Antibiotics

Clin Pharmacol Ther, 2001 Jul, 70(1), 58 - 65
The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide; Niemi M et al.; OBJECTIVE: Our objective was to study the effects of the macrolide antibiotic clarithromycin on the pharmacokinetics and pharmacodynamics of repaglinide, a novel short-acting antidiabetic drug . METHODS: In a randomized, double-blind, 2-phase crossover study, 9 healthy volunteers were treated for 4 days with 250 mg oral clarithromycin or placebo twice daily . On day 5 they received a single dose of 250 mg clarithromycin or placebo, and 1 hour later a single dose of 0.25 mg repaglinide was given orally . Plasma repaglinide, serum insulin, and blood glucose concentrations were measured up to 7 hours . RESULTS: Clarithromycin increased the mean total area under the concentration-time curve of repaglinide by 40% (P <.0001) and the peak plasma concentration by 67% (P <.005) compared with placebo . The mean elimination half-life of repaglinide was prolonged from 1.4 to 1.7 hours (P <.05) by clarithromycin . Clarithromycin increased the mean incremental area under the concentration-time curve from 0 to 3 hours of serum insulin by 51% (P <.05) and the maximum increase in the serum insulin concentration by 61% (P <.01) compared with placebo . No statistically significant differences were found in the blood glucose concentrations between the placebo and clarithromycin phases . CONCLUSIONS: Even low doses of the cytochrome P4503A4 (CYP3A4) inhibitor clarithromycin increase the plasma concentrations and effects of repaglinide . Concomitant use of clarithromycin or other potent inhibitors of CYP3A4 with repaglinide may enhance its blood glucose-lowering effect and increase the risk of hypoglycemia.

Antimicrob Agents Chemother, 2001 Aug, 45(8), 2198 - 203
Growth and development of tetracycline-resistant Chlamydia suis; Lenart J et al.; Tetracycline (TET) is a front-line antibiotic for the treatment of chlamydial infections in both humans and animals, and the emergence of TET-resistant (Tet(r)) Chlamydia is of significant clinical importance . Recently, several Tet(r) chlamydial strains have been isolated from swine (Sus scrofa) raised in production facilities in Nebraska . Here, the intracellular development of two Tet(r) strains, R19 and R27, is characterized through the use of tissue culture and immunofluorescence . The strains grow in concentrations of up to 4 microg of TET/ml, while a TET-sensitive (Tet(s)) swine strain (S45) and a strain of the human serovar L2 (LGV-434) grow in up to 0.1 microg of TET/ml . Although inclusions form in the presence of TET, many contain large aberrant reticulate bodies (RBs) that do not differentiate into infectious elementary bodies . The percentage of inclusions containing typical developmental forms decreases with increasing TET concentrations, and at 3 microg of TET/ml 100% of inclusions contain aberrant RBs . However, upon removal of TET the aberrant RBs revert to typical RBs, and a productive developmental cycle ensues . In addition, inclusions were found that contained both C . suis R19 and Chlamydia trachomatis L2 after sequential infection, demonstrating that two biologically distinct chlamydial strains could both develop within a single inclusion.

Chem Biol, 2001 Jul, 8(7), 713 - 23
Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes; Caffrey P et al.; BACKGROUND: The polyene macrolide amphotericin B is produced by Streptomyces nodosus ATCC14899 . Amphotericin B is a potent antifungal antibiotic and has activity against some viruses, protozoans and prions . Treatment of systemic fungal infections with amphotericin B is complicated by its low water-solubility and side effects which include severe nephrotoxicity . Analogues with improved properties could be generated by manipulating amphotericin biosynthetic genes in S . nodosus . RESULTS: A large polyketide synthase gene cluster was cloned from total cellular DNA of S . nodosus . Nucleotide sequence analysis of 113193 bp of this region revealed six large polyketide synthase genes as well as genes for two cytochrome P450 enzymes, two ABC transporter proteins, and genes involved in biosynthesis and attachment of mycosamine . Phage KC515-mediated gene disruption was used to show that this region is involved in amphotericin production . CONCLUSIONS: The availability of these genes and the development of a method for gene disruption and replacement in S . nodosus should allow production of novel amphotericins . A panel of analogues could lead to identification of derivatives with increased solubility, improved biological activity and reduced toxicity.

Scand J Infect Dis, 2001, 33(6), 470 - 1
Pacemaker endocarditis: report of 2 cases; Montejo M et al.; Two cases of endocarditis due to placement of a pacemaker are reported . In both cases administration of intravenous antibiotic and removal of the entire pacing system was successful.

No Shinkei Geka, 2001 May, 29(5), 415 - 20
{The early hemorrhage and development of a bacterial aneurysm after a cerebral ischemic attack caused by a septic embolism--a case report}; Wakamoto H et al.; A 71-year-old female was admitted with the complaints of dysarthria and right hemiparesis . CT scan revealed subarachnoid hemorrhage in the left cerebral sulcus . The first angiography was performed 3 days after the onset and left carotid angiography revealed a small aneurysm arising from the left middle cerebral artery . After 3 weeks of antibiotic therapy, the second angiography showed the aneurysm to be clearly enlarged, so it was resected . The patient complained of marked dysarthria a day after the operation and CT scan revealed a new infarction in the right frontal lobe . The third angiography showed an aneurysm arising from the right middle cerebral artery and the fact that two peripheral arteries of the aneurysm had disappeared 3 weeks after the first operation . The second operation was performed and a bacterial aneurysm was resected . The patient left the hospital without any neurological deficits . Septic embolism is the most important complication of infective endocarditis and it is usually presented with subarachnoid hemorrhage and intracerebral hemorrhage caused by ruptured bacterial aneurysms . In this case the septic embolism occurred two times . At each time cerebral ischemic attacks were presented . The reason why this case presented with ischemic symptoms was suspected to be that embolisms occurred at the trifurcation of the distal middle cerebral arteries . We were able to detect a bacterial aneurysm angiographically 3 days after the ischemic attack and we suspected that a bacterial aneurysm had been able to develop within 3 days after the septic embolism.

Arch Pediatr Adolesc Med, 2001 Jun, 155(6), 641 - 7
Steroids for otitis media with effusion: a systematic review; Butler CC et al.; BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss with associated delayed language development in children . Treatment remains controversial . OBJECTIVE: To examine evidence for or against treating OME with systemic or topical nasal steroids . DATA SOURCES: We searched the Cochrane Controlled Trials Register using the terms otitis media; otitis media with effusion; glue ear; or OME and steroids; glucocorticoids; glucocorticoids, synthetic; glucocorticoids, topical; or anti-inflammatory agents, steroidal; or various combinations of these terms . EMBASE and MEDLINE were also searched . STUDY SELECTION: Randomized controlled trials of oral and topical nasal steroids, either alone or in combination with another agent such as an antibiotic, were included . Ten studies met the inclusion criteria . DATA EXTRACTION: Data extraction and methodological quality assessment were performed by the 2 of us (C.C.B . and J.H.v.d.V.) independently, using standardized methods described in the Cochrane Collaboration Handbook . DATA SYNTHESIS: The odds ratio for OME persisting after short-term follow-up in children treated with oral steroids compared with a control was 0.22 (95% confidence interval, 0.08 = 0.63), and was 0.32 (95% confidence interval, 0.20 = 0.52) for children treated with oral steroids plus an antibiotic compared with a control plus an antibiotic . Trends favored steroids for most other comparisons, but confidence intervals included unity . Trends favored steroids for most other comparisons, but confidence intervals included unity . CONCLUSIONS: Steroids alone or combined with an antibiotic lead to a quicker resolution of OME in the short-term . However, there is no evidence for a long-term benefit from treating hearing loss associated with OME with either oral or topical nasal steroids . These treatments are, therefore, not recommended.

J Immunother, 2001 Mar, 24(2), 188 - 192
A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Effect of Nystatin on the Development of Oral Irritation in Patients Receiving High-Dose Intravenous Interleukin-2; Ohnmacht GA et al.; SUMMARY: Interleukin-2 (IL-2) has been used to treat patients with metastatic melanoma and renal cell cancer for nearly two decades, and much progress has been made in ameliorating its adverse effects . One bothersome adverse effect, oral pain or oral irritation, is usually treated with an oral antifungal antibiotic, nystatin . The authors performed a prospective, randomized, double-blind, placebo-controlled trial involving 64 patients to evaluate the effect of prophylactic administration of nystatin or placebo on the development of oral irritation in patients receiving high-dose intravenous IL-2 . No difference was found between patients randomized to receive nystatin or placebo in their rates of development of oral irritation, the severity of IL-2 adverse effects, the duration of their treatment, the rate of development of positive studies for oral yeast, or their pattern of experiencing other adverse effects . Thus, patients who receive high-dose intravenous IL-2 should not be treated prophylactically with nystatin to prevent oral irritation, and clinicians should seek evidence of the presence of oral thrush before using antifungal agents to treat oral pain in these patients.

Virology, 2001 Jul 20, 286(1), 182 - 96
Analysis of the first complete DNA sequence of an invertebrate iridovirus: coding strategy of the genome of Chilo iridescent virus; Jakob NJ et al.; Chilo iridescent virus (CIV), the type species of the genus Iridovirus, a member of the Iridoviridae family, is highly pathogenic for a variety of insect larvae . The virions contain a single linear ds DNA molecule that is circularly permuted and terminally redundant . The coding capacity and strategy of the CIV genome was elucidated by the analysis of the complete DNA nucleotide sequence of the viral genome (212,482 bp) using cycle sequencing by primer walking technology . Both DNA strands were sequenced independently and the average redundancy for each nucleotide was found to be 1.85 . The base composition of the viral genomic DNA sequence was found to be 71.37% A+T and 28.63% G+C . The CIV genome contains 468 open reading frames (ORFs) . The size of the individual viral gene products ranges between 40 and 2432 amino acids . The analysis of the coding capacity of the CIV genome revealed that 50% (234 ORFs) of all identified ORFs were nonoverlapping . The comparison of the deduced amino acid sequences to entries in protein data banks led to the identification of several genes with significant homologies, such as the two major subunits of the DNA-dependent RNA polymerase, DNA polymerase, protein kinase, thymidine and thymidylate kinase, thymidylate synthase, ribonucleoside-diphosphate reductase, major capsid protein, and others . The highest homologies were detected between putative viral gene products of CIV and lymphocystis disease virus of fish (LCDV) . Although many CIV putative gene products showed significant homologies to the corresponding viral proteins of LCDV, no colinearity was detected when the coding strategies of the CIV and LCDV-1 were compared to each other . An intriguing result was the detection of a viral peptide of 53 amino acid residues (ORF 160L) showing high homology (identity/similarity: 60.0%/30.0%) to sillucin, an antibiotic peptide encoded by Rhizomucor pusillus . Iridovirus homologs of cellular genes possess particular implications for the molecular evolution of large DNA viruses .

Cryobiology, 2001 Mar, 42(2), 121 - 33
Cryopreservation of mouse ovarian tissue following prolonged exposure to an Ischemic environment; Cleary M et al.; In cases in which ovarian tissue is to be cryopreserved for tissue or gene banking it is important to maintain its integrity and viability . This study examined how delays between the death of an animal and the collection/cryopreservation of its ovarian tissue influenced follicle viability . Mouse ovaries were placed in PBS+antibiotic (in vitro) or left within the body (in situ) at room temperature for 0, 3, 6, 12, or 24 h following the death of the donor . These ovaries were cryopreserved at 1 degrees C/min on dry ice or in a -84 degrees C freezer using a passive cooling device or by conventional slow cooling (0.3 degrees C/min) . The ovaries were grafted under the kidney capsule of ovariectomized recipient mice and collected 2 weeks later, and the size and number of follicles were determined . Cryopreserved ovarian tissue grafted immediately after the death of the donor contained numerous viable and healthy follicles independent of the cooling procedure (dry ice, 134 +/- 32; -84 degrees C, 165 +/- 54; slow, 214 +/- 55 follicles per half ovary) . Tissues stored in vitro before cryopreservation retained viable follicles up to 12 h after death (dry ice, 30 +/- 15; -84 degrees C, 86 +/- 45; slow, 93 +/- 33), whereas tissue left in situ had significantly reduced follicle numbers within 3 h of death (dry ice, 36 +/- 12; -84 degrees C, 19 +/- 6; slow, 28 +/- 7) . No significant difference was found between the cooling rates tested, indicating that a passive cooling container which cools at 1 degrees C/min is a suitable alternative to conventional slow cooling . We conclude that ovarian tissues for cryobanking should be cryopreserved as soon as possible after collection or death of the animal to ensure maximal follicular survival.

Cardiovasc J S Afr, 2001 Feb-Mar, 12(1), 42 - 6
Association between Chlamydia pneumoniae and atherosclerotic lesions; Phillips JI et al.; There can no longer be any doubt that viable Chlamydia pneumoniae organisms are present in atherosclerotic lesions . Indeed, the endovascular presence of C . pneumoniae in coronary artery disease (CAD) is common . The fact that this lesion, which is the major cause of stroke, coronary heart disease ( CHD), peripheral vascular disease and aortic aneurysm, can no longer be regarded as sterile has prompted a good deal of study and speculation . Atherosclerotic lesions have been studied in detail, but until recently histological descriptions of the lesion have not included C . pneumoniae organisms . Reviews and analysis of the literature confirm the association between C . pneumoniae and atherosclerotic lesions and CHD . The possibility that C . pneumoniae plays a causal or contributory role in the development of atherosclerotic lesions has been debated . It is of major importance as there is already evidence that antibiotic therapy may be of clinical benefit in patients with CHD . Large clinical trials using antichlamydial agents have been embarked upon which may provide further evidence of a causal role for C . pneumoniae . The underlying mechanism of how C . pneumoniae contributes to lesions and the effect of antibiotic therapy on lesions remain unknown . The association between C . pneumoniae and atherosclerosis is reviewed . Particular attention is paid to the lesion itself and the presence of C . pneumoniae . Potential areas of study that may contribute to this rapidly expanding area of research is explored.

BJU Int, 2001 Jul, 88(1), 72 - 6
Brucellar epididymo-orchitis in Saudi Arabia: a retrospective study of 26 cases and review of the literature; Memish ZA et al.; OBJECTIVE: To review the clinical and laboratory features and response to treatment of patients with acute brucellar epididymo-orchitis reporting to a tertiary care hospital in Riyadh, and to compare these with other cases reported previously . PATIENTS AND METHODS: In this retrospective study, records of all 26 adult patients with brucellosis, who presented with epididymitis or epididymo-orchitis at a tertiary hospital in Riyadh from 1983 to 2000, were reviewed . Positive blood culture or high agglutination titres of > or = 1 : 320 and positive clinical manifestations of brucellosis were the main criteria for diagnosing brucellosis . Among these cases, epididymitis or epididymo-orchitis was diagnosed on the basis of a typical history of gradual onset of scrotal pain and findings of enlarged tender testes and/or epididymis . RESULTS: Epididymo-orchitis occurred in 1.6% of all patients with brucellosis . Most (58%) were 25--44 years old; approximately 77% of the patients presented with acute symptoms of < 2 weeks' duration . All patients complained of swollen painful testicles . Other presenting symptoms included undulant fever (96%), chills (54%) and arthralgia (23%) . Four patients had dysuria and one haematuria . Ten patients gave a positive history of ingestion of raw milk and milk products; one patient had laboratory-acquired brucellosis . Six patients had unilateral epididymo-orchitis (two with features of florid presentation); the remaining 20 had only orchitis (bilateral in two, right in 10 and left in eight) . Leucocytosis was present in six patients; 25 had initial agglutination titres of > 1 : 320 and the remaining patient had a positive blood culture . All patients received combined therapy with streptomycin for the first 2 weeks (or oral rifampicin for 6 weeks) with doxycycline or tetracycline for 6 weeks . All showed improvement, fever subsided in 2--5 days and the scrotal enlargement and tenderness regressed . Only one patient had a relapse within one year . CONCLUSION: In brucellosis-endemic areas, clinicians encountering epididymo-orchitis should consider the likelihood of brucellosis . A careful history, a meticulous physical examination and a rapid laboratory evaluation help in diagnosis . Clinical and serological data are sufficient for diagnosis . Leucocytosis is not an atypical feature of brucellar epididymo-orchitis and so cannot be used for differentiating it from the nonspecific variety . Conservative management with combination antibiotic therapy is adequate for managing brucellar epididymo-orchitis.

Hosp Pract (Off Ed), 2001 Jul 15, 36(7), 49 - 56
Practical management of acute diarrhea; Scheidler MD et al.; A careful history and physical examination are usually enough to assess illness severity, the need for further labortory tests, and often the cause . Supportive treatment generally suffices However, antibiotic or probiotic therapy should be considered in selected patients.

Antisense Nucleic Acid Drug Dev, 2001 Jun, 11(3), 137 - 47
Inhibition of human DNA topoisomerase I by new DNA minor groove ligands: derivatives of oligo-1,3-thiazolecarboxamides; Bugreev DV et al.; A series of novel thiazole-containing oligopeptides (oligo-1,3-thiazolecarboxamides) interesting specifically with the minor groove of DNA was shown to inhibit human DNA topoisomerase I (topo I) . Inhibitory effects of thiazole-containing oligopeptides (TCO) increase with the number of thiazole units in such compounds . Inhibitory properties of TCO containing 3 or 4 thiazole units were shown to be 3-10 times better than those of the well-known natural antibiotic, distamycin A containing pyrrole rings . The structure of various additional groups attached to the N-terminus and C-terminus of TCO had no significant effect on TCO interaction with the complex of DNA and topo I . TCO were shown to be capable of binding with double-stranded DNA (dsDNA), and the majority of TCO analyzed were more effective in binding with dsDNA than distamycin A . Possible reasons for the different effects of distamycin A and TCO on the reaction of relaxation catalyzed by topo I are discussed.

Pharmacotherapy, 2001 Jul, 21(7 Pt 2), 89S - 94S
A controlled trial of a critical pathway for treating community-acquired pneumonia: the CAPITAL study . Community-Acquired Pneumonia Intervention Trial Assessing Levofloxacin; Feagan BG; Recent clinical trials in patients with community-acquired pneumonia (CAP) demonstrated that switching from intravenous to oral antibiotic therapy is safe once clinical improvement is evident, thereby facilitating early hospital discharge . This study evaluated the use of a critical pathway to improve the efficiency of treating CAP in 1743 patients at 19 teaching and community hospitals in Canada . Hospitals were randomized to continue conventional management of CAP (10 hospitals) or implement a critical pathway (9 hospitals) . The main clinical outcome measure was patients' scores (assessed 6 wks after hospital presentation) on the Short-Form 36 Physical Component Summary, a quality-of-life questionnaire . Secondary clinical outcome measures included occurrence of complications, readmission rates, and mortality . The primary economic outcome measure was resource utilization, measured by the number of bed days/patient managed (BDPM) . Clinical outcomes were good in both groups, with no significant differences between the two management strategies . However, use of the clinical pathway was associated with a 1.7-day reduction in BDPM and fewer admissions of low-risk patients.

Pharmacotherapy, 2001 Jul, 21(7 Pt 2), 79S - 82S
Managing antiinfective therapy of community-acquired pneumonia in the hospital setting: focus on switch therapy; Ramirez JA; Targeting patients for early switch from intravenous to oral antibiotic therapy and early hospital discharge is an important strategy in the management of community-acquired pneumonia (CAP) . This strategy can reduce costs due to drug administration and length of hospital stay . We show that switch therapy can be implemented safely when four criteria are met: cough and respiratory distress improve, fever abates for at least 8 hours, white blood cell count is returning to normal, and patient can take drugs orally In prospective clinical studies conducted at our institution, the clinical cure rate with switch therapy was 99%, and mean length of hospital stay was reduced by more than 2 days . Early switch, coupled with hospital discharge, may be possible in nearly half of all CAP patients . Universal use of switch therapy in the United States could result in the total reduction of about 440,000 hospital days annually and an overall savings of $400 million.

J Natl Med Assoc, 2001 Jun, 93(6), 220 - 3
Legionella micdadei lung abscess in a patient with HIV-associated nephropathy; Nzerue C et al.; A patient with end-stage renal disease due to human immunodeficiency-associated nephropathy developed fever, cough and chest pain over a week's duration . He was diagnosed with lung abscess and started on antibiotic coverage . He underwent bronchoscopy because of progression of his illness and persistent fever and bronchoalveolar lavage culture isolated Legionella micdadei . In spite of appropriate antibiotic therapy, the patient remained febrile for 10 days, necessitating chest tube drainage . After a 6-week course of antibiotics and drainage, the patient made an uneventful recovery . Infections due to L . micdadei may be hard to diagnose because of difficulties in isolating this bacteria.

Analyst, 2001 Jun, 126(6), 917 - 22
Determination of naproxen in pharmaceutical preparations by room-temperature phosphorescence . A comparative study of several organized media; Arancibia JA et al.; Different methods for the determination of naproxen by room-temperature phosphorescence (RTP) using organized media such as cyclodextrins (beta-CD and gamma-CD) and micelles (Triton X-100 and sodium dodecyl sulfate) are reported . The inclusion complexes formed between both beta- and gamma-cyclodextrins and naproxen were previously investigated at both acid and basic pH by spectrofluorimetry . In both cases, 1:1 guest-host stoichiometries were established and the corresponding association constants were calculated . Different systems were examined with the purpose of obtaining phosphorescent emission from naproxen solutions, and the best signals were obtained when naproxen was in the presence of beta-CD-cyclohexane-Tl(I), gamma-CD-1,3-dibromopropane, Triton X-100-Tl(I) and SDS-Tl(I), respectively . In all cases, sodium sulfite was used as deoxygenator . The use of an inorganic compound (thallium nitrate) as a heavy-atom source in a cyclodextrin system represents a novel finding . Surface response optimization approaches were carried out to optimize the chemical variables which have an influence on the RTP emission of naproxen . Based on the results obtained, univariate RTP calibration methods for the determination of the analyte in pharmaceutical preparations were satisfactorily developed . In one case, the standard additions method was applied to a mixture of naproxen and the antibiotic tetracycline.

Crit Care Med, 2001 Jul, 29(7), 1350 - 5
Co-amoxiclav pharmacokinetics during posttraumatic hemorrhagic shock; Mimoz O et al.; OBJECTIVE: To determine the effects of severe trauma with hemorrhagic shock on amoxicillin and clavulanate concentrations in plasma and their pharmacokinetics . DESIGN: A prospective, open, descriptive study . SETTING: A 12-bed, adult surgical intensive care unit in a university-affiliated hospital in France . SUBJECTS: Subjects were 12 patients (10 men, 2 women) with severe trauma: median (range) Injury Severity Score, 38 (17-48); Acute Physiology and Chronic Health Evaluation II, 16 (7-38); Simplified Acute Physiology Score II, 41 (23-77) . Also enrolled were 12 healthy volunteers who were matched on age (+/-5 yrs), gender, and body-surface area (+/-20 cm2) . All the trauma patients suffered hemorrhagic shock defined as the association of at least one episode of systolic blood pressure <90 mm Hg and an intravascular volume expansion >2000 mL between trauma and surgery . INTERVENTION: Prophylactic perioperative administration of 2 g of amoxicillin and 0.2 g of clavulanate in combination during the first 12 hrs posttrauma in patients, and at the start of the pharmacokinetic study in volunteers . MEASUREMENTS AND MAIN RESULTS: Serial plasma samples (n = 13) were obtained after the first antibiotic administration to measure antibiotic levels by using high-performance liquid chromatography assays . Compared with volunteers, trauma patients had higher plasma amoxicillin and clavulanate concentrations, attributed to a reduction of the volume of distribution (p =.001 and p =.06, respectively) and, to a lesser extent, of the total body clearance (p =.09 and p =.20, respectively) . Consequently, amoxicillin and clavulanate elimination half-lives were similar for the two groups of subjects . The interindividual variabilities for all the amoxicillin pharmacokinetic parameters were higher in patients . CONCLUSIONS: In trauma patients with hemorrhagic shock requiring surgery, the administration of 2 g of amoxicillin and 0.2 g of clavulanate seems adequate, according to the antibiotic concentrations observed in plasma for both drugs . However, further studies exploring antibiotic concentrations in tissues are warranted.

Lancet, 2001 Jun 30, 357(9274), 2085 - 9
Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on neointima proliferation after coronary stent placement (ISAR-3): a randomised, double-blind, placebo-controlled trial; Neumann F et al.; BACKGROUND: Vascular infection with Chlamydia pneumoniae might boost inflammatory responses that play a pivotal part in neointima formation, which is the main cause of restenosis after stenting . Our aim was to investigate whether or not treatment of C pneumoniae infection with antibiotics prevents restenosis after coronary stent placement . METHODS: We enrolled 1010 consecutive patients with successful coronary stenting into a randomised, double-blind trial . Patients received the macrolide antibiotic roxithromycin 300 mg once daily for 28 days (506), or placebo (504) . Primary endpoint was frequency of restenosis (diameter stenosis >50%) at follow-up angiography, and secondary endpoint was rate of target vessel revascularisation during the year after stenting . A prespecified secondary analysis addressed treatment effect with respect to titre of C pneumoniae in serum . Analysis was by intention to treat . FINDINGS: Rate of angiographic restenosis was 31% (157 lesions) in the roxithromycin group and 29% (148) in the placebo group (relative risk 1.08 {95% CI 0.92-1.26}; p50.43), corresponding to a rate of target vessel revascularisation of 19% (120) and 17% (105), respectively (1.13 {0.95-1.36}; p50.30) . The combined 1-year rates of death and myocardial infarction were 7% (36) in the roxithromycin group and 6% (30) in the placebo group (p50.45) . We showed a significant interaction between treatment and C pneumoniae antibody titre (p50.038 for restenosis, p50.006 for revascularisation), favouring roxithromycin at high titres (adjusted odds ratios at a titre of 1/512 were 0.44 {0.19-1.06} and 0.32 {0.13-0.81}, respectively) . INTERPRETATION: Non-selective use of roxithromycin is inadequate for prevention of restenosis after coronary stenting . There is, however, a differential effect dependent on C pneumoniae titres . In patients with high titres, roxithromycin reduced the rate of restenosis.

J Biomol Struct Dyn, 2001 Jun, 18(6), 858 - 71
Unusual DNA binding exhibited by synthetic distamycin analogues lacking the N-terminal amide unit under high salt conditions; Thomas M et al.; The binding of three analogues of the minor-groove binding antiviral antibiotic distamycin (Dst) with double-stranded (ds)-DNA were monitored using ds-DNA melting temperature (Tm) measurements, ethidium bromide (EtBr) displacement assay, footprinting analysis and induced circular dichroism (ICD) . These compounds contained 3-5 N-methyl-pyrrole-carboxamide units and lacked the N-terminal formamide unit present in Dst . These experiments suggested that the present analogues did not compromise their AT-specificity despite the deletion of the N-terminal formamide unit . The binding affinities, however, were significantly affected . Interestingly, the analogue with three N-methyl-pyrrole-carboxamide units exhibited an initial decrease in ICD at > 40 mM salt concentrations . This was followed by a pronounced recovery of ICD at > 1.6 M salt concentrations, a phenomenon hitherto not observed with any other DNA binding molecules . The pentapyrrole analogue exhibited the highest binding affinity with CT-DNA under normal (40 mM) salt conditions . However, it suffered maximum relative dissociation under high salt conditions and did not exhibit any recovery in ICD at higher NaCl concentrations . The analogues possessing four and five pyrrole rings exhibited intense ICD signals with poly d(GC) in the ligand absorption region in the presence of 40 mM NaCl, unlike the one with three pyrrole rings . These ICD signals were however, highly susceptible to changes in ionic strength . Thus subtle modifications in the ligand molecular structure can have dramatic effect on their DNA binding properties.

J Vet Pharmacol Ther, 2001 Jun, 24(3), 193 - 7
Allometric analysis of thiamphenicol disposition among seven mammalian species; Castells G et al.; The pharmacokinetics of thiamphenicol (TAP), a broad-spectrum antibiotic, was determined in male mice, rats, rabbits, dogs, pigs, sheep and calves . The relationship between the main pharmacokinetic parameters of TAP and body weight (W) was studied across these seven mammalian species, using double-logarithmic plots . The experimental values of volume of distribution (Vss), clearance (Cl) and elimination half-life (t(1/2)beta) were plotted, and extrapolated values were determined from corresponding allometric equations . These parameters were fitted to the following equations: Vss=0.98W0.92, Cl=15.80W0.76 and t(1/2)beta=0.94W0.20, and present good correlation (Vss: r2=0.997, P < 0.001; Cl: r2=0.976, P < 0.001, t(1/2)beta: r2=0.852, P < 0.005), that is expected of a drug eliminated primarily by renal glomerular filtration, with insignificant hepatic metabolism . For the t(1/2)beta, the extrapolated and observed values were similar . The extrapolated values of Cl were close to the experimental values, except for the mouse and pig mean percent error {(M.E.) equal to 62 and 119%, respectively}, while the extrapolated and observed values for the Vss were very similar . The comparison between experimental and extrapolated values suggests that it could be possible to extrapolate, with good prediction, the kinetic parameters of this drug for mammalian species, using allometric scaling, except for the species that eliminate the drug by a combination of renal excretion and hepatic metabolism.

Shock, 2001 Jul, 16(1), 59 - 63
The role of bacterial translocation on neutrophil activation during hemorrhagic shock in rats; Shimizu T et al.; Some biological responses to hemorrhage have been reported to be associated with bacterial translocation (BT) . While the relationship between peripheral blood neutrophils and BT in the late phase of hemorrhagic shock or burn injury has been reported, this relationship in the early phase has not been fully elucidated . We investigate the role of BT in neutrophil activation and priming during hemorrhagic shock . The experimental rats were divided into three groups: a group with normal intestinal flora (NF group), an antibiotic-decontaminated group (AD group), and a sham shock group with normal intestinal flora (sham group) . Hemorrhagic shock was induced in the NF and AD groups (MAP 30 mm Hg for 30-90 min) . The rats were sacrificed at 30, 60, or 90 min following the shock induction . Cultures were taken from the liver, spleen, mesenteric lymph nodes (MLNs), and systemic blood to assess the occurrence of BT . Hydrogen peroxide generation and CD11b/c expression were assayed by flow cytometry to evaluate peripheral blood neutrophil activation and priming, respectively . In the NF group, significant BT to the MLNs and spleen was noted from 30 min after the shock induction, and significant hydrogen peroxide generation was also noted from 30 min . The expression of CD11b/c on neutrophils was significantly up-regulated at 90 min after the shock induction . Furthermore, BT, as also the aforementioned parameters of neutrophil function, was significantly suppressed in the AD group . We, therefore, concluded that neutrophil activation and priming during hemorrhagic shock might be closely related to BT, and that infectious factors possibly influence the host responses starting from the early phase of damage, even in noninfectious stress-inducing conditions.

J Glaucoma, 2001 Jun, 10(3), 211 - 4
Topical verapamil in glaucoma filtration surgery; Shin DH et al.; PURPOSE: Because of the reported antifibroblastic effect of verapamil, a calcium-channel blocker, we investigated the potential benefit of adjunctive topical verapamil in patients undergoing glaucoma filtration surgery . METHODS: This prospective, double-masked, randomized study included 56 eyes of 56 consecutive patients with chronic open-angle glaucoma undergoing trabeculectomy (primary or surgical revision of failed trabeculectomy), trabeculectomy combined with cataract surgery, or Molteno drainage device implantation . Postoperatively, the treated eyes received verapamil (0.25%) or one drop of placebo four times a day for 1 month in addition to 1% prednisolone four times a day and corticosteroid-antibiotic ophthalmic ointment at bedtime . RESULTS: There were no significant differences in preoperative mean intraocular pressure, mean number of medications, and glaucoma severity between the verapamil and placebo groups . There were also no significant differences between the two groups in filtration success rate, mean intraocular pressure, and mean number of medications on postoperative days 1, 4, or 7 and at postoperative months 1, 2, 3, 4, 5, and 6 (P > 0.05) . CONCLUSION: There was no significant benefit of adjunctive topical verapamil when it was used after trabeculectomy, trabeculectomy combined with cataract surgery, or Molteno drainage device implantation.

Poult Sci, 2001 Jun, 80(6), 718 - 23
The effect of mannanoligosaccharides, bambermycins, and virginiamycin on performance of large white male market turkeys; Parks CW et al.; A study was conducted to evaluate the effects of mannanoligosaccharides (MOS), bambermycins (BAM), and virginiamycin (VIR) on the growth performance of male turkeys . Hybrid Large White male poults were assigned to six dietary treatments: control, MOS, BAM, VIR, MOS+BAM (MB), and MOS+VIR (MV) . All diets were formulated to meet NRC (1994) nutrient requirements . There were eight replicate floor pens per treatment with 20 birds per pen reared from 1 to 140 d . Body weight and feed conversion (FC) were collected at 3-wk intervals and at 20 wk of age . Mortality and culled birds were recorded daily . All treatments except MV significantly (P < 0.05) increased 20 wk BW . Body weight was increased at 12 wk by BAM, whereas VIR increased BW at Weeks 12 and 15 . All treatments improved FC for Weeks 0 to 3, whereas VIR, MB, and MV improved FC for Weeks 0 to 12 and 0 to 18 . There were no treatment effects on cumulative mortality or cull rate . Dietary supplemental MOS, BAM, and VIR resulted in improved growth performance of Large White turkeys . These results indicate that MOS may be utilized as an alternative to antibiotic growth promotants to improve turkey performance.

Ther Umsch, 2001 Jun, 58(6), 381 - 6
{Travel medicine for HIV-infected patients}; Rossi M et al.; Many HIV-infected persons travel from temperate zones to (sub)tropical destinations . HIV-specific immigration issues, medical resources abroad and problems regarding travelling with multiple medications have to be anticipated . When prescribing immunizations and specific chemoprophylaxis, the stage of immunodeficiency as well as drug interactions with antiretrovirals and medicaments against opportunistic infections have to be taken into account . Live vaccines may be contraindicated . Immunocompromised HIV-infected travellers have a higher risk for serious courses of diseases by enteropathogens . Therefore a good information about food hygiene is important and a prescription of an antibiotic to take in case of severe diarrhea may be indicated . A new antiretroviral combination therapy should not be started immediately before travelling to the tropics . The possibility to continue an established HIV treatment during travel has to be evaluated cautiously . With good pre-travel advice the risk of severe health problems is low for most HIV-infected travellers.

Ther Umsch, 2001 Jun, 58(6), 376 - 80
{First aid kit for travelers}; Markwalder K; The first aid kit for travellers is essentially thought to permit symptomatic self-treatment of common and mostly trivial health problems abroad . If professional medical assistance is likely not to be accessible a few additional items--e.g . an antibiotic--must be considered . The indications and proper handling of any medication which requires a physician's prescription have to be carefully explained to its potential user . The decision as to recommend drugs other than those in the basic first aid kit must take into account not only the risk of particular diseases but also the ability of the traveller to applicate a drug in the correct way for defined indications.

Neurosurgery, 2001 Jul, 49(1), 65 - 8; discussion 69-70
C1-C2 transarticular screw fixation for atlantoaxial instability: a 6-year experience; Haid RW Jr et al.; OBJECTIVE: We review a 6-year, single-center experience using the technique of C1-C2 transarticular screw fixation for atlantoaxial instability in 75 consecutive operations . METHODS: The study group was composed of 43 men and 32 women, with a mean age of 44 years (range, 8-76 yr) . Each patient had documented atlantoaxial instability . In 28 patients (37%), atlantoaxial instability was a result of trauma; in 22 patients, (29%), it was a result of rheumatoid arthritis; in 16 patients (21%), it was a result of prior surgery; and in 9 patients (12%), it was a result of congenital abnormalities . All patients underwent stabilization with C1-C2 transfacetal screws and a posterior interspinous construct . Nine patients had unilateral screws placed . Postoperatively, the patients were maintained in a rigid cervical orthosis for a mean of 11 weeks (range, 8-15 wk); five patients were immobilized with halo fixation for a mean of 13 weeks (range, 10-16 wk) . The mean follow-up period was 2.4 years (range, 1-5.5 yr) . RESULTS: Osseous fusion was documented in 72 patients (96%) . There were no hardware failures; however, three patients developed pseudarthrosis . Two superficial wound infections (one at the graft site and one at the cervical incision site) required antibiotic therapy . Four patients had transient suboccipital hypesthesia . No instances of an errant screw, dural laceration, or injury to the vertebral artery, spinal cord, or hypoglossal nerve were noted . CONCLUSION: C1-C2 transarticular screw fixation supplemented with an interspinous construct yielded a 96% fusion rate, with a low incidence of complications . We attribute our successful outcomes to careful preoperative assessment and meticulous surgical technique.

Ir Med J, 2001 Apr, 94(4), 117 - 8
Sigmoid sinus thrombosis: an old foe revisited; Keogh IJ et al.; Sigmoid sinus thrombosis (SST) has become increasingly uncommon . In the pre-antibiotic era this condition had a mortality rate of over 90%.1 A high index of suspicion is required to make the diagnosis . We present a rare case of sigmoid sinus thrombosis secondary to mastoiditis, which illustrates the problems of delayed diagnosis . This report highlights the importance of rapid diagnosis and early surgical intervention . We emphasis the need for scanning and otolaryngology referral in all cases of middle ear disease associated with pain or vertigo which does not resolve rapidly on appropriate antibiotic therapy.

Bone Marrow Transplant, 2001 May, 27 Suppl 2, S23 - 9
Mobilization of peripheral blood stem cells following myelosuppressive chemotherapy: a randomized comparison of filgrastim, sargramostim, or sequential sargramostim and filgrastim; Weaver CH et al.; Myelosuppressive chemotherapy is frequently used for mobilization of autologous CD34(+) progenitor cells into the peripheral blood for subsequent collection and support of high-dose chemotherapy . The administration of myelosuppressive chemotherapy is typically followed by a myeloid growth factor and is associated with variable CD34 cell yields and morbidity . The two most commonly used myeloid growth factors for facilitation of CD34 cell harvests are granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) . We performed a randomized phase III clinical trial comparing G-CSF, GM-CSF, and sequential administration of GM-CSF and G-CSF following administration of myelosuppressive chemotherapy . We evaluated CD34 yields, morbidity, and cost-effectiveness of the three cytokine schedules . One hundred and fifty-six patients with multiple myeloma, breast cancer, or lymphoma received cyclophosphamide with either paclitaxel or etoposide and were randomized to receive G-CSF 6 microg/kg/day s.c., GM-CSF 250 microg/m(2)/day s.c., or GM-CSF for 6 days followed by G-CSF until completion of the stem cell harvest . Compared with patients who received GM-CSF, patients who received G-CSF had faster recovery of absolute neutrophil count to 0.5 x 10(9) per liter (median of 11 vs14 days, P = 0.0001) with fewer patients requiring red blood cell transfusions (P= 0.008); fewer patients with fever (18% vs 52%, P = 0.001); fewer hospital admissions (20% vs 42%, P = 0.13); and less intravenous antibiotic therapy (24% vs 59%, P = 0.001) . Patients who received G-CSF also yielded more CD34 cells (median 7.1 vs 2.0 x 10(6) kg per apheresis, P = 0.0001) and a higher percentage achieved 2.5 x 10(6) CD34 cells per kilogram (94% vs 78%, P = 0.21) and 5 x 10(6) CD34 cells per kilogram (88% vs 53%, P = 0.01) or more CD34 cells per kilogram with fewer aphereses (median 2 vs 3, P = 0.002) and fewer days of growth factor treatment (median 12 vs 14, P = 0.0001) . There were no significant differences in outcomes between groups receiving G-CSF alone and the sequential regimen . After high-dose chemotherapy, patients who had peripheral blood stem cells mobilized with G-CSF or the sequential regimen received higher numbers of CD34 cells and had faster platelet recovery with fewer patients requiring platelet transfusions than patients receiving peripheral blood stem cells mobilized by GM-CSF . In summary, G-CSF alone is superior to GM-CSF alone for the mobilization of CD34(+) cells and reduction of toxicities following myelosuppressive chemotherapy . An economic analysis evaluating the cost-effectiveness of these three effective schedules is ongoing at the time of this writing.

