Am Surg, 2002 Aug, 68(8), 709 - 13 Management of Fournier's gangrene: an eleven year retrospective analysis of early recognition, diagnosis, and treatment; Norton KS et al.; Fournier's gangrene is an infectious necrotizing fasciitis of the perineum and genital regions . It is a synergistic infection caused by a mixture of aerobic and anaerobic organisms . The mortality rate from this infection ranges from 0 to 67 per cent . One of the most important determinants of overall outcome is early recognition and extensive surgical debridement upon initial diagnosis . This is followed by aggressive antibiotic therapy combined with other precautionary and resuscitative measures . Our hypothesis is that early aggressive surgical debridement combined with broad-spectrum antibiotic coverage results in decreased mortality from Fournier gangrene . The objective of this study was to determine our morbidity and mortality as compared with other institutions . This was a retrospective review of 200 charts of patients from 1990 through 2001 . The charts reviewed included patients with a diagnosis of male and female genital abscesses, cellulitis, necrotizing fasciitis, and vascular disorders . This resulted in 33 patients who had a final diagnosis of Fournier's gangrene . There were 26 (79%) males and seven (21%) females with a diagnosis of Fournier's gangrene . The patients ranged in age from 30 to 85 years (mean age 51.5) . There were a number of predisposing factors that were examined . Thirteen patients (39%) were diabetic, 18 (55%) suffered from hypertension, 18 (55%) were obese, and 18 (55%) were cigarette smokers . Four patients (12%) had no predisposing factors . The treatment consisted of wide surgical debridement which was performed in all 33 patients . Most patients received multiple debridements ranging from one surgery to seven (mean 3.25) per hospital stay . The majority of patients received broad-spectrum antibiotic coverage . Three patients died, which resulted in a mortality rate of 9 per cent . Early recognition and aggressive surgical debridement is the most essential intervention in stopping the rapidly progressing infectious process of Fournier's gangrene . This intervention should be combined with aggressive triple-antibiotic therapy and other precautionary measures for supporting the patient who has the systemic effects of Fournier's gangrene . Our data do not reach statistical significance with regard to the use of triple-antibiotic therapy . However, we believe that it is an important part of the treatment regimen . The combination of aggressive surgical therapy and appropriate antibiotic coverage results in a reduction in mortality. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 1997, 29(3), 251 - 258 The Discovery of Streptomycin-binding IgG and Its Distribution in the Population; Hu CQ et al.; It was found by using several immunochemistry methods that a kind of immunoglobulin G (IgG) which accounted for 0.5%-1% of the total IgG in human, rabbit or mice with no history of taking any streptomycin could bind specifically with the antibiotic . Although the IgG-binding action has not relation with the specificity of the antibody, the streptomycin-binding area was found to be on the antigen-binding region of Fab fragment of the antibody . This kind of IgG was termed streptomycin-binding IgG (SMBIgG) which may be capable of catalyzing the metabolism of streptomycin . The average content of SMBIgG in human and rabbit sera is about 0.1 mg/ml, with no samples with a lower level than the mean value, but in a few cases levels two or three times higher than the mean were detected . Further study indicated that the ratio of SMBIgG to total IgG is nearly constant in the population . The discovery of SMBIgG in the normal body and its catalytic characteristic may be very helpful for understanding some of the special physiological functions of the antibody in the organism. Sex Transm Dis, 2002 Sep, 29(9), 514 - 9 Examination of Chlamydia trachomatis infection in environments mimicking normal and abnormal vaginal pH; Yasin B et al.; BACKGROUND: It has long been assumed that a healthy acidic vaginal environment inhibits infection by Chlamydia trachomatis . The research objectives were to evaluate the effect of pH on C trachomatis infection by two in vitro methods, to assess pH effect at different serial dilutions of C trachomatis elementary bodies (EBs), and to examine protection by an antibiotic peptide, protegrin (PG-1), over a pH range . GOALS: The goals of this study were to test the hypothesis that acidic pH inhibits C trachomatis infection and to determine the ability of PG-1 to provide protection at acidic and neutral pH . STUDY DESIGN: The effect of pH on C trachomatis was examined using two pH-adjusted preincubation shell vial assays . C trachomatis EBs (serovars L2, D, and E) were exposed to pH-adjusted media, with and without PG-1, and infection was assessed by inclusion forming unit (IFU) formation in McCoy cell monolayers . RESULTS: Acidic pH in preincubation media markedly decreased IFUs by both in vitro methods . Serial dilution experiments showed a 3- to 10-fold reduction in IFUs for C trachomatis (L2 and E) at pH 5.0, compared with those at pH 7.5 . C trachomatis (D) showed a 17- to 23-fold reduction in IFUs (serial dilutions 1:1-1:4) . PG-1 protected McCoy cell monolayers from infection by C trachomatis after exposure to varied pH environments . CONCLUSION: Acidic pH exposure significantly reduced C trachomatis infection in vitro . Our results support the hypothesis that a healthy acidic vaginal environment protects women from C trachomatis infection . In addition, antibiotic peptides may provide protection as topical microbicides, regardless of vaginal pH. Chemotherapy, 2002 Sep, 48(4), 161 - 3 Effect of physical activity on the pharmacokinetics of ceftazidime in mice; Rule R et al.; BACKGROUND: The aim of the present work was to assess comparatively the pharmacokinetic profile of ceftazidime (CAZ) in trained and non-trained mice . METHODS: The study was performed on 256 mice divided at random into four groups: long-term physically trained mice with (E1a) and without (E1b) physical activity prior to the administration of CAZ, and untrained mice with (E2a) and without (E2b) physical activity prior to the administration of the antibiotic . CAZ was administered intramuscularly (25 mg/kg) to all mice, and blood samples were obtained at different time points . The plasma concentrations of CAZ were determined by HPLC and analyzed by non-compartmental models . RESULTS: The area under the curves in groups E1a and E2a (27.3 and 22.9 microg x ml(-1) x h, respectively) were different compared to the other groups {(E1b) = 11.1 and (E2b) = 15.6 microg x ml(-1) x h; p < 0.05} . Differences were observed between the concentration-time of CAZ in E1a compared to E1b, E1a versus E2a, E1a versus E2b, E1b versus E2a and E1b versus E2b (p < 0.05) . CONCLUSION: Physical activity performed prior to CAZ administration modified the pharmacokinetic profile of the drug administered to mice . J Bacteriol, 2002 Oct, 184(19), 5402 - 9 Formation of protoanemonin from 2-chloro-cis,cis-muconate by the combined action of muconate cycloisomerase and muconolactone isomerase; Skiba A et al.; Muconate cycloisomerases are known to catalyze the reversible conversion of 2-chloro-cis,cis-muconate by 1,4- and 3,6-cycloisomerization into (4S)-(+)-2-chloro- and (4R/5S)-(+)-5-chloromuconolactone . 2-Chloromuconolactone is transformed by muconolactone isomerase with concomitant dechlorination and decarboxylation into the antibiotic protoanemonin . The low k(cat) for this compound compared to that for 5-chloromuconolactone suggests that protoanemonin formation is of minor importance . However, since 2-chloromuconolactone is the initially predominant product of 2-chloromuconate cycloisomerization, significant amounts of protoanemonin were formed in reaction mixtures containing large amounts of muconolactone isomerase and small amounts of muconate cycloisomerase . Such enzyme ratios resemble those observed in cell extracts of benzoate-grown cells of Ralstonia eutropha JMP134 . In contrast, cis-dienelactone was the predominant product formed by enzyme preparations, in which muconolactone isomerase was in vitro rate limiting . In reaction mixtures containing chloromuconate cycloisomerase and muconolactone isomerase, only minute amounts of protoanemonin were detected, indicating that only small amounts of 2-chloromuconolactone were formed by cycloisomerization and that chloromuconate cycloisomerase actually preferentially catalyzes a 3,6-cycloisomerization. J Mol Biol, 2002 Sep 13, 322(2), 273 - 9 The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo; Thompson J et al.; The oxazolidinone family is a new class of synthetic antibiotics that bind to the bacterial 50S ribosomal subunit . Two members of the family, linezolid and XA043, were examined for their effects on translational fidelity using a lacZ reporter gene in vivo . Both promoted highly significant frameshifting and nonsense suppression . Chloramphenicol, a peptidyl transferase inhibitor, affected translational fidelity in a similar fashion . Neither the oxazolidinones nor chloramphenicol stimulated misincorporation of amino acid residues at position 461 in the lacZ gene . In contrast, the aminoglycosides gentamicin and paromomycin, which interact with the decoding region of the 30S subunit, caused significant misincorporation but only modest increases in frameshifting or stop codon readthrough of the lacZ gene . We conclude that effects on translational fidelity may play a significant role in the mechanism of action of the oxazolidinones. Salud Publica Mex, 2002 Jul-Aug, 44(4), 303 - 14 {Beliefs and knowledge of a group of doctors about the nutritional management of the child with acute diarrhea}; Corral-Terrazas M et al.; OBJECTIVE: To identify the beliefs and knowledge of a group of rural physicians on the dietary management of children under five years of age, with acute diarrhea . Physicians' dietary management was compared with that recommended by the World Health Organization . MATERIAL AND METHODS: A cognitive anthropology study was carried out from July to December 1998, on ten physicians that care for the infant population ascribed to Hospital Rural IMSS-Solidaridad of San Juanito Bocoyna, Chihuahua, Mexico . Data were collected through focus groups, case vignettes, free listing, pile sorting, and a semi-structured questionnaire, and then cross-referred . RESULTS: The physicians recognized the negative impact of diarrhea on the nutritional state of the child, but not all of them evaluated this state . Prevailing interventions were antibiotic therapy, fluid management, and feeding recommendations . Among the latter, the most consistent were breastfeeding, delayed feeding, and gradual feeding . CONCLUSIONS: The obtained information is in conflict with WHO's recommendations, specially with that of sustained feeding . The English version of this paper is available at: http://www.insp.mx/salud/index.html. Rev Esp Anestesiol Reanim, 2002 May, 49(5), 261 - 7 {Epidural abscess and regional anesthesia}; Guasch Arevalo E et al.; An epidural abscess is a rare lesion whose consequences can cause high morbi-mortality, particularly in obstetrics, where it occurs in young, healthy patients . With increased use of regional anesthesia, the incidence of epidural abscess will increase . We therefore review the risk factors, most common etiology and clinical signs, which may be non-specific but are nevertheless suggestive . We also review available diagnostic methods . It may be difficult to distinguish epidural abscess from other causes of medullar compression, but prompt diagnosis is essential so that emergency surgical repair can proceed and neurological recovery will be as early and complete as possible . Appropriate antibiotic therapy should be aggressive . Basic aseptic measures are critical for preventing infection through epidural needles, as the presence of infection at the moment of puncture facilitates greater susceptibility to epidural abscess. Rev Gastroenterol Peru, 1998 May, 18(2), 135 - 144 {ASCITES IN HEPATIC CIRRHOSIS: RECOGNITION INVESTIGATIONAND TREATMENT}; Shah H et al.; Hepatic cirrhosis is the most common cause of ascites . It is caused by liver failure leading to complex interrelated circulatory and renal changes resulting in retention of sodium and water and portal hypertension localising that sodium and water in the peritoneum . Ascites is an important development in cirrhosis as it implies a generally poor long term prognosis . Investigation is important as ascites is not always dueto cirrhosis, may bethe consequence of complications of cirrhosis such as hepatocellular carcinoma, and may be associated with infection which is fatal if untreated . Most patients respond to treatment with sodium restriction and diuretic drugs . This treatment takes time, and increasingly doctors use therapeutic paracentesis with sodium restriction and diuretics to prevent recurrence of ascites . Paracentesis, however, is not without complications, and it is particularly important to give colloid replacement to prevent hypovolaemia which can lead to renal failure . Patients who do not respond to this treatment may be helped by a TIPSS procedure or a peritoneovenous shunt . However, these patients usually have very poor liverfunction and the possibility of fiver transplantation should be considered . Infection is a very serious complication of ascites (spontaneous bacterial peritonitis) and carries a generally poor prognosis.Antibiotic prophylaxis is important to prevent recurrence and liver transpiantation shoulcl be considered. J Biol Chem, 2002 Nov 8, 277(45), 42654 - 62 Epub 2002 Sep 03. N-terminal sequence and distal histidine residues are responsible for pH-regulated cytoplasmic membrane binding of human AMP deaminase isoform E; Mahnke-Zizelman DK et al.; Mammalian AMP deaminase 3 (AMPD3) enzymes reportedly