Quintessence Int, 2004 Oct, 35(9), 723 - 7 Aspects of oral syphilis; Landes CA et al.; The incidence of sexually transmitted diseases recently increased in the United States and Europe due to migration, increase in high-risk behavior, and abandonment of safer sex practices at the advent of anti-retroviral combination therapy for human immunodeficiency virus infection . This article presents four cases of primary oral anti perioral syphilis with differential diagnoses . It is important to bear this reappearing infection in mind to avoid latent infection . Resembling common oral infections, the primary affect disappears spontaneously, and the infection enters the second stage . The patient remains infected, may further spread the disease, and risks severe organ damage from long-standing infection . The antibiotic cure is inexpensive and safe and spares the patient mucous patches and gumma residuals, apart from severe general sequelae such as thoracic aorta aneurysm and neurosyphilis . However, compliance problems jeopardize clinical and serologic follow-up . The growing syphilis incidence prompts the commemoration of Dr Moriz Kaposi and his dispositive 1891 book Pathology and Therapy of the Syphilis . Moriz Kaposi is acknowledged as one of the heads of the Vienna School of Dermatology, a superb clinician, and renowned teacher. Intern Med, 2004 Aug, 43(8), 674 - 8 Influence of inhaled corticosteroids on community-acquired pneumonia in patients with bronchial asthma; To M et al.; OBJECTIVE: The aim of the present study was to evaluate the influence of inhaled corticosteroids (ICS) on community-acquired pneumonia (CAP) in patients with asthma . PATIENTS AND METHODS: All asthmatic patients who required hospitalization for CAP from the beginning of 1989 through December 2001 were enrolled in this retrospective study . Patients who used oral corticosteroids daily were excluded . Patients were divided into two groups based on whether or not they used ICS, and we analyzed clinical characteristics of the pneumonia . Sixty-two patients (28 males, 34 females; mean age, 54.5 years) were enrolled in this study . Thirty-seven of 62 patients used ICS, with the mean dosage being 777.9 microg/day . RESULTS: We found no significant differences between the two groups with regard to mean age, serum albumin level, duration of asthma, pulmonary function and frequency of intravenous infusion of corticosteroids in the outpatient department . There were no significant differences in body temperature, white blood cell count, and CRP value upon admission between the two groups . Differences were not significant in the period of resolution of the pneumonia or in the frequency of pathogens identified between the two groups . CONCLUSION: ICS therapy appears to have no influence on CAP in patients with asthma . We recommend that ICS should be continued to control asthma with adequate antibiotic therapy when asthmatic patients have CAP. Minerva Anestesiol, 2004 Sep, 70(9), 651 - 9 Tracheomalacia associated with Mounier-Kuhn syndrome in the Intensive Care Unit: treatment with Freitag stent . A case report; Giannoni S et al.; Tracheomalacia is a process characterized by softness of the supporting tracheal cartilages, by the extension of the posterior membranous wall and by reduction of the tracheal antero-posterior diameter . Exceptionally, tracheomalacia can be associated with tracheobronchomegaly or Mounier-Kuhn syndrome . Fibro-bronchoscopy represents the ''gold standard'' for diagnosis . The case of a 79-year-old male observed after hospitalization in a medical ward for chronic pulmonary obstructive disease (COPD) decompensation, and with basal left bronchopulmonary focus, is described . During this period, a progressive worsening of clinical conditions occurred, despite cortisone and antibiotic therapy, and the patient was transferred to the ICU for dyspnea, hypoxia, hypocapnia and with a diagnosis of pulmonary fibrosis . Bronchoscopy, performed during spontaneous breathing, revealed tracheomalacia which was responsible for tracheal dynamic complete stenosis during expiration and dynamic subtotal stenosis of the left primary bronchus in the first tract, together with sputum retention . Moreover, this investigation confirmed the diagnosis of tracheobronchomegaly already seen on CT . It was suggested to place a Freitag stent, since the insertion of another model would not have had enough chance of stability, due to the enormous extension of the tracheal lumen and could not have guaranteed good clearance of the secretions . Seven days after this intervention, performed in an outpatients' setting, the patient was dismissed from the ICU, without the help of O2, with good ventilation, saturation in line with his age and good expectoration. Nucleic Acids Res, 2004 Oct 05, 32(17), 5303 - 9 Print 2004. A novel GTPase activated by the small subunit of ribosome; Himeno H et al.; The GTPase activity of Escherichia coli YjeQ, here named RsgA (ribosome small subunit-dependent GTPase A), has been shown to be significantly enhanced by ribosome or its small subunit . The enhancement of GTPase activity was inhibited by several aminoglycosides bound at the A site of the small subunit, but not by a P site-specific antibiotic . RsgA stably bound the small subunit in the presence of GDPNP, but not in the presence of GTP or GDP, to dissociate ribosome into subunits . Disruption of the gene for RsgA from the genome affected the growth of the cells, which predominantly contained the dissociated subunits having only a weak activation activity of RsgA . We also found that 17S RNA, a putative precursor of 16S rRNA, was contained in the small subunit of the ribosome from the RsgA-deletion strain . RsgA is a novel GTPase that might provide a new insight into the function of ribosome. Comp Biochem Physiol B Biochem Mol Biol, 2004 Oct, 139(2), 225 - 34 Lactose causes heart arrhythmia in the water flea Daphnia pulex; Campbell AK et al.; The cladoceran Daphnia pulex is well established as a model for ecotoxicology . Here, we show that D . pulex is also useful for investigating the effects of toxins on the heart in situ and the toxic effects in lactose intolerance . The mean heart rate at 10 degrees C was 195.9+/-27.0 beats/min (n=276, range 89.2-249.2, >80% 170-230 beats/min) . D . pulex heart responded to caffeine, isoproteronol, adrenaline, propranolol and carbachol in the bathing medium . Lactose (50-200 mM) inhibited the heart rate by 30-100% (K(1/2)=60 mM) and generated severe arrhythmia within 60 min . These effects were fully reversible by 3-4 h . Sucrose (100-200 mM) also inhibited the heart rate, but glucose (100-200 mM) and galactose (100-200 mM) had no effect, suggesting that the inhibition by lactose or sucrose was not simply an osmotic effect . The potent antibiotic ampicillin did not prevent the lactose inhibition, and two diols known to be generated by bacteria under anaerobic conditions were also without effect . The lack of effect of l-ribose (2 mM), a potent inhibitor of beta-galactosidase, supported the hypothesis that lactose and other disaccharides may affect directly ion channels in the heart . The results show that D . pulex is a novel model system for studying effects of agonists and toxins on cell signalling and ion channels in situ. Toxicol In Vitro, 2004 Dec, 18(6), 901 - 5 Effect of recombinant interferon-alpha on streptozotocin-induced chromosome aberrations and sister-chromatid exchanges in hamster cells; Bolzan AD et al.; We assessed the effect of recombinant IFN-alpha-2a (rIFN-alpha-2a) on the induction of CAs and sister-chromatid exchanges (SCEs) by the methylating compound streptozotocin (STZ), in Chinese Hamster Ovary (CHO) cells . The cytokine was added to cell cultures 30 min before STZ and left in the culture medium until the end of the treatment . A statistically significant increase in the frequency of CAs and SCEs was observed following treatment with STZ alone (p < 0.05) compared to control, whereas treatments with rIFN-alpha-2a alone did not produce any significant increase of CAs or SCEs over the control values (p < 0.05) . Moreover, rIFN-alpha-2a had a marked inhibitory effect on the frequency of STZ-induced CAs--both chromosome- and chromatid-type--(p < 0.05) but was unable to prevent SCEs induced by the antibiotic (p > 0.05) . A decrease in the replication index (RI) was observed in the combined treatments compared with STZ alone-treated cultures, indicating inhibition of DNA synthesis . It is suggested that rIFN-alpha-2a exerts its protective action against the induction of CAs by STZ by stimulating DNA repair. Toxicol In Vitro, 2004 Dec, 18(6), 821 - 7 Studies on the joint cytotoxicity of Wheat Germ Agglutinin and monensin; Dalla Pellegrina C et al.; Wheat Germ Agglutinin (WGA) cytotoxicity has been studied using two human leukemia cell lines, Molt3 and K562, and human peripheral blood mononuclear cells (PBMC) . In spite of similar binding at the cell surface, WGA was found to promote cell death to a different extent in Molt3, K562 and PBMC and to induce different death events leading to apoptosis in Molt3 and either apoptosis and necrosis in K562 cells and PBMC . In Molt3 but not in K562 cells, WGA cytotoxicity could be potentiated 66-200 fold by 50 nM monensin, a carboxylic ionophore that perturbs the intracellular trafficking of endocytosed molecules . Synergism between the cytotoxic activities of WGA and monensin was demonstrated in Molt3 cells by comparing non toxic, or slightly toxic, doses of WGA and monensin alone or in combination . These results show that the cytotoxic effect of WGA is dependent on internalisation events which may differ among the cell lines used . WGA and monensin can enter the human diet being a component of wheat germ and an antibiotic used for zootechnic reasons in the bioindustry, respectively . These data reveal the synergistic effect between two dietary molecules, otherwise per se toxic at much higher concentrations, with possible implications for human and animal health. Arch Biochem Biophys, 2004 Nov 1, 431(1), 88 - 94 ATP, histidine or magnesium ions can protect DNA against sisomicin-induced damage, following stray Cu(II) binding; Szczepanik W et al.; The oxidative DNA damage by the cupric complexes of sisomicin was investigated in the presence of varying amounts of histidine, ATP, Mg(II) ions or phosphates . We found that by very low concentrations, the amino acid is able to inhibit the cleavage totally . This occurs both by its competition with antibiotic for copper(II) binding, what was proved by spectroscopic measurements, as well as by ROS scavenging by the imidazole ring . ATP and magnesium also exert an influence on the yield of the DNA destruction by decreasing the amount of the single strand breaks, however only their significant excess is able to break this process . The influence of ATP on the plasmid damage has in this case a similar chemical mechanism to that one observed for histidine . Mg(II) ions, however, interact with DNA and thus prevent the complex binding . Only phosphate anions, in the range of their physiological concentrations, exert no influence on the cleavage process. J Cyst Fibros, 2004 Jun, 3(2), 67 - 91 Early intervention and prevention of lung disease in cystic fibrosis: a European consensus; Doring G et al.; In patients with cystic fibrosis (CF), early intervention and prevention of lung disease is of paramount importance . Principles to achieve this aim include early diagnosis of CF, regular monitoring of the clinical status, various hygienic measures to prevent infection and cross-infection, early use of antibiotic courses in patients with recurrent or continuous bacterial colonisation and appropriate use of chest physiotherapy. J Cyst Fibros, 2002 Sep, 1(3), 146 - 7 Falsely elevated serum tobramycin levels in a patient receiving nebulised tobramycin; Struthers SL et al.; It is common when treating patients with respiratory exacerbations of cystic fibrosis to use both nebulised and intravenous antibiotics . Aminoglycoside drug levels are often measured from finger-prick blood samples . We describe a case of a 14-year-old girl treated simultaneously with IV and nebulised tobramycin in whom drug levels, measured from finger prick blood samples, were erroneously high due to finger contamination by the nebulised drug . Special precautions or direct venepuncture is essential when assessing antibiotic levels in such patients. J Cyst Fibros, 2002 Jun, 1(2), 90 - 3 Pilot safety study of liposomal prostaglandin (PGE1) in respiratory exacerbations in cystic fibrosis; Taylor CJ et al.; BACKGROUND: A pilot evaluation to assess the safety and possible benefits of TLC C-53, (prostaglandin E(1) associated with egg phosphatidylcholine liposomes) in acute respiratory exacerbations in children with cystic fibrosis (CF) . METHODS: Randomised, double-blind, placebo-controlled study in 20 P . aeruginosa colonised patients . All received intravenous antibiotics . Subjects were given a rising dose of TLC C-53 (0.15-1.8 microg/kg) by 4 x 1-h infusions . Primary outcome measures were sputum IL-6, IL-8 and sputum neutrophil elastase . The rate of decline in lung function was determined at 6 weeks post-therapy as was the interval until the next respiratory exacerbation requiring intravenous antibiotic therapy . RESULTS: Analysis of primary and secondary outcome measures failed to show any significant differences between the two groups, although trends favoured the treated group . Decline in lung function over 6 weeks favoured the TLC C-53 group (FEV(1) mean difference 4.3%, 95% CI=-6.8, 15.4%) . Time to next exacerbation also favoured the TLC C-53 group with a mean time to exacerbation for TLC C-53 of 26.0 weeks against 11.9 weeks . CONCLUSIONS: A larger multi-centre trial of TLC C-53 as an adjunct to antibiotic therapy in respiratory exacerbations in CF would appear warranted. BMC Health Serv Res . 