Hist Sci Med, 1994, 28(3), 239 - 48 Not Available Gonzales J. The discovery of streptomycin by Waksman in 1943 marked the beginning of true chemotherapy in all forms of tuberculosis . The possibility to reverse the lethal course of tuberculous meningitis in children constituted a hope verged on enthusiasm . But after encouraged results, skepticism arose: cases of resistance of BK to streptomycin were reported and other observations noted severe sequelae when administration had begun too late . Successes due to drug were often weakened by side effects like cochlear and vestibular deficiencies . All those reservations came in addition to the great price of streptomycin, difficulties of its supply and doubts upon long term prognosis for cared patients . Finally streptomycin won . In the following years, new drugs more and more efficient against tuberculosis were used, instead of streptomycin which some enthusiastic people had nevertheless thought only able to eradicate the "white plague" . Today, morbidity and mortality from tuberculosis remain dramatic, partly accelerated by the AIDS epidemic and increased by high frequency of cases with BK resistance to all drugs .. . except streptomycin . What a long story, full of hopes, for this antibiotic which, during the first clinical trials, saved from certain death .. . a child became the author of the present paper! Bone Marrow Transplant, 2001 Sep, 28(6), 619 - 21 Ulcerative colitis after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma; Koike K et al.; A 54-year-old woman with peripheral T cell lymphoma in second complete remission (CR) received an autologous peripheral blood stem cell transplant (PBSCT) . Antibiotic-resistant bloody diarrhea, and fever developed 110 days after transplant . Blood and stool cultures were negative . Skin rash was not observed . Barium enema and colonoscopy showed typical features of pancolonic-type ulcerative colitis (UC) . Endoscopic biopsies confirmed the diagnosis of UC . Mesalazine and immunosuppressive therapy improved symptoms dramatically . We detected serum antibodies against synthetic tropomyosin (TM) peptide when UC was diagnosed . We postulate that autoimmunity including autoreactive anti-TM antibodies may be involved in the pathogenesis of UC after autologous PBSCT in this patient. J Am Acad Dermatol, 2001 Nov, 45(5), S188 - 94 Analysis of common side effects of isotretinoin; McLane J; Patients with severe recalcitrant nodular acne that is unresponsive to conventional therapy (including topical and systemic antibiotics) have few alternative effective treatment modalities other than the use of oral isotretinoin (Accutane) . The cause of acne vulgaris is multifactorial, but the pathogenesis of this disorder of the pilosebaceous follicles arises mainly from endogenous factors . It is usually, but not always, associated with the onset of puberty . Severe acne, defined by the prevalence of facial and truncal inflammatory lesions, is a disfiguring disease that can often result in significant permanent scarring after the healing of deep inflammatory lesions and other disorders, such as systemic bacterial infections . Topical treatments are considered as the first line of therapy for less severe forms of acne, although systemic treatments such as antibiotics or antiandrogen agents are effective for either mild or moderate forms and sometimes effective for severe acne . However, in many patients with large numbers of nodules, longer treatment periods with these agents are required to reduce the count of inflammatory lesions . It has become increasingly evident that (because topical agents and antibiotic or antiandrogenic therapy have a slow onset of action) even mild or moderate acne that is treated in this way can result in scarring . In addition, the excessive use of systemic antibiotics has led to the detection of increasing numbers of antibiotic-resistant bacteria on the skin of patients with acne.(1) Therefore, because of its relatively rapid onset of action and its high efficacy with reducing more than 90% of the most severe inflammatory lesions, Accutane has a role as an effective treatment in patients with severe acne that is recalcitrant to other therapies. J Pept Res, 2001 Oct, 58(4), 317 - 24 Partial {alphaMe}Aun scan of {l-Leu11-OMe}-trichogin GA IV, a membrane active synthetic precursor of the natural lipopeptaibol; Peggion C et al.; We synthesized using solution-phase methods three analogs of {l-Leu11-OMe} trichogin GA IV, a membrane active synthetic precursor of the lipopeptaibol antibiotic in which the N-terminal n-octanoyl group and each of the three Aib residues in positions 1, 4 and 8 are replaced by an acetyl group and the lipophilic Calpha,alpha-disubstituted glycine l-(alphaMe)Aun, respectively {partial (alphaMe)Aun scan} . FT-IR absorption and CD analyses unequivocally show that the main three-dimensional structural features of {l-Leu11-OMe} trichogin GA IV are preserved in the analogs . Also, {l-Leu11-OMe} trichogin GA IV and the three Nalpha-acetylated l-(alphaMe)Aun analogs exhibit strictly comparable membrane-modifying properties . Taken together, these results strongly favor the conclusion that a shift of the long hydrocarbon moiety from the Nalpha-blocking group to the side-chain of the 1, 4 or 8 residue does not have any significant effect on the conformational properties or the membrane activity of {l-Leu11-OMe} trichogin GA IV and, by extension, of the natural lipopeptaibol. Mol Biol (Mosk), 2001 Sep-Oct, 35(5), 868 - 78 {Analysis of complex formation of daunomycin with the deoxyhexanucleotide 5'-d(TpApCpGpTpA) in an aqueous solution from NMR-spectroscopy data}; Veselkov AN et al.; Self-association of hexadeoxynucleotide 5'-d(TpApCpGpTpA) and its complexation with antitumor antibiotic daunomycin were studied by one- and two-dimensional homonuclear 1H NMR spectroscopy and heteronuclear 1H-31P NMR spectroscopy in water-salt solution . The concentration and temperature dependences of proton chemical shifts of the hexadeoxynucleotide and the ligand were measured, and equilibrium constants and thermodynamic parameters of corresponding reactions were calculated on this basis using models for the formation of hexadeoxynucleotide duplex and its complex with the antibiotic . The spatial structure of daunomycin-d(TACGTA)2 complex in solution was calculated using X-PLOR software on the basis of 2D NOE spectral data and the limit values of proton chemical shifts of the ligand . Comparative analysis of different intermolecular interactions in sequence-specific binding of the antibiotic to the DNA fragment was carried out. Cardiovasc Surg, 2001 Dec, 9(6), 595 - 9 Effect of retroviral transduction of canine microvascular endothelial cells on beta(1) integrin subunit expression and cell retention to PTFE grafts; Grandas OH et al.; This study evaluated the effect of retroviral transduction on canine microvascular endothelial cell (CMVEC) detachment from fibrin glue coated expanded polytetrafluoroethylene (ePTFE) graft material . CMVEC were isolated from adipose tissue by fluorescent activated cell sorting (FACS) . Three treatment groups were evaluated: G-I, transduced CMVEC, selected in antibiotic G418 for 10 days (n=5); G-II, CMVEC selected in G418 and recovered from selection for 4 days (n=5); and G-III, control group of naive CMVEC (n=6) . (3)H-thymidine labeled endothelial cells were seeded on fibrin glue coated four-mm diameter PTFE . Grafts were exposed to physiologic shear stresses of 16 dyn/cm(2) . Cell detachment was determined by (3)H-thymidine counts in the circuit effluent . beta(1) integrin subunit expression was measured by flow cytometry . After 2 hours of flow exposure, G-I and G-II demonstrated significantly greater cell detachment rates compared with the control seeded grafts . Median peak channel beta(1) integrin subunit value for G-III CMVEC was 2311+/-481.7 vs . 31.5+/-4.51 and 26.3+/-2.0 in the transduced cell groups (p=0.00043) . Low beta(1) integrin expression correlated with flow induced high detachment rates of retrovirally-transduced CMVEC. Clin Orthop, 2001 Oct, (391), 162 - 70 Foot and ankle infections after surgery; Donley BG et al.; Infection after foot and ankle surgery or trauma can range from the common superficial cellulitis to the less common deep soft tissue or bone infections that can have disastrous consequences . The emergence of antibiotic-resistant organisms has made treatment of infection more difficult, even though promising new antibiotics are being developed . Prevention of infection, through proper patient selection and meticulous surgical technique, is essential to satisfactory outcomes. J Heart Valve Dis, 2001 Sep, 10(5), 689 - 90 Prosthetic valve endocarditis in a patient with Marfan's syndrome following acupuncture; Nambiar P et al.; Active prosthetic valve endocarditis (PVE) as a complication of acupuncture requiring valve surgery has not been reported previously . We report a case of PVE in a patient with Marfan's syndrome as a complication of acupuncture, who underwent emergency redo aortic root and valve replacement with a homograft . This report highlights the need for prophylactic antibiotics before acupuncture in patients with prosthetic valves, and also describes the use of a homograft as an effective surgical strategy. Laryngorhinootologie, 2001 Oct, 80(10), 617 - 9 {Infected epidermoid cyst as cause of peripheral facial palsy . A case report}; Streppel M et al.; BACKGROUND: Extratemporal processes are rare causes of peripheral facial palsy . Only 17 cases of facial palsy in association with a suppurative or necrotic parotitis are reported in the literature . PATIENT AND RESULTS: We present a case of a peripheral facial palsy initiated by an infection of a epidermoid cyst, which consecutively involved the whole parotid gland . After abscess drainage and antibiotic therapy the inflammation process receded . The palsy persisted over a period of 4 weeks but improved completely . CONCLUSIONS: As the facial nerve was not enclosed by the abscess formation the palsy must have been caused indirectly . It may be assumed the inflammation spread into the Fallopian canal through the stylomastoid foramen and caused a metabolic imbalance similar to the supposed vicious circle for Bell's palsy . Due to the relapse tendency of inflammations of epidermoid cysts it is recommended to remove the entire cyst. Haematologica, 2001 Oct, 86(10), 1087 - 94 Comparative cost analysis of autologous peripheral blood progenitor cell and bone marrow transplantation in pediatric patients with malignancies; Vicent MG et al.; BACKGROUND AND OBJECTIVES: This study was conducted in order to compare and analyze clinical and economic outcomes of autologous transplantation using bone marrow or peripheral blood as the source of hematopoietic progenitor cells in pediatric patients with malignancies . DESIGN AND METHODS: We collected clinical information and resource utilization from 131 consecutive autologous transplantations (102 peripheral blood progenitor cell (PBPC) and 29 bone marrow (BM) transplants) at a single institution between January 1989 and December 1998 in children with a variety of malignancies . Multivariable linear regression was used to evaluate the associations between pre-transplantation variables, post-infusion events and overall costs . A cost-effectiveness analysis of transplantation for acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) patients was also performed . RESULTS: Hematopoietic recovery was faster in the PBPCT group (days to neutrophil and platelet engraftment: 9 and 13, respectively, versus 14 and 21 for BMT, p<0.0001).There were less transfusion, antibiotic and parenteral nutrition requirements and hospital stay was shorter (median 17 days; range 8-38) in the PBPCT group than in the BMT one (median 28 days; range 11-65) (p<0.0001) resulting in a median lower overall cost for PBPCT (US$ 7895) compared to BMT (US$ 11820)(p<0.0001) . Major determinants of overall costs for both groups were total body irradiation (TBI)-based conditioning regimen, days of hospitalization and number of transfused platelets . In PBPCT patients, a graft containing > or = 5 x 10(6)/kg CD34+ cells decreased the total cost of transplantation by 27% . Cost-effectiveness was higher for PBPCT than BMT for pediatric AML patients (p<0.0001) whereas in ALL patients the cost-effectiveness of the two transplant strategies was not significantly different . INTERPRETATIONS AND CONCLUSIONS: We conclude that, compared to BMT, autologous PBPCT in children is associated not only with clinical benefits but also economic advantages. Trends Biotechnol, 2001 Nov, 19(11), 449 - 56 Altering the glycosylation pattern of bioactive compounds; Mendez C et al.; Many bioactive natural products are glycosylated compounds in which the sugars are important or essential for biological activity . The isolation of several sugar biosynthesis gene clusters and glycosyltransferases from different antibiotic-producing organisms, and the increasing knowledge about these biosynthetic pathways opens up the possibility of generating novel bioactive compounds through combinatorial biosynthesis in the near future . Recent advances in this area indicate that antibiotic glycosyltransferases show some substrate flexibility that might allow us to alter the types of sugar transferred to the different aglycons or, less frequently, to change the position of its attachment. Biochemistry, 2001 Oct 23, 40(42), 12712 - 8 Elementary steps in the acquisition of Mn2+ by the fosfomycin resistance protein (FosA); Bernat BA et al.; The fosfomycin resistance protein, FosA, catalyzes the Mn(2+)-dependent addition of glutathione to the antibiotic fosfomycin, (1R,2S)-epoxypropylphosphonic acid, rendering the antibiotic inactive . The enzyme is a homodimer of 16 kDa subunits, each of which contains a single mononuclear metal site . Stopped-flow absorbance/fluorescence spectrometry provides