bind to intracellular membranes, plasma lipid vesicles, and artificial lipid bilayers with associated alterations in enzyme conformation and function . However, proteolytic sensitivity of AMPD polypeptides makes it likely that prior studies were performed with N-truncated enzymes . This study uses erythrocyte ghosts to characterize the reversible cytoplasmic membrane association of human full-sized recombinant isoform E (AMPD3) . Membrane-bound isoform E exhibits diminished catalytic activity whereas low micromolar concentrations of the cationic antibiotic, neomycin, disrupt this protein-lipid interaction and relieve catalytic inhibition . The cytoplasmic membrane association of isoform E also displays an inverse correlation with pH in the physiological range . Diethyl pyrocarbonate (DEPC) modification of isoform E nearly abolishes its cytoplasmic membrane binding capacity, and this effect can be reversed by hydroxylamine . Difference spectra reveal that 18 of 29 histidine residues in each isoform E subunit are N-carbethoxylated by DEPC . These combined data demonstrate that protonated imidazole rings of histidine residues mediate a pH-responsive association of isoform E with anionic charges on the surface of the cytoplasmic membrane, possibly phosphatidylinositol 4,5-bisphosphate, a pure noncompetitive inhibitor of the enzyme . Finally, AMPD1 and a series of N-truncated AMPD3 enzymes are used to show that these behaviors are specific to isoform E and require up to 48 N-terminal amino acids, even though this stretch of sequence contains no histidine residues . The pH-responsive cytosol-membrane partitioning of isoform E may be an important mechanism for branch point regulation of adenylate catabolism. Acta Clin Belg, 2002 Jun-Jul, 57(3), 158 - 61 Is the black thyroid really an innocuous pathological finding? Nollevaux MC, Burlet M, Squifflet JP, Daumerie C, Rahier J, Lambert M. We report the case of a 24-year-old euthyroid woman in whom the discovery of a cold nodule in the left thyroid lobe led to a thyroidectomy . The surgical specimen was characterized by a diffuse black discoloration . Optical examination revealed brown granules within the apical portion of the follicular cells whereas ultrastructural studies showed intralysosomal lipofuscin-like deposits, all findings consistent with pathological descriptions reported in black thyroids associated with the intake of minocycline . Retrospectively, we were told that the patient had received this antibiotic for at least three years for the treatment of acne vulgaris . As experimental models have demonstrated potential antithyroid effects of the drug, it appears relevant to monitor thyroid tests in patients receiving long-term minocycline therapy. Biopolymers, 2002 Oct 15, 65(2), 95 - 110 Multinuclear NMR and FTIR studies of new polyoxaalkyl esters of lasalocid and their complexes with lithium and sodium cations; Pankiewicz R et al.; Three new polyoxaalkyl esters of lasalocid are synthesized . Their ability to form complexes with Li(+) and Na(+) cations is studied using multinuclear NMR methods, FTIR spectroscopy in the middle and far IR regions, and mass spectrometry . It is found that lasalocid esters form only 1:1 complexes with the metal cations . The results of the NMR study in pyridine show that the polyoxaalkyl chain of the ester does not influence the complex formation of the lasalocid part of the esters . The reason for this is the competition of the pyridine molecules in the complexation process of metal cations . In chloroform the properties of the complex formation have changed and the oxaalkyl chain plays an important role within the complexation process, as demonstrated by the dependence of the respective continuous absorptions in the far IR region on the length of the oxaalkyl chain (i.e., on the number of the oxygen atoms in the chain) . The modifications of the lasalocid molecule influences the complexation of the metal cation and probably the interactions with the membrane . An increase in antibiotic activity is found as a consequence of these changed interactions . Rev Gastroenterol Peru, 1998 Sep, 18(3), 264 - 272 {INGESTION OF CORROSIVE SUBSTANCES}; Contardo C; Every patient that ingests any caustic substance still constitutes a medical and surgical . The severity and extension of the chemical damage will basically depend on the concentration and quantity of the caustic substance ingested . Likewise, when a highly concentrated alkali or acid substance is ingested, the esophagus and stomach will be damaged, and this lesion could also spread to the duodenum, and in some cases to the jejunum . Furthermore, it may compromise adjacent organs with a high morbimortality . The severity degree of the lesion can be determined with no risk by a flexible endoscopy, and correlates well with the intensity of tissue damage, enabling us to decide the manner in which this lesion is to be handled, with a prognosis value . A superficial grade (1 or 2a),will require no treatment and it will evolve without sequela . However, upon the determination of deep, ulcerated circumferential lesions, or with necrotic fundus by endoscopy (Grade 2b, and 3), patients shall be hospitalized and shall receive enteral or parenteral nutrition, as well as antibiotic protection . Careful attention should be given due to the risk of perforation or hemorrhage, and ocasionally, urgent surgical treatment will be necessary.The use of corticosteroids has proved to be innefective in preventing stenosis and is potentially dangerous . The most frequent late sequela is the developing of esophageal stenosis (developing in 50-70% of the 2b, and in all of the 3 who survive), and antral stenosis . The esophageal stenosis are tributaries of dilatations with bougies . An option to avoid stenosis, specially in children, is the placement of short plastic tubes, temporarily . In cases where there is no good response to the dilatations . or when the stenosis are long and multiple, surgery with interposition of colon or jejunum will be necessary . Usually, the development of gastric stenosis requires surgery . Motor alterations and gastroesophageal reflux as sequela may also be present, and belatedly, a greater risk to develoop squamous cancer. Clin Exp Pharmacol Physiol, 2002 Oct, 29(10), 880 - 4 Choleresis and inhibition of biliary lipid secretion induced by piperacillin in the rat; Gonzalez P et al.; 1 . The effects of the administration piperacillin on bile flow and biliary lipid secretion were studied in male Wistar rats . 2 . Intravenous injection of piperacillin at doses ranging from 0.3 to 3.0 mmol/kg bodyweight led to an increase in its biliary concentration and excretion rate . Maximal biliary excretion was reached at a dose of 2.0 mmol/kg piperacillin . 3 . Excretion of the antibiotic into bile was associated with a marked choleresis . A linear relationship was observed between bile flow and piperacillin excretion, 5.7 micro L bile being produced per micro mol piperacillin excreted into the bile . 4 . Continuous i.v . infusion of piperacillin at 2.0 mmol/100 g per min did not result in significant changes in bile acid or cholesterol secretion, but biliary phospholipid secretion was markedly reduced . The inhibitory effect on phospholipid secretion was also present when biliary lipid output had been previously increased by an infusion of taurocholate (200 nmol/100 g per min) . Addition of taurocholate did not reverse the impairment of phospholipid secretion induced by piperacillin . 5 . These results indicate that acute administration of piperacillin in the rat induces a marked choleresis by stimulating bile acid-independent bile flow . The significant impairment in phospholipid secretion suggests a specific effect on intracellular supply and/or translocation across the canalicular membrane. Pediatr Pulmonol, 2002 Oct, 34(4), 287 - 96 Effectiveness and tolerability of high-dose salmeterol in cystic fibrosis; Hordvik NL et al.; The efficacy and tolerability of high-dose salmeterol (100 mcg, BID) and albuterol (2.5 mg, BID) were compared with those of albuterol (2.5 mg, BID) in outpatients with cystic fibrosis in a randomized, double-blind, double-dummy, placebo-controlled, crossover study with both short- (4 weeks of each) and long-term (24 weeks of each) treatment periods . The primary outcome measure was the difference in mean change in forced expired volume in 1 sec (FEV(1)) from baseline to the end of each treatment, and secondary measures included changes in forced vital capacity (FVC), forced expiratory flow between 25-75% of FVC (FEF(25-75)), patient-rated weekly symptom scores, number of extra (rescue) albuterol treatments, and number of antibiotic treatments . Tolerability was evaluated by changes in vital signs and adverse events.Thirty-six out of 44 patients enrolled finished the short-term treatment period, and 19 out of 23 who continued the study also finished the long-term treatment period . There was no significant difference in the mean % change in FEV(1) from baseline to completion of 4 weeks with each drug in the short-term treatment period (0.1% vs . 0.06%, albuterol vs . salmeterol; respectively) . In the long-term treatment period, there was a significant decrease from baseline in FEV(1) with albuterol vs . salmeterol, as measured after both 12 and 24 weeks of each treatment (-6.2% vs . 1.8%, P = 0.013 after 12 weeks, and -6.5% vs . 1.7%, P = 0.002, after 24 weeks, respectively) . In both treatment periods, salmeterol was well-tolerated . While there were more rescue treatments per patient per week with albuterol than with salmeterol treatment in both the short- and long-term periods (0.67 vs . 0.40 and 1.76 vs . 0.74, respectively), rescue treatments were needed significantly more often for only the long-term period with albuterol compared to salmeterol (P = 0.022) . Also, there were more antibiotic interventions with albuterol than with salmeterol treatment in both the short- and long-term periods (25 vs . 10 and 56 vs . 42, respectively); however, antibiotics were needed significantly more often for only the short-term period (P = 0.011) . In addition, there was a significantly higher symptom score with albuterol vs . salmeterol treatment during the second half of the long-term period (1.24 vs . 0.89, P = 0.001).In conclusion, long-term high-dose salmeterol was equally safe and was associated with better pulmonary function, fewer interventions, and fewer respiratory symptoms compared to standard therapy with albuterol in a population of outpatients with mild to moderate CF . J Biol Chem, 2002 Nov 8, 277(45), 42633 - 8 Epub 2002 Aug 29. Identification and characterization of tyrosyl radical formation in Mycobacterium tuberculosis catalase-peroxidase (KatG); Chouchane S et al.; The catalytic function of Mycobacterium tuberculosis catalase-peroxidase (KatG) and its role in activation of the anti-tuberculosis antibiotic isoniazid were investigated using rapid freeze-quench electron paramagnetic resonance (RFQ-EPR) experiments . The reaction of KatG with peroxyacetic acid was followed as a function of time using x-band EPR at 77 K . A doublet EPR signal appears within 6.4 ms after mixing and at time points through hundreds of milliseconds . Thereafter, a singlet signal develops and finally predominates after 1 s, with a total yield of radical approximately 0.5 spin/heme . Simulation of the spectra provided EPR parameters consistent with those for tyrosyl radicals . Changes in the hyperfine splitting and/or line width in spectra for l-3,3-{2H2}tyrosine-labeled, but not l-2,4,5,6,7-{2H5}tryptophan-labeled KatG confirmed this assignment . The initial rate of radical formation was unchanged using a 3-fold or 10-fold excess of peroxyacetic acid, consistent with a rate-determining step involving an intermediate . Although Compound I is likely to be the precursor of tyrosyl radical in KatG, neither its EPR signal nor its reduction to Compound II during formation of the radical(s) could be observed . The tyrosyl radical doublet signal was rapidly quenched by addition of isoniazid and benzoic hydrazide, but not by iproniazid, which binds poorly to KatG. Eur J Cardiothorac Surg, 2002 Sep, 22(3), 373 - 6 Intrapericardial fibrinolytic therapy in purulent pericarditis; Ustunsoy H et al.; OBJECTIVE: Purulent pericarditis is a rare disease that is being conventionally managed with intravenous antibiotics and pericardial drainage . In our study, we used intrapericardial fibrinolytic treatment together with pericardiocentesis and antibiotic therapy . We evaluated the role of intrapericardial fibrinolytic treatment in nine purulent pericarditis patients . METHODS: Six children and three adult patients with purulent pericarditis, aged between 5 and 50 years, were treated with intrapericardial fibrinolysis by streptokinase . Intrapericardial drainage catheter was placed into the subxyphoidal localization under local anaesthesia and echocardiography guidance, streptokinase was infused into the pericardial sac as the fibrinolytic agent . RESULTS: Repeat echocardiograms showed no reaccumulation of pericardial effusions, pericardial thickening or constrictions . No patients had systemic bleeding, arrhythmias, or hypotension . There was one death which was due to sepsis and congestive heart failure . CONCLUSION: We believe that early pericardial drainage and intrapericardial fibrinolysis appears to be safe and effective in the treatment of purulent pericarditis. Toxicology, 2002 Sep 30, 179(1-2), 85 - 93 Induction of metallothionein by zinc protects from daunorubicin toxicity in rats; Ali MM et al.; Daunorubicin (DNR) is an anthracyline antibiotic used in the treatment of a variety of human cancers . Reactive oxygen species (ROS) produced in the metabolism of DNR have severe cardiotoxicity which consequently compromises its clinical use as anticancer drug . This study aimed to investigate the effect of DNR administration on both cardiac and hepatic tissues, and the possible protective role of zinc on the cardiotoxicity