Antibiotics

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, antibiotic, and antiviral medications have significantly reduced the rate of acute rejection and serious infections . As long-term graft survival improves, the side effect profiles of newer medications are increasingly important . The one- and 3-year graft survival rates during the past 5 years were 98% and 90% for adult recipients of living donor kidneys and were 91% and 82% for recipients of cadaveric grafts, respectively . The results for pediatric transplants were 100% and 97% for living donor kidneys and 97% and 85% for cadaveric grafts at one and 3 years, respectively . We are pleased with our excellent results and the manner in which our program has responded to changes in the organ transplant environment.

J Pharmacol Exp Ther, 2003 Nov, 307(2), 626 - 32 Epub 2003 Sep 11.
Altered diurnal rhythm of intestinal peptide transporter by fasting and its effects on the pharmacokinetics of ceftibuten; Pan X et al.; We previously demonstrated that H+/peptide cotransporter PEPT1 shows a diurnal rhythm in the rat small intestine . In the present study, we examined the effect of food intake on the diurnal rhythm of intestinal PEPT1 using fed and fasted rats and also determined whether such variation affected the pharmacokinetics of peptide-like drugs . In fed rats, PEPT1 protein level was significantly higher at 8:00 PM than at 8:00 AM . However, during fasting for 2 to 4 days, the differences of PEPT1 protein levels between 8:00 AM and 8:00 PM gradually disappeared . Intestinal absorption of an oral antibiotic ceftibuten (CETB), a pharmacological substrate for PEPT1, was also greater at 8:00 PM than at 8:00 AM in fed rats, but not different in 4-day fasted rats . In contrast to PEPT1 protein levels, PEPT1 mRNA levels retained a diurnal rhythm after 4 days of fasting . Pharmacokinetic analyses of CETB after intraintestinal administration demonstrated that both Cmax and area under the plasma concentration-time curve from 0 to 3 h were greater at 8:00 PM than at 8:00 AM in fed rats . In contrast, pharmacokinetic parameters showed no significant difference between 8:00 AM and 8:00 PM for intraintestinal administration in 4-day fasted rats and for intravenous administration in fed and 4-day fasted rats . These findings suggested that the diurnal rhythm of intestinal PEPT1 transport activity was disrupted by fasting and that diurnal variation of intestinal PEPT1 functionality could influence the pharmacokinetics of peptide-like drugs such as CETB.

Perit Dial Int, 2003 Jul-Aug, 23(4), 368 - 74
The efficacy of silver-ion implanted catheters in reducing peritoneal dialysis-related infections; Crabtree JH et al.; BACKGROUND: Dialysis-related infections are the commonest cause of catheter loss and transfer to hemodialysis . Surface modifications of the catheter that reduce infections are of major importance . OBJECTIVE: The efficacy of silver-ion treated catheters in reducing dialysis-related infections was tested . METHODS: The study design was a prospective, randomized controlled trial . Patients were implanted with either a silver-treated study catheter or a control catheter . Prospective collection of data included infectious complications and catheter survival . RESULTS: The subject groups were comprised of 67 silver-treated catheters and 72 control catheters . Demographic characteristics of the study and control groups were equal . Exit-site infection rates for the study group and control group (0.52 and 0.45 episodes/patient-year of dialysis respectively) were not different by Poisson regression analysis (p > 0.4) . Peritonitis rates were identical for the two groups (0.37 episodes/patient-year) and were not different by Poisson analysis (p > 0.9) . Antibiotic-free intervals between infections for the study and control groups were not significantly different for exit-site infections (p = 0.58), peritonitis (p = 0.44), or both infections combined (p = 0.47) . Actuarial analyses showed no differences between the groups in the probability of remaining free of exit-site infection (p > 0.2) or peritonitis (p > 0.7) . Similarly, catheter survival was not significantly different between the groups (p > 0.6) . CONCLUSION: Surface modification of catheters with ion beam implantation of silver produced no clinical effect with respect to reducing dialysis-related infections.

Hinyokika Kiyo, 2003 Jul, 49(7), 419 - 21
{A case of delayed infection of a pelvic lymphocele following radical prostatectomy 4 months after operation}; Nakano M et al.; Symptomatic lymphocele presented after pelvic lymphadenectomy for localized carcinoma of the prostate is a relatively rare complication . We treated a case of infected lymphocele presenting 4 months after a limited staging pelvic lymphadenectomy and a radical prostatectomy for adenocarcinoma of the prostate . The patient was a 70-year-old Japanese man having the chief complaint of fever, right lower abdominal pain, nausea and vomiting . Pelvic computed tomography showed a 14 cm cystic mass with a thick capsule on the right iliopsoas muscle . It was suspected to be an infected lymphocele . After percutaneous drainage, sclerotherapy (povidone iodine, minocycline and ethanol) and antibiotic drugs, the infected lymphocele was resolved.

Pharmacol Res, 2003 Nov, 48(5), 461 - 5
Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart; Abdel-Wahab MH et al.; The therapeutic value of doxorubicin (DOX) as anticancer antibiotic is limited by its cardiotoxicity . The implication of natural phenolic acids in the prevention of many pathologic diseases has been reported . Herein, the ability of p-coumaric (PC) acid, a member of phenolic acids, to protect rat's heart against DOX-induced oxidative stress was investigated . Three main groups of albino rats were used; DOX, PC, and PC plus DOX-receiving animals . Corresponding control animals were also used . DOX was administered i.p . in a single dose of 15mgkg(-1) . PC alone, in a dose of 100mgkg(-1), was orally administered for five consecutive days . In PC/DOX group, rats received PC 5 days prior to DOX . DOX-induced high serum levels of lactic dehydrogenase (LDH) and creatine phosphokinase (CPK), were reduced significantly by PC administration, compared to DOX-receiving rats . Pretreatment with PC ameliorated the cardiac content of glutathione (GSH), and superoxide dismutase (SOD) & catalase (CAT) activities, compared to DOX-receiving rats . On the other hand, accumulation of cardiac content of MDA significantly decreased following PC pretreatment, compared to DOX-treated rats . The data presented here indicate that PC protects rats hearts against DOX-induced oxidative stress in the heart . It may be worthy to consider the usefulness of PC as adjuvant therapy in cancer management.

Chembiochem, 2003 Sep 5, 4(9), 821 - 8
The blasticidin S biosynthesis gene cluster from Streptomyces griseochromogenes: sequence analysis, organization, and initial characterization; Cone MC et al.; Blasticidin S is a potent antifungal and cytotoxic peptidyl nucleoside antibiotic from Streptomyces griseochromogenes . The mixed biosynthesis of the compound is evident from the three distinct structural components: a cytosine base, an amino deoxyglucuronic acid, and N-methyl beta-arginine . The blasticidin S biosynthesis gene cluster was cloned from S . griseochromogenes and the pathway heterologously expressed in S . lividans from a cosmid harboring a 36.7-kb fragment of S . griseochromogenes DNA . The complete DNA sequence of this insert has now been determined and evidence suggests a contiguous 20-kb section defines the blasticidin S biosynthesis cluster . The predicted functions of several open reading frames are consistent with the expected biochemistry and include an arginine 2,3-aminomutase, a cytosylglucuronic acid synthase, and a guanidino N-methyltransferase . Insight into other steps in the assembly of blasticidin S was evident from sequence homology with proteins of known function and heterologous expression of fragments of the cluster . Additionally, the gene that directs the production of free cytosine, blsM, was subcloned and expressed in Escherichia coli . Characterization of BlsM revealed that cytidine monophosphate serves as the precursor to cytosine.

Arch Ophthalmol, 2003 Sep, 121(9), 1279 - 82
Noninfectious endophthalmitis associated with intravitreal triamcinolone injection; Roth DB et al.; BACKGROUND: Intravitreal injection of triamcinolone has been advocated to treat exudative macular diseases such as macular edema and choroidal neovascularization . OBJECTIVE: To describe 7 patients who developed a clinical picture simulating endophthalmitis after intravitreal triamcinolone injection . METHODS: Intravitreal triamcinolone injections were performed to treat refractory cystoid macular edema or diffuse macular edema associated with diabetic retinopathy, macular pucker, branch retinal vein occlusion, or pseudophakia . One patient received an injection in an attempt to treat exudation associated with occult choroidal neovascularization . RESULTS: Preinjection visual acuity ranged from 20/50 to 20/400 . An extensive inflammatory response developed 1 to 2 days after injection in all 7 eyes . Five eyes had previously undergone vitrectomy . Four eyes had a layered hypopyon . All 7 eyes had an anterior chamber cellular reaction and vitritis . Visual acuity ranged from 20/400 to hand movements . The first 6 patients were treated for presumed endophthalmitis with vitreous cultures and intravitreal injections of antibiotics . All 6 cultures were negative for any organisms, and the eyes resolved their inflammatory response, with recovery to preinjection visual acuity or better . The seventh patient was treated with topical prednisolone without antibiotic therapy, and the inflammation resolved, with resolution of the macular edema seen before the intravitreal triamcinolone injection . CONCLUSION: It may be appropriate to closely observe noninfectious, toxic endophthalmitis in patients treated with intravitreal triamcinolone before assuming it to be infectious, especially in the absence of eye pain.

Arch Pediatr Adolesc Med, 2003 Sep, 157(9), 861 - 6
The use of osteopathic manipulative treatment as adjuvant therapy in children with recurrent acute otitis media; Mills MV et al.; OBJECTIVE: To study effects of osteopathic manipulative treatment as an adjuvant therapy to routine pediatric care in children with recurrent acute otitis media (AOM) . STUDY DESIGN: Patients 6 months to 6 years old with 3 episodes of AOM in the previous 6 months, or 4 in the previous year, who were not already surgical candidates were placed randomly into 2 groups: one receiving routine pediatric care, the other receiving routine care plus osteopathic manipulative treatment . Both groups received an equal number of study encounters to monitor behavior and obtain tympanograms . Clinical status was monitored with review of pediatric records . The pediatrician was blinded to patient group and study outcomes, and the osteopathic physician was blinded to patient clinical course . MAIN OUTCOME MEASURES: We monitored frequency of episodes of AOM, antibiotic use, surgical interventions, various behaviors, and tympanometric and audiometric performance . RESULTS: A total of 57 patients, 25 intervention patients and 32 control patients, met criteria and completed the study . Adjusting for the baseline frequency before study entry, intervention patients had fewer episodes of AOM (mean group difference per month, -0.14 {95% confidence interval, -0.27 to 0.00}; P =.04), fewer surgical procedures (intervention patients, 1; control patients, 8; P =.03), and more mean surgery-free months (intervention patients, 6.00; control patients, 5.25; P =.01) . Baseline and final tympanograms obtained by the audiologist showed an increased frequency of more normal tympanogram types in the intervention group, with an adjusted mean group difference of 0.55 (95% confidence interval, 0.08 to 1.02; P =.02) . No adverse reactions were reported . CONCLUSIONS: The results of this study suggest a potential benefit of osteopathic manipulative treatment as adjuvant therapy in children with recurrent AOM; it may prevent or decrease surgical intervention or antibiotic overuse.

Food Chem Toxicol, 2003 Nov, 41(11), 1447 - 52
Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research; Ali BH; Despite its nephrotoxic potential, the aminoglycoside antibiotic gentamicin (GM) is still considered to be an important agent against life-threatening infections . The goal of reducing or protecting against its nephrotoxicity has attracted much effort and attention during the last decade . This article reviews some of the literature published during the last decade on the effects of agents that ameliorate or augment GM nephrotoxicity . Notable among the ameliorating agents are antioxidant agents . These include different classes of compounds that include beta blockers (e.g . carvedilol), superoxide dismutase mimetic agents (e.g . M40403), hormones (e.g . melatonin), iron chelators (e.g . deferrioxamine), vitamins (vitamin C and E) and medicinal plants (e.g . garlic) . Other ameliorating agents include antibiotics (e.g . ceftriaxone), antiplatelet drugs (e.g . trapidil) and Ca++ agents that may augment GM nephrotoxicity include cyclosporin and the Ca++-channel blocker verapamil.

Transplant Proc, 2003 Aug, 35(5), 1684 - 5
Transvascular ethanol embolization: first option for the management of symptomatic nonfunctioning renal allografts left in situ; Delgado P et al.; BACKGROUND: Transplantectomy has been the conventional therapy for symptomatic failed grafts left in situ (FGLIS) . Graft intolerance syndrome (GIS) is a common complication after withdrawal of immunosuppression . Our group first reported transvascular ethanol embolization (TVEE) as an alternative for the management of GIS . OBJECTIVE: Our goal was to evaluate the efficacy and safety of TVEE in a large series of patients with symptomatic FGLIS . PATIENTS AND METHODS: From January 1989 to December 2001, 944 patients received cadaveric renal transplants in our center . During this period, 59 patients with FGLIS underwent TVEE (50+/-7 years, 71% men, 15% diabetics) . TVEE was performed using a transfemoral approach . A balloon occlusion catheter was inflated in the renal artery before ethanol injection (10-12 cc) . The position of coils completed the procedure . No systematic prophylactic antibiotic or steroid treatment was administered . RESULTS: The main indication for TVEE was GIS (51 patients, 86%) . TVEE was initially successful in 39 patients (66%) . A second TVEE, which was performed in 9 of 20 unresolved cases, was successful in six . After a second TVEE, the efficacy increased to 76% . The most frequent complication was postembolization syndrome (62%), which was manifested by fever, local pain, and inflammation that generally resolved in 48-72 hours . No major complications or deaths were observed . One of four patients underwent transplantectomy . Histologic examination of the removed graft showed renal tissue necrosis (10 cases) and pyonephrosis (4 cases) . CONCLUSIONS: TVEE, a safe and effective technique, may be considered as the treatment of choice for symptomatic FGLIS.

Curr Gastroenterol Rep, 2003 Oct, 5(5), 365 - 72
Small bowel bacterial overgrowth: presentation, diagnosis, and treatment; Singh VV et al.; Small bowel bacterial overgrowth (SBBO) syndrome is associated with excessive numbers of bacteria in the proximal small intestine . The pathology of this condition involves competition between the bacteria and the human host for ingested nutrients . This competition leads to intraluminal bacterial catabolism of nutrients, often with production of toxic metabolites and injury to the enterocyte . A complex array of clinical symptoms ensues, resulting in chronic diarrhea, steatorrhea, macrocytic anemia, weight loss, and less commonly, protein-losing enteropathy . Therapy is targeted at correction of underlying small bowel abnormalities that predispose to SBBO and appropriate antibiotic therapy . The symptoms and signs of SBBO can be reversed with this approach.

Arch Esp Urol, 2003 Jul-Aug, 56(6), 713 - 26
{The Sixth Framework Program for Research of the EU (2002-2006) . Opportunities for biomedical research}; Quintana i Trias O et al.; The Framework Program for Research and Technological Development constitutes the main instrument the European Union has had for financing research since 1984 . The current Sixth Framework Program (6FP), that covers the period 2002-2006, includes clinical research among the activities subsidized at the European level . Other research activities in the field of medicine, particularly genomics and research activities connecting basic knowledge generation with its applications in the field of health also receive a special emphasis . Examples of topics open to project presentation during the framework program are: research on cancer, both at the basic and applied and clinical levels, new diagnostic techniques, new drugs, and the fight against antibiotic resistances . Among the various types of projects that have room within the 6FP, the networks of excellence (NoE) and integrated projects (IP) stand out for their importance and their effect giving structure to the European research . Both try to reunite a critical mass of researchers and resources, to generate knowledge in the case of the IPs, and to interconnect experts to strengthen and extend the excellence in a specific research topic in the case of the NoE . Both these and the more modest traditional instruments require participation of groups from different countries in a consortium, mainly from the European Community countries . The process of evaluation is carried out looking at relevance criteria, scientific excellence, potential impact, and quality of the consortium, among others . Spanish researchers, among others, are wellcome to participate in the consortiums, coordinate projects and also to assist as experts in the evaluations.

Am J Kidney Dis, 2003 Sep, 42(3), 567 - 74
The clinical course of culture-negative peritonitis complicating peritoneal dialysis; Szeto CC et al.; BACKGROUND: Culture-negative peritonitis is a serious complication in peritoneal dialysis patients . METHODS: We studied all consecutive episodes of culture-negative peritonitis in our unit from 1995 to 2001 . We identified 1,182 episodes of peritonitis recorded; 212 episodes in 149 patients had negative culture results . RESULTS: The overall primary response rate was 67.5%, and the complete cure rate was 37.7% . In 95 episodes (44.8%), technical problems during the collection of dialysis effluent were suspected . There was a history of antibiotic therapy within 30 days before the onset in 56 episodes (26.4%) . Recent antibiotic therapy was associated with a lower primary response rate (31 of 56 versus 113 of 156 episodes; P = 0.019) and lower complete cure rate (12 of 56 versus 68 of 156 episodes; P = 0.003) . Furthermore, a history of peritonitis from 31 to 120 days before the onset also was associated with a lower complete cure rate (P = 0.001) . Multivariate analysis showed that recent peritonitis was the only independent predictor of treatment failure (odds ratio, 2.87; 95% confidence interval, 1.56 to 5.29) . CONCLUSION: Most of the culture-negative peritonitis could be explained by recent antibiotic therapy or technical problems during dialysate culture . Recent peritonitis and antibiotic therapy are associated with a poor treatment response . Early Tenckhoff catheter removal is recommended in this group of patients.

Anaesthesist, 2003 Aug, 52(8), 690 - 6
{Periodic surveillance of nosocomial infections in two neurology intensive care units . A valuable tool for quality management in intensive care}; Zolldann D et al.; BACKGROUND AND OBJECTIVE: Nosocomial infections are a common problem in intensive care therapy and have relevant influence on morbidity, mortality and associated costs . The aim of this study was to assess data on the epidemiology of nosocomial infections and related risk factors in neurological intensive care patients and to use them for internal quality management . METHODS: Prospective periodic surveillance was performed in the first quarter of the years 1999 and 2000 in two neurology intensive care units . RESULTS: Within the surveillance period, 340 patients with 2443 patient days and a mean length of stay 7,6 days were enrolled . A total of 63 nosocomial infections were identified in 51 patients . In comparison with national reference data, device utilisation rates as well as device-associated nosocomial infection rates were on a higher level . By timely and interpretative feedback of the surveillance data, for the first time the unit-specific nosocomial infection situation was made clear for the ward staff . As a result, different quality management activities like establishment of evidence-based infection control guidelines, continuous surveillance for pneumonia and optimisation of empirical antibiotic therapy were initiated in both units . CONCLUSION: The establishment of periodic surveillance proved to be a valuable tool for the promotion of quality management activities in both intensive care units.

J Bone Joint Surg Am, 2003 Sep, 85-A(9), 1667 - 72
Syme ankle disarticulation in patients with diabetes; Pinzur MS et al.; BACKGROUND: Syme ankle disarticulation is an amputation level that minimizes disability and preserves function, but it has been used sparingly in patients with diabetes mellitus . Surgeons have avoided this level because of the perceived high risk for wound failure, wound infection, or migration of the heel pad, which makes prosthesis use difficult . METHODS: Ninety-seven adult patients with diabetes mellitus who underwent Syme ankle disarticulation because of a neuropathic foot with an infection or gangrene, or both, during an eleven-year period were studied retrospectively . Selection of the amputation level was made on the basis of clinical examination and an assessment of the wound-healing parameters, i.e., vascular inflow, tissue nutrition, and immunocompetence . The average age of the patients was 53.2 +/- 17.5 years . RESULTS: Eighty-two patients (84.5%) ultimately achieved wound-healing . When threshold levels for vascular inflow (ultrasound Doppler ischemic index of 0.5 or transcutaneous partial pressure of oxygen between 20 and 30 mm Hg) and tissue nutrition (serum albumin of 2.5 g/dL) were met, an overall success rate of 88% was achieved . Total lymphocyte count (an absolute lymphocyte count of 1500) and the smoking of cigarettes during the study period did not appear to impact wound-healing rates . The overall infection rate was 23%, and it was three times greater in smokers . Most infections were managed with local wound care and antibiotic therapy . At a minimum follow-up of two years, all but two patients were able to walk with a prosthesis . Thirty of the ninety-seven patients died at an average of 57.1 months following surgery . CONCLUSIONS: The results of this retrospective review support the value of Syme ankle disarticulation in diabetic patients with infection or gangrene . This function-sparing amputation can be successfully performed with a reasonable risk . Patients managed with a Syme ankle disarticulation appeared to remain able to walk better and to survive longer than similar patients who had a transtibial amputation and served as historical controls . In diabetic patients with dysvascular disease who have adequate vascular inflow to support wound-healing (an ultrasound Doppler ischemic index of 0.5 or a transcutaneous partial pressure of oxygen between 20 and 30 mm Hg), the threshold for the wound-healing parameter of serum albumin appears to be as low as 2.5 g/dL.

Chem Biol, 2003 Aug, 10(8), 751 - 8
Sequence specificity, reactivity, and antitumor activity of DNA-alkylating pyrrole-imidazole diamides; Bando T et al.; Three conjugates of imidazole (Im)-pyrrole (Py) diamide and a DNA-alkylating moiety derived from the antibiotic duocarmycin A were synthesized, and their sequence specificity, reactivity, and antitumor activity comparatively examined . Sequencing gel analysis indicated that ImPyDu (1) alkylates DNA at the 3' end of AT-rich sequences at micromolar concentration . ImPyDu86 (2) reacts with DNA at AT-rich sites together with dialkylation sites at micromolar concentration . ImPyLDu86 (3) efficiently alkylates dialkylation sites at nanomolar concentration . Average values of log IC(50) against a 39 cancer cell line panel of 1-3 were -4.59, -5.95, and -8.25, respectively . The differential growth inhibition pattern of 1-3 varied with relatively low correlation coefficients . Array-based gene expression monitoring was performed for 3 in a human lung cancer cell line . Substantial downregulation of expression was seen for genes involved in DNA damage response, transcription, and signal transduction.

J Hand Surg {Br}, 2003 Oct, 28(5), 388 - 94
The use of prophylactic flucloxacillin in treatment of open fractures of the distal phalanx within an accident and emergency department: a double-blind randomized placebo-controlled trial; Stevenson J et al.; Open fractures of the distal phalanx commonly present to the Accident and Emergency Department . Controversy surrounds the use of prophylactic antibiotics in treating this injury . A double-blind, prospective, randomized placebo-controlled study was undertaken comparing the use of prophylactic flucloxacillin to placebo in addition to meticulous wound toilet . One hundred and ninety-three adult patients with an open fracture of the distal phalanx were studied . Seven patients developed superficial infections, an overall infection rate of 4% . No patient developed osteitis or a deep wound infection . There were three cases of infection in the 98 patients (3%) in the antibiotic group and four cases of infection in the 95 patients (4%) in the placebo group . A difference of proportion test confirmed no significant difference . It is concluded that the addition of prophylactic flucloxacillin to thorough wound toilet and careful soft-tissue repair of open fracture of the distal phalanx confers no benefit.

Scand J Infect Dis, 2003, 35(6-7), 422 - 4
A woman with a lobar infiltrate due to psittacosis detected by polymerase chain reaction; Heddema ER et al.; This report presents a case of community-acquired pneumonia due to Chlamydia psittaci presenting with a lobar infiltrate and diagnosed by a newly developed ompA gene-based polymerase chain reaction (PCR) . This gene encodes a specific C . psittaci major outer membrane protein . This kind of PCR could reduce antibiotic consumption and expedite outbreak management.

Acta Otolaryngol, 2003 Aug, 123(6), 737 - 40
Craniocervical necrotizing fasciitis secondary to parotid gland abscess; Marioni G et al.; Necrotizing fasciitis is a potentially fatal soft-tissue infection that predominantly affects the abdominal wall, perineum and extremities . It is an uncommon clinical entity in the head and neck region and an exhaustive review of the English language literature disclosed reports on approximately 160 cases . Dental pathology, post-traumatic or iatrogenic skin or mucosa injuries and parapharyngeal or peritonsillar infections were the most frequently described origins . We describe herein the first case of craniocervical necrotizing fasciitis (CCNF) due to a parotid gland abscess . The patient was successfully treated with i.v . broad-spectrum antibiotic therapy and an aggressive surgical approach (drainage of the parotid abscess and exploration of the neck, with drainage and debridement of necrotic tissue) . Effective management of CCNF depends on a prompt diagnosis . Intravenous broad-spectrum antibiotic therapy should be instituted immediately . Antibiotic coverage can be narrowed once the culture results are obtained . Aggressive surgical intervention is necessary, involving wide incision, adequate exploration of deep neck spaces and debridement of necrotic tissue until healthy bleeding tissue is encountered.

J Am Chem Soc, 2003 Sep 10, 125(36), 10810 - 21
Spectroscopic studies of the interaction of ferrous bleomycin with DNA; Kemsley JN et al.; Bleomycin is an antibiotic used in cancer chemotherapy for its ability to achieve both single- and double-strand cleavage of DNA through abstraction of the deoxyribose C4'-H . Magnetic circular dichroism (MCD) and X-ray absorption (XAS) spectroscopies have been used to study the interaction of the biologically relevant FeIIBLM complex with DNA . Calf thymus DNA was used as the substrate as well as short oligonucleotides, including one with a preferred 5'-G-pyrimidine-3' cleavage site {d(GGAAGCTTCC)2} and one without {d(GGAAATTTCC)2} . DNA binding to FeIIBLM significantly perturbs the FeII active site, resulting in a change in intensity ratio of the d d transitions and a decrease in excited-state orbital splitting (5Eg) . Although this effect is somewhat dependent on length and composition of the oligonucleotide, it is not correlated to the presence of a 5'-G-pyrimidine-3' cleavage site . No effect is observed on the charge-transfer transitions, indicating that the H-bonding recognition between the pyrimidine and guanine base does not perturb Fe-pyrimidine backbonding . Azide binding studies indicate that FeIIBLM bound to either oligomer has the same affinity for N3- . Parallel studies of BLM structural derivatives indicate that FeIIiso-PEPLM, in which the carbamoyl group is shifted on the mannose sugar, forms the same DNA-bound species as FeIIBLM . In contrast, FeIIDP-PEPLM, in which the -aminoalanine group is absent, forms a new species upon DNA binding . These data are consistent with a model in which the primary amine from the -aminoalanine is an FeII ligand and the mannose carbamoyl provides either a ligand to the FeII or significant second-sphere effects on the FeII site; intercalation of the bithiazole tail into the double helix likely brings the metal-bound complex close enough to the DNA to create steric interactions that remove the sugar groups from interaction with the FeII . The fact that the FeII active site is perturbed regardless of DNA sequence is consistent with the fact that cleavage is observed for both 5'-GC-3' and nonspecific oligomers and indicates that different reaction coordinates may be active, depending on orientation of the deoxyribose C4'-H.

Leuk Lymphoma, 2003 Aug, 44(8), 1413 - 6
Mucosa-associated lymhpoid tissue (MALT) lymphoma of the jejunum and Helicobacter pylori--chance association?
Keung YK, Higgs V, Albertson DA, Cappellari JO.
Helicobacter pylori have been causally linked to primary gastric B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type . Antibiotic therapy to eradicate H . pylori has been shown to induce remission of such lymphoma . We report a case of primary B-cell MALT lymphoma of the jejunum associated with H . pylori . The literature of intestinal MALT lymphoma is reviewed.

Vet Ophthalmol, 2003 Sep, 6(3), 191 - 5
Nonulcerative keratouveitis as a manifestation of Leptospiral infection in a horse; Wada S et al.; A 2-year-old Thoroughbred filly presented with ocular pain and epiphora of the left eye . The pupil was miotic and the cornea edematous near the ventro-temporal limbus, but did not retain any fluorescein . The topical antibiotics and atropine and diclofenac, and systemic flunixin meglumine and antibiotic therapy did not resolve the condition . A pink and fleshy infiltrate developed near the limbus indicating nonulcerative keratouveitis . The anterior uveitis deteriorated as manifested by the presence of dyscoria, hypopyon, and organized fibrin in the anterior chamber . Ocular signs were improved by topical and subconjunctival corticosteroids, but repeatedly deteriorated as the frequency of medication was reduced . The horse was seropositive to three serovars of Leptospira interrogans . The animal was diagnosed as blind on day 91 by the absence of pupillary light and menace reflexes, and donated for histopathologic diagnosis . The corneal opacity was histologically fibrotic and infiltrated predominantly by lymphocytes with Descemet's membrane partially disrupted by macrophages . The choroid was infiltrated by lymphocytes, eosinophils and basophils, and was positive to IgG and C3 . There were filamentous or spiral structures positive to Warthin-Starry stain in the renal cortex . There was also polymerase chain reaction amplification of the leptospiral gene in the kidney . From these findings nonulcerative keratouveitis was believed to be caused by systemic infection with Leptospira.

Andrologia, 2003 Aug, 35(4), 244 - 7
Treatment with levofloxacin does not resolve asymptomatic leucocytospermia--a randomized controlled study; Krisp A et al.; The manual of the World Health Organization defines leucocytospermia as the presence of >1 x 10(6) white blood cells per ml semen . Most authors consider leucocytospermia to be a consequence of inflammation due to bacterial infection . However, the efficacy of antibiotic therapy was not unequivocally demonstrated until now . We started a prospective, randomized, controlled study in 36 patients, who consulted our department for infertility with leucocytospermia . None of the patients reported any symptoms of genital infection . The patients were assigned randomly to two groups: group 1 received 250 mg levofloxacin once a day over 10 days, patients of group 2 received no therapy . Semen analysis was repeated 2 weeks later . After administration of levofloxacin, a mean decrease of leucocyte count of 45.8 +/- 72.2% compared with a decrease of only 3 +/- 109.2% in the untreated group was observed . However, this difference is not statistically significant . There were no significant differences between the two groups with respect to leucocyte count, sperm count and sperm cell after treatment . We conclude from our study that antibiotic therapy does not provide benefit for treatment of asymptomatic leucocytospermia.

