Pharmacotherapy, 1989, 9(3), 158 - 64 Prospective surveillance of antibiotic-associated coagulopathy in 970 patients; Grasela TH Jr et al.; N-methyl-thio-tetrazole (NMTT) has been proposed as a causative factor in antibiotic-associated coagulopathy . To evaluate this hypothesis, a nationwide surveillance program was initiated to determine the relative frequency of antibiotic-associated coagulopathy and the importance of specific risk factors . A total of 970 patients were studied, with 491 being treated for infections and 479 receiving antimicrobial surgical prophylaxis . The NMTT-containing antibiotic cefotetan was compared with non-NMTT-containing antibiotics, for example, cefoxitin and cefazolin (prophylaxis only), and an aminoglycoside-antianaerobic (AG + AA) combination . Prothrombin time (PT) and partial thromboplastin time (PTT) were measured for each patient prior to the start of antibiotics and within 24-96 hours after the conclusion of drug administration . The patient population was relatively young {mean (SD) age 51.0 (20) yrs} with good nutritional status . The overall frequency of hypoprothrombinemia (4.5%) and bleeding (1.7%) was very low, and was highest with the use of AG + AA (p less than 0.05) . No statistical differences were observed for the remaining antibiotic regimens in either the prophylaxis or treatment group . Logistic regression analysis identified treatment with the AG + AA combination, presence of liver disease, and renal dysfunction as factors associated with an increased risk of hypoprothrombinemia . In conclusion, this study suggests that the frequency of antibiotic-associated coagulopathy is low, regardless of antibiotic, in patients who are not critically ill and not malnourished. Farmaco, 1989 Jan, 44(1), 89 - 95 Synthesis and antimicrobial activity of some pyrrole derivatives . IV--2-arylidenhydrazino-3-ethoxycarbonyl (or cyano) pyrrole derivatives; Cocco MT et al.; A new series of pyrrole derivatives obtained by heterocyclization of N1-aryliden-3-ethoxycarbonyl (or cyano) acetamidrazones with alpha-bromoketones was described . The in vitro microbiological investigation showed that none of the 2-arylidenhydrazinopyrrole derivatives presented any noteworthy activity. Farmaco, 1989 Jan, 44(1), 51 - 63 {Substances with antibacterial and antifungal activity . VI . Synthesis and microbiologic activity of new derivatives of 1,5-diarylpyrrole and 1,4-pyrrolphenylene}; Porretta GC et al.; New 1,5-diarylpyrrole and 1,4-pyrrolphenylene derivatives were prepared to study influence on the microbiological activity of an unsubstituted pyrrole nucleus or of a double identical molecular structure . Antimicrobial data in comparision with antifungal antibiotic pyrrolnitrin showed that all tested compounds exhibited very poor antifungal and antibacterial activity . Only some derivatives showed a selective activity against strains of Candida sp . and against strains of gram-positive or gram-negative bacteria. Eur Surg Res, 1989, 21 Suppl 1, 1 - 5 Short-term antimicrobial prophylaxis in surgery . The state of the art; Rodolico G et al.; The authors pointed out that contamination may be exogenous, as a result of invasive diagnostic techniques, patient preparation, surgery, catheter insertion and wound dressing, or endogenous, especially in patients with specific risk factors (age, metabolic disorder, malnutrition, immunodeficiency) and aspecific risk factors (anesthesia, blood transfusion, surgery) . Pharmacologic prophylaxis of infection may be unspecific (artificial nutrients, anticoagulants, immunomodulators) or specific (antibiotics) . Prophylaxis is indicated in clean-contaminated and contaminated surgery; antibiotic chemoprophylaxis is also indicated in risk patients and permanent prosthesis surgery . The authors emphasized that antibiotics are no substitution for careful surgery. J Pediatr Gastroenterol Nutr, 1989 Jan, 8(1), 89 - 94 Functional capacity of colostral leukocytes from women delivering prematurely; Schlesinger L et al.; The phagocytic, bactericidal, and metabolic activity of colostral leukocytes from mothers delivering preterm infants was compared with that of colostral leukocytes from mothers of term infants . In addition, the proliferative capacity of colostral lymphocytes was compared . Preterm adherent colostral leukocytes had a significantly higher phagocytic index than term colostral adherent leukocytes . Mean +/- SEM values were 5.4 +/- 0.5 versus 2.7 +/- 0.2, respectively (p less than 0.001) . Bactericidal capacity against Escherichia coli and nitroblue tetrazolium reduction of preterm and term colostral leukocytes were comparable . Lymphocyte proliferative response was equivalent in preterm and term milk . We conclude that colostral leukocytes from preterm mothers are at least as functional in their antimicrobial activity and possibly phagocytose even better than the colostral cells of mothers of term infants. Scand J Infect Dis, 1989, 21(1), 33 - 41 A new diagnostic approach to the patient with severe pneumonia; Sorensen J et al.; 36 patients with severe community-acquired pneumonia, treated in an intensive care unit (ICU), were examined in a prospective study using a comprehensive diagnostic program to establish an early etiological diagnosis . The resulting prompt and adequate antimicrobial therapy may have decreased the number of fatal cases . Special emphasis was placed on the use of a method incorporating fiberoptic bronchoscopy, together with protected brush sampling and bronchial lavage . An etiological diagnosis was established in 81% (29/36) of the cases . This etiological diagnosis was established within 48-72 h in 53% (19/36) of the patients, S . pneumoniae being the most frequent agent found (12 patients) . This information, however, was poorly utilized since in only 11/19 of these patients was the antimicrobial therapy changed from a broad-spectrum antibiotic to a more specific narrow spectrum agent . The overall mortality rate was 22% (8/36) . 7/8 patients who died had compromising factors . Most deaths in community-acquired pneumonia are still associated with pneumococcal infection . We conclude that fiberoptic bronchoscopy with brush samples via a plugged double lumen catheter provides the least misleading information concerning the etiological agent in pneumonia; sampling should be done as soon as possible after admission to the hospital, ideally before the need for ICU treatment; factors other than prompt antimicrobial therapy may influence the outcome of severe community-acquired pneumonia. Padiatr Padol, 1989, 24(1), 49 - 61 {Diagnosis and therapeutic strategies in pneumonia in childhood}; Schmitzberger R et al.; Acute lower respiratory tract infections remain a major cause of morbidity in infants and children . In the majority of patients therapy is complicated by difficulties in securing a specific diagnosis and identification of the causative organism . Treatment is therefore largely based on experiential rather than experimental data . In our study we have tried in 722 patients with pneumonia to correlate the clinical findings with the causative agents . Age and a careful medical history give good clues towards the most probable aetiologic agent . Additional information is gained by the course of the illness . Physical examination, chest X-ray and few limited laboratory tests can also be of help to identify the most likely organism . Once the organism is identified, appropriate antimicrobial agent can be started . It is not only the choice of the antimicrobial substance, but also the choice of the proper total daily dose, dosage interval and mode of administration . By this management we had good results also in elimination of problem organism such as pseudomonas in CF. Padiatr Padol, 1989, 24(1), 33 - 42 {Empirical antimicrobial therapy of infection and fever episodes in children and adolescents with neutropenia caused by cytotoxic chemotherapy}; Fink FM et al.; The experience with empirical antimicrobial therapy of septicemia and febrile episodes in pediatric neutropenic patients was analyzed retrospectively . Between January 1985 and March 1988 in 49 patients 77 episodes were observed . Bacteremia was found in 15 (20%), culture proven localized bacterial infection in 11 (14%) and clinically diagnosed bacterial infection was found in 7 (9%) of the febrile episodes . Thus, 33 (43%) documented bacterial infections were observed . For initial therapy a combination of aminoglycoside plus 2nd/3rd generation cephalosporin (60%) or aminoglycoside plus piperacillin (30%) was usually chosen . Both regimens were equally effective . 52% and 56%, respectively, were sufficiently treated with the initial regimen . 95% of all episodes resolved completely, the mortality rate was 5% . Central venous catheters remained in situ in 84% of the cases . The period of time necessary for recovery of granulopoiesis had an influence on the therapy success. J Foot Surg, 1989 Jan-Feb, 28(1), 54 - 9 Antibiotic-impregnated bone cement: an in vitro comparative analysis; Heard GS et al.; This manuscript examines the in vitro antibacterial activity of eight different antibiotics when mixed with polymethyl methacrylate . Two different parameters are presented as being important considerations in the choice of antibiotic . One parameter is the bacterial inhibition created by the direct contact of the antibiotic-impregnated bone cement . The second parameter is the bacterial inhibition produced by diffusion of antibiotic from the bone cement into the surrounding liquid medium . These two experimental models were created to establish the contiguous and remote antimicrobial effects of antibiotic-impregnated bone cement. Acta Microbiol Hung, 1989, 36(4), 425 - 32 Antimicrobial and immunomodulating effects of some phenolic glycosides; Molnar J et al.; Several phenolic glycosides, i.e . acteoside, desrhamnosyl acteoside, and purpureaside A, B and C, exerted weak antibacterial effects on Escherichia coli . Acteoside had antiplasmid effects, including F'lac plasmid elimination, and inhibited kanamycin resistance transfer in E . coli . Acteoside, desrhamnosyl acteoside and purpureaside A displayed antiviral effect on Aujeszky virus . All of the phenolic glycosides decreased some human leucocyte functions, including rosette formation, mitogen-induced blast transformation and phagocytic activity in vitro . The purpureaside C had significant proinflammatory action, however, other phenolic glycosides showed neither proinflammatory nor antiinflammatory effect on carrageenin-induced inflammation in vivo. J Clin Dent, 1989 Spring, 1(4), 96 - 101 Antimicrobial action of sanguinarine; Godowski KC; Sanguinarine is a benzophenanthridine alkaloid derived from rhizomes of Sanguinaria canadensis L . (bloodroot) . It is a cationic molecule which converts from an iminium ion form at pH less than 6 to an alkanolamine form at pH greater than 7 . Sanguinaria extract is composed of sanguinarine and five other closely related alkaloids . The safety profile of both sanguinarine and sanguinaria extract provide a broad margin for their safe use in oral health products . Sanguinarine has broad antimicrobial activity as well as antiinflammatory properties . In vitro studies indicate that the anti-plaque action of sanguinaria is due to its ability to inhibit bacterial adherence to newly formed pellicle, its retention in plaque being 10-100 times its saliva concentration, and due to its antimicrobic properties . The MIC of sanguinarine ranges from 1 to 32 micrograms/mL for most species of plaque bacteria . Long term use of sanguinaria-containing toothpaste and oral rinse products does not predispose users to detrimental shifts in oral flora . Electron microscopic studies of bacteria exposed to sanguinarine demonstrate that bacteria aggregate and become morphologically irregular . Sanguinarine-containing slow release polymer systems are currently being developed for use in periodontitis treatment applications. Drug Metabol Drug Interact, 1989, 7(1), 29 - 51 Interaction of amine oxides and quaternary ammonium salts with membrane and membrane-associated processes in E . coli cells: mode of action; Kopecka-Leitmanova A et al.; The antimicrobials (1-methyldodecyl)dimethylamine oxide and (1-methyldodecyl)trimethylammonium bromide affect the cytoplasmic membrane of E . coli . The interaction results in release of intracellular material (K+, 260nm-absorbing material), an effect on dehydrogenase enzyme activity and inhibition of respiration . The final effect of both substances is the same; they differ only in their dynamics . The effect of the membrane was correlated with parameters characterizing these surfactants i.e . critical micelle concentration (c.m.c.) minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) over the concentration range of 10(-4) to 10(-1) mmol/dm3 of active substance . The three stage mode of action model can be summarized as follows: 1-polar (coulombic) interactions, 2-polar and hydrophobic interactions, 3-hydrophobic interactions (extraction and solubilization) . The polar and hydrophobic interactions (1st and 2nd stage) are discussed also in relation to model membranes. Postepy Hig Med Dosw, 1989, 43(1), 119 - 60 {New trends in studies of the pharmacologic activity of microbial metabolites}; Chmiel A; A new broad concept and novel approaches in the search for bioactive microbial metabolites are discussed . Methodology of the screening systems and assay techniques for the pharmacological and immunopharmacological activity of these products is presented . The value of the preliminary target-selective screening procedures is illustrated with a number of the pharmacologically active microbial products, among which the enzyme inhibitors are extremely