Antibiotics

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 . We classified cultured cells into four types based on the number of plastids they contained: one (Type I), two (Type II), three or four (Type III) and more than five (Type IV) . After 3 d in culture, the percentage of each cell type (I-IV) was 29.5, 46.7, 20.9, and 1.9%, respectively . Subsequently, the percentage of Types III and IV increased gradually, reaching 61.9 and 11.4%, respectively, after 15 d in culture in the absence of ampicillin . When 1 mM ampicillin was added, there was a minimal increase in the number of Type III and IV cells, with high percentages of Type I and II cells (32.4 and 45.7%, respectively) after 15 d . These results suggest that ampicillin inhibits plastid division in S . nipponica.

J Org Chem, 2003 Mar 7, 68(5), 2038 - 41
A practical route to 3'-amino-3'-deoxyadenosine derivatives and puromycin analogues; Nguyen-Trung NQ et al.; 3'-aminoacylamino-3'-deoxyadenosines, analogues of the antibiotic puromycin, have been synthesized from adenosine . They key 3'-azido derivative 10 was obtained through a 3'-oxidation/reduction/substitution procedure . A modified purification protocol on a larger scale was developed for the oxidation step using the Garegg reagent . The coupling reaction between an Fmoc-l-amino acid and the fully protected form of 3'-amino-3'-deoxyadenosine 11 furnished the aminoacylated compounds 12 in high yields . The puromycin analogues were obtained in 10 steps and up to 23% (14c) overall yield.

J AOAC Int, 2003 Jan-Feb, 86(1), 22 - 9
Stability of florfenicol in drinking water; Hayes JM et al.; Florfenicol, a broad-spectrum antibiotic, is being developed for veterinary application as an oral concentrate intended for dilution with drinking water . When a drug product is dosed via drinking water in a farm setting, a number of variables, including pH, chlorine content, hardness of the water used for dilution, and container material, may affect its stability, leading to a decrease in drug potency . The stability of florfenicol after dilution of Florfenicol Drinking Water Concentrate Oral Solution, 23 mg/mL, with drinking water was studied . A stability-indicating, validated liquid chromatographic method was used to evaluate florfenicol stability at 25 degrees C at 5, 10, and 24 h after dilution . The results indicate that florfenicol is stable under a range of simulated field conditions, including various pipe materials and conditions of hard or soft and chlorinated or nonchlorinated water at low or high pH . Significant degradation (> 10%) was observed only for isolated combinations in galvanized pipes . Analysis indicated that the florfenicol concentration in 8 of the 12 water samples stored in galvanized pipes remained above 90% of the initial concentration (100 mg/L) for 24 h after dilution.

Ann Thorac Surg, 2003 Feb, 75(2), 342 - 7
Infectious necrotizing esophagitis: outcome after medical and surgical intervention; Gaissert HA et al.; BACKGROUND: Immunodeficiency predisposes to invasive esophageal infections . The treatment of perforation, respiratory fistula, and necrosis due to transmural esophageal infection is guided by anecdote . We wish to determine treatment and outcome of local complications of necrotizing esophagitis . METHODS: We report our experience over a 7-year period and review published reports since 1976 . We treated 4 patients and found 21 reported patients with perforation (11/25), fistula (8/25), and necrosis (6/25) at a mean age of 35 years . Twenty-one patients were immunodeficient (84%) due to acquired immunodeficiency syndrome in 8, acute leukemia in 6, renal transplant in 3, diabetes mellitus, renal failure, and corticosteroids in 1 each . Pathogenic organisms were fungal in 15 cases, viral in 7, and bacterial in 7 . RESULTS: Treatment consisted of antibiotic therapy in 13 patients and surgical intervention combined with antibiotic therapy in 12: esophagectomy in 6, esophageal stenting and drainage in 2, drainage alone in 2, and salivary diversion in 2 . Overall mortality was 48% (12/25) . Mortality without surgical intervention was 90% (9/10) and with surgical intervention 27% (3/11) . One of 6 patients undergoing esophagectomy (17%) died . The difference in mortality was due to sepsis, which was the cause of death in 8 patients treated with medical intervention and only 1 treated with surgical intervention . CONCLUSIONS: Local complications of necrotizing esophagitis have a high mortality due to sepsis . Surgical intervention, in particular esophagectomy, controls sepsis in published case reports and should be considered in selected patients . Further study is required to determine the true prevalence of these complications and the outcome of intervention.

Acta Paediatr Taiwan, 2002 Sep-Oct, 43(5), 271 - 5
Clinical spectrum of bronchiectasis in children; Tsao PC et al.; The prevalence of bronchiectasis decreased due to the effective use of vaccines and advances of antibiotic therapy after 1970 . However, it remains an important long-term morbidity of lower respiratory tract infection in developing country . To evaluate the clinical features of bronchiectasis in a tertiary hospital, we collected 21 patients with a diagnosis of bronchiectasis in Taipei Veterans General Hospital from May, 1984 to Dec, 2001 in pediatric outpatient with the admission of age below 18 years old . The diagnosis was based on the history of recurrent cough with fetid sputum, hemoptysis, or recurrent lobar pneumonia for months at least and radiological findings of lobar infiltration, tram-track like patterns, bronchiolar dilatation or honeycomb patterns . The diagnostic examinations included chest plain radiography, bronchography and chest computed tomography (CT) scans . Respiratory tract infections were the commonest cause predisposing to bronchiectasis in our study . Tuberculosis is not rare in this study . In recent years, immunodeficiency disorders have been recognized . Most patients suffered from recurrent cough and fetid sputum for years before diagnosis was established . Hemoptysis was the second common symptom in our study . The plain chest radiograph of bronchiectasis revealed dilatation of bronchial trees with honeycomb pattern or infiltration only . In recent years, chest CT became the most accurate and being noninvasive diagnostic tool . The initial treatment was primarily medical conservative therapy . Only five patients in our cases underwent pulmonary resection due to persistent hemoptysis, recurrent bacterial pneumonia or pulmonary parenchyma destruction . Most patients still suffered from recurrent pneumonia or occasional exacerbation in the long-term follow-up . In conclusion, bronchiectasis is not uncommon in pediatric population in northern Taiwan . The history of recurrent cough with fetid sputum, hemoptysis, or recurrent pneumonia were the most important clues to early diagnosis of this disease . Early diagnosis and appropriate treatment are effective in order to prevent lung abscess, empyema and pneumothorax, bronchopleural fistula, hemoptysis or cor pulmonale.

Org Lett, 2003 Mar 6, 5(5), 765 - 8
Synthesis of (+/-)-phloeodictine A1; Neubert BJ et al.; The antitumor antibiotic phloeodictine A1 (2) has been synthesized by a convergent seven-step route in 8% overall yield . The key step was the Eguchi aza-Wittig reaction of 6 to give 13 followed by a retro Diels-Alder reaction to liberate 5 . Addition of 11-dodecenylmagnesium bromide to 5 to give 4b, alkylation with 18b, and deprotection completed the first synthesis of 2.

J Exp Biol, 2003 Apr, 206(Pt 7), 1233 - 40
The toxic and lethal effects of the trehalase inhibitor trehazolin in locusts are caused by hypoglycaemia; Wegener G et al.; The main blood sugar of locusts is trehalose, which is hydrolysed to two glucose units by trehalase . Homogenates of locust flight muscles are rich in trehalase activity, which is bound to membranes . A minor fraction of trehalase is in an overt form while the remainder is latent, i.e . active only after impairing membrane integrity . Trehazolin, an antibiotic pseudosaccharide, inhibits locust flight muscle trehalase with apparent K(i)- and EC(50) values of 10(-8) mol l(-1) and 10(-7) mol l(-1), respectively . Trehazolin is insecticidal: 50 micro g injected into locusts completely and selectively blocked the overt form of muscle trehalase (with little effect on latent activity) and killed 50% of the insects within 24 h . Here, it is demonstrated for the first time that trehazolin causes dramatic hypoglycaemia . Injection of 10 micro g trehazolin caused glucose levels to fall by over 90% in 24 h, from 2.8 mmol l(-1) to 0.23 mmol l(-1), while trehalose increased from 61 mmol l(-1) to 111 mmol l(-1) . Feeding glucose to the locusts fully neutralized the effects of a potentially lethal dose of trehazolin . This indicates that hypertrehalosaemia is not acutely toxic, whereas lack of glucose causes organ failure (presumably of the nervous system), and that sufficient haemolymph glucose can only be generated from trehalose by trehalase . The results also suggest that overt flight muscle trehalase is located in the plasma membrane with the active site accessible to the haemolymph . Trehalase inhibitors are valuable tools for studying the molecular physiology of trehalase function and sugar metabolism in insects.

Antimicrob Agents Chemother, 2003 Mar, 47(3), 869 - 77
Resistance genes of aminocoumarin producers: two type II topoisomerase genes confer resistance against coumermycin A1 and clorobiocin; Schmutz E et al.; The aminocoumarin resistance genes of the biosynthetic gene clusters of novobiocin, coumermycin A(1), and clorobiocin were investigated . All three clusters contained a gyrB(R) resistance gene, coding for a gyrase B subunit . Unexpectedly, the clorobiocin and the coumermycin A(1) clusters were found to contain an additional, similar gene, named parY(R) . Its predicted gene product showed sequence similarity with the B subunit of type II topoisomerases . Expression of gyrB(R) and likewise of parY(R) in Streptomyces lividans TK24 resulted in resistance against novobiocin and coumermycin A(1), suggesting that both gene products are able to function as aminocoumarin-resistant B subunits of gyrase . Southern hybridization experiments showed that the genome of all three antibiotic producers and of Streptomyces coelicolor contained two additional genes which hybridized with either gyrB(R) or parY(R) and which may code for aminocoumarin-sensitive GyrB and ParY proteins . Two putative transporter genes, novA and couR5, were found in the novobiocin and the coumermycin A(1) cluster, respectively . Expression of these genes in S . lividans TK24 resulted in moderate levels of resistance against novobiocin and coumermycin A(1), suggesting that these genes may be involved in antibiotic transport.

Acta Pol Pharm, 2002 Sep-Oct, 59(5), 327 - 31
A simple and rapid liquid chromatographic method for the determination of metronidazole and its hydroxymetabolite in plasma and cutaneous microdialysates; Klimowicz A et al.; A rapid, accurate, simple and low-cost method for quantitative determination of metronidazole and its hydroxymetabolite, in plasma and microdialysate samples, using tinidazole as an internal standard, has been developed . Metronidazole is widely used as a valuable agent for antiprotozoal as well as antibiotic therapy when anaerobic organisms are involved . Separation of the compounds studied was performed on a 120 x 4 mm analytical column, filled with LiChrosorb RP-8, 5 microm, the mobile phase consisted of 0.05 mol/L aqueous solution of potassium dihydrogen phosphate, adjusted to pH = 3.5 with orthophosphoric acid, methanol and acetonitrile (40:2:3 . v/v/v) . Detection was performed at 320 nm . Intra- and interserial precision was below 4.6% and 7.9%, respectively, for both the compounds studied . The presented method is suitable for pharmacokinetic studies.

Prescrire Int, 2003 Feb, 12(63), 26 - 7
Fluoroquinolones in ambulatory ENT and respiratory tract infections: rarely appropriate; Bullous pyoderma gangrenosum complicated by disseminated intravascular coagulation with subsequent myelodysplastic syndrome (chronic myelomonocytic leukemia); Universitatsklinikum Leipzig AoR, Klinik und Poliklinik fur Hautkrankheiten, Leipzig, GermanyA 33-year-old woman developed a bullous PG precursing a chronic myelomonocytic leukemia (CMML) complicated by life-threatening, disseminated, intravascular coagulation after administration of systemic corticosteroids in combination with immunosuppressant and antibiotic agents . Although the association between PG and leukemia, as well as the coincidence of disseminated intravascular coagulation (DIC) and leukemia, is well known, a premonitoring effect of PG in combination with DIC preceding the diagnosis of chronic myelomonocytic leukemia in the same patient has not been reported recently.

Arch Dis Child, 2003 Mar, 88(3), 270 - 2
Mycoplasma pneumoniae associated organising pneumonia in a 10 year old boy; Wachowski O et al.; We describe a 10 year old boy with organising pneumonia associated with acute Mycoplasma pneumoniae infection . The diagnosis of organising pneumonia was made by open lung biopsy and the M pneumoniae infection was proven serologically . Antibiotic and long term corticosteroid treatment resulted in steadily improving pulmonary function monitored by spirometry . The introduction of anti-inflammatory treatment with NSAIDs/immunosuppressive agents in order to spare steroids was well tolerated and resulted in further improvement of the pulmonary function . To our knowledge this is the first documented case of Mycoplasma pneumoniae associated organising pneumonia to be reported in a child.

Crit Care Nurs Clin North Am, 2003 Mar, 15(1), 1 - 11
The cellular basis of bacterial infection; Workman ML; Innate and adaptive immune responses are responsible for the prevention of and recovery from bacterial infections . Fully immunocompetent humans make adaptations to the pathogens within their environment . Bacterial pathogens are capable of responding to immune adaptations to avoid destruction and elimination . Examination of the bacterial mechanisms of evasion has revealed the evolution of many elegant systems capable of thwarting host defenses . Undoubtedly, more mechanisms have yet to be discovered . A major concern as bacteria become more antibiotic resistant is whether human immune adaptation can evolve sufficiently to keep pace with bacterial evolution of evasion mechanisms.

J Pediatr Surg, 2003 Feb, 38(2), 236 - 42
Appendicitis in children: a ten-year update of therapeutic recommendations; Emil S et al.; BACKGROUND/PURPOSE: In 1990, the authors reported excellent outcomes using a standard protocol to treat pediatric appendicitis . This protocol has been simplified further and a large retrospective review was conducted to assess current outcomes . METHODS: All patients treated for presumed appendicitis between April 1997 and December 1999 were reviewed . All patients received preoperative gentamicin and clindamycin . Patients with complicated appendicitis received postoperative ampicillin, gentamicin, and clindamycin or metronidazole . All wounds were closed primarily without drains . Patients with complicated appendicitis were discharged when their ileus resolved, they remained afebrile for 24 hours, and had a normal leukocyte count . RESULTS: A total of 648 patients were reviewed . A total of 9.4% of appendices were pathologically normal, 55.6% were simple acute, 15.7% were gangrenous, and 19.3% were perforated . Hospital stay was 2.21 +/- 2.04 days for normal, 1.39 +/-.89 for simple acute, 2.97 +/- 1.25 for gangrenous, and 6.31 +/- 3.51 days for perforated appendices . There were no wound infections in patients with normal or simple acute appendices . Two minor intraabdominal infections (0.56%) occurred in patients with simple appendicitis . Patients with complicated appendicitis (gangrenous or perforated) had wound infection and intraabdominal infection rates of 2.6% and 4.4%, respectively . CONCLUSIONS: The authors' current protocol results in reasonable hospital stays and good outcomes . It serves as an evidence-based standard of care for the treatment of pediatric appendicitis .

Nucleic Acids Res, 2003 Mar 1, 31(5), 1464 - 9
The crystal structure of the complex between a disaccharide anthracycline and the DNA hexamer d(CGATCG) reveals two different binding sites involving two DNA duplexes; Temperini C et al.; The crystal structure of the complex formed between the anthracycline antibiotic 3'-deamino-3'- hydroxy-4'-(O-L-daunosaminyl)-4-demethoxydoxo rubicin (MEN 10755), an active disaccharide analogue of doxorubicin, and the DNA hexamer d(CGATCG) has been solved to a resolution of 2.1 A . MEN 10755 exhibits a broad spectrum of antitumor activities, comparable with that of the parent compound, but there are differences in the mechanism of action as it is active in doxorubicin-resistant tumors and is more effective in stimulating topoisomerase DNA cleavage . The structure is similar to previously crystallised anthracycline- DNA complexes . However, two different binding sites arise from drug intercalation so that the two halves of the self-complementary duplex are no longer equivalent . In one site both sugar rings lie in the minor groove . In the other site the second sugar protrudes out from the DNA helix and is linked, through hydrogen bonds, to guanine of a symmetry-related DNA molecule . This is the first structure of an anthracycline-DNA complex where an interaction of the drug with a second DNA helix is observed . We discuss the present findings with respect to the relevance of the amino group for DNA binding and to the potential role played by the second sugar in the interactions with topoisomerases or other cellular targets.

Biochimie, 2002 Nov, 84(11), 1119 - 26
Techniques for the removal of marker genes from transgenic plants; Scutt CP et al.; The presence of marker genes encoding antibiotic or herbicide resistances in genetically modified plants poses a number of problems . Various techniques are under development for the removal of unwanted marker genes, while leaving required transgenes in place . The aim of this brief review is to describe the principal methods used for marker gene removal, concentrating on the most recent and promising innovations in this technology.

J Am Coll Surg, 2003 Feb, 196(2), 212 - 21
Current practice patterns in the treatment of perforated appendicitis in children; Chen C et al.; BACKGROUND: The treatment of perforated appendicitis in children often involves a combination of surgical and medical therapy . The aim of this study was to document the degree of consensus in the current management of perforated appendicitis in children . STUDY DESIGN: A survey was sent to all practicing pediatric surgeons in North America in April 2000 who were members of the American Pediatric Surgical Association for 1999-2000 . Survey questions pertained to preoperative, perioperative, and postoperative practice patterns, particularly those issues related to use of antibiotic therapy . RESULTS: Among eligible surgeons, 80.2% completed the survey . Although more than 80% of respondents practiced in an academic setting, only 17% of surgeons used a formal clinical practice guideline to direct care . Responses varied substantially in the duration of postoperative antibiotic therapy, the use of intravenous or oral agents or both, and the duration of hospitalization . A considerable number of patients are receiving a portion of their intravenous antibiotic therapy as outpatients . CONCLUSIONS: There is little apparent consensus in the many aspects of perioperative and postoperative care of perforated appendicitis in children across North America . Only a fraction of surgeons currently uses a formal clinical practice guideline for treatment of perforated appendicitis, although increased pressures to develop more cost-effective therapeutic strategies can encourage development of additional guidelines . Definitive evidence to inform development of such guidelines and enhance consensus is lacking . Further studies are needed across institutions to better inform clinical decisions in light of a changing practice environment and treatment alternatives.

Surg Infect (Larchmt), 2002 Spring, 3(1), 5 - 9
A pilot study to determine the feasibility of continuous cefazolin infusion; Waltrip T et al.; BACKGROUND: Animal studies have shown that continuous infusion of beta-lactam antibiotics is more effective than intermittent dosing . We studied several dosing regimens of cefazolin in humans to determine safety and whether or not adequate serum and tissue antibiotic concentrations could be achieved in patients undergoing cardiac bypass . METHODS: A prospective, randomized pilot study was conducted at a university-affiliated teaching hospital over a 2-year period in patients undergoing first-time coronary artery bypass grafting . One hundred and thirty-seven patients were randomized to one of three groups . Group 1 (n = 64) received 1 g of cefazolin intravenously before operation and 1 g intravenously at the end of cardiopulmonary bypass . Group 2 (n = 35) received 2 g of cefazolin intravenously before operation, followed by a continuous intravenous infusion of cefazolin at 20 mg/min throughout surgery . Group 3 (n = 38) received 3 g of cefazolin intravenously before operation, followed by a continuous intravenous infusion of cefazolin at 15 mg/min throughout surgery . Venous blood and subcutaneous fat samples were obtained from the sternal wound in a subset of 34 patients at incision, 0.25 h, 0.5 h, and 1 h; at the end of cardiopulmonary bypass; and at wound closure . Venous blood was sampled in the recovery room and on postoperative day 1 . Cefazolin concentrations in the samples were determined by reverse-phase high-performance liquid chromatography using a C18 column . RESULTS: Serum cefazolin concentrations were higher for group 3 when compared with group 1 at all six intraoperative intervals (p < 0.02) and for group 2 when compared with group 1 at four of six intraoperative intervals (p < 0.04) . When compared with group 1, tissue cefazolin concentrations were higher for group 3 at all intraoperative intervals (p < 0.02) . No related toxicity or adverse events were observed . CONCLUSION: Cefazolin administered as a large preoperative bolus with continuous intraoperative infusion resulted in higher serum and tissue concentrations when compared with conventional intermittent dosing . Pharmacodynamically, continuous infusion of beta-lactam antibiotics may be superior to intermittent dosing when used for perioperative prophylaxis against wound infection, especially for cases in which the antibiotic is not redosed intraoperatively.

J Pediatr Surg, 2003 Jan, 38(1), 51 - 2
New technique for fixation of Broviac catheters; Sri Paran T et al.; Broviac catheters are in common use for administration of parenteral nutrition, cancer chemotherapy, and antibiotic therapy within the paediatric population . Inadvertent dislodgement of these catheters is common during the initial weeks before the Dacron cuff is anchored by the ingrowth of fibrous tissue . The authors describe a technique in which an internal fixation suture is placed to prevent dislodgement or migration .

Heart, 2003 Mar, 89(3), 269 - 72
Prosthetic valve endocarditis: early and late outcome following medical or surgical treatment; Akowuah EF et al.; OBJECTIVE: To compare the early and late outcome of medical and surgical treatment in patients with prosthetic valve endocarditis within a single unit . DESIGN: All patients with proven prosthetic valve endocarditis treated in one institution between 1989 and 1999 were studied . RESULTS: There were 66 patients (24 female, 42 male), mean (SD) age 57 (14) years . Of these, 28 were treated with antibiotics alone and 38 with a combination of antibiotics and surgery . The in-hospital mortality for the antibiotic group was 46% and for the surgical group, 24% . However, seven patients in the antibiotic group were considered too sick for curative treatment . The mortality in the remaining 21 medically treated patients (6/21; 29%) was not significantly different from that in the surgically treated patients (p = 0.15) . Six patients in the medically treated group and one in the surgically treated group required late reoperation . Endocarditis recurred in three patients in the medically treated group, two of whom were treated surgically, and in one patient in the surgically treated group . Kaplan-Meier survival at 10 years was 28% in the medically treated group v 58% in the surgically treated group (p = 0.04) . Freedom from endocarditis at five years was 60% in the surgically treated group and 65% in the medically treated group . CONCLUSIONS: Prosthetic valve endocarditis is a serious condition with high early and late mortality, irrespective of the treatment employed . These data show that selected patients with prosthetic valve endocarditis can be successfully treated with antibiotics alone . If required, surgery in this difficult group of patients can provide satisfactory freedom from recurrent infection.

Biochemistry, 2003 Feb 25, 42(7), 2166 - 73
Stimulation of DNA strand slippage synthesis by a bulge binding synthetic agent; Kappen LS et al.; It has been postulated that bulged structures may be intermediates in the DNA strand slippage synthesis associated with the expansion of nucleotide repeats in various neurodegenerative diseases and cancer . To probe the possible role of bulged structures in this process, we have synthesized a wedge-shaped spirocyclic molecule, DDI (double-decker intercalator), on the basis of our earlier work with the bulge-specific derivative prepared from the enediyne antitumor antibiotic neocarzinostatin chromophore . Using a series of primers/templates containing nucleotide repeats {(AAT)(3)/(ATT)(5), (ATT)(3)/(AAT)(5), (CAG)(3)/(CTG)(5), (CA)(4)C/(GT)(7)G, (GT)(4)G/(CA)(7)C, T(9)/A(30), T(20)/A(30)} with the Klenow fragment of Escherichia coli DNA polymerase I, we find that DDI markedly enhances the formation of long DNA products, whose synthesis would require strand slippage to occur . DDI-induced slippage synthesis is more pronounced as the incubation proceeds and at limiting enzyme levels . The gel band pattern of the synthesized DNA products reflects the particular nucleotide repeat unit and is not altered by DDI . The lack of any drug effect on primer extension on M13 DNA and heteropolymeric 62-mer templates, where strand slippage is much less likely to occur, suggests that stimulation of slippage synthesis by DDI is not due to a direct effect on the enzyme . By contrast, other DNA-binding agents, such as ethidium bromide, distamycin, and doxorubicin, inhibit the formation of slippage-induced DNA products, but this block can be overcome by DDI, presumably by its destabilizing duplex DNA-binding sites for these other agents . We propose that DDI binds to or induces the formation of a bulge or related structure, which promotes DNA strand slippage and its consequent expansion of nucleotide repeats during replication by DNA polymerase I and that this action provides insight into the development of agents that interfere with nucleotide expansions found in various disease states.

Mol Biol Cell, 2003 Feb, 14(2), 764 - 73
Geldanamycin treatment ameliorates the response to LPS in murine macrophages by decreasing CD14 surface expression; Vega VL et al.; Geldanamycin (GA) is an antibiotic produced by Actinomyces, which specifically inhibits the function of the heat shock protein 90 family . Treatment of a murine macrophage cell line (J774) with GA resulted in a reduced response to Escherichia coli lipopolysaccharide (LPS) as visualized by a decrease of NF-kappaB translocation into the nucleus and secretion of tumor necrosis factor alpha (TNF-alpha) . To elucidate the mechanism of this effect, the expression of CD14, the formal LPS receptor, was analyzed . Cells treated with GA showed a reduced level of surface CD14 detected by immunostaining, whereas the expression of other surface receptors, such as FC-gamma receptor and tumor necrosis factor receptors (TNF-R1 and TNF-R2), was unaffected . The reduced surface level of CD14 was not due to a reduction in its expression because CD14 steady state mRNA levels or the total cellular pool of CD14 was not altered by GA treatment . Surface CD14 was more rapidly internalized after GA treatment (2-3 h) than after incubation with cycloheximide . Immunostaining of permeabilized cells after GA treatment revealed a higher intracellular content of CD14 colocalizing with calnexin, an endoplasmic reticulum (ER) protein . These results suggest that the decrease in CD14 surface expression after GA treatment is due to rapid internalization without new replacement . These effects may be due to the inhibition of Hsp90 and Grp94 by GA in macrophages.

Chem Res Toxicol, 2003 Feb, 16(2), 171 - 9
Molecular characterization of mitomycin C-induced large deletions and tandem-base substitutions in the bone marrow of gpt delta transgenic mice; Takeiri A et al.; Deletion mutations constitute an important class of mutations that may result in a variety of human diseases, including cancer . Although many chemicals and ionizing radiations induce deletions, this class of mutation has been poorly characterized at the molecular level, particularly in vivo . Here we report the molecular nature of deletions as well as base substitutions induced by antitumor antibiotic mitomycin C (MMC) in the bone marrow using a novel transgenic mouse, gpt delta . In this mouse model, deletions and point mutations in lambda DNA integrated in the chromosome are individually selected as Spi(-) (sensitive to P2 interference) phages and 6-thioguanine-resistant bacterial colonies, respectively . The mice were treated with MMC (1 mg/kg/day) for five consecutive days . One week after the last treatment, lambda phage was rescued from the genomic DNA of the bone marrow by in vitro packaging reactions and subjected to Spi(-) and 6-thioguanine selections . The mutant frequency of Spi(-) with large deletions increased more than 20-fold over that of the control . Molecular sizes of the large deletions were mostly more than 2,000 base pairs . The large deletions frequently occurred between two short direct repeat sequences from 2 to 6 base pairs, suggesting that they are generated during the end-joining repair of double-strand breaks induced by interstrand cross-links in DNA . In 6-thioguanine selection, tandem-base substitutions, such as 5'-GG-3' to 5'-AT-3', were induced . It highlights the relevance of intrastrand cross-links as genotoxic lesions . Previous in vitro studies report the induction of single-base substitutions and single-base deletions by MMC . However, no such mutations were identified in vivo . Thus, our results strongly caution that in vitro mutation spectra do not necessarily reflect genotoxic events in vivo and emphasize the importance of transgenic rodent genotoxicity assays to examine the roles of DNA adducts in mutagenesis and carcinogenesis.

