Biophys J, 2003 Apr, 84(4), 2427 - 39 Analyzing heat capacity profiles of peptide-containing membranes: cluster formation of gramicidin A; Ivanova VP et al.; The analysis of peptide and protein partitioning in lipid membranes is of high relevance for the understanding of biomembrane function . We used statistical thermodynamics analysis to demonstrate the effect of peptide mixing behavior on heat capacity profiles of lipid membranes with the aim to predict peptide aggregation from c(P)-profiles . This analysis was applied to interpret calorimetric data on the interaction of the antibiotic peptide gramicidin A with lipid membranes . The shape of the heat capacity profiles was found to be consistent with peptide clustering in both gel and fluid phase . Applying atomic force microscopy, we found gramicidin A aggregates and established a close link between thermodynamics data and microscopic imaging . On the basis of these findings we described the effect of proteins on local fluctuations . It is shown that the elastic properties of the membrane are influenced in the peptide environment. Complement Ther Med, 2003 Mar, 11(1), 33 - 8 Developing a measure of attitudes: the holistic complementary and alternative medicine questionnaire; Hyland ME et al.; We have developed an 11-item scale, the Holistic Complementary and Alternative Medicine Questionnaire (HCAMQ) . Six of the HCAMQ items relate to beliefs about the scientific validity of complementary and alternative medicine (CAM), and five to beliefs about holistic health (HH) . The HCAMQ was completed by 50 patients attending a CAM clinic and 50 attending rheumatology outpatients; the former completed it twice . Factor analysis (oblique rotation) showed that the CAM and HH items measured distinct but related constructs . The HCAMQ has good test retest reliability (r=0.86, 0.82 and 0.77 for the total, CAM subscale and HH subscale, respectively) . The individuals attending CAM clinics were significantly more positive on the CAM but not the HH subscale of the HCAMQ and also used less antibiotics than those attending rheumatology outpatients . Positivity towards CAM on the total HCAMQ and subscales was significantly associated with lower age, increased vitamin use, reduced painkiller use, and, other than on the HH subscale, less antibiotic use . The reason why the HH subscale failed to distinguish between the two patient groups or predict less antibiotic use is unknown . The HCAMQ appears to have good internal validity, but its external validity remains to be established. Curr Opin Plant Biol, 2003 Apr, 6(2), 169 - 77 Chemically regulated gene expression in plants; Padidam M; Chemically inducible systems that activate or inactivate gene expression have many potential applications in the determination of gene function and in plant biotechnology . The precise timing and control of gene expression are important aspects of chemically inducible systems . Several systems have been developed and used to analyze gene function, marker-free plant transformation, site-specific DNA excision, activation tagging, conditional genetic complementation, and restoration of male fertility . Chemicals that are used to regulate transgene expression include the antibiotic tetracycline, the steroids dexamethasone and estradiol, copper, ethanol, the inducer of pathogen-related proteins benzothiadiazol, herbicide safeners, and the insecticide methoxyfenozide . Systems that are suitable for field application are particularly useful for experimental systems and have potential applications in biotechnology. Chin Med J (Engl), 2003 Jan, 116(1), 39 - 43 Sequential non-invasive mechanical ventilation following short-term invasive mechanical ventilation in COPD induced hypercapnic respiratory failure; Wang C et al.; OBJECTIVE: To estimate the feasibility and the efficacy of early extubation and sequential non-invasive mechanical ventilation (MV) in chronic obstructive pulmonary disease (COPD) with exacerbated hypercapnic respiratory failure . METHODS: Twenty-two intubated COPD patients with severe hypercapnic respiratory failure due to pulmonary infection (pneumonia or purulent bronchitis) were involved in the study . At the time of pulmonary infection control window (PIC window) appeared, when pulmonary infection had been significantly controlled (resolution of fever and decrease in purulent sputum, radiographic infiltrations, and leukocytosis) after the antibiotic and the comprehensive therapy, the early extubation was conducted and followed by non-invasive MV via facial mask immediately in 11 cases (study group) . Other 11 COPD cases with similar clinical characteristics who continuously received invasive MV after PIC window were recruited as control group . RESULTS: All patients had similar clinical characteristics and gas exchange before treatment, as well as the initiating time and all indices at the time of the PIC window . For study group and control group, the duration of invasive MV was (7.1 +/- 2.9) vs (23.0 +/- 14.0) days, respectively, P < 0.01 . The total duration of ventilatory support was (13 +/- 7) vs (23 +/- 14) days, respectively, P < 0.05 . The incidence of ventilator associated pneumonia (VAP) were 0/11 vs 6/11, respectively, P < 0.01 . The duration of intensive care unit (ICU) stay was (13 +/- 7) vs (26 +/- 14) days, respectively, P < 0.05 . CONCLUSIONS: In COPD patients requiring intubation and MV for pulmonary infection and hypercapnic respiratory failure, early extubation followed by non-invasive MV initiated at the point of PIC window significantly decreases the invasive and total durations of ventilatory support, the risk of VAP, and the duration of ICU stay. Clin Microbiol Infect, 2003 Mar, 9(3), 239 - 41 Cure of bartonella endocarditis of a prosthetic aortic valve without surgery: value of serologic follow-up; Lesprit P et al.; Bartonella species are emerging as an important cause of blood culture-negative endocarditis, but the optimal management of this disease has not been fully defined . We describe a case of subacute Bartonella henselae endocarditis of a prosthetic aortic valve in an immunocompetent woman that was cured with long-term antibiotic therapy alone . In addition, we demonstrate that follow-up of serologic titers against B . henselae was helpful in assessing definitive cure of the infection. Fundam Clin Pharmacol, 2003 Apr, 17(2), 183 - 8 Liposomal amphotericin B in the treatment of visceral leishmaniasis in immunocompetent patients; Minodier P et al.; The leishmaniases are protozoan diseases caused by Leishmania parasites . The first-line treatment of its visceral forms is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug . Moreover antimony unresponsiveness is increasing in Leishmania infantum and L . donovani foci, 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); Gilead Science, Paris, France) seems to be less toxic than other amphotericin B lipid formulations (Amphocil); Liposome Technology Inc., Menlo Park, CA, USA, Amphotec); Ben Venue Laboratories Inc., Bedford, OH, USA) . Optimal drug regimens of AmBisome) vary from one geographical area to another . In the Mediterranean Basin, a total dose of 18 mg/kg (3 mg/kg on days 1-5 and 3 mg/kg on day 10) could be used as first-line treatment of visceral leishmaniasis in immunocompetent patients . In immunocompromised patients, especially those co-infected with HIV, relapses are frequent with AmBisome), as with other drugs. Biochemistry, 2003 Apr 8, 42(13), 3929 - 38 Histones: a novel class of lipopolysaccharide-binding molecules; Augusto LA et al.; Unlike soluble and membrane forms of lipopolysaccharide (LPS)-binding proteins, intracellular LPS-binding molecules are poorly documented . We looked for such molecules in a murine lung epithelial cell line . Two proteins with LPS-binding activity were isolated and unambiguously identified as histones H2A.1 and H4 by mass spectrometry . Synthetic peptides representing partial structures indicated that the LPS binding site is located in the C-terminal moiety of the histones . Extending the study, we found that histones H1, H2A, H2B, H3, and H4 from calf thymus are all able to bind LPS . Bindings were specific, and affinities, determined by isothermal titration calorimetry, were (except for H4) higher than that of the LPS-binding antibiotic polymyxin B . In the presence of H2A the binding of LPS to the macrophage cell line RAW 264.7, and the LPS-induced production of TNF-alpha and nitric oxide by these cells, were markedly reduced . Histones may thus represent a new class of intracellular and extracellular LPS sensors. J Int Acad Periodontol, 1999 Oct, 1(4), 121 - 6 Update on Actinobacillus Actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease; Slots J; Actinobacillus actinomycetemcomitans is an important pathogen of periodontitis in young individuals . Porphyromonas gingivalis is a major pathogen of severe adult periodontitis . A . actinomycetemcomitans and P . gingivalis can be transmitted from family member to family member and may cause periodontitis in the recipient individual . In the USA, A . actinomycetemcomitans occurs more frequently in Hispanics and Asians than in Caucasians . P . gingivalis is more common in Hispanics, Asians and Blacks than in Caucasians . A . actinomycetemcomitans and P . gingivalis strains differ in genotype, serotype, toxin and enzyme production, and cellular invasiveness . Variation in virulence may help explain differing clinical outcomes of periodontal A . actinomycetemcomitans and P . gingivalis infections . A . actinomycetemcomitans and P . gingivalis cannot be eradicated from the great majority of deep periodontal pockets by mechanical debridement alone . A . actinomycetemcomitans may be removed from subgingival sites by adjunctive systemic amoxicillin-metronidazole or other appropriate antibiotic therapies . Subgingival eradication of P . gingivalis may require periodontal surgery as well as antibiotic therapy. Rev Med Brux, 2003 Feb, 24(1), 47 - 51 {Fournier's gangrene: emergency diagnosis}; Brasseur P et al.; We present one case of Fournier's gangrene in a 56-year alcoholic patient . The source of infection was an anal fistula . Prompt diagnosis was based on CT and ultrasonography of the pelvis . An orchidectomy was performed because of testicular involvement . Fournier's gangrene is an emergency that requires early recognition to ensure therapeutic success . Treatment involves aggressive surgical debridement, broad spectrum antibiotic therapy and haemodynamic stabilization . Hyperbaric oxygen therapy may be helpful. Appl Microbiol Biotechnol, 2003 Feb, 60(6), 633 - 42 Epub 2002 Dec 18. Candicidin biosynthesis in Streptomyces griseus; Gil JA et al.; The biosynthesis of the aromatic polyene macrolide antibiotic candicidin, produced by Streptomyces griseus IMRU 3570, begins with a p-aminobenzoic acid (PABA) molecule which is activated to PABA-CoA and used as starter for the head-to-tail condensation of four propionate and 14 acetate units to produce a polyketide molecule to which the deoxysugar mycosamine is attached . Using the gene coding for the PABA synthase ( pabAB) from S . griseusIMRU 3570 as the probe, a 205-kb region of continuous DNA from the S . griseus chromosome was isolated and partially sequenced . Some of the genes possibly involved in the biosynthesis of candicidin were identified including part of the modular polyketide synthase (PKS), genes for thioesterase, deoxysugar biosynthesis, modification, transport, and regulatory proteins . The regulatory mechanisms involved in the production of candicidin, such as phosphate regulation, were studied using internal probes for some of the genes involved in the biosynthesis of the three moieties of candicidin (PKS, aromatic moiety and amino sugar) . mRNAs specific for these genes were detected only in the production medium (SPG) but not in the SPG medium supplemented with phosphate or in the inoculum medium, indicating that phosphate represses the expression of genes involved in candicidin biosynthesis . The modular architecture of the candicidin PKS and the availability of the PKSs involved in the biosynthesis of three polyene antibiotics (pimaricin, nystatin, and amphotericin B) shall make possible the creation of new, less toxic and more active polyene antibiotics through combinatorial biosynthesis and targeted mutagenesis. Eur Radiol, 2003 Apr, 13(4), 897 - 902 Epub 2002 Jun 28. Colonic involvement in non-necrotizing acute pancreatitis: correlation of CT findings with the clinical course of affected patients; Wiesner W et al.; The purpose of this study was to describe CT findings of colonic involvement in acute non-necrotizing pancreatitis and to analyze the correlation between colonic wall thickening at CT and the clinical course of these patients . The CT examinations of 19 consecutive patients with acute non-necrotizing pancreatitis who were not treated with antibiotics initially were analyzed retrospectively . The severity of acute pancreatitis was categorized according to the CT severity index (CTSI) and the presence of colonic wall thickening at the initial CT was compared with the clinical course of all patients . Seven of 11 patients with a CTSI of 4 showed a colonic wall thickening, whereas the remaining patients with a CTSI of 4 (n=4), CTSI of 3 (n=5), and CTSI of 2 (n=3) showed no colonic abnormalities at CT . Patients with colonic wall thickening presented more often with fever, showed higher levels of infectious parameters, needed more often antibiotic therapy, and had more requests for additional CT examinations and CT-guided fluid aspirations as well as a longer duration of hospital stay as compared with patients without colonic wall involvement, even if the latter presented with the same CTSI initially . It is well known that translocation of the colonic flora may significantly influence the clinical course of patients with acute pancreatitis, and our results indicate that patients with acute pancreatitis who present with colonic wall