Aliment Pharmacol Ther, 2003 Oct 15, 18(8), 847 - 51 Gastric acid-suppressive therapy and community-acquired respiratory infections; Laheij RJ et al.; BACKGROUND: Bacteria and viruses have been detected in the stomach of patients during acid-suppressive therapy . AIM: To investigate whether subjects using acid-suppressive drugs more often develop community-acquired respiratory infections when compared to those who do not use acid-suppressive drugs . METHODS: 700 study subjects were recruited during a single week in December 2002 . Information on the prevalence of clinical manifestations of infections and complications in the preceding month was assessed by questionnaire . Furthermore, subjects were asked to report antibiotic therapy and physician visits related to possible infection . RESULTS: Questionnaires were returned by 405 subjects (58%) . Consumption of acid-suppressive drugs was reported by 91 individuals, of whom 79 used proton-pump inhibitors (20%) and 12 H2-receptor antagonists (3%) . Overall, 101 (25%) responders reported clinical manifestations of respiratory infection in the preceding month . Subjects using acid-suppressive drugs were 2.34 times {95% confidence interval (CI) 1.4-4.1} more likely to have clinical manifestations of infection than individuals not using acid-suppressive drugs . Subjects using acid-suppressive drugs visited a physician 3.72 times more often (95% CI 2.1-6.8) for an infection and received antibiotic therapy 4.19 times more often (95% CI 2.2-8.1) in comparison to individuals not using acid-suppressive drugs . CONCLUSIONS: Subjects using acid-suppressive drugs more often reported community-acquired respiratory infections in comparison to those who did not use acid-suppressive drugs. Aliment Pharmacol Ther, 2003 Oct 15, 18(8), 791 - 7 Second-line treatment for failure to eradicate Helicobacter pylori: a randomized trial comparing four treatment strategies; Lamouliatte H et al.; AIM: To compare the efficacy of different regimens in patients in whom previous Helicobacter pylori eradication therapy has failed . METHODS: In this study named StratHegy patients (n=287) were randomized to receive one of three empirical triple therapy regimens or a strategy based on antibiotic susceptibility . The empirical regimens were omeprazole, 20 mg b.d., plus amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d., for 7 days (OAC7), clarithromycin, 500 mg b.d., for 14 days (OAC14) or metronidazole, 500 mg b.d., for 14 days (OAM14) . In the susceptibility-based strategy, patients with clarithromycin-susceptible strains received OAC14, whilst the others received OAM14 . The 13C-urea breath test was performed before randomization and 4-5 weeks after eradication therapy . RESULTS : In the intention-to-treat analysis, the eradication rates for empirical therapies were as follows: OAC7, 47.4% (27/57); OAC14, 34.5% (20/58); OAM14, 63.2% (36/57); it was 74.3% (84/113) for the susceptibility-based treatment (P<0.01 when compared with OAC7 and OAC14) . In patients receiving clarithromycin, the eradication rates were 80% for clarithromycin-susceptible strains and 16% for clarithromycin-resistant strains; in patients receiving OAM14, the eradication rates were 81% for metronidazole-susceptible strains and 59% for metronidazole-resistant strains . CONCLUSIONS: Eradication rates of approximately 75% can be achieved with second-line triple therapy based on antibiotic susceptibility testing . If susceptibility testing is not available, OAM14 is an appropriate alternative. Org Lett, 2003 Oct 16, 5(21), 3883 - 5 Stereoselective construction of cis-2,6-disubstituted tetrahydropyrans via the reductive etherification of delta-trialkylsilyloxy substituted ketones: total synthesis of (-)-centrolobine; Evans PA et al.; {reaction: see text} The stereoselective intramolecular reductive etherification of delta-trialkylsilyloxy substituted ketones with catalytic bismuth tribromide and triethylsilane provides a convenient method for the construction of cis-2,6-disubstituted tetrahydropyrans . This method was highlighted in the key step of an expeditious total synthesis of the antibiotic, (-)-centrolobine. Curr Cancer Drug Targets, 2003 Oct, 3(5), 343 - 7 The C-terminal half of heat shock protein 90 represents a second site for pharmacologic intervention in chaperone function; Marcu MG et al.; The molecular chaperone heat shock protein 90 (Hsp90) is required for stability and function of multiple mutated, chimeric, and over-expressed signaling proteins that promote cancer cell growth and/or survival . It is also critical for the function of many normally expressed proteins, including protein kinases, steroid receptors and other transcription factors, and it may protect the cell from incapacitating or deleterious mutations . The recent identification of a nucleotide binding pocket within the first 220 amino acids of the protein, together with the discovery that at least two structurally distinct classes of antibiotic can replace nucleotide at this site and alter chaperone activity, has deservedly focused attention on Hsp90's aminoterminus as an important regulator of function . However, data continue to accumulate pointing to the C-terminal half of the chaperone as an equally important regulator of activity, and small molecules that bind to this portion of Hsp90 have been identified. Veterinary Clin North Am Exot Anim Pract, 2003 Sep, 6(3), 565 - 70 Oral disorders of exotic ungulates; Knightly F et al.; There are many species classified as ungulates that possess a large variety of dental formulae and dental adaptations . Despite the diversity found within the ungulate group, the list of dental abnormalities remains short . Regardless of the contributing factors, cases of aveolitis accompanied by osteomyelitis ("lumpy jaw") occur more frequently than some of the other dental problems that are encountered in these species (fractures of tusks/canines, malocclusion, eruption cysts) . Commonly, treatment of "lumpy jaw" requires exodontia with additional antibiotic therapy using a drug that is appropriate for the type of infection and the species of animal . Regardless of the dental abnormality, anesthetic, diagnostic, and treatment considerations typically provide the greatest challenge to the clinician in these cases. Surg Clin North Am, 2003 Oct, 83(5), 1255 - 78 Complications of open groin hernia repairs; Stephenson BM; As large numbers of patients undergo hernioplasty each year the surgical technique should be a simple one . The results obtained by general surgeons using various open, tension-free techniques, irrespective of the anesthetic used, are excellent and appear to approach those of specialists . This can not be said for laparoscopic hernioplasty, which has a well-known learning curve, is more expensive and is not without complications, some of which may be serious or life threatening . Although proper training in laparoscopic techniques is essential, the same applies to open repair with mesh . Surgical residents should be taught open-mesh repairs under local anesthesia before embarking on training in laparoscopic techniques if they show interest in pursuing this approach . Indeed, we may soon be faced with an increasing number of patients who are not fit for a general anesthetic . Not all hernias need be repaired by specialists and visiting centers with experience in the use of different prosthetic devices allows you to draw your own conclusions . Finally, when consulting a patient with an inguinal hernia, primary or recurrent, the surgeon should pose the question "which combination of anesthetic and hernia repair is the safest and best for my patient?" Local anesthesia with appropriate analgesia and sedation is the safest of all techniques and is suitable for most if not all open repairs . Using this approach, any type of open-mesh repair makes the ideal combination and all can be safely carried out on an ambulatory basis . Attention to surgical technique is paramount, and given the number of hernias repaired annually, it is pertinent to recall the words of Wakely, who said "A surgeon can do more for the community by operating on hernia cases, and seeing that his recurrence rate is lower, than he can by operating on cases of malignant disease." Surg Clin North Am, 2003 Oct, 83(5), 1119 - 39 The Kugel repair for groin hernias; Kugel RD; The Kugel repair is a minimally invasive but nonlaparoscopic preperitoneal hernia repair . It has certain advantages over other repairs, but will require a little additional effort initially to learn the repair and the associated anatomy encountered in this approach . This anatomy has not, historically, been well taught in medical schools . This repair is an attempt to achieve the fastest recovery possible after groin hernia surgery while assuring a very low risk of recurrence. Ann Allergy Asthma Immunol, 2003 Sep, 91(3), 314 - 7 Hepatic metabisulfite sensitivity in a patient with sclerosing cholangitis; Stormont JM et al.; BACKGROUND: Primary sclerosing cholangitis is an uncommon chronic cholestatic liver disease with a poor prognosis in symptomatic cases . Genetic and immunologic alterations have been identified, and many possible etiologies have been entertained . Most treatments have limited benefit, and primary sclerosing cholangitis is a common cause for liver transplantation . OBJECTIVE: To describe a patient with documented primary sclerosing cholangitis associated with chronic ulcerative colitis, who developed hepatic toxicity following ingestion of metabisulfite . RESULTS: A placebo-controlled oral challenge suggested metabisulfite hypersensitivity with liver toxicity . He was treated with cobalamin (to prevent sulfite toxicity), low-sulfite diet, steroids, and antibiotics and has had an unusually benign course for 19 years . CONCLUSIONS: The hypersensitivity to oral metabisulfite in our patient appeared to be a significant trigger to flare-ups of his disease . Controlling the response to metabisulfite (along with recurrent antibiotic and steroid therapy) may have contributed significantly to the remarkably good outcome in this patient. Zentralbl Chir, 2003 Sep, 128(9), 726 - 33 {Borderline amputations in diabetics--open questions and critical evaluation}; Rumenapf G; Minor amputations are frequently performed in neuroischemic or neuropathic lesions of the diabetic foot . In German-speaking countries, the term "Grenzzonenamputation" was created to describe the combination of minor amputation exactly in the border zone to vital tissues, necrosectomy and debridement . For early and optimal rehabilitation, as much vital tissue as possible should be conserved, especially the skeletal structures of the foot . "Grenzzonenamputationen" are of utmost importance for the prevention of ascending infections, and they reduce the duration of clinical and outpatient treatment . "Grenzzonenamputationen" should be performed only by experienced surgeons and if the arterial perfusion is sufficient . They should be as tissue-sparing as possible, and structured interdisciplinary postoperative care is mandatory . Controversial opinions exist with respect to the use of tourniquets, conservation or resection of cartilage and sesamoids, open amputation or primary closure of the wound, interdigital spacer function of toes, aseptic proximal transection of tendons, postoperative wound care, and antibiotic therapy . In view of these controversies, the most important distal minor amputations are described and discussed, with special regard to the habitual surgical way of thinking. Scand J Prim Health Care, 2003 Sep, 21(3), 171 - 7 Characteristics of frequent attenders in different age and sex groups in primary health care; Bergh H et al.; OBJECTIVE: To compare frequent attenders in different age and sex groups with a control group according to characteristics and use of primary health care . DESIGN: Descriptive study of medical records . SETTING: Primary health care centre . SUBJECTS: 341 frequent attenders, divided by age and sex, were compared with 1025 controls from the same area . MAIN OUTCOME MEASURES: Consultation rate, diagnoses, prescribed medicine, referrals and certificates of illness during one year . RESULTS: Frequent attenders constituted 3.3% of the population but accounted for 25% of all visits to the GP and 44% of all illness certificates allocated . They were given more antibiotic prescriptions and consulted the GP more often for most medical problems . Frequent attenders had a morbidity, with a preponderance of infections at a young age, musculoskeletal and respiratory problems in middle age, and, among the oldest, circulatory, endocrine and musculoskeletal diseases . CONCLUSION: Frequent attenders had a morbidity within different ages similar to that of the controls, but also a higher consulting frequency for most medical problems and a significantly higher consumption of antibiotics . Are frequent attenders more vulnerable individuals and more prone to all kinds of diseases, or do they just consult more often for the usual medical problems? Nihon Kokyuki Gakkai Zasshi, 2003 Sep, 41(9), 636 - 40 {A case of pulmonary thromboembolism due to idiopathic thrombosis of inferior vena cava, which was initially misdiagnosed as pneumonia}; Kaneko T et al.; We report a case of a 73-year-old man with pulmonary embolism due to idiopathic thrombosis of the inferior vena cava . He was referred to our hospital because of a fever and cough of 2 weeks' duration despite treatment with an oral antibiotic . Chest radiography on the first visit showed an infiltrate in the right middle lung field . He was diagnosed as having pneumonia and admitted to our hospital for treatment . Following administration of intravenous antibiotics, his symptoms disappeared and the chest radiography findings improved . The abdominal CT obtained in an attempt to visualize the cause of liver dysfunction serendipitously revealed thrombosis of the inferior vena cava, which was suspected to have caused the pulmonary embolism . A