Antibiotics

J Chromatogr A, 2004 Mar 26, 1031(1-2), 171 - 8
Direct and indirect high-performance liquid chromatographic enantioseparation of beta-amino acids; Peter A et al.; Direct and indirect reversed-phase (RP) high-performance liquid chromatographic methods were developed for the separation of enantiomers of 18 unnatural beta-amino acids, including several beta-3-homo amino acids . The direct separations of the underivatized analytes were performed on chiral stationary phases (CSPs) containing macrocyclic glycopeptide antibiotic teicoplanin (Chirobiotic T column) and teicoplanin aglycone (Chirobiotic TAG column) . The indirect method involved pre-column derivatization with a new chiral derivatizing agent (CDA), (S)-N-(4-nitrophenoxycarbonyl)phenylalanine methoxyethyl ester ((S)-NIFE), and subsequent separation of diastereomers on Discovery C18 and Hyperpep 300 C18 columns . The different methods were compared in systematic chromatographic examinations . The effects of organic modifier, mobile phase composition, pH and flow rate on the separation were investigated.

J Chromatogr A, 2004 Mar 26, 1031(1-2), 159 - 70
Comparison of the separation efficiencies of chirobiotic T and TAG columns in the separation of unusual amino acids; Peter A et al.; Two macrocyclic antibiotic type chiral stationary phases (CSPs), based on native teicoplanin and teicoplanin aglycone, Chirobiotic T and Chirobiotic TAG, respectively, were evaluated for the high-performance liquid chromatographic separation of enantiomers of 15 unnatural conformationally constrained alpha-amino acids, Phe and Tyr analogs, and 12 beta-amino acids having cycloalkane or cycloalkene skeletons . The chromatographic results are given as the retention, separation and resolution factors along with the enantioselective free energy difference corresponding to the separation of the enantiomers . It is clearly established that in most cases the aglycone is responsible for the enantioseparation of amino acids . The difference in enantioselective free energy between the aglycone CSP and the teicoplanin CSP was between 0.02 and 0.30 kcal mol(-1) for these particular amino acids . The resolution factors are higher with the aglycone CSP . Although the sugar units generally decrease the resolution of amino acid enantiomers, they can contribute significantly to the resolution of some unusual amino acid analogs . By application of these two CSPs excellent resolutions were achieved for most of the investigated compounds by using reversed phase or polar organic mobile mode systems . The separation conditions were optimized by variation of the mobile phase composition.

Aesthetic Plast Surg, 2003 Jul-Aug, 27(4), 308 - 14
Comparison of the incidence and predicted risk of early surgical site infections after breast reduction; Kompatscher P et al.; In plastic surgery, clean, elective operations such as breast reductions are anticipated to have low risk factors for infections (1.1-2.1%) . To further lower or prevent surgical site infections (SSI), the efficacy of a prophylactic administration of anti-microbacterials remains a current controversial issue in plastic surgery . We report here the findings of a retrospective study in which we examined two groups of patients with breast reductions, one of which received a single-shot antimicrobacterial prophylaxis with cefuroxime preoperatively and the other who were given no anti-microbacterials . The aims were to determine the early SSI incidence of both groups, to classify breast reductions with respect to their inherent SSI risk by two widespread, combined risk scores, i.e., the National Nosocomial Infection Surveillance (NNIS) score and the Study on the Efficacy of Nosocomial Infection Control (SENIC) score, and to compare the actual SSI incidence to the predicted risk of the scores . In the divisions of plastic surgery at two hospitals, 153 patients (group I) and 136 patients (group II) could be included in the study in the 4-year period April 1997 to December 2001 . Excluded were all patients with unilateral breast reduction or breast reconstruction and patients who were followed up less than 30 days postoperatively . The two groups were comparable with respect to demographic and clinical features such as age and risk factors, and there were no detectable significant intergroup differences in the general perioperative data . According to the NNIS and the SENIC scores, all operations were "clean," and the American Society of Anesthesiologists (ASA) score was < 3 in all patients . Although the mean duration of the operation was significantly different in the two groups (190 min in group I, 160 min in group II; p < 0.001, Mann-Whitney test; 75th percentile at and 4 and 3 h, respectively), it was longer than 2 h in both groups . The incidence of early infections was 3.9% in the first group, compared with 3.6% in the second group (p = 1.0, odds ratio = 1.07, 95% CI = 0.32-3.6) . All infections were local and superficial; no general symptoms were noticed . Three patients had to be readmitted and two of these were reoperated . The rate of infections for both groups was higher than generally anticipated for this kind of clean operations and higher than predicted by the NNIS score for medium risk (predicted risk of 2.9%) . The reason for this discrepancy is that the NNIS score is an inpatient risk score which does not include a postdischarge SSI surveillance . Using the NNIS definition of SSI we would have had an infection rate of 0% in both groups in our study . According to the SENIC score, breast reductions can be classified also as medium risk of SSI with a predicted risk of 3.9%, which showed a nearly perfect correspondence with the actual SSI incidence in both study groups . The reason for this increased, medium risk is the factor "operation time > 2 h," which is obviously an inherent risk factor in breast reductions . Among the multitude of patient and nonpatient SSI risk factors, in healthy women operation time was the only factor which could be clearly identified.

Therapie, 2003 Nov-Dec, 58(6), 519 - 24
{Mucoregulators in acute bronchitis syndromes: focus on use by general practitioners and data from the literature}; Roche N et al.; Antibiotics have long been used in the initial treatment of acute bronchitis (AB) and acute exacerbations of chronic bronchitis (AECB) . However, their lack of value in AB has been clearly demonstrated and antibiotic therapy is justified in only a few cases of AECB . In parallel, although the value of mucoregulators in these diseases is still debated, their prescription remains important in general practice . In this context, our aim was to determine the prescribing behaviour of general practitioners (GPs) with regard to these drugs, as well as the beliefs of GPs concerning the place of mucoregulators in the treatment of AB in children and adult smokers, as well as in patients with non-obstructive AECB . A survey was carried out in 370 GPs, who were presented with three standardised and computerised medical cases: (i) rhinopharyngitis + AB in a child; (ii) AB in an adult smoker without a previous medical history; and (iii) a patient with non-obstructive AECB . The results showed that mucoregulators are frequently prescribed by GPs for children and adults with AB, or in AECB . This high prescribing rate is due to the belief of the GPs that these drugs are effective and well tolerated, which is confirmed by the literature . Their use avoids the frequent and unjustified prescription of antibiotics in situations where they are not recommended but where the patients request drug therapy.

J Clin Periodontol, 2004 Jan, 31(1), 68 - 74
Polymer-assisted regeneration therapy with Atrisorb barriers in human periodontal intrabony defects; Hou LT et al.; AIM: This study compared clinical results of 40 periodontal osseous defects treated by two types of absorbable barrier materials . MATERIAL AND METHODS: Thirty patients (23 males and seven females) suffering from moderate to advanced periodontitis (with comparable osseous defects) were randomly assigned to receive either Atrisorb barrier (n = 22; group A) or Resolut XT barrier (n = 18; group B) therapy . Periodontal phase I treatment and oral hygiene instruction were performed before periodontal surgery . Papillary preservation, partial thickness flap, citric acid root conditioning, and decortication procedures were applied during the operation . Bone defects were filled with demineralized freeze-dried bone allograft and minocycline mixture (4:1 ratio) . Postoperative care included 0.10% chlorhexidine rinse daily and antibiotic medication for 2 weeks . Clinical assessments including probing depth (PD), clinical attachment level (CAL), gingival recession (GR), plaque index (PII), gingival index (GI), and radiographic examinations were taken at the baseline, preoperatively and at 3 and 6 months after regenerative surgery . RESULTS: Six months following therapy, both Atrisorb and Resolut XT groups had achieved comparable clinical improvement in pocket reduction (3.9 versus 4.4 mm), attachment tissue gain (clinical attachment gain; 3.5 versus 3.6 mm), and reduction in the GI and in the PII . Within-group comparisons showed significant attachment gain and pocket reduction between baseline data and those at both 3 and 6 months postoperatively (p < 0.01) . There were no statistically significant differences in any measured data between groups A and B . CONCLUSIONS: The results of this study indicate that a comparable and favorable regeneration of periodontal defects can be achieved with both Atrisorb and Resolut XT barriers . Further long-term study and histologic observations of tissue healing are needed to evaluate whether Atrisorb is promising for clinical use.

Pract Midwife, 2004 Mar, 7(3), 17 - 21
Group B strep: prevention is better than cure; Plumb J et al.; We believe that the key issue for prevention of EOGBS infection is knowledge-if a pregnant woman knows she carries GBS, or has other risk factors present that increase the risk of her baby developing EOGBS infection, she can be offered IAP to protect her baby from this potentially devastating condition . Of course, women don't have to accept the recommended intravenous antibiotics in labour (or an ECM test, either privately or if available on the NHS) if they choose not to . But surely they should have access to good-quality information so they can make an informed choice about what is right for them and for their unborn baby? And midwives are in the perfect position to ensure that pregnant women have such information, resulting in appropriate treatment, which will minimise the number of babies suffering needlessly from EOGBS infection.

Acta Neurochir (Wien), 2004 Apr, 146(4), 355 - 61; discussion 361 Epub 2004 Feb 13.
Management of hardware infections following deep brain stimulation; Temel Y et al.; OBJECTIVE: To report our experience on hardware-related infections following deep brain stimulation (DBS) . METHODS: The present article presents the retrospective clinical notes review of gained in a two-centre, single-surgeon study experience of 108 consecutive DBS cases between 1996 and 2002 . In all patients the minimum follow-up was six months . One hundred and eight patients received an intracerebral electrode implantation and 106 underwent internalization . RESULTS: In total 178 electrodes were implanted with a mean follow-up of 42.6 months and a cumulative follow-up of 367.7 patient-years . Four patients (3.8%) developed an infection related to the DBS-hardware and all were initially treated with antibiotics . Two patients eventually required additional surgical treatment . CONCLUSION: Infections due to DBS-hardware can result in considerable levels of morbidity . In certain cases antibiotic therapy may be adequate . In others, surgical intervention to externalise the electrodes may be necessary . In our experience, there was never a need to remove the electrodes.

Clin Orthop, 2004 Mar, (420), 298 - 303
Volume and surface area study of tobramycin-polymethylmethacrylate beads; Seeley SK et al.; Polymethylmethacrylate bone cement beads impregnated with antibiotic are a common treatment for patients with persistent articular joint infections or osteomyelitis . They also are used as a prophylaxis for infection in patients with large soft tissue wounds . The current study was designed to evaluate the relationship between bead geometry and elution of the antibiotic tobramycin by methodically varying the shape of the beads for a given set of volumes . Beads of five shapes (spherical to ovoid) and two volumes were prepared and studied . Only 0.9% to 3.3% of the total amount of tobramycin present actually eluted from the beads in a 96-hour period and of this amount, approximately 1/3 eluted within the first 4 hours . The elution mass data indicate the benefit of numerous, small and elliptically shaped beads for maximal antibiotic availability . Additionally, a mathematical model is presented that describes these findings and can be used to predict tobramycin delivery rates from bone cement beads . This model assumes that the antibiotic is delivered through two mechanisms: fast dissolution of tobramycin initially adhering to the bead surface and slow release by diffusion through the polymer . The results generate diffusion coefficients for tobramycin in polymethylmethacrylate bone cement on the order of 2 x 10 cm/s.

Int J Clin Pract, 2004 Feb, 58(2), 210 - 3
First report of pulmonary Nocardia otitidiscaviarum infection in an immunocompetent patient from Turkey; Dikensoy O et al.; Nocardiosis is a rare disease, and worldwide, respiratory and disseminated infections are most often due to Nocardia asteroides which is recognised increasingly as an opportunistic infection in patients with underlying chronic debilitating disease or immunodeficiency . However, infection with N . otitidiscaviarum and pulmonary nocardiosis in an immune-competent host remains very rare . We report a 65-year-old immune-competent male with pulmonary N . otitidiscaviarum infection in whom complete cure was provided with a 6 months of antibiotic combination including trimethoprim-sulfomethaxazol . This is the first report of pulmonary N . otitidiscaviarum infection in an immune-competent patient from Turkey.

HNO, 2004 Apr, 52(4), 363 - 77; quiz 378
{The management of postintubation stenoses in children}; Schultz-Coulon HJ; Extubation difficulties after long-term endotracheal intubation in neonates and infants require immediate re-intubation with a somewhat thinner endotracheal tube, continuation of long-term intubation for another 7-14 days with antibiotic and antiphlogistic therapy including antireflux treatment as well as a subtile endoscopic examination . A tracheostomy is not indicated before several attempts of extubation have failed . An anterior cricoid split should be indicated with great care and in premature neonates only . In manifest cicatrical stenoses, subtile endoscopic diagnostics are an essential prerequisite for the choice of surgical method and time of surgery . In rather mild stenoses (grade II), laryngotracheal reconstruction (LTR) with anterior wall cartilage grafting is presently regarded as method of choice . For subglottic stenoses of higher degrees (grade III and IV), partial cricotracheal resection (PCTR) is felt to be the most successful procedure . For all scarred stenoses involving the glottic level, LTR with posterior and anterior wall cartilage grafting appears to be the only suitable treatment . LTR with anterior wall grafting only as well as the PCTR can be performed as a single stage procedure with postoperative long-term intubation on an intensive care unit for one or more days . LTR with posterior and anterior wall grafting requires long-term stenting for several weeks or months depending upon the individual condition . For long-term stenting, our so-called double-tube-technique using a modified Montgomery T silicon tube together with a perforated tracheal cannula has proved to be the safest and least irksome technique.

Anal Chem, 2004 Apr 1, 76(7), 2144 - 7
Fast screening of low molecular weight compounds by thin-layer chromatography and "on-spot" MALDI-TOF mass spectrometry; Santos LS et al.; Fast screening of low-MW compounds is performed by thin-layer chromatography (TLC) followed by direct on-spot matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identification with nearly "matrix-free" mass spectra using an UV-absorbing ionic liquid matrix . Owing to minimal background ions from the proton donor triethylamine/alpha-cyano-4-hydroxycinnamic acid ionic liquid matrix, three arborescidine alkaloids, the anesthesics levobupivacaine and mepivacaine, and the antibiotic tetracycline were readily characterized most frequently by the MS detection of their protonated molecules . The technique is fast and sensitive, requires little sample preparation and manipulation, and is therefore suitable for fast screening with TLC separation and MS identification of low-MW compounds, with potential applications in areas such as phytochemistry, synthetic chemistry, and product manufacturing quality monitoring.

Pneumonol Alergol Pol, 2003, 71(9-10), 449 - 57
{Pulmonary thromboembolism as a late complication of mitochondrial myopathy (Kearns-Sayer syndrome }; Fijolek J et al.; A case of pulmonary thromboembolism with transient pulmonary hypertension of a rare cause is presented . In 24-year-old woman myasthenia was recognised on the ground of ptosis and fixation of eyes muscles from the 14th year of age . The treatment with mestinon was ineffective . Before planned thymectomy serious disturbances of heart rhythm and conduction were confirmed . Stimulator was implanted and thymectomy was done . No improvement of neurological state was observed despite the treatment with mestinone and prednisone . When she was 30 years old disease of lung appeared with fever, cough and parenchymal and pleural lesions of right lung . Antibiotic therapy was ineffective . CT scan and US examination revealed large thrombus inside the right auricle connected with stimulator electrodes . Embolisation of right pulmonary arteria was confirmed also . Treatment with heparin was ineffective and thrombectomy was performed . Exact neurological examination stated that the patient had no typical symptoms of myasthenia and that symptoms related with eyes and heart could be result of mitochondrial myopathy . Diagnosis was confirmed by EMG examination and muscle biopsy.

J Postgrad Med, 2004 Jan-Mar, 50(1), 21 - 6
Invasive pulmonary aspergillosis: A study of 39 cases at autopsy; Vaideeswar P et al.; BACKGROUND: Aspergillus is a common cause of invasive mycosis, especially in immunocompromised or immunosuppressed individuals . AIMS: To study the incidence of invasive pulmonary aspergillosis and evaluate the predisposing factors and clinico-pathological manifestations . SETTINGS AND DESIGN: Retrospective analysis of autopsy material from a tertiary care hospital . MATERIAL AND METHODS: All autopsies performed over a 12-year period were reviewed and cases with invasive aspergillosis were analysed with respect to their clinical presentation, predisposing factors, gross and histological features, complications and causes of death . RESULTS: Among a total of 20475 autopsies performed in 12 years, 39 patients (0.19 %) had invasive pulmonary aspergillosis . There were 28 males and 11 females . Their ages ranged from five months to 67 years . Dyspnoea, fever, cough with mucopurulent expectoration, chest pain and haemoptysis were commonly encountered symptoms . Forty-one per cent of the patients had no respiratory symptoms . Fungal aetiology was not entertained clinically in any of the patients . The major underlying conditions were prolonged antibiotic therapy, steroid therapy, and renal transplantation, often associated with underlying lung diseases . Pneumonia, abscesses, vascular thrombosis and infarction were common findings at autopsy . Antecedent tuberculosis, mucormycosis, Pneumocystis carinii pneumonia and Cytomegalovirus infection were also present . In most cases, death was related to extensive pulmonary involvement or fungal dissemination . CONCLUSION: A diagnosis of invasive pulmonary aspergillosis should always be borne in mind whenever one is dealing with recalcitrant lung infections even with subtle immunosuppression . Radiological investigations and serologic markers can be utilised for confirmation and prompt therapy.

J Bone Joint Surg Br, 2004 Mar, 86(2), 269 - 75
The management of chronic osteomyelitis using the Lautenbach method; Hashmi MA et al.; We describe our medium-term results for the management of chronic osteomyelitis in long bones using the Lautenbach procedure . Seventeen consecutive patients (18 segments) were treated prospectively . Osteomyelitis had been present for a mean of 12.5 years (1 to 31) . A discharging sinus was present in all cases . Nine of the associated fractures had failed to unite and a further two needed correction of malunion . The Lautenbach procedure involves debridement, intramedullary reaming and the insertion of double-lumen tubes to establish both a local antibiotic delivery system and cavity analysis for volume and culture . The end-point of treatment is when the irrigate produces three consecutive clear cultures with improvement in the blood indices and obliteration of the cavity volume . The mean length of treatment was 27 days (14 to 48) . One patient required a second procedure and another local debridement for recurrence of the infection . Two patients had Papineau grafting because of cortical defects . All the patients have subsequently remained free from infection . After treatment 11 had internal or external fixation for treatment of non- or malunion or a joint replacement, including two successful limb-lengthening procedures . Two further patients, while cured of infection, underwent amputation for other reasons . The mean length of follow-up was 75 months . This procedure allows precise control over the osteomyelitis until objective assessment suggests that infection has been cleared and the cavity obliterated . We recommend this procedure for long-standing complex cases in which basic techniques using debridement and antibiotics have failed.

J Bone Joint Surg Br, 2004 Mar, 86(2), 212 - 6
Giant-cell tumour of bone . The long-term results of treatment by curettage and bone graft; Zhen W et al.; Giant-cell tumour of bone (GCT) is a locally benign aggressive tumour . The use of adjuvant agents, such as phenol or liquid nitrogen has been recommended to destroy the remaining tumour cells after curettage, and filling of the defect with methylmethacrylate cement has been advocated . Between 1957 and 1992 we treated 92 patients with a GCT with 50% aqueous zinc chloride solution and bone grafting . Their mean age at the time of surgery was 31 years (15 to 59) and the mean follow-up was 11 years (5 to 31) . Twelve (13%) had a local recurrence and one had a wound infection . Two developed degenerative changes around the knee . Eighty-six (93%) achieved good or excellent function . Three had moderate function, and three needed amputation . Our findings indicate that treatment with an aqueous solution of zinc chloride and reconstructive bone grafting after curettage gives good results.

South Med J, 2004 Mar, 97(3), 279 - 82; quiz 283
Epidural intracranial abscess as a complication of frontal sinusitis: case report and review of the literature; Fountas KN et al.; Two cases of epidural abscess as a complication of frontal sinusitis are presented . The diagnoses were suspected on the basis of history and were confirmed by magnetic resonance imaging and computed tomography . Both patients were treated successfully by means of surgery and intravenous antibiotics . One patient developed meningitis in the postoperative course and was treated by changing the antibiotic regimen . However, further follow-up in the outpatient clinic by physical examinations and brain computed tomography scans showed no longterm neurologic complications in either case . Intracranial suppuration, including epidural abscesses, can complicate acute and chronic frontal sinusitis . These complications are diagnosed by maintaining a high index of suspicion and using the appropriate neuroimaging studies without delay.

Anesth Analg, 2004 Apr, 98(4), 1124 - 6, table of contents
Prolonged cardiovascular collapse due to unrecognized latex anaphylaxis; Hebl JR et al.; We present a case of a prolonged anaphylactic reaction that occurred in temporal relationship to the administration of cefazolin . Subsequent allergy testing was positive for latex and negative for cefazolin-both unexpected results . Our case illustrates that medications administered before the onset of anaphylaxis should not be assumed to be the causative allergen and that a latex allergy should be considered in the differential diagnosis . Because the etiology of an anaphylactic reaction cannot be immediately determined, patients experiencing intraoperative cardiovascular collapse should be treated in a latex-free environment . IMPLICATIONS: We describe a patient who experienced latex-induced intraoperative anaphylaxis . The event coincided with antibiotic administration, which prompted us to erroneously assume that the causative allergen was medication related . Allergy to latex must always be considered as a potential culprit of perioperative cardiovascular collapse.

Prev Vet Med, 2004 Mar 16, 62(3), 153 - 63
Veterinary medicine protecting and promoting the public's health and well-being; Pappaioanou M; Dr . Calvin Schwabe's vision of "One Medicine" has long inspired many in the public health community to strive toward bringing human and veterinary medicine together to improve the public's health and well-being around the world . In an increasingly human-dominated world, as Dr . Schwabe suggested many years ago, human health provides the most-logical unifying or apical cause in veterinary medicine's hierarchy of values . Veterinarians in all aspects of the profession-have opportunity and responsibility to protect the health and well-being of people in all that they do, including protecting food security and safety; addressing threats to antibiotic sensitivity; preventing and controlling zoonotic emerging infectious diseases; protecting environments and ecosystems; participating in bio- and agro-terrorism preparedness and response; using their skills to confront non-zoonotic diseases (such as malaria, HIV/AIDS, vaccine preventable diseases, chronic diseases and injuries); strengthening the public-health infrastructure; and advancing medical science through research . This article provides an overview of contributions made by veterinarians in each of these areas, and discusses the challenges to be overcome and the need for strategic thinking and action to achieve the vision of "one medicine".

Pharmacotherapy, 2004 Mar, 24(3), 338 - 43
Macrolide therapy for Chlamydia pneumoniae in the secondary prevention of coronary artery disease: a meta-analysis of randomized controlled trials; Etminan M et al.; STUDY OBJECTIVE: As recent studies have shown that antibiotic therapy to eradicate Chlamydia pneumoniae may be beneficial in the secondary prevention of coronary artery disease, and studies to date may have lacked statistical power, we conducted a meta-analysis of randomized controlled trials to determine the role of antibiotic therapy in this patient population . DESIGN: Systematic review and meta-analysis of randomized controlled trials . PATIENTS: A total of 12,032 patients from nine studies . MEASUREMENTS AND MAIN RESULTS: We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and abstracts of conference proceedings to identify pertinent studies . The random effects model was used to estimate a pooled relative risk . Heterogeneity was assessed using the bootstrap version of the Q statistic with 1000 replications . In total, we reviewed nine randomized controlled trials enrolling 12,032 patients; six enrolled patients with acute coronary syndrome, two enrolled patients with stable coronary artery disease, and one enrolled a mixed population . Compared with placebo, macrolide therapy was not associated with a significant reduction in any coronary event (relative risk {RR} 0.98, 95% confidence interval {CI} 0.88-1.08), myocardial infarction or angina (RR 0.89, 95% CI 0.68-1.16), or overall mortality (RR 0.95, 95% CI 0.81-1.12) . CONCLUSION: Our results do not support routine use of antichlamydial therapy for secondary prevention of coronary events.

Mil Med, 2004 Feb, 169(2), 97 - 101
"Surgical research at the Uniformed Services University: one graduate's perspective--from student to Chief, Division of Surgical Research"; Burris DG et al.; In the 23 years since Dr . John Sharefkin presented his personal experience with Surgical Research at the Uniformed Services University, the opportunities offered have expanded . In addition, there have been many contributions to the surgical literature, including some leading to improved care of combat casualties . This article outlines how these opportunities have impacted the education of our students, the academic advancement of our active duty surgeons, and will offer benefit to our surgical patients of the future . USUHS is a unique resource for military medical research because its breadth of staffing and equipment and its neighbors make all these kinds of help and expertise available . It offers an opportunity for cooperation between military and civilian researchers of the kind that marked the great research success of WWII and radar, mass blood-banking, code breaking computers and antibiotic production.

Vnitr Lek, 2003 Dec, 49(12), 960 - 6
{Infectious and inflammatory factors in the etiology and pathogenesis of atherosclerosis}; Andel M et al.; Although the metabolic syndrome together with insulin resistance and their consequences are probably basic factors in pathogenesis of atherosclerosis, inflammatory and infectious aspects of this process are unquestionable only in some of the patients . Endothelial dysfunction was identified both in the experiment and in patients after herpes virus simplex 1 infection, cytomegaloviral infection, Chlamydia pneumoniae infection, or Helicobacter pylori infection . However, it is not clear whether it is always caused by direct specific activity of a given pathogen or whether it is a result of inflammatory cytokines activity, heat shock protein activity, or CRP activity . In recent years secondary antibiotic prevention in patients after myocardial infarction has been discussed . Lower mortality rate from acute myocardial infarction and cerebral vascular accidents were found in several observations of patients vaccinated against influenza . In patients with non-stable angina pectoris we have found significantly more frequent occurrence of IgG antibodies against Chlamydia pneumoniae . This occurrence was more frequent in diabetics compared to non-diabetics . Endothelia exposed to cyto-megaloviral infection exprimed adhesive molecules on their surfaces . After an increase of the concentration of glucose in medium to 11.0 mmol/l and 16.5 mmol/l the expression of adhesive molecules after cyto-megaloviral infection increased . Relationship of infection, inflammation, and atherosclerosis has been a subject of intensive investigation in recent years . Discussion of possible consequences of these findings, especially from viewpoint of atherosclerosis prevention and its organ complications, is of the same intensity . Hypothesis about participation of infection and inflammation in pathogenesis of atherosclerosis seems to be very attractive . In spite of the fact that findings supporting this hypothesis cumulate final conclusion can't be made yet.

Med Sci Monit, 2004 Apr, 10(4), PI55 - 64
Pharmacokinetics of erythrocyte-bound daunorubicin in patients with acute leukemia; Skorokhod OA et al.; BACKGROUND: The objective of the present study was in vitro and in vivo investigation of erythrocytes as vehicles for anthracycline antibiotics . MATERIAL/METHODS: The kinetics of daunorubicin binding with erythrocytes was studied in blood and in washed erythrocyte suspensions from healthy donors and patients with acute leukemia . The effect of daunorubicin on erythrocyte deformability was studied using cell filtration through membranes with 3 microm-diameter cylindrical pores . Erythrocyte-bound daunorubicin (EBD), prepared by equilibrating anticoagulated autologous blood with the antibiotic, was administered (45 or 60 mg/m2 body surface) to 14 leukemic patients as part of the 7+ 3 or RACOP courses . The pharmacokinetics of daunorubicin and its tolerability were studied . RESULTS: Human erythrocytes bound daunorubicin (rubomycin) in citrated whole blood or in washed saline suspension . The equilibrium erythrocyte/medium daunorubicin concentration ratios (attained in 30-60 min at 37 degrees C) averaged 2.9 +/- 0.5 (n=13) in blood and 5.7 +/- 0.6 (n=8) in suspension (p<0.001), without any significant difference between the erythrocytes of donors and patients with acute drug-resistant leukemia or leukemic relapses . Incubation of patient blood with daunorubicin (0.5 mg/ml cells) did not affect erythrocyte deformability (filterability) . After intravenous administration, the peak drug concentration and its elimination rate were lower for EBD than for free daunorubicin . The patients tolerated EBD better than its standard free form . In nine patients who received three EBD infusions, side effects were less frequent than in those treated with free daunorubicin . CONCLUSIONS: Our results indicate that daunorubicin-loaded erythrocytes are promising for clinical application and deserve further clinical study.

J Fr Ophtalmol, 2004 Mar, 27(3), 285 - 90
{Cat-scratch disease neuroretinitis}; Donnio A et al.; We report a case of cat-scratch disease neuroretinitis for which systemic and ocular investigations proved the responsibility of Bartonella henselae . An 11-year-old boy was referred to the hospital in November 2002 for severe visual loss in the left eye over the preceding 2 weeks . At the same time, he also developed a flu-like illness . The best corrected acuity in the left eye was counting fingers at 30 cm . Posterior segment examination on the left eye showed an optic disk edema with papillary and peripapillary hemorrhages and serous retinal detachment, mild vitreous inflammation, and two little perivascular white spots . The medical history was unremarkable except for a cat scratch on his left forearm 2 months before . Four weeks of antibiotic therapy including oral rifampin and doxycycline was used . Bartonella henselae immunoglobulin M were first detected with Bartonella henselae immunoglobulin G testing negative at this time . A 3-week serum showed immunoglobulin M seroreversion, while Bartonella henselae immunoglobulin G appeared . Other causes of optic disk edema with macular star were excluded by biological data . Bartonella antibodies to both Bartonella henselae and Bartonella clarridgeiae were detected in the cat . Ophthalmic follow-up showed progressive resorption of the neuroretinitis and the visual acuity increased to 5/10 . The significance of this case report lies in the reminder that this pathology can be the cause of neuroretinitis; the prognosis can be improved by earlier treatment.

Infect Immun, 2004 Apr, 72(4), 2222 - 8
Fc-dependent polyclonal antibodies and antibodies to outer membrane proteins A and B, but not to lipopolysaccharide, protect SCID mice against fatal Rickettsia conorii infection; Feng HM et al.; An emphasis on cellular immunity against Rickettsia has led to neglect of analysis of the role of antibody . The availability of an excellent mouse model of spotted fever rickettsiosis enabled investigation of a potential role of antibody in immunity to Rickettsia conorii . C3H severe combined immunodeficiency (SCID) mice were passively transfused with monoclonal antibodies against rickettsial outer membrane protein A (OmpA), OmpB, or lipopolysaccharide (LPS), polyclonal anti-R . conorii serum, Fab fragments of polyclonal antiserum, or no antibodies and then challenged 48 h later with 10 50% lethal doses (LD(50)) of R . conorii . All mice that received monoclonal antibodies against OmpA and two of four mice that received monoclonal antibodies against OmpB or polyclonal antisera were completely protected, but the recipients of anti-LPS antibodies or the Fab fragments were not protected . Polyclonal antibody treatment of C3H SCID mice that had been infected with 10 LD(50) of R . conorii 4 or 5 days earlier prolonged the life of the infected mice from 10.4 to 22.5 days and resulted in decreased levels of infectious rickettsiae in the spleen and liver 24 and 48 h later . Treatment with protective antibodies resulted in the development of large aggregates of R . conorii antigens in splenic macrophages and intraphagolysosomal rickettsial death and digestion . The kinetics of development of antibodies to R . conorii determined by immunoblotting revealed antibodies to LPS on day 6 and antibodies to OmpA and OmpB on day 12, when recovery from the infection had already occurred . Antibodies to particular epitopes of OmpA and OmpB may protect against reinfection, but they may not play a key role in immunity against primary infection . Antibodies might be useful for treating infections with antibiotic-resistant organisms, and some B-cell epitopes should be included in a subunit vaccine.

Int J STD AIDS, 2004 Mar, 15(3), 195 - 8
Management of sexually acquired reactive arthritis in 19 North Thames GUM clinics; Bell C et al.; Our objective was to describe how genitourinary medicine (GUM) clinics in the North Thames region manage sexually acquired reactive arthritis (SARA), and to compare management with national guidelines . A self-completed questionnaire survey and retrospective case note review was conducted between September and October 2001 . Clinicians in 33 clinics were asked to describe their clinic's policy on the management of SARA, and to review the last five cases seen or the last cases seen in the preceding two years, if less than five . Nineteen (58%) clinics took part . There were inter-clinic variations in the investigation and management of patients, with only 63% (12/19) of clinics offering non-steroidal anti-inflammatory drugs (NSAIDs) and 58% (11/19) giving doxycycline 1001mg . twice daily for two weeks for urethritis - the rest using any of three other antibiotic regimens . There was no consistent policy of referral between other specialties and GUM for genital screening and partner notification . A total of 36 male and female case notes were reviewed . Patients without arthritis or joint swelling (5/38, 13%), or with non-typical symptoms such as diarrhoea (5/38, 13%) were diagnosed inappropriately with SARA . Only 33 (87%) had evidence of a sexually transmitted infection (STI) with at least two (5%) of patients being treated with antibiotics despite no apparent indication being present . Only 21 (55%) had documented NSAID therapy . Case identification was difficult due to the lack of a national disease code (KC60) for SARA . The data suggest that a diagnosis of SARA is sometimes being made with no identifiable STI, or where symptoms are more suggestive that another route of infection is likely . A clear guideline within clinics to standardize prescribing of antibiotics is needed and collaborative policies with GUM are needed for other specialties to use when investigating and managing patients with seronegative arthritis . GUM should consider re-introducing a KC60 code for SARA for better case identification.

Dis Colon Rectum, 2004 May, 47(5), 704 - 10 Epub 2004 Mar 25.
Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: results of a randomized, controlled, clinical trial; La Torre F et al.; PURPOSE: The aim of this study was to evaluate if the combination of micronized purified flavonoid fraction with short-term routine antibiotic and anti-inflammatory therapy was better at reducing the intensity of postoperative symptoms and wound bleeding after a Milligan-Morgan's open hemorrhoidectomy than antibiotic and anti-inflammatory treatment alone . METHODS: Fifty patients were randomly assigned to receive routine antibiotic and anti-inflammatory treatment alone (control patients) or a combination of micronized purified flavonoid fraction with identical antibiotic and anti-inflammatory treatment (micronized purified flavonoid fraction patients) . The evolution of symptoms (pain, tenesmus, pruritus, and bleeding) during the postoperative period was assessed by means of patients' self-questionnaires . Each symptom was scored on a graded severity scale from 0 to 3, daily during the first three days of the immediate postoperative period, then at regular intervals (about every 14 days) until postoperative day 60 . A global score for evaluation of each postoperative symptom and bleeding was used . The global score for each symptom was the sum of scores for each patient over the study period . The global score for each symptom was compared between the two groups with the Mann-Whitney U test . RESULTS: No significant differences in age, gender distribution, and stage of disease between the two groups were noticed at baseline . Posthemorrhoidectomy symptoms were relieved more rapidly in the micronized purified flavonoid fraction group; during the first three postoperative days, the global score for each symptom was significantly more reduced in the micronized purified flavonoid fraction group . The global scores for each symptom are as follows: pain after 3 days, 6.16 (SD = 1.9) in the control group vs . 3.48 (SD = 1.8) in the micronized purified flavonoid fraction group (P < 0.0001); tenesmus, 5.36 (SD = 1.8) in the control group vs . 1.48 (SD = 1.5) in the micronized purified flavonoid fraction group (P < 0.0001); pruritus, 4.04 (SD = 1.9) in the control group vs . 1.84 (SD = 1.4) in the micronized purified flavonoid fraction group (P < 0.0001); bleeding, 4.4 (SD = 2.1) in the control group vs . 2.0 (SD = 1.3) in the micronized purified flavonoid fraction group (P < 0.0001) . A significant difference (P < 0.0001) between groups was also shown in favor of micronized purified flavonoid fraction patients when global scores were calculated over the entire study period (60 days) . CONCLUSION: Micronized purified flavonoid fraction used in combination with short-term antibiotic and anti-inflammatory treatment can reduce both the duration and extent of postoperative symptoms and wound bleeding following hemorrhoidectomy.

Ann Med Interne (Paris), 2003 Dec, 154(8), 515 - 21
{Progress in the management of pyogenic cerebral abscesses in non-immunocompromised patients}; Tourret J et al.; Advances in radiological techniques over the last two decades have enabled establishing well-defined clinical and radiological signs for the diagnosis of cerebral abscess . Conversely, no consensus has been reached on the appropriate therapeutic management . To date, there has been no published randomized therapeutic trial dedicated to cerebral abscesses, probably because of low incidence . Progress in bacterial epidemiology, imaging techniques allowing early diagnosis, and antibiotic therapy have however generated a shift towards more frequent use of shorter, exclusively medical, treatment . Based on a review of the literature, we present and discuss the treatments usually applied in specialized departments for non-immunocompromised patients.

Acta Paediatr Suppl, 2004 Feb, 93(444), 23 - 5
Nosocomial respiratory syncytial virus infection in neonatal units in the United Kingdom; Thwaites R et al.; Nosocomial Respiratory Syncytial Virus infections are frequently reported and tend to be more severe, because of comorbidity, such reports, however, are frequently from a single centre . The incidence and outcomes of nosocomial Respiratory Syncytial Virus infection in UK neonatal units over a five year period were estimated by interrogating the Capse Health Care Knowledge Systems database, which contains anonymised details of 55% of UK hospital admissions . A total of 79,642 admissions commenced on the infants' date of birth and contained an ICD-10 code for low birth weight or immaturity . Thirty-seven of the 79,642 admissions also contained a Respiratory Syncytial Virus code . Two (5.4%) with Respiratory Syncytial Virus and 2,736 (3.4%) without Respiratory Syncytial Virus died . Survivors with Respiratory Syncytial Virus codes experienced significantly increased length of stay . In the extreme immaturity sub-group the length of stay was 117.5 days with Respiratory Syncytial Virus and 51.3 days without Respiratory Syncytial Virus (p = 0.0002) . In the low birth weight or other preterm sub-group the length of stay with Respiratory Syncytial Virus was 69.2 and without Respiratory Syncytial Virus 14.7 days (p < 0.0001) . The observed low rate for nosocomial Respiratory Syncytial Virus (0.46/1000 admissions) should be regarded as a minimum . The increased length of stay in infants with Respiratory Syncytial Virus infection emphasises that units should have guidelines to prevent and deal with Respiratory Syncytial Virus outbreaks.

Infez Med, 1997, 5(3), 160 - 3
{Bacterial meningitis and CSF cytokines}; Ticca F et al.; Aim of study is the determination of concentrations of two important cytokines: TNF alfa and IL8 in children with bacterial meningitis to establish a correlation between infection, CSF concentration of cytokines and neurological sequelae . TNF alfa and IL8 concentrations in CSF have been measured by quantitative immunometric enzyme assay during the course of the disease . In the purulent meningitis we observed that CSF concentrations of these cytokines decreased to undectable values 24 to 48 hours after beginning of the antibiotic therapy . Conversely, in the 3 patients with mycobacterial meningitis (TBM) the concentrations of IL8 were higher for a longer period, being detectable in the CSF between 4 and 8 weeks after the beginning of the specific treatment . We found no significant differences of the values of IL8 in children with neurological sequelae compared with children without sequelae.

Pediatr Neurol, 2004 Mar, 30(3), 210 - 2
Misplaced peripherally inserted central catheter: an unusual cause of stroke; Parikh S et al.; Stroke in pediatric patients occurs with a frequency of 3 to 8 per 100,000 . The postevent evaluation attempts to identify the etiology of ischemia whether anatomic, hematologic, or embolic, with the intention of preventing future events . We present the case of a previously healthy male who developed unilateral facial and extremity weakness 2 weeks after receiving an appendectomy . Once the usual etiologies of stroke in pediatric patients were excluded, an evaluation of the peripheral venous catheter (placed for postoperative antibiotic delivery) demonstrated arterial misplacement . This article presents the first reported case of such an occurrence in the literature and exhibits the need to pursue all avenues of evaluation if the etiology of a pediatric stroke is not initially identified.

Arch Mal Coeur Vaiss, 2004 Feb, 97(2), 120 - 4
{Infectious endocarditis with negative blood cultures}; Omezzine-Letaief A et al.; Blood culture is a key investigation for the diagnosis of infectious endocarditis (IE) . When negative, there are diagnostic and therapeutic problems . The aim of this study was to determine the frequency, the clinical features and the aetiological factors of IE with negative blood cultures compared with IE with positive blood cultures compared with IE with positive blood cultures . The authors undertook a retrospective review of 98 cases of patients admitted for IE from 1991 to 2000 to the Department of Infectious Diseases and Cardiology of Sousse (Tunisia) . Of the 98 patients, 48 (48.9%), 29 men and 19 women with an average age of 34.3 years, had negative blood cultures . An infectious agent was identified in 7 cases (14.5%) by serology, valve culture or cerebrospinal fluid including Brucella (2), Coxiella (1) and Candida (1) . Therefore, in 41 cases (42%), the cause of IE was not determined . Transthoracic echocardiography was of diagnostic value in 96% of cases and transoesophageal echocardiography showed disease not observed on transthoracic echocardiography in 5 cases . The main complication was cardiac failure (27 cases) . The mortality was 14.5% . Comparison of the two groups showed that negative blood cultures were associated with a higher incidence of previous antibiotic therapy, extracardiac signs of IE and cardiac failure . Early surgical indications and mortality were the same in both groups . This report confirmed the high frequency of IE with negative blood cultures . Previous antibiotic therapy seems to be an important aetiological factor but cannot explain this high frequency . Methodological problems of blood cultures and the absence of systematic investigation for rare infectious agents are other possible factors.