Eur J Gastroenterol Hepatol, 2001 Jun, 13(6), 737 - 9
Ornidazole-induced autoimmune hepatitis; Kosar Y et al.; Ornidazole is a commonly prescribed antiparasitic drug for parasitic infestations, including amoebiasis, giardiasis and Trichomonas vaginalis . Several cases of antibiotic-induced autoimmune hepatitis (AIH) or AIH-like syndrome have been reported recently . In this report, we describe a 35-year-old woman with two relapses of AIH induced by ornidazole prescribed for diarrhoea and vaginal infection.

J Pediatr Surg, 2001 Jul, 36(7), 1008 - 11
A prospective study of a one-week nonbismuth quadruple therapy for childhood Helicobacter pylori infection; Chan KL et al.; PURPOSE: In the eradication of Helicobacter pylori infection, a 1-week therapy improves patient compliance, but drug resistance may limit its efficacy . The effectiveness of the 1-week nonbismuth quadruple therapy was studied prospectively in children with proven H pylori infection in a population with a high rate of metronidazole resistance . METHODS: All pediatric patients who presented to our institutions with acute and chronic upper gastrointestinal conditions requiring endoscopy from June 1997 to February 2000 were investigated prospectively for H pylori infection . Gastric biopsy specimens were analyzed with rapid urease test and histopathology, H pylori-positive children were treated with omeprazole, clarithromycin, amoxicillin, and metronidazole for 7 days . The result of treatment was assessed 1 month after treatment with endoscopy and biopsy . The same treatment was repeated for 2 weeks if H pylori was still present . In patients who needed a third endoscopy, their biopsy specimens were cultured to determine antibiotic sensitivity . Results were correlated with patients' symptoms and endoscopic findings . RESULTS: Thirty-three children with acute (severe epigastric pain, n = 14; gastrointestinal bleeding, n = 9) and chronic (recurrent abdominal pain, n = 7; anemia, n = 3) conditions were treated for H pylori . Thirty-one (94%) were confirmed to have H pylori eradicated by a 1-week therapy, whereas 1 patient had eradication after a further 2-we'ek therapy (3.3%) . The only unresponsive patient had H pylori resistant to both clarithromycin and metronidazole . All ulcers and erosions healed after the eradication of H pylori . Three patients had persistent recurrent abdominal pain despite H pylori eradication . CONCLUSIONS: The 1-week therapy with omeprazole, clarithromycin, amoxicillin, and metronidazole is an effective treatment of H pylori in children in a population with a high incidence of metronidazole resistant strain of H pylori . Peptic ulcers and erosions healed with the eradication of the bacteria .

Int Immunol, 2001 Jul, 13(7), 921 - 31
Tetracyclines inhibit activated B cell function; Kuzin II et al.; Tetracyclines have recently been shown to exert a number of pleiotropic anti-inflammatory and immunomodulatory activities, independent of their antibiotic properties . These include the ability to inhibit metalloproteinases (MP), a class of enzymes involved in crucial cellular functions such as the shedding of soluble mediators and their receptors from the cell surface, as well as interaction with, and remodeling of, the extracellular matrix . Here we report that doxycycline at therapeutic concentrations (1--5 microg/ml) significantly suppresses Ig secretion and class switching by in vitro activated murine B cells . Suppression of Ig secretion correlates with a decrease in levels of mRNA for the terminal B cell differentiation-associated genes Blimp-1 and mad-4, as well as to a reduction in expression of the plasma cell markers Syndecan-1 and J chain . Inhibition of class switching occurs at the recombination stage and is also induced by other MP inhibitors, including tetracycline analogs lacking antibiotic activity and the chemically unrelated hydroxamate KB8301 . These novel, direct effects of MP inhibitors on B lymphocytes suggest an intrinsic role for MP in B cell activation and likely explain some of the observed in vivo immunomodulatory properties of tetracyclines . Moreover, these findings have significant implications for tetracycline therapy in Ig-mediated autoimmune or allergic diseases and raise questions about the use of doxycycline-inducible transgenic systems for the study of B cell function.

Neuron, 2001 Jun, 30(3), 665 - 76
Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice; Cherny RA et al.; Inhibition of neocortical beta-amyloid (Abeta) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD) . Cu and Zn are enriched in Abeta deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro . Here we report a 49% decrease in brain Abeta deposition (-375 microg/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator . This was accompanied by a modest increase in soluble Abeta (1.45% of total cerebral Abeta); APP, synaptophysin, and GFAP levels were unaffected . General health and body weight parameters were significantly more stable in the treated animals . These results support targeting the interactions of Cu and Zn with Abeta as a novel therapy for the prevention and treatment of AD.

Compr Ther, 2001 Summer, 27(2), 104 - 7
Surgery and the patient with arthritis; Rothschild BM; Patients with rheumatologic disease (e.g., arthritis) require special attention when surgery is considered . Proactive attention to medication usage, corticosteroid coverage, airway, respiratory, joint stability and fragility challenges, cold exposure, and coagulation risks facilitate surgical intervention for such individuals.

Biophys Chem, 2001 Jul 2, 91(2), 125 - 33
The interactions of amphotericin B with various sterols in relation to its possible use in anticancer therapy; Charbonneau C et al.; Amphotericin B (AmB) is still the most common anti-fungal agent used to treat systemic fungal infections . It is known that this antibiotic acts by forming pores with the ergosterol contained in the membranes of fungi, but it also interacts with the cholesterol contained in the membranes of eukaryotic cells, hence its toxicity . AmB may also interact with the most common oxidation products of cholesterol found in vivo, together with interacting with biosynthetic precursors of cholesterol, namely, lanosterol and 7-dehydrocholesterol (7-DHC) . The purpose of the present work was to study the interactions in solution between AmB and these various sterols, the techniques used being UV-Vis spectroscopy and differential scanning calorimetry . The results are globally interpreted in terms of the structural differences between the sterols . We show that AmB selectively interacts with 7-DHC which, according to a recent hypothesis proposed in the literature, has been identified in connexion with a therapeutic strategy against hepatocellular carcinomas . We find that the affinity of AmB towards 7-DHC is even greater than the affinity of the antibiotic towards ergosterol . We also find that AmB selectively interacts with the principal oxidation product of cholesterol, 7-ketocholesterol, a situation that has to be taken into account when AmB is administered.

Transpl Infect Dis, 2001 Mar, 3(1), 8 - 15
Patterns of cytomegalovirus infection in simultaneous kidney-pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and prednisone with ganciclovir prophylaxis; Lo A et al.; BACKGROUND: The impact of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroid immunosuppression on cytomegalovirus (CMV) infection in combination with ganciclovir prophylaxis in simultaneous kidney-pancreas transplantation (SKPT) has not been well studied . METHODS: A retrospective analysis was made of 75 SKPTs performed between 1 January 1996 and 7 January 1999 . All patients received ganciclovir for 3 months, but CMV donor (D)+ / recipient (R)- patients received ganciclovir for 6 months . RESULTS: 16/74 (22%) were CMV D+/R-, 25 (33%) D+/R+, 16 (22%) D-/R+, and 17 (23%) D-/R- (1 patient with unknown donor serology was excluded) . The mean time to CMV infection was 198 days post-transplant . The incidence of either CMV infection or tissue invasive CMV disease was 16/74 (22%), including 9 (12%) with CMV infection and 7 (10%) CMV disease . The one-year patient, kidney, and pancreas graft survival rates were 91%, 89%, and 83%, respectively . The mean follow-up was 29 months (minimum of 12 months) . CMV infection was not associated with an increased incidence of graft failure or mortality . The D+/R- group had the highest incidence of CMV infection (44%) compared with the other serologic groups (17%, P=0.02) . Concurrent CMV and rejection occurred more frequently in the D+/R- than the other serologic groups (25% vs . 7%, P=0.03) . The D-/R- group had the best outcomes, with no CMV infection, improved kidney graft survival at the end of follow-up (82% vs . 72%, P=0.04) and the highest event-free survival (no CMV infection, rejection, or graft loss) when compared to the other groups (76% vs . 33%, P<0.01) . CONCLUSIONS: Compared to previous studies, ganciclovir prophylaxis delayed the onset and reduced the severity of CMV infection in patients receiving TAC, MMF, and steroids . Despite ganciclovir prophylaxis, CMV seronegative patients receiving CMV D+ organs had worse outcomes than seronegative recipients receiving CMV D- organs.

Surg Today, 2001, 31(6), 553 - 6
Fournier's gangrene: report of six cases; Ochiai T et al.; Fournier's gangrene (FG) is a fatal infectious disease with necrotic fasciitis of the external genitalia . This disease persists to this day in spite of recent advances in antibiotics . Although fewer than 100 cases have been reported in Japan, we have treated six cases in the last 4 years . The patients consisted of five men and one woman, with an average age of 47.5 years . All patients received surgical treatment including incisions, aggressive debridement, drainage, irrigation, and antibiotic therapy . Two patients, who suffered from underlying diseases of diabetic nephropathy and inclusion body myositis, died . These findings confirm the fact that FG requires a prompt diagnosis and immediate surgical treatment.

Surg Today, 2001, 31(6), 502 - 6
The effects of cefephim, G-CSF, and sucralfate on bacterial translocation in experimentally induced acute pancreatitis; Colak T et al.; The preventive effects of granulocyte colony-stimulating factor, cefephim, and sucralfate on bacterial translocation in experimentally induced acute pancreatitis were investigated . Forty male Wistar albino rats were used in this study . For each rat, the pancreatobiliary ductus was ligated and hence acute pancreatitis was induced . In the control group, no further procedure was performed . Meanwhile, cefephim as an antibiotic, filgrastim, which is a colony-stimulating factor, and sucralfate were given to the other groups at the specified doses . To inhibit bacterial translocation by preserving the bowel barrier, sucralfate, which is known to have a cytoprotective effect on the gastrointestinal system, was used in high doses . Cefephim 30 mg/kg per day (intramuscularly) in group II, filgrastim 10 mg/kg per day (subcutaneously) in group III, and sucralfate 50 mg/kg per day by 8-F feeding tube gavage into the stomach in group IV were given . The number of bacteria translocated into the mesenteric lymph nodes, pancreas, liver, and spleen in the control group significantly increased in comparison with the other groups (P < 0.05) . The average number of leukocytes (per mm3) in the control group was significantly higher than that of other groups (P < 0.0001) . Regarding the average serum amylase levels, the values of all groups clearly decreased in comparison with the control group (P < 0.0001) . Although in the cefephim, filgrastim, and sucralfate groups, (+) pancreatitis was generally seen, in the control group (+++) pancreatitis was detected . Bacterial translocation to the mesenteric lymph nodes and pancreas was partially prevented by filgrastim and sucralfate, and was completely prevented by cefephim . We conclude that in the management of acute pancreatitis, the use of the prophylactic antibiotics, sucralfate and filgrastim, may be advantageous.

Org Lett, 2001 Feb 8, 3(3), 449 - 51
Exploiting the reversibility of olefin metathesis . Syntheses of macrocyclic trisubstituted alkenes and (R,R)-(-)-pyrenophorin; Furstner A et al.; {figure: see text} The formation of the trisubstituted cycloalkene 7 by RCM of diene 5 proceeds via the acyclic dimer 6, thus demonstrating the ready reversibility of olefin metathesis if catalyzed by "second generation" ruthenium carbene complexes such as 2-4 . When applied to acrylate 11, these catalysts trigger a cyclooligomerization process that evolves with time and serves as key step en route to the lactide antibiotic (-)-pyrenophorin 8.

Biotechnol Bioeng, 2001 Sep 5, 74(5), 376 - 88
Assessment of near-infrared spectral information for rapid monitoring of bioprocess quality; Vaidyanathan S et al.; Access to real-time process information is desirable for consistent and efficient operation of bioprocesses . Near-infrared spectroscopy (NIRS) is known to have potential for providing real-time information on the quantitative levels of important bioprocess variables . However, given the fact that a typical NIR spectrum encompasses information regarding almost all the constituents of the sample matrix, there are few case studies that have investigated the spectral details for applications in bioprocess quality assessment or qualitative bioprocess monitoring . Such information would be invaluable in providing operator-level assistance on the progress of a bioprocess in industrial-scale productions . We investigated this aspect and report the results of our investigation . Near-infrared spectral information derived from scanning unprocessed culture fluid (broth) samples from a complex antibiotic production process was assessed for a data set that incorporated bioprocess variations . Principal component analysis was applied to the spectral data and the loadings and scores of the principal components studied . Changes in the spectral information that corresponded to variations in the bioprocess could be deciphered . Despite the complexity of the matrix, near-infrared spectra of the culture broth are shown to have valuable information that can be deconvoluted with the help of factor analysis techniques such as principal component analysis (PCA) . Although complex to interpret, the loadings and score plots are shown to offer potential in process diagnosis that could be of value in the rapid assessment of process quality, and in data assessment prior to quantitative model development .

Proc Natl Acad Sci U S A, 2001 Jul 3, 98(14), 7712 - 7 Epub 2001 Jun 26.
In vitro characterization of DNA gyrase inhibition by microcin B17 analogs with altered bisheterocyclic sites; Zamble DB et al.; Microcin B17 (MccB17) is a 3.1-kDa Escherichia coli antibiotic that contains thiazole and oxazole heterocycles in a peptide backbone . MccB17 inhibits its cellular target, DNA gyrase, by trapping the enzyme in a complex that is covalently bound to double-strand cleaved DNA, in a manner similar to the well-known quinolone drugs . The identification of gyrase as the target of MccB17 provides an opportunity to analyze the relationship between the structure of this unusual antibiotic and its activity . In this report, steady-state parameters are used to describe the induction of the cleavable complex by MccB17 analogs containing modified bisheterocyclic sites . The relative potency of these analogs corresponds to the capacity of the compounds to prevent growth of sensitive cells . In contrast to previously reported experiments, inhibition of DNA gyrase supercoiling activity by wild-type MccB17 also was observed . These results suggest that DNA gyrase is the main intracellular target of MccB17 . This study probes the structure-function relationship of a new class of gyrase inhibitors and demonstrates that these techniques could be used to analyze compounds in the search for clinically useful antibiotics that block DNA gyrase.

Leuk Lymphoma, 2001 Feb, 40(5-6), 491 - 8
Resveratrol--from the bottle to the bedside?
Pervaiz S.
Resveratrol, a naturally occurring plant antibiotic has been the focus of a number of studies investigating its biological attributes, which include anti-oxidant activity, anti-platelet aggregation effect, anti-atherogenic property, estrogen-like growth promoting effect, growth inhibiting activity, immunomodulation, and chemoprevention . More recently, since the first report on the apoptosis inducing activity of resveratrol in human cancer cells, the interest in this molecule as a potential chemotherapy agent has significantly intensified . Not only has its role as an anti-cancer agent been corroborated, but the precise mechanism(s) of the anti-cancer activity of resveratrol is/are being elucidated . Our group has been active in studying the cross talk between the caspase family of proteases and mitochondria, in drug-induced apoptosis . In this regard, we have shown that the cancer preventive activity of resveratrol could be attributed to its ability to trigger apoptosis in human leukemia and breast carcinoma cells . The cytotoxicity of resveratrol is restricted against these transformed cell types due to its ability to selectively upregulate CD95-CD95L interaction on the tumor cell surface, unlike normal peripheral blood cells . Despite the involvement of the CD95 signaling pathway, apoptosis induced by resveratrol is not accompanied by robust caspase 8 activation, but involves mitochondrial release of cytochrome C and downstream activation of caspases 9 and 3 . We also extrapolate these in vitro findings in a murine model of carcinogensis, and demonstrate in vivo induction of apoptosis in mouse skin papillomas . These findings highlight the chemotherapeutic potential of this polyphenolic compound.

Am J Surg, 2001 Feb, 181(2), 177 - 86
Clinical course, treatment, and multivariate analysis of risk factors for pyogenic liver abscess; Alvarez Perez JA et al.; BACKGROUND: Pyogenic liver abscess is a threatening condition . The purpose of this study was to audit the clinical behavior and to analyze the risk factors . METHODS: One hundred and thirty-three patients treated in five hospitals during the years 1985 to 1997 were studied . By univariate and multivariate analysis we tried to identify any risk factor associated with complicated clinical course and complicated-related clinical course, and with hospital mortality . RESULTS: Sixty-three patients (47%) were subjected to a percutaneous drainage, 45 (34%) were treated by open surgical drainage, and the remaining 25 cases (19%) received antibiotic therapy alone . Prognostic variables for a complicated clinical course were the presence of shock, low hemoglobin level, elevated prothrombin time, and polymicrobial infection . Shock, distress, low hemoglobin level, increased creatinine, and positive blood culture were significant predictors of a complicated-related clinical course . Concerning mortality, a biliary origin, shock, multiple abscesses, low hemoglobin level, and high concentration of blood urea nitrogen were independent predictors . CONCLUSIONS: Treatment of pyogenic liver abscesses should be tailored to each patient, however, the majority of them can be successfully treated with antibiotics and percutaneous methods . Those with signs of organ failure or septicemia should preferably be managed in the intensive care unit.

Hosp Case Manag, 2001 Jul, 9(7), 100 - 2, 98
Standardized treatment cuts pneumonia deaths; Manifestations of tick-borne illness . Incidence and variety are increasing worldwide; National Naval Medical Center, Infectious Diseases, Bldg 9, Room 1633, 8901 Wisconsin Ave, Bethesda, MD 20889-5600, USA . chargoodman@worldnet.att.net

The incidence and variety of diseases associated with tick bites have continued to grow worldwide . Lyme disease, the most common tick-borne disease in the United States, has received extensive media coverage because of its protean manifestations and propensity for causing chronic disease . Our ability to prevent, identify, and effectively treat Lyme disease and other tick-borne diseases has significantly improved in the last decade . Tick-borne illnesses should be one of the differential diagnostic considerations in patients with consistent clinical findings and exposure history . In addition, the prudent use of laboratory testing ensures an accurate diagnosis while avoiding the cost and risk of inappropriate diagnostic tests and antibiotic therapy.

J Ind Microbiol Biotechnol, 1999 Oct, 23(4-5), 252 - 260
Detection of Sphingomonas spp in soil by PCR and sphingolipid biomarker analysis; Leung KT et al.; Sphingomonas spp possess unique abilities to degrade refractory contaminants and are found ubiquitously in the environment . We developed Sphingomonas genus-specific PCR primers (SPf-190 and SPr1-852) which showed specific amplification of a 627-bp 16S rDNA fragment from Sphingomonas spp . A PCR assay using these Sphingomonas specific primers was developed to detect Sphingomonas aromaticivorans B0695R in three texturally distinct soil types, showing detection limits between 1.3-2.2 x 10(3) CFU g(-1) dry soil . A sphingolipid extraction protocol was also developed to monitor Sphingomonas populations in soil quantitatively . The detection limit of the assay was 20 pmol g(-1) dry soil, equivalent to about 3 x 10(5) cells g(-1) dry soil . Survival of S . aromaticivorans B0695R was monitored in the three different soils by antibiotic selective plate counting, PCR and sphingolipid analysis . All three approaches showed that the B0695R cells persisted in the low biomass Sequatchie sub-soil at about 3-5 x 10(7)cells g(-1) dry soil . In comparison to the plate counting assay, both the PCR and sphingolipid analysis detected a significantly higher level of B0695R cells in the clay soil and Sequatchie top-soil, indicating the possibility of the presence of viable but non-culturable B0695R cells in the soils . The combination of PCR and sphingolipid analysis may provide a more realistic estimation of Sphingomonas population in the environment.

Eur J Cardiothorac Surg, 2001 Jul, 20(1), 19 - 23, discussion 23-4
Surgery for bronchiectasis; Prieto D et al.; OBJECTIVE: The incidence of bronchiectasis has declined markedly in developed countries . However, a reasonable number of patients still need surgery, despite aggressive physiotherapy and antibiotic therapy . We have reviewed our patients to clarify the benefits from surgery and to analyse the complications . MATERIAL AND METHODS: Between 1988 and 1999, we have operated on 119 patients with bronchiectasis, 71 female and 48 male, with a mean age of 42.2 years (range 11--77 years) . Surgery was indicated because of unsuccessful medical therapy in 66 patients (55%), 31 (26%) had haemoptysis, 11 (9.2%) had lung abscess, 10 (8.4%) had lung masses, and three (2.5%) had pneumothorax . The most common manifestations were cough with sputum in 90 patients (76%), haemoptysis in 45 (38%) and recurrent infections in 57 (48%) . The mean duration of the symptoms was 4 years (range 1--40 years) . The lower lobes were diseased in 61 patients and bilateral disease was found in ten . The mean number of involved pulmonary segments was five (range 1-15) . A lobectomy was performed in 75 patients (62%), a segmentectomy in 12 (10%), a pneumonectomy in nine (7.4%) and a bilobectomy in four (3.3%) . Complete resection of the disease was achieved in 108 cases (91%) . RESULTS: There was no operative mortality and perioperative morbidity occurred in 15 patients (15%), including temporary broncho-pleural fistulae in 7 (5.8%), and post-operative haemorrhage and atrial arrhythmias in four (3.3%) each . After a mean follow-up was 4.5 years, 73 patients (68%) of this group were asymptomatic, and 31 (29%) had meaningful clinical improvement, while only four (3.7%) maintained or worsened prior symptoms . The best clinical improvement occurred in patients with complete resection of the disease (P=0.008) . There were no differences in the respiratory function, comparing pre- and post-operative data, with a 2-year of minimum interval . The VC was 91 and 89% and the FEV1 was 83% and 81% of expected, respectively before and after surgery, (P=NS) . CONCLUSION: Surgery of pulmonary bronchiectasis has few complications and markedly improves symptoms in the great majority of patients, especially when complete resection of the disease is achieved . Pulmonary resection of bronchiectasis does not alter respiratory function.

Liver, 2001 Jun, 21(3), 217 - 22
Concomitant inflammatory pseudotumor of the liver and spleen; Di Vita G et al.; We report the case of a 53-year-old man with inflammatory pseudotumor (IPT) of the liver and spleen . This concomitant association has rarely been reported . The patient presented with a hypoechoic mass in the liver and a clinical picture of recurrent sepsis; hematochemical exams and imaging data were nonspecific . Antibiotic therapy improved the clinical course, but did not resolve it definitively . After 50 days of therapy, as the hepatic mass decreased a similar lesion appeared in the spleen . The final diagnosis was made on splenectomy and an intra-operative biopsy of the residual liver lesion . The diagnostic problems encountered in this very rare association of IPT of the liver and spleen were similar to those for isolated IPT in the respective single organ sites . After 15 months of follow-up, the patient is in good health and no recurrence of symptoms or masses has been observed.

Clin Microbiol Infect, 2001 Apr, 7(4), 187 - 92
Polycolonization of Helicobacter pylori among Chinese subjects; Yakoob J et al.; OBJECTIVE: To investigate the situation among Chinese patients with regard to infection with multiple strains of Helicobacter pylori . METHODS: Biopsy specimens for culture of H . pylori were obtained from gastric antrum, body and fundus of 20 patients during endoscopic investigation of upper gastrointestinal symptoms . H . pylori was identified by culture from one site in 16 and two or more sites in 10 of the 16 patients . Five isolated colonies of six strains of H . pylori from gastric antrum were subcultured and used for further analysis . Antibiotic susceptibility to metronidazole and clarithromycin was determined by disk diffusion test . Protein profiles of isolates were compared by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) . DNA diversity of the isolates was determined by arbitrarily primed polymerase chain reaction (AP-PCR) fingerprinting . RESULTS: Of the 10 patients with multiple isolates, 70% (7/10) exhibited variation in susceptibility to metronidazole and 20% (2/10) to clarithromycin between different sites . In 83% of (5/6) single colonies, no variability was seen in metronidazole and clarithromycin susceptibility; they were either susceptible or resistant . Protein profiles of all isolates by SDS-PAGE were similar . Isolates from different patients produced clearly different AP-PCR fingerprints . In 50% of H . pylori strains isolated from different sites of the stomach, genetic diversity was demonstrated by different AP-PCR fingerprints . In 67% (4/6) strains, five single-colony fingerprints were similar . CONCLUSIONS: Genetic variability has been found in H . pylori strains . Individual patients are infected with a single predominant genotype at a single site but can be colonized by multiple strains, and they may show different antibiotic susceptibilities . Individual colonies of the H . pylori population from a single site may not always yield identical DNA fingerprints and antibiotic sensitivities.

J Surg Res, 2001 Jul, 99(1), 33 - 9
Ventral incisional hernia recurrence; Clark JL; During the period October 1993 to December 1996, 31 patients were operated on by the author for primary or recurrent ventral incisional hernia (VIH) . Three patients were excluded from analysis because their records were unavailable for review . The median age of the 28 remaining patients at their initial procedure was 57.5 years (range, 37-78 years) . The repair was performed with interrupted O-Ethibond sutures in all but 3 cases where Prolene suture was used secondary to noniatrogenic contamination or recurrent hernia . There were no unplanned enterotomies in the entire series and prophylactic intravenous antibiotics were used in all cases . The only significant complications were skin hyperemia after five repairs in 3 patients who were treated empirically with intravenous antibiotics, and 1 patient who had an antibiotic-associated rash . There were no 30-day mortalities . Prolene mesh was used exclusively in all repairs performed with mesh . Seven of these repairs (25%) were for recurrent VIH . Three of these seven patients had previous mesh repairs . Six of these seven patients who presented with recurrent VIH had a mesh repair and four developed a recurrence . Five of seven were active smokers, with one having severe obstructive lung disease . Four of seven related significant occupational lifting . Of the 21 patients having initial repair of VIH, mesh was used in 8 (38%) . After a median follow-up of 13 months, there were 2 recurrent hernias (25%) . The remaining 13 patients had primary closure of their hernias . After median follow-up of 25 months, there were 5 recurrences (38%) . A total of 34 VIH repairs were performed on these 28 patients, of which 13 were for recurrent hernias . Five of thirteen (38%) of the mesh repairs for recurrent VIH failed . The median body mass index (BMI) for the 13 patients having primary repair was 26.4, and that for all 21 cases having mesh repair was 28.8 . Patients with recurrent VIH frequently recur despite use of mesh, avoidance of contamination, and consistent technique . No difference in BMI was apparent in those who recurred . Continued smoking and occupational lifting may be important risk factors for recurrent VIH .

Biochim Biophys Acta, 2001 Jul 2, 1527(1-2), 1 - 3
Photodynamic action of actinomycin D: an EPR spin trapping study; Pan JX et al.; Actinomycin D is one of the most widely studied anticancer antibiotic that binds to both double-stranded and single-stranded DNA, and this binding greatly enhances the DNA photosensitization . By use of electron paramagnetic resonance spin trapping techniques, both superoxide radical anion and the radical anion of actinomycin D were identified as important intermediates in the photodynamic process . A mechanism of electron transfer from a DNA base to excited actinomycin D was proposed . These novel findings may shed new light on future application of this drug in photodynamic therapy or cleavage of DNA in unique and controllable ways.

Arch Gynecol Obstet, 2001 May, 265(2), 64 - 6
Laser therapy in chronic cervicitis; Dalgic H et al.; Chronic cervicitis is one of the common disorders encountered in daily practice . To overcome this problem first step should be antibiotic therapy in acute phase . If this fails, the infection becomes chronic and may spread to internal genital organs leading to pelvic inflammatory disease and eventually to infertility . Chronic form of infection may necessitate tissue destruction to prevent the development of dysplasia and neoplasm . Various methods such as electrocautery, loop diathermy, cryotherapy or laser are used to destroy the inflamed area . In this study we present 26 cases of chronic cervicitis managed with Nd-YAG laser with a success rate of 93% . We advice this method to block the development of cervical intraepithelial neoplasm.

J Am Osteopath Assoc, 2001 May, 101(5 Suppl), S8 - 13
Sinusitis in children: the importance of diagnosis and treatment; Shrum KM et al.; The complications from untreated sinusitis in a 10-month-old male infant, though at the more severe end of the spectrum, brings to light the importance of diagnosis and treatment even in the very young patient . Acute sinusitis should be diagnosed using established guidelines . Appropriate pharmacologic and osteopathic manipulative treatment should be initiated on diagnosis . Initial antibiotic therapy is a 14-day course of amoxicillin . If the sinusitis fails to resolve, a trial of a second-line antibiotic should be considered . The use of adjunctive medications such as antihistamines, decongestants, and nasal steroids remains controversial . If the patient fails maximal medical therapy, a computed tomography scan and referral to an otolaryngologist for possible surgical intervention should be considered.

Ann Pharmacother, 2001 Jun, 35(6), 675 - 81
Topical phenytoin treatment of stage II decubitus ulcers in the elderly; Rhodes RS et al.; OBJECTIVE: To compare the healing of stage II decubitus ulcers with topically applied phenytoin sodium with two other standard topical treatment procedures in a long-term care setting; and to assess the extent of systemic absorption after topical application in the phenytoin group . METHODS: Forty-seven nursing home patients with stage II decubitus ulcers were chosen for this study . The patients were matched for age, gender, and size and severity of wounds, and randomly assigned to each treatment group . Clinical assessment of decubitus ulcers was performed at the beginning of treatment and at each dressing change . Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing . Two phenytoin sodium plasma concentrations were to be obtained on all patients in the phenytoin group . RESULTS: Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications (p < or = 0.05) . The mean +/- SD time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively . Healthy granulation tissue in the phenytoin group appeared within two to seven days in all subjects . Patients in the standard treatment groups required six to 21 days to produce new granulation tissue . Serum phenytoin sodium concentrations were nondetectable . No patient withdrew from the study secondary to adverse treatment effects . CONCLUSIONS: Both the phenytoin and standard treatment groups showed progress over the study period . However, the phenytoin group demonstrated more rapid results in all aspects of ulcer healing.

Bioorg Med Chem Lett, 2001 Jun 18, 11(12), 1511 - 5
DNA alkylation by leinamycin can be triggered by cyanide and phosphines; Zang H et al.; Previous work has shown that alkylation of DNA by the antitumor agent leinamycin (1) is potentiated by reaction of the antibiotic with thiols . Here, it is shown that other soft nucleophiles such as cyanide and phosphines can also trigger DNA alkylation by leinamycin . Overall, the results suggest that reactions of cyanide and phosphines with leinamycin produce the oxathiolanone intermediate (2), which is known to undergo rearrangement to the DNA-alkylating episulfonium ion 4.

Indian J Pediatr, 2001 Apr, 68 Suppl 2, S26 - 32
Approach to recurrent respiratory infections; Bhave SY; Rational approach to diagnosis and management of recurrent respiratory infections is needed, or else the child is subjected to unnecessary investigations and multiple drugs . Repeated respiratory symptoms do not mean a respiratory infection . A diagnosis of viral infection does not justify prescription of an antibiotic . Recurrent viral infections are part of the growing up process of any child . Giving antibiotics at every episode to cover "so-called superadded bacterial infections" will lead to "recurrent antibiotics" and adverse effects on growth . Systematic approach should be used to find the underlying cause . An otoscopic examination of a child should form part of a pediatric examination in all cases of respiratory infections . Antibiotics should be judiciously chosen depending on age, socioeconomic status, severity of infection and the type of organism expected and always given in adequate doses and proper duration . Treatment should be specific and symptomatic . Adequate drainage of the sinuses is an important adjuvant therapy . Use of cough syrups with various combinations should be avoided . Efforts should be made to diagnose and treat manifestations of hyperactive airway or allergy, role of CEA (cough equivalent asthma) and WLRI (Wheeze associated lower respiratory infections) . Investigations are needed in recent lower respiratory infections and adverse effect on growth, school performance, abnormal physical findings . CBC, CRP, ESR, nasal smear, appropriate cultures, tests for TB, X-Rays, barium studies, milk scan, ultra sound, CT, MRI, bronchoscopy in selected cases.

J Nephrol, 2001 Mar-Apr, 14(2), 104 - 9
Congenital nephrotic syndrome: a clinico-pathologic study of thirty children; Hamed RM et al.; BACKGROUND: Congenital nephrotic syndrome is an uncommon disorder that may be caused by several diseases . These may be inherited, sporadic, acquired or part of a general malformation syndrome . METHODS: We reviewed the clinical characteristics, pathologic findings, and results of medical management in 30 infants who presented to Jordan University Hospital with congenital nephrotic syndrome in the years 1989 to 1999 . RESULTS: Most patients (80%) had parents who were consanguineous . Most patients (80%) were born premature, with an average gestational age of 36 weeks . Most infants (77%) presented the nephrotic syndrome in the first three months of life and 26 (87%) had significant growth retardation . Twenty-five verified episodes of serious bacterial infections occurred in 18 patients . Antibiotic therapy however was successful in all these episodes . Light microscopy of the renal biopsies was consistent with the Finnish type of congenital nephrosis in most patients (83%) . Chronic renal insufficiency developed in 17, and five of them needed chronic peritoneal dialysis . Most patients were given albumin transfusion and diuretic therapy especially during episodes of severe edema . Captopril alone or in combination with ibuprofen was given to eight patients, but without a response in any of them . All patients died before the age of 5 years . Most deaths occurred at an average age of 15 months (range 1-60) . CONCLUSION: The Finnish type of congenital nephrosis was the most common type in our patients, most of whom died within a few months of the onset of disease . In the developing countries, the management of patients with congenital nephrosis may have to be different from that in the developed countries in view of the high cost of medical management, poor outcome, high risk of serious complications, and high mortality rate.

Nucleic Acids Res, 2001 Jun 15, 29(12), E59 - 9
Yeast vectors for integration at the HO locus; Voth WP et al.; We have constructed new yeast vectors for targeted integration of desired sequences at the Saccharomyces cerevisiae HO locus . Insertion at HO has been shown to have no effect on yeast growth, and thus these integrations should be neutral . One vector contains the KanMX selectable marker, and integrants can be selected by resistance to G418 . The other vector contains the hisG-URA3-hisG cassette, and integrants can be selected by uracil prototrophy . Subsequent growth on 5-FOA permits identification of colonies where recombination between the hisG tandem repeats has led to loss of the URA3 marker and return to uracil auxotrophy . We also describe several new bacterial polylinker vectors derived from pUC21 (ampicillin resistance) and pUK21 (kanamycin resistance).

Clin Cancer Res, 2001 Jun, 7(6), 1490 - 6
Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia; Bross PF et al.; PURPOSE: Gemtuzumab ozogamicin (Mylotarg; Wyeth Laboratories, Philadelphia, PA) consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML) . In this study, we review the preclinical and clinical profiles of this immunoconjugate and the regulatory review that led to marketing approval by the United States Food and Drug Administration . EXPERIMENTAL DESIGN: From the literature and manufacturer's data, we review the activity, tolerability, and pharmacokinetics of gemtuzumab ozogamicin in preclinical and Phase I studies and its activity, efficacy, and side effects in three Phase 2 trials of 142 patients with relapsed AML . RESULTS: In Phase I studies, the major toxicity was myelosuppression, especially neutropenia and thrombocytopenia, resulting from the expression of CD33 on myeloid progenitor cells . The Phase 2 dose was 9 mg/m(2) infused i.v . over 4 h, repeated on day 14 . A minority of patients experienced acute infusion-related symptoms, usually transient and occasionally requiring hospitalization . The complete response (CR) rate with full recovery of hematopoiesis was 16% . A subset of patients {CRs with incomplete platelet recovery (CRps)} was identified with blast clearance and neutrophil recovery but incomplete platelet recovery . The duration of responses of CRps appeared to be similar to those of the CRs, although the numbers were small . The question of the equivalence of these response groups was a central issue in the review of this new drug application (NDA) . After considerable discussion, the Oncology Drugs Advisory Committee recommended allowing inclusion of CRps resulting in an overall response rate in the Phase 2 studies of 30% . In the subgroup of patients over 60 years of age, the overall response rate was 26% . Response duration was difficult to establish because of the high prevalence of postremission therapies . Tolerability and ease of administration may be improved compared with conventional chemotherapy, except for hepatotoxicity, with 31% of patients exhibiting abnormal liver enzymes . One patient died of liver failure in the Phase 2 trials . CONCLUSIONS: Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by the United States Food and Drug Administration under the Accelerated Approval regulations . Gemtuzumab ozogamicin is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy . The approved dose was 9 mg/m(2) i.v . over 4 h and repeated in 14 days . Completion of the ongoing studies of gemtuzumab ozogamicin in relapsed AML and initiation of randomized clinical trials comparing the effects of gemtuzumab ozogamicin in combination with conventional induction chemotherapy to conventional chemotherapy alone on survival are mandated to confirm clinical benefit under the accelerated approval Subpart H regulations . Postmarketing reports of fatal anaphylaxis, adult respiratory distress syndrome (ARDS), and hepatotoxicity, especially venoocclusive disease (VOD) in patients treated with gemtuzumab ozogamicin, with and without associated hematopoietic stem cell transplantation (HSCT), have required labeling revisions and the initiation of a registration surveillance program . Tumor lysis and ARDS have been reported in patients with leukocytes above 30,000/ml treated with gemtuzumab ozogamicin; therefore, the reduction of leukocyte counts to below 30,000/ml is recommended prior to treatment . Patients should be carefully monitored for acute hypersensitivity, hypoxia, and delayed hepatotoxicity following treatment with gemtuzumab ozogamicin.

Chem Biol, 2001 Jun, 8(6), 557 - 67
Two sequence elements of glycosyltransferases involved in urdamycin biosynthesis are responsible for substrate specificity and enzymatic activity; Hoffmeister D et al.; BACKGROUND: Two deoxysugar glycosyltransferases (GTs), UrdGT1b and UrdGT1c, involved in urdamycin biosynthesis share 91% identical amino acids . However, the two GTs show different specificities for both nucleotide sugar and acceptor substrate . Generally, it is proposed that GTs are two-domain proteins with a nucleotide binding domain and an acceptor substrate site with the catalytic center in an interface cleft between these domains . Our work aimed at finding out the region responsible for determination of substrate specificities of these two urdamycin GTs . RESULTS: A series of 10 chimeric GT genes were constructed consisting of differently sized and positioned portions of urdGT1b and urdGT1c . Gene expression experiments in host strains Streptomyces fradiae Ax and XTC show that nine of 10 chimeric GTs are still functional, with either UrdGT1b- or UrdGT1c-like activity . A 31 amino acid region (aa 52-82) located close to the N-terminus of these enzymes, which differs in 18 residues, was identified to control both sugar donor and acceptor substrate specificity . Only one chimeric gene product of the 10 was not functional . Targeted stepwise alterations of glycine 226 (G226R, G226S, G226SR) were made to reintroduce residues conserved among streptomycete GTs . Alterations G226S and G226R restored a weak activity, whereas G226SR showed an activity comparable with other functional chimeras . CONCLUSIONS: A nucleotide sugar binding motif is present in the C-terminal moiety of UrdGT1b and UrdGT1c from S . fradiae . We could demonstrate that it is an N-terminal section that determines specificity for the nucleotide sugar and also the acceptor substrate . This finding directs the way towards engineering this class of streptomycete enzymes for antibiotic derivatization applications . Amino acids 226 and 227, located outside the putative substrate binding site, might be part of a larger protein structure, perhaps a solvent channel to the catalytic center . Therefore, they could play a role in substrate accessibility to it.