2004 Oct 05;4(1):28. Patients' perspectives on high-tech home care: a qualitative inquiry into the user-friendliness of four technologies; Lehoux P; BACKGROUND: The delivery of technology-enhanced home care is growing in most industrialized countries . The objective of our study was to document, from the patient's perspective, how the level of user-friendliness of medical technology influences its integration into the private and social lives of patients . Understanding what makes a technology user-friendly should help improve the design of home care services . METHODS: Four home care interventions that are frequently used and vary in their technical and clinical features were selected: Antibiotic intravenous therapy, parenteral nutrition, peritoneal dialysis and oxygen therapy . Our qualitative study relied on the triangulation of three sources of data: 1) interviews with patients (n = 16); 2) interviews with carers (n = 6); and 3) direct observation of nursing visits of a different set of patients (n = 16) . Participants of varying socioeconomic status were recruited through primary care organizations and hospitals that deliver home care within 100 km of Montreal, the largest urban area in the province of Quebec, Canada . RESULTS: The four interventions have both a negative and positive effect on patients' lives . These technologies were rarely perceived as user-friendly, and user-acceptance was closely linked to user-competence . Compared with acute I.V . patients, who tended to be passive, chronic patients seemed keener to master technical aspects . While some of the technical and human barriers were managed well in the home setting, engaging in the social world was more problematic . Most patients found it difficult to maintain a regular job because of the high frequency of treatment, while some carers found their autonomy and social lives restricted . Patients also tended to withdraw from social activities because of social stigmatization and technical barriers . CONCLUSIONS: While technology contributes to improving the patients' health, it also imposes significant constraints on their lives . Policies aimed at developing home care must clearly integrate principles and resources supporting the appropriate use of technology . Close monitoring of patients should be part of all technology-enhanced home care programs. Kidney Int Suppl, 2004 Oct, (91), S20 - 7 Renal water reabsorption: a physiologic retrospective in a molecular era; Schafer JA; The cloning and sequencing of the aquaporin water channels has been an enormous advance in the biomedical sciences, as recognized by the award of the Nobel Prize to Peter Agre last year . Among many other examples, expression of aquaporin proteins in Xenopus oocytes and other heterologous expression systems has confirmed two important models of renal function: the increase in the water permeability of the collecting duct by antidiuretic hormone (ADH), and the mechanism of near isosmotic volume reabsorption by the proximal tubule . These mechanisms were the subjects of intensive investigation by numerous investigators, including Thomas E . Andreoli, who is being honored by this symposium, and who developed many of the key concepts in these areas . His early work with artificial lipid bilayer membranes and the pore-forming antibiotic amphotericin provided the rigorous foundation in experimental and conceptual modeling techniques that he later applied to physiologic and pathophysiologic mechanisms in the kidney, which are summarized in this retrospective . Dr . Andreoli and his colleagues proposed a water channel mechanism for the action of ADH, which has been confirmed by the cloning and heterologous expression of aquaporin-2 . They also proposed that volume reabsorption by the proximal tubule depended on a very high hydraulic conductivity and the development of luminal hypotonicity produced by active solute reabsorption . This model has also been confirmed in mice in which aquaporin-1 expression is knocked out, resulting in a low proximal tubule water permeability that exaggerates the development of luminal hypotonicity. Biofizika, 2004 Jul-Aug, 49(4), 674 - 9 {The incorporation of rifampicin into multilayer and monolayer vesicles (liposomes) of different phosholipid composition}; Choosing abdominal incision and closure techniques: a review; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Medicine, State University of New York at Stony Brook, USAThis review summarizes contemporary concepts of abdominal surgical incision creation and closure . The Ovid computerized database was searched for articles published in English from 1996 to 2003 using keywords pertaining to the specific topic of interest (e.g., suture, drain, surgical technique, fascia) . Human prospective, randomized trials; meta-analyses; and evidence-based-focused reviews were assessed and data abstracted . Several earlier and animal-based studies on specific issues were included . The data indicate that: (1) the direction of the incision should be based upon obtaining adequate exposure; (2) hair should either be left in place or clipped at the time of surgery; (3) a single dose of prophylactic antibiotics should be given 30 minutes prior to surgery; (4) using a "deep" scalpel is unnecessary; (5) a scalpel and electrocautery are comparable for deepening the incision; (6) minimal peritoneal lavage with non-antibiotic containing solutions is adequate; (7) the peritoneum should not be routinely closed; (8) the fascia should be loosely approximated by a continuous mass closure using a slowly absorbable, monofilament suture with the smallest possible caliber and a suture:wound length ratio of at least 4:1; (9) retention sutures, subcutaenous sutures and drains do not appear to reduce the risk of wound complications; and (10) the skin may be closed in a variety of methods, but a semiocclusive dressing should be applied . As scientific evidence accumulates to refute traditional dogma, management of the surgical patient has undergone substantial changes . Surgeons should now be able to create and close an abdominal wound based upon sound scientific principles rather than simply "doing what I always do." Chembiochem, 2004 Oct 4, 5(10), 1375 - 83 Tools for glycomics: mapping interactions of carbohydrates in biological systems; Ratner DM et al.; The emerging field of glycomics has been challenged by difficulties associated with studying complex carbohydrates and glycoconjugates . Advances in the development of synthetic tools for glycobiology are poised to overcome some of these challenges and accelerate progress towards our understanding of the roles of carbohydrates in biology . Carbohydrate microarrays, fluorescent neoglycoconjugate probes, and aminoglycoside antibiotic microarrays are among the many new tools becoming available to glycobiologists. Biochem J . 2004 Sep 29; Pt {Epub ahead of print} PARP inhibition sensitizes p53-deficient breast cancer cells to doxorubicin-induced apoptosis; Munoz-Gamez JA et al.; P53 deficiency confers resistance to doxorubicin (doxo), a clinically active and widely used antitumour anthracycline antibiotic . The purpose of the current study was to investigate the reversal mechanism of doxorubicin resistance by the potent poly(ADP-ribose) polymerase (PARP) inhibitor 4-amino-1,8-naphthalimide (ANI), in the p53 deficient breast cancer cell lines EVSA-T and MDA-MB-231 . The effects of ANI, in comparison with doxo alone, on doxo-induced apoptosis, were investigated in matched pairs of EVSA-T or MDA-MB-231 with or without ANI co-treatment . Doxo elicited PARP activation as determined by western blot and immunofluorescence of poly (ADP-ribose) and ANI enhanced doxo cytotoxic activity 2.3 times and in a caspase-dependent manner . The long-term cytotoxic effect was studied by colony forming assay . Using this assay ANI also significantly potentiates the long term cytotoxic effect respect to treatment with doxo alone . Drop in mitochondrial potential together with an increase in cytochrome c release, association of Bax to the mitochondria and caspase-3 activation were also observed in the presence of ANI . Therefore, PARP inhibition may represent a novel way of selectively targeting p53 deficient breast cancer cells . The underlying mechanism is probably a potentiation of unrepaired DNA damage, shifting from DNA repair to apoptosis due to the effective inhibition of PARP activity. Am Fam Physician, 2004 Sep 15, 70(6), 1061 - 6 Asthma update: Part II . Medical management; Mintz M; The National Asthma Education and Prevention Program recently updated its guidelines for the management of asthma . An evidence-based approach was used to examine several key issues regarding appropriate medical therapy for patients with asthma . The updated guidelines have clarified these issues and should alter the way physicians prescribe asthma medications . Chronic inhaled corticosteroid use is safe in adults and children, and inhaled corticosteroids are recommended as first-line therapy in adults and children with persistent asthma, even if the disease is mild . Other medications, such as cromolyn, theophylline, and leukotriene modifiers, now are considered alternative treatments and should have a more limited role in the management of persistent asthma . The addition of a long-acting beta2 agonist to an inhaled corticosteroid is superior to all other combinations as well as to higher dosages of inhaled corticosteroids alone . Combination therapy with an inhaled corticosteroid and a long-acting beta2 agonist is the preferred treatment for adults and children with moderate to severe asthma . Antibiotic therapy offers no additional benefit in patients with asthma exacerbations. World J Urol . 2004 Sep 29; {Epub ahead of print} The technique of ultrasound guided prostate biopsy; Romics I; This article discusses the preparations for ultrasound guided prostate biopsy, the conditions used and the process of performing a biopsy . The first step in preparing the patient is a cleansing enema before biopsy . Every author proposes the use of a preoperative antibiotic based prophylaxis . Differences may be found in the type, dosage and the duration of this preoperative application, which can last from 2 h to 2 days . For anaesthesia, lidocaine has been proposed, which may be used as a gel applied in the rectum or in the form of a prostate infiltrate . Quite a few colleagues administer a brief intravenous narcosis . A major debate goes on in respect of defining the number of biopsy samples needed . Hodge proposed sextant biopsy in 1989, for which we had false negative findings in 20% of all cases . Because of this, it has recently been suggested that eight or rather ten samples be taken . There are some who question even this . Twelve biopsy samples do offer an advantage compared to six, although in the case of eight this is not the case . We shall present an in depth discussion of the various opinions on the different numbers of biopsies samples required . For the sample site, the apex, the base and the middle part are proposed, and (completing the process) two additional samples can also be taken from the transition zone (TZ), since 20% of all prostate cancers originate from TZ . In case of a palpable nodule or any lesion made visible by TRUS, an additional, targeted, biopsy has to be performed . Certain new techniques like the 3-D Doppler, contrast, intermittent and others shall also be presented . The control of the full length of samples taken by a gun, as well as the proper conservation of the samples, are parts of pathological processing and of the technical tasks . A repeated biopsy is necessary in the case of PIN atypia, beyond which the author also discusses other indications for a repeated biopsy . We may expect the occurrence of direct postoperative complications and it is necessary to know how to treat these. Int J Food Microbiol, 2004 Nov 15, 96(3), 219 - 33 Monostrain, multistrain and multispecies probiotics--A comparison of functionality and efficacy; Timmerman HM et al.; This literature review was carried out to make a comparison of functionality and efficacy between monostrain, multistrain and multispecies probiotics . A monostrain probiotic is defined as containing one strain of a certain species and consequently multistrain probiotics contain more than one strain of the same species or, at least of the same genus . Arbitrarily, the term multispecies probiotics is used for preparations containing strains that belong to one or preferentially more genera . Multispecies probiotics were superior in treating antibiotic-associated diarrhea in children . Growth performance and particularly mortality in broilers could be improved with multistrain probiotics . Mice were better protected against S . Typhimurium infection with a multistrain probiotic . A multispecies probiotic provided the best clearance of E . coli O157:H7 from lambs . Rats challenged with S . Enteritidis showed best post-challenge weight gains when treated with a multispecies probiotic . Possible mechanisms underlying the enhanced effects of probiotic mixtures are discussed . It is also emphasized that strains used in multistrain and multispecies probiotics should be compatible or, preferably, synergistic . The design and use of multistrain and multispecies probiotics should be encouraged. Am J Public Health, 2004 Oct, 94(10), 1703 - 8 Addressing externalities from swine production to reduce public health and environmental impacts; Osterberg D et al.; Animal agriculture in the United States for the most part has industrialized, with negative consequences for air and water quality and antibiotic use . We consider health and environmental impacts of current US swine production and give an overview of current federal, state, and local strategies being used to address them. Aquat Toxicol, 2004 Oct 18, 70(1), 23 - 40 Microcosm evaluation of the effects of an eight pharmaceutical mixture to the aquatic macrophytes Lemna gibba and Myriophyllum sibiricum; Brain RA et al.; Pharmaceuticals have been detected in surface waters of the US and