Bull Exp Biol Med, 2003, 135 Suppl 1, 52 - 3
Modification of chemotherapeutic activity in adriablastine with the synthetic antioxidant in low doses; Pal'mina NP et al.; Synthetic antioxidant potassium phenosan in ultralow doses administrated in combination with antitumor antibiotic adriamycin in a therapeutic dose (8 mg/kg) markedly prolonged the mean life span of tumor-bearing animals compared to adriamycin monotherapy . This effect depended on the dose of antioxidant and was maximum at phenosan concentrations of 10(-17) and 10(-15) M . Potassium phenosan in these concentrations not only increased the mean life span, but also determined survival of 10-20% animals (as differentiated from adriamycin monotherapy).

Microbiology, 2003 Sep, 149(Pt 9), 2427 - 33
fusB is an allele of nadD, encoding nicotinate mononucleotide adenylyltransferase in Escherichia coli; Stancek M et al.; Isolation of the temperature-sensitive Escherichia coli mutant 72c has been described previously . The mutant allele was named fusB and causes a pleiotropic phenotype, the most striking features of which, besides temperature sensitivity, are the inability to grow on synthetic medium and supersensitivity to trimethoprim, an antibiotic that inhibits the C1 metabolism . This work shows that the fusB mutation is a frameshift mutation in the nadD gene that encodes nicotinate mononucleotide adenylyltransferase . The frameshift leads to a change of the last 10 amino acids and an addition of 17 amino acids . This lesion, renamed nadD72, leads to very little NAD+ and NADPH synthesis at the permissive temperature and essentially no synthesis at the non-permissive temperature . As a comparison, a new mutation in the nadD gene, with an amino acid change in the ATP-binding site, has been isolated . Its NAD+ synthesis is decreased at 30 degrees C but the level is still sufficient to support normal growth . At 42 degrees C, NAD+ synthesis is reduced further, which leads to temperature sensitivity on minimal medium . This mutation was designated nadD74 . Thus, a small decrease in NAD+ levels affects ability to grow on minimal medium at 42 degrees C, while a large decrease leads to a more pleiotropic phenotype.

Eur J Dermatol, 2003 Jul-Aug, 13(4), 396 - 8
Minocycline-induced cutaneous polyarteritis nodosa with antineutrophil cytoplasmic antibodies; Pelletier F et al.; Minocycline is an antibiotic widely used in the treatment of acne . Among the induced auto-immune disorders, cutaneous polyarteritis nodosa (PAN) is very rare . A new case is reported below . A 23-year-old female patient treated with minocycline for acne for 24 months developed sub-cutaneous nodules, livedo reticularis and pigmented lesions of the lower limbs . Antineutrophil cytoplasmic antibodies (ANCA) were positive at 1/320 . Skin biopsy showed vasculitis of a medium-sized artery . The role of minocycline was suspected using the imputability criteria . The diagnosis of minocycline-induced cutaneous PAN with ANCA was sustained . After withdrawal of the treatment, the nodular lesions decreased spontaneously, whereas livedo disappeared and inflammatory parameters were normalized after oral corticosteroid therapy . Minocycline is a tetracycline which is efficient for treating acne . Auto-immune disorders are frequently observed . Among them, it is very rare to observe cutaneous PAN associated with positive ANCA . The pathophysiological mechanisms are discussed.

Fungal Genet Biol, 2003 Oct, 40(1), 65 - 71
The development of a transformation system for the dimorphic plant pathogen Holleya sinecauda based on Ashbya gossypii DNA elements; Schade D et al.; We have developed a transformation system for the dimorphic plant pathogenic fungus Holleya sinecauda based on an electroporation protocol used for the closely related filamentous fungus Ashbya gossypii . DNA-mediated transformation of the dominant selection marker kanMX generated H . sinecauda transformants that were resistant to the antibiotic drug G418/geneticin . Freely replicating plasmids could be established in H . sinecauda using an A . gossypii autonomously replicating sequence (ARS) element, whereas Saccharomyces cerevisiae ARS elements, which are functional in A . gossypii, were not functional in H . sinecauda . In addition, centromeric DNA of A . gossypii stabilized the maintenance of plasmids in H . sinecauda under non-selective conditions . We isolated a fragment of the HsLEU2 gene and used this locus for targeted integration of kanMX3, consisting of the kanMX gene flanked by direct repeats . This allowed the construction of a Hsleu2 strain which became G418 sensitive after direct repeat-induced marker excision . The Hsleu2 strain can be complemented by the ScLEU2 gene . Finally, we constructed high- and low-copy shuttle vectors for H . sinecauda.

J Clin Neurosci, 2003 Sep, 10(5), 627 - 8
Delayed-onset pineal abscess following transsphenoidal surgery for pituitary adenoma: a case report; Ko Y et al.; A 41-year-old woman suffered fever, speech disturbance and confusion four months after transsphenoidal surgery for pituitary macroadenoma . Meanwhile, the patient had been well except for transient asymptomatic postoperative pneumocephalus without cerebrospinal fluid (CSF) rhinorrhoea . Brain computed tomographic scan revealed a peripherally enhancing pineal abscess which superimposed on a preexisting pineal cyst . CSF findings showed elevated leukocyte count and positive bacterial culture . Three weeks of intensive antibiotic therapy and surgical evacuation of the pineal abscess ensued . The patient showed restricted postoperative recovery with moderate hypothalamic dysfunction . A unique case of delayed-onset postoperative pineal abscess which complicates the preexisting asymptomatic pineal cyst is presented and the possible explanation for this is speculated with review of the available literatures.

Am J Surg, 2003 Sep, 186(3), 259 - 63
Revisiting the essential role of oxygen in wound healing; Gordillo GM et al.; Hypoxemia, caused by disrupted vasculature, is a key factor that limits wound healing . Correcting hypoxemia through the administration of supplemental oxygen (O(2)) can have significant beneficial impact on wound healing in the perioperative and outpatient settings . Beyond its role as a nutrient and antibiotic, O(2) may support vital processes such as angiogenesis, cell motility, and extracellular matrix formation . Recent discoveries highlight a novel aspect, addressing the role of O(2) in wound healing via the production of reactive oxygen species (ROS) . Almost all wound-related cells possess specialized enzymes that generate ROS (including free radicals and H(2)O(2)) from O(2) . Defect in these enzymes is associated with impaired healing . Low wound pO(2) is expected to compromise the function of these enzymes . At low concentrations, ROS serve as cellular messengers to support wound healing . The use of systemic hyperbaric O(2) therapy presents potential advantages, as well as risks . There is evidence to suspect that the use of pressure and systemic pure O(2) may not be essential in wound care . Elimination of these factors by using sub-pure systemic O(2) under normobaric conditions may significantly minimize the risk of O(2) toxicity . Furthermore, opportunities to treat dermal wounds using topical O(2) therapy warrant further investigation . Given that many growth factors require ROS for their function, it is reasonable to assume that approaches to correct wound pO(2) will serve as an effective adjunct in treating chronic wounds.

Quintessence Int, 2003 Jul-Aug, 34(7), 515 - 25
Dental management of patients with human immunodeficiency virus; Campo-Trapero J et al.; The demand for dental treatment by human immunodeficiency virus (HIV)-infected individuals is rising . Some professionals are still reluctant to treat these patients, despite the extremely low likelihood of professional transmission, which increases only in patients with a very elevated viral load . The complications rate after dental intervention is very low, even in patients with considerable immunologic deterioration . The dentist should pay special attention to the general clinical situation and immunologic and HIV virologic status of the seropositive patient, and to the presence of hemostasis alterations or of other concomitant diseases . Antiretroviral or any other drug treatments must also be recorded, in order to avoid possible interactions with clinician-prescribed drugs . Tooth extraction is the most common dental treatment and requires no antibiotic therapy except in cases of neutropenia or severe immunosuppression . Other dental treatments do not require special precautions, and the complications index among these patients is similar to that among the uninfected patient population . With this background, there is a need to make the clinician-in-training aware of the importance of regular dental health checkups as part of the health care routine of HIV-infected patients and to familiarize the clinician with their management, while not disregarding the unquestionable requirement to carry out the general and specific prevention measures to be adopted in all cases.

Org Biomol Chem, 2003 Jun 21, 1(12), 2084 - 95
Suzuki-Miyaura homocoupling of naphthyl triflates using bis(pinacolato)diboron: approaches to the biaryl skeleton of crisamicin A; Brimble MA et al.; Homocoupling of naphthyl triflates 27, 16, 17 to the respective binaphthyls 28, 31 and 35 has been achieved in a one-pot procedure using bis(pinacolato)diboron and PdCl2(dppf) . Use of potassium acetate as the base provides access to the initial naphthylboronate intermediates whereas the stronger base potassium phosphate is required in order to promote subsequent coupling of the naphthylboronate with a second equivalent of the naphthyl triflate . Attempts to convert binaphthyl 35 into bis-acetylnaphthalene 14, a key intermediate for the synthesis of the dimeric pyranonaphthoquinone antibiotic crisamicin A 2, via double Fries rearrangement of bis-acetate 37 derived from binaphthyl 35, were unsuccessful . Attempts to introduce the acetyl groups at C-7 and C-7' on bis-acetylnaphthalene 14 via Fries rearrangement of the monomeric precursors 21 and 15, before effecting homocoupling to a biaryl were unsuccessful . Introduction of an acetyl group via initial bromination ortho to the hydroxyl group in naphthol 18, which bears an electron rich benzyl ether at C-7, was plagued by the formation of phenolic coupling product 42 and naphthoquinone 43 . Bromination of naphthol 45, bearing a less electron rich triflate group at C-7, also afforded binaphthol 47 resulting from phenolic coupling as well as naphthoquinone 48 when using N-bromosuccinimide at low temperature.

Biophys J, 2003 Sep, 85(3), 1702 - 12
The effects of gramicidin on the structure of phospholipid assemblies; Szule JA et al.; Gramicidin is an antibiotic peptide that can be incorporated into the monolayers of cell membranes . Dimerization through hydrogen bonding between gramicidin monomers in opposing leaflets of the membrane results in the formation of an iontophoretic channel . Surrounding phospholipids influence the gating properties of this channel . Conversely, gramicidin incorporation has been shown to affect the structure of spontaneously formed lipid assemblies . Using small-angle x-ray diffraction and model systems composed of phospholipids and gramicidin, the effects produced by gramicidin on lipid layers were measured . These measurements explore how peptides are able to modulate the spontaneous curvature properties of phospholipid assemblies . The reverse hexagonal, H(II), phase formed by dioleoylphosphatidylethanolamine (DOPE) monolayers decreased in lattice dimension with increasing incorporation of gramicidin . This indicated that gramicidin itself was adding negative curvature to the lipid layers . In this system, gramicidin was measured to have an apparent intrinsic radius of curvature, R0pgram, of -7.1 A . The addition of up to 4 mol% gramicidin in DOPE did not result in the monolayers becoming stiffer, as measured by the monolayer bending moduli . Dioleoylphosphatidylcholine (DOPC) alone forms the lamellar (L(alpha)) phase when hydrated, but undergoes a transition into the reverse hexagonal (H(II)) phase when mixed with gramicidin . The lattice dimension decreases systematically with increased gramicidin content . Again, this indicated that gramicidin was adding negative curvature to the lipid monolayers but the mixture behaved structurally much less consistently than DOPE/gramicidin . Only at 12 mol% gramicidin in dioleoylphosphatidylcholine could an apparent radius of intrinsic curvature of gramicidin (R0pgram) be estimated as -7.4 A . This mixture formed monolayers that were very resistant to bending, with a measured bending modulus of 115 kT.

Ann Fr Anesth Reanim, 2003 Aug, 22 Suppl 1, 81s - 96s
{Lesions to lips, oral and nasal cavities, pharynx, larynx, trachea and esophagus due to endotracheal intubation and its alternatives}; Lacau Saint Guily J et al.; Dysphagia of greater than 48 h duration is an indication for indirect laryngoscopy and when odynophagia and otalgia occur simultaneously, the possibility of subluxation of the arytenoids demands an urgent ENT assessment . The potential seriousness of laryngeal lesions following intubation obliges us to use the smallest compatible endotracheal tube . The occurrence of pain cervical surgical emphysema and fever suggests a pharyngeal lesion necessitating the suspension of oral feeding and the initiation of antibiotic therapy with anaerobic activity, while awaiting possible surgical intervention . There is no argument to use a tooth-guard for each intubation, but tooth fragility must be researched . The incidence of nasal fossa trauma is reduced with the use of nasal packs impregnated with local anaesthetic containing a vasoconstrictor . This allows the introduction of a small flexible lubricated tube . Laryngeal mask-induced sore throat is more common than the more serious injuries . The classical technique of introducing a laryngeal mask of appropriate size (4 for women, 5 for men) in which the cuff is inflated to a leak pressure of 20 cm H(2)O reduces this frequency . The facial mask may cause injuries especially with prolonged use . The incidence of pulmonary aspiration, linked to the action of drugs, raised intra-abdominal pressure; an emergent situation or difficult intubation is decreased with the performance of the Sellick maneuver at intubation, rapid induction and the neutralization of gastric acidity . A meticulous technique of insertion of the, individualized anaesthesia, particular vigilance at the time of decurarisation and position changes and a calm awakening assure its optimal use, unless the Proseal laryngeal mask modifies this point of view.

Neurosurgery, 2003 Sep, 53(3), 749 - 52; discussion 752-3
Seeding of a cavernous angioma with Mycoplasma hominis: case report; House P et al.; OBJECTIVE AND IMPORTANCE: To describe a unique case of hematogenous seeding of a cavernous angioma with the commensal organism Mycoplasma hominis . CLINICAL PRESENTATION: A 40-year-old female patient presented with a severe headache and acute left facial nerve palsy . Imaging studies revealed a right frontal mass lesion with characteristics of a cavernous angioma . INTERVENTION: The patient underwent a craniotomy for cavernous angioma resection . Purulent material was noted at the time of resection, and no hemorrhage was observed . Despite antibiotic therapy, the patient required repeat craniotomies for subsequent abscess treatment . M . hominis was identified as the pathogen . CONCLUSION: M . hominis is a rare cause of brain abscesses and can be difficult to eradicate . Cavernous angiomas can be seeded hematogenously.

Folia Med (Plovdiv), 2003, 45(1), 13 - 9
Treatment with fluorated quinolones of febrile neutropenia in patients with hematologic malignancies; Nenova IS et al.; The use of fluoroquinolones in the treatment of cytotoxic therapy-induced febrile neutropenia is controversial . AIM: The aim of the study was to compare the therapeutic effect of fluoroquinolones with that of standard antibiotic regimens in patients with hematologic malignacies and febrile neutropenia following antineoplastic chemotherapy . PATIENTS AND METHODS: This is a prospective randomized study including 129 patients with 141 neutropenic episodes divided into two groups . Fluoroquinolones are used in the trial group and broad-spectrum beta-lactam antibiotics in the control group . The data are analyzed using alternative analysis, non-parametrical chi-square test and Student-Fisher t-test . RESULTS: The febrile neutropenic episodes were classified as fever of unknown origin (50.4%) and documented infection (49.6%) . In the category "fever of unknown origin" no statistically significant difference was found in the clinical effect, patient survival, general and infectious lethality between the trial and control group . In the category "documented infection" the trial group showed significantly lower therapeutic effect and lower infection-free survival of the patients . The clinical effect and infection-free survival after treatment with fluoroquinolones were significantly lower in the category "documented infection" than in the category "fever of unknown origin" . CONCLUSION: Fluoroquinolones can be alternative drugs to the standard antibiotic regimens in the treatment of febrile neutropenia in cases of fever of unknown origin . Fluoroquinolone monotherapy is not recommended in cases of febrile neutropenia with documented infection.

Mil Med, 2003 Aug, 168(8), 651 - 3
Cutaneous blastomycosis without evidence of pulmonary involvement; Clinton TS et al.; Blastomycosis is an infection that is often associated with recent military, occupational, or recreational activities near damp soil in various endemic regions, including the Great Lakes and major river valleys in the Midwest as well as various overseas regions . In the great majority of cases, the disease presents as a primary pulmonary disease with or without extrapulmonary involvement . We present a case of cutaneous blastomycosis with no evidence of pulmonary or other systemic involvement . With such presentations, the disease is presumed to have spread hematogenously with the asymptomatic or minimal primary pulmonary infection having resolved spontaneously . The patient's diagnosis was made with positive cultures and histologic examinations revealing features that are quite characteristic of blastomycosis . The patient responded to treatment with itraconazole for 6 months with no recurrence after 1 year . A high index of suspicion must be maintained when evaluating patients with progressive ulcerating or verrucous lesions that do not respond to traditional antibiotic therapy, especially with a history of recent activities in the endemic regions.

J Int Assoc Physicians AIDS Care (Chic Ill), 2002 Spring, 1(2), 53 - 62
Diagnosis and management of infectious esophagitis associated with human immunodeficiency virus infection; Zaidi SA et al.; Esophageal disease is a common complication and cause of morbidity in patients with human immunodeficiency virus (HIV) infection . Opportunistic infections are the leading cause of esophageal complaints and may be a predictor of poor long-term prognosis, presumably as a reflection of severe underlying HIV immunodeficiency . The esophagus may be the site of the first acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness in a large number of patients . Barium esophagography and upper gastrointestinal endoscopy are diagnostic modalities, commonly used to evaluate esophageal complaints in patients with AIDS . Treatment for most etiologies of esophagitis generally has a high degree of success, with a resultant improvement in quality of life . In addition to optimizing antiretroviral therapy, a thorough diagnostic assessment of every HIV-infected patient with esophageal complaints is warranted, followed by timely and appropriate treatment.

Curr Treat Options Oncol, 2003 Oct, 4(5), 421 - 30
Gastrointestinal lymphoma; Bierman PJ; The ability to make treatment recommendations for patients with gastrointestinal lymphoma is hampered by a lack of prospective trials and by a lack of uniformity in classification and staging . Patients with gastric diffuse large B-cell lymphoma have traditionally been treated with surgery and many physicians continue to recommend this approach . However, recent data suggest that these patients can be treated with combination chemotherapy regimens in the same manner as patients with nodal presentations of diffuse large B-cell lymphoma . There is evidence to suggest that adjuvant radiotherapy may improve the outcome for these patients . The recognition that extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue is a distinct clinicopathologic entity and the elucidation of the pathogenic role of Helicobacter pylori has revolutionized the treatment of these gastric lymphomas . Patients with localized disease should be managed with antibiotic therapy initially . Radiation therapy is extremely effective for these patients, but it should probably be reserved for patients who fail anti-H . pylori treatment.

J Eur Acad Dermatol Venereol, 2003 Sep, 17(5), 594 - 5
Cutaneous angiosarcoma of the face; Cannavo SP et al.; Cutaneous angiosarcoma is a rare tumour of vascular origin, which has a poor prognosis because of its high potential for metastasis . We report the case of a 57-year-old man with an 8-month history of a progressively enlarging, asymptomatic red patch over the left periorbital region of the face, previously diagnosed as angiolupoid leishmaniasis, insect-bites, 'cellulitis' and treated with several topical antibiotic and steroid therapy, without any improvement . A skin biopsy of the lesion was performed and histological and immunohistochemical examination revealed a pattern of poorly differentiated angiosarcoma . The peculiarity of the localization at the periorbital area and the particular clinical presentation are emphasized.

South Med J, 2003 Jul, 96(7), 711 - 5
Musical hallucinations in patients with Lyme disease; Stricker RB et al.; Musical hallucinations are poorly understood auditory hallucinations that occur in patients with otologic or neurologic diseases . We report the first cases of musical hallucinations in two patients with neurologic Lyme disease . Both subjects were women with clinical and laboratory evidence of chronic Lyme disease, progressive neurologic dysfunction, and abnormal magnetic resonance imaging of the brain . There was no evidence of hearing loss in either case . Musical hallucinations had a sudden onset and took the form of patriotic or operatic music . The auditory hallucinations disappeared with intravenous (i.v.) antibiotic therapy in both patients, but the hallucinations recurred when i.v . antibiotic therapy was discontinued in one case . Response to therapy was accompanied by an increase in the CD57 lymphocyte subset in one patient, whereas recurrent hallucinations were associated with persistently low CD57 levels in the other case . We conclude that musical hallucinations may be associated with neurologic Lyme disease . These auditory hallucinations appear to respond to i.v . antibiotic therapy . Patients with musical hallucinations of unknown cause should be tested for infection with the Lyme disease spirochete.

South Med J, 2003 Jul, 96(7), 685 - 8
Atypical Pott's disease: localized infection of the thoracic spine due to Mycobacterium avium-intracellulare in a patient without human immunodeficiency virus infection; Mehta JB et al.; Mycobacterium avium-intracellulare (MAI) rarely causes disease of the spine in healthy individuals . We describe an elderly woman who had isolated skeletal involvement with MAI, mimicking Pott's disease . She responded well to surgical excision of the inflamed tissue and antibiotic therapy . Osteomyelitis due to MAI must be differentiated from that due to Mycobacterium tuberculosis because the treatment regimens are different.

J Vet Med Sci, 2003 Jul, 65(7), 775 - 80
The effects of lincomycin-spectinomycin and sulfamethoxazole-trimethoprim on hyaluronidase activities and sperm characteristics of rams; Tanyildizi S et al.; The effects of lincomycin-spectinomycin and sulfamethoxazole-trimethoprim combinations on the hyaluronidase enzyme of serum and semen and on sperm characteristics in rams were determined . Thirthy-two Akkaraman rams were used . The rams were randomly divided into four groups . Group A and group B were determined as control groups of group C (lincomycin-spectinomycin) and D (sulfamethoxazole-trimethoprim), respectively . Combinations of lincomycin-spectinomycin and sulfamethoxazole-trimethoprim were administered at doses of 15 mg.kg(-1) intramuscularly and 12 mg.kg(-1) body weights orally, respectively . Blood and semen samples were collected at 4, 12, 24, 48, 72, 192 and 384 hr . Semen hyaluronidase activities of rams in group C increased significantly (p<0.001, <0.05) compared with the control group at 24 and 48 hr, respectively . Semen hyaluronidase activities in group D rams also increased significantly (p<0.001) in comparison with the control group at all times except 72 and 384 hr . Serum hyaluronidase activities increased significantly (p<0.01, <0.001) at 24 and 48 hr after treatment of lincomycin-spectinomycin . Additionally, significant (p<0.05, <0.001) increases were detected in the serum hyaluronidase activities of group D at 48 and 72 hr, respectively . No significant correlation was found between serum and semen hyaluronidase activities . Furthermore, significant increases (p<0.05) were observed in the percentages of motile sperm in the rams of group C and D compared with the control groups . The values of sperm concentration and total number of sperm in group C and D rams decreased significantly (p<0.001) in comparison with control groups . No significant correlations were found between the semen hyaluronidase activities and sperm characteristics . In conclusion, these findings show that the combinations of lincomycin-spectinomycin and sulfamethoxazole-trimethoprim do not have any harmful effects on hyaluronidase activities and sperm motility . However, the use of both antibiotic combinations in breeding rams during the ramming season is not advisable due to the decrease of sperm concentration.

J Dairy Sci, 2003 Aug, 86(8), 2622 - 8
Liquid egg as an alternative protein source in calf milk replacers; Touchette KJ et al.; The use of alternative proteins in milk replacer has been evaluated for their ability to decrease the cost of milk replacers without negatively impacting performance of the calf . Three studies were conducted to evaluate the performance of calves fed milk replacer utilizing liquid egg as an alternative protein and to determine the optimal concentration of liquid egg to include in milk replacers . Calves in trials 1 and 2 were assigned to a control diet of all milk protein replacer (MILK) or a diet formulated to contain 5% of the diet (13.5% of the protein) from liquid egg (5% EGG) . Calves in trial 3 were assigned to one of four diets: the control (MILK) and 5% EGG diets fed in trials 1 and 2, or diets formulated to contain either 10 or 15% of the diet (27 or 40.5% of the protein) from liquid egg (10% EGG, 15% EGG) . For all experiments, milk replacers were formulated to contain 20% protein, 20% fat and were fed at 454 g/d reconstituted to 12% DM . Production of the diets containing egg protein utilized breaker eggs that were pasteurized during manufacturing . Holstein bull calves (n = 44 for experiment 1, n = 38 for experiment 2, and n = 120 for experiment 3), were purchased from an area sale barn . Calves were housed in individual hutches with water available free choice starting on d 0 . A commercially available calf starter was offered free choice beginning on d 7 for experiments 1 and 2 and on d 1 for experiment 3 . Feed intake, scour scores, and antibiotic treatments were recorded daily . For experiment 1, calves fed 5% EGG had greater weight gains than calves fed MILK . No differences in average daily feed intake were observed . For experiment 2, weight gains tended to be lower with 5% EGG, whereas feed intakes and gain to feed ratios were similar between calves fed MILK or 5% EGG . For experiment 3, as the amount of egg in the diet increased, weight gain decreased in a linear fashion during the milk replacer feeding period, but the decrease in gain was significant only with the 15% EGG diet . These results indicate that egg is an effective alternative protein source to milk protein in calf milk replacers when fed at levels up to 10% of the diet in a conventional feeding program of 0.45 kg per head per day.

Chir Ital, 2003 Jul-Aug, 55(4), 519 - 24
{Acute mediastinitis: clinical features and review of a case load}; Ragusa M et al.; The term acute mediastinitis describes a number of clinical conditions, usually secondary to diseases of other aetiology with which they tend to share the severity of the clinical picture . In these situations even a timely diagnosis and adequate therapeutic management are not always enough to ensure healing . Over the period 1987-2002 15 patients with acute mediastinitis were observed (8 male, 7 female), aged from 22 to 90 years (mean age: 57.9), distributed as follows: descending necrotising mediastinitis, 4 cases; iatrogenic oesophageal rupture, 2 cases; iatrogenic tracheal rupture, 3 cases; oesophageal perforation (foreign body), 4 cases; Boerhaave's syndrome, 1 case; oesophageal perforation (lye ingestion), 1 case . All patients except one--managed medically--were submitted to mediastinal drainage (surgical or by mediastinoscopy), combined with cervical debridement and drainage in cases of descending necrotising mediastinitis, alimentary tract diversion (cervical oesophagostomy + feeding jejunostomy + gastric decompression) in cases of large oesophageal lesions or if the lesion occurred more than 24 hours before observation, and uni- or bilateral tube thoracostomy . Furthermore, antibiotic therapy was always administered, initially choosing broad-spectrum medications, and subsequently adjusting according to bacterial cultures . Four patients died . In 4 cases (2 descending necrotising mediastinitis, 2 acute mediastinitis secondary to oesophageal perforation) repeated interventions were necessary in order to drain pleural or mediastinal effusions . Acute mediastinitis remains a serious clinical entity, the outlook of which is often poor . Factors influencing outcome are the patient's age and general condition (adequate immune response), a timely diagnosis, preoperative localisation of effusions, an aggressive therapeutic approach including drainage of infection sites in the mediastinum, neck and/or pleural cavities, alimentary tract diversion in cases of oesophageal lesions observed late, adequate antibiotic therapy, and nutritional support (total parenteral/enteral nutrition).

Guang Pu Xue Yu Guang Pu Fen Xi, 2002 Oct, 22(5), 745 - 8
{In situ thin layer chromatography-fourier transform-surface-enhanced Raman spectrum study on ingredients of berberine}; Wang Y et al.; Surface Enhanced Raman Scattering (SERS) combined with Thin Layer Chromatography (TLC) has been used for studying characteristic spectrum of molecules in situ in micrograms samples . There are very few report for applying the SERS-TCL method in the study of the effective ingredients of Chinese traditional herbs . Coptis Chinensis France is an often-used clinic Chinese traditional medicine . Its main effective components include berberine and so on, which have antibiotic very wide and also have curative effect on improving the functions of heart vascular cycles . Therefore the concentrations of berberine are very important for the quality control of the medicine . In this work, the ethanol extract of Coptis Chinensis France was first separated by TLC, the SERS was then measure directly after dropping silver gel on the separated spots . The method can be used for the finger print analysis of the berberine . 3 microL of alcohol extract of Coptis Chinensis France with total alkaloids concentration of 1.0 mg.mL was placed on silicon GF254 TLC plate . The sample was separated by developing solvent of n bulanol-Acitic acid-H2O (7:2:1 V/V) . The positions of berberine in the sample were confirmed by the standard alkaloid solutions . The Rf values for berberine are 0.29 . The silver gel was used as surface enhanced substrate and placed on the separated berberine spots . FT-SERS was measured directly by a Nicolet FT-Raman 910 spectrometer . Berberine belong to isoquinoline alkaloids . His structure can be found in reference . The date of spectrum of berberine can be seen that the band at 1,396 cm-1 due to Ar-OCH3 deformation vibrations was greatly enhanced, indicating that the molecule was absorbed on silver gel strongly through lone-pair electron in Ar-OCH3 . The ring stretching mode occurring around 1,548 cm-1 represents isoquinoline ring in the molecule . The band at 727 cm-1 due to CH (ring) deformation vibrations was also enhanced.