important . Products with immunopharmacological activity are developed for organ transplantation and antitumor therapy . Another question discussed in the paper is non-antimicrobial and non-antitumor applications of the antibiotics. ZWR, 1989 Jan, 98(1), 30 - 6 {Antibiotic therapy for odontogenic induced orofacial infections under office conditions}; Knoll-Kohler E; Due to the dominance of anaerobics in dentogen-induced orofacial inflammations the possibility of their treatment is restricted to a few groups of substances of different chemical structure (penicillins, lincosamides, nitroimidazoles, tetracyclins and macrolide antibiotics) for ambulant patients . The order of application for these different substances is determined by the local diagnosis and the pathophysiological state of the patient . The general anamnesis of disease, drugs and allergy as well as the knowledge of pharmacodynamics and pharmacokinetics of the substances to be applied are, therefore, indispensible for an optimal antimicrobial therapy. Arch Androl, 1989, 23(3), 243 - 8 Chlamydial infection and male infertility: an epidemiological study; Custo GM et al.; Chlamydia-positive genitourinary infections are common causes of male and female infertility . Semen abnormalities are often associated with Chlamydia infections . A large population of male patients, admitted to our clinic for genitourinary infection, were examined for genitourinary pathogens, including Chlamydia, and for semen abnormalities . There were higher abnormalities semen in Chlamydia-infected patients than either non-Chlamydia-infected or healthy controls . Chlamydia therapy by antimicrobial agents improved semen characteristics . Chlamydia infection contributes to seminal fluid abnormalities and probably to male infertility . A search for chlamydial infection is warranted whenever semen abnormalities are noted . An antimicrobial therapy improves semen quality when effective in eradicating Chlamydia. Ann Ital Chir, 1989, 60(3), 183 - 6; discussion 187 {Short-term antibiotic prophylaxis with ceftriaxone in general surgery}; La Rosa M et al.; The authors report their own experience on the efficacy of a short term antimicrobial prophylaxis involving a long-acting cephalosporin, ceftriaxone (Rocefin), in surgical patients . A study was carried out to evaluate the efficacy of a single dose of 1 or 2 g by i.v . administered 1 h . before elective surgery . 100 patients were admitted to study . Therapeutic success was achieved in 92 cases (92%). Scand J Gastroenterol Suppl, 1989, 169, 70 - 80 Adverse reactions to furazolidone and other drugs . A comparative review; Altamirano A et al.; Furazolidone is a synthetic nitrofuran with a broad spectrum of antimicrobial action and has been widely used in the treatment of gastrointestinal infections . This article reviews the adverse reactions to furazolidone reported in the world literature . Of 10,443 adults and children who were treated with the drug, approximately 8.3% (864) experienced such reactions . Because some of these patients had more than 1 adverse reaction, 1178 reactions were reported in these studies . Nausea with vomiting, the commonest adverse reaction, was reported by 51% of the 864 patients who experienced adverse reactions . The authors compare the adverse reactions to furazolidone with those reported for other antimicrobial and antiprotozoal drugs that are frequently used to treat gastrointestinal infections. Scand J Gastroenterol Suppl, 1989, 169, 24 - 7 Acute invasive diarrhea in the pediatric patient; Guerrero R; In acute invasive diarrhea, the pathogen penetrates the epithelial cells of the intestinal mucosa . Symptoms are produced by one or more of the following mechanisms: production of enterotoxins, increased synthesis of prostaglandins, and impaired reabsorption of fluids and electrolytes . The invasive process often results in dysentery, which is characterized by watery stools containing blood and mucus, accompanied by cramps, rectal burning, fever, and, sometimes, toxicity . Among the complications are bacteremia and toxic megacolon . Diagnosis is based on the patient's clinical condition and examination of stools . Microscopic examination of stools can rule out parasites and detect leukocytes, particularly polymorphonuclear leukocytes, a finding that suggests a bacterial origin for the disease . Because most patients are not severely dehydrated, rehydration is not the mainstay of treatment; in most cases, fluids can be replaced orally . Absorbents are ineffective, and antiperistaltic drugs should not be used routinely in children . Although often unnecessary in simple cases of invasive diarrhea, antimicrobials are useful when risk factors related to age, clinical condition, malnourishment, dehydration, or underlying disease are present . In such cases, antimicrobial therapy should begin when the clinical diagnosis has been made, to ensure the best clinical response. J R Soc Med, 1989, 82 Suppl 17, 44 - 50; discussion 50-1 Treatment of severe malaria; Warrell DA; In the treatment of severe Plasmodium falciparum infection antimalarial drugs should, ideally, be given by controlled rate intravenous infusion until the patient is able to swallow tablets . In cases where infection has been acquired in a chloroquine resistant area, and where it has broken through chloroquine prophylaxis or where the geographical origin or species are uncertain, quinine is the treatment of choice . When access to parenteral quinine is likely to be delayed, parenteral quinidine is an effective alternative . A loading dose of quinine is recommended in order to achieve therapeutic plasma concentrations as quickly as possible . In the case of chloroquine sensitive P . falciparum infection, chloroquine, which can be given safely by slow intravenous infusion, may be more rapidly effective and has fewer toxic effects than quinine . There is limited experience with parenteral administration of pyrimethamine sulphonamide combinations such as Fansidar, and resistance to these drugs has developed in South East Asia and elsewhere . Mefloquine and halofantrine cannot be given parenterally . Qinghaosu derivatives are not readily available and have not been adequately tested outside China . Supportive treatment includes the prevention or early detection and treatment of complications, strict attention to fluid balance, provision of adequate nursing for unconscious patients and avoidance of harmful ancillary treatments . Anaemia is inevitable and out of proportion to detectable parasitaemia . Hypotension and shock ('algid malaria') are often attributable to secondary gram-negative septicaemia requiring appropriate antimicrobial therapy and haemodynamic resuscitation . Many patients with severe falciparum malaria are hypovolaemic on admission to hospital and require cautious fluid replacement . Failure to rehydrate these patients may lead to circulatory collapse, lactic acidosis, renal failure and severe hyponatraemia.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Cancer Clin Oncol, 1989, 25 Suppl 2, S9 - 16 Evaluation of fever in the patient with cancer; Pizzo PA; During the last decade, the survival of patients with fever and neutropenia has continued to improve . This is largely a reflection of the increasing repertoire of antimicrobial agents available to treat the fevers and infections that arise in this ever-increasing population of patients . Although it would be optimal if therapeutic decisions could always be made based on the microbial isolates and their sensitivity patterns, this is generally not possible in the cancer patient . Fever remains the predominant manifestation of infection, but the underlying microbial etiology is infrequently delineated . In spite of improved diagnostic tests, clinical acumen along with vigilant and repetitive patient assessment remain the cornerstone for evaluation of the cancer patient who becomes febrile . Indeed, strict adherence to simple principles can have a significant impact on improving the chances for survival of cancer patients who develop fever or infection. Eur J Cancer Clin Oncol, 1989, 25 Suppl 2, S43 - 51 Empirical antibiotics for febrile neutropenic cancer patients; Hathorn JW; The empirical institution of broad spectrum antibiotics for febrile neutropenic cancer patients has become standard medical practice . Traditionally, the antibiotics consisted of a combination of agents selected to maximize activity against the most commonly isolated pathogens, and often employed agents with synergistic antimicrobial activity . Recent additions to the antibiotic armamentarium, however, have provided single agents with equivalent spectra of activity, thus potentially allowing a 'monotherapeutic' alternative to the combination regimens . The empirical utilization of antibiotics for the febrile, neutropenic episode is reviewed, with emphasis on recent clinical studies evaluating select monotherapeutic 'agents'. Clin Pharmacokinet, 1989, 17 Suppl 1, 29 - 67 Clinical pharmacokinetics in infants and children . A reappraisal; Kearns GL et al.; A significant increase in the knowledge base in paediatric clinical pharmacology has occurred over the past 2 decades and has largely been the result of important scientific and sociological advancements pertaining to paediatric therapeutics . Although the data on drug disposition in infants and children have increased considerably over the past few years, pharmacokinetic-pharmacodynamic interactions, particularly the effect of development on pharmacodynamics, remain poorly understood . The impact of developmental physiology on drug absorption, distribution, metabolism and elimination in infants and children is reviewed and contrasted to the determinants of clinical pharmacokinetics in neonates . The most notable differences in drug disposition between infants and children when compared with neonates and young adults centre around alterations in body water and serum protein composition and the affinity/capacity for hepatic biotransformation of xenobiotics . As opposed to examining the effect of age on the disposition of specific compounds, the differences in developmental pharmacology are highlighted by the review of important and/or emerging pharmacokinetic-pharmacodynamic controversies in infants and children . These include the issues of altered drug distribution and metabolism in cystic fibrosis, pharmacokinetic determinants of successful antimicrobial therapy in bacterial meningitis and the pharmacokinetic determinants of immunosuppression treatment with cyclosporin . The pharmacological differences which are characteristic of development in both infants and children are also reviewed by examination of considerations for clinical pharmacokinetic evaluations such as specific routes and techniques for both drug administration and determination of sampling strategies . Clinical pharmacokinetics will continue to function as a bridge between the generation of new information and the practical application of this knowledge . Consequently, pharmacokinetics provides a pharmacological tool for use in research and clinical care . The clinical application of this tool is examined by a review of the pertinent assumptions and limitations, as well as useful mathematical techniques for use in paediatric patients . Additionally, 'non-traditional' uses of clinical pharmacokinetics (forensic application and use to evaluate organ function) in infants and children are discussed as are considerations for research use of clinical pharmacokinetic data. Clin Pharmacokinet, 1989, 17 Suppl 1, 105 - 15 Antimicrobial therapy in neonates, infants and children; Brown RD et al.; Many antimicrobial medications may be administered to paediatric patients with a degree of impunity because they are relatively non-toxic and have a wide therapeutic margin . However, because of different pharmacokinetics from those in adults, the potential for toxicity exists with the use of some of these agents . Drug absorption in paediatric patients, either orally or parenterally, is generally similar to that in adults, except among neonates and, particularly, premature neonates . Similarly, in neonates, drug distribution is altered, plasma protein binding is decreased and hepatic metabolism and renal excretory capacity are limited by physiological immaturity . Thus, in neonates, only drugs that have pharmacokinetically derived dosage schedules should be used, and therapeutic monitoring of plasma drug concentrations is recommended during therapy with aminoglycosides, vancomycin and chloramphenicol . In older infants and children, the pharmacokinetics of antimicrobial drugs generally approximate those in adults, and recommended dosages have been determined relative to bodyweight . Therapeutic monitoring of plasma drug concentrations may be important in certain patients, such as those with major organ failure, and may be useful in cases of suspected noncompliance . Additional pharmacokinetic considerations concerning antimicrobial medication and paediatric patients are the extent to which drug therapy penetrates the cerebrospinal fluid in meningitis, and the potential for and implications of exposure of infants to antimicrobial medications excreted in breast milk. Microbios, 1989, 60(242), 23 - 33 Antimicrobial activity of some 2-aminopyrimidines; Ghannoum M et al.; The minimum inhibitory concentration values for a group of pyrimidine derivatives were determined for Gram-positive and Gram-negative bacteria and yeast . The active compounds were further screened . The effect of these compounds on growth and morphology was tested, and their structural antimicrobial activity is discussed. Chem Biol Interact, 1989, 71(2-3), 105 - 46 Structure-activity relationships among mycotoxins; Betina