Antibiotics

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 hydrophilic nature of HEMA.

J Biol Chem, 2004 Nov 12, 279(46), 48449 - 56 Epub 2004 Sep 03.
Characterization of a novel interaction between the secretory Na+-K+-Cl- cotransporter and the chaperone hsp90; Simard CF et al.; The first isoform of the Na(+)-K(+)-Cl(-) cotransporter (NKCC1) is of central importance for the control of cellular ion concentration and epithelium-mediated salt secretion . Several studies have established that a change in intracellular {Cl(-)} (Cl(-)(i)) represents a key signaling mechanism by which NKCC1-induced Cl(-) movement is autoregulated and by which Cl(-) entry and exit on opposite sides of polarized cells are coordinated . Although this signaling mechanism is coupled to a pathway that leads to post-translational modification of the carrier, no unifying model currently accounts for the ion dependence of NKCC1 regulation . In this paper, evidence is presented for the first time that hsp90 associates with the cytosolic C terminus of NKCC1, probably when the carrier is predominantly in its unfolded form during early biogenesis . Evidence is also presented that the Cl(-)(i)-dependent regulatory pathway can be activated by a thermal stress but that it is no longer operational if NKCC1-expressing cells are pretreated with geldanamycin, an antibiotic that inhibits hsp90, albeit nonspecifically . Taken together, our data indicate that binding of hsp90 to NKCC1 may be required for Na(+)-K(+)-Cl(-) cotransport to occur at the cell surface and that it could play an important role in ion-dependent signaling mechanisms, insofar as the maneuvers that were used to alter the expression or activity of the chaperone do not exert their main effect by inducing other cellular events such as the unfolded protein response . Further studies will be required to elucidate the functional relevance of this novel interaction.

Neurosurg Focus . 2003 Sep 15;15(3):E15.
Is spinal instrumentation a risk factor for late-onset infection in cases of distant infection or surgery? Case report; Naderi S et al.; As a cause of revision spinal surgery, spinal epidural abscess after instrumentation-assisted fusion is rare in neurosurgical practice . Postoperative infections are frequently seen in the time period soon after surgery . The authors report on the case of a 45-year-old woman who had undergone posterior instrumentation-augmented fusion for L4-5 degenerative spondylolisthesis . Ten months after the operation she presented to the neurosurgery clinic with complaints of severe low-back pain and radicular right lower-extremity pain . She had undergone laparoscopic surgery for acute cholecystitis 1 month prior to readmission . Radiological study revealed a spinal epidural abscess in communication with a right psoas abscess at L4-5 . The abscess was drained percutaneously with the aid of C-arm fluoroscopic guidance, and a 6-week course of parenteral antibiotic therapy was administered . Retrograde lymphatic bacterial translocation, hematopoietic spread, and the suitable characteristics in the host may facilitate the development of infection around the implant . Thus, distant surgery and infection may be a risk factor in cases in which spinal instrumentation is placed . In such cases a prolonged antibiotic therapy for distant infection after surgery is recommended.

Neurosurg Focus . 2003 Sep 15;15(3):E14.
Postoperative wound infections of the spine; Beiner JM et al.; Postoperative spinal wound infections occur in 1 to 12% of patients . The rate of infection is related to the type and duration of the procedure, comorbidities, nutritional status, and various other risk factors . Antibiotic prophylactic therapy has been clearly shown to decrease the rate of infection dramatically after lumbar surgery . These infections typically manifest with signs and symptoms of wound swelling, erythema, and drainage . Laboratory-detected values such as the erythrocyte sedimentation rate and C-reactive protein can be elevated beyond what is normal for the uncomplicated postoperative course following lumbar surgery, and combined with the clinical symptoms should alert the physician to the possibility of infection . When detected, these infections should be managed aggressively with operative debridment and irrigation, including the deep subfascial layer in all cases except those with clearly demarcated superficial infection . The choice of one versus multiple debridments can be made based on the appearance of the wound, patient factors, and nutritional status . Hardware and incorporated bone graft can be left in place in the majority of cases, adding to stability . Outcomes following aggressive treatment of this complication can be excellent, with no long-term loss of function and complete eradication of the infection.

J Craniofac Surg, 2004 Sep, 15(5), 752 - 7
In vitro analysis of the elution of tobramycin from a calcium sulfate bone void filler; Pietrzak WS et al.; The use of synthetic calcium-based bone replacements has a recent history in craniofacial surgery as a non- to minimally load-bearing graft substitute . Given its avascular nature at the time of placement, infection is an ever present risk . Antibiotics are often added to the material during surgery based on an empirical impression . Whether effective antibiotic release actually occurs and over what time are not known for many of the available calcium-based preparations . The purpose of this study was to investigate the release kinetics of tobramycin from molded cylinders of Calcigen S bone void filler (Biomet, Warsaw, IN) and to compare this with the release kinetics of tobramycin from plaster of Paris-based systems as reported in the literature . Calcigen S bone void filler is a form of calcium sulfate that is closely related to plaster of Paris yet remains distinct . In vitro studies as well as clinical series have demonstrated that plaster of Paris is an effective vehicle to deliver tobramycin in which therapeutic doses of the antibiotic are released after implantation . In vitro analysis of the elution of tobramycin from Calcigen S bone void filler substrate is similar to that of plaster of Paris.

Ann Fr Anesth Reanim, 2004 Aug, 23(8), 794 - 8
{French residents in anaesthesia and critical care - a nationwide survey}; Gautier JF et al.; OBJECTIVE: We surveyed the residents in their first (R1) and fourth (R4, last) years of residency in anaesthesia and intensive care in France . METHODS: The questionnaires mailed to each resident were designed to obtain personal data, motivation for specializing in anaesthesia and their opinion of their training . RESULTS: The response rates were 48% for the R1 residents and 77% for the R4 residents . There were 40% females in this population and the R1 residents were 25 +/- 1 year old, 29 +/- 2 year-old for the R4 residents . Almost half (46%) of the R1 responders were married as were 74% of the R4 residents . They spent an average of 726 each year on books, computers and other educational items . Most (71%) had opted for anaesthesia after considering other medical specialties, but only 12% had considered surgery . Half (51%) were on a training program that was far away from their home . They thought highly of their training, with the clinical training being rated above the non-clinical component . About half of them had obtained specialized certificates (mainly additional certification in intensive care and antibiotic therapy) during their residency . Two thirds of those in R4 expected to work in a public hospital and about one third expected to work in intensive care . Money was an important factor in their choice of profession . A majority planned to remain in the area where they had graduated in anaesthesia after their residency . Finally, 96% declared that they would choose anaesthesia again if they had to do so . CONCLUSION: French residents in anaesthesia are satisfied of their initial choice for anaesthesia and don't regret it at the end of their residency training.

J Arthroplasty, 2004 Sep, 19(6), 760 - 7
Spacer endoprosthesis for the treatment of infected total hip arthroplasty; Durbhakula SM et al.; We reviewed the treatment of infected total hip arthroplasty with a temporary spacer endoprosthesis . To fabricate the spacer, antibiotic-loaded cement was inserted into a specially designed mold . A central rod pin was superficially imbedded as an endoskeleton once the cement reached a doughy state . After polymerization, the final product was removed from the mold and inserted as an articulating spacer . Twenty patients were followed for an average of 38 months (range, 26-67 months) . There were no recurrent or persistent infections . Eighteen patients underwent a successful 2-stage exchange . Two patients retained the spacer as a definitive treatment method . Complications with the spacer included 2 fractures and 2 dislocations . Overall, this cost-effective technique provided efficient local antibiotic delivery, early mobilization, facilitation of reimplantation, and improved patient satisfaction.

Klin Monatsbl Augenheilkd, 2004 Aug, 221(8), 677 - 82
{Vaccination for stab and bite injuries in the facial region}; Wilhelm L et al.; In cases of stab and bite injuries to the face there is a risk of general infection and the necessity for an active and/or passive immunization must be considered by the first treating physician . In Central Europe tetanus, rabies, hepatitis B and C as well as HIV must be taken into account as possible consequences of such injuries . With regard to a tetanus immunization the indication for the post-exposition prophylaxis (PEP) should generally be as wide as possible . For other protective vaccinations a differentiated decision in co-operation with other fields of activity and public health authorities should be realized . The current recommendations for the systemic infections relevant in Central Europe are described.

Biochim Biophys Acta, 2004 Sep 6, 1674(1), 60 - 7
Evidence for differences in the metabolism of saxitoxin and C1+2 toxins in the freshwater cyanobacterium Cylindrospermopsis raciborskii T3; Pomati F et al.; The activity of paralytic shellfish poisoning (PSP) toxins biosynthetic enzymes was assayed in the cyanobacterium Cylindrospermopsis raciborskii T3 after inhibiting protein synthesis with chloramphenicol (CAM) . The production of C1+2 and saxitoxin (STX) was sensitive to CAM with STX levels decreasing by 70% after 24-h exposure to the antibiotic . PSP toxin production was strongly promoted by arginine supplementation, with a maximum 476% increase in intracellular STX concentrations after 24-h exposure to 10 mM of the amino acid . However, arginine had no stimulating effect on PSP toxin levels if supplemented in combination with CAM at 10 microg l(-1) . Addition of agmatine and proline to C . raciborskii T3 cultures in the presence of 10 microg l(-1) CAM increased C1+2 toxins levels, while having a negative or no effect on STX accumulation . In vitro, PSP toxin levels increased naturally in cyanobacterial extracts, with CAM and arginine having no influence on either C1+2 or STX synthesis . The evidence presented in this study suggests a possible difference between the metabolism of STX and the C1+2 toxins and indicated a high turnover rate of STX biosynthetic enzymes in C . raciborskii T3.

J Med Chem, 2004 Sep 9, 47(19), 4710 - 5
Design and synthesis of a nitrogen mustard derivative stabilized by apo-neocarzinostatin; Urbaniak MD et al.; Neocarzinostatin (NCS) is an antitumor antibiotic comprising a 1:1 protein-chromophore complex and exhibits cytotoxic action through DNA cleavage via H-abstraction . Cytotoxic activity resides with the chromophore 1 alone, while the protein (apoNCS) protects and transports labile 1 . The naphthoate portion (2) of NCS chromophore (1) is important for binding to apoNCS and DNA intercalation . In this paper we describe our attempts to use apoNCS to improve the hydrolytic stability of novel bifunctional DNA alkylating agents . The nitrogen mustards, melphalan and chlorambucil, were both conjugated to 2, and the biological activities of these conjugates were assessed . Chlorambucil did not benefit from conjugation . The melphalan conjugate (6) formed covalent DNA adducts at guanine bases and exhibited greater in vitro cytotoxic activity than unmodified melphalan . Fluorescence and NMR spectroscopy showed that 6 binds to apoNCS . Binding to apoNCS-protected 6 reduced the extent of hydrolysis of the conjugate . This novel approach demonstrates for the first time that an enediyne apo-protein can be used to improve the stability of substances that are of potential interest in cancer chemotherapy.

HNO . 2004 Sep 1; {Epub ahead of print}
{Gradenigo syndrome-still a threatening complication of otitis media}; Bloching M et al.; Intracranial complications of acute otitis media are rare in the time of a specific antibiotic therapy . We report about the case of a 13-year-old female patient with an incompletely cured otitis media which was followed by a petrous apicitis presenting abducens nerve palsy . She was successfully treated by a combination of surgical intervention, high dose intravenous antibiotics, systemic corticoid-therapy and hyperbaric oxygen therapy.

J Formos Med Assoc, 2004 Aug, 103(8), 613 - 7
Safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in Taiwanese infants; Shao PL et al.; BACKGROUND AND PURPOSE: The prevalence of antibiotic-resistant pneumococci has increased markedly in Taiwan since the 1990s . The prevention of pneumococcal infection by effective vaccination is an urgent need . The purpose of this study was to assess the safety and immunogenicity of heptavalent pneumococcal conjugate vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) in Taiwanese infants . METHODS: Sixty healthy Taiwanese infants received heptavalent pneumococcal conjugate vaccine at 2, 4 and 6 months of age in an open-label, non-comparative trial . Routine diphtheria-tetanus-pertussis vaccines were concomitantly administered . Side effects were recorded and the antibody titer to each of the 7 pneumococcal serotypes was measured before vaccination and 1 month after the third vaccination . RESULTS: Mild to moderate local reactions at the injection site were the common findings (17 to 30%) after vaccination but were not correlated with the number of vaccinations . Fever, restlessness, fussiness, and loss of appetite were the most common systemic reactions (22 to 53%) . After 3 doses of vaccine, the geometric mean concentration of immunoglobulin G showed a significant rise (p < 0.001) to all 7 pneumococcal serotypes . More than 95% of infants had antibody titer > or = 0.15 microg/mL of all serotypes, and 93% (serotype 23F) to 100% (serotypes 4 and 19F) of infants achieved an antibody titer > pr = 1 microg/mL . CONCLUSION: Inoculation with the heptavalent pneumococcal conjugate vaccine including the prevalent serotypes in Taiwan is safe and effective in preventing pneumococcal disease in Taiwanese children.

J Formos Med Assoc, 2004 Aug, 103(8), 607 - 12
Risk factors for wound infection after cholecystectomy; Chuang SC et al.; BACKGROUND AND PURPOSE: Surgical site infection (SSI) after cholecystectomy is a common problem . The aim of this study was to identify the possible risk factors for the development of SSI . METHODS: 545 consecutive patients who received open (125) or laparoscopic (420) cholecystectomy due to gallbladder disease during the years 1998 to 2000 were included in the study . Potential risk factors including clinical features, biochemical data, and operative types were analyzed by univariate and multivariate analysis . RESULTS: The overall incidence of SSI was 4.4% (24/545) . The wound complication rate was significantly lower in the laparoscopic group than in the open group (1.4% vs 14.4%, respectively) . Factors associated with SSI found by univariate analysis (p < 0.05) included age, gender, acute cholecystitis, white blood cell count, serum albumin, blood glucose and bilirubin level, type of surgery, operative time and positive bile culture . Stepwise logistic regression analysis showed that abnormal blood glucose {odds ratio (OR), 4.7; 95% confidence interval (CI), 1.6 to 13.5}, positive bile culture (OR, 3.5; 95% CI, 1.2 to 10.4), and open cholecystectomy (OR, 4.3; 95% CI, 1.3 to 13.6) were the most significant predictors of SSI . CONCLUSION: Poor control of diabetes mellitus before surgery, positive bile culture and open cholecystectomy significantly increased the rate of SSI . These findings indicate that better control of diabetes mellitus, and appropriate selection of surgical procedure and antibiotic regimen in the management of high-risk patients may reduce the incidence of postoperative SSI.

Ann Pharmacother, 2004 Oct, 38(10), 1588 - 92 Epub 2004 Aug 31.
Impact of fluconazole administration on outcomes in critically ill patients; Garrelts JC et al.; BACKGROUND: Serious infections caused by Candida spp . are an increasingly important cause of morbidity and mortality in critically ill patients . It is unclear which patients will benefit from therapy and at what point to institute treatment . OBJECTIVE: To evaluate the impact of administration of fluconazole therapy in critically ill trauma patients on mortality, length of hospital stay, incidence of deep-seated fungal infection, and positive fungal cultures from any site . METHODS: We conducted a retrospective, matched case-control study of 116 critically ill surgical trauma patients who did or did not receive fluconazole . Patients were followed until hospital discharge or death . A consecutive sample of 58 patients who received fluconazole was selected . A parallel group of patients was evaluated, from which 58 were matched with fluconazole-treated patients based on age (+/- 5 y), gender, and APACHE II score (+/- 3) . RESULTS: The groups of patients were well matched, with the exception of central venous catheter placement and broad-spectrum antibiotic use . We found no difference between groups in hospital mortality (21% vs 26%; p = 0.661) or incidence of deep-seated fungal infection (0% vs 2%; p = NS) . However, patients receiving fluconazole had a significantly longer stay in both the intensive care unit (ICU) (18 +/- 13 vs 7 +/- 11 days; p < 0.001) and hospital (25 +/- 15 vs 9 +/- 11 days; p < 0.001) . Fluconazole patients were significantly more likely to have Candida cultured from sites associated with colonization (43% vs 2%; p < 0.001), possibly explaining why they received fluconazole . CONCLUSIONS: We were unable to detect a benefit from use of fluconazole in our surgical trauma patient population . Isolation of Candida from the mouth or throat alone, in the absence of correlating clinical signs of infection, should not lead to initiation of fluconazole therapy . Fluconazole use should be reserved for carefully selected patients in the trauma ICU setting.

Respir Med, 2004 Sep, 98(9), 872 - 8
Prospective evaluation of pneumonia severity index in hospitalised patients with community-acquired pneumonia; van der Eerden MM et al.; The aim of the present study was to investigate whether the pneumonia severity index (PSI) could adequately predict the severity of community-acquired pneumonia (CAP) and could be used as a severity of illness classification system . Furthermore, reasons that may influence the decision to admit low risk patients were analysed . In a prospective study 260 patients with CAP were included . Stratification in five risk classes according to the PSI was compared with parameters that are closely related to severity of CAR A significant difference in severity parameters, such as length of stay (P < 0.001) and simplified acute physiologic score and acute physiologic and chronic health evaluation II score (P < 0.001) was found between the five risk classes . Furthermore, a positive British Thoracic Society (BTS) rule and modified BTS rule score was significantly more prevalent in the higher risk classes (P < 0.001) . The patient population had an average 30-day mortality of 10% and a mean Intensive Care Unit (ICU) admission rate of 8% . The mortality rate and ICU admission rate significantly differed between the five risk classes (P < 0.001), in which the highest ICU admission rate (40.9%) and the highest mortality percentage (40.9%) were both found in risk class V . Several clinical factors (n = 64), such as an exacerbation of chronic obstructive pulmonary disease in 17 patients and clinical appearance of being ill in 16 patients, lack of improvement on outpatient antibiotic therapy (n = 15) and social circumstances (n = 3) were reasons that influenced the decision to hospitalise low risk patients (n = 82) . The results show that the PSI adequately predicted the severity of CAP and can be used as a severity of illness classification in CAP . Clinical and social factors other than those mentioned in the PSI have to be considered when making the decision to hospitalise patients with CAP.

Am Fam Physician, 2004 Aug 15, 70(4), 689 - 96
Allergen immunotherapy; Huggins JL et al.; Allergen immunotherapy (also called allergy vaccine therapy) involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure . The major objectives of allergen immunotherapy are to reduce responses to allergic triggers that precipitate symptoms in the short term and to decrease inflammatory response and prevent development of persistent disease in the long term . Allergen immunotherapy is safe and has been shown to be effective in the treatment of stinging-insect hypersensitivity, allergic rhinitis or conjunctivitis, and allergic asthma . Allergen immunotherapy is not effective in the treatment of atopic dermatitis, urticaria, or headaches and is potentially dangerous if used for food or antibiotic allergies . Safe administration of allergen immunotherapy requires the immediate availability of a health care professional capable of recognizing and treating anaphylaxis . An observation period of 20 to 30 minutes after injection is mandatory . Patients should not be taking beta-adrenergic blocking agents when receiving immunotherapy because these drugs may mask early signs and symptoms of anaphylaxis and make the treatment of anaphylaxis more difficult . Unlike antiallergic medication, allergen immunotherapy has the potential of altering the allergic disease course after three to five years of therapy.

J Vasc Surg, 2004 Sep, 40(3), 413 - 8
Overt ischemic colitis after endovascular repair of aortoiliac aneurysms; Geraghty PJ et al.; OBJECTIVE: Controversy exists as to the cause of ischemic colitis complicating endovascular aneurysm repair . Occlusion of the hypogastric arteries (HAs) during endovascular repair of aortoiliac aneurysms (AIAs) results in a significant incidence of buttock claudication, and has been suggested as a causative factor in the development of postprocedural colonic ischemia, in addition to factors such as systemic hypotension, embolization of atheromatous debris, and interruption of inferior mesenteric artery inflow . To analyze the relationship between perioperative HA occlusion and postoperative ischemic colitis, we reviewed our experience over 2 years with Food and Drug Administration-approved endovascular graft devices for treatment of AIAs . METHODS: Elective repair of AIAs with bifurcated endovascular grafts was performed in 233 patients over a 2-year period . These included 184 AneuRx grafts, 17 Ancure grafts, and 32 Excluder grafts . During the experience, 44 patients (18.9%) underwent unilateral perioperative HA occlusion (28 right, 16 left) during the course of endovascular AIA repair, and 1 patient (0.4%) underwent bilateral HA occlusion . RESULTS: In 4 patients (1.7%) signs and symptoms of ischemic colitis developed 2.0 +/- 1.4 days postoperatively . In all patients the diagnosis was confirmed at sigmoidoscopy, and initial treatment included bowel rest, hydration, and intravenous antibiotic agents . Three patients with bilateral patent HAs required colonic resection 14.7 +/- 9.7 days after the initial diagnosis, and 2 of these 3 patients died in the postoperative period . Pathologic findings confirmed the presence of atheroemboli in the colonic vasculature in all 3 patients who underwent colonic resection . The fourth patient had undergone multiple manipulations of the left HA in an unsuccessful attempt to preserve patency of this vessel during AIA repair . This patient recovered completely with nonoperative management . Perioperative unilateral HA occlusion was not associated with a significantly higher incidence of postoperative ischemic colitis . CONCLUSION: Perioperative HA occlusion during aortoiliac open or endovascular surgery may contribute to development of the rare but potentially lethal complication of ischemic colitis . However, our extensive experience suggests that embolization of atheromatous debris to the HA tissue beds during endovascular manipulations, rather than proximal HA occlusion, is the primary cause of clinically significant ischemic colitis after endovascular aneurysm repair.

J Pharm Biomed Anal, 2004 Sep 3, 35(5), 1293 - 9
Binding study of drug with bovine serum album using a combined technique of microdialysis with flow-injection chemiluminescent detection; Huang Y et al.; Microdialysis coupled with flow-injection chemiluminescence (FI-CL) has been developed to determine the binding parameters of a drug binding to protein by using antibiotic tetracycline hydrochloride binding to bovine serum albumin as a model system . The drug and protein were mixed in different molar ratios in 0.067 M phosphate buffer, pH 7.4, and incubated at 37 degrees C in a water bath . The microdialysis probe was utilized to sample the mixed solution at a perfusion rate of 5 microL/min . The concentration of unbound tetracycline hydrochloride in the microdialysate was determined by FIA-CL . In vitro recovery of tetracycline hydrochloride under experimental conditions was 30.0% . The data obtained by the present microdialysis-FI-CL system was analyzed using the Scatchard analysis and Klotz plot . The results show that the Scatchard plot and Klotz plot are linear with good correlation coefficient, indicating a good agreement of the experimental data and to the theoretical equation . The FIA chemiluminescence system combined with microdialysis developed in this work demonstrated its use for determination of interaction between drug and protein by using relatively simple instrument.

Aliment Pharmacol Ther, 2004 Jul, 20 Suppl 2, 31 - 41
Helicobacter pylori infection: anything new should we know?
Basset C, Holton J, Gatta L, Ricci C, Bernabucci V, Liuzzi G, Vaira D.
Over the past year, 2003-4, there have been a number of studies consolidating previous work in relation to pathogenesis of disease, diagnosis and management of Helicobacter pylori . Studies into the pathogenesis of disease have identified the main adhesin of H . pylori as an important virulence marker and as a potential target for therapy . Molecular investigations of both the strain and host variations have identified the action of several of the virulence factors, e.g . cagA, vacA, on disrupting host cell signalling and the consequences in respect of the release of chemokines from the damaged gastric epithelium and the effect on apoptosis . Over the past year, there have been further diagnostic kits developed based on modifications of current technology . Two promising areas of research for diagnosis are the use of host/strain genome polymorphisms as a means of identifying high-risk patients who may develop severe disease and the use of proteomics to identify potential antigens of diagnostic (or therapeutic) use . The three main antibiotics that are used in first-line eradication regimens are clarithromycin, metronidazole and amoxycillin . Of these, metronidazole has the highest prevalence of resistance, followed by clarithromycin; amoxycillin resistance is only rarely reported . The decreasing success of current first-line therapy is the driving force for the development of new antibiotic combinations and a search for novel sources for chemotherapeutic agents and novel therapeutic targets.

Arch Pathol Lab Med, 2004 Sep, 128(9), 1000 - 3
Routine syndecan-1 immunohistochemistry AIDS in the diagnosis of chronic endometritis; Bayer-Garner IB et al.; CONTEXT: Chronic endometritis is reportedly observed in 3% to 10% of women undergoing endometrial biopsy for abnormal uterine bleeding . The diagnosis of chronic endometritis rests on the identification of the plasma cells . Their identification may be obscured by a mononuclear cell infiltrate, plasmacytoid stromal cells, abundant stromal mitoses, a pronounced predecidual reaction in late secretory endometrium, menstrual features, or secondary changes due to exogenous progesterone treatment prior to the biopsy . Syndecan-1 is a proteoglycan that is found on the cell surface of plasma cells and keratinocytes . Immunohistochemistry stains for this antibody may facilitate diagnosis of chronic endometritis . OBJECTIVE: To determine whether or not routine syndecan-1 immunohistochemistry will aid in the diagnosis of chronic endometritis . DESIGN: Immunohistochemistry stains for syndecan-1 were performed on 3 levels of 47 endometrial biopsies from patients with abnormal uterine bleeding . None of the patients had endometrial hyperplasia or an underlying malignancy . Clinical correlation and follow-up was attempted in 20 cases that showed evidence of plasma cells by syndecan-1 by immunohistochemistry . RESULTS: Plasma cells were identified in 20 cases, 7 of which were initially diagnosed as chronic endometritis . The remaining 13 positive cases were diagnosed as tubal metaplasia (1), secretory endometrium (4), proliferative endometrium (4), menstrual endometrium (1), endometrial polyp (1), secretory endometrium with endometrial polyp (1), and endometrial polyp with exogenous hormone effect (1) based on the original hematoxylin-eosin section . CONCLUSIONS: Syndecan-1 may be a useful adjunct in the diagnosis of chronic endometritis . Approximately half of the cases of chronic endometritis responded to an antibiotic regime; thus, this diagnosis is important and may potentially obviate the need for surgical intervention.

J Cardiol, 2004 Jul, 44(1), 33 - 8
{Vegetative cardiac metastases of oral cavity cancer: an autopsy case report}; Moriya J et al.; A 60-year-old man was admitted to our hospital for evaluation of intracardiac vegetative masses detected by echocardiography in September 2001 . He had undergone surgery for oral cavity cancer in 1999 . He presented with severe embolic symptoms including cerebral infarction, but had few symptoms of heart failure . Antibiotic therapy was started under the diagnosis of infective endocarditis, but the embolic symptoms persisted . An autopsy revealed that the intracardiac vegetative masses consisted of tumor cells originating from the oral cavity cancer . Intravascular tumor thrombi were also found widely distributed in other organs such as the liver, lung, spleen and kidney, and had similar histological features . This is a very rare case of cardiac metastases of oral cavity cancer without adhesion to the endocardium or other myocardial tissue.

Pediatr Pulmonol, 2004 Oct, 38(4), 314 - 20
Treatment with tobramycin solution for inhalation reduces hospitalizations in young CF subjects with mild lung disease; Murphy TD et al.; Our objective was to study the effect of tobramycin solution for inhalation (TSI; TOBI, Chiron Corp.) on lung function decline rate in 400 young persons with cystic fibrosis (CF) and mild lung disease . Effects on hospitalization, antibiotic use, school days missed, and nutritional status also were determined . This was an open-label, randomized (stratified by sex and age group, i.e., 6-10 and 11-15 years), parallel-group, multicenter study . Routine subject management (control group) was compared to routine management plus 28 days of twice-daily TSI inhalation, followed by 28 days off the drug (TSI group) for 56 weeks . Primary efficacy endpoints included rate of lung function decline (as measured by forced expiratory volume in 1 sec; FEV(1)), hospitalization, and concomitant antibiotic use . Safety was assessed by analysis of treatment-emergent adverse events . Only 184 of 400 planned subjects were recruited and randomized (93 to the TSI group, and 91 to the control group) . Enrollment was ended after 2 years because of difficult recruitment . An interim safety review showed a 2.42-fold risk of respiratory hospitalization for control group subjects (P = 0.020), and the study was terminated . Sixty-three subjects (34.2%) completed the entire study (30 in the TSI group, or 32.3%; and 33 in the control group, or 36.3%) . Significantly fewer TSI subjects were hospitalized for worsening of respiratory symptoms (11.0% vs . 25.6%; P = 0.011), and fewer TSI subjects were hospitalized overall (16.5% vs . 27.8%; P = 0.065) . Fewer TSI subjects received antibiotics other than the study drug (78.0% vs . 95.6%), and significantly fewer received oral antibiotics (76.9% vs . 91.1%; P = 0.009) . No other safety or adverse event differences were observed . In conclusion, significant reductions in respiratory hospitalizations, concomitant antibiotic use, and a trend towards improvement in percent predicted forced expiratory flow (FEF(25-75)) provide evidence of a clinical benefit of TSI use in young persons with CF and mild lung disease . An effect on lung function decline rate could not be evaluated as planned, due to inadequate enrollment and early study termination.