evidence suggesting a complex kinetic mechanism for the acquisition of Mn(2+) by apoFosA . The binding of Mn(H(2)O)(6)(2+) to apoFosA alters the UV absorption and intrinsic fluorescence characteristics of the protein sufficiently to provide sensitive spectroscopic probes of metal binding . The acquisition of metal is shown to be a multistep process involving rapid preequilibrium formation of an initial complex with release of approximately two protons (k(obsd) > or = 800 s(-1)) . The initial complex either rapidly dissociates or forms an intermediate coordination complex (k > 300 s(-1)) with rapid isomerization (k > or = 20 s(-1)) to a set of tight protein-metal complexes . The observed bimolecular rate constant for formation of the intermediate coordination complex is 3 x 10(5) M(-1) s(-1) . The release of Mn(2+) from the protein is slow (k approximately 10(-2) s(-1)) . The kinetic results suggest a more complex chelate effect than is typically observed for metal binding to simple multidentate ligands . Although the addition of the substrate, fosfomycin, has no appreciable effect on the association kinetics of enzyme and metal, it significantly decreases the dissociation rate, suggesting that the substrate interacts directly with the metal center. Toxicol Appl Pharmacol, 2001 Oct 15, 176(2), 101 - 9 Novel effects of minocycline on Ca(2+)-dependent Cl(-) secretion in human airway epithelial Calu-3 cells; Ito Y et al.; The present study concerns previously unreported effects of the antibiotic minocycline on the transepithelial Cl(-) transport in Calu-3 cells, which display electrophysiological properties consistent with human airway serous cells . Basolateral 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 200 microM) augmented Cl(-) secretion, which was detected as a 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB, 100 microM, a Cl(-) channel blocker)-sensitive short-circuit current (I(sc)) . The DIDS-induced I(sc) was composed of Ca(2+)-activated K(+) (K(Ca)) channel-dependent and -independent components . The former was selectively inhibited by 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA/AM, 10 microM), charybdotoxin (ChTx, 100 nM), clotrimazole (10 microM), basolateral Ca(2+) removal, and basolateral minocycline (IC(50) = 20 microM) . The latter was attenuated by basolateral BaCl (5 mM) . In contrast, forskolin (10 microM)-induced I(sc), which is insensitive to BAPTA/AM and ChTx, was unaffected by minocycline (100 microM) . ATP-induced I(sc) was partially inhibited by basolateral but not by apical minocycline . I(sc) due to basolateral application of ionomycin (1 microM) was markedly suppressed by NPPB and basolateral Ca(2+) removal . These inhibitory effects were mimicked by minocycline applied only from the basolateral side of the monolayer . In the basolateral absence of Ca(2+), 1-ethyl-2-benzimdazolinone (500 microM), a K(Ca) channel opener, generated a sustained I(sc) sensitive to ChTx . Minocycline had no significant effect on the ChTx-sensitive component of the I(sc) . It is concluded that minocycline inhibits K(Ca) channel-dependent Cl(-) secretion via a blockade of Ca(2+) influx across the basolateral membrane from the extracellular side . Antimicrob Agents Chemother, 2001 Nov, 45(11), 3084 - 91 Emergence of reduced susceptibility and resistance to fluoroquinolones in Escherichia coli in Taiwan and contributions of distinct selective pressures; McDonald LC et al.; A survey of 1,203 Escherichia coli isolates from 44 hospitals in Taiwan revealed that 136 (11.3%) isolates were resistant to fluoroquinolones and that another 261 (21.7%) isolates had reduced susceptibility . Resistance was more common in isolates responsible for hospital-acquired (mostly in intensive care units) infections (17.5%) than in other adult inpatient (11.4%; P = 0.08) and outpatient isolates (11.9%; P > 0.1) . Similarly, reduced susceptibility was more common in isolates responsible for hospital-acquired infections (30.9%) than in other adult inpatient (21.0%; P = 0.04) and outpatient (21.4%; P = 0.06) isolates . Isolates from pediatric patients were less likely to be resistant (1.3 versus 12.0%; P < 0.01) but were nearly as likely to have reduced susceptibility (17.7 versus 21.9%; P > 0.1) as nonpediatric isolates . There was an inverse relationship in the proportion of isolates that were resistant versus the proportion that had reduced susceptibility among isolates from individual hospitals (R = 0.031; P < 0.05) . In an analysis of isolates from two hospitals, all 9 resistant strains possessed double point mutations in gyrA and all 19 strains with reduced susceptibility strains had single point mutations; no mutations were found among fully susceptible strains . Risk factors for resistance included underlying cancer (odds ratio {OR}, 83; 95% confidence interval {CI(95)}, 7.3 to 2,241; P < 0.001), exposure to a quinolone (OR, undefined; P = 0.02), and exposure to a nonquinolone antibiotic (OR, 20; CI(95), 2.2 to 482; P < 0.001); underlying cancer was the only independent risk factor (OR, 83; CI(95), 8.6 to 807; P < 0.001) . There were no significant associations between any of these factors and reduced susceptibility . Whereas acute and chronic quinolone use in cancer patients is a major selective pressure for resistance, other undetermined but distinct selective pressures appear to be more responsible for reduced susceptibility to fluoroquinolones in E . coli. Med Microbiol Immunol (Berl), 2001 Sep, 189(4), 193 - 200 Characterization of the cellular and humoral immune response to outer surface protein C and outer surface protein 17 in children with early disseminated Lyme borreliosis; Pohl-Koppe A et al.; OspC and Osp17 are immunodominant proteins of Borrelia burgdorferi eliciting a clear humoral immune response in adult patients with systemic Lyme disease . In this study, the cellular immune response to B . burgdorferi and the major outer surface proteins OspC and Osp17 was investigated in children during the course of early disseminated B . burgdorferi infection . Lymphoproliferative responses to recombinant proteins were compared to the protein-specific humoral immune reaction . OspC induced a clear antibody response but elicited an even stronger cellular immune response . In contrast, a cellular as well as humoral immune reaction to Osp17 was only rarely detected . Follow-up examinations demonstrated that the lymphoproliferative response to B . burgdorferi and OspC persisted for several months after antibiotic therapy . Here, we show that in early disseminated Lyme disease of childhood, OspC is a potent antigen influencing both the humoral and cellular immunity, while Osp17 plays only a minor role in immune activation. Singapore Med J, 2001 Jul, 42(7), 317 - 21 Efficacy of a nitroimidazole containing tripletherapy regime in Singapore; Ling KL et al.; BACKGROUND: There has been a gradual increase in the proportion of Singapore patients with metronidazole resistant strains of Helicobacter pylori . We studied the efficacy of a nitroimidazole containing regime in eradicating H . pylori . METHODS: Consecutive treatment naive patients with peptic ulcer disease and culture proven H . pylori were recruited . From each patient, two antral biopsies were taken for rapid urease test and two for histology . Two biopsies each from the gastric antrum and corpus were taken for H . pylori culture . Antibiotic sensitivity to amoxycillin, metronidazole, clarithromycin and tetracycline were tested using the disc diffusion method . Patients were treated with lansoprazole 30 mg bd, tinidazole 500 mg bd and clarithromycin 500 mg bd for seven days . Successful eradication was defined as either negative urea breath tests 4 and 12 weeks after treatment, or negative histology and culture at least four weeks after the end of treatment . RESULTS: A total of 64 patients were culture positive (51 males, 13 females) . Forty-two patients had duodenal ulcers (DU), 17 gastric ulcers (GU), and 5 DU and GU . Metronidazole resistance was detected in 16 patients (25%) . Three of the 16 patients (19%) had a mixed population of resistant and sensitive strains of H . pylori . None of the H . pylori isolates were resistant to amoxycillin, tetracycline or clarithromycin . Overall, eradication was achieved in 51/64 patients (80%) . Eradication rate was 88% (42/48) among those with metronidazole sensitive strains, and 56% (9/16) among those with metronidazole resistant strains (p < 0.02) . CONCLUSION: A high proportion of our patients with metronidazole resistant strains of H . pylori failed eradication therapy when a nitroimidazole containing regime was used . It may not be appropriate to use a nitroimidazole containing without prior knowledge of the antibiotic sensitivity pattern of the H . pylori isolate. Rev Invest Clin, 2001 Jul-Aug, 53(4), 335 - 9 Induction of tumor necrosis factor-alpha by cefodizime in U-937 cells; Guerra-Infante FM et al.; Cefodizime has modulating effects on the release of diverse cytokines . We determined the modulator activity of this antibiotic on the production of TNF in human monocytic U-937 cells . The measurement of TNF was carried out by ELISA test and by a L-929 cells-based citotoxic bioassay . The results showed that cefodizime alone induced the production of TNF on U-937 cells, however, the addition of LPS led to a decrease in the release of this cytokine (p < 0.05) . On the other hand, the combination of cefodizime-PMA had a synergic effect (p < 0.05), while addition of LPS to this combination caused a decrease of TNF production (p < 0.05) . With these results we conclude that cefodizime modulates the production of TNF in U-937 cells, which is down regulated by the addition of LPS. Rev Stomatol Chir Maxillofac, 2001 Aug, 102(5), 266 - 9 {Extra-oral implants and irradiation: current trends}; Benateau H et al.; Recommended treatment for head and neck cancer associates surgery and radiotherapy . Indication for bone-anchored epitheses in irradiated patients is also a common situation . The outcome of the implant appears to be improved with a special protocol for hyperbaric oxygen therapy, antibiotic therapy and calcitherapy . The problem of radiotherapy in patients with titanium osseointegrated implants is also discussed. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2001 Oct, 92(4), 394 - 8 Treatment of chronic osteomyelitis in Korea; Kim SG et al.; OBJECTIVE: We sought to investigate the clinical and histopathologic features of chronic osteomyelitis and its treatment in Koreans . STUDY DESIGN: A total of 49 patients (ages 11-79 years; mean, 47.3 years) were examined in this retrospective chart review . In a new treatment protocol used for 39 patients, chronic osteomyelitis of the jaws was treated by surgical intervention and 2 weeks of intravenous antibiotics, followed by 6 weeks of oral antibiotics, whereas a control group consisting of 10 patients was treated by surgery alone . Surgical therapy consisted of decortication or sequestrectomy and saucerization of the affected bone . A successful outcome was defined as the resolution of symptoms after surgery alone or after surgery and 8 weeks of antibiotic therapy . Failure was defined as a case requiring a second operation and 8 additional weeks of antibiotic therapy . RESULTS: A successful outcome was seen in 94.9% of patients on the new treatment protocol, as well as in 60% of control patients . A purulent discharge developed in 2 cases after the new treatment protocol and in 4 control cases, but the patients were treated successfully with a second operation . CONCLUSIONS: Surgery followed by antibiotic therapy for at least 8 weeks is an effective method for treating chronic osteomyelitis of the jaws. Dis Colon Rectum, 2001 Oct, 44(10), 1537 - 49 Bowel preparation for colorectal surgery; Zmora O et al.; PURPOSE: The aim of this study was to assess recent literature regarding bowel preparation for colonoscopy and surgery . METHODS: The study was conducted by an Index Medicus English-language search of articles relevant to both oral mechanical and parenteral and oral antibiotic preparation for elective colorectal surgery and mechanical bowel preparation for colonoscopy . The study period was from 1975 to 2000 . In addition, studies of elective colorectal surgery without mechanical bowel preparation were also considered . RESULTS: Although several recent prospective, randomized trials have suggested that elective colorectal surgery can be safely performed without any mechanical bowel preparation, mechanical bowel preparation remains the standard of care, at least in North America at the present time . A recent survey of the members of The American Society of Colon and Rectal Surgeons revealed that the majority currently use sodium phosphate for bowel preparation and use a dual oral antibiotic regimen before elective colorectal surgery, combined with two doses of parenteral antibiotics . Although some of the use patterns are based on prospective, randomized study, others seem founded strictly on habit and theory . CONCLUSIONS: The current methods of bowel cleansing for both colonoscopy and surgery include sodium phosphate and polyethylene glycol; colorectal surgeons practicing in North America currently prefer sodium phosphate . Additional preparation for colorectal surgery includes perioperative parenteral antibiotics and, to a slightly lesser degree, preoperative oral antibiotic preparation . Although some recent prospective, randomized studies have suggested that omission of mechanical bowel preparation for elective colorectal surgery is not only feasible but potentially preferable, caution is recommended before routinely omitting these widely practiced measures, because data to support such routine omission are limited. Infect Immun, 2001 Nov, 69(11), 6887 - 92 Determination of the infectious dose of Helicobacter pylori during primary and secondary infection in rhesus monkeys (Macaca