Pharmacoeconomics, 1994 Jan, 5(1), 56 - 77 Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF): an appraisal of its pharmacoeconomic status in neutropenia associated with chemotherapy and autologous bone marrow transplant; Goa KL et al.; Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) expedites neutrophil recovery in cancer patients receiving chemotherapy with or without autologous bone marrow transplant (ABMT) . The limited cost analyses available in patients undergoing ABMT support a cost reduction of about 25 to 35% with rGM-CSF therapy, relative to placebo, generated primarily by decreases of 20 to 30% in hospitalisation costs reflecting reductions in length of hospitalisation . Results of 1 trial show equivalent cost savings of 40% versus placebo with either rGM-CSF or recombinant granulocyte colony-stimulating factor (rG-CSF) in patients with chemotherapy-induced febrile neutropenia . Whether reduced infection rates seen with rGM-CSF may lessen costs of antimicrobial therapy is undetermined; however, a 16% decrease in this cost factor was reported in 1 evaluation of high dose chemotherapy with ABMT . No analyses have assessed the cost effectiveness of rGM-CSF as prophylaxis in patients receiving chemotherapy . Survival rates have increased in patients treated with rGM-CSF after bone marrow graft failure . In contrast, with the exception of one small trial, improvements in mortality or relapse rates have not occurred with rGM-CSF used prophylactically with chemotherapy, despite favourable effects on neutrophil recovery and facilitation of dose-intensified chemotherapy regimens . Similarly, survival has not increased in patients undergoing ABMT . The long term economic impact of rGM-CSF in these indications is thus unknown . Other factors predicted to produce modest cost savings include possible reductions in expenditure related to treating mucositis, and lowered transfusion requirements in some patients . Whether rGM-CSF may provide benefits in other areas that can be expressed in economic terms, such as quality of life, also remains to be established . On the whole, rGM-CSF has a good tolerability profile, obviating the need for costly monitoring procedures . Like other expensive biotechnology products, its cost effectiveness will be aided by implementation of appropriate prescribing techniques and protocols to minimise wastage . Thus, at present rGM-CSF therapy appears to offer a means of reducing hospitalisation costs, and therefore a substantial component of treatment expenditure, in patients undergoing ABMT or with chemotherapy-induced febrile neutropenia. Lancet, 1993 Dec 4, 342(8884), 1415 - 6 STD research in Africa; Grosskurth H et al.; PIP: The control of sexually transmitted diseases (STDs) is vital to combat AIDS in developing countries . The 1993 World Development Report showed the cost effectiveness of STD control per healthy life-year saved . A meeting of the Network of AIDS Researchers in East and Southern Africa was held on this issue in Mwanza, Tanzania, attended by 20 experts from 5 countries in the region . The World Health Organization recommends that STDs should be managed without laboratory tests, at the primary health care level in developing countries, using drugs of proven local efficacy . In Africa, this policy has been implemented only in Zimbabwe, but without a striking fall in STDs, since in 1991 STDs were responsible for over 20% of visits by adults at primary health care clinics in Harare . A contact-tracing study in Harare indicated that only 20 contacts were found after 3 months' work by 6 staff members . Asymptomatic STDs in women have hampered STD control, but a community study from Mwanza has also shown that 6% of men were infected with gonorrhea or chlamydia and 90% had no symptoms . A WHO risk-assessment protocol is being evaluated in Mwanza among women with vaginal discharge . A controlled trial of mass treatment for gonorrhoea, chlamydia infection, chancroid, and syphilis is to start in Uganda early in 1994 in a community where the incidence of HIV has remained static at 2% per annum in the general adult population (over 6% in young women) despite intensive education campaigns . Even when symptoms are present, most patients seek unofficial treatment in Africa . Increasing antimicrobial resistance among sexually transmitted pathogens in Africa makes STD treatment more expensive . The introduction of user charges in Nairobi led to a sudden fall in attendances at the main STD clinic and in other countries in the region . The treatment of the STDs prevents future infections, thus STD treatment should be free with the help of international donors . Planta Med, 1993 Dec, 59(6), 546 - 51 Five new prenylated p-hydroxybenzoic acid derivatives with antimicrobial and molluscicidal activity from Piper aduncum leaves; Orjala J et al.; Five new prenylated benzoic acid derivatives, methyl 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxybenzoate (1), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-hydroxybenzoate (2), 1-(1-methylethyl)-4-methyl-3-cyclohexenyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (3), methyl 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoate (4), and 4-hydroxy-3-(3-methyl-2-butenyl)-5-(3-methyl-2-butenyl)-benzoic acid (5) were isolated from the dried leaves of Piper aduncum L . (Piperaceae) . Together with the new metabolites, four known prenylated benzoic acid derivatives, 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid (6), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid (nervogenic acid, 7), methyl 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoate (8), and methyl 4-hydroxy-3-(3-methyl-2-butenyl)-benzoate (9) as well as, dillapiol (10), myristicin, and the three sesquiterpenes humulene, caryophyllene epoxide, and humulene epoxide were isolated . Compounds 7, 8, and 9 are reported as natural products for the first time . The structures of the isolates were elucidated by spectroscopic methods, mainly 1D-and 2D-NMR spectroscopy . Isolates 4-7, 9, and 10 were molluscicidal while 2, 5-7, and 9 displayed significant antibacterial activities. Planta Med, 1993 Dec, 59(6), 517 - 20 Bioactive compounds from the buds of Platanus orientalis and isolation of a new kaempferol glycoside; Mitrokotsa D et al.; A new compound kaempferol 3-O-alpha-L-(2"-E-p-coumaroyl)-rhamnopyranoside, as well as the known flavonoids, kaempferol 3-O-beta-D-(6"-E-p-coumaroyl)-glucopyranoside, kaempferol 3-O-alpha-L-(2",3"-di-E-p-coumaroyl)-rhamnopyranoside, and caffeic acid were obtained from the methanolic extract of Platanus orientalis L . buds . All the compounds were isolated by column chromatography and identified using 1H-NMR, 2D-1H-NMR (COSY), 1H-13C-NMR, and CIDMS techniques . Cytotoxic and antimicrobial studies were carried out in vitro against human cell lines and against Gram-positive and Gram-negative organisms. Planta Med, 1993 Dec, 59(6), 485 - 90 Abietane acids: sources, biological activities, and therapeutic uses; San Feliciano A et al.; The biological activities of natural abietane acids and their derivatives have been reviewed from 1967 to 1992 . Antimicrobial, antiulcer, and cardiovascular activities are the most representative for this class of diterpenoids, while others like allergenic, antiallergic, filmogenic, surfactant, antifeedant, etc . activities, which determine several uses of abietane acids, have also been reported. Pediatr Infect Dis J, 1993 Dec, 12(12 Suppl 3), S112 - 7 Comparative safety and efficacy of clarithromycin and cefadroxil suspensions in the treatment of mild to moderate skin and skin structure infections in children; Hebert AA et al.; A prospective, randomized, single (investigator) blind multicenter study was performed to compare the safety and efficacy of clarithromycin and cefadroxil oral suspensions in the treatment of mild to moderate skin and skin structure infections in children . Male and female patients ages 6 months to 12 years were enrolled at 24 study centers in the United States . Patients had signs and symptoms consistent with mild to moderate skin or skin structure infections judged suitable for oral antimicrobial therapy . Clarithromycin oral suspension was given to 118 children in a dose of 7.5 mg/kg (maximum of 500 mg) twice daily; cefadroxil oral suspension was given to 113 children in a dose of 15 mg/kg (maximum of 1000 mg) twice daily . Among clinically evaluable patients clinical success rates (cure plus improvement) were 96% (71 of 74) for clarithromycin and 98% (83 of 85) for cefadroxil (P = 0.664) . Bacteriologic cure rates in evaluable clarithromycin and cefadroxil patients were 96% (72 of 75) and 99% (89 of 90), respectively (P = 0.331) . Pathogen eradication rates based on 204 evaluable pathogens were 97% in the clarithromycin group and 99% in the cefadroxil group (P = 0.326) . Adverse events were mild or moderate and were reported in 25% of clarithromycin and 35% of cefadroxil patients (P = 0.085) . In both groups adverse events involved primarily the digestive tract . No significant laboratory changes were noted . Clarithromycin oral suspension appears to be a safe and effective alternative to cefadroxil for the treatment of pediatric skin and skin structure infections. Kansenshogaku Zasshi, 1993 Dec, 67(12), 1211 - 8 {A healthy carrier of verotoxin-producing Escherichia coli, who was detected by periodic feces examinations}; Murata Y et al.; Verotoxin-producing Escherichia coli (VTEC) was rapidly detected by the PCR method in one of the 9 feces samples . They were collected from the people who had been cooking meals for patients on a periodic feces examination on November 25, 1992 . It was confirmed by PCR that the isolate had both VT1 and VT2vh toxic genes and showed cytotoxicity on Verocells . In this case, the isolate was highly susceptible to common antibiotic agents, it was removed by the administration of tosfulaxacin . Some isolates which had the same properties as those of the strain described in "VITEK GNI card" and the antimicrobial susceptibility and VT toxin types, were detected in 2 of the 3 members of her family, they were healthy carriers and did not have any subjective symptoms such as diarrhea or abdominal pain . In order to detect Verotoxic genes, the sample of feces preincubated for 3 h in trypticase broth was subjected to PCR . We recommend that this method is much more useful because of rapid detection and identification of VTEC compared with the classical culture method. J Antibiot (Tokyo), 1993 Dec, 46(12), 1859 - 65 In vitro and ex vivo free radical scavenging activities of carazostatin, carbazomycin B and their derivatives; Kato S et al.; Free radical scavenging activities of various carbazole compounds, carazostatin, carbazomycin B and their chemically modified derivatives were studied in vitro and ex vivo . Among these compounds, carazostatin, which was isolated as a free radical scavenger from the culture of Streptomyces chromofuscus, showed the most potent inhibitory activity against lipid peroxidation of rat brain homogenate in vitro . Carbazomycin B, a known antimicrobial antibiotic, also exhibited strong activity in this system . Although O-modified derivatives of carazostatin and carbazomycin B retained considerable activity, N,O-dimethyl derivatives did not suppress the peroxidation . On the other hand, the results from the ex vivo evaluation of these carbazoles in the lipid peroxidation system of mouse blood plasma showed that the original compounds as well as their O-modified derivatives had a strong inhibitory activity upon oral administration to mice . These findings suggest that these natural carbazoles and their effective derivatives can protect tissues from the peroxidative damage due to generation of free radicals. J Antibiot (Tokyo), 1993 Dec, 46(12), 1834 - 42 Thiomarinol, a new hybrid antimicrobial antibiotic produced by a marine bacterium . Fermentation, isolation, structure, and antimicrobial activity; Shiozawa H et al.; Thiomarinol, an antimicrobial antibiotic, was isolated from the culture broth of a marine bacterium, Alteromonas rava sp . nov . SANK 73390 . Its structure was deduced as a hybrid composed of a pseudomonic acid analogue and holothin by NMR spectral analysis and chemical degradation . Antimicrobial activity against Gram-positive and Gram-negative bacteria of thiomarinol was stronger than both of pseudomonic acids and pyrrothine antibiotics. J Antibiot (Tokyo), 1993 Dec, 46(12), 1799 - 803 A new antitumor substance, BE-18591, produced by a streptomycete . I . Fermentation, isolation, physico-chemical and biological properties; Kojiri K et al.; New antitumor substance, designated BE-18591, was isolated from the culture broth of a streptomycete, strain BA18591 . The active principle was extracted from mycelium by methanol and purified by silica gel chromatography . BE-18591 inhibited the growth of MKN-45 human stomach cancer cell line as well as P388 cell line . In in vivo experiments, BE-18591 inhibited the growth of Ehrlich ascites tumor.BE-18591 showed antimicrobial activity against Gram-positive and some Gram-negative bacteria. Burns, 1993 Dec, 19(6), 529 - 30 Concentration of orally administered antimicrobial agent in burn scar tissue, granulation tissue, normal skin and serum; Sawada Y et al.; Tissue and serum concentrations of orally administered ofloxacin were measured using high performance liquid chromatography . From 56 patients who received 200 mg of ofloxacin prior to surgery, 103 specimens including 48 of serum, 32 of scar tissue, 18 of normal skin and five of granulation tissue were harvested between 2 and 3 h after administration . The ofloxacin values were 1798.6 +/- 1125.5 ng/g in the granulation tissue followed by 1525.5 +/- 1002.7 ng/ml in the serum, 1450.0 +/- 1011.3 