Eur J Drug Metab Pharmacokinet, 2002 Oct-Dec, 27(4), 265 - 71
Tissue pharmacokinetics of florfenicol in pigs experimentally infected with Actinobacillus pleuropneumoniae; Li JZ et al.; The aim of this study has been to determine the tissue pharmacokinetic parameters of florfenicol in the pigs experimentally infected with Actinobacillus pleuropneumoniae . 21 crossed-bred (Duroc x Landrace x Yorkshire) local species of pigs were infected experimentally with Actinobacillus pleuropneumoniae serotype 1 and confirmed as typical sub-acute pleuropneumonia . A single dose of 20 mg/kg body weight of florfenicol, a novel animal-using antibiotic, was administrated intramuscularly in the pigs and then samples of blood, lung, trachea with bronchi, liver, kidney and muscle were taken at scheduled time points . Drug concentrations were determined by high performance liquid chromatography (HPLC) with an ultraviolet detector via extraction with ethyl acetate under nitrogen flow . The statistic moment theory (SMT) mathematic package was applied to calculate the tissue pharmacokinetic parameters of florfenicol in the infected model . AUC of lung, trachea with bronchi, liver, kidney and muscle were 121.69, 79.37, 81.05, 181.2, and 94.07 mg/l x h, respectively, MRT were from 34.66 to 90.17 h, and t1/2beta from 24.75 to 69.34 h, respectively . CONCLUSIONS: Florfenicol was widely distributed in these tissues and maintained the effective therapeutic concentrations especially in the respiratory tract tissues that are the target organs of Actinobacillus pneuropneumoniae . CLINICAL SIGNIFICANCE: Tissue pharmacokinetic data could be evidence for regime designing of florfenicol in treatment of porcine pleuropneumonia.

Scand J Infect Dis, 2002, 34(12), 934 - 6
Buttock abscess brucellosis; Dakdouk GK et al.; Human brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations, and its complications can affect almost all organs and systems with varying incidence . Soft-tissue infection due to Brucella species is a rare complication of brucellosis . This report presents a case of a 30-y-old previously healthy woman whose right buttock abscess culture grew Brucella spp . The patient was treated successfully with abscess drainage and antibiotic therapy.

Rev Esp Quimioter, 2002 Dec, 15(4), 341 - 5
{In vitro activity of clarithromycin and metronidazole against Helicobacter pylori in different incubation atmospheres}; Alarcon T et al.; The aim of this study was to determine the in vitro activity of clarithromycin and metronidazole using an agar dilution method to compare two different incubation atmospheres: a CO2 incubator and a jar with a microaerobic gas-generating system . Antibiotics were placed on plates in twofold dilutions ranging from 128 to 0.064 mg/l in Mueller-Hinton agar supplemented with 7% horse blood . The inoculum was prepared from 31 Helicobacter pylori isolates and was inoculated using a Steers replicator . Plates were incubated for 3 to 5 days and MICs were recorded as the lowest concentration of antibiotic inhibiting visible growth . Two different incubation atmospheres were used: a CO2 incubator set at 95% humidity and 10% CO2, and a jar with a gas-generating envelope that produces 7-10% O2 and 14% CO2 (BioMerieux) . Clarithromycin resistance was found in 19% of strains both in the gas-generating system and the CO2 incubator . Metronidazole resistance was 23% in both atmospheres . MICs for clarithromycin in both atmospheres showed two dilutions of difference for 100% of the strains, and were slightly higher in the jar with a gas-generating envelope . However, MICs for metronidazole were higher when it was incubated in the CO2 incubator, and in 86.7% of strains the MICs showed < or = 2 dilutions of difference . No great discrepancies were found for either metronidazole or clarithromycin using the two methods.

Braz J Infect Dis, 2002 Dec, 6(6), 309 - 12
Severe low back pain due to retroperitoneal abscess formation in diabetic patients; Ohmori M et al.; We report two cases of diabetic patients with severe low back pain associated with retroperitoneal abscesses . In the first case, multiple retroperitoneal and spinal epidural abscesses were detected . Paraplegia due to the spinal epidural abscess was not relieved by drainage of the abscess and subsequent antibiotic therapy . In the second case, drainage of the retroperitoneal abscess and antibiotics were immediately started, resulting in successful recovery . Thus, we suggest that if a diabetic patient complains of low back pain, potential abscess formations should be considered and given appropriate treatment before administering epidural anesthetic injections for pain relief.

J Pak Med Assoc, 2002 Nov, 52(11), 497 - 501
Amoebic versus pyogenic liver abscess; Ahsan T et al.; OBJECTIVES: To study the differences between the clinical presentation and complications of amoebic and pyogenic liver abscess . To correlate the diagnostic significance of Entamoeba Indirect Haemagglutination test (E.IHA) in establishing the diagnosis of amoebic liver abscess . DESIGN: Open cohort observational study . SETTING: Department of Medicine (Medical Unit II) Jinnah Postgraduate Medical Centre, Karachi . PARTICIPANTS: Fifty two patients aged 13-70 years admitted in Medical Unit II and diagnosed to have liver abscess . INTERVENTIONS: Group A comprised of patients clinically diagnosed to have amoebic liver abscess and received Metronidazole 500mg iv x 8 hourly for atleast 10 days or more if patient developed complications . Group B comprised of patients diagnosed to have pyogenic abscess and received Cefotaxime 1g iv x 8 hourly for the same duration or more if complicated (antibiotic reviewed in accordance with culture and sensitivity report) . MAIN OUTCOME MEASURES: Differences in the clinical presentation, complications and diagnostic parameters between the two groups of patients . RESULTS: It was not possible to differentiate between amoebic and pyogenic liver abscess on clinical grounds, routine investigations and imaging techniques . Aspiration of pus, especially if the abscess was multiple, was most helpful in differentiating the two types of abscesses . Serological test of E.IHA was highly specific and sensitive for amoebic liver abscess . CONCLUSION: Majority of liver abscesses in Karachi are due to Entamoeba Histolytica . Pyogenic abscess though less frequent, must be excluded by pus aspiration and culture and sensitivity . E.IHA is a good rapid method of discriminating between the two types of abscesses.

Vet Ther, 2002 Winter, 3(4), 441 - 52
Treatment of periodontal pockets with doxycycline in beagles; Zetner K et al.; Following pretreatment with clindamycin, cleaning, scaling, polishing, and curettage, six beagles that were patients at the Dental Department of the Clinic for Surgery and Ophthalmology of the University of Veterinary Medicine of Vienna received a doxycycline polymer filling (Doxirobe, Pharmacia Animal Health) in periodontal pockets of teeth 204, 208, 304, and 309 . Gingivitis index, gingival crevicular fluid, probing depth, and attachment loss were determined before and 6 and 12 weeks after treatment . Teeth 104, 108, 404, and 409 did not receive antibiotic therapy but were pretreated in the same manner as the doxycycline-treated teeth . Pocket depth for teeth treated with doxycycline was significantly reduced (improved) by 39% after 6 weeks (P =.001) and by 35% after 12 weeks (P =.001) . Pockets around control teeth were improved after cleaning and curettage but were still significantly deeper than around teeth treated with doxycycline . Compared with control teeth, teeth treated with doxycycline had significantly less gingival crevicular fluid after treatment (P =.001) . Teeth treated with doxycycline gained significant attachment after 6 (42%) and 12 (38%) weeks . Significantly fewer bacteria were harvested from doxycycline-treated teeth than from control teeth . The gingival index was significantly lower in the doxycycline-treated teeth than in the control teeth 6 (P =.002) and 12 (P =.007) weeks after treatment . Local application of doxycycline complements traditional subgingival curettage therapy in a reasonable and effective way and can significantly improve treatment success, especially with regard to pocket depth reduction and attachment gain.

Toxicol Appl Pharmacol, 2003 Jan 1, 186(1), 46 - 54
M40403, a superoxide dismutase mimetic, protects cochlear hair cells from gentamicin, but not cisplatin toxicity; McFadden SL et al.; Gentamicin, an aminoglycoside antibiotic, and cisplatin, a platinum-based anticancer drug, are two commonly used clinical drugs with ototoxic side effects . The ototoxicity of gentamicin and cisplatin has been linked to the production of reactive oxygen species (ROS), although the specific ROS pathways have not been identified . One ROS that might play a role in ototoxicity is the superoxide radical, which is enzymatically dismutated to molecular oxygen and hydrogen peroxide by endogenous superoxide dismutase (SOD) enzymes . M40403, a manganese-based nonpeptidyl molecule that mimics the activity of SOD, was tested for its ability to protect against gentamicin and cisplatin toxicity in cochlear organotypic cultures from neonatal C57BL/10J mice . Cultures were treated with gentamicin or cisplatin alone or in combination with M40403 . M40403 alone had no effect on outer hair cell (OHC) or inner hair cell (IHC) survival at doses of 1, 5, and 10 microM, but a high dose of 30 microM reduced hair cell numbers by approximately 30% . Gentamicin alone and cisplatin alone killed OHCs and IHCs in a dose-dependent manner . The addition of M40403 to gentamicin-treated cultures significantly increased OHC and IHC survival in a dose-dependent manner, whereas M40403 failed to protect hair cells in cisplatin-treated cultures at any dose . The results suggest that the toxicity of gentamicin and cisplatin to cochlear hair cells are mediated by different pathways . Clinically, increased levels of SOD or SOD mimetics might provide significant protection against aminoglycoside ototoxicity .

Int Orthop, 2003, 27(1), 40 - 6 Epub 2002 Nov 09.
The use of detergent irrigation for musculoskeletal wounds; Anglen JO et al.; The primary purpose of irrigation is to remove bacterial contaminants from the wound . Surfactants do that by disrupting the bonds of the organism to the surface . The use of this wound care strategy was studied in a series of investigations spanning several years . In vitro experiments revealed that surfactant irrigation was superior to saline or antibiotic solutions for removal of adherent bacteria from metallic surfaces, from bone, and from bovine muscle . An in vivo model of the complex orthopedic wound was developed . The superiority of surfactant irrigation over saline or antibiotic solution was demonstrated in animal wounds containing metal, bone injury, and soft tissue damage . Specificity of different surfactant irrigations for various bacterial species was demonstrated . A sequential surfactant irrigation protocol was developed and shown effective in the polymicrobial wound with established infection.

Arch Orthop Trauma Surg, 2003 Feb, 123(1), 39 - 41 Epub 2002 Nov 13.
A report of two cases treated with Pauwels' femoral osteotomy for advanced osteoarthritis resulting from a sequela of infectious coxitis in childhood; Ohsawa S et al.; Pauwels' femoral valgus osteotomy was performed on two osteoarthritic hips that developed as a sequela of infectious coxitis in the childhood . One of the hips was diagnosed as osteomyelitis of the ipsilateral femur before the operation and was treated with curettage and implantation of antibiotic-impregnated cement beads . The results of both hips were excellent and maintained for 9-11 years.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003 Feb, 95(2), 145 - 9
Prophylactic single-dose administration of 600 mg clindamycin versus 4-time administration of 600 mg clindamycin in orthognathic surgery: A prospective randomized study in bilateral mandibular sagittal ramus osteotomies; Lindeboom JA et al.; OBJECTIVE: The purpose of this study was to compare a single 600-mg dose of preoperative intravenously administered clindamycin with a 24-hour 600-mg regimen of clindamycin as prophylaxis for postoperative infections in bilateral sagittal ramus osteotomies . STUDY DESIGN: Seventy patients were assigned at random to an antibiotic protocol . Postoperative infection was assessed by one clinician blinded to the protocol . All data were tabulated, and a statistical analysis was performed by means of the paired t test . RESULTS: In 3 patients, an infection developed . Two of those patients belonged to the single-dose clindamycin group and the other to the 24-hour clindamycin prophylaxis group . The sutures were removed, and wound exudate specimens were obtained for Gram staining and culture . After a 5-day period of 500 mg amoxicillin 4 times daily, the parameters of infection normalized . CONCLUSIONS: There were no statistically significant differences between postoperative infection after the single dose of clindamycin and infection in the 24-hour prophylaxis group (P =.3244).

Yan Ke Xue Bao, 1999 Jun, 15(2), 124 - 6
{Management of infectious endophthalmitis following phacoemulsification}; Cheng B et al.; PURPOSE: To discuss the cause and management of infective endophthalmitis following phacoemulsification . METHODS: Anterior chamber irrigation with anterior chamber drug injection, postoperative systemic and topical antibiotic therapy as well as the use of topical mydriatic agent were applied to 5 of 3,850 eyes which showed endophthalmitis following phacoemulsification . RESULT: All the 5 eyes were saved from infective endophthalmitis . 1 to 5 eyes underwent vitrectomy, 4 of 5 eyes underwent anterior chamber irrigation (wash out) . 4 of 5 eyes had satisfactory visual outcome . One of them had poor visual outcome . CONCLUSION: Preoperative contamination of the anterior chamber is the most common source for pathogenic agents responsible for endophthalmitis following phacoemulsification . Prompt anterior chamber irrigation (washout) with anterior chamber drug injection is one of the effective treatment.

Arch Intern Med, 2003 Feb 10, 163(3), 326 - 32
Improving the quality of care for patients with pneumonia in very small hospitals; Chu LA et al.; BACKGROUND: Despite the publication of guidelines for the management of pneumonia, significant variation in care continues to exist . While there have been several published reports of quality improvement projects for pneumonia, there are few data on the effectiveness of these efforts in small hospitals . The purpose of this study was to demonstrate that a project implemented by a quality improvement organization in small hospitals would lead to an improvement in care that could not be accounted for by secular trends in the management of pneumonia . METHODS: Medicare-insured hospital admissions for pneumonia were reviewed from 20 small hospitals in Oklahoma (intervention group) at baseline and after feedback . Project intervention included onsite feedback presentations to the medical staff, samples of performance improvement materials, and comparative measures of performance of predefined quality indicators . A second group of 16 demographically similar hospitals (control group) was selected for review during the same 2 periods . These hospitals subsequently underwent an identical intervention with a follow-up assessment . RESULTS: Statistically significant improvements in process measures were demonstrated in the intervention hospitals, including performance of a sputum (P<.01) and blood (P<.001) cultures, antibiotic administration within 4 hours of hospital admission (P<.001), and administration of the first dose of antibiotic in the emergency department (P<.001) . These measures in the control hospitals did not change significantly (P =.93, .08, .79, and .52, respectively) during the 2 periods . CONCLUSIONS: Improvements in processes of care achieved by the intervention hospitals resulted from activities initiated because of participation in a quality improvement organization-directed project . This study demonstrated the effectiveness of quality improvement activities in very small hospitals.

Proc Inst Mech Eng {H}, 2003, 217(1), 9 - 12
Fatigue strength of PMMA bone cement mixed with gentamicin and barium sulphate vs pure PMMA; Baleani M et al.; Barium sulphate is added to polymethylmethacrylate (PMMA) bone cement as a radiopacifier . Gentamicin is an antibiotic added to bone cement to treat or prevent infection in arthroplasty . This study investigated the combined effect of barium sulphate and gentamicin sulphate on the fatigue strength of PMMA bone cement . Three different formulations were studied: pure PMMA, PMMA with barium sulphate added and PMMA with barium sulphate and gentamicin sulphate added . Before testing all specimens were stored in water at 37 degrees C for at least 15 days to season the PMMA and to elute the antibiotic . Fatigue tests were performed following a previously validated procedure . The slope part of the Wohler diagram was obtained and a rough endurance limit was estimated for all three formulations . The experimental data showed that the addition of barium sulphate to PMMA bone cement affected the fatigue strength of the material, whereas addition of gentamicin sulphate to the radiopaque PMMA had no effect on the fatigue properties of the bone cement . While PMMA with barium sulphate added was confirmed to have a reduced fatigue strength when compared with plain PMMA, no detrimental effect was found for the addition of gentamicin sulphate to radiopaque PMMA.

Ann Chir Plast Esthet, 2002 Dec, 47(6), 633 - 40
{Our experience with tissue expansion on a series of 50 cases in Vietnam}; Son TT et al.; The authors reviewed their experience with tissue expansion from July of 1995 to December of 1999 at Hanoi Plastic Surgery Center . A total of 75 tissue expanders of various sizes were placed in 50 consecutive patients (16 men and 34 women) for the reconstruction of secondary defects (burn scars, skin graft scars, hypertrophic scars, keloids, capillary hemangioma, congenital nevi and micotia) . The average age of patients was 21 years . The tissue expansion protocol was used in clinical as well as common principle . The main technical details are modified in this procedure by the authors: type of intralesional incision for expander insertion, closing of wound incision by three layers, evacuation of the liquid in the prosthesis pocket, injection with antibiotic solution and expanded flap capsulectomy . The complications rate was 10.6% (8 complications in 75 expanders) . The most common complications consisted of infection, hematoma, exposure of valve, dehiscence of incision, necrosis of the distal expanded flap . The overall failure rate was 8% . Thus our modified surgical details allowed us to decrease the major complications and to achieve the best possible functional and aesthetic results.

Semin Oncol, 2002 Dec, 29(6 Suppl 19), 53 - 6
The potential of amifostine in high-dose chemotherapy and autologous hematopoietic stem cell transplantation; Phillips GL 2nd; Amifostine treatment may allow chemotherapy dose increases beyond those permitted by autologous hematopoietic stem cell transplantation . In a recent study in patients with solid tumors receiving a high-dose regimen of etoposide, ifosfamide, and carboplatin plus autologous stem cell transplantation, amifostine pretreatment was associated with significant reductions in time to neutrophil and thrombocyte engraftment, fewer days of neutropenic fever, less need for salvage antibiotic therapy . Also, there were significant reductions in grade 3 or 4 stomatitis/diarrhea, and delayed nausea/vomiting . A phase I/II study in patients with refractory/high-risk malignancies indicated that a 140% increase of high-dose melphalan (up to 280 mg/m2) can be safely used with amifostine and autologous stem cell transplantation with manageable mucosal toxicity and a reduced incidence of regimen-related toxicity . Preliminary findings in another phase II study indicate that melphalan 280 mg/m2 can also be safely used with amifostine/stem cell transplantation in the treatment of patients with myeloma . Additional studies are ongoing or planned to examine the potential hematoprotective and hematostimulating effects of amifostine in the setting of high-dose chemotherapy and autologous stem cell transplantation .

Chest, 2003 Feb, 123(2), 518 - 23
Microscopic examination of intracellular organisms in protected bronchoalveolar mini-lavage fluid for the diagnosis of ventilator-associated pneumonia; Sirvent JM et al.; STUDY OBJECTIVES: To assess the cutoff percentage of cells containing intracellular organisms (ICOs) in the microscopic examination of mini-lavage fluid for the diagnosis of ventilator-associated pneumonia (VAP), and to study the accuracy of this diagnostic procedure on patients who have received previous antibiotic therapy (AT) . DESIGN: Prospective clinical investigation . SETTING: The medico-surgical ICU of a university hospital . PATIENTS: Eighty-two patients who fulfilled the clinical criteria of first episode of VAP . INTERVENTIONS: Lower airway secretion samples were obtained by a nonbronchoscopic protected bronchoalveolar mini-lavage (mini-PBAL) . Measurements and results: A total of 82 mini-PBALs were performed . The fluid obtained was divided into two samples . The first sample underwent direct microscopic examination using centrifugal cytology and Giemsa stain in order to determine the percentage of cells containing ICOs . The second sample was processed for Gram stain and quantitative cultures . VAP was the final diagnosis in 65 patients based on the mini-PBAL results obtained in the quantitative cultures . At least one bacterial species grew in a significant concentration (> or = 10(3) cfu/mL) . The mini-PBAL was performed on 42 patients during AT (> or = 24 h of effective AT at the time of diagnostic procedure) and on another 40 patients with no AT (No AT) . The results of the quantitative cultures were compared with the percentage of cells containing ICOs using a receiver operator characteristic (ROC) curve . The cutoff point of > or = 2% of cells containing ICOs had the highest sensitivity (80%) and specificity (82%) in the studied population (area under the ROC curve {AUC}, 0.83; 95% confidence interval {CI}, 0.70 to 0.90) . In patients receiving AT, the sensitivity was 70% and specificity was 75% (AUC, 0.73; 95% CI, 0.58 to 0.90); and in No AT-group patients sensitivity was 88% and specificity was 100% (AUC, 0.92; 95% CI, 0.84 to 1.0) . The comparative analysis of both ROC curves was statistically significant (p = 0.04) . CONCLUSIONS: The cutoff point of > or = 2% of cells containing ICOs has the highest sensitivity and specificity in the microscopic examination of mini-lavage fluid for the diagnosis of VAP . However, sensitivity is too low to be clinically useful . The direct examination of mini-PBAL fluid is less accurate when previous AT has been administered.

Anal Biochem, 2003 Feb 1, 313(1), 46 - 52
In situ assay of the intramitochondrial enzymes: use of alamethicin for permeabilization of mitochondria; Gostimskaya IS et al.; The channel-forming antibiotic alamethicin was used to permeabilize mitochondrial membranes for the low molecular mass hydrophilic substrates NADH and ATP . Alamethicin-treated mitochondria show high rotenone-sensitive NADH oxidase, NADH-quinone reductase, and oligomycin-sensitive and carboxyatractylate-insensitive ATPase activities . Alamethicin does not affect Complex I and ATPase activities in inside-out submitochondrial particles . Permeabilized mitochondria quantitatively retain their aconitase and iso-citrate dehydrogenase activities . Electron microscopy of alamethicin-treated mitochondria reveals no disruption of their outer and inner membranes . From the results obtained it is recommended, that alamethicin be used for the in situ catalytic assay of intramitochondrially located enzymes .

Curr Opin Pulm Med, 2003 Mar, 9(2), 117 - 24
Evidence-based approach to acute exacerbations of COPD; Soto FJ et al.; Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and it accounts for approximately 500,000 hospitalizations for exacerbations each year . New definitions of acute COPD exacerbation have been suggested, but the one used by Anthonisen et al . is still widely accepted . It requires the presence of one or more of the following findings: increase in sputum purulence, increase in sputum volume, and worsening of dyspnea . Patients with COPD typically present with acute decompensation of their disease one to three times a year, and 3% to 16% of these will require hospital admission . Hospital mortality of these admissions ranges from 3% to 10% in severe COPD patients, and it is much higher for patients requiring ICU admission . The etiology of the exacerbations is mainly infectious (up to 80%) . Other conditions such as heart failure, pulmonary embolism, nonpulmonary infections, and pneumothorax can mimic an acute exacerbation or possibly act as "triggers." Baseline chest radiography and arterial blood gas analysis during an exacerbation are recommended . Oxygen administration through a venturi mask seems to be appropriate and safe, and the oxygen saturation should be kept just above 90% . Either a short acting beta 2-agonist or an anticholinergic is the preferred bronchodilator agent . The choice between the two depends largely on potential undesirable side effects and the patient's coexistent conditions . Adding a second bronchodilator to the first one does not seem to offer much benefit . The evidence suggests similar benefit of MDIs when compared with nebulized treatment for bronchodilator delivery . If MDIs are to be used, spacer devices are recommended . Steroids do improve several outcomes during an acute COPD exacerbation, and a 10- to 14-day course seems appropriate . Antibiotic use has been shown to be beneficial, especially for patients with severe exacerbation . Changes in bacteria strains have been documented during exacerbations, and newer generations of antibiotics might offer a better response rate . There is no role for mucolytic agents or chest physiotherapy in the acute exacerbation setting . Noninvasive positive pressure ventilation might benefit a group of patients with rapid decline in respiratory function and gas exchange . It has the potential to decrease the need for intubation and invasive mechanical ventilation and possibly decrease in-hospital mortality.

J Clin Microbiol, 2003 Feb, 41(2), 813 - 5
Detection of Helicobacter pylori in paraffin-embedded and in shock-frozen gastric biopsy samples by fluorescent in situ hybridization; Russmann H et al.; We report on the successful application of fluorescent in situ hybridization for detection of Helicobacter pylori and determination of its clarithromycin susceptibility in formalin-fixed and paraffin-embedded gastric biopsy specimens that had been prepared for pathological examination . This method is useful when results from conventional culturing with antibiotic susceptibility testing are not available.

Chem Biol, 2003 Jan, 10(1), 45 - 52
RNA cleavage and inhibition of protein synthesis by bleomycin; Abraham AT et al.; Bleomycin is a clinically used antitumor antibiotic long thought to function therapeutically at the level of DNA cleavage . Recently, it has become clear that bleomycin can also cleave selected members of all major classes of RNA . Using the computer program COMPARE to search the database established by the Anticancer Drug Screening Program of the National Cancer Institute, a possible mechanism-based correlation was found between onconase, an antitumor ribonuclease currently being evaluated in phase III clinical trials, and the chemotherapeutic agent bleomycin . Following these observations, experimentation revealed that bleomycin caused tRNA cleavage and DNA-independent protein synthesis inhibition in rabbit reticulocyte lysate and when microinjected into Xenopus oocytes . The correlation of protein synthesis inhibition to the previously reported site-specific RNA cleavage caused by bleomycin supports the thesis that RNA cleavage may constitute an important element of the mechanism of action of bleomycin.

Diagn Microbiol Infect Dis, 2003 Jan, 45(1), 53 - 61
Detection and drug-susceptibility testing of M . tuberculosis from sputum samples using luciferase reporter phage: comparison with the Mycobacteria Growth Indicator Tube (MGIT) system; Bardarov S Jr et al.; Rapid diagnosis of drug-resistant M.tuberculosis (Mtb) is desirable worldwide . We (i) describe a new luciferase reporter phage (LRP), phAE142 for this purpose; (ii) compare it to the automated MGIT 960 for time-to-detection of Mtb in clinical specimens; and (iii) evaluate its use for species confirmation and antibiotic susceptibility testing(AST) of Mtb . Twenty sputum samples were inoculated for testing by LRP, or by MGIT 960 . After "positives" were identified by either method, the LRP was used for confirmation of Mtb complex (TBC) and for AST . The LRP method proved comparably efficient to MGIT 960 at detecting Mtb . Using an antibiotic uniquely inhibiting TBC with LRP provided species assignment, concurrently with AST, in a median of 3 days, with a sensitivity of 97% . Overall agreement in susceptibility results was 96% . Reliable susceptibility results and identification of TBC can be completed in a median of 12 days (range 8 to 16d) with LRP applied to sputum samples.

Biotechnol Prog, 2003 Jan-Feb, 19(1), 109 - 20
Toward higher order control modalities in mammalian cells-independent adjustment of two different gene activities; Fux C et al.; Heterologous higher order control modalities will be important tools for targeted multigene interventions in next-generation gene therapy, tissue engineering, and sophisticated gene-function studies . In this study, we present the design and rigorous quantitative analysis of a variety of different dual-regulated gene transcription control configurations combining streptogramin- and tetracycline-responsive expression systems in a one-vector format . Quantitative assessment of dual-regulated expression performance in various mammalian and human cell lines is based on two compatible secreted reporter genes, SEAP, the human placental secreted alkaline phosphatase, and the recently developed SAMY, the secreted alpha-amylase . Assembly of streptogramin- and tetracycline-responsive transgene control units in consecutive (--> -->), divergent (<-- -->), and convergent (--> <--) orientation showed excellent regulation characteristics in most genetic arrangements exemplified by neglectable interference and high transgene induction ratios in all four control settings (ON/ON, OFF/ON, ON/OFF, OFF/OFF) . The overall regulation performance of divergent dual-regulated expression configurations could be substantially increased when placing noncoding stuffer fragments or insulator modules between the divergently oriented antibiotic-responsive promoters . Dual-regulated expression technology pioneers artificial higher order gene control networks that will likely enable new opportunities in multigene metabolic engineering and generate significant therapeutic impact.