and hepatotoxicity produced by DNR . Administration of 10 or 20 mg/kg DNR to Sprague-Dawley rats, increases serum creatine kinase activity, and blood troponin T levels (as cardiotoxicity indices), alanine aminotransferase activity (as hepatotoxicity index), as well as cardiac and hepatic 2-thiobarbituric acid reactive substances (as an index of lipid peroxidation) . Treatment with 20 mg/kg Zn prior to DNR, dramatically induced metallothionein-1 (MT-1) mRNA and MT protein in both heart and liver while DNR alone induced MT, but to a much lower degree than Zn . The analysis of MT protein isoforms revealed that MT-1 was the form induced, while metallothionein-2 (MT-2) levels remained practically unchanged . The increases in both MT protein and MT-1 mRNA ran parallel with the reduction of cardiac and hepatic toxicities . Our results indicate that MT induction by Zn is a highly effective approach in preventing cardiotoxicity and hepatotoxicity caused by DNR . These animal data suggest the use of Zn to reduce DNR-induced cardiotoxicity and hepatotoxicity in the chemotherapy of cancer patients. Braz J Infect Dis, 2002 Aug, 6(4), 149 - 56 Epub 2003 Apr 01. Treatment of adults with community-acquired respiratory tract infections: results of a multicentric clinical trial with gatifloxacin; Medeiros EA; Respiratory tract infections have an important clinical and economic impact and they are the most common indication for antibiotic use in outpatient practice . This prospective, multicenter non-controlled trial assessed the efficacy and safety of gatifloxacin in the treatment of community-acquired respiratory tract infections . Patients were treated with a daily oral dose of gatifloxacin 400 mg for 7-14 days . The diagnosis of respiratory infection was made based on the clinical condition and/or radiologic findings . A total of 5,044 adult patients with community-acquired respiratory infections was treated with gatifloxacin in different centers in Brazil between March 1, 2001, and October 31, 2001 . Among the 5,044 patients treated, 1,501 patients (29.76%) had community-acquired pneumonia, 756 (14.99%) had acute exacerbation of chronic bronchitis and 2,787 (55.25%) had acute sinusitis . Of the total of patients treated, 3,607 (71.51%) were considered cured, 1,261 (25%) progressed with some clinical improvement, 28 (0.56%) presented a relapse, 56 (1.11%) failed to treatment and 92 (1.82%) were unable to be evaluated . Adverse events were described in 634 (12.57%) patients . The most common adverse events were: nausea (2.24%); dyspepsia (1.86%); diarrhea (0.79%); change in taste (0.46%); insomnia and irritability (0.22%); dizziness (0.77%); headache (0.42%); allergic reaction (0.18%); Central Nervous System alterations insomnia, agitation, anxiety (0.46%) . This study showed that the treatment of respiratory tract infections with gatifloxacin was safe and efficient and had a low incidence of adverse events. Clin Infect Dis, 2002 Sep 15, 35(6), E60 - 4 Epub 2002 Aug 23. Pythium insidiosum pleuropericarditis complicating pneumonia in a child with leukemia; Heath JA et al.; We describe a 12-year-old boy with acute myeloid leukemia who developed pleuropericarditis while he was neutropenic and was receiving intravenously administered antibiotic and antifungal therapy for pneumonia . A KOH preparation of the purulent material from an extensive diagnostic and therapeutic pleuropericardial drainage procedure revealed multiple irregularly septate hyphae, and cultures yielded the organism Pythium insidiosum . After completing a 12-month course of intravenously administered liposomal amphotericin B (AmBisome; Fujisawa Healthcare) and itraconazole, the patient remained alive, in clinical remission, and symptom free. Radiology, 2002 Sep, 224(3), 852 - 60 Drug-induced pneumonitis: thin-section CT findings in 60 patients; Akira M et al.; PURPOSE: To describe thin-section computed tomographic (CT) findings in patients with drug-induced pneumonitis, to compare these CT findings, and to correlate them with arterial oxygen tension level . MATERIALS AND METHODS: Thin-section CT scans obtained in 60 patients with drug-induced pneumonitis were evaluated retrospectively . The patients had 31 cases of antineoplastic agent-induced pneumonitis and 29 cases of nonneoplastic agent-induced pneumonitis (antibiotic agent, 20 cases; herbal medicine {sho-saiko-to}, four cases; antirheumatic agent, three cases; phenytoin, one case; disodium cromoglycate, one case) . CT scans were reviewed by two chest radiologists in consensus . Correlation between arterial oxygen tension level and the extent of disease at CT was available in 21 patients . These two factors were compared by using the Spearman rank correlation coefficient . RESULTS: The predominant findings in antineoplastic agent-induced pneumonitis were diffuse or multifocal ground-glass opacities with intralobular interstitial thickening . The predominant CT findings in antibiotic agent-induced pneumonitis were patchy ground-glass opacities with centrilobular opacities and interlobular septal lines . The predominant CT findings in herbal medicine-induced pneumonitis were diffuse ground-glass opacities with patchy consolidation . Interlobular septal lines and centrilobular opacities were observed more frequently in antibiotic agent-induced pneumonitis, and intralobular interstitial thickening was observed more frequently in antineoplastic agent-induced pneumonitis . A significant correlation was established between arterial oxygen tension level and extent of disease at CT (r = -0.84, P <.05) . CONCLUSION: In addition to ground-glass opacities and interlobular septal lines, the most common thin-section CT findings were intralobular interstitial thickening, observed in antineoplastic agent-induced pneumonitis, and centrilobular opacities, observed in antibiotic-induced pneumonitis . Copyright RSNA, 2002 J Org Chem, 2002 Sep 6, 67(18), 6361 - 5 Asymmetric synthesis of (+)-negamycin; Jain RP et al.; An asymmetric synthesis of the antibiotic (+)-negamycin (1) has been achieved, starting from commercially available (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (2) . The synthesis involved the stabilized Wittig olefination of the lactone carbonyl group of 2 and subsequent asymmetric hydrogenation to generate the corresponding all-syn oxazine 4 with excellent diastereoselectivity . Conversion of 4 into beta-alkoxy imine 7 and subsequent CeCl3-promoted chelation-controlled allylation of 7 generated the corresponding homoallylamine 8 with good diatereoselectivity, which was readily converted into (+)-negamycin (1) in 25% overall yield over 11 steps. Leukemia, 2002 Sep, 16(9), 1627 - 36 Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin); Larson RA et al.; We analyzed the safety and efficacy of Mylotarg (gemtuzumab ozogamicin, an antibody-targeted chemotherapy consisting of a humanized anti-CD33 antibody linked to calicheamicin, a potent antitumor antibiotic) in the treatment of 101 patients > or =60 years of age with acute myeloid leukemia (AML) in untreated first relapse in three open-label trials . Mylotarg is administered as a 2-h intravenous infusion at 9 mg/m(2) for two doses with 14 days between doses . The overall remission rate was 28%, with complete remission (CR) in 13% of patients and complete remission with incomplete platelet recovery (CRp) in 15% . Median survival was 5.4 months for all patients and 14.5 months and 11.8 months for patients achieving CR and CRp, respectively . CD33 antigen is present on normal hematopoietic progenitor cells; thus, an expected high incidence of grade 3 or 4 neutropenia (99%) and thrombocytopenia (99%) was observed . The incidences of grade 3 or 4 elevations of bilirubin and hepatic transaminases were 24% and 15%, respectively . There was a low incidence of grade 3 or 4 mucositis (4%) and infections (27%) and no treatment-related cardiotoxicity, cerebellar toxicity, or alopecia . Mylotarg is an effective treatment for older patients with CD33-positive AML in first relapse and has acceptable toxicity. Appl Environ Microbiol, 2002 Sep, 68(9), 4472 - 9 Molecular evolution of aromatic polyketides and comparative sequence analysis of polyketide ketosynthase and 16S ribosomal DNA genes from various streptomyces species; Metsa-Ketela M et al.; A 613-bp fragment of an essential ketosynthase gene from the biosynthetic pathway of aromatic polyketide antibiotics was sequenced from 99 actinomycetes isolated from soil . Phylogenetic analysis showed that the isolates clustered into clades that correspond to the various classes of aromatic polyketides . Additionally, sequencing of a 120-bp fragment from the gamma-variable region of 16S ribosomal DNA (rDNA) and subsequent comparative sequence analysis revealed incongruity between the ketosynthase and 16S rDNA phylogenetic trees, which strongly suggests that there has been horizontal transfer of aromatic polyketide biosynthesis genes . The results show that the ketosynthase tree could be used for DNA fingerprinting of secondary metabolites and for screening interesting aromatic polyketide biosynthesis genes . Furthermore, the movement of the ketosynthase genes suggests that traditional marker molecules like 16S rDNA give misleading information about the biosynthesis potential of aromatic polyketides, and thus only molecules that are directly involved in the biosynthesis of secondary metabolites can be used to gain information about the biodiversity of antibiotic production in different actinomycetes. Appl Environ Microbiol, 2002 Sep, 68(9), 4334 - 40 Role of tfxE, but not tfxG, in trifolitoxin resistance; Scupham AJ et al.; Eight genes, tfxABCDEFG and tfuA, confer production of trifolitoxin (TFX), a ribosomally synthesized, posttranslationally modified peptide antibiotic, in TFX-sensitive alpha-proteobacteria . An in-frame deletion in tfxE significantly reduced a strain's resistance to TFX in comparison to that of an otherwise identical construct containing wild-type tfxE . The deletion of tfxG had no effect on TFX resistance . Nevertheless, RNase protection assays showed that tfxE and tfxG are transcribed, showing that the tfxDEFG mRNA was produced on the same transcript . Examination of the role of tfxG in TFX production showed that the tfxG mutant expressed slightly less TFX activity and produced only one TFX isomer while four are produced by the wild-type strain . Thus, tfxE plays an important role in TFX resistance while tfxG is important in optimal TFX production through the production of TFX isomers. Br J Haematol, 2002 Sep, 118(4), 1104 - 11 Influence of post-transplant recombinant human granulocyte colony-stimulating factor administration on peritransplant morbidity in patients undergoing autologous stem cell transplantation; Demirer T et al.; This study evaluated of the effect of post-transplant recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on the parameters of peritransplant morbidity . Three sequential and consecutive cohorts of 20 patients each received either post-transplant rhG-CSF at a dose of 5 micro g/kg/d i.v . in the morning, starting on d 0, d 5, or no rhG-CSF . Patients who received rhG-CSF starting on d 0 and 5 recovered granulocytes more rapidly than those not receiving rhG-CSF (P < 0.001 for ANC >or= 0.5 and 1 x 10(9)/l) . RhG-CSF administration was not significantly associated with more rapid platelet engraftment . RhG-CSF administration starting on d 0 and 5 was significantly associated with a decreased duration of fever (P = 0.002 and 0.001 respectively), antibiotic administration (P < 0.001 and 0.006 respectively) and shorter hospitalization (P < 0.001 and 0.001 respectively) compared with the reference group . There was no difference between the d 0 and d 5 arms regarding the parameters of peritransplant morbidity . In conclusion, rhG-CSF administration was associated with a faster granulocyte recovery, shorter hospitalization, and shorter period of fever and non-prophylactic antibiotic administration . This study also showed that starting rhG-CSF administration on d 5 may be as effective as d 0 on the clinical outcome and may be an economical approach in routine clinical practice in this cost-conscious era. Semin Pediatr Infect Dis, 2002 Jul, 13(3), 174 - 81 Influenza vaccines in children; Neuzil KM et al.; Influenza is a common disease of childhood . Young children and children with high-risk medical conditions are at increased risk of being hospitalized when infected with influenza virus . Children of all ages have excess physician visits and receive excess antibiotic prescriptions during influenza season . The safety, immunogenicity, and efficacy of influenza vaccines in children are described in this review . Clinical trials and postlicensure experience have demonstrated that trivalent inactivated influenza vaccine is well-tolerated in children . Efficacy of the inactivated vaccine also has been demonstrated in numerous clinical trials . In comparison to trivalent inactivated influenza vaccine, investigational cold-adapted, live-attenuated influenza vaccine (LAIV) has the advantage of an intranasal route of administration . A large clinical trial demonstrated the tolerability and efficacy of the trivalent live, attenuated product in children 15 to 71 months of age . Pending information on safety and coadministration of this vaccine with other childhood vaccines will determine if it is licensed and recommended for use in children, including possible expanded indications for routine yearly administration to young children. J Pediatr Orthop, 2002 Sep-Oct, 22(5), 632 - 7 Management of childhood chronic tibial osteomyelitis with the Ilizarov method; Kucukkaya M et al.; The efficacy of the Ilizarov method in the management of the long bone defect is well established . There have been rare reports about the use of the Ilizarov method in the bone defect caused from childhood osteomyelitis . In this article, the authors present results of seven patients with childhood chronic hematogenous osteomyelitis of the tibia