Z Naturforsch {C}, 1999 May-Jun, 54(5-6), 325 - 32 Phytotoxic and photosynthetic activities of maduramicin and maduramicin methyl ester; Gutierrez-Lugo MT et al.; The polyether antibiotic maduramicin and its methyl ester derivative inhibited photophosphorylation and proton uptake in isolated spinach chloroplasts . Both compounds also enhanced basal and phosphorylating electron transport and stimulated Mg(2+)-dependent ATPase activity, therefore, they behave as uncouplers of photophosphorylation being the methyl ester derivative more potent than the parent compound . On the other hand, maduramicin inhibited germination and radicle elongation of several crop and weed species . In addition, the antibiotic caused phytotoxic injury and fresh weight reduction to 4-to-6 week old seedlings of two weed and two crop species when applied at 10(-4) M by foliar application in the greenhouse. J Cell Physiol, 1999 Sep, 180(3), 334 - 44 Chloramphenicol-induced mitochondrial dysfunction is associated with decreased transferrin receptor expression and ferritin synthesis in K562 cells and is unrelated to IRE-IRP interactions; Leiter LM et al.; Chloramphenicol is an antibiotic that consistently suppresses the bone marrow and induces sideroblastic anemia . It is also a rare cause of aplastic anemia . These toxicities are thought to be related to mitochondrial dysfunction, since chloramphenicol inhibits mitochondrial protein synthesis . We hypothesized that chloramphenicol-induced mitochondrial impairment alters the synthesis of ferritin and the transferrin receptor . After treating K562 erythroleukemia cells with a therapeutic dose of chloramphenicol (10 microg/ml) for 4 days, there was a marked decrease in cell surface transferrin receptor expression and de novo ferritin synthesis associated with significant decreases in cytochrome c oxidase activity, ATP levels, respiratory activity, and cell growth . Decreases in the transferrin receptor and ferritin were associated with reduced and unchanged message levels, respectively . The mechanism by which mitochondrial dysfunction alters these important proteins in iron homeostasis is not clear . A global decrease in synthetic processes seems unlikely, since the expression of the cellular adhesion proteins VLA4 and CD58 was not significantly decreased by chloramphenicol, nor were the message levels of beta-actin or ferritin . The alterations were not accompanied by changes in binding of the iron response protein (IRP) to the iron-responsive element (IRE), although cytosolic aconitase activity was reduced by 27% in chloramphenicol-treated cells . A disturbance in iron homeostasis due to alterations in the transferrin receptor and ferritin may explain the hypochromic-microcytic anemia and the accumulation of nonferritin iron in the mitochondria in some individuals after chloramphenicol therapy . Also, these studies provide evidence of a link between mitochondrial impairment and iron metabolism in K562 cells. Cardiovasc Surg, 1999 Jun, 7(4), 447 - 50 Gentamicin beads in vascular surgery: long-term results of implantation; Benaerts PJ et al.; The authors conducted a prospective study, with a subsequent review of case-notes and follow-up of patients, to review the results of insertion of gentamicin beads for the prevention and treatment of infection in vascular surgery . In particular, special reference was given to leaving chains of beads permanently implanted in the body . There were thirty-five patients in whom gentamicin beads were used in 62 sites . These were implanted completely in 45, left protruding for removal in 15 and in open wounds in two . Forty-two chains of beads were left permanently implanted, and these patients were followed up for 1-44 months (median 15) later . There was no further infection at 60% of the sites where gentamicin beads were used to treat proven graft sepsis, and 50% of sites in various sinuses . Infection developed at 16% of the sites where gentamicin beads were used prophylactically . Adverse effects were observed in three cases of long-term implantation: one chain of beads caused discomfort that required removal, the skin failed to heal over one chain, and one may possibly have caused a bypass graft to kink and occlude . In conclusion, gentamicin beads are a useful adjunct in the management of vascular graft infection and in prophylaxis for some high risk cases . Chains of beads can be implanted long term with few adverse sequelae. Cardiovasc Surg, 1999 Jun, 7(4), 398 - 401 The pharmacokinetics of a single dose of gentamicin (4 mg/kg) as prophylaxis in cardiac surgery requiring cardiopulmonary bypass; Lewis DR et al.; BACKGROUND: Cardiopulmonary bypass has complex effects on drug pharmacokinetics, which is important when considering the use of once-daily aminoglycoside regimens during cardiac surgery . AIM: To study the effects of cardiopulmonary bypass on the pharmacokinetics of a single dose of gentamicin (4 mg/kg) . PATIENTS AND METHODS: Nine patients undergoing valve replacement surgery were given a single dose of gentamicin (4 mg/kg) at induction of anaesthesia and blood was taken for assay at 0, O.5, 1, 1.5, 2, 2.5, 3, 4, 6, 10, 16, 22 and 24 h following administration . The mean (range) gentamicin Cmax was 18.7 (12.4-26.3) mg/litre . Three patients had concentrations of gentamicin after 24 h of > 1 mg/litre . During cardiopulmonary bypass, the mean (range) gentamicin half-life (t1/2) was 5.1 (2.0-15.1) h and post-bypass the t1/2 was 7.1 (3.0-13.9) h . CONCLUSION: There is significant correlation between the elimination t1/2 and length of cardiopulmonary bypass (r = 0.89, P < 0.01) . These results suggest that gentamicin excretion is delayed following cardiopulmonary bypass so that with dose regimens of > 4 mg/kg there is a risk of toxicity. Acta Derm Venereol, 1999 Jul, 79(4), 265 - 7 Minocycline modulation of alpha-MSH production by keratinocytes in vitro; Sainte-Marie I et al.; The anti-inflammatory mechanisms of minocycline, an antibiotic used in the treatment of the inflammatory component of acne, are only partially understood . In addition to inflammation due to cytokines (IL-1, IL-6, TNF-alpha, etc.), recent studies have shown that neuropeptide-mediated neurogenic inflammation may play an important role in cutaneous inflammation . The purpose of this study was to investigate minocycline-induced modulation of cutaneous production of alpha-melanocyte-stimulating hormone (alpha-MSH), a neuropeptide with known anti-inflammatory activity . Two different skin models were used: explants of inflammatory skin and reconstituted skin, both incubated with minocycline at different concentrations and for different time periods . Epidermal production of alpha-MSH, as evaluated by immunofluorescence and immunoperoxidase techniques, showed increased expression in both models . This neuropeptide, which has an anti-inflammatory activity (notably through production of IL-10, antagonism of IL-1 and inhibition of the chemotaxis of polymorphonuclear leukocytes), thus plays a role in the anti-inflammatory action of minocycline. FEBS Lett, 1999 Jul 16, 455(1-2), 140 - 4 Cloning and heterologous expression of a cDNA encoding 1-deoxy-D-xylulose-5-phosphate reductoisomerase of Arabidopsis thaliana; Schwender J et al.; Various plant isoprenoids are synthesized via the non-mevalonate pathway of isopentenyl diphosphate formation . In this pathway, 1-deoxy-D-xylulose 5-phosphate (DOXP), the first intermediate, is transformed to 2-C-methyl-D-erythritol 4-phosphate (MEP) by an enzyme which was recently cloned from Escherichia coli . In order to find a plant homologue of this 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) we cloned a cDNA fragment from Arabidopsis thaliana which has high homology to the E . coli DXR . By expression of this fragment in E . coli we could demonstrate that it encodes a protein which transforms DOXP to MEP . The antibiotic fosmidomycin specifically inhibits this DXR enzyme activity. J Arthroplasty, 1999 Jun, 14(4), 500 - 4 The role of intraoperative Gram stain in revision total joint arthroplasty; Della Valle CJ et al.; The ability to identify intraoperatively patients with an infected prosthesis at the time of a revision procedure assists the surgeon in selecting appropriate management . The results of 413 intraoperative Gram stains were compared with the results of operative cultures, permanent histology, and the surgeon's intraoperative assessment to determine the ability of Gram stains to identify periprosthetic infection . Gram staining correctly identified the presence of infection in 10 of the 68 cases that met study criteria for infection (sensitivity of 14.7%) . Four false-positive Gram stains were encountered . Intraoperative Gram stains do not have adequate sensitivity to be helpful in identifying periprosthetic infection and should not be performed on a routine basis . They may be helpful, however, in cases in which gross purulence is encountered to assist in the selection of initial antibiotic therapy . The use of intraoperative Gram staining alone is inadequate for ruling out infection at the time of revision total joint arthroplasty. Ann Pharm Fr, 1999 May, 57(3), 255 - 65 {The influence of steric crowding on the electrochemical reduction of amide groups in a pyridylcarboxamide seriesapplication to rote ction of amines in peptide synthesis}; Auzeil N; To gain a better understanding of the effect exerted by the 3-hydroxypicolinoyl residue on the antibiotic activity of Pristinamycin IA, the C-N bond of picolinamide was cleaved electrochemically . A mechanistic study demonstrated that the presence of the peptidic macrolactone M markedly modified the expected cathodic behavior of pyridylcarboxamides . In order to assess the influence of steric crowding exerted by M on this original behavior, we look for models using two different approachs . First, tertiary pyridylcarboxamides were used to increase steric hindrance at the amide nitrogen position; second, M was opened by ammonolysis to decrease steric crowding at the amide nitrogen position . The electrochemical behavior of the selected compounds is presented in the first and the second parts of this study . Determination of pyridine nitrogen basicity in an N-substituted-3-methoxypicolinamide series is treated in the third part as a useful probe to evaluate the intensity of steric crowding at the amide nitrogen position . Finally, in the last part of this work, we propose the use of the picolinoyl residue (C6H4N-CO-ou Pic) as a protecting group for amines in peptide synthesis. Structure Fold Des, 1999 Jul 15, 7(7), 817 - 27 Saccharide-RNA recognition in a complex formed between neomycin B and an RNA aptamer; Jiang L et al.; BACKGROUND: Aminoglycoside antibiotics can target RNA folds with micromolar affinity and inhibit biological processes ranging from protein biosynthesis to ribozyme action and viral replication . Specific features of aminoglycoside antibiotic-RNA recognition have been probed using chemical, biochemical, spectroscopic and computational approaches on both natural RNA targets and RNA aptamers identified through in vitro selection . Our previous studies on tobramycin-RNA aptamer complexes are extended to neomycin B bound to its selected RNA aptamer with 100 nM affinity . RESULTS: The neamine moiety (rings I and II) of neomycin B is sandwiched between the major groove floor of a 'zippered-up' G.U mismatch aligned segment and a looped-out purine base that flaps over the bound antibiotic . Specific intermolecular hydrogen bonds are observed between the charged amines of neomycin B and base mismatch edges and backbone phosphates . These interactions anchor 2-deoxystreptamine ring I and pyranose ring II within the RNA-binding pocket . CONCLUSIONS: The RNA aptamer complexes with tobramycin and neomycin B utilize common architectural principles to generate RNA-binding pockets for the bound aminoglycoside antibiotics . In each case, the 2-deoxystreptamine ring I and an attached pyranose ring are encapsulated within the major groove binding pocket, which is lined with mismatch pairs . The bound antibiotic within the pocket is capped over by a looped-out base and anchored in place through intermolecular hydrogen bonds involving charged amine groups of the antibiotic. J Comput Aided Mol Des, 1999 Jul, 13(4), 385 - 96 Conformational variety for the ansa chain of rifamycins: comparison of observed crystal structures and molecular dynamics simulations; Bacchi A et al.; The antibiotic activity (via inhibition of DNA-dependent RNA polymerase, DDRP) of rifamycins has been correlated to the conformation of the ansa chain, which can be described by means of 17 torsion angles defined along the ansa backbone . It has been shown that favourable or unfavourable conformations of the ansa chain in rifamycin crystals are generally diagnostic of activity or inactivity against isolated DDRP . The principles of structure correlation suggest that the torsional variety observed in rifamycin crystals should mimic the dynamic flexibility of the ansa chain in solution . Twenty-six crystal structures of rifamycins are grouped into two classes (active and non-active) . For each class the variance of the 17 ansa backbone torsion angles is analysed . Active compounds show a well-defined common pattern, while non-active molecules are more scattered, mainly due to steric constraints forcing the molecules into unfavourable conformations . The experimental distributions of torsion angles are compared to the torsional freedom of the ansa chain simulated by molecular dynamics calculations performed at different temperatures and conditions on rifamycin S and rifamycin O, which represent a typical active and a typical sterically constrained molecule, respectively . It is shown that the torsional variety found in the crystalline state samples the dynamic behaviour of the ansa chain for active compounds . The methods of circular statistics are illustrated to describe torsion angle distributions. Protein Expr Purif, 1999 Aug, 16(3), 405 - 9 Use of rifampicin in T7 RNA polymerase-driven expression of a