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Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2000 Sep, 17(3), 295 - 7
{An experimental study of human tracheal epithelial transfer of human neutrophil defensin gene}; Huang N et al.; This study was amied at the possibility of production of the human neutrophil defensin in human tracheal epithelial cells when transfected with it's gene by using liposome . The plasmid vector carrying the human neutrophil defensin HNP1 (human Neutrophil Peptide-1) gene was used to transfect the human tracheal epithelial cells cultured in serum-free complement medium by lipofection reagent . Antiserum of HNP1 was prepared and used for the immunocytochemistry staining to detect expression of HNP1 gene in human tracheal epithelial cells . The result showed that recombinant eukaryote expression plasmid-pBabe-Neo-HNP1 could be transducted into human tracheal epithelial cells by liposomal transfection method . Transducted cells showed strong positive staining for HNP by immunohistochemistry assay . It was suggested that HNP1 gene could be productively transduced into human tracheal epithelial cells and expressed by using liposome . Antibiotic peptide gene might be used for gene therapy of respiratory infections.

Presse Med, 2001 Mar 10, 30(9), 431 - 3
{Primary tuberculosis of the breast}; Daali M et al.; BACKGROUND: Despite generalized BCG vaccination, tuberculosis remains a public health issue in France . Breast localizations are exceptional and constitute a diagnostic and therapeutic challenge . CASE REPORT: A 34-year-old woman who was nursing her 3-month old infant underwent emergency surgery for a breast abscess that had been incised one month earlier and treated with non-specific antibiotic therapy without success . All necrotic tissue was removed . Pathology provided the diagnosis of tuberculosis . An anti-tuberculosis regimen (INH + rifampicin + PZA + ethambutol for two months followed by INH + rifampicin for 7 months) was instituted . The epidemiology search was negative and no extension was found . The clinical course was favorable at 6 months . DISCUSSION: Tuberculosis is rarely localized in the breast . The main differential diagnosis is breast cancer . Pathology examination is required for diagnosis . Anti-tuberculosis antibiotic therapy may be associated with surgery in case of extension.

Am J Med Qual, 2001 Mar-Apr, 16(2), 58 - 60
Commentary: applying hospital quality indicators to clinical practice; Fisher C et al.; Hospitals use various methods to establish performance benchmarks . This may include cooperative data shared between organizations to allow broad, general comparisons . These can, however, be misinterpreted as representing standards of patient care . In the authors' institution, a more complete examination was made of one of these quality indicators when it appeared quality indicator standards were in conflict with standards of patient care . The authors conclude that quality indicators are valuable when screening a hospital, just as we utilize screening tests to identify patients at potential risk . Neither should we apply broad quality indicators as standards of care without a full understanding of their strengths and weaknesses and the foundation on which they are built.

Surg Endosc . 2000 Sep;14(9):866 . Epub 2000 Jul 26.
Capnocytophaga pleural empyema following laparoscopic Nissen fundoplication . A rare complication, a rare pathogen; Hourmont K et al.; Empyema complicating laparoscopic fundoplication is exceedingly rare, as is Capnocytophaga infection in the immunocompetent host, with the exception of gingivitis . We report a 29-year-old healthy man who presented with Capnocytophaga empyema 10 days after uneventful elective, laparoscopic Nissen fundoplication for gastroesophageal reflux disease . The exact mechanism of this complication is not known, but hypotheses, including a mini-Boerrhave's syndrome, can be drawn based on knowledge of the operation, the involvement of Capnocytophaga sp., and a patient history that included severe gingivitis . Because of prompt operative evacuation of the empyema and expedient identification of Capnocytophaga in the empyema fluid, appropriate antibiotic therapy was initiated . The infection was adequately treated, and the patient recovered fully . To the best of our knowledge, this is the first report of such a complication.

Clin Infect Dis, 2001 Apr 15, 32(8), 1191 - 200 Epub 2001 Mar 26.
Prophylactic antifungal therapy in the intensive care unit; Rex JH et al.; Antifungal prophylaxis is regularly used during treatment of patients with some cancers, as subgroups with high rates of invasive fungal infections are readily identified; for these patients, prophylaxis has been shown to be of value . High-risk liver transplant recipients also benefit from antifungal prophylaxis . Although the idea of extending this concept to the prevention of candidal infections in the larger population of critically ill patients who are seen in the intensive care unit (ICU) and who do not have neutropenia is attractive, implementation of this strategy is difficult because of the widely varying characteristics of patients in the ICU . Two studies have shown the benefit of such prophylaxis, but the benefit was shown only in selected groups of patients who had an unusually high risk for invasive candidiasis . Although the concept is sound, broad-scale implementation of antifungal prophylaxis would be premature and costly, both financially and with regard to resistance and toxicity . Investigations are needed to define and prove the utility of predictive tools for the identification of patients in the ICU who would benefit from prophylaxis.

Neurochirurgie, 2001 Feb, 47(1), 66 - 8
{Suboccipital tuberculosis: a case report}; Ibahioin K et al.; Suboccipital tuberculosis is an uncommon localization of Pott's disease . The gravity results from the neurological and life threatening risk . We report a case of suboccipital tuberculosis in a 22-year woman who survived . She was given an anti-tuberculosis antibiotic regimen due to pulmonary and pericardal involvement . The patient interrupted her treatment after four months and was admitted six months later for torticolis and spastic tetraplegia without sphincter disorders . Standard x-rays and MRI of the head confirmed suboccipital Pott's disease . Transcranial evacuation was performed and the patient was again given anti-tuberculosis antibiotics . The clinical course was favorable with definitive recovery 45 days later . The patient continued the antibiotic regimen for nine months . An orthopedic supporting device was worn for nine months . The diagnosis of suboccipital tuberculosis can be confirmed on MRI . Appropriate treatment is a subject of debate between exclusive orthopedic or combined orthopedic and surgical treatment . Prognosis depends on the neurological deficit, early diagnosis and prompt treatment.

J Clin Microbiol, 2001 Apr, 39(4), 1227 - 30
Novel mycobacterium related to Mycobacterium triplex as a cause of cervical lymphadenitis; Hazra R et al.; The Mycobacterium avium complex (MAC) is an important cause of cervical lymphadenitis in children, and its incidence appears to be increasing in the United States and elsewhere . In areas where Mycobacterium tuberculosis is not prevalent, M . avium causes the vast majority of cases of mycobacterial lymphadenitis, although several other nontuberculous mycobacterial species have been reported as etiologic agents . This report describes the case of a child with cervical lymphadenitis caused by a nontuberculous mycobacterium that could not be identified using standard methods, including biochemical reactions and genetic probes . Direct 16S ribosomal DNA sequencing showed greater than 99% homology with Mycobacterium triplex, but sequence analysis of the 283-bp 16S-23S internal transcribed spacer (ITS) sequence showed only 95% identity, suggesting that it is a novel species or subspecies within a complex of organisms that includes M . triplex . Mycolic acid high-performance liquid chromatography analysis also identified this isolate as distinct from M . triplex, and differences in susceptibility to streptomycin and rifampin between this strain and M . triplex were also observed . These data support the value of further testing of clinical isolates that test negative with the MAC nucleic acid probes and suggest that standard methods used for the identification of mycobacteria may underestimate the complexity of the genus Mycobacterium . ITS sequence analysis may be useful in this setting because it is easy to perform and is able to distinguish closely related species and subspecies . This level of discrimination may have significant clinical ramifications, as closely related organisms may have different antibiotic susceptibility patterns.

Int J Pharm, 2001 Feb 19, 214(1-2), 3 - 7
Production and characterisation of mucoadhesive nanosuspensions for the formulation of bupravaquone; Jacobs C et al.; Bupravaquone is a new naphthoquinone antibiotic against Cryptosporidium parvum and other parasites . It has attracted interest for the treatment of C . parvum infections, because of the lack of a drug in the treatment of mostly AIDS patients . The bioavailability of bupravaquone is limited when given orally . To overcome the problem of the high elimination rate caused by diarrhoea, typical for C . parvum infections, bupravaquone was formulated as a mucoadhesive nanosuspension, i.e . combining the properties of mucoadhesive drug delivery systems, in this case hydro gels, with nanosuspensions . In this study different polymers/hydro gels were employed to create a prolonged retention time for the drug in the infected gastrointestinal tract (GIT) . The second step to improve the bioavailability of bupravaquone was the formulation as nanosuspension . Therefore various concentrations of bupravaquone with different surfactants were tested . The production of these nanosuspensions was carried out by high pressure homogenisation . In addition to the classical stepwise production, about a new one step production method is described.

Lifetime Data Anal, 2001 Mar, 7(1), 5 - 19
Comparing the survival of two groups with an intermediate clinical event; Nam CM et al.; Consider a subject entered on a clinical trial in which the major endpoint is a time metric such as death or time to reach a well defined event . During the observational period the subject may experience an intermediate clinical event . The intermediate clinical event may induce a change in the survival distribution . We consider models for the one and two sample problem . The model for the one sample problem enables one to test if the occurrence of the intermediate event changed the survival distribution . This models provides a way of carrying out non-randomized clinical trial to determine if a therapy has benefit . The two sample problem considers testing if the probability distributions, with and without an intermediate event, are the same . Statistical tests are derived using a semi-Markov or a time dependent mixture model . Simulation studies are carried out to compare these new procedures with the log rank, stratified log rank and landmark tests . The new tests appear to have uniformly greater power than these competitor tests . The methods are applied to a randomized clinical trial carried out by the Aids Clinical Trial Group (ACTG) which compared low versus high doses of zidovudine (AZT).

Am J Hematol, 2001 Apr, 66(4), 303 - 5
Acute adrenal failure associated with fluconazole after administration of high-dose cyclophosphamide; Shibata S et al.; A 63-year-old man received high-dose cyclophosphamide for peripheral blood stem-cell (PBSC) harvest . He received 200 mg fluconazole . On day 3, atrial fibrillation developed with blood pressure declining to 78 mmHg . The rapid adrenocorticotropin (ACTH) test showed blunted adrenal responses . He was suspected as having adrenal failure, and fluconazole was discontinued . The rapid ACTH test became normal on Day 14, and PBSCs were successfully harvested . To clarify the association between adrenal failure and fluconazole, we resumed 400 mg fluconazole on Day 16 and repeated the test on Day 21, which showed blunted adrenal responses . This case demonstrates that prophylactic use of fluconazole can cause adrenal insufficiency .

Cancer Res, 2001 Mar 1, 61(5), 1799 - 804
Geldanamycin and its analogue 17-allylamino-17-demethoxygeldanamycin lowers Bcr-Abl levels and induces apoptosis and differentiation of Bcr-Abl-positive human leukemic blasts; Nimmanapalli R et al.; HL-60/Bcr-Abl cells, with ectopic expression of p185 Bcr-Abl tyrosine kinase (TK), and K562 cells, with endogenous expression of p210 Bcr-Abl TK, display a high degree of resistance against antileukemic drug-induced apoptosis (G . Fang et al., Blood, 96: 2246-2256, 2000) . Present studies demonstrate that treatment with ansamycin antibiotic geldanamycin (GA), or its less toxic analogue 17-allylamino-17-demethoxygeldanamycin (17-AAG), induces cytosolic accumulation of cytochrome c and cleavage and activities of caspase-9 and caspase-3, triggering apoptosis of HL-60/Bcr-Abl and K562 cells . GA or 17-AAG down-regulated intracellular Bcr-Abl and c-Raf protein levels, as well as reduced Akt kinase activity . Similar to Raf-1, v-Src, and Her-2-neu, Bcr-Abl TK has chaperone association with heat shock protein 90 (Hsp90) . By binding and inhibiting Hsp90, GA or 17-AAG treatment shifted the binding of Bcr-Abl from Hsp90 to Hsp70 and induced the proteasomal degradation of Bcr-Abl, because cotreatment with proteasome inhibitor PSC341 reduced both GA (or 17-AAG)-mediated down-regulation of Bcr-Abl levels and inhibited apoptosis of HL-60/Bcr-Abl and K562 cells . These data establish the in vitro activity of GA and 17-AAG against Bcr-Abl-positive leukemic cells and support the in vivo investigation of 17-AAG against Bcr-Abl-positive leukemias.

