Minerva Cardioangiol, 1997 Oct, 45(10), 467 - 70 Timing for surgical treatment in native infective endocarditis . A seven-year experience; Triggiani M et al.; BACKGROUND: Early surgical intervention in infective endocarditis is performed only when there is persistence of sepsis, hemodynamic instability or when arterial embolism has occurred, otherwise a 4-week antibiotic therapy before surgery is considered necessary . Our 7-year experience in the surgical treatment of native endocarditis in 28 patients, is here revised focusing on the timing of surgery . METHODS: Patients were retrospectively divided into group A (n . 16) with blood cultures that became negative before surgery and group B (n . 11) with blood cultures positive at the time of urgent surgery . One patient with constantly negative blood cultures was not assigned to any group . In group A antibiotic therapy was administered until 3 consecutive blood cultures became negative and the patients were then operated on the basis of echocardiographic findings after a mean duration of antibiotic therapy of 17.4 +/- 6.3 days . RESULTS: Twenty-six patients out of 28 underwent replacement of the infected valve (mechanical bileaflets in 16 patients, porcine stented in 7 and porcine stentless in 3) . Valve repair was performed in 2 patients . Overall operative mortality was) 7.1% (2/28); death occurred in 2 patients of group B, operated on for cardiogenic shock . Two/26 patients died (1 acute renal failure and 1 stroke) at a mean follow-up of 32.5 +/- 24.8 (range 3-95) months . CONCLUSIONS: Patients who underwent surgery for infective endocarditis after blood culture negativization showed no mortality and no recurrence of disease even if a 4 weeks antibiotic course was not completed . This experience suggests that earlier operations can be performed safely, lowering the incidence of hemodynamic impairment and arterial embolism. Acta Stomatol Belg, 1996 Sep, 93(3), 125 - 8 Mediastinitis as a rare complication of an odontogenic infection . Report of a case; Morey-Mas M et al.; Mediastinitis occasionally develops as a complication of cervical or odontogenic infections resulting in neck sepsis, which spreads to the mediastinum via the cervical facial planes . Nowadays, this rare complication of pyogenic orofacial infections has an high-unchanged mortality rate . Delayed diagnosis and inadequate mediastinal drainage are the primary causes of this high mortality rate . Aggressive empirical antibiotic combinations should be directed towards this polymicrobial process . Antibiotic therapy alone is inadequate and the mainstay of treatment is aggressive surgical drainage through cervical and thoracic approaches . The assessment and management of the airway is critical; most authors recommend early tracheostomy in a controlled fashion in all cases of serious neck infections with or without thoracic involvement . However, we consider tracheostomy not always necessary and we only perform it in patients with severe dyspnea from upper airway obstruction. J Fam Pract, 1998 Feb, 46(2), 147 - 52 Factors influencing the clinical diagnosis of sinusitis; Little DR et al.; BACKGROUND: This study was conducted to determine the influence of various clinical factors on the physician's diagnosis of sinusitis . Although the "clinical impression" appears to be a valid method of diagnosis in the literature, the specific factors that influence it have not been explored . METHODS: Seven factors selected from the literature were incorporated into 128 simulated case histories of patients with possible sinusitis . These cases were presented to 40 local family physicians who were asked to assess whether sinusitis was present and whether antibiotic therapy would be prescribed . Logistic regression was performed to determine the influence of each factor . These results were compared with a 30-item Likert-type scale that asked the physicians to rate a variety of factors in terms of their importance to the diagnosis of sinusitis . RESULTS: The diagnosis of sinusitis and the decision to prescribe antibiotics were strongly influenced by the number of factors present . Physicians placed the most emphasis on purulent drainage seen on examination and sinus tenderness, and the least emphasis on smoking history and the failure to respond to decongestants . Transillumination and x-ray examinations were less useful to these physicians in establishing the diagnosis . CONCLUSIONS: The surveyed physicians based their diagnosis of sinusitis on the number of symptoms present, especially if the presentation included purulent drainage seen on examination or sinus tenderness . These results are consistent with studies that have approached the question using other designs. Int J Gynaecol Obstet, 1997 Dec, 59(3), 233 - 6 Intraoperative blood salvage in abdominal simple total hysterectomy for uterine myoma; Yamada T et al.; OBJECTIVE: To investigate the safety and usefulness of salvage-type autologous blood transfusion for abdominal simple total hysterectomy for uterine myoma . METHODS: Forty patients with uterine myoma diagnosed histologically were treated by abdominal simple total hysterectomy using an intraoperative blood salvage apparatus . Bacterial contamination in the processed blood was studied . RESULTS: Homologous blood transfusion was unnecessary . There was a positive relationship between bleeding volume and the hemoglobin (g) level in the processed blood . All vaginal swabs were positive for bacteria . Bacterial cultures of all processed blood samples without an antibiotic were positive whereas results were negative in 11 (50%) of the processed blood samples with an antibiotic . There were no significant side effects after reinfusion . CONCLUSION: Salvage-type autologous blood transfusion in abdominal simple total hysterectomy for uterine myoma was safe and its future use is promising. Stat Med, 1998 Jan 30, 17(2), 201 - 18 Approximate Bayesian inference for random effects meta-analysis; Abrams K et al.; Whilst meta-analysis is becoming a more commonplace statistical technique, Bayesian inference in meta-analysis requires complex computational techniques to be routinely applied . We consider simple approximations for the first and second moments of the parameters of a Bayesian random effects model for meta-analysis . These computationally inexpensive methods are based on simple analytical formulae that provide an efficient tool for a qualitative analysis and a quick numerical estimation of posterior quantities . They are shown to lead to sensible approximations in two examples of meta-analyses and to be in broad agreement with the more computationally intensive Gibbs sampling. Ann Thorac Surg, 1998 Feb, 65(2), 319 - 23 Video-assisted thoracoscopic surgery for fibrinopurulent pleural empyema in 67 patients; Striffeler H et al.; BACKGROUND: The roles of different drainage procedures in the management of empyema have to be redefined now that video-assisted thoracoscopic surgery (VATS) has been introduced . The debridement of fibrinopurulent stage II empyema with the use of VATS was assessed prospectively in regard to control of infection and restoration of pulmonary function . METHODS: Between January 1992 and May 1996, all patients at our institution with fibrinopurulent empyema that did not respond to chest tube drainage and antibiotic therapy were treated by debridement with the use of VATS . The patients were followed up prospectively by clinical and radiologic assessments 3 and 6 months after the operation and by spirometry 6 months after the operation . RESULTS: Video-assisted thoracoscopic surgery was initiated in 67 patients, but conversion to open decortication was required because of the finding of advanced disease in 19 patients (28%) . Forty-eight patients underwent successful debridement with the use of VATS . The mean operative time was 82.1 minutes (range, 50 to 135 minutes), the mean duration of postoperative chest tube placement was 4.1 days (range, 2 to 8 days), and the mean duration of postoperative hospitalization was 12.3 days (range, 4 to 42 days) . No wound infections were observed during the postoperative course . Both the 30-day mortality rate and the recurrence (ie, need for thoracotomy) rate were 4% . The mean predicted vital capacity was 84.8% +/- 14.9% and the mean predicted forced expiratory volume in 1 second was 88.6% +/- 19.2% 6 months after the operation . CONCLUSIONS: Debridement with the use of VATS is safe and efficient for stage II empyema, but open decortication should be used for more advanced disease. J Antimicrob Chemother, 1997 Dec, 40 Suppl A, 35 - 43 Pharmacokinetics of grepafloxacin; Efthymiopoulos C; Grepafloxacin is a fluoroquinolone antibiotic which is rapidly absorbed in healthy volunteers following oral dosing . It reaches peak plasma levels around 2 h after administration, then declines bi-exponentially, with an extended half-life of around 12 h . Grepafloxacin is eliminated primarily through metabolism and is excreted mainly in the faeces . Renal clearance accounts for only 10-15% of the administered dose . Grepafloxacin plasma concentrations increase disproportionately with increasing doses, but this is unlikely to be of clinical significance over the range of therapeutic doses . The rate and extent of absorption are not affected by food or elevated intragastric pH . The pharmacokinetics of grepafloxacin are affected by gender, with these differences relating to variations in body weight . No effect of age on the pharmacokinetics of grepafloxacin was found . Renal impairment does not affect grepafloxacin pharmacokinetics, whereas peak plasma concentrations, areas under plasma concentration-time curves and renal excretion are increased in patients with hepatic impairment . Grepafloxacin can be co-administered with warfarin and theophylline, though reduction of the theophylline dose is necessary . Following oral administration, higher grepafloxacin concentrations are achieved in lung and genital tissues than in serum, indicating its potential in the treatment of respiratory and sexually transmitted diseases . In addition, it exceeds therapeutically effective levels in bile and gall-bladder tissues, and accumulates in polymorphonuclear leucocytes such that it may be useful against intracellular pathogens. Virus Genes, 1997, 15(3), 235 - 45 The DNA sequence of Chilo iridescent virus between the genome coordinates 0.101 and 0.391; similarities in coding strategy between insect and vertebrate iridoviruses; Bahr U et al.; Chilo iridescent virus (CIV), the type species of the genus Iridovirus within the family Iridoviridae, is highly pathogenic for larvae of important pest insects . The virions contain a single linear double-stranded DNA molecule (209 kbp) that is circularly permuted and terminally redundant . The nucleotide sequence of the viral genome between the genome coordinates 0.101 and 0.391 (60,170 bp) was determined by automated cycle sequencing . This particular region of the CIV genome contains 112 open reading frames (ORFs) with coding capacities for 50 to 1186 amino acids . The alignment of the deduced amino acid sequences with well-characterized proteins stored in protein databases led to the identification of several genes with significant homologies, such as the largest subunit of the DNA-dependent RNA polymerase, large subunit of the ribonucleoside-diphosphate reductase, endonuclease, protein-tyrosine phosphatase, helicase, global transactivator, two apoptosis inhibitor homologs, antibiotic peptide homolog, and others . The highest homologies were detected between putative viral gene products of CIV and the corresponding viral proteins of lymphocystis disease virus of fish (LCDV), which belongs to the genus Lymphocystivirus within the iridovirus family. Lancet, 1998 Feb 7, 351(9100), 404 - 8 Randomised controlled trial of clinical outcome after chest radiograph in ambulatory acute lower-respiratory infection in children; Swingler GH et al.; BACKGROUND: When available, chest radiographs are used widely in acute lower-respiratory-tract infections in children . Their impact on clinical outcome is unknown . METHODS: 522 children aged 2 to 59 months who met the WHO case definition for pneumonia were randomly allocated to have a chest radiograph or not . The main outcome was time to recovery, measured in a subset of 295 patients contactable by telephone . Subsidiary outcomes included diagnosis, management, and subsequent use of health facilities . FINDINGS: There was a marginal improvement in time to recovery which was not clinically significant . The median time to recovery was 7 days in both groups (95% CI 6-8 days and 6-9 days in the radiograph and control groups respectively, p=0.50, log-rank test) and the hazard ratio for recovery was 1.08 (95% CI 0.85-1.34) . This lack of effect was not modified by clinicians' experience and no subgroups were identified in which the chest radiograph had an effect . Pneumonia and upper-respiratory infections were diagnosed more often and bronchiolitis less often in the radiograph group . Antibiotic use was higher in the radiograph group (60.8% vs 52.2%, p=0.05) . There was no difference in subsequent use of health facilities . INTERPRETATION: Chest radiograph did not affect clinical outcome in outpatient children with acute lower-respiratory infection . This lack of effect is independent of clinicians' experience . There are no clinically identifiable subgroups of children within the WHO case definition of pneumonia who are likely to benefit from a chest radiograph . We conclude that routine use of chest radiography is not beneficial in ambulatory children aged over 2 months with acute lower-respiratory-tract infectionPIP: The impact of chest radiographs on the diagnosis, treatment, follow-up, and clinical outcome of children with ambulatory acute lower-respiratory infections was assessed in 518 children 2-59 months old who presented to the Red Cross Hospital in Cape Town, South Africa, with symptoms consistent with the World Health Organization case definition of pneumonia . 