Rev Neurol, 2003 Aug 1-15, 37(3), 221 - 4
{Aseptic meningitis caused by the rupture of an epidermoid cyst}; Pampliega-Perez A et al.; INTRODUCTION: Epidermoid cysts are rare tumours . The aseptic meningitis that comes about as a result of their rupture is frequent after tumour resection, although they may occasionally occur spontaneously . CASE REPORT: A 36-year-old male who had been submitted to surgery twice because of an epidermoid cyst in the cerebellopontine angle presented a month old history of clinical features consisting in high temperature, headache, a stiff neck and ataxia . After computerized tomography (CT) scans and a spinal tap had been performed because of the suspicion of meningitis, empirical antibiotic therapy was administered but no improvement was observed . Thus, the usual studies employed to diagnose aseptic meningitis were carried out . Magnetic resonance imaging (MRI) was performed and showed lesions that suggested tumorous recurrence and perilesional meningeal hyperenhancement . Corticoid therapy quickly lessened the symptoms and the patient was asymptomatic when discharged . A week later he returned with headaches and disorders affecting behaviour and memory . A CT scan was performed and revealed the presence of tetraventricular hydrocephalus, which required the introduction of ventriculoperitoneal drainage . Spinal MRI carried out two weeks later revealed perimedullar foci of hyperenhancement . CONCLUSIONS: We describe the case of a patient with aseptic meningitis brought on by the rupture of an epidermoid cyst, which followed a subacute course and responded to corticoid therapy in a spectacular manner . Nevertheless, the patient still went on to develop tetraventricular hydrocephalus . Spontaneous aseptic meningitis is rare and corticoids lower its development time, but hydrocephalus may occur as a complication due to upsets in the reabsorption of cerebrospinal fluid.

Parasitol Res, 2003 Jun, 90 Suppl 2, S71 - 6 Epub 2002 Nov 30.
Fosmidomycin for the treatment of malaria; Wiesner J et al.; In malaria parasites, isoprenoids are synthesised by the mevalonate independent 1-deoxy- D-xylulose 5-phosphate (DOXP) pathway . Fosmidomycin, a natural antibiotic originally developed for the treatment of bacterial infections, represents an inhibitor of DOXP reductoisomerase, an essential enzyme of this pathway . In recent clinical studies it was shown that fosmidomycin is effective in curing uncomplicated Plasmodium falciparum malaria in humans . The treatment was well tolerated and resulted in a fast parasite and fever clearance . However, the high rate of recrudescence precludes the use of fosmidomycin as a monotherapy . In drug combination studies, synergy of fosmidomycin with clindamycin was observed . Clinical studies with a fosmidomycin-clindamycin combination are currently ongoing.

Appl Microbiol Biotechnol, 2004 Mar, 64(1), 46 - 52 Epub 2003 Aug 23.
An Escherichia coli biosensor capable of detecting both genotoxic and oxidative damage; Mitchell RJ et al.; A two-plasmid dual reporter Escherichia coli biosensor was developed using the genes for bacterial bioluminescence and a mutant of the green fluorescent protein, GFPuv4 . To achieve this, the two plasmids, which were derivatives of pBR322 and pACYC184, had compatible origins of replication and different antibiotic selection markers: ampicillin and tetracycline . The parent strains DK1 and ACRG43, each carrying a single plasmid with one of the fusion genes (strain DK1 harboring a fusion of the katG promoter to the lux operon while in ACRG43, the recA promoter was fused with the GFP gene), were responsive to oxidative and DNA damage, respectively, resulting in higher bioluminescence or fluorescence under the relevant toxic conditions . The responses of the dual sensor strain, DUAL22, to various toxicants, e.g., mitomycin C, N-methyl-N-nitro--nitrosoguanidine, hydrogen peroxide and cadmium chloride, were characterized and compared with the responses of the parent strains to the same chemicals . Finally, several chemical mixtures that cause various stress responses were tested to demonstrate the ability of this biosensor to detect specific stress responses within a multiple toxicity environment.

Antimicrob Agents Chemother, 2003 Sep, 47(9), 2892 - 6
Resistance to the peptidyl transferase inhibitor tiamulin caused by mutation of ribosomal protein l3; Bosling J et al.; The antibiotic tiamulin targets the 50S subunit of the bacterial ribosome and interacts at the peptidyl transferase center . Tiamulin-resistant Escherichia coli mutants were isolated in order to elucidate mechanisms of resistance to the drug . No mutations in the rRNA were selected as resistance determinants using a strain expressing only a plasmid-encoded rRNA operon . Selection in a strain with all seven chromosomal rRNA operons yielded a mutant with an A445G mutation in the gene coding for ribosomal protein L3, resulting in an Asn149Asp alteration . Complementation experiments and sequencing of transductants demonstrate that the mutation is responsible for the resistance phenotype . Chemical footprinting experiments show a reduced binding of tiamulin to mutant ribosomes . It is inferred that the L3 mutation, which points into the peptidyl transferase cleft, causes tiamulin resistance by alteration of the drug-binding site . This is the first report of a mechanism of resistance to tiamulin unveiled in molecular detail.

Leg Med (Tokyo), 2001 Dec, 3(4), 246 - 51
Fatal Aspergillus pancarditis after incompatible blood transfusion intended to be an autologous blood transfusion; Ohya I et al.; Aspergillus pancarditis is a rare infection, and it has rarely been reported after blood transfusion . In this report, we describe a fatal case of Aspergillus pancarditis in a patient who received antibiotics and corticoids after an incompatible blood transfusion intended to be an autologous blood transfusion . A 64-year-old man suffering from herniation of intervertebral disk between C4 and C5 received an anterior cervical spinal fusion . After the operation, he received incompatible blood transfusion and fell into disseminated intravascular coagulation (DIC) and preshock state . Anticoagulants and corticoids were given and he recovered from DIC and the preshock state . However, he remained quadriplegic because of enlargement of cervical epidural hematoma that was initially brought out by the operation . He developed bacterial bronchopneumonia 2 weeks after the transfusion and received antibiotic therapy . The pneumonia was cured a week later . Five weeks after the transfusion, he developed Aspergillus pneumonia and received antimycotic therapy . However, his condition grew worse and died 2 months after the transfusion . Autopsy revealed Aspergillus pancarditis . In this case, the relationship between the erroneous transfusion and the patient's death was obvious and it was considered that the erroneous transfusion should be blamed for the patient's death.

Rev Fac Cien Med Univ Nac Cordoba, 2001, 58(1), 65 - 76
{Identification of Helicobacter pylori and associated gastric lesions}; Cejas HA et al.; In this study is presented a silver stain technique for Helicobacter pylori with ammoniacal silver carbonato of Del Rio Hortega, in biopsies and surgical specimens embebbed in paraffine . This study was performed between 1999 to 2001, and 717 gastroscopics biopsies were observed, that included: 705 chronic gastritis (98.32%), 11 gastric carcinomas (1.53%), and 1 low-grade lymphoma (0.13%) . It is important to note the low incidence of adenocarcinomas and lymphomas from 717 gastroscopic biopsies during the period of 1999-2001, only 11 carcinomas and 1 lymphoma . We added 28 retrospective studies of biopsies and surgical specimens . These latter group included 21 adenocarcinomas and 7 low-grade lymphomas . Hence, there were a total of 745 cases with: 705 chronic gastritis, 32 adenocarcinomas, and 8 low-grade lymphomas . In 705 chronic gastritis, 325 (46.10%) were associated with H pylori, and they were Chronic Superficial Gastritis of Mild (8.62%), Moderate (61.23%), and Severe (12.92%) intensity; and Follicular Gastritis in 17.23% . In a serie of 82 total Follicular Gastritis (82/705), H pylori was founded in 68.29% (56/82) . This relative frequency of association between H pylori with Chronic Gastritis in general (46.10%), and with Follicular Gastritis in particular (68.29%), could be explain because: a--many gastroscopic biopsies did not became from antrum, site of H pylori growing . Or b--there was another etiologic factor without morphologic value . There is a clear evidence that H pylori is an important factor in the pathogenesis of these chronic gastritis, from primary Acute Gastritis occurred in children and young patients, to Chronic Superficial Gastritis, Follicular Gastritis, Atrophic Gastritis, intestinal metaplasia, and Peptic Ulcer present in adult patients . Adenocarcinomas were associated with moderate and severe Chronic Superficial Gastritis, Atrophic Gastritis, intestinal metaplasia, and moderate and severe dysplasias of glandular epithelium . H pylori was founded in only 35% of adenocarcinomas, probably related to the presence of atrophic gastritis associated with metaplastic/dysplastic changes, or necrotic tissues, which would possibly explain the absent of H pylori growing under these circumstances . Low-grade lymphomas (MALT-type), arise from lymphatic tissue of the mucosa, and were associated with chronic gastritis, atrophy, and intestinal metaplasia . H pylori was founded in 75% of all lymphomas . Also in this case, there is a clear pathogenic evidence between H pylori infection and the development of low-grade lymphoma, specially in early stages, since it is possible the complete resolution after antibiotic therapy or partial gastrectomy.

Eur J Obstet Gynecol Reprod Biol, 2003 Sep 10, 110(1), 49 - 54
New evidence of the influence of exogenous and endogenous factors on sperm count in man; Wong WY et al.; OBJECTIVE: To examine the association between individual exposures due to occupation, environment and lifestyle on sperm count, we conducted a case-control study among 92 fertile and 73 sub-fertile Caucasian males . STUDY DESIGN: Data from questionnaires were analysed using simple univariate and multivariate logistic regression models . RESULTS: At risk for oligozoospermia are men exposed to pesticides (odds ratio (OR) 8.4; 95% confidence interval (CI) 1.3-52.1), welding (OR 2.8; CI 0.9-8.7), antibiotic use (OR 15.4; CI 1.4-163), a history of mumps (OR 2.9; CI 1.3-6.7), gastrointestinal complaints (OR 6.2; CI 1.4-26.8), decreased intake of fruits (OR 2.3; CI 1.0-5.1), vegetables (OR 1.9; CI 0.7-5.0), or with female fertility disorders in their families (OR 8.4; CI 1.7-41.9) . Unlike other studies, no associations were observed between oligozoospermia and exposure to paint or heat . CONCLUSION: This study suggests new risk factors oligozoospermia in man and confirms previously reported results from others.

Kyobu Geka, 2003 Aug, 56(9), 761 - 4
{Management of mediastinitis after pediatric cardiac surgery with continuous closed irrigation method}; Matsubara M et al.; Two cases are presented as a successful management for mediastinitis with the continuous closed irrigation method after pediatric cardiac surgery . The continuous closed irrigation method has significant advantages over conventional open irrigation method or muscle flap in pediatric cases, because the system is simple to handle and easy to wash out any infectious tissue debris without additional invasive intervention . However, adequate duration of the irrigation and subsequent antibiotic regimen is still unclear . We conclude that the continuous closed irrigation method is an effective management which is applicable to most of mediastinitis cases after pediatric cardiac surgery.

Rozhl Chir, 2003 May, 82(5), 245 - 9
{Continuous lavage in the treatment of severe necrotizing pancreatitis}; Bober J et al.; OBJECTIVE: The objective was to summarize five-year experience with the method of closed continuous lavage in the treatment of severe necrotic pancreatitis . To compare the advantages and disadvantages and to compare the achieved results with those of other authors . METHOD: The authors evaluated in the form of a retrospective analysis the results achieved in a group of 54 patients treated by the above method implemented under conditions and rules defined in advance . The drains were placed with regard to the results of CT and the surgical finding . For the lavage saline was used with addition of antibiotic alternately with Povidon iodide solution . Parameters and objectives outlined in advance were followed up . RESULTS: As the main criteria of evaluation and comparison of results was evaluation of the mortality (27.7%) in the whole group of the most severe forms of acute pancreatitis . It is comparable with the world literature . The incidence of complications and relatively small number of surgical revisions (33%), the mean period of hospitalization (56.8 days) and tolerance of the procedure by the patients were also evaluated positively . CONCLUSIONS: The method of continuous closed lavage in the treatment of severe forms of acute pancreatitis is an asset to the contemporary therapeutic concept due to the high predominance of advantages over disadvantages.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003 Aug, 96(2), 207 - 14
Comparison of preoperative pain and medication use in emergency patients presenting with irreversible pulpitis or teeth with necrotic pulps; Nusstein JM et al.; OBJECTIVE: This retrospective study compared differences in preoperative pain and medication use in patients with moderate to severe pain who sought emergency endodontic care for teeth with irreversible pulpitis and for symptomatic teeth with necrotic pulps . STUDY DESIGN: A total of 323 patients seeking emergency endodontic treatment completed questionnaires regarding their biographical information, pain, pain history, and medications . Teeth were tested for vitality, mobility, percussion, and palpation pain . Lymphadenopathy was also evaluated . RESULTS: Patients with irreversible pulpitis waited significantly (P <.05) longer before seeking emergency care (9 days vs 4 days) than patients with symptomatic teeth with necrotic pulps . No differences (P >.05) were found between the groups in terms of analgesic or antibiotic use and pain relief from preoperative narcotic medications . Nonnarcotic analgesics were reported to significantly reduce pain more often in patients with symptomatic teeth with necrotic pulps . There were sex differences in the group of patients with irreversible pulpitis: More women than men were taking analgesic medications and, in the group having symptomatic teeth with necrotic pulps, more men than women reported pain relief from their analgesic medications . CONCLUSION: Patients with irreversible pulpitis wait longer to seek emergency treatment . A majority (81%-83%) of emergency patients with moderate to severe pain will have taken some type of medication(s) to help control their pain, and more women than men with irreversible pulpitis will take an analgesic . By taking their preoperative medication(s), this group of patients will get relief 62% to 65% of the time; furthermore, more men than women with symptomatic teeth with necrotic pulps will experience pain relief.

J Med Assoc Thai, 2003 Jun, 86 Suppl 2, S439 - 44
Pattern of drug resistant Helicobacter pylori in dyspeptic patients in Thailand; Tangmankongworakoon N et al.; Emergence of drug resistant Helicobacter pylori (H . pylori) has occurred in various countries and could compromise the efficacy of current treatment regimens . The aim of the study was to identify the pattern of antibiotic resistant H . pylori in Thailand and evaluate various factors associated with drug resistance . Between June 2001 and December 2002, a total of 560 dyspeptic patients who underwent upper gastrointestinal endoscopy at King Chulalongkorn Memorial Hospital were included in this study . Antral gastric biopsies were obtained for H . pylori cultures and susceptibility tests using Epsilometer test (E-test) . The value of antibiotic resistant breakpoints were amoxicillin 0.5 microg/ml, clarithromycin 1.0 microg/ml, metronidazole 8 microg/ml, and tetracycline 4 microg/ml, respectively . H . pylori were detected in 315 patients using the rapid urease test (56.25%) . Cultures for H . pylori were positive in 172 patients . E-test for all four antibiotics was successfully placed in 79 isolations . The prevalence of antibiotic resistant H . pylori were amoxicillin 13.9 per cent (11/79), clarithromycin 19.0 per cent (15/79), metronidazole 30.4 per cent (24/79), tetracycline 5.1 per cent (4/79), and multi-drugs 16.5 per cent (13/79), respectively . However, age, sex, or endoscopic findings did not differ between the patients with H . pylori resistant strains and sensitive strains . The emergence of antibiotic and multi-drug resistant H . pylori in Thailand were relatively high and these could compromise the efficacy of current treatment regimens . The factors associated with drug resistant H . pylori could not be demonstrated in the present study . Further study in a larger number of patients might be necessary to identify factors associated with resistant H . pylori.

Org Biomol Chem, 2003 Feb 21, 1(4), 684 - 91
The use of enantiomerically pure ketene dithioacetal bis(sulfoxides) in highly diastereoselective intramolecular nitrone cycloadditions . Application in the total synthesis of the beta-amino acid (-)-cispentacin and the first asymmetric synthesis of cis-(3R,4R)-4-amino-pyrrolidine-3-carboxylic acid; Aggarwal VK et al.; Intramolecular 1,3-dipolar nitrone cycloaddition onto an enantiomerically pure ketene dithioacetal dioxide using a three-carbon tether gave the corresponding 5,5-disubstituted isoxazolidine as a single diastereomer in good yield . This reaction has been used as the key step in an asymmetric synthesis of the naturally occurring antibiotic, (-)-cispentacin . An asymmetric synthesis of 4-amino-pyrrolidine-3-carboxylic acid has also been carried out using the intramolecular nitrone cycloaddition as the stereocontrolling step.

Nurs Stand, 2003 Jul 23-29, 17(45), 47 - 53; quiz 54, 56
MRSA: an infection control overview; Rayner D; MRSA is challenging nursing and medical professionals in hospitals and the community . Effective antibiotic therapy and risk assessment are needed together with good infection control practice to reduce its transmission.

Eur J Echocardiogr, 2003 Sep, 4(3), 221 - 2
Transoesophageal echocardiographic diagnosis of aortico-left atrial fistula in aortic valve endocarditis; Esen AM et al.; Intra-cardiac fistulas are rarely seen and they are estimated to account for <1% of all cases of infective endocarditis . Fistulization of paravalvular abscesses has been found in 6% to 9% of cases . This is a report of an unusual communication between the abscess region in the aortic root and the left atrium . A 44-year-old patient diagnosed with infective endocarditis had continuous fevers despite antibiotic therapy . Transoesophageal echocardiography revealed multiple vegetations on aortic valve, fistulization of an aortic root abscess to the left atrium and mitral regurgitation and moderate aortic regurgitation . At surgery, multiple vegetations on the aortic valve and a large abscess cavity establishing direct communication between aortic root and the left atrial cavity through a fistulous tract were discovered . This experience demonstrates the improved sensitivity and specificity of transoesophageal echocardiography in defining periannular extension of infective endocarditis.

J Clin Virol, 2003 Sep, 28(1), 44 - 50
Rotaviral and bacterial gastroenteritis in children during winter: an evaluation of physician ordering patterns; Chemaly RF et al.; BACKGROUND: Identification of the agents of infectious diarrhea may facilitate appropriate therapy and prevent inappropriate antibiotic use . OBJECTIVES: To better define the etiology of infectious diarrhea for children <12 years in our community and to study the ordering patterns of physicians . STUDY DESIGN: We reviewed test results of stool specimens from children <12 years old at our institution (CCF) and those submitted through our reference laboratory for rotavirus enzyme immunoassay (REIA) and stool cultures for a 7-month period (11/1/00-6/1/01) . For CCF patients, REIA and stool cultures for usual bacterial enteric pathogens (BEP) were performed, regardless of the test ordered (i.e . REIA alone, stool culture alone or both) . We compared the results with the orders placed to determine if requests for rotavirus alone or bacterial stool culture alone missed BEP or rotavirus, respectively . RESULTS: Overall, REIAs were performed on 81% (538/661) of stool specimens, with 37% positive . Stool cultures were performed on 62% (408/661) of stool specimens, with 4.4% positive . Stool specimens (280) from CCF pediatric patients were evaluated for both rotavirus and BEP . Some 42% of REIA and 23% of stool cultures were ordered as single tests, while both tests were ordered for 35% of the patients . Of the REIA ordered alone, 34% were positive for rotavirus; however, 2.5% of these contained BEP that would have been missed . Of the stool cultures that were ordered alone, 8% were positive; however, 19% of these contained rotavirus that would have been missed . When both tests were ordered, 22% contained rotavirus and 2% contained BEP . CONCLUSION: Both rotavirus and bacterial enteric infections were missed with selective viral versus bacterial specific ordering patterns . A rotaviral screen prior to stool culture may be useful for children with diarrhea during the winter months.

Auris Nasus Larynx, 2003 Aug, 30(3), 279 - 82
A rare and serious complication of chronic otitis media: lateral sinus thrombosis; Unsal EE et al.; Before the antibiotic era, lateral sinus thrombosis (LST) was the most frequent complication of otitis media . With the widespread usage of antibiotics, its occurrence is rare . Nevertheless, it is still a major complication of middle ear disease . LST mortality fluctuates between 5 and 35% . The major clinical symptoms of patients with LST are pain in the mastoid region, spiking fever, anemia and general health disorders . Computed tomography, magnetic resonance imaging and angiography are the most helpful in diagnosis, but the final diagnosis is made by surgical exploration . Three cases with LST are presented, and signs, diagnosis and treatment of disease are discussed.

Org Biomol Chem, 2003 May 21, 1(10), 1690 - 700
Synthesis of 3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl pyranonaphthoquinone analogues of medermycin; Brimble MA et al.; The synthesis of an isomeric mixture of 4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl analogues 6 of the C-glycosylpyranonaphthoquinone antibiotic medermycin is described . The key 3-acetyl-6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-5-methoxy-1,4-naphthoquinone 8 was prepared via Stille coupling of 6-(3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)-3-bromo-1,4- naphthoquinone 17 with (alpha-ethoxyvinyl)tributyl-stannane followed by hydrolysis and oxidation of the resultant hydroquinone 18 . Bromonaphthoquinone 17 in turn was afforded by oxidative demethylation of 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)-3- bromo-1,4,5-trimethoxynaphthalene 16 formed by regioselective bromination of 6-(4-acetyl-3-azido-2,3,6-trideoxy- beta-D-arabino-hexopyranosyl)-1,4,5-trimethoxynaphthalene 10 . This latter naphthalene 10 was prepared via direct C-glycosylation of naphthol 12 with glycosyl donor 11 using BF3.Et2O in acetonitrile . The regioselectivity of the bromination of naphthalene 10 was independently determined by reductive monomethylation of the 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-5-methoxy-1,4-naphthoquinone 22 to naphthol 23 followed by selective ortho bromination to bromide 24 and methylation to 16 . Attempts to effect acetylation of 6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-3-bromo-1,4,5-trimethoxynaphthalene 16 and 3-bromo-6-(3-dimethylamino-2,3,6-trideoxy-beta-D-arabino- hexopyranosyl)-1,4,5-trimethoxynaphthalene 26 via Stille coupling with (alpha-ethoxyvinyl)tributylstannane were low yielding thereby establishing the necessity to use an azido group as a latent dimethylamino group and a more electrophilic bromonaphthoquinone as the coupling partner for the Stille reaction . Addition of 2-trimethylsilyloxyfuran 9 to 3-acetyl-6-(4-O-acetyl-3-azido-2,3,6-trideoxy-beta-D-arabino-hexopyranosyl)- 5-methoxy-1,4-naphthoquinone 8 afforded the furofuran adducts 7 and 19 as an inseparable mixture of diastereomers . Oxidative rearrangement of this diastereomeric mixture using ceric ammonium nitrate afforded the inseparable diastereomeric furonaphthopyrans 6 and 20.

Asian J Surg, 2003 Jul, 26(3), 180 - 2
Suppurative thyroiditis with gas formation; Reksoprawiro S; Acute suppurative thyroiditis with gas formation is very rare . A 70-year-old woman was admitted with dysphagia and fever . The clinical diagnosis of acute thyroiditis was supported by fine needle aspiration biopsy . X-ray examination showed gas collection within the soft tissue of the anterior neck and ultrasonography of the thyroid gland showed a cavity filled with thick liquid . The patient was treated with antibiotic therapy followed by thyroidectomy.

Neurol Med Chir (Tokyo), 2003 Jul, 43(7), 360 - 3
Intraventricular rupture of Nocardia brain abscess--case report; Oshiro S et al.; A 71-year-old male presented with left hemiparesis and confused conversation . Computed tomography showed a mass lesion with rim enhancement in the right parietal lobe . He developed meningeal irritation the day after admission . Emergent fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging revealed a clear hyperintense component in the right lateral ventricle and niveau formation inside the intracerebral lesion, indicating intraventricular rupture of the brain abscess . The patient underwent aspiration of the abscess and ventricular drainage with antibiotic administration . Nocardia asteroides was isolated from the aspirated pus, so systemic and direct administration of effective antibiotics was subsequently commenced . These procedures resulted in gradual improvement of his clinical course, and he left our hospital . Several days after discharge, he developed acute pan-peritonitis due to malignant lymphoma . He appeared to be progressively deteriorating after an exploratory laparotomy, and died on the 17th day after the laparotomy . Intraventricular rupture of nocardia brain abscess can be successfully treated after early definitive diagnosis with FLAIR MR imaging.

Intern Med, 2003 Aug, 42(8), 665 - 9
Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole; Mori H et al.; OBJECTIVE: High-dose trimethoprim-sulfamethoxazole (TMP-SMX) is known to cause hyperkalemia by blocking amiloride-sensitive sodium (Na) channels in distal nephrons . The purpose of this study was to establish whether the standard dose of TMP-SMX could cause electrolyte disorders . METHODS AND PATIENTS: Serum Na, potassium (K) and creatinine (Cr) levels were examined retrospectively in 53 of 77 patients prescribed TMP-SMX, before and after taking the antibiotic combination . RESULTS: Electrolyte disorders (Na < 135 mEq/l and/or K > 5.0 mEq/l) were found in 14 of the 53 patients (26.4%) during TMP-SMX treatment . The average dose was 145.7 +/- 24.9 mg/day . The dose of TMP was significantly larger in patients with electrolyte disorders (267.7 +/- 84.2 mg vs . 101.9 +/- 9.38 mg, p = 0.0024) . Electrolyte disorders were also seen in 9.1% and 22.2% of patients given the low dose (TMP < 80 mg) or standard dose (TMP 80-120 mg) of TMP-SMX, respectively . Electrolyte disorders were seen in 85.7% of patients with renal dysfunction (Cr > 1.2 mg/dl), compared with 17.5% of patients with normal renal function (p = 0.0008) . Logistic regression analysis showed that the dose of TMP and the presence of renal dysfunction increased the incidence of electrolyte disorders with an odds ratio of 2.35 and 80.29, respectively . CONCLUSION: Electrolyte disorders, particularly hyperkalemia and hyponatremia can be detected in patients given TMP-SMX . These disorders are more frequent in patients given high doses, but can also be detected after low-dose administration . Renal dysfunction accelerates the incidence of electrolyte disorders induced by TMP-SMX.

Ukr Biokhim Zh, 2002 Nov-Dec, 74(6), 103 - 7
{Study of the binding between bacterial lipopolysaccharides and polymyxin by a bioluminescent method}; Katsev AM et al.; For rating the interaction of lipopolysaccharides (LPS) with polymixin B (PmB) a bacterial bioluminescence is offered to be used . Bioluminescence level of bacteria decreases under free antibiotic amounts action . It is shown, that as a result of interaction with LPS antibiotic properties of PmB are reduced, and the intensity of bacterial bioluminescence is restored . The bioluminescence level in such system characterizes the LPS quantity . Kinetic properties of bacterial light emission at the presence of LPS and PmB are investigated as well as equilibrium state of the system . Kinetic and equilibrium constants describing this reaction are determined . The conditions of quantitative bioluminescent definition of LPS in an interval of concentration 0.166-10 micrograms/ml have been chosen and calibration curves are presented.

Theor Appl Genet, 2003 Nov, 107(8), 1410 - 8 Epub 2003 Aug 15.
A cytoplasmically inherited mutant controlling early chloroplast development in barley seedlings; Prina AR et al.; Cytoplasmic line 2 (CL2) has been previously reported as a cytoplasmically inherited chlorophyll-deficient mutant selected from a chloroplast-mutator genotype of barley . It was characterized by a localized effect on the upper part of the first-leaf blade . At emergence the CL2 seedlings-phenotype varied from a grainy light green to an albino color . They gradually greened during the following days, starting from the base of the blade and extending to cover most of its surface when it was fully grown . The present results, from both light microscopy and transmission electron microscopy (TEM), confirmed the previously described positional and time-dependent expression of the CL2 syndrome along the first-leaf blade . During the first days after emergence, light microscopy showed a normally developed chloroplast at the middle part of the CL2 first-leaf blade, meanwhile at the tip only small plastids were observed . TEM showed that the shapes and the internal structure of the small plastids were abnormal, presenting features of proplastids, amyloplasts and/or senescent gerontoplasts . Besides, they lack plastid ribosomes, contrasting with what was observed inside chloroplasts from normal tips, which presented abundant ribosomes . Phenotypic observations and spectrophotometric analysis of seedlings produced by mother plants that had been grown under different temperatures indicated that higher temperatures during seed formation were negatively associated with pigment content in CL2 seedlings . In contrast, higher temperatures during the growth of CL2 seedlings have been associated with increased pigment content . Aqueous solution with kanamycin and streptomycin, which are antibiotics known to interfere with plastid gene translation, were used for imbibition of wild-type and CL2 seeds . Antibiotic treatments differentially reduced the chlorophyll content in the upper part of the first-leaf blade in CL2, but not in wild-type seedlings . These results suggest that in the wild-type, plastid-gene proteins which are necessary for chloroplast development and chlorophyll synthesis in the upper part of the first-leaf blade are usually synthesized during embryogenesis . However, under certain circumstances, in CL2 seedlings, they would be synthesized after germination . In addition, a shortening of the sheath has been observed in association with pigment decrease suggesting the existence of plastid factors affecting the expression of some nuclear genes . We consider the CL2 mutant a unique experimental material useful to study biological phenomena and external factors regulating plastid, and nuclear gene expression during embryogenesis and early seedling development.