Europe, originating largely from two sources, sewage effluent and agricultural runoff . These compounds often occur as mixtures leading to potential combined effects . In order to investigate the effects of a realistic pharmaceutical mixture on an ecosystem, a study utilizing 15 of 12,000 L aquatic microcosms treated with eight common pharmaceuticals (atorvastatin, acetaminophen, caffeine, sulfamethoxazole, carbamazepine, levofloxacin, sertraline, and trimethoprim) at total (summed) molar concentrations of 0, 0.044, 0.608, 2.664, and 24.538 micromol/L (n = 3) was conducted . Phytotoxicity was assessed on a variety of somatic and pigment endpoints in rooted (Myriophyllum sibiricum) and floating (Lemna gibba) macrophytes over a 35-day period . EC10, EC25 and EC50 values were calculated for each endpoint exhibiting a concentration-dependent response . Generally, M . sibiricum and L . gibba displayed similar sensitivity to the pharmaceutical mixture, with phytotoxic injury evident in both species, which was concentration dependent . Through single compound 7-day daily static renewal toxicity tests with L . gibba, the sulfonamide antibiotic sulfamethoxazole, the fluoroquinolone antibiotic levofloxacin and the blood lipid regulator atorvastatin were found to be the only compounds to elicit phytotoxic effects in the concentration range utilized (0-1000 microg/L) . Atorvastatin concentration was highly correlated to decreased pigment content in L . gibba, likely inhibiting the known target enzyme HMGR, the rate-limiting enzyme in isoprenoid biosynthesis . Hazard quotients were calculated for both microcosm and laboratory studies; the highest HQ values were 0.235 (L . gibba) and 0.051 (L . gibba), which are below the threshold value of 1 for chronic risks . The microcosm data suggest that at an ecological effect size of >20%, biologically significant risks are low for L . gibba and M . sibiricum exposed to similar mixtures of pharmaceutical compounds . For M . sibiricum and L . gibba, respective minimum differences of 5 and 1%, were detectable, however, these effect sizes are not considered ecologically significant. Eur J Intern Med, 2004 Aug, 15(5), 326 - 327 Roxithromycin-induced torsades de pointes; Justo D et al.; Roxithromycin is an oral macrolide antibiotic agent frequently used in the clinical setting . The risk of pro-arrhythmia during roxithromycin use has always been considered extremely remote . We describe a patient who developed prolongation of the QT interval and torsades de pointes under roxithromycin treatment. Stat Med, 2004 Oct 30, 23(20), 3227 - 40 Dependency issues in survival analyses of 55,782 primary hip replacements from 47,355 patients; Lie SA et al.; Artificial hip joints are used in only one hip for about 85 per cent of the patients and in both hips (bilateral) for about 15 per cent of the patients . The occurrence of bilateral prostheses and the influence they have in survival analyses of joint arthroplasties are seldom considered . In this study we therefore focus on issues related to bilateral primary hip prostheses, time to revision surgery, and some commonly used statistical methods . We used information from 47,355 patients with 55,782 primary hip prostheses reported to the Norwegian Arthroplasty Register between 1987 and 2000 . Due to the large number of diagnoses, fixation techniques for the prostheses, and combination of prostheses brands, we furthermore considered a 'homogeneous' subset of 8703 prostheses from 7930 patients with primary osteoarthritis, and Charnley prosthesis fixed with antibiotic-containing Palacos cement . Kaplan-Meier curves for all prostheses, ignoring that some patients have bilateral prostheses, were compared with Kaplan-Meier curves using only the first inserted prostheses, and with survival curves modified for patients with bilateral prostheses . Cox regression analyses were used to assess explanatory variables and to adjust for confounding factors . The results from the ordinary Cox regression analyses were compared with results from a marginal model, a shared gamma frailty model, and a model using a time dependent covariate to condition on failures in the opposite hip . We found no practical difference between the three calculated survival curves for the hip replacement data . The ordinary Cox-model and the marginal model gave equivalent results . In the shared gamma frailty model estimates for the risk factors were comparable with the former two approaches . The estimated frailty variance was higher when all data were used, even after adjustment for confounding factors . For the 'homogeneous' data the estimated frailty variance was negligible . Using a time dependent covariate to condition on previous revisions in the opposite hip, we found a higher risk of revision for the remaining primary hip prosthesis if the opposite hip had been revised (RR = 3.49, p < 0.0001) . There was no difference in risk for revision between right and left hip prostheses . If the time interval between the two primary operations was more than two years, for the full data, the first hip prosthesis had an increased risk of revision compared to prostheses in patients with only one prosthesis (RR = 1.25, p = 0.01) . For the 'homogeneous' data no statistically significant difference was found between unilateral and bilateral prostheses . A revision in one hip, for patients with bilateral prostheses, is a risk factor for revision of the other hip . Thus, in analyses of prostheses survival, dependencies between two hip prostheses from one patient should be considered . However, ignoring possible dependencies does not necessarily have an impact on the results on standard risk factors . Nat Struct Mol Biol, 2004 Oct, 11(10), 1008 - 14 Epub 2004 Sep 26. tRNA selection and kinetic proofreading in translation; Blanchard SC et al.; Using single-molecule methods we observed the stepwise movement of aminoacyl-tRNA (aa-tRNA) into the ribosome during selection and kinetic proofreading using single-molecule fluorescence resonance energy transfer (smFRET) . Intermediate states in the pathway of tRNA delivery were observed using antibiotics and nonhydrolyzable GTP analogs . We identified three unambiguous FRET states corresponding to initial codon recognition, GTPase-activated and fully accommodated states . The antibiotic tetracycline blocks progression of aa-tRNA from the initial codon recognition state, whereas cleavage of the sarcin-ricin loop impedes progression from the GTPase-activated state . Our data support a model in which ribosomal recognition of correct codon-anticodon pairs drives rotational movement of the incoming complex of EF-Tu-GTP-aa-tRNA toward peptidyl-tRNA during selection on the ribosome . We propose a mechanistic model of initial selection and proofreading. Evid Based Dent . 2004;5(3):67. Local tetracycline is an effective adjunct in the treatment of chronic periodontitis; Gilbert A; DATA SOURCES: Medline provided the primary data source and references lists from the identified papers were reviewed to source additional studies . STUDY SELECTION: Studies published in English prior to December 2001 were included if they were primary randomised controlled trials; were conducted in human subjects; examined the effects of local tetracycline in various forms in reducing probing depth (PD) and/or improving attachment level (AL); and they reported mean and measures of variance of PD and AL . DATA EXTRACTION AND SYNTHESIS: The methods and results section of each article were read and scored by two independent readers . Meta-analyses were performed on the basis of baseline PD, type of antibiotic used, and experimental and control regimens . A random-effects model was used to combine data . RESULTS: A total of 29 studies met the inclusion criteria and were included in the meta-analyses . The quality assessment showed the studies to be of variable quality, with many failing to report relevant information . A significant mean reduction in PD was observed when tetracycline was used as an adjunct to scaling and root planing (SRP; mean difference at 12 weeks, 0.69 mm; 95% confidence interval, 0.57-0.81; P<0.001) . Tetracycline alone did not result in a statistically significant clinical improvement compared with SRP but did perform better than placebo for people whose PD was >6 mm after 4 (P<0.001) and 8 (P=0.005) weeks . CONCLUSIONS: The meta-analyses demonstrated that statistically significant, although not clinically substantial, improvement could be achieved in cases of chronic periodontitis when local delivery of tetracycline was used as an adjunct to scaling and root planing. J Bone Joint Surg Br, 2004 Sep, 86(7), 962 - 5 Allograft bone in two-stage revision of the hip for infection . Is it safe? Ammon P, Stockley I. A two-stage procedure was carried out on 57 patients with confirmed infection in a hip replacement . Allograft bone was used in the second stage . Pathogenic organisms were identified in all patients . In stage 1, the prosthesis was removed together with infected tissue . Antibiotics were added to customised cement beads . Systemic antibiotics were not used . At the second stage, 45 of the patients had either acetabular impaction grafting, femoral impaction grafting or a combination; 12 had a massive allograft . Eight patients suffered recurrent infection (14%), in six with the original infecting organism . The risk factors for re-infection were multiple previous procedures and highly resistant organisms . We believe that systemic antibiotic therapy should be considered for these patients . Allograft bone is shown to be a useful adjunct in most infected hip replacements with considerable loss of bone stock. J Anim Sci, 2004 Sep, 82(9), 2773 - 9 Morbidity effects on productivity and profitability of stocker cattle grazing in the Southern Plains; Pinchak WE et al.; Effects of bovine respiratory disease (BRD) on stocker cattle systems are unknown under extensive rangeland environments . Three experiments were conducted to test the hypothesis that BRD-based morbidity is a major factor affecting the productivity and profitability of stocker cattle grazing Southern Plains rangelands . In Exp . 1 (658 male calves; average BW = 231 kg), 17% of the cattle were treated for BRD <8 d, 6% for 8 to 14 d, and 8% for >14 d . Morbid cattle had lower ADG than did healthy cattle (P < 0.10) . Cattle requiring 14 d of pharmaceutical therapy gained less than cattle having <14 d therapy (P < 0.01) . In Exp . 2, (279 steers and bulls; average BW = 216 kg), the ADG by steers (0.74 kg x animal(-1) x d(-1)) was greater (P < 0.05) than by bulls castrated after arrival (0.64 kg x animal(-1) x d(-1)) . Castration after arrival led to a 13.5% loss in daily gain and a 10.3% loss in season-long gain . More (P < 0.05) bulls castrated after arrival (60%) were morbid compared with steers (28%) . In Exp . 3, 633 heifers (average BW = 251 kg) were used to test the effects of morbidity on weight gain and reproduction . Heifers with lower initial weights exhibited increased (P < 0.05) morbidity . Heifers requiring two or more antibiotic treatments gained 0.03 kg/d less (P < 0.10) than did healthy heifers and had lower (P < 0.05) conception rates (66 vs . 81%) . Conception rate in twice-treated heifers was 19% less than healthy heifers . Morbid heifers conceived 0.6 mo later (P < 0.05) than healthy heifers . Under the conditions of Exp . 1 and Exp . 2, morbidity decreased net returns 9.7 to 21.3% per animal . Adjusted gross returns per animal in Exp . 3 for replacement heifers were 3 to 7.8% less for morbid heifers. Acta Medica (Hradec Kralove), 2004, 47(2), 97 - 9 Impact of processing on surface structure of human cardiac valve allografts; Krs O et al.; Methods of processing and cryopreservation are believed to be the most important factors of long term clinical performance of biological heart valve prostheses . That is why we decided to cooperate in evaluating the impact of current AHV (allograft heartvalve) bank protocol on valve tissue morphology . AHV harvested from "heart-beating" cadaveric donors, considered as a fresh tissue, were compared with valve samples from non-heart beating donors, samples stored in saline, samples treated with antibiotic solution, and finally with cryopreserved valves, stored in liquid nitrogen for months . All samples were dissected, dried with hexamethyldisilazane (HMDS) method, gold-coated, studied and photographed in scanning electron microscope Tesla BS 301 . Different superficial patterns were found on ventricular and vascular surfaces of "fresh" semilunar valves . We were able to detect early changes of endothelium after harvesting, denudation of endothelial covering during preservation with and without freezing . Our alternative method of drying samples by HMDS method proved to be suitable for thin membranes of human semilunar valves . Scanning electron microscopy seems to be helpful for morphological control of processing, cryopreservation and liquid nitrogen storage of AHV . We believe that further confrontation of morphological investigation with other methods helps us to develop more suitable protocol of handling AHV in heart valve banking. Pediatr Blood Cancer, 2004 Nov, 43(6), 698 - 702 Atypical mycobacterial infections in children with cancer; Reilly AF et al.; Atypical mycobacteria are seen more frequently as a cause of serious infection in children with cancer . Thirteen pediatric cancer patients with blood or tissue cultures positive for atypical mycobacteria were identified by review of records over a 5-year period at one center . All had central venous catheters and were lymphopenic at the time of infection . Eleven children had rapidly growing mycobacteria and two children had M . avium-intracellulare . Nine patients had positive blood cultures . Three were treated with catheter removal as sole therapy, five had catheter removal plus antibiotics, and one had antibiotics alone . Two patients with pulmonary M . avium-intracellulare infection received antibiotic