No Shinkei Geka, 2004 Feb, 32(2), 127 - 33
{Pneumocystis carinii pneumonia complicating brain tumor}; Uzuka T et al.; Brain tumors are frequently treated with steroids due to the presence of peritumoral edema . However, in Japan it is not widely recognized that primary brain tumor patients who are receiving steroid therapy become susceptible to Pneumocystis carinii pneumonia (PCP) . We reviewed the clinical features and risk factors for PCP in brain tumor patients treated at our institution between 1994 and 2002 . The treated cases consisted of 6 men and 6 women ranging in age from 47 to 78 yr (mean age 65.3) . Underlying diseases included malignant glioma in 9 patients, malignant lymphoma in 2 patients and meningioma in one patient . All were diagnosed by respiratory disease specialists using bronchial washings and bronchoalveolar lavage or chest X ray/CT image . Radiation therapies were administered with 20 to 60 Gy (mean 52.9 Gy) except in one patient . Chemotherapy was performed with ranimustine in 4 malignant glioma patients and with methotrexate in 2 malignant lymphoma patients . Prednisone, begun perioperatively, was reduced gradually from a mean initial dosage of 38.3 mg/day orally . The duration of steroid treatment at the onset of PCP in these patients ranged from 41 to 79 days (mean 61.4 days) . Six patients (50%) died of PCP despite appropriate antibiotic therapy and 2 patients needed intensive therapy with a respirator . For early diagnosis of PCP, periodic serological (e.g.; the level of lactate dehydrogenase and beta-D-glucan) and radiological examination (e.g.; chest X ray and CT image) is indicated in patients with brain tumors, and prophylaxis against PCP might be needed for patients with intracranial neoplasms and who are also receiving high-dose and long-term steroid treatment.

Intern Med J, 2004 Mar, 34(3), 91 - 7
Community-acquired pneumonia: influence of management practices on length of hospital stay; Laing R et al.; AIMS: To identify variation in the management of -community-acquired pneumonia between two New Zealand hospitals and the factors that may account for any differences . METHODS: A 12-month, prospective two-centre study was conducted . Between July 1999 and July 2000, 474 adult patients with community-acquired pneumonia were enrolled: 304 in Christchurch Hospital and 170 in Waikato Hospital . The patients were similar in age, sex, prior antibiotic use and comorbidity . There was no significant difference in the clinical outcomes for the patients at the two centres . RESULTS: The mean duration of i.v . antibiotic therapy was 1.7 versus 3.0 days (P < 0.001) and length of stay (LOS) was 3.0 versus 5.9 days (P < 0.001) for Waikato and Christchurch Hospitals, respectively . Using multivariate analysis, we could account for 61% of the observed variation in LOS . Duration of i.v . antibiotic therapy independently accounted for 16% of variation in LOS compared with age (2%), chronic obstructive pulmonary disease, duration of fever, intensive care unit admission and centre of admission (all <1%) . For the duration of i.v . antibiotics, centre of admission, largely reflecting clinician practice at each centre, independently accounted for 13% of variation, compared with duration of fever (5%), admission to the Intensive Care Unit (4%), Pneumonia Severity Index score (3%) and bacteraemia (3%) . CONCLUSION: Of the identifiable factors, variations in clinician behaviour outweighed the influence of patient factors on the duration of i.v . antibiotic therapy, which in turn was the major determinant of LOS for patients hospitalised with community-acquired pneumonia . An early switch from i.v . to oral antibiotic therapy in conjunction with early discharge planning may significantly reduce LOS without compromising patient outcomes.

J Am Podiatr Med Assoc, 2004 Mar-Apr, 94(2), 126 - 34
Infection and fever in the elderly; Cristofaro PA; The elderly make more frequent use of general podiatric medical services than the younger population . It is therefore important for podiatric physicians to become familiar with the general principles of infectious disease as applied to an elderly population, which is susceptible to a wider spectrum of disease with more subtle and unusual clinical signs and symptoms . This article reviews the diagnosis and evaluation of suspected infection, appropriate laboratory testing, patterns of specific infectious disease syndromes, and antibiotic use in the elderly.

Surv Ophthalmol, 2004 Mar, 49 Suppl 2, S55 - 61
Reducing the risk of postoperative endophthalmitis; Olson RJ; Recent literature suggests that the incidence of postoperative endophthalmitis is variable and may be on the rise . This article reviews established perioperative preventative measures, and discusses some possible causes of postoperative endophthalmitis that may be insufficiently addressed by current risk reduction techniques . This article also considers future measures for reducing the risk of postoperative endophthalmitis.

Bioorg Med Chem, 2004 Apr 1, 12(7), 1585 - 604
Camptothecin: current perspectives; Thomas CJ et al.; This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic . Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials . Camptothecin possesses a novel mechanism of action involving the inhibition of DNA relaxation by DNA topoisomerase I, and more specifically the stabilization of a covalent binary complex formed between topoisomerase I and DNA . This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses . Modern synthetic approaches to camptothecin and several of the semi-synthetic methods are also discussed . Finally, a systematic evaluation of novel and important analogues of camptothecin and their contribution to the current structure-activity profile are considered.

Neurosurgery, 2004 Mar, 54(3), 599 - 603; discussion 603-4
Comparison of deep wound infection rates using a synthetic dural substitute (neuro-patch) or pericranium graft for dural closure: a clinical review of 1 year; Malliti M et al.; OBJECTIVE: The need to repair dural defects has prompted the use of dura mater substitutes . Many synthetic materials have been used for dural closure . Neuro-Patch (B . Braun Medical S.A., Boulogne, France) is a nonabsorbable microporous fleece composed of polyester urethane that has been approved for human use by the European Union since 1995 . To the best of our knowledge, no clinical series with Neuro-Patch have been published thus far, particularly with regard to septic complications . The aim of our study was to compare the safety of Neuro-Patch with that of pericranium graft with regard to postoperative wound infections . METHODS: This is a retrospective study of 1 year's experience including all patients who underwent dural plasty with a Neuro-Patch (n = 61) or pericranium graft (n = 63) . The follow-up period was at least 12 months after surgery . Before wound infection rates in the two groups were compared, factors suspected of being risks for neurosurgical site infection were evaluated . RESULTS: Patient characteristics (mean age, neurological diagnosis), surgical procedures, prophylactic antibiotics, and risk factors for surgical infections (including duration of surgery, emergency, contaminated operations, and external cerebrospinal fluid drainage) were similar in the Neuro-Patch and pericranium groups . Deep wound infection rates in the Neuro-Patch and pericranium groups were 15 and 5%, respectively (P = 0.06), and cerebrospinal fluid leaks were significantly more frequent in the Neuro-Patch group (13 versus 1.6%, P < 0.05) . CONCLUSION: The results of our investigations show that Neuro-Patch raised the risk of wound infection, as do foreign materials implanted in the body . Synthetic dural grafts should be reserved for when autologous grafts are not sufficient or possible . An extensive prospective multicenter randomized trial is needed to confirm our results.

Vet Surg, 2004 Mar-Apr, 33(2), 107 - 11
Treatment of septic common digital extensor tenosynovitis by complete resection in seven horses; Booth TM et al.; OBJECTIVE: To describe and evaluate a technique for radical resection of the entire intrathecal component of the common digital extensor tendon (CDET) in horses . STUDY DESIGN: Prospective clinical study . ANIMALS OR SAMPLE POPULATION: Seven client-owned horses . METHODS: Seven horses with wounds that resulted in septic tenosynovitis of the CDET sheath were treated by complete surgical resection of the affected tendon and ablation of the tendon sheath; 5 had previous surgery that was unsuccessful . Time from initial injury to complete resection was 1-22 weeks . In 6 horses, the wound was closed primarily using a closed suction (4 horses), penrose (1), or passive open drainage system (1) . In 1 horse, the surgical wound healed by second intention . All horses had postoperative bandaging, antibiotic administration, and physiotherapy . RESULTS: Surgical wounds healed primarily in 6 horses and by second intention in 1 horse . Follow-up (mean, 26.4 months; range, 18-38 months) was available for 6 horses; all returned to their athletic performance level without lameness or gait abnormality . CONCLUSIONS: Complete resection of the CDET was an effective surgical technique for management of chronic septic tenosynovitis . CLINICAL RELEVANCE: Horses with infection of the CDET and its sheath may be returned to long-term soundness without gait abnormality after radical resection.

Ann Dermatol Venereol, 2004 Feb, 131(2), 201 - 3
{Photochemotherapy for pityriasis lichenoides: 3 cases}; Panse I et al.; BACKGROUND: Pityriasis lichenoides is a rare cutaneous disorder of unknown origin that mainly affects children and young people . The disease consists of two variants: pityriasis lichenoides et varioliformis acuta, characterized by papular lesions evolving into necrosis and pityriasis lichenoides chronica characterized by scaly papules that may last from several months to several years . Various types of therapy have been proposed for pityriasis lichenoides, to our knockledge, photochemotherapy has never been used . We report the first 3 cases of pityriasis lichenoides treated by photochemotherapy . CASE REPORTS: Three patients, 6, 15 and 18 years old, presented respectively with a 1 month, 2 years and 3 months history of numerous, papular and necrotic lesions or squally papular lesions . Clinical appearance and histopathologic examination of biopsy were consistent with pityriasis lichenoides et varioliformis acuta (patients 1 and 3) and with pityriasis lichenoides chronica (patient 2) . They had received different treatments without significant effect: topical corticosteroids, antibiotic, UVB therapy and dapsone . Acitretin associated with PUVA were dramatically effective within few weeks . DISCUSSION: Pityriasis lichenoides can be a severe scarring disease with significant social, psychological and physical consequences . In our opinion, photochemotherapy, which has never been used in pityriasis lichenoides, is effective . Therapeutic modalities have to be define.

J Neuroradiol, 2004 Jan, 31(1), 69 - 71
Diffusion MRI findings in neonatal brain abscess; Sener RN; In neonates and infants, bacterial brain abscess is rare, and the diffusion weighted MR imaging appearance of such abscesses has not been reported . We report the diffusion weighted MR findings of a brain abscess in a 25-day-old boy . The lesion initially had a large cystic component with some high-signal pyogenic material inside on diffusion-weighted (b=1000 sec/mm(2))images . The ADC value of this material was low (0.59 x 10(-3) mm(2)/sec), compared to the value from normal cerebellar parenchyma (0.78 x 10(-3) mm(2)/sec) . The unusual initial appearance mimicked a cystic tumor . The lesion markedly decreased in size over 20 days after antibiotic therapy with persistent high-signal pyogenic material . In addition, at the initial presentation b=1000 sec/mm(2) images revealed high-signal changes in the brain parenchyma compressed by markedly dilated ventricles, consistent with ischemia . Also, ADC values of perilesional vasogenic edema (1.74 x 10(-3) mm(2)/sec), and that of transependymal resorption of CSF (1.56 x 10(-3) mm(2)/sec) were noted at the initial stage.

Drugs, 2004, 64(7), 679 - 92
Disseminated mycobacterium avium-intracellulare complex (MAC) infection in the era of effective antiretroviral therapy: is prophylaxis still indicated?
Lange CG, Woolley IJ, Brodt RH.
Before highly active antiretroviral therapies (HAART) were available for the treatment of persons with HIV infection, disseminated Mycobacterium avium-intracellulare complex (MAC) infection was one of the most common opportunistic infections that affected people living with AIDS . Routine use of chemoprophylaxis with a macrolide has been advocated in guidelines for the treatment of HIV-infected individuals if they have a circulating CD4+ cell count of < or =50 cells/microL . In addition, lifelong prophylaxis for disease recurrence has been recommended for those with a history of disseminated MAC infection.The introduction of HAART has resulted in a remarkable decline in the incidence of opportunistic infections and death among persons living with AIDS . Considerable reconstitution of functional immune responses against opportunistic infections can be achieved with HAART . In the case of infection with MAC, there has been a substantial reduction in the incidence of disseminated infections in the HAART era, even in countries where the use of MAC prophylaxis was never widely accepted . Moreover, the clinical picture of MAC infections in patients treated with potent antiretroviral therapies has shifted from a disseminated disease with bacteraemia to a localised infection, presenting most often with lymphadenopathy and osteomyelitis.Data from several recently conducted randomised, double-blind, placebo-controlled trials led to the current practice of discontinuing primary and secondary prophylaxis against disseminated MAC infections at stable CD4+ cell counts >100 cells/microL . These recommendations are still conservative as primary or secondary disseminated MAC infections are only rarely seen in patients who respond to HAART, despite treatment initiation at very low CD4+ cell counts.Potential adverse effects of macrolide therapy and drug interactions with antiretrovirals also metabolised via the cytochrome P450 enzyme system must be critically weighed against the marginal benefit that MAC prophylaxis may provide in addition to treatment with HAART . These authors feel that, unless patients who initiate HAART at low CD4+ cell counts do not respond to HIV-treatment, routine MAC prophylaxis should not be recommended . Nevertheless, the patient population for whom MAC prophylaxis may still be indicated in the era of HAART needs to be identified in prospectively designed clinical trials.

Novartis Found Symp, 2004, 257, 116 - 28; discussion 128-32, 157-60, 276-85
Fatal anaphylaxis in the UK, 1992-2001; Pumphrey RS; Each year in the UK, around nine deaths are attributed to anaphylaxis to pharmaceuticals, six to food and four to stings . I have identified 214 deaths associated with anaphylaxis, and have sufficient information for 196 to determine that 88 deaths were due to shock, 96 to asphyxia . Five deaths followed epinephrine overdose, seven were complicated by disseminated intravascular coagulation . There will have been other unrecognized fatal antibiotic and asthmatic food reactions . For foods, peak age was 17-27 with a female and atopic predominance; the first arrest was commonly from asthma 25-35 minutes after the implicated food . For stings, peak age was 45-70 with male and non-atopic predominance; death was commonly from shock 10-15 minutes after the sting . A majority of deaths from pharmaceuticals in hospital took 5 minutes or less from dose to arrest; peak age was 60-75 . Maximum time for any cause from trigger to first arrest was 6 hours . The danger of epinephrine overdose and its limitations in reversing anaphylaxis must be recognized . The patient should remain supine with legs raised throughout sting and other shock reactions . Prevention of fatal food reactions will depend on avoidance and optimal daily control of asthma.

Singapore Med J, 2003 Oct, 44(10), 531 - 5
Review of peripherally inserted central catheters in the Singapore acute-care hospital; Chlebicki MP et al.; Peripherally inserted central catheters are frequently used whenever reliable central venous access is required for a prolonged period of time . The objective of this study was to review utilisation profile, complication rates and outcomes of patients who were treated in our hospital with the therapy that required placement of the peripherally inserted central catheter . We reviewed the medical records of all patients who had peripherally inserted central catheter placed between the beginning of July and the end of October 2002 . Five patients who remained hospitalised at the time of review (six weeks after the last day of study period) were excluded . Seventy-eight patients with 94 peripherally inserted central catheters were analysed in detail . Sixty-four peripherally inserted central catheters (68.1%) were placed for prolonged antibiotic therapy, 27 (28.7%) mainly to administer total parenteral nutrition and 3 (3.2%) were inserted for other reasons . Catheters were in place before removal for a mean 17.2 days . Forty-eight catheters (51.1%) were removed after completion of therapy on average 20.2 days after insertion . Complications were frequent but minor . Thirty-three catheters (35.1%) were removed due to catheter-related complications . The most common complication were phlebitis followed by accidental removal . In summary, peripherally inserted central catheters proved to be reasonably safe and a reliable way of providing therapy requiring prolonged intravenous access . Complications were frequent but relatively minor . Complication rates in our study were similar to those reported in other studies on this subject . Peripherally inserted central catheters remain a convenient and reasonable alternative to other centrally or peripherally inserted venous devices.

Int J Syst Evol Microbiol, 2004 Mar, 54(Pt 2), 577 - 81
Streptomyces scabrisporus sp . nov; Ping X et al.; The taxonomic position was determined for a soil actinomycete, isolate KM-4927(T), that produced the antibiotic hitachimycin . The strain was assigned to the genus Streptomyces on the basis of 16S rDNA analysis, where it formed a separate clade . The strain is characterized by grey aerial cell mass, spiral spore chains and a rugose spore surface, menaquinones of the MK-9(H(4), H(2), H(6)) types and cell-wall chemotype I . DNA-DNA reassociation with 21 phylogenetically neighbouring Streptomyces type strains showing similar morphological characteristics to strain KM-4927(T) indicated that this isolate is only moderately related to other Streptomyces species . On the basis of genomic and physiological properties, the novel species Streptomyces scabrisporus sp . nov . is proposed; the type strain is strain KM-4927(T) (=JCM 11712(T)=NRRL B-24202(T)).

Arch Otolaryngol Head Neck Surg, 2004 Mar, 130(3), 329 - 33
Symptom outcomes after endoscopic sinus surgery for chronic rhinosinusitis; Bhattacharyya N; OBJECTIVE: To determine the effectiveness of endoscopic sinus surgery (ESS) for individual symptoms, medication use, and related factors in patients with chronic rhinosinusitis (CRS) . DESIGN: Nonrandomized, prospective, clinical trial . INTERVENTIONS: Adult patients with medically refractory CRS were examined before ESS with the Rhinosinusitis Symptom Inventory to catalog major and minor symptoms, medication use, physician visits, and missed workdays due to CRS . After a minimum 6-month follow-up after ESS, patients were examined to determine response to therapy . After computation of Rhinosinusitis Symptom Inventory domains, comparisons were conducted and effect sizes were computed for the change in symptoms after surgery . RESULTS: One hundred adults completed the examination, with a mean follow-up of 19.0 months . Before surgery, the mean major symptom scores ranged from 2.5 to 3.5 (Likert scale, from 0 {symptom absent} to 5 {maximum severity}) and the minor symptom scores ranged from 0.8 to 2.8 . After surgery, statistically significant decreases in major and minor symptoms were noted (P<.001 for all) . The largest effect sizes were noted for the decreases in facial pressure, congestion, nasal obstruction, rhinorrhea, and headache (absolute value of effect size >0.85 for all) . Similarly, large effect sizes were noted for decreases in symptoms in the nasal (-1.30), facial (-1.13), and total (-1.25) symptom domains of the Rhinosinusitis Symptom Inventory . Medication use actually increased for topical nasal corticosteroids, but decreased for prescription antihistamines . A mean reduction of 1.1 antibiotic courses (mean decrease of 2.3 weeks taking antibiotics) was noted after ESS . CONCLUSIONS: Endoscopic sinus surgery provides significant symptom relief for the nasal and facial symptoms associated with CRS . Patients will often still require topical nasal corticosteroids for the management of their CRS, but can expect decreases in antibiotic requirements after ESS.

Arch Otolaryngol Head Neck Surg, 2004 Mar, 130(3), 289 - 92
Complications of otitis media before placement of tympanostomy tubes in children; Kacmarynski DS et al.; OBJECTIVES: To report the incidence of short-term complications from otitis media in children before placement of tympanostomy tubes (TTs) and to compare children treated according to the Agency for Health Care Policy and Research guidelines with those who were treated earlier or later than recommended . DESIGN: Retrospective outcomes review . PATIENTS: Subjects were children aged 10 or younger who had TTs inserted at a tertiary care county hospital from January 1, 1999, to December 31, 2000 . Exclusion criteria included prior TT placement, any concurrent head and neck procedure, and craniofacial defects . INTERVENTION: Tympanostomy tube placement . MAIN OUTCOME MEASURES: Any occurrences of otorrhea, tympanic membrane perforation, tinnitus, antibiotic reactions, speech or language delay, febrile seizures, or meningitis before placement of TTs documented in the county hospital records were recorded as complications . Hearing loss was considered separately . RESULTS: Of 147 children who met our criteria, 81 (55.1%) had 1 or more complications from otitis media before placement of TTs . Fifty-five (37.4%) had 2 to 6 complications documented . Adverse reactions to antibiotics were the most common complication, reported in 34 (23.1%) . CONCLUSIONS: Most children in this county hospital experienced short-term complications of otitis media before receiving TTs . Even the children treated "on time" according to the guidelines from the Agency for Health Care Policy and Research experienced complications; however, adherence to the guidelines had no significant effect on complications.

Asia Pac J Clin Nutr . 2003;12 Suppl:S31.
Modern pork production - Balancing efficient growth and feed conversion with product quality requirements and consumer demands; Van Barneveld RJ; Background - Profitable pork production in an environment of increasing global competitiveness, diverse markets and heightened consumer awareness is an ongoing challenge . The modern pork producer needs to balance the use of emerging technologies and intensive farming practices, which have the potential to significantly decrease the cost of production, with specific market requirements for a quality product . Manipulation of fat content and distribution, nutritional enrichment of pork products, use of 'clean and green' feed ingredients, and hormone and antibiotic free production practices are high on the list of requirements of most markets as is the relative cost of Australian pork to imports and other meats . As some of these requirements are conflicting, modern pork producers must adopt some innovative nutritional and production strategies if they are to remain commercially viable . Review - In a modern Australian pig production system, a sale liveweight of 96 kg for the domestic market can be achieved in approximately 160 days with a feed conversion ratio of 2.60:1 . This level of efficiency has been achieved through intense genetic selection for fast growing, lean animals over the past 30 years, an advanced knowledge of the nutritional value of feed ingredients and the nutritional requirements of pigs, and sophisticated production tools including advanced growth simulation models such as AUSPIG . Consumer demands for reduced levels of fat in pork has contributed to this efficiency given the high energetic cost of fat deposition relative to lean meat deposition . The development of export markets for Australian pork in 1996 coupled with a concurrent increase in consumer awareness of food production has prompted a renewed focus on factors influencing pork product quality traits in addition to the cost of production, particularly manipulation of fat quality, fat composition and fat distribution . For example, higher levels of intramuscular fat or marbling in pork, largely influenced by genetics, can positively affect the juiciness, tenderness and flavour of pork . In addition, a focus on dietary fat sources for growing pigs has been shown to influence fat quality and composition . Restricting the level of dietary unsaturated fats can reduce the incidence of soft fat, and restricting the use of dietary fish oils to 0.5% for at least two weeks prior to slaughter will maintain the processing and keeping qualities of the pork . In contrast, modified forms of fishmeal as a dietary source of long chain n-3 PUFA can effectively be used to produce n-3 enriched pork, a factor with potential to greatly increase the attractiveness of pork to some markets . As well as manipulation of the fat attributes of pork, other nutritional strategies that have potential to improve the quality of pork products include enrichment using dietary supplements of minerals such as selenium and a reduced reliance on antibiotics through improved nutrition and herd health status . Conclusions - Modern pork production involves rapid responses to changing market demands . A major issue faced by Australian producers is the need balance product quality requirements with increased costs of production . This is further confounded by the fact that modern technologies such as immunocastration, and the use of porcine somatotropin and genetically modified feed ingredients, all of which could potentially further enhance product quality while offsetting some of the costs of production, are poorly accepted in the market place.

Arch Pediatr, 2003 Dec, 10 Suppl 5, 550s - 556s
{Visceral leishmaniasis: new drugs}; Minodier P et al.; The standard treatment of visceral leishmaniasis is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug . Moreover, antimony unresponsiveness is increasing, both in immunocompetent and in immunosuppressed patients . Amphotericin B is a polyene macrolide antibiotic that binds to sterols in cell membranes . It is the most active antileishmanial agent in use . Its infusion-related and renal toxicity may be reduced by lipid-based delivery . Liposomal amphotericin B (Ambisome) seems to be less toxic than other amphotericin B lipid formulations (Amphocil, Amphotec) . Optimal drug regimens of Ambisome vary from one geographical area to another . In the Mediterranean Basin, a total dose of 18 to 24 mg/kg is safe and effective . Shortening the duration of treatment without decreasing the total dose (i.e., 10 mg/kg/day for 2 days) seems promising to reduce the global cost of the therapy.

Pediatr Pulmonol, 2004 Apr, 37(4), 362 - 7
Survey of breast-feeding practices and outcomes in the cystic fibrosis population; Parker EM et al.; The aim of this study was to survey cystic fibrosis (CF) patients to determine the frequency of breast-feeding and its association with onset and severity of CF symptoms . Three thousand, two hundred questionnaires were sent to 30 accredited CF centers for anonymous completion . Eight hundred and sixty-three questionnaires were returned and scanned into a database . All results were adjusted for age at time of filling out the questionnaire . Age at onset of symptoms, percent forced expired volume in 1 sec (FEV1%) predicted, and intravenous (IV) antibiotic use were analyzed based on breast-feeding history . Approximately 49% of respondents received human breast milk at some time, but only 18% were exclusively breast-fed . Breast-feeding exclusively for greater than 6 months was associated with a decrease in disease severity based on recent intravenous antibiotic use compared to no breast-feeding (P = 0.03) . There was no statistically significant change in onset of symptoms in the setting of breast-feeding; however, a trend toward delayed onset was seen in those receiving human milk . Fifty-three percent of those who breast-fed exclusively > or = 6 months had FEV1% values > 90%, compared to 47% of those not breast-fed . This is a suggestive but not statistically significant difference . In conclusion, breast-feeding for > or = 6 months is associated with decreased use of intravenous antibiotics in the 2 years prior to administering the questionnaire . This survey indicates that breast-feeding is not harmful to children with CF, and may be beneficial .

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

Eur J Clin Pharmacol, 2004 Apr, 60(2), 127 - 34 Epub 2004 Mar 12.
Drug utilisation in outpatient children . A comparison among Tenerife, Valencia, and Barcelona (Spain), Toulouse (France), Sofia (Bulgaria), Bratislava (Slovakia) and Smolensk (Russia); Sanz E et al.; INTRODUCTION: Scarce information about comparative diagnostic and therapeutic patterns in paediatric outpatients of different countries is found in the literature . OBJECTIVE: To describe the similarities and differences observed in diagnosis and therapeutic patterns of paediatric patients of seven locations in different countries . DESIGN: Cross-sectional, prospective, international comparative, descriptive study . PATIENTS AND METHODS: A randomly selected sample of 12,264 paediatric outpatients seen in consultation rooms of urban and rural areas and attended by paediatricians or general practitioners of the participating locations . Data on patient demographic information, diagnosis and pharmacological treatment were collected using pre-designed forms . Diagnoses were coded using the ICD-9 and drugs according to the ATC classification . RESULTS: Among the ten most common diagnoses, upper respiratory tract infections are in the first position in all locations; asthma prevalence is highest in Tenerife (8.4%) . Tonsillitis, otitis, bronchitis and dermatological affections are the most common diagnoses in all locations . Pneumonia is only reported in Sofia (3.8%) and Smolensk (2.3%) . The average number of drugs prescribed per child varied from 1.3 in Barcelona to 2.9 in Smolensk . There are no great differences in the profile of pharmacological groups prescribed, but a considerable range of variations in antibiotic therapy is observed: prescription of cephalosporins is low in Smolensk (0.7%) and higher in the other locations, from 16.5% (Bratislava) to 28% (Tenerife) . Macrolides prescriptions range from 12.6% (Toulouse) to 24.7% (Smolensk), except in Sofia where they drop to 5.6% . Trimethoprim and its combinations are used in Smolensk (23.3%), Sofia (11.8%) and Bratislava (8.7%) . Check-up consultations are not recorded in Smolensk and Bratislava, whereas in Toulouse these visits account for 16.2% of all consultations and in the other locations the percentage varies from 6.1% (Tenerife) to 1.9% (Sofia) . Homeopathic treatments are registered only in Toulouse . CONCLUSION: Except in asthma prevalence, there are no great differences in diagnostic maps among locations . Significant variations in the number of drugs prescribed per child and antibiotic therapies are observed . Areas for improvement have been identified.

Ophthalmology, 2004 Feb, 111(2), 244 - 9
Risk factors for central serous chorioretinopathy: a case-control study; Haimovici R et al.; PURPOSE: To identify systemic factors associated with the development of central serous chorioretinopathy (CSCR) . DESIGN: Retrospective, case-control study . Participants and controls: 312 cases and 312 controls . RESULTS: By use of a multivariate analysis, the previously described risk factors, systemic steroid use (odds ratio {OR}, 37.1; 95% confidence interval {CI}, 6.2-221.8), and pregnancy (OR, 7.1; 95% CI, 1.0-50.7), were strongly associated with CSCR . Additional risk factors identified by this study include antibiotic use (OR, 6.2; 95% CI, 1.0-37.9), alcohol use (OR, 4.9; 95% CI, 1.5-16.3), untreated hypertension (OR, 3.3; 95% CI, 1.3-8.5), and allergic respiratory disease (OR, 2.5; 95% CI, 1.2-5.1) . CONCLUSIONS: A wide variety of systemic factors are associated with CSCR . Prospective studies are warranted to evaluate the nature and significance of these associations further.

Ophthalmology, 2004 Mar, 111(3), 585 - 9
Endoscopically assisted balloon dacryoplasty treatment of incomplete nasolacrimal duct obstruction; Couch SM et al.; PURPOSE: To report the success rate of endoscopically assisted balloon dacryoplasty (EADCP) for treatment of acquired incomplete nasolacrimal duct obstructions (NLDOs) . DESIGN: Retrospective, noncomparative case series . PARTICIPANTS: Records of patients treated for incomplete NLDOs with EADCP by one of the authors (WLW) were reviewed . Diagnosis of incomplete NLDO was based upon subjective complaints of tearing, dye disappearance testing, clinical evidence of epiphora, and nasolacrimal duct irrigation . Endoscopically assisted balloon dacryoplasty was performed for incomplete obstructions identified . METHODS: One hundred forty-two nasolacrimal systems in 103 patients with incomplete NLDOs underwent EADCP for treatment of incomplete obstructions . A 3x15-mm balloon was utilized in all procedures, with silicone lacrimal tubes placed in 131 systems . Patients received postoperative topical antibiotic-steroid drops for 2 weeks and a 1-week tapering dosage of systemic methylprednisolone . MAIN OUTCOME MEASURES: Patients were assessed at their last postoperative visit by nasolacrimal system irrigation, dye disappearance testing, and subjective complaints of epiphora . RESULTS: Eighty systems (56%) experienced complete resolution of symptoms after surgery . Forty-eight additional systems (34%) showed improvement but still experienced periodic epiphora . Fourteen systems (10%) showed no improvement . The average time before follow-up was 7.5 months . CONCLUSION: Endoscopically assisted balloon dacryoplasty as a treatment for incomplete NLDOs provides complete relief or substantial improvement in a significant percentage of patients . Nasal videoendoscopy adds significantly to the understanding of this procedure and its potential for success . Endoscopically assisted balloon dacryoplasty should be considered an appropriate treatment option for selected patients with incomplete NLDOs.

J Toxicol Sci, 2004 Feb, 29(1), 63 - 71
Comparative assessment of prurifloxacin, sparfloxacin, gatifloxacin and levofloxacin in the rabbit model of proarrhythmia; Akita M et al.; The administration of certain quinolone antibiotics has been associated with a prolongation of the QT interval on electrocardiogram, and in rare cases ventricular arrhythmias such as torsades de pointes . In this in vivo study using a rabbit arrhythmia model, we assessed the proarrhythmic effects and changes in the QT interval elicited by the administration of NM394 (UFX), an active metabolite of the new quinolone antibiotic prulifloxacin, and three representative quinolones, sparfloxacin (SPFX), gatifloxacin (GFLX) and levofloxacin (LVFX) . Chloralose-anesthetized rabbits were co-administered a continuous infusion of methoxamine (15 microg/kg/min) together with NaOH (vehicle, 0.2 mol/L), SPFX (2, 3, 4 mg/kg/min), GFLX (4 mg/kg/min), LVFX (4 mg/kg/min) or UFX (4 mg/kg/min) via the ear vein, and then the effects on electrocardiogram were examined . SPFX and GFLX both prolonged the QT and QTc intervals . GFLX also induced premature ventricular contractions in all 6 rabbits that received it, and subsequently it induced torsades de pointes (TdP) in 3 of the 6 rabbits . SPFX infused at the dose of 4 mg/ kg/min induced conduction blocks without inducing TdP, whereas that infused at the lower dose of 3 mg/ kg/min induced both conduction blocks and TdP . The infusions with LVFX and UFX did not elicit remarkable prolongations in the QT interval, and none of the animals infused with the agents developed arrhythmia . These findings suggested that LVFX and UFX were less potent than SPFX and GFLX in prolonging the QT interval and inducing life-threatening arrhythmias.

J Pediatr Surg, 2004 Mar, 39(3), 464 - 9; discussion 464-9
Delayed versus immediate surgery in acute appendicitis: do we need to operate during the night?
Yardeni D, Hirschl RB, Drongowski RA, Teitelbaum DH, Geiger JD, Coran AG.
BACKGROUND/PURPOSE: Over the last 4 years, the authors changed their management of acute nonperforated appendicitis from emergent surgery within the first 2 to 6 hours of admission to initiation of antibiotic therapy with operation within 24 hours of admission in those seen in the late evening or early morning . They examined, therefore, whether a delay in operation for acute appendicitis would affect outcome measures of patient morbidity and resource use . METHODS: The medical records of 126 patients with acute appendicitis occurring between 1998 and 2001 were retrospectively reviewed . Incidence of perforation at surgery, length of stay (LOS), hospital charges, operating time, and complications as a function of duration between emergency room (ER) triage and operation (ER-OR) or admission and operation (Admit-OR) were analyzed by Student's t test, and regression analysis with P less than.05 considered significant . RESULTS: Thirty-eight children (26%) were operated on within 6 hours of ER triage, whereas the remaining 88 children (74%) were operated on between 6 and 24 hours from ER triage . No significant difference was noted in perforation rate, LOS, costs, or operative time, nor were substantial changes in complications noted between those with an ER-OR < or =6 hours and greater than 6 hours . Likewise, no significant differences in these outcome measures were noted for Admit-OR greater than 6 when compared with < or =6 hours . Only costs with ER-OR greater than 12 hours and LOS with Admit-OR greater than 6 hours were significantly (without Bonferroni correction) different than < or = 6 hours . Multivariable linear regression analysis identified only LOS as a significant predictor of time to OR . CONCLUSIONS: In children with acute appendicitis, delaying surgery until the daytime hours did not significantly affect operating time, perforation rate, or complications . Delayed management allows greater efficiency and effective use of physician and hospital resources, including decreased resident involvement in operations during the night.

J Pediatr Surg, 2004 Mar, 39(3), 381 - 6
Does VATS provide optimal treatment of empyema in children? A systematic review; Gates RL et al.; PURPOSE: The surgical literature is replete with studies describing methods of treatment for pediatric empyema . The purpose of this report was to perform an evidence-based review of the literature to determine the most effective and appropriate treatment for empyema in infants and children . METHODS: The MEDLINE database was searched for English- and Spanish-language articles published from 1987 through 2002 on the treatment of thoracic empyema in children . Additional unpublished data were obtained by contacting individual study authors . There were no multiinstitutional prospective studies; all were retrospective, institutional series . A true meta-analysis could not be performed because of inherent institutional bias and variability in outcome measures among studies . A Kruskal-Wallis nonparametric test was used to compare methods detailed in the individual studies . RESULTS: Forty-four retrospective studies with a total of 1,369 patients were available for analysis . Four treatment strategies were compared: chest tube drainage alone (16 studies, 611 patients), chest tube drainage with fibrinolytic instillation (10 studies, 83 patients), thoracotomy (13 studies, 226 patients), and video-assisted thoracoscopic decortication (VATS; 22 studies, 449 patients) . Outcome measures common to the majority of studies included length of stay, fever duration, l of antibiotic therapy duration, and duration of chest tube drainage . Patients undergoing early VATS or thoracotomy had shorter length of stay (P =.003) . There was a trend for shorter duration of postoperative fever compared with chest tube alone or with fibrinolytic therapy, but this did not reach statistical significance (P =.055) . There was no statistical difference in chest tube duration between methods . There was no trend correlating antibiotic use with treatment methods, length of hospital stay, duration of fever, or length of chest tube requirement . CONCLUSIONS: Early VATS or thoracotomy leads to shorter hospitalization . The duration of chest tube placement and antibiotic use is variable and does not correlate with treatment method . A carefully designed, multiinstitutional, randomized study would lead to the development of evidence-based standards that may optimize the treatment of thoracic empyema in children.

Pharmacogenomics, 2004 Mar, 5(2), 181 - 202
Pharmacogenomics of proton pump inhibitors; Furuta T et al.; Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are metabolized by cytochrome P450 isoenzyme 2C19 (CYP2C19) in the liver . There are genetic differences that affect the activity of this enzyme . The genotypes of CYP2C19 are classified into three groups: homozygous extensive metabolizer (homEM), heterozygous extensive metabolizer (hetEM), and poor metabolizer (PM) . The pharmacokinetics and pharmacodynamics of PPIs differ among the different CYP2C19 genotype groups . Plasma PPI and intragastric pH levels during PPI treatment are the lowest in the homEM group and the highest in the PM group . These CYP2C19 genotype-dependent differences in pharmacokinetics and pharmacodynamics of PPIs are reflected in the cure rates for gastroesophageal reflux disease and Helicobacter pylori infection with PPI-based therapies . The CYP2C19 genotyping test is a useful tool for deciding on the optimal treatment regimen using a PPI, including a dual (PPI plus antibiotic) or a triple (PPI plus two antibiotics) therapy.

J Clin Periodontol, 2004 Apr, 31(4), 286 - 92
Comparison of the pharmacokinetic profiles of two locally administered doxycycline gels in crevicular fluid and saliva; Kim TS et al.; BACKGROUND: Controlled-release delivery systems enable the clinician to extend the half-life period of locally administered antibiotics in gingival crevicular fluid (GCF) significantly . The aim of this split-mouth study was to compare the pharmacokinetic profile of two different doxycycline gels (DOXY and ATRI) for topical subgingival application . Pharmacokinetics of both doxycycline gels were analyzed in GCF and saliva . METHODS: In 10 patients suffering from severe periodontitis, 10 pairs of contralateral defects (pocket depth > or =5 mm/bleeding on probing or > or =6 mm) were randomly assigned either to the first application of DOXY or ATRI . Fourteen days after the topical application of the first antibiotic gel, the application of the second gel in the contralateral defect took place . Clinical examinations at baseline showed no significant differences between sites treated with DOXY and ATRI . Samples of GCF and saliva were drawn baseline, 2, 5 and 24 h after application, 2, 3, 4, 7, 9 and 11 days after application . Separation and quantitative measurement of both doxycycline-gels was performed with HPLC- and UV-detection at lambda=260 nm . RESULTS: In saliva specimens, time-dependent changes of mean doxycycline concentration were almost identical for both doxycycline-gels and declined from a maximum 2 h after application (ATRI: 6653.90+/-3096.14 microg/ml; DOXY: 5386.60+/-1542.02 microg/ml {arithmetic mean+/-SEM}) to zero values 9 days after application . In crevicular fluid specimens, sites treated with ATRI exhibited a faster decrease of mean doxycycline concentration (1085.30, 264.00, 273.94, and 258.00 microg/ml measured 2, 5, 24, and 48 h after application) than sites treated with DOXY (1388.38, 1300.40, 803.73, and 235.10 microg/ml) . The faster decrease of ATRI compared with DOXY could not be proved to be statistically significantly different . CONCLUSIONS: Both doxycycline gels showed pharmacokinetics of controlled-release delivery systems.

J Antimicrob Chemother, 2004 Apr, 53(4), 675 - 7 Epub 2004 Mar 10.
Stability of benzylpenicillin during continuous home intravenous therapy; Vella-Brincat JW et al.; OBJECTIVES: The aim of this study was to investigate the temperature profile of home intravenous (iv) antibiotic reservoirs and the stability of 16 megaunits of benzylpenicillin sodium in 120 mL of sodium chloride 0.9% at constant and variable temperatures . METHODS: A Tinytag computerized thermometer recorded temperatures every minute in the home iv antibiotic reservoir pouches of nine patients over a 24 h period . Similar bags containing benzylpenicillin sodium (16 megaunits) were maintained either at a constant 36 degrees C, 26 degrees C or 21-22 degrees C or were worn in a pouch by five healthy volunteers for a 24 h period . Other bags were stored at 3-5 degrees C for 10 days . The bags were sampled at timed intervals and benzylpenicillin concentrations assayed by HPLC . RESULTS: Median temperatures recorded in the infusion bags worn by the nine patients were in the range 16.7-34.1 degrees C . For infusion bags maintained at 36 degrees C, 26 degrees C and 21-22 degrees C, the concentrations of benzylpenicillin dropped below 90% of the initial concentration at a mean time of 5 h 18 min, 12 h 54 min and 13 h 20 min, respectively, whereas for bags worn by the healthy volunteers the mean time for 10% loss of benzylpenicillin was 9 h 20 min . In contrast, at 3-5 degrees C, concentrations of benzylpenicillin only dropped below 90% of the initial concentration at 8 days . CONCLUSIONS: Significant temperature-dependent degradation of benzylpenicillin occurs during continuous home iv antibiotic programme infusions, which could result in loss of efficacy.

