Antibiotics

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-week period . Outcome variables are phlebitis, catheter-related infections, and obstruction . Evaluated risk factors include age, sex, underlying disease, anatomical insertion site, catheter diameter, first or subsequent catheter, duration of catheterization, type of admission, hospital location, type of infusate, and antibiotic therapy . RESULTS: A total of 609 catheters that were in place for 1 to 28 days were evaluated . Phlebitis, catheter-related infection, and obstruction occurred in 19.7%, 6.9%, and 6.0% of catheters, respectively . We were unable to demonstrate an increased risk after 3 days of catheterization . The day-specific risk indicated a linear function of all outcome variables . CONCLUSIONS: The hazard for catheter-related complications--phlebitis, catheter-related infections, and mechanical complications--did not increase during prolonged catheterization . The recommendation for routine replacement of peripheral intravenous catheters should be reevaluated considering the additional cost and discomfort to the patient.

Am J Gastroenterol, 1998 Jan, 93(1), 5 - 10
Adding once-daily omeprazole 20 mg to metronidazole/amoxicillin treatment for Helicobacter pylori gastritis: a randomized, double-blind trial showing the importance of metronidazole resistance; Veldhuyzen van Zanten S et al.; OBJECTIVE: We compared the Helicobacter pylori eradication rate after a 14-day treatment with amoxicillin 500 mg t.i.d . and metronidazole 500 mg t.i.d . with or without omeprazole 20 mg once daily . METHODS: This was a randomized, controlled trial in which omeprazole was given in double-blind fashion . Patients with H . pylori-associated gastritis were enrolled in four centers in Canada from July 1991 to January 1994 . Eradication of H . pylori was assessed by histological evaluation and culture of endoscopic biopsies obtained from the antrum and corpus of the stomach . RESULTS: The H . pylori eradication rate was 73% (33 of 45) in the omeprazole-amoxicillin-metronidazole group, compared with 66% (31 of 47) in the amoxicillin-metronidazole group . This 7% difference was not statistically significant (p = 0.43, 95% confidence interval for difference -11% to 26%) . Metronidazole primary resistance in the prestudy cultures was found more frequently in the omeprazole-amoxicillin-metronidazole group than in the amoxicillin-metronidazole group . Resistance to metronidazole was an important predictor of treatment failure . The H . pylori eradication rate was 61% (19 of 31) for patients infected with metronidazole-resistant H . pylori strains, compared with 91% (30 of 33) eradication for those infected with metronidazole-sensitive strains (p < 0.01) . Vaginal candidiasis was reported in four patients . CONCLUSIONS: The H . pylori eradication rate was higher (73%) for omeprazole-amoxicillin-metronidazole than for the dual antibiotic therapy given without omeprazole (66%); however, this difference was not statistically significant . Metronidazole resistance significantly reduces H . pylori eradication rates.

J Laparoendosc Adv Surg Tech A, 1997 Aug, 7(4), 205 - 11
Mini-laparoscopic cholecystectomy: a cosmetically better, almost scarless procedure; Yuan RH et al.; Laparoscopic cholecystectomy is the most common laparoscopic operation in the world and is accepted as the standard procedure for cholecystectomy . Although use of miniendoscope in diagnosis of gynecological disease has been performed for decades, using a 2-mm mini-laparoscope for cholecystectomy is new . From November 1996 to January 1997, 14 patients (6 men, 8 women; mean age 47 years) with gallbladder stone disease were treated by mini-laparoscopic cholecystectomy at National Taiwan University Hospital, Taipei, Taiwan . The entire procedure was done through four ports (an 11-mm subumbilical working port, a 2-mm subxiphoid video port, one 2-mm mid-clavicular retraction port, and one anterior axillary retraction port) . The operative time for these patients ranged from 30 to 150 min, with an average time of 79.29 min . Suturing was not necessary for the three 2-mm wounds . The estimated blood loss was minimal, and no intraoperative transfusions were required . All patients were able to tolerate feeding within 8 h . The average postoperative hospital stay was 1.57 days . Neither complications nor operation-related mortality were seen . In conclusion, mini-laparoscopic cholecystectomy is a feasible and safe procedure with nearly scarless wounds with a much better cosmetic effect, especially for young female patients.

J Pharm Biomed Anal, 1997 Sep, 16(1), 131 - 7
Development and validation of a method to extract and quantitate paromomycin and gentamicin from an Aquaphilic cream formulation; Pick J et al.; Butanol and dilute sulfuric acid were used to extract paromomycin and gentamicin from Aquaphilic-based formulated creams . The extraction procedure was validated over different antibiotic concentration ranges for linearity, precision, accuracy, limited specificity, sensitivity and solution stability.

Neth J Med, 1997 Oct, 51(4), 123 - 8
Spontaneous bacterial peritonitis . Detection, treatment and prophylaxis in patients with liver cirrhosis; Jansen PL; Spontaneous bacterial peritonitis (SBP) is a common complication in patients with liver cirrhosis and ascites . When a patient with liver cirrhosis and ascites presents with fever and/or abdominal pain, or a tender abdomen on physical examination, or with refractory ascites, an ascitic fluid aspirate should be obtained for culture and leucocyte count . The diagnosis of SBP is mainly based on the number of leucocytes or neutrophils in the ascitic fluid . Third-generation cephalosporins are the drugs of choice in the treatment of this disease . Since the recurrence rate is high, and in patients with decompensated liver cirrhosis associated with a definite mortality, prophylactic antibiotic therapy is indicated after a first episode of SBP.

Orthopade, 1997 Oct, 26(10), 902 - 7
{Garré sclerosing osteomyelitis}; Vienne P et al.; Osteomyelitis sclerosans Garre is still not completely understood . In spite of the fact that it is caused by bacterial infection, in most cases no bacterial growth can be discovered in culture . Furthermore, it remains open whether the chronic process is maintained by low-grade persistent infection or is maintained by itself after sterilization of the infection . Newer studies that may prove the presence of bacteria, e.g., by PCR, may elucidate the causes in the future . Sclerosing bone disease, sometimes multifocal, which present the same clinical, radiographic and histological features as chronic sclerosing osteomyelitis may be associated with diseases such as palmoplantar pustulosis, colitis ulcerosa, Crohn's disease, etc . and are reported as SAPHO (synovitis acne pustulosis hyperostosis osteitis) syndrome . In these diseases bacterial growth is almost always negative . However, temporary improvement under antibiotic therapy may be observed . A relationship between typical isolated chronic sclerosing osteomyelitis and SAPHO syndrome may exist, but the diseases should at present be differentiated . Neoplasms such as osteoid osteoma, Ewing sarcoma, or eosinophilic granuloma may simulate primary sclerosing osteomyelitis, and pathological examination of peripherally taken specimens may appear to be compatible with the diagnosis of sclerosing osteomyelitis . It should be appreciated that malignant tumors--even though this is the exception--can present a chronic, mild picture . Treatment of osteomyelitis sclerosans Garre needs be determined on an individual basis . A conservative approach with antibiotics usually leads only to temporary pain relief . The biopsy with opening of the medullary canal is sometimes sufficient for healing, while in extreme situations only segmental or even complete resection of the diseased bone case result in a permanent cure.

Orthopade, 1997 Oct, 26(10), 820 - 9
{Osteomyelitis during the growth period . Diagnostic imaging}; Zieger B et al.; In acute osteomyelitis of childhood a rapid diagnosis and initiation of antibiotic therapy is necessary in order to prevent late sequelae . Thus, diagnostic imaging plays a crucial role . If acute osteomyelitis is suspected in a child, imaging starts with conventional radiography in order to exclude other differential diagnoses . This is followed by sonography for the purpose of diagnosing a subperiosteal abscess or joint fluid from which the causative organism could be isolated . If the diagnosis is unclear, the next step should be either MRI or 99mTc-MDP bone scan, depending on the possibility of clinical localization and the site of the suspected lesion . MRI is superior to bone scan in depicting the exact anatomy, which is extremely important in spinal osteomyelitis and preoperatively . The bone scan can show the whole skeleton in one examination and should be favored if there is no definite localization or in suspected multifocal osteomyelitis . Rarely scintigraphy with labeled white blood cells is indicated . The 67Ga scan, however, should not be used in children because of the high level of radiation exposure . The different imaging modalities are described in detail and an imaging diagnostic workup is outlined.

Chirurgia (Bucur), 1997 Jul-Aug, 92(4), 221 - 5
{Plastic repair with Plastex-type synthetic mesh in abdominal wall defects}; Mogos D et al.; This paper analyses a statistical series of 53 patients suffering from single or multiple abdominal wall defects and who were managed by plastic surgery with Plastex type synthetic mesh . Our results are pleading for the extension of the indications of Plastex mesh buttressing surgery beyond the usual recurrent "hernia" cases to the patients admitted with nonrecurrent either large abdominal wall defects or, and poor-quality musculoaponevrotic parietes of the abdominal wall . Our study recorded recurrence and postoperative morbidity rates have been minimal due to both a correct selection of cases for this type of surgical repair and an adequate patient preoperative management in which antibiotic and thromboembolic prophylaxis have been applied on a regular basis.

Laryngoscope, 1998 Jan, 108(1 Pt 1), 97 - 101
Tube placement: a prospective, randomized double-blind study; Derkay CS et al.; Bilateral myringotomy with tympanostomy tube placement is the second most frequently performed pediatric surgical procedure, next to circumcision . Postoperative pain relief for children undergoing this procedure has been an ongoing concern . The authors undertook a prospective, randomized, double-blind, placebo-controlled clinical study in 200 consecutive children to investigate the efficacy of oral acetaminophen, acetaminophen with codeine, ibuprofen, and placebo administered preoperatively in relieving postoperative pain in children undergoing this procedure . All children received topical analgesia consisting of antibiotic eardrops mixed with 4% lidocaine intraoperatively . There was no significant difference in postoperative pain score between the four groups (P > 0.4447) . Thus it is likely that the intraoperative administration of antibiotic eardrops mixed with 4% lidocaine is all that is required to alleviate postoperative pain in children undergoing myringotomy with tympanostomy tube placement . Preoperative oral analgesics are apparently of little added benefit.

Chem Biol, 1997 Nov, 4(11), 833 - 43
RNA aptamers to the peptidyl transferase inhibitor chloramphenicol; Burke DH et al.; BACKGROUND: The problem of how macromolecules adopt specific shapes to recognize small molecules in their environment is readily addressed through in vitro selections (the SELEX protocol) . RNA-antibiotic interactions are particularly attractive systems for study because they provide an opportunity to expand our understanding of molecular recognition by RNA and to facilitate ribosomal modeling . Specifically, the antibiotic chloramphenicol (Cam) naturally binds bacterial ribosomes in the 'peptidyl transferase loop' of 23S ribosomal RNA to inhibit peptide bond formation . RESULTS: We identified Cam-binding RNA molecules ('aptamers') from two independent initial random RNA populations . Boundary determinations, ribonuclease S1 sensitivity analyses and the activity of truncated minimal RNAs identified a structural motif that is shared by sequences from both selections . The pseudosymmetric motif consists of a highly conserved central helix of five to six base pairs flanked by A-rich bulges and additional helices . Addition of Cam prior to ribonuclease S1 protected nucleotides in the conserved cores from cleavage . Reselection from a pool of mutated variants of the minimal aptamer further refined the sequence requirements for binding . Finally, we used proton nuclear magnetic resonance (NMR) to establish a 1:1 RNA: Cam stoichiometry of the complex . Both the protection and NMR data both show that Cam stabilizes the active fold of this aptamer . CONCLUSIONS: There are many different RNA sequences that can bind Cam . The Cam aptamers that we examined have a well-defined secondary structure with a binding pocket that appears to be stabilized by Cam . This RNA motif superficially resembles the Cam-binding site in 23S rRNA, although further work is needed to establish the significance of these similarities.

Pharmacol Toxicol, 1997 Dec, 81(6), 271 - 5
Neuroprotective effect of dapsone against quinolinate- and kainate-induced striatal neurotoxicities in rats; Santamaria A et al.; We tested the ability of dapsone, a well-known antibiotic and antiinflammatory drug, to attenuate both the quinolinic acid (an NMDA agonist of glutamate receptors)- and kainic acid (a non-NMDA agonist of glutamate receptors)-induced in vivo neurotoxicities in rats . Circling behaviour and striatal gamma-aminobutyric acid (GABA) depletion were considered as behavioural and neurochemical end-points of brain toxicity . Rotation behaviour, evaluated six days after the intrastriatal injection of quinolinic acid (130 +/- 19 ipsilateral turns/hr), was attenuated by doses of 12.5 mg/kg and 25 mg/kg of dapsone (50 +/- 9 and 63 +/- 9 turns/hr, respectively) . Striatal GABA levels (237.3 +/- 15.1 micrograms/g in control rats), found depleted at day 7 after quinolinic acid (98.3 +/- 8.6 micrograms/g), were also protected by dapsone at doses of 12.5 and 25 mg/kg (167.7 +/- 19.5 and 236.4 +/- 46.6 micrograms/g, respectively) . No protective effects were observed on quinolinic acid-induced neurotoxicity, as evaluated by both parameters, at lower doses of dapsone (6.25 and 9.375 mg/kg) . The action of dapsone, at the dose of 12.5 mg/kg, was also measured on kainic acid-induced depletion of the striatal GABA levels . Animals treated with dapsone + kainic acid (182.8 +/- 27.1 micrograms/g) showed significant attenuation of GABA depletion, as compared to rats treated with kainic acid alone (122.2 +/- 19.9 micrograms/g) . These findings provide evidences to suggest that dapsone is acting as a neuroprotective agent against excitotoxicity induced by glutamate receptor agonists.

Mol Pharmacol, 1998 Jan, 53(1), 77 - 87
Recognition of specific sequences in DNA by a topoisomerase I inhibitor derived from the antitumor drug rebeccamycin; Bailly C et al.; We investigated the interaction with DNA of two synthetic derivatives of the antitumor antibiotic rebeccamycin: R-3, which is a potent topoisomerase I inhibitor and contains a methoxyglucose moiety appended to the indolocarbazole chromophore, and its aglycone, R-4 . Spectroscopic measurements indicate that R-3 intercalates into DNA and that its carbohydrate domain contributes significantly to reinforce the affinity for DNA . Two complementary ligation assays concur that R-3, but not its aglycone counterpart, exerts a significant effect on the curvature and/or the flexibility of DNA . The sugar moiety may be responsible for preferential binding of R-3 to circular (or bent) DNA molecules as opposed to linear DNA fragments . The sequence selectivity of binding to DNA has been studied thoroughly by footprinting with DNase I and two other nucleases . The glycosylated compound is highly selective for nucleotide sequences containing GpT (ApC) and TpG (CpA) steps . The derivative lacking the sugar moiety on the indolocarbazole chromophore binds at essentially identical sites but with considerably lower affinity, so it seems that the chromophore rather than the carbohydrate is responsible for the preferential binding to sequences surrounding GpT and TpG steps . The influence of the exocyclic substituents present on the bases at the recognition sites (i.e., the 2-amino group of guanine and the 5-methyl group of thymine) was evaluated using two series of modified DNA molecules prepared by polymerase chain reaction containing inosine and/or 2,6-diaminopurine and uridine and/or 5-methylcytosine residues . The introduction of the amino group onto purine residues or the addition of a methyl group to pyrimidine residues suffices to create new drug binding sites . Therefore, unlike most DNA-binding small molecules, the rebeccamycin analogue seems to be highly sensitive to any modification of the exocyclic substituents on the bases in both the major and minor grooves of the double helix . The footprinting profiles with the different DNA fragments bear a remarkable resemblance to those determined for nogalamycin and bisnaphthalimide compounds known to recognize their preferred GpT and TpG sites via intercalation from the major groove . The unique DNA binding characteristics of the rebeccamycin analogue correlate well with its inhibitory effects on topoisomerase I.

Lasers Surg Med, 1998, 22(1), 37 - 41
Generation of infectious retrovirus aerosol through medical laser irradiation; Ziegler BL et al.; A novel model system was used to investigate the spread of infectious particles and live cells through the application of lasers commonly used in clinical medicine . Supernatants from a cell line producing recombinant retroviruses carrying a marker gene (neoR) were exposed to Er:YAG-laser beams . Aerosols were collected from various sites and distances from the point of laser impact and were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for neoR . In addition, a susceptible indicator cell line was used to investigate the presence of infectious virions in collected aerosols . To test the possibility of dissemination of viable cells, a cell line was laser irradiated, and the generated aerosols were analyzed for the presence of viable cells . The viral marker gene neoR could be detected in 16% (distance: 5.0-6.3 cm) to 59% (0.5-1.6 cm) of wells adjacent to the point of laser impact . The presence of infectious viruses in laser vapors conferring G418 resistance could be detected in 3% (distance 5.0-6.3 cm) to 20% (distance: 0.5-1.6 cm) of wells containing susceptible cells, and subsequent PCR analysis of isolated resistant clones revealed the presence of neoR-RNA and -DNA . Viable cells were detected in 40% (distance 0.7-3.6 cm) to 3% (distance 10.7-11.8 cm) of wells adjacent to the point of laser impact . These results demonstrate that laser vapors can contain infectious viruses, viral genes, or viable cells and may promote the spread of infections or tumor cell dissemination.

J Bone Miner Res, 1998 Jan, 13(1), 20 - 30
Osteoprogenitor cells as targets for ex vivo gene transfer; Onyia JE et al.; We transduced osteoprogenitor cells with recombinant retrovirus and analyzed proviral integration patterns into chromosomal DNA to detect for the first time the clonal and cellular fate of osteoprogenitor-derived progeny cells . Metaphyseal bone cells and diaphyseal stromal cells were isolated from the distal femurs of young rats, transduced with the vM5neolacZ recombinant retrovirus, and selected in the neomycin analog, G418 . Following surgical marrow ablation of a femur in one leg of mature rats, retroviral-transduced metaphyseal or diaphyseal cells were injected into the ablated site . These rats were killed 5-6 days later . Metaphyseal and diaphyseal cells were isolated from distal femurs, selected in G418, and stained for beta-galactosidase (beta-gal+) . The number and clonal origin of transduced progenitor cells were determined . High numbers of beta-galactosidase colonies with an osteoblast phenotype were obtained following metaphyseal transplants and detected in 100% of metaphyseal and none of diaphyseal specimens . In contrast, beta-galactosidase colonies derived from diaphyseal transplants were detected in 50% of specimens in both the metaphysis and diaphysis, and the absolute number of progenitor cell colonies was 60-fold less than metaphyseal transplants . Provirus was only detected in the ablated bones and not in the contralateral bone or other tissues . Proviral integration fragment analysis showed a single integration site for recovered metaphyseal cell clones, consistent with their origination from a common single progenitor . This is one of the first demonstrations of successful transplantation of clonal osteoprogenitors to their site of origin in bone . It may be possible to use these cells to target genes to bone for therapeutic use in skeletal and hematopoietic diseases.

Infect Control Hosp Epidemiol, 1997 Dec, 18(12), 831 - 49
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 programs 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.

J Bacteriol, 1998 Jan, 180(2), 359 - 65
Identification of the rrmA gene encoding the 23S rRNA m1G745 methyltransferase in Escherichia coli and characterization of an m1G745-deficient mutant; Gustafsson C et al.; An Escherichia coli mutant lacking the modified nucleotide m1G in rRNA has previously been isolated (G . R . Bjork and L . A . Isaksson, J . Mol . Biol . 51:83-100, 1970) . In this study, we localize the position of the m1G to nucleotide 745 in 23S rRNA and characterize a mutant deficient in this modification . This mutant shows a 40% decreased growth rate in rich media, a drastic reduction in loosely coupled ribosomes, a 20% decreased polypeptide chain elongation rate, and increased resistance to the ribosome binding antibiotic viomycin . The rrmA gene encoding 23S rRNA m1G745 methyltransferase was mapped to bp 1904000 on the E . coli chromosome and identified to be identical to the previously sequenced gene yebH.

Res Exp Med (Berl), 1997, 197(4), 189 - 97
Clarithromycin is a potent inhibitor of tumor-induced angiogenesis; Yatsunami J et al.; We investigated the inhibitory effect of clarithromycin, a 14-membered ring macrolide antibiotic, on tumor-induced angiogenesis in vivo using a mouse dorsal air sac model . The inhibitory effect of clarithromycin was dose-dependent, and 100 mg/kg of clarithromycin administered intraperitoneally twice a day reduced the area of dense capillary network to about 30% that of the control . However, in concentrations up to 50 microM clarithromycin had no effect on lung cancer cells and human vascular endothelial cell growth, endothelial cell migration, or lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor . Clarithromycin in concentrations greater than 10 microM inhibited endothelial cell tube formation on Matrigel in a dose-dependent manner . These data suggest clarithromycin is a potent inhibitor of tumor-induced angiogenesis that exerts its effect by inhibiting endothelial cell tube formation, and may be a possible candidate for therapeutic application.