ng/g in the scar tissue and 1092.8 +/- 593.3 ng/g in normal skin . There was no statistically significant difference between the ofloxacin concentrations in those four specimens by ANOVA test. J Am Vet Med Assoc, 1993 Dec 1, 203(11), 1576 - 8 Effect of intrauterine antimicrobial treatment in reducing calving-to-conception interval in cows with endometritis; Thurmond MC et al.; A prospective clinical trial was conducted on 2 large dairies in the San Joaquin Valley of California to determine whether a single intrauterine infusion with procaine penicillin G or oxytetracycline reduced the calving-to-conception interval in cows with endometritis . Cows with endometritis were randomly assigned to a treatment or a control group . The uterus of treated cows on 1 dairy was infused with 0.8 to 1.0 million U of procaine penicillin G in 40 ml of sterile water, and the uterus of treated cows on the other dairy was infused with 500 mg of oxytetracycline in 20 ml of sterile water, both of which were typical doses used on dairies in the area . A difference was not observed in the cumulative proportion of cows remaining nonpregnant between 87 penicillin-treated and 77 control cows on the 1 dairy (P = 0.356), or between 74 oxytetracycline-treated and 62 control cows on the other dairy (P = 0.174) . Results suggest that routine infusion of antibiotics to treat endometritis, as commonly practiced, may not be efficacious. Nippon Rinsho, 1993 Dec, 51(12), 3272 - 7 {Eradication therapy of Helicobacter pylori in gastroduodenal ulcer and its long-term course}; Kodama R et al.; We investigated the efficacy of antimicrobial drugs, amoxicillin and clarithromycin that have the in vitro activity against H . pylori, and observed a long term course of ulcer after eradication . The eradication rate of combination therapy with PPI and amoxicillin showed best result (13/18: 72%) . In eradicated cases, index of PAS positive substance and gastritis score in antral mucosa that is histological examination was improved, and ammonia concentration in gastric secretions decreased . The recurrent rate of ulcer in long term course after eradication was investigated, the recurrent rate of ulcer was significantly lower in H pylori eradicated cases than in H . pylori continuously positive cases . Results suggest that eradication of H . pylori may be controlled recurrence of H . pylori positive peptic ulcer. Nippon Rinsho, 1993 Dec, 51(12), 3255 - 60 {In vitro anti-microbial activity against H . pylori and clinical efficacy of various drugs}; Fujioka T et al.; The in vitro antimicrobial activity against H . pylori and clinical efficacy of various antibiotics and antiulcer drugs are summarized in this study . H . pylori highly sensitive to most of the beta-lactams and macrolides . Especially, amoxicillin and clarithromycin have satisfactory in vitro activity against H . pylori . The anti-ulcer drugs, sofalcon and plaunotol, used in Japan as mucosal protective agents, also have a weak activity against H . pylori with MIC50 12.5 micrograms/ml and MIC90, 50-100 micrograms/ml, while H2-receptor antagonists do not have in vitro activity . Efficacy of antibiotics as monotherapy for eradicating H . pylori is rather poor . The best results with monotherapy are obtained with clarithromycin and amoxicillin . Omeprazole monotherapy suppresses H . pylori infection but does not eradicate H . pylori . Combined therapy with omeprazole and amoxicillin have strong synergistic effects on the eradication of H . pylori (68.8%) . Newly developed proton pump inhibitors, such as lansoprazole, E-3810 and their derivatives, showed strong in vitro activity against H . pylori suggesting that these drugs may be useful for the treatment of H . pylori infection. Nippon Rinsho, 1993 Dec, 51(12), 3210 - 4 {Helicobacter pylori and gastroduodenal ulcers}; Nishio A et al.; We studied the prevalence of Helicobacter pylori (H.P.) infection in gastroduodenal diseases . H.P . was positive in 67.6% of gastric ulcer patients and 82.2% of duodenal ulcer patients . H.P . was detected with high frequency throughout the course of ulcer healing . Short-term antimicrobial therapy, including cefixim, ofloxacin and bismuth subnitrate, was effective in 50% of H.P . positive patients . However, H.P . was detected again in a considerable number of patients one year after the treatment . Histological inflammation of the antral mucosa of the stomach was stronger in H.P . positive patients than that in H.P . negative patients . Eradication of H.P . had an improving effect on the inflammation of the stomach, irrespective of the use of concomitant drugs. Am J Surg, 1993 Dec, 166(6), 734 - 7 Randomized, prospective comparison of first- and second-generation cephalosporins as infection prophylaxis for cardiac surgery; Curtis JJ et al.; Surgical wound infections after cardiovascular surgery may be life threatening and are resource intensive . Second-generation cephalosporins are purported to have a broader antimicrobial spectrum than first-generation cephalosporins and, therefore, may be more efficacious for infection prophylaxis . We have conducted a randomized prospective study of 702 patients undergoing open heart surgery to test the hypothesis that the second-generation cephalosporin, cefuroxime, will be more efficacious for infection prophylaxis than the first-generation cephalosporin, cefazolin . Patients were randomized to receive cefazolin 1 g intravenously every 8 hours for 48 hours begun 1 hour preoperatively plus 1 g after 4 hours of surgery (8 doses, n = 425) or cefuroxime 1.5 g 1 hour prior to surgery plus 1.5 g every 12 hours for 3 additional doses (4 doses, n = 277) . Infection was defined as a draining wound with or without a positive culture . There was no difference in the wound infection rate between the groups (p = 0.68) . Chest wound infections occurred in 2.1% of patients treated with cefazolin and 2.9% of patients treated with cefuroxime (p = 0.79) . The rate of true mediastinitis requiring exploration and drainage was 0.7% in both groups (p = 0.084) . Leg infections occurred in 6.6% of cefazolin-treated patients and 5.6% of cefuroxime-treated patients (p = 0.83) . The second-generation cephalosporin, cefuroxime, did not reduce the incidence of wound infection when compared with the first-generation cephalosporin, cefazolin . Since institutional antibiotic acquisition and administration costs vary, careful analysis of these factors will allow determination of the most cost-effective infection prophylaxis regimen in cardiac surgery. Am Rev Respir Dis, 1993 Dec, 148(6 Pt 1), 1558 - 62 Serum type III procollagen peptide in patients with Pneumocystis carinii infection . The Copenhagen-Amsterdam PCP-Prednisolone Study Group; Bentsen KD et al.; Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP) . Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders . To investigate changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive serum samples were taken from 48 HIV-infected patients with PCP in a randomized, placebo-controlled study of the effect of adjunctive methylprednisolone therapy (26 in corticosteroid {CS} group and 22 in control group) . All patients were treated with co-trimoxazole . In the control group, PIIINP serum levels at day of initiation of therapy (Day 0) were significantly higher in patients requiring mechanical ventilation and/or dying during the course of the pneumonia, and serum levels of PIIINP higher than 5 ng/ml were associated with a higher mortality than levels below 5 ng/ml . The level of PIIINP increased from Day 0 to Day 5 . There was a significant correlation between changes in PIIINP levels and changes in the alveolar-arterial oxygen gradient from Day 0 to Day 5 . In the CS group, the PIIINP levels decreased while steroid was administered . At Days 21 to 28 there were no difference in the levels of PIIINP between the two groups . PIIINP serum levels may predict the clinical outcome of PCP . The antimicrobial therapy may exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory failure . CS prevents this increased inflammatory activity. Am Rev Respir Dis, 1993 Dec, 148(6 Pt 1), 1541 - 6 Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice; Ji B et al.; To identify alternative regimens for preventive therapy of tuberculosis, the pharmacokinetics and antimicrobial activities of rifampin (RMP), rifabutin (RBT), and rifapentine (RPT) were compared in BCG-vaccinated and M . tuberculosis-infected immunocompetent mice . RPT showed the highest serum peak level (Cmax) and the longest half-life (t1/2), whereas RBT displayed the lowest Cmax and the shortest t1/2 . On weight-to-weight basis, both RPT and RBT were more bactericidal than RMP . The activity of RMP was significantly reduced when the frequency of administration was reduced from six to three times weekly, whereas significant bactericidal activity was still observed in mice treated with RPT, 10 mg/kg up to once fortnightly, or RBT, 10 mg/kg twice weekly . Because the bactericidal activity of RBT, 10 mg/kg six times/wk for 6 wk, or RPT, 10 mg/kg two times/wk for 12 wk, was comparable to that of RMP, 10 mg/kg six times/wk for 12 wk in mice, the two regimens are appropriate for clinical trials of preventive therapy of tuberculosis. Clin Orthop, 1993 Dec, (297), 95 - 9 Nonspecific diskitis in children . A nonmicrobial disease? Ryoppy S, Jaaskelainen J, Rapola J, Alberty A. Eighteen patients were treated for nonspecific diskitis (diskitis without microbial cause) at the University Children's Hospital in Helsinki during 1970-1990 . The mean age at admission was three years three months . The characteristic findings were restriction of spinal mobility and an elevated erythrocyte sedimentation rate (ESR) . Radiographic narrowing of the affected disk space was seen four to five weeks after the initial symptoms . An operative biopsy was made in 16 patients, the histologic diagnosis being chronic or subacute nonspecific inflammation in ten, other nonspecific changes in two, and normal tissue in five . Treatment was either bed rest and antimicrobial medication, or bed rest alone . After a follow-up period of five months to nine years, all patients were clinically normal . All but two had radiographic signs of healed disk space defects . Nonspecific diskitis in children is an entity with unknown cause . The clinical picture is typical, but diagnostic difficulties may be encountered during the first weeks when radiographic signs are absent . The disease is self-limiting in most cases, and only minor radiographic changes remain after healing . The results after routine operative biopsy raise the question of a possible nonmicrobial cause. EMBO J, 1993 Dec, 12(12), 4829 - 32 Antibacterial and haemolytic peptides containing D-alloisoleucine from the skin of Bombina variegata; Mignogna G et al.; A family of bombinin-related peptides is present in the skin of Bombina variegata . These peptides contain 27 residues with Gly as N-terminus and display antimicrobial activity . From sequence analysis of the cDNAs encoding for the corresponding peptide precursors, the presence of a novel 20-residue peptide with Ile as N-terminus was predicted . We have now purified a family of hydrophobic peptides named H1-H5, whose sequences correspond to the predicted peptide with some variability in positions 1, 2 and 8 . In particular, H3-H5 contain a D-alloisoleucine residue in the second position . All these peptides display antibacterial and haemolytic activity. J Chemother, 1993 Dec, 5(6), 499 - 501 In vitro effects of brodimoprim on human polymorphonuclear leukocyte functions . Preliminary results; Mini E et al.; The in vitro effects of brodimoprim and trimethoprim on the functions of human polymorphonuclear (PMN) leukocytes have been studied comparatively evaluating chemotaxis, phagocytosis and production of superoxide anion . No significant effects of both diaminopyrimidines on chemotaxis and phagocytic activity of PMNs have been observed while both brodimoprim and trimethoprim enhanced the oxidative burst . A synergistic activity between the host immune system and the direct antimicrobial action of brodimoprim may occur while using this diaminopyrimidine in vivo. J Chemother, 1993 Dec, 5(6), 361 - 8 History and future of antimicrobial diaminopyrimidines; Then RL; Numerous pyrimidine and purine analogs were synthesized in the late forties in G.H . Hitchings' group as potential nucleic acid antagonists . Several key observations finally led to the selection of pyrimethamine as an antimalarial and trimethoprim (TMP) as an antibacterial agent: i) 2,4-diamino-5-substituted pyrimidines interfered with folic acid utilization rather than being thymine antagonists as expected; ii) a large degree of selectivity could be obtained by suitable substitution and non-toxic diaminopyrimidines with preferential antimicrobial activity were found; iii) the identification of dihydrofolate reductase (DHFR) as the specific target for aminopterin and methotrexate in 1958 and for TMP in 1965, and the diversity of this enzyme in different species . Although several diaminopyrimidines were initially tested as monotherapies in clinical trials, the pronounced synergism between some of these new compounds and sulfonamides seen against Plasmodium was finally also applied in the development of TMP . Its combination with sulfamethoxazole later proved one of the most successful agents ever developed . Further milestones in the application of antimicrobial DHFR inhibitors were the introduction of TMP alone in 1972, the launch of a new combination of tetroxoprim, a close TMP-analog, with sulfadiazine, and the successful clinical trials with brodimoprim, which proved clinically efficacious and safe with once-daily low dose monotherapy . Efforts to discover new antimicrobial DHFR inhibitors have recently intensified . DHFRs from important gram-positive problem organisms such as S . aureus, S . epidermidis have been cloned and sequenced, as well as DHFRs from opportunistic pathogens such as P . carinii, T . gondii, and of mycobacteria . DHFR crystal structures from several of these organisms are available to aid rational inhibitor design.