who were treated with the Ilizarov method . The treatment protocol also included sequestrectomy and debridement, appropriate antibiotic therapy, and bifocal treatment with the Ilizarov method . The mean age was 7.2 years old (range 6-8) . After sequestrectomy and debridement, all cases were classified as B1 infected pseudoarthrosis according to Paley's criteria . All patients had active infection at the beginning of the treatment . The mean bone defect was 7.4 cm (range 3.5-12) . Follow-up time was 4.6 years (range 2.7-5.8) . At the time of fixator extraction, complete consolidation was obtained in all the patients . Healing index was 32.3 days/cm (range 28-44) . Bone grafting was not required at the docking site in any of the patients . Functional and radiologic results were judged excellent according to Paley's criteria in all patients at the last follow-up . This study indicates that the bifocal method of the Ilizarov treatment is the best alternative for the bone defect caused by chronic hematogenous osteomyelitis in children. East Mediterr Health J, 2000 Sep-Nov, 6(5-6), 1026 - 34 Induction of leukaemia in chloramphenicol-treated toads; el-Mofty MM et al.; Chloramphenicol has been associated with the development of aplastic anaemia . As it is still widely used in Egypt, we studied its effect on 100 Egyptian toads (Bufo regularis) given a dose of chloramphenicol of 5 mg/40 g body weight for 12 weeks . We found it induced numerous, severe ultrastructural changes in almost all types of leukocytes . These changes were similar to those induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene in 100 toads used as the carcinogen control group, and similar to those in leukocytes reported in humans with leukaemia . We recommend regulations be applied on the use of this antibiotic in countries where it is still widely used. Ann Pharmacother, 2002 Sep, 36(9), 1383 - 6 Treatment of azole-resistant oropharyngeal candidiasis with topical amphotericin B; Grim SA et al.; OBJECTIVE: To report a case of successful treatment of azole-refractory oropharyngeal candidiasis with topical amphotericin B . CASE SUMMARY: A 30-year-old white woman presented with recurrent oral thrush . The patient had been exposed to azole antifungals for >20 years, and in vitro susceptibility tests revealed class resistance . The patient started taking amphotericin B 100 mg oral suspension swish-and-spit 4 times daily . After 4 weeks of topical amphotericin B treatment, the patient reported significant symptomatic improvement . The oral candidiasis worsened following a course of oral antibiotics, but improved once the antibiotic was discontinued and after receiving amphotericin B swish-and-swallow for 4 additional weeks . DISCUSSION: Current Infectious Diseases Society of America guidelines include topical amphotericin B as a potentially effective option for the treatment of oropharyngeal candidiasis . There is limited evidence to support this recommendation . Besides lack of data, an appropriate dosing regimen and consistent means of product formulation need to be determined . CONCLUSIONS: This report demonstrates the potential role for topical amphotericin B in the treatment of azole-refractory oral candidiasis . Double-blind, randomized, controlled trials are needed to define dosing, efficacy, administration, and long-term safety of oral amphotericin B. Ann Pharmacother, 2002 Sep, 36(9), 1360 - 5 Empiric carbapenem monotherapy in pediatric bone marrow transplant recipients; Nelson WK et al.; OBJECTIVE: To determine which carbapenem (imipenem/cilastatin or meropenem) was the preferable empiric antibiotic monotherapy in pre-engrafted pediatric bone marrow transplant (BMT) patients in terms of patient tolerance, therapeutic efficacy, and cost . METHODS: We prospectively analyzed 16 pediatric BMT patients who received meropenem, and retrospectively analyzed 16 matched patients who had received imipenem/cilastatin for BMT procedures during the prior 2-year period . We evaluated the patients for evidence of bacterial infection, necessity for concurrent antibiotics, vomiting episodes, duration of concurrent total parenteral nutrition (TPN), and cost of therapy . RESULTS: We found no differences in the number of culture proven or clinically suspected breakthrough bacterial infections or the need for concurrent additional antibiotics between the groups . Our analysis found that patients who received meropenem experienced significantly less vomiting than those in the imipenem/cilastatin cohort . Our data showed both direct and indirect cost savings for the meropenem group . The statistical and clinical differences in the number of vomiting episodes between these groups impacted other aspects of patient care, antiemetic use, and TPN duration . CONCLUSIONS: By switching to meropenem, we reduced the cost of antiemetic therapy per patient treatment course, and also showed a trend toward reduced duration of TPN . We found that meropenem provided both clinical and fiscal advantages over imipenem/cilastatin as empiric antibiotic monotherapy in neutropenic pediatric BMT patients. Scand J Infect Dis, 2002, 34(7), 500 - 4 Hepatocyte growth factor may act as an early therapeutic predictor in pneumonia; Nayeri F et al.; High serum levels of hepatocyte growth factor (HGF) may reflect the regenerative effect and enhanced local and systemic production of this cytokine after organ injuries . The possibility of using serial serum HGF values in order to predict the results of therapy for pneumonia was investigated in this study . In a prospective multicenter study we investigated the serum levels of HGF and CRP before and within 48 h after treatment in 70 patients with pneumonia . Serum levels of HGF before treatment were significantly higher than the HGF levels of a normal population (p < 0.0001) . Within 48 h serum HGF levels had decreased significantly in those patients who ultimately responded to the initial antibiotic therapy (p < 0.0001) . Serum HGF levels at 48 h were unchanged or increased in cases in whom the initial therapy was ineffective and had to be changed . CRP and HGF levels were significantly correlated . Using multivariate logistic regression analysis it was found that individual changes in acute serum HGF levels and serum HGF levels obtained within 48 h could predict the results of therapy at least as significantly (p < 0.003) as CRP (p = 0.05), although CRP levels were known and used by the physician to decide whether or not to change the initial therapy . We conclude that serial control of serum HGF levels can be used as an early indicator to predict the results of therapy during treatment of pneumonia. Radiat Prot Dosimetry, 2002, 99(1-4), 69 - 72 Computer simulation of 57Fe bleomycin auger effects in DNA; Terrissol M et al.; The antibiotic bleomycin binds to the DNA and induces double strand breaks (DSBs) . To increase the cleavages . 57Fe is used to form a complex suitable for Mossbauer effect . The de-excitation of the resonant excited 57Fe nucleus releases Auger electrons and X rays . The goal of this work is to evaluate the increase in yield of DSBs due to the 57Fe, using Monte Carlo simulation methods . Particles spectra and the yields of single strand breaks (SSBs) and DSBs were calculated by considering direct events on DNA and reaction of all radical species generated in the radiolysis of its environment . The Auger spectrum shows a large number of electrons with energies below 100 eV, mainly responsible for direct damage, while another group around 600-700 eV is responsible for indirect damage effects . Bleomycin receives about one fourth of the energy deposited in DNA and an average of 0.65 DSB per de-excitation is observed. Am J Obstet Gynecol, 2002 Aug, 187(2), 268 - 72 Preterm premature rupture of the membranes is associated with a reduction in neonatal respiratory distress syndrome; Sims EJ et al.; OBJECTIVE: The purpose of this study was to evaluate the effect of preterm premature rupture of the membranes on the frequency of respiratory distress syndrome among singleton pregnancies that are complicated with preterm delivery . STUDY DESIGN: We performed a retrospective analysis of singleton pregnancies that were delivered between 24 and 34 weeks of gestation . Patients were categorized on the basis of membrane integrity into two groups: ruptured versus intact . All patients received prophylactic antibiotics and a single course of antenatal betamethasone . Data were analyzed with the Student t test, the chi(2) test, and the Fisher exact test . Multiple logistic regression analysis was performed to examine the effect of possible confounding variables that were considered risk factors for respiratory distress syndrome . Probability values of <.05 for all two-tailed tests were considered significant . RESULTS: A total of 366 patients were included (99 patients in the preterm premature rupture of the membranes group and 267 patients in the intact membranes group) . Patients were delivered at 30.7 +/- 2.9 and 30.1 +/- 2.7 (mean +/- SD) weeks of gestation, with birth weights of 1620 +/- 594 and 1417 +/- 501 g, respectively . The frequency of respiratory distress syndrome in the neonate was significantly lower in the preterm premature rupture of the membranes group than in their intact counterparts (17% vs 39%, P <.001) . Multiple logistic regression analysis confirmed that preterm premature rupture of the membranes (odds ratio, 0.16; 95% CI, 0.08-0.34) was independently associated with a reduction in the frequency of respiratory distress syndrome . CONCLUSION: In the clinical setting of delivery before 34 weeks of gestation, preterm premature rupture of the membranes is associated with a significant decrease in the frequency of neonatal respiratory distress syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2002 Jul, 94(1), 111 - 4 Proliferative periostitis of Garré: Report of a case; Jacobson HL et al.; Proliferative periostitis of Garre is described as a productive and proliferative inflammatory response of periosteum to infection or other irritation . This can be odontogenic or non-odontogenic in nature . This is a case report of an odontogenic periostitis resulting from periapical inflammation of endodontic origin . It was successfully treated by nonsurgical endodontics . Antibiotic therapy was not used during the treatment of this patient. J Bacteriol, 2002 Sep, 184(18), 5113 - 20 Fe(2+)-tetracycline-mediated cleavage of the Tn10 tetracycline efflux protein TetA reveals a substrate binding site near glutamine 225 in transmembrane helix 7; McMurry LM et al.; TetA specified by Tn10 is a class B member of a group of related bacterial transport proteins of 12 transmembrane alpha helices that mediate resistance to the antibiotic tetracycline . A tetracycline-divalent metal cation complex is expelled from the cell in exchange for a entering proton . The site(s) where tetracycline binds to this export pump is not known . We found that, when chelated to tetracycline, Fe(2+) cleaved the backbone of TetA predominantly at a single position, glutamine 225 in transmembrane helix 7 . The related class D TetA protein from plasmid RA1 was cut at exactly the same position . There was no cleavage with glycylcycline, an analog of tetracycline that does not bind to TetA . The Fe(2+)-tetracycline complex was not detectably transported by TetA . However, cleavage products of the same size as with Fe(2+) occurred with Co(2+), known to be cotransported with tetracycline . The known substrate Mg (2+)-tetracycline interfered with cleavage by Fe(2+) . These findings suggest that cleavage results from binding at a substrate-specific site . Fe(2+) is known to be able to cleave amide bonds in proteins at distances up to approximately 12 A . We conclude that the alpha carbon of glutamine 225 is probably within 12 A of the position of the Fe(2+) ion in the Fe(2+)-tetracycline complex bound to the protein. Clin Sci (Lond), 2002 Aug, 103 Suppl 48, 327S - 331S Effects of periodontopathic bacteria on the expression of endothelin-1 in gingival epithelial cells in adult periodontitis; Ansai T et al.; Adult periodontitis, which is the major cause of adult tooth loss, is commonly characterized by chronic inflammatory disease caused by infection with periodontopathic bacteria such as Porphyromonas gingivalis . Our aims in the present study were to examine the expression of endothelin-1 (ET-1) in cultured HEp-2 epithelial cells after infection with P . gingivalis, and in gingival tissue from adult periodontitis patients . The cell lines were infected with the strains P . gingivalis 33277 and 381 for assessment of bacterial invasion using an antibiotic protection assay, and the expression of ET-1, inflammatory cytokines and cell adhesion molecules was examined by ELISA and reverse transcription-PCR . The expression of ET-1, as well as that of interleukin-1 beta, interleukin-8 and ICAM-1 (intercellular cell adhesion molecule 1), was induced significantly in a time-dependent manner, whereas the expression of MCP-1 (monocyte chemotactic protein-1), RANTES (regulated upon activation, normal T-cell expressed and secreted) and VCAM-1 (vascular cell adhesion molecule 1) was not . Furthermore, in gingival tissues from adult periodontitis patients, we also observed increased expression of ET-1 mRNA compared with tissue from normal healthy donors . These results suggest that infection by periodontopathic bacteria up-regulates the expression of ET-1, together with that of inflammatory cytokines and ICAM-1, in gingival epithelial cells, and that ET-1 expression may be closely involved in the regulation of cytokine responses and cell-cell adhesion in adult periodontitis lesions. Sheng Wu Gong Cheng Xue Bao, 2002 May, 18(3), 308 - 12 {Construction of eukaryotic expression vector using neomycin-resistance gene mutant as selectable marker}; Gao C et al.; Neomycin-resistance gene is widely used as a selectable marker in eukaryotic expression vector . It codes neomycin phosphotransferase II (NPT II) which confers