Plast Reconstr Surg, 1997 Apr, 99(5), 1324 - 8 The fate of preserved autogenous bone graft; DeLuca L et al.; Certain clinical conditions exist in which a section of cranial bone is removed but not immediately replaced at the initial procedure . Preservation of this bone can provide a valuable autogenous donor source for a future reconstructive procedure . The purpose of our study was to compare the volume retention of fresh autogenous bone with that of preserved autogenous bone as inlay and onlay cranial grafts . Two bone grafts were harvested from the skull of 15 adult New Zealand White rabbits . The graft volumes were calculated, and the graft were preserved in a normal saline-antibiotic solution at -20 degrees C . Three months later, during the second procedure, a fresh graft was harvested and then placed in the preexisting occipital defect as an inlay graft . Also at this time, the preserved grafts were placed, one as an inlay graft in the fresh occipital defect and the other as an onlay graft in the frontal region . The animals were sacrificed 3 months later, and the percentage of graft volume retention was determined . The fresh inlay grafts had a mean volume retention of 85.1 percent, while the preserved inlay nad onlay grafts had 61.8 and 75.9 percent mean volume retention, respectively . It is concluded that while fresh cranial autograft remains the "gold standard" for craniofacial reconstruction, preserved autogenous cranial bone is a viable alternative for inlay and onlay grafting of the craniofacial region. Ophthalmic Surg Lasers, 1997 Apr, 28(4), 321 - 4 New ophthalmic manifestations of presumed rifabutin-related uveitis; Arevalo JF et al.; Rifabutin-related uveitis has been reported in AIDS patients who take a daily dose of 300 to 1800 mg of this drug . Presumed rifabutin-related uveitis is characterized by unilateral or bilateral anterior chamber inflammation with hypopyon accompanied by hyperemia, pain, photophobia, and vitritis . However, retinal manifestations or vitreous cytology of this entity have never been reported . This report describes a patient who had retinal vascular changes associated with uveitis while being treated with oral rifabutin . Fundus photographs and fluorescein angiograms documented resolved retinal vasculitis . Vitreous cytology of this case showed acute inflammatory cells . To the authors' knowledge, this is the first report of retinal vasculopathy in a patient with rifabutin-related uveitis and the first analysis of the vitreous cytologic aspects of this disease. J Bacteriol, 1997 Apr, 179(8), 2668 - 77 Transposon mutagenesis reinforces the correlation between Mycoplasma pneumoniae cytoskeletal protein HMW2 and cytadherence; Krause DC et al.; A new genetic locus associated with Mycoplasma pneumoniae cytadherence was previously identified by transposon mutagenesis with Tn4001 . This locus maps approximately 160 kbp from the genes encoding cytadherence-associated proteins HMW1 and HMW3, and yet insertions therein result in loss of these proteins and a hemadsorption-negative (HA-) phenotype, prompting the designation cytadherence-regulatory locus (crl) . In the current study, passage of transformants in the absence of antibiotic selection resulted in loss of the transposon, a wild-type protein profile, and a HA+ phenotype, underscoring the correlation between crl and M . pneumoniae cytadherence . Nucleotide sequence analysis of crl revealed open reading frames (ORFs) orfp65, orfp216, orfp41, and orfp24, arranged in tandem and flanked by a promoter-like and a terminator-like sequence, suggesting a single transcriptional unit, the P65 operon . The 5' end of orfp65 mRNA was mapped by primer extension, and a likely promoter was identified just upstream . The product of each ORF was identified by using antisera prepared against fusion proteins . The previously characterized surface protein P65 is encoded by orfp65, while the 190,000 Mr cytadherence-associated protein HMW2 is a product of orfp216 . Proteins with sizes of 47,000 and 41,000 Mr and unknown function were identified for orfp41 and orfp24, respectively . Structural analyses of HMW2 predict a periodicity highly characteristic of a coiled-coil conformation and five leucine zipper motifs, indicating that HMW2 probably forms dimers in vivo, which is consistent with a structural role in cytadherence . Each transposon insertion mapped to orfp216 but affected the levels of all products of the P65 operon . HMW2 is thought to form a disulfide-linked dimer, formerly designated HMW5, and examination of an hmw2 deletion mutant confirms that HMW5 is a product of the hmw2 gene. Biochemistry, 1997 Apr 1, 36(13), 3917 - 29 DNA cleavage by topoisomerase I in the presence of indolocarbazole derivatives of rebeccamycin; Bailly C et al.; DNA topoisomerase I has been shown to be an important therapeutic target in cancer chemotherapy for the camptothecins as well as for indolocarbazole antibiotics such as BE-13793C and its synthetic derivatives NB-506 and ED-110 {Yoshinari et al . (1993) Cancer Res . 53, 490-494} . To investigate the mechanism of topoisomerase I inhibition by indolocarbazoles, we have studied the induction of DNA cleavage by purified mammalian topoisomerase I mediated by the antitumor antibiotic rebeccamycin and a series of 20 indolocarbazole derivatives . The compounds tested bear (i) various functional groups on the non-indolic moiety (X = CO, CH2, CHOH), (ii) a hydrogen or a chlorine atom at positions 1 and 11 (R2), and (iii) different substituents on the maleimido function (R1 = H, OH, NH2, NHCHO) . Half of the ligands have the same carbohydrate moiety as rebeccamycin whereas the other ligands have no sugar residue . The inhibitory potency of the test compounds was assessed in vitro by comparing the cleavage of {32P}-labeled restriction fragments by the enzyme in the absence and presence of the drug . In addition, the DNA-binding properties of these compounds were investigated by means of complementary spectroscopic techniques including electric linear dichroism, and the DNA sequence selectivity was probed by DNase I footprinting . The study shows that the sugar residue attached to the indolocarbazole chromophore is critical for the drug ability to interfere with topoisomerase I as well as for the formation of intercalation complexes . Structure-activity relationships indicate that the presence of chlorine atoms significantly reduces the effects on topoisomerase I whereas the substituents on the maleimido function and the functional group on the non-indolic moiety can be varied without reduction of activity . The results suggest that the inhibition of topoisomerase I by indolocarbazoles arises in part from their ability to interact with DNA . Analysis of the base preferences around topoisomerase I cleavage sites in various restriction fragments indicated that, in a manner similar to camptothecin, the rebeccamycin analogue R-3 stabilized topoisomerase I preferentially at sites having a T and a G on the 5' and 3' sides of the cleaved bond, respectively . By analogy with models previously proposed for camptothecin and numerous topoisomerase II inhibitors which intercalate into DNA, a stacking model for the interaction between DNA, topoisomerase I and indolocarbazoles is proposed . These findings provide guidance for the development of new topoisomerase I-targeted antitumor indolocarbazole derivatives. Ann Intern Med, 1997 Apr 1, 126(7), 520 - 7 Diagnosis and monitoring of Whipple disease by polymerase chain reaction; Ramzan NN et al.; BACKGROUND: Whipple disease is a chronic, multisystem disorder associated with infection with Tropheryma whippelii, an organism that has not yet been grown on artificial media . In some cases, the diagnosis of Whipple disease is uncertain if it is based on histology alone . Although antibiotic regimens of various durations have been used, the disease recurs in about one third of cases . No test for cure is available . OBJECTIVE: To develop a test that is more sensitive and specific than histologic examination to diagnose Whipple disease and monitor the effects of antibiotic therapy . DESIGN: Retrospective, laboratory-based evaluations of stored tissue specimens . PATIENTS: 30 patients with clinically diagnosed, histologically confirmed Whipple disease and 8 patients in whom Whipple disease was clinically suspected but who did not have definitive histologic evidence . MEASUREMENTS: Pretreatment and post-treatment biopsy specimens of the small bowel and lymph node were tested by polymerase chain reaction for the presence of T . whippeli DNA . RESULTS: Results on PCR were positive in 29 of the 30 specimens from patients with histologically confirmed disease (sensitivity, 96.6%; specificity, 100%) and in 7 of the 8 specimens from patients in whom disease was clinically suspected . Small-bowel biopsy specimens were obtained after treatment from 17 patients (median duration of follow-up, 119 months); specimens from 12 of these patients had positive results on PCR . When these cases were correlated with therapeutic outcome, it was found that 7 of the 12 patients had clinical relapse during subsequent follow-up or had never responded to treatment (positive predictive value, 58% {95% CI, 28% to 85%}) . In contrast, none of the 5 patients whose post-treatment biopsy specimens had negative results on PCR had relapse (negative predictive value, 100% {CI, 48% to 100%}; P = 0.044) . No correlation was found between post-treatment histology and clinical outcome (P > 0.2) . CONCLUSIONS: Polymerase chain reaction is highly sensitive and specific when used to confirm the diagnosis of Whipple disease, to identify inconclusive and suspicious cases, and to monitor response to therapy . A negative result on PCR may predict a low likelihood of clinical relapse; a positive test result that remains positive despite therapy may be associated with a poor clinical outcome . Histopathologic evaluation of post-treatment specimens does not predict clinical cure or relapse. Antimicrob Agents Chemother, 1997 Apr, 41(4), 752 - 6 Activity of liposomal amphotericin B against experimental cutaneous leishmaniasis; Yardley V et al.; The polyene antibiotic amphotericin B is currently a second-line treatment for visceral leishmaniasis (VL) and mucocutaneous leishmaniasis . Lipid-amphotericin B formulations with lower toxicity than the parent drug that were developed for the treatment of systemic mycoses have proved to be an effective treatment for VL, especially AmBisome, a small unilamellar negatively charged liposome . In vitro, free amphotericin B was three to six times more active than the liposomal formulation AmBisome against both Leishmania major promastigotes in culture and amastigotes in murine macrophages . In a BALB/c L . major model of cutaneous infection, liposomal amphotericin B administered once a day on six alternate days by the intravenous route produced a dose-response effect between 6.25 and 50 mg/kg . Liposomal amphotericin B administered subcutaneously close to a lesion had no significant activity . Free drug was ineffective at nontoxic doses . The results suggest that liposomal amphotericin B may be useful in the treatment of cutaneous leishmaniasis. Hum Gene Ther, 1997 Mar 20, 8(5), 555 - 61 Intracellular delivery of lipopolysaccharide during DNA transfection activates a lipid A-dependent cell death response that can be prevented by polymyxin B; Cotten M et al.; The presence of lipopolysaccharide (LPS) as a contaminant in plasmid DNA prepared from Escherichia coli is well documented, and we have previously demonstrated that LPS internalization during adenovirus-mediated gene transfer can generate a toxicity in some primary cell types . We demonstrate here that in addition to adenoviral systems, several commonly used nonviral methods of gene transfer also activate this cell death response in the presence of LPS . Subcomponents of LPS were analyzed and the toxicity was found to be due to the lipid A component of LPS . The LPS-chelating antibiotic polymyxin B, when present at concentration of 10-30 micrograms/ml, can block this toxicity. Biochemistry, 1997 Mar 18, 36(11), 3050 - 5 Fosfomycin resistance protein (FosA) is a manganese metalloglutathione transferase related to glyoxalase I and the extradiol dioxygenases; Bernat BA et al.; The enzyme conferring resistance to the antibiotic fosfomycin {(1R,2S)-1,2-epoxypropylphosphonic acid} originally reported by Suarez and co-workers {Area, P., Hardisson, C., & Suarez, J . E . (1990) Antimicrob . Agents Chemother . 