mulatta); Solnick JV et al.; We sought to determine the infectious dose of Helicobacter pylori during primary and secondary infection in the rhesus monkey and to determine whether preinoculation acid suppression is necessary to produce colonization . Mixed inoculation with three human-derived strains showed that H . pylori J166 is particularly adapted to colonization of rhesus monkeys, since it outcompeted two other strains . The minimum infectious dose of H . pylori J166 was 10(4) bacteria in specific-pathogen (H . pylori)-free monkeys . Rechallenge of these monkeys after antibiotic therapy was characterized by a 10- to 100-fold decrease in bacterial load compared to primary infection, but with little change in the infectious dose . Acid suppression prior to inoculation was not necessary for colonization to occur . These results provide a basis for future animal experiments using more ecologically relevant conditions of inoculation and suggest that reduction in bacterial load rather than complete protection may be a more realistic goal for H . pylori vaccination. Am J Physiol Lung Cell Mol Physiol, 2001 Nov, 281(5), L1123 - 9 Chlorzoxazone or 1-EBIO increases Na(+) absorption across cystic fibrosis airway epithelial cells; Gao L et al.; Previous studies demonstrated that chlorzoxazone or 1-ethyl-2-benzimidazolinone (1-EBIO) enhances transepithelial Cl(-) secretion by increasing basolateral K(+) conductance (G(K)) (Singh AK, Devor DC, Gerlach AC, Gondor M, Pilewski JM, and Bridges RJ . J Pharmacol Exp Ther 292: 778-787, 2000) . Hence these compounds may be useful to treat cystic fibrosis (CF) airway disease . The goal of the present study was to determine whether chlorzoxazone or 1-EBIO altered ion transport across Delta F508-CF transmembrane conductance regulator homozygous CFT1 airway cells . CFT1 monolayers exhibited a basal short-circuit current that was abolished by apical amiloride (inhibition constant 320 nM) as expected for Na(+) absorption . The addition of chlorzoxazone (400 microM) or 1-EBIO (2 mM) increased the amiloride-sensitive I(sc) approximately 2.5-fold . This overlapping specificity may preclude use of these compounds as CF therapeutics . Assaying for changes in the basolateral G(K) with a K(+) gradient plus the pore-forming antibiotic amphotericin B revealed that chlorzoxazone or 1-EBIO evoked an approximately 10-fold increase in clotrimazole-sensitive G(K) . In contrast, chlorzoxazone did not alter epithelial Na(+) channel-mediated currents across basolateral-permeabilized monolayers or in Xenopus oocytes . These data further suggest that alterations in basolateral G(K) alone can modulate epithelial Na(+) transport. Eur J Cancer, 2001 Nov, 37(16), 2121 - 8 Rapamycin increases the cellular concentration of the BCL-2 protein and exerts an anti-apoptotic effect; Calastretti A et al.; The immunosuppressant rapamycin, an immunophilin-binding antibiotic, has been studied in follicular B-cell lymphoma lines that express the highest level of the BCL-2 protein . The growth rate of human follicular B-cell lymphoma lines was slowed more efficiently than that of other human B-cell lines or non-B-cell lines . This effect was dependent on the arrest of cells in the G(1) phase; the number of apoptotic cells was not increased . Rapamycin inhibited apoptosis or caspase activation induced by cytotoxic drugs, whereas caspase activation by doxorubicin was not inhibited . The increase in the cellular concentration of BCL-2 protein was related to its concentration in the steady state and was unrelated to the amount of bcl-2 mRNA . The increase of BCL-2 level in the cells rather than its level in the steady state may be important for drug resistance . The biochemical target of rapamycin, the mTOR kinase, may be a candidate sensitising agent for chemotherapy . This effect of rapamycin shows that G(1) arrest and protection from apoptosis are combined events susceptible to regulation by pharmacological means. Cancer, 2001 Oct 15, 92(8), 2172 - 80 A lipophilic vasoactive intestinal peptide analog enhances the antiproliferative effect of chemotherapeutic agents on cancer cell lines; Gelber E et al.; BACKGROUND: Vasoactive intestinal peptide (VIP) is one of several small neuropeptides that affect cancer growth . A lipophilic VIP analog, stearyl-Nle(17)-neuroten-sin(6-11)VIP(7-28) (SNH) that inhibited lung carcinoma growth has been described previously . The experiments performed were clonogenic assays in vitro and tumor xenografts in nude mice in vivo . These studies were now extended to colon carcinoma and to combination therapy with chemotherapeutic agents . METHODS: Assays were performed with cell lines, and tumor proliferation was assessed using the (3-{4,5-dimethylthiazol-2-yl-5}-{3-carboxymethoxyphenyl}-2-{4-sulfophenyl}-2H tetrazolium) (MTS) colorimetric assay for mitochondrial function of living cells . RESULTS: The lipophilic analog (SNH) enhanced the antiproliferative activity of diverse chemotherapeutic agents: doxorubicine (antibiotic); vinorelbine (vinca alkaloid, antimicrotubule formation); paclitaxel (antimicrotubule agent); gemcitabine (antimetabolite); irinotecan (topoisomerase I inhibitor); and cisplatin (platinum compound acting as an alkylating agent) . In all cases, the antiproliferative effect of SNH and the chemotheraputic agent was at least additive and for some combinations and concentrations even synergistic . For example, 2 microM of the antagonist that produced a 15-20% growth inhibition in the nonsmall cell lung carcinoma cell line reduced the IC(50) by 2-4-fold for most of the chemotherapeutic agents tested . Higher analog concentrations were even more efficacious . Similar results were obtained with colon carcinoma cell lines . CONCLUSIONS: Chemotherapeutic treatment of advanced solid tumors, such as nonsmall cell lung carcinoma, colon carcinoma, or prostate carcinoma, achieves a response rate of between 10% and 30% with significant toxicity . Combination therapy with the lipophilic VIP analog SNH and the preferred chemotherapeutic agent may greatly enhance the response rate, and by permitting a dose reduction, should significantly reduce side effects . Bone, 2001 Oct, 29(4), 331 - 5 Human bone marrow stromal cells are efficiently transduced by vesicular stomatitis virus-pseudotyped retrovectors without affecting subsequent osteoblastic differentiation; Liu P et al.; This study tested the transduction efficiency of human bone marrow stromal cells (hBMSCs) with vesicular stomatitis virus (VSV)-pseudotyped retrovectors and their subsequent osteogenic differentiation in vitro . Two different retrovectors encoding beta-galactosidase (beta-gal) or enhanced green fluorescent protein (eGFP) as marker genes were examined for transduction of hBMSCs . hBMSCs were obtained from bone marrow filtrates of normal donors (aged 5-35 years), cultured in alpha-minimal essential medium (alpha-MEM) containing 10% fetal calf serum and infected with retrovectors soon after the adherent cells started to form individual colonies . Transduced hBMSCs were observed to express eGFP protein 4-7 days after infection in primary cultures, and the majority of hBMSCs were eGFP-positive . hBMSCs were also stained for beta-gal in the secondary cultures and virtually all hBMSCs expressed beta-gal activity . Transduced hBMSCs were examined for their osteogenic potential . These cells were found to express markers of osteogenic differentiation, including alkaline phosphatase, type I collagen, bone sialoprotein, decorin, and osteocalcin, as strongly as uninfected control cells . Mineralization was also induced by dexamethasone in transduced cells as well as control cells . These results demonstrate that hBMSCs are highly susceptible to infection with VSV-pseudotyped retrovectors with the majority of cultured cells expressing the viral transgenes without antibiotic selection . Transduced cells retain their osteogenic potential in vitro . hBMSCs are a promising cellular vehicle for systemic human gene therapy and VSV-pseudotyped retrovectors should be effective for their in vitro transduction prior to cellular engraftment. J Physiol Paris, 2001 Jan-Dec, 95(1-6), 137 - 40 Endogenous bacteria-triggered inducible nitric oxide synthase activation protects the ovariectomized rat stomach; Morschl E et al.; Under experimental circumstances, ovariectomy attenuates gastric mucosal injury where nitric oxide (NO)-mediated pathways are involved . In this study, we have examined the changes in constitutive (cNOS) and inducible NO synthase (iNOS) enzyme activities (assessed by the citrulline assay), and the role of endogenous bacteria in ovariectomy-provoked mucosal defence . Gastric lesions were induced by indomethacin (50 mg/kg, s.c.) over a 4 h period in sham-operated and ovariectomized female Wistar rats . Groups of animals received the wide-spectrum antibiotic ampicillin (800 mg/kg/day, p.o., for 3 days), and others were injected with bacterial endotoxin (E . coli, 3 mg/kg, i.v., 5 h before autopsy) . We found that ovariectomy increased iNOS and decreased cNOS activity (resulting an elevated total gastric NOS level), and protected the stomach, effects reversed by ampicillin treatment . In ovary-intact rats, administration of bacterial endotoxin enhanced gastric iNOS activity and reduced lesion-formation . These results suggest that ovariectomy improves gastric mucosal defence perhaps by endogenous bacteria-triggered induction of iNOS. Org Lett, 2001 Oct 18, 3(21), 3273 - 5 First stereocontrolled synthesis of (S)-cleonin and related cyclopropyl-substituted amino acids; Esposito A et al.; {reaction: see text} . Enantiomerically pure (S)-cleonin, a key component of the antitumor antibiotic cleomycin, was prepared starting from (R)-serine . The Kulinkovich cyclopropanation of the methyl ester of N-Cbz serine acetonide gave the hydroxycyclopropyl moiety . The amino alcohol region was further oxidized to amino acid . The Kulinkovich cyclopropanation allowed also the preparation of other non-natural substituted cyclopropylglycines. Arq Neuropsiquiatr, 2001 Sep, 59(3-B), 824 - 8 {Cerebellar abscess treated by clinical management: case report}; Vialogo JG et al.; We report a case of cerebellar abscess secondary to chronic otitis and localized in the right cerebellar hemisphere, in a pediatric patient . The abscess was treated only by antibiotic therapy, evolving to complete clinical and radiological resolution, without neurosurgical intervention . We also discuss the pathogenesis, histopathogenesis, clinical manifestations and the forms of treatment of CNS abscesses. Neurol India, 2001 Sep, 49(3), 262 - 6 Intracranial infective aneurysms: angiographic evaluation with treatment; Kovoor JM et al.; Infective intracranial aneurysms are relatively uncommon . They develop due to septic embolisation of the vasa vasorum or lumen of the artery, with resultant focal arteritis and necrosis, leading to aneurysm formation . They are an important cause for intracranial haemorrhage . Six cases of infective aneurysms are described . A focus of infection could be detected in all the patients . Surgery was done in three cases, out of which two patients made significant recovery, while one patient died in the immediate postoperative period . Out of the three cases, treated conservatively with antibiotic therapy, there was total resolution on follow up angiogram in two, while one patient was lost to follow up. Crit Care Med, 2001 Oct, 29(10 Suppl), S231 - 6 Heart failure in pediatric septic shock: utilizing inotropic support; Tabbutt S; Septic shock presents a unique challenge in the pediatric patient . Sepsis stimulates the release of inflammatory mediators that can compromise cardiac function . Oxygen extraction abnormalities, diminished responses to adrenergic agonists, and impaired ventricular function often result . After fluid resuscitation and antibiotic therapy, careful cardiovascular assessment is needed to administer appropriate inotropic and vasoactive drugs. J Surg Res, 2001 Oct, 100(2), 211 - 6 Effect of harvesting and sorting on beta-1 integrin in canine microvascular cells; Piercy KT et al.; BACKGROUND: The goal of seeding prosthetic conduits with endothelial cells (ECs) has focused attention on the role of EC adhesion molecules . Cell preparation techniques may affect adhesion molecule expression and graft seeding . METHODS: Using fluorescent antibody labeling and flow cytometric analysis, this study examined the effectsof monolayer detachment (scraping vs trypsinization), timing of immunolabeling (pre- vs postdetachment), gene transfection (transfected vs nontransfected), and cell selection (antibiotic vs fluorescence sorting) techniques on beta-1 integrin expression in canine microvascular EC (K9MVEC) . RESULTS: Cell scraping resulted in a significantly higher beta-1 integrin mean fluorescence intensity than did cell trypsinization (P < 0.05) . No difference was observed with immunolabeling prior to versus following monolayer harvesting . Gene transfection had no significant effect on beta-1 integrin expression . No advantage was observed between cell selection methods (P > 0.05) . CONCLUSION: This study suggests that the monolayer harvesting technique employed has a significant impact on beta-1 integrin quantification by flow cytometric analysis . Furthermore, microvascular EC expression of beta-1 integrin was not adversely affected by gene transfection . Aust N Z J Obstet Gynaecol, 2001 Aug, 41(3), 295 - 302 Ten-year review of hysterectomy morbidity and mortality: can we change direction? Varol N, Healey M, Tang P, Sheehan P, Maher P, Hill D. The medical records of all women who underwent hysterectomy for benign disease performed between 1986 and 1995 were reviewed to ascertain the incidence of morbidity and mortality of abdominal, vaginal, and laparoscopically assisted vaginal hysterectomy at a university teaching hospital . A total of 1940 hysterectomies were performed during this period; 74% of