Chem Biol Interact, 2004 Mar 15, 147(2), 151 - 61
Biochemical background of toxic interaction between tiamulin and monensin; Szucs G et al.; Tiamulin, a diterpene antibiotic, is used for treatment of pulmonary and gastrointestinal infections in swine and poultry . Combined administration of tiamulin and ionophores (e.g . monensin) to farm animals may lead to intoxication manifested in severe clinical symptoms . Tiamulin metabolite complex with cytochrome P450 has been suggested to be the basis of drug-interactions . However, the formation of metabolic intermediate complex is questionable . The effect of tiamulin-treatment on cytochrome P450 activities was investigated in rats . Ethylmorphine and aminopyrine N-demethylation activities as well as monensin metabolism (O-demethylation) increased in liver microsomes of tiamulin-treated (200 mg/kg) animals . CYP3A1 induction caused by tiamulin was confirmed by the results of Western blot analysis . To test metabolic intermediate complex formation as a result of tiamulin treatment, cytochrome P450 activities were also determined in the presence of potassium ferricyanide . The findings together with those of in vitro complex formation suggested that formation of metabolic intermediate complexes of tiamulin with cytochrome P450 could be excluded . On the other hand, the results of inhibition studies showed significant decrease of ethylmorphine or aminopyrine as well as monensin demethylation in the presence of tiamulin . Our results proved that tiamulin has dual effect on cytochromes P450 . It is able to induce and directly inhibit CYP3A enzymes, which are predominantly responsible for monensin O-demethylation . The direct effect of tiamulin as an inhibitor might play a more important role in toxicity than its putative effect as a chemical inducer of CYP3A enzymes.

Surg Infect (Larchmt), 2003 Winter, 4(4), 345 - 54
Candidemia: the impact of antifungal prophylaxis in a surgical intensive care unit; Swoboda SM et al.; BACKGROUND: Candidemia is fourfold more common in 1990 compared to 1980 . In addition, a shift to non-albicans species has occurred in some institutions . Antifungal prophylaxis (AP) is effective in high-risk patients including critically ill surgical patients, but its use has been attributed to a resultant shift to non-albicans candida species . We hypothesized that the use of fluconazole prophylaxis would lead to a decreased incidence of candidemia but a possible increased incidence of resistant species of Candida, especially Candida glabrata (CG) . METHODS: From 1990 to 2002, all patients with candidemia (C) in the surgical intensive care unit (SICU) of a large tertiary care hospital were identified and reviewed retrospectively . Antifungal prophylaxis began in 2000 for high-risk patients . The periods were separated into PRE (1990-2000), and POST prophylaxis (2000-2002) . RESULTS: Excluding the year of the trial studying prophylaxis, (1998; five cases of C) a total of 83 patients developed candidemia: 69 PRE (83%) (1.94/1000 patient days) and 14 POST (17%) (0.76/1000 patient days) (OR 0.44; 95% CI 0.25, 0.78; p = 0.004) . In the PRE period C . albicans (45%) and CG (30%) were predominant, whereas in the POST period, CG (9/14, 64%) (p = 0.05), and C . albicans (3/14, 21%) were common . Non-albicans species were 38/69 (55%) PRE and 11/14 (79%) POST, p = 0.14 . Mortality in the group was 43/83 (52%) and did not differ PRE/POST or based on treatment . Predictors of SICU mortality (model r2 = 0.61) included hospital length of stay (LOS) (OR 1.14, CI 1.04, 1.25), fever (OR 51.2, CI 2.46, 1064), and broad-spectrum antibiotics (OR 69.7, CI 2.08, 2351), whereas post-transplantation status (OR 0.005, CI 0.00, 0.56), blood sugar <180 mg/dL (OR 0.03, CI 0.01, 0.81), and fungal prophylaxis (OR 0.03, CI 0.01, 0.58) were associated with a decreased risk of mortality . CONCLUSIONS: Unfortunately, the mortality of candidemia remains high in SICU patients (52%) . In the SICU, risk factors for candidemia and mortality are common . However, antifungal prophylaxis has significantly decreased the annual incidence of candidemia without a statistically significant shift to non-albicans pathogens.

Surg Infect (Larchmt), 2003 Winter, 4(4), 327 - 33
Monotherapy versus multi-drug therapy for the treatment of perforated appendicitis in children; Nadler EP et al.; BACKGROUND: Children with perforated appendicitis often have a prolonged hospital course complicated by surgical site or intra-abdominal infections . Treatment with multiple intravenous (IV) antibiotics after appendectomy has been the standard of care for these patients . We have recently adopted a protocol using piperacillin-tazobactam (PT) as a single agent in lieu of the standard multi-drug regimen (MD) . We hypothesized that PT would be as effective as MD in reducing postoperative complications and would result in decreased resource utilization . METHODS: We reviewed the medical records of all children admitted to our hospital between January 1, 1998 and December 31, 2001 with the diagnosis of perforated appendicitis . Patients who underwent operation within the first 24 h of admission were divided into two groups based on their antibiotic regimen: PT versus MD . Demographic data, duration of presenting symptoms, initial WBC, length of stay, and infectious complications were abstracted . Categorical data were compared using Chi square analysis; continuous variables were compared using Student's t-test when the data were normally distributed and the Mann-Whitney U test when the data were skewed . RESULTS: There was no difference between the PT (n = 51) and MD (n = 43) groups with respect to age, duration of presenting symptoms, initial WBC, or length of hospital stay . However, patients in the MD group had a significantly higher overall complication rate than those in the PT group (14/43 vs . 4/51, p = 0.002) . Antibiotic-related complications including surgical site infections, venous catheter-related infections, intra-abdominal abscesses, and drug reactions were also higher in the MD group (10/43 vs . 4/51, p = 0.04) . The outpatient charges for each patient based on an average of seven days of home antibiotics were $2,460 for the PT group and $4,349 for the MD group . CONCLUSIONS: Children with perforated appendicitis can be managed effectively with a single broad-spectrum antibiotic after appendectomy . Monotherapy is not only more efficacious than multi-drug therapy, but may be more cost effective . The use of monotherapy for children with perforated appendicitis after adequate source control should be considered the treatment of choice.

Annu Rev Phytopathol, 1997, 35, 87 - 109
White pine blister rust control in North America: a case history; Maloy OC; White pine blister rust was introduced into North America at the turn of the twentieth century, threatening valuable white pine resources . Measures to eliminate, contain, or control this disease constitute the most extensive forest disease control effort in time, money, men, and materiel in the history of US forestry . The major thrust was protection of pine stands by eliminating currant and gooseberry (ribes) alternate hosts from within and around these stands . Failures with ribes eradication resulted in application of antibiotic fungicides without adequate testing . These failures, coupled with lower dependence on white pines and reduced need for a large reserve of men for fire fighting, led to sudden termination of the program in 1967 . The chronology of events and interactions between agencies and personnel responsible for the program provide an interesting case history and, it is hoped, valuable lessons for the future.

Farm Hosp, 2004 Jan-Feb, 28(1), 29 - 35
{A pharmacoeconomic study of in-hospital treatment against community-acquired pneumonia}; Bermejo Vicedo T et al.; INTRODUCTION: A computer-driven unit-dose drug-dispensing system allows for improved knowledge on pharmaceutical costs per DRG and clinical department, between-hospital pharmacoeconomic studies to be carried out, as well as deviation analysis . METHODS: A retrospective, cost-minimization study was undertaken to both analyze and compare prescriptions for a number of antibiotics and bronchodilators, and their costs in both 89 and 90 DRGs, as well as their cost per hospital stay in patients admitted to the Internal Medicine Departments of two hospitals in Areas 6 (HUPH) and 9 (SVO) in CAM (Autonomous Community of Madrid) . A statistical analysis was performed using the Kolmogorov-Smirnov test, Student 's "t" test, Mann-Whitney test, and least squares method . RESULTS AND CONCLUSIONS: Patient samples are similar, with no significant differences existing in clinical status at admission or in cure percentage . Also, no significant differences exist in antibiotic use, except for clarithromycin and ceftriaxone, which were more commonly used at SVO (P = 0.001 and P = 0.003, respectively), and levofloxacin, which was more commonly prescribed at HUPH (P < 0.001) . For identical results measured by using the cure index and mean stay, the cost of antibiotic therapy was significantly higher at HUPH (113.57 euro) versus SVO (78.32 euro), which related to a wider use of levofloxacin; while no statistical relation to clinical status was found that warranted its choice . No differences were seen in bronchoinhaler use which, together with antibiotics, represent 82.6% of cost at HUPH and 72% at SVO.

Acta Med Croatica, 2003, 57(5), 369 - 72
{Leptospirosis and hemorrhagic fever with renal syndrome in northwestern Croatia}; Golubic D et al.; Leptospirosis is a worldwide spread zoonosis, therefore being also present in northwest Croatia . It has been recently discovered that hemorrhagic fever with renal syndrome (HFRS) is present throughout Croatia, not just in the previously well known epidemic foci . Because of the similar clinical presentation and epidemiology of the two diseases, it is important to know the exact etiology of the current disease . The aim of this study was to determine the presentation of HFRS in northwest Croatia and possible coinfection in patients with leptospirosis . PATIENTS AND METHODS: During the 1988-2000 period, 42 patients with leptospirosis from northwest Croatia were analyzed . Leptospiral infection was confirmed in all 42 patients by microagglutination test . Serology for hantaviruses was done by ELISA test in a few patients with leptospirosis and severe renal failure . RESULTS: In the majority of patients (37/42: 88%) acute renal failure was mild or moderate, with creatinine values below 500 mol/l . However, 12% of the patients developed severe acute renal failure, with creatinine values over 500 mol/l . The main therapeutic regime in all patients with leptospiral infection included body fluid replacement (electrolyte and glucose infusions) and antibiotic therapy . In patients with severe acute renal failure, it was necessary to introduce hemodialysis treatment . There was no fatal outcome in our patients . Over the last few years, antibody titers to hantaviruses were assessed by ELISA testing in five patients with leptospiral infection and severe form of acute renal failure, confirming HFRS persistence in northwest Croatia Testing for specific antibodies to hantaviruses has been suggested in all patients with leptospirosis and in whole Croatia, especially in northwest Croatia.

Drugs Today (Barc), 1998 May, 34(5), 431 - 46
Drug therapy of inflammatory bowel disease; Egan LJ et al.; The drugs that are effective in inflammatory bowel disease (IBD) act by inhibiting the chronic unregulated intestinal inflammation in these patients . The mainstays of the drug therapy of IBD are a variety of formulations of 5-aminosalicylic acid (5-ASA), the conventional and newer low bioavailability glucocorticoids, the nitroimidazole antibiotic metronidazole, and certain immunomodulating agents . Increased understanding of the mechanisms of inflammation in IBD has permitted the development of effective designer drugs . These agents are products of the biotechnology industry and include antibodies to tumor necrosis factor (TNF)-alpha, antisense oligonucleotides and recombinant human interleukin (IL)-10 . In addition, a number of other agents such as nicotine and n-3 fatty acids are useful in certain patients . This review first focuses on the pharmacology and mechanism of action of these drugs in IBD, followed by an approach to the treatment of patients with ulcerative colitis (UC) and Crohns disease (CD) . The recommendations consider type and activity of IBD and are based largely on data from controlled trials and systematic reviews in the IBD literature.

Int J Pharm, 2004 Apr 1, 273(1-2), 37 - 44
Effect of chitosan and of N-carboxymethylchitosan on intraocular penetration of topically applied ofloxacin; Di Colo G et al.; The effects of chitosan hydrochloride (Ch-HCl) and of N-carboxymethylchitosan (CMCh), formulated in ophthalmic solutions, on the ocular pharmacokinetics of ofloxacin were studied in rabbits . The carboxymethylation of a chitosan of high molecular mass (1460 kDa) and deacetylation degree (89.9%) introduced 0.84 N-carboxymethyl groups per repeating unit . Aqueous solutions containing 1% (w/v) of either polymer showed a pseudoplastic rheologic behaviour, and, when instilled in rabbit eyes, produced no irritation . The kinetics of drug disappearance from tear fluid and the profiles of drug concentration in the aqueous humour versus time were determined and interpreted in the light of a pharmacokinetic model and of drug-polymer binding . Ch-HCl significantly enhanced intraocular drug penetration with respect to an isoviscous drug solution containing poly(vinyl alcohol) and to commercial ofloxacin eyedrops . This effect, which resulted in about 190% increase of the peak concentration in the aqueous, was ascribed to an increased corneal permeability . The polyanionic CMCh failed to enhance intraocular drug penetration . It nevertheless increased precorneal drug retention in virtue of its viscosity and of ofloxacin binding . Consequently, the residence time at concentrations higher than the MIC90 and the bioavailability of the antibiotic in the aqueous were increased by about 150 and 240%, respectively, with respect to the reference vehicle.

Zhonghua Wai Ke Za Zhi, 2004 Jan 22, 42(2), 75 - 6
{Infection after cardiac transplantation: prevention and management}; Chen ZQ et al.; OBJECTIVE: To explore and sum up the characteristics of infection after cardiac transplantation and to discuss the prophylaxis and management . METHOD: From May 2000 to April 2003, 36 patients received orthotopic heart transplantation, the clinical data were observed and analyzed . RESULTS: Infection occurred in 2 (6%) cases, both belonged to lung infection caused by human cytomegalovirus . The 2 cases were cured by ganciclovir intravenously . CONCLUSION: Good prophylactic method may decrease post cardiac transplantation infection significantly . It is very important to early diagnose and treat infection.

Mol Microbiol, 2004 Mar, 51(6), 1615 - 28
SCP1, a 356,023 bp linear plasmid adapted to the ecology and developmental biology of its host, Streptomyces coelicolor A3(2); Bentley SD et al.; The sequencing of the entire genetic complement of Streptomyces coelicolor A3(2) has been completed with the determination of the 365,023 bp sequence of the linear plasmid SCP1 . Remarkably, the functional distribution of SCP1 genes somewhat resembles that of the chromosome: predicted gene products/functions include ECF sigma factors, antibiotic biosynthesis, a gamma-butyrolactone signalling system, members of the actinomycete-specific Wbl class of regulatory proteins and 14 secreted proteins . Some of these genes are among the 18 that contain a TTA codon, making them targets for the developmentally important tRNA encoded by the bldA gene . RNA analysis and gene fusions showed that one of the TTA-containing genes is part of a large bldA-dependent operon, the gene products of which include three proteins isolated from the spore surface by detergent washing (SapC, D and E), and several probable metabolic enzymes . SCP1 shows much evidence of recombinational interactions with other replicons and transposable elements during its history . For example, it has two sets of partitioning genes (which may explain why an integrated copy of SCP1 partially suppressed the defective partitioning of a parAB-deleted chromosome during sporulation) . SCP1 carries a cluster of probable transfer determinants and genes encoding likely DNA polymerase III subunits, but it lacks an obvious candidate gene for the terminal protein associated with its ends . This may be related to atypical features of its end sequences.

Pediatr Transplant, 2004 Feb, 8(1), 39 - 43
A single center clinical experience in intensive care management of 104 pediatric renal transplantations between 1998 and 2002; Pape L et al.; Only a few publications about the treatment in the intensive care unit (ICU) after pediatric renal transplantation have been published yet . As there are no guidelines, we hereby describe the results and recommendations of our transplant unit . A total of 104 renal transplantations have been performed in 96 children at our center since 1998 . The age of the children has ranged from 6 months to 18 yr and their body weight from 6 kg to 110 kg . A special fluid management was performed in order to avoid hypotension and hypoperfusion of the graft . Systolic arterial pressure was kept at elevated levels above 100 mmHg during the first day after transplantation . The children remained on the respirator for 4-8 h after transplantation . Anticoagulation was performed using low dose heparin because of the size mismatch of the anastomosed vessels . The mean time in the ICU for the pediatric patients aged <3 yr was 2 days and for children older than 3 yr was 1 day . The main complications after renal transplantation in the ICU were disorders of electrolytes, acute renal failure because of a non-functioning graft (12%), bleeding from the anastomoses (4%), arterial or venous thrombosis (1%), arterial hypertension and pulmonary edema, defined as radiographic evidence (1%) . In case of non-function peritoneal- or hemodialysis were performed in the ICU . Young children were more frequently affected than older children . From 1998-2002 one patient died during the ICU time . The 3 yr graft survival rate was 90% . To sum up, children undergoing renal transplantation should be treated in a specialized unit postoperatively to avoid early non-functioning of the graft and extrarenal complications . General guidelines for postoperative care should be established .

Infect Dis Clin North Am, 2003 Dec, 17(4), 697 - 705
Risk factors for pneumonia in the intubated patient; Diaz O et al.; The information gathered here helps to explain why risk factors in the development of VAP vary from series to series . It also explains why different investigators have found opposite effects when evaluating the antibiotics . Antibiotic therapy has a bimodal effect in the development of VAP . Antibiotics protect against pneumonia development within the first days of MV, especially against types caused by endogenous flora, but they are responsible for selection of a set of resistant pathogens that are associated with significant attributable mortality, such as P aeruginosa and MRSA . These observations suggest that risk factors vary depending on the exposure to risk (ie, length of stay or MV) . This variable should be considered when stratifying patients for risk factor analysis and also in the design of clinical trials for VAP prophylaxis.

Rev Prat, 2003 Dec 15, 53(19), 2101 - 7
{Febrile neutropenia}; Bally F et al.; Chemotherapy-related neutropenia is frequently complicated by infections . In granulocytopenic cancer patients, the early empiric administration of broad-spectrum antibiotics is the cornerstone of the management and has dramatically decreased the infection-related mortality . Several intravenous antibiotic regimens have been shown to be effective and well tolerated, especially monotherapies with broad-spectrum beta-lactams . The analysis of the outcome of febrile neutropenic patients has allowed the differentiation of those at high risk from those at low risk of infectious complications . In low risk patients, oral antibiotic regimens have been shown as effective as intravenous regimens . Running studies will allow to determine the advantages and limits of an outpatient management.

Expert Opin Biol Ther, 2004 Mar, 4(3), 337 - 48
Recent advances in the development of peptide nucleic acid as a gene-targeted drug; Marin VL et al.; Peptide nucleic acid (PNA) is a non-ionic mimic of DNA that binds to complementary DNA and RNA sequences with high affinity and selectivity . Targeting of single-stranded RNA leads to antisense effects, whereas PNAs directed toward double-stranded DNA exhibit antigene properties . Recent advances in cell uptake and in antisense and antigene effects in biological systems are summarised in this review . In addition to traditional targets, namely genomic DNA and messenger RNA, applications for PNA as a bacteriocidal antibiotic, for regulating splice site selection and as a telomerase inhibitor are described.

AIDS Patient Care STDS, 2004 Feb, 18(2), 99 - 107
HIV-related pneumonia care in older patients hospitalized in the early HAART era; Sureka A et al.; Age-related variations in care have been identified for HIV-associated Pneumocystis carinii pneumonia (PCP) in both the 1980s and 1990s . We evaluated if age-related variations affected all aspects of HIV-specific and non-HIV-specific care for HIV-infected individuals with PCP or community-acquired pneumonia (CAP), or whether age-related variations were primarily limited to HIV-specific aspects of care . Subjects were HIV-infected persons with PCP (n = 1855) or CAP (n = 1415) hospitalized in 8 cities from 1995 to 1997 . Nine percent of our study patients had received protease inhibitors and 39% had received any type of antiretroviral therapy prior to hospitalization . Data were abstracted from medical records and included severity of illness, HIV-specific aspects of care (initiation of PCP medications), general measures of care {initiation of CAP medications, intubation, and intensive care units (ICU)}, and inpatient mortality . Compared to younger patients, pneumonia patients 50 years of age or older were significantly more likely to: be severely ill (PCP, 20.4% vs . 10.4%; CAP, 27.5% vs . 14.9%; each p = 0.001), receive ICU care (PCP, 22.0% vs . 12.8%, p = 0.002; CAP: 15.1% vs . 9.4%; p = 0.02), and be intubated (PCP, 14.6% vs . 8.4%, p = 0.01; CAP, 9.9% vs . 5.6%, p = 0.03) . Compared to younger patients, older patients (>/=50 years) had similar rates of timely medications for CAP (48.5% vs . 50.8%) but had lower rates of receiving anti-PCP medications (85.8% vs . 92.9%, p = 0.002) . Differences by age in timely initiation of PCP medications, ICU use, and intubation were limited to the nonseverely ill patients . Older hospitalized patients were more likely to die (PCP, 18.3% vs . 10.4%; CAP, 13.4% vs . 8.5%; each p < 0.05) . After adjustment for disease severity and timeliness of antibiotic use, mortality rates were similar for both age groups . Physicians should develop strategies that increase awareness of the possibility of HIV infection in older individuals.

J Soc Biol, 2003, 197(4), 389 - 96
{Impact of mutation rate on the adaptation of gut bacteria}; Giraud A et al.; To study the role of mutator bacteria in the evolution of bacterial populations, we followed the impact of the mutation rate of Escherichia coli strains in the colonisation of the gut of axenic mice and the evolution of the mutation rate of bacterial populations living in the gut . We show that mutator bacteria have an advantage during the colonization . This adaptive advantage comes from their ability to generate adaptive mutations faster than wild type strains, mutations that allow their maintenance in the ecosystem . However, while mutator bacteria are becoming specialised to the environment they are living in, they accumulate mutations that may be deleterious or lethal in secondary environments . By following the evolution of the mutation rate of bacterial populations living in the gut of mice receiving antibiotics, we show that this therapy selects not only for antibiotic resistant mutants but also for mutator alleles that enhance mutation rates and are responsible for the appearance of the resistance . The costs of a high mutation rate, due to the accumulation of mutations, is seen in environments where changes are recurrent . In an ever-changing situation where every change is new, mutator bacteria might help the evolution of bacterial populations.

Radiologe . 2004 Mar 2; {Epub ahead of print}
{Imaging of bacterial infections of the sacroiliac joint}; Groves C et al.; Infection of the sacroiliac joint can be pyogenic or granulomatous and is usually unilateral . There are a number of predisposing conditions including drug abuse and intra articular steroid injection, but in 44% of cases, no definite predisposing factors can be identified . Considerable delay between presentation and diagnosis is recognized . The clinical picture may be non-specific and variable, and clinical suspicion may be low due to the relatively low incidence of the condition . This is compounded by difficulties in clinical examination of the SIJs . The diagnosis is based on a history suggestive of infection, clinical or radiographic localization to the SIJs, and a positive blood culture or joint aspirate.The pathology of pyogenic sacroiliitis is reviewed with respect to the anatomy of the SIJ, and the differential diagnoses considered . The imaging findings, and relative merits of all the modalities are discussed with particular consideration given to changes over the course of the disease . Imaging strategies are evaluated and proposed . As the commonest presenting symptom is low back pain, consideration should be given to the addition of a STIR sequence covering the SIJs on all routine lumbar spine MR examinations . MR imaging is the most sensitive and specific imaging modality, while CT-guided arthrocentesis improves diagnostic confidence . Tc(99)MDP blood pool imaging mirrors the clinical features of resolution, and scintigraphy may be the best method to monitor response to treatment . Targeted antibiotic therapy usually leads to a full recovery.A high incidence of clinical suspicion, with MR imaging at an early stage are the essential prerequisites to an accurate diagnosis of bacterial sacroiliitis.

Nat Struct Mol Biol, 2004 Apr, 11(4), 316 - 22 Epub 2004 Mar 07.
Streptomycin interferes with conformational coupling between codon recognition and GTPase activation on the ribosome; Gromadski KB et al.; Aminoacyl-tRNAs (aa-tRNAs) are selected by the ribosome through a kinetically controlled induced fit mechanism . Cognate codon recognition induces a conformational change in the decoding center and a domain closure of the 30S subunit . We studied how these global structural rearrangements are related to tRNA discrimination by using streptomycin to restrict the conformational flexibility of the 30S subunit . The antibiotic stabilized aa-tRNA on the ribosome both with a cognate and with a near-cognate codon in the A site . Streptomycin altered the rates of GTP hydrolysis by elongation factor Tu (EF-Tu) on cognate and near-cognate codons, resulting in almost identical rates of GTP hydrolysis and virtually complete loss of selectivity . These results indicate that movements within the 30S subunit at the streptomycin-binding site are essential for the coupling between base pair recognition and GTP hydrolysis, thus modulating the fidelity of aa-tRNA selection.

J Clin Microbiol, 2004 Mar, 42(3), 1236 - 42
Hairpin primers for simplified single-nucleotide polymorphism analysis of Mycobacterium tuberculosis and other organisms; Hazbon MH et al.; We describe a novel, simple, rapid, and highly sensitive method to detect single-nucleotide polymorphisms (SNPs) in Mycobacterium tuberculosis and other organisms . Amplification refractory mutation (ARMS) SNP assays were modified by converting the SNP-detecting linear primers in the ARMS assay to hairpin-shaped primers (HPs) through the addition of a 5' tail complementary to the 3' end of the linear primer . The improved ability of these primers to detect SNPs in M . tuberculosis was compared in a real-time PCR with SYBR-I green dye . Linear primers resulted in incorrect or indeterminate allele designation for 6 of the 13 SNP alleles tested in seven different SNP assays, while HPs determined the correct SNP in all cases . We compared the cycle threshold differences (DeltaC(t)) between the reactions containing primer-template matches and the reactions containing primer-template mismatches (where a larger DeltaC(t) indicates a more robust assay) . The use of HPs dramatically improved the mean DeltaC(t) values for the SNP assays (7.6 for linear primers and 11.2 for HPs) . We designed 98 different HP assays for SNPs previously associated with resistance to the antibiotic isoniazid to test the large-scale utility of the HP approach . Assay design was successful in 72.4%, 83.7%, 88.8%, and 92.9% of the assays after one to four rounds of assay design, respectively . HP SNP assays are simple, sensitive, robust, and inexpensive . These advantages favor the application of this technique for SNP assays of M . tuberculosis and other organisms.

Aquat Toxicol, 2004 Apr 14, 67(2), 195 - 202
Generation and partial characterization of a transformed cetacean cell line; Pine M et al.; A primary epithelial cell line, DK1, established from renal tissue of a spontaneously aborted female Atlantic bottlenose dolphin was transfected with linearized pSV3.neo, an SV40 virus-derived plasmid encoding large tumor antigen (Tag) . Transfected cells were grown in cetacean culture medium supplemented with 400 microg/ml geneticin (G418), and individual clones were selected using cloning rings . DKN1 was the first clone to be evaluated for future research use, and has been continuously cultured for 8 years . Intracellular cytokeratin and the expression of Tag were determined in DKN1, and cell growth was evaluated under different concentrations of l-glutamine, glutathione, and N-acetylcysteine . DKN1 cells did not require high levels of l-glutamine as previously reported for cetacean cells, and addition of antioxidants at the concentrations used in this study (2.0mM) decreased the rate of cell division . These data suggest strongly that these immortalized bottlenose dolphin epithelial cells have different levels of, and requirements for, glutathione than would be considered normal for terrestrial mammalian cells, do not require high levels of l-glutamine as previously suggested for dolphin cells, and exhibit decreased levels of cell growth and viability in high levels of the antioxidant GSH and its precursor, NAC.

J Hosp Infect, 2004 Mar, 56(3), 198 - 201
Cefuroxime, rifampicin and pulse lavage in decontamination of allograft bone; Hirn M et al.; The risk of bacterial infection through allogenic bone transplantation is one of the major problems facing tissue banks . Different screening methods and decontamination procedures are being used to achieve a safe surgical result . The purpose of this study was to investigate the contamination rate in fresh frozen bone allografts after treating them with different decontamination methods . The allografts were contaminated by rubbing on the operating theatre floor for 60 min, after which they were rinsed either with sterile physiological saline, cefuroxime or rifampicin solution or they were washed with low-pressure pulse lavage of sterile physiological saline . Our findings show that low-pressure pulse lavage with sterile saline solution is very effective in removing bacteria from bone allograft, when compared with the antibiotic solutions tested.

Biomacromolecules, 2004 Mar-Apr, 5(2), 389 - 96
Synthesis and characterization of a biotin-alginate conjugate and its application in a biosensor construction; Polyak B et al.; Biotin was covalently coupled with alginate in an aqueous-phase reaction by means of carbodiimide-mediated activation chemistry to provide a biotin-alginate conjugate for subsequent use in biosensor applications . The synthetic procedure was optimized with respect to pH of the reaction medium (pH 6.0), the degree of uronic acid activation (20%), and the order of addition of the reagents . The biotin-alginate conjugate was characterized by titration with 2-anilinonaphthalene-6-sulfonic acid (2,6-ANS), 4-hydroxyazobene-2'-carboxylic acid (HABA) and by an HPSEC-MALLS analytical method as well as by FTIR and 13C NMR spectroscopy . As a compromise between the need for a high percent of molar modification of the alginate, on one hand, and sufficient gelling capability, on the other hand, an optimal modification of 10-13% of biotin-alginate was used . The new biotin-alginate conjugate was used for the encapsulation of bioluminescent reporter cells into microspheres . A biosensor was prepared by conjugating these biotinylated alginate microspheres to the surface of a streptavidin-coated optical fiber, and the performance of the biosensor was demonstrated in the determination of the antibiotic, mitomycin C as a model toxin.

J Clin Periodontol, 2003 Dec, 30(12), 1053 - 60
Gingival crevicular fluid levels of aspartate amino transferase, sulfide ions and N-benzoyl-DL-arginine-2-naphthylamide in diabetic patients with chronic periodontitis; Yucekal-Tuncer B et al.; BACKGROUND: The aim of this study is to analyze the correlations between plaque index (PlI), gingival index (GI), probable pocket depth (PPD), clinical attachment level (CAL), aspartate aminotransferase (AST), N-benzoyl-DL-arginine-2-naphthylamide (BANA) and sulfide ion activity (SIA) of diabetic patients with chronic periodontitis with regard to disease activity detected by AST levels . MATERIAL AND METHODS: A total of 95 sites from eight diabetic patients with chronic periodontitis and 74 sites from eight systemically healthy patients with chronic periodontitis were enrolled in the study . The patients had no history of periodontal treatment or any antibiotic therapy during the last 6 months and were nonsmokers . All the sites selected for the study had a CAL of at least 2 mm . Gingival crevicular fluid volumes (GCFV) were measured in all sites . RESULTS: According to the result of AST analysis, 45 sites were AST positive and 50 were AST negative in the diabetic group and 36 sites were AST positive and 38 were AST negative in the control group . There was a significant correlation between BANA hydrolysis and PPD in both diabetic and control groups, but no correlation between PPD and AST levels . A significant correlation was observed between AST-positive sites and GI, but not between GI and BANA hydrolysis . In both groups, the correlation between SIA and BANA hydrolysis was significant, but no correlation was revealed between SIA and AST levels in either diabetic or control groups . CONCLUSION: The GCF metabolites had significant correlations with periodontally diseased sites in patients with chronic periodontitis, whether diabetic or systemically healthy, and may help to confirm clinical findings.

J Biol Chem, 2004 May 7, 279(19), 19457 - 63 Epub 2004 Mar 04.
Hsp90/p50cdc37 is required for mixed-lineage kinase (MLK) 3 signaling; Zhang H et al.; Mixed-lineage kinase 3 (MLK3) is a mitogen-activated protein kinase (MAPK) kinase kinase that activates MAPK pathways, including the c-Jun NH(2)-terminal kinase (JNK) and p38 pathways . MLK3 and its family members have been implicated in JNK-mediated apoptosis . A survey of human cell lines revealed high levels of MLK3 in breast cancer cells . To learn more about MLK3 regulation and its signaling pathways in breast cancer cells, we engineered the estrogen-responsive human breast cancer cell line, MCF-7, to stably, inducibly express FLAG epitope-tagged MLK3 . FLAG.MLK3 complexes were isolated by affinity purification, and associated proteins were identified by in-gel trypsin digestion followed by liquid chromatography/tandem mass spectrometry . Among the proteins identified were heat shock protein 90alpha,beta (Hsp90) and its kinase-specific co-chaperone p50(cdc37) . We show that endogenous MLK3 complexes with Hsp90 and p50(cdc37) . Further experiments demonstrate that MLK3 associates with Hsp90/p50(cdc37) through its catalytic domain in an activity-independent manner . Upon treatment of MCF-7 cells with geldanamycin, an ansamycin antibiotic that inhibits Hsp90 function, MLK3 levels decrease dramatically . Furthermore, tumor necrosis factor alpha-induced activation of MLK3 and JNK in MCF-7 cells is blocked by geldanamycin treatment . Our finding that geldanamycin treatment does not affect the cellular levels of the downstream signaling components, MAPK kinase 4, MAPK kinase 7, and JNK, suggests that Hsp90/p50(cdc37) regulates JNK signaling at the MAPK kinase kinase level . Previously identified Hsp90/p50(cdc37) clients include oncoprotein kinases and protein kinases that promote cellular proliferation and survival . Our findings reveal that Hsp90/p50(cdc37) also regulates protein kinases involved in apoptotic signaling.

Int J Cancer, 2004 May 1, 109(5), 643 - 52
Geldanamycin, an inhibitor of the chaperone activity of HSP90, induces MAPK-independent cell cycle arrest; Bedin M et al.; The effects of GA, an ansamycin antibiotic in development as a lead anticancer drug, were studied in mouse BP-A31 fibroblasts and in human cancer-derived cell lines . GA and related molecules act by inhibiting the chaperone function of the Hsp90 protein through competition for ATP binding . The antiproliferative effects of GA have been attributed to destabilization of the Raf-1 protein, one of the targets of Hsp90, and to the resulting inhibition of MAPK . Addition of GA to BP-A31 cells, synchronously progressing through the G(1) phase, inhibited Rb hyperphosphorylation and G(1)/S transition irrespective of the time of addition . The G(1) arrest was accompanied by a progressive decrease in Raf-1 content, especially of the phosphorylated form; however, GA caused only partial inhibition of MAPK phosphorylation . We show that GA triggers a rapid and marked decrease in the kinase activity of the cyclin E/cdk2 complex coupled with a decline in both total and cdk2-associated cyclin E . In transient transfection experiments, inhibition of cyclin E expression by GA was correlated with inhibition of the transcriptional activity of the cyclin E gene promoter . Inhibition of cdk4 activity by GA was observed 3 hr after addition of the drug to late G(1) cells but not after a short (1 hr) exposure, as revealed by the phosphorylation of Rb on the Ser(780) residue . In human cancer-derived cell lines expressing or not a functional Rb protein, GA blocked proliferation and inhibited the transcriptional activity of the cyclin E gene promoter . In these cell lines, the antiproliferative effect of GA was not limited to the G(1) phase, suggesting the existence of multiple cellular targets of the drug .

Expert Opin Biol Ther, 2004 Feb, 4(2), 233 - 41
Genetically recombinant antibodies: new therapeutics against candidiasis; Burnie J et al.; Historically, the therapy of serious fungal infection has been dominated by monotherapy with the polyene antibiotic amphotericin B . Clinical failures, side effects, the lack of alternatives and the toxicity of this drug have heightened the need to produce alternative therapies, which have included fluconazole, voriconazole and caspofungin . The observation that recovery from disseminated candidiasis was associated with an antibody response to the 47 kDa Candida heat-shock protein (HSP)90 homologue, coupled with the ability to sequence all the antibodies from patients who have recovered from the infection and to re-express the dominant ones as fragments in Escherichia coli, has opened the possibility of immunotherapy . The first recombinant antibody fragment, Mycograb (Neu Tec Pharma plc), against Candida HSP90 is now in clinical trials in patients with disseminated candidiasis in Europe and the US . Laboratory and early clinical data support the concept of synergy between Mycograb and amphotericin B . This should improve outcome and diminish the risk of resistance occurring to either drug, without an increase in toxicity, as this should be minimal in a human antibody fragment representing the natural antibody that a patient produces on recovery.

Pharmacol Res, 2004 May, 49(5), 493 - 9
Pharmacokinetic interactions between omeprazole/pantoprazole and clarithromycin in health volunteers; Calabresi L et al.; The association omeprazole/clarithromycin is of current wide use in the treatment of Helicobacter pylori associated gastroduodenal ulcer . This combination may result in increased levels of omeprazole with potential interactions with commonly associated drugs . Kinetic/metabolic changes occurring after omeprazole/clarithromycin were compared to those occurring after pantoprazole/clarithromycin in healthy volunteers . Eight healthy volunteers, all males, age 25-34 years, all EM for CYP2C19, participated in a randomized, double blind crossover study in two periods of 7 days, separated by a 14-day washout . In each treatment period, subjects took either omeprazole 20mg b.i.d . together with clarithromycin 500 mg b.i.d., or pantoprazole 40 mg b.i.d . with the same dose of the antibiotic . The pharmacokinetic parameters of omeprazole and pantoprazole were compared to those after intake of both agents alone . Kinetics of unchanged clarithromycin was evaluated at the end of the two periods . The mean value of the area under the plasma concentration versus time curve (AUC) of unchanged omeprazole increased almost two-fold after concomitant administration of clarithromycin; the average 5-OH-omeprazole AUC was instead significantly reduced by 42% . Omeprazole clearance and volume of distribution were reduced significantly by 75 and 56%, respectively, after administration of the drug with clarithromicyn . No significant changes of the kinetic of pantoprazole and metabolites were observed . Kinetics of clarithromycin did not differ after the two associated treatments . The administration of clarithromycin with two different proton pump inhibitors indicates that the antibiotic can markedly increase omeprazole, not pantoprazole, levels . This observation may result in a better therapeutic response to omeprazole, but it may also potentially affect either the metabolism of CYP3A4 substrates or interfere with the absorption of drugs requiring an intact gastric digestion system.

Expert Opin Pharmacother, 2004 Feb, 5(2), 369 - 77
Current treatment for primary ciliary dyskinesia conditions; Yoo Y et al.; Primary ciliary dyskinesia (PCD) is a heterogeneous group of conditions characterised by ultrastructural defects of the cilia, which result in impaired mucociliary clearance . Although the incidence of PCD is low, early recognition and prompt management are important in order to prevent unnecessary morbidity, the progression of bronchiectasis and the deterioration of lung function . As the underlying defect in PCD cannot be corrected, the mainstay of therapy remains effective clearance of airway secretions and antibiotic therapy of respiratory tract infections . This paper highlights new developments in the field that have implications for the future management of PCD . These include beta-adrenergic agonists, arginine, uridine-5'-triphosphate, hypertonic saline and recombinant human DNase . It is to be hoped that these treatment modalities will have a therapeutic role in PCD.

Microbiology, 2004 Mar, 150(Pt 3), 641 - 7
Identification of a topoisomerase IV in actinobacteria: purification and characterization of ParYR and GyrBR from the coumermycin A1 producer Streptomyces rishiriensis DSM 40489; Schmutz E et al.; The biosynthetic gene clusters of the gyrase inhibitors coumermycin A(1) and clorobiocin contain two different resistance genes (gyrB(R) and parY(R)) . Both genes code for B subunits of type II topoisomerases . The authors have now overexpressed and purified the encoded proteins, as well as the corresponding A subunits GyrA and ParX . Expression was carried out in Streptomyces lividans in the form of hexahistidine fusion proteins, allowing purification by nickel affinity chromatography . The complex of GyrA and GyrB(R) was found to catalyse ATP-dependent supercoiling of DNA, i.e . to function as a gyrase, whereas the complex of ParX and ParY(R) catalysed ATP-dependent decatenation and relaxation, i.e . the functions of topoisomerase IV (topo IV) . This is believed to represent the first topo IV identified in the class of actinobacteria, and the first demonstration of the formation of a topo IV as a resistance mechanism of an antibiotic producer.

Internist (Berl), 2004 Feb, 45(2), 211 - 5
{Malabsorption syndrome . Rare differential diagnosis in a young patient}; Bitzer M et al.; In a young female patient originally coming from Albany, immunoproliferative small intestinal disease (IPSID) could be diagnosed as a cause for severe maladsorption . Considering clinical and histological criteria an early disease stage of IPSID could be diagnosed . Under the continuous treatment of doxycycline for more than 3 1/2 years, all disease manifestations like watery diarrhea, vomiting, pain in the upper abdomen and loss of weight disappeared . After discontinuation of the antibiotic therapy the patient reached a sustained response.