34, 844-848} is demonstrated in this study to be a metalloglutathione transferase . The apoenzyme is a dimer of 16 kDa subunits . Electron paramagnetic resonance spectroscopy and water proton nuclear magnetic resonance longitudinal relaxation rates suggest that each subunit contains a mononuclear Mn2+ center that interacts strongly with the substrate fosfomycin (Kd = 17 microM) more weakly with the product (Kd = 1.1 mM) and very weakly or not at all with GSH . Inhomogeneous broadening of the EPR signals of enzyme-bound Mn2+ in the presence of H2(17)O indicates that three of the coordination sites on the metal are occupied by water . Sequence alignments, three-dimensional structures, and mechanistic considerations suggest that FosA is related to at least two other metalloenzymes, glyoxalase I and the Mn2+- or Fe2+-containing extradiol dioxygenases . The mechanistic imperative driving the evolution of this previously unidentified superfamily of metalloenzymes is proposed to be bidentate coordination of a substrate or intermediate to the metal center in the enzyme-catalyzed reactions. Nucleic Acids Res, 1997 Mar 15, 25(6), 1219 - 24 Interaction of tetracycline with RNA: photoincorporation into ribosomal RNA of Escherichia coli; Oehler R et al.; Photolysis of {3H}tetracycline in the presence of Escherichia coli ribosomes results in an approximately 1:1 ratio of labelling ribosomal proteins and RNAs . In this work we characterize crosslinks to both 16S and 23S RNAs . Previously, the main target of photoincorporation of {3H}tetracycline into ribosomal proteins was shown to be S7, which is also part of the one strong binding site of tetracycline on the 30S subunit . The crosslinks on 23S RNA map exclusively to the central loop of domain V (G2505, G2576 and G2608) which is part of the peptidyl transferase region . However, experiments performed with chimeric ribosomal subunits demonstrate that peptidyltransferase activity is not affected by tetracycline crosslinked solely to the 50S subunits . Three different positions are labelled on the 16S RNA, G693, G1300 and G1338 . The positions of these crosslinked nucleotides correlate well with footprints on the 16S RNA produced either by tRNA or the protein S7 . This suggests that the nucleotides are labelled by tetracycline bound to the strong binding site on the 30S subunit . In addition, our results demonstrate that the well known inhibition of tRNA binding to the A-site is solely due to tetracycline crosslinked to 30S subunits and furthermore suggest that interactions of the antibiotic with 16S RNA might be involved in its mode of action. BMJ, 1997 Mar 8, 314(7082), 722 - 7 Open randomised trial of prescribing strategies in managing sore throat; Little P et al.; OBJECTIVE: To assess three prescribing strategies for sore throat . DESIGN: Randomised follow up study . SETTING: 11 general practices in the South and West region . SUBJECTS: 716 patients aged 4 years and over with sore throat and an abnormal physical sign in the throat; 84% had tonsillitis or pharyngitis . Patients were randomised to three groups: prescription for antibiotics for 10 days (group 1,246 patients); no prescription (group 2,230 patients); or prescription for antibiotics if symptoms were not starting to settle after three days (group 3; 238 patients) . MAIN OUTCOME MEASURES: Duration of symptoms; satisfaction and compliance with and perceived efficacy of antibiotics; time off school or work . Outcomes were documented in 582 subjects (81%) . RESULTS: Median duration of antibiotic use differed significantly in the three groups (10 v 0 v 0 days, P < 0.001); 69% of patients in group 3 did not use their prescription . The proportion of patients better by day 3 did not differ significantly (37% v 35% v 30%, P = 0.28), nor did the duration of illness (median 4 v 5 v 5 days, P = 0.39), days off work or school (median 2 v 2 v 1, P = 0.13), or proportion of patients satisfied (96% v 90% v 93%, P = 0.09), although group 1 had fewer days of fever (median 1 v 2 v 2 days, P = 0.04) . More patients in group 1 thought the antibiotics were effective (87% v 55% v 60%, P < 0.001) and intended coming to the doctor in future attacks (79% v 54% v 57%, P < 0.001) . "Legitimation" of illness-to explain to work or school (60%) or family or friends (37%)-was an important reason for consultation . Patients who were more satisfied got better more quickly, and satisfaction related strongly to how well the doctor dealt with patient's concerns . CONCLUSION: Prescribing antibiotics for sore throat only marginally affects the resolution of symptoms but enhances belief in antibiotics and intention to consult in future when compared with the acceptable strategies of no prescription or delayed prescription . Psychosocial factors are important in the decision to see a general practitioner and in predicting the duration of illness. Virology, 1997 Mar 3, 229(1), 228 - 39 Construction and characterization of herpes simplex virus type 1 mutants with conditional defects in immediate early gene expression; Preston CM et al.; The herpes simplex virus type 1 (HSV-1) mutant in 1814 contains an insertion mutation in the coding sequence for the virion transactivator protein VP16 and is thus impaired for the activation of immediate early (IE) gene expression . This virus was modified further by introducing the Moloney murine leukemia virus LTR promoter in place of the upstream sequences controlling expression of the IE regulatory protein ICPO, to yield mutant in 1820 . In almost all cell types tested, in 1820 initiated infection less efficiently than in 1814, behaving as if lacking both VP16 and ICPO functions, but in BHK cells in 1820 was less impaired than in 1814 . A rescuant of in 1820 at the VP16 locus, in 1825, also exhibited a host range phenotype, initiating replication as efficiently as wild-type HSV-1 in BHK cells but inefficiently in other cell types . In 1825 was unable to complement an ICPO null mutant in restricted cells, demonstrating that the promoter exchange prevented the expression of ICPO protein in functionally significant amounts . The novel host range properties of in 1820 provided a basis for the construction of additional viruses conditionally impaired for IE gene expression and assessment of their value as prototype vectors . Production of an HSV-1 mutant multiply defective in the expression of IE gene products was achieved by introduction of the temperature-sensitive mutation of HSV-1 tsK, which inactivates the IE transcription activator ICP4 at nonpermissive temperatures, into in 1820 to produce in 1820K . This mutant could be propagated effectively in BHK cells at 31 degrees but was effectively devoid of the major regulators ICPO, ICP4, and VP16 in other cells types at 38.5 degrees . Cultures could withstand infection with 5 PFU of in 1820K per cell without detectable cytopathology and could be reseeded to form colonies at approximately 90% efficiency . A derivative of in 1820K containing the Escherichia coli lacZ gene controlled by the human cytomegalovirus (HCMV) major IE promoter expressed low but detectable levels of beta-galactosidase in almost all cells after infection of cultures at 5 PFU per cell and incubation at 38.5 degrees . Cultures infected with 5 PFU per cell of an in 1820K derivative expressing neomycin phosphotransferase (npt) controlled by the HCMV IE promoter were resistant to killing by the antibiotic G418 for up to 3 days, and cell survival correlated with the retention of functional levels of npt . Mutants based on in 1820K can thus express foreign gene products in virtually all cells in a culture under conditions in which cytotoxicity is eliminated, demonstrating that progressive reduction of IE gene expression is an important step in the design of HSV-1-derived vectors. J Card Surg, 1997 Mar-Apr, 12(2 Suppl), 256 - 60; discussion 260-1 The infected aorta; von Segesser LK et al.; BACKGROUND: Despite the improvements achieved in antibiotic therapy, severe aortic infection resulting in mycotic aneurysms is still a highly lethal disease and surgical management remains a challenging task . PATIENTS AND METHODS: A total of 43 patients with severe aortic infections were analyzed and separated in four groups: (1) Infections of the aortic root Ventriculo-aortic disconnection due to deep aortic infection (6 patients) . Two patients were operated using homo-composit grafts . Of the 6 patients total, one died early and two died late during a mean follow-up of 6 years . The two patients with homografts are still alive . (2) Infections of the ascending aorta and the aortic arch . In situ repair for mycotic aneurysmal lesions of the ascending aorta was performed in 6 patients using synthetic graft material in 4/6, biological material in 1/6 and direct suture in 1/6 . Two patients had to be reoperated; one of them died early . There was no recurrent infection during a mean follow-up of 6 years . (3) Infections of the descending thoracic and thoraco-abdominal aorta in-situ repair for mycotic aneurysmal lesions of the descending and thoraco-abdominal aorta was performed in 12 patients using homografts in five . Two patients died early and two other patients died late during a mean follow-up of 6 years . (4) Infections of the infrarenal abdominal aorta . In this series of 19 patients with mycotic infrarenal aortic aneurysms, in situ reconstruction was performed in 12 (5/12 with homografts) and extra-anatomic reconstruction (axillo-femoral bypass) was performed in 7 . Hospital mortality was 5/19 patients and another 5/19 patients died during a mean follow-up of 6 years . One of the early deaths was due to aortic stump rupture . Two patients with axillo-femoral reconstructions were later converted to descending-thoracic-aortic-bifemoral bypasses . Five thromboses of axillo-femoral bypasses were observed in three of the seven patients with extra-anatomic repairs . RESULTS: Infections of the aortic root, the ascending aorta and the aortic arch are approached with total cardio-pulmonary bypass, using cardioplegic myocardial protection and deep hypothermia with circulatory arrest if necessary . Proximal unloading and distal support using partial cardiopulmonary bypass is preferred for repair of infected descending and thoracoabdominal aortic lesions, whereas no such adjuncts are required for repair of infected infrarenal aortic lesions . CONCLUSIONS: The anatomical location of the aortic infection and the availability of homologous graft material are the main factors determining the surgical strategy. Vestn Oftalmol, 1997 Mar-Apr, 113(2), 19 - 21 {Clinical and laboratory assessment of therapeutic efficacy of maxaquin in treatment of chlamydial conjunctivitis}; Maichuk IF et al.; Maxaquin (lomefloxacin), a new fluoroquinolone antibiotic, was used in combined therapy of chlamydial conjunctivitis . The results of treatment of 72 patients were assessed by the clinical manifestations and the laboratory time course of Chlamydia trachomatis antigen in smears from the conjunctiva, detected by enzyme immunoassay . Clinical and laboratory findings proved the high efficacy of the drug and its advantages over traditional therapy and other fluoroquinolones. Mikrobiol Z, 1997 Mar-Apr, 59(2), 20 - 4 {The induction of mutations in Streptomyces aureofaciens by UV rays and nitrosoguanidine and the identification of the mutants obtained}; Lavrinchuk VIa et al.; Streptomyces aureofaciens 019(8), chlortetracycline producent was subjected to the effect of UV-light and nitrosoguanidine and after that its 121520 colonies have been analyzed by the methods of replicas and 57 mutants were isolated: sensitive to the effect of UV radiation--14; auxotrophs--30; antibiotic-inactive --13 . The induction frequency of mutations is within the limits of 0.016 to 0.067% . Auxotrophic mutants manifested genetic instability . Mutants with a block chlortetracyclin biosynthesis are stable. Minerva Cardioangiol, 1997 Mar, 45(3), 101 - 6 {Surgical therapy for prosthetic infections of the thoracic aorta . Conservative approach}; Spirito R et al.; The prosthetic graft infection of the thoracic aorta is a dreaded complication and it is associated with a high mortality rate . There is not substantial agreement in literature about how to manage a vascular graft infection, except for local anti-septic irrigation with a systemic antibiotic therapy . The main point of discussion is if it is mandatory to remove or not the infected thoracic aorta prosthesis: some authors prefer to eliminate all the thoracic aortic prostheses which may be infected, while others propose graft removal only when the sutures lines are involved . In this paper we report our experience on the conservative management of infected thoracic aorta prostheses using a local antiseptic irrigation, a perigraft debridement and leaving the original graft "in situ" when there is evidence of graft damage especially or involvement of the sutures lines . This approach has been performed in three patients: two had an infected aortic arch prosthesis, while one had a descending thoracic aorta prosthesis infection. Urologe A, 1997 Mar, 36(2), 157 - 61 {Treatment and follow-up of patients with squamous epithelial carcinoma of the penis}; Lummen G et al.; Since squamous cell carcinoma of the penis is rare, prospective trials do not exist . Therefore, new treatment strategies have to be developed . Based on our experience with the treatment of 22 patients with penile squamous cell carcinoma, we describe our therapeutic approaches . Ten patients with superficial disease (T1-2N0M0) were treated with partial penectomy . The 3-year survival rate amounted to 90% . In patients with extensive disease (T3-4 or N1-3) a partial or total penectomy was performed . After initial antibiotic therapy for 4 weeks, patients underwent inguinal lymph-node dissection and if the nodes were positive, additional pelvic lymph-node dissection . In patients with ulcerous inguinal lymph-node metastases surgical resection was performed, covering the wound with a musculocutaneous flap (tensor fascia lata flap n = 2; rectus abdominis flap n = 1) . The 3-year survival rate of patients with T1-2N1 tumours (n = 4) was 67% and with T3-4N1-3 (n = 8) 25% . Patients with distant metastases received inductive systemic chemotherapy with cisplatin, methotrexate and bleomycin . Objective responses occurred in 22% (1 CR, 1 PR) of 9 patients . These results suggest that immediate radical surgery with lymph-node dissection is the best treatment for squamous cell carcinoma of the penis. Minerva Urol Nefrol, 1997 Mar, 49(1), 45 - 9 {Emphysematous pyelonephritis . A clinical case successfully treated with percutaneous drainage}; Appignanesi P et al.; Emphysematous pyelonephritis is an unusual and serious infection, associated with the formation of gas by choliphormi bacteria . The authors present a case of monolateral emphysematous pyelonephritis in an obese and diabetic patient, put under observation and treated successfully through percutaneous drainage and antibiotic therapy. Zhonghua Yi Xue Za Zhi (Taipei), 1997 Mar, 59(3), 171 - 6 Clarithromycin in the combination therapy for the eradication of Helicobacter pylori in peptic ulcer disease; Lo WC et al.; BACKGROUND: Clarithromycin is a new macrolide antibiotic which is known to be highly effective in eradicating Helicobacter pylori (H . pylori) . In Chinese, the role of clarithromycin for