hysterectomies were performed abdominally, 24% vaginally and 2% were laparoscopically assisted . In 80% of the patients uterine leiomyomas, adenomyosis, dysfunctional uterine bleeding or uterine prolapse were the indications for hysterectomy The overall complication rate was 44% for abdominal hysterectomy (AH) and 27.3% for vaginal hysterectomy (VH) . An unintended major surgical procedure was required in 3% and 1% of women undergoing AH and VH respectively The rate of return to the operating room for haemostasis was 0.6% for AH and 0.2% for VH . The AH group was four times more likely than the VH group to require surgical intervention (36% versus 9%) at readmission . Vaginal hysterectomy was associated with a lower febrile morbidity and minor complication rate . Prophylactic antibiotics reduced the febrile morbidity for VH and AH by 50% (Student's t-test, p = 0.02) and 40% (Student's t-test, p < 0.001) respectively The overall mortality rate was 1.5 per 1000. Biol Chem, 2001 Aug, 382(8), 1215 - 25 Biophysical characterization of lipopolysaccharide and lipid A inactivation by lactoferrin; Brandenburg K et al.; The interaction of bacterial endotoxins (LPS Re and lipid A, the 'endotoxic principle' of LPS) with the endogenous antibiotic lactoferrin (LF) was investigated using various physical techniques and biological assays . By applying Fourier-transform infrared (FTIR) spectroscopy, we find that LF binds to the phosphate group within the lipid A part and induces a rigidification of the acyl chains of LPS . The secondary structure of the protein - as monitored by the amide I band - is, however, not changed . Concomitant with the IR data, scanning calorimetric data indicate a sharpening of the acyl chain phase transition . From titration calorimetric and zeta potential data, saturation of LF binding to LPS was found to lie at a {LF}:{LPS} ratio of 1:3 to 1:5 M from the former and 1:10 M from the latter technique . X-ray scattering data indicate a change of the lipid A aggregate structure from inverted cubic to multilamellar, and with fluorescence (FRET) spectroscopy, LF is shown to intercalate by itself into phospholipid liposomes and may also block the lipopolysaccharide-binding protein (LBP)-induced intercalation of LPS . The LPS-induced cytokine production of human mononuclear cells exhibits a decrease due to LF binding, whereas the coagulation of amebocyte lysate in the Limulus test exhibited concentration-dependent changes . Based on these results, a model for the mechanisms of endotoxin inactivation by LF is proposed. J Bacteriol, 2001 Nov, 183(21), 6384 - 93 Conditional-replication, integration, excision, and retrieval plasmid-host systems for gene structure-function studies of bacteria; Haldimann A et al.; We have developed a series of powerful and versatile conditional-replication, integration, and modular (CRIM) plasmids . CRIM plasmids can be replicated at medium or high copy numbers in different hosts for making gene (or mutant) libraries . They can be integrated in single copies into the chromosomes of Escherichia coli and related bacteria to study gene function under normal physiological conditions . They can be excised from the chromosome, e.g., to verify that phenotypes are caused by their presence . Furthermore, they can be retrieved singly or en masse for subsequent molecular analyses . CRIM plasmids are integrated into the chromosome by site-specific recombination at one of five different phage attachment sites . Integrants are selected as antibiotic-resistant transformations . Since CRIM plasmids encode different forms of resistance, several can be used together in the same cell for stable expression of complex metabolic or regulatory pathways from diverse sources . Following integration, integrants are stably maintained in the absence of antibiotic selection . Each CRIM plasmid has a polylinker or one of several promoters for ectopic expression of the inserted DNA . Their modular design allows easy construction of new variants with different combinations of features . We also report a series of easily curable, low-copy-number helper plasmids encoding all the requisite Int proteins alone or with the respective Xis protein . These helper plasmids facilitate integration, excision ("curing"), or retrieval of the CRIM plasmids. Urol Clin North Am, 2001 Aug, 28(3), 499 - 507 Radical retropubic prostatectomy . Preoperative management; Rosenblum N et al.; The morbidity of radical prostatectomy is minimized by identifying men who are at significant cardiovascular risk and excluding them from the procedure . Preoperative management designed to minimize surgical and medical complications and exposure to allogenic blood products increases the benefit-to-risk ratio of radical prostatectomy over other treatment options for localized prostate cancer. Oral Oncol, 2001 Dec, 37(8), 613 - 9 Periodontal disease and periodontal management in patients with cancer; Epstein JB et al.; Periodontal infection may exacerbate during cancer therapy and may result in oral pain and infection, and systemic infection, which may cause morbidity and can lead to mortality in neutropenic cancer patients . Periodontal disease in head and neck cancer patients treated with radiation therapy may lead to acute and chronic complications . The literature was reviewed by a search of Medline of the National Library of Medicine . The search was conducted to identify publications assessing periodontal disease in cancer patients . In addition, a review of papers referenced in the retrieved papers was conducted to identify additional publications for review . Periodontal disease should be assessed and managed prior to medical treatment of cancer for those with oropharyngeal cancer, and for patients in whom neutropenia may develop during treatment . Pretreatment assessment and management, and maintenance of oral hygiene have been shown to be effective in preventing oral and systemic complications during treatment . A complete oral and periodontal examination is appropriate for all patients planned to receive head and neck radiation therapy and those to be treated with medical protocols that are anticipated to result in neutropenia . Oral and periodontal care must continue following cancer therapy, and requires that the health care provider have an understanding of the malignant disease, oral manifestations of the disease, medical management of the disease, and of the oral complications that may develop. Eur J Paediatr Neurol, 2001, 5(2), 79 - 81 Bilateral subdural collections--an unusual feature of possible Kawasaki disease; Bailie NM et al.; A case of possible Kawasaki disease presenting with bilateral subdural collections is reported . A 6-month-old boy was admitted to hospital following a prolonged partial seizure . He showed signs of worsening encephalopathy and was treated for presumed infective meningoencephalitis . Imaging revealed bilateral subdural collections . Pyrexia and irritability continued despite appropriate antibiotic and antiviral therapy suggesting a vasculitic process . The mucocutaneous signs normally associated with Kawasaki disease were subtle and fleeting in this infant . There was a dramatic clinical response to intravenous immunoglobulin and high dose aspirin . At 2-year follow-up the boy has made a complete recovery with no echocardiographic evidence of coronary artery aneurysm and resolution of subdural collections . Kawasaki disease or other vasculitides should be considered in the differential diagnosis of acute subdural collections in infancy. Clin Ther, 2001 Sep, 23(9), 1589 - 600 A comparison of asthma-related expenditures for patients started on montelukast versus fluticasone propionate as monotherapy; Bukstein DA et al.; BACKGROUND: The prevalence of asthma is increasing, and this chronic condition imposes a substantial economic burden worldwide . It is not known whether newer therapies, such as leukotriene receptor antagonists (LTRAs), can ease this burden . OBJECTIVE: This analysis examined the association between choice of first-line asthma control therapy and health care resource utilization and expenditures in patients with mild asthma . METHODS: A retrospective cohort analysis of claims data for patients who started therapy with fluticasone propionate or montelukast between January 1, 1997, and February 28, 1999, was performed, adjusting for baseline differences . RESULTS: Data from 343 patients (229 fluticasone; 114 montelukast) were analyzed . Patients starting therapy with fluticasone were significantly older (33.3 vs 27.6 years; P = 0.015) and significantly less likely than patients starting therapy with montelukast to have been started on control therapy by an asthma specialist (52.0% vs 69.3%; P = 0.007) . There were no significant differences in mean changes in total asthma-related health care expenditures, oral steroid and antibiotic prescriptions, hospitalizations, or emergent care visits . The mean increase in total asthma-related pharmacy expenses was significantly greater for patients who were prescribed montelukast than for those prescribed fluticasone (P < 0.001) . Treatment adherence was better in patients prescribed montelukast versus fluticasone (5.1 vs 3.1 prescriptions filled per year, respectively; P < 0.001) . Montelukast patients had a significantly lower increase in the number of beta-agonist prescriptions filled per year than fluticasone patients (0.19 vs 0.66; P = 0.03) . In the subsequent year, 4% (10/229) of fluticasone patients added or switched to an LTRA . No montelukast patients added to or switched control therapy . CONCLUSION: The mean change in total asthma-related health care expenditures was not significantly different in patients started on fluticasone propionate versus montelukast . Montelukast patients had better adherence to their treatment regimen and required fewer beta-agonist prescriptions, which is an indicator of asthma control and possibly therapeutic effectiveness. Foot Ankle Int, 2001 Sep, 22(9), 720 - 4 Prognostic value of 99m Tc leukocyte scintigraphy in diabetic pedal osteomyelitis; Van der Wall H et al.; While leukocyte scintigraphy is accurate in detection of pedal osteomyelitis, there has been little data relating the technique to outcomes . We designed a trial to examine the prognostic value of sequential 99m Tc labeled leukocyte scans to establish the diagnosis of osteomyelitis and after three to four weeks of culture-guided antibiotic therapy . Twenty-three diabetic patients with proven pedal osteomyelitis (21/23) or persistent uptake (2/23) on the sequence of scans were studied . Five additional episodes of osteomyelitis developed in the group over the period of the study . Eleven patients demonstrated persistent uptake in the sequential scans . Nine progressed to amputation . The remaining two patients were biopsy-negative for infection, did not have cutaneous ulceration and were thought to have rapidly progressive arthropathy . Sequential leukocyte scintigraphy accurately predicts the need for amputation and can circumvent ineffective prolonged antibiotic therapy. Bull Exp Biol Med, 2001 Jun, 131(6), 589 - 94 Alterative and plastic insufficiency of cardiomyocytes: isoproterenol-induced damage to myocardium during anthracycline cardiomyopathy; Lushnikova EL et al.; The development of regenerative and plastic myocardial insufficiency induced by anthracycline antibiotic rubomycin is accompanied by a decrease in cardiomyocyte sensitivity to damage produced by synthetic catecholamine isoproterenol . The incidence and the size of coagulation necrosis foci of cardiomyocytes developed 6 h after isoproterenol injection significantly decreased with increasing in the interval between rubomycin injection and subsequent administration of isoproterenol . In Wistar rats receiving rubomycin 3-5 days prior to isoproterenol and exhibiting signs of regenerative and plastic insufficiency, no cardiomyocyte contracture, intracellular myocytolysis, or lump degradation characteristic of cardiac insufficiency induced by endo- and exogenous catecholamines were found. Chemotherapy, 2001, 47 Suppl 4, 3 - 10; discussion 26-7 Solutions for difficult diagnostic cases of community-acquired pneumonia; Fine MJ; Community-acquired pneumonia (CAP) is a common illness that creates significant burdens upon the healthcare system . Improving the quality of medical care for patients with this illness requires an evidence-based and cost-efficient treatment approach . The first step in this approach is to make an accurate diagnosis, while considering the full differential diagnosis of the illness . This requires an understanding of the sensitivity and specificity of the history and physical examination to establish the diagnosis of CAP . The second step is to quantify severity of illness, which can help physicians determine the appropriate initial site of treatment, intensity of the diagnostic evaluation, and choice of initial antibiotic therapy . Case histories are presented to outline the clinical application of an approach that uses the Pneumonia Patient Outcomes Research Team (PORT) prediction rule for prognosis to quantify the severity of illness, and recent guidelines for the management of CAP are highlighted . Onderstepoort J Vet Res, 2001 Jun, 68(2), 149 - 50 Vaccination to control an outbreak of Mycoplasma crocodyli infection; Mohan K et al.; Details of a severe outbreak of M . crocodyli infection in farmed crocodiles are reported . The outbreak was suspected to have been precipitated by translocation-related stress on the animals brought from a farm with a known history of M . crocodyli infection . Resorting to the use of an autogenous vaccine proved more effective in alleviating the disease manifestations than antibiotic therapy . Prospects of vaccination in the face of an outbreak are discussed. Med Trop (Mars), 2001, 61(1), 56 - 8 Malaria prophylaxis/radical cure: recent experiences of the Australian Defence Force; Edstein