plant enzyme: rifampicin improves yield and assembly; Kuderova A et al.; Expression systems based on high selectivity and activity of T7 RNA polymerase and presence of a strong T7 promoter have been commonly used for cloning and expression of various recombinant proteins in Escherichia coli . When the expression system is designed in such a way that the produced protein is not being transferred into periplasm, bacterial cells must be lysed in order to isolate and purify the protein . The final yield and quality of the synthesized protein then depend on various factors, protein size, amino acid sequence, solubility in cytoplasm, and folding requirements among them . The yield in the T7 RNA polymerase/promoter system can be positively influenced by use of rifampicin . In this report we demonstrate usefulness of the antibiotic in detail . We describe rifampicin-enhanced expression of a plant cytokinin-specific beta-glucosidase . Two bacterial cultures are compared, one expressing the enzyme without and one in the presence of rifampicin . The antibiotic not only increased the yield of the recombinant protein, which seems to be a general phenomenon, but also favored the final assembly of the protein's subunits into a catalytically active dimer form . Am J Ther, 1997 Feb-Mar, 4(2-3), 73 - 9 A study of the interaction between dirithromycin and astemizole in healthy adults; Bachmann K et al.; The effect of a standard regimen of dirithromycin, a macrolide antibiotic, on the single-dose pharmacokinetics of the H (1) receptor blocker astemizole was evaluated in a sample of 18 healthy young adults (nine males and nine females) . The study was conducted in a two-way cross-over fashion after the subjects had been randomly given either dirithromycin (two 250 mg tablets) or placebo (two tablets) every morning for 10 days . On the morning of the fourth dose of either dirithromycin or placebo each subject ingested a single 30-mg oral dose (three 10-mg tablets) of astemizole . The disposition kinetics of both astemizole and its major metabolite, N-desmethylastemizole, were characterized after measuring the concentrations of both analytes in the serum fraction of serial blood samples collected for 14 days after the astemizole dose . In addition, corrected QT (QT(c) ) intervals were estimated from electrocardiogram rhythm strips that were run 24 hours prior to the astemizole dose, 12 hours after the astemizole dose, and after the last treatment (dirithromycin or placebo) dose in both study periods . Pharmacokinetic parameters that were measured for both astemizole and N-desmethylastemizole during each treatment were: C(max), t(max), AUC (0-infinity), CL(oral), half-life, and volume of distribution (V) . None of the parameters for N-desmethylastemizole was different when comparing data by ANOVA from the dirithromycin treatment period with that of the placebo treatment period . On the other hand, during dirithromycin treatment astemizole CL(oral) was 34% slower, volume of distribution was 24% larger, and half-life was 84% longer . Generally, all QT ( c ) intervals did not appear to be affected by dirithromycin treatment . The changes in astemizole kinetics could not be attributed to its N-demethylation since the dispositional kinetics of N-desmethylastemizole were unaffected by dirithromycin . Therefore, it is difficult to ascertain the clinical significance of the changes in astemizole kinetics . Since there were no significant differences for mean QT(c) intervals and no effect of dirithromycin treatment on N-desmethylastemizole kinetics, it is unlikely that a standard regimen of dirithromycin would place a patient taking astemizole at an increased risk of torsade de pointes or related ventricular arrhythmias. J Mass Spectrom, 1999 Aug, 34(8), 813 - 9 Covalent and non-covalent dissociations of gas-phase complexes of avoparcin and bacterial receptor mimicking precursor peptides studied by collisionally activated decomposition mass spectrometry; van der Kerk-van Hoof A et al.; The gas-phase stability and reactivity of non-covalent complexes of avoparcin and bacterial receptor mimicking precursor peptides were probed by electrospray ionization mass spectrometry combined with collisionally activated decomposition (CAD) studies . The order of the gas-phase stabilities of these non-covalent complexes is different from the order of the stabilities of the same complexes in solution . The specific stereoselectivity observed in non-covalent binding in solution is not retained in the gas phase . The presence of a lysine residue in the bacterial receptor mimicking precursor peptides appears to promote the gas-phase stabilities of the antibiotic-peptide complexes . Complexes of avoparcin with receptor peptides containing a lysine residue are stabilized in the gas phase to such an extent that CAD of these non-covalent complexes proceeds through a competition between non-covalent and covalent fragmentation pathways . These results indicate clearly that the use of CAD mass spectra for the quantitative characterization of the stability of non-covalent complexes in solution should be applied with extreme caution . Neuroreport, 1999 Jul 13, 10(10), 2067 - 71 Effects of BDNF and NT-3 on hair cell survival in guinea pig cochlea damaged by kanamycin treatment; Ruan RS et al.; The aim of this study was to determine whether neurotrophic factors such as brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) would protect auditory hair cells from ototoxicity by aminoglycoside antibiotic . Twenty-seven Wistar guinea pigs were divided into three groups of nine animals each . BDNF and NT-3 (100 microg/ml) were delivered into the right scala tympani of guinea pig cochlea through a cannula-osmotic pump device . Artificial perilymph (AP) was used as control . Immediately after implantation of the device, each animal was given five successive doses of kanamycin (400 mg/kg) . At 15, 30 and 60 days after infusion, surviving inner and outer hair cells were counted at each turn of every cochlea with a Philips 515 scanning electron microscope . Multiple comparison tests were carried out among the groups, using ANOVA and Dunnett T3/Tukey HSD . Protective effects of NT-3 on hair cells were observed at 30 and 60 days after kanamycin injection . BDNF had no protective effect on hair cells at 15 and 60 days, but some at 30 days . This study suggests that NT-3 and BDNF may protect against cochlear hair cell damage caused by kanamycin treatment . Possible mechanisms for the otoprotective effects were discussed . No single mechanism postulated can explain fully the results seen in this study . It is possible that the mechanisms act in concert to produce the observed effects, or there are as yet undiscovered mechanisms or secondary messengers responsible for the otoprotective effects. Chest, 1999 Jul, 116(1), 222 - 30 Tick-borne pulmonary disease: update on diagnosis and management; Faul JL et al.; Ticks are capable of transmitting viruses, bacteria, protozoa, and rickettsiae to man . Several of these tick-borne pathogens can lead to pulmonary disease . Characteristic clinical features, such as erythema migrans in Lyme disease, or spotted rash in a spotted fever group disease, may serve as important diagnostic clues . Successful management of tick-borne diseases depends on a high index of suspicion and recognition of their clinical features . Patients at risk for tick bites may be coinfected with two or more tick-borne pathogens . A Lyme vaccine has recently become available for use in the United States . Disease prevention depends on the avoidance of tick bites . When patients present with respiratory symptoms and a history of a recent tick bite or a characteristic skin rash, a differential diagnosis of a tick-borne pulmonary disease should be considered . Early diagnosis and appropriate antibiotic therapy for these disorders lead to greatly improved outcomes. J Pept Res, 1999 May, 53(5), 501 - 6 Solid-phase total synthesis of polymyxin B1; Sharma SK et al.; The total solid-phase synthesis of polymyxin B1 (PMB1) has been achieved in 20% yield using the orthogonal protecting group N-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl-(Dde) . This report demonstrates that a complex peptide macrocycle can be synthesized in high yields using solid-phase synthesis . According to MS and HPLC, the synthetic peptide was identical to the naturally occurring antibiotic. Nippon Ishinkin Gakkai Zasshi, 1999, 40(3), 183 - 8 {A case of invasive aspergillosis in an amyloidosis patient}; Kawamura S et al.; A sixty-four-year-old male patient was admitted on 13 April 1995 with diagnosis of old pulmonary tuberculosis and pulmonary aspergilloma . He developed a tarry stool and frequent loose motion in early November 1995 . Histopathological findings of endoscopic biopsy from the duodenum and colon were suggestive of secondary amyloidosis . In spite of antibiotic and steroid pulse, he developed shock, and massive infiltration shadow appeared in chest X-ray . The patient died on 29 December 1995 . The postmortem examination in the specimens of the lung, heart, kidney, liver, and spleen revealed hyphae of Aspergillus sp . and in the specimens of the lung, kidney, spleen, esophagus, adrenal gland, and thyroid revealed amyloid . He was finally diagnosed as invasive aspergillosis with secondary amyloidosis. Nippon Ishinkin Gakkai Zasshi, 1999, 40(3), 129 - 33 {Evaluation of antimycotics in the elderly}; Fukayama M; Incidence and risk factors were analyzed in elderly patients with deep-seated mycosis . Twenty cases with candidiasis or aspergillosis were found in 1,663 autopsy cases . Intravascular catheters and administration of antibiotics were prominent risk factors for candidiasis as was steroid therapy . Leukocytopenia due to anti-cancer drugs caused aspergillosis . Preventive use of AMPH in patients with hematological malignancies or with steroid therapy was effective against mycosis . Although AMPH is also effective for almost all kinds of deep-seated mycosis, we rarely administered it to elderly patients because of its nephrotoxicity . The safe use of antimycotics requires checking drug sensitivity of causative fungi in a laboratory, and establishing the optimal dosage for patients with impaired renal function. Pediatr Pulmonol, 1999 Aug, 28(2), 89 - 93 Antireflux surgery in children suffering from reflux-associated respiratory diseases; Ahrens P et al.; The aim of our study was to evaluate the success, complications, and morbidity following a modified Thal fundoplication in children with reflux-associated respiratory disease (RARD) . We used a procedure consisting of retroesophageal hiatal plasty, wrapping the gastric fundus around the gastroesophageal junction 180 degrees, and fixation of the lesser curvature at the abdominal wall . Follow-up by questionnaire of 128 (77 male, 51 females) out of 196 antireflux procedures between 1992 and 1995 was achieved . Surgical therapy was considered justified whenever there was gastroesophageal reflux resulting in severe recurrent respiratory symptoms . Eleven percent of the children suffered from bronchiectasis . The diagnosis of RARD was based on a high index of suspicion, barium swallow with fluoroscopy, 24-hr two-level pH-monitoring, bronchoscopy, bronchoalveolar lavage and detection of lipid-laden alveolar macrophages, esophago-gastroscopy, and esophageal biopsy . Patients with bronchopulmonary diseases such as allergy, immunodeficiency, cystic fibrosis, primary ciliary dyskinesia, and malformation of the bronchial tree or vessels had been excluded . "Evident improvement" as a result of surgery was reported in 88%, "no change" in 10%, and a "change for the worse" in 2% of patients . Persistent mild difficulties in swallowing were observed in 11% . Paraesophageal hernia, gas-bloat syndrome, and dumping syndrome were not observed . Two children needed a second operation because of relapse . The use of emergency steroidal medication for acute respiratory distress decreased impressively (219 single doses/year before surgery vs . 30 single doses/year after surgery) . The need for more than 4 times/year of antibiotic therapy before surgery was reduced from 52 . 