Antibiotics

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 concomitant increase of the driving force for PEPT1.

Genetics, 2001 Sep, 159(1), 241 - 54
Technical knockout, a Drosophila model of mitochondrial deafness; Toivonen JM et al.; Mutations in mtDNA-encoded components of the mitochondrial translational apparatus are associated with diverse pathological states in humans, notably sensorineural deafness . To develop animal models of such disorders, we have manipulated the nuclear gene for mitochondrial ribosomal protein S12 in Drosophila (technical knockout, tko) . The prototypic mutant tko(25t) exhibits developmental delay, bang sensitivity, impaired male courtship, and defective response to sound . On the basis of a transgenic reversion test, these phenotypes are attributable to a single substitution (L85H) at a conserved residue of the tko protein . The mutant is hypersensitive to doxycyclin, an antibiotic that selectively inhibits mitochondrial protein synthesis, and mutant larvae have greatly diminished activities of mitochondrial redox enzymes and decreased levels of mitochondrial small-subunit rRNA . A second mutation in the tko gene, Q116K, which is predicted to impair the accuracy of mitochondrial translation, results in the completely different phenotype of recessive female sterility, based on three independent transgenic insertions . We infer that the tko(25t) mutant provides a model of mitochondrial hearing impairment resulting from a quantitative deficiency of mitochondrial translational capacity.

Br J Clin Pharmacol, 2001 Sep, 52(3), 319 - 21
Preferential prescribing of oral corticosteroids in Irish male asthmatic children; Williams D et al.; AIMS: To determine if there is a gender difference in the prescription of oral corticosteroids in asthmatic children (< 15 years) . METHODS: 8072 asthmatics were identified on the basis that they received a prescription for either an inhaled beta-adrenoceptor agonist, an inhaled corticosteroid, inhaled cromoglycate/nedocromil sodium, oral xanthines or leukotriene antagonist . Odds ratios (OR) and 95% confidence intervals (CI) were determined for the different asthma treatments for males compared with females . RESULTS AND CONCLUSIONS: Male asthmatic children were more likely (OR = 1.37, 95% CI = 1.21,1.55, P < 0.001) to receive a prescription for an oral corticosteroid compared with their female counterparts suggesting a possible increased severity of their condition, rather than a different management of their disease . Male asthmatic children were less likely to be prescribed an antibiotic over the study period (OR = 0.85, 95% CI = 0.77, 0.93, P < 0.001).

Cancer Res, 2001 Sep 15, 61(18), 6816 - 21
Taurolidine: cytotoxic and mechanistic evaluation of a novel antineoplastic agent; Calabresi P et al.; Bis-(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)methane (taurolidine) is a synthetic broad-spectrum antibiotic that reacts with bacterial cell membrane components to prevent adhesion to epithelial cell surfaces . Reflecting the key role of adhesion in the growth and development of human solid tumors, studies were initiated to assess the antiproliferative activity of this agent in selected human and murine tumor cell lines . A 3-day exposure to Taurolidine inhibited the growth of all of the cell lines evaluated with IC(50)s ranging from 9.6-34.2 microM . Studies to identify the mechanism responsible for this effect were conducted in NIH-3T3 murine fibroblasts and the PA-1 and SKOV-3 human ovarian tumor cells . These studies revealed that a 48-h exposure to taurolidine had little effect on cell cycle distribution in PA-1 and SKOV-3 cells but significantly increased the appearance of DNA debris in the sub-G(0)/G(1) region, an effect consistent with an induction of apoptosis . In contrast, in NIH-3T3 cells, taurolidine exposure did not increase DNA debris in the sub-G(0)/G(1) region . Additional studies assessed phosphotidylserine externalization after a 24-h exposure to taurolidine using annexin-V binding as a cell surface marker . These studies revealed that taurolidine increased the percentage of annexin-V-positive cells by 4-fold and 3-fold in PA-1 and SKOV-3 cells, respectively . In NIH-3T3 cells, taurolidine exposure slightly increased ( approximately 5%) annexin-V binding . Parallel studies revealed that exposure to taurolidine also resulted in poly(ADP-ribose) polymerase cleavage in both ovarian tumor cell lines but not in NIH-3T3 cells . Finally, murine-based studies were conducted to assess the antineoplastic activity of three consecutive daily i.p . bolus injections of taurolidine at doses ranging from 5-mg injection/mouse to 30-mg injection/mouse . The 20-mg injection dose produced approximately 10% mortality and was identified as the maximally tolerated dose in this model . Administration of this regimen to nude mice bearing i.p . human ovarian tumor xenografts significantly inhibited both tumor formation and growth . These findings are discussed in light of their clinical implications.

Clin Ther, 2001 Aug, 23(8), 1281 - 91
A randomized, double-blind comparison of ampicillin/sulbactam and ceftriaxone in the prevention of surgical-site infections after neurosurgery; Zhu XL et al.; BACKGROUND: The use of prophylactic antibiotics has been shown to decrease the rate of surgical-site infections after clean neurosurgical operations, although previous clinical trials have provided no evidence that one antibiotic is superior to another for this purpose . OBJECTIVE: This study was undertaken to compare the rates of postoperative infectious complications of neurosurgery with prophylactic ceftriaxone and ampicillin/sulbactam, a less-expensive antibiotic . METHODS: Consecutive patients undergoing neurosurgery between January and December 1998 were recruited for the study . Those who had an infectious disease for which antibiotics were required, who received antibiotics within 48 hours before surgery, were aged <12 or >85 years, had an indwelling catheter for the monitoring of intracranial pressure, or had a history of allergy to the study drugs were excluded . Before the operation, eligible patients were randomized to either ampicillin/sulbactam 3 g or ceftriaxone 2 g . Surgeons and patients were blinded to treatment assignment . The study drugs were administered by the anesthesiologist as an IV bolus after induction of general anesthesia . All patients were followed for 6 weeks postoperatively . If reoperation was required within 6 weeks of the original operation, the patient received the same antibiotic as during the first surgery, without further randomization . RESULTS: Over the 1-year study period, 180 consecutive patients undergoing neurosurgical operations were recruited . Surgical-site infection occurred in 2 (2.3%) patients in the ampicillin/sulbactam group and 3 (3.3%) in the ceftriaxone group; nonsurgical-site infection occurred in 25 (28.4%) patients in the ampicillin/sulbactam group and 15 (16.3%) in the ceftriaxone group . The between-group differences were not statistically significant, with the exception of surgical implantation of foreign material, which was performed sig- nificantly more frequently in the ceftriaxone group (P = 0.045) . In addition, 2 of 3 surgical-site infections in the ceftriaxone group involved foreign-material implantation; however, if these operations are omitted from the analysis, the difference between treatments remains nonsignificant . CONCLUSIONS: The results suggest that ampicillin/sulbactam and ceftriaxone are of similar prophylactic efficacy in clean neurosurgical operations . Because the acquisition cost of 2 g ceftriaxone is approximately 3 times greater than that of 3 g ampicillin/sulbactam, the latter may be more cost-effective than the former for neurosurgical prophylaxis; however, other relevant hospital-related costs were not assessed in this study.

Endoscopy, 2001 Sep, 33(9), 805 - 7
Regression of high-grade gastric B-cell lymphoma after eradication of Helicobacter pylori; Gretschel S et al.; Regression of high-grade gastric B-cell lymphoma after eradication of Helicobacter pylori with antibiotic therapy has recently been shown in a very small number of patients . We describe here a patient with a 5-cm polypoid gastric lymphoma, who received a 7-day course of triple therapy when the histopathology was unknown . A second endoscopic examination 4 weeks later showed partial tumor regression without biopsy evidence of malignancy . Endoscopic mucosectomy was performed 8 weeks after the initial diagnosis . Again, in the histological analysis of the specimen, no evidence of B-cell lymphoma could be found . To confirm that the original biopsies were from the same patient, DNA analyses were carried out which gave identical results . This case suggests that a subgroup of primary gastric B-cell lymphomas responds to eradication of H . pylori with antibiotic therapy.

Antimicrob Agents Chemother, 2001 Oct, 45(10), 2813 - 9
A ribosomal ATPase is a target for hygromycin B inhibition on Escherichia coli ribosomes; Ganoza MC et al.; We demonstrate that the transfer of fully charged aminoacyl-tRNAs into peptides directed by the MS2 RNA template requires both ATP and GTP, initiation factors (IF1, IF2, and IF3), elongation factors (EF-Tu, EF-Ts, and EF-G), and the ribosomal ATPase (RbbA) . The nonhydrolyzable analogue AMPPCP inhibits the reactions, suggesting that hydrolysis of ATP is required for synthesis . The RbbA protein occurs bound to ribosomes and stimulates the ATPase activity of Escherichia coli 70S and 30S particles . The gene encoding RbbA harbors four ATP binding domains; the C-terminal half of the protein bears extensive sequence similarity to EF-3, a ribosome-dependent ATPase . Here, we show that the antibiotic hygromycin B selectively inhibits the ATPase activity of RbbA . Other antibiotics with similar effects on miscoding, streptomycin and neomycin, as well as antibiotics that impair peptide bond synthesis and translocation, had little effect on the ATPase activity of RbbA on 70S ribosomes . Immunoblot analysis indicates that at physiological concentrations, hygromycin B selectively releases RbbA from 70S ribosomes . Hygromycin B protects G1494 and A1408 in the decoding region, and RbbA enhances the reactivity of A889 and G890 of the 16S rRNA switch helix region . Cross-linking and X-ray diffraction data have revealed that this helix switch and the decoding region are in close proximity . Mutations in the switch helix (889-890) region affect translational fidelity and translocation . The binding site of hygromycin B and its known dual effect on the fidelity of decoding and translocation suggest a model for the action of this drug on ribosomes.

Bioorg Med Chem, 2001 Oct, 9(10), 2549 - 56
A tetracycline-binding RNA aptamer; Berens C et al.; Aptamers are perfect tools to study the interaction of small ligands with RNA . To study the mode of interaction of tetracycline with RNA, we isolated aptamers with high affinity to this antibiotic via in vitro selection . One of the selected aptamers, cb28, which has a comparable affinity to tetracycline as the small ribosomal subunit, was characterised in more detail . Cb28 binds only to typical tetracyclines, while atypical tetracyclines are not recognised . The hydroxyl group at position 6 is an essential determinant for recognition, while modifications at positions 4, 5 and 7 do not interfere with RNA binding . Binding of tetracycline to cb28 is magnesium dependent . The secondary structure of cb28 was determined by lead cleavage and DMS modification . Upon tetracycline binding, nucleotides in J2/3 and the P5 stem-loop are protected from cleavage by lead, indicating a conformational change in the RNA . This conformational change was confirmed by tetracycline dependent changes in the DMS modification pattern . Photo-induced affinity incorporation of tetracycline into cb28 resulted in a crosslink to position G76, a residue in L5 . The mode of binding of tetracycline to the cb28 aptamer resembles its interaction with the primary binding site on the small ribosomal subunit.

Diabet Med, 2001 Jul, 18(7), 567 - 72
Fungal infection of the diabetic foot: two distinct syndromes; Heald AH et al.; AIMS: Fungal infection of diabetic foot ulcers has not been described . We analysed the features of 17 patients with diabetic foot ulcers probably infected with fungi . METHODS: Seventeen patients were identified with clinically infected foot ulcers, (i) which had failed to heal despite prolonged antibiotic therapy and intensive podiatric care, (ii) from which Candida spp . was isolated or hyphae +/- yeasts were visualized in material from ulcers or surrounding skin . RESULTS: Multiple ulcers arising simultaneously were present in 10 patients (59%), preceded by blistering in seven cases . Single ulcers with markedly ulcerated margins were present in seven (41%) patients and were preceded by blisters in two . All 17 cases had neuropathy and 15 (88%) had severe peripheral vascular disease . All ulcers responded to antifungal therapy . CONCLUSIONS: Candida spp . is associated with two distinctive patterns of protracted ulceration in diabetic feet which improve following systemic antifungal therapy . Diabet . Med . 18, 567-572 (2001)

World J Urol, 2001 Aug, 19(4), 234 - 9
Role of cathepsin D in prostatic cancer cell growth and its regulation by brefeldin A; Konno S et al.; We investigated a possible relationship between brefeldin A (BFA), an antibiotic, and cathepsin D (Cat.D), a lysosomal protease, in prostate cancer proliferation . Effects of BFA (30 ng/ml) were examined on the growth of three human prostatic cancer cell lines, PC-3, DU-145, and LNCaP cells . Its effect on Cat.D in these cancer cells was assessed by Western blots and compared with Cat.D expressed in clinical prostate specimens (n = 55) . BFA profoundly (> 70%) inhibited the growth of all three cancer cell lines . Western blots revealed that expression of procathepsin D (Pro.Cat.D) was markedly increased with BFA, whereas actively proliferating (control) cells greatly exhibited mature Cat.D . Analysis of prostate specimens then showed predominant Pro.Cat.D expression in non-cancerous tissues while also showing enhanced expression of mature Cat.D in all cancer specimens . Therefore, BFA-induced growth inhibition in prostatic cancer cells is associated with a blocking of Cat.D maturation (activation), suggesting a possible role of Cat.D in prostate cancer proliferation/development.

Bull Exp Biol Med, 2001 May, 131(5), 505 - 10
Anthracycline-induced cardiomyopathy is manifested in decreased protein synthesis, impaired intracellular regeneration, and non-necrotic death of cardiomyocytes; Semenov DE et al.; The cytostatic anthracycline antibiotic daunomycin hydrochloride led to the development of plastic myocardial insufficiency characterized by impaired intracellular regeneration of cardiomyocytes and progressive involution of cytoplasmic structures . Morphological signs of plastic myocardial insufficiency included fragmentation, annulation, or collapse of nucleoli in cardiomyocyte nuclei, lysis of myofilaments, sarcomeres, or myofibrils, focal degradation of the cytoplasm, and intensive autophagy . Fatal anthracycline-induced cardiac insufficiency was associated with massive cardiomyocyte loss due to their non-necrotic death and elimination . Our findings indicate that anthracycline-induced cardiomyopathy in laboratory animals is a convenient model for studying general mechanisms underlying the pathogenesis of regenerative and plastic cardiac insufficiency in humans.

Minerva Ginecol, 2001 Oct, 53(5), 351 - 6
{Current clinical features of septic abortion in Western countries . A series of cases observed during 1998 at the 1st and 2nd department of obstetrics and gynecology of the University of Rome La Sapienza}; Spina V et al.; BACKGROUND: Advances in diagnostic techniques and therapy and the institution of both legislative measures and Centres for the protection of mother-infant health are major factors to which the reduced incidence of septic abortion in should probably be ascribed in Western Countries, where it reaches approximately 10% . The aim of this study was to analyse the current problems related to this pathology in a Western Country, such as Italy . METHODS: Cases of septic abortion observed at the I and II Department of Obstetrics and Gynaecology of University of Rome La Sapienza during 1998 were retrospectively analysed . RESULTS: 42 cases of septic abortion were observed . Fever was present in 100 % of cases, genital bleeding in 57 %, abdominal-pelvic pain in 16.7%, genital purulent discharge in one case (2.4%), pain of the fornices at vaginal examination in another (2.4%) . Leucocytosis was detected in 21.5% of patients . Disseminated intravascular coagulation (DIC) occurred in one patient (2.4%) . No maternal deaths were observed . Antibiotic therapy was carried out in 81% of cases, a uterine curettage in 95.2% . CONCLUSIONS: Currently, the possibility of early diagnosis of abortion due to the routine use of ultrasonography and, as a consequence, of early antibiotic therapy, whenever a sepsis is suspected, account for the predominance of mild or even doubtful clinical pictures of this pathology in Western Countries . Nevertheless, severe complications are possible in the case of septic abortion, including septicaemia, septic shock, DIC, renal insufficiency . Thus, a correct and careful attitude of prophylaxis and therapy is required.

J Neurosci, 2001 Sep 15, 21(18), 7013 - 25
FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel; Gale JE et al.; Hair cells in mouse cochlear cultures are selectively labeled by brief exposure to FM1-43, a styryl dye used to study endocytosis and exocytosis . Real-time confocal microscopy indicates that dye entry is rapid and via the apical surface . Cooling to 4 degrees C and high extracellular calcium both reduce dye loading . Pretreatment with EGTA, a condition that breaks tip links and prevents mechanotransducer channel gating, abolishes subsequent dye loading in the presence of calcium . Dye loading recovers after calcium chelation with a time course similar to that described for tip-link regeneration . Myo7a mutant hair cells, which can transduce but have all mechanotransducer channels normally closed at rest, do not label with FM1-43 unless the bundles are stimulated by large excitatory stimuli . Extracellular perfusion of FM1-43 reversibly blocks mechanotransduction with half-blocking concentrations in the low micromolar range . The block is reduced by high extracellular calcium and is voltage dependent, decreasing at extreme positive and negative potentials, indicating that FM1-43 behaves as a permeant blocker of the mechanotransducer channel . The time course for the relief of block after voltage steps to extreme potentials further suggests that FM1-43 competes with other cations for binding sites within the pore of the channel . FM1-43 does not block the transducer channel from the intracellular side at concentrations that would cause complete block when applied extracellularly . Calcium chelation and FM1-43 both reduce the ototoxic effects of the aminoglycoside antibiotic neomycin sulfate, suggesting that FM1-43 and aminoglycosides enter hair cells via the same pathway.

Pigment Cell Res, 2001 Aug, 14(4), 275 - 82
Efficient, long-term transgene expression in Xenopus laevis dermal melanophores; Gatlin J et al.; Xenopus laevis dermal melanophores provide an excellent model system for the investigation of complex cellular processes . Specifically, the expression of exogenous genes in Xenopus melanophores is the basis of recombinant bioassays for the study of receptor-ligand interactions . However, due to their slow rate of cell division and to the relatively low efficiency of current transfection protocols, long-term expression of exogenous genes and the generation of stable melanophore cell lines remains problematic . In this report we demonstrate the efficient, long-term expression of two exogenous proteins, the enhanced green fluorescent protein (EGFP) and the human CD4 (hCD4) cell surface receptor, following stable introduction into Xenopus melanophores via an HIV-1 based vector . Transduction of melanophores with the EGFP expression vector resulted in up to 80% EGFP+ cells . After 1 year in continuous culture in the absence of antibiotic selection, more than 60% of the cells remained EGFP+ . Furthermore, we demonstrate the expression of hCD4 melanophores for over 9 months in continuous culture in the absence of antibiotic selection . Our results indicate that lentivirus vectors provide an efficient means of introducing genetic information into Xenopus melanophores, resulting in sustained levels of gene expression . The significance of this gene transfer system for the study of cellular signal transduction pathways is discussed.

Cell Transplant, 2001, 10(4-5), 499 - 502
Tissue-engineered pancreatic islets: culturing rat islets in the chitosan sponge; Cui W et al.; Subcutaneous islet transplantation has become an attractive modality . With development of tissue-engineering techniques, it is possible to rectify the disadvantage of poor blood supply in the subcutaneous site by reconstruction of the capillary network . According to reports, the Chitosan sponge (CS) could be used for reconstruction of in vitro capillary-like network and could be used in artificial skin equivalent . In this study, we cultured the islets in CS for future application . CSs, having 200-500 microm pore size, were prepared by freeze-drying method . Rat islets were isolated from the pancreas of Lewis rats (10 weeks old, 280-300 g, male) by collagenase digestion followed by discontinuous dextran gradient centrifugation method . Each 20 islets were seeded equally into the CSs and were cultured for 62 days with various culture media such as RPMI-1640, Dulbecco's modified Eagle's medium (DMEM), and Eagle's MEM . They contained 10% fetal bovine serum (FBS) and 5 ml/L antibiotic-antimycotic mixed stock solution in the culture dishes . Insulin concentration both inside and outside of the islet-seeded CS was measured during culture . Changes in the morphology of islets were also observed in this study . Freshly isolated islets had a loose appearance with an irregular border, and most were seen as a single islet . Occasionally a cluster, consisting of 2-4 islets ranging mainly from 150 to 250 microm in diameter, was observed . Islets cultured in the CSs in different culture media retained initial morphology, which had well-delineated smooth borders for at least 53 days . The insulin release behavior of islets cultured in the CS showed constant secretory capacities for 49 days . After that they exhibited a rapid and definitive decline from the initial insulin release . Until this stage, insulin concentration in the CS was well maintained . The properties were dependent on culture medium used and insulin diffusion released from islets . This experiment is a new study model for establishment of islet culture in a three-dimensional matrix . Also extension of this observation will provide new insights for islet transplantation at the subcutaneous site by a tissue-engineering approach.

Aust Vet J, 2001 Jul, 79(7), 492 - 6
Pharmacokinetics and residues in milk of oxytetracyclines administered parenterally to dairy goats; Rule R et al.; OBJECTIVE: To determine for two commercial preparations of oxytetracycline (OTC) the pharmacokinetic behaviour, the presence of detectable milk residues and the penetration in milk of OTC administered by intravenous (IV) (conventional formulation {CF}) and intramuscular (IM) routes (CF and long-acting {LA} formulations) in goats producing milk . The effects of these formulations on plasma activity values of creatine kinase (CK) and lactate dehydrogenase (LDH) were also determined as indicators of tissue damage . PROCEDURE: Five healthy lactating goats producing 1.5+/-0.5 L/d milk and weighing 56.0+/-4.8 kg were used . Single doses of OTC chlorhydrate (CF) were administered (20 mg OTC/kg) by IV (Trial 1 IV) and IM (Trial 1 IM) routes and OTC dehydrate (LA) by the IM route . The same goats were first given IV CF, then IM CF followed by IM LA with 3 weeks between each treatment . Blood and milk samples were taken . The quantification of OTC was performed by HPLC and the plasma activities of CK and LDH enzymes were determined by spectrophotometry . The presence of OTC residues in milk was determined by a commercial reagent . The plasma pharmacokinetic parameters were calculated using a two-compartment model . RESULTS: Estimates of kinetic variables following IV administration were: Vss= 400.0+/-120.0 mL/kg and CL= 110.0+/-14.0 (mL/h)/kg . The t(fi) for IV= 3.0+/-0.3 h; IM, CF = 10.5+/-2.1 h and IM, LA = 15.1+/-3.1 h . The concentration of OTC in milk at 48 h was: IV= 0.6+/-0.4; IM CF= 1.1+/-0.2 and at 72 h (IM LA)= 0.6+/-0.1 microg/mL and the penetration in milk of OTC was: IV= 70.0+/-18.0; IM CF= 79.0+/-14.0 and IM LA= 66.0+/-6.0% . The areas under the curve of CK and LDH activities in plasma were calculated by the trapezoidal method . Values of CK and LDH IM, LA were greater (P < 0.05) than those observed for IM, CF at 2 and 3 days after administration of the antibiotic . Finally, the bioavailability of OTC CF = 92.0+/-22.0 and LA= 78.0+/-23.0% was suitable for its usage by the IM route in lactating goats . CONCLUSION: Plasma concentration-time values of OTC administered parenterally in production dairy goats showed similar bioavailability for the two pharmaceutical preaprations . The presence of detectable residues in milk indicates that milk should not be used for human consumption for 2 and 3 days after administration of conventional and long-acting formulations, respectively . The increments in CK and LDH activities after the IM administration of LA are consistent with the presence of tissue damage provoked by the pharmaceutical preparations at the injection site.

Bone Marrow Transplant, 2001 Jun, 27(12), 1287 - 92
Administration of post-autologous PBSCT rhG-CSF is associated with long-term low concentrations of bone marrow hematopoietic progenitor cells; Osma MM et al.; Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been widely used after autologous peripheral blood stem cell transplant (APBSCT) in an attempt to reduce the duration of neutropenia, but whether this treatment has any influence on long-term engraftment remains unknown . We have retrospectively analyzed data from breast cancer patients to compare post-APBSCT rhG-CSF administration in terms of the short-term benefit and myeloid marrow regeneration after 1 year . Group A included 10 patients not treated with post-APBSCT rhG-CSF, while groups B and C comprised 15 and 13 patients treated with this drug from days +1 and +6, respectively . No differences among the three groups were found in age, diagnosis, previous chemo-radiotherapy, CD34+/CD71- cell concentration in pre-transplant bone marrow (BM), mobilization schedule, CD34+ cell yield, conditioning regimen and post-transplant radiotherapy . Post-APBSCT rhG-CSF was shown to accelerate neutrophil recovery, but there were no significant differences in platelet recovery, transfusion requirements, days of fever, antibiotic administration or inhospital stay . With regard to BM hematopoietic precursors 1 year after APBSCT, significantly lower concentrations of total CD34+ cells, committed CD34+/CD33+ subsets, and more immature CD34+/CD71- cells were found in both groups B and C compared with patients not having received the cytokine (group A) . Thus, post-APBSCT rhG-CSF administration does not appear to beneficially affect procedure outcome, and might even impair long-term marrow hematopoiesis.

Antibiot Khimioter, 2001, 46(3), 6 - 11
{Increase in eremomycin production by regeneration and UV-irradiation of Amycolatopsis orientalis subsp . eremomycini protoplasts}; Trenin AS et al.; Protoplast regeneration of Amycolatopsis orientalis subsp . eremomycini producing eremomycin leads to the change of cultural and morphological properties as well as synthesis of secondary metabolites . Formation of plus-variants with enchanced antibiotic production was promoted by UV-irradiation of protoplasts . These plus-variants can be successfully used for repeating protoplasting--UV-irradiation of protoplasts with further increasing of the strain productivity . Finally activity of the initial A . orientalis culture was increased 7-8 times . Proposed method is recommended for the improvement of actinomycetes strains producing antibiotics especially in the case of cultures with poor sporulation.

Eur Biophys J, 2001 Aug, 30(4), 233 - 41
Alamethicin channel conductance modified by lipid charge; Aguilella VM et al.; The membrane surface charge modifies the conductance of ion channels by changing the electric potential and redistributing the ionic composition in their vicinity . We have studied the effects of lipid charge on the conductance of a multi-state channel formed in planar lipid bilayers by the peptide antibiotic alamethicin . The channel conductance was measured in two lipids: in a neutral dioleoylphosphatidylethanolamine (DOPE) and a negatively charged dioleoylphosphatidylserine (DOPS) . The charge state of DOPS was manipulated by the pH of the membrane-bathing solution . We find that at high salt concentrations (e.g., 2 M NaCl) the effect of the lipid charge is below the accuracy of our measurements . However, when the salt concentration in the membrane-bathing solution is decreased, the surface charge manifests itself as an increase in the conductance of the first two channel levels that correspond to the smallest conductive alamethicin aggregates . Our analysis shows that both the salt and pH dependence of the surface charge effect can be rationalized within the nonlinear Poisson-Boltzmann approach . Given channel conductance in neutral lipids, we use different procedures to account for the surface charge (e.g., introduce averaging over the channel aperture and take into account Na+ adsorption to DOPS heads), but only one adjustable parameter: an effective distance from the nearest lipid charge to the channel mouth center . We show that this distance varies by 0.3-0.4 nm upon channel transition from the minimal conducting aggregate (level L0) to the next larger one (level L1) . This conclusion is in accord with a simple geometrical model of alamethicin aggregation.

Science, 2001 Sep 7, 293(5536), 1786 - 90
Humans as the world's greatest evolutionary force; Palumbi SR; In addition to altering global ecology, technology and human population growth also affect evolutionary trajectories, dramatically accelerating evolutionary change in other species, especially in commercially important, pest, and disease organisms . Such changes are apparent in antibiotic and human immunodeficiency virus (HIV) resistance to drugs, plant and insect resistance to pesticides, rapid changes in invasive species, life-history change in commercial fisheries, and pest adaptation to biological engineering products . This accelerated evolution costs at least $33 billion to $50 billion a year in the United States . Slowing and controlling arms races in disease and pest management have been successful in diverse ecological and economic systems, illustrating how applied evolutionary principles can help reduce the impact of humankind on evolution.