Biomol Eng, 2003 Jul, 20(4-6), 339 - 47
Long-term culture of sponge explants: conditions enhancing survival and growth, and assessment of bioactivity; de Caralt S et al.; Sponges are an important source of secondary metabolites with pharmaceutical interest . This is the main reason for the increasing interest of sponge culture recent years . The optimal culture system depends on the species to be cultured: while some species easily produce sponge aggregates after dissociation (primmorphs), others show a great capacity to regenerate after fragmentation (explants) . Corticium candelabrum is a Mediterranean bacteriosponge that can undergo asexual reproduction . We have taken advantage of this capability and cultured C . candelabrum explants under several experimental conditions . To find the best conditions for obtaining functional explants, we assayed a range of conditions, including seasons of collection, culture temperature, filtered versus filtered-sterile seawater, addition of antibiotics and proportion of ectosome . We monitored the changes in shape and ultrastructure during the formation of explants . After 24 h, TEM images showed the aquiferous system disarranged, in particular at the sponge periphery . From 2 to 4 weeks later, the aquiferous system regenerated, and fragments became functional sponges (explants) . Explants were cultured under two regimes: in vitro and in a closed aquarium system . Antibiotics were only added to the in vitro culture to assess their effect on the symbiotic bacteria, which remained healthy despite the presence of antibiotics . Two food regimens (marine bacteria and green algae) were assayed for their ability to satisfy the metabolic requirements of explants . We monitored explant survival and growth . Explants showed a high long-term survival rate (close to 100%) . Growth rates were higher in the closed aquarium system, without antibiotic addition, and fed with algae . Explants cultures were hardly contaminated because manipulation was reduced to a minimum and we used sterilized seawater . C . candelabrum produces bioactive molecules, which may play a defensive role in the sponge and may have pharmaceutical interest . The bioactivity of the explants was similar to that of wild sponges.

Cochrane Database Syst Rev . 2003;(3):CD000978.
Interventions for preventing oral mucositis for patients with cancer receiving treatment; Clarkson JE et al.; BACKGROUND: Treatment of cancer is increasingly more effective but is associated with short and long term side effects . Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them . One of these side effects is oral mucositis (mouth ulcers) . OBJECTIVES: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment . SEARCH STRATEGY: The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched . Reference lists from relevant articles were scanned and the authors of eligible studies were contacted to identify trials and obtain additional information.Date of most recent searches June 2002 . SELECTION CRITERIA: Trials were selected if they met the following criteria: design - random allocation of participants; participants - anyone with cancer receiving chemotherapy or radiotherapy treatment for cancer; interventions - agents prescribed to prevent oral mucositis; outcomes - prevention of mucositis, pain, amount of analgesia, dysphagia, systemic infection, length of hospitalisation, cost and patient quality of life . DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions and outcome measures and results were independently extracted, in duplicate, by two reviewers . Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out . The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using random effects models . MAIN RESULTS: One hundred and nine studies were eligible . Fifty-seven were excluded for various reasons, usually as there was no useable information on mucositis . Of the 52 useable studies all had data for mucositis comprising 3594 randomised patients . Interventions evaluated were: acyclovir, allopurinol mouthrinse, amifostine, antibiotic pastille or paste, benzydamine, camomile, chlorhexidine, clarithromycin, folinic acid, glutamine, GM-CSF, hydrolytic enzymes, ice chips, oral care, pentoxifyline, povidone, prednisone, propantheline, prostaglandin, sucralfate and traumeel . Of the 21 interventions included in trials, nine showed some evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis . Interventions where there was more than one trial and a significant difference compared with a placebo or no treatment were allopurinal with unreliable evidence for a reduction in the severity of mucositis OR = 0.01 (95% CI: 0 to 0.03), amifostine provided minimal benefit in preventing mucositis RR = 0.95 (95% CI: 0.91 to 0.99), antibiotic paste or pastille demonstrated a moderate benefit in preventing mucositis RR = 0.87 (95% CI: 0.79 to 0.97), GM-CSF prevented mucositis RR = 0.51 (95% CI: 0.29 to 0.91), hydrolytic enzymes reduced the severity of mucositis RR = 0.49 (95% CI: 0.30 to 0.81), and ice chips prevented mucositis OR = 0.42 (95% CI: 0.19 to 0.93) . Other interventions showing some benefit with only one study were: benzydamine, oral care protocols and povidone.The NNT to prevent one patient experiencing mucositis over a baseline incidence of 60% for amifostine is 33 (95% CI: 20 to 100), antibiotic paste or pastille 13 (95% CI: 8 to 50), GM-CSF 3 (95% CI: 2 to 20) and ice chips 5 (95% CI: 2 to 31) . When the baseline incidence is 40%/90% the NNTs for amifostine are 50/20, for antibiotic paste or pastille 20/8, for GM-CSF 5/2 and for ice chips 6/10.The general reporting of RCTs was poor . However, the quality of the randomisation improved when the authors provided additional information . REVIEWER'S CONCLUSIONS: Several of the interventions were found to have some benefit at preventing or reducing the severity of mucositis associated with cancer treatment . The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types hat benefits may be specific for certain cancer types and treatment . There is a need for well designed and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.

Pediatr Med Chir, 2003 Mar-Apr, 25(2), 135 - 8
{CVS-cardiac thrombosis related in a child with an intracranial germinoma}; Portaleone D et al.; We report a case of a CVC infection with a grave cardiac thrombosis in a child afflicted with intracranial functioning germinoma . During the second chemotherapeutic cycle we found a positive blood culture and a partial CVC occlusion; echocardiography showed a 2 cm diameter interatrial thrombus . After removal of the CVC a voluminous thrombus in the right atrium persisted . The profibrinolytic factor's concentration was normal, and so we preferred to use aspirin, the most common antiplatelet agent, combined with antibiotic and antimycotis therapy . This treatment allowed us to observe the disappearance of the thrombus by 25 days.

J Trauma, 2003 Aug, 55(2), 263 - 7; discussion 267-8
Optimal threshold for diagnosis of ventilator-associated pneumonia using bronchoalveolar lavage; Miller PR et al.; BACKGROUND Identification of ventilator-associated pneumonia (VAP) with invasive methods such as bronchoalveolar lavage (BAL) paired with treatment is associated with improved mortality . Inappropriate antibiotic use, however, is known to increase bacterial resistance, making future treatment problematic . Thus, the diagnostic threshold for VAP in BAL must yield adequate sensitivity while limiting exposure of patients to unnecessary antibiotics . Our institution uses a cutoff of > or = 10(5) colony-forming units (CFUs)/mL, but the optimal cutoff remains an area of debate . In this project, the effects of lower diagnostic cutoffs on VAP diagnosis and unnecessary antibiotic use are examined . METHODS: Records of all patients admitted to the trauma intensive care unit over a 2-year period requiring > 48 hours of mechanical ventilation were reviewed . Number of BALs, quantity of organism on each BAL, and presence of VAP (> or = 10(5) CFUs/mL) were noted . Indication for BAL was pulmonary infiltrate, sepsis syndrome, and C-reactive protein > 17 microg/dL at > or = 48 hours after admission . RESULTS: From January 1, 2000, to December 31, 2001, 563 patients were admitted to the trauma intensive care unit . Two hundred fifty-seven required > 48 hours of mechanical ventilation, and 257 BALs were performed in 168 (65%) of these patients . One hundred thirty-nine episodes of VAP occurred in 109 (42%) patients . Subdiagnostic quantities of bacteria (> or = 10(2) but < 10(5) CFUs/mL) were seen in 98 BALs . Of these, only 16 (16%) episodes of VAP with the same organism were seen later during hospitalization . At a threshold of > or = 10(4) CFUs/mL, 4 of 28 (14%) patients went on to develop pneumonia . A similar pattern was seen at diagnostic thresholds of > or = 10(3) CFUs/mL (10 of 72 {14%}) and > or = 10(2) CFUs/mL (16 of 98 {16%}) . CONCLUSION: A threshold of > or = 10(5) CFUs/mL for VAP diagnosis carries a low false-negative rate . Over 80% of additional patients who would have been treated had a threshold of > or = 10(4) CFUs/mL been used recovered without treatment and thus would have undergone unnecessary antibiotic exposure . A similar pattern is seen at all lower thresholds . Lower diagnostic thresholds would lead to marginal increase in sensitivity, and many would receive unnecessary VAP treatment with potential for increasing bacterial resistance.

J Trauma, 2003 Aug, 55(2), 255 - 60; discussion 260-2
Clinical predictors of subtherapeutic aminoglycoside levels in trauma patients undergoing once-daily dosing; Toschlog EA et al.; BACKGROUND: After publication of the Hartford nomogram in 1995, conflicting data have emerged regarding the use of once-daily aminoglycoside (ODA) regimens in critically ill patients . The purpose of this study was to characterize a trauma patient population with low 10-hour aminoglycoside levels (THL) within the Hartford ODA protocol . METHODS: Patients admitted to a Level I trauma center who received aminoglycosides were eligible for study . Clinical and demographic data were prospectively collected . Patients were dosed according to the Hartford protocol and a THL was obtained . Patients with THL < 2.0 microg/mL (OFF cohort) were compared with those falling within the nomogram (ON cohort) . RESULTS: Of 79 patients receiving ODA therapy, 46 (58.2%) patients fell off the nomogram . The OFF cohort was associated with younger age and higher creatinine clearance, and related inversely to net resuscitative volume . CONCLUSION: Trauma patients undergoing ODA therapy with low THL are younger and exhibit less net preaminoglycoside resuscitative volume and higher creatinine clearance . These findings may have important clinical implications regarding antibiotic efficacy in these select patients.

Eukaryot Cell, 2003 Aug, 2(4), 756 - 68
Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote; Salto ML et al.; Differentiation of Trypanosoma cruzi trypomastigotes to amastigotes inside myoblasts or in vitro, at low extracellular pH, in the presence of {(3)H}palmitic acid or {(3)H}inositol revealed differential labeling of inositolphosphoceramide and phosphatidylinositol, suggesting that a remodeling process takes place in both lipids . Using (3)H-labeled inositolphosphoceramide and phosphatidylinositol as substrates, we demonstrated the association of at least five enzymatic activities with the membranes of amastigotes and trypomastigotes . These included phospholipase A(1), phospholipase A(2), inositolphosphoceramide-fatty acid hydrolase, acyltransferase, and a phospholipase C releasing either ceramide or a glycerolipid from the inositolphospholipids . These enzymes may be acting in remodeling reactions leading to the anchor of mature glycoproteins or glycoinositolphospholipids and helping in the transformation of the plasma membrane, a necessary step in the differentiation of slender trypomastigotes to round amastigotes . Synthesis of inositolphosphoceramide and particularly of glycoinositolphospholipids was inhibited by aureobasidin A, a known inhibitor of fungal inositolphosphoceramide synthases . The antibiotic impaired the differentiation of trypomastigotes at acidic pH, as indicated by an increased appearance of intermediate forms and a decreased expression of the Ssp4 glycoprotein, a characteristic marker of amastigote forms . Aureobasidin A was also toxic to differentiating trypomastigotes at acidic pH but not to trypomastigotes maintained at neutral pH . Our data suggest that inositolphosphoceramide is implicated in T . cruzi differentiation and that its metabolism could provide important targets for the development of antiparasitic therapies.

J Gastroenterol Hepatol, 2003 Sep, 18(9), 1039 - 46
Inducible nitric oxide synthase activity induced by sodium chloride solution prolongs luminal pH elevation in rat and mouse stomachs; Tatemichi M et al.; BACKGROUND: Sodium chloride (NaCl) is a strong promoter of gastric cancer . We hypothesized that inducible nitric oxide synthase (iNOS) induced by NaCl may be involved in its promoting effects . We investigated iNOS expression by hypertonic NaCl solutions and its pathophysiological roles in the gastric mucosa of rats and mice . METHODS: iNOS mRNA and protein expressions were examined in the rat and mouse gastric mucosa after intragastric administration of NaCl solution by northern blot, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry . The effect on luminal pH by iNOS activity was assessed using aminoguanidine, a potent iNOS inhibitor, and iNOS gene deficient (iNOS-/-) mice . RESULTS: iNOS expression was detected at concentrations higher than 1.7 M, mainly in the cells infiltrating the damaged mucosa of rats . Administration of a higher than 3.4 M NaCl solution elevated luminal pH of the rat stomach remarkably, enabling bacterial overgrowth and dramatically increasing iNOS expression (n = 5 per concentration) . Pretreatment with ampicillin (p.o), an antibiotic, attenuated the iNOS expression in duplicate experiments . Co-treatment with aminoguanidine (s.q) accelerated recovery of elevated luminal pH at 8 h and 16 h or 24 h after administration of 3.4 M (n = 8) and 5.2 M NaCl solution (n = 5), respectively . iNOS expression and luminal pH elevation were also observed in mice stomachs after administration of 3.4 M NaCl solution . The elevated luminal pH of iNOS-/- mice stomachs after the administration of NaCl solution was significantly lower at 6 h (n = 7) and at 9 h (n = 11), compared to that of wild type mice (n = 9 and 10, respectively) . CONCLUSIONS: Hypertonic NaCl solutions induced iNOS expression in the gastric mucosa . iNOS activity prolonged the elevation of the luminal pH, potentially leading to bacterial overgrowth, which in turn enhanced iNOS expression . This vicious cycle might be related to the promoting effect of NaCl.

Neurol Neurochir Pol, 2003 Jan-Feb, 37(1), 73 - 87
{Serum and cerebrospinal fluid concentration of inflammatory proteins MIP-1-alpha and MIP-1-beta and of interleukin 8 in the course of borreliosis}; Grygorczuk S et al.; Chemokines constitute a group of cytokines with a strong chemotactic action, playing an important role in the pathogenesis of inflammatory responses, including infectious meningitis . The results of in vitro experiments suggest synthesis of chemokines during Borrelia burgdorferi infection . The aim of this study was to investigate serum and cerebrospinal fluid (CSF) concentrations of the following chemokines: interleukin-8 (Il-8) and macrophage inflammatory protein 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) in patients with neuroborreliosis . The study group consisted of 20 patients admitted to Neuroinfections and Infectious Diseases Department of the Medical University in Bialystok . The control group consisted of 12 healthy persons from whom blood samples were obtained, and 10 patients without meningitis, from whom CSF samples were taken for diagnostic purposes . Chemokine concentrations were measured with ELISA kits before treatment (baseline) and after 2 weeks of antibiotic therapy (post-treatment) . Mean serum concentrations of chemokine were elevated in neuroborreliosis patients at baseline (Il-8--mean +/- SD = 668.25 +/- 661.51 pg/ml, MIP-1 alpha--124.90 +/- 89.37 pg/ml, MIP-1 beta--233.40 +/- 298.40 pg/ml) as compared to these in the control group (Il-8-23.72 +/- 7.68 pg/ml, MIP-1 alpha--36.81 +/- 4.74 pg/ml, MIP-1 beta--70.41 +/- 16.41 pg/ml) . Post-treatment mean concentrations of Il-8 (197.70 +/- 285.56 pg/ml) and MIP-1 beta (102.70 +/- 42.56 pg/ml) remained significantly elevated, while the mean concentration of MIP-1 alpha (53.65 +/- 38.50 pg/ml) was insignificantly higher than that in the control group . The Il-8 mean concentration was the most elevated comparing to the controls and has decreased most significantly during the treatment . CSF concentrations of chemokines were significantly elevated both at baseline (Il-8--754.95 +/- 535.83 pg/ml, MIP-1 alpha--24.35 +/- 4.88 pg/ml, MIP-1 beta--27.6 +/- 8.38 pg/ml) and post-treatment (Il-8--98.20 +/- 74.74 pg/ml, MIP-1 alpha--18.60 +/- 2.87 pg/ml, MIP-1 beta--16.90 +/- 4.38 pg/ml) in comparison with the controls (Il-8--10.43 +/- 2.70 pg/ml, MIP-1 alpha--8.17 +/- 1.54 pg/ml, MIP-1 beta--7.27 +/- 1.58 pg/ml) . MIP-1 alpha and MIP-1 beta CSF concentrations were significantly lower than their concentrations in serum . The Il-8 CSF concentration did not differ significantly from its serum concentration . However, in some patients Il-8 CSF concentration was much higher than that in the serum, which suggests its significant synthesis within the cns and its role in the pathogenesis of B . burgdorferi meningitis . Chemokine CSF concentrations were not correlated with cytosis and CSF protein concentration . The results indicate the induction of Il-8, MIP-1 alpha and MIP-1 beta synthesis in the course of neuroborreliosis and a decrease of their concentrations during 2 weeks of treatment, however, without reaching the normal values.

Ann Med Interne (Paris), 2003 May, 154(3), 187 - 9
{Peroneal nerve palsy induced by anterior tibialis pyomyositis}; Caparros-Lefebvre D et al.; A 16-year-old girl from Guadeloup developed paresis of the flexors of the right foot, associated with edema and acute pain located in the upper anterior tibialis muscle . Electromyography confirmed mononeuritis of the right peroneal nerve, with severe reduction of potential amplitude . Computed tomography of the right leg showed a heterogeneous mass involving the upper segment of the anterior tibialis muscle, close to the location of peroneal nerve . Muscle biopsy confirmed pyomyositis . Muscle culture was negative . Paresis improved soon after antibiotic therapy was started.

Fertil Steril, 2003 Aug, 80(2), 450 - 2
Spontaneous expulsion of three large fibroids after uterine artery embolization; Laverge F et al.; OBJECTIVE: To report a case of uneventful expulsion of huge fibroids after uterine artery embolization.Case report . SETTING: The Department of Obstetrics and Gynaecology of a university hospital . PATIENT(S): A 45-year-old woman who underwent uterine artery embolization for fibroids . INTERVENTION(S): Transfemoral selective bilateral uterine artery catheterization and injection of 500-700 microm polyvinyl alcohol particles . RESULT(S): Recovery of the patient.The spontaneous expulsion of three fibroids on three different occasions over several months resulted in a significant reduction in menstrual loss and dysmenorrhea . CONCLUSION(S): Delivering fibroids or sections of fibroids may be a natural process after uterine artery embolization, therefore it is essential to warn women about the possible risk . Close follow-up is also essential . The size of the fibroids discharged did not require hysterectomy . Adequate antibiotic cover may be necessary to prevent sepsis.

Eur J Pharmacol, 2003 Aug 1, 474(1), 31 - 42
Ligand internalization by cloned neuropeptide Y Y5 receptors excludes Y2 and Y4 receptor-selective peptides; Parker SL et al.; In human embryonic kidney-293 (HEK-293) cells, the cloned human neuropeptide Y Y5 receptor saturably internalized agonists, with the rank order of neuropeptide Y-(19-23)-{Gly1,Ser3,Gln4,Thr6,Ala31,Aib32,Gln34}human pancreatic polypeptide (neuropeptide Y-Aib-pancreatic polypeptide)>human neuropeptide Y>porcine peptide YY>{Pro34}human peptide YY>{Leu31,Pro34}human peptide YY>>human peptide YY-(3-36) . Human pancreatic polypeptide competed {125I}neuropeptide Y binding and internalization in neuropeptide Y Y5 receptor-expressing cells, but itself showed no internalization . The internalization was strongly dependent on temperature . The surface binding, and especially the internalization, of human neuropeptide Y were highly sensitive to the clathrin network inhibitor phenylarsine oxide, and to the cholesterol-complexing antibiotic filipin III . The internalized ligands were present in particles corresponding to secondary endosomes in Percoll gradients, but especially in particles banding with the acid hexosaminidase lysosomal marker . At any temperature tested, internalization of the neuropeptide Y Y5 receptor driven by human neuropeptide Y in HEK-293 cells was much slower than the internalization of the neuropeptide Y Y1 receptor reported in the same cells, or in Chinese hamster ovary (CHO) cells . The neuropeptide Y Y5 receptor subtype could be the metabotropic receptor responding to protracted challenges by neuropeptide Y-like peptides, and its density could be little sensitive to concentration of extracellular agonists.

Int J Med Inform, 2003 Jul, 70(2-3), 309 - 16
Which clinical decisions benefit from automation? A task complexity approach; Sintchenko V et al.; OBJECTIVE: To describe a model for analysing complex medical decision making tasks and for evaluating their suitability for automation . METHOD: Assessment of a decision task's complexity in terms of the number of elementary information processes (EIPs) and the potential for cognitive effort reduction through EIP minimisation using an automated decision aid . RESULTS: The model consists of five steps: (1) selection of the domain and relevant tasks; (2) evaluation of the knowledge complexity for tasks selected; (3) identification of cognitively demanding tasks; (4) assessment of unaided and aided effort requirements for this task accomplishment; and (5) selection of computational tools to achieve this complexity reduction . The model is applied to the task of antibiotic prescribing in critical care and the most complex components of the task identified . Decision aids to support these components can provide a significant reduction of cognitive effort suggesting this is a decision task worth automating . CONCLUSION: We view the role of decision support for complex decision to be one of task complexity reduction, and the model described allows for task automation without lowering decision quality and can assist decision support systems developers.

Clin Lab, 2003, 49(7-8), 319 - 27
Evaluation of a fully automated procalcitonin chemiluminescence immunoassay; Hubl W et al.; We evaluated a new fully automated microparticle immunoassay for procalcitonin (LIAISON BRAHMS PCT) in comparison with a previously established manual chemiluminescence assay from the same manufacturer (LUMItest PCT, BRAHMS AG) . Procalcitonin (PCT) is an early and rather specific marker of systemic bacterial infection . In addition, the efficacy of antibiotic therapy can be monitored by sequential analysis of PCT values . This is why rapid and accurate determinations of PCT are urgently required by intensive care units . The aim of this study was to evaluate in a clinical set-up a new fully automated rapid PCT test . Analytical results are compared with results obtained by a previously introduced quantitative manual test . Intra-assay coefficients of variation (CV) were found in the range of 0.94 to 7.1% at concentrations between 0.46 and 97.2 microg/l . Over a time period of 27 days the inter-assay CV was found below 4.0% at concentrations of 1.93 and 14.29 microg/l and 9.9% at 0.40 microg/l . The functional sensitivity at a CV level of 20% was determined as 0.2 microg/l . Linearity could be demonstrated in a concentration range from 0 to 445 microg/l . When serum and plasma with EDTA, citrate or heparin anti-coagulation were analyzed in parallel, no systematic bias was found . A method comparison by regression analysis showed PCT values determined by both tests in very good agreement (r = 0.99) . PCT concentrations in apparently healthy subjects (n =101) were below 0.58 microg/l in line with previously published results . Patients with sepsis (n = 43) or with infectious adult respiratory distress syndrome (ARDS) (n = 28) showed median values of 22.2 and 18.9 microg/l, respectively . In a clinical set-up the LIAISON Brahms PCT assay provided rapid and accurate PCT results supporting the early detection of severe sepsis, the differentiation between systemic bacterial infection and other inflammatory diseases, and the monitoring of antibiotic therapy in septic patients . The results of the new LIAISON BRAHMS PCT assay show an excellent concordance with the LUMItest PCT . The clinical information derived from the measurements is well comparable to the results obtained with the LUMItest PCT, too.

Science, 2003 Aug 8, 301(5634), 802 - 3
Bacterial sex: playing voyeurs 50 years later; Kohiyama M et al.; The concept of chromosomes with a ring structure was born during the early studies of bacterial sexuality, and the discovery of fertility factors- episomes or plasmids-provided much later the key tools for gene cloning and biotechnology . But the plasmid-mediated transfer of antibiotic and other resistances, as well as pathogenicity, has served bacteria well in their own adaptive evolution.

Int J Pediatr Otorhinolaryngol, 2003 Sep, 67(9), 1023 - 6
An 8-year-old boy with a Pott's puffy tumor; Huijssoon E et al.; An 8-year old boy with a history of trauma, sinusitis and a swelling of the frontal bone with somnolence was diagnosed with a Pott's puffy tumor (PPT) . Minimal invasive surgical intervention was performed together with a strict regimen of antibiotic therapy . In this case debridement of the frontal bone was not necessary . Serial X-ray imaging of the skull showed complete ossification of the frontal bone lesion . Early diagnosis using thorough radiological evaluation is necessary to effectuate the proper therapeutic approach . For this reason, a patient with a forehead swelling and a history of trauma and/or sinusitis should be suspected for a PPT.

J Oral Maxillofac Surg, 2003 Aug, 61(8), 871 - 6
A clinical evaluation of dry socket in a Nigerian teaching hospital; Oginni FO et al.; PURPOSE: We sought to determine the incidence of dry socket in a Nigerian teaching hospital and to evaluate the patients' demographic pattern, predisposing factors, the treatment given, and treatment outcome . Patients and Methods: A retrospective review of records of dental extractions complicated by dry socket in Obafemi Awolowo University Teaching Hospital, Ile-Ife, between January 1996 and December 2000 was undertaken . Information retrieved included patient sociodemographic data, indications for extraction, tooth extracted, status of attending surgeon, onset of symptoms, relevant findings of the examining clinician, interval before presentation, treatment given, and its outcome . RESULTS: Of the 3,319 dental extractions performed in 3,008 patients, 136 (4.1%) were complicated by dry socket . The patients' mean age was 33.4 (15.4) years and a peak age incidence of 21 to 30 years was found . A slight female preponderance (1.4:1) was observed . The majority of patients were in the low-income group, and presentation in the hospital was prompt in the high-income group . Mandibular teeth were affected 3 times more than maxillary teeth (P =.00080) . Most cases of dry socket resulted from extractions performed by undergraduates and house officers . Various underlying systemic conditions were found in 11.0% of cases, none of which included use of oral contraceptives . Treatment was usually the use of zinc oxide eugenol dressing in an irrigated socket, combined with antibiotic therapy in 45.3% of cases . No adverse reaction to zinc oxide eugenol was observed . CONCLUSION: The incidence of dry socket in our hospital is 4.1% . The mandible was involved 3 times more than the maxilla . With the use of zinc oxide eugenol dressing, 70.6% of patients completed treatment satisfactorily and 29.2% were lost to follow-up.

Gynecol Obstet Invest, 2003, 55(4), 231 - 4
Laparoscopy-assisted vaginal hysterectomy clinical pathway . A multivariate analysis of impact on costs and quality of care; Chang WC et al.; Numerous studies have demonstrated that a well-designed clinical pathway is an effective means of sustaining quality while controlling costs in the management of certain disease entities . We evaluated the impact that cost and medical quality have on the implementation of a clinical pathway for laparoscopy-assisted vaginal hysterectomy (LAVH) . This retrospective study involved a sample of 124 patients who underwent LAVH in a medical center in central Taiwan . Patients were divided into two groups on the basis of whether they received treatment before or after implementation of the LAVH clinical pathway . The preclinical pathway group was comprised of 40 patients who underwent LAVH before clinical pathway implementation (May-December 1997) . The clinical pathway group included 84 patients who underwent LAVH after implementation of the clinical pathway (January 1998-March 1999) . In order to study the impact of the LAVH clinical pathway, patient characteristics were controlled by multiple linear regression . The results showed a significant reduction in cost, average length of hospital stay, and average duration of surgery and anesthesia (p < 0.01) . Dependent nominal variables for clinical indicators like postoperative intravenous fluid and injection of antibiotics 48 h after surgery, and complications were analyzed by a logistic regression model . The results noted better control of antibiotic intravenous injection 48 h after surgery in the clinical pathway group (p = 0.03) . The other indicators included delay of operation day, blood transfusion, patient mortality, and patients readmitted within 2 weeks . There was one operation day delay and one readmission within 2 weeks of discharge in the preclinical pathway group . Based on our results, the implementation of a clinical pathway for LAVH contains cost while maintaining quality of care, especially when the medical fees are paid under the case payment system .

Gynecol Obstet Invest, 2003, 55(4), 211 - 5
Tubo-ovarian abscess in older women: is the woman's age a risk factor for failed response to conservative treatment?
Halperin R, Levinson O, Yaron M, Bukovsky I, Schneider D.
OBJECTIVE: To assess retrospectively if there is a trend of change in the epidemiology of tubo-ovarian abscess (TOA) and to define the epidemiologic, clinical and laboratory risk factors associated with failed response to conservative antibiotic therapy . STUDY DESIGN: The charts of 60 patients, admitted with clinically and sonographically diagnosed TOA between January 1995 and December 2000, were reviewed . On admission, all patients were treated with broad-spectrum antibiotics, and were divided into two groups according to the response to medical treatment . Forty-three patients, responding to antibiotic therapy, constituted group A, whereas 17 patients who did not respond and were further treated by sonographically guided drainage or surgery, were included in group B . The groups were compared with respect to patient characteristics, clinical and sonographic presentation, laboratory findings, duration of hospital stay and recovery rate of different pathogens from the endocervix . RESULTS: The mean age of patients responding to medical therapy (group A) was significantly lower (39.6 +/- 8.3) than the age of patients who did not respond (group B) (45.3 +/- 6.6) (p = 0.02) . The gravidity as well as the percentage of menopausal women were significantly increased in group B (p = 0.03 and p = 0.02, respectively) . There was a significantly lower incidence of previous pelvic surgery and past history of PID in group B versus group A (p = 0.02 and p = 0.03, respectively), yet the duration of IUD use was significantly prolonged in group B (p = 0.02) . The size of TOA, evaluated clinically and sonographically, was significantly increased in group B compared with group A (p = 0.04 and p = 0.009, respectively) . Pelvic peritonitis was observed in 40% of group B patients and in none of group A patients (p = 0.0001) . The only laboratory finding differentiating between the two groups was the mean sedimentation rate, being significantly higher in group B than in group A (p = 0.0005) . The time interval from admission to afebrile condition as well as the duration of hospitalization were significantly shorter in group A (6.1 +/- 2.3 days) than in group B (10.7 +/- 4.7 days) (p = 0.00003) . The incidence of positive culture from the endocervix was significantly higher in group B than in group A (p = 0.007) . One hundred percent of patients in group B versus 65.2% of patients in group A were treated with triple agent therapy (p = 0.007) . CONCLUSION: The results of the current study strengthen our previous assumption that there is probably a new trend in the epidemiology of TOA, occurring in older women, who do not present the traditional risk factors for pelvic inflammatory disease and TOA .

