Vet Immunol Immunopathol, 2003 Jul 15, 94(1-2), 11 - 22 Canine leukocyte adhesion deficiency colony for investigation of novel hematopoietic therapies; Creevy KE et al.; The genetic immunodeficiency disease canine leukocyte adhesion deficiency (CLAD) was originally described in juvenile Irish Setters with severe, recurrent bacterial infections . CLAD was subsequently shown to result from a mutation in the leukocyte integrin CD18 subunit which prevents leukocyte surface expression of the CD11/CD18 complex . We describe the development of a mixed-breed CLAD colony with clinical features that closely parallel those described in Irish Setters . We demonstrate that the early identification of CLAD heterozygotes and CLAD-affected dogs by a combination of flow cytometry and DNA sequencing allows the CLAD-affected animals to receive life-saving antibiotic therapy . The distinct clinical phenotype in CLAD, the ability to detect CD18 on the leukocyte surface by flow cytometry, and the history of the canine model in marrow transplantation, enable CLAD to serve as an attractive large-animal model for the investigation of novel hematopoietic stem cell and gene therapy strategies. Eur J Gastroenterol Hepatol, 2003 Jun, 15(6), 621 - 6 Crohn's disease: an immunodeficiency? Folwaczny C, Glas J, Torok HP. Autoimmunity appears to be a key factor in Crohn's disease as it develops in a genetically susceptible host if the immunological tolerance towards bacterial antigens within the gastrointestinal tract is abrogated . The resulting excessive immunological activity leads to a chronic sometimes transmural inflammatory process within the bowel wall . However, several lines of evidence are compatible with an immunodeficiency preceding these processes: humoral or cellular immune defects can predispose to inflammatory bowel disease . An increased bacterial adherence at the intestinal mucosa, which is possibly attributable to impaired expression of defensins was observed in Crohn's disease . Furthermore, the 3020insC mutation of the NOD2/CARD15 gene which is associated with Crohn's disease results in impaired cytokine transcription . Lastly, therapeutic approaches such as the use of antibiotic therapy or granulocyte macrophage colony stimulating factor are in line with the concept of an immunodeficiency being a crucial element in Crohn's disease. J Org Chem, 2003 Jul 11, 68(14), 5575 - 87 Bicyclomycin fluorescent probes: synthesis and biochemical, biophysical, and biological properties; Brogan AP et al.; Bicyclomycin (1) is a commercially available antibiotic whose primary site of action in Escherichia coli is the transcription termination factor rho . Key aspects of the 1.rho interaction-K(d), stoichiometry for 1.rho binding, and whether 1 and ATP binding induce conformational changes in rho-remain unknown . In this study, the design, synthesis, and characterization of a series of bicyclomycin fluorescent probes (BFP) constructed to sense the 1.rho interaction are described and their use documented . We show that dihydrobicyclomycins with medium-to-large C(5a)-substituents afforded excellent inhibitory activities exceeding those of 1 in the poly(C)-dependent ATPase assay . The utility of BFP in bicyclomycin-rho binding studies was documented through the use of 5a-(phenazin-2-ylmethylsulfanyl)dihydrobicyclomycin (15) . Excitation (290 nm) of W381 in wild-type rho in the presence of 15 and ATP led to fluorescence resonance energy transfer (FRET) and gave a K(d) (15) of 9.9 microM . Using ADP in place of ATP or excluding nucleotide did not result in energy transfer, which suggests that ATP binding induced a conformational change in rho . FRET measurements provided an approximate weighted average distance (23 A) between W381 and 15 in the presence of bound ATP . The K(d) value for 15.rho was correlated with ATP binding at the 3 tight ATP binding (K(d)(ATP) = 95 nM) sites in wild-type rho. J Org Chem, 2003 Jul 11, 68(14), 5433 - 8 A new approach for the investigation of isoprenoid biosynthesis featuring pathway switching, deuterium hyperlabeling, and 1H NMR spectroscopy . The reaction mechanism of a novel streptomyces diterpene cyclase; Eguchi T et al.; Recent methodology for the investigation of isoprenoid biosynthesis featuring pathway switching and hyperdeuteration has shown significant advantages in elucidating the reaction mechanism of a novel Streptomyces diterpene cyclase with use of precise atom-level analysis . Insight into the cyclization mechanism involved in the conversion of geranylgeranyl diphosphate (GGPP) into a clerodane hydrocarbon terpentetriene was obtained by heterologous expression in doubly engineered Streptomyces lividans of a diterpene cyclase gene derived from Streptomyces griseolosporeus, a producer of an unique diterpenoid cytotoxic antibiotic terpentecin, and by in vivo labeling with mevalonate-d(9) . The cyclization involved electrophilic protonation, cationic ring closure, Wagner-Meerwein-type rearrangements, and deprotonation . A key feature was that the labeled metabolite as a mixture of predominantly deuterated mosaic molecules provided sufficient information that close analysis of the labeling pattern for each individual isoprene unit was achieved primarily by (1)H NMR spectroscopy . The cyclization of GGPP into the clerodane skeleton catalyzed by the cyclase appears to involve Si-face specific protonation, intermediates with A/B chair-boat conformation, and specific methyl and hydride migrations to give an intermediary C-4 carbocation . Subsequent collapse of the cation through specific removal of the initiating proton and final elimination of diphosphate gives rise to the terpentetriene hydrocarbon. Scand J Infect Dis, 2003, 35(4), 277 - 8 Brucella pelvic tubo-ovarian abscess mimicking a pelvic malignancy; Seoud MA et al.; A 57-y-old woman presented with recurrent abdominal and pelvic pain of 6 months' duration with low-grade fever . A computed tomographic scan indicated an ovarian tumor . Laparotomy revealed a pelvic abscess . Her symptoms resolved following surgery and antibiotic therapy . Pathology revealed an extensive inflammatory process . Tissue culture grew Brucella sp . The diagnosis and management of this previously undescribed pelvic tubo-ovarian abscess present a particular challenge. Mikrobiyol Bul, 2003 Jan, 37(1), 71 - 3 {Thrombocytopenia cases due to acute brucellosis}; Cesur S et al.; The hematological manifestations of brucellosis include anemia, leucopenia, thrombocytopenia and clotting disorders . In this case report, two patients, with clinically and serologically proven brucellosis, manifesting with thrombocytopenia were presented . The first patient who was a 32 years old man, was admitted to the hospital with the complaints of fever, malaise and night sweats . His Brucella agglutination titer was 1/1280 and thrombocyte count was 41.000/mm3 . The second case was a 46 years old man with the complaints of fever and rash . His Brucella agglutination titer was 1/640, thrombocyte count was 38.000/mm3 . Following treatment with doxycycline and rifampisin the thrombocyte counts of the patients returned to normal (respectively, 176.000/mm3 and 162.000/mm3 . The blood cultures of both of these patients did not yield Brucella . The antibiotic therapy of patients discontinued after 6 weeks, with full recovery. Dig Dis, 2003, 21(1), 38 - 45 Modern phase-specific management of acute pancreatitis; Werner J et al.; The management of acute necrotizing pancreatitis has changed significantly over the past years . In contrast to the early surgical intervention of the past, there is now a strong tendency towards a more conservative approach . Initially, severe acute pancreatitis is characterized by the systemic inflammatory response syndrome . Early management is non-surgically and solely supportive . A specific treatment still does not exist . In cases of necrotizing disease, prophylactic antibiotics should be applied to reduce late septic complications . Today, more patients survive the first phase of severe pancreatitis due to improvements of intensive care medicine, thus increasing the risk of later sepsis . Pancreatic infection is the major risk factor with regard to morbidity and mortality in the second phase of severe acute pancreatitis . Whereas early surgery and surgery for sterile necrosis can only be recommended in selected cases, pancreatic infection is a well-accepted indication for surgical treatment in the second phase of the disease . Surgery should ideally be postponed until 4 weeks after the onset of symptoms, as necrosis is well demarcated at that time . Three surgical techniques can be performed with comparable results regarding mortality: necrosectomy combined with the (1) open packing technique, (2) planned staged relaparotomies with repeated lavage, or (3) closed continuous lavage of the retroperitoneum . However, the latter method seems to be associated with the lowest morbidity compared to the other approaches . Schizophr Res, 2003 Aug 1, 62(3), 237 - 44 Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii; Jones-Brando L et al.; The exact mechanisms of action of some antipsychotics and mood stabilizers have not been elucidated . Response to these medications can vary among individuals . Recent studies indicate that infection with the parasite Toxoplasma gondii may contribute to the symptoms of schizophrenia in some individuals . We investigated commonly used antipsychotic and mood stabilizing medications for their ability to inhibit the replication of this organism.We employed a system for testing compounds for in vitro activity against T . gondii . Human fibroblasts (HFF) were treated with test compounds and then exposed to Toxoplasma that has been genetically modified to express cytoplasmic beta-galactosidase . Inhibition by the drugs was determined by spectrophotometric analysis of colorimetric reactions.We tested 12 neuroleptic compounds and found that of these, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro . Valproic acid inhibited the parasite at a concentration below that found in the cerebrospinal fluid and blood of individuals being treated with this medication and displayed synergistic activity with haloperidol and with trimethoprim, an antibiotic commonly used to treat Toxoplasma infections.Several medications used to treat schizophrenia and bipolar disorder have the ability to inhibit the in vitro replication of T . gondii. Eur J Pharm Biopharm, 2003 Jul, 56(1), 121 - 32 Hyperforin a constituent of St John's wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines; Hostanska K et al.; Hyperforin (HP) is an abundant component of St John's wort with antibiotic and antidepressive activity . We report here the ability of HP and that of polyphenolic procyanidin B2 (PB-2) to inhibit the growth of leukemia K562 and U937 cells, brain glioblastoma cells LN229 and normal human astrocytes . HP inhibited the growth of cells in vitro with GI(50) values between 14.9 and 19.9 microM . The growth inhibitory effect of PB-2 was more pronounced in leukemia cell lines K562 and U937, the GI(50) concentrations being about 12.5 microM established after 48 h incubation differed significantly (P<0.05) from those of LN229 and normal human astrocytes (103.1 and 96.7 microM), respectively . Further, HP and hypericin (HY) (a naphthodianthrone from St John's wort) acted synergistically in their inhibitory effect on leukemic (K562, U937) cell growth . Cell death occurred after 24 h treatment with HP and PB-2 by apoptosis . A dose-dependent loss of membrane phospholipid asymmetry associated with apoptosis was induced in all cell lines as evidenced by the externalization of phosphatidylserine (PS) and morphological changes in cell size and granulosity by scatter characteristics . In leukemia U937 cells, HP increased the activity of caspase-9 and caspase-3 and in K562 cells caspase-8 and caspase-3 . In addition, the broad spectrum caspase inhibitor z-VAD-fmk inhibited both the appearance of PS exposure and the activation of caspases, illustrating the functional relevance of caspase activation during HP-induced apoptosis . Cytocidal effects of HP and its cooperation with HY on tumor growth inhibition in a synergistic manner make the St John's wort an interesting option in cancer warranting further in vitro and in vivo investigation. Lancet Infect Dis, 2003 Jul, 3(7), 432 - 42 Fluoroquinolones, tuberculosis, and resistance; Ginsburg AS et al.; Although the fluoroquinolones are presently used to treat tuberculosis primarily in cases involving resistance or intolerance to first-line antituberculosis therapy, these drugs are potential first-line agents and are under study for this indication . However, there is concern about the development of fluoroquinolone resistance in Mycobacterium tuberculosis, particularly when administered as monotherapy or as the only active agent in a failing multidrug regimen . Treatment failures as well as relapses have been documented under such conditions . With increasing numbers of fluoroquinolone prescriptions and the expanded use of these broad-spectrum agents for many infections, the selective pressure of fluoroquinolone use results in the ready emergence of fluoroquinolone resistance in a diversity of organisms, including M tuberculosis . Among M tuberculosis, resistance is emerging and may herald a significant future threat to the long-term clinical utility of fluoroquinolones . Discussion and education regarding appropriate use are necessary to preserve the effectiveness of this antibiotic class against the hazard of growing resistance. Ying Yong Sheng Tai Xue Bao, 2003 Mar, 14(3), 477 - 8 {Formation of blood resin in abiotic Dracaena cochinchinensis inoculated with Fusarium 9568D}; Jiang DF et al.; Fusarium 9568D, which belongs to Fusarium moniliforme, was isolated from the roots of Dracaena cochinchinensis in the suburb of Monglian, Yunnan Province of China . High activities of beta-glucosidase and cellulase