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