Microbiology, 2003 Aug, 149(Pt 8), 2183 - 91
CloN2, a novel acyltransferase involved in the attachment of the pyrrole-2-carboxyl moiety to the deoxysugar of clorobiocin; Xu H et al.; The aminocoumarin antibiotic clorobiocin contains a 5-methylpyrrole-2-carboxylic acid unit, attached via an ester bond to the 3-OH group of the deoxysugar moiety . To investigate candidate genes responsible for the formation of this ester bond, a gene inactivation experiment was carried out in the clorobiocin producer Streptomyces roseochromogenes var . oscitans DS 12.976 . An in-frame deletion was created in the coding sequence of the gene cloN2 . The production of secondary metabolites in the wild-type and in the cloN2 mutant was analysed . The wild-type showed clorobiocin as the main product, whereas the cloN2 mutant accumulated a new aminocoumarin derivative, novclobiocin 104, lacking the pyrrole moiety at the 3-OH of the deoxysugar . In addition, free pyrrole-2-carboxylic acid accumulated in the culture extract of the cloN2 mutant . The structures of the metabolites were confirmed by NMR and LC-MS analysis . Clorobiocin production was successfully restored in the cloN2 mutant by introducing a replicative plasmid containing the cloN2 sequence . These results prove an involvement of cloN2 in the formation of the ester bond between the pyrrole moiety and the deoxysugar in clorobiocin biosynthesis . Furthermore, they indicate that the C-methylation at position 5 of the pyrrole moiety occurs after the attachment of pyrrole-2-carboxylic acid unit to the deoxysugar moiety.

Microbiology, 2003 Aug, 149(Pt 8), 1991 - 2004
Control of growth, secondary metabolism and sporulation in Streptomyces venezuelae ISP5230 by jadW(1), a member of the afsA family of gamma-butyrolactone regulatory genes; Wang L et al.; Three new genes (jadW(1), jadW(2) and jadW(3)) were isolated from a region of the Streptomyces venezuelae ISP5230 chromosome at the left-hand end of the jad cluster for jadomycin B (JdB) biosynthesis . The deduced amino acid sequence of jadW(1) showed strong similarity to gene products associated in several streptomycetes with gamma-butyrolactone autoregulators controlling morphological differentiation and secondary metabolism . Examination of JadW(1) for conserved domains detected a repeat sequence characteristic of proteins in the AfsA regulatory family . Insertional inactivation of jadW(1) reduced the growth rate of S . venezuelae cultures in aerated liquid media containing complex nitrogen sources and altered growth morphology in minimal medium . It also affected sporulation on agar media . Cultures of jadW(1)-disrupted mutants grown under conditions supporting biosynthesis of JdB or chloramphenicol by the wild-type strain failed to produce either of the antibiotics . Complementing the disrupted strain by transformation with pJV435, containing a cloned copy of the gene, improved sporulation and restored antibiotic biosynthesis in transformants to titres close to those of the wild-type similarly transformed with pJV435 as a control . The results are consistent with a role for jadW(1) in regulating morphological and metabolic differentiation . Further sequence analysis of jadR(2), which functions with jadR(1) in stress-induced activation of JdB biosynthesis, indicated that this gene encodes a gamma-butyrolactone receptor homologue . The growth-rate-sensitive phenotype of the jadW(1)-disrupted mutant, and the proximity of jadW(1) to jadR(2) indicate that this region of the jad gene cluster contains a regulatory mechanism incorporating gamma-butyrolactone signalling and sensitivity to environmental stress.

Nucleic Acids Res Suppl, 2002, (2), 95 - 6
Distamycin A, a minor groove binder, changes enediyne-induced DNA cleavage sites and enhances apoptosis; Hiraku Y et al.; We examined the effects of a minor groove binder, distamycin A, on DNA cleavage and apoptosis induced by an enediyne antitumor antibiotic, C1027, using 32P-labeled DNA fragments obtained from human genes . C1027 alone induced DNA cleavage particularly at the 5'-TTTT-3'/3'-AAAA-5' sequence (cutting sites are underlined) . The addition of distamycin A enhanced the double-strand DNA cleavage at the 5'-CCT-3'/3'-GGA-5' and 5'-CCA-3'/3'-GGT-5' sequences, with a two-nucleotide 3'-stagger of the cleaved residues . These results suggest that distamycin A forms a heterodimer with C1027 to bind to DNA at GC-rich regions, resulting in amplification of DNA cleavage at these regions . Distamycin A enhanced C1027-induced DNA ladder formation and cytotoxicity in HL-60 cells . Therefore, amplification of DNA cleavage at GC-rich regions may result in enhancement of apoptosis . The present study on amplifiers of antitumor agents showed a novel approach to the potentially effective antitumor therapy.

Lancet Infect Dis, 2003 Aug, 3(8), 507 - 14
Is Crohn's disease caused by a mycobacterium? Comparisons with leprosy, tuberculosis, and Johne's disease; Greenstein RJ; Although Crohn's disease is considered to be autoimmune in origin, there is increasing evidence that it may have an infectious cause . The most plausible candidate is Mycobacterium avium subspecies paratuberculosis (MAP) . Intriguingly, Koch's postulates may have been fulfilled for MAP and Crohn's disease, even though they still have not been met for Mycobacterium leprae and leprosy . In animals MAP causes Johne's disease, a chronic wasting intestinal diarrhoeal disease evocative of Crohn's disease . Johne's disease occurs in wild and domesticated animals, including dairy herds . Viable MAP is found in human and cow milk, and is not reliably killed by standard pasteurisation . MAP is ubiquitous in the environment including in potable water . Since cell-wall-deficient MAP usually cannot be identified by Ziehl-Neelsen staining, identification of MAP in human beings requires culture or detection of MAP DNA or RNA . If infectious in origin, Crohn's disease should be curable with appropriate antibiotics . Many studies that argue against a causative role for MAP in Crohn's disease have used antibiotics that are inactive against MAP . However, trials that include macrolide antibiotics indicate that a cure for Crohn's disease is possible . The necessary length of therapy remains to be determined . Mycobacterial diseases have protean clinical manifestations, as does Crohn's disease . The necessity of stratifying Crohn's disease into two clinical manifestations (perforating and non-perforating) when interpreting the results of antibiotic therapy is discussed . Rational studies to evaluate appropriate therapies to cure Crohn's disease are proposed.

Lancet Infect Dis, 2003 Aug, 3(8), 476 - 88
Evaluation of outcomes in community-acquired pneumonia: a guide for patients, physicians, and policy-makers; Barlow GD et al.; Community-acquired pneumonia (CAP) is a key target for research and quality improvement in acute medicine . However, many of the outcome measures used in prognostic and antibiotic studies are not validated and do not capture features of outcome that are important to patients . Substitutes for traditional outcome measures include a recently validated patient-based symptom questionnaire (the CAP-Sym) and process-of-care measures . The interpretation of outcomes also depends on the quality of the study design and methods used . This paper discusses the advantages and disadvantages of outcome, process-of-care, and economic measures in CAP and the interpretation of these measures in randomised and observational studies . A core set of measures for use in clinical CAP research and performance measurement is proposed.

Cancer Sci, 2003 Aug, 94(8), 686 - 91
Distinct mechanisms of site-specific oxidative DNA damage by doxorubicin in the presence of copper(II) and NADPH-cytochrome P450 reductase; Mizutani H et al.; The anticancer mechanism of doxorubicin (DOX), an anthracycline antibiotic, is believed to involve DNA damage through topoisomerase II inhibition and free radical generation . The free radical generation may also participate in genotoxicity, as well as cardiotoxicity, in normal human cells . The present study showed that DOX generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), an indicator of oxidative DNA damage, in HL-60 cells, but not in H(2)O(2)-resistant HP100 cells, suggesting the involvement of H(2)O(2) in cellular DNA damage . Since DOX has both p-quinone and p-hydroquinone residues, free radical generation can be initiated by either reduction or oxidation of DOX . To clarify whether the oxidized or reduced form is more important for DOX-induced H(2)O(2) generation, we investigated the site-specific DNA damage induced by DOX in the presence of Cu(II), in comparison with that in the presence of cytochrome P450 reductase, using (32)P-labeled DNA fragments . DOX caused DNA damage in the presence of Cu(II) or cytochrome P450 reductase . The degree of Cu(II)-mediated DNA damage, including 8-oxodG formation, was much greater than that of cytochrome P450 reductase-mediated DNA damage . DOX plus Cu(II) caused DNA damage specifically at guanine, thymine and cytosine residues, particularly at 5'-GG-3', 5'-GT-3' and 5'-TG-3' sequences . Scavenger experiments suggested the involvement of reactive species generated from H(2)O(2) and Cu(I) . When cytochrome P450 reductase and NADPH were used instead of Cu(II), every nucleotide was uniformly damaged, suggesting the participation of.OH . We conclude that DOX may induce carcinostatic and genotoxic effects through oxidation of its p-hydroquinone moiety by metal ion rather than through p-quinone reduction by cytochrome P450 reductase.

New Microbiol, 2003 Jul, 26(3), 275 - 80
Resistance emergence among P . aenrginosa in a rat thigh-abscess model . Comparison of imipenem and meropenem treatment; Karadenizli A et al.; Resistance emergence to carbapenem antibiotics was studied in a rat-thigh abscess model . Abscesses were developed in three groups with a total of 15 P . aeruginosa strains (three rats per strain) . Groups were assigned to imipenem or meropenem treatment while one was left antibiotic-free . Test strains were fully susceptible to these antibiotics and the "Mutant Preventing Concentrations" of imipenem and meropenem over these strains were comparable . Antibiotic serum levels, assessed by serum bioassay test, were similar among therats . After four days, rats (n=45) were sacrificed and carbapenem resistant mutants were selected on imipenem (4 mg/L) and meropenem (4 mg/L) supplemented agar plates . Resistant variants of three strains, from four abscesses, were detected; one in the meropenem group, two in the imipenem and one in the untreated group . The MICs of imipenem and meropenem for the mutants were increased fourfold times or even higher of their counterparts . Resistance emergence under antibiotic pressure in P . aeruginosa has been shown in various conditions . To our knowledge, however, resistance emergence in abscess and also the comparison of imipenem and meropenem in this regard has not been studied before.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 2001 Dec, 23(6), 563 - 7
{Antitumor effect of lidamycin-containing monoclonal antibody immunoconjugate with downsized-molecule}; Liu XY et al.; OBJECTIVE: To develop a novel monoclonal antibody (mAb) immunoconjugate with downsized-molecule and highly potent antitumor effects . METHODS: The mAb conjugate was prepared by linking lidamycin (LDM), an antitumor antibiotic with extremely potent cytotoxicity, to mAb Fab' fragment . The molecular weight of Fab'-LDM was determined by non-reduced SDS-PAGE . The immunoreactivity of Fab'-LDM conjugate with cancer cells was detected by ELISA . The antitumor activity of the conjugate was determined by MTT assay, clonogenic assay, and animal model of transplantable colon carcinoma 26' (C26) in mice . RESULTS: The relative molecular mass of Fab'-LDM conjugate was approximately 65,000, suggesting a molar ratio of 1:1 between Fab' fragment and LDM in the conjugate . Fab'-LDM was reactive with hepatoma BEL-7402 and colon carcinoma 26 cells, but not reactive with KB cells . The cytotoxicity of Fab'-LDM conjugate to BEL-7402 cells, the antigen relevant cancer cells, was 13-fold more potent than that of free LDM, while the cytotoxicity of Fab'-LDM conjugate against C26 cells was 5.5-fold more potent than that of free LDM . However, the cytotoxicity of Fab'-LDM conjugate to KB cells, the antigen irrelevant cells, was similar to that of free LDM . Given by 3 intravenous injections, on day 1, 4 and 7, Fab'-LDM conjugate at doses of 0.05 mg/kg, 0.1 mg/kg and 0.2 mg/kg markedly suppressed the growth of colon carcinoma 26 in mice by 80%, 92% and 94%, respectively, whereas free LDM at 0.1 mg/kg suppressed the growth by 77% . The survival time of tumor-bearing mice was also increased by Fab'-LDM conjugate treatment . Fab'-LDM conjugate was more effective than equivalent unconjugated LDM (P < 0.01) . CONCLUSIONS: The immunoconjugate composed of LDM and Fab' fragment that is characterized by downsized-molecule shows remarkable effectiveness against tumor growth.

Am J Kidney Dis, 2003 Aug, 42(2), E27 - 31
ANCA-positive crescentic glomerulonephritis associated with minocycline therapy; Sethi S et al.; Minocycline is an oral antibiotic widely used for the long-term treatment of acne and rheumatoid arthritis . A few patients develop antineutrophil cytoplasmic antibodies (ANCAs) during minocycline therapy . In this report, the authors describe a case of severe pauci-immune crescentic and necrotizing glomerulonephritis associated with positive cytoplasmic ANCA (C-ANCA) titers and proteinase 3 (PR3) levels after minocycline therapy . Discontinuation of minocycline and initiation of immunosuppressive treatment resulted in improvement of renal function and decline in C-ANCA titers and PR3 levels . A high degree of suspicion, testing for ANCA titers, prompt discontinuation of the drug, and initiation of immunosuppressive treatment are crucial to the diagnosis and treatment of drug-induced ANCA-associated glomerulonephritis.

Am J Kidney Dis, 2003 Aug, 42(2), 315 - 24
A multicenter, prospective, randomized, comparative evaluation of dual- versus triple-lumen catheters for hemodialysis and apheresis in 485 patients; Contreras G et al.; BACKGROUND: The purpose of this study is to compare a new temporary triple-lumen catheter (TLC) for dialysis that has a third lumen devoted to fluid and medication administration or blood sampling with a marketed dual-lumen catheter (DLC) . METHODS: Four hundred eighty-five patients referred for acute hemodialysis or apheresis were randomly assigned to either a TLC or DLC in a multicenter, prospective, randomized trial . RESULTS: Analysis of blood flow rates was completed on 464 patients (228 patients, DLC; 236 patients, TLC) with a total of 1,681 hemodialysis (808 treatments, DLC; 873 treatments, TLC) and 82 apheresis treatments (37 treatments, DLC; 45 treatments, TLC) . During hemodialysis, a median achieved flow rate (AFR) of 267 mL/min was realized for both groups (P = 0.58) . During apheresis, a median AFR of 72.5 mL/min (range, 50 to 150 mL/min) was achieved in the DLC group, and 87 mL/min (range, 60 to 150 mL/min), in the TLC group (P = 0.14) . Three hundred ninety-three patients (193 patients, DLC; 200 patients, TLC) had blood and catheter tip cultures performed on removal, and catheter-related bloodstream infection (CRBSI) status was determined . Thirty-one patients (7.9%) had a CRBSI: 16 patients (8.3%), DLC; and 15 patients (7.5%), TLC (P= 0.77) . Incidence densities of CRBSI were 12.4/1,000 DLC-days and 10.2/1,000 TLC-days (P = 0.59) . The CRBSI incidence of 18.2/1,000 catheter-days for femoral sites was significantly greater than the 7/1,000 catheter-days for jugular sites (P = 0.02) and 6.6/1,000 catheter-days for combined jugular and subclavian sites (P = 0.01) . In multivariate analysis, antibiotic use was the only factor related to CRBSI (odds ratio, 0.30; 95% confidence interval, 0.12 to 0.76) . There were no statistically significant differences in rates of other complications between the 2 catheters . CONCLUSION: Results show that the new TLC is similar to the marketed DLC.

Ann Surg Oncol, 2003 Aug, 10(7), 778 - 82
Prospective identification of risk factors for wound infection after lower extremity oncologic surgery; Morris CD et al.; BACKGROUND: Surgical site infections (SSI) are frequent causes of morbidity and mortality after orthopaedic oncologic procedures . This study was conducted to identify the surgical site infection rate following a lower extremity or pelvic procedure and assess the risk factors for acquiring SSI by direct observation of orthopaedic oncology patients' wounds at a comprehensive cancer center . METHODS: One hundred ten consecutive patients were prospectively studied . The surveillance of surgical site infections was carried out by a surgeon-trained nurse from the Infectious Disease Service . Nineteen variables were analyzed as risk factors . RESULTS: The overall SSI rate was 13.6% (15 of 110) . Excluding those patients with known preoperative infections, the SSI rate was 9.5% (10 of 105) . Two statistically significant risk factors for surgical site infection in these patients emerged in the multivariate analysis: blood transfusion (P =.007) and obesity (P =.016) . Procedure category was significant in univariate analysis only . Preoperative length of stay, length of procedure, prior adjuvant treatment (chemotherapy or radiotherapy), prior surgery, and use of an implant or allograft were not statistically significant risk factors for wound infection . Antibiotic usage patterns did not influence SSI rate . CONCLUSIONS: Blood transfusion and obesity should be considered individual risk factors for the development of wound infection in patients having orthopaedic oncologic procedures.

Surg Neurol, 2003 Aug, 60(2), 120 - 3; discussion 123
Penetrating head wound: a remarkable case; Ardill W et al.; BACKGROUND: The modern management of penetrating head injuries is generally considered a neurosurgical specialty that relies heavily on the use of sequential imaging techniques, an ever-changing armamentarium of sophisticated antibiotics and specific neurosurgical operative skills . Unfortunately these optimal therapeutic components are frequently not available to patients injured in underdeveloped countries . METHODS: An unusual case of a young patient suffering a penetrating brain wound and undergoing delayed treatment in an African mission hospital is reviewed . RESULTS: A functional but neurologically impaired outcome resulted from limited surgical debridement and short-term broad-spectrum antibiotic administration . CONCLUSIONS: The multiple exigencies of surgical practice in an underdeveloped African nation do not preclude successful management of penetrating head trauma.

FEMS Microbiol Lett, 2003 Aug 8, 225(1), 53 - 7
A gene transfer system for the glycopeptide producer Nonomuraea sp . ATCC39727; Stinchi S et al.; The filamentous actinomycete Nonomuraea sp . ATCC39727 produces the industrially important glycopeptide antibiotic A40926 . We developed a gene transfer system based on intergeneric conjugation from Escherichia coli . Analysis of the ex-conjugants revealed that the incoming plasmid pSET152 had integrated at two sites in the Nonomuraea genome . One of these was characterized and found to be highly related to other PhiC31 attB sites described in Streptomyces spp., including the core TTS sequence, where crossover occurs . Surprisingly, pSET152 was also found in episomic form in the Nonomuraea ex-conjugants.

FEMS Microbiol Lett, 2003 Aug 8, 225(1), 35 - 40
BldD from Streptomyces coelicolor is a non-essential global regulator that binds its own promoter as a dimer; Elliot MA et al.; We have shown that the bldD gene of Streptomyces coelicolor, while required for antibiotic production and morphological differentiation, is not essential for viability . We have also demonstrated that BldD forms a higher order complex both in solution and when bound to target DNA . Purified BldD exists in three forms in solution, as a tetramer, dimer and monomer, but only in the dimeric form when bound to its own promoter/operator.

Zhonghua Yi Xue Za Zhi, 2003 May 10, 83(9), 713 - 8
{Clinical analysis of 190 cases of outbreak with atypical pneumonia in Guangzhou in spring, 2003}; Zhao ZW et al.; OBJECTIVE: To study methods of diagnosis and treatment for atypical pneumonia (Severe Acute Respiratory Syndrome), outbreak of the illness in Guangzhou during Jan . - Mar., 2003 . METHODS: 190 cases with atypical pneumonia were analyzed, and the cases were admitted in Guangzhou municipal First Hospital and Guangzhou municipal Eighth Hospital . RESULTS: Patients were infected by close quarters contacting each other . All patients manifest high fever, and accompany by dyspnea, cough, palpitate, weakness, headache and swirl . Other 46 cases were accompanied by diarrhea . Most of patients, manifestation of lungs was negative . Chest X-ray, shadow of lungs were light in beginning, and change to severity slowly or suddenly during 5 - 10 days . Of these cases, 36 cases develop to ARDS and 11 cases died with severity ARDS . Using general antibiotic was of no effect for the illness . Continual positive airway pressure (CPAP) and glucocorticoid was required that can control deprivation of the disease when toxicosis symptom of patients was severity and shadow of lungs diffuse more and more . CONCLUSION: Infectivity of the illness is evidence and spread by airway . Using general antibiotic was of no effect for the illness . Continual positive airway pressure (CPAP) and glucocorticoid are effective for control of the disease.

Ann Univ Mariae Curie Sklodowska {Med}, 2002, 57(1), 167 - 73
Histological changes in the pancreas of white rats after administering cephalexin and ethanol; Zarebska A et al.; The research was conducted on male Wistar rats weighing approximately 200 g . Animals of experimental group I were administered 20% ethyl alcohol for drinking, animals of experimental group II--cephalexin in the dose of 42 mg daily, animals of experimental group III--simultaneously alcohol and cephalexin in the mentioned doses . After 10 days the animals were guillotined and pancreas was taken for research . On paraffin sections 7 mu thick there were carried out H + E stain and PAS reaction aimed at discovering neutral mucopolysaccharides . After administering alcohol there was stated a decrease in the activity of exocrime cells and after administering of cephalexim--an increase in this activity . A simultaneous administration of ethyl alcohol and antibiotic causes trophic changes, which can be noticed as introductory, but at this stage--reversible, degenerative changes.

Biosens Bioelectron, 2003 Oct 1, 18(11), 1379 - 83
Monitoring the cellular activity of a cultured single cell by scanning electrochemical microscopy (SECM) . A comparison with fluorescence viability monitoring; Kaya T et al.; The respiratory activities of cultured HeLa cells were monitored at a single cell level using scanning electrochemical microscopy (SECM) that produces images of the localized distribution of oxygen around the cell . The change in the cellular activity was traced after exposures to KCN, ethyl alcohol and the antibiotic drug, Antimycin A . The results were compared with those from the conventional fluorescence monitoring using Calcein-AM that is sensitive to deformation of the cell membrane . The SECM-based measurement follows the decrease in the cellular activity upon exposure to KCN and Antimycin A more rapidly than the fluorescence-based measurements, demonstrating that SECM is suitable for studying the cellular influence of respiration inhibitors.

Biomaterials, 2003 Aug, 24(18), 3005 - 12
Synergistic effect of bismuth subgallate and borneol, the major components of Sulbogin, on the healing of skin wound; Mai LM et al.; Most skin lesions heal delay and even heal efficiently within 1-2 weeks, the healed tissue is neither aesthetically nor functionally perfect . Therefore, facilitating skin healing rate and controlling healed skin quality are major aims of drug treatment for a wound event . Bismuth subgallate (BS) and Borneol (BO) are the two components of Sulbogin, a new Vaseline-based wound healing ointment, one for treating skin wounds . Although BO has antibiotic function, while BS is widely used clinically, neither has been used specifically for wound healing.The experiment described here aimed to study the effect of BS and BO on the healing of skin wounds . This study also compared the effects of BS and BO with Flamazine cream, which is currently the most popular drug for wound healing in hospitals . Full-thickness wounds (3 cm x 3 cm x 0.2 cm) were created on the back of adult male Sprague-Dawley rats . BS, BO, BS+BO, and Flamazine were then evenly applied to cheesecloth and placed over the lesion areas . The drug patches were replaced every 2-3 days until the wound areas were completely covered by epidermis in any kinds of drug treatment . The combined BS and BO treatment had the best effect on healing by decreasing lesion area, while increasing granulation tissue formation, re-epithelialization, eating behavior and reconstitution of skin appendages . This investigation showed that BS and BO have a synergistic effect on the skin wound restoration.

Chin Med Sci J, 2002 Mar, 17(1), 1 - 6
Antitumor effects of monoclonal antibody Fab' fragment-containing immunoconjugates; Liu X et al.; OBJECTIVE: Using monoclonal antibody (mAb) Fab' fragment to develop mAb immunoconjugates for cancer . METHODS: Fab' fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DT), while Fab' fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by beta-mercaptoethanol . The conjugation between Fab' fragment and pingyangmycin (PYM), an antitumor antibiotic, was mediated by dextran T-40 . Immunoreactivity of Fab'-PYM conjugates with cancer cells was determined by ELISA, and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay . Antitumor effects of the Fab'-PYM conjugates were evaluated by subcutaneously transplanted tumors in mice . RESULTS: The molecular weight of Fab' fragment was approximately 53 kD, while the average molecular weight of Fab'-PYM conjugate was 170 kD . The Fab'-PYM conjugates showed immunoreactivity with antigen-relevant cancer cells and selective cytotoxicity against target cells . Administered intravenously, Fab'-PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb . CONCLUSION: Fab'-PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth, suggesting its therapeutic potential in cancer treatment.

Analyst, 2003 Jul, 128(7), 871 - 8
Quantitative analysis of oxytetracycline and its 4-epimer in calf tissues by high-performance liquid chromatography combined with positive electrospray ionization mass spectrometry; Cherlet M et al.; Tetracycline antibiotics are commonly used in veterinary medicine because of their broad spectrum activity and cost effectiveness . Oxytetracycline (OTC) is one of the most important members of this antibiotic family . The purpose of this study was to develop and validate a method to determine OTC residues in edible tissues of calf . Extraction of OTC and its 4-epimer (4-epiOTC), in the presence of the internal standard demethylchlortetracycline (DMCTC), was performed using a liquid extraction with sodium succinate solution (pH 4.0), followed by protein removal with trichloroacetic acid and paper filtration . Further solid-phase extraction clean-up on an HLB polymeric reversed phase column was performed to obtain an extract suitable for LC-MS-MS analysis . Chromatographic separation of the internal standard, and especially OTC and its 4-epimer, was achieved on a PLRP-S polymeric reversed phase column, using a mixture of 0.001 M of oxalic acid, 0.5% (v/v) of formic acid and 3% (v/v) of tetrahydrofuran in water (mobile phase A) and tetrahydrofuran (mobile phase B) as the mobile phase, and at a column temperature of 60 degrees C . OTC and its 4-epimer could be identified using the MS-MS detection technique, and were subsequently quantified . The method has been validated according to the requirements of the EC at the MRL (maximum residue limit, 100 ng g(-1) for muscle, 300 ng g(-1) for liver and600 ng g(-1) for kidney), half the MRL and double the MRL levels, as well for OTC as for 4-epiOTC . Calibration graphs were prepared for all tissues and good linearity was achieved over the concentration ranges tested (r > 0.99 and goodness of fit < 10%) . Limits of quantification of half the MRLs were obtained for the analysis of OTC and 4-epiOTC in muscle, liver and kidney tissues of calf . Limits of detection ranged for both components between 0.8 and 48.2 ng g(-1) . The within-day and between-day precisions, expressed as RSD values, were all below the maximum allowed RSD values calculated according to the Horwitz equation . The results for accuracy fell within the -20% to +10% range . Recoveries were between 47 and 56% for OTC, and between 52 and 62% for 4-epiOTC, depending on the tissue . The method has been successfully used for the quantitative determination of OTC and 4-epiOTC in tissue samples of calves medicated with OTC by intramuscular injection.

Polim Med, 2003, 33(1-2), 41 - 5
The treatment of massive prosthetic grafts infections with the use of silver/collagen coated dacron vascular prosthesis; Pupka A et al.; In this paper the use of silver-coated medical prosthesis of massive aorto-bifemoral and ilio-femoral dacron graft infection with hemorrhage is presented . To solve this problem in situ replacement was attempted using silver-coated dacron vascular prosthesis more resistant to infection . 9 patients with this therapeutic method is reported . Although positive clinical effect was obtained, the scintigraphy and Duplex Doppler Ultrasound of implanted graft revealed its infection . In our opinion therefore application of silver-coated medical prosthesis should be very cautious and limited to the critical states.

Am J Med, 2003 Aug 1, 115(2), 91 - 6
Long-term follow-up of patients with culture-confirmed Lyme disease; Nowakowski J et al.; PURPOSE: To determine the long-term outcome of patients with culture-confirmed Lyme disease . METHODS: We analyzed data collected prospectively on adult patients from a highly endemic area in New York State who were diagnosed with early Lyme disease between 1991 and 1994 . Patients with culture-confirmed erythema migrans were evaluated at baseline, 7 to 10 days, 21 to 28 days, 3 months, 6 months, 1 year, and annually thereafter . All patients were treated with antibiotics at the time of diagnosis . RESULTS: We evaluated 96 cases on 709 separate occasions (median, eight evaluations per case) . The erythema migrans rash resolved within 3 weeks in all of the 94 evaluable cases, none of whom developed an objective extracutaneous manifestation of Lyme disease . Of the 81 cases who were followed for >/=1 year, all but 8 (10%) were asymptomatic at their last visit, a mean (+/- SD) of 5.6 +/- 2.6 years into follow-up, and only 3 (4%) were symptomatic at every follow-up visit . Intercurrent tick bites were reported by 45 cases (47%), and 14 (15%) developed a second episode of erythema migrans . Four other cases who were asymptomatic seroconverted between years 2 and 5 . CONCLUSION: The long-term outcome of patients with erythema migrans after antibiotic therapy was excellent, but patients from a highly endemic area in New York State remained at high risk of re-exposure to ticks and reinfection . Subjective symptoms during follow-up evaluations tended to be mild to moderate, intermittent, and associated with more symptomatic illness at the time of initial diagnosis.

Acta Pharm Hung, 2003, 73(1), 41 - 5
{Light- and temperature-induced degradation of fumagillin}; Agner G et al.; The antibiotic fumagillin with amebicidal and fungicidal effects isolated from Aspergillus fumigatus is the only presently known agent for the treatment of life threatening serious microsporidiosis occurring in patients with AIDS . Fumagillin and its degradation products were measured by HPLC at given time intervals after storage under defined conditions (temperature, relative humidity) . Significant degradation took place even in samples stored in freezer; therefore fumagillin drug substance should be stored below -60 degrees C . Light also induced a degradation process in fumagillin, thus it is proposed to be stored and transported in brown glass.

