Antibiotics

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 procalcitonin is increased in patients with bacterial cerebral ventricular infections after the insertion of temporary external ventricular drains . PATIENTS AND METHODS: This open, prospective study included patients requiring temporary external ventricular drains for various neurologic conditions such as intracerebral hemorrhage with ventricular hemorrhage or space-occupying lesions in the posterior fossa (cerebellar infarctions or hemorrhages) . Patients experiencing primary central nervous system infection or sepsis were excluded . Procalcitonin, C-reactive protein, and white blood cell count were measured daily . Cerebrospinal fluid was investigated every other day, including cerebrospinal fluid cell count, lactate, glucose, and cerebrospinal fluid culture . Results were categorized according to presence of bacterial cerebrospinal fluid infection as determined by positive cerebrospinal fluid cultures . RESULTS: A total of 34 consecutive patients were included . Procalcitonin was significantly higher (4.7 vs . 0.2 ng/mL) in patients with proven bacterial ventriculitis . Cerebrospinal fluid cell count (456 vs . 478 cells/microL) could not distinguish bacterial infection from abacterial reactions, mainly because of blood contamination of the cerebrospinal fluid . CONCLUSION: Cerebrospinal fluid of patients treated with temporary external ventricular drains is frequently characterized by blood contamination because of the insertion procedure, the underlying neurologic disorder such as ventricular hemorrhage, or the presence of an abacterial chemical ventriculitis . Thus, diagnosis of a bacterial ventricular infection requiring immediate antibiotic therapy is less certain . Serum procalcitonin adds to the diagnostic precision in bacterial ventriculitis.

Rev Med Interne, 2002 Jul, 23(7), 638 - 41
{Actinomycosis of the appendix . Report of two cases}; Habib E et al.; INTRODUCTION: We report two patients with actinomycosis of the appendix extending to the caecum and the ileum, and diagnosed postoperatively on histological analysis, the authors reviewed the literature . EXEGESIS: Actinomycosis of the appendix can be acute or chronic . Diagnosis may be obtained preoperatively on the analysis of aspiration or biopsy material under CT scan control . It is frequently done postoperatively on the analysis of surgical specimen . Actinomycosis can be treated with antibiotics only during six months if the diagnosis is made preoperative, by surgery followed by antibiotics during 6-12 months, according to the extension of the actinomycosis, if the diagnosis is made after surgery, and by a combination of a surgery and antibiotics in complex forms . CONCLUSION: Actinomycosis of the appendix is an infrequent pathology that merits to be known . With antibiotic therapy, we can avoid surgery or wide resections.

Pediatr Neurol, 2002 Jul, 27(1), 62 - 4
Cavernous sinus thrombophlebitis in Nijmegen breakage syndrome; Hibner E et al.; The aim of the study was to present rarely reported neurologic complications in Nijmegen breakage syndrome . A 13-year-old female was referred because of chronic progressive headaches . There were dysmorphic features on physical examination, which suggested a diagnosis of chromosomal instability syndrome . The results of genetic and immunologic examinations confirmed the diagnosis . Cerebral magnetic resonance imaging revealed an 8 mm thickening of the meninges over the left hemisphere, corresponding with a chronic inflammatory condition, and symptoms of left cavernous thrombophlebitis were detected . Cerebrospinal fluid examination and an infusion test demonstrated disorders in its absorption . Antibiotic, anticoagulant and cerebral edema treatment was given and after 1 week improvement was observed . Regression of symptoms occurred after 14 days.

Acta Crystallogr C, 2002 Aug, 58(Pt 8), o447 - 9 Epub 2002 Jul 12.
Two (E,E)- and (Z,E)-thiazol-5-ylpenta-2,4-dienones; Breydo L et al.; In order to characterize the structural elements that might play a role in non-covalent DNA binding by the antitumor antibiotic leinamycin, we have solved the crystal structures of the two leinamycin analogs, methyl (R)-5-{2-{1-(tert-butoxycarbonylamino)ethyl}thiazol-4-yl}penta-(E,E)-2,4-dienoate, C(16)H(22)N(2)O(4)S, (II), and 2-methyl-8-oxa-16-thia-3,17-diazabicyclo{12.2.1}heptadeca-(Z,E)-1(17),10,12,14-tetraene-4,9-dione, C(14)H(16)N(2)O(3)S, (III) . The penta-2,4-dienone moiety in both of these analogs adopts a conformation close to planarity, with the thiazole ring twisted out of the plane by 12.9 (2) degrees in (II) and by 21.4 (4) degrees in (III).

Arch Intern Med, 2002 Aug 12-26, 162(15), 1715 - 20
Overuse of transthoracic echocardiography in the diagnosis of native valve endocarditis; Kuruppu JC et al.; BACKGROUND: Infective endocarditis (IE) is a diagnostic challenge due to its variable presentation and nonspecific clinical findings . The use of transthoracic echocardiography (TTE) has greatly improved the ability to diagnose IE early, and therefore reduce high mortality and morbidity rates . However, reliance on TTE to exclude IE may lead to overuse of this technology in patients with a low pretest probability of IE . METHODS: Prospective observational study of all patients referred for TTE to diagnose IE . Clinical factors were used to determine likelihood of IE based on the Von Reyn criteria, and the resulting diagnostic probabilities were correlated with abnormal TTE findings as well as duration of antibiotic therapy . RESULTS: One hundred eleven TTEs performed on 98 patients were included in the analysis . Over 70% of TTEs were obtained in patients in whom the diagnosis of IE was rejected by Von Reyn criteria . Therapeutic management (prolonged antibiotic administration) was associated significantly with Von Reyn categorization, and not significantly affected by TTE results . CONCLUSIONS: Most TTEs are obtained in patients with a low pretest probability of IE and do not contribute to therapeutic decision making . We propose a diagnostic algorithm to direct the use of TTE to patients with intermediate or high pretest probability of IE.

Laryngoscope, 2002 May, 112(5), 906 - 10
Nonsurgical management of parapharyngeal space infections: a prospective study; Sichel JY et al.; OBJECTIVE/HYPOTHESIS: Parapharyngeal infections, which can potentially cause life-threatening complications, may, in certain cases, be treated conservatively with no need for surgical drainage . A review of the literature reveals that the most recommended treatment of parapharyngeal infection is surgical drainage combined with intravenous antibiotic therapy . Several retrospective reports recommend conservative treatment with no surgical drainage . STUDY DESIGN: Prospective, nonrandomized . METHODS: A prospective study was performed on all patients with an infection limited to the parapharyngeal space . RESULTS: Twelve patients presented with clinical and radiological diagnosis of parapharyngeal infection during a 5-year period . Five patients showed obvious presence of pus in other spaces and therefore were excluded . Seven patients with no gross extension into other spaces and with no respiratory distress or septic shock were treated with intravenous amoxicillinclavulanic acid for 9 to 14 days (average period, 11 days) . All patients except one were children . All were cured with conservative management, and no surgical drainage was needed . None had any complications . CONCLUSION: Our results confirm the effectiveness of nonsurgical treatment of infections limited to the parapharyngeal space, at least in the pediatric population.

Pediatr Infect Dis J, 2002 May, 21(5), 439 - 41
Secondary syphilitic hepatitis in a fourteen-year-old male youth; Ozaki T et al.; An unusual case of a secondary syphilitic hepatitis in a 14-year-old male youth is presented . Although he had extremely high aspartate and alanine aminotransferase values, improvement was rapid after antibiotic therapy . Histologic examination of the liver performed during convalescence revealed patchy necrosis and inflammatory cell infiltration.

Laryngoscope, 2002 Mar, 112(3), 415 - 9
The evolution of surgery on the maxillary sinus for chronic rhinosinusitis; Lund V; OBJECTIVE: To examine the management of the maxillary sinus in chronic rhinosinusitis over the last 500 years . METHOD: A literature review was conducted . RESULT: The maxillary sinus was first recognized in the 16th century and its role as a source of infection became the focus of attention, beginning with Nathaniel Highmore in 1651 and continuing up until the 21st century . The surgical drainage of the sinus was achieved by a variety of routes, including the alveolar margin, anterior wall and middle and inferior meati . The rationale for these procedures, developed in a pre-antibiotic era, may be re-examined in the context of our present understanding of the pathophysiology of chronic rhinosinusitis . CONCLUSION: The maxillary sinus has been the focus of surgical attention from the 17th century onward largely as a result of its size and accessibility, initially reinforced by plain x-ray . However, in the 20th century, the advent of computed tomography and nasal endoscopy has reaffirmed the relationship of the maxillary sinus to the ostiomeatal complex in chronic rhinosinusitis, as originally demonstrated by pioneers such as Zuckerkandl, and redirected the focus of our therapeutic approaches.

Presse Med, 2002 Jun 15, 31(21 Pt 2), S15 - 8
{Update on the use of levofloxacin in the management of acute exacerbations of chronic bronchitis with risk factors}; Zuck P; INDICATIONS FOR ANTIBIOTICS: In patients with acute exacerbation of chronic bronchitis depend on the stage of the chronic disease . Theoretically, antibiotics are not necessary for acute exacerbation of simple chronic bronchitis, but may be needed to reinforce bronchodilatation therapy and respiratory physical therapy . If fever persists for more than three days, group 1 antibiotics can be prescribed . In a second stage (obstructive chronic bronchitis), antibiotic therapy can be useful for patients with two or three Anthonisen criteria: group 1 antibiotics for occasional exacerbation, group 2 antibiotics in case of failure or as first line treatment for patients with frequent exacerbations; anti-pneumococcal fluoroquinolones are a possible alternative . At a third stage (chronic respiratory failure), first line therapy should include group 2 antibiotics . THE BRONCHEA STUDY: Was designed to search for risk factors favoring frequent acute exacerbation of chronic bronchitis in adults . The findings suggest that certain classical risk factors such as age should be revisited . This study demonstrated the crucial need for rigorous surveillance by a lung specialist, the importance of not smoking, and the beneficial effect of optimized treatment . It was also found that earlier initiation of group 2 antibiotic therapy may be useful for patients with a high risk of exacerbation.

Vet Clin North Am Small Anim Pract, 2002 Jul, 32(4), 839 - 49
Feline nasopharyngeal polyps; Muilenburg RK et al.; In summary, an ideal diagnostic plan for cats with suspected FNPs should include a thorough anesthetized oropharyngeal examination, otoscopic examination, and imaging studies, which may consist of a bulla radiographic series or specialized imaging studies such as CT or MR scans . In general, if signs indicative of otitis media are present, ventral bulla osteotomy should be advised . As a result of the distinct appearance of FNPs, a preoperative biopsy is not indicated in all instances but should be considered if there are atypical features to the history or presentation . Traction-avulsion of polyps through the external ear canal or auditory tube from the oropharynx may have a lower success rate than traction-avulsion combined with ventral bulla osteotomy . If the veterinarian opts to treat FNPs by traction-avulsion alone as a result of financial constraints imposed by the client, the client should be strongly cautioned regarding potential recurrence . Postoperative complications are possible with any treatment option, but neurologic impairment, including Horner's syndrome, facial neuropathy, and hypoglossal neuropathy, is significantly more likely after surgical intervention by ventral bulla osteotomy than after traction-avulsion alone . A high percentage of these complications are self-limiting . In all instances, appropriate culture and sensitivity and biopsy specimens should be collected so as to enable provision of appropriate postoperative care . Antibiotic therapy should be provided based on culture and sensitivity test results . The use of postoperative steroids to prevent recurrence is controversial.

J Health Econ, 2002 Jul, 21(4), 709 - 18
On the implications of endogenous resistance to medications; Laxminarayan R et al.; Uniform treatment guidelines are often used in medicine to ensure that all physicians prescribe a safe, efficacious, and cost-effective drug in treating a medical condition . The main message of this paper is that a policy of uniform treatment based on the standard cost-effectiveness criterion may be inappropriate when drug resistance is endogenous, and selection pressure imposed by the use of any single drug (antibiotic, antiviral, or antimalarial) leads sooner or later to the evolution of resistance (by bacteria, viruses, or parasites) to that drug . The paper shows that a mixed treatment policy of multiple drug use is generally desirable, and characterizes analytically the conditions under which it is optimal.

Eur J Intern Med, 2002 Aug, 13(5), 324 - 328
Modern management of non-chemotherapy drug-induced agranulocytosis: a monocentric cohort study of 90 cases and review of the literature; Andres E et al.; BACKGROUND: The present study reports a monocentric experience of 90 drug-induced agranulocytosis cases and discusses their management, in particular the role of hematopoietic growth factors . METHODS: Data from 90 patients with drug-induced agranulocytosis who met the criteria of the IAAAS group and of Benichou and Solal-Celigny {Nouv Rev Fr Hematol 1993; 33: 257.} were retrospectively reviewed . All cases were extracted from a cohort study of the Hopitaux Universitaires de Strasbourg, France . Data were specifically analyzed with regard to the use of hematopoietic growth factors (in 42 patients) . RESULTS: Mean patient age was 63 (range 17-95) years and the sex ratio (M/F) was 0.39 . An underlying disease was present in 37% of the patients . Antibiotics (25%), antithyroid drugs (23%), and antiaggregative platelet agents (16%) were the most frequent causative drugs . Main clinical features included isolated fever (41%), septicemia or septic shock (31%), and pneumonia (10%) . Mean neutrophil count was 0.13 (range 0-0.46)x10(9)/l . Outcome was favorable in 98% of patients . The mean durations of hematological recovery (neutrophil count over 1.5x10(9)/l), antibiotic therapy, and hospitalization was 8.5 (range 2-21) days, 9.2 (range 2-21) days, and 10.5 (range 3-23) days, respectively . All patients were treated with broad-spectrum antibiotics and 42 patients with hematopoietic growth factors . In these 42 patients, the mean durations for hematological recovery, antibiotic therapy, and hospitalization were significantly reduced at: 6.3 (range 2-16) days, 7.1 (range 2-16) days, and 9.1 (range 3-23) days, respectively (all P<0.05) . CONCLUSIONS: The present study shows that new causative drugs are emerging (antibiotics, antithyroid, and antiaggregative platelet agents), that drug-induced agranulocytosis remains typically a serious accident with severe sepsis, and that modern management with broad spectrum antibiotics and hematopoietic growth factors may reduce the mortality.

Cardiol Rev, 2002 Jul-Aug, 10(4), 199 - 210
Role of infection in atherosclerosis and coronary artery disease: a new therapeutic target?
Frishman WH, Ismail AA.
There is growing evidence that inflammatory processes may be involved in the development of atherosclerosis and its complications . Viral and bacterial pathogens have been implicated as possible causative factors in the pathogenesis of coronary artery disease and postangioplasty restenosis . Antibiotic trials have been completed examining which treatment of infection can prevent the complications of coronary artery disease . In high-risk patients, the results of these most recent studies have not revealed any benefit of treatment.

South Med J, 2002 Jul, 95(7), 751 - 2
Tuberculous empyema necessitatis in a man infected with the human immunodeficiency virus; Jover F et al.; Empyema necessitatis is a collection of inflammatory tissue that ruptures spontaneously through a weakness in the chest wail into surrounding soft tissues . Although empyema necessitatis can be caused by a number of infectious agents, mycobacteria are the most frequently implicated . Empyema was a much more common complication of pulmonary tuberculosis in the preantibiotic era than it is today . We describe a 22-year-old man with human immunodeficiency virus (HIV) infection who had tuberculous empyema necessitatis and was successfully treated with surgical debridement and antibiotic therapy.

Neonatal Netw, 2001 Jun, 20(4), 23 - 30
Congenital toxoplasmosis; Martin S; Toxoplasma gondii, a parasite, has three modes of transmission: oral intake of raw or undercooked meat or contaminated fruits and vegetables, ingestion of materials contaminated with cat feces, and transplacental infection . The focus of this article is congenital toxoplasmosis, which is transmitted to the fetus across the placenta . When primary infection of the mother occurs during pregnancy, there is a 40 percent chance of fetal infection; rate of transmission and severity of infection are related to gestational age at the time of infection . The brain and retina are often affected, and there can be a wide range of clinical disease . Amniocentesis or cordocentesis provides the most accurate diagnosis . At birth, 80-90 percent of infants with congenital toxoplasmosis are asymptomatic . But further testing may reveal retinal and central nervous system abnormalities, and there is a risk of long-term sequelae . Chorioretinitis, hydrocephalus, intracranial calcifications, and convulsions are the typical presentation of classic congenital toxoplasmosis . Serology is the most common method of diagnosing neonatal infection, but more complex tests are also utilized . The prognosis for the untreated infant is poor; however, when antibiotic therapy is started early, the rate of sequelae is reduced significantly.

Hepatogastroenterology, 2002 Jul-Aug, 49(46), 1141 - 3
Case of a bleeding pseudoaneurysm of the middle colic artery complicating acute pancreatitis; Toyonaga T et al.; Massive bleeding from a pseudoaneurysm is rare, but it can be a life-threatening complication in patients with acute pancreatitis . We present a case in which massive bleeding from a pseudoneurysm in the middle colic artery complicating acute pancreatitis was successfully treated by transcatheter embolization and by continuous regional arterial infusion of a protease inhibitor and antibiotic . We also discuss the clinical features, diagnosis and treatment of such lesions in light of the literature . We emphasize the value of computed tomography in the early diagnosis of mesenteric hematoma in cases of acute pancreatitis and the value of angiography for control of bleeding from the complicating pseudoaneurysm.

Oncogene, 2002 Aug 1, 21(33), 5188 - 92
Deficiency in BRCA2 leads to increase in non-conservative homologous recombination; Larminat F et al.; The BRCA2 tumor suppressor has been implicated in the maintenance of genomic integrity through a function in cellular responses to DNA damage . The BRCA2 protein directly associates with Rad51, that is essential for repair of double-strand breaks (DSBs) by homologous recombination (HR) . In this report, we study the BRCA2-defective Chinese hamster cell mutant V-C8 for its ability to perform homology-directed repair (HDR) between repeated sequences . V-C8 cells were recently shown to be defective in Rad51 foci formation in response to DNA damage . Strikingly, we find that these BRCA2 mutant cells exhibit a strong stimulation of HDR activity compared to the V79 parental cells, which harbor a wild-type BRCA2 . Furthermore, molecular characterization of the HDR products shows that loss of BRCA2 in V-C8 cells leads to significant reduction in Rad51-dependent gene conversion but strong enhancement of Rad51-independent single-strand annealing (SSA) events frequency . These data imply that, when HDR by conservative gene conversion is impaired, DSBs usually repaired by this pathway are instead resolved by other non-conservative HDR subpathways . Therefore, high chromosomal instability in BRCA2-deficient cells presumably results from enhancement of error-prone repair mechanisms, such as SSA.

Mol Microbiol, 2002 Aug, 45(3), 735 - 44
Regulation of tylosin production and morphological differentiation in Streptomyces fradiae by TylP, a deduced gamma-butyrolactone receptor; Stratigopoulos G et al.; During promoter-probe analysis carried out in Streptomyces lividans, the TylP protein powerfully inhibited reporter gene expression from the tylP promoter, raising the likelihood that tylP is autoregulated in its native host, Streptomyces fradiae . Also in S . lividans, TylP negatively controlled the tylQ promoter, even though tylQ could still be switched off in S . fradiae strains specifically disrupted in tylP . Under the latter conditions, tylosin production was brought forward and enhanced, whereas overexpression of tylP resulted in reduced levels of the antibiotic, accompanied by barely detectable transcription from multiple genes of the tylosin biosynthetic cluster . Unexpectedly, overexpression of tylP reduced transcription of tylS, a transcriptional activator essential for tylosin production . This was probably a direct effect, as TylP also reduced expression from the tylS promoter in S . lividans . For these several reasons, we conclude that TylP acts as a repressor during tylosin biosynthesis . In addition, TylP influences morphological differentiation in S . fradiae . On solid media, strains in which tylP was disrupted sporulated significantly earlier than wild type and, in liquid culture, displayed hyperfragmentation.

J Chromatogr B Analyt Technol Biomed Life Sci, 2002 Sep 5, 776(2), 177 - 82
High-performance liquid chromatographic assay validation of Manumycin A in mouse plasma; Gonzales J et al.; Manumycin A is a natural antibiotic produced by Streptomyces parvulus that has antineoplastic activity against a variety of human cancers in nude mouse models . We have developed a highly sensitive reverse phase high-performance liquid chromatography (HPLC) method based on ultraviolet (UV) detection for the determination of manumycin A in mouse plasma . Manumycin A was isolated from mouse plasma by solid-phase extraction . A gradient elution of methanol and 0.05 M H(3)PO(4) with 0.2% triethylamine mobile phase was employed and separation was achieved with a C(18) analytical column . Manumycin A was detected by UV absorption at 345 nm . Retention time for manumycin A was 8.9+/-0.2 min . The manumycin A peak was baseline resolved, with the nearest peak at 1.5 min distance and no interfering peaks detected . Inter- and intra-day coefficients of variance were less than 6.1 and 5.1%, respectively . Based on an extracted manumycin A standard plasma sample of 0.25 microg/ml, the assay precision was 99.8% with a mean accuracy of 95.1% . At plasma concentrations of 0.5 and 5 microg/ml, the mean recovery rates of manumycin A were 59.64 and 60.28%, respectively . The lower limit of detection (LLD) for manumycin A was 0.1 microg/ml in mouse plasma . The lower limit of quantification (LLQ) for manumycin A was 0.125 microg/ml . Results of the stability study indicated that when frozen at -80 degrees C, manumycin A was stable in mouse plasma for up to 2 weeks . This method is useful in quantification of manumycin A in mouse plasma for clinical pharmacology studies in mice .

Acta Biochim Pol, 2002, 49(1), 145 - 55
A comparison of the in vitro genotoxicity of anticancer drugs idarubicin and mitoxantrone; Blasiak J et al.; Idarubicin is an anthracycline antibiotic used in cancer therapy . Mitoxantrone is an anthracycline analog with presumed better antineoplastic activity and lesser toxicity . Using the alkaline comet assaywe showed that the drugs at 0.01-10 microM induced DNA damage in normal human lymphocytes . The effect induced by idarubicin was more pronounced than by mitoxantrone (P < 0.001) . The cells treated with mitoxantrone at 1 microM were able to repair damage to their DNA within a 30-min incubation, whereas the lymphocytes exposed to idarubicin needed 180 min . Since anthracyclines are known to produce free radicals, we checked whether reactive oxygen species might be involved in the observed DNA damage . Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by idarubicin, but did not affect the extent evoked by mitoxantrone . Lymphocytes exposed to the drugs and treated with endonuclease III or formamidopyrimidine-DNA glycosylase (Fpg), enzymes recognizing and nicking oxidized bases, displayed a higher level of DNA damage than the untreated ones . 3-Methyladenine-DNA glycosylase II (AlkA), an enzyme recognizing and nicking mainly methylated bases in DNA, increased the extent of DNA damage caused by idarubicin, but not that induced by mitoxantrone . Our results indicate that the induction of secondary malignancies should be taken into account as side effects of the two drugs . Direct strand breaks, oxidation and methylation of the DNA bases can underlie the DNA-damaging effect of idarubicin, whereas mitoxantrone can induce strand breaks and modification of the bases, including oxidation . The observed in normal lymphocytes much lesser genotoxicity of mitoxantrone compared to idarubicin should be taken into account in planning chemotherapeutic strategies.

Toxicology, 2002 Aug 15, 177(2-3), 123 - 30
Neocarzinostatin induces Mre11 phosphorylation and focus formation through an ATM- and NBS1-dependent mechanism; Yuan SS et al.; DNA double-strand breaks, if unrepaired, may lead to the accumulation of chromosomal aberrations and eventually cancer cell formation . Components of the Rad50/NBS/Mre11 nuclease complex are essential for the effective repair of DNA double-stranded breaks . Here, we show that neocarzinostatin, a radiomimetic enediyne antibiotic, induces phosphorylation and nuclear focus formation of Mre11 and NBS1 through a cell cycle-independent mechanism . Furthermore, neocarzinostatin-induced Mre11 phosphorylation and nuclear focus formation are defective in AT and NBS cells, but not wild type cells . Our results suggest that ATM and NBS1 are required for the effective repair of neocarzinostatin-induced DNA double-strand breaks by both non-homologous end joining and homologous recombinational repair pathways.

Am J Gastroenterol, 2002 Jul, 97(7), 1687 - 95
Genotyping of Helicobacter pylori in paraffin-embedded gastric biopsy specimens: relation to histological parameters and effects on therapy; Scholte GH et al.; OBJECTIVES: Colonization with Helicobacterpylori can lead to GI disease . Bacterial genotypes and host factors, such as acid production, can influence the progress of disease . We investigated H . pylori genotypes and histological parameters in the same paraffin-embedded gastric biopsy specimens . METHODS: Paraffin-embedded antrum and corpus biopsy samples from 75 gastroesophageal reflux disease patients were histologically examined and tested for H . pylori vacA (s and m regions), cagA, and iceA genotypes . Patients were investigated at baseline (58 H . pylori positive and 17 H . pylori negative) and after treatment with omeprazole with or without additional antibiotic therapy . RESULTS: Genotyping at baseline was complete in 52 (90%) of the 58 H . pylori positive patients . Multiple genotypes were detected in eight (14%) of these . Genotypes were highly consistent between antrum and corpus biopsy specimens at baseline and in follow-up samples . Genotypes from paraffin sections matched those from corresponding cultured strains in 10 selected cases . In the antrum, the degree of inflammation was associated with vacA s1 and cagA+ genotypes, and the degree of neutrophil activity was associated with the cagA+ genotype . In the corpus, the degree of inflammation was significantly associated with vacA s1, cagA+, and iceA1 genotypes and the degree of atrophy was associated with vacA s1, m1, and cagA+ genotypes, whereas the degree of neutrophil activity was associated with vacA s1 and cagA+ genotypes . vacA s2 and cagA-strains appeared more resistant to antibiotic therapy, irrespective of resistance to clarithromycin . CONCLUSIONS: Our findings confirm the relevance of the H . pylori genotypes for the severity of gastric disease and the efficacy of antibiotic therapy.

J South Orthop Assoc, 1999 Fall, 8(3), 193 - 202
Open fractures of the hand; Gonzalez MH et al.; Open fractures of the hand are a challenging clinical problem for the orthopedic surgeon . The fracture is often comminuted with substance loss . Additionally, the fracture site can be contaminated by foreign material . The soft tissue envelope is violated with a variable degree of tissue devitalized . The wound contamination and tissue destruction lead to a rate of infection that can be much higher than that for a closed fracture . Initially, management of a significant soft tissue injury must take precedence over definitive fracture fixation . Proper staging of debridement, wound closure, and definitive fixation is paramount in minimizing infection while obtaining fracture union.