H . pylori is still unclear . METHODS: Between January 1995 and February 1996, 75 patients with active H . pylori-positive duodenal ulcer were enrolled in this study . Three groups were randomized to have (1) 2 x 150 mg nizatidine twice daily, 2 x 250 mg amoxicillin four times daily, and 2 x 250 mg clarithromycin three times daily for two weeks (niz-amox-clar group, N = 25); or (2) 20 mg omeprazole twice daily plus 2 x 250 mg clarithromycin three times daily for two weeks (ome-clar group, N = 25); or (3) 300 mg bismuth subsalicylate four times daily, and 2 x 250 mg amoxicillin four times daily, 250 mg metronidazole four times daily for two weeks (triple therapy group, N = 25) . All the patients received H2 receptor antagonist (150 mg nizatidine or ranitidine, or 400 mg cimetidine, twice daily) for the consecutive six weeks . RESULTS: The eradication rate of H . pylori eight weeks after the entry of study was 80%(20/25) in the niz-amox-clar group, 76%(19/25) in the ome-clar group, 88%(22/25) in the triple therapy group (p < 0.05 among the three groups) . The ulcer healing rates eight weeks after the entry of study for the niz-amox-clar, the ome-amox, and the triple therapy groups were 84%(21/25), 80%(20/25), and 80%(20/25), respectively (p < 0.05 among the three groups) . The number of patients experiencing adverse effects in the niz-amox-clar group, the ome-clar group, and the triple therapy group were 10(40%), 7(28%), and 4(16%), respectively (p > 0.05 among the three groups) . CONCLUSIONS: Both nizatidine/amoxicillin/clarithromycin and omeprazole/clarithromycin regimens can achieve good eradication rates and may provide an effective alternative anti-H . pylori treatment in duodenal ulcer diseases. J Hand Surg {Am}, 1997 Mar, 22(2), 338 - 40 Flexor tenosynovitis in the hand caused by Mycobacterium malmoense: a case report; Gabl M et al.; This report analyzes a rare case of flexor tenosynovitis caused by Mycobacterium malmoense . A synovectomy was carried out on the index finger (no other finger was afflicted) of a 66-year-old farmer, followed by antibiotic therapy with ethambutol, rifampin, and clarithromycin . Because of strong side effects, the treatment with ethambutol and rifampicin had to be discontinued after 4 months . There was no recurrence after 14 months, and the patient's finger had a full range of motion. Changgeng Yi Xue Za Zhi, 1997 Mar, 20(1), 1 - 10 Management of infected total knee arthroplasty; Wang CJ; BACKGROUND: Deep wound infection after total knee arthroplasty is an infrequent but very serious complication . Treatment is difficult and challenging . Antibiotic therapy alone can not replace surgery in the management of infected total knee arthroplasty . METHODS: Fourteen infected total knee arthroplasties in 13 patients were treated by the author . Nine patients underwent two-stage reimplantation, one patient one-stage reimplantation, one patient arthroscopic debridement, and one patient knee fusion . Four knees in three patients were excluded because of less than 12 months follow-up . This study retrospectively analyzed the results of treatment in 10 infected total knee arthroplasties in 10 patients . RESULTS: All patients were followed up for 12 months or longer . The length of follow-up ranged from 12 months to 69 months with an average of 28 months . All infections were successfully controlled, and there was no recurrence of infection . However, only 67% of the patients showed satisfactory functional results . CONCLUSION: Based upon the results in this study, most of the infection after total knee arthroplasty could be successfully controlled by combined surgical treatment and intravenous antibiotic therapy . The result of two-stage reimplantation was more consistent and predictable . The functional result of infected total knee arthroplasty was less satisfactory as compared with that of the non-infected counterpart . Furthermore, the impact of infection or the longevity of total knee prosthesis could only be determined by long-term follow-up. Am J Crit Care, 1997 Mar, 6(2), 141 - 4 Control of infections caused by drug-resistant organisms in critical care; Hoppe B; The emergence of antibiotic-resistant pathogens has been an ongoing concern of infection-control and infectious disease practitioners . Infections caused by these organisms increase costs and may result in poorer outcomes for patients . Efforts to contain the problem of infections caused by drug-resistant organisms have two objectives: to optimize antibiotic use and to prevent transmission through effective infection-control practices. Z Naturforsch {C}, 1997 Mar-Apr, 52(3-4), 217 - 26 Isolation and analysis of moenomycin and its biosynthetic intermediates from Streptomyces ghanaensis (ATCC 14672) wildtype and selected mutants; Subramaniam-Niehaus B et al.; Streptomyces ghanaensis (ATCC 14672) produces the phosphoglycolipid antibiotic moenomycin consisting of several components . A solid phase extraction procedure was developed which allowed a rapid isolation of both moenomycin and its biosynthetic intermediates from culture filtrates . Semi-preparative high performance liquid chromatography followed by high performance liquid chromatography-mass spectrometry provided structural data on the different moenomycin components . In order to obtain initial information on the biosynthetic pathway, moenomycin non-producing mutants were isolated . They were shown to release intermediates with shorter lipid chains suggesting that the lipid chain synthesis probably takes place at a later stage of the moenomycin biosynthesis . Based on the biological activity and the analytical data, we assume that a modification and in particular a shorter lipid portion drastically influences the inhibitory activity of this antibiotic. Semin Neurol, 1997 Mar, 17(1), 63 - 8 Immunologic mechanisms in Lyme neuroborreliosis: the potential role of autoimmunity and molecular mimicry; Sigal LH; Most of the clinical manifestations of Lyme disease are due to the local presence of the causative agent, Borrelia burgdorferi, in the affected tissues . However, the precise means of tissue damage are not well understood and there is no proof that the organism, live or dead, is always present . An understanding of the complex interaction between the organism, the immune response elicited by the organism, and the host can explain manifestations of the disease and persistence of symptoms and signs after the antibiotic-induced death of the organism . It is possible that dead spirochetes, or fragments thereof may persist and act as a focus of ongoing inflammation . Different immunogenetic types may predispose to different immunologic responses, with distinct clinical outcomes . Vascular changes induced by the infection, either by local infection or the effects of cytokines on the vessel wall, may underlie tissue pathology . Finally, the immune response to B . burgdorferi may elicit the production of antibodies capable of recognizing and damaging or modifying normal host tissues . Only by establishing the mechanisms causing tissue damage in Lyme disease can rational therapeutic strategies be developed . Only by understanding these mechanisms can physicians and patients interpret clinical responses to therapy and accurately appreciate the clinical prognosis. J Laryngol Otol, 1997 Mar, 111(3), 274 - 6 Central nervous system complications of acute tonsillitis; Morgan N et al.; Acute tonsillitis is a common infection of early childhood which may even run a self-limiting course without antibiotic therapy in some cases . Complications are encountered infrequently and rarely assume a life-threatening propensity . Central nervous system involvement has not to our knowledge been described in association with tonsillitis without local abscess formation . We describe three cases in which acute tonsillitis/peritonsillitis was complicated by major central neurological sequelae . The neurological complications encountered in young previously healthy adults were: facial palsy and hemiplegia; superior sagittal sinus thrombosis with communicating hydrocephalus and papilloedema; Guillain-Barre syndrome and facial palsy . The pathogenesis and management is discussed . All patients made satisfactory recoveries, though with minor residual neurological disabilities. Orthop Nurs, 1997 Mar-Apr, 16(2), 31 - 46 Acute management of patients with hip fracture . A research literature review; Anders RL et al.; PURPOSE: To provide the orthopaedic nurse a summary of the significant research concerning the management of patients with a fractured hip . DESIGN: Meta-Analysis . SAMPLE: 135 articles reviewed for possible inclusion, 57 original research reports and publications are reported . METHODS: For the years 1985 to March 1996 Medline, MEDLARS, and CINAHL data bases were searched . Twenty-seven search terms were used, including hip fractured), orthopedic standards, and length of stay . MAIN RESEARCH CLASSIFICATIONS: Preoperative, Operative and Postoperative . Studies arranged by author, outcomes, focus, data source and year, sample, and findings . FINDINGS: Research reports were found concerning: preoperative care including the use of MRI, predictors of complications and transfusion needs, and impact of skin traction on pain; operative studies including spinal anesthesia and oxygen saturation rates, use of blankets to keep patient warm, prophylactic antibiotic use, and impact of delaying surgery; and postoperative reports including the incidence of DVT, nutritional status, cauterization, management protocols, morbidity and mortality risks, length of stay, functional status, and ambulation . CONCLUSION: The scientific merit of each study was not evaluated in depth . With some degree of comfort the review did find one study or several studies to support the findings presented . IMPLICATIONS FOR NURSING RESEARCH: Current research concerning the impact of pressure sores, incontinence, management of falls risk, and the impact the fear of falling on postinjury patients are just a few of the topics not adequately addressed. Br J Pharmacol, 1997 Mar, 120(5), 841 - 50 The effects of bradykinin on K+ currents in NG108-15 cells treated with U73122, a phospholipase C inhibitor, or neomycin; Hildebrandt JP et al.; 1 . Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration {Ca2+}i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM) . We studied the effect of the aminosteroid U73122 and the antibiotic neomycin, both putative blockers of phospholipase C (PLC), on these four bradykinin effects . 2 . Preincubation with 1 or 5 microM U73122 for 15 min partly suppressed Ins(1,4,5)P3 generation and the increase in {Ca2+}i induced by 1 microM bradykinin . U73122 10 microM caused total and irreversible inhibition . The inactive analogue U73343 was without effect . 3 . Resting levels of Ins(1,4,5)P3 were not affected . However, resting {Ca2+}i was increased by 10 microM U73122, but not by U73343 . Individual cells responded to 10 microM U73122 with a small increase in {Ca2+}i, followed in some cells by a large further rise . 4 . Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced the bradykinin-induced IK(Ca) to a fifth of its normal size . To suppress it totally, a 7-12 min pretreatment with 5 microM U73122 was required . Again, U73343 was without effect . 5 . U73122 and U73343 at concentrations of 5-10 microM irreversibly decreased the holding current (Ih) which at a holding potential of -30 or -20 mV mainly flows through open M channels . The decrease was often preceded by a transient increase . 6 . M current (IM) measured with 1 s pulses, was also decreased by 5-10 microM U73122 and U73343, but short applications of U73122 could cause a small increase . The bradykinin-induced inhibition of IM was not affected by U73122 . 7 . Preincubation with 1 or 3 mM neomycin for 15 min did not affect Ins(1,4,5)P3 generation and the increase in {Ca2+}i induced by bradykinin . Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin-induced IK(Ca) to a fifth of its normal size . 