were detected in the broth of Fusarium 9568D . The strain was inoculated in abiotic branch and wood of Dracaena cochinchinensis . After 4-5 months of culture, red resin emerged in the inoculated points . UV-IR spectrum analysis and antibiotic assay demonstrated that this resin almost resembled the natural blood resin. Bull Soc Pathol Exot, 2003 May, 96(2), 83 - 5 {Appendicitis and advanced pregnancy . Apropos of 3 cases in the National Hospital of Niamey, Niger}; Harouna YD et al.; Acute appendicitis during pregnancy is uncommon but a serious situation even in developed countries with imaging and laboratories' poor means . Failure to diagnose this disease during advanced pregnancy exposes foetus and mother to serious complications . In this atypical clinical picture associated with non-significant biologic sign only using sonogram can help to early diagnosis . In our developing countries where obstetrical exam was performed by paramedical or general doctor, in doubt the patient must be transferred in medical centre with a capacity of imaging or laboratory exams . Surgical treatment must be undertaken after surgeon, obstetrician, and other physicians's consultation . Antibiotic and tocolytic treatments are urgent . In this study, all babies were lost by premature labour occurred after surgery. Nucleic Acids Res Suppl, 2001, (1), 31 - 2 Stereoselective synthesis of 1'-C-carbon-subsituted 4'-thionucleosides from 4-thiofuranoid glycal; Haraguchi K et al.; PhSeCl or NIS-initiated glycosylation to 2-5, which were prepared through lithiation of 4-thiofuranoid glycal 1, proceeded stereoselectively to give the target 1'-C-carbon-substituted 4'-thiopyrimidine nucleosides . This synthetic method enabled us to synthesize 4'-thioanalogue 13 of nucleoside antibiotic angustmycin. Biophys Chem, 2003 May 1, 104(1), 239 - 48 Electrochemical determination of interaction parameters for DNA and mitoxantrone in an irreversible redox process; Wang S et al.; Mitoxantrone (MXT), an anti-tumor antibiotic, shows irreversible electrochemical behavior at a waxed graphite electrode in a 0.05 M Tris-HCl buffer (pH 7.4) solution . The interaction between MXT and calf thymus DNA (ctDNA) in solution has been studied using cyclic voltammetry . An electrochemical equation suitable for examining the binding of irreversibly electroactive molecules to DNA is established . Determination of diffusion coefficients of both free and binding MXT (D(f), D(b)), the binding constant (K) and binding site size (s base pairs per molecule, bp) of MXT with DNA was performed on the basis of the equation . A nonlinear fit analysis of the experimental data yielded: D(f)=3.76 x 10(-5) cm(2)s(-1), D(b)=2.73 x 10(-7) cm(2)s(-1), K=8.7 x 10(9) cm(3)mol(-1), s=2.8 bp . The results demonstrate that MXT binds tightly to ctDNA and covers three base pairs . The anthraquinone of MXT, which is a planar heterocyclic ring, intercalates between the DNA's base pairs . The two aminoethylamino side-chains of the drug fit to the major groove reinforce the combination of MXT and DNA . The results show that MXT is a DNA intercalator with a high binding constant compared to those of other anthraquinones. Am J Ophthalmol, 2003 Jul, 136(1), 203 - 4 Facial necrotizing fasciitis following acute dacryocystitis; Lin PW et al.; PURPOSE: To report a case of progressive necrotizing fasciitis of the face following acute dacryocystitis . DESIGN: Interventional case report . METHODS: A 60-year-old woman presented with left acute dacryocystitis with abscess formation that had ruptured; a small wound remained . Erythematous swelling of the left eyelid and face developed 3 days later . Clinical progression and computed tomographic findings led to the diagnosis of necrotizing fasciitis with abscess formation . Early intravenous antibiotics and repeated surgical debridements were performed . RESULTS:Soft tissue necrosis was found the fascial planes extending deep to the maxilla bone and periorbital fat . The patient was successfully treated without ocular, orbital, or facial complications . CONCLUSIONS: Necrotizing fasciitis of the eyelid and face progresses rapidly . Early diagnosis, prompt intravenous antibiotic administration, and aggressive surgical debridement will prevent the associated morbidity and mortality. Swiss Med Wkly, 2003 May 3, 133(17-18), 247 - 57 Acute exacerbations of COPD; MacNee W; Acute exacerbations of COPD (AECOPD) are a common cause of morbidity and mortality . There is a need for a standardised definition of an exacerbation of COPD . The common aetiological factors are bacterial, viral infection and air pollutants . Exacerbations of COPD may adversely affect the natural history of COPD . Several strategies are available now to prevent or reduce exacerbations of COPD including immunisation against influenza and inhaled corticosteroids in patients with moderate/severe disease . The mainstay of treatment involves increasing bronchodilator therapy, systemic glucocorticoids which have now been shown to have a beneficial effect . The circumstances for the use of antibiotic therapy is now established in patients with increased breathlessness, increased sputum production and/or sputum purulence . In those with respiratory failure, noninvasive ventilation has been shown to reduce intubation rates, shorten lengths of hospitalisation, and improve mortality . Early or immediate supported discharge for selected patients has been shown to be effective in the management of patients with COPD. Plast Reconstr Surg, 2003 Jul, 112(1), 282 - 7 Postrhinoplasty nasal cysts and the use of petroleum-based ointments and nasal packing; Liu ES et al.; Nasal cysts are rare complications of rhinoplasty, and numerous theories exist regarding their cause . The term "paraffinoma" has been used to describe cyst formation observed after topical antibiotic ointment application with nasal packing in the immediate postoperative period . Such complications are rare but may occur because of the inherent properties of the agent used or a lack of meticulous technique (in the placement of incisions and nasal packing) . Three cases of postrhinoplasty cysts with a variety of presentations, including incidental intraoperative findings, bilateral medial canthal masses, and a draining dorsal cyst, are described . Although such cysts are uncommon, techniques to prevent these unwanted sequelae should routinely be used, with the judicious application of non-petroleum-based topical antibiotic preparations. J Nephrol, 2003 May-Jun, 16(3), 379 - 83 Rapid diagnosis of peritonitis in peritoneal dialysis patients; Cropper E et al.; BACKGROUND: Peritonitis is the major complication of peritoneal dialysis (PD) and has acute morbidity and resources implications . Episodes of peritonitis are associated with higher risk of peritoneal membrane failure . Rapid diagnosis of peritonitis would allow early antibiotic commencement with potential benefits of reduced need for in-patient care and dialysis modality change . This study examined the utility of a rapid peritonitis diagnosis method (Periscreen) . METHODS: This was a prospective study in a single unit and included all PD patients presenting with symptoms or signs of peritonitis over 12 months . In each clinical circumstance in which the diagnosis or exclusion of peritonitis was required and in follow-up peritonitis cases, PD fluid was sent for standard laboratory analysis but also tested using the Periscreen strip . The relationship between this rapid diagnostic strip and standard laboratory methods for determination of PD fluid neutrophil count was determined . RESULTS: This study found the Periscreen strip easy to use and interpret . All 17 episodes of peritonitis (defined by ISPD criteria) were detected and results of the strip correlated closely with the laboratory cell count . In this study sensitivity of the Periscreen was 100% and specificity was 98%, positive predictive value was 95.6% and negative predictive value was 100% . Results were equally good in glucose containing fluids and icodextrin . CONCLUSIONS: Periscreen is a sensitive, specific rapid tool for the presumptive diagnosis of peritonitis in PD patients used at the "point of care" . Results correlated with the laboratory white cell count, a test that takes longer to perform . Widespread use in PD would aid in the early recognition and treatment of peritonitis. Thorax, 2003 Jul, 58(7), 589 - 93 Time course of recovery of health status following an infective exacerbation of chronic bronchitis; Spencer S et al.; BACKGROUND: The magnitude and time course of effect of an acute exacerbation of chronic bronchitis (AECB) on health status are not known . Data from the GLOBE study, a randomised double blind trial of antibiotic therapy, were used to investigate these effects . METHODS: 438 patients with AECB received either gemifloxacin 320 mg once daily for 5 days (214 patients) or clarithromycin 500 mg twice daily for 7 days (224 patients) and were followed up for 26 weeks . St George's Respiratory Questionnaire (SGRQ) scores were obtained at baseline and after 4, 12, and 26 weeks . RESULTS: At presentation during an exacerbation SGRQ scores were worse (Total score difference 5.4 units, 95% CI 1.9 to 8.8, p=0.002) in patients who had a subsequent exacerbation during follow up . The greatest improvement in SGRQ score occurred within the first 4 weeks (mean 8.9 units, 95% CI 6.5 to 11.5, p<0.0001) . Subsequently, scores improved more rapidly in patients with no further exacerbations . At 26 weeks the difference between the two groups was 9.6 units (95% CI 5.7 to 13.4, p<0.0001) . In patients with no further exacerbations the SGRQ score improved between 4 and 12 weeks by a further 4.1 units (95% CI 2.2 to 5.9, p<0.0001) . CONCLUSIONS: A single infective AECB has a sustained effect on health status . The recovery period is long even in patients who have no further exacerbations . A second episode within 6 months limits recovery markedly . Treatments that reduce exacerbation frequency could have a significant impact on health status. J Pharm Pharmacol, 2003 May, 55(5), 653 - 60 Two lead drug designs based on chloramphenicol as the parent structure, which express alkylation activity with potential for clinical applications; Bartzatt R; Chloramphenicol is a bacteriostatic antibiotic which acts primarily as an inhibitor of bacterial protein synthesis . Modification of chloramphenicol structure was accomplished by replacing the two hydroxyl groups (-OH) with a chlorine atom for LEAD-1 or a chloroethyl ether group (-OCH(2)CH(2)Cl) for LEAD-2 . The resulting daughter compounds expressed significant alkylating activity at physiological temperature of 37 degrees C and at pH 7.4 . Alkylation activity was evaluated after reaction with guanosine 5'-diphosphate (GDP), L-serine, L-glutamic acid, and p-chloroaniline . The partition coefficient (log P) was determined for chloramphenicol, LEAD-1 and LEAD-2 to be 0.854, 3.409 and 3.10, respectively . The molecular dipole of chloramphenicol, LEAD-1 and LEAD-2 was calculated to be 5.804, 3.961 and 4.097 Debye, respectively . All three structures showed zero violations of the Rule of 5, which indicates good bioavailability . Values for polar surface area (TPSA) indicate an intestinal absorption of 51% and 35% for LEAD-1 and LEAD-2, respectively . The reduction to only one proton donor in LEAD-1 and LEAD-2 structures (chloramphenicol having three proton donors) indicates an improvement of membrane penetration compared to chloramphenicol . (13)C NMR analysis of molecular structures was accomplished and fast atom bombardment mass spectrometry analysis of a reaction mixture showed LEAD-1 alkylation of guanosine 5'-diphosphate. Arch Esp Urol, 2003 May, 56(4), 434 - 6 {Necrosis of the penis in a diabetic patient: presentation of a case}; Lopez Pacios JC et al.; OBJECTIVES: To present a short review of the diagnosis, clinical features, and treatment of male genitalia necrosis under the format of a case report . METHODS: We review the case of a diabetic patient without good blood sugar control who suffered from various diabetic complications diagnosed and treated at our hospital of a penile necrosis . We perform a bibliographic review about male genitalia necrosis regarding its etiology, diagnosis and treatment . RESULTS: Male genitalia necrosis is a rare disease but it is associated with high morbidity and mortality . The present case was diagnosed at the emergency room at our Hospital . Conservative treatment with antibiotic therapy and corticosteroid ointments was undertaken successfully . CONCLUSIONS: To perform an etiologic evaluation of the necrosis (dry or infectious) is important to select the right treatment . The high mortality of these diseases requires a precise and early diagnosis, since this influences the good or bad evolution of the disease. Clin Infect Dis, 2003 Jul 1, 37(1), e8 - 11 Epub 2003 Jun 25. Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients; Hachem RY et al.; We report 2 cases of serotonin syndrome and myelosuppression in bone marrow transplant recipients who received linezolid in combination with a selective serotonin reuptake inhibitor (SSRI) . Given the risks to patients in this high-risk group, we recommend that this combination of medications be avoided if alternative antibiotic therapy is possible . If no alternative therapy is possible, prescribers should discontinue SSRI therapy and monitor these patients closely for evidence of serotonin syndrome or the development of hematological toxicity. Br J Nurs, 2003 Jun 12-25, 12(11), 682 - 5 Principles for the correct administration of medicines: 1; Dimond B; Heather was drawing up antibiotics which were to be given intravenously to a patient suffering from a severe chest infection . She had to mix the antibiotic with a saline solution and then administer it to the patient . She had a lot of patients to care for and failed to notice that the expiry date on the antibiotic had passed . The patient subsequently suffered harm . Is Heather to blame? Eur J Cardiothorac Surg, 2003 Jun, 23(6), 996 - 1000; discussion 1000-1 Reoperation after fresh homograft replacement: 23 years' experience with 655 patients; Sadowski J et al.; OBJECTIVE: Through a retrospective study on the use of fresh homografts in 655 aortic valve replacement patients over a period of 23 years, we aimed to assess the reasons for eventual reoperation and causes of valve dysfunction . METHODS: Between January 1980 and December 2002, 655 patients received fresh homografts . All homografts were antibiotic sterilized and stored at 4 degrees C . During this time, 139 patients (116 male and 23 female) with a mean age of 46.7 years (range 18-72) required reoperation . RESULTS: The 30-day hospital overall mortality was 2.87% . The mean durability for all homografts was 12.4+/-4.54 years (1 month to 23 years) . The cumulative rates for freedom from reoperation for any cause were 94.09+/-2% at 5 years and 87.9%+/-4% at 10 years, 76.6 at 15 years, 49.55 at 20 years . The major cause of valve dysfunction and indication for reoperation was degeneration in 111 patients (79.8%) . Predominant aortic valve insufficiency in 87 patients (62.5%) and predominant stenosis in 24 patients (17.26%) . Endocarditis occurred in 21 patients (15.1%) . Early endocarditis was diagnosed in five patients (3.59%), late endocarditis in 16 patients (11.5%) . Additional causes for reoperation included ascending aortic aneurysm, mitral valve insufficiency and congestive cardiomyopathy . Seventeen patients (12.2%) required concomitant procedures . Coronary artery bypass grafting was performed in six cases (4.3%), mitral valve replacement in five cases (3.59%), mitral valve annuloplasty in six (4.3%) . The primary reoperative procedure was artificial/mechanical aortic valve implantation . In five cases, St . Jude Medical conduit grafts were implanted due to ascending aortic aneurysms . Homograft reimplantation was performed in four cases . One patient underwent mitral valve replacement and one patient received a heart transplant . CONCLUSION: The results of the study suggest that reoperation in patients with aortic homografts is a low-risk procedure as compared to alternative therapies . Primary allograft aortic valve replacement can give acceptable results for up to 23 years . The major cause of valve dysfunction and indication for reoperation was degeneration . Cumulative rates for freedom from reoperation for any cause in age groups suggest careful selection and indications in homograft implantation in the younger patients . Young age is a risk factor for an early homograft structural deterioration (degeneration). Eur J Cardiothorac Surg, 2003 Jun, 23(6), 943 - 9 Risk factors for sternal wound infection and mid-term survival following coronary artery bypass surgery; Lu JC et al.; OBJECTIVE: To identify risk factors for sternal wound infection following coronary artery bypass surgery (CABG), and to compare early and mid-term survival outcome . METHODS: Data were prospectively collected for 4228 patients who underwent CABG surgery between April 1997 and March 2001 . One hundred and nine (2.6%) patients developed sternal wound infection . We used logistic regression to identify independent risk factors associated with post-operative sternal wound infection . Patient records were linked to the National Strategic Tracing Service, which records all deaths in the UK, to establish current vital status . Deaths occurring over time were described using Kaplan-Meier techniques . To control for differences in patient characteristics, we used Cox proportional hazards analysis to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI) . RESULTS: The results of the logistic regression analysis found that the independent predictors of sternal wound infection were obesity (odds ratio (OR) 2.0; P<0.001), New York Heart Association class >/=3 (OR 1.6; P=0.022), use of bilateral internal mammary arteries (OR 3.2; P<0.001), increasing number of grafts (OR 1.5; P<0.001), re-exploration for bleeding (OR 3.1; P=0.011), and increased duration of mechanical ventilation (for every 10 h (OR 1.12; P<0.001)) . Three hundred and forty one (8.1%) deaths occurred during the study period with mean follow up of 3.2+/-1.3 years . The crude HR of mid-term mortality for sternal wound infection patients was 2.51 (95% CI 1.59-3.94, P<0.001) . After adjustment for pre, intra and post-operative factors, the adjusted HR of mid-term mortality for sternal wound infection patients was 1.64 (95% CI 1.03-2.61, P=0.037) . The adjusted freedom from death for sternal wound infections at 30 days, and 1, 2 and 4 years was 96.8, 93.7, 91.4 and 86.7%, respectively, compared with 98.1, 96.1, 94.7 and 91.7% for patients without sternal wound infections . CONCLUSIONS: In conclusion, we have identified risk factors for sternal wound infection, many of which are modifiable . We have also shown that there is a significant increase in mortality in patients with sternal wound infection during a 4-year follow-up period after CABG. Mol Microbiol, 2003 Jul, 49(2), 309 - 18 The avilamycin resistance determinants AviRa and AviRb methylate 23S rRNA at the guanosine 2535 base and the uridine 2479 ribose; Treede I et al.; Avilamycin is an orthosomycin antibiotic that has shown considerable potential for clinical use, although it is presently used as a growth promoter in animal feed . Avilamycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit . The ribosomes of the producer strain, Streptomyces viridochromogenes Tu57, are protected from the drug by the action of three resistance factors located in the avilamycin biosynthetic gene cluster . Two of the resistance factors, aviRa and aviRb, encode rRNA methyltransferases that specifically target 23S rRNA . Recombinant AviRa and AviRb proteins retain their activity after purification, and both specifically methylate in vitro transcripts of 23S rRNA domain V . Reverse transcriptase primer extension indicated that AviRa is an N-methyltransferase that targets G2535 within helix 91 of the rRNA, whereas AviRb modified the 2'-O-ribose position of nucleotide U2479 within helix 89 . MALDI mass spectrometry confirmed the exact positions of each of these modifications, and additionally established that a single methyl group is added at each nucleotide . Neither of these two nucleotides have previously been described as a target for enzymatic methylation . Molecular models of the 50S subunit crystal structure show that the N-1 of the G2535 base and the 2'-hydroxyl of U2479 are separated by approximately 10 A, a distance that can be spanned by avilamycin . In addition to defining new resistance mechanisms, these data refine our understanding of the probable ribosome contacts made by orthosomycins and of how these antibiotics inhibit protein synthesis. Rev Iberoam Micol, 2002 Jun, 19(2), 99 - 103 Antagonistic activity of Penicillium oxalicum Corrie and Thom, Penicillium decumbens Thom and Trichoderma harzianum Rifai isolates against fungi, bacteria and insects in vitro; Santamarina MP et al.; The antibiotic activity of 70 isolates belonging to the genera Aspergillus, Penicillium, Fusarium, Alternaria and Trichoderma was tested as preliminary screening . The highest activity was obtained with three Penicillium oxalicum isolates, one Penicillium decumbens isolate and the Trichoderma harzianum isolate . After that, we chose these five isolates in order to carry out other studies with bacteria, fungi and insects . Extracts from these isolates were obtained . The extracts were tested for antibiotic activity with positive results, which implies that metabolite production is involved in this antagonistic effect . The highest activity was shown by T . harzianum and P . oxalicum extracts, but there was high variability among P . oxalicum isolates. J Nat Prod, 2003 Jun, 66(6), 888 - 90 Ainigmaptilones, sesquiterpenes from the Antarctic gorgonian coral Ainigmaptilon antarcticus; Iken KB et al.; Antarctic octocorals from the Weddell Sea of Western Antarctica appear to select either physical or chemical means of defense . Fractionation of the bioactive extract from the chemically defended Antarctic gorgonian coral Ainigmaptilon antarcticus yielded two sesquiterpenes, ainigmaptilones A (1) and B (2) . Ainigmaptilone A has broad spectrum bioactivity toward sympatric predatory and fouling organisms, including antibiotic activity. J Am Acad Orthop Surg, 2003 May-Jun, 11(3), 212 - 9 Open fractures: evaluation and management; Zalavras CG et al.; Open fractures are complex injuries that involve both the bone and surrounding soft tissues . Management goals are prevention of infection, union of the fracture, and restoration of function . Achievement of these goals requires a careful approach based on detailed assessment of the patient and injury . The classification of open fractures is based on type of fracture, associated soft-tissue injury, and bacterial contamination present . Tetanus prophylaxis and intravenous antibiotics should be administered immediately . Local antibiotic administration is a useful adjunct . The open fracture wound should be thoroughly irrigated and debrided, although the optimal method of irrigation remains uncertain . Controversy also exists regarding the optimal timing and technique of wound closure . Extensive soft-tissue damage may necessitate the use of local or free muscle flaps . Techniques of fracture stabilization depend on the anatomic location of the fracture and characteristics of the injury. Knee Surg Sports Traumatol Arthrosc, 2003 Jul, 11(4), 219 - 22 Epub 2003 Jun 19. Positive culture in allograft ACL-reconstruction: what to do? Diaz-de-Rada P, Barriga A, Barroso JL, Garcia-Barrecheguren E, Alfonso M, Valenti JR. The transmission of disease or infection from the donor to the recipient is always a risk with the use of allografts . We carried out a research study on the behavioural pattern of implanted allografts, which were initially stored in perfect conditions (all cultures being negative) but later presented positive cultures at the implantation stage . Because there is no information available on how to deal with this type of situation, our aim was to set guidelines on the course of action which would be required in such a case . We conducted a retrospective study of 181 patients who underwent an ACL reconstruction using BPTB allografts . All previous bone and blood cultures and tests for hepatitis B and C, syphilis and HIV were negative . An allograft sample was taken for culture in the operating theatre just before its implantation . The results of the cultures were obtained 3-5 days after the operation . We had 24 allografts with positive culture (13.25%) after the implantation with no clinical infection in any of these patients . Positive cultures could be caused by undetected contamination while harvesting, storing or during manipulation before implantation . The lack of clinical signs of infection during the follow-up of our patients may indicate that no specific treatment-other than an antibiotic protocol-would be required when facing a case of positive culture of a graft piece after its implantation. Cornea, 2003 Jul, 22(5), 468 - 72 In vitro toxicity of netilmicin and ofloxacin on corneal epithelial cells; Scuderi AC et al.; PURPOSE: To evaluate the in vitro cytotoxic effect of the aminoglycoside antibiotic netilmicin on rabbit corneal epithelial cells (SIRC) compared with ofloxacin, a commonly used fluoroquinolone ocular antibiotic . METHODS: SIRC cell cultures were incubated for 8 to 72 h in the presence and absence of netilmicin (1.5, 3, and 6 mg/mL) and equal concentrations of ofloxacin . Cell viability in treated and untreated SIRC cells was measured by both neutral red and MTT colorimetric assays at 8, 24, and 72 h, whereas changes in cell morphology were examined at 8, 24, 48, and 72 hours by the use of phase-contrast microscopy . RESULTS: Netilmicin, at all tested concentrations, failed to alter SIRC cell viability or morphology . In contrast, all concentrations of ofloxacin caused statistically significant dose- and time-dependent reductions in cell viability even after 8 h . After 72 h there was complete loss of cell viability . Morphologic examination of SIRC cells after 8 h of incubation with ofloxacin revealed that the fluoroquinolone antibiotic, at all concentrations, produced large numbers of dead cells, compromised intercellular contacts, and altered general morphology . After 48 h the cell monolayer was observed to be completely destroyed . CONCLUSION: Netilmicin, at the concentrations used, is an antibiotic devoid of obvious cellular toxicity and may also be considered as a suitable first-choice drug in the treatment of those pathologies that compromise the integrity of the ocular surface. Transplant Proc, 2003 Jun, 35(4), 1565 - 6 Relapsing encephalopathy following small bowel transplantation; Shah SM et al.; We report a case of a 40-year-old man presenting with relapsing encephalopathy 4 years post-intestinal transplantation . Each episode was preceded by symptoms suggestive of subacute intestinal obstruction, marked dehydration, and, on one occasion, grade 4 encephalopathy . Physical examination revealed hypertonia, clonus, and hyperreflexia . Biochemistry was consistent with renal impairment, metabolic alkalosis, hyperammonaemia, and normal liver function . Plain radiographs and abdominal computed tomography revealed dilated proximal small bowel loops, and barium radiography demonstrated a strictured distal anastomosis . Hydrogen breath testing indicated bacterial overgrowth . Following rehydration and antibiotic therapy, the patient recovered fully between episodes . Further episodes of encephalopathy did not recur following resection of the distal anastomotic stricture and resolution of bacterial overgrowth . Unfortunately, one year later the patient died of pneumonia . To the best of our knowledge, encephalopathy