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Clin Microbiol Infect Dis, 1993 Dec, 12(12), 944 - 7 Effect of antimicrobial and antineoplastic drugs on the uptake of fluconazole by human neutrophils and tissue culture cells; Garcia I et al.; The effect of eight antimicrobial and three antineoplastic drugs on the uptake of fluconazole by human neutrophils and culture epithelial cells was evaluated . Fluconazole reached higher concentrations intracellularly than extracellularly (cellular to extracellular concentration ratio C/E > or = 1.3) in the presence of therapeutical concentrations of the antimicrobial and antineoplastic agents evaluated. J Ethnopharmacol, 1993 Dec, 40(3), 181 - 6 Antibacterial, antifungal and anthelmintic activities of root barks of Uvaria hookeri and Uvaria narum; Padmaja V et al.; On a pharmacological screening, substantial antibacterial, antifungal and anthelmintic activities were observed for the hexane and ethyl acetate extracts of the root barks of Uvaria narum Wall . and Uvaria hookeri King . Chromatographic fractionation of these extracts led to the isolation of the triterpenes glutinol, glutinone, taraxerol, beta-sitosterol and Annonaceous acetogenins uvariamicins-I, II and III mixture, isodesacetyluvaricin, squamocin-28-one, narumicins-I and II stereoisomeric mixture, squamocin and panalicin . The acetogenins exhibited antimicrobial and anthelmintic activities in their individual screening comparable with standard drugs and hence their presence could be attributed to a great extent for the biocidal properties of U . narum and U . hookeri extracts. Forensic Sci Int, 1993 Dec, 63(1-3), 261 - 8 Utilization of hair analysis for therapeutic drug monitoring with a special reference to ofloxacin and to nicotine; Uematsu T; Human scalp hair retains the past dosage history over a rather long period of time, acting as 'tape-recorder' . Each 1-cm length of hair contains the drug approximately corresponding to the amount ingested over a 1-month period when the hair is cut into 1-cm lengths successively from the scalp end . However, the hair growth rate is variable both within and between subjects and the hair has its own growth cycle . Therefore, the validity of obtained results must always be considered cautiously, especially in relation to whether resting-stage hair might have been sampled . It has been found that antimicrobial quinolones are detectable in hair, even after a short exposure to them, and serve as time marker for estimating the growth rate itself and the stage of hair . By analysing the axial distribution of ofloxacin-one of the most frequently prescribed quinolone derivatives in Japan-along the hair shaft, the 'tape-speed' and 'uniformity of tape-running' of a single hair can be estimated . Research into cigarette-smoking behavior necessitates accurate measurement of smoking habit . It has been found that the nicotine content in hair is proportional to the number of cigarettes consumed daily . Moreover, the cm-by-cm analysis of axial nicotine distribution along the hair shafts revealed the concentrations of nicotine approximately proportional to the month-by-month self-report on daily-consumed cigarettes in a subject who participated in a smoking-cessation program. Braz J Med Biol Res, 1993 Dec, 26(12), 1279 - 89 Histology of the mucosa of gastric antrum and body before and after eradication of Helicobacter pylori; Resende LM et al.; 1 . Helicobacter pylori status and the histology of the antral and oxyntic mucosa were evaluated in 25 patients with duodenal ulcer treated with a triple schedule of furazolidone, metronidazole and amoxicillin, and in 16 patients treated only with cimetidine . 2 . Before treatment, H . pylori was detected in all patients . One month after treatment with the antimicrobial agents, H . pylori was not found in 18 (72.0%) of 25 patients treated with the triple schedule . In the patients treated with cimetidine (N = 16) the H . pylori tests continued to be positive after treatment . 3 . Inflammatory activity and intensity of gastritis were significantly reduced in patients treated with the antimicrobial agents but not in cimetidine-treated patients . Three patients who had negative cultures and improvement of gastritis 1 month after treatment became H . pylori positive again within 2 months, with concomitant reappearance of gastritis . 4 . This study provides additional evidence that histological gastritis observed in H . pylori-positive patients with duodenal ulcer is due to the presence of the microorganism. Farmaco, 1993 Dec, 48(12), 1725 - 33 Synthesis and antifungal activity of pyrido{3',2':4,5}thieno{3,2-d}- 1,2,3-triazine derivatives; Guerrera F et al.; The antimicrobial activity of some pyrido{3',2':4,5}thieno{3,2-d}- 1,2,3-triazine derivatives has been studied . Some compounds proved effective against microorganisms in vitro, compounds 3a and 3c in particular exhibited antifungal activity, comparable to MCZ, against hyphomycetes. J Nat Prod, 1993 Dec, 56(12), 2041 - 5 Two new sesquiterpene lactones from Ceiba pentandra; Rao KV et al.; Two new sesquiterpene lactones showing moderate antimicrobial activity have been isolated from the root bark of Ceiba pentandra (Bombacaceae) in addition to the known compounds 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthaquinone+ ++ {1}, and 7-hydroxycadalene {2} . The new compounds were characterized as 2,7-dimethoxy-5-isopropyl-3-methyl-8,1-naphthalene carbolactone {3} and 2-hydroxy-5-isopropyl-7-methoxy-3-methyl-8,1-naphthalene carbolactone {4} by chemical and spectroscopic studies. J Dairy Sci, 1993 Dec, 76(12), 3851 - 63 Lipid metabolism in the rumen; Jenkins TC; Recent advances in ruminal lipid metabolism have focused primarily on manipulation of physicochemical events in the rumen aimed at two practical outcomes: 1) control of antimicrobial effects of fatty acids so that additional fat can be fed to ruminants without disruption of ruminal fermentation and digestion and 2) regulation of microbial biohydrogenation to alter the absorption of selected fatty acids that might enhance performance or reduce saturation of meat and milk . Properties of lipids that determine their antimicrobial effects in the rumen include type of functional group, degree of unsaturation, formation of carboxylate salts, and physical association of lipids with surfaces of feed particles and microbes . The mechanism of how lipids interfere with ruminal fermentation is a complex model involving partitioning of lipid into the microbial cell membrane, potency of the lipid to disrupt membrane and cellular function, physical attachment of microbial cells to plant surfaces, and expression and activity of microbial hydrolytic enzymes . Lipolytic and hydrogenation rates vary with forage quality (stage of maturity and N content), surface area of feed particles in the rumen, and structural modifications of the lipid molecule that inhibit attack by bacterial isomerases. J Dairy Sci, 1993 Dec, 76(12), 3812 - 31 Bovine mammary lactoferrin: implications from messenger ribonucleic acid (mRNA) sequence and regulation contrary to other milk proteins; Schanbacher FL et al.; The regulation of bovine mammary lactoferrin, an important component of the antimicrobial defenses of the mammary gland, is poorly understood compared with the other milk proteins . The complete sequence for bovine lactoferrin mRNA shows it to be highly homologous to other lactoferrins and transferrins . However, regional differences in the deduced AA sequence of bovine lactoferrin compared with human lactoferrin and transferrin imply functional differences between them . Steady-state levels of bovine lactoferrin mRNA (by Northern blot) in the bovine mammary gland indicate that bovine lactoferrin expression is minimal in the developing and lactating gland but is strongly induced by mammary involution . The overall regulation of bovine lactoferrin in the mammary gland appears to be contrary to that of the other milk proteins . Features identified in the mRNA of bovine mammary lactoferrin may contribute to the differences in regulation between lactoferrin and other bovine milk proteins and to differences in concentrations of lactoferrin in milk across species . Lactoferrin secretion by bovine mammary cells grown in vitro does not appear to be dependent on prolactin and shows regulation by substratum, serum, and cell population to be different from that for casein . In contrast to casein, efficient secretion of lactoferrin from the cell does not require detachment of collagen substratum. Eur Heart J, 1993 Dec, 14 Suppl K, 20 - 3 Thrombo-embolic complications in bacteraemic infections; Valtonen V et al.; Thrombo-embolic complications including stroke and myocardial infarction are common in bacteraemic patients with and without endocarditis: about 20% of patients with infective endocarditis will develop stroke during their disease . Small miliary type myocardial infarctions are found in about 80-90% of autopsied endocarditis patients, but large myocardial infarctions are much more infrequent and acute myocardial infarctions are seldom diagnosed in the lifetime of these patients . About 10% of bacteraemic patients without endocarditis will develop stroke within one month of the onset of bacteraemia, and about 4% of bacteraemic patients will develop myocardial infarction . The risk of cerebral or myocardial infarction is very high in bacteraemic patients compared with the corresponding risk in the general population of the same age, and it has been estimated that about 10% of all strokes are associated with bacteraemic infections . The mechanisms which could cause thrombo-embolic complications in septic patients are numerous, but activation of the coagulation system is probably the most important . Currently, appropriate antimicrobial therapy is the best way to reduce mortality and also probably thrombo-embolic complications in bacteraemic patients who are not routinely using any anticoagulant therapy. Contraception, 1993 Dec, 48(6), 591 - 6 Studies on the contraceptive efficacy of Praneem polyherbal cream; Garg S et al.; Praneem polyherbal cream, a spermicidal formulation, has been developed at the National Institute of Immunology, which makes use of Praneem, a purified extract from the dried seeds of an ancient Indian plant Azadirachta indica (Neem), extract from the pericarp of fruits of Sapindus species and quinine hydrochloride . These ingredients have a synergistic spermicidal activity and an optimised formula was derived . The components were made into a water-soluble cream base prepared by using pharmaceutically acceptable base and stabilised by addition of IP grade antioxidant and preservatives . The cream is devoid of irritation and sensitization potential, as seen with standard Draize test on normal and abraded skin of rabbits and by 21-day cumulative skin sensitivity in human volunteers . The formulation was found to be safe under subacute toxicity studies in monkeys . The formulation has shown high contraceptive efficacy in rabbits and in monkeys after intravaginal application . The shelf-life of the cream at room temperature is estimated to be 18 months by accelerated stability studiesPIP: In India, the National Institute of Immunology has developed Praneem polyherbal cream as a vaginal spermicide . Scientists combined a purified extract from the dried seeds of an ancient Indian plant Azadirachta indica (Neem), extract from the pericarp of fruits of Sapindus species, and quinine hydrochloride with a pharmaceutically acceptable base to make a water-soluble cream base . They added IP grade antioxidant and preservatives to stabilize the cream base . They applied the cream on a shaved or abraded part of the skin of human volunteers and rabbits and inserted it into the vagina of Bonnet monkeys to test for sensitivity and irritation . They studied the dissolution characteristics of the cream after intravaginal application in the rabbits and monkeys . They compared pregnancy rates of monkeys who received intravaginal application of 2 ml cream every day with those of control monkeys . Praneem polyherbal cream did not irritate the skin of the rabbits or the human volunteers . The accelerated stability studies found the shelf-life of the cream at room temperature to be 18 months . The cream dissolves entirely within 30 minutes in the vaginal secretions of the rabbits and 40 minutes in those of the monkeys . Precoital application of the cream provided complete protection against pregnancy in rabbits in the 1st 30 minutes after application . The conception rate was acceptable at 60 minutes (7%), but thereafter it climbed to unacceptable levels (28.6% at 90 minutes and 75% at 12 hours) . The conception rate of monkeys who received precoital application of Praneem polyherbal cream was only 2.27% . These results suggest that Praneem polyherbal cream can protect against pregnancy without causing irritation . Its antimicrobial properties provide another advantage . Biomaterials, 1993 Dec, 14(15), 1135 - 9 Human neutrophil chemokinesis and polarization induced by hyaluronic acid derivatives; Campoccia D et al.; Neutrophils and macrophages are known to undergo significant modifications in their morphology and basal metabolism in response to chemical factors, in particular changes in the shape, movement, phagocytic activity and degranulation . These phenomena often involve an increase in chemokinesis