J Biol Chem, 2001 May 4, 276(18), 15269 - 74 Epub 2001 Feb 13.
Rotation of a complex of the gamma subunit and c ring of Escherichia coli ATP synthase . The rotor and stator are interchangeable; Tanabe M et al.; ATP synthase (F0F1) transforms an electrochemical proton gradient into chemical energy (ATP) through the rotation of a subunit assembly . It has been suggested that a complex of the gamma subunit and c ring (c(10-14)) of F0F1 could rotate together during ATP hydrolysis and synthesis (Sambongi, Y., Iko, Y., Tanabe, M., Omote, H., Iwamoto-Kihara, A., Ueda, I., Yanagida, T., Wada, Y., and Futai, M . (1999) Science 286, 1722-1724) . We observed that the rotation of the c ring with the cI28T mutation (c subunit cIle-28 replaced by Thr) was less sensitive to venturicidin than that of the wild type, consistent with the antibiotic effect on the cI28T mutant and wild-type ATPase activities (Fillingame, R . H., Oldenburg, M., and Fraga, D . (1991) J . Biol . Chem . 266, 20934-20939) . Furthermore, we engineered F0F1 to see the alpha(3)beta(3) hexamer rotation; a biotin tag was introduced into the alpha or beta subunit, and a His tag was introduced into the c subunit . The engineered enzymes could be purified by metal affinity chromatography and density gradient centrifugation . They were immobilized on a glass surface through the c subunit, and an actin filament was connected to the alpha or beta subunit . The filament rotated upon the addition of ATP and generated essentially the same frictional torque as one connected to the c ring . These results indicate that the gammaepsilonc(10-14) complex is a mechanical unit of the enzyme and that it can be used as a rotor or a stator experimentally, depending on the subunit immobilized.

Vet Microbiol, 2001 May 3, 80(1), 9 - 22
Development of disabled, replication-defective gene transfer vectors from the Jembrana disease virus, a new infectious agent of cattle; Metharom P et al.; Jembrana disease virus (JDV) is a newly isolated and characterised bovine lentivirus . It causes an acute disease in Bali cattle (Bos javanicus), which can be readily transmitted to susceptible cattle with 17% mortality . There is as yet no treatment or preventive vaccine . We have developed a gene transfer vector system based on JDV that has three components . The first of the components is a bicistronic transfer vector plasmid that was constructed to contain cis-sequences from the JDV genome, including 5'- and 3'-long terminal repeats (LTRs), 0.4kb of truncated gag and 1.1kb of 3'-env, a multiple cloning site to accommodate the gene(s) of interest for transfer, and an internal ribosome entry site plus the neomycin phosphotransferase (Neo) gene cassette for antibiotic selection . The second element is a packaging plasmid that contains trans-sequences, including gag, pol, vif, tat and rev, but without the env and packaging signals . The third is a plasmid encoding the G glycoprotein of vesicular stomatitis virus (VSV-G) to supply the vector an envelope for pseudotyping . Cotransfection of 293T cells with these three plasmid components produced VSV-G pseudotyped, disabled, replication defective, bicistronic JDV vectors encoding the green fluorescent protein (EGFP) and the Neo resistance selection maker simultaneously with a titre range of (0.4-1.2)x10(6)CFU/ml . Transduction of several replicating primary and transformed cells from cattle, primate and human sources and importantly growth-arrested cells with the JDV vectors showed high efficiency of EGFP gene transfer at 35-75%, which was stable and the expression of EGFP was long term . Furthermore, these JDV vectors were designed to suit the inclusion and expression of genes corresponding to JDV specific proteins, such as gag or env, for the development of vaccines for Jembrana disease . This strategy should also be applicable to other bovine diseases as well . The design and construction of the JDV vector system should facilitate the study of the lentivirology and pathogenesis of the diseases associated with JDV or other bovine virus infections . To our knowledge, this is the first such vector system developed from a cattle virus.

Am Fam Physician, 2001 Mar 15, 63(6), 1131 - 5, 1137-41
Endometrial biopsy; Zuber TJ; Endometrial biopsy is an office procedure that serves as a helpful tool in diagnosing various uterine abnormalities . The technique is fairly easy to learn and may be performed without assistance . The biopsy is obtained through the use of an endometrial suction catheter that is inserted through the cervix into the uterine cavity . Twirling the catheter while moving it in and out of the uterine cavity enhances uptake of uterine tissue, which is aspirated into the catheter and removed . Endometrial biopsy is useful in the work-up of abnormal uterine bleeding, cancer screening, endometrial dating and infertility evaluation . Contraindications to the procedure include pregnancy, acute pelvic inflammatory disease, and acute cervical or vaginal infections . Postoperative infection is rare but may be further prevented through the use of prophylactic antibiotic therapy . Intraoperative and postoperative cramping are frequent side effects.

Am Fam Physician, 2001 Mar 15, 63(6), 1113 - 6
Acute and chronic paronychia; Rockwell PG; Paronychia is one of the most common infections of the hand . Clinically, paronychia presents as an acute or a chronic condition . It is a localized, superficial infection or abscess of the paronychial tissues of the hands or, less commonly, the feet . Any disruption of the seal between the proximal nail fold and the nail plate can cause acute infections of the eponychial space by providing a portal of entry for bacteria . Treatment options for acute paronychias include warm-water soaks, oral antibiotic therapy and surgical drainage . In cases of chronic paronychia, it is important that the patient avoid possible irritants . Treatment options include the use of topical antifungal agents and steroids, and surgical intervention . Patients with chronic paronychias that are unresponsive to therapy should be checked for unusual causes, such as malignancy.

Periodontol 2000, 2000 Jun, 23, 63 - 72
Periodontal management of the patient with diabetes mellitus; Rees TD; Diabetes mellitus is a common medical disorder that will be encountered by every practicing dentist . Knowledge by the dentist of the general and oral signs and symptoms of undiagnosed or poorly controlled diabetes mellitus are essential, and patients displaying these signs or symptoms should receive medical referral . Patients suspected, or known to suffer from undiagnosed or uncontrolled diabetes mellitus should receive only emergency care until their health status has been properly evaluated . In the event the degree of control of a known diabetic is unknown or the patient is poorly controlled, antibiotic therapy should be administered in conjunction with any necessary surgical procedure or in the presence of oral infection . The practitioner must be prepared to manage diabetic emergencies should they occur in the dental office, and hypoglycemic incidents are most likely . The developing therapies now available for medical management of diabetes mellitus suggest that this condition will be more effectively controlled in the future, but medical consultation is important to proper periodontal patient management . New evidence suggests that advanced periodontal disease may interfere with diabetes mellitus control and the physician should be made aware of the patient's periodontal status . Under most circumstances, the well-controlled diabetes mellitus patient can receive safe and effective periodontal therapy with some modification of office protocol, and there is little reason to anticipate that the controlled diabetes mellitus patient cannot look forward to a lifetime of periodontal health if proper and timely periodontal therapy is rendered and the patient maintains effective oral hygiene measures accompanied by appropriate supportive periodontal recall therapy.

Heart Surg Forum, 1999, 2(1), 38 - 40
Low flow veno-venous ECMO via subclavian dialysis catheter for severe respiratory failure; Calderon M et al.; BACKGROUND: We present the case of a 12-year-old female with severe postoperative bacterial pneumonia unresponsive to conventional treatment following a failed renal transplant . CASE REPORT: The patient was placed on low flow veno-venous extracorporeal membrane oxygenation (ECMO) as an adjuvant treatment to antibiotic therapy and maximal ventilatory support . Venous ECMO resulted in rapid improvement and the patient was successfully weaned after 48 hours of circulatory assistance . Two days later, the patient was extubated and safely discharged from the intensive care unit . Eighteen months later, she remains stable on peritoneal dialysis and is awaiting a new donor kidney . CONCLUSIONS: Low flow veno-venous ECMO represents a new therapeutic alternative for critically ill patients whose condition does not meet the conventional ECMO criteria . Further clinical experience is still needed.

J Laryngol Otol, 2001 Apr, 115(4), 319 - 20
Bilateral subcutaneous emphysema of the orbits following nose blowing; Mohan B et al.; Orbital emphysema without evidence of any significant trauma is a rare occurrence . A case is reported here of bilateral subcutaneous emphysema of the orbital, in the absence of facial skeleton trauma, in a healthy adult male following nose blowing . It assumes importance because of potential complications such as loss of vision due to pressure effects and infection . Lamina papyracea is the most common site of bony defect and point of air entry into the orbit . Spontaneous resolution in around two weeks is usual.

J Laryngol Otol, 2001 Apr, 115(4), 316 - 8
Recurrent temporal petrositis; Al-Ammar AY; The objective of this paper is to present and discuss the common features of temporal petrositis and the different approaches to its management . Petrositis used to be common before the antibiotic era . It can be associated with life-threatening complications . The management of this problem used to be by an aggressive surgical approach . However, recent reports are describing good results with more conservative medical treatment and minimal surgical intervention, with the reservation of more aggressive surgical interventions for chronic or refractory cases.

Bull Exp Biol Med, 2000 Dec, 130(12), 1196 - 201
Ultrastructure of nuclear compartment in cardiomyocytes during regenerative and plastic insufficiency of the myocardium; Nepomnyashchikh LM et al.; We studied ultrastructure of nuclear compartment in cardiomyocytes during regenerative and plastic insufficiency of the myocardium induced by anthracycline antibiotic daunomycin . A peculiarity of ultrastructural organization of cardiomyocyte nuclei under these conditions is almost complete disappearance of the heterochromatin lumps . The earliest changes in nucleoli under conditions of disturbed DNA-dependent RNA synthesis are segregation of the granular and fibrillar nucleolonema components . Deep alterations in the nucleoli manifested by fragmentation and annulation correlate with pronounced changes in cardiomyocytes ultrastructure, intensive lysis of the myofilaments, reduction of the organelles, and enhanced autophagocytosis.

J Clin Gastroenterol, 2001 Apr, 32(4), 365 - 7
Recurrent pneumonia from an ileobronchial fistula complicating Crohn's disease; Gumbo T et al.; We report the case of a patient with Crohn's disease and recurrent pneumonia for over 3 years before the discovery of an occult ileopulmonary fistula and review five other cases in the literature . Patients often present with chronic cough productive of feculent sputum, pleuritic chest pain, and signs of pulmonary consolidation that fail to respond completely to antibiotic therapy . Mixed enteric flora is cultured from sputum and bronchial washings in most cases . Bronchoscopy findings range from chronic bronchial inflammation to feculent material in the airways . Barium enema is often diagnostic . Surgery and Crohn's-specific therapy are key components of curative therapy.

Proteins, 2001 May 1, 43(2), 134 - 44
Adaptations of the helix-grip fold for ligand binding and catalysis in the START domain superfamily; Iyer LM et al.; With a protein structure comparison, an iterative database search with sequence profiles, and a multiple-alignment analysis, we show that two domains with the helix-grip fold, the star-related lipid-transfer (START) domain of the MLN64 protein and the birch allergen, are homologous . They define a large, previously underappreciated superfamily that we call the START superfamily . In addition to the classical START domains that are primarily involved in eukaryotic signaling mediated by lipid binding and the birch antigen family that consists of plant proteins implicated in stress/pathogen response, the START superfamily includes bacterial polyketide cyclases/aromatases (e.g., TcmN and WhiE VI) and two families of previously uncharacterized proteins . The identification of this domain provides a structural prediction of an important class of enzymes involved in polyketide antibiotic synthesis and allows the prediction of their active site . It is predicted that all START domains contain a similar ligand-binding pocket . Modifications of this pocket determine the ligand-binding specificity and may also be the basis for at least two distinct enzymatic activities, those of a cyclase/aromatase and an RNase . Thus, the START domain superfamily is a rare case of the adaptation of a protein fold with a conserved ligand-binding mode for both a broad variety of catalytic activities and noncatalytic regulatory functions . Proteins 2001;43:134-144 .

J Assoc Physicians India, 2000 Jul, 48(7), 736 - 8
Infective endocarditis as a cause of fever in hemodialysis patients; Anandh U et al.; Vascular access infections are common in maintenance hemodialysis patients especially with dual lumen cuffed catheter . Persistent infections may lead to valvular seeding and the development of infective endocarditis . Though antibiotic therapy may often suffice, many patients may require surgical correction which carries a high risk of mortality . However appropriate preoperative therapy may considerably reduce the risk of surgery in maintenance hemodialysis patients.