subsequent lung perfusion scan revealed marked perfusion defects in the right middle and lower lobes . Chest CT revealed an embolus located in the right pulmonary artery . Since thrombolytic therapy was not effective, the placement of a filter in the inferior vena cava was performed to prevent the recurrence of pulmonary embolism . The patient has been asymptomatic without recurrence of the disease since the filter insertion. Masui, 2003 Sep, 52(9), 996 - 9 {Iliopsoas abscess accompanied by epidural abscess--a case report}; Fukushige T et al.; A 55-year-old man was admitted to a hospital with pain of the low back as well as the left leg, and fever . He was suspected of suffering from the lumbar disc herniation because of the presence of Lasegue's sign on the first physical examination . Abdominal computed tomography, however, revealed the swelling of the left iliopsoas muscle . Iliopsoas abscess accompanied epidural abscess was confirmed by subsequent magnetic resonance imaging (MRI) . Antibiotic therapy was started for the successive 8 days . The fever resolved, but the pain persisted . The abscess extending from the iliopsoas muscle to the epidural space was still seen on the MRI 20 days after the completion of the antibiotic therapy, and he still complained of the pain of his low back and left leg . Therefore, we conducted epidural puncture under fluoroscopic guidance . Approximately 3 ml of pus was aspirated from the epidural space . Then, his complains decreased remarkably . Iliopsoas abscess should be taken into account in case of a patient with pain on the low back and leg and also inflammatory signs such as fever and leucocytosis. Transplant Proc, 2003 Sep, 35(6), 2202 - 4 Pneumonia in kidney allograft recipients; Pazik J et al.; Infectious complications, including pneumonia, remain one of the leading causes of morbidity and mortality in kidney allograft recipients . The aim of the study was to evaluate the relationship between pneumonia occurrence and treatment duration and recipient age, cause of native kidney insufficiency, dialysis duration, time between transplantation and onset, HLA matching, PRA immunosuppressive protocol, acute rejection incidence and treatment, kidney function at the pneumonia onset, as well as presence of comorbid conditions . One hundred and twenty pneumonia cases occurred in kidney allograft recipients transplanted between 1991 and 2000 with 12 to 120 months follow-up . Twenty five percentage of pneumonia episodes were diagnosed during the first posttransplant month, 25% between 2 and 6 months, and 25% at 0.5 to 3 years . Treatment duration measured from pneumonia onset to the study endpoint of recovery, which was defined as antibiotic withdrawal, show 50% of patient we cured after 15 days and 75% after 24 days of treatment . The risk of prolonged pneumonia treatment was associated with: second versus first kidney transplantation with RR = 2.3 (P <.02) and medians of treated time 28 versus 15 days; as well as serum creatinine level above 2 mg/dL (RR = 1.4; P <.098) . Exposure to enhanced-potency immunosuppressive protocols including induction therapy with mono- or polyclonal antibodies increased the RR = 1.65 (P <.02), and lengthened the time to 18 versus 14 days . Maintenance immunosuppression with agents other than cyclosporine also enhanced the risk . (RR = 2.18; P <.068). Curr Cancer Drug Targets, 2003 Oct, 3(5), 359 - 69 Development of radicicol analogues; Soga S et al.; Radicicol, a macrocyclic antibiotic produced by fungi, was originally isolated many years ago, and was described as tyrosine kinase inhibitor . We also rediscovered radicicol as an inhibitor of signal transduction of oncogene products, such as K-ras and v-Src, using yeast and mammalian cell-based assays . In a study of mechanisms of action, it was revealed that radicicol depletes the Hsp90 client signaling molecules in cells, and thus inhibit the signal transduction pathway . In addition, direct binding of radicicol to the N-terminal ATP/ADP binding site of Hsp90 was shown, and thus radicicol has been recognized as a structurally unique antibiotic that binds and inhibits the molecular chaperone Hsp90 . Although radicicol itself has little or no activity in animals because of instability in animals, its oxime derivatives showed potent antitumor activities against human tumor xenograft models . Hsp90 client proteins were depleted and apoptosis was induced in the tumor specimen treated with radicicol oxime derivatives . Taken together, these results suggest that the antitumor activity of radicicol oxime derivatives is mediated by binding to Hsp90 and destabilization of Hsp90 client proteins in the tumor . Among Hsp90 clients, we focused on ErbB2 and Bcr-Abl as examples of important targets of Hsp90 inhibitors . Radicicol oxime showed potent antitumor activity against ER negative/ErbB2 overexpressing breast cancer and Bcr-Abl expressing CML . Putative mechanisms of action and future directions of radicicol oxime against these kinds of tumor are discussed. Biochemistry, 2003 Oct 14, 42(40), 11577 - 86 Biochemical and spectroscopic studies on (S)-2-hydroxypropylphosphonic acid epoxidase: a novel mononuclear non-heme iron enzyme; Liu P et al.; The last step of the biosynthesis of fosfomycin, a clinically useful antibiotic, is the conversion of (S)-2-hydroxypropylphosphonic acid (HPP) to fosfomycin . Since the ring oxygen in fosfomycin has been shown in earlier feeding experiments to be derived from the hydroxyl group of HPP, this oxirane formation reaction is effectively a dehydrogenation process . To study this unique C-O bond formation step, we have overexpressed and purified the desired HPP epoxidase . Results reported herein provided initial biochemical evidence revealing that HPP epoxidase is an iron-dependent enzyme and that both NAD(P)H and a flavin or flavoprotein reductase are required for its activity . The 2 K EPR spectrum of oxidized iron-reconstituted fosfomycin epoxidase reveals resonances typical of S = (5)/(2) Fe(III) centers in at least two environments . Addition of HPP causes a redistribution with the appearance of at least two additional species, showing that the iron environment is perturbed . Exposure of this sample to NO elicits no changes, showing that the iron is nearly all in the Fe(III) state . However, addition of NO to the Fe(II) reconstituted enzyme that has not been exposed to O(2) yields an intense EPR spectrum typical of an S = (3)/(2) Fe(II)-NO complex . This complex is also heterogeneous, but addition of substrate converts it to a single, homogeneous S = (3)/(2) species with a new EPR spectrum, suggesting that substrate binds to or near the iron, thereby organizing the center . The fact that NO binds to the ferrous center suggests O(2) can also bind at this site as part of the catalytic cycle . Using purified epoxidase and (18)O isotopic labeled HPP, the retention of the hydroxyl oxygen of HPP in fosfomycin was demonstrated . While ether ring formation as a result of dehydrogenation of a secondary alcohol has precedence in the literature, these catalyses require alpha-ketoglutarate for activity . In contrast, HPP epoxidase is alpha-ketoglutarate independent . Thus, the cyclization of HPP to fosfomycin clearly represents an intriguing conversion beyond the scope entailed by common biological epoxidation and C-O bond formation. Gastrointest Endosc, 2003 Sep, 58(3), 362 - 8 Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA; Wildi SM et al.; BACKGROUND: Benign mediastinal cysts, which account for approximately 20% of mediastinal masses, may be diagnostic challenges . Information regarding the use of EUS and EUS-guided FNA in this setting is limited . The aim of this study was to demonstrate the value and potential risks of EUS and EUS-FNA in the diagnosis of mediastinal foregut cysts . METHODS: The EUS database of a single tertiary referral center was reviewed for the diagnosis of benign mediastinal cysts . Twenty patients were identified who underwent 23 EUS examinations for suspected mediastinal cysts (n = 4), for follow-up of a known cyst (n = 3), or for a mediastinal mass of unknown origin (n = 16) . RESULTS: In 19 patients, the definite diagnosis of a mediastinal cyst was established by EUS . Twelve cysts appeared anechoic, 6 were hypoechoic, and one anechoic cyst contained small echoic foci . CT (n = 17) or magnetic resonance imaging (n = 1) was performed in 18 cases; only 4 of these were diagnostic of a cyst . In 3 cases, the cyst contents were aspirated by EUS-FNA . In a fourth case, a solid-appearing duplication cyst, misdiagnosed by EUS, was sampled with FNA and core biopsy . This patient developed severe sepsis secondary to mediastinitis 4 days later . Thoracotomy revealed an infected bronchogenic cyst . CONCLUSIONS: EUS provides a minimally invasive approach to the diagnosis of benign mediastinal cysts and may be more accurate than CT or other imaging modalities . Aspiration of suspected cysts should be undertaken with caution, given the risk of infection. Am J Obstet Gynecol, 2003 Sep, 189(3), 794 - 8 Prolonged latency after preterm premature rupture of membranes: an evaluation of histologic condition and intracranial ultrasonic abnormality in the neonate born at <28 weeks of gestation; McElrath TF et al.; OBJECTIVE: The purpose of this study was to evaluate whether infants who were delivered at <28 weeks of gestation after prolonged latency in pregnancies that were complicated by preterm premature rupture of membranes are at increased risk of histologic chorioamnionitis and intracranial ultrasound abnormalities . STUDY DESIGN: A retrospective cohort analysis of 430 singleton infants born at <28 weeks of gestation in five hospitals (January 1991 through December 1993) with at least one of three protocol cranial scans read by a consensus committee and with placental pathologic evidence . Outcome variables were placental (histologic chorioamnionitis, fetal vasculitis) and neonatal (intraventricular hemorrhage, echolucencies, ventriculomegaly) . Latency was divided into five intervals, and outcomes in the longer four intervals were compared with those in infants who were delivered at <1 hour after membrane rupture . Each outcome-latency relationship was evaluated in a logistic model that was controlled for confounders . RESULTS: Odds ratios and CIs for each latency interval that was controlled for confounders that included gestational age, maternal race, antenatal steroid and antibiotic administration, and delivery mode show a statistically significant increase in the risk of histologic chorioamnionitis and fetal vasculitis . Models for intraventricular hemorrhage, ventriculomegaly, and echolucencies failed to demonstrate significant differences with increasing latency . CONCLUSIONS: Ascending transcervical infection after preterm premature rupture of membranes is documented by the increasing odds ratios of placental inflammation . The odds of ultrasonically detectable brain abnormalities, however, did not increase with increasing latency. Chembiochem, 2003 Oct 6, 4(10), 1078 - 88 The molecular basis for A-site mutations conferring aminoglycoside resistance: relationship between ribosomal susceptibility and X-ray crystal structures; Pfister P et al.; Aminoglycoside antibiotics target the 16S ribosomal RNA (rRNA) bacterial A site and induce misreading of the genetic code . Point mutations of the ribosomal A site may confer resistance to aminoglycoside antibiotics . The influence of bacterial mutations (introduced by site-directed mutagenesis) on ribosomal drug susceptibility was investigated in vivo by determination of minimal inhibitory concentrations . To determine the origin of the various resistance phenotypes at a molecular level, the in vivo results were compared with the previously published crystal structures of paromomycin, tobramycin, and geneticin bound to oligonucleotides containing the minimal A site . Two regions appear crucial for binding in the A site: the single adenine residue at position 1408 and the non-Watson-Crick U1406.U1495 pair . The effects of mutations at those positions are modulated by the nature of the substituent at position 6' (either hydroxy or ammonium group) on ring I, by the number of positive charges on the antibiotic, and by the linkage between rings I and III (either 4,5 or 4,6) . In particular, the analysis demonstrates: 1) that the C1409-G1491 to A1409-U1491 polymorphism (observed in 15 % of bacteria) is not associated with resistance, which indicates that it does not affect the stacking of ring I on residue 1491, 2) that the high-level resistance to 6'-NH3+ aminoglycosides exhibited by the A1408G mutation most probably results from the inability of ring I forming a pseudo base pair with G1408, which prevents its insertion inside the A site helix, and 3) that mutations of the uracil residues forming the U1406.U1495 pair either to cytosine or to adenine residues mostly confer low to moderate levels of drug resistance, whereas the U1406C/U1495A double mutation confers high-level resistance (except for neomycin), which suggests that aminoglycoside binding to the wild-type A site and its functional consequences strongly depend on a particular geometry of the U1406.U1495 pair . The relationships between the resistance phenotypes observed in vivo and the interactions described at the molecular level define the biological importance of the different structural interactions observed by X-ray crystallography studies. Chembiochem, 2003 Oct 6, 4(10), 1057 - 65 Structural investigation of a high-affinity MnII binding site in the hammerhead ribozyme by EPR spectroscopy and DFT calculations . Effects of neomycin B on metal-ion binding; Schiemann O et al.; Electron paramagnetic resonance spectroscopy and density functional theory methods were used to study the structure of a single, high-affinity Mn(II) binding site in the hammerhead ribozyme . This binding site exhibits a dissociation constant Ke of 4.4 microM in buffer solutions containing 