Electrophoresis, 2001 Aug, 22(13), 2755 - 7
Reversed-polarity capillary zone electrophoretic analysis of usnic acid; Kreft S et al.; A capillary zone electrophoretic (CZE) method for the determination of usnic acid is described for the first time . Usnic acid is an antibiotic substance from lichens . Due to its low solubility in water, a high content of methanol in CZE buffer is required . Because of the methanol in the buffer, the electroosmotic flow velocity was lower than the electrophoretic mobility of usnic acid . Accordingly, the use of reversed-polarity (with the anode on the detector side of the capillary) was necessary . The optimal buffer composition was 50 mM NaOH, 20 mM acetic acid and 5% water in methanol . The detection limit of UV detector at 290 nm for usnic acid in the injected extract was 3.5 mg/L and the relative standard deviation of the normalized peak area was 3.3% at 250 mg/L.

Electrophoresis, 2001 Aug, 22(13), 2746 - 54
Electrophoretically mediated microanalysis of gentamicin with in-capillary derivatization and UV detection; Kaale E et al.; This paper describes a system for integration of a one-step-microscale chemical derivatization and analysis by a methodology known as electrophoretically mediated microanalysis (EMMA) . Differential electrophoretic mobility between an analyte, reagent, and their product offers EMMA a unique capability to selectively carry out electrophoretic mixing, control product formation, and separation . This system was successfully applied to perform derivatization and separation of the multicomponent aminoglycoside antibiotic gentamicin using 1,2-phthalic dicarboxaldehyde and mercaptoacetic acid as labeling reagents . A multivariate approach based on central composite experimental design was used to optimize the derivative yield . Full automation of the derivatization and analytical procedure, high derivatization efficiency, high sample throughput, and precision are the excellent features of the present method . In addition, this methodology offers short analysis time, as well as selectivity and sensitivity suitable for impurities determination . Separation of gentamicin C1, C1a, C2, C2a, C2b, sisomicin, and several minor components was achieved . For the first time separation and identification of three impurities, namely garamine, 2-deoxystreptamine, and paromamine are described.

Mediators Inflamm, 2001 Jun, 10(3), 101 - 7
Competition of IL-1 and IL-1ra determines lymphocyte response to delayed stimulation with PHA; Dabrowski MP et al.; BACKGROUND: Human peripheral blood mononuclear cells (PBMC) left in microcultures for 24h without mitogen do not respond to subsequent stimulation with PHA . They regain reactivity if the native culture medium is absorbed with other party lymphocytes or partially replaced with the medium from a PHA-stimulated culture . The observations suggest that, during the incubation, some inhibitory agent had accumulated in the culture medium . AIM: The study was performed to determine the nature of the observed phenomenon in respect of the possible role of monocytes and their products IL-1 and IL-1 receptor antagonist (IL-1ra), and to test for immunodiagnostic purposes the significance of quantifying the lymphocyte response to delayed stimulation with PHA in patients suffering from inflammatory prosesses . METHODS: Lymphocyte response to delayed stimulation with PHA, calculated as the lymphocyte-monokine interaction (LM) index, was determined in the microcultures of PBMC isolated from the blood of healthy donors or of patients with acute tonsilitis . The values of LM indices were compared with the ratios of IL-1ra/IL-1beta concentration estimated by enzyme-linked immunosorbent assay method in the culture supernatants . The influences of exogenous IL-1beta, IL-1ra, anti-IL1ra antibodies and antibiotic cefaclor on the monokine concentrations and on the values of LM index were tested . RESULTS AND CONCLUSIONS: The results show that the level of lymphocyte response to delayed stimulation with PHA (LM index) is inversely proportional to the ratio of IL-1ra/IL-1beta concentration in the culture . The low LM values at high IL-1ra/IL-1beta ratios in PBMC cultures from healthy donors, reversed proportions found in patients' PBMC (acute tonsilitis), and the cefaclor-induced reduction of LM value with correlated increase of the IL-1ra/IL-1beta ratio suggest that the LM assay may prove to be useful for immunodiagnostic purposes.

HNO, 2001 Aug, 49(8), 654 - 7
{Ocular myositis . A rare differential diagnosis of sinus-induced orbital complications}; Neumann A et al.; Orbital myositis is an uncommon subgroup of the nonspecific orbital inflammatory syndromes (previously termed orbital pseudotumor) and presents with eyelid swelling and redness, conjunctival chemosis, pain, proptosis, and diplopia . The disease is to date of unknown origin; autoimmune processes are suspected for the etiology . In the case of an otherwise healthy young male patient (age 28 years), the coexistence of chronic sinusitis primarily led to the diagnosis of sinugen orbital cellulitis . Despite antibiotic drug administration and surgical drainage of the paranasal sinuses the symptoms persisted . A second computed tomography revealed fusiform, inflammatory enlargement of the m . rectus lateralis . This muscle showed a restrictive paresis so that initially the m . rectus medialis was suspected to be paretic . The patient responded dramatically to administration of prednisolone within 2 days . The differential diagnosis between a sinugen orbital complication and orbital myositis is significant because corticosteroids are contraindicated for orbital cellulitis whereas they remain the therapy of choice for orbital myositis.

Eur J Orthod, 2001 Aug, 23(4), 363 - 72
Orthodontic treatment of patients with medical disorders; Burden D et al.; This article will highlight some of the problems encountered when orthodontic treatment is provided for patients who have serious medical conditions . The way in which various disease processes might influence treatment decisions will be described, as well as recommended methods of avoiding potential problems.

J Pharm Sci, 2001 Aug, 90(8), 1066 - 75
The kinetics of the alkaline degradation of daptomycin; Muangsiri W et al.; The aqueous degradation of daptomycin, a lipopeptide antibiotic, was investigated as a function of substrate concentration (0.5-10.0 mM), pH (9.0-10.5), buffer concentration (0.06-0.20 M borate, glycinate, or carbonate buffers), temperature (20-50 degrees C), and ionic strength (0.1-0.8) . The primary degradation pathway was determined by electrospray-mass spectroscopy (ES-MS), Fourier transform infrared (FTIR), and fluorescence spectroscopy to be hydrolysis of the ester linkage between the C-terminus (kynurenine) and the side chain of the fourth residue (threonine) . The reaction was first order with respect to time; however, the reaction order with respect to substrate concentration was <1 at substrate concentrations >1 mM . Insignificant buffer effect was observed . The reaction was subject to specific base catalysis . Activation parameters were E(a) = 13.6 kcal/K.mol, DeltaH++ = 13.0 kcal/K.mol, and DeltaS++ = -19.2 eu . The positive primary salt effect was observed with negative deviation at high concentration of salt . The magnitude of the salt effect depended on salt identities in the order sodium < potassium < calcium chloride .

Dis Colon Rectum, 2001 Aug, 44(8), 1100 - 5
Impact of a surgeon-trained observer on accuracy of colorectal surgical site infection rates; Miransky J et al.; PURPOSE: The aims of this study were 1) to establish accurate and reproducible baseline surgical site infection rates for our department and 2) to identify risk factors associated with surgical site infection in patients undergoing surgery on a colorectal service . METHODS: Phase I--Surgical site infection grading between the surgeon-trainer and the observer-trainee was validated using a four-point scale for wound evaluation previously used by our institution . Phase II--Patients undergoing colorectal surgery were prospectively monitored . The observed surgical site infection rate was compared with morbidity and mortality reports . Patient and perioperative variables were analyzed for their effect on surgical site infection using the chi-squared test . Risk factors approaching significance on univariate analysis (P < 0.2) were entered into a multivariate stepwise logistic regression model . RESULTS: Concordance on surgical site infection grading between the surgeon-trainer and the observer-trainee improved from an initial 79 percent to 96 percent during the validation period . The surgeon-trained observer reported a surgical site infection rate of 7.2 percent vs . a morbidity and mortality reported rate of 3.3 percent . Among the variables examined, obesity and surgical procedure category were significantly associated with surgical site infection rates . The effect of prophylactic antibiotics and prior chemotherapy, radiation, or steroid therapy on surgical site infection rates approached significance . A logistic regression analysis incorporating these risk factors for surgical site infection accurately predicted infection status 93 percent of the time . CONCLUSION: Use of a surgeon-trained observer doubles the detection rate of postoperative surgical site infection . Accurate, prospective assessment identifies risk factors significantly associated with increased surgical site infection rates in colorectal surgical patients.

Ophthalmology, 2001 Sep, 108(9), 1562 - 4
Pediatric dacryocystorhinostomy for nasolacrimal duct obstruction; Barnes EA et al.; OBJECTIVE: To determine the outcome of pediatric dacryocystorhinostomy (DCR) for large mucoceles or for primary nasolacrimal duct obstruction unresponsive to multiple probings . DESIGN: Retrospective noncomparative case series . PARTICIPANTS: One hundred thirty-four external dacryocystorhinostomies were performed in 121 children . METHODS: Clinical case notes were reviewed for a series of cases operated on at Moorfields Eye Hospital by specialist lacrimal surgeons between 1987 and 1999 . MAIN OUTCOME MEASURES: Postoperative relief of presenting symptoms and signs and complications . RESULTS: Fifty-nine percent of admissions (75 of 127) were day cases, and the other 52 admissions were inpatient . Simultaneous bilateral surgery was performed in 7 of 121 (6%) children, all but one having day case admission, and sequential bilateral surgery in 6 of 121 (5%) cases . Silicone intubation was performed in 20% of operations, these generally being early in the series . Three children had Down syndrome, five had craniofacial anomalies, and two had systemic disorders . Mild postoperative cellulitis occurred in three cases, all of which settled without complication after systemic antibiotic therapy, and there was one case of suture granuloma . There were no cases of immediate postoperative complication in either the day case or the inpatient groups . Complete cure of symptoms was achieved in 96% and an improvement of symptoms (with mild persistence of epiphora under challenge) in five cases (4%) . CONCLUSION: For surgeons experienced in pediatric lacrimal surgery, external DCR with sutured mucosal flaps can be accomplished through an 8-mm incision with no surface sutures and minimal scarring . Symptoms are improved in all cases and complete cure achieved in 96%, with no immediate postoperative complications and only few (3%) short-term complications . The surgery is amenable to day case management, without significant morbidity, and may be performed as a simultaneous bilateral procedure.

Pediatrics . 2001 Sep;108(3):E57.
Technical report: evidence for the diagnosis and treatment of acute uncomplicated sinusitis in children: a systematic overview; Ioannidis JP et al.; OBJECTIVE: To evaluate and analyze the existing evidence for the diagnosis and treatment of acute uncomplicated sinusitis in children . DESIGN: A systematic overview and meta-analysis considered all pertinent studies with at least 10 children younger than 18 years with acute symptoms of <30 days and without serious complications . OUTCOMES: Clinical improvement rates for intervention studies of antibiotics or ancillary measures; concordance of diagnostic tests (expressed as likelihood ratios) . RESULTS: Of 1857 citations originally reviewed, we identified 21 qualifying studies, compared with 450 reports on complications of acute sinusitis and 233 nonsystematic reviews of the subject . The qualifying studies included 5 randomized, controlled trials and 8 case series on antibiotic therapy, 3 randomized, controlled trials on ancillary treatments, and 8 studies with information on diagnostic tests (including 3 therapeutic trials) . Definitions and inclusion criteria were heterogeneous across studies . The pooled clinical improvement rate with antibiotics was 88% (177/202) in randomized, controlled trials and 92% (318/345) in nonrandomized studies; the improvement rates on no antibiotics were 60% and 80%, respectively . Improvement rates were significantly higher in nonrandomized studies (Mantel-Haenszel odds ratio: 1.79; 95% CI: 1.05-3.04, stratified for use of antibiotics) . Data on ancillary measures were sparse and heterogeneous . In studies comparing clinical findings with plain film radiography, the pooled rate of abnormal radiographic findings against a clinical diagnosis of sinusitis was 73% (596/814; range: 55% to 96% between studies) . There was poor concordance between clinical criteria, plain radiographs, ultrasonography, computed tomography, and fluid on aspiration in all available paired assessments (all positive likelihood ratios were </=4 and all negative likelihood ratios were >/=0.2) . CONCLUSIONS: Good, high-quality evidence for acute uncomplicated sinusitis in children is limited . Diagnostic modalities show poor concordance, and treatment options are based on inadequate data . More evidence is needed for defining the optimal treatment and diagnostic methods for this common condition.

Pediatrics, 2001 Sep, 108(3), 741 - 8
Early postnatal dexamethasone therapy for the prevention of chronic lung disease; Vermont Oxford Network Steroid Study Group; OBJECTIVE: To test the hypothesis that early postnatal dexamethasone will reduce the incidence of death or chronic lung disease (CLD) in ventilated extremely low birth weight premature infants . DESIGN: Multicenter randomized double-blinded controlled clinical trial . SETTING: A total of 42 neonatal intensive care units in the Vermont Oxford Network . PARTICIPANTS: Infants weighing 501 to 1000 g were eligible for enrollment at 12 hours of age if they needed assisted ventilation, had received surfactant replacement therapy, were physiologically stable, had no obvious life-threatening congenital anomaly, and had blood cultures obtained and antibiotic therapy initiated . INTERVENTION: Infants were randomly assigned to dexamethasone or saline placebo . Intravenous dexamethasone was administered for 12 days according to the following dosing schedule: 0.5 mg/kg/d for 3 days, 0.25 mg/kg/d for 3 days, 0.10 mg/kg/d for 3 days, 0.05 mg/kg/d for 3 days . Infants in either group could receive treatment with selective late postnatal steroids beginning on day 14 of life if they were on assisted ventilation with supplemental oxygen greater than 30% . OUTCOME MEASUREMENTS: The primary outcome measure was CLD or death at 36 weeks postmenstrual age . RESULTS: The study was stopped before completion of sample size goals because of concern about serious side effects in the early steroid treatment group . A total of 542 infants were enrolled (early treatment N = 273, control N = 269) . The 2 groups had similar demographic characteristics . No differences were noted in the primary outcome of CLD or death at 36 weeks postmenstrual age (early treatment 50% vs control: 53%, relative risk: 0.93; 95% confidence interval {CI}: 0.79-1.09) . Fewer infants who received early steroid treatment had a patent ductus arteriosus (relative risk: 0.78; 95% CI: 0.63-0.96), and fewer infants in the early steroid group received indomethacin therapy (relative risk: 0.74; 95% CI: 0.64-0.86) or late steroid treatment (relative risk: 0.69; 95% CI: 0.58-0.81) . However, more infants who received early steroid treatment had complications associated with therapy including an increase in hyperglycemia (relative risk: 1.29; 95% CI: 1.13-1.46) and an increase in the use of insulin therapy (relative risk: 1.62; 95% CI: 1.36-1.94) . A trend toward increased gastrointestinal hemorrhage (relative risk: 1.55; 95% CI: 0.92-2.61), gastrointestinal perforation (relative risk: 1.53; 95% CI: 0.89-2.61), and an increased systolic blood pressure (relative risk: 1.34; 95% CI: 0.97-1.85) was noted . In infants receiving cranial ultrasound examinations, a marginal increase in periventricular leukomalacia was noted in the early steroid treatment group (relative risk: 2.23; 95% CI: 0.99-5.04) . Infants who received early steroid therapy had fewer days in supplemental oxygen but experienced poor weight gain . CONCLUSIONS: A 12-day course of early postnatal steroid therapy given to extremely low birth weight infants did not decrease the risk of CLD or death at 36 weeks postmenstrual age and was associated with an increased risk of complications and poor weight gain.

J Dermatol Sci, 2001 Oct, 27(2), 147 - 51
Potential anti-androgenic activity of roxithromycin in skin; Inui S et al.; Since acne formation is a multistep process accelerated by androgens, we examined whether a new anti-acne antibiotic roxithromycin (RXM) may act as anti-androgen using transient transfection assays in human skin fibroblasts . The result showed no significant effect of 0.5, 1 and 5 microg/ml RXM on 10(-9) M R1881-induced androgen receptor (AR) transcriptional activity . While the cotransfection of exogenous ARA55, a novel AR coactivator, increased AR transactivation up to 2.59-fold, this increase was attenuated by 5 microg/ml RXM to 64.7% . Semiquantitative RT-PCR results showed that 0.1 mM H(2)O(2) treatment increased ARA55 mRNA expression level, indicating that reactive oxygen species increase the expression of ARA55 in skin . These results suggest that RXM may serve as anti-androgen only in the hypersensitive state to androgen, but not in the physiological state, through modulating end-organ hypersensitive condition to androgen possibly involving the pathway from reactive oxygen species to ARA55.

Gynecol Oncol, 2001 Aug, 82(2), 329 - 32
Predictors of complications after inguinal lymphadenectomy; Gould N et al.; OBJECTIVE: The aim of this study was to identify predictors of complications in patients undergoing inguinal lymphadenectomy (LND) in the treatment of vulvar carcinoma . METHODS: Clinical information was abstracted from records of patients with invasive vulvar cancer . All patients underwent LND . Closed suction drains were placed in groin incisions and removed when output was less than 30 ml/24 h . Associations between variables were studied by chi(2) and t tests . RESULTS: Sixty-seven patients undergoing 112 LND were evaluated . Eighty-eight percent of patients underwent radical vulvar surgery and LND while 12% underwent LND alone . Patients were treated with either unilateral (22) or bilateral (45) LND . Seventy-three percent received extended postoperative prophylactic antibiotics . The median duration of suction drainage was 15 days for one drain and 14 days for two drains . Early postoperative cellulitis (<30 days after surgery) developed in 35.4%, early wound breakdown in 19.4%, early lymphedema in 4.8%, and early lymphocyst formation in 13.1% . Late cellulitis (>30 days after surgery) developed in 22.2%, late wound breakdown in 3.2%, late lymphedema in 29.5%, and late lymphocysts in 5% . Patients developing early cellulitis were more likely to have early wound breakdown (P = <0.001, RR 14.2) or early lymphocyst formation (P = 0.016, RR 7.6) . Type of procedure, antibiotic use, need for adjuvant therapy, and duration of suction drainage did not influence early complications . Early complications and management strategies did not predict late complications . CONCLUSIONS: Chronic lymphedema occurs in nearly 30% of patients after LND . Late complications after LND were not predicted by early complications . New strategies for prevention of chronic lymphedema are needed .

Prikl Biokhim Mikrobiol, 2001 Jul-Aug, 37(4), 444 - 52
{Effect of cloned DNA fragment from Streptomyces chrysomallus No.2 on metabolism in Streptomyces strains}; Novozhilova TIu et al.; The effects on cloned DNA fragment carrying an actinomycin resistance determinant on physiological processes in streptomyces strains with various potencies in producing this antibiotic, their inactive mutants, and model strain of Streptomyces lividans 66 were studied . This fragment was shown to modulate bacterial resistance to actinomycin and biosynthesis of antibiotics.

Am J Med, 2001 Aug 15, 111(3), 203 - 10
A statewide initiative to improve the care of hospitalized pneumonia patients: The Connecticut Pneumonia Pathway Project; Meehan TP et al.; PURPOSE: A statewide quality improvement initiative was conducted in Connecticut to improve process-of-care performance and to decrease length of stay for patients hospitalized with community-acquired pneumonia . SETTING AND METHODS: Data were collected on 1,242 elderly (> or =65 years) pneumonia patients hospitalized at 31 of 32 acute care hospitals between January 16, 1995, and March 15, 1996, and on 1,146 patients hospitalized between January 1, 1997, and June 30, 1997 . Interventions included feedback of performance data (Qualidigm, the Connecticut Peer Review Organization), dissemination of an evidence-based pneumonia critical pathway (Connecticut Thoracic Society), and sharing of pathway implementation experiences (hospitals) . Process and outcome measures included early antibiotic administration, blood culture collection, oxygenation assessment, length of stay, 30-day mortality, and 30-day readmission rates . Analyses were adjusted for severity of illness and hospital-specific practice patterns . RESULTS: After the statewide initiative, improvements were noted in antibiotic administration within 8 hours of hospital arrival (improvement from 83.4% to 88.8%, relative risk {RR} = 1.21; 95% confidence interval {CI}: 1.10 to 1.32), oxygenation assessment within 24 hours of hospital arrival (93.6% to 95.4%; RR = 1.23, 95% CI: 1.11 to 1.38), and length of stay (7 days to 5 days, P <0.001) . There were no significant changes in blood culture collection within 24 hours of hospital arrival, blood culture collection before antibiotic administration, 30-day mortality, or 30-day readmission rates . CONCLUSIONS: Statewide improvements were demonstrated in the care of hospitalized pneumonia patients concurrent with a multifaceted quality improvement intervention . Further research is needed to separate the effects of the quality improvement interventions from secular trends.

Br J Haematol, 2001 Aug, 114(2), 319 - 26
Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study; Vellenga E et al.; The present study analysed whether autologous peripheral blood stem cell transplantation (PSCT) improves engraftment, quality of life and cost-effectiveness when compared with autologous bone marrow transplantation (ABMT) . Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n = 166; Hodgkin's disease n = 38) were, after induction treatment with the DHAP-VIM (cisplatin, cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate) regimen, randomly (2:1) assigned to the harvest of granulocyte-macrophage colony-stimulating factor-mobilized stem cells after the second DHAP course or autologous bone marrow cells before the second DHAP course . These stem cells were reinfused following high-dose myeloblative chemotherapy . After induction, 118 patients obtained a partial or complete response and were eligible for randomization . In the PSCT arm (n = 76) significantly faster engraftment of neutrophils {> or = 0.1 and > or = 0.5 x 10(9)/l: 10.7 d (7-36, median, range), 15 (9-45) versus 13 (8-25) and 26 (14-80), P < 0.01} and thrombocytes {> or = 20 x 10(9)/l: 13 d (7-51) versus 18 (11-65), P < 0.01} were observed . In addition, significantly fewer transfusions of red blood cells {6 (0-23) versus 8 (2-24), P < 0.01} and platelets {4 (0-60) versus 8 (2-55), P = 0.01} were required in the PSCT arm . These findings were associated with a significant reduction in the median days of intravenous antibiotics in patients with fever {8.5 (0-30) versus 14 (0-34), P = 0.04} and hospital stay {27 (8-51) versus 34 (24-78), P < 0.05} . Quality of life demonstrated a significant difference in favour of the PSCT arm . Total transplantation costs were significantly lower in the PSCT arm {$13,954 ($4913- 29,532) versus $17 668 ($10,170-44,083) P < 0.05}, as a result of the reduced hospital stay and lower antibiotic costs . In summary, these results indicate that PSCT is superior to ABMT with regard to engraftment, supportive care, quality of life and cost.

Org Lett, 2001 Sep 6, 3(18), 2899 - 902
Concise synthesis of a lactonamycin model system by diastereoselective dihydroxylation of a highly functionalized naphthoquinone; Cox C et al.; {reaction: see text} . In this Letter, we describe an approach to the highly functionalized tetracycle 6, a model compound corresponding to the CDEF ring system contained in the recently discovered antibiotic lactonamycin . Our approach features an unprecedented, highly stereoselective dihydroxylation of quinone 13a, which leads directly to spirocyclic lactone 15, following acid-promoted deprotection/cyclization . The methodology described herein paves the way for a concise, highly diastereo- and enantioselective synthesis of the natural product.

Org Lett, 2001 Sep 6, 3(18), 2867 - 9
Analogues of bleomycin: synthesis of conformationally rigid methylvalerates; Rishel MJ et al.; {structure: see text} . Several conformationally rigid analogues of the methylvalerate subunit contained within the linker domain of the antitumor antibiotic bleomycin have been prepared . These compounds have been protected in a fashion suitable for the solid-phase synthesis of bleomycin . Bleomycin congeners containing these analogues should facilitate a more detailed understanding of the nature of the conformational bend that the methylvalerate moiety is thought to impart to the natural product.

Klin Padiatr, 2001 Jul-Aug, 213(4), 212 - 38
{Hematopoietic growth factors in prophylaxis and therapy of infections complications in children with neutropenia}; Lehrnbecher T; Hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures to reduce infectious complications associated with congenital or acquired 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 corpus 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-CSF or GM-CSF is recommended in a subset of pediatric cancer patients shortly after having received chemotherapy or a form of a marrow transplant . Children with highly intensive chemotherapy (e.g., children with high risk ALL or NHL) seem to benefit from hematopoietic growth factors whereas this is still unclear for children undergoing therapy for solid tumors . An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells for autologous or allogeneic transplantation . In pediatric patients with hematological diseases, there are only few data on the use of hematopoietic growth factors in children with myelodysplastic syndrome . Experts recommend the early administration of G-CSF in children with very severe aplastic anemia . The use of G-CSF is also recommended in children with severe chronic neutropenia, but these patients have to be monitored regularly for cytogenetic abnormalities . No larger study has shown a clinical benefit of hematopoietic growth factor in preterm or term infants . Future studies in pediatric 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 of patients . 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.

Dig Surg, 2001, 18(4), 283 - 8
Single and multiple pyogenic liver abscesses: etiology, clinical course, and outcome; Alvarez JA et al.; BACKGROUND: Pyogenic liver abscesses are uncommon but they still carry a high mortality rate when encountered . This study was undertaken to evaluate the differences in the clinical behaviour of patients with single and multiple abscesses . METHODS: From January 1985 to December 1997, 133 patients with this disease were treated in the surgical departments of five hospitals, 97 had a single abscess and 36 had multiple abscesses . Clinical features, methods of treatment, and outcome were assessed and compared in both types of abscesses . RESULTS: A biliary origin from ascending cholangitis was most frequently found in multiple abscesses (p = 0.007) . Mean age and duration of symptoms were higher in multiple lesions (p = 0.03 and p = 0.001) . High levels of alkaline phosphatase were more frequently seen in multiple abscesses than in solitary ones (p = 0.02) . They were both most frequently located on the right side . Antibiotic therapy alone was most frequently used in multiple abscesses (p = 0.01) . Mortality rate was also higher in this type of patients (p = 0.01) . The abscess-related morbidity rate was higher in multiple lesions as well but the statistical difference was not significant . CONCLUSIONS: These results suggest that multiple liver abscesses comprise a disease of biliary origin, higher age, longer symptomatic periods, and also higher mortality rate than in single abscess .

Microbiol Mol Biol Rev, 2001 Sep, 65(3), 463 - 79, table of contents
Autophagy in yeast: mechanistic insights and physiological function; Abeliovich H et al.; Unicellular eukaryotic organisms must be capable of rapid adaptation to changing environments . While such changes do not normally occur in the tissues of multicellular organisms, developmental and pathological changes in the environment of cells often require adaptation mechanisms not dissimilar from those found in simpler cells . Autophagy is a catabolic membrane-trafficking phenomenon that occurs in response to dramatic changes in the nutrients available to yeast cells, for example during starvation or after challenge with rapamycin, a macrolide antibiotic whose effects mimic starvation . Autophagy also occurs in animal cells that are serum starved or challenged with specific hormonal stimuli . In macroautophagy, the form of autophagy commonly observed, cytoplasmic material is sequestered in double-membrane vesicles called autophagosomes and is then delivered to a lytic compartment such as the yeast vacuole or mammalian lysosome . In this fashion, autophagy allows the degradation and recycling of a wide spectrum of biological macromolecules . While autophagy is induced only under specific conditions, salient mechanistic aspects of autophagy are functional in a constitutive fashion . In Saccharomyces cerevisiae, induction of autophagy subverts a constitutive membrane-trafficking mechanism called the cytoplasm-to-vacuole targeting pathway from a specific mode, in which it carries the resident vacuolar hydrolase, aminopeptidase I, to a nonspecific bulk mode in which significant amounts of cytoplasmic material are also sequestered and recycled in the vacuole . The general aim of this review is to focus on insights gained into the mechanism of autophagy in yeast and also to review our understanding of the physiological significance of autophagy in both yeast and higher organisms.