Cancer Res, 2001 Jun 15, 61(12), 4731 - 9
Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells; Dorrie J et al.; Resveratrol, a plant antibiotic, has been found to have anticancer activity and was recently reported to induce apoptosis in the myeloid leukemia line HL60 by the CD95-CD95 ligand pathway . However, many acute lymphoblastic leukemias (ALLs), particularly of B-lineage, are resistant to CD95-mediated apoptosis . Using leukemia lines derived from patients with pro-B t(4;11), pre-B, and T-cell ALL, we show in this report that resveratrol induces extensive apoptotic cell death not only in CD95-sensitive leukemia lines, but also in B-lineage leukemic cells that are resistant to CD95-signaling . Multiple dose treatments of the leukemic cells with 50 microM resveratrol resulted in >/=80% cell death with no statistically significant cytotoxicity against normal peripheral blood mononuclear cells under identical conditions . Resveratrol treatment did not increase CD95 expression or trigger sensitivity to CD95-mediated apoptosis in the ALL lines . Inhibition of CD95-signaling with a CD95-specific antagonistic antibody indicated that CD95-CD95 ligand interactions were not involved in initiating resveratrol-induced apoptosis . However, in each ALL line, resveratrol induced progressive loss of mitochondrial membrane potential as measured by the dual emission pattern of the mitochondria-selective dye JC-1 . The broad spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone failed to block the depolarization of mitochondrial membranes induced by resveratrol, further indicating that resveratrol action was independent of upstream caspase-8 activation via receptor ligation . However, increases in caspase-9 activity ranged from 4- to 9-fold in the eight cell lines after treatment with resveratrol . Taken together, these results point to a general mechanism of apoptosis induction by resveratrol in ALL cells that involves a mitochondria/caspase-9-specific pathway for the activation of the caspase cascade and is independent of CD95-signaling.

Mediators Inflamm, 2001 Apr, 10(2), 61 - 7
Improvement of nutrient absorption may enhance systemic oxidative stress in cystic fibrosis patients; Shmarina GV et al.; BACKGROUND: The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the pulmonary disease severity and progress . Malnutrition may be an important complicating factor in active and chronic lung disease . AIMS: The focus of this study was to investigate several inflammatory markers in pancreatic-insufficient CF patients with different enzyme treatment regimens . METHODS: CF patients with pancreatic insufficiency were examined at a time of symptomatic exacerbation of their lung disease . Group A (n = 11) regularly received microspheric enzymes . Group B (n = 8) were treated with enzymes during the hospitalization period only and demonstrated the presence of malnutrition . Inflammatory markers in the sputa (neutrophil elastase activity, interleukin-8 and tumour necrosis factor-alpha levels) and in the peripheral blood (plasma malondialdehyde (MDA), lymphocyte response to PHA, and the cell sensitivity to steroid suppression) have been investigated . RESULTS: During acute lung exacerbation, group B demonstrated reduced levels of lymphocyte proliferation . This parameter was normalized after combined antibiotic and pancreatic enzyme therapy . Simultaneously, plasma MDA in group B markedly increased following treatment . For this group, a significant positive linear association between values of plasma MDA and lymphocyte proliferation has been observed . For group A, neither the same correlation nor changes in MDA levels and lymphocyte proliferation have been found . CONCLUSIONS: Our data indicate that acute lung exacerbation in malnourished CF patients may be associated with alteration in T-lymphocyte activity . Adequate therapy normalizes lymphocyte function but results in systemic oxidative stress.

Radiologe, 2001 May, 41(5), 439 - 41
{Acute hematogenous osteomyelitis--exclusion with Turbo-STIR sequence?}; Wunsch R et al.; The timely diagnosis and early initiation of antibiotic therapy determine the clinical course of an acute hematogenous osteomyelitis . Consequently, a fast and efficient MRI examination protocol is crucial . We retrospectively evaluated various MR sequences used in the examination of 8 children having osteomyelitis . The examinations were conducted using a 0.5 T MR machine . All patients had a high signal intensity of the lesion in the IR sequence with fat suppression (turbo-STIR) . An acute osteomyelitis can be excluded in the absence of signal intensity increase in the turbo-STIR sequence without the necessity of having to perform additional sequences.

Eur J Cardiothorac Surg, 2001 Jun, 19(6), 811 - 6
Deep sternal wound infection: the role of early debridement surgery; De Feo M et al.; OBJECTIVE: This retrospective chart review study aimed to evaluate whether a more aggressive staged approach can reduce morbidity and mortality following post-cardiotomy deep sternal wound infection . METHODS: Between 1979 and 2000, 14620 patients underwent open heart surgery: mediastinitis developed in 124 patients (0.85%) . Patients were divided in two groups: in 62 patients (Group A) (1979-1994) an initial attempt of conservative antibiotic therapy was the rule followed by surgical approach in case of failure; in 62 patients (Group B) (1995-2000) the treatment was staged in three phases: (1) wound debridement, removal of wires and sutures, closed irrigation for 10 days; (2) in case of failure open dressing with sugar and hyperbaric therapy (11 patients, 17%); (3) delayed healing and negative wound cultures mandated plastic reconstruction (three patients, 4%) . Categorical values were compared using the Chi-square test, continuous data were compared by unpaired t-test . RESULTS: Incidence of mediastinitis was higher in Group B (62 out of 5535; 1.3%) than in Group A (62 out of 9085; 0.7%) (P=0.007) . Mean interval between diagnosis and treatment was shorter in Group B (18+/-6 days) than in group A (38+/-7 days) (P=0.001) . Hospital mortality was higher in Group A (19/62; 31%) than in Group B (1 out of 62; 1.6%) (P<0.001) . Hospital stay was shorter in Group B (30.5+/-3 days) than in group A (44+/-9 days) (P=0.001) . In Group B complete healing was observed in all the 61 survivors: 47 cases (76%) after Stage 1; 11 (18%) after Stage 2; three (4.8%) after Stage 3 . CONCLUSIONS: Although partially biased by the fact that the two compared groups draw back to different decades, this study showed that an aggressive therapeutic protocol can significantly reduce morbidity and mortality of deep sternal wound infection.

Diagn Microbiol Infect Dis, 2001 Apr, 39(4), 261 - 4
A case of splenic abscess due to Chlamydia pneumoniae; Bessho H et al.; In this report, a case of chlamydial disease with splenic abscess associated with Chlamydia pneumoniae antigen and antibody was described . On spleen biopsy of the patient, an antigen specific to C.pneumoniae was detected by immunofluorescence staining with a monoclonal antibody . Serologic studies revealed a high antibody titer to C.pneumoniae in sera collected from the patient and her husband . Treatment with the antibiotic minocycline improved her condition.

Fungal Genet Biol, 2001 Jun, 33(1), 37 - 48
Characterization of pisatin-inducible cytochrome p450s in fungal pathogens of pea that detoxify the pea phytoalexin pisatin; George HL et al.; Many fungi that are pathogenic on pea have the ability to demethylate and thus detoxify the pea phytoalexin pisatin . This detoxification reaction has been studied most thoroughly in Nectria haematococca MP VI where it functions as a virulence trait . The enzyme catalyzing this reaction {pisatin demethylase (pda)} is a cytochrome P450 . In the current study, the induction of whole-cell pda activity and the biochemical properties of pda in microsomal preparations from the pea pathogens Ascochyta pisi, Mycosphaerella pinodes, and Phoma pinodella are compared to the pda produced by N . haematococca . Based on cofactor requirements and their inhibition by carbon monoxide, cytochrome P450 inhibitors, and antibodies to NADPH:cytochrome P450 reductase, we conclude that the pdas from the other pea pathogens also are cytochrome P450s . All of the enzymes show a rather selective induction by pisatin, have a low K(m) toward pisatin, and have a fairly high degree of specificity toward pisatin as a substrate, suggesting that each pathogen may have a specific cytochrome P450 for detoxifying this plant antibiotic . Since the pdas in these fungi differ in their pattern of sensitivity to P450 inhibitors and display other minor biochemical differences, we suggest that these fungi may have independently evolved a specialized cytochrome P450 as a virulence trait for a common host .

Ann Otol Rhinol Laryngol, 2001 Jun, 110(6), 565 - 73
Cochlear microphonic potentials: a new recording technique; Carricondo F et al.; A new instrumentation and a particular method for detecting and recording cochlear microphonic potentials (CMPs) are described here . The CMPs were recorded in rats by means of pure tones (4,000, 2,000, 1,000, 500, and 250 Hz) and intraepidermic electrodes; the electrocochleography technique was avoided . An experimental design that included the use of a glutamatergic agonist (kainic acid {KA}) and an aminoglycoside antibiotic (kanamycin {KANA}) was carried out to demonstrate the origin of the recorded potential . Morphological studies showed that KA selectively eliminated the afferent type I dendrites of the spiral ganglion, while the administration of KANA resulted in the absence of outer hair cells . When CMPs were recorded after KA administration, no alterations were detected . In contrast, KANA administration resulted in the absence of any selective electrophysiological activity corresponding to CMPs . All these results were compared with the recording of the compound action potential of the eighth nerve obtained by electrocochleography . These findings and the great specificity of the reproduction of the sound stimulus confirm that the CMPs can be recorded by the new equipment.

Biophys Chem, 2001 May 18, 90(3), 219 - 32
Changes in 13C NMR chemical shifts of DNA as a tool for monitoring drug interactions; LaPlante SR et al.; The antibiotic drug, netropsin, was complexed with the DNA oligonucleotide duplex {d(GGTATACC)}2 to explore the effects of ligand binding on the 13C NMR chemical shifts of the DNA base and sugar carbons . The binding mode of netrospin to TA-rich tracts of DNA has been well documented and served as an attractive model system . For the base carbons, four large changes in resonance chemical shifts were observed upon complex formation: -0.64 ppm for carbon 4 of either Ado4 or Ado6, 1.36 ppm for carbon 2 of Thd5, 1.33 ppm for carbon 5 of Thd5 and 0.94 for carbon 6 of Thd5 . AdoC4 is covalently bonded to a heteroatom that is hydrogen bonded to netropsin; this relatively large deshielding is consistent with the known hydrogen bond formed at AdoN3 . The three large shielding increases are consistent with hydrogen bonds to water in the minor groove being disrupted upon netropsin binding . For the DNA sugar resonances, large changes in chemical shifts were observed upon netropsin complexation . The 2', 3' and 5' 13C resonances of Thd3 and Thd5 were shielded whereas those of Ado4 and Ado6 were deshielded; the 13C resonances of 1' and 4' could not be assigned . These changes are consistent with alteration of the dynamic pseudorotational states occupied by the DNA sugars . A significant alteration in the pseudorotational states of Ado4 or Ado6 must occur as suggested by the large change in chemical shift of -1.65 ppm of the C3' carbon . In conclusion, 13C NMR may serve as a practical tool for analyzing structural changes in DNA-ligand complexes.

Int J Food Microbiol, 2001 May 21, 66(1-2), 103 - 10
The management of VTEC O157 infection; Todd WT et al.; VTEC O157 infections, although showing a relentless rise in incidence over the last decade, only account for less than 10% of total food poisoning notifications in the UK . Despite this, the propensity for this infection to cause the serious and life-threatening clinical complications of haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP), in a significant proportion (2-15%) of sufferers, highlights the need to focus on it both epidemiologically and clinically . The mortality rate of these complications (3-17% and up to 30% in outbreaks) adds urgency to this consideration . The pathogenesis and epidemiology of the illness caused by VTEC O157 is now well described, allowing the potential for appropriate intervention in outbreak and individual clinical management . The presence or absence of symptoms, e.g . bloody diarrhoea, fever, vomiting, in VTEC O157 infections compared with other causes of gastroenteritis may allow some selection of cases for more intensive management . Age (< 15, > 65 years), clinical hypochlorhydria . and a short incubation period have been associated with complication (HUS/TTP) development . Antibiotic therapy in the pre-infection period may predispose to complication development and there is evidence that it may increase complications if used in the management of acute illness . Laboratory markers such as early neutrophil leukocytosis have been shown both to correlate with VTEC O157 infection and to predict complications in central Scotland and Japan . The serum albumin and the C-reactive protein may act as additional markers for HUS development . Laboratory markers may be differentiated into those predicting HUS/TTP and those useful in monitoring its development . A scheme for clinical management of affected cases is presented to allow the attending clinician to select cases that may benefit from further intervention to prevent or treat complications.

Neurochirurgie, 2001 May, 47(2-3 Pt 1), 123 - 7
{Dermal sinus and dermoid cyst revealed by abscess formation in posterior fossa . Report of 2 pediatric cases and review of the litterature}; Hayek G et al.; Cranial dermal sinus, usually associated with dermoid cyst, is the persistance of an abnormal embryonal communication between the skin and the central nervous system . It may be the source of intracranial infection, most often a meningitis and rarely an abscess formation . Two cases of little girls (18 months and 2 years) having dermal sinus with dermoid cyst revealed by cerebellar abscess formations are reported . In the first case there were multiple cerebellar abscesses with hydrocephalus leading to a raised intracranial pressure . In the second case there was an abscess formation adjacent to the dermoid cyst . CT scan showed cysts and abscesses but MRI, achieved in the second case, was useful in demonstrating the sinus tract as well as the associated cyst and abscess . The two patients underwent a posterior fossa surgery with antibiotic therapy . In the first case abscess drainage and ventricular external drainage were necessary before sinus and cyst excision . Two months after surgery the two patients were neurologically intact and developping well . Surgery with total excision of dermal sinus and dermoid cyst, even sometimes difficult, must be preferred to the simple abscess drainage and antibiotic therapy.

Head Neck, 2001 Jul, 23(7), 594 - 8
Cutaneous botryomycosis of the cervicofacial region; Yencha MW et al.; BACKGROUND: Botryomycosis is a rare, chronic, bacterial infection of insidious onset involving the integument or viscera that often mimics actinomycosis or a deep fungal infection . The pathogenesis is thought to be a symbiotic relationship between the host and the infecting organism . METHODS: Case report of a patient with a chronic infection involving the cervicofacial region diagnosed as cutaneous botryomycosis arising from a chronic osteomyelitis of the mandible . The diagnosis was based on the chronicity of the infection along with the identification of botryomycotic (bacteria-containing) granules on histopathologic examination . Special stains excluded fungi and mycobacterium . Cultures identified the offending bacteria, and antibiotic therapy was initiated on the basis of the sensitivities, resulting in resolution of this chronic infectious process . A review of the English language literature revealed that this is the first case of cutaneous botryomycosis arising from a chronic osteomyelitis of the mandible . RESULTS: Medical therapy proved curative at 14 months follow-up . Surgery was performed for diagnostic purposes only . CONCLUSIONS: Botryomycosis is exceedingly rare in the head and neck, and consideration of this entity in the differential diagnosis is critical to the diagnosis . The mainstay of therapy is medical with surgery reserved for biopsy and/or excision of persistent disease . Published 2001 John Wiley & Sons, Inc.

Chest, 2001 Jun, 119(6), 1966 - 8
Utility of Wang needle aspiration in the diagnosis of actinomycosis; Bakhtawar I et al.; An 85-year-old man had a 4-year history of recurrent pneumonia with a persistent pleural effusion . He underwent repeated bronchoscopy that revealed a right bronchus intermedius mass, but bronchial washes and biopsies remained nondiagnostic . A repeat bronchoscopy was performed, and a Wang needle aspiration of the mass was obtained that showed sulfur granules, diagnosing actinomycosis . The patient was started on appropriate antibiotic therapy . Actinomycosis must be considered in a patient with recurrent pneumonia and an endobronchial mass . Wang needle aspiration via bronchoscopy may be an important diagnostic tool.

Chest, 2001 Jun, 119(6), 1742 - 8
Safety and efficacy of two courses of OM-85 BV in the prevention of respiratory tract infections in children during 12 months; Gutierrez-Tarango MD et al.; BACKGROUND: Acute respiratory tract infections (ARTIs) are among the main causes of morbidity and mortality in children . The bacterial extract OM-85 BV (bronchovaxom) has shown protective effect for ARTIs on children . We report a double-blind, placebo-controlled, parallel, prospective clinical trial to assess the safety and efficacy of two courses of OM-85 BV in the prevention of ARTIs in susceptible children during 12 months . METHODS: Fifty-four susceptible children from 1 to 12 years of age living in the metropolitan area of Chihuahua City were selected . They were randomized to receive either OM-85 BV or placebo (one capsule a day for 10 days a month for 3 consecutive months) at the beginning of the trial and 6 months later with the same schedule . Patients were followed up for 12 months, including the administration period . The trial began in July 1997 and ended in April 1999 . RESULTS: The number (mean +/- SD) of ARTIs was 5.04 +/- 1.99 (median, 5.0) in the OM-85 BV group vs 8.0 +/- 2.55 (median, 8.0) in the placebo group, with a mean difference of - 2.96 (95% confidence interval {CI}, - 4.22 to - 1.7) . The number of antibiotic courses was 2.46 +/- 2.08 (median, 1.5) in the treatment group vs 4.46 +/- 2.08 (median, 4.0) in the control group, a difference of - 2.0 (95% CI, - 3.14 to - 0.86) . The total duration of ARTIs was 35.23 +/- 17.64 days (median, 30.5 days) in the OM-85 BV group vs 60.75 +/- 25.44 days (median, 55.0 days) in the placebo group, ie, a difference of - 25.52 days (95% CI, - 37.56 to - 13.47 days), p < 0.001 by Student's t test and Mann-Whitney U test for all the items . Four patients in the OM-85 BV group had five adverse events . Only one episode of skin rash was related to the medication intake . Six patients in the control group had six adverse events . CONCLUSIONS: OM-85 BV had a preventive effect on ARTI in the susceptible children for 12 months with an important reduction on the antibiotic requirements and the number of days of suffering ARTIs.

Hematology, 2000, 5(2), 167 - 172
Therapy: Hyperbaric Oxygen as the Only Effective Treatment in Mutilating and Resistant Systemic Vasculitis; Jacobs P et al.; A forty year old man was seen in 1984 with a four year history of a painful vasculitis that responded transiently to plasma exchange . Diagnosis was revised to atypical pyoderma gangrenosum with further temporary benefit from lamprene and continuing maximally tolerated corticosteroids . The course fluctuated over the next ten years with gradual and increasing soft-tissue damage coupled with superimposed skin infections . A variety of organisms were isolated from the ulcerated areas, with each episode successfully managed on the basis of local debridement and appropriate antibiotic administration . In 1995, with extending skin devascularization, infectious bacterial episodes became more frequent and deep non-healing ulcers led to constant pain with virtual incapacity . In response to protocol hyperbaric oxygen therapy there was immediate reversal of the cutaneous damage, granulation tissue formed and new skin grew to cover the previous extensive deficits . As the lesions in his hands and feet improved so did his quality of life, with the patient again becoming ambulant and returning to work . Vascular access had become a major problem, and venography showed extensive occlusion with collateral circulation . A standard Hickman catheter was placed through the femoral vein into the inferior vena cava and functioned well over the next five years . At the end of 1996 the patient was admitted with an acute chest pain that was complicated by a major pulmonary embolus, from which he could not be resuscitated . This anecdotal experience demonstrates the important but underutilised benefits of hyperbaric oxygen in managing refractory, painful and penetrating skin ulcers . The cost of obtaining wound healing with reduction in pain by this form of treatment was approximately one-fifth of expenditure on previously ineffective management.

Hematology, 1999, 4(4), 305 - 311
Malignancy: Granulocyte Colony Stimulating Factor Increases the Efficacy of Conventional Amphotericin in the Treatment of Presumed Deep-Seated Fungal Infection in Neutropenic Patients following Intensive Chemotherapy or Bone Marrow Transplantation for Haematological Malignancies; Hazel DL et al.; A prospective, comparative study of empiric amphotericin B with, or without, granulocyte colony stimulating factor was carried out to assess whether the addition of granulocyte colony stimulating factor to empiric amphotericin B improves the clinical response in neutropenic patients with suspected or proven fungal infection . Fifty nine neutropenic adults with haematological malignancy and antibiotic-refractory fever or clinical evidence of deep-seated fungal infection were studied . Patients received intravenous colloidal amphotericin B (1 milligram per kilogram body weight) with or without subcutaneous granulocyte colony stimulating factor (three to five micrograms per kilogram body weight) . Thirty patients received amphotericin alone and 29 amphotericin plus granulocyte colony stimulating factor . Nearly twice as many patients responded to amphotericin B with concomitant administration of granulocyte colony stimulating factor (62%) as responded to amphotericin alone (33%; difference in proportions 0.29, 95%CI 0.03-0.54) . Clinical response in patients receiving granulocyte colony stimulating factor coincided with neutrophil recovery in most cases . Addition of granulocyte colony stimulating factor to empiric amphotericin B significantly reduced the number of patients requiring salvage therapy with lipid-associated or liposomal formulations of amphotericin B addition of granulocyte colony stimulating factor to empiric intravenous amphotericin B improves the response rate and thereby reduces the number of patients requiring salvage therapy with liposomal or lipid-associated preparations of amphotericin B.

Best Pract Res Clin Gastroenterol, 2001 Jun, 15(3), 433 - 45
Role of acid suppressants in prophylaxis of NSAID damage; Chan FK et al.; Gastric acid contributes to the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced ulceration via several mechanisms, including conversion of superficial to deeper injury, impairment of haemostasis, and interference with ulcer healing . The suppression of acid secretion has been shown to reduce the severity of NSAID-induced mucosal damage in experimental models and clinical studies . Current evidence indicates that proton pump inhibitors (PPIs) are the preferred treatment for the healing of gastric ulcers when NSAIDs cannot be discontinued . PPIs are superior to standard-dose H(2)-receptor antagonists and equivalent to low-dose misoprostol in preventing NSAID-induced gastric ulcers . Whether there is any significant advantage of PPIs over higher doses of H(2)-receptor antagonists or misoprostol is unknown . The efficacy of PPIs is enhanced in the presence of H . Pylori infection . Omeprazole has been shown to be effective for the secondary prevention of ulcer bleeding in H . pylori -infected NSAID users . The efficacy of PPIs for the prevention of ulcer complications in H . pylori-negative NSAID users remains uncertain.

Acta Vet Hung, 2000, 48(3), 361 - 8
Studies on the toxic interaction between monensin and tiamulin in rats: effects on P450 activities; Szucs G et al.; Studies were carried out to investigate the effects of monensin and tiamulin, and the simultaneous administration of both compounds on microsomal enzymes in rats . In Phase I of the experiments the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively), while in Phase II the two compounds were administered simultaneously (monesin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively) . When monensin was administered by itself, it exerted no significant effect on microsomal liver enzymes . In a few cases, slight inhibition of certain enzyme activities was seen . Tiamulin provoked a dose-dependent hepatic enzyme induction . The combined administration of monensin and tiamulin at low doses (10 and 40 mg/kg, respectively) resulted in marked elevation of P450-related enzyme activities . The enzyme induction was more pronounced in females than in males . The results suggest that the simultaneous administration of tiamulin may influence the biotransformation of monensin, possibly increasing the amount of reactive metabolite(s) of the ionophore antibiotic.

Rev Med Interne, 2001 May, 22(5), 433 - 9
{Evaluation of a hospitalization unit opened during the winter influenza epidemic of 1999-2000}; Roger PM et al.; PURPOSE: Last winter, a great many patients with influenza-like infection were admitted to our hospital, leading us to open a specific unit for 6 weeks . We report the evaluation of medical care given to these patients . METHODS: Useful data for evaluating care to patients presenting respiratory infections were determined beforehand by the retrospective analysis of patients' charts . RESULTS: Fifty-seven out of 185 admitted patients (31%) had infectious respiratory symptoms . The mean age was 81 years . Six cases of influenza virus infection, 43 cases of viral bronchitis, six cases of bacterial pneumonia, one superinfected asthma and one septic shock were diagnosed . All patients presented with cardiac and/or chronic pulmonary diseases . Influenza vaccination had been performed in 28 patients (49%) . Before hospitalisation, 30 patients (52%) had received antibiotics, and 17 (30%) a steroid therapy . In contrast, only 12 patients (21%) have received anti-infective agents during the hospitalisation . Twenty-five patients were able to go back home and a nursing home was required for 27 patients (47%); five patients died . Tools for improving this specific department in a public hospital are discussed . CONCLUSION: Vaccinations in the elderly appear to be poorly utilized; meanwhile, antibiotic treatments, as well as steroid therapy, are overused . Managing epidemic infections requires attention from the public hospital system.

Sex Transm Infect, 2001 Jun, 77(3), 214 - 7
The control of syphilis, a contemporary problem: a historical perspective; Green T et al.; The control of syphilis in the United Kingdom and United States has been managed in different ways in each country over the course of the last century . Older more established measures including contact tracing, serological surveillance, and health education strategies together with effective antibiotic therapy have had some success . However, changing social structures on both sides of the Atlantic Ocean have brought newer mathematical and epidemiological methods to the fore . This review looks at the past management of syphilis control in the United Kingdom and United States, and speculates on future prospects for disease management in these countries.

Mol Microbiol, 2001 May, 40(4), 857 - 68
In vitro and in vivo nucleotide exchange directed by chimeric RNA/DNA oligonucleotides in Saccharomyces cerevisae; Rice MC et al.; Targeted gene repair directed by chimeric RNA/DNA oligonucleotides has proven successful in eukaryotic cells including animal and plant models . In many cases, however, there has been a disparity in the levels of gene correction or frequency . While the delivery of these chimera into the nucleus and the long-term stability or purity of these molecules may contribute to this variability, understanding the molecular regulation of conversion is the key to improving or stabilizing frequency . To this end, we have identified genes that control targeted repair, using the genetically tractable organism, Saccharomyces cerevisae and a bank of yeast mutants . Results from experiments in cell-free extracts focused our attention on RAD52, RAD1 and RAD59 as central regulatory factors . RAD1 and RAD59 appear to be required for high levels of conversion whereas RAD52 appears to act, surprisingly, in a suppressive fashion . Results from the in vitro experiments were translated into targeting experiments in vivo . Here, mutations in a fusion construct, containing a marker gene, were converted to wild type, evidenced by the expression of green fluorescence in converted cells . Because the repaired fusion gene contains a corrected neomycin sequence, cells were subsequently placed under G418 selection and conversion confirmed at the genetic level . Taken together, these results establish, for the first time, genes that participate in the regulation of targeted gene repair and provide a novel system for evaluating true frequencies of correction . Importantly, this system enables visualization of corrected (green) and uncorrected (clear) cells enabling measurements of conversion in real time.

Biochemistry, 2001 Jun 19, 40(24), 7092 - 8
Cyclization of backbone-substituted peptides catalyzed by the thioesterase domain from the tyrocidine nonribosomal peptide synthetase; Trauger JW et al.; The excised C-terminal thioesterase (TE) domain from the multidomain tyrocidine nonribosomal peptide synthetase (NRPS) was recently shown to catalyze head-to-tail cyclization of a decapeptide thioester to form the cyclic decapeptide antibiotic tyrocidine A {Trauger, J . W., Kohli, R . M., Mootz, H . D., Marahiel, M . A., and Walsh, C . T . (2000) Nature 407, 215-218} . The peptide thioester substrate was a mimic of the TE domain's natural, synthetase-bound substrate . We report here the synthesis of modified peptide thioester substrates in which parts of the peptide backbone are altered either by the replacement of three amino acid blocks with a flexible spacer or by replacement of individual amide bonds with ester bonds . Rates of TE domain catalyzed cyclization were determined for these substrates and compared with that of the wild-type substrate, revealing that some parts of the peptide backbone are important for cyclization, while other parts can be modified without significantly affecting the cyclization rate . We also report the synthesis of a modified substrate in which the N-terminal amino group of the wild-type substrate, which is the nucleophile in the cyclization reaction, is replaced with a hydroxyl group and show that this compound is cyclized by the TE domain to form a macrolactone at a rate comparable to that of the wild-type substrate . These results demonstrate that the TE domain from the tyrocidine NRPS can catalyze cyclization of depsipeptides and other backbone-substituted peptides and suggest that during the cyclization reaction the peptide substrate is preorganized for cyclization in the enzyme active site in part by intramolecular backbone hydrogen bonds analogous to those in the product tyrocidine A.

Biochem Biophys Res Commun, 2001 Mar 30, 282(2), 511 - 4
Effect of membrane fluidity on tyrosine kinase activity of reconstituted epidermal growth factor receptor; Ge G et al.; Epidermal growth factor receptor (EGFR) was functionally reconstituted into liposome membrane . Triton X-100 was removed by Bio-beads SM-2 . More than 80% of the reconstituted EGFR possessed right-side-out orientation with the EGF binding side facing the medium . The tyrosine kinase assay of the EGFR was carried out in the presence of the antibiotic alamethicin . The reconstituted EGFR tyrosine kinase was well activated by EGF . The influence of lipid composition on tyrosine kinase activity was investigated . Introduction of cholesterol into the dioleoylphophatidylcholine (DOPC) liposome membrane resulted in the decrease of tyrosine kinase activity . The tyrosine kinase activity of EGFR in distearylphosphatidylcholine liposome was much lower than that of EGFR-DOPC proteoliposome . Results indicated the importance of membrane fluidity on the apparent tyrosine kinase activity of reconstituted EGFR .

Biochim Biophys Acta, 1974 Apr 27, 349(1), 39 - 46
Differential effects of analogs of cycloheximide on protein and RNA synthesis in Achlya; Timberlake WE et al.; Analogs of the glutarimide antibiotic cycloheximide were tested for their effect on growth and incorporation of proline and uridine into acid-insoluble material in Achlya bisexualis . Each of the compounds tested had reduced antibiotic activity as compared to cycloheximide . The effects of the antibiotics on protein and RNA synthesis were varied . While cycloheximide inhibited both protein and RNA synthesis immediately, two of the analogs inhibited proline incorporation without effect on uridine incorporation, while three, each representing a modification of the hydroxyl of cycloheximide, stimulated uridine incorporation and either had no effect on or inhibited protein synthesis . These results indicate that the control of RNA synthesis by protein synthesis in Achlya can be released by glutarimide antibiotics.

J Toxicol Sci, 2001 May, 26 Suppl 1, 1 - 4
{Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (1)--Single oral and intravenous dose toxicity studies in rats}; Yahara I et al.; A single oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) and a single intravenous dose toxicity study of its sodium salt (S-1090-Na) were conducted in rats . One dose level of 2000 mg potency/kg was set in both studies . Single oral dose toxicity study of S-1090 No deaths occurred . Diarrhea occurred on the dosing day and slightly soft feces lasted until 6 days after administration . These changes were considered to result from changes of intestinal flora induced by the antibiotic activity of S-1090 . Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were also observed until the next day after administration . Body weights increased favorably, and no S-1090-related pathological changes were observed . The oral lethal dose of S-1090 was estimated to be more than 2000 mg potency/kg . Single intravenous dose toxicity study of S-1090-Na No deaths occurred . The rats showed characteristic clinical signs such as hypoactivity, abnormal gait and hypopnea immediately after dosing, and some rats showed prone position or paleness of eyeballs and ear auricles in due course . These signs disappeared by 4 hr after administration . Slightly soft feces and reddish-brown feces were observed much the same as in the orally-treated rats . Body weights increased favorably . In the pathological examinations, slight cecal enlargement and increased basophilia, dilatation and calcification of the renal tubules in the kidney were observed . The intravenous lethal dose of S-1090-Na was estimated to be more than 2000 mg potency/kg.

Anal Biochem, 2001 Jun 15, 293(2), 258 - 63
A high-throughput screen for identifying transmembrane pore-forming peptides; Rausch JM et al.; We have developed a visual microwell plate assay for rapid, high-throughput screening for membrane-disrupting molecules such as de novo designed pore formers, antibiotic peptides, bacterial toxins, and lipases . The detectability is based on the strong fluorescence emission of the lanthanide metal terbium(III) (Tb(3+)) when it interacts with the aromatic chelator dipicolinic acid (DPA) . While Tb(3+) is not strongly fluorescent alone, the binary complex emits bright green fluorescence when irradiated with uv light . For the microwell plate assay, we prepared unilamellar phospholipid vesicles that had either Tb(3+) or DPA entrapped and the opposite molecule in the external solution . Disruption of the membranes allows the Tb(3+)/DPA complex to form, giving rise to a visibly fluorescent solution . In plates with 20-microl wells, the lower limit of visual detectability of the Tb(3+)/DPA complex in solution was about 2.5 microM . The lower limit of detectability using vesicles with entrapped Tb(3+) or DPA was about 50 microM phospholipid . We show that the membrane-disrupting effect of as little as 0.25 microM or 5 pmol of the pore-forming, antibiotic peptide alamethicin can be detected visually with this system . This sensitive, high-throughput assay is readily automatable and makes possible the visual screening of combinatorial peptide libraries for members that permeabilize lipid bilayer membranes .

Anal Biochem, 2001 Jun 15, 293(2), 246 - 50
Preferred binding sites for {N-MeCYs(3), N-MeCys(7)}TANDEM determined using a universal footprinting substrate; Lavesa M et al.; We have prepared a novel footprinting substrate which contains all 136 tetranucleotide sequences and have used this to determine the preferred binding sites for the synthetic quinoxaline antibiotic {N-MeCys(3),N-MeCys(7)}TANDEM . We find that, although the ligand binds to all TpA steps, it binds best to the tetranucleotide sequence ATAT and shows only weak interaction with TTAA and GTAC . The best binding sites contain the sequences ATAX and XTAT .

Eur J Clin Microbiol Infect Dis, 2001 Apr, 20(4), 260 - 2
Risk factors for catheter-associated bacteriuria in a medical intensive care unit; Tissot E et al.; In a prospective study including 137 consecutive catheterised patients in a medical intensive care unit, the following variables were analysed as possible risk factors for catheter-associated bacteriuria, defined as a quantitative culture with > or = 10(5) organisms/ml: age, sex, simplified acute and physiologic score at admission, duration of catheterisation, diabetes mellitus, immunosuppression, neurologic disorders and prior systemic antibiotic exposure during hospitalisation . The frequency of catheter-associated bacteriuria was 30.7% . By multivariate analysis, female sex (odds ratio {OR}, 5.1; 95% confidence interval {CI}, 1.9-13.5; P=0.001) and a duration of catheterisation >11 days (OR, 19.4; 95% CI, 5.5-68.7; P=0.0001) were risk factors for catheter-associated bacteriuria, and prior antibiotic exposure was a protective factor (OR, 0.06; 95% CI, 0.019-0.21; P=0.0001).

Radiol Med (Torino), 2001 Apr, 101(4), 251 - 4
{Acute pyelonephritis . Role of diagnostic imaging}; Parenti GC et al.; PURPOSE: To asses the role of imaging in acute pyelonephritis by retrospectively evaluating a number of cases observed with special care to US and CT signs that may be useful for an early and correct diagnostic assessment . MATERIAL AND METHODS: From 1994 to the first quarter of 2000 we observed 95 patients clinically suspected of having acute pyelonephritis (81 females and 14 males, age range 2-80 years; 75% were under 40 years old) . Sonography was performed as an emergency in 78 patients . CT scan with contrast media was performed in acute phase in 78 patients acquiring the images in the pre-contrastographic phase, 60 s after the administration of contrast media (portal phase), after 5 to 10 min (excretory phase), and after 3 to 6 hours (very late phase) . In 47 patients, diagnosed as having acute pyelonephritis, a follow-up CT scan was performed at 30 days, 45 days, 3 months and 6 months from the acute episode . RESULTS: In 78 of the patients clinically suspected of having acute pyelonephritis, the CT examination allowed to assess the presence or lack of the inflammatory focus . In 17 cases US discovered causes other than acute pyelonephritis on admission; in 25 out of 61 patients it allowed assessment of a pyelonephritic focus that was confirmed with CT . The CT examination with contrast media proved to be a reliable and fondaments method in the diagnosis of pyelonephritic focus especially as it revealed the lack of concentration of contrast media in the flogistic foci, in the very late fase . This method furthermore allows to discover alterations in peri and pararenal regions and to rule out abscesses and renal infarcts . US had a sensitivity of 50% and a specificity of 70% in the diagnosis of acute pyelonephritis, but those may be improved by power Doppler . DISCUSSION AND CONCLUSIONS: In suspected acute pyelonephritis US offers useful indications for a quick and correct diagnostic assessment, but CT examination with contrast media proved to be more reliable than US . In our experience US and above all CT examination rapidly identified patients affected by acute pyelonephritis, thereby allowing us institute a timely antibiotic therapy and obtain a brilliant therapeutic response.

Vet Ophthalmol, 1999, 2(3), 155 - 161
Comparison of Optisol-GS and neomycin-polymyxin B-gramicidin ophthalmic solution for corneal storage in the dog; Andrew SE et al.; The objective of the research was to compare the efficacy of Optisol-GS (OGS, Bausch & Lomb Surgical, Irvine, CA, USA) with triple antibiotic ophthalmic solution (neomycin-polymyxin B-gramicidin, NPG; Bausch & Lomb, Tampa, FL, USA) in preserving the viability of corneal endothelial cells . The study subjects were thirty young to middle-aged dogs with no gross corneal pathology that had been euthanized by pentobarbital overdose for reasons unrelated to this project . Corneal tissues were harvested, analyzed, and randomly assigned to treatment groups: one of two media (OGS or NPG), and one of five storage times (1, 7, 14, 21, or 35 days) . Six corneas were stored in each medium for each time period . Corneal endothelial cell viability was evaluated pre- and poststorage by vital staining (trypan blue and alizarin red S), and endothelial cell morphology was evaluated with scanning electron microscopy . Storage in NPG caused significant loss (100%) of endothelial cells after all storage times . OGS storage maintained a high level of endothelial cell viability up to 21 days (98.9% +/- 1.3% viability) . A significant decrease in percentage viability was also found for OGS-stored corneas between 21 and 35 days, when endothelial cell viability decreased to 61.4% +/- 45.9% . The conclusions are that NPG storage at -20 degrees C is a very poor choice of media for corneal tissue banking if graft clarity is the goal . Storage in Optisol-GS at 4 degrees C for up to 21 days resulted in significantly higher percentages of viable endothelial cells . Optisol-GS storage should facilitate corneal preservation for canine keratoplasty patients.