1 M NaCl, as shown by titrations monitored by continuous wave (cw) EPR . A combination of electron spin echo envelope modulation (ESEEM) and hyperfine sublevel correlation (HYSCORE) experiments revealed that the paramagnetic manganese(II) ion in this binding site is coupled to a single nitrogen atom with a quadrupole coupling constant kappa of 0.7 MHz, an asymmetry parameter eta of 0.4, and an isotropic hyperfine coupling constant of Aiso(14N)=2.3 MHz . All three EPR parameters are sensitive to the arrangement of the Mn(II) ligand sphere and can therefore be used to determine the structure of the binding site . A possible location for this binding site may be at the G10.1, A9 site found to be occupied by Mn(II) in crystals (MacKay et al., Nature 1994, 372, 68 and Scott et al., Science 1996, 274, 2065) . To determine whether the structure of the binding site is the same in frozen solution, we performed DFT calculations for the EPR parameters, based on the structure of the Mn(II) site in the crystal . Computations with the BHPW91 density function in combination with a 9s7p4d basis set for the manganese(II) center and the Iglo-II basis set for all other atoms yielded values of kappa(14N)=+0.80 MHz, eta=0.324, and Aiso(14N)=+2.7 MHz, in excellent agreement with the experimentally obtained EPR parameters, which suggests that the binding site found in the crystal and in frozen solution are the same . In addition, we demonstrated by EPR that Mn(II) is released from this site upon binding of the aminoglycoside antibiotic neomycin B (Kd=1.2 microM) to the hammerhead ribozyme . Neomycin B has previously been shown to inhibit the catalytic activity of this ribozyme (Uhlenbeck et al., Biochemistry 1995, 34, 11 186). Int J Artif Organs, 2003 Aug, 26(8), 698 - 714 Peritoneal catheter exit-site infections: predisposing factors, prevention and treatment; Thodis E et al.; Catheter-related infections, exit-site-tunnel infections and peritonitis remain the Achilles heel of peritoneal dialysis . Although the overall incidence of peritoneal-dialysis-related infectious complications has been reduced since the introduction of the Y-set and double bag system, approximately one-fifth of peritonitis episodes are associated with catheter exit-site and tunnel infections . Since its development in 1968, the Tenckhoff catheter has become one of the most widely used peritoneal catheters, and many have proposed that a number of modifications have made it a better choice . Controversies concerning the effect on exit-site infections of catheter(s) with one or two cuffs, with straight, coiled, Swan-Neck, or other modifications led to the randomized controlled studies that are reviewed in this paper . Several studies have confirmed that mupirocin, applied at the exit-site as part of regular exit-site care, reduces the risk of S . aureus exit-site and tunnel infections . Recently, the emergence on a world-wide basis of mupirocin-resistant S . aureus (MuRSA) in peritoneal dialysis patients has brought this prophylactic strategy into question . However the low frequency of resistant organisms after four years of mupirocin prophylaxis suggests that we can continue its use with annual surveillance . Once established, exit-site infections may respond to appropriate treatment, but if not the only option may be catheter removal and replacement . Although peritonitis risk has decreased over the past decade, mainly due to improvements in connection technology, exit-site and tunnel infections have not . An exit-site infection that does not respond to treatment may lead to tunnel infection and to persistent peritonitis, which may require catheter removal and occasionally discontinuation of the peritoneal dialysis . Therefore it is important to be familiar with these factors that predispose to exit-site infection and to know how to prevent and to treat such infections . This review will discuss factors that predispose to catheter-related exit-site infections, techniques of exit-site care, and ways to prevent exit-site infection, with emphasis on S . aureus infections and their treatment. Acta Paediatr Taiwan, 2003 May-Jun, 44(3), 135 - 9 Percutaneous endoscopic gastrostomy in children: 15 cases experience; Yeh TC et al.; For long-term tube feeding in children, percutaneous endoscopic gastrostomy (PEG) has the advantages of a short surgical time, early feeding following surgery, and lower rate of complications . From July 2000 to September 2002, we enrolled fifteen children (mean age: 8.2 years old) who underwent PEG placement for long-term nutritional support . Their underlying diseases included mucopolysaccharidosis (MPS) type II severe form, mitochondrial disease, Ehlers-Danlos syndrome associated with Robin sequence, spinal muscular atrophy (SMA) type II, nesidioblastosis, neurofibromatosis and other neurological disorders . We assessed the complications and outcome in these patients after PEG placement . There were no difficulties in PEG tube-feeding after procedure . One patient had a wound infection at the insertion site which required parenteral antibiotic therapy . Symptomatic gastroesophageal reflux (GER) occurred in two patients and was controlled with medication . One patient developed a gastrocutaneous fistula, requiring surgical removal of the PEG tube . One patient underwent laparoscopic gastrojejunostomy and Nissen fundoplication for persistent vomiting . Two patients with mitochondrial disease expired . The other eleven devices have continued to function on follow-up . Placement of a PEG is a simple, feasible procedure for children with swallowing difficulty who require long-term nutritional support . Although complications may sometimes occur, in our experience many can be managed conservatively. Neurosurgery, 2003 Oct, 53(4), 893 - 7; discussion 897-8 Conservative neurosurgical management of intracranial epidural abscesses in children; Heran NS et al.; OBJECTIVE: Traditional management of epidural abscesses caused by sinusitis in children involves neurosurgical drainage . With better techniques to drain affected sinuses, to identify causative organisms, and to guide medical therapy, some pediatric epidural intracranial abscesses may be treated effectively with sinus drainage and antibiotics, without an intracranial procedure . METHODS: Charts and computed tomographic scans of children with isolated intracranial epidural abscess associated with sinusitis who were treated in a pediatric hospital were reviewed retrospectively . RESULTS: Eight patients were treated between 1982 and 2002 . All patients received antibiotic therapy appropriate to the causative organism(s) . Four patients treated before mid-1997 had an intracranial procedure additionally (operative group, Group 1), and four patients treated thereafter did not (conservative group, Group 2) . Abscesses had a mean size of 3 x 3 x 1 cm (length x width x depth) in both groups . All patients experienced clinical and radiographic resolution of the infection with treatment . In Group 1, neurosurgical management consisted of burr hole drainage in two patients and craniotomy in two patients . Extranasal otorhinolaryngological procedures for sinus drainage were performed in two patients . In Group 2, endonasal procedures were used in three patients for paranasal sinus infections to effect drainage and obtain specimens for culture . A radical mastoidectomy was required in the single patient with mastoiditis . Although two of four patients initially demonstrated transient worsening of headaches, all patients subsequently improved rapidly after the first week of treatment . Computed tomographic follow-up revealed minimal or no enlargement of the abscess or mass effect at 1 week, decrease or stable size at 2 weeks, and resolution by 6 weeks . CONCLUSION: Sinus-related intracranial epidural abscesses in children may be managed without neurosurgical procedures in the setting of adequate sinus drainage, appropriate antibiotic therapy, and minimal extradural mass effect from the abscess . Symptomatic worsening without significant increase in mass effect during the first week of therapy is not necessarily an indication for an intracranial drainage procedure. Expert Opin Investig Drugs, 2003 Oct, 12(10), 1609 - 14 The Lyme Wars: time to listen; Stricker RB et al.; Lyme disease represents a public health threat of major proportions . The murky science and acrimonious politics of Lyme disease have created barriers to reliable diagnosis and effective treatment of this protean illness . Two major clinical problems with the disease are the absence of a therapeutic end point in treating Borrelia burgdorferi, the spirochetal agent of Lyme disease, and the presence of tick-borne co-infections, such as babesiosis, anaplasmosis and bartonellosis, that may complicate the course of the illness . From a pathophysiological standpoint, the affinity of B . burgdorferi for multiple cell types and the presence of non-replicating forms of the spirochete have contributed to persistent infection and failure of simple antibiotic regimens . Newer approaches to the treatment of Lyme disease should take into account its clinical complexity in co-infected patients and the possible need for prolonged combination therapy in patients with persistent symptoms of this potentially debilitating illness . The risk and prevention of human transmission of Lyme disease merit further study. Gan To Kagaku Ryoho, 2003 Sep, 30(9), 1365 - 71 {Evidence-based management of neutropenia and fever}; Ishiguro H et al.; Neutropenia and related fever are the most frequently observed toxicities associated with chemotherapy use . In this review, the current approaches based on various Japanese and American medical societies' guidelines in managing these toxicities are examined . First, the therapeutic and prophylactic use of G-CSF is explored . Clinical efficacy of G-CSF as exemplified by the results of a randomized comparative trial conducted based on the latest guidelines of the American as well as Japan Societies of Clinical Oncology is demonstrated . In addition, the difference in clinical efficacy of the therapeutic use of G-CSF with the presence or absence of fever is assessed . Lastly, the current approaches based on the latest guidelines of the American Society of Infectious Diseases and National Comprehensive Cancer Network (NCCN) to manage patients with febrile neutropenia are also reviewed . Specifically, infection work-ups, antibiotics selection, proper methods of usage, and follow-up methods from these guidelines are delineated . It is hoped that this report will provide readers with the most up-to-date information in managing patients with these toxicities. Vnitr Lek, 2003 Aug, 49(8), 630 - 6 {Puncture aspiration using ultrasound guidance in the treatment of abscesses and other purulent foci in the liver, pancreas and kidneys}; Martinek A et al.; The authors deal with the problem of application of a therapeutic fine needle aspiration puncture in abscesses and other purulent foci in organs of abdominal cavity and retroperitoneum . The treatment using this method under continuing antibiotic therapy has been used in 60 patients (40 men, 20 women), 25 of them suffering from liver abscesses, 28 other from purulent foci of pancreas and seven patients from purulent foci of the kidney . In most patients there were solitary foci (43 persons) . The total volume of the evacuated pus was higher than 20 ml in most patients (52), being even more than 100 ml in 2 patients . No relation ship was found among the number of foci, their volume and efficiency of the treatment . The average number of punctures until the abscesses and other purulent foci were healed up was 2.76 in the liver, 2.5 in pancreas and 1.1 in the kidney . The efficiency of therapy was higher in liver abscesses (96%), in purulent foci of pancreas (82%) and lower in the kidney abscesses (57%) . The higher efficiency in the purulent foci of pancreas was probably influenced by predominant representation by infected pseudocysts in this group . The lower average number of punctures until the abscesses were healed up and the lower success in the kidney were influenced by a more radical approach of urologists who, having made the first evacuation puncture, performed a radical operation intervention . The complications were encountered in 9.5% of all punctures, being always insignificant . The results obtained demonstrated the contribution of aimed therapeutic aspiration puncture in the therapy of purulent foci of parenchymal organs of abdominal cavity and retroperitoneum as compared with surgical treatment . The advantage of the applied method in the therapy of purulent foci of the liver and pancreas may be seen in the higher success rate, low invasiveness and a low risk of complications together with a low financial cost and wide availability. J Pediatr, 2003 Sep, 143(3), 377 - 85 A randomized, placebo-controlled trial of the effect of antihistamine or corticosteroid treatment in acute otitis media; Chonmaitree T et al.; OBJECTIVES: To determine whether the adjunctive drugs antihistamine and corticosteroid improve immediate and long-term outcomes of acute otitis media (AOM) . STUDY DESIGN: Children with AOM (3 mos-6 y) were enrolled in a randomized, double-blind, placebo-controlled trial . All 179 children received one dose of intramuscular ceftriaxone and were assigned to receive either chlorpheniramine maleate (0.35 mg/kg/d) and/or prednisolone (2 mg/kg/day) or placebo for 5 days . Main outcome measures were rate of treatment failure during the first 2 weeks, duration of middle ear effusion, and rate of recurrences of AOM to 6 months . RESULTS: Clinical outcomes and recurrence rates did not differ significantly with treatment . Children who received antihistamine alone had significantly longer duration of middle ear effusion (median, 73 days) than subjects in other treatment groups (median, 23 to 36 days, P=.04) . Temporary normalization of tympanometric findings on day 5 occurred more frequently