Cornea, 2004 Jan, 23(1), 76 - 80 Recurrent scleral abscess after uncomplicated cataract extraction; Goldstein MH et al.; PURPOSE: To report the unusual occurrence of a recurrent scleral abscess after uncomplicated cataract extraction . METHODS: Case report of a 77-year-old healthy woman . RESULTS: Multiple cultures and antibiotic treatments failed to resolve presenting symptoms . Gram stain, Gomori methenamine silver (GMS) stain, and all cultures were negative . After drainage of the abscess, the patient's symptoms cleared briefly, then returned 6 months later showing a positive GMS stain consistent with Candida . The patient was treated with amphotericin, natamycin, and fluconazole at this time, and a return in visual acuity occurred along with a resolution of symptoms . No re-occurrence has been noted with 2.5 years of follow-up . CONCLUSIONS: Cataract extraction, although generally a safe procedure, can still result in unusual complications such as scleral abscesses . Excellent outcomes are possible once the infections are identified and treated. Fam Pract, 2003 Dec, 20(6), 696 - 705 The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study; Hay AD et al.; BACKGROUND: Professional and parental uncertainty about the natural history of cough in pre-school children may in part be responsible for the high consultation and reconsultation rates and widespread antibiotic use in primary care . A recent systematic review of the natural history of cough included studies of unrepresentative, selected patients with heterogeneous measures and definitions of cough duration . OBJECTIVES: The aim of the present study was to describe the post-consultation duration of cough, compare this with clinician and parental prediction of cough duration, and to determine the clinical factors associated with prolonged cough . METHODS: A prospective cohort study of children aged 0-4 years with cough < or =28 days without asthma presenting to eight general practices in Leicestershire, UK was carried out . Socio-demographic and clinical data were collected, and parents and clinicians were asked to predict the proportion recovering within 7, 14, 21 and 28 days . Parents used a symptom diary to record cough and five other symptoms . Survival analysis was used to describe cough duration, and multivariable Cox regression was used to identify the factors independently associated with prolonged cough . RESULTS: Fifty percent of the children had recovered at 10 days and 90% at 25 days . Cough was associated with fever, breathlessness, disrupted sleep and reduced activity in a high proportion of children . Longer post-consultation cough was associated with longer pre-consultation cough and use of day care facilities . Clinicians overestimated how quickly children recovered from acute cough . Parents' predictions were accurate within 2 weeks, but they underestimated the proportion recovering in weeks 3 and 4 . CONCLUSIONS: Clinicians should be aware that from the parental perspective, acute cough is not a trivial illness and that some children remain unwell at 3-4 weeks . For health professionals negotiating the use of antibiotics, this information may enable parental self-care, reduce medicalization and displace the need to prescribe. J Biol Chem, 2004 Apr 16, 279(16), 15787 - 94 Epub 2003 Dec 30. Probing the role of metal ions in the catalysis of Helicobacter pylori 3-deoxy-D-manno-octulosonate-8-phosphate synthase using a transient kinetic analysis; Sau AK et al.; 3-Deoxy-d-manno-2-octulosonate-8-phosphate (KDO8P) synthase catalyzes the net condensation of phosphoenolpyruvate and d-arabinose 5-phosphate to form KDO8P and inorganic phosphate (Pi) . Two classes of KDO8P synthases have been identified . The Class I KDO8P synthases (e.g . Escherchia coli KDO8P synthase) catalyze the condensation reaction in a metal-independent fashion, whereas the Class II enzymes (e.g . Aquifex aeolicus) require metal ions for catalysis . Helicobacter pylori (H . pylori) KDO8P synthase, a Zn2+-dependent metalloenzyme, has recently been found to be a Class II enzyme and has a high degree of clinical significance since it is an attractive molecular target for the design of novel antibiotic therapy . Although the presence of a divalent metal ion in Class II KDO8P synthases is essential for catalysis, there is a paucity of mechanistic information on the role of the metal ions and functional differences as compared with Class I enzymes . Using H . pylori KDO8P synthase as a prototypical Class II enzyme, a steady-state and transient kinetic approach was undertaken to understand the role of the metal ion in catalysis and define the kinetic reaction pathway . Metal reconstitution experiments examining the reaction kinetics using Zn2+, Cd2+, Cu2+, Co2+, Mn2+, and Ni2+ yielded surprising results in that the Cd2+ enzyme has the greatest activity . Unlike Class-I KDO8P synthases, the Class II metallo-KDO8P synthases containing Zn2+, Cd2+, Cu2+, and Co2+ show cooperativity . This study presents the first detailed kinetic characterization of a metal-dependent Class II KDO8P synthase and offers mechanistic insight for how the divalent metal ions modulate catalysis through effects on chemistry as well as quaternary protein structure. Chem Biol, 2003 Dec, 10(12), 1215 - 24 Biosynthesis of deoxyamphotericins and deoxyamphoteronolides by engineered strains of Streptomyces nodosus; Byrne B et al.; Amphotericin B is an antifungal antibiotic produced by Streptomyces nodosus . During biosynthesis of amphotericin, the macrolactone core undergoes three modifications: oxidation of a methyl branch to a carboxyl group, mycosaminylation, and hydroxylation . Gene disruption was undertaken to block two of these modifications . Initial experiments targeted the amphDIII gene, which encodes a GDP-D-mannose 4,6-dehydratase involved in biosynthesis of mycosamine . Analysis of products by mass spectrometry and NMR indicated that the amphDIII mutant produced 8-deoxyamphoteronolides A and B . This suggests that glycosylation with mycosamine normally precedes C-8 hydroxylation and that formation of the exocyclic carboxyl group can occur prior to both these modifications . Inactivation of the amphL cytochrome P450 gene led to production of novel polyenes with masses appropriate for 8-deoxyamphotericins A and B . These compounds retained antifungal activity and may be useful new antibiotics. J Antibiot (Tokyo), 2003 Oct, 56(10), 827 - 31 Cyrmenins, new beta-methoxyacrylate inhibitors of the electron transport . Production, isolation, physico-chemical and biological properties; Sasse F et al.; New antibiotic compounds, named cyrmenins, were isolated from the culture broth of strains of the myxobacteria Cystobacter armeniaca and Archangium gephyra . The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are the first naturally occuring nitrogen-linked MOAs . The cyrmenins show nearly the same antifungal activity as strobilurin A, but are less toxic in a growth inhibition assay with L929 mouse cells . Cyrmenins inhibit NADH oxidation by submitochondrial particles from beef heart . Investigations by difference spectroscopy showed that cyrmenin B1 blocks the electron transport within the cytochrome bc1-segment (complex III) of the respiratory chain. Eur J Ophthalmol, 2003 Nov-Dec, 13(9-10), 798 - 9 Ocular complication of intralesional corticosteroid injection of a chalazion; Hosal BM et al.; PURPOSE: To report a major complication of intralesional corticosteroid injection for the treatment of a chalazion . METHODS: A 28-year-old woman presented with a 4-day history of decreased vision in her left eye that developed after corticosteroid injection to her upper eyelid for the treatment of chalazion . The visual acuity was 20/20 in her right and finger counting in her left eye . Anterior segment examination showed an inferior corneal opacity with positive Seidel test and cataract . RESULTS: A soft contact lens was applied to cornea and antibiotic therapy was given to prevent endophthalmitis . Cataract was removed by lens aspiration and a posterior chamber intraocular lens was implanted . After surgery, the visual acuity increased to 20/20 in her left eye . CONCLUSIONS: Inadvertent corneal penetration and traumatic cataract are possible and serious complications of intralesional corticosteroid injection. Rev Pneumol Clin, 2003 Sep, 59(4), 205 - 8 {A rare complication of chronic pancreatitis: pancreatico-pleural fistula}; Meybeck A et al.; Pleural effusion is a rare complication of chronic pancreatitis . We report a case observed in a 39-year-old patient hospitalized for dyspnea and pain in the lower left thorax . Chest x-ray revealed left pleural effusion . The exudative pleural fluid contained a very high amylase level . CT-scan revealed a pseudo-cyst of the tail of the pancreas extending into contact with the diaphragm and the chronic pancreatitis lesions . Medical treatment associating thoracic drainage, somatostatin analog, and antibiotics was unsuccessful . Thoracoscopic pleural decortication was performed . The patient then developed pneumonia involving the left base . A new antibiotic regimen was delivered and the pseudocyst was drained percutaneously under CT guidance . The clinical course was favorable at six months with partial involution of the pseudocyst and regression of the pulmonary images. Spine, 2004 Jan 1, 29(1), E7 - 9 Cervical epidural abscess after epidural steroid injection; Huang RC et al.; STUDY DESIGN: This is a case report of a cervical epidural abscess presenting with neurologic deficits after cervical epidural steroid injection . OBJECTIVE: To describe the presentation, diagnosis, treatment, and outcome of a rare complication of cervical epidural steroid injection . SUMMARY OF BACKGROUND DATA: Cervical epidural steroid injections are a commonly used modality in the treatment of cervical spine disease . Serious complications from the procedure are rare . There is only one previously reported case of cervical epidural abscess after cervical epidural injection in the literature . MATERIALS AND METHODS: A case of cervical epidural abscess after epidural steroid injection is presented and the relevant literature is reviewed . RESULTS: The patient had partial recovery of neurologic function within the first 24 hours after decompressive laminectomy, irrigation, and debridement . There were no perioperative complications . Intraoperative cultures permitted positive identification of the infecting organism and appropriate antibiotic selection . At 7-month follow-up, there was no recurrence of infection and the patient had recovered baseline neurologic function and neck pain status . CONCLUSIONS: Cervical epidural abscess is a rare but potentially devastating complication after epidural steroid injection . Neurologic compromise may occur . Timely diagnosis and appropriate treatment may result in good clinical outcomes. J Mol Biol, 2004 Jan 23, 335(4), 881 - 94 The translation initiation functions of IF2: targets for thiostrepton inhibition; Brandi L et al.; Bacterial translation initiation factor IF2 was localized on the ribosome by rRNA cleavage using free Cu(II):1,10-orthophenanthroline . The results indicated proximity of IF2 to helix 89, to the sarcin-ricin loop and to helices 43 and 44, which constitute the "L11/thiostrepton" stem-loops of 23S rRNA . These findings prompted an investigation of the L11 contribution to IF2 activity and a re-examination of the controversial issue of the effect on IF2 functions of thiostrepton, a peptide antibiotic known primarily as a powerful inhibitor of translocation . Ribosomes lacking L11 were found to have wild-type capacity to bind IF2 but a strongly reduced ability to elicit its GTPase activity . We found that thiostrepton caused a faster recycling of this factor on and off the 70S ribosomes and 50S subunits, which in turn resulted in an increased rate of the multiple turnover IF2-dependent GTPase . Although thiostrepton did not inhibit the P-site binding of fMet-tRNA, the A-site binding of the EF-Tu-GTP-Phe-tRNA or the activity of the ribosomal peptidyl transferase center (as measured by the formation of fMet-puromycin), it severely inhibited IF2-dependent initiation dipeptide formation . This inhibition can probably be traced back to a thiostrepton-induced distortion of the ribosomal-binding site of IF2, which leads to a non-productive interaction between the ribosome and the aminoacyl-tRNA substrates of the peptidyl transferase reaction . Overall, our data indicate that the translation initiation function of IF2 is as sensitive as the translocation function of EF-G to thiostrepton inhibition. Bioorg Med Chem Lett, 2004 Jan 19, 14(2), 373 - 6 Acetylene-based analogues of thiolactomycin, active against Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme; Senior SJ et al.; Analogues of the natural antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH condensing enzyme . In particular, 5-{3-(4-acetyl-phenyl)-prop-2-ynyl}-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited more than an 18-fold increased potency, compared to thiolactomycin, against this key condensing enzyme, involved in M . tuberculosis mycolic acid biosynthesis . Analogues of the antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded activity against cloned mtFabH condensing enzyme. Clin Immunol, 2003 Dec, 109(3), 272 - 7 An international study examining therapeutic options used in treatment of Wiskott-Aldrich syndrome; Conley ME et al.; Wiskott-Aldrich syndrome is a rare immunodeficiency characterized by thrombocytopenia, eczema, recurrent infections, autoimmunity, and an increased incidence of malignancy . Clinical severity is highly variable . As a first step toward the development of therapeutic guidelines, an international study to evaluate current treatment strategies was undertaken . A total of 73 centers from 24 countries participated . These centers provide care for 507 patients with Wiskott-Aldrich syndrome . Treatment strategies were strikingly variable in both small and large