Ann Neurol, 2003 Aug, 54(2), 186 - 96
Minocycline and doxycycline are not beneficial in a model of Huntington's disease; Smith DL et al.; Huntington's Disease (HD) is an inherited neurological disorder causing movement impairment, personality changes, dementia, and premature death, for which there is currently no effective therapy . The modified tetracycline antibiotic, minocycline, has been reported to ameliorate the disease phenotype in the R6/2 mouse model of HD . Because the tetracyclines have also been reported to inhibit aggregation in other amyloid disorders, we have investigated their ability to inhibit huntingtin aggregation and further explored their efficacy in preclinical mouse trials . We show that tetracyclines are potent inhibitors of huntingtin aggregation in a hippocampal slice culture model of HD at an effective concentration of 30 microM . However, despite achieving tissue levels approaching this concentration by oral treatment of R6/2 mice with minocycline, we observed no clear difference in their behavioral abnormalities, or in aggregate load postmortem . In the light of these new data, we would advise that caution be exercised in proceeding into human clinical trials of minocycline.

Biol Reprod, 2003 Dec, 69(6), 1801 - 7 Epub 2003 Jul 30.
Tyrosine phosphorylation of HSP-90 during mammalian sperm capacitation; Ecroyd H et al.; The process of sperm capacitation is correlated with activation of a signal transduction pathway leading to protein tyrosine phosphorylation . Whereas phosphotyrosine expression is an essential prerequisite for fertilization, the proteins that are phosphorylated during capacitation have not yet been identified . In the present study, we observed that a major target of this signaling pathway is the molecular chaperone protein, heat shock protein (HSP)-86, a member of the HSP-90 family of HSPs . We used cross-immunoprecipitation experiments to confirm the tyrosine phosphorylation of HSP-86, a process that is not inhibited by the ansamycin antibiotic, geldanamycin . The general significance of these findings was confirmed by studies in which HSP-90 was also found to be tyrosine phosphorylated in human and rat spermatozoa when incubated under conditions that support capacitation . To our knowledge, these results represent the first report of a protein that undergoes tyrosine phosphorylation during mouse sperm capacitation and the first study implicating molecular chaperones in the processes by which mammalian spermatozoa gain the ability to fertilize the oocyte.

Yao Xue Xue Bao, 2003 Apr, 38(4), 250 - 4
{Potentiation and mechanism of cisplatin-induced apoptosis by lidamycin in human hepatoma BEL-7402 cells}; Liu HZ et al.; AIM: To investigate the synergetic effect and the mechanism of antitumor action of the antibiotic lidamycin in combination with cisplatin in vitro . METHODS: Cytotoxicity of the drugs was measured by clonogenic assay . Chromatin condensation was observed by co-staining with fluorescent dyes, Hoechst 33342 and propidium iodide . Apoptotic sub-G1 was detected by flow cytometry and DNA ladder was observed using agarose gel electrophoresis . Bcl-2 protein level was detected by Western blot assay . RESULTS: By using clonogenic assay, lidamycin in combination with cisplatin was found to have synergetic effects on the proliferation of human hepatoma BEL-7402 cells . The data showed that BEL-7402 cells treated with cisplatin and lidamycin in combination produced internucleosomal DNA fragmentation analysed by agarose gel electrophoresis . The results of flow cytometry showed that cisplatin and lidamycin administrated in combination showed no obvious change in G1 phase distribution compared with single treatment . However, this combination reduced the S phase arrest and reversed the reduction of G2/M phase induced by single treatment . The results also showed that there was 11.3% or 9.37% of cells undergoing apoptosis in BEL-7402 cells treated with cisplatin or lidamycin, respectively, while it showed 32.4% of apoptotic cells in combination treatment . Cisplatin, lidamycin and combination of cisplatin and lidamycin was shown to induce typical chromatin condensation in BEL-7402 cells . The study showed that 0.5 mumol.L-1 cisplatin or 1 x 10(-4) mumol.L-1 lidamycin alone decreased Bcl-2 protein level, while lidamycin in combination with cisplatin strongly inhibited expression of Bcl-2 proteins in BEL-7402 cells . CONCLUSION: The results suggest that lidamycin enhancement of cisplatin-induced apoptosis associates with decrease of Bcl-2 protein expression, which may be useful for cancer chemotherapy.

Am J Infect Control, 2003 Aug, 31(5), 266 - 72; discussion 272-3
The state of infection surveillance and control in Canadian acute care hospitals; Zoutman DE et al.; BACKGROUND: Nosocomial infections and antibiotic-resistant pathogens cause significant morbidity, mortality, and economic costs . The infection surveillance and control resources and activities in Canadian acute care hospitals had not been assessed in 20 years . METHODS: In 2000, surveys were mailed to infection control programs in all Canadian hospitals with more than 80 acute care beds . The survey was modeled after the US Study on the Efficacy of Nosocomial Infection Control instrument, with new items dealing with resistant pathogens and computerization . Surveillance and control indices were calculated . RESULTS: One hundred seventy-two of 238 (72.3%) hospitals responded . In 42.1% of hospitals, there was fewer than 1 infection control practitioner per 250 beds . Just 60% of infection control programs had physicians or doctoral professionals with infection control training who provided services . The median surveillance index was 65.6/100, and the median control index was 60.5/100 . Surgical site infection rates were reported to individual surgeons in only 36.8% of hospitals . CONCLUSIONS: There were deficits in the identified components of effective infection control programs . Greater investment in resources is needed to meet recommended standards and thereby reduce morbidity, mortality, and expense associated with nosocomial infections and antibiotic-resistant pathogens.

Am Fam Physician, 2003 Jul 1, 68(1), 135 - 40
Management of Bartholin's duct cyst and gland abscess; Omole F et al.; Bartholin's duct cysts and gland abscesses are common problems in women of reproductive age . Bartholin's glands are located bilaterally at the posterior introitus and drain through ducts that empty into the vestibule at approximately the 4 o'clock and 8 o'clock positions . These normally pea-sized glands are palpable only if the duct becomes cystic or a gland abscess develops . The differential diagnosis includes cystic and solid lesions of the vulva, such as epidermal inclusion cyst, Skene's duct cyst, hidradenoma papilliferum, and lipoma . The goal of management is to preserve the gland and its function if possible . Office-based procedures include insertion of a Word catheter for a duct cyst or gland abscess, and marsupialization of a cyst; marsupialization should not be used to treat a gland abscess . Broad-spectrum antibiotic therapy is warranted only when cellulitis is present . Excisional biopsy is reserved for use in ruling out adenocarcinoma in menopausal or perimenopausal women with an irregular, nodular Bartholin's gland mass.

Trans R Soc Trop Med Hyg, 2003 Jan-Feb, 97(1), 22 - 4
Antenatal and perinatal strategies to prevent mother-to-child transmission of HIV infection; Newell ML; Mother-to-child transmission (MTCT) is the dominant mode of acquisition of HIV infection for children . Each day an estimated 1600 children born to HIV-infected mothers become infected, 1500 of whom are in sub-Saharan Africa . Mother-to-child transmission can occur before, during and after delivery; overall rates of MTCT range from 15 to 35% . Risk factors for MTCT include maternal viral load levels, vaginal delivery, prematurity and breastfeeding . Approaches to reduce the risk of MTCT include reduction of maternal viral load through antiretroviral prophylaxis, avoidance of exposure through birth canal cleansing or elective caesarean section delivery and refraining from breastfeeding, and boosting the host immune system through nutritional supplementation or immunization . Substantial reductions in the risk of MTCT can be achieved with antiretroviral prophylaxis during pregnancy, delivery and in the neonatal period, both in settings with and without breastfeeding . Elective caesarean section independently decreases the risk, but is not a safe and feasible option in most high prevalence areas . Birth canal cleansing with chlorhexidine does not reduce the rate overall, but may be beneficial in a subgroup of women with prolonged duration of ruptured membranes . Micronutrient supplementation, including vitamin A, does not reduce MTCT of HIV, but may improve pregnancy outcome generally.

Mich Health Hosp, 2003 Jul-Aug, 39(4), 40 - 2
Back to basics: giving attention to surgical infection prevention; Conway WA Jr; When it comes to postoperative infection, there should be no argument about the business case for quality . Postoperative infection is a major cause of patient injury, mortality and health care cost . An estimated 2.6 percent of the nearly 30 million operations each year are complicated by surgical site infections, and patients with infections have twice the incidence of mortality.

Lancet, 2003 Jul 19, 362(9379), 198 - 204
Strategies for control of trachoma: observational study with quantitative PCR; Solomon AW et al.; BACKGROUND: Antibiotics are an important part of WHO's strategy to eliminate trachoma as a blinding disease by 2020 . At present, who needs to be treated is unclear . We aimed to establish the burden of ocular Chlamydia trachomatis in three trachoma-endemic communities in Tanzania and The Gambia with real-time quantitative PCR . METHODS: Conjunctival swabs were obtained at examination from 3146 individuals . Swabs were first tested by the qualitative Amplicor PCR, which is known to be highly sensitive . In positive samples, the number of copies of omp1 (a single-copy C trachomatis gene) was measured by quantitative PCR . FINDINGS: Children had the highest ocular loads of C trachomatis, although the amount of pooling in young age groups was less striking at the site with the lowest trachoma frequency . Individuals with intense inflammatory trachoma had higher loads than did those with other conjunctival signs . At the site with the highest prevalence of trachoma, 48 of 93 (52%) individuals with conjunctival scarring but no sign of active disease were positive for ocular chlamydiae . INTERPRETATION: Children younger than 10 years old, and those with intense inflammatory trachoma, probably represent the major source of ocular C trachomatis infection in endemic communities . Success of antibiotic distribution programmes could depend on these groups receiving effective treatment.

Med Microbiol Immunol (Berl), 2004 Feb, 193(1), 27 - 34 Epub 2003 Jul 22.
Experimental infection of dogs with Borrelia burgdorferi sensu stricto using Ixodes scapularis ticks artificially infected by capillary feeding; Korshus JB et al.; Specific pathogen-free dogs were experimentally infected with Borrelia burgdorferi sensu stricto using nymphal or adult female Ixodes scapularis ticks artificially infected with spirochetes by capillary feeding . The ticks were capillary fed B . burgdorferi isolate 610, previously isolated from a dog with Lyme disease and grown in BSK medium . This isolate induced clinical signs in the dogs similar to those for dogs infested with ticks naturally infected with B . burgdorferi . Adult ticks were more efficient than nymphs in transmitting spirochetes to the dogs . One of five dogs infested with nymphal ticks capillary fed B . burgdorferi was skin biopsy culture and serologically positive, and demonstrated lameness . In contrast, all five dogs infested with adult female ticks that had been capillary fed with B . burgdorferi were culture and serologically positive, with one dog developing lameness . The immunoblot profiles of dogs challenged with female ticks infected by capillary feeding (8 weeks post challenge) were similar to immunoblots (4 weeks post challenge) from dogs challenged with naturally infected females collected in the field . These studies demonstrated that B . burgdorferi cultured in BSK medium can be capillary fed to either nymphal or adult female ticks under laboratory controlled conditions for the purpose of transmitting the spirochete to dogs during the tick's blood meal . This tick infection system would be useful for a controlled and defined challenge of vaccinated and non-vaccinated dogs for proper evaluation of vaccine efficacy, which is difficult to achieve using field-collected ticks . Furthermore, this system may also be useful for investigation of the pathogenesis of Lyme disease, evaluation of the pathogenicity of new isolates of B . burgdorferi, or evaluation of antibiotic therapy.

Curr Opin Crit Care, 2003 Aug, 9(4), 300 - 5
Controversy of immunonutrition for surgical critical-illness patients; Sacks GS et al.; Specific nutrients such as arginine, glutamine, dietary nucleotides, and omega-3 fatty acids have been shown to influence infectious morbidity, antibiotic use, and hospital length of stay . The combination of these nutrients into one enteral formulation has become known as immune-enhancing diets . Consensus guidelines developed by a number of clinical investigators and published in 2001 concluded that immune-enhancing diets were beneficial in moderate to severely malnourished patients undergoing elective gastrointestinal surgery and patients sustaining severe blunt and penetrating torso trauma . The purpose of this article is to review data published between February 1, 2001, and January 31, 2003, to determine whether new studies substantiated or refuted the current recommendations for the use of immune-enhancing diets in surgical, critically injured, and critically ill patients . Results confirmed the benefits of preoperative administration of immune-enhancing diets in surgical patients but also demonstrated that postoperative administration offered no advantages . Decreased infectious complications were also observed in critically ill patients receiving immune-enhancing diets . Accumulating evidence supports the use of immune-enhancing diets in these specific patient populations.

Pancreas, 2003 Aug, 27(2), 133 - 8
Pancreatic fungal infection; Shanmugam N et al.; INTRODUCTION: There has been a steady rise in the incidence of pancreatic fungal infections . Even though fungal infections of the pancreas are not very common, they are often nosocomial . AIMS: To review pancreatic fungal infections and to compare their clinical characteristics with those of bacterial pancreatic infections, along with the causes and approaches to diagnosis and treatment . RESULTS: Because of the lack of randomized, prospective trials, standardized recommendations for use of antifungal prophylaxis would be premature . The most important aspect of prophylaxis against pancreatic fungal infection is minimizing the factors that predispose the pancreas to fungal infections . CONCLUSION: Isolation of fungal elements from necrotic pancreatic tissue and treatment of local infection are vital . Treatment of local candidal infection should be initiated with surgical necrosectomy . Systemic antifungal therapy should be started early in the course of the disease, but whether antifungal agents should be added to the prophylactic antibiotic regimens for patients with necrotizing pancreatitis remains questionable.

Am J Surg Pathol, 2003 Aug, 27(8), 1147 - 51
Histopathology of interval (delayed) appendectomy specimens: strong association with granulomatous and xanthogranulomatous appendicitis; Guo G et al.; Patients who present with a ruptured acute appendicitis are often treated with antibiotic therapy and drainage followed by a delayed or interval appendectomy . We noticed interval appendectomy specimens with granulomatous inflammation and postulated that interval appendectomy may lead to granulomatous appendicitis . To test this hypothesis, we reviewed the histopathology of all interval appendectomy specimens within a 4-year period and compared them with a control group of patients who had acute appendicitis and underwent routine acute appendectomy . All slides were randomized and reviewed blindly to assess the inflammatory patterns, with special attention given to the presence of granulomas and other Crohn-like features . Twenty-two cases of interval appendectomy were found . The interval between symptom onset and appendectomy ranged from 30 to 95 days with a mean of 58 days, whereas all 44 control patients had surgery within 72 hours of symptoms onset . Thirteen (59.1%) of the 22 interval appendectomy cases contained granulomas compared with only 3 of 44 controls (P < 0.0001) . Eight (36.4%) of the interval appendectomy cases had xanthogranulomatous inflammation compared with none in the acute appendicitis group (P < 0.0001) . A Crohn-like appearance was seen in 11 (50.0%) of the interval appendectomy cases and 1 of the controls (P < 0.0001) . Follow-up data were available in 8 of 11 cases with Crohn-like features; none developed Crohn disease during an average follow-up period of 23 months . Delayed or interval appendectomy specimens often have a characteristic inflammatory pattern that includes granulomas, xanthogranulomatous inflammation, mural fibrosis/thickening, and transmural chronic inflammation . Without the appropriate clinical history, these changes may be misinterpreted as Crohn disease.

Biochem J, 2003 Nov 15, 376(Pt 1), 245 - 52
Colicins, spermine and cephalosporins: a competitive interaction with the OmpF eyelet; Bredin J et al.; The L3 loop is an important feature of the OmpF porin structure, contributing to both channel size and electrostatic properties . Colicins A and N, spermine, and antibiotics that use OmpF to penetrate the cell, were used to investigate the structure-function relationships of L3 . Spermine was found to protect efficiently cells expressing wild-type OmpF from colicin action . Among other solutes, sugars had minor effects on colicin A activity, whereas competitions between colicin A and antibiotic fluxes were observed . Among the antibiotics tested, cefepime appeared the most efficient . Escherichia coli cells expressing various OmpF proteins mutated in the eyelet were tested for their susceptibility to colicin A, and resistant strains were found only among L3 mutants . Mutations at residues 119 and 120 were the most effective at conferring resistance to colicin A, probably due to epitope structure alteration, as revealed by a specific antipeptide . More detailed information was obtained on mutants D113A and D121A, by focusing on the kinetics of colicin A and colicin N activities through measurements of potassium efflux . D113 appeared to play an essential role for colicin A activity, whereas colicin N activity was more dependent on D121 than on D113.

Radiats Biol Radioecol, 2003 May-Jun, 43(3), 315 - 9
{Regulation of the neuronal functional state by ultra low doses of different biologically active substances . Nonspecific effect }; Terekhova SF et al.; The role of biologically active substances in ultra-low doses (10(-15)-10(-27) mol/l) is discussed from the different points of view . The most detailed analysis of neurobiological effects produced by these doses can be studied on the preparate of completely isolated molluscan neurones . In this case the possibility arises to control the first modifications of action at the electrophysiological characteristics of neuronal activity . These changes of electrical activity can be regarded as a reaction to biologically active substance . The following characteristics were controlled: the level of membrane resting potential (MP), the electroexcitable membrane and pacemaker mechanism, chemical sensitivity of somatic membrane loci to neurotransmitter acetylcholine (Ach) . Several substances were used in these experiments: two kinds of synthetic antioxidant, GABA, ethanol, serotonine, DSIP (delta-sleep inducing peptide), antibiotic ruboxil, nootrop GVS-111 . The isolated neurones were placed into the special chamber . All these substances (0.35 ml) were added single dosing into this chamber with living physiological solution in concentration 10(-15)-10(-27) mol/l . The results demonstrated that all substances had initiated the development of prolonged neurophysiological responses . The intensities of neuronal reactions didn't depend in contact period on the concentration and on the type of substance . It is suggested that these data reveal the existence of unknown modes of regulation of neuronal functional states and presence of hidden channel for information transfer and receiving . This different way of regulation is extremely important influence living organisms.

Virus Genes, 2002 Dec, 25(3), 299 - 316
Molecular anatomy of Chilo iridescent virus genome and the evolution of viral genes; Jakob NJ et al.; Chilo iridescent virus (CIV) or Insect iridescent virus 6 (IIV-6) is the type species of the genus iridovirus, a member of the Iridoviridae family . CIV is highly pathogenic for a variety of insect larvae and this implicates a possible use as a biological insecticide . CIV progeny and assembly occur in the cytoplasm of the infected cell and accumulate in the fatbody of the infected insects . Since the discovery of CIV in 1966, many attempts were made to elucidate the viral genome structure and the amino acid sequences of different viral gene products . The elucidation of the coding capacity and strategy of CIV was the first step towards understanding the underlying mechanisms of viral infection, replication and virus-host interaction . The virions contain a single linear ds DNA molecule that is circularly permuted and terminally redundant . The coding capacity of the CIV genome was determined by the analysis of the complete DNA nucleotide sequence consisting of 212,482 bp that represent 468 open reading frames encoding for polypeptides ranging from 40 to 2432 amino acid residues . The analysis of the coding capacity of the CIV genome revealed that 50% (234 ORFs) of all identified ORFs (468 ORFs) were non-overlapping . The identification of several putative viral gene products including a DNA ligase and a viral antibiotic peptide is a powerful tool for the investigation of the phylogenetic relatedness of this evolutionary and ecologically relevant eukaryotic virus.

Ann Hum Biol, 2003 Jul-Aug, 30(4), 472 - 86
Infectious disease mortality in two Outer Hebridean islands: 2 . pulmonary tuberculosis; Clegg EJ; OBJECTIVE: To examine mortality from pulmonary tuberculosis (PTB) in the Outer Hebridean islands of Harris and Barra, and to compare it with that in Scotland as a whole . DESIGN: Ages and dates of death from PTB in Harris and Barra between 1855 and 1990 were ascertained from copies of death certificates . For Scotland, annual numbers of deaths in 5-year age-groups were extracted from Annual Reports of the Registrars General . Proportionate mortality ratios (PMRs) were calculated for each population in the 1-14 and 15 or over age-groups, and the 'detrended' PMRs were subjected to spectral analysis . For this purpose the data were divided into the pre-antibiotic (1855-1950) and antibiotic/chemo-therapeutic (1951-1990) periods . RESULTS: PTB was predominantly a disease of adolescence and early adulthood, although ages at death increased towards the end of the period of study . While PMRs for Scotland decreased steadily after the mid-1870s, apart from increases during the 1940s, those for the two islands increased during the late 19th century, and did not decrease markedly until the 1930s . In the younger age-groups the pattern of mortality was similar to that of an acute infectious disease, while in the older age-group the pattern was largely endemic . Spectral analysis of pre-1951 data from both islands showed marked periodicities in mortality, mostly among the younger age-group . The introduction of effective therapy in the 1950s appeared to lengthen inter-epidemic intervals . There appeared to be no relationship in either island between mortality and socio-economic deprivation, as indicated by numbers of new poor registrations . In Harris, mortality was higher in colder and wetter years . This was not the case in Barra . CONCLUSIONS: The findings are reasonably consistent with a hypothesis that PTB was relatively uncommon in the Outer Hebrides until the later 19th century, and that it behaved epidemiologically like an acute infectious disease . This was not the case with Scotland as a whole, where the disease appeared to be largely endemic.

Anaesth Intensive Care, 2003 Jun, 31(3), 324 - 7
The dangers of trying to make ends meet: accidental intravenous administration of enteral feed; Ramsay SJ et al.; We report a case of inadvertent intravenous administration of enteral feed, a very rare but potentially life-threatening complication of enteral feeding . Bacterial contamination of feed results in a severe septic response that requires broad-spectrum antibiotic cover and aggressive organ support . The failure of measures aimed at prevention of this complication must be investigated, and practice changed to ensure that further incidents are avoided.

Rheumatol Int, 2003 Sep, 23(5), 211 - 5 Epub 2003 Jul 16.
Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes; Endresen GK; Chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) are characterised by a lack of consistent laboratory and clinical abnormalities . Although they are distinguishable as separate syndromes based on established criteria, a great number of patients are diagnosed with both . In studies using polymerase chain reaction methods, mycoplasma blood infection has been detected in about 50% of patients with CFS and/or FMS, including patients with Gulf War illnesses and symptoms that overlap with one or both syndromes . Such infection is detected in only about 10% of healthy individuals, significantly less than in patients . Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery . By means of causation and therapy, mycoplasma blood infection may permit a further subclassification of CFS and FMS . It is not clear whether mycoplasmas are associated with CFS/FMS as causal agents, cofactors, or opportunistic infections in patients with immune disturbances . Whether mycoplasma infection can be detected in about 50% of all patient populations with CFS and/or FMS is yet to be determined.

Rheumatol Int, 2004 Jul, 24(4), 221 - 6 Epub 2003 Jul 16.
Brucellar spondylitis; Bodur H et al.; We carried out a prospective analysis of 86 patients with brucellosis, and 26 (30%) cases were diagnosed as brucellar spondylitis . Two patients had cervical involvement, two thoracic, and 21 lumbosacral as seen in MRI . Four patients had epidural abscess and two had paravertebral abscess . All patients received combined antibiotic therapy for 4 to 12 months . Those with cervical involvement underwent surgical treatment because of medullar compression . Neither death nor severe sequelae were observed.

J Thorac Cardiovasc Surg, 2003 Jul, 126(1), 232 - 9
Human leukocyte antigen-DR and ABO mismatch are associated with accelerated homograft valve failure in children: implications for therapeutic interventions; Baskett RJ et al.; OBJECTIVE: This study examines the incidence and factors associated with the failure of homograft valves and identifies those factors that are modifiable . METHODS: From 1990 to 2001, 96 homograft valves were implanted in the right ventricular outflow tract of 83 children (mean age 5.1 +/- 5.6 years) . Clinical and blinded serial echocardiographic follow-up was performed on all 90 valves in the 77 survivors . RESULTS: Eighteen homograft valves were replaced as the result of pulmonary insufficiency (3), stenosis (9), or both (6) . Freedom from reoperation was 71% at 9 years (95% confidence interval, 58%-84%) . Forty-eight valves developed progressive pulmonary insufficiency of at least 2 grades, 26 valves developed transvalvular gradients of 50 mm Hg or greater, and 14 of these valves were also insufficient . The freedom from echocardiographic failure (progressive pulmonary insufficiency >or=2 grades or >or=50 mm Hg gradient) was only 27% at 5 years (95% confidence interval, 17%-37%) . In a multivariate analysis (Cox regression), use of an aortic homograft (P =.001) and short antibiotic preservation time (P =.04) were associated with reoperation . Younger age (P =.01), ABO mismatch (P =.04), and diagnosis (P =.005) were associated with echocardiographic failure . In the subanalysis of patients with human leukocyte antigen typing, age (P =.002), aortic homograft (P =.04), and human leukocyte antigen-DR mismatch (P =.03) were associated with echocardiographic valve failure . CONCLUSION: Many homografts rapidly become insufficient and require replacement . In our analysis of both reoperation and echocardiographic failure, several immunologic factors are consistently associated with homograft failure . Matching for human leukocyte antigen-DR, blood group, and avoiding short preservation times (thus minimizing antigenicity) offers the potential to extend the life of these valves.

PDA J Pharm Sci Technol, 2003 May-Jun, 57(3), 186 - 97
Helium leak test for sterility assurance of a sealed bag . II: Establishing a test method for the manufacturing process; Miyako Y et al.; To establish a simpler and more reliable method for retaining the aseptic condition of freeze-dried bulk product of a drug substance, a helium leak test method was developed . The bulk product is for the new kit system for infusion of our antibiotic product . In manufacturing the kit system, the bulk product needs to be transported outside of the aseptic area . We had to use a proper container to enclose the bulk product under aseptic conditions and establish an appropriate method for sterility assurance of the container . We decided to use a flexible aluminum laminate bag as a container and to seal it in a polyethylene bag . To detect tears or pinholes in the bag, a helium leak test was considered . As a tear model, a pinhole of known diameter was made in the aluminum laminate bag which was then filled with helium and sealed in a polyethylene bag . Helium leaking from the pinholes was measured with a helium leak detector, and leakage from a pinhole of more than 50 microm in the aluminum laminate bag could be detected . The amount of leakage was strongly affected by the pinhole diameter, and we developed a scientific approach for measuring leakage using the Poiseiulle Equation . The detection sensitivity of our method was enough to retain an aseptic condition inside the aluminum laminate bag, confirmed by the results of the process simulation test using our helium leak test . We concluded that our helium leak test was useful for sterility assurance of the bulk product sealed in the aluminum laminate bag in the manufacturing process of our kit system for infusion of our antibiotic product.

Acta Crystallogr D Biol Crystallogr, 2003 Aug, 59(Pt 8), 1507 - 9 Epub 2003 Jul 23.
Crystallization and preliminary X-ray studies on the putative dTDP sugar epimerase NovW from the novobiocin biosynthetic cluster of Streptomyces spheroides; Jakimowicz P et al.; Crystals of recombinant NovW (subunit MW = 22 289 Da), a putative dTDP sugar epimerase from Streptomyces spheroides, were grown by vapour diffusion . The protein crystallizes in space group P4(3)2(1)2, with unit-cell parameters a = b = 59.20, c = 109.23 A . Native data to a resolution of 2.0 A were collected from a single crystal at 100 K on a rotating-anode X-ray generator . Preliminary analysis of these data indicated that the asymmetric unit corresponded to a monomer, whilst dynamic light scattering (DLS) suggested that NovW was a dimer in solution . NovW is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin, which targets the bacterial enzyme DNA gyrase, and represents the first enzyme to be crystallized from this biosynthetic pathway.

Inflammation, 2003 Jun, 27(3), 147 - 59
Two pathways of activation of the superoxide-generating NADPH oxidase of phagocytes in vitro--distinctive effects of inhibitors; Sigal N et al.; The NADPH oxidase complex of phagocytes comprises a membrane-associated flavocytochrome b559, and 4 cytosolic components: p47phox, p67phox, p40phox, and the small GTPase Rac . Activation of the oxidase in vivo is the result of assembly of the cytosolic components with cytochrome b559 and is mimicked in vitro by a cell-free system consisting of membranes, p47phox, p67phox, nonprenylated or prenylated Rac, and an anionic amphiphile as activator (defined as "p47phox and amphiphile-dependent" or canonical pathway) . We reported that prenylated Rac1 is capable of activating the NADPH oxidase in vitro in the absence of p47phox and amphiphile (defined as "p47phox and amphiphile-independent" pathway) . We now demonstrate that the 2 pathways exhibit distinctive susceptibilities to inhibitors: 1) The anionic amphiphile lithium dodecyl sulfate, an activator of the canonical pathway, has the opposite effect (inhibition) on oxidase activation by prenylated Rac and p67phox; 2) GDP and, paradoxically, GTP (but not GMP, ATP, ADP, and AMP) prevent oxidase activation by the p47phox and amphiphile-independent pathway but do not affect activation by the canonical pathway; 3) The Rac-binding domain of p21-activated kinase is a potent inhibitor of activation by the p47phox and amphiphile-independent pathway while exerting a milder inhibitory effect on the canonical pathway; 4) The C-terminal polybasic Rac1 peptide 177-191 and the cationic antibiotic neomycin sulfate inhibit activation by the canonical pathway but do not affect activation by the p47phox and amphiphile-independent pathway; 5) Binding of prenylated Rac1 to membrane-mimicking phospholipid vesicles is, nevertheless, enhanced when these contain negatively charged lipids . It is proposed that preferential inhibition of oxidase activation, via the p47phox and amphiphile-independent pathway, is a reflection of interference by the inhibitors with Rac-dependent recruitment of p67phox to the membrane.