resistance to various aminoglycoside antibiotic such as G418 and kanamycine . In this work, by site-directed mutagenesis the neo gene mutant was obtained . The expression vector pmDNA using the neo gene mutant as selectable marker has been constructed . After inserting interest luciferase gene, the expression plasmid pmDNAluc + was stably transfected CHO-K1 cells . As a result, the expression positive ratio reaches to approximate 95% and the ratio of high expression colonies is apparently higher than the controls. Anticancer Drugs, 2002 Aug, 13(7), 685 - 92 Gemtuzumab Ozogamicin (CMA-676, Mylotarg) for the treatment of CD33+ acute myeloid leukemia; Voutsadakis IA; Gemtuzumab Ozogamicin (GO, CMA-676) is a monoclonal antibody against the cellular surface antigen CD33 conjugated with the cytotoxic antibiotic calicheamicin . In the beginning of 2000 it obtained US Food and Drug Administration approval for the treatment of refractory acute myeloid leukemia (AML) expressing CD33 in patients older than 60 years who are not candidates for other chemotherapy . After ligation with the CD33 on the cell surface, GO is internalized and hydrolyzed . Its two components are released into the cytoplasm and calicheamicin enters the nucleus where it associates with the DNA, causing double helix breaks and finally cell death . GO is in general well tolerated . The most frequent adverse effect observed is myelotoxicity, with prolonged neutropenia and thrombocytopenia . Veno-occlusive disease of the liver is a less frequent but severe adverse effect . A phase II study points towards a percentage of overall hematologic response around 30% in the setting of refractory or relapsed disease . Future phase III trials will show the most suitable place of GO in the treatment of AML . J Biol Chem, 2002 Oct 25, 277(43), 40544 - 8 Epub 2002 Aug 16. Concanamycin A, the specific inhibitor of V-ATPases, binds to the V(o) subunit c; Huss M et al.; Vacuolar-type ATPase (V-ATPase) purified from the midgut of the tobacco hornworm Manduca sexta is inhibited 50% by 10 nm of the plecomacrolide concanamycin A, the specific inhibitor of V-ATPases . To determine the binding site(s) of that antibiotic in the enzyme complex, labeling with the semisynthetic 9-O-{p-(trifluoroethyldiazirinyl)-benzoyl}-21,23-dideoxy-23-{(125)I}iodo-concanolide A (J-concanolide A) was performed, which still inhibits the V-ATPase 50% at a concentration of 15-20 microm . Upon treatment with UV light, a highly reactive carbene is generated from this concanamycin derivative, resulting in the formation of a covalent bond to the enzyme . In addition, the radioactive tracer (125)I makes the detection of the labeled subunit(s) feasible . Treatment of the V(1)/V(o) holoenzyme, the V(o) complex, and the V-ATPase containing goblet cell apical membranes with concanolide resulted in the labeling of only the proteolipid, subunit c, of the proton translocating V(o) complex . Binding of J-concanolide A to subunit c was prevented in a concentration-dependent manner by concanamycin A, indicating that labeling was specific . Binding was also prevented by the plecomacrolides bafilomycin A(1) and B(1), respectively, but not by the benzolactone enamide salicylihalamide, a member of a novel class of V-ATPase inhibitors. Therapie, 2002 Mar-Apr, 57(2), 123 - 7 {What are the prospects for pharmacological treatment of prion disease?}; Adjou KT et al.; There is currently no effective therapy available for Creutz-feldt-Jakob disease . However, a limited number of drugs such as polyanions, the amyloid-binding dye Congo red, amphotericin B anthracyclines, dapsone, beta sheet breaker peptides, porphyrines and phtalocyanines have been found to delay the appearance of the clinical signs in experimental prion diseases . Today, the most promising agent would appear to be a less toxic derivative of amphotericin B, MS-8209 . Indeed this compound has a wide spectrum of anti-prion activity and is the only molecule capable of prolonging survival time when treatment is performed in the late stages of infection . This result represents an important step forward in therapeutical approaches of prion diseases and justifies the development of new polyene antibiotic derivatives. Pediatr Nephrol, 2002 Aug, 17(8), 633 - 7 Epub 2002 May 17. Combination of ceftriaxone and acyclovir - an underestimated nephrotoxic potential? Vomiero G, Carpenter B, Robb I, Filler G. Management of meningo-encephalitis often involves the need for antibiotic and antiviral treatment . We report a retrospective analysis over a 6-month period of 17 patients (age range 1-14 years) who were treated with combination therapy of ceftriaxone and acyclovir . Mean acyclovir and ceftriaxone doses were 1,222+/-304 and 2,315+/-509 mg/m(2) per day, respectively . Three patients developed acute renal failure with a peak creatinine of up to 865% above baseline, occurring 2-3 days after starting combination therapy . Patients revealed a tubular proteinuria pattern . Renal biopsy of 1 patient showed a tubulotoxic picture but no evidence of crystals . In 12 of 17 patients (70%) there was a significant increase in serum creatinine . This was significantly greater than literature reports of 16% with acyclovir monotherapy . The degree of renal impairment in our patients correlated significantly with the acyclovir dose, while no correlation was found with the ceftriaxone dose . We conclude that the addition of a second nephrotoxic drug aggravated the extent of renal injury in our patients . The mechanism is tubulotoxicity . Caution should be exercised when using this potentially nephrotoxic cocktail, with clear criteria established for the initiation of combination therapy and close monitoring of serum creatinine. Vet Res Commun, 2002 Jun, 26(4), 255 - 62 Efficacy of sarafloxacin in broilers after experimental infection with Escherichia coli; Chansiripornchai N et al.; Infections of chickens with Escherichia coli serotype O78 can be treated with the antibiotic sarafloxacin . Three experiments were conducted on the administration of this drug to chickens that had been experimentally infected with E . coli . The birds were monitored for 10 days after infection for their average daily gain (ADG) and feed conversion ratio (FCR), and the post-mortem pathology was assessed . In the first experiment, sarafloxacin (20 mg/L, equivalent to 5 mg/kg live weight per day), given in the drinking water for 3 days after infection, led to a reduction in the mortality from 75% to 27%, but the ADG of the treated birds was still less than that of the uninfected controls . In the second experiment, when the sarafloxacin was administered at the same dose in the water but over only 2 h, there was also a considerable reduction in mortality, and the ADG and the FCR also improved significantly . In the third experiment, the dose dependence of the drug was tested . The birds were given 5 and 10 mg/kg per day sarafloxacin in each group, starting within 2 h after infection . This rapid administration of the drug completely prevented mortality, while the ADG and FCR were similar to those of the uninfected controls. Antimicrob Agents Chemother, 2002 Sep, 46(9), 3084 - 7 Comparative evaluation of disk diffusion with microdilution assay in susceptibility testing of caspofungin against Aspergillus and Fusarium isolates; Arikan S et al.; We compared the disk diffusion and broth microdilution methods for susceptibility testing of caspofungin against Aspergillus (n = 78) and Fusarium (n = 22) isolates . Microdilution testing followed the NCCLS M-38P guidelines but was performed in antibiotic medium 3 supplemented to 2% glucose (AM3) . Disk diffusion assays were performed on AM3 agar plates with a 2- micro g caspofungin disk . By both methods, caspofungin showed favorable activity against Aspergillus isolates and no activity against Fusarium isolates . In the disk-based format, intrazonal growth that was not influenced by the drug concentration gradient was consistently observed for all of the Aspergillus isolates tested. Antimicrob Agents Chemother, 2002 Sep, 46(9), 2914 - 9 Characterization of sparsomycin resistance in Streptomyces sparsogenes; Lazaro E et al.; The antitumor antibiotic sparsomycin, produced by Streptomyces sparsogenes, is a universal translation inhibitor that blocks the peptide bond formation in ribosomes from all species . Sparsomycin-resistant strains were selected by transforming the sensitive Streptomyces lividans with an S . sparsogenes library . Resistance was linked to the presence of a plasmid containing an S . sparsogenes 5.9-kbp DNA insert . A restriction analysis of the insert traced down the resistance to a 3.6-kbp DNA fragment, which was sequenced . The analysis of the fragment nucleotide sequence together with the previous restriction data associate the resistance to srd, an open reading frame of 1,800 nucleotides . Ribosomes from S . sparsogenes and the S . lividans-resistant strains are equally sensitive to the inhibitor and bind the drug with similar affinity . Moreover, the drug was not modified by the resistant strains . However, resistant cells accumulated less antibiotic than the sensitive ones . In addition, membrane fractions from the resistant strains showed a higher capacity for binding the drug . The results indicate that resistance in the producer strain is not connected to either ribosome modification or drug inactivation, but it might be related to an alteration in the sparsomycin permeability barrier. Org Lett, 2002 Aug 22, 4(17), 2893 - 5 Synthesis of tyrocidine A and its analogues by spontaneous cyclization in aqueous solution; Bu X et al.; {reaction: see text} Head-to-tail cyclization of peptides is a multistep process involving tedious C-terminal activation and side chain protection . Here we report a facile, quantitative cyclization method in aqueous ammonia solution for the total syntheses of the cyclic decapeptide antibiotic Tyrocidine A and its analogues from their fully deprotected linear thioester precursors on a solid support . This novel aqueous method is conformation-dependent and may be applicable to syntheses of other natural cyclic peptides. Rev Gastroenterol Peru, 1999 Oct, 19(4), 273 - 283 {ENTERAL NUTRITION IN PERU}; Ferreyra M et al.; Drawbacks of Nutritional Support diffusion in Peru are presented within current Latin-American technological reality . That reality is compared to widespread use of antibiotic therapy versus a marked lack of use of Nutritional Support . Those factors are against immunity of seriously compromised patients as Enteral Nutrition has positive effects on a patient s immunity.Four patients treated with three kinds of enteral formulas during a prospective study serve as examples to show the suitable consequences of using Enteral Nutrition and why Nutritional Support should be legally enforced and regulated in Peru. Tohoku J Exp Med, 2002 May, 197(1), 47 - 53 Nonsurgical treatment for odontogenic maxillary sinusitis using irrigation through the root canal: preliminary case report; Iikubo M et al.; As a new nonsurgical treatment for odontogenic maxillary sinusitis (OMS), irrigation of the maxillary sinus through the root canal of the causal tooth was carried out to the patient with OMS that had proved refractory to conservative treatments (i.e., root-canal treatment of the causal tooth and antibiotic therapy) . Clinical signs, symptoms, and radiographs before and after the new treatment revealed evidence of good healing . The clinical signs and symptoms, such as oppressive pain in the cheek and retrorhinorrhoea, entirely disappeared immediately after the irrigation (which was done only once) without pain, and the obstructed ostiomeatal unit was aerated on the follow-up CT images . There was no side effect associated with saline irrigation, nor any recurrence of symptoms since the irrigation . We therefore propose the irrigation through the root canal of the causal tooth as a new treatment for periapical disease-induced maxillary sinusitis, a technique that should ensure proper ventilation and drainage by relieving obstruction of the ostiomeatal unit. Sante Salud . 