in the corticosteroid-treated group (P=.04) . CONCLUSIONS: Five-day treatment with antihistamine or corticosteroid, in addition to antibiotic, did not improve AOM outcomes . Antihistamine use during an acute episode of OM should be avoided, since the drug may prolong the duration of middle ear effusion . The efficacy of 7- to 10-day treatment of AOM with corticosteroid, in addition to antibiotic, deserves further investigation. J Biosci, 2003 Sep, 28(5), 597 - 604 Bioprospecting the lat gene in soil samples; Dharwadkar A et al.; Twenty soil communities from the northeastern forests (Assam) and the Western Ghats (Maharashtra) were screened for the presence of the lysine aminotransferase (lat) gene from Nocardia . Hybridization probes and primers were synthesized in accordance with the reported sequence of the Nocardia lat gene from GenBank (number: G1 49355) . Seven positives were obtained from the 20 soils . Six of the seven positive were from the Western Ghats and one from the northeast Assam forests . Eighteen actinomycete isolates from the 7 positive soils showed the presence of the lat gene . Only 9 isolates actually produced an antibiotic . These results are discussed. Vet Microbiol, 2003 Oct 8, 96(1), 53 - 67 Effect of steroidal and non-steroidal anti-inflammatory drugs in combination with long-acting oxytetracycline on non-specific immunity of calves suffering from enzootic bronchopneumonia; Bednarek D et al.; The aim of this paper was to compare the effect of flumethasone and meloxicam in combination with oxytetracycline on clinical and immunological parameters of calves suffering from enzootic bronchopneumonia . The study was performed on 30 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided randomly into three equal groups and, respectively, treated with-Group I: oxytetracycline and meloxicam; Group II: oxytetracycline and flumethasone; Group III (control): oxytetracycline only . Treatment of calves with the combination of oxytetracycline and meloxicam (Group I) caused a significantly faster, in comparison to other groups, improvement in the clinical illness index score (CIIS: cough, nasal discharge, dyspnea, depression and anorexia) and a faster normalization of body temperature . A slow decrease in white blood cell (WBC) count, the number of neutrophils, MID (mixed number of monocytes, eosinophils and basophils) and in the individual number of monocytes (CD14/CD45 positive cells) was observed in Groups I and III . In the blood of the calves which received oxytetracycline and flumethasone (Group II), leukocytosis, neutrophilia and monocytosis with concomitant lymphopenia and a low number of T cells (CD2+) was observed . Moreover, the calves treated with flumethasone exhibited a decrease in gamma-globulin concentration, and phagocytic parameters . Both drugs, flumethasone and meloxicam slightly decreased tumor necrosis factor (TNF) but meloxicam slightly increased the levels of interferon (IFN) in sera and in bronchoalveolar lavages (BALs) . These results suggest that the combination of meloxicam with an antibiotic in calves suffering from enzootic bronchopneumonia is superior to the antibiotic alone and also to the combination of the antibiotic with flumethasone. J Bone Joint Surg Br, 2003 Sep, 85(7), 956 - 9 Infection after total hip arthroplasty . The Avon experience; Blom AW et al.; Our aim in this study was to determine the outcome of hip arthroplasty with regard to infection at our unit . Infection after total joint arthroplasty is a devastating complication . The MRC study in 1984 recommended using vertical laminar flow and prophylactic antibiotics to reduce infection rates . These measures are now routinely used . Between 1993 and 1996, 1727 primary total hip arthroplasties and 305 revision hip arthroplasties were performed and 1567 of the primary and 284 of the revision arthroplasties were reviewed between five and eight years after surgery by means of a postal questionnaire, telephone interview or examination of the medical records of those who had died . Seventeen (1.08%) of the patients who underwent primary and six (2.1%) of those who underwent revision arthroplasty had a post-operative infection . Only 0.45% of patients who underwent primary arthroplasty required revision for infection . To our knowledge this is the largest multi-surgeon audit of infection after total hip replacement in the UK . The follow-up of between five and eight years is longer than that of most comparable studies . Our study has shown that a large cohort of surgeons of varying seniority can achieve infection rates of 1% and revision rates for infection of less than 0.5%. Br J Surg, 2003 Oct, 90(10), 1215 - 9 Significance of intraoperative peritoneal culture of fungus in perforated peptic ulcer; Shan YS et al.; BACKGROUND: The incidence of postoperative fungal infection is increasing and the gastrointestinal tract is the major source, but antifungal therapy in perforated peptic ulcer (PPU) is still controversial . The aim of this study was to determine the significance of intraoperative peritoneal fluid culture of fungus and establish the indications for treatment . METHODS: Between July 1997 and September 2001, all patients admitted with a PPU were studied . Clinical data and peritoneal fluid for culture were collected . Risk factors for a positive peritoneal fluid culture of fungus and outcome were evaluated, and related to the development of surgical site infection, duration of hospital stay and mortality rate . RESULTS: One hundred and forty-five patients with a PPU were included; 63 (43.4 per cent) had positive peritoneal fluid fungal culture . Age, preoperative organ failure, delay in operation, high Mannheim Peritonitis Index (MPI) and Acute Physiology And Chronic Health Evaluation (APACHE) II scores, and preoperative antibiotic therapy were risk factors for a positive fungal culture . Sex and an MPI score of 20 or more remained significant in multivariate analysis (P < 0.001) . Patients with a positive fungal culture had a higher incidence of surgical site infection, a longer hospital stay and a significantly higher mortality rate, especially when this was combined with a high MPI score . CONCLUSION: Positive peritoneal fungal culture was common and was a significant risk factor for adverse outcome in patients with a PPU . A high MPI score could be used as an indicator for prophylactic antifungal therapy . J Biol Chem, 2003 Nov 28, 278(48), 47862 - 7 Epub 2003 Sep 26. Protonation states of methionine aminopeptidase and their relevance for inhibitor binding and catalytic activity; Klein CD et al.; We have performed a computational study of different protomeric states of the methionine aminopeptidase active site using a combined quantum-mechanical/molecular mechanical simulation approach . The aim of this study was to clarify the native protonation state of the enzyme, which is needed for the development of novel irreversible inhibitors that can possibly be used as antiangiogenic and antibiotic drugs by virtual screening and other drug design methods . The results of the simulations indicated that two protonation states are possible without disturbing the overall geometry of the active site . We then verified experimentally the presence of the two protonation states by studying the substrate hydrolysis and inhibitor binding reactions at different pH values and come to the conclusion that one of the protomeric states is relevant for inhibitor binding, whereas the other is relevant for substrate hydrolysis . This result has implications for the development of other inhibitors of this class of enzymes and adds a new perspective to the pharmacological properties of the antiangiogenic drug fumagillin, which is an irreversible inhibitor of the human methionine aminopeptidase type II. South Med J, 2003 Sep, 96(9), 868 - 70 Experience with necrotizing fasciitis at a burn care center; Redman DP et al.; Necrotizing fasciitis is a soft tissue infection that causes necrosis of subcutaneous tissue and fascia but usually spares skin and muscle . Management of this condition consists of early diagnosis, broad-spectrum antibiotic coverage, aggressive surgical debridement, wound closure, and intensive supportive care . Mortality estimates reported in the literature have ranged from 20 to 75% . We report the cases of 12 patients treated at the Joseph M . Still Burn Center in Augusta, GA . Because aggressive surgical debridement combined with medical support is required for successful treatment, we recommend that treatment be administered at a burn care center . We performed a retrospective chart review of all patients admitted to our center with a diagnosis of necrotizing fascitis between May 1, 1995, and June 1, 2000 . Patients were managed collaboratively by burn surgeons and critical care intensivists in consultation with other appropriate specialists . The mean time from initial diagnosis until transfer to the burn center was 14 days (range, 0-60 d) . Complications included pneumonia, heart failure, metabolic abnormalities, anemia, and sepsis . Four (33%) of the 12 patients died, with the primary cause of death being multiorgan failure . Although our sample size is too small to reach statistical significance, the data suggest that early referral to a burn or wound care center improves patient outcome. J Infect Dis, 2003 Oct 1, 188(7), 1017 - 23 Epub 2003 Sep 26. Association between a specific Pneumocystis jiroveci dihydropteroate synthase mutation and failure of pyrimethamine/sulfadoxine prophylaxis in human immunodeficiency virus-positive and -negative patients; Nahimana A et al.; To investigate the possible association between different prophylactic sulfa drugs and the genotype of the Pneumocystis jiroveci dihydropteroate synthase (DHPS) gene, we examined DHPS polymorphisms in clinical specimens from 158 immunosuppressed patients (38 HIV-negative and 120 HIV-positive), using polymerase chain reaction-single-strand conformation polymorphism . Fifty-seven (36.1%) of 158 patients were infected with a mutant DHPS genotype . All patients who developed P . jiroveci pneumonia (PcP) while receiving pyrimethamine/sulfadoxine (PM/SD) prophylaxis (n=14) had a strain harboring DHPS with an amino acid change at position 57 (Pro-->Ser) . This mutation was only present in 20 (14%) of 144 patients not receiving prophylaxis (P<.001) . Hospitalization in a specific hospital was an independent risk factor for having P . jiroveci harboring the same DHPS mutation, which indirectly supports that interhuman transmission may affect the dissemination of the mutant strains. J Interferon Cytokine Res, 2003 Jul, 23(7), 379 - 93 Human alloreactive CTL interactions with gliomas and with those having upregulated HLA expression from exogenous IFN-gamma or IFN-gamma gene modification; Read SB et al.; By flow cytometry, a panel of 18 primary glioma cell explants exhibited high expression of class I HLA-A, B, C, but class II HLA-DR expression was absent . Freshly isolated normal brain cells displayed little or no HLA antigens . Alloreactive cytotoxic T lymphocytes (aCTL), sensitized to the HLA of the patient, were generated in a one-way mixed lymphocyte response (MLR) . The specificity of aCTL was confirmed to be to target cells (patient glioma cells or lymphoblasts) expressing the relevant HLA antigens . However, nontumor patient-specific aCTL did not lyse normal brain cells . Titration of antibodies to HLA class I into cytotoxicity assays blocked lysis of gliomas by aCTL, confirming aCTL T cell receptor (TCR) interactions with the class I antigen on gliomas . Furthermore, aCTL interactions with glioma cells caused their apoptosis . Coincubations of aCTL with gliomas resulted in upregulated cytokine secretion . Importantly, dexamethasone, an immunosuppressive steroid used for brain edema, did not affect aCTL lytic function against tumor, indicating that steroid-dependent patients may benefit from the immunotherapy . We also explored the use of interferon-gamma (IFN-gamma) to increase aCTL tumor recognition . Coincubation of gliomas with exogenous IFN-gamma (500 U/ml, 48 h) caused a 3-fold upregulation of HLA class I and a slight induction of class II antigen expression . Gene-modified glioma cells producing IFN-gamma similarly displayed upregulated HLA expression . Glioma cells incubated with exogenous IFN-gamma or IFN-gamma-transduced glioma cells were more susceptible to lysis by aCTL than their parental counterparts, thus supporting the concept of combining IFN-gamma cytokine gene therapy with adoptive aCTL immunotherapy for brain tumor treatment. BJU Int, 2003 Oct, 92(6), 589 - 91 The catheterized patient undergoing transurethral resection of the prostate: a survey of the current practice of British urologists; Wilson JR et al.; OBJECTIVE: To determine, using a postal questionnaire survey of practising British consultant urologists, the duration and type of antibiotic deemed most effective in patients with an existing indwelling catheter before transurethral resection of the prostate (TURP), as the value of prophylactic antibiotics before TURP is well recognized, but no data are available . METHODS: A questionnaire was posted to each of the 321 practising consultant urologists listed in the handbook of the British Association of Urological Surgeons (1998) . A hypothetical situation in the opening statement proposed 'a patient with an indwelling catheter is to undergo TURP' . The type, timing and duration of prophylactic antibiotic usage were elicited by circling the appropriate response from a choice of several possibilities . RESULTS: In all, 250 questionnaires were returned; 98% of respondents recognized the importance of the prophylactic use of antibiotics in catheterized patients undergoing TURP, and routinely use them . Most urologists (53%) use more than one dose, with most of these preferring a second dose on catheter removal (60%) . CONCLUSION: The magnitude and diversity of response suggests uncertainty about the appropriate prophylaxis