Hepatology, 2001 Sep, 34(3), 487 - 93
Increased production of vascular endothelial growth factor in peritoneal macrophages of cirrhotic patients with spontaneous bacterial peritonitis; Cejudo-Martin P et al.; Spontaneous bacterial peritonitis (SBP) is a common complication of cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy . The pathogenesis of these phenomena is poorly known but it has been related to the production of vasoactive cell mediators locally acting on the splanchnic vasculature . Because previous studies showed that peritoneal macrophages of cirrhotic patients may produce high quantities of vascular endothelial growth factor (VEGF), a powerful vessel permeabilizing agent, when stimulated by cytokines and bacterial lipopolysaccharide, the present study was aimed to seek whether peritoneal macrophages of SBP patients are induced to produce increased amounts of VEGF . Our results indicate that the production rate and the messenger RNA (mRNA) and protein expression of this substance are increased in macrophages of patients with SBP in comparison with those of noninfected cirrhotic patients . This characteristic feature is absent in circulating monocytes of these patients . Moreover, enhanced endothelial cell proliferation induced by conditioned medium of macrophages isolated from the ascites of patients with SBP is abolished by anti-VEGF antibody, and peritoneal tissue of cirrhotic patients expresses both VEGF receptors, Flt-1 and KDR . These results, therefore, are consistent with the concept that locally released macrophage-derived VEGF may result in increased vascular permeability and plasma leakage in the peritoneal vessels of cirrhotic patients with SBP.

J Clin Microbiol, 2001 Sep, 39(9), 3213 - 21
Use of serum immune complexes in a new test that accurately confirms early Lyme disease and active infection with Borrelia burgdorferi; Brunner M et al.; The present recommendation for serologic confirmation of Lyme disease (LD) calls for immunoblotting in support of positive or equivocal ELISA . Borrelia burgdorferi releases large quantities of proteins, suggesting that specific antibodies in serum might be trapped in immune complexes (ICs), rendering the antibodies undetectable by standard assays using unmodified serum . Production of ICs requires ongoing antigen production, so persistence of IC might be a marker of ongoing or persisting infection . We developed an immunoglobulin M (IgM) capture assay (EMIBA) measuring IC-derived IgM antibodies and tested it using three well-defined LD populations (from an academic LD referral center, a well-described Centers for Disease Control and Prevention (CDC) serum bank, and a group of erythema migrans patients from whose skin lesions B . burgdorferi was grown) and controls (non-Lyme arthritis inflammatory joint disease, syphilis, multiple sclerosis, and nondisease subjects from a region where LD is endemic, perhaps the most relevant comparison group of all) . Previous studies demonstrated that specific antigen-antibody complexes in the sera of patients with LD could be precipitated by polyethylene glycol and could then be disrupted with maintenance of the immunoreactivity of the released antibodies, that specific anti-B . burgdorferi IgM was concentrated in ICs, and that occasionally IgM to specific B . burgdorferi antigens was found in the IC but not in unprocessed serum . EMIBA compared favorably with commercial and CDC flagellin-enhanced enzyme-linked immunosorbent assays and other assays in confirming the diagnosis of LD . EMIBA confirmed early B . burgdorferi infection more accurately than the comparator assays . In addition, EMIBA more accurately differentiated seropositivity in patients with active ongoing infection from seroreactivity persisting long after clinically successful antibiotic therapy; i.e., EMIBA identified seroreactivity indicating a clinical circumstance requiring antibiotic therapy . Thus, EMIBA is a promising new assay for accurate serologic confirmation of early and/or active LD.

J Am Chem Soc, 2001 Sep 5, 123(35), 8515 - 9
Asymmetric total synthesis of ent-(-)-roseophilin: assignment of absolute configuration; Boger DL et al.; An asymmetric total synthesis of ent-(-)-roseophilin (1), the unnatural enantiomer of a novel naturally occurring antitumor antibiotic, is described . The approach enlists a room temperature heterocyclic azadiene inverse electron demand Diels-Alder reaction of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (7) with the optically active enol ether 6 bearing the C23 chiral center followed by a reductive ring contraction reaction for formation of an appropriately functionalized pyrrole ring in a key 1,2,4,5-tetrazine --> 1,2-diazine --> pyrrole reaction sequence . A Grubbs' ring closing metathesis reaction was utilized to close the unusual 13-membered macrocycle prior to a subsequent 5-exo-trig acyl radical-alkene cyclization that was used to introduce the fused cyclopentanone and complete the preparation of the tricylic ansa-bridged azafulvene core 32 . Condensation of 32 with 33 under the modified conditions of Tius and Harrington followed by final deprotection provided (22S,23S)-1 . Comparison of synthetic (22S,23S)-1 ({alpha}(25)(D), CD) with natural 1 established that they were enantiomers and enabled the assignment of the absolute stereochemistry of the natural product as 22R,23R . Surprisingly, ent-(-)-1 was found to be 2-10-fold more potent than natural (+)-1 in cytotoxic assays, providing an unusually rewarding culmination to synthetic efforts that provided the unnatural enantiomer.

Clin Microbiol Infect, 2001, 7 Suppl 2, 1 - 7
Changing spectrum of invasive candidiasis and its therapeutic implications; Singh N; Emerging trends in invasive candidiasis are notable for a dramatic increase in infections due to non-albicans Candida species . An increasing number of immunocompromised patients at risk from fungal infections, an overall greater acuity of illness in the hospitalized patients, particularly those in the critical care units, escalating rates of broad-spectrum antibiotic usage, and wide utilization of azoles as prophylaxis have probably contributed towards the changing epidemiology of invasive candidiasis . Given the inherent decreased susceptibility of many of the non-albicans Candida species to currently available antifungal agents, these evolving trends have far-reaching clinical relevance.

Arch Intern Med, 2001 Aug 13-27, 161(15), 1837 - 42
Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia; Waterer GW et al.; BACKGROUND: Although monotherapy for pneumococcal pneumonia is standard, a survival benefit of combination beta-lactam and macrolide therapy has been suggested . HYPOTHESIS: Initial empirical therapy with a combination of effective antibiotic agents would have a better outcome than a single effective antibiotic agent in patients with bacteremic pneumococcal pneumonia . METHODS: A review of adult bacteremic pneumococcal pneumonia within the Methodist Healthcare System, Memphis, Tenn, between January 1, 1996, and July 31, 2000 . Empirical therapy was defined as all antibiotic agents received in the first 24 hours after presentation . On the basis of culture results, empirical therapy was classified as single effective therapy (SET), dual effective therapy (DET), or more than DET (MET) . Acute Physiology and Chronic Health Evaluation II (APACHE II)-based predicted mortality, and Pneumonia Severity Index scores were calculated . RESULTS: Of the 225 patients identified, 99 were classified as receiving SET, 102 as receiving DET, and 24 as receiving MET . Compared with the other groups, patients who received MET had statistically significantly more severe pneumonia as measured by the Pneumonia Severity Index score (P =.04) and predicted mortality (P =.03) . Mortality within the SET group was significantly higher than within the DET group (P =.02, odds ratio, 3.0 {95% confidence intervals, 1.2-7.6}), even when the DET and MET groups (P =.04) were combined . In a logistic regression model including antibiotic therapy and clinical risk factors for mortality, SET remained an independent predictor of mortality with a predicted mortality-adjusted odds ratio for death of 6.4 (95% confidence intervals, 1.9-21.7) . All deaths occurred in patients with a Pneumonia Severity Index score higher than 90, and the predicted mortality-adjusted odds ratio for death with SET in this subgroup was 5.5 (95% confidence intervals, 1.7-17.5) . CONCLUSIONS: We found that SET is associated with a significantly greater risk of death than DET . Therefore, monotherapy may be suboptimal for patients with severe bacteremic pneumococcal pneumonia who have Pneumonia Severity Index scores higher than 90.

Biochemistry, 2001 Sep 4, 40(35), 10473 - 84
Solution structure of a guanine-N7-linked complex of the mitomycin C metabolite 2,7-diaminomitosene and DNA . Basis of sequence selectivity; Subramaniam G et al.; 2,7-Diaminomitosene (2,7-DAM), the major metabolite of the antitumor antibiotic mitomycin C, forms DNA adducts in tumor cells . 2,7-DAM was reacted with the deoxyoligonucleotide d(GTGGTATACCAC) under reductive alkylation conditions . The resulting DNA adduct was characterized as d(G-T-G-{M}G-T-A-T-A-C-C-A-C) (5), where {M}G stands for a covalently modified guanine, linked at its N7-position to C10 of the mitosene . The adducted oligonucleotide complements with itself, retaining 2-fold symmetry in the 2:1 drug-duplex complex, and provides well-resolved NMR spectra, amenable for structure determination . Adduction at the N7-position of G4 ({M}G, 4) is characterized by a downfield shift of the G4(H8) proton and separate resonances for G4(NH(2)) protons . We assigned the exchangeable and nonexchangeable proton resonances of the mitosene and the deoxyoligonucleotide in adduct duplex 5 and identified intermolecular proton-proton NOEs necessary for structural characterization . Molecular dynamics computations guided by 126 intramolecular and 48 intermolecular distance restraints were performed to define the solution structure of the 2,7-DAM-DNA complex 5 . A total of 12 structures were computed which exhibited pairwise rmsd values in the 0.54-1.42 A range . The 2,7-DAM molecule is anchored in the major groove of DNA by its C10 covalently linked to G4(N7) and is oriented 3' to the adducted guanine . The presence of 2,7-DAM in the major groove does not alter the overall B-DNA helical structure . Alignment in the major groove is a novel feature of the complexation of 2,7-DAM with DNA; other known major groove alkylators such as aflatoxin, possessing aromatic structural elements, form intercalated complexes . Thermal stability properties of the 2,7-DAM-DNA complex 5 were characteristic of nonintercalating guanine-N7 alkylating agents . Marked sequence selectivity of the alkylation by 2,7-DAM was observed, using a series of oligonucleotides incorporating variations of the 5'-TGGN sequence as substrates . The selectivity correlated with the sequence specificity of the negative molecular electrostatic potential of the major groove, suggesting that the alkylation selectivity of 2,7-DAM is determined by sequence-specific variation of the reactivity of the DNA . The unusual, major groove-aligned structure of the adduct 5 may account for the low cytotoxicity of 2,7-DAM.

J Trop Pediatr, 2001 Aug, 47(4), 230 - 8
Treatment of childhood fevers and other illnesses in three rural Nigerian communities; Salako LA et al.; The seeking of healthcare for childhood illnesses was studied in three rural Nigerian communities of approximately 10,000 population each . The aim was to provide a baseline understanding of illness behaviour on which to build a programme for the promotion of prepackaged chloroquine and cotrimoxazole for early and appropriate treatment of childhood fevers at the community level . A total of 3117 parents of children who had been ill during the 2 weeks prior to interview responded to questions about the nature of the illness and the actions taken . Local illness terms were elicited, and the most prevalent recent illness and the actions taken . Local illness terms were elicited, and the most prevalent recent illnesses were 'hot body' (43.9 per cent), malaria, known as iba (17.7 per cent), and cough (7.4 per cent) . The most common form of first-line treatment was drugs from a patent medicine vendor or drug hawker (49.6 per cent) . Only 3.6 per cent did nothing . Most who sought care (77.5 per cent) were satisfied with their first line of action, and did not seek further treatment . The average cost of an illness episode was less than US$2.00 with a median of US$1.00 . Specifically, chloroquine tablets cost an average of US 29 cents per course . Analysis found a configuration of signs and symptoms associated with chloroquine use, to include perception of the child having malaria, high temperature and loss of appetite . The configuration positively associated with antibiotic use consisted of cough and difficult breathing . The ability of the child's care-givers, both parental and professional, to make these distinctions in medication use will provide the foundation for health education in the promotion of appropriate early treatment of childhood fevers in the three study sites.

Gastrointest Endosc, 2001 Sep, 54(3), 368 - 72
Combined antegrade and retrograde dilation: a new endoscopic technique in the management of complex esophageal obstruction; Bueno R et al.; BACKGROUND: Esophageal strictures that cause complete obstruction are often difficult to dilate with standard bougienage techniques . METHODS: A new technique was developed and applied, combined antegrade and retrograde dilation, for dilatation of complex esophageal strictures . The stomach is accessed and an endoscope (9.8 mm diameter) is directed under fluoroscopy in a retrograde fashion into the distal esophagus . A guidewire with a hydrophilic coating is advanced through the stricture and then pulled through the mouth with a simultaneously placed proximal endoscope . The guidewire is then used as a guide for antegrade esophageal dilatation . RESULTS: Ten patients with complex esophageal strictures (with and without fistulas) were treated with this technique . Three required a second combined antegrade and retrograde dilation procedure . All strictures were dilated and no perforations occurred . CONCLUSIONS: Combined antegrade and retrograde dilation is a safe and effective technique for dilation of complex obstructing esophageal lesions.

Anal Biochem, 2001 Sep 1, 296(1), 101 - 5
A fluorometric assay for the determination of 1-deoxy-D-xylulose 5-phosphate synthase activity; Querol J et al.; We report a novel fluorometric end-point assay for the determination of 1-deoxy-d-xylulose 5-phosphate synthase (DXS) activity based on the reaction of 1-deoxy-D-xylulose 5-phosphate (DX5P) with 3,5-diaminobenzoic acid in an acidic medium to form a highly fluorescent quinaldine derivative . The assay was validated in three ways: (a) for a fixed amount of DXS in the reaction mixture the emitted fluorescence increased linearly with the reaction time, (b) for a fixed reaction time fluorescence intensity increased with the concentration of DXS in the reaction mixture, and (c) the increase in fluorescence intensity correlated (r = 0.99; P < 0.002) with the amount of DX5P formed in the reaction mixture determined radiometrically . The sensitivity of the fluorometric assay is similar to that of the previously described radiometric methods . This assay can be useful for the functional characterization of DXS as well as for the screening of DXS inhibitors with potential antibiotic, herbicidal, or antimalarial action .

Acta Paediatr, 2001 Jul, 90(7), 757 - 64
Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original "Kostmann family" and a review; Carlsson G et al.; In 1956 Rolf Kostmann reported on six children with severe neutropenia associated with a block in myelopoiesis at the promyelocyte/myelocyte stage and an autosomal recessive inheritance . He named the new syndrome infantile genetic agranulocytosis . Today it is known as Kostmann's syndrome or severe congenital neutropenia . In 1975 an additional 10 cases from northern Sweden were published . This article reports on the only long-term survivor from the 1975 report plus another five patients born after 1975 who belong to the original "Kostmann family" . Treatment and survival have changed dramatically since Kostmann's first publication . In the pre-antibiotic era, Kostmann's syndrome was inevitably fatal during the first year of life . CONCLUSION: Since the introduction of recombinant human granulocyte colony-stimulating factor (G-CSF) about 10 y ago, most patients now enjoy a normal life span and a greatly improved quality of life . Although the threat of death has disappeared, patients still have problems with infections, especially chronic gingivitis and periodontitis . In other groups of severe neutropenia, not related to the original "Kostmann family", an increased incidence of myeloid leukaemia has been observed . However, in this small cohort none of the children on chronic G-CSF therapy have developed malignancies.

Infect Control Hosp Epidemiol, 2001 Jun, 22(6), 347 - 51
Factors associated with postoperative infection; Scott JD et al.; OBJECTIVE: We have developed and analyzed a large surgical prophylaxis database and now report the factors significantly associated with early infection, readmission due to infection, and death within 28 days of surgery . This study is intended to be a stepping-stone for further studies using our clinical database . DESIGN AND SETTING: A computerized database of 9,016 surgical patients from a 400-bed community hospital was examined . Multivariate logistic regression and tree-based modeling were used to identify factors associated with the outcomes . Factors considered included surgical procedure, prophylactic antibiotic, age, gender, serum creatinine, and albumin . RESULTS: 12.6% had an early infection, 2.5% were readmitted due to infection, and 2.5% died within 28 days . Most combination prophylactic antibiotics were associated with an increased probability of an early infection . Decreased albumin and increased age were associated with an increased probability of an early infection . Tracheostomy and amputations were associated with an increased probability of an early infection, whereas gallbladder and orthopedic procedures involving the arm were associated with a decreased probability . Factors associated with readmission due to infection included dialysis shunt, vascular repair, and an early infection . Factors associated with increased probability of death within 28 days included age, albumin, serum creatinine, and an early infection . Gallbladder procedures and obstetric-gynecologic procedures were associated with a decreased probability of death within 28 days . DISCUSSION: Older patients and those with a decreased albumin were most likely to have an early infection . To the extent that an early infection was a significant risk factor for readmission due to infection, the impact of age and albumin on the probability of readmission due to infection is demonstrated by their effects on early infections . Interestingly, albumin and age were significantly associated with death within 28 days, in addition to early infection, showing the predictive association between these factors and early death.

J Mol Biol, 2001 Aug 24, 311(4), 777 - 87
Localization of L11 protein on the ribosome and elucidation of its involvement in EF-G-dependent translocation; Agrawal RK et al.; L11 protein is located at the base of the L7/L12 stalk of the 50 S subunit of the Escherichia coli ribosome . Because of the flexible nature of the region, recent X-ray crystallographic studies of the 50 S subunit failed to locate the N-terminal domain of the protein . We have determined the position of the complete L11 protein by comparing a three-dimensional cryo-EM reconstruction of the 70 S ribosome, isolated from a mutant lacking ribosomal protein L11, with the three-dimensional map of the wild-type ribosome . Fitting of the X-ray coordinates of L11-23 S RNA complex and EF-G into the cryo-EM maps combined with molecular modeling, reveals that, following EF-G-dependent GTP hydrolysis, domain V of EF-G intrudes into the cleft between the 23 S ribosomal RNA and the N-terminal domain of L11 (where the antibiotic thiostrepton binds), causing the N-terminal domain to move and thereby inducing the formation of the arc-like connection with the G' domain of EF-G . The results provide a new insight into the mechanism of EF-G-dependent translocation .

Eur J Contracept Reprod Health Care, 2001 Jun, 6(2), 115 - 26
Chlamydia trachomatis infections--a major concern for reproductive health . Where do we stand regarding epidemiology, pathogenesis, diagnosis and therapy?
Mardh PA, Novikova N.
The current article deals with the problem of distinguishing between relapse and reinfection of genital chlamydial infections due to the chronic character of such infections . The problem of detecting and treating chlamydial pelvic inflammatory disease is considered . Factors that may affect the clinical presentation of such infections, such as hormonal therapy, are also highlighted . Observations on novel manifestations of Chlamydia trachomatis infections, such as spontaneous abortion, prematurity and intrauterine infections as well as a statistical correlation of a certain serovar to cervical cancer, are described . The representivity of the data on infections with C . trachomatis monitored in national surveillance programs is questioned . The paper also elaborates on which type of sample, sample site and detection method may be optimal for the diagnosis of such infections in women . Whether to screen at clinics and self-sampling at home of specimens from an index case and a sexual partner to be mailed to a laboratory for testing is discussed . Whether or not females are more susceptible to genital chlamydial infections and their sequelae than males is also discussed . The effectiveness of recommended antibiotic regimens is considered, e.g . in relation to the recent detection of the existence of strains of C . trachomatis that show heterotypic resistance to drugs commonly used for their treatment.

Genetika, 2001 Jun, 37(6), 784 - 90
{Inheritance of altered flower morphology and kanamycin resistance in transgenic Tobacco plants}; Zagorskaia AA et al.; Inheritance of altered flower morphology and resistance to antibiotic kanamycin was studied in the first and second generations (T1 and T2, respectively) of self-pollinated transgenic tobacco plants . In most transformants, kanamycin resistance was closely linked to mutant phenotype . T-DNA-induced mutations were shown to be dominant.

Curr Opin Clin Nutr Metab Care, 2001 May, 4(3), 211 - 8
Evidence-based prevention of catheter infection during parenteral nutrition; Attar A et al.; Parenteral nutrition is a risk factor for catheter-related bloodstream infection . Here we reviewed strategies for the prevention of catheter-related infections, which always must begin with the cornerstone of prevention: the strict adherence to aseptic techniques . Most research has been interested in coated catheters . From these results, it may be concluded that antibiotics or antiseptic-impregnated catheters, like those with minocycline-rifampicin or chlorhexidine/silver sulfadiazine, significantly reduce catheter-related blood stream infections . Antibiotics or antiseptic-impregnated central venous catheters may even result in cost saving in intensive care units . Antiseptic or antibiotic-lock techniques would also be of interest to prevent catheter-related sepsis in high-risk patients who are receiving parenteral nutrition.

Proc Natl Acad Sci U S A, 2001 Sep 11, 98(19), 10775 - 80 Epub 2001 Aug 21.
Tetracycline-inducible systems for Drosophila; Stebbins MJ et al.; Since their inception, tetracycline (Tet)-inducible systems have become the method of choice for transgenic research . The Tet-Off systems have a number of advantages, including robust target induction using a relatively benign effector molecule . However, use of the Tet-On system has been fraught with difficulties, including high background expression in the absence of effector molecules and inconsistent gene induction . Recently, second generation Tet-On transactivators (TAs) have been described . In HeLa cells, they are far more efficient than the original reverse TA protein, and they exhibit lower background activity in the absence of effectors . Here we examine the most promising TA in transgenic Drosophila and characterize its in vivo properties . We report that low levels of doxycycline, when added to normal fly food, efficiently and rapidly induce target transgenes in adults, larvae, and embryos . This TA is superior to all other Tet-On proteins, and its performance is comparable to that of the widely used Tet-Off TA . In addition, combining the improved Tet-On TA with the Gal4-UAS (upstream-activating sequence) system produces robust, spatially restricted, temporally controlled transgene induction . Because this Tet-On TA is significantly more efficient than previous ones used in Drosophila, it is also possible to modulate gene induction by controlling the dosage of the antibiotic in the food.

J Hosp Infect, 2001 Sep, 49(1), 4 - 8
Infection prevention in necrotizing pancreatitis: an old challenge with new perspectives; Butturini G et al.; Necrotizing pancreatitis still remains a life-threatening disease despite several improvements in diagnosis, prevention and treatment . In recent years, some important questions have been answered such as the need for early intensive medical treatment rather than early surgery, but others are still strongly debated . The aim of this paper is to present an up-to-date assessment of current challenges in the management of necrotizing pancreatitis in order to prevent infection .

Scand J Infect Dis, 2001, 33(7), 551 - 3
Intra-abdominal actinomycosis with hepatic pseudotumor and xanthogranulomatous pyelonephritis in a 6-y-old boy; Lin TP et al.; We report the case of a 6-y-old boy with actinomycosis, presenting as xanthogranulomatous pyelonephritis (XGP), hepatic pseudotumor and abdominal abscess . Symptoms included intermittent fever, abdominal pain and significant weight loss . Hepatic and renal tumor masses were suspected on sonography and computerized tomography . XGP and actinomycosis were proven by pathology . The patient recovered well with antibiotic alone.

G Chir, 2001 Jun-Jul, 22(6-7), 235 - 7
{Fournier syndrome: report of a clinical case}; La Torre F et al.; The case of a Fournier's syndrome in a 58 years old patient is reported from the Authors that describe the ethiopathogenetic and therapeutic aspects . They analyse the importance of an early surgical treatment associated with antibiotic therapy and later a riparation of the lesions with a myocutaneous skin flap of TLF.

Hong Kong Med J, 2001 Jun, 7(2), 197 - 200
Porphyria cutanea tarda and melioidosis; Fung WK et al.; Porphyria cutanea tarda is a metabolic disorder in the haem biosynthetic pathway . It includes a heterogeneous group of conditions, which may be inherited or, more commonly, acquired . Although porphyria cutanea tarda presents with cutaneous lesions only, it is often associated with systemic disease . A 64-year-old Chinese patient, who developed sporadic porphyria cutanea tarda 1 year after the diagnosis of pulmonary melioidosis, is discussed . The patient presented with a history of recurrent photosensitive vesicles, blisters, and skin fragility on the sun-exposed areas of both forearms and hands, 6 months after commencing doxycycline and amoxycillin . Both the histological and biochemical findings were characteristic of porphyria cutanea tarda . All the lesions subsided after cessation of these antibiotics . The patient was free of further lesions at follow-up 6 months later . The association seen in this case between porphyria cutanea tarda and melioidosis is unlikely to be coincidental, because these two diseases are both very rare in Hong Kong . In addition, the temporal relationship between the antibiotic therapy and the clinical course of skin lesions in this patient suggests that the drugs were a trigger factor, precipitating their appearance.

Biochim Biophys Acta, 2001 Sep 3, 1528(1), 15 - 24
MFAME, N-methyl-N-D-fructosyl amphotericin B methyl ester, a new amphotericin B derivative of low toxicity: relationship between self-association and effects on red blood cells; Szlinder-Richert J et al.; In aqueous solutions N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME), a novel amphotericin B derivative with low animal toxicity, similar to its parent antibiotic, exists in three forms: monomeric, soluble and insoluble aggregates in equilibrium {1} . The aim of our work was to examine the influence of medium composition on the MFAME self-association and the relationship between MFAME self-association and its toxicity towards red blood cells . The toxicity of MFAME in aggregated state towards red blood cells was tested by measuring the induction of potassium leakage and extent of haemolysis . The proportions of antibiotic species present in various aqueous media were determined by analysis of the UV-Vis spectra as a function of the antibiotic concentration . Numeric decomposition of the spectra allowed identification of four spectral species present in MFAME solutions: monomeric and three aggregated forms . Our results indicate that these aggregates, named type I, type II and type III, are different in terms of spectral properties, as well as effectiveness towards red blood cells . Soluble aggregate types I and III are the active forms of MFAME towards erythrocytes . The medium composition seems to be the main factor determining which type of antibiotic aggregate prevails in solution.

In Vitro Cell Dev Biol Anim, 2001 May, 37(5), 293 - 302
Stable cell lines expressing baculovirus P35: resistance to apoptosis and nutrient stress, and increased glycoprotein secretion; Lin G et al.; The baculovirus P35 protein is a caspase inhibitor that prevents the induction of apoptosis during infection of Sf21 cells by Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) . P35 inhibits the induction of apoptosis in a broad range of cells and circumstances . In this study, we examined the effects of constitutive cellular P35 expression on the response of cells to stressful culture conditions and on protein production in AcMNPV infected cells . Sf9 cell lines expressing AcMNPV P35 or an epitope-tagged P35 protein were generated using a double selection technique, involving selection in the antibiotic G418, followed by a second round of selection by exposure to actinomycin D, a potent inducer of apoptosis in Sf9 cells . Clonal cell lines were generated and examined for (1) resistance to actinomycin D induced apoptosis, (2) resistance to nutrient deprivation, and (3) baculovirus expression of intracellular and secreted proteins . When compared with Sf9 cells, two P35-expressing cell lines (Sf9P35AcV5-1 and Sf9P35AcV5-3) showed increased resistance to actinomycin D-induced apoptosis and a profound resistance to nutrient deprivation . When these cell lines were infected with a recombinant baculovirus expressing a secreted glycoprotein (secreted alkaline phosphatase), expression of the glycoprotein from these cells exceeded that from the parental Sf9 cells and was comparable to expression levels obtained from Tn5B1-4 cells, the best available cell line for high-level expression . Increased levels of protein secretion in Sf9P35AcV5-1 and Sf9P35AcV5-3 cells appear to result from a prolonged infection cycle and accumulation of the secreted glycoprotein.

J Antibiot (Tokyo), 2001 Jun, 54(6), 501 - 5
Association of induced disease resistance of rhododendron seedlings with inoculation of Streptomyces sp . R-5 and treatment with actinomycin D and amphotericin B to the tissue-culture medium; Shimizu M et al.; Seedlings of rhododendron were treated by adding Streptomyces sp . strain R-5, actinomycin D and/or amphotericin B to the tissue-culture medium . HPLC analysis showed that all of the treated seedlings contained these antibiotics at concentrations higher than the suppressive levels to mycelial growth of Pestalotiopsis sydowiana, a major pathogen of rhododendron . Occurrence of disease caused by this fungus in the seedlings was suppressed by treatment of the medium surface with strain R-5, but not by treatment with these antibiotics, suggesting that growth of strain R-5, an antibiotic producer, could be essential for induction of disease resistance in tissue-cultured seedlings of rhododendron.