Int J Qual Health Care, 2002 Dec, 14 Suppl 1, 35 - 45
The role of research in developing job aids for pneumonia treatment in Niger; Edson WN et al.; OBJECTIVE: To use qualitative research to develop a complementary set of job aids to improve adherence to cotrimoxazole for childhood pneumonia and to improve provider-client counseling . DESIGN: Qualitative research on existing knowledge and practices of parents and providers using key informant interviews, focus groups, clinic observation, and home visits . A workshop of local stakeholders produced messages and job aids for health care workers and parents that included counseling cards and posters for providers, and medication envelopes with educational messages for mothers . Draft mock-ups were tested, modified, and re-tested before final production and distribution . SETTING: Boboye District, Niger . STUDY PARTICIPANTS: Clinic health care workers, mothers of children with pneumonia, and key informants . RESULTS: A complementary set of counseling tools, or job aids, was designed based on consensus developed during the workshop, leading to greater buy-in and local support . CONCLUSION: Behavior change communication theory and qualitative research can be applied to the design of key messages on adherence to an antibiotic regimen and corresponding job aids for both parents and health care workers . This approach generates enthusiastic support from local participants.

Mycoses, 2002 Oct, 45(8), 287 - 94
The value of the chest computed tomography halo sign in the diagnosis of invasive pulmonary aspergillosis . An autopsy-based retrospective study of 48 patients; Kami M et al.; To evaluate the diagnostic value of a halo on computed tomography (CT) in the diagnosis of invasive pulmonary aspergillosis (IPA), we retrospectively reviewed chest CT scans and autopsy reports for patients who had been admitted to our hospitals for the treatment of hematological malignancy . Pulmonary complications were suspected in all patients and chest CT scans were taken within a month of death . We examined the association between autopsy and CT findings in 48 patients who were diagnosed as IPA (n = 17), candidosis (n = 4), zygomycosis (n = 2), infiltration of hematological malignancy (n = 12), bacterial pneumonia (n = 6), cytomegalovirus pneumonia (n = 2), pulmonary hemorrhage (n = 2), or pulmonary congestion (n = 1) . Patients with IPA showed a variety of CT findings, including halo (n = 13), nodules (n = 14), granular shadows (n = 3), masses (n = 6), consolidations (n = 9), wedge-shaped consolidations (n = 1), and cavitation (n = 2) . In contrast, 0, 11 and two of the 31 patients without IPA showed halo, nodules and masses, respectively . These signs were more frequently observed in IPA patients than in non-IPA patients . The CT halo, especially, seemed to be specific for IPA in hospitalized neutropenic patients with hematological malignancies who developed antibiotic-resistant fever . For CT findings other than these three signs, there were no significant differences between IPA- and non-IPA patients.

Dent Update, 2002 Dec, 29(10), 498 - 503
A practical guide for patients undergoing exodontia following radiotherapy to the oral cavity; Kanatas AN et al.; Dental extractions or minor oral surgery in patients who have undergone radiation therapy for cancer in the head and neck carry the risk of one of the most serious and devastating complications of head and neck radiotherapy, that of osteoradionecrosis (ORN) . A totally unified approach to dental extractions following radiotherapy is lacking . The role of the general dental practitioner in management of patients following radiotherapy is crucial . Contrary to clinical impression, the risk of ORN does not decrease with time . When contemplating exodontia or minor oral surgery in the irradiated patient, special consideration should be given to issues such as radiotherapy history, surgical assessment, surgical procedure and the role of antibiotics and hyperbaric oxygen.

Appl Environ Microbiol, 2003 Feb, 69(2), 1263 - 9
Cloning and analysis of a DNA fragment stimulating avermectin production in various Streptomyces avermitilis strains; Hwang YS et al.; To isolate a gene for stimulating avermectin production, a genomic library of Streptomyces avermitilis ATCC 31267 was constructed in Streptomyces lividans TK21 as the host strain . An 8.0-kb DNA fragment that significantly stimulated actinorhodin and undecylprodigiosin production was isolated . When wild-type S . avermitilis was transformed with the cloned fragment, avermectin production increased approximately 3.5-fold . The introduction of this fragment into high-producer (ATCC 31780) and semi-industrial (L-9) strains also resulted in an increase of avermectin production by more than 2.0- and 1.4-fold, respectively . Subclones were studied to locate the minimal region involved in stimulation of pigmented-antibiotic and avermectin production . An analysis of the nucleotide sequence of the entire DNA fragment identified eight complete and one incomplete open reading frame . All but one of the deduced proteins exhibited strong homology (68 to 84% identity) to the hypothetical proteins of Streptomyces coelicolor A3(2) . The orfX gene product showed no significant similarity to any other protein in the databases, and an analysis of its sequence suggested that it was a putative membrane protein . Although the nature of the stimulatory effect is still unclear, the disruption of orfX revealed that this gene was intrinsically involved in the stimulation of avermectin production in S . avermitilis.

Cytotherapy, 2002, 4(6), 531 - 8
GM-CSF versus G-CSF: engraftment characteristics, resource utilization, and cost following autologous PBSC transplantation; Zumberg MS et al.; BACKGROUND: G-CSF and GM-CSF have both been shown to decrease the time to hematopoietic recovery when administered after autologous BM or peripheral stem cell re-infusion . However, few studies have compared G-CSF and GM-CSF to determine which is the preferred myeloid growth factor . METHODS: This study compares a prospectively accrued cohort of 22 patients receiving GM-CSF with a historical cohort of patients who received G-CSF commencing Day + 6 after autologous PBSC transplantation . Patients were matched based on disease type and stage, CD34(+) cell dose/kg, conditioning regimen, and prior treatment . Time to myeloid engraftment, growth factor utilization, antibiotic utilization, fever incidence, and cost were compared . RESULTS: The median time to neutrophil and platelet engraftment was similar in the two groups (ANC > 500 /mm(3), GM-CSF 12 versus G-CSF 11, P = 0.69) . There was a trend towards more days of temperature > 38.0 masculine C (six versus three, P = 0.05) and febrile neutropenia (three versus two, P = 0.06) in the GM-CSF arm . There was a trend towards increased use of i.v . antibiotics in the GM-CSF cohort (7.6 days versus 5.5 days, P = 0.06) . More chest X-rays (1.5 versus 1.0, P = 0.03) were ordered, and more blood cultures drawn (4.2 versus 2.7, P = 0.05) as part of fever evaluation in the group treated with GM-CSF . Resource utilization based on actual wholesale pricing (AWP) favored the G-CSF cohort . Applying a sensitivity analysis, GM-CSF became cost-effective when priced below $94 per 250 micro g, despite greater resource utilization . DISCUSSION: This study suggests that engraftment characteristics are similar with GM-CSF and G-CSF following PBSC transplantation . Resource utilization for fever treatment and evaluation may be greater with GM-CSF . Determination of which agent is more cost-effective depends on institutional acquisition costs.

J Assoc Physicians India, 2002 Oct, 50, 1324 - 6
Unilateral pulmonary agenesis with ipsilateral musculoskeletal anomalies; Aggarwal AN et al.; A young patient with right pulmonary agenesis is described . She presented with left pneumonitis and improved with antibiotic therapy . She additionally had absence of right thumb and reduced muscle mass over right side of face . The anomalies may have resulted from an antenatal insult around the fourth week of embryonic development.

Clin Infect Dis, 2003 Feb 15, 36(4), 399 - 406 Epub 2003 Jan 30.
Respiratory tract infections in travelers: a review of the GeoSentinel surveillance network; Leder K et al.; Respiratory tract infections are common in travelers, and improving our knowledge of risk factors associated with specific types of respiratory infections should enable implementation of better preventive strategies . Data collected by the GeoSentinel surveillance network were analyzed, and the most significant predictors for developing specific categories of respiratory infections while abroad were age, sex, season of travel, trip duration, and reason for travel . In particular, influenza was associated with travel to the Northern Hemisphere during the period of December through February, travel involving visits to friends or relatives, and trip duration of >30 days . Lower respiratory tract infections were associated with male sex and increasing age . Knowledge of the respiratory tract infections that occur in specific groups of travelers allows for the development of targeted pretravel preventive strategies to high-risk groups.

Pharmacology, 2003 Feb, 67(2), 55 - 8
Trypanosoma cruzi: in vitro morphological alterations induced by actinomycin D; Zaverucha do Valle T et al.; Actinomycin (ActD) is an antibiotic that binds DNA, preventing transcription . When a Trypanosoma cruzi infection in mice is treated with this drug, the parasite loses its ability to multiply, enabling protection . In this study, axenic cultured T . cruzi parasites were exposed to different concentrations of ActD (10, 20, and 50 microg/ml), all of them being able to inhibit growth and to alter the mobility . Nevertheless, the parasites remained alive and motile for at least 14 days . Scanning electron microscopy of trypomastigotes treated with 10 microg/ml of ActD for 24 h showed a modification in their morphology which suggests a change in the parasite cytoskeleton .

Biochemistry, 2003 Feb 11, 42(5), 1186 - 98
New complex of post-activated neocarzinostatin chromophore with DNA: bulge DNA binding from the minor groove; Kwon Y et al.; Neocarzinostatin (NCS-chrom), a natural enediyne antitumor antibiotic, undergoes either thiol-dependent or thiol-independent activation, resulting in distinctly different DNA cleavage patterns . Structures of two different post-activated NCS-chrom complexes with DNA have been reported, revealing strikingly different binding modes that can be directly related to the specificity of DNA chain cleavage caused by NCS-chrom . The third structure described herein is based on recent studies demonstrating that glutathione (GSH) activated NCS-chrom efficiently cleaves DNA at specific single-base sites in sequences containing a putative single-base bulge . In this structure, the GSH post-activated NCS-chrom (NCSi-glu) binds to a decamer DNA, d(GCCAGAGAGC), from the minor groove . This binding triggers a conformational switch in DNA from a loose duplex in the free form to a single-strand, tightly folded hairpin containing a bulge adenosine embedded between a three base pair stem . The naphthoate aromatic moiety of NCSi-glu intercalates into a GG step flanked by the bulge site, and its substituent groups, the 2-N-methylfucosamine carbohydrate ring and the tetrahydroindacene, form a complementary minor groove binding surface, mostly interacting with the GCC strand in the duplex stem of DNA . The bulge site is stabilized by the interactions involving NCSi-glu naphthoate and GSH tripeptide . The positioning of NCSi-glu is such that only single-chain cleavage via hydrogen abstraction at the 5'-position of the third base C (which is opposite to the putative bulge base) in GCC is possible, explaining the observed single-base cleavage specificity . The reported structure of the NCSi-glu-bulge DNA complex reveals a third binding mode of the antibiotic and represents a new family of minor groove bulge DNA recognition structures . We predict analogue structures of NCSi-R (R = glu or other substituent groups) may be versatile probes for detecting the existence of various structures of nucleic acids . The NMR structure of this complex, in combination with the previously reported NCSi-gb-bulge DNA complex, offers models for specific recognition of DNA bulges of various sizes through binding to either the minor or the major groove and for single-chain cleavage of bulge DNA sequences.

Curr Med Res Opin, 2002, 18(8), 520 - 2
Comparative efficacy of two anti-bacterial/anti-inflammatory formulations (Auricularum otic powder and Dex-Otic drops) in the medical treatment of otitis externa; Yaniv E et al.; BACKGROUND: Otitis externa (OE) is a common disorder which can cause severe pain and discomfort with discharge and hearing loss . The majority of topical preparations for OE treatment contain a combination of steroids and antibiotics and are administered as ear drops . Otic powder preparations are less common . We found no studies which compared the efficacy of the two dosage forms . OBJECTIVE: The purpose of the study was to compare the healing process of the external ear canal when treated locally either with otic powder (Auricularum), a preparation containing antibiotic, steroidal and antimycotic components, or with otic drops (Dex-Otic), a commercial ear drop preparation containing antibiotic and steroidal components . METHODS: The study was designed as an open, randomised, comparative clinical trial . Ambulatory patients suffering from OE were examined by an ear specialist and randomly divided into an otic powder (Auricularum) treatment group and an ear drop (Dex-Otic) treatment group . Each treatment group was treated in accordance with the daily doses recommended by the manufacturers . Patients were treated for a period of 14 days and examined on days 0, 3, 7, 10 and 14 . Clinical signs and symptoms recorded were pain, erythema, swelling and discharge . RESULTS: A total of 67 patients entered the study . The probability of healing within 7 days was 74% in the otic powder group as opposed to 40% in the ear drops group (log rank test, p = 0.0013) . The probability of total pain relief after 3 days of treatment was 60% in the otic powder group compared to 53% in the ear drops group (log rank test, p = 0.0001) . CONCLUSION: We conclude that treatment with an otic powder (Auricularum) may promote earlier healing and pain relief than does treatment with otic drops (Dex-Otic).

Farmaco, 2002 Dec, 57(12), 993 - 7
Synthesis of oxathiolane imidazole nucleosides; Kocabalkanli A et al.; Nucleosides have been of great interest since their strong antiviral activities were discovered . 1,3-Oxathiolane ring system has been known for many years, but it is in recent years that the ring has been used as the sugar ring in nucleoside analogs (Synthesis (1991) 1046; J . Am . Chem . Soc . 113 (1991) 9377; Tetrahedron Lett . 35 (1994) 4739) . Besides, bredinin is a natural nucleoside antibiotic with imidazole moiety and there are some other studies reported on nucleosides with the imidazole group (Biorg . Med . Chem . 7 (1999) 481; Biorg . Med . Chem . 7 (1999) 1617; Nucleosides Nucleotides 18 (1999) 331) . These findings make the imidazole group interesting as the base of a nucleoside . In this study, in order to find out the structure-activity relationships of L-oxathiolanyl nucleosides, L-oxathiolanyl imidazole nucleosides 7 and 8 were synthesized, via novel intermediates 2-6, which were then tested for anti-HIV activity (Antivir . Res . 1-11 (1994) 25) in human peripheral blood mononuclear (PBM) cells, the synthesized nucleosides did not show significant activity up to 100 microM against HIV-1.

Pediatrics, 2003 Feb, 111(2), 231 - 6
Misconceptions about colds and predictors of health service utilization; Lee GM et al.; OBJECTIVE: Colds accounted for 1.6 million emergency department (ED) visits and 25 million ambulatory visits by children and adults in 1998 . Although most colds are caused by viruses and do not require medical intervention, many families seek health care for the treatment of colds . Parental misconceptions about the cause and appropriate treatment of colds may contribute to unnecessary health service utilization . The objective of this study was to determine predictors of reported ED use and ambulatory care use for colds among families with young children . METHODS: This study was an observational, prospective cohort study to determine attack rates for respiratory illnesses within families that have at least 1 child who is 6 months to 5 years of age and enrolled in out-of-home child care . Families were randomly selected from 5 pediatric practices in Massachusetts and were considered eligible when the child was enrolled in child care with at least 5 other children for >or=10 hours per week . Enrolled families were asked to complete a survey that assessed knowledge about colds, antibiotic indications, and frequency of health service utilization . Predictors of self-reported use of health care services were assessed in multivariate logistic regression models . RESULTS: Of the 261 families enrolled in the study, 197 families (75%) returned completed surveys . Although 93% of parents understood that viruses caused colds, 66% of parents also believed that colds were caused by bacteria . Fifty-three percent believed that antibiotics were needed to treat colds . Parents reported that they would visit the ED (23%) or their doctor's office (60%) when their child had a cold . Predictors of ED use on multivariate analysis included Medicaid insurance (odds ratio {OR}: 17.6 {2.2-139.3}), history of wheezing (OR: 18.3 {4.4-75.8}), and belief that antibiotics treat colds (OR: 4.2 {1.4-12.9}) . Predictors of ambulatory care use included parent younger than 30 years (OR: 10.0 {1.6-64.3}), history of wheezing (OR: 5.6 {1.1-29.7}), and belief that antibiotics treat colds (OR: 3.8 {1.7-8.5}) . CONCLUSIONS: Misconceptions about the appropriate treatment of colds are predictive of increased health service utilization . Targeted educational interventions for families may reduce inappropriate antibiotic-seeking behavior and unnecessary health service utilization for colds.

J Bacteriol, 2003 Feb, 185(4), 1465 - 9
The periplasmic protein MppA requires an additional mutated locus to repress marA expression in Escherichia coli; Bina X et al.; Escherichia coli strain TP985, which has an insertional mutation in the gene for the periplasmic murein tripeptide binding protein MppA, was previously reported to overproduce MarA and exhibit a multiple-antibiotic resistance (Mar) phenotype (H . Li and J . T . Park, J . Bacteriol . 181:4842-4847, 1999) . We found that TP985 contained a previously unrecognized marR mutation which was responsible for the Mar phenotype . Transduction of the mppA mutation from TP985 to another wild-type strain did not affect antibiotic susceptibility . Overproduction of MppA repressed marA transcription in TP985 but not in other mppA or marR mutants . Therefore, TP985 contains an additional unknown mutation(s) that facilitates the repression of marA expression by MppA.

J Neurochem, 2003 Feb, 84(4), 633 - 42
Inhibition of NADH oxidation by chloramphenicol in the freely moving rat measured by picosecond time-resolved emission spectroscopy; Mottin S et al.; Owing to the lack of methods capable to monitor the energetic processes taking place within small brain regions (i.e . nucleus raphe dorsalis, nRD), the neurotoxicity of various categories of substances, including antibiotics and psycho-active drugs, still remains difficult to evaluate . Using an in vivo picosecond optical spectroscopy imaging method, we report that chloramphenicol (CAP), besides its well-known ability to inhibit the mitochondria protein synthesis, also influences the NADH/NAD+ redox processes of the respiratory chain . At a 200-mg/kg dose, CAP indeed produces a marked increase in the fluorescent signal of the nRD which, according to clear evidence, is likely to be related to the NADH concentration . This effect also implies an efficient inhibition of complex I of the respiratory chain by CAP . It refers to the mechanism through which the adverse effects of the antibiotic may take place . It could explain why paradoxical sleep, a state needing aerobic energy to occur, is suppressed after CAP administration . The present approach constitutes the first attempt to determine by fluorescence methods the effects of substances on deep brain structures of the freely moving animal . It points out that in vivo ultrafast optical methods are innovative and adequate tools for combined neurochemical and behavioural approaches.

Clin Exp Immunol, 2003 Feb, 131(2), 268 - 74
Benzylpenicillin differentially conjugates to IFN-gamma, TNF-alpha, IL-1beta, IL-4 and IL-13 but selectively reduces IFN-gamma activity; Brooks BM et al.; It is known that beta-lactam antibiotics can conjugate to lysine and histidine residues on proteins via the carbonyl group of the opened beta-lactam ring . However, it is not known which proteins these drugs target and there is little work addressing whether conjugation is preferential for some proteins over others or if conjugation has functional consequences for the protein . We have previously shown that the beta-lactam antibiotic benzylpenicillin (BP) conjugates to IFN-gamma and reduces its activity . This interaction demonstrates selectivity, as BP does not bind to IL-4 . Here, we extend our study to include other Th1 and Th2 cell-associated cytokines and two cytokines associated with inflammatory responses . We demonstrate by Western blotting that BP also conjugates to IL-1beta, IL-2, IL-5, IL-13 and TNF-alpha but not to IL-10 . Densitometric analysis of leading cytokine bands on blots revealed that IFN-gamma always gave more intense BP-positive bands than any other cytokine analysed . Cytokines pre-incubated with BP at 37 degrees C in a protein-containing, serum-free medium were assayed for their biological activity . By in vitro bioassay, BP inhibited the ability of IFN-gamma but not IL-1beta or TNF-alpha to induce CD54 expression on epithelial cells . In addition, BP did not affect IL-4 or IL-13 inhibition of mast cell proliferation . When the pre-incubation temperature was reduced to 4 degrees C, BP did not conjugate to IFN-gamma or modulate its activity . BP retained its inhibitory effect on IFN-gamma activity when 20% FCS was added to the pre-incubation medium . In conclusion, BP conjugates to some cytokines but not others and this does not appear to be related to primary protein structure . Furthermore, of the cytokines studied, conjugation only to IFN-gamma is accompanied by inhibition of activity . This phenomenon is temperature dependent and occurs in the presence of serum . These findings provide further evidence for differential, direct drug-cytokine interactions . Such interactions may have therapeutic implications in terms of targeting cytokines to regulate their activity.

Arch Pathol Lab Med, 2003 Feb, 127(2), 224 - 6
Nocardiosis with brain abscess due to an unusual species, Nocardia transvalensis; Yorke RF et al.; The identification of Nocardia transvalensis, an unusual and probably underrecognized cause of nocardial infection, is clinically significant because of this species' resistance to aminoglycosides, a standard antinocardial therapy . Diagnosis requires analytic methods available predominately in reference laboratories . We report a case of disseminated infection with N transvalensis with primary pulmonary involvement and subsequent development of brain abscesses, and review the literature to date . Familiarity with the epidemiology, pathologic findings, and clinical significance of this and other unusual Nocardia species may increase early identification and antibiotic susceptibility testing in cases of nocardial infection.

Probl Tuberk, 2002, (7), 15 - 8
{Results of surgical treatment in patients with drug-resistant tuberculosis}; Frolov GA et al.; Analysis of the results of surgical treatment in 105 patients with pulmonary tuberculosis revealed that 25 patients had postoperative complications . Complications, outcomes, dysfunctions, and life quality were analyzed in late postoperative periods after 4 types of operations: segmentectomy (n = 52), lobectomy (n = 26), pulmonectomy (n = 12), palliative operations (n = 15) . The best immediate and long-term results were achieved after segmentectomy in patients with antibiotic-sensitive forms of MBT.

Yi Chuan Xue Bao, 2002 Oct, 29(10), 860 - 4
{Establishment of mouse ZF-12+/- embryonic stem cells}; Li JZ et al.; By using the mouse zinc finger protein gene ZF-12 genomic DNA fragment, pSSC-TV-10.5 was designed and constructed as a replacement vector . Structure of pSSC-TV-10.5 was identified by restrictive digestion analysis and partly sequencing . Then linearized vector was electroporated into ES cells, and transfected cells were screened by G418 and GANC selection . Among 508 G418r/GANCr colonies, 4 were proved to have taken place the homologous recombination of ZF-12 by PCR and southern blotting analysis . This study lays the foundations of preparing mouse models of ZF-12+/- or ZF-12-/-.

Izv Akad Nauk Ser Biol, 2002 Nov-Dec, (6), 645 - 9
{Cytotoxic activity of dammarane triterpenoids from birch leaves}; Prokof'eva NG et al.; Cytotoxic activity of dammarane triterpenoids isolated from beach leaves was studied . These substances differ from the native ginseng genin (20(S)-protopanaxadiol) by the number, location, or configuration of OH-groups . Using fertilized egg cells of sea urchin Stronglyocentrotus intermedius we demonstrate that the orientation of C-3 OH-group has no effect on cytotoxic activity of triterpenoids as well as a higher activity of a triterpenoid with 3 alpha,12 beta-OH as compared to a C-3 ketone but lower activity as compared to a triterpenoid with 3 alpha,17 alpha-OH . Depending on the number of OH-groups the cytotoxic activity of triterpenoids decreases in the row: tetraol > pentaol > triol . Dammar-24-ene-3 alpha 2 beta,17 alpha,20(S)-tetraol (compound IV) is cytotoxic for the Ehrlich ascite carcinoma cells and this effect is additive to cytotoxic activity of anthracycline antibiotic carminomycin in vitro . Compound IV changes the permeability and microviscosity of the tumor cell membranes.

Plast Reconstr Surg, 2003 Feb, 111(2), 753 - 60; discussion 761-2
The simple and effective choice for treatment of chronic calcaneal osteomyelitis: neurocutaneous flaps; Yildirim S et al.; The authors describe their experience with the use of distally based saphenous and sural neurofasciocutaneous flaps for the treatment of calcaneal osteomyelitis in nine cases . Aggressive debridement of all nonviable and poorly vascularized tissue and coverage with a distally based neurofasciocutaneous flap were coupled with a thorough antibiotic course in all cases . The deepithelized peripheral parts of all flaps were buried in the bone cavities after bone debridement . Follow-up periods ranged from 15 to 27 months . All flaps survived completely . All of the wounds except one healed completely . These flaps have adequate blood flow for the management of chronic bone infections . They also have many advantages, such as easy quick elevation, short operative time, and acceptable donor-site morbidity . Moreover, patients treated with neurocutaneous flaps do not require debulking procedures or special shoes . Reconstruction with neurocutaneous flaps after radical debridement is a versatile alternative to the use of local or distant muscle flaps and calcanectomy procedures for patients with osteomyelitis of the os calcis.

Medicina (Kaunas), 2002, 38 Suppl 2, 176 - 80
{The first clinical experience and technical peculiarities of mitral valve homograft implantation}; Benetis R et al.; INTRODUCTION . Surgical interventions because of mitral valve disease have been ascribed since 1951 . Many changes within mitral valve replacement have passed including closed and open mitral commissurotomy, mitral valve repair operations implantation of mechanical, biological heart valve and finally use of mitral valve homograft . Despite changes in chirurgical tactics and medico-technical environment, mitral valve homograft implantation remains one of the most complex surgical interventions . Surgical and technical details of mitral valve homograft implantation are discussed . OBJECTIVE . to estimate technical difficulties and anatomical positioning of mitral valve homograft considering a spectrum of indications of mitral valve replacement . CASE REPORT . 62-year-old woman 26 years ago underwent mitral valve replacement with Starr-Edwards mitral valve prosthesis, because of rheumatic heart disease by homograft . Due to malfunction of the mitral valve prosthesis, and progressive left ventricular failure patient was reoperated on 26(th) of February 2002 . Fresh antibiotic preserved mitral valve homograft was implanted . Surgical techniques were guided using left ventricle size measurement indicated by echocardiography . RESULTS . The technique described by Acar/Carpentier was used except of mitral valve annuloplasty ring implantation . Peri- and early postoperative period was free of homograft related complications . The left ventricle function was improving and the heart size decreased dramaticaly during first postoperative week . CONCLUSION . The most important peculiarities for mitral valve homograft implantation are echocardiography data and intraoperative left ventricle measurements . Homograft implantation techniques are rather demanding therefore indications for mitral valve replacement have to be selected carefully and should be based on the presence of severe mitral valve dysfunction in order to achieve best hemodynamic results and prevent patient from anticoagulation therapy.

Blood, 2003 Jun 1, 101(11), 4561 - 8 Epub 2003 Jan 30.
Tetrocarcin-A--induced ER stress mediates apoptosis in B-CLL cells via a Bcl-2--independent pathway; Anether G et al.; Tetrocarcin-A (TC-A), an antibiotic agent isolated from actinomycetes, has recently been described to antagonize Bcl-2 functions, thereby sensitizing tumor cells to cell death signals under control of Bcl-2 . In this study, we analyzed the direct proapoptotic effect of TC-A in the B-chronic lymphocytic leukemia (B-CLL) model . We focused on the signal cascade triggered by TC-A in B-CLL cells and identified activated mitochondrial as well as endoplasmatic reticulum (ER) stress signals . The expression levels of known effector molecules mediating mitochondrial signaling, such as Bax and Bid, and the antagonistic molecule Bcl-2 did not influence sensitivity of B-CLL cells to TC-A . Furthermore, the molecular chaperone and sensor of ER stress, HSP70, though significantly up-regulated in B-CLL cells undergoing TC-A-triggered apoptosis, was ineffective to exert its anti-apoptotic function described in multiple cell death pathways . Autologous T cells of B-CLL patients were significantly less sensitive to TC-A as were also T cells from healthy donors when compared with their normal B-cell fraction . Furthermore, sensitivity of B-CLL cells to TC-A treatment in vitro was dependent neither on the expression levels of CD38-a prognostic factor for survival of B-CLL patients as well as for their response to therapy-nor on the clinical stage or pretreatment status of patients . From our data showing that TC-A induced a cell death pathway via ER stress preferentially in B cells and that it acted independently of important markers of drug sensitivity and of clinical markers, we conclude that TC-A might represent an attractive candidate drug for further evaluation in preclinical trials.