Drug Ther Bull, 2001 May, 39(5), 33 - 7
Acute complications of sickle cell disease in children; Effects of bronchoalveolar lavage volume on arterial oxygenation in mechanically ventilated patients with pneumonia; Medizinische Klinik und Poliklinik, Abt . Pneumologie, Allergologie und Schlafmedizin, Bergmannsheil, Klinikum der Ruhr-Universitat, Bochum, GermanyOBJECTIVE: To assess the effect of bronchoalveolar lavage (BAL) volume on arterial oxygenation in critically ill patients with pneumonia . DESIGN: Randomized clinical comparison . SETTING: Six-bed respiratory intensive care unit of a 850-bed tertiary care university hospital . PATIENTS: Thirty-seven intubated and mechanically ventilated patients with clinical suspicion of pneumonia . INTERVENTIONS: Bronchoscopically guided protected specimen brush (PSB) followed by either a "high volume" BAL (n = 16, protected catheter, mean volume: 131 +/- 14 ml) or a "low volume" BAL (n = 21, protected double-plugged catheter, 40 ml volume for all patients) . MEASUREMENTS: Arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2) and mean arterial pressure (MAP) before and up to 24 h after the intervention . Bacterial growth in quantitative cultures . Analysis of variance for repeated measurements with inter-subject factors . RESULTS: All patients showed a lower PaO2/FIO2 ratio and higher MAP after the diagnostic procedure, without differences between the study arms (p = 0.608 and p = 0.967, respectively) . Patients with significant bacterial growth (p = 0.014) and patients without preemptive antibiotic (p = 0.042) therapy showed a more profound and longer decrease in arterial oxygenation after the diagnostic procedure . CONCLUSIONS: A decrease in the PaO2/FIO2 ratio was observed in all patients after a combined diagnostic procedure, independent of the BAL volume used . A significant bacterial burden recovered from the alveoli and no preemptive antibiotic therapy were associated with a larger and longer-lasting decrease in arterial oxygenation.

Arch Pediatr, 2001 May, 8(5), 499 - 503
{Dermoid cysts revealed by meningitis with medullary compression}; Raqbi F et al.; The spinal dermal sinus tracts in the lumbosacral region are not usually recognized, especially when they are not associated with other cutaneous lesions . In these sites, the sinus tracts communicate with the dura in 90% of cases, leading to an important risk of meningitis . CASE REPORTS: Two infants (9 and 12 months old) were hospitalized for meningitis . The hospitalization was preceded two weeks earlier by stubborn constipation, which revealed a neural compression . The physical and MRI examination showed a lumbosacral sinus in contact with a dermoid or an epidermoid tumor . These cysts were infected with anaerobic organisms . Despite surgery and antibiotic therapy, one child remained paraplegic . CONCLUSION: Dermal sinuses above the intergluteal crease should be surgically excised at the time of diagnosis in all patients, regardless of the patient's age or neurologic findings.

Med Klin (Munich), 2001 May 15, 96(5), 287 - 91
{Reactive hemophagocytosis syndrome as a rare cause of fatal pancytopenia}; Kulemann JE et al.; CASE REPORT: We present the case of a feverish 36-year-old female patient with unspecific pain and weight loss . After initial diagnosis of an unclear infection with Candida esophagitis, unspecific duodenitis, proctitis and liver damage there was a further clinical deterioration during antibiotic and symptomatic therapy . A newly developed pancytopenia could be identified as caused by reactive hemophagocytosis using bone marrow analysis . The patient died despite maximal supportive and specific therapy . Cause of death was a retroperitoneal hematoma and an invasive aspergillosis, the latter not identified premortem . CONCLUSION: The reactive infect-associated hemophagocytosis is a rare differential diagnosis in feverish pancytopenia . The prognosis is poor . In absence of a proven causal therapy supportive therapy and maximal diagnostics for detection of curable underlying diseases are essential . Antimycotic therapy should be considered generally.

Surg Endosc, 2001 Apr, 15(4), 398 - 401 Epub 2000 Dec 12.
Treatment of acute cholecystitis . A comparison of open vs laparoscopic cholecystectomy; Glavic Z et al.; BACKGROUND: In this study, the clinical results and cost-effectiveness of open vs laparoscopic cholecystectomy in the treatment of acute cholecystitis were compared . METHODS: Over a 5-year period (1994-98), 894 cholecystectomies were performed, 545 (60.96%) of them laparoscopically and 349 (39.04%) by the open method . The study included 209 patients with a clinical diagnosis of acute cholecystitis; 115 (55.02%) of them were operated on by the open method and 94 (44.98%) by the laparoscopic method . RESULTS: A comparison analysis revealed that the mean postoperative treatment period was 8.40 days after open and 4.38 days after laparoscopic cholecystectomy . In the group operated on by the open method, 106 patients received an antibiotic, a mean of 5.09 ampules and 3.2 tablets or suppositories of an analgesic, and 2.91 dressings per patient; whereas in the group submitted to the laparoscopic method, the comparable figures were 43, 3.13, 2.1, and 1.47, respectively . In 31 (26.96%) employed patients operated on by the open method, the mean absenteeism from work was 42 days; whereas in 31 (32.98%) of those operated on by the laparoscopic method, it was 17 days . The mean operating times for the procedures were 89 and 115 min for the open and laparoscopic methods, respectively . Two patients submitted to open cholecystectomy died within 30 days postoperatively . Wound infection was recorded in 10 (8.7%), prolonged biliary secretion in two, and cicatricial hernia in five (4.35%) patients . In the group submitted to laparoscopic cholecystectomy, there were no deaths; nine (9.57%) conversions were required; four patients had to be reoperated on, two of them for bile lobe hemorrhage and two for massive biliary secretion from the open cystic duct; herniation at the site of supraumbilical incision developed in three patients, and infection developed at the same site in two (2.13%) patients . The hospital cost was significantly higher in laparoscopic patients ($1181 vs $873) USD), as was the total cost of treatment for acute cholecystitis ($1430 vs $1316) . However, the cost for sick leave and rehabilitation was significantly lower in laparoscopically treated patients ($486 vs $1199) . CONCLUSIONS: Our comparison analysis of the results and cost-effectiveness of the surgical treatment of acute cholecystitis clearly pointed to the advantages of laparoscopic over open cholecystectomy-i.e., better clinical outcome and a more rapid resumption of daily activities . Hospital and total costs of treatment were on average higher in laparoscopic patients, except for the employed ones, where the lower sick leave cost translated into a significant reduction in total costs.

Crit Care Med, 2001 Jun, 29(6), 1159 - 63
Indocyanine green elimination rate detects hepatocellular dysfunction early in septic shock and correlates with survival; Kimura S et al.; OBJECTIVE: To determine whether indocyanine green clearance is an early indicator of hepatocellular injury in septic shock and to assess its predictive value . DESIGN: Observational study with prospective data collection . SETTING: Traumatology and critical care unit in a city hospital, staffed by traumatology and intensive care clinicians . PATIENTS: Twelve patients in septic shock who survived at least 2 months (group S) and nine patients who died within 2 wks (group N) . INTERVENTIONS: Routine resuscitation from septic shock (surgery, fluid loading, and administration of catecholamines and antibiotic drugs) . MEASUREMENTS AND MAIN RESULTS: Pulmonary artery occlusion pressure, cardiac index, oxygen delivery index, oxygen consumption index, and the indocyanine green elimination rate constant (KICG; or the slope of the loge {indocyanine green concentration} vs . time curve) 3-9 mins after injection were measured within 12 hrs of the onset of hypotension, then at 24 hrs, and every 24 hrs thereafter . Alanine aminotransferase and total bilirubin were measured on day 0 and day 1 . Volume of fluid administered and duration of shock were the same in survivors and nonsurvivors . The oxygen consumption index was higher in survivors at 12 hrs, but no intergroup difference in pulmonary artery occlusion pressure, cardiac index, or oxygen delivery index was significant at any time point . KICG in nonsurvivors was lower than in survivors both initially and after 24 hrs, and it was subnormal in all patients except one survivor (p <.05) . The KICG increased between 24 and 120 hrs in 11 survivors but progressively decreased and remained below 0.05 in seven nonsurvivors . The remaining two nonsurvivors died within 24 hrs of the initial measurement of KICG, which was >0.05 . Alanine aminotransferase and total bilirubin were less sensitive measures of hepatic dysfunction in the first 24 hrs than the KICG . CONCLUSIONS: The KICG can identify reversible liver injury in septic shock, suggesting good prognosis . Either failure to increase the KICG within 120 hrs or an extremely low KICG is a poor prognostic sign.

J Bacteriol, 2001 Jul, 183(13), 3890 - 902
Genome-wide transcriptional profiling of the Escherichia coli responses to superoxide stress and sodium salicylate; Pomposiello PJ et al.; Escherichia coli responds to oxidative stress by activating sets of coregulated genes that help the cell to maintain homeostasis . Identified previously by genetic and biochemical approaches, the soxRS system mediates the induction of 18 of these redox-inducible genes (including the soxS gene itself) . An overlapping set of genes is activated by an assortment of structurally unrelated molecules with antibiotic activities; many genes in this response are controlled by the marRAB system . The activation of either the soxRS or the marRAB system results in enhanced resistance to both superoxide-generating agents and multiple antibiotics . In order to probe the extent of these regulatory networks, we have measured whole-genome transcriptional profiles of the E . coli response to the superoxide-generating agent paraquat (PQ), an inducer of the soxRS system, and to the weak acid salt sodium salicylate (NaSal), an inducer of the marRA system . A total of 112 genes was modulated in response to PQ, while 134 genes were modulated in response to NaSal . We have also obtained transcriptional profiles of the SoxS and MarA regulons in the absence of global stress, in order to establish the regulatory hierarchies within the global responses . Several previously unrelated genes were shown to be under SoxS or MarA control . The genetic responses to both environmental insults revealed several common themes, including the activation of genes coding for functions that replenish reducing potential; regulate iron transport and storage; and participate in sugar and amino acid transport, detoxification, protein modification, osmotic protection, and peptidoglycan synthesis . A large number of PQ- and NaSal-responsive genes have no known function, suggesting that many adaptive metabolic changes that ensue after stress remain uncharacterized.

Microbios, 2001, 105(411), 103 - 9
Effect of the raw extracts of Arthrinium strains (Hyphomycetes, Dematiaceae) on the growth of some deleterious fungi in poultry feed; Aissaoui H et al.; In previous work the authors have shown that some species of the Arthrinium genus are characterized by being able to produce secondary metabolites with antibiotic activity . The aim of this study was to evaluate the effect of raw extracts of the growth of three different Arthrinium strains against Aspergillus flavus, Aspergillus nidulans, Fusarium moniliforme and Penicillium purpurogenum when they were present in poultry feed . The results showed that the extracts reduced the growth of Aspergillus flavus and Fusarium moniliforme but could not inhibit the development of Aspergillus nidulans . Only the raw extract of A . aureum inhibited the growth of Penicillium purpurogenum.

Intern Med, 2001 May, 40(5), 403 - 4
Isolated tricuspid valve endocarditis due to Candida parapsilosis associated with long-term central venous catheter implantation; Saito Y et al.; A 72-year-old man was treated for fungal tricuspid valve endocarditis (TVE) with significant tricuspid valvular regurgitation and severe congestive heart failure caused by Candida parapsilosis . The patient had received hyperalimentation and antibiotic therapy for three months through a central venous catheter after the surgical treatment of ileus . The patient was treated medically with amphotericin B and fluconazole because of high surgical risk due to severe pulmonary emphysema, and he responded well . Although TVE caused by C . parapsilosis is rare, we should consider this possibility in patients receiving long-term hyperalimentation and antibiotic therapy using a central venous catheter.

J Int Med Res, 2001 Mar-Apr, 29(2), 61 - 73
Moxifloxacin in acute exacerbations of chronic bronchitis: clinical evaluation and assessment by patients; Lorenz J et al.; The clinical success of a 5-day course of oral moxifloxacin (administered once daily at a dose of 400 mg) was evaluated in 328 patients with acute exacerbations of chronic bronchitis (Anthonisen type 1) in a non-comparative study conducted by chest physicians in private practice . Results were assessed on the basis of clinical parameters and, for the first time in a trial involving oral moxifloxacin, by the surrogate marker of patient satisfaction . Improvement in (and severity of) cough, dyspnoea, chest pain and sputum were scored daily by patients . Cough, chest pain and purulent sputum production improved rapidly within the first 5 days of treatment . At least 90% of patients were satisfied with the antibiotic . The clinical success rate (cure and improvement) for all patients involved (intent-to-treat analysis) was 90.5% . The most commonly experienced adverse events were gastrointestinal related, with diarrhoea the most frequent of these (2.7% of all patients).

Biol Trace Elem Res, 2001 Apr, 80(1), 33 - 42
Serum magnesium, copper, and zinc alterations following spinal fusion; Tatari H et al.; Changes in serum magnesium, copper and zinc values were evaluated in spinal fusion patients at four monitorings . For magnesium and copper individually, a significant difference was found between the mean values at each monitoring (p < 0.05), whereas the changes of zinc values between four monitorings were insignificant . There was no statistical difference between the changes of each trace element values and gender, age, operative time, intraoperative blood loss, blood replacement, number of the vertebral levels fused, and antibiotic type used . As a result, magnesium can be suggested to be more important than the other two elements in the postoperative period . Alterations of serum magnesium, copper, and zinc values do not have any correlation with the fusion of the spinal column, either with the width of the fused area or operative time and blood loss . This study cannot confirm the exact reason for this entity and the etiology remains speculative . There is no need for magnesium, copper, or zinc supplementation during the surgical period for the patients . It will be worthy to evaluate the patients who were sent to the intensive care unit after spinal surgery and compare their results with the other intensive care patients.

Hum Exp Toxicol, 2001 Apr, 20(4), 199 - 203
Effect of dimethyl sulfoxide on gentamicin-induced nephrotoxicity in rats; Ali BH et al.; Nephrotoxicity of gentamicin (GM) has been suggested to be mediated by the generation of reduced oxygen metabolites . The present study investigated the possible protective role of the free radical scavenger dimethyl sulfoxide (DMSO) on some indices of GM nephrotoxicity in rats . The antibiotic was injected intramuscularly (i.m.) at a dose of 100 mg/kg for six consecutive days, either with or without treatment with DMSO (12.5%, 25% or 50% in saline) at an intraperitoneal (i.p.) dose of 2 ml/kg 4 days before GM, and concomitantly with GM treatment thereafter . DMSO (25% in saline) was also given as above to rats treated with GM at i.m . doses of 25, 50 or 100 mg/kg for six consecutive days . GM caused dose-dependent significant increases in the concentrations of urea and creatinine in plasma, and in thiobarbituric acid reactive substances (TBARS) level in the kidney cortex and also caused significant decreases in the concentrations of reduced glutathione (GSH) and superoxide dismutase (SOD) activity . In GM-treated rats, DMSO dose-dependently lowered the elevated plasma urea and creatinine concentrations, and the rise in cortical TBARS . It also restored the levels of GSH and SOD activity to near normal . DMSO (25%) was effective in completely preventing the development of signs of nephrotoxicity of G (50 mg/kg) . Treatment of the rats with DMSO alone, at any of the above doses, did not alter significantly any of the renal or hepatic function tests studied, and did not appear to adversely affect the kidney or liver histology . However, the efficacy and safety of DMSO require further studies . It is suggested that DMSO has potential protective effect against GM nephrotoxicity in rats.

Jpn J Antibiot, 2001 Mar, 54(3), 103 - 11
{Evaluation of polymerase chain reaction method for monitoring of fungal infection in compromised hosts}; Ohta K et al.; Diagnosis of fungal infections in compromised hosts has been difficult because of insufficient sensitivity and specificity of conventional methods such as culturing and serum testing . Therefore, antifungal agents are usually started in febrile patients who are resistant to antibiotics even if these monitoring tests were negative . In this study, therefore, in order to increase the reliability of these monitoring, polymerase chain reaction (PCR) methods for detection of blood fungus were also performed in compromised hosts including 14 patients with hematological malignancies and one with solid tumor who were undergoing chemotherapies . From these patients, total of 56 peripheral blood samples was collected periodically, irrespective of the presence of infectious signs . At each time point of venopuncture, status of the patient was allocated to one of the followings: A, receiving an intravenous antifungal therapy because of sustaining fever which had not responded to prior antibiotic therapies and also positive for culturing and/or serum beta-D-glucan tests; B, receiving an additional intravenous antifungal therapy but negative for culturing and serum-tests; C, febrile but not yet receiving any intravenous fungal therapy; D, afebrile status . During the study, 10 blood samples from 3 patients were allocated in group A, and one sample of them was positive while remaining 9 were all negative for PCR . Six samples from 4 patients were in group B, and one was PCR positive while remaining 5 were negative . Fifteen samples from 7 patients were in group C, and 3 were positive and 12 were negative for PCR . Twenty-five samples were in group D, and 5 were positive and 20 were negative for PCR . Thus, the results from fungal PCR in these patients were in some case showed discrepancies from those expected from the clinical course and/or conventional monitoring tests . Further evaluation of fungal PCR may gain insight into the more precise diagnosis of fungal infection in these patients.

Cas Lek Cesk, 2001 Apr 26, 140(8), 230 - 3
{Care of patients with the diabetic foot syndrome based on an international consensus}; Jirkovska A; In the last year an International Consensus on the Diabetic Foot has been developed by a group of independent experts from all over the world . The definition of the diabetic foot is based on WHO criteria as infection, ulceration and/or destruction of deep tissues associated with neurological abnormalities and various degrees of peripheral vascular disease in the lower limb . It is one of the most serious complications of diabetes: approximately 50% of all non-traumatic amputations are performed on patients with diabetes, it is a frequent cause of hospitalisation and disability of diabetic patients . Comprehensive prevention and therapy of diabetic foot provided by a podiatric team may reduce the number of amputations by 50% and it may decrease substantially the cost of long-lasting therapy . In all countries foot-care management should be organised at the general practitioner and podiatric nurse level and specialised foot centres with a diabetologist, a podiatric nurse, a radiologist, general, orthopaedic and vascular surgeons, an orthopaedic technician and a physiotherapist should be formed . The podiatric team has the following responsibilities--to identify patients at high risk and monitor them and to treat patients with ulcers . Treatment of diabetic foot must include non-weight bearing, long-lasting antibiotic therapy, improving circulation and topical treatment-debridement.

Cancer Chemother Pharmacol, 2001 May, 47(5), 429 - 36
The vitamin D3 analog, ILX-23-7553, enhances the response to adriamycin and irradiation in MCF-7 breast tumor cells; Chaudhry M et al.; Ionizing radiation and the anthracycline antibiotic, Adriamycin, generally fail to promote a primary apoptotic response in experimental breast tumor cell lines . Similarly, the primary response of breast tumor cells to vitamin D3 (1,25(OH)2D3) and vitamin D3 analogs such as EB 1089 is growth inhibition . Previous studies have demonstrated that pretreatment of MCF-7 breast tumor cells with vitamin D3 or EB 1089 can increase sensitivity to both Adriamycin and irradiation . PURPOSE: The capacity of the vitamin D3 analog, ILX 23-7553, to enhance the antiproliferative and cytotoxic effects of Adriamycin or irradiation and to promote apoptosis in MCF-7 breast tumor cells was assessed in the present study . RESULTS: Pretreatment of MCF-7 cells with ILX 23-7553 followed by Adriamycin or irradiation decreased viable cell numbers by 97% and 93%, respectively . Cell numbers were reduced by 56%, 74% and 75% by ILX 23-7553, Adriamycin and irradiation alone . Pretreatment with ILX 23-7553 also shifted the dose response curve for clonogenic survival, increasing sensitivity to Adriamycin 2.5-fold and sensitivity to radiation fourfold . In addition, ILX 23-7553 pretreatment conferred sensitivity to Adriamycin- or irradiation-induced DNA fragmentation and resulted in morphological changes indicative of apoptotic cell death in MCF-7 cells . Statistical analysis demonstrated that ILX 23-7553 interacts additively and not synergistically with both Adriamycin and irradiation . CONCLUSIONS: ILX 23-7553 enhances the effects of Adriamycin and irradiation in MCF-7 breast tumor cells by decreasing viable cell numbers, reducing clonogenic survival and inducing apoptotic cell death . Current studies are focused on elucidating the mechanisms underlying the induction of apoptosis as well as understanding the nature of the interactions between ILX 23-7553 and Adriamycin or irradiation.

J Mol Recognit, 2001 May-Jun, 14(3), 145 - 50
Actinomycin D binding to unstructured, single-stranded DNA; Yoo H et al.; Actinomycin D is an anticancer antibiotic best know for inhibiting transcription by binding double-stranded DNA . Tight, sequence selective binding of actinomycin to single-stranded DNA is also known, however, and is implicated in biological activities including inhibition of (-) strand transfer by HIV reverse transcriptase . Oligonucleotide d(GTTAACCATAG) is one of the rare single-stranded DNAs that lack GC steps yet have high affinity for actinomycin . Oligonucleotide sequence and length requirements for drug binding were investigated by monitoring association of the fluorescent surrogate, 7-aminoactinomycin D, to d(GTTAACCATAG) and 31 related oligomers . The TAG-3' terminal sequence was essential for high-affinity binding, but was not sufficient . Five oligomers with TAG sequences on or near the 3'-end had high affinity {K(d) < or = 200 nM (oligomer)} . A sixth oligomer, d(GTAACCATATG), had moderately lower affinity (Kd = 370 nM), and other homologous oligomers had much lower affinity . The minimum length sequence for tight binding of 7-aminoactinomycin D was identified as only eight nucleotides, corresponding to d(AACCATAG) . This octanucleotide is unstructured in the absence of actinomycin, and has the highest drug affinity of all oligomers examined (Kd = 125 nM) . These studies show that high-affinity binding of 7-aminoactinomycin, and actinomycin D by extension, to single-stranded DNA does not require pre-existing secondary structure or any apparent propensity for secondary structure . It is proposed that actinomycin D binds to certain single-stranded DNA sequences by an induced-fit mechanism favored by participation of at least eight nucleotides, or the equivalent of four base pairs .

Am J Hematol, 2001 Jul, 67(3), 206 - 9
Early onset Pneumocystis carinii pneumonia after allogeneic peripheral blood stem cell transplantation; Saito T et al.; Pneumocystis carinii (P . carinii) is one of the major opportunistic pathogens responsible for hematopoietic stem cell transplantation (HSCT)-related pneumonias . Although trimethoprim-sulfamethoxazol (TMP/SMX) prophylaxis has been shown to prevent almost all P . carinii infections, 1%-2% of patients may still experience this complication . P . carinii pneumonia (PCP) is usually a late complication in patients receiving TMP/SMX prophylaxis, with most cases occurring later than 2 months post-transplant . We report a patient who developed early onset PCP after allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical sibling donor . On day 12, the patient complained of dyspnea and cough . A chest X ray showed infiltrates in right upper lobe with bilateral pleural effusion . By the findings of Grocott stain on bronchoalveolar lavage fluid obtained on day 14, he was diagnosed as having PCP . Intravenous TMP/SMX failed to improve the lesion . This is the earliest onset PCP in the literature after HSCT despite the prophylactic administration of TMP/SMX before transplant .

J Pediatr, 2001 Jun, 138(6), 845 - 50
Long-term comparative trial of positive expiratory pressure versus oscillating positive expiratory pressure (flutter) physiotherapy in the treatment of cystic fibrosis; McIlwaine PM et al.; OBJECTIVE: The objective was to evaluate the long-term effects of physiotherapy with an oscillating positive pressure device ("flutter") compared with physiotherapy with the use of a positive expiratory pressure (PEP) mask in patients with cystic fibrosis (CF).Study design: Forty children with CF were randomly assigned to performing physiotherapy with the PEP mask or the flutter device for 1 year . Clinical status, pulmonary function, and compliance were measured at regular intervals throughout the study . RESULTS: The flutter group demonstrated a greater mean annual rate of decline in forced vital capacity compared with the PEP group (-8.62 +/- 15.5 vs 0.06 +/- 7.9; P =.05) with a similar trend in forced expiratory volume in 1 second (-10.95 +/- 19.96 vs -1.24 +/- 9.9; P =.08) . There was a significant decline in Huang scores (P =.05), increased hospitalizations (18 vs 5; P =.03), and antibiotic use in the flutter group . CONCLUSION: Flutter was not as effective in maintaining pulmonary function in this group of patients with CF compared with PEP and was more costly because of the increased number of hospitalizations and antibiotic use.

Cardiol Young, 2001 May, 11(3), 355 - 6
The role of tissue plasminogen activator in the successful treatment of infected cardiac thrombus in children; Zalzstein E et al.; Infected cardiac thrombus is rare in children, with antibiotic or antifungal agents used as the first line of treatment . Persistence is an indication for surgical intervention . We describe two children who were treated successfully with a combination of antibiotic and antithrombotic agents . Use of antithrombotic agents promotes degeneration of fibrin, thus reducing the mass and facilitating the diffusion of the antibiotic and/or antifungal agents.

Rozhl Chir, 2001 Apr, 80(4), 181 - 3
{Bacterial flora in obstructed bile ducts}; Pospisil M et al.; The authors present the results of bile cultivation from obturated bile ducts . The bile was obtained during ERCP . The results agree in principle with data reported in the literature . The authors emphasize the regional variability of bacterial strains and their sensitivity . It is thus an ever urgent problem which deserves attention, in particular preventive administration of antibiotics . At the authors department as preventive antibiotic cefoperazone proved useful.

Antonie Van Leeuwenhoek, 2000 Dec, 78(3-4), 237 - 42
Alteration of substrate specificity of valine dehydrogenase from Streptomyces albus; Hyun CG et al.; The catabolism of branched chain amino acids, especially valine, appears to play an important role in furnishing building blocks for macrolide and polyether antibiotic biosyntheses . To determine the active site residues of ValDH, we previously cloned, partially characterized, and identified the active site (lysine) of Streptomyces albus ValDH . Here we report further characterization of S . albus ValDH . The molecular weight of S . albus ValDH was determined to be 38 kDa by SDS-PAGE and 67 kDa by gel filtration chromatography indicating that the enzyme is composed of two identical subunits . Optimal pHs were 10.5 and 8.0 for dehydrogenase activity with valine and for reductive amination activity with alpha-ketoisovaleric acid, respectively . Several chemical reagents, which modify amino-acid side chains, inhibited the enzyme activity . To examine the role played by the residue for enzyme specificity, we constructed mutant ValDH by substituting alanine for glycine at position 124 by site-directed mutagenesis . This residue was chosen because it has been considered to be important for substrate discrimination by phenylalanine dehydrogenase (PheDH) and leucine dehydrogenase (LeuDH) . The Ala-124-Gly mutant enzyme displayed lower activities toward aliphatic amino acids, but higher activities toward L-phenylalanine, L-tyrosine, and L-methionine compared to the wild type enzyme suggesting that Ala-124 is involved in substrate binding in S . albus ValDH.

Obstet Gynecol, 2001 Jun, 97(6), 1019 - 23
Impact of infectious diseases on women's health: 1776-2026; Gibbs RS; In this commentary, the author reviews the impact of infectious diseases on women's health, beginning with the late 18th century when clinically recognized infections took the heaviest toll on women . The review continues through the 19th and 20th centuries when public health measures and the advent of antibiotic agents led to apparent control of infection, and ends with a forecast for the next 25 years . Foreboding considerations for the future include spread of human immune deficiency virus infection and other sexually transmitted diseases and the development of new infections, antibiotic-resistant bacteria, and the recognition of infection as a cause of many obstetric-gynecologic and chronic disorders . Obstetricians and gynecologists can contribute to the solution of these problems individually and collectively.

Ann Thorac Surg, 2001 May, 71(5), 1572 - 8; discussion 1578-9
Intranasal mupirocin reduces sternal wound infection after open heart surgery in diabetics and nondiabetics; Cimochowski GE et al.; BACKGROUND: This study was designed to determine whether decreasing nasal bacterial colonization by applying Mupirocin (MPN) intranasally decreases sternal wound infections . METHODS: We prospectively followed 992 consecutive open heart surgery (OHS) patients who did not receive MPN prophylaxis (group I) from January 1, 1995 to October 31, 1996 . Group II consisted of 854 consecutive patients followed prospectively from December 1, 1997 to March 31, 1999 treated with intranasal MPN given on the evening before, the morning of OHS, and twice daily for 5 days postoperatively . RESULTS: There was a significant difference in the rate of overall sternal wound infections between the untreated (group I) and the treated group (group II): 2.7% (27 of 992) versus 0.9% (8 of 854) (p = 0.005) . The difference was also significant in the diabetic subgroup: 5.1% (14 of 277) (group I) versus 1.9% (5 of 266) (group II) (p = 0.04) and the nondiabetic group: 1.8% (13 of 715) (group I) versus 0.5% (3 of 588) (group II) (p = 0.03) . The cost of MPN treatment was $12.47 per patient compared with $81,018 +/- $41,567 for a deep wound infection with no antibiotic-related complications recorded . CONCLUSIONS: Prophylactic intranasal MPN is safe, inexpensive, and very effective in reducing the overall sternal wound infections by 66.6%.

Neurosurgery, 2001 Jun, 48(6), 1393 - 9; discussion 1399-401
Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction; Sanchez Mejia RO et al.; OBJECTIVE: Caspase-1 plays an important functional role mediating neuronal cell death and dysfunction after experimental traumatic brain injury (TBI) in mice . Minocycline, a derivative of the antibiotic tetracycline, inhibits caspase-1 expression . This study investigates whether minocycline can ameliorate TBI-mediated injury in mice . METHODS: Brains from mice subjected to traumatic brain injury underwent immunohistochemical analyses for caspase-1, caspase-3, and a neuronal specific marker (NeuN) . Minocycline- and saline-treated mice subjected to traumatic brain injury were compared with respect to neurological function, lesion volume, and interleukin-1beta production . RESULTS: Immunohistochemical analysis revealed that activated caspase-1 and caspase-3 are present in neurons 24 hours after TBI . Intraperitoneal administration of minocycline 12 hours before or 30 minutes after TBI in mice resulted in improved neurological function when compared with mice given saline control, as assessed by Rotarod performance 1 to 4 days after TBI . The lesion volume, assessed 4 days after trauma, was significantly decreased in mice treated with minocycline before or after trauma when compared with saline-treated mice . Caspase-1 activity, quantified by measuring mature interleukin-1beta production by enzyme-linked immunosorbent assay, was considerably increased in mice that underwent TBI, and this increase was significantly diminished in minocycline-treated mice . CONCLUSION: We show for the first time that caspase-1 and caspase-3 activities localize specifically within neurons after experimental brain trauma . Further, these results indicate that minocycline is an effective pharmacological agent for reducing tissue injury and neurological deficits that result from experimental TBI, likely through a caspase-1-dependent mechanism . These results provide an experimental rationale for the evaluation of minocycline in human trauma patients.

Laryngorhinootologie, 2001 Apr, 80(4), 173 - 6
{Vestibular toxicity of gentamycin in newborn infants}; Aust G et al.; BACKGROUND: Gentamicin known as ototoxic drug is routinely used for treatment of vital infections in neonatologic departments . The aim of the present study is to clarify whether gentamicin has a vestibulotoxic effect when used in therapeutic levels in the newborn phase . METHOD: Children were taken on the knees of the mother or relative sitting on an electronically driven rotating chair . The rotatory stimulation consisted of an undamped sinusoidal stimulus pattern which was performed in total darkness . Horizontal and vertical eye movements were recorded electronystagmographically . PATIENTS: The patient group consisted of 30 children aged between 3.1 and 32.9 months . These children had been treated with gentamicin during the newborn period . A group of 30 healthy children of similar age without gentamicin treatment was the control group . RESULTS: The statistical means of the nystagmus reactions during sinusoidal rotation were similar in both groups . No increase of spontaneous eye movements was seen in the patients or in the control group . CONCLUSIONS: Gentamicin is an important antibiotic for treatment of life-threatening infectious diseases, which acts less ototoxically in controlled therapeutic doses in newborns than in later childhood or in adults.

Minerva Anestesiol, 2001 May, 67(5), 413 - 7
{Life threatening asthma associated to severe pneumonia and acute myopathy}; Girardis M et al.; A young male was transferred to our intensive care unit (ICU) from the intensive care unit of a local hospital where he was admitted for life-threatening asthma ten days before . As severe hypoxemia, we immediately started inhaled nitric oxide (iNO) that improved significantly pulmonary gas exchange . The first day after admission in our ICU, a chest computed tomography showed a three-lobar pneumonia and, therefore, a broad-spectrum antibiotic therapy was decided . iNO therapy was withdrawn 96 hours after the beginning because of a stable improvement of pulmonary gas exchange and a relative loss of efficacy . Five days after arrival in our ICU, sedative and neuromuscular blocking drugs initiated 15 days before were stopped and, after the awakening, the patient presented tetra-paresis . Muscle biopsy and electromyography indicated an acute myopathy that was probably caused by the association between large doses of steroids and neuromuscular blocking agents . In spite of an intensive physiotherapy program, the patient was extubated only 15 days after admission and he underwent non-invasive mechanical ventilation for further 7 days . The patient was discharged from our ICU 10 days after extubation with a good restore of muscle functioning which was complete two months later.

Aliment Pharmacol Ther, 2001 Jun, 15(6), 851 - 5
Fish oil (Eicosapen) is less effective than metronidazole, in combination with pantoprazole and clarithromycin, for Helicobacter pylori eradication; Meier R et al.; BACKGROUND: In vitro omega-3-fatty acids (Eicosapen) are bacteriostatic to Helicobacter pylori and have a variety of immuno-modulating effects . AIM: To investigate the efficacy and tolerability of eicosapen (E) as an antibiotic-sparing component of a triple H . pylori eradication regimen in non-ulcer dyspepsia patients in a randomized, double-blind trial . METHODS: Non-ulcer dyspepsia patients (n=199), with a normal upper endoscopy and a positive (13)C-urea breath test (UBT) were randomly assigned to either pantoprazole, clarithromycin and metronidazole (PCM) or pantoprazole, clarithromycin and eicosapen (PCE) for 7 days . Four weeks after treatment, H . pylori eradication was determined by UBT . Symptoms were followed up to 16 months . RESULTS: In the intention-to-treat population, PCM eradicated infection in 78% but PCE was successful in only 34% (P < 0.001) . Symptomatic improvement occurred in both groups, and was not related to H . pylori eradication . CONCLUSION: Eicosapen is unlikely to be useful in H . pylori eradication regimens.

J Heart Valve Dis, 2001 May, 10(3), 334 - 44; discussion 335
The homograft aortic valve: a 29-year, 99.3% follow up of 1,022 valve replacements; O'Brien MF et al.; BACKGROUND AND AIM OF THE STUDY: The study aim was to elucidate the advantages and limitations of the homograft aortic valve for aortic valve replacement over a 29-year period . METHODS: Between December 1969 and December 1998, 1,022 patients (males 65%; median age 49 years; range: 1-80 years) received either a subcoronary (n = 635), an intraluminal cylinder (n = 35), or a full root replacement (n = 352) . There was a unique result of a 99.3% complete follow up at the end of this 29-year experience . Between 1969 and 1975, homografts were antibiotic-sterilized and 4 degrees C stored (124 grafts); thereafter, all homografts were cryopreserved under a rigid protocol with only minor variations over the subsequent 23 years . Concomitant surgery (25%) was primarily coronary artery bypass grafting (CABG; n = 110) and mitral valve surgery (n = 55) . The most common risk factor was acute (active) endocarditis (n = 92; 9%), and patients were in NYHA class II (n = 515), III (n = 256), IV (n = 112) or V (n = 7) . RESULTS: The 30-day/hospital mortality was 3% overall, falling to 1.13 +/- 1.0% for the 352 homograft root replacements . Actuarial late survival at 25 years of the total cohort was 19 +/- 7% . Early endocarditis occurred in two of the 1,022 patient cohort, and freedom from late infection (34 patients) actuarially at 20 years was 89% . One-third of these patients were medically cured of their endocarditis . Preservation methods (4 degrees C or cryopreservation) and implantation techniques displayed no difference in the overall actuarial 20-year incidence of late survival endocarditis, thromboembolism or structural degeneration requiring operation . Thromboembolism occurred in 55 patients (35 permanent, 20 transient) with an actuarial 15-year freedom in the 861 patients having aortic valve replacement +/- CABG surgery of 92% and in the 105 patients having additional mitral valve surgery of 75% (p = 0.000) . Freedom from reoperation from all causes was 50% at 20 years and was independent of valve preservation . Freedom from reoperation for structural deterioration was very patient age-dependent . For all cryopreserved valves, at 15 years, the freedom was 47% (0-20-year-old patients at operation), 85% (21-40 years), 81% (41-60 years) and 94% (>60 years) . Root replacement versus subcoronary implantation reduced the technical causes for reoperation and re-replacement (p = 0.0098) . CONCLUSION: This largest, longest and most complete follow up demonstrates the excellent advantages of the homograft aortic valve for the treatment of acute endocarditis and for use in the 20+ year-old patient . However, young patients (< or = 20 years) experienced only a 47% freedom from reoperation from structural degeneration at 10 years such that alternative valve devices are indicated in this age group . The overall position of the homograft in relationship to other devices is presented.

Acta Med Croatica, 2000, 54(4-5), 165 - 73
Hepatorenal syndrome: new perspectives in pathophysiology and management; Kes P; Hepatorenal syndrome (HRS) is a unique form of acute renal failure occurring in patients with advanced liver disease . Despite the severe derangement of renal function and ominous prognosis, minimal pathologic abnormalities of the kidneys are found at autopsy . The kidneys, if transplanted, are capable of normal function, which supports the concept that renal failure is functional and potentially reversible . The pathogenesis of HRS is not completely known, but it is probably the result of an extreme underfilling of the arterial circulation secondary to an arterial vasodilation located in splanchnic circulation . Besides the renal circulation, all other extrasplanchnic vascular beds also appear to be vasoconstricted . The diagnosis of HRS is currently based on several widely accepted diagnostic criteria aimed at excluding nonfunctional causes of renal failure . Recently initiated therapeutic approaches lend a note of optimism to the future management of HRS . These include liver transplantation as definitive treatment for patients with end-stage liver disease, and introduction of new vasoconstrictor drugs with the preferential effect on the splanchnic circulation . The development of HRS after spontaneous bacterial peritonitis may be effectively prevented by the administration of albumin together with antibiotic therapy.

J Clin Virol, 2001 May, 21(2), 105 - 17
Rapid multiserotype detection of human rhinoviruses on optically coated silicon surfaces; Ostroff R et al.; BACKGROUND: More than 100 immunologically distinct serotypes of human rhinoviruses (HRV) have been discovered, making detection of surface exposed capsid antigens impractical . However, the non-structural protein 3C protease (3Cpro) is essential for viral replication and is relatively highly conserved among serotypes, making it a potential target for diagnostic testing . The thin film biosensor is an assay platform that can be formatted into a sensitive immunoassay for viral proteins in clinical specimens . The technology utilizes an optically coated silicon surface to convert specific molecular binding events into visual color changes by altering the reflective properties of light through molecular thin films . OBJECTIVE: To develop a rapid test for detection of HRV by developing broadly serotype reactive antibodies to 3Cpro and utilizing them in the thin film biosensor format . STUDY DESIGN: Polyclonal antibodies to 3Cpro were purified and incorporated into the thin film assay . The in vitro sensitivity, specificity and multiserotype cross-reactivity of the 3Cpro assay were tested . Nasal washes from naturally infected individuals were also tested to verify that 3Cpro was detectable in clinical specimens . RESULTS: The 3Cpro assay is a 28-min, non-instrumented room temperature test with a visual limit of detection of 12 pM (picomolar) 3Cpro . In terms of viral titer, as few as 1000 TCID(50) equivalents of HRV2 were detectable . The assay detected 45/52 (87%) of the HRV serotypes tested but showed no cross-reactivity to common respiratory viruses or bacteria . The thin film assay detected 3Cpro in HRV-infected cell culture supernatants coincident with first appearance of cytopathic effect . Data are also presented demonstrating 3Cpro detection from clinical samples collected from HRV-infected individuals . The assay detected 3Cpro in expelled nasal secretions from a symptomatic individual on the first day of illness . In addition, 9/11 (82%) concentrated nasal wash specimens from HRV infected children were positive in the 3Cpro test . CONCLUSION: We have described a novel, sensitive thin film biosensor for rapid detection of HRV 3Cpro . This test may be suitable for the point of care setting, where rapid HRV diagnostic test results could contribute to clinical decisions regarding appropriate antibiotic or antiviral therapy.