MD et al.; Since the eighties, the Australian Defence Force has deployed soldiers in malaria-endemic areas: Cambodia, Somalia, Rwanda, Bougainville, and East Timor . Currently, doxycycline is used as first line prophylactic drug and mefloquine is recommended for those who cannot tolerate the antibiotic . In 1998, the Australian Defence Force participated in the evaluation of tafenoquine for prophylaxis of both falciparum and vivax malaria in Thai soldiers . At the completion of this six-month study, 29 of 205 soldiers had come down with malaria including eight with falciparum malaria, 20 with vivax malaria, and one with mixed infection . A total of 28 of the 101 soldiers in the placebo group were infected with malaria as compared with only one of the 104 soldiers in the tafenoquine group . In 1999, another study was started on the island of Bougainville to compare the effectiveness a 3-day course of tafenoquine and a 14-day course of primaquine for radical cure of vivax malaria . At the present time, 411 soldiers have completed the study including 201 in tafenoquine arm and 210 in primaquine arm . Seven soldiers in each arm developed vivax malaria after returning to Australia . These results indicate that tafenoquine is not superior to primaquine in preventing vivax malaria . However study participants preferred the shorter course using tafenoquine and operationally it was found to be more suitable than primaquine. J Comput Assist Tomogr, 2001 Sep-Oct, 25(5), 733 - 41 Acute neck infections: prospective comparison between CT and MRI in 47 patients; Munoz A et al.; PURPOSE: The purpose of this work was to assess the advantages and disadvantages of MRI versus CT in the initial evaluation of acute infections involving the neck . METHOD: We prospectively evaluated 47 patients with neck infections . All patients underwent CT and MRI with contrast of the area of interest using similar slice thickness . Final diagnosis was achieved by percutaneous aspiration, surgical exploration and drainage, or follow-up after successful antibiotic therapy in all patients . Two radiologists reviewed all imaging studies with special attention to lesion conspicuity, location, extension, bone involvement, source of infection (odontogenic versus nonodontogenic), and presence of gas and/or calcium in the lesions . A 3 point scale was used to grade these parameters, and statistical comparison was done using paired t test . RESULTS: As used in our population, MRI was superior to CT in regard to lesion conspicuity, number of anatomic spaces involved, extension, and source . Additionally, although not statistically significantly, MRI detected a greater number of abscess collections . CT was superior to MRI in the detection of intralesional gas and calcium and showed fewer motion artifacts . These advantages of CT were, however, not significantly better than those of MRI . CONCLUSION: As used in our study, MRI was considered superior to CT in the initial evaluation of neck infections . Our findings suggest that MRI may be used as the first and perhaps the only modality to initially evaluate patients with neck infections when clinically feasible. Br J Plast Surg, 2001 Oct, 54(7), 640 - 3 Combined use of normal mode and Q-switched ruby lasers in the treatment of congenital melanocytic naevi; Kono T et al.; Melanocytic naevi are common and they are often removed for cosmetic purposes . In recent years, both the normal mode ruby laser and the Q-switched ruby laser have been used, either alone or in combination, for the removal of congenital melanocytic naevi . However, their success was restricted to partial lightening and incomplete histological clearance . We report a new approach, with combined use of normal mode and Q-switched ruby lasers, that improves the effectiveness of the laser removal of pigmentation in congenital melanocytic naevi . Curr Treat Options Neurol, 2001 Nov, 3(6), 543 - 554 Neurologic Complications of Organ Transplantation; Bashir RM; Over the past four decades, remarkable advances have been made in the field of organ transplantation . Improved surgical techniques and perioperative care have reduced the mortality and morbidity of many organ transplant procedures to acceptable levels . The creation of national and international organ registries has resulted in a more efficient system for organ procurement and use . Advances in immunology and the introduction of more potent immunomodulating agents have led to doubling of survival rates for those with transplanted grafts . Unfortunately, a high rate of neurologic complications associated with organ transplantation persists . Cerebral embolization, hypoxia, and bleeding remain frequent after heart and lung transplantation . Prolonged thrombocytopenia associated with bone marrow transplantation still leads to catastrophic cerebral hemorrhage . Although the period of neutropenia following bone marrow transplantation has been reduced by the use of growth factors, and the routine use of potent prophylactic antibiotic and antiviral agents has reduced the incidence of infection, unusual or resistant central nervous system (CNS) infections continues to arise, often creating difficult treatment choices . Furthermore, the more effective classes of immunosuppressants may have direct toxic effects on the nervous system . The major challenge for the future is to develop agents and strategies for management that can effect selective tolerance to the donated organ without paralyzing the immune system's ability to fight infection . Such agents must also have limited or no toxicity to the nervous and other organ systems . The observations by Starzl on the existence of leukocyte chimerism years after transplantation suggest that understanding and building on this natural phenomenon may hold promise for solving major problems in the field of organ transplantation. Pediatrics . 2001 Oct;108(4):E75. Development and impact of a computerized pediatric antiinfective decision support program; Mullett CJ et al.; OBJECTIVE: Computerized medical decision support tools have been shown to improve the quality of care and have been cited by the Institute of Medicine as one method to reduce pharmaceutical errors . We evaluated the impact of an antiinfective decision support tool in a pediatric intensive care unit (PICU) . METHODS: We enhanced an existing adult antiinfective management tool by adding and changing medical logic to make it appropriate for pediatric patients . Process and outcomes measures were monitored prospectively during a 6-month control and a 6-month intervention period . Mandatory use of the decision support tool was initiated for all antiinfective orders in a 26-bed PICU during the intervention period . Clinician opinions of the decision support tool were surveyed via questionnaire . RESULTS: The rate of pharmacy interventions for erroneous drug doses declined by 59% . The rate of anti-infective subtherapeutic patient days decreased by 36%, and the rate of excessive-dose days declined by 28% . The number of orders placed per antiinfective course decreased 11.5%, and the robust estimate of the antiinfective costs per patient decreased 9% . The type of anti-infectives ordered and the number of antiinfective doses per patient remained similar, as did the rates of adverse drug events and antibiotic-bacterial susceptibility mismatches . The surveyed clinicians reported that use of the program improved their antiinfective agent choices as well as their awareness of impairments in renal function and reduced the likelihood of adverse drug events . CONCLUSIONS: Use of the pediatric antiinfective decision support tool in a PICU was considered beneficial to patient care by the clinicians and reduced the rates of erroneous drug orders, improved therapeutic dosage targets, and was associated with a decreased robust estimate of antiinfective costs per patient . antiinfective agents, decision support systems, drug therapy, medication errors, child, infant. Pediatrics . 2001 Oct;108(4):E62. Preimmunization anti-pneumococcal antibody levels are protective in a majority of patients with cystic fibrosis; Lahiri T et al.; OBJECTIVE: Although invasive pneumococcal disease is infrequent in cystic fibrosis (CF), it is recommended that all patients with CF receive pneumococcal immunization . As part of a comprehensive program to immunize our clinic population, we obtained preimmunization anti-pneumococcal antibody levels . We hypothesized that the percentage of CF patients without protective levels of anti-pneumococcal antibody levels would be high, as they are exposed to frequent antibiotic therapy that may eradicate organisms before generation of an antibody response . METHODS: An observational study of 100 patients with CF, aged 1 to 39 years, was conducted in a regional CF center . Preimmunization anti-pneumococcal antibody levels against 6 serotypes were measured by enzyme-linked immunosorbent assay . Protective antibody levels were defined as >200 ng/mL . RESULTS: A majority of CF patients-61% to 100%, depending on age and serotype-had protective levels of pneumococcal antibody . There was a significant positive correlation between antibody level and age for 5 of the 6 serotypes tested . CONCLUSIONS: In contradistinction to our hypothesis, the majority of CF patients have protective preimmunization anti-pneumococcal antibody levels . However, a significant proportion-between 17% and 39%, depending on the serotype-did not exhibit adequate levels . Therefore, we concur with current recommendations for pneumococcal immunization in CF. J Biol Chem, 2001 Nov 30, 276(48), 45168 - 74 Epub 2001 Oct 01. Tetracycline-regulated gene expression mediated by a novel chimeric repressor that recruits histone deacetylases in mammalian cells; Jiang W et al.; Regulated gene expression will provide important platforms from which gene functions can be investigated and safer means of gene therapy may be developed . Histone deacetylases have recently been shown to play an important role in regulating gene expression . Here we investigated whether a more tightly controlled expression could be achieved by using a novel chimeric repressor that recruits histone deacetylases to a tetracycline-responsive promoter . This chimeric repressor was engineered by fusing the tetracycline repressor (TetR) with an mSin3-interacting domain of human Mad1 and was shown to bind the tetO(2) element with high affinity, and its binding was efficiently abrogated by doxycycline . The chimeric repressor was shown to directly interact with mSin3 of the histone deacetylase complex . This inducible system was further simplified by using a single vector that contained both a chimeric repressor expression cassette and a tetracycline-responsive promoter . When transiently introduced into mammalian cells, the chimeric repressor system exhibited a significantly lower basal level of luciferase activity (up to 25-fold) than that of the TetR control . When stably transfected into HEK 293 cells, the chimeric repressor system was shown to exert a tight control of green fluorescent protein expression in a doxycycline dose- and time-dependent fashion . Therefore, this novel chimeric repressor provides an effective means for more tightly regulated gene expression, and the simplified inducible system may be used for a broad range of basic and clinical studies. Intern Med, 2001 Sep, 40(9), 883 - 6 Interstitial pneumonia accompanying ulcerative colitis; Chikano S et al.; We report a patient with ulcerative colitis complicated with idiopatic interstitial pneumonia, in whom the etiology of interstitial pneumonia was unknown, but immunological disturbance might have been involved . There are many complications with ulcerative colitis, but interstitial pneumonia is quite rare and its prognosis is quite poor . Antibiotic and steroid treatment were given under respiration supported therapy, but no response could be obtained . In the treatment of patients with ulcerative colitis, we must be mindful of interstitial pneumonia because the prognosis is quite poor. Cutis, 2001 Sep, 68(3), 223 - 6 Primary skeletal muscle lymphoma presenting as refractory cellulitis; Baddour LM et al.; The right torso of a 55-year-old woman showed diffuse skin and soft-tissue changes suggestive of cellulitis . However, several clinical and radiologic features, including the subacute and non-toxic nature of the illness and the patient's lack of response to antibiotic therapy, indicated a noninfectious etiology . Malignancy was suggested by striking changes seen on computed tomographic scanning--including extensive infiltration and enlargement of the musculature of the right shoulder girdle, the intercostal musculature, the latissimus dorsi, and the rhomboids; focal enlargement of the right paraspinal muscles; and enlargement of the psoas and the iliacus muscles and of the musculature around the hip joint . The mediastinal, hilar, and paraaortic regions showed no adenopathy . A large hypodense lesion of approximately 4.5 cm, which was seen in the caudate lobe of the liver, raised the concern of a metastatic focus of malignancy . Because of these findings, an immediate muscle biopsy was performed . Results showed a non-Hodgkin's lymphoma with a B-cell phenotype . Although primary skeletal muscle lymphoma is very uncommon in patients without human immunodeficiency virus infection, clinical presentation of refractory cellulitis, as seen in the current case, is extremely rare. J Biol Chem, 2001 Dec 14, 276(50), 47266 - 76 Epub 2001 Sep 28. Doxorubicin-induced apoptosis is associated with increased transcription of endothelial nitric-oxide synthase . Effect of antiapoptotic antioxidants and calcium; Kalivendi SV et al.; The clinical efficacy of the antitumor antibiotic drug doxorubicin (DOX) is severely limited by its dose-limiting cardiotoxicity in cancer patients . DOX-induced generation of reactive oxygen species was proposed to be a major mechanism