thickening at CT have an increased risk for a complicated clinical course regarding systemic infection. J Am Acad Dermatol, 2003 Apr, 48(4), 553 - 63 Cost-effectiveness analysis of tacrolimus ointment versus high-potency topical corticosteroids in adults with moderate to severe atopic dermatitis; Ellis CN et al.; BACKGROUND: Few cost-effectiveness analyses have been conducted on topical therapies for atopic dermatitis . OBJECTIVE: We sought to compare cost-effectiveness of high-potency topical corticosteroids (HPTCs) and tacrolimus ointment for the treatment of moderate to severe atopic dermatitis for patients who are not responsive to or not well controlled with mid-potency topical corticosteroids . METHODS: A Markov model represented the cyclic nature of atopic dermatitis . Clinical outcomes were derived from published literature . "Efficacy" was defined as disease-controlled days on which patients experienced a greater than 75% improvement in their disease . Resource use and changes in management were on the basis of opinions of a physician panel; secondary treatment was an oral antibiotic with topical corticosteroids . Sensitivity analyses were conducted for all variables . RESULTS: The model was sensitive to duration of continuous treatment with HPTCs . HPTCs, when limited to 2-week treatment cycles, were associated with the highest total costs ($1682 per year) and the least efficacy (185 disease-controlled days) . HPTCs in 4-week treatment intervals and tacrolimus ointment were similar in total costs and efficacy ($1317 vs $1323 for 194 vs 190 disease-controlled days, respectively) . Although primary drug costs were higher for patients treated with tacrolimus ointment, patients treated with regimens of HPTCs incurred higher secondary drug costs . CONCLUSION: In the base case analyses, tacrolimus ointment was more cost-effective than HPTCs administered in 2-week treatment cycles, and similar in cost-effectiveness to 4-week cycles of HPTCs. Eur J Clin Invest, 2003 Apr, 33(4), 340 - 5 Disruption of nasopharyngeal epithelium by pneumococci is density-linked; Lagrou K et al.; BACKGROUND: The aim of this project was to study the influence of pneumococci on nasopharyngeal epithelial integrity as a function of time and pneumococcal density . MATERIALS AND METHODS: Cell layers of an in vitro model of human nasopharyngeal epithelium were inoculated with different pneumococcal strains . The transepithelial electrical resistance (TEER), a measure of the integrity of the cell layers, and the pneumococcal concentration in the apical fluid on the epithelial cells were measured at different times after inoculation . RESULTS: Pneumococci caused a decrease in the TEER when a density of 1 x 107 CFU mL-1 was reached . The growth rate of pneumococci in our in vitro model differed between the strains tested and, for the same strain, between in vitro culture on the epithelial cells and broth culture . Differences in timing of the onset of decrease in the TEER between strains were the result of differences in growth rate on the epithelial cells . Antibiotic-induced lysis of pneumococci caused an immediate decrease in the TEER of the cell layers . CONCLUSION: Pneumococci cause a decrease in the TEER at a density of 1 x 107 CFU mL-1 . Our hypothesis is that this decrease in the TEER is the result of quorum-induced lysis of the pneumococci. Oncology (Huntingt), 2003 Mar, 17(3), 415 - 20; discussion 423-6 Management of health-care--associated infections in the oncology patient; Guinan JL et al.; Each year, 2.4 million patients in the United States develop health-care--associated infections (HAIs), requiring treatment at an annual cost of approximately $4.5 billion . HAI is the primary cause of death in approximately 30,000 patients and contributes to the death of 70,000 annually . Oncology patients are more susceptible than other patients to HAIs due to compromised immune systems, surgery (drains), invasive technology (catheters), and environmental factors . This paper will review each of these risk factors and discuss preventive steps such as a predictive index, antibiotic therapy, and infection control practices. Lancet, 2003 Mar 22, 361(9362), 1025 - 34 Amoebiasis; Stanley SL Jr; Amoebiasis is the second leading cause of death from parasitic disease worldwide . The causative protozoan parasite, Entamoeba histolytica, is a potent pathogen . Secreting proteinases that dissolve host tissues, killing host cells on contact, and engulfing red blood cells, E histolytica trophozoites invade the intestinal mucosa, causing amoebic colitis . In some cases amoebas breach the mucosal barrier and travel through the portal circulation to the liver, where they cause abscesses consisting of a few E histolytica trophozoites surrounding dead and dying hepatocytes and liquefied cellular debris . Amoebic liver abscesses grow inexorably and, at one time, were almost always fatal, but now even large abscesses can be cured by one dose of antibiotic . Evidence that what we thought was a single species based on morphology is, in fact, two genetically distinct species--now termed Entamoeba histolytica (the pathogen) and Entamoeba dispar (a commensal)--has turned conventional wisdom about the epidemiology and diagnosis of amoebiasis upside down . New models of disease have linked E histolytica induction of intestinal inflammation and hepatocyte programmed cell death to the pathogenesis of amoebic colitis and amoebic liver abscess. Unfallchirurg, 2003 Mar, 106(3), 252 - 8 {Psoas abscess after anterior spinal fusion}; Muckley T et al.; We present 3 cases of secondary psoas abscess after anterior spinal fusion . Psoas abscess is still a rare clinical entity . It is often associated with unspecific symptomatology and may present as late infection . A high index of suspicion is required for early diagnosis and treatment . Computed tomography is the imaging technology of choice . Treatment includes open abscess drainage and antibiotic therapy . In secondary psoas abscess causative treatment of the primary infection focus is essential . For psoas abscess after anterior spondylodesis this includes treatment of a deep wound infection . Predisposing factors for postoperative infection are large implants, bone grafting, long operating times, previous spinal surgery, immunodeficiency and metabolic disorders . Usually several operations are necessary to eradicate infection . As long as stability is guaranteed, implant materials should be removed . Continuing antibiotic therapy for 2-3 weeks after normalization of infectious parameters is suggested . Delayed therapy results in an increase of the morbidity and mortality of psoas abscess. Unfallchirurg, 2003 Mar, 106(3), 215 - 9 {Successful management of abdominal stab wounds with clinical evaluation: experiences of an South-African trauma unit with 496 consecutive patients}; Exadaktylos A et al.; BACKGROUND: Up to 80% of all operations performed in South African trauma units are due to penetrating injuries . This study will evaluate our own clinical guidelines for the management of penetrating abdominal injuries . METHODS: Absolute indication for operation in patients with penetrating abdominal injuries have been: haemodynamic instability, evisceration of bowels or organs, peritonitis, free air under the diaphragm on plain abdominal x-rays, the evidence of fresh blood on rectal examination or in the stomach . No ultrasonography or CT scanning has been performed . RESULTS: 496 patients were included in this study . In 248 (50%) patients an operation has been performed . 50 (20%) of them were initially selected for abdominal observation . In 230 (93%) patients, peritoneal penetration was diagnosed during laparotomy . In 18 (7%) patients the laparotomy was negative and in 24 (10%) non-therapeutic.6 (2%) patients died . Specifically 93.2% (CI 90.2-96.2%), positive prediction 92.7% (89.5%-95.7%) . CONCLUSION: The clinical evaluation of patients with abdominal stab wounds is a safe method to detect possible fatal injuries in hospitals without unlimited access to ultrasonography and CT scanning . 80% of all patients with a selective conservative approach needed no operation. Rev Med Interne, 2003 Mar, 24(3), 198 - 201 {Cutaneous metastatic Crohn's disease}; Ciubotaru V et al.; INTRODUCTION: Cutaneous metastatic Crohn's disease is a granulomatous inflammation of the skin that is noncontiguous to the gastrointestinal tract . CASE REPORT: A 42-year-old man with Crohn's disease is admitted for antibiotic resistant erysipela-like dermo-hypodermitis . The presence of granulomatous lesions on skin biopsy, the absence of any infectious agent identified despite extensive investigations and the dramatic improvement observed with corticosteroid eventually lead to the diagnosis of cutaneous metastatic Crohn's disease . CONCLUSION: During Crohn's disease, biopsy should be considered for every undiagnosed skin lesion as the characteristics of cutaneous metastatic Crohn's disease are not specific . The presence of a non caseous granulomatous dermal infiltration suggests the diagnosis and should make consider the initiation of corticosteroid and the discontinuation of others inappropriate therapeutics (i.e . surgical treatment, antibiotics). Int J Immunopathol Pharmacol, 2000 Sep, 13(3), 151 - 156 Survey of Lyme disease in Abruzzo (Italy); Fazii P et al.; This study reports the diagnostic activity for the serological diagnosis of Lyme Disease (LD) in the patients of Abruzzo, a central region of Italy . During the period from August 1994 to July 1999, serological examinations for anti-Borrelia burgdorferi antibodies were performed on 1089 samples from 769 patients with symptomatology consistent with LD . Using an immunoenzymatic technique which was confirmed with Western Blot, 29 patients were diagnosed positive . Twenty-five of these patients contracted the disease in Abruzzo, two during a trip to the USA, one was from Molise and one from Marche . Overall the patients were young, 64% were women and residents of costal areas who frequently engaged in naturalistic activities . The most common symptoms were articular and one patient presented Bannwarth Syndrome . The various antibiotic therapies used gave good results in most cases . These are the first cases reported in literature for this region and for Molise . We believe that LD is underestimated, especially due to the favorable climatic and environmental conditions present in this region . Therefore, we suggest an intensification of clinical and epidemiological controls. Biochem J, 2003 Jun 15, 372(Pt 3), 703 - 11 Daunorubicin-induced variations in gene transcription: commitment to proliferation arrest, senescence and apoptosis; Mansilla S et al.; We used a human cDNA macroarray containing various oncogenes and tumour suppressor genes to assess gene expression profiles in early-passage Jurkat T lymphocytes treated with clinically relevant concentrations of the antitumour antibiotic daunorubicin . Several oncogenes and tumour suppressor genes were either up- or down-regulated depending on the daunorubicin concentration used . The expression levels of some of these genes were confirmed by semi-quantitative reverse transcriptase-PCR . We also compared the changes in cell-cycle distribution and the apoptotic morphological characteristics of the cells treated with daunorubicin, using flow cytometry and fluorescence microscopy . Exposure to 182 nM daunorubicin (its IC(75) in Jurkat T cells: where IC(75) is the drug concentration that inhibits growth by 75%) resulted in cell-cycle arrest in G(1) and almost immediate apoptosis . In contrast, decreasing the drug concentration to 91 nM (close to the IC(50)) caused G(2) arrest and cell senescence-like growth arrest, whereas features of apoptosis and necrosis appeared only after longer incubation times . Gene expression profiles, cell-cycle distribution, the presence of DNA damage and the time-dependent response of Jurkat T cells to cell death were correlated clearly . The general behaviour of the genes suggests that cell-cycle arrest and cell death follow distinct pathways depending on drug concentration. Eur J Gastroenterol Hepatol, 2003 Apr, 15(4), 355 - 62 Drug utilization study in patients with Crohn's disease in Spain; Estiarte R et al.; OBJECTIVE: To discover the therapeutic strategies for Crohn's disease used in Spain and to analyse the factors associated with the use of each treatment . DESIGN: Observational, cross-sectional study of patients with Crohn's disease who attended hospitals in Spain . METHODS: Two structured questionnaires were used, one completed by gastroenterologists about demographic clinical data and disease activity, and the other a telephone interview with the patients to obtain epidemiological and drug utilization data . RESULTS: A total of 635 patients from 39 hospitals were included . Aminosalicylates (77%) and corticosteroids (41%) were the most commonly used drugs . Monotherapy was used in 52% of the patients and was associated with less severe disease and relapse . Aminosalicylate use was associated with relapse and associated inversely with use of immunosuppressors . Corticosteroid use was associated with relapse, disease activity, and emergency visit frequency, and associated inversely with perianal disease . Use of immunosuppressors was associated with perianal disease, chronic active disease, and routine visit frequency, and associated inversely with aminosalicylate use . Antibiotic use was associated with relapse, perianal disease, chronic active disease and hospitalization . CONCLUSION: Aminosalicylates, corticosteroids and a combination of both drugs are the drugs used most frequently against Crohn's disease in Spain . Gender, age, clinical pattern and location were not associated with the type of drug used either in monotherapy or in combined therapy. Antimicrob Agents Chemother, 2003 Apr, 47(4), 1291 - 6 Engineering anthracycline biosynthesis toward angucyclines; Metsa-Ketela M et