J Biol Chem, 2004 Nov 5, 279(45), 46995 - 7002 Epub 2004 Aug 27.
Role of Lys-32 residues in R67 dihydrofolate reductase probed by asymmetric mutations; Hicks SN et al.; R67 dihydrofolate reductase (R67 DHFR) is a novel protein encoded by an R-plasmid that confers resistance to the antibiotic, trimethoprim . This homotetrameric enzyme possesses 222 symmetry, which imposes numerous constraints on the single active site pore, including a "one-site-fits-both" strategy for binding its ligands, dihydrofolate (DHF) and NADPH . Previous studies uncovered salt effects on binding and catalysis (Hicks, S . N., Smiley, R . D., Hamilton, J . B., and Howell, E . E . (2003) Biochemistry 42, 10569-10578), however the one or more residues that participate in ionic contacts with the negatively charged tail of DHF as well as the phosphate groups in NADPH were not identified . Several studies predict that Lys-32 residues were involved, however mutations at this residue destabilize the R67 DHFR homotetramer . To study the role of Lys-32 in binding and catalysis, asymmetric K32M mutations have been utilized . To create asymmetry, individual mutations were added to a tandem array of four in-frame gene copies . These studies show one K32M mutation is tolerated quite well, whereas addition of two mutations has variable effects . Two double mutants, K32M:1+2 and K32M: 1+4, which place the mutations on opposite sides of the pore, reduce kcat . However a third double mutant, K32M: 1+3, that places two mutations on the same half pore, enhances kcat 4- to 5-fold compared with the parent enzyme, albeit at the expense of weaker binding of ligands . Because the kcat/Km values for this double mutant series are similar, these mutations appear to have uncovered some degree of non-productive binding . This non-productive binding mode likely arises from formation of an ionic interaction that must be broken to allow access to the transition state . The K32M:1+3 mutant data suggest this interaction is an ionic interaction between Lys-32 and the charged tail of dihydrofolate . This unusual catalytic scenario arises from the 222 symmetry imposed on the single active site pore.

FASEB J, 2004 Oct, 18(13), 1565 - 7 Epub 2004 Aug 27.
A dual-color fluorescence imaging-based system for the dissection of antiangiogenic and chemotherapeutic activity of molecules; Sengupta S et al.; We have developed a simple yet sensitive dual color fluorescence-based technique for dissecting the tumor-neovascularization relationship and evaluated the susceptibility of each component to therapeutic interventions . Green fluorescent protein (GFP)-expressing melanoma cells were cocultured with endothelial cells on different three-dimensional (3-D) matrices and exposed to multiple growth factors and molecules with established anti-angiogenic or anticancer activities . Cells were fixed and stained with propidium iodide, imaged using a confocal microscope, and stereologically analyzed . Three-dimensionality of the system was tested by depth-coding and pseudocolor 3-D reconstruction in the z-axis . Selective ablation of the tumor cells was affected by the anthracycline antibiotic doxorubicin . Treatment with vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) promoted the neovascular responses on matrigel and collagen-1 matrices . VEGF-induced angiogenesis was inhibited after treatment with combretastatin and thalidomide . In contrast, HGF exerted a protective effect against these anti-angiogenics in a matrigel matrix . However, this effect was lost when the matrix was substituted with collagen, suggesting that the extracellular matrix impinges on cellular function, possibly through an Akt-mediated mechanism . The VEGF-receptor antagonist PTK787 also selectively ablated the VEGF-induced angiogenic effect without inhibiting the HGF-induced response, demonstrating the sensitivity of the system to detect modulation of distinct signal cascades . The current model encompasses the possibility of studying tumor-angiogenesis-matrix interaction on the same platform, expanding the rapid screening of novel molecules in a simulated clinicopathological setting.

Org Lett, 2004 Sep 2, 6(18), 3131 - 4
Synthesis of analogue structures of the p-quinone methide moiety of kendomycin; Green MP et al.; {reaction: see text} The synthesis of two model p-quinone methide ring systems of the antibiotic and antiosteoporotic compound kendomycin is reported . Two approaches were examined in detail, and the two-step (i) demethylation and (ii) DMDO oxidation were found to be reliable and generally applicable . Additionally, it was found that oxidation of a benzofuran by NaIO(4) on silica produced a long-lived semiquinone radical.

Clin Lab, 2004, 50(7-8), 387 - 94
The detection of Brucella spp . using PCR-ELISA and real-time PCR assays; Al Dahouk S et al.; Brucellosis is a worldwide 're-emerging' zoonosis causing high economic losses and severe human disease . Consequently, rapid and reliable, sensitive and specific, easy to perform and automated detection systems for Brucella spp . are urgently needed to allow early diagnosis and adequate antibiotic therapy in time . Real-time PCR assays using hybridization probes meet all these requirements . In 2003 various assays have been developed and evaluated for use in human and animal brucellosis . Genus-specific real-time PCR assays e.g . based on the bcsp31 gene will lead to an early diagnosis but for the purpose of epidemiological surveillance a species-specific real-time PCR deriving from the conventional AMOS (AbortusMelitensisOvisSuis)-PCR is necessary . Advantages and disadvantages of the different methods for real-time detection of Brucella spp . and a newly developed PCR-ELISA system for the high throughput of clinical samples will be discussed.

Obstet Gynecol Surv, 2004 Sep, 59(9), 678 - 89
An evidence-based approach to the evaluation and treatment of premature rupture of membranes: Part II; Canavan TP et al.; Preterm premature rupture of membranes (PPROM) occurs in 3% of pregnancies and is responsible for one third of all preterm births . In part I of this series, the definition, pathophysiology, and diagnosis of PPROM was reviewed . In this part, treatment is discussed . Adjunctive antibiotic and corticosteroid therapy has the strongest evidence for improving neonatal outcome . Treatment is gestational age-dependent and will be influenced by local neonatal intensive-care unit (NICU) survival statistics . This review presents the available evidence and grades it according to the U.S . Preventative Task Force recommendations . LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize the data on the use of labor inhibition in the setting of PPROM, list potential antibiotics regimens that are recommended for prophylaxis in patients with PPROM, to describe the benefits of corticosteroid administration in patients with PPROM, and to outline potential management strategies for patients with PPROM based on gestational age.

J Antimicrob Chemother, 2004 Oct, 54(4), 798 - 802 Epub 2004 Aug 25.
Risk factors for anaemia in patients on prolonged linezolid therapy for chronic osteomyelitis: a case-control study; Senneville E et al.; OBJECTIVES: The intrinsic properties of the new antibiotic linezolid make it an attractive candidate for the treatment of chronic osteomyelitis . However, data regarding the tolerance of long-term linezolid administration are still lacking . METHODS: The medical charts of patients given linezolid for >4 weeks were retrospectively analysed, especially their haematology . In a case-control study, we compared the respective characteristics of patients who developed anaemia during linezolid therapy and those who did not . RESULTS: Forty-five adults with chronic osteomyelitis received 600 mg linezolid intravenously twice daily for 7 days, and then orally, for a mean total duration of 15.9 weeks (range, 6-36) . Anaemia episodes requiring blood transfusion occurred in 13/45 patients (28.9%) . Median time from treatment initiation to anaemia onset was 7.4 weeks (range, 4-16) . Anaemia was significantly associated with premature linezolid therapy cessation (P = 0.0012) . No linezolid-related thrombocytopenia was observed . By univariate analysis, four variables were associated with the occurrence of anaemia: age >58 years, alcohol abuse, diabetes mellitus and low haemoglobin before linezolid treatment . Logistic regression analysis revealed two independent risk factors for anaemia: age >58 years (OR = 20.5, 95% CI 0.69-599; P = 0.0001) and pre-treatment haemoglobin <10.5 g/dL (OR = 16.49, 95% CI 1.06-255; P = 0.04) . CONCLUSIONS: Profound anaemia may occur in adult patients with chronic osteomyelitis on prolonged linezolid therapy, and often necessitates linezolid cessation . These patients are likely to be aged >58 years and to have low pre-treatment haemoglobin . The results for the present series might help physicians to identify patients who should not be given long-term linezolid treatment for chronic osteomyelitis.

Clin Neuropathol, 2004 Jul-Aug, 23(4), 173 - 7
Cranial and intracranial actinomycosis; Sundaram C et al.; Five patients with central nervous system actinomycosis are presented . There were risk factors in 2 patients like penetrating head injury and tetralogy of Fallot . All the cases were diagnosed by histopathology . Four patients recovered after surgery and antibiotic therapy, and 1 patient died.

Klin Mikrobiol Infekc Lek, 2004 Aug, 10(4), 191 - 4
{Marseille fever imported from Spain}; Freibergerova M et al.; The authors are presenting a case of young female with Marseille fever contracted in Spain . The clinical manifestation of the illness was characterized by fevers, exanthema, headache and a typical skin rash ("the black spot") and prompted the authors to strongly consider the diagnosis of Marseille fever and to initiate appropriate antibiotic therapy . The diagnosis was confirmed later by serology . The article introduces new taxonomy of Rickettsial species and presents an overview and epidemiological aspects of specific diseases caused by them . The clinical manifestation, diagnosis and treatment of Marseille fever are discussed in greater detail.

J Dairy Sci, 2004 Aug, 87(8), 2702 - 8
Milk loss and treatment costs associated with two treatment protocols for clinical mastitis in dairy cows; Shim EH et al.; The objective of this study was to compare milk loss and treatment costs for cows with clinical mastitis that were given antibiotics in addition to supportive treatment or supportive treatment alone . Between January 1994 and January 1996, 116,876 daily milk records on 676 lactations were taken at the University of Illinois Dairy Research Farm . Clinical mastitis was diagnosed during 124 lactations with 25,047 daily milk records, and 1417 of the daily milk records were on days when clinical mastitis was present . Cows with clinical mastitis were randomly assigned to one of 2 treatment groups: N (supportive treatment only) or A (antibiotics in addition to supportive treatment) . Extent of antibiotic and supportive treatment varied according to twice daily severity scores . Projected and actual daily milk yields were estimated utilizing a random regression test-day model, and the differences were summed over 305 d of lactation to estimate lactational milk yield loss . The actual amount of discarded milk was added to milk yield loss to determine total milk loss per lactation . A cost analysis that included milk loss and treatment costs was then performed . Cows with clinical mastitis that were given only supportive treatment lost 230 +/- 172 kg (mean +/- standard error of mean {SEM}) more milk and incurred 94 +/- 51 dollars (SEM) more cost per lactation than cows given antibiotics and supportive treatment . Cows given only supportive treatment showed a response pattern of 305-d milk yield loss and economic loss per lactation that varied 2 to 3 times as much as cows treated with antibiotics . Based on reduced milk loss, better reliability (less variable response), and lower economic loss, the addition of antibiotics to supportive treatment was more efficacious and cost effective than supportive treatment alone.

Optometry, 2000 Aug, 71(8), 511 - 8
Topical ophthalmic drugs and the pediatric patient; Chung I et al.; BACKGROUND: More than 80% of the drugs on the market labeled for adult use contain no information on pediatric use-even for drugs commonly prescribed for pediatric patients . Without adequate pediatric labeling information, practitioners may be prescribing medications and placing their pediatric patients at risk for adverse reactions . METHODS: This article reviews the 98 most commonly used or prescribed topical ophthalmic drugs (TODs) and provides a summary of their safety for use in children . Additionally, the article includes the best sources of information the practitioner can use to find information on the pediatric safety of TODs . RESULTS: There is pediatric use labeling for 51% of the TODs included in this article (specifically, by drug category, pediatric use safety profiles are present for 100% of anti-virals, 88% of antibiotics, 67% of anti-allergy drugs, 67% of diagnostic agents, 55% of steroid-antibiotic combinations, 54% of lubricants, 50% of nonsteroidal anti-inflammatory drugs (NSAIDs), 31% of steroids, and 11% of glaucoma medications) . CONCLUSION: Sufficient pediatric safety labeling information is available to the practitioner for topical antibiotics, anti-allergy medications, antivirals, lubricants, and diagnostic pharmaceutical agents . Little or no information is available on the pediatric safety of topical steroids and glaucoma medications . For the majority of the steroid and glaucoma drugs, pediatric use is labeled "not recommended" (NR).

Ginecol Obstet Mex, 2001 May, 69, 185 - 8
{Neumopericardium and spontaneous post partum subcutaneus emphysema . A case report and literature review}; Velasco Alva SM et al.; The barotrauma cases related to childbirth are an uncommon event, especially the neumopericardium . This entity must be suspected in a patient with subcutaneuos emphysema and confirmed by chest X-ray . The management is based on closed observation, support measures and antibiotic to prevent infection . The radiological follow up is important to evaluate the resolution of this problem . The patient must be followed with caution if the neumopericardium increases because this could lead to a cardiac tamponade with fatal consequences . The description of a case diagnosed and managed in our hospital is done herein which evolution was satisfactory towards resolution of the pneumopericardium without the need of further intervention.

Invest Ophthalmol Vis Sci, 2004 Sep, 45(9), 2978 - 84
Mitomycin C-induced reduction of keratocytes and fibroblasts after photorefractive keratectomy; Kim TI et al.; PURPOSE: To investigate the effects of mitomycin C (MMC) on the number of keratocytes and the proliferation of fibroblasts after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UV-B) irradiation . METHODS: The right eyes of New Zealand White rabbits in Groups 1, 2, and 3 (n = 18 each) underwent PRK to correct -10 diopters with 5 mm optical zone . Sponges soaked with 0.02% MMC were applied to the right eyes of Group 1 rabbits for 2 minutes . Antibiotic ointment was applied daily to all rabbits until the epithelium healed completely, after which 0.02% MMC eye drops were applied twice daily to the right eyes in Group 2 until 4 weeks after PRK . Three weeks after PRK, the right eyes of all the remaining rabbits were exposed to 100 mJ/cm2 C UV-B radiation . Corneal haziness was assessed biomicroscopically using the Fantes scale every 3 weeks . Six eyes of each group were each enucleated 3, 6, and 12 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with TUNEL stain . The tissues were evaluated immunohistochemically with antibody to alpha-smooth muscle actin (SMA) . Cellular changes in the anterior stroma and epithelial basement membrane were evaluated by electron microscopy . RESULTS: Corneal haze was observed after PRK and was aggravated by UV-B irradiation . A single intraoperative application of MMC immediately after PRK induced opacity and apoptosis of keratocytes . Twelve weeks after PRK, MMC significantly reduced corneal haze, the number of keratocytes, apoptotic cells, and fibroblasts, even after UV-B irradiation . Relatively large numbers of apoptotic and SMA-positive cells were found only in PRK-treated, non-MMC treated rabbits (Group 3), even after 12 weeks . Three weeks after PRK, dying stromal cells showed cell shrinkage, and chromatin condensation was observed in all treated groups by electron microscopy . Twelve weeks after PRK, fewer keratocytes and inflammatory cells were observed just beneath the epithelial layer in Group 1 than in any of the other groups . CONCLUSIONS: MMC is a potent inhibitor of corneal haze induced by PRK . MMC reduced the number of keratocytes and fibroblasts after PRK and UV-B irradiation . Although MMC would improve the clinical results of PRK, it has significant toxicity on corneal keratocytes, which did not disappear until 3 months after PRK . Copyright Association for Research in Vision and Ophthalmology

Vet Parasitol, 2004 Sep 2, 123(3-4), 257 - 64
Viability of Sarcocystis neurona sporocysts after long-term storage; Elsheikha HM et al.; The effect of long-term storage on the viability and infectivity of Sarcocystis neurona sporocysts was investigated . S . neurona sporocysts were harvested from the small intestine of Virginia opossums from 1996 to 2002 and stored at 4 degrees C . Viability of sporocysts was assessed by propidium iodide (PI) exclusion assay, in vitro excystation and development in tissue cultures, and bioassay in gamma-interferon gene knockout (gamma-IFN-KO) mice . The rate of excystation was apparently unaffected by long-term storage; sporocysts retained their ability to excyst after 7 years of storage at 4 degrees C . However, the ability of sporocysts to exclude PI stain, to invade and proliferate in cells in vitro, and to cause disease and lesions in gamma-IFN-KO mice appeared to decline as sporocysts age . The results demonstrated that sporocysts of S . neurona were able to survive and maintain moderate to high viability for up to 7 years when stored in phosphate buffered saline and Hank's balanced salt solution containing antibiotic-antimycotic mixture at 4 degrees C.

Ann Univ Mariae Curie Sklodowska {Med}, 2003, 58(2), 163 - 7
Mycoses--prophylaxis and treatment; Warminska J et al.; An increase in the mycotic infections has been observed in recent decades . It is the effect of the development of industry, large migrations, living in huge aglomerations, usage of the public swimming-pools, wearing impervious clothes and shoes . Systemic diseases: diabetes, obesity, hormonal disorders, immune and food deficiency, AIDS, neoplasms and prescription drugs: antibiotics, corticosteroids and immunosuppressants, cause mycoses . Mycoses belong to chronic diseases, they are difficult to treat and very often recur . A lot of antimycotic drugs are known, but the most effective are azoles and alliloamines . An intensive research is conducted on introduction of new and more effective and cheaper preparations.

Braz Dent J, 2004, 15(1), 79 - 81 Epub 2004 Aug 16.
Oral myiasis treated with ivermectin: case report; Shinohara EH et al.; Oral myiasis is a rare pathology and a risk to the patient's life . Conventional treatment is mechanical removal of the larvae (maggots) one by one, which is painful, distressing, and embarrassing both to the patient and to the dentist . We present a case report of a patient with cerebral palsy that had oral myiasis treated successfully with ivermectin . The use of this antibiotic in humans, its mechanism of action and indications are discussed.

J Biol Chem, 2004 Oct 22, 279(43), 45139 - 47 Epub 2004 Aug 18.
Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1alpha . Functional implications in hepatic cholesterol and glucose metabolism; Bhalla S et al.; Previous studies show that feedback inhibition of bile acid production by bile acids is mediated by multiple mechanisms, including activation of pregnane X receptor (PXR) . Consistent with these studies, the antibiotic rifampicin, a ligand for human PXR, reduces hepatic bile acid levels in cholestasis patients . To delineate the mechanisms underlying PXR-mediated suppression of bile acid biosynthesis, we examined the functional cross-talk between human PXR and HNF-4, a key hepatic activator of genes involved in bile acid biosynthesis including the cholesterol 7-alpha hydroxylase (CYP7A1) and sterol 12-alpha hydroxylase (CYP8B1) genes . Treatment with rifampicin resulted in repression of endogenous human CYP7A1 expression in HepG2 cells that was reversed by PXR small interfering RNA . The coactivator PGC-1 enhanced transcriptional activity of HNF-4, and this enhancement was suppressed by rifampicin-activated PXR . Endogenous PGC-1 from mouse liver extracts bound to PXR, and recombinant PGC-1 directly interacted with both PXR and HNF-4 in vitro . Rifampicin-dependent interaction of PXR with PGC-1 was shown in cells by coimmunoprecipitation, and intranuclear localization studies using confocal microscopy provided further evidence for this interaction . In chromatin immunoprecipitation studies, rifampicin treatment did not inhibit HNF-4 binding to the native promoters of CYP7A1 and CYP8B1 but resulted in dissociation of PGC-1 and concomitant gene repression . Most interestingly, these rifampicin effects were also observed in the phosphoenolpyruvate carboxykinase gene that contains a functional HNF-4-binding site and is central to hepatic gluconeogenesis . Our study suggests that ligand-activated PXR interferes with HNF-4 signaling by targeting the common coactivator PGC-1, which underlies physiologically relevant inhibitory cross-talk between drug metabolism and cholesterol/glucose metabolism.

Cleve Clin J Med, 2004 Jul, 71(7), 569 - 76
Spontaneous bacterial peritonitis: recent data on incidence and treatment; Parsi MA et al.; Recent studies have shown that spontaneous bacterial peritonitis (SBP) is more common than previously thought among patients admitted to the hospital with cirrhotic ascites . Other recent studies have clarified which antibiotic regimens are most successful for treatment and prevention, often shortening the duration of treatment . Still, the prognosis is poor and recurrence of SBP is common.

J Laryngol Otol, 2004 Jul, 118(7), 561 - 5
How serious are oral infections?
Baqain ZH, Newman L, Hyde N.
Life-threatening conditions following dental infections have been rare since antibiotics were introduced into the world of medicine . However, infections spreading through the soft tissues of the head and neck are encountered occasionally and mortality is still reported as a result of sepsis or airway embarrassment . A case of Ludwig's angina from odontogenic infection that progressed into mediastinitis and pericarditis is presented . The steps adopted in the management of this case highlight the significance of early recognition and diagnosis of the source of deep cervical infections, the importance of securing the airway, effecting surgical drainage and aggressive intravenous antibiotic therapy.

Eur J Biochem, 2004 Sep, 271(17), 3556 - 66
Sequence selective binding of bis-daunorubicin WP631 to DNA; Fox KR et al.; We have used footprinting techniques on a wide range of natural and synthetic footprinting substrates to examine the sequence-selective interaction of the bis-daunorubicin antibiotic WP631 with DNA . The ligand produces clear DNase I footprints that are very different from those seen with other anthracycline antibiotics such as daunorubicin and nogalamycin . Footprints are found in a diverse range of sequences, many of which are rich in GT (AC) or GA (TC) residues . As expected, the ligand binds well to the sequences CGTACG and CGATCG, but clear footprints are also found at hexanucleotide sequences such GCATGC and GCTAGC . The various footprints do not contain any particular unique di-, tri- or tetranucleotide sequences, but are frequently contain the sequence (G/C)(A/T)(A/T)(G/C) . All sequences with this composition are protected by the ligand, though it can also bind to some sites that differ from this consensus by one base pair.

Eur J Clin Microbiol Infect Dis, 2004 Sep, 23(9), 696 - 8 Epub 2004 Aug 13.
Low prevalence of genital candidiasis in children; Banerjee K et al.; In order to determine the prevalence of culture-proven candida infection in children with genital symptoms, a retrospective case-note review was performed to identify all symptomatic children with a culture result positive for Candida spp . during a 15-month period . Between May 2000 and July 2001, a total of 570 specimens were received from 473 children, and 34 positive culture results were recorded for specimens taken from 32 patients . Of these patients, 19 were in the 0-3-year age group, six in the 3-9-year age group and seven in the 9-12-year age group . Underlying risk factors for infection included prematurity, immunosuppression and prior antibiotic therapy . Three children were suspected to have experienced sexual abuse . Candida infection is uncommon in toilet-trained prepubertal girls, and empirical antifungal therapy is not indicated in this age group unless there are well-recognised predisposing factors . If a Candida sp . is isolated from a genital tract specimen taken from a 3-9-year-old girl, then a specific cause needs to be sought .

Ophthalmologe, 2004 Sep, 101(9), 945 - 54; quiz 955-6
{Connatal dacryostenoses . Clinical picture and treatment}; Busse H; Connatal dacryostenosis involves obstructions of the lacrimal passages in all parts of the system as well as supernumerary structures like the connatal fistula of the lacrimal sac . Usually intervention in infants with aplasia of the puncta is not necessary . When the lacrimal passages are involved in coloboma of the lids or facial cleft, reconstruction depends on the usable tissue of the lacrimal system . Treatment of connatal mucocele consists of digital expression of the pseudo-tumor . In cases of connatal dacryostenosis due to Hasner's membrane in infants, massage of the lacrimal sac as well as application of antibiotic eye drops and detumescent nose drops is indicated . After 5 or 6 months high-pressure irrigation with the hollow probe of Bangerter is necessary . Important is the postoperative treatment with detumescent and antibiotic eye drops as well as with detumescent nose drops for 1-2 weeks . In acute inflammation, treatment of the inflammation is the first goal of therapy, which may be combined with incision of the abscess . This can be performed by transcutaneous incision as well as by endonasal intervention in cooperation with a rhinologist.

JAMA, 2004 Aug 18, 292(7), 828 - 36
Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial; Meydani SN et al.; CONTEXT: Respiratory tract infections are prevalent in elderly individuals, resulting in increased morbidity, mortality, and use of health care services . Vitamin E supplementation has been shown to improve immune response in elderly persons . However, the clinical importance of these findings has not been determined . OBJECTIVE: To determine the effect of 1 year of vitamin E supplementation on respiratory tract infections in elderly nursing home residents . DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial was conducted from April 1998 to August 2001 at 33 long-term care facilities in the Boston, Mass, area . A total of 617 persons aged at least 65 years and who met the study's eligibility criteria were enrolled; 451 (73%) completed the study . INTERVENTION: Vitamin E (200 IU) or placebo capsule administered daily; all participants received a capsule containing half the recommended daily allowance of essential vitamins and minerals . MAIN OUTCOME MEASURES: Incidence of respiratory tract infections, number of persons and number of days with respiratory tract infections (upper and lower), and number of new antibiotic prescriptions for respiratory tract infections among all participants randomized and those who completed the study . RESULTS: Vitamin E had no significant effect on incidence or number of days with infection for all, upper, or lower respiratory tract infections . However, fewer participants receiving vitamin E acquired 1 or more respiratory tract infections (60% vs 68%; risk ratio {RR}, 0.88; 95% confidence interval {CI}, 0.76-1.00; P =.048 for all participants; and 65% vs 74%; RR, 0.88; 95% CI, 0.75-0.99; P =.04 for completing participants), or upper respiratory tract infections (44% vs 52%; RR, 0.84; 95% CI, 0.69-1.00; P =.05 for all participants; and 50% vs 62%; RR, 0.81; 95% CI, 0.66-0.96; P =.01 for completing participants) . When common colds were analyzed in a post hoc subgroup analysis, the vitamin E group had a lower incidence of common cold (0.67 vs 0.81 per person-year; RR, 0.83; 95% CI, 0.68-1.01; P =.06 for all participants; and 0.66 vs 0.83 per person-year; RR, 0.80; 95% CI, 0.64-0.98; P =.04 for completing participants) and fewer participants in the vitamin E group acquired 1 or more colds (40% vs 48%; RR, 0.83; 95% CI, 0.67-1.00; P =.05 for all participants; and 46% vs 57%; RR, 0.80; 95% CI, 0.64-0.96; P =.02 for completing participants) . Vitamin E had no significant effect on antibiotic use . CONCLUSIONS: Supplementation with 200 IU per day of vitamin E did not have a statistically significant effect on lower respiratory tract infections in elderly nursing home residents . However, we observed a protective effect of vitamin E supplementation on upper respiratory tract infections, particularly the common cold, that merits further investigation.

Biophys J, 2004 Nov, 87(5), 3264 - 76 Epub 2004 Aug 17.
Cholesterol and ergosterol influence nystatin surface aggregation: relation to pore formation; Coutinho A et al.; Nystatin interaction with liposomes mimicking fungal and mammalian membranes (ergosterol- and cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) large unilamellar vesicles, respectively) was studied by fluorescence spectroscopy . The activity of this antibiotic was also measured using a pyranine fluorescence detected K+/H+ exchange assay . Nystatin mean fluorescence lifetime varied with the antibiotic concentration and ergosterol content (0-30 mol%) of the lipid vesicles . It sharply increased from 5 to 37 ns upon reaching 100 molecules per liposome, reporting nystatin oligomerization in the membrane . Concomitantly, spectral alterations typical of excitonic coupling were detected and there was a pronounced increase in the initial rate of pore formation by nystatin . These findings suggest that nystatin exerts its antibiotic activity via a two-stage mechanism: at low antibiotic concentrations, surface-adsorbed monomeric antibiotic molecules perturb the lipid packing, changing the permeability properties of the ergosterol-rich liposomes . Upon reaching a critical threshold, nystatin mode of action switches to the classical model of transmembrane aqueous channel formation . In the presence of cholesterol-containing POPC liposomes, neither nystatin spectroscopic properties, nor the kinetics of K+ efflux varied with the antibiotic concentration suggesting that in this case the first stage of antibiotic mode of action always prevails or the assemblies formed by nystatin and cholesterol are very loose.