Pediatr Transplant, 2000 May, 4(2), 123 - 31
Administration of recombinant human granulocyte-macrophage colony-stimulating factor to children undergoing allogeneic marrow transplantation: a prospective, randomized, double-masked, placebo-controlled trial; Trigg ME et al.; Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to 40 pediatric patients undergoing partially matched related, or closely matched unrelated, allogeneic marrow transplants . This trial was set up in a prospective, randomized, double-masked, placebo-controlled manner to establish if the administration of GM-CSF to such patients enhanced neutrophil recovery in this allogeneic transplant setting . The GM-CSF group had a significantly shorter time to neutrophil recovery to > 500 x 10(9) cells/L (15 days) than the placebo group (p = 0.0036) . In addition, the GM-CSF group had a significantly shorter neutrophil recovery time to > 1,000 x 10(9) cells/L (18 days) than the placebo group (p = 0.0053) . The primary objective of this study was met by showing that GM-CSF enhanced neutrophil recovery in this allogeneic setting . However, within the study group of patients, there was no effect of GM-CSF on the incidence or severity of graft-vs.-host disease (GvHD), one of the secondary end-points of the study . With regard to the other secondary end-points, there was no effect of GM-CSF on marrow cellularity, duration of systemic antibiotics given for real infections or as prophylaxis to prevent infections, risk of significant infections (as defined by systemic culture of virus, fungus, or bacteria), and duration or cost of hospitalization, platelet recovery, and nutritional support . With the secondary end-points, it will be necessary to study larger numbers of pediatric patients to identify differences that are small in this study group . In conclusion, GM-CSF can be safely administered to children with few, if any, significant side-effects . Additional work remains to facilitate earlier discharge of patients and decreased antibiotic usage, to offset the cost of using a neutrophil growth factor.

J Pharm Biomed Anal, 2001 Feb, 24(4), 629 - 36
Simultaneous identification and quantitative determination of neomycin sulfate, polymixin B sulfate, zinc bacytracin and methyl and propyl hydroxybenzoates in ophthalmic ointment by TLC; Krzek J et al.; A thin layer chromatographic-densitometric method for identification and quantitation of neomycin sulfate, polymixin B sulfate, zinc bacytracin and auxiliary substances (methyl and propyl hydroxybenzoates) in ophthalmic ointment was developed . To separate these constituents the silica gel coated TLC plates and two mobile phases were used . The suitable mobile phases were: methanol-n-butanol-ammonia 25%-chloroform (14:4:9:12, v/v/v/v) for determination of antibiotics and n-pentane-glacial acetic acid (66:9, v/v) for methyl and propyl hydroxybenzoates . The antibiotic chromatograms were detected by using ninhydrin ethanol solution, while densitometric measurements were made at lambda = 550 nm . Hydroxybenzoates were identified by UV measurements at lambda = 260 nm . The constituents under consideration were well separated at sufficient detection level . The recovery for all constituents ranged from 98.08% to 104.95%.

Drugs, 2001, 61(2), 187 - 96
Prophylaxis against herpesvirus infections in transplant recipients; Ljungman P; Herpesvirus infections are important after stem cell and organ transplant . During the last decades several antiviral agents have been introduced with efficacy against herpesviruses . These agents are the nucleoside analogues aciclovir, valaciclovir, famciclovir, and ganciclovir; the nucleotide analogue cidofovir; and the pyrophosphate analogue foscarnet . Several studies have been performed with antiviral agents with the aim to reduce morbidity and mortality associated with herpesvirus infections in transplant recipients . Aciclovir and valaciclovir have been examined in randomised, controlled trials in both solid organ and stem cell transplant patients, and were shown to be very effective for the prevention of herpes simplex virus (HSV) and varicella-zoster virus infections . In addition, these drugs were shown to reduce cytomegalovirus (CMV) infection and improve survival in allogenic stem cell transplant patients and to reduce CMV infection, CMV disease (aciclovir and valaciclovir), and acute rejection (valaciclovir) in renal transplant patients . Ganciclovir is very effective for the prevention of CMV infection and disease in both stem cell and solid organ transplant recipients . It can also be used in preemptive strategies in which the aim is to prevent CMV disease in patients who have ongoing CMV infection documented by antigenaemia or detection of CMV DNA . The latter strategy has the advantage of reducing the exposure to the drug and thereby the risk for toxicity . Foscarnet has also been shown to be effective as preemptive therapy for CMV in allogenic stem cell transplant patients and as therapy for aciclovir-resistant HSV infections . Finally cidofovir is an interesting agent with broad spectrum antiherpesvirus efficacy . However, because of the drug's toxicity profile, further studies are needed.

Carbohydr Res, 2001 Feb 15, 330(3), 319 - 24
Practical synthesis of a tetrasaccharide derivative corresponding to ristomycin A and ristocetin A; Zhang M et al.; A practical synthesis of fully benzoylated tetrasaccharide, whose free form is indispensable to the antibiotic ristomycin A for the process of dimerization and binding to the cell wall, was achieved via sequential assembly of the building blocks, allyl 3,4-di-O-benzoyl-alpha-D-glucopyranoside, 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate, 2-O-acetyl-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate, and 2,3,5-tri-O-benzoyl-alpha-D-arabinofuranosyl trichloroacetimidate . A one-pot preparation of allyl 3,4-di-O-benzoyl-2-O-tert-butyldimethylsilyl-6-O-triphenylmethyl-alpha-D-glucopyranoside is described, and regioselective glycosylation is carried out using perbenzoylated sugar trichloroacetimidates as glycosyl donors in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf).

Acta Otorrinolaringol Esp, 2000 Nov-Dec, 51(8), 719 - 23
{Diagnostic-therapeutic approach to internal jugular thrombosis}; Morales-Salas M et al.; The internal jugular vein thrombosis is a rare and critical disease . The infection of the head and neck deep spaces it is not the main cause since the antibiotic era . The ENT neoplasms and iatrogenic etiology are more frequent . Anodyne symptoms and vital complications are important to obtain an early diagnose and therapy, to improve the prognosis . The objective of this review is to obtain a certainly therapeutic criteria in the approach to this entity.

Ann Acad Med Singapore, 2000 Nov, 29(6), 753 - 6
Otogenic lateral sinus thrombosis--a case report; See KC et al.; INTRODUCTION: We portray and discuss a case of lateral sinus thrombosis following acute otitis media and mastoiditis . CLINICAL PICTURE: The patient presented with otorrhoea, otalgia, neck pain, fever and chills . TREATMENT: Cortical mastoidectomy was performed . Intravenous antibiotics and heparin were administered . OUTCOME: The patient had a complete recovery with no sequelae . CONCLUSIONS: Neurotologic complications of suppurative otitis media like meningitis, cerebral abscess, extradural abscess and dural sinus thrombosis are rare in the antibiotic era . Hence, doctors today have to maintain extra vigilance and a high index of suspicion for such complications.

J Antibiot (Tokyo), 2001 Jan, 54(1), 84 - 90
Borrelidin inhibits a cyclin-dependent kinase (CDK), Cdc28/Cln2, of Saccharomyces cerevisiae; Tsuchiya E et al.; We identified borrrelidin, a member of macrolide antibiotic, as an inhibitor of a cyclin-dependent kinase of the budding yeast, Cdc28/Cln2 . A 50% inhibition concentration (IC50) of borrelidin for Cdc28/Cln2 was 24 microM . In addition, borrelidin arrests both haploid and diploid cells in G1 phase at the point indistinguishable from that of alpha-mating pheromone, at concentrations not affecting the gross protein synthesis . Although the inhibition of CDK activity may not be a solo cause of the G1 arrest, our results indicate that borrelidin is a potential lead compound for developing novel CDK inhibitors of higher eukaryotes.

Haematologica, 2000 Nov, 85(11 Suppl), 58 - 61
Artificial nutrition and bone marrow transplantation; Candusso M et al.; Parenteral nutrition has a central role in the supportive therapy of patients submitted to a BMT . A central catheter is mandatory for transfusions, antibiotic therapy and a proper nutrition . A good nutritional support contributes to maintain hydration, reduce lean body mass loss, increase patient comfort and improve survival in patients who can not eat or absorb for a prolonged period of time . After a BMT metabolic complications are frequent and require careful monitoring; in critical care patients, the major risks are electrolyte and glucose disturbances . Liver disease is a main metabolic complication of PN, but it can occur in any cancer patient due to therapy or to graft-versus-host disease . Its best prevention requires the avoidance of prolonged enteral fasting.

Bioorg Med Chem Lett, 2001 Mar 12, 11(5), 651 - 4
Anion recognition by thiostrepton; Godoy-Alcantar C et al.; A bicyclic polypeptide antibiotic thiostrepton forms both 1:1 and 1:2 complexes with anions (as tetrabutylammonium salts) in organic solvents with K2 >K1 for F- and K2<<K1 for all other anions studied . Relative stabilities of 1:1 complexes in DMSO are AcO- approximatelyF->>Cl-, Br-, HSO4-, H2PO4-, but in CHCl3 they follow a different order: Cl- approximatelyHSO4- >F- approximately AcO- > Br > H2PO4- . The binding mode of anions to thiostrepton is discussed on the basis of solvent effects on the complexation selectivity.

Mol Cells, 2001 Feb 28, 11(1), 41 - 7
Excision repair of adozelesin-N3 adenine adduct by 3-methyladenine-DNA glycosylases and UvrABC nuclease; Jin SG et al.; Adozelesin is a synthetic analog of the antitumor antibiotic CC-1065, which alkylates the N3 of adenine in the minor groove in a sequence-selective manner . Since the cytotoxic potency of a DNA alkylating agent can be modulated by DNA excision repair system, we investigated whether nucleotide excision repair (NER) and base excision repair (BER) enzymes are able to excise the bulky DNA adduct induced by adozelesin . The UvrABC nuclease and 3-methyladenine-DNA glycosylase, that exhibit a broad spectrum of substrate specificity, were selected as typical NER and BER enzymes, respectively . The adozelesin-DNA adduct was first formed in the radiolabeled restriction DNA fragment and its excision by purified repair enzymes was monitored on a DNA sequencing gel . The treatment of the DNA adduct with a purified UvrABC nuclease and sequencing gel analysis of cleaved DNA showed that UvrABC nuclease was able to incise the adozelesin adduct . The incision site corresponded to the general nuclease incision site . Excision of this adduct by 3-methyladenine-DNA glycosylases was determined following the treatment of the DNA adduct with a homogeneous recombinant bacterial, rat and human 3-methyladenine-DNA glycosylases . Abasic sites generated by DNA glycosyalses were cleaved by the associated lyase activity of the E . coli formamidopyrimidine-DNA glycosylase (Fpg) . Resolution of cleaved DNA on a sequencing gel showed that the DNA glycosylase from different sources could not release the N3-adenine adducts . A cytotoxicity assay using E . coli repair mutant strains showed that E . coli mutant strains defective in the uvrA gene were more sensitive to cell killing by adozelesin than E . coli mutant strain defective in the alkA gene or the wild type . These results suggest that the NER pathway seems to be the major excision repair system in protecting cells from the cytotoxicity of adozelesin.

Bioresour Technol, 2001 May, 78(1), 31 - 5
Chromate tolerant bacteria isolated from tannery effluent; Verma T et al.; The occurrence of metal tolerant and antibiotic resistant organisms was investigated in tannery effluent . Seventy-seven isolates comprising heterotrophs (41) and coliforms (36) which were tolerant to chromate level of > 50 microg/ml were selected for detailed study . The majority of the coliforms were resistant to higher levels of chromate (200 microg/ml) whereas around 3% of the heterotrophs were resistant to Cr6+ at a level of > 150 microg/ml . All chromate tolerant heterotrophs were also tolerant to Cu2+ (100%) whereas only 58.53% coliforms were tolerant to Cu2+ . Except in the case of Cd2+ a higher number of heterotrophs were found tolerant to other heavy metals tested . Both groups of isolates were found sensitive to mercury . Resistance to cephaloridine was more abundant (P < 0.001) in coliforms as compared to heterotrophs . On the other hand a significantly higher number (P < 0.01) of heterotrophs showed resistance to streptomycin and carbencillin . All coliforms were sensitive to chloramphenicol . Around 80%) and 31.70% of coliforms and heterotrophs exhibited a relationship to the combination of metals and antibiotics . Both heterotrophs and coliforms tolerant to Hg2+ were also resistant to polymixin-B.

J Immunother, 2001 Mar-Apr, 24(2), 188 - 92
A prospective, randomized, double-blind, placebo-controlled trial evaluating the effect of nystatin on the development of oral irritation in patients receiving high-dose intravenous interleukin-2; Ohnmacht GA et al.; Interleukin-2 (IL-2) has been used to treat patients with metastatic melanoma and renal cell cancer for nearly two decades, and much progress has been made in ameliorating its adverse effects . One bothersome adverse effect, oral pain or oral irritation, is usually treated with an oral antifungal antibiotic, nystatin . The authors performed a prospective, randomized, double-blind, placebo-controlled trial involving 64 patients to evaluate the effect of prophylactic administration of nystatin or placebo on the development of oral irritation in patients receiving high-dose intravenous IL-2 . No difference was found between patients randomized to receive nystatin or placebo in their rates of development of oral irritation, the severity of IL-2 adverse effects, the duration of their treatment, the rate of development of positive studies for oral yeast, or their pattern of experiencing other adverse effects . Thus, patients who receive high-dose intravenous IL-2 should not be treated prophylactically with nystatin to prevent oral irritation, and clinicians should seek evidence of the presence of oral thrush before using antifungal agents to treat oral pain in these patients.