V; Relationships between structural features and biological effects of mycotoxins are reviewed . Structure-activity relationships are characterized at the molecular, subcellular, cellular, or supracellular level . Major chemical and physicochemical factors responsible for bioactivity of mycotoxins are stressed . A variety of chemical families of mycotoxins are then discussed from the point of view of structure-activity relationships . The structurally related families comprise small lactones, macrocyclic lactones, isocoumarin derivatives, aflatoxins and related compounds trichothecenes, anthraquinones, indole-derived tremorgens and selected amino acid-derived mycotoxins such as sporidesmins and cyclosporines . Biological effects of mycotoxins include acute and chronic toxicity, antimicrobial activity, mutagenicity and genotoxicity, carcinogenicity and biochemical modes of action. Neurosurg Rev, 1989, 12(4), 333 - 40 Nocardial cerebral abscess cured with imipenem/amikacin and enucleation; Krone A et al.; A 72 year old female with cerebral abscess due to Nocardia farcinica is reported . Needle aspiration, antimicrobial therapy using a new combination of imipenem and amikacin, and, finally, surgical excision led to prompt and complete recovery . This is the oldest patient to survive cerebral nocardiosis reported in the literature . This infection, is usually regarded as opportunistic and is encountered with increasing frequency in immunocompromised conditions (organ transplantation, chemotherapy, underlying disabling disorder, acquired immunodeficiency syndrome, etc.) . The literature is extensively reviewed for various aspects of this disease including prognostic factors, recent developments in antibiotic therapy (imipenem, amikacin, minocycline etc.) and the essential role of surgery in the treatment strategy. Rev Med Chir Soc Med Nat Iasi, 1989 Jan-Mar, 93(1), 175 - 7 {Pyridazinilides (XIV) . The action of p-phenyl-phenacyl bromide on 3-phenyl-pyridazine}; Caprosu M et al.; This time the synthesis of some new derivatives obtained by the quaternary substitution of one of the heterocyclic nitrogen atoms and by reactions of dipolar cycloaddition is presented . The results of the tests on their antimicrobial and antiinflammatory actions are discussed. Respiration, 1989, 55 Suppl 1, 9 - 13 Role of leukocytes in lung defenses; Coonrod JD; Alveolar macrophages are the primary cells that protect the lung against inhaled or aspirated microbes . They kill microorganisms intracellularly by both oxidative and non-oxidative mechanisms . Alveolar macrophages secrete antimicrobial factors, including lysozyme, peptides, and transferrin, which are found in the bronchoalveolar lining fluid and may kill microbes extracellularly . Macrophage secretory products help initiate a controlled inflammatory response and a limited influx of granulocytes, which appears to be important for complete elimination of many bacterial pathogens from the lung. Respiration, 1989, 55 Suppl 1, 60 - 7 Role of surfactant in alveolar defence against inhaled particles; Curti PC et al.; Alveolar surfactant molecules may concentrate on particulated matter (powders or microbes) with the formation of liposomes . In vitro the spraying of powders on a surfactant film causes the appearance of liposomes and consequent alterations in the tension/area diagram . In animals soon after inhalation of powders fine enough to be deposited in alveoli surfactant liposomes containing powder particles are observed in the alveolar spaces and later on along the airways . The powder content of liposomes collected through a T cannula in the trachea may be demonstrated by chemical or electronic microscopical analysis . Prolonged inhalation of powder may induce surfactant depletion and alveolar bronchiolar instability . In mice exposed for 5 months to silica dust a correlation has been found between surfactant depletion and silica retention in the lung with recruitment of phagocytic cells and increased serum and BAL-lysosomal enzyme activity . In animals treated with ambroxol, the clearance of silica is faster and longer lasting, and the pulmonary alterations are delayed and reduced . The first results of clinical trials with ambroxol in miners seem favorable . Microbes may also be incorporated as powder particles in alveolar surfactant liposomes . Using motile strains, bacteria struggling within a liposome may be observed with a telecamera . Preliminary observations suggest a direct antimicrobial action of ambroxol. Hautarzt, 1989, 40 Suppl 9, 51 - 3 {Urea and urea combinations in ichthyoses}; Schnyder UW; The author recommends differentiated topical treatment of ichthyoses . At present, urea is the base curative for the five main types of this heterogenous group of diseases . Urea is not only effective as a keratolytic agent, but also in its ability to bind water . Whether the inhibition of proliferation, enhancement of penetration and the antimicrobial effects observed with urea are therapeutically important remains to be investigated . The combination of urea and tretinoin displays a beneficial effect on the clinical symptoms of nonerythematosus types of ichthyoses . The more severe the keratinization disorder, the sooner additional systemic treatment with retinoids is indicated. Hautarzt, 1989, 40 Suppl 9, 23 - 6 {Biochemistry, pharmacology and toxicology of urea}; Raab W; In modern dermatology urea has two areas of application: --Applied topically urea is a pharmacologically active substance . It is moisturizing, keratolytic (in high concentrations only), desquamating, antipruritic, and antimicrobial . --Urea supplements and increases the effectivity of glucocorticoids, anthralin (dithranol) and tretinion . Urea-glucocorticoid combinations deserve special attention. Infection, 1989, 17 Suppl 1, S14 - 8 {Enoxacin--comparative pharmacokinetics and tissue penetration}; Sorgel F et al.; The choice of an antimicrobial agent is primarily dependent on its antimicrobial activity and the pharmacokinetics in the host . The gyrase inhibitors differ in their antimicrobial spectrum as well as in their pharmacokinetics . In this review we compare key pharmacokinetic parameters of the most important 4-quinolones . Clearly, there are differences in their absorption, their sensitivity of the absorption process to food or di-or trivalent cations . On a weight basis enoxacin tends to have higher plasma levels then e.g . ciprofloxacin or norfloxacin and also tissue penetration of enoxacin as determined in the Body Fluid Model is superior to ciprofloxacin or norfloxacin . The elimination of enoxacin is mostly by the kidney (approximately 50-60% of dose) another 12-15% are metabolized in the liver . Renal failure therefore requires dose adjustments . The inhibitory effect of enoxacin on other compounds' metabolism has to be considered. Annu Rev Microbiol, 1989, 43, 601 - 27 The evolution of fluorinated quinolones: pharmacology, microbiological activity, clinical uses, and toxicities; Siporin C; The fluorinated quinolones expand the spectrum of antimicrobial activity of the first-generation agents and offer more favorable pharmacokinetic and safety profiles than the older agents . Additionally, the need for only one daily administration of the third-generation quinolones may improve patient compliance . Data from clinical trials suggest that the oral fluoroquinolones provide cost-effective, outpatient therapy for infections previously treated in hospitals with parenteral antimicrobial agents (16) . The third-generation agents do not interfere with metabolism of theophylline, thus making fluoroquinolone treatment of patients receiving theophylline potentially more safe . Given the current focus on cost-containment strategies in health care, the fluorinated quinolones have become an attractive choice for therapy against a variety of bacterial infections . The future for antimicrobials and specifically quinolones looks especially bright with third-generation agents like lomefloxacin under development. Yonsei Med J, 1989, 30(2), 111 - 7 Application of serologic diagnosis of tsutsugamushi disease (scrub typhus) in Korea where the disease was recently recognized to be endemic; Chong Y; In Korea, tsutsugamushi disease is a recently recognized infection . It has become clear that it is more prevalent than leptospirosis or hemorrhagic fever with renal syndrome . Accurate diagnosis of the disease is necessary for the selection of effective antimicrobial agents which can prevent fatalities and shorten the course . For the diagnosis, various serologic tests are used . Sensitivity and specificity of a test depend on various factors . In this report, microbiological aspects of the infection were briefly described and the Weil-Felix, indirect immunofluorescence and indirect immunoperoxidase tests were compared for their applicability in routine use and usefulness in the diagnosis . Their interpretations were also briefly discussed. Pediatrie, 1989, 44(1), 27 - 9 {Cephalhematoma infection in neonatal septicemia}; Meignier M et al.; Most cephalhematomas resorb spontaneously; intervention by means of needle aspiration may introduce infection . In our case, a neonatal septicemia was associated with a large parietal cephalhematoma . The newborn was discharged after treatment of sepsis . Three days later, the diagnosis of infected cephalhematoma was apparent, associated with meningitis and septicemia . The authors discuss the physiopathology of the infection, antimicrobial therapy and careful aspiration when a serious infection is associated with cephalhematoma. Chemotherapy, 1989, 35(5), 389 - 92 Treatment of various infections in an outpatient practice by intramuscular ceftriaxone: home parenteral therapy; Karachalios GN et al.; Ceftriaxone, a broad-spectrum third-generation cephalosporin with a long half-life, was administered intramuscularly to 23 outpatients who had a variety of infectious diseases . Cure was achieved in 21 of the patients (91%) . The results of this study indicate that ceftriaxone is an effective and well-tolerated antimicrobial agent when administered intramuscularly to outpatients with various infections. Adverse Drug React Acute Poisoning Rev, 1989 Summer, 8(2), 73 - 88 Nephrotoxicity of aminoglycosides and cephalosporins in combination; Rankin GO et al.; Early clinical studies with combined cephaloridine and aminoglycoside therapy suggested that a synergistic nephrotoxic interaction was possible between agents in these two classes of antimicrobial drugs . The most compelling evidence supports a synergistic interaction between cephalothin and gentamicin or tobramycin . The documentation for interactions between other cephalosporin-aminoglycoside combinations is not as substantial as with cephalothin, but numerous case reports and clinical studies suggest the possibility of an enhanced nephrotoxic interaction with such regimens . Numerous factors may increase the likelihood of an apparent synergistic nephrotoxic aminoglycoside-cephalosporin interaction . In many cases where potentiation of drug-induced nephrotoxicity has been reported, patients were critically ill, and the underlying pathophysiological condition might have contributed to the resultant renal dysfunction . In addition, nephrotoxicity has been observed more frequently when very large doses of the cephalosporin were used in the combination therapy . Patients receiving cephalosporin-aminoglycoside therapy are also often being given other drugs that have the ability to damage the kidney (e.g . anticancer agents) or drugs that are known to enhance the nephrotoxic potential of the antimicrobial drugs (e.g . loop diuretics) . Therefore, attention must be given to numerous factors in order to minimize the possibility of renal dysfunction developing with combination therapy . The question as to which drug is potentiating the nephrotoxic potential of the other remains to be answered . Although some investigators have suggested that the cephalosporin potentiates the effects of the aminoglycoside, others feel that the reverse is true . Data from the rabbit tend to support aminoglycoside potentiation of cephalosporin-induced nephrotoxicity . Resolution of this problem may, however, have to await the development of a more suitable animal model of the interaction . In addition, a better understanding of the pharmacokinetic interactions between cephalosporins and aminoglycosides and a more precise description of the mechanisms of nephrotoxicity induced by these agents could help uncover the answers to many of these questions . The development of newer antimicrobial drugs with broader microbial coverage and a lesser nephrotoxic potential than agents currently in use may reduce the need for combining cephalosporins and aminoglycoside or provide safer drug combinations for many clinical situations.