257 were randomly assigned to receive a radiograph and 261 were controls (no diagnostic intervention) . The median time to recovery, measured in a subset of 295 children whose parents were reachable by telephone, was 7 days for both cases and controls (95% confidence intervals, 6-8 and 6-9 days, respectively) . The unadjusted Cox proportional hazards ratio for recovery for the radiograph group compared with controls was 1.08 (95% confidence interval, 0.85-1.34) . This rate was unaffected by adjustment for age, weight for age, duration of symptoms before presentation, respiratory rate, clinician's postgraduate pediatric qualifications, and clinician's perception of the need for chest radiograph . More radiograph patients were diagnosed with pneumonia or upper-respiratory infection, while a higher proportion of controls were diagnosed as having bronchiolitis . 149 children in the radiograph group (60.8%) compared with 133 controls (52.2%) received antibiotics . There was no difference in subsequent use of health facilities . These findings indicate that there are no clinically identifiable subgroups of children likely to benefit from routine use of chest radiography . J Craniofac Surg, 1997 Jul, 8(4), 323 - 5 A delayed complication with steel wire osteosynthesis; Rovati LC et al.; We treated a 6-year-old child for hyperteleorbitism . We performed a facial bipartition steel wire osteosynthesis of the frontal bone . After 7 years we observed two episodes of pneumococcal meningitis, which were treated with intravenous antibiotic, resulting in a prompt recovery . The computed tomographic scan and nuclear magnetic resonance image showed the steel wire included in the frontal sinus and in contact with the dura mater . Removal of the wire and suture of the dura allowed prompt recovery. Clin Nucl Med, 1998 Feb, 23(2), 74 - 6 Infected cardiac pacemaker wires demonstrated by Tc-99m labeled white blood cell scintigraphy; Howarth DM et al.; Multiple cardiac pacing wires present a potential source of thrombosis and infection within veins and cardiac chambers . A case is presented where persistent infection involved thrombus on cardiac pacing wires in and around the right subclavian and brachiocephalic veins, which proved difficult to localize and treat . Early Ga-67 and Tc-99m labeled white blood cell imaging were negative but, when the latter test was repeated after 5 weeks, the septic focus was identified . Treatment with antibiotic therapy combined with surgical removal of the infected thrombus and both pacing wires was effective in eradicating infection . Failure to demonstrate an infection focus early in the course of the illness may have related to the size of the infection focus; however, in a later phase of the illness, Tc-99m labeled white blood cell imaging proved helpful in localizing focal infection associated with pacemaker wires. Nucleic Acids Res, 1997 Dec 15, 25(24), 5077 - 84 Minor groove DNA alkylation directed by major groove triplex forming oligodeoxyribonucleotides; Lukhtanov EA et al.; We describe sequence-specific alkylation in the minor groove of double-stranded DNA by a hybridization-triggered reactive group conjugated to a triplex forming oligodeoxyribonucleotide (TFO) that binds in the major groove . The 24 nt TFOs (G/A motif) were designed to form triplexes with a homopurine tract within a 65 bp target duplex . They were conjugated to an N 5-methyl-cyclopropapyrroloindole (MCPI) residue, a structural analog of cyclopropapyrroloindole (CPI), the reactive subunit of the potent antibiotic CC-1065 . These moieties react in the DNA minor groove, alkylating adenines at their N3 position . In order to optimize alkylation efficiency, linkers between the TFO and the MCPI were varied both in length and composition . Quantitative alkylation of target DNA was achieved when the dihydropyrroloindole (DPI) subunit of CC-1065 was incorporated between an octa(propylene phosphate) linker and MCPI . The required long linker traversed one strand of the target duplex from the major groove-bound TFO to deliver the reactive group to the minor groove . Alkylation was directed by relative positioning of the TFOs . Sites in the minor groove within 4-8 nt from the end of the TFO bearing the reactive group were selectively alkylated. J Trop Pediatr, 1997 Dec, 43(6), 361 - 3 Cerebro-spinal lactate status in childhood pyogenic meningitis in Nigeria; Imuekehme S et al.; This study was undertaken to ascertain the status of cerebrospinal (CSF) lactate level in Nigerian children with pyogenic meningitis . Forty patients aged from 1 month to 12 years with proven meningitis were the subjects in the study which lasted 8 months . All the patients who had pyogenic meningitis had mean cerebrospinal lactate level over 25 mg/dl . The patients who recovered with neurological deficit had higher level of cerebrospinal lactate than those who recovered without any neurological deficit, on admission and on-discharge, although the differences were not statistically significant . The patients who died had persistently high mean CSF lactate on admission and at death . The study suggests that persistently elevated CSF lactate in cases of pyogenic meningitis receiving adequate antibiotic therapy might indicate poor prognosis with increased mortality . It is not being suggested that CSF lactate determination should replace the conventional tests for meningitis . However, it can provide pertinent, rapid, and reliable diagnostic information, and can also provide useful evaluation information at different stages of treatment of proven meningitis with appropriate antibiotics. Leuk Lymphoma, 1997 Nov, 27(5-6), 469 - 74 High dose cytosine arabinoside is a major risk factor for the development of hepatosplenic candidiasis in patients with leukemia; Woolley I et al.; A retrospective study of hepatosplenic candidiasis in patients with acute leukemia from a single centre was performed . The significance of age, sex, type of leukemia, dose of cytosine arabinoside (Ara-C), duration of neutropenia, steroid use and period of therapeutic antibiotics in the development of hepatosplenic candidiasis was analyzed, using logistic regression analysis . Nine of 51 patients had hepatosplenic candidiasis . Ara-C use was highly associated with the development of hepatosplenic candidiasis (p = 0.001); with a high association with a higher dose (p < 0.0001) . On the basis of these results consideration should be given to further trial of antifungal prophylaxis for patients receiving high dose Ara-C. HNO, 1997 Nov, 45(11), 891 - 7 {Bite injuries in the head and neck area}; Scheithauer MO et al.; In Germany about 8500 dog-bite injuries in the face occur every year; more than 50% of the victims are infants and schoolchildren . Besides dogs, other animals such as cats or horses may be responsible for these accidents . Even human bites are reported . The predominant areas are the nose and the auricles . The tissue defects may be superficial, but they can even cause amputations, including severe vascular and nerve or bony destruction . Systemic antibiotic therapy is needed when the wound is infected . The surgical approach to bite injuries includes local wound cleansing, careful excision of necrotic tissue and primary closure of the wound whenever possible . Regarding the importance of surgery in the head and neck area plastic-reconstructive techniques including autologous transplantations and various local or regional flaps should be used at the time the wound is first repaired. Fam Pract, 1997 Dec, 14(6), 455 - 60 GP's management of genital Chlamydia: a survey of reported practice; Stokes T et al.; BACKGROUND: Genital chlamydial infection is the commonest curable sexually transmitted disease in the industrialized world . Little is known about how GPs manage this condition . OBJECTIVES: We aimed to determine current knowledge concerning genital chlamydia among GPs and to establish how patients with this infection are managed in primary care . METHODS: A confidential self-administered postal questionnaire survey was sent to all 494 GPs in one English health district (Leicestershire) . RESULTS: Completed questionnaires were returned by 290 GPs (a response rate of 59%) . A much higher proportion of GPs had tested and/or treated female patients for chlamydia {70%, 95% confidence interval (CI) 64-75%} as opposed to male patients (20%, CI 15-25%) . Female patients (70%, CI 64-75%) were also more likely to be managed in general practice than male patients (56%, CI 50-62%) . A majority of GPs (66%, CI 60-72%) routinely used an appropriate method of testing for chlamydia although a high vaginal swab, an inappropriate method of testing, was used by a fifth of GPs (19%, CI 15-24%) . A large number of different treatment regimes were used by GPs . The majority of GPs (85%, CI 79-89%) prescribed an appropriate antibiotic although few GPs (19%, CI 14-25%) specified a chlamydia treatment regime in accordance with accepted international guidelines with respect to drug, dosage and duration of therapy . CONCLUSIONS: Female patients with known or suspected genital chlamydial infection are commonly managed in UK general practice . There is scope to improve the management of this infection in general practice. J Chromatogr A, 1998 Jan 16, 793(2), 283 - 96 High-performance liquid chromatographic separation of enantiomers of unusual amino acids on a teicoplanin chiral stationary phase; Peter A et al.; A glycopeptide antibiotic, teicoplanin, was used as chiral stationary phase for the high-performance liquid chromatographic (HPLC) separation of enantiomers of more than 30 unnatural amino acids, such as phenylalanine and tyrosine analogues and analogues containing 1,2,3,4-tetrahydroisoquinoline, tetraline, 1,2,3,4-tetrahydro-2-carboline, cyclopentane, cyclohexane, cyclohexene, bicyclo{2.2.1}heptane or heptene skeletons . Excellent resolutions were achieved for most of the investigated compounds by using a hydro-organic mobile-phase system . The effects of organic modifier content, temperature and flow-rate on the resolution were investigated and the conditions of separation were optimized. Acta Med Croatica, 1997, 51(4-5), 229 - 32 Adult respiratory distress syndrome; Sutlic Z et al.; In this article the authors present a case of successful treatment of a 54-year old male patient with non-insulin dependent diabetes mellitus (NIDDM) and triple-vessel coronary artery disease who underwent surgical myocardial revascularization and was reoperated on the same day because of excessive bleeding . The patient was given cca 5000 mL of whole blood and cca 3000 mL of blood derivatives . The first postoperative chest X-ray showed radiological signs of ARDS . The therapy was based upon authors' experience and was consisted of controlled mechanical ventilation (respiratory volume 12-15 mL/kg, 10-14 cycles/min, I/E ratio 1:2, FIO2 0.6, PEEP 2-5 cm H2O), daily bronchoscopies with bronchoaspiration, aggressive diuresis, negative fluid balance, specific antibiotic therapy, and last but not least, of prostaglandin E1 (PGE1) 0.5-20 micrograms/kg/min combined with dopamine inotropic support (2-5 micrograms/kg/h) . Simple but careful clinical observation still remains a milestone for all therapeutic measures taken in ARDS patients. Cathet Cardiovasc Diagn, 1998 Jan, 43(1), 63 - 7 Pseudoaneurysm of the thoracic aorta presenting as purulent pericarditis and pericardial effusion; Aranda J Jr et al.; Report of a case of a mycotic pseudoaneurysm of the ascending thoracic aorta occurring in the absence of surgical or blunt trauma in a patient who presented with purulent pericarditis . Surgical pericardial drainage was required, which revealed Staphlococcal aureus . Subsequent transesophageal echocardiogram demonstrated a 4 cm x 4 cm pseudoaneurysm of the posterior wall of the aorta above the sinotubular junction . The patient refused surgical correction of the aortic pseudoaneurysm and was successfully managed with antibiotic therapy. Lijec Vjesn, 1997 Jul, 119(7), 193 - 200 {Patient compliance in the treatment of respiratory tract infections}; Pavic-Sladoljev D et al.; The survey on outpatients compliance in the treatment of respiratory tract infections was performed in Croatia during April 1996 . A total of 213 physicians, 201 adult patients, and 178 parents of sick children were polled by the appropriate questionnaires . The results have shown that in the treatment of respiratory tract infections physicians commonly prescribe thrice-daily antibiotic regimens for 8-10 days . Concerning patients' knowledge, 85% of patients deem that regularity, and 64% that duration of antibiotic administration influences treatment outcome . Over 80% of patients are compliant with once-or twice-daily regimens, but only 50% take regularly and timely drugs that are dosed every 6 or 8 hours . Common reasons for irregular taking of antibiotics are forgetfulness and dosing during sleeping . In terms of appropriate duration of antibiotic therapy, about 20% of patients usually take antibiotic for 8-10 days, 60% for 5-7 days, and 20% for < or = 4 days . It may be concluded that the patients are poorly compliant with oral antibiotics treatment. Lik Sprava, 1997 Jul-Aug, (4), 152 - 4 {Errors in the diagnosis of tumors of the adnexa uteri and the means for their elimination}; Dumanskii IuV et al.; Errors are described made in the course of diagnosis of "false" tumors of the uterine appendages of inflammatory genesis . An algorithm is developed of carrying out differential diagnosis between carcinoma of the ovary and "false" tumours of uterine appendages, involving ultrasonic investigation, computerized tomography and direct endolymphatic antibiotic therapy over a long period of time, which measures permitted a more accurate diagnosis to be made, an adequate surgical treatment to be instituted. G Chir, 1997 Aug-Sep, 18(8-9), 417 - 20 Inflammatory pseudotumor of the liver: case report and review of the literature; Mangiante GL et al.; Inflammatory pseudotumors of the liver (IPL) are extremely rare focal lesions of