Vnitr Lek, 2002 Jun, 48(6), 578 - 82
{Rifaximin in the treatment of hepatic encephalopathy}; Lata J et al.; Hepatic encephalopathy is a frequent and serious complication of liver cirrhosis . Usually it is treated by non-absorbable disaccharides or antibiotics and its treatment is often difficult and associated with undesirable effects . The objective of our investigation was to evaluate the safety and effectiveness of a new antibiotic used in this indication--rifaximine . With rifaximine, 400 mg three times per day, a total of 25 patients were treated for a 10-day period . Significant improvement of the manifestations of encephalopathy occurred (evaluated by the grade of encephalopathy, test of combining numerals, the degree of flapping tremor and the arterial ammonia level) . None of the patients developed undesirable effects . Rifaximine seems an effective, safe drug for hepatic encephalopathy.

Vnitr Lek, 2002 Jun, 48(6), 542 - 8
{Basic questions in therapy of the diabetic foot}; Jirkovska A; The diabetic foot syndrome including foot tissue impairment distally from the ankle associated with neuropathy and angiopathy in diabetic patients is the main cause of amputations . However, amputations are not inevitable and the provision of rapid and intensive treatment of foot complications in multidisciplinary foot clinics can reduce the number of amputations in diabetic patients . The fundamental principle in the therapy is comprehensive approach; the omitting of any of the principle of the therapy may contribute to its failure . The most frequent case in the praxis is the omitting of the of-loading of the ulcers e.g . by the therapeutic shoes (half-shoes) or special contact cast . The infection control by local debridement and systemic antibiotic therapy is crucial . The higher risk of infection may be related to abnormalities in immunity . The condition for wound healing is good vascular supply by percutaneous transluminal angioplasty and/or by peripheral vascular bypasses most frequent performed on infrapopliteal vessels . Especial attention is necessary to give to therapy of Charcot osteoarthropathy . Good metabolic control in some patients is achievable only by intensive insulin treatment, sometimes by insulin pumps . Early recognition of the at-risk patients and the prompt institution of preventive measures may stop new ulcerations and amputations.

Eur J Emerg Med, 2002 Jun, 9(2), 167 - 9
Adult acute epiglottitis and foreign body in the throat - chicken or egg?
Chung CH.
A 53 year old man presented with the chief complaint of having a fish bone stuck in the throat for about 1 h . There was no dysphagia or respiratory symptoms . Plain lateral neck X-ray, direct laryngoscopy and oesophagogastroduodenoscopy showed a grossly swollen epiglottis with narrowing of the laryngeal lumen . No foreign body was found . His condition improved rapidly with intravenous antibiotic therapy . As acute epiglottitis may be a sudden life-threatening condition, a high index of suspicion should be maintained for patients who present with alleged foreign bodies in the throat.

Bioorg Med Chem Lett, 2002 Aug 19, 12(16), 2163 - 5
Synthesis and biological evaluation of 9-substituted tetracycline derivatives; Koza DJ et al.; The synthesis of 9-substituted tetracycline derivatives has been accomplished by the reaction of C9 diazonium tetrafluoroborate tetracycline salts with organotin reagents under modified Stille coupling conditions . Several of these unreported derivatives show promising in vitro biological activity against tetracycline resistant and antibiotic resistant bacteria.

Mil Med, 2002 Jul, 167(7), 546 - 51
The cause of death in smallpox: an examination of the pathology record; Martin DB; OBJECTIVE: Because the cause of death in smallpox remains controversial, the human pathology record was examined . METHODS: The surviving case series of smallpox pathology in humans as well as other review articles from English language journals written during the last 200 years were reviewed . RESULTS: The skin lesions in smallpox developed as a result of viral damage and inflammation . Secondary bacterial infection did not occur until the scabs started shedding . During the papular stage of skin eruption, a secondary viremia caused focal lesions in the pharynx, larynx, tongue, trachea, and esophagus in descending frequency . The virus also caused potentially lethal interstitial pneumonitis as well as tubulointerstitial nephritis . CONCLUSIONS: The cytopathic effects of smallpox cause death . The data did not support previously promulgated theories attributing death to a bacterial sepsis syndrome seeded from the pustules or immune complex deposition . In a future outbreak, antibiotic therapy would minimally influence mortality.

Biopolymers, 2002 Sep, 64(6), 328 - 36
Self-aggregation properties of spin-labeled zervamicin IIA as studied by PELDOR spectroscopy; Milov AD et al.; In this article, the pulsed double electron-electron resonance in electron spin-echo (PELDOR) technique is applied to study the self-aggregation of spin-labeled zervamicin IIA, a hexadecapeptide antibiotic of fungal origin, which is known to form ion channels in a phospholipid double layer . Measurements of the ion channel forming properties and the antibiotic activity of the analog indicate that replacement of the C-terminal phenylalaninol by the amino-2,2,6,6-tetramethylpiperidinyloxy (TEMPO) residue does not influence the biophysical and biological properties . The dipole-dipole interaction between the spin labels of the fully biologically active peptide analog was studied in frozen (77 K) glassy solutions in different ratios of toluene-methanol . The spin-labeled zervamicin IIA molecules were shown to form aggregates . An average distance between the spin labels in the aggregates was estimated to be in the range of 25-35 A (depending on the solvent composition), indicating that the amphiphilic helical peptide molecules are oriented in an antiparallel fashion . Increasing of methanol content in the solution results in a loosening of the aggregate structure . It was shown that the fraction of aggregated zervamicin IIA molecules is less than 44-67% depending on the solvent composition . The general usefulness of the method to obtain structural long-range information in a range of several tens of angstroms is demonstrated by comparison with the peptide cluster of trichogin GA IV .

Cancer, 2002 Jul 15, 95(2), 322 - 30
Phase II study of induction chemotherapy with paclitaxel, ifosfamide, and carboplatin (TIC) for patients with locally advanced squamous cell carcinoma of the head and neck; Shin DM et al.; BACKGROUND: This Phase II trial was conducted to determine the response rate, particularly of the primary sites, tolerability, and toxicity of induction chemotherapy of paclitaxel, ifosfamide, and carboplatin for patients with previously untreated locally advanced squamous cell carcinoma of the head and neck (SCCHN) . We also hypothesized that improved complete response (CR) rates with the induction chemotherapy may render better survival rates with subsequently delivered definitive local treatment . METHODS: All eligible patients with locally advanced SCCHN received two courses of induction chemotherapy and underwent repeated head and neck examination and computed tomography or magnetic resonance imaging scans . If the patients achieved responses (CR or partial {PR}), they received two more courses of chemotherapy before undergoing definitive local treatment . Induction chemotherapy consisted of paclitaxel (T; 175 mg/m(2) in a 3-hour infusion) on Day 1, ifosfamide (I; 1000 mg/m(2) in a 2-hour infusion) on Days 1-3 with intravenous mesna (200 mg/m(2) before and 400 mg/m(2) after ifosfamide), and carboplatin (C) using the Calvert formula for the area under the plasma concentration-versus-time curve of 6 on Day 1, repeated every 3-4 weeks . Prophylactic hematopoietic growth factors or antibiotics were not used in this study . Definitive local treatment was given based on the investigators' preference . RESULTS: Fifty-four patients were registered and 52 patients were assessable for response to induction chemotherapy; 2 were not evaluable . After four courses of induction chemotherapy, the CR rates of the primary and lymph node sites were 60%, and 41%, respectively . For both primary and lymph node sites, there were 31% CRs and 50% PRs with an overall response rate of 81% . Five (9%) patients developed neutropenic fever, all of whom recovered with antibiotic therapy . Two (4%) patients had infection without neutropenia and recovered without any complication . Grade 3/4 thrombocytopenia and anemia occurred in three (6%) and four (7%) patients, respectively . Grade 3/4 fatigue developed in four (7%), arthralgia/myalgia in two (4%), peripheral neuropathy in two (4%), and orthostatic hypotension in two (4%) patients . One patient died of severe anaphylaxis although a maximized resuscitation effort was made . With a median follow-up of 22 months, the organ preservation rate was about 81% (42 of 52 patients) . Although survival rates were not primary end points in this study, with a median follow-up of 22 months, 43 (83%) patients are still alive . Overall 1 and 2-year survival rates were 88% and 82%, respectively . Disease-free 1 and 2-year survival rates were 88% and 77% respectively . CONCLUSIONS: TIC induction chemotherapy is associated with a high CR rate at the primary sites and with excellent survival and organ preservations rates with subsequently delivered definitive local therapy . The regimen was also well tolerated in the majority of patients . The TIC regimen should be developed further in the context of induction chemotherapy followed by concomitant chemoradiotherapy or with specific molecular targeted agents .

Semin Pediatr Infect Dis, 2002 Apr, 13(2), 72 - 8
The impact of influenza in children; Munoz FM; The highest infection rates with influenza virus occur in young children because of their lack of prior immunity and prior exposure to the virus . Most children with influenza virus infection are healthy otherwise . Previously healthy children who have influenza in their first year of life have a substantial risk for developing serious disease . An underlying chronic medical condition further increases this risk . Infants, young children, and children with underlying conditions have the highest rates of outpatient medical visits and hospitalizations for acute respiratory disease during influenza epidemics . Secondary bacterial infections, antibiotic use, and other complications of influenza are consequences of influenza virus infection in children of all ages . Annual immunization with influenza vaccine is recommended for any child older than 6 months of age in whom prevention of disease is desirable, and particularly in those with underlying medical conditions . The consequences of infection in infants younger than 6 months of age can be modified by maternal immunization currently recommended for women in the second or third trimester of pregnancy during the influenza season . Family members, including siblings, and all other close contacts should receive influenza vaccine to reduce the possibility of transmission to children at risk . Immunization of all children has a positive impact on the occurrence of influenza infection and its complications, both in those at greater risk and in the entire population.

Khirurgiia (Sofiia), 2001, 57(5-6), 29 - 31
{Contusion traumas with damaged entity of the eye globe}; Vangelova A; PURPOSE: Examination of the etiology, the clinical history of the injury, the functional and anatomic result after contusion traumas with damaged entity of the eye globe . MATERIAL AND METHODS: Retrospective examination of the clinical documentation of 35 patients /35 eyes/, treated in Emergency Medical Center during the period 1994-1996 . RESULTS AND DISCUSSION: The etiology shows that traumas resulting from housework prevail . According to their localization the ruptures are: scleral--19 eyes (54.28%), corneo-scleral--13 eyes (37.14%) and corneal--3 eyes (8.57%) . Prolaps of uvea and vitreous was diagnosed with all the eyes . It was massive in the scleral and corneo-scleral ruptures . No eye underwent primary enucleation . The therapeutical behavior consists in primary reconstructive operation, general and local antibiotic, cortico-steroidal and non-steroidal anti-flammatory therapy . The functional and anatomic results are bad: absence of visual acuity with 51.42% of the eyes and vision up to 20/200 with 45.71%, subatrophy of the eye globe during the first 6 months after the trauma with 18 eyes (51.42%) . CONCLUSION: The contusion traumas with damaged entity of the eye globe are hard traumatic injuries which usually end with bad functional, anatomic and cosmetic results . The consequence is constant invalidation of the patients.

Z Gastroenterol, 2002 Jul, 40(7), 511 - 6
{Gastric outlet obstruction in chronic granulomatous disease}; Born M et al.; We report the case of a three year old dystrophic boy who suffered from vomiting, loss of weight and fever . In the history there were several episodes of severe infections which had repeatedly lead to hospitalisation . The cause of the actual disorder was a gastric manifestation of chronic granulomatous disease, which led by an inflammatory thickening of the gastric wall to a gastric outlet obstruction . Treatment with prednisone and gamma interferon normalised the thickness of the gastric wall and gastric outlet function . A prophylactic treatment with antibiotic and antifungeal agents was started . During the following 13 months no further severe infections were observed . We discuss incidence, kinds of manifestation, diagnostics and therapeutical options of the disease and give an overview of the literature.

Eur Biophys J, 2002 Jul, 31(4), 294 - 305 Epub 2002 Apr 13.
Ion passage pathways and thermodynamics of the amphotericin B membrane channel; Resat H et al.; Amphotericin B is a polyene macrolide antibiotic used to treat systemic fungal infections . Amphotericin B's chemotherapeutic action requires the formation of transmembrane channels, which are known to transmit monovalent ions . We have investigated the ion passage pathways through the pore of a realistic model structure of the channel and computed the associated thermodynamic properties . Our calculations combined the free energy computations using the Poisson equation with a continuum solvent model and the molecular simulations in which solvent molecules were present explicitly . It was found that there are no substantial structural barriers to a single sodium or chloride ion passage . Thermodynamic free energy calculations showed that the path along which the ions prefer to move is off center from the channel's central axis . In accordance with experiments, Monte Carlo molecular simulations established that sodium ions can pass through the pore . When it encounters a chloride anion in the channel, the sodium cation prefers to form a solvent-bridged pair configuration with the anion.

J Inorg Biochem, 2002 Jul 25, 91(1), 339 - 48
Supramolecular structures of metronidazole and its copper(II), cobalt(II) and zinc(II) coordination compounds; Galvan-Tejada N et al.; In this work we present the synthesis and structural and spectroscopic characterization of Cu(II), Co(II) and Zn(II) coordination compounds with the antibiotic metronidazole ({double bond}emni) . Coordination to metal ions is through its imidazolic nitrogen, while the hydroxyethyl and nitro groups act as supramolecular synthons . {Co(emni)(2)Br(2)}, and {Zn(emni)(2)X(2)} (X(-)=Cl, Br) stabilize zig-zag chains, and a 2D supramolecular structure is formed by inter-chain contacts through inter-molecular hydrogen-bonding . Pleated sheet or layers are formed by {Co(emni)(2)Cl(2)} and {Cu(emni)(2)Cl(H(2)O)}(2)Cl(2), respectively . The dinuclear Cu(II) compound {Cu(emni)mu(O(2)CMe)(2)}(2) gives a one-dimensional zig-zag arrangement . The contribution of metal ions in metronidazole coordination compounds is shown in the stabilization of the different aggregate structures.

J Am Geriatr Soc, 2002 Jul, 50(7 Suppl), S236 - 41
Resistant pathogens in respiratory tract infections in older people; Bonomo RA; Bronchitis, bronchiectasis, and pneumonia are the most common respiratory tract infections observed in older people and are the leading causes of morbidity and mortality associated with infection . Accurate diagnosis of respiratory tract infections in older people is problematic because of the lack of clear symptoms and signs that are usually seen in younger patients . In addition, the increasing prevalence of bacterial resistance to antibiotic therapy highlights the importance of appropriate therapy . The following review examines the issues associated with the accurate diagnosis of respiratory tract infections, optimal therapy for older patients, and the mechanisms of emerging bacterial resistance to antibiotic therapy.

Dermatol Clin, 2002 Apr, 20(2), 283 - 9
Cutaneous manifestations of Epstein-Barr virus infection; Ikediobi NI et al.; The most common cutaneous manifestations of EBV include IM, OHL, and cutaneous lymphoproliferative disorders . Infectious mononucleosis is a self-limited manifestation of acute EBV infection . The transient rash that occurs quite commonly in patients with IM who have received antibiotic therapy is an erythematous, maculopapular eruption, usually located on the trunk and upper extremities . Oral hairy leukoplakia occurs in immunosuppressed HIV-positive and HIV-negative individuals . In HIV-positive individuals, it serves as an indicator of disease severity and rapid progression to AIDS . The presence of OHL in an individual should prompt the clinician to perform a through history-taking and investigation of immune status . Cutaneous lymphoproliferative disorders associated with EBV occur in individuals with congenital or acquired immunodeficiency syndromes.

Chem Commun (Camb), 2002 Mar 21, (6), 556 - 7
Electrospray ionisation mass spectrometric detection of weak non-covalent interactions in nogalamycin-DNA complexes; Colgrave ML et al.; We demonstrate the use of electrospray ionisation mass spectrometry (ESI-MS) in high salt solutions for the analysis of weak non-covalent complexes of the anthracycline antibiotic nogalamycin with novel DNA hairpin structures; high signal-to-noise ratios for the complexes in the absence of bound Na+ ions permits relative binding affinities to be estimated.

Chem Commun (Camb), 2002 Apr 7, (7), 742 - 3
Total synthesis of fostriecin (CI-920) via a convergent route; Miyashita K et al.; Fostriecin, a potent and promising antitumor antibiotic, was stereoselectively synthesized via a convergent route involving a three-segement coupling procedure.

Biochemistry, 2002 Jul 23, 41(29), 9184 - 96
Timing of epimerization and condensation reactions in nonribosomal peptide assembly lines: kinetic analysis of phenylalanine activating elongation modules of tyrocidine synthetase B; Luo L et al.; The cyclic decapeptide antibiotic tyrocidine has D-Phe residues at positions 1 and 4, produced during peptide chain growth from L-Phe residues by 50 kDa epimerase (E) domains embedded, respectively, in the initiation module (TycA) and the TycB3 module of the three-subunit (TycABC), 10-module nonribosomal peptide synthetase . While the initiation module clearly epimerizes the aminoacyl thioester Phe1-S-TycA intermediate, the timing of epimerization versus peptide bond condensation at internal E domains has been less well characterized in nonribosomal peptide synthetases . In this study, we use rapid quench techniques to evaluate a three-domain (ATE) and a four-domain version (CATE) of the TycB3 module and a six-domain fragment (ATCATE) of the TycB2(-3) bimodule to measure the ability of the E domain in the TycB3 module to epimerize the aminoacyl thioester Phe-S-TycB3 and the dipeptidyl-S-enzyme (L-Phe-L-Phe-S-TycB3 if L-Phe-D-Phe-S-TycB3) . The chiralities of the Phe-S-enzyme and Phe-Phe-S-enzyme species over time were determined by hydrolysis and chiral TLC separations, allowing for the clear conclusion that epimerization in the internal TycB3 module occurs preferentially on the peptidyl-S-enzyme rather than the aminoacyl-S-enzyme, by a factor of about 3000/1 . In turn, this imposes constraints on the chiral selectivity of the condensation (C) domains immediately upstream and downstream of E domains . The stereoselectivity of the upstream C domain was shown to be L-selective at both donor and acceptor sites ((L)C(L)) by site-directed mutagenesis studies of an E domain active site residue and using the small-molecule surrogate D-Phe-Pro-L-Phe-N-acetylcysteamine thioester (D-Phe-Pro-L-Phe-SNAC) and D-Phe-Pro-D-Phe-SNAC as donor probes.

Microb Drug Resist, 2002 Summer, 8(2), 147 - 9
Investigation of the in vitro activity of streptomycin against Mycobacterium tuberculosis; Ruiz P et al.; Streptomycin was the first antibiotic used against Mycobacterium tuberculosis . It was used for years in monotherapy regimens, leading to the emergence of resistance; therefore, its use gradually waned . Given the resistance rates detected with current antituberculosis drugs, the use of streptomycin has gained renewed interest . The mechanism of action of streptomycin is inhibition of protein synthesis of mycobacteria in the ribosome . Resistance emerges when mutations appear in genes encoding 16S rRNA and protein S12 . The activity of streptomycin against 1,496 M . tuberculosis strains was investigated; 1,186 and 196 strains corresponded to pulmonary and extrapulmonary specimens, respectively . For 114 strains, the source was not indicated . Initially, the BACTEC 460 TB system was used for antibiotic susceptibility testing . Since 1996, the ESP II system was used . The strains ATCC27294 (sensitive to streptomycin, rifampin, ethambutol, and isoniazid) and ATCC35820 (resistant to streptomycin) were used as controls . An overall resistance rate of 2.2% was obtained . In all cases secondary resistance was observed . Multiresistance was observed in 23 strains.

Curr Opin Rheumatol, 2002 Jul, 14(4), 388 - 93
Development of autoimmunity in Lyme arthritis; Guerau-de-Arellano M et al.; Treatment-resistant Lyme arthritis (TRLA) develops in 10% of Lyme arthritis patients and is characterized by continuous joint inflammation that does not resolve with antibiotic therapy . TRLA is associated with HLA-DRB1*0401 and related alleles, as well as with an immune response to the Borrelia burgdorferi (Bb) outer surface protein A (OspA) . The immunodominant epitope of OspA in the context of HLA-DRB1*0401 corresponds to amino acids 165-173 (OspA165-173) . The human Lymphocyte Function Antigen-1 (hLFA1alpha) contains a peptide with homology to OspA165-173 . Treatment-resistant Lyme arthritis patients' T cells, cloned based on their ability to bind OspA165-173-loaded HLA-DRB1*0401 tetramers, respond to OspA and hLFA1alpha with a different cytokine profile, suggesting that hLFA1alpha acts as a partial agonist with a potential role in the perpetuation of joint inflammation.

MMW Fortschr Med, 2002 May 30, 144(22), 24 - 8
{Early diagnosis of Lyme borreliosis . Do not look only for erythema migrans}; Hofmann H; Although the typical erythema migrans is a relatively easy-to-recognize manifestation of Lyme borreliosis, it is by no means the sole cutaneous manifestation of infection with borreliae . In particular the early stages of the disease, with their paucity of symptoms or wide variability of the clinical symptomatology, often present a diagnostic challenge . This means that in the event of unclear unspecific cutaneous lesions indicating, for example, erysipelas or urticaria, Lyme borreliosis should also receive differential diagnostic consideration . Culture of the organism, DNA-based confirmation of B . burgdorferi or, where indicated, a serological investigation can confirm the diagnosis at an early stage . The treatment of choice compromises an antibiotic administered for an adequate duration and at an adequate dose, e.g . doxycycline 2 x 100 mg over three weeks) . If treatment is initiated in a local or disseminated early stage, healing rates of more than 85% can be achieved.

Med Pediatr Oncol, 2002 Aug, 39(2), 77 - 85
Evolving concepts of management of febrile neutropenia in children with cancer; Orudjev E et al.; BACKGROUND: Recent investigations of febrile neutropenia in pediatric cancer patients have identified subsets of low-risk patients who can be managed with less antibiotic therapy than previously recommended standards . METHODS AND MATERIALS: PubMed and Medline were searched for prospective trials and reviews of febrile neutropenia in children . Magnitude and duration of fever and neutropenia, comorbidities, and therapeutic strategies were examined . RESULTS: Twenty-seven prospective trials and five reviews were identified . The child with cancer and low-risk febrile neutropenia is clinically well and afebrile within 24-96 hr of antibiotic therapy and has evidence of marrow recovery with a rising phagocyte count . Disqualifying comorbidities include leukemia at diagnosis or in relapse, uncontrolled cancer, age under 1 year, medical condition(s) that would otherwise require hospitalization and social or economic conditions that may potentially compromise access to care or compliance . Therapeutic strategies include parenteral or oral antibiotics in the hospital with early discharge or parenteral antibiotics in the outpatient setting followed by oral or parenteral therapy and daily reassessment . Although as many as 25% of low-risk patients require modification of therapy and/or hospitalization, life-threatening or fatal infection is exceptional . CONCLUSION: One-third to one-half the children with febrile neutropenia are at low-risk of serious infection . In the context of clinic trials, they can be safely managed with inpatient or outpatient strategies that maintain close follow-up and reduce the burden of antibiotic therapy . Adoption of these alternative strategies as the standard of care should proceed with caution guided by written protocols .

J Biomed Mater Res, 2002 Sep 5, 61(3), 458 - 65
Biocompatibility and in vivo gentamicin release from bioactive sol-gel glass implants; Meseguer-Olmo L et al.; Biomaterial pieces, with suitable osteogenic properties for use in the treatment of bone defects and the capability to avoid bone infections, have been synthesized . These materials are composed exclusively of gentamicin sulfate and bioactive SiO(2)-CaO-P(2)O(5) sol-gel glass (previously synthesized) . Implant processing was achieved by uniaxial and isostatic pressure of the components mixture . After implanting the pieces into rabbit femur, we studied (i) the antibiotic release, determining the concentration in proximal and distal bone, liver, kidney, and lung as a function of time; and (ii) the bone growth resulting from the glass reactivity in the biologic environment . The results indicate that the implants are good carriers for local gentamicin release in the osseous tissue, exhibiting excellent biocompatibility and bone integration . Moreover, these implants are able to promote bone growth during their resorption process .

J Chromatogr B Analyt Technol Biomed Life Sci, 2002 Aug 5, 775(2), 127 - 32
New and rapid fully automated method for determination of tazobactam and piperacillin in fatty tissue and serum by column-switching liquid chromatography; Trittler R et al.; A sensitive and rapid HPLC assay for determining tazobactam and piperacillin in fatty tissue and serum is described . While the common methods need liquid-liquid extraction before the injection in a automated column switching HPLC, the new method works by direct injection of the filtered tissue extract or diluted serum in a automated column switching HPLC without any other pre-treatment . This was performed by the use of a NH2-precolumn and enrichment/transfer at different pH-level . During the analyses, the NH2-precolumn was automatically regenerated with acetonitrile-water . The chromatogram peaks for piperacillin and tazobactam were identified by the retention time and quantified by peak area . The calibration curve was linear between 1 and 16 microg/ml . The quantification limit of tazobactam was about 1 microg/ml in fatty tissue extracts and in diluted serum (calculated for pure serum 2 microg/ml), respectively . For piperacillin it was less . The described procedure allows sample clean-up and determination of the antibiotic within 35 min . The chromatograms with this easy sample treatment had the same quantity of matrix peaks and in contrast to liquid-liquid extraction no loss of piperacillin . Because of the automatically rinsing of the NH2-precolumn during the chromatographic separation, more than 50 different biological samples could be measured with one NH2-precolumn without loss of performance .

Synapse, 2002 Sep 1, 45(3), 200 - 5
Inhibition of autonomic nerve-mediated inotropic responses in guinea pig atrium by bafilomycin A; Hong SJ; Neurosecretory vesicles actively accumulate neurotransmitter by consuming proton motive force generated by vacuolar H+-ATPase (V-ATPase) . The effects of bafilomycin A, a macrolide antibiotic that inactivates V-ATPase, on nerve stimulation-mediated inotropic responses of the left atrium were studied to explore the role of the enzyme in the cholinergic and adrenergic neurotransmissions . On field stimulation, the contractility of paced atrium exhibited initial atropine-sensitive depression followed by propranolol-sensitive facilitation . Both the negative and positive inotropic effects were abolished by bafilomycin A . The inhibitions were irreversible and followed a similar time course and the inhibitory effects were accelerated by intense nerve stimulation . In contrast, bafilomycin A had no effect on the inotropic responses produced by muscarinic acetylcholine or alpha-adrenergic receptor agonist . Stimulation of neuronal nicotinic acetylcholine receptor also elicited biphasic changes of contractile force, which were depressed by bafilomycin A . Compared with the inhibitory effects on field stimulation, the depressions progressed slowly and incompletely . The results suggest that inhibition of V-ATPase depressed the synaptic transmissions at autonomic nerve-muscle junctions . Furthermore, bafilomycin A preferentially inhibited neurotransmitter release emanating from the immediately releasable pool .