Transplantation, 2001 Apr 27, 71(8), 1172 - 5
Helicobacter pylori-associated gastric MALT lymphoma in liver transplant recipients; Shehab TM et al.; BACKGROUND: Immunosuppressed transplant recipients are at increased risk of developing several forms of malignancy . The aim of this study is to report the clinical presentation, treatment, and outcome of four liver transplant recipients with Helicobacter pylori-associated gastric mucosae-associated lymphoid tissue (MALT) lymphoma . METHODS: The medical records of four liver transplant recipients with gastric MALT lymphoma were reviewed . In situ hybridization for Epstein-Barr-encoded ribonucleic acid was performed on formalin-fixed tissues . RESULTS: All four subjects presented with abdominal symptoms at a mean of 6.1 years posttransplant . Ulcerative lesions biopsied at endoscopy demonstrated early-stage gastric MALT lymphoma with associated Helicobacter pylori gastritis . In situ hybridization revealed no evidence of Epstein-Barr virus infection in examined tissues . Antibiotic eradication of Helicobacter pylori lead to disease remission in three subjects with a mean follow-up of 21 months, and one subject failed to respond to antibiotics and radiation therapy and died from metastatic gastric adenocarcinoma . CONCLUSIONS: Early-stage, low-grade gastric MALT lymphoma that was associated with Helicobacter pylori gastritis responded to antibiotic therapy with a sustained clinical remission in three of four treated subjects . If other studies confirm a higher than expected incidence of gastric MALT lymphoma in immunosuppressed transplant recipients with Helicobacter pylori infection, screening and treating Helicobacter pylori infection in selected transplant patients may prove beneficial.

Clin Tech Small Anim Pract, 2001 Feb, 16(1), 13 - 6
Ocular pharmacology; Champagne ES; Many new drugs come on the market each year, and some very useful ones become unavailable . Medical treatment of some of the more common ophthalmic conditions observed in small animal practice are discussed in this article . Selection of the appropriate antibiotic or antiviral is critical for effective treatment, and indications for these drugs are provided . Anti-inflammatory medications and their indications and contraindications are also discussed . Medical therapy of glaucoma is also addressed.

Rev Pneumol Clin, 2001 Feb, 57(1 Pt 1), 32 - 4
{Acute respiratory failure responsive to cotrimoxazole and corticosteroïds in an AIDS patient}; Thomas F et al.; We report a case of acute respiratory failure due to Toxoplasma gondii mimicking pneumocystosis in an AIDS patient . Empirical antibiotic therapy with cotrimoxazole is discussed . Active research and identification of pathogens with adapted laboratory tests is mandatory.

Instr Course Lect, 2001, 50, 367 - 77
Revision total knee arthroplasty: planning, controversies, and management--infection; Munjal S et al.; Routine blood work that includes ESR, CRP, and glucose levels, and plain radiographs and knee aspirations are obtained from our patients who have clinical suspicion of infection . If the culture result is positive and blood tests suggest infection, the surgical plan is a two-stage revision with an interval period of intravenous antibiotic administration . Risk factors are identified, and the patient's condition optimized . An infectious disease consultant is also involved in the treatment care plan and advises the patient about the best antibiotic, management of proper antibiotic levels, and home care . If culture results are negative, cultures are repeated every week for 3 to 4 weeks after the patient stops taking antibiotics . If the cultures yield positive results, a two-stage revision protocol is initiated . In patients who have 3 to 4 negative culture results, normal blood tests and radiographs, and no history of any immunocompromised state, such as diabetes or rheumatoid arthritis, diagnoses such as polyethylene wear or synovitis can be considered . If patients have any involved risk factor or blood tests, equivocal or suggestive, isotope scintigraphy is requested . We examine tissue in patients with positive scans and equivocal blood test results with clinical suspicion of infection . We prefer an open arthrotomy, which allows us to take multiple specimens for frozen section, assess fixation of the implant, and look for any other signs of infection . If the frozen section reveals more than 10 PMNLs per high-power field, we proceed to stage 1 revision after obtaining intraoperative cultures . If an organism grows in the cultures, stage 2 protocol is initiated . If no cultures are obtained at 7 to 10 days of incubation, we may consider earlier stage 2 revision at 4 to 6 weeks (Fig . 1) . In patients in whom the frozen section reveals less than 5 PMNLs per high-power field, component fixation should be assessed, and if they are loose, revision of the knee should be initiated . As with a septic revision, use of antibiotic-impregnated cement can be considered for fixation . If the components are well fixed, a polyethylene tibial tray is exchanged . In either circumstance, intraoperative cultures should be obtained, and if they yield positive results, antibiotics should be continued for 6 to 12 weeks.

Ann Surg, 2001 Jun, 233(6), 740 - 51
A prospective comparison of simultaneous kidney-pancreas transplantation with systemic-enteric versus portal-enteric drainage; Stratta RJ et al.; OBJECTIVE: To compare pancreas transplantation with systemic-enteric (SE) versus portal-enteric (PE) drainage in a prospective fashion . SUMMARY BACKGROUND DATA: To improve the physiology of pancreas transplantation, the authors developed a new technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions . METHODS: During a 26-month period, the authors prospectively alternated 54 consecutive simultaneous kidney and pancreas transplants to either SE (n = 27) or PE (n = 27) drainage . The two groups were well matched for numerous characteristics . Maintenance immunosuppression in both groups consisted of tacrolimus, mycophenolate mofetil, and steroids . RESULTS: Patient survival rates were 93% SE versus 96% PE; kidney graft survival rates were 93% in both groups . Pancreas transplantation survival (complete insulin independence) was 74% after SE versus 85% after PE drainage with a mean follow-up of 17 months . The mean length of initial hospital stay was 12.4 days in the SE group and 12.8 days in the PE group . The SE group was characterized by a slight increase in the number of readmissions . The incidences of acute rejection (33%) and major infection (52%) were similar in both groups . The incidence of intraabdominal infection was slightly higher in the SE group . However, the early relaparotomy rate was similar between groups . The composite endpoint of no rejection, graft loss, or death was attained in 56% of SE versus 59% of PE patients . CONCLUSIONS: These results suggest that simultaneous kidney and pancreas transplantation with SE or PE drainage can be performed with comparable short-term outcomes.

Lakartidningen, 2001 Apr 18, 98(16), 1899 - 903
{Prophylactic and empirical treatment of mycoses in neutropenic fever . Report and comments on meta-analysis}; Kalin M et al.; Patients treated for cancer with chemotherapy and other cytoreductive therapy often develop serious bacterial, viral, and fungal infections due to B- and T-cell depletion, neutropenia and decreased barrier function of mucosal membranes . In patients with neutropenic fever not responding to broad spectrum antibiotic therapy there is a high risk of fungal infection . In a Cochrane Library meta-analysis of the effect of prophylactic and empirical antifungal treatment, amphotericin B was found to be the only drug affecting total mortality . Fluconazole, ketoconazole and itraconazole affected risk of colonization and invasive infection, but not the total risk of death . We agree with these conclusions, but emphasize that the appropriate time to initiate empirical antifungal therapy is still not settled . We also believe that azoles may be of value in the therapy of symptomatic mucositis.

Biotechnol Bioeng, 2001 Jul 20, 74(2), 154 - 63
Novel pristinamycin-responsive expression systems for plant cells; Frey AD et al.; Novel gene regulation systems were designed for plant cells responsive to the streptogramin antibiotic pristinamycin . The pristinamycin-repressible plant gene regulation concept (PIPpOFF) is based on a transcriptional activator (PIT) which consists of the Pip protein, the repressor of the pristinamycin resistance operon of Streptomyces coelicolor, fused to the VP16 transactivation domain of the Herpes simplex virus . PIT mediates pristinamycin-repressible activation of a synthetic plant promoter (P(pPIR)) in tobacco cells consisting of a nine Pip-binding site-containing artificial operator (PIR3) placed upstream of a TATA-box derived from the cauliflower mosaic virus 35S promoter (P(CaMV35S)) . Pristinamycin interferes with induction by negatively regulating the DNA-binding capacity of the Pip moiety of PIT . A second, streptogramin-inducible plant gene regulation system (PIPpON) was constructed by combining Pip expression with a plant-specific pristinamycin-inducible promoter (P(pPIRON)) . P(pPIRON) consists of a PIR3 module cloned downstream of the strong constitutive plant promoter P(CaMV35S) . As in the native Streptomyces configuration, Pip binds to its cognate sequence within P(pPIRON) in the absence of regulating antibiotic and silences the chimeric plant promoter . Upon addition of pristinamycin, Pip is released from the PIR3 operator and full P(CaMV35S)-driven expression of desired plant genes is induced . The PIPpOFF and PIPpON systems performed well in Nicotiana tabacum suspension cultures and promise to provide an attractive extension of existing plant gene regulation technology for basic plant research or biopharmaceutical manufacturing using plant tissue culture . Copyright John Wiley & Sons, Inc.

Saudi Med J, 2000 Oct, 21(10), 979 - 82
Hemophagocytic syndrome; Al-Talag AH et al.; This case report is about an elderly man who presented with a long-standing history of high-grade fever and weight loss . He initially had only hepatosplenomegaly, but then developed jaundice . He also had pancytopenia and raised liver enzymes . His septic screen was negative, but he had a positive Monospot test and immunoglobulin G for Epstein-Barr virus . The liver biopsy showed sinusoidal phagocytosis and the subsequent bone marrow aspiration and biopsy showed significant hemophagocytosis, hence Hemophagocytic syndrome was diagnosed . The fever was refractory to antibiotic and anti-tuberculosis therapy, but it responded only partially to steroids . Full response was only noticed following anti-viral treatment in the form of intravenous Ganciclovir . The patient's general condition, liver enzymes, bilirubin, hematological parameters and even the weight returned back to their normal range 2 weeks after Ganciclovir therapy . Cessation of this drug resulted in relapse of his symptoms and oral antivirals did not help . Splenectomy, steroid pulse therapy and immunosuppressive treatment were only partially helpful . Reintroduction of Ganciclovir did help for a short period . We conclude that our patient had virus-associated hemophagocytic syndrome most likely related to Epstein-Barr virus infection, which was then confirmed by the splenic biopsy, and that Ganciclovir can be of great help in eradicating the virus and treating the disease, provided that it is given for a long enough period.

J Am Acad Dermatol, 2001 Jun, 44(6), 995 - 8
Tacrolimus ointment for the treatment of steroid-induced rosacea: a preliminary report; Goldman D; BACKGROUND: Excessive topical corticosteroid application to facial areas commonly leads to steroid-induced rosacea . This may be a recalcitrant problem that requires months of antibiotic and anti-inflammatory therapy before it resolves . OBJECTIVE: The purpose of this article is to review the use of tacrolimus ointment, a macrolide anti-inflammatory ointment for the treatment of 3 patients with steroid-induced rosacea . METHODS: Three patients with steroid-induced rosacea applied tacrolimus ointment, 0.075% twice daily for 7 to 10 days . Patients were also instructed to avoid topical corticosteroid use and other rosacea-aggravating substances including caffeine, spicy foods, alcohol, hot fluids, and fluoride . Patients were observed for tenderness, erythema, and relief of pruritus . RESULTS: Pruritus, tenderness, and erythema were resolved in all 3 patients after 7 to 10 consecutive days' use of tacrolimus 0.075% ointment in conjunction with avoidance of topical steroids, caffeine, spicy food, alcohol, hot fluids, and fluoride . CONCLUSION: This preliminary study demonstrates that tacrolimus 0.075% ointment may be effective for patients with steroid-induced rosacea, when combined with avoidance of topical steroid use, as well as avoidance of other agents known to aggravate rosacea (caffeine, spicy foods, alcohol, hot fluids, and fluoride).

Reprod Nutr Dev, 2001 Jan-Feb, 41(1), 41 - 6
Preliminary study on the requirements of Entodinium exiguum and E . caudatum for live or dead bacteria when cultured in vitro; Fondevila M et al.; Whether live bacteria are required to culture the rumen protozoa Entodinium exiguum and E . caudatum in vitro was studied . Treatments were protozoa plus antibiotics (PA), PA plus autoclaved bacteria (PAB) or protozoa plus live bacteria (PLB) . Generation times at 24 h were 22.8 and 31.0 h for E . exiguum and E . caudatum . Protozoal concentrations were unaffected by the absence of bacteria up to 48 h . After 72 h, E . exiguum, concentrations were higher in PLB than PA or PAB . With E . caudatum differences between PLB and PA were only observed at 96 h . Thus, a requirement for live bacteria appears to be manifested in culture periods longer than 48 (E . exiguum) and 72 (E . caudatum) h . Although differences between PLB and PAB indicate a metabolic dependence for bacteria or a long-term antibiotic effect, non-significant differences between PAB and PA suggest that the effect is also related to a nutritive bacterial contribution.

BETA, 1999 Jan, 12(1), 33 - 41
Opportunistic infections...is it safe to stop prophylaxis?
Highleyman L.
AIDS: An opportunistic infection (OI) rarely affects people with healthy immune systems, but can be life-threatening to people whose immune systems are weakened by HIV . Prophylaxis is the use of drugs to prevent the occurrence or recurrence of a disease, such as an OI . Since the use of highly active antiretroviral therapy (HAART), OI incidence and progression, hospitalization, and AIDS-related deaths have declined . This treatment may be even more effective than specific OI prophylaxis regimens . The value of HAART in treating HIV and acting as a preventative regimen against OIs are discussed . Antiretroviral use may allow people with HIV to discontinue their OI prophylaxis . Discontinuing prophylaxis has many benefits, including a reduction in the large numbers of medications HIV-infected people must take . A summary of common OIs, symptoms, and treatment is provided .

Body Posit, 1999 Jul, 12(7), 9 - 10
Stopping preventive treatments; Fornataro K et al.; AIDS: Although combination therapy with HAART (Highly Active AntiRetroviral Therapy) can increase CD4 (T-cell) counts, doctors have been cautious about stopping preventive treatments, or prophylaxis, for PCP (Pneumocystis carinii pneumonitis) . Two studies, however, suggest that if HAART increases T-cell counts to over 200 for an extended time period, PCP prophylaxis may be safely stopped . Partly as a result of these study findings, the United States Public Health Service has rewritten guidelines on the prevention of opportunistic infections . The draft version continues to call for PCP prevention beginning when patients have T-cell counts below 200 or have a history of thrush . However, a new section states that providers may stop prophylactic treatment when T-cell counts remain over 200 for at least three to six months . Recommendations for preventing MAC (mycobacterium avium complex) and CMV (cytomegalovirus) have also changed with HAART and are briefly described .

GMHC Treat Issues, 1999 Apr, 13(4), 4 - 5
Stopping PCP prophylaxis after suppressing HIV; Norton M; AIDS: There is mounting evidence that AIDS patients on successful therapy may be able to stop taking prophylactic drugs for opportunistic infections (OIs) . Draft revisions of the U.S . Public Health Service=s AGuidelines for the Prevention of Opportunistic Infections@ urges stopping primary PCP prophylaxis in people whose CD4 counts increase to above 200 cells/mm3 for at least 3 to 6 months . Results of the EuroSIDA study of 7,333 patients from across Europe and Israel show that people with rebounding CD4 counts can tolerate discontinuation of PCP prophylaxis . Results of other studies supporting this conclusion are briefly reviewed . Summary results from EuroSIDA, Swiss, and Dutch studies are presented in table form . Issues still remain regarding PCP prophylaxis, however, including brief study follow-ups, lack of controlled clinical trials and questions surrounding secondary prophylaxis .

AIDS Policy Law . 1999 Apr 30;14(8):1, 9.
Jury says dentist did not regard patient as HIV-positive; Protect yourself from Pneumocystis carinii; AIDS: The Centers for Disease Control and Prevention (CDC) has determined that HIV-infected people are more likely to become infected first with Pneumocystis carinii pneumonia (PCP) than any other opportunistic infection . About 53 percent of people who died of AIDS between 1992 and 1997 had PCP . The symptoms of the disease are fever, cough, and breathing problems . PCP is thought to be spread through the air - and not through sexual transmission - so it is difficult to prevent exposure . There is no vaccine against PCP, so the most effective treatment is TMP-SMX, a drug which can prevent PCP . The effects and treatment of PCP in adults and children are described, and contact information is provided .

Hopkins HIV Rep . 1999 Mar;11(2):2, 7, 12.
Opportunistic infections: down but not out; Bishai WR et al.; AIDS: While the 6th Conference on Retroviruses and Opportunistic Infections focused heavily on HIV therapies and their complications, issues related to opportunistic infections (OIs) continued to draw attention . The dramatic reduction in OIs in the HAART era and evidence supporting the discontinuation of OI prophylaxis were discussed . Studies related to Pneumocystis carinii pneumonia (PCP), MAC and TB, CMV, and Kaposi's sarcoma (KS) were presented . OIs continue to be a major area of concern in developing countries, where drug therapies are often too expensive to be practical . Prophylaxis against bacterial infections and TB offer the best hope for prolonging life in those countries .

Fac Notes (New Orleans La), 1998 Jan-Feb, 10(1), 5 - 6
Update: prophylaxis for HIV opportunistic infections; Murphy MJ; AIDS: The U.S . Public Health Service and the Infectious Diseases Society of America recently updated the 1995 guidelines on prevention of opportunistic infections in HIV infected individuals . PCP prophylaxis has not been changed in the new guidelines . Primary prevention strategies for toxoplasmosis encephalitis are described . Preventive medication for tuberculosis is generally not recommended, especially for persons in high risk groups such as the homeless and injection drug users . Significant changes were made for the prevention of Mycobacterium avium complex (MAC), and guidelines were changed for preventing bacterial respiratory infections . Primary prophylaxis of most fungal infections is generally not recommended, but lifelong secondary prophylaxis is indicated for all deep seated fungal infections and CMV . Prevention of opportunistic infections in HIV patients has a significant impact on morbidity and mortality .

NIAID AIDS Agenda . 1996 Sep;:4-5.
CPCRA researchers present OI studies at Vancouver; Bowersox J; AIDS: The Community Programs for Clinical Research on AIDS (CPCRA) presented several recent findings from clinical trials at the International Conference on AIDS . Weekly doses of fluconazole can safely prevent persistent yeast infections in HIV-infected women who frequently develop yeast infections of the mouth, vagina and throat . Combination antibiotic therapy given intermittently is an effective initial treatment for persons with HIV-related tuberculosis . High dosages of clarithromycin should not be given to patients with Mycobacterium avium complex (MAC); doses above 500 mg are associated with higher mortality levels . Researchers have also determined the genetic sequence of the virus that causes molluscum contagiosum, a skin disease affecting up to 18 percent of AIDS patients .

AIDS Clin Care . 1996 Jan;8(1):7, 10.
Severe sore throat in a patient with AIDS; Zuger A; AIDS: A case of a 45-year-old HIV-infected male who developed a severe throat infection with serious complications is reported . Despite a low CD4 count, the patient suffered only one significant illness in ten years since his diagnosed HIV infection . Overly aggressive antibiotic therapy caused fungal and thrush infections, leading to dehydration and extreme weight loss . The patient was treated with rehydration therapy, antifungal agents, and TMP-SMX, after which other complications, including multiple infections and B-cell lymphoma, were diagnosed . He refused chemotherapy after one course of treatment and was sent home with hospice care .

AIDS Policy Law, 1995 Aug 11, 10(14), 4 - 5
Arbitration seen as inappropriate in denial-of-care claim; Abbott files SNDA for MAC prophylaxis; AIDS: Clinical results suggest that clarithromycin may be effective in preventing the onset of disseminated Mycobacterium avium complex (MAC) . Among 667 patients treated with clarithromycin, the incidence of disseminated MAC was reduced 69 percent by using the antibiotic prophylactically . Mortality from all causes over the 2-year period of the study was reduced by 28 percent among those receiving clarithromycin compared to those receiving placebo . The prophylactic regimen was well tolerated with the only side effect being taste perversion . These results have prompted Abbott Laboratories to request the Food and Drug Administration (FDA) to approve the drug for this use .

AIDS Treat News, 1995 Jun 2, (no 224), 1 - 4
Diarrhea, and the experimental treatment Saccharomyces boulardii; James JS; AIDS: Saccharomyces boulardii (S . boulardii), a live yeast, has been shown to be a safe and useful treatment for HIV-related diarrhea . Although the mechanism of action is uncertain, researchers believe it may reduce inflammation or increase immune responses in the blood . However, the yeast may take advantage of an immune deficiency and cause a systemic infection . Other trials have studied S . boulardii for treatment or prevention of diarrhea due to various causes unrelated to HIV, such as antibiotic-associated diarrhea and Crohn's disease . Researchers found statistically significant benefit of S . boulardii in reducing diarrhea in many of these studies . At least two different S . boulardii products are available in AIDS buyers' clubs today . Laboratoires Biocodex, the French company now running clinical trials of S . boulardii, markets a lyophilized (freeze-dried) form of the yeast in Europe, South America, and Africa . Jarrow Formulas, a competitor, sells a less expensive S . boulardii product . For now, patients must rely largely on anecdotal and imprecise studies for information on how to use the treatment, since most of the clinical trials have been with HIV-negative patients . According to one buyer's club, most people start with three grams a day, and then work down to one gram a day to control the diarrhea .

Notes Undergr, 1995 Winter, (no 29), 3 - 4
Roxithromycin; Pelvic inflammatory disease in women infected with HIV; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, USAPelvic inflammatory disease (PID) and HIV infection are frequently coincident . The diagnosis of PID can be more difficult to make in HIV-infected than in uninfected women . In general, HIV-infected women with PID have a good response to standard intravenous antibiotic therapy . However, surgical therapy is more frequently required for HIV-infected women with PID, especially those with more severe degrees of immunosuppression, than for uninfected women.

J Clin Pharmacol, 2001 May, 41(5), 563 - 72
Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr; Hendershot PE et al.; Linezolid is a novel oxazolidinone antibiotic with mild reversible monoamine oxidase inhibitor (MAOI) activity . The potential for interaction with over-the-counter (OTC) medications requires quantification . The authors present data evaluating the pharmacokinetic and pharmacodynamic responses to coadministration of oral linezolid with sympathomimetics (pseudoephedrine and phenylpropanolamine) and a serotonin reuptake inhibitor (dextromethorphan) . Following coadministration with linezolid, minimal but statistically significant increases were observed in pseudoephedrine and phenylpropanolamine plasma concentrations; a minimal but statistically significant decrease was observed in dextrorphan (the primary metabolite of dextromethorphan) plasma concentrations . Increased blood pressure (BP) was observed following the coadministration of linezolid with either pseudoephedrine or phenylpropanolamine; no significant effects were observed with dextromethorphan . None of these coadministered drugs had a significant effect on linezolid pharmacokinetics . Minimal numbers of adverse events were reported . Potentiation of sympathomimetic activity by linezolid was judged not to be clinically significant, but patients sensitive to the effects of increased BP due to predisposing factors should be treated cautiously . No restrictions are indicated for the coadministration of dextromethorphan and linezolid.

J Immunol, 2001 Jun 1, 166(11), 6545 - 54
Molecular identification of IgE-dependent histamine-releasing factor as a B cell growth factor; Kang HS et al.; The culture supernatants of LK1 cells, murine erythroleukemia cells, showed B cell-stimulating activity . Purification and NH(2)-terminal sequence analysis revealed that one of the candidates was murine IgE-dependent histamine-releasing factor (IgE-HRF), which is known to induce histamine from basophils . Recombinant IgE-HRF (rHRF) obtained from Escherichia coli- or 293-transformed embryonal kidney cells was tested for B cell-stimulating activity . Both rHRFs stimulated B cell proliferation in a dose-dependent manner . However, boiling or anti-HRF Ab abolished the B cell stimulatory effects of rHRF . Recombinant HRF showed strong synergistic effects with IL-2, IL-4, and IL-5 for B cell activation, with maximal activity in the presence of anti-CD40 AB: Recombinant HRF increased MHC class II expression of B cells . It also increased Ig production from B cells . Treatment with polymyxin B, a neutralizing peptide antibiotic of LPS, did not reduce the activity of rHRF . In addition, FACS analysis using PE-conjugated rHRF showed that HRF bound to B cells . Recombinant HRF up-regulated the expression of IL-1 and IL-6 in B cells . In vivo administration of rHRF or the cDNA for rHRF increased total and Ag-specific Ig synthesis . Taken together, these results indicate that HRF stimulates B cell activation and function.

Mol Microbiol, 2001 May, 40(3), 530 - 41
Analysis of temporal and spatial expression of the CcaR regulatory element in the cephamycin C biosynthetic pathway using green fluorescent protein; Kyung YS et al.; The DNA-binding capability of a key secondary metabolite regulatory element (CcaR) in the Streptomyces clavuligerus cephamycin C pathway was investigated by gel mobility retardation and DNase I footprinting analysis . These results revealed that CcaR specifically binds to the promoter region of the lysine-epsilon-aminotransferase gene (lat) . Green fluorescent protein (GFP) was subsequently used as a reporter to analyse in vivo expression of CcaR . The corresponding isogenic strain containing ccaR:gfp in the chromosome produced cephamycin C at levels similar to those of wild-type S . clavuligerus . Confocal laser scanning microscopy revealed that expression of CcaR in liquid culture was temporally dynamic and spatially heterogeneous in S . clavuligerus mycelia . The highly fluorescent seed culture mycelia quickly lost fluorescence upon inoculation into fresh culture medium . The characteristic green colour reappeared in a small portion of mycelia during mid-exponential growth phase . As the culture aged, the population expressing CcaR expanded, and the expression level increased . This was followed by a reduction in the CcaR-expressing population towards the end of the culture period . During peak expression, CcaR was distributed uniformly in mycelia, but became localized distal to the chromosome when the culture entered stationary phase . In solid phase analysis, abundant CcaR expression was evident in the substrate mycelia, but was completely absent in aerial hyphae . These results show regulatory linkage between ccaR and lat, whose expression profile showed a similar spatial decoupling between morphogenesis and antibiotic production . In addition, visualizing CcaR within S . clavuligerus mycelia demonstrates a distinct pattern of localization over the course of physiological differentiation.

Best Pract Res Clin Obstet Gynaecol, 2001 Feb, 15(1), 49 - 61
Physical sequelae of caesarean section; Jackson N et al.; The complications and recovery from caesarean section are dominated by the medical condition of the woman pre-operatively . Evidence regarding risks directly attributable to the caesarean section is scanty, and often derived from obstetric practice that differs from the current day . Mortality associated with the procedure is anything up to five times that for vaginal delivery, with emergency caesarean section associated with almost twice the risk of elective procedures . Data regarding placenta praevia and placenta praevia-accreta come from population series where antibiotics were not routinely used for caesarean section, but there is no doubt that previous caesarean section increases the risk of both . Antibiotic and thromboprophylaxis at the time of caesarean section decrease morbidity in the index pregnancy, but can also reasonably be expected to reduce future pregnancy complications .

Best Pract Res Clin Obstet Gynaecol, 2001 Feb, 15(1), 17 - 47
Techniques for performing caesarean section; Hema KR et al.; In many countries caesarean section has become the mode of delivery in over a quarter of all births . Safety of the mother and cost are the two main areas of concern . Various studies on the techniques of performing a caesarean section have focused on reducing the operating time, blood loss, wound infection and cost . Given the fact that caesarean section is the most commonly performed operation in obstetrics, it is important that trainers and trainees are familiar with the basic surgical techniques and that best practice is followed . At the same time surgeons should take necessary precautions to reduce their risk of exposure to Hepatitis B and HIV.The skin incision and entry into abdominal cavity is best achieved by the modified Cohen's incision . The lower segment transverse uterine incision has stood the test of time over a period of 75 years and remains the best way to enter the uterus . Closure of the uterus in single layer appears to be acceptable, whenever technically possible . Placental delivery should be by controlled cord traction after spontaneous expulsion . Closure of the visceral and parietal layers of the peritoneum no longer seems to be necessary . Obliteration of space in the subcutaneous layer, either by suture or by suction, seems to reduce wound disruption . These issues are being considered in the CAESAR randomized controlled trial of surgical techniques currently underway in England.Prophylactic antibiotics are mandatory in preventing post-operative morbidity . Many of the above mentioned steps have been tested in randomized trials . Further studies are needed to examine a wide range of questions arising from this review, e.g . best position of the patient, the value of exteriorization of the uterus whilst repairing the uterus, and the use of agents to relax the uterus in difficult deliveries .

Cancer Res, 2001 May 15, 61(10), 4024 - 9
Clinical concentrations of doxorubicin inhibit activity of myocardial membrane-associated, calcium-independent phospholipase A(2); McHowat J et al.; Use of the anticancer antibiotic doxorubicin continues to be limited by its cumulative dose-related cardiotoxicity . Our study reports inhibition of myocardial intracellular calcium-independent phospholipase A(2) (iPLA(2)) activity by clinically relevant concentrations of the drug . The effect was first shown in vitro using suspensions of freshly isolated rat and rabbit cardiomyocytes . Addition of 0.1-10 microM doxorubicin to these cells led to a concentration- and time-dependent inhibition of total iPLA(2), as measured using (16:0, {(3)H}18:1) plasmenylcholine and phosphatidylcholine substrates in the presence or absence of calcium . Subcellular fractionation into cytosolic and membrane fraction revealed that the drug selectively inhibits membrane-associated iPLA(2) activity, without altering activity of the cytosolic enzyme . Doxorubicin treatment of cells prelabeled with {H(3)}arachidonic acid led to a depression of baseline arachidonic acid release levels, corroborating iPLA(2) inhibition . Reducing agents blocked PLA(2) inhibition in cardiomyocyte suspensions, suggesting that the doxorubicin effect is mediated by oxidation of susceptible cysteines . In vivo experiments, in which adults rats were i.v . injected with a bolus dose of 4 mg/kg doxorubicin, confirmed in vitro findings, revealing a 2-fold decrease in membrane-associated Ca(2+)-independent iPLA(2) activity in the heart tissue of treated animals . The observed phenomenon has important implications for myocyte signaling cascades and membrane remodeling.

Cancer Res, 2001 May 15, 61(10), 4010 - 6
Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin; Yang J et al.; Glioblastoma multiforme is the most treatment-resistant brain tumor . Elongation factor-2 (EF-2) kinase (calmodulin kinase III) is a unique protein kinase that is overexpressed in glioma cell lines and in human surgical specimens . Several mitogens activate this kinase and inhibitors block mitogen activation and produce cell death . Geldanamycin (GA) is a benzoquinone ansamycin antibiotic that disrupts Hsp90-protein interactions . Because EF-2 kinase is chaperoned by Hsp90, we investigated the effects of GA on the viability of glioma cells, the expression of EF-2 kinase protein, and the interaction between Hsp90 and EF-2 kinase . GA was a potent inhibitor of the clonogenicity of four glioma cells lines with IC(50)s ranging from 1 to 3 nM . 17-allylamino-17-demethoxygeldanamycin (17-AAG), a less toxic and less potent derivative of GA, inhibited the clonogenicity of glioma cells with IC(50) values of 13 nM in C6 cells and 35 nM in T98G cells . Treatment of cell lines for 24-48 h of GA or 17-AAG disrupted EF-2-kinase/Hsp90 interactions as measured by coimmunoprecipitation, resulting in a decreased amount of recoverable kinase in cell lysates . The ability of GA to inhibit the growth of glioma cells was abrogated by overexpressing EF-2 kinase . In addition, 17-AAG significantly inhibited the growth of a glioma xenograft in nude mice . These studies demonstrate for the first time the activity of GAs against human gliomas in vitro and in vivo and suggest that destruction of EF-2 kinase may be an important cytotoxic mechanism of this unique class of drug.

Microbes Infect, 2001 Mar, 3(3), 231 - 5
The role of non-biting flies in the epidemiology of human infectious diseases; Graczyk TK et al.; The feeding and reproductive habits of non-biting synanthropic flies make them important mechanical vectors of human pathogens . Synanthropic flies are major epidemiologic factors responsible for the spread of acute gastroenteritis and trachoma among infants and young children in (predominantly) developing countries . House flies are involved in mechanical transmission of nosocomial infections with multiple antibiotic-resistant bacteria in hospital environments.

J Chromatogr A, 2001 Apr 20, 914(1-2), 53 - 8
Liquid chromatography of troleandomycin; Chepkwony HK et al.; Until now no liquid chromatography (LC) method is described to determine the purity and content of troleandomycin and its related substances . A simple, robust, sensitive and selective isocratic liquid chromatographic method suitable for the determination of the antibiotic troleandomycin and its related substances is described . This method utilizes as a stationary phase: XTerra RP18 5 microm (25 cm x 4.6 mm I.D.) at 30 degrees C and as mobile phase: acetonitrile-0.2 M ammonium acetate buffer (pH 6.0)-water (45:5:50, v/v), delivered at a flow-rate of 1.0 ml/min . UV detection is performed at 205 nm . Troleandomycin is separated from the partially acetylated related substances and from several unknown impurities present in commercial samples . The robustness of the method was evaluated by a full-factorial experimental design.

Can J Microbiol, 2001 Apr, 47(4), 332 - 40
Competition and antibiosis in the biological control of potato scab; Neeno-Eckwall EC et al.; Nonpathogenic, antibiotic-producing streptomycetes have been shown to reduce potato scab when added to disease-conducive soil . Spontaneous mutants of the pathogenic Streptomyces scabies RB4 that are resistant to at least one antibiotic activity produced by the nonpathogenic suppressive isolates Streptomyces diastatochromogenes strain PonSSII and S . scabies PonR have been isolated . To determine the importance of antibiosis in this biocontrol system, these mutants were investigated for their ability to cause disease in the presence of the two pathogen antagonists in a greenhouse assay . Disease caused by one of the mutant strains was reduced in the presence of both suppressive isolates, whereas disease caused by the other five mutants was not significantly reduced by either suppressive strain . In addition, a nonpathogenic mutant of S . scabies RB4 was isolated, which produced no detectable in vitro antibiotic activity and reduced disease caused by its pathogenic parent strain when the pathogen and mutant were coinoculated into soil . Population densities of the pathogen were consistently lower than those of the suppressive strains when individual strains were inoculated into soil . When a pathogen was coinoculated with a suppressive strain, the total streptomycete population density in the pot was always less than that observed when the suppressive isolate was inoculated alone . When the pathogens were inoculated individually into soil, a positive correlation was seen between population density and disease severity . In coinoculation experiments with pathogen and suppressive strains, higher total streptomycete population densities were correlated with lower amounts of disease.

Bioorg Med Chem, 2001 Apr, 9(4), 815 - 24
Synthetic mannosides act as acceptors for mycobacterial alpha1-6 mannosyltransferase; Brown JR et al.; A series of synthetic mannosides was screened in a cell-free system for their ability to act as acceptor substrates for mycobacterial mannosyltransferases . Evaluation of these compounds demonstrated the incorporation of {14C}Man from GDP-{14C}Man into a radiolabeled organic-soluble fraction and analysis by thin layer chromatography and autoradiography revealed the formation of two radiolabeled products . Each synthetic acceptor was capable of accepting one or two mannose residues, resulting in a major and a minor mannosylated product . Both products from each acceptor were isolated and their mass was confirmed by fast-atom bombardment-mass spectrometry (FABMS) . Characterization of each mannosylated product by exo-glycosidase digestion . acetolysis and linkage analysis by gas chromatography mass spectrometry of partially per-O-methylated alditols, revealed only alpha1-6-linked products . In addition . the antibiotic amphomycin selectively inhibited the formation of mannosylated products suggesting polyprenolmonophosphate-mannose (C15 50-P-Man) was the immediate mannose donor in all mannosylation reactions observed . The ability of synthetic disaccharides to act as acceptor substrates in this system, is most likely due to the action of a mycobacterial polyprenol-P-Man:mannan alpha1-6 mannosyltransferase involved in the biosynthesis of linear alpha1-6-linked lipomannan.

Rev Pneumol Clin, 2001 Apr, 57(2), 113 - 23
{Diagnosis and treatment of nosocomial pneumonia: bronchial fibroscopy, protected brushing and/or bronchial lavage is indispensable}; Chastre J; In case of suspected nosocomial lung infection in an intensive care patient, a strictly "clinical" strategy based on the physical exam and qualitative culture of tracheal secretions has three potential drawbacks: i) Numerous patients are given unnecessary antibiotic regimens unwarranted on the sole basis of colonization of the upper airways . In addition to the high cost of such regimens, these antibiotics also have important adverse effects favoring the emergence of multiresistant strains, and in addition, considerably complicating the search for the real cause and the treatment of the fever and the new lung images . ii) This strategy exposes the patient to diagnostic errors by omission if all patients with suspected infection are not treated . iii) Finally, even if the diagnosis of pneumonia is exact, the antibiotic prescribed on the basis of necessarily imprecise information can be most inappropriate or non-optimal in many cases . It is particularly difficult or often impossible to taper off the regimen on day 3 when tracheal cultures become available since the prescription would have to cover all the germs present in the upper airways even though only certain strains are undoubtedly causing the infection in the lung parenchyma . We prefer another strategy based on systematic bronchial fibroscopy before changing the antibiotic regimen in patients presenting signs suggestive of nosocomial pneumonia . The fibroscope allows us to obtain minimally-contaminated or non-contaminated specimens of the distal lung secretions in the suspected zone using the "Wimberley" brush for a protected sample and/or bronchoalveolar lavage . Although data in the literature on the usefulness of protected brushings and bronchoalveolar lavage specimens is rather confusing due to methodological differences, all the published work confirms that these techniques do allow identification of the germs present in the lung at the time of the sampling . Thus, on the basis of the culture results, it would be possible to discontinue any unnecessary antibiotic in patients with negative samples and inversely to use the narrowest possible treatment spectrum for those with positive samples, adapting the regimen to the susceptibility pattern or identified strains . The strongest arguments favoring this invasive strategy come from a multicentric French study on 413 patients with clinically suspected nosocomial pneumonia under artificial ventilation . The results demonstrated lower mortality in the fibroscopy group associated with a major reduction in the consumption of antibiotics.