Biochim Biophys Acta, 2004 Mar 2, 1688(2), 102 - 11
Tear lipocalin: potential for selective delivery of rifampin; Gasymov OK et al.; The potential of ligand binding proteins as drug carriers and delivery systems has recently sparked great interest . We investigated the potential of tear lipocalin (TL) to bind the antibiotic, rifampin, and the environmental conditions for controlled release . To determine if TL binds rifampin, gel filtration was used to isolate protein fractions of tears . Rifampin was detected by absorbance spectroscopy in the elution fractions containing TL . The bound complex of rifampin-TL generates optical activity at about 360 nm, indicating a unique conformation at the binding site . Rifampin has a higher affinity for TL (Kd=128 microM) than albumin . Rifampin is released from the TL calyx in acidic conditions and is displaced by palmitic acid . Autooxidation of free rifampin begins in minutes but is delayed by at least 3 h in the presence of TL . These properties are conducive to stabilization and delivery of rifampin to tubercles that are acidic and rich in fatty acids . These studies show the potential of TL as a carrier for rifampin with controlled release to a targeted environment.

Am Fam Physician, 2004 Feb 15, 69(4), 885 - 90
Poisoning, envenomation, and trauma from marine creatures; Perkins RA et al.; In the course of their clinical work or during leisure activity, family physicians occasionally may encounter patients with injuries from marine creatures . Poisoning, envenomation, and direct trauma are all possible in the marine environment . Ciguatera poisoning can result from ingestion of predatory fish that have accumulated biotoxins . Symptoms can be gastrointestinal or neurologic, or mixed . Management is mostly symptomatic . Scombroid poisoning results from ingestion of fish in which histamine-like substances have developed because of improper refrigeration . Gastrointestinal and systemic symptoms occur . Treatment is based on antihistamines . Envenomations from jellyfish in U.S . waters and the Caribbean are painful but rarely deadly . Household vinegar deactivates the nematocysts, and manual removal of tentacles is important . Treatment is symptomatic . Heat immersion may help with the pain . Stingrays cause localized damage and a typically severe envenomation . The venom is deactivated by heat . The stingray spine, including the venom gland, typically is difficult to remove from the victim, and radiographs may be necessary to localize the spine or fragment . Surgical debridement occasionally is needed . Direct trauma can result from contact with marine creatures . Hemorrhage and tissue damage occasionally are severe . Infections with organisms unique to the marine environment are possible; antibiotic choices are based on location and type of injury . Shark attacks, although rare, require immediate attention.

Aust Fam Physician, 2004 Jan-Feb, 33(1-2), 91 - 3
Acute bronchitis in Australian general practice . A prescription too far?
Stocks NP, McElroy H, Sayer GP, Duszynski K.
OBJECTIVE: To quantify how frequently general practitioners in Australia prescribe antibiotics for acute bronchitis, which antibiotics are used, and whether there are subgroups of patients who might benefit from their use . DESIGN AND SETTING: A retrospective descriptive study using 3 sets of data: Australian Sentinel Practice Research Network, the Bettering the Evaluation and Care of Health (BEACH) Program, and the General Practice Research Network (GPRN) . RESULTS: Over 50% of all patients with 'acute bronchitis' had either chest or one or more systemic signs on physical examination . The rate of antibiotic prescribing for acute bronchitis was 79.6% of acute bronchitis visits using BEACH data 2001-2002 and varied from 68.6 (95% CI: 62.8-74.5%) in 2001 to 78.7 (95% CI: 72.2-85.2%) in 1999 using GPRN data . Penicillins, followed by macrolides, were the most commonly prescribed antibiotics . DISCUSSION: Australian GPs frequently prescribe antibiotics for 'acute bronchitis' despite guidelines to the contrary . One reason may be that many patients present with chest or systemic signs.

J Inorg Biochem, 2004 Mar, 98(3), 534 - 46
Organometallic complexes with biological molecules . XVIII . Alkyltin(IV) cephalexinate complexes: synthesis, solid state and solution phase investigations; Di Stefano R et al.; Dialkyltin(IV) and trialkyltin(IV) complexes of the deacetoxycephalo-sporin-antibiotic cephalexin {7-(d-2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid} (Hceph) have been synthesized and investigated both in solid and solution phase . Analytical and thermogravimetric data supported the general formula Alk(2)SnOHceph(.)H(2)O and Alk(3)Snceph(.)H(2)O (Alk=Me, n-Bu), while structural information has been gained by FT-IR, (119)Sn Mossbauer and (1)H, (13)C, (119)Sn NMR data . In particular, IR results suggested polymeric structures both for Alk(2)SnOHceph(.)H(2)O and Alk(3)Snceph(.)H(2)O . Moreover, cephalexin appears to behave as monoanionic tridentate ligand coordinating the tin(IV) atom through ester-type carboxylate, as well as through beta-lactam carbonyl oxygen atoms and the amino nitrogen donor atoms in Alk(2)SnOHceph(.)H(2)O complexes . On the basis of (119)Sn Mossbauer spectroscopy it could be inferred that tin(IV) was hexacoordinated in such complexes in the solid state, showing skew trapezoidal configuration . As far as Alk(3)Sn(IV)ceph(.)H(2)O derivatives are concerned, cephalexin coordinated the Alk(3)Sn moiety through the carboxylate acting as a bridging bidentate monoanionic group . Again, (119)Sn Mossbauer spectroscopy led us to propose a trigonal configuration around the tin(IV) atom, with R(3)Sn equatorial disposition and bridging carboxylate oxygen atoms in the axial positions . The nature of the complexes in solution state was investigated by using (1)H, (13)C and (119)Sn NMR spectroscopy . Finally, the cytotoxic activity of organotin(IV) cephalexinate derivatives has been tested using two different chromosome-staining techniques Giemsa and CMA(3), towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia) . Colchicinized-like mitoses (c-mitoses) on slides obtained from animals exposed to organotin(IV) cephalexinate compounds, demonstrated the high mitotic spindle-inhibiting potentiality of these chemicals . Moreover, structural damages such as "chromosome achromatic lesions", "chromosome breakages" and "chromosome fragments" have been identified through a comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the organotin(IV) complexes.

FEMS Microbiol Lett, 2004 Feb 16, 231(2), 253 - 60
Insertion of an E . coli lacZ gene in Acetobacter xylinus for the production of cellulose in whey; Battad-Bernardo E et al.; A mini-Tn10:lacZ:kan was inserted into a wild-type strain of Acetobacter xylinus by random transposon mutagenesis, generating a lactose-utilising and cellulose-producing mutant strain designated ITz3 . Antibiotic selection plate assays and Southern hybridisation revealed that the lacZ gene was inserted once into the chromosome of strain ITz3 and was stably maintained in non-selective medium after more than 60 generations . The modified strain had, on the average, a 28-fold increase in cellulose production and a 160-fold increase in beta-galactosidase activity when grown in lactose medium . beta-Galactosidase activity is present in either lactose or sucrose medium indicating that the gene is constitutively expressed . Cellulose and beta-galactosidase production by the modified strain was also evaluated in pure and enriched whey substrates . Utilisation of lactose in whey substrate by ITz3 reached 17 g l(-1) after 4 days incubation.

Isr Med Assoc J, 2004 Feb, 6(2), 67 - 9
Systematic Inventive Thinking: a new tool for the analysis of complex problems in medical management; Heymann AD et al.; The complexity of medical problems is a well-recognized phenomenon . In the presence of economic and cultural restrictions, medical decision-making can be particularly challenging . This paper outlines a system of analysis and decision-making for solving such problems, and briefly describes a case study in which the method was used to analyze the case of antibiotic overprescribing in a large health maintenance organization . The purpose of the study was to determine if a technique for problem-solving in the field of engineering could be applied to the complex problems facing primary care . The method is designated Systematic Inventive Thinking and consists of a three-step procedure: problem reformulation, general search-strategy selection, and an application of idea-provoking techniques . The problem examined is the over-prescribing of antibiotics by general practitioners working in Maccabi Healthcare Services, an HMO serving one and a half million patients in Israel . The group of healthcare professionals involved in the discussions generated 117 ideas for improving antibiotic use . Six of these ideas were then implemented in a national campaign in the winter of 2000/1 and 2001/2 . During this period, a significant reduction in per-visit antibiotic purchasing was observed for influenza visits (from 79.2 per 1,000 to 58.1 per 1,000, P < 0.0001), but not for other categories of visits . The SIT methodology is a useful technique for problem-solving and idea generation within the medical framework.

Ear Nose Throat J, 2004 Jan, 83(1 Suppl), 5 - 8
The formation and management of middle ear granulation tissue in chronic ear disease; Roland PS; Granulation tissue is an important pathogenic feature of all types of chronic ear disease, and it can be controlled and treated with good aural toilet, appropriate antibiotic therapy, topical steroids, and chemical cautery or surgical debridement.

Clin Infect Dis, 2004 Mar 1, 38(5), 605 - 11 Epub 2004 Feb 17.
Abnormal radiological findings and a decreased carbon monoxide transfer factor can persist long after the acute phase of Legionella pneumophila pneumonia; Jonkers RE et al.; Pulmonary abnormalities may persist long after the acute phase of legionnaires disease (LD) . In a cohort of 122 survivors of an outbreak of LD, 57% were still experiencing an increased number of symptoms associated with dyspnea at a mean of 16 months after recovery from acute-phase LD . For 86 of these patients, additional evaluation involving high-resolution computed tomography (HRCT) of the lung revealed pulmonary abnormalities in 21 (24%); abnormal HRCT findings generally presented as discrete and multiple radiodensities . Residual pulmonary abnormalities were associated with a mean reduction of 20% in the gas transport capacity of the lung . This latter sign could not be used to explain the increased symptoms of dyspnea reported by patients . Receipt of mechanical ventilation during the acute phase of LD, delayed initiation of adequate antibiotic therapy, and chronic obstructive pulmonary disease were identified as risk factors for the persistence of lung abnormalities.

Org Biomol Chem, 2004 Mar 7, 2(5), 701 - 8 Epub 2004 Jan 29.
Synthesis of the 2,3,4-trisubstituted indole fragments of nosiheptide and glycothiohexide; Bentley DJ et al.; Two routes to the protected 4-hydroxymethyl-3-methylindole-2-carboxylate fragment 17 of the thiopeptide antibiotic nosiheptide are described starting from methyl 4-methylindole-2-carboxylate 11, itself prepared in two steps, or from 3-amino-4-chlorobenzoic acid 26 . The first route can be adapted to the synthesis of a fragment of the related antibiotic glycothiohexide-alpha, the 3,4-bis(hydroxymethyl)indole-2-carboxylate in which the two hydroxymethyl groups are differentiated as in indole 19 or the lactone 20.

Ann Emerg Med, 2004 Mar, 43(3), 333 - 8
Emergency department management of sexually transmitted infections in US adolescents: results from the National Hospital Ambulatory Medical Care Survey; Beckmann KR et al.; STUDY OBJECTIVE: Adolescents are at risk for developing a variety of sexually transmitted infections for many reasons . Many of these adolescents present to the emergency department (ED) for their care . We describe the management of adolescent sexually transmitted infections in US EDs . METHODS: Data were obtained from the 1992 to 1998 National Hospital Ambulatory Medical Care Survey . All visits by adolescents aged 12 to 19 years were identified by any International Classification of Diseases, Ninth Revision code related to sexually transmitted infections . Treatment was reviewed and compared with existing guidelines from the US Centers for Disease Control and Prevention (CDC) . Multivariate logistic regression was used to determine the independent association of each of the following variables on antibiotic prescribing rates: sex, race and ethnicity, hospital location, age, and insurance . RESULTS: Eighteen thousand nine hundred ninety-nine records that represented 70,693,603 adolescent visits to US EDs were identified during the 7-year study period, of which 351 records representing 1.2 million visits were for a sexually transmitted infection . Mean age was 17.1 years, and 92% were female patients . Overall, 80% of patients diagnosed with a sexually transmitted infection were treated (received antibiotics or were admitted to the hospital); 91% of patients had pelvic inflammatory disease and 71% of patients had other sexually transmitted infections . Eight percent of patients diagnosed with pelvic inflammatory disease were admitted to the hospital . However, treatment for female patients with pelvic inflammatory disease was fully compliant with CDC recommendations in only 35% of cases (95% confidence interval {CI} 19% to 45%) and partially compliant in another 45%; 20% (95% CI 12% to 31%) of patients received either no treatment or treatment not in accordance with guidelines . Male patients were more likely to be treated for sexually transmitted infection (adjusted odds ratio {OR} 6.3; 95% CI 1.0 to 38.7), and Hispanic patients were less likely (adjusted OR 0.3; 95% CI 0.1 to 0.9) to be treated . Age, insurance type, and hospital location were not a factor in receiving antibiotics . For female patients who had a sexually transmitted infection, only 43% had a pregnancy test done, and of all adolescents diagnosed with a sexually transmitted infection, only 1 (0.3%) had an HIV test performed . CONCLUSION: Significant numbers of adolescents sought care for sexually transmitted infections in US EDs . Evaluation and treatment of these adolescents is not optimal . Male patients are more likely to be treated for a sexually transmitted infection . Hispanic patients are less likely to be treated for a sexually transmitted infection . Pelvic inflammatory disease is not always treated with antibiotics, and few patients with pelvic inflammatory disease are admitted to the hospital . HIV testing was almost never done . Further study is necessary to explain these disparities and optimize care.

J Antimicrob Chemother, 2004 Apr, 53(4), 592 - 9 Epub 2004 Feb 25.
Comparison of tetracycline and tigecycline binding to ribosomes mapped by dimethylsulphate and drug-directed Fe2+ cleavage of 16S rRNA; Bauer G et al.; OBJECTIVES: The new antibiotic tigecycline (9-t-butylglycylamido-minocycline; GAR-936) overcomes most of the known tetracycline resistance mechanisms . Here we analyse its mode of antibiotic action by probing 70S ribosomes of Escherichia coli with dimethylsulphate (DMS) and Fe(2+)-mediated cleavage to identify binding sites of tetracycline and tigecycline . METHODS: Fe(2+)-mediated cleavage makes use of the ability of Fe2+ to replace the Mg2+ ion complexed with tetracyclines . After addition of H2O2, Fe2+ generates short-lived, highly reactive hydroxyl radicals that can cleave RNA close to the tetracycline binding sites . RESULTS: We identified three prominent Fe(2+)-mediated cleavage sites in helices 29 and 34, and in the internal loop of helix 31 of 16S rRNA in the presence of tetracycline or tigecycline . Qualitatively, these sites are modified identically by both antibiotics, but quantitative differences observed in the cleavage intensities indicate that the drugs bind in slightly different orientations . These results are supported by DMS modification, mutational analysis of 16S rRNA and structural modelling of tigecycline at a tetracycline-binding site in the 30S ribosomal subunit . CONCLUSIONS: Both derivatives bind to identical or overlapping sites and probably share the same mode of antibiotic action . The fact that tigecycline overcomes most of the known tetracycline resistance mechanisms is interpreted as a result of steric hindrance due to the large substituent at position 9.

Cytotherapy, 2004, 6(1), 7 - 14
Yield of human adipose-derived adult stem cells from liposuction aspirates; Aust L et al.; BACKGROUND: Primary cultures of isolated human adipose-derived adult stem (ADAS) cells are multipotent and differentiate in vitro along the adipocyte, chondrocyte, neuronal, osteoblast, and skeletal muscle pathways . METHODS: We examined the ADAS cell yield per unit volume of liposuction tissue, and their surface protein phenotype by flow cytometry . Adipogenesis was assessed by Oil Red O staining and ELISA analysis of leptin secretion . RESULTS: The donor population was 87.5% female (n=18) with a mean age (+/-SD) of 44+/-10 years and body mass index (BMI) of 24.9+/-2.7 . The mean cell yield was 404 000+/-206 000 cells per milliliter of lipoaspirate (n=18) . Linear regression analysis of the cells derived from the female donors demonstrated a significant negative correlation between the number of cells obtained per milliliter of lipoaspirate with the BMI but not the age of the donor . The undifferentiated ADAS cells were homogeneously positive for the cell-surface markers CD10, CD13, CD29, CD44, CD49e, CD59, CD90, and HLA-ABC, and homogeneously negative for the cell surface markers CD11b, CD45, and HLA-DR . The absence of the panhematopoietic marker, CD45, indicates that the ADAS cells do not derive from circulating BM hematopoietic stem cells . Adipocyte differentiation led to a 5.1-fold increase in Oil Red O staining, and a 196-fold increase in leptin secretion levels . Culture of the cells in the presence of antibiotic and fungizone did not alter the undifferentiated ADAS cell immunophenotype based on flow cytometry, or their adipocyte differentiation based on leptin secretion . DISCUSSION: The ability to isolate a consistently homogeneous population of undifferentiated adult stem cells from adipose tissue of multiple donors supports their potential utility in future tissue-engineering applications.

Biochim Biophys Acta, 2004 Feb 27, 1636(1), 22 - 8
Binding site for fungal beta-lactone hymeglusin on cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase; Tomoda H et al.; We studied the molecular mechanism through which the fungal beta-lactone, hymeglusin, potently and specifically inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase . {(14)C}Hymeglusin covalently bound to purified rat liver and to recombinant hamster cytosolic HMG-CoA synthases . The enzyme activity was completely inhibited at a binding ratio of 1.6-2.0 mol {(14)C}hymeglusin/mol HMG-CoA synthase . Incubating the enzyme with 2 mM iodoacetamide (IAA) or 2 mM N-ethylmaleimide (NEM) but not with 1.0 mM diisopropyl fluorophosphates (DFP) completely inhibited the binding, suggesting that hymeglusin binds to a Cys residue of HMG-CoA synthase . Recombinant hamster HMG-CoA synthase labeled with {(3)H}hymeglusin was digested with V8 protease, and the {(3)H}peptide was purified by high performance liquid chromatography (HPLC) . The sequence of the peptide was Ser-Gly-Asn-Thr-Asp-Ile-Glu-Gly-Ile-Asp-Thr-Thr-Asn-Ala-{(3)H}hymeglusyl Cys-Tyr-Gly-Gly-Thr-Ala-Ala-Val-Phe-Asn-Ala-Val-Asn-, which corresponds to the active site sequence (from Ser 115 to Asn 141) of hamster HMG-CoA synthase . These findings showed that hymeglusin inhibits hamster cytosolic HMG-CoA synthase by covalently modifying the active Cys 129 residue of the enzyme.

Med J Aust, 2004 Mar 1, 180(5), 216 - 9
Trends in childhood illness and treatment in Australian general practice, 1971-2001; Charles J et al.; OBJECTIVE: To determine changes in morbidity and management of disease in children in Australian general practice . DESIGN AND SETTING: A comparative study of general practice consultations in children under 15 years, using data from cross-sectional general practice surveys (1990-91 and 2000-01), and a descriptive comparison with a similar study from 1971 . MAIN OUTCOME MEASURES: Relative rates of management (rate/100 general practice encounters) of the most common children's problems and treatments . RESULTS: Problems with significantly higher management rates in 2000-01 compared with 1990-91 included vaccination (11.1 v 7.6 per 100 encounters in 1990-91) and contact/allergic dermatitis (3.1 v 2.5) . Those managed significantly less often in 2000-01 v 1990-91 included acute otitis media (7.7 v 9.4), asthma (5.4 v 8.8), tonsillitis (4.4 v 6.0), acute bronchitis (3.8 v 5.3) and gastroenteritis (1.7 v 2.7) . Asthma management rates rose from 2.4% of all problems managed in 1971 to 7.2% in 1990-91, then fell in 2000-01 to 4.6% . More frequent rates of counselling and advice in 2000-01 (28.4% of encounters v 22.9% in 1990-91) were associated with a decrease in rates of prescribing and supply of medication (56.6% of encounters v 64.3% in 1990-91) . Antibiotic prescribing declined significantly (from 33.8 per 100 encounters in 1990-91 to 25.2 in 2000-01), as did prescribing of respiratory medications (from 15.5 to 9.9 per 100 encounters), while prescribing of vaccines and systemic corticosteroids doubled (from 9.6 to 18.8 per 100 encounters, and from 0.6 to 1.2, respectively) . (All comparisons between 1990-91 and 2000-01 are significant at P < 0.01.) CONCLUSIONS: These findings point to the emergence of a generation of Australian children who are generally well vaccinated and are less likely to present to GPs with "traditional" childhood illnesses.

J Am Acad Nurse Pract, 2003 Dec, 15(12), 546 - 9
A review of Ludwig's angina for nurse practitioners; Winters S; PURPOSE: To discuss the causative factors, clinical course, and current treatment modalities for Ludwig's angina, a submandibular cellulitis, and to raise nurse practitioners' (NPs') awareness of this condition . DATA SOURCES: Recent clinical articles, research, case studies, and medical texts . CONCLUSIONS: Ludwig's angina may be fatal . Early diagnosis, aggressive antibiotic therapy, and management involving a multidisciplinary team approach are imperative for the patient to progress without complications . IMPLICATIONS FOR PRACTICE: Education and awareness are crucial for successful diagnosis of and management of treatment for Ludwig's angina . Although NPs have a limited role in the treatment of Ludwig's angina, their ability to recognize the signs and symptoms will prompt emergency care and treatment and facilitate better outcomes for their clients.

Tidsskr Nor Laegeforen, 2004 Feb 19, 124(4), 492 - 3
{Kingella kingae and osteoarticular infections in children}; Nordal E et al.; BACKGROUND: In septic arthritis and osteomyelitis in children, the infectious agent is frequently not identified because of failure in obtaining bacterial growth from blood culture or osteoarticular aspirations . MATERIAL AND METHODS: We report a case of septic arthritis caused by Kingella kingae in a two-year-old boy . On the basis of a PubMed literature search, we present an overview of osteoarticular infections with K kingae in childhood . RESULTS AND INTERPRETATION: Over the last ten years there has been an increasing number of reports on osteoarticular infection in children caused by K kingae . The clinical course is usually benign . Direct inoculation of osteoarticular specimens into blood culture bottles is important in order to enhance isolation of K kingae, as this organism will often fail to grow when plated directly on solid media . Improved culture methods and increased awareness are important in order to identify the organism and thus enable targeted antibiotic therapy.

Antimicrob Agents Chemother, 2004 Mar, 48(3), 867 - 72
Geldanamycin, a ligand of heat shock protein 90, inhibits the replication of herpes simplex virus type 1 in vitro; Li YH et al.; Geldanamycin (GA) is an antibiotic targeting the ADP/ATP binding site of heat shock protein 90 (Hsp90) . In screening for anti-herpes simplex virus type 1 (HSV-1) candidates, we found GA active against HSV-1 . HSV-1 replication in vitro was significantly inhibited by GA with an 50% inhibitory concentration of 0.093 microM and a concentration that inhibited cellular growth 50% in comparison with the results seen with untreated controls of 350 microM . The therapeutic index of GA was over 3700 (comparable to the results seen with acyclovir) . GA did not inhibit HSV-1 thymidine kinase . Cells infected with HSV-1 demonstrated cell cycle arrest at the G(1)/S transition; however, treatment with GA resulted in a cell cycle distribution pattern identical to that of untreated cells, indicating a restoration of cell growth in HSV-1-infected cells by GA treatment . Accordingly, HSV-1 DNA synthesis was suppressed in HSV-1(+) cells treated with GA . The antiviral mechanism of GA appears to be associated with Hsp90 inactivation and cell cycle restoration, which indicates that GA exhibits broad-spectrum antiviral activity . Indeed, GA exhibited activities in vitro against other viruses, including severe acute respiratory syndrome coronavirus . Since GA inhibits HSV-1 through a cellular mechanism unique among HSV-1 agents, we consider it a new candidate agent for HSV-1.

J Cell Biol, 2004 Mar 1, 164(5), 667 - 75 Epub 2004 Feb 23.
Dendritic cell aggresome-like induced structures are dedicated areas for ubiquitination and storage of newly synthesized defective proteins; Lelouard H et al.; In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control antigen processing and presentation . One of these mechanisms is the sorting of polyubiquitinated proteins in large cytosolic aggregates called dendritic cell aggresome-like induced structures (DALIS) . DALIS formation and maintenance are tightly linked to protein synthesis . Here, we took advantage of an antibody recognizing the antibiotic puromycin to follow the fate of improperly translated proteins, also called defective ribosomal products (DRiPs) . We demonstrate that DRiPs are rapidly stored and protected from degradation in DALIS . In addition, we show that DALIS contain the ubiquitin-activating enzyme E1, the ubiquitin-conjugating enzyme E225K, and the COOH terminus of Hsp70-interacting protein ubiquitin ligase . The accumulation of these enzymes in the central area of DALIS defines specific functional sites where initial DRiP incorporation and ubiquitination occur . Therefore, DCs are able to regulate DRiP degradation in response to pathogen-associated motifs, a capacity likely to be important for their immune functions.

Ann Fr Anesth Reanim, 2004 Feb, 23(1), 31 - 8
{Pyloric stenosis management in France in 1999: a postal survey}; Jacqmarcq O et al.; OBJECTIVE: The aim of this postal survey was to know how were treated infants with hypertrophic pyloric stenosis in France in 1999 . METHODS: A questionnaire was sent to all French members of the Association Des Anesthesistes Reanimateurs Pediatriques d'Expression Francaise (Adarpef) . RESULTS: Half the cases of pyloric stenosis treated in France in 1999 were related by the survey . Preoperative management was short lasting (24 h) while the advised guidelines regarding biologic criteria for operation were poorly followed . Nevertheless, crush induction was only performed in 80% . CONCLUSION: The management of infants with pyloric stenosis must be improved, at least to obtain the generalization of crush induction.

Atheroscler Suppl, 2003 Dec, 4(5), 3 - 9
The next step in cardiovascular protection; Cannon CP; While aggressive interventional therapy and anti-thrombotic therapy have revolutionized the management of acute coronary syndromes (ACS), defined as acute myocardial infarction (MI) or unstable angina (UA), long-term event rates remain high . Elevated lipids, inflammation and infection have each been implicated as additional mechanisms contributing to instability of vulnerable plaques . The new frontier in ACS management has focussed on treatment of these components of vascular disease . Preliminary trials have shown that early treatment with statins after ACS reduces coronary events but additional studies are needed to confirm this benefit . Furthermore, it is not clear what degree of low-density lipoprotein cholesterol (LDL-C) lowering is needed to stabilize the ACS patient . Chlamydia pneumoniae has been implicated in the development of coronary heart disease (CHD) but the results of preliminary trials investigating anti-chlamydial antibiotics have been inconsistent . Therefore, the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT TIMI 22) trial has been designed specifically to determine whether standard LDL-C reduction (with pravastatin 40 mg) provides a similar clinical benefit to more aggressive LDL-C reduction (with atorvastatin 80 mg) . In 4162 ACS patients over a 2-year period, this trial will also evaluate the long-term effect of the quinolone antibiotic, gatifloxacin, in reducing cardiovascular events.

J Laryngol Otol, 2004 Jan, 118(1), 50 - 3
Complicated otitis media caused by Fusobacterium necrophorum; Giridharan W et al.; Fusobacterium necrophorum is implicated as an aetiological agent in a variety of necrotic diseases, such as Lemierre's syndrome (LS) in humans . LS was initially described as septic thrombophlebitis of the internal jugular vein secondary to an acute oropharyngeal infection . Other primary sources of infection include parotitis, otitis media, sinusitis, odontogenic infection and mastoiditis . In the pre-antibiotic era LS carried a high mortality . This has been reduced as a result of the widespread use of antibiotics, but there is still a definite morbidity and mortality associated with infection with this virulent organism . We report three cases of complicated otitis media caused by Fusobacterium necrophorum . The patients were treated successively with intravenous metronidazole and surgery.

EMBO J, 2004 Mar 10, 23(5), 1008 - 1019 Epub 2004 Feb 19.
Domain movements of elongation factor eEF2 and the eukaryotic 80S ribosome facilitate tRNA translocation; Spahn CM et al.; An 11.7-A-resolution cryo-EM map of the yeast 80S.eEF2 complex in the presence of the antibiotic sordarin was interpreted in molecular terms, revealing large conformational changes within eEF2 and the 80S ribosome, including a rearrangement of the functionally important ribosomal intersubunit bridges . Sordarin positions domain III of eEF2 so that it can interact with the sarcin-ricin loop of 25S rRNA and protein rpS23 (S12p) . This particular conformation explains the inhibitory action of sordarin and suggests that eEF2 is stalled on the 80S ribosome in a conformation that has similarities with the GTPase activation state . A ratchet-like subunit rearrangement (RSR) occurs in the 80S.eEF2.sordarin complex that, in contrast to Escherichia coli 70S ribosomes, is also present in vacant 80S ribosomes . A model is suggested, according to which the RSR is part of a mechanism for moving the tRNAs during the translocation reaction.

Cancer Biol Ther, 2004 Apr, 3(4), 361 - 70 Epub 2004 Apr 03.
Targeting of radio-isotopes for cancer therapy; Milenic DE et al.; Treatment of patients with therapeutic monoclonal antibodies (mAbs) such as rituximab (Rituxan), an anti-CD20 mAb, or trastuzumab (Herceptin), an anti-HER2 mAb, have shown efficacy in clinical trials and have gained approval from the Food and Drug Administration (FDA) . Mylotarg, an anti-CD33 mAb conjugated with the antibiotic calicheamicin has proven efficacious in the treatment of patients with acute myeloid leukemia and has also received FDA approval . However, the use of radionuclides to either augment inherent activity or to exploit the specific targeting properties has been a major development in mAb therapeutics . Radionuclide- bearing mAbs have recently been approved by the FDA; Zevalin, an anti-CD20 mAb armed with (90)Y and Bexxar, an anti-CD20 mAb armed with (131)I . This overview presents some background and some of the strategies pertaining to radiolabeled monoclonal antibody therapies with a focus on experiences reported for radiolabeled mAbs as evaluated in clinical trials.

Filaria J . 2003 Oct 24;2 Suppl 1:S6.
Clinical picture and outcome of Serious Adverse Events in the treatment of Onchocerciasis; Awadzi K; Ivermectin (Mectizan(R)) is the only drug currently recommended for the treatment and control of onchocerciasis . Serious adverse events rarely occur during treatment, except in subjects heavily infected with Loa Loa . This review of drug-related serious adverse events in the treatment of onchocerciasis therefore revisited the pre-Mectizan(R) reference drugs, DEC and suramin, and other candidate drugs studied extensively for the treatment of human onchocerciasis . The benzimidazole carbamate derivatives and the antibiotic doxycycline were excluded, since no serious adverse events have been reported regarding their use . Using recommended definitions, serious adverse events reported or observed after the use of each drug were summarised, the level of attribution determined, and the results tabulated . Prominence was given to treatment-related deaths . The clinical picture of severe symptomatic postural hypotension is described and used to illustrate the difference between the severity and the seriousness of an adverse event . The epidemiology, management and outcome of serious adverse events are presented . The role of future research is discussed.

Salud Publica Mex, 2003, 45 Supp 5, S657 - 61
{Chlamydia trachomatis infection in women using 2 family planning clinics}; Canto-de Cetina T et al.; OBJECTIVE: To determine the prevalence of Chlamydia trachomatis in women attending two family planning clinics in Merida, Yucatan, Mexico . MATERIAL AND METHODS: From January to December 1998, a cross-sectional study was conducted in 1,100 sexually active women between 15 and 45 years of age . Study subjects had not received antibiotic therapy for at least one month prior to their visit to the clinic . Endocervical samples were taken for bacterial detection with the enzymatic Wellcozyme immunoassay method . Data were analyzed using the Epi-Info program . Statistical analysis was conducted using the chi-squared test and prevalence ratios . RESULTS: Seventy four women were positive to Chlamydia trachomatis (6.7%) . Almost 50% of those women were asymptomatic . No statistically significant differences were found between the group with Chlamydia and the group without it who had vulvar-vaginal symptoms . Cervical changes were more frequent in infected women . More positive cases of Chlamydia infection were found in oral contraceptive users (8.3%) than among non users (5.4%) . CONCLUSIONS: Study results confirm the high prevalence of asymptomatic infections and emphasize the importance of timely diagnosis to avoid infection sequelae . The English version of this paper is available at:http://www.insp.mx/salud/index.html.

Chem Commun (Camb), 2004 Mar 7, (5), 510 - 1 Epub 2004 Jan 27.
Total synthesis of (+)-belactosin A; Armstrong A et al.; A concise first total synthesis of the antitumour antibiotic belactosin A is reported, involving coupling of beta-lactone carboxylic acid 3 with N-Ala-aminocyclopropyl alanine 11.

J Bacteriol, 2004 Mar, 186(5), 1362 - 73
In silico and transcriptional analysis of carbohydrate uptake systems of Streptomyces coelicolor A3(2); Bertram R et al.; Streptomyces coelicolor is the prototype for the investigation of antibiotic-producing and differentiating actinomycetes . As soil bacteria, streptomycetes can metabolize a wide variety of carbon sources and are hence vested with various specific permeases . Their activity and regulation substantially determine the nutritional state of the cell and, therefore, influence morphogenesis and antibiotic production . We have surveyed the genome of S . coelicolor A3(2) to provide a thorough description of the carbohydrate uptake systems . Among 81 ATP-binding cassette (ABC) permeases that are present in the genome, we found 45 to encode a putative solute binding protein, an essential feature for carbohydrate permease function . Similarity analysis allowed the prediction of putative ABC systems for transport of cellobiose and cellotriose, alpha-glucosides, lactose, maltose, maltodextrins, ribose, sugar alcohols, xylose, and beta-xylosides . A novel putative bifunctional protein composed of a substrate binding and a membrane-spanning moiety is likely to account for ribose or ribonucleoside uptake . Glucose may be incorporated by a proton-driven symporter of the major facilitator superfamily while a putative sodium-dependent permease of the solute-sodium symporter family may mediate uptake of galactose and a facilitator protein of the major intrinsic protein family may internalize glycerol . Of the predicted gene clusters, reverse transcriptase PCRs showed active gene expression in 8 of 11 systems . Together with the previously surveyed permeases of the phosphotransferase system that accounts for the uptake of fructose and N-acetylglucosamine, the genome of S . coelicolor encodes at least 53 potential carbohydrate uptake systems.

Biochem J, 2004 May 15, 380(Pt 1), 193 - 202
Oxidation and reduction of pyridine nucleotides in alamethicin-permeabilized plant mitochondria; Johansson FI et al.; The inner mitochondrial membrane is selectively permeable, which limits the transport of solutes and metabolites across the membrane . This constitutes a problem when intramitochondrial enzymes are studied . The channel-forming antibiotic AlaM (alamethicin) was used as a potentially less invasive method to permeabilize mitochondria and study the highly branched electron-transport chain in potato tuber (Solanum tuberosum) and pea leaf (Pisum sativum) mitochondria . We show that AlaM permeabilized the inner membrane of plant mitochondria to NAD(P)H, allowing the quantification of internal NAD(P)H dehydrogenases as well as matrix enzymes in situ . AlaM was found to inhibit the electron-transport chain at the external Ca2+-dependent rotenone-insensitive NADH dehydrogenase and around complexes III and IV . Nevertheless, under optimal conditions, especially complex I-mediated NADH oxidation in AlaM-treated mitochondria was much higher than what has been previously measured by other techniques . Our results also show a difference in substrate specificities for complex I in mitochondria as compared with inside-out submitochondrial particles . AlaM facilitated the passage of cofactors to and from the mitochondrial matrix and allowed the determination of NAD+ requirements of malate oxidation in situ . In summary, we conclude that AlaM provides the best method for quantifying NADH dehydrogenase activities and that AlaM will prove to be an important method to study enzymes under conditions that resemble their native environment not only in plant mitochondria but also in other membrane-enclosed compartments, such as intact cells, chloroplasts and peroxisomes.

J Med Chem, 2004 Feb 26, 47(5), 1251 - 8
Design, synthesis, and evaluation of a liposaccharide drug delivery agent: application to the gastrointestinal absorption of gentamicin; Ross BP et al.; The design, synthesis, and evaluation of a liposaccharide (11) for use as an agent to enhance the gastrointestinal absorption of charged, hydrophilic drugs with poor membrane permeability is reported . 11 was designed to possess both surfactant and ion-pairing properties and was conveniently synthesized from d-glucuronic acid (2) and N-Boc-lipoamino acid (5) precursors in eight steps in good yield . Isothermal titration microcalorimetry was used to determine the critical micelle concentration of 11 (in PBS) to be 2.09 +/- 0.01 mM with an enthalpy of demicellization of 4.91 +/- 0.11 kJ/mol . The ability of 11 to enhance the gastrointestinal absorption of the aminoglycoside antibiotic gentamicin (1), a hydrophilic polycation with negligible oral bioavailability, was assessed in vivo using rats . Rats dosed orally with a mixture of 11 (100 mg/kg) and 1 (60 mg/kg) had a statistically significant (P < or = 0.034) increase in Cmax, AUC120, and percent absolute bioavailability (F) compared to control 1 (60 mg/kg) alone . The highest bioavailability (F = 9.1 +/- 2.0%) was achieved by dosing with the mixture 11 (100 mg/kg) and 1 (15 mg/kg) . This represents a 6-fold increase in bioavailability compared to the control (F = 1.4 +/- 0.3%) . These results suggest that the molar ratio of 1:11 may be critical in optimizing the delivery system, a finding ascribed in part to the ion-pairing properties of 11 . The effect of 11 on the gastrointestinal mucosa was assessed using light microscopy to examine tissue samples from rats used in the pharmacokinetic study . No morphological changes were found in either the esophagi or duodena of the rats examined . One rat dosed with 11 (100 mg/kg) and 1 (60 mg/kg) exhibited slight gastric erosion, which could be attributed to 11.

Respir Med, 2004 Feb, 98(2), 99 - 107
COPD exacerbations: the importance of a standard definition; Pauwels R et al.; Efforts to assess the efficacy of new therapies in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) have been hampered by the lack of a widely agreed and consistently used definition . A variety of definitions have been used in clinical studies, based on changes in patient symptoms or the requirement for antibiotic therapy, oral steroids or hospitalisation . To date, none of these definitions have been assessed in detail for their reliability, responsiveness and validity determined . Considerable heterogeneity in the aetiology and manifestation of COPD exacerbations makes identification and quantification of defining symptoms extremely difficult . New approaches are therefore being sought with a view to identifying a serum or tissue marker that can be used as a valuable diagnostic tool . Improvements in data recording will also contribute to the accuracy of data retrieval and assessment . If we are to progress to a level of sophistication seen in the diagnosis and management of other diseases, it is evident that considerable research efforts will be required to improve our understanding of COPD exacerbations and develop a standard definition for these events, thereby facilitating the assessment of therapeutic approaches.

Dig Liver Dis, 2004 Jan, 36(1), 7 - 12
Empirical Helicobacter pylori "rescue" therapy after failure of two eradication treatments; Gisbert JP et al.; AIM: Even with the current most effective Helicobacter pylori treatment regimens, approximately 20% of patients do not eradicate the infection . Several "rescue" therapies have been recommended, but they still fail to eradicate H . pylori in approximately 20-30% of the cases . Our aim was to evaluate the efficacy of different rescue therapies prescribed to patients in whom two consecutive H . pylori eradication regimens had failed . METHODS: Design . Prospective single-centre study . Patients . Consecutive patients in whom two eradication regimens had failed to eradicate H . pylori . Intervention . Third eradication regimens included: (1) omeprazole-amoxicillin-clarithromycin for 7 days; (2) quadruple therapy with omeprazole-bismuth-tetracycline-metronidazole for 7 days; (3) omeprazole-amoxicillin-clarithromycin-bismuth for 14 days; and (4) omeprazole-amoxicillin-rifabutin for 14 days . H . pylori antibiotic susceptibility was unknown and, therefore, rescue regimens were chosen empirically . In no case, was the same regimen repeated . Outcome . H . pylori eradication was defined as a negative in 13C-urea breath test 8 weeks after completing the therapy . RESULTS: Forty-eight patients were included (mean age 45 years, 44% males, 82% with peptic ulcer and 18% with functional dyspepsia) . No patient was lost from follow-up . Adverse effects were described in 21% of the patients . One patient receiving omeprazole, amoxicillin and rifabutin was removed from medication due to adverse effects (vomiting) . Overall, mean H . pylori eradication with third therapy after failure of two eradication treatments was 34/48 (71%; 95% confidence interval 57-82%) by intention-to-treat and 34/47 (72%; 95% confidence interval 58-83%) by per-protocol . CONCLUSION: It seems that performing culture even after a second eradication failure may not be necessary, as it is possible to construct an overall strategy to maximise H . pylori eradication, based on the different possibilities of empirical treatment.