BMC Health Serv Res . 2002 Jul 11;2(1):13.
Application of the development stages of a cluster randomized trial to a framework for valuating complex health interventions; Loeb MB; INTRODUCTION: Trials of complex health interventions often pose difficult methodologic challenges . The objective of this paper is to assess the extent to which the various development steps of a cluster randomized trial to optimize antibiotic use in nursing homes are represented in a recently published framework for the design and evaluation of complex health interventions . In so doing, the utility of the framework for health services researchers is evaluated . METHODS: Using the five phases of the framework (theoretical, identification of components of the intervention, definition of trial and intervention design, methodological issues for main trial, promoting effective implementation), corresponding stages in the development of the cluster randomized trial using diagnostic and treatment algorithms to optimize the use of antibiotics in nursing homes are identified and described . RESULTS: Synthesis of evidence needed to construct the algorithms, survey and qualitative research used to define components of the algorithms, a pilot study to assess the feasibility of delivering the algorithms, methodological issues in the main trial including choice of design, allocation concealment, outcomes, sample size calculation, and analysis are adequately represented using the stages of the framework . CONCLUSIONS: The framework is a useful resource for researchers planning a randomized clinical trial of a complex intervention.

Int J Qual Health Care, 2002 Jun, 14(3), 175 - 81
The Leeds University Maternity Audit Project; Wilson B et al.; OBJECTIVES: To measure levels of and changes in compliance with evidence-based recommendations in obstetrics in the UK . To identify barriers to and factors associated with compliance . DESIGN: A quantitative case-note audit for 1988 and 1996, and a qualitative interview study of key staff . SETTING: Twenty maternity units, selected at random from all UK units SUBJECTS: Fifty consecutive cases of pre-term delivery (PTD), Caesarean section (CS), instrumental delivery (ID), and perineal repair (PR) operations in each period in each unit . The lead clinician, midwifery manager, a senior midwife, neonatologist, and middle-grade obstetrician in each unit . MAIN OUTCOME MEASURES: Maternal steroid use in PTD, antibiotic use in CS, use of the ventouse (vacuum extractor) rather than forceps as instrument of first choice for ID, and use of polyglycolic acid (PGA) sutures for PR in each time period . Facilities for implementing, staff attitudes to, and the degree of planning to follow each recommendation . MAIN RESULTS: The median proportion of ventouse as instrument of first choice in each unit was 8% (range 0-32%) in 1988, rising to 64% (range 0-98%) in 1996 . PGA use for PR was 0% (range 0-30%) in 1988, and 72% (range 0-100%) in 1996 . Steroid use for eligible PTD was median 0% (range 0-23%) in 1988, rising to 82% (range 63-95%) in 1996 . Antibiotic use for CS was 7% (range 0-25%) rising to 84% (range 10-100%) in 1996 . There was no relationship between unit size, type of unit, facilities, staff attitudes or degree of planning, and compliance with the recommendations, nor was the level of adherence to one standard typically correlated with adherence to the others . However, there was a positive correlation (R = 0.6, P < 0.005) between local availability of the Cochrane database of perinatal trials and unit compliance with the audit standards in the latter time period . CONCLUSIONS: We have documented a massive shift in practice in line with the evidence, although many units still have substantial room for improvement . About 2000 wound infections, 200 deaths due to prematurity, nearly 8000 women in pain from catgut sutures, and 1500 cases of severe perineal trauma from forceps remain preventable . The reasons why units vary remain obscure, although the qualitative interviews often revealed local factors such as key enthusiastic staff . There was no sign of evidence being positively driven into practice by any systematic managerial process . The relationship between Cochrane availability and high-standard care may be simply a marker of commitment to the evidence, but it remains plausible that if senior staff make Cochrane available for their juniors, audit compliance improves.

Przegl Lek, 2002, 59 Suppl 1, 46 - 9
{Evaluation of diagnostic value of procalcitonin (PCT) as a marker of congenital infection in newborns}; Czyzewska M et al.; Systemic bacterial infections still remain one of the major causes of neonatal morbidity and mortality . Early detection of neonatal sepsis can be difficult, because the first signs of the disease may be unspecific and similar to symptoms of other non-infectious processes . Procalcitonin became a new, sensitive marker of bacterial infections in newborns . The aim of our study was to assess the value of PCT as a diagnostic and prognostic tool of neonatal maternofetal infections . We also tried to estimate normal ranges of PCT in uninfected newborns . MATERIAL AND METHODS: 74 newborns, born in the Department of Obstetrics and Gynaecology, University of Medicine of Wroclaw, then hospitalized in the Department of Neonatology entered the study . They were divided into 2 groups: group 1-29 neonates with recognized materno-fetal infection, group 2-45 newborns without infection . In both groups blood samples to measure PCT concentrations were obtained by venipuncture on the 1st, 2nd, 3rd, 5th and between the 10th and 14th day of life (in the group of infected neonates) Sera were stored at -40 degrees C before analysis . PCT was determined using an immunoluminometric assay (BRAHMS Diagnostica) . RESULTS: Serum procalcitonin values were significantly higher in the infected group than in the uninfected neonates (p < 0.001) . The most significant differences were noted on the 2nd and 3rd day of life (p < 0.0001) . After the treatment had been finished, the PCT levels in both groups were not statistically different . CONCLUSIONS: PCT is a useful tool in early diagnosing and monitoring the course of early-onset infections in neonates, particularly when blood cultures obtained from neonates remain negative . The decreasing concentrations of PCT level in children treated due to infection, indicate successful treatment and may help one to take a decision on termination of antibiotic therapy.

J Bacteriol, 2002 Aug, 184(15), 4211 - 8
The unique tuf2 gene from the kirromycin producer Streptomyces ramocissimus encodes a minor and kirromycin-sensitive elongation factor Tu; Olsthoorn-Tieleman LN et al.; Streptomyces ramocissimus, the producer of elongation factor Tu (EF-Tu)-targeted antibiotic kirromycin, contains three divergent tuf-like genes, with tuf1 encoding regular kirromycin-sensitive EF-Tu1; the functions of tuf2 and tuf3 are unknown . Analysis of the tuf gene organization in nine producers of kirromycin-type antibiotics revealed that they all contain homologues of tuf1 and sometimes of tuf3 but that tuf2 was found in S . ramocissimus only . The tuf2-flanking regions were sequenced, and the two tuf2-surrounding open reading frames were shown to be oriented in opposite directions . In vivo transcription analysis of the tuf2 gene displayed an upstream region with bidirectional promoter activity . The transcription start site of tuf2 was located approximately 290 nucleotides upstream of the coding sequence . Very small amounts of tuf2 transcripts were detected in both liquid- and surface-grown cultures of S . ramocissimus, consistent with the apparent absence of EF-Tu2 in total protein extracts . The tuf2 transcript level was not influenced by the addition of kirromycin to exponentially growing cultures . To assess the function of S . ramocissimus EF-Tu2, the protein was overexpressed in Streptomyces coelicolor LT2 . This strain is a J1501 derivative containing His(6)-tagged EF-Tu1 as the sole EF-Tu species, which facilitated the separation of EF-Tu2 from the interfering EF-Tu1 . S . ramocissimus EF-Tu1 and EF-Tu2 were indistinguishable in their ability to stimulate protein synthesis in vitro and exhibited the same kirromycin sensitivity, which excludes the possibility that EF-Tu2 is directly involved in the kirromycin resistance mechanism of S . ramocissimus.

Biomaterials, 2002 Aug, 23(15), 3175 - 81
Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite-gelatin composite microspheres; Sivakumar M et al.; Composite microspheres have been prepared from bioactive ceramics such as coralline hydroxyapatite {CHA, Ca10(PO4)6(OH)2} granules, a biodegradable polymer, gelatin and an antibiotic, gentamicin . In our earlier work, we have shown a gentamicin release from CHA granules--chitosan composite microspheres . In the present investigation, an attempt was made to prepare the composite microspheres containing coralline hydroxyapatite and gelatin (CHA-G), which were prepared by the dispersion polymerization technique and the gentamicin was incorporated by the absorption method . The crystal structure of the composite microspheres was analyzed using X-ray powder diffractometer . The Fourier transformed infrared spectrum clearly indicated the presence of amide and hydroxyl groups in the composite microspheres . Scanning electron micrographs and optical micrographs show that the composite microspheres are spherical in shape and porous in nature . The particle size of composite microspheres was analyzed and the average size was found to be 16 microm . The thermal behavior of composite microspheres was studied using thermogravimetric analysis and differential scanning calorimetric analysis . The cumulative in vitro release profile of gentamicin from composite microspheres showed near zero order patterns.

J Leukoc Biol, 2002 Jul, 72(1), 147 - 53
Sorting of neutrophil-specific granule protein human cathelicidin, hCAP-18, when constitutively expressed in myeloid cells; Bulow E et al.; Neutrophil granulocytes carry storage organelles, e.g., azurophil and specific granules . Poorly understood are the mechanisms for retrieval from constitutive secretion followed by sorting for storage . Therefore, we asked whether the specific granule protein human cathelicidin (hCAP-18) could be sorted for storage in other granules when the biosynthetic window is widened to allow this . We observed that hCAP-18 was targeted for storage in lysosome-related organelles when expressed constitutively in the rat basophilic leukemia and the mouse promyelocytic (MPRO) cell lines . In addition, premature release of the antibiotic C-terminal peptide LL-37 was observed . Retention of hCAP-18 was diminished by induction of differentiation of MPRO cells . In conclusion, a specific granule protein with native conformation may be sorted for storage in lysosome-related organelles of myeloid cells and converted prematurely to a supposedly biologically active form.

J Mol Cell Cardiol, 2002 Jul, 34(7), 789 - 95
Maintenance of myocardial levels of vitamin A in heart failure due to adriamycin; Danelisen I et al.; The therapeutic use of adriamycin (doxorubicin), a potent antitumor antibiotic, is limited by the development of dose-dependent cardiomyopathy . Increased oxidative stress due to adriamycin is considered to play a role in the pathogenesis of this toxic effect . In this study, we examined the levels and redistribution of vitamin A (a potent non-enzymatic antioxidant) in adriamycin-induced cardiomyopathy in rats . Three weeks after the adriamycin (ADR) treatment, animals were hemodynamically assessed and different tissues were analyzed for total retinol (vitamin A), (3)H-radio-labeled retinol, retinol palmitate and vitamin E . At 3 weeks, animals in the ADR group were hemodynamically and clinically confirmed to be in heart failure . In the ADR group, total retinol levels in heart and plasma were unchanged . However, levels of the (3)H radio-labeled fraction of retinol were significantly increased in both organs suggesting increased turnover . In the liver, the levels of total retinol and retinol palmitate were significantly decreased, while the radio-labeled fraction of retinol was significantly increased suggesting mobilization of retinol from this organ . Alpha tocopherol (vitamin E) levels were found unchanged in hearts of the ADR animals, while its levels in the plasma and liver were significantly increased . Increased radio-labeled fraction, without any change in the total retinol in the heart, suggested that vitamin A is utilized more by the heart under increased oxidative stress due to adriamycin . Its levels in the plasma and the heart may have been maintained at the expense of the loss from the liver .

Dermatol Nurs, 2002 Jun, 14(3), 177 - 8, 181
Treatment of surgical wound dehiscence; Candido LC; Surgical exploration of cavities, sinuses, and specific antibiotic therapy are fundamental for the control fo cutaneous infection . Topical treatment will vary based on evaluation of the lesion, experience of the health care team, and the environment.

J Virol, 2002 Aug, 76(15), 7736 - 46
Cell clones selected from the Huh7 human hepatoma cell line support efficient replication of a subgenomic GB virus B replicon; De Tomassi A et al.; Tamarins (Saguinus species) infected by GB virus B (GBV-B) have recently been proposed as an acceptable surrogate model for hepatitis C virus (HCV) infection . The availability of infectious genomic molecular clones of both viruses will permit chimeric constructs to be tested for viability in animals . Studies in cells with parental and chimeric constructs would also be very useful for both basic research and drug discovery . For this purpose, a convenient host cell type supporting replication of in vitro-transcribed GBV-B RNA should be identified . We constructed a GBV-B subgenomic selectable replicon based on the sequence of a genomic molecular clone proved to sustain infection in tamarins . The corresponding in vitro-transcribed RNA was used to transfect the Huh7 human hepatoma cell line, and intracellular replication of transfected RNA was shown to occur, even though in a small percentage of transfected cells, giving rise to antibiotic-resistant clones . Sequence analysis of GBV-B RNA from some of those clones showed no adaptive mutations with respect to the input sequence, whereas the host cells sustained higher GBV-B RNA replication than the original Huh7 cells . The enhancement of replication depending on host cell was shown to be a feature common to the majority of clones selected . The replication of GBV-B subgenomic RNA was susceptible to inhibition by known inhibitors of HCV to a level similar to that of HCV subgenomic RNA.

Vestn Oftalmol, 2002 Mar-Apr, 118(2), 15 - 7
{Treatment of lacrimal duct diseases using low energy helium-neon laser}; Dushin NV et al.; Treatment of diseases of the lacrimal duct remains a pressing problem in ophthalmology . These diseases are responsible for 71-85.4% diseases in capable people . Sixty patients with chronic dacryocystitis with partially retained patency of the lacrimal duct were treated by He-Ne low-frequency laser ULF-01 (output power 6.10 mcWt, laser beam wave length 0.632 nm) . The patients received 3-5 min sessions twice a week, 5-8 sessions per course . Positive effect was attained in 56 patients: complete cessation of excessive lacrimal discharge in 38 patients and subjective improvement in 18 . He-Ne laser exposure brings about a good antiinflammatory effect; in combination with antibiotic therapy it promotes rapid sanitization of the lacrimal duct, removes edema, and rapidly normalizes lacrimal discharge.

J Crit Care, 2002 Jun, 17(2), 114 - 21
Applying the science to the prevention of catheter-related infections; O'Grady NP; BACKGROUND: Catheter-related bloodstream infection (CR-BSI) remains a leading cause of nososcomial infection, despite the fact that many CR-BSIs are preventable . Simple principles of infection control and the use of novel devices to reduce these infections are not uniformly implemented . OBJECTIVE: To review and summarize the evidence that promotes strategies to prevent CR-BSIs . DATA SOURCES: The Medline database and bibliographies of review articles and book chapters were searched for relevant articles . STUDIES INCLUDED: In vitro and in vivo laboratory-based studies, controlled clinical trials, prospective interventional trials, and epidemiologic investigations . OUTCOME MEASURES: Reduction in CR-BSI, catheter colonization, tunnel infection, or local site infection . SYNTHESIS: The recommended prevention strategies with strong supportive evidence include educating and training of health care providers who insert and maintain catheters; using full barrier precautions during central venous catheter insertion; using a 2% chlorhexidine preparation for skin antisepsis; eliminating the practice of scheduled replacement of central venous catheters for prevention of infection; and using antiseptic/antibiotic impregnated short-term central venous catheters . CONCLUSION: Simple interventions can reduce the risk for serious catheter-related infection . Health care provider awareness and adherence to these prevention strategies is critical to reducing the risk for CR-BSI, improving patient safety, and promoting quality health care .

Am J Surg, 2002 Jun, 183(6), 608 - 13
Standardized patient care guidelines reduce infectious morbidity in appendectomy patients; Helmer KS et al.; BACKGROUND: Surgical wound infection and intra-abdominal abscess remain common infectious complications after appendectomy, especially in the setting of a perforated or gangrenous appendix . We therefore developed a clinical protocol for the management of appendicitis to decrease postoperative infectious complications . METHODS: Between January 1, 1999, and December 31, 1999, 206 patients with appendicitis were treated on protocol . Retrospectively, the charts were reviewed for all protocol patients as well as for 232 patients with appendicitis treated in the year prior to protocol initiation . Data were collected on surgical wound infections and intra-abdominal abscesses . RESULTS: There were significantly fewer infectious complications in the protocol group than in the nonprotocol group (20 {9%} versus 8 {4%}; P <0.05) . In patients with a perforated or gangrenous appendix, the infectious complication rate was reduced from 33% to 13% (P <0.05) . CONCLUSIONS: The incidence of infectious complications after appendectomy can be significantly reduced with a standardized approach to antibiotic therapy and wound management.

Hist Sci Med, 2002 Jan-Mar, 36(1), 11 - 20
{A forgotten discovery: doctor of medicine Ernest Duchesne's thesis (1874-1912)}; Pouillard J; It was only in 1946 that Ramon and Richou's publication in the newspaper "le Progres Medical", reminded of Ernest Duchesne's thesis which dealt for the first time with antagonism between germs and mould like penicillium . Thanks to Justin Godard's paper at the Academie de Medecine, Duchesne was known as "the precursor of the antibiotic action of penicillium" . From that moment, some papers were written and the thesis was even published in a luxurious edition . The 1983 year of the "Ecole du Service de Sante des Armees" was called Ernest Duchesne who can be considered as "the theoretician precursor of antibiotic therapy" according to Francois Chast.

Ann Chir, 2002 May, 127(5), 381 - 4
{Mesenteric venous thrombosis complicating acute appendicitis}; Germain MA et al.; Common primary surgical sources of thrombophlebitis of the mesenteric vein are diverticulitis and appendicitis . This is an acute ascending infection with septic thrombophlebitis . C.T . imaging can diagnose this complication at an early stage . Broad spectrum antibiotic therapy and heparin should be started . Surgery is performed electively to eradicate the primary inflammatory process . Early detections of septic ascending pylephlebitis and adequate treatment have decreased the mortality rate . We report a clinical case of thrombophlebitis of the mesenteric vein in acute appendicitis.

Vet Surg, 2002 Jul-Aug, 31(4), 303 - 8
Nasal dermoid sinus cysts in the dog; Anderson DM et al.; OBJECTIVE: To describe the clinical and morphologic characteristics of nasal dermoid sinus cysts in the dog . STUDY DESIGN: Retrospective clinical study . ANIMALS: Six client-owned dogs . METHODS: Medical records (1995 to 1999) of 6 dogs that had a discharging sinus in the midline of the nose removed surgically were reviewed for signalment, physical examination, surgical and histopathologic findings, and outcome . RESULTS: Three golden retrievers, 1 springer spaniel, 1 cocker spaniel, and 1 Brittany spaniel with a history of intermittent discharge from a small opening in the midline on the bridge of the nose at the junction between the nasal planum and the skin were identified . The condition was unresponsive to antibiotic therapy, and previous surgical excision had been unsuccessful in 3 dogs . None of the dogs had any other congenital defects, and all dogs responded to complete surgical excision of the tract and cyst . On histopathologic examination of excised tissue, there were adnexal structures along a tract lined with stratified squamous epithelium, consistent with a developmental abnormality of ectodermal tissue . CONCLUSIONS: The lesions were diagnosed as nasal dermoid sinus cysts, similar to the congenital condition described in humans . Nasal dermoid sinus cysts are rare developmental defects related to abnormal development of the pre-nasal space and may extend into the cranial vault causing cerebral abscesses or recurrent meningitis . Complete surgical excision has a good prognosis . CLINICAL RELEVANCE: This is a new condition that should be added to the surgical differential diagnosis for a discharging sinus over the external nares in dogs .

Klin Monatsbl Augenheilkd, 2002 May, 219(5), 349 - 52
{Primary diagnosis of syphilis by the ophthalmologist}; Porstmann AU et al.; BACKGROUND: Throughout the developed world the reported incidence of sexually transmitted diseases is rising with previously unreported cases at rates of 40 - 70 % . According to German sources, recent epidemiological data show a considerable increase of syphilis especially among homosexual men in larger cities . PATIENTS: We report on 4 patients (age 38 - 54) who were referred to our outpatient department because of vision loss of unknown origin . All were subsequently tested positive for syphilis . None of the patients (3 men, 1 woman) belonged to a risk group, only one described systemic symptoms (urethritis and arthritis) . The ocular manifestations of syphilis were broad: granulomatous and non-granulomatous anterior uveitis, papillitis, and chorioretinitis . Two patients also tested positive for HIV . After systemic antibiotic therapy, the ocular diseases stabilized . CONCLUSION: Diagnosis and therapy of syphilis is cost-effective . The rise of syphilis especially in urban areas necessitates a high level of suspicion dealing with patients with intraocular inflammation of unknown origin . Lues serology should be incorporated into routine lab diagnostics to aid in the detection of such cases.

EMBO J, 2002 Jul 1, 21(13), 3557 - 67
Cryo-EM reveals an active role for aminoacyl-tRNA in the accommodation process; Valle M et al.; During the elongation cycle of protein biosynthesis, the specific amino acid coded for by the mRNA is delivered by a complex that is comprised of the cognate aminoacyl-tRNA, elongation factor Tu and GTP . As this ternary complex binds to the ribosome, the anticodon end of the tRNA reaches the decoding center in the 30S subunit . Here we present the cryo- electron microscopy (EM) study of an Escherichia coli 70S ribosome-bound ternary complex stalled with an antibiotic, kirromycin . In the cryo-EM map the anticodon arm of the tRNA presents a new conformation that appears to facilitate the initial codon-anticodon interaction . Furthermore, the elbow region of the tRNA is seen to contact the GTPase-associated center on the 50S subunit of the ribosome, suggesting an active role of the tRNA in the transmission of the signal prompting the GTP hydrolysis upon codon recognition.

Clin Diagn Lab Immunol, 2002 Jul, 9(4), 795 - 801
Value of microimmunofluorescence for diagnosis and follow-up of Bartonella endocarditis; Fournier PE et al.; Bartonella endocarditis is a disease of emerging importance that causes serious complications and high rates of mortality . Due to the fastidious nature of Bartonella species and their high degrees of antibiotic susceptibility, cultures of clinical samples most often remain sterile and valvular biopsy specimens, the best specimens for PCR amplification, are seldom available . Therefore, serology appears to be the easiest diagnostic tool . In order to determine the best cutoff value for serology and its predictive values for the detection of Bartonella endocarditis, we studied 48 patients with culture- and/or PCR-confirmed Bartonella endocarditis . We also applied these serological criteria to 156 patients with blood culture-negative endocarditis . Furthermore, we compared the kinetics of the antibody responses to Bartonella spp . in order to estimate the value of serology for prediction of the occurrence of relapses . A titer of > or = 1:800 for immunoglobulin G antibodies to either Bartonella henselae or B . quintana has a positive predictive value of 0.810 for the detection of chronic Bartonella infections in the general population and a value of 0.955 for the detection of Bartonella infections among patients with endocarditis . When this cutoff was applied to 156 patients with blood culture-negative endocarditis, we were able to diagnose Bartonella infections in an additional 45 patients with definite endocarditis for whom a positive Bartonella serology was the only evidence of infection . On follow-up, the kinetics of the decrease in antibody titers were significantly delayed in two patients with relapses . In conclusion, we recommend the determination of antibodies to both B . quintana and B . henselae and the use of a cutoff value of 1:800 for the diagnosis of Bartonella endocarditis . We propose that this criterion, which may also help with the detection of late relapses, be included as a major criterion in the Duke criteria for the diagnosis of infective endocarditis.

J Pediatr Endocrinol Metab, 2002 May, 15 Suppl 2, 731 - 5
Growth problems and growth hormone treatment in children with cystic fibrosis; Hardin DS; Children with cystic fibrosis (CF) typically demonstrate poor linear growth and, despite aggressive nutritional supplementation, suboptimal weight gain . Growth velocity may be particularly blunted during puberty, a finding that occurs independently of clinical status or sex steroid levels . Several studies indicate that growth hormone (GH) treatment may be associated with significant improvement in both height velocity and weight gain in children with CF . These findings may translate into improvements in clinical status . In our experience, improved growth and weight status have been associated with fewer hospitalizations, fewer antibiotic courses, and improved pulmonary function . A large multicenter trial is currently underway to assess the effect of long-term therapy with GH on the quality of life and pulmonary status.

Rev Med Chir Soc Med Nat Iasi, 2001 Oct-Dec, 105(4), 803 - 5
{Chronic dacryocystitis fistulization in a Rubinstein-Taybi syndrome}; Costin D et al.; The article presents the treatment difficulties of the chronic dacryocystitis at an eight month old patient, diagnosed with Rubinstein-Taybi syndrome . The difficulties occurred as a result of numerous antibiotic treatments and surgical procedures suffered by the patient since his second week of life.

Rhinology, 2002 Jun, 40(2), 80 - 2
Incidence of chronic hyperostotic rhinosinusitis in patients undergoing primary sinus surgery compared to revision surgery; Kacker A et al.; HYPOTHESIS: The incidence of chronic hyperostotic rhinosinusitis has been underreported due to poor recognition of the disease process . The surgical management of chronic hyperostotic rhinosinusitis with prolonged pre and post-operative antibiotic therapy can alter clinical course of the disease process . STUDY DESIGN: A prospective study of 40 patients based at two teaching tertiary care institutions . MATERIAL AND METHODS: CT scans of twenty patients (ten undergoing primary sinus surgery and ten undergoing revision sinus surgery) were randomly selected from each institution and reviewed by an independent radiologist for evidence of hyperostosis and compared to original reading of the CT scans . RESULTS: The finding of sinus hyperostosis is rarely reported by the radiologist on the sinus CT scan where the focus is always on mucosal disease . The incidence of sinus hyperostosis is higher, in patients undergoing revision sinus surgery than patients undergoing primary sinus surgery . CONCLUSION: Sinus hyperostosis is not an uncommon finding in chronic refractory sinusitis which may require long term intravenous antibiotic therapy in conjunction with surgery to provide symptomatic relief.

Rev Med Chir Soc Med Nat Iasi, 2000 Apr-Jun, 104(2), 125 - 30
{Comparison on the effects of metronidazole in subgingival application in the treatment of adult periodontitis}; Martu S et al.; Control of subgingival plaque is the key of the treatment of periodontal diseases . The use of subgingival sustained-release antibiotic therapy is advocated for the beneficial effect on anaerobic flora . A single-blind clinical trial was carried out in 13 patients with adult periodontitis to compare the effects of subgingival application of metronidazole dental gel with those of subgingival scaling . METHOD AND MATERIALS: A split mouth design was used so that each patient received all treatments simultaneously . Randomly selected quadrants were treated with applications of 25% metronidazole gel, subgingival scaling, or a combination of scaling and gel application . The remaining quadrant in each patient was left untreated as a control . RESULTS: All three treatments were effective in significantly reducing bleeding on probing over the 14 weeks observation period . No statistically significant differences were found between scaling alone and combined treatment . Scaling and combined treatment were better than metronidazole . Metronidazole produced transient effects, best noted during the first 4 weeks after treatment . No additive effect of metronidazole was noted in the combined treatment . At week 14, only combined treatment sites and scaled showed statistically greater probing depths reduction than control sites . CONCLUSION: For the treatment of mild to moderate adult periodontitis, subgingival scaling alone is as effective as the combination of scaling and antibiotic therapy.