J Physiol Pharmacol, 1997 Sep, 48 Suppl 4, 93 - 105
Multicenter evaluation of dual-therapy (omeprazol and amoxycillin) for Helicobacter pylori-associated duodenal and gastric ulcer (two years of the observation); Gabryelewicz A et al.; Treatment with the proton pump inhibitor (omeprazole) and single antibiotic (amoxycillin), two synergistic compounds, can cure Helicobacter pylori (H . pylori) infection, but this therapy is not as effective as had been expected . However, some studies show promising results . The aim of our study was to evaluate the effect of two weeks dual-therapy with omeprazole (O) and amoxycillin (A) on gastric (GU) and duodenal ulcer (DU) patients: ulcer healing, eradication of the H . pylori and recurrence rate of the ulcer . We studied 216 patients (aged 18-70) endoscopically proven GU (58 patients) and DU (158 patients) . Rapid urease test from the two antrum biopses and two antral and two corporeal biopses using Giemsa stain method for confirmation of the H . pylori infection were used . The patients were treated with omeprazole 20 mg BID and amoxycillin 1.0 g BID for 2 weeks and investigated every 4 months during 2 years . Clearance effect of Hp infection was achieved in 65.1% GU and 66.4% DU patients . Eradication ("check point" after 4 months) in 43% DU and 56.6% GU patients was confirmed . Reinfection rate was found in 16% during 2 years . We conclude--dual-therapy (O and A) is not sufficiently effective to be recommended as an anti-H . pylori treatment . H . pylori eradication prevents recurrence of peptic ulcer and is an important issue in attempts to achieve permanent ulcer healing.

J Physiol Pharmacol, 1997 Sep, 48 Suppl 4, 39 - 46
Therapy of H . pylori infection; Bazzoli F et al.; A simple, safe and effective 1 week low dose triple therapy, omeprazole 20 mg u.i.d . clarithromycin 250 b.i.d . tinidazole 500 mg b.i.d . (OCT) was developed in response to the problems seen with standard triple and dual therapies . Standard triple therapy, bismuth and two antibiotics, in fact, is effective for the eradication of H . pylori but is of limited use, because of side effects and the patients low compliance . The combination of omeprazole plus one antibiotic, either amoxycillin or clarithromycin, has resulted in various rates of eradication in different geographical areas, most of them being inconsistent and low . The short term low dose triple therapy was therefore based on the rationale that measures aiming at reducing side effects and improving patient compliance with an appropriate combination of drugs would lead to a substantial improvement in the eradication rate . This regimen initially tested in H . pylori +ve patients with gastritis, is highly effective (> 90%) for long term eradication also in duodenal ulcer patients and in patients with gastric ulcer . Consistent results have been reproduced by several investigators with the same regime, whilst increasing dosages and duration of treatment does not seem to improve success rate . In alternative, omeprazole, clarithromycin, amoxicillin (OCA) has been also suggested to overcome the problem of metronidazole resistance, however recent studies seem to indicate that resistance to metronidazole does not seem to significantly influence outcome of OCT . In conclusion, also according to the recent Maastricht Consensus Report, the short term low dose triple therapy consisting of a PPI plus antibiotics--any two among clarithromycin, tinidazole/metronidazole and amoxycillin--currently represent the most effective approach to H . pylori eradication.

Toxicol Appl Pharmacol, 1997 Dec, 147(2), 204 - 13
Spermatogenic cell apoptosis induced by mitomycin C in the mouse testis; Nakagawa S et al.; Spermatogenic cell degeneration in the mature mammalian testis occurs both spontaneously during normal spermatogenesis and in response to cytotoxic agents . Mitomycin C (MC) is an antibiotic that affects DNA synthesis . In the present study, we examined the induction of mouse spermatogenic cell apoptosis by MC, using TdT-mediated dUTP-biotin nick end labeling (TUNEL) to detect high levels of DNA fragmentation in situ, transmission electron microscopy (TEM) to observe nuclear chromatin condensation, and molecular methods to detect DNA ladders . This study shows that in the testis of MC-treated mice: (i) apoptotic cell death with fragmentation of nuclear DNA is induced by MC dose-dependently, (ii) apoptotic cell death is most commonly found in the spermatogonia and less frequently in spermatocytes, and (iii) apoptotic cell death induced by MC is not specific for the seminiferous stage of the tubules . The present study suggests that the spermatogenic cell apoptosis induced by MC might be involved in its testicular toxicity.

Bull Hosp Jt Dis, 1997, 56(4), 251 - 4
The postoperative drain-clamping method for hemostasis in total knee arthroplasty . Reducing postoperative bleeding in total knee arthroplasty; Ryu J et al.; We attempted to decrease the amount of postoperative bleeding after total knee arthroplasty (TKA) by clamping the suction drain and through retrograde infusion of saline containing a low concentration of epinephrine . When TKA was completed and the sutured wound was bandaged, 50 ml of saline containing epinephrine diluted to 1:200,000 and 0.5 g of antibiotic was injected into the knee joint via the inserted suction drain . The drain was clamped for 20 hours and then unclamped to begin aspiration until 48 hours after surgery . To clarify the effectiveness of this method, patients were divided into three groups . Group I consisted of 116 knees (in 95 patients) infused with 50 ml saline containing a low dose of epinephrine: Group II was composed of 70 knees (42 patients) infused with 50 ml saline only; and Group III included 97 knees (78 patients) who did not undergo this drain-clamp method . The average amount of postoperative bleeding was 207 ml in Group I, 255 ml in Group II (p < 0.01), and 501 ml in Group III (p < 0.001) . With this method of using saline with a low dose of epinephrine and sustained clamping of up to 20 hours, we have been able to operate on elderly patients with rheumatoid arthritis without blood transfusion, even in cases of simultaneous bilateral TKA . Drain-clamping with saline infusion effectively controlled postoperative bleeding after TKA, and when epinephrine was added to the saline, the hemostatic effect was even greater than that of saline alone.

Am J Physiol, 1997 Dec, 273(6 Pt 1), L1208 - 19
Calcium-stimulated Cl- secretion in Calu-3 human airway cells requires CFTR; Moon S et al.; Human airway serous cells secrete antibiotic-rich fluid, but, in cystic fibrosis (CF), Cl(-)-dependent fluid secretion is impaired by defects in CF transmembrane conductance regulator (CFTR) Cl- channels . Typically, CF disrupts adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretion but spares Ca(2+)-mediated secretion . However, in CF airway glands, Ca(2+)-mediated secretion is also greatly reduced . To determine the basis of Ca(2+)-mediated Cl- secretion in serous cells, we used thapsigargin to elevate intracellular Ca2+ concentration ({Ca2+}i) in Calu-3 cells, an airway cell line bearing some similarities to serous cells . Cells were cultured using conventional and air interface methods . Short-circuit current (Isc) and transepithelial conductance (Gte) were measured in confluent cell layers . Thapsigargin stimulated large, sustained changes (delta) in Isc and Gte, whereas forskolin stimulated variable and smaller increases . delta Isc was decreased by basolateral bumetanide, quinidine, barium, or diphenylamine-2-carboxylate (DPAC) but was unaffected by high apical concentrations of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), 4,4'-dinitrostilbene-2,2'-disulfonic acid, and calixarene . Isc was measured after permeabilizing the basolateral membrane and establishing transmembrane ion gradients . Unstimulated apical membranes displayed high Cl- conductance (GCl) that was decreased by DPAC but not by DIDS . Apical GCl could be increased by elevating intracellular cAMP concentration but not {Ca2+}i . We conclude that CFTR channels are the exclusive GCl pathway in the apical membrane and display approximately 60% of maximum conductance at rest . Thus elevated {Ca2+}i increases K+ conductance to force Cl- through open CFTR channels . We hypothesize that loss of CFTR channels causes diminution of cholinergically mediated gland secretions in CF.

Rev Hosp Clin Fac Med Sao Paulo, 1997 Mar-Apr, 52(2), 111 - 7
{Outline of Lyme borreliosis in Brazil}; Yoshinari NH et al.; Since 1989, we have identified 25 patients with Lyme disease, 15 in early and 10 in latent stage, supporting its existence in Brazil, according to following reasons: 1) presence of clinical manifestations compatible with Lyme disease, with cutaneous, articular, nervous system and rarely cardiac envolvement; 2) presence of antibodies against Borrelia burgdorferi; 3) follow up of acute cases show sorologycal changes; 4) good antibiotic response at early stage of disease and only satisfactory in latent form; 5) mapping of risk areas, according to geographycal distribution of patients; 6) presence and identification of Ixodid ticks; 7) identification of micro-organism like borrelias in human, wild animals and ticks cultures, seen by dark field microscope; 8) sorology done in dogs and oxes, confirm existence of risk areas for Lyme disease.

Ann Hematol, 1997 Nov-Dec, 75(5-6), 243 - 6
Treatment with rhG-CSF for osteomyelitis in a patient with p47-phox-deficient chronic granulomatous disease; Isotani H et al.; A 24-year-old woman with osteomyelitis was diagnosed as having p47-phox-deficient chronic granulomatous disease (CGD) . The patient showed a marked deficiency of p47-phox, which is very rare in Japan . As the clinical response to various antibiotics including sulfamethoxazole-trimethoprim was not satisfactory, we added recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the treatment protocol . We report the beneficial clinical course of the patient, together with the effect of rhG-CSF on the granulocyte function, and the present report indicates that rhG-CSF is useful for the treatment of antibiotic-resistant infection in the variant type of p47-phox-defective CGD.

Mil Med, 1997 Dec, 162(12), 820 - 3
Five cases of Plasmodium falciparum malaria in active duty Navy personnel participating in Operation Assured Response; Orndorff G et al.; During Operation Assured Response in Liberia and Sierra Leone, between May and July 1996, five confirmed cases of falciparum malaria occurred in U.S . Navy personnel . The threat of malaria in west central Africa was recognized from the outset, and preventive medicine guidance was given to all the units participating in Operation Assured Response . The use of personal protective measures as well as drug chemoprophylaxis (daily doxycycline) was stressed . Among these cases, all patients admitted to either not using personal protective measures or not taking the medication as directed . This report serves to review the individual cases and remind the reader of the need to comply with prophylaxis, daily use of doxycycline, when prescribed.

Mil Med, 1997 Dec, 162(12), 808 - 11
War injuries to the extremities; Maricevic A et al.; AIM: The authors present their own experience in the treatment of war injuries to the extremities during the war in Croatia and in Bosnia and Herzegovina . METHOD: From November 1991 until April 1994, 186 patients with war injuries to the extremities were treated . Treatment began with first aid offered at the battlefield, followed by transport of patients to war hospitals, and transfer of the most severe cases to the rear hospital (Split University Hospital) . RESULTS: Isolated injuries to the extremities were present in 155 patients (83%), 38% of them with injuries to soft tissues of the extremities and 62% with both soft-tissue injuries and bone fractures . Associated minor injuries to the other parts of the body were present in 31 patients (17%) . Amputation of the extremity was performed on 22.5% of the patients . All fractures were treated by external fixation, whereas soft-tissue lesions were managed by debridement and excision of the damaged tissue, with compulsory antibiotic and antitetanic therapy . The rates of mortality and infection were 0.5 and 6.4%, respectively . CONCLUSION: Our experience emphasizes the importance of field hospitals in timely and adequate treatment of war wounds to the extremities . Treatment of the wound by a trained professional within 2 hours after wounding saved many lives and extremities . The patients were only rarely referred to the rear hospital.

Fetal Diagn Ther, 1997 Sep-Oct, 12(5), 274 - 8
Emergency cervical cerclage after 20 weeks' gestation: a retrospective study of 6 years' practice in 34 cases; Benifla JL et al.; The aim of this study was to evaluate the outcome of late emergency cervical cerclage, after 20 weeks' gestational age (GA) . This report describes a retrospective study from January 1, 1988 to December 31, 1993, of 34 patients with intact membranes who required emergency cervical cerclage after 20 weeks of GA, on observing significant cervical changes such as 'cervix dilated at least 2 cm and bulging membranes', in the Department of Obstetrics and Gynecology (Bichat-Claude Bernard Public Hospital, Paris, France) . Eight patients were primigestae, and 3 had twin pregnancies . After 48 h resting under tocolysis infusion, emergency cervical cerclage (MacDonald technique) was performed with general anesthesia and prophylactic antibiotic administration . Out of 34 patients, 19 (73.1%) had a past history of one or more previous obstetrical events capable of causing cervical incompetence (CI) . Mean duration of pregnancy at emergency cervical cerclage was 22.1 weeks of GA, and at delivery was 35.7 weeks of GA . The mean prolongation of pregnancy obtained was 13.9 weeks . There was a significant negative linear relationship between term at time of cerclage and the prolongation of pregnancy . In this series, 6 patients (17.6%) delivered before 28 weeks of GA, and 6 further patients (17.6%) delivered between 28 and 37 weeks of GA . Chorioamnionitis was observed in 5 cases (14.8%) . Overall the neonatal survival rate was 86.5%, with 5 deaths among a total of 37 newborn . Two fetuses died in utero as a consequence of chorioamnionitis, 2 twins died shortly after birth at 24 weeks of GA, and 1 died after failure of emergency cervical cerclage (peroperative rupture of membrane) . Out of 32 alive newborn, 7 were admitted to intensive care and were followed up at age 1 year with no signs of major handicap . On observing significant cervical changes with bulging membrane through an open cervix after 20 weeks of GA, an 'aggressive' multifactorial approach including cervical cerclage is legitimate and is associated with a satisfactory fetal survival rate with a minimum of maternal complications . However, in the absence of a controlled study and regardless of the major ethical problems this might entail, these beneficial effects described cannot be considered as proved.

Crit Care Med, 1998 Jan, 26(1), 88 - 91
Removal of piperacillin in critically ill patients undergoing continuous venovenous hemofiltration; Capellier G et al.; OBJECTIVE: Continuous hemofiltration is now widely used in the intensive care unit . Our study aimed to assess the removal of piperacillin under continuous hemofiltration and to define a suitable dosage regimen of administration . DESIGN: Prospective study of blood and ultrafiltrate concentrations of piperacillin to assess the pharmacokinetics of the antibiotic . SETTING: The medical intensive care unit of a teaching hospital . PATIENTS: Ten patients were included in the study . Six patients were receiving their first dose of piperacillin (group 1) and four had already been treated for 2 to 6 days (group 2) . The mean Simplified Acute Physiology II score was 74 +/- 6 (SEM), and the number of organ failures was 3.6 +/- 0.3 (range 3 to 5) . Renal failure was related to septic shock in seven patients and to cardiogenic shock in three patients . Seven patients were anuric . Hepatic dysfunction was present in four of the ten patients . INTERVENTIONS: Patients were treated with continuous venovenous hemofiltration using a hollow polysulfone capillary fiber . Piperacillin (4 g) was injected intravenously over 20 mins . Arterial blood and ultrafiltrate were sampled immediately before the injection and then every hour until 8 hrs after injection time . Piperacillin concentrations were assayed using high performance liquid chromatography . MEASUREMENTS AND MAIN RESULTS: In group 1, the mean serum peak concentration of piperacillin was in the normal range (125 +/- 21 mg/L), but trough values were higher (48 +/- 8 mg/L) than in normal subjects . In group 2, trough values before the injection were increased in all patients (188 +/- 71 mg/L) . At T1, blood peak concentration reached 470 +/- 127 mg/L . A small amount of piperacillin was retrieved from the ultrafiltrate . The elimination half-life was 5.1 +/- 1.4 and 4.8 +/- 1.4 hrs in groups 1 and 2, respectively . CONCLUSIONS: Piperacillin was not removed to a significant extent during continuous hemofiltration . Further, in the intensive care unit, patients in shock with multiple organ failure such as liver failure might behave differently from patients with stable end-stage renal disease . A 4-g dose of piperacillin twice a day is recommended in such patients.

Urol Int, 1997, 59(3), 177 - 81
Ureteroscopic treatment of ureteral stones: only an auxiliary measure of extracorporeal shockwave lithotripsy or a primary therapeutic option?
Osti AH, Hofmockel G, Frohmuller H.
Both extracorporeal shockwave lithotripsy (ESWL) and ureteroscopy are well-established methods in stone treatment; however, the therapeutic procedure in ureteral calculi, especially in the distal third of the ureter, is still controversially discussed . The aim of the present study was to examine the role of ureteroscopy as an auxiliary measure after ESWL and its importance as an alternative therapeutic option in the treatment of distal ureteral stones . Between 1991 and 1994, 115 ureteroscopic procedures in 104 patients with ureteral stones or stone fragments were carried out at our institution . During the same period of time, 1,595 patients with ureteral calculi (in the proximal two thirds of the ureter: n = 956; in the distal third of the ureter: n = 639) were treated with a Dornier HM-3 lithotriptor . In 77 of those 104 patients treated by ureteroscopy, this procedure was indicated as an auxiliary measure after failure of ESWL including 34 out of the 639 patients (5.3%) with stones in the distal part of the ureter . The overall direct success rate during the ureteroscopic stone treatment (including 11 cases with a second procedure) in the proximal, middle and distal third of the ureter was 74, 81 and 92%, respectively . The success rate of primary ureteroscopic removal of distal-third ureteral stones alone was 100% in 27 of these 104 patients . After 3 months the overall stone-free rate of all patients treated with ureteroscopy was 94% . Ureteroscopy appears to be a safe and effective treatment modality, if used as an auxiliary measure after failure of ESWL as well as a primary treatment modality in the case of stones in the distal third of the ureter . On the other hand, ESWL alone is a noninvasive and also successful procedure in treating stones situated in the distal part of the ureter.

Gene, 1997 Dec 12, 203(2), 175 - 81
Introns enable the polyomavirus middle and small T antigens to stimulate the growth of primary rat embryo fibroblasts; Asselin C et al.; We constructed spliceable vectors that separately encode polyomavirus MT and ST . The addition of an intron enables MT to transform and to immortalize more efficiently and ST to transiently stimulate the growth of primary rat embryo fibroblasts.

Gene, 1997 Dec 5, 203(1), 1 - 9
A second type-I PKS gene cluster isolated from Streptomyces hygroscopicus ATCC 29253, a rapamycin-producing strain; Ruan X et al.; Analysis of a 32.8-kb segment of DNA from the rapamycin (Rp) producer, Streptomyces hygroscopicus ATCC 29253, revealed a new type-I polyketide synthase (PKS) cluster consisting of four open reading frames (ORF 1-4), each encoding a single PKS module . The four ORFs are transcribed in the same direction and are flanked by several smaller ORFs (ORF 5-9), which may be related to the PKS cluster . The first PKS-containing ORF has a ligase domain at the N-terminus of the polypeptide . This domain has 55% aa identity to the CoA ligase domain of the Rp PKS (Schwecke et al., 1995 . Proc . Natl . Acad . Sci . 92, 7839-7843) which is also encoded in this strain (Lowden et al., 1996 . Angew . Chem . Int . Ed . Engl . 35, 2249-2251) . ORF5 (340 aa) and ORF6 (924 aa) were found to be homologous to RapK (41% aa identity) and RapH (35% aa identity), which are hypothesized to be a pteridine-dependent dioxygenase and a regulatory protein, respectively (Molnar et al., 1996 . Gene 169, 1-7) . In addition, ORF7 (391 aa) was found to have up to 42% aa identity to a number of plant 3-deoxy-D-arabino-heptulosonate-7-phosphate synthases (DAHPS) and 47% aa identity to PhzF, a bacterial DAHPS involved in phenazine antibiotic synthesis . The proximity of the DAHPS-encoding gene to the PKS cluster containing a Rp-like ligase domain suggests that a derivative of shikimate may be used as the PKS starter . ORF8 (283 aa) was found to have homology (32% aa identity) to a Synechocystis sp . gene of unknown function . The N-terminal portion of ORF9 was found to be similar to a tetracycline 6-hydroxylase (34% aa identity) from Streptomyces aureofaciens.

J Cataract Refract Surg, 1997 Nov, 23(9), 1324 - 30
Effect of topical anti-transforming growth factor-beta on corneal stromal haze after photorefractive keratectomy in rabbits; Thom SB et al.; PURPOSE: To determine the relationship between anti-transforming growth factor-beta (anti-TGF-beta) antibodies and the amount of corneal stromal haze after excimer laser photorefractive keratectomy (PRK) . SETTING: Wills Eye Hospital, Philadelphia, Pennsylvania, USA . METHODS: Nineteen rabbits had bilateral PRK . Dichlorotriazinyl fluorescein was used to stain the exposed stroma; all rabbits were then treated with antibiotic ointment for 4 days . Ten rabbits were randomized to treatment with topical anti-TGF-beta1, -beta2, and -beta3 antibody 50 microg three times a day for 4 days; the others received diluent three times a day for 4 days . Stromal haze was graded weekly for 8 weeks on a 0 to 4+ scale . At the end of the study, all corneas were examined histopathologically . RESULTS: All treated eyes developed appreciable haze . Seven control rabbits and one antibody-treated rabbit had an epithelial erosion (P = .00001) . Antibody-treated rabbits had significantly less haze at 3, 4, and 5 weeks (right eyes) and 3, 4, 5, 7 and 8 weeks (left eyes) (P < .05) . Histopathology and fluorescence microscopy showed subepithelial collagen deposition consistent with clinical haze . CONCLUSIONS: Topical anti-TGF-beta antibody reduced stromal haze after PRK in the rabbit model and may be clinically beneficial in humans.

Rinsho Kyobu Geka, 1994 Feb, 14(1), 49 - 52
{Right-sided infective endocarditis with ventricular septal defect}; Sasahashi N et al.; Two patients underwent surgical treatment for right-sided infective endocarditis with ventricular septal defect . In both cases, blood cultures showed Peptostreptococcus, and the operation was performed at non-active phase after antibiotics therapy . The case 1 was a 7-year-old girl who was observed a vegetation on the chorda of the anterior paillary muscle by echocardiography . The defect was directly closed and the vegetation was excised . The case 2 was 22-year-old female who had been diagnosed of VSD in her infancy . A high fever continued and echocardiography revealed a vegetation attached to the septal tricuspid leaflet . Partial excision of the leaflet and autopericard patch plasty was performed, and the VSD was directly closed . Postoperatively intravenous antibiotic therapy was given for periods of 6 weeks, and clinical course were uneventful in both cases . Local excision of vegetation and leaflet repair by autopericard patch plasty should be performed in cases with localized vegetation and minor valvular regurgitation.