in such patients, and the need for further studies to clarify this situation. Nucleic Acids Res Suppl, 2003, (3), 235 - 6 Various effects of paromomycin on tmRNA-mediated trans-translation; Konno T et al.; Trans-translation is an unusual translation in which tmRNA plays a dual function as a tRNA and an mRNA to relieve the stalled translation on the ribosome . In this study, we examined the effects of an aminoglycoside antibiotic, paromomycin, on several tmRNA-related events in vitro . A chemical footprinting study revealed that paromomycins bind tmRNA in the tRNA domain and in the middle of the long helix between tRNA and mRNA domains . Paromomycin bound in the tRNA domain inhibited aminoacylation, and the inhibition was suppressed by the addition of SmpB, a tmRNA binding protein . It was also found that paromomycin causes a shift of the translation-resuming point on tmRNA by -1 . The effect on initiation-shift was canceled by a mutation at the paromomycin binding site in 16S rRNA, but not by mutations in tmRNA . The effect of paromomycin on trans-translation differs substantially from that on canonical translation, in which it induces miscoding by modulating the A site of the decoding helix of the small subunit RNA of the ribosome. Am Surg, 2003 Sep, 69(9), 749 - 55; discusiion 755-6 The predictive value of preliminary bacterial colony counts from bronchoalveolar lavage in critically ill trauma patients; Mueller EW et al.; A common strategy for the diagnosis of ventilator-associated pneumonia (VAP) includes quantitative cultures from bronchoalveolar lavage (BAL) . Often, empiric antibiotic therapy is initiated and continued until the final culture report . However, approximately 60 per cent of BAL cultures rule out VAP . Preliminary BAL results, obtained earlier, may identify these patients and allow early discontinuation of empiric antibiotics . This is desirable because unnecessary antibiotic therapy results in increased bacterial resistance, adverse drug events, and increased costs . The purpose of this study was to determine the value of preliminary BAL results for predicting final BAL results . A total of 1579 isolates from 868 BAL cultures over a 3-year period were analyzed . Preliminary and final colony counts for each isolate were categorized as either no growth (NG), insignificant (1-99,999 cfu/mL), or significant (> or = 100,000 cfu/mL) . Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of preliminary results were calculated based on individual isolates and individual BAL samples . The presence of concurrent antibiotic therapy was collected for all false-negative isolates . On preliminary report, there were 367 isolates with NG, 820 isolates with insignificant growth, and 392 isolates with significant growth . Overall preliminary culture results had a sensitivity of approximately 90 per cent and specificity of >90 per cent for the presence of VAP . Preliminary culture results accurately predicted the presence or absence of VAP in 838 (96.5%) of the BALs performed . Individual isolates and BAL samples with insignificant preliminary growth had greater reliability in predicting the absence of VAP than those with NG . There was no difference in the number of false-negative isolates that were taken while concurrent antibiotic therapy was present between insignificant and NG groups . Preliminary culture results yielding either insignificant or significant growth are highly predictive for final colony counts of similar magnitude . BALs with preliminary results demonstrating no growth are not as reliable . Isolates with significant preliminary growth should be considered clinically important, and antibiotic therapy should be changed, if necessary, to target such organisms . Isolates with insignificant preliminary growth have a low rate of false negatives; therefore, empiric antibiotic therapy specific for such organisms could be discontinued before obtaining final results . Empiric antibiotics should be continued until the final results are available in those patients with NG BALs. Rays, 2003 Apr-Jun, 28(2), 183 - 90 Diagnostic imaging of the chest: exemplification of a reasoned integration; Canade A et al.; Based on the discussion and integrated management of a case of chest radiology, the reasoned approach to the perceptive-interpretative analysis and the "reasoned" diagnostic integration is tentatively exemplified . The request of a chest X-ray from the emergency department concerned a 75-year old patient, heavy smoker and chronic alcoholic with reduced vesicular murmur, diffuse hissing sounds, basal rales, weight loss and lack of appetite . The finding of right apical nodular opacities was critically evaluated to establish its diagnostic relevance (contours, opacity, site, accessory signs) . After broad-spectrum antibiotic therapy a second chest X-ray was substantially unchanged . For careful diagnostic assessment CT of the chest was performed and the definitive diagnosis of main airway obstruction, bronchiolitis and right nonspecific apical outcomes was established. Isr Med Assoc J, 2003 Sep, 5(9), 629 - 32 Vaginitis in a gynecologic practice in Israel: causes and risk factors; Dan M et al.; BACKGROUND: Vaginal symptoms are a leading reason for a patient to visit her gynecologist . Little is known about the prevalence of the different causes of vaginitis and the risk factors for this entity in Israel . OBJECTIVE: To determine the prevalence of the main forms of vaginitis: vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis, in a gynecologic practice in Israel . METHODS: We evaluated 208 patients presenting with vaginal symptoms to a gynecologic clinic; 100 asymptomatic women who attended the clinic for routine check-up served as controls . Demographic, medical and gynecologic histories were obtained, and a pelvic examination was performed in all patients . Vaginal specimens were tested for pH and amine reaction, smeared for Gram-staining and cultured for yeasts and Trichomonas vaginalis . Bacterial vaginitis was diagnosed using the Nugent scoring system . Candida infection was diagnosed by microscopic examination and by culture . RESULTS: Candida spp . was the most common pathogen, documented by microscopy and culture in 35.5% of symptomatic women and 15% of asymptomatic controls (P < 0.001) . Detection by culture only (negative microscopy) was documented in 18.7% of symptomatic patients and 15% of controls (P = 0.5) . Bacterial vaginosis (Nugent score > or = 7) was diagnosed in 23.5% of patients and 13% of controls (P = 0.04) . Trichomoniasis was present in 8.1% of symptomatic women and 4% of controls (P = 0.1) . The main risk factors were antibiotic use for candidiasis and lack of use of oral contraception and condom use for trichomoniasis . CONCLUSION: Candida was by far the most common pathogen detected in our population . A statistically significant difference between patients and controls was noted for the prevalence of microscopically diagnosed candidiasis and bacterial vaginosis. Psychiatr Prax, 2003 May, 30 Suppl 2, S226 - 8 {Circannual rhythm of drug use by a psychiatric clinic}; Koch HJ et al.; The total number per month of prescribed antibiotics or psychiatric drugs during one year (1998) was assessed by means of sine wave models {Y(t) = M + A x sin(2 x pi x t/tau + phi)} . M (no . of prescriptions per month) denotes mean frequency over one period, A (no . per month) denotes amplitude, tau (month) corresponds to the period and phi (month) to the phase of the fitted curve . Data were evaluated descriptively and chronograms including 95%-confidence limits were given . Significant nonlinear regression models could be calculated for amoxicillin, paroxetine, citalopram, amitriptyline and buspirone prescription behaviour . Both circannual and ultra-annual (period shorter than one year) rhythms of prescription were found . Peak values for antibiotic drug prescription during fall and winter is probably associated with higher incidence of infectious diseases . Antidepressant drug prescription has maxima in spring and fall, which is in keeping with the epidemiology of depressive disorders . The seasonality of buspirone prescription may reflect a basic periodicity of anxiety disorders . In conclusion, the chronopharmaco-epidemiological data of antibiotic and antidepressant drug prescription with circannual and ultra-annual rhythms may reflect the periodicity of infectious and psychiatric diseases. Curr Opin Investig Drugs, 2003 Aug, 4(8), 999 - 1003 MBI-226 . Micrologix/Fujisawa; Isaacson RE; Micrologix and Fujisawa are developing a gel formulation of MBI-226 for the potential treatment and prevention of various infections caused by both antibiotic-resistant and -sensitive bacteria . In September 2000, a phase III trial of MBI-226 for the potential prevention of catheter-related bloodstream infections was initiated. Semin Oncol, 2003 Aug, 30(4 Suppl 13), 3 - 9 Current management of chemotherapy-induced neutropenia: the role of colony-stimulating factors; Dale D; Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms . One important consequence, chemotherapy-induced neutropenia (CIN), places patients at risk of developing fever and life-threatening infections . These complications have substantial economic impact and may severely affect the quality of life of patients undergoing treatment of cancer . Currently, CIN is managed by delaying and reducing chemotherapy treatment with hematopoietic growth factors and with intravenous antibiotic therapy . Reducing chemotherapy may compromise treatment outcomes in potentially curable malignancies, such as early stage breast cancer and non-Hodgkin's lymphoma . Randomized clinical trials have clearly shown that granulocyte colony-stimulating factor (filgrastim) and the longer-acting pegylated granulocyte colony-stimulating factor pegfilgrastim, when administered 24 hours after chemotherapy before the occurrence of CIN, are effective in reducing the incidence and severity of neutropenia and its complications, including administration of full doses of chemotherapy without treatment delay . Dose-dense chemotherapy, ie, the administration of standard-dose chemotherapy in shorter cycles (made feasible with growth factor support), has recently been shown to improve outcomes in early stage breast cancer and non-Hodgkin's lymphoma . This review summarizes the clinical consequences of CIN and describes current best practices for the management of patients at risk for CIN. Am J Pathol, 2003 Oct, 163(4), 1557 - 66 A nonantibiotic chemically modified tetracycline (CMT-3) inhibits intimal thickening; Islam MM et al.; Recent research has shown that the tetracycline antibiotics are pluripotent drugs that inhibit the activity of matrix metalloproteinases (MMPs) and affect many cellular functions including proliferation, migration, and matrix remodeling . We have shown that doxycycline inhibits MMP activity and intimal thickening after injury of the rat carotid artery, however we do not know whether these effects are because of the antibiotic, anti-MMP, or other actions of doxycycline . Recently, chemically modified tetracyclines have been synthesized that lack antibiotic activity but retain anti-MMP activity (CMT-3), or lack both antibiotic and anti-MMP activity (CMT-5) . In the current study we have assessed the effects of treatment with CMT-3 or CMT-5 on intimal thickening after balloon catheter injury of the rat carotid artery . Rats were treated by oral gavage with 15 mg/kg/day CMT-3 or CMT-5 . CMT-3 significantly reduced smooth muscle cell (SMC) proliferation in both the medial and intimal layers of the injured rat carotid artery compared to CMT-5 . Furthermore, CMT-3 inhibited SMC migration from the media to the intima by 86% at 4 days after injury . CMT-3 also decreased MMP-2 activity . Finally, we found that CMT-3 treatment resulted in a significant reduction in intimal cross-sectional area from 0.23 +/- 0.01 mm(2) in the CMT-5 control group to 0.19 +/- 0.01 mm(2) . There was also a reduction in elastin and collagen accumulation within the intima . We conclude that CMT-3 attenuated intimal thickening after arterial injury by inhibiting SMC proliferation, migration and MMP activity, and accumulation of extracellular matrix . The inhibitory effects of CMT-3 were independent of the antibiotic properties, but were dependent on the anti-MMP activity of the tetracycline family. Best Pract Res Clin Gastroenterol, 2003 Oct, 17(5), 785 - 91 Probiotics and Helicobacter pylori; Felley C et al.; There is substantial evidence that probiotics modulate Helicobacter pylori colonization of the gastric mucosa . This chapter presents the data currently available to support an interaction between probiotics and H . pylori, the importance of lactic acid production by probiotics and their capacity to release bacteriocins or secrete antibiotics . The ability of probiotics to interfere with H . pylori adhesion to epithelial cells and their capacity to attenuate H . pylori-induced gastritis in man is addressed . Finally, the potential of probiotics to modify the H . pylori eradication rate and the antibiotic-associated gastrointestinal side-effects during H . pylori eradication therapy are reviewed. J Clin Anesth, 2003 Aug, 15(5), 378 - 81 Anesthetic implications of cervicofacial necrotizing fasciitis; Durrani MA et al.; Cervicofacial necrotizing fasciitis is a necrotizing soft tissue infection of face and neck spreading at the level of fascia . It has been described as a putrid ulcer, phagedaena, and hospital gangrene . It has a high mortality rate, and presents a challenge to anesthesiologists who must secure an airway to deliver anesthesia safely . We report a case of cervicofacial necrotizing fasciitis in which the patient underwent repeated radical surgical debridement of face and neck, including a mandibulectomy . These critically ill patients often present with sepsis and multiple system organ failure . Extensive preoperative evaluation, invasive monitoring, and possibly the use