Antibiotics

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 less technical difficulty in obtaining rigid internal fixation . In this article, the authors describe the results in 29 feet (27 patients) where the crescentic osteotomy was performed along with a metatarsaphalangeal joint procedure ranging from a McBride (with or without lateral sesamoidectomy) to a phalangeal osteotomy . Preoperative intermetatarsal angles ranged from 11 degrees to 22 degrees, with an average of 18.6 degrees . Postoperative intermetatarsal angles ranged from 2.6 degrees to 8.2 degrees with an average of 5.1 degrees . The preoperative hallux abductovalgus angles ranged from 25 degrees to 38 degrees, with an average of 33.6 degrees . The postoperative hallux abductovalgus angles ranged from 4 degrees to 18 degrees with an average of 11 degrees . Complications included one hallux varus, one delayed union, and three cases of superficial cellulitis that resolved with oral antibiotic therapy.

J Foot Ankle Surg, 1999 May-Jun, 38(3), 194 - 202
Subtotal calcanectomy for the treatment of large heel ulceration and calcaneal osteomyelitis in the diabetic patient; Baravarian B et al.; Diabetic, neuropathic patients are often at risk for ulceration . Those that are temporarily or permanently limited in ambulation and restricted to a supine position are over time very susceptible to heel decubiti . Twelve patients with heel ulceration and calcaneal osteomyelitis who underwent subtotal calcanectomy are presented . Aggressive debridement of all nonviable tissue was coupled with a thorough antibiotic course in all cases . Ten of the 12 were completely healed at follow-up of 13 months . Two patients died of cardiac complications unrelated to their surgery . Postoperatively, the 10 patients were placed in an ankle-foot orthosis combined with a custom-molded shoe . All patients who were ambulatory preoperatively were able to resume their function after surgery . Subtotal calcanectomy is a relatively simple procedure to perform . In the presence of adequate vasculature, it is a good alternative to below-the-knee amputation and the accompanying sequelae.

Cancer Res, 1999 Jun 15, 59(12), 2931 - 8
KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules; Soga S et al.; Radicicol, a macrocyclic antifungal antibiotic, has been shown to bind to the heat shock protein 90 (Hsp90) chaperone, interfering with its function . Hsp90 family chaperones have been shown to associate with several signaling molecules and play an essential role in signal transduction, which is important for tumor cell growth . Because radicicol lacks antitumor activity in vivo in experimental animal models, we examined the antitumor activity of a novel radicicol oxime derivative, radicicol 6-oxime (KF25706), on human tumor cell growth both in vitro and in vivo . KF25706 showed potent antiproliferative activities against various human tumor cell lines in vitro and inhibited v-src- and K-ras-activated signaling as well as radicicol . In addition, Hsp90 family chaperone-associated proteins, such as p185erbB2, Raf-1, cyclin-dependent kinase 4, and mutant p53, were depleted by KF25706 at a dose comparable to that required for antiproliferative activity . KF25706 was also shown to compete with geldanamycin for binding to Hsp90 . KF29163, which is an inactive derivative of radicicol, was less potent both in p185erbB2 depletion and Hsp90 binding . More importantly, KF25706 showed significant growth-inhibitory activity against human breast carcinoma MX-1 cells transplanted into nude mice at a dose of 100 mg/kg twice daily for five consecutive i.v . injections . KF25706 was also shown to possess antitumor activity against human breast carcinoma MCF-7, colon carcinoma DLD-1, and vulval carcinoma A431 cell lines in vivo in an animal model . Finally, we confirmed the depletion of Hsp90-associated signaling molecules (Raf-1 and cyclin-dependent kinase 4) with ex vivo Western blotting analysis using MX-1 xenografts . In agreement with in vivo antitumor activity, KF25706 depleted Hsp90-associated molecules in vivo, whereas KF29163 and radicicol did not show this activity in vivo . Taken together, these results suggest that antitumor activity of KF25706 may be mediated, at least in part, by binding to Hsp90 family proteins and destabilization of Hsp90-associated signaling molecules.

Ann Plast Surg, 1999 Jun, 42(6), 665 - 72
Evaluation of results and treatment variables for pressure ulcers in 48 veteran spinal cord-injured patients; Goodman CM et al.; This retrospective study of 48 spinal cord-injured patients with pressure ulcers seen at a tertiary referral Veterans Hospital spinal cord injury unit between 1992 and 1997 correlates a number of variables (co-morbid conditions, nutritional status, smoking history, type of repair performed, type of bed used postoperatively, ulcer location and severity, duration of postoperative antibiotic therapy, time elapsed before sitting rehabilitation began, and length of hospital stay) with ulcer repair outcome measures, including postoperative systemic and wound-healing complications, recurrence rates, and the development of new ulcers at different sites . Surgical complication rates were high, occurring in 19 patients (39.6%), and ulcer recurrence or new ulcer development occurred in 38 patients (79.2%) . Correlations were found between ulcer location and postoperative wound separation and the length of hospitalization . The hospital course was shorter if the ulcer was new rather than recurrent . Other than the finding that chronic smokers had longer courses of antibiotic therapy, smoking did not correlate statistically with other outcome variables, including wound-healing complications . No significant correlations were found between any postoperative systemic or wound complications, ulcer recurrence, or new ulcer development and patient age, level of spinal cord injury, number of ulcers and grade, laboratory values, mental status, cardiac or pulmonary disease, diabetes, and presence or absence of osteomyelitis.

Helicobacter, 1999 Jun, 4(2), 69 - 76
Helicobacter pylori and gastric cancer: what are the benefits of screening only for the CagA phenotype of H . pylori?
Harris RA, Owens DK, Witherell H, Parsonnet J.
BACKGROUND: Strains of Helicobacter pylori that express the CagA protein are associated with a threefold increased gastric cancer risk as compared to H . pylori strains that do not express CagA . Screening and treatment only for CagA antibodies should target those individuals at highest gastric cancer risk while reducing the number of patients requiring antibiotics . We compared the costs and benefits of screening asymptomatic 50-year-old individuals for CagA, screening for all H . pylori strains, and no screening, both in the United States and abroad . MATERIALS AND METHODS: We employed Markov cost-effectiveness analysis using data from randomized, case-control, and cohort studies . RESULTS: In the United States, CagA screening would result in 1.5 million fewer antibiotic treatments but would prevent 1,400 fewer gastric cancers than would screening for all H . pylori . The incremental cost-effectiveness of CagA screening is $23,900 per life-year gained; for H . pylori screening, it is $25,100 . Screening in countries with epidemiological characteristics similar to those of Colombia, Finland, and Japan costs less than $5,000 per life-year gained, and the difference between CagA and H . pylori screening is smaller than that in the United States . CONCLUSIONS: Screening only for CagA-positive H . pylori is not substantially better than is screening for all H . pylori, either in the United States nor abroad . Screening is substantially more cost-effective outside the United States . Whether population screening is justified, however, is uncertain pending conclusive data regarding the reduction in gastric cancer risk from antibiotics.

Biochem Biophys Res Commun, 1999 Jun 24, 260(1), 9 - 12
A G-CSF receptor-gyrase B fusion gene: A new type of molecular switch for expansion of genetically modified hematopoietic cells; Kume A et al.; We have developed a novel system for expansion of transduced hematopoietic cells . This system involves "selective amplifier genes" encoding fusion proteins between the granulocyte colony-stimulating factor receptor (Gcr) and the estrogen receptor (Er) . The GcrEr chimeric gene conferred estrogen-dependent growth ability on murine hematopoietic cells . Here, we constructed a modified "selective amplifier gene" to circumvent possible concerns with the Er/estrogen switching system . The bacterial gyrase B (Gyr) gene was fused to the Gcr gene, and the GcrGyr fusion construct was introduced into interleukin-3 (IL-3)-dependent Ba/F3 cells . The dimeric antibiotic coumermycin induced IL-3-independent growth in Ba/F3 cells expressing GcrGyr . This stimulatory effect was antagonized by an excess amount of novobiocin, a monomeric form of coumermycin . These results suggest the feasibility of using Gyr as a molecular switch to regulate a growth signal in hematopoietic cells .

Allergy, 1999 May, 54(5), 428 - 35
Occurrence of allergic conditions in asthmatics with analgesic intolerance; Kalyoncu AF et al.; BACKGROUND: The study aimed to determine whether allergic conditions accompany analgesic intolerance . METHODS: A total of 132 analgesic-intolerant patients with bronchial asthma admitted to the adult allergy unit from January 1991 to October 1997 and 103 patients with bronchial asthma randomly selected from among the asthmatics referred to our department between January and October 1997 were enrolled in the study . Those having analgesic intolerance and bronchial asthma were accepted as group I; patients having only asthma were accepted as group II . A standard questionnaire was completed for all the patients . Physical examination, routine skin prick tests, determination of total IgE levels and blood type, and oral analgesic provocation tests were also performed . RESULTS: The results showed that some allergic conditions were significantly more common in group I (22.7% and 7.8% for food allergy/intolerance {P<0.05}, 16.7% and 7.8% for antibiotic allergy, 16.7% and 2.9% for dermographism, 9.8% and 1.0% for metal allergy, and 9.1% and 1.0% for chronic urticaria for groups I and II, respectively {P<0.001}) . In addition, the mean of the total IgE level in the serum was higher in group I than group II (77.6 and 53.7 IU/ml; P<0.05), and the cumulative analgesic consumption was more in group I (14.2+/-17.1 and 9.1+/-12.5 boxes; P<0.05) . CONCLUSIONS: Dermographism; chronic urticaria; antibiotic, metal, and food allergy; high levels of total IgE; and a high amount of cumulative analgesic consumption may be the conditions accompanying analgesic intolerance in asthmatics.

Minerva Chir, 1999 Apr, 54(4), 245 - 50
{An update in the treatment of intra-abdominal abscesses}; Vadala G et al.; BACKGROUND AND AIMS: Intra-abdominal abscesses represent a relatively severe complication in gastroenterological surgery owing to their association with high levels of morbidity and mortality . METHODS: The authors report their experience between January 1990 and January 1996 in 11 patients with intra-abdominal abscesses secondary to emergency surgery for gastroenterology in 10 cases and gynecology in 1 case . After the lesion had been identified using ultrasonography and CT, it was emptied, washed with antibiotic and drained using Seldinger's ultrasonographic and CT-guided technique . Small abscesses (less than 5 mm) were completed removed . RESULTS: The following results were obtained: the immediate disappearance of pain and fever, accompanied by improved general conditions, restoration of canalisation and closure of the abscess cavity (on average between 10 and 15 days) . CONCLUSIONS: In conclusion, ultrasonographic-CT guided drainage of postoperative intra-abdominal abscesses, which were previously managed using surgical methods, appears to be the best treatment, relying on the use of imaging techniques and thereby allowing both morbidity and mortality to be reduced.

Pharm World Sci, 1999 Apr, 21(2), 74 - 9
Rational pharmacotherapy in The Netherlands: formulary management in Dutch hospitals; Fijn R et al.; A survey regarding the management of rational pharmacotherapy was conducted among all Dutch general hospitals in 1998 . The response was 99% (n = 120) . The presence of a drugs and therapeutics committee and antibiotic policies in Dutch general hospitals appears independent of hospital characteristics . However, formulary agreements and treatment guidelines are less likely to be present in hospitals that employ only 1 pharmacist or those served by community pharmacies . More than half of the hospitals claim to have restrictive formulary agreements . Large hospitals, hospitals in the eastern and southern provinces and those served by hospital pharmacies more often tend to have restrictive agreements compared to small hospitals, hospitals in the northern, central, and western provinces, and those served by community pharmacies . Various methods to impose restriction and ensure formulary compliance are mentioned . It must be noted that hospitals tend to operate rather solely regarding the large number of different formularies . Surprisingly just a small majority of pharmacists evaluates formulary agreements positively as a management tool . Many drawbacks appear to be present . The results of this survey indicate that in the future Dutch hospitals will favour disease management (treatment guidelines) over drug management (formulary agreements) in the management of rational pharmacotherapy and that information technology will be used to influence clinicians' prescribing behaviour.

Aust N Z J Ophthalmol, 1999 Apr, 27(2), 153 - 6
Conservative management of documented neuroretinitis in cat scratch disease associated with Bartonella henselae infection; Rosen BS et al.; BACKGROUND: Bartonella henselae has been identified as the causative agent of the neuroretinitis associated with cat scratch disease (CSD) . Immunofluorescent antibody tests with good sensitivity and specificity are available to aid in diagnosis . Despite diagnostic advances, optimal management remains controversial . We present a case of documented B . henselae macular neuroretinitis managed without antibiotics and discuss antibiotic use in this condition . METHODS: We examined a young woman with macular neuroretinitis and established a diagnosis of CSD . Management consisted of a review of the literature, followed by educating her about the condition and close observation . We documented the course of her disease . RESULTS: We diagnosed neuroretinitis associated with B . henselae infection based on immunofluorescent antibody titres and clinical presentation . Our patient's neuroretinitis resolved promptly without antibiotic therapy . CONCLUSIONS: Macular neuroretinitis in CSD can be satisfactorily diagnosed with the use of fluorescent antibodies in the appropriate clinical setting . Optimal treatment for the disease has not been established and observation combined with patient education remains an appropriate option . The self-limited nature of the disease implies that treatment studies not using controls must be interpreted with great caution . Adverse drug reactions and other iatrogenic complications can be reduced by limiting antibiotic use in settings where a meaningful treatment benefit has not been established.

Minerva Ginecol, 1999 Apr, 51(4), 139 - 43
{Preterm premature rupture of membranes in the 19th week of pregnancy . A clinical case}; Bastianelli C et al.; A case of premature rupture of membranes occurred at 19 weeks of pregnancy is reported . The patient underwent a genetic amniocentesis at 16 weeks of gestational age . During the hospitalization period, she presented amniotic fluid leakage responsible of olygohidramnios . She was treated with antibiotic, spasmolytic, tocolytic and cortisone therapy . All subsequent parameters were evaluated: blood cell count, heart rate frequency, body temperature . Ultrasound examinations were performed every two weeks . Cervical smears to detect infections were normal . Labour started at 28 weeks and the patient delivered spontaneously a 1010 g male baby, Apgar 4/8 . The heaviest complication was a cerebral hemorrhage and the subsequent frontoparietal hematoma which progressively reduced . To date the neurological prognosis is good.

Am J Med, 1999 Jun, 106(6), 670 - 6
Acute diarrhea: a practical review; Aranda-Michel J et al.; This review provides a practical, simple, and logical approach to the diagnosis and management of patients with acute infectious diarrhea, one of the most common diagnoses in clinical practice . Diarrhea in the immunocompromised host, traveler's diarrhea, and diarrhea in the hospitalized patient are also discussed . Most episodes of acute diarrhea are self-limited, and investigations should be performed only if the results will influence management and outcome . After an adequate history and physical examination, the clinician should be able to classify the acute diarrheal illness, assess the severity, and determine whether investigations are needed . Most patients do not require specific therapy . Therapy should mainly be directed at preventing dehydration . Various home remedies frequently suffice in mild, self-limited diarrhea . However, in large-volume, dehydrating diarrhea, oral rehydration solutions should be used, as they are formulated to stimulate sodium and water absorption . Antidiarrheal agents can be useful in reducing the number of bowel movements and diminishing the magnitude of fluid loss . The most useful agents are opiate derivatives and bismuth subsalicylate . Antibiotic therapy is not required in most patients with acute diarrheal disorders . Guidelines for their use are presented.

J Am Dent Assoc, 1999 Jun, 130(6), 832 - 6
Diagnosis and treatment of cutaneous facial sinus tracts of dental origin; Johnson BR et al.; BACKGROUND: Cutaneous draining sinus tracts of dental origin often are a diagnostic challenge . A delay in correctly diagnosing these types of lesions can result in ineffective and inappropriate treatment . CASE DESCRIPTION: The authors present five cases of facial lesions that were initially misdiagnosed as lesions of nonodontogenic origin . The correct diagnosis in each case was cutaneous sinus tract secondary to pulpal necrosis and suppurative apical periodontitis . All facial sinus tracts resolved after the patients received nonsurgical root canal therapy . CLINICAL IMPLICATIONS: As patients with cutaneous facial sinus tracts of dental origin often do not have obvious dental symptoms, possible dental etiology may be overlooked . Early correct diagnosis and treatment of these lesions can help prevent unnecessary and ineffective antibiotic therapy or surgical treatment.

Int J Mol Med, 1999 Jul, 4(1), 29 - 32
Apoptosis induced by propolis in human hepatocellular carcinoma cell line; Choi YH et al.; Propolis has been reported to exhibit a wide spectrum of activities including antibiotic, antiviral, anti-inflammatory, immunostimulatory and tumor carcinostatic properties . We showed propolis induced apoptosis in a human hepatoma cell line (SNU449) by FITC-Annexin V/PI staining . We also compared the apoptosis inducing effect between Korean and Commercial (Sigma # p-1010) propolis . There was no difference on apoptosis between them.

Neurosurgery, 1999 Jun, 44(6), 1263 - 5; discussion 1265-6
Cranial procedures without hair removal
Sheinberg MA, Ross DA.
OBJECTIVE: In 1992, Winston published the first large series of patients undergoing cranial neurosurgery without hair removal (Winston KR: Hair and neurosurgery . Neurosurgery 31:320-329, 1992) . Prompted by this report, the senior author began a prospective trial in 1992 of cranial neurosurgery without hair removal . METHODS: All patients undergoing elective cranial surgery were offered the opportunity to undergo surgery without hair removal . The protocol advocated by Winston was strictly followed in the first 100 patients but has subsequently been modified . Patients having only cranial procedures have their head prepared for 10 minutes with chlorhexidine and water followed by an isopropyl alcohol rinse . Patients having craniofacial procedures are prepared with iodophor . A single perioperative dose of prophylactic antibiotic is administered . RESULTS: We have performed 346 cranial operations without hair removal . These include craniotomy for tumor, trauma, and aneurysm (n = 115); epilepsy procedures, including depth, subdural strip, and grid electrode placement, lobectomy, and callosotomy (n = 95); functional procedures, including thalamotomy, pallidotomy, capsulotomy, and stereotactic biopsy (n = 84); ventriculoperitoneal shunts (n = 8); brain abscess aspiration or resection (n = 5); and miscellaneous other procedures (n = 10) . Twenty-nine patients underwent cranial base procedures in conjunction with an otolaryngologist and had the alternate preparation . There have been no infections and no other complications associated with not removing hair . CONCLUSION: Cranial surgery without hair removal is safe and is not associated with a discernible increased risk of infection . There are simple techniques for keeping hair out of the wound . Patients are highly desirous of keeping their hair and react very positively to this option . We advocate a greater practice of this technique in neurosurgery.

Infect Dis Obstet Gynecol, 1999, 7(3), 153 - 7
Prophylactic cefazolin in amnioinfusions administered for meconium-stained amniotic fluid; Edwards RK et al.; OBJECTIVE: To determine if amnioinfusion with an antibiotic solution decreased the rate of clinical chorioamnionitis and puerperal endometritis in patients with meconium-stained amniotic fluid . METHODS: Patients in labor at 36 weeks of gestation or greater with singleton pregnancies and meconium-stained amniotic fluid were randomized to receive either cefazolin, 1 g/1,000 mL, of normal saline (n = 90) or normal saline (n = 93) amnioinfusion . Rates of clinically diagnosed chorioamnionitis and endometritis and of suspected and culture-proven neonatal infection were determined . RESULTS: Between the study and control groups, the incidences of clinical chorioamnionitis (7.8% vs . 8.6%), endometritis (2.4% vs . 3.5%), aggregate intrauterine infection (10.0% vs . 11.8%), suspected neonatal infection (17.8% vs . 21.5%), and proven neonatal infection (0.0% vs . 2.2%) were not significantly different . CONCLUSIONS: Prophylactic use of cefazolin in amnioinfusions did not significantly reduce rates of maternal or neonatal infection in patients with meconium-stained amniotic fluid.

Jpn Heart J, 1999 Jan, 40(1), 91 - 6
Hypoglycemia induced by interaction between clarithromycin and disopyramide; Iida H et al.; A 59-year-old man receiving hemodialysis was hospitalized due to severe hypoglycemic attack . The patient had been treated with disopyramide (50 mg/day) because of paroxysmal atrial fibrillation . Hypoglycemia occurred after taking clarithromycin (CAM, 600 mg/day), a macrolide antibiotic . The serum disopyramide concentration reached 8.0 micrograms/ml (23.6 microM) in the presence of CAM, while it was 1.5 micrograms/ml before the addition of CAM . A 75 g oral glucose tolerance test and daily profiles of blood glucose value showed that blood glucose levels were significantly lower in the presence of CAM and disopyramide compared to that in the absence of these drugs . The Turner index in the presence of CAM and disopyramide was significantly higher than that in the absence of these drugs, suggesting that a toxic concentration of disopyramide enhanced insulin secretion, resulting in the induction of hypoglycemic attacks, in which the inhibitory effects of CAM on the hepatic chytochrome P-450 might be involved . QT and QTc intervals were prolonged in the presence of CAM and disopyramide, but torsades de points were not observed in this patient receiving nicorandil (15 mg/day) . Thus, it should be taken into account that life-threatening hypoglycemia may result from the interaction between clarithromycin and disopyramide.

Vestn Khir Im I I Grek, 1999, 158(2), 62 - 4
{The treatment of patients with acute appendicitis by a short-term stay in the hospital}; Komarov NV et al.; An analysis of results of treatment of 102 patients with acute appendicitis has shown that use of non-direct endolymphatic therapy decreases the amount of antibiotics and analgetics administered after surgery, leads to less frequency of postoperative complications and the patients can be discharged from the hospital within the first 6 days after operation.

Am J Obstet Gynecol, 1999 Jun, 180(6 Pt 1), 1499 - 503
Malignant melanoma of the ovary and exposure to clomiphene citrate: a case report and review of the literature; Fuller PN; OBJECTIVE: The purpose of this article is to present a case of metastatic malignant melanoma of the ovary, a review of the current literature, and current recommendations for preventative and consultative management . STUDY DESIGN: This is a case report and literature review . A 34-year-old woman had symptoms of pelvic abscess 1 month after clomiphene citrate stimulation for infertility . After a failed course of antibiotic therapy, an exploratory laparotomy was performed . Bilateral malignant melanomas of the ovary were discovered . The patient died 4 weeks later of disseminated metastases . Retrospectively, a history of a "mole" with unknown histopathologic characteristics had been removed from her arm 15 years earlier . A review of the literature was performed to provide current findings regarding malignant melanomas of the ovary, as well as to evaluate the potential relationship between the use of ovarian stimulating drugs and the development of melanomas . RESULTS: Melanomas account for 3% of cancers, but the incidence of melanoma is rising . Genital melanomas are uncommon; the primary site is the vulva . Primary malignant melanoma of the ovary is rare; however, delayed recurrence from a primary skin site with metastasis to the ovary is documented . The literature suggests a possible relationship between the use of clomiphene citrate and an increase in melanomas of the skin . CONCLUSION: The gynecologist, as a primary provider, must be aware of the increasing incidence of malignant melanoma, as well as the recommendations for prevention . The gynecologist, as a consultant, must be aware of the risk of delayed recurrence of malignant melanoma . The potential for development of melanomas associated with the use of ovarian stimulation for infertility needs further monitoring and analysis.

J Zoo Wildl Med, 1999 Mar, 30(1), 36 - 43
Clarithromycin pharmacokinetics in the desert tortoise (Gopherus agassizii); Wimsatt JH et al.; Clarithromycin is a new, safe orally administered macrolide antibiotic active against Mycoplasma sp . in humans . Single-dose and multidose pharmacokinetic parameters were determined for clarithromycin in wild-caught desert tortoises (Gopherus agassizii) seropositive for M . agassizii . Clarithromycin blood levels were measured in three tortoises for up to 72 hr after a single oral dose of 7.5 mg/kg . In a second group of six tortoises, levels were measured after a dose of 15 mg/kg . Noncompartmental iterative two-stage Bayesian and nonparametric expectation maximization pharmacokinetic parameters were determined for each animal assuming first order rate constants . At 15 mg/kg, the maximum concentration was 1.37 microg/ml, the time to maximum concentration was 8.0 hr, and a plasma half-life of 11.69 hr was derived from the latter method . The absorption constant was 0.08/hr, the absorption half-life was 8.47 hr, and the weight-normalized volume of distribution was 5.30 L/kg . Predictions derived by the latter method suggested a dosage of 15 mg/kg p.o . every 24 hr to achieve maximal blood levels of > or =1 microg/ml for multiple dosing . However, results from a preliminary multidose study with three tortoises indicate that the drug is accumulated; therefore, the predicted dose may be closer to 15 mg/kg p.o . every 2-3 days to maintain blood levels of 2-7.5 microg/ml . (For n = 3, 2-point linear regression median estimates for the apparent elimination rate constant (K) and half-life are 0.0227/hr and 30.52 hr, respectively.) This multidose accumulation reflects a slower apparent elimination than that predicted in the eight single-dose tortoises (i.e., K = 0.0593/hr, t1/2 = 11.69 hr) . This study highlights a potential pitfall of depending solely on single-dose studies and the potential value of oral administration in reptiles.