al.; The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster . Addition of pgaF to a gene cassette that harbored the early biosynthesis genes of nogalamycin resulted in the production of two known angucyclinone metabolites, rabelomycin and its precursor, UWM6 . Substrate flexibility of pgaF was demonstrated by replacement of the nogalamycin minimal polyketide synthase genes in the gene cassette with the equivalent aclacinomycin genes together with aknE2 and aknF, which specify the unusual propionate starter unit in aclacinomycin biosynthesis . This modification led to the production of a novel angucyclinone, MM2002, in which the expected ethyl side chain was incorporated into the fourth ring. J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Mar 25, 786(1-2), 117 - 25 Cloning, expression and purification of three Chaperonin 60 homologues; Maguire M et al.; The Chaperonin 60 (Cpn60) proteins have, in addition to their well-known functions of protein folding and protection, a range of intercellular signalling activities . As part of a study to investigate the biological activity of the Cpn60 proteins, particularly from pathogenic organisms, we have cloned and expressed three Cpn60 proteins from Homo sapiens, Helicobacter pylori and Chlamydia pneumoniae . The Cpn60 proteins were purified to apparent homogeneity using a combination of nickel column affinity chromatography and Reactive Red dye affinity columns . Insoluble protein was solubilised using 8 M urea and then re-folded on the nickel column by stepwise removal of the urea . The immunostimulant LPS was removed by addition of the antibiotic polymyxin B as part of the purification process. Clin Experiment Ophthalmol, 2003 Apr, 31(2), 114 - 20 The New Zealand cataract and refractive surgery survey 2001; Elder M et al.; BACKGROUND: This study documents the current practice for cataract and refractive surgery in New Zealand . METHODS: A postal questionnaire was distributed late in 2000 to all consultant ophthalmologists in New Zealand . Most questions were identical to the 2000 survey of the American Society of Cataract and Refraction Surgeons (ASCRS) enabling a comparison . RESULTS: There was an 84% return rate from the 103 surveys distributed . In regards to cataract surgery, topical anaesthesia was used by 12% of respondents, clear corneal incisions by 64%, no suture was used by 94%, diamond blades were used by 33%, disposable blades were reused by 64%, preoperative antibiotics were used by 28%, anti-biotic was used in the irrigant by 10%, postoperative injections of steroid/antibiotics were used by 63% and 41% of patients had three postoperative visits after cataract surgery . In regards to refractive surgery, 51% of respondents had access to an excimer laser and clear lens extraction was performed by 13 ophthalmologists . Advice to a 30-year-old -7.00 myope wanting refractive surgery was to have LASIK (88%), wait (8%) or have no surgery (4%) . DISCUSSION: In broad terms, New Zealand ophthalmologists' cataract and refractive practice is similar to that of the members of ASCRS with the exception of the use of topical anaesthetic (NZ 12%vs USA 49%) and the higher use of postoperative injections of steroid and antibiotic at the end of surgery (NZ 63%vs USA 20%). Harefuah, 2003 Jan, 142(1), 5 - 9, 80 {Evaluation of the impact of a clinical pharmacist on the quality and cost of pharmacotherapy in a general surgical department, the Hillel-Yaffe Medical Center}; Schwartzberg E et al.; BACKGROUND: Clinical pharmacy could be defined as an umbrella of services aimed at maximizing the pharmacotherapeutic effect, minimizing the risk for developing adverse drug effects and reducing drug expenditures for the health care system . Clinical pharmacists, in Israel and abroad, have been practicing in different health care settings aiming to implement the principles mentioned above . Most of the articles previously published reviewed the role of the clinical pharmacist in internal medicine wards or in intensive care units . This article focuses on the role of the clinical pharmacist in a general surgery department and the influence of this service on the quality and cost of pharmacotherapy and on intravenous antibiotic therapy in particular . AIMS: Improving the quality of pharmacotherapy while optimally using economic resources in a general surgery ward . METHODS: During September 1999 to August 2000, the clinical pharmacist joined physician rounds in the surgical ward . During the rounds he advised physicians about clinical and economical aspects of drug treatment, and collected data on his activity on a specific designated form . The data was processed on a central computerized database, and analyzed to determine the influence of the clinical pharmacist on clinical and economical outcomes . RESULTS: At the end of the study period the following were found: The pharmacist made 219 interventions . These included adverse drug effects, which were identified and/or prevented . When considering the economic data, a substantial reduction of 56% in intravenous antibiotic therapy was noted (direct saving of about 140,000 NIS) . Such savings were accompanied by changes in the prescribing patterns in the department, which were translated into increased rate of oral antibiotic prescribing and reduction in the use of certain i.v . antibiotics while undamaging the quality of the pharmacotherapeutic effect . CONCLUSION: The results of this study indicate that participation of a clinical pharmacist during physicians rounds improved the quality of the pharmacotherapy, assisted in changing clinicians prescribing habits, and at the same time significantly reduced the direct expenditures on medications in general and of intravenous antibiotic therapy in particular. Chirurg, 2003 Mar, 74(3), 244 - 7 {Extrahepatic portal vein thrombosis following laparoscopic cholecystectomy}; Rusznak M et al.; Postoperative portal vein thrombosis is a rare complication, which occurs most often after hepatic surgery, but has not yet been described in combination with laparoscopic cholecystectomy . We present a case where thrombotic occlusion of the portal vein was diagnosed on the 6th day following laparoscopic cholecystectomy . Treatment with high-dose anticoagulant and antibiotic therapy was successful and without further complications. Khirurgiia (Mosk), 2003, (1), 9 - 11 {Prevention of purulent complications after reconstructive vascular operations in elderly and aged patients}; Aslanov AD et al.; Results of surgical treatment of 382 patients with III-IV stages critical limb ischemia and concomitant diseases were analyzed . The mean age of the patients was 67.7 years . All the patients underwent reconstructive operations on lower limbarteries . Three variants of antibiotic therapy were compared: 1) antibiotics were administered parenterally; 2) they were injected endolymphatically; and 3) they were used parenterally and endolymphatically . Combined antibiotic, i.e . a combination of parenteral and endolymphatic routes of administration was most effective. Nihon Kokyuki Gakkai Zasshi, 2002 Nov, 40(11), 875 - 83 {Legionella pneumonia: report of 25 community-acquired cases}; Takayanagi N et al.; We assessed clinical, laboratory and radiologic findings in 25 patients (21 men and 4 women; mean age 60.1 years) with Legionella pneumonia . The diagnosis was confirmed from the isolation of Legionella pneumophila in respiratory samples(nine cases), or by a fourfold increase or decrease in antibody titers in the paired serum samples (16 cases) . Twelve patients were smokers, 5 patients were chronic alcoholics and 18 patients had underlying diseases . Regarding severity, the illnesses were mild (three patients), moderate (seven patients) and severe (fifteen patients) . The following presenting symptoms and findings that characterize Legionella pneumonia were seen: a temperature of more than 40 degrees C (six patients), disorientation or gate disturbances(ten patients), diarrhea (eight patients), relative bradycardia(eight patients), hyponatremia(five patients), and a high creatinine phosphokinase suggesting rhabdomyolysis(five patients) . Rapid progression of infiltrates on chest radiographs before appropriate antibiotic therapy was observed in seven of the twelve patients whose previous chest films were available . Only one patient, who was in endotoxin shock on admission, died . Suspected sources of infection for 13 patients were a hot spring and a public bath . We conclude that a detailed analysis of the above clinical features makes possible the diagnosis of Legionella pneumonia. Ann Thorac Surg, 2002 Dec, 74(6), 2184 - 6 Endovascular management of a ruptured mycotic aneurysm of the innominate artery; Bush RL et al.; Mycotic aneurysms of the innominate artery are infrequent lesions and, as such, represent challenging surgical problems . We describe herein a case of a ruptured mycotic innominate artery aneurysm, which developed after radical neck dissection and radiation therapy for tonsillar carcinoma . The aneurysm was successfully excluded from the systemic circulation with endoluminal placement of a covered stent, with efficacy confirmed by vascular imaging at 6 months follow-up . The patient suffered no permanent neurologic sequelae . Long-term follow-up and chronic antibiotic therapy will be necessary to avoid infection of the covered stent in this high-risk surgical patient. Spine, 2003 Mar 15, 28(6), E106 - 13 Psoas abscess: the spine as a primary source of infection; Muckley T et al.; STUDY DESIGN: Case report, literature review, discussion . OBJECTIVES: To emphasize the role of the spine as primary source of infection for psoas abscess . SUMMARY OF BACKGROUND DATA: Spine-associated psoas abscesses increase with more frequent invasive procedures of the spine and recurring tuberculosis in industrialized countries . Diagnosis is often delayed by misinterpretation as arthritis, joint infection, or urologic or abdominal disorders . METHODS: We present six cases of psoas abscesses associated with spinal infections that were treated in our hospital from January to December 2001 . Diagnostic and treatment concepts are discussed . RESULTS: Our data emphasize the importance of the spine as primary source of infection and suggest an increase in the incidence of secondary psoas abscess . Treatment includes open surgical drainage and antibiotic therapy . In patients with high operative risk and uniloculated abscess, a CT-guided percutaneous abscess drainage can be sufficient . It is essential to combine abscess drainage with causative treatment of the primary infectious focus . Related to the spine, this includes treatment of spondylodiscitis or implant infection after spinal surgery . Usually, several operations are necessary to eradicate bone and soft-tissue infection and restore spinal stability . Continuous antibiotic therapy over a period of 2-3 weeks after normalization of infectious parameters is recommended . CONCLUSION: The spine as primary source of infection for secondary psoas abscess should always be included in differential diagnosis . Because the prognosis of psoas abscess can be improved by early diagnosis and prompt onset of therapy, it needs to be considered in patients with infection and back or hip pain or history of spinal surgery. Aliment Pharmacol Ther, 2003 Mar 15, 17(6), 799 - 805 Effect of treatment of Helicobacter pylori on the prevention of gastroduodenal ulcers in patients receiving long-term NSAIDs: a double-blind, placebo-controlled trial; Lai KC et al.; BACKGROUND: There is controversy as to whether Helicobacter pylori and non-steroidal anti-inflammatory drugs interact to cause peptic ulcers . AIM: To study whether the eradication of H . pylori in patients on long-term non-steroidal anti-inflammatory drug therapy prevents the development of ulcers . METHODS: Patients infected with H . pylori whilst receiving long-term non-steroidal anti-inflammatory drug therapy, but with no ulcers at baseline endoscopy, were randomized to receive either triple antibiotic therapy (metronidazole 300 mg, clarithromycin 250 mg and amoxicillin 500 mg, given four times daily; n = 70) or placebo (n = 70) for 2 weeks . Non-steroidal anti-inflammatory drugs were continued throughout the study period . Endoscopy was repeated 12 weeks after the end of treatment . The development of ulcers was compared between the two groups . RESULTS: Endoscopy at 12 weeks revealed peptic ulcer development in five {7%; 95% confidence interval (CI), 2-16} of the patients who received triple therapy and in six (9%; 95% CI, 3-18) of those who received placebo (P = 1.00) . No significant difference in the development of ulcers was found between patients with persistent H . pylori infection (7/80; 9%; 95% CI, 4-17) and those with the eradication of H . pylori (4/52; 8%; 95% CI, 2-19) (P = 1.00) . CONCLUSIONS: The eradication of H . pylori in patients receiving long-term treatment with non-steroidal anti-inflammatory drugs did not prevent ulcer development . However, because the rate of ulcer development was low, a study with a larger sample size is required to confirm this finding. Z Kardiol, 2002, 91 Suppl 3, 49 - 57 Sirolimus-eluting stents: a review of experimental and clinical findings; Toutouzas K et al.; Sirolimus (rapamycin), a macrolide antibiotic with known potent immunosuppressive properties, acts in the first phase (G1) of the cell cycle, blocking its further progression to the phase of DNA synthesis (S) . In experimental models, rapamycin is effective in inhibiting smooth muscle cell proliferation and migration after vessel wall injury with balloon angioplasty . These results lead to the clinical application of sirolimus-eluting stents in 45 patients in Sao Paulo and Rotterdam (FIM Registry) and 238 patients in a randomized, European multicenter trial (RAVEL) . These trials showed, by angiography and intravascular ultrasound, almost complete abolition of in-stent late hyperplasia up to one year after the procedure . In this review, we describe the