the parenchyma . Up to now, the ethology of IPL has not been completely understood . Usually the clinical presentation is with fever, chills, hepatic mass . The fine needle biopsy shows a large amount of inflammatory cells, while the most common imaging techniques are not specific and do not reach a definitive preoperative diagnosis between a benign and a malignant tumor . From the examination of the Literature, the Authors found a mortality rate of 40% among patients treated by antibiotic therapy, while surgical procedures were successful in all but one case . Moreover, in Authors' case, successfully treated by hepatic resection, the preoperative diagnostic procedures were not helpful in differential diagnosis with a malignant lesion . For these reasons, the Authors believe surgery is the best therapeutic choice in case of a suspected IPL without an early clinical resolution after antibiotic therapy. Aust Fam Physician, 1997 Dec, 26(12), 1375 - 7 Dog attacks; Young S; BACKGROUND: An estimated 100,000 Australians each year will seek medical attention after a dog attack . Such attacks have the potential to cause significant morbidity especially with regard to soft tissue injury and infection . Proper wound assessment and early intervention will reduce this morbidity . OBJECTIVE: To review the epidemiology, assessment and treatment of soft tissue wounds caused by dog bites . DISCUSSION: Any patient who has been attacked by a dog requires a primary survey for any immediate life threatening problems, a careful assessment of tissue wounds and a treatment regimen that will promote tissue healing and reduce the likelihood of infection . Wounds must be carefully examined for skin loss, joint penetration, and tendon, nerve and vascular injuries, and appropriate action taken if any of these points are detected . The chance of a wound infection will be reduced by thorough cleansing of wounds, debridement and/or delayed primary closure of selected wounds and the judicious use of antibiotics. Chirality, 1998, 10(1-2), 14 - 23 Induction of asymmetry into homodimers; Bardsley B et al.; The self-regulation of biological signalling receptors via homodimerization is discussed in relation to the symmetry changes occurring when these receptors bind their target ligand . The idea of positive and negative cooperativity between dimerization and ligand binding, mediated by changes in the symmetry of the system as a source of signalling control is considered; an analogy made with the homodimerization of a glycopeptide antibiotic, ristocetin A, which displays negative cooperativity . Finally, the regulation of the bacterial aspartate receptor and the human growth hormone receptor is discussed as a function of ligand-induced asymmetry. Eur J Med Res, 1996 Mar 19, 1(6), 299 - 302 Oligosymptomatic neurosyphilis with false negative CSF-VDRL in HIV-infected individuals? Malessa R, Agelink MW, Hengge U, Mertins L, Gastpar M, Brockmeyer NH. The true prevalence of neurosyphilis in HIV-infection is unknown, since a sufficiently sensitive and specific test is lacking . In a prospective study we found reactive serum TPHA and FTA-ABS IgG tests in 95 (31%) of 307 HIV-infected patients . Three of 11 patients with latent syphilis revealed reactive CSF-VDRL tests, six others only demonstrated CSF abnormalities . Resolution of CSF abnormalities during a six month follow up after high dose antibiotic therapy led to the diagnosis of oligosymptomatic or asymptomatic neurosyphilis in all nine patients . Thus, the specificity of the CSF-VDRL was 100%, but the sensitivity was only 33% . The overall prevalence of neurosyphilis was 2.9%, increasing to 9.5% in patients with a reactive serum TPHA . Our study emphasizes the importance of antibiotic therapy for presumptive neurosyphilis in HIV-infected patients with latent syphilis and CSF abnormalities but nonreactive CSF-VDRL tests, even if they are neurologically asymptomatic or present with complaints inconclusive of neurosyphilis. Biol Cell, 1997 Aug, 89(5-6), 293 - 7 A novel method to determine the diffusional water permeability of oocyte plasma membranes; Iserovich P et al.; Measurements of the cell membrane diffusional water permeability (Pd) are important to characterize water passage across water channels and across the lipid bilayer component of the membrane . Existing methods for those measurements are involved; however, we report here a simple procedure to estimate Pd in Xenopus laevis oocytes and similar large cells . Due to the different densities of H2O and D2O (heavy water), an oocyte transferred from normal medium to a D2O-based medium floats initially, but subsequently sinks when a certain amount of the water originally in them is replaced by the D2O that diffuses in . We describe how the 'flotation time' (time that oocytes float in a heavy water solution before they start sinking) yields the Pd of the plasma membrane . Determination of Pd by this procedure and by the rate of tritiated water (T2O) efflux give for Pd results which are very close: 2.2 +/- 0.2 (n = 8) and 2.0 +/- 0.1 (n = 6) microns/s, respectively (T = 10 degrees C) . Furthermore, our method detects the increase in Pd elicited in oocytes by either expression of water channel proteins, or by treating them with the pore-forming antibiotic amphotericin B . This method appears useful to gauge the expression and function of pore-forming, water-permeable membrane proteins. JAMA, 1998 Feb 11, 279(6), 450 - 4 Improved survival among HIV-infected individuals following initiation of antiretroviral therapy; Hogg RS et al.; CONTEXT: Clinical trials have established the efficacy of antiretroviral therapy with double- and triple-drug regimens for individuals infected with the human immunodeficiency virus (HIV), but the effectiveness of these regimens in the population of patients not enrolled in clinical trials is unknown . OBJECTIVE: To characterize survival following the initiation of antiretroviral therapy among HIV-infected individuals in the province of British Columbia . DESIGN: Prospective, population-based cohort study of patients with antiretroviral therapy available free of charge (median follow-up, 21 months) . SETTING: Province of British Columbia, Canada . PATIENTS: All HIV-positive men and women 18 years of age or older in the province who were first prescribed any antiretroviral therapy between October 1992 and June 1996 and whose CD4+ cell counts were less than 0.350 x 10(9)/L . MAIN OUTCOME MEASURES: Rates of progression from initiation of antiretroviral therapy to death or a primary acquired immunodeficiency syndrome (AIDS) diagnosis for subjects who initially received zidovudine-, didanosine-, or zalcitabine-based therapy (ERA-I) and for those who initially received therapy regimens including lamivudine or stavudine (ERA-II) . RESULTS: A total of 1178 patients (951 ERA-I, 227 ERA-II) were eligible . A total of 390 patients died (367 ERA-I, 23 ERA-II), yielding a crude mortality rate of 33.1% . ERA-I group subjects were almost twice as likely to die as ERA-II group subjects, with a mortality risk ratio of 1.86 (95% confidence interval {CI}, 1.21 -2.86; P=.005) . After adjusting for Pneumocystis carinii and Mycobacterium avium prophylaxis use, AIDS diagnosis, CD4+ cell count, sex, and age, ERA-I participants were 1.93 times (95% CI, 1.25-2.97; P=.003) more likely to die than ERA-II participants . Among patients without AIDS when treatment was started, ERA-I participants were 2.50 times (95% CI, 1.59-3.93; P<.001) more likely to progress to AIDS or death than ERA-II participants . CONCLUSION: The HIV-infected individuals who received initial therapy with regimens including stavudine or lamivudine had significantly lower mortality and longer AIDS-free survival than those who received initial therapy with regimens limited to zidovudine, didanosine, and zalcitabine. J Infect Dis, 1998 Feb, 177(2), 515 - 8 TNP-470 is an effective antimicrosporidial agent; Coyle C et al.; Therapy for microsporidia, which cause diarrhea and a wasting syndrome in persons with AIDS, has had limited success . Fumagillin, a naturally secreted water-insoluble antibiotic, has in vitro activity against microsporidia and has been used successfully in the treatment of superficial keratitis in patients with AIDS, but systemic therapy has been limited by toxicity of the currently available fumagillin salt . TNP-470, a semisynthetic analogue of fumagillin, was studied in vitro and in the athymic nude mouse model of microsporidiosis . RK13 cells were infected with microsporidia of the family Encephalitozoonidae and treated at day 3 with TNP-470 . This agent was highly effective, with an ID50 (50% inhibitory dose compared with control) of 0.001 microg/mL . TNP-470 also demonstrated in vivo activity against Encephalitozoon cuniculi, with prolonged survival and the prevention of the development of ascites in infected athymic mice . These data suggest that the fumagillin derivative TNP-470 is a promising agent for the treatment of microsporidiosis. Int J Dermatol, 1997 Dec, 36(12), 923 - 5 Toxic epidermal necrolysis--a retrospective study; Criton S et al.; BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe, idiosyncratic, exfoliative disease of the skin and mucous membranes . The treatment of this condition is controversial . High-dose corticosteroid therapy has been the most commonly advocated treatment, but, more recently, this has changed to a no-steroid protocol . These conflicting treatments prompted us to evaluate retrospectively our protocol . METHODS: The patients admitted to the hospital from 1989 to 1995 with a clinical diagnosis of TEN were included in the study . These patients were given systemic steroids, prophylactic antibiotic, and supportive measures . RESULTS: The patients belonged to both sexes with an average age of 34 years . The average area of involvement was 85.62% . All the patients made an uneventful recovery without any evidence of sepsis . CONCLUSIONS: Treatment with systemic steroids is useful in the management of TEN, and there is no need for a burn care center. Mutat Res, 1997 Dec 5, 395(1), 9 - 27 A genetic system to detect mitotic recombination between repeated chromosomal sequences in Drosophila Schneider line 2 cells; Bartsch S et al.; In order to study mitotic homologous recombination in somatic Drosophila melanogaster cells in vitro and to learn more on the question how recombination is influenced by mutagens, a genetic system was developed where spontaneous and drug-induced recombination could be monitored . Two recombination reporter substrates were stably introduced in multiple copies into the genome of established D . melanogaster Schneider line 2 cells: one plasmid (pSB310) contained the 5' and 3' deleted neomycin phosphoribosyltransferase alleles neoL and neoR as direct repeats; the other (pSB485) contained similar deletions (lacZL and lacZR) of the beta-galactosidase gene (lacZ) . Restoration of a functional neo gene upon mitotic recombination between homologous sequences allowed direct selection for the event, whereas recombination in single cells harbouring the integrated lacZ-based reporter plasmid was detected by histochemical staining or flow cytometric analysis (FACS) . The neo-based construct in the clonal transgenic cell line 44CD4 showed a spontaneous recombination frequency of 2.9 x 10(-4), whereas the 485AD1 cell line harbouring the lacZ-based construct exhibited a frequency of 2.8 x 10(-4) . The alkylating agents EMS and MMS and the clastogen mitomycin C were able to induce recombination in the 485AD1 cell line in a dose-dependent manner . The results obtained from these studies suggest that the transgenic cell lines are potentially useful tools for identifying agents which stimulate direct repeat recombination in somatic Drosophila cells. Fukuoka Igaku Zasshi, 1997 Dec, 88(12), 389 - 94 Early appendectomy versus an interval appendectomy for appendiceal abscess in children; Handa N et al.; We retrospectively compared the results of an early appendectomy and an interval appendectomy at a later date after initial conservative treatment in children demonstrating perforated appendicitis with a localized abscess . The preoperative conditions were similar for both groups . The early group (n = 8) showed a statistically significant longer operation time and a greater but not significant blood loss were noted while a larger number of postoperative complications were also observed . On the other hand, in the late operation group (n = 6) initial conservative management including triple antibiotic therapy proved successful without the need to drain the abscess, and thus the interval appendectomy was safely completed without any complications . There were no significant differences between the two groups with respect to length of hospital stay or medical costs . Based on these findings, we thus recommend that initial conservative treatment followed by an interval appendectomy about three months later is a useful strategy for the treatment of appendiceal abscesses in children . However, whether or not an interval appendectomy is appropriate in all patients whose inflammation is suppressed with antibiotics still needs to be clarified. Food Chem Toxicol, 1997 Oct-Nov, 35(10-11), 1075 - 80 Lack of carcinogenicity of thiamphenicol in F344 rats; Kitamura T et al.; The carcinogenicity of thiamphenicol (TAP), an antibiotic drug, was examined in Fischer 344 rats of both sexes . TAP was given ad lib . in drinking water at levels of 0 (control), 125 or 250 ppm to groups of 50 male and 50 female rats for 2 yr . The treatment did not affect mortality and no toxic lesions were specifically induced . Furthermore, the incidence of tumours in the treated groups did not show any significant dose-related increase as compared with the control group . The results thus indicate that TAP is neither toxic nor carcinogenic, for any organs or tissues of F344 rats when given continuously at levels of 125 or 250 ppm in drinking water for 2 yr. Antibiot Khimioter, 1997, 42(11), 3 - 9 {Interaction of actinomycin