1994 Spring;(4):14. CHWs trained in ARI management; Charleston R et al.; Regular supervision and refresher trainings were the key to the success of a CHW (community health worker) training program in rural Bolivia . Since 1988, with the support of PLAN International, volunteer CHWs have been trained in 115 villages in Sucre, a rural health area lacking adequate health centers . CHWs educate the community, diagnose and treat pneumonia and refer severe cases to health centers or hospitals . CHWs who were already working on diarrheal disease control were chosen for the acute respiratory infection (ARI) case management training . A 3-day training program was organized for individual CHWs in their own homes and communities . The course included practicing on real ARI cases under the trainer's supervision . Since the program started, community respect for CHWs has risen . In one remote village, community leaders reported a marked improvement in child survival . Factors which explain the positive effects of CHWs include: a limited number of clearly defined tasks, provision of one-on-one appropriate training, periodic refresher courses, and continuous supervision . The main problems have been a lack of constant supply of essential drugs and some CHWs over-diagnosing pneumonia . However, once diagnosis is made, CHWs are careful about giving the correct antibiotic doses and instructions to mothers . Refresher training and supervision have helped to correct these initial problems . PLAN International and the Ministry of Health have organized supervision and training meetings every 2 months . The CHWs bring to these meetings reports of children treated and referred . Case management is analyzed, resupply of essential medicines is arranged and those with special problems are scheduled for a supervisory visit . full text Sex Planeam Fam, 1995 Oct-Dec, 8(2), 16 - 8 {Non-contraceptive benefits of contraception}; Costa FJ; PIP: The general benefits of the use of methods of contraception are the documented decrease of maternal and fetal mortality and morbidity, the diminution of the rate of prematurity and low birth weight, the decrease in induced abortion and sexually transmitted diseases (STDs) and certain gynecological cancer types . Natural methods of contraception pose the benefit of lacking effects on the organs and not introducing any external factors into the body . Barrier methods provide protection against STDs (a 50% reduction) and against cervical cancer (human papilloma virus), especially for adolescents and those with multiple sex partners . The chemical methods provide local antiseptic and antibiotic action that can be beneficial for vaginal and cervical infections . Hormonal methods, namely the oral contraceptive (OC) pill, also possess noncontraceptive benefits: regulation of the menstrual cycle, including diminution of dysmenorrhea, menstrual pain, menstrual flow, and anemia; reduced risk of pelvic inflammatory disease, endometrial and ovarian cancer, benign breast pathology, acne, and hirsutism; in addition to the therapy of polycystic ovarian syndrome, hypothalamic amenorrhea, and dysfunctional hemorrhage . Further benefits include the decrease of the risk of osteoporosis, rheumatoid arthritis by 60% in families at risk, ectopic pregnancy, atherosclerosis, uterine myomas by up to 31%, and ovarian cysts . Contraceptives that contain progestational hormones (oral, injectable, implant, or IUD forms) are also beneficial for endometrial hyperplasia and uterine polyps . IUDs (except for progestational IUDs) have local effect without the potential side effects of hormones . Terminal methods of contraception (tubal ligation and ligation of the vas deferens) are reliable without causing alterations in the physiology of the organs . Surg Neurol, 2002 Jun, 57(6), 411 - 3; discussion 413-4 Osteochondroma of the cervical spine--a surprising finding in a liver transplanted patient with polyneuropathy and polyradiculitis: case report; Kroppenstedt SN et al.; BACKGROUND: Osteochondroma of the spine is a rare condition . We report a case of a patient with a cervical osteochondroma presenting with a polyneuropathy and polyradiculitis simultaneously . CASE DESCRIPTION: In a liver-transplant patient with progressive neurological deficits a polyneuropathy and a polyradiculitis were diagnosed . Eventually the patient became quadraparetic and an osteochondroma compressing the cervical spinal cord was found . The patient's neurological symptoms markedly improved after gross total tumor resection and antibiotic therapy . CONCLUSIONS: Review of the literature reveals this case to be an unusual presentation of a cervical osteochondroma, its diagnosis being delayed because of concomitant neurological diseases. Mutat Res, 2002 Aug 29, 505(1-2), 43 - 50 Effect of recombinant interferon-alpha on bleomycin-induced chromosome damage in hamster cells; Bolzan AD et al.; The effect of recombinant interferon-alpha-2a (rIFN-alpha-2a) on the induction of chromosomal aberrations (CAs) by the radiomimetic antibiotic bleomycin (BLM, 5 microg/ml, 30 min, 37 degrees C) in Chinese hamster ovary (CHO) cells was investigated . Recombinant IFN-alpha-2a (4500-180,000IU/ml) was added to the cell cultures 0.5 or 24h before BLM (and left in the culture medium until the end of treatments) or immediately after BLM treatment (and left in the culture medium until harvesting) . Cells were sampled at 18 or 2.5h after the end of treatments, in order to determine, respectively, the effect of rIFN-alpha-2a on the total chromosome damage induced by BLM and on the chromosome damage induced by this antibiotic in the G(2) phase of the cell cycle . A statistically significant increase in the frequency of CAs was observed following treatment with BLM (P<0.05), whereas treatments with rIFN-alpha-2a alone did not produce any significant increase of CAs over control values (P>0.05) . The yield of CAs by BLM was significantly inhibited by rIFN-alpha-2a (P<0.05, 65.3% maximum inhibition) . A strong inhibitory effect (around 80%) of rIFN-alpha-2a on the yield of BLM-induced CAs in the G(2) phase of the cell cycle was also observed . It is suggested that the inhibitory effect of rIFN-alpha-2a on the induction of CAs by BLM is mainly due to the stimulation of DNA synthesis and repair by the cytokine. Klin Oczna, 2002, 104(2), 96 - 8 {Simultaneous bilateral cataract surgery with PC IOL implantation}; Synder A et al.; PURPOSE: To evaluate results of simultaneous bilateral extracapsular cataract extraction with PC IOL implantation and to discuss indications for such treatment . MATERIAL AND METHODS: Simultaneous bilateral cataract surgery was performed in 3 patients: 56-year-old woman with Little's syndrome, 75-year-old woman with Parkinson's disease and 29-year-old mentally handicapped man . All patients required general anesthesia because of the general state of health . All patients were treated topically with broad-spectrum antibiotic drops before the surgery . Simultaneous bilateral surgery was performed as two separate operations . After successful completion of surgery of the first eye, the gloves, drapes and gowns were changed and the new set of instruments and irrigation solution was used . RESULTS: The visual acuity improved in all eyes after surgery, and it was 6/6 in both eyes in patients 1 and 3, whereas it was 6/8 and 6/60 in patient 2, due to glaucomatous optic nerve atrophy . There were no intra- or postoperative complications . CONCLUSIONS: Simultaneous bilateral cataract surgery is a safe procedure if all special conditions are fulfilled . It is specially indicated in patients requiring general anesthesia . Patients are not at risk of the second general anesthesia and achieve earlier visual binocular rehabilitation . Extracapsular cataract extraction with PC IOL implantation was performed in all eyes . The excision of fibrotic anterior lens capsule was necessary before the aspiration of cortical material in 2 eyes with congenital cataracts . The corneal incision and plastic surgery of the iris was done in the eye, which had undergone iridencleisis . In the other eye of the same women cutting and suturing of the iris was performed because of posterior synechiae and very narrow pupil. Arch Esp Urol, 2002 Jun, 55(5), 552 - 5 {{Primary psoas abscess . Presentation of 3 cases}; Capitan Manjon C et al.; OBJECTIVE: To present 3 cases of primary abscess of the psoas muscle . The clinical features, diagnostic tests, treatment and outcome are discussed . METHODS/RESULTS: Three patients that presented with fever and pain referred to the renal and/or iliac fossa are described . Physical examination showed psoas involvement in only one patient . Among the complementary tests performed, ultrasound demonstrated the abscess in one of the cases; the definitive diagnosis was made by contrast-enhanced CT . One of the cases was treated only with antibiotics while the other two cases were treated with CT-guided percutaneous drainage and appropriate antibiotic therapy . CONCLUSIONS: Psoas abscess is an uncommon pathology whose presenting features are usually unspecific . CT with contrast enhancement is considered to be the technique of choice for the diagnosis and to corroborate the resolution of the condition . Recently, the use of CT or US-guided percutaneous drainage has replaced surgery as the initial therapeutic approach for this condition. Int J Obes Relat Metab Disord, 2002 Sep, 26 Suppl 3, S3 - 8 Beyond diabetes: saving lives with insulin in the ICU; Van den Berghe G; The risk of mortality or significant moridity is high among long-stay intensive care unit (ICU) patients . Sepsis, polyneuropathy and multiple organ failure are prominent causes of mortality and morbidity in the ICU . Many ICU patients are hyperglycaemic, presumably reflecting an adaptive development of insulin resistance . We hypothesized that this hyperglycaemia predisposes patients to many of the typical ICU complications, prolonged intensive care dependence and excess mortality . Insulin therapy directed at establishing normoglycaemia was investigated in a series of 1548 ICU patients . An intensive treatment group received insulin infusion tailored to control blood glucose levels in the range 4.4-6.1 mmol/l (80-110 mg/dl), whereas the conventional treatment group only received insulin when glucose levels exceeded 11.1 mmol/l (200 mg/dl) and in that event were maintained in a target range of 10.0-11.1 mmol/l (180-200 mg/dl) . Intensive management of blood glucose levels was reflected in a 43% reduction in intensive care mortality risk (P=0.036 after correction for interim analyses) and a 34% reduction in hospital mortality (P=0.01) . A reduced risk of infection was reflected in a 46% reduction in the risk of septicaemia (P=0.003) and a 35% reduction in the need for prolonged (>10 d) antibiotic therapy (P<0.001) . Regression analysis suggests that control of glucose levels, rather than insulin administration itself, was responsible for the clinical benefits observed . Use of insulin infusion to control glucose levels in ICU patients, at least in populations similar to those in our study, can be expected to achieve clinically welcome improvements in outcome . An algorithm is proposed for implementing this . Further data are needed to establish the applicability of this strategy to other patient groups in the ICU and in general hospital care. Vet Dermatol, 2002 Aug, 13(4), 195 - 202 Putative drug-related pemphigus foliaceus in four dogs; White SD et al.; Four dogs developed cutaneous lesions following the administration of various antibiotics . Histopathology of the lesions was compatible with pemphigus foliaceus, although apoptotic cells suggestive of erythema multiforme were seen in two cases . In two dogs the lesions resolved after 7.5-8.5 months of immune-suppressive treatment . No recurrence was seen during the follow-up period (3 and 4.5 years) . The lesions in the other two dogs resolved within 3 weeks to 3 months following discontinuation of the antibiotic . No recurrence of clinical signs occurred during the follow-up period (1 and 4 years, respectively). Clin Infect Dis, 2002 Sep 1, 35(5), e43 - 9 Epub 2002 Aug 02. Disseminated acanthamebiasis in a renal transplant recipient with osteomyelitis and cutaneous lesions: case report and literature review; Steinberg JP et al.; Disseminated acanthamebiasis is a rare disease that occurs predominantly in patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome but also in immunosuppressed transplant recipients . Few reports have focused on non-HIV-infected patients, in whom the disease is more likely to go unsuspected and undiagnosed before death . We describe a renal transplant recipient with Acanthamoeba infection and review the literature . The patient presented with osteomyelitis and widespread cutaneous lesions . No causative organism was identified before death, despite multiple biopsies with detailed histological analysis and culture . Disseminated Acanthamoeba infection was diagnosed after death, when cysts were observed in histological examination of sections of skin from autopsy, and trophozoites were found in retrospectively reviewed skin biopsy and surgical bone specimens . In any immunosuppressed patient, skin and/or bone lesions that fail to show improvement with broad-spectrum antibiotic therapy should raise the suspicion for disseminated acanthamebiasis . Early recognition and treatment may improve clinical outcomes. Clin Infect Dis, 2002 Sep 1, 35(5), 547 - 55 Epub 2002 Aug 07. Historical changes in pneumococcal serogroup distribution: implications for the era of pneumococcal conjugate vaccines; Feikin DR et al.; Of the 90 pneumococcal serotypes, the 7 in the licensed pneumococcal conjugate vaccine (Prevnar) currently account for >80% of invasive pneumococcal infections among children in the United States . Our objective was to document and explain the changes in pneumococcal serogroup distribution in the United States during the last century . We evaluated temporal trends in the serogroup distribution, using linear regression . Between 1928 and 1998, the proportion of pneumococcal infections caused by the 7 serogroups in the conjugate vaccine increased significantly, from 15% to 59%, in 13 adult studies, and from 53% to 87%, in 19 pediatric studies . The proportion of infections caused by the "epidemic" serogroups (1-3 and 5) decreased significantly, from 71% to 7%, in the adult studies, and from 18% to 2%, in the studies of children . These historical trends in serogroup distribution may be explained by changes in antibiotic use, socioeconomic conditions, the immunocompromised status of populations, and blood-culturing practices. Childs Nerv Syst, 2002 Jul, 18(6-7), 340 - 3; discussion 344 Epub 2002 May 30. Bifrontal decompressive craniectomy for acute subdural empyema; Ong YK et al.; INTRODUCTION: Subdural empyema is an uncommon but serious complication of sinusitis . Despite the use of advanced imaging facilities, modern antibiotic therapy and aggressive neurosurgical protocols, this condition still carries significant morbidity and mortality . CASE REPORT: We report an unusual case of sinusitis-associated acute subdural empyema in a 13-year-old patient, presenting in a catastrophic manner with acutely raised intracranial pressure . Emergency bifrontal decompressive craniectomy was necessary both to reduce the intracranial pressure and to drain the subdural empyema . RESULTS: The full range of intracranial complications subsequently occurred, including brain abscesses, recurrent subdural empyema and ventriculitis . Despite this, the patient's outcome was good, with minimal intellectual deficits . CONCLUSION: In cases of severe intracranial infection, we therefore advocate an aggressive surgical approach coupled with appropriate antibiotics to ensure a good outcome. Anticancer Drugs, 2002 Jul, 13(6), 595 - 8 Down-regulation of telomerase