Rev Med Chir Soc Med Nat Iasi, 2000 Oct-Dec, 104(4), 153 - 5
{Difficulties in the diagnosis of prolonged fever in infants}; Miftode E et al.; We report the case of an infant with cytomegalovirus (CMV) infection who developed a nosocomial sepsis of mixed etiology . Fever failed to decrease despite long-time and sustained antibiotic therapy . Treatment with an antiviral agent following the detection of CMV antibody of the IgM class resulted in clinical improvement and subsequent full recovery . We suggest that the diagnosis of CMV infection should be considered even in immunocompetent patients in whom antibiotic therapy fails.

Rev Med Chir Soc Med Nat Iasi, 2000 Jul-Sep, 104(3), 77 - 81
Ender nailing versus external fixation in the stabilization of type III open tibial shaft fractures; Cozma T et al.; Management of severe open tibial shaft fractures presents a difficult challenge to the orthopaedic surgeon . They are frequently associated with loss of limb, infection and high levels of morbidity . All the authors considered, now, that there are five keys to successful treatment: antibiotic therapy, radical debridement and pulsed lavage irrigation, stabilization of fracture with minimal further devascularization, early soft tissue coverage and early bone-grafting . It rests, also, a number of controversies in the management of open tibial fractures, not least of which is the method of fracture stabilization: the choice between intramedullary nailing and external skeletal fixation, the use of reamed or unreamed nails . MATERIAL AND METHODS: Fifty-seven patients with 62 open fractures of the tibial shaft type IIIA, B and C (Gustilo) were treated between 1.01.1994 and 31.12.1998 in the Department of Orthopaedic Surgery of the Emergency Hospital, Iasi, Romania . There were 29 cases type IIIA fractures, 26 cases type IIIB and 7 cases type IIIC (Mess score showed the viability of the limb) . Our patients were 36 males and 21 females; their mean age was 36 years (range 17 to 70) . Forty-six patients were injured in road traffic accidents and 11 in other traumatic incidents . In 33 cases the skeletal stabilization was achieved by Ender nailing under general or regional anesthesia . In 15 cases we used a bilateral uniplanar external fixator (Burghele) and 14 fractures were stabilized with an Ilizarov external fixator . We note a secondary amputation after the failure of the revascularization of the limb in a type IIIC fracture . RESULTS: All fractures united; the mean time to union was 30.2 weeks--in the external fixation group and 26.4 weeks--in the Ender nailing group . Malunions occurred slightly more frequently in the external fixation group that in the Ender nailing group (15.7% versus 5.8%) . We noted--also--more secondary procedures required in the external fixation group . The infection rate was 3 of 33 (9.1%) in the Ender nailing group compared to 4 deep (13.8%) and 8 pin-tract infection (27.6%) in the external fixation group . CONCLUSIONS: Our study suggests that Ender nailing has several advantages over external fixation in the management of severe open tibial shafts fractures . Based on these results, over the last years, in our Department we use mainly the Ender nailing technique, as we consider it a better approach for these type of lesions.

Ann Diagn Pathol, 2002 Jun, 6(3), 194 - 203
Blastomycosis: The great pretender can also be an opportunist . Initial clinical diagnosis and underlying diseases in 123 patients; Lemos LB et al.; Clinically, blastomycosis can be difficult to recognize even in the endemic areas where clinicians are aware of this problem . In only 18% of 123 patients from the University of Mississippi Medical Center (Jackson, MS) blastomycosis was correctly suspected at the initial patient evaluation . Pneumonia sensu latu (40%), malignant tumors (16%), and tuberculosis (14%) were the most common misdiagnoses . The false first impression frequently resulted in unnecessary surgeries or treatment delays, with patients receiving inefficient antibiotic therapy for months . The presence of cutaneous involvement by the disease makes its' recognition easier for the clinician, raising the percentage of correct initial diagnosis to 64% . To evaluate the association with immunodepression, the presence of other diseases was also searched among the 123 patients . An immunodepressive condition preceded the fungal disease in 25% of patients . Another associated disease commonly found in blastomycotic patients was diabetes mellitus (22%) . Blastomycosis is correctly suspected at the first clinical evaluation in only a small percentage of patients; pneumonia, cancer, and tuberculosis are the most common clinical considerations . Cutaneous involvement leads the clinician to the correct diagnosis in the majority of cases . One fourth of the patients with blastomycosis had underlying immunodepressive conditions, and underlying diabetes mellitus is present in 22% of patients .

J Infect Dis, 2002 Jul 1, 186(1), 134 - 7 Epub 2002 Jun 10.
Prophylactic administration of liposomal amphotericin B is superior to treatment in a murine model of invasive aspergillosis after hematopoietic cell transplantation; BitMansour A et al.; With use of a novel model of invasive Aspergillus fumigatus, the efficacy of prophylactic versus therapeutic administration of liposomal amphotericin B (L-AmB) was tested in C57BL/6 mice . After lethal irradiation and transplantation of whole bone marrow (d 0), animals were challenged with conidia either intravenously or via nasal instillation on d +3 and divided into 3 groups: group I received 5% dextrose in water throughout the study period; group II received L-AmB, 5 mg/kg, beginning on d +4; and group III received L-AmB, 5 mg/kg on d -4, d -2, d 0, and d +2, then daily starting d +4 . Groups I and II did not survive intravenous challenge, whereas group III had a 40% survival rate . After nasal instillation of conidia, the survival was 25%, 35%, and 85% for mice in groups I, II, and III, respectively . These results demonstrate that prophylactic administration of L-AmB increased early survival against lethal challenge with A . fumigatus, compared with therapy instituted after infection.

Folia Med (Plovdiv), 2001, 43(4), 40 - 5
Fluoroquinolone prophylaxis for bacterial infections in neutropenic patients with hematologic malignancies; Nenova IS et al.; INTRODUCTION: The use of fluoroquinolones as prophylaxis for bacterial infections in patients with chemotherapy induced neutropenia is debatable . The present study was conducted to assess the prophylactic efficacy of fluoroquinolones in adult neutropenic patients with hematologic malignancies . MATERIALS AND METHODS: For the period 1994 through 2000 a prospective, randomized trial was conducted at the University Clinic of Hematology (Medical University, Plovdiv) . Two groups of patients were included--experimental group, consisting of 36 patients with 41 granulocytopenic episodes and a control group of 34 patients with 41 granulocytopenic episodes . Non parametrical and psi methods were used for statistical analysis . Kaplan-Meier test was employed to determine patients' survival rate . Comparison of survival rates between the two groups was performed using the log-rank test . RESULTS: A statistically significant difference between the two groups was found in the number of infection-free neutropenic episodes (P < 0.001), in infection-related mortality rate (p = 0.001) and mortality rate within 1 month of the onset of infection (p < 0.001) . Difference in long term survival rates was not statistically significant (p > 0.05) . CONCLUSIONS: Prophylaxis with fluoroquinolones reduced the occurrence of infection in adult neutropenic patients without affecting the long-term survival . Moreover, it is especially beneficial for patients with severe neutropenia and during the active phase of the disease.

Antibiot Khimioter, 2002, 47(2), 24 - 8
{Perioperative management of focal liver diseases by ofloxacin}; Khlebnikov EP et al.; Perioperative use of ofloxacin for prophylaxis was investigated in 20 patients with focal hepatic formations (hemangioma, adenocarcinoma, echinococcosis) . First dose of ofloxacin (200 mg) was given intravenously 15 min before operation . After operation ofloxacin was used intravenously (400 mg daily) for 5 days . Pharmacokinetic investigation demonstrated that perioperative intravenous use of ofloxacin provided concentrations in blood and hepatic tissue satisfactory for potential microflore inhibition . Immunological monitoring demonstrated positive dynamics on 5-7 days after operation . dynamics depended on nosology of the focal hepatic formation . Ofloxacin use for prophylaxis in the operated patients with focal hepatic formations was efficient for profilaxy of postoperation infective complications.

Clin J Oncol Nurs, 2002 Jul-Aug, 6(4), 198 - 205
Granulocyte macrophage colony-stimulating factor: current practice and novel approaches; Buchsel PC et al.; Endogenous myeloid colony-stimulating factors (CSFs) have demonstrated the ability to enhance the clinical management of immunosuppressed patients with cancer . These agents are associated with significant decreases in chemotherapy-associated infections, antibiotic use, length of hospital stays, and mortality . Two major endogenous recombinant myeloid CSFs currently are being manufactured . Granulocyte macrophage CSF (GM-CSF) (sargramostim, Leukine, Immunex Corporation, Seattle, WA) has broad activity in the proliferation and differentiation of myeloid lineage progenitor cells, whereas granulocyte CSF (filgrastim, Neupogen, Amgen, Inc., Thousand Oaks, CA) acts selectively on cells of the granulocyte lineage . Clinical trials suggest that GM-CSF has clinical benefits beyond enhancing neutrophil recovery, including shortening the duration of mucositis and diarrhea, stimulating dendritic cells, preventing infection, acting as an adjuvant vaccine agent, and facilitating antitumor activity.

Otolaryngol Head Neck Surg, 2002 Jun, 126(6), 614 - 22
Rhinosinusitis treatment protocol: changing provider habits in primary care; Kinney WC; OBJECTIVE: Sinus infections are common and represent a high cost to the health care industry . Clinical protocols can be used to develop cost-effective treatment strategies . Our objective was to show that a protocol for rhinosinusitis can change provider practice patterns in primary care . STUDY DESIGN AND SETTING: We used a literature search, survey of primary caregivers, and chart review from an academic health center to define and document current patterns . A protocol was developed and evaluated using the Rhinosinusitis Disability Index . RESULTS: Survey and chart review identified that primary caregivers do not elicit a detailed history for rhinosinusitis . Protocol use increased this to 100% . First-line antibiotic therapy was used for only 49.4% of the patients before protocol use and for 68.5% after protocol use . Patients felt better after treatment 84.1% of the time; the Rhinosinusitis Disability Index could not measure improvement . CONCLUSION: Provider practice patterns were positively influenced by use of the protocol . SIGNIFICANCE: Clinical protocols should be developed to direct provider treatment practices.

Lancet, 2002 Jun 15, 359(9323), 2078 - 83
Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease; Biedermann BC et al.; BACKGROUND: Vascular endothelial cells form the interface between recipient tissues and circulating alloreactive donor T cells after allogeneic stem cell transplantation . Vascular injury has been seen in patients with acute graft versus host disease (GVHD) in the skin . We aimed to see whether vascular injury mediated by cytotoxic T lymphocytes and microvessel loss arises in patients with chronic GVHD . METHODS: We investigated eight patients with acute GVHD and ten with chronic GVHD for signs of endothelial injury and microvessel loss by measurement of von Willebrand factor (vWF) in plasma and blood vessel density in biopsy samples taken from lesional skin . Controls consisted of nine patients without GVHD who survived for longer than 100 days and nine healthy people . Inflammation and endothelial injury were assessed in selected samples by immunostaining for CD8 T cells, activated cytotoxic T lymphocytes, and vascular endothelial cells . FINDINGS: We identified more extensive loss of microvessels in the skin of patients with GVHD (median 66 capillaries/mm(2); IQR 16-98) than of healthy controls (205 capillaries/mm(2); 157-226; p=0.005) . Patients with GVHD had higher concentrations of vWF (238%; 168-288) than did those without GVHD (102%; 88-118; p=0.0005) . Perivascular CD8 T cell infiltrates in skin correlated with vWF plasma concentrations in patients with GVHD (p=0.01), and activated cytotoxic T lymphocytes and endothelial injury were present in these same samples . INTERPRETATION: Host endothelial cells are a target of alloreactive donor cytotoxic T lymphocytes . Substantial blood vessel loss may lead to impaired blood perfusion and tissue fibrosis, the hallmark lesion of chronic GVHD.

Surg Endosc, 2002 Nov, 16(11), 1612 - 4 Epub 2002 Jun 27.
Thoracoscopic-assisted management of postpneumonic empyema in children refractory to medical response; Liu HP et al.; BACKGROUND: Empyema frequently complicates the hospitalization of children; and in advanced stages, it often requires surgical intervention . In this study, we investigated the use of video-assisted thoracic surgery (VATS) for the management of postpneumonic empyema in children who have had an unsatisfactory medical response . METHODS: We did a retrospective review of the medical records of 51 consecutive patients with loculated empyema (mean age, 5 years; range, 2 months to 15 years) hospitalized at Chang Gung Memorial Hospital between 1995 and 2000 . All patients underwent debridement of the necrotic lung tissue and evacuation of the loculated empyema cavity using a VATS approach . RESULTS: The mean operating time for the 51 patients was 90 min (range, 50-210); mean blood loss was 70 cc . Fever subsided within 72 h postoperatively in all patients . On average, chest tubing was removed on the 7th postoperative day (range, 4-18 days) . However, in one patient who suffered from a prolonged air leak, the chest tube was not removed until day 18 . The mean postoperative stay for all patients was 13.7 days (range, 9-23) . No deaths occurred, and all of the children made a good recovery . A follow-up revealed that one of the 51 children patient suffered a left upper lung abscess 7 months after discharge . Left upper lobectomy was performed in this case, and the patient was discharged uneventfully 10 days after the operation . CONCLUSIONS: VATS is a safe and effective treatment for pediatric empyema . Thoracoscopic-assisted surgery facilitates visualization, evacuation, and debridement of the necrotizing lung tissue . Early surgical intervention can avoid lengthy hospitalization and prolonged intravenous antibiotic therapy, and it can accelerate clinical recovery.

J Clin Gastroenterol, 2002 Jul, 35(1), 50 - 60
Evaluation of factors that have reduced mortality from acute pancreatitis over the past 20 years; Bank S et al.; BACKGROUND: The mortality associated with acute pancreatitis varies markedly in different studies, with most frequently reported mortality rates of 10% to 15% for all cases and 15% to 90% for attacks regarded as "severe." More recently, various centers have recorded lower mortality rates of 4% to 7% for all attacks of acute pancreatitis and 20% to 50% for those regarded as severe . GOALS: To investigate whether there has been a reduction in mortality associated with acute pancreatitis over the past 20 years and the reasons for this reduction . STUDY: Intended as a review, this study included the authors' 20-year prospective assessment of mortality as it relates to the severity of the disease, complications, and current therapy . For the mortality results, the study was divided into four 4-year periods from 1977 to 1998 and the past 3 years (i.e., 1998-2001) . For comparison, the mortality figures from some other large studies are presented . RESULTS: This study showed that the initial reduction in mortality related to acute pancreatitis coincided with the recognition and application of the signs of severity, either Ranson's prognostic signs or Bank's clinical criteria . These signs dictated admission to intensive care unit (ICU) therapy, the intensity of ICU monitoring, and the importance of organ-specific emergent therapy . Further mortality reduction in the 1990s could be attributed to either a more select study sample or earlier and more selective endoscopic or surgical debridement of infected tissue, endoscopic cyst drainage, and angiographic control of gastrointestinal bleeding . Improved nutritional support by jejunal feeding, earlier use of antibiotic therapy, gut sterilization, early endoscopic retrograde cholangiopancreatography for common bile duct stones and necrosectomy for noninfected necrosis have reduced the overall mortality associated with acute pancreatitis to a mean of 5% (range, 3.8-7%) for all cases and 20% (range, 15-25%) for severe cases . However, it is clear that the greater the number of signs denoting severity of organ failure, the higher the mortality . CONCLUSIONS: There has been considerable reduction in the mortality associated with acute pancreatitis over the past 20 years . The reasons are multifactorial, but recognition of severity signs, early implementation of organ-specific therapy, and newer endoscopic, surgical, and angiographic therapy for infection cyst and bleeding appear to have been the major factors in reducing mortality.

Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 1998, 16(1), 38 - 41
{Observation on the factors influencing infection rate of Meriones unguiculatus with Brugia malayi}; Xu D et al.; AIM: To explore the factors influencing the infection rate of M . unguiculatus with B . malayi . METHODS: The survival rate, infection rate and infection intensity were observed in M . unguiculatus infected with the infective larvae of B . malayi contained in normal saline, antibiotic, glucose or culture medium RPMI1640, respectively . RESULTS: The survival rate, infection rate and rate of infection intensity in normal saline group, antibiotic group, glucose group and RPMI1640 group were 80.9%, 60.5%, and 43.4%; 98.8%, 52.9% and 30.6%; 98.0%, 68.8% and 50.0%; 91.2%, 67.7% and 51.6%, respectively . The rate and the infection intensity were higher in the jirds infected with the 6th generation of Zhejiang strain than that with the 31st generation of Guizhou strain . CONCLUSION: The antibiotic was found to raise the living rate of the infected jirds, but reduce the infection rate and infection degree intensity; whereas glucose and culture medium RPMI1640 could raise the positive rate and the infectino . The jird was more susceptible to the 6th generation of Zhejiang strain than the 31st generation of Guizhou strain of B . malayi.

J Orthop Sci, 2002, 7(3), 370 - 8
Mechanical properties of the femur after injection of calcium phosphate cement containing arbekacin sulfate and polylactic acid in a rat model of experimental osteoporosis; Tanaka A et al.; We developed a calcium phosphate cement containing arbekacin sulfate and polylactic acid (CPC95AP) and examined its effects on bone strength by injecting the CPC95AP into the femoral medullary cavity in model rats with osteoporosis . Favorable cortical bone strength was maintained for more than 6 months when CPC95AP was injected into the femoral cavities . This phenomenon was more significant in the weakened femur of osteoporotic rats . The reasons for the increased bone strength are thought to be that the CPC95AP filling increased the geometric moment of inertia and that the binding of CPC95AP with the bones increased Young's modulus . The most important factor is believed to be the increased Young's modulus . The binding of CPC95AP with the bones after filling the femur cavities compensates for the weak extensional strength of CPC95AP, and provides an opportunity to utilize the compressive strength, which is the advantage of CPC95 . CPC95AP has antibiotic properties and biocompatibility, and it increases the mechanical strength of the weakened bone; therefore, it is considered useful in bone filling and stiffening.

Cochrane Database Syst Rev . 2002;(2):CD003153.
D-cycloserine for Alzheimer's disease; Laake K et al.; BACKGROUND: Evidence supports a role for the NMDA receptors in learning and memory . These can be modulated by the antibiotic D-cycloserine in such a way that the effect of the excitatory transmitter substance glutamate is enhanced . A study on healthy subjects pretreated with scopolamine to mimic Alzheimer's disease showed a positive effect of D-cycloserine at low doses . OBJECTIVES: To assess the efficacy and safety of D-cycloserine in patients with Alzheimer's disease . SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 14 June 2001 using the terms: cycloserine, D-cycloserine, Alzheimer* . SELECTION CRITERIA: Randomized, double-blinded and unconfounded trials comparing D-cycloserine with a control treatment . DATA COLLECTION AND ANALYSIS: Two larger and two smaller randomized controlled trials were identified . The clinical global impression scale was used in all studies and was a primary outcome measure . MAIN RESULTS: It was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies . There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose . The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25) . There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months . REVIEWER'S CONCLUSIONS: The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.

Cochrane Database Syst Rev . 2002;(2):CD002033.
Nystatin prophylaxis and treatment in severely immunodepressed patients; Gotzsche PC et al.; BACKGROUND: Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although the effect seems to be equivocal . OBJECTIVES: To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency . SEARCH STRATEGY: MEDLINE and The Cochrane Library using a comprehensive search strategy, date of last search November 2001 . Contacted industry and scanned reference lists . SELECTION CRITERIA: Randomised trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B . DATA COLLECTION AND ANALYSIS: Data on mortality, invasive fungal infection and colonisation were extracted by both authors independently . The outcomes were weighted by the inverse variance . A random effects model was used unless p>0.10 for the test of heterogeneity . MAIN RESULTS: We included 12 trials (1,464 patients) . The drugs were given prophylactically in ten trials and as treatment in two . Seven trials were in acute leukaemia, two in cancer, one in liver transplant patients, one in critically ill surgical and trauma patients, and one in AIDS patients . Nystatin had been compared with placebo in three trials and with fluconazole in nine; the dose varied from 1.5 MIE to 72 MIE daily . The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk 0.85, 95% confidence interval 0.65 to 1.13) . There was no statistically significant difference between fluconazole and nystatin on mortality (relative risk 0.76, 0.49 to 1.18) whereas fluconazole was more effective in preventing invasive fungal infection (relative risk 0.37, 0.15 to 0.91) and colonisation (relative risk 0.49, 0.34 to 0.70) . The results were very similar if the three studies which were not performed in cancer patients were excluded . REVIEWER'S CONCLUSIONS: Nystatin cannot be recommended for prophylaxis or treatment of Candida infections in immunodepressed patients.

Pediatr Infect Dis J, 2002 Apr, 21(4), 283 - 6
Impact of rapid polymerase chain reaction results on management of pediatric patients with enteroviral meningitis; Robinson CC et al.; BACKGROUND: Enterovirus (EV) infections can be rapidly detected by PCR . However, several studies suggest that results must be available early in the management of the patient to impact significantly on patient care . We evaluated this hypothesis directly during an outbreak of EV aseptic meningitis . METHODS: From June through November, 1998, EV PCR was performed 5 days a week on cerebrospinal fluid specimens from pediatric patients evaluated for meningitis . We compared antibiotic use, length of stay and hospital charges in a group of patients with EV meningitis whose positive EV PCR results were available within 24 h of specimen collection, to a group of similar patients whose results were available >24 h after collection . RESULTS: Cerebrospinal fluid specimens were submitted for EV PCR from 113 patients with suspected EV meningitis, and 50 of 113 (44%) were positive . Of these 50 EV-PCR-positive patients, 17 of 50 (34%) had EV PCR results available in < or = 24 h and 33 of 50 (66%) had results available in >24 h . Patients with EV-positive results reported < or = 24 h after specimen collection had 20 h less of antibiotic use (P = 0.006) and $2,798 less in hospital charges (P = 0.001) than patients with positive results available in >24 h . Hospitalized patients who received positive results rapidly did not have significantly less antibiotic therapy or shorter length of stay, but hospital charges were reduced by $2,331 (P = 0.009) . CONCLUSION: Rapid reporting of PCR results can have a significant impact on several outcome measures for patients with EV meningitis.

Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2000, 32(3), 229 - 234
Transcription and Translation of Sendai Virus Hemagglutinin-neuraminidase (HN) in Mammalian Cells; Hu JH et al.; Sendai virus hemagglutinin-neuraminidase was expressed in COS-7 cells . LLCMK(2) cells were transfected with expression plasmids harboring HN, namely pJH3, pJH4 or pJH7, and were passaged conti-nuously under the presence of hygromycin or puromycin to get antibiotic-resistant clones, which had HN gene integrated into genomes . S1 nuclease assay indicated that large quantity of HN mRNA was transcribed but indirect-immunofluorescence and immunoprecipitation demonstrated that there was little HN protein expressed on cell surface and inside cells, in contrast with the Sendai virus persistent-infected LLCMK(2) cells that expressed largely HN protein . Therefore, not every transcription resulted in translation . It also suggests that some virus factors may positively regulate transcription and translation of HN mRNA.

Int J Artif Organs, 2002 May, 25(5), 365 - 72
Various clinical approaches to minimise complications in peritoneal dialysis; Stegmayr B; The main reason for a failure of peritoneal dialysis is due to technical problems or infections . By starting PD immediately after the insertion of a dialysis catheter (instead of starting HD before optimal healing of the PD-catheter) it may be easier to achieve acceptance for PD by the patients . An easy and tight access is achieved when inserting the PD-catheter through the rectus muscle, fixing it with three purse string sutures, two of them fixing the inner cuff between the peritoneal membrane and the inner rectus fascia . Thereby early and late leakage will be rare and good drainage is normally achieved besides a low risk for exit site infections . Using Coloplast adhesive insulin can be injected into the PD bags in a simple way even by patients with bad vision . Using ultraviolet light, as additional exchange device (UV-box), the risk for peritonitis is reduced compared to classic manual connection . Using the Y-set or duo-bag system the risk for peritonitis is further lowered . Malfunction by dislocation of the intraperitoneal part of the catheters can often be corrected without surgery using a bent stylet . A controlled study showed that antibiotic prophylactics could significantly reduce the risk for peritonitis in the follow up after insertion of PD catheters . Additionally the risk for peritonitis is reduced using a special connector for the PET-sampling procedures . X-ray of catheter location in the abdominal cavity can be performed by injection of 20-ml contrast media into 100 ml of PD fluid residing in the PD-bag . After mixing, small portions of this fluid can be infused into the abdomen for X-ray determination of the location . An increased ultrafiltration failure during PD may be due to use of beta-blocker medication . After ceasing this medication recovery may occur . Avoiding pets in the room used for PD-exchange may lower the risk for peritonitis further . A devoted nurse and physician will keep up the patients' spirit and help to convert patients not suitable for PD to HD or the other way round . By such measures the incidence of peritonitis can be reduced to 1 in 40 treatment months or less.

Int J Clin Pract, 2002 May, 56(4), 287 - 91
Immunisation with a pneumococcal 7-valent conjugate vaccine; Dagan R; Pneumococcal disease causes approximately 1 million deaths a year worldwide in children aged younger than 5 years . Increasing antibiotic-resistant strains have made management of pneumococcal disease difficult . A pneumococcal 7-valent conjugate vaccine (PNCRM7) has been shown to prevent invasive disease in young children; it has also demonstrated a modest impact on the prevention of otitis media . This conjugated vaccine provides a consistent immune response in infants and young children and can be administered simultaneously with other childhood vaccines . It is generally well tolerated, with local reactions similar to those observed with other licensed childhood vaccines . The objective of this review is to discuss the clinical efficacy, immunogenicity and safety of PNCRM7.