of its cardiotoxicity . Previously, we showed that DOX undergoes a reductive activation at the reductase domain of endothelial nitric-oxide synthase (eNOS) forming the semiquinone and superoxide (Vasquez-Vivar, J., Martasek, P., Hogg, N., Masters, B . S . S., Pritchard, K . A., Jr., and Kalyanaraman, B . (1997) Biochemistry 36, 11293-11297) . In this report, we provide evidence for DOX-induced increase in eNOS transcription and protein expression in bovine aortic endothelial cells (BAEC) . We propose that DOX-induced hydrogen peroxide formation is responsible for the increased transcription of eNOS . BAEC treated with antisense eNOS oligonucleotide inhibits DOX-induced endothelial apoptosis . Treatment with antioxidants restored the levels of antiapoptotic proteins (Hsp70 and Bcl-2) in DOX-treated BAEC . DOX-induced intracellular oxidative stress, as measured by oxidation of dichlorodihydrofluorescein diacetate to dichlorofluorescein and hydroethidium to ethidium, was inhibited by antisense eNOS oligonucleotide and antioxidant treatment . Furthermore, antiapoptotic antioxidants (e.g . FeTBAP, ebselen, and alpha-phenyl-tert-butyl nitrone) inhibited DOX-induced eNOS transcription . We conclude that DOX-induced apoptosis is linked to the redox activation of DOX by eNOS. Br J Surg, 2001 Oct, 88(10), 1346 - 51 Diagnosis and management of a mediastinal leak following radical oesophagectomy; Griffin SM et al.; BACKGROUND: The aim of this study was to evaluate the diagnosis, management and outcome of mediastinal leaks following radical oesophagectomy with a stapled intrathoracic anastomosis . METHODS: Some 291 consecutive patients underwent two-phase subtotal oesophagectomy with gastric interposition for malignancy . Patients with clinical suspicion of a leak were investigated with contrast radiology and flexible upper gastrointestinal endoscopy . RESULTS: Nineteen patients (6.5 per cent) developed a proven mediastinal leak at a median of 8 (range 3-30) days following surgery . Contrast radiology and flexible upper gastrointestinal endoscopy identified that 13 patients had an isolated leak from the oesophagogastric anastomosis and two had widespread leakage secondary to gastrotomy-line dehiscence . Endoscopy revealed a further four patients with gastric necrosis in whom contrast radiology was normal . In six patients the diagnosis of leakage followed an apparently normal routine contrast examination on day 5-8 . All 13 isolated anastomotic leaks were managed non-operatively with targeted mediastinal drainage, intravenous antibiotics and antifungal therapy, nasogastric decompression and enteral nutrition; the mortality rate was 15 per cent (two of 13) . Patients with gastrotomy dehiscence or gastric necrosis had a more severe clinical picture; they were managed with repeat thoracotomy and either revision of the conduit or resection and exclusion . Despite early intervention four of the six patients died . CONCLUSION: Routine postoperative contrast radiology cannot be recommended . On clinical suspicion of a leak patients require both contrast radiology and endoscopic evaluation . Isolated anastomotic leaks can be managed successfully with non-operative treatment, whereas more extensive leaks from the gastric conduit require revisional surgery which carries a high mortality rate. No To Shinkei, 2001 Aug, 53(8), 775 - 9 {Multiple brain abscesses associated with Rendu-Osler-Weber disease: report of two cases}; Shimokawa S et al.; Two cases of multiple brain abscesses associated with congenital pulmonary arteriovenous fistula are reported . A 57-year-old male with Rendu-Osler-Weber disease complicated by pulmonary arteriovenous fistula developed multiple brain abscesses in the right parietal region . He responded well to surgical drainage and antibiotic therapy, and the pulmonary arteriovenous fistula, located in the left lower lobe, was resected . A 26-year-old female with Rendu-Osler-Weber disease complicated by pulmonary arterivenous fistula developed recurrent multiple brain abscesses in both the frontal and right parietal regions . The brain abscesses were successfully treated with aspiration and antibiotic therapy . She had a history of two previous brain abscesses in the right parietal regions that were excised on separate occasions at 16 and 23 years of age . Although pulmonary arteriovenous fistula was confirmed by angiography, in this case surgical removal of the pulmonary lesions was not indicated due to multiple vascular shunting . The patient had no recurrence of brain abscess with oral antibiotic therapy. Klin Padiatr, 2001 Sep, 213 Suppl 1, A88 - 102 {Hematopoietic growth factors in the prevention of infections complications in children with hematologic-oncologic diseases}; Lehrnbecher T; The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce, but not eliminate infectious complications associated with therapy-induced neutropenia . Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications . In the course of evaluating the multitude of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors . To prevent serious infection, the use of G- or GM-CSF is recommended in a subset of pediatric cancer patients shortly after receiving chemotherapy or a marrow transplant . Children with intensive chemotherapy (e.g., children with high risk ALL, NHL or metastatic neuroblastoma) seem to benefit from hematopoietic growth factors whereas it is not clear that this applies to children undergoing therapy for solid tumors such as rhabdomyosarcoma or Ewing's sarcoma . An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells . Future studies in pediatric cancer patients are clearly warranted to address several issues . Prospective clinical trials are still needed to define specific treatment groups who can benefit from growth factor support . In this regard, efforts must be directed at better defining the endpoints and in particular, assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs . In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups, depending upon underlying malignancy and therapy given . In addition, combinations of different growth factors have to be tested, particularly if ex vivo expansion and the storage of hematopoietic stem cells are to be utilized in a wider spectrum of patients. Klin Padiatr, 2001 Sep, 213 Suppl 1, A9 - A21 {Non-pharmacologic strategies to prevent and control infectious complications in pediatric hematology/oncology patients}; Simon A et al.; Preventive strategies besides the use of prophylactic antibiotic or antifungal regimens are fundamental ingredients of infection control in pediatric hematology-oncology patients . The clinical spectrum and the routes of transmission of infectious diseases in children have to be considered and preventive strategies should be adjusted to host dependent risk factors, in particular to the degree and duration of severe immunosuppression (i.e . neutropenia) . This article overviews practical guidelines to prevent exposure and to reduce external sources of infection in immunocompromised children . Scientific evidence from controlled randomized studies is lacking or incomplete for many of these measures . A systematic and pragmatic approach to the critical control points of patient care in pediatric hematology/oncology is prudent to solve this problem in clinical practice . The corresponding recommendations are categorized in IV different levels of evidence. Microbiology, 2001 Oct, 147(Pt 10), 2817 - 29 The gene cluster for chloramphenicol biosynthesis in Streptomyces venezuelae ISP5230 includes novel shikimate pathway homologues and a monomodular non-ribosomal peptide synthetase gene; He J et al.; Regions of the Streptomyces venezuelae ISP5230 chromosome flanking pabAB, an amino-deoxychorismate synthase gene needed for chloramphenicol (Cm) production, were examined for involvement in biosynthesis of the antibiotic . Three of four ORFs in the sequence downstream of pabAB resembled genes involved in the shikimate pathway . BLASTX searches of GenBank showed that the deduced amino acid sequences of ORF3 and ORF4 were similar to proteins encoded by monofunctional genes for chorismate mutase and prephenate dehydrogenase, respectively, while the sequence of the ORF5 product resembled deoxy-arabino-heptulosonate-7-phosphate (DAHP) synthase, the enzyme that initiates the shikimate pathway . A relationship to Cm biosynthesis was indicated by sequence similarities between the ORF6 product and membrane proteins associated with Cm export . BLASTX searches of GenBank for matches with the translated sequence of ORF1 in chromosomal DNA immediately upstream of pabAB did not detect products relevant to Cm biosynthesis . However, the presence of Cm biosynthesis genes in a 7.5 kb segment of the chromosome beyond ORF1 was inferred when conjugal transfer of the DNA into a blocked S . venezuelae mutant restored Cm production . Deletions in the 7.5 kb segment of the wild-type chromosome eliminated Cm production, confirming the presence of Cm biosynthesis genes in this region . Sequencing and analysis located five ORFs, one of which (ORF8) was deduced from BLAST searches of GenBank, and from characteristic motifs detected in alignments of its deduced amino acid sequence, to be a monomodular nonribosomal peptide synthetase . GenBank searches did not identify ORF7, but matched the translated sequences of ORFs 9, 10 and 11 with short-chain ketoreductases, the ATP-binding cassettes of ABC transporters, and coenzyme A ligases, respectively . As has been shown for ORF2, disrupting ORF3, ORF7, ORF8 or ORF9 blocked Cm production. Biomaterials, 2001 Nov, 22(22), 3067 - 72 In vitro study of the effect of titanium on porphyromonas gingivalis in the presence of metronidazole and spiramycin; Bunetel L et al.; Septic peri-implantitis is the main clinical complication encountered following the insertion of titanium implants . It may be resistant to conventional antibiotic treatments . Reports in the literature about antibiotic behavior in the presence of titanium remain controversial . They vary from a bacteriostat to a decreased effect of antibiotic . This study examined, in vitro, the viability of Porphyromonas gingivalis, frequently associated with periodontal diseases, in the presence of titanium and antibiotics (spiramycin and metronidazole alone or in combination) . Viability of P . gingivalis was determined, versus a standard curve using the Live/dead Baclight Bacteria Viability Kit on 96 well microplates . The results of 48 experiments (60 measurements each) were compiled in a database and compared to each other using the chi2p < 0.05 test . When used alone, titanium enhanced bacterial growth as the nickel-chrome control . However, when titanium was used in the presence of antibiotics, antibiotics kept their own effects . Even more, titanium was shown to potentialize the effect of metronidazole . The strengthening of effectiveness of metronidazole by titanium may be due to the oxidation potential of the metal . This chemical property could explain the conflicting data reported in the literature. Ann Emerg Med, 2001 Oct, 38(4), 357 - 63 An emergency department-based randomized trial of nonbronchoscopic bronchoalveolar lavage for early pathogen identification in severe community-acquired pneumonia; Rodriguez RM et al.; STUDY OBJECTIVES: Many patients with community-acquired pneumonia are treated empirically without an aggressive search for causative pathogens, an approach adopted largely because of the costs and difficulties encountered during efforts to identify the causative organisms . Blood and sputum cultures are not sensitive, and the more invasive techniques of bronchoscopy and lung biopsy are generally time consuming and not cost-effective . The technique of nonbronchoscopic bronchoalveolar lavage (BAL) has been shown to accurately diagnose the causes of nosocomial pneumonia . The purpose of this study was to determine whether an emergency department-based BAL protocol would lead to more frequent isolation of pneumonia pathogens and result in more changes to tailored antibiotic therapy in comparison with standard care . METHODS: We studied all adult patients admitted with a diagnosis of pneumonia who were tracheally intubated and who had obtainable familial consent in the ED of an urban county hospital from March 1998 to October 1999 . Exclusions included antibiotic use within the past 5 days, pneumothorax, hemoptysis, or persistent hypoxia using 100% oxygen . Patients were randomized to standard care versus standard care plus BAL . Blood culture specimens were drawn from all patients before the initiation of antibiotics . All other diagnostic tests were ordered at the discretion of treating physicians . BAL fluid, sputum, and blood culture specimens were tracked, and patient antibiotic course was followed to assess any change in regimen . RESULTS: Twenty-six of 64 patients evaluated for study participation met all eligibility criteria; 14 patients received standard care, and 12 patients received standard care plus BAL . Pneumonia pathogens were identified in 10 (83.3%) of 12 patients in the BAL group and in 4 (28.6%) of 14 patients in the standard care group (P =.007) . Comparing BAL versus non-BAL groups, there was no significant difference in the likelihood of overall antibiotic regimen changes (P =.149), but there was a difference with regard to antibiotic changes made in patients with positive culture test results (P =.026) . No major complications occurred with BAL catheterizations . CONCLUSION: ED-based BAL catheterization allows for early identification of pathogens in severe community-acquired pneumonia, which leads to changes in antibiotic therapy. Am J Public Health, 2001 Oct, 91(10), 1617 - 24 Community health worker performance in the management of multiple childhood illnesses: Siaya District, Kenya, 1997-2001; Kelly JM et al.; OBJECTIVES: To characterize community health worker (CHW) performance using