Arch Mal Coeur Vaiss, 2001 Feb, 94(2), 157 - 61
{Subacute infectious endocarditis due to the agent of cat scratch fever: Bartonella henselae}; Grand A et al.; The diagnosis of severe mitral stenosis with left atrial thrombus was rectified at valvular replacement in a 48-year old immuno-competent man who was a cat owner . The mass in the left atrium was, in fact, a large endocarditic vegetation . Pre- and postoperative blood cultures were negative as was culture of the excised mitral valve . The diagnosis of infectious endocarditis (IE) due to Bartonella Henselae was made from a positive serological test (1600) and identification of the germ by genetic amplification . Antibiotic therapy was continued for 6 months and the patient was cured with a follow-up of 4 years . Bartonella Henselae IE is very rare (14 reported cases) and affects mainly the aortic valve, often giving rise to very large vegetations which, in half the cases, are complicated by systemic emboli . Germs like Batonella are sensitive to most antibiotics, especially the aminosides and macrolides . In Bartonella Henselae IE, valve replacement is the rule (13 out of 14 cases) and the prognosis is usually good . Sero-diagnosis of Bartonellosis should be part of the systematic investigation of all blood culture negative IE.

J Telemed Telecare, 2000, 6(6), 339 - 42
Remote access to an expert system for infectious diseases; Tountas Y et al.; An expert-system antibiotic information database was developed in order to help non-specialist doctors to choose the appropriate treatment for patients with infectious diseases . Fifty doctors conducted a pilot trial of the database, using modern access and the telephone network . During an eight-month study period, 1053 queries were received . The range of duration of the queries was 130-350 s . Of the queries, 473 (45%) were for particular patients with an infectious disease . The response rate to a questionnaire mailed out to the users at the end of the project was 100% . All doctors, even those who had limited experience with computers, found it easy to understand and to use the database.

Clin Transplant, 2001 Apr, 15(2), 142 - 5
The use of intravenous tacrolimus and mycophenolate mofetil as induction and maintenance immunosuppression in simultaneous pancreas--kidney recipients with previous transplants; Ciancio G et al.; Clinical trials using quadruple immunosuppression that include the combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas-kidney (SPK) transplantation . In attempting to obtain a low rejection rate without antibody induction therapy, we proceeded with the combination of TAC intravenous (i.v.), MMF, and steroids as induction therapy and as primary immunosuppression for recipients with previous transplants . In this study, we analyzed 10 patients who received previous transplants, treated with low-dose TAC i.v . as induction therapy . Group A consisted of 6 patients with previous transplants that underwent SPK and group B consisted of four recipients with previous SPK that underwent cadaveric kidney transplants . For group A, the previous transplants were: living related kidney (LRK) followed by islet cell (IC) transplant (n=2), LRK transplant (n=1), cadaver kidney (CAD) and IC transplant (n=1), SPK (n=1), and three previous CAD kidney transplants (n=1) . In group A, all six kidneys were lost due to recurrent diabetic nephropathy, IC possibly to rejection, and the pancreas due to thrombosis . In group B with previous SPK transplants, three recipients lost their kidney to chronic rejection and one to long-term use of a nephrotoxic antibiotic . Currently, in all group A and B patients, the kidney and the pancreas are functioning, although 1 patient in group A developed type 2 diabetes (normal fasting C-peptide) . Two patients in group A developed three rejection episodes that responded to steroid treatment . The results indicate the TAC i.v . in combination with oral TAC, MMF, and steroids offer effective induction therapy in patients with previous transplants.

Br J Ophthalmol, 2001 Apr, 85(4), 393 - 6
The epithelial flap for photorefractive keratectomy; Shah S et al.; BACKGROUND/AIMS: Epithelial debridement for photorefractive keratectomy (PRK) is associated with pain, slower visual recovery, and may be aetiological in haze production . The aim of this study was to assess the clinical results of a new technique involving raising and replacing of an epithelial flap in photorefractive keratectomy . METHODS: A prospective, non-randomised, comparative, paired eye trial was performed in 72 eyes of 36 patients who underwent PRK with a Nidek EC-5000 excimer laser . For epithelial debridement before PRK, the eyes were divided into two groups . The first eye of each patient was treated with 20% ethanol debridement and the second eye with an epithelial flap which was replaced after treatment . PRK was carried out with the same laser and nomogram in both groups by the same surgeon . Visual and refractive outcome of PRK treatment was compared in both groups . RESULTS: The mean (SD) preoperative mean spherical equivalent (MSE) was -3.61 (1.38) dioptres (D) (range -1.00 D to -7.88 D) with no significant difference between the two groups . After a mean follow up period of 62.6 weeks (range 52-70) the final MSE was +0.07 (0.61) D (range -5.50 D to +4.50 D) in the debridement group and -0.24 (0.43) D in the epithelial flap group . There was no statistically significant difference between the two groups in postoperative MSE . The best corrected visual acuity was better in the epithelial flap group at all visits; this difference was statistically significant (p<0.05) . The corneal haze was less in the epithelial flap group and this difference was also statistically significant (p<0.05) . CONCLUSIONS: Managing the corneal epithelium as a hinged flap with 20% ethanol is a safe technique with faster visual rehabilitation and reduced haze compared with debridement of the epithelium with alcohol . Further studies need to be performed to compare pain levels postoperatively with the epithelial flap and epithelial debridement.

Clin Infect Dis, 2001 Apr 1, 32(7), 1024 - 33 Epub 2001 Mar 19.
Current understanding and management of chronic hepatosplenic suppurative brucellosis; Ariza J et al.; To outline the characteristics and define appropriate management of chronic hepatosplenic suppurative brucellosis (CHSB), 905 patients with brucellosis were analyzed . Sixteen episodes of CHSB (14 in the liver and 2 in the spleen) were found in 15 patients . Six patients had had previous remote brucellosis . Twelve patients presented with systemic symptoms, and 12 with local symptoms . Cultures of blood samples yielded negative results in all cases except 1, and the results of cultures of pus specimens were positive for Brucella melitensis in only 2 cases . All patients showed calcium deposits surrounded by a hypodense area on computed tomography . Patients often had low titers of agglutinating antibody . In patients who were receiving conservative management, early response was successful in 50% and late response was successful in 33.3% . In the patients who underwent surgery and concomitant antibiotic therapy, early and late response was successful in 100% . Thus, CHSB mainly represents a local reactivation of previous brucellosis . Its diagnosis may be difficult to establish and surgery may be required to cure many patients.

J Anim Sci, 2001 Mar, 79(3), 658 - 65
National market cow and bull beef quality audit-1999: a survey of producer-related defects in market cows and bulls; Roeber DL et al.; The 1999 National Market Cow and Bull Beef Quality Audit comprised face-to-face interviews with industry representatives (n = 49); in-plant evaluations of cattle in holding pens (n = 3,969), carcasses on harvest floors (n = 5,679), and in carcass coolers (n = 4,378); and a strategy workshop . Face-to-face interviews suggested that the beef industry was most frequently concerned about the presence of antibiotic residues in carcasses, presence of lead shot in carcasses, and price discovery for carcasses following excessive trimming of bruises and testing due to arthritic joints, pathogens, or antibiotic residues . Although live animal evaluations determined that 73.4% of beef cows, 60.8% of dairy cows, 63.7% of beef bulls, and 70.9% of dairy bulls did not exhibit evidence of lameness, losses due to lameness were greater (P < 0.05) than in the 1994 National Non-Fed Beef Quality Audit . In-plant audits revealed that 88.9, 10.3, and 88.2% of cow carcasses and 18.9, 21.2, and 52.9% of bull carcasses had inadequate muscling, arthritic joints, and at least 1 bruise, respectively, all of which resulted in greater (P < 0.05) losses than the same defects in 1994 . Audits revealed that 88.9% of cow carcasses and 18.9% of bull carcasses were lightly muscled, resulting in greater (P < 0.05) losses for cow carcasses, and similar (P > 0.05) losses for bull carcasses, than the same defect in the 1994 audit . Also, 14.5 and 30.8% of cow carcasses and 6.9 and 5.9% of bull carcasses had excess external fat and yellow-colored external fat, respectively, which was an improvement (P < 0.05) over 1994 results . In aggregate, 24.1, 19.2, 7.2, 6.7, 9.5, and 1.1% of livers, tripe, hearts, heads, tongues, and whole cattle or carcasses, respectively, were condemned and 60.6, 2.4, and 46.5% of cattle had hide damage from latent defects, insect damage, and brands, respectively . Condemnation rates were generally lower (P < 0.05), but tongue condemnations and frequency of branded hides were higher (P < 0.05) than in 1994 . Producers should promote value in cows and bulls by managing to minimize quality defects, monitoring health and condition, and marketing in a timely manner . Using these techniques, producers might have recaptured $13.82, $27.50, and $27.50, respectively, for each cow or bull harvested in 1999.

J Org Chem, 2001 Mar 9, 66(5), 1708 - 15
The first total synthesis of concanamycin f (concanolide a); Toshima K et al.; A highly stereoselective total synthesis of the macrolide antibiotic concanamycin F (1), a specific and potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 18-membered tetraenic lactone and beta-hydroxyl hemiacetal side chain subunits . The C1-C19 18-membered lactone aldehyde 4 was synthesized through the intermolecular Stille coupling of the C5-C13 vinyl iodide 24 and the C14-C19 vinyl stannane 25, followed by construction of the C1-C4 diene and macrolactonization . Synthesis of 4 via a second convergent route including the esterification of the C1-C13 vinyl iodide 45 and the C14-C19 vinyl stannane 47 followed by the intramolecular Stille coupling was also realized . The highly stereoselective aldol coupling of 4 and the C20-C28 ethyl ketone 5 followed by desilylation provided 1 which was identical with natural concanamycin F.

Ann Neurol, 2001 Mar, 49(3), 345 - 54
Sequence-selective DNA binding drugs mithramycin A and chromomycin A3 are potent inhibitors of neuronal apoptosis induced by oxidative stress and DNA damage in cortical neurons; Chatterjee S et al.; Global inhibitors of RNA or protein synthesis such as actinomycin D or cycloheximide abrogate neuronal apoptosis induced by numerous pathological stimuli in vitro and in vivo . The clinical application of actinomycin D or cycloheximide to human neurological disease has been limited by the toxicities of these agents . To overcome these toxicities, strategies must be developed to inhibit selectively the expression of deleterious proapoptotic proteins, while leaving the expression of antiapoptotic, proregeneration, and other critical homeostatic proteins unperturbed . Mithramycin A (trade name Plicamycin) is an aureolic acid antibiotic that has been used in humans to treat hypercalcemia and several types of cancers . This class of agents is believed to act, in part, by selectively inhibiting gene expression by displacing transcriptional activators that bind to G-C-rich regions of promoters . Here we demonstrate that mithramycin A and its structural analog chromomycin A3 are potent inhibitors of neuronal apoptosis induced by glutathione depletion-induced oxidative stress or the DNA-damaging agent camptothecin . We correlate the protective effects of mithramycin A with its ability to inhibit enhanced DNA binding of the transcription factors Sp1 and Sp3 to their cognate "G-C" box induced by oxidative stress or DNA damage . The protective effects of mithramycin A cannot be attributed to global inhibition of protein synthesis . Together, these results suggest that mithramycin A and its structural analogs may be effective agents for the treatment of neurological diseases associated with aberrant activation of apoptosis and highlight the potential use of sequence-selective DNA-binding drugs as neurological therapeutics.