J Cardiovasc Pharmacol, 1999 Jun, 33(6), 829 - 35
Neointimal formation after balloon-induced vascular injury in Yucatan minipigs is reduced by oral rapamycin; Burke SE et al.; Rapamycin, a macrolide antibiotic known to prevent allograft rejection, is a potent inhibitor of cell proliferation . Therefore we studied the effects of orally administered rapamycin in a pig model of balloon injury in an attempt to reduce the cellular proliferation and neointimal formation thought to play a role in restenosis . Twenty Yucatan minipigs, divided into groups of 10 animals each, were subjected to balloon inflation of the carotid arteries . One group received the methylcellulose vehicle for rapamycin, whereas the second group was treated for a total of 31 days with 2.0 mg/kg of rapamycin administered daily by oral gavage . This dose and treatment regimen produced significant (p < 0.05) reductions in neointimal area (59%) and in the maximal thickness of the neointima (59%) when comparisons were made with vehicle-treated animals . These effects were accompanied by a significant increase in the lumen area in animals that received rapamycin (33%) . Medial area was decreased by 18% in these animals . Blood samples from rapamycin-treated pigs indicated peak concentrations of 1.87 +/- 0.45 and 1.70 +/- 0.24 ng/ml at 2 and 4 weeks after balloon angioplasty, respectively . Significant increases in blood pressure of 21 mm Hg and decreases in heart rate of 25 beats/min also were observed in rapamycin-treated animals relative to those that received vehicle . These results indicate that the antiproliferative effect of rapamycin can be demonstrated after oral dosing in a pig vascular injury model, suggesting a possible therapeutic utility for rapamycin or its analogs in patients undergoing balloon angioplasty.

Rev Clin Esp, 1999 Apr, 199(4), 193 - 7
{Practical considerations respecting the clinical use of serum cystatin C as a marker of glomerular filtration}; Riveiro Cruz A et al.; A curvilinear relationship of potential type was observed between serum concentrations of cystatine C and creatinine in 187 patients attended at our Nephrology Department . This relationship became linear when considering the reverse values, but the estimation error was much higher than what is clinically acceptable, which prevents the interconversion of values . In 78 critical patients, in whom an antibiotic therapeutic monitoring was being carried out, serum creatinine concentrations in the reference range were observed to be associated with pathologic concentrations of cystatine C . In 22 regularly hemodialysed patients, using Hemophan or Cuprophan membranes, increments of approximately 5% for cystatine C and beta 2-microglobuline in post-dialysis samples were observed . The chronic administration of inducer antiepileptic drugs, capable of modifying the concentration of different plasmatic proteins and reducing the serum concentration of creatinine, does not seem to limit the applicability of cystatine C as marker for glomerular filtration . The routine measurement of cystatine C seems to be warranted for estimating the glomerular filtration rate in patients in whom creatinine synthesis might be impaired.

J Am Pharm Assoc (Wash), 1999 May-Jun, 39(3), 388 - 94; quiz 423-4
Applying managed care performance measures in community pharmacy-based outcomes research; Capo KM et al.; OBJECTIVES: (1) To introduce the National Committee on Quality Assurance's (NCQA's) Health Employer Data and Information Set (HEDIS), a set of managed care performance measures, as a tool for conducting outcomes research in the community pharmacy; (2) To demonstrate the practical application of this tool by describing three outcomes research projects conducted in an independent community pharmacy . DESIGN: Review of three outcomes research projects based on HEDIS: (1) Increasing ACEI Use in Patients with Heart Failure, (2) Cardiovascular Telepharmacy Project, and (3) Pediatric Antibiotic Callback Program . SETTING: Independent community pharmacy . RESULTS: The "Effectiveness of Care" section of HEDIS was a practical tool for designing outcomes research projects in the community setting . Improved clinical and/or service outcomes were observed in two of the projects . The challenges faced in these projects were due to the methods of implementation, rather than to the HEDIS tool itself . These projects led to a number of "lessons learned" in the conduct of outcomes research in the community pharmacy setting . CONCLUSION: Community pharmacists can use NCQA's HEDIS as a tool to help gain acceptance of and reimbursement for pharmaceutical services through the formulation of outcomes projects that are of interest to managed care organizations (MCOs) seeking accreditation status . As pharmacists report their successes to MCOs, they may be better equipped to develop reimbursement strategies for services from MCOs through their demonstration of shared goals.

Hinyokika Kiyo, 1999 Apr, 45(4), 289 - 91
{Syphilitic orchitis: a case report}; Nakano Y et al.; Syphilitic orchitis is recently a rare disease in Japan . A 75-year-old man was referred to our hospital with the complaint of persistent swelling of the left scrotal contents in spite of prior antibiotic therapy . We suspected a testicular tumor because of lack of pain, and performed high orchiectomy . The specimen showed wide-ranged necrosis with a non-specific inflammatory change of the testis on hematoxylin-eosin stain . After performing analysis using a polymerase chain reaction method, we reached the final diagnosis of syphilitic orchitis.

J Am Coll Cardiol, 1999 Jun, 33(7), 2023 - 9
Value and limitations of the Duke criteria for the diagnosis of infective endocarditis; Habib G et al.; OBJECTIVES: The purpose of this study was to assess the value and limitations of Duke criteria for the diagnosis of infective endocarditis (IE) . BACKGROUND: Duke criteria have been shown to be more sensitive in diagnosing IE than the von Reyn criteria, but the diagnosis of IE remains difficult in some patients . METHODS: Both classifications were applied in 93 consecutive patients with pathologically proven IE . Blood cultures, and transthoracic and transesophageal echocardiography were performed in all patients . RESULTS: Sensitivities for the diagnosis of IE were 56% and 76% for von Reyn and Duke criteria, respectively . Fifty-two patients were correctly classified as "probable IE" by von Reyn and "definite IE" by Duke criteria (group 1) . However, discrepancies were observed in 41 patients . Eleven patients (group 2) were misclassified as "rejected" by von Reyn, but were "definite IE" by Duke criteria; this difference could be explained by negative blood cultures and positive echocardiogram in all patients . In eight patients (group 3), the diagnosis of IE was "possible" by von Reyn but "definite" by Duke criteria . This difference was essentially explained by the failure of the von Reyn classification to consider echocardiographic abnormalities as major criteria . Twenty-two patients (group 4) were misclassified as possible IE using Duke criteria, being false negative of this classification . Echocardiographic major criteria were present in 19 patients, but blood cultures were negative in 21 patients . The cause of negative blood cultures was prior antibiotic therapy in 11 patients and Q-fever endocarditis diagnosed by positive serology in three cases . CONCLUSIONS: Twenty-four percent of patients with proved IE remain misclassified as "possible IE" despite the use of Duke criteria, especially in cases of culture-negative and Q-fever IE . Increasing the diagnostic value of echographic criteria in patients with prior antibiotic therapy and typical echocardiographic findings and considering the serologic diagnosis of Q fever as a major criterion would further improve the clinical diagnosis of IE.

Acta Otorhinolaryngol Ital, 1998 Oct, 18(5), 332 - 7
{Septic thrombophlebitis of the internal jugular vein due to Fusobacterium necrophorum (Lemierre's syndrome): case report and review of literature}; Ianniello F et al.; Lemierre's syndrome is an uncommon clinical entity . It is characterized by oropharyngeal infection followed by septic thrombophlebitis of the jugular vein with embolization to the lungs and other organs . It is usually due to Fusobacterium necrophorum . Although Lemierre's syndrome is rare, it is potentially fatal . It is important for clinicians to recognize and treat it appropriately . With prompt recognition, abscess drainage with possible ligation of the internal jugular vein and appropriate antibiotic coverage complete recovery can be achieved in most patients.

J Biotechnol, 1999 Apr 15, 69(2-3), 215 - 26
Changes during subclone development and ageing of human antibody-producing recombinant CHO cells; Strutzenberger K et al.; Some of the problems encountered with human or human-mouse heterohybridomas, such as low growth rates and high serum requirements, have led to the increased use of recombinant cell lines for production of human antibodies . To evaluate the suitability of such alternative cell lines for the production of human antibodies we have analysed several subclones with differing specific production rates of a recombinant CHO cell line . Gene copy number and site of chromosomal integration for the light and heavy chain and the dhfr gene were determined by in-situ hybridisation . Specific mRNA content was analysed by Northern blot . In addition the intracellular content in light and heavy chain was measured by flow cytometry and the specific secretion rates were determined . The stability of gene expression was followed in the highest producing subclone for over a year . As previously seen in heterohybridoma cells a high expression rate of light chain is beneficial in speeding up secretion rates of whole antibody . When grown in the presence of G418 and methotrexate the amplified gene copies in the genome of recombinant CHO cells were stable over more than 100 passages . However, the expression of light chain, and with it the secretion rate, decreased with time . The low intracellular concentration of light chain resulted in accumulation of heavy chain in the endoplasmic reticulum due to retention by chaperones . The specific secretion rate decreased by 50% after 100 passages . When no G418 or methotrexate were present 75% of the gene copies were lost after 100 passages.

Biochemistry, 1999 Jun 8, 38(23), 7462 - 9
Elucidation of a monovalent cation dependence and characterization of the divalent cation binding site of the fosfomycin resistance protein (FosA); Bernat BA et al.; The fosfomycin resistance protein FosA is a member of a distinct superfamily of metalloenzymes containing glyoxalase I, extradiol dioxygenases, and methylmalonyl-CoA epimerase . The dimeric enzyme, with the aid of a single mononuclear Mn2+ site in each subunit, catalyzes the addition of glutathione (GSH) to the oxirane ring of the antibiotic, rendering it inactive . Sequence alignments suggest that the metal binding site of FosA is composed of three residues: H7, H67, and E113 . The single mutants H7A, H67A, and E113A as well as the more conservative mutants H7Q, H67Q, and E113Q exhibit marked decreases in the ability to bind Mn2+ and, in most instances, decreases in catalytic efficiency and the ability to confer resistance to the antibiotic . The enzyme also requires the monovalent cation K+ for optimal activity . The K+ ion activates the enzyme 100-fold with an activation constant of 6 mM, well below the physiologic concentration of K+ in E . coli . K+ can be replaced by other monovalent cations of similar ionic radii . Several lines of evidence suggest that the K+ ion interacts directly with the active site . Interaction of the enzyme with K+ is found to be dependent on the presence of the substrate fosfomycin . Moreover, the E113Q mutant exhibits a kcat which is 40% that of wild-type in the absence of K+ . This mutant is not activated by monovalent cations . The behavior of the E113Q mutant is consistent with the proposition that the K+ ion helps balance the charge at the metal center, further lowering the activation barrier for addition of the anionic nucleophile . The fully activated, native enzyme provides a rate acceleration of >10(15) with respect to the spontaneous addition of GSH to the oxirane.

J Endourol, 1999 Apr, 13(3), 147 - 50
Extracorporeal shockwave lithotripsy in the pediatric population; Demirkesen O et al.; BACKGROUND: Shockwave lithotripsy (SWL) is being used increasingly as a therapeutic modality for childhood urolithiasis . We reported our experience and results of SWL in the pediatric population . METHODS: The 59 renal units (RU) of 54 patients were retrospectively reviewed . The mean patient age was 10+/-3.5 years . All patients were treated with the Lithostar lithotripter in outpatient settings . Those with positive culture results were treated under appropriate antibiotic coverage . Seven patients were treated under general anesthesia and the rest under sedoanalgesia . Shielding of the lung fields or gonads was not used . For the upper pole stones, protection of the lungs was accomplished by elevating the upper half of the body with supportive pillows, thus moving the kidney away from the lung fields . Six RUs were catheterized via double-pigtail ureteral catheters or by percutaneous nephrostomy tube prior to treatment . The average stone load was 1.8+/-2.5 cm2 . RESULTS: Patients were treated with an average of 2.5 sessions . A total of 1000 to 2500 shockwaves were delivered between 14.5 and 17.8 kV . Routine spasmolytic treatment was not initiated . The stone-free rate was 64%, and clinically insignificant residual fragments (CIRF) were present in 29% of RUs; thus, the success rate was 93% . Fever that necessitated hospitalization occurred in one patient . No other complications were seen except skin bruising and early hematuria . CONCLUSION: Shockwave lithotripsy is a safe and effective treatment modality for childhood stones of appropriate size and radiologic characteristics.

Anesteziol Reanimatol, 1999 Mar-Apr, (2), 19 - 22
{Prolonged regional intra-arterial therapy in multimodal treatment of patients with severe skeletal trauma}; Khomutov VA et al.; A total of 108 victims with open fractures of long tubular bones of different localization are examined . Regional intraarterial therapy was added to their treatment protocols . Stable functional disorders in local hemodynamics in these patients impede the repair processes and can lead to development of infectious complications . Regional intraarterial therapy allows early elimination of hemodynamic disorders, selective antibiotic therapy, and improves the adaptation potential of the immune system.

J Allergy Clin Immunol, 1999 Jun, 103(6), 1031 - 5
Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy; Fost DA et al.; BACKGROUND: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma . Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance . OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects . METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic . Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma . Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course . Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy . RESULTS: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations . CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects . Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma . To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.

Jpn J Thorac Cardiovasc Surg, 1999 Apr, 47(4), 171 - 3
Post-parturition infectious endocarditis in a patient with a normal mitral valve; Murai N et al.; A 29-year-old woman with no history of heart disease was admitted for the treatment of congestive heart failure . Six months earlier, she had given birth, then 20 days later developed a fever and cardiac failure ensued . An echocardiogram demonstrated severe mitral valve regurgitation . Her blood cultures were positive, and we made a diagnosis of mitral valve regurgitation due to infectious endocarditis . Despite treatment for congestive heart failure and antibiotic therapy, resulting in negative blood cultures, her congestive heart failure did not improve, and vegetation on the mitral valve was observed by echocardiography . We successfully removed the infected tissue with mitral valve plasty.

Acta Virol, 1998 Dec, 42(6), 383 - 8
Inhibition of Mayaro virus replication by cerulenin in Aedes albopictus cells; Pereira HS et al.; The antibiotic cerulenin, an inhibitor of lipid synthesis, was shown to suppress Mayaro virus replication in Aedes albopictus cells at non-cytotoxic doses . Cerulenin blocked the incorporation of {3H}glycerol into lipids when present at any time post infection (p.i.) . Cerulenin added at the beginning of infection inhibited the synthesis of virus proteins . However, when this antibiotic was added at later stages of infection, it had only a mild effect on the virus protein synthesis . The possibility that cerulenin acts by blocking an initial step in the Mayaro virus replication after virus entry and before late viral translation is discussed.

J Biol Chem, 1999 Jun 11, 274(24), 17353 - 7
A novel labeling approach supports the five-transmembrane model of subunit a of the Escherichia coli ATP synthase; Wada T et al.; Cysteine mutagenesis and surface labeling has been used to define more precisely the transmembrane spans of subunit a of the Escherichia coli ATP synthase . Regions of subunit a that are exposed to the periplasmic space have been identified by a new procedure, in which cells are incubated with polymyxin B nonapeptide (PMBN), an antibiotic derivative that partially permeabilizes the outer membrane of E . coli, along with a sulfhydryl reagent, 3-(N-maleimidylpropionyl) biocytin (MPB) . This procedure permits reaction of sulfhydryl groups in the periplasmic space with MPB, but residues in the cytoplasm are not labeled . Using this procedure, residues 8, 27, 37, 127, 131, 230, 231, and 232 were labeled and so are thought to be exposed in the periplasm . Using inside-out membrane vesicles, residues near the end of transmembrane spans 1, 64, 67, 68, 69, and 70 and residues near the end of transmembrane spans 5, 260, 263, and 265 were labeled . Residues 62 and 257 were not labeled . None of these residues were labeled in PMBN-permeabilized cells . These results provide a more detailed view of the transmembrane spans of subunit a and also provide a simple and reliable technique for detection of periplasmic regions of inner membrane proteins in E . coli.

Med Arh, 1999, 53(1), 13 - 7
{Modern methods in the diagnosis of tuberculosis: PCR--polymerase chain reaction}; Zvizdic S et al.; The diagnosis of tuberculosis depends on many factors but essentially on the detection of mycobacteria, their identification to the species level, and their susceptibility to major antituberculous drugs . The classic tests (direct examination-Ziehl-Neelsen, conventional culture and antibiotic susceptibility tests) are combined with modern tests (the molecular tests such as genomic amplification /PCR/ direct from clinical samples) . By Polymerase Chain Reaction (PCR) over a billion identical bacteria could be multiplied from a single DNA molecule . These modern tests shortened diagnostics duration from several weeks to one or two days . The sensitivity of PCR test was 97% for Z-N positive, 68% for Z-N negative samples while specificity was 99% either for Z-N positive or negative samples.

IEEE Trans Biomed Eng, 1999 Jun, 46(6), 663 - 9
Innovative ambulatory drug delivery system using an electrolytic hydrogel infusion pump; Kim HC et al.; This report describes an ambulatory infusion device developed to provide parenteral drug delivery at a precisely controlled rate . The device is based on the innovative and unique concept of utilizing electrohydrolysis of a negatively charged hydrogel . The system consists of two modules: a pump unit and an electronic control unit . The pump module, which can be a disposable unit, contains medication separated by a flexible membrane from a gas generating chamber; this latter is an electrolytic cell comprising a hydrogel block and two platinum electrodes . The microcontroller-based control module is constructed with a user interface which includes input keys and a liquid crystal display, as well as a control to alter driving current level, depending on the infusion rate required . A microprocessor instantaneously calculates the current level required; this is based on operator-selected infusion rate, ambient pressure, and temperature sensor output . The accuracy and precision of the device were verified for all flow rates and for different environmental conditions; in vitro test results showed acceptable accuracy with less than +/- 5% error over the whole operating range of 0.1-100 {ml/h} . The device is small, lightweight, simple and easy to manufacture, and is also designed to be comfortably and conveniently worn by patients . It can be used for a variety of regimens including, for example, chemotherapy, insulin delivery, and pain management, antibiotic and AIDS therapy.

Tidsskr Nor Laegeforen, 1999 Apr 20, 119(10), 1456 - 9
{Rheumatic fever and rheumatic heart disease in Northwest Russia}; Augestad KM et al.; 296 patients who were operated between 1965 and 1993 with mitral commissurotomy, were included in this retrospective study of rheumatic heart disease in North-West Russia . There were 117 (39.5%) reported cases of acute rheumatic fever, with either polyarthritis (n = 88), carditis (n = 23), or Sydenham's chorea (n = 6) . There were no reported cases of erythema marginatum and subcutaneous nodules . The first case of acute rheumatic fever in our patients was in 1924 . More than 50% of the patients (164) did not get the diagnosis acute rheumatic fever, and became aware of their rheumatic heart disease only when symptoms of mitral stenosis appeared . 15 patients had a subclinical attack of rheumatic fever, i.e . not all of Jones' criteria were fulfilled . At onset of acute rheumatic fever, the mean age was 15 years, when valvular disease was confirmed 24 years, and 33 years at mitral surgery . Dyspnea (n = 293) was the most common symptom of mitral stenosis, followed by atrial fibrillation (n = 105) . 15 patients developed cerebral stroke . The Archangel Health Region has one of the highest prevalences of rheumatic heart disease in Europe (3.7/1,000 in those above 16 years of age, 1993) . There is high mortality and the disease develops rapidly.

Przegl Lek, 1998, 55(12), 639 - 44
{Postoperative wound infections . IV . Flora and clinical course of postoperative wound infection}; Anielski R et al.; Each wound infection may be coursed in few clinical manifestations and may concern either skin with subcutaneous tissue (superficial infection) or deeper layers-fascias, muscles (deep infection) . The aim of this study was to evaluate the form of infection and its clinical course, and moreover, to find the specific flora of infected wounds . The material was 1527 surgically treated patients in the 3rd Surgical Department of the Collegium Medicum of the Jagiellonian University during one year . 66 patients with wounds of the head and 7 patients who died within first three days after surgery without wound infection signs were excluded from the study population . The healing of each wound was observed during the patient's hospitalisation and 30 days after discharge from hospital, and in orthopedic patients 6 months after discharge . The total number of 132 infected wounds was identified . The population of 1352 wounds healed without any complications was a control group . All the data were recorded in a Wound Infection Register Card and were collected in the computer database . The data were statistically analysed . Relationships between single factors and postoperative wound infection were evaluated using chi-square statistics and in the small number Fisher's exact probability test . Analysis of variance was used for continuous variables . Odds ratios and corresponding 95% confidence intervals were computed for all variables . Postoperative wound infection was found in 132 (8.9%) cases, including 76 (57.6%) in males and 56 (42.4%) in females . The average age was 50.9 years . The period of hospitalisation ranged from 3 to 119 days, with the mean of 31.9 days in comparison to 16.3 days in the control group.

Biomaterials, 1999 Apr, 20(8), 711 - 9
Development of a calcium phosphate-gelatin composite as a bone substitute and its use in drug release; Yaylaoglu MB et al.; This study was carried out to develop a calcium phosphate-gelatin composite implant that would mimic the structure and function of bone for use in filling voids or gaps and to release bioactive compounds like drugs, growth hormones into the implant site to assist healing . XDS analysis of the synthesized calcium phosphate revealed a calcium to phosphorus molar ratio of ca . 2.30, implying a less erodible material than hydroxyapatite (1.67) . Release of the antibiotic gentamicin from the implant was with a burst, whether in situ or in vivo, followed by an almost constant release for about three months . It was found that the release rate could be decreased by increasing the density of the gelatin membrane . Upon implantation into rabbit tibia the release duration was substantially shortened (to about 4 weeks) with respect to the in situ tests basically due to the degradation of gelatin . In vivo studies with rabbits confirmed this degradation . The composite was perfectly biocompatible as shown by the histological studies . It, thus, has a great potential as a bone substitute material.

Eval Health Prof, 1998 Dec, 21(4), 514 - 24
Quality of care improvements for patients with pneumonia . Florida Medical Quality Assurance, Inc.
Infectious agents that play a role in atherosclerosis and vasculopathies . What are they? What do we do about them?
University of Minnesota, Minneapolis, Minnesota, USAMuch of the published data suggest a link between herpes infection and atherosclerosis, as well as herpes infection and restenosis . Mechanistically, herpesvirus has been shown to promote inflammation, thrombin generation and platelet binding, and infected cells have been shown to be resistant to apoptosis . There is also good evidence of a link between Chlamydia pneumoniae infection and atherosclerosis . In preliminary studies, antichlamydial antibiotic intervention has been shown to reduce significantly the incidence of cardiac events in patients with coronary artery disease and in myocardial infarction survivors.

Mutat Res, 1999 May 19, 426(2), 159 - 61
Pollution monitoring of three rivers passing through Fuzhou City, People's Republic of China; Zeng D et al.; The Tradescantia-micronucleus (Trad-MCN) bioassay was used to determine the pollution levels of three rivers passing through Fuzhou city . Results indicate that all three rivers are polluted but at different levels . They are ranked as follows: Antai River > Baima River > Jinan River . Positive results were obtained when full strengths of the water samples were used to treat the plant cuttings when compared with the negative control (tap water) group . Negative responses were obtained when the Baima and Jinan river water was diluted to 50% but not for the sample from the Antai river . Micronuclei frequencies of the Antai river group were higher than the positive control using the Ping-Yang antibiotic drug (Huapei Drug Manufacturer) at 0.2 microg/ml concentration .

Biochemistry, 1999 May 18, 38(20), 6489 - 98
Backbone dynamics of detergent-solubilized alamethicin from amide hydrogen exchange measurements; Yee A et al.; Alamethicin is a 20 amino acid antibiotic peptide produced by the soil fungus Trichoderma viride . The peptide inserts into bacterial membranes and self-associates to form ion channels, but the details of this process are unknown . Residue-specific acid- and base-catalyzed exchange data were obtained for 16 of 18 backbone amides of alamethicin dissolved in sodium dodecyl sulfate micelles using high-resolution 2-dimensional heteronuclear nuclear magnetic resonance spectroscopy . To facilitate interpretation of the exchange data, we synthesized N-acetyl-alpha-aminoisobutyric acid-N'-methyl and N-acetyl-alanine-N'-methyl and measured the pD dependence of their hydrogen-deuterium exchange rates to determine the sequence-dependent inductive and steric effects of the alpha-aminoisobutyric acid residue . Intramolecular H-bonding in alamethicin was monitored through the exchange parameters kmin (minimum exchange rate) which indicate that the backbone is significantly more stable than the backbones of alanine-based helical peptides . Rapid exchange at Gly-11 suggests a highly local conformational flexibility in the middle of the peptide . Interactions with the detergent micelle were revealed by the exchange parameters pDmin (pD of minimum exchange) which suggest that the N-terminus of alamethicin interacts more strongly with the detergent micelle than does the C-terminus . A periodicity in pDmin difference data reveals that one surface of the helix interacts more strongly with the micelle . The surface consists of residues 1, 5, 9, 13, 16, and 20 . The opposite face of the helix contains several polar residues (two glutamines and a glycine), suggesting that, on average, this face of the helix is directed toward the solvent . These results serve as a model for the interaction of the peptide with membranes containing anionic lipid . In combination with published molecular dynamics simulations {Gibbs et al . (1997) Biophys . J . 72, 2490-2495}, the present results also offer insight into the mechanisms of hydrogen-deuterium exchange in helical peptides.