J Pharm Biomed Anal, 2003 Feb 5, 31(1), 11 - 8
Determination of potassium ions in pharmaceutical samples by FIA using a potentiometric electrode based on ionophore nonactin occluded in EVA membrane; Garcia CA et al.; A simple and rapid method was developed for the K(+) ions determination employing a flow injection system using a flow-through electrode based on the naturally-occurring antibiotic ionophore nonactin occluded in a polymeric membrane . The nonactin ionophore was trapped in poly(ethylene-co-vinyl acetate) (EVA) matrix (40% w/w in vinyl acetate) and dispersed on the surface of a graphite-epoxy tubular electrode . The plasticizer-free all-solid-state potassium-selective electrode showed a linear response for K(+) concentrations between 5.0 x 10(-5) and 5.0x10(-2) M (r=0.9995) with a near-Nernstian slope of 51.5 mV per decade, when Tris-HCl buffer (pH 7.0;0,1 M) was employed as a carrier . The potentiometric-FIA system allows an analytical frequency of 120 samples per hour with a precision of 3.6% . The relative standard deviations (R.S.D.) for K(+) determination in pharmaceuticals samples, without any previous treatment, were lower than 4.0%, comparable to those obtained by flame photometry . Ammonium is the main analytical interference and the electrode response time was 5 s at 25 degrees C . The useful lifetime of the tubular sensor is longer than 3 months in continuous use.

Urology . 2003 Jan;61(1):224.
Ureteral obstruction and reconstruction in pelvic actinomycosis; Bercovich A et al.; We present a case of ureteral obstruction secondary to pelvic actinomycosis . Despite stenting, prolonged antibiotic therapy, and debridement, the patient required ureteral resection and reconstruction . This condition may simulate advanced malignancy, and diagnostic suspicion lessens the need for radical extirpative surgery.

Gastroenterology, 2003 Feb, 124(2), 537 - 43
Consecutive regression of concurrent laryngeal and gastric MALT lymphoma after anti-Helicobacter pylori therapy; Caletti G et al.; The most common primary lymphoma of the gastrointestinal tract is B-cell lymphoma arising from mucosa-associated lymphoid tissue known as MALT lymphoma . Although the majority of these lesions affect the stomach and are associated with Helicobacter pylori organisms, sites other than the gastrointestinal tract may be affected . This case report describes a patient with concomitant laryngeal MALT lymphoma and Helicobacter pylori-related gastric MALT lymphoma derived from the same clone as confirmed by PCR . Treatment of Helicobacter pylori infection in this patient using antibiotics led to regression of both lesions . This patient remains in remission at 46-month follow-up . This is the first case report on the regression of a laryngeal MALT lymphoma after Helicobacter pylori eradication . We suggest that all patients presenting with extragastric MALT lymphoma should undergo upper gastrointestinal endoscopy with gastric biopsies for the determination of Helicobacter pylori status and presence of concomitant gastric MALT lymphoma, followed by a course of anti-Helicobacter pylori antibiotic therapy . Nonresponders may subsequently be considered for surgery and/or chemo/radiation therapy.

Eur J Clin Nutr, 2002 Dec, 56 Suppl 4, S39 - 43
Asthma and allergic diseases: is there a downside to cleanliness and can we exploit it?
Crane J.
When hay fever was first described in the early 19th century it was an uncommon disorder . Since then asthma, allergic rhinitis and eczema, have become common conditions particularly in industrialised western economies . International prevalence studies reveal wide variation in the prevalence of asthma, and allergic disease, but confirm this view although the studies also show these diseases to be by no means rare in most countries . The reasons remain unclear but the "hygiene hypthesis" postulating an inverse relationship between hygiene, in its broadest sense, and allergic disease, fits some of the epidemiology of these diseases and has an associated immunological hypthesis to support it . Recent studies suggest that many hygiene related factors may influence immune development in favour of an allergic phenotype . Antibiotics in the first of life have been associated with increased risks of allergic disease in later childgood, and farming exposures to protection . Interest in hte role of bowel flora in modifying immune development has been suggested as an explanation for the risk associated with antibiotic exposure and has led to studies exploring the effects of modifying bowel flora with probiotics both to influence established allergic disease and to prevent it . The challenge is to continue to reap the enormous benefits that accrued from modifying infectious disease by both public and individual health strategies but at the same time convincing the immune system that it has been exposed to them.

Gastrointest Endosc, 2003 Feb, 57(2), 178 - 82
Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study; Kaassis M et al.; BACKGROUND: The systematic use of metal stents to treat biliary obstruction is restricted by high cost compared with plastic stents . The aims of this study were to compare cost and efficacy of plastic stents and metal stents in the treatment of patients with malignant common bile duct strictures and to define factors that predict survival of these patients . METHODS: One hundred eighteen patients (mean age 75 years) with malignant strictures of the common bile duct were randomized to placement of a plastic stent or metal stent . Comparisons were made with the Mann-Whitney or chi-square test as indicated; survival rates were compared with a Cox proportional hazards model . RESULTS: There was no significant difference in survival between the two groups . Time to first obstruction was longer for patients in the metal stent group (metal stent, median not reached vs . plastic stent, 5 months; p = 0.007) . The number of additional days of hospitalization, days of antibiotic therapy, and the numbers of ERCPs and transabdominal US procedures was significantly higher in the plastic stent group . After multivariate analysis, only the presence of liver metastases was independently related to survival (p < 0.0005; OR = 2.25) . This variable defined a group with a shorter survival . Median survival of patients with hepatic metastasis at diagnosis was 2.7 months compared with 5.3 months for patients without liver metastasis; in the latter group, the overall cost associated with metal stents was lower than for plastic stents . CONCLUSIONS: Metal stent placement is the most effective treatment of inoperable malignant common bile duct stricture . Placement of a metal stent is cost effective in patients without hepatic metastases, whereas a plastic stent should be placed in patients with spread of the tumor to the liver.

Medicina (Kaunas), 2002, 38 Suppl 1, 36 - 41
{Chronic prostatitis with chronic pelvic pain syndrome}; Balvocius A; Almost 10% of the adult male population suffer from prostatitis . The International Prostatitis Collaborative Network has devised and validated a clinically useful classification of prostatitis that urologists and primary care clinicians will find helpful . According to this schema, chronic bacterial prostatitis is clearly an infectious disease, and patients with chronic prostatitis associated with chronic pelvic pain syndrome can have either inflammatory or noninflammatory disease . Chronic bacterial prostatitis is uncommon, chronic nonbacterial prostatitis (CPPS) is extremely common . Antibiotic therapy is indicated in management of chronic bacterial prostatitis and inflammatory chronic pelvic pain syndrome . Fluoroquinolones are safe and effective in managing chronic bacterial prostatitis . Based on literature, noninflammatory chronic pelvic pain syndrome can be treated using adrenergic blockade, analgesic, tricyclic antidepressants, benzodiazepie, physical therapy.

Respir Med, 2003 Jan, 97(1), 51 - 8
G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils; Spuck S et al.; In severe pneumonia, the application of granulocyte-colony stimulating factor (G-CSF) was associated with reduced complications possibly by an induction of anti-inflammatory cytokines . It is not clear, whether G-CSF induces interleukin-10 (IL-10) synthesis in neutrophils . In a randomized study, 15 patients with severe community acquired pneumonia were treated either by a single dose of G-CSF and antibiotic therapy (n=8) or antibiotics alone (n=7) . Messenger ribonucleic acid (mRNA) expression of IL-10 and tumor necrosis factor alpha of peripheral blood leukocytes was measured using in-situ hybridization (ISH) and reverse-transcription-polymerase-chain-reaction (RT-PCR) . In addition, the cytokine release of lipopolysaccharide (LPS)-stimulated whole blood was measured by ELISA . We detected increased IL-10 mRNA by ISH (140 +/- 8% vs . -11 +/- 5%, P<0.01) and RT-PCR (126 +/- 16% vs . -28 +/- 3%, P<0.01) in the G-CSF-treated group only . In contrast, LPS-stimulated whole blood cells in vitro released significantly less IL-10 compared to the control group (-38.2 +/- 97 vs . -14.8 +/- 6 pg/ml, P<0.02) . There was no significant effect on IL-10 serum protein levels and the TNF-alpha release and expression . IL-10 mRNA was detected predominantly in cluster designation 66b (CD66b) positive nucleated blood cells indicating that polymorphonuclear leukocytes are the main source of IL-10 expression after G-CSF stimulation . G-CSF induces transcription of IL-10 mRNA in neutrophils without increased release . This may be due to posttranscriptional effects.

Respir Med, 2003 Jan, 97(1), 12 - 9
Improvement of asthma control with a breath-actuated pressurised metred dose inhaler (BAI): a prescribing claims study of 5556 patients using a traditional pressurised metred dose inhaler (MDI) or a breath-actuated device; Price D et al.; A relationship has been reported between sub-optimal inhaler technique and control of asthma symptoms . Randomised controlled trials and systematic reviews may fail to accurately represent this relationship, by excluding patients who are unable to correctly use the reviewed devices . Breath actuated inhalers (BAIs) are reported to be easier to use than metered dose inhalers (MDIs) . This study uses a large primary care medical record database (DIN-LINK) to examine the 'real-life' clinical effectiveness of a BAI vs . traditional MDIs . A comparison is made between the quantity of asthma-related medication (beta2 agonist, oral steroids and antibiotics) and healthcare resource use required by children (0-12 years) and adults (13+ years) using either the BAI or an MDI over a 12-month period . Out of 5556 new asthma patients who met the inclusion criteria, 306 used a BAI and 5250 used a traditional MDI . Children and adults using the BAI received fewer prescriptions for all three medication types than those using a traditional MDI (children: beta2 agonists -18% P=0.036, oral steroids -88% P<0.05, antibiotics -68% P<0.05 and adults: beta2 agonists -10.9% P=0.179, oral steroids -51.2% P<0.05, antibiotics -19.5% P=0.276) . All prescription results reached statistical significance, with the exception of beta2 agonist and antibiotic prescription numbers for adult patients . Children and adults using the BAI required less GP consultations for asthma (children -30.3%, P<0.05 and adults -22.9%, P<0.05) and less GP consultations for respiratory infections than those using a traditional MDI (children -35.2%, P=0.001 and adults -10.4%, P=0.236) . Adults using the BAI required less outpatient appointments than adults using an MDI (-43.7%, P=0.166) . All non-prescription resource results reached statistical significance with the exception of GP consultations for respiratory infections and outpatient visits in the adult group . In conclusion, children and adults using the BAI appear to have better asthma control than children and adults using an MDI as evidenced by fewer relief medication prescriptions and less healthcare resource use.

Wei Sheng Wu Xue Bao, 1999 Dec, 39(6), 546 - 50
{Culture conditions of engineered strain of L-asparaginase and the recombinant plasmid stability}; Wang Y et al.; The growth curves of engineered strain JM105(pASN) were different in LB and M-3 media . The expression level and activity of L-asparaginase were affected apparently by both biomass and induction time . Glucose repression of production of L-asparaginase was found . The stability of the recombinant plasmid pASN in different host strains and in LB and M-3 media was determined . After cultivation inLB broth and M-3 media at 30 degrees C for more than 50 generations without antibiotic selection, then induced at 42 degrees C for up to 5 h, the engineered strains were proved to be stable, except for DHA alpha (pASN).

Dis Aquat Organ, 2002 Dec 10, 52(3), 207 - 15
Host site of activity and cytological effects of histone-like proteins on the parasitic dinoflagellate Amyloodinium ocellatum; Noga EJ et al.; Histone-like proteins (HLPs) are broad-spectrum, endogenously produced antibiotics which we have isolated from tissues of rainbow trout Oncorhynchus mykiss and hybrid striped bass (Morone saxatilis male x M . chrysops female) . Here, we show that HLP-1, which has high sequence homology to histone H2B, equally inhibited both young and mature trophonts of the important ectoparasite Amyloodinium ocellatum . In addition to direct killing of Amyloodinium trophonts, there was evidence that HLP-1 from both rainbow trout and hybrid striped bass caused severe developmental abnormalities, including delayed development, in both the parasitic trophont stage as well as the reproductive tomont stage . The deleterious effects of HLP-1 also were manifested in what appeared to be 'delayed mortality', where parasites of normal appearance would die later in development . Similar serious damage was also seen with calf histone H2B and the unrelated peptide antibiotic magainin 2 . A comparison of the antibiotic activity in mucus versus epidermis compartments of the skin of hybrid striped bass suggested that the majority of antibiotic (including HLP-1) activity resided in the epidermis, although some activity was present in the mucus . These data suggest that normal, nonimmune fish skin contains potent defenses against protozoan ectoparasites and that the effects of these defenses may extend beyond their transient interactions with the parasites, which has important implications for this host-parasite relationship.

Clin Chem Lab Med, 2002 Dec, 40(12), 1334 - 8
C-reactive protein to transthyretin ratio for the early diagnosis and follow-up of postoperative infection; Ferard G et al.; The clinical usefulness of C-reactive protein (CRP) and of transthyretin (TTR) for the early diagnosis and follow-up of infection after an open fracture was prospectively investigated (cohort A) . It was complemented by a retrospective study of trauma patients admitted to an intensive care unit (cohort B) . Serial determinations of serum CRP and TTR concentrations were first performed in uninfected patients from cohort A to define a reference profile during the early postoperative period . It showed a concomitant increase in CRP and decrease in TTR concentrations, followed by progressive return to initial values in patients free from bacterial infection . Variations of the CRP/TTR ratio were analyzed . Recovery phase was defined by an exponential evolution of the two plasma proteins and of their ratio value . The CRP and TTR concentrations were independent of sex and severity of the trauma . In the case of postoperative infection, patients of cohort A revealed amplified CRP and TTR responses usually preceding the occurrence of clinical signs . During successful antibiotic therapy, their recovery response became superimposable to that of the reference group . The same profiles were recorded in cohort B patients admitted with lower limb fractures or various types of trauma . This suggests that observations made on cohort A can be extrapolated to othertrauma patients . We recommend that serial measurements of CRP and TTR and of their ratio should be performed every 2 days to appropriately follow-up these patients.

Pediatr Infect Dis J, 2003 Jan, 22(1), 91 - 2
Simultaneous infection with Borrelia burgdorferi and human granulocytic ehrlichiosis; Moss WJ et al.; A 5-year-old child with simultaneous early Lyme disease and human granulocytic ehrlichiosis (HGE) is described . Because of the shared vector, HGE and Lyme disease are increasingly identified as coinfections in tick-exposed patients . Early recognition of concurrent Lyme disease and HGE is important because amoxicillin, an antibiotic of choice for young children with early Lyme disease, is ineffective for HGE.

Chir Main, 2002 Dec, 21(6), 355 - 8
{Hand replantation in an 88-year-old man: replanted senior?}; Liverneaux P; Indications of hand replantation need to take into account the patient overall condition and assess the magnitude of the injury . Although elderly people are usually considered as a limiting factor for microsurgery, indications of replantation may sometimes be extended . The author reports the case of a complete right hand amputation by a circular saw in an active right-handed 88 year man . The trans-carpal section was clean and general condition of the patient was satisfying . It was decided with the patient consent and the anaesthetist and the surgeon to perform the replantation . The procedure was carried on during 6 hours and revascularization took place 5 h 1/2 after injury . Post-operative period has been easy, but superficial nosocomial wound infection appeared which recovered with antibiotic therapy . It was not necessary to reoperate and the patient did not stay in intensive care department . After almost a 2 years follow-up, peripheral pulses were present, and the hand was warm and well coloured . Poor sensibility was found in median nerve area . Intrinsic motion was missing and extrinsic range of motion was weak . From a functional point of view, the patient was able to write, to dig his garden, and to drive his car . Analysis of this supposed hand replanted senior case report demonstrates that, when general and local conditions are safe, a hand replantation, even with a poor result, may be better than a prosthesis or an allograft, whatever the age of the patient.

JPEN J Parenter Enteral Nutr, 2003 Jan-Feb, 27(1), 52 - 7
Effect of an 8-month treatment with omega-3 fatty acids (eicosapentaenoic and docosahexaenoic) in patients with cystic fibrosis; De Vizia B et al.; BACKGROUND: Supplementation of the diet with eicosapentaenoic acid and docosahexaenoic acid, the main long-chain omega-3 fatty acids in cell membranes, may have beneficial effects in patients with cystic fibrosis . METHODS: A prospective study involving 30 patients and 20 control subjects was carried out; eicosapentaenoic plus docosahexaenoic acid was equal to 1.3% of caloric intake in the cystic fibrosis patients . Our present study included the evaluation of eicosapentaenoic and docosahexaenoic acid incorporation into erythrocyte membranes and biological and clinical effects in response to long-term (8 months) supplementation with fish oil as a source of eicosapentaenoic and docosahexaenoic acids in patients with cystic fibrosis . RESULTS: Baseline erythrocyte membrane fatty acids showed low levels of linoleic acid and eicosapentaenoic acid and mild elevation of 18:3n6, but similar docosahexanoic acid and other fatty acids in cystic fibrosis patients compared with controls . Fish oil supplementation led to a 1.7-fold (p < .05) and 1.3-fold (not significant) increase of eicosapentaenoic acid in erythrocyte membrane phospholipids after 4 and 8 months of supplementation, respectively, and to a 1.67-fold (p < .05) and 1.38-fold (p < .05) increase of docosahexanoic acid, respectively . Along with these changes, there was a progressive decrease of arachidonic acid (from 8.51 to 6.67 g/100 fatty acids at 4 months and 4.83 g/100 fatty acids at 8 months; p < .05) and an increase of linoleic acid (p < .05) in membrane phospholipids . Analysis of inflammatory markers showed a significant decrease of serum immunoglobulin G (IgG) and of alpha-1 antitrypsin (p < .05) concentrations . Pulmonary function testing showed mild but significant improvement of forced expiratory volume (FEV)-1 from 61% +/- 19% to 57% +/- 19% of predicted values (p < .05) . The number of days of antibiotic therapy during the study period was markedly lower compared with the preceding 8-month period (392 versus 721 days; p < .05) . CONCLUSION: Long-term eicosapentaenoic plus docosahexanoic acid supplementation (8 months) has positive effects, such as decreasing inflammation, in cystic fibrosis.

Am J Obstet Gynecol, 2003 Jan, 188(1), 149 - 52
Gentamicin and clindamycin therapy in postpartum endometritis: the efficacy of daily dosing versus dosing every 8 hours; Livingston JC et al.; OBJECTIVE: The objective of the study was to evaluate the efficacy of gentamicin and clindamycin given once daily versus the more common 8-hour dosing regimen for the treatment of postpartum endometritis . STUDY DESIGN: In a prospective, placebo-controlled, double-blinded study, patients who had postpartum endometritis diagnosed were randomly selected to receive 1.5 mg/kg gentamicin and 900 mg clindamycin phosphate administered every 8 hours versus gentamicin 5 mg/kg and clindamycin phosphate 2700 mg administered as a single-daily dose . The single-dose group received an infusion of gentamicin and clindamycin, followed by an administration of intravenous placebo 8 and 16 hours later to maintain blinding . Treatment success was defined as absence of fever 72 hours after initiation of antibiotic therapy . RESULTS: One hundred ten patients were enrolled . The daily-dose group (n = 55) and the thrice-daily dose group (n = 55) were similar with respect to age, gravidity, parity, gestational age, and maternal weight . Clinical characteristics (including maximum temperature, presence of predelivery chorioamnionitis, white blood cell count, and mode of delivery) were also similar . There was no difference in the mean time from initiation of therapy until becoming afebrile in the daily-dose group (27.4 +/- 24.9 hours) compared with the thrice-daily dose group (32.9 +/- 26.3 hours) . Forty-five of 56 (82%) patients in the daily-dose group and 38 of 55 (69%) patients in the thrice-daily dose group had treatment success (P =.12) . CONCLUSION: Once-daily dosing with gentamicin and clindamycin in women with postpartum endometritis has a similar success rate as the standard every 8-hour dosing schedule.

Arch Intern Med, 2003 Jan 27, 163(2), 226 - 30
Outcome and treatment of Bartonella endocarditis; Raoult D et al.; BACKGROUND: Endocarditis caused by Bartonella species is a potentially lethal infection characterized by a subacute evolution and severe valvular lesions . OBJECTIVES: To evaluate the outcome of patients with Bartonella endocarditis and to define the best antibiotic regimen using the following measures: recovery, relapse, or death . METHODS: We performed a retrospective study on 101 patients who were diagnosed in our laboratory as having Bartonella endocarditis between January 1, 1995, and April 30, 2001 . Bartonella infection was diagnosed using immunofluorescence with a 1:800 cutoff, polymerase chain reaction amplification of DNA, and/or culture findings of Bartonella species from whole blood, serum, and/or valvular biopsy specimens . A standardized questionnaire was completed by investigators for each patient . RESULTS: Twelve of the 101 patients died and 2 relapsed . Patients receiving an aminoglycoside were more likely to fully recover (P =.02), and those treated with aminoglycosides for at least 14 days were more likely to survive than those with shorter therapy duration (P =.02) . CONCLUSION: Effective antibiotic therapy for Bartonella endocarditis should include an aminoglycoside prescribed for a minimum of 2 weeks.

J Med Assoc Thai, 2002 Nov, 85(11), 1220 - 5
Ulcerated hemangiomas: clinical features and management; Wananukul S et al.; Hemangioma is the most common tumor of infancy and ulceration is the most frequent complication of hemangioma . The purpose of this report was to review the clinical features and management of ulcerated hemangioma . A retrospective study of ulcerated hemangioma at the outpatient pediatric dermatology clinic, King Chulalongkorn Memorial Hospital from 1992 to 2001 was performed . The medical records of 41 patients were reviewed . Twenty-eight females and 13 males were seen with a female/male ratio of 2.2: 1 . Superficial hemangioma was the most common type (51%) . Head and neck were the most frequently involved sites, affecting 21 cases (51%) . Ulcerated hemangiomas were found on extremities, torso, and perineum of 9 patients (22%), 6 patients (15%) and 5 patients (12%), respectively . Ulceration was developed at a mean age of 3.9 months (range, 1-7 months) . Conventional treatment with topical and/or systemic antibiotic was successfully used in 19 patients (46%) . Oral prednisolone was used in 4 patients with large hemangiomas . The mean duration of treatment with oral prednisolone was 12 months . Flashlamp-pumped pulsed-dye laser (FPDL) was used in 16 patients who failed topical and/or systemic antibiotic . Fifteen patients (94%) healed within 1 to 3 treatments . Excision was done on a small superficial hemangioma on the cheek . In conclusion, head and neck were the most common sites of ulcerated hemangioma . Topical antibiotics and/or systemic antibiotics could be used as the first-line management of ulcerated hemangioma . FPDL was very effective in the treatment of ulcerated hemangioma.

Postgrad Med, 2003 Jan, 113(1), 79 - 82, 85-8, 91-2
The challenge of nonresolving pneumonia . Knowing the norms of radiographic resolution is key; Kyprianou A et al.; Pneumonia that fails to resolve after 10 to 14 days of antibiotic therapy can lead physicians to call for consultation or unnecessary invasive diagnostic procedures . Understanding the infectious and noninfectious causes of pneumonia and their normal times to resolution is enormously helpful in the judicious evaluation of and timely intervention in this very challenging condition.

Spine, 2003 Jan 15, 28(2), 134 - 9
Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion; Silber JS et al.; STUDY DESIGN: This retrospective, questionnaire-based investigation evaluated iliac crest bone graft (ICBG) site morbidity in patients having undergone a single-level anterior cervical discectomy and fusion (ACDF) procedure performed by a single surgeon (T.J.A.) . OBJECTIVE: To evaluate acute and chronic problems associated with anterior ICBG donation, particularly long-term functional outcomes and impairments caused by graft donation . SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion procedures frequently use autologous anterior ICBG to facilitate osseous union . Although autologous ICBG offers several advantages over alternative grafting materials, donor site morbidity can be significant . Acute and chronic complications of donor sites have been reported, yet there are currently no reports of long-term functional outcomes after autologous anterior ICBG donation after single-level ACDF . METHODS: A questionnaire was mailed to 187 consecutive patients who were retrospectively identified to have undergone autologous anterior ICBG harvest for single-level ACDF between 1994 and 1998 . The questionnaire divided items into symptomatic (acute and chronic) and functional assessments . Patients answered yes, no, or not applicable; pain was assessed with a Visual Analogue Scale (VAS) . RESULTS: Surveys were completed either by mail or follow-up telephone interview by 134 patients (71.6%) . Average follow-up was 48 months (range, 24-72 months) . Acute symptoms were reported at the following rates: ambulation difficulty, 50.7%; extended antibiotic usage, 7.5%; persistent drainage, 3.7%; wound dehiscence, 2.2%; and incision and drainage, 1.5% . The chronic symptom questionnaire demonstrated a high degree of satisfaction with the cosmetic result (92.5%) . Pain at the donor site was reported by 26.1% of patients with a mean VAS score of 3.8 in 10, and 11.2% chronically use pain medication . Twenty-one patients (15.7%) reported abnormal sensations at the donor site, but only 5.2% reported discomfort with clothing . A unique functional assessment revealed current impairments at the following rates: ambulation, 12.7%; recreational activities, 11.9%; work activities, 9.7%; activities of daily living, 8.2%; sexual activity, 7.5%; and household chores, 6.7% . CONCLUSIONS: A large percentage of patients report chronic donor site pain after anterior ICBG donation, even when only a single-level ACDF procedure is performed . Moreover, long-term functional impairment can also be significant . Patients should be counseled regarding these potential problems, and alternative sources of graft material should be considered.

J Trauma, 2003 Jan, 54(1), 141 - 4; discussion 144-6
Correlation of intracellular organisms with quantitative endotracheal aspirate; Brasel KJ et al.; BACKGROUND: The presence of intracellular organisms (ICOs) in polymorphonuclear cells obtained from respiratory secretions is a possible method for rapid diagnosis of ventilator-associated pneumonia . We correlated ICOs with quantitative endotracheal aspirate (QA) in intubated patients . METHODS: Consecutive intubated patients in the surgical intensive care unit had respiratory samples obtained every 2 days until extubation . Two thresholds for ICOs and quantitative culture were examined . Sensitivity, specificity, and positive and negative predictive values were calculated using QA as reference . RESULTS: One hundred one samples were obtained from 35 patients . Colony counts >or= 100,000 were found in 34 samples; 60 samples had colony counts >or= 10,000 . Antibiotic use did not affect the sensitivity or specificity of ICOs . Sensitivity of ICOs was 39% to 85%, and specificity was 82% to 97% . Positive predictive value was 70% to 96%, and negative predictive value was 50% to 91% . CONCLUSION: ICOs provide a quick method for establishing the presence of a significant bacterial load in the respiratory tract . Accuracy of ICOs in predicting a positive QA is not affected by concurrent antibiotics.