8 . The four main conclusions drawn from the results are: (a) U73122 suppresses bradykinin-induced PLC activation and IK(Ca), but not IM inhibition . (b) This indicates that the transient outward current IK(Ca), but not the decrease of IM in response to bradykinin, is mediated by PLC . (c) U73122 itself inhibits IM and mobilizes Ca2+ from intracellular stores . (d) Externally applied neomycin is not an effective inhibitor of PLC-mediated signalling pathways in NG108-15 cells. J Microencapsul, 1997 Mar-Apr, 14(2), 175 - 87 Biodegradable microparticles for sustained delivery of tetracycline to the periodontal pocket: formulatory and drug release studies; Esposito E et al.; This paper describes the production and characterization of biodegradable microparticles containing tetracycline, designed for periodontal disease therapy . The influence of production parameters on microparticle characteristics and antibiotic release modality was studied . Microparticles were made by using different preparation procedures and different polyesters, namely poly(L-lactide), {L-PLA} poly(DL-lactide), {DL-PLA} and poly(DL-lactide-co-glycolide) 50:50, {DL-PLG} . A double emulsion preparation method together with a concentrated salt solution as external phase gave the best results in terms of tetracycline incorporation efficacy . In vitro release experiments demonstrated that tetracycline is slowly and appropriately released from microparticles . Release kinetics were found to be influenced by the type of polymer utilized for microparticle production . In vitro experiments, simulating in vivo conditions were carried out for up to 30 days . Only DL-PLG microparticles showed significant changes in their morphology, whereas L-PLA and DL-PLA were found almost intact after the same period of time. Clin Biochem, 1997 Mar, 30(2), 135 - 42 Distribution of sirolimus in rat tissue; Napoli KL et al.; OBJECTIVES: To examine the distribution of sirolimus (SRL, rapamycin), an immunosuppressive macrolide antibiotic, in the tissues of adult male Wistar-Furth rats following continuous intravenous infusion (CIVI) and repeated daily peroral gavage (PO) . DESIGN AND METHODS: Animals received 14-day courses of SRL by either CIVI (0.04-0.4 mg/kg/day) or PO (0.4-1.6 mg/kg/day) administration . Samples of whole blood and homogenates of five solid organs (heart, kidney, liver, lung and spleen), and portions of intestinal, muscle and testicular tissues were prepared on day 13 of CIVI treatment or 24 hours after administration of the 14th PO dose . SRL concentrations were determined by high performance liquid chromatography with reference to calibration curves produced from SRL-spiked whole blood or tissue homogenates prepared from drug-free animals . RESULTS: Following PO but not CIVI administration, SRL concentrations in whole blood and all tissues increased linearly in relation to dose . SRL was extensively distributed among most tissues tested (tissue partitions coefficients of > 40 were observed in some cases) . Comparatively, SRL whole blood concentrations were low . The ratio between the SRL whole blood concentrations after PO versus after CIVI administration (at like doses of 0.4 mg/kg/day) was 0.04 . Therefore, we inferred that the oral bioavailability of SRL was low . CONCLUSIONS: The linear relationships between PO dose and SRL concentrations in whole blood and tissues may be attributed to the low oral bioavailability of SRL, which is indicated by the low levels of SRL observed in whole blood and tissues after PO administration . The nonlinear relationships between CIVI dose and SRL concentrations in whole blood and tissues may result because although whole blood depots may be saturated with SRL, the tissues continue to absorb SRL as the dose of SRL increases . Thus, because a high percentage of SRL is widely distributed into tissues stores, caution must be used when administering this drug in humans. Dis Colon Rectum, 1997 Mar, 40(3), 370 - 1 Bullous pemphigoid at colostomy site: report of a case; Vande Maele DM et al.; PURPOSE: Pemphigoid is a well-recognized cutaneous lesion, occurring rarely in peristomal skin . We report the diagnosis and successful treatment of localized pemphigoid lesions adjacent to a colostomy . METHODS: We review the chart, immunofluorescence study, treatment, and follow-up of a patient with bullous lesions at a colostomy site . RESULT: Pemphigoid of the pericolostomy skin was diagnosed by immunofluorescence study and successfully treated with antibiotic . CONCLUSION: Diagnosis of bullous pemphigoid should be considered in the differential diagnosis of a bullous lesion adjacent to a colostomy site . Diagnosis is easily made, and treatment is simple and efficacious. Am J Emerg Med, 1997 Mar, 15(2), 161 - 3 Simultaneous uvulitis and epiglottitis in adults; McNamara R et al.; The emergency physician must be aware of the varied ways in which epiglottitis can present . This report discusses two adult patients who presented with symptoms and signs indicative of uvulitis who were found to have associated epiglottitis . Neither patient reported respiratory difficulty but both experienced significant pain upon swallowing and were febrile with an enlarged, erythematous uvula . Management consisted of close observation and treatment with an intravenous antibiotic and corticosteroid . The emergency physician should consider the possibility of coexistent epiglottitis in the adult patient who presents with uvulitis. Clin Infect Dis, 1997 Mar, 24(3), 468 - 70 Infectious diseases consultation: impact on outcomes for hospitalized patients and results of a preliminary study; Classen DC et al.; In the absence of detailed and specific data on outcomes, specialists are thought to contribute excessively to the cost of care . Infectious diseases physicians are at further risk of heavy utilization of medical resources because their patients often are those with serious complications or expensive underlying diseases (e.g., AIDS) . By using readily available information in a sophisticated computer database, we examined the crude economic impact of an inpatient infectious diseases consultation and identified important matching variables for more refined analysis . The study was performed at LDS Hospital (Salt Lake City), a tertiary care facility with four full-time infectious diseases physicians . A total of 496 cases (patients who were seen by an infectious diseases consultant) were matched with 3,117 controls (patients who were not seen by an infectious diseases consultant) . Matching was performed on the basis of age, sex, exact discharge diagnosis-related group, minimum length of hospital stay equal to the interval from admission to consultation for cases, and measures of the severity of illness (nursing acuity score and the number of secondary diagnoses) . Cases had longer lengths of hospital stays, longer intensive care unit lengths of stays, and higher antibiotic costs than did matched controls, and if the consultation occurred in the last one-third of hospitalization, cases had shorter lengths of hospital stay and lower antibiotic costs than did controls. Presse Med, 1997 Mar, 26 Suppl 2, 27 - 9 {Asthma and Chlamydia pneumoniae . A future prospect for macrolides in general and roxithromycin in particular?}; Mayaud C; A LOGICAL HYPOTHESIS: Recent publications raise the question of an association between Chlamydia pneumoniae and asthma . There has been no formal proof justifying routine search for C.pneumoniae in patients with uncontrolled asthma nor for systematic treatment with an antibiotic . OPEN QUESTIONS: Can Chlamydia pneumoniae infection initiate or aggravate asthma? Are acute manifestations of asthma associated with an overly high frequency of recent C.pneumoniae infection? Is a past history of C.pneumoniae infection abnormally frequent in patients with chronic asthma? PERSPECTIVES: Rigorously controlled clinical trials evaluating the efficacy of antibiotics such as macrolides which are active against C.pneumoniae are warranted to further elucidate these questions. Patient Educ Couns, 1997 Mar, 30(3), 257 - 70 Design, development, and evaluation of visual aids for communicating prescription drug instructions to nonliterate patients in rural Cameroon; Ngoh LN et al.; In this study, culturally sensitive visual aids designed to help convey drug information to nonliterate female adults who had a prescription for a solid oral dosage form of antibiotic medications were developed and evaluated . The researchers conceptualized the educational messages while a local artist produced the visual aids . Seventy-eight female ambulatory patients were evaluated for comprehension and compliance with antibiotic prescription instructions . The study was conducted in three health centers in Cameroon, West Africa and followed a pre-test, post-test, and follow-up format for three groups: two experimental, and one control . All participants were randomly assigned to either experimental or control groups, 26 patients to each group . Subjects in the experimental groups received visual aids alone or visual aids plus an Advanced Organizer . A comparison of the three groups showed that subjects in the experimental groups scored significantly higher than the control group in both the comprehension and compliance measuresPIP: A study in rural Cameroon evaluated culturally sensitive visual aids designed to convey instructions for use of prescription antibiotics to illiterate women . The study, conducted in 3 health centers, used a pre-post test and follow-up format in 3 random groups (2 experimental and 1 control) of 26 patients each to test compliance with short-term prescriptions of antibiotics (ampicillin, sulfamethoxazole, trimethoprim, metronidazole, and tetracycline) . The introduction to this report reviews the literature on use of essential drugs by ambulatory patients and the problems of communicating directions for use to patients, especially illiterate patients in developing countries . Visual aids can use pictorial, graphic, or verbal symbols and must get the audience's attention, be culturally appropriate, and be relevant to the population to be served . The theoretical framework for the use of visual aids is found in Albert Bandura's Social Learning Theory of Identificatory Processes, which explains how to achieve behavior modification using modeling . This study involved use of a literacy test, visual aids, and an "advanced organizer." The advanced organizer (introductory information used to explain why the drug is needed) used farming as an analogy and described a body as a crop field, disease as weeds, and antibiotics as a farmer . Visual aids were developed through a conceptual and a design phase and were field tested . It was found that the experimental groups (1 with only visual aids, 1 with visual aids and the advanced organizer) scored significantly higher than the controls in measures of comprehension and compliance and that use of the advanced organizer improved scores significantly . It is concluded that, to be effective, visual aids must be population-specific but that their preparation and use contributes significantly to achieving desired results in patients . J Periodontol, 1997 Mar, 68(3), 299 - 305 Abscess formation around a hydroxyapatite-coated implant placed into the extraction socket with autogenous bone graft . A histological study using light microscopy, image processing, and confocal laser scanning microscopy; Takeshita F et al.; The purpose of this study was to evaluate the radiologic, histologic, and histometric findings for a retrieved hydroxyapatite (HA)-coated implant which had been placed into a fresh extraction socket with autogenous bone graft 3 months previously . A periapical radiography disclosed a vertical bone loss around the implant cervix . Examination of histologic section disclosed that granulation tissue including bone chips around the cervix, and newly-formed bone tissue around the grafted bone tissue on the HA coated surface . In the confocal laser scanning microscopic findings toluidine blue-negative bone tissue showed autofluorescence . Histometric analysis indicated that the average percent bone contact was 29.2% (ranged 26.4% to 34.1%) . Suspected reasons for failure were an early exposure of the barrier membrane, its early removal, the implant placement into an infected site, inadequate antibiotic premedication, and/or poor control of infections around teeth prior to implant surgery and around implants before and after placement of barrier membrane. Semin Respir Infect, 1997 Mar, 12(1), 7 - 11 Psittacosis; Gregory DW et al.; Pneumonia caused by Chlamydia psittaci likely occurs considerably more frequently than is suggested by the mere 100 to 200 cases reported annually to public health authorities . Parrots and other psittacine birds still are regarded as the major reservoir of the infectious agent and most recognized cases are associated with owning pet birds or working in a pet store . It was once thought that birds imported from abroad, often illegally, were a principal source, but many domestic breeder flocks of pet birds now have become infected . There is little that is distinctive in the clinical presentation of psittacosis . Therefore, a careful history of bird contact is often the first clue to the diagnosis . The diagnosis frequently is first considered in evaluating a patient whose pneumonia has not responded to therapy with a beta-lactam antibiotic . The diagnosis usually is established serologically . Tetracycline is the preferred therapy and is administered for three weeks to prevent relapses. Rinsho Ketsueki, 1997 Mar, 38(3), 228 - 30 {Positive seroconversion syphilis in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation}; Naohara T et al.; An acute lymphocytic leukemia patient underwent allogeneic bone marrow transplantation (BMT) from a sibling who was serologically positive for syphilis . After the donor was administered antibiotic therapy, the titration of treponema pallidum hemagglutination (TPHA) decreased from x1260 to x320 . Thereafter, the graft consisting of mononuclear cells was transplanted . TPHA of the recipient turned positive on day +63, but became negative 1.5 years after BMT . Although the cause of the seroconversion of TPHA seemed to be the contamination of treponema to the graft, the adoptive transfer could not be ruled out as an another possible cause. Masui, 1997 Mar, 46(3), 384 - 7 {Aspiration pneumonia during the endotracheal intubation on the occasion of bladder perforation by TUR}; Fukuhara H et al.; We report on two cases of aspiration pneumonia which developed during the endotracheal intubation after bladder perforation during TUR . The first case was a 79 y.o . male, who underwent TUR-P and lithotripsy under spinal and epidural anesthesia . The second case was a 69 y.o . male, who had undergone TUR-Bt under nitrous oxide-oxygen-enflurane anesthesia . General anesthesia was selected to perform an laparotomy when the diagnosis was made . They vomited a considerable amount of gastric content just after giving the drugs for induction . The chest X-rays revealed signs of aspiration pneumonia . These X-ray findings improved in a week using antibiotic therapy . Although TUR is performed as scheduled, vomiting may occur in the case of unexpected bladder perforation, which can cause aspiration pneumonia . In such emergency, we should insert a nasal tube before induction, press the cricoid (crush induction), or intubate with the patient awake. Anticancer Drugs, 1997 Mar, 8(3), 238 - 44 In vitro inhibition of endothelial cell growth by the antiangiogenic drug AGM-1470 (TNP-470) and the anti-endoglin antibody TEC-11; Maier JA et al.; Angiogenesis plays a key role in tumor growth, progression and metastasis . The modulation of angiogenesis represents a potentially useful target for novel forms of anticancer therapy . Two such modulators are