Arch Otolaryngol Head Neck Surg, 2003 Jul, 129(7), 771 - 4
Three-dose vs extended-course clindamycin prophylaxis for free-flap reconstruction of the head and neck; Carroll WR et al.; BACKGROUND: Twenty-four hours of perioperative antibiotics provides effective prophylaxis for most head and neck cancer resections . Many reconstructive surgeons have been hesitant to apply this standard to free-flap reconstruction of the head and neck . This prospective clinical trial compared short-course and long-course clindamycin prophylaxis for wound infection in patients with head and neck cancer undergoing free-flap reconstruction . METHODS: Seventy-four patients were randomized to receive short-course (3 doses) or long-course (15 doses) clindamycin perioperatively . Wound infections, fistulas, and other postoperative complications were documented by faculty surgeons who were blinded as to treatment group . RESULTS: The differences in wound infections and other complications were statistically insignificant . No other independent predictors of wound complications emerged in this series of patients . CONCLUSIONS: Short-course clindamycin is as effective as long-course clindamycin in preventing wound infections after free-flap surgery for head and neck ablative defects.

Int J Gynaecol Obstet, 2003 Aug, 82(2), 167 - 72
Preterm premature rupture of membranes and neonatal outcome prior to 34 weeks of gestation; Tanir HM et al.; OBJECTIVES: To investigate the impact of preterm premature rupture of membranes on neonatal outcome . METHODS: A retrospective study was conducted among singleton pregnancies with or without intact amniochorional membranes . The impact of maternal age, gestational age at birth, 1- and 5-min Apgar scores, birthweight, presence of meconium, use of tocolytics, corticosteroids and antibiotics, mode of delivery, umbilical artery pH, histologic presence of chorioamnionitis, and state of the membranes were analyzed in relation to neonatal outcome . Neonatal outcomes were categorized into: none, presence of respiratory distress syndrome, early neonatal sepsis, neonatal death, and days at neonatal intensive care unit . RESULTS: A total of 180 preterm deliveries with ruptured (n=80) and intact membranes (n=100) constituted the study group (group 1) and the control group (group 2), respectively . Compared with group 2, there were more cases in group 1 of maternal antibiotic use (P<0.001), short-term tocolysis (P=0.03), and histologic chorioamnionitis (P<0.001) . Multiple logistic regression analysis showed that gestational age at delivery (P=0.009), 1-min Apgar score (P=0.013), and umbilical artery pH (P=0.05) were the independent factors affecting neonatal outcome . CONCLUSIONS: Neonatal outcome was mainly affected by prematurity rather than by preterm premature rupture of membranes.

J Heart Lung Transplant, 2003 Jul, 22(7), 754 - 63
Impact of prophylaxis with cytogam alone on the incidence of CMV viremia in CMV-seropositive lung transplant recipients; Kruger RM et al.; BACKGROUND: Cytomegalovirus (CMV) infection remains a serious problem after lung transplantation . The purpose of this study was to evaluate the efficacy of CytoGam, a CMV hyperimmune globulin (CMV-IGIV), as CMV prophylaxis after lung transplantation . METHODS: This prospective, randomized, open-label study compared prophylaxis with CMV-IGIV and no prophylaxis in 44 CMV-seropositive lung transplant recipients . The primary end-point was development of CMV viremia during the first year after transplantation . RESULTS: Cytomegalovirus viremia was detected in 13 of 22 recipients without prophylaxis and in 16 of 22 recipients with CMV-IGIV prophylaxis (p = 0.19) . Cytomegalovirus pneumonitis developed in 8 controls vs in 11 CMV-IGIV recipients (p = 0.54) . We found no significant difference between the groups in the incidence of positive shell vial assays (6.8% +/- 6.5% without vs 11.2% +/- 10.1% with prophylaxis, p = 0.09) or in the attack rate of CMV pneumonitis (0.41 +/- 0.59 episodes/patient without vs 0.86 +/- 0.99 episodes/patient with prophylaxis, p = 0.07) . Similarly, no difference was apparent in the time to onset of CMV viremia, to detection of CMV DNA in peripheral blood leukocytes by polymerase chain reaction, or to development of CMV pneumonitis . The incidence of acute rejection and bronchiolitis obliterans syndrome and the survival rate during the first post-transplant year did not differ between the groups . CONCLUSIONS: Prophylaxis with CMV-IGIV alone did not decrease CMV viremia or pneumonitis, did not decrease the incidence of acute rejection or bronchiolitis obliterans syndrome, and did not affect 1-year survival of CMV-seropositive lung transplant recipients at our center.

Poult Sci, 2003 Jul, 82(7), 1205 - 10
Penetration of surface-inoculated bacteria as a result of electrically generated hydrodynamic shock wave treatment of boneless skinless chicken breasts; Lorca TA et al.; The top surface of boneless skinless chicken breasts was inoculated with either green fluorescent protein (GFP)-labeled Escherichia coli (E . coli-GFP) or rifampicin-resistant E . coli (E . coli-Rif) and subjected to electrically generated hydrodynamic shock wave treatment (HVADH) . Cryostat sampling in concert with laser scanning confocal microscopy or plating onto antibiotic selective agar was used to determine if HVADH treatment resulted in the movement of the inoculated bacteria from the outer inoculated surface to the interior of intact boneless skinless chicken breasts . In HVADH-treated boneless skinless chicken breasts, marker bacteria were detected within the first 200 microm below the inoculated surface, 50 to 100 microm beyond the depth of untreated surface inoculated boneless skinless chicken breasts . The exact depth at which the marker bacteria were found was dependent on the cryostat sampling distance used . These results suggest that HVADH treatments affect the movement of surface bacteria.

J Basic Microbiol, 2003, 43(4), 301 - 11
Evaluation of combined 16S rDNA and strb1 gene targeted PCR to identify and detect streptomycin-producing Streptomyces; Gharaibeh R et al.; In this study, two designed primers were evaluated to identify soil Streptomyces and to detect streptomycin production by strb1 targeted PCR . Potential Streptomyces-specific signatures were identified in their 16S rDNA sequences in regions located around nucleotide positions 576 and 995 . Primer pair RI7/RI8 derived from these regions was investigated for its specificity in detecting and identifying Streptomyces isolates by PCR assays using DNA from pure cultures . The constructed primer pair showed high specificity in detecting and identifying Streptomyces type strains as well as soil isolates . Streptomycin-producers were detected by PCR assays through the selective amplification of streptomycin biosynthetic gene (strb1) . Results suggest that PCR assay facilitates the differential identification of Streptomyces-specific antibiotic producers and a resident population of Streptomyces in Jordan with the capacity of streptomycin-production is present.

Eur J Paediatr Dent, 2002 Sep, 3(3), 133 - 40
Chemical and pharmacological shaping of necrotic primary teeth; Ballesio I et al.; AIM: The object of this study was the evaluation of the success rate of endodontic treatment of primary teeth with necrotic pulps performed through a partial pulpectomy and a chemical shaping . MATERIALS AND METHODS: The study was conducted on 50 necrotic primary molars, with an oral fistula and a clinical and radiographical positive diagnosis . On each tooth the endodontic treatment was performed through mechanical strumentation for only 2-3 mm beyond the orifices of the canals and copious alternate irrigation with 10vol H(2)O(2) and 3% NaOCl (chemical shaping) . After the pharmacological shaping the canals were filled with a slurry mix of powdered macrolide antibiotic (josamicina) and glycerine (or anaesthetic solution) . At the second visit the same procedure was either repeated, if an oral fistula was still present, or the canals were sealed with a small amount of josamicina and glycerine paste and zinc oxide eugenol to a working length . RESULTS: The overall success rate, considering the first two teeth that were extracted as inappropriate case selection, was 45 out of the original 48 or 93% . While considering all the teeth treated the success rate was 45 out of 50, or 90%.

J Org Chem, 2003 Jul 25, 68(15), 5838 - 51
Versatile and facile synthesis of diverse semisynthetic tetracycline derivatives via Pd-catalyzed reactions; Nelson ML et al.; A diverse collection of tetracycline derivatives has been synthesized utilizing Heck, Suzuki, and other palladium-coupling reactions via tetracycline arenediazonium and iodoarene salts . Large numbers of tetracyclines are now possible via these reactions, including numerous upper periphery derivatives of doxycycline, minocycline, sancycline, and methacycline modified at positions C7, C9, and C6-C13 on the tetracycline naphthacene ring . Application of palladium-coupling reactions to the tetracyclines has yielded new tetracycline classes with differing structural attributes, greatly increasing the structural diversity of this family of antibiotics, one of the last of the early antibiotic families to be expanded by organic and medicinal chemistry.

J Org Chem, 2003 Jul 25, 68(15), 5819 - 25
A multistage, one-pot procedure mediated by a single catalyst: a new approach to the catalytic asymmetric synthesis of beta-amino acids; Hafez AM et al.; A catalytic asymmetric procedure for the preparation of beta-amino acids (specifically beta-substituted aspartic acid derivatives) is reported . The cinchona alkaloid catalyst benzoylquinine (BQ) mediates up to five distinct steps of a reaction pathway, all in one reaction vessel . The products of this reaction, highly optically enriched beta-substituted aspartic acid derivatives, were prepared from N-acyl-alpha-chloroglycine esters and acid chlorides in the presence of the catalyst . This approach was also amenable to the synthesis of small polypeptides containing beta-substituted aspartic acid units, including a non-natural fragment of the antibiotic lysobactin . The addition of Lewis acids to this system was found to accelerate the rate of specific steps in the reaction pathway . Mechanistic aspects of this reaction, such as imine formation and Lewis acid chelation to the beta-lactam intermediate, were investigated through comparison of IR, NMR, and other physical data.

Org Lett, 2003 Jul 24, 5(15), 2683 - 6
Total synthesis of (+/-)-spiroxin C; Miyashita K et al.; {reaction: see text} The first total synthesis of a marine-derived potent antitumor antibiotic, (+/-)-spiroxin C, was achieved via a TBAF-activated Suzuki-Miyaura cross-coupling reaction as a key step, which was also shown to be useful for the synthesis of sterically hindered binaphthyl derivatives.

J Chemother, 2003 Jun, 15(3), 266 - 74
Drug interactions of paclitaxel metabolism in human liver microsomes; Bun SS et al.; The human liver metabolism of paclitaxel (Taxol), an anticancer drug, leads to three metabolites: 6alpha-hydroxypaclitaxel, 3'-p-hydroxypaclitaxel and 6alpha,3'-p-dihydroxypaclitaxel . The inter-individual variability of paclitaxel metabolism was investigated first in vitro using 22 human liver microsomes . Three metabolites have been detected by HPLC . This preliminary work revealed marked inter-individual differences in paclitaxel metabolism . The amount of major metabolite 6alpha-hydroxypaclitaxel formed varied 16-fold (0.7 to 11.5 nmol/mg/h) . We next studied the effect of 29 compounds (antineoplastics, antiemetics, histamine-2 receptor antagonist, antalgics, antifungals, antivirals, psychotropics, antibiotic, corticoid, antiarrhythmic, calcium channel blocker) on paclitaxel metabolism in human liver microsomes . Among the compounds studied, quercetin, antifungal drugs such as ketoconazole and miconazole, and the antineoplastic drug doxorubicin inhibited formation of 6alpha-hydroxypaclitaxel . Dixon plots indicated that quercetin and doxorubicin inhibited 6alpha-hydroxypaclitaxel formation through a competitive mechanism with a Ki of 10.1 microM and 64.8 microM, respectively . The inhibition of this metabolite by ketoconazole was through a noncompetitive mechanism with a Ki of 11.8 microM . Our data thus suggest that special attention should be paid when these drugs are combined in clinical practice.

Chronobiol Int, 2003 May, 20(3), 463 - 71
Dosing-time-dependent variation in biliary excretion of flomoxef in rats; Hishikawa S et al.; We previously reported that the biliary excretion of flomoxef, an oxacephem antibiotic, was greater after dosing at 21:00 than at 09:00 h in diurnally active human subjects . The present study was undertaken to examine whether the biliary excretion of flomoxef is also dependent on its dosing time in rats . Adult male Wistar rats were housed under light on at 07:00 h and off at 19:00 h . Bile fluid was completely drained through a polyethylene catheter from conscious animals . Flomoxef (20 mg/kg) was injected into the tail vein at 09:00 or 21:00 h by a cross-over design, and drained bile fluid was collected for 8 h after each dosing . The maximum concentration of biliary flomoxef was significantly greater and its total excretion tended to be greater after dosing at 09:00 than 21:00 h . These results suggest the biliary excretion of flomoxef is enhanced after dosing at the beginning of the rest period in rats, as it is in humans.

Orbit, 2003 Sep, 22(3), 171 - 5
Primary lacrimal sac B-cell immunoblastic lymphoma simulating an acute dacryocystitis; de Palma P et al.; The case of a 72-year-old woman with diffuse large B-cell lymphoma of the lacrimal sac is reported . The patient was evaluated for the first time in our department for tearing of the right eye . One month later, a slightly aching mass appeared over the right lacrimal sac . An acute infectious etiology was suspected and antibiotic therapy was given . When she finally presented with a rapidly growing lesion, she underwent echography and computed tomography followed by incisional biopsy . Results of histopathologic and immunohistochemical evaluation showed a primary, diffuse, large B-cell non-Hodgkin lymphoma of the lacrimal sac . This case demonstrates how difficult the clinical diagnosis of tumors of the lacrimal sac may be in the early stages . The clinical signs, usually aspecific, may be misleading and the diagnosis delayed.

Drug Metab Dispos, 2003 Aug, 31(8), 983 - 5
Identification of a rare sulfonic acid metabolite of andrographolide in rats; He X et al.; Andrographolide is widely used in clinic as an anti-inflammatory and antibiotic drug . In this paper, the metabolites of andrographolide in rats after single oral doses of 120 mg/kg were investigated . The structures of the metabolites were elucidated by high-resolution mass spectra, NMR spectroscopy including 1H NMR, 13C NMR, and two-dimensional NMR, through comparison to a synthetic standard . The main metabolite of andrographolide in rats was 14-deoxy-12(R)-sulfo andrographolide . In the proposed mechanism, the beta-carbon of alpha, beta-unsaturated carbonyl was attacked by sulfonic acid, to form the sulfonate compound . This was a rare metabolic reaction . It may be the main metabolic pathway of andrographolide in rats . The polarity of the sulfonate metabolite increased greatly and could be easily eliminated from body.

Ophthalmology, 2003 Jul, 110(7), 1430 - 2
Infection after blepharoplasty with and without carbon dioxide laser resurfacing; Carter SR et al.; PURPOSE: To determine the rate of infection in patients who underwent blepharoplasty with and without carbon dioxide laser resurfacing . DESIGN: A retrospective, nonrandomized, consecutive case series . PARTICIPANTS: Eighteen hundred sixty-one patients who underwent upper or lower blepharoplasty, with or without carbon dioxide laser resurfacing . METHODS: Charts of patients who underwent blepharoplasty, with or without laser resurfacing, were analyzed for the presence of postoperative infection, method of treatment, and possible sequelae . MAIN OUTCOME MEASURES: The rate of infection (%) was determined for each group of patients . RESULTS: Infection occurred in 0.2% of patients who underwent blepharoplasty without laser resurfacing and 0.4% of patients who had adjunctive laser resurfacing . No permanent functional or cosmetic sequelae resulted from the episodes of infection . CONCLUSIONS: Infection after blepharoplasty without laser resurfacing is uncommon, indicating that topical antibiotic ointment prophylaxis is a sufficient postoperative regimen . The use of adjunctive laser resurfacing may increase the infection rate slightly.

J Emerg Med, 2003 Jul, 25(1), 45 - 9
Otomastoiditis-related facial nerve palsy; Helms D et al.; A 9-year-old girl with persistent otitis media, despite antibiotic therapy developed a facial nerve palsy . Computed tomography (CT) scan revealed ipsilateral mastoiditis, prompting admission for intravenous antibiotic and steroid therapies . Acute mastoiditis, uncommon in the post-antibiotic era, is usually diagnosed on physical examination findings, but two variants, masked mastoiditis or silent mastoiditis, may be difficult to appreciate clinically . Patients who present with facial nerve palsy in the setting of persistent otitis media should undergo CT scan for evaluation of intracerebral or extracerebral pathology, including mastoiditis . Failure to identify associated concomitant pathology may result in treatment failure or persistent neurological deficit.

Am J Rhinol, 2003 May-Jun, 17(3), 139 - 42
Cost analysis in the diagnosis of chronic rhinosinusitis; Stankiewicz JA et al.; BACKGROUND: The present treatment regimen for a diagnosis of chronic rhinosinusitis involves a prolonged course of antibiotic therapy along with other adjunctive therapy . The decision to start treatment is made after diagnosis of chronic rhinosinusitis, which is based on subjective symptoms . The working hypothesis of this study is that the diagnosis based on subjective symptoms is inaccurate, leading to inappropriate antibiotic therapy and unnecessary health care expense . METHODS: One hundred patients were evaluated prospectively to determine which patients qualified for this study . Seventy-eight patients satisfied current criteria for a diagnosis of rhinosinusitis . RESULTS: Fifty-three percent (41 patients) of the 78 patients did not have a diagnosis of chronic sinusitis based on same-day computed tomography (CT) scanning . A charge analysis comparing treatment after diagnosis with medical therapy alone and CT scan for failures versus CT scanning with medical treatment for positive scans was performed . Although the most economical method of treatment was initiating medical therapy, it was also the least sensitive and specific in that 52% of patients didn't require the treatment . Endoscopy and/or CT screening with medical therapy were much better at appropriate diagnosis and targeted therapy but charge analysis indicated a much higher cost . CONCLUSION: Presently, the current subjective diagnostic paradigm for chronic rhinosinusitis is most cost-effective but least accurate . Objective evaluations (endoscopy and CT scanning) to aid in diagnosis are more accurate but more costly . Where cost constraints are important, careful considerations of alternatives are important.

Ann Rheum Dis, 2003 Aug, 62(8), 778 - 80
Alopecia areata and relapsing polychondritis or mosaic autoimmunity? The first experience of co-trimoxazole treatment; Rozin AP et al.; A 13 year old girl presented with auricular chondritis and recurrent episodes of unexplained chest pain, arthritis, bronchitis, conjunctivitis, prolonged steroid resistant alopecia areata, and a history of recurrent tonsillitis . Both the mosaic of autoimmunity and relapsing polychondritis were considered in the differential diagnosis . The patient was successfully treated with co-trimoxazole . The significance of co-trimoxazole, which is an antibiotic and an immunomodulatory drug, in the treatment of autoimmune disease is discussed.

Ann N Y Acad Sci, 2003 Jun, 990, 444 - 9
Wolbachia in the inflammatory pathogenesis of human filariasis; Taylor MJ; Filarial nematodes cause some of the most debilitating diseases in tropical medicine . Recent studies, however, have implicated the parasites' endosymbiotic Wolbachia bacteria, rather than the nematode, as the cause of inflammatory-mediated filarial disease . Soluble extracts of a variety of filarial species stimulate innate inflammatory responses, which are absent or reduced when using extracts derived from species either devoid of bacteria, or those cleared of bacteria by antibiotics . Characterization of the molecular nature of the bacterial derived inflammatory stimulus points toward an endotoxin-like activity that is dependent on the pattern recognition receptors CD14 and TLR4 and can be inhibited by lipid A antagonists . TLR4 dependent inflammation has been shown to occur in the systemic inflammatory adverse reaction to Brugia malayi following anti-filarial chemotherapy and in the development of neutrophil-mediated ocular inflammation in a mouse model of river blindness . The development of acute and severe inflammatory responses in people infected with Brugia malayi and Onchocerca volvulus is associated with the release of Wolbachia into the blood following death or damage of the worms after anti-filarial chemotherapy . Together these studies suggest that Wolbachia are the principal cause of acute inflammatory filarial disease . Accumulated exposure to acute episodes of inflammation may also underlie the development of chronic filarial pathology . The use of antibiotic therapy to target Wolbachia of filarial parasites may therefore provide a means to prevent the development of filarial pathology.

Ann N Y Acad Sci, 2003 Jun, 990, 295 - 301
Physician knowledge of the diagnosis and management of Rocky Mountain spotted fever: Mississippi, 2002; O'Reilly M et al.; Rocky Mountain spotted fever (RMSF), a tick-borne illness that has its highest incidence in the south central and southeastern United States, is often a diagnostic challenge, as patients frequently present with nonspecific symptoms during the early stages of illness . RMSF has a high case fatality rate among untreated individuals, and the median time from onset of symptoms to death is only eight days, making early recognition and treatment of RMSF crucial . In two Mississippi public health districts, 148 primary care physicians were randomly selected and mailed surveys regarding RMSF diagnosis, treatment, and prevention . Eighty-four of the 148 (57%) physicians responded . Responses from different specialties and different health districts were compared using chi square statistics . Almost all (99%) physicians correctly identified doxycycline as the antibiotic agent of choice for treating adults and adolescents . However, only 21% of family practice physicians, and 25% of emergency medicine physicians correctly identified the antibiotic of choice for treating children with RMSF . Twenty-three percent of physicians responded that waiting for the development of a rash before prescribing antibiotics is an appropriate treatment strategy . The current standard of care-doxycycline as the agent of choice among children 8 years of age or younger with suspected RMSF-has not been effectively communicated to all physicians caring for children . Also, many physicians are not familiar with the rationale underlying initiation of antibiotic therapy prior to the development of rash in patients with suspected RMSF . Continuing education efforts should focus on antibiotic selection in pediatric patients and initiation of therapy prior to the onset of rash in appropriate patients.

Biochemistry, 2003 Jul 22, 42(28), 8423 - 33
Solution structure and dynamics of oxytetracycline polyketide synthase acyl carrier protein from Streptomyces rimosus; Findlow SC et al.; Type II polyketide synthases (PKSs) utilize a dedicated and essential acyl carrier protein (ACP) in the biosynthesis of a specific polyketide product . As part of our ongoing studies into the mechanisms and control of polyketide biosynthesis, we report the second structure of a polyketide synthase ACP . In this work, multidimensional, heteronuclear NMR was employed to investigate the structure and dynamics of the ACP involved in the biosynthesis of the commonly prescribed polyketide antibiotic, oxytetracycline (otc) . An ensemble of 28 structures of the 95 amino acid otc ACP (9916Da) was computed by simulated annealing with the inclusion of 1132 experimental restraints . Atomic RMSDs about the mean structure for all 28 models is 0.66 A for backbone atoms, 1.15 A for all heavy atoms (both values calculated for the folded part of the protein (residues 3-80)), and 0.41 A for backbone atoms within secondary structure . Otc ACP adopts the typical right-handed, four-helix fold of currently known ACPs but with the addition of a 13-residue flexible C-terminus . A comparison of the global folds of all structurally characterized ACPs is described, illustrating that PKS ACPs show clear differences as well as similarities to FAS ACPs . (15)N relaxation experiments for the protein backbone also reveal that the long loop between helices I and II is flexible and helix II, a proposed site of protein-protein interactions, shows conformational exchange . The helices of the ACP form a rigid scaffold for the protein, but these are interspersed with an unusual proportion of flexible linker regions.

HNO, 2003 Jun, 51(6), 486 - 91
{Pyoderma gangrenosum and orbital pseudotumor}; Welzel C et al.; Pyoderma gangrenosum belongs to the chronic, neutrophilic and necrotic dermatoses . These very painful, inflammable and purulent skin-ulcers often arise after injury or surgical intervention . About half of the patients suffer from systemic disease, for example hematological, gastrointestinal or rheumatic diseases . Our report includes a 77-year-old female with a multilocular emergence of pyoderma gangrenosum following surgery for an orbital pseudotumor . An additional lesion was detected on her anterior neck . Because the possibility of wound-infection was suspected, the lesion was treated locally and with a systemic antibiotic therapy . After this treatment the condition of the wound deteriorated . Upon dermatological examination, pyoderma gangrenosum was identified and a immunosuppressive therapy with corticosteroids and cyclosporin was initiated . As a result of this treatment the lesion healed slowly--with the formation of typical, atrophic and reticular scars . A connection between the pyoderma gangrenosum and the orbital pseudotumor can, on the basis of similar clinical and structural characteristics, not be excluded . A related disease was not diagnosed in this patient . Recurrence can be predicted in patients who have had skin injuries, therefore strict observation is required.

Clin Microbiol Rev, 2003 Jul, 16(3), 415 - 29
Reprogramming the host response in bacterial meningitis: how best to improve outcome?
van der Flier M, Geelen SP, Kimpen JL, Hoepelman IM, Tuomanen EI.
Despite effective antibiotic therapy, bacterial meningitis is still associated with high morbidity and mortality in both children and adults . Animal studies have shown that the host inflammatory response induced by bacterial products in the subarachnoid space is associated with central nervous system injury . Thus, attenuation of inflammation early in the disease process might improve the outcome . The feasibility of such an approach is demonstrated by the reduction in neurologic sequelae achieved with adjuvant dexamethasone therapy . Increased understanding of the pathways of inflammation and neuronal damage has suggested rational new targets to modulate the host response in bacterial meningitis, but prediction of which agents would be optimal has been difficult . This review compares the future promise of benefit from the use of diverse adjuvant agents . It appears unlikely that inhibition of a single proinflammatory mediator will prove useful in clinical practice, but several avenues to reprogram a wider array of mediators simultaneously are encouraging . Particularly promising are efforts to adjust combinations of cytokines, to inhibit neuronal apoptosis and to enhance brain repair.

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2003 Jul, 15(7), 426 - 8
{Clinic analysis of multiple interventional ways treating 37 cases with acute necrotic pancreatitis}; Liang C; OBJECTIVE: To investigate the effects of multiple interventional ways to treat acute necrotic pancreatitis (ANP) . METHODS: To study retrospectively different treatments for ANP, 37 patients were injected through pancreatic artery with octreotide, antibiotic dexamethasone, procaine, while 30 controls with traditional way . RESULTS: For patients subjected with intervention, abdomen pain was released, amylopsin was normal, treating time was shorter than that of controls (P<0.05 or P<0.01); the incidence of complications of intervention and control were 19.44% and 41.93% respectively, and the mortality were 2.70% and 16.67% (all P<0.05) . CONCLUSION: Interventional treatment for ANP is more effective than the traditional treatment.

J Ind Microbiol Biotechnol, 2003 Aug, 30(8), 523 - 9 Epub 2003 Jul 10.
Evidence from proteomics that some of the enzymes of actinorhodin biosynthesis have more than one form and may occupy distinctive cellular locations; Hesketh A et al.; An important attribute of proteome analysis carried out with the aid of two-dimensional gel electrophoresis is that post-translational modifications of proteins can often be revealed . Large-scale proteomic analysis of Streptomyces coelicolor A3(2) has been made possible with the availability of its genome sequence . Here, we bring together observations on the proteins specifically associated with biosynthesis of the isochromanequinone polyketide antibiotic actinorhodin . The predicted products of 14 of the genes annotated as belonging to the act gene cluster were detected . They were generally present only in stationary phase cultures . Plausible explanations are presented for the absence of the other nine . For six of the gene products detected, there was evidence of either specific processing or covalent modification; in the case of the pyran ring closure enzyme ActVI-ORF3, the cleavage of the N-terminal 31 or 34 amino acids was previously shown to be associated with an extracytoplasmic location for the mature gene product . These observations may have implications for the regulation of actinorhodin biosynthesis, and for biochemical studies of artificially expressed Act proteins.

Intensive Care Med, 2003 Sep, 29(9), 1528 - 34 Epub 2003 Jul 10.
Pharmacokinetics and pharmacodynamics of sequential intravenous and subcutaneous teicoplanin in critically ill patients without vasopressors; Barbot A et al.; OBJECTIVE: To compare the pharmacokinetic parameters of sequential intravenous and subcutaneous teicoplanin in the plasma of surgical intensive care unit patients . DESIGN AND SETTING: Prospective, randomized, crossover study in the surgical ICU of a university hospital . PATIENTS: Twelve patients with a suspected nosocomial infection, a serum albumin level higher than 10 g/l, body mass index less than 28 kg/m(2), and estimated creatinine clearance higher than 70 ml/min . INTERVENTIONS: Teicoplanin was first administered intravenously as a loading dose of 6 mg/kg per 12 h for 48 h and then continued at a daily dose of 6 mg/kg . On the fourth day patients were randomized in two groups according to the order of the pharmacokinetic studies . MEASUREMENTS AND RESULTS: Serial plasma samples were obtained to measure teicoplanin levels . Compared with a 30-min intravenous infusion the peak concentration of teicoplanin after a 30-min subcutaneous administration occurred later (median 7 h, range 5-18) and was lower (16 micro g/ml, 9-31; vs . 73, 53-106) . Despite large and unpredictable interindividual differences no significant differences between subcutaneous and intravenous administration were observed in: trough antibiotic concentrations (10 micro g/ml, 6-24; vs . 9, 5-30), the area under the teicoplanin plasma concentration vs . time curves from 0 to 24 h (AUC(0-24h); 309 micro g/ml per minute, 180-640; vs . 369, 171-955), the proportion of the dosing interval during which the plasma teicoplanin concentration exceeded 10 micro g/ml (96%, 0-100%; vs . 79%, 13-100%), and the ratio of AUC(0-24h) to 10 (77, 45-160; vs . 92, 43-239) . CONCLUSIONS: In critically ill patients without vasopressors a switch to the subcutaneous teicoplanin after an initial intravenous therapy seems to give comparable pharmacodynamic indexes of therapeutic success.