Proc R Soc Lond B Biol Sci, 2004 Sep 7, 271(1550), 1791 - 8
Exploiting a mutualism: parasite specialization on cultivars within the fungus-growing ant symbiosis; Gerardo NM et al.; Fungus-growing ants, their cultivated fungi and the cultivar-attacking parasite Escovopsis coevolve as a complex community . Higher-level phylogenetic congruence of the symbionts suggests specialized long-term associations of host-parasite clades but reveals little about parasite specificity at finer scales of species-species and genotype-genotype interactions . By coupling sequence and amplified fragment length polymorphism genotyping analyses with experimental evidence, we examine (i) the host specificity of Escovopsis strains infecting colonies of three closely related ant species in the genus Cyphomyrmex, and (ii) potential mechanisms constraining the Escovopsis host range . Incongruence of cultivar and ant relationships across the three focal Cyphomyrmex spp . allows us to test whether Escovopsis strains track their cultivar or the ant hosts . Phylogenetic analyses demonstrate that the Escovopsis phylogeny matches the cultivar phylogeny but not the ant phylogeny, indicating that the parasites are cultivar specific . Cross-infection experiments establish that ant gardens can be infected by parasite strains with which they are not typically associated in the field, but that infection is more likely when gardens are inoculated with their typical parasite strains . Thus, Escovopsis specialization is shaped by the parasite's ability to overcome only a narrow range of garden-specific defences, but specialization is probably additionally constrained by ecological factors, including the other symbionts (i.e . ants and their antibiotic-producing bacteria) within the coevolved fungus-growing ant symbiosis.

J Agric Food Chem, 2004 Aug 25, 52(17), 5309 - 15
Analysis of matrix-bound nitrofuran residues in worldwide-originated honeys by isotope dilution high-performance liquid chromatography-tandem mass spectrometry; Khong SP et al.; A sensitive and selective isotope dilution liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESIMS/MS) method is presented for the simultaneous analysis of the metabolites of four nitrofuran veterinary drugs, that is, furazolidone, furaltadone, nitrofurantoin, and nitrofurazone, in honey samples . The method entails a combined hydrolysis of protein-bound drug metabolites and derivatization of the resulting metabolites with 2-nitrobenzaldehyde (NBA) during an overnight incubation, followed by a liquid-liquid extraction and a cleanup on a polymeric solid-phase extraction cartridge . Mass spectral acquisition is carried out in the positive ion mode by applying multiple reaction monitoring (MRM) of three diagnostic transition reactions for each analyte under survey . A reliable quantification is obtained by the use of one deuterated analogue per analyte (NBA-d(4) derivative) . The method has been validated in honey according to the European Union criteria for the analysis of veterinary drug residues in food . Expressed in underivatized nitrofuran metabolite concentrations, the decision limits (CCalpha) ranged within 0.07-0.46 microg/kg, and the detection capabilities (CCbeta) were within 0.12-0.56 microg/kg . The method has been successfully applied in a survey of honeys of various geographical origins, showing that furazolidone is the main nitrofuran antibiotic administered to treat bacterial diseases of bees.

Acta Biomed Ateneo Parmense, 2004 Apr, 75(1), 22 - 5
Effectiveness of intranasal corticosteroids; Grzincich G et al.; Intranasal corticosteroids (IC) are most commonly prescribed to treat allergic rhinitis (perennial and seasonal) . There are now many IC available to treat rhinitis, all effective on nasal obstruction, rhinorrhea, sneezing, itching and post-nasal drip . IC are superior to oral antihistamines for the relief of all nasal symptoms; however, antihistamines are first line therapy if allergic conjunctivitis coexists . At present the data do not support the use of IC in the management of otitis media with effusion (OME), nasal polyposis and sinusitis, but when topical IC are administered together with antibiotic therapy they facilitate a more rapid improvement of symptoms.

Clin Lab Sci, 2004 Summer, 17(3), 172 - 7
Paroxysmal nocturnal hemoglobinuria; Smith LJ; Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder resulting from a somatic mutation in the hematopoietic stem cell . It is characterized by intravascular hemolysis, cytopenias, frequent infections, bone marrow hypoplasia, and a high incidence of life-threatening venous thrombosis . An absent glycosylphosphatidylinositol (GPI)-anchored receptor prevents several proteins from binding to the erythrocyte membrane . These include the complement-regulatory proteins, CD55 and CD59, whose absence results in enhanced complement-mediated lysis . Patients present with anemia and hemoglobinuria . Laboratory diagnosis includes the sucrose hemolysis test, Ham acid hemolysis test, and fluorescent-activated cell analysis . There is considerable overlap between PNH, aplastic anemia, and myelodysplastic syndrome and some cases evolve into acute leukemia . Treatment is mainly supportive consisting of transfusion therapy, anticoagulation, and antibiotic therapy . Hematopoietic stem cell transplantation may be curative.

Dtsch Med Wochenschr, 2004 Aug 20, 129(34-35), 1802 - 5
{Pancreatico-pleural fistula in chronic pancreatitis with necrosis of the pancreatic tail}; Neumann S et al.; HISTORY AND CLINICAL FINDINGS: A 68-year-old male was admitted to the hospital with progressive dyspnea and thoracic pain radiating to the shoulder, back and upper abdomen . The patients medical history included hypertension, diabetes and chronic pancreatitis with splenic vein thrombosis . INVESTIGATIONS: Laboratory findings showed no signs of myocardial infarction, but pronounced inflammation . The ECG was normal . Chest X-ray revealed a massive left-side pleural effusion with partial lung atelectasis . An abdominal CT-scan showed no signs of acute pancreatitis . Puncture of the pleural effusion revealed elevated amylase and lipase . ERCP showed pancreatic duct stenosis, partial necrosis of the pancreatic body and peripancreatic necrosis with a pancreatico-pleural fistula . TREATMENT AND CLINICAL COURSE: After ballon-dilatation of the constricted pancreatic duct, a plastic stent and a nasopancreatic drain were inserted into the necrosis and into the fistula . Drainage and antibiotic therapy led to regression of the necrosis within 3 weeks . With external pleural drainage and octreotide therapy almost complete regression of the pleural effusion and closure of the pancreatico-pleural fistula could be achieved within 3 weeks . CONCLUSION: Complications of chronic pancreatitis such as necrosis and fistulas are rare, but important differential diagnoses in patients with chronic pancreatitis and chest pain . A combination of transpapillary or transgastral endoscopic drainage procedures and pleural drainage, sometimes with additional octreotide therapy is the treatment of choice.

Arch Otolaryngol Head Neck Surg, 2004 Aug, 130(8), 975 - 8
Clinical outcomes after revision endoscopic sinus surgery; Bhattacharyya N; OBJECTIVE: To determine if patients undergoing revision endoscopic sinus surgery (ESS) for chronic rhinosinusitis obtain significant symptomatic benefit from surgery . DESIGN: Prospective controlled clinical trial . METHODS: Adult patients undergoing revision ESS were evaluated preoperatively with a computed tomographic scan and the Rhinosinusitis Symptom Inventory . After the revision ESS, patients were reevaluated with the Rhinosinusitis Symptom Inventory . Data were analyzed for symptom score changes and effect sizes, changes in medication, and economic variables . Improvements in sinonasal symptom scores, medication use, and economic variables were compared with those of a contemporaneous control group of patients undergoing primary ESS and matched for age, sex, and Lund score . RESULTS: The 21 patients (mean age, 44.8 years) who completed evaluation after revision ESS had a mean follow-up of 12.4 months . Mean preoperative Lund score was 12.6 . Large effect sizes indicating significant symptom improvements were noted for nasal obstruction (effect size, -1.9), hyposmia (-0.9), and headache (-0.6), as well as nasal (-1.1) and total symptom domains (-0.9; P<.05 in all cases) . Nasal steroid and nonsedating antihistamine use did not decrease significantly after ESS, but oral antibiotic use showed a downward trend (net change, - 2.9 wk/y; P =.23) . Improvements in clinical symptoms were statistically similar to corresponding improvements in the matched cohort of patients undergoing primary ESS . CONCLUSIONS: The symptomatic relief that revision ESS can provide for patients with refractory chronic rhinosinusitis is similar to that following a primary ESS . However, many patients undergoing revision ESS require continued intense medical management of their chronic rhinosinusitis.

Ann Intern Med, 2004 Aug 17, 141(4), 305 - 13
Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia; Dodek P et al.; BACKGROUND: Ventilator-associated pneumonia (VAP) is an important patient safety issue in critically ill patients . PURPOSE: To develop an evidence-based guideline for the prevention of VAP . DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews . STUDY SELECTION: The authors systematically searched for relevant randomized, controlled trials and systematic reviews that involved mechanically ventilated adults and were published before 1 April 2003 . DATA EXTRACTION: Physical, positional, and pharmacologic interventions that may influence the development of VAP were considered . Independently and in duplicate, the authors scored the validity of trials; the effect size and confidence intervals; the homogeneity of results; and safety, feasibility, and economic issues . DATA SYNTHESIS: Recommended: The orotracheal route of intubation, changes of ventilator circuits only for each new patient and if the circuits are soiled, use of closed endotracheal suction systems that are changed for each new patient and as clinically indicated, heat and moisture exchangers in the absence of contraindications, weekly changes of heat and moisture exchangers, and semi-recumbent positioning in the absence of contraindications . Consider subglottic secretion drainage and kinetic beds . Not recommended: Sucralfate to prevent VAP in patients at high risk for gastrointestinal bleeding and topical antibiotics to prevent VAP . Because of insufficient or conflicting evidence, no recommendations were made about systematically searching for maxillary sinusitis, chest physiotherapy, the timing of tracheostomy, prone positioning, prophylactic intravenous antibiotics, or intravenous plus topical antibiotics . LIMITATIONS: No formal economic analysis was performed, and patient perspectives were not considered . CONCLUSION: If effectively implemented, this guideline may decrease the morbidity, mortality, and costs of VAP in mechanically ventilated patients.

Res Microbiol, 2004 Sep, 155(7), 525 - 34
Cloning, characterization and heterologous expression of the aspartokinase and aspartate semialdehyde dehydrogenase genes of cephamycin C-producer Streptomyces clavuligerus; Tunca S et al.; Carbon flow through the lysine branch of the aspartate biosynthetic pathway is a rate-limiting step in the formation of cephamycin C, a broad spectrum beta-lactam antibiotic produced by Streptomyces clavuligerus . In this study, genes which encode the enzymes catalyzing the first two steps of the aspartate pathway, ask (aspartokinase) and asd (aspartate semialdehyde dehydrogenase), in S . clavuligerus NRRL 3585 were cloned and sequenced . Nucleotide sequencing and codon preference analysis revealed three complete open reading frames (ORFs) . ORF2 starts within ORF1 and terminates by utilizing the same stop codon as ORF1, an arrangement typical of many ask genes . ORF3 is located 2 nucleotides downstream of ORF1,2 . Database comparisons with these proteins identified ORF1 as the large (alpha) subunit of aspartokinase, ORF2 as the small (beta) subunit of aspartokinase and ORF3 as the aspartate semialdehyde dehydrogenase . The cloned genes were functionally expressed in auxotrophic Escherichia coli strains, CGSC5074 (ask(-)) and E . coli CGSC5080 (asd(-)), the two enzymes were partially purified from E . coli cell extracts and their kinetic parameters were determined . The effects of end product amino acids and diaminopimelic acid on the activity of Ask and Asd enzymes were also described.

Arch Biochem Biophys, 2004 Sep 15, 429(2), 215 - 23
Investigation of the electrophysiological properties of enniatins; Kamyar M et al.; Enniatins are cyclohexadepsipeptides produced by various species of the genus Fusarium, and are known to have ionophoric, antibiotic, and in vitro hypolipidaemic properties . With the patch clamp technique in the inside-out mode it could be shown that enniatin easily incorporates into the cell membrane in which it forms cation-selective pores . This feature is characterized by unitary transitions to conductance levels typical for channels, ion selectivity, rectification, conductivity in the pS range, and block . A model of vertically stacked enniatin molecules that form sandwich complexes is suggested . Like gramicidin enniatin is a passive channel . Single channel properties for the isomers enniatin A1, B, and B1 differed from each other . This implies an influence of the substituted moieties on the complexation of cations . Electrical activity was followed by changes in intracellular ion concentrations, which are consistent with depolarization of the membrane resting potential, shortening of action potential duration, and reduced contractility.

Biochem Biophys Res Commun, 2004 Sep 10, 322(1), 223 - 31
Tunicamycin preserves intercellular junctions, cytoarchitecture, and cell-substratum interactions in ATP-depleted epithelial cells; George SK et al.; Pretreatment with the nucleoside antibiotic tunicamycin was found to protect cultured renal epithelial cells in the face of ATP-depletion, in large part by preserving junctional and cellular architecture . Tunicamycin pretreatment of Madin-Darby canine kidney cells not only preserved E-cadherin staining at the plasma membrane, but also inhibited ATP-depletion-mediated E-cadherin degradation . Electron microscopic analysis, together with the preservation of the staining patterns of the tight junction marker ZO-1, the apical/microvillar marker gp135, and basolateral marker Na/K-ATPase suggested that tunicamycin preserved the junctional complex and the polarized epithelial cell phenotype . Tunicamycin pretreatment also prevented reductions in the filamentous actin content of the cells, as well as preserving Golgi architecture . Moreover, a quantitative measure of cell adhesion demonstrated that tunicamycin pretreatment resulted in a fivefold increase in attachment of cells to the substratum (77% versus 16%) . Thus, pretreatment with tunicamycin protects polarized epithelial cells from ischemic injury through the preservation of epithelial cell architecture, intercellular junctions, and cell-substratum interactions in the setting of intracellular ATP-depletion.

J Control Release, 2004 Aug 27, 98(3), 355 - 65
In vitro delivery of doxycycline hydrochloride based on a porous membrane-based aqueous-organic partitioning system; Fan Q et al.; This work investigated the controlled release of an antibiotic drug, doxycycline HCl, from its solution/suspension in an organic solvent in a reservoir through a porous membrane employing aqueous-organic partitioning with or without a mouse skin to simulate a skin patch . The reservoir contained the agent in solution in the solvent 1-octanol or its dispersion/solution in the solvent mineral oil with or without an enhancer . The porous membranes employed with water-in-pores were hydrophobic Celgard 2400 of polypropylene and hydrophilized polyvinylidene fluoride (PVDF) . Conventional Franz diffusion cells as well as a skin patch were used . The transport rates of the agent observed through both Celgard and PVDF membranes could be successfully described by Fickian diffusion through the water-filled pores when the appropriate organic-aqueous partition coefficient was incorporated . The light mineral oil-based system yielded much higher permeability due to the much lower organic-aqueous partition coefficient of the antibiotic in light mineral oil . The optimized skin patch systems yielded drug flux and permeability values similar to their relevant membrane systems . The addition of a mouse skin beneath the patch drastically reduced the drug transfer rate . Among a number of enhancers used to correct this deficiency, linoleic acid at 10% level in the reservoir solution was found to yield a flux of 2.7 +/- 0.5 microg/cm(2) h and a permeability of 2.7e - 04 +/- 5.0e - 05 cm/h . These values are higher than the values available in literature obtained with full thickness human cadaver skin.

Zhonghua Jie He He Hu Xi Za Zhi, 2004 Jul, 27(7), 455 - 9
{A multicenter randomized controlled study of the efficacy and safety of oseltamivir in the treatment of influenza in a high risk population}; Lin JT et al.; OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of influenza in a high risk population . METHODS: A randomized, open, control trial was conducted from Nov . 2002 to Feb . 2003 . Patients with chronic respiratory disease, such as chronic bronchitis, obstructive emphysema, bronchial asthma, bronchiectasis or chronic cardiac disease, and with symptoms of influenza were enrolled . They should satisfy the following criteria: Fever > or = 37.8 degrees C plus at least two of the following influenza symptoms: coryza/nasal congestion, sore throat, cough, myalgia/muscle aches and pain, fatigue, headache and chills/sweats . Within 48 h after the onset of the symptoms, the patients were randomly assigned to oseltamivir group (oseltamivir 75 mg, twice daily for 5 days) or control group (symptom relief medicine only) . RESULTS: Fifty-six of the 108 recruited patients were identified as influenza-infected through laboratory test . They were defined as intent-to-treat infected population (ITTI) (27 oseltamivir, 29 control) . The duration of influenza symptom was 64 h shorter (36.7%) and AUC score of the influenza symptom was decreased by 618 (43.1%) in the oseltamivir group as compared with those in the control group . The fever duration was 46.8 h (45.0%) less in the oseltamivir group than that in the control group . It took 6 d for the oseltamivir group and 11 days for the control group to recover to the basic health status . Secondary complications such as bronchitis, sinusitis and pneumonia occurred 11% (3/27) in the oseltamivir group and 45% (13/29) in the control group . The treatment expense for influenza and its complication was 587.4 RMB in the oseltamivir group and 786.5 RMB in the control group, which showed no significant difference (P = 0.246) . CONCLUSIONS: It is suggested that oseltamivir is effective and well tolerated in patients with chronic respiratory or cardiac diseases . It can reduce the fever duration and severity of influenza symptom, and decrease the incidence of secondary complications and antibiotic use, while does not increase the total medical cost.

Otolaryngol Pol, 2004, 58(3), 427 - 8
Chlamydia pneumoniae IgA seropositivity and sudden sensorineural hearing loss; Dunne AA et al.; A prospective study was designed to evaluate a possible role of an endured infection with Chlamydia pneumoniae or Chlamydia trachomatis as a cause for sudden sensorineural hearing loss . For this in 60 patients with a first episode of a sensorineural hearing loss and-60 sex-matched and aged-matched controls, following a complete otoneurological diagnosis blood tests for IgA, IgM and IgG with regard to Chlamydia pneumoniae and trachomatis were evaluated . We found a statistically significant higher prevalence of IgA positivity of Chlamydia pneumoniae in patients with sudden sensorineural hearing loss (chi2-test, p < 0.017) . For this, Chlamydia pneumoniae may be a possible cause for sudden sensorineural hearing loss . A targeted antibiotic therapy, as it has been discussed for myocardial infarction, might possibly open an additional treatment option for sudden sensorineural hearing loss.

J Clin Oncol, 2004 Aug 15, 22(16), 3350 - 6
Prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor decrease febrile neutropenia after chemotherapy in children with cancer: a meta-analysis of randomized controlled trials; Sung L et al.; PURPOSE: To determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) used in children with cancer reduce the rate of febrile neutropenia, hospitalization duration, documented infection rate, parenteral antibiotic duration, amphotericin B use, or infection-related mortality . METHODS: We included studies in this meta-analysis if their populations consisted of children, if there was randomization between CSFs and placebo or no therapy, if CSFs were administered prophylactically (before neutropenia or febrile neutropenia), and if chemotherapy treatments preceding CSFs and placebo or no therapy were identical . From 971 reviewed study articles, 16 were included . RESULTS: The mean rate of febrile neutropenia in the control arms was 57% (range, 39% to 100%) . Using a random effects model, CSFs were associated with a reduction in febrile neutropenia, with a rate ratio of 0.80 (95% CI, 0.67 to 0.95; P =.01), and a decrease in hospitalization length, with a weighted mean difference of -1.9 days (95% CI, -2.7 to -1.1 days; P <.00001) . CSF use was also associated with reduction in documented infections (rate ratio, 0.78; 95% CI, 0.62 to 0.97; P =.02) and reduction in amphotericin B use (rate ratio, 0.50; 95% CI, 0.28 to 0.87; P =.02) . There was no difference in duration of parenteral antibiotic therapy (weighted mean difference, -4.3; 95% CI, -10.6 to 2.0 days; P =.2) or infection-related mortality (rate ratio, 1.02; 95% CI, 0.34 to 3.06; P =.97) . CONCLUSION: CSFs were associated with a 20% reduction in febrile neutropenia and shorter duration of hospitalization; however, CSFs did not reduce infection-related mortality.

Plant Cell Rep, 2004 Nov, 23(6), 426 - 34 Epub 2004 Nov.
Sugarcane white leaf phytoplasma in tissue culture: long-term maintenance, transmission, and oxytetracycline remission; Wongkaew P et al.; Sugarcane white leaf (SCWL)-diseased sugarcane plants collected from Udornthani Province, in north-eastern Thailand, were the source for tissue culture experiments . Explants from axillary buds, meristem tips, and leaves grew optimally in Murashige-Skoog medium containing 0.5 mg/l alpha-naphthaleneacetic acid, 0.5 mg/l 6-benzylaminopurine, and 15% coconut water . Callus development and shoot/root proliferation were more rapid in cultures from diseased than from healthy plants . Disease symptoms continued for 6 years after culture initiation, and SCWL phytoplasma persisted, as confirmed by polymerase chain reaction using both 16S rDNA and 16S-23S rDNA primers . Phytoplasmas in the cultured plantlets were transmissible by grafting to sugarcane and periwinkle, and by feeding of the leafhopper vector Matsumuratettix hiroglyphicus to sugarcane . Although 50% of the plantlets were killed by oxytetracycline at 500 mg/ml, 70-100% of plantlets grown with 200-500 mg/ml oxytetracycline showed symptom remission through 5-8 subcultures . Typical phytoplasma-like bodies, visible by electron microscopy in sieve tubes of untreated diseased plantlets, were absent in antibiotic-treated plantlets . Thus, tissue culture provides a convenient and reliable in vivo system for investigation of SCWL phytoplasma.

HNO, 2004 Aug, 52(8), 737 - 9
{An endocranial complication of sinogenic origin without initial classical neurological symptoms}; Schumacher S et al.; A 14 year old male developed a subdural empyema with a leptomeningeal infection of sinogenic origin . Initially, there were none of the expected neurological symptoms such as worsening headaches, vomiting, alteration in the level of consciousness and neck stiffness . Later, focal neurological deficits and seizures occurred . An endonasal sinus drainage was performed simultaneously with a neurosurgical exploration . We started an antibiotic therapy . All neurological deficits disappeared rapidly.

Br J Plast Surg, 2004 Sep, 57(6), 556 - 60
Factors influencing the development of wound infection following free-flap reconstruction for intra-oral cancer; Cloke DJ et al.; Wound infection following tissue transfer in head and neck oncology is common . Factors known to be associated with infective complications include blood transfusion, pre-operative radiotherapy, duration of surgery, duration of pre-operative stay and a history of smoking . The present study specifically examined 100 consecutive patients on a standard antibiotic protocol undergoing free flap reconstruction following resection of cancers of the oral cavity or oropharynx . Despite prophylactic antibiotics, 21 patients developed a head and neck wound infection . No statistically significant association was found between infective wound complications and a history of smoking, pre-operative radiotherapy or chemotherapy, length of pre-operative hospital stay, duration of surgery, or number of units of blood transfused . We conclude that, in this group of patients, wound infection is a common and difficult problem, but with no statistically significant association with any of the variables studied.

Wiad Lek, 2004, 57(3-4), 119 - 22
{Management of patients with popliteal aneurysms}; Niedziela P; The aneurysms of the popliteal artery constitute 75% of all aneurysms of peripheral arteries . All operatively treated patients were divided into two groups . The first group comprised 53 patients with symptomatic aneurysms . The second group consisted of 19 patients with asymptomatic, electively treated aneurysms detected in most cases accidentally, during medical examination . The operative treatment consisted of the ligation or removal of the aneurysm and the reconstruction of the blood flow via shunting graft . After the operation low molecular weight heparin in the dose of 4000 units IC anti-Xa was administered and given to the patients once daily in the period of 4 to 7 days . No oral anticoagulants were applied . Antibiotics (mostly cephalosporins of the second generation) were administered preventively in the perioperative period . The results of the treatment were assessed in the period of one month from the operation, according to three-grade scale . Best results were obtained in the patients constituting the second group . The largest number of amputations on the level of upper and lower leg was carried out in the first group of patients . Obtained data allowed to state that recognition of the aneurysm of popliteal artery was in all cases an indication to an operative treatment . Better results were observed when the operation was conducted electively and when the patient's own vein was used to reconstruct the blood flow.

Trans R Soc Trop Med Hyg, 2003 Sep-Oct, 97(5), 573 - 6
Escherichia coli enterovirulent phenotypes in Zambians with AIDS-related diarrhoea; Kelly P et al.; Persistent diarrhoea is a major cause of morbidity and mortality in AIDS patients, and consequently an important public health problem in sub-Saharan Africa . Although intestinal protozoa and bacteria are detected in many of these patients, a substantial proportion of disease remains unexplained even after intensive investigation . HEp-2 cell adherent Escherichia coli have been described in AIDS patients with persistent diarrhoea, but their contribution to the overall burden of disease is not yet defined . We studied HEp-2 cell adherence of E . coli isolates from 116 adult Zambian AIDS patients and 153 healthy controls obtained in 1993 or 1998-99 . Enteroaggregative, enteropathogenic, and diffusely adherent phenotypes were observed in E . coli isolates from both AIDS patients and controls, but cytotoxic phenotypes were only isolated from the AIDS patients . There was no evidence of seasonality in the frequency of isolation, and there was no evidence of long-term carriage . Light and electron microscopy of distal duodenal biopsies did not reveal any bacteria closely associated with the brush border . Isolates were less susceptible to amoxycillin, tetracycline, and sulfonamides than to newer antibiotics . Enterovirulent E . coli appear to contribute to intestinal disease in AIDS patients in Zambia but asymptomatic carriage is common . Antibiotic trials should be carried out.

Am J Hematol, 2004 Sep, 77(1), 22 - 5
Bronchus-associated lymphoid tissue lymphoma arising in a patient with bronchiectasis and chronic Mycobacterium avium infection; Gaur S et al.; We describe a 67-year-old woman with bronchiectasis and Mycobacterium avium complex infection who underwent wedge resection of her pulmonary infiltrates because they were progressing despite antibiotic therapy . In addition to the expected granulomatous changes, she was found to have a B-cell lymphoma of bronchus associated lymphoid tissue (BALT) . Despite normal bone marrow morphology, marrow involvement was demonstrated by flow cytometry . Her lymphoma remains suppressed with antimycobacterial therapy 6 months after resection of bulk disease .

Gut, 2004 Sep, 53(9), 1235 - 43
Challenge model for Helicobacter pylori infection in human volunteers; Graham DY et al.; BACKGROUND: A reliable challenge model is needed to evaluate Helicobacter pylori vaccine candidates . METHODS: A cag pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of H pylori obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers . Volunteers received 40 mg of famotidine at bedtime and 10(4)-10(10) cfu of H pylori in beef broth the next morning . Infection was confirmed by (13)C urea breath test ((13)C-UBT), culture, and histology . Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology . RESULTS: Twenty subjects (nine women and 11 men; aged 23-33 years) received a H pylori challenge . Eighteen (90%) became infected . Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved . Vomitus from one subject contained >10(3) viable/ml H pylori . By two weeks post challenge gastric histology showed typical chronic H pylori gastritis with intense acute and chronic inflammation . The density of H pylori (as assessed by cfu/biopsy) was similarly independent of the challenge dose . A minimal infectious dose was not found . Gastric mucosal interleukin 8 levels increased more than 20-fold by two weeks after the challenge . CONCLUSION: Challenge reliably resulted in H pylori infection . Infection was associated with typical H pylori gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the cag pathogenicity island . Experimental H pylori infection is one of the viable approaches to evaluate vaccine candidates.