(ABSTRACT TRUNCATED AT 400 WORDS) Pharmatherapeutica, 1989, 5(5), 312 - 9 Amoxycillin/clavulanic acid ('Augmentin') compared with a combination of aminopenicillin, aminoglycoside and metronidazole in the treatment of pelvic inflammatory disease; Cirau-Vigneron N et al.; A randomized, multi-centre trial was carried out in 152 hospitalized women with pelvic inflammatory disease to evaluate the efficacy and tolerability of amoxycillin/clavulanic acid compared with that of a standard regimen using three antimicrobial agents (aminopenicillin, an aminoglycoside and metronidazole) . Seventy patients initially received 3 to 4 intravenous doses per day of 1 g amoxycillin/200 mg clavulanic acid (mean 7.7 days) and then 4 to 6 tablets per day of 500 mg amoxycillin/125 mg clavulanic acid (mean 11.2 days) . The other group of 82 patients initially received parenteral therapy daily (mean 7.7 days) with a combination of 3 to 4 g amoxycillin or ampicillin, 160 mg gentamicin (or 150 mg dibekacin or tobramycin) and 1.5 g metronidazole, and then oral therapy with 2 to 3 g amoxycillin or ampicillin and 1 to 1.5 g metronidazole daily (11.1 days) . Clinical results, assessed at discharge from hospital (mean 10 days in both groups), were comparable in both groups, with 96% complete or partial response and no failures in the amoxycillin/clavulanic acid group, and 90% complete or partial successes and 5 failures with the triple therapy regimen . Both treatments were well tolerated and very few side-effects were reported. J Oral Pathol Med, 1989 Jan, 18(1), 21 - 7 Recurrent aphthous stomatitis: current concepts of etiology, pathogenesis and management; Scully C et al.; Recurrent aphthous stomatitis (RAS) is a common oral disorder, however, despite detailed clinical, immunologic, hematologic and microbiologic investigation, the etiology of RAS remains unknown . At present, topical steroids and antimicrobial mouth rinses are the mainstays of treatment, but there is still no means of preventing recurrence of the oral ulceration. Blood Purif, 1989, 7(2-3), 115 - 25 Antimicrobial therapy for CAPD-associated peritonitis; Winton MD et al.; Infectious peritonitis continues to be the leading cause of morbidity in patients on continuous ambulatory peritoneal dialysis (CAPD) . Optimum management of CAPD-associated peritonitis requires a concerted effort toward the establishment of the specific agent causing the episode . We have reviewed the current literature relating to the diagnosis and institution of antimicrobial therapy . Controlled comparative trials are needed to determine the efficacy of potentially less toxic therapeutic regimens for peritonitis, for definition of and treatment of exit-site infections, and timing of catheter replacement. Eur Surg Res, 1989, 21 Suppl 1, 6 - 13 Use of a long-acting cephalosporin (ceftriaxone) for antimicrobial prophylaxis in abdominal and biliary surgery; Hell K; Present data available on ceftriaxone (Rocephin) dealing with microbiology, pharmacokinetics (long half-life, tissue penetration ability, tissue concentration present during vulnerable period, etc.), results of clinical trials, and world-wide experience seem to be in favor of ceftriaxone as the antimicrobial of choice for single-dose antibiotic prophylaxis in abdominal and biliary surgery . Single-dose surgical prophylaxis is cost-effective, has a low rate of adverse drug events, and so far does not increase danger of resistance. Eur Surg Res, 1989, 21 Suppl 1, 25 - 32 Ceftriaxone as short-term antimicrobial chemoprophylaxis in orthopedic surgery: a 1-year multicenter follow-up . Preliminary results of a controlled multicentre study; Periti P et al.; In this multicentre study, 883 evaluable patients undergoing orthopedic surgery were randomly assigned to receive antiinfective prophylaxis with either ceftriaxone (Rocephin) or cefamandole . 25 patients in the ceftriaxone group and 29 patients in the cefamandole group (5.6 vs 6.5%) presented with infectious complications within the first 60 days after surgery . Delayed deep wound infections developed in only 1 of 435 patients in the ceftriaxone group compared with 4 of 413 patients in the cefamandole group . Both drugs were well tolerated . The infection rate was twice as high after surgery in conventional operating theatres than after treatment in hypersterile operating theatres (3.3 vs 6.5%); this difference is not statistically significant. Chemotherapy, 1989, 35 Suppl 1, 81 - 8 Comparative study of aztreonam in gram-negative pneumonia versus a therapeutic regimen that includes an aminoglycoside . Spanish Study Group; Marco V et al.; Gram-negative pneumonia is a frequent complication in hospitalized patients, particularly in those with diminished defenses . The severity of the infections makes it necessary to start immediately an empirical antimicrobial therapy that usually combines a broad-spectrum beta-lactam antibiotic with an aminoglycoside (AMG), despite the potential toxicity of this regimen . We have compared the efficacy of a new beta-lactam antibiotic, aztreonam, which shows both a specific spectrum of activity against gram-negative bacteria and a very good diffusion into pulmonary tissue, with that of another antibiotic regimen including an AMG . Of a total of 69 patients, 43 were treated with aztreonam and the remaining patients with an AMG . Both groups were comparable with respect to the severity of infection and underlying pathology . Clinical efficacy was similar in the two regimens (81% aztreonam, 62% AMG) . However, antimicrobial efficacy was superior in the aztreonam group (88% aztreonam, 65% AMG), although differences disappeared in patients treated with the combination amikacin + cefotaxime or ticarcillin in the AMG group . Colonization/superinfection was also similar in both groups, although the selection of gram-negative bacteria occurred more frequently in the AMG group . Our results suggest that aztreonam, in monotherapy, may be a useful alternative for the treatment of gram-negative pneumonia. Hinyokika Kiyo, 1989 Jan, 35(1), 159 - 65 {Clinical efficacy of ceftriaxone administered once daily against pyelonephritis}; Suzuki K et al.; Ceftriaxone (CTRX) was evaluated for clinical efficacy on uncomplicated and complicated pyelonephritis by administering 2 g once daily for 5 days to 16 female patients between 20 and 65 years old (average: 39.7 years); i.e., 3 with uncomplicated pyelonephritis and 13 with complicated pyelonephritis . The pathogens in all 3 cases of uncomplicated pyelonephritis were E . coli . All of them disappeared after the treatment . Twenty-two strains of 10 strains of bacteria were isolated from the 13 cases of complicated pyelonephritis . Twenty of the 22 (91%) strains disappeared . The clinical efficacy was evaluated according to the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on UTI Japan in 15 cases except for 1 case of the complicated type where the CTRX administration was discontinued after the initial dose due to an adverse event . The efficacy rate was 100% in the 3 uncomplicated cases; 'excellent' in 1 case and 'good' in 2, and 92% in 12 of the complicated cases; 'excellent' in 9, 'good' in 2 and 'poor' in 1 (infection was with multiple pathogens including P . aeruginosa) . No abnormal values were observed in any cases except for a slight increase in glutamic-pyruvic transaminase and alkaline phosphatase in one case and skin rash in another case which appeared following the initial dose and required the immediate withdrawal of the drug . CTRX is characterized by a long half-life and shows a strong antibacterial activity against GNRs, especially E . coli . The efficacy rate was high particularly following the initial dose in the acute stage of pyelonephritis.(ABSTRACT TRUNCATED AT 250 WORDS) Diagn Microbiol Infect Dis, 1989 Jan-Feb, 12(1), 93 - 9 Cefotaxime and desacetylcefotaxime in neonates and children: a review of microbiologic, pharmacokinetic, and clinical experience; Jacobs RF et al.; Over the past 5 yr, we have conducted two clinical and two pharmacokinetic investigations of cefotaxime (CTX) and desacetylcefotaxime (dCTX) in neonates, infants, and children . A total of 50 children with culture-proven bacterial meningitis were randomized to receive either 200 mg/kg/day of CTX (n = 23, mean age 24.4 mo) or standard doses of ampicillin (AMP) and chloramphenicol succinate (CAPS; n = 27, mean age 16.6 mo) . Results were similar between the CTX and Amp/CAPS groups for clinical/microbiological cures (100% versus 96%, respectively) and for survival without sequelae (78% vs . 77%, respectively) . All bacterial isolates were sensitive to CTX, and the comparison of the MIC/MBC values for CTX to the CSF bactericidal titers suggested antimicrobial activity for dCTX . In a second clinical trial, 20 infants (1 wk-3 mo) were treated with 200 mg/kg/day of CTX for Gram-negative enteric bacillary meningitis . Cultures of CSF obtained 24 hr after the initiation of treatment were sterile in all subjects . Survival and complication rates of 95% and 21%, respectively, were observed . This compared favorably to previously published experiences with alternate treatment regimens for Gram-negative meningitis in the newborn . In both meningitis studies, the safety profile for CTX was excellent.(ABSTRACT TRUNCATED AT 250 WORDS) J Protozool, 1989 Jan-Feb, 36(1), 14 - 20 Novobiocin-induced ultrastructural changes and antagonism of DNA synthesis in Trypanosoma cruzi amastigotes growing in cell-free medium; Kerschmann RL et al.; The antimicrobial agent novobiocin, an inhibitor of the bacterial enzyme topoisomerase II (DNA gyrase), is known to antagonize Trypanosoma cruzi amastigotes growing in cell-free medium . To determine sites of antagonism of novobiocin, the effects of drug on parasite ultrastructure and incorporation of radiolabeled precursors of DNA, RNA and protein into macromolecules were determined . The predominant ultrastructural abnormality seen after exposure to 0.40 mM novobiocin for 24 h was the presence of electron-dense clumps in the mitochondrion-kinetoplast organelle in 95 of 257 (37%) of cells, in comparison to no clumps seen in 110 drug-free cells . In addition, in the nucleus, the karyosome was less distinct than in control cells and appeared to merge with the chromatin . In the radiolabeling studies, incorporation of thymidine was inhibited in a dose-dependent fashion by novobiocin (0.16-0.80 mM) in a range of drug concentrations that also inhibited parasite growth . For 0.16 and 0.24 mM novobiocin, incorporation of thymidine was inhibited up to 65% relative to drug-free control cells while uptake of uridine and leucine was unaltered . We interpret these ultrastructure and precursor-incorporation studies as suggesting that (i) the mitochondrion-kinetoplast and possibly the nucleus are sites of novobiocin antagonism of T . cruzi amastigotes and (ii) that novobiocin appears to antagonize DNA synthesis within these organisms . Whether the drug target is topoisomerase II, however, is as yet unknown. Ann Pediatr (Paris), 1989 Jan, 36(1), 39 - 41 {Pleuropulmonary colibacillus infection in a 9-year-old boy leading to the diagnosis of Bruton agammaglobulinemia}; Seaume H et al.; A nine-year-old boy was hospitalized for pneumonia of the left lower lobe . A left pleural effusion developed 48 hours later . The same E . coli strain was recovered from five blood cultures, pleural fluid, and middle ear fluid . Recovery was achieved after two months . Pleural lavage was performed twice daily for the first 15 days and parenteral antimicrobial therapy was given for 45 days . Because E . coli is not usually responsible for ENT or lower respiratory tract infections, an immune deficiency was sought for . The index patient had a twin in whom a history of osteomyelitis at the age of 2 and pneumonia at the age of 8 was found . Recurrent otitis had been a problem in both twins from the age of 14 months . In both twins, immunoglobulin assays led to the diagnosis of Bruton agammaglobulinemia . These two children are now receiving intravenous infusions of human immunoglobulins every three weeks . Bruton agammaglobulinemia is infrequently diagnosed at so late an age. Ann Ophthalmol, 1989 Jan, 21(1), 23 - 8 Uveitis in childhood--Part III . Posterior; Giles CL; Toxoplasma, nematodes, and cytomegalovirus are the most common causes of uveitis in children involving the posterior pole . Discussion of treatment and management is detailed . Rubella retinitis and subacute sclerosing panencephalitis are specific entities which are limited in their initial presentation in children . Panuveitis including sympathetic ophthalmia, Vogt-Koyanagi-Harada, and Behcet's syndromes, while relatively rare in their occurrence, demand early treatment intervention . Specific antimicrobial therapy and adrenocorticosteroids as well as therapeutic suggestions are also included . This is the last part of a three-part series of articles. Bone Marrow Transplant, 1989 Jan, 4(1), 89 - 95 Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse; Weisdorf DJ et al.; Oral mucosal ulceration complicating bone marrow transplantation interferes with patients' comfort, nutrition and may lead to systemic infection derived from the mouth . The mucosal injury results from epithelial damage due to the cytotoxic effects of chemotherapy and radiation conditioning as well as from superficial oropharyngeal infection . Because chlorhexidine gluconate is a broad spectrum topical antimicrobial which has been demonstrably effective in preventing oral infection and gingivitis, we performed a randomized, placebo controlled, double-blind trial of chlorhexidine as a mouth rinse in BMT recipients to study the severity of oral mucositis and both oral and systemic infectious complications . One hundred patients were randomly assigned to receive either chlorhexidine gluconate 0.12% mouth rinse or placebo three times daily from the initiation (day -8) of chemoradiotherapy conditioning until day +35 post-BMT . Chlorhexidine use resulted in a trend toward improved oral hygiene index (reduced dental plaque) (p = 0.06) but did not modify the oral mucositis . Patients using chlorhexidine developed a maximum ulceration of 18 +/- 22% of their oral mucosa, while placebo patients ulcerated 25 +/- 31% of the mouth . Ulcerative mucositis was significantly worse in adults compared with children, in individuals who received methotrexate for graft-versus-host disease prophylaxis, and was most prominent on non-keratinized epithelium . Overall, there was no clinically demonstrable additional therapeutic advantage to the use of chlorhexidine in either reducing the mucositis, controlling oral pain, facilitating