D with suspended mycelium of streptomyces}; Orlova TI et al.; Binding of exogenous actinomycin D (AMD) by washed mycelium of streptomycetes i.e . variants of Streptomyces chrysomallus producing and not producing actinomycins and Streptomyces lividans not synthesizing the antibiotics was studied . Dependence of the bound quantity of AMD on its concentration, incubation time and temperature, energy source availability, influence of respiration inhibitors and the membranotropic antibiotic gramicidin S was shown . The intracellularly localized portion of the bound AMD likely penetrated to the cells by diffusion and was strongly bound presumably to DNA in the AMD sensitive S.lividans and to the specific intracellular actinomycin-binding proteins in the AMD resistant variants of S.chrysomallus . The ratio of AMD strongly bound by the mycelium and AMD easily washed with physiological solution and probably localized on the surface was determined . The ratio depended on sensitivity of the culture to AMD and for the variants of S.chrysomallus on the age of the culture and its ability to synthesize actinomycins. Antibiot Khimioter, 1997, 42(11), 10 - 4 {Isolation and partial characterization of NAD+ kinase from Streptomyces albogriseolus 444}; Ivanova IV et al.; NAD+ kinase was isolated from the culture of Streptomyces albogriseolus 444 . an organism producing an antibiotic complex . The enzyme was partially characterized . Its molecular weight is 141219 Da. Am J Infect Control, 1997 Dec, 25(6), 488 - 512 Infection prevention and control in the long-term-care facility . SHEA Long-Term-Care Committee and APIC Guidelines Committee; Smith PW et al.; More than 1.5 million residents reside in US nursing homes . In recent years, the acuity of illness of nursing home residents has increased . Long-term-care facility residents have a risk of developing nosocomial infection that is similar to acute-care hospital patients . A great deal of information has been published concerning infections in the long-term-care facility, and infection control programs are nearly universal . This position paper reviews the literature on infections and infection control program in the long-term-care facility, covering such topics as tuberculosis, bloodborne pathogens, epidemics, isolation systems, immunization, and antibiotic-resistant bacteria . Recommendations are developed for long-term-care infection control programs based on interpretation of currently available evidence . The recommendations cover the structure and function of the infection control program, including surveillance, isolation, outbreak control, resident care, and employee health . Infection control resources also are presented. Acta Orthop Scand, 1997 Dec, 68(6), 515 - 20 Exeter and charnley arthroplasties with Boneloc or high viscosity cement . Comparison of 1,127 arthroplasties followed for 5 years in the Norwegian Arthroplasty Register; Furnes O et al.; During the years 1991-1994, the Norwegian Arthroplasty Register recorded 1,324 primary hip arthroplasties implanted with the Boneloc cement . We have compared the survival until revision due to aseptic loosening for charnley (n 955) and Exeter (n 172) prostheses . The Boneloc cemented hips were also compared with high viscosity cemented hips implanted during the same period . In the Boneloc cemented group, the estimated probability of survival at 4.5 years of a Charnley femoral component was 74% and for an Exeter femoral component 97% (p < 0.0001) . Using a Cox regression model with adjustment for age, gender, type of cement, systemic antibiotic and stratified for diagnosis, an 8 times higher risk of revision was found in Boneloc cemented Charnley femoral components than in Exeter femoral components (p < 0.0001) . For the acetabular components, the difference between the Charnley and Exeter components with Boneloc cement was not statistically significant . In both the Charnley and the Exeter prostheses, the high viscosity cemented components had significantly better survival than the Boneloc cemented components . The Cox regression model showed that a Boneloc cemented Charnley femoral component had a 14 times higher risk of revision than a high viscosity cemented component (p < 0.0001), and for Exeter femoral components a 7 times higher revision risk was found in the Boneloc cemented components (p = 0.003) . Our results confirm the previously reported inferior results of Charnley prostheses implanted with Boneloc cement and inferior results of Boneloc cemented Exeter prostheses as well, but less pronounced than for Charnley prostheses. J Dent Assoc S Afr, 1996 Jun, 51(6), 359 - 63 Third molar surgical procedures: practices by maxillofacial and oral surgeons in South Africa; Naidoo LC; An audit of the treatment procedures routinely adopted by maxillofacial and oral surgeons for the removal of impacted third molars under general anaesthesia was undertaken in South Africa . Most maxillofacial and oral surgeons agree on the method of bone removal, the prescribing of antibiotics, analgesic agents and mouthwashes, the suturing of the incision wound and the post-operative review of patients . The results were compared to a similar study undertaken by Falcon and Roberts (1992) in the UK . With the exception of the method of bone removal, maxillofacial and oral surgeons in both groups share a similar approach to the treatment procedures adopted in the removal of impacted third molars . Some variability, however, existed in both studies with regard to the use of intra-operative local anaesthetic agents, the administration of peri-operative steroids and the use of non-steroidal anti-inflammatory agents. J Biol Chem, 1998 Jan 9, 273(2), 822 - 8 Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway; Soga S et al.; Activation of Ras leads to the constitutive activation of a downstream phosphorylation cascade comprised of Raf-1, mitogen-activated protein kinase (MAPK) kinase, and MAPK . We have developed a yeast-based assay in which the Saccharomyces cerevisiae mating pheromone-induced MAPK pathway relied on co-expression of K-Ras and Raf-1 . Radicicol, an antifungal antibiotic, was found to inhibit the K-ras signaling pathway reconstituted in yeast . In K-ras-transformed, rat epithelial, and K-ras-activated, human pancreatic carcinoma cell lines, radicicol inhibited K-Ras-induced hyperphosphorylation of Erk2 . In addition, the level of Raf kinase was significantly decreased in radicicol-treated cells, whereas the levels of K-Ras and MAPK remained unchanged . These results suggest that radicicol disrupts the K-Ras-activated signaling pathway by selectively depleting Raf kinase and raises the possibility that pharmacological destabilization of Raf kinase could be a new and powerful approach for the treatment of K-ras-activated human cancers. Biochim Biophys Acta, 1998 Jan 5, 1368(1), 19 - 26 Probing the water permeability of ROMK1 and amphotericin B channels using Xenopus oocytes; Sabirov RZ et al.; Water permeability of ion channels in the plasma membrane of Xenopus oocytes was studied by simultaneously measuring the membrane conductance under two-electrode voltage-clamp and the cell size by video-imaging technique . The basal level of osmotic water permeability of oocyte plasma membrane was 15.9+/-0.98 microm/s (SE, n = 5) . Extracellular application of pore-forming antibiotic amphotericin B at 5 microM developed macroscopic conductance of 995+/-70 microS (n = 5) and increased the osmotic water permeability of cell membrane by 44.9+/-4.1 microm/s . Meanwhile, after expressing ROMK1 channels, originally cloned from kidney, virtually no increase in the water permeability was observed even at the conductance level as high as 1113+/-47 microS (n = 5) . This result suggests that even though potassium channels, like any others, are considered to be water-filled pores, K+-selective ion-transporting pathway remains virtually water-impermeable in physiological conditions, such as in kidney epithelia where huge water transport takes place at both apical and basolateral sides. Orv Hetil, 1997 Nov 23, 138(47), 2999 - 3001 {Rule-based consultation systems}; Deutsch T et al.; This paper overviews the architecture of rule-based consultation systems and illustrates how such systems work by an Antibiotic Advisor . Knowledge representation and the inference engine implemented in the program are briefly described along with a sample consultation with the system . The paper is concluded with an analysis of the advantages and limitations of rule-based reasoning in clinical decision support. J Clin Microbiol, 1998 Jan, 36(1), 11 - 4 Evaluation of the indirect hemagglutination assay for diagnosis of acute leptospirosis; Levett PN et al.; Serology plays an important role in the diagnosis of leptospirosis . Few laboratories have the resources and expertise to perform the microscopic agglutination test . There is a need for rapid and simple serological tests which facilitate the early diagnosis of leptospirosis, while antibiotic therapy may be most effective . A commercially available indirect hemagglutination assay (IHA; MRL Diagnostics, Cypress, Calif.) was evaluated with multiple serum specimens from 107 patients being investigated for leptospirosis . By using a combination of enzyme-linked immunosorbent assay (ELISA) methods for immunoglobulin M (IgM) and IgG antibodies and the microscopic agglutination test, 54 patients were found to have leptospirosis and 53 were found not to have leptospirosis . The sensitivity of IHA for the detection of acute leptospirosis was 100%, the specificity was 94%, the positive predictive value was 95%, and the negative predictive value was 100% . IHA was negative when 13 antinuclear antibody-positive sera, 24 serum specimens from patients with syphilis, and 16 serum specimens false positive by the Venereal Disease Research Laboratory test were tested . IHA was shown to detect both IgM and IgG classes of antibodies in human sera . Serum specimens from 27 dogs investigated for leptospirosis were studied: 3 samples gave nonspecific hemagglutination, but for all remaining samples, the results of IHA and an IgM ELISA were concordant . Performance of IHA was simple, and IHA requires no specialized equipment . It represents a useful assay for laboratories which require a leptospiral diagnostic capability but lack the expertise to perform specialist investigations. Eur J Gastroenterol Hepatol, 1997 Nov, 9(11), 1091 - 5 Combination amoxycillin and metronidazole with famotidine in the eradication of Helicobacter pylori--a randomized, double-blind comparison of a three times daily and twice daily regimen; Goh KL et al.; OBJECTIVES: To determine the efficacy of a three times daily (t.i.d.) versus a twice daily (b.i.d.) regimen of combination amoxycillin and metronidazole and famotidine in the eradication of Helicobacter pylori and the influence of metronidazole resistance on the outcome of treatment . PATIENTS: Patients selected had unequivocal evidence of H . pylori infection based on the urease test, culture and histology and had either peptic ulcer disease or non-ulcer dyspepsia . DESIGN: The study was a comparative and double-blind study and patients were randomized to receive either amoxycillin 750 mg t.i.d . and metronidazole 500 mg t.i.d . for 12 days or amoxycillin 1000 mg b.i.d . and metronidazole 500 mg b.i.d . for 12 days . Both groups also received famotidine 40 mg for 6 weeks . MAIN OUTCOME MEASURE: Patients were assessed for successful eradication, defined as absence of bacteria in all tests, at least 4 weeks after completion of antibiotic therapy by repeat gastroscopy . RESULTS: One hundred and twenty-nine patients were recruited for the study . Two patients defaulted follow-up, two patients were withdrawn from the study and six patients were found to be non-compliant with medications . The eradication rates of the t.i.d . regimen was higher than the b.i.d . regimen (per protocol (PP) analysis: 83.3% (50/60) vs . 76.3% (45/59), P=0.337; intention-to-treat (ITT) analysis: 78.5% (51/65) vs . 