J Cardiovasc Surg (Torino), 1999 Apr, 40(2), 229 - 31
Simultaneous surgery for infective endocarditis and endophthalmitis; Matsuda H et al.; A 54-year-old woman was diagnosed as having septicemia secondary to infective endocarditis with aortic regurgitation which was complicated by endophthalmitis . Her septicemia was controlled by intravenous antibiotic therapy . Then the localized eye infection and the aortic regurgitation with a massive vegetation were surgically treated simultaneously . She had no relapse of infection after intensive postoperative antibiotic therapy.

J Neurochem, 1999 Jun, 72(6), 2256 - 63
Radicicol potentiates neurotrophin-mediated neurite outgrowth and survival of cultured sensory neurons from chick embryo; Sano M et al.; Radicicol, an antifungal antibiotic with markedly low toxicity, is a potent inhibitor of the Src family of protein tyrosine kinases and causes morphological reversion of v-src-transformed fibroblasts . Recently, this antibiotic was also found to inhibit Raf kinase . In the present study, we found that nanomolar concentrations of radicicol (10 ng/ml) enhanced the survival and neurite outgrowth of neurons from embryonic chick dorsal root ganglia (DRGs) and sympathetic ganglia . It potentiated the trophic effects of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 on the cultured DRG neurons . This concentration of radicicol did not alter the tyrosine phosphorylation of Trk receptors or the activity of mitogen-activated protein (MAP) kinases . Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), did not inhibit radicicol, excluding the involvement of PI3-kinase in the radicicol-dependent trophic actions . These results suggest that radicicol mediates neuronal growth presumably via a mechanism not involving the activation of Trk receptors, MAP kinase, or PI3-kinase.

Z Naturforsch {C}, 1999 Mar-Apr, 54(3-4), 271 - 7
The anticancer drug adriamycin interacts with the human erythrocyte membrane; Suwalsky M et al.; Adriamycin is an aminoglycosidic anthracycline antibiotic widely used in the treatment of cancer . Increasing reports point to the involvement of cell membranes in its mechanism of action . The interaction of adriamycin with human erythrocytes was investigated in order to determine the membrane binding sites and the resultant structural perturbation . Electron microscopy revealed that red cells incubated with the therapeutical concentration of the drug in human plasma changed their discoid shape to both stomatocytes and echinocytes . According to the bilayer couple hypothesis, this means that adriamycin was incorporated into either the inner or outer leaflets of the erythrocyte membrane . To explain this unusual result, the drug was incubated with molecular models . One of them consisted of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) multilayers, representative of phospholipid classes located in the outer and inner leaflets of the erythrocyte membrane, respectively . X-ray diffraction showed that adriamycin interaction perturbed the polar head and acyl chain regions of both lipids . Fluorescence spectroscopy on another model, consisting of DMPC large unilamellar vesicles (LUV), confirmed the X-ray results in that adriamycin fluidized its hydrophobic moiety . It is concluded that adriamycin incorporates into both erythrocyte leaflets affecting its membrane structure.

Cutis, 1999 May, 63(5), 267 - 70
Subcutaneous Fusarium foot abscess in a renal transplant patient; Girardi M et al.; Fusarium species are ubiquitous plant and grain phytopathogens that rarely cause opportunistic infections in immunocompromised patients . While disseminated Fusarium infections are almost always fatal, localized infections may be responsive to a combination of systemic antibiotic therapy and surgical debridement . We present a diabetic renal transplant patient who developed a foot abscess due to Fusarium solani . Infection persisted despite aggressive surgical debridement and a 3-month course of intravenous liposomal amphotericin B.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 1999 May, 87(5), 600 - 4
Autosomal dominant osteosclerosis: report of a kindred; Curran AE et al.; Autosomal dominant osteosclerosis (ADO), a rare inherited craniotubular bone disorder, is a generalized hyperostosis that manifests itself as increased cortical thickening of the skull, mandible, metacarpals, metatarsals, long bones, vertebral bodies, ribs, and clavicles . Jaw abnormalities, which clinically resemble the widening and deepening of the mandible seen in cherubism, begin in childhood and have been reported to stabilize after puberty . Teeth and alveolar bone are normal . ADO must be distinguished from Van Buchem's disease, which is characterized by elevated serum alkaline phosphatase, neurologic complications, exopthalmos, periosteal excrescences, and an autosomal recessive pattern of inheritance, as well as from other craniotubular bone disorders such as osteopetrosis . We present clinical and radiographic documentation of members of a kindred representing 4 generations affected with ADO . At initial examination of the proband, a differential diagnosis included cherubism, fibrous dysplasia, osteopetrosis, and Paget's disease . Radiographic examination revealed extensive radiopacity of the inferior border and basal bone of the mandible . The proband's clavicles and humerus were also affected . All family members examined were similarly affected and had mandibular and palatal tori . Authors of a previously published report on the dental and dentoalveolar management of patients with craniotubular bone disorders have recommended prophylactic antibiotics to minimize risk of osteomyelitis in all such cases . The members of our kindred received extensive dental treatment before diagnosis, including extractions of severely carious teeth, preprosthetic dentoalveolar surgery, and endodontic therapy; there was no incidence of osteomyelitis or postsurgical complications . Therefore, the use of prophylactic antibiotics may not be warranted in patients with ADO who have otherwise normal medical histories.

Ned Tijdschr Geneeskd, 1999 Apr 10, 143(15), 769 - 72
{Immunology in medical practice . XVIII {correction of XVII} . Children with recurrent airway problems: asthma is not always the cause; Arets HG et al.; Three children, two boys aged 16 and 11 years and a girl aged 16 years, with symptoms resembling asthma had been treated for years with inhaled corticosteroids and beta 2-sympathicomimetics without satisfactory results . It was found that the antibody production after vaccination with 23-valent pneumococcal vaccine was impaired . The symptoms diminished during maintenance treatment with antibiotics in two children and with intravenous immunoglobulins in one . In patients with recurrent respiratory problems, but no specific history of asthma, immunological investigation is warranted, especially in patients whose 'asthma' is accompanied by respiratory infections . When treated for their immunodeficiency these patients show remarkable improvement and the need for steroids often disappears.

Appl Environ Microbiol, 1999 Jun, 65(6), 2716 - 22
Increase in alfalfa nodulation, nitrogen fixation, and plant growth by specific DNA amplification in Sinorhizobium meliloti; Castillo M et al.; To improve symbiotic nitrogen fixation on alfalfa plants, Sinorhizobium meliloti strains containing different average copy numbers of a symbiotic DNA region were constructed by specific DNA amplification (SDA) . A DNA fragment containing a regulatory gene (nodD1), the common nodulation genes (nodABC), and an operon essential for nitrogen fixation (nifN) from the nod regulon region of the symbiotic plasmid pSyma of S . meliloti was cloned into a plasmid unable to replicate in this organism . The plasmid then was integrated into the homologous DNA region of S . meliloti strains 41 and 1021, which resulted in a duplication of the symbiotic region . Sinorhizobium derivatives carrying further amplification were selected by growing the bacteria in increased concentrations of an antibiotic marker present in the integrated vector . Derivatives of strain 41 containing averages of 3 and 6 copies and a derivative of strain 1021 containing an average of 2.5 copies of the symbiotic region were obtained . In addition, the same region was introduced into both strains as a multicopy plasmid, yielding derivatives with an average of seven copies per cell . Nodulation, nitrogenase activity, plant nitrogen content, and plant growth were analyzed in alfalfa plants inoculated with the different strains . The copy number of the symbiotic region was critical in determining the plant phenotype . In the case of the strains with a moderate increase in copy number, symbiotic properties were improved significantly . The inoculation of alfalfa with these strains resulted in an enhancement of plant growth.

MLO Med Lab Obs, 1999 Jan, 31(1), 22 - 5, 53
Overcoming geographic isolation; Van Leeuwen A et al.; There are a lot of advantages to living in an isolated area, away from the hustle and bustle of the big city . We work hard to provide services more commonly located in a metropolitan area . There is satisfaction in being self-sufficient and able to spread your wings and start a new venture such as an off-campus diagnostic center or a courier route . We enjoy certain advantages in this environment . Changes in medical care delivery systems get to us slowly, giving us time to plan for the impact . Antibiotic-resistant organisms are slower to move in and are easier to control . The blood donor population is loyal and at a low risk for disease . Community involvement in many activities is easy to find and major cultural and sports events are within 1-3 hour's drive in any direction . All these factors combine to make our remote facility an attractive, yet challenging place to work.

Curr Microbiol, 1999 Jun, 38(6), 335 - 41
Expression of human growth hormone by the eukaryotic alga, Chlorella; Hawkins RL et al.; A method to use Chlorella to express a recombinant heterologous protein that can be recovered from the extracellular medium has been developed . Plasmids are constructed with an extracellular secretion signal sequence inserted between a promoter region and a gene for human growth hormone (hGH) . The plasmids also contain a Kanr region which confers resistance to the antibiotic G418 . Protoplasts are prepared by enzymatic treatment, and the plasmid is introduced by incubation of the protoplasts with polyethylene glycol and dimethyl sulfoxide . Cells are then grown in the presence of G418, and the medium is collected from 6 days after transfection . hGH is measured by immunoassay, and values for expressed hGH of about 200-600 ng/ml are obtained.

Blood, 1999 Jun 1, 93(11), 3678 - 84
Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamicin immunoconjugate; Sievers EL et al.; Leukemic blast cells express the CD33 antigen in most patients with acute myeloid leukemia (AML), but this antigen is not expressed by hematopoietic stem cells . We conducted a study to determine whether normal hematopoiesis could be restored in patients with AML by selective ablation of cells expressing the CD33 antigen . In a dose escalation study, 40 patients with relapsed or refractory CD33(+) AML were treated with an immunoconjugate (CMA-676) consisting of humanized anti-CD33 antibody linked to the potent antitumor antibiotic calicheamicin . The capacity of leukemic cells to efflux 3, 3'-diethyloxacarbocyanine iodide (DiOC2) was used to estimate pretreatment functional drug resistance . Leukemia was eliminated from the blood and marrow of 8 (20%) of the 40 patients; blood counts returned to normal in three (8%) patients . A high rate of clinical response was observed in leukemias characterized by low dye efflux in vitro . Infusions of CMA-676 were generally well tolerated, and a postinfusion syndrome of fever and chills was the most common toxic effect . Two patients who were treated at the highest dose level (9 mg/m2) were neutropenic >5 weeks after the last dose of CMA-676 . These results show that an immunoconjugate targeted to CD33 can selectively ablate malignant hematopoiesis in some patients with AML.

Am J Orthop, 1999 May, 28(5), 301 - 3
Open clavicle fractures: a case report; Simon RG et al.; Open fractures of the clavicle are rare, whereas closed fractures are quite common . Presented here is a case report of a grade IIIA open clavicle fracture . After reviewing the literature, there appears to be little information on the treatment or outcome of these fractures . One can only surmise that the outcome and complications are similar to those of other open fractures.

Respir Care Clin N Am, 1999 Jun, 5(2), 203 - 19
Hyperbaric oxygen in the treatment of life-threatening soft-tissue infections; Clark LA et al.; Necrotizing soft-tissue infections are rapidly spreading bacterial infections that account for a relatively small proportion of infections, but are aggressive in nature and nearly uniformly fatal if left untreated . Prompt recognition, antibiotic therapy, aggressive surgical debridement, and hyperbaric oxygen (HBO) therapy have reduced the mortality resulting from these infections . Oxygen, at increased pressures, augments tissue oxygen partial pressure, allowing increased bacterial killing by providing substrate for the formation of oxygen free radicals and augmenting respiratory burst . During the healing process, hyperoxia causes increased formation of capillaries for oxygen, nutrient, and antibiotic delivery, leading to increased efficacy of some antibiotics in the high oxygen environment, and possibly more rapid overall wound healing . Although there are no randomized trials of HBO in these infections, in vitro data and meta-analysis of clinical cases strongly support the use of HBO.

J Biomol Struct Dyn, 1999 Apr, 16(5), 1097 - 106
Effect of in vivo histone hyperacetylation on the state of chromatin fibers; Krajewski WA; We evaluated the contribution of in vivo histone acetylation to the folding of chromatin into its higher-order structures . We have compared high-order folding patterns of hyperacetylated vs . unmodified chromatin in living green monkey kidney cells (CV1 line) using intercalator chloroquine diphospate to induce alterations in the twist of internucleosomal linker DNA . We have shown that histone hyperacetylation induced by antibiotic Trichostatin A significantly alters intercalator-mediated chromatin folding pattern.

Can J Gastroenterol, 1999 Apr, 13(3), 213 - 7
Canadian Helicobacter pylori Consensus Conference update: infections in adults . Canadian Helicobacter Study Group; Hunt RH et al.; The first Canadian Helicobacter pylori Consensus Conference took place in April 1997 . The initial recommendations of the conference were published in early 1998 . An update meeting was held in June 1998, and the present paper updates and complements the earlier recommendations . Key changes included the following: the recommendation for testing and treating H pylori infection in patients with known peptic ulcer disease was extended to testing and treating patients with ulcer-like dyspepsia; it was decided that the urea breath test (not serology) should be used for routine diagnosis of H pylori infection unless endoscopy is indicated for another reason; and recommended therapies were a twice daily, seven-day regimen of a proton pump inhibitor (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) or ranitidine bismuth citrate 400 mg, plus clarithromycin 500 mg and amoxicillin 1000 mg, or plus clarithromycin 500 or 250 mg and metronidazole 500 mg . The need was reiterated to have funding for readily accessible, accurate testing for H pylori infection with the urea breath test . It was strongly recommended that regional centres be established to monitor the prevalence of antibiotic-resistant H pylori infections . The initial consensus document referred to pediatric issues that were not addressed in this update but were the subject of a subsequent Canadian Helicobacter Study Group meeting, and will be published later in 1999.

Dent Clin North Am, 1999 Apr, 43(2), 217 - 29
Preanesthetic evaluation; Latham LB; A thorough preanesthetic evaluation is the most important function an anesthesiologist can perform to prevent anesthetic morbidity and mortality and ensure a smooth course of anesthetic administration . This evaluation is best accomplished by a thoughtful review of the patient's history, examination of the patient's airway, and anticipation of the effect of anesthesia on the patient.

J Cataract Refract Surg, 1999 May, 25(5), 725 - 7
Bacterial endophthalmitis after suture removal; Culbert RB et al.; We present 3 cases of endophthalmitis following suture removal after cataract surgery . In all cases, prophylactic antibiotics had been used . Treatment included vitreous tap and intravitreal antibiotic injection, with only 1 of the 3 patients regaining good visual acuity . Because povidone-iodine 5% is more effective at decreasing conjunctival bacterial counts than topical antibiotics, we recommend this method of conjunctival preparation before suture removal.

J Mol Biol, 1999 May 14, 288(4), 521 - 38
Decay of rplN and lacZ mRNA in Escherichia coli; Liang ST et al.; To examine the previously proposed retroregulation model of spc mRNA degradation, two strains of Escherichia coli B/r were used; one has wild-type spc and lac operons and the other has a lac operon deletion, a wild-type spc operon, and a Pspc-rplN-lacZ fusion operon lacking the normal control sites of the spc operon (rplN is the first gene in the spc operon of ribosomal proteins) . The decay of rplN mRNA and of lacZ mRNA in these strains was determined during exponential growth at different rates and after transcript initiation was inhibited by the antibiotic rifampicin . Functional decay of lacZ mRNA was monitored by measurements of beta-galactosidase activity and chemical decay was monitored using probes complementary to rplN, rplX, and to the 5' and 3'-terminal sections of lacZ . Analysis of the data was based on the assumption that the decay involves an endonucleolytic cleavage that functionally inactivates the mRNA and that this is followed by exonucleolytic degradation of the cleavage products . The major conclusions were: (1) During exponential growth, lacZ mRNA of the lac operon was translated about twice as frequently as lacZ mRNA of the spc-lac fusion, and both kinds of lacZ mRNA were translated at an elevated rate in the presence of rifampicin . (2) For lacZ mRNA from the lac operon, the endonuclease inactivation reaction was not affected by rifampicin, but the exonuclease reaction was inhibited . (3) The decay of rplN mRNA from the spc operon was accelerated in the presence of rifampicin; the average life was estimated to be six minutes during exponential growth in LB medium, and 2.8 minutes in the presence of rifampicin . (4) The decay of the rplN section of mRNA from the spc-lac operon fusion was coupled to the decay of the downstream lacZ mRNA section and was strongly inhibited (i.e . partially blocked) in the presence of rifampicin . These results show that the decay of spc mRNA differs in some important aspects from the decay of lac mRNA and support the retroregulation model . Moreover, the results indicate that rifampicin can have a significant and selective impact on the kinetics of both mRNA translation and decay .

Am J Vet Res, 1999 May, 60(5), 603 - 8
Health and growth performance of barrows reared in all-in/all-out or continuous flow facilities with or without a chlortetracycline feed additive; Ice AD et al.; OBJECTIVE: To compare health and growth performance in barrows reared in all-in/all-out (AIAO) or continuous flow (CF) management systems . ANIMALS: 400 barrows . PROCEDURE: Barrows (approx 2 months old) were allotted to 4 replications (100 barrows each); barrows were housed in AIAO or CF rooms (10 pens/room), and 50 pigs/replicate received chlortetracycline (CTC, 110 mg/kg of feed) . Barrows from each pen were slaughtered at 3, 4, 5, and 6 months old . RESULTS: Barrows in the AIAO room had greater total daily gain (TDG) and lean daily gain (LDG) than did barrows in the CF room . Addition of CTC did not improve TDG or LDG in either environment . Barrows in the AIAO room reached body weight of 104.5 kg in 169.7 days, compared with 177.3 days for barrows in the CF room . Feed-to-gain ratio was not affected by management or CTC . Lungs from barrows reared in AIAO facilities had a lower percentage of lesions than did lungs of barrows reared in CF facilities (1.74% vs 9.52%) . Addition of CTC did not affect prevalence and extent of lung lesions . Extent of lung lesions was positively correlated with change in serum optical density (OD) to Mycoplasma hyopneumoniae (r = 0.35), but not with change in serum OD to Actinobacillus pleuropneumoniae . Lean growth and serum OD to M . hyopneumoniae and A . pleuropneumoniae were not correlated . CONCLUSIONS: Health and growth performance were better for barrows in an AIAO facility, compared with a CF facility, but addition of CTC to feed failed to enhance health or performance of barrows in either facility.

Ophthalmology, 1999 May, 106(5), 982 - 6
Conjunctival prolapse: a simple and effective treatment; Liu D; OBJECTIVE: To describe a simple and noninvasive technique to manage conjunctival prolapse and to report its efficacy . DESIGN: Noncomparative, retrospective case series . PARTICIPANTS: Ten consecutive patients encountered over a span of 13 years developed postoperative conjunctival prolapse as a complication from various ocular and orbital procedures . INTERVENTION: The prolapsed tissue is tucked back to its proper position with the aid of jeweler's forceps and a strip of gauze saturated with petroleum jelly and antibiotic ointment; thereafter, a double patch is applied to the closed eyelids . MAIN OUTCOME MEASURES: Successful resolution is usually attained within 48 hours . RESULTS: The technique is easy, efficient, and effective . All ten patients experienced no further complications after resolution . CONCLUSION: Clinicians should consider adopting this noninvasive technique.

Neurosci Lett, 1999 Apr 16, 265(2), 71 - 4
Dizocilpine attenuates streptomycin-induced vestibulotoxicity in rats; Basile AS et al.; NMDA receptor mediated excitotoxicity contributes substantially to aminoglycoside antibiotic-induced cochlear damage . Since vestibular as well as cochlear hair cells have glutamatergic synapses, aminoglycoside-induced vestibulotoxicity may also have an excitotoxic component . This hypothesis was tested by examining the effects of the uncompetitive NMDA receptor antagonist dizocilpine on streptomycin-induced vestibulotoxicity . Streptomycin-treated rats exhibited almost complete destruction of sensory hair cells in the crista ampullaris, vestibular impairment in the drop test, and hyperkinesia . Concurrent treatment with dizocilpine not only rescued a substantial population of sensory hair cells in the cristae, but prevented the attendant hyperkinesis and vestibular impairments . These results indicate that excitotoxic mechanisms contribute to aminoglycoside-induced vestibulotoxicity and that NMDA antagonists may be useful in attenuating aminoglycoside ototoxicity.

Anticancer Drugs, 1999 Mar, 10(3), 295 - 302
Comparative activity of the cyclopropylpyrroloindole compounds adozelesin, bizelesin and carzelesin in a human tumor colony-forming assay; Hidalgo M et al.; Adozelesin, bizelesin and carzelesin are synthetic cyclopropylpyrroloindole (CPI) analogs, a class of potent antineoplastic agents modeled on the antitumor antibiotic CC-1065, that specifically bind to the minor groove of DNA and preferentially alkylate AT-rich regions . These compounds were evaluated against fresh human tumors in a human tumor colony-forming assay (HTCFA) to assess and to compare their relative antitumor spectra, concentration-response relationships and schedule-dependence . Human tumor colony-forming units were treated with adozelesin and bizelesin at concentrations of 0.02, 0.1 and 0.5 ng/ml as a continuous exposure for 14 days, and to 0.2, 1.0 and 5.0 ng/ml as a 1 h exposure . Carzelesin concentrations were 0.04, 0.2 and 1 ng/ml as a continuous exposure, and 0.6, 3.0 and 15.0 ng/ml as a 1 h exposure . A response was scored if there was 50% or less colony survival . The three analogs had similar antitumor activity against colon carcinoma, kidney carcinoma and melanoma colony-forming units . Adozelesin also displayed activity against both breast and non-small cell lung carcinoma colony-forming units, and carzelesin was active against ovarian carcinoma colony-forming units . Significantly positive concentration-response relationships were apparent with all three agents . Responses increased from below 15% at the lowest concentration to above 45% at the highest concentration for the three drugs on all schedules (p < 0.01) . At the highest concentration, the overall response rate was significantly higher (p < 0.01) with carzelesin on the continuous schedule (71%) compared to the 1 h schedule (46%) . However, overall response rates for adozelesin and bizelesin were similar on both schedules (1 h/continuous: adozelesin, 67/58%; bizelesin, 49/44%), indicating that adozelesin and bizelesin are less schedule dependent than carzelesin in the HTCFA . These results demonstrate that the CPIs have broad-spectrum activity against human tumor colony-forming units in the HTCFA at very low concentrations, as well as differences with regard to schedule dependence which may help guide the optimal clinical development of these agents.

Drug Discov Today, 1999 Apr, 4(4), 163 - 172
Selective inhibitors of the osteoclast vacuolar proton ATPase as novel bone antiresorptive agents; Farina C et al.; The proton ATPase located on the apical membrane of the osteoclast is essential to the bone resorption process . This proton pump is, therefore, an attractive molecular target for the design of novel inhibitors of bone resorption, and potentially useful for the treatment of osteoporosis and related metabolic diseases of bone . Recently, several inhibitors with different degrees of selectivity for the osteoclast V-ATPase have been reported . In particular, systematic chemical modifications of the macrolide antibiotic bafilomycin A1 have identified the minimal structural requirements for activity and allowed the design of simplified analogues that demonstrate high potency and selectivity for the osteoclast enzyme.

Chem Biol, 1999 May, 6(5), 277 - 86
Calories from carbohydrates: energetic contribution of the carbohydrate moiety of rebeccamycin to DNA binding and the effect of its orientation on topoisomerase I inhibition; Bailly C et al.; BACKGROUND: Only a few antitumor drugs inhibit the DNA breakage-reunion reaction catalyzed by topoisomerase . One is the camptothecin derivative topotecan that has recently been used clinically . Others are the glycosylated antibiotic rebeccamycin and its synthetic analog NB-506, which is presently in phase I of clinical trials . Unlike the camptothecins, rebeccamycin-type compounds bind to DNA . We set out to elucidate the molecular basis of their interaction with duplex DNA, with particular emphasis on the role of the carbohydrate residue . RESULTS: We compared the DNA-binding and topoisomerase-I-inhibition activities of two isomers of rebeccamycin that contain a galactose residue attached to the indolocarbazole chromophore via an alpha (axial) or a beta (equatorial) glycosidic linkage . The modification of the stereochemistry of the chromophore-sugar linkage results in a marked change of the DNA-binding and topoisomerase-I- poisoning activities . The inverted configuration at the C-1' of the carbohydrate residue abolishes intercalative binding of the drug to DNA thereby drastically reducing the binding affinity . Consequently, the alpha isomer has lost the capacity to induce topoisomerase-I-mediated cleavage of DNA . Comparison with the aglycone allowed us to determine the energetic contribution of the sugar residue . CONCLUSIONS: The optimal interaction of rebeccamycin analogs with DNA is controlled to a large extent by the stereochemistry of the sugar residue . The results clarify the role of carbohydrates in stereospecific drug-DNA interactions and provide valuable information for the rational design of new rebeccamycin-type antitumor agents.