AGM-1470 (TNP-470, angioinhibin), which is a synthetic analog of the antibiotic fumagallin, and the monoclonal antibody TEC-11 to endoglin . We investigated the mechanisms of action of these modulators on human microvascular and macrovascular endothelial cells and on the transformed endothelial cell line ECV-304 in vitro . The administration of AGM-1470 or TEC-11 resulted in a significant inhibition of cell proliferation in all cell types used; this effect was reversible upon removal of these compounds from the culture medium . Furthermore, biochemical and morphological analyses showed that neither AGM-1470 or TEC-11 induce apoptosis . Both AGM-1470 and TEC-11 inhibited the production of urokinase-type plasminogen activator (u-PA), an enzyme involved in the early steps of neovascularization . Finally, the incubation of endothelial cells with both AGM-1470 and TEC-11 did not produce an additive effect on growth cell inhibition, apoptosis or u-PA production . Since both AGM 1470 and TEC-11 inhibit crucial events such as endothelial cell growth and protease production, our results provide a basis for their therapeutic use as angiostatic molecules in cancer. J Pediatr Surg, 1997 Mar, 32(3), 486 - 8 Hepatic transplantation in children under 3 months of age: a single centre's experience; Bonatti H et al.; Liver transplantation in neonates represents a major medical and technical challenge particularly in babies weighing less than 5 kg . The authors report the experience of 10 liver transplants in 9 babies (6 boys and 3 girls), mean age, 6 weeks (range, 2 to 11); median weight, 3.7 kg (range, 2.4 to 5) . All had fulminant hepatic failure caused by neonatal haemochromatosis (n = 3), non-A non-B hepatitis (n = 3), total parenteral nutrition induced (n = 1), hepatitis B (n = 1), and hepatic haemangio-endothelioma (n = 1) . One child underwent retransplantation for hepatic artery thrombosis . Immunosuppression was by Cyclosporine A-based triple therapy in all cases . All received a reduced size graft consisting of left lobe (n = 1), left lateral segment (n = 6) and monosegment III (n = 3) . In nine cases the donor hepatic artery was anastomosed to an iliac artery conduit from the infrarenal aorta, and a Roux loop was used for bile duct reconstruction . Primary abdominal wound closure was possible in six patients, skin closure alone in one, and a silastic patch was used in three . Complications included infection (n = 5), bowel perforation (n = 2), diaphragmatic perforation (n = 2), bile leak (n = 1), hepatic artery thrombosis (n = 1), and portal vein thrombosis (n = 1) . None of the babies experienced acute rejection . Currently five of the nine recipients are alive with good graft function at a mean follow-up of 22 months (range, 5 to 58) . Of the four deaths, two were related to infection (one in combination with portal vein thrombosis), one to multiorgan failure and fluid overload, and one to early graft dysfunction and sepsis after undergoing retransplantation for hepatic artery thrombosis . From our experience liver transplantation offers a promising option for the treatment of severe liver disease in children less than 3 months old. J Comput Aided Mol Des, 1997 Mar, 11(2), 114 - 28 Structure-affinity relationships for the binding of actinomycin D to DNA; Gallego J et al.; Molecular models of the complexes between actinomycin D and 14 different DNA hexamers were built based on the X-ray crystal structure of the actinomycin-d(GAAGCTTC)2 complex . The DNA sequences included the canonical GpC binding step flanked by different base pairs, nonclassical binding sites such as GpG and GpT, and sites containing 2,6-diamino-purine . A good correlation was found between the intermolecular interaction energies calculated for the refined complexes and the relative preferences of actinomycin binding to standard and modified DNA . A detailed energy decomposition into van der Waals and electrostatic components for the interactions between the DNA base pairs and either the chromophore or the peptidic part of the antibiotic was performed for each complex . The resulting energy matrix was then subjected to principal component analysis, which showed that actinomycin D discriminates among different DNA sequences by an interplay of hydrogen bonding and stacking interactions . The structure-affinity relationships for this important antitumor drug are thus rationalized and may be used to advantage in design of novel sequence-specific DNA-binding agents. Int J STD AIDS, 1997 Mar, 8(3), 187 - 91 Demographic data on prostitutes from Bulgaria--a recruitment country for international (migratory) prostitutes; Tchoudomirova K et al.; The study was aimed at investigating the conditions and circumstances for the recruitment of prostitutes, as well as their reproductive history, working conditions, knowledge of and attitudes to sexually transmitted diseases (STDs), and use of prophylactic antibiotic therapy of these diseases . Two hundred prostitutes were investigated by in-depth interviews at STD clinics, private practices and hotels . Of the 200 prostitutes, 8 (4%) were less than 15 years old and 32 (16%) more than 25 years old . Most of the women came from rural villages . Half of them were gypsies . Most had a boyfriend (often the pimp) . One-quarter had been or were on their way abroad to prostitute . Half were migrating within Bulgaria to prostitute . They claimed a high rate of condom use with customers, but seldom with their pimps or boyfriends . About one-tenth used antibiotics prophylactically . They had knowledge of classical STDs and HIV/AIDS but only in exceptional cases had they heard about chlamydial and human papillomavirus infections . They often cohabited with a female friend also often practising prostitution . It was concluded that recruitment is often easy as the prostitute can earn more from only one contact with a customer than their parents earn from work in a month . Symptoms suggestive of STD were very common in the prostitutes, i.e . in 43% . Bulgaria is a recruitment area for international prostitutes. J Am Podiatr Med Assoc, 1997 Mar, 87(3), 125 - 30 Unusual presentation of calcaneal osteomyelitis . Twenty-five years after inoculation; Rogoff RS et al.; An unusual presentation of calcaneal osteomyelitis is described, where-by the infection remained undiagnosed for 25 years . The 36-year-old patient recently sought medical treatment for a reported ankle sprain, but the pain was recalcitrant to conservative care . Further investigation yielded a history significant for stepping on a chicken bone as a child, which entered the inferior lateral heel . Magnetic resonance imaging revealed what plain radiographs did not: a well demarcated lytic lesion in the body of the calcaneus . Intraoperative findings were consistent with an abscess of chronic osteomyelitis . The treatment included incision and drainage, antibiotic beads, and a tricortical bone graft. Pharmacotherapy, 1997 Mar-Apr, 17(2), 375 - 8 Phenytoin-oxacillin interactions in normal and uremic sera; Dasgupta A et al.; Displacement of phenytoin (90% bound to albumin) by other strongly albumin-bound drugs such as salicylate and valproic acid may result in an increase in pharmacologically active free concentrations . The antibiotic oxacillin is also strongly bound to albumin and is often administered to patients receiving phenytoin . Oxacillin at a concentration of 15 micrograms/ml caused no significant displacement of phenytoin in a serum pool prepared from patients receiving phenytoin . However, a significant increase in the free phenytoin concentration was seen at an oxacillin concentration of 50 micrograms/ml . We also prepared a serum pool from uremic patients and another from patients with hypoalbuminemia and supplemented both of them with phenytoin . Significant increases in the free phenytoin concentration occurred with both 15- and 50-microgram/ml concentrations of oxacillin . In one hypoalbuminemic patient receiving both phenytoin and intravenous high-dose oxacillin, the free phenytoin fraction was 22.5% before oxacillin therapy, 24.1% 12 hours after first dose of oxacillin, and 27.2% after 60 hours, indicating the possibility of in vivo displacement of phenytoin by oxacillin . We conclude that the phenytoin-oxacillin interaction is not significant at lower dosages of oxacillin usually prescribed for oral therapy . However, the interaction may be significant at high concentrations of oxacillin, especially in patients with hypoalbuminemia or uremia. Microbiology, 1997 Mar, 143 ( Pt 3), 875 - 83 Gene disruption and replacement in the rapamycin-producing Streptomyces hygroscopicus strain ATCC 29253; Lomovskaya N et al.; A system for gene disruption and replacement based on a streptomycete temperate phage vector was developed to introduce DNA in the rapamycin-producing Streptomyces hygroscopicus strain ATCC 29253 . This will be useful in attempts to produce, through genetic manipulation, novel forms of the therapeutically important immunosuppressive drug rapamycin . Recombinant phages were constructed from the phi C31 phage derivative KC515 (C+ attp) carrying a thiostrepton or viomycin resistance gene along with segments of the S . hygroscopicus chromosome . Each of the cloned segments also contained the aphll neomycin/kanamycin resistance gene to enable gene replacement by loss of the phage-derived DNA . Specific deletion of the entire polyketide synthase (PKS) believed to govern rapamycin biosynthesis resulted in the loss of rapamycin production . In contrast, disruption or deletion of a region predicted to encode four PKS open reading frames, or another region predicted to encode another PKS plus a cytochrome P450 hydroxylase and ferredoxin, had no effect on the production of rapamycin or nigericin, a polyether antibiotic also produced by S . hygroscopicus . Therefore, S . hygroscopicus may have the capacity to produce polyketides additional to rapamycin and nigericin. Microbiology, 1997 Mar, 143 ( Pt 3), 867 - 74 A novel fusidic acid resistance gene from Streptomyces lividans 66 encodes a highly specific esterase; von der Haar B et al.; Resistance to fusidic acid in Streptomyces lividans is due to secretion of an extracellular enzyme (FusH) that converts the steroid antibiotic into an inactive derivative . NH2-terminal and several internal amino acid sequences were prepared from the purified enzyme . Using one of the deduced oligonucleotides to probe a subgenomic DNA library, the fusH gene was cloned and sequenced . Sequence analysis located an ORF which, owing to the presence of two putative start codons, indicates a predicted protein with 520 or 509 amino acids . A signal peptide was identified by aligning the deduced amino acids with the N-terminal sequence determined for the mature enzyme . The C-terminal part of the deduced FusH contains a region of three tandemly repeated stretches of 50 amino acids, which is preceded and followed by amino acids showing high homology with the repeats . FusH was found to share a GDS motif with some deduced esterases . S . lividans transformants carrying fusH on a multicopy vector synthesized high levels of FusH . Purified FusH cleaved equally well an acetyl, a thioacetyl or a formyl group from the 16 beta-position of fusidic acid and its derivatives . However, a propionyl group at the 16 beta-position was attacked with difficulty and a 16 alpha-acetyl group was not hydrolysed at all . These data indicate that FusH is a highly specific esterase . The fusH gene is widely distributed among streptomycetes that modify fusidic acid to its inactive lactone derivative. J Vasc Interv Radiol, 1997 Mar-Apr, 8(2), 197 - 202 Replacement of accidentally removed tunneled venous catheters through existing subcutaneous tracts; Egglin TK et al.; PURPOSE: The authors describe their experience with reinsertion of accidentally removed tunneled venous catheters using existing subcutaneous tracts . MATERIALS AND METHODS: Replacement of 13 dislodged tunneled venous catheters was attempted a median of 12 hours (range, 3 hours to 5 days) after accidental removal . The catheters were needed for hemodialysis (n = 11), plasmapheresis (n = 1), or antibiotic therapy (n = 1) . The tunnel exit was probed in the same fashion as for a dislodged nephrostomy tube, and new catheters were reinserted once a guide wire was advanced into the central veins . The medical record was reviewed to determine materials used and occurrence of complications, if any . RESULTS: Replacement was successful in 12 of 13 patients . The remaining patient had a new catheter placed through a fresh puncture during the same visit . There were no infections associated with re-use of existing tunnels . In five patients, after probing the tract with a guide wire, new catheters were simply advanced into the desired position . Seven other successes required additional manipulations with use of dilators and peel-away sheaths . CONCLUSIONS: Tunneled catheters that "fall out" can be readily replace even when reinsertion is attempted up to 5 days later . This represents an important contribution that radiologists can offer in the management of venous access cases. Hear Res, 1997 Mar, 105(1-2), 191 - 201 Otoconial formation in the chick: changing patterns of tetracycline incorporation during embryonic development and after hatching; Kido T; The antibiotic tetracycline (TC) is incorporated into calcifying tissues and serves as a fluorescent marker for identifying calcifying sites in bone and otoconia . Fluorescent labeling was performed at different stages in chick embryos and newly hatched chicks . The stagewise changes in the intensity, location and time course of fluorescent labeling were assessed . TC/egg (1-2 mg) was injected into the yolk sacs of embryos on the 4th, 8th and 11th embryonic days (ED), and the embryos were then killed at specified times after injection . In newly hatched chicks, TC was injected daily intraperitoneally with 0.06 mg TC/g body weight for 7 days and the chicks were killed on the 8th day after hatching . Embryos injected on the 4th ED and killed on the 6th ED showed intense fluorescence in the saccular otoconial layer . All maculae from embryos killed after injection on the 4th ED showed uniformly intense fluorescence throughout the otoconial layer . By the 9th ED, otoconia in all three maculae (saccular, utricular, and lagenar) fluoresced . Maculae from embryos killed after injection on the 8th ED showed uniformly intense fluorescence throughout the otoconial layer or intense localized fluorescence mainly in the upper half of the otoconial layer . All maculae from embryos killed after injection on the 11th ED showed moderate to weak fluorescence primarily in the lower half of the otoconial layer . All maculae from posthatched chicks showed very weak fluorescence throughout the otoconial layer . Otoconia at the periphery of the maculae generally showed weak fluorescence in embryos that had been injected on the 4th and 8th ED, but not in embryos injected on the 11th ED . TC, which competes for calcium binding sites, may inhibit the formation of some otoconia . The formation of giant otoconia may reflect subtle changes in the crystallization microenvironment on these occasions . In brief, the results suggest that: (a) otoconial formation in the saccule precedes that of the utricle and lagena; (b) otoconial formation occurs during the early period (beginning the 6th ED); (c) otoconial formation is stratified, with those in the upper layer forming first and those in the lower layer forming last. Cancer Gene Ther, 1997 Mar-Apr, 4(2), 118 - 28 Purified herpes simplex thymidine kinase Retrovector particles . I . In vitro characterization, in situ transduction efficiency, and histopathological analyses of gene therapy-treated brain tumors; Kruse CA et al.; Replication-defective, highly purified retroviral vectors (Retrovector), at titers of 10(8) colony forming units/mL, were prepared that conferred either beta-galactosidase or herpes simplex thymidine kinase (HSV-TK) activity . 