Eur J Emerg Med, 1994 Jun, 1(2), 92 - 103
Bacterial meningitis: diagnostic and therapeutic considerations; Knockaert DC; In this review the epidemiology of bacterial meningitis and the new insights in the pathophysiology are thoroughly discussed . The different diagnostic steps are described and the present day antibiotic strategy and adjunctive inflammation-modulating therapy are delineated.

Biotechniques, 1997 Dec, 23(6), 1094 - 7
Compact, synthetic, vaccinia virus early/late promoter for protein expression; Chakrabarti S et al.; Vaccinia virus, a member of the poxvirus family, is widely used as a mammalian cell expression vector . Vaccinia virus replicates in the cytoplasm and has its own transcriptional system, making it necessary to use viral promoters . Here, we describe the design, construction and use of a 40-bp synthetic, vaccinia virus promoter with largely overlapping early and late regulatory elements . Convenient plasmid transfer vectors are depicted for expression of one or two genes under control of strong early/late promoters and allowing for thymidine kinase (TK) or antibiotic selection of recombinant viruses.

J Antimicrob Chemother, 1997 Nov, 40(5), 721 - 4
Effect of microencapsulated ampicillin on cell-mediated immune responses in mice; Barsoum IS et al.; The effects of free ampicillin, microencapsulated ampicillin anhydrate (MEAA) and antibiotic-free microspheres on the cell-mediated immune response in Balb/c mice were measured by lymphoproliferation assay, delayed-type hypersensitivity (DTH) and cytokine production . Injection into mice for seven consecutive days with equivalent subcutaneous doses of ampicillin, MEAA or placebo microspheres did not produce any consistent change in lymphocyte proliferation nor did it affect DTH responses or interleukin-2 production . Although the production of interleukin-4 in mice treated with ampicillin or MEAA increased compared with the control mice, this increase was not statistically significant . These results indicate that ampicillin and MEAA have similar effects on cell-mediated immunity in mice.

Brain Res Bull, 1997, 44(6), 707 - 13
Effect of sulfamethazine on sexual precocity and neuropeptide Y neurons within the tuberoinfundibular region of the chick brain; Walsh KM et al.; Neuropeptide Y (NPY) has been implicated in the sexual maturation process in chicks and other species . This study attempted to identify specific neural sites where NPY could influence gonadotrophin-releasing hormone (GnRH) neurons during maturation as evidenced by immunocytological changes . To do this sulfamethazine (SMZ), an antibiotic known to advance sexual maturation in male chicks, was used to elicit early testes development . One week posthatch, 20 chicks were fed either a control ration or one with 0.2% SMZ for 2 weeks or 5 weeks . At 3 and 6 weeks of age, birds were perfused through the heart, brains removed, and prepared for immunocytochemical assay for either NPY or GnRH . Results showed that chicks given SMZ had significantly greater testes weight compared to controls at both ages (p < or = 0.05) while body weight did not differ significantly between these groups at either age . The results of cell quantification showed no difference in the number of GnRH neurons between the SMZ chicks and controls in either the bed nucleus of the pallial commissure or the anterior lateral thalamic nucleus (LA) at 3 or 6 weeks of age . There was a significantly greater number of GnRH neurons found within the LA of 6-week compared to 3-week-old control chicks . A ratio of the mean width of the external zone (EZ) of median eminence (ME) to the total width of ME showed no significant difference between the experimental and control animals at either 3 or 6 weeks of age . The ratio EZ/ME did, however, increase as a function of age . The results of the assay for immunoreactivity to NPY showed no significant difference in the number of NPY neurons found within the nucleus marginalis tractus opticus between treatment groups at either age . A highly significant increase in NPY neurons was found within the infundibular nucleus (IN) and the internal zone of the ME of SMZ-treated chicks compared to controls at 3 weeks of age . Data suggest that NPY-like neurons within the IN complex may serve an important role regarding the early stages of sexual maturation in chicks.

Helicobacter, 1997 Dec, 2(4), 199 - 204
One week triple therapy for Helicobacter pylori: does high-dose clarithromycin confer additional benefit?
O'Connor HJ, Loane J, Bindel H, Bhutta AS, Cunnane K.
BACKGROUND . Clarithromycin, a new acid stable macrolide antibiotic with proven efficacy against Helicobacter pylori, has been widely incorporated into eradication regimens but its optimal dosage schedule remains controversial . The standard dose of clarithromycin is 250 mg twice daily . METHODS . In a prospective study designed to evaluate the helicobactericidal efficacy, patient acceptability, and ulcer healing efficacy of a triple therapy regimen incorporating high dose clarithromycin, 100 consecutive patients with H . pylori-positive peptic ulcer received omeprazole 20 mg twice daily in combination with metronidazole 400 mg twice daily and clarithromycin 500 mg twice daily for seven days . H . pylori status was assessed before and at least 4 weeks after therapy by rapid urease test and histology . Adverse events and compliance were assessed by direct questioning . RESULTS . Only two patients failed to attend for repeat endoscopy, leaving 98 evaluable patients . Of these, 94 were H . pylori-negative after therapy, giving an intention-to-treat eradication rate of 94% (95% confidence interval, 89%-99%) . The ulcer healing rate was 92% (86%-98%), and ulcer healing was significantly associated with H . pylori eradication (p < 0.01) . Adverse events were reported by 33% of patients of which nausea was the commonest (14%) . Noncompliance with therapy was significantly associated with H . pylori treatment failure (p < 0.001) . CONCLUSIONS . Seven day triple therapy incorporating high dose clarithromycin effectively eradicates H . pylori and heals ulcers, but it is disadvantaged by a relatively high rate of adverse events . In view of these findings and the fact that no direct comparison to date has shown increased efficacy from high dose clarithromycin, we would recommend continued use of low dose clarithromycin when combined with omeprazole and a nitroimidazole.

Helicobacter, 1997 Dec, 2(4), 159 - 71
Clarithromycin dual therapy regimens for eradication of Helicobacter pylori: a review; Pipkin GA et al.; BACKGROUND . Peptic ulcer disease can be cured by eradication of Helicobacter pylori during treatment to heal the ulcer . Dual therapy regimens were among the first to be granted approval for use . Reports of dual therapies including clarithromycin as the sole antibiotic are reviewed . METHODS . Reports were identified from literature up to May 1997 . Information reviewed included patient population, medical diagnosis, trial design, eradication regimens, and H . pylori eradication rates . The great diversity between studies limits formal meta-analysis but a measure of relative efficacy has been obtained by comparison of eradication rates derived by clearly defined methods and by pooling data . RESULTS . Seventy-five reports of trials with 104 dual therapy treatment arms were reviewed . H . pylori eradication rates reported with ranitidine bismuth citrate plus clarithromycin range from 70-96% with a pooled observed rate of 85% . With omeprazole plus clarithromycin, reported eradication rates range from 27-90% with the pooled reported rate being 66% . Few data are available with either lansoprazole or ranitidine hydrochloride plus clarithromycin . CONCLUSION . High H . pylori eradication rates derived by consistent and clearly defined methods have been seen with ranitidine bismuth citrate plus clarithromycin . Lower and more variable rates are reported with clarithromycin and either a proton pump inhibitor or a histamine H2-receptor antagonist.

Neurol Med Chir (Tokyo), 1996 Nov, 36(11), 808 - 11
Fatal subarachnoid hemorrhage from an inflammatory cavernous carotid artery aneurysm: failure of conservative treatment after early diagnosis--case report; Nawashiro H et al.; Inflammatory carotid artery aneurysm is a rare complication of acute paranasal sinusitis . A 50-year-old female presented with a ruptured giant carotid artery aneurysm secondary to infection of the sphenoid sinus and cavernous sinus . She had been healthy until 5 days before admission, when she developed orbital phlegmon and meningitis . She received antibiotic therapy for 10 days . Computed tomography (CT) of the brain 2 days after admission showed no abnormality . However, repeat CT on day 6 showed a round isodense mass in the suprasellar cistern suggesting a cerebral aneurysm . Twelve days after admission, she suffered a fatal subarachnoid hemorrhage . Cerebral angiography revealed a giant left cavernous carotid artery aneurysm with a very irregular shape . Autopsy found sphenoid sinusitis and osteomyelitis extending into the cavernous sinuses . Diagnosis of bacterial inflammatory aneurysms before rupture is very important . Appropriate surgical intervention should be considered if there is enlargement of the original aneurysm or appearance of a new aneurysm indicating a potentially dangerous situation.

Antimicrob Agents Chemother, 1997 Dec, 41(12), 2640 - 5
Pharmacokinetics of imipenem-cilastatin in critically ill patients undergoing continuous venovenous hemofiltration; Tegeder I et al.; The pharmacokinetics of imipenem-cilastatin were investigated in 12 critically ill patients with acute renal failure (ARF) managed by continuous veno-venous hemofiltration (CVVH) while receiving a fixed combination of 500 mg of imipenem-cilastatin intravenously three or four times daily . No adverse drug reactions were observed . Plasma and hemofiltrate samples were taken at specified times during one dosing interval, and the concentrations of imipenem and cilastatin were determined by high-performance liquid chromatography . Pharmacokinetic variables were calculated by a first-order, two-compartment pharmacokinetic model for both substances . Total clearances of imipenem and cilastatin (mean +/- standard deviations) were 122.2 +/- 28.6 and 29.2 +/- 13.7 ml/min, respectively, with hemofiltration clearances of 22.9 +/- 2.5 and 16.1 +/- 3.1 ml/min, respectively, and nonrenal, nonhemofiltration clearances of 90.8 +/- 26.3 and 13.2 +/- 13.9 ml/min, respectively . Mean imipenem dosage requirements were approximately 2,000 mg/24 h (2,111.8 +/- 493.4 mg/24 h) . They were calculated in order to achieve an average steady-state concentration of 12 mg/liter to ensure that concentrations in plasma exceeded the MICs at which 90% of intermediately resistent bacteria are inhibited (8 mg/liter) during the majority of the dosing interval . By contrast, the recommended dosage for patients with end-stage renal failure (ESRF) and infections caused by intermediately resistant bacteria is 1,000 mg/24 h . This remarkable difference may be due (i) to differences in the nonrenal clearance of imipenem between patients with ARF and ESRF and (ii) to the additional clearance by the hemofilter . Since the total clearance of cilastatin was low, marked accumulation occurred, and this was particularly pronounced in patients with additional liver dysfunction . Thus, in patients with ARF managed by CVVH, rather high imipenem doses are required, and these inevitably result in a marked accumulation of cilastatin . The doses of imipenem recommended for patients with ESRF, however, will lead to underdosing and inadequate antibiotic therapy.

J Infect Dis, 1998 Jan, 177(1), 224 - 7
Association of CD4 cell depletion and elevated blood and seminal plasma human immunodeficiency virus type 1 (HIV-1) RNA concentrations with genital ulcer disease in HIV-1-infected men in Malawi; Dyer JR et al.; CD4 cell counts and blood plasma and seminal plasma human immunodeficiency virus type 1 (HIV-1) concentrations were compared in HIV-1 RNA-seropositive men with urethritis and with or without genital ulcer disease (GUD) . GUD was associated with lower CD4 cell counts (median, 258 vs . 348/microL) and increased blood plasma HIV-1 RNA (median, 240 x 10{3} vs . 79.4 x 10{3} copies/mL) . Men with nongonococcal urethritis and GUD shed significantly greater quantities of HIV-1 in semen (median, 195 x 10{3} vs . 4.0 x 10{3} copies/mL) than men with nongonococcal urethritis without GUD . These levels decreased approximately 4-fold following antibiotic therapy . The results indicate an association between GUD and increased blood HIV-1 RNA levels . Increased HIV-1 in semen was demonstrated in some men with GUD; such an increase could lead to increased transmission, thus complicating interpretation of the role of the genital ulcer itself in the infectiousness of HIV . Reasons for increased HIV RNA in semen in men with GUD remain to be determined.

Clin Orthop, 1997 Dec, (345), 148 - 54
Bone loss associated with the use of spacer blocks in infected total knee arthroplasty; Calton TF et al.; Twenty-five knees in 24 patients with infected total knee replacements were treated with debridement, component removal, and insertion of an antibiotic impregnated cement spacer block . Intravenous antibiotics were administered for 6 weeks during which time the patients' knees were kept in a knee immobilizer nonweightbearing . These cases were reviewed retrospectively to determine radiographically the amount of bone loss that occurred during the period before reimplantation . Tibial and femoral bone loss occurred frequently from invagination of the cement spacer block into the femoral and tibial cancellous bone . Tibial bone loss was present in 10 (40%) cases and averaged 6.2 mm . Femoral bone loss was present in 11 (44%) cases and averaged 12.8 mm . Bone loss was more common when spacer blocks were undersized . None of the 15 spacer blocks that were made with a small intramedullary stem displaced . Three of the remaining 10 spacer blocks made without an intramedullary stem did displace with associated bone loss . Antibiotic spacer blocks used in the two-stage treatment of infected total knee replacements can be associated with subsequent tibial and femoral bone loss.

Clin Orthop, 1997 Dec, (345), 8 - 16
The Coventry Award . The value of preoperative aspiration before total knee revision; Barrack RL et al.; The value of routine aspiration of a symptomatic total knee replacement before reoperation was evaluated . The study group consisted of a consecutive series of 69 knees in 67 patients in which preoperative aspiration was performed . All aspirations were performed on an outpatient basis in a clinic setting . Local anesthetics and saline washings were not used . Twenty knees were determined to be infected and 49 knees were not infected . Preoperative aspiration had an overall sensitivity of 55%, specificity of 96%, accuracy of 84%, positive predictive value of 85%, and negative predictive value of 84% . Sixteen patients were taking antibiotics at the time of referral including 12 of 20 (60%) who had infected knees . Seven of these 12 (58%) had no growth on their initial knee aspiration . Four of these had their knees reaspirated at a later date because of a high index of suspicion for infection and the subsequent aspiration revealed the infecting organism in all four cases . Two of the remaining three patients had signs of sepsis develop and reaspiration was not performed because immediate reoperation was indicated clinically . The initial aspiration on the third patient was performed after antibiotic therapy was discontinued for 4 weeks and a repeat aspiration was not deemed necessary . When the results of the reaspirations are included, the overall aspiration results improved to a sensitivity of 75%, specificity of 96%, and accuracy of 90% . The results of the study support the use of routine preoperative aspiration before total knee revision . Previous antibiotic use increases the risk of a false negative result, and reaspiration at a later date can be expected to significantly improve the value of this test in such cases.

FEMS Microbiol Lett, 1997 Dec 1, 157(1), 137 - 40
Functional analysis of a conserved aspartate D218 in Cephalosporium acremonium isopenicillin N synthase; Loke P et al.; Isopenicillin N synthase (IPNS) is instrumental in the catalytic conversion of a tripeptide precursor delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to a bioactive intermediate isopenicillin N in the beta-lactam antibiotic biosynthetic pathway . It has recently been shown that this reaction is dependent on a conserved aspartate, D214, in a bacterial Streptomyces jumonjinensis IPNS . Thus, this study was carried out to provide the experimental evidence for the involvement of a similarly conserved aspartate residue, D218, in a fungal Cephalosporium acremonium IPNS (cIPNS) . Initially, alteration of the aspartate residue to generate the mutant D218L cIPNS protein was achieved by site-directed mutagenesis . Subsequent enzyme assays indicated that the catalytic property of the mutant protein was lost, attesting to the need for the corresponding conserved aspartate to maintain IPNS functionality . It is also evident from the observed results that site-directed mutagenesis of this particular aspartate residue in cIPNS can affect its solubility . It is therefore important to take these potential changes into consideration when site-directed mutant proteins are analysed for catalytic function.

Blood, 1997 Dec 15, 90(12), 4710 - 8
A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia . The International Acute Myeloid Leukemia Study Group; Heil G et al.; The safety and efficacy of filgrastim as an adjunct to acute myeloid leukemia (AML) induction and consolidation therapy was assessed in this prospective double-blind, randomized, placebo-controlled, multicenter trial . A total of 521 consecutive de novo AML patients aged 16 or more years were randomized to receive filgrastim (5 microg/kg/d subcutaneously) or placebo after standard induction as well as consolidation chemotherapy . Blinded study drug was given from 24 hours after chemotherapy until the absolute neutrophil count was >/=1.0 x 10(9)/L for 3 consecutive days . The overall complete remission rate was 68% . After a median follow-up of 24 months (range 5 to 40) the median disease-free survival was 10 months (95% confidence interval {CI}, 8.7 to 10.8) and the median overall survival was 13 months (95%CI, 12.2 to 14.6) . These did not differ between treatment groups . Patients receiving filgrastim experienced neutrophil recovery 5 days earlier after induction 1 than those receiving placebo (P < .0001) . This was accompanied by reductions in the duration of fever (7 v 8.5 days; P = .009), parenteral antibiotic use (15 v 18.5 days; P = .0001), and hospitalization (20 v 25 days; P = .0001) . Similar reductions were seen after induction 2 and the consolidation courses . There was a significant reduction in the number of patients requiring systemic antifungal therapy in the filgrastim group during induction treatment (34% v 43%; P = .04) . In conclusion, filgrastim is safe in that it had no negative impact on the prognosis of the AML patients . In addition, it effectively reduced the duration of neutropenia, leading to significant clinical benefits by reducing the duration of fever; requirement for parenteral anti-infectives, specifically amphotericin B; and the duration of hospitalization.

J Neurovirol, 1997 Oct, 3(5), 322 - 30
Efficient gene transfer into primary and immortalized human fetal glial cells using adeno-associated virus vectors: establishment of a glial cell line with a functional CD4 receptor; Keir SD et al.; Adeno associated virus (AAV) is a non-pathogenic dependent parvovirus with a broad host range, capable of high levels of transduction and stable integration into the host cell genome . We have investigated the potential for using AAV as a vector for gene transfer into glial cells of the human fetal nervous system . Recombinant AAV vectors expression either the reporter gene beta-galactosidase or a human CD4 receptor were able to transduce both primary glial cells of the human fetal nervous system and an SV40 immortalized human fetal glial cell line (SVG) . No difference in transduction efficiency was observed between the primary cells and the cell line which in both cases was as high as 95% . Stable transfectants of the glial cell line expressing the CD4 receptor were selected . An SVG/CD4 expressing line was then established . The presence of the CD4 receptor was confirmed by immunohistochemistry, Westerm immuno-blotting and flow cytometric analysis . The CD4 receptor was shown to be functional by infection of the SVG/CD4 cell line with the human immunodeficiency virus (HIV) . Upon infection, the SVG/CD4 cells produced 20-fold higher levels of the HIV intracellular core antigen P24 than the CD4 negative parental cells and in addition formed syncytia . The use of AAV vectors should prove useful in biological investigations of human glial cells and offers promise as a means of ex vivo and in vivo gene delivery.

Mol Gen Genet, 1997 Nov, 256(5), 488 - 98
Molecular and functional analysis of the ribosomal L11 and S12 protein genes (rplK and rpsL) of Streptomyces coelicolor A3(2); Ochi K et al.; A RelC deletion mutant, KO-100, of Streptomyces coelicolor A3(2) has been isolated from a collection of spontaneous thiostrepton-resistant mutants . KO-100 grows as vigorously as the parent strain and possesses a 6-bp deletion within the rplK, previously termed relC . When the wild-type rplK gene was propagated on a low-copy-number vector in mutant KO-100, the ability to produce ppGpp, actinorhodin and undecylprodigiosin, which had been lost in the RelC mutant, was completely restored . Allele replacement by gene homogenotization demonstrated that the RelC mutation is responsible for the resistance to thiostrepton and the inactivation of ppGpp, actinorhodin and undecylprodigiosin production . Western blotting showed that ribosomes from the RelC mutant KO-100 contain only one-eighth the amount of L11 protein found in ribosomes of the parent strain . The impairment of antibiotic production in KO-100 could be rescued by the introduction of mutations that confer resistance to streptomycin (str), which result in alteration of Lys-88 in ribosomal protein S12 to Glu or Arg . No accompanying restoration of ppGpp synthesis was detected in these RelC str double mutants.