and cellular secretory activity, usually expressed in antimicrobial activity . Once activated, the cells can move quickly towards the source of the stimulus, where they produce and release great amounts of enzymes (e.g . proteases, hydrolases, lysozyme) and reactive oxygen metabolites (e.g . O2-., H2O2, OH.) . This study has examined the ability of surfaces of selected biomaterials to influence neutrophil morphology and locomotion . The surface of two films derived from hyaluronic acid derivatives were compared with that of glass . The two hyaluronic acid derivatives, despite having a similar chemical structure, were shown to interact with human neutrophils in different ways . A hyaluronic acid ethyl ester stimulated the whole population of neutrophils to take up a non-spherical morphology (polarize) and to move with a velocity similar to that of N-formyl-methionine-leucine-phenylalanine-stimulated cells on a glass surface . In contrast, only 44% of the examined cells on the surface of hyaluronic acid benzyl ester were polarized and their mean speed was only slightly higher with respect to that found with non-stimulated cells on glass . Moreover, while on the benzyl ester and on glass a correlation between neutrophil circularity (i.e . the shape of the cell) and cell speed was found, the ethyl ester did not show any correlation. Ann Pediatr (Paris), 1993 Dec, 40(10), 622 - 4 {Fulminant pneumococcal septicemia in a splenectomized child despite vaccination and chemoprophylaxis: necessity for education of the entourage}; Sizun J et al.; A splenectomized three-year-old developed fulminant pneumococcal septicemia despite immunization and chemoprophylaxis . The course was rapidly fatal . Fulminant pneumococcal septicemia mainly affects splenectomized individuals and is associated with very substantial mortality . Immunization prior to splenectomy and daily prophylactic oral penicillin have partial preventive efficacy . Other useful measures include carrying a health status card and inpatient antimicrobial therapy in the event of fever . The need for these precautions should be repeatedly discussed with the child's parents and physician. J Vet Pharmacol Ther, 1993 Dec, 16(4), 462 - 8 Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs; Kung K et al.; Four dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross-over study . Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method . Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature . Mean enrofloxacin t1/2 lambda z was 2.4 h, mean Cls was 27.1 ml/min.kg, and mean Vss was 7.0 l/kg . After i.v . and p.o . administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (Cmax = 0.2 microgram/ml, tmax = 2.2 h after intravenous administration; Cmax = 0.2 microgram/ml, tmax = 3.6 h after oral administration) . A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrofloxacin. Clin Pharmacokinet, 1993 Dec, 25(6), 450 - 82 Pharmacokinetic drug interactions with antimicrobial agents; Gillum JG et al.; As new classes of antimicrobial drugs have become available, and new uses found for older drugs, pharmacokinetic drug interactions with antimicrobials have become more common . Macrolides, fluoroquinolones, rifamycins, azoles and other agents can interact adversely with commonly used drugs, usually by altering their hepatic metabolism . The mechanisms by which antimicrobial agents alter the biotransformation of other drugs is increasingly understood to reflect inhibition or induction of specific cytochrome P450 enzymes . Macrolides inhibit cytochrome P450IIIA4 (CYP3A4), which appears to be the most common metabolic enzyme in the human liver and is involved in the metabolism of many drugs, including cyclosporin, warfarin and terfenadine . Some quinolones preferentially inhibit CYP1A2, which is partially responsible for methylxanthine metabolism . Azoles appear to be broad spectrum inhibitors of cytochromes P450 . Within each of these antibiotic classes, there is a rank order of inhibitory potency towards specific cytochrome P450 enzymes . By contrast, rifampicin (rifampin) and rifabutin induce several cytochromes P450, including CYP3A4, and hence can enhance the metabolism of many other drugs . By using in vitro preparations of human enzymes it is increasingly possible to predict those antibiotics that will adversely affect the metabolism of other drugs . In addition, between-patient variability in frequency of interaction may relate to differences in the activities of these enzymes . Although the mechanisms and scope of these interactions are becoming well characterised, the remaining challenge is how to best inform the clinician so that the undesirable consequences of interactions may be prevented. Clin Infect Dis, 1993 Dec, 17(6), 976 - 80 Tularemia: treatment failures with outpatient use of ceftriaxone; Cross JT et al.; Tularemia, an infection caused by the coccobacillus Francisella tularensis, can be a difficult disease process to diagnose and treat . The difficulty in treating this disease is related to the pathophysiology of the infection and the toxicity of the antimicrobial agents presently recommended for treatment . Recent in vitro data have suggested that antimicrobial drugs other than standard agents (streptomycin, gentamicin, chloramphenicol, or tetracycline) may be effective . We present eight cases of documented failure of outpatient use of ceftriaxone in the treatment of tularemia . Our data suggest that while ceftriaxone may have excellent MICs in vitro, these MICs do not necessarily correlate with successful in vivo outcomes. Clin Infect Dis, 1993 Dec, 17(6), 1047 - 54 A decade of experience with selective decontamination of the digestive tract as prophylaxis for infections in patients in the intensive care unit: what have we learned? Verhoef J, Verhage EA, Visser MR. Infection is a frequent and often life-threatening complication in patients treated in intensive care units . Many regimens have been developed to prevent infections in these patients . Recently, a new method of prophylaxis was introduced: selective decontamination of the digestive tract . This paper reviews the results of studies on selective decontamination of the digestive tract with oral, nonabsorbable antimicrobial agents . Most studies showed a positive effect of selective decontamination; a significant decrease in the incidence of nosocomial pneumonia among patients receiving agents for selective decontamination was observed . However, the great differences among the various studies in the incidence of infections among control patients make it difficult to compare the results . The use of antimicrobial agents for selective decontamination had no effect on mortality and in some studies even led to the emergence of resistant microorganisms . The lack of recent data on the incidence, pathogenesis, and epidemiology of infections in patients in intensive care units makes it difficult to recommend routine use of selective decontamination for these patients. Antimicrob Agents Chemother, 1993 Dec, 37(12), 2733 - 5 Antimicrobial susceptibilities of Gardnerella vaginalis; Kharsany AB et al.; The in vitro susceptibilities of 93 clinical isolates of Gardnerella vaginalis to 25 antimicrobial agents were determined by the agar dilution method . All isolates were susceptible to penicillin, ampicillin, erythromycin, clindamycin, chloramphenicol, and trimethoprim . Activity was poor for vancomycin, LY146032, the cephalosporins, ciprofloxacin, and imipenem . Some resistance was observed with tetracycline and minocycline . The MICs of metronidazole paralleled those of tinidazole, with the hydroxymetabolite of metronidazole being the most active . One strain was resistant to all three agents . Marked resistance to aztreonam, amikacin, and sulfamethoxazole was observed. Antimicrob Agents Chemother, 1993 Dec, 37(12), 2710 - 5 Bactericidal activities of synthetic human leukocyte cathepsin G-derived antibiotic peptides and congeners against Actinobacillus actinomycetemcomitans and Capnocytophaga sputigena; Miyasaki KT et al.; Actinobacillus actinomycetemcomitans and Capnocytophaga spp . are gram-negative bacteria implicated in the etiology of periodontal disease (particularly in individuals with neutrophil defects) and life-threatening systemic infections . They are resistant to many antibiotics of microbial origin but are sensitive to the nonoxidative microbicidal action of neutrophils . These organisms are susceptible to the microbicidal effect of cathepsin G but are killed by two distinct mechanisms . The purpose of this study was to assess their sensitivity to the antibiotic effects of IIGGR and HPQYNQR, antimicrobial peptides derived from human neutrophil cathepsin G . The efficacies of the synthetic peptides IIGGR and HPQYNQR were tested by single-dose screening, dose-response, and kinetic assays against three representative strains (each) of A . actinomycetemcomitans and Capnocytophaga spp . and one strain of Eikenella corrodens . Strains of A . actinomycetemcomitans were sensitive to IIGGR and HPQYNQR at equal concentrations (wt/vol), whereas strains of Capnocytophaga and E . corrodens were more sensitive to IIGGR than to HPQYNQR . These differential antibiotic effects occurred over both time and dose ranges too narrow to be of therapeutic significance but are consistent with the premise that cathepsin G kills these oral bacteria by two distinct mechanisms . Except for IVGGR, congeners of IIGGR, including AIGGR, IAGGR, IIAGR, IIGAR, IIGGA, IQGGR, ILGGR, and I-norleucyl-GGR (InLGGR), were microbicidal at 500 micrograms/ml . IIGGR-amide exhibited no antibiotic activity . The D-enantiomer of IIGGR, DIDIGGDR, was as potent as IIGGR itself . APQYNQR exhibited antibiotic activity but somewhat less than HPQYNQR . We conclude that charge distribution, but not chirality or net charge, is an important determinant in the antibiotic efficacy of IIGGR . Moreover, peptide antibiotics derived from cathepsin G may have therapeutic value against periodontal gram-negative, facultative bacteria. Antimicrob Agents Chemother, 1993 Dec, 37(12), 2584 - 7 In vitro activities of free and liposomal drugs against Mycobacterium avium-M . intracellulare complex and M . tuberculosis; Mehta RT et al.; We compared MICs and MBCs of various free- and liposome-incorporated antimicrobial agents against several patient isolates of Mycobacterium avium-M . intracellulare complex and certain American Type Culture Collection strains of M . avium, M . intracellulare, and Mycobacterium tuberculosis . Seven of 19 agents were selected for incorporation into liposomes . The MICs of these agents for 50 and 90% of isolates tested (MIC50s and MIC90s, respectively) ranged from 0.5 to 62 micrograms/ml . Members of the M . avium-M . intracellulare complex were resistant to killing by most of the other agents tested in the free form . However, clofazimine, resorcinomycin A, and PD 117558 showed complete killing of bacteria at concentrations ranging from 8 to 31 micrograms/ml, represented as MBC90s . Among the liposome-incorporated agents, clofazimine and resorcinomycin A had the highest killing effects (MBC90s, 8 and 16 micrograms/ml, respectively) . Furthermore, both free and liposome-incorporated clofazimine had equivalent growth-inhibitory and killing effects on all American Type Culture Collection strains of M . avium, M . intracellulare, and M . tuberculosis tested . These results show that the antibacterial activities of certain drugs, particularly those of clofazimine and resorcinomycin, were maintained after the drugs were incorporated into liposomes. J Periodontol, 1993 Dec, 64(12), 1219 - 24 The influence of doxycycline of the attachment of fibroblasts to gelatin-coated surfaces and its cytotoxicity; Tsukuda N et al.; Because of their antimicrobial and anti-inflammatory properties, tetracyclines have been used systemically and locally in the treatment of periodontal disease . This study was done to evaluate the influence of doxycycline (Dc), a tetracycline, on fibroblast adherence to a protein coated surface and its cytotoxicity . Periodontal ligament derived fibroblasts (PLDFs) were either: 1) preincubated with Dc (0 to 100 micrograms/ml) and then allowed to adhere to a gelatin-coated surface or 2) adherence was first established and then Dc added to the system . After an appropriate time the number of PLDFs adherent, released, or lysed was estimated by a lactic dehydrogenase (LDH) assay . Preincubation of PLDFs in 25 micrograms Dc/ml or higher concentrations significantly (P < 0.01) reduced the number of adherent cells . Fifty micrograms Dc/ml and higher doses significantly (P < 0.01) increased PLDFs cytotoxicity as measured by LDH release . The same trend was noted if PLDFs were allowed to adhere and then subjected to the drug . Microscopic observation of fluorescein diacetate/propidium iodide-stained cells showed that attached-spread cells pulled in, rounded up, and detached in proportion to the increased dose of Dc and the percentage of red-stained cytotoxic cells rose in a similar manner . The data suggested that Dc can be cytotoxic and may inhibit PLDFs adherence and spread along a substratum. Infect Dis Clin North Am, 1993 Dec, 7(4), 877 - 98 Echocardiographic detection of cardiac valve vegetations and prognostic implications; Mugge A; Echocardiography is a well-established method for diagnosis of vegetations in patients with infective endocarditis . The sensitivity for detection of valvular vegetations depends on the technique used (M-mode, 2D) and is highest for the transesophageal approach (above 90%) . Transesophageal echocardiography has been very helpful in patients with suspected endocarditis but a negative transthoracic echocardiogram, and in patients with suspected pulmonary and prosthetic valve endocarditis . Specificity of echocardiography is relatively low in unselected patients, but echocardiography has a high diagnostic yield in preselected patients with clinically suspected active endocarditis . Besides the visualization of vegetations, echocardiography (including Doppler) is the method of choice in the diagnosis of endocarditis-associated complications, e.g., valvular destruction with subsequent severe regurgitation, secondary "jet" or "kissing" lesions, and paravalvular abscesses . The diagnostic power of echocardiography in the detection of paravalvular abscesses and abscess-related complications has been substantially improved with the transesophageal approach . In addition, echocardiographic findings may have prognostic implications . The size and mobility of vegetations stratifies endocarditis patients into a high-risk group for arterial embolism . Furthermore, increase in size of vegetations during antimicrobial treatment may identify patients with no, or at least a prolonged, healing process . Thus, echocardiography has an important diagnostic and prognostic impact in patients with infective endocarditis and is today an established adjacent technique to clinical findings and blood cultures. Antibiot Khimioter, 1993 Dec, 38(12), 29 - 34 {Thienam (imipenem/cilastatin) as an agent for empirical antibiotic therapy}; Savitskaia KI et al.; The clinicobacteriological efficacy and tolerance of thienam (imipenem/cylastatin) were studied in the empirical therapy of 38 patients with severe purulent inflammatory diseases of various localization i.e . pneumonia, lung abscesses, pyothorax, peritonitis, abdominal abscesses, meningitis and brain abscesses . The treatment of all the patients with the drug was started before the data on the bacteriological investigation were available . Although the infections and the general state of the patients were extremely severe, the therapy with thienam proved to be efficient in 31 out of 35 cases (88.6 per cent) subjected to the drug efficacy estimation . The bacteriological diagnoses with respect to 24 out of 38 patients (64.7 per cent) were available later: 93.6 per cent of the isolates was sensitive to imipenem . The antimicrobial activity of imipenem against 254 clinical isolates assayed by the method of serial dilutions exceeded that of the majority of the currently used antimicrobial drugs, including aminoglycosides, 3rd generation cephalosporins and ureldopenicillins . The tolerance of thienam was good . Only in 4 out of 38 patients it was necessary to use some other drugs because of the side effects . Therefore, the use of the thienam is advisable as a drug of empirical monotherapy in patients with severe infections of the respiratory organs, abdominal cavity and central nervous system. Gastroenterologist, 1993 Dec, 1(4), 291 - 5 Helicobacter pylori: practical guidelines for diagnosis and treatment; Peura DA; Ulcer disease can be cured in most patients . The discovery of an infectious cause of peptic disease has necessitated new diagnostic and treatment strategies for common upper gastrointestinal tract problems . Appropriate use of one of the many new tests to diagnose Helicobacter pylori can identify those individuals likely to benefit from antimicrobial treatment . Further refinement of antimicrobial regimens should ensure better patient compliance and maximize effective bacterial eradication . H . pylori eradication has been shown to favorably alter the rate of ulcer recurrence and to possibly reduce the risk of subsequent ulcer complications . This review is intended to provide clinicians with practical guidelines for the diagnosis and treatment of H . pylori infection. Biochemistry, 1993 Nov 16, 32(45), 11963 - 8 Structural evidence for a pH-sensitive dilysine trigger in the hen ovotransferrin N-lobe: implications for transferrin iron release; Dewan JC et al.; Members of the transferrin family of proteins are involved in Fe3+ transport (serum transferrins) and are also believed to possess antimicrobial activity (ovotransferrins and lactoferrins) . The structure of the monoferric N-terminal half-molecule of hen ovotransferrin, reported here at 2.3-A resolution, reveals an unusual interdomain interaction formed between the side-chain NZ atoms of Lys 209 and Lys 301, which are 2.3 A apart . This strong interaction appears to be an example of a low-barrier hydrogen bond between the two lysine NZ atoms, both of which are also involved in a hydrogen-bonding interaction with the aromatic ring of a tyrosine residue . Crystals of the protein were grown at pH 5.9, which is well below the usual pKa approximately 10 for a lysine side chain . We suggest that the pKa of either one or both of these residues lies below the pH of the structure determination and is, therefore, not positively charged . This finding may serve to explain, on a molecular basis, the pH dependence of transferrin Fe3+ release . We propose that uptake of the Fe(3+)-transferrin complex into an acidic endosome (viz., pH approximately 5.0) via receptor-mediated endocytosis will result in the protonation of both lysine residues . The close proximity of the two resulting positive charges, and their location on opposite domains of the N-lobe, might well be the driving force that opens the two domains of the protein, exposing the Fe3+ ion and facilitating its release.(ABSTRACT TRUNCATED AT 250 WORDS) J Am Vet Med Assoc, 1993 Nov 15, 203(10), 1445 - 7 Surgical treatment of egg retention in emus; Honnas CM et al.; We developed a surgical technique for management of retained eggs in emus . Clinical signs associated with egg retention include cessation of laying activity or failure to lay eggs, lethargy, anorexia, straining, and passing egg material, and diagnosis can be made by external palpation, abdominal radiography, and ultrasonography . The retained eggs were removed through a paramedian abdominal incision in all birds . One bird was euthanatized at surgery because of severe peritonitis resulting from uterine rupture at the site of obstruction by the retained egg . Three birds survived and were discharged from the hospital to the owners . Egg peritonitis resulting from eggs or egg remnants in the abdominal cavity was evident in the birds that survived surgery . Surgery and administration of antimicrobials were successful in resolving the peritonitis. Biochem Biophys Res Commun, 1993 Nov 15, 196(3), 1363 - 8 A novel cDNA sequence encoding a pig leukocyte antimicrobial peptide with a cathelin-like pro-sequence; Storici P et al.; It has recently been shown that the precursors of various structurally unrelated leukocyte antimicrobial peptides share similar pro-regions . These, in turn, are highly identical to a cysteine proteinase inhibitor named cathelin, or PLCPI . In this paper we report a novel cDNA sequence of porcine bone marrow origin, encoding a protein characterized by a cathelin-like domain . The putative protein is 147 amino acid residue long, with a calculated mass of 16479 Da and appears to be the precursor of a recently isolated antimicrobial peptide named protegrin PG-2 . The unique sequence of the mature PG-2 is located at the C-terminus of the precursor . Similar to the previously reported precursors, both the signal peptide and the pro-sequence of pre-proPG-2 appear highly conserved. Biochem Biophys Res Commun, 1993 Nov 15, 196(3), 1058 - 65 A cDNA derived from pig bone marrow cells predicts a sequence identical to the intestinal antibacterial peptide PR-39; Storici P et al.; We have recently shown that a group of antimicrobial peptides of bovine neutrophils share highly identical pro-sequences . In this paper we report the cDNA sequence of a 172 amino acid residue pig myeloid protein showing a similar pro-sequence of 101 residues . The carboxyl-moiety of the predicted protein is identical to the mature form of the proline- and arginine-rich antibacterial peptide named PR-39, isolated from pig intestine. CMAJ, 1993 Nov 15, 149(10), 1409 - 22 Periodic health examination, 1993 update: 3 . Periodontal diseases: classification, diagnosis, risk factors and prevention . Canadian Task Force on the Periodic Health Examination; Ismail AI et al.; OBJECTIVE: To review the 1979 Canadian Task Force on the Periodic Health Examination recommendations on the diagnosis and prevention of periodontal disease . OPTIONS: Self-care at home, professional care, treatment with antimicrobial agents and management of patients at high risk . OUTCOMES: Maintaining the gingiva, alveolar bone and periodontal ligament in a healthy state (absence of gingival bleeding and no loss of epithelial attachment) . EVIDENCE: A literature search for articles published from 1980 to 1993 was conducted . Selected studies published before 1980 were also reviewed if there were no recent updates . Evidence was evaluated and classified as good, fair or poor according to the criteria of the task force . VALUES: The task force's evidence-based rules for recommendations were used . In addition, whenever feasible, and on the basis of advice from the reviewers and experts, recommendations were modified in the interest of maintaining oral health (e.g., dental flossing in children) . BENEFITS, HARMS AND COSTS: The recommendations are not expected to increase the costs of preventing periodontal diseases for the general population . They could benefit dental patients and reduce costs because they are based on the periodontal needs of patients rather than on the current universal application approach. Pharmacoeconomics, 1993 Dec, 4(6), 437 - 45 Drug utilisation in preterm and term neonates; Gortner L; Drug utilisation in term and preterm neonates (i.e . less than 28 days of age) has been investigated prospectively in 4 clinical studies during the past 10 years . 3880 neonates with a mean gestational age of 34.5 weeks (corresponding birthweight 2280g) were enrolled in these studies . An overview indicates a high prevalence of antibiotic treatment throughout the studies, ranging from 69% to virtually 100% . The highest prevalence was observed in studies enrolling only preterm neonates (gestational age less than 30 weeks) with need for mechanical ventilation . A further high prevalence of parenteral nutrition (84 to 100%), transfusion of blood products (91 to 100%) and vitamin use (16 to 78%) was described . Higher degrees of immaturity and rates of complications were associated with an increased drug usage up to a mean of 17 different drugs in very preterm (i.e . less than or equal to 30 weeks gestation) neonates with severe respiratory disorders and related complications . The high prevalence of antibiotic usage may be explained by the fact that clinical symptoms of neonatal bacterial infections are usually variable, and laboratory tests initially are not highly specific . Respiratory disorders in neonates are often associated with or caused by infections . Nosocomial infections in neonatal intensive care units further prompt administration of antimicrobial agents . Six prospective controlled clinical trials during the past 10 years have investigated treatment with dexamethasone of bronchopulmonary dysplasia, a chronic lung disease secondary to mechanical ventilation of surfactant-deficient lungs in very preterm neonates.(ABSTRACT TRUNCATED AT 250 WORDS) JAMA, 1993 Nov 3, 270(17), 2071 - 5 Long-term eradication of Chlamydia trachomatis genital infection after antimicrobial therapy . Evidence against persistent infection; Workowski KA et al.; OBJECTIVE--To determine whether Chlamydia trachomatis urogenital infections persist or relapse after antimicrobial therapy by serial measurement of chlamydial-specific DNA using the polymerase chain reaction (PCR), cell cultures, and serological studies . DESIGN--Prospective evaluation of an inception cohort . SETTING--University student health clinic . PARTICIPANTS--Twenty women with culture-proven and PCR-proven C trachomatis urogenital infections . MEASUREMENTS--Incidence of persistent infection as determined by PCR, culture, and serial measurement of local and systemic antibody to C trachomatis for 5 months after doxycycline therapy . RESULTS--Prior to therapy, C trachomatis was isolated in cell culture from the cervix in 19 of 20 women, from the urethra in 13 women, and from the rectum in 13 women . All culture-positive specimens were also PCR-positive . Immediately after completion of antimicrobial therapy, all women had negative cell cultures for chlamydia . Ten of 20 culture-negative cervical specimens and two culture-negative urethral specimens had chlamydial DNA present immediately after treatment . In addition, three women had detectable DNA from cervical specimens 1 week after treatment . The presence of cervicitis (P = .01), high inclusion counts (P = .004), and serological evidence of recent infection (P = .0004) were each significantly associated with PCR positivity after treatment . All 384 subsequent cervical, rectal, and urethral specimens collected over 5 months were negative by both PCR and culture with the exception of one woman who was reinfected . Serum immunoglobulin M (IgM) titers, geometric mean serum immunoglobulin G (IgG) titers, and prevalence of local antibody to chlamydia progressively declined after treatment . CONCLUSIONS--Standard antimicrobial therapy is effective in the long-term microbiologic eradication of uncomplicated C trachomatis urogenital infections . The presence of chlamydial DNA after antimicrobial therapy is of short duration and reflects excretion of nonviable organisms rather than persistent infection. Biochemistry, 1993 Nov 2, 32(43), 11704 - 10 Role of disulfide linkages in tachyplesin-lipid interactions; Matsuzaki K et al.; In order to elucidate the role of the two disulfide linkages of tachyplesin I (T-SS), a membrane-acting cyclic antimicrobial peptide