Phytother Res, 2004 Jul, 18(7), 516 - 21
Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes . Part III . Apigenin, baicalelin, kaempherol, luteolin and quercetin; Psotova J et al.; Flavonoids are found universally in plants and act as free radical scavenging and chelating agents with antiinflammatory, antiischemic, vasodilating and chemoprotective properties . In this study, the antilipoperoxidative and cytoprotective effects of apigenin, baicalein, kaempferol, luteolin and quercetin against doxorubicin-induced oxidative stress were investigated in isolated rat heart cardiac myocytes, mitochondria and microsomes . After preincubation of cardiomyocytes with the test compounds for 1 h the cardiomyocytes were treated with the toxic agent, doxorubicin (100 micro M for 8 h) . Cardiomyocyte protection was assessed by extracellular LDH and cellular ADP and ATP production . Cytoprotection was concentration dependent for baicalein > luteolin congruent with apigenin > quercetin > kaempferol . All test compounds had signi fi cantly better protective effects than dexrazoxan, an agent currently used for adjuvant therapy during anthracycline antibiotic therapy . In microsomes/mitochondria the IC(50) values of lipid peroxidation inhibition for quercetin, baicalein, kaempferol, luteolin, and apigenin were 3.1 +/- 0.2/8.2 +/- 0.6, 3.3 +/- 0.3/9.6 +/- 0.5, 3.9 +/- 0.3/10.1 +/- 0.8, 22.9 +/- 1.7/18.2 +/- 0.7, and 338.8 +/- 23.1/73.1 +/- 6.4 mM, respectively . The antilipoperoxidative activity of apigenin differed from its cytoprotective effects, but correlated with the free radical scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and half peak oxidation potential (E(p/2)) . Apigenin was the least effective of the flavonoids studied in all models except the cardiomyocyte model where its cardiomyocyte cytoprotective effect was comparable to other compounds.

Neurology, 2004 Aug 10, 63(3), 547 - 9
Minocycline safety and tolerability in Huntington disease; Huntington Study Group; Minocycline is an antibiotic with anti-inflammatory and antiapoptotic properties that prolongs survival in a transgenic Huntington disease (HD) mouse model . In a double-blind, randomized, placebo-controlled study of minocycline in 60 HD patients, the authors determined that over 8 weeks, minocycline at 100 and 200 mg/day was well tolerated and safe in HD patients . Tolerability and adverse event frequency were similar between treatment and placebo groups.

BMC Health Serv Res . 2004 Aug 10;4(1):20.
Racial variations in processes of care for patients with community-acquired pneumonia; Mortensen EM et al.; BACKGROUND: Patients hospitalized with community acquired pneumonia (CAP) have a substantial risk of death, but there is evidence that adherence to certain processes of care, including antibiotic administration within 8 hours, can decrease this risk . Although national mortality data shows blacks have a substantially increased odds of death due to pneumonia as compared to whites previous studies of short-term mortality have found decreased mortality for blacks . Therefore we examined pneumonia-related processes of care and short-term mortality in a population of patients hospitalized with CAP . METHODS: We reviewed the records of all identified Medicare beneficiaries hospitalized for pneumonia between 10/1/1998 and 9/30/1999 at one of 101 Pennsylvania hospitals, and randomly selected 60 patients at each hospital for inclusion . We reviewed the medical records to gather process measures of quality, pneumonia severity and demographics . We used Medicare administrative data to identify 30-day mortality . Because only a small proportion of the study population was black, we included all 240 black patients and randomly selected 720 white patients matched on age and gender . We performed a resampling of the white patients 10 times . RESULTS: Males were 43% of the cohort, and the median age was 76 years . After controlling for potential confounders, blacks were less likely to receive antibiotics within 8 hours (odds ratio with 95% confidence interval 0.6, 0.4-0.97), but were as likely as whites to have blood cultures obtained prior to receiving antibiotics (0.7, 0.3-1.5), to have oxygenation assessed within 24 hours of presentation (1.6, 0.9-3.0), and to receive guideline concordant antibiotics (OR 0.9, 0.6-1.7) . Black patients had a trend towards decreased 30-day mortality (0.4, 0.2 to 1.0) . CONCLUSION: Although blacks were less likely to receive optimal care, our findings are consistent with other studies that suggest better risk-adjusted survival among blacks than among whites . Further study is needed to determine why this is the case.

Urology, 2004 Aug, 64(2), 218 - 22
Fournier's gangrene: experience with 25 patients and use of Fournier's gangrene severity index score; Yeniyol CO et al.; OBJECTIVES: To identify effective factors in the survival of patients with Fournier's gangrene and to determine the accuracy of the Fournier's gangrene severity index score . METHODS: In our clinic, 25 patients with Fournier's gangrene were treated between 1995 and 2000 . Data were collected about medical history, symptoms, physical examination findings, admission and final laboratory tests, timing and extent of surgical debridement, and antibiotic therapy used . RESULTS: The results were evaluated in two groups: those who died (n = 6) and those who survived (n = 19) . No statistically significant difference was found between the age of the survivors and those who died . The admission and final laboratory parameters that correlated statistically significantly with outcome included urea, creatinine, bicarbonate, sodium, potassium, total protein, albumin, leukocyte count, hematocrit, lactate dehydrogenase, and alkaline phosphatase . The greater mean extent of body surface area involved among patients who died was significantly different statistically from that of those who survived (5.4% and 2.1%, P < or =0.0001) . The mean Fournier's gangrene severity index score (FGSIS) for survivors was 3.0 +/- 1.8 compared with 12 +/- 2.4 for nonsurvivors . Regression analysis demonstrated a strong correlation between the Fournier's gangrene severity index score and the death rate (P < or =0.0001) . CONCLUSIONS: Patients' metabolic status and the extent of disease at presentation is an important factor in the prognosis of Fournier's gangrene . We suggest the clinical use of FGSIS, which is simple and objective when evaluating therapeutic options and predicting outcome.

Biochemistry, 2004 Aug 17, 43(32), 10295 - 301
Mechanistic studies of a flavin-dependent thymidylate synthase; Agrawal N et al.; The ThyA gene that encodes for thymidylate synthase (TS) is absent in the genomes of a large number of bacteria, including several human pathogens . Many of these bacteria also lack the genes for dihydrofolate reductase (DHFR) and thymidine kinase and are totally dependent on an alternative enzyme for thymidylate synthesis . Thy1 encodes flavin-dependent TS (FDTS, previously denoted as TSCP) and shares no sequence homology with classical TS genes . Mechanistic studies of a FDTS from Thermotoga maritima (TM0449) are presented here . Several isotopic labeling experiments reveal details of the catalyzed reaction, and a chemical mechanism that is consistent with the experimental data is proposed . The reaction proceeds via a ping-pong mechanism where nicotinamide binding and release precedes the oxidative half-reaction . The enzyme is primarily pro-R specific with regard to the nicotinamide (NADPH), the oxidation of which is the rate-limiting step of the whole catalytic cascade . An enzyme-bound flavin is reduced with an isotope effect of 25 (consistent with H-tunneling) and exchanges protons with the solvent prior to the reduction of an intermediate methylene . A quantitative assay was developed, and the kinetic parameters were measured . A significant NADPH substrate inhibition and large K(M) rationalized the slow activity reported for this enzyme in the past . These and other findings are compared with classical TS (ThyA) catalysis in terms of kinetic and molecular mechanisms . The differences between the FDTS proposed mechanism and that of the classical TS are striking and invoke the notion that mechanism-based drugs will selectively inhibit FDTS and will not have much effect on human (and other eukaryotes) TS . Since TS activity is essential to DNA replication, the unique mechanism of FDTS makes it an attractive target for antibiotic drug development.

Cent Afr J Med, 2003 Nov-Dec, 49(11-12), 130 - 4
Epidemiology and mortality of burns at the Queen Elizabeth Central Hospital Blantyre, Malawi; Komolafe OO et al.; OBJECTIVES: To determine the most common causes, population most at risk and the pattern of mortality of burn injuries at the Queen Elizabeth Central Hospital, Blantyre, Malawi . DESIGN: Retrospective cross sectional study . SETTING: Burns Unit, Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi . SUBJECTS: One thousand eight hundred and twenty five case files of burn patients admitted to the QECH, Blantyre, between January 1994 and December 1999, involving 941 male and 884 female patients among whom 145 were epileptic . MAIN OUTCOME MEASURE: Aetiology of burns and the population most at risk at the QECH, Blantyre . RESULTS: More males (52%) than females (48%) suffered from burns during the six year study period . Children below age five (55%) were most at risk while 89% were below 30 years of age . Hot water (38%) was the most common cause of burns, but among epileptic patients, it was open fire (83%) . While 71% of all inpatients had superficial burns (less than 10% TBSA) 22% had deep burns requiring grafting . Almost all the patients (98%) had multiple antibiotic therapy combined with topical application of silver sulfadiazine . Overall mortality was 12% but among the epileptic patients it was 16% . CONCLUSION: Children under five years of age were the major victims of burn injuries in this study . There is, therefore, need to mount effective awareness campaigns in order to target the root causes of burns in children.

Clin Exp Rheumatol, 2004 Jul-Aug, 22(4), 477 - 80
Lumbar pain in a married couple who likes cheese: brucella strikes again!
Taliani G, Bartoloni A, Tozzi A, Bartalesi F, Corti G, Paradisi F.
A 69-year-old man living in Florence reported fever and acute lumbar pain one month after transurethral resection of a superficial transitional cell carcinoma of the bladder . The radionuclide bone scan suggested metastatic lesions of the L3-L4 vertebrae . However cobalt treatment was ineffective . A bone biopsy of L4 showed an inflammatory pattern and antibiotic therapy was started which did not produce any clinical improvement . Six months after the onset of the back pain brucellar spondylitis was serologically diagnosed and treatment with doxycycline and streptomycin produced a significant clinical and radiological improvement . After 2 months the patient's wife presented with fever and lumbar pain, and brucellar spondylitis was diagnosed as well . An extensive epidemiological examination revealed that 8 months earlier the family had eaten unpasteurized goat cheese and serological examination of the entire family showed that 3 out of 4 members had significant titres of brucellar antibodies . Finally it was discovered that 4 months after consuming the cheese the third infected subject experienced an episode of epidydimoorchitis for which no diagnosis and effective treatment was found . This family cluster of brucellar infection indicates that a high degree of suspicion in the diagnosis of brucellosis is necessary even in non-endemic areas, to reduce the delay in the diagnosis and treatment of the disease and to prevent the occurrence of complications that may prove difficult to treat.

Yan Ke Xue Bao, 2004 Jul, 20(2), 77 - 9
{Observation on therapeutic effect of squamous blepharitis treated with liquefacient nitrogen cryotherapy}; Lin Z; PURPOSE: To observe the therapeutic effect of squamous blepharitis treated with liquefacient nitrogen cryotherapy . METHODS: 126 patients (234 eyes) with squamous blepharitis were randomly divided into two groups . Observation group 65 patients (120 eyes) were treated with liquefacient nitrogen cryotherapy adding antibiotic eye drops and ointments . Control group 61 patients (114 eyes) were treated with antibiotic eye drops and 2% yellow mercury oxide ointments . Both groups were treated for two courses, 20-25 days per course . RESULTS: Sixty-four eyes of observation group were cured, 30 eyes were improved and 26 eyes were ineffective . Thirty-two eyes of improved and ineffective patients were cured after an additional course . Total cured rate was 80% . Fourty-eight eyes of control group were cured, 30 eyes were improved and 36 eyes were ineffective . Total cured rate was 42.11% . The difference of two groups were significant (chi2=35.47, P < 0.01) . CONCLUSIONS: Liquefacient nitrogen cryotherapy was an effective method for squamous blepharitis.

Bone Marrow Transplant, 2004 Oct, 34(8), 693 - 702
Combined administration of alpha-erythropoietin and filgrastim can improve the outcome and cost balance of autologous stem cell transplantation in patients with lymphoproliferative disorders; Olivieri A et al.; We compared the use of G-CSF plus EPO in a group of 32 multiple myeloma and lymphoma patients with historical controls receiving G-CSF alone . Haemopoietic reconstitution was significantly faster in patients receiving G-CSF+EPO (group B), with a median time of 10 days to achieve an ANC count >0.5 x 10(9)/l, compared to 11 days in the historical group (A) . The median duration of severe neutropenia (ANC count <100/ml) was significantly shorter in group B compared to group A; platelet counts >20 x 10(9) and >50 x 10(9)/l were achieved at days + 13 and + 17, respectively in group B, compared to days + 14 and + 24, respectively, in group A (P = 0.015, 0.002) patients . The transfusion requirement was reduced in group B, with 0 (0-6) RBC units and 1 (0-5) platelet unit transfused in group B vs 2 RBC (0-9) and 2 platelet units (0-8) in group A . Median days of fever, antibiotic therapy and hospital stay were reduced in group B (9.5 days vs 22) . The mean cost of autotransplantation per group A patient was 23,988 Euro, compared with 18,394 Euro for a group B patient . Our study suggests that the EPO + G-CSF combination not only accelerates engraftment kinetics, but can also improve the clinical course of ASCT.

J Occup Environ Med, 2004 Aug, 46(8), 791 - 800
Management guidelines for laboratory exposures to agents of bioterrorism; Rusnak JM et al.; Over the past several years, funding for biodefense research has increased dramatically, leading to the possibility of increased laboratory-acquired infections with potential bioterrorism agents . The Special Immunizations Program at United States Army Medical Research Institute of Infectious Diseases reviewed its policy and management of potential occupational exposures (1989-2002) to assess guidelines for determining the risk of exposure and disease and to determine criteria for initiating postexposure prophylaxis (PEP) . Initiating antibiotic PEP was based primarily on exposure risk but was also influenced by vaccination status and agent virulence . PEP was given to nearly all moderate- and high-risk bacterial exposures, regardless of vaccination status, to most unvaccinated and subsets of vaccinated minimal-risk exposures, but generally not to negligible-risk exposures . Algorithms for evaluating and managing potential exposures are presented to provide guidance to other agencies as they begin to work with these agents.

Optom Vis Sci, 2004 Aug, 81(8), 586 - 90
Ophthalmomyiasis caused by the sheep bot fly Oestrus ovis in northern Iraq; Gregory AR et al.; Myiasis is the feeding of fly larvae on vertebrates . The sheep bot fly larva of Oestrus ovis is a mammalian parasite of the skin, nose, ears, and eyes . When the larvae infest and feed on the structures of the eye, the condition is termed ophthalmomyiasis . Most often this infestation is limited to the external structures of the eye and is referred to as ophthalmomyiasis externa . The features of this condition are severe local inflammation, positive foreign body sensation, erythema, and lacrimation . Vision may or may not be reduced, depending on involvement of the cornea . A 20-year-old white male soldier sought treatment for an inflamed eye and an irritated cornea OS . His eyelids were swollen with marked periorbital edema and conjunctival erythema OS . On slitlamp examination, small whitish organisms were viewed on the conjunctiva OS . The organisms were removed, preserved, and sent to Nova Southeastern University where they were identified as O . ovis first-stage larvae . The patient was treated with antibiotic ointment, and the inflammation resolved within 1 week . O . ovis has a worldwide distribution, and although sheep are the preferred host, humans may also serve as an intermediate host in the organism's life cycle . This case represents one of several reports of ophthalmomyiasis in the Middle East caused by O . ovis . U.S . troops stationed in Iraq and surrounding areas are vulnerable to eye infestation by fly larvae, and health care providers need to include this condition in their differential diagnosis of anterior segment inflammatory disorders.

Acta Crystallogr D Biol Crystallogr, 1997 Mar, 53(Pt 2), 151 - 9
Channels in the Gramicidin S-with-Urea Structure and their Possible Relation to Transmembrane Ion Transport; Tishchenko GN; The structure of membrane-active antibiotic cyclodecapeptide gramicidin S in the crystals of its complex with urea, C(60)H(92)N(12)0(10).0.(5){(NH(2))(2)CO}.7.94H(2)0, has been investigated with three-dimensional X-ray data by the automatic sequential approximation method . The crystals are trigonal, space group P3(1)21, a = 25.80(3), c= 21.49 (2) A, M(r) = 7968, calculated density = 1.088 mg m(-3), Z = 1 . Conventional R factor: R1 = 0.0943, wR2 = 0.2478 {I> 2sigma(I)} . The molecule possesses an antiparallel twisted beta-structure, with turns involving the Phe-Pro peptides . The Orn side chains extend on one side of the sheet, while the non-polar Val and Leu side chains are located on the other face . One of the Orn residues (namely Orn2) is linked by an intermolecular hydrogen bond to the O atom of Phe4 residue, the other is free . The side chains of the Phe residues have trans orientation (chi(1) approximately 180 degrees ) and those of the Val, Orn, Leu residues, except those of Orn2, have the preferential gauche orientation with the chi(1) angle close to 60 . Two side chains show statistical disorder and conformation of the Pro residues is C(s)-C(beta)-exo . There is half a urea molecule and also 7.94 water molecules distributed on 13 positions for each antibiotic molecule . A partially occupied and poorly ordered alcohol molecule had been identified . The gramicidin S molecules are arranged around the 3(1) axis in the form of a left-handed double spiral forming suggestive channels . The outer hydrophobic surface of the spiral is made of uncharged side radicals while the inside surface consists of the main-chain atoms, mainly O and N, and of ornithine side chains with N atoms at the ends . By changing the Orn side-chain conformation, the inner diameter of the channels may change from 3.4 to 6.3 A . Thus, ions and particles of rather large size may pass through the channel . The possibility of the creation of the gramicidin S channels in mitochondrial membranes has been noted by some biochemists . The channel complexes are close-packed in a hexagonal arrangement in the crystal . The CI(-) ions, present in abundance in the mother solution, are not found ordered in the crystals, which may indicate the absence of the charges in the terminal N atoms of the Orn residues.

Acta Crystallogr D Biol Crystallogr, 1993 May, 49(Pt 3), 311 - 7
The structure of an idarubicin-d(TGATCA) complex at high resolution; Gallois B; The crystal structure of the DNA hexamer d(TGATCA) complexed with the anthracycline antibiotic idarubicin has been determined at 1.6 A resolution . The asymmetric unit consists of a single hexamer oligonucleotide strand, one drug molecule and 35 water molecules . The complex crystallizes in the tetragonal space group P4(1)2(1)2, Z = 8 with lattice dimensions of a = b = 28.19 (3), c = 52.77 (4) A, V = 41 935 A(3) . The structure is isomorphous with a series of hexamer-anthracycline complexes and was solved by molecular replacement . Restrained least-squares methods interspersed with computer-graphics map inspection and model manipulation were used to refine the structure . The R factor is 0.22 for 2032 reflections with F >/= 3sigma(F) in the resolution range 8.0-1.6 A . The self-complementary DNA forms a distorted B-DNA double helix with two idarubicin molecules intercalated in the d(TpG) steps of the duplex . The duplex is formed by utilization of a crystallographic twofold axis of symmetry . The idarubicin chromophore is oriented at right angles to the long axis of the DNA base pairs with the anthracycline amino-sugar moiety positioned in the minor groove . Our structure determination allows for comparison with a d(CGATCG)-idarubicin complex recently reported . Despite the sequence alteration at the intercalation step, the structures are very similar . The geometry of the intercalation and the nature of the interactions are conserved irrespective of the DNA sequence involved in the binding.

Aliment Pharmacol Ther, 2004 Jul, 20 Suppl 1, 185 - 92
Effect of dietary anti-Helicobacter pylori-urease immunoglobulin Y on Helicobacter pylori infection; Suzuki H et al.; Recently, chicken egg yolk was recognized as an inexpensive antibody source, and the therapeutic usefulness of egg yolk immunoglobulin Y (IgY) in oral passive immunization has been investigated . Although multiple antibiotic treatments eradicate most Helicobacter pylori (H . pylori) infections, therapy fails in 10-15% of cases due to the development of drug resistance . Consequently, it is important that new, more broadly based therapies for the treatment of H . pylori infection should be identified . The present study evaluated the effect, on H . pylori infection, of IgY prepared from egg yolk of hens immunized with H . pylori urease (anti-HpU IgY) . Seventeen asymptomatic volunteers diagnosed as H . pylori-positive by the 13C-urea breath test (UBT) were orally administered anti-HpU IgY for 4 weeks . Four weeks later, UBT values were significantly decreased although no case showed H . pylori eradication . An H . pylori-positive 53-year-old female gastritis patient administered anti-HpU IgY plus lansoprazole for 8 weeks showed a decrease in serum pepsinogen (PG) I and UBT values as well as an increase in the PG I/II ratio . In conclusion, anti-HpU IgY may mitigate H . pylori-associated gastritis and partially attenuate gastric urease activity . Furthermore, anti-HpU IgY combined with antacids appears to ameliorate gastric inflammation . These encouraging results may represent a novel approach to the management of H . pylori-associated gastroduodenal disease.

Bull World Health Organ, 2004 May, 82(5), 354 - 63
Cotrimoxazole prophylaxis reduces mortality in human immunodeficiency virus-positive tuberculosis patients in Karonga District, Malawi; Mwaungulu FB et al.; OBJECTIVE: To estimate the impact of cotrimoxazole prophylaxis on the survival of human immunodeficiency virus (HIV)-positive tuberculosis (TB) patients . METHODS: A cohort study with a historical comparison group was conducted . End-of-treatment outcomes and 18-month survival were compared between TB patients registered in 1999 and patients registered in 2000 in Karonga District, Malawi . Case ascertainment, treatment and outpatient follow-up were identical in the two years except that in 2000 cotrimoxazole prophylaxis was offered to HIV-positive patients in addition to routine care . The prophylaxis was provided from the time a patient was identified as HIV-positive until 12 months after registration . Analyses were carried out on an intention-to-treat basis for all TB patients, and also separately by HIV status, TB type and certainty of diagnosis . FINDINGS: 355 and 362 TB patients were registered in 1999 and 2000, respectively; 70% were HIV-positive . The overall case fatality rate fell from 37% to 29%, i.e . for every 12.5 TB patients treated, one death was averted . Case fatality rates were unchanged between the two years in HIV-negative patients, but fell in HIV-positive patients from 43% to 24% . The improved survival became apparent after the first 2 months and was maintained beyond the end of treatment . The improvement was most marked in patients with smear-positive TB and others with confirmed TB diagnoses . CONCLUSION: Survival of HIV-positive TB patients improved dramatically with the addition of cotrimoxazole prophylaxis to the treatment regimen . The improvement can be attributed to cotrimoxazole because other factors were unchanged and the survival of HIV-negative patients was not improved . Cotrimoxazole prophylaxis should therefore be added to the routine care of HIV-positive TB patients.

Blood Purif, 2004, 22(4), 360 - 6 Epub 2004 Aug 03.
Dialysate leukocytes, sICAM-1, hyaluronan and IL-6: predictors of outcome of peritonitis?
Martikainen TA, Ekstrand AV, Honkanen EO, Teppo AM, Gronhagen-Riska C.
BACKGROUND/AIMS: Despite effective antibiotic therapy, peritonitis still remains a major problem in peritoneal dialysis (PD) . The aim of the present study was to investigate changes of CRP, dialysate leukocytes and IL-6, hyaluronan (HA) and sICAM-1 in dialysate during and after peritonitis and their association to the outcome of peritonitis . METHODS: Dialysate IL-6, HA and sICAM-1 were measured at the onset and on day 4, at the end of the treatment and 2 months after onset of peritonitis . Furthermore, CRP and dialysate leukocytes were measured on days 1-4 . RESULTS: All measured soluble factors were higher on the first and fourth day than at the end of the treatment . sICAM-1 and HA were lower at the end of the treatment in patients who later had a relapse/re-infection . IL-6 remained higher 2 months after clinically cured peritonitis . CRP and dialysate leukocytes were higher on day 4 in patients with poor outcome . CONCLUSIONS: Peritonitis causes increased excretion of soluble factors . Low concentrations of sICAM-1 and HA at the end of the treatment were negative prognostic indicators . Higher IL-6 levels after peritonitis could be a sign of ongoing inflammation in the peritoneal membrane . Delayed decrease in CRP and dialysate leukocytes may indicate poor outcome.

J Clin Microbiol, 2004 Aug, 42(8), 3589 - 93
Use of fatty acid RPMI 1640 media for testing susceptibilities of eight Malassezia species to the new triazole posaconazole and to six established antifungal agents by a modified NCCLS M27-A2 microdilution method and Etest; Velegraki A et al.; A novel formulation of RPMI 1640 medium for susceptibility testing of Malassezia yeasts by broth microdilution (BMD) and Etest is proposed . A modification of the NCCLS M27-A2 BMD method was used to test 53 isolates of Malassezia furfur (12 isolates), M . sympodialis (8 isolates), M . slooffiae (4 isolates), M . globosa (22 isolates), M . obtusa (2 isolates), M . restricta (2 isolates), M . pachydermatis (1 isolates), and M . dermatis (2 isolates) against amphotericin B, ketoconazole, itraconazole, fluconazole, voriconazole, terbinafine, and posaconazole by BMD and Etest . RPMI and antibiotic medium 3 (AM3) were supplemented with glucose, bile salts, a mixture of fatty acids, and n-octadecanoate fatty acids and Tween 20 . M . furfur ATCC 14521 and M . globosa ATCC 96807 were used as quality control strains . Depending on the species, MICs were read after 48 or 72 h of incubation at 32 degrees C . Low azole and terbinafine MICs were recorded for all Malassezia species, whereas amphotericin B displayed higher MICs (>/=16 microg/ml) against M . furfur, M . restricta, M . globosa, and M . slooffiae strains, which were AM3 confirmed . Agreement of the two methods was 84 to 97%, and intraclass correlation coefficients were statistically significant (P < 0.001) . Because of higher amphotericin B MICs provided by Etest for strains also displaying high BMD MICs (>/=1 microg/ml), agreement was poorer . The proposed media are used for the first time and can support optimum growth of eight Malassezia species for recording concordant BMD and Etest MICs.

J Clin Microbiol, 2004 Aug, 42(8), 3428 - 34
Suicide PCR on skin biopsy specimens for diagnosis of rickettsioses; Fournier PE et al.; As rickettsioses may be severe diseases and Rickettsia prowazekii is a potential agent of bioterrorism, highly efficient diagnostic techniques are required to detect rickettsiae in patients . We developed a nested PCR assay using single-use primers targeting single-use gene fragments present in the genomes of both Rickettsia conorii and R . prowazekii . We used this "suicide" PCR with DNA from 103 skin biopsy specimens from patients who definitely had a rickettiosis, 109 skin biopsy specimens from patients who possibly had a rickettsiosis, and 50 skin biopsy specimens from patients with nonrickettsial diseases . The suicide PCR detected "R . conorii conorii" in 38 biopsy specimens, R . africae in 28 biopsy specimens, R . slovaca in 12 biopsy specimens, "R . sibirica mongolotimonae" in 5 biopsy specimens, R . aeschlimannii in 2 biopsy specimens, and "R . conorii caspia" and "R . sibirica sibirica" in 1 biopsy specimen each . The technique had a specificity of 100% and a sensitivity of 68% . It was 2.2 times more sensitive than culture (P < 10(-2)) and 1.5 times more sensitive than regular PCR (P < 10(-2)) . The efficacy of the suicide PCR was reduced by antibiotic therapy prior to biopsy (P < 10(-2)) and was increased when it was performed with eschar biopsy specimens (P = 0.03) . We propose the use of the suicide PCR as a sensitive, specific, and versatile technique for improving the diagnosis of rickettsioses, especially when it is used on eschar biopsy specimens taken prior to antibiotic therapy.

J Chromatogr A, 2004 Jul 9, 1042(1-2), 15 - 22
Direct zonal liquid chromatographic method for the kinetic study of actinomycin-DNA binding; Vidal-Madjar C et al.; The binding of an anticancer drug (actinomycin D or ACTD) to double-stranded DNA (dsDNA) was studied by means of high-performance liquid chromatography (HPLC) . ACTD is an antitumor antibiotic containing one chromophore group and two pentapeptidic lactone cycles that binds dsDNA . Incubations of ACTD with DNA were performed at physiological pH . The complexed and free ligand concentrations of the mixture were quantified at 440 nm from their separation on a size-exclusion chromatographic (SEC) column using the same buffer for the elution and the sample incubation . The DNA and the ACTD-DNA complexes were eluted at the column exclusion volume while the ligand was retained on the support . An apparent binding curve was obtained by plotting the amount emerging at the exclusion column volume against that eluted at free ACTD retention volume . A dissociating effect was evidenced and the binding parameters were significantly different from those obtained at equilibrium by visible absorbance titration . The equilibrium binding parameters determined by absorption spectroscopy were used as starting data in the numerical simulations of the chromatographic process . The results showed a strong dependency of the apparent binding parameters on the reaction kinetics . Finally the comparison of the apparent binding curve obtained from the HPLC experiments and from the numerical simulations permitted an evaluation of the dissociation rate constant (kd = 0.004 s(-1)).