J Environ Sci (China), 2004, 16(1), 49 - 52
Rapid degradation of bensulfuron-methyl upon repeated application in paddy soils; Xie XM et al.; Rapid degradation of bensulfuron-methyl upon repeated application in paddy soils was studied . The results showed that the DT50 of bensulfuron-methyl was reduced from 16 d to 9 d in soil with one-year bensulfuron-methyl application . Rapid bensulfuron-methyl degradation was happened to previously untreated soil by addition 5% rapid bensulfuron-methyl adapted soil and was inhibited following pre-treatment with broad-spectrum antibiotic chloramphenicol . In bensulfuron-methyl adapted soil mineralisation of 14C labeled bensulfuronmethyl to 14CO2 occurred at a faster rate than with previously untreated soil . It was concluded that rapid bensulfuron-methyl degradation upon repeated application is probably linked to the adaptation of soil bacteria which can utilize bensulfuron-methyl as a source of carbon and energy.

Ann Periodontol, 2003 Dec, 8(1), 115 - 81
Systemic anti-infective periodontal therapy . A systematic review; Haffajee AD et al.; BACKGROUND: Periodontal diseases are infections and thus systemically administered antibiotics are often employed as adjuncts for their control . There are conflicting reports as to whether these agents provide a therapeutic benefit . RATIONALE: The purpose of this systematic review is to determine whether systemically administered antibiotics improve a primary clinical outcome measure, periodontal attachment level change . FOCUSED QUESTION: In patients with periodontitis, what is the effect of systemically administered antibiotics as compared to controls on clinical measures of attachment level? SEARCH PROTOCOL: The Pub/Med database was searched from 1966 to May 2002 . Searches were limited to human studies published in English . Hand searches were performed on the Journal of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal Research . References in relevant papers and review articles were also examined . SELECTION CRITERIA: INCLUSION CRITERIA: Trials were selected if they met the following criteria: randomized controlled clinical trials, quasi-experimental studies, and cohort studies of > 1 month duration with a comparison group; subjects with aggressive, chronic, or recurrent periodontitis and periodontal abscess; use of a single or a combination of systemically administered antibiotics(s) versus non-antibiotic therapy; and a primary outcome of mean attachment level change (AL) . EXCLUSION CRITERIA: Studies involving the use of low-dose doxycycline, combinations of locally plus systemic antibiotics, or where the control group included a systemically administered antibiotic were excluded . DATA COLLECTION AND ANALYSIS: A mean difference in AL between groups was available for all papers used in the meta-analysis . A standard deviation (SD) for the difference was used if provided or calculated from the SD or standard error of the mean (SEM) when provided for single measurements . Data were subset by antibiotic employed, type of adjunctive therapy, and disease type . Results were assessed with both fixed-effects and random-effects models . MAIN RESULTS: 1 . Twenty-nine studies, 26 RCTs and 3 quasi-experimental (36 comparisons), met the entry criteria . Total study population, both control and test groups, was estimated at over 1,200 . 2 . Twenty-two studies (27 comparisons) were used in the meta-analysis, evaluating if the antibiotics provided a consistent benefit in mean AL change for different patient populations, for different therapies, and for different antibiotics . 3 . For the majority of the comparisons, systemically administered antibiotics exhibited a more positive attachment level change than the control group in the study . The combined results were statistically significant (P < 0.001) . 4 . The systemic antibiotics were uniformly beneficial in providing an improvement in AL when used as adjuncts to scaling and root planing (SRP) and were consistently beneficial, although of borderline significance, when used as adjuncts to SRP plus surgery or as a stand alone therapy . 5 . When examining the effects of individual or combinations of antibiotics, it was found that there were statistically significant improvements in AL for tetracycline, metronidazole, and an effect of borderline statistical significance for the combination of amoxicillin plus metronidazole . 6 . Improvements in mean AL were consistent for both chronic and aggressive periodontitis subjects, although the aggressive periodontitis patients benefited more from the antibiotics . REVIEWERS' CONCLUSIONS: 1 . The use of systemically administered adjunctive antibiotics with and without SRP and/or surgery appeared to provide a greater clinical improvement in AL than therapies not employing these agents . 2 . The data supported similar effect sizes for the majority of the antibiotics; therefore, the selection for an individual patient has to be made based on other factors . 3 . Due to a lack of sufficient sample size for many of the antibiotics tested, it is difficult to provide guidance as to the more effective ones.

J Cell Biol, 2004 Feb 16, 164(4), 547 - 56
Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C-related protein reveals a primordial role in subcellular sphingolipid distribution; Malathi K et al.; Lipid movement between organelles is a critical component of eukaryotic membrane homeostasis . Niemann Pick type C (NP-C) disease is a fatal neurodegenerative disorder typified by lysosomal accumulation of cholesterol and sphingolipids . Expression of yeast NP-C-related gene 1 (NCR1), the orthologue of the human NP-C gene 1 (NPC1) defective in the disease, in Chinese hamster ovary NPC1 mutant cells suppressed lipid accumulation . Deletion of NCR1, encoding a transmembrane glycoprotein predominantly residing in the vacuole of normal yeast, gave no phenotype . However, a dominant mutation in the putative sterol-sensing domain of Ncr1p conferred temperature and polyene antibiotic sensitivity without changes in sterol metabolism . Instead, the mutant cells were resistant to inhibitors of sphingolipid biosynthesis and super sensitive to sphingosine and C2-ceramide . Moreover, plasma membrane sphingolipids accumulated and redistributed to the vacuole and other subcellular membranes of the mutant cells . We propose that the primordial function of these proteins is to recycle sphingolipids and that defects in this process in higher eukaryotes secondarily result in cholesterol accumulation . Copyright The Rockefeller University Press

Am J Respir Cell Mol Biol, 2004 Mar, 30(3), 251 - 60
Molecular mechanisms of pulmonary peptidomimetic drug and peptide transport; Groneberg DA et al.; The aerosolic administration of peptidomimetic drugs could play a major role in the future treatment of various pulmonary and systemic diseases, because rational drug design offers the potential to specifically generate compounds that are transported efficiently into the epithelium by distinct carrier proteins such as the peptide transporters . From the two presently known peptide transporters, PEPT1 and PEPT2, which have been cloned from human tissues, the high-affinity transporter PEPT2 is expressed in the respiratory tract epithelium . The transporter is an integral membrane protein with 12 membrane-spanning domains and mediates electrogenic uphill peptide and peptidomimetic drug transport by coupling of substrate translocation to a transmembrane electrochemical proton gradient serving as driving force . In human airways, PEPT2 is localized to bronchial epithelium and alveolar type II pneumocytes, and transport studies revealed that both peptides and peptidomimetic drugs such as antibiotic, antiviral, and antineoplastic drugs are carried by the system . PEPT2 is also responsible for the transport of delta-aminolevulinic acid, which is used for photodynamic therapy and the diagnostics of pulmonary neoplasms . Based on the recent progress in understanding the structural requirements for substrate binding and transport, PEPT2 becomes a target for a rational drug design that may lead to a new generation of respiratory drugs and prodrugs that can be delivered to the airways via the peptide transporter.

J Theor Biol, 2004 Mar 7, 227(1), 1 - 11
Models of phage growth and their applicability to phage therapy; Weld RJ et al.; Phage therapy is complicated by the self-replicating nature of phage . It is difficult to extrapolate from in vitro phage growth data to in vivo expectations, difficult to interpret in vivo data and difficult to generalize from one in vivo situation to another . Various generic models of phage growth have been used as the theoretical basis for understanding the kinetics of phage therapy . Here, we have experimentally tested the efficacy of such simple models to predict, qualitatively and quantitatively, the growth of phage and the phage proliferation threshold in vitro . Naturally occurring, antibiotic-resistant bacteria were used to measure the growth of phage in vivo . In homogenous, in vitro environments, the models were predictive of T4 phage growth on Escherichia coli RR1 . However, the models were not able to predict growth of T4 phage or K1-5 phage in the more complex environment of the rat's digestive tract . To explore fully the kinetics of phage therapy, more complex models need to be devised . We suggest that it may be necessary to consider and model the interactions between phage growth parameters and bacterial growth parameters.

Arch Pharm Res, 2004 Jan, 27(1), 31 - 4
Electrochemical behavior and square wave voltammetric determination of doxorubicin hydrochloride; Hahn Y et al.; The electrochemical behavior of doxorubicin hydrochloride was investigated by cyclic voltammetry (CV) and square wave voltammetry (SWV) . From CV and SWV studies of doxorubicin hydrochloride in the acetate buffers of various pH values, it was found that protons were involved in the reduction of the antibiotic at the H+/e- ratio at one (deltaEp/pH = -53 approximately -61 mV at 23 degrees C), proposing the electrochemical reduction of the quinone moiety in its anthraquinone aglycone . Its electrochemical behavior was pseudo-reversible in the acetate buffer of pH 3.5 by exhibiting the well-defined single cathodic and anodic waves and the ratio of Ip(a)/Ip(c) at approximately one over the scan rates of 10 approximately 100 mV/s . Fast and sensitive SWV showing a single peak of doxorubicin has been applied for its quantitative analysis using an acetate buffer of pH 3.5 . A linearity was obtained when the peak currents (Ip) were plotted against concentrations of doxorubicin in the range of 5.0 x 10(-7) M approximately 1.0 x 10(-5) M with a detection limit of 1.0 x 10(-7) M.

Int J Gynaecol Obstet, 2004 Jan, 84(1), 95 - 8
Saline infusion sonohysterography; American College of Obstetrics and Gynecologist Tecnology Assessment; Saline infusion sonohysterography consists of ultrasonographic imaging of the uterus and uterocervical cavity, using real-time ultrasonography during injection of sterile saline into the uterus . When properly performed, saline infusion sonohysterography can provide information about the uterus and endometrium . The most common indication for sonohysterography is abnormal uterine bleeding . sonohysterography should not be performed in a woman who is pregnant or could be pregnant or in a woman with a pelvic infection or unexplained pelvic tenderness . Physicians who perform or supervise diagnostic saline infusion sonohysterograpy should have training, experience, and demonstrated competence in gynecologic ultrasonography and saline infusion sonohysterography . Portions of this document were developed jointly with the American College of Radiology and the American Institute of Ultrasound in Medicine.

Saudi Med J, 2004 Feb, 25(2), 182 - 5
Endocarditis prophylaxis in children with congenital heart disease . A parent's awareness; Al-Jarallah AS et al.; OBJECTIVE: The aim of this study is to determine the parental knowledge of bacterial endocarditis prophylaxis (BEP) . METHODS: Parents of 205 patients attending the Pediatric Cardiology Clinics at King Khalid University Hospital, Riyadh, King Fahad University Hospital, Al-Khobar and Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia from July 1999 to June 2000, were interviewed by a standard questionnaire pertaining to their knowledge of their child's cardiac disease, medications, and BEP . The patients' cardiac lesions and current medications were verified by a review of medical records . Each patient's need for BEP was determined according to American Heart Association recommendations . RESULTS: All parents answered the interview questions . The patients' mean age was 5 years and 8 months with a range of one month to 15 years . One hundred and two (50%) parents were high school graduates . Fifty-two (25%) parents correctly defined endocarditis . Two hundred and one (98%) parents knew the correct name of their child's cardiac condition, and 46/50 (92%) of those on medication knew the names of their child's current medications . Only 113/176 (64%) parents with at risk children were aware of measures to prevent endocarditis . CONCLUSION: While most parents know the name of their child's heart lesion and current medications, parental knowledge of endocarditis and BEP was limited . Intensified education and awareness programs are needed in order to prevent potential major morbidity and mortality for pediatric patients with congenital heart disease.

J Gynecol Obstet Biol Reprod (Paris), 2004 Feb, 33(1 Suppl), S12 - 4
{Sickle cell disease in the neonatal period}; de Montalembert M; The prognosis of pregnancy in women with major sickle cell syndromes has improved greatly in recent years . Correction of maternal anemia with programmed transfusion has been a major advance . Rates of preterm birth and intra-uterine growth retardation nevertheless remain high in this population . A newborn affected with sickle cell disease does not develop complications of the disease, because the predominant fetal hemoglobin cannot co-polymerize with sickle hemoglobin . The rate of complications increases as the infant's hemoglobin synthesis switches from fetal to sickle hemoglobin . Neonatal screening of sickle cell disease patients enables early implementation of a comprehensive prevention program (daily antibiotic prophylaxy, immunization, parental education.) . A neonatal screening program, targeted with regard to the parents' ethnic background, has been implemented throughout metropolitan France since 1999 . In 2002, this program enabled early diagnosis of sickle cell disease in 313 newborns.

J Cataract Refract Surg, 2004 Jan, 30(1), 268 - 72
Nattrassia mangiferae keratitis after laser in situ keratomileusis; Jabbarvand M et al.; A 32-year-old man had photophobia and blurred vision 2 weeks after uneventful laser in situ keratomileusis to correct myopia . He was treated with steroids for suspected diffuse lamellar keratitis, antiherpetics, and antibiotic eyedrops, but the condition worsened and the patient developed further blurred vision, an inflamed eye, and pain . When referred to us, the patient had an extensive corneal ulcer with hypopyon and mycelia were reported in scrapings of the ulcer bed . Nattrassia mangiferae (Hendersonula toruloidea) was cultured from the specimen . The patient was treated with antifungal agents and 2 penetrating keratoplasties . At the last examination, the uncorrected visual acuity was 20/200.

Hematology, 2004 Feb, 9(1), 65 - 9
Clinical and laboratory study of an episode of cefotetan-induced severe hemolytic anemia; Franchini M et al.; BACKGROUND: Cephalosporins are frequently associated with positive direct antiglobulin tests (DAT) and may rarely cause immune hemolytic anemia (IHA) . We describe a patient who developed hemolytic anemia while she was receiving intravenous cefotetan . STUDY DESIGN AND METHODS: Immunohematologic studies of drug-dependent antibodies were performed by using cefotetan-treated red blood cells (RBCs) and untreated RBCs in the presence of cefotetan . RESULTS: The patient's serum contained antibodies that reacted with both drug-coated RBCs (adsorption mechanism) and with uncoated RBCs when cefotetan was added to the serum (immune complex mechanism) . The prompt recognition of the problem and discontinuation of the drug prevented the onset of renal failure and rapidly resolved the hemolytic reaction . CONCLUSION: Our report underlines the importance of close laboratory and immunohematologic monitoring of patients treated with cephalosporins in order to recognize swiftly any hemolytic reaction due to these antibiotics thus reducing the chance of serious sequelae.

Protein Expr Purif, 2003 Dec, 32(2), 317 - 22
Expression of N-formylated proteins in Escherichia coli; Spector S et al.; In bacteria, protein expression initiates with a formyl-methionine group . Addition of the antibiotic actinonin, a known peptide deformylase inhibitor, at the time of induction of protein expression results in the retention of the formyl group by the overexpressed protein . In addition, because deformylation is a prerequisite for removal of the initiating methionine, this post-translational processing step is also prevented by actinonin, and the N-formyl methionine residue is retained by proteins from which it is normally removed . We have demonstrated the applicability of this system for obtaining N-modified forms of several different proteins and use one of these modified molecules to show that the N-terminal amino group is not required for ClpXP degradation of proteins bearing an N-terminal recognition signal.

Ned Tijdschr Geneeskd, 2004 Jan 17, 148(3), 120 - 5
{Diagnosis and treatment of bronchiectasis}; van Haren EH et al.; Patients with bronchiectasis usually have chronic pulmonary infection with secondary obstructive airway disease . This disease has to be distinguished from chronic obstructive pulmonary disease (COPD) . The diagnosis is established with the help of high resolution CT scan of the thorax . Further diagnostic evaluation is necessary to identify aetiologic factors . The treatment is complicated and involves many aspects: treatment of underlying conditions, recognition of exacerbations, boosting of tracheobronchial clearance, treatment of haemoptysis, surgical resection of affected lung segments and antibiotic therapy . Antibiotic therapy can focus on treatment of exacerbations but chronic suppressive antibiotic therapy is also used . Favourable results have been reported for maintenance treatment with macrolids as well as anti-inflammatory therapy.

J Virol, 2004 Mar, 78(5), 2553 - 61
Analysis of the 3' cis-acting elements of rubella virus by using replicons expressing a puromycin resistance gene; Chen MH et al.; A rubella virus (RUB) replicon, RUBrep/PAC, was constructed and used to map the 3' cis-acting elements (3' CSE) of the RUB genome required for RUB replication . The RUBrep/PAC replicon had the structural protein open reading frame partially replaced by a puromycin acetyltransferase (PAC) gene . Cells transfected with RUBrep/PAC transcripts expressed the PAC gene from the subgenomic RNA, were rendered resistant to puromycin, and thus survived selection with this drug . The relative survival following puromycin selection of cells transfected with transcripts from RUBrep/PAC constructs with mutations in the 3' CSE varied . The 3' region necessary for optimal relative survival consisted of the 3' 305 nucleotides (nt), a region conserved in RUB defective-interfering RNAs, and thus this region constitutes the 3' CSE . Within the 3' CSE, deletions in the approximately 245 nt that overlap the 3' end of the E1 gene resulted in reduced relative survivals, ranging from 20 to <1% of the parental replicon survival level while most mutations within the approximately 60-nt 3' untranslated region (UTR) were lethal . None of the 3' CSE mutations affected in vitro translation of the nonstructural protein open reading frame (which is 5' proximal in the genome and encodes the enzymes involved in virus RNA replication) . In cells transfected with replicons with 3' CSE mutations that survived antibiotic selection (i.e., those with mutations in the region of the 3' CSE that overlaps the E1 coding region), the amount of replicon-specific minus-strand RNA was uniform; however, the accumulation of both plus-strand RNA species, genomic and subgenomic, varied widely, indicating that this region of the RUB 3' CSE affects plus-strand RNA accumulation rather than minus-strand RNA synthesis.

J Antimicrob Chemother, 2004 Mar, 53(3), 533 - 5 Epub 2004 Feb 12.
Diffusion of levofloxacin into bone and synovial tissues; Rimmele T et al.; OBJECTIVES: The degree of penetration of an antibiotic into the infected site is an important determinant of therapeutic success . Levofloxacin is widely used in the treatment of serious infections . However, there are only few studies concerning its diffusion into bone tissue and none concerning its diffusion into synovial tissue . Our objective was to quantify levofloxacin bone and synovial tissue penetration and to compare our data with the breakpoint for susceptible organisms . PATIENTS AND METHODS: In an open-label study, 12 subjects who were undergoing elective total hip replacement received a single, parenteral, 500 mg dose of levofloxacin . Plasma, cortical and cancellous bone, and synovial tissue samples were collected a mean of 1.2 h later and analysed by a validated HPLC method . RESULTS: The mean +/- S.D . plasma concentration of levofloxacin at the time of bone removal was 7.5 +/- 1.3 mg/L . The levofloxacin concentrations were 7.4 +/- 2.2 mg/kg in cancellous bone tissue and 3.9 +/- 1.2 mg/kg in cortical bone tissue . The levofloxacin concentration was 8.9 +/- 2.1 mg/kg in synovial tissue . The mean +/- S.D . ratios of levofloxacin concentration in bone and plasma (bone/plasma) were 1.0 +/- 0.4 for cancellous bone tissue and 0.5 +/- 0.1 for cortical bone tissue . The ratio of levofloxacin concentration in synovial tissue and plasma (synovial tissue/plasma) was 1.2 +/- 0.4 . CONCLUSIONS: The concentrations of levofloxacin achieved in cancellous and cortical bone tissue and in synovial tissue are greater than the breakpoint for susceptible organisms, which is < or =2 mg/L.

J Biol Chem, 2004 Apr 23, 279(17), 17197 - 204 Epub 2004 Feb 11.
Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I; Batandier C et al.; We have investigated the consequences of permeability transition pore (PTP) opening on the rate of production of reactive oxygen species in isolated rat liver mitochondria . We found that PTP opening fully inhibited H(2)O(2) production when mitochondria were energized both with complex I or II substrates . Because PTP opening led to mitochondrial pyridine nucleotide depletion, H(2)O(2) production was measured again in the presence of various amounts of NADH . PTP opening-induced H(2)O(2) production began when NADH concentration was higher than 50 microm and reached a maximum at over 300 microm . At such concentrations of NADH, the maximal H(2)O(2) production was 4-fold higher than that observed when mitochondria were permeabilized with the channel-forming antibiotic alamethicin, indicating that the PTP opening-induced H(2)O(2) production was not due to antioxidant depletion . Moreover, PTP opening decreased rotenone-sensitive NADH ubiquinone reductase activity, whereas it did not affect the NADH FeCN reductase activity . We conclude that PTP opening induces a specific conformational change of complex I that (i) dramatically increases H(2)O(2) production so long as electrons are provided to complex I, and (ii) inhibits the physiological pathway of electrons inside complex I . These data allowed the identification of a novel consequence of permeability transition that may partly account for the mechanism by which PTP opening induces cell death.

J Am Geriatr Soc, 2004 Mar, 52(3), 381 - 7
A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease; Loeb MB et al.; OBJECTIVES: To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimer's disease (AD) . DESIGN: Randomized, triple-blind, controlled trial . SETTING: Three tertiary care and two community geriatric clinics in Canada . PARTICIPANTS: One hundred one patients with probable AD and mild to moderate dementia . INTERVENTION: Oral daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months . MEASUREMENTS: The primary outcome was a change in Standardized Alzheimer's Disease Assessment Scale cognitive subscale (SADAScog) at 6 months . Secondary outcomes were changes in the SADAScog at 12 months and tests of dysfunctional behavior, depression, and functional status . RESULTS: There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence interval (CI)=-5.28 to -0.22, P=.034) . At 12 months, the difference between groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079) . The antibiotic group showed significantly less dysfunctional behavior at 3 months . There was no significant difference in adverse events between groups (P=.34) . There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups . CONCLUSION: Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD . The mechanism is unlikely to be due to their effect on C . pneumoniae . More research is needed to investigate these agents.

J Long Term Eff Med Implants, 2004, 14(1), 1 - 11
Laparoscopic gastrostomy and jejunostomy; Nagle AP et al.; BACKGROUND: The percutaneous/endoscopic gastrostomy (PEG) has rapidly replaced the surgical gastrostomy as the preferred route for enteral access . In patients who are not candidates for a PEG, we prefer a laparoscopic gastrostomy to an open gastrostomy . Similarly, in patients who require a surgical jejunostomy, we prefer a laparoscopic approach . Minimally invasive techniques have several advantages over the standard open surgery . The purpose of this article is to review the indications, various techniques, and outcomes of laparoscopic gastrostomy and jejunostomy tubes . DATA SOURCES: Medline search from 1959-2002 . CONCLUSIONS: The PEG remains the procedure of choice for placement of a gastrostomy . Laparoscopic gastrostomy is an excellent choice for patients who are not candidates for a PEG . Similarly, laparoscopic jejunostomy is an excellent choice for patients who require enteral access, but have contraindications to a gastrostomy tube . Placement of laparoscopic gastrostomy andjejunostomy tubes can be safely performed, and the success and complication rates of these procedures compare favorably with those of the corresponding open surgical procedure . Laparotomy is rarely needed to place enteral feeding tubes . Cost analysis has shown that laparoscopic procedures are similar to open procedures.

Org Lett, 2004 Feb 19, 6(4), 537 - 40
Total synthesis of (+)-acanthodoral by the use of a Pd-catalyzed metal-ene reaction and a nonreductive 5-exo-acyl radical cyclization; Zhang L et al.; {reaction: see text} The first total synthesis of the antibiotic acanthodoral (1) has been achieved from 3-methyl-2-cyclohexen-1-one in 19 steps in 2.1% overall yield . The synthesis features the use of a Pd-ene reaction in the presence of CO to form the endocyclic alkene 8, a nonreductive acyl radical cyclization reaction, and a ring contraction reaction by the Wolff rearrangement . (+)-Acanthodoral has also been synthesized starting from (+)-S-2,2-dimethyl-6-methylenecyclohexanecarboxylic acid.

Mar Biotechnol (NY), 2002 Jan, 4(1), 63 - 73
Stable integration and functional expression of flounder growth hormone gene in transformed microalga, Chlorella ellipsoidea; Kim DH et al.; Chlorella is an attractive organism for complex recombinant protein production because of its eukaryotic characteristics and low cost for large-scale culture . Protoplasts of C . ellipsoidea were transformed with a vector containing the flounder growth hormone gene (fGH) under the control of the cauliflower mosaic virus 35S promoter, and the phleomycin resistance Sh ble gene under the control of the Chlamydomonas RBCS2 gene promoter . The presence of introduced DNA was first determined by PCR amplification of both the fGH and Sh ble genes from genomic DNA isolated from transformants and fGH protein expression was detected by immunoblot analysis . Over 400 microg of fGH protein expression per one liter culture containing 1 x 10(8) cells/ml was estimated by ELISA . Stable integration of introduced DNA was confirmed by Southern blot analysis of genomic DNA digested with restriction enzymes . The introduced DNA and fGH expression were detected after seven successive transfers in media devoid of phleomycin, but stably remained in the presence of the antibiotic . Flounder fry fed on the transformed Chlorella revealed a 25% growth increase after 30 days of feeding.

J Health Commun, 2004, 9 Suppl 1, 3 - 11
Forty years of diffusion of innovations: utility and value in public health; Haider M et al.; This special issue is created to mark the 40th anniversary of Everett Rogers' Diffusion of Innovations (DOI) model . Diffusion is the process through which an innovation, defined as an idea perceived as new, spreads via certain communication channels over time among the members of a particular social system . A great deal of research in a variety of academic disciplines (about 5000 published studies so far) has been conducted on the diffusion of innovations over the past six decades . The areas of application for these studies range from hybrid seed corn to modern math, to the snowmobile to antibiotic drugs, to HIV/AIDS prevention (Rogers, 1995) . These investigations have led to a general model of the diffusion of innovations, which can be applied to the recent spread of the Internet or to any other new idea . Everett Roger's ground-breaking model has contributed to a greater understanding of behavioral change, including the variation in rates of adoption of innovations, and it has held a broad scope of practical applications in the field of public health.

Cutis, 2004 Jan, 73(1 Suppl), 19 - 28
The role of topical metronidazole in the treatment of rosacea; Wolf JE Jr; Many topical and oral pharmacologic agents have shown well-tolerated efficacy for the treatment of rosacea . Metronidazole was the first topical therapy approved for rosacea and is still considered the foundation therapy by many researchers and dermatologists . The efficacy and tolerability of topical metronidazole in combination with an oral antibiotic or as monotherapy to maintain remissions have been shown in multiple well-controlled trials.

Epidemiol Infect, 2003 Dec, 131(3), 1091 - 6
Community-based estimates of incidence and risk factors for childhood pneumonia in Western Sydney; MacIntyre CR et al.; The aim was to estimate the community incidence and risk factors for all-cause pneumonia in children in Western Sydney, Australia . A cross-sectional randomized computer-assisted telephone interview was conducted in July 2000, in Western Sydney . Parents of 2020 children aged between 5 and 14 years were interviewed about their child's respiratory health since birth . No verification of reported diagnosis was available . Logistic regression analysis was used to determine risk factors for pneumonia . A lifetime diagnosis of pneumonia was reported in 137/2020 (68%) children, giving an estimated incidence in the study sample of 7.6/1000 person-years . Radiological confirmation was reported in 85% (117/137) . Hospitalization was reported in 41% (56/137) and antibiotic therapy in 93% (127/137) of cases . Using logistic regression modelling, statistically significant associations with pneumonia were a reported history of either asthma, bronchitis or other lung problems and health problems affecting other systems . In most cases, the diagnosis of asthma preceded the diagnosis of pneumonia . The community incidence of all causes of pneumonia is not well enumerated, either in adults or in children . This study provides community-based incidence data . The incidence of hospitalization for pneumonia in this study is comparable to estimates from studies in comparable populations, suggesting that retrospective parental report for memorable events is likely to be valid . We found a relationship between pneumonia and childhood respiratory diseases such as asthma, which has implications for targeted vaccination strategies.

Lancet Infect Dis, 2004 Feb, 4(2), 75 - 83
Are we ready for universal influenza vaccination in paediatrics?
Principi N, Esposito S.
Recent studies have suggested that paediatric influenza is a greater medical problem than usually thought because it can cause excess hospitalisations, medical visits, and antibiotic prescriptions even in healthy children, especially those under 2 years . Furthermore, influenza in otherwise healthy children may have substantial socioeconomic consequences for the children and their household contacts . These findings have led many experts to encourage the more widespread use of influenza vaccine in childhood . Although the immunogenicity of the available vaccines is good and they are safe, well-tolerated, and highly effective in preventing influenza and its complications, economic data support universal vaccination only when indirect effectiveness is considered . However, infants aged 6-23 months, children with recurrent acute otitis media or respiratory-tract infections, and healthy children attending day-care centres or elementary schools should be included among the paediatric groups requiring vaccination.

Plant Cell Rep, 2004 May, 22(10), 774 - 9 Epub 2004 Feb 10.
Kanamycin-resistant alfalfa has a point mutation in the 16S plastid rRNA; Rosellini D et al.; Genes conferring resistance to kanamycin are frequently used to obtain transgenic plants as spontaneous resistance to kanamycin is not known to exist in higher plants . Nevertheless, mutations conferring kanamycin resistance have been identified in Chlamydomonas reinhardtii, raising the question as to why kanamycin-resistant mutants have not been found in higher plants . While attempting plastid transformation of alfalfa, we obtained non-transgenic but kanamycin-resistant somatic embryos following 2 months of culture in the presence of 50 mg l(-1) kanamycin . Sequencing of the plastid DNA region corresponding to the decoding site of the 16S rRNA in ten independent resistant events revealed an A to C transversion at position 1357 of the 16S plastid rDNA, the same site at which an A to G conversion confers kanamycin resistance to C . reinhardtii by reducing the ability of the antibiotic to bind to its target site . All plants derived from the resistant embryos through additional cycles of somatic embryogenesis in the absence of kanamycin retained the mutant phenotype, suggesting that the mutation was homoplastomic . Resistant plants produced 85% less biomass than controls; their leaves were chlorotic during early development and over time slowly turned green . The absence of kanamycin- resistant mutants in higher plants might be explained by the requirement for a regeneration system capable of resulting in homoplastomic individuals, or it may be the result of the detrimental effect of the mutation on the phenotype .

BMJ . 2004 Feb 28;328(7438):487 . Epub 2004 Feb 09.
Adenoidectomy versus chemoprophylaxis and placebo for recurrent acute otitis media in children aged under 2 years: randomised controlled trial; Koivunen P et al.; OBJECTIVE: To evaluate the efficacy of adenoidectomy compared with long term chemoprophylaxis and placebo in the prevention of recurrent acute otitis media in children aged between 10 months and 2 years . DESIGN: Randomised, double blind, controlled trial . SETTING: Oulu University Hospital, a tertiary centre in Finland . PARTICIPANTS: 180 children aged 10 months to 2 years with recurrent acute otitis media . INTERVENTION: Adenoidectomy, sulfafurazole (sulphisoxazole) 50 mg/kg body weight, given once a day for six months or placebo . Follow up lasted for two years, during which time all symptoms and episodes of acute otitis media were recorded . MAIN OUTCOME MEASURES: Intervention failure (two episodes in two months or three in six months or persistent effusion) during follow up, number of episodes of acute otitis media, number of visits to a doctor because of any infection, and antibiotic prescriptions Number of prescriptions, and days with symptoms of respiratory infection . RESULTS: Compared with placebo, interventions failed during both the first six months and the rest of the follow up period of 24 months similarly in the adenoidectomy and chemoprophylaxis groups (at six months the differences in risk were 10% (95% confidence interval -9% to 29%) and 18% (-2% to 38%), respectively) . No significant differences were observed between the groups in the numbers of episodes of acute otitis media, visits to a doctor, antibiotic prescriptions, and days with symptoms of respiratory infection . CONCLUSIONS: Adenoidectomy, as the first surgical treatment of children aged 10 to 24 months with recurrent acute otitis media, is not effective in preventing further episodes . It cannot be recommended as the primary method of prophylaxis.

Joint Bone Spine, 2004 Jan, 71(1), 39 - 43
Good outcomes of Lyme arthritis in 24 patients in an endemic area of Switzerland; Renaud I et al.; OBJECTIVE: To describe outcomes of treated Lyme arthritis in an endemic area of western Switzerland, where some of the first cases of Lyme disease outside the United States were reported . PATIENTS AND METHODS: We retrospectively studied 24 patients (15 males and nine females, mean age 38.7 years) managed by rheumatologists between 1994 and 1999 for Borrelia burgdorferi arthritis manifesting as monoarthritis (n = 20), oligoarthritis (n = 3), or polyarthritis (n = 1) . The knee was affected in 20 (85%) patients . Nine patients reported a history of tick bite and four of erythema chronicum migrans . All the patients but one had a high titer of antibodies to B . burgdorferi by ELISA and all but two had a positive immunoblot test (22 positive for all three types of B . burgdorferi found in Switzerland and one positive only for B . burgdorferi sensu stricto) . Joint fluid PCR for B . burgdorferi was done in nine patients and was positive in six . RESULTS: All 24 patients received antibiotic therapy, orally (n = 10) or parenterally (n = 14) . A second course of antibiotic therapy was used in four patients with persistent arthritis . A rapid response was noted in 13 patients . Intraarticular glucocorticoid therapy or a synoviorthesis was required in nine patients . After a mean follow-up of 40 months (range, 6-84 months), none of the patients had chronic arthritis but two reported persistent muscle or joint pain . CONCLUSION: Recurrent or chronic arthritis, which has been reported in treated patients in the United States, did not occur in our series . This may be ascribable to differences in B . burgdorferi subtypes, as in the United States only B . burgdorferi sensu stricto is found.

J Biomol Struct Dyn, 2004 Apr, 21(5), 713 - 24
Daunomycin intercalation stabilizes distinct backbone conformations of DNA; Trieb M et al.; Daunomycin is a widely used antibiotic of the anthracycline family . In the present study we reveal the structural properties and important intercalator-DNA interactions by means of molecular dynamics . As most of the X-ray structures of DNA-daunomycin intercalated complexes are short hexamers or octamers of DNA with two drug molecules per doublehelix we calculated a self complementary 14-mer oligodeoxyribonucleotide duplex d(CGCGCGATCGCGCG)2 in the B-form with two putative intercalation sites at the 5'-CGA-3' step on both strands . Consequently we are able to look at the structure of a 1:1 complex and exclude crystal packing effects normally encountered in most of the X-ray crystallographic studies conducted so far . We performed different 10 to 20 ns long molecular dynamics simulations of the uncomplexed DNA structure, the DNA-daunomycin complex and a 1:2 complex of DNA-daunomycin where the two intercalator molecules are stacked into the two opposing 5'-CGA-3' steps . Thereby--in contrast to X-ray structures--a comparison of a complex of only one with a complex of two intercalators per doublehelix is possible . The chromophore of daunomycin is intercalated between the 5'-CG-3' bases while the daunosamine sugar moiety is placed in the minor groove . We observe a flexibility of the dihedral angle at the glycosidic bond, leading to three different positions of the ammonium group responsible for important contacts in the minor groove . Furthermore a distinct pattern of BI and BII around the intercalation site is induced and stabilized . This indicates a transfer of changes in the DNA geometry caused by intercalation to the DNA backbone.

J Neurosurg, 1971 Feb, 34(2 Pt 1), 142 - 4
Retained intracranial bone fragments: analysis of 42 patients; Hammon WM; Forty-two patients with retained intracranial bone fragments from Vietnam war wounds were evaluated and treated at the Walter Reed General Hospital . Forty required further debridement, 16 had positive wound cultures while they were on antibiotic therapy, 23 had gross evidence of infection, and the remainder also had debris and necrosis at the retained bone fragment sites . There were eight in-hospital deaths . All surviving patients available to follow-up have been free of infection . Retained intracranial fragments of bone should be removed as early as is possible.

Int J Oncol, 2004 Mar, 24(3), 591 - 608
Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: Role of exogenous dietary fatty acids, p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-kappaB; Menendez JA et al.; A biologically aggressive subset of human breast cancers has been demonstrated to overexpress fatty acid synthase (FAS), the key enzyme of endogenous FA biosynthesis . This breast cancer-specific activation of FAS-dependent lipogenesis, an anabolic-energy-storage pathway of minor importance in normal cells, would render breast cancer cells more vulnerable to anti-metabolite interventions with FAS as therapeutic target . Not surprisingly, pharmacological inhibitors of FAS have been reported to produce both cytostatic and cytotoxic effects in human breast cancer cells, as well as to suppress DNA replication . However, the signal transduction pathway(s) that link FAS hyperactivity and breast cancer cell growth has been unresolved . Here, we have attempted to provide a systematic approach to assess the role of FAS signaling on the survival and proliferation of human breast cancer cells . First, we assessed the level of FAS protein in a panel of human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-453, MDA-MB-435, ZR-75B, T47-D, BT-474, and SK-Br3) . FAS expression was graded from ++++ (overexpression) in SK-Br3 cells to + (very low expression) in MDA-MB-231 cells . No correlation was noted between FAS overexpression and estrogen receptor (ER) or progesterone receptor (PR) status, whereas a positive correlation was found between high levels of FAS expression and the amplification and/or overexpression of HER-2/neu oncogene . Because metabolic adaptation of breast cancer cells to the ambient fatty acid concentration may be relevant to the goal of utilizing FAS inhibition as a chemotherapeutic target, we evaluated the effect of exogenous dietary fatty acids on the cytotoxicity resulting from the inhibition of FAS activity . Pharmacological inhibition of FAS activity by the natural antibiotic cerulenin {(2S,3R)-2,3-epoxy-4-oxo-7E,10E-dodecadienamide} resulted in a dose-dependent cytotoxicity which positively paralleled the endogenous level of FAS . Supraphysiological levels of exogenous oleic acid (OA), a omega-9 monounsaturated fatty acid synthesized from a primary-end product of FAS palmitate, significantly diminished cell toxicity caused by cerulenin . Indeed, OA exposure significantly reduced FAS activity and expression by 55% in FAS-overexpressing SK-Br3 cells . omega-3 (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) and omega-6 (linoleic acid and arachidonic acid) polyunsaturated fatty acids (PUFAs), however, were unable to rescue breast cancer cells from cerulenin-induced cytotoxicity . Pharmacological blockade of FAS activity in FAS-overexpressing SK-Br3 cells resulted in apoptosis as determined by an enzyme-linked immunosorbent assay for histone-associated DNA fragments, and confirmed by TUNEL DNA-end labeling experiments . We further characterized signaling molecules that participate in the cellular events that follow inhibition of FAS activity and precede apoptosis in breast cancer cells . In SK-Br3 cells, cerulenin-induced inhibition of FAS activity resulted in down-regulation of p53, and up-regulation of cyclin-dependent kinase inhibitor (CDKi) p21WAF1/CIP1 . Treatment with cerulenin or a novel small-molecule inhibitor of FAS C75 resulted in a dramatic accumulation of CDKi p27KIP1, which was accompanied by a noteworthy translocation of p27KIP1 from cytosol to cell nuclei . Strikingly, FAS inhibition also caused a significant activation of the Raf-mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK1/2) cell survival pathway . Interestingly, we demonstrated that inhibition of FAS activity increased the nuclear-to-cytoplasmic ratio of BRCA1, a breast cancer tumor suppressor protein, as well as it induced a nuclear translocalization of the anti-apoptotic nuclear transcription factor-kappaB (NF-kappaB) . In conclusion, here we demonstrate that: a) breast cancer cells retain dependence on endogenous fatty acid synthesis and sensitivity to FAS inhibition in the presence of supraphysiological levels of dietary fatty acids, supporting the notion that FAS inhibition may be useful in treFAS inhibition may be useful in treating breast cancer in vivo; b) endogenous fatty acid synthesis is functional in breast cancer cells and is vital since its pharmacological inhibition is cytotoxic by promoting apoptosis, and c) specific blockade of FAS activity induces the accumulation, activation, and/or cellular relocalization of multiple and diverse pro- and anti-apoptotic signaling pathways, suggesting that p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-kappaB play a novel role in the breast cancer cell response to a metabolic stress after perturbation of FAS-dependent de novo fatty acid biosynthesis.

J Allergy Clin Immunol, 2004 Feb, 113(2), 291 - 6
The relationship between early fever and allergic sensitization at age 6 to 7 years; Williams LK et al.; BACKGROUND: The hygiene hypothesis suggests that early infections might protect against later allergic sensitization . OBJECTIVE: The purpose of this study was to determine whether fevers before age 1 year were associated with allergic sensitization at age 6 to 7 years . METHODS: Eight hundred thirty-five children from suburban Detroit, Michigan, were enrolled at birth . Clinic records from their first year were abstracted for episodes of fever, antibiotic use, and respiratory infections . Fever was defined as a rectal temperature of 38.3 degrees C (101 degrees F) or greater or its equivalent measured at another site . At age 6 to 7 years, 441 children underwent allergy testing . The primary outcome measures were atopy (>/=1 positive skin prick test result), seroatopy (>/=1 positive allergen-specific IgE level), and allergic sensitization (either seroatopy or atopy) . RESULTS: By age 1 year, 207 (46.9%) of the 441 participants had a documented fever . Among children with 0, 1, or 2 or more fevers in the first year, 33.3%, 31.3%, and 26.0% demonstrated atopy at age 6 to 7 years, respectively (P =.504); 43.4%, 39.7%, and 25.0% had seroatopy, respectively (P =.032); and 50.0%, 46.7%, and 31.3% had allergic sensitization, respectively (P =.028) . After adjusting for potential confounders, each febrile episode in the first year was associated with reduced odds for allergic sensitization (adjusted odds ratio, 0.69; 95% CI, 0.47-1.00) . Febrile upper respiratory tract infections, in particular, were associated with lower odds of allergic sensitization (adjusted odds ratio, 0.55; 95% CI, 0.31-0.97) per episode . CONCLUSION: This study provides direct support for the hygiene hypothesis because children with fevers before age 1 year were less likely to demonstrate allergic sensitivity at age 6 to 7 years.