Surg Today, 2001, 31(8), 675 - 7
The management of appendiceal mass in children: is interval appendectomy necessary?
Karaca I, Altintoprak Z, Karkiner A, Temir G, Mir E.
In this study we aimed to show that performing interval appendectomy is unnecessary in the management of appendiceal mass in children . Between 1990 and 1996, 866 patients were treated for appendicitis . Abdominal ultrasonography (USG) was performed in patients who were admitted with abdominal pain, vomiting, and fever accompanying a mass in the right lower quadrant . Seventeen patients (12 boys and 5 girls, with a mean age of 9.5 years) with a mass in the appendiceal lodge and no abscess formation were treated conservatively . Appendectomy was performed on any patients with perforated or unperforated appendicitis who had an appendiceal abscess with a mass in the right iliac fossa . Three-agent antibiotic therapy was administered for at least 1 week . These patients were discharged after a mean hospital time of 9.7 days if regression of the mass was seen ultrasonographically . They were followed up for 1-60 months by physical examination and USG, and 11 of the 17 also underwent barium enema . USG demonstrated disappearance of the mass and barium enema showed a normal appendix in 10 of the 11 patients . No recurrent appendicitis was detected during follow-up for 1-7 years . This study shows that appendiceal masses that are perforated, but localized with no fluid content revealed by USG, can be treated conservatively even if they are detected late.

Liver Transpl, 2001 Aug, 7(8), 739 - 42
The effect of selective bowel decontamination on the pharmacokinetics of mycophenolate mofetil in liver transplant recipients; Schmidt LE et al.; Mycophenolate mofetil (MMF) is a prodrug immunosuppressant with a high oral bioavailability . Enterohepatic cycling of a glucuronide derivative of MMF contributes substantially to the bioavailability, but is dependent on bacterial deglucuronidation by intestinal flora . This study aims to determine whether an antibiotic regimen with activity against such organisms reduces the bioavailability of MMF by impairing enterohepatic cycling . In a prospective trial, 6 liver transplant recipients were administered MMF and a 21-day antibiotic regimen for selective bowel decontamination (SBD) . Time-concentration profiles of the pharmacologically active metabolite, mycophenolic acid (MPA), were obtained during and after the SBD regimen . The bioavailability of MPA was reduced during compared with after the regimen (14.5 +/- 3.5 v 21.1 +/- 9.8 mg . h/mL; P =.07) . The most pronounced contribution to this reduction was observed from 6 hours onward (2.4 +/- 1.4 v 5.6 +/- 4.4 mg . h/mL; P <.05) . The presence of secondary maxima in the time-concentration profiles of MPA after, but not during, SBD indicates that enterohepatic cycling may be inhibited during SBD and restored afterward . Enterohepatic cycling may contribute 7% to 54% (mean, 29%) of the bioavailability of MPA . We conclude that the bioavailability of MMF may be reduced when SBD is used, and the reduction is likely to result from the interruption of enterohepatic cycling . This mechanism should be taken into consideration not only during SBD, but in any clinical setting combining MMF and broad-spectrum antibiotics.

Biophys J, 2001 Sep, 81(3), 1684 - 98
Conformation of alamethicin in oriented phospholipid bilayers determined by (15)N solid-state nuclear magnetic resonance; Bak M et al.; The conformation of the 20-residue antibiotic ionophore alamethicin in macroscopically oriented phospholipid bilayers has been studied using (15)N solid-state nuclear magnetic resonance (NMR) spectroscopy in combination with molecular modeling and molecular dynamics simulations . Differently (15)N-labeled variants of alamethicin and an analog with three of the alpha-amino-isobutyric acid residues replaced by alanines have been investigated to establish experimental structural constraints and determine the orientation of alamethicin in hydrated phospholipid (dimyristoylphosphatidylcholine) bilayers and to investigate the potential for a major kink in the region of the central Pro(14) residue . From the anisotropic (15)N chemical shifts and (1)H-(15)N dipolar couplings determined for alamethicin with (15)N-labeling on the Ala(6), Val(9), and Val(15) residues and incorporated into phospholipid bilayer with a peptide:lipid molar ratio of 1:8, we deduce that alamethicin has a largely linear alpha-helical structure spanning the membrane with the molecular axis tilted by 10-20 degrees relative to the bilayer normal . In particular, we find compatibility with a straight alpha-helix tilted by 17 degrees and a slightly kinked molecular dynamics structure tilted by 11 degrees relative to the bilayer normal . In contrast, the structural constraints derived by solid-state NMR appear not to be compatible with any of several model structures crossing the membrane with vanishing tilt angle or the earlier reported x-ray diffraction structure (Fox and Richards, Nature . 300:325-330, 1982) . The solid-state NMR-compatible structures may support the formation of a left-handed and parallel multimeric ion channel.

Toxicol Appl Pharmacol, 2001 Aug 15, 175(1), 10 - 8
Acute exposure of cerebellar granule neurons to ethanol suppresses stress-activated protein kinase-1 and concomitantly induces AP-1; Acquaah-Mensah GK et al.; The current studies were designed to examine the mechanisms of acute effects of ethanol on cerebellar granule neurons (CGNs) during neurodevelopment, with specific reference to activator protein-1 (AP-1) . CGNs, isolated from 3-day-old Sprague-Dawley rats and cultured for 3 days, were exposed to 0, 22.5, and 100 mM ethanol for 1 h . Gel shift assays performed on the nuclear protein extracts showed increased AP-1 and heat shock factor-1 (HSF-1) transcriptional activation in response to ethanol . Western blots and RT-PCR showed increased c-JUN and phosphorylated c-JUN (serine 73) protein, as well as c-jun mRNA . Ethanol paradoxically decreased the activity of stress-activated protein kinase-1 (SAPK-1) while increasing p44 and p42 mitogen-activated protein kinase (MAPK) activity . The protein synthesis-inhibiting and SAPK-1 activity-inducing antibiotic, anisomycin (30 and 500 microM) decreased AP-1 transcriptional activation to 47 and 23% of control values, respectively . The anisomycin effect was enhanced in the presence of 100 mM ethanol . Similarly, cycloheximide decreased ethanol-induced AP-1 transcriptional activation . Pretreatment with the MAPK kinase (MEK) pathway inhibitor PD98059 resulted in decreases in both ethanol-induced and control AP-1 DNA binding . Thus this acute ethanol-induced increased AP-1 transcriptional activation requires protein synthesis and involves MEK-independent increased MAPK phosphorylation, on the one hand, and decreased SAPK-1 activity on the other . The ethanol effect is thus ascribed to the activities of alternate kinase pathways and/or the inhibition of (a) protein phosphatase(s) . Exposure of CGNs to ethanol for 24 h resulted in decreased AP-1 DNA binding, an observation that could have consequences for overall neuronal function under chronic exposure conditions .

Probl Tuberk, 2001, (3), 34 - 6
{Effects of the enterosorbent SUMS-1 on isoniazid pharmacokinetics and lipid peroxidation in patients with pulmonary tuberculosis and drug-induced hepatic lesions}; Kolpakova TA et al.; The use of the enterosorbent SUMS-1 in the combined therapy for pulmonary tuberculosis patients with drug-induced toxic hepatic lesion arrests the clinical and laboratory manifestations of endotoxicosis, removes antibiotic intolerance, increases the elimination rate of isoniazid, and reduces its distribution scope, the area beneath the kinetic curve being unchanged . The plasma concentrations of primary products and after-products of lipid peroxidation products during enterosorbent therapy decline and the levels of ceruloplasmin and alpha-tocopherol remain unchanged.

Ther Umsch, 2001 Jul, 58(7), 425 - 34
{Eleven years of experience with permanently implanted port-systems in 329 cancer patients}; Coco O et al.; Intravenous port-systems are predominantly used for long-term chemotherapy in oncology . 164 of our patients were implanted with a Port-a-Cath and 165 patients with a Chemosite system . Indications, the duration of implantation, the duration of use, the access and complications were analysed . This retrospective study analyses 329 tumor patients, who have been treated at the Cancer Center Klinik im Park from September 1987 until February 1998 . The preferred access of implantation were: v . subclavia (47%) and v . cephalica (35%) . The average duration of implantation was 279 days for the Port-a-Cath system and 443 days for the Chemosite system . The most frequent complication immediately following surgery was a pneumothorax in 4% of the patients . The frequency of late complications was: thromboses 2%, infections 4% . This study analyses our experiences with fully implantable permanent intravenous catheter-systems in 329 tumor patients . These catheters can be used for very long periods with a low rate of complications.

Eur J Gastroenterol Hepatol, 2001 Aug, 13(8), 971 - 2
Hepatic abscesses complicating injection sclerotherapy of haemorrhoids; Murray-Lyon IM et al.; We report the case of a 50-year-old man who developed a febrile illness four days after injection sclerotherapy of his haemorrhoids . The patient increasingly became unwell and was eventually found to have multiple hepatic abscesses . He made a complete recovery with antibiotic therapy . The importance of educating both patients and doctors about this complication is emphasized.

Cancer Res, 2001 Aug 15, 61(16), 6255 - 63
Induction of transplantable mouse renal cell cancers by streptozotocin: in vivo growth, metastases, and angiogenic phenotype; Gruys ME et al.; Interleukin-2-based regimens of biological therapy have shown some clinical promise for the treatment of kidney cancer in humans, although the mechanisms responsible for tumor regression occurring in these patients remain unclear . Preclinical insight into these mechanisms is limited by a paucity of orthotopic animal models of kidney cancer . We have used streptozotocin, an antibiotic and diabetogenic nitrosamine compound derived from Streptomyces achromogenes to induce new kidney tumors in BALB/c mice . Single or multiple doses of streptozotocin induced kidney tumors in up to 25% of mice by 50-90 weeks of age, with up to 18% characterized as renal cell carcinomas (RCCs) . Several transplantable lines were obtained from the RCCs, and one of these lines was subsequently cloned . The initial tumor isolates and sublines were histologically reconfirmed to be RCCs, and all grew progressively but slowly (mean survival times, 57 to >100 days) in vivo after intrarenal implant . None of the primary isolates or sublines revealed mutations in either the VHL or Ras genes, although karyotype analysis and chromosome painting revealed the consistent presence of a submetacentric chromosome resulting from the fusion of chromosomes 16 and 19 . Biological characterization of these tumors revealed several features analogous to the growth of human kidney cancers, including a propensity for the formation of lung metastases and high vascularity . This hypervascularity is evident by both gross and microscopic analysis and correlates with the expression of several proangiogenic genes . Overall, the features of orthotopic transplantability, slower in vivo growth (relative to the rapid growth rates of other transplantable mouse kidney tumors), propensity for lung metastases, and hypervascularity may make these tumors valuable models for the study of new therapeutic strategies based on antineovascular agents and antitumor cytokines.

Mol Cell Biochem, 2001 May, 221(1-2), 25 - 31
The reversal of the inhibition on lipids synthesis by L-659,699 in arterial smooth muscle cells cultures; Carazo A et al.; The beta-lactone isolated from Fusarium sp . termed L-659,699 is a potent specific inhibitor of the enzyme 3-hydroxi-3-methylglutaril coenzyme A (HMG-CoA) synthase . In cultures of smooth muscle cells (SMC) isolated from aortic-arch of control (C-SMC) and 5% of cholesterol diet (Ch-SMC) treated chicks, the incorporation of (14C)-acetate to lipids (cholesterol, triacylglycerides and cholesterol ester) were greater in Ch-SMC cultures than in C-SMC and the presence of 0.05 microM L-659,699 for 2 h in the incubation medium decrease the synthesis of cholesterol however the triacylglycerides synthesis increase . The effect of inhibitor is stronger in young cultures (3-4 steps) than in the older ones (11-12 steps) . In young C-SMC and Ch-SMC cultures the inhibition of cholesterol and triacylglycerides synthesis by L-659,699 was reversal.

Cancer, 2001 Aug 1, 92(3), 601 - 8
Randomized phase II study of cyclophosphamide, doxorubicin, and vincristine compared with single-agent carboplatin in patients with poor prognosis small cell lung carcinoma; White SC et al.; BACKGROUND: Information on the effect of chemotherapy in a group of patients with poor prognosis, poor performance status small cell lung carcinoma (SCLC) is scarce . A randomized study comparing single-agent carboplatin with combination chemotherapy in this largely unreported population of SCLC patients was undertaken . METHODS: One hundred nineteen patients were allocated to four cycles of either cyclophosphamide, doxorubicin, and vincristine (CAV) or single-agent carboplatin . Patients had either a Karnofsky performance score < or = 50 and/or a prognostic score indicative of a 1-year survival rate < or = 15% . RESULTS: Grade 3-4 neutropenia and intravenous antibiotic use were significantly more common with the CAV regimen (P < 0.005) . Conversely, Grade 3-4 thrombocytopenia was more common (P < 0.0009) and platelet transfusion was more frequent (P < 0.05) with carboplatin therapy . Nonhematologic toxicity was similar in both treatment arms, except for alopecia with CAV therapy (P < 0.0007) . Symptom relief occurred in 48% and 41% of patients in the CAV and carboplatin treatment arms, respectively . Dyspnea was improved in 66% and 41% of patients and cough was improved in 21% and 7% of patients in the CAV and carboplatin treatment arms, respectively . CAV therapy produced a higher response rate than carboplatin (38% vs . 25%), but this was not statistically significant (P = 0.15) . The median overall survival for patients in the CAV and carboplatin treatment arms was 17 weeks and 15.9 weeks, respectively, with 1-year survival rates of 12% and 6% . CONCLUSIONS: Single-agent carboplatin is a feasible treatment in patients with poor prognosis SCLC and produces response rates, relief of tumor-related symptoms, and survival similar to what is seen in patients who receive CAV chemotherapy . The lower risk of life-threatening sepsis and less need for hospitalization or intravenous antibiotic courses is advantageous in this susceptible patient population .

Nucleic Acids Res, 2001 Aug 15, 29(16), 3413 - 23
Solution structure of an oligonucleotide containing an abasic site: evidence for an unusual deoxyribose conformation; Hoehn ST et al.; The antitumor antibiotic bleomycin causes two major lesions in the deoxyribose backbone of DNA: formation of 4'-keto abasic sites and formation of strand breaks with 3'-phosphoglycolate and 5'-phosphate ends . As a model for the 4'-keto abasic site, we have characterized an abasic site (X) in d(CCAAAGXACTGGG).d(CCCAGTACTTTGG) by two-dimensional NMR spectroscopy . A total of 475 NOEs and 101 dihedral angles provided the restraints for molecular modeling . Four unusual NOEs were observed between each anomer of the abasic site and the neighboring bases . In addition, four coupling constants for adjacent protons of the deoxyribose of both the alpha and beta anomers of the abasic site were observed . The modeling suggests that for both anomers the abasic site is extrahelical, without significant distortion of the backbone opposite the lesion . The coupling constants further allowed assignment of an unusual sugar pucker for each anomer . The unique position of the abasic site in our structural model for each anomer is discussed in terms of repair of such lesions in vivo.

Transplantation, 2001 Aug 15, 72(3), 463 - 76
Studies of Pediatric Liver Transplantation (SPLIT): year 2000 outcomes; SPLIT Research Group; BACKGROUND: Initiated in 1995, the Studies of Pediatric Liver Transplantation (SPLIT) registry database is a cooperative research network of pediatric transplantation centers in the United States and Canada . The primary objectives are to characterize and follow trends in transplant indications, transplantation techniques, and outcomes (e.g., patient/graft survival, rejection, growth parameters, and immunosuppressive therapy.) METHODS: As of June 15, 2000, 29 centers registered 1144 patients, 640 of whom received their first liver-only transplant while registered in SPLIT . Patients are followed every 6 months for 2 years and yearly thereafter . Data are submitted to a central coordinating center . RESULTS: One/two-year patient survival and graft loss estimates are 0.85/0.82 and 0.77/0.72, respectively . Risk factors for death include: in ICU at transplant (relative risk (RR)=2.63, P<0.05) and height/weight deficits of two or more standard deviations (RR=1.67, P<0.05) . Risk factors for graft loss include: in ICU at transplant (RR=1.77, P<0.05) and receiving a cadaveric split organ compared with a whole organ (RR=2.3, P<0.05) . The percentage of patients diagnosed with hepatic a . and portal v . thrombosis were 9.7% and 7%, respectively; 15% had biliary complications within 30 days . At least one re-operation was required in 45% . One/two-year rejection probability estimates are 0.60/0.66 . Tacrolimus, as primary therapy posttransplant, reduces first rejection risk (RR=0.70, P<0.05) . Eighty-nine percent of school-aged children are in school full-time, 18 months posttransplant . CONCLUSIONS: This report provides one of the first descriptions of characteristics and clinical courses of a multicenter pediatric transplant population . Observations are subject to patient selection biases but are useful for generating hypothesis for future studies.

Chest, 2001 Aug, 120(2), 508 - 13
Pulmonary complications in cardiac transplant recipients; Lenner R et al.; BACKGROUND: The incidence of pulmonary complications in heart transplant recipients has not been extensively studied . We report pulmonary complications in 159 consecutive adult orthotopic heart transplantations (OHTs) performed in 157 patients . Materials and methods: Retrospective review of medical records . RESULTS: Forty-seven of 159 recipients (29.9%) had 81 pulmonary complications . Pneumonia was the most common (n = 27), followed by bronchitis (n = 15), pleural effusion (n = 10), pneumothorax (n = 7), prolonged respiratory failure requiring tracheotomy (n = 7), and obstructive sleep apnea syndrome (n = 6) . All patients with late-onset (> 6 months after transplantation) community-acquired bacterial pneumonia presented with fever, cough, and a new lobar consolidation on the chest radiograph, and responded promptly to empiric antibiotics without undergoing an invasive diagnostic procedure . In contrast, early-onset nosocomial bacterial pneumonias carried a 33.3% mortality rate . A positive tuberculin skin test result was associated with a significantly higher rate of pulmonary complications (62.5% vs 26.8%, p = 0.007) . Lung cancer and posttransplant lymphoproliferative disorder (PTLD) developed exclusively in 6 of the 61 patients (8.1%) who received induction immunosuppression with murine monoclonal antibody (OKT3) . CONCLUSION: Pulmonary complications are common following heart transplantation, occurring in 29.9% of recipients, and are attributed to pneumonia of primarily bacterial origin in one half of cases . Late-onset community-acquired pneumonia carried an excellent prognosis following empiric antibiotic therapy, suggesting that in the appropriate clinical setting invasive diagnostic procedures are unnecessary . Analogous to reports in other solid-organ transplant recipients, induction therapy with OKT3 was associated with an increased incidence of lung cancer and PTLD . Overall, the development of pulmonary complications after OHT has prognostic significance given the higher mortality in this subset of patients.

Biochemistry, 2001 Aug 21, 40(33), 9950 - 6
Thermodynamic characterization of ligand-induced conformational changes in UDP-N-acetylglucosamine enolpyruvyl transferase; Samland AK et al.; The binding of UDP-N-acetylglucosamine (UDPNAG) to the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) was studied in the absence and presence of the antibiotic fosfomycin by isothermal titration calorimetry . Fosfomycin binds covalently to MurA in the presence of UDPNAG and also in its absence as demonstrated by MALDI mass spectrometry . The covalent attachment of fosfomycin affects the thermodynamic parameters of UDPNAG binding significantly: In the absence of fosfomycin the binding of UDPNAG is enthalpically driven (DeltaH = -35.5 kJ mol(-1) at 15 degrees C) and opposed by an unfavorable entropy change (DeltaS = -25 J mol(-1) K(-1)) . In the presence of covalently attached fosfomycin the binding of UDPNAG is entropically driven (DeltaS = 187 J mol(-1)K(-1) at 15 degrees C) and associated with unfavorable changes in enthalpy (DeltaH = 28.8 kJ mol(-1)) . Heat capacities for UDPNAG binding in the absence or presence of fosfomycin were -1.87 and -2.74 kJ mol(-1) K(-1), respectively, indicating that most ( approximately 70%) of the conformational changes take place upon formation of the UDPNAG-MurA binary complex . The major contribution to the heat capacity of ligand binding is thought to be due to changes in the solvent-accessible surface area . However, associated conformational changes, if any, also contribute to the experimentally measured magnitude of the heat capacity . The changes in solvent-accessible surface area were calculated from available 3D structures, yielding a DeltaC(p) of -1.3 kJ mol(-1) K(-1); i.e., the experimentally determined heat capacity exceeds the calculated one . This implies that other thermodynamic factors exert a large influence on the heat capacity of protein-ligand interactions.

Clin Orthop, 2001 Aug, (389), 185 - 90
Calcific myonecrosis of the leg: a case report and review of the literature; Wang JW et al.; Calcific myonecrosis is a rare complication of the leg after trauma . It usually develops as a late sequelae of compartment syndrome . Only approximately 21 cases have been reported in the English literature . The reported cases mostly have involved the anterior compartment of the leg . The current authors report the case of a 49-year-old man with a huge mass that involved the anterior and posterior compartments of the leg 30 years after initial trauma . Soft tissue sarcoma was suspected initially . A secondary infection developed after open incisional biopsy . After extensive debridement and closure of the wound over antibiotic-impregnated cement beads and a suction drain followed by compressive dressings, there has been no recurrence of the lesion or infection.

Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi, 1999 May, 15(3), 211 - 3
{Analysis of factors influencing healing time of burn wounds}; Chai J et al.; OBJECTIVE: To analyze the factors influencing healing time, length of hospital stay and hospital costs in burn patients . METHODS: Seven hundred and ninety-one burn patients with principal component analysis were studied retrospectively . RESULTS: There were some factors that influence healing time, including total area of burn, the area of full-thickness burn, the area of partial-thickness burn, inhalation injury, sepsis, shock, visceral complication, combined injuries, the size of surgical excision, the time of surgical excision, whether or not excision of burn wound was done in shock stage, and use of antibiotic, etc . Further analysis indicated that the patients undergo escharectomy during shock stage had better recovery with lower incidence of visceral complications and sepsis, especially in those with major burn over 30 percent TBSA . CONCLUSION: To reduce healing time of burn patients, there are many effective methods such as the prevention and treatment of shock, sepsis, visceral complication, and appropriate use of antibiotics . The most important factor to reduce healing time of burn patients is escharectomy as early as possible for major burns.

Orthopade, 2001 Mar, 30(3), 176 - 81
{Incidence and detection of nosocomial infections in technical orthopedics}; Homberg C et al.; The significance of nosocomial infections is increasing . The reasons for this are a higher concentration of problematic patients in hospitals due to the increasing number of outpatient surgeries, the increase of invasive therapeutic and diagnostic procedures, the growing share of immunodeficient patients as well as the increase in antibiotic-resistant and multiresistant pathogenic organisms . Basic changes in the medical system call for a systematic discussion about directed quality management . Surveillance, i.e., the systematic registration and evaluation of occurred diseases as well as the feedback to the personnel in charge is very important in this context, particularly when complemented by comprehensive hygienic measures . The growing significance of hospital infections increasingly triggered by multiresistant pathogenic organisms emphasizes the importance of general prevention . Each hospital has to determine which surveillance methods for the registration of nosocomial infections and multiresistant pathogenic organisms are the most appropriate under their respective conditions . To get a first idea of possible problem areas, prevalence studies are very suitable for the start before moving on to well-directed incidence studies in certain wards and for certain kinds of infection.

Saudi Med J, 2000 Jul, 21(7), 672 - 4
Tracheobronchial foreign bodies in children; Ben Amer JH et al.; OBJECTIVE: The objective of this study is to prove that rigid bronchoscopy is a relatively safe procedure in experts' hands and should be carried out in children whenever symptoms like persistent cough, chest infection or stridor persist despite proper antibiotic therapy . METHODS: A review of 534 bronchoscopies in children was carried out between August 1988 and May 1995 . Three hundred and fifteen were male and 219 were female children . The most common age was between 1 and 2 years while the mean age being 1 year 10 months . RESULTS: Out of 534 brochoscopies, 332 were positive for foreign bodies in the tracheosbronchial tree and 202 were negative . The most common site of lodgment of foreign body was the right bronchus . The clinical presentation was variable . An increase in the number of cases was observed . A variety of foreign bodies were encountered, the majority being peanuts . CONCLUSION: In our opinion rigid bronchoscopy is a relatively safe procedure and should be carried out in children whenever symptoms like persistent cough, chest infection or stridor persist despite proper antibiotic therapy.

Appl Microbiol Biotechnol, 2001 Jul, 56(1-2), 9 - 16
Pharmaceutically relevant metabolites from lichens; Muller K; Lichen metabolites exert a wide variety of biological actions including antibiotic, antimycobacterial, antiviral, antiinflammatory, analgesic, antipyretic, antiproliferative and cytotoxic effects . Even though these manifold activities of lichen metabolites have now been recognized, their therapeutic potential has not yet been fully explored and thus remains pharmaceutically unexploited . In this mini-review, particular attention is paid to the most common classes of small-molecule constituents of lichens, from both the chemical viewpoint and with regard to possible therapeutic implications . In particular, aliphatic acids, pulvinic acid derivatives, depsides and depsidones, dibenzofuans, anthraquinones, naphthoquinones as well as epidithiopiperazinediones are described . An improved access to these lichen substances in drug discovery high-throughput screening programs will provide impetus for identifying novel lead-compounds with therapeutic potential and poses new challenges for medicinal chemistry.

Mayo Clin Proc, 2001 Aug, 76(8), 794 - 8
Utility of endoscopic ultrasonography in endoscopic drainage of pancreatic pseudocysts in selected patients; Norton ID et al.; OBJECTIVES: To determine the effect of endoscopic ultrasonography (EUS) on endoscopic drainage of pancreatic pseudocysts and to determine patency with fistula dilation and placement of multiple stents . PATIENTS AND METHODS: Between September 1995 and January 1999, 19 patients underwent endoscopic drainage of pancreatic pseudocysts, 17 of whom were assessed by EUS before drainage . Radial EUS scanning was used to detect an optimal site of apposition of pseudocyst and gut wall, free of intervening vessels . A fistula was created with a fistulatome, followed by balloon dilation of the fistula tract . Patency was maintained with multiple double pigtail stents . The primary goal of this retrospective study was to determine whether EUS affected the practice of endoscopic drainage of pancreatic pseudocysts . RESULTS: In 3 patients, drainage was not attempted based on EUS findings . In the other 13 patients (14 pseudocysts), creation of a fistula was successful on 13 occasions, and no immediate complications occurred . However, 1 patient subsequently developed sepsis that required surgery . All other patients were treated with balloon dilation, multiple stents, and antibiotics, with no septic complications . Of 14 pseudocysts (in 13 patients), 13 (93%) resolved . CONCLUSIONS: Results of EUS may alter management of patients considered for endoscopic drainage of pancreatic pseudocysts . Endoscopic ultrasonography was useful for selecting an optimal and safe drainage site . The combination of balloon dilation, multiple stents, and antibiotics appears to resolve pancreatic pseudocysts without septic complications.

Monaldi Arch Chest Dis, 2001 Apr, 56(2), 132 - 6
Bacterial community-acquired pneumonia in children: changes in causative agents; Korppi M et al.; In this review, the authors present the current concept on the bacterial etiology of pediatric community-acquired pneumonia . The changes which have taken place after the introduction of modern serology for the diagnosis of bacterial pneumonia are discussed . Based on the current knowledge, the authors present the recommendations for empirical antibiotic therapy of pediatric community-acquired pneumonia in basically healthy children.

Bone Marrow Transplant, 2001 Jul, 28(1), 83 - 7
Successful unrelated bone marrow transplantation for a patient with chronic granulomatous disease and associated resistant pneumonitis and Aspergillus osteomyelitis; Watanabe C et al.; We describe the successful treatment of a 20-year-old patient with chronic granulomatous disease (CGD), by unrelated bone marrow transplantation (UBMT) . The patient is relatively old compared to other CGD patients treated with BMT . He had had repeated serious infections from early childhood and was diagnosed as CGD, gp91-phox deficiency . Prolonged antibiotic-resistant pneumonitis worsened when the patient was 18 years old . In addition, he suffered Aspergillus osteomyelitis and acute renal failure due to amphotericin B . He received 94 granulocyte transfusions from 94 adult donors and the infections gradually improved . In September 1998, at 20 years of age, he underwent UBMT from an HLA 6 antigen-matched male donor, with CY and TBI conditioning . He received MTX and CsA as prophylaxis against GVHD . No serious complications occurred and rapid engraftment was achieved . Acute GVHD (grade 2, at day 19) and chronic GVHD (limited, at day 192) occurred . However, both were easily controlled . The patient is alive and well with no late rejection 26 months after UBMT.