of vasopressors and inotropes are essential in treating these patients . The tracheas of these patients should remain intubated after initial debridement . Tracheostomy should be performed early . Antibiotic therapy, nutritional support, early debridement, and hyperbaric oxygen therapy all help to decrease mortality in these patients. Amyotroph Lateral Scler Other Motor Neuron Disord, 2003 Jun, 4(2), 81 - 9 In vitro reactive nitrating species toxicity in dissociated spinal motor neurons from NFL (-/-) and hNFL (+/+) transgenic mice; Strong M et al.; We utilized fetal spinal motor neurons isolated from either NFL (-/-) or hNFL (+/+) transgenic mice to determine whether the loss of the low molecular weight neurofilament protein (NFL) places spinal motor neurons at a greater risk for cell death triggered by reactive nitrating species (RNS) . After 21 days in serum-free, antibiotic-free medium, both the NFL (-/-) and hNFL (+/+) motor neurons developed neurofilamentous aggregates . Cultures were then exposed to nitric oxide(100 microM NOC 5, 100 microM NOC 12, or 2 mM sodium nitroprusside) or to peroxynitrite (250 mM SIN-1) forvarying intervals . NFL (-/-) cultures demonstrated extensive numbers of apoptotic neurons within six hours and complete cell loss by 24 hours in response to NOC 5 and NOC 12 . In contrast, apoptosis was only observed in the motor neurons derived from control (C57bl/6) or hNLF (+/+) mice at 24 hours . In response to 2 mM sodium nitroprusside, necrosis was induced in all cells within 60 minutes . In response to 250 mM SIN-1, both C57bl/6 and hNFL (+/+) cells survived to six hours with only minimal evidence of degeneration while NFL (-/-) motor neurons were necrotic by 60 minutes . These observations suggest that NFL deficient motor neurons are at an enhanced risk of cell death mediated by RNS. Eur Biophys J, 2004 Jul, 33(4), 285 - 90 Epub 2003 Sep 23. Perturbation of DPPC bilayers by high concentrations of pulmonary surfactant protein SP-B; Morrow MR et al.; Deuterium ((2)H) NMR has been used to observe perturbation of dipalmitoylphosphatidylcholine (DPPC) bilayers by the pulmonary surfactant protein B (SP-B) at concentrations up to 17% (w/w) . Previous (2)H NMR studies of DPPC/dipalmitoylphosphatidylglycerol (DPPG) (7:3) bilayers containing up to 11% (w/w) SP-B and DPPC bilayers containing up to 11% (w/w) synthetic SP-B indicated a slight effect on bilayer chain order and a more substantial effect on motions that contribute to decay of quadrupole echoes obtained from bilayers of deuterated DPPC . This is consistent with the perturbation of headgroup-deuterated DPPC reported here for bilayers containing 6 and 9% (w/w) SP-B . For the higher concentrations of SP-B investigated in the present work, (2)H NMR spectra of DPPC deuterated in both the headgroup and chain display a prominent narrow component consistent with fast, large amplitude reorientation of some labeled lipid . Similar spectral perturbations have been reported for bilayers in the presence of the antibiotic polypeptide nisin . The observation of large amplitude lipid reorientation at high SP-B concentration could indicate that SP-B can induce regions of high bilayer curvature and thus provides some insight into local interaction of SP-B with DPPC . Such local interactions may be relevant to the formation, in vitro and in vivo, of tubular myelin, a unique structure found in extracellular pulmonary surfactant, and to the delivery of surfactant material to films at the air-water interface. J Orthop Trauma, 2003 Sep, 17(8), 549 - 54 Correction of tibial malunion and nonunion with six-axis analysis deformity correction using the Taylor Spatial Frame; Feldman DS et al.; OBJECTIVE: To determine the effectiveness of six-axis analysis deformity correction using the Taylor Spatial Frame for the treatment of posttraumatic tibial malunions and nonunions . DESIGN: Retrospectively reviewed, consecutive series . Mean duration of follow-up was 3.2 years (range 2-4.2 years) . SETTING: Tertiary referral center for deformity correction . PATIENTS/PARTICIPANTS: Eighteen patients were included in the study (11 malunions and 7 nonunions) . All deformities were posttraumatic in nature . The mean number of operations before the application of the spatial frame was 2.6 (range 1-6 operations) . All patients completed the study . INTERVENTION: Six-axis analysis deformity correction using the Taylor Spatial Frame (Smith & Nephew, Memphis, TN) was used for correction of posttraumatic tibial malunion or nonunion . Nine patients had bone grafting at the time of frame application . One patient with a tibial plafond fracture simultaneously had deformity correction and an ankle fusion for a mobile atrophic nonunion . Two patients had infected tibial nonunions that were treated with multiple debridements, antibiotic beads, and bone grafting at the time of spatial frame application . A rotational gastrocnemius flap was used to cover a proximal third tibial defect in one patient . The average length of time the spatial frame was worn, time to healing, was 18.5 weeks (range 12-32 weeks) . MAIN OUTCOME MEASUREMENTS: Assessment of deformity correction in six axes, knee and ankle range of motion, incidence of infection, and return to preinjury activities . RESULTS: Of the 18 patients treated with the Taylor Spatial Frame, with adjunctive bone graft as necessary, 17 achieved union and significant correction of their deformities in six axes (ie, coronal angulation and translation, sagittal angulation and translation, rotation, and shortening) . Fifteen patients returned to their preinjury activities at last follow-up . CONCLUSION: Six-axis analysis deformity correction using the Taylor Spatial Frame is an effective technique to treat posttraumatic malunions and nonunions of the tibia, with several advantages over previously used devices. Aviat Space Environ Med, 2003 Sep, 74(9), 985 - 9 Optic neuropathy following an altitude exposure; Steigleman A et al.; This case report describes a 20-yr-old man who presented with retro-orbital pain and blurred vision in his left eye 3 wk after an altitude exposure in a hypobaric chamber . He was found to have significant deficits in color vision and visual fields consistent with an optic neuropathy in his left eye . The patient was diagnosed with decompression sickness and treated with hyperbaric oxygen with a U.S . Navy Treatment Table VI . All signs and symptoms resolved with a single hyperbaric oxygen treatment but recurred . A head MRI revealed a left frontoethmoid sinus opacity . A concomitant sinusitis was diagnosed . The patient had full resolution of symptoms after a total of four hyperbaric oxygen treatments and antibiotic therapy at 6-wk follow-up . Although a para-infectious etiology for this patient's optic neuropathy cannot be excluded, his history of altitude exposure and significant, rapid response to hyperbaric oxygen treatment strongly implies decompression sickness in this case. Crit Care Med, 2003 Sep, 31(9), 2385 - 90 Rates of infection for single-lumen versus multilumen central venous catheters: a meta-analysis; Dezfulian C et al.; OBJECTIVE: Since the introduction of multilumen central venous catheters two decades ago, there has been controversy whether the additional lumens place patients with these catheters at higher risk for infection . Our objective was to determine the risk of catheter-related bloodstream infection (CRBSI) and catheter colonization in multilumen catheters compared with single-lumen catheters . DATA SOURCE: Studies were identified by a computerized search of MEDLINE, EMBASE, CINAHL, Current Contents, and PREMEDLINE databases and by review of bibliographies and expert consultation . Studies comparing the prevalence of CRBSI or catheter colonization among single-, double-, and triple-lumen central venous catheters were included . We excluded studies if they included central venous catheters that were long-term, cuffed, tunneled, or coated with antibiotic or antiseptic agents . DATA ABSTRACTION: Two independent reviewers abstracted data on: 1) risk factors for CRBSI and colonization, 2) outcome definitions used, 3) the absolute prevalence of CRBSI and catheter colonization, and 4) study design and quality . DATA SYNTHESIS: A total of 15 studies met inclusion criteria . Summary odds ratios were calculated using a random-effects model . Although CRBSI was more common in multilumen catheters (summary odds ratios, 2.15; 95% confidence interval, 1.00-4.66), catheter colonization was not (summary odds ratios, 1.78; 95% confidence interval, 0.92-3.47) . Tests for heterogeneity, however, suggested substantial variation by study . When only studies of higher quality were included, multilumen catheters were found not to be associated with a significant increase in CRBSI prevalence (summary odds ratios, 1.30; 95% confidence interval, 0.50-3.41) . CONCLUSIONS: Multilumen central venous catheters may be associated with a slightly higher risk of infection when compared with single-lumen catheters; however, this relationship diminishes when only high-quality studies that control for patient differences are considered . The slight increase in infectious risk when using multilumen catheters is likely offset by their improved convenience, thereby justifying the continued use of multilumen vascular catheters. Spine, 2003 Sep 15, 28(18), E384 - 9 Acute pyogenic sacroiliitis without predisposing conditions; Doita M et al.; STUDY DESIGN: Clinical and imaging findings of patients diagnosed with pyogenic sacroiliitis were retrospectively analyzed . OBJECTIVES: To characterize the clinical and magnetic resonance features of patients with acute pyogenic sacroiliitis without the usually known predisposing conditions and to investigate the diagnostic value of magnetic resonance imaging in detecting the early stages of pyogenic sacroiliitis . SUMMARY OF BACKGROUND DATA: Pyogenic sacroiliitis is relatively uncommon, and accurate diagnosis is frequently delayed due to lack of awareness by clinicians and nonspecific clinical presentation . There have been few reports that have evaluated the clinical features of acute pyogenic sacroiliitis and investigated the diagnostic capabilities of magnetic resonance imaging in detecting pyogenic sacroiliitis in the early stages . METHODS: The clinical data of 9 patients (6 male, 3 female; average age 27.3 years) diagnosed with acute pyogenic infection of the sacroiliac joint were retrospectively analyzed . Magnetic resonance images as well as computed tomography of the sacroiliac joints were available in all cases . Seven of the patients underwent 99mtechnetium bone scans . RESULTS: All patients showed positive findings on magnetic resonance images, whereas 99mtechnetium bone scans were positive in six of seven patients . Eight patients responded well to treatment with intravenous antibiotic therapy, whereas one patient required debridement of the sacroiliac joint following conservative treatment . CONCLUSIONS: Both magnetic resonance imaging and technetium bone scanning are sensitive for localizing occult sites of bone inflammation . Magnetic resonance imaging may provide more useful information than bone scanning by screening for abnormalities in the sacroiliac joint region . With prompt appropriate antibiotic therapy, clinical improvement of patients can be expected. Am J Med Sci, 2003 Sep, 326(3), 152 - 5 Disseminated Actinomyces meyeri infection resembling lung cancer with brain metastases; Colmegna I et al.; Thoracic actinomycosis can resemble bronchogenic carcinoma in its clinical presentation and radiographic appearance . We report a case of pulmonary actinomycosis caused by Actinomyces meyeri in which hematogenous dissemination caused multiple brain abscesses resembling metastatic lung cancer . The correct diagnosis was made by thin-needle aspiration of a pleura-based lung mass . The pathogen isolated was further identified with the use of 16S rDNA sequencing . Antibiotic therapy resulted in rapid improvement of the lung lesion; however, the brain lesions required surgical drainage . Antibiotics were continued for more than a year before magnetic resonance images showed complete resolution of the cerebral abscesses. Enferm Intensiva, 2003 Jul-Sep, 14(3), 80 - 7 {Selective digestive decontamination}; Montial Fernandez E et al.; OBJECTIVES: The objectives of the study were: to explain our protocol of selective digestive decontamination (SDD); to know the therapeutic activity that the protocol implies in the nursing staff; to assess the impact on the incidence of ventilatorassociated pneumonia . METHODS DESIGN: Prospective descriptive study for time measurements, and non randomized comparative study for the incidence of ventilatorassociated pneumonia . We calculate time means and 95 percent confidence interval (CI) . We calculate ventilatorassociated pneumonia relative risk and number-needed-to-treat (NNT) . SETTING: Intensive care unit with 13 beds reference for neurocritical illness . STUDY PERIOD: Control group from November-2001 to April-2002 . Treatment group from May-2002 to November 2002 . PATIENTS: consecutive patients who were admitted in our intensive care department with mechanical ventilation for more than 48 hours.Results . A total of 122 consecutive patients were included: control group 62 patients, treatment group 60 patients . We have recorded 136 SDD administration time and 16 vigilance culture records . The SDD administration mean time was 8.11 minutes (95% CI, 7.59-8.63) . Morning Nursing Duty Schedule spent significantly more time mean 10.7 minutes (95% CI, 9.87- 11.89) than afternoon 8.1 (95% CI, 7.20-9.08) (p < 0.05) and night 6.9 (95% CI, 6.39-7.46) . There was a significant difference between time spent in SDD administration in trauma patients (p < 0.05) 7.45 (95% CI, 6.63-8.27) and medical patients 8.71 minutes (95% CI, 8.41-9.01) . We spent a mean of 9 minutes (CI 8-10) in culture sampling . In the treatment group the ventilator associated pneumonia incidence relative