Gynecol Oncol, 2004 Feb, 92(2), 592 - 5
Experience with the management of neutropenia in gynecologic cancer patients receiving carboplatin-based chemotherapy; Markman J et al.; Objective . There exists limited information in the medical literature regarding the incidence and severity of carboplatin-associated neutropenia, outside the setting of a clinical trial . We wished to examine this issue in a large single institution experience involving patients receiving both single agent and combination carboplatin-based chemotherapy for management of a female pelvic malignancy . Patients and methods . The medical records of women with gynecologic cancers treated with carboplatin-based chemotherapy at the Cleveland Clinic from January 1, 1998 through December 31, 2002 were retrospectively reviewed to determine the incidence and severity of neutropenia . Results . During the time period encompassed by this analysis, a total of 323 patients received 2145 cycles of carboplatin-based chemotherapy (total of 441 courses; median cycles/patient: 6 {range 1-27}) . The total number of each program utilized, and the incidence of grades 3 and 4 neutropenia observed (lowest nadir/regimen), were as follows: single agent carboplatin (178 courses; 5% grade 3, and <1% grade 4), carboplatin/paclitaxel (198; 23% and 6%), carboplatin/docetaxel (42; 17% and 73%) and carboplatin/paclitaxel/irinotecan (23; 39% and 61%) . Febrile neutropenia was uncommon, and there was only a single neutropenic-related death . Conclusion . Both single-agent carboplatin and carboplatin/paclitaxel result in a very low incidence of grade 4 neutropenia . While combining docetaxel with carboplatin or adding a "third drug" to carboplatin/paclitaxel substantially increases the incidence of severe neutropenia, neutropenic fever, and required hospitalizations for septic episodes are uncommon . The prophylactic oral administration of a broad-spectrum antibiotic (e.g., ciprofloxicin) in the presence of grade 4 neutropenia appears to be an effective strategy to minimize the risk of subsequent febrile events.

J Bone Joint Surg Br, 2004 Jan, 86(1), 65 - 9
The management of infection in arthroplasty of the shoulder; Coste JS et al.; The management and outcome of treatment in 42 patients (49 shoulders) with an infected shoulder prosthesis was reviewed in a retrospective multicentre study of 2343 prostheses . The factors which were analysed included the primary diagnosis, the delay between the diagnosis of infection and treatment and the type of treatment . Treatment was considered to be successful in 30 patients (71%) . Previous surgery and radiotherapy were identified as risk factors for the development of infection . All patients with an infected prosthesis had pain and limitation of movement and 88% showed radiological loosening . In 50% of the shoulders, the antibiotics chosen and the length of treatment were considered not to be optimal . The mean follow-up was 34 months . Antibiotics or debridement alone were ineffective . In acute infection, immediate revision with excision of all infected tissue and exchange of the prosthesis with appropriate antibiotic therapy gave the best results . Multidisciplinary collaboration is recommended.

Clin Infect Dis, 2004 Feb 15, 38(4), 542 - 6 Epub 2004 Jan 26.
Postoperative endophthalmitis; Hanscom TA; Postoperative endophthalmitis remains a serious clinical problem in ophthalmology, with an incidence of approximately 0.5% . Prognosis is largely determined by the virulence of the offending organism . The Endophthalmitis Vitrectomy Study (EVS) was a prospective, randomized trial comparing various diagnostic and treatment modalities in cases of endophthalmitis that followed cataract surgery . The EVS found that vitrectomy was only beneficial for patients presenting with very poor visual acuity and that intravenous antibiotic treatments had no additional benefit, compared with intravitreal antibiotic therapy alone . However, weaknesses of the EVS leave these conclusions open to modification in the future . Preoperative application of povidone-iodine preparation to the skin and conjunctiva is the only proven endophthalmitis prophylaxis . Endophthalmitis may be chronic and may follow glaucoma surgery and intravitreal injection of gas and drugs . The EVS did not study these issues, although they are associated with specific features that may require alterations in patient management.

Minerva Anestesiol, 2004 Jan-Feb, 70(1-2), 63 - 9
Candidemia in Intensive Care patients . Risk factors and mortality; Piazza O et al.; AIM: Aim of this study was to evaluate if the risk factors for candidemia could be used to identify patients who have a greater possibility of death after Candida spp blood infection . METHODS: A retrospective observational comparative study . SETTING: the Intensive Care Unit of an University Hospital . PATIENTS: 478 critical patients were included in this study . Neutropenic and immuno-suppressed patients were excluded . Interventions: routine care for acutely ill patients, with regard to their pathology . MEASUREMENTS: age, APACHE II at the admission, length of stay in the ICU before the diagnosis of candidemia and whole length of stay, outcome, risk factors for candidemia (Candida colonisation, previous antibiotic therapy, central vein, mechanical ventilation, abdominal surgery, hemodialysis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, diabetes, malignancy, splenectomy, immunosuppression, total parenteral nutrition, malnutrition) and clinical signs of multiorgan failure, systemic inflammatory response syndrome, sepsis or shock, concomitant presence of other infections . RESULTS: Twelve Candida spp blood infections were diagnosed . All the risk factors were homogenously distributed between patients who survived and those who died with the exception of the malnutrition state, associated with a higher mortality rate . CONCLUSION: If the candidemia is present, none of the risk factors for the onset of fungemia considered in this study, but the malnutrition state, are mortality predictors.

Medicina (Kaunas), 2004, 40(1), 84 - 91
{Intravenous catheters and nosocomial infection}; Reingardiene D; Peripheral, especially central venous catheters, are used with increasing frequency in the intensive care unit and in general medical wards to administer intravenous fluids and blood products, drugs, parenteral nutrition, and to monitor hemodynamic status . Catheter infection is associated with increased morbidity, mortality, and duration of hospital stay . Risk factors in the development of catheter colonization and bloodstream infections include patient factors (increased risk associated with malignancy, neutropenia, and shock) and treatment-related factors (increased risk associated with total parenteral nutrition, intensive care unit admission for any reason, and endotracheal intubation) . In this review article terms and definitions of catheter-related infections, pathophysiology and epidemiology of "catheter sepsis", factors determining risk of infection, catheter types and materials, insertion procedure, choice of insertion site, indwelling time, dressing and care of the insertion site, various preventive strategies and future developments, special situations and procedures, and treatment are discussed . Reducing catheter infections rates requires a multiple-strategy approach . Therefore, intensive care units and other locations where catheters are used should implement strict guidelines and protocols for catheter insertion, care, and maintenance.

Medicina (Kaunas), 2004, 40(1), 1 - 8
Nutrition of burned patients; Gudaviciene D et al.; Burns form 5-12% of all traumas . About 2,200 of patients are annually hospitalized in Lithuania . In most cases people of the employable age get burned . The treatment is often long-lasting, and afterwards recovered patients often have invalidity from burn sequels . The mortality of hospitalized burned patients is about 10% . The most common causes of death are pulmonary edema, pneumonia, sepsis and multiorgan failure . All these complications are related with insufficient nutrition . These complications are extremely frequent and dangerous for patients with more than 20% of body burned . The nutritional support of burned patient gives a possibility to increase the survival probability, to decrease complication rate and hospitalization time . Currently in Lithuania there are no standards for burned patient nutrition . More attention is given to strategy of surgical strategy and techniques, as well as antibiotic therapy . This article is the review of the different aspects of artificial nutrition of burned patient: indications, modes of nutrition, mixtures and terms of nutritional support.

Int Nurs Rev, 2004 Mar, 51(1), 56 - 64
Effects of acupuncture and care interventions on the outcome of inflammatory symptoms of the breast in lactating women; Kvist LJ et al.; OBJECTIVES: To compare modes of care and treatment for lactating women with inflammatory symptoms of the breast, with special focus on the use of acupuncture . METHOD: Eighty-eight mothers were randomized into three treatment groups . All three groups were given advice regarding emptying of the breasts and care in the form of comfort interventions . Acupuncture was included in the treatment regime for two of the groups . A severity index was created by adding together scores for signs and symptoms: breast tension, erythema and pain . FINDINGS: Mothers in all groups expressed relative satisfaction with the breastfeeding situation despite considerable discomfort . There was no significant difference between the groups for the number of mothers requiring more than three contact days for recovery nor for their severity index scores on day 3 . These findings must be interpreted with care but may suggest that care interventions play as great a part in the recovery of these women as acupuncture treatment or the use of oxytocin spray . Antibiotic therapy was used in 9% of the study population, which is in contrast to other studies . PROPOSED FUTURE ACTION: Based on these results, a new study has been designed to test the hypothesis that acupuncture hastens recovery from inflammatory processes in the lactating breast and approximately 200 mothers will be randomized in a new expanded study.

Allergy, 2004 Feb, 59(2), 148 - 50
Is the increase in allergic asthma associated with an inborn Th1 maturation or with an environmental Th1 trigger defect?
Wjst M.
The main reason for the asthma epidemic in industrialized countries is unknown . While childhood mortality from acute respiratory infection is still high in developing countries where asthma prevalence is low, there might be a suppressed natural selection in industrialized countries with a high asthma prevalence . Children with an inborn Th1 maturation defect might survive by better health care and antibiotic use at the cost of higher asthma and allergy rates . Another distinct group of children maybe represented by those having an environmental Th1 trigger deficit where the immune systems is not being sufficiently exposed in early life . Both, a Th1 maturation and a Th1 trigger defect may contribute to a dual Th1 allergy theory.

Acta Orthop Scand, 2003 Dec, 74(6), 670 - 6
The effect of mixing on gentamicin release from polymethylmethacrylate bone cements; Neut D et al.; We compared the release of gentamicin from 6 different commercially available, antibiotic-loaded PMMA bone cements used for vacuum- and hand-mixed cement using a Cemvac vacuum mixing system . We also measured the release of gentamicin after manual addition of the antibiotic to different commercial, unloaded bone cements after hand-mixing . The porosity of cements was reduced in all vacuum-mixed cements, as compared with hand-mixed cements, concurrent with a statistically significant reduction (3 of 6) or increase (1 of 6) in the total amounts of gentamicin released . The total gentamicin release was studied in 3 of the brands after manual addition and mixing of the antibiotics . We found that the release of antibiotics was lower than in samples made from industrial mixing . In conclusion, the manual addition and mixing of gentamicin in PMMA bone cements leads to a lower release of antibiotics than that in corresponding commercially available antibiotic-loaded cements, while vacuum-mixing only leads to a minor reduction in antibiotic release, as compared to hand-mixing.

J Antibiot (Tokyo), 2003 Nov, 56(11), 957 - 66
A relationship between the mevalonate pathway and isoprenoid production in actinomycetes; Kawasaki T et al.; Most Streptomyces strains are equipped with only the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the formation of isopentenyl diphosphate . In addition to this pathway, some Strepromyces strains have the mevalonate pathway to produce terpenoid antibiotics . We have previously shown that a gene cluster for biosynthesis of terpentecin, a diterpene antibiotic, was located in adjacent the mevalonate pathway gene cluster . In this study, a mevalonate pathway gene cluster was cloned from Actinoplanes sp . strain A40644, an isoprenoid antibiotic BE-40644 producer, to examine whether the mevalonate pathway genes and isoprenoid biosynthetic genes are clustered in genomic DNA . By sequencing flanking regions a probable BE-40644 biosynthetic gene cluster was found in the downstream region of the mevalonate pathway gene cluster . Heterologous expression of a 9-kb fragment confirmed that a set of the BE-40644 biosynthetic genes was involved in the fragment . This result suggested that the presence of the mevalonate pathway might be a good landmark to detect the production of isoprenoid compounds by actinomycetes.

Arch Esp Urol, 2003 Dec, 56(10), 1147 - 50
{A chicken bone as cause of Fournier gangrene}; Jalon Monzon A et al.; OBJECTIVES: Fournier's gangrene is a synergistic infective necrotizing fascitis, which involves perianal, perineal and genital regions, with rapid evolution and severe prognosis . We perform a literature review and report a recent case . METHODS: We report the case of a male patient who presented with scrotal pain and history of excretion of a chicken bone in a bowel movement . RESULTS: Despite aggressive surgery and wide spectrum antibiotic, the prognosis severe and the mortality is high . CONCLUSIONS: Rapid and accurate diagnosis remains the key to achieving a successful outcome . Early, wide and repeated debridement procedures reduce the mortality.

Med Trop (Mars), 2003, 63(4-5), 513 - 20
{Management of children with sickle cell disease in Africa: experience in a cohort of children at the Royal Albert Hospital in Dakar}; Diagne I et al.; Management of major sickle hemoglobinopathies in industrialized countries has improved significantly over the last few years thanks to strict application of the preventive and curative measures developed as a result of a better understanding of the underlying pathophysiological mechanisms . However patients in Africa have benefited little from progress in the field due to the lack of human and physical resources in sharp contrast with the high prevalence of the disease . The purpose of this study was to analyze problems involved in management of childhood sickle cell disease in Africa based on our experience in a cohort of 556 cases treated over a period of 12 years . The main problems were the same as those encountered in other black African nations, i.e., delayed diagnosis due to a lack of routine neonatal diagnostic screening, difficulty implementing anti-infectious prophylaxis due not only to the high cost of recommended vaccinations not covered by the Expanded Program on Immunization but also to poor compliance with antiobioprophylaxis, and insufficient transfusion facilities hindering application of long-term transfusion protocols when indicated . In addition the high prevalence of digestive-tract parasitosis and malaria raise the need to combine standard preventive measures with routine parasiticidal treatment and malarial prophylaxis adapted to each geographical area . The high frequency of associated iron deficiency requires systematic laboratory testing to identify and treat resulting manifestations during follow-up . An important prerequisite for widespread implementation of appropriate preventive and curative measures in Africa is recognition of sickle cell disease as a priority in public health care policy.

Allergy Asthma Proc, 2003 Nov-Dec, 24(6), 431 - 6
Specific inflammatory cell types and disease severity as predictors of postsurgical outcomes in patients with chronic sinusitis; Moran JV et al.; Chronic sinusitis is a common condition that is frequently refractory to medical and surgical intervention . It has not been well defined as to which patient subgroups benefit from surgical intervention and which do not . Our purpose is to determine whether the presence of certain inflammatory cell types is predictive of postoperative outcome in sinus surgery for chronic sinusitis . We performed a retrospective chart review of 75 patients who underwent endoscopic sinus surgery or polypectomy between 1994 and 1996 . Of these patients, 15 met inclusion criteria for chronic sinusitis, asthma requiring inhaled steroids, and 1 year preoperative and postoperative management by the allergist or otolaryngologist at Northwestern Medical Faculty Foundation . Ten of these 15 patients had a complete set of data allowing immunohistochemical analysis . Sections of sinus tissue obtained at surgery were hematoxylin and eosin stained and evaluated for the presence of lymphocytes, plasma cells, eosinophils, and macrophages . Immunostains for T lymphocytes, B lymphocytes, and macrophages were performed also . The total number of antibiotic courses patients received were enumerated into 6-month blocks for 1 year preoperatively and 1 year postoperatively as markers of disease activity . Postoperatively, four patients improved, three patients worsened, and three patients remained unchanged, as defined by the number of antibiotic courses required 1 year postoperatively compared with 1 year preoperatively . We found no difference in the magnitude or specific type of inflammatory cells present at the time of surgery between the groups . However, when the difference between the preoperative versus postoperative antibiotic courses was compared between patients who improved versus patients who did not improve, the improved group required markedly fewer courses relative to the nonimproved group (p < 0.009) . Neither total magnitude of inflammation nor specific inflammatory cell types correlated with surgical outcome in this group . The patients who did not improve postoperatively had a statistically significantly lower number of preoperative antibiotics than the patients who improved . These findings suggest that patients with less severe disease may be less likely to benefit from sinus surgery.

Allergy Asthma Proc, 2003 Nov-Dec, 24(6), 403 - 7
Therapy in the management of the rhinitis/asthma complex; Greenberger PA; Allergic rhinitis is a risk factor for the development of asthma, and, conversely, asthma often is present in patients with rhinitis (17-25% in children and 20-50% in adults) . Up to 80% of patients with asthma have allergic, nonallergic, or mixed rhinitis . Gastroesophageal reflux can be identified in 25-50% of patients with asthma and may be asymptomatic . Topical nasal corticosteroids typically reduce rhinitis symptoms more effectively than oral or topically administered histamine 1 antagonists but are similar in terms of ocular symptom reduction . The leukotriene D4 antagonist montelukast, as well as loratadine (29%), has been found to reduce nasal symptoms (27%) but the combination (33%) provided little additional benefit . Subcutaneous injections with a monoclonal anti-immunoglobulin E antibody for ragweed or birch allergic rhinitis have produced few anaphylactic reactions but when reactions occur, they appear 90-120 minutes after the injection . In the patients who received 300 mg of omalizumab every 3 or 4 weeks for ragweed allergic rhinitis, there were 23% fewer mean nasal symptoms than in placebo-treated subjects . In that study, antihistamines but not nasal corticosteroids were used during the study period . Overall, 70.7% of patients reported treatment as good or excellent compared with 40.8% in placebo-treated patients . The impact of omalizumab or other anti-immunoglobulin E therapies on rhinitis and asthma is being investigated . In patients experiencing acute, purulent, rhinosinusitis, treatment with a nasal corticosteroid helps relieve symptoms sooner than antibiotic and decongestant therapy alone . Treatment of rhinitis or rhinosinusitis and gastroesophageal reflux should be part of the management of patients with asthma.

Arerugi, 2004 Jan, 53(1), 34 - 7
{A case of latex allergy suspected drug allergy}; Yamaguchi Y et al.; A 30-year-old female with paroxysmal supraventricular tachycardia (PSVT) underwent catheter ablation . About 30 minutes later, urticaria and dyspnea occurred suddenly . Blood pressure decreased to 62/41 mmHg, and she fell into the state of anaphylactic shock . She recovered within one hour following treatment . We initially suspected the onset of anaphylaxis was caused by either the local anesthetic or the intravenous antibiotic administered . Following thorough investigation (skin tests and challenge tests), we concluded that the anaphylaxis was not drug induced . Subsequently, we suspected latex allergy . Skin prick test showed a positive reaction to rubber gloves . The specific test for IgE antibody against latex was positive at 10.8 UA/ml . From these results, anaphylactic shock caused by latex (probably medical gloves) was diagnosed . Doctors should take preventive measures against latex allergy not only in operating rooms but also during minor treatments . It is possible that latex allergy is responsible for some cases of anaphylaxis of unknown origin.

Fungal Genet Biol, 2004 Mar, 41(3), 336 - 48
Functional analysis of tvsp1, a serine protease-encoding gene in the biocontrol agent Trichoderma virens; Pozo MJ et al.; Serine proteases are highly conserved among fungi and considered to play a key role in different aspects of fungal biology . These proteases can be involved in development and have been related to pathogenesis or biocontrol processes . A gene (tvsp1) encoding an extracellular serine protease was cloned from Trichoderma virens, a biocontrol agent effective against soilborne fungal pathogens . The gene was expressed in Escherichia coli and a polyclonal antibody was raised against the recombinant protein . The expression pattern of tvsp1 was determined and its physiological role was addressed by mutational analysis . Strains of T . virens in which tvsp1 was deleted (PKO) or constitutively overexpressed (POE) were not affected in growth rate, conidiation, extracellular protein accumulation, antibiotic profiles nor in their ability to induce phytoalexins in cotton seedlings . Tvsp1 overexpression, however, significantly increased the ability of some strains to protect cotton seedlings against Rhizoctonia solani . Our data show that Tvsp1 is not necessary for the normal growth or development of T . virens, but plays a role in the biocontrol process.

Arch Pediatr, 2004 Feb, 11(2), 175 - 9
{Does selective digestive decontamination prevent nosocomial infections?}; Leclerc F et al.; Paediatric intensive care and haematological units are ideal sites for the development of nosocomial infections . These infections remain a significant source of mortality and morbidity and increase length of stay and costs . Selective digestive decontamination (SDD) includes topical antibiotics during the entire intensive care unit (ICU) stay, parenteral antibiotic administered for three to five days, hand hygiene and surveillance cultures of throat and rectum . Its use is based on the observation that resistant bacteria are often imported by the patients themselves, and the fact that transmission via the hands of carers could be responsible only for infections occurring after one week . In adult patients, seven meta-analyses have demonstrated that SDD reduces the odds ratio for lower airway infections, and sometimes mortality (particularly in surgical and trauma patients) . The main criticism against SDD is the possible emergence of antibiotic resistant bacteria, which is a growing problem in Europe and United States of America . Only four studies on SDD in children have been reported in the literature: due to methodological weaknesses and small size of samples, definitive conclusion cannot be drawn . However, one study in a 20 bed paediatric intensive care unit has demonstrated that SDD prevent both infections and the emergence of resistant bacteria . Furthermore, it has been demonstrated that more than 50% of children carrying resistant bacteria are detected within 24 hours of admission, suggesting that they import the resistant strains onto the intensive care unit . Factors that predict facility, administration of i.v . antibiotics within the past 12 months, previous intensive care unit admission and hospitalization of a household contact within the past 12 months . As suggested by several authors, the term selective should mean selection of appropriate patient groups (those at high risk of nosocomial infection, e.g . patients mechanically ventilated for at least 48 hours) and units (excluding those where multiresistance is endemic) . Obviously, surveillance of patient and unit bacterial ecology and improvement of antibiotic policy must be reinforced.

J Clin Periodontol, 2003 Nov, 30(11), 1011 - 5
Acellular dermal matrix allograft used to gain attached gingiva in a case of epidermolysis bullosa; Buduneli E et al.; BACKGROUND: Epidermolysis bullosa (EB) is an acquired disease or inherited as either autosomal dominant or recessive with an incidence of 1/50,000 . The prominent clinical characteristic of the disease is the development of bullae or vesicles in mucosa or skin in response to minor trauma . AIM: A female patient with a dystrophic type of EB had been put in a maintenance regimen after completion of the initial phase of periodontal therapy and followed for 7 years . The purpose of this report is to document acellular dermal matrix allograft application to increase the width of the attached gingiva in this patient experiencing difficulty in chewing and performing plaque control due to the dramatic loss of attached gingiva after 7 years of supportive periodontal therapy . METHODS: Under local anaesthesia and antibiotic coverage, the acellular dermal matrix allograft was applied in the anterior region of the upper jaw in order to increase the width of attached gingiva, thereby improving patient comfort . RESULTS: The healing was uneventful and a significant gain in attached gingiva dimensions was observed 9 months after the periodontal surgery . The procedure avoided a second surgical site, provided satisfactory results from an aesthetic point of view, and improved patient comfort . CONCLUSION: Acellular dermal matrix allograft may be regarded as an alternative in the treatment of EB cases to increase the width of attached gingiva and facilitate maintenance of the dentition.

Best Pract Res Clin Anaesthesiol, 2004 Mar, 18(1), 175 - 87
Influence of renal replacement therapy on pharmacokinetics in critically ill patients; Bugge JF; Critical illness has a great impact on many pharmacokinetic parameters . An increased volume of distribution often results in drug underdosing, whereas organ impairment may lead to drug accumulation and overdosing . Renal replacement therapy (RRT) in critically ill patients with renal failure may significantly increase drug clearance, requiring drug-dosing adjustments . Drugs significantly eliminated by the kidney are likely to experience substantial removal during RRT, and a supplemental dose--corresponding to the amount of drug removed by RRT--should be administered . Mechanisms of drug removal during RRT are reviewed together with methods for measuring or estimating RRT drug clearances . Approaches for drug-dosing adjustments are suggested and, at the end, the pharmacological principles for antibiotic prescription in the critically ill are discussed.

Pathology, 2004 Feb, 36(1), 77 - 81
The value of polymerase chain reaction detection of Mycobacterium tuberculosis in granulomas isolated by laser capture microdissection; Selva E et al.; AIMS: The aim of this study was to investigate the usefulness of polymerase chain reaction (PCR) detection of Mycobacterium tuberculosis in granulomas isolated by laser capture microdissection (LCM) . METHODS: The PCR DNA amplification method was used to detect M . tuberculosis in granulomas microdissected from one section stained by haematoxylin and eosin (H&E) from a formalin-fixed paraffin-embedded specimen . The results were compared to those obtained from PCR performed from 10 whole paraffin sections of 5 micro m each, and with the histology, culture and the patient's clinical findings . RESULTS: Forty-nine formalin-fixed and paraffin-embedded samples from 49 patients with a histological suspicion of a mycobacterial infection were investigated . Using culture as the reference method, the sensitivity for the detection of M . tuberculosis was 92% and the specificity was 100% using PCR from microdissected granulomas and were similar to those obtained by using PCR from 10 whole sections . CONCLUSIONS: The PCR method of examination of microdissected granulomas from deparaffinised sections is a sensitive, specific and rapid method for the detection of M . tuberculosis in formalin-fixed and paraffin-embedded samples . The method is as sensitive as that using PCR on 10 whole tissue sections, thus making it suitable for small biopsies . However, although these methods reduce the delay in diagnosis, culture remains the gold standard for identification of mycobacteria in tissue . Culture also allows for the testing of antibiotic sensitivity of any isolated species, in this way determining appropriate treatment.

Eur J Pharm Sci, 2004 Feb, 21(2-3), 217 - 23
Pharmacokinetic models for the saturable absorption of cefuroxime axetil and saturable elimination of cefuroxime; Ruiz-Carretero P et al.; Since oligopeptidic drugs such as beta-lactam antibiotics share the same carriers in humans and animals, the absorption and elimination kinetics of cefuroxime (C) were investigated in rats . Plasma C concentrations were measured by liquid chromatography . Pharmacokinetics and bioavailability of C in the rat were examined after intravenous (i.v.) administration at three doses (1.78, 8.9 and 17.8mg) of cefuroxime sodium and oral administration at two doses (2.02 and 8.9mg) of cefuroxime axetil (CA) . Preliminary fits using data from intravenous administration of C showed that the drug disposition kinetics were clearly nonlinear, with an increase in plasma clearance as the intravenous dose increased . After oral administration of CA, normalized C(max) was higher for smaller dose than for the largest dose . The population pharmacokinetic parameters were obtained by means of nonlinear mixed effect modelling approach according to a nonlinear elimination and nonlinear absorption two-compartment model . The nonlinear elimination could be attributed to a saturable renal tubular reabsorption of the antibiotic and nonlinear intestinal absorption of CA mediated by carrier system . The oral bioavailability of C, calculated by numeric integration of an amount of CA drug absorbed was 22 and 17% for 2.02 and 8.9mg of prodrug administered orally.

FEMS Microbiol Lett, 2004 Jan 30, 230(2), 185 - 90
Isolation and characterization of the tobramycin biosynthetic gene cluster from Streptomyces tenebrarius; Kharel MK et al.; The biosynthetic gene cluster for tobramycin, a 2-deoxystreptamine-containing aminoglycoside antibiotic, was isolated from Streptomyces tenebrarius ATCC 17920 . A genomic library of S . tenebrarius was constructed, and a cosmid, pST51, was isolated by the probes based on the core regions of 2-deoxy-scyllo-inosose (DOI) synthase, and L-glutamine:DOI aminotransferase and L-glutamine:scyllo-inosose aminotransferase . Sequencing of 33.9 kb revealed 24 open reading frames (ORFs) including putative tobramycin biosynthetic genes . We demonstrated that one of these ORFs, tbmA, encodes DOI synthase by in vitro enzyme assay of the purified protein . The catalytic residues of TbmA and dehydroquinate synthase were studied by homology modeling . The gene cluster found is likely to be involved in the biosynthesis of tobramycin.

An Pediatr (Barc), 2004 Feb, 60(2), 125 - 32
{Epidemiology and burden of acute otitis media in Valencia (Spain)}; Garces-Sanchez M et al.; OBJECTIVE: To assess the burden (incidence, treatment and complications) of acute otitis media (AOM) and otitis media with effusion (OME) in children younger than 5 years of age from Valencia, Spain . SUBJECT AND METHODS: We performed a retrospective cohort study of 1,399 children followed-up for the first 5 years of life . Seventeen pediatricians reviewed the medical records of their patients born in 1995 and 1996 and followed-up from birth until the age of 5 years . For each child, the number of otitis episodes, treatment, complications, and surgical interventions was obtained . RESULTS: There were 2,961 episodes of AOM in the first 5 years of life (2.23 cases/child) . Four hundred seventy-six cases (16.1 %) occurred before 1 year of age and 1,346 between the first and second year of life (45.5 %) . By the third year of life, 59.8 % had had at least one episode . In most children (80.9 %), diagnosis was made in primary care and required a median of 1.81 visits/episode for follow-up . A total of 94.5 % were treated with antibiotics (amoxicillin-clavulanate 38.8 %, cefuroxime 14.3 %, clarithromycin 8.2 % and amoxicillin 5.9 %) and 8.5 % required a change of antibiotic therapy . Two hundred seventeen children (15.2 %) had at least one episode of OME . Twenty-six patients (1.8 %, 95 % CI: 1.2-2.7 %) required insertion of ventilation tubes . Twenty-four patients (1.7 %) had secondary hypoacusis . There was one case of meningitis and two cases of chronic otorrhea . No cases of mastoiditis were recorded . CONCLUSIONS: The incidence of AOM in Valencia is 40,014 episodes/100,000 children younger than 5 years/year (95 % CI: 39,700-40,300) . It represents a significant burden due to the large number of visits, antibiotic use, associated surgical procedures and need for auditory rehabilitation.

Vasc Endovascular Surg, 2004 Jan-Feb, 38(1), 75 - 82
Management of infected aortic prosthetic grafts; Swain TW 3rd et al.; The management of infected prosthetic grafts is one of the most challenging problems facing vascular surgeons . High mortality and morbidity rates with traditional treatment have led many surgeons to consider different and novel strategies . Diagnosis is usually straightforward, but occasionally is unclear even after extensive clinical and radiologic investigations . Although routine total graft excision for all infected aortic grafts is still favored by some vascular surgeons, most favor only partial graft excision if only the distal limb of the graft is involved . Placement of in situ autologous vein or cryopreserved grafts have gained popularity, and investigations are continuing regarding the use of in situ antibiotic and silver-coated prosthetic grafts . In this article the authors review the incidence and etiology of aortic graft infections, methods to prevent these complications, the diagnosis of infected aortic grafts, and lastly the management of these complicated cases, including total graft excision and partial and complete graft preservation.

Phytochemistry, 2004 Feb, 65(4), 381 - 5
Four illudane sesquiterpenes from Coprinopsis episcopalis; Reina M et al.; Four new illudane derivatives with antibiotic and cytotoxic properties, illudins I (1), I(2) (2), J (3) and J(2) (4), have been isolated from the fungus Coprinopsis episcopalis (syn . Coprinus episcopalis) . These sesquiterpenes are stereoisomers, and their relative structures have been determined taking into consideration 2D NMR data.

Implant Dent, 2003, 12(4), 277 - 82
The use of implantoplasty and guided bone regeneration in the treatment of peri-implantitis: two case reports; Suh JJ et al.; A variety of treatment modalities have been proposed for the management of peri-implantitis . These are mostly based on empiric experience and use the systemic administration of an antibiotic in conjunction with surgical intervention . To ensure decontamination of the affected implant surface(s), chemical and/or mechanical debridement is used . For textured implant surfaces, detoxification using implantoplasty could also give favorable results when used as part of the procedure . Two cases are reported in which implants developed localized peri-implantitis lesions . Implantoplasty followed by topical tetracycline decontamination was used in conjunction with guided bone regeneration . In both cases, the procedures were effective in arresting disease and regenerating lost bone . These results suggest that the technique holds promise and should be investigated further.

Shock, 2004 Feb, 21(2), 99 - 102
Increased levels of serum sulfite in patients with acute pneumonia; Mitsuhashi H et al.; Sulfite, a common air pollutant, is toxic for humans, causing hypersensitivity or chronic airway diseases . We previously reported that sulfite is actively produced from neutrophils by stimulation with bacterial endotoxin, lipopolysaccharide (LPS) . We also found that the serum sulfite concentration is increased in a rat model of sepsis induced by systemic injection of LPS . However, information on sulfite metabolism in human inflammatory conditions is limited . In the current study, the serum concentration of sulfite was determined in 25 patients with acute pneumonia . Serum sulfite concentration in pneumonia patients was significantly higher than that in control subjects (3.75 +/- 0.88 vs . 1.23 +/- 0.48 microM, respectively, P < 0.05) . Among 20 patients, serum sulfite was serially determined before and after antibiotic therapy . The levels of serum sulfite were significantly reduced during the recovery phase compared with those during the acute phase (1.34 +/- 0.56 vs . 3.65 +/- 0.92 microM, respectively, P < 0.05) . Moreover, neutrophils obtained from three patients during the acute phase of pneumonia spontaneously produced higher amounts of sulfite in vitro than those obtained after recovery . There was a close positive correlation (r = 0.71, P < 0.05) between serum sulfite and C-reactive protein (CRP) in patients with pneumonia . Taken together, the current findings suggest that serum sulfite increases during systemic inflammation in humans . Activated neutrophils might be responsible, at least in part, for the up-regulation of sulfite . Given various biological effects reported previously, sulfite may act as a mediator in inflammation.

Science, 2004 Jan 30, 303(5658), 679 - 81
Lacticin 481: in vitro reconstitution of lantibiotic synthetase activity; Xie L et al.; The lantibiotic lacticin 481 is synthesized on ribosomes as a prepeptide (LctA) and posttranslationally modified to its mature form . These modifications include dehydration of serines and threonines, followed by intramolecular addition of cysteines to the unsaturated amino acids, which generates cyclic thioethers . This process breaks eight chemical bonds and forms six newbonds and is catalyzed by one enzyme, LctM . We have characterized the in vitro activity of LctM, which completely processed a series of LctA mutants, displaying a permissive substrate specificity that holds promise for antibiotic engineering.

Urology, 2004 Jan, 63(1), 176 - 7
Fournier's gangrene associated with sparganosis in the scrotum; Jeong HJ; Fournier's gangrene is a necrotizing fasciitis of the scrotum or perineum that may extend by way of the fascial planes to the penis and the anterior abdominal wall up to the clavicles, buttocks, or lower extremities . It is a life-threatening progressive disease that requires aggressive antibiotic therapy and early radical debridement . Sparganosis is a parasitic infection that occurs principally in cats and dogs, but human infestations have been reported, albeit rarely . Recently, we experienced a case of Fournier's gangrene associated with sparganosis in the scrotum, which was treated with antibiotics and extensive debridement including removal of a white, flat, shiny sparganum worm.

J Cardiol, 2004 Jan, 43(1), 31 - 6
{Acute myocardial infarction due to septic emboli in a patient with severe pneumonia: a case report}; Ogata C et al.; A 77-year-old man presented with acute anterior myocardial infarction and cardiogenic shock . We successfully performed coronary angioplasty and stenting with intra-aortic balloon pumping for a proximal lesion of the left anterior descending artery, which supplied the territory of the totally occluded right coronary artery . He also had pneumonia resistant to antibiotic therapy . On the 11th day after the onset of infarction, he suffered cardiogenic shock again and died . Postmortem histological examination demonstrated multiple septic emboli with neutrophil infiltration, resulting in myocardial infarctions . There was no occlusion at the stenting site . Severe pneumonia was found in both lungs, which may have been the embolic source in this case.

Gan To Kagaku Ryoho, 2004 Jan, 31(1), 61 - 5
{Clinical evaluation of cefozopran as treatment for febrile neutropenia}; Saito T et al.; Clinical effects and safety of cefozopran (CZOP) were evaluated by the Okayama Bone Marrow Transplantation Group . Twenty-five patients expected to experience febrile neutropenia during induction chemotherapy or consolidation chemotherapy of acute leukemia were enrolled between July 2000 and November 2002 . CZOP was administrated by drip infusion at 4g/day bid for a minimum of 3 days . The clinical effects and safety were evaluated in 20 patients with fever of 37.5 degrees C or more from a clinically suspected infection . The underlying disease was acute myeloid leukemia in 17 patients, acute lymphoid leukemia in 1 and acute promyelogeneous leukemia in 1 . The complicating infections were sepsis and suspected sepsis . Clinical efficacy was excellent in 11 patients, good in 1, fair in 2 and poor in 6, with an efficacy rate of 60.0% . The efficacy rate in patients whose albumin levels before therapy were less than 3.8 g/dl was 37.5%, whereas the rate in patients whose albumin levels before therapy were between 3.8 g/dl and 5.3 g/dl was 80.0% . The efficacy rate in patients whose neutrophil counts before therapy were less than 100/microliter was 50.0%, whereas the rate in patients whose neutrophil counts after therapy were less than 100/microliter was 53.8% . The efficacy rate in patients whose neutrophil counts both before and after therapy were less than 100/microliter was 37.5% . Side effect of exanthema was observed in 1 patient . These results indicate that CZOP is an effective and safe antibiotic for the treatment of febrile neutropenia in patients with hematological malignancies.

Zentralbl Chir, 2003 Dec, 128(12), 1038 - 46
Surgical wound infection surveillance; Lee JT; Measuring the frequency of a defined outcome flaw for a series of patients undergoing operative procedures generates information for performance evaluation . Such data influence decisions to improve care if used responsibly . Wound infection (WI), bacterial invasion of the incision, is the most common infectious complication of surgical care and WI prevention has value because the complication affects economic, patient satisfaction, and patient functional status outcomes . WI frequency, one kind of surgical outcome flaw rate, is traditionally used to judge one aspect of surgical care quality . At the author's institution, global WI surveillance was conducted without interruption for 20 years . Results for 85,260 consecutive inpatient operations performed during the period showed that secular changes in infection rates occurred but were not necessarily caused by surgical care quality decrements.

Hautarzt, 2004 Jan, 55(1), 74 - 6
{Folliculitis barbae in herpes simplex infection}; Lohrer R et al.; A 60-year-old male athlete developed a folliculitis in the beard region after several competitions . After identification of herpes simplex antigen within the lesions, systemic therapy with acyclovir led to rapid improvement . In folliculitis resistant to antibiotic and anti-inflammatory therapy, viral and mycotic infections as well as eosinophilic folliculitis should be considered as differential diagnostic possibilities.

J Trauma, 2004 Jan, 56(1), 123 - 7
Intravenous catheter complications in the hand and forearm; Kagel EM et al.; BACKGROUND: We studied the complications of peripheral intravenous (i.v.) catheters in the hand and forearm in a teaching hospital over a 3-year period . METHODS: The records of 67 patients who developed i.v . catheter-related complications were reviewed . RESULTS: The most common sites for developing complications in order of frequency were the forearm, hand, wrist, and antecubital fossa . There were 56 minor and 11 major complications . More than 50% of minor complications occurred in the hand and wrist, and more than 50% of major complications occurred in the hand . In 68% of minor complications, the patients were aged 50 years or older and 68% were women . Minor complications comprised 26 intravenous infiltrations, 23 cases of thrombophlebitis, and 7 cases of cellulitis . Ninety percent of major complication patients were aged 50 or older and 82% were women . Major complications included septic thrombophlebitis in three; hematomas resulting in skin necrosis in two; and infiltration related complications in six, resulting in skin necrosis in two, compressive nerve lesions in two, digital stiffness in one, and compartment syndrome in one . Ten patients with major complications were over the age of 50 years and nine were women . Two patients receiving anticoagulation developed large dorsal subcutaneous space hematomas . Chemotherapeutic agents contributed to two minor complications and one major complication . CONCLUSION: The hand is a common site for minor and major i.v . catheter complications . Women and older patients are more susceptible to these complications . Peripheral i.v . line complications are not uncommon and can result in morbidity and increased health care costs from prolonged hospitalization, extended use of i.v . antibiotic therapy, and surgical intervention.

J Trauma, 2004 Jan, 56(1), 111 - 7
Imipenem levels are not predictable in the critically ill patient; Belzberg H et al.; BACKGROUND: Critically ill patients often demonstrate extremely unusual volumes of distribution (Vd) and half-lives (t1/2) of drugs . Imipenem is a widely used antibiotic in critically ill patients . METHODS: We performed high-performance liquid chromatography analysis of imipenem in samples from 50 critically ill patients treated with either 500 or 1,000 mg . RESULTS: Peak imipenem levels varied from 1.56 microg/mL to 58.8 microg/mL . Trough levels varied between 0.0 microg/mL and 15.62 microg/mL . Only 54% of patients maintained a trough level greater than 4 microg/mL . Both the Vd and the t1/2 of imipenem were much greater than observed in other patient populations . CONCLUSION: The pharmacokinetic activity of imipenem in critically ill patients is different from that in other patient populations . There is a very weak correlation between dosage and serum concentrations . Therapeutic failures of imipenem may be because of unpredictable pharmacodynamics (Vd and t1/2) in critically ill surgical patients.