Int J Artif Organs, 2004 Jun, 27(6), 473 - 9
Elimination of linezolid by an in vitro extracorporeal circuit model; Schroeder TH et al.; Linezolid is an oxazolidinone antibiotic with activity against important grampositive aerobic bacteria, including nosocomial pathogens . It is not known whether dosage adjustments are necessary in patients treated with continuous renal replacement therapies . This in vitro study was conducted to investigate the elimination of linezolid in an in vitro continuous hemo(dia)filtration model using different filter materials (polysulfone, polyacrylonitrile, polyamide), surface areas, and different modes of renal replacement therapies . Linezolid was measured using HPLC with UV-detection . No adsorption of linezolid to any of the tested membranes was detected . Recovery of linezolid in the ultrafiltrate was 98.2 +/- 10.5% in the filtration mode . During dialysis, recovery was significantly less (87.6 +/- 16.1%; p = 0.02) . Linezolid elimination was not altered by filter size, when polysulfone filters with surface areas of 0.7 m2 and 1.3 m2 were tested . In conclusion, the dosage recommendations for linezolid are independent of the filter materials . However, the elimination is significantly higher during hemofiltration compared to dialysis.

J Biomed Mater Res, 2004 Sep 1, 70A(3), 467 - 79
Effect of biphasic calcium phosphates on drug release and biological and mechanical properties of poly(epsilon-caprolactone) composite membranes; Kim HW et al.; Poly(epsilon-caprolactone) (PCL) and biphasic calcium phosphate (CaP) composite membranes were prepared for use in tissue regeneration by a novel solvent casting-pressing method . An antibiotic drug, tetracycline hydrochloride (TCH), was entrapped within the membranes to investigate the efficacy of the material as a drug delivery system . The CaP powders were varied in amount (0-50 wt %) and in powder characteristics by heat treating at different temperatures, and their effects on the mechanical and biological properties and drug release of the membranes were examined . With CaP addition up to 30 wt %, the elastic modulus of the membranes was enhanced much due to the rigidity of CaP . While the tensile strength and elongation rate decreased gradually with CaP addition because the CaP powders acted as a failure source . The osteoblast-like cells cultured on the CaP-PCL composite membranes exhibited significant improvements in proliferation and alkaline phosphatase (ALP) activity compared to pure PCL and culture plastic control, indicating excellent cell viability and functional activity . The TCH drugs were released from the PCL and CaP-PCL membranes in a similar fashion; an initial burst followed by a reduced release rate . The initial burst effect diminished much by the addition of CaP powders . The CaP addition increased the drug release rate after an initial period, and this was attributed to the high water uptake capacity and dissolution of the CaP containing membranes . Compared to the composite membranes containing heat-treated CaP powders, those with as-precipitated ones had higher dissolution and drug releases . These observations on mechanical properties and cellular responses as well as on drug release profiles suggested that the CaP-PCL composite membranes are potentially applicable to tissue regeneration and drug delivery system .

Ophthalmic Res, 2004 Jul-Aug, 36(4), 183 - 94
Lachrymal determinations: methods and updates on biopharmaceutical and clinical applications; Dumortier G et al.; This article displays different procedures used to collect lachrymal fluid and describes some of its applications . Sampling tears represents the main difficulty to produce precise and reproducible results . The direct sampling procedure consists in collecting tears with capillary tubes and has the drawback of demanding previous stimulation that induces major dilution . The indirect method does not require preliminary stimulation but has been held responsible for altering epithelium and promoting leakage from plasma . Schirmer strips and sponges are classically required . Applications are numerous in biopharmaceutical and clinical fields . The determination of endogenous components has great potentiality as a diagnostic tool, but the use of tear as a substitute of plasma does not present clinical relevance . Levels of drugs like immunosuppressive or antibiotic agents are determined in tears to verify that pharmacological concentrations are reached and frequency of administration is deduced from kinetic fitting .

J Neurosurg Spine, 2004 Jul, 1(1), 80 - 6
Suspended laminoplasty for wide posterior cervical decompression and intradural access: results, advantages, and complications; Casha S et al.; OBJECT: Cervical laminoplasty is a recognized technique commonly used for multilevel posterior cervical decompression, and it is favored over laminectomy for maintaining spinal stability . Traditional hinge techniques, however, limit lateral exposure on one side and can limit dural exposure . The authors present their experience with a modified laminoplasty technique incorporating complete laminectomy and placement of titanium miniplate instrumentation . This method allows wide bilateral posterior decompression and unobscured dural access . METHODS: Twenty-eight patients (mean age 57 years) underwent cervical laminoplasty during a 4-year period . Twenty-seven patients presented with progressive cervical myelopathy . Seventeen patients (61%) had degenerative spondylotic stenosis; nine (32%) underwent resection of an intradural neoplasm . A mean of 3.5 levels were exposed and reconstructed . The follow-up period ranged from 4 months to 4 years (mean 15 months) . The mean angular extension-flexion displacement measured between C-1 and C-7 was unchanged postoperatively, with preserved mobility across laminoplasty-treated segments in all patients . The anteroposterior diameter of the spinal canal increased 3.6 mm (27.2%) postoperatively (p = 0.004) . In one patient an asymptomatic postoperative kyphosis developed . There were five cases of postoperative infection . One superficial infection resolved after intravenous antibiotic therapy alone, and four deep infections required surgical reexploration . CONCLUSIONS: The advantages of this technique over other laminoplasty methods include wide lateral spinal canal and intradural access, as well as preserved motion with partial restoration of the posterior tension band.

Eur J Haematol, 2004 Sep, 73(3), 219 - 22
Cytogenetic and hematological spontaneous remission in a case of acute myelogenous leukemia; Fozza C et al.; Several cases of spontaneous remission (SR) interrupting the invariably progressive course of untreated acute myeloblastic leukemia (AML) have been reported so far . We shall add to this series the hematological and cytogenetic SR occurring in a 72-yr-old man affected by AML following myelodysplastic syndrome . At diagnosis cytogenetic analysis showed the 48, xy, del (6) (p22-pter), +13, +14 karyotype . Owing to a lobar pneumonia, the chemotherapy was deferred and a broad spectrum antibiotic therapy was established . Supportive care included red cells and platelet transfusions and low-dose corticosteroid . Two months later, after the pneumonia had completely disappeared, a complete remission, lasting about 5 months, was documented on bone marrow morphological and cytogenetical examination, although some degree of myeloid dysplasia persisted . Possible mechanisms of the various SRs described during the course of AML are discussed with a review of the literature . Copyright Blackwell Munksgaard 2004.

Scand J Infect Dis, 2004, 36(5), 388 - 9
Fulminant endogene gas gangrene in a previously healthy male; Zelic M et al.; Spontaneous or non-traumatic gas gangrene is a rare condition . The present report refers to a previously healthy 57-y-old male who developed gas gangrene in the left lumbar region, left flank, left scapular, inguinal and suprapubic regions . Despite surgical, intensive care treatment, and antibiotic therapy, the patient died 32 h after the onset of the first symptoms.

Scand J Infect Dis, 2004, 36(5), 384 - 6
Endobronchial actinomycosis secondary to a tooth aspiration; Bergthorsdottir R et al.; We report a middle aged smoker with recurrent pneumonia caused by endobronchial actinomycosis secondary to a tooth aspiration . Unlike previously reported cases, our patient was not chronically debilitated . The case suggests that a follow-up bronchoscopy is beneficial after the initiation of antibiotic therapy for endobronchial actinomycosis.

Radiologe, 2004 Mar, 44(3), 242 - 53
{Imaging of bacterial infections of the sacroiliac joint}; Groves C et al.; Infection of the sacroiliac joint can be pyogenic or granulomatous and is usually unilateral . There are a number of predisposing conditions including drug abuse and intra articular steroid injection, but in 44% of cases, no definite predisposing factors can be identified . Considerable delay between presentation and diagnosis is recognized . The clinical picture may be non-specific and variable, and clinical suspicion may be low due to the relatively low incidence of the condition . This is compounded by difficulties in clinical examination of the SUs . The diagnosis is based on a history suggestive of infection, clinical or radiographic localization to the SUs, and a positive blood culture or joint aspirate . The pathology of pyogenic sacroiliitis is reviewed with respect to the anatomy of the SU, and the differential diagnoses considered . The imaging findings, and relative merits of all the modalities are discussed with particular consideration given to changes over the course of the disease . Imaging strategies are evaluated and proposed . As the commonest presenting symptom is low back pain, consideration should be given to the addition of a STIR sequence covering the SUs on all routine lumbar spine MR examinations . MR imaging is the most sensitive and specific imaging modality, while CT-guided arthrocentesis improves diagnostic confidence . Tc99MDP blood pool imaging mirrors the clinical features of resolution, and scintigraphy may be the best method to monitor response to treatment . Targeted antibiotic therapy usually leads to a full recovery . A high incidence of clinical suspicion, with MR imaging at an early stage are the essential prerequisites to an accurate diagnosis of bacterial sacroiliitis.

Pediatrics, 2004 Aug, 114(2), 435 - 42
Normal annual increase of bone mineral density during two years in patients with cystic fibrosis; Gronowitz E et al.; OBJECTIVES: To determine prospectively for 2 years the change in bone mineral density (BMD) in patients with cystic fibrosis (CF) and to correlate clinical data and routine biochemical parameters of bone metabolism and infection with BMD . METHODS: Fifty-four patients with CF, aged 6 to 33 years, were included . BMD was measured using dual-energy x-ray absorptiometry in lumbar spine (LS) and femoral neck (FN) . Anthropometric data and biochemical markers of bone metabolism and infection were measured . The number of intravenous antibiotic courses per year (ivAC) and pulmonary function were assessed . RESULTS: The patients had normal anthropometric data and normal growth, but 36% and 33% of the patients had BMD z score <-1 standard deviation in LS and in FN, respectively . Nevertheless, BMD increased at a normal rate during the 2 years and was correlated to weight and lung function . Intact parathyroid hormone was positively correlated with the increase of BMD in both LS and FN during childhood . Blood sedimentation rate, serum concentration of immunoglobulin G, and ivAC were negatively correlated with BMD in FN . Patients with 2 more severe CF transmembrane conductance regulator mutations had significantly lower BMD in FN than other genetic combinations . CONCLUSION: The study suggests that low BMD in CF is multifactorial and depends on infection and nutritional parameters . Differences in BMD of LS and FN suggested higher susceptibility to infection in FN at all ages . Longitudinal studies starting early before bacterial colonization would be valuable to determine the relative role of infection in the development of BMD in CF.

J Laryngol Otol, 2004 Jun, 118(6), 439 - 42
Use of steroids in the treatment of peritonsillar abscess; Ozbek C et al.; Peritonsillar abscess is the most common deep infection of the head and neck that occurs in adults; the treatment of the disease remains controversial . A prospective study using a single high dose steroid treatment for peritonsillar abscess, was undertaken in 62 patients to determine the treatment's effectiveness in relieving symptoms such as fever, throat pain, dysphagia and trismus . All patients were randomly assigned to two groups: 28 patients received intravenous antibiotic therapy and a single dose placebo and 34 patients were treated with single use of high dose steroid in addition to intravenous antibiotic . Patients were hospitalized after needle aspiration and therefore their clinical courses and responses to therapy could be rigorously assessed . Comparison of clinical outcomes with respect to hours hospitalized, throat pain, fever, trismus were assessed between the two groups . Clinical outcomes revealed a statistically significant difference between the two groups (p < 0.01), indicating that single use of high dose steroid prior to antibiotic therapy is more effective than the use of an antibiotic alone . These results suggest that single intravenous use of steroid in addition to antibiotic therapy is an excellent choice for the management of peritonsillar abscess.

Dig Liver Dis, 2004 Jul, 36(7), 455 - 60
Helicobacter pylori impairs iron absorption in infected individuals; Ciacci C et al.; BACKGROUND: Infection with Helicobacter pylori is recognised as a major risk factor for chronic gastritis, peptic ulcer disease and gastric cancer . The association between H . pylori infection and iron deficiency anaemia has been established . Multiple mechanisms have been advocated to explain the relationship between H . pylori and iron status and their association might reduce iron deposit . AIM: Aim of this study was to investigate whether H . pylori infection affects iron absorption . METHODS: The study was designed on a prospective basis . Fifty-five subjects underwent upper gastrointestinal endoscopy and biopsy to investigate the presence of H . pylori and, when this was positive, also search of serum anti-CagA was performed . Tests included an oral iron absorption test with the administration of 1 mg/kg of Fe2+ . Iron levels were measured before and 2 h after iron administration (delta iron) . H . pylori-positive subjects were administered antibiotic therapy for 1 week and, 2 months later, the oral iron absorption test was repeated and urea-breath test was first performed . RESULTS: H . pylori-positive subjects had lower serum level of ferritin and lower delta iron compared to H . pylori-negative subjects . That difference is significant in anaemic women and is independent of the presence of serum anti-CagA antibodies . After H . pylori eradication iron absorption test was similar to those of non-infected subjects . CONCLUSION: H . pylori infection impairs iron uptake . That mechanism, together with others, may contribute to the depletion of iron in infected patients.

Antibiot Khimioter, 2004, 49(2), 3 - 7
{Rifampicin use for potency stabilization in Rif(r) mutants of Streptomyces recifensis subsp . lyticus, an organism producing lytic enzymes}; Zhernosekova IV et al.; Rif(r) mutants 1P-92 and 2P-15 were isolated as a result of selection of Streptomyces recifensis subsp . lyticus, an organism producing lytic enzymes . The effect of rifampicin on the biosynthetic potency of the mutants was studied . When added to the medium for cultivation of Rif(r) mutants 1P-92 and 2P-15 in the optimal concentrations (7.5 and 10.0 mcg/ml respectively), the antibiotic showed stabilizing effect on their potency in successive subcultures and recovered the initial potency of the old laboratory strains . Preliminary cultivation of strain 2P-15 after its storage for 6 years at a temperature of -20 degrees C made it possible to increase the efficiency of the initial potency recovery in the analytical selection.

G Ital Nefrol, 2004 May-Jun, 21(3), 254 - 8
{When the history of nephrology changed that of medicine}; Capodicasa E et al.; Medicine owes much to nephrology . Indeed many of the practical and doctrinal acquisitions, through nephrology have derived their first intuitions, explanations and applications which have become epochal conquests of scientific progress . This article is a historical reconstruction of six of the milestones which have marked the medical and scientific human progress: Galeno, the ligature of the ureters and the birth of experimental medicine; uroscopy and the introduction of laboratory exams; the synthesis of urea in the laboratory and the beginnings of biothecnology; the kidney and the introduction of systematic parenteral antibiotic therapy; the kidney and the first artificial organs; the kidney and the start of the transplantation era.

Maturitas, 2004 Aug 20, 48(4), 372 - 80
Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy; Petri Nahas E et al.; OBJECTIVE: To evaluate the effects of isoflavones on vasomotor symptoms and blood lipids in postmenopausal women with contraindication for conventional hormone replacement therapy (HRT) . METHODS: This prospective, double-blind and placebo-controlled study included 50 postmenopausal women randomly divided into two groups: 25 women on soy germ isoflavones (60 mg per day, capsules) and 25 women on placebo . Inclusion criteria included: non-vegetarian, non-asian women whose last menstruation dated at least 12 months prior to the beginning of the study, with FSH > 40 mIU/ml, hot flushes and contraindication for HRT, not using tamoxifen or antibiotic and no disease of the gastrointestinal tract . For 6 months, the Kupperman menopausal index (KMI), the vaginal cytological maturation value (MV) and both hormonal and lipid profiles were assessed . The t-test and analysis of variance (ANOVA) were employed to compare the two groups . RESULTS: In both groups, a decreased KI rate was observed . However, isoflavone was significantly superior to placebo in reducing hot flushes (44% versus 10%, respectively) (P < 0.05) . After 6 months, the isoflavone group showed increased estradiol levels with unchanged FSH, LH, and vaginal cytology, and a reduction of 11.8% in LDL and an increase of 27.3% in HDL (P < 0.05 ) . In the placebo group, just a reduction in MV was observed after 6 months (P < 0.05 ) . CONCLUSIONS: Soy germ isoflavone exerted favorable effects on vasomotor symptoms and lipid profile, showing itself to be an interesting alternative therapy for the postmenopausal women with contraindication for conventional HRT.

Sociol Health Illn, 2004 Jul, 26(5), 617 - 44
The use of technology at home: what patient manuals say and sell vs . what patients face and fear; Lehoux P et al.; Over the past 15 years, the use of specialised medical equipment by patients at home has increased in most industrialised countries . Adopting a conceptual framework that brings together two research perspectives, i.e . the sociology of technology and the sociology of illness, this paper empirically examines why and how patients use health technology at home and in the broader social world . Our study compares and contrasts the use of four interventions: antibiotic intravenous therapy, parenteral nutrition, peritoneal dialysis and oxygen therapy . We conducted interviews with patients (n = 16) and caregivers (n = 6), and made direct observations of home visits by nurses (n = 16) . The content and structure of patient manuals distributed by major manufacturers and hospitals were analysed (n = 26) . The aim of our study was to determine how technology was supposed to be used versus how it was actually used . This study shows that patients are deeply ambivalent about the benefits and drawbacks of technology, and that these advantages and disadvantages are shaped by the various places in which the technology is used . While technology can be pivotal in making patients autonomous and able to participate in the social world, it also imposes heavy restrictions that are intimately interwoven with the nature of the particular disease and with the patient's personal life trajectory.

Biotechnol Appl Biochem, 2005 Feb, 41(Pt 1), 17 - 28
Batch cooling crystallization and pressure filtration of sulphathiazole: the influence of solvent composition; Hakkinen A et al.; Currently there is a great interest in new process analytical approaches to increase the process understanding of pharmaceutical unit operations . In the present study, the influence of the solvent composition on the material properties and, further, on the filtration characteristics, of different crystal suspensions obtained through an unseeded batch-cooling-crystallization process was studied . Sulphathiazole, which is an antibiotic agent with multiple polymorphic forms, was produced by performing laboratory-scale cooling crystallization experiments from five different mixtures of water and propan-1-ol (n-propanol) . The size, shape and polymorphic composition of the crystals produced were characterized with a scanning electron microscope, with a novel automated image analyser and with an X-ray powder diffractometer . All of the monitored crystal properties were found to clearly differ between the samples obtained from different solvents . The crystals produced in the batch-cooling-crystallization experiments were separated from the crystallizing solvents using a batch-type pressure Nutsche filter, and the filtration characteristics of the suspensions were evaluated on the basis of average filter-cake porosities and average specific cake resistances, which were determined from the experimentally obtained filtration data . Comparison between the calculated filtration characteristics revealed that considerable differences existed between the different suspensions, and it could therefore be concluded that the pressure-filtration process was influenced by the composition of the crystallizing solvent . The filterability of all the studied sulphathiazole suspensions was considered to be rather good on the basis of the relatively low cake porosities (0.51-0.63), which were accompanied with low average specific cake resistances {(8.7x10(7))-(1.2x10(9)) m/kg}.

Arch Pharm Res, 2004 Jun, 27(6), 640 - 5
Antiproliferative effect of trichostatin A and HC-toxin in T47D human breast cancer cells; Joung KE et al.; Histone deacetylase inhibitors are new class of chemotherapeutic drugs able to induce tumor cell apoptosis and/or cell cycle arrest . Trichostatin A, an antifungal antibiotic, and HC-toxin are potent and specific inhibitors of histone deacetylase activity . In this study, we have examined the antiproliferative activities of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer, T47D cells . Both trichostatin A and HC-toxin showed potent antiproliferative efficacy and cell cycle arrest at G2/M in T47D human breast cancer cells in a dose-dependent manner . Trichostatin A caused potent apoptosis of T47D human breast cancer cells and trichostatin A-induced apoptosis might be involved in an increase of caspase-3/7 activity . HC-toxin evoked apoptosis of T47D cells and HC-toxin induced apoptosis might not be mediated through direct increase in caspase-3/7 activity . We have identified potent activities of antiproliferation, apoptosis, and cell cycle arrest of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer cell line T47D.

Nippon Rinsho, 2004 Jul, 62(7), 1325 - 31
{Imatinib therapy for patients with chronic myelogenous leukemia}; Kawai Y et al.; Imatinib mesylate (imatinib), a selective inhibitor of BCR-ABL tyrosine kinase, has shown excellent efficacy in patients with chronic myelogenous leukemia (CML) in the chronic phase, however, it does not in those in the accelerated phase or blastic crisis . In patients with CML who have undergone allogeneic stem cell transplantation, imatinib has the capability to induce hematological and even molecular response, and provides a prolonged survival among those in the chronic and accelerated phases . It has been demonstrated that major cytogenic response is a surrogate marker for survival in cases receiving imatinib . It has also been demonstrated that a genome-wide cDNA microarray enables the prediction of sensitivity to imatinib . The acquired resistance in patients who failed to respond to imatinib seemed to be induced by several point mutations in the BCR-ABL gene, which were likely to affect the binding of imatinib with BCR-ABL . Polyclonal cells which harbor distinct mutations in a single patient seemed to be selected in vivo under the selective pressure of imatinib, indicating the rationale of combined treatment with other types of agents . Recently, SPIRIT (STI571 Prospective International Randomized Trials) have been conducted, in which the efficacy of imatinib monotherapy, and imatinib combined with interferon or cytarabine were compared . New agents which inhibit the signaling pathway related to BCR-ABL, such as adaphostin (NSC680410), farnesyltransferase inhibitor SCH66336, MAP kinase inhibitor PD184352, PD98059, U0126, and antibiotic geldanamycin, have shown excellent activity combined with imatinib in vitro.

Arzneimittelforschung, 2004, 54(6), 320 - 2
Ceftazidime determination in serum by high-pressure liquid chromatography; Humbert T et al.; A rapid and sensitive high-pressure liquid chromatographic method with simple sample preparation was developed for the quantitative analysis of the beta-lactam antibiotic ceftazidime (CAS 78439-06-2, Fortum) . A good linear relationship was established between the peak area and the amount of ceftazidime injected over a concentration range of 1 to 200 microg/ml . The detection limit of the method was calculated to be 0.9 microg/ml . Stability was shown at 4 degrees C and at -196 degrees C for time periods of 2 h and 84 days, respectively.

J Environ Pathol Toxicol Oncol, 1999, 18(3), 147 - 58
Antimutagenic/antioxidant activity of green tea components and related compounds; Pillai SP et al.; The ability of green tea components and other antioxidant compounds to function as antimutagens/antioxidants has been well established, and their role in cancer prevention is supported by numerous epidemiological studies . We have utilized modified Ames tests, superoxide scavenging assays, and assays for protection against DNA scissions to compare and contrast the protective effects of various teas and commercial and laboratory-isolated tea components to those produced by compounds such as resveratrol, selenium, curcumin, vitamins C and E, quercetin dihydrate, sulforaphane, ellagic acid dihydrate, glutathione reduced, trolox, butylated hydroxanisole (BHA), butylated hydroxytoluene (BHT), and N-acetyl-L-cysteine (NAC) . In Ames tests, employing hydrogen peroxide as a mutagen, epigallocatechin gallate (EGCG) produced the highest level of protection of all antioxidants tested . Measurement of protection against DNA scissions produced results that again showed that EGCG produced the strongest protective effects . In scavenging assays using a xanthine-xanthine oxidase (enzymatic system), epicatechin gallate (ECG) showed the highest scavenging potential . In a nonenzymatic (phenazine methosulfate-NADH) oxidizing system, EGCG once again showed the strongest effects . The implications of these and similar results are discussed in relation to cancer prevention and prevention of drug/antibiotic resistance.

Laryngoscope, 2004 Aug, 114(8), 1403 - 5
Nasopharyngeal actinomycosis: a rare cause of nasal airway obstruction; Daamen N et al.; Nasopharyngeal actinomycosis is a rare clinical disease . It can occur after nasal trauma or surgical manipulation . It is also reported to occur without prior trauma, making diagnosis difficult . We report a case of nasopharyngeal actinomycosis that presented as nasal airway obstruction causing snoring and mimicking nasopharyngeal carcinoma . To our knowledge, only a few other cases of nasopharyngeal actinomycosis have previously been published, most coming after mucosal trauma . Diagnosis is made by observing the bacteria or its associated sulfur granules in the biopsy specimen . This anaerobic organism is difficult to culture . Treatment consists of wide debridement and prolonged antibiotic therapy, with good prognosis.

Genetics, 2004 Jul, 167(3), 1155 - 64
Genetic transformation of Neurospora tetrasperma, demonstration of repeat-induced point mutation (RIP) in self-crosses and a screen for recessive RIP-defective mutants; Bhat A et al.; The pseudohomothallic fungus Neurospora tetrasperma is naturally resistant to the antibiotic hygromycin . We discovered that mutation of its erg-3 (sterol C-14 reductase) gene confers a hygromycin-sensitive phenotype that can be used to select transformants on hygromycin medium by complementation with the N . crassa erg-3+ and bacterial hph genes . Cotransformation of hph with PCR-amplified DNA of other genes enabled us to construct strains duplicated for the amplified DNA . Using transformation we constructed self-fertile strains that were homoallelic for an ectopic erg-3+ transgene and a mutant erg-3 allele at the endogenous locus . Self-crosses of these strains yielded erg-3 mutant ascospores that produced colonies with the characteristic morphology on Vogel's sorbose agar described previously for erg-3 mutants of N . crassa . The mutants were generated by repeat-induced point mutation (RIP), a genome defense process that causes numerous G:C to A:T mutations in duplicated DNA sequences . Homozygosity for novel recessive RIP-deficient mutations was signaled by self-crosses of erg-3-duplication strains that fail to produce erg-3 mutant progeny . Using this assay we isolated a UV-induced mutant with a putative partial RIP defect . RIP-induced mutants were isolated in rid-1 and sad-1, which are essential genes, respectively, for RIP and another genome defense mechanism called meiotic silencing by unpaired DNA.

J Matern Fetal Neonatal Med, 2004 Apr, 15(4), 275 - 8
Placenta increta; conservative management -- a successful outcome . Case report and literature review; Adair SR et al.; Placenta increta, a rare complication of pregnancy, is associated with significant postpartum hemorrhage often requiring emergency hysterectomy . We report a case of conservative management, with a combination of parenteral methotrexate, serial ultrasound and Doppler assessment, followed by interval manual removal of placenta.

Curr Top Med Chem, 2004, 4(11), 1115 - 26
LPS signal transduction: the picture is becoming more complex; Diks SH et al.; Lipopolysaccharide (LPS) is the principal initiator of septic shock and it is to a large extent responsible for post-operative mortality . The use of antibiotics is still the most successful therapy against infection that may lead to sepsis and septic shock . With the advent of antibiotic resistant strains like MRSA the usefulness of conventional antibiotics is declining and new treatment strategies for LPS-mediated septic shock are called for . In this review we discuss the molecular mechanisms that are involved in the recognition of LPS and in the initiation of an immune response . Furthermore, we also review the recent insights in the signal transduction including receptor clustering and signalosome activation . Further insight into LPS-dependent signal transduction will assist the development of novel rational therapy.

Arch Gynecol Obstet . 2004 Jul 23; {Epub ahead of print}
Tocolysis with atosiban: experience in the management of premature labor before 24 weeks of pregnancy; Richter ON et al.; OBJECTIVE . Atosiban has been shown to be an effective tocolytic agent with a low rate of side effects during 24 to 33 weeks of gestation . Atosiban acts through selective, competitive inhibition of both oxytocin and vasopressin, so that there are reasons to assume that a tocolytic effect can also be achieved earlier in the pregnancy . STUDY DESIGN . In this prospective, randomized pilot study, 20 women in the 18th through 24th week of gestation who presented at our hospital with preterm labor were treated with atosiban . In the control group 20 women received saline infusions . All patients received antibiotic therapy . A cervical cerclage was performed when indicated as was correction of the vaginal pH . RESULTS . The tocolytic effect began after 3-10 min (median: 6.5 min) . Treatment time until the complete absence of contractions was 3-12 h (median: 7.5 h) . Pregnancies were prolonged between 11.1 and 21.7 weeks (median: 15.6 weeks) in the atosiban group vs . 10.5-19.1 weeks in the control group . If well tolerated, atosiban was continued . There were no significant alterations in the routine laboratory parameters, circulation parameters, and fluid balance . CONCLUSION . In summary, atosiban showed itself to be effective for tocolytic treatment for premature labor, even during 18 and 24 weeks of pregnancy, while exhibiting its known, favorable profile of side effects.