risk was 0.28 (CI 0.13-0.63) with a NNT of 4 (CI 3-8) . CONCLUSION: In our patients SDD administration represents the 2.5% of our therapeutic activity time per patient and reduces the ventilator associated pneumonia risk. Childs Nerv Syst, 2003 Nov, 19(10-11), 773 - 6 Epub 2003 Sep 10. A child with spinal intramedullary abscess; Guzel N et al.; CASE REPORT: We report a case of an intramedullary spinal cord abscess (ISCA) in a 14-month-old child . This case demonstrates clinical and radiological features and emphasizes the importance of early diagnosis and treatment . Early surgical intervention and adjuvant antibiotic therapy have been shown to improve the clinical outcome . Successful outcome depends on early diagnosis and aggressive management . DISCUSSION: Spinal intramedullary abscess is a rare neurosurgical entity . They can hardly be distinguished from neoplasms . Hart described the first case in 1830 . Since then, approximately 70 cases have been reported . An acute spinal intramedullary abscess may present as a cord syndrome with back pain and fever, contrasting with chronic spinal intramedullary abscess, which tends to have a less specific symptomatology. Cancer Chemother Pharmacol, 2003 Dec, 52(6), 449 - 52 Epub 2003 Sep 09. Mylotarg, fludarabine, cytarabine (ara-C), and cyclosporine (MFAC) regimen as post-remission therapy in acute myelogenous leukemia; Tsimberidou AM et al.; PURPOSE: Mylotarg, a humanized anti-CD33 antibody linked to an antitumor antibiotic, is approved for the treatment of patients with relapsed acute myeloid leukemia (AML) . Its role as a component of post-remission therapy in AML has not been established . The Mylotarg, fludarabine, cytarabine, and cyclosporine (MFAC) regimen was evaluated in patients in complete remission following Mylotarg-containing regimens . METHODS: The MFAC regimen comprised: Mylotarg 4.5 mg/m2 intravenously (i.v.) over 2 h after a loading dose of cyclosporine A (CSA) on day 1; fludarabine 15 mg/m2 i.v . over 30 min every 12 h for six doses on days 2 through 4; ara-C 0.5 g/m2 over 2 h every 12 h for six doses on days 2 through 4, 4 h after fludarabine started; CSA 6 mg/kg over 2 h, followed by 16 mg/kg continuous i.v . infusion on days 1 and 2 . Patients in complete remission (CR) commenced idarubicin and ara-C (IA) alternating with MFAC or vice versa for 9 months from the date of CR . Idarubicin was administered at 8 mg/m2 on days 1 and 2 and ara-C at 1.5 g/m2 on days 1 and 2 . RESULTS: A total of 22 patients received 76 courses of MFAC (35 courses) alternating with IA (41 courses) or vice versa . The interval between courses, and degrees of myelosuppression, were equivalent in the alternating regimens . Failure-free and 12-month survival rates of were 32% and 55%, respectively . Grade 3/4 toxicities, including sepsis, neutropenic fever, and nausea/vomiting, were equivalent with MFAC and IA . CONCLUSIONS: Post-remission therapy with MFAC is feasible and well tolerated in patients with AML. Mol Biotechnol, 2003 Sep, 25(1), 79 - 87 Modification of tumor cells with Fas (CD95) antigen gene and Fas ligand (CD95L) gene transfection by electroporation for immunotherapy of cancer; Shimizu M et al.; Electroporation is a method for introducing DNA into cells by using a high-voltage electric field . This method is very simple and easily manipulated . We describe here a method for the modification of tumor cells with the Fas/Apo-1 (CD95) antigen-gene and Fas ligand (FasL)-gene transfection through the use of electroporation, and suggest that the Fas-FasL system is a good target for the induction of apoptosis-mediated antitumor activity . The Fas receptor/ligand system induces apoptosis and plays an important role in regulation of the immune system . In the method described, hepatoma MH134 (Fas- and FasL-) is transfected with murine Fas and FasL cDNA . A single administration of monoclonal anti-Fas antibody efficiently suppresses the growth of F6b (MH134+Neo+Fas) tumors but not that of N1d (MH134+Neo) tumors in gld/gld lpr/lpr mice . MH134+Neo+FasL tumor cells were rejected after the induction of inflammation with infiltration of neutrophils in mice . These results suggest that electroporation and Fas-mediated apoptosis are a good method for inducing of antitumor activity. Farmaco, 2003 Sep, 58(9), 995 - 8 1,2-dithiolan-3-ones and derivatives structurally related to leinamycin . Synthesis and biological evaluation; Salvetti R et al.; Leinamycin, an antitumor antibiotic isolated from Streptomyces sp., shows a 1,2-dithiolan-3-one 1-oxide heterocycle that appears to be involved in the biological activity . Several derivatives related to 1,2-dithiolan-3-one 1-oxide have been prepared and their activity as antineoplastic agents have been investigated . The synthesized compounds did not display a significative antitumor or cytotoxic activity in vitro. Farmaco, 2003 Sep, 58(9), 683 - 90 Synthesis and biological evaluation of new amino acids structurally related to the antitumor agent acivicin; Conti P et al.; A set of racemic conformationally constrained analogues of the antitumor antibiotic acivicin (+)-1 has been prepared through a strategy based on 1,3-dipolar cycloaddition of bromonitrile oxide to suitable dipolarophiles . The bromo analogue (2) of acivicin was also synthesized and tested as a reference compound, together with its stereoisomer 3 . The antitumor properties of novel amino acids 4-7 were evaluated in vitro against human tumor cell lines . Their efficacy to inhibit glutamate synthase (GltS) from Azospirillum brasilense was also assayed . None of the studied compounds, but 2, showed significant activity. Int J Antimicrob Agents, 2003 Sep, 22(3), 274 - 8 Mycobacterial efflux pumps and chemotherapeutic implications; Viveiros M et al.; The demonstration of the existence of active efflux pumps in mycobacteria raises the question of whether or not these can increase in number and activity rendering wild-type mycobacteria increasingly resistant to a given antibiotic . This could be a mechanism by which mutated resistant strains become better fit to the selective environment . Mycobacterium tuberculosis genome analysis reveals several genes encoding putative drug efflux pumps . During the course of tuberculosis chemotherapy many of these pumps might play a role in the survival of the mycobacterial populations . Compounds capable of inactivating these pumps could improve anti-tuberculous therapeutics. Curr Infect Dis Rep, 2003 Oct, 5(5), 391 - 397 Infections in Diabetic Foot Ulcerations; Joseph WS et al.; Diabetic foot complications are the largest nontraumatic cause of lower extremity amputations, accounting for almost 90,000 amputations per year . Most of these amputations are the result of infections caused by ulcerations of the foot that are not recognized or treated in an appropriate and timely fashion . Often, cultures are taken when not warranted and antibiotics are administered when no infection is present, causing significant increases in resistant organisms . Although there have been many attempts to classify diabetic foot lesions, none of these systems are specific for infectious complications . This paper presents a system for identifying the presence and severity of infection with suggestions for appropriate empiric antibiotic therapy. Pediatr Dent, 2003 Jul-Aug, 25(4), 383 - 8 Oral manifestations of cyclic neutropenia in a Japanese child: case report with a 5-year follow-up; Nakai Y et al.; Cyclic neutropenia is an uncommon hematologic disorder characterized by a marked decrease in the number of neutrophils in the peripheral blood occurring at regular intervals . The neutropenic phase is characteristically associated with clinical symptoms such as recurrent fever, malaise, headaches, anorexia, pharyngitis, ulcers of the oral mucous membrane, and gingival inflammation . This case report describes a Japanese girl who has this disease and suffers from periodontitis and oral ulceration . Her case has been followed up for the past 5 years from age 7 to 12 . The importance of regular oral hygiene, careful removal of subgingival plaque and calculus, and periodic and thorough professional mechanical tooth cleaning was emphasized to arrest the progress of periodontal breakdown . Local antibiotic application with minocycline ointment in periodontal pockets was beneficial as an ancillary treatment, especially during neutropenic periods. Psychiatr Prax, 2003 May, 30(Suppl 2), 226 - 228 {Circannual Periodicity of Prescriptions in a Psychiatric Hospital}; Koch HJ et al.; The total number per month of prescribed antibiotics or psychiatric drugs during one year (1998) was assessed by means of sine wave models {Y(t) = M + A x sin(2 x pi x t/tau + Phi)} . M (no . of prescriptions per month) denotes mean frequency over one period, A (no . per month) denotes amplitude, tau (month) corresponds to the period and Phi (month) to the phase of the fitted curve . Data were evaluated descriptively and chronograms including 95 %-confidence limits were given . Significant nonlinear regression models could be calculated for amoxicillin, paroxetine, citalopram, amitriptyline and buspirone prescription behaviour . Both circannual and ultra-annual (period shorter than one year) rhythms of prescription were found . Peak values for antibiotic drug prescription during fall and winter is probably associated with higher incidence of infectious diseases . Antidepressant drug prescription has maxima in spring and fall, which is in keeping with the epidemiology of depressive disorders . The seasonality of buspirone prescription may reflect a basic periodicity of anxiety disorders . In conclusion, the chronopharmaco-epidemiological data of antibiotic and antidepressant drug prescription with circannual and ultra-annual rhythms may reflect the periodicity of infectious and psychiatric diseases. Ann Otolaryngol Chir Cervicofac, 2003 Sep, 120(4), 207 - 15 {Infectious complications after surgery for hypopharyngeal and laryngeal carcinomas}; Manceau A et al.; OBJECTIVE: The objective of this study was to analyze the infectious complications of procedures for carcinoma of the hypopharynx and the larynx to optimize the prevention of septic risks . MATERIAL AND METHODS: This retrospective study included 608 patients who underwent total (n=270) or partial (n=338) laryngectomy between 1984 and 1999 . The procedures were performed under rigorous conditions of surgical asepsis and with prolonged antibiotic chemotherapy depending on the type of laryngectomy and past history of external radiotherapy . Twenty factors were studied . Univariate analysis, including 9 factors, and multivariate analysis were performed . RESULTS: The global rate of infectious complications was 11.1% . The percentages of salivary leaks, other wound infections and non-wound infections were respectively 11.9%; 1.5%; 1.5% for total laryngectomy and 1.8%; 2.4%; 3.8% for partial laryngectomy . Statistically significant factors were tumor stage, postoperative hematoma, postoperative lymphorrhea and, to a lesser degree, pharyngeal localization . CONCLUSION: Our rate of infectious complications in oncologic pharyngeal and laryngeal surgery, which is low compared with data in the literature, emphasizes the importance of strict measures of surgical asepsis and prolonged antibiotic chemotherapy as is recommended for so-called contaminated surgery. Di Yi Jun Yi Da Xue Xue Bao, 2003 Sep, 23(9), 981 - 3 {Endoscopic nasobiliary drainage for acute obstructive suppurative cholangitis with multiple organ failure: report of 25 cases}; Song H et al.; OBJECTIVE: To explore the treatment of acute obstructive suppurative cholangitis (AOSC) with multiple organ failure (MOF) . METHODS: Twenty-five patients with AOSC complicated by MOF underwent non-surgical comprehensive therapies, including endoscopic naso biliary drainage (ENBD), flushing and antibiotic perfusion through the naso biliary catheter . The alterations of the levels of serum total bilirubin and common bile duct diameter were measured both preoperatively and postoperatively, with retrospective analysis of the patients' clinical record . RESULTS: Of all the 25 patients, 23 underwent endoscopic retrograde cholangiopancreatography (ERCP) with successful placement of the nasobiliary catheters and bile drainage, and MOF was corrected . The cure rate of the this group of patients was 92.0%, with two cases being transferred for emergency surgical treatment . CONCLUSION: Comprehensive treatment consisting of ENBD, flushing and antibiotic perfusion through the naso biliary catheter and intravenous use of antibiotics is effective and safe for the treatment of AOSC complicated by MOF. Am J Ther, 2003 Sep-Oct, 10(5), 377 - 9 Diagnosis and treatment of multiple sclerosis and amyotrophic lateral sclerosis: neuropathies from Bordetella pertussis; Fiore D; Having found positive the research for anti-Bordetella antibodies in the 95.47% of 92 patients affected by defined multiple sclerosis and in the 100% of 55 patients affected by non-patched neuropathies (amyotrophic lateral sclerosis and correlated neuropathies), I reassessed the pathogenesis of the neuropathies from Bordetella pertussis . In the two categories of neuropathies (with and without patches), the beginning pathogenetic mechanisms are the same: 1) pertussis re-infection in patients with mucociliary barrier defect; 2) pertussis toxins passage in the blood; and 3) formation of circulating immune complexes . In multiple sclerosis, astrocytes produce class II human leukocyte antigens, the endothelia of the small brain vessels show the "adhesion molecules," and the immune complexes fall in the central nervous system (patches are formed) . In amyotrophic lateral sclerosis and in the other non-patched neuropathies, the astrocytes do not produce the class II human leukocyte antigens, the endothelia do not show adhesion molecules, and immune complexes do not fall in the central nervous system; but they increase in blood until they inhibit the ulterior