centers . Most options were used in at least some patients in the majority of centers, indicating that treatment is individualized; however, there were some clear trends . Most centers use intravenous gammaglobulin and prophylactic antibiotics in the majority of patients . Splenectomy was used more sparingly . Stem cell transplant was more likely to be used in centers providing care for 10 or more patients . Studies that better define prognostic markers and optimal therapy are needed. Med Clin (Barc), 2003 Dec 6, 121(20), 761 - 5 {Randomized, prospective and comparative clinical trial of piperacillin/tazobactam versus ceftriaxone plus ornidazole in the treatment of biliary tract infections}; Sirvent JM et al.; BACKGROUND AND OBJECTIVE: The treatment of biliary tract infections requires antibiotics and an appropriate surgical procedure . The aim of this study was to evaluate the efficacy and safety of piperacillin/tazobactam versus ceftriaxone plus ornidazole in the treatment of biliary tract infections . PATIENTS AND METHOD: This was a randomized, prospective and comparative clinical trial of two antibiotic regimens in the treatment of biliary tract infection . One hundred and fifty three patients were randomly allocated into two groups; three patients were excluded after randomization . One group (n = 75) received piperacillin/tazobactam (4 g/8 h iv) and the other group (n = 75) was administered a combination of ceftriaxone (2 g/24 h iv) plus ornidazole (1 g/24 h iv) . In both groups, protocolized surgical or endoscopic procedures were carried out . Clinical efficacy and safety were assessed at the end of treatment . RESULTS: Demographic data and severity of disease were similar in both groups . Three patients were excluded of the study by deviations from the protocol . Sixty-seven patients (89.3%) out of the piperacillin/tazobactam group and sixty-six patients (88%) out of the ceftriaxone plus ornidazole group were clinically cured (OR = 0.87 {95% CI, 0.31-2.4}) . Twelve patients died, seven in the piperacillin/tazobactam group and five in the ceftriaxone plus ornidazole group . Adverse events were similar in both groups (OR = 1.18 {95% CI, 0.37-3.7}) . CONCLUSIONS: This study suggests that piperacillin/tazobactam is as efficacious and safe as ceftriaxone plus ornidazole in the treatment of biliary tract infections. Am J Respir Crit Care Med, 2004 Jan 1, 169(1), 125 - 8 An indolent case of severe acute respiratory syndrome; Lam MF et al.; Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003 . Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels . We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia . She presented initially with fever and a normal chest radiograph . Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus . Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly . Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated. Cardiol Young, 2003 Oct, 13(5), 420 - 3 Recommendations for the use of palivizumab as prophylaxis against respiratory syncytial virus in infants with congenital cardiac disease; Tulloh R et al.; New data are emerging on the use of palivizumab as prophylaxis against infection with the respiratory syncytial virus in infants with congenital cardiac disease . Following a 4-year multicentre randomised trial, it was shown that prophylactic injections with palivizumab were effective and safe for such children . Prophylaxis consists of 5, monthly, intramuscular injections of palivizumab, at a dose of 15 mg/kg, given during the season for infection with the respiratory syncytial virus . Timing is at the discretion of the physician, depending on the onset of the season locally . It is suggested that, in the United Kingdom, this should be commenced in mid-September . To help clinicians to identify appropriate candidates for palivizumab, a working group of the British Paediatric Cardiac Association has developed recommendations . Infants, namely those under 1 year old, with congenital cardiac disease likely to benefit from prophylaxis include those with haemodynamically significant lesions, particularly increased pulmonary blood flow with or without cyanosis; pulmonary venous congestion, pulmonary hypertension or long-term pulmonary complications, residual haemodynamic abnormalities following medical or surgical intervention (patients who have undergone cardiopulmonary bypass should receive an injection as soon as they are medically stable), cardiomyopathy requiring treatment, and congenital cardiac disease likely to need hospital admission for medical or surgical intervention during the season of infection with the virus . Prophylaxis with palivizumab may also be indicated, at the discretion of the physician, in some children with complex cardiac disease over the age of 1 year . Children less likely to benefit from prophylaxis are those with haemodynamically insignificant disease, or those with lesions adequately corrected by medical or surgical intervention. Antimicrob Agents Chemother, 2004 Jan, 48(1), 319 - 22 FKS1 mutations responsible for selective resistance of Saccharomyces cerevisiae to the novel 1,3-beta-glucan synthase inhibitor arborcandin C; Ohyama T et al.; Arborcandin C is a novel antibiotic with potent antifungal activity that inhibits 1,3-beta-glucan synthase in fungi . We examined spontaneous Saccharomyces cerevisiae mutants which are selectively resistant to arborcandin C and revealed that a single amino acid replacement in Fks1p of Asn(470) with Lys or of Leu(642) with Ser confers selective resistance on Fks1p mutants. Anaesthesist, 2003 Dec, 52(12), 1124 - 31 {Anesthetic regimen for HIV positive parturients undergoing elective cesarean section}; Bremerich DH et al.; OBJECTIVE: Worldwide, 50 million people are infected with the human immunodeficiency virus (HIV), and 43% are women . Perinatal vertical transmission of HIV accounts for most new pediatric cases . Elective Cesarean delivery, combined antiretroviral therapy perioperatively and abandonment of breast-feeding postoperatively reduces vertical HIV transmission . However, the incidence of maternal and neonatal morbidity perioperatively is relatively unknown . The goal of the present study was to prospectively record perioperative maternal and neonatal complications in the largest HIV positive collective undergoing elective Cesarean section with spinal anesthesia published to date . METHODS: From 1999-2001, 54 HIV positive parturients were enrolled in this study . All parturients received IV zidovudine therapy (2 mg/kg body weight) perioperatively . Spinal anesthesia was performed using 60 mg of 4% hyperbaric mepivacaine plus 5 microg sufentanil intrathecally . Sensory, analgesic and motor block characteristics, the incidence of maternal hypotension, postoperative maternal complications as well as neonatal outcome were recorded . RESULTS: Short-term hypotension occurred in 65% of the parturients . Intraoperatively, one parturient died following amniotic fluid embolism . In 17% of the parturients, postoperative complications headed by wound healing impairment, bronchitis and pneumonia requiring prolonged antibiotic therapy were observed . To date, after a minimum observation period of 8 months, only one infant (1.8%) is HIV positive . CONCLUSION: Intrathecal mepivacaine combined with sufentanil in HIV positive parturients undergoing elective Cesarean section is an appropriate anesthetic option . Postoperative maternal morbidity was 17% . Neonatal outcome showed no evidence of neonatal depression. Tohoku J Exp Med, 2003 Dec, 201(4), 221 - 8 The effect of levamisole combined with the classical treatment in chronic brucellosis; Irmak H et al.; Levamisole is an immunopotenciator drug which is used as an antihelmintic drug as well as very effective remedy on cellular immunity compared with humoral immunity . A total 71 patients (37 men, 34 women) who referred to our department between March 1997 and December 2001, with a history of the disease for about 1 year, were diagnosed as having chronic brucellosis through those tests brucella serum agglutination test (SAT), SAT with Coombs and SAT with 2-mercaptoethanol . The patients were randomly divided into levamisole group (36 patients) and control group (35 patients) . All patients were given rifampicin 600 mg/day + doxycycline 200 mg/day for 6 weeks as a standard classical combined therapy for brucellosis . In the levamisole group, oral levamisole 80 mg every other day for 6 weeks was added to the treatment . There was a statistically significant difference between two groups, in complaints of arthralgia, fatigue and sweats before and 6 months after treatment, as well as in erythrocyte sedimentation rate and C-reactive protein elevations and lymphomonocytosis finding . While it was provided both clinical and serological improvement in all patients in the levamisole group; 11 patients in the control group did not improve both clinically and in view of specific and nonspecific laboratory findings and a recurrence occurred in one case, in this group . In conclusion, levamisole added to classical antibiotic therapy in treatment of chronic brucellosis was found quite efficient in all patients in providing adequate clinical and laboratory response in comparison to classical antibiotic therapy alone. J Biomed Mater Res B Appl Biomater, 2004 Jan 15, 68(1), 112 - 6 Influence of mixing method on the cement temperature-mixing time history and doughing time of three acrylic cements for vertebroplasty; Baroud G et al.; Acrylic cements are increasingly being used to augment osteoporotic vertebrae in a procedure called vertebroplasty . Two significant factors that may complicate the use of acrylic cements are: (a) short handling time, which may result in insufficient filling of the vertebra; and (b) exothermic setting (curing) behavior, which may result in thermal damage of the surrounding tissue . It has been previously reported that mixing the cement components under oscillation, as compared to manual mixing, increases the handling time . More specifically, it seems that oscillatory mixing slows down the cement polymerization process and, consequently, widens the time window during which cement is injectable . However, the effect of oscillatory mixing on the exothermic setting behavior of cement undergoing polymerization has not been examined . In this study, the exothermic setting behavior of three commercially available acrylic cements--Antibiotic Simplex, DP-Pour&trade, and Vertebroplastic--were examined for both manual and oscillatory mixing methods . For each combination of cement and mixing method, the parameters that were measured were the exothermic setting curve (and hence the cement setting temperature and setting time) and the cement doughing time . It was found that oscillatory mixing had no significant effect on any of these parameters . Based on the results of this study, it can be concluded that, for the tested cements, the setting process is a reaction-controlled process rather than a diffusion-controlled one . Clinically, this implies that oscillatory mixing may be used to increase the working period for acrylic cements without increasing the risk of thermal damage to surrounding tissue . J Biomed Mater Res B Appl Biomater, 2004 Jan 15, 68(1), 105 - 11 Influence of oscillatory mixing on the injectability of three acrylic and two calcium-phosphate bone cements for vertebroplasty; Baroud G et al.; Injecting acrylic and, increasingly, calcium-phosphate cements into the porous bone structure is an emerging procedure, referred to as vertebroplasty, for the augmentation of osteoporotic vertebrae . Despite the benefits of vertebroplasty, it has limitations . The limitations of interest in this study are the injectability of bone cements and their mixing variability (i.e., low reproducibility of resulting viscosity) . The objective of this study is to investigate the effect of oscillatory versus manual mixing on cement viscosity and mixing variability . Five cements are tested: (a) Vertebroplastic, (b) DP-Pour, (c) Antibiotic Simplex, (d) chronOS Inject, and (e) Biopex . Compared to manual mixing, oscillatory mixing significantly decreased the mean viscosity and the mixing variability, which was inferred from the coefficient of variation . For example, under oscillatory mixing, the viscosity and the variability for Vertebroplastic decreased to one-third of the corresponding values for manual mixing . Similar results were obtained for the other cements . The decrease in viscosity is attributed to the pseudo-plastic behavior of bone cements . The decrease in the variability of cement viscosity was attributed to greater dispersive mixing of the cement components under oscillatory mixing . The decrease in viscosity eases the injection by reducing the pressure required . The decrease in the variability of cement viscosity increases reproducibility of the cement injection . Oscillatory mixing appears to have the potential to contribute to improving vertebroplasty . J Pediatr (Rio J), 1994 Mar-Apr, 70(2), 113 - 4 {Ceftriaxione associated biliary lithiasis in newborns-report of two cases}; Rebello CM et al.; The occurrence of biliary calculosis as a complication of the use of ceftriaxone was first described in an 18-year-old patient with chronic granulomatosis . Since then many reports have been published on this type of complication both in children and in adults, but until the present moment, this complication had never been reported in pre-term neonates.The authors describe two cases of biliary calculosis associated with the use of ceftriaxone in preterm-newborns, emphasizing that due to the frequent use of this type of antibiotic in neonatal I.C.U., routine ultrasonographic control exams should be performed to diagnose this possible complication in all neonates receiving ceftriaxone. J Biochem (Tokyo), 2003 Nov, 134(5), 751 - 8 Negamycin restores dystrophin expression in skeletal and cardiac muscles of mdx mice; Arakawa M et al.; The ability of aminoglycoside antibiotics to promote