Arch Otolaryngol Head Neck Surg, 1997 Dec, 123(12), 1271 - 5
Relative incidence and alternative approaches for surgical drainage of different types of deep neck abscesses in children; Choi SS et al.; OBJECTIVES: To determine the relative frequency of retropharyngeal abscesses (RPAs) vs lateral pharyngeal abscesses (LPAs) and to analyze alternative approaches for surgical drainage . DESIGN: Retrospective chart review . SETTING: Tertiary care children's hospital . PATIENTS: Seventy pediatric patients who were evaluated, admitted, and treated for presumed deep neck abscesses (RPAs and LPAs) between January 1, 1986, and December 31, 1996 . INTERVENTION: Intravenous antibiotic therapy and surgical drainage . MAIN OUTCOME MEASURE: Clinical resolution of the abscess . RESULTS: Fifty-eight patients were evaluated with computed tomographic scan . Thirteen of these patients did not have surgical intervention . Of 12 patients diagnosed as having an isolated RPA, all had intraoral surgical drainage and 9 had evidence of pus at surgery . Twenty-one patients had an isolated LPA . Sixteen of these underwent intraoral drainage and 5 underwent external drainage . Purulence was found at surgery in 14 and 2 patients, respectively . The remaining 12 patients had a combination of RPA and LPA . Eight patients underwent intraoral drainage, and 4 patients required both intraoral and external approaches . Purulence was found at surgery in 5 and 4 patients, respectively . Of the 12 patients who were not evaluated with computed tomographic scan, two thirds were treated prior to 1987 . Six of these 12 patients underwent surgical drainage via an intraoral approach, and 4 of the 6 patients had pus . The remaining 6 improved without surgery . CONCLUSIONS: Most deep neck abscesses in children are located in the retropharyngeal or in the lateral pharyngeal space medial to the great vessels . Therefore, most can be managed successfully with intraoral rather than external drainage . External approaches are better reserved for those abscesses that are lateral to the great vessels or that involve multiple spaces . In this patient population, LPAs were more commonly seen than RPAs.

Antibiot Khimioter, 1997, 42(8), 21 - 5
{Screening of drugs inhibiting cholesterol synthesis}; Bibikova MB; The biosynthesis of fusidin, an antibiotic of steroid structure, was used as a model of steroid synthesis . Screening of compounds modifying the fusidin synthesis included 80 strains of mycelial fungi . A high frequency of such fungal cultures was observed . 9 cultures forming compounds which inhibited the synthesis of cholesterol in the cell culture of human hepatocytes were screened . A method for biological estimation of the activity of cholesterol synthesis inhibitors was developed on rabbits with high blood levels of cholesterol . It was shown that the cholesterol synthesis inhibitors, isolated as a result of the specific screening were not toxic and markedly lowered the cholesterol blood levels.

Antibiot Khimioter, 1997, 42(10), 33 - 7
{Isolation and biological characterization of Legionella pneumophila mutants resistant to aminoglycoside antibotics and their protective action}; Marakusha BI et al.; Preliminary estimation of virulence in some antibiotic resistant mutants of Legionella pneumophila, Philadelphia 1 in various models of infection revealed its decrease in the mutants resistant to azlocillin, cefotaxime, fluoroquinolone LIB-80, neamine and streptomycin . Detailed investigation of the neamine resistant mutants showed that in relation to streptomycin susceptibility such mutants could be divided into 3 classes: susceptible to streptomycin, resistant to high concentrations of streptomycin and resistant to moderate concentrations of streptomycin . Part of mutants Nea(r)Strr and Nea(r)Strr500 and all mutants Nea(r)Strr100 proved to be less virulent with respect to guinea pigs and chick embryos . The study of the spectinomycin resistant mutants of Legionella spp . did not reveal any changes in the virulence which made it possible to suggest that the influence of the mutations in the ribosomal protein genes determining resistance to streptomycin and neamine on virulence of L . pneumophila was based on the interdependence of the mutant effect on the suppression and the influence on the virulence detected by us in S . flexneri, Y . pseudotuberculosis, L . monocytogenes and F . tularensis . The Legionella mutants Nea(r)Strr100 were characterized by significant protective activity and protected immunized guinea pigs when tested in a model of their aerogenic infection.

Ann Intern Med, 1997 Dec 1, 127(11), 985 - 8
Effect of fluoroquinolone on the enhanced nitric oxide-induced peripheral vasodilation seen in cirrhosis; Chin-Dusting JP et al.; BACKGROUND: In patients with cirrhosis, portosystemic shunts allow intestinal bacteria and endotoxin to enter the systemic circulation . Endotoxemia may induce increased synthesis of nitric oxide, thereby contributing to arterial vasodilation . OBJECTIVE: To test the hypothesis that the antibiotic norfloxacin blocks the effects of nitric oxide . DESIGN: Placebo-controlled, double-blind, crossover study . SETTING: Alfred Hospital, Melbourne, Australia . PATIENTS: 9 patients with alcohol-related cirrhosis and 10 healthy controls . INTERVENTION: Norfloxacin, 400 mg twice daily, for 4 weeks . MEASUREMENTS: Peripheral blood flow was measured by using forearm venous occlusion plethysmography . RESULTS: Basal forearm blood flow was higher in patients with cirrhosis than in controls (3.69 +/- 0.27 mL/100 mL per minute and 2.47 +/- 0.40 mL/100 mL per minute; P = 0.014) but returned toward normal after norfloxacin was given (2.64 +/- 0.31 mL/100 mL of tissue per minute in patients with cirrhosis) . Responses to NG-monomethyl-L-arginine were greater in patients with cirrhosis but returned to normal after norfloxacin was given . CONCLUSION: Bacterial endotoxemia in patients with cirrhosis induces increased synthesis of nitric oxide that can be corrected with norfloxacin.

Zentralbl Chir, 1997, 122(8), 681 - 9
{Changes in therapeutic principles in fractures of the extremities with severe soft tissue injuries exemplified by tibial fracture}; David A et al.; Functional results after open fractures have been improved during the last decades . Especially the rates of amputation and chronic osteitis after open tibial fractures have been reduced from 30% to less than 5% . The initial management of this type of fracture includes reconstruction of the perfusion of the involved vessels, subsequent debridement with resection of avascular tissues, decompression of compartments by fasciotomy and initial shortening of the tibia by osteotomy and followed by callus distraction in order to achieve the physiological length of the leg . Cortical bone with periostal stripping has to be covered by local muscle transfer or by free vascularized tissue transfer within 3-7 days . Bone defects are either reconstructed by cancellous bone graft or, if the defect is longer than 2 cm, by continuous segmental transfer, according to the technique described by Ilizarov.

Urol Nefrol (Mosk), 1997 Sep-Oct, (5), 5 - 9
{The membrane phospholipid peroxidation and Ca-dependent ATPase activity of the microsomal fractions isolated from rat renal tissue in thermal ischemia with and without alpha-tocopherol protection}; Golod EA; The author studied the effects of 30-min heat ischemia of rat kidneys on the level of malonic dialdehyde (MDA) and Ca-dependent ATPase activity of microsomal fraction isolated from the cortical substance in the presence and absence of antibiotic alameticine and ortovandate in the incubation medium and protective action on Ca-ATPase activity of rat pretreatment with alpha-tocopherol (TP) . It has been demonstrated that thermal ischemia induces inhibition of Ca-ATPase activity of microsomes resistant to vanadate . Administration of TP reduced MDA level, enhanced Ca-ATPase microsomal activity in the presence of alameticine against inhibition of enzymic activity in the absence of alameticine . This indicates a rise in the true enzyme activity under decreasing membrane permeability in conditions of diminishing activity of lipid peroxidation in response to TP effects.

Przegl Epidemiol, 1997, 51(3), 309 - 15
{Nitric oxide (NO) in children with meningitis}; Murawska E et al.; Twenty seven children with a documented bacterial (BM)-, 73 with viral (mumps and enteroviral) meningitis and 51 controls were included . CSF white blood cell counts, glucose and protein concentrations were determined routinely . CSF nitrite and nitrate levels (the stable degradation product of NO) were determined by a modified Griess reaction . The mean +/- levels of nitrite and nitrate in CSF on admission were higher in patients with BM in comparison with controls and in children with viral meningitis . In 10 patients dexamethasone therapy was started about 10 minutes before the first antibiotic dose and given every 12 hours of 0.4 mg/kg for 2 days . At 24 to 48 hours those who received dexamethasone therapy had a significantly lower mean +/- SD CSF nitrite concentration compared with that in non-steroid treated patients . In all patients with meningitis a significant positive correlation was found between CSF nitrite and CSF granulocyte counts and also CSF protein concentration . Increased production of NO in the CSF compartment during the acute phase of BM may contribute to the inflammatory process and tissue injury . Dexamethasone therapy administered before the first parenteral antibiotic dose reduces the production of NO in the CSF during BM.

Orv Hetil, 1997 Oct 12, 138(41), 2609 - 11
{Artificial nutrition of patients with toxic epidermal necrolysis (Lyell syndrome)}; Kertai M et al.; The authors report the case of a 30-year-old man treated with toxic epidermal necrolysis . Toxic epidermal necrolysis was due to anticonvulsive drug treatment . The patient was admitted with denudated skin surface similar to second-degree burn that covered 90 per cent of the patient's body surface . The patient was isolated and treated, receiving sterile wound care, broad spectrum antibiotic and corticosteroid . Total parenteral nutrition was instituted until the 5th day of care because the patient was unable to take normal food . The energy intake reached 146 kJ/kg bodyweight containing 4 g/kg bodyweight carbohydrates and 2 g/kg bodyweight fat emulsion supplemented with 10-15 g of nitrogen per day . The enteral nutrition was commenced gradually with decreasing parenteral nutrition . The nutritive solutions were supplemented with ions, vitamins and trace elements . The patient left the intensive care unit after 23 days of care . The toxic epidermal necrolysis is a life-threatening dermatological disease and should be treated at intensive care unit . The early recognition of the disease, the intensive care and nutritional therapy may improve the survival of patients with toxic epidermal necrolysis.

Mund Kiefer Gesichtschir, 1997 Mar, 1(2), 121 - 4
{Osteomyelitis of the facial skull in Albers-Schönberg osteopetrosis}; Ozmen Y et al.; Albers-Schonberg osteopetrosis, a rare heritable bone disease with autosomal dominant or recessive transmission, is generally characterised by diffuse sclerosis of the whole skeleton accompanied by pathological bone fragility and delayed physical development, profound intractable myelophthisic anaemia, neurological deficits, and osteomyelitis, especially of the jaws and the skull . The precise aetiology of the osteopetrosis is not clear . Therefore therapy is restricted to alleviation of symptoms . In this study the case of a patient suffering from the benign form of osteopetrosis is presented . Osteomyelitis of the skull was treated successfully 2 years after the removal of lower and upper jaw teeth by a combined multistage surgical and antibiotic approach.

Gastroenterol Hepatol, 1997 Oct, 20(8), 412 - 4
{Psoas abscess in Crohn's disease . Preoperative evaluation and surgical attitude}; Acea Nebril B et al.; Three patients with psoas abscess secondary to Crohn's diseases are reported with the aim of discussing the diagnosis and surgical management of these patients . It is concluded that computerized tomography is the method of choice for the diagnosis and follow up of this complication . Surgery should be individualized but in stable patients abscess drainage should be attempted in addition to resection of the intestine involved . Finally, given the great risk of pulmonary thromboembolism in these patients, intensive prophylactic anticoagulant therapy is required.

Aktuelle Radiol, 1997 Sep, 7(5), 239 - 42
{Minimally invasive treatment of abscesses by CT-controlled drainage with a basket catheter system}; Muller RD et al.; PURPOSE: To examine whether the percutaneous drainage of abscess formations by a new basket catheter system is usefull . MATERIAL AND METHODS: 58 patients with abscesses in different locations and origins have been treated by an interventional radiologic procedure . On the whole 77 basket-catheters were placed under CT-guidance into abscess formations of different size and localization . 36 patients developed an abscess after surgery, two patients achieved abscess drainage after embolisation of a tumor . In 20 patients the abscess was a complication of a septic infectious disease . RESULTS: Open surgery was avoided in 41/58 patients of these patients 9/41 received only percutaneous drainage and 32/41 patients suffering from illness were given antibiotic medication according to the resistogram in combination with percutaneous drainage . 17/58 patients required secondary surgery but with a lower risk because of the smaller abscess volume and the better clinical constitution after percutaneous drainage . CONCLUSIONS: A minimally invasive management of abscesses using a basket-catheter system is successful even in localisations deep inside the body and hard to reach . An irreversible catheter occlusion followed by the implantation of a new catheter system could be avoided in all patients.

Clin Exp Immunol, 1997 Dec, 110(3), 479 - 84
Protection from concanavalin A (Con A)-induced T cell-dependent hepatic lesions and modulation of cytokine release in mice by sodium fusidate; Nicoletti F et al.; The immunomodulatory effects of the antibiotic sodium fusidate (SF) were tested in a model of T cell-dependent hepatic injury that can be induced in normal mice by a single i.v . injection of Con A . Signs of hepatitis with elevated transaminase activities in plasma, severe infiltration of the liver by neutrophil granulocytes, lymphocytes and monocytes, and necrotic areas were observed in control mice treated intraperitoneally with PBS 24 h and 1 h before Con A challenge . T cell- and macrophage-derived cytokines (IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha, IL-1beta, IL-6) were released with different kinetics in the circulation of these mice . SF, 20, 40 or 80 mg/kg, administered 24 h and 1 h before Con A challenge, protected the mice against the hepatitic effects of Con A . The protective effects of SF were dose-dependent and accompanied by profound modifications of blood levels of cytokines induced by Con A, so that, relative to control mice, SF (80 mg/kg)-treated animals showed markedly diminished plasma levels of IL-2, IFN-gamma and TNF-alpha, along with augmented levels of IL-6 . These results suggest that SF might be useful in the treatment of immunoinflammatory liver diseases in humans.

Am J Surg, 1997 Dec, 174(6), 733 - 5; discussion 735-6
Medical versus surgical management of diverticulitis in patients under age 40; Cunningham MA et al.; BACKGROUND: Diverticulitis in patients under age 40 is a distinct entity . We compared the medical versus surgical management of diverticulitis for complications and outcomes in these patients . METHODS: A retrospective review was performed for treatment, hospitalizations, complications, and outpatient visits . Complications included readmission, recurrent symptoms after antibiotic therapy, and postoperative problems . RESULTS: Twenty-nine patients had a radiographic or surgical diagnosis of diverticulitis (18 surgical, 11 medical) . Medically managed patients had significantly more emergency department visits (4.7 +/- 6.6 versus 0.3 +/- 0.6, P < or =0.01), and readmissions (7 versus 4, P < or =0.02) . Three surgical patients (17%) had a total of 6 complications as compared with 6 medical patients (55%) with 25 complications (chi square, P < or =0.05) . All medically treated patients had recurrent symptoms, and 6 required surgery . CONCLUSION: Medically managed patients had significantly more emergency department visits and complications than those managed surgically . Surgery is the indicated treatment for the first episode of diverticulitis in patients under age 40.

Neurology, 1997 Dec, 49(6), 1661 - 70
Reversible cerebral hypoperfusion in Lyme encephalopathy; Logigian EL et al.; Lyme encephalopathy (LE) presents with subtle neuropsychiatric symptoms months to years after onset of infection with Borrelia burgdorferi . Brain magnetic resonance images are usually normal . We asked whether quantitative single photon emission computed tomography (SPECT) is a useful method to diagnose LE, to measure the response to antibiotic therapy, and to determine its neuroanatomic basis . In 13 patients with objective evidence of LE, SPECT demonstrated reduced cerebral perfusion (mean perfusion defect index {PDI} = 255), particularly in frontal subcortical and cortical regions . Six months after treatment with 1 month of intravenous ceftriaxone, perfusion significantly improved in all 13 patients (mean PDI = 188) . In nine patients with neuropsychiatric symptoms following Lyme disease, but without objective abnormalities (e.g., possible LE), perfusion was similar to that of the treated LE group (mean PDI = 198); six possible LE patients (67%) had already received ceftriaxone prior to our evaluation . Perfusion was significantly lower in patients with LE and possible LE than in 26 normal subjects (mean PDI = 136), but 4 normal subjects (15%) had low perfusion in the LE range . We conclude that LE patients have hypoperfusion of frontal subcortical and cortical structures that is partially reversed after ceftriaxone therapy . However, SPECT cannot be used alone to diagnose LE or determine the presence of active CNS infection.

Acta Chir Hung, 1997, 36(1-4), 174 - 5
Improvement of swallowing ability in advanced oesophageal cancer; Kovacs I et al.; Without different types of palliation the patients with inoperable oesophageal cancer have a poor quality of life, rapid weight loss which leads to death . The aim of palliation is the complete relief of dysphagia . Our modified procedure is a simplified way of a well known method described by Tytgat in 1986 . The prosthesis is positioned under continuous visual control using only local anaesthesia . This method is safe and not expensive . During the last three years 73 consecutive patients were treated with palliative fiberoscopic intubation with Tygon prosthesis . 46 patients had esophageal carcinoma, 19 had gastric, 8 had pulmonary carcinoma obstructing the gullet . Among them 11 patients had bronchoesophageal fistula . The early complications were perforations (7) bleeding (2), and later complications: food impaction (5) tumor overgrowth (5) and tube migration (2) . The mortality was 2% . All patients have received antibiotic prevention . Although the improvement of life quality is more important than extension of life, for many patients survival will be prolonged due to improved nutrition as a result of treatment . This study summaries our experience with this technique and analyzes the problems and complications encountered in our patients.

Sex Transm Dis, 1997 Nov, 24(10), 573 - 5
Screening of sex workers in Turkey for Chlamydia trachomatis; Agacfidan A et al.; BACKGROUND: Increasing migration of sex workers across East European borders into Turkey has resulted in increased arrests of unregistered sex workers . There is concern regarding the prevalence of sexually transmitted diseases (STD) such as C . trachomatis in this unregulated group . OBJECTIVE: To measure the prevalence of C . trachomatis infection and selected related demographic and behavioral factors among registered and unregistered sex workers in Istanbul, Turkey . METHODS: In a cross-sectional study, the prevalence of C . trachomatis infection was studied by direct fluorescent antibody testing in 248 sex workers: 158 presented for routine medical screening and 90 who were arrested for lack of registration . All subjects were interviewed regarding demographic factors, sexual activity, and antibiotic and drug use . RESULTS: The overall C . trachomatis prevalence was 12.9% (12.0% registered and 14.4% unregistered) . There was a strong association between never using condoms and chlamydia positivity (odds ratio 8.9 {95% confidence interval 3.7 to 21.6}) . CONCLUSIONS: The high rate of C . trachomatis among all tested sex workers and the lack of regular condom use, particularly among unregistered sex workers, indicate that there is an urgent need for safe sex education and continued STD screening of unregistered sex workersPIP: Accelerating migration of unregistered sex workers from Eastern European countries to Turkey has produced alarm about the potential for increased sexually transmitted disease (STD) transmission . Licensed sex workers are routinely screened for STDs and given medical examinations . However, in Turkey, women with foreign citizenship are ineligible for licensing . This cross-sectional study measured the prevalence of Chlamydia trachomatis in 248 sex workers in Istanbul in 1993 . 158 sex workers were enrolled when they presented for routine medical screening, while 90 (from Rumania) were arrested for lack of registration . The overall C . trachomatis prevalence, as detected by direct fluorescent antibody testing, was 12.9% (12.0% among registered and 14.4% among unregistered women); however, the fact that almost half these women reported recent self-prescribed antibiotic use suggests these rates are underestimates . When the analysis was restricted to the 84 women without recent antibiotic use, the C . trachomatis prevalence was 36.9% . There was a significant association between never using condoms and chlamydia infection (odds ratio, 8.9; 95% confidence interval, 3.7-21.6) . These findings suggest a need for safe sex education and continued STD screening of sex workers in Turkey . Eligibility for registration, regardless of nationality, should be reconsidered for public health reasons .

W V Med J, 1997 Sep-Oct, 93(5), 260 - 3
Childhood acute rheumatic fever: a comparison of recent resurgence areas to cases in West Virginia; Hoffman TM et al.; A resurgence of acute rheumatic fever (ARF) was noted over the last 10 years in several areas of the United States . West Virginia was no exception with two reports appearing in the literature confirming an increased incidence in the 1980s among children and adults . The Pediatric Cardiology Division of West Virginia University Children's Hospital had 30 cases of ARF referred between 1980 and 1995, and surprisingly 27 of these cases had been diagnosed since 1986 . This article describes our chart review of these 30 cases which studied epidemiological aspects, diagnostic criteria and regional differences by chi-square analysis . Other issues we present include "silent" mitral regurgitation and the unreliability of a history of a recent pharyngitis with or without appropriate antibiotic therapy while considering ARF in the differential diagnosis.

Chem Biol, 1997 Oct, 4(10), 751 - 5
Folding of the polyketide chain is not dictated by minimal polyketide synthase in the biosynthesis of mithramycin and anthracycline; Kantola J et al.; BACKGROUND: Mithramycin, nogalamycin and aclacinomycins are aromatic polyketide antibiotics that exhibit antitumour activity . The precursors of these antibiotics are formed via a polyketide biosynthetic pathway in which acetate (for mithramycinone and nogalamycinone) or propionate (for aklavinone) is used as a starter unit and nine acetates are used as extender units . The assembly of building blocks is catalyzed by the minimal polyketide synthase (PKS) . Further steps include regiospecific reductions (if any) and cyclization . In the biosynthesis of mithramycin, however, ketoreduction is omitted and the regiospecificity of the first cyclization differs from that of anthracycline antibiotics (e.g . nogalamycin and aclacinomycins) . These significant differences provide a convenient means to analyze the determinants for the regiospecificity of the first cyclization step . RESULTS: In order to analyze a possible role of the minimal PKS in the regiospecificity of the first cyclization in polyketide biosynthesis, we expressed the mtm locus, which includes mithramycin minimal PKS genes, in Streptomyces galilaeus, which normally makes aclacinomycins, and the sno locus, which includes nogalamycin minimal PKS genes, in Streptomyces argillaceus, which normally makes mithramycin . The host strains are defective in the minimal PKS, but they express other antibiotic biosynthesis genes . Expression of the sno minimal PKS in the S . argillaceus polyketide-deficient strain generated mithramycin production . Auramycins, instead of aclacinomycins, accumulated in the recombinant S . galilaeus strains, suggesting that the mithramycin minimal PKS is responsible for the choice of starter unit . We also describe structural analysis of the compounds accumulated by a ketoreductase-deficient S . galilaeus mutant; spectroscopic studies on the major polyketide compound that accumulated revealed a first ring closure which is not typical of anthracyclines, suggesting an important role for the ketoreductase in the regiospecificity of the first cyclization . CONCLUSIONS: These experiments clearly support the involvement of ketoreductase and a cyclase in the regiospecific cyclization of the biosynthetic pathway for aromatic polyketides.