activity by anticancer drugs in human ovarian cancer cells; Kunifuji Y et al.; Maintenance of telomere length is crucial for survival of cells . Telomerase, an enzyme that is responsible for elongation of shortened telomeres, is active in human germ cells as well as most tumor tissues and experimentally immortalized cells . In contrast, most mature somatic cells in human tissues express undetectable or low telomerase activity, implying the existence of a stringent and negative regulatory mechanism . In this study we report the effects of anticancer drugs on telomerase activity in human cancer cells . In assaying for telomerase activity, we basically followed the original TRAP assay system, but with some modifications . A down-regulation of telomerase activity was found when cells of a human ovarian cancer cell line, A2780, were treated with;cis-diamminedichloroplatinum(II) (CDDP; cisplatin) . However, down-regulation of telomerase activity was not found in cells of a cisplatin-resistant cell line, A2780CP, treated with cisplatin . On the other hand, telomerase activity in both the cell lines A2780 and A2780CP was reduced when A2780 or A2780CP was treated with adriamycin, an anthracycline antibiotic having a broad spectrum of antineoplastic activity . The different effects on the telomerase activity of the two types of anticancer drugs may be due the distinct chemical functions of these drugs . The present results may indicate a positive relationship between anticancer effects and down-regulation of telomerase activity by anticancer drugs. J Orthop Trauma, 2002 Aug, 16(7), 484 - 90 The effect of time to definitive treatment on the rate of nonunion and infection in open fractures; Harley BJ et al.; OBJECTIVES: To determine the association between time to definitive surgical management and the rates of nonunion and infection in open fractures resulting from blunt trauma . To determine the association of other clinical determinants with these same adverse events . DESIGN: Retrospective review of a consecutive series of open long bone fractures . SETTING: Referral trauma center with transport times often extending beyond eight hours from the time of injury . PATIENTS: A total of 227 skeletally mature patients with 241 open long bone fractures were treated between January 1996 and December 1998; 215 fractures were available for review at a minimum of twelve months postinjury . INTERVENTION: Medical charts of all patients were reviewed using a standardized data collection form . All available records and radiograph reports were inspected . All cases were followed to clinical and radiographic union of the fracture or until a definitive procedure for nonunion or deep infection was carried out . MAIN OUTCOME MEASURES: Occurrence of deep infections or nonunions after fracture treatment . RESULTS: The mean time to definitive treatment was eight hours and twenty-five minutes (range 1 hour 35 minutes to 30 hours 40 minutes) . Forty patients went on to nonunion, and twenty developed a deep infection . In the final multivariate regression model, time was not a significant factor in predicting either nonunion or infection (p > 0.05) . The strongest determinants for nonunion were found to be presence of infection and grade of injury (p < 0.05) . The strongest predictors for the development of a deep infection were fracture grade and a lower extremity fracture (p < 0.05) . CONCLUSIONS: The risk of developing an adverse outcome was not increased by aggressive debridement/lavage and definitive fixation up to thirteen hours from the time of injury when early prophylactic antibiotic administration and open fracture first aid were instituted. Chest, 2002 Aug, 122(2), 612 - 7 Influence of deviation from guidelines on the outcome of community-acquired pneumonia; Menendez R et al.; STUDY OBJECTIVE:s: Consensus guidelines for the empirical treatment of community-acquired pneumonia (CAP) have been published . We investigated the following factors: (1) the degree of adherence to American Thoracic Society (ATS) and the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) guidelines; and (2) the influence of adhering to these guidelines on mortality and length of hospitalization . DESIGN: Prospective, observational study . SETTING: Tertiary-care teaching hospital . PATIENTS: Two hundred ninety-five patients with CAP who were consecutively admitted to the hospital and treated empirically . INTERVENTIONS: Patients were stratified according to the prognostic rule of Fine, and the antibiotic regimen prescribed in the first 24 h was evaluated as to whether or not it adhered to treatment guidelines . RESULTS: Adherence to SEPAR and ATS guidelines was 66% and 88%, respectively . There were no significant differences in mortality or duration of hospitalization between adherent and nonadherent regimens . However, mortality in severe CAP (Fine risk class V) was significantly higher in patients with nonadherent treatments (SEPAR: relative risk {RR}, 2.6; 95% confidence interval {CI}, 1.1 to 5.6; ATS: RR, 2.5; 95% CI, 1.1 to 5.8) . In a multivariate analysis, adherence to ATS guidelines was independently associated with decreased mortality (RR, 0.3; 95% CI, 0.14 to 0.9) after adjusting for the Fine score . CONCLUSIONS: Adherence was higher to ATS guidelines than to SEPAR guidelines . Severe CAP had a significantly higher mortality when the guidelines (both ATS and SEPAR) were not followed . Length of hospitalization was similar irrespective of adherence to either set of guidelines. Curr Pharm Des, 2002, 8(19), 1749 - 64 Monoclonal antibody-based therapy strategies: providing options for the cancer patient; Milenic DE; Treatment of patients with unconjugated MAb such as rituximab (Rituxan) the anti-CD20 MAb or trastuzumab (Herceptin) the anti-Her2 MAb, have shown efficacy in clinical trials and have gained approval from the Food and Drug Administration (FDA) has a result . Likewise, an anti-CD33 MAb conjugated with the antibiotic calicheamicin (Mylotarg) has proven efficacious in the treatment of patients with acute myeloid leukemia and has also been approved by the FDA . This overview presents some of the monoclonal antibody (MAb)-guided strategies with a focus on some of the experiences reported for MAb evaluated in clinical trials. Curr Pharm Des, 2002, 8(23), 2033 - 48 Selective inhibition of osteoclast vacuolar H(+)-ATPase; Farina C et al.; The proton pump expressed on the plasma membrane of bone resorbing osteoclasts, and which mediates the acidification of the extracellular environment in resorption lacuna, belongs to the family of vacuolar H(+)-ATPases, which are enzymes ubiquitously distributed among all cells and are evolutionary conserved . These pumps have two functional domains: a peripherally associated cytoplasmatic section, and a proton channel composed of several subunits one of which, the 116 kDa subunit, is expressed exclusively in osteoclasts and confers unique functional and pharmacological properties to the osteoclast V-ATPase . It was demonstrated that inhibition of this pump can abolish bone resorption; therefore, osteoclast-selective inhibitors could provide novel and useful agents for the treatment of osteoporosis . This paper reviews the medicinal chemistry approaches that have allowed to obtain such new agents, most of which have been designed starting from the natural macrolide antibiotic bafilomycin A(1), a potent and selective inhibitor of all V-ATPases . Identification of SAR and of minimal structural requirements for bafilomycin activity have allowed to obtain (2Z,4E)-5-(5,6-dichloroindolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (SB-242784) which inhibits the osteoclastic proton pump and bone resorption in vitro . Although it inhibits the activity of non-osteoclastic proton pumps as well, it appears to have reasonable selectivity and its administration for 6 months prevented the loss of femoral and vertebral BMD in ovariectomized rats, without any significant renal effects in control and acid-loaded animals . Other independent approaches that did not start from bafilomycin have led to the discovery of a different class of V-ATPase inhibitors, among which 4-(2,6-dichlorobenzoyl)amino-2-trifluoromethyl(benzoimidazol-1-yl)acetyl morpholine (FR177995) was the most effective in preventing bone resorption in an ovariectomized rat model of osteoporosis . These compounds are of great pharmaceutical and medical interest because they allow to target a specific function of the osteoclast; however, only clinical trials might demonstrate whether they have significant advantages over other inhibitors of bone resorption for the treatment of osteoporosis. J Neurochem, 1976 Nov, 27(5), 1119 - 24 Inhibition by neomycin of polyphosphoinositide turnover in subcellular fractions of guinea-pig cerebral cortex in vitro; Schacht J; The addition of 10(-5) M to 10(-3) M neomycin to incubations of subcellular fractions of guineapig cerebral cortex increased the labelling of phosphatidylinositol phosphate and decreased the labelling of phosphatidylinositol diphosphate by {gamma-32P}ATP . The effect was observed in all subcellular fractions tested and depended on the cationic form of the antibiotic . Similar effects on lipid labelling were exerted by related aminoglycosidic antibiotics, by neamine, spermine and poly-L-lysine . Other neomycin fragments, antibiotics, local anesthetics or small polyamines were ineffective . Neomycin also inhibited the enzymatic hydrolysis of 32P-polyphosphoinositides . The addition of the drug to aqueous dispersions of these lipids increased the turbidity and lowered the pH of the suspensions . It is suggested that the effects of neomycin on polyphosphoinositide metabolism result from the formation of an ionic complex between the lipids and the antibiotic. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2002 Aug, 19(4), 285 - 9 {Conditional targeting of p16(INK4a)exon 1a in mouse embryonic stem cells}; Gong Z et al.; OBJECTIVE: To study the relationship between targeting vector structure and homologous recombination rate and investigate whether the mouse p16(INK4a) plays a role in tumor suppression . METHODS: A conditional targeting vector with 2.0 kb EcoR I/Xba I fragment as short arm and 5.9 kb SpeI/NotI fragment as long arm was built . Of the 2 direct locus crossing- over(loxPs) in the vector, one was inserted at 240 bp upstream of the initiate code of p16(INK4a) exon 1a and the other at 1633 bp downstream of the initiate code . Both exon 1a and the selection marker Neo will be deleted in targeted cells when mediated by Cre . After linearlization and purification, t he targeting vector was introduced into ES cells through electroporation . RESULTS: Twenty-four G418- and gancyclovir-resistant ES cell colonies were picked out and one of them was confirmed as positive by Southern hybridization . CONCLUSION: Targeting vectors with 2 TK genes flanking the homologous arms are likely to produce good result of homologous recombination. Am J Surg, 2002 Aug, 184(2), 148 - 53 Can failure of percutaneous drainage of postoperative abdominal abscesses be predicted? Benoist S, Panis Y, Pannegeon V, Soyer P, Watrin T, Boudiaf M, Valleur P. BACKGROUND: Percutaneous drainage (PD) of complex postoperative abscesses associated with a variety of factors such as multiple location or enteric fistula remains a matter of debate . Accordingly, this retrospective study was designed to determine the predictive factors for failure of PD of postoperative abscess, in order to better select the patients who may benefit from PD . METHODS: From 1992 to 2000, the data of 73 patients who underwent computed tomography (CT)-guided PD for postoperative intra-abdominal abscess, were reviewed . PD was considered as failure when clinical sepsis persisted or subsequent surgery was needed . The possible association between failure of PD and 27 patient-, abscess-, surgical-, and drainage-related variables were assessed using univariate and multivariate analysis . RESULTS: Successful PD was achieved in 59 of 73 (81%) patients . The overall mortality was 3% but no patient died after salvage surgery . Multivariate analysis showed that only an abscess diameter of less than 5 cm (P = 0.042) and absence of antibiotic therapy (P = 0.01) were significant predictive variables for failure of PD . CONCLUSIONS: CT-guided PD associated with antibiotic therapy could be attempted as the initial treatment of postoperative abdominal abscesses even in complex cases such as loculated abscess or abscess associated with enteric fistula. J Orthop Res, 2002 Jul, 20(4), 643 - 7 The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets; Nelson CL et al.; Calcium sulfate was used as a biodegradable delivery system for the administration of antibiotics in musculoskeletal infection . New Zealand white rabbits were infected with Staplylococcus aureus, debrided, and randomized to one of four treatment groups: calcium sulfate pellets with 10% tobramycin sulfate, placebo calcium sulfate pellets and IM tobramycin, placebo calcium sulfate pellets, or debridement . Serum and wound exudate tobramycin concentrations and serum calcium levels were measured . Radiographs, cultures, and histology were analyzed for efficacy and treatment . Rabbits treated with 10% tobramycin sulfate pellets showed a significantly higher eradication of infection (11/13) than rabbits treated with debridement only (5/12), placebo pellets and IM tobramycin (5/14) . or placebo pellets (3/13) . In the group receiving 10% tobramycin sulfate pellets, serum tobramycin concentrations peaked 3 h post-operatively at 5.87 microg/ml and were non-detectable after day 1 . In the group receiving placebo pellets and IM tobramycin, serum concentrations peaked at 7.82 microg/ml 1 h post-operatively, fell to 6.12 microg/ml on day 2, and averaged 4.18 microg/ ml for the remainder of the treatment period . The wound exudate tobramycin concentrations in the animals treated with tobramycin sulfate pellets peaked at 11.9 mg/ml on day 1 and dropped to 2.5 