read-through of nonsense mutations has attracted interest in these drugs as potential therapeutic agents in genetic diseases . However, the toxicity of aminoglycoside antibiotics may result in severe side effects during long-term treatment . In this paper, we report that negamycin, a dipeptide antibiotic, also restores dystrophin expression in skeletal and cardiac muscles of the mdx mouse, an animal model of Duchenne muscular dystrophy (DMD) with a nonsense mutation in the dystrophin gene, and in cultured mdx myotubes . Dystrophin expression was confirmed by immunohistochemistry and immunoblotting . We also compared the toxicity of negamycin and gentamicin, and found negamycin to be less toxic . Furthermore, we demonstrate that negamycin binds to a partial sequence of the eukaryotic rRNA-decoding A-site . We conclude that negamycin is a promising new therapeutic candidate for DMD and other genetic diseases caused by nonsense mutations. Infect Immun, 2004 Jan, 72(1), 440 - 50 Brucella abortus rough mutants are cytopathic for macrophages in culture; Pei J et al.; Rough mutants of Brucella spp . are attenuated for survival in animal models . However, conflicting in vitro evidence has been obtained concerning the intracellular survival of rough mutants . Transposon-derived rough mutants isolated in our laboratory were previously shown to exhibit small but significant reductions in intracellular survival in a 12-h in vitro assay . Several recent publications report that rough mutants exhibited increased macrophage uptake relative to their smooth parental strains, and a reduction in numbers at the end of the assay has been interpreted as intracellular killing . In an effort to explore the role of O antigen in the interaction between Brucella abortus and macrophages, we have monitored the uptake of rough mutants and survival in vitro by using the murine macrophage cell line J774.A1 . The results confirm a 10- to 20-fold-increased uptake of rough mutants over that of smooth organisms under standard conditions . Recovery of the rough mutants persisted up to 8 h postinfection, but at the point when intracellular replication of the smooth organisms was observed, the number of rough organisms recovered declined . Fluorescence microscopy revealed the intracellular multiplication of both smooth and rough organisms, and assays performed in the absence of antibiotic confirmed the replication of the rough organisms . Examination by phase-contrast microscopy revealed the lytic death of macrophages infected with the rough mutants, which was confirmed by the release of lactate dehydrogenase (LDH) from the cell cytoplasm . Thus, the decline in the number of rough organisms was the result of the lysis of macrophages and not from intracellular killing . The cytopathic effect is characterized as necrotic rather than apoptotic cell death based on early LDH release, annexin V and propidium iodide staining, morphological changes of infected cells and nuclei, and glycine protection . The cytopathic effect was observed with macrophages at multiplicities of infection (MOIs) of as low as 20 and was not observed with epithelial cells at MOIs of as high as 2000 . These findings suggest a role for O antigen during the early stages of host-agent interaction that is essential in establishing an intracellular niche that maintains and supports persistent intracellular infection resulting in disease. J Antimicrob Chemother, 2004 Feb, 53(2), 133 - 6 Epub 2003 Dec 19. A new millennium conundrum: how to use a powerful class of influenza anti-neuraminidase drugs (NAIs) in the community; Oxford J et al.; Influenza A and B viruses cause serious medical problems and social disruption every year in particular countries of the world . The virus is notoriously fickle and may attack citizens in say two adjacent countries but not the third . More rarely a global pandemic virus emerges causing millions of deaths worldwide . The SARS outbreak has illuminated weaknesses in planning for sudden outbreaks of disease in a modern society and in particular how panic can grip and cause intense economic disruption . Many communities in the world are neither prepared for a global pandemic nor a very acute epidemic of influenza . The neuraminidase inhibitors (NAIs) are a new class of antiviral drug targeting a viral influenza enzyme, the neuraminidase, which acts both to facilitate virus infection of cells by clearing a passage through otherwise protective respiratory fluids and also by helping release of the virus by cutting the chemical umbilical cord which links up the virus to the infected cell . Extensive laboratory studies of the two molecules zanamivir and oseltamivir have shown that they block all influenza A and B viruses yet tested and would, in theory, even inhibit the 1918 pandemic virus . Both drugs can be used prophylactically to prevent spread of infection in families and communities where 80-90% protection has been documented . The therapeutic effects are also strong in adults and children abbreviating infection, reducing quantities of excreted virus and reducing antibiotic prescriptions . The drugs have to be taken within 48 h of the onset of symptoms . Drug resistance is not a problem at present because although such mutants occur the mutants are compromised and are less virulent than their drug-sensitive parents and they spread less easily . The two drugs could be stockpiled to prepare for an influenza pandemic but, importantly, clinical and scientific experience need to be gained by using these inhibitors in the yearly conflagrations of epidemic influenza, which unchecked do great harm to our communities. Curr Med Res Opin, 2003, 19(8), 753 - 9 Comparison of lenograstim and filgrastim on haematological effects after autologous peripheral blood stem cell transplantation with high-dose chemotherapy; Kim IH et al.; OBJECTIVE: To compare the efficacy of lenograstim and filgrastim on haematological recovery following an autologous peripheral blood stem cell transplantation (PBSCT) with high-dose chemotherapy . METHODS: A retrospective case-controlled study . RESULTS: Absolute neutrophil count (ANC) recovery above 0.5 x 10(9)/l and white blood cell (WBC) recovery above 4 x 10(9)/l for 3 consecutive days was achieved earlier with filgrastim than with lenograstim ((13.2 +/- 8.0 vs 19.0 +/- 10.0 days, p = 0.004), (16.9 +/- 9.7 vs 29.9 +/- 16.6 days, p = 0.001), respectively) . The platelet recovery above 20 x 10(9)/l was also achieved earlier with filgrastim than with lenograstim (19.5 +/- 11.6 vs 27.2 +/- 13.8 days, p = 0.006) . Furthermore, filgrastim-treated patients received fewer days of granulocyte colony simulating factor (G-CSF) administration (12.5 +/- 7.0 vs 18.6 +/- 8.5 days, p = 0.001) and spent less time in hospital (23.7 +/- 10.9 vs 32.0 +/- 17.6 days, p = 0.009) . Duration of antibiotic administration was also significantly shorter in the filgrastim group (13.6 +/- 7.6 vs 29.1 +/- 19.8 days, p = 0.001) . CONCLUSION: In patients undergoing PBSCT following high-dose chemotherapy, filgrastim significantly reduced the duration of neutropenia, thrombocytopenia and days of G-CSF administration, and led to earlier hospital discharge compared with lenograstim. Differentiation, 2003 Dec, 71(9-10), 578 - 85 Limb bud progenitor cells induce differentiation of pluripotent embryonic stem cells into chondrogenic lineage; Sui Y et al.; Pluripotent embryonic stem (ES) cells are the most versatile cells, with the potential to differentiate into all types of cells . However, the cellular and molecular mechanisms responsible for their differentiation into specific lineages have not been elucidated . Recent studies in human ES cells have challenged the scientific community to focus research on the basic mechanisms of stem cell differentiation for their potential applications in regenerative medicine and cell-based therapies . The majority of studies thus far have focused on cells that are already committed to specific lineages . The current studies were designed to establish a system for investigating the mechanisms of cell fate determination starting from undifferentiated ES cells, to gain insight into events during the normally inaccessible period of development . Here we demonstrate that pluripotent ES cells can be programmed to differentiate into chondrocytes, the cartilage-producing cells, by co-culture with progenitor cells from the limb buds of the developing embryo . Almost 60%-80% of the cells exhibited phenotypic characteristics of mature chondrocytes and expressed genes such as sox9, collagen type II, and proteoglycans, which was accompanied by a decrease in ES cell-specific transcription factor Oct-4 . Collagen type II, which is expressed in two different forms during chondrogenic differentiation due to the alternate splicing of mRNA, was also properly regulated . The studies presented here suggest that the signals produced by progenitor cells from the developing embryo can induce lineage-specific differentiation . The system described here may serve as an in vitro model to study the mechanisms of cell fate determination by stem cells. J Endod, 2003 Dec, 29(12), 841 - 3 Extraoral sinus tract misdiagnosed as an endodontic lesion; Cohenca N et al.; The extraoral sinus tract may occur as a result of an inflammatory process associated with a necrotic pulp . However, several non-odontogenic disorders may also produce an extraoral sinus tract . Thus, the differential diagnosis of this clinical finding is of paramount importance in providing appropriate clinical care because misdiagnosis of this condition may result in healing failure or unnecessary treatment . This case report of a 19-yr-old male patient describes an extraoral cutaneous sinus tract misdiagnosed as an endodontic lesion . Consequently, the patient underwent unnecessary exploratory procedures and antibiotic therapy . Identification of the inflammatory source of the lesion and removal of the affected tissue led to tissue healing. Int J Clin Pract, 2003 Nov, 57(9), 775 - 7 Persistent otorrhoea after ventilation tube insertion: a treatment protocol; Siddiq MA et al.; Otorrhoea is the commonest complication of ventilation tube (grommet) insertion . In some cases it may be unresponsive to short courses of topical antibiotic/steroid drops and/or systemic antibiotics . This study investigated whether a five-day course of inpatient treatment with intravenous antibiotics, topical medication and daily microsuction was effective in treating persistent otorrhoea . Eleven subjects were included, of whom nine responded to the proposed treatment regimen . We recommend that patients with persistent otorrhoea after ventilation tube insertion should be managed according to these guidelines before considering an examination under anaesthetic or a ventilation tube removal. Am J Health Syst Pharm, 2003 Dec 1, 60(23 Suppl 8), S17 - 21 Formulary considerations for drugs used to prevent cytomegalovirus disease; Pescovitz MD; Four types of therapeutic strategies for managing cytomegalovirus (CMV) in solid organ transplant recipients, the mechanisms of action and efficacy of drugs used for prophylaxis, and the criteria for evaluating drugs for inclusion in a formulary are described . Universal and selective prophylaxis are simple to implement and effective for CMV prophylaxis, but they are costly and patient nonadherence and viral resistance can develop . Preemptive therapy may cause less resistance and cost less, but it is more complex and associated with a higher incidence of infection, which may have no effect on secondary effects from CMV infection, and higher recurrence of disease than prophylactic therapy . Treatment of active disease may be less costly for the drug than other approaches, but intravenous access is required and the rates of infection recurrence and mortality are higher compared with prophylaxis and preemptive therapy . Criteria for deciding which CMV prophylactic drugs to include in a formulary include efficacy, safety, convenience, and cost . CMV immune globulin i.v . is costly and exhibits reduced efficacy when used alone in patients at high risk for CMV disease . Intravenous ganciclovir is effective, but it is costly because of infusion costs . Intravenous drug therapies are inconvenient and associated with a risk of bacterial and fungal infection . Oral acyclovir is safe to use and inexpensive (since a genetic exists), but it has poor efficacy and is inconvenient because of the need for four large daily doses . Valacyclovir is more convenient and with similar safety and probably better efficacy than acyclovir, but it is more costly . Oral ganciclovir and oral valganciclovir have similar safety and costs, with greater efficacy than acyclovir . The single daily dose and lack of resistance to valganciclovir are advantages over oral ganciclovir, which requires three daily doses and can result in the development of resistance. Am J Health Syst Pharm, 2003 Dec 1, 60(23 Suppl 8), S13 - 6 New prophylactic treatment strategy for cytomegalovirus disease; Lake KD; The pharmacology, pharmacokinetics, safety, and efficacy of valganciclovir, an oral prodrug for ganciclovir, used to prevent cytomegalovirus (CMV) disease in solid organ transplant recipients are described . Valganciclovir was developed to overcome the disadvantages associated with ganciclovir, which include low oral bioavailability, limited efficacy because of the development of viral resistance, and the need for frequent administration, which can adversely affect patient adherence . Valganciclovir is rapidly converted to ganciclovir; systemic exposure to the parent drug is low and short in duration . The oral bioavailability of ganciclovir from valganciclovir is 10 times higher than that from the original ganciclovir formulation . Food increases the oral bioavailability of valganciclovir . In a four-way, randomized, crossover pharmacokinetic study of 28 liver transplant recipients, single doses of valganciclovir 900 mg and intravenous ganciclovir 5 mg/kg resulted in a