3% before to 14% after surgery . Most (90.6%) of the parents stated they would agree to have surgery done again if medically indicated . In conclusion, Thal fundoplication is sufficient, safe, and effective in the management of RARD . Complications of the procedure were minor and of little consequence to the patient . Support Care Cancer, 1999 Jul, 7(4), 284 - 6 Allergic reaction to the liposomal component of liposomal amphotericin B; Cesaro S et al.; A case of severe allergic reaction arising during treatment with Ambisome and unresponsive to antihistamine and steroid medication is reported . A 2.9-year-old female child with Hurler's syndrome received an allogeneic cord blood transplant from an unrelated donor . During the aplastic phase, liposomal amphotericin B (Ambisome) was administered as part of an empirical treatment for persistent fever . The patient developed an extensive maculopapular rash and severe itching that resolved only on discontinuation of the drug . The patient subsequently had interstitial pneumonia with ingravescent respiratory failure in spite of adequate antibiotic and antiviral treatment . Treatment with conventional amphotericin B was considered essential in this critically ill patient, and the conventional formulation was administered for 20 days without causing any reaction . Severe allergic reaction to Ambisome is a rare event but, taking into account that premedication or dose testing is not recommended for this formulation, careful monitoring of the patient being treated for the first time is warranted. Eur J Pharmacol, 1999 Jun 25, 374(3), 471 - 6 Endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway in the rat; Liao W et al.; Endotoxin has been recently shown to reduce plasma insulin-like growth factor I . As it was reported that histamine can induce gut-derived endotoxemia, we wanted to determine whether histamine has a similar effect on plasma insulin-like growth factor I . Compound 48/80 (a histamine releaser) was injected subcutaneously into rats, then blood was taken for plasma insulin-like growth factor I assay and the livers were assayed for insulin-like growth factor I mRNA . Like endotoxin, injection of compound 48/80 significantly reduced plasma insulin-like growth factor I . Six hours post-injection, plasma insulin-like growth factor I was reduced by 61% (P < 0.001), and 24 h post-injection, it was still lower (by 35% P < 0.001) than in the control group . Hepatic insulin-like growth factor I mRNA was not reduced by this treatment . The effect of compound 48/80 on plasma insulin-like growth factor I was significantly attenuated by oral administration of the histamine H1 receptor antagonist (chlorpheniramine), but not by the histamine H2 receptor antagonists (cimetidine and ranitidine) . Oral administration of polymyxin B (an antiendotoxin antibiotic) did not attenuate the effect of compound 48/80 on plasma insulin-like growth factor I at all . In conclusion, endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway . Our study suggests a novel role of histamine in the regulation of insulin-like growth factor I metabolism in vivo. Rev Med Interne, 1999 Jun, 20(6), 483 - 9 {Macrophagic myofasciitis: description and etiopathogenic hypotheses . Study and Research Group on Acquired and Dysimmunity-related Muscular Diseases (GERMMAD) of the French Association against Myopathies (AFM)}; Cherin P et al.; PURPOSE: A new type of inflammatory myopathy of unknown etiology has recently been described in France . The myopathy, called macrophagic myofasciitis, had never been described in the literature . METHODS: In December 1998, 35 cases of macrophagic myofasciitis were reported, showing an increase in its incidence since the description of the first case in 1993 . The first 22 cases are described . RESULTS: The 22 patients were each referred with a presumptive diagnosis of either polymyositis (11 patients), polymyalgia rheumatica (5 patients), mitochondrial cytopathy (4 patients), or congenital myopathy or muscle dystrophy (1 patient for each) . Clinical symptoms included myalgias (91%), arthralgias (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%) . Laboratory findings included elevated CK levels (50%) and a marked increased in the erythrocyte sedimentation rate (37%) . Electromyographic recordings showed the existence of myopathy (35%) . Muscle biopsy showed a unique pattern characterized by: (i) centripetal infiltration of the epimysium, perimysium and perifascicular endomysium by non epitheloid, cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-) with both large cytoplasm and PAS-positive content; (ii) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; (iii) occasional CD8+ T-cells; and, (iiii) minimal myocyte suffering . The disease symptoms were easily distinguishable from those of sarcoid myopathy and fasciitis-panniculitis syndromes . Infectious diseases known to be associated with reactive histiocytosis, including Whipple's disease, Mycobacterium avium intracellulare infection and malakoplakia, could not be documented . Patients' condition improved under corticosteroid therapy, associated or not with non-specific antibiotic therapy . CONCLUSION: A new inflammatory muscle disorder of unknown etiology, characterized by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France . Diagnosis is based on muscular biopsy . Numerous clinical, epidemiological and etiopathologic studies initiated by the GERMMAD (Groupe d'etudes et de recherche sur les maladies musculaires acquises) are in progress. Ann Dermatol Venereol, 1999 Apr, 126(4), 335 - 8 {Recurrence of erosive pustular scalp dermatosis after a skin graft}; Drouin CA et al.; INTRODUCTION: Erosive pustular dermatosis of the scalp is a rare and chronic dermatosis of unknown etiology with non specific histology and without effective treatment . It affects mostly old women . We have observed a 80 year-old male suffering from an erosive pustular dermatosis of the scalp following application of 5 p . 100 fluorouracile cream (Efudex) and his resistance to various treatments including skin graft . OBSERVATION: An 80 year-old man had been suffering, for many years from recurrent episodes of pustules, erosions and crusts of the scalp, following treatment with 5 p . 100 fluorouracile cream for skin lesions diagnosed as actinic keratosis . Different topical and systemic treatments were tried without much improvement . A skin graft of the scalp lesional area was finally done, showing a severe recurrence as a Koebner's reaction . Despite this recurrence, we have observed an easier control with a topical mixture of steroid and antibiotic . CONCLUSION: This recurrence of erosive pustular dermatosis of the scalp following skin graft had never been previously observed before, showing that removing affected skin did not control the disease, suggesting that anti-inflammatory agents probably originating from trauma persist. J Pathol, 1999 Jul, 188(3), 318 - 21 PCR analysis in the pathological diagnosis of Whipple's disease: emphasis on extraintestinal involvement or atypical morphological features; Gras E et al.; PCR analysis of species-specific bacterial 16S rRNA gene of Tropheryma whippelii was performed in biopsies from 10 cases of Whipple's disease (WD) . In seven patients showing the typical clinical picture of WD, PCR was performed on the diagnostic intestinal biopsy . In the remaining three cases (an autopsy case of disseminated WD and two patients showing lymphadenopathy as the initial clinical presentation), PCR was done on lymph node specimens . In one of the lymph node biopsies, an unusual sarcoidlike granulomatous reaction had led to the diagnosis of sarcoidosis . The specific bacterial DNA was detected in all cases, both in intestinal biopsies and in lymph node specimens . Follow-up biopsies after antibiotic therapy were evaluated in two patients . The two follow-up biopsies were negative, although in both of them scattered nests of PAS-positive macrophages remained . The results of this study suggest that PCR analysis of species-specific sequences of the 16S rRNA of Tropheryma whippelii is a very useful tool for the pathological diagnosis of WD . It confirms the diagnosis of WD in intestinal biopsies as well as in extraintestinal sites, even when the morphological appearance is not typical . It is also the most precise technique for monitoring therapeutic effects . Metabolism, 1999 Jul, 48(7), 922 - 7 The value of combined radionuclide and magnetic resonance imaging in the diagnosis and conservative management of minimal or localized osteomyelitis of the foot in diabetic patients; Vesco L et al.; Early diagnosis of osteomyelitis is helpful for a successful conservative treatment . The value of bone scanning combined with granulocytes labeled with hexamethylpropylene amine oxime (HMPAO) granulocyte-Tc99m (GN) radionuclide imaging (combined {RI}) with magnetic resonance imaging (MRI) for the diagnosis of osteomyelitis was assessed in 24 diabetic patients with foot ulcers . Evidence of osteomyelitis was based on the presence of at least one of the following criteria: (1) clinical bone involvement, (2) radiological bone involvement, (3) both positive combined RI and MRI, and (4) evidence of clinical bone involvement during the follow-up period . Thirteen patients had osteomyelitis . Seven patients had clinical bone involvement (sensitivity, 54%), five had radiological bone involvement (sensitivity, 38%), and 10 had positive combined RI for osteomyelitis (sensitivity, 77%) . MRI demonstrated a higher sensitivity (100%) . The specificity for combined RI and MRI was 82% . These results lead to a new diagnostic strategy for the early detection of minimal or localized osteomyelitis to avoid amputations . MRI is most appropriate following a negative x-ray in determining whether to treat osteomyelitis, since a negative MRI result rules out osteomyelitis . Antibiotic therapy should be used in the case of a positive MRI result, but Charcot joint disease can lead to false-positive MRI results . In this case, combined RI should be performed. Ann Thorac Surg, 1999 Jul, 68(1), 155 - 9 Repair of total anomalous pulmonary venous connection in infancy: experience from a developing country; Choudhary SK et al.; BACKGROUND: Corrective surgery for total anomalous pulmonary venous connection in infancy still carries high morbidity and mortality rates in developing countries . The present study evaluates the factors responsible for it . METHODS: Seventy-three infants were operated on for total anomalous pulmonary venous connection from January 1987 through October 1997 . Age ranged from 5 days to 12 months (mean, 3.9+/-0.24 months), with 10 (13.7%) patients younger than 1 month old . Patient weight varied from 2.0 to 5.2 kg (mean, 3.7+/-0.27 kg) . Most (90.5%) patients were small for their ages (< 50th percentile) . Anomalous connection was supracardiac in 42 (57.5%), cardiac in 18 (24.7%), infracardiac in 4 (5.5%), and mixed in 9 (12.3%) patients . Thirty-five patients had obstructed drainage . Preoperatively, 30 patients received antibiotic therapy for respiratory tract infection, 3 patients had balloon atrial septostomy, and 4 patients required mechanical ventilation . Fifteen patients (20.5%) were operated on as an emergency procedure . For supracardiac and infracardiac connections, a posterior approach was used for anastomosis . In cardiac type, coronary sinus was unroofed and the resultant defect along with atrial septal defect was closed with a single patch . RESULTS: The operative mortality rate was 23.3% (17 of 73) . Pulmonary hypertensive crisis was the cause of death in 10 patients . Emergency operation and weight less than the 25th percentile were the important risk factors for operative mortality . Young age (< 1 month) and type of drainage did not affect the mortality . Follow-up ranged from 1 to 108 months (mean, 56.4+/-26.0 months) . There were two late deaths . The actuarial survival (Kaplan Meier) at 9 years was 72.87%+/-5.39% . CONCLUSION: Failure of early recognition, and thus delayed referral, accounted for onset of cardiac cachexia, respiratory tract infection, and severe pulmonary hypertension, which had a major effect on unfavorable outcome. Acta Paediatr, 1999 Jun, 88(6), 631 - 5 Clinical symptoms and social factors in a cohort of children spontaneously clearing Helicobacter pylori infection; Tindberg Y et al.; In a cohort study of 305 Swedish children, repeated blood samples and structured questionnaires were obtained from 6 mo to 11 y of age . Of the 40 children seropositive for Helicobacter pylori in one or more samples, 32 (80%) had cleared the infection by 11 y of age . No association was found between H . pylori seropositivity at any time and reported antibiotic consumption, size of home and family, type of day-care, history of atopic disease, length of breastfeeding or peptic ulcer disease in the family . Girls reported more (p = 0.002) unspecified abdominal pain during childhood than boys, but the difference in H . pylori infection rate (15/150, 10% for boys and 25/144, 17% for girls) was not significantly different (p = 0.09) . Unspecified abdominal pain during childhood was reported more often (OR adjusted for gender = 2.2, 95% CI = 1.0-4.4, p = 0.04) for the children seropositive at some point (17/39, 44%) than for the seronegative children (54/217, 25%) . RAP at 11 y of age was more often reported by the 9/36 (25%) children seropositive at some time in life than by the 23/172 (13%) seronegatives, but the difference was not statistically significant (OR adjusted for gender = 2.0, 95% CI = 0.8-4.6, p = 0.1) . The study shows that H . pylori seropositivity was associated with a parental report of unspecified abdominal pain during childhood . Also, a history of unspecified abdominal pain was more common (OR = 51.6, 95% CI = 15.6-220, p < 0.001) in children reporting RAP at 11 y of age. Changgeng Yi Xue Za Zhi, 1999 Mar, 22(1), 147 - 52 Florid osseous dysplasia: case report; Kuo SB et al.; Florid osseous dysplasia (FOD) is a benign, non-neoplastic lesion characterized by multiple sclerosing masses only within the jawbones . It is most prevalent in middle-aged black women but uncommon in Orientals . Most cases are asymptomatic and should be left untreated . However, the jawbone involved in FOD is very susceptible to infection, including osteomyelitis developed from periodontitis, pulpopathosis, bone biopsy, wearing removable partial dentures, root canal therapy, tooth extraction, inappropriate dental treatment, etc . If secondary osteomyelitis develops, antibiotic and conservative dental therapy treatment is recommended for removing the sources of the odontogenic infection . Surgical removal of inflamed masses is indicated if the inflammatory signs and symptoms are persistent after antibiotic and conservative dental therapy . Here we report a rare FOD case in which an osteomyelitis resulting from generalized periodontitis and bone biopsy was triggered . The patient was accepted for surgery and follow-up in our department . The current literature of this disease is reviewed as well, focusing especially on the clinical manifestations, radiographic features, differential diagnosis, and treatment. Pediatr Surg Int, 1999 Jul, 15(5-6), 323 - 5 Conservative treatment of caustic esophageal injuries in children: 20 years of experience; Broto J et al.; The authors present their experience in the medical treatment of 1, 296 caustic esophageal injuries in children over the last 20 years in two study groups, one comprising the period up to 1989 and the other 1990 to 1996, comparing the different treatments used in each group . The treatment was based fundamentally on dilatations with anterograde mercury bougies, Savary bougies, or retrograde thread-guided bougies with gastrostomy . Pneumatic balloons or stenting procedures have also been employed in the last 3 years . Early fiberendoscopy was used systematically in the second group, which provides a more accurate evaluation of