Chem Biol, 1999 May, 6(5), 287 - 92
Impact of thioesterase activity on tylosin biosynthesis in Streptomyces fradiae; Butler AR et al.; BACKGROUND: The polyketide lactone, tylactone, is produced in Streptomyces fradiae by the TylG complex of five multifunctional proteins . As with other type I polyketide synthases, the enzyme catalysing the final elongation step (TylGV) possesses an integral thioesterase domain that is believed to be responsible for chain termination and ring closure to form tylactone, which is then glycosylated to yield tylosin . In common with other macrolide producers, S . fradiae also possesses an additional thioesterase gene (orf5) located within the cluster of antibiotic biosynthetic genes . The function of the Orf5 protein is addressed here . RESULTS: Disruption of orf5 reduced antibiotic accumulation in S . fradiae by at least 85% . Under such circumstances, the strain accumulated desmycosin (demycarosyl-tylosin) due to a downstream polar effect on the expression of orf6, which encodes a mycarose biosynthetic enzyme . High levels of desmycosin production were restored in the disrupted strain by complementation with intact orf5, or with the corresponding thioesterase gene, nbmB, from S . narbonensis, but not with DNA encoding the integral thioesterase domain of TylGV . CONCLUSIONS: Polyketide metabolism in S . fradiae is strongly dependent on the thioesterase activity encoded by orf5 (tylO) . It is proposed that the TylG complex might operate with a significant error frequency and be prone to blockage with aberrant polyketides . A putative editing activity associated with TylO might be essential to unblock the polyketide synthase complex and thereby promote antibiotic accumulation.

J Bacteriol, 1999 May, 181(10), 3025 - 32
Phosphate control of oxytetracycline production by Streptomyces rimosus is at the level of transcription from promoters overlapped by tandem repeats similar to those of the DNA-binding sites of the OmpR family; McDowall KJ et al.; Physiological studies have shown that Streptomyces rimosus produces the polyketide antibiotic oxytetracycline abundantly when its mycelial growth is limited by phosphate starvation . We show here that transcripts originating from the promoter for one of the biosynthetic genes, otcC (encoding anhydrotetracycline oxygenase), and from a promoter for the divergent otcX genes peak in abundance at the onset of antibiotic production induced by phosphate starvation, indicating that the synthesis of oxytetracycline is controlled, at least in part, at the level of transcription . Furthermore, analysis of the sequences of the promoters for otcC, otcX, and the polyketide synthase (otcY) genes revealed tandem repeats having significant similarity to the DNA-binding sites of ActII-Orf4 and DnrI, which are Streptomyces antibiotic regulatory proteins (SARPs) related to the OmpR family of transcription activators . Together, the above results suggest that oxytetracycline production by S . rimosus requires a SARP-like transcription factor that is either produced or activated or both under conditions of low phosphate concentrations . We also provide evidence consistent with the otrA resistance gene being cotranscribed with otcC as part of a polycistronic message, suggesting a simple mechanism of coordinate regulation which ensures that resistance to the antibiotic increases in proportion to production.

Eur J Gastroenterol Hepatol, 1999 Apr, 11(4), 459 - 61
Vasculitic small bowel perforation masquerading as spontaneous bacterial peritonitis in a patient with decompensated liver disease; Verma S et al.; We report on a young patient with decompensated alcohol-induced liver disease (Child-Pugh score C) who presented with clinical, biochemical and radiological evidence suggestive of spontaneous bacterial peritonitis . She was however subsequently found to have multiple small bowel perforations, which were diagnosed only at laparotomy . The histology of the bowel showed evidence of vasculitis . This case illustrates two important points . Firstly, even if a patient has all the prerequisites to develop spontaneous bacterial peritonitis, a secondary cause of peritonitis (eg . bowel perforation or intra-abdominal abscess) must always be considered as a differential diagnosis and a repeat ascitic tap is mandatory after 48 h of antibiotic therapy to confirm a decrease in the white cell count . Secondly, it shows the rare co-existence of alcoholic liver disease and vasculitis.

Oncogene, 1999 Mar 25, 18(12), 2157 - 62
Suppression of Ras-mediated NIH3T3 transformation by p19ARF does not involve alterations of cell growth properties; Calabro V et al.; The INK4a gene, one of the most frequently disrupted loci in human cancer, encodes two unrelated proteins, p16INK4a and p19ARF, that both block cell proliferation . p16INK4a is a component of the Rb regulatory pathway, while p19ARF has been functionally related to p53 . Moreover, p16INK4a is inactivated in many human tumors, while it has been very recently reported that p19ARF null mice develop tumors early in life . We show here that p19ARF is able to inhibit the formation of G418-resistant colonies when transfected into human and mouse cell lines expressing wild-type p53, regardless of p16 status . Moreover its amino terminal domain encoded by exon 1beta is still sufficient to obtain the same effect . We have analysed the ability of p19ARF to interfere with Ras-mediated cellular transformation in the NIH3T3 cell line . Cotransfection of p19ARF together with activated ras potently inhibited the formation of transformed foci in a dose-dependent manner . We have also isolated stable NIH3T3 transfectants expressing p19ARF and we have measured their growth properties as well as their efficiency of transformation by activated ras . Our results suggest that p19ARF can interfere with oncogene-mediated transformation, without significantly affecting NIH3T3 cell growth, at least at the levels of expression achieved in these experiments.

Schweiz Med Wochenschr, 1999 Apr 10, 129(14), 563 - 9
{Pneumonia: what's new?}; Tauber MG; Pneumonia continues to be one of the most important infectious diseases which often leads to hospital admissions and is occasionally fatal . The spectrum of causative organisms, their sensitivity pattern to antibiotics, diagnostic tools, and available antibiotics are continually changing . Currently, the most disquieting trend is the increasing development of resistance to commonly used antibiotics by the pneumococcus . Although this trend has thus far been observed primarily in other countries, it will most likely not spare Switzerland . Rational empiric therapy must include careful clinical assessment of the patient, knowledge of the spectrum of organisms locally causing pneumonias, including their resistance patterns, as well as a prognostic assessment of the patient . Using these factors, possible antibiotic schemes for empiric therapy of community-acquired pneumonia are reviewed.

Schweiz Med Wochenschr, 1999 Apr 10, 129(14), 556 - 62
{Parapneumonic pleural effusion, pleural empyema: medical and surgical aspects}; Gugger M et al.; The following are essential for prophylaxis and treatment of empyema: antibiotic therapy for pneumonia, based on susceptibility results; early detection of parapneumonic effusions (decubitus radiograph, sonography); immediate diagnostic thoracocentesis if a parapneumonic effusion is large, increasing despite antibiotic therapy, if it is associated with clinical deterioration or if empyema is suspected; assessment of the stage of parapneumonic effusion or empyema (clinical signs, sonography, CT, laboratory parameters); immediate therapeutic thoracocentesis of frank empyema, in loculated empyema fibrinolytic agents may be used; early surgical intervention if conservative management fails; complete thoracoscopic decortication, if necessary open thoracotomy to assure complete reexpansion of the lung.

Ann Thorac Surg, 1999 Apr, 67(4), 966 - 71
Left ventricular mass reduction after aortic valve replacement: homografts, stentless and stented valves; Maselli D et al.; BACKGROUND: We studied the effect of four different types of prosthetic aortic valves on time course and extent of regression of left ventricular hypertrophy after aortic valve replacement for aortic stenosis . METHODS: Four groups of 10 patients each were randomly assigned to receive: (1) aortic homograft preserved in antibiotic solution at 4 degrees C, (2) Toronto stentless porcine valve, (3) Medtronic Freestyle stentless valve, or (4) Medtronic Intact aortic valve . The left ventricular mass index, effective orifice area index, and peak and mean transaortic gradients were measured by Doppler echocardiography before the operation and 8 months postoperatively . RESULTS: The hemodynamic performance indices were much better for the homograft and stentless valves than for the stented one . The absolute left ventricular mass index reduction was greater in the homograft group compared with the Intact (p = 0.0004) and Toronto (p = 0.007) groups . The extent of percent left ventricular mass index reduction was greater only in the homograft group versus Intact group (p = 0.005) . The multilinear regression analysis showed that the only predictors of a larger percentage of left ventricular mass index reduction were the homograft type, a higher valve size index, and a higher preoperative left ventricular mass index . CONCLUSIONS: When a stentless or homograft aortic valve was used instead of a stented valve to replace a stenotic aortic valve there was more complete or at least faster regression of left ventricular hypertrophy . The hemodynamic performance of stentless porcine valves was similar to that of aortic homografts, nevertheless the aortic homografts preserved in antibiotic solution offered a faster regression of left ventricular hypertrophy during the same period of time.

Kyobu Geka, 1999 May, 52(5), 408 - 11
{A case of successful reoperation for aortic root pseudoaneurysm ruptured into right ventricle after modified Bentall operation}; Asai T et al.; The patient was a 51-year-old man with Marfan syndrome who had simultaneously undergone modified Bentall operation (Carrel patch method) and coronary artery bypass grafting . Prosthetic valve endocarditis (PVE) occurred 19 months after the operation . PVE had thereafter been treated by antibiotic therapy for 3 months, but echocardiography revealed prosthetic valve detachment and aortic root pseudoaneurysm ruptured into the right ventricle which appeared to have been caused by PVE . At reoperation there were no laboratory or intraoperative findings indicative of ongoing inflammation or infection . The composite graft, therefore, didn't require replacing, and it was possible to simply re-suture the composite graft and directly close the tear . The postoperative course has been uneventful with no further evidence of endocarditis.

Kurume Med J, 1999, 46(1), 87 - 90
Aspergillus osteomyelitis in a child who has p67-phox-deficient chronic granulomatous disease; Tsumura N et al.; Here we describe Aspergillus osteomyelitis of the tibia in a 9-year-old boy who has an autosomal recessive form of chronic granulomatous disease (CGD) . The patient showed a p67-phagocyte oxidase (phox) deficiency, which is rare type of CGD in Japan . The initial treatment which consisted of surgical debridement and antibiotic therapy with amphotericin B (AMPH), did not control the infection . Aspergillus fumigatus (A . fumigatus) pure isolated from drainage fluid and necrotic bone tissue demonstrated less susceptible to antifungal agents, including AMPH, fluconazole and flucytosine . Recombinant interferon gamma was then administrated, and it was effective in controlling the course of severe invasive aspergillosis . This report indicates the use of interferon gamma might be helpful in control for Aspergillus osteomyelitis of the tibia in a child with CGD demonstrated p67-phox deficiency refractory to conventional therapy with AMPH.

Semin Hematol, 1999 Apr, 36(2), 139 - 47
Mucosa-associated lymphoid tissue lymphoma; Isaacson PG; A distinctive type of low-grade extranodal lymphoma recapitulates the cytomorphologic features of mucosa-associated lymphoid tissue (MALT) . Typically, these MALT lymphomas arise from sites normally devoid of lymphoid tissue, but are preceded by chronic inflammatory, usually autoimmune, disorders that result in the accumulation of lymphoid tissue . The stomach is the most common site of MALT lymphoma, which arises from lymphoid tissue acquired as the result of Helicobacter pylori infection . The indolent clinical behavior of gastric MALT lymphoma coupled with certain histologic features suggests that its growth is subject to immunologic stimuli, and the role of H pylori in this respect has been examined in detail . In vitro experiments have shown that the growth of lymphoma cells is stimulated by contact with T cells, which, in turn, show strain specific responses to heat-killed H pylori . Clinically, approximately 70% of cases of stage IE gastric MALT lymphoma regress following eradication of H pylori with antibiotics . Large, deeply invasive tumors and those that have undergone high-grade transformation typically do not respond to antibiotic therapy . Other common sites of MALT lymphoma include the salivary glands, lung, and ocular adnexa . The clinicopathologic features of these lymphomas are remarkably similar to gastric MALT lymphoma, which suggests that they, too, may be antigen-driven.

Curr Opin Rheumatol, 1999 Mar, 11(2), 151 - 7
Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain; Borenstein DG; Low back pain continues to affect a significant proportion of the younger, working population between 35 and 45 years of age . An important study has correlated macroscopic and microscopic intervertebral disc alterations starting in the second decade of life with oxidative stress manifested by the presence of N-(carboxylmethyl)lysine . Job satisfaction remains a strong predictive factor for the identification of individuals with acute back pain who will develop chronic pain . Patients with pyogenic vertebral osteomyelitis may have an increase in their erythrocyte sedimentation rate during the first 2 weeks of antibiotic therapy without requiring surgical intervention . Magnetic resonance imaging enhancement of migrated disc fragments identifies individuals who are likely to resolve sciatica without surgical intervention . As many as 25% of individuals with low back pain are symptomatic at 12 months, in contradistinction to the dictum of resolution of pain in 2 months . Nonsteroidal anti-inflammatory drugs and muscle relaxants are a very effective combination for the effective treatment of acute low back pain . A majority of chiropractic manipulations are performed for inappropriate indications.

Am J Gastroenterol, 1999 May, 94(5), 1218 - 23
Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication of Helicobacter pylori infection; McCarthy CJ et al.; OBJECTIVE: Helicobacter pylori (H . pylori) causes chronic gastritis . The inducible prostaglandin synthetase cyclooxygenase 2 (COX-2) plays an important role in inflammatory conditions . We hypothesized that H . pylori-associated chronic gastritis would express COX-2 protein . Our aim was to evaluate the effect of eradication of H . pylori infection on COX-2 expression in the antral mucosa of patients before and after antibiotic therapy . METHODS: Tissues were obtained from patients with non-ulcer dyspepia undergoing H . pylori eradication . Ten patients with proven H . pylori infection and subsequent successful eradication were studied . Three biopsies of antral mucosa were evaluated before and after H . pylori eradication . The amount of acute and chronic inflammation was quantitated . Immunohistochemical staining for COX-2 was expressed as a percentage of the total number of cells and correlated with the degree of chronic inflammation . RESULTS: Specific immunostaining for COX-2 was observed in antral mucosa of patients infected with H . pylori . Patchy cytoplasmic staining was seen in surface epithelial cells and strong cytoplasmic staining for COX-2 was seen in parietal cells . Spotty cytoplasmic staining for COX-2 was also seen in lamina propria plasma cells, as well as there being macrophages present in the germinal centers of lymphoid aggregates . COX-2 expression could be detected both before and after eradication of H . pylori . The mean percentage of cells staining for COX-2 was significantly higher in H . pylori-infected mucosa, compared with mucosa after successful H . pylori eradication (33.4% +/- 5.4 vs 18.9% +/- 3.3, p = 0.038) . COX-2 immunostaining correlated best with the chronic inflammation score (r2 = 0.78, p < 0.001) . There was a strong correlation for those subjects who were H . pylori infected, as well as for those who had successful H . pylori eradication . CONCLUSIONS: H . pylori associated acute and chronic antral inflammation was associated with immunohistochemical detection of COX-2 protein in epithelial cells, in addition to associated mononuclear cells and parietal cells . Expression was reduced, but not eliminated, in the epithelium after successful eradication of H . pylori . Despite the reduction in COX-2 expression after H . pylori eradication, expression of COX-2 in epithelial cells remained and strongly correlated with the extent of the chronic inflammatory cell infiltrate . The clinical implications of H . pylori-associated induction of COX-2 expression for patients on selective COX-2 inhibitors, in addition to the role of COX-2 in gastric carcinogenesis, deserve further study.

J Virol, 1999 Jun, 73(6), 5214 - 9
Epstein-barr virus (EBV) nuclear protein 2-induced disruption of EBV latency in the Burkitt's lymphoma cell line Akata: analysis by tetracycline-regulated expression; Fujiwara S et al.; The Burkitt's lymphoma (BL) cell line Akata retains the latency I program of Epstein-Barr virus (EBV) gene expression and cross-linking of its surface immunoglobulin G (IgG) by antibodies results in activation of viral replication . When EBV nuclear antigen 2 (EBNA2) was artificially expressed by a constitutive expression vector, the Cp EBNA promoter remained inactive and accordingly the latency III program was not induced . In contrast, expression of LMP2A and activity of the Fp lytic promoter were activated . Consistent with this Fp activity, the rate of spontaneous activation of the EBV replicative cycle was increased significantly, suggesting the possibility that EBNA2 can induce EBV replication . The efficiency of anti-IgG-induced activation of the viral replication was reduced in Akata cells expressing EBNA2 . To obtain more direct evidence for EBNA2-induced activation of the EBV replicative cycle, this protein was next expressed by a tetracycline-regulated expression system . EBNA2 was undetectable with low doses (<0.5 microgram/ml) of tetracycline, while its expression was rapidly induced after removal of the antibiotic . This induced expression of EBNA2 was immediately followed by expression of EBV replicative cycle proteins in up to 50% of the cells, as shown by indirect immunofluorescence and immunoblot analysis . These results suggest an unexpected potential of EBNA2 to disrupt EBV latency and to activate viral replication.

BJU Int, 1999 Apr, 83(6), 703 - 8
Brefeldin A-induced apoptosis in prostatic cancer DU-145 cells: a possible p53-independent death pathway; Chapman JR et al.; OBJECTIVE: To investigate the growth inhibitory mechanism of brefeldin A (BFA), an antiviral antibiotic, in androgen-independent prostatic cancer DU-145 cells . MATERIALS AND METHODS: The inhibitory effects of BFA (30 ng/mL) on cell growth were monitored by cell counting and viability tests after specified exposures . Flow cytometry and western immunoblot analysis were performed to examine the effects of BFA on the cell cycle and on specific growth regulators . The possible induction of apoptosis by BFA was further assessed by in situ hybridization (ISH) assay and by qualitative DNA analysis using agarose-gel electrophoresis . RESULTS: Cell growth was completely inhibited with BFA (30 ng/mL), accompanied by 40-50% cell death . Cell cycle analysis revealed that this growth inhibition coincided with an 85% reduction in the S-phase cell population . Western blots showed that the expression of cell cycle-dependent kinases (cdk2 and cdk4), cyclin D1 and p53 was significantly reduced, while WAF1 was increased, after BFA treatment . Apoptosis was confirmed by both the ISH assay, which showed the characteristic brownish staining of BFA-treated cells, and by DNA analysis, which revealed the internucleosomal DNA ladder . CONCLUSION: BFA-induced growth inhibition in DU-145 cells is primarily due to the modulation of specific G1 cell-cycle regulators, blocking the G1-S phase progression . Such a growth arrest ultimately results in apoptosis, presumably through a p53-independent pathway.

Am Surg, 1999 May, 65(5), 439 - 43
Wound management in perforated appendicitis; Lemieur TP et al.; Open wound management after perforated appendicitis was common practice but, recently, primary closure has been advocated to reduce costs and morbidity . Hospital records from 319 adults who underwent appendectomy from 1993 to 1996 were reviewed to identify surgical wound infections (SWIs) and examine risk factors . Information about age, length of stay (LOS), operative time, white blood cell count, and antibiotic administration were obtained . Perforation was either noted at operation or identified microscopically by the pathologist . If primary wound closure was performed, patients with acute appendicitis and perforation had a 4-fold higher readmission rate, a 5-fold increase in SWI, and twice the LOS compared with patients with acute appendicitis without perforation . Patients with grossly perforated acute appendicitis had no difference in LOS if the wound was treated open or closed primarily . No patient with microscopic perforation and primary wound closure developed SWI . Primary wound closure after acute appendicitis was safe in the absence of clinical perforation . In the presence of clinical appendiceal perforation the wound should be left open.

Q J Nucl Med, 1999 Mar, 43(1), 93 - 9
Nuclear medicine imaging of endocarditis; Ivancevic V et al.; Infective endocarditis is a serious disease which requires early diagnosis and adequate therapy . Echocardiography plays a key role in diagnosis and follow-up . Subacute infective endocarditis, however, is often difficult to prove echocardiographically due to its more subtle morphological changes . Also, echocardiography cannot reliably differentiate florid vegetations from residual structural changes of the affected valves in cured patients . Therefore, scintigraphy of infection and inflammation, a functional imaging procedure, has been investigated as a complementary tool in diagnosis and follow-up of infective endocarditis . So far, results obtained with Gallium-67 scintigraphy are not convincing, although an improvement by using modern acquisition techniques seems possible . Scintigraphy with Indium-111 labelled leukocytes has an unacceptably low sensitivity, which is probably due to the small number of cells involved and unfavourable imaging characteristics of 111In-Technetium-99m labelled leukocytes have been investigated in few patients, so final judgement is not yet possible . SPECT imaging might enhance the detectability of diseased heart valves . Immunoscintigraphy with the 99mTc labelled antigranulocyte antibody in SPECT technique is complementary to echocardiography and seems to assess the floridity of the underlying inflammatory process . The combined use of both imaging modalities allows detection of virtually all cases of subacute infective endocarditis . SPECT immunoscintigraphy with the antigranulocyte antibody seems useful in doubtful cases of infective endocarditis, especially, if echocardiography is non-diagnostic and valve pathology pre-existing . The method may be used for follow-up and monitoring antibiotic therapy.

J Spinal Disord, 1999 Apr, 12(2), 89 - 93
Spinal epidural abscess: a review of epidemiology, diagnosis, and treatment; Sampath P et al.; Despite advances in neuroimaging and neurosurgical treatment, spinal epidural abscess (SEA) remains a challenging problem for the practicing physician . Early diagnosis is often elusive, and treatment is delayed . The optimal management of SEA is not clearly defined, and morbidity and mortality remain significant . In this review article, we discuss contemporary issues surrounding SEA . In addition, we shed light on the epidemiology of this potentially devastating disease and outline current diagnostic and therapeutic guidelines . We find the frequency of diagnosis of SEA is increasing . To prevent serious morbidity and mortality, early diagnosis and prompt treatment are essential . Patients who are at high risk for developing such abscesses should have an immediate magnetic resonance scan with contrast enhancement . Surgical drainage and prolonged antibiotic use are the cornerstones of treatment, although selected patients may be treated nonsurgically with very vigilant medical follow-up.

Acta Paediatr, 1999 Mar, 88(3), 284 - 9
Serologic response to Bartonella henselae in patients with cat scratch disease and in sick and healthy children; Not T et al.; Indirect fluorescent antibody assay (IFA) is the most reliable test for detecting antibody to Bartonella henselae in the diagnosis of cat scratch disease (CSD) . Recently, an ELISA test has been proposed, but conflicting results are reported . We compared IgG-IFA and IgG-IgM ELISA methods in CSD patients and in healthy children . We also tested ELISA specificity in a large group of healthy controls and in children with lymphoma-associated lymphadenopathy and with pyogenic lymphadenitis . The ELISA procedure was positive in 69/78 patients with CSD (sensitivity 89.6%), in 5/100 healthy children (specificity 95%), in 2/51 patients with non-Hodgkin's lymphoma or pyogenic lymphadenitis (specificity 96%) and in 27/296 blood donors (specificity 91.6%) . In 34 patients with CSD, ELISA IgM and IgG responses decreased significantly between time of diagnosis of the disease and recovery . We found significantly higher IgG-ELISA titres in cat-owners, whether blood donors or healthy children, than in non-cat-owners . The IgG-IFA test gave positive results in 69/78 patients with CSD (sensitivity 89.6%) and in 5/62 healthy controls (specificity 92.5%) . The ELISA method is a cheap, sensitive method for determining antibody response to Bartonella henselae infection and is also important for evaluating the clinical course of the disease and the efficacy of antibiotic therapy . The high specificity of ELISA in patients with non-Hodgkin's lymphoma will help the clinician to exclude a potentially life-threatening disease associated with lymphadenopathy.

Jt Comm J Qual Improv, 1999 Apr, 25(4), 182 - 90
Improving the care of patients with community-acquired pneumonia: a multihospital collaborative QI project; Metersky ML et al.; BACKGROUND: Performance of several processes of care was measured in eight acute care hospitals in Connecticut which provided inpatient treatment to 713 elderly patients with community-acquired pneumonia (CAP) . BASELINE DATA ABSTRACTION AND FEEDBACK: Chart review feedback was provided, and the hospitals were requested to design their own quality improvement (QI) interventions, after which reexamination of process of care performance was conducted . HOSPITAL QI INTERVENTIONS: Six of the eight hospitals had submitted QI plans . The quality indicators dealing with timeliness of antibiotic delivery were specifically addressed by five hospitals . However, each hospital also picked one or two other processes of care for intervention . RESULTS: The mean time to antibiotic administration decreased from 5.5 hours (+/- 0.2) to 4.7 hours (+/- 0.3; p < 0.0001), and the percentage of patients who received antibiotics within four hours increased from 41.5% to 61.8% (p < 0.0001) . DISCUSSION: This project called for obtaining buy-in from both the clinician and administrative representatives of each hospital early in the process . In this way, the targeted processes of care were likely to have relevance for each of the participating hospitals . Education of practicing physicians and other health professionals, as the method chosen by each hospital to address delays in antibiotic administration, appears to have been successful in this project as part of a multifaceted intervention . The project also helped establish a collegial environment that has served as the basis for more ambitious pneumonia QI projects . SUMMARY AND CONCLUSIONS: Widespread improvements in process of care performance can result from hospitals' participation in Quality Improvement Organization collaboration.

EMBO J, 1999 May 4, 18(9), 2500 - 10
Non-transcriptional action of oestradiol and progestin triggers DNA synthesis; Castoria G et al.; The recent findings that oestradiol and progestins activate the Src/Ras/Erks signalling pathway raise the question of the role of this stimulation . Microinjection experiments of human mammary cancer-derived cells (MCF-7 and T47D) with cDNA of catalytically inactive Src or anti-Ras antibody prove that Src and Ras are required for oestradiol and progestin-dependent progression of cells through the cell cycle . The antitumoral ansamycin antibiotic, geldanamycin, disrupts the steroid-induced Ras-Raf-1 association and prevents Raf-1 activation and steroid-induced DNA synthesis . Furthermore, the selective MEK 1 inhibitor, PD 98059, inhibits oestradiol and progestin stimulation of Erk-2 and the steroid-dependent S-phase entry . The MDA-MB231 cells, which do not express oestradiol receptor, fail to respond to oestradiol in terms of Erk-2 activation and S-phase entry . Fibroblasts are made equally oestradiol-responsive in terms of DNA synthesis by transient transfection with either the wild-type or the transcriptionally inactive mutant oestradiol receptor (HE241G) . Co-transfection of catalytically inactive Src as well as treatment with PD98059 inhibit the oestradiol-dependent S-phase entry of fibroblasts expressing either the wild-type oestrogen receptor or its transcriptionally inactive mutant . The data presented support the view that non-transcriptional action of the two steroids plays a major role in cell cycle progression.