J Neurosurg Spine, 2004 Jan, 100(1), 52 - 5
Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats; Lee JY et al.; OBJECT: Extensive epidural fibrosis after lumbar surgery may be the underlying cause in most cases of failed-back surgery syndrome . Various materials have been used to prevent epidural fibrosis, but only moderate success has been shown . Mitomycin C, an alkylosing antibiotic substance isolated from Streptomyces caespitosus, potentially supresses fibroblast proliferation after surgery . In this study, the authors investigated the effect of mitomycin C by local application on spinal epidural fibrosis in a rat laminectomy model . METHODS: Five Wistar rats underwent laminectomy at cervical, thoracic, and lumbar levels . Based on data obtained from ophthalmological studies, mitomycin C was applied to the laminectomy sites in various concentrations (0.01, 0.05, and 0.1 mg/ml) . One laminectomy site in each rat was left untreated and thus served as a control . Evoked potentials were measured pre- and postoperatively, and all rats underwent clinical evaluation . Mobility status and evidence of neurological deficit were recorded . Twelve weeks later, the rats were killed, and the spinal column, including surrounding muscle tissue, was removed en bloc, decalcified, and fixed in formaldehyde . Epidural fibrosis was evaluated histologically . In all mitomycin C-treated laminectomy sites, epidural scarring was significantly reduced compared with control sites . Remarkably, dural adhesions were absent in laminectomy defects treated with mitomycin C concentrations of 0.05 and 0.1 mg/ml . Moderate to marked epidural fibrosis with adhesion to the dura mater was noted at sites receiving 0.01 mg/ml of mitomycin C . All control sites showed dense epidural fibrosis with marked dura adherence . CONCLUSIONS: In this experimental model, mitomycin C applied locally at a concentration of 0.1 mg/ml effectively reduced epidural fibrosis, completely avoided dural adherence, and induced no side effects.

Acta Orthop Belg, 2003 Dec, 69(6), 481 - 94
How to deal with bone exposure and osteomyelitis: an overview; Verhelle N et al.; The authors present an overview of the various techniques which can be used to achieve coverage of exposed bone, particularly in cases of bone exposure associated with an underlying fracture or osteomyelitis . Adequate debridement, possibly in several stages, is necessary in all cases to prepare the receptor site for the next step which is soft tissue coverage, achieved using various types of surgical procedures . Adequate reconstruction can be achieved with pedicled flaps in some cases but in cases with exposure of bone, free flaps usually represent a better option in cases where the condition of the patient is not a limiting factor . Thin fascio-cutaneous free flaps may be used in some cases with small and simple soft tissue loss, so as to minimise donor site mobidity . Free muscle flaps, such as from the latissimus dorsi, are preferable in cases with bone loss in order to fill any dead space; in cases with major bone loss, a free vascularised bone graft can be used, or composite grafts including bone, muscle and/or skin (fibula or crista iliaca flaps) . Some reconstructions require a functional approach, such as over an exposed joint, or for the weight-bearing area of the foot or the soft tissues over the Achilles tendon . Survival of a free flap requires perfect, permeable microsutures; thrombosis of the anastomosis is a major complication which jeopardizes flap survival; close surveillance of the flap is required during the first few days, with hourly Doppler monitoring of the pedicle on the first day . The success rate can be as high as 90 to 100% in simple cases; failures may be related to surgical technique, inadequate choice of the flap, or specific features of the patient . In cases with an underlying bone infection, recurrence of infection occurs in 5 to 20% of cases; this requires additional treatment, possibly with repeat debridement, prolonged antibiotic therapy and sometimes a second free flap.

J Virol, 2004 Feb, 78(4), 2137 - 41
Antiviral activity of distamycin A against vaccinia virus is the result of inhibition of postreplicative mRNA synthesis; Broyles SS et al.; Distamycin A has been described as an inhibitor of the cellular pathogenesis of vaccinia virus in culture . Distamycin is an antibiotic that specifically targets the minor groove of DNA . We show here that distamycin is a potent inhibitor of vaccinia virus replication . Pulse-labeling experiments showed that most major late proteins failed to accumulate in the presence of the antibiotic . We characterized the effect of distamycin on vaccinia virus nucleic acid biosynthesis with the goal of determining the inhibitor's target . Early gene transcription was unaffected . DNA synthesis proceeded at normal rates, but DNA accumulated in large masses in the cytoplasm with no evidence of virion assembly . Transcription from the intermediate class promoter for the I1L gene was partially reduced by distamycin; however, transcription from the intermediate promoters for the three late transcription factor genes was severely inhibited . The accumulation of the late transcripts for the viral F17R and A10L genes also was severely impaired and was shown to be a direct inhibition of late promoter activity . These results indicate that inhibition of postreplicative intermediate and late transcription is the basis for inhibition of vaccinia virus by distamycin and indicate that DNA minor-groove ligands hold promise for effective anti-poxvirus drugs.

Mol Biochem Parasitol, 2004 Mar, 134(1), 97 - 104
New selectable markers and single crossover integration for the highly versatile Plasmodium knowlesi transfection system; Wel A et al.; Plasmodium knowlesi provides a highly versatile transfection system for malaria, since it enables rapid genetic modification of the parasite both in vivo as well as in vitro . However, it is not possible to perform multiple genetic manipulations within one parasite line because of a lack of selectable markers . In an effort to develop additional selectable markers for this parasite, positive and negative selectable markers that have recently been successfully used in Plasmodium falciparum were tested . It was shown that the positive selectable markers human dihydrofolate reductase (hdhfr), blasticidin S deaminase (bsd) and neomycin phosphotransferase II (neo) all conferred drug resistance to P . knowlesi when introduced as episomes . The plasmid containing the hdhfr selectable marker was not only successfully introduced as circular form, but also as linear fragment, demonstrating for the first time single crossover integration in P . knowlesi . Thymidine kinase was tested for its potential as negative selectable marker and it was shown that recombinant P . knowlesi parasites expressing thymidine kinase from episomes were highly sensitive to ganciclovir compared to wild-type P . knowlesi . The availability of new positive selectable markers and a strong candidate for a negative selectable marker for P . knowlesi, in combination with the opportunity to perform targeted single crossover integration in P . knowlesi, significantly increases the flexibility of this transfection system, making it one of the most versatile systems available for Plasmodium.

Magn Reson Chem, 2004 Jan, 42(1), 49 - 54
Application of the TORO technique of 1H NMR to the structural analysis of cyclic peptide isomers having a slightly distorted symmetry from C2; Watanabe E et al.; The extended TORO technique was applied to the structural analysis of endo-D-Tyr-gramicidin S, cyclo(-Val-Orn-Leu-D-Phe-D-Tyr-Pro-Val-Orn-Leu-D-Phe-Pro-), which has a slightly distorted symmetry from C(2), by the insertion of D-Tyr and equivalent alpha-proton chemical shifts in the (1)H NMR spectrum . All NMR signals of the two dominant isomers of this antibiotic with trans-trans prolines were determined by using the extended TORO technique with TOCSY and ROESY spectra . This technique is generally applicable for distinguishing overlapped signals of alpha- and amide protons from the main chains of peptides .

J Clin Gastroenterol, 2004 Feb, 38(2), 110 - 4
High-dose versus low-dose clarithromycin in 1-week triple therapy, including rabeprazole and levofloxacin, for Helicobacter pylori eradication; Cammarota G et al.; GOALS: To compare high-dose versus low-dose clarithromycin in 1-week triple therapy including rabeprazole and levofloxacin . BACKGROUND: Regimens containing rabeprazole and levofloxacin have proved to be effective against H . pylori infection . STUDY: One-hundred H . pylori-positive patients were randomly assigned to one of the following 1-week regimens: rabeprazole 20 mg o.d . plus levofloxacin 500 mg o.d . and clarithromycin 250 mg b.d . (RLC-1 group); rabeprazole 20 mg o.d . plus levofloxacin 500 mg o.d . and clarithromycin 500 mg b.d . (RLC-2 group) . H . pylori status was assessed at entry and after the treatment . Patients who experienced treatment failure underwent antibiotic susceptibility testing . RESULTS: Forty-two patients in RLC-1 group (both PP and ITT analysis: 84%; 95%CI: 71-93%) and 47 in RLC2 group (both PP and ITT analysis: 94%; 95% CI: 83-98%) became H . pylori negative . Clarithromycin resistance was detected in all of 8 (100%) RLC-1 failures and in 1 out of 3 (33%) RLC-2 failures . Side effects occurred in 8% of patients in RLC-1 group and in 12% in RLC-2 . CONCLUSIONS: Regimens tested are competitive with other PPI-based treatments . One-week triple therapy containing rabeprazole plus, levofloxacin, and high-dose clarithromycin yielded a higher eradicating rate than the one containing low-dose clarithromycin and may be considered as a first-line therapy option.

J Control Release, 2004 Feb 10, 94(2-3), 365 - 79
Mechanism of bacitracin permeation enhancement through the skin and cellular membranes from an ethosomal carrier; Godin B et al.; The main objective of the present work was to investigate the dermal and intracellular delivery of bacitracin, a model polypeptide antibiotic, from ethosomes . Bacitracin and fluorescently labeled bacitracin (FITC-Bac) ethosomes were characterized for shape, lamellarity, fluidity, size distribution and entrapment capacity by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and ultracentrifugation, respectively . Confocal laser scanning microscopy (CLSM) experiments revealed that ethosomes facilitated the copenetration of antibiotic and phospholipid into cultured 3T3 Swiss albino mice fibroblasts . These results, confirmed by data obtained in fluorescent-activated cell sorting (FACS) experiments, suggest that ethosomes penetrate cellular membrane releasing the entrapped molecule within cells . Additional work was focused on skin permeation behavior of FITC-Bac from ethosomal systems in in vitro and in vivo experiments through human cadaver and rat skin, respectively . These studies demonstrated that the antibiotic peptide was delivered into deep skin layers through intercorneocyte lipid domain of stratum corneum (SC) . Occlusion had no effect on the permeation profile of the drug from ethosomes in in vitro experiments.Efficient delivery of antibiotics to deep skin strata from ethosomal applications could be highly beneficial, reducing possible side effects and other drawbacks associated with systemic treatment . Furthermore, ethosomal delivery systems could be considered for the treatment of a number of dermal infections, requiring intracellular delivery of antibiotics, whereby the drug must bypass two barriers: the SC and the cell membrane.

J Microbiol Methods, 2004 Feb, 56(2), 243 - 51
Characterization of the susceptibility of mycobacteria in BACTEC 12B media containing PANTA that had been supplemented with ceftazidime, and characterization of the individual components of PANTA in the presence of C18-carboxypropylbetaine; Thornton CG et al.; C(18)-carboxypropylbetaine (CB-18) specimen processing has enhanced the diagnosis of mycobacterioses by smear, culture, and nucleic acid amplification . However, toxic side effects of CB-18 in liquid culture, especially in the presence of antibiotics, have been reported . The interaction of CB-18 at 20-25 microg/ml with the individual components of the antibiotic supplement PANTA that had been fortified with ceftazidime (PANTA-caz) was characterized in BACTEC 12B cultures using four mycobacterial isolates . When the Mycobacterium tuberculosis isolate ATCC 27294 was examined CB-18 plus PANTA-caz did not significantly alter the time-to-positive (i.e., time to a growth index (GI) of 15 (GI(15))), but did significantly increase the time to a GI of 500 (GI(500)) by approximately 8.5 days . This result could be attributed primarily to nalidixic acid, but also to ceftazidime to a lesser degree . Statistically significant increases in GI(15) of 12.5 days and GI(500) of 16.5 days were observed in the presence of CB-18 plus PANTA-caz with the Mycobacterium avium isolate ATCC 25291 . These increases were due exclusively to trimethoprim . Statistically significant increases of approximately 2.5 and 9 days in GI(15) and GI(500), respectively, were observed with Mycobacterium kansasii ATCC 12478 in CB-18 plus PANTA-caz . The presence of nalidixic acid and ceftazidime were responsible for these alterations . When the behavior of the Mycobacterium fortuitum isolate ATCC 6841 was investigated in CB-18 plus PANTA-caz, significant increases in GI(15) of 8.5 days and GI(500) of 13 days were observed . The additive effects of nalidixic acid and azlocillin were responsible for these results . No single component of the PANTA-caz formulation was responsible for the interaction between CB-18 and PANTA-caz, although nalidixic acid contributed to these effects most often . These findings are consistent with the previous recommendation that CB-18 specimen processing follow a dilution-based format to ensure that the concentration of CB-18 carried-over into liquid media falls below 5-10 microg/ml.

Eur J Pediatr Surg, 2003 Dec, 13(6), 393 - 7
Treatment of post-appendectomy intra-abdominal deep abscesses; Dobremez E et al.; The treatment of acute appendicitis in children is sometimes followed by complications including intra-abdominal abscess, for which the traditional treatment is surgical drainage . We evaluated the efficacy of antibiotic management compared to classic surgical treatment . This retrospective study investigated 22 children from 5 to 13 years of age with one or many abscesses after appendectomy, treated between 1992 and 2002 . Eleven received surgery and the other 11 were treated with triple antibiotherapy . The two groups were comparable . Surgery was efficient in 36% of cases and complications occurred in 64% of cases (digestive fistula, intraperitoneal abscess, gaseous gangrene and septic shock) . Average hospital stay in this group was 16.7 days . In the other group, medication was efficient in 91% of cases; a recurrent abscess was operated and a residual stercolith, which was maintaining the infection, was removed . The average hospital stay in this group was 10.4 days . Medical treatment of intraperitoneal abscess seems to be effective . Hospitalisation is shorter with medical management and complications are rare . Therefore, medication may be proposed in most cases, except when there are residual foreign bodies or stercoliths . Poor patient status and septic shock are the two other contraindications, because antibiotherapy is not immediately efficient.

Drugs Today (Barc), 1998 Dec, 34(12), 1005 - 12
The chlamydial pneumonias; Cunha BA; Chlamydia psittaci and Chlamydia pneumoniae are important causes of community-acquired pneumonias . Less commonly, C . trachomatis may cause pneumonia in adult immunocompromised hosts but more commonly is responsible for pneumonia in neonates . C . psittaci is the cause of psittacosis and is the only chlamydial zoonotic atypical pneumonia . C . pneumoniae is being increasingly recognized as the cause of up to 10% of community-acquired pneumonias . C . pneumoniae pneumonia has a clinical presentation like Mycoplasma pneumoniae pneumonia . C . pneumoniae is also responsible for a variety of other respiratory tract infections, e.g., sinusitis, bronchitis, otitis, pharyngitis and laryngitis . C . pneumoniae, like M . pneumoniae, may result in permanent airway disease, e.g., asthma, following infection . All chlamydia are sensitive to doxycycline . Macrolides are highly active against C . trachomatis, and in spite of in vitro susceptibility, are relatively inactive in vivo against C . psittaci and C . pneumoniae . Fluoroquinolones are also active against chlamydia . Doxycycline remains the preferred antibiotic to treat all chlamydial infections in nonpregnant adults.

Rev Mal Respir, 2003 Dec, 20(6 Pt 1), 858 - 70
{Agreement between clinical practice guidelines for management of community-acquired pneumonia . A retrospective study of 101 hospitalized patients}; Labarere J et al.; INTRODUCTION: Management guidelines for acute community acquired pneumonia vary considerably . The objective is to estimate by a retrospective study the uniformity of the recommendations for the management of patients and the choice of initial empirical antibiotic therapy . METHODS: Eight English and French language guidelines published between 1998 and 2001 were identified by a search of the literature . They were applied retrospectively to a sample of 101 patients admitted to a university hospital in 2000 with a diagnosis of pneumonia . RESULTS: Hospital admission was advocated for between 61% and 95% and admission to intensive care for between 8% and 35% of the patients, depending on the guidelines under consideration . The actual management conformed to that advocated for between 34% and 94% of the patients (kappa=0.27 {0,19; 0,34}) . Compliance of the empirical antibiotic therapy (drug, dose, mode of administration) with the recommendations varied from 0% to 68% of the patients depending on the guidelines considered (kappa=0.01 {-0,10; 0,12}) . CONCLUSIONS: The heterogeneity of the guidelines is manifest by important variations in the recommendations for management and initial empirical therapy . These differences are due, in part, to a paucity of evidence based data upon which to base the guidelines . It would appear essential to harmonise the guidelines in a way that is appropriate for the country of their intended use.

Ann Pharmacother, 2004 Jan, 38(1), 15 - 9
High-dose versus standard-dose amoxicillin for acute otitis media; Garrison GD et al.; BACKGROUND: Emergence of drug-resistant bacteria has led to a recommendation to use high-dose (HD) amoxicillin (80-90 mg/kg/d) rather than standard-dose (SD) amoxicillin (40-45 mg/kg/d) to treat children with acute otitis media (AOM) . OBJECTIVE: To compare the efficacy and tolerability of HD versus SD amoxicillin among children with AOM who were considered at low risk for infection with antibiotic-resistant bacteria . METHODS: A double-blind, randomized, 3-year clinical trial was conducted using participants who met the following criteria: age >3 mo, weight </=18 kg, diagnosed with AOM, and candidates for treatment with amoxicillin . The primary endpoint was treatment success at a 3- to 4-day follow-up visit based on the clinical decision to continue the prescribed antibiotic therapy for AOM . Other endpoints included duration of illness, number of office visits and telephone calls related to illness, total number of subsequent AOM episodes, and number of adverse effects . RESULTS: The absolute difference in antibiotic failure rate with SD versus HD amoxicillin at the follow-up visit was nonsignificant (95% CI -1.5% to 3.4%; p = 0.78) . The mean duration of illness was similar for both doses of amoxicillin (3 +/- 2 d) . The number of office visits and telephone calls related to illness and the number of subsequent AOM episodes did not differ between the 2 treatment groups . HD amoxicillin did not result in a greater incidence of adverse effects than SD amoxicillin . CONCLUSIONS: HD amoxicillin had neither benefit nor detriment compared with SD for AOM in children at low risk for infection with antibiotic-resistant bacteria.

Int J Syst Evol Microbiol, 2004 Jan, 54(Pt 1), 235 - 9
Amycolatopsis decaplanina sp . nov., a novel member of the genus with unusual morphology; Wink J et al.; Strain DSM 44594T, which produces the glycopeptide antibiotic decaplanin, is a member of the genus Amycolatopsis based on 16S rRNA gene sequence analysis and chemotaxonomic properties . It is the first member of this genus that is reported to form pseudosporangia, which resemble those of members of the genus Kibdelosporangium . Phylogenetically, the novel taxon is related to Amycolatopsis orientalis, Amycolatopsis lurida, Amycolatopsis azurea, Amycolatopsis japonica and Amycolatopsis keratiniphila . Morphological, cultural and physiological properties, the production of a unique glycolipid and DNA-DNA similarity of <55% with phylogenetically related strains reveal that strain DSM 44594T represents a novel species of the genus, for which the name Amycolatopsis decaplanina sp . nov . (type strain, FH 1845T=DSM 44594T=NRRL B-24209T) is proposed.

Vet Microbiol, 2004 Feb 4, 98(2), 151 - 8
Immunosuppression in postweaning multisystemic wasting syndrome affected pigs; Segales J et al.; The present review concentrates on the clinical, pathological and immunological aspects of pigs suffering from PMWS which strongly suggest that PCV2 may be, in particular conditions, a cause of secondary immunodeficiency in pigs . From a clinical point of view, the lack of antibiotic therapy response against the disease, the existence of a litter effect and the concurrence of other disease syndromes and well-known secondary pathogens, such as Pneumocystis carinii, Chlamydia spp . and Aspergillus spp., may account as features of immunosuppression in PMWS . Furthermore, pathologic, immunohistologic and flow cytometric studies also suggest that pigs with PMWS may be immunosuppressed . Lymphocyte depletion of follicular and interfollicular areas together with macrophage infiltration of lymphoid tissues is a unique lesion, which is the basic feature of PMWS affected pigs . These findings are highly correlated with the decrease of circulating B- and T-cells and the diminution of these cell types in lymphoid organs, and with the increase of macrophage/monocytes lineage cells both in peripheral blood and lymphoid tissues in both naturally and experimentally PMWS affected pigs . The altered populations of cells participating in the immune system response both in blood and tissues suggests, at least in those severely PMWS affected pigs, a transient inability of diseased pigs to mount an effective immune response . From these points of view, strong suspicions on the immunosuppressive status of PMWS affected pigs do exist; however, future studies are needed to characterise the exact role of PCV2 on the immune system of pigs affected with PMWS.

Vet Clin North Am Equine Pract, 2003 Dec, 19(3), 765 - 78
Treatment of peritonitis; Davis JL; In summary, peritonitis in the horse is a potentially life-threatening disease that must be treated promptly and aggressively . Therapy should be aimed at reducing systemic shock and hypovolemia, correction of the primary cause, antibiotic and anti-inflammatory therapy, and abdominal drainage and lavage . The prognosis depends on the ability to diagnose and treat the underlying cause and prevent the development of complications . Mortality rates can be as high as 59.7%, with horses developing postoperative peritonitis having a 56% mortality rate . Long-term complications like adhesion formation or internal abscesses may further reduce the survival rate . The prognosis is best determined by an early and quick response to aggressive treatment.

Isr Med Assoc J, 2004 Jan, 6(1), 28 - 9
Therapeutic contact lens as the primary treatment for traumatic corneal erosions; Gilad E et al.; BACKGROUND: Corneal erosions, a common and very painful ailment, are traditionally treated with pressure patches and antibiotic ointment but the healing is slow . OBJECTIVES: To report our experience with the use of therapeutic contact lenses for the primary treatment of traumatic corneal erosions . METHODS: During the last 5 years in a single community clinic 65 consecutive patients with traumatic corneal erosions were treated with a corneal contact lens and antibiotic drops as a routine measure . The charts were reviewed for outcome, side effects and complications . RESULTS: Healing of the corneal erosions occurred within 1 to 3 days in all patients, with minimal or no pain . No corneal infection occurred . One patient had a recurrence that was successfully treated by lens placement . CONCLUSIONS: The therapeutic contact lens with antibiotic drops is a safe and effective method to treat traumatic corneal erosions, and patients can immediately resume their regular activities.

Laryngorhinootologie, 2004 Jan, 83(1), 40 - 50
{Dacryocystorhinostomy - state of the art, indications, results}; Keerl R et al.; BACKGROUND: In the ophthalmological literature external dacryocystorhinostomy (DCR) is considered the gold standard for the treatment of lacrimal duct stenoses . Rhinologists, on the other hand, favour the endonasal approach . MATERIALS AND METHODS: On the basis of an extensive review of the literature and our own longstanding experience we present an overview of the causes, the necessary diagnostic procedures and the surgical management of lacrimal duct stenosis . The outcomes of the two operative approaches are compared and special operative techniques and aids such as the use of laser, endoscopic dacryoplasty, silicone stenting, silicone cones with lacrimal duct stenting and the use of mitomycin C are discussed . RESULTS: The results published for endonasal DCR are slightly worse than those for the external operation . The success rates are around 90 % . Laser-assisted DCR and endoscopic dacryoplasty do not currently appear to yield better results than the conventional methods . Silicone stenting is not necessary in conventional endonasal DCR except in the case of presaccal stenosis . There are no established indications or treatment regimens for mitomycin C to date . Postoperative care after endonasal DCR should consist in the removal of fibrin, crusts and granulations and the administration of eye drops (antibiotic + cortisone) and nasal steroids . DISCUSSION: With appropriate operative technique and in experienced hands, the success rates of endonasal DCR are practically equal to those of the classical external approach . Major advantages of the endonasal approach are shorter operation times, lower complication rates and reduced patient morbidity . Neither silicone stenting nor the application of mitomycin C are routinely indicated . Laser-assisted techniques do not currently appear to improve results . Appropriate postoperative care is essential to prevent endonasal synechiae and subsequent recurrences.

Pediatr Transplant, 2003 Oct, 7(5), 376 - 80
Use of prophylactic lamivudine and mycophenolate mofetil in renal transplant recipients with chronic hepatitis B infection; Lau SC et al.; Chronic HBsAg carriers are known to have a higher risk of hepatitis-related mortality and morbidity when undergoing kidney transplantation . Immunosuppressants might flare up the infection that could be fulminating . Lamivudine and mycophenolate mofetil (MMF) have been shown to be effective in inhibiting replication of hepatitis B virus (HBV) . With these two drugs, hepatitis related adverse outcome might be preventable when these patients are being transplanted . Four Chinese adolescents with chronic HBV infection were transplanted in our Department from 1999 to 2001 . Immunosuppresants included prednisolone, cyclosporin A and MMF; azathioprine was not used for its potentially liver toxic effect . Prophylactic lamivudine 3 mg/kg and maximum 100 mg daily was given just before transplantation and was continued afterwards . HBV status and liver enzymes were monitored serially . Patients were followed up for 26.0 +/- 10.3 (11-34) months post-transplant and no mortality was reported . All grafts were functioning and no rejection was noted . MMF and lamivudine were well tolerated . Alanine transaminase was only transiently elevated in the first 2 months post-transplant in all patients and became normal afterwards . The patients were clinically well and liver function was normal at the last follow-up . However, HBV DNA became positive in three patients after the transplantation . YMDD mutant HBV was negative in one patient and undeterminable in the other three due to low virus load . In summary, with prophylactic lamivudine and MMF, short-term follow-up showed that renal transplant might be feasible and safe in chronic HBV carriers.

Clin Tech Small Anim Pract, 2003 Nov, 18(4), 211 - 7
Nutritional management of gastrointestinal disease; Zoran D; The gastrointestinal (GI) tract is primarily responsible for acquiring and digesting food, absorbing nutrients and water, and expelling wastes from the body as feces . A proper diet and normally functioning GI tract are integral for the delivery of nutrients, prevention of nutrient deficiencies and malnutrition, repair of damaged intestinal epithelium, restoration of normal luminal bacterial populations, promotion of normal GI motility, and maintenance of normal immune functions (eg, both tolerance and protection from pathogens) . The amount of food, its form, the frequency of feeding, and the composition of diet each have important effects on GI function and may be used to help ameliorate signs of GI disease . Although both nutrients and nonnutritional components of a diet are important to GI health, they also may cause or influence the development of GI pathology (eg, antibiotic responsive diarrhea, inflammatory bowel disease, dietary intolerance, or sensitivity and/or allergy) . The appropriate diet may have a profound effect on intestinal recovery and successful management of chronic or severe GI disease.

Med Sci Monit, 2004 Feb, 10(2), PI24 - 8
G-CSF in solid tumor chemotherapy: a tailored regimen reduces febrile neutropenia, treatment delays and direct costs; Tsavaris N et al.; BACKGROUND: Current guidelines do not recommend G-CSF for patients with risk factors for neutropenia . MATERIAL/METHODS: One-hundred patients undergoing chemotherapy were randomized to treatment with G-CSF at 5 Kg/kg for established febrile neutropenia (ANC <1000/microl) (Group A) or G-CSF at 263 Kg/day if ANC was 1500/microl or less on the day of the expected nadir, with the duration of treatment determined by the severity of neutropenia (Group B) . RESULTS: The number of doses of G-CSF was similar in the two groups . There were 34 cases of febrile neutropenia in Group A, but none in Group B (p=0.0001) . Hospital admission for febrile neutropenia, antibiotic use and delays in chemotherapy were all significantly more common in Group A . Total direct costs were estimated to be 66, 646 for Group A and 47, 119 for Group B . CONCLUSIONS: Tailoring treatment does not increase G-CSF use, but significantly reduces febrile neutropenia and treatment delays and lowers direct costs.

J Biol Chem, 2004 Apr 9, 279(15), 14752 - 62 Epub 2004 Jan 21.
TOR complex 1 includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in Saccharomyces cerevisiae; Reinke A et al.; The Tor1p and Tor2p kinases, targets of the therapeutically important antibiotic rapamycin, function as components of two distinct protein complexes in yeast, termed TOR complex 1 (TORC1) and TORC2 . TORC1 is responsible for a wide range of rapamycin-sensitive cellular activities and contains, in addition to Tor1p or Tor2p, two highly conserved proteins, Lst8p and Kog1p . By identifying proteins that co-purify with Tor1p, Tor2p, Lst8p, and Kog1p, we have characterized a comprehensive set of protein-protein interactions that define further the composition of TORC1 as well as TORC2 . In particular, we have identified Tco89p (YPL180w) and Bit61p (YJL058c) as novel components of TORC1 and TORC2, respectively . Deletion of TOR1 or TCO89 results in two specific and distinct phenotypes, (i) rapamycin-hypersensitivity and (ii) decreased cellular integrity, both of which correlate with the presence of SSD1-d, an allele of SSD1 previously associated with defects in cellular integrity . Furthermore, we link Ssd1p to Tap42p, a component of the TOR pathway that is believed to act uniquely downstream of TORC1 . Together, these results define a novel connection between TORC1 and Ssd1p-mediated maintenance of cellular integrity.

J Immunol Methods, 2004 Jan, 284(1-2), 187 - 94
AMEGA: antigen-mediated genetically modified cell amplification; Kawahara M et al.; Selection of genetically modified cells is a critical step to engineer the cells with desired properties . While antibiotic selection has been commonly used, administration of cytotoxic drugs often leads to deleterious effects not only to inert cells but also to transfected or transduced ones . To overcome this problem, a positive screening method for genetically modified cells is proposed using a pair of chimeric receptors that trigger a growth signal in response to a specific antigen . Either V(H) or V(L) region of anti-hen egg lysozyme (HEL) antibody HyHEL-10 was fused to extracellular D2 domain of erythropoietin receptor (EpoR) and transmembrane/cytoplasmic domains of either EpoR or gp130 . A model transgene, enhanced green fluorescent protein (EGFP) and the chimeric receptor genes that reconstituted functional Fv were retrovirally co-infected to interleukin (IL)-3-dependent Ba/F3 cells, followed by direct HEL selection in the absence of IL-3 . Consequently, a single round of selection led to a single population of EGFP-positive cells . The detailed protocol of the method termed antigen-mediated genetically modified cell amplification (AMEGA) is described.

Cardiovasc Intervent Radiol, 2004 May-Jun, 27(3), 204 - 7 Epub 2004 Jan 23.
Renal artery embolization: a first line treatment option for end-stage hydronephrosis; Mitra K et al.; Conventionally poorly functioning hydronephrotic kidneys have been removed if they are symptomatic . In our unit, patients are offered renal artery embolization as an alternative treatment option . PATIENTS AND METHODS: Fifteen patients (11 male, 4 female) with a mean age of 32.9 yr (20-51 yrs) have undergone renal artery embolization for symptomatic hydronephrosis with poor function . Mean follow-up was 64.13 weeks (range 14-200) . All patients had loin pain and hydronephrosis . Twelve patients had primary pelvi-ureteric junction obstruction (PUJO) . Two patients had poorly functioning hydronephrotic kidneys secondary to chronic calculous obstruction . One patient had chronic pain in an obstructed but reasonably functioning kidney following a previous pyeloplasty for PUJO which demanded intervention . Mean split function on renography was 11% (range 0-46%) . Selective renal artery embolization was carried out under antibiotic cover using a 7 Fr balloon occlusion catheter and absolute alcohol, steel coils, and polyvinyl alcohol particles . RESULTS: Nine patients developed post-embolization syndrome of self-limiting pain and pyrexia with no evidence of sepsis . One patient required readmission with this condition . One patient developed a hematoma at the puncture site . Mean hospital stay was 2.3 days . Fourteen patients are happy with the result and are completely pain free . One patient has minor discomfort but is delighted with the result . Nine patients have had follow-up ultrasound confirming resolution of the hydronephrosis . CONCLUSION: Renal artery embolization is an effective, safe, well-tolerated minimally invasive treatment option in end-stage hydronephrosis and we routinely offer it as an alternative to nephrectomy.

Clin Cancer Res, 2004 Jan 1, 10(1 Pt 1), 84 - 7
Camptothecin analogs (irinotecan or topotecan) plus high-dose cyclophosphamide as preparative regimens for antibody-based immunotherapy in resistant neuroblastoma; Kushner BH et al.; PURPOSE: We used high-dose cyclophosphamide plus topotecan/vincristine (CTV) or irinotecan (C/I) in patients with resistant neuroblastoma . The aim was to use a regimen with little risk to major organs to (a) achieve or consolidate remission in heavily treated patients and to (b) induce an immunological state conducive to passive immunotherapy with the murine 3F8 antibody . Experimental Design: CTV and C/I included cyclophosphamide 140 mg/kg ( approximately 4200 mg/m(2)) . With CTV, topotecan 2 mg/m(2) was infused i.v . (30 min) on days 1-4 (total, 8 mg/m(2)), and vincristine 0.067 mg/kg was injected on day 1 . With C/I, irinotecan, 50 mg/m(2) was infused i.v . (1 h) on days 1-5 (total, 250 mg/m(2)) . Mesna and granulocyte colony-stimulating factor were used . RESULTS: Twenty-nine patients received 38 courses of CTV, and 26 patients received 38 courses of C/I . All patients had previously received topotecan, a hemopoietic stem-cell transplant, and/or high-dose cyclophosphamide . CTV and C/I caused myelosuppression of comparably prolonged duration as follows: absolute neutrophil counts <500/ micro l lasted 5-12 days in patients who had not previously received transplant and 7-21 days in patients who were post-transplant . Other significant toxicities included typhlitis (two CTV-treated patients, one C/I-treated patient) and hemorrhagic cystitis (one C/I-treated patient) . Major responses were seen in 4 (15%) of 26 CTV and 4 (17%) of 24 C/I-treated patients with assessable disease . Bone marrow disease resolved in 5 (28%) of 18 CTV-treated patients and in 4 (27%) of 15 C/I-treated patients . 3F8 after CTV or C/I was not blocked by neutralizing antibodies, consistent with the desired immunosuppressive effect of high-dose cyclophosphamide . CONCLUSIONS: CTV and C/I require transfusional and antibiotic support but otherwise entail tolerable morbidity . They have modest antineuroblastoma activity in heavily treated patients and are good preparative regimens for passive immunotherapy with monoclonal antibodies.

J Ocul Pharmacol Ther, 2003 Dec, 19(6), 535 - 45
Effect of ofloxacin and netilmicin on human corneal and conjunctival cells in vitro; Papa V et al.; The purpose of this study was to compare the cytotoxic effects of the fluoroquinolone ofloxacin with that of the aminoglycoside netilmicin . Human corneal epithelial cells (HCE-T) and human conjunctival epithelial cells (Wong-Kilbourne derivative of Chang conjunctiva) were exposed to antibiotics (0.08-5.0 mg/mL) for 4 or 24 hours . Cell proliferation and viability were assessed with the MTT assay, neutral red uptake, and bromo deoxy uridine incorporation . In both cell lines, ofloxacin inhibited cell proliferation and viability . These effects were time and dose dependent . Concentrations of ofloxacin ranging from 0.4 to 2.4 mg/mL (0.04% to 0.24%) produced a 50% inhibition of proliferation and viability . In contrast, netilmicin induced no toxic effect . The differences between ofloxacin and netilmicin were highly statistically significant (p < 0.001) . This finding is particularly relevant in deciding the optimal antibiotic to be applied in clinical situations in which the epithelium is compromised.

Gastroenterol Clin Biol, 2003 Nov, 27(11), 1031 - 4
{Drainage-lavage and closure of a late esophageal perforation with esophagopleural fistula and encysted pleural effusion after endoscopic injection sclerotherapy for varices}; Mabrut JY et al.; We report a case of late perforation of the thoracic esophagus with an esophagopleural fistula after endoscopic sclerotherapy for esophageal varices in a Child-Pugh B9 cirrhotic patient . The existence of a thoracic empyema without diffuse mediastinitis allowed management of the fistula by percutaneous drainage-lavage and antibiotic therapy with subsequent closure of the esophageal wall defect and recovery from sepsis . This observation indicates that minimally invasive management of an esophageal perforation complicated by an esophago-pleural fistula is possible in highly selected patients.

Fungal Genet Biol, 2004 Feb, 41(2), 168 - 80
Genetic damage following introduction of DNA in Phycomyces; Obraztsova IN et al.; Introduction of plasmids in Phycomyces blakesleeanus caused extensive changes in the exogenous DNA and in the resident genome . Plasmids with a bacterial gene for geneticin resistance under a Phycomyces promoter were either injected into immature sporangia or incubated with spheroplasts . An improved method produced about one viable spheroplast per cell . Colonies resistant to geneticin were rare and only about 0.1% of their spores grew in the presence of geneticin . The transformation frequency was very low, < or =1 transformed colony per million spheroplasts or per microg DNA . Few nuclei in the transformants contained exogenous DNA, as shown by a selective procedure that sampled single nuclei from heterokaryons . The exogenous DNA was not integrated into the genome and no stable transformants were obtained . The plasmids were replicated in the recipient cells, but their DNA sequences were modified by deletions and rearrangements and the transformed phenotype was eventually lost . The spores developed in injected sporangia were often inviable; a genetic test showed that spore death was caused by impaired nuclear proliferation and induction of lethal mutations . About one-fourth of the viable spores from injected sporangia formed abnormal colonies with obvious changes in shape, texture, or color . The abnormalities that could be investigated were due to dominant mutations . The results indicate that incoming DNA is not only attacked, but signals a situation of stress that leads to increased mutation and nuclear and cellular death.

Mol Cell, 2004 Jan 16, 13(1), 113 - 24
Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin: the universally conserved residues G693 and C795 regulate P-site RNA binding; Dinos G et al.; The crystal structures of the universal translation-initiation inhibitors edeine and pactamycin bound to ribosomal 30S subunit have revealed that edeine induces base pairing of G693:C795, residues that constitute the pactamycin binding site . Here, we show that base pair formation by addition of edeine inhibits tRNA binding to the P site by preventing codon-anticodon interaction and that addition of pactamycin, which rebreaks the base pair, can relieve this inhibition . In addition, edeine induces translational misreading in the A site, at levels comparable to those induced by the classic misreading antibiotic streptomycin . Binding of pactamycin between residues G693 and C795 strongly inhibits translocation with a surprising tRNA specificity but has no effect on translation initiation, suggesting that reclassification of this antibiotic is necessary . Collectively, these results suggest that the universally conserved G693:C795 residues regulate tRNA binding at the P site of the ribosome and influence translocation efficiency.

Biochemistry, 2004 Jan 27, 43(3), 641 - 50
Stereochemical control of small molecule binding to bulged DNA: comparison of structures of spirocyclic enantiomer-bulged DNA complexes; Hwang GS et al.; The solution structure of the complex formed between an oligonucleotide containing a two-base bulge (5'-CACGCAGTTCGGAC.5'-GTCCGATGCGTG) and ent-DDI, a designed synthetic agent, has been elucidated using high-resolution NMR spectroscopy and restrained molecular dynamic simulation . Ent-DDI is a left-handed wedge-shaped spirocyclic molecule whose aglycone portion is an enantiomer of DDI, which mimics the spirocyclic geometry of the natural product, NCSi-gb, formed by base-catalyzed activation of the enediyne antibiotic neocarzinostatin . The benzindanone moiety of ent-DDI intercalates between the A6.T21 and the T9.A20 base pairs, overlapping with portions of the purine bases; the dihydronaphthalenone moiety is positioned in the minor groove along the G7-T8-T9 bulge sequence; and the aminoglycoside is in the middle of the minor groove, approaching A20 of the nonbulged strand . This alignment of ent-DDI along the DNA helical duplex is in the reverse direction to that of DDI . The aminoglycoside moiety of ent-DDI is positioned in the 3' direction from the bulge region, whereas that of the DDI is positioned in the 5' direction from the same site . This reverse binding orientation within the bulge site is the natural consequence of the opposite handedness imposed by the spirocyclic ring junction and permits the aromatic ring systems of the two spirocyclic enantiomers access to the bulge region . NMR and CD data indicate that the DNA in the DDI-bulged DNA complex undergoes a larger conformational change upon complex formation in comparison to the ent-DDI-bulged DNA, explaining the different binding affinities of the two drugs to the bulged DNA . In addition, there are different placements of the bulge bases in the helical duplex in the two complexes . One bulge base (G7) stacks inside the helix, and the other one (T8) is extrahelical in the DDI-bulged DNA complex, whereas both bulge bases in the ent-DDI-bulged DNA complex prefer extrahelical positions for drug binding . Elucidation of the detailed binding characteristics of the synthetic spirocyclic enantiomers provides a rational basis for the design of stereochemically controlled drugs for bulge binding sites.