Rev Esp Quimioter, 2000 Dec, 13(4), 417 - 24
{Five-year analysis of extrahospital consumption of betalactams in Spain}; Calvo Plaza MI et al.; We carried out a qualitative and quantitative study to determine extrahospital consumption of both broad-spectrum penicillins and cephalosporins in Spain in the period 1993-1997 . Penicillins were the most consumed group, followed by macrolides and cephalosporins . Units and value (ptas.) of penicillins and cephalosporins during these five years show interannual variations . Nevertheless, monthly analysis of consumption for both groups showed a stable tendency, with peaks in winter months and drops in the summer . Both penicillins (54.38%) and cephalosporins (27.71%) were prescribed mainly for upper respiratory tract infections . Men received more penicillins and cephalosporins than women (51.02% and 55.09%) . Children under 11 years were the main group for consumption of both types of antibiotic, while patients aged 55-64 years were the group with the least consumption.

Biochem Soc Trans, 2001 Aug, 29(Pt 4), 565 - 70
Peptaibols: models for ion channels; Chugh JK et al.; Peptaibols are membrane-active polypeptides isolated from fungal sources . They are characterized by the presence of an unusual amino acid, alpha-aminoisobutyric acid, and a C-terminal hydroxylated amino acid . Peptaibols exhibit antibiotic activity against bacteria and fungi . Their amphipathic nature allows them to self-associate into oligomeric ion-channel assemblies which span the width of lipid bilayer membranes . Over 200 peptaibol sequences have been reported to date, which are compiled in the Peptaibol Database at Alignments of these sequences have been carried out in order to define a series of related subfamilies (SFs) with common sequence features thought to be important for channel formation . Crystal structures determined for a number of peptaibols from the various SFs provide the bases both for modelling of the channel structures and for modelling structures of other members of the same SFs.

Anticancer Res, 2001 May-Jun, 21(3B), 1665 - 71
PM-3, a benzo-gamma-pyran derivative isolated from propolis, inhibits growth of MCF-7 human breast cancer cells; Luo J et al.; Propolis has numerous biologic activities including antibiotic, antifungal, antiviral and anti-inflammatory properties . Several components isolated from propolis have been shown to have anticancer activity . This study demonstrates that the compound PM-3 (3-{2-dimethyl-8-(3-methyl-2-butenyl)benzopyran}-6-propenoic acid) isolated from Brazilian propolis markedly inhibits the growth of MCF-7 human breast cancer cells . This effect was associated with inhibition of cell cycle progression and induction of apoptosis . Treatment of MCF-7 cells with PM-3 arrested cells in the G1 phase and resulted in a decrease in the protein levels of cyclin D1 and cyclin E . PM-3 also inhibited the expression of cyclin D1 at the transcriptional level when examined in cyclin D1 promoter luciferase assays . Induction of apoptosis by PM-3 occurred within 48 hours after treatment of MCF-7 cells . The MCF-7 treated cells also displayed a decrease in the level of the estrogen receptor (ER) protein and inhibition of estrogen response element (ERE) promoter activity . Therefore, PM-3 merits further investigation with respect to breast cancer chemoprevention or therapy.

Ann Urol (Paris), 2001 Jul, 35(4), 229 - 33
{Perineoscrotal gangrene: report of 51 cases . Diagnostic and therapeutic features}; Tazi K et al.; OBJECTIVE: To approach the treatment of Fournier's gangrene . So, pathophysiology and etiology are recalled . METHODS: The authors present 51 cases of Fournier's gangrene treated from 1989 to 1998, their age ranged from 19 to 89 years . Data were collected on admission signs and symptoms, physical examination . Aggressive surgical debridement of all necrotic tissues was performed, Intravenous antibiotics and resuscitation fluid were also administered . RESULTS: All patients were male . In 20 cases (39%), there was no identifiable cause, and in 31 cases (61%), the etiology of gangrene was urethral (33%), anorectal (28%) and unknown (19%) . The average hospital stay was 30 days . Three cases underwent unilateral orchidectomy, six colostomy and in 17 cases, a suprapubic catheter was inserted . Mortality was high (18%) and essentially associated to debilated state and toxi-infectious context . CONCLUSION: Fournier's gangrene is a true urologic emergency potential lethal, which requires aggressive antibiotic and surgical treatment.

Zentralbl Neurochir, 2001 Feb, 62(1), 2 - 9
{Complications in the use of the halo fixator}; Schulze W et al.; 50 patients out of a total of 88 who underwent treatment using a halo-fixateur between 1987 and 1997 were available for a follow-up interview reviewing local complications and quality of life . Marginal discomfort was observed in 54% of patients, moderate complaints/transitory pain in 30%, prolonged and severe discomfort and pain in 16% . 62% of patients took no analgetics, 22% infrequently, and 16% continuously throughout treatment . In pin-tract infection local treatment was successful in 6 patients, in 3 patients the screws needed to be relocated . Complaints of dysphagia due to extended forced lordosis of the cervical spine could be corrected by adjusting the position of the halo ring in 3 out of 8 patients . 3 patients developed pressure sores which could be managed without surgical intervention . Proper fixation and placement of the pin-tracts are crucial in the application of the halo fixateur if complications are to be avoided . Superficial infections must be treated locally . If the infection persists immediate pin relocation and systemic antibiotic therapy have to be initiated.

JAMA, 2001 Aug 8, 286(6), 700 - 7
Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial; Merrer J et al.; CONTEXT: Whether venous catheterization at the femoral site is associated with an increased risk of complications compared with that at the subclavian site is debated . OBJECTIVE: To compare mechanical, infectious, and thrombotic complications of femoral and subclavian venous catheterization . DESIGN AND SETTING: Concealed, randomized controlled clinical trial conducted between December 1997 and July 2000 at 8 intensive care units (ICUs) in France . PATIENTS: Two hundred eighty-nine adult patients receiving a first central venous catheter . INTERVENTIONS: Patients were randomly assigned to undergo central venous catheterization at the femoral site (n = 145) or subclavian site (n = 144) . MAIN OUTCOME MEASURES: Rate and severity of mechanical, infectious, and thrombotic complications, compared by catheterization site in 289, 270, and 223 patients, respectively . RESULTS: Femoral catheterization was associated with a higher incidence rate of overall infectious complications (19.8% vs 4.5%; P<.001; incidence density of 20 vs 3.7 per 1000 catheter-days) and of major infectious complications (clinical sepsis with or without bloodstream infection, 4.4% vs 1.5%; P =.07; incidence density of 4.5 vs 1.2 per 1000 catheter-days), as well as of overall thrombotic complications (21.5% vs 1.9%; P<.001) and complete thrombosis of the vessel (6% vs 0%; P =.01); rates of overall and major mechanical complications were similar between the 2 groups (17.3% vs 18.8 %; P =.74 and 1.4% vs 2.8%; P =.44, respectively) . Risk factors for mechanical complications were duration of insertion (odds ratio {OR}, 1.05; 95% confidence interval {CI}, 1.03-1.08 per additional minute; P<.001); insertion in 2 of the centers (OR, 4.52; 95% CI, 1.81-11.23; P =.001); and insertion during the night (OR, 2.06; 95% CI, 1.04-4.08; P =.03) . The only factor associated with infectious complications was femoral catheterization (hazard ratio {HR}, 4.83; 95% CI, 1.96-11.93; P<.001); antibiotic administration via the catheter decreased risk of infectious complications (HR, 0.41; 95% CI, 0.18-0.93; P =.03) . Femoral catheterization was the only risk factor for thrombotic complications (OR, 14.42; 95% CI, 3.33-62.57; P<.001) . CONCLUSION: Femoral venous catheterization is associated with a greater risk of infectious and thrombotic complications than subclavian catheterization in ICU patients.

Ned Tijdschr Geneeskd, 2001 Jul 21, 145(29), 1377 - 80
{Delayed birth of the second child in multiple gestation}; Weemhoff M et al.; Five case histories illustrate the issue of delayed interval deliveries . In the first two cases, the first child was born at a gestational age of 20 and 18 weeks, respectively . The first woman (40 years old) gave birth to the second child after successful prolongation of pregnancy to a gestational age of 38 weeks . In the second case (28 years old), the attempt to delay delivery failed and the second child was born at 19 weeks of gestation . The third case (32 years old), illustrates the enormous differences in neonatal course between a child born at 26 weeks of gestation, who had to be treated at length for respiratory distress syndrome, hypotension and patent ductus arteriosus, and his twin brother born two weeks later and who recovered more quickly . The fourth case (24 years old) describes delayed delivery to allow administration of antenatal glucocorticoids . The last case (32 years old) deals with a serious maternal complication of placental abruption during an attempt to delay the birth of the second twin . Early tocolytic and antibiotic therapy may delay delivery and, in combination with antenatal glucocorticoids to stimulate lung maturation, may thereby improve the condition of the second twin . The role of cervical cerclage remains controversial . There is an important publication bias in the literature due to under-reporting of the failed attempts of delayed deliveries . In multiple gestation with imminent very preterm birth, delayed delivery of the second child is a feasible management option.

Microsurgery, 2001, 21(5), 202 - 7
Free tissue transfer in pregnancy: guidelines for perioperative management; Meger GR et al.; A successful free tissue transfer of serratus anterior muscle, to provide coverage for an open ankle defect in a pregnant patient, is described . Microvascular surgery in the presence of a viable pregnancy demands considerations unique to this situation . Although rarely possible, an attempt should be made to plan surgery to coincide with the second trimester, to lessen the risk of anesthesia to the fetus . Maternal positioning, fluid balance, and aspiration precautions need to be critically addressed . Close perioperative monitoring by an obstetrician is essential . The condition of pregnancy results in a hypercoagulable state that may lead to an increased risk of anastomotic failure . The use of anticoagulants results in increased risk of bleeding, not only for the patient but also for the fetus, as well as risk of teratogenic effects . Closely monitored heparin is considered safe in pregnancy as is low-molecular-weight dextran and low-dose aspirin . Additional considerations include the use of narcotics and sedatives for comfort postoperatively, as well as antibiotic choices, if indicated.

J Neurosci Res, 2001 Aug 1, 65(3), 208 - 19
Efficient gene transfer in mouse neural precursors with a bicistronic retroviral vector; Franceschini IA et al.; Gene transfer into neural precursors is a powerful approach to study the function of specific gene products during nervous system development . Here we describe a retrovirus-based methodology to transduce foreign genes into mouse neural precursors . We used a high-titer bicistronic retroviral vector that encodes a marker gene, placental alkaline phosphatase (plap), and a selection gene, neomycin phosphotransferase II (neoR), under the translational control of two retroviral internal ribosome entry segments . Transduction efficiency even without selection was up to 95% for multipotential neurospheres derived from embryonic striata and grown with basic fibroblast growth factor 2 . Expression of plap and neoR was sustained with time in culture and upon differentiation into neurons, astrocytes, and oligodendrocytes, as shown by double immunofluorescence labeling with cell type-specific markers, Western blotting, and neomycin resistance . However, levels of plap were decreased in differentiated oligodendrocytes . Transduction with the same vector of neonatal oligodendrocyte precursors grown in oligospheres consistently resulted in a lower proportion of plap-immunoreactive cells and enhanced cell death in the absence of neomycin . However, plap expression was maintained in some differentiated oligodendrocytes expressing galactocerebroside or myelin basic protein . In that neurospheres can be easily expanded in vitro and factors enabling their differentiation into the three main central nervous system cell types are being elucidated, this methodology could be used in the future to produce large number of transduced, differentiated neural cells .

QJM, 2001 Aug, 94(8), 423 - 8
Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis; Andres E et al.; Drug-induced agranulocytosis (DIA) is often caused by antithyroid drugs . We retrospectively studied the use of granulocyte colony-stimulating factor (G-CSF) therapy in antithyroid-DIA . Data for 20 patients (10 treated with G-CSF) with antithyroid-DIA (neutrophil count <0.5x10(9)/l) were extracted from a cohort study of DIA patients (n=110) . G-CSF (300 microg/day subcutaneously) was used where the neutrophil count was <0.1x10(9)/l, or the patient was aged >70 years, or there were severe features of infection or underlying disease . Mean patient age was 62 years (range 34-87); sex ratio (M/F) was 0.05 . Carbimazole (n=19) and benzylthiouracile (n=1) were the causative drugs, at mean doses of 30 mg/day (range 20-60) and 100 mg/day (range 50-150), respectively, for a mean of 37 days (range 31-90) . Antithyroid drugs were prescribed for Graves' disease (n=8), thyrotoxicosis related to amiodarone intake (n=6) and multinodular goitre (n=6) . Clinical features included isolated fever (n=7), pneumonia (n=5), septicaemia or septic shock (n=5) and acute tonsillitis (n=3) . Mean neutrophil count was 0.07+/-0.1x10(9)/l . No patient died . Mean durations of haematological recovery, antibiotic therapy and hospitalization were significantly reduced with G-CSF: 6.8+/-4 days vs . 11.6+/-5; 7.5+/-3.8 days vs . 12+/-4.5; and 7.3+/-4.8 days vs . 13+/-6.1, respectively (all p<0.05) . G-CSF induced flu-like symptoms in 30% of patients, but reduced overall costs.

Transpl Infect Dis, 2001 Sep, 3(3), 161 - 7
Aspergillosis in lung transplantation: incidence, risk factors, and prophylactic strategies; Gordon SM et al.; Invasive aspergillosis remains a significant cause of morbidity and mortality in transplantation, especially lung and allogeneic bone marrow transplant recipients . The epidemiology, classic and newly recognized risk factors, and incidence of aspergillosis are reviewed . Risk factors include environmental exposures, airway colonization, profound immunosuppression, neutropenia, prior cytomegalovirus infection, and renal dysfunction . Clinical and radiographic presentations of invasive aspergillosis are discussed, including some unusual manifestations in lung transplant recipients . Early and accurate diagnosis of aspergillosis remains a challenge, and diagnostic strategies are reviewed, with an emphasis on the chest computerized tomography scan and on transbronchial or open lung biopsy . Recent advances include prophylactic and pre-emptive antifungal strategies, newer therapeutic agents, and improved risk stratification.

Transpl Infect Dis, 2001 Sep, 3(3), 128 - 37
Infectious complications of lung transplantation; Alexander BD et al.; Lung transplantation is associated with a high incidence of infection which directly impacts the morbidity and mortality associated with the procedure . In addition, these infections may also have immunologic consequences that play a role in the evolution of lung injury syndromes, resulting in earlier loss of graft than otherwise would be expected to occur . Although bacteria are responsible for the majority of infections following lung transplantation, fungal infections are associated with the highest mortality . This paper is an overview of the major infectious complications encountered in the lung transplant population . The epidemiology, prophylaxis, and treatment of infections following lung transplantation are critical areas for continued research.

Stat Methods Med Res, 2001 Aug, 10(4), 251 - 65
A sensitivity analysis for publication bias in systematic reviews; Copas JB et al.; There is no simple method of correcting for publication bias in systematic reviews . We suggest a sensitivity analysis in which different patterns of selection bias can be tested against the fit to the funnel plot . Publication bias leads to lower values, and greater uncertainty, in treatment effect estimates . Two examples are discussed . An appendix lists the S-plus code needed for carrying out the analysis.

J Mol Biol, 2001 May 25, 309(1), 267 - 83
Solution structures of C-1027 apoprotein and its complex with the aromatized chromophore; Tanaka T et al.; C-1027 is one of the most potent antitumor antibiotic chromoproteins, and is a 1:1 complex of an enediyne chromophore having DNA-cleaving ability and a carrier apoprotein . The three-dimensional solution structures of the 110 residue (10.5 kDa) C-1027 apoprotein and its complex with the aromatized chromophore have been determined separately by homonuclear two-dimensional nuclear magnetic resonance methods . The apoprotein is mainly composed of three antiparallel beta-sheets: four-stranded beta-sheet (43-45, 52-54; 30-38; 92-94; 104-106), three-stranded beta-sheet (4-6; 17-22; 61-66), and two-stranded beta-sheet (70-72; 83-85) . The overall structure of the apoprotein is very similar to those of other chromoprotein apoproteins, such as neocarzinostatin and kedarcidin . A hydrophobic pocket with approximate dimensions of 14 A x 12 A x 8 A is formed by the four-stranded beta-sheet and the three loops (39-42; 75-79; 97-100) . The holoprotein (complex form with the aromatized chromophore) structure reveals that the aromatized chromophore is bound to the hydrophobic pocket found in the apoprotein . The benzodihydropentalene core of the chromophore is located in the center of the pocket and other substituents (beta-tyrosine, benzoxazine, and aminosugar moieties) are arranged around the core . Major binding interactions between the apoprotein and the chromophore are likely the hydrophobic contacts between the core of the chromophore and the hydrophobic side-chains of the pocket-forming residues, which is supplemented by salt bridges and/or hydrogen bonds . Based on the holoprotein structure, we propose possible mechanisms for the stabilization and the release of chromophore by the apoprotein.

J Endovasc Ther, 2001 Jun, 8(3), 262 - 7
Endovascular grafting of traumatic aortic aneurysms in contaminated fields; Kramer S et al.; PURPOSE: To evaluate the potential of endovascular stent-grafts to treat traumatic aortic lesions in contaminated areas . METHODS: Four patients (3 women; ages 26-78 years) underwent stent-grafting to repair an aortic rupture sustained in a motorcycle accident, aortic lacerations secondary to surgical treatment of spondylitis in 2 patients, and an aortobronchial fistula following surgical thoracic aortic repair 10 years earlier . Stent-grafts (2 Corvita, 1 Talent, and 1 Vanguard) were placed endoluminally into the infected areas via a transfemoral approach . Follow-up included erythrocyte sedimentation rate, white blood count, C-reactive protein, blood cultures, and computed tomography (CT) . RESULTS: The stent-grafts were successfully placed in all cases and excluded the aortic lesion . Under supportive antibiotic therapy, inflammation parameters returned to normal . CT imaging showed no evidence of paraprosthetic infection, nor were there any other complications over a follow-up that ranged from 3 to 34 months . CONCLUSIONS: Endovascular therapy may be an alternative in the acute management of aortic ruptures in the setting of infection . Long-term results are required for definitive evaluation of the method.

Hepatogastroenterology, 2001 Jul-Aug, 48(40), 1078 - 81
A 3-day anti-Helicobacter pylori therapy is a good alternative for bleeding peptic ulcer patients with Helicobacter pylori infection; Hsieh YH et al.; BACKGROUND/AIMS: One-week triple therapy has been recommended as a standard regimen for eradicating Helicobacter pylori infection . The emergence of antibiotic-resistant strains, adverse drug effects, poor compliance and high cost of therapy add problems to the management of these patients . In this study, we assessed whether a 3-day triple therapy could be effective in eradicating Helicobacter pylori infection in bleeding peptic ulcer patients . METHODOLOGY: Peptic ulcer patients with Helicobacter pylori infection were enrolled in this study . Patients enrolled at the outpatient department (group A) received a 7-day oral regimen: bismuth subcitrate colloid 300 mg + amoxicillin 500 mg + metronidazole 250 mg four times per day . Patients who were admitted to the wards due to peptic ulcer bleeding (group B) received a 3-day regimen including omeprazole 40 mg intravenously every 6 hours, amoxicillin 500 mg + metronidazole 250 mg orally four times daily after hemostasis had been achieved . Patients of both groups received omeprazole 20 mg once per day or cimetidine 400 mg twice daily per os for at least-one month after anti-Helicobacter pylori therapy . We followed every patient endoscopically two months after anti-Helicobacter pylori therapy . RESULTS: From June 1997 to April 1999, a total of 57 patients (30 in group A and 27 in group B) with gastric or duodenal ulcer and Helicobacter pylori infection completed anti-Helicobacter pylori therapy . Two months after anti-Helicobacter pylori therapy, peptic ulcer was found to be healed with a scar in 26 (86.7%) of group A and 23 (85.2%) of group B (P > 0.1) . The eradication rates of Helicobacter pylori in the two groups were not significantly different in an intention-to-treat analysis {group A: 78.8% (26/33), 95% CI: 64.9-92.7%; group B: 80% (24/30), 95% CI: 65.7-94.3%, P > 0.1} and in a per protocol analysis {group A: 86.7% (26/30), 95% CI: 74.5-98.9%, group B: 88.9% (24/27), 95% CI: 77.1-100.7%, P > 0.1} . Fewer side effects occurred in group B (3/30) than those in group A (7/33) (P > 0.1) . CONCLUSIONS: In patients with peptic ulcer bleeding a 3-day anti-Helicobacter pylori therapy is a good alternative for eradicating Helicobacter pylori infection.

Clin Cancer Res, 2001 Aug, 7(8), 2228 - 36
Modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule-dependent manner . See: E . A . Sausville, Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: sequence and tumor biology matters, Clin . Cancer Res., 7: 2155-2158, 2001; Munster PN et al.; 17-allyl-aminogeldanamycin (17-AAG) is an ansamycin antibiotic that binds to a highly conserved pocket in the Hsp90 chaperone protein and inhibits its function . Hsp90 is required for the refolding of proteins during cellular stress and the conformational maturation of certain signaling proteins . 17-AAG has antitumor activity in cell culture and animal xenograft models and is currently in clinical trial . It causes an RB-dependent G(1) arrest, differentiation, and apoptosis . RB-negative cells arrest in mitosis and undergo apoptosis . Hsp90 plays an important role in the cellular response to environmental stress . Therefore, we tested whether the regulation of Hsp90 function by 17-AAG could sensitize cells to cytotoxic agents . 17-AAG sensitized tumor cells to Taxol and doxorubicin . Taxanes cause growth arrest in mitosis and apoptosis . The addition of 17-AAG to cells after exposure to Taxol significantly increased both the activation of caspases 9 and 3 and apoptosis . In cells with intact RB, exposure to 17-AAG before Taxol resulted in G(1) arrest and abrogated apoptosis . Schedule dependence was not seen in cells with mutated RB, because both agents blocked cells in mitosis . Schedule- or RB-dependence was also not observed when cells were treated with 17-AAG and doxorubicin, a DNA-intercalating agent that acts on different phases of the cell cycle . These findings suggest that inhibition of Hsp90 function by 17-AAG enhances the apoptotic effects of cytotoxic agents . The sequence of drug administration and the RB status significantly influence efficacy.

J Control Release, 2001 Jul 6, 74(1-3), 203 - 11
Synthesis and characterization of HPMA copolymer-aminopropylgeldanamycin conjugates; Kasuya Y et al.; Geldanamycin (GDM) is a benzoquinone ansamycin antibiotic with anticancer activity . The use of drug delivery systems based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing lysosomally degradable oligopeptide (GFLG) spacers results in an increased therapeutic efficacy of anticancer drugs . The objective of this study was to synthesize HPMA copolymer-GDM conjugates with anticancer activity and reduced toxic side-effect of the compound . 17-(3-Aminopropylamino)-17-demethoxygeldanamycin (AP-GDM) was synthesized and converted into a polymerizable GDM derivative, N-methacryloylglycylphenylalanylglycyl-17-(3-aminopropylamino)-17-demethoxygeldanamycin {MA-GFLG-(AP-GDM)} . The structures of AP-GDM and MA-GFLG-(AP-GDM) were validated by mass spectroscopy, elemental analysis, and two-dimensional nuclear magnetic resonance . MA-GFLG-(AP-GDM) was copolymerized with HPMA and N-methacryloyglycylglycine p-nitrophenylester by radical precipitation polymerization . Water-soluble HPMA copolymer-AP-GDM conjugates (M(r)=16 kDa) were obtained . Monoclonal antibody OV-TL16, which recognizes the OA-3 antigen expressed on the OVCAR-3 human ovarian carcinoma cell line, was optionally attached to the HPMA copolymer-AP-GDM conjugate . Cytotoxicity of polymer-bound AP-GDM (both targeted and non-targeted) was determined using OVCAR-3 and another human ovarian carcinoma cell line, A2780 . The HPMA copolymer-AP-GDM conjugate was cytotoxic toward A2780 cells . Attachment of OV-TL16 antibody enhanced cytotoxicity of the conjugate toward OVCAR-3 cells.

Auris Nasus Larynx, 2001 Aug, 28(3), 257 - 9
Barotraumatic blowout fracture of the orbit; Suzuki H et al.; We report a rare case of a barotraumatic blowout fracture of the orbit . A 32-year-old woman presented with sudden swelling of the right orbital region after vigorous nose blowing . Computed tomography scan revealed a blowout fracture of the medial wall of the right orbit with orbital emphysema and herniation of the orbital soft tissue . She was treated with prednisolone and an antibiotic, and did not show diplopia or visual disturbance . Three different theories have so far been proposed to explain the mechanism of blowout fractures, globe-to-wall contact theory, hydraulic theory, and bone conduction theory . The present case indicates that blowout fractures of the orbit can be induced solely by a sudden change of pressure, thereby suggesting the validity of the hydraulic theory.

Rev Esp Enferm Dig, 2001 Jan, 93(1), 21 - 8
Decision-making process in long term acute cholecystitis; Cordoba Diaz de Laspra E et al.; OBJECTIVE: To demonstrate that the categorization of different therapeutic options is essential for the decision-making applied to clinical management . METHOD: This paper compares the usefulness of percutaneous echo-guided cholecystostomy as the first therapeutic option in acute long-term cholecystitis versus the exclusive surgical or clinical management . RESULT: We have analyzed the usefulness of different therapeutic options in a case of long term acute cholecystitis and we have obtained the following results: isolated intravenous antibiotic therapy (0.76), surgery (0.73) and echo-guided cholecystostomy (0.93) . This last option has provided good clinical-radiological results . CONCLUSION: Decision trees are a good methodological option as support of surgical and non surgical therapeutic procedures.

J Endod, 2001 Jan, 27(1), 53 - 6
Effect of prophylactic amoxicillin on endodontic flare-up in asymptomatic, necrotic teeth; Pickenpaugh L et al.; The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of prophylactic amoxicillin on the occurrence of endodontic flare-up in asymptomatic, necrotic teeth . Seventy patients participated and had a clinical diagnosis of an asymptomatic, necrotic tooth with associated periapical radiolucency . One hour before endodontic treatment, patients randomly received either 3 g of amoxicillin or 3 g of a placebo control in a double-blind manner . After endodontic treatment, each patient received: ibuprofen; acetaminophen with codeine (30 mg); and a 5 1/2-day diary to record pain, swelling, percussion pain, and number and type of pain medication taken . The results demonstrated 10% of the 70 patients had a flare-up characterized by moderate-to-severe postoperative pain or swelling that began approximately 30 h after endodontic treatment and persisted for an average of 74 h . Of the seven patients who had flare-ups, 4 were in the amoxicillin group and 3 were not . Prophylactic amoxicillin did not significantly (p = 0.80) influence the endodontic flare-up . We concluded that a prophylactic dose of amoxicillin before endodontic treatment of asymptomatic, necrotic teeth had no effect on the endodontic flare-up.

Acta Orthop Belg, 2001 Jun, 67(3), 300 - 3
Pneumoencephalomeningitis secondary to infected lumbar arthrodesis with a fistula: a case report; Guerado E et al.; Pneumocephalus associated with spinal problems is very rare . Association with encephalomeningitis secondary to a fistula after an infected elective lumbar spine fusion has not been previously reported . The authors report a case in which the clinical onset of pneumoencephalomeningitis occurred after an airplane flight . CT-scan and lumbar puncture were used to make diagnosis; the treatment was based on parenteral antibiotics . The symptoms and signs of infection and neurological deficit resolved but the fistula remained . Diagnosis in such cases must be based upon CT-scan and lumbar puncture . Treatment should consist of systemic antibiotic therapy . Surgical management of infection and fistula is desirable, should the status of the patient allow such a treatment . In any case, as airplane flights in such cases may predispose to pneumocephalus, patients with an infected CSF fistula should avoid airplane flights until the problem is solved.