similar ganciclovir systemic exposure . The systemic exposure was proportionately lower with a single 450-mg dose of valganciclovir but similar to that of oral ganciclovir 3 g administered in three divided doses . In the recent multicenter, randomized, double-blind, double-dummy PV16000 trial in 364 solid organ transplant recipients at high risk for CMV disease (i.e., CMV-negative recipients of CMV-positive donor organs), valganciclovir 900 mg once daily was as effective in preventing CMV-disease as oral ganciclovir 1 g three times daily . Resistance was reported with ganciclovir but not with valganciclovir . Both drugs were well tolerated. Am J Health Syst Pharm, 2003 Dec 1, 60(23 Suppl 8), S9 - 12 Cost advantages of oral drug therapy for managing cytomegalovirus disease; Somerville KT; Cost advantages of the oral route of drug therapy administration over the intravenous route for managing cytomegalovirus (CMV) disease are described . The overall costs usually are lower for the oral route of administration than for the intravenous route, although the cost to the patient depends on insurance coverage . Other advantages of the oral route include greater safety and convenience, which may improve patient adherence and quality of life . In patients with acquired immunodeficiency syndrome (AIDS), the use of oral ganciclovir instead of intravenous ganciclovir to treat the maintenance phase of CMV retinitis reduced the incidence of neutropenia and sepsis, outpatient and inpatient resource use, and costs . Oral therapy also improved patient quality of life . A cost-effectiveness model for liver transplant recipients found that CMV prophylaxis is warranted for all patients, ganciclovir is preferred over CMV immune globulin i.v . and oral acyclovir for prophylaxis, and the oral route of administration is more cost-effective than the intravenous route for ganciclovir . Valganciclovir, the oral prodrug of ganciclovir, was not included in this model . Oral maintenance therapy is usually cost-effective, safer, and more convenient than intravenous therapy in the management of CMV. Am J Health Syst Pharm, 2003 Dec 1, 60(23 Suppl 8), S5 - 8 Costs and consequences of cytomegalovirus disease; Schnitzler MA; The impact of prophylactic oral ganciclovir therapy on the incidence of cytomegalovirus (CMV) disease, patient and graft survival, and costs in patients receiving kidney and liver transplants is described . CMV disease is a common cause of morbidity and mortality in solid organ transplant recipients unless prophylactic drug therapy is used . Prophylactic oral ganciclovir therapy reduces the incidence of CMV disease in kidney and liver transplant recipients . It is more effective for recipients who are seronegative before the transplant and receive organs from seronegative (D-/R-) donors than in seronegative recipients of organs from seropositive (D+/R-) donors . CMV disease remains a problem in the latter . CMV disease increases the risk of graft failure, which decreases the likelihood of patient survival . The extent of matching of the DR subregion of the human leukocyte antigen complex in the donor and recipient may affect graft survival in patients with CMV disease . Graft failure is costly and should be considered in economic analyses of CMV prophylaxis regimens because of the potential impact of prophylaxis on CMV disease . The use of oral ganciclovir for CMV prophylaxis has reduced the incidence of CMV disease in kidney and liver transplant recipients. Indian J Malariol, 2002 Mar-Jun, 39(1-2), 26 - 33 Enhancement of antimalarial activity of chloramphenicol against Indian Plasmodium falciparum isolates in vitro by chloroquine; Biswas S; The antimalarial activity of chloramphenicol, a broad-spectrum antibiotic was studied in three Indian Plasmodium falciparum isolates having high or low sensitivity to chloroquine . The antimalarial activity was evaluated in 72 hours culture in the presence of various doses of chloramphenicol alone or in combination with a fixed dose of chloroquine added at a concentration that is well tolerated by parasites in vitro . Significant growth inhibition with chloramphenicol was observed at concentrations above 10 micrograms/ml in three isolates . However, an increase in the antimalarial activity of the compound at low concentrations in the range of 0.25-2.5 micrograms/ml has also been observed in the presence of chloroquine . Parasite growth was significantly inhibited in chloroquine resistant parasites . Use of chloramphenicol with chloroquine may be useful as a combination therapy to improve efficacy of the antimalarials and to retard the development of resistance to the individual components of the combination. Arch Gynecol Obstet . 2003 Dec 19; {Epub ahead of print} Granulomatous mastitis; Diesing D et al.; INTRODUCTION . Granulomatous mastitis (GM) is a rare disease which predominantly occurs in premenopausal women shortly after their last childbirth . ETIOLOGY . Its etiology is unclear, however, the disease has been shown to be correlated with breast-feeding and the use of oral contraceptives . An autoimmune component has also been discussed . PRESENTATION . It presents with the clinical symptoms of galactorrhea, inflammation, breast mass, tumorous indurations and ulcerations of the skin . In mammography and sonography nodular opacities and hypoechoic nodules are found . Very often clinical and radiological findings mimic breast cancer . HISTOLOGICAL DIAGNOSIS . The diagnosis is made by histopathology . Histological features in GM include signs of a chronic granulomatous inflammation with giant cells, leucocytes, epitheloid cells and macrophages as well as abscesses . TREATMENT . Therapy of GM consists of complete surgical excision combined with oral steroid therapy, eventually in combination with anti-inflammatory drugs or colchicine . Use of methotrexate has also been successful . In case of formation of abscesses antibiotic therapy should be applied before steroid therapy . Immune-suppressive therapy should be performed until complete remission as rates of recurrence can be up to 50%. Rev Port Pneumol, 2003 Mar-Apr, 9(2), 161 - 72 {Lung abscess in infancy--a rare disease . Clinical cases}; Machado MA et al.; Lung abscess is a rare entity in childhood, but leads to high morbidity and long length of hospitalisation . It appears commonly in children with risk factors or other disease, have a good response to antibiotic therapy and it is rarely necessary the use of invasive techniques . Authors present two cases of lung abscess in children, one of them with risk factors to aspiration, that improved with antibiotic therapy and make a revision about this entity in infancy. J Pediatr (Rio J), 1999 Jan-Feb, 75(1), 29 - 33 {Plasmatic levels of interleukin-1beta and interleukin-6 in newborn infants with fever}; Silveira RC et al.; OBJECTIVE: To study plasma levels of IL-1beta and IL-6 in order to distinguish the presence of bacterial infection in newborn infants with fever . METHODS: A cohort of 117 newborn infants with postnatal age equal to or less than 5 days, with no previous use of antibiotic therapy, and with clinical suspicion of bacterial infection was studied from July 1995 through August 1996 . Those with definite criteria for sepsis were considered infected . Fever was defined as axillar temperature > 37.5 degrees C in three independent measurements . The patients were classified in four different groups: Group 1: infected with fever; Group 2: infected without fever; Group 3: not infected with fever; Group 4: not infected without fever . Complete blood count, platelet count, blood or other fluid cultures, and plasmatic levels of IL-1beta and IL-6 were collected before the beginning of antibiotic therapy . RESULTS: Of the 117 newborn infants studied were 66 infected and 51 not infected . Fever was present in 45 (38.46%) . The median values of IL-1beta and IL-6 were significantly higher in newborn infants with fever than in those with no fever . There were significant differences between groups 1 and 2, 1 and 4, and 2 and 3 for IL-1beta . There were no significant differences between groups 2 and 4, and 1 and 3 for IL-1beta . Eight (72%) newborn infants with no infection and no fever had environment heating, and 3 had dehydration . There were no differences in median IL-6 levels between groups 1 and 2, and 3 and 4 . There were significant differences in the median IL-6 levels between groups 1 and 3, and 1 and 4 . CONCLUSIONS: IL- 6 is a marker of early neonatal sepsis . IL-1beta is related to neonatal fever response independently of the presence of bacterial infection. J Pediatr (Rio J), 1997 Jul-Aug, 73(4), 269 - 72 {Lateral sinus thrombophlebitis and cervical abscess as a complication of chronic otitis media}; Saffer M et al.; OBJECTIVE: To focus on two rare complications of cholesteatomatous chronic otitis media.METHODS: A case of two simultaneous complications of cholesteatoma (lateral sinus thrombophlebitis and Bezold's cervical abscess) in a 7 year-old boy is reported . Thereafter, a review of the international literature about both complications is carried out . RESULTS: A 7 year-old white male patient was referred for assessment with high fever, obnubilation, cervical mass and otorrhea, being non-responsive to the clinic treatment, with the diagnostic hypothesis of infectious parotitis.The clinical examination and radiologic study demonstrated lateral sinus thrombophlebitis and cervical abscess due to cholesteatoma in the right ear . After being submitted to surgery and prolonged intravenous antibiotic therapy, the patient presented a favorable outcome, with little morbidity . CONCLUSION: Despite the incidence of complications of otitis had decreased in the last decades, they are still a challenge for the clinician, especially because of the insidious manner of presentation, usually hidden with the indiscriminate use of antibiotics. J Pediatr (Rio J), 19atric Nursery of the Hospital das Clinicas of the Medical School of the Campinas State University (UNICAMP).METHODS: The data of the patients with diagnosis of brain abscess recorded between January 1986 and July 1995 were reviewed . The following data were analyzed: age, sex, clinical manifestations, physical examination, radiological data, etiological agent, treatment, complications and clinical evolution of the patients.RESULTS: The age of the patients varied from 2 to 13 years (median 3 years); 6 of them were female . The neurological manifestations predominated, and 2 patients had history of prior otorhinolaryngological infection (chronic otitis media and sinusitis) . Two patients had congenital cyanogenic cardiopathy (Fallot tetralogy and Pulmonary Stenosis with Interventricular Communication) . The diagnosis and follow-up were made with computed tomography of the brain . In six cases there were one sole abscess located more frequently in the frontal lobe . The treatment in majority of the cases was broad-spectrum antibiotic association and surgical drainage . Five patients had neurological sequelae (seizure, hydrocephalus and paresis); one death occurred.CONCLUSIONS: Although rare, the brain abscess has to be remembered in patients that have neurological alterations associated to risk factors, as otorhinolaryngological infections and congenital cyanotic cardiopathy, being mandatory the realization of computed tomography of the brain to confirm the diagnosis. Org Biomol Chem, 2003 Dec 7, 1(23), 4227 - 34 Epub 2003 Oct 29. Synthesis of regioisomeric analogues of crisamicin A; Brimble MA et al.; The synthesis of bis-furonaphthopyrans 12a and 12b, regioisomeric analogues of the dimeric pyranonaphthoquinone antibiotic crisamicin A 1 is described . The key intermediate 16 was prepared via a oatric Nursery of the Hospital das Clinicas of the Medical School of the Campinas State University (UNICAMP).METHODS: The data of the patients with diagnosis of brain abscess recorded between January 1986 and July 1995 were reviewed . The following data were analyzed: age, sex, clinical manifestations, physical examination, radiological data, etiological agent, treatment, complications and clinical evolution of the patients.RESULTS: The age of the patients varied from 2 to 13 years (median 3 years); 6 of them were female . The neurological manifestations predominated, and 2 patients had history of prior otorhinolaryngological infection (chronic otitis media and sinusitis) . Two patients had congenital cyanogenic cardiopathy (Fallot tetralogy and Pulmonary Stenosis with Interventricular Communication) . The diagnosis and follow-up were made with computed tomography of the brain . In six cases there were one sole abscess located more frequently in the frontal lobe . The treatment in majority of the cases was broad-spectrum antibiotic association and surgical drainage . Five patients had neurological sequelae (seizure, hydrocephalus and paresis); one death occurred.CONCLUSIONS: Although rare, the brain abscess has to be remembered in patients that have neurological alterations associated to risk factors, as otorhinolaryngological infections and congenital cyanotic cardiopathy, being mandatory the realization of computed tomography of the brain to confirm the diagnosis. Org Biomol Chem, 2003 Dec 7, 1(23), 4227 - 34 Epub 2003 Oct 29. Synthesis of regioisomeric analogues of crisamicin A; Brimble MA et al.; The synthesis of bis-furonaphthopyrans 12a and 12b, regioisomeric analogues of the dimeric pyranonaphthoquinone antibiotic crisamicin A 1 is described . The key intermediate 16 was prepared via a one-pot in situ Suzuki-Miyaura homocoupling of naphthyl triflate 23 using bis(pinacolato)diboron . Oxidation of binaphthyl 16 to bis-naphthoquinone 14 was then effected with silver(II) oxide and nitric acid . Efficient double furofuran annulation of bis-naphthoquinone 14 with 2-trimethylsilyloxyfuran 8 afforded bis-furonaphthofuran adducts 13a and 13b as an inseparable 1:1 mixture of diastereomers . Oxidative rearrangement of this mixture of bis-furonaphthofuran adducts 13a