In Vivo, 2002 Mar-Apr, 16(2), 111 - 6
Computer simulation of spermine-porin channel interactions; Vidal S et al.; Porin channels play a prominent role during fluoroquinolone uptake and spermine strongly alters the diffusion rate of norfloxacine . Consequently the interactions between spermine and bacterial porin were studied by computer simulation . The results indicate that various residues (E62, D 113, E 117,...) closely located in the internal eyelet region of the OmpF channel are potential binding sites . Among them, the D 113 residue, seems to play an important role in the association channel-spermine . This interaction introduces several changes in the internal morphology of the channel which are responsible for the inhibition of antibiotic uptake using the porin route.

Vet Parasitol, 2002 Jul 29, 107(1-2), 115 - 26
Effect of tetracycline on development of Anaplasma marginale in cultured Ixodes scapularis cells; Blouin EF et al.; Infections of the tick-borne ehrlichial pathogen, Anaplasma marginale, in cattle have been controlled, in part, by administration of low doses of tetracycline . Recently, a cell culture system was developed for A . marginale using a tick cell line derived from embryonic Ixodes scapularis . This study was designed to determine the effect of tetracycline on A . marginale propagated in a tick cell culture assay . Various concentrations of tetracycline (0, 0.01, 0.10, 1.0, 5, 10, 20 or 100 microg/ml) were added in medium to cultures 48h after cell monolayers were inoculated with A . marginale . A . marginale growth in the drug treated and control cultures was subsequently evaluated by indirect ELISA at 7 days post-infection (PI) and daily by light and electron microscopy (LM and EM) . Infectivity of the culture-derived A . marginale was determined by inoculation of susceptible cattle with treated and untreated control cultures . Tetracycline doses of 5, 10, 20 and 100 microg/ml resulted in significant inhibition of A . marginale growth as determined by ELISA . Morphologic deterioration of Anaplasma, as determined by LM and EM, occurred in cultures treated with the same drug concentrations . A . marginale replication, inhibited in cultures treated on days 2-6 PI with 20 microg/ml tetracycline, was not apparent 96 days after antibiotic removal . Infected cell cultures treated with medium containing 20 microg/ml tetracycline proved to be non-infective when inoculated into susceptible splenectomized calves . All parameters studied herein demonstrated that tetracycline killed A . marginale in cultured tick cells . The Anaplasma-tick cell culture drug assay therefore, would be useful for screening and evaluating novel antibiotics for control of anaplasmosis.

J Am Coll Nutr, 2002 Jun, 21(3 Suppl), 212S - 217S
Foods as production and delivery vehicles for human vaccines; Korban SS et al.; Vaccination is a great asset for eradication of infectious diseases in humans and animals . With the prevalence of antibiotic resistant bacterial strains and an alarming increase in new and re-emerging pathogens, the need for vaccination continues to be a high priority for mammalian diseases . In the last several years, a novel approach for developing improved mucosal subunit vaccines has emerged by exploiting the use of genetically modified plants . It has been demonstrated that plant-derived antigens are functionally similar to conventional vaccines and can induce neutralizing antibodies in mammalian hosts . Using genetically engineered plants for the production of immunogenic peptides also provides a new approach for the delivery of a plant-based subunit vaccine, i.e., oral delivery, provided these immunogenic peptides are expressed in an edible part of the plant, such as grain or fruit . Thus, food crops can play a significant new role in promoting human health by serving as vehicles for both production and delivery of vaccines.

Glycobiology, 2002 May, 12(5), 329 - 37
Shuttling of galectin-3 between the nucleus and cytoplasm; Davidson PJ et al.; In previous studies, we documented that galectin-3 (M(r) approximately 30,000) is a pre-mRNA splicing factor . Recently, galectin-3 was identified as a component of a nuclear and cytoplasmic complex, the survival of motor neuron complex, through its interaction with Gemin4 . To test the possibility that galectin-3 may shuttle between the nucleus and the cytoplasm, human fibroblasts (LG-1) were fused with mouse fibroblasts (3T3) . The monoclonal antibody NCL-GAL3, which recognizes human galectin-3 but not the mouse homolog, was used to monitor the localization of human galectin-3 in heterodikaryons . Human galectin-3 localized to both nuclei of a large percentage of heterodikaryons . Addition of the antibiotic leptomycin B, which inhibits nuclear export of galectin-3, decreased the percentage of heterodikaryons showing human galectin-3 in both nuclei . In a parallel experiment, mouse 3T3 fibroblasts, which express galectin-3, were fused with fibroblasts derived from a mouse in which the galectin-3 gene was inactivated . Mouse galectin-3 localized to both nuclei of a large percentage of heterodikaryons . Again, addition of leptomycin B restricted the presence of galectin-3 to one nucleus of a heterodikaryon . The results from both heterodikaryon assays suggest that galectin-3 can exit one nucleus, travel through the cytoplasm, and enter the second nucleus, matching the definition of shuttling.

Antimicrob Agents Chemother, 2002 Jul, 46(7), 2244 - 8
Pharmacodynamic effects of nitroimidazoles alone and in combination with clarithromycin on Helicobacter pylori; Svensson M et al.; Pharmacodynamic studies of Helicobacter pylori exposed to metronidazole and tinidazole alone and in combination with clarithromycin were performed by bioluminescence assay of intracellular ATP . The pharmacodynamic parameter control-related effective regrowth time (CERT) was used . CERT is defined as the time required for the resumption of logarithmic growth and a return of the level of growth to the preexposure inoculum in the test culture minus the corresponding time in the control culture . CERT measures the combined effects of the initial level of killing and postantibiotic effect . The incubation times and drug concentrations were chosen according to their half-lives and their clinically achievable concentrations . The study shows that the parameter CERT is useful for the testing of antibiotic combinations . The CERTs induced by clarithromycin, metronidazole, and tinidazole alone and in the combinations tested were concentration dependent, with no maximum response, indicating that the use of high doses may be preferable . The combinations with the highest concentrations induced synergistic effects and prevented regrowth . The use of tinidazole in combination with clarithromycin proved to give the longest CERTs, indicating that this is the most effective combination.

Prev Vet Med, 2002 Jun 25, 54(2), 141 - 56
Molecular epidemiology of feline bordetellosis in two animal shelters in California, USA; Foley JE et al.; "Kennel cough" in dogs in animal shelters is readily transmissible, reduces adoption rates, and commonly leads to the euthanasia of affected dogs . In cats, tracheobronchitis, conjunctivitis, and pneumonia have been associated with Bordetella bronchiseptica infection-but most cases of upper-respiratory infection (URI) probably are caused by herpesvirus and calicivirus, and many B . bronchiseptica culture-positive cats are clinically normal . Our prospective observational study was undertaken to document the contribution of B . bronchiseptica to disease in cats and dogs from two animal shelters undergoing outbreaks of canine kennel cough, to evaluate whether cross-species transmission might have occurred, and to determine if the presence of infected cats represented a risk to dogs . Clinically defined cases of kennel cough in dogs and URI in cats were investigated in two shelters by calculating clinical-disease incidence, alveolar-lavage cytological examination, bacterial and viral cultures, antibiotic-susceptibility testing, and molecular fingerprinting by pulsed-field gel electrophoresis.In a 40-cat and 40-dog "no-kill" shelter, the prevalences of culture positivity were 47% for B . bronchiseptica and 36% for calicivirus at the same time as two resident dogs demonstrated clinical cough . When no dogs had kennel cough 3 months later, 10% of cats were B . bronchiseptica-culture-positive and 63% calicivirus positive . In a large traditional shelter, the incidence of kennel cough in dogs increased over 12 weeks to a maximum of 19 cases/week/120 dogs, during which time the culture prevalence was 23% for B . bronchiseptica in dogs and 47% in cats . Three to 6 months before the kennel-cough epidemic, no dogs or cats were B . bronchiseptica positive . Very little genetic variability was detected in isolates from these shelters; all isolates except one corresponded to a single strain type which was identical to the pattern in a vaccine used in these shelters . Isolates from other cats, a horse, a llama, and a sea otter were genetically distinct from the shelter isolates . There was widespread resistance to cephalosporins and ampicillin, but low or no resistance to amoxicillin/clavulanate, trimethoprim-sulfamethoxazole, tetracycline, and enrofloxacin . Greater percent resistance was observed in the traditional shelter than in the no-kill shelter and feline isolates were more likely to be resistant than canine isolates.

Int J Tuberc Lung Dis, 2002 Jun, 6(6), 485 - 91
Tuberculosis transmission and the impact of intervention on the incidence of infection; Pitman R et al.; SETTING: England and Wales . OBJECTIVE: To quantify the relative contribution of vaccination, chemotherapy and preventive therapy to the reduction in tuberculosis incidence in England and Wales between 1953 and 1990 . DESIGN: A compartmental model of tuberculosis transmission was fitted to notification data between 1913 and 1939 to estimate pre-vaccination parameters . Best-fit estimates of the rates of chemotherapy and preventive therapy were derived by fitting the model to notification data between 1953 and 1990 . Published vaccination rates were used . MAIN OUTCOME MEASURE: Number of cases of pulmonary tuberculosis averted . RESULTS: The numbers of respiratory tuberculosis cases averted between 1953 and 1990 by the use of preventive therapy, vaccination and chemotherapy were 288318, 57085 and 206996, respectively . CONCLUSIONS: Of those interventions considered, preventive therapy has the greatest impact on transmission . The duration of infectiousness is long, with an onset that is likely to pre-date sputum positivity.

Int J Hyg Environ Health, 2002 May, 205(4), 257 - 68
The pathogenetic significance of intestinal Candida colonization--a systematic review from an interdisciplinary and environmental medical point of view; Lacour M et al.; The etiological significance of intestinal Candida colonization continues to be controversial . This is a systematic review to determine the pathogenetic significance of intestinal Candida colonization . The search was essentially performed from 1990 to 12/7/2000 in Medline and the Cochrane-Library . The data source was restricted to articles in English and German . Selection criteria covered the topics "Epidemiology", "Infectious Diseases", "Candida-Syndrome" and "Therapy" and were essentially confined to in-vivo examination of immunocompetent adults . Two reviewers extracted independently data using predefined criteria . In total, 96 citations that proved suitable for use in the systematic review were found . Depending on the localization in the gastrointestinal tract, the recovery technique employed, and transport times, Candida colonization is frequently detected in healthy, immunocompetent adults (prevalence: 4-88%) . None of the studies available so far furnish any evidence that nutritional factors, food additives, pollutants, anti-ovulants, other types of medication or diabetes mellitus might be predisposing factors for intestinal Candida colonization . However, therapeutic studies point to the possibility of Candida playing a role in antibiotic-associated diarrhea . On the other hand, antibiotics seem to favor bacterial dysbiosis, and this, like the direct side effects of drugs, offers a more plausible explanation for diarrhea or gastrointestinal symptoms . The role of intestinal colonization by Candida in Candida-associated vulvovaginitis and IgE-mediated disorders remains contradictory . Nevertheless, neither epidemiological nor therapeutic studies provide evidence for the existence of the so-called "Candida-syndrome" or "Candida-hypersensitivity-syndrome" . At present, there are no proven treatment indications for antifungal "bowel decontamination".

Biofizika, 2002 May-Jun, 47(3), 459 - 66
{Thermodynamic analysis of interaction of mitoxantrone with deoxytetranucleotide 5'-d(TpGpCpA) in the water solution based on 1H-NMR spectrophotometry}; Veselkov AN et al.; The complex formation of the antibiotic mitoxantrone (novantrone) with the deoxytetranucleotide 5'-d(TpGpCpA) in an aqueous salt solution was studied by one- and two-dimensional (2D-TOSCY and 2D-NOESY) 1H NMR spectroscopy (500 MHz) . Concentration and temperature dependence of proton chemical shifts of molecules were measured . On the basis of these data, the equilibrium constants of the reaction, the relative content of various complexes as a function of concentration and temperature, the limiting values of chemical shifts of novantrone in complexes, and the thermodynamic parameters delta H and delta S of complex formation of molecules were calculated . It was concluded that the attachment sites for novantrone are pyrimidine-purine nucleotide sequences, sites d(TG) and d(CA) of the tetranucleotide duplex . The analysis of the thermodynamic parameters of the complex formation suggests that intermolecular hydrogen bonds and electrostatic interactions of the aminoalkyl chains of novantrone with the duplex d(TpGpCpA)2 play an important role in the stabilization of complexes 1:2 and 2:2 . The results were compared with those obtained earlier for typical intercalators of ethidium bromide and daunomycin under identical experimental conditions.

Biofizika, 2002 May-Jun, 47(3), 444 - 8
{Effect of a substituent origin in actinocin amides on their binding to DNA}; Moroshkina EB et al.; The results of studies on the structure of complexes of DNA with compounds based on the actinocin chromophore, a center of binding of the antitumor antibiotic actinomycin D to DNA, were analyzed . In positions 1 and 9 of the chromophore of these compounds, pentapeptide lact ones of actinomycin D are replaced by groups of various origin . By using spectral, optical, and hydrodynamic methods a model of binding to DNA for each compound was constructed, and some regularities of complex formation depending on the structure of actinocin substituents and the amount of ligands in the complex were revealed.

J Arthroplasty, 2002 Jun, 17(4 Suppl 1), 98 - 101
Managing the infected knee: as good as it gets; Hanssen AD; The clinical presentation is a useful guide for selecting the treatment of an infected total knee arthroplasty . Prosthesis retention is indicated in patients with infections that occur within 30 days after arthroplasty and in patients with well-functioning prostheses who develop an acute late hematogenous infection . Debridement attempts should be open and not arthroscopic . When prosthesis removal is required, the preferred approach is a delayed reconstructive technique, the 2-staged reimplantation, rather than a direct-exchange procedure . The use of block spacers or mobile articulating devices to deliver high-dose local antibiotics is recommended between implant removal and delayed revision surgery . The use of antibiotic-loaded acrylic cement for cemented prostheses or antibiotic-soaked bone-graft with cementless prostheses is helpful in the overall cure rate of infection .

J Appl Microbiol, 2002, 93(1), 36 - 45
Comparison of genotypic and phenotypic techniques for assessing the variability of the fungus Epicoccum nigrum; Arenal F et al.; AIMS: The diversity within a collection of worldwide isolates of Epicoccum nigrum has been studied using several phenotypic approaches . In addition, the abilities of phenotypic and genotypic techniques for the differentiation of a set of isolates are compared . METHODS AND RESULTS: The methodology used include the study of isozymes (acetyl esterase and alkaline phosphatase), HPLC profile of metabolites and antibiotic activities against a panel of bacteria, yeasts and filamentous fungi, and cytotoxicity against three mammalian cell lines . Two procedures for assessing the relationships within a collection of isolates, using a combination of the techniques, were evaluated, comparing the advantages and disadvantages of each method . CONCLUSIONS: The results showed that each individual technique allows differentiation of the isolates studied to some degree and that the information provided by each technique could be considered as complementary . Genotypic techniques were more powerful than the phenotypic ones to discriminate among the strains . SIGNIFICANCE AND IMPACT OF THE STUDY: This work evaluates the predictive value of several phenotypic techniques on a collection of fungal isolates, and compares the results obtained with genotypic techniques performed on the same strains.

Emerg Med Serv . 2002 May;31(5):34.
Infections in the elderly: Part 3; Thurlow KL; The number of elderly individuals is rapidly growing . As a result, more emergency transports will involve the care of an elderly patient . Distinguishing the cause of symptoms can be difficult for healthcare professionals, including emergency personnel . Clinical symptoms of infection may be absent, or not as obvious as with a younger individual . The aging process of the immune system results in the inability to fight off many infections . Transport of patients with antibiotic-resistant organisms has caused many challenges for emergency care personnel surrounding infection control practices.

Pharm Dev Technol, 2002 May, 7(2), 235 - 48
Modifying the release of gentamicin from microparticles using a PLGA blend; Friess W et al.; Carrier systems for local gentamicin (GS) treatment based on collagen sponges and polymethylmethacrylate beads show pharmacokinetic disadvantages in their GS-release profiles . Therefore, poly(lactic-co-glycolic acid) (PLGA) microparticles were devised . None of the five poly(alpha-hydroxy acid)s tested resulted in the desired antibiotic release over approximately one week . However, preparing microparticles from a 50/50 blend of Resomer RG 502H, an uncapped variety, and Resomer RG 503, an endcapped polymer, yielded the targeted liberation profile . The mechanism of GS release was investigated by analyzing water uptake and polymer molecular weight . Release of GS from RG 502H particles occurred instantaneously and coincided with substantial water penetration . Particles prepared from RG 503 started out at a higher molecular weight and since the endcapped polymer takes up less water, the decrease in molecular weight was delayed . The threshold of collapse was reached after two weeks, which coincided with water penetration and GS release . For the 50/50 RG 502H/RG 503 blend, this process was delayed for two to three days . Hydrolysis occurred at the same rate as for RG 502H due to the high water content as a consequence of the uncapped polymer fraction and renders GS release over one week with release limited to 30% in the first two days due to the endcapped polymer fraction of higher molecular weight . Thus, the mixture of endcapped and uncapped Resome exhibits a new quality for adjusting drug release from poly(alpha-hydroxy acid)s.

Med J Aust, 2002 Jun 17, 176(12), 609 - 15
7: Soft tissue, bone and joint infections; Gottlieb T et al.; Soft tissue infections are common and usually respond rapidly to oral antibiotics; if empirical therapy fails then exposure to unusual organisms should be considered . Septic arthritis requires early recognition, identification of the infecting pathogen and urgent joint washout to prevent irreversible cartilage and bone destruction . Prosthetic joint infection is uncommon but has high morbidity; the best outcomes are achieved with removal of the prosthesis and replacement after at least six weeks of antibiotic therapy . Osteomyelitis often complicates diabetic foot infection with ulceration and is rarely cured by antibiotics alone; early surgical intervention achieves the best outcome.

J Clin Epidemiol, 2002 Jun, 55(6), 619 - 26
Standardized retrieval of side effects data for meta-analysis of safety outcomes . A feasibility study in acute sinusitis; Ioannidis JP et al.; Accurate and complete safety data are indispensable for the proper evaluation of the benefit-to-harm ratio of medical interventions . We evaluated whether a systematic review and meta-analysis of standardized safety data is feasible by requesting information on side effects directly from the investigators of all 38 antibiotic trials on acute sinusitis published in the last decade . We requested standardized information on gastrointestinal toxicity outcomes, including hospitalizations, discontinuations, and days with nausea/vomiting, diarrhea, or both . Responses were received only for 16 trials (42%), and safety data were contributed only for 9 trials (24%) . In some trials, safety data had not been collected, had been lost, or had been transferred to other companies . The odds of data retrieval was higher in general medical journals (P =.024) and independently improved with an increase in sample size (P =.064) . The available information suggested side effects may equal or exceed in severity the marginal treatment benefits . Interpretation of safety data was further complicated by heterogeneity or lack of information of use of concomitant drugs, mode of collection of safety information, use of blinding, and other study design parameters . Availability of standardized information for performing meta-analysis of safety data may be limited . Standardized reporting, prospective collection, and long-term availability of safety information should be improved.

J Pharm Biomed Anal, 2002 Jun 20, 29(1-2), 229 - 38
Spectrofluorometric determination of naproxen in tablets; Damiani P et al.; A rapid, selective, sensitive and simple fluorescence method was developed for the direct determination of naproxen in tablets . The tablets were triturated, dissolved in either NH(3) or NaOH solution, sonicated, filtered and then direct fluorescence emission was read at 353 nm (exciting at 271 nm) . In order to validate the method the results were compared with those obtained by the USP XXIV NF 19 Pharmacopeia reference method (high performance liquid chromatography) . The slope, intercept and variances which are associated with the regression coefficient calculated with bivariate least square (BLS) regression indicate that both methods are statistically comparable . The recoveries were excellent, except in tablets containing the antibiotic tetracycline . In this latter case a correction procedure is necessary.

Arch Biochem Biophys, 2002 Jul 1, 403(1), 1 - 15
Thermodynamics of drug-DNA interactions; Haq I; Many anticancer, antibiotic, and antiviral drugs exert their primary biological effects by reversibly interacting with nucleic acids . Therefore, these biomolecules represent a major target in drug development strategies designed to produce next generation therapeutics for diseases such as cancer . In order to improve the clinical efficacy of existing drugs and also to design new ones it is necessary to understand the molecular basis of drug-DNA interactions in structural, thermodynamic, and kinetic detail . The past decade has witnessed an increase in the number of rigorous biophysical studies of drug-DNA systems and considerable knowledge has been gained in the energetics of these binding reactions . This is, in part, due to the increased availability of high-sensitivity calorimetric techniques, which have allowed the thermodynamics of drug-DNA interactions to be probed directly and accurately . The focus of this article is to review thermodynamic approaches to examining drug-DNA recognition . Specifically, an overview of a recently developed method of analysis that dissects the binding free energy of these reactions into five component terms is presented . The results of applying this analysis to the DNA binding interactions of both minor groove drugs and intercalators are discussed . The solvent water plays a key role in nucleic acid structure and consequently in the binding of ligands to these biomolecules . Any rational approach to DNA-targeted drug design requires an understanding of how water participates in recognition and binding events . Recent studies examining hydration changes that accompany DNA binding by intercalators will be reviewed . Finally some aspects of cooperativity in drug-DNA interactions are described and the importance of considering cooperative effects when examining these reactions is highlighted.

Surg Today, 2002, 32(5), 443 - 5
Psoas abscess as a complication of pyogenic sacroiliitis: report of a case; Gorgulu S et al.; A psoas abscess is, either primary or secondary, a rare entity for a general surgeon . Images by ultrasonography and computed tomography (CT) can help a general surgeon to make an accurate diagnosis when encountering the patient complaining of unilateral lower abdominal deep pain with fever . A case of pyogenic abscess of the psoas muscle as a result of sacroiliitis in a 22-year-old man is reported herein . The abdominal CT and magnetic resonance imaging scans demonstrated a large multilocular abscess extending along the iliopsoas muscle, and erosion and a widening of the left sacroiliac joint . The abscess was drained with an open surgical approach and the patient responded well to antibiotic therapy . Aggressive surgical and medical treatment is necessary in patients with psoas abscess to prevent complications.

Mediators Inflamm, 2002 Apr, 11(2), 95 - 8
Levels of soluble ICAM-1 in premature and full-term neonates with infection; Apostolou M et al.; BACKGROUND: Infection in the neonatal period is an extremely serious condition and diagnosis is difficult . C-reactive protein (CRP) is widely used as a marker of infection; however, its usefulness is limited in the early phase . The role of soluble intracellular adhesion molecule-1 (sICAM-1), an adhesion molecule, has been examined in recent studies as an early marker of neonatal infection with controversial results . AIM: Assessment of sICAM-1 concentrations and correlation with CRP, which is the currently used marker of infection, in order to use sICAM as an early diagnostic tool in neonates suspected for infection METHODS: Blood samples and blood cultures were obtained from two groups of pre-term and full-term neonates with clinical suspicion of infection prior to the initiation of antibiotics . The sICAM-1 and CRP values were compared with the corresponding noninfected ones (n = 10 each) . RESULTS: The sICAM-1 levels were found increased in the group of both premature and term neonates with infection compared with the corresponding healthy ones (P < 0.0001) . Prematurity combined with infection resulted in excessive increase of the levels of sICAM-1 in comparison with full-term infected newborns (p < 0.001) . CRP values were normal in all samples except one in both full-term and premature infected neonates on day 1 of clinically suspected infection . Serial detection of CRP values on days 2 and 4 of infection revealed a pattern according to which CRP values in premature neonates continued rising, while in the group of full terms these values, after rising on the second day, lowered on day 4 . CONCLUSIONS: Increased sICAM-1 levels can be detected early in both full-term and premature neonates with sepsis while CRP levels are within normal range at the same time . Assessment of sICAM-1 concentrations may be used as a diagnostic tool in neonates suspected for infection, resulting in earlier initiation of antibiotic therapy and therefore improving their outcome.

Vnitr Lek, 2002 Apr, 48(4), 285 - 9
{Treatment of diabetic neuropathic defect at the surgery department and at the center for diabetic foot care}; Rusavy Z et al.; The aim of the study was to evaluate the treatment of neuropathic diabetic ulcer at the surgery department and the treatment at the diabetic foot centre at dismissal time and 3 months after the dismissal . METHODS: For assessment of treatment success parameters of glucose control were used (average of daily blood glucose values, glycosylated haemoglobin--HbA1C and glycosylated protein), healing of ulcers (Wagner classification), hospitalisation time and number of amputations . 22 diabetic patients at the centre and 17 patients at the surgical department were observed in this investigation . There was no difference between the groups as for the age, glucose control (HbA1C), and severity of diabetic ulcers (Wagner 3-4) . Local and antibiotic therapies were the same ones . Results as median and difference 75th and 25th percentile were evaluated by Wilcoxon test for paired data within the groups and by Man-Whitney test between both of the groups . RESULTS: In the both group the diabetic control and ulcer healing were significantly improved during hospitalisation period, 3 months after discharge deteriorate diabetic control and ulcer healing stagnated, however, only in the group treated at the surgical department . The hospitalisation time was significantly longer in the surgical group in comparison with the centre group {median 52 days (35)} vs . {median 31 days (38)}, p < 0.01 . Amount of transmetatarsal and higher amputations was lower at the foot centre in comparison with the surgical group (1 vs . 7) . Statistical evaluation was not used for low amount of amputations . CONCLUSION: Team approach at the centre of diabetic foot is effective in the treatment of diabetic foot ulcers, significantly shortened the hospital stay, probably decrease amount of amputations . Three months after discharge the diabetic control and ulcer healing were significantly better in patients treated at the diabetic foot centre.

Pharm World Sci, 2002 Apr, 24(2), 61 - 6
An evaluation of quinolone prescribing in a group of acute hospitals: development of an objective measure of usage; Curtis C et al.; OBJECTIVES: To develop an objective measure to enable hospital Trusts to compare their use of antibiotics . DESIGN: Self-completion, postal questionnaire with telephone follow up . SAMPLE: 4 hospital trusts in the English Midlands . RESULTS: The survey showed that it was possible to collect data concerning the number of Defined Daily Doses (DDD's) of quinolone antibiotic dispensed per Finished Consultant Episode (FCE) in each Trust . In the 4 trusts studied the mean DDD/FCE was 0.197 (range 0.117 to 0.258) . This indicates that based on a typical course length of 5 days, 3.9% of patient episodes resulted in the prescription of a quinolone antibiotic . Antibiotic prescribing control measures in each Trust were found to be comparable . CONCLUSION: The measure will enable Trusts to objectively compare their usage of quinolone antibiotics and use this information to carry out clinical audit should differences be recorded . This is likely to be applicable to other groups of antibiotics.