microg/ml on day 7 . There was no significant difference in the serum calcium levels in any of the treatment groups . Calcium sulfate containing tobramycin sulfate has potential utility as a biodegradable local antibiotic delivery system in the treatment of musculoskeletal infections. J Am Chem Soc, 2002 Aug 14, 124(32), 9476 - 88 Total synthesis of deamido bleomycin a(2), the major catabolite of the antitumor agent bleomycin; Zou Y et al.; Metabolic inactivation of the antitumor antibiotic bleomycin is believed to be mediated exclusively via the action of bleomycin hydrolase, a cysteine proteinase that is widely distributed in nature . While the spectrum of antitumor activity exhibited by the bleomycins is believed to reflect the anatomical distribution of bleomycin hydrolase within the host, little has been done to characterize the product of the putative inactivation at a chemical or biochemical level . The present report describes the synthesis of deamidobleomycin demethyl A(2) (3) and deamido bleomycin A(2) (4), as well as the respective aglycones . These compounds were all accessible via the key intermediate N(alpha)-Boc-N(beta)-{1-amino-3(S)-(4-amino-6-carboxy-5-methylpyrimidin-2-yl)propion-3-yl}-(S)-beta-aminoalanine tert-butyl ester (16) . Synthetic deamido bleomycin A(2) was shown to be identical to the product formed by treatment of bleomycin A(2) with human bleomycin hydrolase, as judged by reversed-phase HPLC analysis and (1)H NMR spectroscopy . Deamido bleomycin A(2) was found to retain significant DNA cleavage activity in DNA plasmid relaxation assays and had the same sequence selectivity of DNA cleavage as bleomycin A(2) . The most significant alteration of function noted in this study was a reduction in the ability of deamido bleomycin A(2) to mediate double-strand DNA cleavage, relative to that produced by BLM A(2). J Med Chem, 2002 Aug 15, 45(17), 3630 - 8 Design, synthesis, and biological activity of hybrid compounds between uramustine and DNA minor groove binder distamycin A; Baraldi PG et al.; The design, synthesis, characterization, DNA binding properties, and cytotoxic activity of a novel series of hybrids, namely, a molecular combination of the natural antibiotic distamycin A and the antineoplastic agent uramustine, are reported, and the structure-activity relationships are discussed . This homologous series 29-34 consisted of the minor groove binder distamycin A joined to uramustine (uracil mustard) by suitable aliphatic carboxylic acid moieties containing a flexible polymethylene chain that is variable in length {(CH(2))(n)(), where n = 1-6) . All the hybrid compounds in this series exhibit enhanced activity compared to both distamycin A and uramustine derivatives 22-27 used for conjugation, giving IC(50) values in the range 7.26-0.07 microM following a 1 h exposure of human leukemic K562 cells, with maximal activity shown when n = 6 . The distance between the uramustine and distamycin frame is crucial for the cytotoxicity, with compounds having linker lengths of four to six being at least 20-fold more cytotoxic than linker lengths one to three . Taq polymerase stop experiments demonstrated selective covalent binding of uramustine-distamycin hybrids to A/T rich DNA sequences, which was again more efficient with compounds 32-34 with a longer linker length . Two consequences can be derived from our study: (a) the distamycin moiety directs binding to the minor groove of A/T rich DNA sequences and, consequently, is responsible for the alkylation regioselectivity found in footprinting studies; (b) the higher flexibility due to a longer linker between the distamycin and uracil moieties allows the formation of complexes with the mustard moiety situated more deeply in the minor groove and, hence, with better alkylating properties. Commun Dis Public Health, 2002 Jun, 5(2), 147 - 50 Audit of turnaround times for processing Mycobacterium tuberculosis specimens in a district general hospital; Davies AP et al.; Automated liquid culture systems, coupled with molecular techniques, have decreased the time required for culture, identification and antibiotic susceptibility testing of Mycobacterium tuberculosis . This audit assessed the turnaround times of a district general hospital (DGH), assisted by the reference laboratory, for processing samples for Mycobacterium tuberculosis . A liquid culture system was in use . The hospital serves an area with a high prevalence of tuberculosis . Request forms and reference laboratory reports were examined for every new laboratory diagnosis of tuberculosis in 2000 . Time to result was taken as time from receipt of specimen in the laboratory to date of reporting by reference laboratory . Seventy-two new cases of tuberculosis were culture positive in 2000 . Median time to identification was 21.5 days and to antibiotic susceptibility results was 35 days . With liquid culture systems, acceptable turnaround times for processing mycobacteria are achievable, but in many DGHs this equipment is not available. Nihon Kokyuki Gakkai Zasshi, 2002 May, 40(5), 397 - 401 {A case of rapid exacerbation of a pulmonary infection with Mycobacterium intracellulare in an immunocompetent pregnant woman}; Kaneko T et al.; We report a very rare case in which pulmonary non-tuberculous mycobacteriosis with Mycobacterium intracellulare deteriorated acutely, presumably because of pregnancy . A 36-year-old immunocompetent woman was referred to our hospital with a cough and a slight fever of 3 weeks' duration when she was 5 months pregnant . Chest radiography at the first visit showed multiple large thin-walled cavities in the left middle and lower lung fields . After antibiotic, cough-depressant and theophyllin treatment, her symptoms almost disappeared for a while although Mycobacterium intracellulare was detected in her sputum . One month later, however, her symptoms were aggravated and infiltrative shadows were observed around the cavities on chest radiographs . She was treated with clarithromycin as well as the antituberculous drugs rifampicin and ethambutol until delivery, and then streptomycin was added . Owing to these medications, her symptoms and the presence of Mycobacterium intracellulare in the sputum were being gradually eliminated . Radiographic improvement of the infiltrative shadows and slight reduction of the size of the cavities were also observed . However, no further improvement of the radiographic findings was observed, despite continued treatment . Finally, it was concluded that this disease may not be curable by such medication . The patient eventually underwent a left pneumonectomy about one year after the first visit. J Cardiol, 2002 Jul, 40(1), 25 - 30 {Intractable infective endocarditis associated with supraaortic stenosis in Williams syndrome: a case report}; Maruyoshi H et al.; A 17-year-old man with supravalvular aortic stenosis associated with Williams syndrome was admitted to our hospital for intensive treatment for intractable infective endocarditis . The patient had a history of percutaneous balloon valvuloplasty for aortic stenosis in 1992 . He was well until late in 1999, when he had a high temperature after dental work-up . The diagnosis was infective endocarditis but antibiotic therapy was not effective . He was transferred to our clinic . Transthoracic echocardiography demonstrated bicuspid aortic valve, supraaortic stenosis, mitral valve prolapse with severe regurgitation and scattered vegetations on the anterior mitral and aortic valves . In addition, transesophageal echocardiography showed innumerable mobile vegetations located from Valsalva's sinus to the descending aorta . Aortic root and arch replacement with a homograft and mitral valve replacement with an artificial valve were successfully performed to eliminate the infective endocarditis . In the present patient, the flow jet across the supraaortic stenosis seemed to cause a predisposition to severe endocarditis. Mol Biochem Parasitol, 2002 Aug 7, 123(1), 1 - 10 Rapid positive selection of stable integrants following transfection of Plasmodium falciparum; Wang P et al.; With the near-completion of the genome sequence of Plasmodium falciparum, further understanding of this major human pathogen urgently requires more effective genetic tools . These must include faster and more reliable gene replacement or gene knockout techniques, essential for the analysis of gene function . We describe a serial system which uses the blasticidin S deaminase (bsd) gene of Aspergillus and the neomycin phosphotransferase II (neo) gene from transposon Tn5 as selectable markers for, respectively, transient transfection of malaria parasites and the selection of stable integrants . Challenge with blasticidin S (BS) enriches the parasite population transiently expressing the bsd gene, laying the foundation for the subsequent, much less frequent, integration event . Positive selection for this rare event is enormously facilitated by fusing the neo gene in frame to the replacement or knockout targeting gene . The sequence employed for the targeting (the polymorphic pppk-dhps gene of P . falciparum, as a model system) is truncated at the 5' end with no promoter located upstream, therefore neo cannot be expressed without specifically integrating within the genomic copy of the target gene . After BS selection, the culture is immediately exposed to geneticin (G418), leading to an apparently homogenous population of mutant parasites . As well as excluding spurious integrants at non-targeted sequences, this system greatly reduces the lengthy selection period for obtaining the desired mutants by eliminating the drug-on and drug-off cycles for the production of stable integrants, which are normally required by the single marker systems currently in use for transfection of malaria parasites . Curr Allergy Asthma Rep, 2002 Sep, 2(5), 368 - 78 A history of immune globulin therapy, from the Harvard crash program to monoclonal antibodies; Berger M; Processes for the large-scale fractionation of human plasma using cold ethanol were initially developed by Edwin Cohn and his colleagues at Harvard to provide albumin as a treatment for shock in World War II . Procedures for further purification of gamma globulins and other proteins precipitating at lower concentrations of ethanol were then developed by Oncley et al . Gamma globulin rapidly replaced convalescent and animal sera for the prevention and treatment of infectious diseases such as measles, hepatitis, and polio, then came into widespread use as replacement therapy in the primary immune deficiencies, which emerged in the antibiotic era of the early 1950s . Although it took 40 years to develop preparations of gamma globulin that could be safely given intravenously, the eventual accomplishment of that goal has led to better treatment of antibody deficiency syndromes and also the wide use of high-dose intravenous immunoglobulin in autoimmune and inflammatory diseases . Those uses continue to expand even as monoclonal antibodies are being introduced for specific infectious diseases in high-risk populations. Biochem J, 2002 Nov 15, 368(Pt 1), 131 - 6 Promoter-specific inhibition of transcription by daunorubicin in Saccharomyces cerevisiae; Marin S et al.; Several anti-tumour drugs exert some of their cytotoxic effects by direct binding to DNA, thus inhibiting the transcription of certain genes . We analysed the influence of the anti-tumour antibiotic daunorubicin on the transcription of different genes in vivo using the budding yeast Saccharomyces cerevisiae . Daunorubicin only affected wild-type yeast strains at very high concentrations; however, erg6 mutant strains (but not pdr1, pdr3 or pdr5 strains) were sensitive to daunorubicin at low micromolar concentrations . In Delta erg6 strains, daunorubicin inhibited the galactose-induced transcription by Gal4p in a specific manner, since the transcription of identical reporters driven by other activators (either constitutive or inducible) was not inhibited . The drug concentrations at which Gal4p function was inhibited did not affect cell growth or viability . Furthermore, daunorubicin inhibited the growth in galactose and the transcriptional induction of resident Gal4p-driven genes upon galactose addition, two processes absolutely dependent on Gal4p function . We propose that daunorubicin and some transcription factors compete for DNA sequences encompassing CpG steps, and that this is the main determinant of the effects of the drug on transcription in vivo . Our approach may foster the development of anti-tumour drugs with more specific mechanisms of action. J Drug Target, 2002 Jun, 10(4), 309 - 15 Improved brain delivery of benzylpenicillin with a peptide-vector-mediated strategy; Rousselle C et al.; Previous studies from our laboratory have demonstrated that the coupling of doxorubicin with SynB1 vector dramatically increases its brain uptake . In the present study, we have evaluated the broad application of this approach using another molecule: benzylpenicillin (B-Pc) . We, therefore, have coupled the beta-lactam antibiotic B-Pc with SynB1 and assessed its ability to cross the blood-brain barrier (BBB) using the in situ rat brain perfusion method . We first confirmed the very low brain uptake of free radiolabeled B-Pc . When B-Pc was coupled to SynB1, its uptake in brain was increased by a factor of 7, without compromising the BBB integrity . The vectorised B-Pc was distributed in all the gray areas assessed (frontal, parietal, and occipital cortex, thalamus, hippocampus, and striatum) . Moreover, using a wash-out procedure and a capillary depletion method, we have shown that the radiolabeled B-Pc was associated mainly with brain parenchyma . In summary, this study demonstrates the successful application of the use of SynB1 vector for the transport of B-Pc across the BBB. Crit Care Med, 2002 Aug, 30(8), 1778 - 81 Serum procalcitonin in cerebral ventriculitis; Berger C et al.; OBJECTIVES: The objective of this study was to test the hypothesis that serum proca