Biochemistry, 1997 Nov 11, 36(45), 13904 - 9
Crystal structure of the Escherichia coli peptide deformylase; Chan MK et al.; Protein synthesis in bacteria involves the formylation and deformylation of the N-terminal methionine . As eukaryotic organisms differ in their protein biosynthetic mechanisms, peptide deformylase, the bacterial enzyme responsible for deformylation, represents a potential target for antibiotic studies . Here we report the crystallization and 2.9 A X-ray structure solution of the zinc containing Escherichia coli peptide deformylase . While the primary sequence, tertiary structure, and use of coordinated cysteine suggest that E . coli deformylase belongs to a new subfamily of metalloproteases, the environment around the metal appears to have strong geometric similarity to the active sites of the thermolysin family . This suggests a possible similarity in their hydrolytic mechanisms . Another important issue is the origin of the enzyme's specificity for N-formylated over N-acetylated substrates . Based on the structure, the specificity appears to result from hydrogen-bonding interactions which orient the substrate for cleavage, and steric factors which physically limit the size of the N-terminal carbonyl group.

Leuk Lymphoma, 1997 Sep, 27(1-2), 65 - 75
Growth factor administration following autologous peripheral blood progenitor cell transplantation; Pierelli L et al.; Hematopoietic growth factor (HGF) administration following autologous peripheral blood progenitor cell transplantation (APBPCT) is a current approach for shortening the duration of high-dose chemotherapy-induced transient peripheral pancytopenia . Several published clinical experiences and a retrospective study reported here show that recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration potentiates polymorphonuclear leukocyte (PMN) and white blood cell (WBC) recovery with some clinical benefits mainly related to the reduction of infectious complications during the shortened period of neutropenia . However, this therapeutic strategy does not produce any enhancement of platelet (PLT) recovery or potentiation of red cell production . Conversely, a recent phase I/II study carried out in our institution showed that the combined administration of rhG-CSF and recombinant human erythropoietin (rhEPO) is able to potentiate trilineage hematopoietic recovery with a reduction of PLT transfusions and to considerably simplify the clinical management of patients as compared to patients treated with APBPCT alone . The post-APBPCT administration of rhEPO with rhGM-CSF decreased the number of days with WBC < 1 x 10(9)/L but failed to produce any appreciable effect on PLT recovery . Both combined treatments significantly reduced the patients' hospital stay and allowed the abrogation of systemic antibiotic administration following APBPCT . A further group of patients were treated with the combined administration of rhEPO, rhG-CSF and rhGM-CSF; they did not show a faster hematopoietic recovery than rhG-CSF plus EPO treated patients and a consistent hyperthermia was observed in most patients as a prominent side effect . Future prospective randomized studies will clarify the efficacy of HGF administration following APBPCT . Moreover, further improvements in the hematopoietic support of transplanted patients may be obtained when stem cell factor, flt3/flk2 tyrosine kinase ligands or megakaryocyte growth and development factor will become clinically available.

Curr Opin Hematol, 1996 Jan, 3(1), 3 - 10
American Society of Clinical Oncology guidelines for the use of hematopoietic colony-stimulating factors; Ozer H; The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce the likelihood of neutropenic complications due to chemotherapy . Clinical benefit has been shown, but the high cost of colony-stimulating factors has led to concern about their appropriate use . The American Society of Clinical Oncology has established evidence-based, clinical practice guidelines for the use of colony-stimulating factors in patients who are not enrolled in clinical trials . An expert multidisciplinary panel reviewed the clinical data documenting the activity of colony-stimulating factors . For each common clinical situation, the panel formulated a guideline to encourage reasonable use of colony-stimulating factors to preserve effectiveness but discourage excess use when little marginal benefit is anticipated . Outcomes considered in evaluating colony stimulating factor benefit included duration of neutropenia, incidence of febrile neutropenia, incidence and duration of antibiotic use, frequency and duration of hospitalization, infectious mortality, chemotherapy dose intensity, chemotherapy efficacy, quality of life, colony-stimulating factor toxicity, and economic impact . To the extent that these data were available, the panel placed greatest value on survival benefit, reduction in rates of febrile neutropenia, decreased hospitalization, and reduced costs . Lesser value was placed on alterations in absolute neutrophil counts.

J Neurosci, 1997 Dec 1, 17(23), 8955 - 63
Inhibition of axonal growth by brefeldin A in hippocampal neurons in culture; Jareb M et al.; The outgrowth of neuronal processes involves a great increase in the surface area of the cell . The supply of membrane material necessarily must be coordinated with the demands for neurite growth . The selective growth of only one or two neurites at any given time during the development of polarity raises the possibility that the production of materials by the soma is limiting for growth (Dotti and Banker, 1987; Dotti et al., Goslin and Banker, 1990) . To examine the role of the availability of membrane components during the development of polarity and axonal elongation, we treated neurons with brefeldin A, an antibiotic that disrupts the trafficking of vesicles from the Golgi complex to the plasma membrane . Treatment with brefeldin A (1 microg/ml) inhibited axonal growth within 0.5 hr; in unpolarized cells it prevented the formation of an axon . These results indicate that the availability of membrane components of Golgi-derived vesicles is required for axonal growth and hence the development of polarity . Inhibitors of protein and RNA synthesis also blocked axonal growth and the development of polarity, but over a much slower time course . This suggests that the full complement of proteins and mRNAs required for the initial development of polarity is present for several hours before polarity is actually established.

J Neurol Sci, 1997 Oct 22, 151(2), 163 - 7
Alteration of cytokine levels by fosfomycin and prednisolone in spontaneous proliferation of cultured lymphocytes from patients with HTLV-I-associated myelopathy (HAM/TSP); Yamano Y et al.; Fosfomycin has recently been reported as an antibiotic with immunomodulatory activities . To evaluate the possibility of clinical administration of fosfomycin in patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the effects of this agent on the HTLV-I-induced in vitro phenomenon were studied . The influence of fosfomycin on in vitro spontaneous proliferation (SP) of peripheral blood mononuclear cells (PBMCs) from four patients with HAM/TSP was measured by thymidine incorporation into the cells, and the concentration of several cytokines in the culture supernatants was examined in three HAM/TSP patients . Enzyme-linked immunosorbent assays (ELISAs) were employed to detect the concentrations of interleukin-4 (IL-4), IL-6, IL-10, interferon-gamma (IFN-gamma), transforming growth factor-beta1 (TGF-beta1), and macrophage inflammatory protein-1alpha (MIP-1alpha) . The data were compared to the changes by prednisolone which is known to regulate the HTLV-I-associated in vitro phenomenon and to have a therapeutic benefit in patients with HAM/TSP . Production of IL-6, IFN-gamma and MIP-1alpha from the spontaneously proliferating cells were demonstrated . Fosfomycin could not suppress the HTLV-I-associated SP, but had the properties to decrease the levels of TGF-beta1 and MIP-1alpha . It was also demonstrated that the concentrations of IFN-gamma and MIP-1alpha in the cultures in the presence of prednisolone were apparently decreased, suggesting a possible involvement of these cytokines in the pathogenesis of HAM/TSP . These findings support the hypothesis that fosfomycin may have immunomodulatory potentials in HTLV-I-related cellular interactions in a different manner from ordinary immunomodulatory agents.

Postgrad Med, 1997 Dec, 102(6), 45 - 7, 52, 55-62
Community-acquired pneumonia . Tailoring management of adult patients according to risk category; Rubins JB et al.; A cost-conscious evaluation of CAP in the adult patient requires an initial assessment of the clinical severity and the risks of complicated pneumonia . Initially, most patients should have chest radiography; some authorities also recommend sputum Gram staining and culture, but additional blood testing, culture, and diagnostic procedures are indicated only for patients who have chronically impaired health or clinical evidence of sever infection . Initial empirical antibiotic therapy varies depending on the setting (outpatient, hospitalized patient, critically ill patient) . Failure of the patient to respond to empirical antibiotic therapy within 72 hours should direct the clinician to consider unusual or resistant organisms or noninfectious causes of pneumonitis.

Oncol Res, 1997, 9(6-7), 333 - 7
A new cellular target for mitomycin C: a case for mitochondrial DNA; Pritsos CA et al.; Mitomycin C (MMC) is an anticancer, antibiotic that is currently used clinically against a wide variety of tumors . Nuclear DNA is regarded as the primary cellular target for mitomycin's toxicity . In this study, the effect of MMC on mitochondrial DNA was tested both in vitro and in vivo . EMT6 mouse mammary carcinoma cells were treated with MMC and conformational changes in their mitochondrial DNA were determined as a measure of mitochondrial DNA damage . A dose-dependent relationship was observed between MMC treatment dosages and mitochondrial DNA damage . Liver tissue mitochondria from Balb/c mice treated with MMC were assayed for mitochondrial integrity . Mitochondrial integrity was lowered in the MMC-treated animals . Liver tissue adenosine triphosphate (ATP) levels were also shown to be significantly decreased in these same animals . We also show that MMC can be activated by mitochondria . These studies provide strong evidence that mitochondrial DNA is a target for MMC and that this interaction has a biochemical consequence that could prove toxic.

JAMA, 1997 Dec 17, 278(23), 2080 - 4
Quality of care, process, and outcomes in elderly patients with pneumonia; Meehan TP et al.; CONTEXT: Pneumonia is a frequent cause of hospitalization and death among elderly patients, but the relationships between processes of care for pneumonia and outcomes are uncertain, making quality improvement a challenge . OBJECTIVES: To assess quality of care for Medicare patients hospitalized with pneumonia and to determine whether process of care performance is associated with lower 30-day mortality . DESIGN: Multicenter retrospective cohort study with medical record review . SETTING: A total of 3555 acute care hospitals throughout the United States . PATIENTS: A total of 14069 patients at least 65 years old hospitalized with pneumonia . MAIN OUTCOME MEASURES: Four processes of care: time from hospital arrival to initial antibiotic administration; blood culture collection before initial hospital antibiotics; blood culture collection within 24 hours of hospital arrival; and oxygenation assessment within 24 hours of hospital arrival . Associations between processes of care and 30-day mortality were determined with logistic regression analysis . RESULTS: National estimates of process-of-care performance were antibiotic administration within 8 hours of hospital arrival, 75.5% (95% confidence interval {CI}, 73.1-77.9); blood cultures before antibiotics, 57.3% (95% CI, 54.5-60.1); initial blood culture collection, 68.7% (95% CI, 66.2-71.2); and initial oxygenation assessment, 89.3% (95% CI, 87.5-90.9) . Lower 30-day mortality was associated with antibiotic administration within 8 hours of hospital arrival (odds ratio {OR}, 0.85; 95% CI, 0.75-0.96) and blood culture collection within 24 hours of arrival (OR, 0.90; 95% CI, 0.81-1.00) . State and territory performance estimates varied from 49.0% to 89.7% for antibiotics given within 8 hours and from 45.6% to 82.6% for blood cultures drawn within 24 hours . CONCLUSIONS: Administering antibiotics within 8 hours of hospital arrival and collecting blood cultures within 24 hours were associated with improved survival . The fact that states varied widely in the performance of these measures suggests that opportunities exist to improve hospital care of elderly patients with pneumonia.

Dermatology, 1997, 195 Suppl 2, 89 - 92
Cytotoxicity and sensitization of povidone-iodine and other frequently used anti-infective agents; Niedner R; Povidone-iodine is an antiseptic widely used in dermatology . In vitro experiments showed a certain cytotoxicity, yet it is not easy to transfer these toxicological data to in vivo circumstances . In vivo investigations in animals and in humans could exclude cytotoxic effects of povidone-iodine, measured by the wound healing process . Only when administered in combination with detergents was an obvious cytotoxicity seen in wounds but not on the intact skin . In comparison to the frequently used antibiotic neomycin, the sensitization rate of povidone-iodine is very low.

Dermatology, 1997, 195 Suppl 2, 53 - 6
Vaginal antisepsis for hysterectomy: a review of the literature; Eason EL; Infectious complications of hysterectomy remain common despite the use of prophylactic antibiotics . Most are caused by contamination of the surgical site by vaginal bacteria which are not controlled by current methods of pre-operative antisepsis . The medical literature concerning antiseptic preparation of the vagina for surgery was reviewed to discover the evidence on which practice may be based . A search using Medline, Current Contents, the Cochrane Library and the reference lists of articles on the subject and of major gynaecology textbooks produced 13 comparative studies . No conclusive randomized controlled trials were found and most of the studies had severe methodological problems limiting interpretation of their results . The scant available data suggest that use of vaginal antiseptics before the patient arrives in the operating room is probably not useful, and that application of povidone-iodine vaginal gel at the beginning of abdominal hysterectomy is sufficiently promising to justify further investigation.

Mutat Res, 1997 Nov 19, 381(1), 117 - 29
Proposed mechanism for the photodynamic generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine produced in cultured cells by exposure to lomefloxacin; Rosen JE; In this study, lomefloxacin (LMX), a widely used quinolone antibiotic with a high frequency of clinical phototoxicity, was investigated by measuring the effects of several antioxidants on its ability to form of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in cultured adult rat liver cells after exposure to UVA . In the current study the observed DNA damage, reflected by the formation of 8-oxo-dG, was almost completely inhibited by co-incubation of LMX and cultured cells with sodium azide (NaN3) that specifically quenches singlet oxygen . Vitamin E (alpha-tocopherol), known to quench both superoxide and singlet oxygen, inhibited 8-oxo-dG formation by approximately 54% . Mannitol, a hydroxyl radical scavenger, inhibited 8-oxo-dG formation by 64% . Butylated hydroxyanisole (BHA), a scavenger of hydroxyl, peroxy and alkoxy radicals, showed no inhibition of 8-oxo-dG formation but in fact enhanced levels of 8-oxo-dG by 169% . The results of this study suggest that the mechanism for the photodynamic generation of 8-oxo-dG by LMX is mediated, at least in part, by both singlet oxygen and hydroxyl radical and involves both type I and type II photosensitization.

J Antibiot (Tokyo), 1997 Oct, 50(10), 866 - 73
Chemical synthesis and structural study of lincomycin sulfoxides and a sulfone; Sztaricskai F et al.; Oxidation of lincomycin with dimethyldioxirane resulted in the sulfoxide-glycosides 3a and 3b, whose treatment with osmium tetraoxide and N-methylmorpholine-N-oxide afforded the same sulfone; 4 . According to FAB-MS and CD investigations, the absolute configuration of the sulfur atom in 3a and 3b is R and S, respectively . The new, unsaturated antibiotic analog (6) derived from clindamycin exists in the 4C1 conformation . The antibiotic activities of the synthesized compounds were also studied.

J Antibiot (Tokyo), 1997 Oct, 50(10), 828 - 32
A new antiherpetic agent, AH-1763 IIa, produced by Streptomyces cyaneus strain no . 1763; Uyeda M et al.; A new antiherpetic agent, AH-1763 IIa, was isolated from the culture broth of strain No . 1763 identified as Streptomyces cyaneus . It was purified through column chromatographies of Diaion HP-10 and silica gel . The structure was determined to be 11-hydroxy-5-methyl-2-(2-hydroxy-1-methylpropyl)-4H-anthraceno {1,2-b}pyran-4,7,12-trione by several spectroscopic experiments, that is a new antibiotic belonging to pluramycin-group.

Acta Paediatr, 1997 Nov, 86(11), 1195 - 7
Usefulness of chest physiotherapy with positive expiratory pressure (PEP)-mask in HIV-infected children with recurrent pulmonary infections; Plebani A et al.; Eight children with human immunodeficiency virus (HIV) and recurrent bacterial pulmonary infections were treated using a Positive Expiratory Pressure (PEP)-mask twice a day for 12 months . At the end of the study, a reduction in the number of pulmonary infections {mean (SD) 2.1 (0.9) vs 4.5 (1) p < 0.0001} and antibiotic courses {mean (SD) 1.5 (0.7) vs 2.4 (0.9) p < 0.021} was noted . The PEP-mask is a chest physiotherapy technique for removing infected secretions and optimizing airway functions that is also useful in HIV-infected children.

Am J Gastroenterol, 1997 Dec, 92(12), 2213 - 5
Randomized comparison of ranitidine bismuth citrate-based triple therapies for Helicobacter pylori; Laine L et al.; OBJECTIVES: In an attempt to increase the efficacy and simplicity of FDA-approved regimens for Helicobacter pylori, we studied (1) addition of an inexpensive antibiotic (amoxicillin) to twice-daily ranitidine bismuth citrate (RBC)-clarithromycin dual therapy, and (2) substitution of RBC for bismuth subsalicylate + H2-receptor antagonist in bismuth-based triple therapy . METHODS: Subjects with previously untreated Helicobacter pylori infection documented by 13C-urea breath test plus either endoscopic biopsy or serology were randomly assigned to a 2-wk course of (1) RBC 400 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d . (RAC), or (2) RBC 400 mg b.i.d., metronidazole 250 mg t.i.d., and tetracycline 500 mg t.i.d . (RMT) . Repeat breath test was performed 4 wk after the completion of therapy . RESULTS: Intent-to-treat and per-protocol cure rates for RAC were 46 of 50 patients (92%) and 45 of 47 patients (96%); for RMT they were 40 of 50 patients (80%) and 37 of 42 patients (88%) . Study drugs were stopped due to side effects in three patients (6%) taking RAC and six patients (12%) taking RMT . CONCLUSIONS: Twice-daily RBC-based triple therapy with clarithromycin and amoxicillin produces Helicobacter pylori eradication rates over 90%, which is comparable to rates seen with proton pump inhibitor-based triple therapies . RBC also may be substituted for bismuth subsalicylate and an + H2-receptor antagonist in standard bismuth-based triple therapy.

J Biomol Struct Dyn, 1997 Oct, 15(2), 277 - 84
An improved method for the rapid assessment of DNA bending by small molecules; Salzberg AA et al.; Assessing the effects of non-covalently bound chemicals on DNA structure is particularly challenging . Traditional methods require the use of cumbersome electrophoretic techniques or that the compounds bind DNA with an extremely high affinity . Here we demonstrate that, by extending the use of the exonuclease Bal 31, we can rely on a standard cyclization assay technique and one dimensional gel electrophoresis to identify and quantitate chemical induced DNA bending . An important application of this method is to the study of small molecules that bind to DNA non-covalently and we illustrate the method with the antitumor antibiotic calicheamicin . Our results suggest that the distribution of circles resulting from the polymerization of a 21 bp DNA construct reflects the kinetics of the competing cyclization and dimerization reactions and provides a method for rapidly screening compounds for DNA bending.

Mol Carcinog, 1997 Nov, 20(3), 308 - 16
Induction of mouse cytochrome P450 2B enzymes by amine metabolites of musk xylene: contribution of microsomal enzyme induction to the hepatocarcinogenicity of musk xylene; Lehman-McKeeman LD et al.; Musk xylene (MX) is a synthetic nitromusk perfume ingredient that, although uniformly negative in genotoxicity testing, causes liver tumors in B6C3F1 mice . MX is also capable of inducing cytochrome P450 enzymes in a manner similar to that of phenobarbital (PB), which suggests that epigenetic mechanisms may be involved in the carcinogenic response . At the same time, MX is metabolized in vivo by nitroreduction, a reaction catalyzed by intestinal flora that yields aromatic amine metabolites . These amine metabolites are also capable of inactivating CYP2B10, the major cytochrome P450 enzyme induced by MX treatment . In the study reported here, the monoamine metabolites of MX, o- and p-NH2-MX, were evaluated for their potential to induce CYP2B10 and CYP1A2 mRNAs . Northern blot analyses indicated that both amines markedly induced CYP2B10 mRNA, whereas CYP1A2 mRNA, the enzyme implicated in the bioactivation of aromatic amines and frequently induced by aromatic amines, was induced only slightly, a response that was not different from that seen with PB . Induction of CYP2B10 mRNA suggested that the amine metabolites may contribute to the enzyme induction profile seen with MX treatment . To test this hypothesis, mice were treated with broad-spectrum antibiotics (neomycin, tetracycline, and bacitracin) to eliminate the intestinal flora and prevent formation of o- and p-NH2-MX . In antibiotic-treated mice treated with MX (200 mg/kg) for 4 d, no evidence of microsomal enzyme induction was observed, including no increases in liver weight, total cytochrome P450 content, or CYP2B protein levels . These results indicate that the amine metabolites of MX are responsible for the enzyme induction seen after MX administration . Thus, the biochemical and molecular effects of amine metabolites of MX are markedly different from those of other aromatic amines but very similar to those of PB . Therefore, it appears that MX is a non-genotoxic chemical that may cause mouse liver tumors in a manner analogous to that of PB.