Rev Med Interne, 1999 Feb, 20(2), 121 - 7
{Secondary aortoduodenal fistulas: report of 7 cases}; Constans J et al.; PURPOSE: Aortoduodenal fistulas are the most frequent aortoenteric fistulas . They may be primary (occurring after aneurysms of the native aorta) or secondary (occurring after aortic prosthesis) . Aortoduodenal fistulas are a rare complication of aortic prostheses . They may be caused by prosthesis infection or due to inadequate prosthesis . METHODS: We report seven observations that emphasize issues pertaining to either diagnosis or therapy . RESULTS: The delay of occurrence is variable, with a mean of 3 years as reported in the literature . Clinical picture includes upper digestive tract hemorrhage, sometimes fever, abdominal pain or mass . Though difficult, diagnosis can be achieved through gastric endoscopy or CT-scan . Additional diagnostic procedures are often not useful and should not be numerous . Surgical procedures help guide the diagnosis and constitute the main part of the treatment with suture of the duodenum and vascular prosthesis . According to previous works, our observations including prolonged follow-up of the patients suggest that the best vascular treatment is extra-anatomic axillo-bifemoral bypass, while simple suture and prosthesis replacement lead to poor results . CONCLUSION: Mortality related to aortodigestive fistulas is high (five out of seven patients in the present study) and requires prevention, including more particularly delicate surgery and antibiotic therapy in case of any episode of infection . Aortoduodenal fistulas must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained fever.

J Immunol, 1999 May 1, 162(9), 5437 - 43
Multiple roles for IL-12 in a model of acute septic peritonitis; Steinhauser ML et al.; The present study addressed the role of IL-12 in a murine model of septic peritonitis, induced by cecal ligation and puncture (CLP) . Although CLP surgery induced IL-12 production at 6 and 24 h after surgery, IL-12 immunoneutralization was clearly deleterious in this model: 54% of CLP mice receiving preimmune serum survived, whereas mice administered IL-12 antisera prior to CLP experienced a 25% survival rate . IL-12 immunoneutralization not only led to increased mortality, but also appeared to promote a shift away from IL-12 and IFN-gamma, in favor of IL-10 . This cytokine shift corresponded to changes in bacterial load, as CLP mice receiving IL-12 antiserum yielded more CFUs from the peritoneal cavity at 24 h after CLP . To address the role of bacterial infection in IL-12 antiserum-induced mortality following CLP, antibiotics were administered for 4 days after surgery . Despite regular antibiotic administration, IL-12 immunoneutralization still reduced survival in CLP mice . Furthermore, histology of the ceca revealed that mice administered IL-12 antisera failed to show typical organization of the damaged cecum wall . Accordingly, Gram staining revealed bacteria within peritoneal fluids from these mice, while peritoneal fluids from CLP mice that received preimmune serum and antibiotics were free of bacteria . Altogether, these data suggested multiple important roles for IL-12 in the evolution of murine septic peritonitis.

Pharmacol Toxicol, 1999 Apr, 84(4), 147 - 53
Comparison of tobramycin nephrotoxicity in young adult and aged female rats; Peters-Volleberg GW et al.; A two week toxicity study was performed in rats to study the possible age-dependent toxicity of tobramycin, an aminoglycoside antibiotic with well known ototoxic and nephrotoxic properties in animals and man . Young adult female Wag/Rij rats aged 12 weeks (n = 10) and old female rats aged 23 to 26 months (n = 14) were treated subcutaneously with 0, 10, 40 or 160 mg tobramycin sulphate/kg/day . Clinical chemistry and urinalysis revealed significant changes in renal function in young adult rats mainly at 160 mg/kg, whereas in old rats significant changes were seen at 10, 40 and 160 mg/kg . Excretion of N-acetyl-beta-glucosaminidase, indicative for tubular dysfunction, was statistically significantly increased only in old animals at 160 mg/kg . Histopathology: At 40 mg/kg, tubular necrosis was increased in old animals and hyaline droplet formation in both age groups . At 160 mg/kg these lesions were increased in both age groups . For tubulonephrosis, interstitial nephritis and tubular regeneration, age-related differences were predominantly reflected in severity, for example, at 40 mg/kg, tubular regeneration in young animals was "moderate" in 7/10 and "marked" in 2/10, while in old animals the scores were 3/14 and 11/14, respectively . Secondary treatment-related lesions (in heart and adrenals) were also more increased in old animals . Chemistry and histopathology revealed the increased sensitivity to the toxic effects of tobramycin in old rats, which is important for the discussion of the most appropriate dosing regimen for aminoglycoside in humans . The once-daily dosing regimen for tobramycin should not be recommended for elderly, because high peak concentrations should be avoided to minimise nephrotoxicity.

Int J Urol, 1999 Feb, 6(2), 61 - 7
Effect of recombinant human granulocyte colony stimulating factor (lenograstim) on chemotherapy induced neutropenia in patients with urothelial cancer; Kotake T et al.; BACKGROUND: A multicenter cooperative study to evaluate clinical usefulness of recombinant human granulocyte colony stimulating factor (rG-CSF; lenograstim) in the treatment of neutropenia associated with cancer chemotherapy was conducted in patients with urothelial cancer . METHODS: Therapeutic responses were compared within each patient between the observation and study treatment phases . RESULTS: Treatment with rG-CSF raised the nadir of the neutrophil count (343 to 3015/mm3), reduced the duration of neutropenia (6.2 to 0.4 days) and hastened recovery from the neutropenic state (23.5 to 5.5 days) . Febrile neutropenia was encountered in 12 patients during the observation phase alone and in only one patient during the study treatment phase alone . The mean duration of febrile neutropenia was also shortened (0.39 to 0.12 days) . In addition, the duration of antibiotic therapy was significantly reduced during treatment . The percentage of patients completing the chemotherapeutic regimens of combination M-VAC therapy was markedly increased to 81.0% as a result of rG-CSF therapy compared with 44.8% in the observation phase . Adverse reactions were observed in four patients and abnormal laboratory values were found in nine patients . None of these adverse events was of a serious nature . CONCLUSIONS: These results indicate that rG-CSF is a useful drug for the treatment of neutropenia associated with chemotherapy in urothelial cancer.

Schweiz Med Wochenschr, 1999 Mar 20, 129(11), 441 - 5
Attitude to Helicobacter pylori infection among Swiss gastroenterologists; Binek J et al.; OBJECT: To assess the current attitude to Helicobacter pylori infection in Switzerland, since a review of the literature reveals few publications dealing with application of therapeutic recommendations . METHODS: The initial diagnostic methods, the indications for eradication therapy, the therapeutic regimen and its duration, together with eradication control, were indicated in questionnaires sent out to the members of the Swiss Society for Gastroenterology and Hepatology at the beginning of 1997 . RESULTS: Helicobacter pylori was diagnosed mainly with a rapid urease test and/or histology . Peptic ulcer disease (100%), mucosa associated lymphoid tissue (MALT) lymphoma (94.5%) and therapy-resistant dyspepsia (78.7%) were clear indications for Helicobacter pylori eradication . Only a minority eradicated Helicobacter pylori in all positive subjects . 7-day triple therapy (with proton pump inhibitors, a macrolide antibiotic and an imidazole derivative) is the preferred first line treatment . CONCLUSIONS: The eradication of Helicobacter pylori in ulcer disease is established practice . Non-ulcer dyspepsia remains a controversial but often used indication . Two antibiotics together with proton pump inhibitors constitute the mostly widely used eradication therapy.

Exp Physiol, 1999 Mar, 84(2), 275 - 84
H+-zwitterionic amino acid symport at the brush-border membrane of human intestinal epithelial (CACO-2) cells; Thwaites DT et al.; Transport of a number of dipolar amino acids (and the orally active antibiotic D-cycloserine) across the apical membrane of human intestinal epithelial (Caco-2) cell monolayers is mediated by a Na+-independent, pH-dependent transport mechanism . Relatively little is known about the mode of action of this transport system so to differentiate between pH dependence and proton coupling three experimental protocols were designed and tested . The results demonstrate, firstly, that it is the transapical pH gradient and its maintenance (rather than apical acidity alone) that is important in amino acid uptake . Secondly, Na+-independent uptake of seven dipolar amino acids (with pKa (-log of acid dissociation constant) values between 1 50 and 4 23) showed a similar dependence on apical pH (half-maximal uptake being observed at pH 5 99-6 20) . Thirdly, the pattern of pH-dependent amino acid ({beta}-alanine) uptake is similar irrespective of whether the cationic substrate concentration is varied or constant, demonstrating no relationship between uptake and concentration of the cationic form of the amino acid . These observations demonstrate that the transport mechanism is a H+-zwitterionic amino acid symporter and suggest that the presence of a H+ gradient at the apical surface of the human small intestine (in the form of the acid microclimate) may be important in driving nutrient absorption.

J Am Assoc Gynecol Laparosc, 1999 May, 6(2), 225 - 8
Conservative management of delayed suprapubic abscess after laparoscopic Burch colposuspension using nonabsorbable polypropylene mesh; Balaloski SP et al.; To our knowledge, abscess formation after laparoscopic Burch colposuspension using permanent surgical mesh has not been previously reported . In our patient a suprapubic abscess was identified 4 weeks after the procedure in which polypropylene mesh was used . Conservative management involving drainage under computerized tomographic guidance and antibiotic therapy resulted in complete resolution without necessitating removal of the mesh . (J Am Assoc Gynecol Laparosc 6(2):225-228, 1999)

Liver Transpl Surg, 1999 May, 5(3), 249 - 51
Disseminated Bartonella infection with granulomatous hepatitis in a liver transplant recipient; Humar A et al.; Disseminated infection with Bartonella spp with granulomatous hepatitis was diagnosed in a liver transplant recipient presenting with fever of unknown origin . Pathological findings on liver biopsy were atypical, with scant granulomas seen only after a second biopsy . The patient responded promptly to antibiotic therapy . Infections caused by Bartonella spp should be considered in transplant recipients with fever of unknown origin.

Scand J Infect Dis, 1998, 30(6), 620 - 1
Prolonged respiratory failure in chlamydia pneumoniae pneumonia; Machi T et al.; We describe a 65-year-old man, who had cardiomyopathy and developed acute respiratory failure requiring ventilator treatment . Acute pneumonia caused by Chlamydia pneumoniae was diagnosed based on PCR positivity of bronchoalveolar lavage . Gas exchange did not improve in response to appropriate antibiotic therapy, and the patient died.

APMIS, 1999 Feb, 107(2), 225 - 30
Hepatic actinomycosis . A case report; Andersen AB et al.; A case of hepatic actinomycosis contracted one year after removal of an intrauterine device during ongoing Actinomyces cervicitis is reported . During active disease, lymphocytes from the apparently fully immunocompetent patient were able to proliferate but not to produce the proinflammatory lymphokine gamma-interferon in response to Actinomyces antigen . This ability was only partly restored during antibiotic therapy.

FEMS Immunol Med Microbiol, 1999 Apr, 23(4), 283 - 8
Passive protective effect of egg-yolk antibodies against enterotoxigenic Escherichia coli K88+ infection in neonatal and early-weaned piglets; Marquardt RR et al.; The protective effects of egg-yolk antibodies obtained from hens immunized with fimbrial antigens from a local strain (Escherichia coli K88+ MB, Manitoba, Canada) of K88+ piliated enterotoxigenic E . coli (ETEC) were evaluated in 3- and 21-day-old piglets in which ETEC diarrhea was induced and also in early-weaned piglets in a commercial farm . The results demonstrated that the E . coli K88+ MB-induced diarrhea in 3-day-old piglets was cured 24 h after treating with egg-yolk antibodies while those treated with egg-yolk powder from conventional hens continued to have diarrhea and 62.5% of them died of severe diarrhea . For 21-day-old weaned piglets, those fed egg-yolk antibodies had transient diarrhea, positive body weight gains and 100% survival during the period of the experiment, whereas control piglets that were treated with placebo had severe diarrhea and dehydration and some died within 48 h after infection . In the field trial, the incidence and severity of diarrhea of 14-18-day-old weaned piglets fed egg-yolk antibodies were much lower than in those fed a commercial diet containing an antibiotic . These results indicate that the neonatal and early-weaned piglets that received the egg-yolk antibodies were protected against ETEC infection.

Clin Otolaryngol, 1999 Apr, 24(2), 126 - 9
Myringoplasty: a prospective audit study; Kotecha B et al.; Seventy-three surgeons participated in a prospective audit of myringoplasty . They returned data on 1070 individual patients . Up to 12 months follow-up information was obtained . The mean number of myringoplasties performed per consultant in 1 year (1995) was 14.7 (95% confidence intervals (CI) 12.1 17.2) . The main indication for performing the operation was to achieve an intact tympanic membrane . The mean graft take rate was 82.2% . When hearing improvement was the main indication for surgery it was improved in 67% . The use, or not, of an antibiotic had no significant influence on the graft take rate or the complication rate . Most complications reported were minor in nature.

Ear Nose Throat J, 1999 Apr, 78(4), 262 - 5, 268
A proposal for a staging system for hyperplastic rhinosinusitis based on the presence or absence of intranasal polyposis; Eichel BS; This study of 30 patients with hyperplastic rhinosinusitis reveals that the major determinant of the success or failure of conservative therapy is the presence or absence of intranasal polyposis . When polyposis is confirmed both clinically and radiographically, surgical intervention appears to be the rational way to handle most cases . When intranasal polyps are not present, an aggressive medical regimen is called for, one that includes a short-term, low-dose oral corticosteroid and an antibiotic, along with periodic radiographic assessment . Regardless of how much disease is seen on computed tomography, if it does not also detect intranasal polyps or masses, the potential for clearing with conservative therapy is extremely high.

Alaska Med, 1999 Jan-Mar, 41(1), 13 - 5
The effect of laser radiation on the metabolic processes of cellular membranes in pelvic inflammatory disease; Kattakhodjaeva MH et al.; The metabolic products of peroxide oxidation of cellular membrane lipids and the activity of the antioxidant enzyme superoxidismutase in blood plasma was determined in 68 patients with acute pelvic inflammatory disease and exacerbation of chronic pelvic inflammatory disease . The analyses were done before treatment, after routine antibiotic therapy, and after low energy laser radiation treatment . During acute inflammation and exacerbation of chronic inflammation, peroxide oxidation of cellular membrane lipids intensifies and antioxidant enzyme activity decreases . Helium-neon laser rays in addition to routine antibiotics appear to stabilize peroxide oxidation and normalize antioxidation enzyme activity more than antibiotics alone.

Can J Surg, 1999 Apr, 42(2), 145 - 8
Slipped capital femoral epiphysis after septic arthritis of the hip in an adolescent: report of a case; Marx RG et al.; Septic arthritis of the hip must be managed promptly to avoid the serious complications associated with the condition . In the case reported here, the diagnosis was delayed and was complicated by a slipped capital femoral epiphysis . The patient, an adolescent boy previously in good health, presented with a 2-week history of hip pain and systemic illness . Septic arthritis was diagnosed and was managed by incision and drainage and antibiotic therapy . Two weeks later he presented with a subcutaneous abscess and a slipped capital femoral epiphysis, which was pinned in situ . There was a 2.5-cm leg-length discrepancy . Avascular necrosis of the femoral head subsequently developed leaving the boy with a permanent disability.

Postgrad Med, 1999 Apr, 105(4), 177 - 80, 183-4, 187
When to suspect ischemic colitis . Why is this condition so often missed or misdiagnosed?
Alapati SV, Mihas AA.
Ischemic colitis is one of the most often seen disorders of the large intestine in the elderly . Common predisposing factors are atherosclerosis, shock, and congestive heart failure, but often, elderly patients have no obvious predisposing or precipitating factors . The typical clinical presentation is acute sudden abdominal pain and distention with bloody diarrhea . Common early radiographic signs are bowel-wall thickening with thumbprinting, and later, ulceration and strictures may be found . Endoscopy is valuable in revealing the sharp demarcation between viable and necrotic colonic mucosa that is a strong indicator of ischemia . Within 48 hours, most patients show favorable response to conservative measures consisting of intravenous hydration, bowel rest, antibiotic therapy, and correction of precipitating processes . Vasoconstricting drugs and corticosteroids are contraindicated . When surgical intervention is indicated, it usually consists of resection of the ischemic segment and exteriorization of the remaining ends of the bowel.

Kansenshogaku Zasshi, 1999 Mar, 73(3), 218 - 24
{Epidemiological characteristics and virulence factor of verotoxin-producing Eschericia coli O121:H19 isolated in Akita Prefecture in July 1997}; Yatsuyanagi J et al.; Epidemiological characteristics and virulence factors of VTEC O121:H19 strains isolated in July 1997 from a 15 year old female and a 20 year old male patient suffering from bloody diarrhea and severe abdominal pain were examined . The 2 VTEC O121:H19 isolates showed identical antibiotic susceptibility patterns, biochemical characteristics and plasmid profile while slight differences were observed in their Xba I and Not I PFGE patterns, suggesting that closely related 2 VTEC O121:H19 strains evoked the sporadic infectious cases in July 1997 . The 2 VTEC O121:H19 isolates, as well as VTEC O157:H7, possessed eaeA gene and a ca . 60 MDa plasmid which hybridised with CVD 419 probe and produced enterohemolysin . In addition, the VTEC O121:H19 isolates produced almost the same amount of VT-2 in vitro as VTEC O157:H7 did . These results suggested that VTEC O121:H19 possesed the virulence factor comparable to that of VTEC O157:H7 . Incidence, molecular epidemiology and infectious source of VTEC O121:H19 in this country have not been sufficiently understood . Antiserum for E . coli serogroup O121 should be manufactured to clarify the epidemiology of the highly virulent VTEC strain.

Spine, 1999 Apr 15, 24(8), 818 - 22
Conservative management of pyogenic osteomyelitis of the occipitocervical junction; Spies EH et al.; STUDY DESIGN: A report of three cases of pyogenic osteomyelitis of the occipitocervical junction . OBJECTIVE: To describe the conservative management of pyogenic osteomyelitis of the occipitocervical junction . SUMMARY OF BACKGROUND DATA: The therapeutic approach to inflammation of the upper cervical spine is controversial . METHODS: Pyogenic osteomyelitis of the occipitocervical junction is rare . In the orthopedic literature, only a few case reports with variable treatment methods are available . Three patients with pyogenic osteomyelitis of the occipitocervical junction were treated nonoperatively . Intravenous antibiotic therapy was begun after direct cultures or blood cultures were obtained . Early mobilization was accomplished by application of a halo vest . RESULTS: Two patients recovered by spontaneous fusion of the occipitocervical junction . Instability developed in the spine of one patient, but she refused further treatment . CONCLUSIONS: Diagnosis of osteomyelitis of the upper cervical spine is difficult . In cases with absence of neurologic symptoms or spinal abscess formation, treatment can be nonoperative.

Biochem Biophys Res Commun, 1999 Apr 29, 258(1), 29 - 31
Effect of the selection marker on the viability and plasmid stability of two human proteins with neurotrophic action expressed in Escherichia coli; Mari YM et al.; Most developed expression systems rely on the production of fusion proteins or the change of selection marker increasing genetic stability to avoid toxicity of heterologous proteins to Escherichia coli host cells . According to this, we analyzed the effect of the selection marker on the viability and plasmid stability of vectors pYMK5 and pYMK7 that codify neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) . We also analyzed the influence of two different lac promoter inducers on these parameters . We found that the addition of IPTG to culture medium produced a significant decrease of viability and plasmid stability for both expression vectors compared with values reached with lactose . There was no increase of both parameters when we changed the selection marker, so we can conclude that, in our case, a change of antibiotic does not solve the problem of low plasmid stability values .

Pediatr Int, 1999 Apr, 41(2), 218 - 22
Risk factors for the development of Escherichia coli O157:H7 associated with hemolytic uremic syndrome; Kawamura N et al.; Verotoxin-producing Escherichia coli (VTEC) O157:H7 is a major cause of hemorrhagic colitis that is often associated with the development of hemolytic uremic syndrome (HUS) . In July, 1996, a severe mass outbreak of VTEC O157 infection occurred in Sakai city, Osaka . The present study investigates the risk factors which may contribute to the development of HUS in the early stages of the VTEC O157 infection . There was no significant difference between HUS-developed and non-HUS-developed groups with respect to sex, age, rates of clinical manifestations, such as fever, abdominal pain and bloody stool, use of anti-diarrheal agents, anti-motility agents, and/or antibiotic agents, and serum sodium concentrations at the early stage of VTEC O157 infection . Thus, these factors did not appear to be risk factors associated with the development of HUS . In contrast, leukocyte counts and C-reactive protein levels in the early stage of VTEC O157 infection were significantly higher in the HUS-developed group (P < 0.001), suggesting that these are risk factors associated with the development of HUS.

Mol Pharmacol, 1999 May, 55(5), 841 - 6
Rifampicin is not an activator of the glucocorticoid receptor in A549 human alveolar cells; Jaffuel D et al.; It has recently been reported that rifampicin activates the glucocorticoid receptor and acts as an immunosuppressive drug . Because rifampicin constitutes an essential part of pulmonary tuberculosis therapy, we have examined whether it triggers glucocorticoid-like effects in alveolar cells . We have used reporter gene assays to measure the trans-activating and trans-repressing capacity of the glucocorticoid receptor after treating A549 human alveolar cells with rifampicin . The data show that rifampicin neither activated transcription from a promoter containing a glucocorticoid response element nor repressed the activity of activator protein 1 and nuclear factor kappaB, which are transcription factors involved in the immune response . In addition, rifampicin was also unable to inhibit the expression of an endogenous gene that contains activator protein 1 and nuclear factor kappaB response elements and encodes the proinflammatory cytokine RANTES (regulated upon activation normal T expressed and secreted protein) . Finally, nuclear translocation of the glucocorticoid receptor, which occurs after ligand binding, was not triggered by rifampicin . In contrast, the glucocorticoid dexamethasone scored positive in all corresponding control experiments . In conclusion, rifampicin is not an activator of the glucocorticoid receptor in A549 alveolar cells . Our results support the clinical observation that rifampicin is not an immunosuppressive drug and suggest that the current medical practice concerning this antibiotic should not be changed.

Asian Pac J Allergy Immunol, 1998 Dec, 16(4), 155 - 60
IL-1beta, IL-6 and TNF-alpha in synovial fluid of patients with non-gonococcal septic arthritis; Osiri M et al.; Interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are the main proinflammatory cytokines responsible for the inflammatory process and cartilage destruction of inflammatory arthropathies . The present study sequentially measured the concentrations of these cytokines and their proportions of detectable levels in the synovial fluid (SF) of 23 patients with non-gonococcal (GC) septic arthritis before and after treatment . Persistently high concentrations and proportions of IL-6 and TNF-alpha were found up to day 7 of treatment, while SF IL-1beta concentration declined significantly after day 7 (p = 0.036) . SF IL-1beta and TNF-alpha correlated with each other significantly and with SF WBC counts (p < 0.01) . Positive correlations between SF IL-1beta concentration and joint effusion (p < 0.01) and between SF TNF-alpha concentration and joint tenderness (p < 0.001) were observed . SF IL-1beta and TNF-alpha were significantly higher in patients with local complications of septic arthritis . In conclusion, high levels of IL-1beta, IL-6 and TNF-alpha were detected in SF of patients with non-GC septic arthritis . Only IL-1beta decreased significantly after day 7 of treatment, but IL-6 and TNF-alpha concentrations were persistently high . SF IL-1beta and TNF-alpha may be useful in predicting the outcome and complications of patients with this disease.

J Chromatogr B Biomed Sci Appl, 1999 Mar 19, 724(2), 281 - 6
Determination of clindamycin in human plasma by high-performance liquid chromatography using coupled columns; Fieger-Buschges H et al.; A rapid automated method has been developed for the determination of clindamycin, a lincosamide antibiotic, in human plasma . Coupled column HPLC was used after precipitation of plasma proteins with a saturated ammonium sulfate solution . As a first step, the drug and internal standard were trapped on a precolumn of LiChrospher 60RP-select B . A reversed-phase Nucleosil 100 C18 HD column then separated drug and internal standard from each other and from remaining plasma components . The assay was validated in the range 0.2-10.0 micrograms ml-1 plasma . The results obtained for accuracy, intra- and inter-day precision complied very well with the generally accepted criteria for bioanalytical assays.