an algorithm for managing common childhood illnesses in Siaya District, Kenya, we conducted CHW evaluations in 1998, 1999, and 2001 . METHODS: Randomly selected CHWs were observed managing sick outpatient and inpatient children at a hospital, and their management was compared with that of an expert clinician who used the algorithm . RESULTS: One hundred, 108, and 114 CHWs participated in the evaluations in 1998, 1999, and 2001, respectively . The proportions of children treated "adequately" (with an antibiotic, antimalarial, oral rehydration solution, or referral, depending on the child's disease classifications) were 57.8%, 35.5%, and 38.9%, respectively, for children with a severe classification and 27.7%, 77.3%, and 74.3%, respectively, for children with a moderate (but not severe) classification . CHWs adequately treated 90.5% of malaria cases (the most commonly encountered classification) . CHWs often made mistakes assessing symptoms, classifying illnesses, and prescribing correct doses of medications . CONCLUSIONS: Deficiencies were found in the management of sick children by CHWs, although care was not consistently poor . Key reasons for the deficiencies appear to be guideline complexity and inadequate clinical supervision; other possible causes are discussed. Org Lett, 2001 Oct 4, 3(20), 3157 - 9 Enantioselective synthesis of (2-pyridyl)alanines via catalytic hydrogenation and application to the synthesis of L-azatyrosine; Adamczyk M et al.; {reaction: see text} A novel method for the synthesis of (2-pyridyl)alanines 2a-b was developed by converting (2-pyridyl)dehydroamino acid derivatives 1a-b to the corresponding N-oxides 3a-b followed by asymmetric hydrogenation using (R,R)-{Rh(Et-DUPHOS)(COD)}BF(4) {(R,R)-6} catalyst and subsequent N-oxide reduction in 80-83% ee . This methodology was applied to the total synthesis of L-azatyrosine {(+)-12}, an antitumor antibiotic, starting from (5-benzyloxy)-2-pyridylmethanol (7), in >96% enantiomeric purity. J Dairy Sci, 2001 Sep, 84(9), 1959 - 68 Impact of CO2 addition to milk on selected analytical testing methods; Ma Y et al.; The addition of CO2 to raw milk and dairy products controls the growth of psychrotrophic bacteria at refrigeration temperatures . The objective of this study was to determine the effects of dissolved CO2 in milk on the performance of four important routine testing methods: antibiotic residue test, freezing point test, infrared milk component analysis, and alkaline phosphatase test . Raw or pasteurized whole milk was carbonated at <4 degrees C to contain approximately 0 (control), 200, 400, 600, and 1000 ppm of CO2 . The addition of CO2 to raw milk up to 1000 ppm had no effect on the performance of the three antibiotic (beta-lactams) residue tests: IDEXX SNAP, Charm II Sequential Tablet, and Delvo-P Ampule . Milk freezing point decreased linearly with increasing concentration of dissolved CO2, from -0.543 degrees H (control) to -0.595 degrees H (1000 ppm) . Carbonation to 1000 ppm decreased milk pH (measured at 38 degrees C) from 6.61 (control) to 6.15 (1000 ppm) . The effects of CO2 on milk freezing point and pH were reversible upon removal of dissolved CO2 . Increased CO2 levels in milk changed the infrared absorption spectrum of milk and caused the corrected lactose readings to decrease and the corrected fat B readings to increase . For the alkaline phosphatase tests, 0 (none), 0.05, 0.1, and 0.2% raw milk were deliberately added to pasteurized milks of six levels of carbonation (0 to 1000 ppm) . The addition of CO2 did not influence the ability of Fluorophos, Charm PasLite, and Scharer Modified Rapid tests to differentiate between a pasteurized milk and a pasteurized milk with raw milk contamination. Ned Tijdschr Geneeskd, 2001 Sep 8, 145(36), 1713 - 6 {Sinusitis as a major cause of fever in intubated patients}; Vonk Noordegraaf A et al.; Because sinusitis is usually clinically silent in intubated patients, it is not widely appreciated as an important source of infection and fever in critically ill patients . Three such patients, two men aged 22 and 36 years, and a woman aged 50 years, suffered from respiratory insufficiency due to pneumonia . The course of the disease was determined by the sinusitis, which did not resolve during antibiotic therapy of the pneumonia, notwithstanding the fact that the causative micro-organism was susceptible to the antibiotics administered, and that both the tracheal and gastric tubes were led through the mouth instead of the nose . Flushing of the sinuses caused the fever to disappear and led to recovery of the patients . An aggressive approach to diagnose sinusitis in the intubated patient with fever in the intensive care unit is needed . A maxillary sinus lavage and culture, followed by treatment with specific antibiotics should be an integral part of the diagnosis and treatment in these patients . Surgery is indicated in the event of persistent sepsis. Wien Klin Wochenschr, 2001 Aug 16, 113(15-16), 605 - 9 {Therapy of neurotrophic keratopathy in trigeminal schwannoma with radiosurgery}; Ardjomand N et al.; BACKGROUND: We present a patient with neurotrophic keratopathy due to a trigeminal nerve neurinoma, who was successfully treated by radiosurgery . PATIENT: A patient was referred to us with recurrent corneal erosions of unknown origin in his left eye . In addition, he suffered from mild hypoesthesia in the distribution of the first branch of the trigeminal nerve . He was started on topical lubricants (hyaluronic acid 0.5%) and antibiotic ointments (gentamycin), but since no corneal healing occurred, a soft contact lens was applied . The patient developed severe corneal neovascularization within four weeks and the contact lens had to be removed . Three months later an MRI scan was performed, which showed an intracranial tumor originating from the first branch of the trigeminal nerve . Neurinoma of the trigeminal nerve was suspected, and this presumed diagnosis was confirmed by fine needle biopsy . The patient underwent radiosurgery seven weeks later . The epithelium closed, the cornea recovered and stayed stable until the last examination 18 months after radiosurgery . CONCLUSION: Radiosurgery is a promising alternative to conventional microsurgery in cases of neurinomas of the trigeminal nerve including neurotrophic keratopathy, to keep or restore vision. J Ind Microbiol Biotechnol, 2001 Jun, 26(6), 341 - 4 Induction of microcin B17 formation in Escherichia coli ZK650 by limitation of oxygen and glucose is independent of glucose consumption rate; Gao Q et al.; We examined the consumption of glucose from the media in which Escherichia coli ZK650 was grown . This organism, which produces the polypeptide antibiotic microcin B17 best under conditions of limiting supplies of glucose and air, was grown with a low level of glucose (0.5 mg/ml) as well as a high level (5.0 mg/ml) under both high and low aeration . Glucose consumption rates were virtually identical under both high and low aeration . Thus, glucose consumption rate is not a regulating factor in microcin B17 formation. Curr Opin Crit Care, 2001 Aug, 7(4), 263 - 7 Serious intra-abdominal infections; Barie PS; Serious intra-abdominal infections continue to plague patients and vex surgeons and other caregivers . The mortality rate can exceed 20%, and the morbidity associated with severe cases (eg, enterocutaneous fistula, ventral hernia resulting from open-abdomen management) requires reoperation and months of convalescence . There is no consensus as to the definition of severity and a paucity of studies that focus on treatment at the severe end of the spectrum . Attempts are being made to address the adequacy of operative management (adequacy of "source control") in the context of randomized antibiotic trials . The surgical procedure is the primary treatment modality for most types of intra-abdominal infection, whereas antibiotic therapy is usually adjunctive . It remains to be determined whether the adequacy of source control can be quantified meaningfully. Arch Intern Med, 2001 Sep 24, 161(17), 2099 - 104 Processes of care, illness severity, and outcomes in the management of community-acquired pneumonia at academic hospitals; Dedier J et al.; BACKGROUND: Prompt antibiotic administration, oxygenation measurement, and blood cultures are generally considered markers of high-quality care in the inpatient management of community-acquired pneumonia (CAP) . However, few studies have examined the relationship between prompt achievement of process-of-care markers and outcomes for patients with CAP . We examined whether antibiotic administration within 8 hours of hospital arrival, a blood culture within 24 hours, an oxygenation measurement within 24 hours, or performing blood cultures before giving antibiotics was associated with the following: (1) reaching clinical stability within 48 hours of hospital admission, (2) a decreased length of hospital stay, or (3) fewer inpatient deaths . METHODS: A retrospective medical record review identified 1062 eligible patients discharged from the hospital with a diagnosis of CAP between December 1, 1997, and February 28, 1998, among 38 US academic hospitals . We assessed the independent relationship between each process marker and the 3 clinical outcomes, controlling for the Pneumonia Severity Index on admission . We also examined the relationship of pneumonia severity on admission to process marker achievement and clinical outcomes . RESULTS: Overall, there was no consistent or statistically significant relationship between achieving process markers and better clinical outcomes (P>.40 for all) . We did observe that performing blood cultures within 24 hours was related to not achieving clinical stability within 48 hours (odds ratio, 1.62; 95% confidence interval, 1.13-2.33) . However, this finding likely reflects residual confounding by severity of illness, since increasing pneumonia severity on admission was associated with blood culture performance (P =.009) and with shorter times to antibiotic administration (P =.04) . CONCLUSIONS: Achieving process-of-care markers was not associated with improved outcomes, but was related to the severity of pneumonia as assessed on admission . Our results highlight the difficulty in demonstrating a link between process-of-care markers and outcomes in observational studies of CAP . Randomized studies are needed to objectively evaluate the impact of process-of-care markers on CAP outcomes. Biochemistry, 2001 Oct 2, 40(39), 11676 - 86 Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles; Townsley LE et al.; Gramicidins A, B, and C are the three most abundant, naturally occurring analogues of this family of channel-forming antibiotic . GB and GC differ from the parent pentadecapeptide, GA, by single residue mutations, W11F and W11Y, respectively . Although these mutations occur in the cation binding region of the channel, they do not affect monovalent cation specificity, but are known to alter cation-binding affinities, thermodynamic parameters of cation binding, conductance and the activation energy for ion transport . The structures of all three analogues incorporated into deuterated sodium dodecyl sulfate micelles have been obtained using solution state 2D-NMR spectroscopy and molecular modeling . For the first time, a rigorous comparison of the 3D structures of these analogues reveals that the amino acid substitutions do not have a significant effect on backbone conformation, thus eliminating channel differences as the cause of variations in transport properties . Variable positions of methyl groups in valine and leucine residues have been linked to molecular motions and are not likely to affect ion flow through the channel . Thus, it is concluded that changes in the magnitude and orientation of the dipole moment at residue 11 are responsible for altering monovalent cation transport. Infect Dis Clin North Am, 2001 Sep, 15(3), 775 - 96 Surgical infections in patients with chronic renal failure; Cheung AH et al.; Patients with chronic renal failure and uremia have impaired host defenses and wound healing that can lead to an increased risk of infection in addition to a frequent need for surgical procedures with synthetic grafts and catheters . Antibiotic therapy plus timely surgical intervention in removal of infected grafts and catheters is crucial for infection control and patient survival . Other surgical infections, such as wound problems, intraabdominal infections, fungal infections, diabetic foot ulcers, and necrotizing soft tissue infections must be attended to promptly. Arch Pediatr Adolesc Med, 2001 Sep, 155(9), 1017 - 21 Exposures and outcomes of children with urticaria seen in a pediatric practice-based research network: a case-control study; Plumb J et al.; OBJECTIVES: (1) To determine the duration, outcome, and associated findings of urticaria in children seen by general pediatricians; (2) to compare the exposure to foods, medications, insect stings or bites, and the presence of other symptoms in children with urticaria with controls; (3) to determine general pediatricians' management of urticaria . DESIGN: Case-control . PARTICIPANTS: Children with urticaria seen by Utah Pediatric Practice Based Research Network members between August 1, 1999, and August 31, 2000 . Control patients were matched for age and sex . MAIN OUTCOME MEASURES: Duration of urticaria; associated symptoms; personal and family history of atopy; medications; ingestion of peanuts, nuts, shellfish, tomatoes, strawberries, or eggs; being stung by an insect; suspected cause, diagnostic studies; treatment . RESULTS: Fifty-two cases and 47 controls were enrolled . The mean duration of urticaria was 8.9 days (range, 1-50 days) . Seventeen patients (33%) and 1 control patient were taking antibiotics (odds ratio {OR}, 22.3; 95% confidence interval {CI}, 2.8-176; chi(2), P<.001) . Fourteen patients and 5 controls had gastrointestinal symptoms (OR, 