antibodies production . For relative antibodies lack, pertussis toxins fix directly on neuro-epithelia; their pathogenic power and physiopathologic astrocytes role in the central nervous system produce the damage . With a blood sample, we can assess Bordetella etiology . In all these neuropathies, an extended antibiotic therapy to clear mucosae and to prevent reinfections is necessary. Am J Ther, 2003 Sep-Oct, 10(5), 324 - 9 An open-label, single-center, phase IV clinical study of the effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) in reducing the duration and symptoms of the common cold in school-aged subjects; McElroy BH et al.; Each year, more than 62 million cases of the common cold in the United States require medical attention and more than 80% affect school-aged children . The objective of this prospective, intent-to-treat, phase IV study was to determine the therapeutic and prophylactic effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) for the common cold . Zinc lozenges were administered once daily during the cold season for prophylaxis . For therapeutic purposes, lozenges were given 4 times per day . The primary objective of the study was the treatment effect on cold duration, and the secondary objective was the effect on the number of common colds . A putative control from our previous study was used for comparison . A total of 178 children, ages 12 to 18 years, was enrolled, of which 134 met criteria for efficacy analysis . The average cold duration with therapeutic lozenge use was 6.9 +/- 3.1 days, significantly shorter than the 9.0 +/- 3.5 days found in the control group (P < 0.001) . The mean number of colds was 1.28 +/- 1.03 with zinc lozenge prophylaxis versus 1.7 +/- 1.91 without prophylaxis (P < 0.05), a 25% reduction . With prophylaxis, 25% of the subjects did not experience a cold and two-thirds never had a cold or only had 1 cold . There was no antibiotic use for any cold, and there were no adverse events reported . Results of this study are consistent with those from our previous retrospective study showing significantly shorter cold duration and fewer colds with the use of zinc gluconate glycine lozenges . The zinc gluconate glycine lozenges are well tolerated and are an easy-to-administer therapy that has the potential to substantially reduce cold-related school absences and antibiotic use and misuse as well as to provide a cost saving. Clin Exp Immunol, 2003 Oct, 134(1), 86 - 91 cDNA cloning, expression and characterization of an allergenic L3 ribosomal protein of Aspergillus fumigatus; Saxena S et al.; Aspergillus fumigatus (Afu) is an important fungal pathogen causing allergic and invasive respiratory disorders . A plethora of multi-functional allergens/antigens secreted by Afu have been implicated in pathogenesis . The present study was undertaken to identify and characterize novel Afu allergen/antigen by cDNA library approach . cDNA library of Afu was immunoscreened with pooled sera of allergic bronchopulmonary aspergillosis (ABPA) patients . The cDNA clone, TS1, reacting significantly with specific IgG antibodies, was selected . cDNA was subcloned and expressed in Escherichia coli . Sequencing of the cDNA revealed an open reading frame (ORF) of 1179 bases coding for a protein with an approximate molecular weight of 44 kDa . Immunoreactivity of the recombinant TS1 protein (rTS1) was evaluated by ELISA and Western blot analysis using pooled sera of ABPA patients . The rTS1 exhibited binding to specific IgG and IgE antibodies present in sera of ABPA patients . The deduced amino acid sequence showed homology to 60S ribosomal protein L3 (RpL3) of Aspergillus nidulans, Saccharomyces cerevisiae and Homo sapiens . The RpL3 of S . cerevesiae, tcm1, to which TS1 sequence shows significant homology (72% identity), is known to be responsible for conferring resistance against trichodermin (antibiotic, inhibiting protein synthesis) . The present study has led to identification, cloning and expression of a 44-kDa novel allergen/antigen of Afu with sequence homology to L3 ribosomal protein with a probable role in resistance of Afu to antifungal drugs . Sixty-four per cent sequence identity of Afu RpL3 with human RpL3 and common regions in their predicted epitopes suggest a possibility of involvement of Afu RpL3 in autoimmune reactions due to molecular mimicry. Saudi Med J, 2003 Sep, 24(9), 1010 - 2 The clinical utility of intrapleural streptokinase in a patient with bilateral pleural empyema; Al-Ahmadi NA et al.; Bilateral thoracic empyema is a rare clinical entity particularly when presented as an initial clinical manifestation . Antibiotic therapy with intercostal thoracostomy drainage tube of the infected pleural space in complicated parapneumonic empyema may not be adequate in many conditions due to multiloculation and adhesion . We describe in this case a previously healthy middle aged male, presented with a bilateral thoracic empyema that was treated initially with antibiotics and intercostal drainage tube without optimal drainage results . The administration of twice daily intrapleural streptokinase prolonged for the duration of more than 10 days proved to be safe and effective as an alternative line of management in such a clinical condition. Rev Esp Quimioter, 2003 Jun, 16(2), 221 - 6 {Use of levofloxacin in the hospital}; Castells X et al.; Levofloxacin is a new, recently commercialized fluoroquinolone . We aimed to assess the use of levofloxacin after its inclusion in the hospital drug guide . In a prospective observational study, patients treated with levofloxacin in a university hospital were selected from July 2000 to June 2001 . Using a structured questionnaire, data were recorded on patients' demographic characteristics and comorbidities, indications for levofloxacin use and previous use of other antibiotics . In addition, the adherence to the instructions for use as recommended by the antibiotic subcommittee of the hospital, and the use of other alternative antibiotics were analyzed . Ninety-seven patients were treated {mean age 67 years; range 17-93; 64 men}, of whom 83 (85.6%) had comorbidity and 51 (52.6%) a possible allergy to the betalactam antibiotics . The treatment began after the use of other antibiotics in 47 (48.5%) patients . The main clinical indications were pneumonia (54; 55.7%) and acute exacerbation of chronic bronchitis (25; 25.8%) . The use of other antibiotics was possible in 56 (57.7%) patients, and levofloxacin was only used according to the recommended indications in 41 (42.3%) . Levofloxacin is mainly used in the treatment of patients with respiratory infections, those who are allergic to the betalactam antibiotics and those previously treated with other antibiotics; however, in many cases, the use of other antibiotics may still be possible . As part of the antibiotic policy, it is necessary to define the indications of use for new antibiotics introduced in the hospital and surveillance studies need to be developed. Rev Esp Quimioter, 2003 Jun, 16(2), 188 - 94 {Streptomycin as second-line chemotherapy for tuberculosis}; Ruiz P et al.; Streptomycin was the first antibiotic to be used against Mycobacterium tuberculosis . It was used for years in monotherapy regimens, thereby resulting in the appearance of resistance and the relegation of its use . The resistance detected against drugs currently employed has led to a renewed interest in streptomycin . Its mechanism of action is centered on the ribosome, inhibiting the protein synthesis of the microbacteria . Resistance appears when mutations in the genes codifying for rRNA 16S and for protein S12 are produced . We studied the use of streptomycin against 899 M . tuberculosis strains, 713 of which were from pulmonary and 186 from extrapulmonary isolates . The BACTEC 460 TB system was initially employed as was the ESP II system . As controls, the ATCC27294 pattern strains (susceptible to streptomycin, rifampicin, ethambutol and isoniazid) were used . The results showed 2.1% secondary resistance in all the cases . Multiresistance was observed in 12 strains. Crit Care Med, 2003 Aug, 31(8), 2228 - 37 Intensive care unit management of intra-abdominal infection; Marshall JC et al.; OBJECTIVE: To review the biologic characteristics of, and management approaches to, intra-abdominal infection in the critically ill patient . DESIGN: Narrative review . SETTING: Medline review focussed on intra-abdominal infection in the critically ill patient . PATIENTS AND SUBJECTS: Restricted to studies involving human subjects . INTERVENTIONS: None . RESULTS: Intra-abdominal infections are an important cause of morbidity and mortality in the intensive care unit (ICU) . Peritonitis can be classified as primary, secondary, or tertiary, the unique pathologic features reflecting the complex nature of the endogenous gut flora and the gut-associated immune system, and the alterations of these that occur in critical illness . Outcome is dependent on timely and accurate diagnosis, vigorous resuscitation and antibiotic support, and decisive implementation of optimal source control measures, specifically the drainage of abscesses and collections of infected fluid, the debridement of necrotic infected tissue, and the use of definitive measures to prevent further contamination and to restore anatomy and function . CONCLUSIONS: Optimal management of intra-abdominal infection in the critically ill patient is based on the synthesis of evidence, an understanding of biologic principles, and clinical experience . An algorithm outlining a clinical approach to the ICU patient with complex intra-abdominal infection is presented. Laryngoscope, 2003 Sep, 113(9), 1503 - 7 Invasive fungal and bacterial infections of the temporal bone; Marzo SJ et al.; OBJECTIVES/HYPOTHESIS: Objectives were to highlight the importance of surgical therapy in treating invasive polymicrobial infections of the temporal bone, to discuss the importance of antifungal therapy, and to review the differential diagnosis of ear canal granulomatous disorders . STUDY DESIGN: Retrospective case review at a tertiary care medical center . METHODS: A retrospective chart review of all patients diagnosed with invasive polymicrobial temporal bone infections was performed . Four patients were identified . All patients required surgical therapy for definitive management . All patients were followed for at least 1 year or until death . RESULTS: Three of four patients had invasive fungi as pathogens . One patient had an occult squamous cell carcinoma . At the time of writing, one patient was free of disease, two were dead of disease, and one was alive with disease . CONCLUSION: Invasive polymicrobial temporal bone infections can occur in immunocompromised patients and can possibly harbor an occult malignancy . Surgical debridement may be necessary to arrive at a correct diagnosis . Modified radical mastoidectomy with parenteral antibiotic therapy and other adjunctive measures may be necessary for disease resolution. Best Pract Res Clin Obstet Gynaecol, 2003 Oct, 17(5), 795 - 809 Induction of labour with a favourable cervix and/or pre-labour rupture of membranes; Crane JM et al.; Premature rupture of membranes (PROM) occurs in 8% of term deliveries . In this situation labour induction with prostaglandins, compared with expectant management, results in a reduced risk of chorioamnionitis, neonatal antibiotic therapy, neonatal intensive care (NICU) admission, and increased maternal satisfaction . The use of prostaglandin is associated with an increased rate of diarrhoea and use of analgesia/anaesthesia . Compared with oxytocin, prostaglandin induction results in a lower rate of epidural use and internal fetal heart rate monitoring but a greater risk of chorioamnionitis, nausea, vomiting, more vaginal examinations, neonatal antibiotic therapy, NICU admission and neonatal infection . Women should be informed of the risks and benefits of each method of induction.Misoprostol is gaining increasing interest as an alternative induction agent . It appears to be an effective method of labour induction with term PROM . Further research is needed to identify the preferred dosage, route and interval of administration, and to assess uncommon maternal and neonatal outcomes.There has been limited research on the use of prostaglandins, including misoprostol, for induction of labour with a favourable cervix and intact membranes . Compared with intravenous oxytocin (with and without amniotomy), labour induction using vaginal prostaglandins in women with a favourable cervix (with and without PROM) results in a higher rate of vaginal delivery within 24 hours and increased maternal satisfaction . In women with a favourable cervix, artificial rupture of membranes followed by oral misoprostol has similar time to vaginal delivery compared with artificial rupture of membranes followed by oxytocin . Further research with prostaglandins, including misoprostol, is needed to evaluate other maternal and neonatal outcomes in women being induced with a favourable cervix.No form of prostaglandin induction in women with PROM or favourable cervix has proven clearly superior to oxytocin infusion. Clin Transpl . 2002;:137-42. Kidney transplantation at UCLA; Gritsch HA et al.; The demand for renal transplantation continues to increase . Combined organ transplantation currently accounts for approximately 10% of the kidney transplants at UCLA . As the demand for renal transplantation has increased, living kidney donation has become more common and achieves excellent results . Thirty-five percent of the 1,307 renal transplants at UCLA during the past 5 years were from living donors . The donor morbidity has been reduced with improvements in postoperative analgesia and laparoscopic nephrectomy techniques . Management of the patients waiting for cadaveric renal transplantation is becoming increasingly complex, since this population now exceeds 1,000 patients and the median waiting time is approaching 5 years . Improved immunosuppressive,