secondary to intestinal transplant related porto-caval shunt and bacterial overgrowth in strictured bowel has not been previously reported but might have implications for the management of future patients. Rev Iberoam Micol, 2002 Sep, 19(3), 144 - 8 New strategies for treatment of Candida vaginal infections; Magliani W et al.; New strategies for treatment of vaginal candidiasis have been recently exploited, due to widespread occurrence of this disease, in particular as recurrent infections, limitations of safe and efficacious antifungals as well as the lack of reliable preventative approaches . In this review new chemotherapeutic and immunotherapeutic strategies, based on the improved understanding of the immunopathogenesis of this prevalent human infection, will be discussed . The role of killer antibodies (or their molecular derivatives), i.e . antibodies that show antibiotic activity bearing the internal image of a yeast killer toxin (KT), characterized by a wide spectrum of microbicidal activity, and of the specific cell wall KT receptor as putative new therapeutic agents and preventative or therapeutic vaccines, respectively, will be particularly outlined. Epidemiol Infect, 2003 Jun, 130(3), 443 - 51 Prevalence of gastroenteritis among 4-year-old children in South Australia; Heyworth JS et al.; The aim of this study was to determine the prevalence of gastroenteritis among children aged 4 years in South Australia . A cross-sectional survey of 9543 South Australian children aged 4 years was undertaken . Parents completed a questionnaire on behalf of their child who had attended a pre-school health check in 1998 . The questionnaire covered gastrointestinal and respiratory symptoms experienced by the child in the previous 2 weeks and other risk factors for gastroenteritis . The 2-week prevalence of gastroenteritis among 4-year-old children was 14.2% . The major risk factors for gastroenteritis were presence of persons who had gastroenteritis inside the home, contact with persons who had gastroenteritis outside the home, antibiotic use and sore throat . Medical attention was sought for 20% of children who had gastroenteritis . Gastroenteritis is a significant cause of morbidity among young children and presents a considerable burden on the community . A substantial proportion of these occurrences of highly credible gastrointestinal symptoms may be manifestations of respiratory infections. Prescrire Int, 2003 Jun, 12(65), 85 - 8 Oseltamivir: new preparation . An antiviral agent with little impact on influenza; Rhinosinusitis; Division of Otolaryngology-Head and Neck Surgery, University of Louisville School of Medicine, Myers Hall, 129 East Broadway Street, Louisville, KY 40292, USA . welby@insightbb.com Rhinosinusitis is one of the most common health care complaints in this country . The burden on affected individuals in terms of decreased productivity, absenteeism from the workplace, and diminished quality of life, when added to the cost of care and the growing public health menace of antibiotic-resistant bacteria, makes rhinosinusitis a serious disease that warrants precise diagnosis and effective therapy . Technologic innovations in endoscopy and imaging have improved understanding of sinus pathophysiology, but diagnosis remains clinical and treatment empiric . Recognized pitfalls in acute rhinosinusitis management are injudicious use of antibiotics and antihistamines . Chronic rhinosinusitis is a complex, multifactorial disorder, not simply an infectious disease . In many patients, noninfectious inflammation and structural problems play an important role . Medical management should include an intranasal corticosteroid in addition to an appropriate antibiotic . Otolaryngology referral is indicated for complications of acute infection, immunocompromised patients, nasal polyps, and chronic rhinosinusitis having substantial effect on quality of life . Modern surgical principles that focus on obstructive pathology in the OMC region are efficacious but rarely curative . Developments in the fields of immunology, molecular biology, and genetics will lead to more effective treatment options. ORL J Otorhinolaryngol Relat Spec, 2003 Mar-Apr, 65(2), 106 - 16 A systematic review of the effectiveness of ofloxaxin otic solution for the treatment of suppurative otitis media; Abes G et al.; The objectives of the study were to determine the effectiveness and incidence of adverse events of ofloxacin otic solution for suppurative otitis media compared with other treatments . All randomized controlled trials and nonrandomized comparative clinical trials published from 1966 to 2000 using ofloxacin otic solution as one of the interventions were reviewed and data were extracted and analyzed . Eleven clinical trials (9 randomized and 2 nonrandomized) enrolling 1,484 adults and children were finally included in the analysis . Five studies employed clear concealment procedure in the allocation of treatment whereas evaluation of outcome was at least single-blinded in 6 trials . The probability of overall cure rate was higher with 0.3% ofloxacin otic solution than with other topical or systemic antibiotics in 9 of the studies analyzed (OR = 2.67; 95% CI = 2.04, 3.50) . Resolution of secondary outcome parameters evaluated at least 1 week after treatment was higher with 0.3% ofloxacin otic solution: resolution of otalgia (4 trials; OR = 2.41; 95% CI = 1.2, 4.82); resolution of otorrhea (11 trials; OR = 2.78; 95% CI = 2.12, 3.65), and bacterial eradication rate (6 trials; OR = 3.86; 95% CI = 2.54, 5.87) . A subgroup analysis of 4 studies comparing ofloxacin otic solution with antibiotic- and steroid-containing otic solution showed a higher cure rate for ofloxacin otic solution (OR = 2.73; 95% CI = 1.52, 4.90) . Another subgroup analysis on 3 studies comparing ofloxacin otic solution with oral systemic antibiotics showed higher resolution of otorrhea with ofloxacin otic solution (OR = 2.78; 95% CI = 2.12, 3.65) . Of 4 studies with data on adverse events, the probability of adverse events was lower with ofloxacin otic solution than with other topical antibiotics (OR = 0.28; 95% CI = 0.19, 0.42) . Subgroup analysis showed that 0.3% ofloxacin otic solution showed better results in terms of overall cure rate, resolution of otorrhea, otalgia, bacterial eradication rate and incidence of adverse events . Whether due to chronic suppurative otitis media (CSOM) or draining tympanostomy tube, the overall cure rate (CSOM OR = 4.86; with tympanostomy tube OR = 2.13) and resolution of otorrhea (CSOM OR = 4.42; with tympanostomy tube OR = 1.66) were likewise in favor of 0.3% ofloxacin otic solution . The studies included in this meta-analysis showed generally homogenous results in all clinical and laboratory outcomes analyzed, except for the evaluation of adverse events . The authors conclude that 0.3% ofloxacin otic solution is better than other otic antibiotic drops and other oral antibiotics in terms of overall cure rate and resolution of secondary outcome parameters . Estimates on the beneficial effects of ofloxacin otic solution are limited to the period of study included in this review . Arch Intern Med, 2003 Jun 23, 163(12), 1409 - 16 Effects of computerized physician order entry and clinical decision support systems on medication safety: a systematic review; Kaushal R et al.; BACKGROUND: Iatrogenic injuries related to medications are common, costly, and clinically significant . Computerized physician order entry (CPOE) and clinical decision support systems (CDSSs) may reduce medication error rates . METHODS: We identified trials that evaluated the effects of CPOE and CDSSs on medication safety by electronically searching MEDLINE and the Cochrane Library and by manually searching the bibliographies of retrieved articles . Studies were included for systematic review if the design was a randomized controlled trial, a nonrandomized controlled trial, or an observational study with controls and if the measured outcomes were clinical (eg, adverse drug events) or surrogate (eg, medication errors) markers . Two reviewers extracted all the data . Discussion resolved any disagreements . RESULTS: Five trials assessing CPOE and 7 assessing isolated CDSSs met the criteria . Of the CPOE studies, 2 demonstrated a marked decrease in the serious medication error rate, 1 an improvement in corollary orders, 1 an improvement in 5 prescribing behaviors, and 1 an improvement in nephrotoxic drug dose and frequency . Of the 7 studies evaluating isolated CDSSs, 3 demonstrated statistically significant improvements in antibiotic-associated medication errors or adverse drug events and 1 an improvement in theophylline-associated medication errors . The remaining 3 studies had nonsignificant results . CONCLUSIONS: Use of CPOE and isolated CDSSs can substantially reduce medication error rates, but most studies have not been powered to detect differences in adverse drug events and have evaluated a small number of "homegrown" systems . Research is needed to evaluate commercial systems, to compare the various applications, to identify key components of applications, and to identify factors related to successful implementation of these systems. Dis Esophagus, 2003, 16(2), 66 - 9 Clinical findings and risk factors for Candida esophagitis in outpatients; Underwood JA et al.; We retrospectively reviewed 18 patients with endoscopically discovered Candida esophagitis to more fully characterize this entity and identify predisposing conditions . Candida esophagitis was defined by the presence of fungal mycelia on brush cytology . Only two patients had an associated malignancy . Other possible predisposing risk factors were acid suppressive therapy (14 patients), prior gastric surgery (five), mucosal barrier injury (four), inhaled steroid use (four), oral steroid use (three), esophageal motility disorders (three), rheumatologic disorders (three), prior antibiotic use (two) and diabetes mellitus (two) . The majority of patients had more than one proposed risk factor . Ten (56%) were treated with antifungal therapy . Thus, Candida esophagitis was infrequently seen in patients with associated malignancy . Prospective evaluation of predisposing conditions and treatment is recommended. Nihon Kokyuki Gakkai Zasshi, 2003 May, 41(5), 365 - 9 {A case of septic pulmonary embolism accompanied with tricuspid valve endocarditis and pyogenic spondylitis}; Hanibuchi M et al.; A 54-year-old man was admitted with complaints of high fever and lumbago . A chest radiograph on admission showed bilateral multiple patchy infiltrations . Chest CT showed multiple nodules of various sizes, some with necrotic centers and feeding vessels in the peripheral areas . Some nodules had wedge-shaped consolidations aboutting the pleura . Echocardiography showed vegetation about 12 x 7 mm in size attached to the tricuspid valve . MR imaging of the lumbar vertebrae showed increased signal intensity in the vertebral bodies in L1-4 in T2-weighted images and a further increase of signal intensity by gadolinium enhancement in T1-weighted images . These findings led to a diagnosis of septic pulmonary embolism accompanied with tricuspid valve endocarditis and pyogenic spondylitis irrespective of a negative blood culture . The fever was reduced and the inflammatory findings and chest radiographs were improved by antibiotic therapy, and then tricuspid valvuloplasty was performed . The characteristic CT features of septic pulmonary embolism, mentioned above, can contribute to an accurate and early diagnosis and proper treatment. MMW Fortschr Med, 2003 May 15, 145(20), 33 - 7 {Therapy of exacerbated COPD . How long ambulatory treatment?}; Behr J; Acute exacerbation of COPD impacts negatively on the prognosis, and is associated with a significant motality rate . Accordingly, every case of COPD exacerbation requires intensified treatment of the underlying disease . This usually ecompasses the use of inhalative and possibly also systemic bronchodilators, and systemic glucocorticosteroids at appropriate doses . Evidence of infection (purulent sputum) indicates the need for an antibiotic, the choice of which must be determined by the severity of the underlying disease . Respiratory insufficiency requires the additional use of oxygen and, where necessary, mechanical ventilation . In such cases, non-invasive ventilation via a mask has resulted in an appreciable reduction in the complications associated with invasive ventilation, and a significant reduction in the associated high mortality rates . Successful treatment of COPD exacerbation must be followed by suitable measures aimed at reducing future episodes of exacerbation . These includes smoking cessation, optimal medical treatment and vaccination against influenza, together with appropriate patient instruction. Curr Opin Infect Dis, 2003 Jun, 16(3), 259 - 63 Epidemiology and spectrum of disease of Escherichia coli O157; Ochoa TJ et al.; PURPOSE OF REVIEW: The Shiga toxin-producing Escherichia coli strains, such as E . coli O157:H7, have emerged as major diarrheal pathogens both in the United States and elsewhere . These organisms are important because gastrointestinal infection (afebrile hemorrhagic colitis) can trigger microangiopathic hemolytic anemia and renal failure (hemolytic uremic syndrome) . Understanding the pathophysiology of this illness is likely to lead to important new treatment interventions . RECENT FINDINGS: It is now recognized that children with hemorrhagic colitis routinely develop a spectrum of coagulation abnormalities and that only a fraction of children develop full blown hemolytic uremic syndrome . Individual variability in expression of inflammatory mediators is likely to be a key element in determining which children progress to the severe end of the spectrum of disease . The value of antibiotic therapy is unknown . SUMMARY: The pathophysiology of HUS remains incompletely understood . The lag between onset of diarrhea and onset of HUS represents an opportunity to intervene and prevent renal failure . However, there currently is no way to prevent such life threatening complications . The management should focus on diagnosis and close observation so that early intervention can prevent complications. Neurology, 2003 Jun 24, 60(12), 1923 - 30 Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial; Krupp LB et al.; OBJECTIVE: To determine whether post Lyme syndrome (PLS) is antibiotic responsive . METHODS: The authors conducted a single-center randomized double-masked placebo-controlled trial on 55 patients with Lyme disease with persistent severe fatigue at least 6 or more months after antibiotic therapy . Patients were randomly assigned to receive 28 days of IV ceftriaxone or placebo . The primary clinical outcomes were improvement in fatigue, defined by a change of 0.7 points or more on an 11-item fatigue questionnaire, and improvement in cognitive function (mental speed), defined by a change of 25% or more on a test of reaction time . The primary laboratory outcome was an experimental measure of CSF infection, outer surface protein A (OspA) . Outcome data were collected at the 6-month visit . RESULTS: Patients assigned to ceftriaxone showed improvement in disabling fatigue compared to the placebo group (rate ratio, 3.5; 95% CI, 1.50 to 8.03; p = 0.001) . No beneficial treatment effect was observed for cognitive function or the laboratory measure of persistent infection . Four patients, three of whom were on placebo, had adverse events associated with treatment, which required hospitalization . CONCLUSIONS: Ceftriaxone therapy in patients with PLS with severe fatigue was associated with an improvement in fatigue but not with cognitive function or an experimental laboratory measure of infection in this study . Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with PLS. Eur J Pediatr, 2003 Sep, 162(9), 576 - 81 Epub 2003 Jun 19. The burden of acute otitis media on the patient and the family; Greenberg D et al.; The aim of our study was to determine the burden of acute otitis media (AOM) on patients and their families . Parents of children with AOM were interviewed with regard to the week preceding the AOM diagnosis and every 3 days henceforth for an additional 21 days . The interview included information on loss of workdays, use of health care services and impact on the patient's and family's quality of life . Parents of age- and neighbourhood-matched controls were interviewed in an identical manner . A total of 150 patients and 51 controls were included in the analysis . The following variables differed significantly ( P<0.001) between patients and controls (mean +/- SD): non-routine days 18.5+/-11.0 in patients versus 3.4+/-6.5 in controls; number of visits to primary health centres 2.6+/-1.6 versus 0.4+/-0.6; number of emergency room visits 0.2+/-0.5 versus 0.1+/-0.02 and number of visits to an otolaryngology clinic 0.3+/-0.6 versus 0 . Days of antibiotic and over the counter drug use were 9.0+/-5.6 versus 0.3+/- 0.9 and 7.0+/-6.0 versus 4.9+/-6.0, respectively per episode . The mean loss of workdays per child was 1.6+/-1.8 in patients versus 0.25+/-0.6 in controls, for working mothers and 0.6+/-1.1 versus 0.1+/-0.4 for working fathers; duration of absenteeism from day care facilities was 3.5+/-2.5 versus 0.9+/-2.7 . CONCLUSION: Acute otitis media significantly reduces the quality of life of both child and parents, causes substantial use of medical services and significant loss of workdays. Br J Community Nurs, 2003 Jun, 8(6 Suppl), S36 - 42 Povidone-iodine as a topical antiseptic for treating and preventing wound infection: a literature review; Flynn J; With the proliferation of antibiotic and antiseptic resistant strains of bacteria around the world, attention is increasingly being focused on more 'traditional' methods of combating and preventing wound infections . This article examines the research literature pertaining to the use of povidone-iodine, a form of iodine commonly used for skin cleansing, as a prophylaxis or treatment for wound infection . The literature is discussed as it relates to the ideal characteristics of an antiseptic for use on wounds proposed by Konig et al (1997) and Liptak (1997) . On the basis of available research, it appears that povidone-iodine should be promoted by nurses and other healthcare professionals involved in wound care as a means of preventing and treating infection in a range of acute and chronic wounds. Eur J Obstet Gynecol Reprod Biol, 2003 Jul 1, 109(1), 16 - 20 Delayed delivery of second twin: a multicentre study of 35 cases; Fayad S et al.; OBJECTIVE: The aim of this study was to conduct a statistical analysis to determine the outcome of conservative treatment after delivery of a first fetus in multiple pregnancy and thus define new prognostic factors . STUDY DESIGN: Multicentre retrospective study involving 12 centers over a 10-year period . RESULTS: Twenty-eight twin pregnancies and seven triplet pregnancies which were managed conservatively . In twin pregnancies, 79% of the delayed-delivery fetuses survived; only 7% of the first delivered fetuses survived . The mean interval between deliveries was 47 days . No statistical difference was found concerning cerclage, antibiotic therapy, tocolysis and hospitalization . Earlier delivery of the first twin and premature rupture of membranes for the second twin were significantly related to a longer interval between deliveries . CONCLUSION: Delayed delivery in multifetal pregnancies can be successful if there are no contraindications and these pregnancies are managed in a tertiary perinatal center . Publications limited to successful cases have undoubtedly introduced some bias in assessment. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw, 1998, 4(1), 19 - 25 {The thyroid function in children with purulent meningitis}; Szychowska Z et al.; Purulent meningitis (BM) is a complex process and its outcome is largely influenced by host's response, both inflammatory or endocrine, to the infection . In this study thyroid function in children with BM was investigated by measuring serum or plasma levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4) and free thyroxine (FT4) 3 times in course of the disease: at admission, after 24-48 hrs . of treatment and at recovery (day 10-14 from the onset of the disease) . The levels of hormones were measured by radioimmunoassay (RIA) or by enzyme linked fluorescent assay (ELFA) . A decrease in serum or plasma concentrations of all measured hormones was found at the beginning of BM as compared to the controls . This indicates the low T4 variant of sick euthyroid syndrome in children with BM, which usually occurs in seriously ill patients . The levels of measured hormones rose at recovery in comparison to their initial values, but T3 concentrations and TSH (TSH - measured by RIA) were still lower in comparison to the controls . Serum T3 concentrations were significantly lower in children with sequelae of BM than in children who recovered without sequelae . This indicates a possible adverse effect of disturbed thyroid function resulting in low-T3 syndrome on the outcome from BM . An adjunctive anti-inflammatory treatment with dexamethasone started 10-15 minutes before the first antibiotic dose and, given every 12 hrs in a dose of 0.4 mg/kg for 2 days, it resulted in greater decrease in T3, FT3, T4 and FT4 plasma levels in comparison to non-steroid treated children. Pol J Vet Sci, 2003, 6(2), 109 - 15 A comparative study of the effects of meloxicam and flunixin meglumine (NSAIDs) as adjunctive therapy on interferon and tumor necrosis factor production in calves suffering from enzootic bronchopneumonia; Bednarek D et al.; The study was performed on 18 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided into three groups and respectively treated with oxytetracycline and meloxicam--Group I (9 animals); oxytetracycline and flunixin meglumine--Group II (3 animals); and oxytetracycline only--Group III (6 animals--control) . The following observations were recorded before treatment (1st day) and two days later (3rd day): body temperature, the serum level of interferon (IFN) and tumor necrosis factor (TNF) as well as cytokine production by bronchoalveolar lavage (BAL) cells . The treatment of calves with a combination of oxytetracycline and meloxicam (Group I) and especially with oxytetracycline and flunixin meglumine (Group II) caused a significantly faster, in comparison to the control group, normalization of body temperature . Both drugs, meloxicam and especially flunixin meglumine, inhibited excessive TNF production in the organism (measured as the serum level of cytokine) . Moreover, BAL cells isolated from calves treated with both NSAIDs were still able, ex vivo, to release TNF, in contrast to the control group (treated only with tetracycline) which lost the ability to produce TNF . The treatment of the calves with meloxicam and flunixin meglumine did not significantly influence the levels of IFN in sera but normalized ex vivo IFN production in BAL cells . These results suggest that the combination of meloxicam with an antibiotic or flunixin meglumine with an antibiotic which does not exert an immunosuppressive influence on the organism of calves suffering from enzootic bronchopneumonia is equally effective in the treatment of calves and superior to the antibiotic alone. Sportverletz Sportschaden, 2003 Jun, 17(2), 84 - 7 {Vesiculitis seminalis--a rare diagnosis in case of chronic groin pain}; Kelm J et al.; In this case report we present a male soccer player suffering from chronic groin pain . Exact diagnosis, i . e . seminal vesiculitis, could finally be evaluated by the means of MR Imaging, and so the patient did fully recover after selective antibiotic therapy . In this case musculoskeletal involvement because of visceral pelvic disorders may be caused by synaptic interaction between the somato-sensory and viscero-motoric system due to the close anatomical relationship between the seminal vesicle of the pelvis and the pubic bone with its insertion of the adductor muscles . In case of chronic groin pain in athletes physicians should also be aware of visceral pelvic disorders . For diagnostic evaluation MR Imaging may be of important help. J Neurosurg, 2003 Jun, 98(6), 1203 - 7 Preservation of bone flaps in patients with postcraniotomy infections; Bruce JN et al.; OBJECT: Management of postcraniotomy wound infections has traditionally consisted of operative debridement and removal of devitalized bone flaps followed by delayed cranioplasty . The authors report the highly favorable results of a prospective study in which postcraniotomy wound infections were managed with surgical debridement to preserve the bone flaps and avoid cranioplasty . METHODS: Since 1990, 13 patients with postcraniotomy wound infections have been prospectively treated with open surgical debridement and replacement of the bone flap . All patients received a full course of systemic antibiotic agents based on the determination of the bacterial culture and antibiotic sensitivity . Notable risk factors for infection included prior craniotomies, radiotherapy, and skull base procedures . The mean long-term follow-up period was 35 +/- 20 months . In all five patients who underwent craniotomies without complications, bone flap preservation was possible with full resolution of the infection and without the need for additional surgery . Among the eight patients with risk factors, bone preservation was possible in six patients, although two required minor wound revisions (without bone flap removal) . Both patients who underwent craniofacial procedures required an additional procedure in which the bone flap was removed for recurrent infection (one after 2 months and the other after 29 months) . CONCLUSIONS: In patients with uncomplicated postcraniotomy infections, simple operative debridement is sufficient and it is not necessary to discard the bone flaps and perform cranioplasties . Even patients with risk factors such as prior surgery or radiotherapy can usually be treated using this strategy . Patients who undergo craniofacial surgeries involving the nasal sinuses are at higher risk and may require bone flap removal. Biofizika, 2003 May-Jun, 48(3), 436 - 42 {Kinetics of the lactone-carboxylate transition of hybrid camptothecin-netropsin molecules}; Oleinikov VA et al.; The kinetics of the hydrolysis of the lactone ring of a hybrid molecule containing the molecules of the antitumor drug camptothecin and a derivative of the antibiotic netropsines, which is highly affine and specific to the DNA A-T sequences was investigated . It was shown that intramolecular interaction significantly slows down the rate of hydrolysis but does not change the equilibrium ratio of concentrations of the lactone and carboxylate forms of the camptothecin fragment of the hybrid molecule, which corresponds to the pH value . The use of intramolecular interaction for controlling the kinetics of the lactone/carboxylate transition makes it possible to create the drugs of the camptothecin family, which preserve the biologically active lactone form under the physiological conditions for a longer time and, therefore, are more effective as anticancer agents. Folia Med Cracov, 2001, 42(4), 237 - 48 {Problems with infections during the perioperative period}; Rybicki Z; The paper addresses issues related to the prophylactic and empirical use of antibiotics in surgery . Apart from the factors related to post-operation infections, it presents recommendations and proposals for the prophylactic use of antibiotics in particular types of operations . The recommendations are based on the American and European specialist literature, with the differences between these two approaches clearly outlined . Additional comments are provided for the important elements of prophylactics in particular types of operations . In the part concerning the use of antibiotics in treatment of intra-abdominal infections, the focus is on the general rules for antibiotherapy in pancreatitis . There is also a discussion of mycotic complications accompanying intra-abdominal infections . The paper ends with specific indications for the empirical use of antibiotics in intra-abdominal infections. Drug Metab Dispos, 2003 Jul, 31(7), 878 - 87 In vitro metabolism of clindamycin in human liver and intestinal microsomes; Wynalda MA et al.; Incubations with human liver and gut microsomes revealed that the antibiotic, clindamycin, is primarily oxidized to form clindamycin sulfoxide . In this report, evidence is presented that the S-oxidation of clindamycin is primarily mediated by CYP3A . This conclusion is based upon several lines of in vitro evidence, including the following . 