Ann Otolaryngol Chir Cervicofac, 2003 Dec, 120(6), 359 - 62
{Myospherulosis of the maxillary sinus}; Godey B et al.; BACKGROUND: We present a case of a myospherulosis, describe the underlying cause and discuss ways of preventing its development . CASE REPORT: A 35-year-old man presented myospherulosis of the maxillary sinus caused by an antibiotic ointment placed in the sinus three years earlier during a Caldwell Luc procedure . The patient underwent a second Calwell Luc procedure . Outcome was uneventful and no recurrence was noted . DISCUSSION: Histological examination should be ordered at reoperation and petroleum-based ointments and packings should be avoided in sinus surgery.

ORL J Otorhinolaryngol Relat Spec, 2003 Sep-Oct, 65(5), 303 - 5
Refractory rhinosinusitis complicating immunosuppression: application of N-chlorotaurine, a novel endogenous antiseptic agent; Gstottner M et al.; Severe infections are a frequent complication in immunosuppression following transplantations . In the case reported here, a heart-transplanted patient was treated for refractory rhinosinusitis with a combination of sinus surgery and rinsing with N-chlorotaurine (NCT) . The daily rinse was well tolerated and effective . The combination of functional endonasal sinus surgery and topical treatment with NCT appeared effective and well tolerated in antibiotic-resistant sinusitis under immunosuppression .

J Mol Biol, 2004 Jan 30, 335(5), 1187 - 97
Structural and biochemical analysis of sliding clamp/ligand interactions suggest a competition between replicative and translesion DNA polymerases; Burnouf DY et al.; Most DNA polymerases interact with their cognate processive replication factor through a small peptide, this interaction being absolutely required for their function in vivo . We have solved the crystal structure of a complex between the beta sliding clamp of Escherichia coli and the 16 residue C-terminal peptide of Pol IV (P16) . The seven C-terminal residues bind to a pocket located at the surface of one beta monomer . This region was previously identified as the binding site of another beta clamp binding protein, the delta subunit of the gamma complex . We show that peptide P16 competitively prevents beta-clamp-mediated stimulation of both Pol IV and alpha subunit DNA polymerase activities, suggesting that the site of interaction of the alpha subunit with beta is identical with, or overlaps that of Pol IV . This common binding site for delta, Pol IV and alpha subunit is shown to be formed by residues that are highly conserved among many bacterial beta homologs, thus defining an evolutionarily conserved hydrophobic crevice for sliding clamp ligands and a new target for antibiotic drug design.

Am J Cardiovasc Drugs, 2002, 2(3), 163 - 72
Perspectives of drug-eluting stents: the next revolution; Moses JW et al.; Coronary stent implantation has become a well established therapy in the management of coronary artery disease (CAD) . Although the Stent Restenosis Study (STRESS) and Belgium-Netherlands Stent (BENESTENT) trials demonstrated convincingly that stenting is superior to percutaneous transluminal coronary angioplasty with respect to restenosis in de novo lesions, there is, however, still a high incidence (10 to 50%) of restenosis following stent implantation . Improvements in stent design and implantation techniques resulted in an increase in the use of coronary stents and today, in most centers in the US and Europe, stenting has become the predominant form of nonsurgical revascularization accounting for about 80% of all percutaneous coronary intervention procedures . Coronary stents provide luminal scaffolding that virtually eliminates elastic recoil and remodelling . Stents, however, do not decrease neointimal hyperplasia and in fact lead to an increase in the proliferative comportment of restenosis . Agents that inhibit cell-cycle progression indirectly have also been tested as inhibitors of vascular proliferation . When coated onto stents, sirolimus, a macrolide antibiotic with immunosuppressive properties, and paclitaxel and dactinomycin, both chemotherapeutic agents, induced cell-cycle arrest in smooth muscle cells (SMC) and inhibited neointimal formation in animal models . Preliminary clinical studies with drug-eluting stents produced dramatic results eliminating restenosis in large and mid-size arteries . Quantitative coronary angiography and intravascular ultrasound demonstrated virtually complete inhibition of tissue growth at 6 and 12 months after sirolimus-eluting stent implantation . Results are also very encouraging with paclitaxel-coated stents . However, it needs to be proven that current drug-eluting stents will produce similar results in 'real life' interventional practice (long lesions, lesions in small vessels, in vein grafts, chronic total occlusions, and bifurcated and ostial lesions) . The ongoing randomized, double-blind sirolimus-coated Bx Velocity trade mark balloon expandable stent in the treatment of patients with de novo coronary artery lesions (SIRIUS) trial may answer some of these concerns . With further improvements, including the expansion of drug-loading capacity, double coatings and coatings with programmable pharmacokinetic capacity using advances in nanotechnology (which may allow for more precise and controlled release of less toxic and improved molecules), we think that in the next few years the practice of interventional cardiology may undergo major changes . A new era of dramatic improvements in the treatment of CAD may have dawned . The prospect of approval of this technology should herald a host of clinical trials to revisit basic assumptions about the place of coronary stenting in the contemporary care of obstructive (and nonobstructive) CAD.

Eur J Clin Microbiol Infect Dis, 2004 Feb, 23(2), 82 - 8 Epub 2004 Jan 15.
Full-course oral levofloxacin for treatment of hospitalized patients with community-acquired pneumonia; Erard V et al.; Most guidelines for the management of hospitalized patients with community-acquired pneumonia (CAP) recommend commencing therapy with intravenous antibiotics, primarily because of concern about absorption of oral antibiotics in acutely ill patients . However, patients who respond are rapidly switched to oral therapy, which has been shown to reduce costs and to shorten the length of stay . The aim of the present study was to determine whether a full course of oral antibiotics is as efficacious and as safe as intravenous-to-oral sequential antibiotic therapy for the treatment of hospitalized, non-ICU patients with CAP . In an open-labelled, controlled study, 129 hospitalized patients with CAP were randomly assigned in a 2:1 ratio to receive either a full course of oral levofloxacin (500 mg q12 h) or an intravenous-to-oral sequential therapy consisting of intravenous ceftriaxone (2 g q24 h) with or without clarithromycin (500 mg q12 h) followed by an oral antibiotic (a beta-lactam agent in the majority of patients) . The primary study endpoint was the resolution of CAP; secondary endpoints included length of stay and overall mortality . CAP resolved in 72 of 79 (91.1%) patients in the levofloxacin group and in 34 of 37 (91.9%) patients in the intravenous-to-oral sequential therapy group (difference, -0.8%, 95%CI, -11.6-10.0) . Median length of stay was 8 days (range, 2-74 days) in the levofloxacin group and 10 days (range, 3-29 days) in the intravenous-to-oral sequential therapy group ( P=0.28) . Day 30 mortality rates were 1.3% (1 of 79) and 8.1% (3 of 37), respectively (difference, -6.8%, 95%CI, -16.0-2.3) . Full-course oral levofloxacin is as efficacious and as safe as standard intravenous-to-oral sequential antibiotic therapy for the treatment of hospitalized patients with CAP.

Plant Cell Rep, 2004 Apr, 22(9), 684 - 90 Epub 2004 Jan 15.
Pearl millet transformation system using the positive selectable marker gene phosphomannose isomerase; O'Kennedy MM et al.; Fertile transgenic pearl millet plants expressing a phosphomannose isomerase (PMI) transgene under control of the maize ubiquitin constitutive promoter were obtained using the transformation system described here . Proliferating immature zygotic embryos were used as target tissue for bombardment using a particle inflow gun . Different culture and selection strategies were assessed in order to obtain an optimised mannose selection protocol . Stable integration of the manA gene into the genome of pearl millet was confirmed by PCR and Southern blot analysis . Stable integration of the manA transgene into the genome of pearl millet was demonstrated in T1 and T2 progeny of two independent transformation events with no more than four to ten copies of the transgene . Similar to results obtained from previous studies with maize and wheat, the manA gene was shown to be a superior selectable marker gene for improving transformation efficiencies when compared to antibiotic or herbicide selectable marker genes.

Rev Chir Orthop Reparatrice Appar Mot, 2003 Dec, 89(8), 730 - 2
{Rare cause of acute carpal tunnel syndrome: acute metacarpal osteomyelitis}; Zitoun Y et al.; Acute carpal tunnel syndrome resulting from acute metacarpal osteomyelitis is an exceptional etiopathogenic entity . A 6-year-old boy developed an acute carpal tunnel syndrome on the left four days after trauma . The carpal tunnel was opened in an emergency setting and exploration revealed a pale median nerve with infiltration of neighboring tissue . After release, pus issued from the depth of the tunnel . A posterior approach disclosed the collection and a total loss of the 4th metacarpal periosteum, leading to the diagnosis of acute osteomyelitis . Edema and pain regressed rapidly with antibiotic therapy . A pathologic fracture of the 4th metacarpal discovered three months later was treated conservatively . At 10 months, the child has a very good functional result despite persistence of a short 4th metacarpal after healing . There was no motor or sensitive neurological deficit and thumb opposition was complete . We have been unable to find any other report of acute metacarpal osteomyelitis leading to acute carpal tunnel syndrome . Emergency treatment is crucial . Opening the annular ligament is the only way to achieve complete nerve recovery.

Ann Thorac Surg, 2004 Jan, 77(1), 186 - 90
Viability and histologic structure of porcine valves after cryopreservation; Rendal Vazquez ME et al.; BACKGROUND: Increased awareness of the limitations of current cardiac valve substitutes has generated a renewed interest in the use of allograft valves . The effects of currently used preservation techniques on the viability of the valve leaflets and the longevity of the implantation however remain controversial . The objective of this study is to analyze the influence of ischemic time, sterilization methods with or without fungicides, and storage procedures on the viability of the valve leaflets and on the histologic structure of the arterial wall, valve leaflet, and myocardium . METHODS: The tissue sources were hearts from 40 pigs with 1 hour of warm ischemic time . The aortic and pulmonary valves were dissected after 2 or 24 hours of cold ischemic time . They were stored in antibiotic solution for 20 hours at 4 degrees C with or without an antifungal agent . The samples were cryopreserved using a programmed temperature decrease method . After 1 week of storage in a liquid nitrogen tank, either in a gas or a liquid phase, the cardiac valves were slowly thawed and examined . RESULTS: Pulmonary valves showed greater viability than aortic valves . Decreased cellular viability was observed independent of cold ischemic time, treatment with amphotericin B, or the storage method used . Treatment with or without amphotericin B had no influence on cellular viability . Conversely it was observed that there was greater cellular viability among those valves stored in a liquid phase . As far as the histologic structure of the valve is concerned we did not observe any influence either in the treatment with amphotericin B or the storage method used although it was observed that reduction of the cold ischemic time minimized histologic injury . CONCLUSIONS: Optimization of preservation methods may decrease the negative effects of cryopreservation on cell viability and histologic structure of the valve.

Curr Treat Options Gastroenterol, 2004 Feb, 7(1), 19 - 28
Small Bowel Bacterial Overgrowth: Presentation, Diagnosis, and Treatment; Singh VV et al.; Small bowel bacterial overgrowth (SBBO) syndrome is associated with excessive numbers of bacteria in the proximal small intestine . The pathology of this condition involves competition between the bacteria and the human host for ingested nutrients . This competition leads to intraluminal bacterial catabolism of nutrients, often with production of toxic metabolites and injury to the enterocyte . A complex array of clinical symptoms ensues, resulting in chronic diarrhea, steatorrhea, macrocytic anemia, weight loss, and less commonly, protein-losing enteropathy . Therapy is targeted at correction of underlying small bowel abnormalities that predispose to SBBO and appropriate antibiotic therapy . The symptoms and signs of SBBO can be reversed with this approach.

Clin Exp Dermatol, 2004 Jan, 29(1), 8 - 14
A new type of minocycline-induced cutaneous hyperpigmentation; Mouton RW et al.; Pigmentary disorders are recognized adverse effects of the semi-synthetic tetracycline derivative antibiotic, minocycline . Three distinct types of minocycline-induced cutaneous pigmentation have been described . Type I, blue-black pigmentation confined to sites of scarring or inflammation on the face; Type II, blue-grey circumscribed pigmentation of normal skin of the lower legs and forearms; and Type III, diffuse muddy brown pigmentation of normal skin accentuated in sun-exposed areas . We report two patients with acne vulgaris with a fourth type of minocycline-induced cutaneous pigmentation . They presented with circumscribed blue-grey pigmentation within acne scars confined to the back . Histology showed pigment within dendritic cells, and extracellularly throughout the dermis . Histochemistry identified a calcium containing melanin-like substance . Iron was absent . Immunohistochemistry confirmed some pigment-containing cells to be macrophages . Electron microscopy demonstrated electron-dense granules, free and membrane-bound, within macrophages and fibroblast-like cells . Energy-dispersive X-ray analysis confirmed the presence of calcium . Iron was absent . This fourth type of cutaneous minocycline hyperpigmentation may be a variant of Type I, but based on clinical, pathological and microanalytical differences, appears to be a new entity . The pigment may be a drug metabolite-protein complex chelated with calcium, or an insoluble minocycline-melanin complex . We propose a classification of cutaneous minocycline pigmentation based on clinico-pathological criteria.

Mikrobiol Z, 2003 Sep-Oct, 65(5), 36 - 40
{Chemotherapy of experimental rickettsial infection under the influence of small doses of radiation}; Basarab NI; Radiation is of particular importance among a lot of environment factors dangerous for human health, including the effect of small dozes of radiation . State of rickettsial infection under the influence of small dozes of radiation and under administration of immunostimulator Imunal and antibiotic doxycyclin has been studied . Researches were conducted on guinea pigs, using the experimental rickettsial infection . Researches have shown that the use of immunostimulator Imunal and antibiotic doxycyclin had positive effect on the immunity indices of the experimental rickettsial infection in animals in the conditions of influence of small dozes of radiation.

Pediatr Nephrol, 2004 Feb, 19(2), 125 - 7 Epub 2003 Dec 10.
New insights on preventing and managing peritonitis; Piraino B; Methods to prevent peritonitis are an essential component of any successful peritoneal dialysis (PD) program . Careful attention to training of the parents and child on the proper technique of PD and avoidance of manual spiking by using an assist device for the cycler, or use of the double-bag system for continuous ambulatory PD, should decrease risk of peritonitis from touch contamination . Secondly, reduction of peritonitis can be achieved through reduction of exit site infections by use of mupirocin antibiotic cream at the exit site of the PD catheter as part of routine care . If an exit site infection develops and is refractory to therapy, then the PD catheter can be successfully replaced as a single procedure, to reduce the risk of peritonitis . The third step in reducing the risk of peritonitis is to avoid repetitive episodes with the same organism . This may again involve replacing the catheter; as long as the effluent can be cleared, this again can be performed as a single procedure, thus allowing the child to avoid the trauma of hemodialysis . The focus in pediatric PD programs must always be on preserving the peritoneal membrane, and not on preservation of the catheter . With careful attention, peritonitis can become an uncommon event.

Eur J Dermatol, 2003 Nov-Dec, 13(6), 590 - 2
Topical tacrolimus in the treatment of localized scleroderma; Mancuso G et al.; Although the cause of localized scleroderma is unknown, an autoimmune mechanism is suspected . We describe two patients with localized scleroderma treated with topical tacrolimus, an immunosuppressive macrolide antibiotic . Topical tacrolimus 0.1% ointment applied twice daily under occlusion led to a significant clinical improvement of late sclerotic lesions and complete clearance of early inflammatory skin lesions in 3 months . These were the first cases of successful topical tacrolimus therapy in localized scleroderma and should be regarded as a promising treatment option for LS, especially on account of its high tolerability that permits prolonged use without side-effects . Copyright John Libbey Eurotext 2003

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2003 Dec, 20(4), 586 - 9
{In vitro release of tetracycline hydrochloride from alpha-TCP cement}; Song Z et al.; Drug release from alpha-TCP cement containing tetracycline hydrochloride (TTCH) was studied in vitro . Results from X-ray diffraction study indicated that TTCH did not prevent the hydration of alpha-TCP . In vitro drug release study showed that TTCH release could sustain over 1200 h, and the release was controlled by two mechanisms: (1) diffusion of free TTCH molecules through the porous cement (square-root-of-time kinetics); (2) dissociation of TTCH from the apatite-TTCH complex (zero-order kinetics) . The mechanism controlling release would changed with the variety of the antibiotic content of cement pellets, as a result of TTCH adsorption and bonding on calcium phosphates . The first mechanism was predominantly for low concentration system TTCH-loaded apatite cement systems at the initial release period, and for high concentration TTCH-loaded apatite cement systems . As for low concentration TTCH-loaded apatite cement systems at later release stage, drug release was controlled by the coupling of the two mechanisms.

Br J Surg, 2004 Jan, 91(1), 105 - 11
Surgical site infection after groin hernia repair; Taylor EW et al.; BACKGROUND: Post-discharge surveillance for 30 days is needed to determine the true incidence of surgical site infection (SSI) . This study was undertaken to determine the incidence of, and risk factors for, SSI after hernia repair . METHODS: A total of 3150 patients who had undergone groin hernia repair in 32 Scottish hospitals were telephoned 10, 20 and 30 days after operation to screen for SSI . Patients who believed the wound to be infected were seen by a healthcare worker to confirm the diagnosis . Details of operations and risk factors were obtained by case-note review . RESULTS: One hundred and four patients (3.3 per cent) declined to give a contact telephone number, leaving 3046 patients who agreed to take part in the study . Some 108 patients (3.4 per cent) could not be contacted at any point, giving a response rate of 93.3 per cent . Complete data were available for 2665 patients (87.5 per cent); 140 (5.3 per cent) developed SSI and 57 (2.1 per cent) thought the wound infected but this was not confirmed by the healthcare worker . Patients given a prophylactic antibiotic had a lower incidence of SSI (P = 0.002), but neither increase in the American Society of Anesthesiologists grade of fitness for operation nor prolonged duration of operation was a significant risk factor for infection . CONCLUSION: SSI after hernia repair is common and large clinical trials are required to determine whether the use of prophylactic antibiotics reduces the incidence of infection .

Magy Onkol, 2003, 47(4), 403 - 8 Epub 2004 Jan 11.
{Improving results of the surgical treatment of rectal cancer in the Surgical Department of County Hospital, Szekszárd}; Zollei I et al.; The authors present that 247 elective rectal operations were performed between 1 January, 1996 and 31 December, 2001 in their surgical department . The examined 6 years were divided into a 4-year and a 2-year period . 148 operations were performed in the first and 99 in the second period . Beside personal changes, methodical and technical modifications were introduced in the second period . Distribution of age and sex was similar, and the groups were comparable . The early postoperative mortality rate decreased from 9% to 4% during the examined time . Due to the double stapling technique, the rate of anterior rectal resections has increased from 40% to 69%, and the rate of abdomino-perineal rectal extirpation has decreased from 43% to 23% . Considerable difference was found in the rate of palliative stoma-creation operations, since the 16% decreased to 8% in the second period, so the quality of life of patients has improved . The operative time, the hospital stay of the patients and the rate of operations with blood transfusion decreased . The different types of postoperative infections decreased due to the new methods.

J Hepatobiliary Pancreat Surg, 2003, 10(6), 419 - 24
Bacterial analysis of infected pancreatic necrosis and its prevention (Symposium 8: Pancreatobiliary infection (IHPBA)); Isaji S et al.; In severe acute pancreatitis, sepsis mainly due to pancreatic or peripancreatic infection have emerged as the most serious complications and now accounts for more than 80% of deaths . Collective review of organisms associated with secondary pancreatic infection in patients with acute pancreatitis has revealed that most of them are intestinal flora . Several experimental studies including ours have revealed that acute pancreatitis promotes bacterial translocation (BT), which in turn leads to infection of the pancreas and septic complications . Prophylactic antibiotics given intravenously have been demonstrated to be beneficial in reducing the rate of pancreatic infection, but their survival benefit remains unclear . We have demonstrated that continuous regional arterial infusion (CRAI) of an antibiotic is more effective than intravenous administration in preventing pancreatic infection and improving survival, in a canine model of acute necrotizing pancreatitis . Our recent experimental study has revealed that CRAI of an antibiotic via the superior mesenteric artery (SMA) is effective in mitigating intestinal mucosal damage and preventing BT in acute pancreatitis, thereby improving survival . BT aggravates pancreatic necrosis and remote organ damage in acute pancreatitis, and SMA infusion of antibiotics is effective in preventing BT and is practical for clinical use.

Curr Opin Otolaryngol Head Neck Surg, 2004 Feb, 12(1), 14 - 7
Chronic rhinosinusitis and eosinophils: do macrolides have an effect?
Wallwork B, Coman W.
PURPOSE OF REVIEW: Long-term, low-dose macrolide therapy is effective in the treatment of chronic airway inflammation . It is believed that macrolide antibiotics produce this benefit through an antiinflammatory effect that is separate from their antibiotic effect . Eosinophils are key mediators in the inflammation seen in chronic rhinosinusitis . This review discusses the effect of macrolides on eosinophilic inflammation . RECENT FINDINGS: In vitro studies recently have suggested that macrolides increase eosinophil apoptosis and reduce production of eosinophil chemotactic cytokines and adhesion molecules . In vivo studies have shown a reduction in eosinophil count and activity in asthma and chronic rhinosinusitis . Clinical response to macrolide treatment is thought to be less likely in patients with atopy . SUMMARY: In contrast to the evidence supporting the effect of macrolides on neutrophilic inflammation, there are limited data to suggest an influence on eosinophilic inflammation . For this reason, patients with prominent eosinophilic inflammation may in the future be identified as being less likely to respond to treatment . Further in vitro and clinical studies are required to investigate this subject.

Laryngoscope, 2004 Jan, 114(1), 126 - 8
Smoking in chronic rhinosinusitis: a predictor of poor long-term outcome after endoscopic sinus surgery; Briggs RD et al.; OBJECTIVE: This study was designed to determine whether smoking patients have poorer outcomes after endoscopic sinus surgery (ESS) based on a reliable validated rhinosinusitis-specific quality-of-life outcomes test . STUDY DESIGN: Retrospective chart and computed tomography (CT) review with telephone and letter questionnaire . METHODS: Charts of 230 adult patients undergoing ESS for chronic rhinosinusitis between January 1995 and December 1998 were reviewed . Each participating patient completed a detailed questionnaire, including the Sino-Nasal Outcome Test-16 (SNOT-16), at an average of 52 months after surgery . Preoperative CT scans were reviewed and the findings used to stage the patients' conditions . Multivariate analysis was used to assess these data . RESULTS: Eighty-two patients completed the questionnaire, with 26 who smoked at the time of surgery and continued to smoke at the time of answering the questionnaire (Smokers) . Average SNOT-16 score in Smokers was 27.5, versus 18.2 in those who did not smoke at the time of surgery (Non-Smokers) . There was a statistically significant correlation between elevated SNOT-16 scores and smoking (P <.001) and antibiotic use within the past year (P <.001) . There was an association between high SNOT-16 scores and both prior smoking and passive smoke exposure that did not reach statistical significance (P =.055 and P =.267, respectively) . CT staging scores and prior ESS were not statistically correlated with SNOT-16 scores . CONCLUSIONS: Smoking is associated with statistically worse outcomes after ESS based on average SNOT-16 scores . Although no investigator has proved that the effects of smoking on sinonasal health are reversible, we counsel smoking patients considering ESS about the desirability of smoking cessation (for this and many health reasons), and the possibility of a poorer postsurgery outcome should they continue smoking.

J Cataract Refract Surg, 2003 Dec, 29(12), 2452 - 4
Corneal perforation after conductive keratoplasty with previous refractive surgery; Kymionis GD et al.; A 56-year-old woman had conductive keratoplasty (CK) for residual hyperopia and astigmatism . Three years before the procedure, the patient had arcuate keratotomy, followed by laser in situ keratomileusis 2 years later for high astigmatism correction in both eyes . During CK, a corneal perforation occurred in the right eye; during the postoperative examination, an iris perforation and anterior subcapsule opacification were seen beneath the perforation site . The perforation was managed with a bandage contact lens and an antibiotic-steroid ointment; it had a negative Seidel sign by the third day . The surgery in the left eye was uneventful . Three months after the procedure, the uncorrected visual acuity was 20/32 and the best corrected visual acuity 20/20 in both eyes with a significant improvement in corneal topography . Care must be taken to prevent CK-treated spots from coinciding with areas in the corneal stroma that might have been altered by previous refractive procedures.

BMC Biotechnol . 2004 Jan 06;4(1):1.
Recombining overlapping BACs into a single larger BAC; Kotzamanis G et al.; BACKGROUND: BAC clones containing entire mammalian genes including all the transcribed region and long range controlling elements are very useful for functional analysis . Sequenced BACs are available for most of the human and mouse genomes and in many cases these contain intact genes . However, large genes often span more than one BAC, and single BACs covering the entire region of interest are not available . Here we describe a system for linking two or more overlapping BACs into a single clone by homologous recombination . RESULTS: The method was used to link a 61-kb insert carrying the final 5 exons of the human CFTR gene onto a 160-kb BAC carrying the first 22 exons . Two rounds of homologous recombination were carried out in the EL350 strain of bacteria which can be induced for the Red genes . In the first round, the inserts of the two overlapping BACs were subcloned into modified BAC vectors using homologous recombination . In the second round, the BAC to be added was linearised with the very rare-cutting enzyme I-PpoI and electroporated into recombination efficient EL350 bacteria carrying the other BAC . Recombined BACs were identified by antibiotic selection and PCR screening and 10% of clones contained the correctly recombined 220-kb BAC . CONCLUSION: The system can be used to link the inserts from any overlapping BAC or PAC clones . The original orientation of the inserts is not important and desired regions of the inserts can be selected . The size limit for the fragments recombined may be larger than the 61 kb used here and multiple BACs in a contig could be combined by alternating use of the two pBACLink vectors . This system should be of use to many investigators wishing to carry out functional analysis on large mammalian genes which are not available in single BAC clones.

Emerg Med Clin North Am, 2003 Nov, 21(4), 1075 - 87
Necrotizing soft-tissue infections; Kuncir EJ et al.; It has been more than 130 years since NSTIs were first described . Despite the development of various classification systems and progress in surgical management, these infections continue to have high mortality and pose enormous diagnostic and therapeutic challenges . For optimal outcome, treatment involves rapid institution of appropriate antibiotic coverage and early wide surgical debridement . Recovery requires aggressive resuscitation, postoperative nutritional support and wound care that is similar to the care of burn patients in many respects . The entire therapeutic process requires a well-prepared and coordinated team of health care professionals including EPs, general, orthopedic, and other specialist surgeons, infectious disease consultants, specially trained nursing staff, and physical therapists.

J Int Med Res, 2003 Nov-Dec, 31(6), 469 - 74
Comparison of H2-receptor antagonist- and proton-pump inhibitor-based triple regimens for the eradication of Helicobacter pylori in Chinese patients with gastritis or peptic ulcer; Hu FL et al.; This study compared the efficacy of an H2-receptor antagonist (H2RA)- and a proton-pump inhibitor (PPI)-based triple regimen for the eradication of Helicobacter pylori infection . Chinese patients with H . pylori-associated gastritis or peptic ulcer were randomized to receive the H2RA-based triple regimen (20 mg famotidine, 1.0 g amoxicillin and 0.4 g metronidazole) or the PPI-based triple regimen (20 mg omeprazole, 1.0 g amoxicillin and 0.4 g metronidazole) both twice daily for 1 or 2 weeks . Successful eradication of H . pylori was determined by the 13C-urea breath test and gastric mucosa histology at least 4 weeks after completion of antibiotic therapy . Eradication rates were 56.0% and 76.9% for the 1-week H2RA- and PPI-based triple regimens, respectively, and 81.6% and 82.1% for the 2-week regimens, respectively . The H . pylori eradication rate for the 2-week H2RA regimen was significantly higher than that for the 1-week regimen, but there were no significant differences between the 1- and 2-week PPI regimens . The two regimens proved equally effective in eradicating H . pylori infection.

Reprod Health Matters, 2003 Nov, 11(22), 74 - 90
Sexually transmitted infection control with sex workers: regular screening and presumptive treatment augment efforts to reduce risk and vulnerability; Steen R et al.; Sex workers have high rates of sexually transmitted infections (STIs), many of them easily curable with antibiotics . STIs as co-factors and frequent unprotected exposure put sex workers at high risk of acquiring HIV and transmitting STIs and HIV to clients and other partners . Eliminating STIs reduces the efficiency of HIV transmission in the highest-risk commercial sex contacts--those where condoms are not used . This paper reviews two STI treatment strategies that have proven effective with female sex workers and their clients . 1) Clinical services with regular screening have reported increases in condom use and reductions in STI and HIV prevalence . Such services include a strong peer education and empowerment component, emphasize consistent condom use, provide effective treatment for both symptomatic and asymptomatic STIs, and begin to address larger social, economic and human rights issues that increase vulnerability and risk . 2) Presumptive treatment of sex workers, a form of epidemiologic treatment, can be an effective short-term measure to rapidly reduce STI rates . Once prevalence rates are brought down, however, other longer-term strategies are required . Effective preventive and curative STI services for sex workers are key to the control of sexually transmitted infections, including HIV, and are highly synergistic with other HIV prevention efforts.

Rev Pneumol Clin, 2003 Nov, 59(5 Pt 1), 297 - 300
{Herpes simplex and Geotrichum candidum pneumonia in a patient with moderate renal failure}; Depagne C et al.; Viral or fungal pneumonia generally occurs in immunocompromised patients . We report a case of hypoxic pneumonia unresponsive to broad-spectrum antibiotic therapy in a patient whose only risk factor for immunodeficiency was mild silent renal failure . The causal association between Herpes simplex and Geotrichum candidum was retained on the basis of endobronchial samples and the favorable course after institution of specific treatment . It is thus useful to consider these pathogens in patients with lung infection in order to institute specific treatment.

Pancreas, 2004 Jan, 28(1), 53 - 7
The effect of combination therapy of hyperbaric oxygen, meropenem, and selective nitric oxide synthase inhibitor in experimental acute pancreatitis; Isik AT et al.; Despite the new diagnostic and therapeutic advancements, acute pancreatitis has still high rate of morbidity and mortality . We aimed to evaluate the effects of hyperbaric oxygen (HBO) therapy alone or combined with S-methylisothiourea (SMT), and meropenem (MER) therapy in an experimental rat model of acute necrotizing pancreatitis . Rats were randomly divided into 8 groups, and acute pancreatitis was induced in all groups except group 1 . Treatment protocols were saline for group 2, SMT for group 3, SMT + MER for group 4, SMT + HBO for group 5, HBO for group 6, HBO + MER for group 7, and MER for group 8 . All surviving animals were killed 48 hours after the induction of pancreatitis, and specimens were collected . Oxidative stress parameters, histopathologic scores and amylase levels were better in treatment groups than in the positive control group (group 2) . The most favorable results were obtained in HBO treatment groups, especially in HBO + MER group (group 7) . Our results indicate that adding HBO therapy to the antibiotic therapy will decrease oxidative stress parameters, serum amylase levels, and histopathological score . We suggest that adding the HBO therapy as an adjunctive to the treatment protocol of acute necrotizing pancreatitis may yield improvement in the morbidity and mortality of the disease.

Crit Care Med, 2004 Jan, 32(1), 126 - 30
Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia in intensive care units; van Nieuwenhoven CA et al.; OBJECTIVE: Although the development of ventilator-associated pneumonia (VAP) is assumed to increase costs of intensive care unit stay, it is unknown whether prevention of VAP by means of oropharyngeal decontamination is cost-effective . Because of wide ranges of individual patient costs, crude cost comparisons did not show significant cost reductions . DESIGN: Based on actual cost data of 181 individual patients included in a former randomized clinical trial, cost-effectiveness of prevention of VAP was determined using a decision model and univariate sensitivity analyses, and bootstrapping was used to assess the impact of variability in the various outcomes . DATA SOURCE: Published data on prevention of VAP by oropharyngeal decontamination, which resulted in a relative risk for VAP of 0.45, with a baseline rate of VAP of 29% among control patients . The mean costs of the intervention were 351 dollars per patient (32 dollars per patient per day) . All other costs were derived from the hospital administrative database for all individual patients . RESULTS OF BASE-CASE ANALYSIS: Prevention of VAP led to mean total costs of 16,119 dollars and 18,268 dollars for patients without preventive measures administered . Thus, costs were saved and instances of VAP were prevented . Similar results were observed in terms of overall survival . RESULTS OF SENSITIVITY ANALYSIS: Prevention of VAP remains cost-saving if the relative risk for VAP because of intervention is <0.923, the costs of the intervention are less than 2,500 dollars, and the prevalence of VAP without intervention is >4% . Bootstrapping confirmed that, with about 80% certainty, oropharyngeal decontamination results in prevention of VAP and simultaneously saves costs . In terms of a survival benefit, the results are less evident; the results indicate that with only about 60% certainty can we confirm that oropharyngeal decontamination would result in a survival benefit and simultaneously save costs . CONCLUSIONS: This study provides strong evidence that prevention of VAP by means of oropharyngeal decontamination is cost-effective.

Nucleic Acids Res, 2004 Jan 02, 32(1), 65 - 72 Print 2004.
Echinomycin inhibits chromosomal DNA replication and embryonic development in vertebrates; May LG et al.; Echinomycin, a member of the quinoxaline family of antibiotics, is known to be a strong inhibitor of RNA synthesis which has been attributed to its ability to bind to double-helical DNA . Here we study the effect of echinomycin upon DNA replication using egg extracts and embryos from Xenopus laevis as well as cultured human cells . Evidence is presented that echinomycin interferes with chromatin decondensation, nuclear assembly and DNA replication . In the absence of transcription and translation, the drug specifically blocks DNA replication in both Xenopus sperm chromatin and HeLa cell nuclei in vitro . By contrast, replication of single-stranded DNA is not inhibited indicating that echinomycin acts by interacting with the DNA and not the replication elongation proteins of chromatin . The addition of the antibiotic to HeLa cells and X.laevis embryos results in anaphase bridges and cell death . Importantly, in X.laevis embryos injected with echinomycin at the two-cell stage the drug specifically inhibits the cell cycle prior to the onset of transcription, suggesting that quinoxaline antibiotics could exert anti- proliferative effects by inhibition of chromosomal DNA replication.

Obstet Gynecol, 2004 Jan, 103(1), 86 - 91
Risk factors for febrile morbidity after hysterectomy; Peipert JF et al.; OBJECTIVE: To identify risk factors for febrile morbidity after hysterectomy for nonmalignant indications . METHODS: We performed a retrospective cohort study of 686 women who had a hysterectomy between January and September 1997 by abdominal (n = 408), laparoscopic-assisted vaginal (n = 90), or vaginal (n = 188) approaches . Potential risk factors for febrile morbidity were extracted from the medical records . By means of multivariable logistic regression, we evaluated demographic, reproductive, clinical, and operative risk factors for febrile morbidity . RESULTS: The risk of postoperative febrile morbidity in this population was 14% . Only 50% of women received prophylactic antibiotics, whereas almost 20% received no antibiotics at all, and 30% were administered antibiotics after surgical incision . Risk factors for febrile morbidity after hysterectomy, after controlling for age, body mass index, operative time, and prophylactic antibiotic administration, were abdominal approach (odds ratio 2.7; 95% confidence interval 1.6, 4.3) and blood loss at surgery of more than 750 mL (odds ratio 3.5; 95% confidence interval 1.8, 6.8) . CONCLUSION: Hysterectomy by abdominal approach and increased blood loss at the time of surgery significantly increase the risk of febrile morbidity . Preventive efforts should focus on methods to reduce postoperative febrile morbidity, including meticulous surgical technique and routine use and appropriate timing of prophylactic antibiotic therapy.

Genetics, 2003 Dec, 165(4), 1641 - 9
Amelioration of the cost of conjugative plasmid carriage in Eschericha coli K12; Dahlberg C et al.; Although plasmids can provide beneficial functions to their host bacteria, they might confer a physiological or energetic cost . This study examines how natural selection may reduce the cost of carrying conjugative plasmids with drug-resistance markers in the absence of antibiotic selection . We studied two plasmids, R1 and RP4, both of which carry multiple drug resistance genes and were shown to impose an initial fitness cost on Escherichia coli . To determine if and how the cost could be reduced, we subjected plasmid-containing bacteria to 1100 generations of evolution in batch cultures . Analysis of the evolved populations revealed that plasmid loss never occurred, but that the cost was reduced through genetic changes in both the plasmids and the bacteria . Changes in the plasmids were inferred by the demonstration that evolved plasmids no longer imposed a cost on their hosts when transferred to a plasmid-free clone of the ancestral E . coli . Changes in the bacteria were shown by the lowered cost when the ancestral plasmids were introduced into evolved bacteria that had been cured of their (evolved) plasmids . Additionally, changes in the bacteria were inferred because conjugative transfer rates of evolved R1 plasmids were lower in the evolved host than in the ancestral host . Our results suggest that once a conjugative bacterial plasmid has invaded a bacterial population it will remain even if the original selection is discontinued.

Exp Toxicol Pathol, 2003 Nov, 55(4), 247 - 50
Antioxidants suppress nitrofurazone-induced proliferation of hepatocytes; Ito K et al.; On administration to rats at a subtoxic dose, the antibiotic nitrofurazone (NF) has been shown to increase hepatocyte DNA synthesis and liver weight in a dose-dependent manner, with no histological or biochemical evidence of cell damage or necrosis . Free radicals are implicated in NF metabolism, as well as in the DNA synthesis or cell proliferation induced by a number of other chemicals . In the present study, NF was given alone or concomitantly with the antioxidants N-acetylcysteine or cyanidanol . Antioxidants prevent the effects of free radicals . Co-administration decreased hepatocyte proliferation to the same level as the control . This suppression of NF-induced hepatocyte proliferation by antioxidants therefore strongly suggests that free radical production is involved in this process.

Hosp Med, 2003 Dec, 64(12), 732 - 6
Where do we stand with chronic prostatitis? An update; Khastgir J et al.; Chronic prostatitis remains a difficult management problem, which reflects the fact that its aetiology remains incompletely understood . It is a common condition that is characterized by protracted symptoms and high morbidity . Although lacking a reliable diagnostic test, antibiotic therapy remains the mainstay of treatment in the majority of cases.

Pediatrics, 2004 Jan, 113(1 Pt 1), 54 - 8
Influence of Helicobacter pylori eradication on gastroesophageal reflux symptoms and epigastric pain in children and adolescents; Levine A et al.; OBJECTIVE: Conflicting reports have noted a possible association linking eradication of Helicobacter pylori with aggravation of gastroesophageal reflux (GER) disease . We prospectively evaluated the effect of eradication of H pylori on GER symptoms and epigastric pain and the association among these 3 parameters in a pediatric cohort . METHODS: Patients who were referred for gastroscopy were evaluated for frequency, severity, and nocturnal presence of symptoms related to GER as well as epigastric pain . Patients who were positive for H pylori received triple antibiotic therapy . The patients were followed for at least 6 months after therapy . Patients with successful eradication had symptoms compared with their pre-eradication state and were compared with a cohort of patients without H pylori or those with persistent H pylori . RESULTS: Of 119 children and adolescents who were recruited, 95 patients completed the study, with a mean follow-up of 11.2 months . The distribution of outcomes for each GER symptom (better, worse, unchanged) was similar before and after eradication and did not depend on prior H pylori status . Among patients with GER and epigastric pain, improvement in epigastric pain was significantly correlated with the improvement in GER symptoms but not with eradication of H pylori . CONCLUSIONS: Eradication of H pylori is not associated with increased symptoms of GER in children and adolescents . Improvement in epigastric pain in children is significantly correlated with the improvement in GER symptoms but not with eradication of H pylori.

Rev Esp Quimioter, 2003 Sep, 16(3), 295 - 303
{Pharmacoeconomic analysis of community-acquired pneumonia treatment with telithromycin or clarithromycin}; Rubio-Terres C et al.; A pharmacoeconomic analysis was carried out comparing the efficacy of two treatment options for community-acquired pneumonia (CAP): telithromycin and clarithromycin . It was a retrospective analysis using a decision tree model . The efficacy of the two treatment options was estimated from a randomized, double-blind clinical trial, in which 800 mg/day oral telithromycin for 10 days was compared to 1000 mg/day oral clarithromycin for 10 days in patients with CAP (162 and 156 respectively) . The use of resources was estimated based on the clinical trial and Spanish sources, and the unit costs from a Spanish health costs database . Costs were evaluated for the acquisition of antibiotic treatments, change of antibiotic due to therapeutic failure, hospital admissions, adverse reactions to treatment, primary care visits, tests and indirect costs (working days lost) . The model was validated by a panel of Spanish clinical experts . As the clinical trial was designed to show equivalence, there were no significant differences in efficacy between the treatment options (clinical cure rate 88.3% and 88.5%, respectively), and a cost minimization analysis was performed . In the base case, the average cost of the disease per patient was 308.29 euros with telithromycin and 331.5 euros with clarithromycin (a difference of 23.21 euros) . The results were stable in the susceptibility analysis, with differences favorable to telithromycin ranging between 5.50 and 45.45 euros . Telithromycin results in a cost savings of up to 45.45 euros per CAP patient compared to clarithromycin.

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