Kidney Blood Press Res, 1997, 20(4), 264 - 70
Advantages of a two-chamber culture system to test drug nephrotoxicity: the example of cephaloridine; Bolon C et al.; Rabbit renal proximal tubular cells, cultured to confluency on a permeable collagen film in a two-chamber system, were exposed for 72 h to various concentrations of the nephrotoxic antibiotic, cephaloridine (CLD) . A decrease in cellular proteins, leakage of lactate dehydrogenase and morphological changes appeared at CLD concentrations of 0.1, 1.0, and 0.5 mg/ml, respectively . The permeability of the monolayer to Lucifer yellow (LY), a dye that does not cross cell membranes, was increased by 1 or 2 mg/ml but not by lower concentrations of CLD . The large basolateral/apical glucose concentration gradient established by the cells was decreased by CLD . However, the fact that, at the CLD concentration of 1 mg/ml, LY totally equilibrated by diffusion across the monolayer, whereas the injured monolayer was still able to maintain a detectable glucose gradient, shows that damage caused by CLD to the diffusion barrier prevails over that affecting glucose uptake . Consistent with the data in the literature concerning the mechanism of CLD accumulation in renal cells, our results show that CLD was more toxic when it was added at the basolateral than at the apical side of the cultured cells . These results illustrate the advantages of using a two-chamber system of cell culture in nephrotoxicity studies.

Ostomy Wound Manage, 1996 Nov-Dec, 42(10A Suppl), 40S - 47S
Clinical evaluation: outcomes, benchmarking, introspection, and quality improvement; Ennis WJ et al.; Transforming the current event-driven reimbursement system into a quality powered marketplace will require clinical evaluation of how care is delivered . The managed care marketplace is evolving in three stages, from an event-driven, cost-avoidance model, to which the concepts of "value" and "quality" are added, with the final addition of a more "public health" focus . Clinical evaluation is a scientific process of outcomes assessment, clinical guidelines, and benchmarking . This process was applied to a hospital-based outpatient wound clinic, leading to a determination that the overall clinic Kaplan-Meier median time to healing could be improved . Two groups of patients were studied, 141 retrospectively from 1993 to 1994 and 57 prospectively in 1995 . While there was no significant difference in the percentage healed between the groups, a significant difference in the median times to healing was revealed, which was linked to antibiotic use . Even when antibiotics were used prophylactically, the median times for healing were elevated from those without infections . Introspection led to fewer patients receiving preventive antibiotics . The overall lower median time to healing curve in 1995 can be explained by this change in clinical practice . This quality improvement demonstrates the utility of the clinical evaluation process as the healthcare marketplace evolves.

Nippon Ganka Gakkai Zasshi, 1997 Nov, 101(11), 874 - 8
{The long-term cystic bleb appearance and safety after trabeculectomy with mitomycin C}; Mizoguchi T et al.; The clinical appearance of cystic blebs and the incidence of bleb infection were retrospectively evaluated in 215 trabeculectomies with mitomycin C . The incidence of cystic bleb formation in trabeculectomy was 79% (169/215) . The cumulative incidence of the cystic bleb survival when using the Kaplan-Meier method was 73% in the 50th month after surgery . The incidence of large cystic bleb survival was better than that of small and localized cystic blebs . There was statistically significant difference . The incidence of cystic bleb survival without Seidel phenomenon and bleb infection was 96% in the first year after surgery and 91% in the third year . Bleb infections occurred in two of 169 eyes (1.2%) . Bleb infection was successfully treated and there were no cases of endophthalmitis . The large cystic blebs had a higher incidence of bleb infection than the small ones . In one of 25 eyes treated with antibiotic eye drops after surgery, the Seidel test was positive and bleb infection occurred . The Seidel test was positive in 5 of 96 eyes in which antibiotic eye drops were not used and bleb infection occurred in one of these 5 eyes.

Bull Soc Belge Ophtalmol, 1996, 263, 115 - 21; discussion 122
Indocyanine green angiographic findings in multifocal choroidopathies; Giovannini A et al.; With high definition videoangiography (TOPCON IMAGEnet H1024) the Authors studied 41 patients affected by multifocal choroidopathies (MC) (68 eyes with ophthalmoscopic or indocyanine green angiographic evidences): 29 females and 12 males; age 21-51 years with a follow up of 6-29 months . In the light of the evidence provided by FA and ICG the Authors present a classification of MC in three stages: Stage 1 of subclinical choroidal activity (5 eyes): characterised by the presence of hypofluorescent or hyperfluorescent spots visible only in the late phases of ICGA; stage 2 of clinically evident choroidal activity (45 eyes): in FA the spots are hypofluorescent in the early phases and hyperfluorescent with a slight diffusion in the late phases, in ICGA either hypofluorescent spots or less frequently hyperfluorescent spots and choroidal permeability alterations can be observed; stage 3 or healed stage (18 eyes): in FA the spots are hyperfluorescent without late leakage, in ICGA hypofluorescence can be observed during all angiographic phases . In 5 patients in stage 1 of subclinical activity, a systemic steroid therapy induced the regression of the hypofluorescent sports in ICGA, in 2 cases the regression of hyperfluorescent spots in ICGA was observed after systemic antibiotic therapy . The authors underline that ICGA could be a particularly useful tool for an early diagnosis and clinical monitoring of MC.

Nippon Yakurigaku Zasshi, 1997 Oct, 110(4), 183 - 93
{Pharmacological approach to control American foulbrood of honeybees}; Hayama T; In this review, I will describe honeybee biology from my prospective as a veterinary pharmacologist and will provide a summary of my research project to search for effective drugs to control American foulbrood, a bacterial disease of honeybees . In conclusion, mirosamicin, a macrolide antibiotic, as a preventive and glutaral, an alkylating agent, as a disinfectant were the most promising drugs.

Can J Gastroenterol, 1997 Oct, 11(7), 589 - 96
Helicobacter pylori: from bench to bedside; Chiba N et al.; With the exponential increase in research in the field of Helicobacter pylori a paradigm shift has occurred . It is now recognized that H pylori is a chronic infection of the stomach causing inflammation . Some patients remain asymptomatic, while others may develop dyspepsia, duodenal or gastric ulcer, gastric cancer or a mucosa-associated lymphoid tissue lymphoma . However, the role of H pylori in contributing to nonulcer dyspepsia or nonsteroidal anti-inflammatory drug gastropathy remains controversial . An effective vaccine against H pylori is years away . Major interest has focused on the questions "who should be investigated and therefore treated" and "what is the latest gold standard for eradication of H pylori"? In Europe, guidelines have been developed to help the practitioner answer these important questions . Canadian guidelines will soon be available . For persons with known peptic ulcer disease there should be unequivocal acceptance that the good clinical practice of eradicating H pylori will result in substantial savings in health care expenses . The original 'classical triple therapy' (bismuth, metronidazole and tetracycline {BMT}) has now been surpassed by the combination of a proton pump inhibitor (PPI) plus two antibiotics (metronidazole plus clarithromycin; amoxicillin plus clarithromycin; or amoxicillin plus metronidazole), each given twice a day for one week . In Canada, the regimen of omeprazole plus one antibiotic (amoxicillin or clarithromycin) was approved recently but gives an eradication rate that is lower than the current target of 90% . According to the European (Maastricht) recommendations, if a single treatment attempt with PPI plus two antibiotics fails, PPI plus BMT is recommended.

Am J Gastroenterol, 1997 Dec, 92(12 Suppl), 12S - 17S
Optimizing therapy for inflammatory bowel disease; Robinson M; This review focuses on current developments in the major categories of therapy used in the management of inflammatory bowel disease (IBD) . Conventional corticosteroids, although a mainstay of the acute treatment of IBD for many years, have many drawbacks, including a variety of side effects--particularly with chronic use . Budesonide appears to be relatively safe and at least moderately effective in inducing remission in active distal ulcerative colitis (UC) and Crohn's disease . Aminosalicylates, both oral and topical, have proven useful in managing mild-to-moderate active UC and mild active Crohn's disease, as well as in maintaining remission . Data from recent trials suggest that higher doses of mesalamine are generally more efficacious than lower doses . In addition, a combination of oral and rectal formulations may succeed when one route, alone, is not successful . The immunomodulatory agents azathioprine, 6-mercaptopurine, and methotrexate have been shown to be effective in the treatment of IBD and are now widely accepted as valuable parts of the therapeutic armamentarium . Cyclosporine, although effective, is associated with many toxicities, and patients must be monitored closely in centers experienced with this agent . Clinical trials of IL-10, IL-11, and anti-TNFalpha have also shown promise . Antibiotics have been used empirically for many years in the treatment of IBD . Larger clinical trials are warranted to explore the potential efficacy of antibiotic therapy . This has been accomplished with metronidazole in Crohn's disease, and other antibiotic trials are underway at this time . The investigational agents acemannan, heparin, and transdermal nicotine have also shown variable degrees of promise as possible therapies for IBD . Despite the variety of agents available for the treatment of IBD, none is ideal or universally accepted . Ongoing research into the well-established therapeutic agents, as well as novel drugs with more precise targets, may contribute to the design of a more nearly optimal regimen for IBD in the not-too-distant future.

Alcohol Clin Exp Res, 1997 Nov, 21(8), 1367 - 73
Effect of treatment with paromomycin on endotoxemia in patients with alcoholic liver disease--a double-blind, placebo-controlled trial; Bode C et al.; The results of experimental and clinical studies support the hypothesis that gut-derived endotoxins might be of relevance for the development and course of alcoholic liver disease . The aim of this study was to test the effect of a nonabsorbable, broad-spectrum antibiotic on endotoxemia in patients with alcoholic liver disease . Fifty patients with alcoholic liver disease (27 with cirrhosis, 23 without cirrhosis) were randomly assigned to receive either paromomycin sulfate (3 x 1 g/day) or placebo in a double-blind fashion for at least 3 weeks, and if possible 4 weeks . Endotoxin concentration, liver function tests, and other laboratory parameters were determined in weekly intervals . Endotoxin concentration was also determined in 15 healthy controls . Groups receiving paromomycin or placebo were similar for clinical and biological items collected initially . Mean initial endotoxin concentrations were significantly elevated in both groups (mean +/- SEM; paromomycin, 16.7 +/- 5.3 pg/ml; placebo, 17.5 +/- 6.9 pg/ml; healthy controls, 2.3 +/- 0.4 pg/ml) . Although the mean endotoxin concentration was lower in the verum group after 1 week (paromomycin, 8.0 +/- 1.9 pg/ml; placebo, 14.6 +/- 3.5 pg/ml; p > 0.05), paromomycin treatment had no significant effect on endotoxin concentration or liver function tests during the 4-week period . The beneficial effect of paromomycin treatment on endotoxemia in cirrhotics reported in earlier studies could not be reproduced under the conditions of this trial in patients with alcoholic liver disease.

Dev Med Child Neurol, 1997 Nov, 39(11), 762 - 5
Neurobrucellosis in childhood: six new cases and a review of the literature; Omar FZ et al.; Neurobrucellosis accounts for <1% of cases of brucellosis in children . Six new cases of neurobrucellosis are presented and data from 39 previously published cases are analysed . The incidence is equal in males and females, and the source of infection is likely to be unpasteurised milk . Clinical presentation varies from severe meningoencephalitis or peripheral neuropathy/radiculopathy to behavioural disturbance . Diagnostic certainty requires isolation of the organism from the CSF, but as this is rarely possible serological diagnosis can be performed with the Coombs test on the CSF . Treatment requires combination antibiotic therapy and should continue for at least 8 weeks.

J Bacteriol, 1997 Dec, 179(23), 7559 - 72
Characterization of the acc operon from the nopaline-type Ti plasmid pTiC58, which encodes utilization of agrocinopines A and B and susceptibility to agrocin 84; Kim H et al.; The acc locus from the Ti plasmid pTiC58 confers utilization of and chemotaxis toward agrocinopines A and B (A+B), as well as susceptibility to a highly specific antiagrobacterial antibiotic, agrocin 84 . DNA sequence analyses revealed that acc is composed of eight open reading frames, accR and accA through accG . Previous work showed that accR encodes the repressor which regulates this locus, and accA codes for the periplasmic binding protein of the agrocinopine transport system (S . Beck Von Bodman, G . T . Hayman, and S . K . Farrand, Proc . Natl . Acad . Sci . USA 89:643-647, 1992; G . T . Hayman, S . Beck Von Bodman, H . Kim, P . Jiang, and S . K . Farrand, J . Bacteriol . 175:5575-5584, 1993) . The predicted proteins from accA through accE, as a group, have homology to proteins that belong to the ABC-type transport system superfamily . The predicted product of accF is related to UgpQ of Escherichia coli, which is a glycerophosphoryl diester phosphodiesterase, and also to agrocinopine synthase coded for by acs located on the T-DNA . The translated product of accG is related to myoinositol 1 (or 4) monophosphatases from various eucaryotes . Analyses of insertion mutations showed that accA through accE are required for transport of both agrocin 84 and agrocinopines A+B, while accF and accG are required for utilization of the opines as the sole source of carbon . Mutations in accF or accG did not abolish transport of agrocin 84, although we observed slower removal of the antibiotic from the medium by the accF mutant compared to the wild type . However, the insertion mutation in accF abolished detectable uptake of agrocinopines A+B . A mutation in accG had no effect on transport of the opines . The accF mutant was not susceptible to agrocin 84 although it took up the antibiotic . This finding suggests that agrocin 84 is activated by AccF after being transported into the bacterial cell.

Crit Care Nurs Q, 1997 Nov, 20(3), 36 - 43
Hospital-acquired pneumonia and its management; Yagan MB; Hospital-acquired pneumonia (HAP) is an important cause of morbidity and mortality in the United States . Classifying the patient's pneumonia by the presence or absence of risk factors helps determine what organisms need to be considered as etiologic agents so that empiric antibiotic therapy can be initiated while cultures are pending . Medical care personnel can also use preventive strategies to help decrease the incidence of nosocomial pneumonia . This article will discuss pathogenesis, diagnosis, management, and prevention of HAP.

Eur J Pediatr, 1997 Nov, 156(11), 856 - 7
Septic arthritis of the hip by Fusobacterium necrophorum after tonsillectomy: a form of Lemierre syndrome?
Beldman TF, Teunisse HA, Schouten TJ.
Lemierre syndrome used to be a complication of severe oropharyngeal infection with regional thrombophlebitis, septicaemia and septic metastatic infections caused by Fusobacterium necrophorum in the pre-antibiotic era . A case of septic arthritis of the hip caused by F . necrophorum as a complication of tonsillectomy is reported in a 9-year-old boy . Conclusion: Lemierre syndrome, usually seen after an oropharyngeal infection, can also complicate tonsillectomy.

Intern Med, 1997 Nov, 36(11), 810 - 4
Pyogenic clavicular osteomyelitis associated with disseminated intravascular coagulation and acute renal failure in a patient with non-insulin-dependent diabetes mellitus; Yoshioka K et al.; Pyogenic osteomyelitis is often accompanied by diabetes, but the disease in the clavicula has rarely been reported . We describe an unusual case of a 53-year-old man with poorly controlled non-insulin-dependent diabetes mellitus who presented with pyogenic clavicular osteomyelitis and developed DIC and acute renal failure . A 67Ga scintigram revealed an abnormal accumulation of the isotope in the right clavicula, where magnetic resonance imaging (MRI) showed inflammatory changes . This suggests that a 67Ga scintigram and MRI are of clinical value for the early diagnosis of the disease . Antibiotic chemotherapy with gamma-globulin and gebexate mesilate, and hemodialysis almost cured his serious condition.

J Acquir Immune Defic Syndr Hum Retrovirol, 1997 Nov 1, 16(3), 153 - 60
Regional differences in use of antiretroviral agents and primary prophylaxis in 3122 European HIV-infected patients . EuroSIDA Study Group; Lundgren JD et al.; Little is known about how widely HIV-related drugs are used outside controlled clinical trials . We therefore assessed factors associated with use of antiretroviral (ARV) therapy and primary prophylactic regimens to prevent HIV-associated opportunistic infections . Baseline data from a prospective study from May to August 1994, on 3122 consecutive HIV infected patients with a CD4 count <500 cells/microl, followed in 37 centers from 16 European countries, were analyzed . Two thousand and twenty patients (65%) were receiving at least 1 ARV drug at the time of the study . ARV therapy was more frequently used among patients from southern and central Europe as compared with patients from northern Europe, especially among patients with CD4 counts >200 cells/microl (73%, 57%, and 42%, respectively, p < 0.0001) . Of patients on ARV therapy, 34% received open-label combination therapy . This proportion was higher in central Europe compared with other regions (27%, 50%, and 31% for southern, central, and northern Europe, respectively, p < 0.0001) . Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) was used by 85% of patients with a CD4 count <200 cells/microl, without marked regional differences . In patients without esophageal candidiasis or other invasive fungal infections, antifungal drugs were far less frequently used in patients from southern and central Europe compared with patients from northern Europe (10%, 10%, and 25%, respectively, p < 0.0001) . Only 5% of patients with a CD4 count <100 cells/microl received rifabutine as primary prophylaxis against nontuberculous mycobacterioses . ARV and antifungal therapies are used differently in different parts of Europe, whereas primary PCP prophylaxis is uniformly administered to most at-risk patients . U.S . recommendations on the use of antimycobacterial prophylaxis have not been implemented in Europe.

J Trauma, 1997 Nov, 43(5), 793 - 8
Staged management of infected humeral nonunion; Chen CY et al.; Fourteen patients with infected humeral nonunion complicated by sinus discharge were treated with a staged protocol consisting of (1) radical debridement with local antibiotic beads implantation, and (2) external skeletal fixation with autologous bone grafting . In the first stage, a thorough debridement and sequestrectomy were done . Antibiotic beads were used to obliterate the bone defect, and the wound was then directly closed . In the second stage, the bead chains were replaced with autogenous cancellous bone graft . Unilateral Hoffman external skeletal fixators were applied simultaneously . The mean follow-up period was 73.6 months (range, 29 months to 9 years) . The length of time to achieve bony union ranged from 3.5 to 8 months (average, 4.3 months) . Hoffman pin complication was found in two cases, which were then shifted to plate internal fixation . All the infections were eradicated, and the wounds healed without further skin graft or flap coverage . All the fractures achieved bony union except for one in a patient who died . Most patients acquired satisfactory function of elbow motion after removal of external fixation and physical therapy . The method of two-stage management was effective for infected humeral nonunion . Not only was the infection eradicated and osseous union achieved, but also the limb function and joint motion were preserved.

J Long Term Eff Med Implants, 1998, 8(2), 117 - 32
Fibrin sealant in vascular surgery: a review; Shireman PK et al.; Fibrin sealant (FS) is a mixture of concentrated fibrinogen and thrombin that creates a fibrin matrix that is slowly degraded by the body's fibrinolytic system . FS is currently being used in the clinical arena for many applications . Perhaps the most relevant indication for vascular surgeons concentrates on FS's hemostatic properties . Current research in many centers is investigating FS's capability to incorporate drugs and cytokines into the fibrin matrix for slow release as a drug delivery system for future clinical use . This review will focus on three main uses of FS: as an anastomotic sealant, as an antibiotic coating, and as an agent for endothelialization of grafts.

Ann Surg, 1997 Nov, 226(5), 606 - 12
Cutaneous closure after cardiac operations: a controlled, randomized, prospective comparison of intradermal versus staple closures; Johnson RG et al.; OBJECTIVE: To determine the difference in wound complication and infection rates between suture and staple closure techniques applied to clean incisions in coronary bypass patients . BACKGROUND: The true incidence of postoperative wound complications, and their correlation with closure techniques, has been obscured by study designs incorporating small numbers, retrospective short follow-up, uncontrolled host factors, and narrowly defined complications . METHODS: Sternal and leg wounds were studied prospectively, each patient serving as his or her own control . Two hundred forty-two patients with sternal and saphenous vein harvest wounds had half of each wound closed with staples and the other half with intradermal sutures (484 sternal and 516 leg segments) . Wound complications were defined as drainage, erythema, separation, necrosis, seroma, or infection . Infections were identified in the subset having purulent drainage, antibiotic therapy, or debridement . Wounds were examined at discharge, at 1 week after discharge, and at 3 to 4 weeks after operation . Patient preferences for closure type were assessed 3 to 4 weeks after operation . RESULTS: Neither leg nor sternal wounds had a statistically significant difference in infection rate according to closure method (leg sutured = 9.3% vs . leg stapled = 8.9%; p = 0.99, and sternal sutured = 0.4% vs . sternal stapled = 2.5%; p = 0.128) . There was, however, a greater complication rate in stapled segments (leg stapled = 46.9% vs . leg sutured = 32.6%; p = 0.001, and sternal stapled = 14.9% vs . sternal sutured = 3.7%; p = 0.00005) . Sutures were favored over staples among patients who expressed a preference (sternal = 75.6%, leg = 74.6%) . CONCLUSIONS: With the host factors controlled by pairing staples and sutures in each patient, we demonstrated a similar incidence of infection but a significantly lower incidence of total wound complications with intradermal suture closure than with staple closure.