experimental and clinical results of sirolimus-eluting stents including our experience of 26 stents implanted in 17 patients . In elective de novo lesions has shown remarkably clear lumens at follow-up angiography and intravascular ultrasound within the stented segments were observed with no lesion progression at the stent margins or thrombosis after a 2 month regimen of aspirin, and ticlopodine or clopidogrel . New large-scale ongoing clinical trials will investigate the efficacy of sirolimus-eluting stents in lesions that are traditionally associated with high restenosis rates after stent implantation, such as long lesions, bifurcations and instent restenosis. Radiographics, 2003 Mar-Apr, 23(2), 359 - 72 Imaging of complications of acute mastoiditis in children; Vazquez E et al.; Acute mastoiditis is a serious complication of acute otitis media in children . Suppurative disease in the mastoid region occasionally spreads to the adjacent dura mater of the posterior and middle cranial fossae and the sigmoid sinus by means of thrombophlebitis, osseous erosion, or anatomic pathways, producing intracranial complications . Computed tomography (CT) should be performed early in the course of the disease to classify the mastoiditis as incipient or coalescent and to detect intracranial complications . On the basis of the clinical features and imaging findings, the disease is managed conservatively with intravenously administered antibiotics or treated with mastoidectomy and drainage plus antibiotic therapy . CT is therefore a decisive diagnostic tool in determining the type of therapy . In addition, magnetic resonance imaging is performed in patients with clinical symptoms or CT findings suggestive of intracranial complications because of its higher sensitivity for detection of extraaxial fluid collections and associated vascular problems . Copyright RSNA, 2003 J Protein Chem, 2002 Nov, 21(8), 505 - 14 Use of amphotericin B as optical probe to study conformational changes and thermodynamic stability in human serum albumin; Romanini D et al.; The binding of polyene antibiotic amphotericin B to serum albumin was studied using absorption, fluorescence, and circular dichroism techniques . A hypochromic effect was observed in the absorption spectrum of amphotericin B in the presence of albumin with maxima at 366 nm, 385 nm, and 408 nm, which correspond to the absorption of the monomeric form of amphotericin B . A modification on the circular dichroism spectrum of amphotericin B in the presence of albumin was observed at bands 329 nm and 351 nm (excitronic interaction), which suggests that only amphotericin B monomer is bound to the protein . Amphotericin B perturbs the specific markers for sites I, II, and fatty acid binding site bound to these sites, suggesting that amphotericin B interacts with a great binding area in albumin . Lysines 199 and 525 in albumin participate in the molecular interaction between amphotericin B and the protein . The absorption spectrum of amphotericin B bound to albumin was sensitive to the chemical and thermal treatment of the protein, to neutral-basic transition of albumin and to conformational changes induced by the binding of other ligands to this protein. Med Princ Pract, 2003 Apr-Jun, 12(2), 129 - 32 Pediatric idiopathic pulmonary hemosiderosis diagnosed by sputum analysis: plain radiography and computed tomography findings; Kocakoc E et al.; OBJECTIVE: Idiopathic pulmonary hemosiderosis (IPH) is an uncommon disorder, which is characterized by recurrent hemoptysis, iron deficiency anemia and diffuse parenchymal infiltration on chest radiographs in pediatric patients . We wish to present clinical and radiological (plain radiography and CT) findings of this rare pathology . CLINICAL PRESENTATION AND INTERVENTION: A 14-year-old girl was admitted to the pediatric emergency department with complaints of cough, dyspnea, fatigue and bloody sputum for 6 months . She had been hospitalized 3 times during this period and received antibiotics and blood transfusion . Chest X-rays revealed prominent perihilar and bibasilar consolidation . CT showed a ground glass pattern and consolidated areas with increased density . Sputum analysis yielded hemosiderin-laden macrophages . With presumptive diagnosis of IPH, prednisolone was administered . Her symptoms improved on the 5th day of treatment and 1 month later, plain chest radiography demonstrated marked improvement . CONCLUSION: Although IPH is a rare condition, the diagnosis of IPH should be considered, among others, in a patient with hemoptysis and bilateral infiltration in the chest X-ray . This may prevent antibiotic misuse and risk of death due to severe hemorrhage . Arch Facial Plast Surg, 2003 Mar-Apr, 5(2), 175 - 9 Cleft lip nasal reconstruction using porous high-density polyethylene; Romo T 3rd et al.; BACKGROUND: The multitude of factors involved with a unilateral cleft lip nasal defect has spurred various surgical techniques in the past . Recently, synthetic materials have been introduced for use in nasal reconstruction . OBJECTIVE: To report on and illustrate the use of porous high-density polyethylene implants in cleft lip nasal reconstruction . DESIGN: A retrospective review of cleft lip nasal reconstruction using porous high-density polyethylene in patients with a unilateral cleft lip defect from January 1, 1993, through June 30, 2000 . SETTING: Facial plastic surgery private practice . PATIENTS: Eighteen patients with a unilateral cleft lip without a history of formal rhinoplasty . INTERVENTIONS: All 18 patients required multiple implants, including a columellar strut, premaxillary and prealveolar plumper grafts, a dorsal tip implant, and a unilateral nasal valve batten, using the open rhinoplasty approach . RESULTS: Favorable aesthetic results, as judged by one of us (T.R.), were achieved in all patients . All implants were well tolerated . Postoperative follow-up ranged from 6 months to 7 years . A complication occurred in 1 patient (6%), which resolved with removal of a single implant and intravenous antibiotic therapy . No other complications, including skin erosion or implant extrusion, have been noted . CONCLUSIONS: Porous high-density polyethylene implants for cleft lip nasal reconstruction are well tolerated and achieve good aesthetic results . Porous high-density polyethylene implants lend stability through fibrovascular ingrowth, with integration of the implants to the surrounding tissue. Chir Ital, 2003 Jan-Feb, 55(1), 73 - 6 Pelvic actinomycosis masquerading as malignancy: report of two cases and review of the literature; Mavor E et al.; Pelvic actinomycosis is uncommon, presenting most frequently as an abdominal mass and simulating advanced malignancy in female patients with a past history of intrauterine contraceptive use . It responds favourably to prolonged antibiotic therapy with occasional need for abscess drainage and debridement or ureteric stenting . Incorrect diagnosis may result in overly invasive investigations and unnecessarily radical extirpative surgery. Masui, 2003 Jan, 52(1), 58 - 63 {Septic shock associated with pyogenic liver abscess rescued with percutaneous transhepatic abscess drainage}; Mizuno J et al.; We report a case of septic shock associated with pyogenic liver abscess rescued with percutaneous transhepatic abscess drainage (PTAD) . A 70-year-old male patient was admitted to our outpatient department of internal medicine with general fatigue, dullness of bilateral shoulders and extremities, appetite loss, weight loss, headache, and vertigo . Laboratory tests showed severe inflammatory indications, anemia, and high values of hepatobiliary enzymes and blood sugar . Abdominal ultrasonography and enhanced CT showed a pyogenic liver abscess of 10 cm in diameter at S 6-7 in the right hepatic lobe . The patient's condition deteriorated suddenly that night . From the results of abdominal ultrasonography and enhanced CT, we made diagnosis of septic shock associated with pyogenic liver abscess . Emergency abdominal ultrasound-guided PTAD was performed under local anesthetic . Postoperatively, the antibiotic was infused daily through a PTAD tube into the liver abscess space . He recovered and his laboratory tests improved gradually . On abdominal ultrasonography and enhanced CT, the liver abscess disappeared by 19th postoperative day, and PTAD tube was removed . There was no complication during PTAD treatment . We conclude that patients in septic shock should undergo further examinations immediately and treatment of the infected tissue should be started as soon as possible . PTAD may be an additional effective procedure for pyogenic liver abscess in septic shock . Furthermore, local antibiotic lavage through a PTAD tube into the liver abscess space may be an important supplementary method in the management of the illness. J Biomed Mater Res B Appl Biomater, 2003 Apr 15, 65(1), 137 - 49 Tobramycin and gentamycin elution analysis between two in situ polymerizable orthopedic composites; DiCicco M et al.; This research analyzed Tobramycin and Gentamycin elution characteristics for two antibiotic-impregnated bone composites: PMMA-based Simplex P and the novel, hybrid, bioactive, CORTOSS . Experimental results were correlated with composite hydrophilicity and antibiotic phase partitioning behaviors . The phase partitioning experiment was conducted to understand antibiotic solubility in aqueous environments . By comparing experimental results with calculated data, antibiotic release behavior was predicted . Total Tobramycin elution percentages from CORTOSS and Simplex P were 12.5 and 6.4%, respectively . Total Gentamycin elution percentages from CORTOSS and Simplex P were 6.95 and 10.17%, respectively . Phase partitioning data indicate 100% of Tobramycin remains in aqueous phases, being extremely hydrophilic . This is supported by its calculated theoretical value (log P = - 7.32) . Results suggest that Tobramycin elution can be attributed to composite hydrophilicity as well as its high degree of hydrophilicity . Fifteen percent of Gentamycin distributes in hydrophobic phases (log P = - 4.22) . Despite a lower Gentamycin hydrophilicity, its release was affected by its complexation with polar salts in the leaching buffer, thereby increasing its elution potential, making it appreciably water soluble . CORTOSS is more hydrophilic; therefore the migration of aqueous liquids into the polymer network of CORTOSS facilitates greater antibiotic elution compared with hydrophobic Simplex P . Mol Biol Cell, 2003 Mar, 14(3), 1204 - 20 Tor kinases are in distinct membrane-associated protein complexes in Saccharomyces cerevisiae; Wedaman KP et al.; Tor1p and Tor2p kinases, targets of the immune-suppressive antibiotic rapamycin, are components of a highly conserved signaling network that couples nutrient availability and cell growth . To gain insight into the molecular basis underlying Tor-dependent signaling, we used cell fractionation and immunoaffinity chromatography to examine the physical environment of Tor2p . We found that the majority of Tor2p associates with a membrane-bound compartment along with at least four other proteins, Avo1p-Avo3p and Lst8p . Using immunogold electron microscopy, we observed that Tor2p, as well as Tor1p, localizes in punctate clusters to regions adjacent to the plasma membrane and within the cell interior, often in association with characteristic membranous tracks . Cell fractionation, coimmunoprecipitation, and immunogold electron microscopy experiments confirmed that Lst8 associates with both Tor2p as well as Tor1p at these membranous sites . In contrast, we find that Kog1, the yeast homologue of the mammalian Tor regulatory protein Raptor, interacts preferentially with Tor1p . These findings provide evidence for the existence of Tor signaling complexes that contain distinct as well as overlapping components . That these complexes colocalize to a membrane-bound compartment suggests an intimate relationship between membrane-mediated signaling and Tor activity. Hinyokika Kiyo, 2003 Jan, 49(1), 25 - 7 {A case of psoas abscess with ureteral stone}; Komori K et al.; A 62-year-old diabetic woman with right hydronephrosis was referred to our department, presenting right back pain and high fever . A ureteral stone with right hydronephrosis was pointed on DIP . Although the calculus was removed by extracorporeal shock wave lithotripsy, persistent high fever continued . Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed a mass in the retroperitoneal space . Purulent fluid with a negative cytology was acquired by percutaneous biopsy following ultrasonography-guided percutaneous drainage . The postoperative course was uneventful with antibiotic therapy. BJOG, 2003 Mar, 110(3), 267 - 71 The Haven: a pilot referral centre in London for cases of serious sexual assault; Kerr E et al.; OBJECTIVE: Several schemes have been reported to improve treatment of rape and to encourage reporting . The development of a comprehensive forensic and follow up service for complainants of sexual assault is described, and activities of the first year are reviewed . DESIGN: Retrospective review of case records of complainants examined in The Haven . SETTING: Department of Sexual Health in a London teaching hospital . SAMPLE: All case records, 676 complainants, from the first year of cases seen in The Haven . METHODS: Description of setting up a service in partnership between the National Health Service and the Metropolitan Police, called The Haven . Analysis of a standardised proforma used for case records . RESULTS: Mean age of complainants is 26 years (range 11-66); 6% were male . Assailant was categorised as a stranger in 52% of cases; attack involved physical violence in 50% of cases; 24% of victims had genital injuries; 39% had other physical injuries . Immediate care given at time of forensic examination included 30% of women receiving emergency contraception and 5% of clients receiving post-exposure prophylaxis against HIV . Fifty-five percent of clients returned for a sexual health screen and/or counselling . Thirty-one percent received screening for sexually transmitted infections and 12% were diagnosed with one or more infections . CONCLUSIONS: Requirements following sexual assault include forensic examination, first aid, postcoital contraception, prevention and management of sexually transmitted infections and psychosocial support . Provision of these services within a sexual health setting is feasible. An Pediatr (Barc), 2003 Jan, 58(1), 39 - 44 {Complementary therapies in cystic fibrosis: evidence of therapeutic benefits and treatment recommendations}; Salcedo Posadas A et al.; Cystic fibrosis (CF) is an autosomal-recessive disorder that predominantly affects the respiratory system . When this disease was described in 1938 the mortality rate was approximately 70 % in the first year of life . Survival has dramatically increased from a median of approximately 4 years in the 1960s to 19 years in the 1970s and 33 years in 2001 according to figures from the American Cystic Fibrosis Foundation . This impressive increase in the life expectancy of individuals with CF is undoubtedly related to recent advances in the organization of specialized CF units and to the use of new therapies against respiratory involvement.The traditional basis of treatment for CF lung disease includes nutritional support, antibiotic therapy, chest physical therapy and aerobic exercise . Preventive measures such as influenza vaccination and avoidance of tobacco smoke are also useful . Several new approaches such as ion transport therapy, protein therapy and gene therapy are currently being developed.Many studies have provided clear evidence of the therapeutic benefits of antibiotics, respiratory physiotherapy, exercise, and nutrition.In this article we review the scientific evidence on the advantages of the use of several therapeutic interventions against inflammation, increased sputum viscoelasticity and adhesiveness, and bronchial obstruction in CF patients. Clin Infect Dis, 2003 Mar 15, 36(6), 803 - 11 Epub 2003 Mar 04. Electronic human immunodeficiency virus (HIV) clinical reminder system improves adherence to practice guidelines among the University of Washington HIV Study Cohort; Kitahata MM et al.; We conducted a prospective study of an electronic clinical reminder system in an academic medical center-based human immunodeficiency virus (HIV) specialty clinic . Published performance indicators were used to examine adherence to HIV practice guidelines before and after its implementation for 1204 patients . More than 90% of patients received CD4 cell count and HIV type 1 (HIV-1) RNA level monitoring every 3-6 months during both time periods, and approximately 80% of patients with a CD4 cell count nadir of <350 cells/mm(3) received highly active antiretroviral therapy . Patients were significantly more likely to receive prophylaxis against Mycobacterium avium complex (hazard ratio, 3.84; 95% confidence interval {CI}, 1.58-9.31; P=.003), to undergo annual cervical carcinoma screening (OR, 2.09; 95% CI, 1.04-4.16; P=.04), and to undergo serological screening for Toxoplasma gondii (odds ratio {OR}, 1.86; 95% CI, 1.05-3.27; P=.03) and syphilis infection (OR, 3.71; 95% CI, 2.37-5.81; P<.0001) . HIV clinical reminders delivered at the time that HIV care is provided were associated with more timely initiation of recommended practices. Arthroscopy . 2003 Mar;19(3):E26. Septic arthritis caused by Erysipelothrix rhusiopathiae infection after arthroscopically assisted anterior cruciate ligament reconstruction; Allianatos PG et al.; A case of septic arthritis caused by Erysipelothrix rhusiopathiae, after an arthroscopically assisted anterior cruciate ligament (ACL) substitution in a non-immunosuppressed patient is described . An 18-year-old man underwent an ACL reconstruction with a quadruple hamstring graft . Eight days postoperatively, the patient developed fever, knee pain, and effusion without erythema or suppuration . He was readmitted to the hospital with the diagnosis of septic arthritis . The patient's erythrocyte sedimentation rate, C-reactive protein level, and white blood cell count were high . The joint was aspirated and the fluid was sent for cultures that revealed the presence of E rhusiopathiae . E rhusiopathiae is widespread in nature, it is transmitted by direct cutaneous laceration, and it causes septic arthritis, meningitis, endocarditis, and renal failure in immunosuppressed people with poor prognosis . In our case, the infection was treated with arthroscopic lavage and debridement, retention of the graft and hardware, and intravenous antibiotic administration for 6 weeks, followed by oral administration for 16 weeks. Crit Care Med, 2003 Mar, 31(3), 812 - 7 Bronchoalveolar interleukin-1 beta: a marker of bacterial burden in mechanically ventilated patients with community-acquired pneumonia; Wu CL et al.; OBJECTIVE: To assess the relationship between concentrations of bronchoalveolar cytokines and bacterial burden (quantitative bacterial count) in intubated patients with a presumptive diagnosis of community-acquired pneumonia . DESIGN: A cross-sectional and clinical investigation.SETTING Medical/surgical and respiratory intensive care unit of a tertiary 1,200-bed medical center . PATIENTS: According to the time course of community-acquired pneumonia at the time of study with bronchoalveolar lavage, 69 mechanically ventilated patients were divided into three subgroups: primary (n = 11), referral (n = 23), and treated (n = 35) community-acquired pneumonia . INTERVENTIONS: Bronchoalveolar lavage was performed in the most abnormal area on chest radiograph by fiberoptic bronchoscope . Bronchoalveolar lavage fluid was processed for quantitative bacterial culture . The concentrations of bronchoalveolar lavage cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, and interleukin-10) also were measured . MEASUREMENTS AND MAIN RESULTS: Thirty-two patients had a positive bacterial culture (bronchoalveolar lavage > or = 10 colony-forming units/mL)., and made up 76% of pathogens recovered at high concentrations . The concentrations of bronchoalveolar lavage interleukin-1 beta were 199.1 +/- 32.1 and 54.9 +/- 13.0 pg/mL (mean +/- se) in the patients with positive and negative bacterial culture, respectively (p < .001) . Bronchoalveolar lavage interleukin- 1 beta was significantly higher in the patients with a high bacterial burden (p < .001), with mixed bacterial infection (p < .001), and with pneumonia (p < .001), compared with values in patients without these features . The relationship between bacterial load and concentrations of bronchoalveolar lavage interleukin-1 beta was very strong in the patients with primary and referral community-acquired pneumonia but was borderline in treated community-acquired pneumonia . CONCLUSIONS: The common pathogens were similar to the core pathogens of hospital-acquired pneumonia, probably due to antibiotic effects, delayed sampling, and superimposed nosocomial infection . Since the concentration of bronchoalveolar lavage interleukin-1 beta was correlated with bacterial burden in the alveoli, it may be a marker for progressive and ongoing inflammation in patients who have not responded to pneumonia therapy and who have persistence of bacteria in the lung. Tissue Eng, 2003 Feb, 9(1), 27 - 36 Modulation of the contractile and biosynthetic activity of chondrocytes seeded in collagen-glycosaminoglycan matrices; Lee CR et al.; Studies have demonstrated that articular chondrocytes can express the gene for alpha-smooth muscle actin (SMA) and can contract porous polymeric matrices employed for tissue engineering, thereby altering the pore structure and distorting the shape of the scaffold . The objectives of this study were to determine whether an agent known to disrupt microfilament organization in chondrocytes could reduce this contractility and to assess whether there was an association between the contractile behavior of chondrocytes and their biosynthetic activity . Staurosporine, an antibiotic known to inhibit protein kinase C and disrupt cytoskeletal structure, was used as the agent to modulate the chondrocytic phenotype and contractile and biosynthetic activity of serially passaged adult canine chondrocytes seeded in type 1 collagen-glycosaminoglycan scaffolds . Cells in monolayer culture treated with as little as 3 nM staurosporine for 4 days contained type II procollagen, whereas few cells in the untreated control cultures demonstrated type II procollagen synthesis . Treatment with staurosporine also led to a decrease in the amount of SMA synthesized by the cells . Consistent with this decreased expression of the contractile actin isoform, cells cultured in the collagen-glycosaminoglycan scaffolds and treated with 5 nM staurosporine contracted the scaffold significantly less than untreated cells (15% diameter contraction by treated cells, compared with more than 50% contraction by untreated cells) . The staurosporine-treated cells were biosynthetically active, displaying higher rates of protein and glycosaminoglycan synthesis, as indicated by rates of incorporation of {(3)H}proline and {(35)S}sulfate, respectively, compared with untreated cells . The long-held notion that changes in cytoskeletal structure influence phenotypic characteristics of cultured chondrocytes may now be extended to relate expression of a specific muscle actin isoform to certain cell processes . Moreover, the finding that chondrocytes with a lower level of expression of SMA and reduced contractility display higher rates of biosynthesis warrants further study. East Afr Med J, 2002 Sep, 79(9), 476 - 9 Chlamydia as a cause of late neonatal pneumonia at Kenyatta National Hospital, Nairobi; Were FN et al.; BACKGROUND: Neonatal pneumonia is a common cause of morbidity and mortality all over the world . The problem is known to be higher in resource poor third world countries . Organisms (such as chlamydia) not covered by routine laboratory tests and regular antibiotic regimes may frequently contribute towards the causation of late neonatal pneumonia . It is therefore useful to gather epidemiological evidence to guide in the routine diagnosis and treatment of such infections . OBJECTIVE: To determine the prevalence of chlamydia associated pneumonia among infants developing the disease between the 7th and 30th days of life (late neonatal pneumonia) . DESIGN: Cross sectional survey . SETTING: Newborn Unit, Kenyatta National Hospital . SUBJECTS: Fifty two newborns clinically diagnosed as having late neonatal pneumonia . They were all subjected to chest X-rays to confirm the clinical diagnosis . Nasopharyngeal aspirates for chlamydia antigen detection tests were then performed on all patients . The study was undertaken during the months of September through to November 2000 . MAIN OUTCOME MEASURES: The proportion of newborns with late neonatal pneumonia that have chlamydia trachomantis as the sole or contributory causative agent . RESULTS: Fifty two newborns of postnatal age between seven and 30 days were recruited . Their sex distribution was about 1:1 . Thirty three (63.5%) of these infants were found with chlamydia in their upper airways . Thirty out of 47 available chest X-rays, representing 63.8% had evidence of interstitial pneumonitis . Chlamydia associated pneumonia indicated by the presence of both interstitial pneumonia and colonization of the upper air ways was present in 24 out of 47 patients, 51% of the total cases of late neonatal pneumonia . When X-rays alone were compared with our gold standard for the diagnosis of chlamydia pneumonia (radiology and colonization), we computed a sensitivity of 100%, specificity 73%, negative predictive value 100% and positive predictive value of 80% . Mode of delivery, birth weight and gestation had no association with nasopharyngeal colonization by chlamydia or actual diagnosis of chlamydia pneumonia . CONCLUSION: The prevalence of chlamydia associated infection among newborns with late neonatal pneumonia at Kenyatta National Hospital is 51%, eight times more than that reported elsewhere . Chest X-rays appear to be a reliable diagnostic tool in this group . The use of antichlamydial drugs in addition to the regular antibiotics whenever a diagnosis of late neonatal pneumonia is made is justifiable. Prog Cardiovasc Nurs, 2003 Winter, 18(1), 42 - 9 The role of infection in the pathogenesis of cardiovascular disease; Zebrack JS et al.; Atherosclerosis is a complex, multifactorial disease . Recently, research has intensified to identify the role of various infections in the pathogenesis of atherosclerosis . Specific agents have been proposed as direct initiators or accelerators of atherosclerosis, while other infectious agents have been proposed as accelerators of atherosclerosis through nonspecific stimulation of the inflammatory cascade . Recently, the total pathogen burden concept has suggested that while each specific infection contributes only slightly to the pathogenesis of atherosclerosis, the cumulative effects of infectious agents contribute greatly . Several randomized trials evaluating antibiotic therapy in the prevention of cardiovascular events have now been completed, although results have been conflicting . This manuscript summarizes current understanding of the role of infectious agents as a trigger of inflammation, as a contributor to atherosclerosis, and the potential role of antibiotic therapy in the treatment of atherosclerosis . Onkologie, 2003 Feb, 26(1), 73 - 9 Granulocyte transfusion therapy for treatment of infections after cytotoxic chemotherapy; Hubel K et al.; Opportunistic fungal infections and antibiotic-refractory bacterial infections remain important causes of morbidity and mortality in neutropenic individuals . Furthermore, the expanding use of dose-intensive cancer treatment strategies has increased the frequency of prolonged neutropenia . Therefore, the transfusion of granulocytes should be a logical therapeutic approach . Substantial progress has been made in the field of granulocyte transfusion therapy during the past decade . Interest in granulocyte transfusion therapy has been rekindled by both the use of hematopoietic growth factors to mobilize neutrophils and modern leukapheresis techniques . Moreover, promising results were observed in the use of community donors and in granulocyte storage experiments, which could enhance the ability of blood banks for institution of granulocyte concentrates . Recent clinical trials suggest that granulocyte transfusion therapy may be effective and well-tolerated in the neutropenic patient affected by life-threatening infections . These results must be confirmed in controlled, clinical trials . Int J Pediatr Otorhinolaryngol, 2003 Feb, 67(2), 177 - 9 Chlamydia infection in children with acquired subglottic stenosis; Soldatski IL et al.; The purpose of the study was to find out the frequency of occurrence and the role of Chlamydia infection in the pathogenesis of acquired subglottic stenosis in children . Forty-nine patients of the age from 1 year 10 months to 15 years with acquired cicatricial laryngotracheal stenosis were examined . The immunofluorescent method was used to detect serum antibodies to the antigens of Chlamydia trachomatis and Chlamydia pneumoniae . Dilutions of 1:32 for C . trachomatis and 1:64 for C . pneumoniae were considered positive . The results of the study suggested both a high frequency (26.5%) of Chlamydia infection (C . pneumoniae) of the children with acquired subglottic stenosis, as well as 92% of infected children were either with tracheotomies or had been decannulated earlier . It reasonable to test children with a tracheostomy for the presence of Chlamydia infection to perform timely and specific antibiotic therapy. J Can Dent Assoc . 