therapy alone . It is concluded that infection with rapidly growing mycobacteria in children with cancer is associated with presence of a central venous catheter and lymphopenia . Some children with uncomplicated catheter-associated infection with rapidly growing mycobacteria may be sufficiently treated with removal of the catheter alone . (c) 2004 Wiley-Liss, Inc. Chemistry, 2004 Oct 25, 10(21), 5443 - 59 Vinyl sulfoxides as stereochemical controllers in intermolecular Pauson-Khand reactions: applications to the enantioselective synthesis of natural cyclopentanoids; Rodriguez Rivero M et al.; The use of sulfoxides as chiral auxiliaries in asymmetric intermolecular Pauson-Khand reactions is described . After screening a wide variety of substituents on the sulfur atom in alpha,beta-unsaturated sulfoxides, the readily available o-(N,N-dimethylamino)phenyl vinyl sulfoxide (1 i) has proved to be highly reactive with substituted terminal alkynes under N-oxide-promoted conditions (CH(3)CN, 0 degrees C) . In addition, these Pauson-Khand reactions occurred with complete regioselectivity and very high diastereoselectivity (de=86->96 %, (S,R(S)) diastereomer) . Experimental studies suggest that the high reactivity exhibited by the vinyl sulfoxide 1 i relies on the ability of the amine group to act as a soft ligand on the alkyne dicobalt complex prior to the generation of the cobaltacycle intermediate . On the other hand, both theoretical and experimental studies show that the high stereoselectivity of the process is due to the easy thermodynamic epimerization at the C(5) center in the resulting 5-sulfinyl-2-cyclopentenone adducts . When it is taken into account that the known asymmetric intermolecular Pauson-Khand reactions are limited to the use of highly reactive bicyclic alkenes, mainly norbornene and norbornadiene, this novel procedure constitutes the first asymmetric version with unstrained acyclic alkenes . As a demonstration of the synthetic interest of this sulfoxide-based methodology in the enantioselective preparation of stereochemically complex cyclopentanoids, we have developed very short and efficient syntheses of the antibiotic (-)-pentenomycin I and the (-)-aminocyclopentitol moiety of a hopane triterpenoid. Antimicrob Agents Chemother, 2004 Oct, 48(10), 3655 - 61 Telithromycin treatment of chronic Chlamydia pneumoniae infection in C57BL/6J mice; Tormakangas L et al.; Chronic Chlamydia pneumoniae infections have been associated with atherosclerosis, but clear knowledge about how these infections should be treated is lacking . We studied the effect of a new ketolide antibiotic, telithromycin, on chronic C . pneumoniae lung infection . Female C57BL/6J mice on a 0.2% cholesterol diet were inoculated intranasally with C . pneumoniae either two or three times every fourth week . Telithromycin was given to the mice subcutaneously at 75 mg/kg of body weight once daily for 5 or 10 days, starting at 3 days after the last inoculation . Samples were taken at 4 and 12 weeks after the last inoculation . The presence of C . pneumoniae DNA in lung tissue was demonstrated by PCR and the detection of lipid accumulation in the aortic sinus by Oil-Red-O staining . C . pneumoniae DNA positivity and inflammatory reactions in the lung tissue of the mice inoculated twice were significantly affected by treatment after both inoculations or only after the second inoculation at 12 weeks . Intimal lipid accumulation in the aortic sinus was also slightly but significantly less abundant in the mice treated after both inoculations compared to the levels in those treated only after the second inoculation for 10 days (geometric means, 823 and 4,324 microm(2), respectively; P = 0.033) . No differences between the infected, untreated controls and the group inoculated three times and treated for 5 days were seen . We conclude that telithromycin is effective in preventing the development of chronic C . pneumoniae infection and intimal lipid accumulation in C56BL/6J mice when the treatment is given after each inoculation. Biol Reprod . 2004 Sep 22; {Epub ahead of print} A Novel Method for the Production of Transgenic Cloned Pigs: Electroporation-Mediated Gene Transfer to Non-Cultured Cells and Subsequent Selection with Puromycin; Watanabe S et al.; Puromycin N-acetyl transferase gene (pac), whose gene product catalyzes antibiotic puromycin (an effective inhibitor of protein synthesis), has been widely used as a dominant selection marker in ES cell-mediated transgenesis . The present study is the first to report on the usefulness of puromycin for production of EGFP transgenic piglets after somatic cell cloning and embryo transfer . Somatic cells isolated from porcine fetuses at 73 days of gestation were immediately electroporated with a transgene (pCAG-EGFPac) carrying both EGFP cDNA and pac . This procedure aims to avoid aging effects thought to be generated during cell culture . The recombinant cells were selected with puromycin at a low concentration (2 micro g/ml), cultured for 7 days, and then screened for EGFP expression prior to somatic cell cloning . The manipulated embryos were transplanted into the oviducts of 14 foster mother sows . Four of the foster sows became pregnant and 9 piglets were delivered . Of the nine piglets, eight died shortly after birth and one grew healthy after weaning . Results indicate that puromycin can be used for the selection of recombinant cells from non-cultured cells, and moreover, may confer the production of genetically engineered newborns via nuclear transfer techniques in pigs. Adv Perit Dial, 2004, 20, 71 - 3 Relapsing peritonitis in continuous ambulatory peritoneal dialysis and an unconventional approach to treatment; Whaley-Connell A et al.; Relapsing peritonitis is usually attributable to persistent catheter infection, assuming that the appropriate antibiotic is used to treat each time and that intraabdominal pathology has been ruled out . Removal of the peritoneal dialysis (PD) catheter frequently is curative . We describe here a case in which partial removal of a presternal catheter resulted in resolution of relapsing peritonitis. J Econ Entomol, 2004 Aug, 97(4), 1278 - 83 Effect of cotton cultivar on development and reproduction of Aphis gossypii (Homoptera: Aphididae) and its predator Propylaea japonica (Coleoptera: Coccinellidae); Du L et al.; The effects of three cotton cultivars with low ('ZMZ13'), medium ('HZ401'), and high ('M9101') gossypol contents on the development, reproduction, and survival of Aphis gossypii Glover and its predator Propylaea japonica (Thunberg) were investigated . Developmental duration and immature survivorship did not vary between aphids on the three cultivars, whereas A . gossypii feeding on M9101 (high gossypol cultivar) displayed significantly shorter adult longevity and lower fecundity than aphids fed on 'ZMS13' and 'HZ401' . Free fatty acid content in cotton aphids reared on 'M9101' was greater than in those reared on 'HZ401' and 'ZMS13' . No significant differences in survival and lifetime fecundity of P . japonica were observed between P . japonica fed cotton aphids reared on the three different cultivars . P . japonica fed aphids from 'M9101' showed a significantly shorter developmental period and greater adult weight than those fed aphids from the other two cultivars . The decreased larval developmental duration and increased adult weight of P . japonica fed cotton aphids reared on the high gossypol-containing cultivar might have been caused by the high fatty acid content of the prey aphids . Our results indicate that high gossypol in host cotton had an antibiotic effect on A . gossypii and showed a positive effect on growth and development of P . japonica at the third trophic level . This suggests compatibility between one form of host plant resistance and biological control by predators . The allelochemical contents should be taken into account in integrated pest management for their effects on both herbivores and entomophagous insects. Sci China C Life Sci, 2004 Feb, 47(1), 66 - 73 Antitumor effects of the molecule-downsized immunoconjugate composed of lidamycin and Fab' fragment of monoclonal antibody directed against type IV collagenase; Fengqiang W et al.; Type IV collagenase plays an important role in tumor invasion and metastasis through cleaving type IV collagen in the basement membrane and extracellular matrix . In this study a molecule-downsized immunoconjugate (Fab'-LDM) was constructed by linking lidamycin (LDM), a highly potent antitumor antibiotic, to the Fab' fragment of a monoclonal antibody directed against type IV collagenase and its antitumor effect was investigated . As assayed in 10% SDS-PAGE gel, the molecular weight of Fab'-LDM conjugate was 65 kD with a 1 : 1 molecular ratio of Fab' and LDM . The Fab'-LDM conjugate maintained most part of the immunoreactivity of Fab' fragment to both type IV collagense and mouse hepatoma 22 cells by ELISA . By MTT assay, Fab'-LDM conjugate showed more potent cytotoxicity to hepatoma 22 cells than that of LDM . Administered intravenously, Fab'-LDM conjugate proved to be more effective against the growth of subcutaneously transplanted hepatoma 22 in mice than free LDM in two experiment settings . In Experiment I, the drugs were given intravenously on day 1 and day 8 . Fab'-LDM at the doses of 0.025 mg/kg, 0.05 mg/kg and 0.1 mg/kg inhibited tumor growth by 76.7%, 93.3% and 94.8%, while free LDM at 0.05 mg/kg inhibited tumor growth by 76.1%, respectively . In experiment II, the drugs were given intravenously on day 4 and day 11, Fab'-LDM at the doses of 0.025 mg/kg and 0.05 mg/kg inhibited tumor growth by 74.2%, 80.9%, while free LDM at 0.05 mg/kg inhibited tumor growth by 60.5%, respectively . In terms of survival time, Fab'-LDM was more effective than free LDM . The results suggest that the molecule-downsized immunoconjugate directed against type IV collagenase is of high efficacy in experimental cancer therapy. An Otorrinolaringol Ibero Am, 2004, 31(4), 373 - 8 {Idiopathic supraclavicle abscess with extension to the cervico-thoracic intersection}; Pino Rivero V et al.; The incidence of deep neck abscesses has clearly decreased thanks to antibiotic therapy . In most of the cases we can find an odontogenic or pharyngotonsillar cause and the infection can extend from its origin to deep cervical spaces or mediastinum . We are reporting the clinical case of a 71 year-male diagnosed as right supraclavicle and idiopatic abscess that reaches the cervico-thoracic intersection . The patient was urgently operated by drainage of the purulent collection being carried later to ICU where he suffered an adult respiratory distress syndrome (ARDS) which required a change on the treatment up to the resolution. Biochem Biophys Res Commun, 2004 Oct 22, 323(3), 979 - 86 4-Epidoxycycline: an alternative to doxycycline to control gene expression in conditional mouse models; Eger K et al.; Since the pioneering work by Gossen and Bujard in 1992 demonstrating the usefulness of the Escherichia coli derived tet resistance operon for regulating gene expression a large collection of doxycycline-controlled transgenic mice has been established . Gene switching in eukaryotic tissue culture cells or mice requires administration of tetracycline, anhydrotetracycline or doxycycline to efficiently inactivate the transactivator protein tTA (TET-OFF system) or alternatively to activate the reverse transactivator protein rtTA (TET-ON system) . However, the antibiotic activity of doxycycline can create an imbalance of the intestinal flora, resulting in diarrhoea and in a smaller number of animals in colitis . Previous studies reported that 4-epidoxycycline (4-ED), a hepatic metabolite of doxycycline, does not function as an antibiotic in mice . This gave us the idea that 4-ED might be useful for controlling gene expression in mice without the unwanted antibiotic side effect . To study the applicability of 4-ED for control of gene expression we used cell lines expressing the oncogene HER2 under control of tTA (TET-OFF) as well as rtTA (TET-ON) . 