Pediatr Radiol, 2004 Dec, 34(12), 933 - 42 Epub 2004 Dec.
Complications of pediatric paranasal sinusitis; Reid JR; Acute paranasal sinus infection in children is often diagnosed clinically without the need for radiographic confirmation . Most cases have a favorable outcome following appropriate antibiotic therapy . A small percentage of cases where symptoms and signs are persistent or severe will require emergent imaging to rule out complications related to local spread of disease intraorbitally or intracranially . A strong index of suspicion is required in such cases, and cross-sectional imaging evaluation with CT and MRI should include axial and coronal images of the paranasal sinuses and, where appropriate, the orbits and brain (with attention to the cavernous sinus) . There is no role for plain radiography in the evaluation of the complications of acute sinusitis in the pediatric patient.

Rev Clin Esp, 2004 Jul, 204(7), 351 - 4
{Evolution of serological characteristics in 26 patients with tularemia three years after the outbreak}; Martin-Serradilla JI et al.; INTRODUCTION: Tularemia was an unknown zoonosis in our region until the first quarter of 1998 . The outbreak that took place on those dates has made possible to study some scantly known characteristics of the disease, as are the determinants for the persistence of a high antibody titer . MATERIAL AND METHODS: Between March and May, 2001, a clinical-analytical control was carried out in 26 patients who showed tularemia in the first quarter of 1998 . RESULTS: The clinical forms during the acute phase were: ulceroglandular (46.2% of patients), nodal (26.9%), typhoid (15.4%) and pharyngeal (11.5%) . Antibiotics most prescribed were streptomycin and doxycycline . Nine patients showed sequelae three years later . The arithmetical mean of antibody titer declined from 1/1011 in 1998 to 1/187 in 2001 . 76.92% of the patients maintained an antibody titer equal or higher than 1/160 three years after the acute phase . A significant relation between the initial antibody titer and the antibody titer registered in the late phase was observed . A relationship between final antibody titer and prescribed antibiotic, presence of sequelae, gender, or age was not demonstrated . CONCLUSIONS: The antibody titer in the presence of Francisella tularensis is high in an important percentage of the patients along years . We should reconsider the standard diagnostic criteria to our community, accepting as a certainty diagnosis exclusively the presence of a demonstrative culture or the existence of seroconversion.

Aliment Pharmacol Ther, 2004 Aug 1, 20(3), 333 - 8
Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis; Russo A et al.; BACKGROUND: KC 11458, a motilin agonist without antibiotic properties, accelerates gastric emptying in animals and healthy humans . AIM: To evaluate the acute effects of KC 11458 on gastric emptying in diabetic gastroparesis . METHODS: Twenty-nine patients (6 type 1 and 23 type 2) with gastroparesis underwent assessments of: (i) gastric emptying of a solid/liquid meal using scintigraphy, (ii) glycaemic control (blood glucose at 0, 30, 60, 90 and 120 min during the gastric emptying measurement) and (iii) upper gastrointestinal and 'meal-related' symptoms (questionnaire), at baseline and after treatment with KC 11458 in a dose of 8 mg t.d.s., or placebo for 8 days . RESULTS: KC 11458 had no statistically significant or clinically relevant effect on gastric emptying of either the solid intragastric retention at 100 min (T100) (P = 0.87) or liquid 50% emptying time (T50) (P = 0.17) components of the meal . KC 11458 slightly worsened (P = 0.04) upper gastrointestinal symptoms when compared with placebo . The magnitude of the change in solid gastric emptying correlated with the change in the blood glucose concentration (r = 0.49; P < 0.05) . CONCLUSIONS: KC 11458, in a dose of 8 mg t.d.s . for 8 days, does not accelerate gastric emptying in patients with diabetic gastroparesis . The absence of efficacy may relate to an effect of hyperglycaemia.

Electrophoresis, 2004 Jul, 25(14), 2292 - 8
Capillary electrophoresis analysis of fosfomycin in biological fluids for clinical pharmacokinetic studies; Petsch M et al.; A feasible capillary zone electrophoresis (CZE) method with indirect UV and contactless conductivity detection was developed for the determination of fosfomycin, an antibiotic, in human plasma and microdialysis samples . Samples were collected from test persons during a clinical trial . The background electrolytes used consisted of 25 mM benzoic acid and 0.5 mM hexadecyltrimethylammonium bromide, adjusted with tris(hydroxymethyl)aminomethane solution to pH 6.95 for plasma, and to pH 8.05 for microdialysis samples . CZE separations of the anionic analyte were carried out with reversed electroosmotic flow directed towards the anode . The limit of detection was between 0.6 and 2 microg/mL, depending on the matrix and the detection method . No sample preparation was needed for microdialysis samples; for plasma samples, proteins were precipitated with methanol (1+2, v+v), and the supernatant was analyzed . The yield determined with spiked samples was about 100%, the reproducibility of the entire method, expressed by the RSD% of three independent determinations of fosfomycin in triplicate after spiking Ringer's solutions and plasma samples, respectively, was better than 8% . The method is thus well-suited for clinical studies for the determination of the antibiotic in biological fluids.

RNA, 2004 Sep, 10(9), 1459 - 68 Epub 2004 Jul 23.
Ligand-induced changes in 2-aminopurine fluorescence as a probe for small molecule binding to HIV-1 TAR RNA; Bradrick TD et al.; Replication of human immunodeficiency virus type 1 (HIV-1) is regulated in part through an interaction between the virally encoded trans-activator protein Tat and the trans-activator responsive region (TAR) of the viral RNA genome . Because TAR is highly conserved and its interaction with Tat is required for efficient viral replication, it has received much attention as an antiviral drug target . Here, we report a 2-aminopurine (2-AP) fluorescence-based assay for evaluating potential TAR inhibitors . Through selective incorporation of 2-AP within the bulge (C23 or U24) of a truncated form of the TAR sequence (delta TAR-ap23 and delta TAR-ap24), binding of argininamide, a 24-residue arginine-rich peptide derived from Tat, and Neomycin has been characterized using steady-state fluorescence . Binding of argininamide to the 2-AP deltaTAR constructs results in a four- to 11-fold increase in fluorescence intensity, thus providing a sensitive reporter of that interaction (KD approximately 1 mM) . Similarly, binding of the Tat peptide results in an initial 14-fold increase in fluorescence (KD approximately 25 nM), but is then followed by a slight decrease that is attributed to an additional, lower-affinity association(s) . Using the deltaTAR-ap23 and TAR-ap24 constructs, two classes of Neomycin binding sites are detected; the first molecule of antibiotic binds as a noncompetitive inhibitor of Tat/argininamide (KD approximately 200 nM), whereas the second, more weakly bound molecule(s) becomes associated in a presumably nonspecific manner (KD approximately 4 microM) . Taken together, the results demonstrate that the 2-AP fluorescence-detected binding assays provide accurate and general methods for quantitatively assessing TAR interactions.

Infect Immun, 2004 Aug, 72(8), 4541 - 51
Icm/dot-independent entry of Legionella pneumophila into amoeba and macrophage hosts; Bandyopadhyay P et al.; Legionella pneumophila, the causative agent of Legionnaires' disease, expresses a type IVB secretion apparatus that translocates bacterial proteins into amoeba and macrophage hosts . When stationary-phase cultures are used to infect hosts, the type IVB apparatus encoded by the icm/dot genes is required for entry, delay of phagosome-lysosome fusion, and intracellular multiplication within host cells . Null mutants with mutations in icm/dot genes are defective in these phenotypes . Here a new model is described in which hosts are infected with stationary-phase cultures that have been incubated overnight in pH 6.5 buffer . This model is called Ers treatment because it enhances the resistance to acid, hydrogen peroxide, and antibiotic stress beyond that of stationary-phase cultures . Following Ers treatment entry into amoeba and macrophage hosts does not require dotA, which is essential for Legionella virulence phenotypes when hosts are infected with stationary-phase cultures, dotB, icmF, icmV, or icmX . Defective host entry is also suppressed for null mutants with mutations in the KatA and KatB catalase-peroxidase enzymes, which are required for proper intracellular growth in amoeba and macrophage hosts . Ers treatment-induced suppression of defective entry is not associated with increased bacterial adhesion to host cells or with morphological changes in the bacterial envelope but is dependent on protein expression during Ers treatment . By using proteomic analysis, Ers treatment was shown to induce a protein predicted to contain eight tetratricopeptide repeats, a motif previously implicated in enhanced entry of L . pneumophila . Characterization of Ers treatment-dependent changes in expression is proposed as an avenue for identifying icm/dot-independent factors that function in the entry of Legionella into amoeba and macrophage hosts.

Chem Biol, 2004 Jul, 11(7), 959 - 69
The hedamycin locus implicates a novel aromatic PKS priming mechanism; Bililign T et al.; The biosynthetic gene cluster for the pluramycin-type antitumor antibiotic hedamycin has been cloned from Streptomyces griseoruber . Sequence analysis of the 45.6 kb region revealed a variety of unique features such as a fabH homolog (KSIII), an acyltransferase (AT) gene, a set of type I polyketide synthase (PKS) genes, and two putative C-glycosyltransferase genes . As the first report of the cloning of the biosynthetic gene cluster for the pluramycin antibiotics, this work suggests that the biosynthesis of pluramycins utilize an iterative type I PKS system for the generation of a novel starter unit that subsequently primes the type II PKS system . It also implicates the involvement of a second catalytic ketosynthase (KSIII) to regulate this unusual priming step . Gene disruption is used to confirm the importance of both type I and II PKS genes for the biosynthesis of hedamycin.

J Am Geriatr Soc, 2004 Aug, 52(8), 1373 - 7
The identification of genetically related bacterial isolates using pulsed field gel electrophoresis on nursing home units: a clinical experience; Drinka PJ et al.; OBJECTIVES: To describe a laboratory-based technique to track nursing home infections . DESIGN: Retrospective data analysis . SETTING: A 721-bed skilled care facility with 14 nursing units . PARTICIPANTS: Residents in a nursing home, average age 76+/-10, 78% male . MEASUREMENTS: Bacterial isolates were listed for each nursing unit . Clusters of identical species and antibiotic susceptibility were identified followed by pulsed-field gel electrophoresis (PFGE) . If the genetic analysis yielded related strains, the director of nursing performed a clinical investigation . PFGE is available through reference laboratories at a cost of approximately 75 dollars/isolate . RESULTS: Twenty-four clinical clusters of phenotypically identical bacteria (species, antibiotic susceptibility) were identified . Fourteen included genetically related isolates . CONCLUSION: Approximately half of the phenotypically identical clusters contained genetically related isolates . The identification of genetically related bacterial isolates on nursing units by PFGE provides staff with a specific circumstance to review secretion precautions . Genetic analysis may also demonstrate that apparent clusters are unrelated.

Arch Esp Urol, 2004 May, 57(4), 438 - 40
{Conservative treatment of a seminal vesicle abscess . Report of one case}; Madrid Garcia FJ et al.; OBJECTIVE: To describe the clinical conditions, the radiological findings and the management of a case of seminal vesicle abscess . METHODS: A 47-year old man presented with irritative voiding symptoms, fever, diminished ejaculated volume, hematuria and testicular pain . Diagnosis was made with digital rectal examination, ultrasound and CT . RESULTS: The patient was managed with antibiotic therapy alone for 4 weeks . Clinical and radiological resolution was achieved . CONCLUSIONS: Seminal vesicle abscess is a rare condition . Diagnosis is based on clinical data and radiological findings . Conservative treatment could be effective in selected cases.

FEMS Microbiol Lett, 2004 Aug 1, 237(1), 73 - 7
The LIV-I/LS system as a determinant of azaserine sensitivity of Escherichia coli K-12; Koyanagi T et al.; The growth of Escherichia coli is inhibited by an antibiotic compound, azaserine (O-diazoacetyl-L-serine) . Previous studies revealed the biochemical properties of azaserine, which involves inhibition of various enzymatic reactions as well as introduction of DNA breakage . However, genetically, nothing has been elucidated except that all the azaserine-resistant strains isolated so far carry lesions in the aroP gene as a primary determinant . Here, we demonstrate that, in addition to AroP, the LIV-I/LS system, an ATP-binding cassette type transporter, is involved in azaserine sensitivity of E . coli, by genetic analysis and transport studies, in which Ki value for azaserine was determined to be approximately 10(-3) M.

Bone, 2004 Aug, 35(2), 471 - 8
Chemically modified tetracyclines act through multiple mechanisms directly on osteoclast precursors; Holmes SG et al.; Chemically modified tetracyclines (CMTs) are thought to inhibit bone resorption primarily through their ability to inhibit matrix metalloproteinases (MMPs) . We have previously demonstrated that some tetracycline compounds (TCs) induce apoptosis in mature rabbit osteoclasts and inhibit osteoclastic resorption in mouse osteoblast/marrow co-cultures in vitro . In this report, we now show that non-antibiotic analogues of doxycycline (CMT-3) and minocycline (CMT-8) are potent inhibitors of osteoclastogenesis in vitro from human peripheral blood mononuclear cells (PBMC) stimulated with macrophage colony stimulating factor (MCSF) and receptor activator of NF-kappaB ligand (RANKL), through an action that is independent of osteoblast-osteoclast interactions . Osteoclast formation over 20 days was completely abrogated when CMT-3 or CMT-8 were included in PBMC cultures at a concentration of 250 ng/ml, although doxycycline at this concentration reduced osteoclast formation to ca . 50% of control . CMT-3 and CMT-8 also significantly induced apoptosis over 24 h in mature osteoclasts generated over 20 days when added to cultures at 5 microg/ml or more . In a time-course experiment, apoptosis was evident after a delay of 1-2 h following treatment of mature osteoclasts with CMT-3 at 20 microg/ml . The broad-spectrum MMP inhibitor BB94 (Batimastat) did not recapitulate the apoptosis induced by CMT-3, even at a concentration where MMP-13 activity was completely inhibited . There was no evidence for an anabolic effect of any of the TCs on osteoblast lineage cells in a calcifying fibroblastic colony (CFU-f) formation assay, where CMT-3 partially inhibited CFU-f formation at 5 microg/ml . Our data indicate that inhibition of osteoclast formation and induction of osteoclast apoptosis are pharmacologically significant actions of CMTs in inhibiting bone resorption, and that osteoclast apoptosis cannot be attributed to the ability of CMTs to inhibit MMPs or to actions mediated by osteoblastic lineage cells.

Expert Opin Investig Drugs, 2004 Aug, 13(8), 903 - 32
Novel modes of antifungal drug administration; Arthur RR et al.; Administration of antifungals by routes other than that for which the agent was designed or approved have been utilised in attempts to provide directed therapy, reduce adverse effects and improve drug penetration into selected infection sites, such as the central nervous system, lungs and peritoneum . The most widely investigated agent utilising a novel method of drug delivery is amphotericin B . Dose forms for this agent include topicals (aerosol, nasal spray, irrigations, pastes, absorbable sponges, impregnated bone cement and gelatin), oral dosage forms (solutions, suspensions, tablets and so on) and ophthalmic preparations (drops, ointments and injections) . Amphotericin B has been administered by routes such as oral, endobronchial, intrathecal, intracisternal, intra-articular, intraperitoneal, ophthalmic and as an antibiotic 'line lock' . Nystatin has been administered as an aerosol, percutaneous paste and bladder washes . Azoles, such as miconazole, fluconazole, ketoconazole and posaconazole, have been administered by novel methods but to a lesser degree . Most of these reports involve miconazole . The dose forms and routes of administration for azoles have included irrigants (bladder, joint), ophthalmic preparations (eye drops, intraocular injections, ointments), impregnated bone cement, endobronchial and intrathecal administration . Finally, both methylene blue (bladder washes) and flucytosine (peritoneal lavage, ophthalmic eye drops) have also been employed . Adequate evaluations of both the safety and efficacy of these therapies are most often hindered by prior or concomitant antifungal therapies, comorbidities and the lack of controlled clinical trials . In addition, the availability of newer treatment options, which demonstrate significant improvement in drug distribution and treatment-related adverse effects make many such novel modes of administration less practical or necessary . In contrast, the inhalation of antifungal aerosols, such as amphotericin B, is rapidly becoming a viable prophylactic option.

Cochrane Database Syst Rev . 2004;(3):CD004425.
Combined oral contraceptive pills for treatment of acne; Arowojolu AO et al.; BACKGROUND: Acne is a common skin disorder among women . Although no uniform approach to the management of acne exists, combination oral contraceptives (COCs), which contain an estrogen and a progestin, often are prescribed for women . OBJECTIVES: To determine the effectiveness of COCs for the treatment of facial acne compared to placebo or other active therapies . SEARCH STRATEGY: We searched the computerized databases Cochrane Skin Group trial register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, Biological Abstracts and LILACS for randomized controlled trials of COCs and acne . We wrote to authors of identified trials to seek any unpublished or published trials that we might have missed . SELECTION CRITERIA: All randomized controlled trials reported in any language that compare the effectiveness of a COC containing an estrogen and a progestin to placebo or another active therapy for acne in women were eligible . DATA COLLECTION AND ANALYSIS: We extracted data on total and specific (i.e . open or closed comedones, papules, pustules and nodules) facial lesion counts; acne severity grades; global assessments by the clinician or the participant and discontinuation due to adverse events . Data were entered and analyzed in RevMan 4.2 . MAIN RESULTS: The search yielded five placebo-controlled trials that made three different comparisons and 14 trials that made nine comparisons between two COC regimens . An additional trial compared a COC to an antibiotic . COCs reduced acne lesion counts, severity grades and self-assessed acne compared to placebo . Differences in the comparative effectiveness of COCs containing varying progestin types and dosages, though, were less clear . COCs that contained chlormadinone acetate or cyproterone acetate improved acne better than levonorgestrel although this apparent advantage was based on limited data . A COC with cyproterone acetate might result in better acne outcomes than one with desogrestrel; however, the three studies comparing these COCs produced conflicting results . Likewise, levonorgestrel showed a slight improvement over desogestrel in acne outcomes in one trial, but a second trial found no difference between the COCs . REVIEWERS' CONCLUSIONS: The three COCs evaluated in placebo-controlled trials are effective in reducing inflammatory and non-inflammatory facial acne lesions . Few differences were found in acne effectiveness between COC types . How COCs compare to alternative acne treatments is unknown since limited data were available regarding this question.

J Paediatr Child Health, 2004 Aug, 40(8), 483 - 6
Facial nerve paralysis secondary to acute otitis media in infants and children; Gaio E et al.; Nowadays, facial paralysis is an uncommon complication of acute inflammation of the middle ear, with an estimated incidence of 0.005%; it was not so rare in the pre-antibiotic era, occurring in 0.5-0.7% of middle ear inflammatory processes . We would like to highlight this complication of acute otitis media, a common paediatric complaint . We present three new cases of facial palsy in children with acute otitis media and discuss the etiological mechanisms and different approaches to the treatment; a flow chart for facial paralysis in acute otitis media is also presented . Our three patients recovered completely after mastoidectomy (first two cases) and myringotomy with antibiotic therapy (third case) . Facial paralysis is an uncommon complication of otitis media which requires appropriate care . Following our experience and revision of literature on the subject, antibiotic therapy and myringotomy are the first-line procedures . Surgery should be employed in case of acute or coalescent mastoiditis, suppurative complications and lack of clinical regression.

Curr Opin Mol Ther, 2004 Jun, 6(3), 344 - 9
Technology evaluation: rh lactoferrin, Agennix; Anderson J; Agennix is developing recombinant human (rh) lactoferrin, a glycoprotein with antibiotic, anti-inflammatory and immunomodulatory activity, for the potential treatment of cancers, asthma and chronic wounds . rh Lactoferrin is currently undergoing phase II clinical trials.

J Biomed Mater Res, 2004 Aug 15, 70B(2), 286 - 96
Bioresorbable nanofiber-based systems for wound healing and drug delivery: optimization of fabrication parameters; Katti DS et al.; Wound healing is a complex process that often requires treatment with antibiotics . This article reports the initial development of a biodegradable polymeric nanofiber-based antibiotic delivery system . The functions of such a system would be (a) to serve as a biodegradable gauze, and (b) to serve as an antibiotic delivery system . The polymer used in this study was poly(lactide-co-glycolide) (PLAGA), and nanofibers of PLAGA were fabricated with the use of the electrospinning process . The objective of this study was to determine the effect of fabrication parameters: orifice diameter (needle gauge), polymer solution concentration, and voltage per unit length, on the morphology and diameter of electrospun nanofibers . The needle gauges studied were 16 (1.19 mm), 18 (0.84 mm), and 20 (0.58 mm), and the range of polymer solution concentration studied was from 0.10 g/mL to 0.30 g/mL . The effect of voltage was determined by varying the voltage per unit electrospinning distance, and the range studied was from 0.375 kV/cm to 1.5 kV/cm . In addition, the mass per unit area of the electrospun nanofibers as a function of time was determined and the feasibility of antibiotic (cefazolin) loading into the nanofibers was also studied . The results indicate that the diameter of nanofibers decreased with an increase in needle gauge (decrease in orifice diameter), and increased with an increase in the concentration of the polymer solution . The voltage study demonstrated that the average diameter of the nanofibers decreased with an increase in voltage . However, the effect of voltage on fiber diameter was less pronounced as compared to polymer solution concentration . The results of the areal density study indicated that the mass per unit area of the electrospun nanofibers increased linearly with time . Feasibility of drug incorporation into the nanofibers was demonstrated with the use of cefazolin, a broad-spectrum antibiotic . Overall, these studies demonstrated that PLAGA nanofibers can be tailored to desired diameters through modifications in processing parameters, and that antibiotics such as cefazolin can be incorporated into these nanofibers . Therefore, PLAGA nanofibers show potential as antibiotic delivery systems for the treatment of wounds .

J Biomed Mater Res, 2004 Aug 15, 70B(2), 240 - 9
Development of hydroxyapatite bone scaffold for controlled drug release via poly(epsilon-caprolactone) and hydroxyapatite hybrid coatings; Kim HW et al.; A scaffold-coating design, the hydroxyapatite (HA) porous bone scaffold coated with poly(epsilon-)caprolactone (PCL) and HA powder hybrids, was developed for use as tissue-regeneration and controlled-release system . An antibiotic drug, tetracycline hydrochloride (TCH), was encapsulated within the hybrid coating layer through a dip-coating and solvent-casting method . Coating cycle and drug loading amount differed to control the level of drug-release rate . The HA scaffold framework, obtained by a polymeric foam reticulate method, exhibited a highly porous structure, with porosity and pore size of approximately 87% and 180 microm, respectively . The hybrid layer, consisting of PCL sheet and HA fine powders, was uniformly coated on the scaffold surface . The coating layer exhibited only PCL and HA phases and structures, revealing no chemical interaction among the coating components, as observed by X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) analyses . The coated-HA scaffolds showed an effective stress distribution behavior in response to an applied load, as confirmed by the compressive stress-strain curve . The mechanical properties of the coated scaffolds were improved highly with coatings; the compressive strength and elastic modulus of the cyclic coated scaffolds were approximately 3-4 times, and the energy absorption were approximately 8 times, higher than those without coating . These improvements were attributed mainly to the shielding of framework flaws by a flexible coating layer and partially to the thicker stems (porosity reduction) . The dissolution of the coated scaffolds in a phosphate-buffered saline (PBS) solution increased with incubation time . The drug was released sharply within the initial several hours ( approximately 2 h), but the rate decreased further, showing a sustained release . The release amount was well controlled via coating-cycle and initial drug loading amount, suggesting the effectiveness of the coating-scaffold design as a drug-delivery system .

Am J Kidney Dis, 2004 Aug, 44(2), e25 - 27
Telithromycin-induced acute interstitial nephritis: a first case report; Tintillier M et al.; Telithromycin, a ketolide antibiotic used for the treatment of community-acquired respiratory infections, is widely prescribed in primary care practice . Treatment-related adverse events are mainly of gastrointestinal origin and generally mild in intensity . The authors report the first case of telithromycin-induced severe acute interstitial nephritis . Practitioners should be aware of the possibility that telithromycin therapy could result in this form of drug-induced acute renal failure.

Biochemistry, 2004 Jul 27, 43(29), 9512 - 8
Structure-based design of Tet repressor to optimize a new inducer specificity; Henssler EM et al.; We constructed a mutant of the tetracycline-inducible repressor protein TetR with specificity for the tc analogue 4-de(dimethylamino)anhydrotetracycline (4-ddma-atc), which is neither an antibiotic nor an inducer for the wild-type protein . The previously published relaxed specificity mutant TetR H64K S135L displays reduced induction by tc but full induction by doxycycline (dox), anhydrotetracycline (atc), and 4-de(dimethylamino)-6-demethyl-6-deoxytetracycline (cmt3) . To create induction specificity for tc derivatives lacking the 4-dimethylamino grouping such as cmt3 and 4-ddma-atc, the residues at positions 82 and 138, which are located close to that moiety in the crystal structure of the TetR-{tc-Mg}(+)(2) complex, were randomized . We anticipated that a residue with increased size may lead to sterical hindrance, and screening for 4-ddma-atc-specific induction indeed revealed the mutant TetR H64K S135L S138I . Out of 24 exchanges only the addition of S138I to TetR H64K S135L yielded a mutant with a pronounced reduction of affinity for atc and dox, while the one for 4-ddma-atc is not affected . The ratio of binding constants revealed a 200-fold specificity increase for 4-ddma-atc over atc . The contributions of each single mutant to specificity indicate that the tc variants bind slightly different positions in the TetR tc binding pocket.

Rev Mal Respir, 2004 Feb, 21(1), 147 - 51
{Pulmonary nocardiosis and broncho-oesophageal fistula in a patient infected with HIV}; Luketombunga JC et al.; INTRODUCTION: We report a case of extensive pulmonary nocardiosis in a patient infected with HIV . CASE REPORT: It presented as bilateral cavitated masses and bulky necrotic mediastinal lymphadenopathy causing broncho-oesophageal fistulae . There was associated infection with Mycobacterium Avium . There was satisfactory progress following bipolar oesophageal isolation, nutrition via a jejunostomy and antibiotic therapy with co-amoxiclav . Healing of the fistulae after 11 months allowed surgical restoration of oesophago-gastric continuity . CONCLUSION: As with other bacteria, HIV can modify the clinical spectrum of nocardiosis.

Antivir Ther, 2004 Jun, 9(3), 441 - 5
Destabilization of the non-pathogenic, cellular prion-protein by a small molecular drug; Ochel HJ et al.; The presence of the normal cellular prion-protein (PrPc) is a prerequisite for the development of fatal, neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs) . We discovered a new biological activity of the well-known coumarin antibiotic novobiocin; the treatment of eukaryotic cells with novobiocin induces the rapid depletion of PrPc . This activity is shared by coumermycin A1, another coumarin with a related molecular structure . Novobiocin's effects on the prion-protein are time- and dose-dependent . No permanent damage to the treated cells was observed, which continue to proliferate after cessation of drug exposure . Most of the cellular proteins are unaffected by novobiocin treatment . Pretreatment with geldanamycin, an inhibitor of the aminoterminal ATPase of heat-shock protein 90 (Hsp90) partially antagonizes novobiocin's depletory activity . Concurrent treatment with the protease inhibitor chymostatin completely prevents PrPc loss . Here we show that the stability of the normal cellular prion-protein may be targeted pharmacologically . These findings open up a hitherto unknown avenue to the study of TSEs in general and may have therapeutic implications.

An Otorrinolaringol Ibero Am, 2004, 31(3), 231 - 6
{Cervical abscess after hemithyroidectomy . An unusual complication}; Pino Rivero V et al.; Cervical abscesses secondary to hemithyroidectomy are an uncommon complication . We report the clinical case of a 37 years-old male, diagnosed and operated for nodular goiter, who suffered a paratracheal purulent collection three weeks later . He was reoperated by drainage of the neck abscess and antibiotic hospitalary treatment during 8 days . In a control CT showed an improvement despite the presence of a seroma on the surgical wound . Cervical exploration was normal two weeks later . Thyroid surgery is catalogued as clean and does requires antibiotic therapy . This must only be kept for cases of surgical wound infection or local abscess and both of them are rare in the literature.