oral nutrition, shortening hospital stay, or reducing oral infection with herpes simplex virus . There was a trend toward diminished oral candidiasis in chlorhexidine users (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS) Zentralbl Gynakol, 1989, 111(2), 65 - 77 {Chlamydia infections}; Hoyme UB; Chlamydia trachomatis is a pathogen with an intracellular developmental cycle . Sexually transmitted infection with serotypes D to K can lead to cervicitis, endometritis, salpingitis and urethritis, however, symptoms are commonly mild . Newborns of mothers with cervical infection or colonisation can acquire inclusion conjunctivitis and atypical pneumonia . An efficient prophylaxis is not available so far . Antimicrobial therapy should be initiated as soon as chlamydial infection is confirmed, e.g . with tetracyclines or erythromycin . Partner treatment is mandatory. Rev Infect Dis, 1989 Jan-Feb, 11(1), 46 - 63 Infection due to Actinobacillus actinomycetemcomitans: 15 cases and review; Kaplan AH et al.; Actinobacillus actinomycetemcomitans is a small fastidious gram-negative coccobacillus that fails to grow on MacConkey's agar . Slow growth in broth may lead to delays in diagnosis . First described in 1912, A . actinomycetemcomitans has been recognized since 1962 as capable of causing serious infections in humans . Such infections include periodontal infection, soft tissue abscess (often in association with Actinomyces species), and systemic infection, most commonly endocarditis . Fifteen cases and a review of the English-language literature are presented to define the epidemiology and clinical features of infection due to A . actinomycetemcomitans . Therapy for infection due to A . actinomycetemcomitans has most commonly involved ampicillin or penicillin, often in conjunction with an aminoglycoside . However, resistance to penicillin or ampicillin is common . Antimicrobial agents with a high degree of in vitro activity included cefazolin, cefotaxime, cetriaxone, aminoglycosides, and chloramphenicol . Therapy should be guided by clinical response and in vitro susceptibility testing. Dent Clin North Am, 1989 Jan, 33(1), 91 - 100 Factors influencing periodontal therapy for the geriatric patient; Greenwell H et al.; Anatomic changes in the periodontium occur with aging . There is no indication that these changes predispose to periodontal breakdown . In the United States, there is evidence that older individuals are retaining more teeth and that these teeth have less periodontal disease than previous generations of seniors . Studies comparing the healing of older and younger patients have clearly demonstrated that both groups of patients respond equally well to therapy . Proven methods of periodontal therapy include modified Widman surgery, pocket elimination surgery, or nonsurgical scaling and root planing . Surgical treatment may be used with confidence unless there are medical contraindications . In these cases, nonsurgical therapy may be preferred . If there are physical or mental disabilities that make effective home care difficult, antimicrobial agents, such as the extensively tested chlorhexidine rinse, may be valuable adjuncts . In the future, senior adults can look forward to the benefits of regenerative periodontal procedures that seek to regain lost periodontal support . Age alone should not diminish an individual's right to care because the practitioner has qualms about his or her longevity . Successful treatment of periodontitis by surgical and nonsurgical methods has been extensively documented . Senior patients can benefit from these treatments as much as younger patients, and age is not a barrier to effective periodontal therapy. Medicine (Baltimore), 1989 Jan, 68(1), 38 - 57 Nocardial infections in renal transplant recipients; Wilson JP et al.; Upon review of the English literature and the patients at our hospital, we identified 94 renal transplant recipients with nocardiosis . These patients were further evaluated and compared to nonrenal transplant patients with nocardiosis . We found that these patients were similar in presentation, course, and therapeutic outcome to non-transplant patients . Survival was related to underlying disease, site of infection, rapidity with which the diagnosis was made and, especially, the inclusion of a sulfa compound in the antimicrobial regimen . Transplant centers with high rates of Nocardia infection should consider trimethoprim/sulfamethoxazole prophylaxis for at least the first year after transplantation. Pediatr Hematol Oncol, 1989, 6(1), 17 - 22 Port-A-Cath in children during long-term chemotherapy: complications and outcome; al-Hathal M et al.; Complications related to Port-A-Cath were studied prospectively during a period of 32 months in 31 patients, aged 1-18 years, with leukemias and solid tumors . There were 34 Port-A-Cath inserted, and the cumulative time for these catheters kept in place was 5899 days . No complications occurred in 18 patients (19 catheters) kept in place for a cumulative time of 3998 days with an average duration of 210 days (12-550 days) . In 13 patients (15 catheters) there were 14 events of systemic infections; seven events were treated successfully with antibiotics, four events necessitated the extraction of the catheter (in one patient a combination of systemic and local infection), and in three events the catheters were kept unused, as the patients were in terminal stages . Nonsystemic complications occurred with five catheters; two local infections, two obstructions (catheters removed), and one local bleeding (catheter kept unused) . Appropriate antimicrobial treatment of systemic infections enables the immunocompromised child to keep the Port-A-Cath in place for a long time. Rev Med Chil, 1989 Jan, 117(1), 10 - 7 {Gentamicin and amikacin nephrotoxicity: comparative study in patients with initially normal renal function}; Ballesteros J et al.; The purpose of this study was to compare the nephrotoxic potential of amikacin (AK) and gentamicin (GM) in patients (pts) with normal renal function at the beginning of the treatment (Tx) in an open comparative and prospective trial . Nephrotoxicity (NFTX) was defined as a blood creatinine (Cr) increase of at least 50% from the basal (normal) level, or an increase to higher than normal level during, at the end or after Tx . Peak and trough blood GM and AK levels were determined at 72 h of Tx to make proper adjustments in dosing . The two groups (GM, n = 27 and AK, n = 38) were similar in population composition, underlying pathology and infectious process requiring antimicrobials . Patients in the GM group tended to be older (mean age, 56 years) than the AK (mean age, 48 years) p NS; the latter had received more frequently aminoglycoside Tx (69 vs 11%) p less than 0.0005 . The GM group received a comparatively lower dose than the AK (x = 2.87 mg/k/d and 16 mg/k/d respectively) but duration of Tx was similar . Fifteen of 27 pts receiving GM (56%) and 7 of 38 receiving AK (18.2%) developed NFTX, p less than 0.004 . Five pts in the GM group (18.5%) and 2 in the AK (5.2%) had clinical NFTX . The difference in NFTX persisted after age adjustment . There were no intra or inter group significant differences between pts with or without NFTX . In conclusion, in pts with initial normal renal function gentamicin was significantly more nephrotoxic than amikacin. Acta Vet Scand, 1989, 30(4), 409 - 23 Mycosis in the stomach compartments of cattle; Jensen HE et al.; During a period of 22 months, 9.7% (23 out of 238) of the cattle necropsied at the Department of Veterinary Pathology had mycotic affections in the stomach compartments . The various stomach compartments were affected in the following pattern: omasum: 15 cases, rumen: 10 cases, reticulum: 8 cases and abomasum: 6 cases . In 5 of the animals mycotic affection was also found in other organs of which the liver was most often involved . Out of the 23 cases described, a primary diagnosis of mycosis was only established in 5 cases . In the remaining 18 cases the mycotic infection was regarded as being of a minor importance in the total necropsy result . Macroscopically and histologically the mycotic processes could be grouped into acute, subacute or chronic affections . In 20 cases only one type of inflammation was present, in the remaining cases combinations were found . Identification of the infective agent was performed by immunological staining of hyphal structures in tissue sections . Members of the Zygomycetes were found to predominate as causative fungi . Aspergillus fumigatus was found to have a propensity for infecting the terminal gastric compartments, whereas the Zygomycetes were found regularly in all compartments . Candida spp . were only found in 1 case . Predisposing factors for developing systemic mycosis are discussed . Among these especially the use of antimicrobial drugs, other diseases, metabolic disturbances and stressors in the post parturient period seem to be important. Acta Stomatol Croat, 1989, 23(2), 167 - 74 {Oral lichen ruber}; Cekic-Arambasin A et al.; As oral lichen ruber is quite frequently encountered in contemporary man, dental physicians should be familiar with the characteristics of the disease . Regardless of various forms of the disease, clinical features of lichen ruber may help in making the diagnosis . Recent research on the pathogenesis of the diseases has pointed to a local immune response . An individual diagnostic and therapeutic approach has been imposed by the complex etiology of the disease . In therapy, antimicrobial agents have resumed their place, along with the use of vitamins. Bull World Health Organ, 1989, 67(6), 675 - 84 Monitoring selective components of primary health care: methodology and community assessment of vaccination, diarrhoea, and malaria practices in Conakry, Guinea . ACSI-CCCD team; Dabis F et al.; The Africa Child Survival Initiative-Combatting Childhood Communicable Diseases (ACSI-CCCD) Project is a primary health care activity that focuses on antenatal care, immunization, diarrhoeal disease control, and malaria control in children under 5 years of age . In order to gauge progress made in the project, a community-based health interview survey to measure simultaneously several prevention and treatment indicators was carried out in 1986 in Conakry, Guinea . A sample of 1415 caretakers and their 2048 children aged under 5 years was visited using a cluster sampling technique . The survey documented the levels of literacy and health education awareness of the caretakers, measured the vaccination coverage levels for children and women of childbearing age, and determined treatment practices for diarrhoea and malaria . Of the 637 women who reported having given birth in the previous 12 months, 96% had visited an antenatal clinic, but only 49% had had two or more doses of tetanus toxoid, and 13% took weekly chemoprophylaxis against malaria . The vaccination coverage for measles was 16% for children aged 12-23 months . Oral rehydration therapy (ORT) was given to 16% of children with diarrhoea; however, only 43% of those who were administered ORT at home were treated according to standard guidelines . Of children with diarrhoea, 51% were given antidiarrhoeal or antimicrobial drugs by caretakers . Fever was treated at home for 79% of the febrile children, and 43% of those with fever also visited health units . The use of injectable antimalarials and prolonged treatments with chloroquine were common . Combining findings from a population-based community study with an assessment of practices in health facilities can provide reliable information for the implementation and monitoring of selective components of primary health care. Arch Inst Pasteur Madagascar, 1989, 56(1), 261 - 71 {Study of the antimicrobial action of various essential oils extracted from Malagasy plants . II: Lauraceae}; Raharivelomanana PJ et al.; The microbial growth inhibitory properties of some Lauraceae essential oils, Laurus nobilis, Cinnamomum zeylanicum (cinnamon) and Ravensara anisata were studied by the determination of their respective M.I.C . (Minimal Inhibitory Concentration) . Five bacterial strains, one fungi and two yeasts were used to evaluate the essential oils inhibitory capacities . These vegetable extracts, with decrease activity, were range also: C . zeylanicum--bark greater than R . anisata--bark greater than C . zeylanicum--leaves greater than L . nobilis greater than R . anisata--leaves . The essential oils extracted from cinnamon and R . anisata--bark were very interesting by their antifungic activities. Drugs Exp Clin Res, 1989, 15(10), 465 - 76 Comparative antimicrobial activities of ribostamycin, gentamicin, ampicillin and lincomycin in vitro and in vivo; Inouye S et al.; The antimicrobial activity of ribostamycin, a unique aminoglycoside antibiotic possessing a neutral sugar component, was compared with those of gentamicin, ampicillin and lincomycin in vitro and in vivo . Ribostamycin showed comparable or slightly weaker in vitro activity than the reference antibiotics against Gram-positive bacteria . Against Gram-negative bacteria, ribostamycin was less active than gentamicin, but comparable to or more active than ampicillin . Lincomycin was less active or inactive to Gram-negative bacteria . Ribostamycin was active against some gentamicin-resistant bacteria, especially K . pneumoniae possessing the aminoglycoside-modifying enzymes AAC(3)-l and AAD(2") . The in vivo activity of ribostamycin was weaker than that of gentamicin, but comparable to that of ampicillin and lincomycin against Gram-positive bacteria, and superior to that of ampicillin against Gram-negative bacteria . The in vivo activity of ribostamycin was characterized by (i) and ED50 value not so affected by the challenge inoculum as that of ampicillin; (ii) a lower ED50 value by bolus administration than that by divided administration of the same dosage; and (iii) a lower ED50 value than that expected from the MIC value as compared with that of ampicillin and lincomycin . These characteristics are explained by the rapid and potent bactericidal activity of ribostamycin at high inoculum and high drug concentration, assisted by high serum concentration in mice. Oper Dent, 1989 Spring, 14(2), 77 - 81 Antimicrobial properties of glass-ionomer cements and other restorative materials; Scherer W et al.; The antimicrobial properties of 14 different restorative materials, nine of which were glass-ionomer cements, were compared and observed in this study . The materials were mixed according to manufacturers' specifications and exposed to four types of bacteria commonly found in caries and plaque . Zones of bacterial inhibition were measured for all materials in millimeters . Glass-ionomer cement materials, materials containing zinc oxide, and amalgam produced measureable zones of inhibition. Zentralbl Gynakol, 1989, 111(23), 1549 - 54 {Incidence, causes and follow-up of doubtful smear findings (Papanicolaou group III)}; Hofmann R et al.; Suspect smears of 622 patients from 1977-1986 were analysed for their causes and followed up until the definite cytologic or histologic result . In relation to the overall material of 97,963 cases the rate of suspect smears (group Pap . III) was between 1.18 and 0.27%, i.e . an average of 0.68% . The most frequent reasons for the classification "suspect" were inflammatory (42.4%), metaplastic or degenerative changes (16.1%) and doubtful pre-cancer (30.6%) . 