the esophageal lesions . Antibiotic coverage was done systematically during the first 10 days in all serious cases, while steroids were employed routinely only in the last 3 years . The results were similar in both groups, with a dilatation average of 32 in the first and 30 in the second group and an initial dilatation interval of 3 to 4 weeks in both . Using updated exploration and dilatation techniques, we drastically reduced the number of gastrostomies needed for retrograde thread-guided dilatations from 51 in the first group to 5 in the second, consequently improving the patients' life quality . There was no mortality and only five esophageal perforations, which did not require surgical treatment. Bone Marrow Transplant, 1999 Jun, 23(12), 1245 - 50 Optimal timing of G-CSF administration after CD34+ immunoselected peripheral blood progenitor cell transplantation; Piccirillo N et al.; G-CSF accelerates neutrophil recovery after autologous peripheral blood progenitor cell transplantation (aPBPCT), although the optimal timing for its administration is currently unknown . In order to establish the role and the optimal timing of administration of G-CSF after immunoselected CD34+ aPBPCT, we analyzed the data from 21 consecutive patients affected by haematological malignancies . Patients were randomized into three groups according to G-CSF administration after transplantation: day +1 (group B); day +7 (group C) or no G-CSF (group A) . Serum G-CSF level was evaluated until engraftment . The CD34+ cell dose reinfused was similar (P = 0.48) . G-CSF significantly reduced time to recovery of PMN >0.5 x 10(9)/l (11 vs 14 vs 20.5 days) (P= 0.00046); >1.0 x 10(9)/l (12 vs 15 vs 22) (P = 0.001) . No difference was observed in the number of days with PMN <0.1 x 10(9)/l (5.5 vs 7 vs 8 days) . Platelet count >50 x 10(9)/l and >100 x 10(9)/l, reticulocytes >1%, length of hospitalization, non-prophylactic antibiotic therapy, fever, incidence of sepsis and transfusion support did not differ . Early or delayed G-CSF after immunoselected CD34+ aPBPCT significantly accelerated PMN recovery but did not reduce the amount of supportive treatment or the duration of hospitalization . Delaying the initiation of G-CSF did not reduce the length of treatment (11.5 vs 12 days) . Early or delayed G-CSF administration resulted in G-CSF peak serum levels 7 (early)-12 (delayed)-fold greater than an endogenous response to neutropenia. Singapore Med J, 1999 Feb, 40(2), 101 - 3 Orbital cellulitis as a sole symptom of odontogenic infection; Ngeow WC; A case of periapical infection resulting in unilateral maxillary sinusitis and cellulitis of the ipsilateral lower eyelid is presented . The sole symptom was right orbital swelling . The possible pathway for the spread of this type of infection predisposing factors and possible complications are reviewed . The value of radiographic examination and antibiotic therapy are also discussed. Thorax, 1999 Aug, 54(8), 664 - 9 Relationship between early life respiratory illness, family size over time, and the development of asthma and hay fever: a seven year follow up study; Ponsonby AL et al.; BACKGROUND: The timing and mechanism of the inverse association between increasing sibling number and atopic disease are not yet understood . A study was undertaken to examine how family size at birth predicts early respiratory illness, to report the association between infant respiratory illness and childhood atopic disease, and to determine whether the protective effect of large family size operates during infancy or later childhood . METHODS: A prospective follow up study was carried out on 863 children (78%) of 1111 participants in the Tasmanian Infant Health Survey performed in 1988 . In 1988 household size and history of respiratory illness were obtained by parental interview at home (median age 35 days) and later by telephone (median age 85 days) . In 1995 asthma, hay fever, and household size were assessed by parental questionnaire in a large cross sectional survey . RESULTS: In 1988 increasing resident number (per resident) (adjusted odds ratio (AOR) 1.17 (95% CI 1.05 to 1.31)) and resident density (AOR 1.77 (95% CI 1.07 to 2.94)) were related to parental report of an upper respiratory tract infection (URTI) by one month of age . Children with a reported URTI by home interview were more likely to have subsequent asthma (adjusted relative risk (ARR) 1.27 (95% CI 1.05 to 1.53)) . The association between lower respiratory tract infection (LRTI) at telephone interview (relative risk (RR) 1.34 (95% CI 1.02 to 1.75) and asthma was reduced after adjustment for family history of asthma (ARR 1.27 (95% CI 0.98 to 1.66)) . Antibiotic use by home interview was not associated with subsequent asthma or hay fever . Indicators of family size in 1988 were associated with hay fever but not asthma but, in contrast, resident number in 1995 was inversely associated with asthma (AOR 0.82 (95% CI 0.72 to 0.92) per resident) and hay fever (AOR 0.82 (95% CI 0.71 to 0.96) per resident) . Children with no siblings were at risk for current asthma, particularly if symptoms began after the age of four (RR 2.81 (95% CI 1.36 to 5.84)) . CONCLUSIONS: The apparent protective effect of large household size and asthma could not be explained by an increase in reported early respiratory illness . The first year of life may not be the most critical time for the protective effect of large household size to be mediated in relation to asthma, but this effect occurred by the seventh year of life. Br J Ophthalmol, 1999 Aug, 83(8), 961 - 6 Effect of the cytostatic agent idarubicin on fibroblasts of the human Tenon's capsule compared with mitomycin C; Heilmann C et al.; BACKGROUND/AIMS: To investigate the in vitro effect of a short time exposure to the anthracycline idarubicin on proliferation, protein synthesis, and motility of human Tenon's capsule fibroblasts in comparison with the antitumour antibiotic mitomycin C . METHODS: After determination of effective concentrations of idarubicin, fibroblasts of the human Tenon's capsule were exposed to idarubicin or mitomycin C at concentrations ranging from 0.1 microg/ml to 1 microg/ml or from 2.5 microg/ml to 250 microg/ml, respectively, for 0.5, 2, or 5 minutes and cultured for 60 days . Cell death by apoptosis caused by idarubicin treatment was confirmed by Hoechst 33258 staining . Further proliferation was explored by cell counting and by (3)H-thymidine uptake . Protein synthesis was measured by (3)H-proline uptake and motility was assessed by agarose droplet motility assay . RESULTS: Idarubicin is able to exert toxicity and to induce apoptosis during a short time exposure of 0.5 minutes at concentrations of 0.3-1 microg/ml resulting in a significant reduction in cell number compared with the control after 60 days . For mitomycin C, higher concentrations and longer expositions were necessary . Even after treatment with 1 microg/ml idarubicin or 250 microg/ml mitomycin C a few cells were able to incorporate (3)H-thymidine . (3)H-proline uptake up to 10 days after exposure to 0.3 microg/ml idarubicin was found not to be decreased . Cell motility was reduced after treatment with 1 microg/ml idarubicin for 5 minutes or with 250 microg/ml mitomycin C for 2 or 5 minutes . For low mitomycin C concentrations, an increase in motility was found during the first 10 days . CONCLUSION: Idarubicin reduces proliferation of human Tenons's capsule fibroblasts after incubation for 0.5 minutes at concentrations as low as 0.3-1 microg/ml . In comparison, mitomycin C requires longer exposure times and higher doses for equal results . Therefore, idarubicin may be useful in the prevention of glaucoma filtering surgery failure. Biochemistry, 1999 Jul 13, 38(28), 8864 - 78 Substrate and inhibitor-induced conformational changes in the structurally related enzymes UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS); Krekel F et al.; UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) and 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS) have both a unique three-dimensional topology and overall reaction mechanism in common . In the case of MurA, the substrate-free, unliganded protein exhibits an "open" conformation . Upon binding of substrates, the protein forms a much more tightly packed so-called "closed" form following an induced fit mechanism . In this closed form, the substrates are properly positioned for catalysis . On the basis of the structural and mechanistic similarities of MurA and EPSPS, a similar conformational change is likely to occur in EPSPS to generate a catalytically competent active site . However, there is currently little experimental evidence available to support the occurrence of such a conformational change in EPSPS . Using limited tryptic digestion of MurA,(1) it could be shown that formation of the "closed" conformation of MurA is accompanied by a marked increase of stability toward proteolytic degradation . Formation of the closed conformation was achieved by addition of either an excess of both substrates or the sugar nucleotide substrate in conjunction with the antibiotic fosfomycin . Analysis of the MurA tryptic fragments by MALDI-TOF mass spectrometry demonstrates that the protection of the protein in either case is caused by (1) a specific shielding of regions thereby becoming less accessible as a result of the conformational change, and (2) an unspecific overall protection of the whole protein due to an apparently reduced flexibility of the peptide backbone in the binary and ternary complexes . The establishment of methods to describe the effects of tryptic digestion on MurA under various conditions was then extended to EPSPS . Although EPSPS was found to be much more stable toward proteolysis than MurA, the presence of shikimate 3-phosphate (S3P) and the inhibitor glyphosate led to a pronounced suppression of proteolytic degradation . When unliganded EPSPS was treated with trypsin, three of the peptide fragments obtained could be identified by mass spectrometry . Two of these are located in a region corresponding to the "catalytic" loop in MurA which participates in the conformational change . This indicates a conformational change in EPSPS, similar to the one observed in MurA, leading to the protection mentioned above . Corroborating evidence was obtained using a conformational sensitive monoclonal antibody against EPSPS which showed a 20-fold reduced affinity toward the protein complexed with S3P and glyphosate as compared to the unliganded enzyme. FEBS Lett, 1999 Jul 2, 454(1-2), 147 - 51 Cloning and expression of three cecropin cDNAs from a mosquito cell line; Sun D et al.; We have characterized full-length cDNAs encoding three isoforms of the antibiotic cecropin secreted by the C7-10 cell line from the mosquito, Aedes albopictus . The existence of two cecropin isoforms that differed from the previously described AalCecA was predicted by mass spectrometry and amino acid sequence analysis of peptides that eluted from reversed phase high performance liquid chromatography as a single peak just behind the previously described cecropin, AalCecA . Based on the amino acid sequence of the mature AalCecA peptide, we designed primers that amplified partial cDNAs encoding three different A . albopictus cecropins in reverse transcriptase polymerase chain reactions . Rapid amplification of cDNA ends was then used to complete the cDNA sequences of AalCecA, AalCecB and AalCecC, respectively . Each cDNA encoded a translation product containing a signal peptide, a pro region, and a mature cecropin peptide consistent with amino acid sequence data from chymotryptic digests . Although the mosquito cecropins shared 70-86% identity among each other, they shared only approximately 40% identity to cecropins from Drosophila melanogaster . Each of the cecropins was expressed within 2 to 4 h after induction, and transcripts measuring 0.3 to 0.5 kb continued to accumulate over 24 h . The three cecropins were secreted in roughly equimolar proportions, and 30 to 90% of AalCecB was amidated at the terminal glycine residue . In contrast, amidated forms of AalCecA and AalCecC constituted a smaller proportion of these isoforms. Chirurg, 1999 May, 70(5), 602 - 4 {Foreign body-induced thoracic actinomycosis as differential mediastinal space-occupying lesion diagnosis}; Moesta KT et al.; Thoracic actinomycosis is a rare disease often mistaken for malignancy . Untreated actinomycosis is associated with high mortality, the disease should, thus, be considered early . We report the case of a 58-year-old male patient who was referred to us for a suspected thoracic sarcoma . He had 6-month a history of hemoptysis, and there was severe deterioration in his general health . Only in a roundabout way was the diagnosis of thoracic actinomycosis established; it was caused by an aspirated chicken bone, as found by bronchoscopy . All symptoms rapidly regressed by antibiotic therapy and definitive healing was obtained . In the diagnostic work up of thoracic masses that may represent inflammatory diseases, lymphoma, thymus-associated, sarcomatous and germ-cell tumors, bronchoscopy is of primary diagnostic importance. Proc Natl Acad Sci U S A, 1999 Jul 20, 96(15), 8716 - 20 A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum; Mamoun CB et al.; Genomic information is rapidly accumulating for the human malaria pathogen, Plasmodium falciparum . Our ability to perform genetic manipulations to understand Plasmodium gene function is limited . Dihydrofolate reductase is the only selectable marker presently available for transfection of P . falciparum . Additional markers are needed for complementation and for expression of mutated forms of essential genes . We tested parasite sensitivity to different drugs for which selectable markers are available . Two of these drugs that were very effective as antiplasmodial inhibitors in culture, blasticidin and geneticin (G418), were selected for further study . The genes BSD, encoding blasticidin S deaminase of Aspergillus terreus, and NEO, encoding neomycin phosphotransferase II from