Ophthal Plast Reconstr Surg, 2003 Jan, 19(1), 75 - 6
Tegaderm transparent dressing (3M) for the treatment of chronic exposure keratopathy; Airiani S et al.; We report an effective alternative treatment of profound chronic exposure keratopathy in a proptotic eye due to intraorbital extension of basal cell carcinoma . The corneal surface gradually reepithelialized in a 6-week period after the first application of Tegaderm transparent dressing (3M, St . Paul, MN, U.S.A.) with instillation of antibiotic ointment on the ocular surface . The patient has been comfortable with an intact epithelial surface, a vascularized cornea, and nonirritated surrounding skin after changing the Tegaderm dressing daily for 15 months . There was no evidence of recurrent corneal ulceration or infiltrations . We conclude that Tegaderm represents a useful treatment of exposure keratopathy due to chronic proptosis.

Pediatr Infect Dis J, 2003 Jan, 22(1), 10 - 6
Impact of the pneumococcal conjugate vaccine on otitis media; Fireman B et al.; CONTEXT: The heptavalent pneumococcal conjugate vaccine (PCV) is recommended for infants to protect against invasive disease, but its impact on otitis might also have public health importance . OBJECTIVE: To examine the impact of PCV on the incidence of otitis media, frequent otitis media and tympanostomy tube procedures and to assess whether the effectiveness of the vaccine wanes after age 24 months and varies by race, sex or season . DESIGN, SETTING AND PATIENTS: From 1995 to 1998, 37 868 children at Kaiser Permanente in Northern California were randomized to receive PCV or a control vaccine in a double blind trial and were followed through April 1999 . INTERVENTIONS: Children received a primary series at 2, 4 and 6 months of age and a booster at 12 to 15 months . MAIN OUTCOME MEASURES: Visits for otitis, frequent visits for otitis and tympanostomy tube procedures . Otitis was ascertained from diagnosis checklists routinely marked by physicians . RESULTS: Control children averaged 1.8 otitis visits per year . Children given PCV had fewer otitis visits than control children in every age group, sex, race and season examined . Intention-to-treat analysis permitted rejection of the null hypothesis that PCV is ineffective against otitis media (P < 0.0001) . In children who completed the primary series per protocol, PCV reduced otitis visits by 7.8% {95% confidence interval (CI), 5.4 to 10.2%} and antibiotic prescriptions by 5.7% (CI 4.2 to 7.2%) . Frequent otitis was reduced by amounts that increased with otitis frequency, from a 10% reduction in the risk of 3 visits to a 26% reduction in the risk of 10 visits within a 6-month period . Tube placements were reduced by 24% (CI 12 to 35%) . CONCLUSION: In children followed up to 3.5 years, PCV provided a moderate amount of protection against ear infections while reducing frequent otitis media and tube procedures by greater amounts.

Am J Med Sci, 2003 Jan, 325(1), 7 - 9
Evaluation and treatment of acute bronchitis at an academic teaching clinic; Hall KK et al.; BACKGROUND: Randomized controlled trials have demonstrated that antibiotics provide no benefit for acute bronchitis, yet 55 to 90% of patients who receive this diagnosis are treated with antibiotics . Given substantial data against antibiotics for acute bronchitis, it could be expected that physicians at academic teaching institutions would be less likely to prescribe antibiotics . However, limited data of antibiotic use for acute bronchitis in this setting has been published . METHODS: Charts of patients seen between January 1 and October 25, 2000, who received an ICD-9 diagnosis of acute bronchitis or upper respiratory infection (URI) at the University of Virginia internal medicine clinic were reviewed . Patients were excluded if they had no cough, chronic obstructive pulmonary disease, symptoms for > or = 3 weeks, or antibiotics for another reason . RESULTS: Of the 160 patients included in this study, 105 (66%) received an antibiotic . Multivariate analysis revealed that patients with increasing age (P = 0.002), purulent cough (P = 0.003), abnormal exam (P = 0.003), and comorbidities (P = 0.03) were most likely to receive an antibiotic . Smoking, duration of symptoms, gender, and race did not predict antibiotic use (P > 0.05) . Macrolides accounted for 68% of antibiotics . Twenty-two (14%) of all patients received a chest radiograph and 72 (45%) received an inhaler . Of those who had chest radiographs negative for signs of infection, 76% received an antibiotic . CONCLUSION: In our teaching clinic, antibiotics were overused, whereas chest radiographs and inhalers were underused for the evaluation and treatment of acute bronchitis . Recently published guidelines will help curb use of antibiotics, but a more intensive intervention, including physician and patient education is probably necessary.

Antimicrob Agents Chemother, 2003 Feb, 47(2), 798 - 9
Conjugative plasmid conferring resistance to olaquindox; Sorensen AH et al.; A conjugative plasmid, pOLA52, conferring resistance to the antibiotic growth promoter olaquindox has been isolated from Escherichia coli from swine manure . It also confers resistance to ampicillin and chloramphenicol and has a high frequency of transfer between strains of E . coli . Plasmid-borne olaquindox resistance has not been demonstrated before.

Vet Immunol Immunopathol, 2003 Jan 30, 91(2), 155 - 60
Cloning of porcine interleukin (IL)-12 receptor beta2 (IL-12Rbeta2) gene and its application to a rapid biological assay for human/porcine IL-12; Kokuho T et al.; Porcine IL-12Rbeta2 gene was cloned from mRNA preparation of mitogen-activated peripheral blood mononuclear cells (PBMCs), and its complete nucleotide sequence was determined . To confirm the biological function, the entire open reading frame (ORF) was re-cloned into a mammalian expression vector, pcDNA3.1/Zeo(+), at the downstream of CMV promoter, and introduced to a Th1-like human lymphoma cell line, Jurkat E6-1 . Antibiotic-resistant cells retaining the expression construct were selected then, isolated by the limiting dilution method . An established clone (10B10) constitutively expressed chimeric IL-12Rs composed of intrinsic (human) beta1 and extrinsic (porcine) beta2 subunits, and produced interferon (IFN)-gamma in response to IL-12 of both species with optimal PHA/PMA stimulation . The production of IFN-gamma was observed as early as 42 h after culture and appeared to be dose-dependent within the range between 20 and 2000 pg/ml . Thus, this clone not only reacts with IL-12 of both species but also provides a useful tool for quick and sensitive detection of IL-12 bioactivity .

Biochim Biophys Acta, 2003 Jan 31, 1609(2), 203 - 10
Beauvericin-induced channels in ventricular myocytes and liposomes; Kouri K et al.; The antibiotic Beauvericin (BEA) was previously shown to express ionophoric properties under simple experimental systems . Its channel-forming activity was examined in inside-out patches of ventricular myocytes and synthetic membranes with the patch clamp and fluorescence imaging techniques . Current transitions to several open state levels were evident after wash-in . The BEA channel is cation-selective . Conductance and kinetics are presented for K(+) and Na(+) substates and main states . The pore was blocked by La(3+) . In myocytes, the {K(+)}(i) was reduced, while {Na(+)}(i) and {Ca(2+)}(i) increased, leading to cytolysis . These results indicate that BEA forms cation-selective channels in lipid membranes, which can affect the ionic homeostasis.

J Paediatr Child Health, 2003 Jan-Feb, 39(1), 55 - 7
School-aged children with Kawasaki disease: high incidence of cervical lymphadenopathy and coronary artery involvement; Fan PC et al.; OBJECTIVE: We describe 10 school-aged children with Kawasaki disease (KD) with a high incidence of cervical lymphadenopathy and coronary abnormality . METHODS: Based on a database of 1002 children with KD in Chang Gung Children's Hospital from January 1983 to March 2001, 10 (1%) school-aged patients (five boys, five girls) who met the diagnostic criteria of KD were included for analysis . RESULTS: Cervical lymphadenopathy was noted in all (100%) of these patients . Unilateral neck mass mimicking acute suppurative infections not responding to antibiotic therapy was the initial presentation in nine (90%) of the 10 patients . The mean interval between disease onset and diagnosis was 9.9 +/- 3.3 days (range, 6-15 days) . Seven (70%) of these patients responded to one course of high-dose intravenous immunoglobulin (IVIG) therapy (2 g/kg) and oral aspirin (80-100 mg/kg per day), two (20%) required a second course of IVIG, and one (10%) responded to high-dose aspirin treatment only . Coronary artery abnormality (dilatation or aneurysm) was documented by echocardiography in seven (70%) patients (four boys, three girls) . In six patients, the coronary artery abnormalities resolved in 1 year, while one patient had persistent right coronary artery aneurysm, which necessitated continued anticoagulant and low-dose aspirin therapy . CONCLUSION: The incidence of school-aged children among patients with KD is about 1% in our hospital . These patients are notable for the high incidence of initial manifestations of unilateral neck mass and coronary artery involvement . This disease should be listed as the differential diagnosis in school-aged children presenting with fever and neck mass that do not respond to antibiotic therapy.

J Nat Prod, 2003 Jan, 66(1), 62 - 6
Metabolites of a blocked chloramphenicol producer; Lewis EA et al.; Addition of p-aminophenylalanine (4), an advanced biosynthetic precursor of the antibiotic chloramphenicol (5), to a Streptomyces venezuelae pabAB mutant (VS629) restored chloramphenicol production and led to formation of the non-chlorinated analogue corynecin II (6) and four acetanilide derivatives: p-(acetylamino)phenylalanine (7), p-(acetylamino)benzyl alcohol (13), p-(acetylamino)benzoic acid (14), and p-(acetylamino)phenol (acetaminophen, 16) . Metabolite structures were deduced from NMR and MS-MS data and established by chromatographic and spectroscopic comparisons with authentic samples . Reference compound 13 was synthesized by reducing the acid chloride of 14 . Shunt pathways are proposed to account for the formation of the metabolites from p-aminophenylalanine.

Hamostaseologie, 2002 Dec, 22(4), 149 - 53
{Treatment of superficial thrombophlebitis}; Raake W et al.; Superficial thrombophlebitis is a frequently occurring disease which, because of risk factors, affects women to a greater extent than men . The presence of deep venous thrombosis should be excluded by imaging procedures . Heparin or low-molecular weight heparins are indicated for treatment, if deep venous thrombosis is present or threatening . In the acute stage non-steroidal antiinflammatory drugs can be taken orally in order to alleviate pain and inflammation . In the case of concomitant chronic venous insufficiency, edema protective drugs (e . g . preparations containing horse chestnut extract and flavonoids) can support the therapy . For the treatment of inflammatory conditions in relatively short superficial vein segments without involvement of the deep venous system, a limitation to topical treatment is possible . In addition to compression therapy, the application of creams or gels containing heparin or heparinoids are the usual treatment approach . The use of topical products containing mucopolysaccharide polysulfate (MPS) has been proven to be beneficial . The problem of providing evidence of the efficacy of topical products in the therapy for superficial thrombophlebitis under the current strict demands of our regulatory authorities and of developing new products under these conditions is discussed.

Infect Immun, 2003 Feb, 71(2), 671 - 5
Restoration of cytoadherence to an adherence-deficient mutant of Mycoplasma arthritidis by genetic complementation; Washburn LR et al.; Mycoplasma arthritidis causes a severe septic arthritis in rats under natural and experimental conditions . An earlier study implicated a membrane lipoprotein designated MAA1 in cytadherence of M . arthritidis . In addition, a spontaneous adherence-deficient mutant was shown to contain a nonsense mutation in the gene encoding MAA1, resulting in production of a truncated product, MAA1Delta . In the present study, a wild-type maa1 gene carried on transposon Tn4001T was introduced into the low-adherence mutant by polyethylene glycol-mediated transformation . The presence of the tranposon and the wild-type maa1 gene in the chromosome of transformants was confirmed by PCR and Southern hybridization . The latter procedure also confirmed that each transformant contained a single copy of the transposon . Western immunoblotting showed that transformants produced both wild-type MAA1 and MAA1Delta, indicating that the introduced wild-type maa1 gene was functional . This phenotype was stably maintained after multiple subcultures even in the absence of antibiotic selection . Finally, transformants were shown to adhere to rat L-2 lung cells in culture at wild-type levels, providing confirmation for an important role for MAA1 in adherence.

Adv Ther, 2002 Sep-Oct, 19(5), 229 - 42
IV-to-oral switch therapy for community-acquired pneumonia requiring hospitalization: focus on gatifloxacin; Pelly L; The majority of the 1.1 million patients hospitalized for community-acquired pneumonia (CAP) in the United States begin therapy with an intravenous antibiotic . A switch to oral therapy as soon as patients are clinically stable reduces the length of hospitalization and associated costs . Fluoroquinolones are appropriate candidates for switch therapy . Gatifloxacin is an excellent choice when a fluoroquinolone is being considered for sequential switch therapy in the treatment of CAP requiring hospitalization.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2000 Aug, 18(4), 215 - 8
{Histological study on the polyhydroxybutyric ester(PHB) membrane used for guided bone regeneration around titanium dental implants}; Ou G et al.; OBJECTIVE: To evaluate the effects of PHB membrane around dental titanium implants used in guided bone regeneration technique . METHODS: Endosseous cylindrical implants were placed in dogs' mandibles after extraction of all the mandibular premolars and the first molars immediately . Ideal implant placement sites were modified by creating standardized 3 mm x 5 mm facial dehiscent defects . The defects were covered with PHB membrane and titanium membrane respectively, then the membranes were fixed on the periosteum by sutures, and the remainder served as controls . Tissue closure was achieved with mattress and interrupted single sutures, and antibiotic injection was given to the dogs in the following 3 days . The dogs were divided into three groups according to the healing time of 1, 2 and 3 months, then the three groups of dogs were sacrificed . After that, tissue blocks containing the implants and the control ones were removed and studied by gross observation, X-ray radiograph and fluorescence microscope, and the surfaces of the membranes were observed by scanning electron microscope . The specimen used for light microscope study were fixed with 10% formaldehyde for 24 hours, and decalcified with 0.5 mol/L EDTA for 2 weeks . After the titanium implants were carefully removed, the tissue blocks were embedded into the paraffin wax, and the sections were obtained . RESULTS: The PHB membrane degraded slowly and partly 3 months after placement, and the biodegradable property of the PHB membrane deserved a longer period of study; The bone defects covered with PHB and titanium membrane were filled with much more new bone than that of the control group . CONCLUSION: PHB membrane can enhance bone formation and can be used for guided bone regeneration.

Hua Xi Kou Qiang Yi Xue Za Zhi, 2000 Feb, 18(1), 20 - 2, 33
{A study of polysaccharide-protein complex and glycosyls in the tissue surrounding titanium implant of rabbit}; Bai W et al.; OBJECTIVE: The absorption of the polysaccharide-protein complex to the implant surface may be the first reaction between the implant and the surrounding tissue . So we observed the distribution and the relative amount of the polysaccharide-protein complex and glycosyls in order to find out the possible functions and changing rules of these substances . METHODS: 12 rabbits were selected according to the age, sex, weight, and health conditions . Bilateral mandibular premolar teeth of rabbits were extracted under abdomen anesthesia (2% glutababituratic acid), then 12 titanium implants were placed into the teeth extraction holes of one side and left the other side to be the control one . All of the implants were required to be placed 2 mm below the alveolar crest, and tissue closure was achieved with mattress and interrupted single sutures . Antibiotic injections were given to the rabbits in the following 3 days . The animals were sacrificed at the end of 1 week, 4 weeks and 24 weeks . Tissue blocks (4 mm x 4 mm x 4 mm) containing the titanium implants and the control ones were removed, then fixed with 10% formaldehyde for 2 weeks, and decalcified with 10% EDTA (pH7.0) for 8 weeks . Carefully removed the titanium implants, the tissue blocks were embedded into the paraffin wax, then the sections were obtained and stained using following methods . 1 . Alcian Blue Method: Alcian blue (pH 2.5) staining displayed the acidic proteoglycans; Alcian blue (pH 1.0) displayed the proteoglycans containing sulfonyl; Alcian blue/periodix acid-shiff staining demonstrated the acidic and neutral proteoglycans respectively . Alcian blue-MgCl2 with different ionic concentration identified the different kinds of proteoglycans . 2 . Lectin Method: 5 kinds of lectins were used to locate 5 kinds of glycosyls . 2.5 micrograms/ml ConA located the glucose; 10 micrograms/ml PNA located the galactose; 10 micrograms/ml WGA located the N-acetylglucosamine; 25 micrograms/ml PHA-E located N-acetylgalactosamine, 10 micrograms/ml WPL loacted the fucose . RESULTS: High level of proteoglycans and glycosyls were observed in the peri-implant connective tissue during all phases of the experiment . It was also observed that polysaccharide-protein complex and glycosyls reached a high level in new bone matrix as well as osteoblasts . CONCLUSION: Polysaccharide-protein complex and glycosyls do play an important role in the implant-bone attachment, and titanium compatibility and may be closely related to the bone metabolic activity.

Clin Infect Dis, 2003 Feb 1, 36(3), e35 - 9 Epub 2003 Jan 17.
Bradycardic syncope in 2 patients who recently began gatifloxacin treatment; Nicholson WJ et al.; Gatifloxacin is a synthetic broad-spectrum 8-methoxyfluoroquinolone approved by the United States Food and Drug Administration in December 1999 . Few side effects of this new antibiotic have been reported, and there are no previous case reports of bradyarrhythmias . We report 2 cases of syncope due to bradycardia in patients who recently began treatment with gatifloxacin.

J Thorac Cardiovasc Surg, 2003 Jan, 125(1), 79 - 83; discussion 83-4
Primary thoracoscopic treatment of empyema in children; Cohen G et al.; OBJECTIVE: The optimal treatment of pediatric empyema remains controversial . The objective of this study is to compare the use of conventional management versus primary thoracoscopic drainage and decortication in children with empyema . METHODS: Conventional management has consisted of chest drain insertion under general anesthesia plus intravenous antibiotics . Thoracoscopic drainage and decortication has consisted of primary thoracoscopic drainage and decortication plus antibiotics . The clinical course of 54 patients treated conventionally between 1989 and 1997 was compared with that of 21 patients treated by means of thoracoscopic drainage and decortication between September 2000 and September 2001 . RESULTS: Results of the study demonstrated that patients in the drainage-decortication group had fewer invasive interventions per patient than those in the conventional management group (1.0 vs 1.26) . Patients undergoing thoracoscopic drainage and decortication also had significantly shorter durations of intravenous antibiotic therapy (7.6 +/- 1.2 vs 18.2 +/- 7.5 days), chest tube drainage (4.0 +/- 0.5 vs 10.2 +/- 6.1 days), and hospital stays (7.4 +/- 0.8 vs 15.4 +/- 7.4) . Moreover, there were no open thoracotomies and decortications in the thoracoscopic drainage and decortication group, whereas in the conventional management group 39% (21/54) of patients underwent an open procedure . CONCLUSION: Although the 2 groups were not prospectively randomized and they were treated in different time periods, the results of this study support the use of thoracoscopic surgery as the primary therapeutic modality in children presenting with pleural empyema . This strategy appears to offer significant benefits over conventional treatment in terms of duration of treatment and the need for more invasive surgery.

J Agric Food Chem, 2003 Jan 29, 51(3), 587 - 93
Neamin as an immunogen for the development of a generic ELISA detecting gentamicin, kanamycin, and neomycin in milk; Loomans EE et al.; A broad-specific ELISA using one antibody preparation for the detection of gentamicin, kanamycin, and neomycin in milk is reported for the first time . For the immunization of rabbits, neamin was used as the generic hapten on the basis of the facts that it is a two-ring fragment of neomycin and, in shape and charge, it resembles parts of kanamycin and gentamicin . Neamin was linked to the preactivated carrier protein keyhole limpet hemocyanin by EDC coupling . The specificity and sensitivity of the polyclonal antibodies for the aminoglycoside antibiotics were tested in a competitive assay using homologous and heterologous conjugates coupled by various conjugation procedures as the ELISA solid phase . In contrast to the homologous assay recognizing only neomycin, the heterologous assay could be used for the detection of the whole subclass of deoxystreptamin antibiotics in buffer and raw milk . Gentamicin, kanamycin, and neomcyin were detected in artificially contaminated undiluted raw milk (without sample pretreatment) with 50% inhibition levels at 9, 21, and 113 ng mL(-)(1), respectively . Neomycin levels were also measured in milk samples obtained from a cow suffering from mastitis and treated with an antibiotic cocktail including neomycin . Levels below the EU maximum residue levels for deoxystreptamin antibiotics could readily be measured in this generic ELISA.

World J Gastroenterol, 2003 Feb, 9(2), 309 - 11
Evaluation of the string test for the detection of Helicobacter pylori; Leong RW et al.; AIM: Helicobacter pylori can be diagnosed by invasive or non-invasive tests but to obtain bacteria for culture and antibiotic susceptibility testing, an upper GI endoscopy is often required . The string test may be a minimally-invasive alternative method of obtaining H . pylori samples . This study evaluates the sensitivity and specificity of the string test in the diagnosis of H . pylori in comparison with endoscopic means of diagnosis . METHODS: This was a prospective open comparative study of patients with dyspepsia with endoscopy-based tests as gold standard (defined as a positive CLO test and antral histology) . Fasting patients swallowed the encapsulated-string (Entero-test Hp), which was withdrawn after 1 hour . The gastric juice from the string was plated onto H . pylori-selective media for culture . Helicobacter pylori was identified by typical colony morphology, gram stain and biochemical test results . RESULTS: Thirty dyspeptic patients were recruited of whom 21 (70 %) were positive for H . pylori according to the gold standard . The sensitivity, specificity, positive predictive value, and negative predictive value for the string test were 38 %, 100 %, 100 % and 41 % respectively, and for endoscopic biopsies 81 %, 100 %, 100 %, 69 % respectively (P=0.004) . Logistic regression showed that only abundant growth density from endoscopic biopsy cultures to be a predictor of a positive string test (P=0.018) . CONCLUSION: The string test is an alternative method to endoscopy in obtaining H . pylori but has a low sensitivity compared to endoscopic biopsies.

Ugeskr Laeger, 2002 Dec 30, 165(1), 51 - 2
{Spondylodiscitis as a complication to ultrasound-guided transrectal prostatic biopsy}; Koefoed-Nielsen J et al.; We report a case of spondylodiscitis and psoas abscess induced by transrectal ultrasound-guided prostatic biopsy in a 70-year-old man . Multi-resistant E . coli was cultured, and the patient was cured after several trials with antibiotic treatments.

Ann Intern Med, 2003 Jan 21, 138(2), 109 - 18
Testing strategies in the initial management of patients with community-acquired pneumonia; Metlay JP et al.; The initial management of patients suspected of having community-acquired pneumonia is challenging because of the broad range of clinical presentations, potential life-threatening nature of the illness, and associated high costs of care . The initial testing strategies should accurately establish a diagnosis and prognosis in order to determine the optimal treatment strategy . The diagnosis is important in determining the need for antibiotic therapy, and the prognosis is important in determining the site of care . This paper reviews the test characteristics of the history, physical examination, and laboratory findings, individually and in combination, in diagnosing community-acquired pneumonia and predicting short-term risk for death from the infection . In addition, we consider the implications of these test characteristics from the perspective of decision thresholds . The history and physical examination cannot provide a high level of certainty in the diagnosis of community-acquired pneumonia, but the absence of vital sign abnormalities substantially reduces the probability of the infection . Chest radiography is considered the gold standard for pneumonia diagnosis; however, we do not know its sensitivity and specificity, and we have limited data on the costs of false-positive and false-negative results . In the absence of empirical evidence, the decision to order a chest radiograph needs to rely on expert opinion in seeking strategies to optimize the balance between harms and benefits . Once community-acquired pneumonia is diagnosed, a combination of history, physical examination, and laboratory items can help estimate the short-term risk for death and, along with the patient's psychosocial characteristics, determine the appropriate site of treatment.

Br J Plast Surg, 2002 Oct, 55(7), 561 - 4
Paediatric transcranial surgery: a review of 114 consecutive procedures; Kirkpatrick WN et al.; Craniofacial units have a responsibility to collect data, to promote research and training and to carry out audit . We present a review of 114 consecutive transcranial procedures performed in 110 children in our unit over an 8 year period, with particular reference to complications . There were no deaths in this series . Complications included two cases of excessive intraoperative blood loss necessitating a delay in the procedure, and two postoperative infections that required aggressive antibiotic management . Minor complications, delaying hospital discharge, occurred in 13 patients . Within the range of paediatric transcranial procedures performed, the potential for complications is greater for complex osteotomies in syndromic conditions than for single sutural synostosis correction . The transcranial case mix included a relatively small number of craniofacial dysostoses, which contributes to the very low complication rate reported . This report demonstrates that multidisciplinary assessment and planning, adherence to craniofacial surgical principles, shorter operating times and avoidance of high-risk procedures contribute to a low complication rate, and confirms that paediatric transcranial procedures can be safely performed in dedicated centres where there is a multidisciplinary team with appropriate commitment and experience.

Hua Xi Yi Ke Da Xue Xue Bao, 2001 Dec, 32(4), 596 - 8, 626
{Mitochondrial DNA mutations in matrilineal nonsyndromic deafness pedigrees of southwest China}; Zhang N et al.; OBJECTIVE: To identify the incidence of the 1555A-->G mutation and explore the audiological features of pedigrees with matrilineal non-syndromic deafness in Southwest of China so as to provide the theoretical evidence for establishing the method of gene diagnosis . METHODS: Six pedigrees with 102 members were evaluated audiologically and clinically . DNA was extracted from their blood samples . All subjects were screened for mitochondrial DNA 1555A-->G mutation by Alw 26I restriction endonuclease digestion . RESULTS: Seventeen maternal relatives of aminoglycoside antibiotic induced deafness (AAID) pedigree 1 and pedigree 2, carried 1555A-->G mutation . 10 maternal relatives of Non-AAID pedigree 6 also carried 1555A-->G mutation . No mutation was found among paternal relatives and pedigrees 3, 4 and 5 . CONCLUSION: The same audiological features of these pedigrees are: bilateral and symmetrical progressive sensorineural hearing loss with variable age of onset . The 1555A-->G mitochondrial mutation is one of the hereditary factors for this disorder . 4 Aminoglycoside antibiotic plays an important role in developing deafness . The incidence of the 1555A-->G mutation in AAID and matrilineal non-syndromic deafness pedigrees is fairly high . Screening for mitochondrial 1555A-->G mutation may be of great clinical use fullness.

Biomaterials, 2003 Apr, 24(8), 1459 - 68
Interpolymer complexes of poly(acrylic acid) and chitosan: influence of the ionic hydrogel-forming medium; de la Torre PM et al.; Non-covalent polyionic complexes were developed for localized antibiotic delivery in the stomach . Freeze-dried interpolymer complexes based on polyacrylic acid (PAA) and chitosan (CS) were prepared in a wide range of copolymer compositions by dissolving both polymers in acidic conditions . The influence of hydrogel-forming medium on the swelling and drug release was evaluated . The properties of these complexes were investigated by using scanning electron microscopy, dynamic swelling/eroding and release experiments in enzyme-free simulated gastric fluid (SGF) . The electrostatic polymer/polymer interactions generate polyionic complexes with different porous structures . In a low pH environment, the separation of both polymer chains augmented as the amount of cationic and carboxilic groups increased within the network . However, the presence of higher amount of ions in the hydrogel-forming medium produced a network collapse, decreasing the maximum swelling ratio in SGF . PAA:CS:A (1:2.5:2)-1.75 M complexes released around 54% and 71% of the amoxicillin in 1 and 2 h, respectively, in acidic conditions . A faster drug release from this interpolymer complex was observed when the ionic strength of the hydrogel-forming medium increased . Complexes with a high amount of both polymer chains within the network, PAA:CS:A(2.5:5:2), showed a suitable amoxicillin release without being affected by an increased amount of ions in the hydrogel-forming medium . These freeze-dried interpolymer complexes could serve as potential candidates for amoxicillin delivery in an acidic enviroment .