Cell, 1999 Apr 16, 97(2), 175 - 87
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia; Abbott GW et al.; A novel potassium channel gene has been cloned, characterized, and associated with cardiac arrhythmia . The gene encodes MinK-related peptide 1 (MiRP1), a small integral membrane subunit that assembles with HERG, a pore-forming protein, to alter its function . Unlike channels formed only with HERG, mixed complexes resemble native cardiac IKr channels in their gating, unitary conductance, regulation by potassium, and distinctive biphasic inhibition by the class III antiarrhythmic E-4031 . Three missense mutations associated with long QT syndrome and ventricular fibrillation are identified in the gene for MiRP1 . Mutants form channels that open slowly and close rapidly, thereby diminishing potassium currents . One variant, associated with clarithromycin-induced arrhythmia, increases channel blockade by the antibiotic . A mechanism for acquired arrhythmia is revealed: genetically based reduction in potassium currents that remains clinically silent until combined with additional stressors.

Pediatr Clin North Am, 1999 Apr, 46(2), 275 - 87
Pediatric bacterial endocarditis . Treatment and prophylaxis; Brook MM; Endocarditis is a rare but serious complication often related to complex CHD . The incidence, particularly among smaller infants with cyanotic heart disease, seems to be increasing . The pathophysiology is related to a combination of host and bacterial factors that predispose to endothelial colonization and infection . Diagnosis, although occasionally difficult, is life saving, but the treatment is prolonged . Prophylaxis before appropriate procedures may significantly decrease the risk for development in appropriate patients.

Acta Otorrinolaringol Esp, 1999 Mar, 50(2), 142 - 6
{Diagnosis and treatment of cervical esophageal perforation in adults}; Morales-Angulo C et al.; OBJECTIVE: To evaluate the management of cervical esophageal perforation in adult patients . MATERIAL AND METHODS: A retrospective clinical review was made of all cervical esophageal perforations diagnosed in adult patients in the ear, nose and throat department of Marques de Valdecilla Hospital (Santander, Spain) between January 1989 and December 1996 . Age, sex, symptoms, cause of perforation, time to diagnosis, diagnostic studies, treatment, and evolution were obtained from the clinical records . RESULTS: Eleven patients with perforation of the cervical esophagus, age range 38 to 84 years, were seen in the study period . In 8 cases, perforation was caused by a foreign body and 3 cases were iatrogenic (after rigid esophagoscopy) . The most frequent symptoms of presentation were cervical pain and odinophagia . Nine patients were treated with broad-spectrum intravenous antibiotic therapy and no oral feeding . Two patients were treated surgically . There were no complications or need for further surgery in any case . CONCLUSIONS: Small perforations of the cervical esophagus in adult patients produced by foreign body impaction or rigid esophagoscopy can be managed by observation, restricted oral intake, and intravenous antibiotics . Neck exploration should be reserved for patients with signs and symptoms of cervical or mediastinal infection.

Curr Med Res Opin, 1999, 15(1), 47 - 52
Intestinal bacterial overgrowth during chronic pancreatitis; Trespi E et al.; INTRODUCTION: The presence of an intestinal bacterial overgrowth (IBO) in patients with pancreatic insufficiency has been recently suggested to justify the worsening of their clinical conditions despite pancreatic enzyme supplementation . AIM: The purposes of this study were (a) to verify IBO frequency in patients with pancreatic insufficiency owing to chronic pancreatitis and (b) to evaluate the effect of chronic administration of a non-absorbable antibiotic, Rifaximin, in reducing IBO frequency and influencing the clinical picture of the disease . MATERIAL AND METHODS: Thirty-five patients with pancreatic insufficiency owing to chronic pancreatitis and 61 gastro-resected patients without pancreatic disease were studied . The presence of IBO was tested in both groups of patients using the hydrogen breath test with glucose . Chronic pancreatitis patients were subsequently treated with Rifaximin, 400 mg t.i.d for seven consecutive days each month for three months . RESULTS: A positive hydrogen breath test was present in 12 out of 35 (34%) chronic pancreatitis patients and in 13 out 61 (21%) controls (p < 0.002) . In chronic pancreatitis patients an IBO was most likely to be present in the presence of a high ethanol intake, pancreatic microcalcifications, concomitant gallstones, diarrhoea and a history of gastric resection . In all patients with IBO, Rifaximin administration normalised the hydrogen breath test and reduced symptoms . CONCLUSIONS: IBO is frequent in patients with pancreatic insufficiency, particularly in those with a history of gastroduodenal surgery . Treatment with Rifaximin reduces IBO frequency and improves symptoms.

Therapie, 1999 Jan-Feb, 54(1), 183 - 5
{Prospective study on admissions for iatrogenic adverse effects in the emergency service of hospital university center in Poitiers}; Perault MC et al.; Hospital admissions resulting from an adverse drug reaction have been studied in the emergency unit of the university hospital in Poitiers during a 27-day period . This prospective study consisted in documenting all observations considered as an ADR by the medical practitioner in charge of the patient . There were 1235 hospital admissions to the emergency unit during the study period . Thirty-one (2.5 per cent) of admissions were considered to be drug-related . Women were more often affected than men . Patients with ADR were classified taking into account the type of pathology and the drug responsible for the effect . Dermatological and gastrointestinal reactions were predominant . Antibiotic and analgesic drugs were the most common drug groups implicated in causing an ADR.

Przegl Lek, 1998, 55(11), 565 - 71
{Postoperative wound infections . III . Patient related risk factors}; Anielski R et al.; A nosocomial infection is determined by plenty of factors, such as a kind of flora and its virulence, hygiene standard, efficacy of material and instruments sterilisation, technical terms of work organisation in hospital, and other staff and patient related factors . The aim of this study was to establish the risk factors of postoperative wound infection related to patient . The material was 1527 surgically treated patients in the 3rd Surgical Department of the Collegium Medicum of the Jagiellonian University during one year . 66 patients with wounds of the head and 7 patients who died within three days after surgery without any wound infection signs were excluded from the study population . The healing of each wound was observed during the patient's hospitalisation and 30 days after his discharge from hospital, and in orthopedic patients 6 months after discharge . The total number of 132 infected wounds was identified . The population of 1352 wounds healed without any complications was a control group . All the data were recorded in a Wound Infection Register Card and were collected in the computer database . The data were statistically analysed . Relationships between single factor and postoperative wound infection were evaluated using chi-square statistics and in the small group Fisher's exact probability test . Odds ratios and corresponding 95% confidence intervals were computed for all variables . The overall wound infection rate was 8.9% . The significant factors (p < 0.05) were radiotherapy prior to operation, malnutrition, renal failure, respirator treatment, colostomy, tracheostomy in contaminated wounds and neoplastic disease in dirty wounds . Antibiotic therapy and the presence of remote active infection at the time of operation were found also risk factors . CONCLUSION: Statistically significant risk factors of the postoperative wound infection related to patient's condition appeared malnutrition, radiotherapy prior to surgery, renal failure, artificial ventilation, presence of colostomy and coexisting another nosocomial infection at the operation.

Brain Res, 1999 Apr 17, 825(1-2), 46 - 58
Effects of growth factors on the hair cells after ototoxic treatment of the neonatal mammalian cochlea in vitro; Romand R et al.; The aim of this study was to test the possible regenerative potential of several molecules and growth factors such as retinoic acid (RA), insulin, epidermal growth factor (EGF) and transforming growth factors alpha (TGFalpha) and beta (TGFbeta) on the neonatal cochlea in vitro after neomycin intoxication . Our studies show that cochlear sensory epithelium behaves differently while maintained in various culture conditions, although we did not observe regeneration whatever the molecules or growth factors tested . The ototoxic action of neomycin in vitro produced a specific death of hair cells, except in the apical region . Organ of Corti of rats 3 days after birth always presented two regions that responded differently to the antibiotic: a widespread scar region extending from the basal cochlea up to the beginning of the apical turn, where most hair cells had disappeared, and a second region called the resistance region localized in the apex, and which was more or less developed depending on culture conditions . The length of the resistance region was modulated by molecules or growth factors added to the feeding solution suggesting that some of them could produce a protective action on hair cells against neomycin . Slight protection effects may be found with RA and insulin, however, the most definite protection results from the combination of insulin with TGFalpha as shown by the large increase in the length of the resistance region compared to organ of Corti treated with antibiotic alone . The tested molecules and growth factors did not promote cochlear hair cell regeneration in vitro after neomycin treatment, however some of them may offer a protective action against ototoxicity .

Aliment Pharmacol Ther, 1999 Apr, 13(4), 503 - 6
Efficacy of a 1-week regimen of ranitidine bismuth citrate in combination with metronidazole and clarithromycin for Helicobacter pylori eradication; Hoffman JS et al.; BACKGROUND: In order to improve the efficacy and simplicity of the FDA-approved regimen of ranitidine bismuth citrate (RBC) and clarithromycin dual therapy, we added an inexpensive antibiotic (metronidazole), changed the dosage scheme to twice daily dosing, and decreased the duration of therapy to 1 week . METHODS: This was an open label study in which subjects with previously untreated Helicobacter pylori infection documented by serology or endoscopy and confirmed by the 13C-urea breath test received a 1-week course of RBC 400 mg b.d., metronidazole 500 mg b.d . and clarithromycin 500 mg b.d . A repeat breath test was performed 4-6 weeks after completing therapy . RESULTS: Forty-seven out of 50 subjects completed the protocol . Intention-to-treat and per protocol cure rates were 86% and 91%, respectively . The regimen was well tolerated . Study drugs were stopped in two patients due to side-effects . The most common side-effect was self-limited diarrhoea . CONCLUSION: Twice daily RBC-based triple therapy with metronidazole and clarithromycin for 1 week is well tolerated and effective in eradicating H . pylori infection.

Genes Dev, 1999 Apr 15, 13(8), 935 - 45
Control of the nuclear localization of Extradenticle by competing nuclear import and export signals; Abu-Shaar M et al.; The Drosophila PBC protein Extradenticle (Exd) is regulated at the level of its subcellular distribution: It is cytoplasmic in the absence of Homothorax (Hth), a Meis family member, and nuclear in the presence of Hth . Here we present evidence that, in the absence of Hth, Exd is exported from nuclei due to the activity of a nuclear export signal (NES) . The activity of this NES is inhibited by the antibiotic Leptomycin B, suggesting that Exd is exported by a CRM1/exportin1-related export pathway . By analyzing the subcellular localization of Exd deletion mutants in imaginal discs and cultured cells, we identified three elements in Exd, a putative NES, a nuclear localization sequence (NLS), and a region required for Hth-mediated nuclear localization . This latter region coincides with a domain in Exd that binds Hth protein in vitro . When Exd is uncomplexed with Hth, the NES dominates over the NLS . When Exd is expressed together with Hth, or when the NES is deleted, Exd is nuclear . Thus, Hth is required to overcome the influence of the NES, possibly by inducing a conformational change in Exd . Finally, we provide evidence that Hth and Exd normally interact in the cytoplasm, and that Hth also has an NLS . We propose that in Exd there exists a balance between the activities of an NES and an NLS, and that Hth alters this balance in favor of the NLS.

J Neurobiol, 1999 Apr, 39(1), 29 - 40
Concanavalin A protects hair cells against gentamicin ototoxicity in rat cochlear explant cultures; Zheng JL et al.; Degeneration of hair cells and spiral ganglion neurons due to acoustic trauma and various ototoxins is a major cause of hearing loss . Although our previous study demonstrates that specific neurotrophins protect spiral ganglion neurons from ototoxic insult, they do not protect hair cells . In the present experiments, we used postnatal rat cochlear explant cultures to identify molecules that protect hair cells from ototoxic damage . Of 51 compounds examined, only concanavalin A (Con A) significantly protected hair cells from gentamicin . A dose-dependent study of Con A showed that maximal protection occurred at 100 nM . The protective effects of Con A on hair cells were confirmed with confocal microscopy and paraffin sectioning of the cultures . Several experiments were performed to examine the mechanism of protection by Con A . Incubation of Con A with gentamicin did not form a complex and coaddition of Con A and gentamicin to Escherichia coli cultures did not interfere with the antibiotic activity of gentamicin . However, Lyso-Tracker staining and gentamicin immunocytochemistry provided evidence that preincubation with Con A blocked gentamicin uptake into hair cells . Considered together, these findings may help elucidate the ototoxic mechanism of aminoglycoside antibiotics, and suggest that Con A may be of therapeutic value in prevention of aminoglycoside-induced hearing loss.

Spinal Cord, 1999 Mar, 37(3), 201 - 3
Management of false passages in patients practising clean intermittent self catheterisation; Michielsen DP et al.; AIM OF STUDY: Clean intermittent self catheterisation (CISC) is commonly used by patients with impaired bladder emptying . But how to manage acute false passages in patients on CISC? METHODS: Six patients experienced difficulty when performing intermittent catheterisation . Urethrocystoscopy demonstrated a new false passage in all of them . Treatment consisted of urethral stenting with an 14-16F indwelling catheter during 3-6 weeks and antibiotic therapy for 5 days . RESULTS: The false passage disappeared on cystoscopy . During a mean follow up of 10 months (1-28 months), none of these patients developed another false passage . All are practising CISC without any further difficulty . CONCLUSIONS: Analysis of our data suggests that temporary urethral stenting and antibiotic therapy are an excellent management in patients on CISC who develop an acute false passage.

J Biol Chem, 1999 Apr 30, 274(18), 12508 - 16
Molecular characterization of the genes of actinomycin synthetase I and of a 4-methyl-3-hydroxyanthranilic acid carrier protein involved in the assembly of the acylpeptide chain of actinomycin in Streptomyces; Pfennig F et al.; Actinomycin synthetase I (ACMS I) activates 4-methyl-3-hydroxyanthranilic acid, the precursor of the chromophoric moiety of the actinomycin, as adenylate . The gene acmA of ACMS I was identified upstream of the genes acmB and acmC encoding the two peptide synthetases ACMS II and ACMS III, respectively, which assemble the pentapeptide lactone rings of the antibiotic . Sequence analysis and expression of acmA in Streptomyces lividans as enzymatically active hexa-His-fusion confirmed the acmA gene product to be ACMS I . An open reading frame of 234 base pairs (acmD), which encodes a 78-amino acid protein with similarity to various acyl carrier proteins, is located downstream of acmA . The acmD gene was expressed in Escherichia coli as hexa-His-fusion protein (Acm acyl carrier protein (AcmACP)) . ACMS I in the presence of ATP acylated the purified AcmACP with radioactive p-toluic acid, used as substrate in place of 4-MHA . Only 10% of the AcmACP from E . coli was acylated, suggesting insufficient modification with 4'-phosphopantetheine cofactor . Incubation of this AcmACP with a holo-ACP synthase and coenzyme A quantitatively established the holo-form of AcmACP . Enzyme assays in the presence of ACMS II showed that toluyl-AcmACP directly acylated the thioester-bound threonine on ACMS II . Thus, AcmACP is a 4-MHA carrier protein in the peptide chain initiation of actinomycin synthesis.

Cancer Lett, 1999 Feb 8, 136(1), 41 - 6
Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes; DeAtley SM et al.; Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to treat cancer patients . However, the usefulness of this drug is presently limited by the development of a dose-dependent cardiotoxicity . A current hypothesis for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug . We utilized the fluorescent indicator 2',7'-dichlorodihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if reactive oxygen species (ROS) are present, to investigate the ability of ADM to generate reactive oxygen species and the potential protective effect of antioxidants in a cultured cardiomyocyte model . All three of the antioxidants (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicylic acid (5-ASA)) tested in our ADM-treated myocytes provided protection against the oxidative stress induced by the drug . These findings suggest that antioxidants modulate ADM-induced oxidative stress, and they are discussed in terms of a possible therapeutic strategy in the prevention of cardiotoxicity resulting from ADM administration.

Carbohydr Res, 1998 Dec 15, 313(3-4), 265 - 9
Copper(II) binding to tobramycin: potentiometric and spectroscopic studies; Jezowska-Bojczuk M et al.; Protonation and Cu(II) binding by tobramycin, an aminoglycosidic antibiotic, was studied by potentiometry and UV-vis, CD and EPR spectroscopies . A range of mononuclear complexes of a general formula CuHnL was found, with n between 3 and -2 . Tobramycin anchors Cu(II) with an inverted question markNH2, O- inverted question mark chelate of the C-ring of its molecule . The amino and hydroxyl groups of the A-ring of tobramycin also participate in the binding at pH 7 and higher . The resulting structure involves both terminal aminosugar rings but eliminates the donors of the central streptamine unit from the coordination . A comparison between tobramycin and its close analog, kanamycin B {M . Jezowska-Bojczuk, W . Bal and H . Kozlowski, Inorg . Chim . Acta, 275-276 (1998) 541-545} reveals the importance of the A3-OH group for the binding properties of these aminoglycosides.

Int J Dermatol, 1999 Mar, 38(3), 217 - 21
Pemphigus vulgaris: benefits of tetracycline as adjuvant therapy in a series of thirteen patients; Calebotta A et al.; BACKGROUND: Tetracycline is an antibiotic which has been proven beneficial as an immunomodulating drug in the treatment of autoimmune bullous diseases . METHODS: Thirteen hospitalized patients with pempigus vulgaris received tetracycline 2 g/day for 1 month, then 1 g/day for the following 4 weeks . Prednisone 0.5-1 mg/kg/day was then gradually reduced . The control group consisted of seven patients with pemphigus who had received prednisone and azathioprine . RESULTS: A total of 13 patients in the study group achieved cessation of new blister formation within 5.4 days, compared to 23.71 days (p < 0.0001) . The average initial dose of prednisone was 76.53 mg/day for the study group and 118.57 mg/day in the control group (p < 0.014) . The average number of days before reduction of the prednisone dosage could begin was 16.53 days for the study group compared to 31.28 days in the control (p < 0.049) . Total hospitalization time was also significantly lower: 34.07 days (p < 0.001) . The clinical response was not linked to the location of lesions nor to severity of disease . CONCLUSIONS: Tetracycline was shown to be effective as an adjuvant therapy for pemphigus with low toxicity and safety.

Radiology, 1999 Feb, 210(2), 515 - 7
Fatty infiltration of osseous structures: a long-term complication of oleothorax--case report; Freedman BJ et al.; Thoracic imaging of a patient treated for pulmonary tuberculosis with oleothorax therapy before the antibiotic era demonstrated a rare complication . Gross invasion by lipid with subsequent pathologic fracture of the adjacent thoracic vertebra may give rise to symptomatic spinal cord compression . Magnetic resonance imaging is a useful modality for help in diagnosing treatment complications of oleothorax.

Mol Cell Biol, 1999 May, 19(5), 3714 - 26
The chicken beta-globin 5'HS4 boundary element blocks enhancer-mediated suppression of silencing; Walters MC et al.; A constitutive DNase I-hypersensitive site 5' of the chicken beta-globin locus, termed 5'HS4 or cHS4, has been shown to insulate a promoter from the effect of an upstream enhancer and to reduce position effects on mini-white expression in Drosophila cells; on the basis of these findings, it has been designated a chromatin insulator . We have examined the effect of the cHS4 insulator in a system that assays both the level of gene expression and the rate of transcriptional silencing . Because transgenes flanked by insulator elements are shielded from position effects in Drosophila cells, we tested the ability of cHS4 to protect transgenes from position effects in mammalian cells . Flanking of an expression vector with the cHS4 insulator in a colony assay did not increase the number of G418-resistant colonies . Using lox/cre-based recombinase-mediated cassette exchange to control integration position, we studied the effect of cHS4 on the silencing of an integrated beta-geo reporter at three genomic sites in K562 erythroleukemia cells . In this assay, enhancers act to suppress silencing but do not increase expression levels . While cHS4 blocked enhancement at each integration site, the strength of the effect varied from site to site . Furthermore, at some sites, cHS4 inhibited the enhancer effect either when placed between the enhancer and the promoter or when placed upstream of the enhancer . These results suggest that the activity of cHS4 is not dominant in all contexts and is unlikely to prevent silencing at all genomic integration sites.

J Ultrasound Med, 1999 Apr, 18(4), 277 - 81
Diagnosis of necrotizing fasciitis in children; Chao HC et al.; Necrotizing fasciitis is a rare but progressive soft tissue infection . This condition is difficult to recognize in the early phase, when it is often confused with cellulitis . We report the cases of four children with necrotizing fasciitis . The initial presentation in these cases was cellulitis . Fever and soft tissue swelling occurred within 24 h and spreading erythema within 4 to 12 h . Radiologic studies of the lesions showed soft tissue thickening . Ultrasonography of the lesions demonstrated distorted, thickened fascia with fluid accumulation . Well-defined, loculated abscesses were demonstrated in two cases . Although typical dusky skin and purplish patches were not found in our cases, necrotizing fasciitis was strongly suspected on the basis of the clinical course and sonographic findings . Ultrasonography also was used as a guide for aspiration of pus . Gram-stained smears and bacterial cultures yielded the pathogens . The choice of antibiotic therapy was made on the results of smears and culture . All patients survived after immediate surgical debridement, intensive antibiotic therapy, and aggressive wound care . In conclusion, ultrasonography provides a rapid and valuable diagnostic modality for necrotizing fasciitis . The pus obtained through sonographically guided aspiration for bacterial culture can allow identification of the pathogenic organisms.

Oncol Rep, 1999 May-Jun, 6(3), 563 - 8
Aphidicolin glycinate inhibits human neuroblastoma cell growth in vivo; Cinatl J Jr et al.; Aphidicolin is a fungal derived tetracyclic diterpene antibiotic . It is selectively toxic for neuroblastoma (NB) cells in vitro but has no significant effects on the viability of normal human cells and a variety of other tumor entities . We evaluated the antitumoral effects of the water soluble ester aphidicolin glycinate (AphiG) on established human NB xenografts from UKF-NB-3 cells in athymic (nude) mice . Furthermore, we explored the efficacy of direct intraneoplastic and systemic delivery of AphiG . Systemic administration of AphiG (60 mg/kg intraperitoneally, twice per day on 10 consecutive days) significantly suppressed tumor growth but was not able to induce any cures . In contrast, intratumoral AphiG injections (60 or 40 mg/kg/twice a day for 4 days) induced complete tumor regression . Two weeks after the end of treatment no tumor cells were microscopically detectable . Animals were free of tumor for more than 90 days . Histologic examination of inner organs and bone marrow did not reveal any apparent toxic effects of AphiG . These data strongly indicate that AphiG deserves further evaluation as a specific treatment for neuroblastoma.

J Pediatr Gastroenterol Nutr, 1999 Apr, 28(4), 429 - 34
Incidence of dysplasia in pelvic pouches in pediatric patients after ileal pouch-anal anastomosis for ulcerative colitis; Sarigol S et al.; BACKGROUND: The purpose of this study was to evaluate the incidence of dysplasia and the mucosal adaptation patterns of pelvic pouches in children and adolescents who had undergone ileal pouch-anal anastomosis for ulcerative colitis . METHODS: Between 1982 and 1996, 176 pediatric patients with ulcerative colitis underwent ilial pouch-anal anastomosis . Seventy-six patients were followed up after surgery at the Cleveland Clinic . Pouch biopsy specimens were reviewed for dysplasia and to determine mucosal adaptation patterns . Fifty-eight of the 76 patients had an average of three mucosal biopsies during a mean follow-up of 5 years . Demographic and surgical data were abstracted from archives of medical records . All previously obtained pouch biopsy specimens were re-evaluated by a single pathologist to ensure standardized interpretation . RESULTS: No dysplasia was identified in screening specimens of 76 children and adolescents including 5 patients who showed dysplasia in resected colon specimens . The pattern of mucosal adaptation was categorized using previously reported criteria . Type A was defined as normal mucosa or mild villous atrophy with no or mild inflammation . Type B mucosa showed transient atrophy with temporary moderate inflammation followed by normalization of architecture . Type C mucosa was defined as a pattern of persistent atrophy with severe inflammation . In the study cohort, the patterns of mucosal adaptation, type A (56.9%; n = 33), type B (32.8%; n = 19), and type C (10.3%; n = 6), were comparable with those reported in adults . The rate of pouch failure and diagnosis of Crohn's disease were similar in each group and were not related to the specific adaptation pattern . Most of the patients with type C mucosa had clinical symptoms of pouchitis requiring periodic antibiotic therapy . No dysplasia was identified in any biopsy specimen reviewed . CONCLUSIONS: Similar morphologic changes can be seen in ileal pouches in pediatric and adult patients . There seemed to be no increased risk of dysplasia in children and young adults who had undergone ilial pouch-anal anastomosis surgery for ulcerative colitis during a 5 year follow-up . Because the long-term risk of development of dysplasia is unknown, an initial screening should be performed 5 years after the creation of a pelvic pouch in children or when the total disease duration exceeds 7 years . Once identified, patients with Type C mucosa should have annual screening for dysplasia until further data become available.

Vet Clin North Am Small Anim Pract, 1999 Mar, 29(2), 523 - 50, vii
Small intestinal bacterial overgrowth; Johnston KL; It is clear that the exact definition of small intestinal bacterial overgrowth (SIBO) needs to be reappraised in veterinary medicine . Antibiotic responsive enteropathies due to SIBO must be distinguished from those that are not associated with SIBO, such as those caused by a lack of immune tolerance . Once appropriate definitions and criteria for diagnosis are in place, the wide variety of diagnostic procedures that may facilitate the diagnosis can be evaluated with respect to their sensitivity and specificity, and statements about the prevalence and significance of this disorder can be made.