Leuk Lymphoma, 1997 Aug, 26(5-6), 527 - 37
Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma; Pinotti G et al.; The purpose of this paper is to report the clinical characteristics and treatment outcome following different therapeutic approaches in a large series of patients with primary low-grade MALT lymphoma of the stomach . A total of ninety-three patients (median age 63 years) were reviewed . The patients were treated by different modalities (local treatment alone, combined treatment, chemotherapy, antibiotics alone); seven patients refused any treatment . The antibiotic-treated group of patients was prospectively followed with regular endoscopic biopsies, and their responses were histologically evaluated . The 5-years projected overall survival is 82% (95% C.I.; 67%-91%) in the series as a whole . Second tumors were observed in 21.5% of the patients in this series (95% CI 14%v to 31%) . There was no apparent difference in overall survival and event-free survival between patients who received different treatments . In the antibiotic-treated group histologic regression of MALT lymphoma was documented in 67% of patients (95% CI 51% to 80%) . In conclusion the indolent nature of the disease justifies a conservative approach . The use of antibiotics as first-line therapy may avert or at least postpone the indication for surgical resection in the majority of patients.

Hear Res, 1997 Nov, 113(1-2), 117 - 32
Cochlear pathology induced by aminoglycoside ototoxicity during postnatal maturation in cats; Leake PA et al.; Cochlear pathology resulting from neonatal administration of the aminoglycoside antibiotic, neomycin sulfate, was studied in young kittens at 15-24 days postnatal . Hearing thresholds showed severe to profound hearing loss in all but one animal . Scanning electron microscopy demonstrated that initial hair cell degeneration occurred in the extreme base (hook region) of the cochlea and sequentially progressed to the basal, middle, then the apical coil of the cochlea . The first row of outer hair cells degenerated first, followed by row 2, then row 3; the last cells to degenerate in a given region were the inner hair cells . This pattern of hair cell degeneration is similar to that seen in adults with neomycin ototoxicity . In contrast, the spiral ganglion exhibited a different pattern of degeneration with initial cell loss occurring in the middle of the cochlea, about 40-60% from the base (approximately 2.8-8 kHz) . Thus, neuronal degeneration apparently is not secondary to sensory cell loss, but rather comprises an independent process in these neonatal animals . Taken together, the findings suggest that the spiral ganglion cell loss in the middle cochlear turn results from increased aminoglycoside sensitivity associated with an earlier initial onset of function in these neurons as compared to other cochlear regions.

Zhongguo Zhong Xi Yi Jie He Za Zhi, 1996 Jul, 16(7), 390 - 3
{Clinical and experimental studies of zhenkeling oral liquor on treatment infantile cough}; Shi YM et al.; One hundred and seventy children with cough were divied into two groups at random . 120 patient were treated with Zhenkeling oral liquor (ZKL group) . The other 50 children were given pectoral syrup (control group) . The results showed that the total effective rates of ZKL group and control group were 96.7% and 56.0% respectively, and the markedly effective rates were 80.8%, 18.0% respectively (P < 0.001) . Animal experiments indicated Zhenkeling has the effect of relieving cough, reducing sputum and ameliorating asthma; their antibiotic and anti-inflammatory effects were discovered too . The dosage of Zhenkeling was 100 times as clinical dose in acute toxicity test and the dosage was 32, 16, 8 times as clinical dose in long term toxicity test respectively . No adverse action was found in these experiments.

Microbiology, 1997 Nov, 143 ( Pt 11), 3573 - 9
Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus; Ives PR et al.; This paper reports a novel use of cluster analysis for the identification of intermediary metabolites that are produced at rates closely correlated with those of antibiotic biosynthesis . This information was used to devise culture feeds resulting in enhanced production of clavulanic acid, an antibiotic of current worldwide commercial interest . The feeding strategies apparently alleviated a rate-limiting supply of the C3 precursor of clavulanic acid . C3 limitation may be a consequence of unusual nitrogen and carbon metabolism in Streptomyces clavuligerus . This approach has potential as a generic method for influencing biosynthetic pathway fluxes using feeds without knowledge of the biosynthetic pathway.

Vet Surg, 1997 Nov-Dec, 26(6), 492 - 6
Laparoscopic adhesiolysis in a horse; Bleyaert HF et al.; OBJECTIVE: The purpose of this report was to describe the use of laparoscopy as a method of treatment for abdominal adhesions in the horse . CLINICAL REPORT: Unilateral ovariectomy for removal of a granulosa cell tumor was performed through a diagonal paramedian approach in a 14-year-old Arabian mare . Progressive incisional swelling and hemorrhage culminated in acute incisional dehiscence with herniation of ileum on the sixth postoperative day . Septic peritonitis that responded to parenteral antibiotic therapy was identified 7 days after hernia repair . Seven days later, the mare had signs of abdominal pain, and adhesions of small intestine to the paramedian incision were identified on rectal palpation . Transrectally assisted laparoscopic adhesiolysis was performed . No further complications occurred . CLINICAL RELEVANCE: Laparoscopic adhesiolysis may provide better observation of adhesions and reduced postoperative morbidity compared with laparotomy.

Mol Cells, 1997 Oct 31, 7(5), 674 - 81
Identification of a gene cluster of biosynthetic genes of rubradirin substructures in S . achromogenes var . rubradiris NRRL3061; Sohng JK et al.; Rubradirin, an ansamycin antibiotic has been purified from Streptomyces achromogenes var . rubradiris NRRL3061 . It consists of four distinct structural moieties, rubransarol, 3-amino-4-hydroxy-coumarin, dihydroxydipicolinic acid, and 2,6-dideoxynitrosugar (DNS) . Polymerase chain reaction (PCR) primers were designed based on consensus sequences of dTDP-D-glucose 4,6-dehydratase, one of enzymes involved in the biosynthesis of 2,6-dideoxysugar . A PCR product was obtained from S . achromogenes var . rubradiris . Hybridization of the PCR product to a cosmid library constructed from S . achromogenes genomic DNA has led to the identification of three unlinked regions of DNA . One of three kinds of cosmid clones contains homologues of dTDP-D-glucose 4,6-dehydratase, 3-amino-5-hydroxybenzoic acid (AHBA) synthase, and eryA genes . The size of the gene homologous to eryA is 30 kb, and the AHBA synthase gene homologue resides between the eryA homologous genes . A gene cluster of rubransarol and 2,6-dideoxynitrosugar is around 50 kb . Sequencing of the PCR product from the AHBA synthase gene homologue isolated from S . achromogenes revealed 85% amino acid sequence homology (73/86) with the AHBA synthase from a rifamycin-producer . dTDP-D-glucose 4,6-dehydratase gene homologue was subcloned from one of the isolated cosmid clones and sequenced . It showed 65% homology (43/66) with dTDP-D-glucose 4,6-dehydratase from a streptomycin-producer.

Ann Thorac Surg, 1997 Nov, 64(5), 1486 - 8
Partial mitral homograft for tricuspid valve repair; Ramsheyi A et al.; We report a case of partial replacement of the tricuspid valve by a mitral homograft in a young drug addict with right heart endocarditis . Operation was indicated because of sudden severe tricuspid regurgitation and persistence of vegetations despite appropriate antibiotic therapy . Partial tricuspid valve replacement was performed with a segment of mitral homograft reinforced by a semirigid prosthetic ring . At 30-month postoperative follow-up the patient was in excellent clinical condition with a satisfactory echocardiographic result.

Ann Thorac Surg, 1997 Nov, 64(5), 1270 - 8
Cardiac operations in solid-organ transplant recipients; Mitruka SN et al.; BACKGROUND: The success of solid organ transplantation has resulted in an increasing pool of patients that subsequently require cardiac surgical procedures, yet the perioperative management of these patients is not well documented . We report a single institutional experience with the management techniques used and the outcomes of the cardiac surgical procedures performed in solid organ transplant recipients with functioning allografts . METHODS: Sixty-four patients underwent 66 cardiac procedures broken down as follows: coronary artery bypass grafting, 30; single or combined valve replacement-repair, 24; combined coronary artery bypass grafting and valve repair, 3; aortic repair, 4; pericardiectomy, 3; transmyocardial laser revascularization, 1; and native cardiectomy, 1 . Patients consisted of 40 kidney, 16 liver, 5 heart, 2 lung, and 1 liver and kidney transplant recipients . The mean interval from the time of transplantation to the cardiac operation was 53 months (range, 1 day to 220 months) . Forty-six male and 18 female patients in New York Heart Association functional class III or IV had a mean age of 53 years (range, 19 to 77 years); 50% (32/64) were diabetic, and 97% (62/64) were hypertensive . Immunosuppressive therapy, cardiopulmonary bypass, and medical management were similar in all patients . RESULTS: There were two (3%) perioperative deaths, one of which was caused by an arrhythmia-induced cardiac arrest, and there were seven (11%) late deaths from non-cardiac-related causes . Major complications included 12 infections (19%), ten mediastinal reexplorations for the control of bleeding (16%), and nine others (15%) . Sixteen of the 64 (25%) transplant recipients had chronic renal failure (serum creatinine levels, > 3 mg/dL), including 13 of 40 (33%) kidney transplant patients . Acute renal failure developed postoperatively in 7 (54%) of these 13 patients; the grafts failed permanently in 3 (23%) . Three patients (5%), 2 kidney transplant recipients and 1 lung transplant recipient, experienced transient acute rejection . Fifty of the 55 surviving patients are alive and well (New York Heart Association functional class I or II) without recurrent cardiac disease at a mean follow-up period of 22 months . CONCLUSIONS: Although the short-term morbidity was significant, the low mortality and low incidence of permanent graft dysfunction indicate that solid organ transplant recipients can safely and effectively undergo subsequent cardiac surgical procedures.

Trans R Soc Trop Med Hyg, 1997 Jul-Aug, 91(4), 416 - 9
Screening pulmonary tuberculosis suspects in Malawi: testing different strategies; Harries AD et al.; Alternative strategies for screening tuberculosis (TB) suspects are needed in sub-saharan Africa . Ambulatory adult TB suspects who were seen in the chronic cough room of Queen Elizabeth Central Hospital, Blantyre, Malawi, were assessed with respect to appropriateness of referral . Appropriate referrals (patients with cough 3 weeks or longer, weight loss and no antibiotic response) were screened by 3 sputum specimens for microscopy and culture of Mycobacterium tuberculosis and chest radiography (CXR) . Hypothetical strategy A (screening by sputum smear examination followed by CXR in patients with negative sputum smears) was compared with strategy B (screening by CXR followed by sputum smear examination in patients with a CXR consistent with TB) in terms of diagnostic efficacy and cost . Of 1127 patients referred to the cough room, 402 (38%) were appropriate TB suspect referrals . Of these, 111 (28%) were sputum smear-positive, 213 (53%) were culture-positive, and 221 (55%) had smear and/or culture-positive evidence of TB . Routine CXR was consistent with pulmonary (P) TB in 230 patients (57%) . With strategy A, 243 (60%) patients were diagnosed as PTB, but 40 (25%) of those not diagnosed as PTB had positive mycobacterial cultures . With strategy B, 230 patients (57%) were diagnosed as PTB, but 53 (31%) of those not diagnosed as PTB had positive mycobacterial cultures, including 13 with smear-positive sputum . The cost per diagnosed case of PTB was US$ 4.63 with strategy A and US$ 5.44 with strategy B . Screening patients with good criteria of TB has high diagnostic sensitivity, but screening by CXR is less effective and more costly than screening by sputum smear microscopy.

Geriatrics, 1997 Nov, 52(11), 39 - 40, 42, 45-7
Rosacea: how to recognize and treat an age-related skin disease; Litt JZ; Rosacea is an age-related disorder of the central portion of the facial skin whose peak onset occurs in persons in their 40s and 50s . A chronic and progressive condition of flare-ups and remissions, rosacea can be disfiguring if left untreated . Rosacea can be characterized as having three stages . Target areas for all symptoms include the cheeks, nose, chin, or forehead . Rosacea resembles a number of other dermatologic conditions, particularly acne vulgaris . The combination of oral and topical antibiotic therapy usually brings about remission . The key is to recognize the early signs and clinical picture so that accurate diagnosis can be made and therapy and counseling instituted.

Arch Dis Child, 1997 Sep, 77(3), 227 - 30
Impact of HIV on mortality from acute lower respiratory tract infection in rural Zambia; Smyth A et al.; AIMS: To establish the prevalence and clinical correlates of HIV among children with acute lower respiratory tract infection . METHODS: Children admitted to a rural Zambian hospital were studied over an eight month period . The diagnosis of acute lower respiratory tract infection was made clinically, according to World Health Organisation (WHO) criteria . Clinicians, who were unaware of the children's HIV status, prescribed antibiotic and supportive treatment according to WHO guidelines . HIV status was established using the polymerase chain reaction (Amplicor HIV1, Roche) applied to dried blood spots . RESULTS: Acute lower respiratory tract infection was diagnosed in 132 children (median age 8 months, range 1 month to 4 years) . The WHO criteria for severe or very severe pneumonia were met by 96/132 patients (73%) and 21 patients (16%) died . HIV dried blood spot PCR was positive in 14 cases (11%), of whom four fulfilled the WHO clinical case definition for paediatric AIDS and five died . The group as a whole were malnourished, but the HIV positive children were more severely malnourished (mean z score for weight = -3.01) than the HIV negative children (mean z score = -1.73, p < 0.001) . The relative risk of death was 2.6 in the HIV positive group but this was not significant (p = 0.079) . CONCLUSIONS: An important minority of children with acute lower respiratory tract infection in rural Zambia will be infected with HIV . However, most HIV positive children presenting with respiratory infection will survive given simple antibiotic and supportive treatment.

Biochim Biophys Acta, 1997 Sep 4, 1348(1-2), 63 - 9
Choline kinase from yeast; Yamashita S et al.; Choline kinase, the initial enzyme of the CDP-choline pathway, mediates the conversion of choline to phosphorylcholine and is localized in the supernatant fraction of cells . The enzyme also catalyzes the phosphorylation of ethanolamine, functioning as the initial enzyme of the CDP-ethanolamine pathway as well . Yeast choline kinase is encoded by a single structural gene, CKI, which was cloned by the genetic complementation of the choline kinase mutation cki . The deduced sequence comprises 582 amino acid residues with a molecular mass of 66316 Da and bears local sequence similarity to various protein kinases and bacterial antibiotic phosphotransferases . The expression of yeast choline kinase is transcriptionally repressed by myo-inositol and choline in a coordinate manner with other phospholipid-synthesizing enzymes in yeast.

Am J Obstet Gynecol, 1997 Oct, 177(4), 786 - 92
A randomized, prospective study comparing once-daily gentamicin versus thrice-daily gentamicin in the treatment of puerperal infection; Mitra AG et al.; OBJECTIVE: The efficacy, safety, and antibiotic-related charges for once-daily gentamicin with twice-daily clindamycin were compared with those of thrice-daily dosing of these antibiotics . STUDY DESIGN: Patients with puerperal endometritis or with chorioamnionitis in labor assessed to be at risk for endometritis were randomized to receive gentamicin 4 mg/kg intravenously every 24 hours with clindamycin 1200 mg intravenously every 12 hours (experimental arm) or gentamicin 1.33 mg/kg intravenously and clindamycin 800 mg intravenously every 8 hours (conventional dosing interval arm) . Primary outcomes included cure rates, mean length of treatment, antibiotic-related charges, and nephrotoxicity . Multiple logistic regression analysis was used to control for confounding variables . RESULTS: There were 135 and 137 patients randomized to the experimental and conventional interval arms, respectively . Cures were obtained in 94.1% and 87.6% of patients in the experimental and conventional arms, respectively (p = 0.06) . The experimental arm had mean antibiotic charges of $250.79 versus $442.49 in the conventional arm (p < 0.0001) . There was no permanent nephrotoxicity in either group . CONCLUSIONS: Once-daily gentamicin dosing with twice-daily clindamycin dosing is as efficacious and safe as the thrice-daily dosing of gentamicin and clindamycin for peripartum uterine infection . The experimental regimen results in substantial cost savings . The incidence of nephrotoxicity is low.

Crit Care Med, 1997 Nov, 25(11), 1789 - 95
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients; Muckart DJ et al.; OBJECTIVES: To determine the frequency of the proposed definitions for the systemic inflammatory response syndrome (SIRS), sepsis and septic shock, and to further define severe SIRS and sterile shock as determined at 24 hrs of admission to an intensive care unit (ICU) in critically ill trauma patients without head injury, and their relationships to mechanism of injury, Acute Physiology and Chronic Health Evaluation (APACHE) II score, risk of death, Injury Severity Score (ISS), number of organ failures, and mortality rate . DESIGN: Prospective, inception cohort analysis . SETTING: Sixteen-bed surgical ICU in a teaching hospital . PATIENTS: Four hundred fifty critically injured patients without associated head trauma . Penetrating trauma accounted for 70% (gunshot 202; stab 113) and nonpenetrating trauma for 30% (motor vehicle collision 103; blunt 32) of admissions . Three hundred ninety-four (88%) patients underwent surgical procedures . INTERVENTIONS: None . MEASUREMENTS AND MAIN RESULTS: Infective and noninfective insults were distinguished by the need for therapeutic or prophylactic antibiotics, respectively, based on an established antibiotic policy . Three hundred ninety-five (87.8%) patients fulfilled a definition of the SIRS criteria . The frequency of the definitive categories was SIRS 21.8%, sepsis 14.4%, severe SIRS 8.4%, severe sepsis 13.6%, sterile shock 9.3%, and septic shock 20.2% . Patients with penetrating trauma had a significantly higher frequency of sepsis, severe sepsis, and septic shock (p < .01) . The APACHE II score, risk of death, and number of organ failures increased significantly in both infective and noninfective groups with increasing severity of the inflammatory response . Sterile shock was associated with a significantly higher APACHE II score (p < .02), risk of death (p < .01), and number of organ failures (p = .03) compared with septic shock . Only sterile shock was associated with a significantly higher ISS (p < .01) . Organ system failure was significantly (p < .001) higher in nonsurvivors compared with survivors in all categories . The only significant (p < .001) difference in mortality rate was found between patients in shock and all other categories . CONCLUSIONS: The current definitions of SIRS, sepsis, and related disorders in critically injured patients without head trauma show a significant association with physiologic deterioration and increasing organ dysfunction . The only significant association with mortality, however, is the presence of shock . The definitions require refinement, with the possible inclusion of more objective gradations of organ system failure, if they are to be used for stratifying severity of illness in seriously injured patients.

BMJ, 1997 Oct 25, 315(7115), 1060 - 4
Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden; Nicholson KG et al.; OBJECTIVE: To evaluate the disease burden of upper respiratory infections in elderly people living at home . DESIGN: Prospective surveillance of elderly people . INTERVENTION: None . SETTING: Leicestershire, England SUBJECTS: 533 subjects 60 to 90 years of age . MAIN OUTCOME MEASURES: Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death . RESULTS: 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each . Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable . Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001) . The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections . Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus . CONCLUSIONS: Respiratory viruses cause substantial morbidity in elderly people . Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall . The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.

Lasers Surg Med, 1997, 21(5), 413 - 6
Progressive ascending telangiectasia treated with the 585 nm flashlamp-pumped pulsed dye laser; Perez B et al.; BACKGROUND AND OBJECTIVE: Progressive ascending telangiectasia (PAT) is a distinct entity with telangiectatic superficial vessels on lower extremities as its main clinical feature . A relationship with occult infections and response to antibiotic and antifungal drugs have been described, although not all cases can be successfully managed with these therapies . Our objective was to treat a woman with PAT that had failed to respond to systemic antibiotic and antifungal drugs . STUDY DESIGN/PATIENTS AND METHODS: A 44-year-old woman with PAT was treated with the flashlamp-pumped pulsed dye laser at 585 nm, with fluences varying from 7 to 7.25 J/cm2 . RESULTS: A successful outcome was obtained with this treatment approach, with no relevant adverse effects except for mild pigmentary changes . CONCLUSIONS: Although ectatic vessels on lower extremities are often resistant to dye laser therapy, superficial thin capillaries like those featuring PAT can be eliminated with the pulsed dye laser at 585 nm . Transient pigmentary changes occur on treated areas but they are expected to disappear in 6 to 12 months after treatment . Laser treatment should be considered in PAT despite the extension and location of the lesions.

Mt Sinai J Med, 1997 Nov, 64(6), 386 - 91
Extended-interval dosing of aminoglycosides; Blam ME et al.; Aminoglycosides are efficacious agents . Their use has declined partly because of the development of newer, presumably less toxic agents . Research shows that aminoglycosides can be dosed differently than in the past, maintaining efficacy while reducing aminoglycoside toxicities . Aminoglycosides administered with newer agents may help overcome antibiotic bacterial resistance and thus yield safe and more effective therapy . This study focused on the efficacy and safety of the aminoglycosides extended-interval dosing regimen and was conducted by a search of the literature . Data from The Mount Sinai Hospital regarding bacterial resistance patterns were collected . A nomogram describing the administration of the extended-interval dosing regimen is provided . Extended-interval dosing of aminoglycosides is as efficacious as administering these agents every 8 hours and may result in lower rates of toxicities . Extended-interval dosing also may cost less and be easier to administer . Aminoglycosides are less susceptible to bacterial resistance than many of the newer, currently favored antibiotics . Increasing the usage of aminoglycosides is likely to be safe and beneficial in the treatment of certain bacterial infections.