Am J Health Syst Pharm, 2004 Jun 15, 61(12), 1264 - 70
Clinical and economic benefits of a meropenem dosage strategy based on pharmacodynamic concepts; Kotapati S et al.; PURPOSE: The clinical and economic outcomes of a meropenem dosage strategy based on pharmacodynamic concepts are retrospectively reviewed . METHODS: The medical records of all patients receiving at least one day of meropenem at a large teaching hospital during 2002 were reviewed . Patients were included if they were clinically evaluable, had no prior successful antibiotic therapy, and received a meropenem dosage appropriate for renal function . Clinical outcomes were evaluated by the rate of response (days to normalization of temperature or lymphocyte count) and success rate . A cost-minimization analysis was performed from the hospital's perspective for level 1, 2, and 3 costs . The average wholesale price of meropenem for 2002 and the cost for one hospital day at our institution were used to calculate economic outcomes . RESULTS: Of the 136 patients identified as receiving at least one dose of meropenem, 85 met inclusion criteria, of whom 45 received meropenem 500 mg every six hours and 40 received meropenem 1000 mg every eight hours . No significant differences in demographics, site of infection, meropenem-related length of stay, or rate of response were found . Clinical success rates were similar between groups (p = 0.862) . Patients taking the 500-mg regimen received less meropenem during treatment than those in the 1000-mg group (13 g versus 18 g, respectively) (p = 0.012) . Median level 1 and 2 costs were significantly lower for the 500-mg regimen (p = 0.009 and p = 0.008, respectively) . Level 3 costs were not significantly different . CONCLUSION: A pharmacodynamically designed meropenem dosage strategy of 500 mg every six hours yielded similar clinical outcomes to a regimen of 1000 mg every eight hours and reduced the daily drug acquisition costs associated with antibiotic therapy.

Surg Laparosc Endosc Percutan Tech, 2004 Feb, 14(1), 5 - 8
Long-term complications of laparoscopic ventral and incisional hernia repair; Tagaya N et al.; To date, there have been no long-term follow-up studies of the results of laparoscopic ventral and incisional hernia repair . We evaluated the long-term complications of these repairs over a mean follow-up period of 64 months . Between March 1993 and April 2000, we retrospectively evaluated 9 patients who underwent ventral or incisional hernia repair with prosthetic material and one patient who received laparoscopic primary closure of a hernia defect . The prosthetic material polypropylene was used in one patient and an expanded-polytetrafluoroethylene patch was used in the other 8 . In one patient, the hernia was closed directly . In 7 patients, the prosthesis was fixed by stapling or tacking with no transfacial suture fixation and a 2-cm prosthesis overlap . In 2 later patients, we modified our technique by fixing the prosthesis by stapling or tacking with transfacial suture fixation and using prosthesis overlap of more than 3 cm . There were 2 episodes of hernia recurrence (20%), one of which required reoperation . Both occurred in patients in whom we used the unmodified repair technique . One of the patients in whom we used the unmodified technique developed a seroma which resolved spontaneously without antibiotic therapy . One patient in whom we used the modified technique developed infection (10%) requiring removal of the prosthetic material . The 2 episodes of hernia recurrence occurred 40 months after laparoscopic treatment, and the case of infection occurred 11 months after treatment . There were no episodes of recurrence in patients who received the unmodified surgery and had hernia defects less than 42 cm2 . To perform safe and effective laparoscopic repair of ventral or incisional hernias, it is necessary to use a prosthetic overlap of more than 3 cm from the edge of the hernia gate and to use transfacial suture fixation with nonabsorbable sutures . In addition, patients who undergo laparoscopic ventral or incisional hernia repair should be observed for more than 5 years.

BMC Cardiovasc Disord . 2004 Jul 16;4(1):10.
Resting tachycardia, a warning sign in anorexia nervosa: case report; Krantz MJ et al.; BACKGROUND: Among psychiatric disorders, anorexia nervosa has the highest mortality rate . During an exacerbation of this illness, patients frequently present with nonspecific symptoms . Upon hospitalization, anorexia nervosa patients are often markedly bradycardic, which may be an adaptive response to progressive weight loss and negative energy balance . When anorexia nervosa patients manifest tachycardia, even heart rates in the 80-90 bpm range, a supervening acute illness should be suspected . CASE PRESENTATION: A 52-year old woman with longstanding anorexia nervosa was hospitalized due to progressive leg pain, weakness, and fatigue accompanied by marked weight loss . On physical examination she was cachectic but in no apparent distress . She had fine lanugo-type hair over her face and arms with an erythematous rash noted on her palms and left lower extremity . Her blood pressure was 96/50 mm Hg and resting heart rate was 106 bpm though she appeared euvolemic . Laboratory tests revealed anemia, mild leukocytosis, and hypoalbuminemia . She was initially treated with enteral feedings for an exacerbation of anorexia nervosa, but increasing leukocytosis without fever and worsening left leg pain prompted the diagnosis of an indolent left lower extremity cellulitis . With antibiotic therapy her heart rate decreased to 45 bpm despite minimal restoration of body weight . CONCLUSIONS: Bradycardia is a characteristic feature of anorexia nervosa particularly with significant weight loss . When anorexia nervosa patients present with nonspecific symptoms, resting tachycardia should prompt a search for potentially life-threatening conditions.

Hum Pathol, 2004 Jul, 35(7), 897 - 9
Intestinal pseudotumorous gouty nodulosis: a colonic tophus without manifestation of gouty arthritis; Wu H et al.; A 37-year-old black woman with nephritis secondary to systemic lupus erythematosus, steroid-induced diabetes mellitus, and hypertension presented with fever, nausea, vomiting, and right upper quadrant abdominal pain with distension . Abdominal computed tomography (CT) scan revealed a colonic mass, and CT- guided fine-needle aspiration demonstrated birefringent crystalline material . After several weeks of antibiotic therapy, the patient underwent laparoscopic examination followed by extended right hemicolectomy for a large mass in the subserosa of the transverse colon . Pathological examination of this mass revealed it to be a gouty tophus . To our knowledge, no case of tophaceous gout presenting as an intestinal mass has previously been reported.

Cell Tissue Bank, 2003, 4(1), 37 - 41
Composite grafts in the treatment of osteosarcoma of the proximal humerus; Dudkiewicz I et al.; Treatment of osteosarcoma (OSA) of the proximal humerus poses many difficulties and challenges to the treating team . Between 1993 and 2000, we treated 11 patients (three women, eight men; age range, 17-74 years) suffering from OSA of the proximal humerus by 'composite': massive allografts and long humeral prosthesis . At presentation, 10 patients were at stage 2-B and one at stage 3-B of OSA . One patient presented with a pathologic fracture . All patients except patient No . 6, received preoperative chemotherapy followed by limb salvage surgery and postoperative chemotherapy.Surgical margins were graded as wide in all patients . Postoperative complications included non-union at the allograft/host junction (which united after auto grafting) and superficial wound infections that resolved after antibiotic therapy . All surgical procedures were performed by a team headed by an orthopedic oncologist and shoulder surgeon . At latest follow-up (December 2001) all patients, with the exception of one (who was at stage 3-B at presentation) were alive, and had good function of the upper limb . It is our opinion that the team approach comprising an orthopedic oncologist and shoulder surgeon greatly contributed to the good surgical outcome, and hence the good survival and functional results of the patients . Bone allograft offers a modular malleable durable solution to the resected bone segment.

Gene, 2004 Jun 9, 334, 53 - 61
Phosphorylation of AfsR by multiple serine/threonine kinases in Streptomyces coelicolor A3(2); Sawai R et al.; AfsK, a protein serine/threonine kinase, autophosphorylates on serine and threonine residues and phosphorylates serine and threonine residues of AfsR, a transcriptional activator for afsS involved in secondary metabolism in Streptomyces coelicolor A3(2) . pkaG encoding a 592-amino-acid protein and SCD10.09 (named afsL) encoding a 580-amino-acid protein, both of which encode an AfsK-like protein, were transcribed throughout growth . PkaG with a histidine-tag and the kinase catalytic domain of PkaG, produced in Escherichia coli, autophosphorylated dominantly on threonine and slightly on serine residues . In addition, these proteins phosphorylated AfsR on threonine and serine residues . The catalytic domain of AfsL also autophosphorylated and phosphorylated AfsR, on threonine and serine residues in both cases . AfsR was thus found to be phosphorylated by multiple kinases . Disruption of the chromosomal pkaG gene resulted in slightly reduced production of the pigmented antibiotic actinorhodin . These findings, together with the presence of about 40 AfsK homologues and at least five AfsR homologues in S . coelicolor A3(2), suggest that the regulatory networks via eukaryotic-type protein phosphorylation are more diverse and versatile than we have expected.

Eye, 2005 Jan, 19(1), 23 - 8
Topical application of autologous serum for the treatment of late-onset aqueous oozing or point-leak through filtering bleb; Matsuo H et al.; PURPOSE: To evaluate the efficacy of topical autologous serum application to stop aqueous oozing or point-leak through filtering bleb after trabeculectomy . PATIENTS AND METHODS: A total of 21 consecutive eyes with oozing and 21 eyes with a point-leak through a functional bleb after trabeculectomy with 5-fluorouracil or mitomycin C were enrolled in this randomized, case-control study . In eyes randomly assigned to the serum group, an antibiotic and the autologous serum, which was sterilely diluted to 20% with physiological saline, were topically applied four times a day for up to 12 weeks . In eyes assigned to the control group, the antibiotic alone was applied according to the same protocol . Intraocular pressure (IOP) and the presence of oozing or a point-leak were tested before and every 2 weeks after starting the treatments . RESULTS: In the serum and control groups, oozing stopped in 62.5 and 0% of eyes, respectively (P=0.003), and point-leaks stopped in 27.3 and 18.2%, respectively (P>0.9) . IOP significantly increased from 10.0+/-3.2 (mean+/-standard deviation) to 11.8+/-3.3 mmHg in eyes in which oozing stopped (P=0.066), and from 11.4+/-2.7 to 15.4+/-2.3 mmHg in eyes in which a point-leak stopped (P=0.042) . CONCLUSIONS: Autologous serum application was significantly effective to stop aqueous oozing but not point-leaks . Stopping oozing or point-leaks was significantly associated with an increase in IOP.Eye (2005) 19, 23-28 . doi:10.1038/sj.eye.6701422 Published online 9 July 2004.

Ann Vasc Surg, 2004 Mar, 18(2), 223 - 7
Saphenous vein loop to femoral artery arteriovenous fistula: a practical alternative; Pierre-Paul D et al.; Secondary to central venous stenosis or thrombosis, alternate sites for permanent hemodialysis need to be explored . The authors' experience with the greater saphenous vein to common femoral artery loop arteriovenous fistula (GSV-CFA AVF) is presented . A retrospective review was performed of 4 women and 3 men with a mean age of 52.7 (range, 44-68) years . The mean number of prior access procedures was 3.85 (range, 1-5) . Duplex ultrasound showed the greater saphenous vein (GSV) to be at least 3 mm in diameter . Perioperatively, no acute occlusion or significant steal syndrome developed . Groin wound complications (57.1%) resolved with local wound care and selectively antibiotic administration . Six patients developed mild to moderate edema, which required knee-high compression stockings . The mean follow-up was 15 (range, 9-24) months . Mean primary patency was 7 months, primary assisted patency was 15 months, and secondary patency was 16 months . The fistula was functional for hemodialysis in 71.4% (5/7) . All patients developed stenoses within the GSV loop, with a mean of 3.0 balloon angioplasties per fistula . Three secondary surgical procedures were performed (two pseudoaneurysm repairs, one vein patch angioplasty) . The GSV did not increase significantly in diameter . Use of a GSV-CFA AVF for dialysis access has acceptable results for alternate-site hemodialysis access . Secondary procedures were common . Factors recognized to be important for success were an adequate-sized GSV preoperatively, positioning of the GSV loop, and patient body habitus.

Optom Vis Sci, 2004 Jul, 81(7), 499 - 504
Late-onset blebitis/endophthalmitis: incidence and outcomes with mitomycin C; Muckley ED et al.; PURPOSE: To assess the outcomes of patients who had late infections after undergoing filtering surgery with mitomycin C with respect to treatment, resultant vision, and maintenance of intraocular pressure . METHODS: A retrospective review of 233 eyes that underwent trabeculectomy with mitomycin C with or without coincident cataract extraction and intraocular lens insertion from August 1993 to June 1997 was undertaken . Records were examined for postoperative infection occurring at least 6 months after filtering surgery . Age, sex, date, and type of surgery were reviewed and entered into a computerized database . RESULTS: Bleb infections occurred in 6 of 233 (2.6%) eyes that underwent mitomycin C filtering surgery . Four of these developed endophthalmitis . The average postoperative time until infection was 24.7 months . Two patients had bleb leaks, one of which progressed to endophthalmitis . On resolution of infection, all blebs remained functional, and vision returned to preblebitis acuities in 67% . CONCLUSION: Aggressive topical antibiotic therapy with daily observation may be appropriate in selected cases of late-onset blebitis and endophthalmitis . Eyes may continue to have good visual outcomes and functioning filters without need for additional surgery or hospitalization . Early recognition and appropriate management of infections may play a role in these outcomes.

J Biol Chem, 2004 Sep 10, 279(37), 38379 - 85 Epub 2004 Jul 12.
The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR); Burk O et al.; Induction of cytochrome P450 3A (CYP3A) by xenobiotics may lead to clinically relevant drug interactions . In contrast with other CYP3A family members, studies on the inducibility of CYP3A5 indicate conflicting results . We report the induction of CYP3A5 mRNA in 13 of 16 hepatocyte preparations exposed to rifampin . Furthermore, induction of CYP3A5 mRNA was observed in intestinal biopsies in three of eight probands following exposure to the antibiotic . The highest absolute levels of CYP3A5 transcripts were found following rifampin treatment in hepatocytes and intestines from carriers of CYP3A5*1 alleles . Elucidation of the mechanism involved in CYP3A5 induction revealed that constitutively activated receptor (CAR) and pregnane X receptor (PXR) transactivated the CYP3A5 promoter (-688 to +49) and that the transactivation was dependent on an everted repeat separated by 6 bp (ER6-dependent) . Treatment with the prototypical PXR ligand rifampin led to a 2-fold induction of the CYP3A5 promoter activity . In agreement with these observations, PXR and CAR bound specifically to the ER6 motif . Hepatic expression of PXR correlated with that of CYP3A5 mRNA levels in a bank of liver samples . Taken together, studies here revealed the presence of a functional ER6 motif in the CYP3A5 promoter located -100 bp upstream from the transcription start site, suggesting that CYP3A5 is inducible by mechanisms similar to those involved in CYP3A4 induction . Enhanced expression of CYP3A5 caused by exposure to inducers may phenocopy the effects of the high expression allele CYP3A5*1 . In this manner, induction of CYP3A5 may contribute to the overall importance of this P450 in drug metabolism and drug interactions.

Trans R Soc Trop Med Hyg, 2004 Sep, 98(9), 529 - 34
Failure of chloramphenicol prophylaxis to reduce the frequency of abscess formation as a complication of envenoming by Bothrops snakes in Brazil: a double-blind randomized controlled trial; Jorge MT et al.; Bites by many species of venomous snake may result in local necrosis at, or extending from, the site of the bite . The use of prophylactic antibiotics to prevent infection as a complication of local necrotic envenoming is controversial . A double-blind randomized controlled trial was carried out to assess whether antibiotic therapy is effective in this situation . Two hundred and fifty-one patients, with proven envenoming by snakes of the genus Bothrops, admitted to two hospitals in Brazil, between 1990 and 1996, were randomized to receive either oral chloramphenicol (500mg every six hours for five days) or placebo . One hundred and twenty-two of these patients received chloramphenicol (group 1) and 129 were given placebo (group 2) . There were no significant differences between the groups at the time of admission . Necrosis developed in seven (5.7%) patients in group 1 and in five (3.9%) patients in group 2 ( {Formula: see text} ) while abscesses occurred in six patients (4.9%) in group 1 and in six (4.7%) patients in group 2 ( {Formula: see text} ) . In conclusion, the use of orally-administered chloramphenicol for victims of Bothrops snake bite with signs of local envenoming on admission, is not effective for the prevention of local infections.

Transplant Proc, 2004 Jun, 36(5), 1613 - 4
Effect of human somatotropin hormone on cultured rat islets; Gurol AO et al.; Because growth hormone (GH) improves the insulin secretion capacity of isolated human fetal islets in vitro, we sought to show that it positively influences isolated rat islets . Islets isolated from Wistar albino rats by a modified automated system were cultured in media containing 87% RPMI 1640, 10% FCS, 2% antibiotic-antimycotic, and 1% L-glutamine for 12 +/- 2 days . The cultured islets were divided into two groups: growth hormone negative (Group I) and growth hormone positive (Group II) . On the 5th day we observed a decrease in the islet cell counts in both groups (Group I 28% versus Group II 45%) . On the 10th day, the decrease continued in the GH-negative group (59%), while the count remained stable in the GH-positive group . The viability of rat islets was determined by fluorescein diacetate (FDA) plus propidium iodide (PI) staining . In comparison to the peripheral green, central orange-red staining pattern of Group I islets upon fluorescent microscopy, Group II showed more compact islets . Cultured islets seemed to be brighter than those without GH in the cultured islets . In conclusion, we observed that 2 weeks of incubation in the presence of GH acts positively on cultured rat islets for both their amount and their viability .

Adv Exp Med Biol, 2004, 549, 91 - 6
Controversies in neonatal infection; May ML et al.; Antibiotics are an important part of neonatal care, but we must be careful that a short-sighted approach to their use does not magnify the problems they are designed to prevent . Prevention of infections by good infection control practices and minimizing risk factors for sepsis is just as important as appropriate antibiotic use . Attempts to eradicate colonizing organisms of low virulence may result in their replacement by more problematic organisms, so over-vigorous use of antibiotics to try to prevent infections is not always wise.

Protein Expr Purif, 2004 Aug, 36(2), 232 - 43
Purification and characterization of Mycobacterium tuberculosis KatG, KatG(S315T), and Mycobacterium bovis KatG(R463L); Wengenack NL et al.; Isoniazid, a first-line antibiotic used for the treatment of tuberculosis, is a prodrug that requires activation by the Mycobacterium tuberculosis enzyme KatG . The KatG(S315T) mutation causes isoniazid resistance while the KatG(R463L) variation is thought to be a polymorphism . Much of the work to date focused on isoniazid activation by KatG has utilized recombinant enzyme overexpressed in Escherichia coli . In this work, native KatG and KatG(S315T) were purified from M . tuberculosis, and KatG(R463L) was purified from Mycobacterium bovis . The native molecular weight, enzymatic activity, optical, resonance Raman, and EPR spectra, K(D) for isoniazid binding, and isoniazid oxidation rates were measured and compared for each native enzyme . Further, the properties of the native enzymes were compared and contrasted with those reported for recombinant KatG, KatG(S315T), and KatG(R463L) in order to assess the ability of the recombinant enzymes to act as good models for the native enzymes.

Recenti Prog Med, 2004 Jun, 95(6), 314 - 5
{Amoxicillin in tonsillectomy: preliminary data on the evaluation of serum and tissue concentrations}; Averono G et al.; Amoxicillin was administered to 50 patients with chronic recurrent tonsillitis waiting for tonsillectomy . Group A (N=16) received 2.2 g of amoxicillin plus clavulanic acid with intravenous injection 10 minutes before tonsillectomy Group B (N=34) was treated with 3 doses of amoxicillin-clavulanic acid administered orally the day before surgery, plus one oral administration 2 hours before tonsillectomy . Antibiotic doses were established on patient's weight using maximum suggested . The measures were, estimated in serum and in tonsils using High Performance Liquid Chromatography, (HPLC) . The data show better efficacy of intravenous administration than oral administration.

J Urol, 2004 Aug, 172(2), 448 - 53
Adverse reactions of nitrofurantoin, trimethoprim and sulfamethoxazole in children; Karpman E et al.; PURPOSE: Many children with urological disease require long-term treatment with antibiotics . In many cases the choice of medical instead of surgical management hinges on the implied safety of certain drugs . Recently some groups have advocated subureteral injection procedures to avoid long-term antibiotics for low grade reflux . We present a concise and relevant review on the use and adverse reactions of nitrofurantoin, trimethoprim and sulfamethoxazole in children . MATERIALS AND METHODS: We reviewed the literature regarding the safety and toxicity of these drugs . Information regarding absorption, excretion and dosing was also gathered to explain better the mechanisms of toxicity . RESULTS: Adverse reactions in children reported in the literature related to nitrofurantoin are gastrointestinal disturbance (4.4/100 person-years at risk), cutaneous reactions (2% to 3%), pulmonary toxicity (9 patients), hepatoxicity (12 patients and 3 deaths), hematological toxicity (12 patients), neurotoxicity and an increased rate of sister chromatid exchanges . Adverse reactions in children related to trimethoprim/sulfamethoxazole are almost exclusively due to the sulfamethoxazole component, including cutaneous reactions (1.4 to 7.4 events per 100 person-years at risk), hematological toxicity (0% to 72% of patients) and hepatotoxicity (5 patients) . The majority of adverse reactions were found in children on full dose therapy and not prophylaxis . CONCLUSIONS: The use of nitrofurantoin, trimethoprim and sulfamethoxazole is safe in children for long-term prophylactic therapy . The antibiotic safety issue should not be misconstrued as an argument for surgical therapy, whether minimally invasive or not . Adverse reactions exist to these medicines but they are less common than seen in adults, presumably because of the lower dose used for therapy, and the lack of significant comorbidities and drug interactions in children . Serious side effects are extremely rare and most are reversible by discontinuing therapy . The extremely low potential for significant adverse reactions should be discussed with parents.

Spine, 2004 Jul 15, 29(14), E289 - 93
Antifungal penetration into normal rabbit nucleus pulposus; Conaughty JM et al.; STUDY DESIGN: A rabbit model was used to assess the penetration into the nucleus pulposus of 3 commonly used antifungal medications: amphotericin B, amphotericin B lipid complex, and fluconazole . OBJECTIVES: The purpose of this study was to quantitate the penetration of antifungal medications into the normal rabbit nucleus pulposus . SUMMARY OF BACKGROUND DATA: Fungal infections of the spine are rarely, if ever, treated with medical management alone . Although antibiotic penetration into the nucleus pulposus has been studied extensively, no previous studies have attempted to quantitate the penetration of antifungals into the nucleus pulposus . METHODS: Twenty-four rabbits were given 2 doses of 1 of the antifungal medications studied . One hour after completion of the second dose, the animal was killed and the thoracolumbar spine was excised en bloc . Specimens of nucleus pulposus and serum were obtained and sent to an outside laboratory for analysis . Gas chromatography was used to determine the fluconazole tissue levels, and a bioassay was used to measure amphotericin B tissue levels . RESULTS: Three animals in the amphotericin B group died either after the first or second dose of medication was administered . Although amphotericin B and amphotericin B lipid complex did not show adequate penetration into the nucleus pulposus in 12 out of 12 animals, fluconazole reached therapeutic tissue levels in 5 out of 7 animals . CONCLUSIONS: Fluconazole showed superior penetration into the nucleus pulposus in an uninfected rabbit model when compared to amphotericin B and amphotericin B lipid complex . These findings were found to be statistically significant (P = 0.021), and they suggest that fluconazole may be a better choice for empiric therapy of fungal spine infections while cultures and sensitivities are pending.

Proc Natl Acad Sci U S A, 2004 Jul 20, 101(29), 10505 - 10 Epub 2004 Jul 09.
Directed evolution of ligand dependence: small-molecule-activated protein splicing; Buskirk AR et al.; Artificial molecular switches that modulate protein activities in response to synthetic small molecules would serve as tools for exerting temporal and dose-dependent control over protein function . Self-splicing protein elements (inteins) are attractive starting points for the creation of such switches, because their insertion into a protein blocks the target protein's function until splicing occurs . Natural inteins, however, are not known to be regulated by small molecules . We evolved an intein-based molecular switch that transduces binding of a small molecule into the activation of an arbitrary protein of interest . Simple insertion of a natural ligand-binding domain into a minimal intein destroys splicing activity . To restore activity in a ligand-dependent manner, we linked protein splicing to cell survival or fluorescence in Saccharomyces cerevisiae . Iterated cycles of mutagenesis and selection yielded inteins with strong splicing activities that highly depend on 4-hydroxytamoxifen . Insertion of an evolved intein into four unrelated proteins in living cells revealed that ligand-dependent activation of protein function is general, fairly rapid, dose-dependent, and posttranslational . Our directed-evolution approach therefore evolved small-molecule dependence in a protein and also created a general tool for modulating the function of arbitrary proteins in living cells with a single cell-permeable, synthetic small molecule.

Plant Physiol Biochem, 2004 Jun, 42(6), 529 - 36
Yeast hygromycin sensitivity as a functional assay of cyclic nucleotide gated cation channels; Mercier RW et al.; Cyclic nucleotide gated cation channels (CNGCs) are a large (20 genes in Arabidopsis thaliana) family of plant ligand gated (i.e . cyclic nucleotides activate currents) ion channels, however, little is known about their functional properties . One reason for this is the recalcitrance of plant CNGC expression in heterologous systems amenable to patch clamp studies . Here, we show results demonstrating the efficacy of using growth of a K+ uptake-deficient yeast (trk1,2) as a functional assay of CNGCs as inwardly-conducting cell membrane cation (K+) transporters . Prior work demonstrated that trk1,2 is hypersensitive to the antibiotic hygromycin (hyg) and that expression of an inwardly conducting K+ transporter suppresses hyg hypersensitivity . We find that increasing {hyg} in solid YPD medium inhibits trk1,2 growth around a filter disk saturated with 3 M K+ . Northern analysis indicated that message is transcribed in trk1,2 transformed with the CNGC coding sequences . Confocal imaging of yeast expressing CNGC-fluorescent fusion proteins indicated channel targeting to the cell membrane . Trk1,2 expressing several plant CNGCs grown in the presence of hyg demonstrated (a) greater growth than trk1,2 transformed with empty plasmid, and (b) enhanced growth when cAMP was added to the medium . Alternatively, cAMP inhibited growth of yeast transformed with either the empty plasmid, or the plant K+ channel KAT1; this channel is not a CNGC . Growth of trk1,2 was dependent on filter disk {K+}; suggesting that complementation of hyg hypersensitivity due to presence of a functional plant CNGC was dependent on K+ movement into the cytosol . We conclude that plant CNGC functional characterization can be facilitated by this assay system.

Ann Pharm Fr, 2004 Jul, 62(4), 244 - 6
{Legionella and legionellosis: of water, bacteria and men}; Gaillot O; Legionella species are natural dwellers of stagnant waters . Inhalation of contaminated aerosols may result in pneumonia, with a noteworthy mortality rate (20%) . However, such infections are infrequent, when compared to the rate of human exposition to Legionella . Legionellosis apparently occurs in patients in which respiratory tract macrophages allow bacterial replication, especially that of Legionella pneumophila serogroup 1 . Following a silent incubation period, large amounts of bacteria are released, resulting in a strong inflammatory response responsible for the severity of symptoms . The outcome depends on quick establishment of antibiotic therapy and early diagnosis is therefore necessary . Nowadays, the risk of acquiring legionellosis raises passionate discussions, in which the presence of Legionella in man-made water systems is often assimilated with the disease itself . Significant efforts are being made to detect and monitor the amount of Legionella in potentially contaminant environments . However, the prevention of legionellosis also requires that research efforts for a better understanding of the virulence mechanisms of infective strains are carried out.

Infect Control Hosp Epidemiol, 2004 Jun, 25(6), 512 - 4
The value of bacterial culture during clean orthopedic surgery: a prospective study of 1,036 patients; Bernard L et al.; OBJECTIVE: To determine whether bacterial cultures of the wounds of patients undergoing clean orthopedic surgery would help predict infection . METHODS: During 1 year, 1,256 cultures were performed for 1,102 patients who underwent clean orthopedic surgery . Results were analyzed to evaluate their ability to predict postoperative infection . RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of the cultures were 38%, 92%, 7%, and 99%, respectively . CONCLUSIONS: Cultures performed during clean orthopedic surgery were not useful for predicting postoperative infection.