1) Incubations with clindamycin in hepatic microsomes from a panel of human donors showed that clindamycin sulfoxide formation correlated with CYP3A-catalyzed testosterone 6beta-hydroxylase activity; 2) coincubation with ketaconazole, a CYP3A4-specific inhibitor, markedly inhibited clindamycin S-oxidase activity; and 3) when clindamycin was incubated across a battery of recombinant heterologously expressed human cytochrome P450 (P450) enzymes, CYP3A4 possessed the highest clindamycin S-oxidase activity . A potential role for flavin-containing monooxygenases (FMOs) in clindamycin S-oxidation in human liver was also evaluated . Formation of clindamycin sulfoxide in human liver microsomes was unaffected either by heat pretreatment or by chemical inhibition (e.g., methimazole) . Furthermore, incubations with recombinant FMO isoforms revealed no detectable activity toward the formation of clindamycin sulfoxide . Beyond identifying the drug-metabolizing enzyme responsible for clindamycin S-oxidation, the ability of clindamycin to inhibit six human P450 enzymes was also evaluated . Of the P450 enzymes examined, only the activity of CYP3A4 was inhibited (approximately 26%) by coincubation with clindamycin (100 microM) . Thus, it is concluded that CYP3A4 appears to account for the largest proportion of the observed P450 catalytic clindamycin S-oxidase activity in vitro, and this activity may be extrapolated to the in vivo condition. Br J Clin Pharmacol, 2003 Jun, 55(6), 552 - 9 Population pharmacokinetics of netilmicin in short-term prophylactic treatment; Jauregizar N et al.; AIMS: To characterize the population pharmacokinetics of netilmicin, an aminoglycoside antibiotic, in adult urology patients and to develop a covariate model for improved dose titration . METHODS: Data from 62 adult patients (55 male, seven female), undergoing urological surgery and treated with netilmicin for short-term prophylaxis, were evaluated retrospectively . The group had (median, range) ages 68, 31-92 years, weights 72, 43-106 kg and heights 167, 148-182 cm . No patient showed renal impairment before netilmicin treatment (serum creatinine </=1.9 mg dl-1) . Netilmicin (100 mg) was administered as a maximum of four successive intravenous infusions of 30 min, at 8-h intervals . A total of five blood samples were collected from each patient . Prior to analysis, the dataset was divided into 'index' (n = 44) and 'validation' (n = 18) groups at random . The time courses of netilmicin concentrations from all subjects were analysed using a mixed effects, population, nonlinear modelling package (WinNonMix) . For covariate model development, a stepwise procedure was used with backward elimination followed by forward inclusion based on age, sex, weight, height, creatinine clearance and type of surgery . The final covariate model parameters from the index group were used to simulate concentrations in the validation group and the bias and precision were compared with the observations . RESULTS: A bi-compartmental open model with a proportional residual error best described the data . The population parameters for central and peripheral volumes of distribution were (typical population value {interindividual CV%}) Vc = 14.5 l {56%} and Vp = 10.2 l {not estimated}, and the systemic and intercompartmental clearances were CL = 3.9 l h-1{42%} and CLQ = 10.1 l h-1{not estimated}, respectively . The final population covariate relationships were based on sex (SEX) and creatinine clearance (CrCL): (Vc, l) = 18.9 - 5.9 x SEX {29%} and (CL, l h-1) = 0.06 x CrCL {33%} . Compared with the observations in the validation group, this model showed a bias (95% confidence interval) of -0.028 (-0.28, 0.25) and precision of 1.22 (0.78, 1.34) . CONCLUSION: Bi-compartmental pharmacokinetic parameters of netilmicin have been estimated from clinical data in urological surgery patients using a population approach . A given single dose results in large variability in plasma concentrations and thus the population covariate final model can be used for direct estimation of initial dosing in patients. Respir Med, 2003 Jun, 97(6), 660 - 6 Connective tissue responses in acute community-acquired pneumonia; Nordenbaek C et al.; Circulating connective tissue components including the aminoterminal propeptides of type III collagen (PIIINP), type I collagen (PINP) and hyaluronan were determined in patients hospitalised for pneumonia of suspected bacterial origin . Ninety patients were included, 64 of these were followed prospectively for up to 21 days after initiation of therapy . Serum PIIINP was determined by RIA, s-PINP by ELISA, and s-hyaluronan by a radiometric assay . S-PIIINP rose significantly above the zero value within 24 h in both pneumococcal pneumonia (T0: 5.3 microg/l, 95% CI: 2.7-8.1 microg/l vs . T1: 6.7 microg/l, 95% CI: 3.8-9.1, P<0.01) and in pneumonia of unknown aetiology (T0: 4.0 microg/l, 95% CI: 3.6-4.8 vs . T1: 4.5 microg/l, 95% CI: 3.8-5.1, P<0.05) followed by a gradual decline . At T1, S-PIIINP was higher in pneumococcal pneumonia compared with pneumonia of unknown aetiology (P<0.05) . By contrast, s-PINP tended to decline within 24 h in both pneumococcal pneumonia (T1: 30 microg/l, 95% CI: 23-40, ns) and in pneumonia of unknown aetiology (T1: 32 microg/l, 95% CI: 22-42, ns) followed by a steady increase . The PINP antigen size distribution remained constant throughout the follow-up period . S-hyaluronan in pneumococcal pneumonia paralleled s-PIIINP reaching a peak value on day 1 (121 microg/l, 95% CI: 65-191, P=0.38) . There was a positive correlation between s-PIIINP and C-reactive protein (CRP) . The study demonstrates, that community-acquired pneumonia elicits a differentiated mesenchymal response, which is turned down in response to successful antibiotic therapy. Zhonghua Shao Shang Za Zhi, 2003 Apr, 19(2), 75 - 7 {Clinical evaluation of the postburn retention and the metabolism of Imipenem in the third space}; Rong XZ et al.; OBJECTIVE: To explore the half life and retention of Imipenem in the third space . METHODS: Eight severely burned patients and eight healthy volunteers were enrolled as the burn group (B) and normal control group (C), respectively . HPLC (high performance liquid chromatography) was employed to determine the contents of Imipenem in the plasma, subeschar tissue fluid (STF) and the changes in its pharmacokinetics . Furthermore, the Imipenem content in the third space was calculated according to the systemic edema degree . RESULTS: The half life of Imipenem in STF (2.53 h) was longer than that in plasma (1.73 h), P < 0.05) . The Imipenem content in STF increased gradually along with the lapse of time after repeated intravenous infusion of Imipenem, and at the same the total content of lmipenem was increased significantly in the third space . CONCLUSION: There was antibiotic retention in the third space after severe burn injury, and a prolonged action of the drug could be expected when the drug re-entered the blood stream. J Cell Physiol, 2003 Aug, 196(2), 394 - 402 Geldanamycin inhibits migration of glioma cells in vitro: a potential role for hypoxia-inducible factor (HIF-1alpha) in glioma cell invasion; Zagzag D et al.; Focal adhesion kinase (FAK) and hypoxia-inducible factor (HIF-1alpha) are both up-regulated in glioblastoma multiforme (GBMs), particularly in invasive zones . Because FAK may play an important role in the invasion of glioma cells into the surrounding brain, we sought an agent that causes down-regulation of FAK phosphorylation as a potential inhibitor of brain tumor invasion and growth . Geldanamycin (GA), a benzoquinone ansamycin antibiotic, binds to heat shock protein 90 (Hsp90) and interferes with its function . GA inhibits the proliferation of various non-glial cells and has anti-tumor activity . Moreover, GA blocks HIF-regulated transcription of VEGF and inhibits the VEGF-induced phosphorylation of FAK and migration of endothelial cells . Here, we tested the effect of GA on glioma cell migration in vitro and its potential to down-regulate HIF-1alpha induction . Our results demonstrate that GA (i) decreases U87MG, LN229, and U251MG glioma cell migration; (ii) reduces cell migration independent of p53 and PTEN status; (iii) prevents migration at non-toxic concentrations; (iv) reduces phosphorylation of FAK; and (v) inhibits cobalt chloride (CoCl(2))-mediated induction of HIF-1alpha in glioma cells . To the best of our knowledge, this is the first report showing that GA can inhibit phosphorylation of FAK concomitant with a decrease in cellular migration . One of the most clinically relevant aspects of this study is that GA interferes with the induction of HIF-1alpha that has been linked with glioma cell migration and angiogenesis . Given the fact that GA is a small lipophilic molecule capable of penetrating the blood brain barrier together with the data presented here provide a strong rationale for its use or its analogues in the treatment of highly invasive GBMs . Arch Microbiol, 2003 Aug, 180(2), 101 - 7 Epub 2003 Jun 14. Identification of a gene cluster encoding meilingmycin biosynthesis among multiple polyketide synthase contigs isolated from Streptomyces nanchangensis NS3226; Sun Y et al.; A cluster encoding genes for the biosynthesis of meilingmycin, a macrolide antibiotic structurally similar to avermectin and milbemycin alpha11, was identified among seven uncharacterized polyketide synthase gene clusters isolated from Streptomyces nanchangensis NS3226 by hybridization with PCR products using primers derived from the sequences of aveE, aveF and a thioesterase domain of the avermectin biosynthetic gene cluster . Introduction of a 24.1-kb deletion by targeted gene replacement resulted in a loss of meilingmycin production, confirming that the gene cluster encodes biosynthesis of this important anthelminthic antibiotic compound . A sequenced 8.6-kb fragment had aveC and aveE homologues ( meiC and meiE) linked together, as in the avermectin gene cluster, but the arrangement of aveF ( meiF) and the thioesterase homologues differed . The results should pave the way to producing novel insecticidal compounds by generating hybrids between the two pathways. Neuroradiology, 2003 Jul, 45(7), 456 - 62 Epub 2003 Jun 17. Clinical, laboratory, psychiatric and magnetic resonance findings in patients with Sydenham chorea; Faustino PC et al.; The objective of this study was to determine the clinical and laboratory characteristics, psychiatric manifestations and magnetic resonance imaging (MRI) findings in children and adolescents with Sydenham chorea (SyC) . The imaging examination was repeated 1 year after the acute phase of SyC . There were 19 patients with a mean age of 11.7 years and a predominance of females (79%);68% had generalized chorea and 53% moderate chorea . SyC presented as an isolated manifestation in 74% . No association between SyC and obsessive-compulsive disorder was found . Mental health problems were present in 45% of the patients . MRI analysis revealed persistent alterations in the caudate nucleus in three patients (16%), who presented recurrent episodes of chorea during the study . In one patient, MRI revealed the presence of nodular heteropathy close to the caudate nucleus region . We conclude that attention problems can be associated with acute clinical features of SyC and persistent alterations in the basal nuclei, evidenced by MRI, can be found in some patients who tend to suffer prolonged attacks and a greater number of recurrences. Di Yi Jun Yi Da Xue Xue Bao, 2003 Jun, 23(6), 633 - 5 {Anatomic observation of the prostate for clinical application of local drug injection through the rectum for chronic prostatitis}; Cheng JP et al.; OBJECTIVE: To provide anatomic evidences for local drug injection through the rectum for treating chronic prostatitis and observe the therapeutic effect of this treatment . METHODS: Anatomic observation of the median sagittal plane of 16 male pelvic specimens was conducted, with special attention to the structures between the prostate and the rectum . The distance from the posterior wall of the prostate to the anterior wall of the rectum, the scope that allowed the entry of the puncture needle, the appropriate puncture depth, and the distance from the anus to the safe were carefully measured . Analysis of the clinical record was performed in 51 chronic prostatitis cases treated with local injection of prednisolone, antibiotic and lidocaine through the rectum . RESULTS: Only some fat tissues and venous plexus were found between the prostate and the anterior wall of the rectum, and the distance from posterior wall of the prostate to the anterior wall of the rectum averaged 5.773+/-0.710 mm . The scope for possible puncture was 15.408 8+/-1.438 2 mm with a depth of 15.703 1+/-0.944 1 mm . The maximum and minimum distances from the anus to the puncture were 47.594+/-2.432 mm and 35.781+/-1.850 mm, respectively . Among the 51 cases investigated, the total cure rate was 84.31%, and improvement was achieved in 13.73% of the case, with only one case (2%) failed to respond to the treatment . CONCLUSION: Local drug injection through the rectum can be ideal for the treatment of prostatitis for its safety and effectiveness. BMC Infect Dis . 