75.0% (48/64), P=0.642) . Seventy-five patients had pre-treatment cultures checked for metronidazole resistance, 33 (44.0%) were found to be resistant . Acquired resistance occurred in 3/40 (7.5%) patients . Eradication rates of metronidazole-sensitive and metronidazole-resistant patients: t.i.d . regimen - 100% (17/17) and 88.2% (15/17), b.i.d . regimen - 19/21 (90.5%) and 11/15 (73.3%) . Side effects were reported in up to 70% of patients but were mild and tolerable in the majority . Two patients were withdrawn from the study because of a fixed drug eruption in one and generalized macular rash in the other . CONCLUSION: Combination amoxycillin and metronidazole is effective in eradicating H . pylori . There was a tendency for the t.i.d . regimen to be better than the b.i.d . regimen and for metronidazole-resistant infections to be associated with a lower eradication rate but these differences did not reach statistical significance. Ear Nose Throat J, 1997 Dec, 76(12), 870 - 1 Early postoperative otorrhea after tympanostomy tube placement: a comparison of topical ophthalmic and otic drops; Charnock DR; In a retrospective review of the incidence of early postoperative otorrhea, we compared cortisporin otic suspension with sulfacetamide/prednisolone ophthalmic drops and found them to be approximately equally effective . The beneficial effect of topical otic and ophthalmic antibiotic drops after tympanoplasty tube placement has already been well documented . It is therefore suggested that the potentially more comfortable and theoretically less ototoxic ophthalmic drop be used to decrease the incidence of early postoperative otorrhea. Rinsho Shinkeigaku, 1997 Sep, 37(9), 845 - 7 {A case of rapidly progressive T cell type malignant lymphoma which started with multiple cranial neuropathy}; Fukusako T et al.; A 35-year-old man had suffered from recurrent right trigeminal nerve palsy and flaccid paraparesis for about five months . Cerebrospinal fluid (CSF) showed a marked increase of protein (400 mg/dl) and mononuclear cells (146/mm3), but there were no malignant cells . Antibiotic therapy remitted his inguinal and mediastinal lymph nodes swelling, and trigeminal nerve palsy had recovered spontaneously . Then he developed left trigeminal and facial nerve palsy, mononeuropathy multiplex, and cauda equina syndrome . Nerve conduction studies revealed delayed velocity and reduction of amplitude . Enhanced magnetic resonance imaging showed increased signal intensity in bilateral trigeminal nerves, left internal auditory meatus, and meninges of the basal cistern . Also, there were two mass lesions in cauda equina . They were operated by orthopedist, and were not malignant . After that, CSF cells of malignant lymphoma were elevated and revealed T cell type (large cell) . Then the patient exacerbated in bulbar palsy and died . When there is lymph node swelling with multiple neurological deficits, despite remission of lesions and signs, biopsies should be positively pursued early in the patient's clinical course. Science, 1997 Dec 19, 278(5346), 2130 - 3 Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts; Schnieke AE et al.; Ovine primary fetal fibroblasts were cotransfected with a neomycin resistance marker gene (neo) and a human coagulation factor IX genomic construct designed for expression of the encoded protein in sheep milk . Two cloned transfectants and a population of neomycin (G418)-resistant cells were used as donors for nuclear transfer to enucleated oocytes . Six transgenic lambs were liveborn: Three produced from cloned cells contained factor IX and neo transgenes, whereas three produced from the uncloned population contained the marker gene only . Somatic cells can therefore be subjected to genetic manipulation in vitro and produce viable animals by nuclear transfer . Production of transgenic sheep by nuclear transfer requires fewer than half the animals needed for pronuclear microinjection. Chem Biol, 1995 Sep, 2(9), 575 - 9 Mitomycin C: small, fast and deadly (but very selective); Tomasz M; Mitomycin C, an important antitumor drug and antibiotic, has an extraordinary ability to crosslink DNA with high efficiency and absolute specificity for the sequence CpG . Recent results have shown how mitomycin C crosslinks DNA, and why the sequence specificity is so complete . This new understanding may allow the design of agents that mimic mitomycin C's economy of structure and can crosslink other sequences. Chem Biol, 1995 Jul, 2(7), 451 - 5 The proteolytic specificity of the natural enediyne-containing chromoproteins is unique to each chromoprotein; Zein N et al.; BACKGROUND: Enediyne chromoproteins are potent antitumor antibiotic agents . They consist of a labile nine-membered enediyne chromophore non-covalently associated with a stabilizing acidic polypeptide . Studies in vitro on three members of this superfamily of natural products--kedarcidin, maduropeptin and neocarzinostatin--demonstrated that their chromophores cleave DNA at sites specific to each chromophore . Recently, we showed that these chromoproteins possess proteolytic activity against histones in vitro, with histone H1 as a preferred substrate . Based on these results, we speculated that this selective proteolytic activity may be important in vivo in the delivery of the enediynes intact to the DNA in chromatin . RESULTS: We show here that each chromoprotein generates a unique set of H1 fragments as revealed by gel analyses of the H1 cleavage reaction products . To probe the observed cleavage specificity, we synthesized a 24-amino-acid peptide representing a basic region of histone H1 . This model peptide was incubated individually with similar concentrations of the kedarcidin, neocarzinostatin and maduropeptin chromoproteins as well as the kedarcidin apoprotein . The reaction products were analyzed by electrospray liquid chromatography/mass spectrometry . Our results indicate that all proteins cleave the peptide at selected backbone amides, and that these sites vary according to the chromoprotein used . Moreover, the kedarcidin apoprotein appears to be less specific than the kedarcidin chromoprotein complex . CONCLUSIONS: The small size, unique architecture and very acidic nature of the enediyne chromoproteins are highly unusual . These natural products exhibit the dual functionalities of specific DNA cleavage and selective proteolytic activity . This observation adds to the fascinating properties of these molecules and suggests that it is possible not only to design small moieties to cleave DNA but also to conceive of small proteins to deliver these moieties intact to defined areas of chromatin. Chem Biol, 1995 Apr, 2(4), 229 - 40 Hedamycin intercalates the DNA helix and, through carbohydrate-mediated recognition in the minor groove, directs N7-alkylation of guanine in the major groove in a sequence-specific manner; Hansen M et al.; BACKGROUND: The pluramycins are a class of antitumor antibiotics that exert their biological activity through interaction with DNA . Recent studies with the analog altromycin B have determined that these agents intercalate into the DNA molecule, position carbohydrate substituents into both major and minor grooves, and alkylate the DNA molecule by epoxide-mediated electrophilic attack on N7 of guanine located to the 3' side of the drug molecule . Alkylation is sequence dependent and appears to be modulated by glycoside substituents attached at the corners of a planar chromophore . The altromycin B-like analogs preferentially alkylate 5'AG sequences; hedamycin-like analogs prefer 5'TG and 5'CG sequences . Although the mechanism of guanine modification by altromycin B has been extensively studied, the mechanism of action of hedamycin has not been previously determined . RESULTS: Using high-field NMR, we have shown that hedamycin stacks to the 5' side of the guanine nucleotide at the site of intercalation in a DNA decamer, positioning both aminosaccharides into the minor groove to direct alkylation by the epoxide moiety on N7 of guanine . The C10 linked N,N-dimethylvancosamine sugar moiety interacts to the 5' side of the intercalation site, while the C8 linked anglosamine moiety interacts to the 3' side . The binding interactions of the two aminosugars steer the C2 double epoxide located in the major groove into the proximity of N7 of guanine . Unexpectedly, it is not the first epoxide that undergoes electrophilic addition to N7 of guanine, which would correspond to altromycin B, but the second, terminal epoxide . CONCLUSIONS: We have used two-dimensional NMR to elucidate the sequence-selective recognition of DNA by hedamycin and the mechanism of covalent modification of guanine by this antibiotic . Characterization of the intermolecular interactions between both hedamycin and altromycin B and their targeted DNA sequences has yielded a better understanding of the reasons for variations in sequence selectivity and alkylation reactivity among the pluramycin compounds. Rocz Panstw Zakl Hig, 1997, 48(2), 173 - 8 {Determination of natamycin residues in ripening cheeses by high-performance liquid chromatography}; Rybinska K et al.; The purpose of the study was to determine the usefulness of high performance liquid chromatography (HPLC) for natamycin determination in routine control of ripening cheeses . In the method the antibiotic is extracted from the studied sample with a 2:1 methanol/water solution, freezing of contaminants at -18 degrees C and determination of HPLC using a RP C8 column and UV detection . In case of low concentrations of the antibiotic the extract was condensed by extraction to solid phase (SPE) . In the study of the fortified samples the basic analytical parameters of the method were tested (determinability, repeatability, recovery) and its usefulness in the 0.05-0.4 mg/kg concentration range (by SPE) and above 0.5 mg/kg of cheese was checked . Recovery was from 87 to 98%, repeatability was 1.3-7.3% and determinability was 0.5 mg/kg (using SPE 0.05 mg/kg) . The obtained results demonstrated a good usefulness of HPLC for routine control of natamycin content in ripening cheeses . It seems recommendable to apply HPLC for natamycin determination in ripening cheese by sanitary-epidemiological stations. Przegl Lek, 1997, 54(5), 365 - 6 {Left sided subphrenic abscess of unknown origin}; Kleba T et al.; The authors present case of 60 years old male with subphrenic abscess . The patient had been threefold open abdomen, and cause of subphrenic abscess remain unknown . The authors think, that best treatment are: transperitoneal lavage drainage and antibiotic therapy. Med Clin (Barc), 1997 Sep 27, 109(10), 361 - 3 {Direct pharmaceutical costs, diagnostic related groups and CD4 cell count in hospitalized HIV-infected patients}; Serrais J et al.; BACKGROUND: To estimate the direct pharmaceutical costs of the HIV-infected patients admitted in the HCP, the variability and the relation between CD4 cell count . PATIENTS AND METHODS: We collected for each patient admitted to Department of infectious Diseases between 1/1/93 to 12/12/94 the direct pharmaceutical cost for GRD and diagnosis discharge . Also we collected the lymphocyte CD4 cell count . RESULTS: The number of patients observed was 877 and the total pharmaceutical cost was 65,756,751 pts., 24,900,827 pts . were spent in antibiotic drugs and 22,225,273 pts . in antiviral drugs (non anti-HIV included) . 568 patient had CD4 cell count on admission . 75% of them had a CD4 cell count less than 50 x 10(4)/l . The variability of the pharmaceutical cost estimated in the GRD 489, 490 and diagnosis discharge was higher than 150% . There was not lineal correlation between the total costs and the CD4 cell count . The mean direct pharmaceutical costs in patients with CD4 cell count less than 60 x 10(6)/l was greater than in the others . CONCLUSIONS: Antibiotic and antiviral drugs accounted for the 72% of global pharmaceutical cost in HIV patients admitted . The variability observed in the GRD 489 and 490 was high . The direct pharmaceutical costs were conditioned by the lymphocyte CD4 cell count because this parameter determine the type of infections disease that these patients suffered. Klin Monatsbl Augenheilkd, 1997 Aug, 211(2), 101 - 5 {Intraocular pressure after extracapsular cataract extraction with posterior chamber lens implantation--sulcus versus capsular bag fixation}; Kampmeier J et al.; BACKGROUND: In this retrospective study the postoperative alteration of intraocular pressure after cataract extraction and posterior chamber lens implantation was analyzed statistically . The influence on intraocular pressure between different positions of the loops (sulcus versus bag) was compared . PATIENTS AND METHOD: The posterior chamber lens implantation was performed on 267 eyes with 129 sulcus implanted and 138 in-the-bag implanted intraocular lenses . The average age of the patients was 74.8 respectively 71.9 years, with an equal ratio of sex . In surgery the viscoelastic experimentation of the nucleus was done via corneoscleral cut . A x-crossed suture sealed the corneoscleral wound followed by subconjunctival injection of corticosteroids . The postoperative medication for 4-6 weeks consisted of a corticosteroid and antibiotic combination . RESULTS: The average intraocular pressure of the sulcus implanted respectively in the bag implanted intraocular lenses increased from 15.4 mm Hg respectively 15.9 mm Hg preoperatively to 16.3 respectively 15.8 mm Hg at the first postoperative day . After two months the intraocular pressure decreased to 14.6 respectively 14.1 mm Hg . That means a pre- to postoperative difference of -0.8 respectively -1.8 mm Hg . CONCLUSIONS: In summary both groups showed a slight decrease in average intraocular pressure after two months . In comparison to the sulcus implanted intraocular lens the decrease of intraocular pressure was more than 1 mm Hg in case of the in the bag implanted lens . This decrease was statistically significant but may be considered of less clinical interest. Fortschr Med, 1997 Aug 20, 115(22-23), 41 - 3 {Heart failure after myocardial infarct in decompensated diabetes mellitus . Acute therapy with catecholamines--long-term therapy with ACE inhibitor-loop diuretic combination}; Brilla CG; In a 63-year-old woman with longstanding type I diabetes mellitus, CAD and chronic heart failure, a subacute myocardial infarction developed, together with decompensation of cardiac function and diabetes and concurrent pneumonia . Acute heart failure with acute renal failure on top of diabetic nephropathy, and interstitial pulmonary edema was initially treated with hemofiltration and catechol amines together with antibiotic and perfusor-regulated insulin therapy, and systemic heparinization . Subsequent chronic treatment with digitalis, acetyl salicylic acid, insulin and a combination of an ACE inhibitor and a loop diuretic resulted in an improvement of heart failure to NYHA functional class II where PTCA of coronary multi-vessel disease could be performed with low risk. Pol Merkuriusz Lek, 1997 Apr, 2(10), 291 - 4 {Supportive (antiinflammatory) treatment of bacterial meningoencephalitis with dexamethasone}; Szychowska Z; With improved understanding of the pathophysiology of bacterial meningitis, a number of points in the deleterious inflammatory cascade have been identified as possible sites for modulation . Dexamethasone attenuates tissue injury by inhibiting host mediators at several steps in the inflammatory process . Animal and clinical trials have demonstrated that adjunctive corticosteroid therapy reduces the production of cytokines in the CSF . This results in decreased severity of the inflammatory process and fewer neurologic sequelae . However, routine use of steroids adjunctive treatment of bacterial meningitis remains controversial . Data support the use of adjunctive corticosteroid therapy in children with S . pneumoniae and H . influenzae type b meningitis . There is not sufficient evidence supporting the use of adjunctive corticosteroid therapy in patients with meningitis