9L gliosarcoma cells, transduced efficiently in vitro, were highly sensitive to ganciclovir (GCV) . The mean frequency of in situ transduction, measured by flow cytometry of single-cell tumor suspensions isolated from rat brains, was 3.2 +/- 0.6%; similar assessments were made by staining of beta-galactosidase or by immunohistochemistry with anti-HSV-TK . In vitro HSV-TK-transduced and G418-selected 9L-TK gliosarcoma tumors treated with GCV were eradicated in approximately 53% of the animals (10/19) at day 26, however, 89% (17/19) histologically showed < 1% tumor volume . Histologic evaluation at day 26 of animals with established 9L tumors treated with intralesional injection of HSV-TK vector followed by GCV treatment showed that 29% (4/14) had no tumor; 50% (7/14) had < 1% tumor volume . Regression of tumors proceeded over the time since the complete rate was increased at day 60 . Neither HSV-TK vector particles nor GCV alone altered the histological profile of 9L tumors, but substantial numbers of CD4+ and CD8+ lymphocytes infiltrated the tumors of animals treated with both . In cured animals, the former tumor bed contained cell debris, immune cells, and fibroblasts and was without damage to adjacent brain . The efficacy of suicide gene therapy for rat gliosarcoma using highly purified virion vectors approaches that of packaging cell lines. Ophthalmic Surg Lasers, 1997 Mar, 28(3), 236 - 8 Gentamicin retinal toxicity after cataract surgery in an eye that underwent vitrectomy; Rosenbaum JD et al.; A cataract developed in a 23-year-old man 4 months after a vitrectomy to repair a traumatic retinal detachment . An uneventful phacoemulsification was performed, using antibiotic-fortified infusion solution . Afterward, a large area of atrophic retina, consistent with gentamicin toxicity, was observed in the macula . The patient remains stable with 20/200 best-corrected acuity . The authors suggest that because the vitreous had been removed, gentamicin was able to settle over the macula during the entire cataract procedure . Therefore, gentamicin should be used intracamerally with caution, especially in eyes in which vitrectomy has been performed. Drugs, 1997 Mar, 53(3), 453 - 82 Epirubicin . An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of breast cancer; Coukell AJ et al.; Epirubicin, an anthracycline antitumour antibiotic which is structurally related to doxorubicin, is among the most active single agents used in the management of patients with breast cancer . The drug may be administered alone or in combination with other agents both to patients with early breast cancer and to those with metastatic disease . There is a clear relationship between epirubicin dose and tumour response . Dose intensified regimens have produced improved response rates in patients with advanced breast cancer compared with standard dose therapy; however, improved overall survival has not yet been demonstrated . The combination of epirubicin with newer agents such as vinorelbine or paclitaxel shows considerable promise, as does the use of epirubicin in high dose regimens with peripheral blood progenitor cell support . The major adverse effects of epirubicin are acute dose-limiting haematological toxicity and cumulative dose-related cardiac toxicity . These effects are less severe after epirubicin administration than after equimolar doses of doxorubicin . Other major adverse effects of epirubicin administration include mucositis, nausea and vomiting, reversible alopecia and local cutaneous and vesicant reactions . In summary, epirubicin has an established role in the treatment of both early and advanced breast cancer . Incombination with other highly active agents or in dose intensified regimens administered with haemopoietic growth factor and/or peripheral blood progenitor cell support, epirubicin may play a significant role in emerging breast cancer treatment strategies. Acad Emerg Med, 1997 Mar, 4(3), 179 - 83 Prevalence of positive serology for acute Chlamydia pneumoniae infection in emergency department patients with persistent cough; Wright SW et al.; OBJECTIVE: To determine the prevalence of acute Chlamydia pneumoniae infection in ED patients presenting with a persistent cough . METHODS: This was a case series consisting of a convenience sample of 65 patients > or = 18 years of age who presented with a chief complaint of a cough lasting > or = 2 weeks . Patients were treated in the ED of an urban university hospital . Patients with immunosuppression, lung disease, pneumonia, or a cough lasting > or = 3 months were excluded . Acute and convalescent sera were assayed for antibody to C . pneumoniae . Subjects with C . pneumoniae antibody titers showing a fourfold rise in either immunoglobin M (IgM) or immunoglobin G (IgG) antibody, an IgM titer of > or = 16, or an IgG titer of > or = 512 were considered to have evidence of acute C . pneumoniae infection . RESULTS: Thirteen (20%; 95% CI, 11% to 32%) of the 65 subjects had serologic evidence of acute C . pneumoniae infection . Except for an increased rate of fever, clinical signs and symptoms and laboratory studies did not differentiate those who had C . pneumoniae from those who did not have the disease . Patients diagnosed as having Bordetella pertussis or Mycoplasma pneumoniae infection did not have serologic evidence of concurrent C . pneumoniae infection . CONCLUSIONS: C . pneumoniae infection appears to be associated with a persistent cough in ED patients . Clinicians should consider this organism when evaluating these patients . It is unclear whether antibiotic therapy is indicated for these patients . If antibiotics are used, a tetracycline or macrolide antibiotic would be most appropriate. J Clin Oncol, 1997 Mar, 15(3), 1163 - 70 Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients; Mitchell PL et al.; PURPOSE: Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use . Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority . This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective . PATIENTS AND METHODS: In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ({G-CSF} filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics . The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge . Patients could be randomized for up to four independent febrile episodes . A total of 186 episodes of febrile neutropenia were investigated . RESULTS: Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02) . G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge . The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04) . CONCLUSION: Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings. J Rheumatol, 1997 Mar, 24(3), 531 - 5 Misleading clinical aspects of hydroxyapatite deposits: a series of 15 cases; Claudepierre P et al.; OBJECTIVE: To study the characteristics of radiographs in diagnosis of hydroxyapatite deposits in sites other than the shoulders and hips . METHODS: We reviewed the records of patients hospitalized during the last 3 years whose final diagnosis was apatite deposits in sites other than the shoulders and hips . RESULTS: Ten women and 5 men were studied . The initial presentation mimicked septic arthritis or periarticular soft tissue abscess in 12 patients, corresponding to calcifications in the fingers (6), toes (2), wrists (2), elbow (1), and ankle (1) . One patient presented with a spontaneous coccygeal pain (precoccygeal deposit), one with a pseudotumoral process of the thigh (paradiaphyseal calcification), and one with acute cervical pain and dysphagia (longus coli muscle calcification) . Complete clinical healing was observed after an average of 4.9 days; 11 patients used nonsteroidal antiinflammatory drugs (NSAID), 2 used colchicine, one used oral steroids, and one had brief antibiotic therapy and used NSAID . CONCLUSION: Initial clinical aspects of apatite deposits in sites other than the shoulders and hips can often be misleading, especially by mimicking an infectious process . Careful analysis of immediate radiographic films can help to rapidly ascertain the diagnosis and thus avoid useless investigations or treatment. Mol Pharmacol, 1997 Mar, 51(3), 448 - 61 Copper-dependent oxidative and topoisomerase II-mediated DNA cleavage by a netropsin/4'-(9-acridinylamino)methanesulfon-m-anisidide combilexin; Henichart JP et al.; A conjugate molecule was synthesized by linking the DNA-intercalative antitumor drug 4'-(9-acridinylamino)methanesulfon-manisidide (mAMSA) via a 4-carboxamide side chain to a dipyrrolecarboxamide moiety structurally related to the minor groove-binding antibiotic netropsin . The molecule (netropsin/ mAMSA) behaves as a threading intercalator . Its netropsin-like tail becomes located in the minor groove of the double helix and serves to drive the hybrid molecule preferentially to AT-rich sites on various DNA fragments as revealed by DNase I footprinting . The hybrid retains the susceptibility to copper-dependent oxidation characteristic of the parent mAMSA moiety as well as its ability to generate oxygen radicals, which can mediate DNA damage, mainly at cytidine and guanosine nucleotides . It also retains the property of stimulating the formation of cleavable complexes with DNA in the presence of topoisomerase II, but its netropsin-like moiety confers little or no influence on the reaction with topoisomerase I . Although netropsin/mAMSA is less potent than mAMSA at producing cleavable complexes with topoisomerase II, it promotes the appearance of cleavage sites at much the same nucleotide sequences as does the parent compound . The dipyrrolecarboxamide tail is not silent, however, since it modifies the concentration-dependence of cleavable complex formation. Mol Pharmacol, 1997 Mar, 51(3), 422 - 30 Involvement of activator protein-1 and nuclear factor-kappaB transcription factors in the control of the DT-diaphorase expression induced by mitomycin C treatment; Yao KS et al.; The antitumor antibiotic mitomycin C is activated by several bioreductive enzymes, including DT-diaphorase . In HT29 cells, mitomycin C treatment results in the induction of DT-diaphorase as reflected in elevated steady state DT-diaphorase mRNA levels . An increase in the transcriptional rate was demonstrated by nuclear run-on assay . To investigate the molecular basis of the change in transcriptional activity caused by mitomycin C treatment, electrophoretic mobility shift assays were used to demonstrate the induction of nuclear factor binding to elements in the 5' flanking region of the DT-diaphorase gene . Treatment of HT29 cells with mitomycin C resulted in the dose-dependent induction of binding activity directed to the activator protein-1 (AP-1) binding element with a time course similar to that of mRNA elevation . Supershift assays using specific antibodies to Jun and Fos demonstrated the participation of both proteins in the binding activities generated . A binding activity for the nuclear factor-kappaB (NF-kappaB) site was induced with a similar time course . Both competitor and supershift experiments indicated that a heterodimer of the NF-kappaB proteins p50 and p65 was contained in the bound complex . To further investigate the functional consequences of such binding, we transfected HT29 cells with a plasmid containing 3 kb of the DT-diaphorase 5' region upstream of a reporter gene, chloramphenicol acetyltransferase . Treatment with mitomycin C resulted in a 5.5-fold increase in the expression of a chloramphenicol acetyltransferase construct containing 3 kb of DT-diaphorase promoter sequence . Using a series of deletion mutations based on this full-length construct, we found that two regions of the DT-diaphorase promoter region, positions -346 to -588 (containing the AP-1 element) and positions -785 to -890 (containing the NF-kappaB element) are required for the full expression of the mitomycin C response . The specific involvement of these binding elements was confirmed