from Tachypleus tridentatus, we synthesized the acyclic analog (T-Acm) with the four SH groups protected by acetamidomethyl groups and also investigated the interactions of these peptides with lipid bilayers . T-SS induced leakage of calcein from egg yolk L-alpha-phosphatidylglycerol large unilamellar vesicles (PG LUVs) at peptide concentrations 1 order of magnitude smaller than those at which leakage was induced by T-Acm, which coincides with the stronger antimicrobial activities of T-SS . The micellization of PG LUVs was also more efficient for the cyclic peptide . Fluorescence titration studies revealed that binding affinities of both peptides to the PG membranes were similar . Fourier transform infrared polarized attenuated total reflection spectroscopy and fluorescence quenching experiments demonstrated that T-SS and T-Acm both form amphiphilic antiparallel beta-sheet structures in the membranes . They are formed in such a way that the sheet planes lie parallel to the membrane surface with the sheet hydrophobic surfaces penetrating slightly into the hydrophobic region of the bilayers . Furthermore, the observation that the linear T-Acm, the weaker membrane permeabilizer, caused a far more serious membrane disruption suggests the possibility that the mechanisms of membrane permeabilization by the cyclic peptide are different from those by the linear peptide, the latter being the disruption of the lipid organization. J Calif Dent Assoc, 1993 Nov, 21(11), 51 - 6 Antimicrobial therapy in periodontics; Slots J et al.; Cause-related therapy in periodontics is aimed at the reduction or elimination of microbial pathogens . Periodontitis is associated with microflorae which may consist of indigenous, exogenous or superinfecting organisms . In general, periodontal infections due to indigenous organisms (endogenous or commensal infections) are treated by continual reduction of the bacterial load, exogenous infections (true infections) by adjunctive antibiotic therapy and superinfections (opportunistic infections) by a combined approach of conventional therapy and improvement of compromising host or environmental factors . Properly selected single drug, combination drug and serial drug therapies show great promise in the treatment of severe periodontitis Obstet Gynecol, 1993 Nov, 82(5), 765 - 8 Pelvic inflammatory disease in human immunodeficiency virus-infected women; Korn AP et al.; OBJECTIVE: To determine whether the clinical course of pelvic inflammatory disease differs between women with human immunodeficiency virus (HIV) infection and seronegative controls . METHODS: All admissions for acute pelvic inflammatory disease from January 1, 1986 to December 31, 1992 at San Francisco General Hospital were reviewed, identifying 23 HIV-seropositive women . Their clinical course was compared with a control group of 108 seronegative women admitted for acute pelvic inflammatory disease . RESULTS: Human immunodeficiency virus-seropositive women with acute pelvic inflammatory disease had significantly lower abdominal tenderness scores (P < .05), lower admission and discharge white blood cell counts (WBC) (P < .01, P < .05), and fewer gonococcal infections (odds ratio 0.3, 95% confidence interval {CI} 0.1-0.9; P < .05) than the seronegative controls . There were no significant differences in duration of treatment, length of hospitalization, or incidence of tubo-ovarian abscess . Significantly more HIV-positive women with acute pelvic inflammatory disease required surgical intervention than seronegative women (odds ratio 5.5, 95% CI 1.0-29.3; P < .05) . CONCLUSION: Human immunodeficiency virus-seropositive women with acute pelvic inflammatory disease may have an altered immune response, resulting in inadequate response to antimicrobial agents and the need for more surgical intervention . Future studies must include larger numbers of HIV-infected women, and the results must be stratified for CD4 counts, clinical HIV stage, and other measures of immunocompromise. J Urol, 1993 Nov, 150(5 Pt 2), 1722 - 4 Norfloxacin as prophylaxis against urethral strictures following transurethral resection of the prostate: an open, prospective, randomized study; Hammarsten J et al.; An open, prospective, randomized study was performed to investigate the effect of norfloxacin prophylaxis on stricture formation and operative outcome after transurethral resection of the prostate . After resection, the 359 patients studied were randomly divided into 2 groups: 1) those given norfloxacin as prophylaxis for 15 days following removal of the catheter (norfloxacin group) and 2) those given no antimicrobial prophylaxis during the same period (control group) . Of the patients 94 were excluded . At followup 6 to 12 months postoperatively, the number of strictures in the anterior urethra was 2 of 135 in the norfloxacin group and 22 of 130 in the control group (p < 0.01) . Strictures in the bladder neck developed in 3 of 135 and 4 of 130 patients, respectively (not significant) . As a consequence of a lower structure incidence in the anterior urethra in the norfloxacin group, fewer patients in that group were dissatisfied with the operative outcome . The results suggest that norfloxacin provides effective prophylaxis against stricture formation after transurethral resection of the prostate. Rozhl Chir, 1993 Nov, 72(8), 373 - 5 {Antimicrobial prophylaxis with cefamandole in biliary tract surgery}; Vyhnanek F et al.; The authors present their experience with antimicrobial prophylaxis using cephalosporin of the second generation--cefamandole--in biliary surgery . Cefamandole was administered to 28 patients operated for a biliary affection and hospitalized at the Surgical Clinic of the Third Medical Faculty in Prague . Cefamandole was administered after 8-hour intervals in 1 g doses up to 48 hours after the first dose . For antimicrobial prophylaxis patients were selected, included after previous investigations in the high risk group . In the patients in addition to microbiological examination of bile the cefamandole levels in bile and serum were compared . The presented results proved that cefamandole administration is justified in the prevention of infectious complications after operations of the gallbladder and biliary pathways because of its antibacterial and pharmacokinetic properties. Dig Dis, 1993 Nov-Dec, 11(6), 334 - 42 Pharmacotherapy of inflammatory bowel disease; Reynolds PD et al.; The standard treatments for inflammatory bowel disease have been aminosalicylates and corticosteroids, administered both systemically and topically . They are frequently extremely effective, especially at higher doses . Unfortunately steroid side effects are too frequent and agents with low systemic bioavailability (budesonide, beclamethasone and tixocortol) are being investigated . Azathioprine, although a useful adjunct to steroids, has occasional and unpredictable severe side effects . Cyclosporin is an important new therapy in severe refractory disease . Several new phospholipid mediator inhibitors, mepacrine, zileuton, and ridogrel, may be useful in moderate colitis . Other topical treatments, butyrate, acetarsol and bismuth subsalicylate, can be beneficial in refractory distal disease . Quadruple antimycobacterials, antioxidants and antimicrobials warrant further study, while newer immunosuppressives such as methotrexate, FK 506 and monoclonal antibodies against helper T lymphocytes show some early promise. Enferm Infecc Microbiol Clin, 1993 Nov, 11(9), 487 - 9 {Analysis of 40 cases of otomycosis}; Garcia-Martos P et al.; AIM: Otomycosis is a rare clinical process, with peculiar characteristics concerning its etiology and presentation, depending on the geographic area . In order to determine the most common agents, the clinical and epidemiological aspects in mycotic external otitis, 40 episodes detected during one year period were analyzed . METHODS: Forty patients with otomycosis diagnosed (positive microbiological culture) were studied . Fungi were identified in accordance with morphological and biochemical criteria . RESULTS: Candida parapsilosis (42.9%) and Aspergillus niger (35.7%) were the commonest agents . In three episodes were found associated bacterial flora . The patients were males (60.0%), between the ages of 31-40 (35.0%) and over 50 years old (37.5%) . The symptoms were the usual for these processes: serous fluid, otalgia and itching . The majority of the episodes occurred in the summer (57.5%) and autumn (30.0%), due to sea bathing (90.0%), trauma (27.5%) and prior antimicrobial treatment (40.0%) . CONCLUSIONS: Candida parapsilosis is as an important pathogen of otomycosis in our environment, though the participation of Aspergillus niger is also remarkable, as it happens in other geographic areas . The contact with seawater and the antimicrobial treatment are the main factors which favor the infection; climatical conditions could cooperate to it in great extent . The observed symptoms are similar to the bacterial otitis, but of lesser intensity. Pharmazie, 1993 Nov, 48(11), 837 - 41 {Stability and new formulations of hexetidine . 2 . Formulations and in vitro bioavailability}; Schmidt PC et al.; The solubilization of the water insoluble antimicrobial compound hexetidine is achieved by tensides and cyclodextrins . Using tensides the active ingredient is associated with the lipophilic part of the emulsifier . Tensides with a hydrophilic element in the lipophilic part of the molecule show better solubilizing properties . In contrast a higher stability is achieved with emulsifiers without hydrophilic elements in the lipophilic part of the molecule . The antimicrobial activity, determined by an in vitro test, is not influenced by the type of emulsifier . Cyclodextrins form inclusion complexes with hexetidine . Hydroxy propyl-beta-cyclodextrin is preferred due to its high water solubility . This inclusion complex shows compared with tenside solubilization a better taste and stability . The in vitro antimicrobial activity was comparable to tenside solubilized products. Pharmazie, 1993 Nov, 48(11), 808 - 11 Synthesis, anticonvulsant and antimicrobial activities of certain new furochromones; Ragab FA et al.; Some new substituted thiazolidinones, thioimidazolidinones and thiazolines have been synthesized from N1-substituted N2-(4-hydroxy-7-methyl-5H-furo{3,2-g} {1}benzopyran-5-on-9-yl)thioureas and monochloroacetic acid or alpha-halocarbonyl compounds . Some representative examples were tested for their anticonvulsant and antimicrobial activities. J Periodontol, 1993 Nov, 64(11 Suppl), 1166 - 70 The role of infection and anti-infection treatment in regenerative therapy; Newman MG; Infection associated with regenerative therapy is becoming an increasingly important consideration as the frequency and numbers of regenerative procedures increase . Specific recommendations for antimicrobial treatment associated with membranes, grafts, and implants are presented in the context of establishing general principles of infection management. Int J Clin Pharmacol Ther Toxicol, 1993 Nov, 31(11), 542 - 6 The application of new bioavailability parameters in the bioequivalence testing of antimicrobial agents; Wessels JC et al.; Two new bioavailability parameters were recently suggested {Koeleman et al . 1991} to define (i) the time that the concentration in the blood stays above a defined minimum effective concentration, te and (ii) the onset of the effect, to . In addition to conventional bioequivalence parameters, the new bioavailabilty parameters (to and te) were calculated in this study and statistically compared for penicillin, chloroquine, oxytetracycline, amoxycillin and flucloxacillin from available bioequivalence data . For oxytetracycline, flucloxacillin and amoxycillin, the conventional bioavailability parameters indicated partial equivalence whereas using the te and to parameters, more realistic indications of the possible extent of the performance of a drug from dosage forms were obtained than with the conventional bioequivalence parameters . The new parameters gave additional information for a better evaluation of the performance of a drug from a dosage form. J Nat Prod, 1993 Nov, 56(11), 1878 - 89 Antimicrobial compounds from Petalostemum purpureum; Hufford CD et al.; EtOH extracts of Petalostemum purpureum demonstrated antimicrobial activity against bacteria and fungi . Bioassay-directed fractionation led to the isolation of petalostemumol {1} as the active constituent . Its structure was determined by a single crystal X-ray diffraction analysis . A minor component designated petalostemumol G {3} is believed to be an artifact of the isolation procedure . Its structure was confirmed by a single crystal X-ray analysis of its pentamethylether 2 . A number of derivatives of 1 and 3, including the Me- and benzylethers and acetates, were prepared. Ginecol Obstet Mex, 1993 Nov, 61, 305 - 10 {Current concepts in the pathogenesis and treatment of abortion and septic shock I . The epidemiology, pathogenesis and management of septic abortion}; Figueroa Damian R et al.; In view of the illegal status induced abortion, it is difficult to determine the degree to which it is practiced . In our country there are a great inconsistency in the statistics on the number of abortions and the number of maternal deaths due to this cause . The principal complication of the illegal induced abortion is the septic abortion, with an uncontrolled bacterial infection and systemic complications that dominate the clinical picture . The mortality of the septic abortion is elevated, in the majority of cases due to septic shock . The treatment consist on antimicrobial agents and early surgery . A reduction on the number of illegal abortions will decrease significantly the number of