Int J Pharm, 2003 Jan 16, 250(2), 403 - 14
Efficacies of cyclodextrin-complexed and liposome-encapsulated clarithromycin against Mycobacterium avium complex infection in human macrophages; Salem II et al.; Cyclodextrins and liposomes have been used in recent years as drug delivery vehicles, improving the bioavailability and therapeutic efficacy of many poorly water-soluble drugs . In this study, we used two approaches to enhance the availability of the poorly water-soluble antibiotic, clarithromycin, by inclusion complex formation and by liposome-encapsulation . We examined the efficacies of these formulations against Mycobacterium avium complex (MAC) in human peripheral blood monocyte-derived macrophages . The water solubility of clarithromycin was enhanced by about 700-fold by complexation with cyclodextrin . The use of a rapid radiometric (BACTEC) method for the detection of MAC growth and susceptibility showed identical MICs against MAC for both the free and complexed drug . The anti-MAC efficacy of the cyclodextrin complex of clarithromycin in macrophages was slightly lower than the free drug, probably due to the high stability of the inclusion complex . At higher drug concentrations, Liposome-encapsulated clarithromycin was slightly more effective against intracellular MAC growth than the free drug.

Rev Gastroenterol Peru, 2002 Oct-Dec, 22(4), 287 - 96
{Comparative evaluation of the surgical treatment of acute appendicitis: open appendicetomy versus laparoscopic appendicectomy in the national hospital hospital Carlos a . Seguin e . Essalud}; Rivera Diaz EM; STATE OF THE PROBLEM: To establish the advantages and disadvantages of open appendicectomy versus laparoscopic appendicectomy in the surgical treatment of acute appendicitis in the National Hospital Carlos Alberto Seguin Escobedo . OBJECTIVES/AIMS: Comparative evaluation of open appendicectomy versus laparoscopic appendicectomy in their grouped in: a) Characters/Features.- Age, sex, occupation, time of disease, symptoms and signs, laboratory investigations, pre and post operative diagnoses, pre and post operative antibiotic therapy and time of anesthesia, b) Impact of surgical techniques in: preoperative time, operative time, operative accidents, stay in hospital and postoperative complications, and c) Evaluation of the benefits through comparative costs of both techniques . Survey Material . It was made/done a comparative survey of 100 cases/events of open Apendicectomy versus 100 cases/events of Laparoscopic Appendicectomy . RESULTS: In the comparative evaluation of both surgical techniques there is not significant difference in: age, time of disease, time of waiting before the operation, stay in hospital, postoperative complications . There are significant difference in: sex, more frequency in female in laparoscopic appendicectomy; general anesthesia more frequent in laparoscopic appendicectomy; longer operative time in laparoscopic appendicectomy (103.03 min); higher total cost on average in laparoscopic appendicectomy (2047.97 new soles) conversion index laparoscopic appendicectomy 4% CONCLUSION: Laparoscopic appendicectomy does not offer significant benefits over open appendicectomy in patients with acute appendicitis with the exception of the esthetic aspect in women and disadvantages langer operative time and more expensive.

Gene Ther, 2003 Jan, 10(1), 84 - 94
Tetracycline-inducible transgene expression mediated by a single AAV vector; Chtarto A et al.; Regulated gene delivery systems are usually made of two elements: an inducible promoter and a transactivator . In order to optimize gene delivery and regulation, a single viral vector ensuring adequate stoichiometry of the two elements is required . However, efficient regulation is hampered by interferences between the inducible promoter and (i) the promoter used to express the transactivator and/or (ii) promoter/enhancer elements present in the viral vector backbone . We describe a single AAV vector in which transcription of both the reverse tetracycline transactivator (rtTA) and the transgene is initiated from a bidirectional tetracycline-responsive promoter and terminated at bidirectional SV40 polyadenylation sites flanking both ITRs . Up to 50-fold induction of gene expression in human tumor cell lines and 100-fold in primary cultures of rat Schwann cells was demonstrated . In addition an 80-fold induction in vivo in the rat brain has been obtained . In vitro, the autoregulatory vector exhibits an induced expression level superior to that obtained using the constitutive CMV promoter . Although extinction of the transgene after removal of tetracycline was rapid (less than 3 days), inducibility after addition of tetracycline was slow (about 14 days) . This kinetics is suitable for therapeutic gene expression in slowly progressive diseases while allowing rapid switch-off in case of undesirable effects . As compared to previously described autoregulatory tet-repressible (tetOFF) AAV vectors, the tet-inducible (tetON) vector prevents chronic antibiotic administration in the uninduced state.

Curr Infect Dis Rep, 2003 Feb, 5(1), 66 - 73
Emerging Causes of Traveler's Diarrhea: Cryptosporidium, Cyclospora, Isospora, and Microsporidia; Goodgame R; Travel is a risk factor for acquiring infection with a spore-forming protozoa: Cryptosopridium, Cyclospora, Microsporidia, and Isospora . Certain travel destinations have a high disease burden and intense exposure . Patients present with persistent diarrhea and a history of recent travel to a developing country in the tropics . Very mild infections may be underdiagnosed and may cause typical traveler's diarrhea . In a patient with a history of travel and persistent diarrhea unresponsive to the usual antibiotic and antidiarrhea treatment, stool studies for all four of these protozoa infections should be performed . If immune status is normal and the disease is mild, symptomatic therapy may suffice . Effective treatment is available for Cyclospora, Microsporidia, and Isospora.

Pharmacotherapy, 2003 Jan, 23(1), 101 - 3
Neutropenia after single-dose clindamycin for dental prophylaxis; Bubalo JS et al.; A 68-year-old man with stable chronic myelogenous leukemia received a single dose of clindamycin before having a tooth extracted . He was neutropenic 6 days later, with an absolute neutrophil count of 945 cells/mm3 . His neutrophil count returned to normal within 2 weeks . Clindamycin has been implicated in drug-induced neutropenia; however, a review of the literature produced only three reports of this reaction . Only one provided the duration of the neutropenia . To our knowledge, this case report is only the second that provides the duration of the clindamycin-induced neutropenia . Clinicians should be made aware of this potential adverse event.

Ann Acad Med Singapore, 2002 Nov, 31(6), 756 - 60
Aseptic meningitis in children--the Singapore experience; Tee WS et al.; OBJECTIVE: To study the incidence, aetiology, clinical characteristics and management of paediatric aseptic meningitis in a paediatric hospital in Singapore . MATERIALS AND METHODS: Patients with cerebrospinal fluid (CSF) pleocytosis, a negative Gram stain and bacterial culture were reviewed retrospectively from 1 January to 31 December 2000 . Eighty-seven patients who fulfilled the criteria for aseptic meningitis and without neurological deficits were studied . In addition, reverse transcriptase polymerase chain reaction (RT-PCR) using pan enterovirus primers was subsequently performed on 73 of these CSF specimens which were available for storage . RESULTS: The incidence of aseptic meningitis was approximately 37 cases per 10,000 admissions . Non-polio enteroviruses were isolated from 29 of 64 (45.3%) CSF and 38 of 52 (73.1%) stool samples . RT-PCR was positive in 43 (58.9%) of the archived CSF specimens . The aetiologies of the remaining cases were mostly unidentified . Their ages ranged from 5 days to 12 years (median, 2 months) . All patients except 1 had fever . Vomiting or poor feeding occurred in 44.7%, cough or running nose in 35.3%, irritability was observed in 35.3%, seizures in 7.1%, a rash in 10.6% and diarrhoea in 5.9% . All patients recovered without sequelae . The median CSF white cell count was 212 cells/mm3 (range, 7 to 12,000) . The median glucose concentration was 2.7 mmol/L (range, 1.6 to 4.4) . The median CSF/blood glucose ratio was 0.52 (range, 0.23 to 0.73) . Median length of stay was 7 days (range, 4 to 17) . Eighty-four patients (96.6%) received antibiotics for a median of 5.5 days (range, 2 to 14) . CONCLUSION: Enteroviruses were the most common aetiologic agent identified . A method of early diagnosis using RT-PCR for enteroviruses is necessary to reduce the current duration of antibiotic usage and to decrease the length of hospital stay.

Cochrane Database Syst Rev . 2002;(4):CD002033.
Nystatin prophylaxis and treatment in severely immunodepressed patients; Gotzsche PC et al.; BACKGROUND: Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although the effect seems to be equivocal . OBJECTIVES: To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency . SEARCH STRATEGY: MEDLINE and The Cochrane Library using a comprehensive search strategy, date of last search November 2001 . Contacted industry and scanned reference lists . SELECTION CRITERIA: Randomised trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B . DATA COLLECTION AND ANALYSIS: Data on mortality, invasive fungal infection and colonisation were extracted by both authors independently . A random effects model was used unless p>0.10 for the test of heterogeneity . MAIN RESULTS: We included 12 trials (1,464 patients) . The drugs were given prophylactically in ten trials and as treatment in two . Seven trials were in acute leukaemia, two in cancer, one in liver transplant patients, one in critically ill surgical and trauma patients, and one in AIDS patients . Nystatin had been compared with placebo in three trials and with fluconazole in nine; the dose varied from 1.5 MIE to 72 MIE daily . The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk 0.85, 95% confidence interval 0.65 to 1.13) . There was no statistically significant difference between fluconazole and nystatin on mortality (relative risk 0.76, 0.49 to 1.18) whereas fluconazole was more effective in preventing invasive fungal infection (relative risk 0.37, 0.15 to 0.91) and colonisation (relative risk 0.49, 0.34 to 0.70) . The results were very similar if the three studies which were not performed in cancer patients were excluded . REVIEWER'S CONCLUSIONS: Nystatin cannot be recommended for prophylaxis or treatment of Candida infections in immunodepressed patients.

Cochrane Database Syst Rev . 2002;(4):CD001935.
Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children; Butler CC et al.; BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss with associated developmental delay . Treatment remains controversial . The effectiveness of both systemic and topical intranasal steroids in promoting the resolution of effusions has been assessed by randomised controlled trials . OBJECTIVES: To examine evidence for or against treating children with hearing loss associated with OME with systemic or topical intranasal steroids . SEARCH STRATEGY: Searches were conducted in January 2002 . We searched the Cochrane Controlled Trials Register using the terms 'otitis media', 'otitis media with effusion', 'glue ear', or 'OME', and 'steroids', 'glucocorticoids, synthetic', 'glucocorticoids, topical', 'anti-inflammatory agents, steroidal' . EMBASE and MEDLINE were also searched for additional information . SELECTION CRITERIA: Randomised controlled trials of oral and topical intranasal steroids, either alone or in combination with another agent such as an antibiotic, were included . Exclusions: publications in abstract form only since adequate appraisal was not possible; uncontrolled, non-randomised or retrospective studies; studies reporting outcomes with ears (rather than children) as the unit of analysis unless data were of sufficient detail to allow analysis by child . DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports by the two authors independently (CCB and JH van der V) using standardised data extraction forms and methods . The methodological quality of the included studies was independently assessed by the two authors using the scheme described in the Cochrane Handbook . Dichotomous results were expressed as an odds ratio using a fixed effects model together with the 95% confidence intervals . Continuous data were analysed using the weighted mean difference in a fixed effects model . Tests for heterogeneity between studies were performed using a Mantel-Haenszel approach . In trials with a cross over design, post crossover treatment data were not used . MAIN RESULTS: No study prospectively documented hearing loss associated with OME prior to randomisation . Follow up was mainly short term . No serious or lasting adverse effects were reported in the six studies that did mention adverse effects . Most comparisons involved small numbers of subjects . The odds ratio for OME persisting after short term follow up in children treated with oral steroids compared to control was 0.22 (95% CI 0.08 to 0.63) . The odds ratio for OME persisting after short term follow up for children treated with oral steroids plus antibiotic compared to control plus antibiotic was 0.32 (95% CI 0.20 to 0.52) . However there was significant heterogeneity between studies included in the latter comparison (p<0.01) . Trends favoured steroids for most other comparisons, but confidence intervals included unity . There was no evidence of benefit for steroid treatment for resolution of OME or of resolution of hearing loss associated with OME in the longer term . REVIEWER'S CONCLUSIONS: Both oral and topical intranasal steroids alone or in combination with an antibiotic lead to a quicker resolution of OME in the short term . However, there is no evidence of a long term benefit from treating OME effusions or associated hearing loss with either oral or topical intranasal steroids . No serious adverse events were reported in the six studies that presented data on adverse effects . Future studies should document hearing loss associated with OME before the start of study treatment . Follow up should be longer and ideally include health related quality of life and hearing assessments . Data should not be presented only with ears as the unit of analysis.

Acta Obstet Gynecol Scand, 2002 Dec, 81(12), 1132 - 8
Comparative study of vaginal, laparoscopically assisted vaginal and abdominal hysterectomies for uterine myoma larger than 6 cm in diameter or uterus weighing at least 450 g: a prospective randomized study; Hwang JL et al.; BACKGROUND: The purpose of this study was to compare peri-operative morbidity, preoperative sonographic estimation of uterine weight and postoperative outcomes of women with uterine fibroids larger than 6 cm in diameter or uteri estimated to weigh at least 450 g, undergoing either vaginal, laparoscopically assisted vaginal or abdominal hysterectomies . METHOD: Ninety patients who met the criteria of uterine fibroids larger than 6 cm by ultrasonographic examination were included in our prospective study . Patients were randomized into laparoscopic-assisted vaginal hysterectomy (30 patients), vaginal hysterectomy (30 patients) and abdominal hysterectomy (30 patients) groups . RESULTS: The laparoscopically assisted vaginal hysterectomy group had significantly longer operative times than the abdominal and vaginal hysterectomy groups (109 +/- 22 min, 98 +/- 16 min, and 74 +/- 22 min, respectively, p < 0.001) . Blood loss for vaginal hysterectomy was significantly lower than for either abdominal or laparoscopically assisted vaginal hysterectomies (215 +/- 134 ml, 293 +/- 182 ml, and 343 +/- 218 ml, respectively, p = 0.04) . Vaginal hysterectomy and laparoscopically assisted vaginal hysterectomy groups had shorter hospital stays, lower postoperative pain scores, more rapid bowel recovery and lower postoperative antibiotic use than the abdominal hysterectomy group . Uterine weight in the abdominal hysterectomy group was significantly heavier than in the vaginal and laparoscopically assisted vaginal hysterectomy groups (1020 +/- 383 g, 835 +/- 330 g, and 748 +/- 255 g, respectively, p = 0.02) . We estimated that when a myoma measured between 8 and 10 cm, the uterus weighed approximately 450 g, and the sensitivity of this prediction was 57.5% . For a myoma larger than 13 cm, the estimated uterine weight was more than 900 g and the sensitivity of this prediction was 71% . CONCLUSION: The study shows vaginal hysterectomy and laparoscopically assisted vaginal hysterectomy can be performed in women with uterine weight of at least 450 g . Preoperative ultrasonographic examination can provide the surgeon with valuable information on the size of the fibroid and the estimated weight of the enlarged uterus before implementing a suitable surgical method.

Z Gastroenterol, 2002 Dec, 40(12), 979 - 82
{Chronic diarrhea after a journey to Sri Lanka}; Schiemann U et al.; A 51-year-old woman was referred for evaluation of chronic diarrhea . She had spent a 14 day vacation in Sri Lanka three years ago . The clinical examination of the patient was unremarkable . Values for protein, iron, zinc, copper and folic acid were decreased and the Shilling- and D-xylose tests revealed pathological results . Gliadin and Endomysium antibodies were not detectable . Histologic examination of the duodenum displayed chronic duodenitis with increased epithelial regeneration and villous atrophy . In the MRI a segment of the mid small bowel with increased thickness of the intestinal wall was described . Abdominal CT-scans demonstrated multiple, enlarged mesenteric lymph nodes . Laparoscopy with biopsies of the ileum and mesenteric lymph nodes excluded a malignant lymphoma, mycobacteriosis or Whipple's disease . Oral therapy with tetracyclines (250 mg q . i . d.) and substitution of folic acid and iron led to rapid improvement of the clinical symptoms which persisted after cessation of the antibiotic therapy . In view of the clinical course tropical sprue has to be assumed despite the short duration of the journey to a tropical region.

Cancer Res, 2003 Jan 1, 63(1), 39 - 43
Identification of ErbB-2 kinase domain motifs required for geldanamycin-induced degradation; Tikhomirov O et al.; The ansamycin antibiotic geldanamycin (GA) induces the intracellular degradation of ErbB-2/neu . Degradation of ErbB-2 proceeds through cleavage(s) within the kinase domain, resulting in the formation of a 135 kDa ectodomain fragment and a fragment(s) of approximately 50 kDa containing the COOH-terminal region . On the basis of independent means of identification, two adjacent sequence motifs have been identified in ErbB-2 that are required for GA-induced degradation . These motifs encompass residues 776-783 and 784-786 within the NH(2)-terminal lobe of the ErbB-2 kinase domain . This is also a region in which the epidermal growth factor receptor and ErbB-2 kinase domains differ significantly in sequence . Although mutations in this region abrogate GA-induced ErbB-2 degradation, the tyrosine kinase activity of ErbB-2 is not disrupted . Interestingly, these ErbB-2 mutants are specifically resistant to GA-induced degradation but retain sensitivity to other drugs, such as staurospore and curcumin, which are also able to provoke ErbB-2 degradation.

Obstet Gynecol, 2003 Jan, 101(1), 178 - 93
Preterm premature rupture of the membranes; Mercer BM; Preterm premature rupture of membranes (PROM) affects over 120,000 pregnancies annually in the United States and is associated with significant maternal, fetal, and neonatal risk . Management of PROM requires an accurate diagnosis as well as evaluation of the risks and benefits of continued pregnancy or expeditious delivery . An understanding of gestational age-dependent neonatal morbidity and mortality is important in determining the potential benefits of conservative management of preterm PROM at any gestation . Where possible, the treatment of pregnancies complicated by PROM remote from term should be directed towards conserving the pregnancy and reducing perinatal morbidity due to prematurity while monitoring closely for evidence of infection, placental abruption, labor, or fetal compromise due to umbilical cord compression . Current evidence suggests aggressive adjunctive antibiotic therapy to reduce gestational age-dependent and infectious infant morbidity . Similarly, review of evaluable data indicates that antenatal corticosteroid administration in this setting enhances neonatal outcome without increasing the risk of perinatal infection . It is not clear that tocolysis in the setting of preterm PROM remote from term reduces infant morbidity . When preterm PROM occurs near term, particularly if fetal pulmonary maturity is evident, the patient is generally best served by expeditious delivery.

Mutat Res, 2003 Jan 28, 522(1-2), 127 - 34
Effect of recombinant interferon-alpha on streptonigrin-induced chromosome aberrations and sister-chromatid exchanges in hamster cells; Bolzan AD et al.; The effect of recombinant interferon-alpha-2a (rIFN-alpha-2a) on the induction of chromosomal aberrations (CAs) and sister-chromatid exchanges (SCEs) by the radiomimetic antibiotic streptonigrin (SN, 250 ng/ml, 20 min, 37 degrees C) in Chinese hamster ovary (CHO) cells was investigated . Recombinant IFN-alpha-2a (4500-45,000 IU/ml) was added to the cell cultures 30 min before SN and left in the culture medium until the end of SN treatment or until cell harvesting . A statistically significant increase in the frequency of CAs and SCEs was observed following treatment with SN (P < 0.05), whereas treatments with rIFN-alpha-2a alone did not produce any significant increase of CAs and SCEs over control values . Low rIFN-alpha-2a doses produced a reduction in the frequency of CAs and an increase in the yield of SCEs induced by SN, while high doses of the cytokine caused an increase in the yield of CAs and a reduction in the frequency of SCEs induced by the antibiotic . In addition, rIFN-alpha-2a caused a marked inhibition (around 50%) on the yield of SN-induced chromatid-type aberrations in the G(2) phase of the cell cycle . It is suggested that the inhibitory effect of rIFN-alpha-2a on the SN-induced chromosome damage is due to the stimulation of DNA synthesis and repair by the cytokine . On the other hand, our results give further support to our previous hypothesis that the induction of CAs and SCEs by SN is based on different mechanisms .

Expert Opin Biol Ther, 2002 Dec, 2(8), 985 - 92
Pegfilgrastim; Willis F et al.; Granulocyte colony stimulating factor (G-CSF) has proven efficacy in the prophylaxis of chemotherapy induced neutropenia and is associated with a reduction in the duration of neutropenia, febrile neutropenia, hospitalisation and intravenous antibiotic use . It is an effective mobiliser of peripheral blood progenitor cells and is used in many countries to mobilise and provide a source of stem cells for autologous and allogeneic bone marrow transplantation . The longevity of G-CSF action is limited by its short half-life, necessitating daily injections . Pegfilgrastim (Neulasta, Amgen, Inc.) is a novel form of filgrastim (G-CSF) with a sustained duration of action . Single dose pegfilgrastim has been shown to be as safe and effective as daily filgrastim in reducing the incidence of chemotherapy induced neutropenia . Pegfilgrastim provides clinical and quality of life benefits for patients as a result of its once per cycle administration . It is licenced in the US for use in the prophylaxis and treatment of chemotherapy induced neutropenia . Clinical trials to evaluate its ability to mobilise peripheral blood progenitor cells are ongoing.

Infect Control Hosp Epidemiol, 2002 Dec, 23(12), 759 - 69
Guidelines for the prevention of intravascular catheter-related infections; O'Grady NP et al.; BACKGROUND: Although many catheter-related bloodstream infections (CRBSIs) are preventable, measures to reduce these infections are not uniformly implemented . OBJECTIVE: To update an existing evidenced-based guideline that promotes strategies to prevent CRBSIs . DATA SOURCES: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles . STUDIES INCLUDED: Laboratory-based studies, controlled clinical trials, prospective interventional trials, and epidemiologic investigations . OUTCOME MEASURES: Reduction in CRBSI, catheter colonization, or catheter-related infection . SYNTHESIS: The recommended preventive strategies with the strongest supportive evidence are education and training of healthcare providers who insert and maintain catheters; maximal sterile barrier precautions during central venous catheter insertion; use of a 2% chlorhexidine preparation for skin antisepsis; no routine replacement of central venous catheters for prevention of infection; and use of antiseptic/antibiotic-impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (ie, education and training, maximal sterile barrier precautions, and 2% chlorhexidine for skin antisepsis) . CONCLUSION: Successful implementation of these evidence-based interventions can reduce the risk for serious catheter-related infection.

Infect Control Hosp Epidemiol, 2002 Dec, 23(12), 748 - 56
Prevention of bloodstream infections with central venous catheters treated with anti-infective agents depends on catheter type and insertion time: evidence from a meta-analysis; Walder B et al.; OBJECTIVE: To test the evidence that the risk of infection related to central venous catheters (CVCs) is decreased by anti-infective coating or cuffing . DESIGN: Systematic review of randomized, controlled trials comparing anti-infective with inactive (control) CVCs . INTERVENTIONS: Average insertion times were taken as a measurement of the length of insertion . Dichotomous data were combined using a fixed effect model and expressed as odds ratio (OR) with 95% confidence interval (CI95) . RESULTS: Two trials on antibiotic coating (343 CVCs) had an average insertion time of 6 days; the risk of BSI decreased from 5.1% with control to 0% with anti-infective catheters . There were no trials with longer average insertion times . In three trials on silver collagen cuffs (422 CVCs), the average insertion time ranged from 5 to 8.2 days (median, 7 days); the risk of BSI was 5.6% with control and 3.2% with anti-infective catheters . In another trial on silver collagen cuffs (101 CVCs), the average insertion time was 38 days; the risk of BSI was 3.7% with control and 4.3% with anti-infective catheters . In five trials on chlorhexidine-silver sulfadiazine coating (1,269 CVCs), the average insertion time ranged from 5.2 to 7.5 days (median, 6 days); the risk of BSI decreased from 4.1% with control to 1.9% with anti-infective catheters . In five additional trials on chlorhexidine-silver sulfadiazine coating (1,544 CVCs), the average insertion time ranged from 7.8 to 20 days (median, 12 days); the risk of BSI was 4.5% with control and 4.2% with anti-infective catheters . CONCLUSIONS: Antibiotic and chlorhexidine-silver sulfadiazine coatings are anti-infective for short (approximately 1 week) insertion times . For longer insertion times, there are no data on antibiotic coating, and there is evidence of lack of effect for chlorhexidine-silver sulfadiazine coating . For silver-impregnated collagen cuffs, there is evidence of lack of effect for both short- and long-term insertion.

Can J Ophthalmol, 2002 Dec, 37(7), 395 - 8
Do we heed the endophthalmitis vitrectomy study in Canada?
Siddiqui F, Crippen C, Hutnik CM.
BACKGROUND: The Endophthalmitis Vitrectomy Study (EVS) was a multicentre randomized clinical trial designed to guide the management of postoperative bacterial endophthalmitis . There is speculation that many physicians do not follow its recommendations, despite its intent . We surveyed Canadian vitreoretinal surgeons to determine whether surgeons are adopting the EVS recommendations in their management of bacterial endophthalmitis after cataract surgery . METHODS: A survey was sent to 98 vitreoretinal surgeons across Canada who manage postoperative endophthalmitis following cataract surgery . The survey explored the management of patients presenting with a hypopyon or suspected endophthalmitis, or both, early (up to 2 weeks) after cataract surgery . For purposes of comparison with the EVS, the questions were divided into presenting visual acuity categories . RESULTS: Of the 98 surgeons 30 (30.6%) responded to the survey . The preferred treatment for patients presenting with no light perception visual acuity was pars plana vitrectomy (23 respondents {76.7%}); 7 respondents (23.3%) preferred vitreous tap/biopsy . All but one of the respondents stated that they prefer pars plana vitrectomy for patients presenting with light perception vision; the remaining physician preferred either pars plana vitrectomy or vitreous tap/biopsy . For patients with hand motions visual acuity, 17 respondents (56.7%) would perform pars plana vitrectomy, 11 (36.7%) would perform vitreous tap/biopsy, and 2 (6.7%) would perform either procedure . Most of the respondents (20 {66.7%}) would perform vitreous tap/biopsy for patients with visual acuity of counting fingers, whereas 9 (30.0%) would perform pars plana vitrectomy, and 1 (3.3%) would perform either procedure . All the respondents indicated that they would use intraocular antibiotic therapy for initial treatment, 29 (96.7%) would use topical antibiotic therapy, 17 (56.7%) would inject antibiotics subconjunctivally, and 1 (3.3%) would use intravenous antibiotic therapy . Fourteen respondents (46.7%) would use intraocular steroid therapy . INTERPRETATION: Most of the Canadian vitreoretinal surgeons who responded to this survey do not follow the recommendations of the EVS.

J Org Chem, 2003 Jan 10, 68(1), 130 - 8
Formal enantiospecific synthesis of (+)-FR900482; Paleo MR et al.; The enantiospecific synthesis of FK973, and thus a formal enantiospecific synthesis of the antitumor antibiotic (+)-FR900482, is reported . Addition of aniline 8 to chiral epoxide 9, prepared from l-vinylglycine, afforded amino alcohol 12 . After protection of the aliphatic nitrogen with the 9-phenylfluoren-9-yl group, to preserve the acidic stereocenter from racemization, formation of the aziridine 14 and intramolecular condensation under basic conditions gave azocinone 15 . Hydroxymethylation at the benzylic position was achieved by a process involving methylenation, epoxidation, and hydrogenolysis; the absolute stereochemistry of the resulting alcohol 23 was determined by X-ray crystallographic analysis . The hydroxyl group of 23 was carbamoylated, and the aromatic amine was deprotected electrochemically and then oxidized to give an unstable hydroxylamine that was immediately protected as acetate 26 . Oxidation of 26 with DMP, followed by hydrazinolysis of the acetyl group led to spontaneous closure of the resulting N-hydroxyamino ketone to hemiketal 28, which can be considered as a fully protected precursor of FR900482 and derivatives . Acid treatment to remove the protecting groups and acetylation afforded the triacetate FK973.