Rev Pneumol Clin, 2001 Apr, 57(2), 79 - 89
{Prevention of nosocomial pneumonia in patients treated with invasive ventilation}; De Lassence A et al.; Nosocomial pneumonia is one of the primary causes of nosocomial infection in intensive care patients, leading to high mortality and prolonged hospitalization . Mechanical ventilation and its duration are major risk factors . When invasive ventilation is indispensable, preventive measures should aim at optimizing patient care by carefully applying basic rules of hygiene and recommended procedures for use of ventilation equipment . Different preventive measures have been proposed and should be considered in light of several criteria: the cost/benefit ratio, the level of proof (size of the study population, quality and pertinence of judgement criteria), feasibility, routine cost, and absence of secondary collateral adverse effects.

Antimicrob Agents Chemother, 2001 Jun, 45(6), 1682 - 7
Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of imipenem in healthy rats; Dupuis A et al.; A pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was developed to investigate the epileptogenic activity of imipenem in rats . Initially, animals received an intravenous infusion of imipenem at a rate of 2.65 mg min(-1) for 30 min . Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion . A dramatic delay was observed between concentrations of imipenem in serum and the EEG effect; this effect was accompanied by tremors and partial seizures . Indirect-effect models failed to describe these data, which were successfully fitted using an effect compartment model . The relationship between effect and concentration at the effect site was best described by a spline function . The elimination rate constant from the effect compartment was severalfold lower than that from the central compartment . The robustness of the model was then confirmed after administering the imipenem dose over 60 and 90 min . In conclusion, the successful PK-PD modeling of the imipenem EEG effect in rats constitutes a major improvement for better prediction of the epileptogenic risk associated with this antibiotic.

Minerva Chir, 2001 Apr, 56(2), 199 - 203
{Treatment of the ingrown toenail by phenol cauterization (ASLUF)}; Caronia V et al.; BACKGROUND: The aim of this study was to evaluate the clinical and the ethiopatogenetic aspects of the ingrown toenail, treated by usual surgical technique versus phenol wedge cauterization (ASLUF) . METHODS: From June 1990 to June 1999, 388 patients (218 male and 170 female patients, age range 9-90 years) were treated by 413 wedge ablation, surgical or chemical . After the operation, patients were controlled after 2 days, 1 week, 1 month, 6 months and 1 year . 109 patients were treated by usual surgical treatment, 260 patients by phenol cauterization (ASLUF), 19 by total ablation . RESULTS: 23 patients presented again ingrown toenail in the same place after few months, 20 patients after surgical treatment and 3 patients after phenol cauterization . All 23 patients were treated again without problems . CONCLUSIONS: In our personal opinion, the treatment of ingrown toenail is necessary soon, without the routine use of antibiotic therapy and the total ablation of the nail is not necessary . On this basis phenol wedge cauterization is the most suitable treatment for ingrown toenail with good cosmetic results, lower recurrence rate and from the functional point of view.

Biochemistry, 2001 May 22, 40(20), 5894 - 905
Solution structure of Co(III)-bleomycin-OOH bound to a phosphoglycolate lesion containing oligonucleotide: implications for bleomycin-induced double-strand DNA cleavage; Hoehn ST et al.; Bleomycin (BLM) is an antitumor antibiotic that is used clinically . Its major cause of cytotoxicity is thought to be related to BLM's ability to cause double-strand (ds) DNA cleavage . A single molecule of BLM appears to cleave both strands of DNA in the presence of its required cofactors Fe(2+) and oxygen without dissociating from the helix . A mechanism for this process has been proposed based on a model structure of the hydroperoxide of Co(III)-BLM (CoBLM) bound sequence-specifically to an intact duplex containing a GTAC site, a hot spot for ds cleavage {Vanderwall, D . E., Lui, S . M., Wu, W., Turner, C . J., Kozarich, J . W., and Stubbe, J . (1997) Chem . Biol . 4, 373-387} . In this paper, we present a structural model for the second cleavage event . Two-dimensional NMR spectroscopy and molecular modeling were carried out to study CoBLM bound to d(CCAAAGXACTGGG).d(CCCAGTACTTTGG), where X represents a 3'-phosphoglycolate lesion next to a 5'-phosphate . Assignments of 729 NOEs, including 51 between the drug and the DNA and 126 within the BLM molecule, have been made . These NOEs in addition to 96 dihedral angle constraints have been used to obtain a well-defined structural model for this complex . The model reveals that the bithiazole tail is partially intercalated between the T19 and the A20 of the duplex and that the metal binding domain is poised for abstraction of the T19 H4' in the minor groove . The modeling further reveals that the predominant conformation of the bithiazole protons is trans . Two cis conformations of these protons are also observed, and ROESY experiments provide evidence for interconversion of all of these forms . The relationship of these observations to the model for ds cleavage is presented.

J Clin Pharm Ther, 2001 Apr, 26(2), 93 - 101
Prescribing at the Primary Care Group level: census data and prescribing indicators; Lloyd DC et al.; OBJECTIVE: To examine the relationship between prescribing and morbidity, mortality and deprivation for the 481 Primary Care groups set up on 1 April 1999, by examining the prescribing of their constituent practices in the year 1998/99, i.e . the year before . DESIGN: Cross-sectional study . OUTCOME MEASURES: Set of 11 prescribing indicators taken from the Prescription Pricing Authority 'Toolkit' system; census measures of morbidity and deprivation and Standardized Mortality Ratio for those aged 75 and under . SETTING: All practices in England belonging to a Primary Care Group . RESULTS: Several of the indicators showed strong correlation with morbidity, mortality and, to a weaker extent, with deprivation . There was a negative correlation between the census-based measures and choice of more expensive alternatives or greater duration prescriptions for antibiotic prescribing and with the use of hormone replacement therapy (HRT) . Conversely, there was a positive correlation with use of premium products and drugs of limited therapeutic value . CONCLUSION: Practices in areas of greater need (as measured by permanent sickness and Standardized Mortality Ratio) seem to be trying to hold down costs by the way they prescribe antibiotics . Conversely, their use of premium price products pushes up their costs in the absence of clear evidence concerning compliance . The use of HRT is low in areas of high overall need.

J Clin Periodontol, 2001 May, 28(5), 446 - 52
The long-term effect of systemic tetracycline used as an adjunct to non-surgical treatment of advanced periodontitis; Ramberg P et al.; AIM: In the present study both the short- and the long-term effects were evaluated of a treatment that, during the phase of basic therapy, included administration of systemic tetracycline and non-surgical intervention . MATERIAL AND METHODS: 35 adult human subjects with advanced periodontitis, 19 females and 16 males, aged between 24 and 60 years, were included in a test group . 80 age- and sex-matched adult periodontitis subjects were recruited for a control group (42 females and 38 males) . A baseline examination included assessment of the following parameters: number of teeth, plaque, bleeding on probing, probing attachment level, probing pocket depth . In radiographs, the distance between the cemento-enamel junction and the alveolar bone crest was determined at all interproximal sites . The subjects were given oral hygiene instruction . The members of the test group were provided with tablets with 250 mg of tetracycline hydrochloride and were instructed to take 1 tablet 4x per day for a period of 3 weeks . No antibiotic was given to the subjects in the control group . During the 3-week interval, all participants received 4-6 sessions of non-surgical periodontal therapy . All subjects were subsequently enrolled in a maintenance care program and were provided with supportive periodontal therapy (SPT) 3-4x per year . Clinical re-examinations were performed after 1, 3, 5 and 13 years . RESULTS: The present investigation demonstrated that tetracycline administered during a 3-week period concomitant with non-surgical treatment enhanced the outcome of mechanical therapy . At the re-examination 1 year after active therapy, there was in the test group an average gain in probing attachment that was almost 3x higher than the gain that occurred in an age and sex matched Control group . Re-examinations after 3, 5, and 13 years of SPT disclosed that this short-term benefit was not maintained in the longer perspective . CONCLUSION: The beneficial effect of systemically administered tetracycline on probing attachment level occurred in the first year post-therapy . Annual rates of probing attachment level change from 1 to 13 years did not differ between groups.

Farmaco, 2001 Jan-Feb, 56(1-2), 113 - 6
Novel bone antiresorptive agents that selectively inhibit the osteoclast V-H+-ATPase; Farina C et al.; The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is a potential molecular target for the discovery of novel bone antiresorptive agents useful for the treatment of osteoporosis . In order to design novel compounds able to selectively inhibit the osteoclast V-ATPase we firstly identified the minimal structural requirements of bafilomycin A1, a macrolide antibiotic which potently inhibits all V-ATPases . This information allowed the design of 2-(indole)pentadienamide derivatives whose optimization led to a novel class of potent inhibitors that demonstrated a high degree of selectivity for the osteoclast V-ATPase . The most interesting derivative, SB-242784, was able to inhibit bone resorption by human osteoclasts in vitro and to completely prevent ovariectomy-induced bone loss in rats when administered orally at 10 mg kg(-1) day(-1) . Structure activity relationships of this class of compounds were investigated further by replacing the 2,4-pentadienoyl chain with suitable spacers able to maintain the correct orientation and distance between the indole ring and the amide moiety.

Biol Chem, 2001 Mar, 382(3), 479 - 81
Fluorescence correlation spectroscopy as a new method for the investigation of aptamer/target interactions; Schurer H et al.; Fluorescence correlation spectroscopy is an attractive tool for monitoring molecular interactions in solution . We report here a new and highly sensitive method for studying the interaction of aptamers with their targets using this technique . In vitro selection technology is a combinatorial method for the generation of nucleic acid receptors (aptamers) that are capable of binding to various target molecules . Using the in vitro selection approach we isolated RNAs which bind to the antibiotic moenomycin with high affinity . The formation of RNA-moenomycin complexes was studied by fluorescence correlation spectroscopy with a tetramethylrhodamine-labeled derivative of moenomycin.

Bull Soc Pathol Exot, 2001 Mar, 94(1), 5 - 7
{Clinical, endoscopic and histologic aspects of chronic Helicobacter pylori gastritis in Côte d'Ivoire: study of 102 patients}; Attia KA et al.; BACKGROUND: Helicobacter pylori (H . pylori) is the most frequent aetiological factor of chronic gastritis (CG) . The relationship between H . pylori gastritis, gastro-duodenal ulcer and some gastric cancers (adenocarcinoma, gastric MALT lymphoma) has now been proven . AIM: Describe clinical, endoscopical and histological aspects of H . pylori gastritis in Cote d'Ivoire . METHODS: Retrospective analysis of 1960 gastroscopy reports carry out between January 1994 and December 1995 . Analysis of clinical and gastric histological results in 137 patients . FINDINGS: Among 137 patients with gastric biopsy, 102 had H . pylori gastritis (68 men, 38 women, mean age: 39.3 years) and 35 had chemical gastritis . Epigastric pain was the most frequent symptom . The mucosa was frequently erythematous or exsudative at endoscopy . Histological anomalies were located in the antrum, the fundus or generalised, respectively in 33.3%, 25.5% and 41.2% of cases . Mild atrophic CG was more frequent in various locations . Gastritis activity was present in 81.4%, intestinal metaplasia in 18.6% and follicular lymphoid hyperplasia in 36.3% of cases . CONCLUSION: Clinical and endoscopical aspects of H . pylori gastritis did not present any particularities . Fundic gastritis without antral localisation was not unusual . This situation could be the result of antibiotic and gastric acid secretion inhibitor treatments.

Ann Pharmacother, 2001 May, 35(5), 636 - 40
Common prescriptions in ambulatory care in Lebanon; Hamadeh GN et al.; OBJECTIVE: To describe prescribing practices of family physicians in a staff model health maintenance organization at a university health center in Lebanon and estimate costs of such practices for common diseases . METHODS: All prescriptions issued between July 1, 1997, and June 30, 1998, were prospectively collected . The diagnoses made by physicians at each encounter were recorded, and the total price of medications prescribed was calculated . The core prescribing indicators as defined by the World Health Organization and the mean annual prescription price per person for the 25 most common diagnoses were calculated . RESULTS: Prescribing occurred in 27.1% of encounters, with a mean of 1.6 medications per encounter; 17.5% of all prescriptions included an antibiotic . Generic drugs and essential drugs each accounted for 2.9% of all medications . Approximately 50% of the consultations for either respiratory or ear infections resulted in a prescription . Cervical spine syndromes and lipid metabolism disorders cost most among recorded diagnoses, with mean annual prescription prices per person of US $2016 and $1128, respectively . CONCLUSIONS: The low rate of generic and essential drug prescribing, as well as the frequency of prescribing in respiratory infections, highlight the need for initiatives to help rationalize prescribing in primary care in Lebanon . Together with the diagnostic categories incurring high cost per person, these issues can be part of physician education or treatment guideline development . These measures may aid the government in its subsidy of primary health care centers.

Rev Stomatol Chir Maxillofac, 2001 Feb, 102(1), 26 - 33
{Infectious complications of mandibular osteotomy}; Cheynet F et al.; BACKGROUND: Infection is a rare complication after orthognathic surgery . A rate of 1% to 15% has been reported in the literature . We reviewed our experience . MATERIAL AND METHODS: We reviewed retrospectively 60 mandibular osteotomies performed between 1998 and 1999 . There were 41 women and 19 men, mean age 24 years . All were given antibiotic therapy using cefamandol 1500 mg preoperatively then 750 mg every 6 hours peroperatively and cefixime 400 mg/d postoperatively for 7 days . Patients were followed for at least 6 months after surgery . RESULTS: There were 10 infections (16% of the cases) involving a hematoma in 2 cases, adenitis in 1, osteitis on a cortical fragment in 2 and osteitis on implanted material in 5 . DISCUSSION: We defined infection following orthognathic surgery as a collection or purulent fistula with either a high polynuclear count in the discharge fluid or a positive culture . Both soft tissue (for example infection of a perimandibular hematoma) or bone infections were equally considered . We found two types of risk factors: patient-related or procedure-related . Patient-related factors included smoking, paradontal status, and dental hygiene . The main procedure-related factor was duration of surgery . Measures of prevention include extraction of the wisdom teeth, interruption of smoking, preoperative scaling and careful dental care, rigorous operative technique, antibiotic therapy.

Rev Clin Esp, 2001 Feb, 201(2), 65 - 8
{Community-acquired pneumonia requiring hospital admission . A comparison of the clinical management, resource use and prognosis by different medical specialties}; Medrano Gonzalez F et al.; OBJECTIVE: To evaluate whether there are differences regarding therapy, resource use and prognosis of inpatients due to community acquired pneumonia (CAP) in different clinical departments . METHODS: One-year retrospective study, using the discharge abstract, of all patients aged over 7 years admitted to the general hospital with the diagnosis of CAP . Comparison of the appropriateness of antibiotic therapy, mean hospital stay, use of invasive procedures, intrahospital mortality rate, and readmissions between the different clinical departments . RESULTS: A total of 511 patients were studied, 154 in Internal Medicine, 197 in Pneumology, 107 in Geriatrics and 53 in other departments, with moderate to severe underlying disease in 50.8%, severity criteria of CAP in 75%, and intrahospital mortality rate of 11.7% . No differences were observed regarding mean stay or appropriateness of antibiotic therapy . Invasive procedures were used most commonly in the Pneumology Department (12% vs 2%-7.5%; p = 0.001) . In the Geriatrics Department readmissions were most common (10% vs 1%-4%; p = 0.006) and intrahospital mortality rate (19% vs 8.6%-13.2%; p = 0.029) than in the remaining departments . Intrahospital mortality was associated with a moderate or severe underlying disease, neurologic disease, severity criteria of CAP and ICU admission, and readmissions with a moderate or severe underlying disease . CONCLUSIONS: There are relevant differences in intrahospital mortality rate and readmissions among patients with CAP in the different clinical departments, which seem to be associated with the underlying disease and the severity of the CAP.

J Bacteriol, 2001 Jun, 183(11), 3488 - 98
Functional analysis of relA and rshA, two relA/spoT homologues of Streptomyces coelicolor A3(2); Sun J et al.; Deletion of the (p)ppGpp synthetase gene, relA, of Streptomyces coelicolor A3(2) results in loss of production of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red) and delayed morphological differentiation when the mutant is grown under conditions of nitrogen limitation . To analyze the role of (p)ppGpp as an intracellular signaling molecule for the initiation of antibiotic production, several C-terminally deleted derivatives of S . coelicolor relA that could potentially function in the absence of ribosome activation were placed under the control of the thiostrepton-inducible tipA promoter . While 0.82- and 1.28-kb N-terminal segments failed to restore (p)ppGpp and antibiotic production upon induction in a relA null mutant, 1.46- and 2.07-kb segments did . Under conditions of phosphate limitation, deletion of relA had little or no effect on Act or Red synthesis, potentially reflecting an alternative mechanism for ppGpp synthesis . A second S . coelicolor RelA homologue (RshA, with 42% identity to S . coelicolor RelA) was identified in the genome sequence . However, deletion of rshA had no effect on the ability of the relA mutant to make Act and Red when grown under conditions of phosphate limitation . While high-level induction of tipAp::rshA in the relA mutant resulted in growth inhibition, low-level induction restored antibiotic production and sporulation . In neither case, nor in the relA mutant that was grown under phosphate limitation and producing Act and Red, could (p)ppGpp synthesis be detected . Thus, a ppGpp-independent mechanism exists to activate antibiotic production under conditions of phosphate limitation that can be mimicked by overexpression of rshA.

J Bacteriol, 2001 Jun, 183(11), 3468 - 75
Characterization and analysis of the PikD regulatory factor in the pikromycin biosynthetic pathway of Streptomyces venezuelae; Wilson DJ et al.; The Streptomyces venezuelae pikD gene from the pikromycin biosynthetic cluster was analyzed, and its deduced product (PikD) was found to have amino acid sequence homology with a small family of bacterial regulatory proteins . Database comparisons revealed two hypothetical domains, including an N-terminal triphosphate-binding domain and a C-terminal helix-turn-helix DNA-binding motif . Analysis of PikD was initiated by deletion of the corresponding gene (pikD) from the chromosome of S . venezuelae, resulting in complete loss of antibiotic production . Complementation by a plasmid carrying pikD restored macrolide biosynthesis, demonstrating that PikD is a positive regulator . Mutations were made in the predicted nucleotide triphosphate-binding domain, confirming the active-site amino acid residues of the Walker A and B motifs . Feeding of macrolide intermediates was carried out to gauge the points of operon control by PikD . Although the pikD mutant strain was unable to convert macrolactones (10-deoxymethynolide and narbonolide) to glycosylated products, macrolide intermediates (YC-17 and narbomycin) were hydroxylated with high efficiency . To study further the control of biosynthesis, presumed promoter regions from pik cluster loci were linked to the xylE reporter and placed in S . venezuelae wild-type and pikD mutant strains . This analysis demonstrated that PikD-mediated transcriptional regulation occurs at promoters controlling expression of pikRII, pikAI, and desI but not those controlling pikRI or pikC.

J Biol Chem, 2001 Jul 6, 276(27), 25088 - 95 Epub 2001 May 07.
A novel heat shock protein plays an important role in thermal stress management in cyanobacteria; Nakamoto H et al.; A novel heat shock gene, orf7.5, which encodes a putative acidic polypeptide of 63 amino acids, was cloned from the cyanobacterium Synechococcus sp . PCC 7942 . Northern blot analysis revealed the presence of 400- and 330-base orf7.5 mRNAs, which were barely detectable in the cells grown at 30 degrees C but increased transiently in response to heat shock at 40 or 45 degrees C . Primer extension analysis showed that the two mRNAs have different 5'-ends . Chloramphenicol enhanced the accumulation of the orf7.5 mRNA, whereas it inhibited the increase in the amount of the groESL mRNA . To reveal the role of the orf7.5 gene in thermal stress management, we constructed a stable mutant in which a gene conferring resistance to an antibiotic was inserted into the coding region of the orf7.5 gene . The interruption led to a marked inhibition of growth at 45 degrees C and a decrease in the basal and acquired thermo-tolerances at 50 degrees C in the transformants, indicating that the gene plays a role in thermal stress management . The orf7.5 mutant could be complemented with a return to the wild type phenotype by a DNA fragment containing orf7.5 but not by mutated orf7.5s, in which a nonsense mutation was generated by introducing a frameshift or a point mutation within the orf7.5-coding region . Thus, thermo-tolerance requires an appropriate translation product, not simply a transcript . Accumulation of the groESL transcript in the orf7.5 mutant was strongly reduced, suggesting that the orf7.5 gene product controls the expression of the groESL operon.

Dig Dis Sci, 2001 May, 46(5), 1077 - 82
Small intestine bacterial overgrowth and metabolic bone disease; Di Stefano M et al.; Small intestine bacterial overgrowth is a malabsorption syndrome and, therefore, it may contribute to the occurrence of metabolic bone disease . However, studies that evaluate the magnitude of this problem and the potential underlying mechanisms are still needed . Fourteen patients with bacterial overgrowth and 22 comparable healthy volunteers took part in this study . All patients were affected by conditions known to predispose to bacterial overgrowth . Diagnosis was based on the following criteria: increased breath hydrogen levels in the fasting state and/or increased breath hydrogen excretion after the ingestion of 50 g of glucose solution, improvement after a 10-day course of antibiotic therapy of severity of symptoms and of H2 excretion parameters . Measurement of bone mineral density by dual-energy x-ray absorptiometry at lumbar spine and femoral level and evaluation of nutritional status were performed . Physical activity, sunlight exposure, and cigarette smoking were also evaluated . Patients showed lumbar and femoral bone mineral density values significantly lower than control group; also the prevalence of bone loss at both lumbar and femoral levels was higher in patient group than in healthy volunteers . Body mass index was significantly lower in patients than in healthy volunteers . Lumbar and femoral bone mineral density were significantly correlated and both correlated with body mass index and with duration of symptoms . No correlation between BMD values and physical activity, sunlight exposure, and cigarette smoking was evident . Our results show that small intestine bacterial overgrowth is an important cofactor in the development of metabolic bone disease . The severity of bone loss is related to poor nutritional status and duration of malabsorption symptoms.

Pediatr Pulmonol, 2001 May, 31(5), 394 - 7
Bronchiolitis obliterans organizing pneumonia (BOOP) in a child with mild-to-moderate asthma: evidence of mast cell and eosinophil recruitment in lung specimens; Barbato A et al.; Bronchiolitis obliterans with organizing pneumonia (BOOP) is rarely described in children and little is known about its pathogenesis . This paper reports on an 11-year-old patient suffering from mild-to-moderate asthma . He presented with a retrocardiac density at chest computed tomography scan that was slow to resolve and failed to respond to antibiotic therapy . Open lung biopsy revealed a histological picture with buds of granulation tissue in respiratory bronchioles and alveolar ducts, with organized extensions into the alveoli . The use of monoclonal antibodies on biopsy specimens demonstrated the presence of an inflammatory process affecting not only the thickened alveolar walls, but also the remaining lung parenchyma, the pulmonary arteries, and the bronchioles . The inflammatory infiltrate consisted mainly of mast cells and eosinophils . The clinical condition improved with steroid therapy . To the best of the authors' knowledge, this is the first report of BOOP in an asthmatic child with recruitment of mast cells and eosinophils documented by using monoclonal antibodies .

Arch Soc Esp Oftalmol, 2001 Apr, 76(4), 249 - 58
{Comparative study between different conjunctival tissue adhesives}; Gomez Gonzalez JJ et al.; PURPOSE: To evaluate efficacy and clinical and histopathological tolerance of a new acrylic tissue adhesive (ADAL-2) compared to sutures (Vicryl) and other available tissue adhesives (Tisuacryl) for their use in conjunctival surgery . METHODS: This was an experimental study performed in New Zealand albino rabbits with conjunctival dissection and closure by ADAL-2 . Groups treated with Vicryl and Tisuacryl were compared regarding efficacy, clinical, and histological tolerance at 7, 28 and 42 days . RESULTS: Efficacy was similar in the three methods of conjunctival repositioning evaluated . Tolerance to ADAL-2 was similar to that of Vicryl suture and tolerance to ADAL-2 was superior to that to Tisuacryl . Histopathological results with ADAL-2 and Tisuacryl are similar . CONCLUSIONS: ADAL-2 tissue adhesive is an efficient and very well tolerated alternative for conjunctival closure in ophthalmic surgery.

Science, 2001 May 4, 292(5518), 897 - 902
Recognition of cognate transfer RNA by the 30S ribosomal subunit; Ogle JM et al.; Crystal structures of the 30S ribosomal subunit in complex with messenger RNA and cognate transfer RNA in the A site, both in the presence and absence of the antibiotic paromomycin, have been solved at between 3.1 and 3.3 angstroms resolution . Cognate transfer RNA (tRNA) binding induces global domain movements of the 30S subunit and changes in the conformation of the universally conserved and essential bases A1492, A1493, and G530 of 16S RNA . These bases interact intimately with the minor groove of the first two base pairs between the codon and anticodon, thus sensing Watson-Crick base-pairing geometry and discriminating against near-cognate tRNA . The third, or "wobble," position of the codon is free to accommodate certain noncanonical base pairs . By partially inducing these structural changes, paromomycin facilitates binding of near-cognate tRNAs.

Exp Cell Res, 2001 May 15, 266(1), 53 - 63
5-Bromodeoxyuridine suppresses position effect variegation of transgenes in HeLa cells; Suzuki T et al.; An ectopic gene integrated in the host genome is occasionally silenced due to a position effect of its adjacent chromatin structure . We found that 5-bromodeoxyuridine clearly activated such a transgene in HeLa cells . The transgene was also activated to various degrees by inhibitors of histone deacetylase, DNA topoisomerases, or DNA methyltransferase . The peptide antibiotic distamycin A potentiated markedly the effect of 5-bromodeoxyuridine . Transient expression of an artificial AT-hook protein termed MATH20 also potentiated its effect although significantly activated the transgene alone . Since distamycin A and MATH20 are able to displace histone H1 and other DNA-binding proteins bound to specific AT-rich sequences by a dominant, mutually exclusive fashion, these results suggest that 5-bromodeoxyuridine targets such an AT-rich sequence located adjacent to the silenced transgene, resulting in chromatin accessibility .

Arch Pharm Res, 2001 Apr, 24(2), 100 - 4
Electrochemical behavior and differential pulse polarographic determination of rifampicin in the pharmaceutical preparations; Hahn Y et al.; Differential pulse polarographic (DPP) analytical procedure for the rifampicin antibiotic, which can be applied to monitor its synthetic process from the starting antibiotic of rifamycin B or rifamycin SV, has been developed based on the electrochemical reduction of an azomethine group . Rifampicin exhibited a cathodic peak due to the azomethine group in the side chain of 3-{(4-methyl-1-piperazinyl)imino}methyl moiety and another cathodic peak due to the carbonyl group in rifamycin SV by DPP The experimental peak potential shift of an azomethine reduction was -73 mV/pH in the pH range between 3.0 and 7.5, agreeing with involvement of 4 e- and 5 H+ in its reduction . By the cyclic voltammetric(CV) studies, the azomethine and the carbonyl reductions in rifampicin were processed irreversibly on the mercury electrode . The plot of peak currents vs . concentrations of rifampicin ranging 1.0 x 10(-7) M tp approximately 1.0 x 10(-5) M yielded a straight line with a correlation coefficient of 0.9996 . The detection limit was 1.0 x 10(-8) M with a modulation amplitude of 50 mV . DPP has been successfully applied for the determination of rifampicin in the pharmaceutical preparations.

Infection, 2001 Mar-Apr, 29(2), 71 - 4
Concentration of soluble CD4, CD8 and CD25 receptors in early localized and early disseminated Lyme borreliosis; Zajkowska J et al.; BACKGROUND: The aim of this study was to evaluate the concentrations of soluble CD4, CD8 and CD25 antigens in the serum of patients with early LocaLized, (group I, n = 22 patients) and early disseminated Lyme borreliosis (group II n = 23 patients), before and after antibiotic therapy compared with controls (group III n = 7 healthy persons) . MATERIALS AND METHODS: The diagnosis of Lyme borreliosis based on clinical features was confirmed by ELISA and Western blot . The assays of sCD4, sCD8 and sCD25 concentrations were performed using Endogen (USA) kits . RESULTS: In group I the sCD4 level decreased in examination 2 (p < 0.001) compared to examination 1 . The mean concentration of sCD8 in initial examination 1 in group II was higher than in controls (p < 0.0001); it decreased in examination 2 but was still higher (p < 0.01) than in controls (p < 0.006) . Prior to treatment mean sCD25 concentration in group II was higher compared to controls (p < 0.0008) like in examination 2 after treatment (p < 0.02) and this persisted . The mean value of sCD8 in initial examination 1 before treatment in group II was higher than in group I (p < 0.00001) . CONCLUSION: Increased initial concentrations of sCD8 and sCD25 indicate the activation of CD8 and CD25 lymphocytes and their role in immunopathogenesis of Lyme disease . Elevated levels of sCD8 in group II before and after treatment suggest a significant involvement of CD8 lymphocytes, indicating the role of long-lasting cellular response in this stage of Lyme disease.

J Med Microbiol, 2001 May, 50(5), 430 - 5
Inhibition of Helicobacter pylori infection by bovine milk glycoconjugates in a BAlb/cA mouse model; Wang X et al.; The attachment of Helicobacter pylori to the human gastric mucosa is a complex process involving several specific structures recognised by the cell surface receptors . Sialylated multivalent high mol . wt glycoproteins have been shown to inhibit H . pylori sialic acid-specific haemagglutination . This study explored whether sialylated glycoconjugates from bovine milk could inhibit an experimental H . pylori infection in a mouse model . BALB/cA mice (6-8 weeks old) were inoculated with a mouse-passaged H . pylori strain 317p . Four weeks after infection the mice were given lactoferrin (iron-free LF or 20% iron-saturated LF) or bovine milk fat globule membrane fractions (MFGM or defatted MFGM) orally (400 mg/kg body weight) once daily for 10 days and then killed to examine for bacterial colonisation and gastritis . Mice treated with iron-free LF, 20% iron-saturated LF, MFGM or defatted MFGM showed 30%, 10%, 20% or 20% healing rates, respectively, when compared with the H . pylori-infected control . Gastric colonisation by H . pylori was remarkably decreased in all mice treated with bovine milk glycoconjugates and the inflammation score was also significantly lower in treated mice than in infected control animals . The fact that there was no significant difference between iron-free LF and iron-saturated LF or MFGM and defatted MFGM suggested that iron is not crucial for inhibition of H . pylori by lactoferrin and that the lipid part of MFGM is not important for anti-H . pylori activity . In conclusion, bovine milk glycoconjugates showed potencies to inhibit H . pylori infection in this mouse model and, therefore, could be considered as candidates for non-antibiotic strategies against H . pylori infection in man.

Pharmacoepidemiol Drug Saf, 2000 Dec, 9(7), 549 - 56
Postmarketing surveillance of medications and pregnancy outcomes: clarithromycin and birth malformations; Drinkard CR et al.; PURPOSE: This retrospective surveillance study used linked administrative claims data and medical records to determine the rate and types of birth malformations in infants born to women exposed to the antibiotic, clarithromycin (Biaxin), during the first trimester of pregnancy . METHODS: Pharmacy and hospital claims from eight geographically diverse health plans were used to identify women who had a delivery claim within 270 days of a clarithromycin prescription over a 5-year period (1991-1995) . Hospital delivery admission medical records for 143 mothers and their 149 infants were abstracted to identify birth malformations . RESULTS: Five infants were identified with major malformations, three with minor malformations, and four with undescended testicles likely to resolve with time . The observed rate of 3.4% (95% CI, 0.5, 6.3) for major malformations was not statistically significantly different compared to an expected rate of 2.8% based on earlier national data . There was no consistency across types of major malformations . CONCLUSIONS: These results provide no evidence that clarithromycin is a likely major teratogen in humans . Use of claims data is one way to evaluate quickly and efficiently the safety of prescription medications in humans during pregnancy, especially when both exposure and outcome are rare.

Ear Nose Throat J, 2001 Apr, 80(4), 217 - 8, 222-3
Bilateral submandibular gland infection presenting as Ludwig's angina: first report of a case; Honrado CP et al.; We diagnosed and treated a case of Ludwig's angina in a 45-year-old man who had edema of the floor of mouth and the tongue along with bilateral submandibular sialadenitis and sialolithiasis . We secured the patient's airway via nasal fiberoptic intubation in the surgical intensive care unit and administered intravenous antibiotics . The edema subsided, and the patient was extubated on the third postoperative day and discharged shortly thereafter . To our knowledge, this is the first reported case of a patient with bilateral submandibular sialadenitis and sialolithiasis presenting as Ludwig's angina . Despite the decreasing incidence of this disease, Ludwig's angina remains an important disease process because a failure to control the airway can have disastrous consequences . Proper diagnosis, airway control, antibiotic therapy, and occasionally surgical management are essential to ensure the safety of the patient.

Ann Clin Lab Sci, 2001 Apr, 31(2), 171 - 8
Search for immunomodulatory effects of blood transfusion in gastric cancer patients: flow cytometry of Th1/Th2 cells in peripheral blood; Sun CF et al.; Allogeneic transfusion seems to drive the immune system toward a Th2 response and away from a Th1 response, providing a hypothetical mechanism for transfusion-induced immunomodulation . By means of an intracytoplasmic cytokine detection technique with flow cytometry, it is possible to measure Th1 and Th2 cells derived from peripheral blood mononuclear cells . This study evaluated the presence of transfusion-induced immunomodulation in 11 gastric cancer patients after gastrectomy with perioperative blood transfusion, compared to 11 gastric cancer patients who were treated by gastrectomy without transfusion . Lymphocytes subsets, including CD4 T cells, CD8 T cells, CD4/CD8 Ratio, CD2(+) T cells, CD3(+) T cells, and CD19(+) B cells, were measured in these patients, as well as variables that might suggest transfusion-induced immunomodulation, such as duration of antibiotic use, duration of hospital stay, and total hospital charges . This study also measured changes in the Th1/Th2 ratio . Th1 and Th2 lymphocytes were characterized by measuring intracellular expression of cytokines with flow cytometry . Cells were stimulated with phorbol myristate acetate and ionomycin in the presence of brefeldin-A . The results showed no significant differences in lymphocyte subsets, Th1/Th2 ratio, total hospital charges, or duration of antibiotic utilization between the groups of transfused and non-transfused gastric cancer patients after gastrectomy . The only significant difference was a longer hospital stay for transfused patients (mean 20.5 da) compared to non-transfused patients (mean 16.2 da) . The anticipated finding of a Th2 response after blood transfusion was not observed . A larger group of patients may be needed to document such an effect, since many confounding variables affect the morbidity and outcome of surgery in these patients.

Biochim Biophys Acta, 2001 Apr 23, 1538(2-3), 234 - 41
Daunorubicin attenuates tumor necrosis factor-alpha-induced biosynthesis of plasminogen activator inhibitor-1 in human umbilical vein endothelial cells; Soeda S et al.; The anthracycline antibiotic daunorubicin is reported to induce apoptosis in cells by triggering ceramide generation through de novo synthesis or sphingomyelin hydrolysis . Treatment of human umbilical vein endothelial cells (HUVEC) with daunorubicin markedly decreased the mRNA expression and protein release of plasminogen activator inhibitor-1 (PAI-1) . This cellular event was accompanied by a significant increase in the total ceramide content in HUVEC . On the other hand, tumor necrosis factor (TNF)-alpha treatment of HUVEC led to an increase in both PAI-1 mRNA expression and protein release, and an enhancement of total ceramide content was also observed . The stimulating effect of TNF-alpha on PAI-1 synthesis was attenuated by the pretreatment of HUVEC with daunorubicin . Interestingly, the daunorubicin-induced increase in ceramide content was blocked by addition of the potent ceramide synthase inhibitor fumonisin B(1), while the TNF-alpha-induced ceramide increase was not affected by this drug . Fumonisin B(1) treatment restored the daunorubicin-induced decrease in PAI-1 release to approximately 70% of the control, but did not affect the TNF-alpha-induced increase in PAI-1 release . Thus, these data imply the possibility that the subcellular topology of ceramide production determines its lipid mediator function in the regulation of PAI-1 synthesis in HUVEC, because both TNF-alpha and daunorubicin could increase the ceramide levels.

Biochem J, 2001 May 15, 356(Pt 1), 287 - 96
Phosphatidylinositol transfer proteins and protein kinase C make separate but non-interacting contributions to the phosphorylation state necessary for secretory competence in rat mast cells; Pinxteren JA et al.; Mast cells permeabilized by streptolysin O undergo exocytosis when stimulated with Ca(2+) and guanosine 5'-{gamma-thio}triphosphate but become progressively refractory to this stimulus if it is delayed . This run-down of responsiveness occurs over a period of 20-30 min, during which the cells leak soluble and tethered proteins . We show here that withdrawal of ATP during the process of run-down is strongly inhibitory but that as little as 25 microM ATP can extend responsiveness significantly; this effect is maximal at 50 microM . When phosphatidylinositol transfer proteins (PITPs) are provided to cells at the time of permeabilization, run-down is retarded . We conclude that in the presence of ATP they convey substrates for phosphorylation that are essential for exocytosis and thus interact with the regulatory machinery . Furthermore, we show that PITPalpha and PITPbeta have additive effects in this mechanism, suggesting that they are not functionally redundant . Alternatively, secretion from run-down cells can be inhibited by the aminoglycoside antibiotic neomycin, which is understood to bind to phosphoinositide headgroups, and by a PH (pleckstrin homology) domain polypeptide that binds phosphoinositides . The apparent displacement of neomycin by exogenous PITPs suggests that these proteins screen essential lipids . Secretion from run-down cells is also inhibited by 1-O-hexadecyl-2-O-methyl-rac-glycerol (AMG-C(16)), an inhibitor of protein kinase C . The lack of synergy between neomycin and AMG-C(16) suggests that protein kinase C independently provides a second essential component through protein phosphorylation and that there are two independent phosphorylation pathways necessary for secretion competence.

Br J Cancer, 2001 May 4, 84(9), 1272 - 9
The ratio of single- to double-strand DNA breaks and their absolute values determine cell death pathway; Tounekti O et al.; Bleomycin is a cytotoxic antibiotic that generates DNA double-strand breaks (DSB) and DNA single-strand breaks (SSB) . It is possible to introduce known quantities of bleomycin molecules into cells . Low amounts kill the cells by a slow process termed mitotic cell death, while high amounts produce a fast process that has been termed pseudoapoptosis . We previously showed that these types of cell death are a direct consequence of the DSB generated by bleomycin . Here, we use deglyco-bleomycin, a bleomycin derivative lacking the carbohydrate moiety . Although this molecule performs the same nucleophilic attacks on DNA as bleomycin, we show that deglyco-bleomycin is at least 100 times less toxic to Chinese hamster fibroblasts than bleomycin . In fact, deglyco-bleomycin treatment results in apoptosis induction . In contrast, however, deglyco-bleomycin was found to generate almost exclusively SSB . Our results suggest that more than 150 000 SSB per cell are required to trigger apoptosis in Chinese hamster fibroblasts and that SSB are 300 times less toxic than DSB . Taken together with previous studies on bleomycin, our data demonstrates that cells can die by apoptosis, mitotic cell death, or pseudoapoptosis, depending on the number of DNA breaks and on the ratio of SSB to DSB .