Microbiology, 2003 Jul, 149(Pt 7), 1633 - 45
Cloning, sequencing and heterologous expression of the medermycin biosynthetic gene cluster of Streptomyces sp . AM-7161: towards comparative analysis of the benzoisochromanequinone gene clusters; Ichinose K et al.; Medermycin is a Streptomyces aromatic C-glycoside antibiotic classified in the benzoisochromanequinones (BIQs), which presents several interesting biosynthetic problems concerning polyketide synthase (PKS), post-PKS tailoring and deoxysugar pathways . The biosynthetic gene cluster for medermycin (the med cluster) was cloned from Streptomyces sp . AM-7161 . Completeness of the clone was proved by the heterologous expression of a cosmid carrying the entire med cluster in Streptomyces coelicolor CH999 to produce medermycin . The DNA sequence of the cosmid (36 202 bp) revealed 34 complete ORFs, with an incomplete ORF at either end . Functional assignment of the deduced products was made for PKS and biosynthetically related enzymes, tailoring steps including strereochemical control, oxidation, angolosamine pathway, C-glycosylation, and regulation . The med cluster was estimated to be about 30 kb long, covering 29 ORFs . An unusual characteristic of the cluster is the disconnected organization of the minimal PKS genes: med-ORF23 encoding the acyl carrier protein is 20 kb apart from med-ORF1 and med-ORF2 for the two ketosynthase components . Secondly, the six genes (med-ORF14, 15, 16, 17, 18 and 20) for the biosynthesis of the deoxysugar, angolosamine, are all contiguous . Finally, the finding of a glycosyltransferase gene, med-ORF8, suggests a possible involvement of conventional C-glycosylation in medermycin biosynthesis . Comparison among the three complete BIQ gene clusters - med and those for actinorhodin (act) and granaticin (gra) - revealed some common genes whose deduced functions are unavailable from database searches (the 'unknowns') . An example is med-ORF5, a homologue of actVI-ORF3 and gra-ORF18, which was highlighted by a recent proteomic analysis of S . coelicolor A3(2).

Chest, 2003 Jul, 124(1), 275 - 84
New choices for central venous catheters: potential financial implications; Shorr AF et al.; OBJECTIVE: To determine the cost-effectiveness of the newer antiseptic and antibiotic-impregnated central venous catheters (CVCs) relative to uncoated CVCs and to each other . DESIGN: Decision model analysis of the cost and efficacy of CVCs coated with either chlorhexidine silver sulfadiazine (CSS) or rifampin-minocycline (RM) at preventing catheter-related bloodstream infections (CRBSIs) . The primary outcome is the incremental cost (or savings) to prevent one additional CRBSI . Model estimates are derived from prospective trials of the CSS and RM CVCs and from other studies describing the costs of CRBSIs . Setting and patients: Hypothetical cohort of 1,000 patients requiring placement of a CVC . INTERVENTIONS: In the model, patients were managed with either an uncoated CVC, CSS CVC, or RM CVC . Measurements and main results: The incremental cost-effectiveness of the treated CVCs was calculated as the savings resulting from CRBSIs averted less the additional costs of the newer devices . Sensitivity analysis of the effect of the major clinical inputs was performed . For the base case analysis, we assumed the incidence of CRBSIs was 3.3% with traditional catheters and that the CSS and RM CVC conferred a relative risk reduction for the development of CRBSIs of 60% and 85%, respectively . Despite their significantly higher cost than older catheters, both novel CVCs yield significant savings . Employing either of the treated CVCs saves approximately $10,000 per CRBSI prevented (relative to standard catheters) . Comparing the RM CVC to the CSS CVC revealed the RM product to be economically superior, saving nearly $9,600 per CRBSI averted and $81 per patient in the cohort . For sensitivity analysis, we adjusted all model variables by 50% individually and then simultaneously . This demonstrated the model to be most sensitive to the cost of a CRBSI; however, with all inputs skewed by 50% against both the CSS CVC and the RM CVC, these devices remained economically attractive . Under this scenario, use of either treated device was less costly . CONCLUSIONS: Utilization of antiseptic and antibiotic-impregnated CVCs represent an attractive alternative for the prevention of CRBSIs and may lead to significant savings . Of the two newer, coated devices, the RM CVC performs better financially . These observations hold over a range of estimates for our model inputs.

Clin Diagn Lab Immunol, 2003 Jul, 10(4), 616 - 21
Efficiency of a pneumococcal opsonophagocytic killing assay improved by multiplexing and by coloring colonies; Kim KH et al.; For evaluating pneumococcal vaccines, the opsonophagocytic killing assay (OPKA) is useful as a supplement to the pneumococcal antibody enzyme-linked immunosorbent assay (ELISA) . However, evaluations of pneumococcal vaccines require the determination of antibody responses to 7 to 11 serotypes, and the OPKA is tedious to perform and requires more serum than the ELISA . Consequently, the OPKA is infrequently used for evaluating pneumococcal vaccines . To overcome these limitations, we have developed a simple multiplexed (double-serotype) OPKA by using antibiotic-resistant pneumococci for nine serotypes . Serotype 6B, 9V, 19A, and 23F strains were made streptomycin resistant, and serotype 4, 6A, 14, 18C, and 19F strains were made optochin resistant . The multiplexed OPKA was the same as the single-serotype OPKA except for two changes . First, the target bacteria were a mixture of one streptomycin-resistant strain and one optochin-resistant strain . Second, the surviving bacteria of each serotype were enumerated by plating on Todd-Hewitt agar plates with yeast extract and an agar overlay containing the appropriate antibiotics and 2,3,5-triphenyl tetrazolium chloride . The performance of the multiplexed OPKA was evaluated by analyzing 28 serum samples from adults immunized with a 23-valent polysaccharide vaccine by using the single-serotype OPKA and the multiplexed OPKA . The multiplexed OPKA was specific for the desired serotypes . The multiplexed and conventional OPKAs had comparable assay sensitivities and produced results that were highly correlated (r(2) values ranging from 0.92 to 0.98) for all nine serotypes . A simple modification of the conventional OPKA produces a multiplexed assay that greatly reduces effort, reagents, and the necessary amount of serum.

J AOAC Int, 2003 May-Jun, 86(3), 515 - 20
Determination of florfenicol amine in channel catfish muscle by liquid chromatography; Wrzesinski CL et al.; A method for quantifying florfenicol amine (FFA) in channel catfish muscle was validated according to U.S . Food and Drug Administration guidelines . FFA is the proposed marker residue for the veterinary antibiotic florfenicol in catfish muscle for regulatory surveillance purposes . The method includes acid hydrolysis followed by sample cleanup with ethyl acetate extraction, basification, solid-phase extraction, and quantitation by liquid chromatography with UV detection . The assay was validated at 5 concentrations in the range of 0.075-35 microg/g muscle . The overall mean recovery of FFA from fish tissues fortified at these concentrations ranged from 85.7 to 92.3%, 4.8-17.2% relative standard deviation (RSD) . The assay limit of detection was 0.044 microg/g muscle based on analysis of control muscle . Catfish muscle samples containing incurred florfenicol residues were analyzed in quintuplicate with RSD < 5% . Acid hydrolysis has previously been demonstrated to convert florfenicol and its known metabolites to FFA and to release a significant amount of FFA from nonextractable florfenicol residues in tissues containing incurred residues in other species . By using acid hydrolysis, this method should yield a more accurate estimate of the total florfenicol-related residue level in muscle tissue from florfenicol-treated catfish than could be achieved by solvent extraction alone.

Gan To Kagaku Ryoho, 2003 Jun, 30(6), 837 - 9
{Combination therapy with vinorelbine and gemcitabine in unresectable non-small cell lung cancer}; Araki J et al.; Vinorelbine (VNR) and gemcitabine (GEM) were used in combination to treat 10 patients with unresectable non-small cell lung cancer to study the efficacy, safety, possibility of out-patient administration, and improvement of subjective symptoms . One course of treatment consisted of i.v . drip infusion of VNR at 25 mg/m2 followed by i.v . drip infusion of GEM at 1,000 mg/m2 on day 1 and day 8 . This course was repeated more than twice, as a rule, at 3-week intervals . In 10 patients registered from November 1999 to March 2000, we observed PR in 5, SD in 4 and PD in 1 . The response rate was 50% . PS was improved in 5 out of 6 patients with PS 1 or worse . All 4 patients with subjective symptoms reported improvement . Adverse effects of leukopenia of grade 3 or more occurred in 50% of patients and neutropenia in 80% . By dose reduction, we could administer 7.1 courses to each patient on average . Non-hematological toxicities, excluding eruption of grade 3 which occurred in the first course and made it impossible to continue the treatment, were phlebitis in 40% of patients, anorexia in 30% (only grades 1 and 2) and transient drug fever (only grade 1) in 50% . All were tractable, and no lung toxicity occurred . Antibiotic chemotherapy could be performed in 7 patients on an outpatient basis . Combination therapy with VNR and GEM also seemed to be a safe and useful treatment on an outpatient basis.

Gan To Kagaku Ryoho, 2003 Jun, 30(6), 755 - 9
{Bone marrow suppression--including guidelines for the appropriate use of G-CSF}; Watanabe T; For previously untreated patients receiving most chemotherapy regimens, primary prophylactic administration of granulocyte colony-stimulating factor (G-CSF) cannot be recommended . Secondary prophylactic G-CSF administration can lessen incidence of febrile neutropenia (FN) in subsequent cycles of chemotherapy in patients with a prior episode of FN . Physicians should consider chemotherapy dose reduction after neutropenic fever or severe or prolonged neutropenia after the previous cycle of treatment . Intervention with G-CSF in afebrile neutropenic patients is not recommended . For the majority of patients with FN, the available data do not clearly support the routine initiation of G-CSF as an adjunct to antibiotic therapy . However, certain FN patients may have prognostic factors that are predictive of clinical deterioration, such as pneumonia, hypotension, multiorgan dysfunction (sepsis syndrome), or fungal infection . The therapeutic use of G-CSF together with antibiotics may be reasonable in such high-risk patients . Empirical antifungal therapy is effective, especially for patients with neutropenia who were treated for seven days with empirical antibiotic therapy but remained febrile, or became afebrile but then had recurrent fever . The patient's overall clinical status and laboratory parameters are both considered when deciding to transfuse a patient . Epoetin may be available for use in the future as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin level less than 10 g/dl . Giving prophylactic platelets at a threshold of 10,000/microliter compared with 20,000/microliter can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.

J Obstet Gynaecol, 2003 May, 23(3), 258 - 60
Incidence and aetiological factors of incisional hernia in post-caesarean operations in a Nigerian hospital; Adesunkanmi AR et al.; Caesarean operations accounted for most of the postoperative incisional hernias seen in our surgical clinic . In order to determine the incidence and aetiological factors of incisional hernia, all the women who had caesarean operations were reviewed retrospectively . There were 22 cases of incisional hernia, accounting for 3.1% of total 701 patients who had caesarean sections during the period of the study . The incidence of incisional hernia was influenced by the type of incision, as all those who developed incisional hernia had a midline incision, the need for additional operative procedures and antibiotic administration longer than usual with more potent antibiotics . Presence of postoperative abdominal distention, intra-abdominal sepsis, residual intra-abdominal abscess, wound infection and wound dehiscence and postoperative fever also contributed significantly to the incidence of incisional hernia . Those who developed incisional hernias also suffered other postoperative complications and stayed longer in the hospital after the operation . The age of the patients, the parity and indication for caesarean section did not influence the incidence of incisional hernia in this study.

J Gastrointest Surg, 2003 Jul-Aug, 7(5), 606 - 26
Evaluation and management of patients with recurrent peptic ulcer disease after acid-reducing operations: a systematic review; Turnage RH et al.; This systematic review examines the evidence for commonly employed strategies of managing patients with recurrent ulcer disease after acid-reducing operations . Particular attention is given to recent evidence relating Helicobacter pylori (H . pylori ) and nonsteroidal anti-inflammatory drugs (NSAIDs) to ulcer recurrence after operative therapy . MEDLINE word searches of the literature from 1966 to 2001 identified 895 articles that cross-reference the terms "peptic ulcer disease (PUD)," "surgery," and "recurrence." Articles were selected for systematic review of evidence relating incomplete vagotomy, NSAIDs, and H . pylori to postoperative ulcer recurrence and evidence supporting common medical and surgical strategies . The relationship between incomplete vagotomy and recurrent ulcer disease is suggested by randomized controlled trials and well-designed prospective case series . The evidence that NSAID use is an important pathogenic factor in recurrent ulcer disease includes the relationship between NSAIDs and primary PUD, the occurrence of NSAID-induced ulcers in patients taking proton pump inhibitors, and case series demonstrating virulent ulcer disease in patients taking aspirin despite prior acid-reducing operations . The relationship between H . pylori infection and postoperative ulcer recurrence remains uncertain despite multiple controlled trials and well-designed case series that have documented high rates of H . pylori infection in postoperative patients . The initial management of patients with recurrent ulcer disease after acid-reducing operations consists of a protein pump inhibitor or a histamine-2 receptor antagonist and antibiotics directed at H . pylori, if present . Evidence for this regimen includes prospective randomized trials demonstrating the efficacy of cimetidine in healing ulcers after acid-reducing operations and prospective, randomized studies documenting the efficacy of histamine-2 receptor antagonists and protein pump inhibitors in the management of patients with primary PUD . The critical role that H . pylori infection plays in primary PUD and the minimal risks associated with H . pylori eradication strongly support the initiation of antibiotic therapy when H . pylori is present . The principal indication for operative management of recurrent PUD is the occurrence of ulcer complications that cannot be managed by medical or endoscopic means . The operative management of patients with failed acid-reducing operations is based on ulcer recurrence rates and morbidity and mortality rates in randomized and nonrandomized prospective trials of patients with primary PUD and retrospective case series of patients undergoing remedial operative procedures after various failed acid-reducing operations.

J Am Chem Soc, 2003 Jul 16, 125(28), 8561 - 5
Asymmetric synthesis of (2S,3R)-capreomycidine and the total synthesis of capreomycin IB; DeMong DE et al.; A 27 step total synthesis of the tuberculostatic macrocyclic peptide antibiotic capreomycin IB has been accomplished . The synthesis features the use of an enolate-aldimine condensation between a chiral glycine aluminum enolate and the benzyl imine of 3-tert-butyldimethylsiloxy-propanal as a means of preparing the cyclic guanidine amino acid (2S,3R)-capreomycidine . Additionally, a Hofmann rearrangement was exacted on a late-stage pentapeptide in order to transform an asparagine residue into a diaminopropanoic acid residue.

Crit Care Clin, 2003 Jul, 19(3), 473 - 87
Pediatric intensive care unit nosocomial infections: epidemiology, sources and solutions; Rowin ME et al.; Nosocomial infections in the PICU remain a significant source of morbidity and mortality . The risk of infections in these patients remains high because invasive devices allow organisms to bypass normal host defenses . Additionally, this patient group often has coexisting metabolic or organ system dysfunctions . Antibiotic pressure has led to the development of drug-resistant organisms within the PICU, thereby causing infections that are increasingly difficult to control . The best current approach for preventing PICU infections centers on consistent hand washing between patients, early discontinuation of invasive devices, and appropriate isolation strategies . Insight into the causes and locations of PICU-related infections remains a crucial component in the success of preventive strategies.

J Drugs Dermatol, 2003 Jun, 2(3), 320 - 3
Minocycline-induced immune thrombocytopenia presenting as Schamberg's disease; D'Addario SF et al.; Minocycline hydrochloride, a synthetic tetracycline, is a systemic antibiotic that has received much attention over the past several years . Currently, minocycline is considered the most widely prescribed oral antibiotic in the management of acne . Minocycline has been associated with autoimmune events, hepatitis, lupus-like syndromes, serum sickness, vasculitis, Sweet's syndrome, and hyperpigmentation . We report a case of a patient who developed drug-induced immune thrombocytopenic purpura (DITP) after taking minocycline . The initial clinical presentation of nonpalpable, discrete nonblanching petechiae and cayenne pepper-like macules on his lower legs was diagnosed as pigmented purpuric dermatosis (Schamberg's disease) . We report the first case of DITP with the clinical picture of Schamberg's disease associated with minocycline therapy.

J Pediatr Hematol Oncol, 2003 Jul, 25(7), 553 - 7
Efficacy of prophylactic use of trimethoprim-sulfamethoxazole in autoimmune neutropenia in infancy; Kobayashi M et al.; PURPOSE: Most children with autoimmune neutropenia (AIN) have a benign clinical course because of the spontaneous resolution of neutropenia . The authors observed the clinical course of AIN in infancy accompanied by the prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX) during neutropenia . PATIENTS AND METHODS: Eight infants with AIN were followed by serial tests for antineutrophil antibodies and management of infectious complications . RESULTS: The spontaneous disappearance of antineutrophil antibodies that preceded the normalization of the neutrophil count was found in all patients . Until the resolution of neutropenia, TMP-SMX was administered in five patients, resulting in a reduction in the incidence of infection with no adverse effects . CONCLUSIONS: These observations demonstrate the possibility of the safety and usefulness of TMP-SMX treatment in patients with AIN.

Biochemistry, 2003 Jul 15, 42(27), 8313 - 24
Inhibition of c-src transcription by mithramycin: structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target; Remsing LL et al.; The aureolic acid antitumor antibiotic mithramycin (MTM) inhibits both cancer growth and bone resorption by cross-linking GC-rich DNA, thus blocking binding of Sp-family transcription factors to gene regulatory elements . Transcription of c-src, a gene implicated in many human cancers and required for osteoclast-dependent bone resorption, is regulated by the binding of Sp factors to specific elements in its promoter . Therefore, this gene represents an important anticancer target and a potential lead target through which MTM displays its so far uncharacterized action against osteoclastic bone resorption . Here we demonstrate, using DNA binding studies, promoter reporter assays, and RT-PCR, that MTM inhibits Sp binding to the c-src promoter region, thereby decreasing its expression in human cancer cells . Furthermore, selected mithramycin analogues, namely, premithramycin B, mithramycin SK, 7-demethylmithramycin, 4E-ketomithramycin, and 4C-ketodemycarosylmithramycin, generated through combinatorial biosynthesis, were compared with MTM for their ability to block Sp binding to the c-src promoter . Although most of the tested compounds lost their ability to bind to the DNA, alteration of the MTM 3-pentyl side chain led to a compound (mithramycin SK) with the same DNA binding specificity but with lower binding affinity than MTM . While this compound was comparable to MTM in promoter reporter, gene expression, and anticancer assays, given its weaker interaction with the DNA, it may be much less toxic than MTM . The results presented here supplement recent findings and, moreover, allow new conclusions to be made regarding both the structure-activity relationships, particularly with respect to the alkyl side chains, and the mechanism of action of aureolic acid drugs.

Acta Cardiol, 2003 Jun, 58(3), 211 - 4
Cardiac conduction disturbances in Lyme disease; Swinnen J et al.; A young patient is described presenting with third-degree atrioventricular block, who had a flu-like syndrome a few weeks before admission . The diagnosis of Lyme disease was suspected by serologic antibody detection and confirmed by Western immunoblot assay . Pacing was necessary because an unstable escape rhythm persisted . After treatment, atrioventricular conduction recovered . Lyme disease, a tick borne disease, is discussed with emphasis on cardiac involvement: atrioventricular block is a frequent complication of early disseminated disease . If treated with adequate antibiotic therapy, the prognosis is good.

Breast Cancer Res Treat, 2003 Jun, 79(3), 321 - 8
JNK/SAPK mediates doxorubicin-induced differentiation and apoptosis in MCF-7 breast cancer cells; Kim J et al.; Pharmacologic induction of cancer cell differentiation has potential in the treatment of breast cancer . Doxorubicin, a widely used anthracycline antibiotic, was previously reported to induce differentiation of MCF-7 breast cancer cells . We demonstrate in this study that inhibition of MCF-7 breast cancer cell growth by low dose doxorubicin (0.01 microg/ml) was accompanied by an increase in cytokeratin 8/18 and milk fat globule membrane protein expression, biomarkers for differentiation of breast cancer, as well as an increase in JNK/SAPK phosphorylation . High dose doxorubicin (10.0 microg/ml) induced apoptosis in these cells . Overexpression of dominant-inhibitory forms of JNK1 and c-Jun blocked both the differentiation and apoptotic effects of doxorubicin . These results suggest that JNK/SAPK pathway signaling plays a prominent role in doxorubicin-induced cell cycle withdrawal, differentiation and control of apoptosis in this cell system . These findings support the possibility that JNK/SAPK pathway activation may be a means of therapeutic intervention in breast cancer.

Shokuhin Eiseigaku Zasshi, 2003 Apr, 44(2), 114 - 8
{Residue analysis of spectinomycin in tissues of chicken and swine by HPLC}; Hamamoto K et al.; A reversed-phase HPLC method with ultraviolet detection using p-nitrophenyl hydrazine as a pre-column derivatizing reagent was investigated for the determination of the antibiotic spectinomycin (SPCM) in muscle, liver, kidney and fat of chicken and swine . SPCM was extracted from samples with 10% trichloroacetic acid saturated with EDTA-2Na, and then cleaned up with coupled Sep-Pak Plus PS-2 cartridges . The detection limit of SPCM was 0.02 microgram (potency)/g . Recoveries of SPCM ranged from 77.4 to 97.4% for chicken tissues and from 74.5 to 91.8% for swine tissues . The present method was used for the analysis of chicken tissues after the 11th day of withdrawal (SPCM-medicated drinking water: 500 mg (potency)/L, for 7 days), and swine tissues after the 14th day of withdrawal (SPCM-medicated feed: 100 mg (potency)/kg, for 7 days) . Results showed that SPCM concentrations were lower than the MRLs in all tissues.

Rev Prat, 2003 May 15, 53(10), 1102 - 8
{The diabetic foot}; Hartemann-Heurtier A et al.; Diabetic patients are concerned with foot complications when a peripheral neuropathy is present . Screening of predisposed patients may be annually assessed using monofilament testing . Peripheral arterial disease, when associated, increases amputation risk . Ideal treatment requires a multidisciplinary approach with a first-line medical treatment including an optimal off-loading of the diabetic ulcer, ulcer dertersion, glycemic control, and if necessary antibiotic therapy . In case of associated osteomyelitis, a limited surgical resection of the infected bone may be performed . In case of associated arterial disease, a revascularization procedure precede bone resection.

Circ J, 2003 Jul, 67(7), 585 - 91
Survey of prophylaxis and management of infective endocarditis in patients with congenital heart disease: Japanese nationwide survey; Niwa K et al.; Guidelines for the prevention and management of infective endocarditis (IE) in children with congenital heart disease (CHD) have not been established, so the aim of this study was to clarify the incidence, practical prevention and management of IE in patients with CHD in Japan through a nationwide survey . A written questionnaire was sent to members of the Japanese Society of Pediatric Cardiology and Cardiac Surgery and information was obtained from 236 cardiologists in 228 institutions . Four hundred and eight patients with IE were hospitalized during 1997 to 2001 (1/173 admissions with CHD including those hospitalized for cardiac catheterization or surgery) . Prevention of IE for CHD was undertaken by 92% of cardiologists, usually oral penicillins (73%) and less frequently cephems (18%) were prescribed . The Duke criteria were used as clinical criteria by 38% . Blood culture was performed once only by 40% . Penicillins and aminoglycosides (38%) were frequently administered for management of culture-negative IE . There were variations in the dose and duration of antibiotics for prevention and management of IE . It appears that the prevalence of IE in CHD is rising and the nationwide survey revealed more variations in practical prevention and management of IE in patients with CHD than expected . The results should be helpful in making future guidelines for management of IE in CHD.

Ann Dermatol Venereol, 2003 May, 130(5), 515 - 8
{Mycetomas in central Tunisia}; Denguezli M et al.; INTRODUCTION: Mycetomas are inflammatory pseudo-tumors containing fungal or actinomycosic-type grains . They are frequent in tropical and subtropical countries and unknown in Tunisia . PATIENTS AND METHODS: We conducted a retrospective study of 12 cases of mycetoma registered in the Dermatological department of the university hospital in Sousse (central Tunisia) over a period of 27 years, from 1974 to 2001 . The diagnosis was confirmed by anatomopathological and/or mycological examination . RESULTS: The mean age at the onset was of 49 years and the sex ratio of 1 . A notion of a traumatism was reported in two cases and eight patients had various agricultural activities . The mean duration of progression was of eight years . The localization was the foot in 10 cases . The mycetoma was of actinomycosic origin in 10 cases, due to Actinomadura madurae in nine cases, to Nocardia spp in one case and of fungal origin in 2 cases:Pseudoallescheria boydii in one case and Madurella mycetomi in the other . Antibiotic therapy was associated with surgical exeresis in nine cases and amputation in the other two cases . COMMENTS: Confrontation of our results with those of Tunisian series and a review of the literature, helped to specify the clinico-epidemiological characteristics and progression of mycetoma in Tunisia . These characteristics are: the rareness of the infection, the relative frequency of affection in women, the proximal involvement of the foot, the frequency of agricultural activity and the rareness of traumatic past history, the predominance of the actinomycosic origin due to Actinomadura madurae, and the need to associate surgical exeresis with the medical treatment or amputation in order to stop the progress of the disease.

J Acquir Immune Defic Syndr, 2003 Jul 1, 33(3), 281 - 91
HIV infection--a risk factor for osteoporosis; Thomas J et al.; Osteopenia and osteoporosis have recently been described as complications of antiretroviral therapy in HIV-infected patients . The advent of highly active antiretroviral therapy in conjunction with improved standard antiviral and antibiotic regimens has dramatically changed the clinical course of HIV infection, resulting in prolonged survival . The pathogenesis and role of each individual medication are poorly understood . Avascular necrosis has also been described in AIDS patients receiving or not receiving antiretroviral therapy . This article is a clinically focused review of the literature on osteopenia, osteoporosis, and mineral metabolism related to HIV infection . In patients with HIV infection, the risks of osteopenia and osteoporosis are not very clear . The suggested risk factors for the development of osteopenia are use of protease inhibitors, longer duration of HIV infection, high viral load, high lactate levels, low bicarbonate levels, raised alkaline phosphatase level, and lower body weight before antiretroviral therapy . There have also been a few case reports of pathologic fractures in AIDS patients with antiretroviral therapy-induced osteopenia and osteoporosis . The underlying mechanism triggering bone loss in HIV-infected patients is unknown . The proinflammatory cytokines tumor necrosis factor and interleukin-6 have been found to be constitutionally produced in increased amounts in HIV-positive individuals, and they may have a role in osteoclast activation and resorption . Serum markers of bone formation are decreased and resorption is increased in patients with advanced clinical disease . Hypocalcemia, hypercalcemia, and abnormalities of the parathyroid hormone axis have been described in HIV infection . Histomorphometric analyses have shown altered bone remodeling in HIV-infected patients when compared with controls . Patients with known risk factors for osteoporosis-advancing age, low body weight, and prolonged duration of HIV infection-and those receiving protease inhibitor treatment should be considered for dual x-ray absorptiometry imaging . If bone mineral density is osteopenic or osteoporotic, then the patient should also be screened for other known medical causes of osteoporosis and consider treatment with a bisphosphonate or, if hypogonadal, testosterone replacement under close monitoring.

J Cataract Refract Surg, 2003 Jun, 29(6), 1132 - 6
Patient comfort during clear corneal phacoemulsification with sub-Tenon's local anesthesia; Mathew MR et al.; PURPOSE: To assess patient comfort with and without intravenous (i.v.) cannulation during 1-quadrant sub-Tenon's anesthesia during phacoemulsification . SETTING: Royal Alexandra Hospital, Paisley, Scotland, United Kingdom . METHODS: This prospective masked controlled clinical trial comprised 119 patients having elective clear corneal phacoemulsification . Fifty had sub-Tenon's anesthesia with an i.v . cannula; 23, sub-Tenon's anesthesia without an i.v . cannula; and 46, topical anesthesia of proparacaine 0.5% without an i.v . cannula . No patient received sedation . All patients had clear corneal phacoemulsification with foldable posterior chamber intraocular lens implantation . The patients' subjective pain experience was measured immediately after surgery by a single independent observer using a 10-point visual analog scale . RESULTS: The mean patient-reported pain was low in all 3 groups . The mean i.v . cannula-related pain score in the sub-Tenon's group with an i.v . cannula (1.00; range 0 to 8) was higher than the mean general pain score (0.46; range 0 to 5) and worst pain experienced during surgery score (0.64; range 0 to 3) . In the topical anesthesia group, 8 patients (17%) reported greater discomfort directly or indirectly related to the subconjunctival antibiotic injection at the end of surgery . CONCLUSION: Patient-reported pain caused by placing an i.v . cannula in the sub-Tenon's group significantly altered overall patient comfort during the surgical experience . Thus, the routine use of i.v . access during clear corneal phacoemulsification under sub-Tenon's anesthesia should be avoided to improve patient satisfactionPublication Types:

	Clinical Trial
	Randomized Controlled Trial

What Is Genetics?, What Is Anthrax?, What Is Listeria Monocytogenes?, What Is Protein?, What Is MIC?, i, Microbiology, a, Microbe, e, Bacteria, c, Microbes, a, Bacterium, r, Bacteria, c, Pseudomonas aeruginosa, o, Bacillus, o, Suspension cells, i, Escherichia coli, a, Bactericidal, a, Bacillus, s, Antibiotics, i, Bacteria, i, Streptococci, c, Yeasts, c, Microorganisms, r, Escherichia coli, i, Cell suspensions, r, Gram positive, r, Pseudomonas aeruginosa, c, Antibiotics, a, Bacillus subtilis, i, Antibiotics, s, Escherichia coli, o, Cell cultures

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005