4-ED and doxycycline were similarly efficient in switching on or -off HER2 expression . In vivo we used a conditional mouse model that allows switching off HER2 in tumor tissue . We show that (i) doxycycline, 7.5mg/ml in drinking water (used as a positive control), (ii) 4-ED, 7.5mg/ml in drinking water, (iii) 4-ED, 10mg/kg body weight, s.c., and (iv) anhydrotetracycline, 10mg/kg, s.c . (used as a second positive control), were similarly efficient . Using mice with tumor volumes of 1.6cm(3) all four schedules led to a tumor remission of more than 95% within 7 days . In conclusion, 4-ED is similarly efficient as doxycycline to control gene expression in vitro and in mice . Since 4-ED lacks the antibiotic activity of doxycycline it may help to avoid adverse side effects and selection of resistant bacteria. Ann Epidemiol, 2004 Oct, 14(9), 669 - 75 Clinical pathway care improves outcomes among patients hospitalized for community-acquired pneumonia; Hauck LD et al.; PURPOSE: To examine the impact of a unique evidence-based clinical pathway on six outcomes of care in patients hospitalized for community-acquired pneumonia (CAP) . METHODS: A retrospective cohort study of CAP patients discharged between January 1999 and December 2001, from 31 Adventist Health System institutions nationwide . A total of 22,196 records were available for multivariate analyses . Odds ratios (OR) for the outcomes were calculated and stratified by a unique severity score . The severity score ranged from 1 to 5, where 5 indicated the most severe condition . RESULTS: Pathway patients were significantly less likely to die in-hospital compared with non-pathway patients in four of the five severity strata (OR in severity level 1=0.37; 95% confidence interval {CI}, 0.20-0.70) . In all severity strata, pathway patients were approximately twice as likely as non-pathway patients to receive blood cultures and appropriate antibiotic therapy . Among patients who were classified as severity level 1, pathway patients experienced an 80% reduction in the odds of respiratory failure requiring mechanical ventilation (OR=0.20; 95% CI, 0.12-0.33) . CONCLUSIONS: Patients who were placed on pneumonia clinical pathway care were much more likely than non-pathway patients to have favorable outcomes of care. Curr Drug Targets CNS Neurol Disord, 2004 Aug, 3(4), 325 - 32 The MAPK/JNK signalling pathway offers potential therapeutic targets for the prevention of acquired deafness; Zine A et al.; The c-Jun N-terminal kinases (JNKs) are also called stress activated protein kinases (SAPKs) and are members of the family of mitogen activated protein kinases (MAPKs) . While the functions of the JNKs under physiological conditions are diverse and not completely understood, there is increasing evidence that JNKs are potent effectors of apoptosis of oxidative stress-damaged cells in both the brain and the mammalian inner ear following a trauma . The activation of the inducible transcription factor c-Jun by N-terminal phosphorylation is a central event in JNK-mediated apoptosis of oxidative stress-damaged auditory hair cells following exposure to either acoustic trauma or a toxic level of an aminoglycoside antibiotic and also the apoptosis of auditory neurons as a consequence of a loss of the trophic support provided by the auditory hair cells . In this review, we summarise what is known about the expression and activation of G-proteins, JNKs, c-Jun and c-Fos under oxidative stress conditions within the mammalian cochlea . A particular focus is put on a new peptide conjugate that is a promising protective agent(s) and pharmacological strategies for preventing cochlear damage induced by both acoustic trauma and aminoglycoside ototoxic damage. Biochemistry, 2004 Sep 28, 43(38), 12297 - 305 Interaction of inhibitors of the vacuolar H(+)-ATPase with the transmembrane Vo-sector; Pali T et al.; The macrolide antibiotic concanamycin A and a designed derivative of 5-(2-indolyl)-2,4-pentadienamide (INDOL0) are potent inhibitors of vacuolar H(+)-ATPases, with IC(50) values in the low and medium nanomolar range, respectively . Interaction of these V-ATPase inhibitors with spin-labeled subunit c in the transmembrane V(o)-sector of the ATPase was studied by using the transport-active 16-kDa proteolipid analogue of subunit c from the hepatopancreas of Nephrops norvegicus . Analogous experiments were also performed with vacuolar membranes from Saccharomyces cerevisiae . Membranous preparations of the Nephrops 16-kDa proteolipid were spin-labeled either on the unique cysteine C54, with a nitroxyl maleimide, or on the functionally essential glutamate E140, with a nitroxyl analogue of dicyclohexylcarbodiimide (DCCD) . These residues were previously demonstrated to be accessible to lipid . Interaction of the inhibitors with these lipid-exposed residues was studied by using both conventional and saturation transfer EPR spectroscopy . Immobilization of the spin-labeled residues by the inhibitors was observed on both the nanosecond and microsecond time scales . The perturbation by INDOL0 was mostly greater than that by concanamycin A . Qualitatively similar but quantitatively greater effects were obtained with the same spin-label reagents and vacuolar membranes in which the Nephrops 16-kDa proteolipid was expressed in place of the native vma3p proteolipid of yeast . The spin-label immobilization corresponds to a direct interaction of the inhibitors with these intramembranous sites on the protein . A mutational analysis on transmembrane segment 4 known to give resistance to concanamycin A also gave partial resistance to INDOL0 . The results are consistent with transmembrane segments 2 and 4 of the 16-kDa putative four-helix bundle, and particularly the functionally essential protonation locus, being involved in the inhibitor binding sites . Inhibition of proton transport may also involve immobilization of the overall rotation of the proteolipid subunit assembly. Wien Klin Wochenschr, 2004 Jul 31, 116(14), 495 - 9 Comparison of the efficacy of 250 mg and 500 mg clarithromycin used with lansoprazole and amoxicillin in eradication regimens for Helicobacter pylori infection; Bago J et al.; AIMS AND METHODS: The aim of this study was to compare the efficacy of 250 mg and 500 mg clarithromycin used with lansoprazole and amoxicillin in eradication of H . pylori infection . 235 patients with H . pylori infections and non-ulcer dyspepsia were randomly assigned to one of the following regimens: lansoprazole 30 mg, amoxicillin 1000 mg, clarithromycin 250 mg (LAC250) and lansoprazole 30 mg, amoxicillin 1000 mg, clarithromycin 500 mg (LAC500) . All drugs were given twice daily for 7 days . The patients were assessed for prevalence of H . pylori with the CLO test . Gastric biopsy samples obtained during upper gastrointestinal endoscopy before randomization and 4-6 weeks after completion of therapy were used for histology and culture . Bacterial sensitivity to clarithromycin and amoxicillin was determined with the E-test . RESULTS: 101 patients in the LAC250 mg group and 102 in the LAC500 group completed the study . On intention-to-treat analysis, eradication rates were 81% with LAC250 and 82% with LAC500 (p=0.88) . On per-protocol analysis, eradication rates were 92% with LAC250 and 96% with LAC500 (p=0.23) . Among the 203 patients (86% of the entire study group) for whom H . pylori antibiotic-sensitivity testing was technically feasible, primary resistance to clarithromycin was found in 9% and to amoxicillin in 0% . Eradication of clarithromycin sensitive/resistant strains was 94%/38% for LAC250 (p < 0.001) and 93%/40% for LAC500 (p < 0.001) . CONCLUSIONS: The cure rates for the two regimens were similar, although adverse effects were more frequent with the LAC500 regimen, suggesting that 250 mg of clarithromycin b.d . may be sufficient in our patient population. Proteomics, 2004 Dec, 4(12), 3864 - 80 Activation and expression of proteins during synchronous germination of aerial spores of Streptomyces granaticolor; Bobek J et al.; Synchronously germinating aerial spores of Streptomyces granaticolor were used to study protein activation and expression during the transition from dormant to metabolically active vegetative forms . The first phase of protein activation is associated with the solubility of proteins . Three major chaperones, DnaK, Trigger factor, and GroEL, were identified in spores . Enhancement in rate of protein synthesis during germination was accompanied by the association of TF and DnaK with ribosomes . During germination, the chaperones TF, GroEL, and DnaK undergo reversible phosphorylation . GroEL was phosphorylated on both Ser and Thr, whereas phosphorylation of DnaK and TF was detected on Thr only . A proteomic approach was used to gain more information on protein expression during germination on two types of media differing in the ability of cells to produce antibiotic granaticin . To obtain an overview of the metabolic activity of germinating spores, glycolytic enzymes, enzymes of citric acid cycle, metabolism of amino acids and nucleic acids, and components of the protein synthesis system were identified and analyzed using the proteomic database . The results were deposited on the SWICZ proteomic server and are accessible on http://proteom.biomed.cas.cz. Pediatr Nephrol . 2004 Sep 17; {Epub ahead of print} Diffuse xanthogranulomatous pyelonephritis in a child with severe complications; Chen HJ et al.; Xanthogranulomatous pyelonephritis is a rare disease in childhood . Because the symptoms and signs are chronic and non-specific, preoperative diagnosis is usually difficult . We report an 8-year-old boy who had an abdominal mass and anemia for more than 6 months . Fever and dyspnea occurred 4 days prior to admission . Ultrasonography revealed an enlarged right kidney with multiple parenchymal hypoechogenic areas, absence of normal parenchymal structures, and perinephric thickening with multiple calcifications . An abdominal computed tomogram demonstrated an irregular, enlarged right kidney with multiple low-density round areas consistent with hydronephrosis and calculi . Diminished excretion of contrast media and a severe perinephric inflammatory reaction were present . Poor right kidney function was demonstrated by Tc(99m )-diethylenetriamine penta-acetic acid split renal function examination . We diagnosed xanthogranulomatous pyelonephritis preoperatively based on the clinical and radiological features . The child first had drainage of an extrarenal abscess and antibiotic therapy, followed by definitive nephrectomy . The hospital course was complicated with pleural effusion, peritonitis, pelvic abscess, and sepsis . A two-stage nephrectomy requiring less radical resection and decreasing the surgical complications would have been preferable. J Am Podiatr Med Assoc, 2004 Sep-Oct, 94(5), 492 - 8 Salvage of the first ray in a diabetic patient with osteomyelitis; Roukis TS et al.; A case report is presented of a 65-year-old diabetic woman with an 18-month history of a penetrating ulcer of the plantar aspect of the first metatarsal head with associated sepsis of the first metatarsophalangeal joint and adjacent underlying osteomyelitis . Salvage of the first metatarsophalangeal joint was performed through aggressive soft-tissue and osseous debridement, external fixation with antibiotic-loaded polymethyl methacrylate bone cement, and delayed interpositional autogenous iliac crest bone graft arthrodesis . Osseous incorporation of the interposed bone graft occurred 12 weeks postoperatively . No soft-tissue or osseous complications occurred during the postoperative period, and at 1-year follow-up there was no evidence of ulceration recurrence, transfer ulceration, shoe-fit problems, or gait abnormalities . A detailed review of the literature on the use of external fixation and interpositional bone graft distraction arthrodesis of the first metatarsophalangeal joint is presented. Immunohematol, 2004, 20(1), 63 - 6 Cefotetan-induced immune hemolytic anemia following prophylaxis for cesarean delivery; Shariatmadar S et al.; Second- and third-generation cephalosporins, notably cefotetan, are increasingly implicated in severe, sometimes fatal immunemediated hemolytic anemia . We describe a 26-year-old woman who developed severe hemolytic anemia 2 weeks after receiving a single prophylactic dose of cefotetan during cesarean delivery . The patient's DAT was weakly reactive for IgG and her serum reacted with cefotetan-coated RBCs . The antibody had a titer of 4,096 by antiglobulin testing . The patient required treatment with two units of PRBCs and experienced gradual resolution of hemolysis . Our case emphasizes the need for increased awareness of delayed onset hemolytic anemia following prophylactic use of cefotetan. MMW Fortschr Med, 2004 Jun 3, 146(23), 34 - 7 {Diagnosis and treatment of intrahepatic cholestasis syndrome}; Kraus MR et al.; Prompted by the histomorphological aspect of ductopenia, chronic intrahepatic liver diseases are increasingly being subsumed under the term vanishing bile duct syndrome . Classification by cholestasis syndromes in adults (e.g . primary biliary cirrhosis, primary sclerosing cholangitis) and in the newborn or children (e.g . alphal antitrypsin deficiency, cystic fibrosis) makes good sense . Decisive for the diagnosis are, depending on the disease presenting, a typical constellation of laboratory results, detection of autoantibodies, imaging procedures (e.g . ERC, MRI), liver biopsy where indicated, or suspected drug-induced cholestasis . Byway of treatment, ursodeoxycholic acid, an antibiotic in cholestasis, and liver transplantation in some cases, are possible options . Supportive treatment should be aimed at extrahepatic manifestations of cholestasis (e.g . osteoporosis, vitamin deficiency, pruritis). Eur J Gastroenterol Hepatol, 2004 Oct, 16(10), 987 - 90 Ranitidine-bismuth citrate, tetracycline and metronidazole followed by triple therapy as alternative strategy for Helicobacter pylori treatment: a pilot study; Calvet X et al.; BACKGROUND: Eradication rates of triple therapy--a proton pump inhibitor, clarithromycin and amoxicillin twice daily for 7 days--are suboptimal in some areas of the world . Triple therapy combining ranitidine-bismuth citrate, tetracycline and metronidazole is a very effective second-line therapy . Management strategies including this treatment as first-line therapy may represent a reasonable choice . AIM: To evaluate the efficacy of a strategy combining ranitidine-bismuth citrate triple therapy followed by a proton pump inhibitor-based triple therapy for Helicobacter pylori eradication in a pilot study . PATIENTS AND METHODS: One hundred and thirty-six consecutive H . pylori-positive patients were treated with 400 mg ranitidine-bismuth citrate twice daily, 500 mg tetracycline three times daily and 500 mg metronidazole three times daily for 7 days . Second-line therapy consisted of 20 mg omeprazole twice daily, 500 mg clarithromycin twice daily and 1 g amoxicillin twice daily for 7 days . The efficacy of the treatment was evaluated by histology or the urea breath test . RESULTS: Cure rates were 109/136 patients {80.2%; 95% confidence interval (CI), 72-86%} by intention to treat and 109/127 (85.8%; 95% CI, 78-91%) per protocol . Fifteen of the patients with treatment failure received second-line treatment . Cure rates for the strategy as a whole were 119/136 (87.5%; 95% CI, 81-92%) by intention to treat and 119/123 (96.8%; 95% CI, 92-99%) per protocol . CONCLUSIONS: The strategy achieves good eradication rates . As the first-line therapy avoids the use of clarithromycin, it could be useful in areas where high resistance to this antibiotic lead to poor results with triple therapy. Ambul Pediatr, 2004 Sep-Oct, 4(5), 455 - 60 Child care center policies and practices for management of ill children; Friedman JF et al.; OBJECTIVES: The objectives of this