and 13b using silver(II) oxide and nitric acid afforded unstable bis-furonaphthopyrans 12a and 12b also as a 1:1 mixture of diastereomers . Addition of 2-trimethylsilyloxyfuran 8 to naphthoquinone 25 afforded adduct 26 that underwent oxidative rearrangement to furonaphthopyran 27, however attempts to effect Suzuki-Miyaura homocoupling of triflates 26 and 27 to their respective dimers 13 and 12, was unsuccessful. J Periodontol, 2003 Nov, 74(11), 1696 - 704 Position paper: periodontal diseases of children and adolescents; Califano JV; Research et al.; Children and adolescents are subject to several periodontal diseases . Although there is a much lower prevalence of destructive periodontal diseases in children than in adults, children can develop severe forms of periodontitis . In some cases, this destructive disease is a manifestation of a known underlying systemic disease . In other young patients, the underlying cause for increased susceptibility and early onset of disease is unknown . These diseases are often familial, suggesting a genetic predisposition for aggressive disease . Current modalities for managing periodontal diseases of children and adolescents may include antibiotic therapy in combination with non-surgical and/or surgical therapy . Since early diagnosis ensures the greatest chance for successful treatment, it is important that children receive a periodontal examination as part of their routine dental visits. J Vasc Surg, 2003 Dec, 38(6), 1199 - 205 Intra-abdominal aortic graft infection: complete or partial graft preservation in patients at very high risk; Calligaro KD et al.; BACKGROUND: Total graft excision with in situ or extra-anatomic revascularization is considered mandatory to treat infection involving the body of aortic grafts . We present a series of nine patients with this complication and such severe comorbid medical illnesses or markedly hostile abdomens that traditional treatments were precluded . In these patients selective complete or partial graft preservation was used . METHODS: Over the past 20 years we have treated nine infected infrarenal aortic prosthetic grafts with complete or partial graft preservation, because excision of the graft body was not feasible . In all nine patients infection of the main body of the aortic graft was documented at computed tomography or surgery . Essential adjuncts included percutaneous or operative drain placement into retroperitoneal abscess cavities and along the graft, with instillation of antibiotics three times daily, repeated debridement of infected groin wounds, and intravenous antibiotic therapy for at least 6 weeks . RESULTS: One patient with purulent groin drainage treated with complete graft preservation died of sepsis . One patient with groin infection treated with complete graft preservation initially did well, but ultimately required total graft excision 5 months later, after clinical improvement . In four patients complete graft preservation was successful; two patients required excision of an occluded infected limb of the graft; and one patient underwent subtotal graft excision, leaving a graft remnant on the aorta, and axillopopliteal bypass . In summary, seven of nine patients survived hospitalization after complete or partial graft preservation; amputation was avoided in all but one patient; and no recurrent infection developed over mean follow-up of 7.6 years (range, 2-15 years) . CONCLUSIONS: Although contrary to conventional concepts, partial or complete graft preservation combined with aggressive drainage and groin wound debridement is an acceptable option for treatment of infection involving an entire aortic graft in selected patients with prohibitive risks for total graft excision . This treatment may be compatible with long-term survival and protracted absence of signs or symptoms of infection. RNA, 2004 Jan, 10(1), 90 - 101 Purine bases at position 37 of tRNA stabilize codon-anticodon interaction in the ribosomal A site by stacking and Mg2+-dependent interactions; Konevega AL et al.; The anticodon loop of tRNA contains a number of conserved or semiconserved nucleotides . In most tRNAs, a highly modified purine is found at position 37 immediately 3' to the anticodon . Here, we examined the role of the base at position 37 for tRNA(Phe) binding to the A site of Escherichia coli ribosomes . Affinities and rate constants of A-site binding of native yeast peptidyl-tRNA(Phe) with hypermodified G (wybutine), or of unmodified peptidyl-tRNA(Phe) transcripts with G, A, C, or U, at position 37 were measured . The data indicate that purines stabilize binding due to stronger stacking and additional interactions with the ribosome mediated by Mg(2+) ions . Paromomycin, an antibiotic that binds to 16S rRNA in the decoding center, greatly stabilized tRNAs in the A site and abolished the Mg(2+)-dependence of binding . Comparison of binding enthalpies and entropies suggests that hypermodification of the base at position 37 does not affect stacking in the codon-anticodon complex, but rather decreases the entropic penalty for A-site binding . Substitution of purines with pyrimidines at position 37 increases the rates of tRNA binding to and dissociation from the A site . The data suggest that initial binding of tRNA to the A site is followed by a rate-limiting rearrangement of the anticodon loop or the ribosome decoding center that is favored by purines at position 37 and involves stronger stacking, additional Mg(2+) binding, and interactions with 16S rRNA. Nucleic Acids Res, 2004 Jan 1, 32 Database issue, D593 - 4 The Peptaibol Database: a database for sequences and structures of naturally occurring peptaibols; Whitmore L et al.; The Peptaibol Database is a sequence and structure resource for the unusual class of peptides known as peptaibols . These peptides exhibit antibiotic and membrane channel-forming activities . The database includes sequence, biological source and bibliographical data for the naturally occurring peptaibols . Information is also collated for the growing number of peptaibol 3D structures determined by either crystallography or NMR spectroscopy . The database can be obtained as a whole or can be queried by name, group, sequence motif, biological origin and/or literature reference . The Peptaibol Database can be freely accessed at http://www.cryst.bbk.ac.uk/peptaibol. Eur Respir J, 2003 Dec, 22(6), 956 - 61 Can early infection explain the sibling effect in adult atopy? Cullinan P, Harris JM, Newman Taylor AJ, Jones M, Taylor P, Dave JR, Mills P, Moffat SA, White CW, Figg JK, Moon AM, Barnes MC. Atopy is strongly and inversely related to family size, a pattern which is plausibly assumed to reflect a protective effect of early infection . The current study tested this hypothesis by case-referent analysis of an adult cohort in the UK . The study established that atopy, defined by prick tests to common aeroallergens, was less common among those from larger families after adjustment for potentially confounding factors . In particular, a higher number of brothers appeared to offer protection . The current authors attempted to explain this distribution by examining contemporary family-doctor records of early childhood infections; and by a number of other indirect indices of early-life "hygiene" . The sibling effect was unexplained by evidence of infection with either hepatitis A or Helicobacter pylori, or by counts of infections or antibiotic prescriptions in early life . There was a significant and independent negative association between the number of gastrointestinal infections before the age of 5 yrs and the odds of atopy . Dog ownership and home moving in early life also displayed potentially protective associations . Although the current study replicates the finding that atopy is inversely associated with family size this could not be explained by documentary or serological evidence of early infection . The findings support the suggestion that the "sibling effect" in atopy may not simply reflect protection by early infection. Therapie, 2003 Jul-Aug, 58(4), 361 - 6 {Adverse cardiovascular and central neurologic reactions to sympathomimetics used as nasal decongestants: results of the French National Pharmacovigilance Survey}; Olivier P et al.; Remedies for coughs and colds often contain both an indirect sympathomimetic agent plus another drug (anti-inflammatory, analgesic or antibiotic, etc.) . In France, oral sympathomimetics are available over the counter, and preparations for topical use (nasal sprays or drops) require a medical prescription . Using the French Pharmacovigilance database, we performed a retrospective study to identify cardiovascular and neurological adverse drug reactions (ADRs) associated with the use of nasal decongestants containing a sympathomimetic agent . Of a total of 165 ADRs . 15 were strokes or cerebral haemorrhages . We also found the following: 67 cases of arterial hypertension, 33 of convulsions, 28 of headaches and 24 of vasomotor symptoms involving the extremities . In most of these cases, misuse or a predisposing factor was found (such as a history of arterial hypertension or headache, the combination of two decongestants, long-term use, etc.) . The incidence of cardiovascular or neurological ADRs with cold remedies seems 'very rare' but some of these reactions, mainly stroke, are 'serious' . However, there is no available clinical evidence showing the benefit of such agents after repeated use over several days . Since most of the nasal decongestants are freely available without prescription, drug information is needed to advise prescribers and also patients about risk of 'serious' ADRs with these drugs. J Eur Acad Dermatol Venereol, 2004 Jan, 18(1), 69 - 72 Mast cells and IgE-containing cells in gastric mucosa of Helicobacter pylori infected and non-infected patients with chronic urticaria; Liutu M et al.; BACKGROUND: Several studies have indicated that antibiotic therapy aimed at eradication of Helicobacter pylori has effects on symptoms of chronic urticaria (CU) patients . However, the possible connections and pathomechanism by which H . pylori might be linked to CU have remained largely unknown . The IgE-mediated pathway might be a possible link between H . pylori infection and CU . We therefore clarified the role of H . pylori as an inducer of IgE response . MATERIALS AND METHODS: Gastroscopy was performed and mucosal biopsy specimens were taken to evaluate the histology, as well as the presence of H . pylori bacteria, mast cells and IgE-containing cells in the antral mucosa, in 21 CU patients . Controls (n = 48) included 19 patients with lichen planus, nine patients with atopic dermatitis and 20 patients with no skin or allergic disease . RESULTS: The mean densities of IgE-containing cells were significantly higher in H . pylori-infected patients and in patients with skin disease compared to non-H . pylori-infected patients with no skin or allergic disease . No significant difference was found in the number of IgE-containing cells between H . pylori-infected and non-infected patients with CU . There was no significant difference in the mean densities of mast cells in the different patient groups . CONCLUSIONS: Our findings suggest that H . pylori gastritis leads to increased IgE production . However, we could not show a significant difference in IgE staining between H . pylori-infected and non-infected patients with CU. Bone Marrow Transplant, 2004 Feb, 33(3), 347 - 50 Efficacy and safety of femoral vascular access for peripheral blood stem cell (PBSC) collection; Moreiras-Plaza M et al.; Central venous catheters are frequently used in leukapheresis to provide high flow rates . The most common locations are the subclavian or jugular vein, but insertion-related complications and inadequate flow are frequent problems . Experience using femoral venous access is limited, because this has been discouraged due to the high incidence of infectious or thromboembolic complications . We evaluated the safety and efficacy of 108 short-term femoral venous dialysis catheters used for the collection of peripheral blood stem cells (PBSCs) . All catheters were placed by a member of the dialysis unit, and they remained in situ for the days needed to reach the target number of CD34+cells . No prophylactic antibiotic or antithrombotic therapy was used . A total of 232 apheresis sessions was performed . The longest duration a catheter remained in situ was 5 days . Most of the patients finished the collection in one or two apheresis sessions . There were no thrombotic or infectious complications, and insertion-related complications or mechanical problems were minimal . Apheresis results were similar to those reported using subclavian or jugular venous access . The short-term use of femoral venous dialysis catheters appears safe and effective for PBSC collection, simplifying the procedure, improving patient comfort, and reducing cost. J Oral Pathol Med, 2004 Jan, 33(1), 37 - 45 MEK inhibition enhances bleomycin A5-induced apoptosis in an oral cancer cell line: signaling mechanisms and therapeutic opportunities; Yang LC et al.; BACKGROUND: Bleomycin A5 is an anti-neoplastic glycoprotein antibiotic used for the treatment of various cancers . Previous work has shown that bleomycin A5 exerts its apoptotic effects on tumor cells . This was to study the signal transduction pathways that might exert the apoptotic effects of bleomycin A5 on tumor cells, as well as to examine the possibility of lower dosing of such drug in combinative treatment with other compounds in vitro . METHODS: Bleomycin A5 was applied on a human oral epidermoid carcinoma cell line, human oral epidermoid carcinoma (KB), and the apoptotic activity was determined by the presence of DNA fragmentation and 4,6-diamidino-2-phenylindole (DAPI) nuclear staining . The signal transduction pathway was measured through Western blotting and in vitro kinase assay . RESULTS: The apoptotic effect was associated with the sustained activation of c-Jun N-terminal kinases (JNK) and