3.1; 95% CI, 1.02-9.4; chi(2), P =.04) . There were no differences between cases and controls for other symptoms, personal or family history of atopy, ingestion of the foods listed, insect sting, or other medications . A cause was suspected in 28 patients (54%): a "viral illness" (19%), antibiotics (15%), or a combination (35%) . CONCLUSIONS: Patients were more likely than controls to be taking an antibiotic and were more likely to have a personal or family history of atopy or to report ingesting foods commonly associated with urticaria . A viral illness was the most common cause suspected by pediatricians. J Bacteriol, 2001 Oct, 183(20), 5982 - 90 Escherichia coli FadR positively regulates transcription of the fabB fatty acid biosynthetic gene; Campbell JW et al.; In Escherichia coli expression of the genes of fatty acid degradation (fad) is negatively regulated at the transcriptional level by FadR protein . In contrast the unsaturated fatty acid biosynthetic gene, fabA, is positively regulated by FadR . We report that fabB, a second unsaturated fatty acid biosynthetic gene, is also positively regulated by FadR . Genomic array studies that compared global transcriptional differences between wild-type and fadR-null mutant strains, as well as in cultures of each strain grown in the presence of exogenous oleic acid, indicated that expression of fabB was regulated in a manner very similar to that of fabA expression . A series of genetic and biochemical tests confirmed these observations . Strains containing both fabB and fadR mutant alleles were constructed and shown to exhibit synthetic lethal phenotypes, similar to those observed in fabA fadR mutants . A fadR strain was hypersensitive to cerulenin, an antibiotic that at low concentrations specifically targets the FabB protein . A transcriptional fusion of chloramphenicol acetyltransferase (CAT) to the fabB promoter produces lower levels of CAT protein in a strain lacking functional FadR . The ability of a putative FadR binding site within the fabB promoter to form a complex with purified FadR protein was determined by a gel mobility shift assay . These experiments demonstrate that expression of fabB is positively regulated by FadR. Biochim Biophys Acta, 2001 Sep 21, 1520(3), 223 - 33 Phenotypic characterization of a comprehensive set of bicyclomycin-resistant mutants; Moyse KA et al.; A comprehensive set of bicyclomycin-resistant mutants of transcription termination protein Rho has been characterized in Escherichia coli by in vivo and in vitro assays . Several of the mutant Rho proteins have functional defects . Strains with either the L208R or the S266A mutation in the bacterial chromosome have a higher intracellular concentration of the Rho protein than strains containing a wild-type copy of the rho gene . Strains carrying the L187R, L208R or S266A mutations in the chromosome also have a mutant phenotype; a plasmid-located arabinose promoter is constitutively de-repressed in these strains . The L208R and S266A mutant strains also have a rate of growth defect . When the S266A mutation is located on a high-copy plasmid, the mutant grows more slowly than a wild-type strain . In contrast to the majority of the bicyclomycin-resistant mutants, these two mutants show clear phenotypic differences from wild-type cells . These differences are also seen in vitro . In vitro transcription termination by RhoL208R and RhoS266A is defective at the lambda tR1 terminator, but can be enhanced by NusG . These functionally defective Rho mutations have been located near the putative catalytic site on a model of Rho based on the F1-ATPase . This indicates that this region of the Rho molecule is crucial for Rho function . The crucial region overlaps the putative bicyclomycin-binding site, suggesting an explanation for the efficacy of bicyclomycin as an antibiotic. Haemophilia, 2001 Jul, 7 Suppl 2, 26 - 30 Chemical synoviorthesis with rifampicin in haemophilia; Caviglia HA et al.; Rifampicin is an antibiotic that has been currently used for the treatment of noninfectious articular lesions with satisfactory results . The first experience was performed with patients who presented rheumatoid arthritis, and later with haemophilic patients . The clinical experience of three haemophilia centres which used rifampicin for the treatment of chronic haemophilic synovitis is presented here . The protocols were different . It was observed that rifampicin is more effective when it is used in small joints (elbows and ankles), than when used in bigger ones (knees), and that a high number of injections predicts failure . Mention is also made of experimental studies in animals where it was shown that the healing pattern of rifampicin is similar to that of NSAIDs. Clin Oral Implants Res, 2001 Oct, 12(5), 468 - 72 Effect of total body irradiation on peri-implant tissue reaction: an experimental study; Renou SJ et al.; The aim of the present study was to evaluate the osseointegration process under total body irradiation conditions (LD 50/30) . Twenty Wistar rats (mean body weight: 90 g) were used . Under ethyl urethane intraperitoneal anesthesia (1 g/kg body weight), the animals were irradiated with a single 700 cGy dose (linear accelerator 6 Mev photons) . Four days post irradiation, a titanium laminar implant was placed in the left tibia of each rat . Antibiotic therapy (ceftriaxone) was administered daily post implantation, to prevent infection by radiation . Fourteen days post implantation, the animals were killed by ether overdose . The tibiae were resected, radiographed and processed for embedding in methyl methacrylate . The results showed impaired osteogenesis and absence of osseointegration in experimental tibiae . This could be due to a direct action of total body irradiation on osteogenesis precursor cells . This effect would impair bone formation involved in peri-implant osseointegration processes in this experimental model. J S Afr Vet Assoc, 2001 Mar, 72(1), 49 - 51 Cervical teratoma in a dog; Lambrechts NE et al.; A young adult boxer dog was examined for a painless swelling in the left cranial cervical area that was refractory to antibiotic therapy . Ultrasound examination revealed a hypoechoic mass abutting the rostrolateral aspect of the left mandibular salivary gland . The cystic mass was excised and was found to extend through the capsule of the salivary gland and appeared to be confluent with the glandular tissue at this point . Histopathological examination of the excised tissue demonstrated tissue from all 3 germinal layers . There was no indication of malignancy and the mass was diagnosed as a benign cervical teratoma . Hypotheses regarding the origin of teratomas in general are discussed and the origin of the teratoma in this case is suggested. Indian J Biochem Biophys, 2001 Feb-Apr, 38(1-2), 71 - 4 Interaction of mithramycin with chromatin; Mir MA et al.; Mithramycin (MTR) is an anti-cancer antibiotic that blocks the macromolecular biosynthesis via reversible interaction with DNA template in the presence of bivalent metal ion such as Mg2+ . In absence of DNA, mithramycin forms two types of complexes with Mg2+, complex I (with 1:1 stoichiometry in terms of MTR: Mg2+) and complex II (with 1:2 stoichiometry in terms of MTR: Mg2+) . In an eukaryotic system, the drug would interact with chromatin, a protein-DNA complex . We have employed the spectroscopic techniques such as absorption and fluorescence to study the interaction of MTR: Mg2+ complexes with rat liver chromatin . In this report, we have shown that the two types of ligands have different binding potentials with the same chromatin . This supports our proposition that complexes I and II, are different molecular species . We have also shown that the histone protein(s) reduce the binding potential and the number of available sites for both ligands. Mem Inst Oswaldo Cruz, 2001 Aug, 96(6), 831 - 3 Polygodial, the fungitoxic component from the Brazilian medicinal plant Polygonum punctatum; de Almeida Alves TM et al.; Polygonum punctatum (Polygonaceae) is an herb known in some regions of Brazil as "erva-de-bicho" and is used to treat intestinal disorders . The dichloromethane extract of the aerial parts of this plant showed strong activity in a bioautographic assay with the fungus Cladosporium sphaerospermum . The bioassay-guided chemical fractionation of this extract afforded the sesquiterpene dialdehyde polygodial as the active constituent . The presence of this compound with antibiotic, anti-inflammatory and anti-hyperalgesic properties in "erva-de-bicho" may account for the effects attributed by folk medicine to this plant species. J Manipulative Physiol Ther, 2001 Sep, 24(7), 474 - 6 Acute lymphangitis mimicking mechanical neck pain; Boudreau LA et al.; OBJECTIVE: To discuss acute lymphangitis as a potentially serious infection that can mimic mechanical musculoskeletal pain . CLINICAL FEATURES: A 27-year-old male plant worker had right-sided neck pain . Numerous lesions on the patient's scalp were observed, but were not considered to be related to the chief complaint . INTERVENTION AND OUTCOME: Conservative therapy was initiated to address what was thought to be mechanical neck pain . Shortly after the initial visit, it became evident that the source of the neck pain was infection because lymphangitis developed . Antibiotic therapy was initiated and complete resolution of the complaint occurred within 1 week . CONCLUSION: Primary contact practitioners should consider all aspects of the patient history and physical findings when formulating a diagnosis . This is especially important in the case of patients presenting with lymphangitis because mismanagement could have serious consequences . The importance of a good patient history and team approach to care is demonstrated by this case. J Orthop Res, 2001 Sep, 19(5), 950 - 4 Toxic effect of rifampicin on human osteoblast-like cells; Isefuku S et al.; We examined the effects of rifampicin on osteoblast-like cells derived from adult human bone in vitro . Cancellous bone was collected from five different individuals during elective orthopaedic operations and cultured in antibiotic-free media . Total DNA, 3H-thymidine incorporation and alkaline phosphatase (ALP) activity were measured after the cells were cultured for 4 days in media containing concentrations of rifampicin ranging from 0 to 1000 microg/ml . Mean total DNA was decreased at concentrations of 10 microg/ml and above in the cultures obtained from four out of five individuals but these decreases were significant in the cultures from only two individuals . 3H-thymidine incorporation, a more sensitive indicator of change in cell proliferation, and ALP activity were significantly decreased (P < 0.05) in all of the cultures containing 3 and 7 microg/ml, respectively . In the clinical setting, serum concentrations of rifampicin often exceed 10 microg/ml after systemic administration . The present study has shown that rifampicin, at these concentrations, can inhibit the proliferation of osteoblast-like cells in vitro . Further studies should be carried out to assess whether rifampicin is detrimental to the bone repair process in vivo. Comp Immunol Microbiol Infect Dis, 2001 Oct, 24(4), 217 - 31 Therapeutic effect of anti-TNF-alpha antibody and levofloxacin (LVFX) in a mouse model of enterohemorrhagic Escherichia coli O157 infection; Isogai E et al.; The ability of an anti-TNF-alpha antibody to confer protection against enterohaemorrhagic Escherichia coli (EHEC) O157 was investigated in germfree IQI mice . The use of an antibiotic levofloxacin (LVFX) alone or with the antibody was also studied . Protection included an increase in survival rate . Treatment with the anti-TNF-alpha antibody inhibited the histological signs associated with EHEC infection but did not prevent the colonization of EHEC or production of Shiga toxin (Stx) . No clinical signs were observed and EHEC was completely eliminated in the mouse model receiving both anti-TNF-alpha antibody and LVFX . Anti-TNF-alpha antibody suppressed inflammatory cytokine response in the mouse kidney and brain by EHEC infection. J Pharmacol Exp Ther, 2001 Oct, 299(1), 351 - 7 Flavonoids with epidermal growth factor-receptor tyrosine kinase inhibitory activity stimulate PEPT1-mediated cefixime uptake into human intestinal epithelial cells; Wenzel U et al.; We have tested 33 flavonoids, occurring ubiquitously in foods of plant origin, for their ability to alter the transport of the beta-lactam antibiotic cefixime via the H+-coupled intestinal peptide transporter PEPT1 in the human intestinal epithelial cell line Caco-2 . Of the flavonoids tested, quercetin, genistein, naringin, diosmin, acacetin, and chrysin increased uptake of {14C}cefixime dose dependently by up to 60% . All other flavonoids were either without effect or decreased the absorption of cefixime . Quercetin was shown to increase the Vmax of cefixime influx without changing the apparent Km for transport . However, the expected concomitant increase in intracellular acidification due to PEPT1-mediated cefixime/H+-cotransport was less pronounced in the presence of quercetin . This suggested that pH regulatory systems such as apical Na+/H+-exchange could be activated by quercetin and maintain the proton-motive driving force for cefixime uptake . Since quercetin and genistein have been shown to inhibit epidermal growth factor (EGF)-receptor tyrosine kinases, we applied tyrphostin 25 to prove whether such an inhibition could explain the stimulatory effects seen on cefixime uptake . It was found that tyrphostin 25 simulated the effects of quercetin by increasing cefixime absorption due to maintenance of the transmembrane pH gradient . In conclusion, our studies show that flavonoids with EGF-receptor tyrosine kinase inhibitory activities enhance the intestinal absorption of the beta-lactam antibiotic cefixime in Caco-2 cells by activation of apical Na+/H+-exchange and a co