study were to 1) describe child care staff knowledge and beliefs regarding upper respiratory tract infections and antibiotic indications and 2) evaluate child care staff reported reasons for a) exclusion from child care, b) referral to a health care provider, and c) recommending antibiotics for an ill child . METHODS: A longitudinal study based in randomly selected child care centers in Massachusetts . Staff completed a survey to assess knowledge regarding common infections . For six weeks, staff completed a record of absences each day, describing the reason for an absence, and advice given to the parents regarding exclusion, referral to a health care provider, and obtaining antibiotics . Exclusions for the specific illness/symptom were defined as appropriate or inappropriate based on national guidelines . RESULTS: A large proportion of child care staff incorrectly believed that antibiotics are indicated for bronchitis (80.5%) and green rhinorrhea (80.5%) in children . For 82.2% of absences, the circumstances or reasons for the absence were discussed with a child care staff member . Of 538 absences due to illness that child care staff discussed with parents, there were 45 inappropriate exclusions (8.4% of illnesses discussed), 91 appropriate exclusions (16.9% of illnesses discussed), and 402 cases (74.7%) in which no recommendation for exclusion was made . CONCLUSIONS: Misconceptions regarding the need for antibiotics for URIs are common among child care staff . However, day care staff do not pressure parents to seek medical attention or antibiotics. J Med Chem, 2004 Sep 23, 47(20), 4806 - 9 A peptide nucleic acid-neamine conjugate that targets and cleaves HIV-1 TAR RNA inhibits viral replication; Riguet E et al.; The neamine part of the aminoglycoside antibiotic neomycin B was conjugated to a 16 mer peptide nucleic acid (PNA) targeting HIV-1 TAR RNA . Attachment of the neamine core allows cellular uptake of the PNA and results in potent inhibition of HIV-1 replication . The polycationic neamine moiety imparts greater solubility to the PNA and also confers a unique RNA cleavage property to the conjugate which is specific to its target site and functional at physiological concentrations of Mg(2+) . These properties suggest a potential therapeutic application for this class of compounds. Am J Med Qual, 2004 Jul-Aug, 19(4), 157 - 65 Hospital quality improvement activities and the effects of interventions on pneumonia: a multistate study of Medicare beneficiaries; Weingarten JP Jr et al.; This article evaluates the relative effectiveness of quality improvement interventions on increasing the time to antibiotic administration after a diagnosis of pneumonia . Clinical data were abstracted from the medical records of 17,040 Medicare beneficiaries discharged from one of 215 acute-care hospitals across 15 states . Thirteen Quality Improvement Organizations collected data on hospital quality improvement interventions from each hospital in this study . Medicare discharges between January 1997 and January 2002 define the study period . Most hospitals implemented multiple interventions to improve pneumonia care . Only 3 individual interventions were found to be effective in increasing time to antibiotic administration . Data feedback and benchmarking and medical records checklists had a positive effect on time to antibiotic administration . Administrative support by itself had a negative effect on the quality indicator . Although several combinations of interventions were also found effective, generalizations about the use of multiple interventions in quality improvement are difficult to make from retrospective studies. J Biomed Mater Res, 2004 Oct 15, 71B(1), 77 - 83 The in vitro elution of gentamicin sulfate from a commercially available gentamicin-loaded acrylic bone cement, VersaBond AB; Lewis G et al.; The present study was designed to yield results that would be used to contribute to the ongoing debate about the mechanism of the in vitro elution of an antibiotic from an antibiotic-loaded acrylic bone cement . To this end, the elution rates (R) of gentamicin sulfate (expressed as a weight percentage of the initial mass of the antibiotic in the specimen, normalized with respect to the duration of the test) from statically loaded (STATIC) and dynamically loaded (+/-10 MPa; 2 Hz; until fracture; DYNAMIC) specimens fabricated from a commercially available acrylic bone cement (VersaBond AB), in phosphate-buffered saline solution at 37 degrees C, were obtained with the use of a spectrophotometric method . There was evidence of microcracking in the fracture surfaces of DYNAMIC specimens, but no such evidence in the case of STATIC specimens . The surface area of the DYNAMIC specimens, during the tensile phase of the cyclical loading, was estimated to be about 3% larger than for the STATIC specimens (1742 mm(2) versus 1696 mm(2)) . The bulk porosities P of the specimens in both sets were also determined and found to not be statistically different, with P for the STATIC and DYNAMIC specimens being 8.55 +/- 0.10 and 8.88 +/- 0.18%, respectively . At the end of the test period, R was found to be 0.36 +/- 0.20 and 1.28 +/- 0.14 wt %/day for the STATIC and DYNAMIC specimens, respectively . It is suggested that the present results provide support for the postulate that the elution mechanism of gentamicin in this cement is a surface phenomenon. Ann Pharmacother, 2004 Nov, 38(11), 1863 - 7 Epub 2004 Sep 14. Possible trimethoprim/sulfamethoxazole-induced aseptic meningitis; Therrien R; OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced aseptic meningitis . CASE SUMMARY: An 18-year-old woman diagnosed with acute myeloid leukemia was admitted for a bone marrow transplant . She had already attained remission with daunorubicin, thioguanine, and high-dose cytarabine . A routine lumbar puncture performed on admission revealed an abnormally elevated leukocyte count, and meningitis was suspected . The patient had been taking TMP/SMX (trimethoprim 120 mg) twice daily on Monday, Tuesday, and Wednesday for the past 3 months; no other medication was being used . Upon examination, the patient mentioned having had headaches for the past few weeks . Since viral, bacterial, and fungal cultures were negative, a diagnosis of aseptic meningitis was made . According to the Naranjo probability scale, TMP/SMX was a possible cause of the aseptic meningitis . Eleven days after discontinuation of TMP/SMX, lumbar puncture results had returned to normal . DISCUSSION: Many drugs have been associated with aseptic meningitis . Antibiotics are often linked with aseptic meningitis, with TMP/SMX being the most frequently associated antibiotic . Many cases of TMP/SMX-induced aseptic meningitis have been reported, while few cases have been reported with trimethoprim and sulfamethoxazole given separately . CONCLUSIONS: Despite the widespread use of TMP/SMX and the years of experience we have had with the drug, it is important to remain vigilant regarding possible adverse effects, particularly aseptic meningitis. J Intern Med, 2004 Oct, 256(4), 349 - 57 Oral quinolones in hospitalized patients: an evaluation of a computerized decision support intervention; Hulgan T et al.; OBJECTIVE: To determine whether a computerized decision support system could increase the proportion of oral quinolone antibiotic orders placed for hospitalized patients . DESIGN: Prospective, interrupted time-series analysis . SETTING: University hospital in the south-eastern United States . SUBJECTS: Inpatient quinolone orders placed from 1 February 2001 to 31 January 2003 . INTERVENTION: A web-based intervention was deployed as part of an existing order entry system at a university hospital on 5 February 2002 . Based on an automated query of active medication and diet orders, some users ordering intravenous quinolones were presented with a suggestion to consider choosing an oral formulation . MAIN OUTCOME MEASURE: The proportion of inpatient quinolone orders placed for oral formulations before and after deployment of the intervention . RESULTS: There were a total of 15 194 quinolone orders during the study period, of which 8962 (59%) were for oral forms . Orders for oral quinolones increased from 4202 (56%) before the intervention to 4760 (62%) after, without a change in total orders . In the time-series analysis, there was an overall 5.6% increase (95% CI 2.8-8.4%; P < 0.001) in weekly oral quinolone orders due to the intervention, with the greatest effect on nonintensive care medical units . CONCLUSIONS: A web-based intervention was able to increase oral quinolone orders in hospitalized patients . This is one of the first studies to demonstrate a significant effect of a computerized intervention on dosing route within an antibiotic class . This model could be applied to other antibiotics or other drug classes with good oral bioavailability. Semin Thorac Cardiovasc Surg, 2004 Spring, 16(1), 77 - 80 Methods for reduction of sternal wound infection; Fynn-Thompson F et al.; Deep sternal wound infections continue to be an uncommon but potentially devastating complication of cardiac surgical procedures . Numerous risk factors have been identified but only a few can be characterized as modifiable . These risk factors and their modifications are reviewed in the following article. Kyobu Geka, 2004 Aug, 57(9), 881 - 3 {Total removal of infected pacemaker lead with cardiopulmonary bypass; report of a case}; Shioguchi S et al.; The incidence of infection after pacemaker implant has been reported to occur rarely but it's one of the severe complication . Pacemaker lead sometimes imbedded in the right atrial and ventricular wall, and it seemed to be difficult to remove the pacemaker lead by closed techniques . The optimal treatment is total removal generator and pacing lead, therefore, it is necessary to remove with cardiopulmonary bypass . Septicemia caused by infections retained pacemaker lead developed in an 87-year-old man . Following antibiotic therapy, the lead was successfully removed by cardiotomy on cardiopulmonary bypass . Total removal with cardiopulmonary bypass would be recommended. J Heart Lung Transplant, 2004 Jun, 23(6), 729 - 36 Doxycycline ameliorates ischemic and border-zone remodeling and endothelial dysfunction after myocardial infarction in rats; Camp TM et al.; BACKGROUND: Although matrix metalloproteinase (MMP) activity increases, endothelial function decreases after myocardial infarction (MI) . The antibiotic doxycycline inhibits MMP activity in vitro . The role of doxycycline-mediated MMP inhibition in endothelial function is unclear . HYPOTHESIS: Doxycycline ameliorates endothelial dysfunction, in part, by inhibiting MMP activity . METHODS: We subjected Sprague-Dawley male rats to MI by ligating the left anterior descending arteries . We subjected another group of rats to sham surgery . We administered doxycycline in drinking water (0.67 mg/ml) to both groups 2 days before surgery: the sham group underwent sham surgery and received doxycycline therapy, and the MI group underwent MI and received doxycycline therapy (n = 6 in each group) . After 4 weeks, we anesthetized rats and prepared left ventricular rings from infarcted-ischemic (I), non-infarcted near-infarcted (NI), and sham surgery hearts with and without doxycycline treatment . RESULTS: The MMP-2 activity increased significantly in I and NI hearts, and we observed a selective increase in MMP-9 activity only in I hearts, when compared with other groups (p < 0.05), measured by zymography . Cardiac inhibitor of metalloproteinase decreased only in I hearts (p < 0.05 vs other groups), measured by Western analysis, and doxycycline treatment reversed this decrease . Contractile response of rings to acetylcholine was attenuated in the I group, suggesting nitric oxide-mediated dysfunction, and was reversed by doxycycline . The response to nitroprusside was attenuated in I hearts and ameliorated by doxycycline, suggesting cardiomyocyte dysfunction . Bradykinin induced relaxation in rings from sham surgery hearts and from NI hearts, but induced paradoxic contraction in rings from I hearts . Treatment with doxycycline reversed the paradoxic contraction . CONCLUSION: Results suggest a protective action of doxycycline in the ischemic heart, possibly because of additional pharmacologic actions such as metalloproteinase inhibition. J Epidemiol Community Health, 2004 Oct, 58(10), 852 - 7 Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood; Cohet C et al.; BACKGROUND: The "hygiene hypothesis" postulates that infections during infancy may protect against asthma and atopy . There is also some evidence that antibiotic and/or paracetamol use may increase the risk of asthma . METHODS: The study measured the association between infections, and medication use early in life and the risk of asthma at age 6-7 years . It involved 1584 children who had been notified to public health services with serious infections at age 0-4 years, and 2539 children sampled from the general population . For both groups, postal questionnaires were completed by parents . RESULTS: There was little difference in the prevalence of current wheezing between the childhood infections group (prevalence = 23.5%) and the general population group (prevalence = 24.3%) . There was also little difference whether the major site of infection was gastrointestinal (prevalence = 24.1%), invasive (prevalence = 24.6%) or respiratory (prevalence = 21.1%) . However, in both groups, there were associations with antibiotic (OR = 1.78, 95% CI 1.49 to 2.14) or paracetamol (OR = 1.38, 95% CI 1.04 to 1.83) use in the first year of life or recent paracetamol use (OR = 2.10, 95% CI 1.78 to 2.49) and current wheezing . There was a weak protective effect of childhood infections in children who had not used antibiotics in the first year of life (OR = 0.78, 95% CI 0.55 to 1.10) . CONCLUSIONS: These findings are consistent with other evidence that antibiotic use early in life may increase the risk of