Antibiot Khimioter, 1999, 44(2), 19 - 24
{A new method for the intravital assessment of the functional activity of the membrane transporters performing the efflux of antitumor preparations from the cells of solid tumor specimens}; Bogush TA et al.; A new method for intravital assessment of the functional activity of anticancer drug efflux transporters in intact solid tumor specimens was developed . The method is based on the well-known approach to the transporter functional evaluation by intracellular accumulation of antitumor drugs and particularly the anthracycline antibiotic doxorubicin (Dox) . The main new point of the method providing investigation of intact solid tumor specimens which markedly simplified the procedure is the fact that the intratissue and intracellular accumulation of Dox is determined not by the level of the drug in the tissue but by its fluorescence decrease in the incubation medium . To assess just the intracellular content of Dox and to estimate the transporter functional activity, investigation of the influence of membrane transporter inhibitors such as verapamil (P-gp inhibitor) and sodium azide (inhibitor of all the energy-dependent ABC transporters) on the drug fluorescence decrease in the incubation medium is stipulated . The validity of such an approach was experimentally proved with the specimens of the Ehrlich solid tumor transplants in mice (a sensitive variant of the tumor and the tumor with induced drug resistance) . Biopsy specimens of human breast tumors were investigated with the new method and functional activity of various efflux transporters was revealed: (1) only P-gp, (2) both P-gp and other ABC transporters, (3) only transporters different from P-gp, (4) no functional activity of efflux transporters . The main trends of the further investigation of efflux transporter functional activity in human solid tumors possible for the first time with the use of the new method are defined.

Ophthalmology, 1999 Apr, 106(4), 723 - 8
Tacrolimus (FK506) in the treatment of posterior uveitis refractory to cyclosporine; Sloper CM et al.; OBJECTIVE: To assess the efficacy and side effects of tacrolimus, a potent immunosuppressive macrolide antibiotic, in the treatment of sight-threatening uveitis . DESIGN: A clinical study of tacrolimus in patients who required systemic immunosuppression for control of uveitis, but were refractory to cyclosporine . PARTICIPANTS: Six patients with uveitis were treated: three had Behcet disease, one had microscopic polyangiitis, one had pars planitis, and one had idiopathic retinal vasculitis . INTERVENTION: Patients with sight-threatening uveitis refractory to cyclosporine were treated with tacrolimus . MAIN OUTCOME MEASURES: Intraocular inflammation, visual acuity (VA), neovascularization . Adverse effects of tacrolimus were documented . RESULTS: The posterior uveitis remained controlled in all patients while they were taking tacrolimus . Five of the six patients showed improvement, defined as improvement of two or more lines of Snellen acuity or a decrease in the binocular indirect ophthalmoscopy score (P < 0.05, Sign test) . One patient with Behcet disease showed a marked improvement in best-corrected VA from 1/60 to 6/24 . Two patients with Behcet disease showed a modest improvement in VA in the affected eye and had no disease activity in the other eye . The patient with microscopic polyangiitis was symptomatically improved, and there was no progression of the posterior uveitis . The patient with pars planitis had an improvement in VA from 6/18 to 6/9 . The patient with retinal vasculitis showed partial regression of neovascularization on tacrolimus . Side effects were less troublesome than with cyclosporine . CONCLUSIONS: Tacrolimus (FK506) has a useful role as an immunosuppressive agent for the treatment of sight-threatening uveitis in patients who did not respond to cyclosporine either because of lack of therapeutic effect or unacceptable adverse effects.

Am J Gastroenterol, 1999 Apr, 94(4), 955 - 8
Effectiveness of ranitidine bismuth citrate, clarithromycin, and metronidazole therapy for treating Helicobacter pylori; Smoot DT et al.; OBJECTIVE: There are limited data available from the United States on the effectiveness of ranitidine bismuth citrate (RBC) plus two antibiotics to treat Helicobacter pylori . Therefore, the following study was undertaken to evaluate RBC with two antibiotics, which have been used successfully in combination, to treat H . pylori . METHODS: Adults with and without abdominal symptoms, who had never received H . pylori eradication therapy, were tested for the presence of H . pylori infection either by in-office rapid serology assays or histology . Positive subjects were administered the 13C-urea breath test . Subjects who had a positive urea breath test were then treated with RBC 400 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d . for 10 days . Four to 6 wk after completing antibiotics all subjects were asked to return for a second urea breath test to assess treatment success . RESULTS: Forty-seven of the 50 subjects enrolled into this study completed the antibiotic regimen and returned for a repeat urea breath test . Thirty-seven subjects were negative for H . pylori by urea breath test and 10 were positive, resulting in a 79% eradication rate . Seven subjects (14%) stopped their medication because of side effects . When analysis was performed on the 40 subjects who took > or = 80% of their medication (per-protocol), the eradication rate was 90% . CONCLUSIONS: The combination of RBC with clarithromycin and metronidazole successfully treated H . pylori infection after only 10 days of therapy . The per-protocol eradication rate from this study was similar to that seen with Food and Drug Administration (FDA)-approved regimens . In conclusion, RBC plus clarithromycin and metronidazole should be considered as a first-line treatment regimen for H . pylori infection, and may only need to be taken for a period of 10 days, as opposed to 14 days for FDA-approved regimens.

Neurosurgery, 1999 Apr, 44(4), 807 - 13; discussion 813-4
Brain biopsy using high-field strength interventional magnetic resonance imaging; Hall WA et al.; OBJECTIVE: Lesions within the brain are commonly sampled using stereotactic techniques . The advent of interventional magnetic resonance imaging (MRI) now allows neurosurgeons to interactively investigate specific regions, with exquisite observational detail . We evaluated the safety and efficacy of this new surgical approach . METHODS: Between January 1997 and June 1998, 35 brain biopsies were performed in a high-field strength interventional MRI unit . All biopsies were performed using MRI-compatible instrumentation . Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest . Intraoperative pathological examination of the biopsy specimens was performed to verify the presence of diagnostic tissue, and intra- and postoperative imaging was performed to exclude the presence of intraoperative hemorrhage . Recently, magnetic resonance spectroscopic targeting was used for six patients . RESULTS: Diagnostic tissue was obtained in all 35 brain biopsies and was used in therapeutic decision-making . Histological diagnoses included 28 primary brain tumors (12 glioblastomas multiforme, 9 oligodendrogliomas, 2 anaplastic astrocytomas, 2 astrocytomas, 1 lymphoma, and 1 anaplastic oligodendroglioma), 1 melanoma brain metastasis, 1 cavernous sinus meningioma, 1 cerebral infarction, 1 demyelinating process, and 3 cases of radiation necrosis . In all cases, magnetic resonance spectroscopy was accurate in distinguishing recurrent tumors (five cases) from radiation necrosis (one case) . No patient sustained clinically or radiologically significant hemorrhage, as determined by intraoperative imaging performed immediately after the biopsy . One patient (3%) suffered transient hemiparesis after a pontine biopsy for investigation of a brain stem glioma . Another patient developed scalp cellulitis, with possible intracranial extension, 3 weeks after the biopsy; this condition was effectively treated with antibiotic therapy . Three patients were discharged on the day of the biopsy . CONCLUSION: Interventional 1.5-T MRI is a safe and effective method for evaluating lesions of the brain . Magnetic resonance spectroscopic targeting is likely to augment the diagnostic yield of brain biopsies.

Compr Ther, 1999 Mar, 25(3), 155 - 62
Gonococcal arthritis; Angulo JM et al.; A high index of clinical suspicion; careful culturing of samples from blood, endocervix, urethra, pharynx, skin, synovial fluid and tissue, and rectum; and appropriate antibiotic therapy will rapidly control and prevent more serious complications of disseminated gonococcal infection.

Versicherungsmedizin, 1999 Mar 1, 51(1), 12 - 7
{Atherosclerosis--a chronic infectious disease caused by Chlamydia pneumoniae}; Stille W et al.; Recent investigations allow a controversial but convincing interpretation of the pathogenesis of atherosclerosis (arteriosclerosis) . Atherosclerosis can be apparently the result of ultrachronic persistent infection by Chlamydia pneumoniae and not the result of heterogenous risk factors . The main arguments for the chlamydial genesis are: Correlation of coronary heart disease and other atherosclerotic diseases and antibodies against Chlamydia pneumoniae . Chlamydia pneumoniae could be detected with different techniques (PCR, ICC, immunohistology, electromicroscopy, culture) in a high percentage in atheromas from different sites . Three successful international studies with macrolides in coronary heart disease . Target cells of atherosclerosis (endothelia, macrophages, muscle cells) can be infected by Chlamydia pneumoniae in vitro . Provocation of an arteriitis in animal experiments . The reduction of incidence of atherosclerotic diseases since the 1960s, probably due to advanced antibiotic therapy . Elevated acute-phase proteins and other inflammatory signs (CRP, WBC count, fibrinogen) briefly before occurrence of myocardial infarction . There are good arguments for intervention studies in coronary heart disease and other manifestations of atherosclerosis . The relevant antibiotics are licensed for chlamydial infections, cheap and safe . Meticulous records and long-term observation of patients need to be developed, sometimes contrary to interests of the pharmaceutical industry.

Patol Fiziol Eksp Ter, 1999 Jan-Mar, (1), 6 - 11
{Bacterial infection in the etiology of bronchial asthma}; Oehling A; The role of bacterial infection in etiopathogenesis of bronchial asthma should not be underestimated . The use of maintenance instead of causal treatment is not valid . We insist on antibiotic therapy and long-term bacterial immunotherapy of bronchial asthma and support value of bacterial antigen potentiating the action of inhalation antigen . This is confirmed by our treatment results which are very good.

J Bacteriol, 1999 Apr, 181(8), 2507 - 12
Mitomycin resistance in Streptomyces lavendulae includes a novel drug-binding-protein-dependent export system; Sheldon PJ et al.; Sequence analysis of Streptomyces lavendulae NRRL 2564 chromosomal DNA adjacent to the mitomycin resistance locus mrd (encoding a previously described mitomycin-binding protein {P . Sheldon, D . A . Johnson, P . R . August, H.-W . Liu, and D . H . Sherman, J . Bacteriol . 179:1796-1804, 1997}) revealed a putative mitomycin C (MC) transport gene (mct) encoding a hydrophobic polypeptide that has significant amino acid sequence similarity with several actinomycete antibiotic export proteins . Disruption of mct by insertional inactivation resulted in an S . lavendulae mutant strain that was considerably more sensitive to MC . Expression of mct in Escherichia coli conferred a fivefold increase in cellular resistance to MC, led to the synthesis of a membrane-associated protein, and correlated with reduced intracellular accumulation of the drug . Coexpression of mct and mrd in E . coli resulted in a 150-fold increase in resistance, as well as reduced intracellular accumulation of MC . Taken together, these data provide evidence that MRD and Mct function as components of a novel drug export system specific to the mitomycins.

Semin Respir Infect, 1999 Mar, 14(1), 48 - 58
Indications for draining a parapneumonic effusion: an evidence-based approach; Heffner JE; A patient with pneumonia who develops a parapneumonic effusion challenges the physician to determine the need for pleural fluid drainage . This determination is influenced by multiple factors including the patient's general state of health, the existence of comorbidities, the virulence of the underlying pathogen, and the extent of the pneumonia that dictate clinical outcome and the relative risks and benefits of drainage . The presence of intrapleural pus represents the only factor that clearly establishes the need for drainage, although most experts recommend draining pleural fluid that is positive by Gram's stain or culture for a pathogen . Other factors such as the extent of the patient's pneumonia, severity of systemic signs of inflammation, radiographic features of the effusion, and pleural fluid chemical profile assist clinical decision making . The fundamental principle that guides therapy is the need to promptly and effectively drain pleural fluid whenever it appears likely that it will progress to a frank empyema with antibiotic therapy alone.

Semin Respir Infect, 1999 Mar, 14(1), 9 - 17
Pathophysiology of pleural space infections; Antony VB et al.; The pleura responds to the presence of infecting organisms with a vigorous inflammatory response associated with an exudation of white blood cells and proteins . Changes in pleural permeability lead to formation of an exudative pleural effusion . The pleural mesothelial cell is the primary cell lining the pleural space and, when activated by the presence of organisms, initiates the inflammatory response by releasing a battery of chemokines and cytokines . Mesothelial cells are actively phagocytic and also release oxidants and proteases . The acute inflammatory process may resolve with appropriate antibiotic therapy and drainage leaving minimal fibrosis . However, under certain circumstances vigorous pleural fibrosis with scarring and loss of delineation of pleural surfaces can occur . Recognition of the stage of development of the empyema is an important clinical judgement that can affect outcome . The pathogenesis of infections of the pleural space and the role played by the various cell types is delineated in this article.

Semin Respir Infect, 1999 Mar, 14(1), 3 - 8
The definitions and epidemiology of pleural space infection; Strange C et al.; Infections of the pleural space are caused by a diverse group of clinical conditions that include trauma, post-operative states, and pneumonia . Although pleural effusions accompany bacterial pneumonia in up to 60% of patients, they uncommonly influence management because the effusion in most patients disappears with antibiotic administration . Unfortunately, the large number of patients with pneumonia provide an abundant supply of patients who fail to respond to antibiotic administration alone and subsequently present with pleural fluid loculation, pleural sepsis, or empyema . This article provides an overview of the classification schemes that have been used to characterize pleural space infections and highlight the epidemiology of those patients who present with complicated parapneumonic effusions and empyema.

Aust Vet J, 1999 Mar, 77(3), 161 - 3
Surgical treatment of gastric leiomyoma in a dog; Beck JA et al.; A 12-year-old entire male Maltese terrier was presented with a 1 month history of vomiting and haematemesis . Microcytic hypochromic anaemia was detected . Abdominal radiography, ultrasonography and gastric endoscopy identified a discrete intramural mass in the pyloric antrum . An ulcerated leiomyoma was removed by a partial-thickness intraluminal resection of the gastric wall . The dog recovered well and is free from clinical signs 20 months after surgery.

Curr Pharm Des, 1998 Jun, 4(3), 181 - 201
Cytotoxics derived from distamycin A and congeners; Cozzi P et al.; Distamycin A is an antibiotic, characterised by an oligopeptidic pyrrolocarbamoyl frame ending with an amidino moiety, which binds reversibly to DNA minor groove with high selectivity for TA-rich sequences and shows antiviral and antiprotozoal activity . Distamycin was used as DNA sequence selective vector of alkylating functions, leading to a substantial increase of cytotoxicity in comparison to that, very weak, of distamycin itself . The benzoyl nitrogen mustard derivative of desformyldistamycin, tallimustine, was selected as a candidate antineoplastic drug in view of its strong activity against a series of experimental tumors . Tallimustine, like distamycin, shows DNA selective binding to TA-rich sequences but its cytotoxicity is not associated with DNA strand breaks and interstrand crosslinking, at variance with classical phenyl nitrogen mustards . Tallimustine represents an important model for the design of new minor groove alkylating agents derived from distamycin and analogues, including the so-called lexitropsins, sequence-reading oligopeptides in which one or more N-methyl-pyrrole units of distamycin are replaced by imidazole or other rings . The structural features of the alkylating moieties and binding frames, the antitumor activities and the mechanism of action of most representative cytotoxics derived from distamycin and congeners are discussed . Some of these, recently reported, show an activity profile apparently superior to tallimustine . Finally, a concise survey of representative hybrid compounds in which known non-alkylating cytotoxic agents or their active moieties have been tethered to distamycin and congeners is presented and briefly discussed . These compounds witness the attention paid to this approach on the basis of the interest for the DNA binding features of distamycin A.

J Emerg Med, 1999 Mar-Apr, 17(2), 255 - 9
A new hazard for windsurfers: needlefish impalement; Link KW et al.; Marine-related injuries and envenomations are common to the coastal physician . Needlefish injuries, which occur almost exclusively in the Indo-Pacific region, have not previously been reported along the Atlantic seaboard . This case report describes a penetrating injury to the lower extremity from a needlefish . Treatment is guided by general resuscitative procedures as well as antibiotic therapy directed against infections unique to the marine environment.

Am J Orthop, 1999 Mar, 28(3), 168 - 78
Septic arthritis; Perry CR; Hematogenous septic arthritis causes pain and effusion and begins with inoculation of the joint with bacteria from the intravascular space . The degradation of ground substance by enzymes released and activated by the acute inflammatory response, toxins and enzymes produced by the bacteria, and T lymphocytes stimulated during the delayed immune response, leads to destruction of the articular cartilage . Whether a given patient will develop a septic joint or a less severe form of infection is dependent upon characteristics of the bacterial strain and of the individual's host defenses . Management consists of systemic antibiotic therapy and decompression of the joint . Synovectomy, salicylate administration, and continuous passive motion are adjuvant therapies that have not as yet not been proved to be of benefit.

J Emerg Med, 1999 Mar-Apr, 17(2), 311 - 22
Cerebral ventricular shunts; Naradzay JF et al.; Cerebral ventricular shunts are siphoning devices used to treat hydrocephalus . They are placed within cerebral ventricles and peripheral cavities such as the ventricular atrium or peritoneal cavity . Complications include obstruction of cerebral spinal fluid (malfunction) and infection . Morbidity and mortality rates are high when shunt malfunction and infection are not treated emergently . This report summarizes the physical examination of patients with ventricular shunts, reviews the type of shunts commonly used, discusses shunt malfunctions (causing overshunting or undershunting of cerebrospinal fluid) and infections, and makes recommendations concerning empiric antibiotic therapy for shunt infection . The technique of tapping a shunt is presented for management of patients with elevated intracranial pressure that does not respond to non-invasive maneuvers to lower the pressure.

Sex Transm Infect, 1998 Oct, 74(5), 361 - 3
How well is pelvic inflammatory disease managed in general practice? A postal questionnaire survey; Huengsberg M et al.; OBJECTIVE: Many patients with pelvic inflammatory disease (PID) present to their general practitioners . Chlamydia trachomatis is the organism most commonly implicated in this condition . This study aims to examine how well PID is managed in the primary care setting and highlight areas for improvement . METHODS: The study was performed by sending postal questionnaires to 180 randomly selected general practitioners in Birmingham . Given the example of a woman presenting clinically with PID, the doctors were asked questions on diagnosis and treatment . To assess factors that may influence the answers, they were also asked about their sex, year of qualification, and postgraduate training . RESULTS: 139 questionnaires (77%) were returned . 91.4% of the respondents feel confident in managing patients with PID, and only 9.3% would usually refer these patients on . However, 54.7% do not perform an endocervical swab for C trachomatis, 37.4% do not include anti-chlamydial antibiotics in their treatment regimen, and 24.5% do not advise sexual partners to be screened . Female doctors, those with higher degrees, or obstetrics and gynaecology experience were more likely to give anti-chlamydial therapy, but no factors of the respondents significantly influenced contact tracing behaviour . CONCLUSIONS: The management of a patient presenting with PID should include investigation for C trachomatis and treatment with an appropriate antibiotic . As PID is often a sexually transmitted disease, contact tracing of sexual partners should be undertaken . The study suggests that a significant proportion of general practitioners would not have offered optimal management to patients with PID.

Biochemistry, 1999 Apr 6, 38(14), 4342 - 54
Mechanistic studies on the base-catalyzed transformation of neocarzinostatin chromophore: roles of bulged DNA; Xi Z et al.; Nucleic acid bulges have been implicated in a number of biological processes and are specific cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore (NCS-chrom) in a base-catalyzed, radical-mediated reaction . Studies designed to elucidate the detailed mechanism of the base-catalyzed activation of NCS-chrom and to evaluate the roles of bulged DNA in its activation are described . They show that nucleobases in the DNA bulge are not required to form an effective bulge pocket but enhance the binding of the wedge-shaped activated drug molecule . Analysis of solvent deuterium isotope effects on NCS-chrom degradation and DNA cleavage efficiency experiments suggests that the spirolactone biradical 6 is a relatively stable species and that intramolecular quenching of the C2 radical of 6 to form the biologically active cyclospirolactone radical 7a occurs first (pathway a in Scheme 2), leaving the C6 radical to abstract the hydrogen atom from the DNA deoxyribose and to form the cyclospirolactone 8 . Binding of the activated drug at the bulge site is required, but not sufficient, for efficient 8 formation, whereas cleavage of bulged DNA is not essential . Efficient generation of 8, but inefficient DNA damage generation, comes mainly from the likely high off-rate of 7a binding . The finding that thymidine 5'-carboxylic acid-ended oligonucleotide fragment can be formed in the reaction suggests that the process of DNA cleavage is rather slow and that sequential oxidations of the target 5'-carbon are possible . Study of the effect of solvent (methanol) concentration on NCS-chrom degradation indicates that bulged DNA acts to assist the intramolecular quenching of the radical at C2 by C8' ' of the naphthoate moiety by excluding solvent from the binding pocket, thus preventing the formation of spirolactones 9, and by blocking radical polymerization . Because in the absence or near absence of solvent methanol 8 formation does not reach even 10% that formed in the presence of bulged DNA, it is possible that the DNA bulge also induces a conformational change in the drug to promote the intramolecular reaction.

Clin Infect Dis, 1999 Mar, 28(3), 569 - 74
Successful oral doxycycline treatment of Lyme disease-associated facial palsy and meningitis; Dotevall L et al.; Twenty-nine patients, aged 11-79 years (mean, 50 years), with Lyme neuroborreliosis, facial nerve palsy, and meningitis were treated with oral doxycycline (daily dose, 200-400 mg) for 9-17 days in a prospective, nonrandomized study . Facial paresis was bilateral in eight (28%) of the 29 patients . Twenty-six patients (90%) recovered without sequelae within 6 months, while three of the patients with bilateral facial palsy at admission had remaining paresis at follow-up . In five patients, contralateral facial paresis developed 1-12 days after initiation of therapy, and two patients were retreated with antibiotics . Posttreatment examinations of cerebrospinal fluid showed a marked decrease of inflammatory cells and protein concentrations compared with pretreatment levels in all followed up patients . The favorable clinical outcome agrees with findings of other reports on intravenous antibiotic therapy for Lyme disease-associated meningitis with facial palsy . Our conclusion is that oral doxycycline is an effective and convenient therapy for Lyme disease-associated facial palsy.

Intensive Care Med, 1999 Feb, 25(2), 146 - 56
The management of severe acute necrotising pancreatitis: an evidence-based review of the literature; Wyncoll DL; Clearly the main determinant of outcome in severe acute pancreatitis is the extent of pancreatic necrosis and the subsequent risk for the development of infected necrosis . A thorough assessment using appropriate scoring systems and the early use of dynamic contrast-enhanced CT will highlight those patients likely to benefit from higher dependency or intensive care . Despite numerous suggested specific therapies there is still no Grade A evidence that any confers a significant mortality benefit . However, general supportive measures should include vigorous replacement of fluid losses to correct the circulating volume, correction of electrolyte and glucose abnormalities, and respiratory, cardiovascular and renal support as necessary . Those patients with infected pancreatic necrosis or deteriorating organ systems should undergo surgery . Patients with sterile necrosis should receive a broad-spectrum prophylactic antibiotic which adequately penetrates pancreatic tissue . Due attention should also be paid to nutritional support, for which a jejunal feeding tube with EN is recommended as early as is achievable.

Eur J Clin Microbiol Infect Dis, 1999 Jan, 18(1), 62 - 5
Diagnosis and follow-up of Whipple's disease by amplification of the 16S rRNA gene of Tropheryma whippelii; Pron B et al.; Amplification of the 16S rRNA gene of Tropheryma whippelii was performed in eight patients with Whipple's disease and 34 control patients to confirm a diagnosis of Whipple's disease and to monitor the course of disease . Polymerase chain reaction (PCR) tests were positive before treatment in 13 of 15 tissue samples from Whipple's disease patients (gut 8/8; lymph nodes 2/2; bone marrow 1/2; peripheral blood 2/3), in contrast to none of 54 tissue samples from controls . PCR tests converted to negative within 4-6 months in six of the Whipple's disease patients undergoing therapy . These results show that PCR is a reliable and useful tool for diagnosis of Whipple's disease and for monitoring bacterial elimination during antibiotic therapy.

J Neurosurg Sci, 1998 Sep, 42(3), 165 - 71; discussion 171-2
Actinomycosis of the central nervous system: surgical treatment of three cases; Puzzilli F et al.; Three cases of actinomycotic brain infection are described, 2 of which manifested as cerebral abscess, the third as epidural empyema . Complete resolution of the infection was always achieved by means of surgical treatment and prolonged antibiotic therapy . The cases reported emphasize the importance of a combined approach in the treatment of this unusual cause of brain infection.

Int J Pediatr Otorhinolaryngol, 1998 Nov 15, 46(1-2), 9 - 13
Outpatient management of acute mastoiditis with periosteitis in children; Niv A et al.; Children with acute mastoiditis with periosteitis are conventionally hospitalized for parenteral antibiotics and/or surgical treatment . However, if possible, effective and safe outpatient treatment is desirable . During a 36-month period, outpatient parenteral antibiotic therapy (once daily i.m . ceftriaxone) was evaluated in 32 children with acute mastoiditis, with clinical evidence of periosteitis . Inclusion criteria included otomicroscopic evidence of acute otitis media (AOM), displacement of the pinna, retroauricular swelling, erythema and tenderness . The treatment consisted of wide myringotomy and administration of i.m . antibiotics . Daily visits, by a combined team of an otolaryngologist and pediatric infectious disease specialist, were considered essential . Fourteen children (43%) were treated initially in the hospital (and subsequently as outpatients) and 18 (57%) children were treated entirely as outpatients . Mean duration of outpatient treatment was 7 days (range: 4-10) . The overall clinical cure rate was 96.8% . One child underwent simple mastoidectomy . No serious side effects were observed . Our data suggests that many children with acute mastoiditis with periosteitis can be managed successfully and safely as outpatients by a combined team of otolaryngologists and infectious disease specialists.