septic abortion's cases. Ann Pharmacother, 1993 Nov, 27(11), 1378 - 82 Bacillary angiomatosis in a patient with AIDS; Teague AC et al.; OBJECTIVE: To report the clinical presentation and response to antimicrobial therapy of presumed bacillary angiomatosis in an AIDS patient . DESIGN: Single case report . SETTING: A 1058-bed, university teaching hospital . PATIENT: 28-year-old HIV-positive man (T4 lymphocyte count < 3/mm3), who was diagnosed with AIDS in 1984 . RESULTS: The skin lesions responded promptly to treatment with doxycycline and erythromycin . CONCLUSIONS: Bacillary angiomatosis is an infection that occurs with endstage AIDS . Skin lesions have recognizable characteristics and respond promptly to appropriate antibiotic therapy. Clin Infect Dis, 1993 Nov, 17(5), 854 - 6 Cytomegalovirus polyradiculopathy caused by a ganciclovir-resistant strain; Tokumoto JI et al.; Polyradiculopathy caused by cytomegalovirus (CMV) is a rare but serious neurological disorder that occurs late in the course of HIV-1 infection and is potentially treatable with antimicrobial agents active against CMV . We describe a patient with CMV infection caused by a strain that was resistant to ganciclovir . This case demonstrates one potential mechanism of therapeutic failure and illustrates the potential pathogenicity of strains that are resistant to antiviral drugs. Clin Infect Dis, 1993 Nov, 17(5), 850 - 3 Fatal Israeli spotted fever in children; Yagupsky P et al.; We describe three Israeli children with fatal spotted fever . Clinical disease was characterized by irreversible shock, encephalopathy, renal failure, bleeding tendency, and death within 24 hours of admission . None of the patients had a history of tick bite, and no tache noire was noted . One child presented without rash, and the other two did not have antibodies to spotted-fever-group rickettsiae . The disease was confirmed by isolation of Rickettsia conorii from the patients' blood and tissues in cell cultures or from susceptible laboratory animals inoculated with human specimens . The present cases demonstrate the existence of a severe form of Israeli spotted fever in this population that resembles Rocky Mountain spotted fever . Because Israeli spotted fever may follow a quick, unpredictable, rapidly fatal clinical course, specific antimicrobial therapy should be promptly administered whenever the diagnosis is suspected. Antimicrob Agents Chemother, 1993 Nov, 37(11), 2504 - 5 In vitro activities of antimicrobial agents against clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer; Rolston KV et al.; We evaluated the in vitro activities of 21 different antimicrobial agents against nine clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer . The organisms were susceptible to most agents commonly used for the empiric therapy (aminoglycosides, ureidopenicillins, extended-spectrum cephalosporins, monobactams, and carbapenems) and prevention of infections (quinolones and trimethoprim-sulfamethoxazole) in this patient population. Antimicrob Agents Chemother, 1993 Nov, 37(11), 2418 - 21 Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid fever related to outcome of antimicrobial therapy; Butler T et al.; To study mechanisms of antibiotic effects in typhoid fever, levels of interleukin-6 (IL-6), gamma interferon (IFN-gamma), and cytokine receptors (tumor necrosis factor receptor {TNF-R} p55 and TNF-R p75) were measured in the plasma of 29 adult Nepalese with culture-positive typhoid fever before therapy and on days 4 and 15 after start of therapy with either ceftriaxone at 2 g/day for 3 days or chloramphenicol at 50 mg/kg of body weight per day for 14 days . Bacteriologic cure was defined as blood cultures testing negative on days 4 and 15 after start of therapy; clinical cure was defined as symptomatic improvement within 5 days after start of therapy and absence of relapse . Clinical and bacteriologic cures occurred in 24 patients . There were two clinical failures, two patients who failed to complete therapy because of leukopenia, and one relapse . Mean levels before therapy were elevated compared with those in healthy controls (IL-6, 11.4 pg/ml; IFN-gamma, 1.3 ng/ml; TNF-R p55, 3.8 ng/ml; and TNF-R p75, 6.1 ng/ml) and fell progressively during and after therapy . For six patients (three in each treatment group) who showed prolonged fever (> 5 days) or relapse, mean levels of IL-6 and TNF-R p55 before therapy (29.5 pg/ml and 6.1 ng/ml, respectively) and on day 4 (17.7 pg/ml and 4.0 ng/ml) were significantly greater than corresponding means for 23 patients who showed early defervescence (on admission, 6.7 pg/ml and 3.3 ng/ml, and on day 4, 1.8 pg/ml and 2.7 ng/ml, P < .05) . These results indicate that the concentrations of plasma cytokines and their receptors are elevated in typhoid fever and that these concentrations can be useful in predicting outcome. Antimicrob Agents Chemother, 1993 Nov, 37(11), 2323 - 6 Activities of antimicrobial agents against clinical isolates of Mycobacterium haemophilum; Bernard EM et al.; Mycobacterium haemophilum, first described in 1978, can cause severe infections of skin, respiratory tract, bone, and other organs of immunocompromised patients . There is no standardized antimicrobial susceptibility test, and for the 27 reported cases, a variety of test methods have been used . This paper reports the in vitro test results for 17 isolates of M . haemophilum recovered from 12 patients in the New York City area . MICs of 16 antimicrobial agents were determined in microtiter trays containing Middlebrook 7H9 broth plus 60 microM hemin, inoculated with 10(6) CFU of the organism per ml and incubated at 30 degrees C for 10 days . Ethambutol, ethionamide, tetracycline, cefoxitin, and trimethoprim-sulfamethoxazole were inactive against initial isolates from the 12 patients . Isoniazid was weakly active with a MIC for 50% of strains tested (MIC50) of 8 micrograms/ml and a MIC90 of > 32 micrograms/ml . Three quinolones, ciprofloxacin, ofloxacin, and sparfloxacin, were moderately active with MIC50s of 2 to 4 micrograms/ml and MIC90s of 4 to 8 micrograms/ml . Amikacin and clofazamine were active with MIC90s of 4 and 2 micrograms/ml, respectively . Clarithromycin was the most active macrolide with a MIC90 of < or = 0.25 microgram/ml . The MIC90 of azithromycin was 8 micrograms/ml, and the MIC90 of erythromycin was 4 micrograms/ml . The rifamycins were active with a MIC90 of 1 microgram/ml for rifampin and one of < or = 0.03 micrograms/ml for rifabutin . For a second isolate from the skin of one patient and a isolate from an autopsy culture of the spleen of a second patient, MICs of rifampin and rifabutin were > 16 microgram/ml, whereas initial isolates were inactivated by low concentrations of the rifamycins . Both patients had been treated for several months with several antimicrobial agents, including a rifamycin. Can J Cardiol, 1993 Nov, 9(9), 833 - 6 Amiodarone-induced epididymitis: report of a new case and literature review of 12 cases; Sadek I et al.; OBJECTIVE: To report a new case and review the literature of amiodarone-related epididymitis to improve knowledge of the clinical characteristics of this reaction . DESIGN: Cohort study . SETTING: Tertiary out-patient arrhythmia clinic . PATIENTS: Males currently treated for arrhythmias with amiodarone for at least two months . Thirty-two patients were identified and all were contacted . OUTCOME MEASURES: Swelling and or/pain in the scrotum with confirmation of noninfectious epididymitis by a urologist . DATA SOURCES: Bibliography (Medline and Embase) and databases (Manufacturer, Health Protection Branch, World Health Organisation) . STUDY SELECTION: Four articles with case reports . Databases searched for these key words: amiodarone and epididymitis . RESULTS: A new case is reported . Twelve cases have been presented individually and six more described collectively . Times to onset range from four to 71 months, daily doses range from 200 to 800 mg . The reaction is self-limited, with or without amiodarone reduction, and does not require antimicrobial drugs, but a noninvasive urological examination may be warranted . CONCLUSION: Awareness by cardiologists will prevent unnecessary invasive urological investigations or antibiotic therapy. Drug Saf, 1993 Nov, 9(5), 346 - 64 Adverse effects of macrolide antibacterials; Periti P et al.; The renewed interest in macrolide antibacterials with expanded indications for clinical use, as well as their markedly increased usage, justifies the continuous search for new compounds designed to offer the patient not only enhanced bioavailability but also a reduced incidence of adverse effects . Macrolides are an old and well established class of antimicrobial agents that account for 10 to 15% of the worldwide oral antibiotic market . Macrolides are considered to be one of the safest anti-infective groups in clinical use, with severe adverse reactions being rare . Newer products with improved features have recently been discovered and developed, maintaining or significantly expanding the role of macrolides in the management of infection . This review deals with the tolerability of the clinically available macrolide antibacterials . With the exception of drug interactions, adverse effects have been analysed during the last 40 years in many thousands of adult and paediatric patients . Recently developed derivatives have been compared with the older compounds, and the expected and well assessed adverse effects have been set apart from those which are unusual, very rare or questionable . Gastrointestinal reactions represent the most frequent disturbance, occurring in 15 to 20% of patients on erythromycins and in 5% or fewer patients treated with some recently developed macrolide derivatives that seldom or never induce endogenous release of motilin, such as roxithromycin, clarithromycin, dirithromycin, azithromycin and rikamycin (rokitamycin) . Except for troleandomycin and some erythromycins administered at high dose and for long periods of time, the hepatotoxic potential of macrolides, which rarely or never form nitrosoalkanes, is low for josamycin, midecamycin, miocamycin, flurithromycin, clarithromycin and roxithromycin; it is negligible or absent for spiramycin, rikamycin, dirithromycin and azithromycin . Transient deafness and allergic reactions to macrolide antibacterials are highly unusual and have definitely been shown to be more common following treatment with the erythromycins than with the recently developed 14-, 15- and 16-membered macrolides . There have been case reports in the literature of 51 patients during the last 30 years who experienced uncommon or dubious adverse effects after treatment with older compounds and in which there appears to be strong evidence of a causal relationship with the drug . Only 3 cases had an unfavourable outcome, and these were patients administered erythromycin lactobionate intravenously too rapidly or at high dose . Targets of these occasional reactions are generally the heart, liver and central nervous system . Other unusual organ pathologies are related to immunomediated disorders more than to primary parenchymal toxicity, or to the rarely serious consequences of macrolide-induced alterations in intestinal microflora.(ABSTRACT TRUNCATED AT 400 WORDS) Clin Infect Dis, 1993 Nov, 17 Suppl 2, S537 - 49 Adjunctive therapy for bacterial meningitis: rationale for use, current status, and prospects for the future; Townsend GC et al.; Despite the introduction of numerous therapeutic advances, the morbidity and mortality associated with bacterial meningitis remain significant . Research into the pathophysiology of bacterial meningitis has revealed that the inflammatory response resulting from bacterial invasion of the subarachnoid space is due in large part to the activity of host-derived mediators . This inflammatory response is ultimately responsible for the long-term neurological sequelae and death associated with bacterial meningitis . In vitro and in vivo models of bacterial meningitis have identified several points in the inflammatory cascade that may be amenable to therapeutic intervention . Numerous potential therapeutic agents that may limit inflammation of the subarachnoid space have been and are being developed, and trials in animal models and in humans are under way . The judicious use of safe and effective agents with demonstrated efficacy as adjuncts to bactericidal antimicrobial agents in the therapy for bacterial meningitis in humans may improve the prognosis of this disease. Clin Infect Dis, 1993 Nov, 17 Suppl 2, S447 - 54 The diagnostic mycobacteriology laboratory of the 1990s; Kiehn TE; The diagnostic mycobacterial laboratory of the 1990s must respond to a change in the clinical spectrum of mycobacterial infections brought about by an increase in the number of patients who are immunocompromised, are indigent, or have temporary or permanent implanted devices . Emerging pathogens such as Mycobacterium haemophilum and Mycobacterium genavense, multidrug-resistant strains of Mycobacterium tuberculosis, and catheter infections with rapidly growing mycobacteria are examples of new issues . Fortunately, new methods for detection and identification of microbes have been or are being developed . Procedures that, when applied directly to clinical specimens or actively growing cultures, dramatically reduce the time to diagnosis of mycobacterial infections include radiometric broth, lysis-centrifugation, and biphasic systems for specimen culture, and DNA probes, high-performance liquid chromatography, DNA hybridization, restriction fragment length polymorphism, and gene amplification for organism detection and identification . At present, in vitro antimicrobial susceptibility tests are most helpful in guiding