Biomaterials, 2001 Jun, 22(11), 1393 - 400
Adsorption and release studies of sodium ampicillin from hydroxyapatite and glass-reinforced hydroxyapatite composites; Queiroz AC et al.; As a potential therapy for periodontitis, sodium ampicillin, a broad spectrum antibiotic, was adsorbed onto hydroxyapatite (HA) and glass-reinforced hydroxyaptite (GR-HA) composites, and was subsequently released in vitro . The sodium ampicillin, was adsorbed more on HA compared to the GR-HA composites . X-ray diffraction (XRD) and Rietveld analysis were used to identify and quantify the levels of HA and beta-tricalcium phosphate (beta-TCP) in the microstructure of the GR-HA composites . Lattice parameters changes were observed for the beta-TCP phase dependant on the amount of glass added . The release kinetics were shown to be divided into three stages, the first of which where a large amount of sodium ampicillin is released, followed by a slower release rate and then a final stage where the release amount approaches zero, until no more sodium ampicillin was present . X-ray photoeletron spectroscopy (XPS) studies were carried out in order to ensure that the entire antibiotic adsorbed onto the materials had been released . These kinetics studies have indicated the possibility of using these materials as possible carriers for drug delivery.

Fertil Steril, 2001 May, 75(5), 1017 - 9
Hydrosalpinx treated with extended doxycycline does not compromise the success of in vitro fertilization; Hurst BS et al.; OBJECTIVE: To determine if extended treatment with doxycycline before and after an in vitro fertilization (IVF) procedure can minimize the detrimental effect of a hydrosalpinx . DESIGN: Retrospective analysis . SETTING: University IVF program . PATIENT(S): Patients undergoing IVF, including 17 with a hydrosalpinx, 25 with adhesions or proximal tubal occlusion, and 22 with endometriosis or unexplained infertility . INTERVENTION(S): Women with a documented hydrosalpinx were prescribed doxycycline 100 mg twice daily starting 1 week before expected retrieval and continued until 6 days after retrieval . No antibiotics were prescribed in the other groups . MAIN OUTCOME MEASURE(S): Implantation rates and IVF outcomes . RESULT(S): Implantation rates were 30% for the doxycycline-treated group of patients with a hydrosalpinx, 27% for the group with tubal occlusion/adhesion, and 24% for the group with endometriosis or unexplained infertility . Eight (47%) of 17 patients with a hydrosalpinx had a live birth, compared with 11 (44%) of 25 for the group with tubal occlusion/adhesion and 12 (55%) of 22 for the group with endometriosis/unexplained infertility . There were no differences between the groups in patient age, number of oocytes retrieved, fertilization rate, or number of blastomeres of the transferred embryos . CONCLUSION(S): No detrimental effect of a hydrosalpinx was evident for patients treated with extended doxycycline . Tremendous cost savings can be realized if treatment with 2 weeks of an inexpensive antibiotic provides outcomes comparable to surgical correction of a hydrosalpinx before IVF.

Enferm Infecc Microbiol Clin, 2001 Mar, 19(3), 93 - 8
{Plasmatic concentrations of fibronectin as marker of clinical course among septic patients}; Ruiz G et al.; INTRODUCTION: It is difficult to follow up the patients with sepsis because of the underlying pathology or the presence of complications . The attending physician needs to know as soon as possible the response to the antibiotic therapy . Is therefore necessary to find real time biological markers that will help to understand the clinical situation of the infected patient.It has been demonstrated that fibronectin (Fn) is an early marker of sepsis, so it seemed plausible its use in the clinical monitoring of the septic patient . MATERIAL: We have used plasmatic concentrations of Fn in the follow up of sepic patients admitted to the Hospital de Segovia from February to August, 1995 . There were two control groups: one of healthy volunteers and another of varied pathology . RESULTS: We have applied the multiple comparison rule of Bonferroni to demonstrate that plasma Fn is a negative acute phase reactant, with almost undetectable levels while the patient is in critical condition . An effective treatment prompts plasma Fn to rise significantly within two days . DISCUSSION: Plasma Fn concentration by itself or in an score system could help in the follow up of the septic patients.

Cell Transplant, 2001 Mar-Apr, 10(2), 209 - 21
In vitro and in vivo tetracycline-controlled myogenic conversion of NIH-3T3 cells: evidence of programmed cell death after muscle cell transplantation; Del Bo R et al.; Ex vivo gene therapy of Duchenne muscular dystrophy based on autologous transplantation of genetically modified myoblasts is limited by their premature senescence . MyoD-converted fibroblasts represent an alternative source of myogenic cells . In this study the forced MyoD-dependent conversion of murine NIH-3T3 fibroblasts into myoblasts under the control of an inducible promoter silent in the presence of tetracycline was evaluated . After tetracycline withdrawal this promoter drives the transcription of MyoD in the engineered fibroblasts, inducing their myogenesis and giving rise to beta-galactosidase-positive cells . MyoD-expressing fibroblasts withdrew from the cell cycle, but were unable to fuse in vitro into multinucleated myotubes . Five days following implantation of engineered fibroblasts in muscles of C57BL/10J mice we observed a sevenfold increase of beta-galactosidase-positive regenerating myofibers in animals not treated with antibiotic compared with treated animals . After 1 week the number of positive fibers decreased and several apoptotic myonuclei were detected . Three weeks following implantation of MyoD-converted fibroblasts in recipient mice, no positive "blue" fiber was observed . Our results suggest that transactivation by tetracycline of MyoD may drive an in vivo myogenic conversion of NIH-3T3 fibroblasts and that, in this experimental setting, apoptosis plays a relevant role in limiting the efficacy of engineered fibroblast transplantation . This work opens the question whether apoptotic phenomena also play a general role as limiting factors of cell-mediated gene therapy of inherited muscle disorders.

Am J Med, 2001 Apr 15, 110(6), 451 - 7
Decreased mortality after implementation of a treatment guideline for community-acquired pneumonia; Dean NC et al.; PURPOSE: We developed a pneumonia guideline at Intermountain Health Care that included admission decision support and recommendations for antibiotic timing and selection, based on the 1993 American Thoracic Society guideline . We hypothesized that guideline implementation would decrease mortality . SUBJECTS AND METHODS: We included all immunocompetent patients > 65 years with community-acquired pneumonia from 1993 through 1997 in Utah; nursing home patients were excluded . We compared 30-day mortality rates among patients before and after the guideline was implemented, as well as among patients treated by physicians who did not participate in the guideline program . RESULTS: We observed 28,661 cases of pneumonia, including 7,719 (27%) that resulted in hospital admission . Thirty-day mortality was 13.4% (1,037 of 7,719) among admitted patients and 6.3% (1,801 of 28,661) overall . Mortality rates (both overall and among admitted patients) were similar among patients of physicians affiliated and not affiliated with Intermountain Health Care before the guideline was implemented . For episodes that resulted in hospital admission after guideline implementation, 30-day mortality was 11.0% among patients treated by Intermountain Health Care-affiliated physicians compared with 14.2% for other Utah physicians . Analysis that adjusted by logistic regression for age, sex, rural versus urban residences, and year confirmed that 30-day mortality was lower among admitted patients who were treated by Intermountain Health Care-affiliated physicians (odds ratio {OR}: 0.69; 95% confidence interval {CI}: 0.49 to 0.97; P = 0.04) and was somewhat lower among all pneumonia patients (OR: 0.81; 95% CI: 0.63 to 1.03; P = 0.08) . CONCLUSION: Implementation of a pneumonia practice guideline in the Intermountain Health Care system was associated with a reduction in 30-day mortality among elderly patients with pneumonia.

J Chromatogr A, 2001 Apr 6, 912(2), 369 - 73
Isolation and structural characterization of polymyxin B components; Orwa JA et al.; Polymyxin B is a peptide antibiotic complex present as sulphate . The components were separated preparatively on a poly(styrene-divinylbenzene) (PLRP-S), 1000 A, 8 microm, 250 x 12.5 mm I.D . stationary phase maintained at 60 degrees C and using 215 nm detection . Elution was carried out with acetonitrile-sodium sulphate solution (0.7%, m/v; pH adjusted to 2.5 with trifluoroacetic acid)-water (18:50:32, v/v) at a flow-rate of 4.0 ml/min . Seven polymyxin B components were isolated and characterized using 1H and 13C NMR . The molecular masses were confirmed by mass spectrometry . The structures of two components were determined for the first time . Polymyxins B5 and B6 were identified as having the same composition as polymyxin B1 except that the fatty acid moiety was nonanoic acid and 3-hydroxy-6-methyloctanoic acid, respectively.

Nurse Pract, 2001 Apr, 26(4), 36 - 8, 41-2, 45; quiz 45-7
Managing dog, cat, and human bite wounds; Bower MG; Many bite wound patients seek treatment in primary care clinics instead of emergency departments . Without treatment, bite wounds can become infected . Presenting symptoms are usually wound site pain with cellulitis and purulent drainage . The infection originates from the oropharyngeal flora of the biting animal or human and the victim's skin . Primary care clinicians must be able to assess and manage animal and human bites, initiate antibiotic therapy if indicated, and refer patients for surgery or rabies prophylaxis when appropriate . Prompt assessment and treatment can prevent most bite wound complications.

Hinyokika Kiyo, 2001 Mar, 47(3), 203 - 6
{Seminal vesicle cyst with ipsilateral renal agenesis: a case report}; Kajita Y et al.; A 26-year-old man was referred to our hospital for further evaluation of a cystic lesion in the pelvis . He was completely asymptomatic, although he experienced gross hematuria 10 months before his visit . Drip infusion pyelography (DIP) and abdominal computerized tomography (CT) showed a cystic structure behind the bladder and absence of the left kidney . Transrectal ultrasonography (TRUS) suggested left ejaculatory duct obstruction and seminal vesicle deformity . On cystoscopy a large bulging mass under the left side of the bladder was seen . The left half of the trigone and left ureteral orifice were absent . Vasovesiculography demonstrated dilated and tortuous left seminal vesicle . Three days after this procedure, the patient suffered left epididymitis . It did not respond rapidly to antibiotic therapy, so percutaneous drainage of the cyst was performed . He has been completely free of symptoms and no seminal vesicle cysts have been detected on TRUS at five months follow-up.

Handchir Mikrochir Plast Chir, 2001 Mar, 33(2), 101 - 7
{Treatment of chronic osteomyelitis of the tarsal bones with free muscle flaps}; Kuzbari R et al.; Although the value of free muscle flaps in the treatment of chronic osteomyelitis of the lower leg is well documented, only few reports deal with the use of free muscle flaps for treatment of osteomyelitis of the tarsal bones . Four patients with chronic osteomyelitis of the tarsal bones (in three patients several bones were involved) were treated using the following regimen: radical debridement, coverage with a free muscle flap, and systemic antibiotic therapy . In two patients, infection recurred following primary transplantation of the muscle flap . In one of these patients, recurrence was controlled by repeating the same regimen . In the other patient, debridement was repeated and the calcaneus was transposed to obliterate the resultant bone cavity . At follow-up (mean 19 months following last surgical procedure), all four patients showed no evidence of infection and were fully weight-bearing . Chronic osteomyelitis of tarsal bones can be successfully treated by radical debridement and coverage with muscle flaps, even in advanced stages of the disease . The clinical and anatomical peculiarities of this region, however, have to be taken into consideration.

Bull Exp Biol Med, 2001 Jan, 131(1), 94 - 8
Detection of rifampicin-resistant Mycobacterium tuberculosis strains by hybridization and polymerase chain reaction on a specialized TB-microchip; Mikhailovich VM et al.; Two alternative methods for identification of rifampicin-resistant strains of Mycobacterium tuberculosis on biological microchips are developed . The methods are based on detection of point mutations and other rearrangements in the rpoB gene region determining rifampicin resistance . Hybridization on TB-microchip detects 30 mutant variants of DNA in rifampicin-resistant strains (about 95% of all resistant forms) . Allele-specific microchip PCR shortens the duration of analysis to 1.5 h . These methods can be used in clinical diagnostic laboratories for evaluating drug resistance/sensitivity of tuberculosis agent and for monitoring of the efficiency of antibiotic therapy.

J Antimicrob Chemother, 2001 May, 47(5), 711 - 3
Pancreatic concentrations of cefepime; Delcenserie R et al.; The concentrations of cefepime in pancreatic pseudocyst fluid (n = 4), pancreatic tissue (n = 4) and pancreatic fistula fluid (n = 1), and simultaneous plasma concentrations, were measured after intravenous administration of a single 2 g dose to nine patients . Mean plasma concentration was 27.4 mg/L between 120 and 200 min after the end of infusion . Mean pancreatic cefepime concentration was 6.3 mg/L in pseudocyst and 10.7 mg/L in pancreatic tissue . Cefepime was detected by 30 min after the end of the perfusion in pancreatic fistulae fluid, and persisted at 8 h . We conclude that cefepime is a potentially useful antibiotic in prevention and treatment of pancreatic infection.

Aliment Pharmacol Ther, 2001 May, 15(5), 613 - 24
A systematic comparison of triple therapies for treatment of Helicobacter pylori infection with proton pump inhibitor/ ranitidine bismuth citrate plus clarithromycin and either amoxicillin or a nitroimidazole; Janssen MJ et al.; BACKGROUND: Triple therapies with proton pump inhibitor/ranitidine bismuth citrate (RBC), clarithromycin (C) and either amoxicillin (A) or a nitroimidazole (I) are widely accepted as treatment for Helicobacter pylori infection . However, it is not clear which of these antibiotic combinations should be preferred . AIM: To evaluate whether there is a difference in efficacy between triple therapies with proton pump inhibitor/RBC, clarithromycin and either amoxicillin or a nitroimidazole . METHODS: The literature was examined for randomized trials comparing proton pump inhibitor/RBC-C-A and proton pump inhibitor/RBC-C-I . Studies were grouped according to the type of acid inhibitor used (proton pump inhibitor or RBC) and differences between pooled cure rates were calculated . RESULTS: Forty-seven studies were identified: seven using RBC, 39 using proton pump inhibitor, one using both . RBC-C-I was somewhat superior to RBC-C-A, although this difference only reached statistical significance in intention-to-treat analysis . Overall, proton pump inhibitor-C-I and proton pump inhibitor-C-A were equally effective, but in nitroimidazole-susceptible strains, proton pump inhibitor-C-I performed better, in nitroimidazole-resistant strains, proton pump inhibitor-C-A performed better . No serious side-effects were reported and pooled drop-out rates were equal . CONCLUSIONS: In general, proton pump inhibitor-C-I and proton pump inhibitor-C-A are equally effective and therefore other factors such as local prevalence of resistant strains, cost of therapy and options for second-line treatment should determine which regimen should be preferred . When using RBC, the RBC-C-I combination is somewhat superior to RBC-C-A.

Acta Orthop Scand, 2001 Feb, 72(1), 83 - 5
High-pressure saline washing of allografts reduces bacterial contamination; Hirn MY et al.; 60 fresh-frozen bone allografts were contaminated on the operating room floor . No bacterial growth was detected in 5 of them after contamination . The remaining 55 grafts had positive bacterial cultures and were processed with three methods: soaking in saline, soaking in antibiotic solution or washing by high-pressure saline . After high-pressure lavage, the cultures were negative in three fourths of the contaminated allografts . The corresponding figures after soaking grafts in saline and antibiotic solution were one tenth and two tenths, respectively . High-pressure saline cleansing of allografts can be recommended because it improves safety by reducing the superficial bacterial bioburden.

Am J Emerg Med, 2001 May, 19(3), 211 - 3
Emphysematous cystitis: a radiographic diagnosis; O'Connor LA et al.; Emphysematous cystitis is a somewhat uncommon entity in which early diagnosis and treatment play a key role in avoiding potentially high morbidity and mortality . An elderly woman with emphysematous cystitis and no comorbid factors, except advanced age, is presented . This case illustrates the key features in the radiographic diagnosis of this unusual disease . Discussion of the cause, diagnosis, and treatment of emphysematous cystitis emphasizes prompt recognition, drainage of the bladder and use of appropriate broad spectrum antibiotic therapy.

J Bacteriol, 2001 May, 183(10), 3193 - 203
Roles of aconitase in growth, metabolism, and morphological differentiation of Streptomyces coelicolor; Viollier PH et al.; The studies of aconitase presented here, along with those of citrate synthase (P . H . Viollier, W . Minas, G . E . Dale, M . Folcher, and C . J . Thompson, J . Bacteriol . 183:3184-3192, 2001), were undertaken to investigate the role of the tricarboxylic acid (TCA) cycle in Streptomyces coelicolor development . A single aconitase activity (AcoA) was detected in protein extracts of cultures during column purification . The deduced amino acid sequence of the cloned acoA gene constituted the N-terminal sequence of semipurified AcoA and was homologous to bacterial A-type aconitases and bifunctional eukaryotic aconitases (iron regulatory proteins) . The fact that an acoA disruption mutant (BZ4) did not grow on minimal glucose media in the absence of glutamate confirmed that this gene encoded the primary vegetative aconitase catalyzing flux through the TCA cycle . On glucose-based complete medium, BZ4 had defects in growth, antibiotic biosynthesis, and aerial hypha formation, partially due to medium acidification and accumulation of citrate . The inhibitory effects of acids and citrate on BZ4 were partly suppressed by buffer or by introducing a citrate synthase mutation . However, the fact that growth of an acoA citA mutant remained impaired, even on a nonacidogenic carbon source, suggested alternative functions of AcoA . Immunoblots revealed that AcoA was present primarily during substrate mycelial growth on solid medium . Transcription of acoA was limited to the early growth phase in liquid cultures from a start site mapped in vitro and in vivo.

J AOAC Int, 2001 Mar-Apr, 84(2), 350 - 3
Survey of residual tetracyclines in kidneys of diseased animals in Aichi Prefecture, Japan (1985-1997); Oka H et al.; A survey was conducted to determine the incidence of tetracycline antibiotic (TCAs) residues in the kidneys of slaughtered animals that did not pass inspection for human consumption by the Japanese Food Sanitation Law and the Meat Inspection Law at the slaughterhouses in Aichi Prefecture, Japan, from April 1985 to March 1998 . The kidneys were analyzed by the AOAC Official Method 995.09 . Among 424 animals (147 cattle and 277 pigs), 131 (30.9%) were contaminated with TCAs, including 69 (16.3%) with chlortetracycline (CTC), 61 (14.4%) with oxytetracycline (OTC), 3 (0.7%) with tetracycline (TC), and 1 (0.2%) with doxycycline (DC) . One sample (cattle kidney) was contaminated with both OTC and DC . The frequencies of OTC and TC residues were significantly higher (p < 0.05) in cattle than in pigs, whereas, the frequency of CTC was significantly higher (p < 0.01) in pigs . Pig kidney samples collected in 1991-1997 had significantly higher incidences of TCAs and CTC (p < 0.01) residues than those in 1985-1986.

J Calif Dent Assoc, 2001 Feb, 29(2), 158 - 69
What the dentist should know about a patient with HIV/AIDS; Lyles AM; Chances are good that oral health care providers will treat someone with diagnosed or undiagnosed HIV during their careers . The Centers for Disease Control and Prevention estimate that 650,000 to 900,000 U.S . residents are living with HIV infection, more than 200,000 of whom are unaware of their infection . As with any medical condition, it is possible for a dentist to do great harm by ignoring systemic manifestations of HIV . On the other hand, dentists who are ignorant of modern HIV disease management often request unnecessary medical consultations resulting in dental treatment delays . Since 1996, the growing use of highly active anti-retroviral therapy and ultrasensitive viral load testing has changed the picture of the dental patient with HIV . The goal of this article is to update and summarize information the oral health care provider needs to safely treat a person with HIV/AIDS . It is not intended to replace previous comprehensive publications on HIV and dentistry, as they are still excellent resources for information . Here, simple instructions for physical evaluation of a patient with HIV/AIDS will be presented and steps for determining safe procedures explained.

Anesth Analg, 2001 May, 92(5), 1237 - 44
The effects of FK506 on neurologic and histopathologic outcome after transient spinal cord ischemia induced by aortic cross-clamping in rats; Lang-Lazdunski L et al.; Spinal cord injury is a devastating complication of thoracoabdominal aortic surgery . We investigated the effect of the immunosuppressant FK506, a macrolide antibiotic demonstrated to have neuroprotective effects in cerebral ischemia models, in a rat model of transient spinal cord ischemia . Spinal cord ischemia was induced in anesthetized rats by using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy . Experimental groups were as follows: sham-operation; control, receiving only vehicle; FK506 A, receiving FK506 (1 mg/kg IV) before clamping; and FK506 B, receiving FK506 (1 mg/kg IV) at the onset of reperfusion . Neurologic status was assessed at 24 h and then daily up to 96 h with a 0 to 6 scale (0, normal function; 6, severe paraplegia) . Rats were randomly killed at 24, 48, or 96 h, and spinal cords were harvested for histopathology . Physiologic variables did not differ significantly among experimental groups . All control rats suffered severe and definitive paraplegia . FK506-treated rats had significantly better neurologic outcome compared with control . Histopathologic analysis disclosed severe injury in the lumbar gray matter of all control rats, whereas most FK506-treated rats had less injury . These data suggest that FK506 can improve neurologic recovery and attenuate spinal cord injury induced by transient thoracic aortic cross-clamping . IMPLICATIONS: A single dose-injection of the immunosuppressant FK506 significantly improved neurologic outcome and attenuated spinal cord injury induced by transient thoracic aortic cross-clamping in the rat.

An Med Interna, 2001 Feb, 18(2), 80 - 3
{Primary actinomycosis of the abdominal wall . Description of 2 cases and review of the literature}; Garcia Garcia JC et al.; We report two cases of isolated abdominal wall actinomycosis and review 18 previously reported cases to further characterize the clinical findings and the therapeutic management of this syndrome . This diagnosis would be advocated in patients with a palpable abdominal mass of subacute appearance with a previous history of digestive medical illness, diabetes, abdominal surgery, or prolonged IUD use . In contrast with other actinomycosis locations, remarkable data were a more elevated mean age of patients; a female predominance; a prevalent location of mass in abdominal lower left quadrant; and a shorter duration of symptomatology before to diagnosis . The CT is the first choice for imaging study and percutaneous needle aspiration would be recommended for definite diagnosis . The long-term antibiotic therapy, with or without percutaneous drainage, is the first treatment choice because is very effective and made unnecessary a more invasive surgical management . The prognosis is excellent with adequated treatment.

J Pak Med Assoc, 2001 Feb, 51(2), 78 - 81
Diabetic foot ulcer--a prospective study; Ali SM et al.; OBJECTIVE: To detect "Feet at Risk" early, its early diagnosis and treatment of foot ulceration to prevent amputation . SETTING AND METHOD: One hundred patients with diabetic foot problems were seen at Baqai Institute of Diabetology and Endocrinology from 06-01-97 to 14-04-99 . Each Patient was examined for peripheral pulses, sensations and reflexes, for dryness of skin, deformity, callus and nail disorders and were photographed on first visit . RESULTS: There were 65% males and 35% females included in this study . Ninety nine patients were type II diabetics, 38% were either smokers or had other addictions (or were addicted to tobacco) . Awareness about risk factors causing foot problems was lacking among all patients . Fifty percent patients were on oral hypoglycaemic agents, 48% were insulin treated, while 2% were on diet and exercise alone . Glycaemic control was poor in 70%, fair in 16% and was good in 14%, 31% were overweight and 5% patients were underweight . Duration of diabetes was greater than ten years in 58%, toes were affected in 44%, sole/metatarsal in 18%; rest included malleoli, heel etc . Eleven patients had ulcers on both feet . Neuropathic ulcer were 42%, neuro ischaemic 58%, Sixty nine percent patients were in the age group between 40-60 years . Cause unknown 29% blisters and boil 14%, trauma/cutting 17%, burns 8%, dry skin/callus 10% . Fundal changes were present in 37%; proteinuria in 37%, ischaemic heart disease in 20%, hypertension 18%, In 60% more than one antibiotic was used . Foot ulcers of fifty nine patients healed on conservative management, six patients had below knee amputation, fifteen had toe amputation; nine were still on treatment, eleven lost contact . CONCLUSION: Lack of awareness, poor glycaemic control and duration of diabetes were the main factors causing diabetic foot problems . This study also confirmed that microvascular complications should be screened in patients with diabetic foot ulcers . Foot care education would be the most important way of dealing with this major problem.

Appl Environ Microbiol, 2001 May, 67(5), 2292 - 7
Applications of gene replacement technology to Streptomyces clavuligerus strain development for clavulanic acid production; Paradkar AS et al.; Cephamycin C production was blocked in wild-type cultures of the clavulanic acid-producing organism Streptomyces clavuligerus by targeted disruption of the gene (lat) encoding lysine epsilon-aminotransferase . Specific production of clavulanic acid increased in the lat mutants derived from the wild-type strain by 2- to 2.5-fold . Similar beneficial effects on clavulanic acid production were noted in previous studies when gene disruption was used to block the production of the non-clavulanic acid clavams produced by S . clavuligerus . Therefore, mutations in lat and in cvm1, a gene involved in clavam production, were introduced into a high-titer industrial strain of S . clavuligerus to create a double mutant with defects in production of both cephamycin C and clavams . Production of both cephamycin C and non-clavulanic acid clavams was eliminated in the double mutant, and clavulanic acid titers increased about 10% relative to those of the parental strain . This represents the first report of the successful use of genetic engineering to eliminate undesirable metabolic pathways in an industrial strain used for the production of an antibiotic important in human medicine.

Endocrinology, 2001 May, 142(5), 2102 - 14
A conditional tetracycline-regulated increase in Gamma amino butyric acid production near luteinizing hormone-releasing hormone nerve terminals disrupts estrous cyclicity in the rat; Bilger M et al.; Gamma amino butyric acid (GABA) is the main inhibitory neurotransmitter controlling LH-releasing hormone (LHRH) secretion in the mammalian hypothalamus . Whether alterations in GABA homeostasis within discrete regions of the neuroendocrine brain known to be targets of GABA action, such as the median eminence, can disrupt the ability of the LHRH releasing system to maintain reproductive cyclicity is not known but amenable to experimental scrutiny . The present experiments were undertaken to examine this issue . Immortalized BAS-8.1 astroglial cells were genetically modified by infection with a regulatable retroviral vector to express the gene encoding the GABA synthesizing enzyme glutamic acid decarboxylase-67 (GAD-67) under the control of a tetracycline (tet) controlled gene expression system . In this system, expression of the gene of interest is repressed by tet and activated in the absence of the antibiotic . BAS-8.1 cells carrying this regulatory cassette, and cultured in the absence of tet ("GAD on"), expressed abundant levels of GAD-67 messenger RNA and GAD enzymatic activity, and released GABA when challenged with glutamate . All of these responses were inhibited within 24 h of exposure to tet ("GAD off") . Grafting "GAD on" cells into the median eminence of late juvenile female rats, near LHRH nerve terminals, did not affect the age at vaginal opening, but greatly disrupted subsequent estrous cyclicity . These animals exhibiting long periods of persistent estrus, interrupted by occasional days in proestrus and diestrus, suggesting the occurrence of irregular ovulatory episodes . Administration of the tetracycline analog doxycycline (DOXY) in the drinking water inhibited GAD-67synthesis and restored estrous cyclicity to a pattern indistinguishable from that of control rats grafted with native BAS-8.1 cells . Animals carrying "GAD on" cells showed a small increase in serum LH and estradiol levels, and a marked elevation in serum androstenedione, all of which were obliterated by turning GAD-67 synthesis off in the grafted cells . Morphometric analysis of the ovaries revealed that both groups grafted with GABA-producing cells had an increased incidence of large antral follicles (>500 micrometer) compared with animals grafted with native BAS-8.1 cells, but that within this category the incidence of steroidogenically more active follicles (i.e . larger than 600 micrometer) was greater in "GAD on" than in "GAD off" rats . These results indicate that a regionally discrete, temporally controlled increase in GABA availability to LHRH nerve terminals in the median eminence of the hypothalamus suffices to disrupt estrous cyclicity in the rat, and raise the possibility that similar local alterations in GABA homeostasis may contribute to the pathology of hypothalamic amenorrhea/oligomenorrhea in humans.

J Capillary Electrophor, 1999 May-Aug, 6(3-4), 131 - 6
Comparisons of the separations of some neutral analytes by LC, MEKC, and CEC; Taylor RB et al.; The relative utility of high-performance liquid chromatography, micellar electrokinetic chromatography (MEKC), and capillary electrochromatography (CEC) is examined for the separation of essentially uncharged solute mixtures . Three model systems are used for which separations by reversed-phase liquid chromatography had been established . These consisted of a set of three substituted hydroxybenzoates; a mixture of six structurally closely related steroids; and the multicomponent aminoglycoside antibiotic, teicoplanin . These sets represented a range of difficulty in achieving separations by reversed-phase LC . It was found that equivalent or better separations for all systems could be established by MEKC and CEC . Both electrophoretic techniques offer much higher peak efficiencies than LC, and MEKC is found to be superior to CEC in terms of peak efficiencies and ruggedness of operation.

Biol Trace Elem Res, 2000 Winter, 78(1-3), 205 - 17
Biological roles of titanium; Yaghoubi S et al.; Ti4+ in soil is a natural antibiotic mobilized by bacteria-generated H+ . When added to the diet of young mice, Ti4+ enhanced their growth . These and observations of others indicate that Ti4+ has a variety of biological roles.

Eur J Obstet Gynecol Reprod Biol, 2001 May, 96(1), 55 - 8
Acyclovir prophylaxis in late pregnancy prevents recurrent genital herpes and viral shedding; Braig S et al.; Neonatal herpes affects about 1 in 15,000 newborns and the prognosis for disseminated disease with encephalitis is poor . We investigated whether acyclovir prophylaxis in late pregnancy effectively reduces the risk of viral shedding and, hence, of mother-to-child transmission at delivery . A prospective study was conducted . Pregnant women who had at least one episode of genital herpes during pregnancy were randomly assigned to two groups: group 1 (n=167) received oral acyclovir from 36 weeks of gestation to term; group 2 (n=121) received no treatment . Group 3 (n=201) comprised women not given prophylaxis who had a history of genital herpes, but no active episodes during pregnancy . No specific instruction were set up for obstetrical management except for cesarean section in case of a suspected herpes lesion at the time of labor . The rate of Cesarean section was 8.4% in group 1, 16.5% in group 2, and 9.9% in group 3 (p<0.001) . 75% of cesareans in group 2 and 10% in group 3 were done for genital herpes . Percentage of viral shedding was, respectively, 0% (group1), 5% (group2), and 0.5%(group3) (p<0.05).These findings underline the value of antiviral prophylaxis in late pregnancy for women with a known history of genital herpes . Such prophylaxis only partly prevents neonatal herpes infection, because it is not applicable to patients with no known clinical history but may excrete the virus.

Biomaterials, 2001 May, 22(9), 897 - 901
Setting characteristics and mechanical behaviour of a calcium phosphate bone cement containing tetracycline; Ratier A et al.; Calcium phosphate cements are used for bone defect filling and they may also be used as delivery systems for active agents . The physicochemical behaviour of an ionic cement, with a final composition of hydroxyapatite, containing tetracycline hydrochloride was investigated . Chemical characterisation, X-ray diffraction analysis, compressive strength and tensile strength were performed . It is known that the antibiotic can be adsorbed on calcium phosphate compounds and the presence of chloride ions can strongly influence the behaviour of the cement . Adding more than 1% (w/w) of 95% pure tetracycline hydrochloride in the solid phase led to a cement with poor mechanical properties, but which, in addition to hydroxyapatite, contained residual starting reagents . For this reason, experiments were also performed with tetracycline previously treated with a calcium sulphate solution . Using a treated tetracycline, it was possible to introduce at least 7% (w/w) of active ingredient whilst still allowing the reaction to proceed to completion i.e . the formation of hydroxyapatite with good mechanical properties . Therefore, treating the tetracycline HCI with calcium sulphate solution prior to reaction conserved the activity of the antibiotic, limited the influence of the antibiotic on the cement evolution and retained the physical properties of the cement.

Int J Med Microbiol, 2001 Mar, 290(8), 669 - 75
Instability and site-specific excision of integration-proficient mycobacteriophage L5 plasmids: development of stably maintained integrative vectors; Springer B et al.; Integrative vectors expressing foreign genes are used as tools for the development of recombinant vaccines in mycobacteria since it is assumed that these vectors are stably maintained even without antibiotic selection . We here demonstrate that integration-proficient vectors are lost from the mycobacterial genome in high frequency . Loss of integrated vectors occurred in recA+ and in recA-strains, indicating a RecA-independent mechanism . Loss of the integrated vector was prevented when integrase gene function was carried on a separate plasmid that is unable to replicate in mycobacteria, indicating that excision is a function of integrase . By providing attP in cis and integrase function in trans, vectors integrating at the attB site are stably maintained, even when carrying genes that deleteriously affect the host.

Minerva Chir, 2000 Dec, 55(12), 847 - 53
{Cervical lymphadenitis caused by mycobacteria . Our experience}; Messina M et al.; BACKGROUND: Mycobacterial infections are extremely complex diseases, either due to the various clinical manifestations, or to the various involved kind of mycobacteria, or to the different sensibility to antibiotics . The authors review retrospectively their series, evaluating the management of pediatric cervical lymphadenitis due to mycobacterical etiology . METHODS: From 1975 to 1998, at the Department of Pediatric Surgery of the university of Siena, 88 children were evaluated for laterocervical lymphadenopathy . Among these, 29 children, aged from 14 months to 13 years, were diagnosed as affected with lymphoadenopathy due to mycobacteria . Therapy of choice was the association of surgery and antibiotics . This behaviour allowed us to approach both advanced lesions, in active colliquation, and progressive ones . RESULTS: Results were unquestionably positive, with a complete resolution and good esthetical results in 93.2% of cases . In 6.8% of cases there was a recurrence, which required reintervention . CONCLUSIONS: On the basis of our series, we agree with the international literature in affirming that, in cases of mycobacterial lymphadenopathy, a combined antibiotic and surgical therapy is necessary . However, controversy about such a complex and difficult pathology is opened and unsolved.

Int J Paediatr Dent, 2000 Sep, 10(3), 237 - 9
Orbital infection arising from a primary tooth: a case report; Rosen D et al.; Odontogenic infections may spread to the orbit by one or more of several paths . Such extension is potentially dangerous and may lead to loss of vision . A case of infection from a primary tooth, which extended to the retrobulbar area is presented in this report . Treatment included surgical drainage of the resulting subperiosteal orbital abscess through a Caldwell-Luc approach as well as aggressive antibiotic therapy . The importance of early suspicion of this entity and its potential sequelae are discussed.

Semin Thorac Cardiovasc Surg, 2001 Jan, 13(1), 13 - 9
Management of postpneumonectomy empyema and bronchopleural fistula; Deschamps C et al.; Empyema after pneumonectomy is often associated with a bronchopleural fistula (BDF) and has a significant mortality . Management options include systemic antibiotics and observation, adequate pleural drainage, appropriate parenteral antibiotics, removal of necrotic tissue, and obliteration of residual pleural space . We prefer to treat the empyema with the procedure originally described by Clagett and Geraci in 1963 . They demonstrated that postpneumonectomy empyema could be successfully treated by open pleural drainage, frequent wet-to-dry dressing changes, and when the thorax was clean, secondary chest wall closure with obliteration of the pleural cavity with an antibiotic solution . Failure was most often caused by a persistent or recurrent fistula . Because of this, when a BPF is present, the original Clagett technique was modified to include transposition of a well-vascularized muscle to cover the stump at the time of open drainage to prevent further ischemia and necrosis . Our preference is intrathoracic transposition of extrathoracic skeletal muscle . The goals of therapy for postpneumonectomy empyema remain a healthy patient with a a healed chest wall and no evidence of drainage or infection . Excellent results can be obtained in more than 80% of patients by using the Clagett procedure and intrathoracic muscle transposition when a BPF is present.

Semin Respir Infect, 2001 Mar, 16(1), 38 - 46
Cytokine treatment of bacterial pneumonia; Nelson S et al.; The lungs represent the largest epithelial surface area of the body and are repeatedly exposed to a variety of potential pathogens . The respiratory system has, therefore, developed an elaborate system of defense mechanisms to maintain the sterility of the lower airways . In the event of a defect, either developmental or acquired of any component of these defenses, the host is rendered susceptible to infection of the respiratory tract . Conventional therapy primarily focuses on the selection of appropriate antibiotic therapy and institution of supportive measures . In this article, we discuss emerging immune-based strategies in the treatment of pneumonia that are primarily focused on amplification of the host defense system through the administration of cytokines.

Semin Respir Infect, 2001 Mar, 16(1), 18 - 26
Gene therapy to modify pulmonary host defenses; Kolls JK et al.; Respiratory infections remain a significant public health problem and are presently the 6th leading cause of death in the United States . Antibiotic-resistant organisms are encountered increasingly in both community-acquired and nosocomial infections . Despite progress in antibiotic development, biological-response modifiers may have increasing application to augment pulmonary host defenses against either drug-resistant infections or in high-risk hosts.Toward this end, gene therapy proposes to deliver biologicals as nucleic acids rather than protein . Gene therapy has the potential advantage of targeting the biological to specific cells or tissue compartments, and a more favorable pharmacokinetic profile . Data on gene delivery and efficacy in preclinical models of pulmonary infection are presented and discussed.

Semin Hematol, 2001 Apr, 38(2 Suppl 3), 11 - 4
Multiple Myeloma . Diagnostic challenges and standard therapy; Kyle RA; In the diagnosis of multiple myeloma (MM), the clinician must exclude other disorders in which a plasma cell reaction may occur such as rheumatoid arthritis and connective tissue disorders, or metastatic carcinoma where the patient may have osteolytic lesions associated with bone metastases . Patients with smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) have none of the complicating features of MM and do not require treatment with potentially toxic agents . The plasma cell labeling index can help make a differential diagnosis of MM from SMM . Patients with a high labeling index have a high risk of complications and should be monitored carefully . However, the labeling index can be low in active MM . In addition, SMM or MGUS patients have few or no circulating plasma cells . High-dose chemotherapy and stem cell support prolong overall survival in contrast to conventional therapy . If stem cell transplantation is considered, it is important to harvest the cells before using alkylating agents to obtain a sufficient number of cells . Supportive treatment consists of the occasional use of erythropoietin to maintain adequate hemoglobin levels and adequate hydration to protect renal function . Vaccination against pneumococcal infections and the prophylactic use of antibiotic therapy during the first 2 months of treatment can be beneficial . Recognizing the symptoms of spinal cord compression and initiating dexamethasone therapy promptly to prevent paraplegia are critical.

Minerva Pediatr, 2001 Feb, 53(1), 39 - 42
{A case of acute lymphoblastic leukemia with an unusual presentation and slow development}; Milanaccio C et al.; The authors describe the case of a 3-year-old girl with acute lymphoblastic leukemia which was diagnosed several months after the appearance of the first symptoms . The delay can be attributed to the vague symptoms at onset in the form of a single laterocervical adenopathy which responded to antibiotic and antiphlogistic therapy, the total absence of any indicative hematological symptoms and the patient s persistent excellent general conditions . In the light of this unusual case, the authors stress the need to carry out invasive diagnostic tests on lymph node lesions that are often defined as aspecific given that they may occasionally disguise more severe lymphoproliferative diseases.