using mutational analysis . The results demonstrate that mutation of either element alone or of both diminishes the response, indicating an additive interaction between the elements at a minimum . However, inducibility characterizes a promoter fragment as small as 78 base-pairs from the transcription start site . Treatment of cells with mitomycin C induced binding to a 38-base-pair region (-40 to -78) devoid of known transcription factor binding elements . These data suggest that mitomycin C induces the overexpression of DT-diaphorase through a mechanism involving both the AP-1 and NF-kappaB response elements and that inducibility depends on a novel factor binding element. Antimicrob Agents Chemother, 1997 Mar, 41(3), 661 - 4 Development of a high-performance liquid chromatographic assay for G418 sulfate (Geneticin); Bethune C et al.; We have developed a chromatographic assay with high sensitivity and specificity to quantify G418 sulfate (Geneticin), an antibiotic used routinely in molecular genetics experiments for selecting eukaryotic transformants . With this method, G418 in tissues and plasma samples can be quantitated without the confounding factors often associated with biological assays . After removal of proteins in homogenized tissue or plasma samples with methanol (2:1, vol/vol), the amino group of G418 was derivatized with 1-fluoro-2,4-dinitrobenzene (DNFB) to form the UV-visible G418-DNFB product . The DNFB-derivatized G418 was separated on a reversed-phase C18 column with an acetonitrile and water gradient as the mobile phase . Under these assay conditions, the detection limit for G418 sulfate in buffer, plasma, and tissues was recorded at 78 ng/ml and the linearity was recorded for concentrations up to 100 micrograms/ml . The data obtained from this analysis indicate that this assay can be used for the quantitative determination of G418 sulfate in plasma and tissue samples. J Bacteriol, 1997 Mar, 179(5), 1796 - 804 Characterization of a mitomycin-binding drug resistance mechanism from the producing organism, Streptomyces lavendulae; Sheldon PJ et al.; In an effort to characterize the diversity of mechanisms involved in cellular self-protection against the antitumor antibiotic mitomycin C (MC), DNA fragments from the producing organism (Streptomyces lavendulae) were introduced into Streptomyces lividans and transformants were selected for resistance to the drug . Subcloning of a 4.0-kb BclI fragment revealed the presence of an MC resistance determinant, mrd . Nucleotide sequence analysis identified an open reading frame consisting of 130 amino acids with a predicted molecular weight of 14,364 . Transcriptional analysis revealed that mrd is expressed constitutively, with increased transcription in the presence of MC . Expression of mrd in Escherichia coli resulted in the synthesis of a soluble protein with an Mr of 14,400 that conferred high-level cellular resistance to MC and a series of structurally related natural products . Purified MRD was shown to function as a drug-binding protein that provides protection against cross-linking of DNA by preventing reductive activation of MC. J Infect Dis, 1997 Mar, 175(3), 720 - 2 A population-based seroepidemiologic study of human granulocytic ehrlichiosis and Lyme borreliosis on the west coast of Sweden; Dumler JS et al.; Ehrlichioses are emerging infections in the United States . Human granulocytic ehrlichiosis (HGE) and Lyme borreliosis (LB) are acquired after Ixodes ricinus-complex tick bites . An ongoing seroepidemiologic study of the 185 of the 356 permanent residents of the Koster Islands in Sweden was expanded to include ehrlichioses . Ehrlichial antibodies were measured by IFA using Ehrlichia equi and Ehrlichia chaffeensis . Borrelia burgdorferi IgG ELISA-seropositive subjects were confirmed by Western blot . E . equi and E . chaffeensis antibodies (titer > or = 80) were found in 21 (11.4%) and 2 (1.1%) of 185 samples, respectively . Antibodies to B . burgdorferi were found in 25 (13.5%) of 185 . Six persons were seropositive for both HGE and LB . Among data from questionnaires, clinical symptoms, antibiotic treatments, or tick bites were not more frequent in E . equi- or B . burgdorferi-seropositive than -seronegative persons . The seroprevalence of HGE was similar to that of Lyme borreliosis . Prospective studies of European HGE are needed. Gastroenterology, 1997 Mar, 112(3), 991 - 4 Low albumin gradient ascites complicating severe pseudomembranous colitis; Zuckerman E et al.; Pseudomembranous colitis (PMC) is a frequently severe, sometimes fatal iatrogenic disease that is antibiotic-associated in almost all cases . The most common clinical features of PMC include abdominal pain, watery diarrhea, fever, leukocytosis, hypoalbuminemia, and hypovolemia . Ascites, not considered a well-known feature of PMC, is fairly common, based on a review of the English language literature but has not been characterized fully . This case report describes 5 patients with PMC who presented with low serum-ascites albumin gradient (SAAG) and neutrocytic ascites, without evidence of infectious, malignant, or inflammatory peritoneal disease, which has not been reported previously . In 1 patient, massive low SAAG ascites was the presenting manifestation of PMC, a feature also not reported previously . Three of the 5 (60%) patients had acquired immunodeficiency syndrome . The characteristics of the fluid specimens in these 5 patients and the possible pathogenetic mechanisms are proposed . The findings suggest that PMC should be included in the differential diagnosis of low SAAG ascites, especially in patients with acquired immunodeficiency syndrome. Chem Phys Lipids, 1997 Feb 28, 85(2), 145 - 55 The effect of aggregation state of amphotericin-B on its interactions with cholesterol- or ergosterol-containing phosphatidylcholine monolayers; Barwicz J et al.; Amphotericin B (AmB) is the most effective antibiotic used in the treatment of systemic fungal infections . It is generally thought that the activity of this drug results from its interaction with ergosterol, the main sterol of fungi membranes . However, AmB also interacts with cholesterol, the major sterol of mammal membranes, thus limiting the usefulness of this drug due to its relatively high toxicity . The aim of the present work is to study the molecular basis of the interactions of AmB with these sterols contained in a DOPC film by using the monolayer technique . Two different concentrations of the sterols in the film (13 and 30%) at an initial surface pressure of 30 mN/m were studied, which correspond to conditions found in various biological membranes . Four concentrations of AmB in the subphase, ranging from a molecularly dispersed to a highly aggregated state of the drug were studied . Our results show that the monomeric form of AmB interacts with the ergosterol containing film solely . On the other hand, when AmB is dispersed as a pre-micellar or as a highly aggregated state in the subphase, a very significant selectivity of its interactions between the two sterols is observed which is shown in our experimental results by a difference of 8 mN/m in the surface pressure when AmB interacts with ergosterol as compared to cholesterol . We show that the activity of AmB is most likely related to the micellar form of the antibiotic . In addition, we observe that upon increasing the amount of ergosterol in the film, the insertion of AmB is largely promoted, results that are discussed in terms of the molecular organization of the sterols within the monolayer film . We show that these results provide a better understanding of the action of AmB (activity/toxicity) at the membrane level. J Med Chem, 1997 Feb 28, 40(5), 771 - 84 Synthesis, antiproliferative and antiviral activity of imidazo{4,5-d}isothiazole nucleosides as 5:5 fused analogs of nebularine and 6-methylpurine ribonucleoside; Swayze EE et al.; A series of imidazo{4,5-d}isothiazole nucleosides related to the antibiotic nebularine and the highly cytotoxic 6-methyl-9-beta-D-ribofuranosylpurine have been synthesized from the corresponding heterocycles . The sodium salt glycosylation of the imidazo{4,5-d}isothiazoles proceeded smoothly, giving mixtures of N-4 and N-6 regioisomers in generally good yields . The protected derivatives were deblocked using standard conditions to afford the desired imidazo{4,5-d}-isothiazole nucleosides, usually as crystalline solids . None of the new nucleosides or heterocycles displayed selective activity against human cytomegalovirus (HCMV) or herpes simplex virus type 1 (HSV-1) . The N-6 glycosylated imidazo{4,5-d}isothiazoles were completely inactive up to the highest concentration tested . The N-6 glycosylated imidazo{4,5-d}isothiazoles also were inactive in antiproliferative and cytotoxicity assays, except for 3-methyl-6-beta-D-ribofuranosylimidazo{4,5-d}isothiazole (15a) and 5-(benzylthio)-6-(2-deoxy-beta-D-ribofuranosyl)imidazo{4,5-d}isothiaz ole (5e), which showed moderate inhibition of L1210 cell growth . However, the heterocycles and several of the N-4 glycosylated derivatives were toxic to HFF, KB and L1210 cells; compounds with 5-benzylthio substituents were the most cytotoxic agents in this series. Biochemistry, 1997 Feb 25, 36(8), 2291 - 9 Differential interactions of the Mg2+ complexes of chromomycin A3 and mithramycin with poly(dG-dC) x poly(dC-dG) and poly(dG) x poly(dC); Majee S et al.; The interaction of the two anticancer antibiotics, chromomycin A3 and mithramycin, with the polynucleotides poly(dG-dC) x poly(dC-dG), representative of B-DNA, and poly(dG) x poly(dC), representative of A-DNA, in the presence of Mg2+ is studied by spectroscopic techniques such as absorbance, fluorescence, and dircular dichroism (CD) . The studies were done with both drug x Mg2+ complexes, I and II, having 1:1 and 2:1 stoichiometries with respect to drug and Mg2+, respectively {Aich, P., Sen, R., & Dasgupta, D . (1992) Biochemistry 31, 2988-2997} . The objective of the present work is 2-fold . First, an attempt is made to understand the structural basis of the ligand-DNA interaction, particularly the role of DNA backbone conformation with its groove size and the accessibility of the 2-amino group in the minor groove of guanosine . Second, the role of the antibiotic saccharide moieties in the association with DNA was studied . For this purpose, the spectroscopic characterization of the binding was done followed by the evaluation of binding parameters and associated thermodynamics . Analysis of the observed thermodynamics for the ligand-DNA interactions in terms of the different structures of the polynucleotides was done . The salient results are as follows . Complex I does not discriminate significantly among the A- and B-forms of DNA when it binds to them in an entropy-driven process . On the other hand, complex II for both drugs recognizes B- and A-forms of DNA in different ways . This observation implies that the sequence specificity shown by this complex is a sequel to the difference in the parameters such as groove size and accessibility of the guanosine amino group . Another important finding is that binding with the same polynucleotide is not comparable for the complex II of the two drugs . It emphasizes the involvement of the sugar moieties, when the drug x Mg2+ complex binds to DNA . The presence of an acetoxy group in the sugars of chromomycin A3 imparts some distinctive specific features of the association of the chromomycin dimer x Mg2+ complex with DNA . Finally, the results are compared with those available from NMR studies of different drug-oligonucleotide complexes under conditions where complex II is the ligand. J Chromatogr A, 1997 Feb 21, 762(1-2), 327 - 33 High-performance liquid chromatographic separation of beta-methyl ADC-13 enolphosphate diphenyl ester and its alpha-methyl diastereomer; Wang T; The development of a high-performance liquid chromatographic (HPLC) separation of beta-methyl ADC-13 enolphosphate diphenyl ester, an intermediate compound in the synthesis of a carbapenem antibiotic drug candidate, and its alpha-methyl diastereomer is reported . The method development involved separation on different columns in both normal- and reversed-phase modes . The use of normal-phase mode resulted in the desired elution order of the two diastereomers . The influence of different polar modifiers and their concentrations on resolution, capacity factor and separation factor was investigated . Different stationary phases were compared for their efficiency and resolution . The optimized separation was applied to the determination of the minor diastereomer in the bulk intermediate, and 0.1% minor diastereomer was detectable. Proc Natl Acad Sci U S A, 1997 Feb 18, 94(4), 1160 - 5 Novel pyridinium surfactants for efficient, nontoxic in vitro gene delivery; van der Woude I et al.; Novel, double-chained pyridinium compounds have been developed that display highly efficient DNA transfection properties . The transfection efficiency of several of these compounds is enhanced by an order of magnitude, when compared with the transfection efficiency accomplished with the widely used cationic lipid system, lipofectin . Most importantly, the pyridinium compounds were found to be essentially nontoxic toward cells . Using various reporter genes, such as beta-galactosidase and pNEO (a gene construct that renders cells resistent to antibiotic derivatives of neomycin like G418), we demonstrate that the enhanced efficiency relates to the fact that a relative higher number of cells in the population is transfected (approximately 50% in the case of COS cells) by the pyridinium derivatives, whereas the delivery of DNA per cell is also enhanced . Furthermore, application of the pyridinium derivatives shows little cellular preference in their ability to transfect cells . By systematically modifying the structure of the pyridinium amphiphile, i.e., by changing either the headgroup structure or the alkyl