transposon Tn 5, were expressed under the histidine-rich protein III (HRPIII) gene promoter and tested for their ability to confer resistance to blasticidin or G418, respectively . After transfection, blasticidin and G418-resistant parasites tested positive for plasmid replication and BSD or NEO expression . Cross-resistance assays indicate that these markers are independent . The plasmid copy number and the enzymatic activity depended directly on the concentration of the drug used for selection . These markers set the stage for new methods of functional analysis of the P . falciparum genome. Am J Obstet Gynecol, 1999 Jul, 181(1), 103 - 4 Severe immune hemolytic anemia associated with prophylactic use of cefotetan in obstetric and gynecologic procedures; Garratty G et al.; Second- and third-generation cephalosporins, especially cefotetan, are increasingly associated with severe, sometimes fatal immune hemolytic anemia . We noticed that 10 of our 35 cases of cefotetan-induced hemolytic anemias were in patients who had received cefotetan prophylactically for obstetric and gynecologic procedures . Eight of these cases of severe immune hemolytic anemia are described. Clin Exp Metastasis, 1999 Mar, 17(2), 119 - 24 Inhibitory effects of roxithromycin on tumor angiogenesis, growth and metastasis of mouse B16 melanoma cells; Yatsunami J et al.; We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis, tumor growth and metastasis of mouse B16BL6 melanoma cells . The inhibitory effect of roxithromycin on angiogenesis using mouse dorsal air sac model was dose-dependent, and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control . Administration of roxithromycin histologically reduced the development of microvessels and mononuclear cell infiltration . In vivo tumor growth studies demonstrated that intraperitoneal administration of roxithromycin at 20 mg/kg/day and 50 mg/kg/day reduced tumor size of B16BL6 melanoma to about 56% and 33% (experiment 1), 71% and 48% (experiment 2) of that in the respective controls . Roxithromycin also significantly inhibited pulmonary metastasis of B16BL6 cells in a spontaneous system . The inhibitory activities of roxithromycin on angiogenesis, tumor growth and metastasis were compared with those of a potent angiogenesis inhibitor, TNP-470 . These data demonstrated that roxithromycin has potent antiangiogenic and antitumor effects and might have possible therapeutic applications. Gan To Kagaku Ryoho, 1999 Jun, 26 Suppl 1, 191 - 8 {Malignant tumors in childhood}; Fujimoto T; With the consistent use of effective multimodal treatment, including combination chemotherapy, surgery and radiotherapy, the prognosis for all types of childhood cancer has dramatically improved over the last 25 years and the current 5-year survival rate is about 60-98% . Concurrently, developments in the laboratory have improved our understanding of the biology of childhood malignancies . The availability of new imaging techniques, particularly advances in magnetic resonance imaging, have enabled more accurate assessments of tumor extent and staging . Such imaging techniques are now routinely used in radiotherapy planning to maximize treatment to tumor sites, while minimizing the exposure of normal tissues . Progress in surgery has allowed for better reconstructive techniques to repair defects created by tumor resections . The availability of blood component transfusions and hematopoietic cytokines, and advances in supportive care such as isolation techniques and preventive high-dose antibiotic therapy for infections, have allowed for the administration of increasingly intensive chemotherapies . Advances in our understanding of hematopoietic stem cells have enabled for significant extension of the techniques of bone marrow transplantation . Many of the advances in diagnosis, treatment, and our understanding of the biology of childhood cancers have emerged from studies conducted at centers with the required expertise, where multidisciplinary teams are available to coordinate the diagnosis, treatment, supportive care, and follow-up of children with cancer . The increasing population of children who survive into adulthood has renewed concern for the long-term consequences of therapy . Current studies focus on "risk-adapted" therapy, where the most intensive treatment is reserved for patients at highest risk of treatment failure, whereas treatment of children with a more favorable prognosis is designed to minimize the acute and late toxicities of therapy. Wien Klin Wochenschr, 1999 May 7, 111(9), 368 - 70 Ceftriaxone associated hemolysis; Maraspin V et al.; A 48-year-old immunocompetent women treated with ceftriaxone 2 g daily i.v . for late Lyme borreliosis developed severe haemolytic anaemia . The patient had previously received the same antibiotic two times without any side effects . The first clinical signs began to appear on the seventh day of treatment . The patient developed severe anaemia with a haemoglobin level of 45 mg/l on day 10; thereafter she ceased to receive the antibiotic . The outcome was favourable . The clinical course and serologic results suggest that severe anaemia was induced by ceftriaxone and that drug adsorption as well as immune complex mechanisms were involved in the pathogenesis. Arch Otolaryngol Head Neck Surg, 1999 Jul, 125(7), 791 - 5 Pediatric angioedema: ten years' experience; Shah UK et al.; OBJECTIVE: To clarify the cause, clinical course, and management of children with angioedema . DESIGN: Retrospective review . SETTING: Urban tertiary care hospital for children . PATIENTS: Consecutive sample of all children hospitalized from January 1, 1987, to December 31, 1997, with the diagnosis of angioedema . Complete records permitting analysis were available for 10 patients . MAIN OUTCOME MEASURES: Sex, age, site, symptoms at initial examination, cause, therapeutic management, and clinical outcome . RESULTS: Seven boys and 3 girls, a mean age of 7.7 years, had angioedema of the head or neck, most often facial (8/10 {80%}) . Manifesting symptoms, in addition to swelling, were tenderness or pain in 4 children (40%), dyspnea in 3 (30%), dysphagia (including drooling and spitting) in 3 (30%), and hoarseness in 1 (10%) . Angioedema was due to food in 4 children (40%), insect bites in 3 (30%), infection in 2 (20%), and an antibiotic in 1 (10%) . Treatment was pharmacological in all cases . No child required intubation or tracheotomy . Care in the intensive care unit was necessary for 1 child (10%) . CONCLUSIONS: Pediatric angioedema exhibits a different cause and clinical manifestations than does adult angioedema . Prompt diagnosis and early treatment with an intravenous corticosteroid, an antihistamine, and/or epinephrine lead to rapid resolution and may, in appropriately staffed settings, avoid the need for care in the intensive care unit or airway intervention . Management algorithms based on adult experience must be modified to account for the milder pediatric manifestations of this immunologic disease. Am J Gastroenterol, 1999 Jul, 94(7), 1834 - 40 Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated; Ciociola AA et al.; OBJECTIVE: Published studies have estimated the rate of Helicobacter pylori (H . pylori) infection in patients with duodenal ulcer disease to be as high as 95%; the majority of remaining duodenal ulcers have been attributed to the use of ulcerogenic drugs such as nonsteroidal antiinflammatory drugs (NSAIDs) . We aimed to assess the H . pylori prevalence rates of U.S . duodenal ulcer patients in large, well-controlled studies . METHODS: More than 2900 patients with endoscopically diagnosed non-NSAID duodenal ulcers were enrolled in a series of six placebo-controlled, double-blind studies conducted in the United States that assessed H . pylori using a combination of tests . Patients were considered infected with H . pylori only if culture growth was observed, or both histological and CLOtest results were positive . Patients were considered uninfected if the results of at least two tests were negative . Patients with missing test results, results of only a single test, or conflicting test results were not evaluable for H . pylori assessment . RESULTS: Of the 2394 endoscopically diagnosed evaluable duodenal ulcer patients, 73% (1737) were confirmed infected with H . pylori at study entry . CONCLUSIONS: The results of six carefully designed and controlled studies suggest that an assumed H . pylori infection rate of approximately 95% may overestimate the actual rate of H . pylori infection in duodenal ulcer patients in the United States . Although H . pylori infection is an important factor in the etiology of noniatrogenic duodenal ulcer disease, other factors may predominate in some patients and should not be overlooked in determining an appropriate course of treatment . The empiric use of antibiotic therapy for ulcer patients without confirmation of the presence of H . pylori cannot be recommended. Am J Gastroenterol, 1999 Jul, 94(7), 1751 - 9 The influence of in vitro nitroimidazole resistance on the efficacy of nitroimidazole-containing anti-Helicobacter pylori regimens: a meta-analysis; van der Wouden EJ et al.; OBJECTIVE: The aim of this study was to determine the influence of nitroimidazole resistance (NIR) on the efficacy of treatment for Helicobacter pylori (H . pylori) infections by meta-analysis of the world literature . METHODS: A MEDLINE search, a manual search of all major gastroenterological journals from 1993 to 1997, and abstracts of gastroenterological and H . pylori meetings from 1993 to 1997 were performed . All treatment studies using a nitroimidazole and providing data about the medication used, dose frequency, total daily dose, duration of treatment, and eradication results in relation to NIR were included . Eradication had to be assessed by two biopsy-based tests or a urea breath test > or = 4 wk after treatment . Individual studies were pooled into groups according to the medication used and the duration of treatment . The pooled estimate of the odds ratio (OR) of NIR for treatment failure and its 95% confidence interval (95% CI) were calculated for each group using the logit method . To detect any possible bias, funnel plots (plots of effect estimates against sample size) were constructed . RESULTS: A total of 91 treatment arms, including a total of 4823 patients, were evaluated . The pooled ORs of NIR for treatment failure (95% CI) of proton pump inhibitors, bismuth, and quadruple regimens were 5.2 (3.8-7.1), 5.9 (4.1-8.3), and 7.0 (3.1-16.0), respectively . Eradication rates were 90% in susceptible strains but <75% in resistant strains . In susceptible strains, neither treatment duration nor the choice of the second antibiotic influenced efficacy . In resistant strains, tetracycline was more effective than amoxicillin (bismuth regimens), and the longer the duration of regimens (bismuth-amoxicillin regimens) the more effective they were . Only quadruple regimens given for > or = 1 wk were effective in resistant strains . CONCLUSIONS: NIR decreases treatment efficacy . Treatment duration and choice of other drugs influence the impact of NIR on treatment efficacy . If NIR is present, a nitroimidazole-containing regimen should be avoided or a quadruple regimen should be given for > 1 wk. Lab Anim Sci, 1999 Jun, 49(3), 248 - 53 Effect of respiratory tract disease on pharmacokinetics of tilmicosin in rats; Modric S et al.; BACKGROUND AND PURPOSE: In rats, murine respiratory mycoplasmosis is caused by Mycoplasma pulmonis . Tilmicosin, a macrolide antibiotic, has good tissue penetration and reaches high concentration in the lungs . Therefore, a model for studying the effects of disease on pharmacokinetics of tilmicosin was developed, using LEW rats . METHODS: Seventy-two LEW rats were assigned at random to two groups: one group was inoculated with M . pulmonis, and the other served as an uninoculated control group . On postinoculation day 31, all rats received a single dose of tilmicosin (20 mg/kg of body weight, subcutaneously) . RESULTS: Concentration of tilmicosin in the lungs of both groups of rats was significantly higher than serum tilmicosin concentration at all times . Infected rats had significantly higher lung tilmicosin concentration than did noninfected rats . No correlation was found between pH of the lungs and tilmicosin concentration in the lungs in either treatment group, nor did treatment have any effect on pH of the muscle . CONCLUSION: Tilmicosin accumulates in the lungs, and infection/inflammation further improves its tissue penetration. Am J Trop Med Hyg, 1999 Jun, 60(6), 899 - 903 Outbreak of histoplasmosis among cavers attending the National Speleological Society Annual Convention, Texas, 1994; Ashford DA et al.; In June 1994, 18 people developed serologically confirmed histoplasmosis following cave exploration associated with the annual National Speleological Society Convention in Bracketville, Texas . Six others had an undiagnosed illness suspected to be histoplasmosis . Two persons were hospitalized . We conducted a survey of convention attendees and a nested case-control study of those entering caves . We also conducted a histoplasmin skin test survey of a subgroup of the society, the Texas Cavers Association, who were attending a reunion in October 1994 . Among the national convention attendees, exposure to two caves was identified as responsible for 22 (92%) of the 24 cases; 12 (75%) of 16 people exploring one cave (Cave A) and 10 (77%) of 13 exploring a separate cave (Cave B) developed acute histoplasmosis . Additional risk-factors included fewer years of caving experience, longer time spent in the caves, and entering a confined crawl space in Cave A . Of 113 participants in the separate skin test survey, 68 (60%) were found to be skin test positive, indicating previous exposure to Histoplasma capsulatum . A positive skin test was significantly associated with male sex and more years of caving experience . Those less experienced in caving associations should be taught about histoplasmosis, and health care providers