caused by N . meningitidis, which is the main cause of purulent meningitis in Poland . Also, the routine use of the dexamethasone in children and adult meningitis in Poland cannot presently be recommended . When using dexamethasone timing and dosage seems to be crucial . Administration before or with antibiotics is optimal for attenuating the subarachnoid space inflammatory response . The host's inflammatory response can be accompanied by the neuroendocrine response which is complex and its mediators are not well understood . Data indicate that the large component of the neuroendocrine response (e.g . inadequate secretion of ADH and large adrenocortical stress response) adversely affects the outcome from bacterial meningitis . So, the modulating effect of dexamethasone on both inflammatory and neuroendocrine response may be beneficial in bacterial meningitis and can probably be, achieved with sufficiently high dose of dexamethasone w has not yet been specified . Based on present pathophysiological and pharmacokinetic data, and to achieve maximum benefits and minimum complications, dexamethasone therapy started 10 min before the first dose of antibiotic and given every 12 h for only 2 days in a dose 0.8 mg/kg/day is suggested . Future studies of the pathogenesis and pathophysiology of bacterial meningitis may lead to the development of other adjunctive treatment strategies, improving the outcome of this serious disease. Klin Khir, 1997, (3-4), 80 - 1 {Current treatment aspects of postoperative peritonitis}; Shapryns'kyi VO; Treatment of postoperative peritonitis includes correction of enteral insufficiency, application of programmed relaparotomy, sanation and drain of abdominal cavity, antibiotic therapy, methods of detoxication . Complex approach promotes improvement of results treatment and diminution of postoperative lethality. Vestn Ross Akad Med Nauk, 1997, (2), 12 - 6 {New approaches to the diagnosis and treatment of inflammatory diseases of the adnexa uteri}; Savel'eva GM et al.; The paper summarizes follow-ups of 2500 patients with inflammatory diseases of the uterine appendages, provides evidence for the benefits of laparoscopic diagnosis and treatment of all types of this condition, which makes it possible to verify the diagnosis and perform less traumatic organ-sparing operations . To use combined antiinflammatory antibiotic therapy in view of the etiology of inflammation, as well as immunomodulators is the requisite condition for treating acute types of a disease . The new approaches to the diagnosis and treatment of inflammatory diseases of the uterine appendages substantially improved therapeutical outcomes and maintained female reproductive function. Ophthalmologe, 1997 Aug, 94(8), 591 - 4 {Acute Borrelia infection . Unilateral papillitis as isolated clinical manifestation}; Pradella SP et al.; BACKGROUND: Borrelia burgdorferi is the cause of erythema chronicum migrans and Lyme disease . Ticks like Ixodes ricinus are responsible for transmission . Frequently, the tick bite is not noticed by the patient . Eye manifestations, such as keratoconjunctivitis, scleritis, chronic uveitis, vitritis, chorioretinitis, optic nerve disease, orbital myositis and paresis of the eye muscles, often occur after a long period of time and vary greatly . PATIENTS AND METHODS: We present below the case reports of a man 38 years old and a woman of 31, each with manifestation of an ocular Borrelia infection (papillitis and panuveitis, respectively) . RESULTS: By antibody-screening with the ELISA technique and Western Blot analysis we were able to prove the serological infection . After specific antibiotic therapy, ocular inflammation improved rapidly, as did visual acuity . The papillitis only healed partially . CONCLUSIONS: In case of therapy-resistant inflammation of the eye we have to exclude general infections because cortisone therapy alone may result in worsening the condition . VECP can be used effectively in the differential diagnosis of papilloedemas . Early diagnosis and therapy of an acute Borrelia infection restrict the extent of the lesions and prevent ocular and general late manifestations . Seronegative values in subjects strongly suspected of having Lyme disease do not necessarily exclude the diagnosis of Lyme disease. An Med Interna, 1997 Aug, 14(8), 419 - 24 {Pneumonia and pleural effusion . Therapeutic management}; Jurado Gamez B; The pleural effusion with pneumonia is a common complication . Early diagnosis and adequate handling are required, being based fundamentally on the characteristics of pleural liquid . Antibiotic therapy and pleural drainage are, in most cases, the main basis for very best outcome . Un specific circumstances administration of intrapleural fibrinolysis is increased, giving up surgery for those difficult cases which are not resolved with the previous treatment . The clinical case and the therapeutical different choices are revised, and finally a guideline that helps to the best management of parapneumonic effusion, is suggested. Biochemistry, 1997 Oct 21, 36(42), 12653 - 9 Calicheamin-mediated DNA damage in a reconstituted nucleosome is not affected by histone acetylation: the role of drug structure in the target recognition process; Liang Q et al.; We have examined the role of drug structure and histone acetylation in DNA damage produced by the enediyne antibiotic calicheamicin gammaII in nucleosomes reconstituted onto the 5S rRNA gene of Xenopus borealis . Consistent with previous observations, calicheamicin damage at the 3'-end of a purine tract (positions -13 and -14) was enhanced in the nucleosome compared to the naked DNA while damage at other sites was somewhat reduced in the nucleosome . However, damage produced by esperamicin C, an analog of calicheamicin missing the terminal sugar-aromatic ring in the side chain, showed no enhancement at positions -13 and -14, and its sequence selectivity in naked DNA was markedly different from that of calicheamicin . This highlights the importance of the intact tetrasaccharide side chain in the recognition of the structural deformation occurring at the 3'-ends of purine tracts . Both drugs produced identical cleavage patterns in normal and hyperacetylated nucleosomes . Given the sensitivity of calicheamicin to local DNA conformation, this observation is consistent with other studies that suggest that histone acetylation alone does not significantly affect the local conformation of core DNA in the nucleosome. Transplantation, 1998 Jan 27, 65(2), 199 - 203 Causes of leukocytosis in liver transplant recipients: relevance in clinical practice; Singh N et al.; BACKGROUND: Leukocytosis without a recognizable etiology often poses a diagnostic and therapeutic dilemma in transplant recipients . METHODS: Fifty consecutive episodes of leukocytosis in 47 liver transplant recipients were prospectively assessed . RESULTS: Leukocytosis was documented in 70% (33/47) of the patients, whereas 30% (14/47) of the patients never developed leukocytosis . Three distinctive etiologies accounted for 82% of the episodes . Thirty-two percent (16/50) of the episodes occurred between 1 and 3 days after transplantation, were unaccompanied by fever, and resolved spontaneously within 2 days . Infections accounted for 28% (14/50) of the episodes of leukocytosis; median time to onset was 25 days after transplantation, and fever occurred in 57% . In 22% (11/50) of the episodes, a characteristic leukocytosis occurred 7-14 days after transplantation (in the absence of documented infections or rejection) that was unaccompanied by fever, and resolved spontaneously without antibiotics; the platelet count of these patients was significantly higher than those of postoperative (P < 0.01) or infectious leukocytosis (P < 0.05) . Resolution of pretransplant hypersplenism, with the release of sequestered splenic granulocytes and platelets, was the likely cause . Rejection and corticosteroid boluses accounted for 4% and 8% of the episodes, respectively . CONCLUSIONS: Timing of onset and awareness of the patterns of leukocytosis can be valuable in the evaluation of posttransplant leukocytosis . Stable patients with leukocytosis, but without fever or documented infections, in the immediate postoperative period and between 7 and 14 days after transplantation, need not be empirically treated with antibiotics. J Bacteriol, 1998 Feb, 180(3), 605 - 13 Specific in vivo labeling of cell surface-exposed protein loops: reactive cysteines in the predicted gating loop mark a ferrichrome binding site and a ligand-induced conformational change of the Escherichia coli FhuA protein; Bos C et al.; The FhuA protein of Escherichia coli K-12 transports ferrichrome, the antibiotic albomycin, colicin M, and microcin 25 across the outer membrane and serves as a receptor for the phages T1, T5, phi80, and UC-1 . FhuA is activated by the electrochemical potential of the cytoplasmic membrane, which probably opens a channel in FhuA . It is thought that the proteins TonB, ExbB, and ExbD function as a coupling device between the cytoplasmic membrane and the outer membrane . Excision of 34 residues from FhuA, tentatively designated the gating loop, converts FhuA into a permanently open channel . FhuA contains two disulfide bridges, one in the gating loop and one close to the C-terminal end . Reduction of the disulfide bridges results in a low in vivo reaction of the cysteines in the gating loop and no reaction of the C-terminal cysteines with biotin-maleimide, as determined by streptavidin-beta-galactosidase bound to biotin . In this study we show that a cysteine residue introduced into the gating loop by replacement of Asp-336 displayed a rather high reactivity and was used to monitor structural changes in FhuA upon binding of ferrichrome . Flow cytometric analysis revealed fluorescence quenching by ferrichrome and albomycin of fluorescein-maleimide bound to FhuA . Ferrichrome did not inhibit Cys-336 labeling . In contrast, labeling of Cys-347, obtained by replacing Val-347 in the gating loop, was inhibited by ferrichrome, but ferrichrome quenching was negligible . It is concluded that binding of ferrichrome causes a conformational change of the gating loop and that Cys-347 is part of or close to the ferrichrome binding site . Fluorescence quenching was independent of the TonB activity . The newly introduced cysteines and the replacement of the existing cysteines by serine did not alter sensitivity of cells to the FhuA ligands tested (T5, phi80, T1, colicin M, and albomycin) and fully supported growth on ferrichrome as the sole iron source . Since cells of E . coli K-12 display no reactivity to thiol reagents, newly introduced cysteines can be used to determine surface-exposed regions of outer membrane proteins and to monitor conformational changes during their function. J Am Board Fam Pract, 1998 Jan-Feb, 11(1), 41 - 5 Bronchiolitis obliterans organizing pneumonia mimicking community-acquired pneumonia; Ward E et al.; BACKGROUND: Bronchiolitis obliterans organizing pneumonia is a rare disease that mimics infectious pneumonia . Most patients respond well to corticosteroid therapy . METHODS: We report a single case and findings from an English language literature search of MEDLINE using key words "bronchiolitis obliterans organizing pneumonia." RESULTS AND CONCLUSIONS: Bronchiolitis obliterans organizing pneumonia should be considered when a patient with pneumonia does not respond to antibiotics and has multiple patchy infiltrates and characteristic bronchoalveolar lavage patterns . A tissue sample is required for definitive diagnosis . Infection by a multiresistant organism can occur with multiple antibiotic therapy and concomitant use of corticosteroids, particularly when no initial infecting organism is identified. Clin Rheumatol, 1997 Nov, 16(6), 617 - 22 Case report and review of the literature . Fatal pulmonary complication in ankylosing spondylitis; Strobel ES et al.; A 44-year-old non-smoking patient with longstanding ankylosing spondylitis presented in marked respiratory distress with tachypnea, fever, cough, greenish sputum, night sweats, dyspnea and weight loss . Computed tomography showed traction bronchiectases and cavities associated with scarring . The findings were most pronounced in the upper lobes which contained multiple cavities up to 8 cm in diameter harboring fungus balls . The superior segment of the left lower lobe showed two additional cavities . Tuberculosis and atypical mycobacteria were ruled out . Antibiotic therapy resulted in transient improvement . Five months after this acute exacerbation the patient expired from massive haemoptysis . Pulmonary fibrosis is a rare manifestation of ankylosing spondylitis, may be complicated by infection and haemorrhage and determine the dismal prognosis of these patients. Comput Nurs, 1998 Jan-Feb, 16(1), 37 - 44 Development and evaluation of a computer-assisted instruction package in clinical pharmacology for nursing students; Gee PR et al.; Recent reports commissioned by the Australian Government have highlighted the need to improve medication use in both community and hospital settings . Nurses are placed ideally to promote safe and effective drug use . The aim of this project was to develop and evaluate a computer-assisted instruction package, to help undergraduate nursing students improve their knowledge of clinical pharmacology, and to enhance their ability to contribute to the quality use of medications . In a collaborative project, staff of the Tasmanian Schools of Pharmacy and Nursing have produced the program PharmaCAL, using HyperCard 2.2 for the Apple Macintosh . A wide range of clinical pharmacology units are covered extensively, concentrating on drugs in common use and based on body systems: cardiovascular pharmacology (including hypertension, cardiac failure and angina); respiratory pharmacology; alimentary tract pharmacology (including peptic ulcer, diarrhea, and constipation); central nervous system pharmacology (analgesia, anxiety and insomnia, depression, psychoses, and epilepsy); antibiotic