asthma . They are also consistent with some preliminary evidence associating paracetamol use with an increased risk of asthma . Any protective effect of notifiable childhood infections was weak. J Clin Microbiol, 2004 Sep, 42(9), 4327 - 8 Evaluation of conventional castaneda and lysis centrifugation blood culture techniques for diagnosis of human brucellosis; Mantur BG et al.; We investigated the role of the lysis centrifugation blood culture technique over the conventional Castaneda technique for the diagnosis of human brucellosis . The lysis centrifugation technique has been found to be more sensitive in both acute (20% higher sensitivity; P < 0.00001) and chronic (40% higher sensitivity; P = 0.087) forms of brucellosis . The major advantage of lysis centrifugation was in the mean detection time, which was only 2.4 days in acute and 2.7 days in chronic cases, with 103 out of 110 (93.6%) and 17 out of 20 (85%) cultures from acute and chronic brucellosis, respectively, detected before the conventional culture was positive . Our results confirmed the potential usefulness of the lysis technique in diagnosis and institution of appropriate antibiotic therapy. Int J Pediatr Otorhinolaryngol, 2004 Oct, 68(10), 1315 - 25 Diagnostic accuracy and the observation option in acute otitis media: the Capital Region Otitis Project; Gurnaney H et al.; OBJECTIVE: Studies of acute otitis media indicate that deferring antibiotics in selected patients is a valid option . This study sought to determine the effects of a multifaceted educational intervention on disease management and treatment attitudes in practitioners caring for acute otitis media (AOM) . METHODS: An expert committee composed of clinical and public health practitioners was convened which reviewed current evidence-based literature on diagnosis and treatment of AOM . A survey instrument to measure attitudes was fashioned and administered to 150 invited practitioners before and after a daylong educational intervention . The intervention was composed of two diagnostic otoscopy workshops; a lecture on an antibiotic-centered approach to treatment, followed by a lecture on the Dutch "observation without antibiotic option" (OWAO), which in 1998 involved withholding antibiotic prescription for selected patients over the age of 2 for up to 72 h; and a concluding "Miller Interactive Process"--small group sessions on five key clinical management questions . RESULTS: Significant short-term changes occurred in practitioners' attitudes in importance of ear pulling as a diagnostic symptom (P = 0.034) and clinical findings in the tympanic membrane for the diagnosis of AOM (P = 0.006) . Significant changes towards increased comfort of practitioners' management attitudes were found in managing selected patients without antibiotics (P = 0.057), using shortened courses of antibiotics (P = 0.001), and using high dose amoxicillin (80 mg/kg/day) as a second line drug (P = 0.001) . CONCLUSIONS: Practitioners' attitudes about managing AOM can be modified in the short-term with an educational intervention combining didactic, hands-on, and interactive learning that incorporates evidence-based medicine. Pathophysiology, 2004 Oct, 11(2), 95 - 101 Calcification in coronary artery disease can be reversed by EDTA-tetracycline long-term chemotherapy; Maniscalco BS et al.; Atherosclerosis is a complex process with multiple mechanisms and factors contributing to its initiation and progression . Detection and quantification of coronary artery calcium (CAC) scores with electron beam tomography has been shown to correlate with obstructive and nonobstructive coronary artery disease (CAD) . Pathogen-triggered calcification could play a role in CAD . Recent reports suggest that infectious blood nanobacteria (NB) emerge to be such a trigger . So far, minimal or no reversal of atherosclerosis has been claimed by therapies with iv ethylenediaminetetraacetic acid disodium salt (EDTA), antibiotics, or other regimens, and therapies for atherosclerosis remain non-curative . We have now combined EDTA with antibiotic tetracycline (comET), an in vitro proven nanobacteriocidal treatment, and tested comET therapy in patients with documented CAD . Three hypotheses were probed: (1) Are NB present in patients with CAD?; (2) Does treatment with comET affect blood NB antigen and serology?; (3) Does a comET decrease CAC scores? One hundred patients with stable CAD and positive CAC scores were enrolled into a 4 month study of comET therapy . ComET therapy is composed of (1) Nutraceutical Powder (Vitamin C, Vitamin B6, Niacin, Folic Acid, Selenium, EDTA, l-Arginine, l-Lysine, l-Ornithine, Bromelain, Trypsin, CoQ10, Grapeseed Extract, Hawthorn Berry, Papain) 5cm(3) taken orally every evening; (2) Tetracycline HCl 500mg taken orally every evening; (3) EDTA 1500mg taken in a rectal suppository base every evening . CAC scoring was repeated at 4 months and serum samples were analyzed for NB antigen and serology at baseline, 2 and 4 months . Complete blood count, metabolic panel, liver function, C-reactive protein (hs-CRP) and lipids were analyzed at baseline and 4 months . Seventy-seven patients completed the study and all patients were positive for NB serology, antigen or both . Responders (n = 44; 57%) had significant decreases in total CAC scores (P = 0.001), the average decrease being 14% . Non-responders (n = 33; 44%) had no change or had increases in CAC scores . Angina was decreased or ablated in 16 of 19 patients (84%) . Lipid profiles improved to non-atherogenic direction significantly (P = 0.001), a remarkable finding in a patient group where 86% were on continuous statin medication already before the trial . No adverse physiologic effects were seen in renal, hepatic, or hematopoetic systems . In conclusion, CAC scores decreased during ComET therapy trial in most CAD patients inferring regression of calcified coronary artery plaque volume . The patients tolerated the therapy well and their angina and lipid profiles improved . Further treatment trials for long term therapy with matched controls are warranted. Pediatr Infect Dis J, 2004 Sep, 23(9), 834 - 8 Comparison of five-day cefdinir treatment with ten-day low dose amoxicillin/clavulanate treatment for acute otitis media; Block SL et al.; BACKGROUND: Short course beta-lactam antibiotic therapy for acute otitis media (AOM) should improve patient adherence, but it has not been evaluated since the heptavalent pneumococcal conjugate vaccine became routinely used in the United States . METHODS: In a prospective, investigator-blinded, multicenter study, 425 patients, age 6 months-6 years, with a clinical diagnosis of nonrefractory AOM were randomized to receive either 5 days of cefdinir therapy (14 mg/kg divided twice daily) or 10 days of amoxicillin/clavulanate therapy (45/6.4 mg/kg divided twice daily) . Clinical response was assessed at end of therapy (2-4 days postantibiotic, respectively) and week 4 (study days 25-28) . RESULTS: With no difference in demographics between treatment groups, overall the mean age (+/-SD) was 2.8 +/- 1.8 years, 65% had received conjugated pneumococcal vaccination and 48% had bilateral AOM . The satisfactory clinical response rate at end of therapy was comparable for cefdinir versus amoxicillin/clavulanate (88%, 170 of 194 versus 85%, 164 of 192; 95% CI -4.9, 9.3) . Although this must be interpreted with caution, cefdinir showed an apparent trend for higher efficacy than amoxicillin/clavulanate (92%, 72 of 78 versus 77%, 55 of 71; P = 0.019) in a subsample of patients 6-24 months old who had received conjugated pneumococcal vaccination . The incidence of drug-related adverse events was less for cefdinir than for amoxicillin/clavulanate (24%, 50 of 211 versus 38%, 82 of 214; P = 0.0018) CONCLUSION: For children with nonrefractory AOM, based only on clinical endpoints, 5 days of therapy with cefdinir 14 mg/kg divided twice daily was comparable overall with 10 days of therapy with low dose amoxicillin/clavulanate 45/6.4 mg/kg divided twice daily. Biophys J, 2004 Dec, 87(6), 3814 - 25 Epub 2004 Dec. Electrostatic mechanisms underlie neomycin block of the cardiac ryanodine receptor channel (RyR2); Mead FC et al.; Neomycin is a large, positively charged, aminoglycoside antibiotic that has previously been shown to induce a voltage-dependent substate block in the cardiac isoform of the ryanodine receptor (RyR2) . It was proposed that block involved an electrostatic interaction between neomycin and putative regions of negative charge in both the cytosolic and luminal mouths of the pore . In this study, we have attempted to screen charge by increasing potassium concentration in single-channel experiments . Neomycin block is apparent at both cytosolic and luminal faces of the channel in all K+ concentrations tested and alterations in K+ concentration have no effect on the amplitudes of the neomycin-induced substates . However, the kinetics of both cytosolic and luminal block are sensitive to changes in K+ concentration . In both cases increasing the K+ concentration leads to an increase in dissociation constant (KD) . Underlying these changes are marked increases in rates of dissociation (k(off)), with little change in rates of association (k(on)) . The increase in k(off) is more marked at the luminal face of the channel . Changes in K+ concentration also result in alterations in the voltage dependence of block . We have interpreted these data as supporting the proposal that neomycin block of RyR2 involves electrostatic interactions with the polycation forming a poorly fitting "plug" in the mouths of the conduction pathway . These observations emphasize the usefulness of neomycin as a probe for regions of charge in both the cytosolic and luminal mouths of the RyR2 pore. Medinfo . 2004;2004(CD):1576. Developing Criteria-based, Context Specific Antibiograms for Hospitalized Patient Populations; Doherty JA et al.; Hospitals routinely use antibiogram reports to help clinicians select effective empiric antibiotic therapy . These reports are typically generated using data from the entire hospital and do not always reflect susceptibility profiles in subsets of the patient population . Our goal was to create an antibiogram that could be customized according to specific criteria and determine whether this would be potentially useful for assisting with initial antibiotic selection . Prior research has shown that computer decision support can significantly improve empiric antibiotic selection1. J Pediatr Surg, 2004 Sep, 39(9), 1316 - 20 Ultrasound-based decision making in the treatment of acute appendicitis in children; Kaneko K et al.; BACKGROUND/PURPOSE: Imaging techniques are used widely to diagnose appendicitis . However, the negative appendectomy rate remains at about 15% . The authors assessed ultrasound-based decision making in the treatment of acute appendicitis in children . METHODS: The authors prospectively studied 165 consecutive children (3 to 15 years old) evaluated for appendicitis . Diagnosis and treatment were based solely on ultrasound scan findings . Criterion for appendicitis was a diameter exceeding 6 mm . Severity was classified into 4 grades based on the appearance of intramural appendiceal structure . Patients with grades I or II received antibiotic therapy . Patients with grades III or IV underwent appendectomy . RESULTS: Ultrasound scan diagnosed appendicitis in 93 children (grade I, 7; grade II, 17; grade III, 41; and grade IV, 28) . All but 2 patients with grades I or II underwent antibiotic therapy without complication . All grades III or IV patients underwent appendectomy . There was no negative appendectomy among 76 appendectomies during this period . Ultrasound-based prediction of severity was correct in 67 cases (88%) . Ultrasonography identified other pathology in 39 . CONCLUSIONS: Ultrasonography in children cannot only visualize all inflamed appendices but also predict severity of disease . Treatment based entirely on ultrasound scan identified patients who required surgery for severe appendicitis and permitted successful conservative treatment for mild appendicitis. Eur Respir J, 2004 Sep, 24(3), 466 - 70 Penetration of newer quinolones in the empyema fluid; Liapakis IE et al.; The degree of penetration of newer quinolones into the pleural fluid has not been studied . The objective of the present study was to determine the degree to which moxifloxacin and levofloxacin penetrate into empyemic pleural fluid using a new rabbit model of empyema . An empyema was created via the intrapleural injection of turpentine (1 mL), followed 24 h later by instillation of 2 mL (1 x 10(10)) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits . After an empyema was verified by thoracentesis and pleural fluid analysis, moxifloxacin and levofloxacin (25 mg.kg(-1) for both, i.v.) were administered . Antibiotic levels were determined in samples of pleural fluid and in blood collected serially over 12 h . Antibiotic levels were measured using HPLC . Each of the antibiotics penetrated well into the empyemic pleural fluid . Antibiotic penetration was the greatest for moxifloxacin (area under the curve (AUC) for pleural fluid/blood (AUCPF/AUCblood) ratio=1.37) followed by levofloxacin (ratio=1.13) . The time to equilibration between the pleural fluid and blood antibiotic levels was more rapid for moxifloxacin (3.9 h) than for levofloxacin (4.4 h) . With moxifloxacin, the peak pleural fluid concentration (Cmax,PF) was 2.77 microg.mL(-1) and occurred at a time to maximum pleural fluid concentration (Tmax,PF) of 6 h after infusion and decreased thereafter . The peak blood concentration (Cmax,blood) was 4.81 microg.mL(-1) at 1 h after administration . With levofloxacin, the peak pleural fluid level (Cmax,PF=1.39 microg.mL(-1)) occurred at 6 h (Tmax,PF=6 h) after infusion . The Cmax,blood was 1.88 microg.mL(-1) at 1 h after administration . In conclusion, differences were found in the degree of penetration of the two quinolones into infected pleural fluid