J S Afr Vet Assoc, 2002 Sep, 73(3), 133 - 4
Suspected primary immune deficiency in a Donge de Bordeaux dog; Lobetti RG; A young Donge de Bordeaux dog was presented with chronic intermittent antibiotic responsive gastrointestinal and respiratory disease . Further evaluation showed bacterial lymphadenitis, bacterial tracheitis, normal white cell and differential cell counts, hypogammaglobulinaemia, and the absence of B-lymphocytes but the presence of T-lymphocytes in the lymphoid tissue stained with lymphocyte markers . As the dog came from a narrow genetic base, with related dogs showing similar clinical signs, possible B-cell congenital immune deficiency was suspected.

Khirurgiia (Sofiia), 2002, 58(1), 24 - 7
{Surgical treatment of post-traumatic intrapulmonary haematomas}; Obretenov E et al.; In a 14-year period 18 patients with post-traumatic intrapulmonary haematomas (PIH) were diagnosed and treated in our departments . There were 14 men and 4 woman with mean age 42.1 year . The mean diameter of PIH was 7.5 cm and they were localized mainly in the left lower lobe . Three of the patients were successfully treated with conservative antibiotic and mucolytic therapy . The remaining 15 patients (83%) were operated on: lobectomy (7), segmental resection (2), extirpation with partial resection of the fibrous capsule and capitonnage (4) and total extirpation with fibrous capsule removal (2) . Indications for surgery were as follows: infection, haemoptysis and suspicions of malignant lesion . The early and late results are excellent . We recommend the surgical approach to PIH as a safe and effective treatment.

Liver Transpl, 2003 Jan, 9(1), 22 - 30
ABO-incompatible liver transplantation with no immunological graft losses using total plasma exchange, splenectomy, and quadruple immunosuppression: evidence for accommodation; Hanto DW et al.; ABO-incompatible liver transplants (LTX) have been associated with a high risk of antibody-mediated rejection, poor patient and graft survival, and a high risk of vascular thrombosis and ischemic bile duct complications . We used pretransplantation and posttransplantation double-volume total plasma exchange (TPE), splenectomy, and quadruple immunosuppression (cyclophosphamide or mycophenolate mofetil, prednisone, cyclosporine or tacrolimus, and OKT3 induction) in 14 patients receiving ABO-incompatible LTX between June 1992 and February 2001: A(1) to O (seven), B to O (two), B to A (two), A to B (one), AB to A (one), and AB to O (one) . Actuarial 1- and 5-year patient and graft survival rates are 71.4% and 61.2 % and 71.4% and 61.2%, respectively, with a mean follow-up of 62.9 +/- 39.4 months . Ten acute cellular rejections occurred, and the mean time to the first episode was 62 +/- 33 days . All were steroid sensitive . No antibody-mediated rejection or vascular thromboses occurred . Pretransplantation pre-TPE immunoglobulin (Ig) G mean isohemagglutinin titers were 262 +/- 326, compared with pretransplantation post-TPE titers of 65 +/- 103 (P =.04) . Eight of nine patients with measurable titers before and after TPE achieved a reduction in titers . The mean number of posttransplantation TPE was 5.5 +/- 4.1 (range, 0 to 12), and the last TPE was on postoperative day 9.4 +/- 5.3 . IgG isohemagglutinin titers 2 weeks posttransplantation had increased to 153 +/- 309 (P =.03 compared with pretransplantation pre-TPE IgG) . ABO-incompatible liver transplantations can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with a combination of TPE, splenectomy, and quadruple immunosuppression . Recovery of isohemagglutinin antibody levels without humoral rejection suggests that accommodation may be the protective mechanism preventing late antibody-mediated rejection.

Appl Environ Microbiol, 2003 Jan, 69(1), 517 - 23
Gene replacement in mycobacteria by using incompatible plasmids; Pashley CA et al.; A simple and efficient delivery system was developed for making targeted gene knockouts in Mycobacterium smegmatis . This delivery system relies on the use of a pair of replicating plasmids, which are incompatible . Incompatible plasmids share elements of the same replication machinery and so compete with each other during both replication and partitioning into daughter cells . Such plasmids can be maintained together in the presence of antibiotics; however, removal of selection leads to the loss of one or both plasmids . For mutagenesis, two replicating plasmids based on pAL5000 are introduced; one of these plasmids carries a mutated allele of the targeted gene . Homologous recombination is allowed to take place, and either one or both of the vectors are lost through the pressure of incompatibility, allowing the phenotypic effects of the mutant to be studied . Several different plasmid combinations were tested to optimize loss in the absence of antibiotic selection . pAL5000 carries two replication genes (repA and repB), which act in trans, and the use of vectors that each lack one rep gene and complement each other resulted in the loss of both plasmids in M . smegmatis and Mycobacterium bovis BCG . The rate of loss was increased by the incorporation of an additional incompatibility region in one of the plasmids . To facilitate cloning when the system was used, we constructed plasmid vector pairs that allow simple addition of selection and screening genes on flexible gene cassettes . Using this system, we demonstrated that M . smegmatis pyrF mutants could be isolated at high frequency . This method should also be useful in other species in which pAL5000 replicates, including Mycobacterium tuberculosis.

Appl Environ Microbiol, 2003 Jan, 69(1), 84 - 91
Intergeneric conjugation in Streptomyces peucetius and Streptomyces sp . strain C5: chromosomal integration and expression of recombinant plasmids carrying the chiC gene; Paranthaman S et al.; Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to Streptomyces circumvents problems such as host-controlled restriction and instability of foreign DNA during the transformation of Streptomyces protoplasts . The anthracycline antibiotic-producing strains Streptomyces peucetius and Streptomyces sp . strain C5 were transformed using E . coli ET12567(pUZ8002) as a conjugal donor . When this donor species, carrying pSET152, was mated with Streptomyces strains, the resident plasmid was mobilized to the recipient and the transferred DNA was also integrated into the recipient chromosome . Analysis of the exconjugants showed stable integration of the plasmid at a single chromosomal site (attB) of the Streptomyces genome . The DNA sequence of the chromosomal integration site was determined and shown to be conserved . However, the core sequence, where the crossover presumably occurred in C5 and S . peucetius, is TTC . These results also showed that the phiC31 integrative recombination is active and the phage attP site is functional in S . peucetius as well as in C5 . The efficiency and specificity of phiC31-mediated site-specific integration of the plasmid in the presence of a 3.7-kb homologous DNA sequence indicates that integrative recombination is preferred under these conditions . The integration of plasmid DNA did not affect antibiotic biosynthesis or biosynthesis of essential amino acids . Integration of a single copy of a mutant chiC into the wild-type S . peucetius chromosome led to the production of 30-fold more chitinase.

Paediatr Drugs, 2003, 5(1), 41 - 56
Quality of life in children and adolescents with cystic fibrosis: implications for optimizing treatments and clinical trial design; Abbott J et al.; Health related quality of life (QOL) as an outcome measure in clinical trials is becoming increasingly important . Trials should not only be able to demonstrate the pharmacologic activity of a therapy, but of equal importance, they should demonstrate clinical effectiveness that is of significant benefit to the patient . QOL measurement provides a way of incorporating the child/parent's perspective of how cystic fibrosis (CF) and its therapies impact on their lives . Several validated generic instruments have been employed to measure QOL in adolescents and adults . QOL assessment is more difficult in children and, therefore, has been employed less often in children with CF . Difficulties arise with the issue of whether children can report their own experiences directly, or whether a parent or clinician should report on behalf of the child . A child-centered approach is imperative since the literature indicates that children are able to report on their own QOL . An additional complication has been the use of adult measures with children . These are often inappropriate in their complexity, use of language, response scales, and time frame . The evaluation of pharmacologic therapies can profit from QOL measurement . The effectiveness of a drug and any adverse effects that impact on daily life can be assessed from the child/parent's viewpoint . Home therapy versus hospital therapy and drug delivery systems, are additional areas where QOL as an outcome measure is valuable . There have been relatively few appropriately powered trials in CF, and only a minority of these have evaluated QOL as an outcome measure . This review highlights areas where QOL measurement is appropriate . It focuses on the pharmacologic trials that have employed QOL assessment for antibiotic, mucociliary clearance, anti-inflammatory, and nutritional therapies . Methodological issues of incorporating QOL assessment into trials center on cross-cultural and data interpretation issues . QOL measurement in CF has been patchy and largely unreliable . The notion that improved symptoms equate with improved QOL is erroneous . Measurement of how symptoms impact on QOL is essential . Currently, the development and validation of CF specific measures (across the CF age range) provides optimism for appropriate QOL measurement in clinical trials, and for future meta-analysis and systematic reviews.

Infect Dis Clin North Am, 2002 Dec, 16(4), 821 - 35
Deeply invasive candidiasis; Ostrosky-Zeichner L et al.; The incidence of invasive candidiasis is on the rise because of increasing numbers of immunocompromised hosts and more invasive medical technology . Recovery of Candida spp from several body sites in a critically ill or immunocompromised patient should raise the question of disseminated disease . Although identification to the species level and antifungal susceptibility testing should guide therapy, at this time amphotericin B preparations are the usual initial therapy for severe life-threatening disease . Azole therapy has an expanding body of evidence that proves it is as effective as and safer than amphotericin B therapy . Some forms of candidiasis (e.g., those with ocular, bone, or heart involvement) require a combined medical and surgical approach.

J Bacteriol, 2003 Jan, 185(2), 592 - 600
Accumulation of S-adenosyl-L-methionine enhances production of actinorhodin but inhibits sporulation in Streptomyces lividans TK23; Kim DJ et al.; S-Adenosyl-L-methionine synthetase (SAM-s) catalyzes the biosynthesis of SAM from ATP and L-methionine . Despite extensive research with many organisms, its role in Streptomyces sp . remains unclear . In the present study, the putative SAM-s gene was isolated from a spectinomycin producer, Streptomyces spectabilis . The purified protein from the transformed Escherichia coli with the isolated gene synthesized SAM from L-methionine and ATP in vitro, strongly indicating that the isolated gene indeed encoded the SAM-s protein . The overexpression of the SAM-s gene in Streptomyces lividans TK23 inhibited sporulation and aerial mycelium formation but enhanced the production of actinorhodin in both agar plates and liquid media . Surprisingly, the overexpressed SAM was proven by Northern analysis to increase the production of actinorhodin through the induction of actII-ORF4, a transcription activator of actinorhodin biosynthetic gene clusters . In addition, we found that a certain level of intracellular SAM is critical for the induction of antibiotic biosynthetic genes, since the control strain harboring only the plasmid DNA did not show any induction of actII-ORF4 until it reached a certain level of SAM in the cell . From these results, we concluded that the SAM plays important roles as an intracellular factor in both cellular differentiation and antibiotic production in Streptomyces sp.

Acta Orthop Traumatol Turc, 2002, 36(1), 52 - 7
{Treatment of childhood unstable radius distal methaphysis fractures with closed reduction and percutaneous Kirschner wires}; Muratli HH et al.; OBJECTIVES: We evaluated the results of treatment with closed reduction and percutaneous Kirschner wires in childhood unstable radius distal methaphysis fractures . METHODS: Forty-four fractures of radius distal methaphysis of 43 children (33 boys, 10 girls; mean age 11.7 years; range 8.6 to 16 years) were treated with immediate closed reduction and percutaneous Kirschner wires . Fractures with more than 50% displacement were considered unstable . A satisfactory reduction was defined as the presence of 80% cortical contact on anteroposterior and lateral x-rays, an angulation of less than 20 degrees and 15 degrees at ages below and over 10 years, respectively, and the absence of malrotation . Clinically, the range of motion of the elbow and wrist, forearm rotation, and grip strength were measured and compared with those of the other side in the 12th postoperative week . A restriction of 10 degrees or more in relation to the other side was regarded as failure . Radiologic indications of failure in the postoperative sixth week were residual angulations of more than 15 degrees and 10 degrees at ages below and above 10 years, respectively, and malrotation . RESULTS: Forty-one patients (93.2%) achieved a successful outcome . Failure was encountered in three patients (6.8%) . Two patients developed type 1 pin tract infection, which resolved with antibiotic therapy and wound care . Patients returned to their normal activities in a mean of 10 weeks . CONCLUSION: Closed reduction and the use of percutaneous Kirschner wires proved to be the choice of treatment in unstable radius distal methaphysis fractures in children.

Fam Pract, 2003 Feb, 20(1), 69 - 73
Understanding variation in quality improvement: the treatment of sore throats in primary care; Marshall T et al.; BACKGROUND: In 1988, two practices attempted to improve the prescribing of antibiotics for sore throat . The initiative produced only modest improvements in prescribing practice, a finding the authors found difficult to explain . This paper reanalyses the data from an audit of antibiotic prescribing for sore throat in general practice . OBJECTIVE: Our aim was to demonstrate the use of Shewhart control charts and to obtain fresh insight into the variations in clinical practice revealed in clinical audit data . METHODS: We use Shewhart control charts to explore variation in antibiotic prescribing between GPs and to suggest the action most likely to result in improvement . RESULTS: Using control charts, it is possible to distinguish two categories of GPs: low prescribers of antibiotics and high prescribers of antibiotics . Low prescribers of antibiotics show common cause variation, indicating that their prescribing is a stable process . Among low prescribers, improvement can best be achieved by changing the common underlying process . One high prescriber of antibiotics is affected by special cause variation . Among high prescribers, improvement can best be achieved by investigating the special causes affecting this GP and learning lessons from the findings . CONCLUSION: The original improvement effort took the same action on all GPs in both practices . Our analysis suggests that such an approach was unlikely to be successful and that different actions were needed for high and low prescribers . The control charts provide fresh insights on the original data and guide improvement efforts.

J Clin Epidemiol, 2002 Nov, 55(11), 1148 - 55
Improving private pharmacy practice: a multi-intervention experiment in Hanoi, Vietnam; Chuc NT et al.; The objective of this study was to assess the effects of a multicomponent intervention on private pharmacy practice . From 641 private pharmacies in Hanoi, 68 pharmacies were randomly selected and matched into 34 pairs . Each pair consisted of a control and an intervention pharmacy . Three interventions were applied sequentially: Regulatory enforcement, Education, and Peer influence . Four tracer conditions were selected: uncomplicated acute respiratory infection (ARI), sexually transmitted disease (STD), requesting the prescription-only drugs prednisolone, and a short course of cefalexin . Practice was assessed through the Simulated Client Method (SCM) . The intervention pharmacies improved significantly compared to the control pharmacies (P <.05) in all tracer conditions . For ARI, antibiotic dispensing decreased (P <.02) and questions regarding breathing increased (P <.01) . For STD, advice to go to the doctor and dispensing the correct syndromic treatment increased (P <.01) . Dispensing of prednisolone and cefalexin decreased (P <.01) and prescription requests increased (P <.01) . Our conclusion is that it is possible to improve private pharmacy practice with a multicomponent intervention.

Chemistry, 2003 Jan 3, 9(1), 260 - 70
Enantioselective synthesis of paraconic acids; Chhor RB et al.; The development of a new method for the enantioselective synthesis of disubstituted gamma-butyrolactones is reported . Based on this strategy, the total synthesis of three paraconic acids, that is (-)-roccellaric acid, (-)-nephrosteranic acid and (-)-protopraesorediosic acid, and the formal total synthesis of (-)-methylenolactocin and (-)-protolichesterinic acid is described, which are important because of their antibiotic and antitumor properties . Key steps of the synthesis are copper(I)-catalyzed asymmetric cyclopropanations of furans, highly diastereoselective Sakurai allylations, Lewis acid or Lewis base catalyzed retroaldol/lactonization cascades, and ruthenium(II)-catalyzed, intermolecular cross metathesis reactions.

J Am Soc Nephrol, 2003 Jan, 14(1), 169 - 79
Hemodialysis infection prevention with polysporin ointment; Lok CE et al.; Hemodialysis patients in whom permanent vascular access cannot be achieved are dependent on a central venous catheter . In such patients, catheter-related infections are a common and serious complication . This study was a randomized clinical trial to determine if topical Polysporin Triple antibiotic ointment applied to the central venous catheter insertion site could reduce the incidence of catheter-related infections . A total of 169 patients receiving hemodialysis through a central venous catheter were randomized to receive Polysporin Triple or placebo using a double-blind study design . In the 6-mo study period, infections were observed in more patients in the placebo group than in the Polysporin Triple group (34 versus 12%; relative risk, 0.35; 95% CI, 0.18 to 0.68; P = 0.0013) . The number of infections per 1000 catheter days (4.10 versus 1.02; P < 0.0001) and the number of bacteremias per 1000 catheter days (2.48 versus 0.63; P = 0.0004) were also greater in the placebo group . Within the 6-mo study period, there were 13 deaths in the placebo group as compared with 3 deaths in the Polysporin Triple group (P = 0.0041) . When all available follow-up information was included, the difference in survival remained significant (19 versus 9 deaths; P = 0.0027) . Within the first 6 mo, infections were observed in 7 of the 13 placebo subjects who died (54%) as compared with no infections in the three Polysporin Triple subjects who died . The prophylactic application of topical Polysporin Triple antibiotic ointment to the central venous catheter insertion site reduced the rate of infections and was associated with improved survival in hemodialysis patients.

BJOG, 2002 Dec, 109(12), 1341 - 3
The effect of the publication of a major clinical trial in a high impact journal on clinical practise: the ORACLE Trial experience; Kenyon S et al.; OBJECTIVE: To estimate the short term effect of the publication of a major clinical trial on clinical practise . DESIGN: Questionnaire survey of clinical practise . SETTING: UK . POPULATION: All maternity units in the UK . METHOD: A self-administered questionnaire completed by lead consultants on delivery suite of maternity units . MAIN OUTCOME MEASURES: Changes in antibiotic prescription . RESULTS: Within six months of publication, approximately 50% of maternity units had changed their guidelines for the care of women with preterm prelabour rupture of the fetal membranes . CONCLUSION: Publication of a major clinical trial does impact on clinical practise but the impact is heterogeneous in terms of time and consistency.

Ann Pharmacother, 2003 Jan, 37(1), 57 - 60
Fulminant liver failure associated with clarithromycin; Tietz A et al.; OBJECTIVE: To report a patient developing fulminant liver failure while being treated with clarithromycin for pneumonia . CASE SUMMARY: A 58-year-old white woman developed fulminant liver failure while being treated with the macrolide antibiotic clarithromycin for pneumonia . Comedication included N-acetylcysteine, atenolol, and isradipine . Other causes of liver failure, such as viral hepatitis, autoimmune hepatitis, toxins, and heart failure, were excluded by appropriate diagnostic means . All drugs were stopped, and the patient was transferred to another hospital for liver transplantation . She recovered spontaneously within several days, making transplantation unnecessary . A liver biopsy obtained 10 days after the initial presentation revealed centroacinar necrosis and beginning fibrous reorganization, compatible with recent centroacinar damage . DISCUSSION: Since no other cause could be identified, liver injury was considered to be drug related . Fulminant liver failure has not previously been described with concomitant use of atenolol and N-acetylcysteine . Although isradipine has been associated with hepatocellular injury, there are no reports of fulminant liver failure with this agent, and our patient had been treated for >2 years without signs of toxicity . The most likely cause of liver failure in this patient was, therefore, clarithromycin, which undergoes hepatic metabolism and has been reported to cause fulminant hepatic failure . A second possibility is an interaction between clarithromycin and isradipine, potentially increasing the hepatic toxicity of isradipine . CONCLUSIONS: Clarithromycin may be a cause of fulminant liver failure either alone or by inhibiting the metabolism of other drugs.

Expert Rev Anticancer Ther, 2002 Dec, 2(6), 630 - 40
Gemtuzumab ozogamicin: promise and challenge in patients with acute myeloid leukemia; Giles FJ; CD33 is a suitable target to guide delivery of a toxic moiety to most acute myeloid leukemia cells . Gemtuzumab ozogamicin (Mylotarg) is a humanized antiCD33 monoclonal antibody covalently linked to a derivative of a cytotoxic antibiotic, calicheamicin . As a single agent, gemtuzumab ozogamicin has activity (complete remission rate of 15-20%) in patients with relapsed disease . Gemtuzumab ozogamicin-based combinations are being studied as induction, maintenance and relapse regimens . The chemical hepatotoxicity often observed with gemtuzumab ozogamicin therapy is of little clinical consequence . However, hepatic veno-occlusive disease is a relatively frequent and serious toxicity for which no clear risk factors, other than stem cell transplantation, have been defined . Gemtuzumab ozogamicin-based regimens may be particularly worthy of study in patients with acute promyelocytic leukemia . Gemtuzumab ozogamicin is approved as single-agent therapy for patients over the age of 60 years in first relapse who are not considered candidates for cytotoxic therapy . The administration of gemtuzumab ozogamicin should be carried out under a level of supervision commensurate with that afforded other intensely myelosuppressive agents . Gemtuzumab ozogamicin-based combinations should not be prescribed outside the research setting until further data is available.

Cornea, 2003 Jan, 22(1), 66 - 9
Late traumatic displacement of laser in situ keratomileusis flaps; Tumbocon JA et al.; PURPOSE: To report the occurrence, management, and outcome of late-onset traumatic dehiscence and dislocation of laser in situ keratomileusis (LASIK) flaps . METHODS: Two interventional case reports of patients with late-onset LASIK corneal flap dislocation after ocular trauma occurring at 7 and 26 months after surgery, respectively . RESULTS: The flaps were lifted, stretched, and repositioned after irrigation and scraping of the stromal bed and the underside of the flap . A bandage contact lens was placed, and topical antibiotic and corticosteroids were given postoperatively . The dislocated corneal flaps were successfully repositioned in both cases . The patient whose dislocated flap was repositioned 4 hours after the trauma recovered his uncorrected visual acuity (UCVA) of 20/20 1 week after the procedure and had a well-positioned flap with a clear interface . The patient who was managed 48 hours after the injury required repeat flap repositioning at 10 and 24 days after the initial procedure for treatment of persistent folds and striae in the visual axis . His uncorrected visual acuity 2 weeks after the third flap repositioning was 20/40 + 2 . Diffuse lamellar keratitis developed in both patients that resolved with the use of topical corticosteroids . CONCLUSION: Laser in situ keratomileusis corneal flaps are vulnerable to traumatic dehiscence and dislocation, which can occur more than 2 years after the procedure.

J Biol Chem, 2003 Mar 7, 278(10), 7844 - 9 Epub 2002 Dec 26.
The mmaA2 gene of Mycobacterium tuberculosis encodes the distal cyclopropane synthase of the alpha-mycolic acid; Glickman MS; Infection with Mycobacterium tuberculosis (Mtb) remains a severe global health problem that has prompted an aggressive search for new antibiotic targets and vaccine strategies for this persistent pathogen . Recently, a wide variety of genetic determinants of Mtb pathogenicity have been identified, including several genes involved in the biogenesis of the complex Mtb cell envelope . Among these are the mycolic acid cyclopropane synthases, a family of proteins that modify the major cell envelope lipids of Mtb with a diversity of cyclopropane rings . Despite substantial sequence identity, these proteins catalyze highly specific cyclopropane modifications, including proximal modification of the alpha-mycolate (pcaA) and trans-cyclopropane modification (cmaA2) . Here we report the mycolic acid modification function of a third cyclopropane synthase, mmaA2, through the creation and analysis of an M . tuberculosis mmaA2 null mutant . Unexpectedly, mmaA2 is essential for the distal cyclopropane modification of the alpha-mycolate, a function previously attributed to cmaA1 . alpha-Mycolates of a cmaA1 null mutant were unaffected, demonstrating that cmaA1 is not required for alpha-mycolate modification . Although fully cyclopropanated methoxymycolates are produced in the mmaA2 mutant, cis-cyclopropanation is impaired, leading to accumulation of unsaturated methoxymycolate derivatives . This study establishes mmaA2 as a distal cyclopropane synthase of the alpha-mycolates of M . tuberculosis and the first cyclopropane synthase to modify both alpha- and oxygenated mycolates . These results expand our knowledge of the biosynthesis of the Mtb cell envelope and will allow further elucidation of the relationship between Mtb pathogenesis and the fine structure of mycolic acids.

Mil Med, 2002 Dec, 167(12), 978 - 81
The treatment of infected tibial nonunion with aggressive debridement and internal bone transport; Atesalp AS et al.; Tibial nonunions are a challenging situation for both healing and reconstruction when infection is added . In this retrospective study, we discuss the cases in which we had managed to obtain union by aggressive debridement, circular external fixature, and internal bone transport . Fourteen cases had been treated between January 1995 and December 2000 in the Orthopedics and Traumatology Department of the Gulhane Military Medical Academy . The mean follow-up period was 33.2 (12-60 months) months . The mean length of defects was 4.4 (2.5-8 cm) cm . These defects were repaired by corticotomy and by internal bone transport only . Pseudoarthrosis and union of corticotomy sites occurred in a mean period of 6.8 (4.5-15) months . In two of our patients, reinfection occurred, and hyperbaric oxygen therapy was applied to them . We concluded that in tibial infected nonunions, satisfactory union and control of infection are possible by radical debridement, stable fixation by circular external fixature, osteotomy and callus distraction, antibiotic therapy, and hyperbaric oxygen therapy whenever needed.

Clin Ther, 2002 Nov, 24(11), 1824 - 39
The effect of zanamivir treatment on influenza complications: a retrospective cohort study; Cole JA et al.; BACKGROUND: Complications of influenza are a major cause of morbidity and mortality during the influenza season . Clinical trials of zanamivir have reported a reduced incidence of influenza complications among high-risk patients . OBJECTIVES: This retrospective study sought to determine whether the use of zanamivir lowers the risk of acute influenza complications in a broader population, based on an analysis of claims data from a large managed care organization . METHODS: Medical and pharmacy health insurance claims data from October 1, 1999, through April 30, 2000, were compiled for UnitedHealthcare members in 19 states . All patients with a diagnosis of influenza (International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code 487.xx) associated with a physician visit were identified . From these, all patients were selected who had received zanamivir on the same day as the diagnosis of influenza . The propensity score matching technique was used to identify a comparison group with similar health service utilization and comorbidities who received a diagnosis of influenza but no antiviral therapy . Follow-up started the day after the influenza diagnosis and continued for 21 days . RESULTS: From the 43,741 patients originally identified, 2341 were selected who received a simultaneous diagnosis of influenza and a prescription for zanamivir . The untreated comparator group numbered 2337 . Fewer zanamivir patients than untreated patients were hospitalized for complications, and the absolute risks were low (0.6% and 1.0%, respectively; risk ratio {RR}, 0.58; 95% CI, 0.30-1.12) . Zanamivir-treated patients had an excess of outpatient visits (16.9% vs 14.5%; RR, 1.16; 95% CI, 1.02-1.33) and antibiotic use (16.3% vs 14.8%; RR, 1.10; 95% CI, 0.97-1.26), although the RRs were modest . CONCLUSIONS: In the setting of a large managed care plan, patterns of influenza complications were similar in zanamivir-treated and untreated patients with a diagnosis of influenza . The results of this study are in contrast to those of published clinical trials reporting a reduction in the risk of influenza complications in zanamivir-treated patients.