2003 Jun 17;3(1):11. Determinants for hospitalization in " low-risk" community acquired pneumonia; Aliyu ZY et al.; BACKGROUND: A variable decision in managing community acquired pneumonia (CAP) is the initial site of care; in-patient versus outpatient . These variations persist despite comprehensive practice guidelines . Patients with a Pneumonia Severity Index (PSI) score lower than seventy have low risk for complications and outpatient antibiotic management is recommended in this group . These patients are generally below the age of fifty years, non-nursing home residents, HIV negative and have no major cardiac, hepatic, renal or malignant diseases . METHODS: A retrospective analysis of 296 low-risk CAP patients evaluated within a year one period at St . Agnes Hospital, Baltimore, Maryland was undertaken . All patients were assigned a PSI score . 208 (70%) were evaluated and discharged from the emergency department (E.D.) to complete outpatient antibiotic therapy, while 88 (30%) were hospitalized . Patients were sub-stratified into classes I-V according to PSI . A comparison of demographic, clinical, social and financial parameters was made between the E.D . discharged and hospitalized groups . RESULTS: Statistically significant differences in favor of the hospitalized group were noted for female gender (CI: 1.46-5.89, p= 0.0018), African Americans (CI: 0.31-0.73, p= 0.004), insurance coverage (CI: 0.19-0.63, p= 0.0034), temperature (CI: 0.04-0.09, p= 0.0001) and pulse rate (CI: 0.03-0.14, p= 0.0001) . No statistically significant differences were observed between the two groups for altered mental status, hypotension, tachypnea, laboratory/radiological parameters and social indicators (p>0.05) . The average length of stay for in-patients was 3.5 days at about eight time's higher cost than outpatient management . There was no difference in mortality or treatment failures between the two groups . The documentation rate and justifications for hospitalizing low risk CAP patients by admitting physicians was less than optimal . CONCLUSIONS: High fever, tachycardia, female gender, African- American race and medical insurance coverage are determinants for hospitalization among low risk CAP patients in our study . The average length of stay for in-patients was 3.5 days (3 to 5 days) . The cost of in-patient care was about eight times higher than outpatient management . This study supports the recommendation of using the PSI for E.D evaluation of patients in appropriate social settings. Pediatr Clin North Am, 2003 Apr, 50(2), 413 - 26 Treatment of pediatric sinusitis; Goldsmith AJ et al.; The successful management of RS in children relies on careful diagnosis, recognition of causative factors, and judicious yet adequate antibiotic usage . Refractory cases will require surgical therapy, with adenoidectomy as the first-line intervention and ESS reserved for those cases refractory to adenoidectomy . This overall approach will improve quality of life and prevent complications in children with RS. Pediatr Clin North Am, 2003 Apr, 50(2), 399 - 411 Modern management of acute otitis media; Weber SM et al.; Although recent clinical trials suggest that conjugate vaccination will be less effective for the prevention of AOM than for IPD, these trials have demonstrated impressive reductions in the incidence of AOM due to invasive and antibiotic-resistant pneumococcal serotypes . These data suggest that if serotype replacement does occur in immunized children, the causative agents are likely to be less virulent than vaccine strains . Furthermore, a recent cost-effectiveness analysis projected that immunization of healthy infants with the heptavalent conjugate vaccine could prevent over one million episodes of AOM and 12,000 cases of invasive pneumococcal disease . Because significant reductions have been demonstrated in the incidence of frequently recurrent AOM, children with the worst disease stand to benefit most from vaccination . Based on data currently available, however, the conjugate vaccine is not going to eradicate AOM . Consequently, there will continue to be a need to scrutinize the threshold for prescribing antibiotics . In addition, there will be an ongoing need for surgery in some cases of recurrent AOM and persistent OME. J Biomed Mater Res B Appl Biomater, 2003 Jul 15, 66(1), 457 - 86 Fatigue testing and performance of acrylic bone-cement materials: state-of-the-art review; Lewis G; Over the past three decades or so, a very large volume of literature has been generated on the impact of an assortment of variables on the fatigue lifetimes of a large number of acrylic bone-cement formulations . In the present article, this literature is examined critically to reveal areas of agreement, areas of disagreement, as well as a welter of underexplored and unexplored topics . For example, there is unanimity of support for the notion that an increase in the molecular weight of the powder constituents or the fully cured cement leads to an increase in the cement's fatigue life, whereas there is disagreement as to whether vacuum mixing the cement constituents leads to an increase in the fatigue life of the fully cured cement (relative to the hand-mixed counterpart) . Among the underexplored topics is systematic study of the effect of test frequency on the fatigue results, whereas determination of the optimal concentration of the antibiotic in an antibiotic-loaded cement is an example of the unexplored topics . It is pointed out that resolving the controversies, addressing the underexplored topics, and filling the lacunae will allow comprehensive evaluations of acrylic bone-cement materials to be made . This enhanced body of knowledge will prove invaluable in the continued use of acrylic bone cement as the anchoring agent in cemented arthroplasties . J Med Microbiol, 2003 Jul, 52(Pt 7), 557 - 61 Rapid identification and susceptibility testing of Mycobacterium tuberculosis from MGIT cultures with luciferase reporter mycobacteriophages; Banaiee N et al.; In a prospective study conducted in a diagnostic laboratory in Mexico City, luciferase reporter mycobacteriophages (LRPs) were evaluated for their utility and performance in identification and antibiotic-susceptibility testing of Mycobacterium tuberculosis complex (MTC) isolates from MGIT-960 cultures . Eighty-four consecutive MGIT cultures recovered from 54 patients were included in this study . The LRPs confirmed mycobacterial growth in 79 (94 %) of 84 MGIT cultures . Failure to confirm growth was due to low inoculum (n = 1) or growth with non-tuberculous mycobacteria (n = 4) . The median time to confirmation of MGIT cultures was 1 day (range 1-55) . Confirmed cultures were identified with p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP), a selective inhibitor of MTC species, and results obtained with LRPs were compared with those obtained by BACTEC-460 . The sensitivity and specificity of the LRP NAP test were respectively 97 and 100 %, and the median turnaround time for identification was 3 days with both methods . The accuracy and speed of the LRPs for susceptibility testing with rifampicin, streptomycin, isoniazid and ethambutol were compared with BACTEC-460 and discrepant results were tested by the conventional agar proportion method . In total, 72 MTC cultures were tested . The overall agreement between the LRPs and BACTEC-460 was 98.6 % . Four isolates (5.6 %) were falsely identified as ethambutol-resistant . The median turnaround time for susceptibility testing was 3 days (range 3-57) with the LRPs and 9 days (range 7-29) with BACTEC-460 . LRPs offer an accurate and rapid approach for identification and susceptibility testing of M . tuberculosis from MGIT-960 cultures. J Toxicol Clin Toxicol, 2003, 41(3), 229 - 33 Unintentional human exposure to tilmicosin (Micotil 300); Von Essen S et al.; BACKGROUND: Tilmicosin phosphate is a macrolide antibiotic that is used to treat cattle for pathogens that cause Bovine Respiratory Disease . CASE REPORT: A 28-year-old man with no prior history of heart disease developed severe chest pain, inverted T waves, and intraventricular conduction delay on EKG and mild elevation of cardiac enzymes 5 hours after unintentional injection of less than half of a 12cc syringe filled with Micotil 300 (tilmicosin phosphate 300 mg/mL, propylene glycol 25%, phosphoric acid, water for injection) . The patient made an uneventful recovery after hospitalization . CONCLUSIONS: This case provides evidence that unintentional injection of tilmicosin can cause cardiac symptoms and laboratory evidence of myocardial injury . Tilmicosin should always be administered by properly trained personnel who are using techniques designed to reduce the risk of accidental self-injection. J Reconstr Microsurg, 2003 Apr, 19(3), 163 - 71 Treatment of post-traumatic tibial osteomyelitis using microsurgical flaps; Zumiotti AV et al.; Between 1994 and 1998, the authors treated 70 patients presenting with post-traumatic tibial osteomyelitis . Eighty-five percent were males, with a mean patient age of 32 years . The mean duration of the disease was 2 years . Fifty-one percent were of type IV in the Cierny-Mader classification . The mean follow-up period was 36 months . Case management was through thorough debridement, antibiotic therapy, and soft-tissue reconstruction using free flaps: latissimus dorsi (39.4 percent), scapular (28.2 percent), lateral arm (19.7 percent), and anterior serratus (12.7 percent) . To evaluate the results, the control of infection and the quality of the soft tissue repaired were considered . The success rate was 90 percent . The authors conclude that their described method constitutes an effective treatment for post-traumatic tibial osteomyelitis. Curr Opin Pulm Med, 2003 Jul, 9(4), 261 - 5 Hepatic hydrothorax; Kinasewitz GT et al.; A hepatic hydrothorax is a pleural effusion that develops in a patient with cirrhosis and portal hypertension in the absence of cardiopulmonary disease . The pleural effusion is derived from ascitic fluid that enters the chest because of the negative pressure within the pleural space via defects in the diaphragm . The peritoneal-to-pleural flow of fluid can be demonstrated by nuclear scanning, even when the ascites is not clinically apparent . The pleural fluid usually has the characteristics of a transudate . However, an occasional patient with hepatic hydrothorax will develop spontaneous bacterial pleuritis manifest by increased pleural fluid neutrophils or a positive bacterial culture and will require antibiotic therapy . Treatment of the hydrothorax is directed at the underlying liver disease but a dyspneic patient can obtain relief from a thoracentesis or paracentesis . When medical therapy fails, liver transplantation is the treatment of choice . Both transjugular intrahepatic portosystemic shunting and thoracoscopic repair of diaphragmatic defects with pleural sclerosis can provide symptomatic relief, but the morbidity and mortality of these procedures are high because of the fragile nature of the patients. Brain, 2003 Jul, 126(Pt 7), 1628 - 37 Epub 2003 Jun 04. Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice; Wells JE et al.; Acute spinal cord injury (SCI) produces tissue damage that continues to evolve days and weeks after the initial insult, with corresponding functional impairments . Reducing the extent of progressive tissue loss ('neuroprotection') following SCI should result in a better recovery from SCI, but treatment options have thus far been limited . In this study, we have tested the efficacy of minocycline in ameliorating damage following acute SCI in mice . This semi-synthetic tetracycline antibiotic has been reported to inhibit the expression and activity of several mediators of tissue injury, including inflammatory cytokines, free radicals and matrix metalloproteinases, making it a suitable candidate for study . Mice were subjected to extradural compression of the spinal cord using a modified aneurysm clip, following which they received treatment with either minocycline or vehicle beginning 1 h after injury . Behavioural testing of hindlimb function was initiated 3 days after injury using the Basso Beattie Bresnahan locomotor rating scale, and at 1 week using the inclined plane test . Functional assessments demonstrated that minocycline administration significantly improved both hindlimb function and strength from 3 to 28 days after injury compared with vehicle controls . Furthermore, gross lesion size in the spinal cord was significantly reduced by minocycline, and there was evidence of axonal sparing as determined using fluorogold labelling of the rubrospinal tract and by Bielchowsky silver stain . Finally, a comparison of minocycline against the currently approved treatment for acute SCI in humans, methylprednisolone, demonstrated superior behavioural recovery in the minocycline-treated animals. J Womens Health (Larchmt), 2003 Apr, 12(3), 255 - 9 A pilot study of treatment of bacterial vaginosis with a buffering vaginal microbicide; Harwell JI et al.; BACKGROUND: Bacterial vaginosis (BV) is an extremely common problem for women and is associated with adverse pregnancy outcomes and HIV infection . Currently available antibiotic treatments are moderately effective but may need to be repeated frequently because of the recurrent nature of the disease . We undertook a pilot study of a buffering vaginal microbicide in the treatment of BV . METHODS: Women with clinically diagnosed BV were recruited to receive seven applications (5 g per application) of BufferGel trade mark (ReProtect, LLC, Baltimore, MD), a topical vaginal microbicide, and had clinical and gram stain evaluation of response . Subjects were evaluated at 2-3 days after the last application of BufferGel as a test of cure and again at 1 month to assess for relapse . Subjects with BV at test of