58% of all cases became negative under cytological control and antimicrobial therapy or hormonal substitution; of these 91.4% converted into negative within 6 months . The histological examination carried out on 230 patients revealed pre-cancer (CIN I-III) in 201 cases; cancer was proved in 5 cases . Compared to the whole population that is a rate of 33.1% . 24 cases were to be found negative . 139 Multiparae (67.6%) were to be found in the group of the 206 histological positive cases . 151 women (74%) had taken hormonal contraceptives . The rate of suspect smears should not exceed one per cent. Scand J Infect Dis, 1989, 21(6), 665 - 8 Dental procedures and endocarditis prophylaxis in patients with prosthetic heart valves: results of a questionnaire to 220 patients; Gutschik E et al.; 220 patients with prosthetic heart valves were surveyed regarding dental status, dental health, patient-dentist relationship, information on dental procedures and antimicrobial prophylaxis at the last visit to the dentist . The vast majority of these patients were on life-long anticoagulant treatment because of mechanical heart valve prostheses . Half of the patients had a regular dentist and customarily visited a dentist one or more times a year . One third of the patients were edentulous and 26.5% of the patients indicated dental disease, including chronic periodontitis . Only 30.4% of the patients received antimicrobial prophylaxis in connection with dental extraction and only 13.8% in connection with scaling . Maintenance of good oral health, routine dental checks and better information to the patients and the dentist are called for. Klin Khir, 1989, (10), 1 - 3 {Antimicrobial polymers in surgery of the lungs}; Polous IuM et al.; Approved in the experiment and employed in 60 patients in atypical resection of a lung were the antimicrobial biocompatible absorbable polymers--"Capromed DC threads and ESBADCh film--in combination with MK-7 cyanoacrylate++ glue for formation of hermetic pulmonary suture . This facilitated good smoothing out of the lung remainder, sharp decrease of microbial colonization at the site, where the mentioned polymers were used. Ann Med Interne (Paris), 1989, 140(7), 593 - 6 {Drug-induced pneumopathies (excluding cytostatic drugs)}; Akoun G et al.; Establishing the diagnosis of drug-induced pneumonitis is always difficult and requires that the following criteria be met: administration of the drug on a long-term basis; knowledge that the drug is able to induce pulmonary disorders; occurrence during therapy of interstitial pneumonitis with clinical, radiological and functional characteristics of this type of lung disease; exclusion of all other causes of interstitial pneumonitis (cardiac failure, infections, collagen vascular diseases, malignancies); bronchoalveolar lavage specimen, revealing lymphocytosis with an inverted CD4/CD8 lymphocyte ratio, isolated or associated with neutrophil and/or eosinophil alveolitis; finally, full recovery within several weeks or months after drug withdrawal unless irreversible pulmonary fibrosis has occurred . Certain specific characteristics correspond to the therapeutic class of the drug, i.e . antimicrobial, cardiovascular, antiinflammatory, neurological, metabolic, antiallergy or some other drugs. Pharmacology, 1989, 39(4), 213 - 23 Effects of 2(3)-tert-butyl-4-hydroxyanisole pretreatment on cefpiramide binding to mouse glutathione S-transferases; Nishiya H et al.; Binding of cefpiramide (CPM) and other beta-lactam antimicrobial agents to 2(3)-tert-butyl-4-hydroxyanisole (BHA)-induced liver glutathione (GSH) S-transferases (EC 2.5.1.18) from CD-1 mice was studied . A marked induction of hepatic GSH S-transferase from mice fed BHA was observed . Gel chromatography of liver cytosol from mice fed BHA showed an increased binding of CPM, cefotetan and cefazolin to BHA-induced GSH S-transferases . The extent of their binding to GSH S-transferase seemed to be correlated with the extent of their excretion into the bile . Binding of CPM to the GSH S-transferase fraction was inhibited by both indocyanine green, which is known to bind liver GSH S-transferases intensively, and by cefoperazon, which is mainly excreted into the bile . This study suggests that GSH S-transferases are the main binding proteins of CPM in the liver cytosol fraction and play an important role as carrier proteins of CPM and some antimicrobial agents in mouse liver. Pediatr Radiol, 1989, 20(1-2), 76 - 9 Physeal involvement in chronic recurrent multifocal osteomyelitis; Manson D et al.; Chronic recurrent multifocal osteomyelitis is a recently recognized disease characterized by remissions and exacerbations of multiple bone lesions which radiographically and pathologically have the appearance of hematogenous osteomyelitis . No consistent etiology can be identified, and antimicrobial agents seem to have no beneficial effect . A review of the appearances on imaging modalities and the clinical and pathologic manifestations is undertaken in seven cases of CRMO . No therapeutic regimen resulted in consistent clinical or radiographic improvement . We suggest the sequelae of this process are not as benign as previously reported. Arch Oral Biol, 1989, 34(7), 499 - 506 Relationships between human parotid saliva lysozyme lactoferrin, salivary peroxidase and secretory immunoglobulin A in a large sample population; Rudney JD; Saliva antimicrobial proteins may interact in a common system for host defence . This study applied multivariate analysis as a means of describing inter-person variation in that system . Samples of stimulated parotid saliva were obtained from 198 subjects . Flow rate was determined, and assays run for total protein, lysozyme, lactoferrin, salivary peroxidase and secretory IgA . Correlation and principal components analysis were used to define the relationships between proteins; cluster analysis was used to identify persons with similar protein concentration profiles . All proteins were significantly correlated at p less than 0.002 (r = 0.20-0.52) . Principal components analysis identified a major axis of common variation, defined by lysozyme and salivary peroxidase, and a second axis, defined by secretory IgA . Lactoferrin was associated with both axes . Seven major groupings were obtained by cluster analysis; these were significantly different at p less than 0.001 . Such groupings may prove useful in comparing the antimicrobial properties of saliva samples. Ter Arkh, 1989, 61(8), 113 - 6 {The efficacy of the natural antibacterial preparation chlorophyllypt in the combined treatment of acute lung abscesses}; Nikitin AV et al.; The complexity of the treatment of acute suppurative pulmonary diseases has been aggravated recently by the growth of microbial resistance to antibiotics and enhancement of the allergy incidence among the population . This circumstance restricts the use of antibiotic on a broad scale in clinical practice and makes the researchers go in studies of adequate substitutes . In the given case, use was made of chlorophyllipt . It was given to patients by intravenous drip in the form of a 0.25% solution based on saline twice a day . To increase local deposition of the administered antimicrobial drug in the affected area, interstitial electrophoresis was employed . In the patients' group on chlorophyllipt, the clinico-laboratory and x-ray parameters returned to normal earlier . Chlorophyllipt was noted to produce an immunocorrective action characterized by the normalization of the absolute count and percentage of E-RFC and theophylline-resistant-RFC . This action could not be observed in the patients' group receiving only antibiotics. Adv Perit Dial, 1989, 5, 103 - 10 Ca++ and 1,25(OH)2D3 enhance peritoneal macrophage (PMPhi) antimicrobial functions in CAPD; Carozzi S et al.; Ca++ has been proposed as an intracellular second messenger for the activation of immune cells . An immune regulatory role for 1,25(OH)2D3 has also been suggested . We therefore evaluated the role of Ca++ and 1,25(OH)2D3 in the depressed antibacterial functions of 8 CAPD patients with relapsing bacterial peritonitis by evaluating in vitro the effects of escalating concentrations of 1,25(OH)2D3 and/or Ca++ on: 1 . peritoneal macrophage (PMO) cytoplasmic Ca++; 2 . PMO superoxide generation; 3 . PMO leukotriene B4 release, 4 . PMO bacterial killing . Results showed a dose-dependent increase in all parameters for Ca++ concentrations from 500 to 3,000 microM while with both a CA(++)-free medium and with Ca++ concentrations of 5,000 microM of medium all the aforementioned functions were abrogated . Addition of low doses of 1,25(OH)2D3 strongly potentiated the stimulatory effect of Ca++ on cell functions, while high doses were inhibitory . These in vitro data underline the importance of Ca++ and 1,25(OH)2D3 in PMO antibacterial functions in CAPD patients, and may be useful in the prophylaxis and therapy of peritonitis. Acta Derm Venereol, 1989, 69(3), 223 - 6 Cutaneous drug reactions: clinical types and causative agents . A five-year survey of in-patients (1981-1985); Alanko K et al.; We collected a 5-year series of drug eruptions . There were 225 cases, 128 of them verified by a positive provocation test . The most common types of clinical reaction were fixed drug eruptions, exanthematous eruptions and urticarias . The drugs most often responsible for the eruptions were antimicrobial agents and antipyretic/anti-inflammatory analgesics . Comparing this series with our three previous series from the same hospital, the total number of drug eruptions proved to have decreased over the last 30 years . The main groups of drugs causing skin reactions have remained the same, but in recent years the proportion of sulphonamides has diminished. Gan To Kagaku Ryoho, 1989 Jan, 16(1), 1 - 8 {Anti-tumor natural products isolated from marine organisms}; Kitagawa I et al.; Marine organisms comprise over half a million species . Due to their unusual living environment as compared with terrestrial organisms, marine organisms produce a variety of metabolic substances which often have various unprecedented chemical structures . In recent years, an increasing number of marine natural products have been reported to exhibit various biological activities such as antimicrobial, physiological, and pharmacological ones . Some metabolites have also been noted by their significant toxicities . The effort to find out anti-tumor substances from marine organisms has been also undertaken in recent years, and several novel compounds (e.g . peptide, polyether, alkaloid, prostanoid etc.), with anti-tumor activities, have been isolated from marine sponges, octocorals, marine algae, tunicates, nudibranchs, bryozoans, and so on . In this article, those chemically clarified anti-tumor compounds isolated from marine organisms were reviewed. Bull Hosp Jt Dis Orthop Inst, 1989 Spring, 49(1), 107 - 10 Nocardia asteroides infection of an Austin-Moore hemiarthroplasty in a nonimmunocompromised host . A case report; Robinson D et al.; A case of Nocardia asteroides infection of a hip prosthesis in a nonimmunocompromised patient is presented . The infection developed soon after the operation, and did not respond to empiric treatment by multiple antimicrobial drugs . Reoperation and removal of the prosthesis was necessary . The authors found no previous cases of nocardiosis complicating arthroplasty reported in the literature. Fortschr Ophthalmol, 1989, 86(2), 164 - 6 {The peroxidase content of human tears}; Buchberger W et al.; The peroxidase-(POD)-thiocyanate-hydrogenperoxide-system is a well-known antibacterial system, which has been demonstrated to exist, for example, in milk and saliva . Earlier investigations by van Haeringen et al . established a POD level in human tears of 10(3) units/l, yet the thiocyanate concentration was only about 0.2 mmol/l . Therefore van Haeringen et al . excluded the existence of a POD-thiocyanate-hydrogenperoxide antibacterial system in human tears because of the insufficient amount of thiocyanate in the tears