Am Surg, 1999 Apr, 65(4), 338 - 40
Limited utility of preoperative studies in preparation for colostomy closure; Pokorny RM et al.; Numerous diagnostic and therapeutic practices are used in an attempt to reduce the morbidity of colostomy closures . Our principal aim was to evaluate the role of preoperative studies, specifically barium enemas and endoscopic examinations, performed before colostomy closures . Additionally, we wished to identify other practices involved in the perioperative management of patients undergoing colostomy closure that influenced morbidity . The records of 100 consecutive patients who underwent elective colostomy closure at University of Louisville Hospital between January 1989 and July 1995 were reviewed . Wound infection was the most common complication (12%) . Various bowel preparations were equivalent in efficacy and did not influence the complication rate . Intermittent wound irrigation with antibiotics for 3 days postoperatively, via subcutaneous drains, was associated with a low incidence of incision infection . Preoperative barium enema or sigmoidoscopy were often performed but rarely useful . Performing these examinations merely increased hospital cost without a corresponding decline in morbidity.

Vopr Virusol, 1999 Jan-Feb, 44(1), 35 - 9
{Effect of gentamycin on persistence of tick-borne encephalitis}; Pogodina VV et al.; Effect of gentamicin, an aminoglycoside antibiotic, on the persistence of tick-borne encephalitis (TBE) virus in Syrian hamsters and Macaca iris in remote periods (70-434 days) after inoculation is studied . Attempts at virus isolation from animals treated with gentamicin failed . Unlike other aminoglycosides, e.g . streptomycin, gentamicin exerted no immunodepressive effect; moreover, immunocorrection was observed in some experiments on monkeys and hamsters . None of the 10 previously tested antibiotics elicited such an effect or inhibited the persisting TBE virus . Morphological study of the central nervous system in hamsters and monkeys showed that injection of gentamicin did not cause an exacerbation of chronic encephalitis . The mechanism of immunocorrecting effect of gentamicin is to be further investigated.

Ophthal Plast Reconstr Surg, 1999 Mar, 15(2), 77 - 8
Exposure of expanded polytetrafluoroethylene-wrapped hydroxyapatite orbital implant: a report of two patients; Choo PH et al.; PURPOSE: Hydroxyapatite (HA) spheres used to replace volume after an enucleation are often wrapped with autologous tissue before orbital implantation . Man-made materials are less expensive and pose no risk for viral transmission . The use of expanded polytetrafluoroethylene (ePTFE) to wrap HA spheres was evaluated . METHODS: The medical records of 2 consecutive patients who underwent uncomplicated implantation of an HA sphere wrapped in ePTFE were reviewed . RESULTS: An unusual reaction to the ePTFE material that was nonresponsive to topical or systemic antibiotic therapy developed in these 2 patients . Eventual wound erosion and bacterial infection of the implant necessitated its removal . CONCLUSIONS: Although well tolerated in other surgeries, ePTFE, when used to wrap HA spheres and placed into the orbit, may cause persistent conjunctival discharge, pyogenic granuloma formation, and eventual wound erosion . Therefore, the use of this material to wrap HA spheres is not recommended.

Haematologica, 1999 Mar, 84(3), 222 - 5
Early detection by ultrasound scan of severe post-chemotherapy gut complications in patients with acute leukemia; Picardi M et al.; BACKGROUND AND OBJECTIVE: Acute leukemia patients may develop life-threatening gut complications after intensive chemotherapy . We evaluated the role of abdominal and pelvic ultrasound (US) examination in early detection of these complications . DESIGN AND METHODS: A cohort of twenty adult acute leukemia patients undergoing intensive chemotherapy for remission induction entered the study . All chemotherapy regimens included cytarabine by continuous i.v . infusion for several days . RESULTS: Three patients had severe gut complications: 2 cases of enterocolitis and 1 case of gall bladder overdistension in the absence of calculi . In all cases the abnormality was documented by US examination: US scan showed thickening of the intestinal wall (two cases), and gall bladder overdistension with biliary sludge (one case) . Immediate medical care included bowel rest, a broad-spectrum antibiotic, antimycotic treatment, and granulocyte colony-stimulating factor . All patients recovered from the complication . INTERPRETATION AND CONCLUSIONS: We believe that the favorable outcome obtained in our small series can be attributed to early diagnosis followed by appropriate treatment . Early recognition by US and immediate medical management can lead to complete recovery of severe intestinal complications in patients with acute leukemia undergoing intensive chemotherapy.

Gen Pharmacol, 1999 Feb, 32(2), 215 - 8
Intermediate dose of methotrexate toxicity in non-Hodgkin lymphoma; Uluoglu C et al.; Methotrexate (MTX) is the chemotherapeutic for which the serum levels can be detected . If the MTX level is detected in time, high toxicity risk can be decreased . In this study, intermediate doses of MTX (1 g/m2) infusions are administered to B-cell non-Hodgkin lymphoma patients between 3 and 13 years old . The toxicity of MTX in accordance with serum levels and the toxicity of other combined drugs are investigated . Blood samples were collected consecutively, and MTX levels were detected by high-performance liquid chromatography . When hematological, gastrointestinal, and renal toxicity scores were compared with the 24-h serum levels of MTX, they showed a significant positive correlation . Hematological toxicity scores increased by Ifosfamide, Etoposide, and Cytarabine combined with MTX without altering the serum levels . Antibiotic combination with MTX has no effect on the toxicity scores . In conclusion, if MTX is combined with other myelosuppressive, hepatotoxic, and nephrotoxic drugs, the measurement of MTX serum levels alone is not a sufficient parameter to show the toxicity.

Semin Ophthalmol, 1994 Sep, 9(3), 193 - 9
Intraorbital foreign bodies; Michon J et al.; A high index of suspicion is important in evaluating any penetrating orbital injury . Likewise, any chronically infected orbit must be suspected of harboring an IOrbFB . Careful history and examination are mandatory for both clinical and medicolegal purposes . Appropriate imaging studies, usually including CT scanning, must be employed . Antibiotic therapy may be crucial in preventing infectious complications, including those involving the central nervous system . The decision regarding surgery must be individualized and should consider visual status, form and composition, and localization of an IOrbFB . The possibility of orbitocranial extension should always be considered and ruled out . Following these general rules, an injury with a small but real potential for clinical disaster may be mitigated, and visual and neurological outcome may be optimized.

Can J Hosp Pharm, 1994 Apr, 47(2), 53 - 8
Impact of a target drug monitoring program on the usage of clindamycin; Gin AS et al.; The use of parenteral clindamycin at the Health Sciences Centre had not been amendable to traditional cost containment strategies . Clindamycin was targeted through a Target Drug Monitoring (TDM) Program to improve its appropriate use . A retrospective audit was conducted to serve as a baseline . In the concurrent phase, the TDM pharmacist reviewed and assessed clindamycin cases based on approved criteria . Those cases which failed to meet the criteria were targeted in order to convert clindamycin to alternative agents . The concurrent TDM program reviewed 339 cases of clindamycin over a 32-week period, of which 76 cases (22.4%) failed to meet the criteria and were targeted . Of the 76 recommendations, 48 (63.2%) were accepted . Cost-avoidance due to direct intervention was approximately $16,000 annualized compared to $28,000 estimated from the retrospective audit . Fiscal year-end antibiotic usage indicated a dramatic decline (32%) in clindamycin use . Net savings of $37,600 were attributed to modification of physician prescribing . The TDM program was successful in identifying areas of inappropriate clindamycin use and correcting them by direct interaction with the prescriber(s).

Hosp Pharm, 1994 Mar, 29(3), 205 - 6, 208-11
Use of severity-indexed medication error reports to improve quality; Schneider PJ et al.; A severity-indexed medication error reporting system using data from voluntary incident reports has provided enough information to target opportunities for quality improvement . Reports are ranked by severity and categorized by error type, system breakdown, drug category, and nursing unit . Specific reports are generated for review by different quality improvement committees in the hospital . Based on these data and the actions of these quality improvement committees, four problem areas in medication use have been identified . Recommendations for improvements have been made to solve problems with late IV antibiotic doses, narcotic errors, anticoagulant errors and transcription errors . Two of these initiatives have resulted in objective improvement . Two others are being actively pursued to resolve medication related problems.

Hosp Pharm, 1993 Oct, 28(10), 986 - 8
Imipenem-induced seizure: a case of inappropriate, excessive, and prolonged surgical prophylaxis; Hunter WJ; Imipenem-cilastatin is a broad spectrum antibiotic that is generally used for antibiotic-resistant hospital-acquired infections . Imipenem has been reported to cause CNS toxicity including seizures in 1.5-10% of patients . The authors present a case in which imipenem, inappropriately utilized for surgical prophylaxis in excessive doses (1 gram every six hours) and for a prolonged period of time (24 days), induced a tonic-clonic generalized seizure in a patient with no history of seizure activity . The identification of this ADR lead to a number of clinical and administrative actions within our institution . Drug-induced seizures have occurred and will continue to occur as healthcare professionals exceed recommended dosing guidelines to treat critically ill patients . As pharmacists, it is extremely important to use therapeutic drug monitoring and pharmaceutical care principles to assist physicians in individualizing drug regimens for our patients to prevent these ADRs from occurring, thereby significantly effecting patients' outcomes.

Hosp Formul, 1993 Jan, 28 Suppl 1, 51 - 4
Impact of nosocomial infections on hospital costs; Nightingale CH; Modifications in antibiotic programs for treatment of nosocomial infections can result in significant cost savings within a hospital . Most hospitals initially treat nosocomial infections empirically, based on their epidemiologic history . Designed to be effective against a broad range of possible pathogens, this type of therapy usually includes two or more drugs administered parenterally . This is expensive because the total cost of treatment includes the cost of not only multiple drug therapy but also the materials and labor needed to prepare and administer them . "Streamlining of therapy" to a single oral or parenteral agent can usually be done once more definitive information is known about the pathogen and the patient's condition . This approach maximizes therapeutic effectiveness and reduces costs . Streamlining therapy for nosocomial infections has helped Hartford Hospital decrease the antibiotic budget from 30 to 15% of the total drug budget, resulting in annual cost savings of $150,000 to $250,000.

Can J Hosp Pharm, 1992 Oct, 45(5), 193 - 7
Characterization of errors detected during central order review; Ho L et al.; Characterization of prescribing errors detected by dispensary pharmacists in a tertiary-care teaching hospital is described . During the 25 week study period, 1330 prescribing errors were identified from a total of 237,798 medication orders processed by the pharmacy, representing a rate of 5.6 errors per 1000 orders . Resident physicians wrote more errant medication orders than any other physician class . Errors most often occurred on the general medicine teaching wards . The most common drug classes implicated were non-formulary medications and antibiotics . Approximately 11% of errors were defined as potentially fatal or severe (Type A) errors, 7% were potentially serious (Type B), 21% were potentially significant (Type C) and 61% were problem orders (Type D) based on a classification system of severity . The most common error types were inappropriate dosing of antibiotics and the prescribing of medications for patients who had a potential conflicting allergy history . The acceptance of pharmacists' suggestions was 67% . The study identified three major areas where future educational and corrective measures could be aimed: adherence to the formulary, antibiotic prescribing and allergy validation.

World Hosp, 1992, 28(2), 25 - 7
Concerted action programme on quality assurance in hospitals in Norway; Piene H et al.; Below are the results of the assessment phase of a research project conducted in Norway . This project dealt with various quality assurance strategies and their effect on improvement of care with respect to: prophylactic antibiotic use in surgery; preoperative assessment; keeping records and prevention and therapy of bedsores.

Can J Hosp Pharm, 1991 Oct, 44(5), 239 - 43
Quality assurance of data collection in an aminoglycoside dosing service; Lew KH et al.; An aminoglycoside dosing service (ADS) has been in existence at the Hospital since 1984 . As part of an overall Quality Assurance (QA) plan for the service, an audit was conducted to ensure that all necessary data were available to allow for proper interpretation of the serum aminoglycoside levels . The initial audit revealed complete documentation of required data in 75% of PRE-dose levels and 63% of POST-dose levels drawn . Several problems were identified: staff were not aware of procedures on how to complete the serum antibiotic level requisition forms; inaccurate assumptions of infusion times were made by pharmacists; and discrepancies were found to exist in the Hospital's Laboratory Manual and Pharmacy Intravenous Medication Manual . Corrective action was initiated through: education on proper documentation on the serum antibiotic level requisition forms through the hospital-wide distributed Pharmacy Bulletin; revision of the Hospital's Laboratory Manual and Pharmacy Intravenous Medication Manual; communication with head nurses to emphasize the need for documentation of infusion times; and active follow-up with nurses on missing information by the clinical pharmacist . A re-audit was initiated following implementation of the corrective actions . Complete documentation of required data increased to 93% with PRE-dose levels and 84% with POST-dose levels . This improvement was statistically significant (p less than 0.001).

Hosp Formul . 1990 Jul;25(7):752, 756.
Improving drug usage evaluation with microcomputer database software; Loertscher MV et al.; The use of microcomputer database software can help overcome many of the potential weaknesses of criteria-based drug usage evaluation (DUE) through the collection and assessment of drug use statistics on a broad basis . By allowing for more systematic and comprehensive data analyses, database software can target the selection of the most appropriate DUE topics; improve the accuracy, efficiency, and acceptance of DUE reports; and enhance the overall therapeutic- and cost-effectiveness of drug use in the institutional setting . The development of antibiotic use statistics in the area of surgical prophylaxis is presented as an example, with recommendations for similar applications in other therapeutic areas.

Hosp Pharm . 1991 Aug;26(8):693, 696.
The nontraditional use of commercial advertising in prescriber education; Hemming MP; The availability of prescribing guidelines for antibiotics stimulated audits of antibiotic use in Melbourne hospitals . Following such audits, an advertising campaign to change prescribing was conducted at The Royal Melbourne Hospital . The success of this pilot study prompted a wider campaign to examine the power of marketing techniques in influencing prescribing . The Therapeutics Committee of the Victorian Medical Postgraduate Foundation (VMPF-TC) was established to administer this project and to undertake promotional activities . The Victorian Drug Usage Advisory Committee, which was established to advise the Minister for Health on matters relating to drug usage in public hospitals, recommended that posters be used in hospitals to promote rational and cost-effective drug therapy . The VMPF-TC was asked to prepare posters for sale to hospitals on the basis that economies of scale could make it financially viable . Oral rather than parenteral administration of antibiotics was chosen as the theme for the first poster.

Hosp Formul, 1991 Feb, 26(2), 120 - 30
Achieving an effective committee through reorganization: the Ohio State University Hospital's experience; Lewis RP et al.; The P & T Committee at Ohio State University (OSU) Hospitals, Columbus, is unique in that it accomplishes the bulk of its tasks through subcommittees . Four subcommittees are currently in place: a formulary subcommittee, a policy and surveillance subcommittee, an antibiotic subcommittee, and a therapeutic drug monitoring subcommittee . An advantage to this method of organization is that it allows for much more medical staff involvement in P & T Committee activities . Other unique aspects of this P & T Committee are that it is responsible for maintaining both an inpatient and outpatient formulary, and it provides decision-making services for a specialty cancer hospital . Expansion of their drug usage evaluation program, further development of their therapeutic monitoring program, and improved communication with the medical staff are future goals of this P & T Committee.

Hosp Formul, 1990 Apr, 25(4), 446 - 8, 450
Multidisciplinary approach to cost reduction of C-section prophylaxis; Todd MW et al.; Runaway cefoxitin costs prompted a thorough usage evaluation by the P & T Committee, the antibiotic review subcommittee, and the pharmacy department at this 450-bed teaching hospital . C-section prophylaxis accounted for 25% of all cefoxitin usage . With the assistance of the ob/gyn department, a major campaign was initiated to alter prescribing habits and evaluate more cost effective prophylaxis . Single dose cefotetan replaced multidose cefoxitin regimen for a 6-month trial basis . Annualized cost savings for drug and supplies were approximately $49,086, and no change in morbidity was noted . The ob/gyn department then agreed, at the request of the antibiotic subcommittee, to conduct a trial comparing single dose cefotetan with single dose cefazolin in women undergoing C-section . The results indicated that both treatments were equally effective, consequently, cefazolin replaced cefotetan, producing an additional $10,384 annual savings . Overall, our approach to C-section cost reduction resulted in a total of $59,470 annual savings and demonstrated the effectiveness of an organized multidisciplinary approach.

Eur J Biochem, 1999 Apr, 261(1), 98 - 107
Biosynthesis of ansatrienin (mycotrienin) and naphthomycin . Identification and analysis of two separate biosynthetic gene clusters in Streptomyces collinus Tü 1892; Chen S et al.; The polyketide chains of the two ansamycin antibiotics, ansatrienin (mycotrienin) and naphthomycin produced by Streptomyces collinus are assembled using 3-amino-5-hydroxybenzoic acid (AHBA) as a starter unit . The gene encoding AHBA synthase, an enzyme which catalyzes the final step of AHBA biosynthesis in the recently discovered aminoshikimate pathway, has been used to identify two separate antibiotic biosynthetic gene clusters in S . collinus . In one of these clusters, analysis of approximately 20 kb of contiguous sequence has revealed both a cluster of six genes presumed to play a role in the AHBA pathway and the beginning of a polyketide synthase (PKS) gene containing an acyl ACP ligase domain . This domain is likely responsible for loading AHBA onto the PKS . This gene cluster also contains chcA, encoding the enzyme 1-cyclohexenylcarbonyl CoA reductase, which is essential for the biosynthesis of the cyclohexanecarboxylic acid moiety of ansatrienin from shikimic acid, and a peptide synthetase . This gene cluster thus seems to control the biosynthesis of ansatrienin, which contains a side chain of N-cyclohexanecarbonyl-d-alanine esterified to the macrocyclic lactam backbone . In the putative naphthomycin biosynthetic gene cluster approximately 13 kb of contiguous sequence has revealed a second set of the genes required for AHBA biosynthesis . In addition the end of a polyketide synthase and a gene putatively involved in termination of the chain extension process, formation of an intramolecular amide bond between the AHBA nitrogen and the carboxyl group of the fully extended polyketide chain, have been identified . Thus, despite commonality in biosynthesis, the ansatrienin and naphthomycin biosynthetic gene clusters show clear organizational differences and carry separate sets of genes for AHBA biosynthesis.

Clin Chem, 1999 Apr, 45(4), 478 - 85
Near-patient test for C-reactive protein in general practice: assessment of clinical, organizational, and economic outcomes; Dahler-Eriksen BS et al.; BACKGROUND: The benefits of near-patient, point-of-care tests have not been fully examined . We have assessed the clinical, organizational, and economic outcomes of implementing a near-patient test for C-reactive protein (CRP) in general practice . METHODS: In a randomized crossover trial during intervention periods, general practitioners (GPs) were allowed to measure CRP within 3 min, using NycoCard(R) CRP . During control periods, they had to mail blood samples for CRP measurements to the hospital laboratory and received test results 24-48 h later . Twenty-nine general practice clinics participated (64 GPs), and 1853 patients were included in the study . Results were evaluated at both the level of participating GPs and the level of included patients . RESULTS: For participating GPs, the overall use of erythrocyte sedimentation rates (ESRs) decreased by 8% (95% confidence interval, 1-14%) during intervention periods, and the number of blood samples mailed to the hospital laboratory decreased by 6% (1-10%) . No reduction in the prescription of antibiotics was seen . The proportion of study patients having a follow-up telephone consultation was reduced from 63% to 53% (P = 0 . 0001), and patients with CRP concentrations >50 mg/L had their antibiotic treatments started earlier when CRP was measured in general practices (P = 0.0161) . CONCLUSION: The implementation of the near-patient CRP test was cost-effective mainly on the basis of a reduction in the use of services from the hospital laboratory by GPs . If the implementation is followed by education and clinical guidelines, opportunities exist for additional reduction in the use of ESR and for a more appropriate use of antibiotics.

Acta Paediatr, 1999 Feb, 88(2), 150 - 3
Free secretory component as a standardization protein for nasopharyngeal specimens from children with upper respiratory tract infection; Heikkinen T et al.; Free secretory component (FSC) has been recommended as a reliable protein for correction of the unknown dilution in tracheal aspirate samples from preterm infants . To investigate whether FSC would also provide a valid standardization protein for samples of nasopharyngeal secretions, this study determined the intersubject variation and the alteration over time in the concentrations of FSC in nasal secretions from 35 children (median age 14 months) who participated in an antibiotic efficacy trial . Nasopharyngeal aspirates were obtained at enrolment and after 2-3 d . FSC in the specimens was quantified by a direct enzyme immunoassay . The concentrations of FSC in the nasal secretions ranged from 0.08 to 189.6 microg ml(-1) (median 12.3 microg ml(-1); the ratio of the highest to the lowest concentrations was 2370, the difference between the 90th and 10th percentile concentrations was 189-fold and the difference between the 75th and 25th percentile values was 26 . FSC concentrations were significantly lower in children aged < or =12 months (median 2.2 microg ml(-1) than in the older children (median 21.5 microg ml(-1); p = 0.035) . Between the first and the follow-up specimens, 65% of the children had > or =2-fold difference in the levels of FSC in the secretions . Because an optimal standardization protein should show minimal variation between individuals and over time, FSC may not be a suitable protein for correction of the unknown dilution of nasopharyngeal specimens from children with upper respiratory tract infection.

Pol Merkuriusz Lek, 1998 Sep, 5(27), 138 - 41
{Variability of pathogenic bacterial flora as a cause of postoperative infection}; Kielar M; The author discussed the results of investigations concerning pathogenic bacterial flora variation causing infection in a surgery ward . Data obtained in the period 1995-1996 were analysed . Covering 118 cases of postoperative infections and 72 cases of primary infections, treated surgically . To establish drug-sensitivity of the bacteria causing infections, the infected samples were taken from all these patients . It was found that different kinds of bacteria caused the postoperative and the primary infections . It was also noted that there was different progress in drug-resistance in each group . The author thing that drug-resistance monitoring in a surgery ward can make antibiotic choice easier in the case of infections, before establishing drug-sensitivity of infection-causing bacteria.

Pol Merkuriusz Lek, 1998 Aug, 5(26), 66 - 8
{The treatment of chronic duodenal ulcer with accompanying Helicobacter pylori infection}; Petsch B et al.; Three hundred seventy four patients with duodenal ulcers and Helicobacter pylori infections were given a four-week treatment of bismuth or ranitidin . In all patients two-week antibiotic therapy were given . Endoscopies with urease tests and histologic examinations were performed before initiation and four weeks after cessation of therapy . Four-week therapy with ranitidini and two-week therapy with amoxicillin and metronidasole is highly effective (89.6%) in duodenal ulcer healing and symptom improvement comparison to bismuth and antibiotic therapy.

Clin Orthop, 1999 Mar, (360), 6 - 13
Introduction to adult posttraumatic osteomyelitis of the tibia; Holtom PD et al.; The tibia is the most frequent site of an open fracture, and treatment of adult posttraumatic osteomyelitis of the tibia represents a significant clinical problem that has been recognized for centuries . Ancient modalities such as immobilization and debridement are still mainstays of therapy, and recent developments such as the use of antibiotics and muscle transfer have helped to improve outcome . Osteomyelitis is classified based on the Cierny-Mader system to provide prognostic and therapeutic information . Open fractures can be classified by the Gustilo system, again providing prognostic and therapeutic data . Gustilo Type III fractures have a high likelihood of having infection develop . Treatment principles include immobilization, thorough debridement, control of infection through antibiotic use, control of dead space, and soft tissue coverage.

Forum (Genova), 1999 Jan-Mar, 9(1), 49 - 57
Haematopoietic growth factors in the treatment of myelodysplastic syndromes; Cazzola M; There are several therapeutic options for myelodysplastic syndrome (MDS) patients but the potentially curative ones are only available for a minority of individuals . At present, in fact, the only two treatments that can prolong survival are allogeneic stem cell transplantation and intensive chemotherapy . The only two haematopoietic growth factors that can be useful in the treatment of selected MDS patients are recombinant human erythropoietin (rHuEpo) and G-CSF . Overall 15 to 20% of patients with MDS respond to rHuEpo treatment but the vast majority of responders are not transfusion-dependent and the doses required to achieve response are > 450 IU/kg per week . Factors predicting response include serum Epo levels <100 mU/ml, female gender and no or low need for transfusion . Recognising potential responders to rHuEpo can be extremely important in individual cases of MDS . G-CSF alone should be used only for short-term treatments . It may be administered to individual patients during an infective episode that does not respond to antibiotic therapy, particularly in the case of fungal infections . In addition, G-CSF may be employed for shortening the length of severe neutropenia following intensive chemotherapy . American and Scandinavian studies have shown that about 40% of MDS patients respond to a combined treatment of rHuEpo with G-CSF with amelioration of anaemia and that response can be maintained for a median duration of 24 months . Using pre-treatment serum Epo levels as a ternary variable (<100, 100-500 or > 500 U/l) and red blood cell transfusion need as a binary variable (<2 or > or =2 units per month), a predictive score for erythroid response to G-CSF plus rHuEpo can be obtained . This score can identify patients with a high probability of erythroid responses (about 75%) . Due to the inadequacies of all current treatment modalities, participation in clinical trials should always be encouragedPublication Types:

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