chains, some insight was obtained that may lead to unraveling the mechanism of amphiphile-mediated transfection, and thus to protocols that further optimize the carrier properties of the amphiphile . Our results reveal that unsaturated alkyl chains enhance the transfection properties of the pyridinium-based amphiphiles . Preliminary experiments suggest that the structure-dependent improvement of transfection efficiency, when comparing pyridinium derivatives with lipofectin, likely relates to the mechanism of delivery rather than the packaging of the amphiphile/DNA complex. J Clin Invest, 1997 Feb 15, 99(4), 608 - 17 Prevention of bleomycin-induced pulmonary fibrosis after adenovirus-mediated transfer of the bacterial bleomycin resistance gene; Tran PL et al.; A serious limitation in the use of the DNA-cleaving, antitumoral-antibiotic, bleomycin during chemotherapy is pulmonary toxicity . Lung injury induced by bleomycin is characterized by an increased deposition of interstitial extracellular matrix proteins in the alveolar wall that compromises respiratory function . Several drugs have been tested in animal models to prevent the pulmonary toxicity of bleomycin, but have not led to a useful clinical treatment because of their adverse effects on other tissues . We have shown that transgenic mice expressing Streptoalloteichus hindustanus (Sh) ble bleomycin resistance protein in pulmonary epithelial cells in the lungs are protected against bleomycin-induced toxicity in lungs . In the present study, we used intranasal administration by adenovirus-mediated gene transfer of the bleomycin resistance Sh ble gene to mouse lung for prevention of bleomycin-induced pulmonary fibrosis . We constructed recombinant adenoviruses Ad.CMVble and Ad.RSVble harboring the bleomycin resistance Sh ble gene under the control of the cytomegalovirus early promoter and the Rous sarcoma virus early promoter, respectively . Transgene expression was detected in epithelia of conducting airways and alveolar septa by immunostaining with a rabbit polyclonal antibody directed against the bleomycin resistance protein and persisted for the duration of drug treatment; i.e., up to 17 d . No toxic effect was seen in adenovirus-treated mice . Pretreatment of mice with Ad.CMVble or Ad.RSVble completely prevented collagen deposition 42-133 d after bleomycin treatment, as measured by lung OH-proline content . Histologic studies indicated that there was little or no lung injury in the adenovirus/bleomycin-treated mice compared with the bleomycin-treated mice . These observations may lead to new approaches for the prevention of bleomycin-induced pulmonary fibrosis. Toxicol Lett, 1997 Feb 7, 90(2-3), 217 - 21 Poly-l-aspartic acid protects cultured human proximal tubule cells against aminoglycoside-induced electrophysiological alterations; Todd JH et al.; Cultured human proximal tubule cell monolayers maintained on permeable supports were treated simultaneously with the aminoglycoside antibiotic, gentamicin, and poly-L-aspartic acid (PAA), an inhibitor of aminoglycoside nephrotoxicity . Following 4 days of exposure, cell monolayers were placed into Ussing chambers to allow monitoring of transepithelial electrical properties . For each of the three cell isolates examined, aminoglycoside-induced alterations in electrogenic transport, reflected by changes in short-circuit current (Isc), as well as alterations in paracellular properties, indicated by changes in transepithelial electrical resistance (RT), were diminished in the presence of PAA . Alterations resulting from selective basolateral exposure to gentamicin were unchanged in the case of apically applied PAA and attenuated only when PAA acid was added basolaterally . This is the first demonstration of PAA inhibition of aminoglycoside-induced cellular alterations involving human cells. Am J Ophthalmol, 1997 Feb, 123(2), 252 - 4 Primary varicella-zoster keratitis: diagnosis by polymerase chain reaction; Power WJ et al.; PURPOSE: To report the value of polymerase chain reaction in the diagnosis of a worsening corneal ulcer . METHODS: A 6-year-old boy underwent an emergent penetrating keratoplasty for a corneal ulcer that continued to worsen despite intensive antibiotic therapy . RESULTS: Examination of the corneal specimen by polymerase chain reaction was positive for varicella-zoster virus but negative for herpes simplex . Based on polymerase chain reaction studies, we diagnosed primary varicella-zoster keratitis with corneal perforation . Electron microscopy showed herpetic virus particles in the cornea . CONCLUSIONS: Polymerase chain reaction analysis of corneal buttons at the time of penetrating keratoplasty may benefit patients with undiagnosed recalcitrant corneal ulcers. Arch Mal Coeur Vaiss, 1997 Feb, 90(2), 285 - 9 {Giant aneurysm of the interventricular septum . Value of imaging techniques}; Revel F et al.; A pseudosubaortic left ventricular aneurysm was discovered in a 32 year old African presenting with pyrexia after a long history of chest pains and dyspnea . Echographic and radiological techniques showed a large pulsatile mediastinal mass and the patient was referred for aneurysmorrhaphy . The actiology of this pseudo-aneurysm is discussed with reference to data in the literature . Infection is the first cause to be excluded in view of the pyrexia truncated by "blind" anti-inflammatory and antibiotic therapy . The hypothesis of an interventricular septal abscess secondary to septicaemia with secondary rupture into the pericardium is discussed . Precessive endocarditis with an aseptic abscess is unlikely because of the minimal aortic valve lesions, the absence of vegetations and the very long clinical evolution . Finally, idiopathic pseudo-aneurysms in sub-Saharian Africans, due to a congenital defect of the fibrous aortico-mitral and subannular zones must be considered . The risk of complications of these pseudo-aneurysms justifies surgical intervention on the accurate anatomical description of the lesions provide by transthoracic and transoesophageal echocardiography and magnetic resonance imaging. Genetika, 1997 Feb, 33(2), 284 - 6 {Role of the rpoS gene in the regulation of expression of plasmid genes determining the synthesis of C51 microcin}; Fomenko DE et al.; In cells mutant for the rpoS gene coding the sigma s subunit of RNA polymerase, synthesis of antibiotic microcin C51, which is produced by Escherichia coli, is absent or extremely reduced . In experiments with a cloned promoter of the microcin operon, the sigma s subunit was shown to participate in regulation of transcription of plasmid genes that determine microcin synthesis. Allerg Immunol (Paris), 1997 Feb, 29(2), 36 - 8 {Clinico-immunological study of 16 cases of benzoate intolerance in children}; Petrus M et al.; The authors report a sery of 16 cases of intolerance to the benzoates in children . Sixteen children (9 boys and 7 girls) were directed to the Hospital of Tarbes from June 1995 to July 1995, for recurring urticaria (7/16) combined with asthma (1/16), atopic eczema (2/16), dermorespiratory syndrome (2/16) and asthma (1/16) . All were subject to an immunological examination comprising alimentation inquiry, prick test, IgE determination, RAST, oral provocation test to benzoates, which establishes the diagnosis, whose confirmation is certified by the benefit of the food eviction . To conclusion, the authors underline several points: the presumable underestimation of the intolerance, the often mentioned atopic familial context, the observed pathology (urticaria, asthma, eczema), the importance of the provocation test . Finally, besides food such as grey shrimps, sodas and antibiotic syrups, one finds benzoates in the antiallergic syrups initially prescribed as a preventive measure. Unfallchirurg, 1997 Feb, 100(2), 111 - 8 {Seidel humerus intramedullary nailing . Clinical results of 100 surgeries}; Kelsch G et al.; Between 01.01.88 and 30.07.94 we treated 81 traumatic and 19 pathologic humeral shaft fractures with the Seidel humeral locking nail (HLN) . The majority of the 100 patients (60 women, 40 men) were older than 60 years of age . The dominant fracture type according to AO was type A . Operative stabilization was considered indicate because of fracture distraction during functional bracing in most cases . In general, patients choose surgical intervention in preference to conservative management . Radiological consolidation was observed within 10 weeks . In 48 cases sonography revealed motor disturbances between the gliding sheath of the rotator cuff, but there was no correlation between this and the shoulder mobility . In 7 cases an additional fracture was created during introduction of the nail . This complication can be avoided by using the right technique . There were no cases of non-union or radial nerve lesion . There were 2 patients who developed an infection, which disappeared after removal of the nail and introduction of antibiotic-loaded beads . Functional results were recorded in 63 patients: 53 patients (84%) had an excellent or satisfactory result (NEER score > 80) . Among the others, problems at the site of nail insertion predominated . In our view, the Seidel humeral locking nail is an implant that provides exercise stability without intraoperative positioning problems or risk of injury to nerves or vessels . Nevertheless, this method needs a skilled surgeon with special training to handle typical technical nailing problems. Br J Neurosurg, 1997 Feb, 11(1), 75 - 7 Spontaneous drainage of an infratentorial extradural empyema: case report; Nathoo N et al.; We describe a 21-year-old male who presented with spontaneous drainage of an infratentorial extradural empyema secondary to mastoiditis . Following eradication of the primary source, the patient was commenced on high dose intravenous antibiotics . Serial computed tomography (CT) revealed complete resolution of the pus collection . Antibiotic therapy was successful and no neurosurgical intervention was necessary. Genitourin Med, 1997 Feb, 73(1), 59 - 62 Non-cultural detection of rectal and pharyngeal gonorrhoea by the Gen-Probe PACE 2 assay; Young H et al.; OBJECTIVE: To assess the sensitivity and specificity of the Gen-Probe PACE 2 assay, which uses a chemiluminescent labelled single-stranded DNA probe to detect gonococcal ribosomal RNA (rRNA), for the non-cultural detection of rectal and pharyngeal gonorrhoea in homosexual men . SUBJECTS: 161 homosexual men attending the Department of Genitourinary Medicine, Edinburgh Royal Infirmary during the latter half of 1995 and the first quarter of 1996 . METHODS: Duplicate rectal and pharyngeal swabs were collected for culture on modified New York City (MNYC) medium and detection of gonococcal nucleic acid by the Gen-Probe assay . Repeatedly reactive Gen-Probe specimens from culture negative patients were also tested by the Gen-Probe competition assay (PCA) . RESULTS: Of the 161 patients, 23 (14.3%) gave a positive culture at one or both sites (rectum 10, throat 8, rectum and throat 5) compared with 28 (16.7%) who gave a positive Gen-Probe result at one or both sites (rectum 9, throat 11, rectum and throat 8) . After resolution of discrepant results by PCA the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Gen-Probe was 94.1%, 100%, 100% and 99.3% for rectal specimens while the corresponding values for pharyngeal specimens were 86.4%, 100%, 100%, and 97.9% . The sensitivity and NPV of rectal culture were 88.2% and 98.6% while the corresponding values for pharyngeal culture were 59% and 93.9% . Gen-Probe was significantly more sensitive than throat culture (p < 0.05) but not rectal culture (p > 0.2) . The average Relative Light Units (RLU) value for the cut-off was 386 (range 351-450) while the average for a positive result was 20306 (range 403-110104): this was, however, significantly higher (p = 0.019) in rectal specimens 31325 (range 1705-110104) than in throat specimens 10447 (range 403-15633) . CONCLUSIONS: Gen-Probe PACE 2 assay is a sensitive and specific method for the detection of rectal and pharyngeal gonorrhoea . As the Gen-Probe assay may detect nucleic acid from non viable gonococci the clinical significance of a probe positive culture negative specimen from a patient without culture evidence of gonorrhoea at another site is uncertain and requires further consideration . Nevertheless a positive result does indicate exposure to infection and could be important in ensuring appropriate partner notification action . If non-cultural methods are used to screen for gonococcal infection cultures should be obtained from patients with positive results in order that the antibiotic susceptibility and molecular epidemiology of the gonococcal population can be monitored. Clin Infect Dis, 1997 Feb, 24 Suppl 2, S181 - 3 Penetration of meropenem in plasma and abdominal tissues from patients undergoing intraabdominal surgery; Condon RE et al.; We assessed the penetration of a new carbapenem antibiotic, meropenem, into abdominal tissues . A single 1,000-mg intravenous dose was administered to 66 patients undergoing elective intraabdominal surgery . Plasma, body fluid (peritoneal fluid and bile), and tissue samples (colon, gallbladder, omentum, stomach, fascia, muscle, and skin) were taken at various times up to 8 hours after administration of the dose . Meropenem concentrations were determined by means of validated bioassay techniques . Peak meropenem concentrations in most tissue specimens and one body fluid occurred within approximately 1 hour; the exceptions were bile and muscle specimens, in which peak concentrations were present in approximately 2 to approximately 4 hours . The bile concentration increased with time, thus indicating active excretion of drug into bile . Only one adverse event (mild nausea) was attributable to meropenem . Our results show that meropenem achieves adequate tissue concentrations for the treatment of intraabdominal infections due to susceptible bac