2003 Mar;69(3):160. Emergency management of acute apical periodontitis in the permanent dentition: a systematic review of the literature; Sutherland S et al.; OBJECTIVE: To perform a systematic literature review and meta-analysis on the effectiveness of interventions used in the emergency management of acute apical periodontitis in the permanent dentition . METHODS: Electronic databases were searched from their inception to 2001 . These searches, combined with manual searching, yielded 1,097 citations, of which 92 were relevant . Independent application of inclusion criteria by 2 teams of reviewers yielded 15 eligible randomized controlled trials . Data on population, interventions, outcomes (pain relief or change in intensity of pain as reported by patients or clinicians) and methodological quality were determined by independent duplicate review . Disagreements were resolved by consensus . RESULTS: Meta-analysis showed that pre-emptive analgesics (nonsteroidal anti-inflammatory drugs {NSAIDs}) in conjunction with pulpectomy provided a significant benefit (weighted mean difference -11.70, 95% confidence interval -22.84 to -0.56) . Three interventions did not show significant benefit: systemic antibiotics, intracanal treatment with a steroid-antibiotic combination, and trephination through attached gingiva . CONCLUSIONS: In the management of pain associated with acute apical periodontitis, there is strong evidence to support the use of systemic NSAIDs in conjunction with nonsurgical endodontics . The use of antibiotics is not recommended. Urologiia, 2003 Jan-Feb, (1), 55 - 8 {Urogenital chlamydia infection: treatment with wilprafen}; Iakubovich AI et al.; Antibiotic wilprafen (josamycin) was given in a dose 500 mg per os two times a day for 15 days to 30 male patients with a long history of chronic Chlamydia trachomatis infection (CTI) treated ineffectively . The control examination has not detected Chlamydia in 29 (96.5%) patients . The results demonstrate high efficacy of the drug wilprafen in the treatment of patients with urogenital CTI. Wien Med Wochenschr, 2003, 153(1-2), 37 - 9 {Therapy of head injuries caused by animal slaughter guns}; Crevenna R et al.; Slaughterer's guns ("humane killers") are powder-activated cattle skull impacting tools . Today mechanical stunning is typical for country like regions, because in the municipal slaughter-houses electrical stunning of pigs and ruminants is preferred . In rare cases these weapons are used for suicide . They then cause penetrating brain lesions and if the victim survives the brain-damage, an encephalitis caused by the impacted material results . The neurosurgical treatment is to revise the gunshot canal and to remove impacted fragments of bone and contaminated skin (imprimat) under antibiotic cover . A psychiatric treatment of the mostly underlying depression and a rehabilitative treatment should complete therapy . So treatment of slaughterer's gun injury should have a multidisciplinary approach. Aesthetic Plast Surg, 2002 Nov-Dec, 26(6), 470 - 6 Improving scar quality: a prospective clinical study; Atiyeh BS et al.; Following traumatic or surgical injury to the skin, wounds do not heal by tissue regeneration but rather by scar formation . Though healing is definitely a welcomed event, the resultant scar, very often, is not aesthetically pleasing, and not infrequently, may be pathologic causing serious deformities and contractures . Management of problematic scars continues to be a frustrating endeavor with less than optimal results . Prophylactic methods of wound management to minimize serious scarring are being developed . In a previously published study, we have demonstrated improved healing of split thickness skin graft donor sites following treatment with Moist Exposed Burn Ointment (MEBO, Julphar Gulf Pharmaceutical Industries, Ras Al-Khaimah, UAE) . At present, we are reporting the results of a comparative clinical prospective study evaluating scar quality following primary healing of elective surgical and traumatic facial wounds with prophylactic MEBO application, topical antibiotic ointment application, and no topical therapy at all . Scars were evaluated according to the Visual Analogue Scale for scar assessment . Statistical analysis of scar assessment scores demonstrated marked prevention of unfavorable scars with improved cosmetic results following MEBO prophylactic therapy. Otol Neurotol, 2003 Mar, 24(2), 132 - 40 Mastoid obliteration: autogenous cranial bone pAte reconstruction; Roberson JB Jr et al.; OBJECTIVE: To review the outcome in consecutive patients who have undergone complete epitympanic and mastoid obliteration and concurrent tympanic membrane reconstruction over a 53-month period . STUDY DESIGN: Retrospective review . SETTING: Tertiary referral center . PATIENTS: Sixty-two ears in 56 sequential patients undergoing mastoid obliteration with major indications including recurrent infection, debris trapping in the canal wall-down cavity, intolerance of water exposure, calorically induced vertigo in an existing cavity, a semicircular canal fistula, and inability to wear a hearing device . Thirty-six ears in 33 patients who underwent second-stage surgery for ossicular reconstruction during the same time period are also reviewed . INTERVENTION: Transplanted autogenous cranial bone is used to induce osteoneogenesis resulting in complete obliteration of the epitympanic and mastoid spaces while maintaining a mesotympanic space . MAIN OUTCOME MEASURES: Success of obliteration, incidence of symptoms prompting intervention, hearing outcome, incidence of recurrent cholesteatoma, and incidence of eustachian tube dysfunction necessitating treatment and need for revision surgical procedures.RESULTS Complete take of the bony obliteration occurs in over 95% of cases; 90% of treated patients enjoy complete absence of original symptoms, whereas symptoms improved in the remainder . For over 95% of patients, existing eustachian tube function has been adequate after obliteration . To date, no patient has required revision surgical intervention . CONCLUSION: Mastoid obliteration with autogenous cranial bone is a safe and extremely effective option for treatment of problematic canal wall-down mastoid cavities . Surgical techniques that include sterile harvest of the cranial bone graft mixed with antibiotic, revision of the cavity to expose viable native bone, inclusion of the epitympanic spaces in the obliteration, and complete coverage of the pAte with autogenous fascia have proven critical to successful outcome. J Orthop Trauma, 2003 Mar, 17(3), 212 - 6 Gentamicin may have an adverse effect on osteogenesis; Isefuku S et al.; OBJECTIVE: To investigate the toxic effect of gentamicin at the high concentrations that can be achieved by local administration in the management of bone infection . DESIGN: Randomized, prospective study in cultured cells, with drug exposure duration of 4 days . SETTING: Cell culture in Dulbecco's modification of Eagle's minimal essential medium with supplements at 37 degrees C in air:CO2 (v:v, 95:5) . MATERIALS: Human osteoblastlike cells derived from cancellous bone collected from four adult patients without systemic disease during total hip replacement were cultured in antibiotic-free medium for 4 weeks . INTERVENTION: The cultured cells were exposed to media containing various concentrations of gentamicin (0-1000 microg/mL) for 4 days . MAIN OUTCOME MEASUREMENTS: Alkaline phosphatase activity, total DNA, and 3H-thymidine incorporation . RESULT: Alkaline phosphatase activity was significantly decreased (p < 0.05) in all of the cultures at gentamicin concentrations of 100 microg/mL and above . 3H-thymidine incorporation was also decreased (p < 0.05) in three out of four cultures at 100 microg/mL and above . Total DNA was significantly decreased (p < 0.05) at 700 microg/mL and above . CONCLUSION: Gentamicin, at high concentrations, as achieved following topical application, inhibits cell proliferation in vitro and, therefore, may be detrimental to the repair process in vivo. Plast Reconstr Surg, 2003 Mar, 111(3), 1309 - 18; discussion 1319-21 Nasal augmentation with Surgicel-wrapped diced cartilage: a review of 67 consecutive cases; Elahi MM et al.; Cartilage grafting has been used extensively to correct both the functional and aesthetic aspects of the nasal framework . The technique described by Erol ( 105: 2229, 2000) uses Surgicel-wrapped diced cartilage grafts in rhinoplasties . The advantages include its ease of preparation, the large volume of graft substrate available for use, and the avoidance of contour irregularities in the areas of placement . A retrospective case review of 67 consecutive patients who were treated with a Surgicel-wrapped diced cartilage graft as part of an aesthetic and/or functional rhinoplasty, in a 5-year period between 1995 and 2000, was performed in this study . All cases of congenital nasal deformities or deformities caused by trauma or tumors in which the technique was used were excluded . The charts were reviewed to determine demographic variables, the surgical procedures performed, prior operations, the rhinoplasty approach used, and the graft donor and recipient sites . Preoperative and postoperative photographs were examined, and the results were assessed . Data on the donor and recipient sites, complications, and the necessity for revisionary procedures were tabulated . There were two complications, namely, an infection, which resolved with aspiration and oral antibiotic therapy, and a recurrence of a dorsal depression, which necessitated repeated augmentation within 6 months . The technique of using Surgicel-wrapped diced cartilage proved to be effective for the augmentation of various areas of the nose . The complication and revision rates were acceptable and comparable to those of other techniques . Patient satisfaction with the aesthetic results was rated highly, with no reports of graft extrusion or contour irregularities . This technique is recommended for nasal augmentation and contouring for selected rhinoplasty patients. J Med Microbiol, 2003 Mar, 52(Pt 3), 193 - 200 Chlamydia trachomatis-induced death of human spermatozoa is caused primarily by lipopolysaccharide; Hosseinzadeh S et al.; Elementary bodies (EBs) of Chlamydia trachomatis serovar E are more toxic to sperm than those from serovar LGV . In this study, lipopolysaccharide (LPS) was prepared from the EBs of both serovars and incubated with human spermatozoa at concentrations that matched the LPS concentration of EBs . The effects of EBs and LPS on sperm motility, viability and acrosomal status were then determined . Sperm motility was measured by computer-assisted sperm analysis and the hypo-osmotic swelling test was used to determine the proportion of dead cells . Acrosomal status was examined using a standard mAb assay . Over a 6 h incubation, LPS from both serovars resulted in a marked reduction in sperm motility (and a concomitant increase in the proportion of dead spermatozoa) in a manner similar to that seen in response to EBs of serovar E . In addition, when sperm were incubated with a range of doses of EBs and LPS, probit analysis revealed that the greater spermicidal effects of EBs from serovar E (when compared with serovar LGV) were not observed when sperm were incubated with LPS from the two serovars . This suggests that the more potent effect of EBs of serovar E cannot be explained entirely by differences in the composition of LPS . Interestingly, Escherichia coli LPS was required in doses 500 times more concentrated than chlamydial LPS in order to kill a similar proportion of sperm, suggesting that bacterial LPSs may differ in their spermicidal properties . However, that chlamydial LPS was spermicidal was demonstrated by the use of polymyxin B (a polycationic antibiotic known to neutralize LPS effects), confirming that the effects observed were primarily a result of LPS activity. FEMS Microbiol Lett, 2003 Feb 28, 219(2), 285 - 9 Isolation and characterization of bluensomycin biosynthetic genes from Streptomyces bluensis; Jung YG et al.; The biosynthetic gene cluster for bluensomycin, a member of