should pursue histories of cave exposure for patients with bronchitis or pneumonia that does not respond to initial antibiotic therapy. Int J Cancer, 1999 Jul 30, 82(3), 430 - 4 Apoptosis of medulloblastoma cells in vitro follows inhibition of farnesylation using manumycin A; Wang W et al.; Medulloblastoma is a malignant cerebellar tumor usually manifesting in childhood . We have previously shown that blocking the mevalonate pathway with lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibits medulloblastoma proliferation and induces apoptosis in vitro . The underlying mechanism may involve blocking post-translational modification of important mitogenic signal-transduction proteins . We show that p21 ras processing is blocked by lovastatin, suggesting that inhibition of isoprenylation may be important in lovastatin-induced apoptosis . To test this hypothesis, manumycin A, an antibiotic which inhibits farnesyl protein transferase and thus farnesylation, was administered to 4 medulloblastoma cell lines in vitro . We found that blocking protein farnesylation with manumycin A was followed by apoptosis in a time- and dose-dependent manner . However, cell death induced by manumycin A was uniformly more rapid and efficient, requiring only 12 to 24 hr of treatment, than lovastatin-induced apoptosis, which required 36 to 96 hr (depending on the cell line tested) . In addition, unlike lovastatin, which caused cell-cycle arrest in G1 phase and HMG-CoA reductase gene up-regulation, manumycin A had no effect on the cell cycle and resulted in down-regulation of HMG-CoA reductase gene expression . In both lovastatin- and manumycin A-treated cells, cellular cysteine protease precursor (CPP32) was activated, confirming the occurrence of apoptosis. J Pediatr Gastroenterol Nutr, 1999 Jul, 29(1), 42 - 5 Percutaneous endoscopic gastrostomy for continuous feeding in children with chronic cholestasis; Duche M et al.; BACKGROUND: Malnutrition associated with chronic cholestasis in children often requires continuous enteral feeding through a nasogastric tube, which may be poorly tolerated . METHOD: Percutaneous endoscopic gastrostomy was performed in five children (age range, 20 months to 13 years) with severe cholestasis (Alagille syndrome in four; biliary atresia in one) and severe malnutrition (mean weight, -2.6 standard deviations; mean height, -2.7 standard deviations) who were awaiting liver transplantation . The pull-through technique was used in patients under general anesthesia, and the button was set within 2 months . RESULTS: Minor wound infection required antibiotic therapy in one patient . In the four children with Alagille syndrome, enteral feeding by means of percutaneous endoscopic gastrostomy was used until liver transplantation for a mean period of 14 months with a mean weight gain of 350 g/mo and a mean height gain of 0.53 cm/mo . Seventeen months to 3 years, 3 months after liver transplantation, all four children were alive and in good clinical condition with normal readings in liver function tests . The technique had to be discontinued in the child with biliary atresia because of secondary occurrence of ascites, gastric intolerance, and refractory wound infection . CONCLUSION: Percutaneous endoscopic gastrostomy may be a valuable alternative to nasogastric tube for nutritional support in children with cholestasis and mild portal hypertension. Med Res Rev, 1999 Jul, 19(4), 307 - 19 Application of mass spectrometry for target identification and characterization; Loo JA et al.; Mass spectrometry-based methodologies span the vast expanse of drug discovery . Both electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) support proteomics-based research projects by identifying proteins separated and isolated by polyacrylamide gel electrophoresis . MALDI-MS-based surface scanning of one-dimensional isoelectric focusing gels, "virtual 2-D gel electrophoresis," represents a potentially high throughput means to map proteins and to determine protein profiles . Mass spectrometry can also be used to directly study the covalent and noncovalent interactions of drug molecules and biomolecule targets . Drug binding examples discussed include the binding of covalent and noncovalent inhibitors to src SH2 domain protein, and the interaction of aminoglycoside antibiotic neomycin and HIV Tat peptide-TAR RNA . Biopolymers, 1999 Sep, 50(3), 239 - 53 Orientation and immersion depth of a helical lipopeptaibol in membranes using TOAC as an ESR probe; Monaco V et al.; Trichogin GA IV is a lipopeptaibol antibiotic characterized by the sequence nOct-Aib1-Gly-Leu-Aib4-Gly-Gly-Leu-Aib8-Gly-Ile- Lol (nOct: n-octanoyl; Aib: alpha-aminoisobutyric acid; Lol, leucinol), which exhibits membrane-modifying properties . We synthesized step-by-step by solution methods three trichogin analogues, each with a single Aib --> 2,2,6,6-tetramethylpiperidin-1-oxyl-4-amino-4-carboxylic acid (TOAC) substitution . The similarity in the conformational propensities of the Calpha-tetrasubstituted alpha-amino acids Aib and TOAC allowed us to exploit these analogues to investigate the orientation and therefore the mechanism of action of trichogin in the membranes by the electron spin resonance (ESR) technique . A conformational analysis by Fourier transform ir absorption and CD in different organic solvents and in a membrane-mimetic environment indicated that the conformation of the natural lipopeptaibol remains almost unchanged in the three analogues . Moreover, for all of the analogues permeability measurements revealed membrane-modifying properties comparable to those of trichogin . Our ESR investigation demonstrated that, in liposomes based on phosphatidylcholine, trichogin lays parallel to the membrane surface with its hydrophobic face oriented toward the membrane interior . These results suggest that trichogin might modify membrane permeability via a carpet-like mechanism, at least in liposomes and in the absence of a transmembrane potential . Ned Tijdschr Geneeskd, 1999 Jun 12, 143(24), 1261 - 5 {Epidemic of respiratory tract infections by Mycoplasma pneumoniae in an institute for mentally disabled, investigated with polymerase chain reaction of a throat swab specimen}; Dorigo-Zetsma JW et al.; OBJECTIVE: To determine the spread of respiratory infection with Mycoplasma pneumoniae in an institute for mentally disabled persons . DESIGN: Descriptive . METHODS: In the period from mid-April to mid-September in a certain year the transmission of M . pneumoniae in the facility was evaluated using questionnaires and laboratory investigations . The laboratory investigations consisted of an M . pneumoniae specific polymerase chain reaction (PCR) on throat swab specimens and detection of antibodies in serum . RESULTS: 21 Residents and 26 staff members from 2/36 units were involved in the initial investigation . 17 Persons had complaints of a (recent) respiratory infection (cough, malaise and fever) . In 9 cases an M . pneumoniae infection was confirmed, in 5 cases by PCR and in 4 cases by serology . Two PCR positive persons had only complaints of coughing . During the investigation period 2 more persons were diagnosed with a respiratory infection due to M . pneumoniae . No new cases were found by investigation of contacts outside the facility . CONCLUSION: M . pneumoniae can cause an outbreak of M . pneumoniae respiratory infection in an institute for mentally disabled persons . Rapid detection of this pathogen is possible by PCR and is important for proper antibiotic therapy and epidemic-control measures. Rev Clin Esp, 1999 May, 199(5), 280 - 4 {Lung transplantation in cystic fibrosis . The results of the Clínica Puerta de Hierro (Madrid) and the Hospital La Fe (Valencia)}; Lazaro-Carrasco MT et al.; Retrospective analysis of cystic fibrosis patients who underwent pulmonary transplantation at Clinica Puerta de Hierro, Madrid, and at Hospital La Fe, Valencia . Since the beginning of the programme and until March 1998, a total of 63 patients with cystic fibrosis were studied . Among transplanted patients, 18 were males and 16 females, with a mean age of 18.9 years . All patients underwent sequential bilateral pulmonary transplantation . After transplantation, the most common complication was bacterial pneumonia which affected all patients . Six patients had dehiscence or stenosis of the bronchial suture . Other specific complications of this condition by frequency were intestinal obstruction and diabetes mellitus . Six patients developed obliterans bronchiolitis and one of them underwent a repeat transplantation . Three out of the 34 patients died, and the likelihood of survival after one and three years was 94% . Respiratory function tests and PaO2 peaked at sixth post-transplantation month . CONCLUSION: Pulmonary transplantation is a therapeutic option to be considered for the patient with cystic fibrosis and severe involvement of his/her pulmonary disease. J Mol Biol, 1999 Jul 16, 290(3), 699 - 716 Structure, dynamics and hydration of the nogalamycin-d(ATGCAT)2Complex determined by NMR and molecular dynamics simulations in solution; Williams HE et al.; The structure of the 1:1 nogalamycin:d(ATGCAT)2 complex has been determined in solution from high-resolution NMR data and restrained molecular dynamics (rMD) simulations using an explicit solvation model . The antibiotic intercalates at the 5'-TpG step with the nogalose lying along the minor groove towards the centre of the duplex . Many drug-DNA nuclear Overhauser enhancements (NOEs) in the minor groove are indicative of hydrophobic interactions over the TGCA sequence . Steric occlusion prevents a second nogalamycin molecule from binding at the symmetry-related 5'-CpA site, leading to the conclusion that the observed binding orientation in this complex is the preferred orientation free of the complication of end-effects (drug molecules occupy terminal intercalation sites in all X-ray structures) or steric interactions between drug molecules (other NMR structures have two drug molecules bound in close proximity), as previously suggested . Fluctuations in key structural parameters such as rise, helical twist, slide, shift, buckle and sugar pucker have been examined from an analysis of the final 500 ps of a 1 ns rMD simulation, and reveal that many sequence-dependent structural features previously identified by comparison of different X-ray structures lie within the range of dynamic fluctuations observed in the MD simulations . Water density calculations on MD simulation data reveal a time-averaged pattern of hydration in both the major and minor groove, in good agreement with the extensive hydration observed in two related X-ray structures in which nogalamycin is bound at terminal 5'-TpG sites . However, the pattern of hydration determined from the sign and magnitude of NOE and ROE cross-peaks to water identified in 2D NOESY and ROESY experiments identifies only a few "bound" water molecules with long residence times . These solvate the charged bicycloaminoglucose sugar ring, suggesting an important role for water molecules in mediating drug-DNA electrostatic interactions within the major groove . The high density of water molecules found in the minor groove in X-ray structures and MD simulations is found to be associated with only weakly bound solvent in solution . Int J Clin Pharmacol Ther, 1999 Jun, 37(6), 282 - 5 Average bioequivalence of two oral formulations of fluconazole in healthy subjects after multiple dosing; Atanasova I et al.; OBJECTIVES: To assess the average bioequivalence of two oral dosage forms of fluconazole--test (Fungolon, Antibiotic Co.) and reference (Diflucan, Pfizer)--in 18 healthy volunteers in a multiple dose-balanced, two-period, crossover study design . MATERIALS AND METHODS: The dosage regimen consisted of seven days treatment (first day 100 mg and 50 mg thereafter for six days given orally) and a washout period of two weeks between different treatments . Plasma samples were taken at regular time intervals according to the study protocol for measuring of plasma fluconazole concentrations . The primary and secondary parameters AUC(168-192), Cav, %PTF, Cmax, %Swing, %AUCF, 100 Cmax/AUC, T above Cav, and Tmax were estimated . RESULTS: The point estimates--geometric means of the ratios test (T)/reference (R) and the 90% confidence intervals (CI) for the ratios of expected medians (T)/(R), assuming a multiplicative model, estimated by parametric and nonparametric analysis--were in the defined ranges for accepting of bioequivalence for two of the primary metrics . The point estimates and the 90% CIs after parametric analysis of AUC(168-192) were 1.00 (0.98-1.02) and for the metric %PTF exceeded the accepted range for bioequivalence after parametric analysis the point estimate and 90% CI were 0.93 and (0.799-1.08) . CONCLUSION: The two preparations were considered to be bioequivalent in the rate and extent of absorption with significant variability across subjects. Actas Urol Esp, 1999 Apr, 23(4), 374 - 8 {Primary abscess of the psoas . Report of a case}; Conde Redondo C et al.; Psoas abscess is an uncommon condition at the present time . The initial anodyne signs and symptoms make diagnosis difficult . It can be diagnosed and rated as primary when the origin is not found, or secondary when a focus for infection spreading is detected . Drainage either percutaneously or by open surgery, and antibiotic therapy are the choice treatment, achieving an important survival rate . This paper presents a new case of psoas abscess, including a revision of the diagnosis and treatment of this condition. Actas Urol Esp, 1999 Apr, 23(4), 370 - 2 {Dissolution of ammonium-magnesium phosphate lithiasis with medical systemic treatment . Report of a case}; Tinajas Saldana A et al.; Presentation of one case of ammonium-magnesium phosphate calculi breakdown using systemic medical treatment with oral Acetohydroxamine acid dosed at 125 mg/8 h and antibiotic therapy based on the antibiogram results . This type of treatment is generally used in an attempt to eradicate the infection, and as prophylaxis of