chemotherapy; and diabetes mellitus . Many color illustrations have been included . Each unit has a set of multiple choice questions to provide feedback to students . The package was evaluated in two ways . First, a questionnaire was used to assess users' opinions of the package . Second, a validated multiple choice test on clinical pharmacology and therapeutics was administered to 24 third-year nursing students before and after a set of sessions using the package and to a control group of 28 nursing students who were not exposed to the PharmaCAL package . The package generally was well received by the nursing students . Clinical pharmacology test scores significantly improved after using the package and were significantly higher than for the control group of students . The program is a useful adjunct to the existing nursing curriculum . It also could be used in postgraduate nursing education and other health sciences. Avian Dis, 1997 Oct-Dec, 41(4), 802 - 7 Efficacy of tilmicosin in the control of experimental Mycoplasma gallisepticum infection in chickens; Kempf I et al.; This study was conducted to evaluate the efficacy of 5-day, "in water" tilmicosin medication for the prevention of experimental Mycoplasma gallisepticum (MG) disease in 10-day-old specific-pathogen-free (SPF) chickens . Birds were inoculated intratracheally and into the sinus with the MG R-P10 strain . A limited dose titration of the antibiotic over the expected effective range was included, using six groups of 60 birds each: UI: uninfected untreated group; IUT: infected untreated group; IT1 to IT4: four infected treated groups, which were administered 50, 100, 200, or 300 mg/liter of tilmicosin . The birds were given tilmicosin from 8 to 13 days of age and were inoculated at 10 days of age . The birds were observed for 11 days postchallenge before terminal postmortem examination was completed including, assessment of lesions and sampling for mycoplasma culture and serology . Body-weight gains of the different groups were compared . The results showed that tilmicosin medication at dose levels of 50-300 mg/liter significantly decreased growth losses and respiratory signs due to MG infection (P < 0.05) . Significant reduction in air sac and peritonitis lesions were obtained by treatment with 100, 200 or 300 mg/liter for 5 days (P < 0.05) . A significant reduction in the proportion of MG-culture-positive birds was obtained at a dose level of 50 mg/liter (P < 0.05) . Increasing the dose resulted in a further decrease in the number of MG shedding chickens to the extent that with the two highest doses of tilmicosin, no bird was serologically positive on day 21, compared to 46/58 positively infected untreated birds (day 21). Anaesth Intensive Care, 1997 Dec, 25(6), 637 - 9 Infection in central lines: antiseptic-impregnated vs standard non-impregnated catheters; Loo S et al.; We report a survey of 196 consecutive central venous catheters (CVCs) placed in 151 patients in the Intensive Care Unit (ICU) over a ten-month period . Over this time the use of a new antiseptic-impregnated triple lumen CVC (Arrowgard Blue, Arrow International Inc., Pennsylvania, U.S.A.) was alternated on a bimonthly basis with the standard triple-lumen CVC (Arrow International Inc., Pennsylvania, U.S.A.) . The overall rate of CVC tip infection was lower in the impregnated CVC group (15.6% vs 30.9%, P < 0.05) . The impregnated CVC group had a much lower cumulative infection rate when the dwell time in patients was five days or less (3.3% vs 26.9%, P < 0.05) . However, the difference between the cumulative infection rate was not statistically significant (P > 0.05) for dwell times of 6, 7 or 8 days respectively . There was no difference in the CVC related bacteraemia rates between the two groups (3.9% vs 3.7%, P > 0.05). Clin Infect Dis, 1997 Dec, 25(6), 1303 - 9 Staging and staging application in osteomyelitis; Mader JT et al.; Osteomyelitis is traditionally staged by the Waldvogel classification system . The Waldvogel classification is an etiologic system and does not readily lend itself to guiding surgical or antibiotic therapy . Other classifications have been developed to emphasize different clinical aspects of osteomyelitis . These classifications include those of Ger, Kelly, Weiland, Gordon, May, and Cierny-Mader . The Cierny-Mader classification is based on the anatomy of bone infection and the physiology of the host . The Cierny-Mader classification permits the development of comprehensive treatment guidelines for each stage . The Cierny-Mader classification is used to demonstrate the application of staging for the diagnosis and treatment of osteomyelitis. Clin Infect Dis, 1997 Dec, 25(6), 1295 - 302 Experimental models of bone and prosthetic joint infections; Cremieux AC et al.; Bone and joint infections are difficult to cure . The difficulty is related to the presence of bacteria adherent to foreign material in many cases and also to the limited activity of antibiotics in infected bones . Clinical trials are difficult to design because of the heterogeneity of the disease and the number of factors that could influence the therapeutic response . To control for these multiple variables, attempts have been made to develop reliable animal models of osteomyelitis and prosthetic joint infections that closely mimic the different infections seen in orthopedic surgery and that allow evaluation of the efficacy of surgical procedures as well as local or systemic antibiotic therapy . These models will continue to provide us information on the pathogenesis and management of such infections. Pharmacol Res, 1997 Sep, 36(3), 249 - 54 'In vitro' interactions of monensin with hepatic xenobiotic metabolizing enzymes; Ceppa L et al.; Monensin, a polyether ionophore antibiotic used worldwide for its anticoccidial and growth-promoting properties, is reported to act as anin vivo inducer or inhibitor of drug-metabolizing enzyme systems in various species according to dosage regimens and duration of exposure . When incubated at a concentration up to 0.25 mM with hepatic subfractions from either untreated- (UT) or phenobarbital- (PB) induced rats, monensin did not induce appreciable changes in cytochrome P450 content and functions as well as in NADPH cytochrome c reductase or glutathione S-transferase . On the other hand, monensin concentrations ranging from 0.05 to 0.25 mM proved to increase the initial rate of NADPH oxidation up to 63% in UT-microsomes, and the in vitro addition of the ionophore to microsomes resulted in the formation of a characteristic type I binding spectrum . The rate of monensin O-demethylation was 0.34+/-0 . 01 and 0.99+/-0.07 nmol min-1 per mg of protein in UT- and PB-microsomes, respectively . In the latter, this reaction was consistently depressed when NADPH was omitted or replaced with NADH, or upon the addition of 1 mM metyrapone, a known P450 inhibitor . It is concluded that monensin does not behave as a direct in vitro inhibitor of drug metabolizing enzymes and appears to be a substrate of P450-dependent monooxygenases . J Ind Microbiol Biotechnol, 1997 Nov-Dec, 19(5-6), 369 - 77 Enzymatic synthesis of diastereospecific carbacephem intermediates using serine hydroxymethyltransferase; Kreuzman AJ et al.; The serine hydroxymethyltransferase (SHMT) gene glyA was over-expressed in Escherichia coli and the enzyme was purified to near homogeneity . Reaction conditions for E . coli and rabbit liver SHMTs were optimized using succinic semialdehyde methyl ester (SSAME) and glycine . The catalytic efficiency (kcat/K(m)) of E . coli SHMT for SSAME was 2.8-fold higher than that of rabbit liver enzyme . E . coli SHMT displayed a pH-dependent product distribution different from that of rabbit liver enzyme . For the pyridoxal-5'-phosphate (PLP)-dependent reaction, E . coli and rabbit liver SHMTs showed a high product diastereospecificity . The stoichiometric ratio of PLP to the dimeric E . coli SHMT was 0.5-0.7, indicating a requirement for external PLP for maximal activity . Using SSAME or its analog at a high temperature, E . coli SHMT mediated efficient condensation via a lactone pathway . In contrast, at a low temperature, the enzyme catalyzed efficient conversion of 4-penten-1-al via a non-lactone mechanism . Efficient conversion of either aldehyde type to a desirable diastereospecific product was observed at a pilot scale . E . coli SHMT exhibited a broad specificity toward aldehyde substrates; thus it can be broadly useful in chemo-enzymatic synthesis of a chiral intermediate in the manufacture of an important carbacephem antibiotic. Int J Biochem Cell Biol, 1997 Nov, 29(11), 1235 - 9 Melanin; Riley PA; Melanin is an irregular light-absorbing polymer containing indoles and other intermediate products derived from the oxidation of tyrosine . Melanin is widely dispersed in the animal and plant kingdoms . It is the major pigment present in the surface structures of vertebrates . The critical step in melanin biogenesis is the oxidation of tyrosine by the enzyme tyrosinase . In vertebrates this enzyme is active only in specialized organelles in retinal pigment epithelium and melanocytes . In mammals melanin is formed as intracellular granules . Melanin granules are transferred from melanocytes to epithelial cells and form the predominant pigment of hair and epidermis . Melanin has many biological functions . Reactive quinone intermediates in the melanin biosynthetic pathway exhibit antibiotic properties and the polymer is an important strengthening element of plant cell walls and insect cuticle . Light absorption by melanin has several biological functions, including photoreceptor shielding, thermoregulation, photoprotection, camouflage and display . Melanin is a powerful cation chelator and may act as a free radical sink . Melanin is used commercially as a component of photoprotective creams, although mainly for its free radical scavenging rather than its light absorption properties . The pigment is also a potential target for anti-melanoma therapy. Eur J Haematol, 1998 Jan, 60(1), 1 - 6 The management of crisis in sickle cell disease; Okpala I; The symptoms and signs of sickle cell disease are exacerbated in times of crisis, characterized by tissue infarction or worsening anaemia . Prompt medical intervention is required in these distressing situations to provide relief and comfort to the patient . Effective analgesia is crucial in treating the painful crisis of sickle cell disease . The haemoglobinopathy may cause hyposthenuria with reduced ability to excrete the sodium load in normal saline . A 5% dextrose solution or 5% dextrose in 25% normal saline is therefore recommended for intravenous hydration . As the leading cause of morbidity and mortality in sickle cell disease, infections call for vigorous antibiotic therapy . Oxygen administration should be reserved for hypoxic patients, and blood transfusion given only when really indicated . Acute chest syndrome and cerebrovascular accidents are life-threatening complications of sickle cell disease whereas priapism can cause important long-term sequelae; all deserve urgent attention . In the long term, comprehensive care is cost-effective in reducing the frequency and adverse effects of sickle cell crisis. Community Nurse, 1997 May, 3(4), 25 - 6 Mould spores: the unusual suspects in hay fever; Cross S; Microfungi are microscopic plants that lack chlorophyll and depend on plant or animal material for nourishment . Moulds will only proliferate in a humid atmosphere . Moulds produce vast numbers of small spores, varying in diameter from 2 to 5 microns, which become airborne . Some common moulds in the UK include Cladosporium, Alternaria and Aspergillus, of which several species are pathogenic to humans . The frequency of mould allergy is uncertain, but it appears to be higher in children than in adults . Wet weather favours mould growth, and sunny, windy weather favours spore release, while snow reduces both considerably . In warm, humid climates, fungi are present in large quantities all the year round . In temperate zones, spore counts are highest during the late summer . Indoor exposure largely depends upon the level of humidity . Mould growth can be immense in badly constructed houses and can contribute to sick-house syndrome . Occupational exposure can occur during manufacture of bread, cheese, beer and wine . In recent years, the use of moulds has been extended to include antibiotic, enzyme and steroid manufacture . Inhalation of small quantities of mould spores can evoke an IgE response and asthma . Massive exposure to some moulds growing in the airway can evoke an IgE and IgG response in people with bronchopulmonary aspergillosis . The inhalation of large amounts of mould antigen in organic dust can cause an IgG response and extrinsic allergic alveolitis J Thorac Cardiovasc Surg, 1998 Jan, 115(1), 63 - 8; discussion 68-9 Aggressive surgical management in localized pulmonary mycotic and nonmycotic infections for neutropenic patients with acute leukemia: report of eighteen cases; Baron O et al.; OBJECTIVE: To prevent hemoptysis and relapse during subsequent chemotherapy-induced neutropenia in patients with localized forms of invasive pulmonary aspergillosis, we adopted an aggressive surgical approach . METHODS: From 1988 to 1996, 18 patients with hematologic diseases were referred with the diagnosis of localized invasive pulmonary aspergillosis . The diagnosis was based on clinical features, failure to respond to antibiotic therapy, an air crescent sign suggestive of aspergillosis on the computed tomographic scan (39%), and retrieval of fungi by bronchoalveolar lavage (44%) . RESULTS: The following procedures were done: one pneumonectomy, four bilobectomies, seven lobectomies, six wedge resections, and one lobectomy with wedge resection (one patient had two procedures) . No perioperative deaths or complications occurred . The histologic examination confirmed the diagnosis of invasive pulmonary aspergillosis in 12 patients . The six other diagnoses were as follows: one case