Drug Metab Dispos, 2001 Apr, 29(4 Pt 1), 453 - 9
Uptake of teicoplanin by isolated rat hepatocytes: comparison with in vivo hepatic distribution; Reinoso RF et al.; Tissue distribution of teicoplanin, a large glycopeptide antibiotic, is slow but at equilibrium its whole body distribution volume is relatively large (Vss = 1.18-2.78 liter/kg), despite a high binding to plasma albumin . In vivo distribution into liver is extensive . Previous in vitro homogenate studies suggest that teicoplanin binds to cell membranes but only enters some cells . This possibility was investigated with isolated hepatocytes incubated for 4 h with {14C}teicoplanin alone and in the presence of additional teicoplanin (1 and 100 microg/ml) . Uptake was determined after separating the cells by rapid centrifugation through a dibutyl phthalate layer and assessing viability by the trypan blue exclusion test . Teicoplanin cell uptake curves, initially rapid followed by slower distribution (which agrees with in vivo findings), were adequately described by a closed two-compartment model . Whereas entry into hepatocytes was independent of drug concentration, binding to the cell exterior membrane was concentration-dependent . The equilibrium distribution ratio (Kpu(c) +/- S.D.; 42 +/- 10) was somewhat smaller than estimated in vivo (106 +/- 9), but similar to that reported previously in vitro using liver homogenates (54 +/- 11) . Also, the estimated membrane permeability-surface area product was larger in vitro than in vivo (PSu +/- S.D.; 5.5 +/- 2.9 versus 0.74 +/- 0.10 ml/min per whole liver) . The most likely explanation for this difference is that in vivo only a small fraction of the total cell surface area is exposed to the perisinusoidal space, where exchange occurs.

Ann Allergy Asthma Immunol, 2001 Feb, 86(2), 219 - 21
Patients receiving immunotherapy report it is effective as assessed by the rhinitis outcomes questionnaire (ROQ) in a private practice setting; Santilli J et al.; BACKGROUND: Outcomes measurement is a proficient method in determining the effectiveness of medical therapy . Currently, there are no easy-to-use and inexpensive questionnaires available to evaluate the effectiveness of immunotherapy by allergists in private practice . OBJECTIVE: To evaluate the effectiveness of immunotherapy in the treatment of patients with allergic rhinitis in a private practice setting using the rhinitis outcomes questionnaire (ROQ) . METHODS: One hundred seventy-five patients were randomly chosen from three private practices nationwide . They were surveyed regarding global systemic problems and nasal, eye, and chest symptoms, as well as their medical treatment history . This questionnaire was administered twice in one sitting, with the first a recall of symptoms before immunotherapy treatment, and the second an evaluation of current symptoms . RESULTS: The data revealed that 81% of the patients believed immunotherapy worked, with 19% unsure . Patients experienced a 67% decrease in antibiotic use, a 68% decrease in emergency room visits, a 75% decrease in days lost from work or school, and a 79% decrease in hospital admissions . The average symptom score reduction with immunotherapy was 52% . CONCLUSIONS: This study demonstrates that the user-friendly ROQ can be effectively and inexpensively used in a private practice setting and that immunotherapy is effective in the treatment of allergic rhinitis.

Am J Rhinol, 2001 Jan-Feb, 15(1), 49 - 53
Efficacy of endoscopic sinus surgery in the management of patients with asthma and chronic sinusitis; Palmer JN et al.; An association between chronic sinusitis and asthma has been noted for many years, although the precise nature of the relationship is poorly understood . Earlier studies, using traditional surgical techniques, have demonstrated subjective improvement in asthmatic complaints . Reports demonstrating improvement following endoscopic sinus surgery for chronic sinusitis are rare . To report our experience with endoscopic sinus surgery and asthmatics, we reviewed the charts of 75 consecutive patients with asthma and chronic sinusitis who underwent endoscopic sinus surgery between 1994 and 1996 . Study criteria included the following: chronic sinusitis, one year preoperative and one year postoperative follow-up from endoscopic sinus surgery, and asthma requiring inhaled steroids and oral prednisone for control . Many patients required prednisone bursts for control of asthma . Number of days and total dose of oral prednisone were used as objective measures of asthma control . Number of weeks of antibiotics was used as a relative measure of sinusitis . Fourteen of the 15 patients meeting study criteria decreased their postoperative prednisone requirement by total number of days (preoperative 84 versus postoperative 63 days {p < 0.0001}) . Postoperatively, patients required an average of 1300 mg less oral prednisone (p < 0.033) . Antibiotic use also decreased, with an average use of antibiotic nine weeks preoperatively versus seven weeks postoperatively (p < 0.045) . This study provides corroborative objective evidence that, at least in the short term, endoscopic sinus surgery is efficacious in the management of patients with chronic sinusitis and asthma.

Biochim Biophys Acta, 2001 Mar 9, 1546(1), 44 - 54
Active site structure of the catalase-peroxidases from Mycobacterium tuberculosis and Escherichia coli by extended X-ray absorption fine structure analysis; Powers L et al.; The catalase-peroxidase encoded by katG of Mycobacterium tuberculosis is a more effective activator of the antibiotic isoniazid than is the equivalent enzyme from Escherichia coli . The environment of the heme iron was investigated using X-ray absorption spectroscopy to determine if differences in this region were associated with the differences in reactivity . The variation in the distal side Fe-ligand distances between the two enzymes was the same within experimental error indicating that it was not the heme iron environment that produced the differences in reactivity . Analysis of variants of the E . coli catalase-peroxidase containing changes in active site residues Arg102 and His106 revealed small differences in Fe-water ligand distance including a shorter distance for the His106Tyr variant . The Arg102Leu variant was 5-coordinate, but His106Cys and Arg102Cys variants showed no changes within experimental error . These results are compared with those reported for other peroxidases.

Br J Gen Pract, 2001 Mar, 51(464), 177 - 81
Symptoms, signs, and prescribing for acute lower respiratory tract illness; Holmes WF et al.; BACKGROUND: Most patients who consult with acute lower respiratory symptoms receive antibiotics, usually without evidence of significant infection . The physical signs at presentation of acute lower respiratory tract illness and the rate at which symptoms resolve and normal activities recover is not well documented . AIM: To examine in patients with lower respiratory tract infection (LRTi), their physical signs at presentation, their relationship to antibiotic prescribing, and symptom resolution and resumption of normal activities . DESIGN OF STUDY: Analysis of data collected prospectively during presentation of acute LRTi in primary care and from patient symptom diary cards . SETTING: Forty GPs who were members of an informal Community Respiratory Infection Interest Group recruited 391 patients to the study . METHOD: Information was collected on pulse, oral temperature, respiratory rate, abnormalities on auscultation, and details of any antibiotic prescription . Patients completed symptom diary cards for the following 10 days . RESULTS: Of the 391 patients who consulted 71% received antibiotics . A minority had abnormal physical signs: 17% had a pulse greater than 90 bpm, 15% a respiratory rate greater than 20 breaths per minute, 4% had a temperature greater than 38 degrees C, and 25% had an abnormality on auscultation . Antibiotic prescribing was more common in the presence of abnormal chest signs (odds ratio = 8.71, 95% confidence interval = 3.69-20.61) or discoloured sputum (OR = 2.67, 95% CI = 1.57-4.56) . Ten days after consultation, 58% of patients were still coughing and 29% had not returned to normal activities . CONCLUSION: Abnormal physical signs at presentation do not explain the high rates of antibiotic prescribing nor do they predict persisting cough and functional impairment at 10 days . Reconsultation for the same symptoms within a month is common and is strongly related to persisting cough, but not abnormalities at presentation.

Arch Otolaryngol Head Neck Surg, 2001 Mar, 127(3), 281 - 6
Management of orbital subperiosteal abscess in children; Rahbar R et al.; OBJECTIVES: To present guidelines for the management of an orbital subperiosteal abscess (SPA) in children and to assess the efficacy and safety of transnasal endoscopic drainage of an orbital SPA . SETTING: Tertiary care children's hospital . PATIENTS: Nineteen patients treated for an SPA between July 1997 and December 1999 . The age of the patients ranged from 17 months to 14 years (mean, 6 years) . The male-female ratio was 10:9 . Treatment modalities included transnasal endoscopic drainage (n = 11), external drainage (n = 3), and intravenous antibiotics alone (n = 5) . RESULTS: Bilateral pansinusitis was the most common cause . All patients received an initial trial of intravenous antibiotics . Based on the Fisher exact test, no statistically significant differences were detected for age, sex, presence of gaze restriction, and radiographic findings . Based on multiple logistic regression, degree of proptosis was the only significant multivariate predictor of surgery (P =.003) . The estimated probability of surgery was 6% when there was no proptosis, and 92% for 2 mm of proptosis . The location of the SPA determined the route of surgical drainage . Eleven patients with a medially based SPA underwent drainage via the transnasal endoscopic approach, and 3 with a superior SPA underwent drainage externally . The external approach was associated with a longer hospital stay (median, 7 days) than either the endoscopic or the intravenous antibiotic approach (median, 5 days).

Z Geburtshilfe Neonatol, 2001 Jan-Feb, 205(1), 20 - 6
{Emergency cervix cerclage in amniotic sac prolapse--a realistic option for prolonging pregnancy}; Hitschold T et al.; BACKGROUND: We tried to evaluate, whether emergency operative closure of the cervix (EOCC) is a realistic option for prolongation of pregnancy in cases with early opening of the cervix and prolapse of the amniotic sac (PAS) into the vagina . PATIENTS AND METHODS: We report on 16 patients with PAS between 15 + 3 and 28 + 1 weeks of gestation and cervix dilatation between 2 and 8 cm . After antibiotic and tocolytic treatment we performed EOCC in 7 cases and EOCC + Cerclage in 9 cases . Pregnancy follow up and fetal outcome were analysed retrospectively . RESULTS: Mean gestational age at delivery was 33 + 1 weeks (9 cases > 32 + 0 weeks, 2 cases between 28 + 0 and 31 + 6 weeks, 3 cases between 25 + 0 and 27 + 6 weeks, 1 case with rupture of membranes during operation and immediate cesarean section at 28 + 1 weeks, 1 miscarriage at 23 + 3 weeks) . Time between EOCC and delivery was between 0 and 146 days (mean 56.3 days), 14 fetuses survived healthy . The best results were obtained after EOCC + cerclage . CONCLUSION: If antibiotic and tocolytic treatment was successful in stopping local infection and contractions, EOCC is an acceptable and mostly successful procedure to prolong pregnancy.

Arch Intern Med, 2001 Mar 12, 161(5), 722 - 7
Early switch and early discharge strategies in patients with community-acquired pneumonia: a meta-analysis; Rhew DC et al.; BACKGROUND: The effectiveness of early switch and early discharge strategies in patients with community-acquired pneumonia remains unknown . METHODS: We searched the MEDLINE, HEALTHSTAR, EMBASE, Cochrane Collaboration, and Best Evidence databases from January 1, 1980, to March 31, 2000, for community-acquired pneumonia studies that included specific switch criteria or recommendations to switch on a particular day . RESULTS: From 1794 titles identified, 121 articles were reviewed . We identified 10 prospective, interventional, community-acquired pneumonia-specific studies that evaluated length of stay (LOS) . Nine studies applied an early switch from parenteral to oral antibiotic criteria . Six different criteria for switching were applied in the 9 studies . Five of the studies that applied early switch criteria also applied separate criteria for early discharge . Six studies applied an early switch and early discharge strategy to an intervention and control group, and 5 of these provided SD values for LOS . The mean change in LOS was not significantly (P =.05) reduced in studies of early switch and early discharge (-1.64 days; 95% confidence interval, -3.30 to 0.02 days) . However, when the 2 studies in which the recommended LOS was longer than the control LOS were excluded from the analysis, the mean change in LOS was reduced by 3 days (-3.04 days; 95% confidence interval, -4.90 to -1.19 days) . Studies did not reveal significant differences in clinical outcomes between the intervention and control groups . CONCLUSIONS: There is considerable variability in early switch from parenteral to oral antibiotic criteria for patients with community-acquired pneumonia . Early switch and early discharge strategies may significantly and safely reduce the mean LOS when the recommended LOS is shorter than the actual LOS.

J Antimicrob Chemother, 1999 Feb, 43(2), 227 - 32
Amphotericin B susceptibility testing of Candida lusitaniae isolates by flow cytofluorometry: comparison with the Etest and the NCCLS broth macrodilution method; Favel A et al.; A flow cytofluorometric susceptibility test (FCST) was used for rapid determination of the susceptibility of Candida lusitaniae isolates to amphotericin B . The test is based on the decrease in fluorescence intensity of cells stained with 3,3'-dipentyloxacarbocyanine iodide (DiOC5(3)), a membrane potential-sensitive cationic dye, after drug treatment . A total of 58 C . lusitaniae clinical isolates including strains known to be amphotericin B-resistant on the basis of in-vivo and/or in-vitro data were tested . MICs were determined concurrently by the NCCLS broth macrodilution method and the Etest, both with antibiotic medium 3 . Regression analysis demonstrated that the data from the FCST and the Etest were better correlated (r = 0.93, n = 59, P < 0.001) than those from the FCST and the NCCLS method (r = 0.63, n = 59, P < 0.001) . The FCST readily identified a series of putatively susceptible and resistant isolates . Our study points out the advantages of the flow cytometry approach in antifungal susceptibility testing of yeasts, since speed remains a major problem in conventional tests.