the aminoglycoside family of antibiotics, was isolated and characterized from the bluensomycin producing strain, Streptomyces bluensis ATCC27420 . PCR primers were designed specifically to amplify a segment of the dTDP-glucose synthase gene based on its conserved sequences among several actinomycete strains . By screening a cosmid library using amplified PCR fragments, a 30-kb DNA fragment was isolated . Sequence analysis identified 15 open reading frames (ORFs), eight of which had previously been identified by Piepersberg et al . But seven are novel to this study . We demonstrated that one of these ORFs, blmA, confers resistance against the antibiotic dihydrostreptomycin, and another, blmD, encodes a dTDP-glucose synthase . These findings suggest that the isolated gene cluster is very likely to be responsible for the biosynthesis of bluensomycin. Biosci Biotechnol Biochem, 2003 Jan, 67(1), 127 - 38 Characterization of the biosynthetic gene cluster of rebeccamycin from Lechevalieria aerocolonigenes ATCC 39243; Onaka H et al.; The biosynthetic gene cluster for rebeccamycin, an indolocarbazole antibiotic, from Lechevalieria aerocolonigenes ATCC 39243 has 11 ORFs . To clarify their functions, mutants with rebG, rebD, rebC, rebP, rebM, rebR, rebH, rebT, or orfD2 disrupted were constructed, and the gene products were examined . rebP disruptants produced 11,11'-dichlorochromopyrrolic acid, found to be a biosynthetic intermediate by a bioconversion experiment . Other genes encoded N-glycosyltransferase (rebG), monooxygenase (rebC), methyltransferase (rebM), a transcriptional activator (rebR), and halogenase (rebH) . rebT disruptants produced rebeccamycin as much as the wild strain, so rebT was probably not involved in rebeccamycin production . Biosynthetic genes of staurosporine, an another indolocarbazole antibiotic, were cloned from Streptomyces sp . TP-A0274 . staO, staD, and staP were similar to rebO, rebD, and rebP, respectively, all of which are responsible for indolocarbazole biosynthesis, But a rebC homolog, encoding a putative enzyme oxidizing the C-7 site of pyrrole rings, was not found in the staurosporine biosynthetic gene cluster . These results suggest that indolocarbazole is constructed by oxidative decarboxylation of chromopyrrolic acid (11,11'-dichlorochromopyrrolic acid in rebeccamycin) generated from two molecules of tryptophan by coupling and that the oxidation state at the C-7 position depends on the additional enzyme(s) encoded by the biosynthetic genes. Rev Neurol (Paris), 2003 Jan, 159(1), 77 - 9 {An atypical infectious paraplegia}; Sibon I et al.; Spinal cord abscess is an unusual cause of progressive paraplegia . We report the case of a 75-year-old man who presented Chlamydia pneumoniae bronchopulmonary infection with secondary spinal cord localization . Little clinical improvement was observed with antibiotic therapy, but the neuroradiological course was favorable. Chem Biol, 2003 Feb, 10(2), 175 - 87 Encapsulating streptomycin within a small 40-mer RNA; Tereshko V et al.; We describe a 2.9 A X-ray structure of a complex between the aminocyclitol antibiotic streptomycin and an in vitro selected RNA aptamer, solved using the anomalous diffraction properties of Ba cations . The RNA aptamer, which contains two asymmetric internal loops, adopts a distinct cation-stabilized fold involving a series of S-shaped backbone turns anchored by canonical and noncanonical pairs and triples . The streptomycin streptose ring is encapsulated by stacked arrays of bases from both loops at the elbow of the L-shaped RNA architecture . Specificity is defined by direct hydrogen bonds between all streptose functional groups and base edges that line the inner walls of the cylindrical binding pocket . By contrast, the majority of intermolecular interactions involve contacts to backbone phosphates in the published structure of streptomycin bound to the 16S rRNA. Chem Biol, 2003 Feb, 10(2), 161 - 8 EF-Tu binding peptides identified, dissected, and affinity optimized by phage display; Murase K et al.; The highly abundant GTP binding protein elongation factor Tu (EF-Tu) fulfills multiple roles in bacterial protein biosynthesis . Phage-displayed peptides with high affinity for EF-Tu were selected from a library of approximately 4.7 x 10(11) different peptides . The lack of sequence homology among the identified EF-Tu ligands demonstrates promiscuous peptide binding by EF-Tu . Homolog shotgun scanning of an EF-Tu ligand was used to dissect peptide molecular recognition by EF-Tu . All homolog shotgun scanning selectants bound to EF-Tu with higher affinity than the starting ligand . Thus, homolog shotgun scanning can simultaneously optimize binding affinity and rapidly provide detailed structure activity relationships for multiple side chains of a polypeptide ligand . The reported peptide ligands do not compete for binding to EF-Tu with various antibiotic EF-Tu inhibitors, and could identify an EF-Tu peptide binding site distinct from the antibiotic inhibitory sites. Chem Biol, 2003 Feb, 10(2), 103 - 4 Aptamer structures: a preview into regulatory pathways? Piganeau N, Schroeder R. The crystal structure of a streptomycin binding RNA aptamer displays a novel bipartite fold able to clamp the antibiotic . In view of the recent findings that metabolites directly control mRNA translation, we might expect that similar structures exist in natural RNAs. J Am Anim Hosp Assoc, 2003 Mar-Apr, 39(2), 151 - 9 Ultrasound-guided percutaneous drainage as the primary treatment for prostatic abscesses and cysts in dogs; Boland LE et al.; Thirteen dogs with prostatic abscesses and cysts were treated using percutaneous ultrasound-guided drainage . Eight dogs were diagnosed with prostatic abscesses and five with cysts on the basis of cytopathological examination and bacterial culture of the prostatic fluid . Antibiotic therapy, based on culture and sensitivity results, was administered for a minimum of 4 weeks . Intact dogs were castrated after initial drainage . Repeat ultrasonography of the prostate was performed every 1 to 6 weeks, and any residual cavitary lesions were drained and fluid analysis repeated . The median number of drainage procedures required to completely resolve the lesions was two (range, one to four) . No complications were observed after drainage, and clinical signs resolved in all dogs . None of the dogs developed clinical signs of recurrent abscesses or cysts in the follow-up period (median, 36 months; range, 10 to 50 months) . Ultrasound-guided, percutaneous drainage of prostatic abscesses and cysts appears to be a useful alternative to surgical treatment in select dogs. J Antibiot (Tokyo), 2002 Dec, 55(12), 1031 - 5 Parimycin: isolation and structure elucidation of a novel cytotoxic 2,3-dihydroquinizarin analogue of gamma-indomycinone from a marine streptomycete isolate; Maskey RP et al.; In our screening of actinomycetes from the marine environment for bioactive components, a new antibiotic with a novel structure designated as parimycin was obtained from the culture broth of Streptomyces sp . isolate B8652 . The structure of the new antibiotic was determined by spectroscopic methods and by comparison of the NMR data with those of the structurally related gamma-indomycinone. Ren Fail, 2003 Jan, 25(1), 115 - 21 Relationship between serum N-carbamoyl-beta-D-glucopyranosylamine level and renal failure; Hamafuji T et al.; A statistical investigation was carried out on the distribution of serum N-carbamoyl-beta-D-glucopyranosylamine (NCG) among various patient groups . The serum NCG levels of patients treated in the departments of hemodialysis (131 +/- microM), nephritic syndrome (47 +/- 54 microM), and diabetes mellitus (55 +/- 70 microM) were significantly higher (p < 0.01) than those in other internal disease patients (18 +/- 22 microM) and healthy volunteers (6 +/- 22 microM) . The serum NCG level was greatly reduced by hemodialysis therapy, however a return to initial NCG levels was observed within about one week . These results indicate that a high serum NCG level is a feature of renal failure patients, and a relationship was demonstrated between hyperuremia and NCG formation and accumulation in blood. World J Surg, 2003 Feb, 27(2), 130 - 3 Breast abscesses in lactating women; Dener C et al.; We designed a prospective study to assess the contributing factors in puerperal breast abscess and to evaluate the treatment options . During the 4-year study period, 128 nursing women with breast infection were followed . Of these, 102 had mastitis (80%) and 26 had breast abscess (20%) . Ultrasonographic examination was performed in all cases . Patient age, parity, localization of infection, cracked nipples, duration of lactation, duration of symptoms, milk culture results, breast infections during previous lactation period, treatment options, healing time, and recurrence were recorded prospectively . All mastitis patients were treated with antibiotics and none developed an abscess . Ten abscesses were aspirated, and 16 abscesses were treated by incision and drainage . Healing times were similar . There was no significant difference between mastitis and abscess groups regarding age, parity, localization of breast infection, cracked nipples, positive milk cultures, or mean lactation time . Duration of symptoms and healing were longer in cases of abscess . Multivariate analyses showed that duration of symptoms was the only independent variable for abscess development . Recurrent mastitis developed in 13 patients (10.2%) within a median of 24 weeks of follow-up . Delayed treatment of mastitis can lead to abscess formation, and it can be prevented by early antibiotic therapy . Ultrasonography is helpful for detecting abscess formation . In selected cases the abscess can be drained with needle aspiration with excellent cosmesis. Laryngoscope, 2003 Mar, 113(3), 557 - 62 Highlights in the evolution of diagnosis and treatment of laryngeal cancer; Assimakopoulos D et al.; OBJECTIVES: To present selected highlights from the evolution of diagnosis of laryngeal disease and treatment of laryngeal cancer from ancient Greece until the 20th century . STUDY DESIGN: Historical study of diagnosis of laryngeal disease and treatment of laryngeal cancer from the ancient Greek medical scriptures until the most recent evolutional steps in the 20th century . METHODS: Original Greek-language texts of ancient and Byzantine medical writers were studied and literature on history of medicine was investigated to reveal early knowledge of diagnostic and therapeutic techniques for laryngeal disease and cancer of the larynx . RESULTS: Diseases of the upper aerodigestive tract were known and treated by ancient Greek physicians, and, later, Byzantine doctors, apart from preserving ancient medical concepts, contributed their own ideas, mainly about surgery and postoperative care . The initial therapeutic approach for the disorders caused by laryngeal tumors was either tracheotomy or endotracheal intubation in an attempt to prevent suffocation . In more recent times, construction of the laryngoscope and other modern examination instruments, as well as the final acceptance of histological diagnosis based on tissue biopsy, has allowed for accurate diagnosis and successful treatment of laryngeal lesions . Preoperational biopsy, application of pharyngoesophageal speech and advanced vocal devices for the laryngectomees, and invention of antibiotic and anesthetic agents had led, by the middle of the 20th century, to the establishment of extended and radical surgical techniques as optional treatment for laryngeal cancer . In addition, the discovery of x-rays and radium introduced radiotherapy as an alternative in the treatment procedure for cancer of the larynx . CONCLUSION: Progress in the evolution of laryngological diagnosis and practice demanded efforts by many daring and courageous investigators and surgeons, contributing new ideas and techniques in the development of modern laryngology. Ann Surg, 2003 Mar, 237(3), 363 - 7 Colon and rectal surgery without mechanical bowel preparation: a randomized prospective trial; Zmora O et al.; OBJECTIVE: To assess whether elective colon and rectal surgery can be safely performed without preoperative mechanical bowel preparation . SUMMARY BACKGROUND DATA: Mechanical bowel preparation is routinely done before colon and rectal surgery, aimed at reducing the risk of postoperative infectious complications . However, in cases of penetrating colon trauma, primary colonic anastomosis has proven to be safe even though the bowel is not prepared . METHODS: Patients undergoing elective colon and rectal resections with primary anastomosis were prospectively randomized into two groups . Group A had mechanical bowel preparation with polyethylene glycol before surgery, and group B had their surgery without preoperative mechanical bowel preparation . Patients were followed up for 30 days for wound, anastomotic, and intra-abdominal infectious complications . RESULTS: Three hundred eighty patients were included in the study, 187 in group A and 193 in group B . Demographic characteristics, indications for surgery, and type of surgical procedure did not significantly differ between the two groups . Colo-colonic or colorectal anastomosis was performed in 63% of the patients in group A and 66% in group B . There was no difference in the rate of surgical infectious complications between the two groups . The overall infectious complications rate was 10.2% in group A and 8.8% in group B . Wound infection, anastomotic leak, and intra-abdominal abscess occurred in 6.4%, 3.7%, and 1.1% versus 5.7%, 2.1%, and 1%, respectively . CONCLUSIONS: These results suggest that elective colon and rectal surgery may be safely performed without mechanical preparation. J Chromatogr A, 2003 Feb 14, 987(1-2), 235 - 41 Determination of amoxycillin in human plasma by direct injection and coupled-column high-performance liquid chromatography; Cass QB et al.; This work reports the