relapse following surgical treatment or SWEL in these difficult to eradicate calculi due to their high tendency to recur. Biochemistry, 1999 Jul 6, 38(27), 8605 - 11 The camptothecin-resistant topoisomerase I mutant F361S is cross-resistant to antitumor rebeccamycin derivatives . A model for topoisomerase I inhibition by indolocarbazoles; Bailly C et al.; DNA topoisomerase I is a major cellular target for antitumor indolocarbazole derivatives (IND) such as the antibiotic rebeccamycin and the synthetic analogue NB-506 which is undergoing phase I clinical trials . We have investigated the mechanism of topoisomerase I inhibition by a rebeccamycin analogue, R-3, using the wild-type human topoisomerase I and a well-characterized recombinant enzyme, F361S . The catalytic activity of this mutant remains fully intact, but the enzyme is resistant to inhibition by camptothecin (CPT) . Here we show that the mutated enzyme is cross-resistant to the rebeccamycin analogue . Despite their profound structural differences, CPT and R-3 interfere similarly with the activity of the wild-type and mutant topoisomerase I enzymes, and the drug-induced cleavable complexes are equally sensitive to the NaCl concentration . CPT and IND likely recognize identical structural elements of the topoisomerase I-DNA covalent complex; however, differences do exist in terms of sequence-specificity of topoisomerase I-mediated DNA cleavage . For the first time, a molecular model showing that CPT and IND share common steric and electronic features is proposed . The model helps to identify a specific pharmacophore for topoisomerase I inhibitors. J Vasc Interv Radiol, 1999 Jun, 10(6), 781 - 4 Air embolism during tunneled central catheter placement performed without general anesthesia in children: a potentially serious complication; Morello FP et al.; Central venous catheters have had an increasingly important role in a variety of patient care situations, including long-term antibiotic therapy, chemotherapy, and nutritional support . The recent past has seen a gradual transition from placement of vascular access catheters by surgeons to placement by interventional radiologists . The interventional radiology service places a majority of the vascular access devices at our children's hospital, including peripherally inserted central catheters, tunneled central venous catheters, temporary and permanent hemodialysis catheters, and subcutaneous ports . Most procedures performed by our interventional radiology service in children can be successfully completed with use of intravenous (i.v.) sedation, and a few require general anesthesia (GA) . Key advantages of GA over i.v . sedation include the ability to have positive pressure ventilation (PPV) or controlled apnea during the procedure . We report our experience of venous air embolism in three small children during placement of tunneled central venous catheters when GA was not used. J Vasc Interv Radiol, 1999 Jun, 10(6), 767 - 74 Incidence and management of catheter occlusion in implantable arm ports: results in 391 patients; Whigham CJ et al.; PURPOSE: To evaluate the incidence and management of catheter occlusion in implantable arm ports . MATERIALS AND METHODS: Findings were prospectively examined in 391 patients in whom 393 arm ports were placed . The indications for port placement included chemotherapy (n = 347), antibiotic administration (n = 35), combination chemotherapy/antibiotic use (n = 7), transfusion (n = 3), and phlebotomy (n = 1) . Of the total catheters, 323 (82.2%) underwent tip modification prior to placement . Malfunctioning catheters were usually treated with urokinase instillation . RESULTS: Three hundred ninety-three devices were implanted with 247 mean days of catheter use (total, 97,256 days; range, 1-694 days) . The overall incidence of catheter occlusion was 0.14 per 100 catheter days . A single catheter occlusion occurred in 90 (22.9%) catheters, with a mean of 90.1 days before the event . A second occlusion occurred in 36 (9.2%) of the above catheters, with a mean of 60.1 catheter days before the second event . Eighty-five (24.0%) of the 347 cancer patients had at least one occlusive event, yielding a complication rate of 0.098 per 100 catheter days at risk (95% confidence interval {CI}; 0.079-0.114) . Of the 35 patients receiving antibiotics, three (8.6%) had at least one occlusive event . This represented a complication rate of 0.032 per 100 catheter days at risk (95% CI; 0.010-0.061) . Seventeen (24.3%) of the nonmodified catheters developed an occlusion versus 72 (22.3%) of the modified (P > .05; Fisher exact test) . Of the catheters with a first occlusive event, 75 (98.7%) were treated successfully with urokinase instillation . Four (1.0%) patients developed symptomatic subclavian vein thrombosis . No bleeding complications occurred . CONCLUSION: Catheter occlusion is a common complication of long-term arm port placement, with a significantly higher incidence in the cancer patients in our series (P < . 05, Fisher exact test) . Catheter tip modification, however, does not considerably affect the incidence of occlusion . Low-dose urokinase therapy is a safe and efficacious treatment of catheter occlusion, obviating the need for catheter removal. Nucleic Acids Res, 1999 Jul 15, 27(14), 2931 - 7 Linkers designed to intercalate the double helix greatly facilitate DNA alkylation by triplex-forming oligonucleotides carrying a cyclopropapyrroloindole reactive moiety; Dempcy RO et al.; Triplex-forming oligonucleotides (TFOs) bind sequence-specifically in the major groove of double-stranded DNA . Cyclopropapyrroloindole (CPI), the electrophilic moiety that comprises the reactive subunit of the antibiotic CC-1065, gives hybridization-triggered alkylation at the N-3 position of adenines when bound in the minor groove of double-stranded DNA . In order to attain TFO-directed targeting of CPI, we designed and tested linkers to 'thread' DNA from the major groove-bound TFO to the minor groove binding site of CPI . Placement of an aromatic ring in the linker significantly enhanced the site-directed reaction, possibly due to a 'threading' mechanism where the aromatic ring is intercalated . All of the linkers containing aromatic rings provided efficient alkylation of the duplex target . The linker containing an acridine ring system, the strongest intercalator in the series, gave a small but clearly detectable amount of non-TFO-specific alkylation . An equivalent-length linker without an aromatic ring was very inefficient in DNA target alkylation. Am J Respir Crit Care Med, 1999 Jul, 160(1), 265 - 71 Maximizing the utilization of donor organs offered for lung transplantation; Gabbay E et al.; The number of patients awaiting lung transplantation (LT) and waiting time for surgery is increasing . In Australia, LT rates are 4 . 6/million population/yr, which despite low organ donation rates, are the highest published in the world . The Australian organ allocation system allows identification of marginal donors and therapeutic manipulation where appropriate . This study aims to assess the impact of utilization of marginal donors and aggressive donor management . A comparison between published donor criteria and local practice is made, allowing assessment of the effect of using marginal donors on outcome . Donor management included antibiotic therapy, strict fluid management, physiotherapy, bronchoscopy and bronchial toilet, and alteration of ventilatory settings including initiation of pressure support . Blood gases were repeated to assess the results of interventions . Between January 1, 1995 and May 31, 1998, we performed 140 transplants from 112 of 219 (51%) lung donor offers . Of these donors, 48 (43%) satisfied all published criteria for suitable donor organs (Group 1 = ideal donors) and 64 (57%) did not (Group 2 = marginal donors) . Criteria breached by the marginal donors were: an initial ratio of arterial oxygen pressure to fraction of inspired oxygen (PaO2/FIO2) < 300 mm Hg (n = 20), abnormal radiology (n = 39), pulmonary infection (n = 24), 20 pack-years smoking (n = 5) and age > 55 yr (n = 4) . Therapeutic manipulation resulted in improvement in the PaO2/FIO2 ratio in 20 donors (Group 3) who would not otherwise have been used . Immediate and 24 h postoperative gas exchange and length of intensive care unit (ICU) stay was not different for recipients from donors from all three groups . Overall survival was 94% at 30 d, 83% at 1 yr, 70% at 2 yr, and 62% at 3 yr and was not significantly different from the three groups . We conclude that organ utilization can be maximized by therapeutic manipulation and utilization of marginal donors without compromising results from transplantation. Science, 1999 Jul 2, 285(5424), 110 - 3 Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line; Lohmann V et al.; An estimated 170 million persons worldwide are infected with hepatitis C virus (HCV), a major cause of chronic liver disease . Despite increasing knowledge of genome structure and individual viral proteins, studies on virus replication and pathogenesis have been hampered by the lack of reliable and efficient cell culture systems . A full-length consensus genome was cloned from viral RNA isolated from an infected human liver and used to construct subgenomic selectable replicons . Upon transfection into a human hepatoma cell line, these RNAs were found to replicate to high levels, permitting metabolic radiolabeling of viral RNA and proteins . This work defines the structure of HCV replicons functional in cell culture and provides the basis for a long-sought cellular system that should allow detailed molecular studies of HCV and the development of antiviral drugs. Obstet Gynecol, 1999 Jul, 94(1), 112 - 6 Modern obstetric management and outcome of infants with gastroschisis; Rinehart BK et al.; OBJECTIVE: To determine whether outcomes of infants with gastroschisis differed by mode or site of delivery, diagnostic method, or when maternal-fetal medicine consultation was given . METHODS: Charts of 32 infants born at the University of Mississippi Medical Center or admitted to the neonatal intensive care unit between September 1992 and June 1998 were reviewed for maternal demographic characteristics and neonatal outcomes . Statistical analysis was done using Student t test, analysis of variance, chi2, and Kruskal-Wallis test with P<.05 considered statistically significant . RESULTS: There were no statistically significant differences in neonatal outcomes by method or site of delivery, diagnostic method, or maternal-fetal medicine consultation before delivery . Infants delivered vaginally had higher Apgar scores at 1 and 5 minutes (9 versus 7 and 9 versus 8, respectively, P<.05) . Vaginally delivered infants required more days of antibiotic therapy than those delivered abdominally (10 versus 3 days, P<.05) but had a shorter interval to enteral feedings (15 versus 30 days, P<.05) . CONCLUSION: Outcomes of infants with isolated gastroschisis were not significantly affected by method or site of delivery, diagnostic method, or maternal-fetal surveillance . Although the findings of this investigation were largely negative and the statistical power limited due to the rarity of this fetal disruption, small series of cases of gastroschisis need to be analyzed to resolve current controversies surrounding optimal treatment of gastroschisis. Antimicrob Agents Chemother, 1999 Jul, 43(7), 1565 - 73 Identification and analysis of the balhimycin biosynthetic gene cluster and its use for manipulating glycopeptide biosynthesis in Amycolatopsis mediterranei DSM5908; Pelzer S et al.; Seven complete genes and one incomplete gene for the biosynthesis of the glycopeptide antibiotic balhimycin were isolated from the producer, Amycolatopsis mediterranei DSM5908, by a reverse-cloning approach and characterized . Using oligonucleotides derived from glycosyltransferase sequences, a 900-bp glycosyltransferase gene fragment was amplified and used to identify a DNA fragment of 9,882 bp . Of the identified open reading frames, three (oxyA to -C) showed significant sequence similarities to cytochrome P450 monooxygenases and one (bhaA) showed similarities to halogenase, and the genes bgtfA to -C showed similarities to glycosyltransferases . Glycopeptide biosynthetic mutants were created by gene inactivation experiments eliminating oxygenase and glycosyltransferase functions . Inactivation of the oxygenase gene(s) resulted in a balhimycin mutant (SP1-1) which was not able to synthesize an antibiotically active compound . Structural analysis by high-performance liquid chromatography-mass spectrometry, fragmentation studies, and amino acid analysis demonstrated that these oxygenases are involved in the coupling of the aromatic side chains of the unusual heptapeptide . Mutant strain HD1, created by inactivation of the glycosyltransferase gene bgtfB, produced at least four different compounds which were not glycosylated but still antibiotically active. Obstet Gynecol, 1999 Jul, 94(1), 120 - 3 Neonatal morbidity at 34-37 weeks: the role of ruptured membranes; Steinfeld JD et al.; OBJECTIVE: Evaluate neonatal morbidity in deliveries occurring between 34 0/7 and 36 6/7 weeks' gestation, comparing outcomes in pregnancies complicated by preterm premature rupture of membranes with those in which delivery occurred with intact membranes prior to the onset of labor . METHODS: The obstetric database was reviewed for a 5-year period . Healthy gravidas delivering nonanomalous singleton gestations from vertex presentations were evaluated, with corticosteroid or antibiotic administration or both noted . The neonatal database was reviewed for the following complications: admission to the neonatal intensive care unit, need for assisted ventilation, and development of hyaline membrane disease, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, or culture-proven sepsis . Groups were compared using chi2 tests . The power of this study to detect a ten-fold decrease in the likelihood of neonatal complications at the P<.05 significance level was greater than 