the nature of the precursor . D-Galactose is incorporated into glycogen by a mechanism which is separate from that associated with the incorporation of D-glucose . D-Galactose is favoured for incorporation into high-molecular-weight glycogen and consequently is affected more by treatment of the animal with the antibiotic tunicamycin, since high-molecular-weight glycogen is preferentially found in the lysosomal compartment.

Am J Med, 1985 Jun 7, 78(6A), 73 - 8
Review of adverse experiences and tolerability in the first 2,516 patients treated with imipenem/cilastatin; Calandra GB et al.; The clinical and laboratory data relating to the adverse experiences and tolerability of imipenem/cilastatin in the first 2,516 patients treated with the antibiotic are reviewed, with special reference to the last 793 . Clinical adverse experiences were predominantly related to the gastrointestinal system (nausea and vomiting), local injection site, and allergy (rash) . A low frequency of drug-related seizures was also reported . The most frequent adverse laboratory experiences were transient elevations of liver function test values . In general, the safety profile was similar to that of other beta-lactam antibiotics.

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