Bull Hist Med, 2002 Summer, 76(2), 271 - 98
Rooming-in: redesigning hospitals and motherhood in cold war America; Temkin E; Rooming-in, a model of maternity care that placed newborns in their mothers' rooms instead of central nurseries, appeared in American hospitals in the early 1940s, advocated by physicians and mothers as an antidote to the emotional sterility of the modern maternity ward . It has been cited as a successful illustration of health-care reform, in which practitioners and patients redesigned postpartum care to make it more fulfilling . However, factors other than visionary leadership contributed to the establishment and popularity of rooming-in . First, wartime changes in the medical care of postpartum patients, including antibiotic therapy and early ambulation, paved the way for a system in which mothers played an active role . Second, rooming-in effectively solved two hospital crises: a nursing shortage, and an epidemic of infections in newborn nurseries . Finally, it achieved notoriety far beyond its actual prevalence because it resonated with trends in mass culture: a wariness of technology, interest in the causes and prevention of neurosis, and the "feminine mystique." This article suggests that changes in health care depend less on reasoned planning than on coincidental events inside and outside the hospital.

J Chromatogr A, 2002 Apr 19, 954(1-2), 33 - 40
Initial study of using a laminar fluid diffusion interface for sample preparation in high-performance liquid chromatography; Jandik P et al.; This report describes a new microfluidic device called the H Filter for sample preparation prior to HPLC . The H Filters make possible a diffusional transfer of an analyte from a sample stream into a stream of a "receiver" fluid . Existing mathematical models can be used for optimizing experimental conditions . The authors have selected the extraction of the antibiotic cephradine from blood to demonstrate the utility of the new device . The extracts of blood samples spiked with cephradine levels between 0.2 and 100 microg/ml were analyzed using a C8 reversed-phase column and UV detection at 260 nm . The HPLC results were in good agreement with theory . The recovery of 32.2+/-2.8% was uniform over the entire range of cephradine concentrations . The new method completely avoids the use of centrifuges, that is otherwise typical for most current methodologies for the preparation of blood samples prior to HPLC analysis.

J Mol Cell Cardiol, 2002 May, 34(5), 493 - 507
Cardiomyocyte resistance to doxorubicin mediated by A(3) adenosine receptor; Shneyvays V et al.; Recently, we reported that the activation of A(3) adenosine receptor (A(3)R) in newborn cultured cardiomyocytes by highly selective agonist Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) induces protection against the anthracycline antibiotic doxorubicin (DOX) cardiotoxicity . The present study was undertaken to further characterize the cardioprotective action of A(3)R activation by revealing the structural changes in cardiomyocytes elicited upon exposure to DOX . Morphological observations (ultrastructural and immunocytochemical) indicate that after DOX treatment, the cardiomyocytes undergo destructive alterations, and protective action of A(3)R is not connected with its anti-apoptotic activity . A(3)R activation appeared to prevent destructive alterations of cardiomyocyte mitochondria and dissipation of mitochondrial membrane potential . In DOX-treated cardiomyocytes, appearance of disorganized desmin and contractile filaments was related to detrimental alterations in the mitochondrial structure, in particular their position and transmembrane potential . In intact cardiomyocytes, diazoxide, a selective mitochondrial K(ATP) channel opener, induced an increase in ATP synthesis within 15 min of application . Similar effect was obtained by activation of adenosine A(1)R . However, A(3)R agonist Cl-IB-MECA did not affect ATP synthesis . Neither A(1)R agonist CCPA (2-chloro-N(6)-cyclopentyladenosine) nor diazoxide protected cardiomyocytes from the detrimental effects of DOX . Thus, the opening of mitochondrial K(ATP) channels does not seem to be effective during the slow development of anthracycline cytotoxicity . Our results indicate that DOX increases the activity of lysosomes, which may contribute to cell injury in an "oncotic" manner and also demonstrate the proinflammatory potency of the drug . Furthermore, the decreased acidification of cytoplasm upon activation of A(3)R may attenuate the ongoing inflammatory response . The present study identifies a novel role for A(3)R selective agonist Cl-IB-MECA and suggests its importance in regulating cardiac cellular function .

Curr Opin Pulm Med, 2002 Jul, 8(4), 327 - 33
Postpneumonectomy empyema; Abbas Ael-S et al.; Empyema is a serious complication after pneumonectomy . It is often associated with a bronchopleural fistula . Several risk factors have been associated with an increased incidence of these two challenging complications . Therapy aims at simultaneously treating the infected pleural space and the fistula . The authors describe their favorite methods which include repeated open debridements of the pleural space, primary closure of the fistula, and covering of the bronchial stump using intrathoracic transposition of extrathoracic skeletal muscle followed by delayed closure of the chest wall after instillation of an antibiotic solution (Clagett and modified Clagett procedures) . The goals of treatment remain a healthy patient with a healed chest wall and no evidence of drainage or infection . Excellent results can be obtained in more than 80% of patients . Failure is often associated with a persistent or recurrent bronchopleural fistula.

Biochem Biophys Res Commun, 2002 Apr 26, 293(1), 207 - 12
Alloxan is an inhibitor of the enzyme O-linked N-acetylglucosamine transferase; Konrad RJ et al.; We have previously shown that diabetogenic antibiotic streptozotocin (STZ), an analog of N-acetylglucosamine (GlcNAc), inhibits the enzyme O-GlcNAc-selective N-acetyl-beta-d-glucosaminidase (O-GlcNAcase) which is responsible for the removal of O-GlcNAc from proteins . Alloxan, another beta-cell toxin is a uracil analog . Since the O-GlcNAc transferase (OGT) uses UDP-GlcNAc as a substrate, we investigated whether alloxan might interfere with the process of protein O-glycosylation by blocking OGT, a very abundant enzyme in beta-cells . In isolated pancreatic islets, alloxan almost completely blocked both glucosamine-induced and STZ-induced protein O-GlcNAcylation, suggesting that alloxan indeed was inhibiting (OGT) . In order to show definitively that alloxan was inhibiting OGT activity, recombinant OGT was incubated with 0-10 mM alloxan, and OGT activity was measured directly by quantitating UDP-{(3)H}-GlcNAc incorporation into the recombinant protein substrate, nucleoporin p62 . Under these conditions, OGT activity was completely inhibited by 1 mM alloxan with half-maximal inhibition achieved at a concentration of 0.1 mM alloxan . Together, these data demonstrate that alloxan is an inhibitor of OGT, and as such, is the first OGT inhibitor described.

J Parasitol, 2002 Feb, 88(1), 209 - 11
Anticryptosporidial prophylactic efficacy of enrofloxacin and paromomycin in chickens; Sreter T et al.; Two battery tests were conducted to study the anticryptosporidial prophylactic efficacy of the 2 commercially available antibiotics, enrofloxacin and paromomycin . The efficacy of enrofloxacin was 52% at the recommended level, which could not be increased, using twice the recommended dose . At the recommended levels, paromomycin reduced the oocyst output of birds by 67-82%, showing the highest efficacy of all drugs tested against avian cryptosporidiosis thus far . Moreover, the patent period was shortened by 12-23% . The body weight gain of paromomycin-treated chickens was almost identical with that of uninfected, untreated control birds irrespective of dosage, indicating the lack of toxicity . Although paromomycin is not registered for use in birds, in combination with sanitary procedures and disinfection, it may help in the control of cryptosporidiosis in some bird facilities.

Trans Am Clin Climatol Assoc, 2002, 113, 42 - 53; discussion 53-5
Recognizing the real threat of biological terror; Wenzel RP; Weapons of mass destruction can be used to harm and terrorize populations . Such weapons include those with chemical, nuclear or biological properties . Obviously computer viruses can add additional barriers to a quick response . The most effective, least costly and greatest threats are biologicals . Biological terror is not new, and biological weapons have been used for centuries . However, as a result of modern technology, the risks are greater now and the outcomes more terrible . Today they include live pathogens, various toxins, and theoretically "bioregulators"--biochemicals affecting cell signaling . Altered cell signaling could be used to induce apoptosis-cell death, or a heightened outpouring of cytokines mimicking overwhelming sepsis, or even an intracellular, biochemical "strike" causing cellular paralysis . Biological weaponeers now have the frightening ability to alter the genetic makeup of pathogens, rendering them resistant not only to available antibiotic therapy but also to currently effective vaccines . In dark corners of some fringe groups, bioweaponeers are searching for the capability of designing pathogens that target specific races, by virtue of discriminating ligands (1) . The resulting morbidity and mortality from use of any biological weapons will be accompanied by chaos, governmental and social instability, panic, an extraordinary utilization of available resources, and an ongoing epidemic of sleepless nights (2,3) . Herein I will review some of the issues and some of the currently available biological weapons . The major goal is to highlight the clinical presentations of patients with infections that could be used as biological weapons.

Pol Merkuriusz Lek, 2002 Mar, 12(69), 241 - 4
{Fungal allergy . Part I}; Niedoszytko M et al.; Fungal spores are one of the main groups of allergens . They are present in our environment all year long . The concentration of the spores in July and August is 100-1000 higher than pollens . In contrast with the pollens there is a correlation between the spore count and higher risk of medication use, nocturnal asthma attacks, and hospitalization rates . We have presented the clinical classification of fungi, and characterized main indoor and outdoor allergens . The fungi play also an important role in the sick building syndrome . Fungal allergens are not only aeroallergens, they may also get into our body with food . They may also develop contact reactions . Antibiotic allergy is regarded as one of the classic allergic reactions caused by fungi . The id reactions are caused by the fungi from far infection focuses.

An Otorrinolaringol Ibero Am, 2002, 29(2), 187 - 93
{Thrombophlebitis of the lateral sinuses . A difficult diagnostic case for nine otorhinolaryngologists}; Redondo Ventura F et al.; Since the advent of antibiotic era lateral sinus thrombophlebitis has become an scarce complication in otology . The clinical picture can present under several aspects, specially if given a course of antibiotics previously, which complicates the diagnose . We report a case recently treated and compare ours with the classic symptomatology quoted in the literature.

Biotechnol Prog, 2002 May-Jun, 18(3), 451 - 7
Clavulanic acid degradation in Streptomyces clavuligerus fed-batch cultivations; Roubos JA et al.; Clavulanic acid (CA) is an important antibiotic that is produced by Streptomyces clavuligerus . CA is unstable and product degradation has turned out to have a major impact on product titers in fed-batch cultivations . Three different types of experiments have been used to elucidate CA degradation under fed-batch cultivation conditions . First, the influence of individual medium compounds was examined . Second, degradation was monitored during the exponential growth phase in batch cultivations . Third, CA degradation was studied in the supernatant of samples taken during a fed-batch . In addition, data from six fed-batch cultivations were studied to derive information about CA degradation during the production phase . These cultivations were based on a mineral medium, containing glycerol, glutamate, ammonium, and phosphate as the main nutrients . The ammonium concentration had a large influence on the degradation rate constant . In addition, either changes in the substrate availability or high concentrations of ammonium or glycerol cause a major increase in the degradation rate constant . Finally, a linear and a fuzzy logic model were made to predict CA degradation rates in these fed-batches.

Mol Genet Metab, 2002 Apr, 75(4), 325 - 34
Cholesterol storage defect in RSH/Smith-Lemli-Opitz syndrome fibroblasts; Wassif CA et al.; The RSH/Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental retardation syndrome caused by an inborn error of cholesterol synthesis . Mutations in the 3beta-hydroxysteroid Delta(7)-reductase gene result in impaired enzymatic reduction of 7-dehydrocholesterol (7-DHC) to cholesterol . Cells obtain cholesterol by either de novo synthesis or from exogenous sources by the binding and uptake of low density lipoprotein (LDL) particles . Because de novo synthesis of cholesterol is impaired in SLOS, current investigational therapy for SLOS consists of dietary cholesterol supplementation . However, the potential effects of elevated intracellular levels of 7-DHC on intracellular LDL metabolism have not been described . We now report that in addition to the primary defect in de novo cholesterol synthesis, SLOS fibroblasts have a secondary defect of LDL cholesterol metabolism . Staining of fibroblasts with filipin, a fluorescent polyene antibiotic which binds unesterified sterols, shows that SLOS fibroblasts accumulate unesterified sterols . Further studies show that this increased filipin staining was due to an abnormal accumulation of LDL derived cholesterol rather than due to storage of endogenously synthesized 7-dehydrocholesterol (7-DHC) . We have also found that SLOS fibroblasts failed to degrade LDL at a normal rate, and examination of SLOS fibroblasts by electron microscopy demonstrated the formation of lysosomal inclusions similar to that seen in Niemann-Pick type C (NPC) cells . We propose that 7-DHC may directly or indirectly inhibit the function of the NPC protein through its sterol-sensing domain (SSD), and that 7-DHC may perturb the function of other SSD containing proteins in SLOS.

Biochem Biophys Res Commun, 2002 May 10, 293(3), 993 - 9
Subgenomic replicon derived from a cell line infected with the hepatitis C virus; Kishine H et al.; Recently, cell culture systems have been established, where a hepatitis C virus (HCV) subgenomic replicon was efficiently replicated and maintained for a long period . To see whether a HCV sequence derived from HCV-infected cultured cell sequence can be used for the construction of a functional replicon, a HCV subgenomic RNA carrying a neomycin-resistant gene was constructed using the HCV genome RNA obtained from cultured cells infected with HCV . After transfection, G418-resistant Huh-7 cells were selected and subcloned . Finally, the production of HCV proteins and de novo synthesis of subgenomic RNA were confirmed in the selected cell clone, indicating that this subgenomic RNA replicated in cultured cells and functioned as a replicon . These results suggest that the HCV genome obtained from an in vitro HCV infection system with cultured cells can be used to develop a subgenomic replicon system with diverse HCV sequences . (c) 2002 Elsevier Science (USA).

Br J Gen Pract, 2002 Jun, 52(479), 491 - 5
The clinical diagnosis of acute purulent sinusitis in general practice--a review; Lindbaek M et al.; Acute sinusitis is a common illness in primary care . Studies have demonstrated the difficulty of making the differential diagnosis of acute purulent sinusitis based on clinical evaluations alone . This leads to a significant overuse of antibiotics, which in turn may contribute to increased bacterial resistance . In most cases, GPs have to base their differential diagnosis of sinusitis on clinical signs and symptoms and examination of the patient . The aim of this review is to assess which clinical signs and symptoms can predict an acute purulent sinusitis, compared with accepted reference standards . A review of the literature was performed by looking at articles related to the diagnoses of acute sinusitis in general practice . The following search criteria were used: unselected general practice population; objective reference standard; and logistic regression to evaluate symptoms and signs independently associated with the diagnosis . Four studies were identified for further analysis . The following symptoms and signs were associated with acute purulent sinusitis: purulent secretion as a symptom experienced by the patient or as a sign demonstrated in the nasal cavity by the doctor; pain in the teeth; pain at bending forward, and two phases in the illness history . An elevated erythrocyte sedimentation rate and increased C-reactive protein also contributed to the diagnosis . By use of the specified signs and symptoms the GP can increase the probability of correctly diagnosing an acute purulent sinusitis and reserve antibiotic prescription for these patients.

Acta Orthop Belg, 2002 Apr, 68(2), 150 - 6
Two-stage exchange of infected knee arthroplasty with an prosthesis-like interim cement spacer; Siebel T et al.; Two-stage revision in infected knee arthroplasty is standard practice . One problem during the interim period is soft tissue fibrosis . Attempts have been made to preserve leg length and ligament length by introducing spacers, usually made out of antibiotic-loaded bone cement . We present a new interim prosthesis, which is made intra-operatively out of polymethylmethacrylate (PMMA) . Antibiotic-loaded cement provides a therapeutic level of antibiotics in the periarticular soft tissue . We report the results in ten patients, who were treated with this prosthesis-like spacer and were prospectively studied . After an average follow-up of 13.5 months, there was no recurrent infection.

Magy Onkol, 2001, 45(5), 403 - 405
{The role of irinotecan in the treatment of advanced colorectal cancer}; Marazi L et al.; PURPOSE: The purpose of the study was the evaluation of efficacy and the side effects of irinotecan in treatment of advanced colorectal cancer . METHODS: The authors presented their experiences with irinotecan in the treatment of 10 patients suffering from advanced colorectal cancer . The dose of irinotecan was 350 mg/m(2) every 21 days . Seven out of ten patients have taken oral fluoroquinolon to investigate its effect on the incidence of febrile episodes in case of febrile neutropenia . Three out of ten patients did not receive any antibiotic . The authors have examined the efficacy and safety of the treatment . RESULTS: One complete remission was obtained . Authors describe the observed side effects and the administered supportive care against serious complications . DISCUSSION: Serious diarrhoea has not been found in case of these 10 patients . The diarrhoea caused by irinotecan can be stopped by loperamide . The authors give accounts of early and following results.

N Engl J Med, 2002 Jun 6, 346(23), 1792 - 8
Central nervous system infection in congenital syphilis; Michelow IC et al.; BACKGROUND: Identification of infants with Treponema pallidum infection of the central nervous system remains challenging . METHODS: We used rabbit-infectivity testing of the cerebrospinal fluid to detect T . pallidum infection of the central nervous system in infants born to mothers with syphilis . The results were compared with those of clinical, radiographic, and conventional laboratory evaluations; IgM immunoblotting of serum and cerebrospinal fluid; polymerase-chain-reaction (PCR) assay testing of serum or blood and cerebrospinal fluid; and rabbit-infectivity testing of serum or blood . RESULTS: Spirochetes were detected in the cerebrospinal fluid of 19 of 148 infants by rabbit-infectivity testing . Exposure of the infant to antibiotics before cerebrospinal fluid was obtained for rabbit-infectivity testing was associated with a negative test result (P=0.001) . Spirochetes were detected in the cerebrospinal fluid in 17 of 76 infants (22 percent) who had no prior antibiotic exposure . These 17 infants included 41 percent (16 of 39) of those with some abnormality on clinical, laboratory, or radiographic evaluation; 60 percent (15 of 25) of those with abnormal findings on physical examination that were consistent with congenital syphilis; and 41 percent (17 of 41) of those with a positive result on IgM immunoblotting or PCR testing of serum, blood, or cerebrospinal fluid, or a positive result on rabbit-infectivity testing of serum or blood . Only one infant who had normal findings on clinical evaluation had a positive cerebrospinal fluid rabbit-infectivity test . Overall, central nervous system infection was best predicted by IgM immunoblotting of serum or PCR assay of serum or blood . CONCLUSIONS: Most infants with T . pallidum infection of the central nervous system can be identified by physical examination, conventional laboratory tests, and radiographic studies . However, the identification of all such infants requires the use of additional tests, including IgM immunoblotting and PCR assay.

Int J Pediatr Otorhinolaryngol, 2002 Jun 17, 64(2), 89 - 95
Diagnostic certainty for acute otitis media; Rosenfeld RM; Our primary objective was to assess diagnostic accuracy for acute otitis media (AOM) relative to the criterion standard established by the United States Agency for Healthcare Research and Quality: middle-ear effusion (MEE) plus onset in the past 48 h of signs or symptoms of middle-ear inflammation . A secondary objective was to assess the potential reduction in antibiotic usage that could be achieved if clinicians managed AOM according to a consensus guideline developed by the New York Region Otitis Project (NYROP) . A convenience sample of primary care practitioners were surveyed after diagnosing AOM in 135 children aged 0.3-11.8 years (median 2.4 years) . Clinicians expressed high certainty for AOM diagnosis in 122/135 episodes (90%) . The prevalence of true AOM was 70% with a positive predictive value for high certainty of 76% . Of the 40 false-positive diagnoses, 35 did not have MEE and 5 did not have acute signs or symptoms . The relative risk for receiving an antibiotic was 1.50 times higher when clinicians expressed certainty (P=0.005), which produced 31/120 (26%) potentially unnecessary antibiotic prescriptions . Initial antibiotics would not have been prescribed for 29% of episodes using the NYROP guidelines . More judicious use of antibiotics may result if clinicians deferred initial therapy in children without definitive AOM, particularly when the presence of MEE is uncertain.

Bioelectrochemistry, 2002 Jul, 57(1), 1 - 7
Impedance analysis of ion transport through gramicidin channels in supported lipid bilayers; Vallejo AE et al.; Selectivity between monovalent cations and its sequence of conductivity in lipid bilayers doped with the antibiotic Gramicidin D (GD) were examined using EIS . Experiments were performed using lipid bilayers obtained from a lipid mixture of phosphatidylcholine and dimethyldioctadecylammonium chloride (DODAC) . Lipid bilayers were supported on gold surfaces modified with a mercapto-carboxylic acid . The bilayers were formed by chemisorption of this last species to form the first monolayer on gold and subsequent fusion of unilamellar vesicles to form an external bilayer attached by electrostatic interactions . A mathematical expression for the impedance of the membrane processes was derived . Some predictions of the presented model were checked after fitting the experimental results in various electrolyte compositions.

J Clin Pediatr Dent, 2001 Spring, 25(3), 237 - 9
An unusual form of Actinomycosis of the mandible with a resultant gross sequester in a 4-year-old child: a case report; Ogutcen-Toller M et al.; Mandibular osteomyelitis due to Actinomyces group is considered rare in the pediatric population . The initial complaint of the 4-year-old child described here was increased swelling of his cheek and pain . The patient was managed successfully by surgical treatment with antibiotic therapy.

Eur J Cardiothorac Surg, 2002 Jun, 21(6), 1061 - 72
Short- and long-term results of open heart surgery in patients with abdominal solid organ transplant; Ono M et al.; OBJECTIVES: Cardiac disease is a common cause of mortality and morbidity in patients with abdominal solid organ transplant . Improvement of the results of abdominal organ transplantation has contributed to an increasing pool of patients who require open heart surgery . We investigated short- and long-term results of open heart surgery in patients with functioning abdominal solid organ transplants . METHODS: We retrospectively examined 60 patients (52.5 years in average) undergoing coronary artery bypass grafting and/or valve surgery since July 1988 after abdominal organ transplantation . There were 22 females (37%) . They consisted of 46 kidney, nine kidney-pancreas and five liver recipients . Cardiac surgery was performed 68.9 months after transplantation . Preoperative serum creatinine level was 2.1 mg/dl, and 11 patients (18%) had creatinine level more than 3.0 mg/dl . Eleven patients (18%) were operated upon on non-elective basis . Twelve patients (20%) were not given stress-dose steroids postoperatively . RESULTS: Three patients died early after surgery (5.0%) . Twenty-six major complications were seen in 17 patients (28%), including deterioration of renal function in seven (three patients required temporary hemodialysis), three major infections, two bleeding complications, and two strokes . No graft loss was encountered . No differences were seen in mortality and morbidity between patients with or without stress-dose steroids . Multivariate analysis identified cardiopulmonary bypass time (P<0.05) as a risk factor for operative death, preoperative creatinine level (P<0.05), cardiopulmonary bypass time (P<0.05) and the amount of fresh frozen plasma used (P<0.05) for major complication, non-elective surgery (P<0.01) for deterioration of renal function . Thirteen patients died and five kidney allografts failed late after surgery . Three- and 5-year patient and graft survivals were 70.8 and 66.8, 84.5 and 84.5%, respectively . Multivariate regression analysis identified female gender (P<0.05), body mass index (P<0.001) and non-elective surgery (P<0.001) as risk factors for late death, and preoperative creatinine level (P<0.05) for late graft loss . CONCLUSIONS: Open heart surgery can be performed with acceptable short- and long-term results in patients with functioning abdominal transplants . Stress-dose steroid may be unnecessary in selected patients . Aggressive use of open heart surgery in this patient population to avoid non-elective surgery may further improve early and late surgical outcomes.

Plast Reconstr Surg, 2002 Jun, 109(7), 2231 - 7
First-line treatment of deep sternal infection by a plastic surgical approach: superior results compared with conventional cardiac surgical orthodoxy; Brandt C et al.; A majority of cardiac surgeons manage deep sternal infection with sternal wound debridement, rewiring, and closed drainage, with or without antibiotic saline tube irrigation (the traditional approach) . The authors' experience with the traditional approach was unsatisfactory; therefore, they undertook a radical change in management: an immediate plastic surgical approach . Hence, deep sternal infection was managed by immediate debridement followed by a bilateral pectoralis major myocutaneous advancement flap with greater omental transposition (PMOFR) . This is the first such study reporting the effect of this strategy on the rate of eradication of deep sternal infection, intensive care unit stay, total hospital length of stay, major complications, mortality, intermediate survival, and patient satisfaction, as compared with the traditional approach used by cardiac surgeons at the authors' institution.All patients who developed a deep sternal infection from 1993 through 1998 at a tertiary teaching hospital were included . In the PMOFR group (nine patients), after a diagnosis of clinical sternal wound infection, debridement was performed immediately, either if sternal dehiscence occurred or in the absence of clinical dehiscence, if the patient or the sternotomy wound did not clinically improve with medical therapy within 48 hours from suspected diagnosis . Open irrigation and packing for 2 to 4 days was followed by treatment with a PMOFR . In the group treated using the traditional approach (12 patients), no predetermined plan was present . Thus, at the cardiac surgeon's discretion, wound debridement was undertaken, followed by closed drainage (three patients), closed tube irrigation (six patients), and open granulation with delayed plastic surgery (three patients).The incidence of major complications (PMOFR, 22 percent; traditional approach, 92 percent; p = 0.001), intensive care unit readmission (PMOFR, 0 percent; traditional approach, 58 percent; p = 0.005), total hospital length of stay (PMOFR, 32 days; traditional approach, 79 days; p = 0.001), reoperation rates (PMOFR, 0 percent; traditional approach, 100 percent; p = 0.001) and in-hospital 30-day mortality rate (PMOFR, 0 percent; traditional approach, 33 percent; p = 0.05) were superior in the PMOFR group . At a mean follow-up of 2 years, freedom from recurrence of the infection (PMOFR, 100 percent; traditional approach, 11.5 percent; p = 0.005) and overall survival rate (PMOFR, 100 percent; traditional approach, 50 percent; p = 0.005) were also superior with PMOFR . A majority of patients in the PMOFR group (90 percent) had no functional or cosmetic complaints secondary to the procedure.A predetermined plan of immediate debridement followed by treatment with PMOFR rapidly, reliably, and effectively eradicated deep sternal infection . This translated to reduced length of stay and need for additional surgery, improved survival, and excellent intermediate freedom from deep sternal infection, with minimal patient dissatisfaction . The traditional approach to managing deep sternal infection was thus abandoned.