Z Kardiol, 2001 Jun, 90(6), 385 - 93
{Current status of endocarditis prevention}; Jeserich M et al.; There are currently no randomized and carefully controlled human trials to definitively prove that endocarditis prophylaxis is efficient . Furthermore, most cases of endocarditis are not attributable to a medical procedure . Thus, even with a high level of application of endocarditis prophylaxis only a minority of cases could be prevented . Endocarditis is a rare disease . On the other hand, its morbidity is increasing! In addition, infective endocarditis remains still a major medical concern because of its mortality between 5% and 76% . In addition, in up to 40% of all patients suffering from endocarditis one or more heart valves have to be replaced in the following 5 to 8 years . Without treatment endocarditis has a lethality of 100% . Therefore, there is worldwide agreement that endocarditis prophylaxis is necessary . Combining the recommendations of the German and the American Heart Association, as well as the results of the European consensus conferences, with newer insights into the pathophysiology of endocarditis the following aspects are elucidated: depending on their risk of endocarditis patients are allocated into 3 groups . In the first group there are patients with prosthetic cardiac valves, patients who suffered from previous endocarditis and patients with complex cyanotic congenital heart disease and surgically constructed shunts or conduits of the aorta and/or pulmonary circulation . In these high-risk patients the prophylactic regimen for dental, oral, respiratory tract procedures is oral amoxycillin . In genitourinary and gastrointestinal procedures ampicillin and gentamicin i.v . is recommended . In patients with mostly congenital cardiac malformations, acquired valvular dysfunction, hypertrophic obstructive cardiomyopathy and mitral valve prolapse or thickened leaflets and valvular regurgitation oral amoxycillin is recommended for all medical procedures (second group) . The third group consists of patients with isolated secundum atrial defect, previous coronary bypass graft surgery, patients with cardiac pacemakers or defibrillators . In this patient cohort the individual risk of endocarditis is not higher than in the general population . Therefore, endocardits prophylaxis is not recommended.

J Mol Med, 2001 Jun, 79(5-6), 275 - 82
Expression of human beta-defensin-1 promotes differentiation of keratinocytes; Frye M et al.; Epithelial cells have been shown to express the antibiotic peptides human beta-defensins-1 and 2 . While beta-defensin-2 is known to be up-regulated by bacterial factors and proinflammatory mediators, the expression of beta-defensin-1 does not appear to be affected by these mediators . To determine the regulation and function of beta-defensin-1 we analyzed its expression upon stimulation of inflammatory mediators in vitro and ex vivo . In immortalized human cell lines (HaCaT) and nasal polyps beta-defensin-1 was not induced upon incubation with bacteria or proinflammatory mediators, suggesting that the inertness of beta-defensin-1 expression levels is not the result of the shortcoming of HaCaT cells . As proliferation and regeneration play an important role at sites of inflammation, we examined the expression level of beta-defensin-1 in relation to the differentiation and proliferation of HaCaT cells . beta-defensin-1 mRNA levels remained low during proliferation but were highly induced upon differentiation . In contrast, beta-defensin-2 expression was unaffected under these conditions . To examine the function of beta-defensin-1 in cellular proliferation and differentiation processes beta-defensin-1 was overexpressed in keratinocytes . Protein expression analysis of the differentiation marker keratin 10 revealed that its expression is highly induced in the presence of increased concentrations of beta-defensin-1 . Hence our data indicate that high expression of beta-defensin-1 promotes cell differentiation processes of keratinocytes.

J Pineal Res, 2001 Aug, 31(1), 23 - 30
Protective effect of melatonin against adriamycin toxicity in the rat; Agapito MT et al.; Adriamycin, an anthracyclinic antibiotic frequently used in quimioterapeutic treatments is highly toxic; it inhibits protein synthesis and provokes prooxidant effects . Melatonin has recently been shown to have high antioxidative properties . We tested if melatonin is able to neutralize the oxidative damage induced by a single dose (20 mg/kg, i.p.) of adriamycin preceded (3 days) and followed (7 days) by a low pharmacological dose (50 microg/kg, i.p.) of melatonin . After the administration of a single dose of adriamycin (20 mg/kg i.p.) to male Wistar rats, the reduced to oxidized glutathione (GSH/GSSG) ratio and the glutathione peroxidase (GPx, E.C . 1.11.1.9.) activity in the brain, intestine, heart, kidney, and lung were significantly reduced . When the treatment of adriamycin was preceded and followed by low pharmacological doses of melatonin, the decrease in the GSH/GSSG ratio was significantly reduced but the reduction in GPx activity was not attenuated . A significant increase in lipid peroxidation products was observed in brain, heart, and kidney tissues after a single administration of adriamycin, which was attenuated by pre- and post-treatment with a low pharmacological dose of melatonin . Our results demonstrate that oxidative damage induced by the antitumor drug, adriamycin, can be reduced by low pharmacological doses of melatonin.

J Exp Clin Cancer Res, 2001 Jun, 20(2), 165 - 73
Cost of de novo acute myeloid leukemia induction therapy in adults: analysis of EORTC-GIMEMA AML10 and FLANG regimens; Clavio M et al.; Since the social and financial impact of AML therapy is becoming more and more relevant we analyzed the cost of induction therapy of two different regimens . The first one is part of the widely employed EORTC-GIMEMA AML-10 and consists often days of therapy . The second (FLANG) is a short (three day), Fludarabine, Ara-C, mitoxantrone and G-CSF containing regimen . We first retrospectively analyzed the outcome of 77 consecutive AML patients with comparable clinical and haematological features receiving FLANG (25) or AML-10 (52), between June 1993 and October 1999, and observed equivalent CR rate, as well as DFS and overall survival duration . We then selected 9 non pretreated patients per group who reached CR after one course of therapy . Patients treated with FLANG had a statistically significant earlier platelet recovery compared to those treated with AML-10, fewer days of intravenous antibiotic therapy (14/22, respectively, p < 0.05), and a shorter hospitalization period (22/33 days, p < 0.01) . FLANG was significantly more expensive than AML 10 as far as the cost of antiblastic drugs (p < 0.01) and G-CSF support (p < 0.05) are concerned . On the contrary, the expense for antiemetic drugs (p < 0.01) and the cost of personnel and other services ($5,906/$3,970, p < 0.05) were higher for AML-10 than for FLANG . Overall, the average costs of FLANG and AML10 were $9,269 and $12,424 respectively (p < 0.05; difference = -25%) . Our study seems to indicate that, compared to AML-10, FLANG induction is as effective, less expensive and it allows for a decrease in the length of hospitalization and thus for better exploitation of the financial resources of Hematology-Oncology departments.

Pediatrics, 2001 Aug, 108(2), 477 - 81
Optic neuropathy in children with Lyme disease; Rothermel H et al.; Involvement of the optic nerve, either because of inflammation or increased intracranial pressure, is a rare manifestation of Lyme disease . Of the 4 children reported here with optic nerve abnormalities, 2 had decreased vision months after disease onset attributable to optic neuritis, and 1 had headache and diplopia early in the infection because of increased intracranial pressure associated with Lyme meningitis . In these 3 children, optic nerve involvement responded well to intravenous ceftriaxone therapy . The fourth child had headache and visual loss attributable to increased intracranial pressure and perhaps also to optic neuritis . Despite treatment with ceftriaxone and steroids, he had persistent increased intracranial pressure leading to permanent bilateral blindness . Clinicians should be aware that neuro-ophthalmologic involvement of Lyme disease may have significant consequences . If increased intracranial pressure persists despite antibiotic therapy, measures must be taken quickly to reduce the pressure.

Prim Care, 2001 Sep, 28(3), 607 - 28, vii
Acute and chronic pancreatitis; Vlodov J et al.; Acute pancreatitis has multiple causes, an unpredictable course, and myriad complications . The diagnosis relies on a combination of history, physical examination, serologic markers, and radiologic findings . The mainstay of therapy includes aggressive hydration, maintenance of NPO, and adequate analgesia with narcotics . Antibiotic and nutritional support with total parenteral nutrition should be used when appropriate.

Gene, 2001 Jul 25, 273(1), 97 - 104
The TGV transgenic vectors for single-copy gene expression from the Escherichia coli chromosome; Gumbiner-Russo LM et al.; Plasmid-based cloning and expression of genes in Escherichia coli can have several problems: plasmid destabilization; toxicity of gene products; inability to achieve complete repression of gene expression; non-physiological overexpression of the cloned gene; titration of regulatory proteins; and the requirement for antibiotic selection . We describe a simple system for cloning and expression of genes in single copy in the E . coli chromosome, using a non-antibiotic selection for transgene insertion . The transgene is inserted into a vector containing homology to the chromosomal region flanking the attachment site for phage lambda . This vector is then linearized and introduced into a recombination-proficient E . coli strain carrying a temperature-sensitive lambda prophage . Selection for replacement of the prophage with the transgene is performed at high temperature . Once in the chromosome, transgenes can be moved into other lysogenic E . coli strains using standard phage-mediated transduction techniques, selecting against a resident prophage . Additional vector constructs provide an arabinose-inducible promoter (P(BAD)), P(BAD) plus a translation-initiation sequence, and optional chloramphenicol-, tetracycline-, or kanamycin-resistance cassettes . These Transgenic E . coli Vectors (TGV) allow drug-free, single-copy expression of genes from the E . coli chromosome, and are useful for genetic studies of gene function.

Vaccine, 2001 Aug 14, 19(31), 4373 - 7
Live attenuated influenza virus vaccines: new options for the prevention of influenza; Nichol KL; Live attenuated influenza virus (LAIV) vaccines present new possibilities for the prevention and control of influenza . Administered intranasally, LAIV vaccines offer a needle-free route of administration . These investigational vaccines have also been shown to be safe and effective in children and healthy working adults . A 2-year placebo-controlled trial among young children (1996-1997 and 1997-1998 influenza seasons) demonstrated that LAIV vaccine was associated with a 92% reduction in laboratory-confirmed cases of influenza . Vaccination also significantly reduced episodes of otitis media and antibiotic use . In a placebo-controlled trial among healthy working adults during the 1997-1998 season, LAIV vaccine significantly reduced episodes of febrile upper respiratory tract illness and illness-associated work loss, health-care use, and antibiotic use . Seventy percent of study participants self-administered the vaccine . An economic analysis of the benefits of LAIV vaccine in this population suggests that the break-even cost for LAIV vaccine and its administration for healthy working adults would be about $39 . For both children and healthy adults, LAIV vaccine provided substantial protection during the 1997-1998 season when the predominant circulating virus, the A/Sydney variant, was not contained in the vaccine . Studies are still underway to evaluate the potential incremental benefits of LAIV vaccine in addition to inactivated vaccine in high-risk populations . LAIV vaccines will be an important addition to the armamentarium for fighting influenza.

Rev Esp Enferm Dig, 2001 Jun, 93(6), 372 - 89
Helicobacter pylori eradication versus one-year maintenance therapy: effect on relapse and gastritis outcome; Mones J et al.; OBJECTIVE: The aim of this study was to determine ulcer healing and H . pylori eradication rates obtained with triple therapy (omeprazole, amoxicillin and clarithromycin) . Ulcer relapsing rate one year after eradication was also assessed . Maintenance therapy with placebo was compared with ranitidine therapy and the effect of eradication on histological variables of the gastric mucosa was studied . METHODS: A prospective, double-blind parallel study was performed in 85 patients endoscopically diagnosed of duodenal ulcer H . pylori positive . Patients were randomized to a 7-days triple therapy (group A) or omeprazole plus antibiotic placebo (group B) . All patients were treated only with omeprazole for the next three weeks . Patients with ulcer healing after treatment were entered in a one-year follow up phase with ranitidine placebo (group A) or ranitidine (group B) . Endoscopy and biopsies were performed at baseline, after treatment (5 weeks) and after 12 months of follow-up or when relapsing symptoms appeared . RESULTS: Healing rate was 90.2% in group A and 85.7% in group B . Eradication rate was 78% in group A and 0% in group B . Out of 37 healed patients in group A, eradication was achieved in 29 and only one relapse was found (3.4%) . Three out of eight patients with healing but without eradication relapsed at 12 months (35%) (p < 0.05) . Histopathological results showed statistically significant differences (p < 0.05) between eradicated and non eradicated patients in terms of severity of inflammation and intestinal metaplasia, but not in terms of atrophy . CONCLUSIONS: H . pylori eradication is useful to prevent ulcer relapse and to improve gastric mucosa status.

Cir Pediatr, 2001 Apr, 14(2), 73 - 5
{Laparoscopic splenectomy in pediatric hematologic diseases}; Martinez Ibanez V et al.; INTRODUCTION: Surgical acceptance of the laparoscopic splenectomy in the pediatric hematological disorders has improved due to safety, to relif postoperative pain, and to reduce the hospital stay . The aim of this study is present our surgical laparoscopic technique performed . MATERIAL AND METHODS: Eight patients, 6 spherocytosis (age ranged: 6-14 years, average age: 9.5 years; 5 girls and 1 boy) and 2 cases of autoimmune hemolytic anemia (both boys of 18 months and 4 years) underwent laparoscopic splenectomy . The Trias-Targarona technique has been performed placing the patient at the right lateral-decubitus position . Four trocars are placed, two of 5 mm in the posterior axillary line and epigastrium and other 2 trocars of 12 mm, in the middle of them . RESULTS: In all these 8 patients a laparoscopic splenectomy was completely performed . We had 2 cases with problems with the sac introduction . Cosmetic results have been excellent and we changed the 7-day antibiotic protocol for 2-day protocol . The surgical time has changed from 3 to 2 hours . CONCLUSIONS: With laparoscopic splenectomy we can give an adequate response to hematological disorders in children with a acceptable surgical time, an excellent cosmetic result with a minimum postoperative time and a very short hospital stay.

Hua Xi Kou Qiang Yi Xue Za Zhi, 1997 Feb, 15(1), 28 - 30, 54
{A study of therapeutic efficacy of Koukangning gargle in the treatment of oral mucositis}; Zeng G et al.; A study of therapeutic efficacy was carried out in 118 patients with oral mucositis (recurrent oral aphthous ulceration, erosive lichen planus, herptic stomatitis and infectious oral mucosal hematoma) at random . As a topical medication, Koukangning gargle was applied to 59 patients of the experimental group, 29 patients of the control group 1 applied Dobell's solution to rinse their mouths, and 30 patients of the control group 2 applied Koutai solution . A satisfactory result was observed in the experimental group, its effectiveness and effective rates rose more than those of control group 1 at both treatments for 3 days and 6 days . Between the two groups, there were markedly significant difference (P < 0.005, P < 0.01, P < 0.005, P < 0.005) . Koukangning gargle was nontoxic and no side-effects in the clinical tests . Its efficacy was no significant difference compared with the control group 2 . Experimental study demonstrates that it possesses anti-inflamation effect and excellent antibiotic effect, therefore it is a new gargle for rinse mouth combined traditional Chinese medicine with Western medicine.

J Pediatr Surg, 2001 Aug, 36(8), 1302 - 3
The utility of lung biopsy in recipients of stem cell transplantation; Dunn JC et al.; BACKGROUND/PURPOSE: Pulmonary infiltrates in recipients of stem cell transplantation often present as diagnostic dilemmas . Although lung biopsy may establish the diagnosis of parenchymal disease, it remains unclear whether such a procedure results in a significant change in the patient's treatment and outcome . This study evaluates the efficacy of lung biopsy in recipients of stem cell transplantation . METHODS: The medical records of 15 stem cell transplant recipients who underwent 18 lung biopsies were reviewed . The indications for stem cell transplantation were leukemia in 10 patients, lymphoma in 2, histiocytosis in 1, neuroblastoma in 1, and Ewing's sarcoma in 1 . The results of the lung biopsies were correlated to the clinical management and outcomes . RESULTS: The overall mortality rate was 67% (10 patients) . Eight of the 9 patients who required mechanical ventilatory support at the time of lung biopsy died . The pathologic diagnoses were pneumonitis in 6 biopsies, fibrosis in 6, brochiolitis obliterans organizing pneumonia in 3, hemorrhage in 2, and infarction in 1 . Therapy was changed in 1 patient who improved after a course of steroids for bronchiolitis obliterans organizing pneumonia . Lung biopsy cultures were positive in 6 patients but rarely resulted in changes in antibiotic therapy . CONCLUSIONS: Results of very few lung biopsies performed in stem cell transplant recipients redirected therapy . Furthermore, the ultimate outcome of these patients were not improved by the results of lung biopsies .

Saudi Med J, 2001 Jul, 22(7), 610 - 5
Brucellosis in children of Dhofar Region, Oman; El-Amin EO et al.; OBJECTIVE: To study the epidemiological and clinical pattern of brucellosis in children of Dhofar and to ascertain the efficacy of a pre-determined antibiotic regimen to treat the disease . METHODS: The study was hospital based and was carried out prospectively for 3 years . All cases diagnosed to have brucellosis on clinical and serological basis were entered into the study . The epidemiological background and clinical presentations were analyzed and the clinical response to a combination of oral rifampicin and co-trimoxazole was evaluated . RESULTS: Three hundred and seventy five cases of brucellosis were eligible for the study . Ingestion of raw milk and its products were responsible for causation of the disease in 63% of cases . Eighty three per cent had direct contact with animals mainly cattle . A minority of 4.5% denied ingestion of raw milk or coming into direct contact with animals . Fever was the most common presenting feature at 91% . We identified 2 distinct groups of presentation: Seventy per cent of those who presented with arthritis belonged to the older age group (7.34 years, standard deviation 2.64) . They did not have a systemic illness . The younger age group presented with severe systemic illness associated with severe leucopenia and thrombocytopenia . The clinical response to the combination of rifampicin and co-trimoxazole was satisfactory in 90% of patients and 98% of brucella species isolated from the blood of patients were sensitive to both antibiotics used . CONCLUSION: Ingestion of infected milk and contact with infected animals are the main causes of human brucellosis, although aerial transmission from contaminated environmental soil could not be excluded . The main clinical presentation of brucellosis in children is fever but the skeletal manifestations of the disease are significant . The hematological manifestations of the disease in endemic areas deserve special attention . The combination of oral rifampicin and co-trimoxazole for 6 weeks is adequate to treat most cases of brucellosis in children.

J Exp Bot, 2001 Aug, 52(361), 1697 - 702
Transformation of Lotus japonicus using the herbicide resistance bar gene as a selectable marker; Lohar DP et al.; Transgenic plants of the model legume Lotus japonicus were regenerated by hypocotyl transformation using a bar gene as a selectable marker . The bar encodes for Phosphinothricin Acetyl Transferase that detoxifies phosphinothricin (PPT), the active ingredient of herbicides such as Ignite (AgrEvo) and Basta (Hoechst) . Transgenic L . japonicus plants resistant to PPT were positive upon PCR by bar gene-specific primers . In 5 out of 7 independent lines tested, PPT resistance segregated as a single dominant allele indicating a single T-DNA insertion into the plant genome . All regenerated plants were fertile and void of visible somaclonal abnormalities contrary to 14% infertility when antibiotic selectable markers were used . The lack of somaclonal variation, ease of PPT application and low cost of PPT makes this protocol an attractive alternative for the regeneration of transgenic L . japonicus . The production of PPT herbicide-resistant L . japonicus plants may have significant commercial applications in crop production.

Intern Med J, 2001 Apr, 31(3), 181 - 3
Is there another chapter in the Helicobacter pylori/peptic ulcer disease story?
Clancy RL, Pang G.
The role of Helicobacter pylori in the production of mucosal damage has largely been considered within a simple infection paradigm, because to date eradication has appeared to be a predictable outcome of antibiotic therapy . Changes in the epidemiology and management of peptic ulcer disease, however, require a more comprehensive framework to understand these shifting clinical patterns . The present review examines mucosal damage as an outcome of a complicated host-parasite relationship, with alterations in both parasite physiology and host defence mechanisms being keys to understanding disease patterns.

Br J Neurosurg, 2001 Jun, 15(3), 265 - 9
Mycobacterium chelonae lumbar spinal infection; Suttner NJ et al.; A case report of a previously healthy adult patient with a lumbar spinal extradural abscess due to Mycobacterium chelonae is presented . His course of treatment was complicated by recurrent psoas abscesses, as well as multiantibiotic resistance, requiring multiple surgical drainage procedures and antibiotic changes over a 33-month period . Cure was achieved only after aggressive surgical debridement of the abscess.

J Lab Clin Med, 2001 Aug, 138(2), 101 - 6
Inhibition of mesothelioma cell growth in vitro by doxycycline; Rubins JB et al.; Malignant mesothelioma causes profound morbidity and nearly universal mortality that is often refractory to conventional treatment modalities of aggressive surgery, radiotherapy, or chemotherapy . Doxycycline, a commonly used antibiotic, has anti-tumor activity against several malignancies, but its anti-tumor effects on malignant mesothelioma have not been evaluated . We report here that concentrations of doxycycline achievable in serum with typical oral doses had cytostatic effects to varying extent on all eight of the mesothelioma cell lines studied but did not affect normal lung fibroblasts . Doxycycline inhibited the production of mitochondrial cytochrome c oxidase, especially in mesothelioma cells more sensitive to its cytostatic effects, and directly inhibited gelatinase A activity; both of these activities are putative mechanisms for the cytostatic activity of doxycycline in other tumor cells . Thus doxycycline may have a role as adjuvant therapy for malignant mesothelioma.

Injury, 2001 Jul, 32(6), 461 - 4
Current cementing techniques in hip hemi-arthroplasty; Scott S et al.; To assess the use of modern cementing techniques in hip hemi-arthroplasty a postal questionnaire was sent during 1998 to all British Orthopaedic Training Association (B.O.T.A.) members regarding use of cement, type of cement, bone preparation and cementing technique . The results of this survey were compared to a similar survey in 1994 to assess any change in practice . Two hundred and eighty-six trainees responded to the 1998 survey, 352 to the 1994 survey . The use of uncemented prostheses had decreased from 31.3 in 1994 to 21.7% in 1998 . Normal viscosity Palacos cement remains the most common cement in use, 64.3% in 1998 . The use of antibiotic loaded cement has increased from 53.7 in 1994 to 67.9% in 1998 . For bone preparation 47.3% of trainees in 1998 used a modern technique (syringe irrigation/pulsed lavage, brushing, gauze packing) compared to 35.1% in 1994 . Modern cement insertion (retrograde gun, cement restriction and sustained pressure) was carried out by 39.3% in 1998 compared to 28.5% in 1994 . Overall 27.2% of trainees used modern cementing techniques in hip hemi-arthroplasty, compared to 19.4% in 1994 . Modern cementing techniques are used by a minority of British orthopaedic trainees, but in comparison to 1994 their use has increased.

J Theor Biol, 2001 Aug 21, 211(4), 365 - 75
Pesticide resistance: can we make it a renewable resource?
Pittendrigh BR, Gaffney PJ.
Negative cross-resistance (NCR) occurs when a mutant allele confers (i) resistance to one toxic chemical and (ii) hyper-susceptibility to another . Sequential deployment of NCR toxins is useful for insect control in few situations (Pittendrigh et al., 2000) . Using Monte Carlo simulations, we investigated the concurrent use of a pair of NCR toxins to control a hypothetical insect pest population . When the toxins killed more heterozygotes than homozygotes, the resistance allele became either extremely common or rare depending on starting allelic frequency . If the NCR toxins did not kill the two homozygous groups equally, then the toxin with lesser toxicity eventually played a greater role in the control of the pest population . Based on our results, we present an approach for the systematic development of an NCR toxin after the commercial release of the first toxin . First, large-scale screens are performed to find chemicals that kill the resistant homozygous insects, but not the susceptible ones . Chemicals that preferentially kill resistant insects are then tested for toxicity to the heterozygotes . Those highly toxic to both homo- and heterozygotes are given the highest priority for development . This screen can be adapted to identify compounds useful in controlling antibiotic-, herbicide- or fungicide-resistant organisms .

J Am Acad Orthop Surg, 2001 Jul-Aug, 9(4), 219 - 26
Wound irrigation in musculoskeletal injury; Anglen JO; Wound irrigation to remove debris and lessen bacterial contamination is an essential component of open fracture care . However, considerable practice variation exists in the details of technique . Volume is an important factor; increased volume improves wound cleansing to a point, but the optimal volume is unknown . High-pressure flow has been shown to remove more bacteria and debris and to lower the rate of wound infection compared with low-pressure irrigation, although recent in vitro and animal studies suggest that it may also damage bone . Pulsatile flow has not been demonstrated to increase efficacy . Antiseptic additives can kill bacteria in the wound, but host-tissue toxicities limit their use . Animal and clinical studies of the use of antiseptics in contaminated wounds have yielded conflicting outcomes . Antibiotic irrigation has been effective in experimental studies in some types of animal wounds, but human clinical data are unconvincing due to poor study design . There are few animal or clinical studies of musculoskeletal wounds . Detergent irrigation aims to remove, rather than kill, bacteria and has shown promise in animal models of the complex contaminated musculoskeletal wound.

J Bone Joint Surg Br, 2001 Jul, 83(5), 691 - 5
Cefuroxime-impregnated cement at primary total knee arthroplasty in diabetes mellitus . A prospective, randomised study; Chiu FY et al.; We have performed a prospective single-blinded randomised study to evaluate the role of antibiotic-impregnated cement in the prevention of deep infection at primary total knee arthroplasty (TKA) in patients with diabetes mellitus . We studied prospectively 78 arthroplasties performed for osteoarthritis in such patients . They were randomly separated into two groups . In group 1 (41 knees), cefuroxime-impregnated cement was used while in group 2 (37 knees) cefuroxime was not added to the cement . The preoperative, intraoperative and postoperative management was the same for both groups . The mean follow-up was 50 months (26 to 88) . There were no cases of deep infection in group 1, but five (13.5%) occurred in group 2 (p = 0.021) . We conclude that cefuroxime-impregnated cement is effective in the prevention of deep infection at primary TKA in patients with diabetes mellitus.

Dent Traumatol, 2001 Feb, 17(1), 27 - 35
In vitro viability, mitogenicity and clonogenic capacities of periodontal ligament fibroblasts after storage in four media supplemented with growth factors; Ashkenazi M et al.; The choice of storage medium for preserving traumatically avulsed teeth is important for the success of future replantation . The objective of this study was to evaluate the effectiveness of growth factors (IGF-1 and PDGF-BB) when added to storage media in preserving the functional abilities of cultured periodontal ligament fibroblasts (PDLF) . The evaluated storage media were: ViaSpan, Hanks' balanced salt solution (HBSS), alpha minimal essential medium (alpha MEM), and alpha MEM supplemented with FCS and antibiotic (alpha MEM-S) . PDLF were obtained from explants of human healthy extracted teeth . Plates with confluent PDLF were soaked in the various media supplemented with IGF-1 (10 ng/ml) and PDGF-BB (4 ng/ml) for 2, 8 and 24 h at room temperature (24 degrees C) . The control group was incubated with the examined storage media without growth factors at 24 degrees C . An additional control group was incubated with culture medium at 37 degrees C without growth factors . After incubation, the viability of the cells was determined by Trypan blue exclusion test . Viable cells were then analyzed for mitogenic (with thymidine) and clonogenic (by culturing one cell/well) capacities . Storage of PDLF with growth factors (GF) for 2, 8 and 24 h decreased their vitality by only 3% (not statistically significant) . The mitogenicity of PDLF stored for 2, 8 and 24 h in various media with GF was statistically comparable to that of the control group . Generally, the highest mitogenic capacity of PDLF stored with or without GF was found after 8 h of storage . Increasing the storage period to 24 h decreased the mitogenic capacity of the cells stored with GF by only 10-40% compared to the control group . In contrast, the clonogenic capacity of PDLF stored with GF increased with increasing storage periods by 100-300%, and the highest clonogenic capacity was found in most storage media after 24 h of storage with GF . The highest clonogenic and mitogenic capacities were found in cells stored in HBSS followed by alpha MEM-S . The mitogenic and clonogenic capacities of PDLF stored in various media supplemented with GF for 2-8 h were generally lower than without GF supplementation . The mitogenic and clonogenic effects of GF-supplementation was observed only after 24 h of storage . After 24 h of storage with GF, the clonogenic capacity increased by 8-224% and the mitogenicity by 20-37%, except in cells stored in alpha MEM (-1%) . However, these differences were generally not statistically significant . In conclusion, the mitogenic and clonogenic effects of GF were observed only after 24 h of storage at room temperature . HBSS and alpha MEM-S supplemented with GF were the most effective media for preserving the viability, mitogenicity and clonogenic capacity of PDLF stored for 24 h at room temperature . For short periods of storage (2 and 8 h), HBSS and alpha MEM-S without GF were preferable.