the inhibition of extracellular signal-regulated kinases1 (ERK1) and -2 activities, suggesting that JNK plays a positive role in the death process . ERK1 and -2 might exert a protection pathway from cell death . Here, it was determined that a combination treatment of bleomycin A5 and the MAP kinase-ERK kinase (MEK) inhibitor, PD98059, could lead to enhanced apoptosis . The activities of ERK1 and -2 are required for cell survival signaling using stable cell clones expressing MEK1 . Upon bleomycin A5 treatment, cells expressing MEK1 exhibited significant delays in the onset of apoptosis, where the presence of MEK1 inhibitor enhanced cell death . Moreover, the increased activity of ERK1 and -2 coincided with cell survival . The survival signals exerted by MEK1 most likely result from the activation of ERK1 and -2 . CONCLUSIONS: The apoptosis enhancement through such combinative treatment in vitro has revealed new therapeutic opportunities and elucidated mechanisms contributing to the efficacy of existing anti-cancer treatments. J Oral Pathol Med, 2004 Jan, 33(1), 17 - 22 Prevalence of oral mucosal alterations in children from 0 to 12 years old; Bessa CF et al.; BACKGROUND: As the exact prevalence of oral alterations in children is still not known and the findings are controversial, other studies about this subject are necessary . METHODS: A cross-sectional survey was carried out on 1211 Brazilian children divided in two age groups: 0-4 and 5-12 years . The patients were economically classified and data of medical history were obtained from medical records . RESULTS: The frequency of children presenting alterations was 27.0%, and it was higher in older children . The most common lesions were geographic tongue, cheek biting, and melanotic macule . Candidiasis was associated with antibiotic therapy and use of pacifiers . Fissured tongue was associated with congenital anomalies, allergy; age from 5 to 12 years . There was a lack of association of patient's economic status and prevalence of oral mucosal alterations . CONCLUSIONS: The frequency of mucosal alterations in children is high and increases with age, and some of them are associated with habits and medical history of the patients. Hosp Med, 2003 Nov, 64(11), 644 - 7 The role of infection in preterm labour and birth; Lamont RF; Preterm birth is the major cause of neonatal mortality and morbidity . Infection is a major cause of preterm labour . Abnormal genital tract flora in early pregnancy is predictive of preterm labour . Antibiotics may be of help in preventing preterm birth. Stomatologiia (Mosk), 2003, 82(6), 27 - 31 {Lymphotropic therapy for acute purulent odontogenic jaw periostitis}; Maiborodin IV et al.; The structure of the gingival mucosa was studied by optic microscopy in patients with acute purulent odontogenic maxillary periostitis treated traditionally and receiving lymphotropic therapy . Lymphotropic administration of the antibiotic during 2 days resulted in less pronounced dilatation of the interstitial spaces and lymph vessels adjacent to the molars and higher counts of lymphocytes, monocytes, and macrophages . This indicated high efficiency of lymphotropic therapy of acute purulent maxillary periostitis for molars . Microcirculation parameters and tissue leukocyte cytogram in gingival mucosal tissue adjacent to the canines and premolars differed negligibly in patients treated by different methods. J Biol Chem, 2004 Mar 5, 279(10), 8708 - 14 Epub 2003 Dec 10. Inhibition of the yeast cytochrome bc1 complex by ilicicolin H, a novel inhibitor that acts at the Qn site of the bc1 complex; Gutierrez-Cirlos EB et al.; Ilicicolin H is an antibiotic isolated from the "imperfect" fungus Cylindrocladium iliciola strain MFC-870 . Ilicicolin inhibits mitochondrial respiration by inhibiting the cytochrome bc(1) complex . In order to identify the site of ilicicolin action within the bc(1) complex we have characterized the effects of ilicicolin on the cytochrome bc(1) complex of Saccharomyces cerevisiae . Ilicicolin inhibits ubiquinol-cytochrome c reductase activity of the yeast bc(1) complex with an IC(50) of 3-5 nM, while 200-250 nM ilicicolin was required to obtain comparable inhibition of the bovine bc(1) complex . Ilicicolin blocks oxidation-reduction of cytochrome b through center N of the bc(1) complex and promotes oxidant-induced reduction of cytochrome b but has no effect on oxidation of ubiquinol through center P . These results indicate that ilicicolin binds to the Qn site of the bc(1) complex . Ilicicolin induces a blue shift in the absorption spectrum of ferro-cytochrome b, and titration of the spectral shift indicates binding of one inhibitor molecule per Qn site . The effects of ilicicolin on electron transfer reactions in the bc(1) complex are similar to those of antimycin, another inhibitor that binds to the Qn site of the bc(1) complex . However, because the two inhibitors have different effects on the absorption spectrum of cytochrome b, they differ in their mode of binding to the Qn site. J Womens Health (Larchmt), 2003 Nov, 12(9), 897 - 902 Medical treatment of women and adherence to HIV guidelines at an urban university-staffed public clinic; Parikh MJ et al.; BACKGROUND: HIV-related morbidity and mortality have declined in recent years in the United States . Relative to their male counterparts, however, HIV-infected women tend to have less reduced morbidity and mortality . The purpose of this study was to investigate if the reported small decreases in HIV-related morbidity and mortality in women could be due to their receiving a lesser standard of care from public health clinics . METHODS: One hundred sixteen female and 131 male patients who were diagnosed with HIV infection were drawn consecutively from a county-owned health clinical database in Houston, Texas . Physicians from the two local medical schools staffed the clinic . Information on patients' demographic characteristics, screening tests, clinical care, and prophylaxis care was abstracted for comparison . Results and Conclusions: The data showed that there were no statistically significant sex-based differences in getting access to antiretroviral treatment or for prophylaxis of opportunistic infections in the clinic . Sex-based differences, however, were found in the initial CD4 cell count and HIV load . Women had higher CD4 cell counts and HIV RNA levels at the initial stage and during the time of treatment. J Womens Health (Larchmt), 2003 Nov, 12(9), 889 - 95 The challenges of informed consent for rapid HIV testing in labor; Jamieson DJ et al.; BACKGROUND: Although increasing attention has been focused on the adequacy of the informed consent process for participation in research studies, there has been little systematic evaluation of the process, particularly when consent is obtained in the labor and delivery setting . The Mother Infant Rapid Intervention at Delivery (MIRIAD) study is an ongoing multisite study initiated by the Centers for Disease Control and Prevention (CDC) designed to evaluate the feasibility of offering 24-hour counseling and voluntary rapid HIV testing and antriretroviral therapy when indicated to women with unknown HIV status who are in labor . METHODS: To address concerns about obtaining informed consent from women in labor, we have completed focus groups, conducted a pilot of the informed consent process among women in labor, developed flip-charts to enhance comprehension, and plan an ongoing evaluation of the informed consent process throughout the course of the MIRIAD study . RESULTS: In the pilot study, approximately 70% of women were able to state in their own words the purpose and benefits of the research study . Substantially fewer women (25%) were able to state one or more risks of the study . CONCLUSIONS: We hope that the MIRIAD study will make a valuable contribution by defining best approaches for informed consent and will provide guidance when it is necessary to obtain consent from laboring women for crucial interventions. J Environ Pathol Toxicol Oncol, 2003, 22(4), 281 - 6 Clastogenic effects of streptozotocin on human colon cancer cell lines with gene amplification; Bolzan AD et al.; We investigated the clastogenic effects of the methylating agent streptozotocin (STZ) on two human colon cancer cell lines . COLO320DM and COLO320HSR are cell lines derived from a human neuroendocrine colon carcinoma . STZ produced a dose-dependent increase in the frequency of chromosomal aberrations in both cell lines (p < 0.05) and induced fragmentation and/or pulverization of COLO320DM and COLO320HSR chromosomes . This effect was dose and time dependent . Severe chromosome damage was also found in cells that had progressed beyond the first metaphase, and a higher percentage of metaphases showing pulverized chromosomes were found in cells after the second than after the first division . This seems to indicate that STZ has a persistent and delayed clastogenic effect on COLO320DM and COLO320HSR cells . In addition, STZ produced a marked depression of the mitotic index in both cell lines . These results demonstrate that human colon cancer cell lines COLO320DM and COLO320HSR are highly sensitive to STZ, and suggest that this antibiotic has a good potential as a chemotherapeutic agent for colon cancer. Fertil Steril, 2003 Dec, 80(6), 1371 - 5 Uterine cavity findings and hysteroscopic interventions in patients undergoing in vitro fertilization-embryo transfer who repeatedly cannot conceive; Oliveira FG et al.; OBJECTIVE: To assess hysteroscopic findings in patients undergoing IVF-ET who repeatedly failed to conceive despite transfer of good-quality embryos . DESIGN: Prospective, observational study . SETTING: Clinical research unit for reproductive medicine in a private clinic . PATIENT(S): Fifty-five patients with a normal uterine cavity on hysterosalpingography before the initial IVF-ET cycle and two previous failed IVF-ET attempts despite transfer of a minimum of two good-quality embryos on each occasion . INTERVENTION(S): Standard transvaginal ultrasonography and diagnostic and therapeutic hysteroscopy . MAIN OUTCOME MEASURE(S): Endometrial findings on transvaginal ultrasonography and hysteroscopy and outcome of the cycles after surgical hysteroscopy and antibiotic therapy . RESULT(S): Twenty-five (45%) patients had abnormal endometrial findings and underwent treatment to correct the lesions . All patients underwent a third IVF-ET cycle . Pregnancy (50% vs . 20%) and implantation (19% vs . 5.5%) rates were significantly higher in patients who were treated for uterine abnormalities than in patients who had normal uterine cavities on hysteroscopy . CONCLUSION(S): The incidence of pathologic findings on hysteroscopy is high in patients with repeated failures of IVF-ET . Evaluation of endometrial integrity by hysteroscopy is highly valuable and should be applied to all such cases. G Ital Nefrol, 2003 Sep-Oct, 20 Suppl 24, S109 - 28 {Guidelines of the Italian Society of Nephrology . Peritoneal dialysis Guidelines}; Cancarini GC; Italian Society of Nephrology; The adequate dosage of peritoneal dialysis (PD) has been defined (using unrandomized and uncontrolled studies) asKt/V = 2, with a total (peritoneal + renal) creatinine clearance = 60 mL/min . The recent prospective, randomized ADEMEX study, suggests targets of 1.8 and 54 mL/min respectively . Dialysis must also be adequate to control fluid removal, phosphate levels, nutritional status, and hypertension . The targets for automated PD (APD) should be either 10% more than CAPD or similar, depending on the time of blood sample collection either immediately at the end of the automated exchanges or 6 to 8 hours after . A peritoneal equilibration test should be done 1 to 2 months after the start of PD, yearly, and when peritoneal permeability or ultrafiltration changes occurr . Residual renal function must be protected as long as possible by avoiding nephrotoxic drugs and excessive dehydration . Every effort must be taken in the attempt to maintain a good nutritional status and to diagnose as soon as possible any changes toward malnutrition . Hypertension has a high prevalence in PD patients and has negative effects on both cardiovascular status and patient survival . However, anti-hypertensive therapy should avoid hypotension, mainly in older patients, who are more at risk for cerebrovascular accident . Hyperparathiroidism must be controlled by diet, phosphate binders, and calcitriol supplement, but attention must be paid to avoid cardiac and vascular calcifications . Peritonitis and exit-site infection should be prevented by all means available . In the case of infection, empiric antibiotic therapy should be started as soon as possible and then adapted according to the antibiogram. J Pediatr Surg, 2003 Dec, 38(12), 1826 - 9 The intussusception antireflux valve is ineffective for preventing cholangitis in biliary atresia: a prospective study; Ogasawara Y et al.; PURPOSE: Cholangitis after Kasai portoenterostomy for biliary atresia (BA) strongly influences outcome, and an intussusception antireflux valve (IAV) in the Roux-en-Y limb has been advocated for the prevention of cholangitis without definitive evidence . The authors report a prospective study to evaluate the effectiveness of IAV in BA . METHODS: Twenty-one consecutive patients with uncorrectable-type BA were the subjects for this study . IAV was included based on informed parental request to give 2 groups: IAV- (n = 11) and IAV+ (n = 10) . The incidence/duration of episodes of cholangitis (temperature > 38 degrees C, elevated serum bilirubin level, and leukocytosis) during the first 6 months after Kasai were statistically compared between the 2 groups (P >.05 was regarded as not significant) . RESULTS: Technical variations in surgical technique were minimized because the same surgeon supervised all procedures . There were no significant differences between the 2 groups for age and weight at the time of Kasai, mean size of bile ductules at the porta hepatis, and degree of