J Cell Sci, 2002 Jun 15, 115(Pt 12), 2569 - 80
Rho-dependent and -independent activation mechanisms of ezrin/radixin/moesin proteins: an essential role for polyphosphoinositides in vivo; Yonemura S et al.; Ezrin/radixin/moesin (ERM) proteins crosslink actin filaments to plasma membranes and are involved in the organization of the cortical cytoskeleton, especially in the formation of microvilli . ERM proteins are reported to be activated as crosslinkers in a Rho-dependent manner and are stabilized when phosphorylated at their C-terminal threonine residue to create C-terminal threonine-phosphorylated ERM proteins (CPERMs) . Using a CPERM-specific mAb, we have shown, in vivo, that treatment with C3 transferase (a Rho inactivator) or staurosporine (a protein kinase inhibitor) leads to the dephosphorylation of CPERMs, the translocation of ERM proteins from plasma membranes to the cytoplasm and microvillar breakdown . We further elucidated that ERM protein activation does not require C-terminal phosphorylation in A431 cells stimulated with epidermal growth factor . In certain types of kidney-derived cells such as MDCK cells, however, ERM proteins appear to be activated in the absence of Rho activation and remain active without C-terminal phosphorylation . Interestingly, microinjection of an aminoglycoside antibiotic, neomycin, which binds to polyphosphoinositides, such as phosphatidylinositol (4,5)-bisphosphate {PtdIns(4,5)P(2)}, affected the activation of ERM proteins regardless of cell type . These findings not only indicate the existence of a Rho-independent activation mechanism of ERM proteins but also suggest that both Rho-dependent and -independent activation of ERM proteins require a local elevation of PtdIns(4,5)P(2) concentration in vivo.

Int J Infect Dis, 2002 Mar, 6(1), 60 - 5
A pilot study of treatment of Buruli ulcer with rifampin and dapsone; Espey DK et al.; OBJECTIVE: Buruli ulcer disease (BU), caused by Mycobacterium ulcerans, is endemic in many regions of Africa and causes substantial physical disability . Surgical resection, currently the mainstay of clinical management of BU, is impractical in many endemic areas . Therefore, the study was undertaken to evaluate an antibiotic regimen for medical management of BU . METHODS: A randomized, placebo-controlled pilot study of dapsone plus rifampin versus placebo was conducted . RESULTS: Forty-one participants were recruited in a BU-endemic zone of Cote d'Ivoire . Thirty persons completed the 2-month trial: 15 were treated with placebo and 15 with dapsone and rifampin . On blinded evaluation of photographs of the ulcers, clinicians with experience examining BU judged that 82% of ulcers in the treatment group improved compared with 75% in the placebo group (P=0.51) . The median change in ulcer size was a decrease of 14.0 cm2 in the treatment group and a decrease of 2.5 cm2 in the placebo group (P=0.02), but initial ulcer sizes were larger in the treatment group (median 26.2 cm2) compared with the placebo group (median 4.8 cm2) (P=0.04) . CONCLUSIONS: Results of this study indicate that larger studies of antimycobacterial therapy of BU are warranted and can be successfully undertaken.

Cytotherapy, 2000, 2(4), 281 - 6
Mitomycin C as an alternative to irradiation to inhibit the feeder layer growth in long-term culture assays; Ponchio L et al.; BACKGROUND: Mitomycin C (MMC), an antitumoral antibiotic, has been described inhibiting the proliferation of different cell types in vitro . Since irradiation is commonly used to stop the cell growth of adherent cells in several experimental models, we aimed to define the optimal dose and incubation time of MMC capable of inhibiting the growth of murine fibroblasts, used as an adherent feeder layer in long-term hematopoietic culture assay . METHODS: M2 10B4 (both parental and engineered to produce human IL-3 and G-CSF) and Sl/Sl (engineered to produce human IL-3 and steel factor) murine fibroblast cell-lines, frequently used in LTC-IC assay, were incubated with increasing doses of MMC for either a short (3 h) or a long (16 h) period . The efficiency of MMC in stopping the cell growth was evaluated for 5 days following MMC removal . The effects of MMC treatment on human hematopoietic cells were studied using both LTC-IC and limiting dilution (CAFC) assays . RESULTS: The growth of M2 10B4 cells was stopped at 3 and 16 h in the presence of 20 microg/mL and 2 microg/mL of MMC, respectively while Sl/Sl fibroblasts required a lower dose of drug (2 and 0.2 microg/mL, respectively) . No significant difference was found between the number of LTC-IC or CAFC obtained from cultures containing irradiated or MMC-treated feeder cells . DISCUSSION: MMC inhibits the growth of murine fibroblasts used as adherent feeder cells in long-term culture assays, without interfering with the subsequent growth of co-cultured hemopoietic cells . Different cell types might present a different sensitivity to MMC and therefore a dose-response curve to MMC has to be obtained for each cell type of interest.

J Chemother, 1991 Jan, 3 Suppl 1, 231 - 2
Single-shot (short-term) prophylaxis with ceftriaxone in biliary surgery; Cimino F et al.; A short-term prophylaxis based on a one-shot injection 30 min before operation of 2 g ceftriaxone has been used in 20 cases, in patients undergoing elective cholecystectomy or biliary tract surgery for gall-stones . The prophylaxis with ceftriaxone proved to be successful in all patients.

Curr Mol Med, 2002 May, 2(3), 299 - 302
A new insight into the pathogenesis of filarial disease; Taylor MJ; Filariasis is a major public health problem throughout many regions of the tropics . The disease is caused by several species of filarial nematode including Wuchereria bancrofti and Brugia malayi, the agents of lymphatic filariasis, and Onchocerca volvulus, the cause of 'riverblindness' . Disease caused by these worms varies depending on the tissue location of the parasite, and is associated with episodes of acute and chronic inflammation . These pathologies, including elephantiasis and blindness, rank among the most disabling in the world . Studies aimed at characterizing the molecular nature of the inflammatory stimuli derived from filarial nematodes uncovered a long forgotten secret, their symbiont Wolbachia . LPS-like molecules from these intracellular bacteria are responsible for potent inflammatory responses from macrophages and in animal models of filarial disease . Wolbachia has also been associated with severe inflammatory reactions to filarial chemotherapy, being released into the blood following the death of the parasite . Recent studies in animal models even implicate Wolbachia in the onset of lymphodema and blindness . Taken together these studies suggest a major role for Wolbachia in the pathogenesis of filarial disease . It may be possible, through the use of antibiotic therapy, to clear worms of their bacteria, in the hope that this will prevent the onset and development of filarial pathology.

J Vet Intern Med, 2002 May-Jun, 16(3), 229 - 37
An immunologic investigation of canine eosinophilic bronchopneumopathy; Clercx C et al.; Immunologic variables in dogs with eosinophilic bronchopneumopathy (EBP) have not been extensively evaluated . The aim of this study was to determine immunoglobulin (Ig) concentrations and to perform phenotypic subtyping of lymphocytes in the bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) of 12 dogs with EBP at the time of diagnosis (TD) and to compare these data with those obtained in healthy dogs, as well as in EBP dogs after antibiotic therapy (TAB) and during corticosteroid treatment (TM) . Matched samples of serum and BALF were used to determine Ig concentrations (IgG, IgM, and IgA) by capture enzyme-linked immunosorbent assay (ELISA), from which a secretory index (SI) was calculated . Lymphocyte subpopulations were studied in the BALF and PB by flow cytometry . Log values of BALF IgM and IgA were significantly higher (0.64+/-0.05 and 1.06+/-0.13, respectively) in EBP dogs at TD than in controls and then tended to decrease at TM (0.55+/-0.03 and 1.02+/-0.17, respectively) . A calculated SI for IgA was not significantly increased . In the BALF of dogs with EBg the CD4: CD8 was significantly (P < .05) higher (22.6+/-30.3) than in controls (3.2+/-1.9), due to significantly higher CD4+ T cells and lower CD8+ T cells . At TM, the BALF T-cell percentages returned to normal (2.4+/-0.6) . We propose that the influx of eosinophils into the airway of dogs with EBP is at least in part mediated by cytokines derived from CD4+ T cells . Further studies of canine cytokines and chemokines will help determine whether canine EBP involves type I hypersensitivity mechanisms regulated by Th2 lymphocytes.

Bone Marrow Transplant, 2002 May, 29(9), 745 - 51
A randomized, multicenter study of G-CSF starting on day +1 vs day +5 after autologous peripheral blood progenitor cell transplantation; de Azevedo AM et al.; In order to assess the effect of delaying G-CSF administration after autologous peripheral blood progenitor cell (PBPC) transplantation on the duration of neutropenia, 87 patients were randomized to receive G-CSF 5 microg/kg/day starting on day +1 (n = 45) or +5 (n = 42) following PBPC transplantation, until recovery of the neutrophils . The duration of neutropenia (<0.5 x 10(9)/l) was shorter in the day +1 group (7 vs 8 days; P = 0.02), especially in patients receiving melphalan 200 mg/m(2) and CD34(+) cell doses >3.0 x 10(6)/kg . These patients had a later onset of neutropenia after transplant . There were no differences in time to neutrophil and platelet engraftment, or in the incidence of fever and documentation of infection . Although the duration of antibiotic therapy (7 vs 10.5 days; P = 0.01) and time to hospital discharge (13 vs 15 days; P = 0.02) were shorter in the day +1 group, these differences could not be predicted by the day of G-CSF initiation in multivariate analysis . Starting G-CSF on day +1 does not result in faster neutrophil engraftment but in later onset and consequently, slightly shorter duration of neutropenia in patients who receive melphalan 200 mg/m(2) and CD34(+) cell doses >3.0 x 10(6)/kg.

Am J Clin Oncol, 2002 Jun, 25(3), 308 - 12
Phase II trial of KW2189 in patients with advanced malignant melanoma; Markovic SN et al.; KW-2189, a semisynthetic duocarmycine antibiotic has been shown to exert antiproliferative effects against human tumor cell lines in vitro and animal tumor models in vivo . Phase I studies identified myelosuppression as the most noteworthy adverse effect . Presented are two concurrent phase II studies assessing the antitumor and toxicity profile of KW-2189 in metastatic melanoma patients . One of the studies accrued patients with a history of prior melanoma therapy and the other accrued patients without a history of prior melanoma therapy . KW-2189 was administered at 0.4 mg/m2 to previously treated patients and 0.5 mg/m2 to the previously untreated . Treatment was administered intravenously on day 1 of a 6-week cycle . Thirty previously untreated and 15 previously treated patients were accrued . The toxicity profiles of the both groups of patients were similar . Of the 15 previously treated patients, 8 completed once cycle of treatment, 2 completed 2 cycles, and 5 completed 3 cycles . Dose modification for neutropenia/ thrombocytopenia was necessary in six patients . Among the previously untreated cohort (30 patients), 16 completed 1 cycle, 5 completed 2 cycles, 4 completed 3 cycles, 3 completed 4 cycles, and 2 completed 6 cycles . Doses were modified (neutropenia or thrombocytopenia) in 11 patients . None of the 15 previously treated patients responded to therapy . Four patients remained stable during two cycles . Five of the previously untreated patients achieved a partial remission/regression . Response duration ranged from 2.8 to 16.6 months . Overall objective response rate was 17% . Regarding survival, one previously treated patient is still alive 2.9 years after study entry, and three previously untreated patients are still alive 1.6, 2.3, and 2.9 years after study entry . The 1-year survival rate for previously treated patients is 27% and for the untreated patients is 23% . In summary, the lack of significant antitumor activity of KW-2189 and its associated toxicity suggest that further testing of this regimen in patients with stage IV melanoma is not warranted.

Arch Intern Med, 2002 Jun 10, 162(11), 1229 - 36
Winter viruses: influenza- and respiratory syncytial virus-related morbidity in chronic lung disease; Griffin MR et al.; BACKGROUND: Chronic lung disease predisposes to serious consequences of respiratory viruses . While increasing influenza immunization rates in older adults signals an awareness of the impact of influenza, children with asthma are infrequently immunized . While respiratory syncytial virus (RSV) is recognized as an important target of vaccine development for infants, its impact on adults is underappreciated . METHODS: We performed a retrospective cohort study to estimate rates of hospitalizations, deaths, outpatient visits, and antibiotic courses due to influenza and RSV in persons with chronic lung disease in the Tennessee Medicaid program from 1995 to 1999 . Differences between study event rates when influenza was cocirculating with RSV and event rates when RSV was circulating alone were used to calculate influenza-attributable morbidity . Differences in rates when RSV was circulating alone and during summer months were calculated to assess the effect of RSV . RESULTS: Influenza- and RSV-associated hospitalizations were highest at the extremes of age . There were an estimated 8 and 23 hospitalizations per 1000 children younger than 5 years annually due to influenza and RSV, respectively . There were 23 and 18 hospitalizations, as well as 2 and 5 deaths per 1000 persons 65 years or older annually due to influenza and RSV, respectively . Both viruses were associated with an excess of outpatient visits in children, and antibiotic prescriptions in all age groups . CONCLUSION: Among persons with chronic lung disease, influenza virus and RSV accounted for 15% to 33% of acute respiratory hospitalizations in children, 7% to 9% of such hospitalizations in adults, and 9% of deaths in those 65 years or older.

J Am Board Fam Pract, 2002 May-Jun, 15(3), 214 - 7
Diagnosis and treatment of rosacea; Cohen AF et al.; BACKGROUND: Rosacea is a common skin disorder affecting middle-aged and older adults . Many patients mistakenly assume that early rosacea is normally aging skin and are not aware that effective treatments exist to prevent progression to permanent disfiguring skin changes . METHODS: The medical literature was reviewed on the pathophysiology, diagnosis, and treatment of rosacea . MEDLINE was searched using the key search terms "rosacea," "rhinophyma," "metronidazole," "Helicobacter pylori," and "facial redness." RESULTS AND CONCLUSIONS: Rosacea is easily diagnosed by physician observation, and physicians should initiate discussion of rosacea treatment with patients . Effective treatment of rosacea includes avoidance of triggers, topical and oral antibiotic therapy, both topical and oral retinoid therapy, topical vitamin C therapy, and cosmetic surgery.

Chir Ital, 2002 Mar-Apr, 54(2), 179 - 84
{Anastomosis dehiscence in anterior resection of the rectum with total excision of the mesorectum}; Tersigni R et al.; Anterior rectal resection with total mesorectal excision is currently regarded as the operation of choice in patients with neoplasms of the extraperitoneal rectum . This operation is associated with a significant incidence of anastomotic dehiscence . Some authors, therefore, advise the execution of a protective stoma . From 1987 to 2000, 241 patients with rectal neoplasma were submitted to radical surgery: 183 to anterior rectal resection (extraperitoneal neoplasms in 129 cases and intraperitoneal neoplasms in 54) and 58 to a Miles operation . The total incidence of anastomotic complications was 8.1% (15 patients) . In 12 cases (6.5%) a clinical dehiscence was observed, while in 3 patients (1.6%) an asymptomatic fistula was present . In the patients with symptomatic dehiscence a colostomy was performed in 5 cases (42%), while in 7 cases (58%) a conservative approach was adopted (total parenteral nutrition and antibiotic therapy), with complete healing of the fistula . The incidence of anastomotic complications was 9.3% in extraperitoneal neoplasms and 5.6% in intraperitoneal localizations . In relation to the anastomotic technique adopted, the incidence of dehiscences was 25% after 8 Knight-Griffen anastomoses, 16% after 12 manual anastomoses and 7.3% after 163 end-to-end mechanical anastomoses (P = NS) . The percentage of anastomotic complications was greater in the period from 1995 to 1997, compared to the period from 1987 to 1994 (12.6% vs 3.8%, P = NS), due to the routine execution of rectal resection in conjunction with total mesorectal excision, particularly at the beginning of the experience, in 1995 . In the last 36 cases from 1998 on the incidence of anastomotic complications was reduced to 8.3%, after the learning phase . No related mortality was observed . On the basis of our experience and the evidence reported in the international literature we do not think the execution of a protective stoma is justified after low and ultra-low colorectal anastomosis, except in selected cases.

Scand J Infect Dis, 2002, 34(3), 224 - 7
Fatal Aspergillus myocarditis following short-term corticosteroid therapy for chronic obstructive pulmonary disease; Carrascosa Porras M et al.; A 58-y-old man with chronic obstructive pulmonary disease (COPD) was admitted for treatment of an acute exacerbation of his illness . The patient's condition initially improved after therapy with oxygen, bronchodilators, antibiotic and methylprednisolone (40 mg every 8 h) was started . Soon afterwards, however, the patient's clinical status deteriorated and he died on the fifth hospital day . Post-mortem examination revealed unsuspected, isolated fungal myocarditis . The fungus was later identified as Aspergillus by indirect immunofluorescence . To our knowledge, this is the first case of fatal Aspergillus myocarditis related to short-term (< 1 week) steroid therapy in a COPD patient . We believe that this case provides further evidence to support the possibility of life-threatening infections in COPD patients who receive even a short course of corticosteroid treatment.

RN, 2001 Jan, 64(1), 42 - 6, 48; quiz 50
Sinusitis: when to treat and how; Klein L; When a common viral infection is mistaken for bacterial sinusitis, the antibiotics prescribed for it can contribute to the spread of antibiotic-resistant strains of bacteria . Here's what you need to know to correctly determine which type of sinusitis is making your patient miserable and treat it effectively.

Chem Biol, 2002 May, 9(5), 545 - 53
The methyl-branched fortifications of Mycobacterium tuberculosis; Minnikin DE et al.; Mycobacterium tuberculosis continues to be the predominant global infectious agent, annually killing over three million people . Recommended drug regimens have the potential to control tuberculosis, but lack of adherence to such regimens has resulted in the emergence of resistant strains . Mycobacterium tuberculosis has an unusual cell envelope, rich in unique long-chain lipids, that provides a very hydrophobic barrier to antibiotic access . Such lipids, however, can be drug targets, as exemplified by the action of the front-line drug isoniazid on mycolic acid biosynthesis . A number of these lipids are potential key virulence factors and their structures are based on very characteristic methyl-branched long-chain acids and alcohols . This review details the history, structure, and genetic aspects of the biosynthesis of these methyl-branched components, good examples of which are the phthiocerols and the mycocerosic and mycolipenic acids.

Hum Gene Ther, 2002 May 20, 13(8), 969 - 77
Enhanced ouabain resistance gene as a eukaryotic selection marker; Aints A et al.; Current selection markers allow selection by antibiotics or fluorescent/magnetic sorting by green fluorescent protein or membrane antigens . Antibiotic selection proceeds on a time scale of weeks, and flourescence-activated cell sorting requires complex equipment and may generate false-positive results when selection is performed too early after transduction with membrane markers . We have characterized an endogenous eukaryotic selection marker, the ouabain resistance gene (Oua(r)), which has the potential for quick and efficient in vitro selection of target cells . The Oua(r) used by us is derived from the rat alpha(1) isoform of Na(+),K(+)-ATPase, where leucine at position 799 is substituted for cysteine by targeted mutagenesis . This mutation confers resistance to more than 1 mM ouabain in vitro . We show that cells transfected with plasmid or transduced with a retrovirus vector encoding Oua(r) can be selected efficiently with ouabain in 48 hr and that a pure population of cells can be obtained . The ouabain resistance gene may be useful as a selection marker in general molecular biology, preclinical, and clinical applications because of its short selection time and also because of the safety of ouabain for human use.

J Am Geriatr Soc, 2002 Feb, 50(2), 290 - 9
Community-acquired pneumonia and do not resuscitate orders; Marrie TJ et al.; OBJECTIVES: From a cohort of patients with community-acquired pneumonia (CAP) who required admission to hospital, to describe the subset of patients having a do not resuscitate (DNR) order and to compare them with those who did not have such an order . DESIGN: Retrospective subset analysis of data from the pneumonia patient outcomes research team study . SETTING: Three hospitals in the United States and one in Canada . PARTICIPANTS: Hospitalized patients aged 18 and older with CAP . MEASUREMENTS: Sociodemographic features, severity of illness, antibiotic therapy, length of stay, mortality, admission to special care units, and mortality attributable to pneumonia . RESULTS: The 199 (14.9) of 1,339 inpatients with CAP who had a DNR order written within 24 hours of admission and an additional 96 (7.2) patients who had such an order written later were compared with the 1,044 who never had a DNR order . The 199 patients with an initial DNR and 96 later DNR were older (median age 81 and 78 vs 65 years, respectively; P< .001), more likely to be white (92.5 and 90.6 vs 84.8; P = .007), and more likely to have come from a nursing home or chronic care facility (53.8 and 31.3 vs 4.5; P< .001) . The two DNR groups received more antibiotics for a longer time than the never DNR patients . The DNR patients had longer lengths of stay than the never DNR patients (medians 9 and 12 vs 7 days) . There were 89 in-hospital deaths among the 1,339 patients, but only 11 of these were among patients who did not have a DNR order during the first 30 days (sensitivity, specificity, and positive and negative predictive values of a DNR order for in-hospital mortality were 87.6, 82.6, 26.4, and 98.9, respectively) . The 90-day mortality rates were 43.2 for the initial DNR group, 61.5 in the later DNR group, and 4.7 for the never DNR group (P< .001) . Pneumonia-attributable mortality accounted for most of the in-hospital deaths but did not differ by DNR status . Only 31.7 of the initial DNR patients and 24.0 of the later DNR patients were discharged home, versus 82.6 of the other patients (P< .001) . In a multivariate analysis, the following were predictive of initial DNR: age, nursing home care, active cancer, dementia, neuromuscular disorders, altered mental status, low systolic blood pressure, tachypnea, abnormal hematocrit, abnormal blood urea nitrogen, and absence of alcohol or intravenous drug abuse . In similar analyses of DNR at any time, additional predictors included aspiration, low white blood count, chronic pulmonary disease, cerebrovascular disease, and congestive heart failure . CONCLUSION: Most in-hospital pneumonia deaths occur in patients who have a DNR order . DNR orders written within 24 hours of admission primarily reflect comorbid status, whereas DNR orders written later during hospitalization reflect the futility of care plus comorbidity.

ANZ J Surg, 2002 May, 72(5), 339 - 43
Postdischarge clean wound infections: incidence underestimated and risk factors overemphasized; Reid R et al.; BACKGROUND: Wound infections are a leading cause of postoperative morbidity and a cost to both the individual and community . The surgeon now has a reduced appreciation of wound-infection rates because of shorter hospital stays and an increasing reliance on the primary care physicians.The incidence of wound infections which occurred following clean surgical procedures, as well as whether they could have been predicted by the known risk factors, were analysed in the present prospective study . METHODS: A prospective audit of the first 30 postoperative days following clean general surgical wounds was undergone, with inpatient assessment by a research nurse, and subsequent outpatient followup by patient telephone interview . RESULTS: Of 1964 clean wounds over a 30-month period, 98.5% were traced . The overall clean-wound infection rate was 12.6% (inpatient:4.5%; outpatient: 8.1%) . Inpatient infection rates(but not postdischarge wound-infection rates) were significantly correlated (P < 0.05)to the American Society of Anesthesiologists' rating, operation duration, preoperative day stay, and age . Infection rates varied with operation type: vascular (18.3%), breast (16.0%),abdominal (10.3%), hernia (8.0%), head and neck (7.1%) . CONCLUSIONS: The overall wound-infection rate is higher than previously described with two thirds of infections occurring after discharge . While inpatient wound-infection rates fit known risk factors, postdischarge wound-infection rates do not . Certain clean-wound operations have a higher incidence of infection than others . Consideration needs to be given to the identification of risk factors for postdischarge wound infections,and to further trials of prophylactic antibiotics in clean surgery.

Ann Thorac Cardiovasc Surg, 2002 Apr, 8(2), 97 - 101
Post harvest wound infection and patient's perception: comparative study between radial artery and saphenous vein harvest sites; Hata M et al.; INTRODUCTION: Despite renewed clinical interest in radial artery grafts (RA) for coronary artery bypass grafting, there is a paucity of controlled prospective data on its efficacy . We report on the rate of harvest related complications from a randomized radial artery study . METHODS: Two hundred eighty nine patients were divided into two groups . Group 1 received RA grafts (n=154 patients) and Group 2 (n=135 patients) received saphenous vein grafts (SVG) . Postoperative wound problems were assessed using a questionnaire . Postoperative harvest site infections were also carefully documented . RESULTS: In group 1, 6 of 154 (3.9%) patients had harvest site wound infections . Five of them improved by antibiotic therapy alone . In group 2, 24 of 135 (17.8%) patients had harvest site wound infections (p=0.001 vs . group 1) . Fifteen of these patients needed redressing due to discharge from the wound . One hundred forty-nine patients (96.7%) in group 1 answered that their hand function was normal on the questionnaire . Concerns and discomfort about the arm scars in the group 1 were of a similar value of 5.2% (8/154), respectively . In group 2, the incidence of those about the leg were 7.4% (10/135) and 11.9% (16/135), respectively . Although there was no significant difference in concerns about the scar, discomfort was significantly higher in group 2 compared with group 1 (p=0.0139) . CONCLUSIONS: RA harvest is associated with fewer wound infections and scar discomfort than SVG harvest . Radial artery harvest is almost acceptable in terms of a patient's perception . However, there are still patients who have some symptoms in the forearm after RA harvest . Long-term follow-up is necessary for patient's hand function.

Org Lett, 2002 May 30, 4(11), 1879 - 82
Total synthesis of ionomycin using ring-opening strategies; Lautens M et al.; {structure: see text} The total synthesis of the polyether antibiotic ionomycin, a calcium ionophore, is described . The synthesis demonstrates the utility of ring-opening methodologies as applied to the synthesis of polypropionate and deoxypolypropionate subunits, which are found in two of the four fragments in the synthesis.

Ophthalmic Surg Lasers, 2002 May-Jun, 33(3), 253 - 6
Two cases of Stenotrophomonas maltophilia endophthalmitis; Benian O et al.; Two cases of Stenotrophomonas maltophilia endophthalmitis, a rare cause of postoperative endophthalmitis, are reported in this study . Both of the patients underwent vitreus tap and intravitreal antibiotic injection . The therapy was augmented with systemic and subconjunctival injections . The response to this therapy protocol was excellent and the final visual acuity in both of the patients was 10/10 . The results are discussed and the literature, which consists of only 8 reported cases of Stenotrophomonas maltophilia endophthalmitis, is reviewed . Although endophthalmitis caused by this pathogen is a rare but important cataract surgery complication, with appropriate therapy, this clinical presentation can be cured without risk of reoccurrence.