90% . RESULTS: Of 853 eligible pregnancies, 414 (48.5%) gravidas had ruptured membranes prior to the onset of active labor . No difference existed between groups in the number of patients who had received corticosteroids during pregnancy, but patients with ruptured membranes were more likely to have received antibiotics prior to delivery . No neonatal deaths occurred, and neonatal morbidity was low in both groups . CONCLUSION: No clinically significant difference exists in neonatal outcome between 34 0/7 and 36 6/7 weeks' gestation as the result of membrane status prior to the onset of labor. Minerva Anestesiol, 1999 May, 65(5 Suppl 1), 86 - 91 {Inhalation of foreign bodies}; Pigna A et al.; Accidental aspiration of a foreign body (FB) is an event which is reasonably frequent and dramatic in children and is still today one of the main causes of death due to accidents at home in children up to three-four years of age . The severity of the clinical picture varies according to the size, shape, type and site of arrest of the material aspirated and can be associated with both severe asphyxial forms and forms with insidious and vague symptoms which are difficult to diagnose correctly . A late diagnosis is however a fairly common event in literature . An anamnesis suggesting probable aspiration in a child under the age of 3 should direct doctors towards diagnostic and operative endoscope examinations of the patient, even where there is a negative clinical and radiological picture . Organic material, mainly peanuts, represented 60-75% of the findings, particularly in the 0-3 year age-band . In the other of cases inorganic material was extracted from school-age children . Aspiration of a FB exposes the patient to risk of serious complications and sequelae . Antibiotic, dexamethasone therapy and the ventilation support in the CPAP helped to avoid post-extractive sequelae . Prevention should in any case be the primary aim as regards to aspiration of foreign bodies in children . This should be stimulated by appropriate educational campaigns to raise awareness . The study included 62 child patients observed in the Department of Anesthesia and Intensive Care of the S.Orsola-Malpighi Hospital of Bologna over the last 11 years who were admitted for suspected FB aspiration. Zhonghua Yi Xue Za Zhi (Taipei), 1999 Jun, 62(6), 341 - 9 Computerized tomography-guided stereotactic aspiration of brain abscesses: experience with 28 cases; Hsieh PC et al.; BACKGROUND: Computerized tomography (CT)-guided stereotactic techniques allow accurate identification of brain abscesses and provide promising results for the management of brain abscesses . METHODS: We reviewed the results of stereotactic aspiration of brain abscesses in 28 consecutive patients from 1984 to 1995 . In all patients, the diagnosis of brain abscess was made by computerized tomography (CT) . All patients underwent stereotactic aspiration of abscesses as the primary surgical therapy . Intravenous antibiotics were administered preoperatively and adjusted according to organism type and sensitivity to antibiotics . In patients with multiple lesions, aspirations were performed on abscesses larger than 2 cm in diameter or on those causing significant mass effects . CT was performed weekly to monitor abscess growth or failure to resolve . Patients were followed on an outpatient basis . This report is a retrospective review of clinical features, diagnostic methods, treatment and postoperative results . RESULTS: A total of 19 patients had good recoveries and six patients had mild neurologic sequelae . One patient had persistent conscious impairment . Intracranial hemorrhage occurred in one patient . Two deaths occurred during hospitalization . One patient with a fungal infection underwent additional surgical excision of the abscess . Most patients had resolution of abscesses after stereotactic treatment within two months . The cure rate was 92% in patients with bacterial brain abscesses treated with stereotactic aspiration and intravenous antibiotics for six weeks . CONCLUSIONS: Stereotactic surgery is a procedure with minimal morbidity and mortality, and can be the treatment of choice for brain abscesses when combined with appropriate antibiotic therapy. Lakartidningen, 1999 May 26, 96(21), 2591 - 5 {Dyspepsia--can we follow dogmatic guidelines in a nuanced reality? Individual management of patients with dyspepsia with risk of stomach ulcer}; Agreus L et al.; A review of subject literature suggests management strategies for the treatment of dyspepsia to be characterised by marked differences . In some strategies the possibility of indirect Helicobacter pylori testing (e g, breath tests) is ignored and endoscopy recommended as the only appropriate investigation; only those with verified disease are treated, and the risk of antibiotic overuse is minimised . In other strategies, indirect H pylori testing is recommended for younger patients (< 45 years of age) without alarming symptoms, either to select patients for endoscopy or to eradicate the infection (i.e., irrespective of whether the patient has peptic ulcer disease or not, on the grounds that the risk of having or developing such disease is thus minimised . The article consists in discussion of the different strategies, and suggests a choice of investigations tailored to the needs of the individual patient to be preferable to dogmatic adoption of either approach, though endoscopy should be available without delay if required . Moreover, the accuracy of the various indirect H pylori tests needs to be considered . To be acceptable for use in primary care, it is suggested that recommendations regarding interventions for the various disorders associated with dyspepsia should be characterised by reasonably comparable risk levels . An algorithm with alternative strategies suited to available facilities and the patient's needs and wishes is also presented. Liver Transpl Surg, 1999 Jul, 5(4), 275 - 81 Endoscopic stenting of the gallbladder for symptomatic gallbladder disease in patients with end-stage liver disease awaiting orthotopic liver transplantation; Shrestha R et al.; Cholecystectomy in patients with advanced cirrhosis is associated with excessive morbidity and mortality . Because open cholecystectomy in patients with Child's class C cirrhosis has a reported mortality rate as high as 83%, symptomatic gallbladder disease in patients awaiting orthotopic liver transplantation (OLT) poses a unique clinical problem . The goal of this study is to determine whether the treatment of symptomatic gallbladder disease with endoscopic stenting of the gallbladder effectively reduces biliary symptoms and complications or the need for cholecystectomy . Thirteen patients with symptomatic gallbladder disease with and without cholelithiasis and advanced cirrhosis who were candidates for OLT underwent placement of a biliary stent from the gallbladder to the duodenum at endoscopic retrograde cholangiography . In each patient, biliary symptoms and complications ceased after stent placement . Seven patients underwent successful OLT 1 to 24 months after the procedure . One patient subsequently became a noncandidate for OLT and died of diabetes complications 3 years after the procedure . Five others are awaiting OLT (6 to 28 months postprocedure) . One patient had recurrent pericholecystic fluid collection requiring percutaneous drainage and antibiotic therapy 8 months after the procedure . No patient has had recurrent symptoms, and currently all patients are free of complications . None required surgical intervention of the gallbladder or biliary tree . We conclude that endoscopic stenting of the gallbladder is the preferred treatment for symptomatic gallbladder disease in patients with end-stage liver disease awaiting OLT . This approach is noninvasive, safe, and effective in preventing potential morbidity and mortality. Curr Opin Ophthalmol, 1998 Aug, 9(4), 45 - 9 Current diagnosis and treatment of corneal ulcers; Benson WH et al.; Successful treatment for a corneal ulcer requires proper diagnosis and antibiotic selection . The management should be guided by the severity of the clinical presentation, the ophthalmologist's confidence in making the proper diagnosis of bacterial keratitis, and the level of trust in the antibiotic agents chosen for the causative organisms . Universal standards include pretreatment cultures and dual broad-spectrum fortified antibiotics . Recent changes in practice suggest that empirical monotherapy treatment with a fluoroquinolone antibiotic may be appropriate for certain cases of bacterial keratitis . This article reviews the various diagnostic methods and treatment options currently practiced in the ophthalmic community. J Dairy Sci, 1999 Jun, 82(6), 1202 - 12 Intracellular accumulation, subcellular distribution, and efflux of tilmicosin in bovine mammary, blood, and lung cells; Scorneaux B et al.; Tilmicosin is a semisynthetic macrolide antibiotic currently approved for veterinary use in cattle and swine to combat respiratory disease . Because the concentrations of tilmicosin are generally low in bovine serum, the interaction of tilmicosin with three types of bovine phagocytes (monocyte-macrophages, macrophages, and neutrophils from blood, lungs, and mammary gland, respectively) and mammary gland epithelial cells was evaluated to provide an understanding of potential clinical efficacy . After incubation with radiolabeled tilmicosin, uptake was determined and expressed as the ratio of the intracellular to the extracellular drug concentration . Accumulation of tilmicosin at 4 h of incubation by the alveolar macrophages (Cc/Ce 193) was 4 to 13 times more than that observed in monocyte-macrophages (Cc/Ce 43), neutrophils, (Cc/Ce 13), or mammary epithelial cells (Cc/Ce 20) . Subcellular distribution showed that 70 to 80% of tilmicosin was localized in the lysosomes . Uptake in mammary gland cells was dependent on cell viability, temperature, and pH, but was not influenced by metabolic inhibitors or anaerobiosis . However, lipopolysaccharide exposure increased tilmicosin uptake by the bovine mammary macrophages and epithelial cells . When neutrophils and epithelial cells were incubated in the presence of tilmicosin and extracellular tilmicosin was then removed, 40% of the intracellular tilmicosin remained cell associated after 4 h of incubation (i.e., 60% effluxed), but only 25% remained in macrophages . These in vitro interactions of tilmicosin with bovine phagocytes and epithelial cells suggest an integral role in effecting clinical efficacy. Br J Pharmacol, 1999 May, 127(2), 498 - 504 Tacrolimus suppresses tumour necrosis factor-alpha and protects against splanchnic artery occlusion shock; Squadrito F et al.; 1 . Tumour necrosis factor (TNF-alpha) is a pleiotropic cytokine which is deeply involved in the pathogenesis of splanchnic artery occlusion (SAO) shock . Tacrolimus, formerly known as FK506, is a macrolide antibiotic, that blocks the transcription of several proinflammatory cytokines including TNF-alpha . 2 . Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45 min . This surgical procedure resulted in an irreversible state of shock (SAO shock) . Sham operated animals were used as controls . SAO shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham shocked rats survived more than 4 h), enhanced serum TNF-alpha concentrations (415+/-12 U ml(-1)), decreased mean arterial blood pressure (MAP), leukopenia and increased ileal leukocyte accumulation studied by means of myeloperoxidase activity (MPO=7.5+/-0.3 U g(-1) tissue) . Moreover aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1 nM - 10 microM), reduced responsiveness to acetylcholine (ACh, 10 nM - 10 microM) and increased staining for intercellular adhesion molecule-1 (ICAM-1) . Furthermore increased mRNA for TNF-alpha was observed in peritoneal macrophages of SAO shocked rats . 3 . Tacrolimus (100 microg kg(-1), 5 min after splanchnic arteries occlusion) increased survival rate (SAO + Tacrolimus = 100% at 4 h of reperfusion), reverted the marked hypotension, reduced serum TNF-alpha (15+/-3 U ml(-1)), ameliorated leukopenia, reduced ileal MPO (0.9+/-0.01 U g(-1) tissue), restored to control values the hyporeactivity to PE . improved the reduced responsiveness to ACh and blunted the enhanced immunostaining for ICAM-1 in the aorta . Finally tacrolimus suppressed cytokine mRNA levels in peritoneal macrophages . 4 . The data suggest that tacrolimus may represent a new therapeutic approach in circulatory shock. Skeletal Radiol, 1999 Apr, 28(4), 224 - 8 Hypertrophic osteoarthropathy of one leg--a sign of aortic graft infection; Spruijt S et al.; We report a rare case of hypertrophic osteoarthropathy (HOA) confined to the right leg secondary to aortic graft infection . The development of HOA exclusively localized to areas distal to a vascular prosthesis may be the presenting manifestation of graft infection and a crucial diagnostic clue in the early detection of vascular graft infection . HOA is diagnosed by its characteristic radiographic and scintigraphic pattern . Most prosthetic, especially aortic, graft infections are uniformly fatal if not treated by aggressive surgical and antibiotic therapy . Recognition of this uncommon association may facilitate an early diagnosis, which usually requires immediate surgical therapy. J Foot Ankle Surg, 1999 May-Jun, 38(3), 203 - 7 The crescentic first metatarsal basilar osteotomy for correction of metatarsus primus varus; Fox IM et al.; The crescentic basilar first metatarsal osteotomy has been largely abandoned by the podiatric community in recent years in favor of proximal wedge-type osteotomies for the correction of metatarsus primus varus with large intermetatarsal angles . In most cases, this was due to the inherent instability of the osteotomy and difficulties with fixation . However, the crescentic osteotomy has the ability to correct in all three planes with less shortening than the wedge-type osteotomies . New fixation techniques, such as the small cannulated screw systems, have allowed for les