examined . Instead of thiocyanate halides such as J- can also complete the POD hydrogen peroxide system as electron donors . Sufficient amounts of iodide can be expected after the application of iodine-containing eye drops or after local treatment with iodine-containing brine, as done in Bad Hall in Austria . Therefore, the above mentioned antibacterial system may be of importance if the POD-level is high enough (greater than 250 units/l) . We investigated 22 tear samples from healthy persons: the POD levels were below 20 units/l in 19 cases; in 3 cases the POD concentration was found to be between 20 and 50 units/l . Therefore, in normal human tear fluid, not only the amount of thiocyanate but also the concentration of POD is too low for effective antimicrobial activity of the peroxidase-thiocyanate-hydrogenperoxide system . It is so far not known whether this system is effective under pathological conditions. Antibiot Khimioter, 1989 Jan, 34(1), 20 - 4 {Structural and functional investigation of polymyxins . Structure and biological properties of polymyxin M analogs}; Trakhanova MN et al.; The effect of proteinases of plant and microbial origin on polymyxin M was studied . It was shown that this antibiotic was absolutely stable to the effect of papain and ficin . On hydrolysis with subtilisin there formed polymyxin decyclized analogs not described earlier . Their isolation, purification and biological activity are described . The structure of these compounds was assessed by one- and two-dimensional 1H NMR spectroscopy . The role of various functional groups, their space orientation and impact on antimicrobial activity of the compounds are discussed. Biochem Pharmacol, 1989 Jan 1, 38(1), 161 - 5 The inhibitory effect of acetaminophen on the myeloperoxidase-induced antimicrobial system of the polymorphonuclear leukocyte; van Zyl JM et al.; Acetaminophen binds via its acetamido side chain to purified myeloperoxidase in a pH-dependent manner and maximum binding occurred around pH 6 . The H2O2-dependent myeloperoxidase-catalysed polymerization products of acetaminophen had excitation maxima at 304 nm and 334 nm in acid and alkaline solutions, respectively, and an intense blue fluorescence maximum at 426 nm . Acetaminophen can compete effectively with Cl- as myeloperoxidase substrate and thus HOCl formation is suppressed while HOCl, nevertheless present, can be scavenged by the drug . In this way the microbicidal action of the myeloperoxidase-H2O2-Cl- system can be seriously limited in the presence of high concentrations of acetaminophen . To study the effect of acetaminophen on peptide bond splitting in the myeloperoxidase antimicrobial system, thyroglobulin was used as a model peptide . Peptide bond splitting was inhibited at acetaminophen concentrations below the accepted toxic range for plasma values. Acta Derm Venereol Suppl (Stockh), 1989, 143, 14 - 9 Pharmacology and toxicology of azelaic acid; Topert M et al.; The results of general pharmacological studies on metabolism, smooth muscles, renal function, cardiovascular and neurotropic effects do not contra-indicate the specific surface use of azelaic acid . From specific pharmacologic studies it is assumed that azelaic acid exerts its therapeutic effect in acne by an antimicrobial, probably bacteriostatic, effect on acne-relevant microorganisms such as Propioni bacerium acnes and, in addition, by a strong comedolytic effect . In numerous studies it has been demonstrated that azelaic acid is not toxic. Zahn Mund Kieferheilkd Zentralbl, 1989, 77(2), 128 - 30 {Experimental research on the genotoxicity of various root canal antiseptics in the SOS chromotest}; Klimm W et al.; The genotoxicity of the endodontic antiseptics chlorhexidine digluconate, chloramine and sodium hypochlorite was determined by SOS chromotest using Bioscreen Analyzer Systems (Labsystem OY) . All antiseptics did not show a genotoxic effect . Chlorhexidine digluconate was the most efficient antimicrobial agent against E . coli PQ 37. J Antimicrob Chemother, 1989 Jan, 23(1), 37 - 41 Susceptibility of Legionella pneumophila to eight antimicrobial agents including four macrolides under different assay conditions; Liebers DM et al.; A comparison of agar dilution and microdilution susceptibility testing for eight antimicrobial agents, including roxithromycin, was performed against 48 isolates of Legionella pneumophila . For agar dilution tests, charcoal free agar (BSYE) and charcoal supplemented agar (BCYE) were used . In general, BSYE agar produced lower MICs than BCYE agar, except for imipenem . Microdilution testing data fell between the data obtained for the two agar media . The MBCs were two to sixteen fold higher than the MICs . Prolongation of the incubation time from 48 h to 72 h or growth in 5% CO2 did not influence the results . As tested by the microdilution method, an increase in the inoculum from 10(5) to 10(7) was associated with a two-fold increase in the MIC . Roxithromycin and two other investigational macrolides (A-56268 and rosaramicin) demonstrated better in-vitro activity than erythromycin. J Periodontal Res, 1989 Jan, 24(1), 75 - 80 The effect of a dentifrice containing zinc citrate and Triclosan on developing gingivitis; Saxton CA et al.; A partial mouth experimental gingivitis model was employed to establish the potential efficacy of a dentifrice containing a zinc salt and the antimicrobial agent Triclosan to prevent or delay the development of gingivitis over a period of 28 days . Initially, gingival health was established in 34 subjects following a 6-week period of professional tooth cleaning and oral hygiene instruction . A toothshield was constructed to fit 4 posterior mandibular teeth . Undiluted test or placebo dentifrice was applied to the experimental teeth via the toothshield, which also prevented plaque removal from these teeth during habitual brushing of the remainder of the dentition . The presence of plaque, bleeding after probing and visual signs of inflammation were independently assessed . Plaque accumulated rapidly and gingivitis developed in both groups . At the 2-wk assessments, lower mean plaque scores were recorded for the group using the test dentifrice . At the 4-wk assessment a significantly lower level of gingivitis was recorded for the test group . It is concluded that (a) the model can be used to establish the potential efficacy of a dentifrice to maintain gingival health, (b) the dentifrice containing zinc citrate and Triclosan was efficacious and (c) the Gingival Index possibly overestimates the proportion of healthy gingival sites. Cell Immunol, 1989 Jan, 118(1), 229 - 33 Aging and immunity to tuberculosis: prolonged survival of old mice infected with Mycobacterium tuberculosis by adoptive immunization with memory-immune T lymphocytes; Orme IM; This study shows that memory immune T lymphocytes, harvested from young (3-month-old) mice infected intravenously with Mycobacterium tuberculosis and then exposed to protracted chemotherapy with isoniazid, are capable of adoptively protecting old (24 month) mice from a subsequent fatal challenge infection . Survival of such adoptively protected animals was prolonged, but did not extend beyond the mean survival time of uninfected old control mice . During this time the passively transferred memory T cell population retained their functional capacity to protect against subsequent tuberculosis infection . These data indicate, therefore, that reconstitution of decayed cell-mediated antimicrobial immunity in old mice in vivo with memory T cells is technically feasible, although the life span of the animal is not extended over that of control animals . They indicate, moreover, that the memory T cells remain functional in what some reports have considered a suppressive environment and show further that the macrophages with which the infused T cells interact in the aged host remain functionally able to express acquired resistance. G Batteriol Virol Immunol, 1989 Jan-Dec, 82(1-12), 165 - 73 {Evaluation of in vitro antibiotic sensitivity: critical features of the MIC}; Malcangi A et al.; Current methods for the "in vitro" study of antibiotic activity, as minimum inhibitory concentration, expose bacteria to constant concentrations of antibiotics . The "in vivo" situation is significantly different, since the antibiotic concentration changes with time . Pharmacokinetic models are "in vitro" experimental systems that seek to simulate conditions of exposure of bacteria to antimicrobial agents that exist in blood and tissues . All of these systems are complicated constructions . A new simple "in vitro" kinetic model, based on solid phase growth, is described. Braz J Med Biol Res, 1989, 22(9), 1127 - 9 Antimicrobial activity of kaurenoic acid derivatives substituted on carbon-15; Davino SC et al.; The antibacterial and antifungic activities of two kaurenic acids, ent kaurenoic acid and cinnamoylgrandifloric acid isolated from a hexane extract of aerial parts of Mikania laevigata, were investigated and compared with the activities of other kaurenic acid derivatives substituted on carbon-15 . Only acetylgrandifloric acid (ent-kaur-16-en-15 alpha-acetyloxy-19-oic) and its epimer xylopic acid (ent-kaur-16-en-15 beta-acetyloxy-19-oic) displayed significant antibacterial activity at concentrations greater than or equal to 250 micrograms/ml, the 15 alpha epimer being the most active. Acta Pol Pharm, 1989, 46(4), 337 - 42 {Synthesis of phosphobetaine--a derivative of long-chain tertiary aliphatic amine with epichlorohydrin}; Marcoin W; Synthesis of a new surface active agent, a phosphobetaine derivative of tertiary amines with C12-22 long chains and sodium 3-chloro-2-hydroxypropyl phosphate has been elaborated . The reactants were applied at the molar ratio of 1:1.3 . The obtained compounds was found to possess high surfactant and antimicrobial activities. Eur J Clin Microbiol Infect Dis, 1989 Jan, 8(1), 40 - 50 Nosocomial pneumonia in the intubated patient: role of gastric colonization; Craven DE et al.; A high rate of nosocomial pneumonia exists among intubated patients receiving mechanical ventilation . Retrograde colonization of the oropharynx and trachea with bacteria from the stomach is not widely appreciated in the pathogenesis of pneumonia . Gastric colonization is affected by age, malnutrition, antibiotics, disease of the gastrointestinal tract, and changes in pH . The widespread use of antacids and/or histamine type 2 blockers as prophylaxis against stress bleeding in the ventilated patient may also increase gastric pH and the risk of colonization in the upper gastrointestinal tract . Migration of bacteria between the stomach, oropharynx and trachea in the intubated patient may be a dynamic system involving large numbers of bacteria . The high fatality rate of mechanically ventilated patients with pneumonia, which persists despite treatment of these patients with appropriate antimicrobial therapy, underscores the need for effective measures of prevention . Preventive measures include the appropriate use of antibiotics, proper decontamination of respiratory therapy equipment, the cautious use of drugs that alter the natural gastric acid barrier, or, possibly, the selective use of antibiotics to prevent or reduce gastric, oropharyngeal and tracheal colonization. Eur J Clin Microbiol Infect Dis, 1989 Jan, 8(1), 35 - 9 Diagnosis of nosocomial pneumonia in intensive care unit patients; Chastre J et al.; The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation . An important advance has been the development of the protected specimen brush technique . We and others have demonstrated that secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia . However, this procedure has important limitations in that results are not available immediately and in that a few false negative or false positive results may be observed . Recently, the use of bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, since the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture . We believe that microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for early and rapid diagnosis of pneumonia in this setting and that the lavage technique can be conveniently incorporated into a protocol along with the quantitative culture of samples obtained using the protected specimen brush . This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in the majority of patients with pneumonia. JPEN J Parenter Enteral Nutr, 1989 Jan-Feb, 13(1), 92 - 8 Treatment of an infected silicone right atrial catheter with combined fibrinolytic and antibiotic therapy: case report and review of the literature; Lewis JA et al.; Tunnelled silicone rubber right atrial catheters are commonly used to administer long-term total parenteral nutrition (TPN), cancer chemotherapeutic agents, and antimicrobial agents . The indwelling devices potentiate platelet-fibrin thrombi formation, providing a nidus for infection . Although many episodes of sepsis associated with thrombotic tunnelled catheters respond to antimicrobial therapy alone, a significant number require catheter removal . Evidence from case studies and small clinical trials suggests that fibrinolytic agents may increase the response rate and prevent removal of the device when combined with antimicrobial therapy . We present the first case reported of bacterial sepsis secondary to a thrombotic indwelling Hickman catheter for long-term TPN successfully treated with a combination of streptokinase and antibiotic therapies. Chin J Biotechnol, 1989, 5(3), 161 - 6 Interspecific protoplast fusion of Streptomyces hygroscopicus var . yingchengenisis with Streptomyces qingfengmyceticus and biological characterization of their recombinants; Zhou XF et al.; The frequency of recombination between