Chem Biol, 2001 Feb, 8(2), 207 - 20
Role of type II thioesterases: evidence for removal of short acyl chains produced by aberrant decarboxylation of chain extender units; Heathcote ML et al.; BACKGROUND: Modular polyketide synthases (PKSs) function as molecular assembly lines in which polyketide chains are assembled by successive addition of chain extension units . At the end of the assembly line, there is usually a covalently linked type I thioesterase domain (TE I), which is responsible for release of the completed acyl chain from its covalent link to the synthase . Additionally, some PKS clusters contain a second thioesterase gene (TE II) for which there is no established role . Disruption of the TE II genes from several PKS clusters has shown that the TE II plays an important role in maintaining normal levels of antibiotic production . It has been suggested that the TE II fulfils this role by removing aberrant intermediates that might otherwise block the PKS complex . RESULS: We show that recombinant tylosin TE II behaves in vitro as a TE towards a variety of N-acetylcysteamine and p-nitrophenyl esters . The trends of hydrolytic activity determined by the kinetic parameter k(cat)/K(M) for the analogues tested indicates that simple fatty acyl chains are effective substrates . Analogues that modelled aberrant forms of putative tylosin biosynthetic intermediates were hydrolysed at low rates . CONCLUSIONS: The behaviour of tylosin TE II in vitro is consistent with its proposed role as an editing enzyme . Aberrant decarboxylation of a malonate-derived moiety attached to an acyl carrier protein (ACP) domain may generate an acetate, propionate or butyrate residue on the ACP thiol . Our results suggest that removal of such groups is a significant role of TE II.

Eur J Cardiothorac Surg, 2001 Mar, 19(3), 302 - 6
Expanded polytetrafluoroethylene membranes to wrap surfaces of circulatory support devices in patients undergoing bridge to heart transplantation; Leprince P et al.; OBJECTIVE: Because of a lack of donor hearts, an increasing number of patients with heart failure must now undergo bridge to cardiac transplantation with a mechanical circulatory support device . Moreover, support periods have become longer . As a result, pericardial adhesions may develop while the support device is implanted, increasing the risk of injury at resternotomy and bleeding after transplantation . Use of expanded polytetrafluoroethylene (ePTFE) pericardial substitutes (membranes) may prevent such adhesions . PATIENTS AND METHODS: From January 1997 to December 1999, ePTFE membranes were used in 23 patients to wrap portions of an implanted left ventricular assist device (LVAD) or total artificial heart (TAH) . Any complications during mechanical support or at cardiac transplantation were recorded . Six ePTFE membranes removed at transplantation were studied histologically . RESULTS AND CONCLUSIONS: At resternotomy for transplantation, the plane of dissection between tissues, ePTFE membranes, and surfaces of the mechanical support device were easily discerned . No adhesions were observed between tissues and membranes . There were no injuries during resternotomy and no patient had to undergo reoperation because of bleeding . One patient given a TAH had an infection during circulatory support that was controlled by antibiotic therapy . In another patient, clots developed between the device and an ePTFE membrane; these were removed successfully . Histologic studies of removed ePTFE membranes showed no infiltration of the membranes interstices by collagen or cellular components . Use of ePTFE membranes in patients undergoing bridge to transplantation with either an LVAD or a TAH limited adhesions between tissues and device surfaces without increasing the risk of infection.

Curr Opin Investig Drugs, 2000 Sep, 1(1), 52 - 7
Pazufloxacin Toyama Chemical Co; Johnson AP; Toyama Chemical Co Ltd is developing pazufloxacin (T-3761), an orally active synthetic quinolone antibiotic, which is awaiting registration following successful clinical trials that demonstrated its pharmacological similarities to tosufloxacin (Toyama Chemical Co) with respect to clinical efficacy, adverse effects and overall safety {272136} . As of June 2000, the company had filed an NDA for marketing approval in Japan {373027} . The company is also developing an injectable formulation, pazufloxacin mesylate (T-3762), which has entered phase III trials in Japan {228819} . There is a licensing agreement with Welfide Corp (formerly Yoshitomi/The Green Cross Corp) in Japan {228819}.

Curr Opin Investig Drugs, 2000 Sep, 1(1), 31 - 4
Olamufloxacin . Hokuriku Seiyaku; Jiraskova N; Hokuriku is developing olamufloxacin, a quinolone antibiotic that inhibits DNA gyrase, for the potential treatment of various types of bacterial infection . It has reached late phase II clinical trials . An intravenous formulation is also under investigation {277817}.

Bioorg Med Chem, 2001 Feb, 9(2), 357 - 65
Rebeccamycin analogues from indolo{2,3-c}carbazole; Voldoire A et al.; Glycosylated indolocarbazoles related to the antibiotic rebeccamycin represent an important series of antitumor drugs . In the course of structure-activity relationship studies, we report the synthesis of two new derivatives containing an indolo{2,3-c}carbazole chromophore instead of the conventional indolo{2,3-a}carbazole unit found in the natural metabolites . The N-methylated compound 8 containing one glucose residue behaves as a typical DNA intercalating agent, as judged from circular and electric linear dichroism measurements with purified DNA . In contrast, the bis-glycosylated derivative 7 containing a glucose residue on each indole nitrogen has lost its capacity to form stable complexes with DNA . DNA relaxation experiments reveal that the two drugs 7 and 8 have weak effects on human DNA topoisomerase I . The modified conformation of the indolocarbazole chromophore is detrimental to the stabilization of topoisomerase I-DNA complexes . The lack of potent topoisomerase I inhibition leads to decreased cytotoxicity but, however, we observed that the DNA-intercalating mono-glycosyl derivative 8 is about 5 times more cytoxic than the bis-glycosyl analogue 7 . The study suggests that the naturally-occurring indolo{2,3-a}carbazole skeleton should be preserved to maintain the topoisomerase I inhibitory and cytotoxic activities.

Cornea, 2001 Mar, 20(2), 179 - 82
Topical bactrim versus trimethoprim and sulfonamide against nocardia keratitis; Lee LH et al.; PURPOSE: The conventional treatment of Nocardia keratitis is with topical sulfonamides . Recently, topical trimethoprim and sulfamethoxazole (Bactrim) has been suggested as treatment . This study compares the in vitro efficacy against Nocardia asteroides of Bactrim and various ratios of trimethoprim and a sulfonamide . METHODS: Antibiotic disks were soaked with various ratios of trimethoprim and sulfacetamide sodium . They contained trimethoprim alone, sulfacetamide sodium alone, and both trimethoprim and sulfacetamide sodium at ratios of 1:40, 1:20, and 1:5 . Disks containing Bactrim were also prepared . Each disk was placed on blood agar plates streaked with N . asteroides . The plates were incubated at 37 degrees C for 72 hours and then examined . RESULTS: Trimethoprim alone showed minimal effect . Sulfacetamide sodium alone had a clearance zone of 12 mm . The plates of trimethoprim and sulfacetamide sodium at ratios of 1:40, 1:20, and 1:5 had clearance zones of 14 mm, 17 mm, and 27 mm, respectively . Bactrim had a clearance zone of 70 mm . CONCLUSION: Trimethoprim or sulfacetamide sodium alone is not as effective as both drugs together . As the ratio of the two drugs was changed, potency differed against Nocardia organisms . Bactrim was the most effective antibiotic against Nocardia organisms . It should be the recommended agent for the treatment of Nocardia keratitis.

Eur J Biochem, 2001 Mar, 268(6), 1712 - 21
Cyclic dipeptide oxidase from Streptomyces noursei . Isolation, purification and partial characterization of a novel, amino acyl alpha,beta-dehydrogenase; Gondry M et al.; Cyclic dipeptide oxidase is a novel enzyme that specifically catalyzes the formation of alpha,beta-dehydro-Phe (Delta Phe) and alpha,beta-dehydro-Leu (Delta Leu) residues during the biosynthesis of albonoursin, cyclo(Delta Phe-Delta Leu), an antibiotic produced by Streptomyces noursei . It was purified 600-fold with a 30% overall recovery, and consists of the association of a single type of subunit with a relative molecular mass of 21,066 resulting in a large homopolymer of relative molecular mass over 2,000,000 . The enzyme exhibits a typical flavoprotein spectrum with maxima at 343.5 and 447.5 nm, the flavin prosthetic group being covalently bound to the protein . The catalytic reaction of the natural substrate cyclo(L-Phe-L-Leu) occurs in a two-step sequential reaction leading first to cyclo(alpha,beta-dehydro-Phe-L-Leu) and finally to albonoursin . Kinetic parameters for the first step were determined (K(m) = 53 microM; k = 0.69 s(-1)) . The enzyme was shown to catalyze the conversion of a variety of cyclo(dipeptides) and can be reoxidized at the expense of molecular oxygen by producing H(2)O(2) . This reaction mechanism, which differs from those already described for the formation of alpha,beta-dehydro-amino acids, might consist of the transient formation of an intermediate imine followed by its rearrangement into an alpha,beta-dehydro-residue.

J Pharm Biomed Anal, 2001 Mar, 24(5-6), 1111 - 23
Thermal stability of disodium and calcium phosphomycin and the effects of the excipients evaluated by thermal analysis; Vecchio S et al.; In the present study, Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC) are simultaneously applied to determine the thermal properties of two antibiotic salts, disodium and calcium phosphomycin, used either pure or in association with several excipients . This study was carried out kinetically as well by mathematical elaboration of the TG curves performed according to an isothermal procedure applied at different fixed temperatures . Kinetic parameters showing agreement with those produced by the isothermal method were also obtained by means of a non-isothermal method using a dynamic TG curve alone . The main aims of the work were to provide reliable kinetic parameters (kinetic constant k, activation energy E(a) and pre-exponential factor A) to evaluate the thermal stability of phosphomycin salts in the presence and absence of the excipients generally contained in the phosphomycin-based pharmaceutical forms available on the market, and to obtain information concerning compatibility towards the active components . These kinetic parameters were then used to extrapolate shelf-life and half-life values at room temperature for pure active components in the solid state and for their pharmaceutical derivatives.

Biomaterials, 2001 Apr, 22(7), 701 - 8
Bioactivity in glass/PMMA composites used as drug delivery system; Arcos D et al.; Gentamicin sulfate has been incorporated in composites prepared from a SiO2-CaO-P2O5 bioactive glass and polymethylmethacrylate . Data showed that these materials could be used as drug delivery system, keeping the bioactive behavior of the glass . The composites supply high doses of the antibiotic during the first hours when they are soaked in simulated body fluid (SBF) . Thereafter, a slower drug release is produced, supplying 'maintenance' doses until the end of the experiment . The gentamicin release rate is related with the ionic Ca2+ and H3O+ exchange between composite and SBF . The porous structure of the composites allows the growth of hydroxycarbonate apatite on the surface and into the pores.

Nihon Kokyuki Gakkai Zasshi, 2000 Dec, 38(12), 937 - 42
{A case of limited Wegener granulomatosis with hypereosinophilia}; Tsushima K et al.; A 51-year-old female was admitted to Nagano Matsushiro General Hospital because of fever, cough and dyspnea on exertion . Her laboratory data revealed leukocytosis with hypereosinophilia, a high erythrocyte sedimentation rate and c-reactive protein . Chest radiography revealed an infiltration shadow with a cavity in the right upper lobe . A lung abscess was diagnosed and antibiotics were administered . Laboratory results showed improvement, but chest radiography continued to show cavities . She was admitted to our hospital because of fever, left pleural effusion and progression of cavities on chest radiographs . She showed no abnormalities of the upper airway or kidney, and was negative for c-antineutrophil cytoplasmic antibody (c-ANCA) . Because a positive c-ANCA was seen on day 8 of hospitalization, L-type limited Wegener granulomatosis (WG) was diagnosed according to Gross et al . Prednisolone (PSL) was administered, which improved the anemia, eosinophilia and the cavities . On day 7 of PSL administration, of the left pneumothorax occurred as a complication caused by perforation of the left chest cavity, but her clinical course was good after a cavernectomy was performed . Some studies have reported that limited WG shows a negative c-ANCA, and that antibiotic therapy improves inflammation . The L-type of limited WG revealed a low-grade positive ratio and titer of c-ANCA . Moreover, L-type limited WG responds well to therapy . We therefore selected PSL administration only against L-type limited WG . We have reported L-type limited WG with eosinophilia and the negative effects of c-ANCA at an early clinical stage.