Infect Control Hosp Epidemiol, 2004 Jun, 25(6), 477 - 80
Risk factors for surgical-site infection following primary total knee arthroplasty; Minnema B et al.; OBJECTIVE: To identify risk factors associated with the development of surgical-site infection (SSI) following total knee arthroplasty (TKA) . DESIGN: A case-control study . SETTING: A 1,100-bed, university-affiliated, tertiary-care teaching hospital . METHODS: Case-patients with SSI occurring up to 1 year following primary TKA performed between January 1999 and December 2001 were identified prospectively by infection control practitioners using National Nosocomial Infections Surveillance (NNIS) System methods . Three control-patients were selected for each case-patient, matched by date of surgery . Stepwise logistic regression analysis was used to determine the relation of potential risk factors to the development of infection . RESULTS: Twenty-two patients with infections (6 superficial and 16 deep) were identified . Infection rates per year were 0.95%, 1.07%, and 1.19% in 1999, 2000, and 2001, respectively . Logistic regression analysis identified two variables independently associated with the development of infection: the use of closed suction drainage (odds ratio {OR}, 7.0; 95% confidence interval {CI95}, 2.1-25.0; P = .0015) and increased international normalized ratio (INR) (OR, 2.4; CI95, 1.1-5.7; P = .035) . Factors not statistically associated with the development of infection included age, NNIS System risk index score, presence of various comorbidities, surgeon, duration of procedure or tourniquet time, type of bone cement or prosthesis used, or receipt of blood product transfusions . CONCLUSIONS: The use of closed suction drainage and a high postoperative INR were associated with the development of SSI following TKA . Avoiding the use of surgical drains and careful monitoring of anticoagulant prophylaxis in patients undergoing TKA should reduce the risk of infection.

Cell Biol Toxicol, 2004 Mar, 20(2), 83 - 96
Genotoxicity of streptozotocin in normal and cancer cells and its modulation by free radical scavengers; Blasiak J et al.; Streptozotocin (STZ) is an antibiotic which can be used to induce diabetes in experimental animals in order to have an insight into pathogenesis of this disease . To use STZ as a diabetogenic substance, its molecular mode of action should be elucidated . Using the alkaline comet assay, we showed that STZ at concentrations in the range 0.01-100 micromol/L induced DNA damage in normal human lymphocytes and HeLa cancer cells in a dose-dependent manner . Lymphocytes were able to remove damage to their DNA within a 30-min repair incubation, whereas HeLa cells completed the repair in 60 min . Vitamins C and E at 10 and 50 micromol/L diminished the extent of DNA damage induced by 50 micromol/L STZ . Pretreatment of the lymphocytes with the nitrone spin trap, alpha-(4-pyridil-1-oxide)-N-tert-butylnitrone (POBN) or ebselen, which mimics glutathione peroxidase, or pyrrolidine dithiocarbamate (PDTC) reduced the extent of DNA damage evoked by STZ . The cells exposed to STZ and treated with endonuclease III (Endo III), formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (AlkA), the enzymes recognizing oxidized and alkylated bases, displayed greater extent of DNA damage than those not treated with these enzymes . These results suggest that free radicals may be involved in the formation of DNA lesions induced by streptozotocin . The drug can also alkylate DNA bases . This broad range of DNA damage induced by STZ indicates that the drug may seriously affect genomic stability in normal and pathological cells.

Cell Mol Life Sci, 2004 Jul, 61(14), 1816 - 25
Cytochrome c release and endoplasmic reticulum stress are involved in caspase-dependent apoptosis induced by G418; Jin QH et al.; G418 is used extensively in transfection experiments to select eukaryotic cells that have acquired neomycin resistance genes, but the mechanism is still elusive . To investigate this, we treated normal rat kidney cells with G418 for 3 days and found that the cells presented typical apoptotic features such as cell shrinkage, nuclear fragmentation, and caspase-3 activation . However, there was no low-molecular DNA ladder . The pan caspase inhibitor z-VAD-fmk completely inhibited this type of apoptosis, suggesting a caspase-dependent mechanism . Caspase cascades in apoptosis induced by G418 were initiated by at least two pathways: the release of cytochrome c from mitochondria, which was observed under confocal microscopy, and endoplasmic reticulum stress, demonstrated by the increase in Ca2+ concentration and the cleavage of m-calpain and procaspase-12 . Both pathways activated caspase-9 . Inhibition of caspase-9 activity by z-LEHD-fmk prevented most of the cells from apoptosis, and E-64d, an inhibitor of calpain accentuated this block . The cleavage of caspase-9 and caspase-12 was blocked only by simultaneous application of z-VAD-fmk and E-64d, but not by either alone . E-64d did not prevent the release of cytochrome c . These results indicated that these two pathways were independent of each other.

Mol Cell Proteomics, 2004 Sep, 3(9), 934 - 8 Epub 2004 Jul 07.
A facile method for high-throughput co-expression of protein pairs; Alexandrov A et al.; We developed a method to co-express protein pairs from collections of otherwise identical Escherichia coli plasmids expressing different ORFs by incorporating a 61-nucleotide sequence (LINK) into the plasmid to allow generation of tandem plasmids . Tandem plasmids are formed in a ligation-independent manner, propagate efficiently, and produce protein pairs in high quantities . This greatly facilitates co-expression for structural genomics projects that produce thousands of clones bearing identical origins and antibiotic markers.

Clin Cancer Res, 2004 Jul 1, 10(13), 4538 - 49
Antibody-targeted chemotherapy with the calicheamicin conjugate hu3S193-N-acetyl gamma calicheamicin dimethyl hydrazide targets Lewisy and eliminates Lewisy-positive human carcinoma cells and xenografts; Boghaert ER et al.; PURPOSE: Linking a cytotoxic anticancer drug to an antibody that recognizes a tumor-associated antigen can improve the therapeutic index of the drug . We asked whether a conjugate of the cytotoxic antibiotic N-acetyl gamma calicheamicin dimethyl hydrazide (CalichDMH) and an antibody recognizing Lewis(y) (Le(y)) antigen could eliminate carcinomas that express Le(y) . Because Le(y) is highly expressed on carcinomas of colon, breast, lung, ovary, and prostate, a CalichDMH conjugate targeting Le(y) could provide a treatment option for various cancers . EXPERIMENTAL DESIGN: The humanized anti-Le(y) antibody hu3S193 was conjugated to CalichDMH via the bifunctional AcBut linker . Selectivity and avidity of the conjugate (hu3S193-CalichDMH) for Le(y)-BSA or Le(y+) cells was tested by BIAcore or flow cytometry . Cytotoxicity of hu3S193-CalichDMH was compared with toxicity of a control conjugate on monolayers of Le(y+) and Le(y-) carcinoma cells . Inhibition of tumor growth by hu3S193-CalichDMH was assessed on three types of s.c . xenografts . RESULTS: Hu3S193-CalichDMH had similar selectivity as hu3S193 . The conjugate had lower affinity for Le(y)-BSA but not for Le(y+) cells . When tested on monolayers of human Le(y+) carcinoma cells, hu3S193-CalichDMH was more cytotoxic than a control conjugate . This difference in efficacy was not noted on Le(y-) cells . Efficacy of hu3S193-CalichDMH depended on the expression of Le(y) and on the sensitivity of the cells to CalichDMH . In vivo, hu3S193-CalichDMH inhibited growth of xenografted human gastric (N87), colon (LOVO), and prostate carcinomas (LNCaP) . When used against N87 xenografts, hu3S193-CalichDMH arrested tumor growth for at least 100 days . CONCLUSION: Hu3S193-CalichDMH can specifically eliminate Le(y+) tumors . These results support development of this conjugate for treatment of carcinomas.

Breast J, 2004 Jul-Aug, 10(4), 363 - 5
Mycobacterium fortuitum breast infection following nipple-piercing, mimicking carcinoma; Lewis CG et al.; We reviewed a rare breast infection occurring 4 months after nipple piercing . Clinical examination suggested carcinoma . Mycobacterium fortuitum was eventually isolated after surgical biopsy and debridement . Antibiotic therapy was initiated intravenously using two drugs and oral therapy was continued for 6 months . A contralateral mycobacterial lesion emerged and was excised along with a residual fibrotic nodule at the original biopsy site . When adequate sampling of a complex and suspicious breast mass is benign and initial bacterial cultures are sterile, mycobacterial infection should be considered, particularly when there is a history of previous nipple piercing procedures.

Emerg Med Australas, 2004 Apr, 16(2), 125 - 34
Management of septic shock in childhood; Sparrow A et al.; OBJECTIVE: The object of this review is to discuss the recognition and treatment of septic shock in children based on principles of resuscitation, antibiotic use and recent therapeutic advances . METHODS: A comprehensive literature search combining these METHODS: on-line searches of Ovid, PubMed, and Medline; hand searches of 25 international journals; a trawl of 26 textbooks; searches of reference lists of pertinent articles; and scans of abstracts of recent international meetings . Various national and international units were contacted with regard to current research therapeutic strategies, both published and unpublished . CONCLUSIONS: Septic shock remains a leading cause of morbidity and mortality in children . Early administration of empirical antibiotic therapy reduces mortality . The keystone of resuscitation is aggressive volume replacement . Adjunctive therapies to modulate the inflammatory response may further enhance outcome, but do not replace principles of resuscitation.

Crit Rev Food Sci Nutr, 2004, 44(3), 173 - 84
Determination of aminoglycosides and quinolones in food using tandem mass spectrometry: a review; Kotretsou SI; The widespread use of antibiotics in dairy cattle management may result in the presence of antibiotic residues in food . While rapid screening tests are commonly used to detect the presence of antibiotics in food, more accurate chromatographic-mass spectrometric methods combined with tandem mass spectrometry (MS/MS) are required to determine the identity and quantity of the antibiotic present . These methods (HPLC/MS/MS) may have the greatest potential for accomplishing direct multi-residue identifications in complex biological matrices, such as food . This study reviews recent applications of tandem mass spectrometry in the determination of antibiotic residues, such as aminoglycosides and quinolones in food.

Am J Otolaryngol, 2004 Jul-Aug, 25(4), 263 - 5
Coxiella burnetii: an unusual ENT pathogen; Pappas G et al.; Coxiella burnetii, the causative agent of Q fever, is a prevalent zoonotic disease manifestating usually as atypical pneumonia or hepatitis . We describe 2 cases of serologically proven infection by Coxiella burnetii whose primary manifestations arose from the upper respiratory tract and were initially referred to the ear, nose, and throat (ENT) department . This is the first related report in medical literature . A 20-year-old woman with fever, bilateral tonsillitis, lymphadenopathy, and mild aminotransferase elevation, and a 30-year old man with spiking fever and laryngitis are presented . Diagnosis in both cases was achieved through evolving serological response to Coxiella burnetii . The importance of including the pathogen in the differential diagnosis of ENT patients, in assorted epidemiological settings, and the significance of the proper antibiotic selection are further discussed.

Zentralbl Chir, 2004 Jun, 129(3), 220 - 4
{Mitigated erysipelas after implantation of foreign material}; Sauer J et al.; When an infection occurs in the incisional area following surgery where foreign materials (i . e . endoprostheses, metal plates or plastic meshes) are implanted, a revision may become necessary because an infection in the area of the implant and involvement of the implant itself cannot be ruled out . In the case of a mitigated erysipelas, cultures taken during the revision seldom show bacterial growth . The disease progresses because surgery does not solve the problem of a weakened immune system and lymph stasis; on the contrary, it usually deteriorates the situation . A high dose antibiotic regimen is recommended as therapy for the mitigated erysipelas instead of an operative revision orally given . levofloxacin has proven to be successful reducing the recurrence rate . The course of two patients with mitigated erysipelas is represented for example in form of case studies . The patients were underwent several surgical revisions . But we had not to explant the endoprostheses at all . Finally both patients were treated with levofloxacin without further relapses.

Int J Pediatr Otorhinolaryngol, 2004 Aug, 68(8), 1023 - 6
The effect of fusafungine on post-operative pain and wound healing after pediatric tonsillectomy; Akbas Y et al.; OBJECTIVE: To investigate the effect of fusafungine spray on pain and healing process after pediatric tonsillectomy . METHODS: Sixty children with ages between 4 and 14 years underwent tonsillectomy or adenotonsillectomy . The patients were randomly divided into three groups and each group consisted of 20 patients . Group 1 was treated with antibiotic (amoxicillin-clavulanic acid) plus analgesic (acetaminophen), group 2 was treated with fusafungine plus analgesic (acetaminophen) and group 3 was treated with only fusafungine . The average ages were 7.8 + 3.4, 6.6 + 2.9, and 8.2 + 3.7 for groups 1, 2, and 3, respectively . Clinical evaluations were made after the operation on the 1st (T1), 3rd (T3), 7th (T7), 10th (T10), and 14th days (T14) . RESULTS: There was no significant difference in post-operative pain between study groups on the post-operative 1st, 3rd, and 7th days (P > 0.05), a statistically significant difference was present between groups 1 and 3, and groups 1 and 2 on the post-operative 10th and 14th day (P = 0.018 and 0.037, respectively) . Pain was less in groups 2 and 3 than in group 1 on the 10th and 14th day . Also there was a significant difference in healing time of the tonsillary beds between groups 1 and 2, and groups 1 and 3 on the 10th and 14th post-operative day (P = 0.031 and 0.001, respectively) . Healing was better in groups 2 and 3 than in group 1 on the 10th and 14th day . CONCLUSION: Fusafungine administration after tonsillectomy was found to be beneficial on post-operative pain and wound healing of tonsillary beds in pediatric population.

J Surg Res, 2004 Aug, 120(2), 304 - 11
Function of cryopreserved pig aortas; Rendal E et al.; OBJECTIVES: This paper analyzes the influence of storage in the gas phase or liquid phase on grafts, together with the thawing method (15 degrees C/min or 100 degrees C/min) on the postthawing activity of pig cryopreserved arterial grafts (aortas) . MATERIALS AND METHODS: Obtainment of arterial grafts (aortas) was from pigs with an ischemic time not greater than 2 h . Each aorta was divided into five fragments and assigned randomly to one control group of fresh aorta and four groups of cryopreserved aortas: group 1: gas phase/slow thawing; group 2: gas phase/rapid thawing; group 3: liquid phase/slow thawing; and group 4: liquid phase/rapid thawing . After the incubation in antibiotic solution, the cryopreservation in RPMI medium +10% DMSO was carried out and the level of cooling used was a reduction of 1 degrees C/min . The contraction and relaxation responses of the fresh and frozen/thawed arteries were carried out in organ baths . RESULTS: After thawing, the sensitivity to various agonists and maximal responses to the endothelium-dependent and independent relaxant agents were decreased . The maximal responses to the tested vasoconstrictors (KCl and noradrenaline) were, respectively, 13% and 24% of the responses obtained in unfrozen aortas . The endothelium-independent relaxant responses to sodium nitroprusside (SNP) were reduced and important reductions of the endothelium-dependent relaxant responses to acetylcholine were produced . CONCLUSIONS: The cryopreservation of pig aortas under the conditions used in this study led to a decrease in the contractility of the pig aortas, as well as a decrease in the endothelium-independent relaxant responses . On the other hand, no apparent preservation of the endothelium-dependent relaxant responses was observed.

Ophthalmology, 2004 Jul, 111(7), 1352 - 5
Three-day application of topical ofloxacin reduces the contamination rate of microsurgical knives in cataract surgery: a prospective randomized study; De Kaspar HM et al.; PURPOSE: To determine the rate of contamination of microsurgical knives during cataract surgery and the benefit of a 3-day versus a 1-hour preoperative application of topical ofloxacin in reducing the contamination rate . DESIGN: Prospective, randomized controlled trial . PARTICIPANTS: Seventy-eight eyes of 75 patients were randomly assigned to control (39 eyes) or study groups (39 eyes) . METHODS: All patients from both groups received 0.3% topical ofloxacin 1 hour before surgery, 5% povidone-iodine (PVI) scrub of the periorbital area, and 2 drops of PVI onto the ocular surface preoperatively . The patients in the study group also received ofloxacin 4 times a day for 3 days before surgery . MAIN OUTCOME MEASURES: Microsurgical knives were placed in blood culture broth media immediately after the incision had been made . The number of positive cultures and types of bacteria isolated were determined . RESULTS: Ten of 39 knives (26%) in the control group were found to be positive for bacterial growth compared with only 2 of 39 (5%) in the study group (P = 0.028) . CONCLUSIONS: The initial paracentesis incision frequently results in contamination of the microsurgical knife and may serve as a mechanism for introducing bacteria from the ocular surface into the anterior chamber . The application of topical ofloxacin for 3 days before surgery significantly reduces the contamination rate of the microsurgical knives, compared with a preoperative application of ofloxacin given 1 hour before surgery.

Eur J Epidemiol, 2004, 19(5), 473 - 9
Molecular epidemiology of diarrhoeagenic Escherichia coli associated with sporadic cases and outbreaks of diarrhoea between 2000 and 2001 in India; Kahali S et al.; Diarrhoeal infection caused by Escherichia coli is common in India with occasional outbreaks . However, association of different pathotypes of diarrhoeagenic E . coli (DEC) with the disease and its phenotypic and genotypic characteristics are not fully demonstrated . In this study, E . coli strains from sporadic cases and outbreaks of diarrhoea during 2000-2001 were confirmed as DEC by polymerase chain reaction (PCR) targeting the specific virulence genes . DEC represented by enterotoxigenic E . coli (ETEC), enteropathogenic E . coli (EPEC) and enteroaggregative E . coli (EAggEC) were mostly belonged to O serogroups 25, 86a, 114 and 146 . The gene astA was frequently detected among ETEC and EAggEC than EPEC . After initial screening of 200 DEC strains with serology and antibiotic susceptibility test, 32 strains representing ETEC, EPEC, and EAggEC isolated from different areas of India were included in the pulsed-field gel electrophoresis (PFGE) analysis . Using the PFGE results, the hierarchical representation of different linkage levels between the DEC strains were determined by unweighed pair-group arithmetic mean (UPGAMA) method . Except for few strains, clonotyping by PFGE revealed no correlation between pathotypes and serogroups as well as the place of isolation of the DEC strains . The prevailing clonal diversity among the different categories of DEC strains suggests that the pathotypes of DEC belonged to diverse clones.

Pediatrics, 2004 Jul, 114(1), 177 - 81
A randomized clinical trial to assess the effects of tympanometry on the diagnosis and treatment of acute otitis media; Spiro DM et al.; OBJECTIVES: Acute otitis media (OM) is the most common indication for the use of antibiotics among children . Otoscopy alone is an imprecise method for the diagnosis of OM, which may lead to inappropriate antibiotic use . We sought to determine whether tympanometry, as an adjunct to otoscopy, would significantly change physician prescribing behavior and whether physicians overprescribe antibiotics for OM, using independently graded tympanometry results as a standard . METHODS: A randomized, clinical trial was conducted among children 6 to 35 months of age who presented to a pediatric emergency department with either fever or upper respiratory infection symptoms . Children were randomized into 2 groups, in which the attending physician evaluated tympanometry results (Tymp Aware) or the attending physician was blinded to the tympanometry findings (Tymp Unaware) . Tympanometry curves were graded independently by using a modified version of the Jerger scale . RESULTS: Of the 698 patients enrolled, tympanometry was performed successfully for 99.3% . Antibiotics were prescribed for OM for 27.9% of all patients . No statistically significant difference in antibiotic prescription rates for OM between the Tymp Aware group (28.8%) and the Tymp Unaware group (26.8%) was found . Of all patients for whom antibiotics were prescribed for OM, 14% had normal curves for both ears and 40% had some tympanographic movement bilaterally . CONCLUSIONS: Tympanometry did not seem to change diagnoses or prescribing behavior in the group of physicians studied . Antibiotics were commonly prescribed for presumed OM in the absence of effusions documented with tympanometry.

Histopathology, 2004 Jul, 45(1), 82 - 6
Microscopic colitis with granulomatous inflammation; Saurine TJ et al.; AIMS: To present four cases in which the clinical and endoscopic findings were consistent with microscopic colitis, but the inflammatory infiltrate included a conspicuous granulomatous reaction . Microscopic colitis is defined as a syndrome of chronic watery diarrhoea with a chronic inflammatory cell infiltrate in the colonic mucosa and without significant abnormalities at colonoscopy . It encompasses both collagenous and lymphocytic colitis . METHODS AND RESULTS: In all cases the clinical course and endoscopic findings were unlike Crohn's disease and no infectious agents were identified . In all cases the main symptom was frequent watery diarrhoea, all were female and there were no endoscopic findings apart from mild mucosal erythema . Histologically, an active chronic inflammatory infiltrate was accompanied by scattered non-necrotizing granulomas, often closely associated with crypt epithelium (cryptolytic or pericryptal granulomas) . In three of the patients the symptoms began after antibiotic use or had worsened with antibiotic use . Two of the patients were on allopurinol at the time of the onset of symptoms . In two of the patients symptoms have continued for more than 10 years . One patient died as a result of medical complications relating to severe diarrhoea and dehydration . CONCLUSIONS: Microscopic colitis rarely may be characterized by granulomatous inflammation . Such patients should not be regarded as having Crohn's disease.

J Gen Physiol, 2004 Jul, 124(1), 59 - 69
Gramicidin-perforated patch recording revealed the oscillatory nature of secretory Cl- movements in salivary acinar cells; Sugita M et al.; Elevations of cytoplasmic free calcium concentrations ({Ca(2+)}(i)) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells . This process is driven by the apical exit of Cl(-) through Ca(2+)-activated Cl(-) channels, while Cl(-) enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na(+)-K(+)-2Cl(-) cotransporter (NKCC) and/or parallel operations of Cl(-)-HCO(3)(-) and Na(+)-H(+) exchangers, located in the basolateral membrane . To characterize the contributions of those activities to net Cl(-) secretion, we analyzed carbachol (CCh)-activated Cl(-) currents in submandibular acinar cells using the "gramicidin-perforated patch recording configuration." Since the linear polypeptide antibiotic gramicidin creates monovalent cation-selective pores, CCh-activated Cl(-) currents in the gramicidin-perforated patch recording were carried by Cl(-) efflux via Cl(-) channels, dependent upon Cl(-) entry through Cl(-) transporters expressed in the acinar cells . CCh-evoked oscillatory Cl(-) currents were associated with oscillations of membrane potential . Bumetanide, a loop diuretic, decreased the CCh-activated Cl(-) currents and hyperpolarized the membrane potential . In contrast, neither methazolamide, a carbonic anhydrase inhibitor, nor elimination of external HCO(3)(-) had significant effects, suggesting that the cotransporter rather than parallel operations of Cl(-)-HCO(3)(-) and Na(+)-H(+) exchangers is the primary Cl(-) uptake pathway . Pharmacological manipulation of the activities of the Ca(2+)-activated Cl(-) channel and the NKCC revealed that the NKCC plays a substantial role in determining the amplitude of oscillatory Cl(-) currents, while adjusting to the rate imposed by the Ca(2+)-activated Cl(-) channel, in the gramicidin-perforated patch configuration . By concerting with and being controlled by the cation steps, the oscillatory form of secretory Cl(-) movements may effectively provide a driving force for fluid secretion in intact acinar cells.

Aliment Pharmacol Ther, 2004 Jul 1, 20(1), 99 - 107
Seven-day therapy for Helicobacter pylori in the United States; Vakil N et al.; BACKGROUND: The ideal duration of Helicobacter pylori treatment in the United States and whether eradication therapy is as successful in nonulcer dyspepsia as in peptic ulcer disease are controversial topics . AIM: This study compared the efficacy of 3-, 7- and 10-day triple therapies with rabeprazole to a 10-day omeprazole control triple therapy for the eradication of Helicobacter pylori in patients with and without peptic ulcer disease in the United States . METHODS: This was a multicentre, double-blind, randomized, parallel-group trial . A total of 803 patients with H . pylori infection (determined by {13C}urea breath test and rapid urease test or culture) received either rabeprazole 20 mg b.d., amoxicillin 1000 mg b.d., and clarithromycin 500 mg b.d . for 3, 7, or 10 days, or 10 days of omeprazole 20 mg b.d . with the same antibiotic regimen (control) . H . pylori status was assessed by {13C}urea breath test > or =6 weeks after completing treatment . RESULTS: In intent-to-treat patients, the eradication percentages achieved for the rabeprazole-based treatments were: 3-day, 27% (95% confidence interval: 21%-34%); 7-day, 77% (95% confidence interval: 71%-83%); and 10-day, 78% (95% confidence interval: 72%-84%) . The eradication percentage with the 10-day omeprazole-based treatment was 73% (95% confidence interval: 67%-79%) . There was no statistically significant difference between the 7-day rabeprazole-based regimen and the 10-day rabeprazole- and omeprazole-based regimens . CONCLUSIONS: Seven-day therapy with rabeprazole, clarithromycin, and amoxicillin is similar in efficacy to 10-day therapies and had similar efficacy in patients with and without ulcer disease.

Acta Clin Belg, 2004 Mar-Apr, 59(2), 90 - 6
Infectious complications of acute pancreatitis; De Waele J et al.; Disease severity in patients with acute pancreatitis varies from mild disease with minimal morbidity, to severe disease in which a whole spectrum of local and systemic complications may occur . Infectious complications frequently arise, and especially infection of pancreatic necrosis is an important risk factor for mortality . Several strategies have been devised to reduce this risk, and the use of prophylactic therapy, e.g . selective digestive decontamination, can be considered in patients with documented necrosis fo the pancreas . Pancreatic abscesses and infected pseudocysts arise later in the course of disease, and should be considered as separate entities, due to differences in therapy and outcome of these patients . When infection occurs, source control using either surgical or percutaneous drainage techniques, is essential to avoid systemic complications.

Vasa, 2004 May, 33(2), 97 - 101
{Conservative therapy adapted to findings of superficial chronic venous ulcers}; Billmann MK et al.; A successful treatment of venous ulcers represents a special clinical challenge . The following conservative wound management of a high-risk patient presents an alternative to primary surgical treatment . A patient of 79 years in reduced general state with multiple underlying concomitant diseases is hospitalized with superinfected, necrotic and painful ulcers . Due to the severe morbidity of the patient the regular therapy of the underlying venous insufficiency consisting of stripping of great saphenous vein and ligation of perforator veins, is contraindicated . After interdisciplinary discussion conservative therapy is carried on . The conservative therapy includes initial local debridement, moist wound-healing dressings, compression therapy, systemic antibiotic and analgesic therapy, completed by stabilization of patient's general state . In regular intervals a photographic documentation of the wound is carried out . The period of treatment and observation is 63 days . Due to conservative wound management a clear improvement of the wound condition and of the patient's general state is observed . The period needed for change of wound dressing can be reduced from 2 hours to 30 minutes . The painscore is reduced from 8/10 to 4/10 as well as the analgesic need . The photographic documentation shows a clear progress of healing within 9 weeks . Under antibiotic therapy and conservative wound management the increased inflammation parameters are declining . By choosing a conservative therapeutical regime adapted to clinical findings superinfected, chronic venous ulcers are turned into a stable condition.

Chemistry, 2004 Jul 5, 10(13), 3241 - 51
Total synthesis of (+)-blasticidin s; Ichikawa Y et al.; The first total synthesis of the peptidyl nucleoside antibiotic, blasticidin S (1), has been achieved by the coupling reaction of cytosinine (3) and blastidic acid (2) . A key step in the synthesis of cytosinine (3) is the sigmatropic rearrangement of allyl cyanate 24; this reaction provided efficient and stereoselective access to 2,3-dideoxy-4-amino-D-hex-2-enopyranose (26 a) . Further elaboration of 26 a gave methyl hex-2-enopyranouronate 29, and cytosine N-glycosylation of 31 using the Vorbruggen conditions for the silyl Hilbert-Johnson reaction furnished the differentially protected cytosinine (32) in 11 steps from 2-acetoxy-D-glucal (14) (4.0 % overall yield) . Synthesis of the Boc-protected blastidic acid 47 in nine steps starting from chiral carboxylic acid 35 (23 % overall yield) utilized Weinreb's protocol for the preparation of benzyl amide 38 and Fukuyama's protocol for the synthesis of the secondary amine 40 . Assembly of the protected cytosinine (32) and blastidic acid (47) by the BOP method in the presence of HOBt, and finally elaboration to 1 by deprotection of the fully protected 54 established the total synthesis of blasticidin S (1).

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