Clin Cancer Res, 2001 Apr, 7(4), 971 - 6
Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo; Vigushin DM et al.; PURPOSE: Trichostatin A (TSA), an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture, is a potent and specific inhibitor of histone deacetylase (HDAC) activity . The purpose of this study was to evaluate the antiproliferative and HDAC inhibitory activity of TSA in vitro in human breast cancer cell lines and to assess its antitumor efficacy and toxicity in vivo in a carcinogen-induced rat mammary cancer model . EXPERIMENTAL DESIGN AND RESULTS: TSA inhibited proliferation of eight breast carcinoma cell lines with mean +/- SD IC(50) of 124.4 +/- 120.4 nM (range, 26.4-308.1 nM) . HDAC inhibitory activity of TSA was similar in all cell lines with mean +/- SD IC(50) of 2.4 +/- 0.5 nM (range, 1.5-2.9 nM), and TSA treatment resulted in pronounced histone H4 hyperacetylation . In randomized controlled efficacy studies using the N-methyl-N-nitrosourea carcinogen-induced rat mammary carcinoma model, TSA had pronounced antitumor activity in vivo when administered to 16 animals at a dose of 500 microg/kg by s.c . injection daily for 4 weeks compared with 14 control animals . Furthermore, TSA did not cause any measurable toxicity in doses of up to 5 mg/kg by s.c . injection . Forty-one tumors from 26 animals were examined by histology . Six tumors from 3 rats treated with TSA and 14 tumors from 9 control animals were adenocarcinomas . In contrast, 19 tumors from 12 TSA-treated rats had a benign phenotype, either fibroadenoma or tubular adenoma, suggesting that the antitumor activity of TSA may be attributable to induction of differentiation . Two control rats each had tumors with benign histology . CONCLUSIONS: The present studies confirm the potent dose-dependent antitumor activity of TSA against breast cancer in vitro and in vivo, strongly supporting HDAC as a molecular target for anticancer therapy in breast cancer.

Ann Thorac Surg, 2001 Apr, 71(4), 1160 - 3
Surgical treatment of Brucella endocarditis; Keles C et al.; BACKGROUND: Brucella endocarditis (BE) is a lethal complication of human brucellosis, which is rarely seen and hardly described . METHODS: In the present report, six successfully treated cases of BE involving three native aortic valves, two native mitral-aortic valves, and a mitral bioprosthesis are described . The diagnosis of BE was based on clinical features, high brucella serologic titers, and positive blood cultures . Although the blood cultures were positive in all patients, all the resected valve materials and tissue cultures were negative . The patients received rifampicin, streptomycin, and doxycycline (in 3 patients), rifampicin, tetracycline, and cotrimoxazole (in 2 patients), and rifampicin, doxycycline, and cotrimoxazole (in 1 patient) . Infected native valves and bioprosthesis were replaced by mechanical valves . RESULTS: There was no early or late mortality . No recurrent infection developed after management with a combination of antibiotherapy lasting 6 months postoperatively during a mean follow-up of 47 months (range 20 to 84 months) . CONCLUSIONS: This report suggests that the combination of valve replacement and antibiotic therapy produces successful results in the treatment of BE.

Rinsho Byori, 2001 Feb, 49(2), 121 - 5
{Helicobacter pylori & gastric disease}; Kozu T et al.; Since the discovery of Helicobacter pylori(H . pylori), causal linkage between H . pylori infection and some of gastric disease has been generally accepted from the results of many studies . Indeed the usefulness of H . pylori eradication therapy for acute gastritis, peptic ulcer, gastric polyp and MALT lymphoma etc . has been reported . In the low grade MALT lymphoma, the regression rate by this therapy is about 70% . On the other hand, we should pay the caution to several adverse effects, such as drug resistance and GERD, of H . pylori eradication therapy . However, based on the several results of comparative studies between antibiotic therapy and the other one, the antibiotic therapy for peptic ulcer is only covered by national health insurance at present . The reversibility of gastric precancerous conditions such as mucosal atrophy, intestinal metaplasia and dysplasia by antibiotic therapy has been studied, but its significance is not clear yet . In animal experiment, H . pylori infection induced gastric adenocarcinoma in Mongolian Gerbils . However, this phenomenon is limited to this kind of animal only . To proof the causal link between H . pylori infection and genesis of gastric cancer in human being, clinical intervention trials are ongoing in the world . If these trials can clarify it, the H . pylori eradication therapy will be established as preventive measure for gastric carcinogenesis.

Chemotherapy, 2001 May-Jun, 47(3), 219 - 25
Ceftriaxone for the treatment of febrile episodes in nonneutropenic patients with hematooncological disease or HIV infection: comparison of outpatient and inpatient care; Egerer G et al.; BACKGROUND: Patients with hematooncological disease or HIV infection and febrile episodes are usually treated in hospital with broad-spectrum antibiotics . The aim of this observational study was to assess the feasibility of ambulatory parenteral antibiotic therapy in hematooncological or HIV-infected patients with confirmed or suspected infection . METHODS: The results in an outpatient treatment group were compared with those obtained in a group initially treated in hospital . Data were gathered on 90 outpatients and 72 inpatients . The inclusion criteria were fever > or =37.5 degrees C with an identified focus of infection, fever > or =38.0 degrees C of suspected bacterial origin with no identified focus of infection, leukocytosis > or =9,000/microl or C-reactive protein elevation > or =10 mg/l . RESULTS: Eighty outpatients and 69 inpatients were evaluable . Treatment in the outpatient group was begun with ceftriaxone . This led to defervescence in 87.5% of cases . The mean treatment duration was 7.1 days . Comparison of results in the outpatients with those initially hospitalized for treatment showed similar success rates . The mean hospital stay in the latter group was 12.9 days . CONCLUSIONS: Ceftriaxone represents an effective treatment for outpatient management of febrile episodes in patients with hematooncological disease or HIV infection . Outpatient treatment is more cost-effective than inpatient care .

J Neurosci, 2001 Apr 15, 21(8), 2580 - 8
Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia; Tikka T et al.; Minocycline, a semisynthetic tetracycline derivative, protects brain against global and focal ischemia in rodents . We examined whether minocycline reduces excitotoxicity in primary neuronal cultures . Minocycline (0.02 microm) significantly increased neuronal survival in mixed spinal cord (SC) cultures treated with 500 microm glutamate or 100 microm kainate for 24 hr . Treatment with these excitotoxins induced a dose-dependent proliferation of microglia that was associated with increased release of interleukin-1beta (IL-1beta) and was followed by increased lactate dehydrogenase (LDH) release . The excitotoxicity was enhanced when microglial cells were cultured on top of SC cultures . Minocycline prevented excitotoxin-induced microglial proliferation and the increased release of nitric oxide (NO) metabolites and IL-1beta . Excitotoxins induced microglial proliferation and increased the release of NO metabolites and IL-1beta also in pure microglia cultures, and these responses were inhibited by minocycline . In both SC and pure microglia cultures, excitotoxins activated p38 mitogen-activated protein kinase (p38 MAPK) exclusively in microglia . Minocycline inhibited p38 MAPK activation in SC cultures, and treatment with SB203580, a p38 MAPK inhibitor, but not with PD98059, a p44/42 MAPK inhibitor, increased neuronal survival . In pure microglia cultures, glutamate induced transient activation of p38 MAPK, and this was inhibited by minocycline . These findings indicate that the proliferation and activation of microglia contributes to excitotoxicity, which is inhibited by minocycline, an antibiotic used in severe human infections.

Cancer Res, 2001 Apr 1, 61(7), 2945 - 52
Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells; Munster PN et al.; 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is an ansamycin antibiotic that binds to a conserved pocket in Hsp90 and induces the degradation of proteins that require this chaperone for conformational maturation . 17-AAG causes a retinoblastoma (RB)-dependent G1 block in cancer cells and is now in clinical trial . In breast cancer cells, G1 block is accompanied by differentiation and followed by apoptosis . The differentiation is characterized by specific changes in morphology and induction of milk fat proteins and lipid droplets . In cells lacking RB, neither G1 arrest nor differentiation occurs; instead, they undergo apoptosis in mitosis . Introduction of RB into these cells restores the differentiation response to 17-AAG . Inhibitors of the ras, mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways cause accumulation of milk fat proteins and induction of lipid droplets when associated with G1 arrest but do not cause morphological changes . Thus, regulation of Hsp90 function by 17-AAG in breast cancer cells induces RB-dependent morphological and functional mammary differentiation . G1 arrest is sufficient for some but not all aspects of the phenotype . Induction of differentiation may be responsible for some of the antitumor effects of this drug.

Chem Biol Interact, 2001 Jan 30, 130-132(1-3), 707 - 22
3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase from Comamonas testosteroni: biological significance, three-dimensional structure and gene regulation; Maser E et al.; 3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) catalyses the oxidoreduction at carbon 3 of steroid hormones and is postulated to initiate the complete mineralisation of the steroid nucleus to CO(2) and H(2)O in Comamonas testosteroni . The enzyme was found to be functional towards a variety of steroid substrates, including the steroid antibiotic fusidic acid . The enzyme also catalyses the carbonyl reduction of non-steroidal aldehydes and ketones such as a novel insecticide . It is suggested that 3alpha-HSD/CR contributes to important defense strategies of C . testosteroni against natural and synthetic toxicants . The 3alpha-HSD/CR gene (hsdA) is 774 base pairs long and the deduced amino acid sequence comprises 258 residues with a calculated molecular mass of 26.4 kDa . A homology search revealed 3alpha-HSD/CR as a new member of the short-chain dehydrogenase/reductase (SDR) superfamily . Upon gel permeation chromatography the purified enzyme elutes as a 49.4 kDa protein indicating a dimeric nature of 3alpha-HSD/CR . The protein was crystallised and the structure solved by X-ray analysis . The crystal structure reveals one homodimer per asymmetric unit, thereby verifying its dimeric nature . Dimerisation takes place via an interface essentially built-up by helix alphaG and strand betaG of each subunit . So far, this type of intermolecular contact has exclusively been observed in homotetrameric SDRs, but never in the structure of a homodimeric SDR . The formation of a tetramer is blocked in 3alpha-HSD/CR by the presence of a predominantly alpha-helical subdomain, which is missing in all other SDRs of known structure . The promoter domain was localised within the 93 bp region upstream of hsdA and the transcriptional start site was identified at 28 bp upstream of the translation start site . Interestingly, hsdA expression was found to be under negative control by two repressor proteins, the genes of which were found in opposite direction downstream or overlapping with hsdA . Based on our results, we propose that induction of hsdA expression in C . testosteroni by steroids actually appears to be a de-repression by preventing the binding of repressor proteins to regulatory regions.

Anal Chem, 2001 Mar 15, 73(6), 1270 - 6
Tandem infrared multiphoton dissociation and collisionally activated dissociation techniques in a quadrupole ion trap; Goolsby BJ et al.; Tandem infrared multiphoton dissociation and collisionally activated dissociation methods are implemented in a quadrupole ion trap mass spectrometer and used to characterize an array of antibiotic ions generated by electrospray ionization . The tandem methods prove useful for probing fragmentation genealogies, evaluating the structures of lower mass fragment ions produced from higher mass molecular ions, and differentiating isobaric ions . The infrared multiphoton dissociation method is more efficient for producing an array of fragment ions over a large mass range, whereas collisionally activated dissociation is preferable for the analysis of lower m/z ions.

Indian J Gastroenterol, 2001 Mar-Apr, 20(2), 59 - 61
Risk factors of persistent diarrhea in children below five years of age; Karim AS et al.; BACKGROUND/OBJECTIVE: Persistent diarrhea is a known cause of childhood mortality, morbidity and malnutrition in developing countries . This study was conducted to find out the host and environmental risk factors associated with persistent diarrhea in Bangladeshi children below 5 years of age . DESIGN: Prospective analytic case-control study . SETTING: Tertiary hospital in Dhaka, Bangladesh . METHODS: Fifty children with persistent diarrhea and 50 controls with acute diarrhea (matched for age and sex) comprised the study subjects . RESULTS: Most of the children (82%) were aged below 2 years . Among the risk factors, Grade III malnutrition (p<0.008), irrational antibiotic use during acute diarrheal episode (p<0.0000005), use of unsafe drinking water (p<0.004) and lack of exclusive breast-feeding up to the first four months of life (p<0.004) were significantly associated with persistent diarrhea . Logistic analysis showed irrational antibiotic use (p<0.0001) during an episode of acute diarrhea and lack of exclusive breast-feeding (p<0.05) during the first four months of life as independent risk factors associated with persistent diarrhea . CONCLUSION: Improvement of nutritional status, encouraging exclusive breast-feeding during the first four months of life, discouraging the irrational use of antibiotic for the treatment of acute diarrhea, and provision of safe drinking water may be important for the prevention of persistent diarrhea as these have been identified as risk factors in Bangladeshi children below five years of age.

Clin Infect Dis, 2001 May 1, 32(9), 1366 - 70 Epub 2001 Apr 03.
Influenza and human immunodeficiency virus infection: absence of HIV progression after acute influenza infection; Golden MP et al.; Influenza is a major cause of morbidity for people with significant underlying disease, but the impact of influenza on people infected with human immunodeficiency virus (HIV) remains unclear . We studied a population of HIV-infected adults during the 1998-1999 influenza season to see whether influenza had any adverse effects on the course of HIV infection . During 5 months of follow-up, we found no unique clinical manifestations or negative impact on CD4(+) cell count, virus load, or clinical progression of HIV disease . Although half of our cohort received antibiotic therapy, none received specific anti-influenza therapy and none required hospitalization . Acute influenza does not appear to be a risk for progression of HIV disease.

Antimicrob Agents Chemother, 2001 May, 45(5), 1561 - 4
Pharmacokinetics of itraconazole oral solution in neutropenic children during long-term prophylaxis; Schmitt C et al.; We investigated the pharmacokinetics and safety of an oral solution of itraconazole in two groups of neutropenic children stratified by age . Effective concentrations of itraconazole in plasma were reached quickly and maintained throughout treatment . The results indicate a trend toward higher concentrations of itraconazole in plasma in older children.

Antimicrob Agents Chemother, 2001 May, 45(5), 1550 - 2
Absence of mutations in marRAB or soxRS in acrB-overexpressing fluoroquinolone-resistant clinical and veterinary isolates of Escherichia coli; Webber MA et al.; The amount of acrB, marA, and soxS mRNA was determined in 36 fluoroquinolone-resistant E . coli from humans and animals, 27 of which displayed a multiple-resistance phenotype . acrB mRNA was elevated in 11 of 36 strains . A mutation at codon 45 (Arg-->Cys) in acrR was found in 6 of these 11 strains . Ten of the 36 isolates appeared to overexpress soxS, and five appeared to overexpress marA . A number of mutations were found in the marR and soxR repressor genes, correlating with greater amounts of marA and soxS mRNA, respectively.

Antimicrob Agents Chemother, 2001 May, 45(5), 1515 - 21
Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutations; Wang H et al.; The genetic basis for fluoroquinolone resistance was examined in 30 high-level fluoroquinolone-resistant Escherichia coli clinical isolates from Beijing, China . Each strain also demonstrated resistance to a variety of other antibiotics . PCR sequence analysis of the quinolone resistance-determining region of the topoisomerase genes (gyrA/B, parC) revealed three to five mutations known to be associated with fluoroquinolone resistance . Western blot analysis failed to demonstrate overexpression of MarA, and Northern blot analysis did not detect overexpression of soxS RNA in any of the clinical strains . The AcrA protein of the AcrAB multidrug efflux pump was overexpressed in 19 of 30 strains of E . coli tested, and all 19 strains were tolerant to organic solvents . PCR amplification of the complete acrR (regulator/repressor) gene of eight isolates revealed amino acid changes in four isolates, a 9-bp deletion in another, and a 22-bp duplication in a sixth strain . Complementation with a plasmid-borne wild-type acrR gene reduced the level of AcrA in the mutants and partially restored antibiotic susceptibility 1.5- to 6-fold . This study shows that mutations in acrR are an additional genetic basis for fluoroquinolone resistance.

J Antibiot (Tokyo), 2001 Feb, 54(2), 153 - 6
Haliangicin, a novel antifungal metabolite produced by a marine myxobacterium . 2 . Isolation and structural elucidation; Fudou R et al.; A novel antifungal antibiotic, haliangicin, was isolated from a culture broth of marine myxobacterium, Haliangium luteum . The planar structure of haliangicin was elucidated by spectroscopic analyses and was shown to be a new polyunsaturated compound containing beta-methoxyacrylate moiety.

Infect Dis Clin North Am, 2001 Mar, 15(1), 123 - 41, ix
Influenza vaccine: issues and opportunities; Neuzil KM et al.; Several recent developments offer opportunities to improve the diagnosis, treatment, and prevention of influenza . Rapid diagnostic tests assist in selecting patients for antiviral therapy and avoid some antibiotic use . The neuraminidase inhibitors now offer therapeutic options with potentially fewer side effects than the traditional drugs, albeit at greater cost . Inactivated influenza vaccine is now recommended annually for all persons aged 50 and older and younger adults and children (aged 6 months and older) who have underlying risk factors for the severe complications of influenza . This includes pregnant women who are in their second or third trimesters during influenza season.

Magy Seb, 2001 Feb, 54(1), 11 - 4
{CT-guided percutaneous drainage in the treatment of acute necrotizing pancreatitis}; Szentkereszty Z et al.; The authors analysed the results of the treatment of 24 patients with acute necrotizing pancreatitis . Besides intensive and operative treatment prophylactic antibiotics, early naso-jejunal feeding, CT guided percutaneous peripancreatic drainage are favourable to avoid septic complications and to postpone the first operation . In 11 patients percutaneous drainage was performed . Using percutaneous drainage three patients (33.3%) recovered without operation, the mean drainage time was 23.4 days . The first operation could be postponed in the other 8 patients after percutaneous drainage . No complications occurred as result of the interventions, although in one patient the drain slipped out spontaneously . Due to the complex treatment the total mortality rate was 12.5%.

Anticancer Res, 2001 Jan-Feb, 21(1B), 605 - 9
Rater agreement and utility of the mutagen-induced chromosome damage assay; McIntyre LM et al.; Chromosomal damage in peripheral blood lymphocytes induced by short-term in vitro exposure to the cytotoxic antibiotic bleomycin was first described in 1983 and proposed as a phenotypic assay for chromosome instability . This assay was subsequently described as potentially useful in assessing an individual's risk to environmental carcinogens in 1989 . Since 1995 numerous published studies have used this assay to assess risk for cancer in the aerodigestive tract, particularly lung cancer, in various ethnic populations . Odds ratios up to 8.5 have been reported for individuals deemed "mutagen sensitive" (defined as > or = 1 chromatid break per metaphase averaged in 50 metaphases analyzed) . While this phenotypic assay is appealing for lung cancer risk assessment it has not been reproduced by other investigators . Because of our interest in lung cancer biology, epidemiology, and genetics, we sought to independently assess the rater agreement of this assay . We found that 1) the assay is laborious to conduct (8 hours of labor) and relatively expensive (> $100), yet reducing the number of metaphases from 50 to 20 produced a reliable, less expensive, and less laborious test; and 2) the rater agreement of individual metaphase readings is poor, but agreement for a summary measure is high.

Magy Seb, 2000 Feb, 53(1), 7 - 12
{Early jejunal feeding in acute pancreatitis: prevention of septic complications and multiorgan failure}; Olah A et al.; Authors evaluate the effect of early jejunal feeding on septic complications and mortality in acute pancreatitis, based on the results of a two-phase, prospective, randomized study . In the first part of the study they compared the conventional parenteral nutrition with early (started within 24 hours) enteral nutrition in a prospective, randomized trial on 89 patients . Forty-eight patients were randomized into the parenteral group "A" (Rindex 10, Infusamin S, Intralipid 10%: 30 kcal/kg) and 41 patients into the enteral group "B" (fed by nasogastric jejunal tube Survimed OPD, 30 kcal/kg) . The rate of septic complications (infected necrosis, abscess, infected pseudocyst) were significantly lower in the enteral group (p = 0.08 chi-square test) . In the second phase of the study early jejunal feeding was combined with imipenem prophylaxis (Tienam, 2 x 500 mg i.v.) in the necrotizing cases detected by CT scan . According to the results of 92 patients the rate of septic complications (p = 0.03), multiple organ failure (p = 0.14), and mortality (p = 0.13) were further reduced in this group . Authors believe that combination of early enteral nutrition and a selective, adequate antibiotic therapy may give a chance for prevention of multiple organ failure.

Br J Perioper Nurs, 2000 Jul, 10(7), 383 - 6
Supportive pharmacology; Griffiths R; We continue to explore the basics of anaesthesia with another article from Rachelle Griffiths, this month looking at supportive pharmacology . If you think this looks too complicated for a Back to Basics piece, read it in small chunks--and be grateful that you are not my spelling checker, which has gone berserk! This Back to Basics series is drawing to a close soon . However, if you have suggestions for any more articles, or perhaps an article itself, then do contact me via Headquarters.

Eur J Anaesthesiol, 2001 Mar, 18(3), 137 - 50
Anaesthetic care for sickle cell disease; Frietsch T et al.; Despite the high frequency of sickle cell disease in Europe, the disease is poorly managed . Critical periods are the hospital stays during which the anaesthesiologist plays an important role . Understanding the molecular basis of polymerization processes of haemoglobin S can help to avoid triggering a crisis . Differentiation of the various haemoglobin phenotypes helps to estimate the individual perioperative risk . Knowledge of the patient's history and the actual haemoglobin S level facilitates general anaesthesia, surgery and postoperative care . Damage to liver, spleen, eyes, bones, lung and central nervous system increases the perioperative risk . Preoperative preparation includes early admission, intravenous volume substitution, continuing pain therapy and prophylactic antibiotic medication . General anaesthesia seems to be better for patients with a high-risk profile rather than regional anaesthesia . Careful perioperative and postoperative monitoring should allow hypoxaemia, hypovolaemia, hypothermia, acidosis and overtransfusion to be avoided . Effective pain therapy includes a combination of opioids with peripherally acting analgesia.

Clin Microbiol Infect, 2001 Feb, 7(2), 70 - 4
The effect of acetazolamide on the kinetics of four newer beta-lactams in the aqueous humor; Voutsinas P et al.; OBJECTIVE: To evaluate whether the effect of acetazolamide on piperacillin's aqueous humor concentrations observed in animals exists also in humans for ceftazidime, cefotaxime, ceftriaxone and aztreonam . METHODS: One hundred and eighty-eight patients undergoing eye cataract surgery were randomly allocated to receive intravenous ceftazidime, cefotaxime, aztreonam or ceftriaxone with (subgroup A) or without (subgroup B) concomitant oral administration of acetazolamide . Antibiotic concentrations in serum and the aqueous humor, simultaneously sampled during the operation, were measured using an agar well diffusion technique, and the ratios of the concentrations of aqueous humor to serum were calculated and compared . Statistical analysis was performed by using the paired t-test . RESULTS: Mean aqueous humor ceftazidime concentrations at 2, 4 and 6 h were 24.65, 16.4 and 8.6 mg/L (subgroup A), and 4.26, 8.66 and 5.61 mg/L (subgroup B) . Corresponding concentrations of cefotaxime were 1.75, 1.0 and 0.77 mg/L (subgroup A), and 1.11, 0.81 and 0.58 mg/L (subgroup B), and of aztreonam 6.9, 5.84 and 3.61 mg/L (subgroup A), and 3.38, 2.57 and 1.48 mg/L (subgroup B) . Ceftriaxone concentrations at 2, 4, 6 and 12 h were 1.78, 1.49, 1.57 and 1.41 mg/L (subgroup A), and 1.35, 0.95, 1.08 and 0.85 mg/L (subgroup B) . The differences in aqueous humor concentrations when acetazolamide was administered were statistically significant (P < 0.05), with the exception of ceftazidime 6 h, cefotaxime 6 h and ceftriaxone 2 h . CONCLUSIONS: Although acetazolamide resulted in statistically significant increases in the aqueous humor concentrations of all the antibiotics tested, this effect was most marked for ceftazidime.

Clin Exp Immunol, 2001 Mar, 123(3), 395 - 401
Activation of signal-transducer and activator of transcription 1 (STAT1) in pouchitis; Kuhbacher T et al.; Activation of signal transducer and activator of transcription 1 (STAT1) is a hallmark of IFN-gamma receptor signal transduction but is also part of the signalling pathway of other cytokines/growth factor receptors . In ulcerative colitis, high levels of activation and expression of STAT1 have been observed in comparison with both Crohn's Disease and normal controls . Pouchitis develops in some patients after Ileal-Pouch-Anal-Anastomosis (IPAA) . The pathophysiology and aetiology of pouchitis is still unclear . Recent studies have shown an increased production of proinflammatory cytokines including IFN-gamma . To investigate the expression and activation of STAT1 in pouchitis and the influence of treatment, patients were followed longitudinally from pouch operation . Diagnosis of pouchitis was made by clinical, endoscopic and histological criteria . Biopsies were obtained during routine endoscopy and snap frozen in liquid nitrogen . Nuclear and cytosolic extracts were prepared and the expression and activation of specific transcription factors were assessed by Western blot, electrophoretic mobility shift assay and immunofluorescence . Patients who develop pouchitis show highly increased levels of STAT1 alpha as well as STAT1 beta expression and activation in comparison with both normal pouch and normal ileal mucosa . Improvement of pouchitis during antibiotic therapy relates to a normalization of STAT1 expression and activation . We conclude that activation of STAT1 correlates to clinical disease activity and therefore STAT1 could play an important role in the pathophysiology of pouchitis . Similarities in the pattern of activation of STAT1 in pouchitis and ulcerative colitis may suggest a common pathway in the immunopathophysiology of both diseases.

J Gen Virol, 2001 May, 82(Pt 5), 1013 - 25
Analysis of the aphthovirus 2A/2B polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal 'skip'; Donnelly ML et al.; The 2A region of the aphthovirus foot-and-mouth disease virus (FMDV) polyprotein is only 18 aa long . A 'primary' intramolecular polyprotein processing event mediated by 2A occurs at its own C terminus . FMDV 2A activity was studied in artificial polyproteins in which sequences encoding reporter proteins flanked the 2A sequence such that a single, long, open reading frame was created . The self-processing properties of these artificial polyproteins were investigated and the co-translational 'cleavage' products quantified . The processing products from our artificial polyprotein systems showed a molar excess of 'cleavage' product N-terminal of 2A over the product C-terminal of 2A . A series of experiments was performed to characterize our in vitro translation systems . These experiments eliminated the translational or transcriptional properties of the in vitro systems as an explanation for this imbalance . In addition, the processing products derived from a control construct encoding the P1P2 region of the human rhinovirus polyprotein, known to be proteolytically processed, were quantified and found to be equimolar . Translation of a construct encoding green fluorescent protein (GFP), FMDV 2A and beta-glucuronidase, also in a single open reading frame, in the presence of puromycin, showed this antibiotic to be preferentially incorporated into the {GFP2A} translation product . We conclude that the discrete translation products from our artificial polyproteins are not produced by proteolysis . We propose that the FMDV 2A sequence, rather than representing a proteolytic element, modifies the activity of the ribosome to promote hydrolysis of the peptidyl(2A)-tRNA(Gly) ester linkage, thereby releasing the polypeptide from the translational complex, in a manner that allows the synthesis of a discrete downstream translation product to proceed . This process produces a ribosomal 'skip' from one codon to the next without the formation of a peptide bond.

Arch Esp Urol, 2001 Jan-Feb, 54(1), 69 - 71
{Genital wound caused by low-speed fire arm}; Gutierrez Garcia R et al.; OBJECTIVE: To report a case of genital gunshot injuries and review the literature . METHODS: A case of low velocity multiple gunshot penile injuries is described . Surgical exploration was performed, gunshot removed and the albuginea repaired . A broad spectrum antibiotic was administered prophylactically for infection . RESULTS: Good cosmetic and functional results, including sexual potency and voiding, were achieved . CONCLUSIONS: Surgical exploration is mandatory in genital gunshot injuries . The best approach to the albuginea is by a crown incision and denudation of the penile skin, which permits surgical repair with excellent cosmetic results.

Masui, 2001 Mar, 50(3), 278 - 80
{A case of wide-spread emphysema following the extraction of mandibular third molar under intravenous sedation}; Matsumoto S et al.; A 45 year-old male underwent lower left third molar extraction under intravenous sedation . During the surgical extraction of the mandibular left impacted third molar using a high-speed air-turbine drill, the patient complained of compression at the level of the right breast without any abnormal vital signs . Radiological investigation and CT scan showed a picture of bilateral, subcutaneous and mediastinal emphysema involving the bilateral face, neck and pectoral area . Following the antibiotic therapy, the drainage was performed through bilateral pectoral incisions by thoracic surgery . The patient recovered within two days and underwent the completion of this surgery under general anesthesia one month later.

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 282 - 5
Applying economic principles to health care; Scott RD 2nd et al.; Applying economic thinking to an understanding of resource use in patient care is challenging given the complexities of delivering health care in a hospital . Health-care markets lack the characteristics needed to determine a "market" price that reflects the economic value of resources used . However, resource allocation in a hospital can be analyzed by using production theory to determine efficient resource use . The information provided by hospital epidemiologists is critical to understanding health-care production processes used by a hospital and developing economic incentives to promote antibiotic effectiveness and infection control.

Emerg Infect Dis, 2001 Mar-Apr, 7(2), 220 - 4
Preventing surgical site infections: a surgeon's perspective; Nichols RL; Wound site infections are a major source of postoperative illness, accounting for approximately a quarter of all nosocomial infections . National studies have defined the patients at highest risk for infection in general and in many specific operative procedures . Advances in risk assessment comparison may involve use of the standardized infection ratio, procedure-specific risk factor collection, and logistic regression models . Adherence to recommendations in the 1999 Centers for Disease Control and Prevention guidelines should reduce the incidence of infection in surgical patients.

J Infect Dis, 2001 May 1, 183(9), 1409 - 12 Epub 2001 Apr 10.
Survival of patients with AIDS, after diagnosis of Pneumocystis carinii pneumonia, in the United States; Dworkin MS et al.; To examine survival after diagnosis of Pneumocystis carinii pneumonia (PCP) and factors associated with early death (during the month of or the month after diagnosis of PCP), data were analyzed from the Adult and Adolescent Spectrum HIV Disease project . Among 4412 patients with 5222 episodes of PCP during follow-up (1992-1998), survival at >1 month after diagnosis was 82%, and survival at > or =12 months after diagnosis was 47%; 12-month survival increased from 40% in 1992-1993 to 63% in 1996-1998 . By multiple logistic regression analysis, early death was associated with history of PCP (odds ratio {OR}, 1.4), age 45-59 years (OR, 1.9) or > or =60 years (OR, 3.7), and CD4 cell count of 0-24 cells/microL (< or =5 months before PCP; OR, 1.8) or 25-49 cells/microL (OR, 1.4) (P<.05) . Concurrent prescription of combination antiretroviral therapy (OR, 0.2) and other antiretroviral therapy (OR, 0.4) was associated with surviving the early period . This study shows improved survival after diagnosis of PCP in recent years, despite emergence of antibiotic-resistant mutant P . carinii strains.

Rev Med Liege, 2001 Feb, 56(2), 93 - 6
{Lyme disease and facial paralysis in children}; Tuerlinckx D et al.; Lyme disease is one of the most common cause of acute peripheral facial palsy in children . Overall nervous system involvement is also the predominant manifestation of Lyme disease in children, chiefly as facial palsy and/or aseptic meningitis . The medical records of ten patients with discharge diagnosis of facial palsy associated to borreliosis were retrospectively reviewed . The diagnostic criteria for borreliosis included acute peripheral facial palsy associated with erythema migrans (1/10) and/or positive Lyme serology in serum (10/10) or CSF (6/10) . Facial palsy was associated with a high rate (9/10) of occult meningitis . Cerebrospinal fluid findings showed lymphocytic pleocytosis associated to moderate increased protein level . PCR assays displayed a very low sensitivity . All patients with meningitis were treated with intravenous ceftriaxone for 3 weeks and received their treatment as outpatients with an heparinised venous catheter . Our study confirm that borreliosis should be considered in every case of peripheral facial palsy and based on the high rate of occult meningitis, we also advocate to perform a lumbar puncture . Although long term prognosis of facial palsy associated with Lyme disease in children appears excellent, current treatment recommendations advocate prolonged antibiotic therapy.

Clin Microbiol Rev, 2001 Apr, 14(2), 296 - 326
Leptospirosis; Levett PN; Leptospirosis is a worldwide zoonotic infection with a much greater incidence in tropical regions and has now been identified as one of the emerging infectious diseases . The epidemiology of leptospirosis has been modified by changes in animal husbandry, climate, and human behavior . Resurgent interest in leptospirosis has resulted from large outbreaks that have received significant publicity . The development of simpler, rapid assays for diagnosis has been based largely on the recognition that early initiation of antibiotic therapy is important in acute disease but also on the need for assays which can be used more widely . In this review, the complex taxonomy of leptospires, previously based on serology and recently modified by a genotypic classification, is discussed, and the clinical and epidemiological value of molecular diagnosis and typing is also evaluated.

Int J Pharm, 2001 Apr 17, 217(1-2), 57 - 69
Gentamicin bone cements: characterisation and release (in vitro and in vivo assays); Torrado S et al.; Due to the extended use of acrylic bone cements, its necessary to develop improved formulations in order to resolve their many drawbacks . The present work was conducted to make a physical-chemical characterisation of this kind of acrylic cement in order to introduce future changes in the formulations to: (1) improve or at least maintain their mechanical properties; (2) diminish their toxicity, and (3) control the drug release (rate and amount) . From the dissolution method we can conclude that the preparation method (with or without pressure) of specimens is not responsible for the erratic release . The cumulative amount of gentamicin released was fitted to a semi-empirical equation to explain the possible release mechanism . The powder size, shape and distribution that could affect several properties of bone cement were studied with the aid of different techniques such as SEM, laser diffraction spectroscopy, and powder X-ray diffraction . From SEM micrographs, it was possible to observe that the surfaces of the specimens were very irregular with numerous small craters that may serve as conduits for eluting the antibiotic . An 'in vitro' drug diffusion model is proposed to elucidate the drug release mechanism . Finally an 'in vivo' study was performed to evaluate the antibiotic release to the neighbouring bone sites.

Eur Respir J, 2000 Dec, 16(6), 1142 - 6
Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing; Esposito S et al.; In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae in reactive airway disease, 71 children aged 2-14 yrs with an acute episode of wheezing and 80 age-matched healthy children were studied . Sera for the determination of specific antibody levels and nasopharyngeal aspirates for the detection of M . pneumoniae and C . pneumoniae deoxyribonucleic acid were obtained on admission and after 4-6 weeks . All children with wheezing received a standard therapy with inhaled corticosteroids and bronchodilators for 5-7 days; when antibiotic was added on the basis of the judgement of the paediatrician in charge, clarithromycin 15 mg.kg body weight(-1).day(-1) for 10 days was used . Acute M . pneumoniae and C . pneumoniae infections were detected significantly more often in children with wheezing than in controls . In patients infected with one of the two pathogens, a history of recurrent wheezing was significantly more frequent than in those without either infection . During a 3-month follow-up period, among nonantibiotic-treated children, those with acute M . pneumoniae and/or C . pneumoniae infection showed a significantly higher recurrence of wheezing than those without acute M . pneumoniae and/or C . pneumoniae infection (p=0.03) . These results highlight the apparently significant relationship of Mycoplasma pneumoniae and Chlamydia pneumoniae with wheezing in children, particularly in subjects with a history of recurrent episodes, and the possible improvement in the course of reactive airway disease within paediatric patients with acute Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection.

Kobe J Med Sci, 2000 Jun, 46(3), 137 - 45
Establishment of a novel human squamous cell carcinoma cell line from oral primary tumor by geneticin treatment; Ji ZW et al.; A novel cultured cell line NOS-1, derived from a human oral primary squamous cell carcinoma (SCC) of the lower gingiva, was established without xenografting the tumor into nude mice by means of "Geneticin" treatment, which allowed for elimination of contaminated fibroblasts and produced enriched tumor cells at an early stage of the culture . NOS-1 cells showed numerous desmosome structures and some intermediate filaments . To determine tumorigenicity and to establish an orthotopic tissue invasion model for oral carcinoma, the NOS-1 cells were injected into the back and the tongue of male athymic nude mice . The back tumors showed an expansive growth pattern without significant invasion of surrounding tissues, while the tongue-implanted tumors exhibited invasive growth . The establishment of a novel oral primary tumor cell line and a new orthotopic tissue invasion model is expected to be useful for the study of biological characterization and for the identification of the invasive mechanism of human oral cancers.

Sex Transm Dis, 2001 Mar, 28(3), 184 - 6
Pedal interdigital condylomata lata: a rare sign of secondary syphilis; Rosen T et al.; BACKGROUND: Condylomata lata of the toe webs are uncommon manifestations of secondary syphilis . Considering the recent decline in the incidence of syphilis in the United States, such lesions are likely to present infrequently . In some cases, this phenomenon may be the only physical sign of syphilis; therefore, it is important that a high index of suspicion is maintained when evaluating toe web lesions in patients at epidemiologic risk for syphilis . GOALS: A case of secondary syphilis presenting solely with interdigital condyloma lata in the toe web spaces is reported, and similar cases reported in the literature are reviewed . STUDY DESIGN: This article documents the diagnosis of secondary syphilis based on a positive serology in conjunction with the development of interdigital condyloma lata as the only physical finding suggestive of lues . RESULTS: The latter lesions resolved after appropriate, adequate antibiotic therapy . CONCLUSIONS: A case of condylomata lata of the toe webs without other pertinent physical findings is presented . Analogous to lesions typically seen in the anogenital region, moist exophytic toe web plaques may represent condyloma lata and thereby be a sign of secondary syphilis . The differential diagnosis includes tinea pedis, erythrasma, macerated corns, verrucae, and several tropical mycoses (chromomycosis, mycetoma).

Akush Ginekol (Sofiia) . 2000;40(4):53.
{Prophylaxis of postabortion endometriosis with Cedax}; Mazneikova V et al.; The authors investigate the possibilities for antibiotic prophylactics of postabortion endometritis with the drug Cedax in high risk patients.

Am J Infect Control, 2001 Apr, 29(2), 73 - 8
Research Priorities Project, year 2000: establishing a direction for infection control and hospital epidemiology; Lynch P et al.; BACKGROUND: The field called "infection control" has expanded beyond hospitals to include many health care locations, some aspects of personnel health, elements of noninfectious complications, and occasionally the epidemiology of other problems that occur in care facilities . A research agenda that addresses these newer segments and provides a framework for answering fundamental questions is essential for the field and for the work of The Research Foundation for Prevention of Complications Associated with Health Care (formerly APIC Research Foundation) . METHODS: We used a multiple-round iterative consensus process (Delphi technique) with 50 experts and a validation round among participants at the 4th Decennial Conference . RESULTS: The expert panel reduced 102 separate items to 21 high-ranked research priorities . The highest-ranked subject areas involved research to improve compliance with excellent practices, to study antibiotic usage and resistance, to measure the financial impact of complications and value of interventions, to perform surveillance of infectious and noninfectious complications across the spectrum of care delivery, and to study effectiveness of interventions to prevent complications at specific sites . There were differences in education and discipline between the expert panel and the 4th Decennial participants and with respect to ranking some of the individual priorities . Among respondents from outside the United States and Canada, occupational health issues were ranked more highly . CONCLUSIONS: The research priorities provide a blueprint for future progress and will require a collaborative, multicenter, multinational approach.

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