Indian J Physiol Pharmacol, 2002 Jan, 46(1), 107 - 10
Drug utilization study in dermatology in a tertiary hospital in Delhi; Maini R et al.; The present study was undertaken to describe patterns of dermatological drug utilization in a tertiary hospital in Delhi by measuring WHO delineated drug use indicators . Six hundred and six prescriptions of dermatology out-patients were analyzed and the data collected were used to evaluate the following drug use indicators: average number of drug per prescription, average consultation time, percentage of drugs prescribed by generic name, percentage of encounters with an antibiotic prescribed, percentage of encounters with an injection prescribed and percentage of drug prescribed from the essential drugs list or formulary . The average number of drugs per prescription +/- SD was found to be 2.6 +/- 1.2, average consultation time +/- SD was 4.4 +/- 2.6 minutes, percentage of drug prescribed by generic name was 6.98, percentage of encounters with an antibiotic and injection prescribed were 46.86 and 6.76 respectively and 23% of the total drugs prescribed were from Delhi State Essential Drugs Formulary.

Vet Clin Pathol, 2001, 30(1), 2 - 7
International standardization of acute phase proteins; Skinner JG; Acute phase proteins (APPs) such as haptoglobin, serum amyloid A and pig major acute phase protein are plasma proteins that increase in concentration following infection, inflammation, or trauma . The circulating concentrations of these proteins in pigs and cattle can provide an objective measure of the health status of an animal and are increasingly being used as markers of animal health and welfare . Plasma concentrations of APPs are related to the severity of the underlying condition, and provide a ready means of evaluating both the presence and extent of disease . Haptoglobin, for example, has been used to identify both clinical and subclinical disease in animals, and for objectively monitoring antibiotic therapy in experimentally infected animals . Interpretative benefit can be further enhanced by the "acute phase index", derived from a mathematical formula that uses both positive- and negative-reacting APPs . Research suggests that in the future, assays for APPs will be used routinely to assess animal health, optimize production rates, monitor antibiotic therapy, detect diseases such as mastitis in dairy cows, and assess the health of animals at slaughter . These applications have considerable benefit for human food safety . Before APP assays can be applied in animal production on a worldwide basis, however, the calibration of assay methods must be harmonized to ensure that results obtained in the laboratory or on the farm are universally comparable and of consistent quality . In February 2000 the European Commission Directorate General Research Concerted Action was established to fulfill the task of international standardization of APPs . The Concerted Action Group consists of a network of 14 institutions representing 9 European countries . In this report, the background and goals of the Concerted Action Group, and scientific presentations from the group's first colloquium are described . In addition, the progress of the group to date and the standardization plan for the full 30-month duration of the Concerted Action are summarized.

Minerva Anestesiol, 2002 Apr, 68(4), 285 - 90
Pulmonary infection in the brain injured patient; Fabregas N et al.; Incidence of ventilator associated pneumonia (VAP) in brain injury patient ranges from 28 to 40 % . Brain injury may induce immunosuppression explaining why neurotraumapatients are at higher risk of developing early onset pneumonia . However, occurrence of pneumonia in brain injury patient has not been associated to higher mortality . Many methods such as selective digestive decontamination, early administration of antibiotics, continuous subglottic aspiration, improved initial choice and dosage of antibiotic, may be useful to prevent and treat VAP in brain injury.

J Am Anim Hosp Assoc, 2002 May-Jun, 38(3), 271 - 8
Positive intraoperative cultures and canine total hip replacement: risk factors, periprosthetic infection, and surgical success; Lee KC et al.; The results of closing intraoperative cultures from 27 canine total hip replacements (THR) were reviewed . The relationship between these culture results and presurgical and surgical factors, and the short- and long-term success of THR were assessed . Eleven out of 27 cases had a positive culture, but none of these 11 cases were diagnosed with periprosthetic infection at follow-up examination . The duration of the clinical signs of hip disease prior to THR was significantly greater for those cases with a positive culture (P=0.034) . The incidence of positive cultures was not related to surgical success.

Am J Otolaryngol, 2002 May-Jun, 23(3), 177 - 80
Otalgia as the sole presenting manifestation of subdural hematoma; Zaidat OO et al.; A case is reported of a 57-year-old man with sudden development of nontraumatic left-sided otalgia without any localizing features on otolaryngologic or neurologic examinations . The condition persisted despite empirical antibiotic therapy and simple analgesics . A subsequent computed tomography of the head revealed a subacute left frontoparietal subdural hematoma that was confirmed on magnetic resonance imaging . Neurosurgical drainage was performed with complete symptom resolution . This case report illustrates a possible rare sole presenting manifestation of subdural hematoma . This condition should be considered early in cases of otalgia if no causes are deduced after extensive otolaryngologic evaluation .

J Fam Pract . 2002 May;51(5):465.
Associations of pacifier use, digit sucking, and child care attendance with cessation of breastfeeding; Levy SM et al.; OBJECTIVE: Breast milk is the recommended method of nutrition for newborns and infants . Several studies have investigated factors associated with the cessation of breast-feeding . This study assessed the associations between pacifier use, digit sucking, childcare attendance, and breastfeeding cessation among 1387 infants in the Iowa Fluoride Study . STUDY DESIGN: This was a longitudinal questionnaire survey . Mothers completed mailed questionnaires sent at infant ages 6 weeks, 3 months, and 6 months . POPULATION: Parents were recruited postpartum at 8 Iowa hospitals . OUTCOMES MEASURED: Survival analysis (using Cox proportional hazards model) assessed the time covariate effects of pacifier use, digit sucking, and child care attendance on cessation of breastfeeding, while adjusting for other possible confounding variables (not planning to breastfeed, maternal smoking, infants' sex and antibiotic use, maternal and paternal age and education, and income group) . RESULTS: Percentages of women who did any breastfeeding were 46%, 36%, and 27%, at 6 weeks, 3 months, and 6 months, respectively . Percentages using pacifiers were 81%, 71%, and 59% . Combinations of pacifier use and digit sucking for various levels of child care had statistically significant associations with cessation of breastfeeding, with the effect being strongest for pacifier users and digit suckers with no child care days (hazard ratio = 1.88; 95% CI, 1.36-2.62) . CONCLUSIONS: Pacifier use and digit sucking were associated with cessation of breastfeeding, with results dependent on the level of childcare attendance . The strongest associations were found for those not attending childcare and for combined use of pacifier with digit sucking.

Int J Clin Pract, 2002 Apr, 56(3), 181 - 3
Management of chronic osteomyelitis in a developing country using ceftriaxone-PMMA beads: an initial study; Alonge TO et al.; Chronic osteomyelitis is a debilitating disease that is fairly common in developing countries . Various operative techniques have been adopted in the management of this disease but there have been few reports of their use in Africa . In this report, we present our experience of the use of a modified two-staged Belfast operation in patients with chronic osteomyelitis in Ibadan, Nigeria . An important modification of the procedure was the substitution of gentamicin beads (Septopal) with ceftriaxone-polymethylmethacrylate (PMMA) beads at the saucerised segment of bone at the first stage . Thirty-four patients with chronic osteomyelitis had the two-stage Belfast operation in 35 long bones; of these, 32 patients had ceftriaxone-PMMA antibiotic beads inserted at the saucerised segment of bone at the first stage, while the other two patients had gentamicin beads inserted . One of the two patients who had gentamicin beads had a residual collection of pus at second stage surgery but, following a repeat debridement, the cavity was rid of infection . There was recurrence of infection in three patients (8.6%) who had a suction drain inserted at the first stage and in six patients (17.1%) who had no suction drain at the first stage . The locally produced ceftriaxone-PMMA beads were found to be as efficient as the commercially available gentamicin beads in eluting antibiotics locally, thereby eliminating the residual infection in the bone cavities after the first stage . Another important outcome was a fourfold saving in cost in choosing to use ceftriaxone-PMMA beads rather than gentamicin beads.

Indian J Exp Biol, 2001 Dec, 39(12), 1235 - 42
Cytogenetical effects of sonication in mice and their modulations by actinomycin D and a homeopathic drug, Arnica 30; Chakrabarti J et al.; Experiments were designed to examine if Actinomycin D, an antibiotic, and Amica 30, a homeopathic drug used against shock and injury, can ameliorate cytogenetic damage induced by single or multiple exposures to ultrasonication . Separate sets of healthy mice were directly exposed to sonication for two minutes either once or they received multiple exposures at an interval of 20 days . The mice were then assessed at different intervals, against suitable controls, using parameters like chromosome aberrations (CA), mitotic index (MI), sperm head anomaly (SHA) and micronucleated erythrocytes (MNE) . Separate groups of sonicated mice were either orally administered with Arnica 30 (alcohol 30 in control) or injected intramuscularly with Actinomycin-D (AMD) . Elevated frequencies of CA, MI, MNE and SHA were noted in sonicated series . AMD had genotoxic effects of its own and also had additive effects on sonication induced genotoxicity . Sonicated mice fed with Arnica 30 showed appreciably reduced genotoxicity as against alcohol 30 and distilled water fed controls, thereby showing ameliorating effect which may have human application.

Reg Anesth Pain Med, 2002 May-Jun, 27(3), 316 - 8
Periosteal infusion of bupivacaine/morphine post sternal fracture: a new analgesic technique; Duncan MA et al.; BACKGROUND AND OBJECTIVES: Sternal fracture pain is severe and is difficult to alleviate due to the forces acting on the chest wall during respiration . We describe a continuous infusion regional analgesic technique for pain due to sternal fracture . CASE REPORT: A 47-year-old woman presented with a spontaneous sternal fracture, precluding effective coughing . Diclofenac and increasing doses of opioids did not give adequate pain relief and led to opioid toxicity . Two brief periods of analgesia were achieved with deep subcutaneous infiltration of bupivacaine . An epidural catheter was positioned periosteally, and an infusion of bupivacaine was commenced at 5 mL/h, achieving long-lasting analgesia . The bupivacaine concentration was reduced in a stepwise fashion from 0.5% to 0.25% and was changed to levobupivacaine after 3 days . Adding morphine (5 mg/60 mL levobupivicaine) permitted a reduction in infusion rate . The catheter was removed after 14 days because a local infection developed that resolved uneventfully with antibiotic therapy . CONCLUSIONS: Continuous infusion of local anesthetic and opioid to a sternal fracture site using a periosteally positioned catheter led to successful analgesia and hence improved respiratory function . Clinicians should consider placing a periosteal catheter when pain associated with sternal fracture cannot be adequately controlled with conventional methods.

NeuroRehabilitation, 2002, 17(1), 23 - 31
Induced dedifferentiation: a possible alternative to embryonic stem cell transplants; Becker RO; Induction of local tissue regeneration in the human would best be accomplished if the patient's own cells at the desired site could be caused to dedifferentiate into the required embryonic stem cells . A system involving the electrical iontophoretic introduction of free silver ions into human wounds for their antibiotic effect has been in clinical use since 1975 . In addition to a major antibiotic effect, the technique was found to produce the regeneration of all local tissues, apparently by stimulating dedifferentiation of mature human cells . More recently the use of a newly developed silvered nylon fabric has been found to have similar results without the need for electrical parameters . The results of a preliminary laboratory and clinical study of this material are presented.

J Hepatobiliary Pancreat Surg, 2002, 9(1), 93 - 7
Technical considerations to maintain a low frequency of postoperative biliary stent-associated infections; Schwarz RE; BACKGROUND/PURPOSE: In patients with malignant biliary obstruction, preoperative biliary tract manipulation and stent drainage has been associated with increased infectious complications and mortality . METHODS: Between October 1996 and September 2000, 36 patients underwent bilioenteric anastomosis by a single surgeon . Diagnoses included pancreatic and other periampullary cancers (67%), benign obstruction (14%), hilar cholangiocarcinoma (8%), and other malignancies (11%) . Preoperative bile duct manipulation had been done in 72%, and a biliary stent had been placed in 58% . Two-thirds of patients underwent major resection and the remainder were treated with internal biliary bypass . All patients had received preoperative bowel cleansing and perioperative antibiotics . Bile ducts were left clamped after incision until anastomotic completion to avoid biliary spillage, and drains were generally not placed . RESULTS: Intraoperative bile cultures were positive in 73% . This was strongly linked to the presence of a stent ( P = 0.0004), or prior duct manipulation ( P = 0.002) . There were 3 postoperative, unrelated deaths in patients after palliative bypass (overall mortality rate, 8.3%) . Postoperative infections occurred in 7 patients (19%), of which three were due to a similar organism . There was one biliary leak, no pancreatic leak, and no intraabdominal abscess . CONCLUSIONS: Appropriate preoperative antibiotic coverage, preventing intraoperative peritoneal bile contamination through temporary bile duct occlusion, and avoiding routine drain placement, are strongly suggested for patients in whom preoperative biliary manipulation has taken place.

J Vasc Surg, 2002 May, 35(5), 923 - 9
Doxycycline in patients with abdominal aortic aneurysms and in mice: comparison of serum levels and effect on aneurysm growth in mice; Prall AK et al.; OBJECTIVE: Doxycycline has been shown to inhibit aneurysm formation in a rodent model of abdominal aortic aneurysm (AAA) . The doses necessary for this inhibition (6 mg/kg) are much higher than the standard antibiotic doses (1 to 1.5 mg/kg) used in humans . Because the side effects associated with doxycycline are dose related, whether patients would tolerate doses that are four to six times higher than normal is unclear . Also unclear is whether the serum levels necessary in these animal models can be safely achieved in patients . The purposes of this study were to determine the serum concentrations necessary to inhibit aneurysm formation in a mouse model of AAA and to compare them with the plasma concentrations in patients with AAA with a standard dose of doxycycline . METHODS: Four groups of 10 mice of C57BL/6 strain were given doxycycline (0, 10, 50, and 100 mg/kg) beginning at 7 weeks of age . At 8 weeks of age, the mice underwent AAA induction through bathing periadventitial aortic tissue with 0.25 mol/L CaCl(2) . Blood samples were taken 10 weeks after surgery to assess the levels of doxycycline . Aortic size was measured at AAA induction and at death with a videomicrometer . Fourteen patients with diagnosed AAA were given 100 mg of doxycycline twice a day for at least 3 months . Blood samples to determine the plasma levels of the drug were taken at 3 or 6 months . The circulating levels of doxycycline for mice and humans were assessed with high-performance liquid chromatography . RESULTS: The changes in aortic size and circulating levels of doxycycline in the AAA murine model are reported . Doses of 10, 50, and 100 mg/kg accounted for a 33%, 44%, and 66% reduction of the aneurysmal growth in the mice, respectively . In patients, the circulating doxycycline levels ranged from 1.8 to 9.42 microg/mL (mean, 4.14 +/- 0.557), values similar to those obtained in mice . CONCLUSION: The circulating doxycycline levels of the patients are comparable with those achieved in mice . Doxycycline accounts for an inhibition of 33% to 66% of the aortic growth . The findings suggest that standard doxycycline doses could inhibit AAA growth in humans.

Clin Infect Dis, 2002 Jun 1, 34(11), 1440 - 8 Epub 2002 May 07.
Once-daily intravenous cefazolin plus oral probenecid is equivalent to once-daily intravenous ceftriaxone plus oral placebo for the treatment of moderate-to-severe cellulitis in adults; Grayson ML et al.; A once-daily regimen of cefazolin (2 g intravenously {iv}) plus probenecid (1 g by mouth) was compared with a once-daily regimen of ceftriaxone (1 g iv) plus oral placebo in a randomized, double-blind equivalence trial of home-based therapy for moderate-to-severe cellulitis in adults . For the assessable recipients of cefazolin-probenecid (n=59) and ceftriaxone-placebo (n=57), clinical cure occurred at the end of treatment in 86% and 96% (P=.11), respectively, and was maintained at 1 month of follow-up in 96% and 91% (P=.55), respectively . The mean number of treatment doses (+/-standard deviation) given was similar in the 2 treatment arms (6.97+/-2.6 for cefazolin-probenecid and 6.12+/-2.1 for ceftriaxone-placebo; P=.06) . The median antibiotic trough concentrations were 2.35 microgram/mL for cefazolin and 15.45 microgram/mL for ceftriaxone . Patients in the 2 treatment arms were similar with regard to overall rates of adverse reaction (P=.15), but nausea was more common among those in the cefazolin-probenecid arm (P=.048) . The once-daily regimen of cefazolin-probenecid is a cheap, practical, and effective treatment option for moderate-to-severe cellulitis, and it avoids the need to use third-generation cephalosporins in most patients.

Med J Malaysia, 2001 Dec, 56(4), 471 - 7
Melioidosis of the head and neck; Lim WK et al.; Melioidosis is a potentially deadly infection that can affect any organ system . Reports of melioidosis of the ENT/head and neck region are relatively uncommon . Four cases are presented: (i) parotid abscess evolving into necrotising fasciitis, (ii) acute sinusitis and parapharyngeal cellulitis resulting in upper airway obstruction, (iii) acute suppurative lymphadenitis (iv) and chronic suppurative otitis media causing meningoencephalitis . Three of the four cases are believed to be unique, as a literature review of melioidosis in ENT/head and neck is also presented . Some practical issues of management are also discussed . Not suspecting melioidosis does not change contemporary empirical broadspectrum antibiotic therapy . The value of suspicion or on confirmation of diagnosis lies in anticipating and planning for rapid change.

Br J Gen Pract, 2002 May, 52(478), 401 - 9
The natural history of acute cough in children aged 0 to 4 years in primary care: a systematic review; Hay AD et al.; Professional and parental uncertainty regarding the natural history of cough and respiratory tract infection (R77) in pre-school children may in part be responsible for the high consultation, reconsultation, and antibiotic prescribing rates in this age group . The aim of the study was to review the evidence about the natural history of acute cough in children aged between 0 and 4 years presenting to primary care in terms of illness duration and complications . The study was a systematic review, with qualitative and quantitative data synthesis, of control and placebo arms of systematic reviews, randomised controlled trials (RCTs), and cohort studies set in primary care . Searches were done of MEDLINE (between 1966 and June 1998), EMBASE (between 1988 and September 1998), and the Cochrane Library databases, using the MeSH terms 'respiratory tract infection, 'cough, and 'bronchitis, and the textwords 'cough' 'bronchitis, and 'chest infection, limited to children aged between 0 and 4years, and English language articles . Eight RCTs and two cohort studies met the review criteria . At one week, 75% of children may have improved but 50% may be still coughing and/or have a nasal discharge . At two weeks up to 24% of children may be no better . Within two weeks of presentation, 12% of children may experience one or more complication, such as rash, painful ears, diarrhoea, vomiting, or progression to bronchitis/pneumonia . This review offers parents and clinicians more prognostic information about acute cough in pre-school children . Illness duration may be longer and complications higher than many parents and clinicians expect . This may help to set more realistic expectations of the illness and help parents to decide when and if to reconsult . This information may be useful to those designing patient information and self-help resources.

N Z Med J, 2002 Mar 22, 115(1150), 124 - 6
Infective endocarditis--a twelve year surgical outcome series; McKay G et al.; AIM: To review the clinical course and outcome of patients with infective endocarditis proceeding to surgical treatment in the South Island of New Zealand . METHODS: A retrospective review of all cases of infective endocarditis requiring cardiac surgery, excepting homograft replacement between 1989 and June 2001 was performed . All patients treated at both cardiothoracic units over this time frame in the South Island of New Zealand were included . RESULTS: A total of 29 patients, ten females and nineteen males, age range 31-79 years (mean 55) underwent surgery . 27 patients had native valve endocarditis, two infection of prosthetic valves . A variety of causative micro-organisms were isolated, and all patients received aggressive intravenous antibiotic therapy . Heart failure was the predominant indication for surgical intervention . Fifteen patients underwent aortic, nine mitral, three combined and two replacement of infected prosthetic valves . There were five peri-operative deaths (17% mortality) and significant morbidity in a further eleven patients (38%) . Of the 23 survivors available to follow-up none have recurrent endocarditis, with an average disease free survival of 35 months . CONCLUSIONS: Patients who require valve surgery for endocarditis have significant peri-operative morbidity and mortality . Long-term outcome in survivors, however, is extremely good with a prognosis similar to those undergoing elective valve replacement surgery . Mycotic cerebral aneurysms are an emerging important cause of early deaths.

Clin Pharmacol Ther, 2002 May, 71(5), 325 - 33
Tissue distribution of imipenem in critically ill patients; Tegeder I et al.; BACKGROUND AND METHODS: Imipenem is a broad-spectrum antibiotic used mainly for serious infections in critically ill patients . Because the infection originates mostly from a certain tissue, we assessed tissue concentrations of imipenem using microdialysis in patients in intensive care with serious infections compared with healthy volunteers . Most patients were >60 years old and had renal failure; most patients also had impaired liver, heart, or lung function . RESULTS: Muscle and subcutaneous tissue concentrations in patients (maximum of 2.3 +/- 1.5 microg/mL for both muscle and subcutaneous tissue) were significantly lower than those in healthy subjects (maximum of 12.8 +/- 1.6 and 10.7 +/- 1.0 microg/mL for muscle and subcutaneous tissue) . The tissue distribution rate constants for muscle and subcutaneous tissue were also significantly lower in patients (1.95 +/- 0.6 and 1.1 +/- 0.2 h(-l), respectively) than in healthy subjects (5.2 +/- 1.0 and 6.6 +/- 1.7 h(-1), respectively), meaning that tissue distribution in patients was reduced and retarded . Values for area under the plasma concentration-time curve did not significantly differ between patients and healthy subjects (37.4 +/- 5.9 microg . h/mL and 46.0 +/- 4.4 microg . h/mL, respectively,) although the elimination of imipenem in patients was prolonged (clearance, 6.3 +/- 0.8 L/h and 13.2 +/- 1.4 L/h in patients and healthy subjects, respectively) . CONCLUSIONS: Our data suggest that the amount and velocity of imipenem tissue distribution in seriously ill patients is reduced compared with those values in healthy volunteers . Dose adjustments that are exclusively based on plasma concentration data may therefore be misleading and may result in potential underdosing.

J Biol Chem, 2002 Aug 9, 277(32), 28474 - 82 Epub 2002 May 14.
Identification of the catalytic residues of alpha-amino acid ester hydrolase from Acetobacter turbidans by labeling and site-directed mutagenesis; Polderman-Tijmes JJ et al.; The alpha-amino acid ester hydrolase from Acetobacter turbidans ATCC 9325 is capable of hydrolyzing and synthesizing the side chain peptide bond in beta-lactam antibiotics . Data base searches revealed that the enzyme contains an active site serine consensus sequence Gly-X-Ser-Tyr-X-Gly that is also found in X-prolyl dipeptidyl aminopeptidase . The serine hydrolase inhibitor p-nitrophenyl-p'-guanidino-benzoate appeared to be an active site titrant and was used to label the alpha-amino acid ester hydrolase . Electrospray mass spectrometry and tandem mass spectrometry analysis of peptides from a CNBr digest of the labeled protein showed that Ser(205), situated in the consensus sequence, becomes covalently modified by reaction with the inhibitor . Extended sequence analysis showed alignment of this Ser(205) with the catalytic nucleophile of some alpha/beta-hydrolase fold enzymes, which posses a catalytic triad composed of a nucleophile, an acid, and a base . Based on the alignments, 10 amino acids were selected for site-directed mutagenesis (Arg(85), Asp(86), Tyr(143), Ser(156), Ser(205), Tyr(206), Asp(338), His(370), Asp(509), and His(610)) . Mutation of Ser(205), Asp(338,) or His(370) to an alanine almost fully inactivated the enzyme, whereas mutation of the other residues did not seriously affect the enzyme activity . Circular dichroism measurements showed that the inactivation was not caused by drastic changes in the tertiary structure . Therefore, we conclude that the catalytic domain of the alpha-amino acid ester hydrolase has an alpha/beta-hydrolase fold structure with a catalytic triad of Ser(205), Asp(338), and His(370) . This distinguishes the alpha-amino acid ester hydrolase from the Ntn-hydrolase family of beta-lactam antibiotic acylases.

Int J Dermatol, 2002 Mar, 41(3), 182 - 4
Cutaneous involvement of dermatomyositis can respond to Dapsone therapy; Cohen JB; BACKGROUND: Dapsone (4,4-diaminodiphenylsulfone) is a sulfone antibiotic used in the treatment of leprosy, but dermatologists more commonly utilize its anti-inflammatory properties particularly directed against leukocytes to treat various bullous disorders, erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, cutaneous vasculitis, and cutaneous forms of lupus erythematosus . The cutaneous manifestations of dermatomyositis are often resistant to antimalarial and immunosuppressive therapies . METHODS: Two patients with cutaneous dermatomyositis unresponsive to combination therapy with prednisone, hydroxychloroquine, quinacrine, and immunosuppressive medications had Dapsone added to their therapy . RESULTS: Both patients showed rapid improvement with the addition of Dapsone . Each had an exacerbation of their cutaneous dermatomyositis on Dapsone with withdrawal and subsequent improvement when the Dapsone was reinstituted . CONCLUSIONS: Dapsone therapy for cutaneous dermatomyositis may have a wider role in treatment for these patients refractory to prednisone and antimalarial therapy.

J Endovasc Ther, 2002 Apr, 9(2), 212 - 7
Aortoesophageal fistula secondary to mycotic thoracic aortic aneurysm: endovascular repair and transhiatal esophagectomy; Van Doorn RC et al.; PURPOSE: To report a case of aortoesophageal fistula secondary to a mycotic thoracic aortic aneurysm (TAA) successfully repaired by stent-grafting of the descending thoracic aorta . CASE REPORT: A 66-year-old woman with a recent history of hemicolectomy for colon cancer complicated by postoperative infection presented with midthoracic pain, fever, hoarseness, and blood chemistries consistent with an inflammatory process . Imaging showed a widened mediastinum and displacement of the trachea due to a mycotic thoracic aneurysm; endoscopy confirmed a large fistula in the esophageal wall . There was no active bleeding, so an Excluder thoracic endograft was positioned in the aortic arch, partially covering the left subclavian artery origin . Three days later, a transhiatal esophagectomy was performed . Intravenous antibiotic therapy was continued for 6 weeks . At 18 months, a minithoracotomy was performed because of extreme dyspnea . An aneurysm sac hygroma was drained in the thoracic cavity . At 2 years, the patient was well, and there were no signs of infection or dyspnea . CONCLUSIONS: Along with a transhiatal esophagectomy, we suggest that endovascular stent-grafting has a place as a minimally invasive technique in the treatment of aortoesophageal fistula secondary to aneurysm of the thoracic aorta.

Bioelectrochemistry, 2002 May 15, 56(1-2), 81 - 3
Electrochemical sensing of DNA-adriamycin interactions; Piedade JA et al.; Adriamycin, a cancerostatic anthracycline antibiotic, causes considerable death of tumour cells, together with the induction of breaks in DNA single and double strands . The interaction of this compound with DNA was investigated using an electrochemical DNA-biosensor . Adriamycin intercalation in DNA disrupts the double helix and the detection of guanine and 8-oxoguanine could mimic one possible mechanism for the in vivo adriamycin drug action.

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