J Bacteriol, 2001 Apr, 183(7), 2198 - 203
Modulation of actinorhodin biosynthesis in Streptomyces lividans by glucose repression of afsR2 gene transcription; Kim ES et al.; While the biosynthetic gene cluster encoding the pigmented antibiotic actinorhodin (ACT) is present in the two closely related bacterial species, Streptomyces lividans and Streptomyces coelicolor, it normally is expressed only in S . coelicolor-generating the deep-blue colonies responsible for the S . coelicolor name . However, multiple copies of the two regulatory genes, afsR and afsR2, activate ACT production in S . lividans, indicating that this streptomycete encodes a functional ACT biosynthetic pathway . Here we report that the occurrence of ACT biosynthesis in S . lividans is determined conditionally by the carbon source used for culture . We found that the growth of S . lividans on solid media containing glucose prevents ACT production in this species by repressing the synthesis of afsR2 mRNA; a shift to glycerol as the sole carbon source dramatically relieved this repression, leading to extensive ACT synthesis and obliterating this phenotypic distinction between S . lividans and S . coelicolor . Transcription from the afsR2 promoter during growth in glycerol was dependent on afsR gene function and was developmentally regulated, occurring specifically at the time of aerial mycelium formation and coinciding temporally with the onset of ACT production . In liquid media, where morphological differentiation does not occur, ACT production in the absence of glucose increased as S . lividans cells entered stationary phase, but unlike ACT biosynthesis on solid media, occurred by a mechanism that did not require either afsR or afsR2 . Our results identify parallel medium-dependent pathways that regulate ACT biosynthesis in S . lividans and further demonstrate that the production of this antibiotic in S . lividans grown on agar can be modulated by carbon source through the regulation of afsR2 mRNA synthesis.

Am Surg, 2001 Feb, 67(2), 105 - 10
Identification of early predictors for post-traumatic pneumonia; Croce MA et al.; We demonstrated that the standard clinical criteria of fever, leukocytosis, purulent sputum, and infiltrate on chest radiograph are nonspecific for the diagnosis of post-traumatic pneumonia, and only approximately 50 per cent of patients with these conditions have pneumonia . Quantitative cultures of bronchoalveolar lavage effluent will differentiate pneumonia (requiring antibiotic therapy) from systemic inflammatory response syndrome (not requiring antibiotics) . Early identification of patients at risk for pneumonia can target populations for clinical research . Because risk factors for pneumonia when diagnosed by quantitative cultures have not been defined we reviewed our recent experience to identify variables predictive of pneumonia . Patients over a 22-month period who survived > 48 hours were identified from the trauma registry . Pneumonia was defined as growth of > or = 10(5) organisms per milliliter in the bronchoalveolar lavage effluent . Risk factors evaluated included injury severity and severity of shock . There were 7503 patients (75% with blunt and 25% with penetrating injuries) . The incidence of pneumonia was 6 per cent (7% of patients with blunt and 2% of patients with penetrating injuries) . Logistic regression analysis identified age; Glasgow Coma Scale score; Injury Severity Score; transfusion requirements during resuscitation; spinal cord injury; chest injury severity; and emergent femur fixation, craniotomy, and laparotomy as being independent predictors of pneumonia . We conclude that multiple risk factors, which are all able to be determined early after injury, are predictive of post-traumatic pneumonia . Prompt identification of this high-risk group of patients allows prognostic considerations relative to patient management schemes and targets populations for prophylactic measures or immunomodulation.

Rev Stomatol Chir Maxillofac, 2000 Dec, 101(6), 330 - 5
{Chronic diffuse osteomyelitis of the mandible . Apropos of a case}; Lemiere E et al.; The incidence of osteomyelitis of the jaw has declined . Outcome is favorable with antibiotic therapy and surgery . We report a case in a women who experienced an unfavorable course with massive progressive diffusion, complicated by neoplastic conversion.

Ann Intern Med, 2001 Mar 6, 134(5), 380 - 6
Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated; Ohkusa T et al.; BACKGROUND: Glandular atrophy and intestinal metaplasia are precancerous lesions; whether Helicobacter pylori eradication affects these lesions is controversial . OBJECTIVE: To determine whether H . pylori eradication is associated with improvement in glandular atrophy and intestinal metaplasia after at least 1 year . DESIGN: Single-blind, uncontrolled prospective trial . SETTING: Academic gastroenterology clinic in Japan . PATIENTS: 163 consecutive patients with dyspepsia and H . pylori infection . INTERVENTION: One-week course of a proton-pump inhibitor and antibiotic therapy . MEASUREMENTS: Endoscopic examination with antral and corporal biopsy was done before treatment and at 1 to 3 and 12 to 15 months after treatment . Gastritis, atrophy, and metaplasia were graded according to the updated Sydney System . RESULTS: In the 115 patients in whom H . pylori was eradicated, inflammation and mean neutrophil activity had decreased by 1 to 3 months, and both glandular atrophy in the corpus and intestinal metaplasia in the antrum had decreased by 12 to 15 months . Glandular atrophy in the corpus improved in 34 (89%) of 38 patients with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 (61%) of 46 patients who had metaplasia at baseline . In the 48 patients in whom eradication was unsuccessful, no significant histologic changes were observed . CONCLUSION: In the year after successful H . pylori eradication, precancerous lesions improved in most patients.

Spine, 2001 Mar 1, 26(5), 499 - 500
Spondylodiscitis and infective endocarditis: case studies and review of the literature; Morelli S et al.; STUDY DESIGN: This study evaluated the association between infective endocarditis and infective spondylodiscitis and its clinical features . OBJECTIVES: To report case studies of patients with spondylodiscitis complicating infective endocarditis . SUMMARY OF BACKGROUND DATA: Early diagnosis of infective endocarditis as the source of the spondylodiscitis is often difficult because clinical and radiologic patterns are similar to those present in spondylodiscitis alone . METHODS: The case records of the patients with infective endocarditis admitted to our Department from 1991-1998 were reviewed . The diagnosis of spondylodiscitis was made on the basis of clinical features and of typical radiologic signs . RESULTS: Among 30 patients affected by infective endocarditis, three also were affected by spondylodiscitis . All patients fully recovered after appropriate antibiotic therapy . CONCLUSIONS: In all patients with spondylodiscitis, infective endocarditis should be excluded, particularly in patients with a history of heart valve disease.

Clin Pharmacol Ther, 2001 Mar, 69(3), 158 - 68
Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin; Furuta T et al.; BACKGROUND: Proton pump inhibitors such as omeprazole and lansoprazole are mainly metabolized by CYP2C19 in the liver . The therapeutic effects of proton pump inhibitors are assumed to depend on CYP2C19 genotype status . OBJECTIVE: We investigated whether CYP2C19 genotype status was related to eradication rates of H pylori by triple proton pump inhibitor-clarithromycin-amoxicillin (INN, amoxicilline) therapy and attempted to establish a strategy for treatment after failure to eradicate H pylori . METHODS: A total of 261 patients infected with H pylori completed initial treatment with 20 mg of omeprazole or 30 mg of lansoprazole twice a day, 200 mg of clarithromycin three times a day, and 500 mg of amoxicillin three times a day for 1 week . CYP2C19 genotypes of patients were determined with polymerase chain reaction-restriction fragment length polymorphism analysis . Patients without eradication after initial treatment were retreated with 30 mg of lansoprazole four times daily and 500 mg of amoxicillin four times daily for 2 weeks . RESULTS: Eradication rates for H pylori were 72.7% (95% confidence interval, 64.4%-81.8%), 92.1% (confidence interval, 86.4%-97.3%), and 97.8% (confidence interval, 88.5%-99.9%) in the homozygous extensive, heterozygous extensive, and poor metabolizer groups, respectively . Thirty-four of 35 patients without eradication had an extensive metabolizer genotype of CYP2C19 . Nineteen of those patients were infected with clarithromycin-resistant strains of H pylori . However, there were no amoxicillin-resistant strains of H pylori . Re-treatment of H pylori infection with dual high-dose lansoprazole-amoxicillin therapy succeeded in 30 of 31 patients with extensive metabolizer genotype of CYP2C19 . CONCLUSION: The majority of patients without initial eradication of H pylori had an extensive metabolizer CYP2C19 genotype but were successfully re-treated with high doses of lansoprazole and an antibiotic to which H pylori was sensitive, such as amoxicillin, even when the patients were infected with clarithromycin-resistant strains of H pylori.

J Gynecol Obstet Biol Reprod (Paris), 2001 Feb, 30 Suppl 1, 12 - 6
{Premature delivery and inflammation}; Ville Y; Premature delivery results from multiple closely interdependent factors . Inflammation is most generally caused by cervicovaginal infection that may progress to intra-uterine infection or inflammation . Severe chorioamniotitis is found in 75% of all premature deliveries compared with 15% in term deliveries . Premature rupture of the membranes is the cause of premature delivery in 30-40% of premature deliveries although the diagnosis of chorioamniotitis can also be established with intact membranes, sometimes on the basis of histological findings alone . The degree of prematurity is correlated with the severity of the histological chorioamniotitis . The severity and the duration of the lesions is often the cause of antibiotic failure for the treatment of threatening premature delivery . Inflammation mediators, mainly proinflammatory cytokines (IL1, TNF-alpha), chemokines (IL6, IL8 and MIP-1alpha) and immunomodulator cytokines (IL6) and immunosuppressive cytokines (IL10, IL4) are produced by the amniotic and decidual membranes and are found in the fetal circulation and amniotic fluid . This reaction triggers a cascade of events leading to the production of prostaglandins and cyclooxygenase (COX2) activity, that cause uterine contractions . The inflammation may be initiated locally, even from an extrapelvic location, This leads to a fetal and/or maternal systemic inflammatory reaction . Systemic fetal expression of deregulated inflammatory phenomena can lead to neonatal lesions of lung and brain white matter tissue . This explains the failure of tocolysis and antibiotics in uncontrolled situations and suggests new avenues for therapy using selective inhibitors of COX2.

Am J Ophthalmol, 2001 Mar, 131(3), 324 - 31
Multilayered amniotic membrane transplantation for severe ulceration of the cornea and sclera; Hanada K et al.; PURPOSE: To examine the efficacy of amniotic membrane transplantation in the treatment of deep corneal and scleral ulcers . PATIENTS: A total of 11 patients were recruited for this study: four patients (four eyes) with corneal perforation, five patients (five eyes) with a deep corneal ulcer and descemetocele, and two patients (two eyes) with a scleral ulcer . METHODS: Ulcers were treated by amniotic membrane transplantation . Separate amniotic membranes were transplanted as material to fill the stromal layer (amniotic membrane filling), as a basement membrane (amniotic membrane graft), and as a wound cover (amniotic membrane patch) . After surgery, all cases were treated with artificial tears, autologous serum drops, antibiotic eyedrops, topical corticosteroids, and sodium hyaluronate eyedrops . RESULTS: Eight eyes (72.7%) healed with epithelialization in 16.5 +/- 8.0 days (range, 7 to 29 days), with five and three eyes showing corneal epithelialization and conjunctival epithelialization, respectively . A persistent epithelial defect was noted in one eye with corneal ulcer after limbal allograft transplantation for a chemical burn and in two eyes with corneal ulcers as a complication of rheumatoid arthritis . CONCLUSION: Multilayered amniotic membrane transplantation may be effective for the treatment of deep ulceration of the cornea and sclera . In some eyes with total corneal limbal dysfunction or autoimmune disorders, amniotic membrane transplantation alone is not effective.

Indian J Pediatr, 2001 Jan, 68(1), 45 - 51
Management of severe malnutrition and diarrhea; Ahmed T et al.; Children with severe malnutrition and diarrhea have high mortality rates that have been attributed to faulty case-management . Health workers are often unaware of the unique treatment requirements of severely malnourished children resulting in improper case-management . Moreover, the lack of prescriptive guidelines promotes the exercise of discretion in case-management that is often detrimental . Appropriate feeding from the start of treatment, routine micronutrient supplementation, broad-spectrum antibiotic therapy, less use of intravenous fluids for rehydration, and careful management of complications are factors that can reduce death, morbidity and cost of treating children with severe malnutrition and acute illnesses including diarrhea . In this paper is discussed a standardized protocol based upon the above mentioned factors for the management of severely malnourished children with acute illnesses including diarrhea . Implementation of the protocol resulted in a 47% reduction in mortality in these children.