Eur J Pediatr, 2001 Jul, 160(7), 455 - 6
Acute idiopathic scrotal oedema: four cases and a short review; van Langen AM et al.; We report four cases of acute idiopathic scrotal oedema, an underreported cause of acute painless or moderately painfull swelling and erythema of the scrotum in young boys . It is a self-limiting disease and to prevent unnecessary surgical exploration or antibiotic therapy, it is very important to distinguish acute idiopathic scrotal oedema from more serious diseases.

Pneumonol Alergol Pol, 2001, 69(1-2), 93 - 6
{Recurrent pneumothorax in a child with Langerhans' cell histiocytosis}; Bubala H et al.; We are presenting a 16 months old boy, who has been previously developing normally, physically very active, and who suddenly developed right-sided pneumothorax with infiltrations in both lungs, initially defined as inflammatory . After placing suction drainage of the pleural cavity and antibiotic administration the child's condition improved quickly . The infiltration changes still remained in lungs arousing a suspicion of fibrocystic changes . During an attempt at changing the drainage into a water one, the symptoms of pneumothorax with hypertension increased again . A minithoracotomy with an edge resection of segment 4 and pleurectomy were performed, relating to the histopathological test of the sample, Largenhans' cell histiocytosis was diagnosed . The symptoms of diabetes insipidus appeared . The treatment according to the program DAL-HX83/90 modified by the Polish Group for Leukaemia and Malignant Lymphoma was introduced . During the treatment inducing remission a pneumothorax occurred two more times.

J Clin Microbiol, 2001 Aug, 39(8), 2755 - 9
Detection of precytopathic effect of enteroviruses in clinical specimens by centrifugation-enhanced antigen detection; Lipson SM et al.; Rapid enterovirus detection is important for decisions about antibiotic administration and length of hospital stay . The efficacy of rapid antigen detection-cell culture amplification (Ag-CCA) was evaluated with monoclonal antibodies (MAbs) 5-D8/1 (DAKO) and Pan-Enterovirus clone 2E11 (Chemicon) with 10 poliovirus, echovirus, and coxsackievirus type A and B stock isolates and College of American Pathologists check samples . By using Ag-CCA technology, MAb 2E11 was more sensitive than 5-D8/1 at detecting a greater number of stock isolates at or past tube (cytopathic effect {CPE}) culture (TC) end points . The efficacy of Ag-CCA in the clinical setting was subsequently confirmed with 273 consecutively freshly collected nasopharyngeal aspirate or swab specimens, rectal swab, and cerebrospinal fluid specimens during the 1999 enterovirus season . All specimens were tested by Ag-CCA in parallel with rhesus monkey kidney (RhMk), MRC-5, and A549 conventional TCs . Approximately 60% of field specimens were additionally tested with Hep-2 and HNK conventional TCs . Sixty-two percent of the clinical specimens tested were Ag-CCA positive after 48 h . Among 51 isolates, the mean time to CPE or culture confirmation was 5.5 days (range, 2 to 18 days) . After 48 h, Ag-CCA achieved sensitivity, specificity, and positive and negative predictive values of 62, 100, 100, and 93%, respectively . During the same period, TC-CPE displayed test parameters of 12, 100, 100, and 85%, respectively . After 5 days, the sensitivity and specificity of Ag-CCA increased to 92 and 98%, respectively . Within the same period, isolation attained sensitivity and specificity of 52 and 100%, respectively . Although Ag-CCA displayed slightly reduced sensitivity and reduced specificity compared with conventional cell culture after 14 days, the markedly superior 48-h enterovirus Ag-CCA detection rate supports incorporation of this assay into the routine clinical setting.

Cornea, 2001 Aug, 20(6), 661 - 3
Cat's tooth keratitis: human corneal infection with Capnocytophaga canimorsus; Chodosh J; PURPOSE: To describe a patient with keratitis caused by Capnocytophaga canimorsus after traumatic injury with a cat's tooth . METHODS: Case report and review of the literature . RESULTS: Sixteen months after onset of infection, the patient regained 20/30 vision in the affected eye . However, he required 7 months of antibiotic therapy to eliminate the infection . CONCLUSION: C . canimorsus keratitis may follow penetrating corneal injury and wound contamination with cat saliva and may be recalcitrant to topical antibiotic therapy.

Cornea, 2001 Aug, 20(6), 619 - 21
Epiphora caused by conjunctivochalasis: treatment with transplantation of preserved human amniotic membrane; Georgiadis NS et al.; PURPOSE: To present our experience with the use of preserved human amniotic membrane on patients with epiphora caused by conjunctivochalasis . METHODS: Twelve patients, seven women and five men, ages ranging from 56 to 72 years (mean, 61 years) were referred to our Cornea Service with chronic epiphora . In all patients, no punctal ectropion was present, the lacrimal pathway was patent, and the dye disappearance test was abnormal . All patients had already undergone various therapies including multiple irrigations of the lacrimal system, antibiotic drops, steroid drops, and artificial tear drops . In all patients, conjunctivochalasis, which was not previously diagnosed, was evident on slit-lamp examination . After surgical removal of the excess conjunctiva, preserved human amniotic membrane was placed over and sutured with 10-0 nylon continuous suture to the free conjunctival edges . During the postoperative period, artificial tear drops and steroid/antibiotic drops were applied . RESULTS: Improvement of the epiphora was evident from the first postoperative day . After removal of the suture 10 to 15 days (mean, 12 days) after surgery, no patient complained of epiphora . The dye disappearance test was normal . During the follow-up period, which ranged from 6 to 11 months (mean, 8 months), no patient complained of epiphora and no conjunctivochalasis was detected in the area in which human amniotic membrane was transplanted . CONCLUSION: In our experience, transplantation of preserved human amniotic membrane greatly improved symptoms of epiphora caused by conjunctivochalasis . Continued education of the general ophthalmologists concerning this condition is required.

Appl Environ Microbiol, 2001 Aug, 67(8), 3603 - 9
The phosphinomethylmalate isomerase gene pmi, encoding an aconitase-like enzyme, is involved in the synthesis of phosphinothricin tripeptide in Streptomyces viridochromogenes; Heinzelmann E et al.; Streptomyces viridochromogenes Tu494 produces the antibiotic phosphinothricin tripeptide (PTT) . In the postulated biosynthetic pathway, one reaction, the isomerization of phosphinomethylmalate, resembles the aconitase reaction of the tricarboxylic acid (TCA) cycle . It was speculated that this reaction is carried out by the corresponding enzyme of the primary metabolism (C . J . Thompson and H . Seto, p . 197-222, in L . C . Vining and C . Stuttard, ed., Genetics and Biochemistry of Antibiotic Production, 1995) . However, in addition to the TCA cycle aconitase gene, a gene encoding an aconitase-like protein (the phosphinomethylmalate isomerase gene, pmi) was identified in the PTT biosynthetic gene cluster by Southern hybridization experiments, using oligonucleotides which were derived from conserved amino acid sequences of aconitases . The deduced protein revealed high similarity to aconitases from plants, bacteria, and fungi and to iron regulatory proteins from eucaryotes . Pmi and the S . viridochromogenes TCA cycle aconitase, AcnA, have 52% identity . By gene insertion mutagenesis, a pmi mutant (Mapra1) was generated . The mutant failed to produce PTT, indicating the inability of AcnA to carry out the secondary-metabolism reaction . A His-tagged protein (Hispmi*) was heterologously produced in Streptomyces lividans . The purified protein showed no standard aconitase activity with citrate as a substrate, and the corresponding gene was not able to complement an acnA mutant . This indicates that Pmi and AcnA are highly specific for their respective enzymatic reactions.

J Med Chem, 2001 Aug 2, 44(16), 2536 - 43
Design, synthesis, DNA binding, and biological evaluation of water-soluble hybrid molecules containing two pyrazole analogues of the alkylating cyclopropylpyrroloindole (CPI) subunit of the antitumor agent CC-1065 and polypyrrole minor groove binders; Baraldi PG et al.; We have synthesized and evaluated a series of hybrids, denoted 22--27, for in vitro cytotoxic activity against a variety of cancer cell lines . These hybrids represent a molecular combination of polypyrrole minor groove binders structurally related to the natural antitumor agent distamycin A and two pyrazole analogues of the left-hand segment called cyclopropylpyrroloindole (CPI) of the potent antitumor antibiotic (+)-CC-1065 . These novel water-soluble hybrids have been designed to enhance the minor groove binding ability of alkylating units 20 and 21, which should increase their clinical appeal by overcoming the administration problems of (+)-CC-1065 derivatives . The DNA alkylating and cytotoxic activities against several tumor cell lines are reported and discussed in terms of their structural differences in relation to both the number of N-methyl pyrrole rings and the type of the alkylating unit tethered to the oligopeptidic frame . It may be noted that, in general, and especially for 22--24, the cytotoxicity of the hybrids was much greater than that of the alkylating units alone . In only one case, compound 27, did the hybrid have cytotoxic activity comparable to that of the alkylating unit alone against FM3A/0 cells . The broadest spectrum of activity and greatest potency was shown by the hybrid 24, in which the alkylating unit 20 and the deformyl distamycin A are tethered by 1-methyl 2,5-dicarbonyl pyrazole, with IC(50) values for the different tumor cell lines ranging from 7 to 71 nM . For compounds 22--24, the increase of the length of the pseudopeptidic moiety from one to three N-methylpyrrole residues led to an increased cytotoxicity . Among the hybrids tested for their inhibitory effects on the proliferation of murine L1210 leukemia cell line, compound 24 proved to be the most active (IC(50) = 7.4 nM), and in the sequencing gel experiments, it showed the strongest and most highly sequence-specific DNA alkylation activity . For compounds 22-24, the sequence specificity of DNA alkylation appears to be affected by the modification of the number of pyrrole rings, and the correlation between cytotoxicity and alkylation pattern suggests that 24 exerts its cytotoxicity through DNA sequence-specific alkylation of the third adenine located in the sequence 5'-ACAAAAATCG-3' . The two other hybrids 22 and 23 were slightly less active for tumor cell proliferation, with IC(50) values of 58 and 19 nM, respectively . With only one exception, none of the compounds was endowed with antiviral activity at subtoxic concentrations . Compound 24 inhibited the effect of vaccinia virus at a concentration that was significantly lower than its minimum cytotoxic concentration for the E(6)SM host cells . These compounds gave distinct patterns of alkylation in AT-rich sequences, indicating that minor structural changes produced marked alterations in sequence selectivity.

Presse Med, 2001 Jun 16-23, 30(21), 1076 - 81
{Oxidative stress and human disease . Current knowledge and perspectives for prevention}; Lehucher-Michel MP et al.; DYNAMIC BALANCE: The antibiotic status of the human organism results from the dynamic balance between the antioxidant system and the production of reactive oxygen species . Oxidative stress occurs when this balance shifts in favor of pro-oxidants as can occur in several disease situations . ROS: Part of the oxygen used by cells is transformed into toxic metabolites, reactive oxygen species (ROS), which can be the cause or consequence of tissue and molecular disorders . Some of the most prominent diseases linked with oxidative stress include atherosclerosis, cancer, allergy, neurodegenerative diseases, Parkinson's disease . PERSPECTIVES FOR PREVENTION: Actions designed to prevent the environmental cause, such as eviction of a exposure to toxins or a change in eating habits, can be an effective means of reducing the lesions induced . Study of total antioxidant potential could be quite useful for detecting and monitoring environmental damage and for clinical follow-up . It could also help in determining, for each individual, the negative or positive development of a therapy on the anti-free radical action . Treatments must be personalized according to the tested response.

Presse Med, 2001 Jun 16-23, 30(21), 1049 - 54
{Acute sinusitus in adults . Management by general practitioners}; Ferrand PA et al.; OBJECTIVE: Acute sinusitis is a common condition encountered in general practice and raises the question of appropriate management . Sufficient data are still lacking in the literature to provide a fully satisfactory response . METHODS: We conducted a survey among 193 physicians representative of the general practitioners in France to collect 755 cases of acute sinusitis treated in the outpatient setting from January 6 through March 15, 1999 . We recorded clinical features and therapeutic management . RESULTS: Pain was the predominant clinical sign (97% of the patients) . Facial pain with a highly suggestive localization and aggravated by pressure and headache were the most frequent . Most of the patients also had a nasal symptom (77%) and an infectious context (90%) . Three circumstances had been pre-defined by the experts: unique acute sinusitis, acute episode of chronic sinusitis, and recurrent acute sinusitis . In 67% of the cases of unique acute sinusitis, the diagnosis of the general practitioner was confirmed a posterori by the experts . Few complementary tests were ordered (in 17% of the patients) mainly in fragile patients and mainly limited to a radiography of the sinus (81% of the complementary tests ordered) . An oral antibiotic was almost always prescribed (96% of the patients) although antibiotics comprised only 29% of all prescriptions . General corticosteroid therapy (41%), local treatment (73%) and anti-cough or expectoration medications (52%) were also prescribed . Despite the painful nature of sinusitis, analgesics were only prescribed for 36% of the patients . CONCLUSION: This observational survey enabled us to describe the diagnostic and therapeutic strategy used by French general practitioners for acute sinusitis in adults . There was general agreement on the strategy that was well adapted to the patient profiles . An evaluation of the different classes of drugs prescribed, and their efficacy in the outpatient setting, that remains to be determined, was not however attempted.

Ophthalmic Epidemiol, 2001 Jul, 8(2-3), 163 - 80
Understanding the community perspectives of trachoma: The Gambia as a case study; Ajewole JF et al.; Trachoma has justifiably attracted an incredibly large amount of research interest and literature over the last several decades . Perhaps, the area which is least explored is the social aspect of the disease . Most of the major constraints to trachoma control on the global scale appear to be concerned with this aspect of the disease . Recently, a study was conducted in The Gambia with the aim of highlighting the socio-cultural determinants of trachoma . We applied qualitative methods of Focus Group Discussion and Semi-structured interview to explore the local people's concepts of the disease among two traditional ethnic groups, the Jolas and the Manjagos, in five rural communities . Our results show that there appears to be a poor understanding of the chronic nature of the active inflammatory phase of trachoma among the local people . But more importantly, there is a lack of mental connection between this childhood infection and blindness resulting from trichiasis in adults . This probably explains why it is difficult for the people in these communities to see the need for prolonged use of antibiotic eye ointment as required in the treatment of active inflammatory trachoma . Moreover, the local concepts about the cause(s) of the disease tend to compel the people to seek the traditional herbal remedies first, though there is adequate knowledge and experience among them that modern methods of treatment may produce cure, as in the case of corrective lid surgery for trichiasis . This ambivalent attitude of the people to health services appear to be a universal phenomenon in many local communities in Africa, and perhaps hinges on the local people's perspective of the disease, which varies from place to place . We conclude that for any intervention strategy to achieve the set goals of eliminating trachoma in spite of these constraints, community support and participation is essential, and in order to achieve this, the health care provider needs to have a better understanding of the community perspectives of the disease.

Curr Opin Pulm Med, 2001 Jul, 7(4), 193 - 7
Management of parapneumonic pleural effusion; Lim TK; Parapneumonic pleural effusion is a common and potentially serious complication of pneumonia . The management of parapneumonic pleural effusion involves early diagnosis, adequate empiric antibiotic cover, and appropriate risk categorization . High-risk patients require safe and expedient drainage of the infected pleural space . The management options include thoracentesis, tube thoracostomy, adjunctive intrapleural fibrinolytic therapy, and surgical drainage . The methods of surgical drainage include thoracoscopy, thoracotomy, and decortication . The relative clinical efficacy of these treatment options has been studied in a small number of controlled clinical trials, the results of which have been systematically reviewed by expert panels . Based on the limited clinical evidence, expert reviewers were unable to recommend a best method of pleural drainage . However, the consensus is that an aggressive approach with early surgical drainage results in shorter hospital stays and may be more cost-effective than conservative management . This review discusses the clinical evidence and describes an aggressive sequential management strategy that combines intrapleural fibrinolysis with early surgical drainage.

Equine Vet J, 2001 Jul, 33(4), 366 - 70
A study of ten cases of focal peritarsal infection as a cause of severe lameness in the thoroughbred racehorse: clinical signs, differential diagnosis, treatment and outcome; Pilsworth RC et al.; The differential diagnoses of tarsal joint infection, fracture and peritarsal focal infection are of particular importance in practice . The objective of the present report is to provide additional clinical data to assist in the understanding of one of these conditions . The haematological parameters, clinical signs, treatment and outcome of 10 cases of severe lameness associated with peritarsal infection are reviewed . All horses had a significant rise in rectal temperature . The majority of cases (6/10) had haematological changes consistent with acute bacterial infection on the day of first examination . In the remaining cases these changes were not apparent on a blood sample taken on the first examination, but became so after 24 h . Nine out of 10 cases made a complete recovery on a regimen of i.v . antibiotic therapy, in conjunction with administration of nonsteroidal anti-inflammatory drugs and repeated forced exercise . One case developed osteomyelitis of the third and fourth metatarsal bones, but made a full recovery in due course . It is concluded that, in the majority of cases, prompt treatment with antibiotic therapy, analgesics and forced exercise results in complete resolution of the condition.

N Z Dent J, 2001 Jun, 97(428), 58 - 63
Bite injuries: pathophysiology, forensic analysis, and management; Liston PN et al.; Bites are serious injuries that constitute 1 percent of all emergency-department visits in the United States of America . Human bite injuries may lead to loss of function, infection, and gross disfigurement, and often are associated with interpersonal and sexual violence, and child abuse . Issues with infection from oral contaminants, tissue damage, and difficult surgical reconstruction make the management of human bite injuries a challenge . The unique nature of teeth and the bite marks they produce are invaluable in forensic pathology . A systematic and detailed evaluation of bite injuries should be performed by a forensic odontologist in order to provide the necessary information for forensic purposes . Management of human bite injuries includes wound debridement, surgery to repair or replace damaged tissue, and long-term antibiotic therapy.

J Emerg Nurs, 2001 Aug, 27(4), 335 - 9
Is routine heparin lock placement beneficial in the evaluation and treatment of febrile children?
Mahabee-Gittens EM, Grupp-Phelan J, Luria JW, Gonzalez del Rey JA.
INTRODUCTION: Nurses often use intravenous heparin locks (HL) with pediatric patients while obtaining laboratory studies to evaluate fever without a source . The purpose of the HL is to avoid an intramuscular injection if parenteral antibiotics are subsequently ordered . The objectives of this study were to determine if HL placement in patients undergoing laboratory evaluation for fever without a source (1) results in fewer injections and (2) is associated with increased use of antibiotics . METHODS: A retrospective chart review of ED patients aged 3 to 36 months was performed . Patients included in the review had fever with no identified source of infection, and a complete blood cell count and/or blood culture had been ordered . For analysis, patients who received an HL were compared with patients who did not receive an HL . RESULTS: A total of 439 patients had laboratory studies for fever without a source, with 345 (79%) in the HL group . No statistically significant differences were found in antibiotic administration, number of needle sticks, age, temperature, or white blood cell count between the groups . DISCUSSION: The use of an HL in young febrile ED patients did not change the total number of needle sticks or the likelihood of antibiotic administration.

Ann Emerg Med, 2001 Aug, 38(2), 129 - 34
Efficacy of eye patching for traumatic corneal abrasions: a controlled clinical trial; Le Sage N et al.; STUDY OBJECTIVE: We sought to evaluate the efficacy of eye patching in the treatment of traumatic corneal abrasions in terms of time to healing and reduction in pain and discomfort . METHODS: One hundred sixty-three patients presenting at the emergency department of a large university-affiliated hospital with traumatic corneal abrasions were included in this single-blind prospective controlled trial . Eligible patients were assigned to 1 of 2 treatment regimens: topical antibiotic ointment and occlusive patch over the affected eye (n=82) or topical antibiotic ointment 4 times a day without an occlusive patch (n=81) . Patients were reexamined every 24 hours until corneal healing occurred . Healing evaluation was performed by the emergency physician, using a slit lamp with fluorescein staining, without knowledge of the patient's assignment to a treatment group . The degree of discomfort was assessed at each visit by using a visual analog scale . RESULTS: Both treatment groups were similar regarding size of the corneal lesions, delay from trauma to first ED visit, presence of foreign body or siderosis, initial degree of discomfort, and presence of specific symptoms (irritation, foreign body sensation, photophobia, redness, and pain) . In the patched group, cumulative incidences of healing were 51%, 78%, and 92% after 1, 2, and 3 days, respectively, compared with 60%, 83%, and 88% in the nonpatched group . In the patched group, symptoms of initial discomfort decreased by 4.8, 4.1, and 5.5 cm after 1, 2, and 3 days, respectively, compared with 3.3, 5.1, and 6.5 cm in the nonpatched group . CONCLUSION: Eye patching does not appear to be beneficial in the treatment of traumatic corneal abrasions compared with topical antibiotic ointment.

Clin Chem, 2001 Aug, 47(8), 1553 - 8
Molecular detection of Mycobacterium tuberculosis: impact on patient care; Kaul KL; BACKGROUND: Nucleic acid amplification technologies such as PCR are revolutionizing the detection of infectious pathogens such as tuberculosis (TB) . Amplification technology offers the potential for the diagnosis of TB in a few hours with a high degree of sensitivity and specificity . However, molecular assays neither replace nor reduce the need for conventional smear and culture, speciation, and antibiotic sensitivity assays . METHODS: We undertook prospective studies of sputum samples to assess the performance of two PCR-based assays for the detection of TB as well as the impact of more rapid availability of test results on patient care . RESULTS: The sensitivity of both the in-house and Amplicor PCR assays was 100% for smear-positive sputa . For smear-negative sputa (two sputum samples collected during the first 24 h of hospitalization), the sensitivity was 85% for our in-house PCR assay and 74% for the Roche PCR assay . Approximately 10% of the smear- and culture-negative sputa yielded positive PCR results; however, more than one-half of these were positive with both the in-house and Amplicor assays, suggesting the presence of TB DNA or organisms . Several of these came from patients whose other samples grew Mycobacterium tuberculosis during the same admission, and others came from patients who had previously treated TB . Overall, the specificities of the in-house and Amplicor PCR assays in smear-negative patients were 86% and 93%, respectively . CONCLUSIONS: Molecular detection of slow-growing pathogens such as M . tuberculosis have the potential to improve clinical care through a dramatic reduction in the time required for detection and may provide substantial savings in the overall cost of care of a patient compared with conventional smear, culture, and speciation alone, despite the fact that conventional assays must still be performed for speciation of nontuberculous mycobacteria and for full assessment of antibiotic sensitivity.

Am J Gastroenterol, 2001 Jul, 96(7), 1968 - 76
Hepatic Encephalopathy; Blei AT et al.; 1 . Acute Encephalopathy in Cirrhosis A . GENERAL MEASURES . Tracheal intubation in patients with deep encephalopathy should be considered . A nasogastric tube is placed for patients in deep encephalopathy . Avoid sedatives whenever possible . Correction of the precipitating factor is the most important measure . B . SPECIFIC MEASURES i . Nutrition . In case of deep encephalopathy, oral intake is withheld for 24-48 h and i.v . glucose is provided until improvement . Enteral nutrition can be started if the patient appears unable to eat after this period . Protein intake begins at a dose of 0.5 g/kg/day, with progressive increase to 1-1.5 g/kg/day . ii . Lactulose is administered via enema or nasogastric tube in deep encephalopathy . The oral route is optimized by dosing every hour until stool evacuation appears . Lactulose can be replaced by oral neomycin . iii . Flumazenil may be used in selected cases of suspected benzodiazepine use . 2 . Chronic Encephalopathy in Cirrhosis i . Avoidance and prevention of precipitating factors, including the institution of prophylactic measures . ii . Nutrition . Improve protein intake by feeding dairy products and vegetable-based diets . Oral branched-chain amino acids can be considered for individuals intolerant of all protein . iii . Lactulose . Dosing aims at two to three soft bowel movements per day . Antibiotics are reserved for patients who respond poorly to disaccharides or who do not exhibit diarrhea or acidification of the stool . Chronic antibiotic use (neomycin, metronidazole) requires careful renal, neurological, and/or otological monitoring . iv . Refer for liver transplantation in appropriate candidates . For problematic encephalopathy (nonresponsive to therapy), consider imaging of splanchnic vessels to identify large spontaneous portal-systemic shunts potentially amenable to radiological occlusion . In addition, consider the combination of lactulose and neomycin, addition of oral zinc, and invasive approaches, such as occlusion of TIPS or surgical shunts, if present . Minimal or Subclinical Encephalopathy Treatment can be instituted in selected cases . The most characteristic neuropsychological deficits in patients with cirrhosis are in motor and attentional skills (60) . Although these may impact the ability to perform daily activities, many subjects can compensate for these defects . Recent studies suggest a small but significant impact of these abnormalities on patients' quality of life (61), including difficulties with sleep (62) . In patients with significant deficits or complaints, a therapeutic program based on dietary manipulations and/or nonabsorbable disaccharides may be tried . Benzodiazepines should not be used for patients with sleep difficulties.

Curr Pharm Biotechnol, 2000 Dec, 1(4), 313 - 23
Controlled delivery of biotechnological products; Conti S et al.; Peptides, proteins, and nucleotides or DNA fragments are the new generation of drugs . They are becoming attractive owing to the fast development of biotechnology . The admnistration of such molecules, however, may be a problem as sensitivity to temperature, instability at some physiological pH values, short plasma half-life, and high molecular dimension, which hinders the diffusive transport, make, at the moment, parenteral route the only possible way of administration of such molecules . Controlled drug delivery that comprises the development of new administration routes could be the answer to the problems for administration of biotechnological molecules . The rational of drug delivery is to change the pharmacokinetic and pharmacodynamic of drugs by controlling their absorption and distribution . Rate and time of drug release at absorption site could be programmed using a so called delivery system . Different technologies, such as chemical (pro-drugs), biological, polymers, lipids (liposomes, LDL), have been proposed to obtain controlled drug release . Also the use of new administration routes is part of controlled drug delivery . In fact, it could increase the drug absorption and reduce the effects of the active ingredient in those districts not interested in the therapy . Drug delivery systems allowing for an effective release in vivo of new biotechnological molecules, such as recombinant antiidiotypic antibodies with antibiotic activity, devoted to the treatment of pulmonary (tuberculosis and pneumocystosis) and mucosal (candidiasis) diseases are discussed under that perspective.

J R Soc Health, 2001 Jun, 121(2), 94 - 7
Changes and developments in cancer prevention; Hill MJ; During the last 125 years, there has been a massive decrease in mortality from infectious disease, as a result of improved public health and later as a result of antibiotic use . This has led to a consequent increase in life span from less than 50 (when cancer is rare) to more than 70 (when cancer is common) . As a result of these changes, cancer has moved from being a very minor cause of mortality in 1876 to one of the two major causes by 2000 . During the last century theories of the causation of cancer have changed progressively . In the early phase the main cause was thought to be environmental contamination with carcinogenic chemicals . Later, it was thought that all cancers were caused by cancers, then that cancer was caused by a breakdown in immune-surveillance . For 40 years we have known that tobacco smoke is a major cause of respiratory and other cancers, and preventive measures are currently having a dramatic effect on male lung cancer mortality . During the last 25 years it has become apparent that diet is the other major cause of cancer, but theories have moved steadily from a search for causal agents (e.g., too much fat) to protective agents (e.g., too little fruit and vegetable) . Currently it is accepted that all of the above theories contribute to the total cancer risk.