in rabbits . The clinical significance of these differences is unknown . More studies are needed to evaluate the pharmacokinetic parameters in the pleural space in humans. Crit Care Nurs Clin North Am, 2004 Sep, 16(3), 293 - 310, vii Pharmacologic therapy for acute exacerbations of chronic obstructive pulmonary disease: a review; Hockman RH; This article reviews available data on the drug therapy armamentarium for the acute exacerbation of chronic obstructive pulmonary disease (COPD) . Summaries of studies and therapeutic issues for bronchodilators, antibiotic therapy, corticosteroid use, and a few miscellaneous agents are presented . Many controversies exist in the criteria defining the acute exacerbation, in defining appropriate outcome parameters for assessment, and, consequently, in developing specific consistent recommendations for drug therapy . Five published guidelines assist the clinician in therapeutic drug management of the acute exacerbation of COPD, and each differs in its recommendations for drug therapy prescription . The article includes synopses for drug therapy recommendations from the guidelines. Drugs R D, 2004, 5(5), 293 - 6 Bleomycin--electrical pulse delivery: electroporation therapy-bleomycin--Genetronics; MedPulser-bleomycin--Genetronics; Probiotics and human health: a clinical perspective; Primary Industries Research Victoria, Department of Primary Industries, 600 Sneydes Road, Werribee, Victoria, Australia . harsharn.gill@dpi.vic.gov.au There is unequivocal evidence that administration of probiotics could be effective in the treatment of acute infectious diarrhoea in children and the prevention of antibiotic associated diarrhoea and nosocomial/community acquired diarrhoea . Encouraging evidence is also emerging for the effectiveness of probiotics in the prevention and management of pouchitis and paediatric atopic diseases, and the prevention of postoperative infections . There is also strong evidence that certain probiotic strains are able to enhance immune function, especially in subjects with less than adequate immune function such as the elderly . Efficacy of probiotics in the prevention of traveller's diarrhoea, sepsis associated with severe acute pancreatitis, and cancers, the management of ulcerative colitis, and lowering of blood cholesterol remains unproven . In addition to firm evidence of efficacy (for a range of conditions), major gaps exist in our knowledge regarding the mechanisms by which probiotics modulate various physiological functions and the optimum dose, frequency, and duration of treatment for different probiotic strains. Org Lett, 2004 Sep 16, 6(19), 3401 - 4 Stereoselective synthesis of the gamma-lactam hydrolysate of the thiopeptide cyclothiazomycin; Bagley MC et al.; {reaction: see text} Bohlmann-Rahtz pyridine synthesis of a chiral nonracemic enamine and thiazolylpropynone gives a terminal-protected pyridine-containing gamma-amino acid in high optical purity in a sequential one-pot multicomponent reaction that proceeds with total control of regiochemistry and with minimal racemization . Further elaboration has established the synthesis of the gamma-lactam acidic hydrolysate of the macrocyclic thiopeptide antibiotic cyclothiazomycin, a selective renin inhibitor, in only four steps and 30% overall yield and has confirmed its structure. Ann Vasc Surg, 2004 May, 18(3), 372 - 5 Successful treatment of infected vascular prosthetic grafts in the groin using conservative therapy with povidone-iodine solution; Voboril R et al.; Four cases of infected vascular prosthetic graft in the groin successfully treated with povidone-iodine solution using a conservative approach are described here . In all patients the same technique was used . After complete debridement, the prosthetic graft in the groin was completely exposed . The wound was cleansed with hydrogen peroxide and then dressed with gauze soaked in 1:10 sterile water-diluted povidone-iodine solution . The dressings were changed twice a day . The patients were supplemented by systemic therapy of an appropriate antibiotic . All patients were observed in the intensive care unit . In all patients this treatment method led to control of infection and healing of the wound . Thus, it was not necessary to remove the prosthetic graft and patients were spared a major surgical intervention . At follow-up, the prosthetic grafts remain patent without any signs of recurrence of infection. Surg Infect (Larchmt), 2004 Summer, 5(2), 145 - 59 Causes and consequences of fever complicating critical surgical illness; Barie PS et al.; BACKGROUND: Fever may have malign consequences in the postoperative period . This study was performed to determine the causes and consequences of fever in critically ill surgical patients . The specific hypothesis tested is that postoperative fever is associated with adverse clinical outcomes, including increased organ dysfunction and risk of death . METHODS: Inception-cohort study of critically ill surgical patients who manifested a core temperature of >/=38.2 degrees C for the first time . The episode of fever was monitored until resolution, which was defined as a core temperature of <38.2 degrees C for at least 72 consecutive h . Demographic data collected included age, gender, admission diagnosis, admission status (elective/emergency), severity of illness (APACHE III), the systemic inflammatory response syndrome (SIRS) score, the cumulative multiple organ dysfunction score, cause of fever (infectious/non-infectious), ICU and hospital length of stay, and mortality . The day of onset of fever in the ICU, peak temperature, ICU day of peak temperature, and duration of fever episode were recorded . All diagnostic and therapeutic interventions were recorded, including the type and duration of antibiotic therapy . Univariate results of possible significance (alpha < 0.15) were tested in logistic regression models for independence of effect upon mortality after auto-correlation was excluded by matrix correlations and the Durbin-Watson statistic . Cases where both non-infectious and infectious causes of fever were present were analyzed as part of the infectious group, whereas the cumulative MOD score was dichotomized (< 5, >/=5 points) at a value known to be associated with increased mortality . RESULTS: Among 2,419 screened patients, 626 patients (26%) developed fever . Febrile patients were older, sicker, more likely to have undergone emergency surgery, more likely to develop organ dysfunction, and more likely to die (all, p < 0.0001) . The mean day of onset of fever was day 1 and the mean peak temperature for the episode was 39.1 +/- 0.1 degrees C . For most patients, it was their only episode of fever, with a mean of 1.4 +/- 0.1 episodes/patient . Forty-six percent of febrile patients were found to have an infectious cause of fever . Nearly all patients had SIRS, and nearly all developed organ dysfunction to some degree . By logistic regression, the presence of SIRS (as opposed to fever in isolation), emergency status, higher APACHE III score and the peak temperature were associated with increased mortality, with peak temperature being the most powerful predictor in the model (OR 2.20, 95% Cl 1.57-3.19) . Gender had no bearing on outcome, and there was a trend toward a protective effect from an infectious etiology of fever . CONCLUSIONS: Postoperative fever is deleterious to critically ill patients . The magnitude of fever is a determinant of mortality, whereas an infectious etiology of fever may not be . The impacts of nosocomial infection and suppression of fever on critically surgical patients deserve further study. Hautarzt, 2004 Oct, 55(10), 987 - 9 {Sensitivity to constituents of bone cement in a patient with joint prosthesis}; Richter-Hintz D et al.; Failure to tolerate prosthetic material can lead to a variety of clinical findings . A 55-year-old woman had a total replacement of the right knee . Two weeks later she developed pruritic skin lesions over the joint, as well as pain and impaired function . Allergic testing showed clinically relevant Type IV sensitization to methylmethacrylate, as well as to various formulations of the bone cement, including one with an added antibiotic . The symptom complex of pruritic skin lesions in the area of the prosthesis, pain and disability, as well as relevant Type IV sensitization justified replacing the prosthesis. Anal Biochem, 2004 Oct 1, 333(1), 27 - 38 High-performance liquid chromatography-based methods of enzymatic analysis: electron transport chain activity in mitochondria from human skeletal muscle; Ritov VB et al.; This study addresses an application of pyridine nucleotide enzymatic analyses to evaluate the activity of the mitochondrial electron transport chain (reduced nicotinamide adenine dinucleotide (NADH) oxidase) and Complexes I and II in samples of human muscle as small as approximately 10 mg wet weight . Key aspects in this adaptation are the use of high-performance liquid chromatography with fluorescence detection of NADH and use of alamethicin, a channel-forming antibiotic that enables an unrestricted access of substrates into the mitochondrial matrix . The procedure includes disintegration of tissue by Polytron homogenizer, extraction of myosin from myofibrillar fragments by KCl/pyrophosphate to facilitate release of mitochondria, and preparation of fractions of subsarcolemmal and intermyofibrillar mitochondria . Oxidation of NADH or succinate is assayed in the presence of 40 microg/ml alamethicin and the reaction is terminated by H(2)SO(4), which also destroys the remaining NADH . Nicotinamide adenine dinucleotide (NAD) or fumarate concentrations are measured using alcohol dehydrogenase or fumarase plus malic dehydrogenase reactions, respectively . Generation of NADH, assessed in auxiliary reactions in the presence of hydrazine, is strictly proportional to NAD or fumarate content across a concentration range of 1-20 microM . NADH is quantitatively analyzed with a detection limit of 3-5 pmol by HPLC using a reverse-phase Hypersil ODS column connected to a fluorescence detector. Biochemistry, 2004 Sep 14, 43(36), 11567 - 75 Assembly and stability of nisin-lipid II pores; Hasper HE et al.; The peptide antibiotic nisin was the first reported example of an antibiotic that kills bacteria via targeted pore formation . The specific target of nisin is Lipid II, an essential intermediate in the bacterial cell-wall synthesis . High-affinity binding of the antibiotic to Lipid II is followed by rapid permeabilization of the membrane . Here, we investigated the assembly and stability of nisin-Lipid II pore complexes by means of pyrene fluorescence and circular dichroism . We demonstrated that nisin uses all available Lipid II molecules in the membrane to form pore complexes . The pore complexes have a uniform structure and consist of 8 nisin and 4 Lipid II molecules . Moreover, the pores displayed a remarkable stability, because they were able to resist the solubilization of the membrane environment by mild detergents . Similar experiments with {N20P/M21P}nisin showed that the hinge region is essential for the assembly into stable pore complexes . The new insights were used to propose a refined model for nisin pore formation. Rev Port Cir Cardiotorac Vasc, 2004 Apr-Jun, 11(2), 101 - 5 {The use of superficial femoral veins in reconstructive surgery of aortic prosthesis infection (Clagett's operation)}; da Gama AD et al.; Prosthetic aortic infection still represents an enormous challenge to the possibilities of contemporary reconstructive vascular surgery, particularly in terms of diagnosis and surgical management, and is accompanied by high mortality and morbidity rates . Several surgical methods have been devised and employed, including the extra-anatomic bypasses and the in "situ" revascularization . The later uses either antibiotic bounded prosthesis, or biologic homologous conduits, including cryopreserved allografts or autologous arteries and veins . The authors report the clinical condition of a 73 years old male with an infected aortic prosthesis, who underwent the complete removal of the infected graft, followed by an interposition of a venous autograft composed by two superficial femoral veins, removed from both thighs (Clagett's operation) . The procedure was extremely well succeeded and the patient was discharged one month later . Reviewed one year later he was found in good condition and free of symptoms. J Mater Sci Mater Med, 1997, 8(11), 667 - 74 Heterocyclic methacrylates for clinical applications-further studies of water sorption; Sawtell RM et al.; The room temperature polymerizing system comprising poly(ethyl methacrylate)-tetra hydrofurfuryl methacrylate (PEM/THFMA) has potential in orthopaedic and dental applications, and earlier work has shown it to have unusual water absorption characteristics . This aspect has been studied in further detail, by studying the water absorption behaviour from some biological solutions, and the effect of the addition of an antibiotic (gentamicin) . For comparison purposes, a parallel system whereby tetrahydrofuryl methacrylate was replaced by hydroxyethyl methacrylate (PEM/HEMA), was studied . In the case of PEM/THFMA, water uptake was substantially reduced when absorption was carried out from solutions (from about 30% in water to about 1.5% in solutions of higher concentrations), and the corresponding diffusion coefficient increased (by a factor of several hundred) . The addition of gentamicin increased uptake, but the extent of increase also decreased in solutions . It was concluded that uptake was related to the osmolarity of the external solution, and also on the presence of osmotic sites within the polymer; hence the uptake process appears to be governed by chemical potential considerations . At the higher uptakes, there was evidence of water clusters . In marked contrast, the uptake by the PEM/HEMA system was independent of the osmolarity of the external solutions, presumably due to the hydrophi