liver cirrhosis present . Protocols for antibiotic and steroid therapy were the same for both groups . The total number of patients who had cholangitis in the IAV- group was 6 of 11 and 5 of 10 in the IAV+ group (P = NS) . The total number of episodes of cholangitis was 16 in the IAV- group versus 17 in the IAV+ group (P value, not significant) . The mean duration of an episode of cholangitis (number of days per number of episodes) was 12 +/- 6 days in the IAV- group versus 11 +/- 7 days in the IAV+ group (P value, not significant) . CONCLUSIONS: IAV does not make any significant impact on the incidence or duration of cholangitis in the early post-Kasai period. Proc Natl Acad Sci U S A, 2003 Dec 23, 100(26), 15930 - 5 Epub 2003 Dec 09. Arf tumor suppressor promoter monitors latent oncogenic signals in vivo; Zindy F et al.; Induction of the Arf tumor suppressor gene by elevated thresholds of mitogenic signals activates a p53-dependent transcriptional response that triggers either growth arrest or apoptosis, thereby countering abnormal cell proliferation . Conversely, Arf inactivation is associated with tumor development . Expression of Arf in tissues of adult mice is difficult to detect, possibly because its induction leads to the arrest or elimination of incipient tumor cells . We replaced coding sequences of exon 1beta of the mouse cellular Arf gene with a cDNA encoding GFP, thereby producing Arf-null animals in which GFP expression is driven by the intact Arf promoter . The Arf promoter was induced in several biologic settings previously shown to elicit mouse p19Arf expression . Inactivation of Arf in this manner led to the outgrowth of tumor cells expressing GFP, thereby providing direct evidence that the Arf promoter monitors latent oncogenic signals in vivo. J Biol Chem, 2004 Feb 27, 279(9), 7606 - 12 Epub 2003 Dec 09. Evidence for radical formation at Tyr-353 in Mycobacterium tuberculosis catalase-peroxidase (KatG); Zhao X et al.; Mycobacterium tuberculosis KatG is a heme-containing catalase-peroxidase responsible for activation, through its peroxidase cycle, of the front line antituberculosis antibiotic isoniazid (isonicotinic acid hydrazide) . Formation of Compound I (oxyferryl heme-porphyrin pi-cation radical), the classical peroxidase intermediate generated when the resting enzyme turns over with alkyl peroxides, is rapidly followed by production of a protein-centered tyrosyl radical in this enzyme . In our efforts to identify the residue at which this radical is formed, nitric oxide was used as a radical scavenging reagent . Quenching of the tyrosyl radical generated in the presence of NO was shown using electron paramagnetic resonance spectroscopy, and formation of nitrotyrosine was confirmed by proteolytic digestion followed by high performance liquid chromatography analysis of the NO-treated enzyme . These results are consistent with formation of nitrosyltyrosine by addition of NO to tyrosyl radical and oxidation of this intermediate to nitrotyrosine . Two predominant nitrotyrosine-containing peptides were identified that were purified and sequenced by Edman degradation . Both peptides were derived from the same M . tuberculosis KatG sequence spanning residues 346-356 with the amino acid sequence SPAGAWQYTAK, and both peptides contained nitrotyrosine at residue 353 . Some modification of Trp-351 most probably into nitrosotryptophan was also found in one of the two peptides . Control experiments using denatured KatG or carried out in the absence of peroxide did not produce nitrotyrosine . In the mutant enzyme KatG(Y353F), which was constructed using site-directed mutagenesis, a tyrosyl radical was also formed upon turnover with peroxide but in poor yield compared with wild-type KatG . Residue Tyr-353 is unique to M . tuberculosis KatG and may play a special role in the function of this enzyme. J Agric Food Chem, 2003 Dec 17, 51(26), 7523 - 7 Determination of the fungicide validamycin A by capillary zone electrophoresis with indirect UV detection; He J et al.; Validamycin A, a main component of the antibiotic validamycin complex, which is widely used to control sheath blight disease of rice plants, can be determined by capillary zone electrophoresis with indirect UV detection . The influence of various separation conditions including background electrolyte and modifier concentration, pH, and voltage was investigated . By using 10 mM aminopyrine-2 mM ethylenediaminetetraacetic acid at pH 5.2 as the carrier electrolyte, high efficiency separation of validamycin A was achieved with the number of theoretical plates up to 350000 plates/m . The linear range was across 3 orders of magnitude . The relative standard deviations for migration times and peak areas were less than 0.5 and 3.0%, respectively . The limit of detection for validamycin A was 1.0 microg/mL . The average recoveries ranged from 103.0 to 104.8% . This method has many advantages as compared with high-performance liquid chromatography and micellar electrokinetic capillary chromatography in the determination of commercial formulations. J Pept Sci, 2003 Nov-Dec, 9(11-12), 690 - 700 Self-assembling and membrane modifying properties of a lipopeptaibol studied by CW-ESR and PELDOR spectroscopies; Milov AD et al.; Trichogin GA IV is a short lipopeptaibol antibiotic that is capable of enhancing the transport of small cations through the phospholipid double layer of the membrane . The antibiotic activity of the undecapeptide is thought to be based on either its self-assembling or membrane-modifying property . The chemical equilibrium between self-aggregated and non-aggregated molecular states was studied by CW-ESR spectroscopy using solutions of TOAC nitroxide spin-labelled trichogin analogues in an apolar solvent to mimic the membrane bound state . At room temperature the two different sets of signals observed in the spectrum were attributed to the presence of both monomers and aggregates in the sample . The ESR spectra of the monomeric and aggregated forms were separated and the dependence of the fraction of monomeric peptide molecules on concentration was obtained over the range 5 x 10(-6) to 7 x 10(-4) M . A two-step aggregation mechanism is proposed: dimerization of peptide molecules followed by aggregation of dimers to assemblies of four peptide molecules per aggregate . The equilibrium constants were estimated for both steps . In addition, the lower lifetime limit was determined for dimers and tetramers . It is shown that when the peptide concentration exceeds 10(-5) M . the major part of the peptide molecules in solution has the form of tetrameric aggregates . Independently, the PELDOR technique was used to investigate the concentration dependence of the parameters of the dipole-dipole interaction between spin labels in frozen (77 K} glassy solutions of aggregates of mono-labelled TOAC analogues . The number of molecules in aggregates as well as the frequency and amplitude of PELDOR signal oscillations were found to be concentration independent in the range 5 x 10(-4) to 8 x 10(-3) M . In the frozen glassy solution state, the number of peptide molecules per aggregate was determined to be close to four, which is in agreement with the value obtained for spin-labelled trichogin at room temperature . The present data provide experimental evidence in favour of a self-assembling rather than a membrane-modifying ion conduction mechanism. Z Kardiol, 2003 Dec, 92(12), 1029 - 32 {Lyme carditis and symptomatic sinus node dysfunction}; Franck H et al.; Lyme carditis is typically associated with AV nodal conduction abnormalities . We describe the case of a 66 year old female patient, who experienced a series of syncopal attacks after several tick bites two weeks earlier . ECG monitoring revealed recurrent sinus arrest with a maximum pause duration of 8 seconds . After institution of antibiotic therapy for Lyme carditis, sinus node dysfunction resolved rapidly and the patient had no further syncopes . Pacemaker implantation was not necessary . We therefore have to assume that in this patient Lyme carditis was the cause of symptomatic sinus node dysfunction. J Obstet Gynaecol Can, 2003 Dec, 25(12), 1020 - 5 Influenza-like illness during pregnancy: results from a study in the eastern townships, Province of Quebec; Tuyishime JD et al.; OBJECTIVES: (1) To assess the frequency of influenza and influenza-like illness (ILI) during pregnancy; (2) to explore the associated risk of adverse maternal and fetal outcomes . METHODS: All women who delivered at the Sherbrooke University Hospital in the province of Quebec during the period of February 15 to April 30, 2002, were invited to complete a questionnaire . Medical records of participating women and of their infants were reviewed . Complement-fixing antibody titres against influenza A were measured in paired sera drawn during antenatal screening and at delivery . RESULTS: The study participation rate was 96.3% . Nine of 517 women stated that they had received the influenza vaccine during pregnancy, and only 3 of 47 women with a chronic pulmonary disease had been immunized . Overall, 464 ILI episodes were reported by 331 women, and a significant maternal complication occurred in 8 cases . ILI episodes resulted in medical consultations in 55.4% of cases, and in antibiotic prescriptions in 13.8% of cases . There was no indication of an increased frequency of adverse perinatal outcomes associated with ILI during pregnancy . Paired sera were available for 156 participants and seroconversion was observed in 6.6% . CONCLUSIONS: ILI during pregnancy was associated with health services utilization but complications were infrequent . More studies are needed to demonstrate the usefulness of routine vaccination of healthy pregnant women against influenza. Presse Med, 2003 Nov 8, 32(36), 1699 - 704 {Elderly patients presenting with fever and respiratory problems in an intensive care unit . Diagnostic, therapeutic and prognostic impact of a systematic infectious disease consultation}; Roger PM et al.; OBJECTIVE: To measure the impact of an infectious disease consultation on the morbidity and mortality in patients aged over 75 presenting with fever and respiratory signs and treated with antibiotics in an intensive care unit . METHOD: Retrospective study comparing two groups of patients having been seen or not by an infectious disease specialist within the first 24 hours of hospitalisation . The data available before prescription of the antibiotherapy by the intensive care physician were collected, together with the diagnostic and therapeutic proposals of the infectious disease specialist . Morbidity and mortality were assessed from the medical files and nurses charts and included: duration of fever and hospitalisation, complications with antibiotherapy and venous catheters and the cause or causes of death . RESULTS: 169 patients were included, 115 of whom had been seen (study group) and 54 who had not bee seen (control group) by an infectious disease specialist . Sixty-six percent of the infectious disease specialists (76/115) proposed a differential diagnosis, although a diagnostic re-assessment was effective for only 22% of the patients in the control group (p< 0.01) . A 50% reduction in antibiotic prescriptions was observed in the study group . The duration of hospitalisation was greater in the study group than in the control group (a mean of 10 versus 7 days, p<0.01), but was unrelated to the consultation with a specialist . The same result was observed with the complications of venous catheterism (16 versus 2 cases, p =0.04) . The rate of mortality was of 13% in both groups . CONCLUSION: The over-zealous diagnoses of infection are the primary cause of over-prescription of antibiotics . Despite the population studied, considered as fragile, the 50% reduction in antibiotics is without any negative prognostic impact. Presse Med, 2003 Nov 22, 32(37 Pt 1), 1734 - 6 {The level of knowledge of general practitioners regarding the early phase of Lyme borreliosis . Survey conducted among 106 general practitioners}; Lieber M'bomeyo A et al.; OBJECTIVE: Determine the level of knowledge of the general practitioners on the early phase of Lyme borreliosis in an endemic area and notably to define the attention paid to the use and interpretation of serologic investigations for the treatment of patients with erythema migrans . METHOD: This was a prospective study conducted from May 15 to June 31, 2001 among 106 randomly selected general practitioners installed in Strasbourg, France . The practitioners were all interviewed in their private practice and by the same person . Three standardized questions were asked, evaluating their level of specific medical training on Lyme borreliosis as well as their practice regarding treatment and diagnosis of erythema migrans . RESULTS: One third of the general practitioners had already accomplished a continued medical education course on Lyme borreliosis . Half of them considered that the diagnosis of erythema migrans was clinical, while the other half believed that serological confirmation was mandatory . However, the answers of those having received specific education on borreliosis were right (p=0.0079) since in this sub-group 72% considered that the diagnosis was exclusively based on clinical examination, versus 41% of the untrained physicians . Eighty-eight percent used the recommended antibiotic regimens to treat erythema migrans . Three practitioners proposed an inefficient treatment that had exposed the patients to the risk of extra-cutaneous complications of the disease . CONCLUSION: Fifty percent of the general practitioners working in endemic areas for Lyme borreliosis still believe that seropositivity against Borrelia burgdorferi is required to diagnose erythema migrans, which is untrue . However, this study shows that a specific education on Lyme borreliosis would significantly improve this score. Presse Med, 2003 Nov 29, 32(38), 1792 - 6 {Survey on the treatment of hospitalised community-acquired lower respiratory