Arch Ophthalmol, 2001 Jul, 119(7), 1001 - 8
Risk factors for late-onset infection following glaucoma filtration surgery; Jampel HD et al.; OBJECTIVE: To determine the risk factors for late-onset infection following glaucoma filtration surgery . METHODS: We performed a case-control study comparing 131 cases of late-onset infection collected from 27 surgeons at 10 centers with 500 controls matched for date of surgery and surgeon . The criterion for the presence of infection was severe anterior chamber reaction occurring later than 4 weeks after surgery . An opaque bleb and positive culture results were not required for diagnosis . Risk factors were identified by univariate and multivariate logistic regression analyses . RESULTS: Some of the risk factors that were statistically significant in the multivariate model after adjusting for age, race, and sex were (1) performance of a full-thickness rather than a guarded procedure (risk ratio {RR}, 13.1; 95% confidence interval {CI}, 2.12-80.9), (2) filtration surgery performed without concurrent cataract surgery (RR, 2.25; 95% CI, 1.24-4.08), (3) use of mitomycin (RR, 2.48; 95% CI, 1.06-5.83), (4) intermittent use of antibiotics after surgery (RR, 2.10; 95% CI, 1.09-4.02), and (5) continuous use of antibiotics after surgery (RR, 5.94; 95% CI, 2.09-16.9) . CONCLUSIONS: Eyes undergoing full-thickness procedures or filtration surgery without cataract extraction are at increased risk for late infection . Intraoperative mitomycin and episodic or continuous antibiotic use after the postoperative period are associated with an increased risk of infection.

Med Pediatr Oncol, 2001 Jul, 37(1), 20 - 3
Pneumocystis carinii pneumonia during maintenance treatment of childhood acute lymphoblastic leukemia; Poulsen A et al.; BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a wellknown risk among patients with deficient T-cell function such as children treated for acute lymphoblastic leukemia (ALL) . The purpose of this study was to estimate the risk for PCP during maintenance treatment (MT) to identify patients at risk who could benefit from prophylaxis . PROCEDURE: We registered all episodes of PCP during MT in 71 children diagnosed between January 1992 and June 1997 with non-B-cell ALL at The Copenhagen University Hospital . Sulphametoxazole and trimetroprim (SMX/TMP) prophylaxis against PCP was given during induction and consolidation therapy but stopped prior to MT with oral methotrexate/6-mercaptopurine . Patients with standard (SR), intermediate (IR), and high risk (HR) ALL started MT at 3, 8, and 15 months from diagnosis, respectively . RESULTS: The HR group had a cumulated risk of 70% for developing PCP, whereas the risk for PCP in children with IR and the SR was 11 and 8%, respectively (P < 0.0001) . All but one of these 13 cases of PCP occurred within 8 months after cessation of SMX-TMP prophylaxis . CONCLUSIONS: The higher incidence of PCP among HR compared to non-HR patients following cessation of SMX/TMP prophylaxis probably reflects the significantly longer T-cell suppressive consolidation therapy in this group . The very low incidence of PCP during the later part of MT emphasizes that methotrexate/6-mercaptopurine MT have more impact on B-cell than on T-cell function . TMP/SMX prophylaxis should be recommended for all children treated for ALL .

Arch Dis Child, 2001 Aug, 85(2), 96 - 103
Does early detection of otitis media with effusion prevent delayed language development?
Butler CC, MacMillan H.
OBJECTIVE: To consider whether earlier detection of otitis media with effusion (OME) in asymptomatic children in the first 4 years of life prevents delayed language development . METHODS: MEDLINE and other databases were searched and relevant references from articles reviewed . Critical appraisal and consensus development were in accordance with the methods of the Canadian Task Force on Preventive Health Care . RESULTS: No randomised controlled trials assessing the overall screening for OME and early intervention to prevent delay in acquiring language were identified, although one trial evaluated treatment in a screened population and found no benefit . The "analytic pathway" approach was therefore used, where evidence is evaluated for individual steps in a screening process . The evidence supporting the use of tools for early detection such as tympanometry, microtympanometry, acoustic reflectometry, and pneumatic otoscopy in the first 4 years of life is unclear . Some treatments (mucolytics, antibiotics, steroids) resulted in the short term resolution of effusions as measured by tympanometry . Ventilation tubes resolved effusions and improved hearing . Ventilation tubes in children with hearing loss associated with OME benefited children in the short term, but after 18 months there was no difference in comparison with those assigned to watchful waiting . Most prospective cohort studies that evaluated the association between OME and language development lacked adequate measurement of exposure or outcome, or suffered from attrition bias . Findings with regard to the association were inconsistent . CONCLUSIONS: There is insufficient evidence to support attempts at early detection of OME in the first 4 years of life in the asymptomatic child to prevent delayed language development.

JAMA, 2001 Jul 18, 286(3), 335 - 40
Relationship between methodological trial quality and the effects of selective digestive decontamination on pneumonia and mortality in critically ill patients; van Nieuwenhoven CA et al.; CONTEXT: Although meta-analyses of randomized trials have shown that selective digestive decontamination (SDD) prevents nosocomial pneumonia in critically ill patients, the influence of trial quality on the effectiveness of SDD has not been rigorously evaluated . OBJECTIVE: To assess the methodological quality of individual studies of SDD and its relation to the reported effects on pneumonia and mortality . DESIGN: Thirty-two studies were identified in a MEDLINE and reference list search and their methodological quality was assessed using a scoring system (range, 0-13 points) based on allocation and concealment, patient selection, patient characteristics, blinding of the intervention, and the definition of pneumonia . MAIN OUTCOME MEASURE: Methodological quality of the primary trials and its effect on the relative risk reductions (RRRs) of SDD on pneumonia and mortality . RESULTS: The mean (SD) methodological quality score was 7.8 (2.9) (range, 1-11) . The RRRs ranged from -0.1 to 1.0 for pneumonia and from -0.1 to 0.6 for mortality . The methodological quality score was associated with the RRR for pneumonia so that for each quality-point added, the RRR decreased by 5.8% (95% confidence interval, 2.4%-9.3%) . No association between trial quality and the impact of SDD was found on mortality . Of the individual trial quality characteristics, patient selection, allocation of intervention, and blinding most strongly influenced the treatment effect . CONCLUSIONS: The inverse relationship between methodological quality score and the benefit of SDD on the incidence of pneumonia may have resulted in overly optimistic estimates of SDD in prior meta-analyses . This emphasizes the importance of rigorous trial design in evaluating preventive interventions in the intensive care unit.

Orthop Clin North Am, 2001 Jan, 32(1), 135 - 70
Soft tissue reconstruction for calcaneal fractures or osteomyelitis; Attinger C et al.; A systematic approach of the surgical management of a calcaneal fracture can minimize the potential of soft tissue complications . When reducing a closed calcaneal fracture, the incision used affects the postoperative complications . The L-shaped incision with the horizontal limb lying on the lateral glabrous junction ensures maximum blood flow to either side of the incision . Whether or not the wound can be closed primarily depends on the preexisting edema, the lost calcaneal height, and the delay between the fracture and reduction (Fig . 20) . The wrinkle test is a good indicator that the incision can be closed primarily if the amount of height restored is minimal . If the edema is too great, steps should be taken to reduce it sufficiently to allow successful wound closure . If the wound, after reduction, is too wide to allow primary closure, an ADM flap laterally or an AHM flap medially should be used . For larger defects, a free flap should be considered . The three important steps to reconstruction of soft tissue defects around the calcaneus include good blood supply, a infection-free wound, and the simplest soft tissue reconstructive option that covers the wound successfully . Adequate blood supply can be determined by the use of Doppler . If the supply is inadequate, revascularization is necessary before proceeding . Achieving a clean wound requires aggressive debridement, intravenous antibiotics, and good wound care . Adjuncts that can help in achieving a clean wound include topical antibiotics (silver sulfadiazine), the VAC, and hyperbaric oxygen . Osteomyelitis has to be treated aggressively . Any suspicious bone has to be removed . Only clean, healthy, bleeding bone is left behind . Antibiotic beads can be useful when there is doubt as to whether the cancellous bone is infection-free . The beads are not a substitute for good debridement, however . Soft tissue reconstruction ranges from delayed primary closure to the use of microsurgical free flaps (Fig . 21) . When bone or hardware is exposed, a muscle flap should cover the wound because of the extra blood supply it carries with it . The soft tissue option depends on the width of the wound . For wounds 1 cm wide or less, the options include allowing the wound to close by secondary intention (VAC), delayed primary closure, or a local muscle flap . For wounds 2 cm wide or less, allowing the wound to close by secondary intention (VAC) and a local muscle flap are the best options . For wider wounds, one has to assess whether the local muscle flap has sufficient bulk to close the defect . If it does, it is the simplest solution . If the local muscle is inadequate, a microsurgical free flap has to be used . The VAC sometimes can convert a large wound to a smaller wound so that a local muscle flap can be used . This procedure takes time, however, and adds to the cost of the repair.

Brief Bioinform, 2000 Sep, 1(3), 297 - 304
Visualising gene expression in its metabolic context; Wolf D et al.; Relative changes in mRNA as well as protein levels induced by sublethal doses of antibiotics on bacteria are measured and results visualised in the context of metabolic pathway diagrams . The mRNA levels present at a given time point after the addition of the antibiotic are measured using microarrays from Affymetrix . Additionally, the relative amount of each protein synthesised during 3 minute intervals sampled at the given times is measured using radio-labelling followed by two-dimensional polyacrylamide gel electrophoresis and the subsequent analysis of the images produced by exposure to a phosphorimager . Metabolic pathway diagrams are both constructed in-house and imported from KEGG (Kyoto Encyclopedia of Genes and Genomes) . Both protein and mRNA expression data can be displayed in the pathway diagrams such that the colour of the vectors or enzyme identifiers indicate the relative change in expression level and reproducibility.

Dig Surg, 2001, 18(3), 233 - 4
Arthritis as a rare extra-intestinal manifestation of acute sigmoid diverticulitis; Alba S et al.; BACKGROUND: A causal association between acute diverticulitis of the sigmoid colon and arthritis has rarely been reported . CASE REPORT: We report the case of a 60-year-old patient who developed migrating arthritis of the knee and ankle during the recurring episode of acute diverticulitis of the sigmoid colon . Treatment with NSAIDs and antibiotics had little effect on joint disease, but medical treatment was successful in reducing the diverticulitis-related symptoms . Arthritis promptly improved after surgical resection of the sigmoid colon, and 30 months later the patient is free of symptoms in the previously affected joints . CONCLUSIONS: Five cases of diverticulitis-associated arthritis have been reported . The similar case reported here reconfirms that joint disease has a limited response to medical approaches . Colon resection is recommended for patients with diverticulitis-associated arthritis which does not respond promptly to antibiotic therapy .

Br J Gen Pract, 2001 Jul, 51(468), 533 - 8
Otitis externa in UK general practice: a survey using the UK General Practice Research Database; Rowlands S et al.; BACKGROUND: Otitis externa is a common clinical problem in general practice and yet there are remarkably few data available on the demographic characteristics of patients with this condition and the approaches used by general practitioners (GPs) in the United Kingdom (UK) to manage it . AIM: To define the descriptive epidemiology of otitis externa in the general population, to describe the first-line drug treatment used by UK GPs, and to determine factors related to second disease episodes . DESIGN OF STUDY: Epidemiological data survey . SETTING: All cases of otitis externa occurring in 1997 in practices contributing data to the UK General Practice Research Database . METHOD: Data were extracted on age, sex, date of episode of otitis externa, treatment prescribed, co-existing diagnoses of eczema and diabetes, referral to ear, nose, and throat departments and occurrence of subsequent episodes of disease . Arbitrarily a second episode of disease was defined as persistence if it occurred at 28 days or fewer after the first episode and recurrence if it occurred at more than 28 days after the first episode . RESULTS: A diagnosis of otitis externa was common in all age groups and, except in the elderly, was more common in females than males . There was an increase in disease episodes at the end of the summer in all age groups except the 60 years and over group . In the majority of cases GPs prescribed ear drops (85%), but a significant proportion of patients were also prescribed oral antibiotics (21%) . Referral to secondary care was uncommon (3%) . Among patients prescribed ear-drop formulations, those containing both steroid and antibiotic or steroid alone were used most commonly and were associated with the lower rates of disease persistence but not recurrence . Among patients prescribed antibiotics, penicillins were prescribed most commonly . Disease persistence rates, and to a lesser extent disease recurrence rates, were higher in patients prescribed oral antibiotics . CONCLUSION: Otitis externa is a common condition and GPs can expect to see an excess of cases at the end of the summer . Topical ear drops are the most common treatment used in the UK . Patients prescribed steroid or steroid/antibiotic combination ear drops have fewer subsequent consultations for otitis externa over the following 28 days.

Curr Eye Res, 2001 Apr, 22(4), 286 - 94
Effect of external ocular surgery and mode of post-operative care on plasminogen, plasmin, angiostatins and alpha(2)-macroglobulin in tears; Lembach M et al.; PURPOSE . To determine whether corneal surgery and the mode of post-surgical treatment influence the distribution of plasminogen, plasmin, angiostatins and alpha(2)-macrogobulin in tear fluid . METHODS . Subjects underwent either photorefractive keratectomy (PRK), insertion of intra-stromal corneal rings (ICR), or cataract ablation followed by insertion of an intra-ocular lens (IOL) . Post-surgical treatment consisted of prophylactic use of antibiotic and anti-inflammatory agents followed either by patching for 24 hours, or covering the wounded cornea with a bandage soft contact lens . Open eye tear fluid (OTF) was obtained prior to surgery and 10 minutes after patch removal or 24 hours after surgery and thereafter with the bandage lens still in place . After centrifugation, supernatants and controls were western blot analyzed using a protocol designed to allow the simultaneous semi- quantitative detection of alpha2-macroglobulin, plasminogen, plasmin, angiostatins and interleukin-8 (IL-8) . RESULTS . No obvious differences were apparent in OTF recovered from contralateral control eyes compared to the surgical eyes in individuals who underwent PRK surgery and whose eyes were covered with a bandage contact lens . In contrast, OTF samples recovered 10 minutes after patch removal from all individuals contained elevated levels of alpha2-macroglobulin and a diverse mixture of elevated levels of plasminogen/plasmin, angiostatins and possibly a plasmin-a1-antiplasmin complex . All of these changes were seen, albeit to a lesser extent, in the patched control OTF samples . IL-8 could not be detected in any sample . The composition of the tear film returned to near normal on subsequent sampling 24 hours after patch removal . CONCLUSIONS . Patching results in a marked increase in the concentration of various proteins which could modulate inflammation and wound healing.

J Med Assoc Thai, 2001 Mar, 84(3), 445 - 7
Mitochondrial myopathy with respiratory dysfunction: a case report; Chotmongkol V et al.; A 50-year-old woman who presented with infective bronchiectasis and respiratory insufficiency was reported . Mitochondrial myopathy was diagnosed from a long history of chronic bilateral ptosis and external ophthalmoplegia with muscle wasting . Muscle biopsy revealed ragged-red fibers . After treatment with appropriate antibiotic and respiratory assistance, the patient improved and returned to her usual state of health.

Life Sci, 2001 Jun 15, 69(4), 455 - 67
Nitric oxide dependent and independent effects of in vitro incubation or endotoxin on vascular reactivity in rat aorta; Wylam ME et al.; We sought to delineate contributions of nitric oxide (NO) and other mechanisms to impairment of contraction and endothelium-dependent relaxation following prolonged in vitro incubation, endotoxin and interleukin-1 exposure in isolated rat aorta . Responses from freshly-dissected (control) rings +/-endothelium were compared with those from rings incubated in sterile, antibiotic containing medium +/- E . Coli endotoxin (LPS, 100 microg/ml) +/- interleukin-1 (IL-1, 40 ng/ml) at 37 degrees C for 20-24 h . In some experiments, medium included dexamethasone (DEX, 1 microg/ml), cycloheximide (10 microg/ml), or N(G)-nitro-L-arginine (NNLA, 10(-4)M) . After incubation, medium nitrite was measured . Incubation alone, without addition of inflammatory mediators, impaired contraction in an agonist-specific manner, by both NO-dependent and NO-independent mechanisms . Either LPS or IL-1 diminished contraction further, in a similarly heterogeneous manner . For example, contractions were changed in LPS-incubated endothelium-intact rings (vs . fresh controls) by -85%, +115%, -15%, -96%, and -37% for phenylephrine (PE), serotonin, prostaglandin F2alpha, angiotensin II, and U46619, respectively . NO synthase inhibition with NNLA either following, or during LPS incubation only partially normalized subsequent PE contractions, an effect which was smaller than that of DEX . Nitrite accumulation was inversely proportional to PE response, even though NO was not the sole mediator of LPS-impaired contraction . LPS and IL-1 nearly abolished ACh-induced relaxation, which was only mildly impaired by incubation alone . We conclude that prolonged incubation impaired vasoconstriction via both NO synthase induction and NO-independent mechanisms . LPS or IL-1 incubation impaired vasoconstriction further, primarily by NO-independent mechanisms . Moreover, vasoconstrictor responses following LPS varied with the agonist's ability to modulate endothelial NO release . These results are in accord with the failure of NO synthase inhibition to fully restore systemic vascular resistance indices in experimental endotoxemia or in hyperdynamic septic patients.

J Exp Bot, 2001 Jul, 52(360), 1409 - 15
Brefeldin A affects adhesion of zoospores of the green alga Enteromorpha; Callow ME et al.; Primary adhesion of zoospores of the green macroalga Enteromorpha to substrata involves a massive release of adhesive glycoproteins from Golgi-derived, membrane-bounded vesicles in the anterior region of the spore, followed by rapid curing . This process is sensitive to low concentrations (5-10 microg x ml(-1)) of the secretion-inhibiting antibiotic, brefeldin A (BFA) . The proportion of cells that settled in BFA was reduced by approximately 50%, but the effect was fully reversed by washing in seawater to remove the BFA . Ultrastructural observations showed that BFA caused the breakdown of Golgi stacks in the majority of cells examined . When settled cells were subjected to shear stress, a greater proportion of those settled in the presence of BFA were detached, compared with controls, indicating reduced adhesion strength in the presence of the antibiotic . The most likely reason for this is that strong adhesion to substrata either requires the synthesis of extra adhesive materials beyond those present in the swimming spore, or the secretion of an additional component required for adhesive curing . The novel use of atomic force microscopy in force modulation mode demonstrated that the adhesive secreted by most spores in the presence of BFA did not undergo the rapid curing process typical of control spores . However, some variation between zoospores was observed, with some cells showing no ultrastructural changes and normal adhesive curing . These results are discussed in relation to variations observed in the propensity and competence of spores to settle, which may be reflected in differential requirements for de novo synthesis and secretion of materials needed for full adhesion.

J Am Chem Soc, 2001 Apr 25, 123(16), 3784 - 9
The secondary structure of a membrane-modifying peptide in a supramolecular assembly studied by PELDOR and CW-ESR spectroscopies; Milov AD et al.; The new technique of pulsed electron-electron double resonance in electron spin-echo (PELDOR) in combination with the CW-ESR method has been used to investigate the secondary structure of a double spin-labeled peptide (the {TOAC-1,8}-analogue of the peptaibol antibiotic trichogin GA IV) that is hidden into a tetrameric supramolecular assembly of unlabeled peptide molecules . The magnetic dipole-dipole relaxation of spin labels has been experimentally studied in glassy solutions of the double-labeled peptide frozen to 77 K in a mixture of chloroform-toluene with an excess of unlabeled peptide . The PELDOR signal oscillations have been observed at high degrees of dilution with unlabeled peptide . The intramolecular distance between the spin labels of the peptide molecule in the aggregate has been determined from the oscillation frequency to be 15.7 A which is close to the value of (approximately equal to) 14 A calculated for a 3(10)-helical structure . Estimation of the fraction of this ordered secondary structure shows that about 19% of the peptide molecules in aggregates are folded in the 3(10)-helical conformation . The present experimental results are consistent with our molecular model presented in J . Am . Chem . Soc . 2000, 122, 3843-3848, wherein four amphiphilic 3(10)-helical peptide molecules form a vesicular system with the polar amino acid side chains pointing to the interior, and the apolar side chains, to the exterior of the cluster . The experimental data were compared with the results obtained with other techniques.

Ann Neurol, 2001 Jul, 50(1), 6 - 16
Neuroimmunophilins: novel neuroprotective and neuroregenerative targets; Guo X et al.; Cyclosporin A (CsA) and FK506 (tacrolimus) are immunosuppresants that are widely used in organ transplantation . CsA is an 11-member cyclic peptide, whereas FK506 is a macrolide antibiotic . Recently, these powerful and useful compounds have become of great interest to neuroscientists for their unique neuroprotective and neuroregenerative effects . These drugs and nonimmunosuppressive analogs protect neurons from the effects of glutamate excitotoxicity, focal ischemia, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic cell death . They also stimulate functional recovery of neurons in a variety of neurologic injury paradigms . These drugs exert their effects via immunophilins, the protein receptors for these agents . The immunophilin ligands show particular promise as a novel class of neuroprotective and neuroregenerative agents that have the potential to treat a variety of neurologic disorders.

Eur J Ophthalmol, 2001 Apr-Jun, 11(2), 183 - 6
Multilayer amniotic membrane transplantation in severe ocular graft versus host disease; Peris-Martinez C et al.; PURPOSE: To clarify the usefulness of multilayer amniotic membrane transplantation in an unusual case of calcareous corneal degeneration in a patient with graft-versus-host disease . METHODS: A 20-year-old Caucasian woman had bilateral calcareous corneal degeneration of one year of evolution, secondary to graft-versus-host disease . Treatment for both eyes with topical steroids and antibiotic ointment was not successful . Right eye had a spontaneous corneal perforation, and a three-layer circle amniotic membrane graft was applied to the whole cornea . RESULTS: During a follow-up period of 20 months we observed stability of the corneal epithelium and stroma . The amniotic membrane-covered area showed rapid epithelization, reduced inflammation and suppressed fibrosis formation . CONCLUSIONS: Multilayer amniotic membrane transplantation may be considered an alterantive for reconstructing the ocular surface in a patient with severe dry eyes and calcareous corneal degeneration, even with little perforation.

Biochem Biophys Res Commun, 2001 Jul 20, 285(3), 728 - 33
Marked reduction of Helicobacter pylori-induced gastritis by urease inhibitors, acetohydroxamic acid and flurofamide, in Mongolian gerbils; Ohta T et al.; Urease has been suggested to be essential for colonization and pathogenesis of Helicobacter pylori infection . In the present study, we evaluated the effects of urease inhibitors {acetohydroxamic acid (AHA) and flurofamide (FFA)} on H . pylori-induced gastritis in Mongolian gerbils . Animals were orally inoculated with H . pylori, and given urease inhibitors in their diet throughout the experimental period of six weeks or four weeks, starting from two weeks after H . pylori inoculation . With the administration of AHA at doses of 100, 500, and 2500 ppm throughout the experimental period, H . pylori-induced gastritis in animals was decreased in a dose-dependent manner, significantly so at 2500 ppm . Suppression of gastric lesions was also evident in animals administered 2500 ppm AHA after the H . pylori infection . Bacterial infection rates were reduced to 40-50% of the control value of 100%, by the highest dose of AHA . The potent urease inhibitor, FFA, also caused marked amelioration of H . pylori-associated gastritis on administration at 100 ppm throughout the six-week experimental period or for four weeks after H . pylori infection . Animals treated with FFA had few visible gastric lesions, and the proportion infected with H . pylori was reduced to less than 10% . Since antibiotic-resistant strains of H . pylori have become a serious problem, nonantibiotic urease inhibitors may be very useful to control H . pylori-associated gastroduodenal disease .

J Periodontol, 2001 Jun, 72(6), 824 - 30
Successful periodontal maintenance of a case with Papillon-Lefèvre syndrome: 12-year follow-up and review of the literature; Wiebe CB et al.; BACKGROUND: Various approaches to treating the periodontal condition associated with Papillon-Lefevre syndrome have been reported . These include oral hygiene instruction, use of mouthrinses, frequent debridement, multiple antibiotic regimens, periodontal surgery, extraction of hopeless teeth, and extraction of all deciduous teeth . Because Papillon-Lefevre syndrome is rare, most publications are case reports, and very few document long-term successful treatment of the periodontal condition . METHODS: In 1986, a 3.5-year-old Indo-Canadian male was diagnosed with Papillon-Lefevre syndrome and began periodontal treatment . Initial therapy consisted of debridement every 3 weeks, a 0.12% chlorhexidine mouthrinse, 2 regimens of metronidazole, and oral hygiene instruction for his parents . After 10 months it became apparent that the treatment was having little beneficial effect, since the periodontal destruction continued and teeth 51 and 61 exfoliated . At age 4, all remaining deciduous teeth were extracted and complete dentures inserted for the following 2-year edentulous period; then a 3-month maintenance schedule was maintained . RESULTS: The patient is now 17 years old and all his adult teeth are present with the exception of the third molars . His oral hygiene varies between moderate and good, with his most recent plaque score at 80% effectiveness . There are no probing depths greater than 4 mm, with the exception of the distal of the lower second molars where opercula are present . CONCLUSIONS: Extraction of all the deciduous teeth followed by a period of edentulousness may partially explain the fact that there has been no recurrent attachment loss in the permanent teeth up to age 17 . Other explanations are discussed as part of the literature review of Papillon-Lefevre syndrome.

Chir Ital, 2001 May-Jun, 53(3), 375 - 81
{Surgical treatment in acute cholecystitis emergencies}; Amendolara M et al.; The aim of the study was to demonstrate the importance of early laparoscopic cholecystectomy for acute cholecystitis, without "conservative" treatment (intravenous fluids and antibiotics for 48-72 hours) to reduce inflammation . Early laparoscopic cholecystectomy reduces bile duct injury and the percentage of conversion to open cholecystectomy . Thirty-five patients with acute cholecystitis were submitted to early laparoscopic cholecystectomy, equally divided according to sex . All patients were submitted to US scans preoperatively and operated on by surgeons skilled in emergency laparoscopic operative techniques . Laparoscopic cholecystectomy was always performed with 4 trochars and the use of a 30 degrees laparoscope . Technical modifications during early laparoscopic cholecystectomy were drainage and decompression with subsequent de-tension and distention of the gallbladder . These manoeuvres entailed the use of Babcock, Endopatch (Ethicon) atraumatic forceps . In the presence of acute gallbladder inflammation we dissect the gall-blader well with a suction-irrigation tube . In patients suspected of having common bile duct stones, biliary duct injuries and/or anatomical changes due to inflammation, we perform intraoperative cholangiography . Five patients had conversion to open cholecystectomy (14.2%), in two cases (5.7%) for concomitant choledochal stones, in two cases (5.7%) for biliary peritonitis and in the fifth case (2.8%) for severe empyema of the gallbladder . Laparoscopic cholecystectomy was performed in 20 patients for acute cholecystitis (57.1%), in 9 patients for empyema (25.7%) and in 6 patients for gangrenous cholecystitis . Four cases presented postoperative complications owing to bile leakage from the liver bed, treated with antibiotic therapy . One patient presented jaundice on day 30 after laparoscopy owing to inadequate positioning of the clips on the cystic duct, near the common bile duct; ERCP was performed with application of a prosthesis, which was removed after two months . Our experience and results support the validity of early laparoscopic cholecystectomy in the treatment of acute cholecystitis, because it reduces the postoperative length of hospital stay and hospital costs . Early treatment is always helpful for inflamed and oedematous tissue which favours dissection, while dense, fibrotic adhesions hinder regular dissection with a greater risk of injury to the biliary duct and and a higher conversion rate to open cholecystectomy.

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