of classic aspergilloma, one case of pneumonia, and four cases of pulmonary abscess . According to univariate analysis, thoracic pain was less common in the group with noninvasive pulmonary aspergillosis (1/6) than in the group with invasive pulmonary aspergillosis (8/12) (p < 0.05) . Sixteen patients required subsequent hematologic treatments . Sixty-six percent of the patients are alive with a mean follow-up of 29.1 +/- 27.8 months (range 2 to 103 months), with no statistically significant difference between the invasive and the noninvasive pulmonary aspergillosis groups . Five patients died of a recurrence of their malignant disease at a mean of 17.2 +/- 12.5 months (range 2 to 30 months), and one had a cerebral recurrence of Aspergillus infection during a bone marrow transplantation 3 months later . CONCLUSION: Aggressive surgical management radically improves the prognosis of invasive pulmonary aspergillosis, even if the surgical indications include some nonmycotic infections because of the difficulty in establishing the clinical diagnosis. Biol Blood Marrow Transplant, 1997 Nov, 3(5), 273 - 81 Comparison of retroviral-mediated gene transfer into cultured human CD34+ hematopoietic progenitor cells derived from peripheral blood, bone marrow, and fetal umbilical cord blood; Campain JA et al.; Genetic alteration of stem cells ex vivo followed by bone marrow transplantation could potentially be used in the treatment of numerous diseases and malignancies . However, there are many unanswered questions as to the best source of hematopoietic cells for long-term reengraftment and the most effective way to introduce foreign genes into this target cell . We have compared retroviral-mediated gene transfer into CD34+-enriched cells derived from peripheral blood (PB), bone marrow (BM), or fetal umbilical cord blood (CB) . Cells from all three sources that had been expanded ex vivo in the presence of stem cell factor (SCF), interleukin-3 (IL-3), IL-6, and granulocyte colony-stimulating factor (G-CSF) showed transduction efficiencies ranging from 5-45%, as measured by acquisition of G418 resistance . The average efficiencies of gene transfer from multiple experiments for PB, BM, and CB were not statistically different . To determine the effect of ex vivo expansion on gene transfer into CB CD34+ cells, we compared the transduction efficiencies of cells exposed to virus immediately after harvest and CD34 selection or after 6 days of culture CD34+ CB cells were more effectively transduced after expansion in culture, showing gene transfer efficiencies 3- to 5-fold higher on day 6 compared with day 0 . Last, we examined retroviral transduction via spinoculation of CB CD34+ cells and found it to be approximately as effective as our standard transduction with no significant loss of cell viability as measured by colony formation in semi-solid medium. Brain Res Mol Brain Res, 1997 Dec 1, 52(1), 166 - 9 Inhibitory activity of a naturally occurring heterocyclic beta-substituted alanine, beta-(isoxazolin-5-on-4-yl)-L-alanine, on the L-glutamate/L-aspartate transporter (GLAST) expressed in Xenopus oocytes; Kusama-Eguchi K et al.; Excitatory amino acid (EAA) transporters are of physiological importance in the regulation of the extracellular concentration of excitatory amino acids and the neuroexcitation in CNS . Among four identified transporters, the Na+-dependent high-affinity L-glutamate/L-aspartate transporter (GLAST) is highly expressed in glial cells . Here, we report a naturally occurring inhibitor of GLAST, derived from bovine retina, using the Xenopus oocyte expression system . Beta-(isoxazolin-5-on-4-yl)-L-alanine (TAN), an antifungal antibiotic, inhibited {14C}L-glutamate (L-Glu) transport into GLAST-expressing oocytes . TAN also served as a substrate for this transporter in voltage-clamp experiments measuring the current coupled to the EAA transport . The maximum current of TAN itself was approximately 1/3 of that of L-glutamate, and its apparent affinity was almost the same as L-Glu . In combination with L-Glu, TAN antagonized L-glutamate transport . In radioisotope experiments, the inhibitory potency of this compound against {14C}L-Glu uptake into oocytes was approximately 1/6 of that of L-(-)-threo-3-hydroxyaspartate (THA) . The glucoside of TAN (TANG), occurring in seedlings of the garden pea, the lentil and some Lathyrus species, did not show any electrophysiological activity nor was it transported into oocytes . It is proposed that TAN is a novel type antagonist of natural origin on GLAST . By affecting such transport system, naturally occurring compounds may affect the regulation of the extracellular level of endogenous EAA. Antimicrob Agents Chemother, 1998 Jan, 42(1), 78 - 82 Postantibiotic effect in Escherichia coli determined with real-time metabolic monitoring; Libby JM; Metabolic activity was used to quantify the delay in recovery of Escherichia coli after limited exposures to cefotaxime and piperacillin . This was measured with a microphysiometer, a device which measures changes in pH in the cellular environment, which in turn reflects the metabolic activity of the cells . The antibiotics were rapidly pumped into and flushed from each cellular environment . The length of time that the bacteria were exposed to either antibiotic was determined by programmed valve changes . Metabolic activity was measured during periods in which the instrument's pumps were off . Graphical analysis of the data was used to determine the postantibiotic effect . The lengths of the postantibiotic effects of both drugs (95 to 101 min) determined with the microphysiometer corresponded with the reappearance of short, highly motile cells in significant numbers. Antimicrob Agents Chemother, 1998 Jan, 42(1), 18 - 22 Atomic force microscopy: application to investigation of Escherichia coli morphology before and after exposure to cefodizime; Braga PC et al.; Atomic force microscopy (AFM) is a recently developed technique that allows for the investigation of the surface morphology of a biological specimen at an unprecedented level of resolution . The aim of the present study was to explore some of the new opportunities offered by AFM by studying the morphological and surface alterations induced in Escherichia coli by supra-MICs and sub-MICs of a beta-lactam antibiotic (cefodizime) . The underlying principle of AFM is the scanning and sensing of the topography of a sample by means of near-field microscopy that makes it possible to obtain simultaneous digital measurements of the x, y, and z coordinates of any point on the bacterial surface with great resolution (x and y, approximately 20 A; z, approximately 1 A) . Unlike scanning electron microscopy, performance of AFM does not require a vacuum, drying to the critical point, or the coating of the bacterial surface with a metal layer . The digital storage of the information makes it easy to rotate the image, observe the bacterial surface and induced structural alterations from different points of view, and obtain a cross-section at any desired point with precise, automatic measurement of the heights and sizes of normal versus damaged bacteria . Use of the new and outstanding technique of AFM will make it possible for researchers to investigate biological samples immersed in biological fluids and will also make it possible for them to study the morphological alterations of living bacteria exposed to antibiotics as they are taking place. J Steroid Biochem Mol Biol, 1997 Sep-Oct, 63(1-3), 29 - 36 Autocrine and paracrine actions of breast tumor aromatase . A three-dimensional cell culture study involving aromatase transfected MCF-7 and T-47D cells; Sun XZ et al.; Stable aromatase-expressing MCF-7 and T-47D cell lines (i.e . MCF-7aro and T-47Daro) have been prepared by aromatase cDNA transfection and G418 (neomycin) selection . MCF-7aro was further subjected to a clonal purification . Aromatase activity in the transfected MCF-7 and T-47D cell lines was determined to be 73 +/- 6 pmol/mg/h and 48 +/- 4 pmol/mg/h, respectively . It is thought that these cell lines express aromatase in a stable manner, as demonstrated by a steady expression of the enzyme during culture in the absence of G418 . The growth of these cells could be stimulated by androgens (1-10 nM) as demonstrated through a spheroid culture method . The androgen-stimulated growth could be suppressed by 4-hydroxyandrostenedione (4-OHA) (0.01-0.1 mM) or tamoxifen (50 nM-1 microM) . In order to test the hypothesis that tumor aromatase can affect breast tumor growth in a paracrine manner, we have carried out cell culture experiments by co-culturing MCF-7 cells with either MCF-7aro or T-47Daro cells . Testosterone (1 nM) increased cell growth to a similar degree for MCF-7/MCF-7aro co-culture (0.75 x 10(6) cells each type) as with MCF-7aro only (2- to 3-fold) . In addition, the enzyme activities remained unchanged for MCF-7/MCF-7aro co-culture samples with and without androgen treatment, indicating that estrogen produced by transfected cells can also stimulate the growth of untransfected cells . The androgen response could be inhibited by an addition of 4-OHA (0.01-0.1 mM) . For MCF-7/T-47Daro co-culture experiments, a clear induction of cell growth by androgen was observed, and the level of the increase was similar to that on T-47Daro only . However, for either culture with T-47D only or with MCF-7/T-47Daro co-culture, the aromatase activity was found to increase significantly after testosterone treatment . T-47Daro cells were not subjected to a clonal purification, and it is therefore thought that the androgen treatment may selectively stimulate the growth of high aromatase-expressing T-47Daro cells . These results indicate that estrogen synthesized by tumor aromatase can stimulate breast tumor growth in both an autocrine and a paracrine manner. Crit Care Clin, 1998 Jan, 14(1), 55 - 70 Infection control concepts in critical care; Dieckhaus KD et al.; Patients with critical illnesses requiring aggressive medical intervention are at risk of acquiring serious nosocomial infection that may lead to increases in medical expenditures, morbidity, and mortality . Infection control in this population entails continuous surveillance for hospital-acquired infection, with investigation of outbreaks . Policies for effective antibiotic utilization, disinfection of medical devices and hospital environment, and patient isolation may limit nosocomial infection in this population . Finally, an effective infection control program should protect the health care worker from hospital-acquired infections through educational programs, routine health surveillance, vaccinations, and post-exposure care. Aust N Z J Med, 1997 Aug, 27(4), 403 - 7 Low-risk febrile neutropenia in a medical oncology unit; Leong DC et al.; BACKGROUND: Febrile neutropenia occurring in patients receiving chemotherapy for solid tumours or lymphoma is usually of short duration, and therefore may have a better outcome compared to patients with acute leukaemia or patients receiving myeloablative chemotherapy . AIMS: To review retrospectively the outcomes for febrile neutropenia occurring in patients of the Medical Oncology Unit at our institution, and to identify factors associated with worse outcome, particularly prolonged admission or death . METHODS: We reviewed 102 episodes of febrile neutropenia occurring in 85 patients treated between 1992 and 1994 . Demographic factors, tumour-related factors and clinical aspects of the episodes were correlated with outcome . RESULTS: The median age was 60 years (range, 18-87), with 56 (55%) episodes occurring in females . Twenty-eight (27%) episodes occurred in patients with lymphoma, with the remaining 74 (73%) occurring in patients with solid tumours . At presentation, the median absolute neutrophil count (ANC) was 0.14 x 10(9)/L with a median duration of significant neutropenia (ANC < 0.5 x 10(9)/L) of three days . The median duration of fever was two days . Twenty-nine (28%) episodes had positive cultures; of these 11 had bacteraemia . Forty-four (43%) episodes were classified as unexplained fevers . The remaining 29 episodes were associated with clinically documented infection but negative cultures . There was a high treatment success rate (81%) with first-line empirical antibiotics . Of 19 treatment failures, 13 were due to the necessity for antibiotic modification; the other six patients died from infection . Factors associated with a worse outcome (including prolonged admission and death) include: diagnosis of lymphoma; increasing number of chemotherapy courses; early onset of neutropenia; pneumonia; severe hypotension; and multiple co-morbidities . CONCLUSIONS: Febrile neutropenia in adult patients with solid tumours or lymphoma is associated with a relatively good outcome, possibly due to the short duration of neutropenia . A future prospective study to validate the risk factors identified in this study would be useful for defining patients at low risk for the adverse outcomes examined, in whom less intensive management for this condition may be possible. Arch Intern Med, 1998 Jan 26, 158(2), 151 - 6 Is routine replacement of peripheral intravenous catheters necessary? Bregenzer T, Conen D, Sakmann P, Widmer AF. BACKGROUND: Guidelines developed by the Centers for Disease Control and Prevention, Atlanta, Ga, recommend that peripheral intravenous catheters be changed every 3 days . However, routine replacement of central venous catheters is no longer supported in their latest update . OBJECTIVE: To evaluate the risk to patients of having peripheral intravenous catheters left in place for as long as they are clinically indicated . METHODS: This observational study in a university-affiliated, 700-bed hospital was designed to evaluate the day-specific risk (incidence density) for phlebitis, catheter infection, and obstruction with catheters remaining in place as long as clinically indicated . All consecutive patients who required peripheral intravenous catheterization for 24 hours or more were enrolled during a 10-