J AOAC Int, 2001 Jan-Feb, 84(1), 134 - 42
Analysis of DDT residues in soil by ELISA: an international interlaboratory study; Maestroni BM et al.; An international interlaboratory study was conducted to determine the performance of a group of laboratories from developing and developed countries . The study used a commercial microwell ELISA on unknown samples spiked with different levels of DDT . The study design was based on Youden pairs and balanced replicates . Two soils, differing in particle size distributions, organic matter content, and cation-exchange capacities and thought to be DDT-free, were spiked at 5 DDT levels between 0.025 and 2 mg/kg . Nineteen laboratories in 17 countries took part in the collaborative trial; of these, the majority were modestly equipped laboratories in developing countries . Samples were analyzed without filtration or cleanup and using standards of pure DDT in methanol . Data were analyzed for repeatability and reproducibility, and average recoveries at the spike levels were calculated . Mean real recoveries for both soils were similar (103% for soil A and 100% for soil B), with values between 0.1 and 2 mg/kg DDT . Precision estimates were best in the linear working range of the assay (0.1-0.5 mg/kg DDT), with reproducibility relative standard deviations (RSDR) typically averaging about 38 and 46% near the upper and lower detection limits, respectively . Corresponding repeatability relative standard deviation (RSDr) values were 20-36% and 36-57% . Thus, even though much of the trial was performed under developing country conditions, performance statistics were similar to other reported results obtained with ELISAs on small molecules of agricultural importance, such as mycotoxins and pesticide and antibiotic residues.

Scand J Infect Dis, 2001, 33(2), 157 - 8
Teicoplanin-induced neutropenia in a paediatric patient with vertebral osteomyelitis; Wee IY et al.; Teicoplanin is a glycopeptide antibiotic that has been used extensively in adults but less so in children for the treatment of bone and joint infections . It has a good safety profile with low incidences of blood dyscrasias . We report a case of teicoplanin-induced neutropenia in a child.

Wien Klin Wochenschr, 2001 Jan 15, 113(1-2), 38 - 44
Borrelia infection as a cause of carditis (a long-term study); Bartunek P et al.; BACKGROUND: Although the frequency of Lyme carditis is not high, it is one of the most challenging conditions in terms of diagnosis . No long-term studies that would help expand our body of knowledge concerning the circumstances of its development and the natural course of this form of Lyme borreliosis (LB), the most widespread anthropozoonosis in Central Europe, have been reported to date . AIM: The authors sought to describe and assess the consequences of a less common form of Lyme carditis (LC) . An assessment of the following aspects was made: a) the forms, natural history and sequelae of the less common clinical appearances of LC, b) the role of antibiotic therapy with reference to the late manifestations of LB . METHODS: Three patients were selected from a group of 60 consecutive patients with demonstrated LC during a follow-up period from 1987 to 2000 . Patient no . 1 was being followed for myocarditis with frequent ventricular extrasystoles, patient no . 2 for pericarditis, and patient no . 3 for dilated cardiomyopathy as a late manifestation of LB . In addition to routine examination at entry, the patients were subjected to a standard 12-lead ECG, continuous 24-hour Holter ECG monitoring, exercise testing (bicycle ergometry), investigations of antibodies using ELISA and Western blot, investigation of thyroid (T3, T4, TSH tests) and mineral levels . RESULTS: The study showed no significant correlation between the clinical course and levels of specific antibodies . It confirmed the concept that inadequate or no therapy with antibiotics in the initial stage of the disease has a significant effect on the development of late sequelae . CONCLUSION: Based on the long-term treatment of three patients with less common, yet clinically urgent findings, the authors conclude that even a relatively serious clinical course is associated with no major limitations for affected individuals after an interval of several years.

Ann Urol (Paris), 2001 Jan, 35(1), 60 - 3
{Prolapse of the urethral mucosa in young girls from the Ivory Coast}; da Silva-Anoma S et al.; In this retrospective study covering a nine-year period, 65 cases have been analyzed of prolapse of the urethral mucosa in young girls (aged between six weeks and 14 years) from the Ivory Coast . The aim of this study was to describe the etiology of this disorder, and to demonstrate the utility of ambulatory surgery . The main reason for the detection of this disorder was mild genital hemorrhage in 37 cases, which was related to rape in eight instances and to other types of trauma in nine cases, thereby raising serious medico-legal problems . Various forms of treatment were used (medical and/or surgical) . The medical approach consisted of antibiotic and antiinflammatory treatment, combined with a local antiseptic . Two surgical approaches were adopted, either the Doria method in which the necrosed tissue is spontaneously eliminated after three to five days, or surgical excision under general anesthesia of the prolapsed mucosa followed by seromucosal stitching . The results were satisfactory in all cases, and in the surgically operated cases no complications or recurrence were noted at one-year follow-up.

Am J Gastroenterol, 2001 Feb, 96(2), 359 - 66
Do some patients with Helicobacter pylori infection benefit from an extension to 2 weeks of a proton pump inhibitor-based triple eradication therapy?
Maconi G, Parente F, Russo A, Vago L, Imbesi V, Porro GB.
OBJECTIVES: Seven-day proton pump inhibitor (PPI)-based triple therapies are the first-line anti-Helicobacter pylori regimens; to date, however, there is still no agreement concerning all the predictors of H . pylori cure under these regimens . The aim of this prospective study was to evaluate whether patients with certain pretreatment characteristics may benefit from an extension from 1 to 2 wk of treatment with lansoprazole, amoxycillin, and clarithromycin . METHODS: A total of 142 patients with H . pylori infection ascertained by means of gastric histopathology and 13C urea breath test (UBT) participated in this study . In all patients H . pylori density was determined at histology both on antral and corpus biopsies, and H . pylori culture with antibiotic susceptibility testing; IgG anti-H . pylori titers were also determined before therapy . Patients were randomized to receive 1-wk versus 2-wk of treatment with lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxycillin (1 g b.i.d.) . The association between eradication and potential predictors was analyzed by means of unconditional logistic regression models and stratified according to the duration of treatment . A stepwise regression analysis was performed to identify variables discriminated between subjects, using eradication status as the dependent variable . RESULTS: The overall eradication rates for 1- and 2-wk treatments were 74.6% and 85.9% (intention-to-treat analysis) and 81.5% and 89.1% (per-protocol analysis), respectively (p = NS) . Multivariate discriminant analysis selected as the variables independently related to eradication cigarette smoking (OR = 3.98), delta of 13C-UBT higher than 35 (OR = 9.21) and IgG anti-H . pylori titer > or = 93 (OR = 0.24) for the whole series of subjects . Stratified analysis according to the duration of therapy selected H . pylori density as the only predictor of eradication in the group treated for 1 wk (OR = 8.11) . In contrast, no significant predictors were found in the group treated for 2 wk . CONCLUSIONS: Patients with a high intragastric bacterial load, as detected by histology (grade 3) or 13C-UBT (delta > 35) may benefit from an extension to 2 wk of triple therapy with lansoprazole, amoxycillin, and clarithromycin.

Nat Biotechnol, 2001 Mar, 19(3), 231 - 4
Inhibition of gene expression in Entamoeba histolytica with antisense peptide nucleic acid oligomers; Stock RP et al.; Peptide nucleic acids (PNAs) may be a potent tool for gene function studies in medically important parasitic organisms, especially those that have not before been accessible to molecular genetic knockout approaches . One such organism is Entamoeba histolytica, the causative agent of amebiasis, which infects about 500 million people and is the cause of clinical disease in over 40 million each year, mainly in the tropical and subtropical world . We used PNA antisense oligomers to inhibit expression of an episomally expressed gene (neomycin phosphorotransferase, NPT) and a chromosomal gene (EhErd2, a homolog of Erd2, a marker of the Golgi system in eukaryotic cells) in axenically cultured trophozoites of E . histolytica . Measurement of NPT enzyme activity and EhErd2 protein levels, as well as measurement of cellular proliferation, revealed specific decreases in expression of the target genes, and concomitant inhibition of cell growth, in trophozoites treated with micromolar concentrations of unmodified antisense PNA oligomers.

Vet Surg, 2001 Mar-Apr, 30(2), 126 - 31
The effect of implanting gentamicin-impregnated polymethylmethacrylate beads in the tarsocrural joint of the horse; Farnsworth KD et al.; OBJECTIVE: To determine the effect of intra-articular gentamicin-impregnated polymethylmethacrylate (PMMA) beads inserted in the equine tarsocrural joint on the synovial fluid, synovial lining, and cartilage, and to determine the peak and sustainable gentamicin concentrations in synovial fluid and plasma . STUDY DESIGN: Pharmacokinetic, cytologic, and histologic study of the effect of gentamicin-impregnated PMMA on normal equine tarsocrural joints . ANIMALS: Five healthy adult horses . METHODS: Gentamicin-impregnated PMMA bead strands (3 strands each of 40 beads, with each strand containing 100 mg gentamicin) were surgically inserted into one radiographically normal tarsocrural joint in 5 horses . Each horse had both joints flushed with 1 L of lactated Ringer's solution before bead administration . Synovial fluid total protein concentration, white blood cell (WBC) count, gentamicin concentration, synovial histology, cartilage integrity, and cartilage glycosaminoglycan (GAG) concentrations were determined . RESULTS: Gentamicin concentration (mean +/- SEM peak concentration, 27.9 +/- 2.27 microg/mL) occurred in the first 24 hours and remained above 2 microg/mL for 9 days . Gentamicin concentrations in control joints and the plasma remained below detectable levels . The synovial fluid WBC count for treated joints was increased compared with control joints for 72 hours, but was similar at day 6 . The synovial protein concentration in gentamicin-treated joints remained increased for 21 days . Synovium in treated joints had diffuse synovitis, whereas control joints had less fibrovascular proliferation . Superficial cartilage erosion was present in all treated joints . There was no difference in the GAG content of treated and control joint cartilage . CONCLUSIONS: Short-term implantation of gentamicin (300 mg)-impregnated PMMA beads can provide therapeutic levels of gentamicin (>2 microg/mL) in the normal tarsocrural joint for 9 days; however, gentamicin-impregnated PMMA beads induce synovitis and superficial cartilage erosion . CLINICAL RELEVANCE: Temporary intra-articular administration of antibiotic-impregnated PMMA may be an effective way to treat septic joints that require constant high concentrations of antibiotics .

Veterinary Clin North Am Exot Anim Pract, 2000 Jan, 3(1), 221 - 37, viii
Rodent therapeutics; Adamcak A et al.; Although the number of rodents kept as pets is increasing in the United States, much of the veterinary information that is known regarding their care is derived from laboratory animal medicine . This article describes individual species variation of medication delivery methods and the associated risks of antibiotic usage . A comprehensive formulary is also included.

Manag Care Interface, 2001 Feb, 14(2), 52 - 9
Workplace costs associated with acute exacerbation of chronic bronchitis: a comparison of moxifloxacin and levofloxacin; Li-McLeod J et al.; Past research on acute exacerbation of chronic bronchitis (AECB) has not quantified related work loss . This exploratory study used data from a comparative trial of moxifloxacin versus levofloxacin to examine and compare workplace-related indirect costs . Both groups reported considerable absenteeism and lowered work productivity . However, patients taking moxifloxacin reported significantly higher work productivity than those taking levofloxacin (70% vs . 50%; P = .03) . This translated into substantial indirect cost savings with moxifloxacin of $726/patient/year . Antibiotic choice in AECB can affect worker productivity and workplace-related indirect costs . Both insurers and employers should consider workplace-related indirect costs in addition to direct medical expenses when making formulary selections.

Can J Vet Res, 2001 Jan, 65(1), 1 - 6
Phenotypic and genotypic characterization of virulence factors of Escherichia coli isolated from broiler chickens with simultaneous occurrence of cellulitis and other colibacillosis lesions; Gomis SM et al.; The objective of this study was to characterize virulence factors of Escherichia coli isolates from broilers with simultaneous occurrence of cellulitis and other colibacillosis lesions . Thirty flocks were sampled and 237 birds with cellulitis were examined . Eighty-two (34.6%) of 237 birds condemned for cellulitis had gross lesions in the heart, air sacs, joints, or liver . In 58 chickens, E . coli was isolated from both the cellulitis and other lesions of colibacillosis, and 18.9% of the E . coli isolates from the 2 types of lesions belonged to the same O group . Escherichia coli of serogroups O78, O1, and O2 predominated . Isolates of the same serogroup that were derived from different lesions in the same birds had similar patterns of biotype, aerobactin production, serum sensitivity profile, antibiotic sensitivity, and