cure were offered oral metronidazole . RESULTS: Thirty-one women were screened, 16 were offered enrollment, and 10 completed the study . Treatment with BufferGel was clinically effective in 70% of women at 2-3 days after treatment and in 40% of women by 1-month follow-up . CONCLUSIONS: These results suggest that 5 g of BufferGel vaginally once a day appears to be a moderately effective treatment for BV. J Pharm Pharmacol, 2003 Apr, 55(4), 469 - 77 Effect of severe protein-calorie malnutrition on the penetration kinetics of trimethoprim and sulfamethoxazole to the deep tissues of Wistar rats; Lares-Asseff I et al.; This study shows the effect that severe malnourishment has on the kinetics of antibiotic penetration in tissues . A total of 104 male Wistar rats, 21 days old, were randomly divided into eight groups . Five groups of experimental rats were severely malnourished (SM) and three further groups were considered well-nourished control groups (WN) . A single dose of trimethoprim-sulfamethoxazole (TMP-SMX) was administered intraperitoneally . Blood samples were taken by heart puncture and five organs were extracted 0-24 h after the administration of the drug . HPLC was used to assess the amount of trimethoprim and sulfamethoxazole in fluids . The elimination half-life for trimethoprim from plasma was longer in SM rats with a median of 3.15 h; in WN rats, it was 0.390 h . Clearance was slower in SM rats: 646.72 mL microg(-1) h(-1) vs 3036.38 mL microg(-1) h(-1) in WN rats (P < 0.05) . Tissue penetration was much higher for trimethoprim, with penetration indexes of 0.80-5.66 in WN rats, compared with 0.35-2.14 in SM rats . In the case of sulfamethoxazole, penetration indexes were 0.029-1.13 for WN and 0.075-0.657 for SM rats . Similarly, the penetration ratio to muscle and heart tissue was lower in SM rats . However, penetration to kidney, lung, liver and spleen was greater in SM rats . It is evident that severe SM decreases the capacity of trimethoprim more importantly than sulfamethoxazole biotransformation. Can J Urol, 1995 May, 2(2), 144 - 7 Fournier's gangrene: nine cases of necrotizing infection of the male genitalia; Crofts NG et al.; Between 1989 and 1993, nine patients with Fournier's gangrene presented to our institution . The mean patient age was 66 years . The source of infection was dermal in five cases, urethral in three cases and rectal in one case . Potential contributing factors included diabetes mellitus in six cases, alcohol abuse in four cases and drug-induces immunosuppression in two cases . In every patient, tissue cultures revealed mixed aerobic and anaerobic infections . All patients were treated initially with aggressive surgical debridement and culture-specific intravenous antibiotics . One patient required multiple debridements . Reconstruction by split-thickness skin grafts was performed in eight cases and one healed by secondary intention . There were no deaths due to progressive infection . The mortality rate was 11% with six month follow-up . The favorable outcome of patients in this series supports the current recommendation for early, aggressive surgical debridement and culture-specific, intravenous antibiotic therapy. Antibiot Khimioter, 2003, 48(2), 9 - 12 {Effect of fosfidomycin on development of various infections in mice}; Potapov VD et al.; Antibiotic fosmidomycin will know as inhibitor of the nonmevalonate pathway of isoprenoid biosynthesis and as possible antimalarial drug, was shown to possess a certain protective effect on mice experimentally infected with tularemia, tiphus or coli-septicemia . Positive effect on mice with chronic form of tuberculosis was not observed when the animals were given 1 mg of fosmidomycin per capita twice a day . Under oxidative conditions an ESR signal of long living nitroxil free radicals were registered in the water solution of fosmidomycin . The radicals are supposed to be involved in the therapeutic effect of the antibiotic. Carbohydr Res, 2003 Jun 23, 338(13), 1359 - 67 Synthesis and antitumor activity of new D-galactose-containing derivatives of doxorubicin; Olsufyeva EN et al.; A general scheme of synthesis of antibiotic doxorubicin derivatives is based on the 13-dimethyl ketal of 14-bromodaunorubicin (4) . The interaction of 4 with melibiose (5), lactose (6), 3-methoxy-4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-4-oxybenzaldehyde (12) or 4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-4-oxybenzaldehyde (13) by reductive alkylation followed by hydrolysis of the corresponding intermediate bromoketals produced 3'-N-{alpha-D-galactopyranosyl-(1-->6)-O-1-deoxy-D-glucit-1-yl}doxorubicin (7), 3'-N-{beta-D-galactopyranosyl-(1-->4)-O-1-deoxy-D-glucit-1-yl}doxorubicin (8), 3'-N-{3"-methoxy-4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl}doxorubicin (16), and 3'-N-{4"-O-(beta-D-galactopyranosyl)-4"-oxybenzyl}doxorubicin (17) . Cytotoxic and antitumor activity of the synthesized drug candidates compared to the parent doxorubicin was studied using various experimental models, in particular, on mice bearing lymphocyte leukemia P-388 at single and multiple i.v . injection regimens. Fertil Steril, 2003 Jun, 79 Suppl 3, 1665 - 7 Seminal infection with Ralstonia picketti and cytolysosomal spermophagy in a previously fertile man; Carrell DT et al.; OBJECTIVE: To determine the origin of large plaque-like cellular and acellular masses of debris found in the semen of a patient with otherwise normal semen quality and secondary infertility . DESIGN: A prospective case study . SETTINGS: Academic andrology laboratory . PATIENT(S): Secondary infertility patient presenting for routine semen evaluation . INTERVENTION(S): Following diagnosis of a seminal infection, the patient was treated with an antibiotic . MAIN OUTCOME MEASURE(S): Semen quality parameters, semen culture, and electron microscopy identification of cytolysosomal spermophagy . RESULT(S): Semen culture identified a rare infection with Ralstonia picketti and electron microscopy showed massive neutrophil and cytolysosomal spermophagy . Both were eliminated after antibiotic therapy . CONCLUSION(S): This case study documents a rare infection of the reproductive tract with Ralstonia picketti . Analysis of large seminal masses determined their origin to be primarily from acellular cytolysosomes . The presence of such masses in semen should be further evaluated, including semen culture. Dig Liver Dis, 2003 Apr, 35(4), 217 - 21 A negative rapid urease test is unreliable for exclusion of Helicobacter pylori infection during acute phase of ulcer bleeding . A prospective case control study; Schilling D et al.; BACKGROUND: The reliability of the rapid urease test has not been proven in patients with peptic ulcer bleeding . Some studies show bad diagnostic results with the rapid urease test for gastrointestinal bleeding . AIMS: To evaluate the efficacy of the rapid urease test in patients with bleeding gastric or duodenal ulcers . PATIENTS AND METHODS: A total of 96 patients with acute peptic ulcer bleeding without proton pump inhibitor or antibiotic therapy within the last 14 days before bleeding were included into the study . During index endoscopy, specimens for histological and rapid urease test were obtained from the antrum and corpus mucosa of the stomach . Patients were also investigated by the 13C-urea breath test . Diagnostic quality parameters were calculated with the histology and the 13C-urea breath test as reference and compared with a matched control group with uncomplicated ulcers . RESULTS: The sensitivity of the rapid urease test was 80% and the specificity 100% compared to histology and 13C-urea breath test . The negative predictive value was 75% . These values were statistically significantly different from those of the control group (sensitivity 96%, specificity 100%, negative predictive value 88%) . CONCLUSION: The exclusive use of the rapid urease test cannot be recommended in patients with peptic ulcer bleeding. Clin Cornerstone, 2003, 5(2), 56 - 63 Insulin therapy for the critically ill patient; Van den Berghe G; The risk of mortality or significant morbidity is high among critically ill patients who are treated in the intensive care unit (ICU) for > 5 days . These patients are susceptible to sepsis, excessive inflammation, critical illness polyneuropathy, and multiple organ failure, the latter often being the cause of death . Most intensive care patients, even those who did not previously suffer from diabetes, are hyperglycemic, which is presumed to reflect an adaptive development of insulin resistance . In the K.U . Leuven study it was hypothesized that hyperglycemia is not a beneficial adaptation to severe illness but rather predisposes patients to many of the typical intensive care complications--prolonged intensive care dependence and death . The effects of intensive insulin therapy to maintain normoglycemia during critical illness were studied in a large group (N = 1548) of ventilated, surgical ICU patients . An algorithm was proposed for implementing this procedure . The randomly assigned intensive insulin therapy group received insulin infusion tailored to control blood glucose (BG) levels in the range 80-110 mg/dL, whereas the conventional treatment group received insulin only when glucose levels exceeded 200 mg/dL, and in that event were maintained in a target range of 180-200 mg/dL . Intensive insulin therapy induced a 43% reduction of intensive care mortality risk (P = 0.036 after correction for interim analyses) and a 34% reduction of hospital mortality (P = 0.005) . A reduced risk of severe infections by 46% (P = 0.003) was associated with a 35% reduction in prolonged (> 10 d) requirement for antibiotic therapy (P < 0.001) . In addition, excessive inflammation was prevented . Logistic regression analysis indicated that control of BG levels, rather than insulin administration itself, likely explains the observed clinical benefits . Use of insulin infusion to maintain normoglycemia using a titration algorithm, at least in populations similar to those in the Leuven study, improves outcome . Further data are needed to establish the applicability of this strategy to other patient groups, such as those in a medical ICU and in general hospital care. Pediatr Infect Dis J, 2003 Jun, 22(6), 540 - 5 Impact of palivizumab prophylaxis on respiratory syncytial virus hospitalizations in high risk Alaska Native infants; Singleton R et al.; BACKGROUND: Alaska Native children experience extremely high rates of hospitalization for respiratory syncytial virus (RSV) infection . We evaluated the effect of palivizumab prophylaxis on the incidence of RSV hospitalizations in high risk Alaska Native children . METHODS: We analyzed two retrospective cohorts . The first analysis, of southwest Alaska Native children hospitalized with acute respiratory infections during 1993 to 1996 and 1998 to 2001, compared RSV hospitalization rates among premature and nonpremature infants born before (1993 to 1996) and after (1998 to 2001) palivizumab use . The second analysis, of Alaska Native infants with a history of prematurity or lung disease during 1998 through 2001, compared RSV hospitalization among children receiving palivizumab during protected periods (within 32 days after a dose of palivizumab) and unprotected periods . RESULTS: First RSV hospitalizations in premature infants from southwest Alaska meeting criteria for palivizumab prophylaxis decreased from 439 per 1000 births before to 150 per 1000 births after palivizumab (relative rate, 0.34; 95% confidence interval, 0.17 to 0.68), whereas the rate in nonpremature infants remained stable (148 per 1000 births compared with 142 per 1000) . Among high risk Alaska Native children during 1998 through 2001, the rate of first RSV hospitalization was 0.55 per 1000 protected days and 1.07 per 1000 unprotected days (relative rate, 0.52; 95% confidence interval, 0.28 to 0.93) . CONCLUSIONS: Palivizumab reduced RSV hospitalizations in high risk infants in a region with high rates of RSV hospitalization. Ophthalmology, 2003 Jun, 110(6), 1126 - 36 Tectonic corneal lamellar grafting for severe scleral melting after pterygium surgery; Ti SE et al.; PURPOSE: To describe the technique and review the indications and success of tectonic corneal lamellar grafting for the management of severe scleral melts after pterygium surgery . DESIGN: Retrospective, noncomparative, interventional case series . PARTICIPANTS: Twenty cases of severe scleral necrosis after pterygium surgery (1993-1999) . INTERVENTION: Tectonic corneal lamellar grafting . Surgery involved (1) removal of all devitalized or infected scleral tissue surrounding the melt; (2) use of lamellar or full-thickness donor corneal tissue, fashioned to fit the scleral defect exactly or a 0.25-mm diameter larger; and (3) placement of a pedicled or free conjunctival flap over the corneal lamellar graft . MAIN OUTCOME MEASURES: Eradication of progressive scleral necrosis, preservation of globe integrity, eradication of infection, and preoperative and postoperative visual acuity . RESULTS: Sixteen (80%) of 20 cases developed severe scleral necrosis that required tectonic surgery after bare sclera pterygium excision with mitomycin C or beta-irradiation . Surgery was also therapeutic to eradicate progressive infection in 6 cases of infective scleritis that did not respond to maximal medical treatment . Scleral melting presented 1 month to 20 years after initial pterygium surgery in healthy, immune-competent adults . Therapeutic and tectonic success was achieved in 19 cases (95%); in 1 case, recurrence of fusarium fungal infection led to severe graft necrosis and intraocular spread . Among the cases of infectious scleritis, three eyes required repeat lamellar grafting to successfully eradicate infection . CONCLUSIONS: Tectonic and therapeutic lamellar keratoplasty, combined with aggressive antibiotic therapy, preserved globe integrity and eradicated infection in ca