Streptomyces hygroscopicus var . yingchengensis and Streptomyces qingfengmyceticus as a result of interspecific protoplast fusion was 4.5 x 10(-4) . Characterization of biological properties revealed differences in spore mass color, drug resistance, antimicrobial activity, and antibiotic production capacity between the recombinants and their parents . Two recombinant strains, FL-42 and FL-48, exhibited production of the antibiotics originally elaborated by the two parents individually . They also produced two compounds with antimicrobial activity that their parents could not synthesize. G Batteriol Virol Immunol, 1989 Jan-Dec, 82(1-12), 92 - 6 {Various biotypes of Escherichia coli: their correlation with antibiotic resistance}; Molinari GL et al.; The antimicrobial susceptibilities of 572 strains of Escherichia coli were evaluated . The strains were divided according to the biotypes and the differences between the strains towards various antibiotics were examined . We found a correlation between biotype and antibiotype . This correlation lead us to think of a possible existence of more resistant biotypes than others . Now we are doing other studies in order to show if this correlation is constant during time and if similar differences are present for other microorganisms, as well. J Pharm Biomed Anal, 1989, 7(9), 1011 - 32 Advances in liquid chromatography and related methodologies for therapeutic drug monitoring; Wong SH; In this article the merits of current liquid chromatography (LC) columns and techniques are reviewed, to include the following topics: (1) a brief introduction to rational therapeutic drug monitoring (TDM) to justify drug measurements; (2) selected recent survey results from the College of American Pathologists (CAP) to establish the current utilization pattern of LC for TDM in the USA; (3) LC analyses of major classes of drugs--antiarrhythmics, antidepressants, antiepileptics, antimicrobials, cyclosporine, and others--with emphasis on analysis of these drugs in human serum or plasma, by focusing on the less usual, reversed-phase functional groups such as CN and phenyl, and by the use of "mini" columns, silica and polymeric columns, the emphasis being reduced on the well-established C-18 columns; (4) high-speed LC; (5) various approaches of direct sample analysis--solvent extraction, automated sample processing, column switching, micro-injections, micellar chromatography, electrochemical detection with photolytic derivation, and the internal surface reversed-phase column of Pinkerton; (6) microbore LC drug analysis; (7) clinical chiral separation; and (8) overall conclusions. Lens Eye Toxic Res, 1989, 6(1-2), 59 - 85 An in vitro method which assesses corneal epithelial toxicity due to antineoplastic, preservative and antimicrobial agents; Lazarus HM et al.; We developed an in vitro model for studying the cytotoxicity of pharmacologic agents on corneal epithelium employing 3H-thymidine incorporation . Primary rabbit corneal epithelial cell cultures were established, and the cells plated prior to each experiment . 3H-thymidine incorporation was measured after the addition of drug or vehicle to these confluent cells, and dose-response curves were generated . Marked inhibition of 3H-thymidine incorporation was reached at chemotherapeutic concentrations achieved clinically for cytosine arabinoside (10(-7) M), methotrexate (10(-3) M), and 5-fluorouracil (10(-6) M) . A 10(-4) M concentration of 2-deoxycytidine, a naturally occurring competitive inhibitor of cytosine arabinoside, protected cells up to a concentration of 10(-5) M . We utilized these data to undertake an in vivo prophylaxis study in 13 leukemia patients receiving high-dose iv cytosine arabinoside . Topical deoxycytidine 10(-4) M and 1% prednisolone phosphate, given 12 hours prior to the start of antileukemic therapy, were effective in reducing symptoms and signs of keratitis; both were better than historical placebo-treated eyes . Ophthalmic preservatives were studied in vitro at concentrations used clinically: benzalkonium chloride (BAC) (0.004-0.02%) was the most toxic, thimerosal (TMS) (0.001-0.004%) intermediate, and chlorobutanol (CHB) (0.2-0.5%) the least toxic . Antiviral agents (final concentration) included: trifluridine (TFT) (1.0%), ethyldeoxuridine (EDU) (2.0%), and idoxuridine (IDU) (0.1%) . Dose but not time-dependent concentrations of these 3 agents were noted to cause toxicity; however, (E)-5(2-bromovinyl)-2'-deoxyuridine (BVDU) (0.1%) was non-toxic . Similarly, tobramycin and amikacin were significantly less toxic than gentamicin and neomycin in this system . These in vitro cytotoxicity data correlate well with previous in vivo and pre-clinical corneal epithelial toxicity studies . Our model may be useful in the toxicologic study of future topical ophthalmic agents. Acta Paediatr Scand Suppl, 1989, 361, 31 - 43 Iron-binding proteins; Brock JH; The structure and properties of the iron-binding proteins transferrin, lactoferrin and transferrin are reviewed . Transferrin and lactoferrin are structurally similar, consisting of a single polypeptide chain and reversibly binding two iron atoms per molecule . Transferrin is found mainly in serum, whereas lactoferrin is found in neutrophils and in external secretions . Transferrin functions mainly as a donor of iron to cells, but there is no established iron-transport role for lactoferrin . Both these proteins may have antimicrobial activity as a result of their ability to sequester iron . Lactoferrin may act principally as a scavenger of iron in conditions where transferrin may not bind iron well, e.g . at low pH . Ferritin is a multisubunit protein capable of binding up to 4,000 iron atoms and serves principally as an iron-storage protein, though it may also serve to detoxify iron . In iron-rich tissues ferritin is largely degraded and the iron is converted to haemosiderin. Int J Biochem, 1989, 21(5), 463 - 8 Effect of pisiferic acid and its derivatives on cytotoxicity macromolecular synthesis and DNA polymerase alpha of HeLa cells; Kobayashi K et al.; 1 . Seventy-seven derivatives of pisiferic acid (2), an antimicrobial diterpenoid, were tested for cytotoxicity against HeLa cells and 9 derivatives were found to show cytotoxicity at less than 2 micrograms/ml dose (IC50) . 2 . Hydrophobicity was revealed to be an important factor for cytotoxicity of the derivatives . 3 . Compound 2 inhibited predominantly DNA synthesis in HeLa cells as compared with RNA and protein synthesis . 4 . No direct interaction between 2 and nucleic acid bases was indicated by a u.v . spectral method . 5 . Several of the pisiferic acid species showed inhibitory action on HeLa DNA polymerase alpha, and the inhibitory activity was about 1/20 of aphidicolin. J Leukoc Biol, 1989 Jan, 45(1), 29 - 34 Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes; Carlin JM et al.; Interferon (IFN)-induced tryptophan degradation, catalyzed by indoleamine 2,3-dioxygenase (IDO), has been shown to mediate antimicrobial activity in epithelial cells . IDO activity has also been augmented in peripheral blood mononuclear cells (PBMC) treated with IFN or interleukin-2 (IL-2) . The effector cells in this population have now been further characterized . PBMCs were isolated from normal donors, separated into monocyte and lymphocyte populations by plastic adherence, treated with IFN or IL-2, and cultivated in medium supplemented with {3H}tryptophan . Culture supernatants were collected after a 48-h incubation and fractionated by high-performance liquid chromatography; radioactivity was determined in fractions corresponding to tryptophan and its metabolites . IFN-gamma and IFN-beta induced IDO activity only in monocytes (plastic-adherent, nonspecific esterase-positive PBMCs) . The induction of IDO activity by IL-2 required both monocytes and lymphocytes . Interaction was required between these populations for induction of IDO by IL-2, due to production of IFN-gamma by T lymphocytes, with subsequent IFN-gamma-mediated induction of IDO in monocytes . A number of myeloid cell lines as well as monocyte-derived macrophages were also tested for their ability to be induced to degrade tryptophan in response to IFN treatment . Monocyte-derived macrophages were found to retain their capacity to be induced by IFN-gamma and IFN-beta to degrade tryptophan after differentiation, and to possess seven times more IDO activity per cell than IFN-induced monocytes . However, the presence of lipopolysaccharide (LPS) in the culture medium was required for the maximum induction of IDO activity by IFN-beta . Furthermore, higher concentrations of LPS were sufficient to induce IDO activity in macrophages in the absence of exogenous IFN. Z Gesamte Inn Med, 1988 Dec 15, 43(24), 713 - 4 {Principles of modern antibiotic therapy in the general practice and clinic . Discussion of the contribution by Walter Siegenthaler and Gertrude Siegenthaler-Zuber published in Z . gesamte inn . Med . 42 (1987) 614-618}; Tauchnitz C et al.; W . Siegenthaler's and G . Siegenthaler-Zuber's opinion, according to which in the majority of infections in practice an etiological (microbiological) diagnosis may be renounced and the guiding slogan "before therapy the gods have placed the diagnosis" should be relativized for the situation in the practice in contrast to the situation in the clinic, is opposed . Microbiological findings represent an unrenouncable basis for a rational antimicrobial chemotherapy in practice and clinic . In the individual case this does not exclude a calculated chemotherapy on account of a clinical and microbiological tentative diagnosis made by the physician in charge . But at the latest when the empiric therapy fails an efficient microbiologic diagnostics must be at our disposal. Hosp Pharm, 1989 Jan, 24(1), 26 - 9, 32 Pharmacy-laboratory interactions: a unique method to control antibiotic costs; Goff D et al.; Because a large percentage of hospital antibiotic use is regarded as inappropriate, hospital pharmacists must investigate ways of decreasing such usage . A unique approach was evaluated for its impact on cost-effective antibiotic therapy . By functioning as a team, the pharmacy and laboratory departments implemented the following steps: cost-code index on antimicrobial susceptibility and organism identification reports; suppression of cost-ineffective antibiotics within the same pharmacologic group from the antimicrobial susceptibility reports; design of minimum inhibitory concentration panels to conform to the hospital formulary; daily delivery of the antimicrobial susceptibility reports to the pharmacy . Of the 1078 documented therapeutic interventions by the clinical pharmacist, 100 were randomly selected for review, 62% of which involved direct interaction with the laboratory . Estimated cost savings due to these interactions were $8214; annual savings were $88,554 . The results of this study show the importance of pharmacy departments forming and maintaining lines of communication with the hospital laboratory department. Hosp Formul, 1989 Jan, 24(1), 41 - 4, 46 Impact of a two-stage intervention program on cefazolin usage at a major teaching hospital; Gupta S et al.; To reduce antimicrobial drug costs associated with the administration of cefazolin, a two-stage therapeutic intervention--employing persuasive (informational) and power (therapeutic interchange) strategies--was initiated at this 1,000-bed major Canadian teaching hospital . The target of the intervention was to extend the dosage interval of cefazolin to q8h . During a 12-week preimplementation period, 32% of orders specified 8-hour dosage intervals . This percentage increased to 58% after the 3-week, initial informational stage of the intervention . When therapeutic interchange was employed, the percentage of orders for extended intervals rose to an average of 97% over a 32-week postimplementation period . An estimated annual cost savings of $58,000 resulted from this intervention . Manpower requirements to implement and maintain this program were minimal and prescriber antagonism was not encountered. Mech Ageing Dev, 1988 Dec, 46(1-3), 29 - 32 An age-related loss of the isogeneic barrier to the successful passive cell transfer of antimicrobial immunity in mice; Orme IM; The results of this study show that an isogeneic barrier to the successful adoptive immunotherapy of Mycobacterium tuberculosis infected mice is progressively lost as these animals age . This was shown in this study by the demonstration that increasing levels of transferred acquired specific resistance could be conferred on normal old recipients of greater than 22 months of age, whereas in young recipients such transfers were unsuccessful without the prior exposure of recipients to sublethal levels of whole-body ionizing gamma irradiation . These data indicate that strategies of adoptive immunotherapy in the elderly may not have to overcome the age-related isogeneic physiological barrier to this procedure. Chemioterapia, 1988 Dec, 7(6), 369 - 72 Antibiotics and immunity: effects of antibiotics on mitogen responsiveness of lymphocytes and interleukin-2 production; Ibrahim MS et al.; The immunomodulating properties of antimicrobial drugs may have important implications in prescriptive practice . This is particularly so for patients whose immune system has been compromised . In this study, tetracycline, cephalothin, rifampicin, polymyxin B and nitrofurantoin reduced mitogen responsiveness of both B and T lymphocytes of mouse spleen cells and human peripheral blood lymphocytes in vitro in a dose-dependent fashion . Ampicillin, chloramphenicol, gentamicin, streptomycin and erythromycin had no effect . In the in vivo study none of the antibiotics affected mouse spleen cell tran