tract infections}; Villani P et al.; OBJECTIVES: The assessment of treatment habits regarding community-acquired lower respiratory tract infections and comparison with current national recommendations . METHOD: Prospective survey of treatment habits . Patients hospitalised for community-acquired pneumonia in the department of internal medicine, the department of neurology and the department of respiratory diseases (127 beds) at the Sainte-Marguerite Hospital in Marseilles were included . We studied the socio-economical context, the presence of severity factors, the analysis of risk factors, the antibiotic treatments prescribed (type, route of administration, duration) and the outcome of the patients . RESULTS: From November 2001 to February 2002, 98 patients with community-acquired pulmonary infections were included (61 men with a mean age of 72.5 years) . The treatment of these patients conformed to guidelines in 79 cases . In 19 cases, the prescription did not conform (unjustified bi-therapy in 8 patients; absence of bi-therapy in suspected cases of intra-cellular bacteria in 4 patients; insufficient dose in 2 patients; and non-adapted antibiotherapy in 5 patients) . CONCLUSION: In the study conditions, the management of community-acquired pneumonia in the hospital most often conformed to current guidelines . Nevertheless, efforts made for initial and continued medical training together with the wide circulation of the guidelines must be continued. J Chromatogr A, 2003 Dec 12, 1020(2), 241 - 50 Determination of lincomycin and tylosin residues in honey using solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization mass spectrometry; Thompson TS et al.; An analytical method for the determination of residues of the antibiotic drugs lincomycin and tylosin in honey was developed . The procedure employed a solid-phase extraction for the isolation of lincomycin and tylosin from diluted honey samples . The antibiotic residues were subsequently analyzed by reversed-phase HPLC with atmospheric pressure chemical ionization mass spectrometric detection . Average analyte recoveries for lincomycin and tylosin ranged from 84 to 107% in replicate sets of honey samples fortified with drug concentrations of 0.01, 0.5, and 10 microg/g . The method detection limits were determined to be 0.007 and 0.01 microg/g for lincomycin and tylosin, respectively. Shanghai Kou Qiang Yi Xue, 2003 Feb, 12(1), 58 - 61 {A clinical study on septic arthritis of temporomandibular joint: treatment}; Yang C et al.; OBJECTIVE: To investigate the procedure and effect on treating septic arthritis of temporomandibular joint (TMJ) . METHODS: 30 patients were treated by antibiotic therapy, resting of the jaw, and local therapies . The local therapies included arthrocentesis with single needle in 20 joints, arthrocentesis with double needles in 13, arthrocentesis accompanied by submandibular drainage of the infratemporal space abscess in 1, and arthroscopy in 4 . The therapeutic effects were judged by joint cavity puncture, mouth opening, jaw pain, and jaw function, and so on . Sequelae were evaluated . RESULTS: The overall success rate of the treatment was 100% (30/30) . The success rates of the 4 different management were: 14/20 in arthrocentesis with single needle, 9/13 in arthrocentesis with double needles, 1/1 in arthrocentesis combined with submandibular drainage, and 4/4 in arthroscopy, respectively . The sequelae were mild, and most of the cases had only postinfectious osteoarthritis . CONCLUSIONS: Low pressure arthrocentesis, antibiotic therapy and resting of the jaw were important components of treatment in acute septic arthritis . If infratemporal space abscess was found, submandibular drainage should be done . Arthroscopy could be recommended to those who haven't got good results by arthrocentesis or those who have already had some sequelae, such as TMJ fibrous ankylosis. J Biol Chem, 2004 Feb 27, 279(9), 8242 - 51 Epub 2003 Dec 02. Identification and molecular characterization of the beta-ketoacyl-{acyl carrier protein} synthase component of the Arabidopsis mitochondrial fatty acid synthase; Yasuno R et al.; Substrate specificity of condensing enzymes is a predominant factor determining the nature of fatty acyl chains synthesized by type II fatty acid synthase (FAS) enzyme complexes composed of discrete enzymes . The gene (mtKAS) encoding the condensing enzyme, beta-ketoacyl-{acyl carrier protein} (ACP) synthase (KAS), constituent of the mitochondrial FAS was cloned from Arabidopsis thaliana, and its product was purified and characterized . The mtKAS cDNA complemented the KAS II defect in the E . coli CY244 strain mutated in both fabB and fabF encoding KAS I and KAS II, respectively, demonstrating its ability to catalyze the condensation reaction in fatty acid synthesis . In vitro assays using extracts of CY244 containing all E . coli FAS components, except that KAS I and II were replaced by mtKAS, gave C(4)-C(18) fatty acids exhibiting a bimodal distribution with peaks at C(8) and C(14)-C(16) . Previously observed bimodal distributions obtained using mitochondrial extracts appear attributable to the mtKAS enzyme in the extracts . Although the mtKAS sequence is most similar to that of bacterial KAS IIs, sensitivity of mtKAS to the antibiotic cerulenin resembles that of E . coli KAS I . In the first or priming condensation reaction of de novo fatty acid synthesis, purified His-tagged mtKAS efficiently utilized malonyl-ACP, but not acetyl-CoA as primer substrate . Intracellular targeting using green fluorescent protein, Western blot, and deletion analyses identified an N-terminal signal conveying mtKAS into mitochondria . Thus, mtKAS with its broad chain length specificity accomplishes all condensation steps in mitochondrial fatty acid synthesis, whereas in plastids three KAS enzymes are required. J Biol Chem, 2004 Feb 20, 279(8), 6847 - 52 Epub 2003 Dec 01. Geldanamycin-associated inhibition of intracellular trafficking is attributed to a co-purified activity; Barzilay E et al.; Geldanamycin, an ansamycin antibiotic that specifically inhibits heat-shock protein-90 (HSP90) and its endoplasmic reticulum homologue, glucose-regulated protein-94 (GRP94), accelerates the degradation of selected cellular proteins . We showed previously that geldanamycin inhibits maturation and transport of the epidermal growth factor receptor in addition to accelerating its degradation (Supino-Rosin, L., Yoshimura, A., Yarden, Y., Elazar, Z., and Neumann, D . (2000) J . Biol . Chem . 275, 21850-21855) . Here we demonstrate that the additional activities of geldanamycin on intracellular transport and protein maturation are related to its supply source . By combining chemical separation of Streptomyces hygroscopicus var . geldanus extracts and biological screens, we show that the geldanamycin-associated effects on intracellular transport and protein maturation are not mediated by geldanamycin itself but are due to the presence of an additional component(s) . Chromatography of S . hygroscopicus var . geldanus extracts on a silica-gel column allowed separation between the inhibition of intracellular trafficking and geldanamycin-mediated degradation . One fraction that was devoid of geldanamycin blocked secretion of a soluble form of the erythropoietin receptor, retarded maturation of the epidermal growth factor receptor without enhancing its degradation, and blocked anterograde transport of a temperature-sensitive mutant of the vesicular stomatitis virus G protein (VSVGtsO45) from the early Golgi cisternae . This fraction was enriched (>95%) in 17-demethylgeldanamycin . However, as synthetically derived 17-demethylgeldanamycin did not inhibit intracellular trafficking, we concluded that 17-demethylgeldanamycin is not the active component . We thus propose that a compound(s) that co-purifies with benzoquinone ansamycins inhibits intracellular transport . Taken together, our data demonstrate that the inhibitory effects on protein maturation and intracellular trafficking, previously attributed to geldanamycin, are mediated by another distinct moiety. Ann Chir, 2003 Nov, 128(9), 630 - 2 {Perineal necrotizing cellulitis disclosing rectal adenocarcinoma}; Lamy A et al.; We report one case of rectal cancer disclosed by a perineal cellulitis in a diabetic woman . This infrequent association has a bad prognosis . Diagnosis is mainly clinical . Treatment is urgent with large spectrum antibiotic therapy, surgical debridement, colostomy and hyperbaric oxygen if available . Surgical treatment of the rectal cancer can be done immediately or delayed. J Heart Valve Dis, 2003 Nov, 12(6), 741 - 51 Mineralization and organic phase modifications as contributory factors of accelerated degeneration in homograft aortic valves; Lis GJ et al.; BACKGROUND AND AIM OF THE STUDY: The study aim was to assess histological and mineralogical properties of leaflets in human, antibiotic-preserved aortic homograft valves (recovered during surgical replacement) in order to identify factors accounting for pathological changes leading to accelerated graft dysfunction . A comparison was made with aortic valves prepared for grafting, with a view to assessing morphological and mineralogical characteristics as a potential preimplantation risk factor . METHODS: Valve leaflets were examined with light and scanning electron microscopy . Mineralization was assessed histochemically, and also physicochemically by atomic absorption spectroscopy (AAS) . RESULTS: All explanted homograft valve leaflets revealed prominent degenerative changes seen as decreased surface area, fibrosis, mineralization and focal thrombosis . Substantial loss of endothelium and fibroblasts, reduced collagen bundles crimping, inflammation (81%) and disappearance of layered structure (59%) was identified . The elastic elements were relatively stable, though a gradual age-dependent loss was observed in both groups . Accelerated mineralization was seen in all explanted homografts; inorganic deposits were composed mainly of hydroxyapatite . Two types of mineralization were identified: large limited nodular structures, and diffuse mineral deposits . Homografts with moderately elevated mineralization, well-preserved layered structure and sporadic infective changes proved to have the greatest durability . Homograft durability was also affected by the difference in host and donor age . CONCLUSION: Preimplantation factors affecting pathological changes determining homograft durability included morphological status of the graft itself and donor age; host-related factors included recipient age, endocarditis, native valve calcification, and host-donor matching (age difference between host and donor) . A limited molecular mineralization may increase valvular durability, provided that no focal nodular calcifications exist that might adversely affect overall homograft integrity. J Pept Sci, 2003 Nov-Dec, 9(11-12), 776 - 83 Channel properties of template assembled alamethicin tetramers; Duclohier H et al.; The multiple conductance levels displayed by the antibiotic alamethicin in planar lipid bilayers is explained by a dynamic 'barrel-stave' model, the conducting pore resulting from the aggregation of up to ten helical amphipathic helical monomers . However, the precise assignment of an oligomerization state to a particular single-channel conductance substate is far from being experimentally clear . In addition, it could be useful to tailor a given channel geometry to selectively allow the permeation of solutes with different molecular sizes, whilst retaining a high voltage-dependence . To control the aggregation state of the channel, the TASP (template assembled synthetic proteins) strategy was applied to synthesize structurally defined oligomers, i.e . dimer, trimer, tetramer . The modulation of conductance properties of three alamethicin tetramers with the length and flexibility of the linkers of the 'open' or linear template is described . It is shown that the introduction of an alanine between the contiguous lysines to which are tethered C-terminally modified alamethicin helical monomers stabilizes the open channel states, whereas the alanine substitution by Pro-Gly, a reverse beta-turn promoting motif, increases voltage-dependence and leads to single-channel conductance values more in line with the expected ones from a tetrameric bundle. J Pept Sci, 2003 Nov-Dec, 9(11-12), 769 - 75 The peptaibol antiamoebin as a model ion channel: similarities to bacterial potassium channels; O'Reilly AO et al.; Antiamoebin (AAM) is a polypeptide antibiotic that is capable of forming ion channels in phospholipid membranes: planar bilayer studies have suggested the channels are octamers . The crystal structure of a monomeric form of AAM has provided the basis for molecular modelling of an octameric helical bundle channel . The channel model is funnel-shaped due to a substantial bend in the middle of the polypeptide chain caused by the presence of several imino acids . Inter-monomer hydrogen bonds orientate a ring of glutamine side chains to form a constriction in the pore lumen . The channel lumen is lined both by side chains of Gln11 and by polypeptide backbone carbonyl groups . Electrostatic calculations on the model are compatible with a channel that transports cations across membranes . The AAM channel model is compared with the crystal structures of two bacterial (KcsA andMthK) potassium channels . AAM and the potassium channels exhibit common functional features, such as cation-selectivity and similar single channel conductances . Common structural features include being multimers, each formed from a bundle of eight transmembrane helices, with lengths roughly comparable to the thickness of lipid bilayers . In addition, they all have aromatic amino acids that lie at the bilayer interfaces and which may aid in the stabilization of the transmembrane helices, as well as narrower constrictions that define the ion binding sites or selectivity filters in the pore lumen . The commonalit