use of multidimensional HPLC by coupling a restricted access medium (RAM) bovine serum albumin (BSA) octadecyl column (100 x 4.6 mm I.D., 10 microm particle size and 120 A pore size) to an octadecyl Hypersil column (150 x 4.6 mm I.D., 5 microm particle size and 120 A pore size) to the analysis of amoxycillin in human plasma by direct injection . Ion pairing was necessary to extract amoxycillin with good recovery from the plasma proteins . To prepare the spiked samples, aliquots (60 microl) of the appropriated standard solutions were added to each culture tube containing an 180 microl of plasma and a solution of 0.30 mM tetrabuthylammonium phosphate (60 microl) . They were vortexed for 15 s and then 290 microl were transferred to autosampler vials . Aliquots (250 microl) of the spiked plasma samples were injected to a column-switching HPLC system . An analysis time of 25 min with no time spent on sample preparation was achieved . The developed method showed good selectivity, sensitivity, accuracy and precision for direct analysis of this polar low wavelength ultraviolet absorption antibiotic using only 180 microl of human plasma . The validated method proved to be reliable and sensitive for the determination of amoxycillin in plasma samples of five healthy volunteers to whom test and reference formulations were administered as an oral dose (500 mg). Chemistry, 2002 Nov 15, 8(22), 5228 - 40 Experimental evidence for the existence of non-exo-anomeric conformations in branched oligosaccharides: NMR analysis of the structure and dynamics of aminoglycosides of the neomycin family; Asensio JL et al.; It is commonly known that the exo-anomeric effect is a major factor governing the conformational behavior of naturally occurring oligosaccharides . Conformational flexibility in these molecules mainly concerns the aglycon psi angle since phi is restricted by this stereo-electronic effect . In fact, to the best of our knowledge no case of a natural glycoside adopting a non-exo-anomeric conformation in solution has yet been reported . With respect to the flexibility among naturally occurring carbohydrates, branched type oligosaccharides including sugar residues glycosidated at contiguous positions (such as blood type carbohydrate antigens Lewis X) have been considered as the paradigm of rigid saccharides--the rigidity being enhanced by van der Waals interactions . Herein, we demonstrate unambiguously that both common beliefs are not to be generalized . For example in neomycin B, a branched oligosaccharide antibiotic, a large number of non-exo-anomeric conformations was detected in solution for the first time in naturally occurring sugars . This unusual behavior is attributed to branching . Here, polar contacts between non-vicinal sugar units lead to an enhanced flexibility of the ribose glycosidic torsion phi . The influence of sugar flexibility on RNA recognition will also be discussed. Klin Monatsbl Augenheilkd, 2003 Jan-Feb, 220(1-2), 60 - 2 {VI: Confidence intervals--an alternative for p values}; Krummenauer F; Confidence intervals combine the ideas of clinical relevance and statistical significance by using one instructive expression, which enables remarkable reduction of table structures and result sections in scientific publications . Confidence interval based conclusions can be transferred from a clinical trial to its underlying study population with respect to a residual statistical error probability, i.e . the significance concept is retained . However, their presentation using the original unit of the clinical endpoint under consideration allows for immediate interpretation of the results' clinical impact . For example, the comparison of two therapy groups based on a binary endpoint becomes feasible using the relative risk's confidence interval . If "1" is not contained in the interval, the therapy groups significantly differ concerning this endpoint . The larger the interval turns out, the less precise the characterisation of the "real" risk value based on the study risk estimate . The larger the risk estimate turns out, the more clinical relevance. Curr Genet, 2003 Mar, 42(6), 344 - 52 Epub 2003 Feb 07. Transformation of Pythium aphanidermatum to geneticin resistance; Weiland JJ; Conditions for the production of protoplasts and gene transfer in Pythium aphanidermatum were investigated . Efficient protoplast generation was possible after culture of mycelium in potato dextrose broth followed by digestion with 0.5% (w/v) each of cellulase and beta- d-glucanase . Plasmid pHAMT35N/SK encoding the nptII gene under control of the Ham34 promoter from the oomycete Bremia lactucae was used to define electroporation parameters for gene transfer . A square-wave electroporation pulse of 2500 V/cm at 50 microF capacitance reproducibly produced transformants, albeit at low efficiency (0.1-0.4 transformants from approximately 10(5) regenerable protoplasts per microgram of DNA) . Thirty-two independent transformants exhibited wild-type growth on potato dextrose agar amended with geneticin at 50 microg/ml, a concentration that near completely inhibited the growth of untransformed P . aphanidermatum . Southern blot analysis indicated that transforming DNA was integrated into the oomycete genome and that the DNA was stably inherited through sporogenesis . Growth on geneticin-free media, the ability to form zoospores or oospores, and the ability to cause disease in sugarbeet seedlings in the laboratory were indistinguishable between a subset of the transformed isolates and the progenitor isolate 898B . Co-electroporation of pHAMT35N/SK with plasmid pACT-GUS encoding the Escherichia coli gusA gene controlled by oomycete transcriptional promoter and terminator sequences or with pEGFP encoding enhanced green fluorescent protein under the control of the immediate early promoter from the mammalian cytomegalovirus produced, respectively, stable beta-glucuronidase and transient expression of blue-green fluorescence . Application of the technique to studies on the biochemical basis for pathogenesis in this agriculturally important group of fungi is discussed. J Cell Mol Med, 2002 Oct-Dec, 6(4), 539 - 53 Activated c-Met signals through PI3K with dramatic effects on cytoskeletal functions in small cell lung cancer; Maulik G et al.; Small cell lung cancer (SCLC) is an aggressive illness with early metastases . There are several receptor tyrosine kinases (RTKs) overexpressed in SCLC, including c-Met . c-Met contains an external semaphorin-like domain, a cytoplasmic juxtamembrane domain, tyrosine kinase domain and multiple tyrosines that bind to adapter molecules . We have previously reported that c-Met is abundantly expressed in the NCI-H69 SCLC cell line and now have determined the downstream effects of stimulating c-Met via its ligand hepatocyte growth factor (HGF) . Utilizing unique phospho-specific antibodies generated against various tyrosines of c-Met, we show that Y1003 (binding site for c-Cbl and a negative regulatory site), Y1313 (binding site for PI3K), Y1230/Y1234/Y1235 (autophosphorylation site), Y1349 (binding site for Grb2), Y1365 (important in cell morphogenesis) are phosphorylated in response to HGF (40 ng/ml, 7.5 min) in H69 cells . Since multiple biological and biochemical effects are transduced through the PI3K pathway, we determine the role of PI3K in the c-Met/HGF stimulation pathway . We initially determined that by inhibiting PI3K with LY294002 (50 microM over 72 hours), there was at least a 55% decrease in viability of H69 cells . Since H69 SCLC cells form clusters in cell culture, we determined the effects of HGF and LY294002 on cell motility of the clusters by time-lapse video microscopy . In response to HGF, SCLC moved much faster and formed more clusters, and this was inhibited by LY294002 . Finally, we determined the downstream signal transduction of HGF stimulation of c-Met with and without inhibition of c-Met (with geldanamycin, an anisamycin antibiotic that inhibits c-Met in SCLC) or PI3K (with LY294002) . We show that association of c-Met with PI3K and GAB2 is diminished by inhibiting c-Met . In summary, activation of the c-Met pathway targets the PI3K pathway in SCLC and this may be an important therapeutic target. Arch Surg, 2003 Mar, 138(3), 314 - 24 Risk factors for postoperative infectious complications in noncolorectal abdominal surgery: a multivariate analysis based on a prospective multicenter study of 4718 patients; Pessaux P et al.; HYPOTHESIS: Infectious complications are the main causes of postoperative morbidity in abdominal surgery . Identification of risk factors, which could be avoided in the perioperative period, may reduce the rate of postoperative infectious complications . DESIGN: A database was established from 3 prospective, randomized, multicenter studies . Multivariate analysis was performed using nonconditional logistic regression expressed as an odds ratio (OR) . SETTING: Multicenter studies (ie, private medical centers, institutional hospitals, and university hospitals) . PATIENTS: From June 1982 to September 1996, a database was established containing the information of 4718 patients who underwent noncolorectal abdominal surgery . MAIN OUTCOME MEASURES: The dependent variables studied included surgical site infection (SSI) (divided into parietal and deep infectious complications with or without fistulas) and global infectious complications (SSI and extraparietal and abdominal infectious complications) . RESULTS: The rate of global infectious complications was 13.3%; SSI, 4.05%; parietal infectious complications, 2.2%; deep infectious complications with fistulas, 2.18%; and deep infectious complications without fistulas, 1.38% . In multivariate analysis, the following 7 independent risk factors for global infectious complications have been identified: age (60-74 years, OR, 1.64; >or=75 years, OR, 1.45); being underweight (OR, 1.51); having cirrhosis (OR, 2.45), having a vertical abdominal incision (OR, 1.66); having a suture placed or an anastomis of the bowel (OR, 1.48) in the digestive tract; having a prolonged operative time (61-120 minutes, OR, 1.66; 121 minutes, OR, 2.72); and being categorized as having a class 4 surgical site (ie, obese patients or having a risk factor of a healing defect) (OR, 1.66) . Ceftriaxone sodium therapy was identified as a protective factor (OR, 0.43) . In multivariate analysis, the following 5 independent risk factors for SSI have been identified: the existence of a preoperative cutaneous abscess or cutaneous necrosis (OR, 4.75), having a suture placed or an anastomosis of the bowel (OR, 1.82) in the digestive tract, having postoperative abdominal drainage (OR, 2.15), undergoing a surgical procedure for the treatment of cancer (OR, 1.74), and receiving curative anticoagulant therapy (OR, 3.33) postoperatively . CONCLUSIONS: Our data show that risk factors for SSI and for global infectious complications are disparate . Indeed, only the placement of a suture or having an anastomosis of the bowel in the digestive tract is a risk factor for both SSI and global infections . Some of these factors may be modifiable before or during the surgical procedure to reduce the infection rate or to prevent postoperative complications. Inorg Chem, 2003 Mar 10, 42(5), 1420 - 9 Solution chemistry of copper(II)-gentamicin complexes: relevance to metal-related aminoglycoside toxicity; Lesniak W et al.; The adverse effect to the inner ear of aminoglycosides, drugs widely administered for the treatment of serious infections, appears to result from the interaction of these drugs with Cu(II) or Fe(II)/Fe(III) ions . To understand more completely the metal-induced side effects of one such antibiotic, gentamicin, we studied copper(II) coordination to gentamicin C1a by potentiometry, UV-vis, CD, and EPR spectroscopies, and ESI mass spectrometry . Only monomeric complexes of the CuH(n)L stoichiometry, with n ranging from 3 to -2, were detected over the pH range of 4-12 . CuH(3)L and CuH(2)L complexes exhibit the same coordination mode, binding copper(II) through the amino nitrogen atom and a deprotonated alcoholic oxygen atom of the garosamine ring . In the CuHL and CuL complexes a second amino nitrogen atom of the purpurosamine ring participates in central ion coordination . Finally, the additional axial binding of the deprotonated oxygen of the hydroxyl group of the 2-deoxystreptamine moiety occurs in the CuH(-)(1)L and CuH(-)(2)L complexes . Interactions of the Cu(II)-gentamicin-H(2)O(2) system at pH 7.4 with N,N-dimethyl-p-nitrosoaniline, arachidonic acid, and plasmid DNA confirmed that gentamicin complexes facilitate oxidative reactions leading to peroxidation of arachidonic acid and scission of double-stranded DNA mediated by copper-bound reactive oxygen species . However, the stability constants of Cu(II)-gentamicin complexes are inferior to the binding constants of copper(II) complexes with other components of human serum or cells . Computer simulations of copper(II) distribution in the human blood plasma showed that the concentration of gentamicin would have to be at impossible levels (100 M) before a significant fraction of Cu(II) ions would be bound to gentamicin . Further, once introduced into aqueous solution, histidine replaces gentamicin in Cu(II)-gentamicin complexes . Therefore, Cu(II)-gentamicin complexes might not exist under physiological conditions. Plant Cell Physiol, 2003 Feb, 44(2), 183 - 9 Inhibition of plastid division by ampicillin in the pteridophyte Selaginella nipponica Fr . et Sav; Izumi Y et al.; We investigated the effect of the beta-lactam antibiotic, ampicillin, on plastid division in the pteridophyte Selaginella nipponica . Guard cells of plantlets treated with 1 mM ampicillin only often had one plastid, whereas guard cells of untreated plantlets had two to four plastids . We generated a S . nipponica cell culture system and used it to investigate the effects of ampicillin . Treatment with 1 mM ampicillin had no effect on cell division in culture