treatment of infections caused by M . tuberculosis and rapidly growing mycobacteria. Clin Infect Dis, 1993 Nov, 17 Suppl 2, S436 - 41 Mycobacterial diseases and the compromised host; Young LS; Tuberculosis due to Mycobacterium tuberculosis and other mycobacteria should be considered in the diagnostic approach to febrile immunocompromised patients . In patients with AIDS, organisms of the Mycobacterium avium complex (MAC) are the most common bacterial causes of disseminated infection . Effective means of both treating and preventing disseminated MAC infections have been developed that use regimens including the new macrolides, aminoglycosides, and rifamycins . Antimicrobial agents active against M . tuberculosis are not usually active against MAC organisms, and the converse may also be true . With the advent of more cases of drug-resistant tuberculosis, however, the urgency regarding development of new therapeutic approaches for tuberculosis is widely appreciated . Research into the pathogenesis and treatment of infections due to M . tuberculosis and MAC, which has been much neglected, is likely to provide new knowledge that will benefit the clinical approach to all mycobacterial diseases. Clin Infect Dis, 1993 Nov, 17 Suppl 2, S407 - 13 Cytokines as antimicrobial therapy for the T cell-deficient patient: prospects for treatment of nonviral opportunistic infections; Murray HW; Patients rendered T cell-deficient by advanced disease due to human immunodeficiency virus, an underlying neoplastic disorder, or immunosuppressive therapy are vulnerable to a select group of opportunistic infections . These infections, which often fail to respond to conventional therapy, provide the clinical setting in which the efficacy of treatment with cytokines can be tested . Particularly pertinent cytokines are those that activate macrophages and monocytes or enhance T-cell function . Experimental observations and emerging data from patients with intact T-cell function suggest that treatment with at least three cytokines, interferon-gamma, interleukin-2, and granulocyte-macrophage colony-stimulating factor (GM-CSF) may be of benefit . Each of these cytokines is already in clinical use, and each has therapeutic potential in a variety of different infectious disease . Patients with infections caused by opportunistic intracellular pathogens appear to be the most appropriate candidates for adjunctive cytokine therapy. J Antibiot (Tokyo), 1993 Nov, 46(11), 1658 - 65 IC101, extracellular matrix antagonist produced by Streptomyces sp . MJ202-72F3 . Production, isolation, structure determination and biological activity; Ueno M et al.; In our search for inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin, laminin and collagen type IV, we succeeded in finding a novel cyclic hexadepsipeptide antibiotic, named IC101, which was isolated from cultured mycelium of Streptomyces albulus MJ202-72F3 . It was purified by centrifugal partition chromatography, preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder . IC101 strongly inhibited cell adhesion to ECM components, suppressed immune responses in vitro and in vivo, and exhibited antimicrobial activity on Gram-positive bacteria. Eur J Vasc Surg, 1993 Nov, 7(6), 638 - 41 A national audit of antimicrobial prophylaxis in vascular surgery; Winslet MC et al.; A standard questionnaire on antimicrobial prophylaxis for elective and emergency vascular surgery was sent to 262 practising members of the Association of Vascular Surgeons (U.K.) . The response rate was 68.3% . A cephalosporin based regime was used in 61.1% of cases while penicillin was used in 39.3% and an aminoglycoside in 6.5% . More than one antibiotic was routinely used in 15.6% of cases, with specific anti-anaerobic cover in 19% . Prophylaxis was used in all cases using a prosthetic graft, but in only 76% of cases using autogenous vein (p < 0.05) . A single dose regime was most commonly used for autogenous vein graft (14% vs . 4.5%, p < 0.05), whilst overall a three dose regime was most popular . Some 2.8% of respondents specified a differing regime for supra- and infrainguinal surgery whilst 4.5% modified their regime in emergency cases . Despite its theoretical limitations, a three dose cephalosporin regime is the most commonly prescribed "prophylactic" regime for all forms of vascular surgery in the U.K. Am J Hosp Pharm, 1993 Nov, 50(11), 2343 - 7 Multidisciplinary task force for controlling drug expenses; Hayman JN et al.; The establishment of a multidisciplinary task force to control increasing drug costs is described . From 1986 to 1992, dollars spent on drugs at a 964-bed teaching hospital increased from $9.8 million to $26.8 million, despite a tightly controlled formulary, prudent purchasing practices, prescribing restrictions, an antimicrobial order form program, a target-drug program, and an active pharmacy-run cost intervention program . These increases occurred as a result of changes in the mix of drugs prescribed, increases in outpatient volume, inflation, and price increases resulting from the Omnibus Budget Reconciliation Act of 1990 . A multidisciplinary task force composed of seven teams--AIDS and related issues, ambulatory care, medicine, obstetrics and gynecology, pediatrics, surgery, and systems and procedures--was formed to identify ways to reduce drug expenses and enhance revenue . Each team made recommendations designed to reduce the rate of growth of pharmaceutical expenses . To implement these recommendations, the task force used a variety of verbal and written strategies to educate and communicate with physicians, pharmacists, nurses, pharmaceutical company representatives, and patients . A system was developed so that goal achievement could be monitored . The program, which was implemented on September 16, 1991, and continued through September 30, 1992, reduced the growth in drug expense by $2.33 million . As a result of the program, control of the drug expenses became an institutional priority, not merely a pharmacy department priority . By establishing a multidisciplinary team approach involving physicians, administrators, nurses, and pharmacists, a substantial reduction in the growth of drug expenses can be achieved. Kekkaku, 1993 Nov, 68(11), 715 - 21 {The immunology of mycobacterial diseases}; Ando M; Protection and pathogenesis of tuberculosis greatly depend on specific T lymphocytes . Recent evidence suggests the existence of at least two pathways of acquired specific resistance to M . tuberculosis infection: The first consists of cytokine-mediated activation of infected host cells by protective CD4+ T cells, which are currently believed to mediate antimicrobial activity via the release of macrophages activating cytokines such as IFN-gamma and TNF-alpha . The second involves the lysis of these infected cells by cytotoxic effector CD4+ T cells, which is class II MHC restricted, requires cell-to-cell contact mediated by the ICAM-1 and LFA-1 ligand pair, and appears to be independent of lymphotoxins and through the direct cell interaction by adhesion molecules such as LFA-1 and ICAM-1 but not cytokines . On the other hands, gamma delta T cells might be part of the primary response to infection with live M . tuberculosis . gamma delta T cells have the potential to express cytotoxicity for mononuclear phagocytes pulsed with mycobacterial antigens, and are capable of secreting a variety of cytokines, including IL-2 and IFN-gamma . Intracellular killing mechanisms by activated macrophages are still unknown . Recently, increasing attention has been focused on the role of NO as a mediator of a number of physiological reaction . Activated macrophages appear to exhibit some antimicrobial actions as well as antitumor effects via generation of NO, which depends on the L-arginine oxidation pathway . However, it is still unknown whether or not human macrophages generate NO radicals.(ABSTRACT TRUNCATED AT 250 WORDS) J Clin Microbiol, 1993 Nov, 31(11), 3001 - 6 Typing of strains from a single-source outbreak of Pseudomonas pickettii; Dimech WJ et al.; Plasmid profiles, genome restriction fragment polymorphisms, carbohydrate oxidation-fermentation reactions, methylumbelliferyl substrate hydrolysis patterns, antimicrobial susceptibilities, and results obtained with the Biolog GN biochemical substrate kit were used to type 19 common-source, but mixed-biotype, outbreak strains and one epidemiologically distinct strain of Pseudomonas pickettii . Biotyping with conventional and methylumbelliferyl substrates failed to distinguish between strains . Plasmid profile testing was found to be inconsistent and not reproducible . The Biolog GN kit allowed greater strain differentiation than restriction fragment polymorphism did (12 biotypes versus 5 biotypes); antimicrobial susceptibility testing yielded 4 biotypes, and oxidation-fermentation tests gave 3 biotypes . Oxidation-fermentation results were consistent with restriction fragment polymorphs in all but 1 of the 20 strains tested . For ease of typing, comprehensive typeability, and reproducibility, oxidation-fermentation tests should be performed initially and followed if necessary by restriction fragment polymorph analysis for the elucidation of P . pickettii infection outbreaks. J Periodontal Res, 1993 Nov, 28(6 Pt 1), 420 - 8 Chemically-modified tetracycline normalizes collagen metabolism in diabetic rats: a dose-response study; Yu Z et al.; An earlier study indicated that a chemically-modified non-antimicrobial tetracycline (4-de-dimethylaminotetracycline; CMT-1) can inhibit excess collagenase activity in the connective tissues of diabetic rats, however, the optimum oral dose and resulting serum concentration were not determined . In the current study, adult male Sprague-Dawley rats (body weight approx . 350 g) were made diabetic by streptozotocin injection and administered by oral gavage either 0, 1, 2, 5, or 10 mg CMT-1 per day . After 3 weeks of drug therapy, the rats were killed and gingiva, skin, and serum collected . The tissues were 1) extracted, partially purified and analyzed for collagenase activity using {3H-methyl} collagen as substrate and SDS-PAGE/fluorography; 2) extracted in neutral salt and dilute acid solutions (4 degrees C) to assess collagen solubility; and 3) analyzed for hydroxyproline to determine tissue (skin) collagen mass . Serum was analyzed for glucose and CMT-1 concentration, the latter by HPLC . Inducing diabetes dramatically increased both gingival and skin collagenase activity and reduced skin collagen mass by 69.8% . Increasing the oral dose of CMT-1 progressively increased the serum concentration of the drug from 0.6-6.5 micrograms/ml and progressively decreased the excessive collagenase activity in gingiva and skin (p < 0.01 vs untreated diabetics) . Although skin collagen mass tended to be increased at all oral doses of CMT-1, only the 5 mg dose effect was statistically significant (p < 0.01) . The diabetes-induced reduction in collagen solubility, a classic abnormality (reflecting excessive collagen crosslinking) of this disease, was also normalized by CMT-1 therapy.(ABSTRACT TRUNCATED AT 250 WORDS) J Am Vet Med Assoc, 1993 Nov 1, 203(9), 1324 - 9 Neonatal septicemia in calves: 25 cases (1985-1990); Aldridge BM et al.; Historical, physical, and clinicopathologic findings in 25 septicemic calves were examined to further characterize the clinical features of naturally induced bovine neonatal septicemia . Owners often reported single organ disease, but physical examination revealed multiple organ disease in more than half the calves . A third of the calves were admitted as representative of a herd problem . Laboratory findings were variable, but commonly included changes in the differential WBC count and plasma fibrinogen concentration . Low serum immunoglobulin concentrations were found in approximately half the calves . Escherichia coli was the most frequently isolated organism, but gram-positive infections were found in 10%, and polymicrobial infections in 28%, of the calves . Previous antimicrobial administration did not appear to affect culture yield . At necropsy, lesions were seen in multiple organs in most calves . The respiratory and gastrointestinal systems were most commonly affected . Few of the calves had umbilical infections . The survival rate was poor (< 12%). Vet Clin North Am Food Anim Pract, 1993 Nov, 9(3), 609 - 20 Antibiotic residue tests for mammary gland secretions; Cullor JS; Current control methods are not effective in eliminating various mastitis pathogens, and antimicrobial therapy introduces some risk of contaminating dairy products with antibiotic residues . Individuals involved in animal agriculture are sensitive to their responsibility to prevent antibiotic residues from entering the food chain . The ability to understand and perform the appropriate screening systems for determining the residue status of an individual animal, bulk tank, or tanker truck sample provides an opportunity to practice residue management and enhance the quality of dairy products available to the consumer. Vet Clin North Am Food Anim Pract, 1993 Nov, 9(3), 499 - 517 Advances in the therapy for mastitis; Erskine RJ et al.; Methods to enhance mammary resistance to bacterial infection and to reduce the effects of existing infections without the use of antimicrobial agents are becoming more attractive, primarily because of increasing pressure from consumers and regulatory agencies to decrease the risk of drug residues in milk . Because of the difficulty in obtaining satisfactory results with existing drug formulations, new approaches in the treatment of mastitis should emphasize better understanding of mammary gland pharmacokinetics, ameliorating the pathologic effects of infection, and enhancing natural defenses . Effica