Antimicrob Agents Chemother, 2003 Jan, 47(1), 371 - 4
Penetration of fosfomycin into inflammatory lesions in patients with cellulitis or diabetic foot syndrome; Legat FJ et al.; We investigated the distribution of the broad-spectrum antibiotic fosfomycin in infected soft tissue of patients with uncomplicated cellulitis of the lower extremities or diabetic foot infection using in vivo microdialysis . Our findings suggest that fosfomycin exhibits good and similar penetration into the fluid in the interstitial space in inflamed and noninflamed soft tissue in patients.

Emerg Infect Dis, 2002 Dec, 8(12), 1433 - 41
Using automated health plan data to assess infection risk from coronary artery bypass surgery; Platt R et al.; We determined if infection indicators were sufficiently consistent across health plans to allow comparison of hospitals' risks of infection after coronary artery bypass surgery . Three managed care organizations accounted for 90% of managed care in eastern Massachusetts, from October 1996 through March 1999 . We searched their automated inpatient and outpatient claims and outpatient pharmacy dispensing files for indicator codes suggestive of postoperative surgical site infection . We reviewed full text medical records of patients with indicator codes to confirm infection status . We compared the hospital-specific proportions of cases with an indicator code, adjusting for health plan, age, sex, and chronic disease score . A total of 536 (27%) of 1,953 patients had infection indicators . Infection was confirmed in 79 (53%) of 149 reviewed records with adequate documentation . The proportion of patients with an indicator of infection varied significantly (p < 0.001) between hospitals (19% to 36%) and health plans (22% to 33%) . The difference between hospitals persisted after adjustment for health plan and patients' age and sex . Similar relationships were observed when postoperative antibiotic information was ignored . Automated claims and pharmacy data from different health plans can be used together to allow inexpensive, routine monitoring of indicators of postoperative infection, with the goal of identifying institutions that can be further evaluated to determine if risks for infection can be reduced.

Vopr Med Khim, 2002 Sep-Oct, 48(5), 469 - 76
{Transfection of eucaryotic cells using cytochrome CYP450 2B6 gene: sensitivity to cyclophosphamide}; Kolomeichuk SN et al.; Sensitivity of 293 human epithelial kidney cells transfected by human cytochrome CYP450 gene to cyclophosphamide was investigated . Transfection was carried out by plasmid DNA containing CYP2B6 gene complexed with cationic liposomes . Liposomes were prepared from mixture of cationic lipids and cholesterol at different molar ratios . Experimental protocol included the following steps: transfection of epithelial kidney cells by complexes of plasmid DNA-cationic liposomes, clone selection in the medium with antibiotic Geneticin G418, selected clone harvesting and their treatment by cyclophosphamide as following cytotoxicity evaluation . It was shown that addition of 0.25 mM of cyclophosphamide resulted in death of 40-45% transfected cell population.

Ned Tijdschr Geneeskd . 2002 Nov 30;146(48):2294.
{Diagnostic image (116) . A man with acute exanthema . Epstein-Barr virus infection}; Hanselaar WE et al.; A 19-year-old man presented with a rash, several days after antibiotic therapy for pharyngitis . Such a rash is highly suggestive of an acute viral infection; Epstein-Barr virus infection was confirmed serologically.

MMW Fortschr Med, 2002 Oct 31, 144(44), 36 - 8
{Complications of rhinosinusitis}; Grevers G et al.; Rhinogenous complications may manifest in the region of the orbits, bone or soft parts of the wall of the frontal sinus, or endocranially . With regard to orbital complications, a differentiation is made between edema, periostitis, subperiosteal abscess and phlegmon--depending on severity and extent . A possible sequela of frontal sinusitis may be osteomyelitis . If the frontal bone is involved, there is a danger that the infection may spread to the endocranium via medullary spaces and blood vessels . The diagnostic basis for deciding appropriate treatment is CT or MRI . While orbital edema and periostitis usually respond to conservative treatment, subperiosteal abscess, orbital phlegmon and abscess of the brain require immediate operative treatment under antibiotic cover . The treatment of choice for osteomyelitis of the frontal bone is the liberal removal of affected bone, also under antibiotic cover.

J Antimicrob Chemother, 2003 Jan, 51(1), 101 - 6
Pharmacokinetic aspects of levofloxacin 500 mg once daily during sequential intravenous/oral therapy in patients with lower respiratory tract infections; Furlanut M et al.; Levofloxacin is considered an effective antibiotic in the treatment of community-acquired lower respiratory tract infections (LRTIs) . A study was carried out on 17 in-patients to assess the pharmacokinetics of a 500 mg once-daily switch intravenous (i.v.)/oral regimen of levofloxacin in the treatment of LRTI patients . Blood samples were collected under steady-state conditions at appropriate intervals . Levofloxacin plasma concentrations were analysed by means of HPLC and pharmacokinetic parameters were estimated using the WinNonlin pharmacokinetic software package . A lower clearance of levofloxacin (<2 mL/min/kg), conditioning both a longer elimination half-life (approximately 9 h) and a larger AUC(0-tau) (approximately 80 mg/L x h), was observed for both routes in our patients than in healthy volunteers . These differences may be explained considering that levofloxacin is excreted mainly as unchanged drug by the renal route, and most of our patients (71%) were very elderly subjects whose renal function physiologically declines with age . The almost complete (> or =99%) absolute oral bioavailability suggests that a comparable exposure to the iv regimen may be achieved after oral administration . The overall clinical success rate was 94.1%.

Eur J Cardiothorac Surg, 2003 Jan, 23(1), 131 - 3
Pneumopericardium due to intrapericardial perforation of a gastric ulcer; Gabor S et al.; A 88-year-old male patient presented with fever, singultus and retrosternal pain . After 8 days of antibiotic therapy not resulting in clinical improvement, he suddenly developed a pneumopericardium . Contrast swallow and endoscopy showed intrapericardial perforation of a benign gastric ulcer . Excision of the ulcer and suturing of both the stomach and the diaphragm as well as lavage of the pericardium were done over a left thoracotomy . The patient recovered uneventfully.

Aliment Pharmacol Ther, 2003 Jan, 17(1), 119 - 23
Efficacy of triple therapy comprising rabeprazole, amoxicillin and metronidazole for second-line Helicobacter pylori eradication in Japan, and the influence of metronidazole resistance; Murakami K et al.; BACKGROUND: The widespread use of eradication therapy for Helicobacter pylori in Japan has led to an increase in antibiotic-resistant strains and the problem of re-treatment in cases of eradication failure . AIM: To perform drug sensitivity testing for metronidazole in 92 H . pylori-positive patients who had failed eradication treatment with first-line triple therapy, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, and were administered metronidazole-containing second-line therapy . METHODS: Second-line eradication therapy, consisting of rabeprazole (20 mg b.d.), amoxicillin (750 mg b.d.) and metronidazole (250 mg b.d.), was administered for 1 week and the eradication rates and influence of metronidazole resistance were determined . RESULTS: The eradication rates for rabeprazole-amoxicillin-metronidazole were 88% (81/92) using intention-to-treat analysis and 91% (81/89) using per protocol analysis . The eradication rates were 97% (61/63) for metronidazole-sensitive strains and 82% (18/22) for metronidazole-resistant strains . CONCLUSIONS: As second-line H . pylori eradication treatment in Japan, rabeprazole-amoxicillin-metronidazole triple therapy is effective, even with metronidazole-resistant strains.

Br J Clin Pharmacol, 2002 Dec, 54(6), 652 - 6
Amoxicillin/clavulanic acid is ineffective at preventing otitis media in children with presumed viral upper respiratory infection: a randomized, double-blind equivalence, placebo-controlled trial; Autret-Leca E et al.; AIMS: To assess the equivalence of amoxicillin/clavulanic acid and placebo in the prevention of acute otitis media in children at high risk of acute otitis media who develop upper respiratory tract infection . METHODS: This was a multicentre, equivalence, randomized, double-blind trial of two parallel groups comparing 5 days of amoxicillin/clavulanic acid 75 mg kg-1 day-1 (i.e . 25 mg kg-1 every 8 h) and placebo . The main outcome measure was acute otitis media occurring within 8-12 days of initiating treatment . RESULTS: Two hundred and three infants, aged 3 months-3 years with upper respiratory tract infection over 36 h and a history of recurrent acute otitis media were included over 8.5 months . Two children were lost to follow-up . Patient characteristics were similar in both groups . In the intention to treat analysis the frequency of acute otitis media was 16.2% (16/99) in the placebo group and 9.6% (10/104) in the amoxicillin/clavulanic acid group (P = 0.288) . The difference between acute otitis media rates was 6.6% (one-sided 95% confidence interval of 14.3%) . The occurrence of side-effects was similar in the amoxicillin/clavulanic acid and placebo groups . CONCLUSIONS: The difference in effectiveness between antibiotic and placebo was not greater than 14.3%, and we calculated that 94 children would need to be exposed to antibiotics to avoid six cases of acute otitis media . In view of the risk of development of resistance due to frequent exposure to antibiotics, our study supports the need for reduction in the administration of antibiotics in upper respiratory tract infection even in children at high risk of acute otitis media.

Am J Gastroenterol, 2002 Dec, 97(12), 3015 - 22
Changing rates of Helicobacter pylori testing and treatment in patients with peptic ulcer disease; Chiorean MV et al.; OBJECTIVES: The aim of this study was to identify temporal trends in the rate of Helicobacter pylori (H . pylori) testing, prevalence, and treatment among patients with peptic ulcer disease in Olmsted County, MN, from 1984 through 1997 . METHODS: All 3317 Olmsted County residents with a clinical diagnosis of peptic ulcer disease at the Mayo Clinic from 1984 through 1997 were identified . The complete medical records of an age-, sex-, and calendar year-stratified random sample were reviewed (n = 720); 298 patients (41%) had confirmed peptic ulcer disease . Changes in proportions of H . pylori testing, infection, and treatment over time were analyzed by logistic regression . RESULTS: Of the 298 patients with confirmed peptic ulcer disease, 32% were tested for H . pylori; 36% were positive for infection, of whom 66% received antibiotic therapy . The rate of testing for H . pylori increased from 0% in 1984 to 96% in 1997, but the prevalence of infection did not change (36.4% vs 36.5%) . The rate of treatment of those infected increased from 0% to 95% . By logistic regression, calendar year was associated with H . pylori testing and treatment but not infection . Recent use of nonsteroidal anti-inflammatory drugs was reported by 58% of patients, and 44% presented with GI bleeding . CONCLUSIONS: Physicians' practice of testing and treating for H . pylori in patients with confirmed peptic ulcer disease has steadily increased over the past 14 yr . However, in our study, only 36% of these patients were infected with H . pylori, whereas the majority used nonsteroidal anti-inflammatory drugs (NSAIDs) . Therefore, testing seems to be more appropriate than empiric treatment in patients with peptic ulcer disease.

Mol Cancer Ther, 2002 Aug, 1(10), 811 - 9
Mitogen-activated protein kinase routes as targets in the action of diaza-anthracene compounds with a potent growth-inhibitory effect on cancer cells; Pipaon C et al.; 1,8-Diaza-anthracene-tetraones are novel intermediates in the synthesis of the antifolate antibiotic diazaquinomycin A that was found before to have potent antitumor activity . Three of them (CV65, CV66, and CV70) were found to inhibit growth of a panel of several human tumor cell lines . The IC50s ranged from 0.05 to 1.5 microM and are comparable with that of doxorubicin . Among the three drugs, CV70 showed the highest cytotoxic activity . The growth-inhibitory action of these compounds was unrelated to the p53 status of the cells . At micromolar concentrations, all three compounds induced apoptosis, CV70 being the most proapoptotic . The incubation of HeLa cells with CV65, CV66, and CV70, at concentrations between 10 and 20 microM, inhibited the activation of c-Jun NH2-terminal kinase by various stimuli and prevented growth factor-induced extracellular signal-regulated kinase (ERK) 5 activation . At least one drug, CV65, also inhibited p38 . This was surprising because proapoptotic antitumor drugs activate stress signaling pathways . Activation of ERK1/ 2 by growth factors or phorbol esters was unaffected by preincubation of cells with CV compounds . In vitro, CV compounds inhibit the enzyme quinone reductase but not c-Jun NH2-terminal kinase or ERK5 . Because doxorubicin also inhibits quinone reductase, we conclude that the inhibitory effect of CV compounds on stress signaling kinases is not a direct effect on the kinases and is likely attributable to upstream elements of the activation cascades.

Zhonghua Nan Ke Xue, 2002, 8(4), 281 - 2
{Interventional therapy for the chronic seminal vesiculitis}; Chen R et al.; OBJECTIVES: To investigate the efficacy of transperineal seminal vesicle puncture under ultrasound guidance and continuous transcatheter antibiotic drugs instillation for the treatment of chronic seminal vesiculitis . METHODS: Forty-two patients with hemospermia were treated from April 1988 to January 2001 . Of them 35 patients with urogenital inflammation were treated by transperineal seminal vesicle puncture under ultrasound guidance and continuous transcatheter antibiotic drugs instillation . RESULTS: Transperineal seminal vesicle puncture and continuous transcatheter antibiotic drugs instillation therapy was adopted for 35 patients with urogenital inflammation and the cure rate was 91.43% . CONCLUSIONS: Transperineal seminal vesicle puncture under ultrasound guidance and continuous transcatheter antibiotic drugs instillation was an effective method for diagnosis and treatment of chronic seminal vesiculitis.

Semin Pediatr Infect Dis, 2002 Oct, 13(4), 280 - 8
Current issues in the diagnosis and management of pediatric empyema; Lewis RA et al.; Empyema is a rare but recognized complication of bacterial pneumonia in children . The incidence of empyema may be rising as vaccination practices and antibiotic prescribing practices promote the emergence of more virulent and resistant organisms . Diagnostic methods vary widely, from thoracentesis to plain radiographs to detailed computed tomography scans . Treatment practices also vary, with some practitioners preferring medical treatment, others employing chest tube drainage or fibrinolytic therapy, and still others aggressively pursuing surgical options . Further study is needed to define the ideal management of empyema . The authors review the current literature and propose an updated management algorithm that incorporates accepted practices as well as emerging trends in diagnosis and management of empyema .

Z Kardiol, 2002 Dec, 91(12), 1053 - 60
{The Lyme carditis as a rare differential diagnosis to an anterior myocardial infarction}; Dernedde S et al.; An acute Lyme carditis affects about 0.3-4% of patients with Lyme borreliosis . The acute period of the disease may be associated with critical atrioventricular conduction abnormalities (complete heart block), supraventricular and ventricular arrhythmias as well a left ventricular failure . Normally, Lyme carditis is completely reversible . Therefore the prognosis largely depends on the management of the acute complications and early antibiotic therapy . Even if the symptoms are spontaneously reversible, antibiotic therapy should be applied to prevent a chronic cardiomyopathy and other manifestations of Lyme borreliosis . We report on a 47-year old patient with acute ECG changes initially suggesting an acute coronary syndrome . However, case history and the erythema migrans indicated an acute Lyme carditis which was confirmed serologically and by myocardial biopsy later.

Nucleic Acids Res, 2002 Dec 15, 30(24), 5425 - 35
In vivo selection of spectinomycin-binding RNAs; Zimmerman JM et al.; The folding of even short RNA molecules in a random library can produce a huge number of possible macromolecular structures . Using this principle, we have designed selections to seek non-coding RNA transcripts capable of interfering with specific macromolecules such as transcription factors in living bacterial cells . Here we show that such selections can uncover an unexpected class of RNAs . In the present case, we report short RNA transcripts whose expression confers bacterial resistance to the antibiotic spectinomycin . We provide evidence that such RNAs cause drug resistance by direct antibiotic binding, demonstrating a class of spectinomycin-specific functional molecular decoys built from RNA.

Toxicol Appl Pharmacol, 2002 Dec 1, 185(2), 85 - 90
Doxorubicin induces an increase of nitric oxide synthesis in rat cardiac cells that is inhibited by iron supplementation; Aldieri E et al.; Doxorubicin is an anthracycline antibiotic generally used in the treatment of solid tumors, but its use is limited by a severe cardiotoxicity, which has been related to the generation of oxygen- and nitrogen-derived free radicals . We have demonstrated that doxorubicin induces nitric oxide (NO) synthesis in the rat cardiac cells H9c2: the drug, after a 24-h incubation, evoked a dose-dependent increase of both NO synthase (NOS) activity in the cells and nitrite levels in the culture supernatant; the accumulation of nitrite (a stable derivative of NO) was prevented by different NOS inhibitors . The increase of NO production was associated with an increased expression of the inducible NOS isoform gene . These effects were significantly inhibited by the coincubation of doxorubicin with iron nitrilotriacetate, a compound that releases iron into the cells . Our results suggest that doxorubicin could induce NO generation in cardiac cells by modifying the iron homeostasis.

Homo, 2002, 53(2), 131 - 45
An assessment of the health status and physical characteristics of an early 20th century community a + Maroelabult in the north west province, South Africa; Steyn M et al.; As a result of mining activities, two related graveyards dating from the last decade of the 19th century and first half of the 20th century had to be relocated . This provided the opportunity to study 47 skeletons of black South Africans, with the aim of obtaining information on the health status and life style of people from a rural area in a mostly pre-antibiotic era . Although the sample is too small to do a proper palaeodemographic analysis, the age spread of the individuals indicates a high infant mortality rate and generally low life expectancy . Medical services were available, as could be seen from the surgically treated forearm fracture of one individual . One individual had signs of a possible treponemal infection, while subperiosteal bone growth on the ribs of another may indicate tuberculosis . High incidences of arthritic disease and joint degeneration probably indicate a high work load . Enlarged fontanelles with delayed closure were noted in some of the infants . Data on long bone lengths also indicate that the growth of the children may have been retarded in comparison to other similarly aged children . It thus seems as though this was a community under considerable stress . A surprising find was the unusually high incidence of individuals with dental abnormalities and variations.

Clin Lab Med, 2002 Dec, 22(4), 911 - 25, vi
Diagnosis of nontuberculous mycobacterial infections; Brown-Elliott BA et al.; This section discusses the methods of laboratory diagnosis of nontuberculous mycobacteria (NTM) using conventional biochemical and nutritional requirements, acid-fast smear microscopy, high performance liquid chromatography (HPLC), antibiotic susceptibility testing, and newer genetic methods such as molecular probes, polymerase chain reaction restriction fragment length polymorphism analysis (PRA), and 16S rDNA sequence analysis . This article discusses how laboratory results are applied by clinicians, and some of the difficulties and controversies regarding the diagnosis of NTM disease after the laboratory work is complete.

Biochim Biophys Acta, 2002 Dec 23, 1567(1-2), 63 - 78
Comparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels; Baginski M et al.; Amphotericin B (AmB) is a very effective anti-fungal polyene macrolide antibiotic whose usage is limited by its toxicity . Lack of a complete understanding of AmB's molecular mechanism has impeded attempts to design less toxic AmB derivatives . The antibiotic is known to interact with sterols present in the cell membrane to form ion channels that disrupt membrane function . The slightly higher affinity of AmB toward ergosterol (dominant sterol in fungal cells) than cholesterol (mammalian sterol) is regarded as the most essential factor on which antifungal chemotherapy is based . To study these differences at the molecular level, two realistic model membrane channels containing molecules of AmB, sterol (cholesterol or ergosterol), phospholipid, and water were studied by molecular dynamics (MD) simulations . Comparative analysis of the simulation data revealed that the sterol type has noticeable effect on the properties of AmB membrane channels . In addition to having a larger size, the AmB channel in the ergosterol-containing membrane has a more pronounced pattern of intermolecular hydrogen bonds . The interaction between the antibiotic and ergosterol is more specific than between the antibiotic and cholesterol . These observed differences suggest that the channel in the ergosterol-containing membrane is more stable and, due to its larger size, would have a higher ion conductance . These observations are in agreement with experiments.

J Laryngol Otol, 2002 Nov, 116(11), 917 - 9
Effectiveness of treatment of tonsillopharyngitis: comparative study; Abdul-Baqi KJ et al.; This study was performed to find out the effectiveness of three different treatments of patients having acute tonsillopharyngitis . Three groups of patients were selected (50 patients in each group) . Group I received one antibiotic according to the result of culture and sensitivity test, while groups II and III received two antibiotics or one antibiotic respectively without a culture and sensitivity test . Diagnosis was based on the acutely subjective symptoms of sore throat and positive clinical examination findings . The effectiveness of treatment in group I (96 per cent) was statistically significant (p<0.05) and higher than group II (82 per cent) and group III (74 per cent), while the difference between group II and III was not statistically significant (p>0.05) . Our findings demonstrate that a culture and sensitivity test of the throat swab is necessary before treating acute tonsillopharyngitis . It was suggested that there should be appropriate selection of antibiotics to preserve normal flora, avoidance antibiotics for viral infections, patient compliance with prescription and educational programmes directed at patients and physicians . All of these measures would assist in reducing the volume of antibiotic use, bacterial resistance and the overall cost of treatment of tonsillopharyngitis.

Transpl Infect Dis, 2002, 4 Suppl 3, 18 - 23
Fungal infection in liver transplantation; Fung JJ; Infection is the common cause of death following transplantation . Fungal infections are associated with high morbidity and mortality, and make up a significant proportion of infectious complications . Unfortunately, the diagnosis is usually made late--symptoms may be mild and non-specific, even with dissemination . Mortality associated with disseminated fungal infections is high, while those associated with limited fungal infections is low . Although the risk factors for invasive fungal infections in liver transplant patients are well identified, early diagnosis is challenging, and commonly used diagnostic methods lack sensitivity and specificity . Although the incidence of fungal infections following liver transplantation appears to be falling, mortality and morbidity associated with fungal infections suggests that future developments should focus on enhancing earlier diagnosis, implementing more effective and less toxic anti-fungal therapies.

Pneumologie, 2002 Dec, 56(12), 793 - 7
{N-acetylcystein in the therapy of chronic bronchitis}; Reichenberger F et al.; Chronic bronchitis (CB) shows an increasing global morbidity and mortality with major impact on socioeconomics . N-Acetylcysteine (NAC), previously used as a mucolytic compound in CB, has also antioxidative effects . Furthermore it influences intrabronchial bacterial colonisation . In a randomised pilot study of 24 patients (16-male, 8 female, mean age 66 +/- 10 years) with acute exacerbation of CB and positive bacterial culture in the sputum, the addition of twice daily 600 mg NAC to standard antibiotic therapy lead to a significantly higher bacterial eradication rate (70 % versus 36 %, p < 0.03) . Clinical studies suggest that treatment with NAC has different effects in CB including a reduction of the number and duration of acute exacerbation episodes and possibly influences lung function . The improvement of symptoms and quality of life also has an impact on socio-economic costs . The use of NAC in CB as an antioxidative rather than a mucolytic compound should be considered . However, further placebo controlled studies are undergoing to definitively establish the role of NAC for the treatment of CB and COPD.

J Ind Microbiol Biotechnol, 2002 Dec, 29(6), 299 - 302
The effect of space flight on the production of actinomycin D by Streptomyces plicatus; Lam KS et al.; The effect of space flight on production of the antibiotic actinomycin D by Streptomyces plicatus WC56452 was examined onboard the US Space Shuttle mission STS-80 . Paired space flight and ground control samples were similarly prepared using identical hardware, media, and inoculum . The cultures were grown in defined and complex media under dark, anaerobic, thermally controlled (20 degrees C) conditions with samples fixed after 7 and 12 days in orbit, and viable residuals maintained through landing at 17 days, 15 h . Postflight analyses indicated that space flight had reduced the colony-forming unit (CFU) per milliliter count of S . plicatus and increased the specific productivity (pg CFU(-1)) of actinomycin D . The antibiotic compound itself was not affected, but its production time course was altered in space . Viable flight samples also maintained their sporulation ability when plated on agar medium postflight, while the residual ground controls did not sporulate.

J Hepatobiliary Pancreat Surg, 2002, 9(4), 429 - 35
Surgical management of severe pancreatitis including sterile necrosis; Hartwig W et al.; BACKGOUNUD/PURPOSE: Severe pancreatitis develops in 15% to 20% of patients with acute pancreatitis, morphologically characterized by extra- and intrapancreatic necrosis and associated with single or multiple organ failure . It is well accepted that surgery is indicated in patients with infected pancreatic necrosis . However, management of sterile necrosis is still controversial . In a prospective study, we evaluated the effect of maximal intensive care unit (ICU) treatment combined with prophylactic antibiotics in patients with necrotizing pancreatitis . METHODS: A total of 306 consecutive patients with acute pancreatitis were hospitalized between November 1993 and August 2001 . All patients with necrotizing pancreatitis diagnosed by computed tomography received ICU treatment, including antibiotics (imipenem/cilastin) . Fine-needle aspiration of pancreatic necrosis was performed in patients with clinical signs of sepsis, and necrosectomy combined with continuous postoperative lavage was indicated when bacterial testing demonstrated infection . In the presence of sterile necrosis, surgery was only performed when there was no clinical improvement despite maximal ICU treatment . RESULTS: Necrotizing pancreatitis was found in 121 patients . Infected necrosis was verified in 41 patients (34%) at a mean of 26 days . Four percent of patients with sterile necrosis and 95% of patients with infected necrosis were operated on . The surgical procedure was successful in 83% of patients as a single intervention; relaparotomy had to be performed in only 7 patients (17%) . Pancreatic abscesses were found in 7 patients; four of these were drained interventionally . The overall mortality of the patients with necrotizing pancreatitis was 9.9% . The mortality of patients with sterile and infected necrosis was 2.5% and 24%, respectively (sterile vs infected; P < 0.01) . CONCLUSIONS: Due to improved intensive care treatment, including prophylactic antibiotics, surgical intervention is usually not indicated in the early course of severe acute pancreatitis . Surgery is clearly indicated in patients with proven infected necrosis . Patients with sterile necrosis should undergo surgery when there is no clinical improvement within 4 weeks of intensive care treatment . In the majority of patients a single intervention is sufficient . Reinterventions are rare and even in patients with abscess formation are not needed, because these can easily be drained interventionally.

J Hepatobiliary Pancreat Surg, 2002, 9(4), 413 - 22
Evidence-based clinical practice guidelines for acute pancreatitis: proposals; Mayumi T et al.; BACKGROUND/PURPOSE: To provide a framework for clinicians to manage acute pancreatitis, evidence-based guidelines have been developed by the Japanese Society of Abdominal Emergency Medicine . METHODS: Evidence was collected by a systematic search of MEDLINE and Japana Centra Revuo Medicina . A total of 1348 papers were reviewed and levels of evidence were assessed . Practical recommendations were also graded . RESULTS: The present guidelines consist of introductions, a summary of recommendations, practice algorithms, definitions, epidemiology, diagnosis, severity assessment, and therapy . The main points of recommendation in these guidelines are: (1) measuring lipase for the diagnosis of acute pancreatitis (recommendation grade {RG}, A) . (2) The Severity of acute pancreatitis should be assessed using a scoring system, such as that of the Japanese Ministry of Health and Welfare or Acute Physiology and Chronic Health Evaluation (APACHE) II (RG, A) . (3) Enhanced computed tomography (CT) should be used for assessment of degree of pancreatic necrosis and inflammation (RG, B) . (4) Prophylactic antibiotic administration should be used for severe pancreatitis (RG, A), but not for mild to moderate pancreatitis (RG, D) . (5) Gabexate mesilate should be used for severe pancreatitis (RG, B) . (6) Enteral feeding should be used for all pancreatitis (RG, B) . (7) Continuous hemodiafiltration and continuous arterial infusion of proteinase inhibitor and antibiotics may be of benefit (RG, C) . (8) Fine-needle aspiration should be done for the diagnosis of infectious pancreatic necrosis, and if positive, necrosectomy is indicated (RG, A) . CONCLUSIONS: These guidelines provide useful information for physicians to manage this troublesome diseasePublication Types:

	Guideline
	Practice Guideline

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