N Z Med J, 1997 Sep 26, 110(1052), 349 - 52
An audit of the assessment and management of adults admitted to Christchurch Hospital with community acquired pneumonia; Meyer RJ et al.; AIMS: To audit the management of adult patients admitted with community acquired pneumonia including the standards of clinical assessment, use of modified British Thoracic Society prognostic criteria and antibiotic therapy . METHODS: A prospective, 16 week, study of consecutive patients admitted to Christchurch Hospital with community acquired pneumonia . RESULTS: Ninety-six patients met the inclusion criteria . The median age was 70 years . A pathogen was identified in 28 (26%) patients . Forty two patients fulfilled the modified British Thoracic Society criteria for severe disease and all 9 deaths occurred in that subgroup . The management guidelines were followed without exception in only 15% of cases . Documentation of the prognostic criteria was often incomplete and therefore only 33% of those patients with severe disease were correctly identified . Seventy one percent of those with severe disease were treated with only one antibiotic and there was significant delay in administering the first dose in 44% of cases . A follow up chest radiograph was performed in 43 (51%) of those discharged . CONCLUSIONS: There was poor compliance with the management guidelines . There was a lack of awareness of the severity criteria leading to inadequate treatment in many cases . Further educational initiatives are indicated.

Eur Neurol, 1997, 38(3), 155 - 66
Acute and critical care in neurology; Bertram M et al.; The diagnostic and therapeutic management of selected neurological diseases requiring intensive treatment is summarized with special regard for current standards and new developments in therapy . Ischemic stroke is an emergency since the outcome can be improved by immediate and adequate general supporting as well as specific (thrombolytic) therapy in specialized stroke units . Surgical evacuation of supratentorial intracerebral hemorrhage is still controversial . We give an overview of conditions in which surgical therapy such as cerebellar hemorrhage and large, nondominant ganglionic hemorrhage might be advisable . Cerebral venous thrombosis is treated with full-dose intravenous heparin even if hemorrhage is present . In acute bacterial meningitis, early treatment of foci and empiric antibiotic therapy is crucial in order to prevent complications . The outcome of herpes simplex encephalitis can be favorably influenced by treatment with aciclovir and aggressive therapy of elevated ICP and seizures . Acute Guillain-Barre syndrome requires daily monitoring of vital functions in order to recognize the need for intensive care; intravenous immunoglobulins and plasmapheresis are equally recommended for clinical and financial reasons.

Curr Opin Pulm Med, 1996 May, 2(3), 198 - 205
Diagnosis and management of thoracic empyemas; Heffner JE; Parapneumonic effusions are frequent complications of bacterial pneumonia . Depending on the severity of the underlying pneumonia, the promptness of antibiotic therapy, and the virulence of the infecting organism, 5% to 50% of patients will require pleural fluid drainage to prevent progression to an empyema . The decision to drain the pleural space depends on multiple clinical, laboratory, and radiographic factors . Delayed drainage results in pleural loculations, prolonged hospitalizations, and increased mortality . Image-guided percutaneous chest catheters provided an effective method for draining both free-flowing and loculated effusions . Fibrinolytic agents are gaining wider acceptance for promoting drainage of loculated, viscous pleural fluid although randomized studies do not exist . Patients failing a chest tube drainage method should undergo early evaluation for an open surgical procedure.

Curr Opin Pulm Med, 1996 May, 2(3), 192 - 7
Pneumonia in the elderly; Marrie TJ; The incidence of pneumonia for elderly persons living in the community is 14 cases/1000 persons/y, whereas 33/1000 nursing home residents require hospitalization for pneumonia each year . Premorbid health status is more important than age in determining outcome from pneumonia in this age group . Two studies of mortality in the 2 years following pneumonia gave conflicting results . One study showed that the mortality rate was twice that which was expected . Both the clinical and radiographic diagnosis of pneumonia may be difficult in the elderly especially if there is co-existing congestive heart failure . Aspiration is an under-diagnosed cause of pneumonia in the elderly . Data from three randomized clinical trials indicate that intravenous antibiotic therapy can be changed to oral therapy when the patient has been afebrile (< 37.5 degrees C) for 16 hours, can take antibiotics by mouth, and has a leukocyte count returning towards normal . Adjunctive therapy with nutritional supplements and vitamin C may improve outcome in this group of patients . Yearly immunization with influenza A and B virus vaccine will reduce both the incidence of pneumonia and the rate of hospitalization for this infection . A discussion of pneumonia in the elderly is often divided into community-acquired pneumonia, which is treated at home or in a nursing home, or community-acquired pneumonia requiring hospitalization and nosocomial pneumonia . The latter is not described in this review.

Curr Opin Pulm Med, 1996 Mar, 2(2), 141 - 7
Management of chronic obstructive pulmonary disease; Navin DM et al.; Chronic obstructive pulmonary disease is the fourth leading cause of death in the United States, affecting approximately 10% of all adults . Several articles published during the past year contributed significantly to our understanding of the complicated management of this disease . New information concerning bronchodilators, antibiotic therapy, mechanical ventilation, pulmonary rehabilitation, nutrition, and lung transplantation will help physicians further refine the care delivered to these patients.

Curr Opin Pulm Med, 1995 May, 1(3), 202 - 8
Pulmonary infections in immunosuppressed patients; White DA et al.; Pulmonary infections continue to be a significant problem in patients immunosuppressed by cancer or by drugs given for malignancy, or rheumatologic or dermatologic problems . For the neutropenic patient, single-drug rather than combination antibiotic therapy is being increasingly used . The role of growth factors is also being defined . The availability of the new azoles and of alternative forms of amphotericin B have increased treatment options, particularly for invasive pulmonary aspergillosis . Pneumocystis carinii pneumonia continues to be a problem in this population, and controversy remains about the mode of transmission and the mechanism of disease caused by this infection . Exogenous infection rather than reactivation may play a small role . Appreciation of the role of community and opportunistic viruses in causing respiratory infection or other complications in the immunosuppressed population is also being further detailed.

J Acquir Immune Defic Syndr Hum Retrovirol, 1997 Sep 1, 16(1), 15 - 21
Cost-utility analysis of prophylactic treatment with oral ganciclovir for cytomegalovirus retinitis; Moore RD et al.; OBJECTIVE: Cytomegalovirus (CMV) retinitis is a relatively common opportunistic infection in late-stage HIV disease, causing significant morbidity and mortality . Prophylactic use of oral ganciclovir has recently been shown to decrease the incidence of CMV retinitis but is relatively expensive and may not be very well tolerated by many patients . We performed a decision analysis to assess the cost-effectiveness of prophylactic oral ganciclovir therapy . METHODS: A decision analysis using a Markov approach compared absence of prophylaxis and prophylaxis with oral ganciclovir . Estimates of effectiveness of prophylaxis and costs of illness were obtained from published literature . Drug costs were based on national average wholesale prices . All health care costs were based on 1996 U.S . dollars . Sensitivity analyses were done over ranges of estimates of cost and effectiveness . RESULTS: Using our baseline estimates of cost and effectiveness, use of oral ganciclovir prophylaxis in patients with CD4 counts <50 cells/mm3 would be associated with average lifetime health care costs of $104,746, compared with $90,985 for no prophylaxis . Using oral ganciclovir, the average quality-adjusted life-years (QALYs) would be 2.05, and the CMV retinitis-free life-years would be 1.64, compared with 1.87 and 1.27, respectively, for no prophylaxis . The incremental cost-utility of oral ganciclovir is $76,676 per year of life saved and $37,542 per year of additional CMV retinitis-free life . Oral ganciclovir would become more cost-effective relative to no prophylaxis if the probability of CMV retinitis while taking oral ganciclovir declined . Oral ganciclovir would be less cost-effective if the cost of treating CMV retinitis declines, if our estimates of quality of life are low, or if the overall incidence of CMV retinitis declines . CONCLUSIONS: Oral ganciclovir is a less cost-effective approach than several other interventions used for HIV-disease prophylaxis . It would potentially become cost-effective if it is possible to target oral ganciclovir prophylaxis to patients who are most likely to benefit.

J Antibiot (Tokyo), 1997 Sep, 50(9), 738 - 41
Thiocoraline, a novel depsipeptide with antitumor activity produced by a marine Micromonospora . II . Physico-chemical properties and structure determination; Perez Baz J et al.; Thiocoraline (1) is a new antitumor antibiotic isolated from the mycelium of Micromonospora sp . L-13-ACM2-092 . Its structure was elucidated to be a novel cyclic thiodepsipeptide on the basis of spectroscopic methods.

Nippon Rinsho, 1997 Oct, 55(10), 2687 - 92
{Comparative features of pneumonia associated with influenza}; Nagatake T; Three manifestations of pneumonia that are associated with influenza are well recognized: primary influenza viral pneumonia, secondary bacterial pneumonia and mixed viral and bacterial pneumonias . In an outbreak of influenza, primary influenza viral pneumonia has occurred predominantly . After a typical onset of influenza, there is a rapid progression of fever, cough and dyspnea . Physical examination and chest roentgenography reveal bilateral findings but no consolidation . A Gram stain of the sputum fails to reveal significant bacteria, and bacterial culture yield sparse growth of normal flora, where as viral cultures yield high titers of influenza virus . Such patients do not respond to antibiotics . Secondary bacterial pneumonia often produces a syndrome that is clinically distinguishable from that of primary viral pneumonia . Recrudescence of fever is associated with symptoms and signs of bacterial pneumonia such as cough, sputum production, and an area of consolidation detected on physical examination and chest roentgenography . Gram staining and the culture of sputum reveals a predominance of a bacterial pathogen, most often H . influenzae, S . pneumoniae, B . catarrhalis, or S . aureus . Such patients usually respond to specific antibiotic therapy . During an outbreak of influenza many cases an observed that do not clearly fit into either of the aforementioned categories . The disease is not relentlessly progressive, and yet the fever pattern may not be biphasic . These patients may have primary viral, secondary bacterial, or mixed viral and bacterial infection of the lung.

J Nurse Midwifery, 1997 Sep-Oct, 42(5), 403 - 8
Clinical bulletin No . 2-January 1997 . Early-onset group B strep infection in newborns prevention and prophylaxis; Ex-vivo whole blood cultures for predicting cytokine-release syndrome: dependence on target antigen and antibody isotype; University of Cambridge Neurology unit, Addenbrooke's Hospital, UK . mgw1001@medschl.cam.ac.uk

Ex-vivo whole blood assays have been evaluated for their ability to accurately predict the risk of a first-dose cytokine reaction developing in vivo following therapeutic antibody infusion . Tumour necrosis factor alpha (TNF alpha) release was rapidly detected in cultures incubated with either anti-CD52 antibodies of the human IgG1 or rat IgG2b isotype, and to a lesser extent with a human IgG4 isotype . Endotoxin contamination of the antibodies was not responsive for cytokine release, since polymixin B failed to inhibit cytokine release using concentrations of this antibiotic which neutralized the enhanced cytokine release seen from LPS-spiked antibody . A rat IgG2b antibody to CD45 and a human IgG1 anti-CD3 also induced significant TNF release, however, an aglycosyl anti-CD3 mutant devoid of adverse side-effects in vivo, did not result in cytokine release in vitro . Since the pattern of cytokine release seen following the clinical use of these antibodies was in good agreement with the findings of the ex-vivo whole cultures, this demonstrates the usefulness of this assay to predict cytokine release in vivo.

Gene, 1997 Oct 15, 199(1-2), 71 - 6
pRIBOTEX expression vector: a pTEX derivative for a rapid selection of Trypanosoma cruzi transfectants; Martinez-Calvillo S et al.; To improve the selection phenotype of the expression plasmid pTEX, a Trypanosoma cruzi rDNA (DNA coding for rRNA) gene spacer fragment (806 bp) containing a mapped transcription start point (tsp) was cloned in the vectors pTEX and pTEX-cat, generating the plasmids pRIBOTEX and pRIBOTEX-cat . T . cruzi cultures transiently transfected with pRIBOTEX-cat expressed a chloramphenicol (Cm) acetyltransferase (CAT) activity 16,000-fold greater than the activity observed with the parental vector pTEX-cat . Moreover, T . cruzi cells transformed with pRIBOTEX and pRIBOTEX-cat exhibited logarithmic growth in the presence of Geneticin (G418) 2 weeks earlier than that observed with controls transformed with pTEX . The plasmid copy number in stably transformed trypanosomes was about 50-times higher in cultures transformed with pTEX-cat than in cells transformed with pRIBOTEX or pRIBOTEX-cat . However, the neo RNA steady-state level and the CAT activity observed among the stably transfected cultures showed only modest differences . Finally, it was found that the pRIBOTEX vector was not episomally maintained as pTEX, but integrated into a chromosome indistinguishable from the one encoding rRNA . These features make pRIBOTEX a useful tool for transfection and rapid expression of genes in T . cruzi.

Am J Physiol, 1997 Oct, 273(4 Pt 1), C1298 - 305
Tunicamycin increases intracellular calcium levels in bovine aortic endothelial cells; Buckley BJ et al.; Tunicamycin is a nucleoside antibiotic that inhibits protein glycosylation and palmitoylation . The therapeutic use of tunicamycin is limited in animals because of its toxic effects, particularly in cerebral vasculature . Tunicamycin decreases palmitoylation of the endothelial isoform of nitric oxide synthase, stimulates nitric oxide synthesis, and increases the concentration of intracellular calcium ({Ca2+}i) in bovine aortic endothelial cells (B . J . Buckley and A . R . Whorton . FASEB J . 11: A110, 1997) . In the present study, we investigated the mechanism by which tunicamycin alters {Ca2+}i using the Ca2+-sensitive dye fura 2 . We found that tunicamycin increased {Ca2+}i without increasing levels of inositol phosphates . When cells were incubated in the absence of extracellular Ca2+, {Ca2+}i rapidly rose in response to tunicamycin, although a full response was not achieved . The pool of intracellular Ca2+ mobilized by tunicamycin overlapped with that mobilized by thapsigargin . Extracellular nickel blocked a full response to tunicamycin when cells were incubated in the presence of extracellular Ca2+ . The effects of tunicamycin on {Ca2+}i were partially reversed by washing out the drug, and the remainder of the response was inhibited by removing extracellular Ca2+ . These results indicate that tunicamycin mobilizes Ca2+ from intracellular stores in a manner independent of phospholipase C activation and increases the influx of Ca2+ across the plasma membrane.

Proc AMIA Annu Fall Symp . 1997;:56-60.
A clinical data repository enhances hospital infection control; Samore M et al.; We describe the benefits of a relational database of hospital clinical data (Clinical Data Repository; CDR) for an infection control program . The CDR consists of > 40 Sybase tables, and is directly accessible for ad hoc queries by members of the infection control unit who have been granted privileges for access by the Information Systems Department . The data elements and functional requirements most useful for surveillance of nosocomial infections, antibiotic use, and resistant organisms are characterized . Specific applications of the CDR are presented, including the use of automated definitions of nosocomial infection, graphical monitoring of resistant organisms with quality control limits, and prospective detection of inappropriate antibiotic use . Hospital surveillance and quality improvement activities are significantly benefited by the availability of a querable set of tables containing diverse clinical data.

Ann Allergy Asthma Immunol, 1997 Oct, 79(4), 333 - 8
Esophageal candidiasis as a complication of inhaled corticosteroids; Simon MR et al.; BACKGROUND: Oropharyngeal candidiasis is a well-described side effect of inhaled corticosteroids . Nevertheless, few cases of esophageal candidiasis have been reported . OBJECTIVE: To present a patient with esophageal candidiasis associated with inhaled corticosteroids . METHODS: Case report . RESULTS: Our patient is a 70-year-old white woman with a 20-year history of intrinsic asthma, well controlled on triamcinolone acetonide 400 micrograms, ipratropium bromide 36 micrograms, and pirbuterol acetate 400 micrograms, each inhaled four times daily . She reported no oral steroid use for > 4 years and that she always rinsed her mouth following triamcinolone acetonide inhalation . The patient had gastritis with peptic ulcer disease in the past and developed worsening dyspeptic pain and heartburn . Following discontinuation of cimetidine and initiation of ranitidine without improvement, esophagogastroduodenoscopy was performed . Several small white patches in the mid and distal esophagus could not be removed with pressure . A biopsy confirmed the diagnosis of candidal esophagitis . Following a 4-week course of fluconazole, the patient was clinically improved and follow-up esophagogastroduodenoscopy was normal . There was no evidence of underlying cellular immunosuppression, malignancy, or diabetes mellitus and no history of recent antibiotic usage . Delayed skin tests revealed 5 x 5 mm induration to dermatophytin . Delayed hypersensitivity to Candida and mumps tests was absent . There was strong in vitro lymphocyte transformation and a positive immediate skin test response to Candida . ELISA for human immunodeficiency virus was negative . T and B cell counts were normal with CD4 = 630/mm3, CD8 = 520/mm3, and absolute B cell = 120/mm3 . It is possible that this patient's immediate hypersensitivity response to Candida suppressed her delayed response . Candidal esophagitis is a rare, yet important, complication of inhaled corticosteroid use . CONCLUSION: Immunocompetent patients on inhaled corticosteroids with medically unresponsive symptoms of esophagitis should be investigated for esophageal candidiasis.

Hepatogastroenterology, 1997 Sep-Oct, 44(17), 1339 - 41
Prophylactic perioperative treatment in a patient with colon carcinoma complicated by polycythemia vera; Yamaguchi T et al.; A patient with colon carcinoma complicated by polycythemia vera (PV) who underwent a partial colectomy concomitant with prophylactic perioperative treatment resulting in successful outcome is herein described . Seven weeks after the cessation of the latest exacerbation of PV, a partial colectomy was performed . In order to prevent the development of disseminated intravascular coagulation and thrombotic complications, the following perioperative treatment was performed: administration of gabexate mesilate (2,000 mg/day), fresh frozen plasma (300 ml/day), heparin (5,000 IU/day) for 7 days and anti-thrombin-III for 4 days, and a potent antibiotic therapy for 12 days and graded elastic bandages around the bilateral lower extremities for 14 days . As a result, an uneventful postoperative course was achieved . The present case suggests that these treatments are useful in the perioperative management of PV patients.

Hepatogastroenterology, 1997 Sep-Oct, 44(17), 1276 - 80
Ceftriaxone in the treatment of spontaneous bacterial peritonitis: ascitic fluid polymorphonuclear count response and short-term prognosis; Mesquita MA et al.; BACKGROUND/AIMS: In this study, ascitic fluid polymorphonuclear (PMN) response, short-term prognosis, and factors related to hospital mortality were investigated in 62 cases of spontaneous bacterial peritonitis occurring in cirrhotic patients treated with Ceftriaxone (1g every 12 hours) . METHODOLOGY: The diagnostic criteria for (SBP) were ascitic fluid PMN count < 250 cells/mm3 and no evidence of secondary peritonitis . Analysis of ascitic fluid samples were obtained on admission, and on the 4th and 10th days of antibiotic therapy . RESULTS: The etiology of cirrhosis was alcohol in 63% of the cases, and 79.5% of patients belonged to Child-Pugh Class C . Ascitic fluid analysis showed positive cultures in 47% of the cases, and a marked decrease in PMN count during treatment (admission: 7762 +/- 2837; 4th day: 388 +/- 91; 10th day: 173 +/- 59 cells/mm3) . Ascitic PMN was < 250 cells/mm3 within 4 days of treatment in 33% of the cases . The hospital mortality rate was 24%, and was related to gastrointestinal hemorrhage, hepatic encephalopathy, renal failure and 4th day ascitic fluid PMN count . CONCLUSION: Ceftriaxone is a safe and effective option for the treatment of SBP.

Proc Natl Acad Sci U S A, 1997 Nov 11, 94(23), 12297 - 302
RNA-peptide fusions for the in vitro selection of peptides and proteins; Roberts RW et al.; Covalent fusions between an mRNA and the peptide or protein that it encodes can be generated by in vitro translation of synthetic mRNAs that carry puromycin, a peptidyl acceptor antibiotic, at their 3' end . The stable linkage between the informational (nucleic acid) and functional (peptide) domains of the resulting joint molecules allows a specific mRNA to be enriched from a complex mixture of mRNAs based on the properties of its encoded peptide . Fusions between a synthetic mRNA and its encoded myc epitope peptide have been enriched from a pool of random sequence mRNA-peptide fusions by immunoprecipitation . Covalent RNA-peptide fusions should provide an additional route to the in vitro selection and directed evolution of proteins.

J Mol Biol, 1997 Oct 31, 273(3), 586 - 99
Streptomycin binds to the decoding center of 16 S ribosomal RNA; Spickler C et al.; Streptomycin, an error-inducing aminoglycoside antibiotic, binds to a single site on the small ribosomal subunit of bacteria, but this site has not yet been defined precisely . Here, we demonstrate that streptomycin binds to E . coli 16 S rRNA in the absence of ribosomal proteins, and protects a set of bases in the decoding region against dimethyl sulfate attack . The binding studies were performed in a high ionic strength buffer containing 20 mM Mg2+ . The pattern of protection in the decoding region was similar to that observed when streptomycin binds to the 30 S subunit . However, streptomycin also protects the 915 region of 16 S rRNA within the 30 S subunit, whereas it did not protect the 915 region of the naked 16 S rRNA . The interaction of streptomycin with 16 S rRNA was further defined by using two fragments that correspond to the 3' minor domain of 16 S rRNA and to the decoding analog, a portion of this domain encompassing the decoding center . In the presence of streptomycin, the pattern of protection against dimethyl sulfate attack for the two fragments was similar to that seen with the full-length 16 S rRNA . This indicates that the 3' minor domain as well as the decoding analog contain the recognition signals for the binding of streptomycin . However, streptomycin could not bind to the decoding analog in the absence of Mg2+ . This contrasts with neomycin, another error-inducing aminoglycoside antibiotic, that binds to the decoding analog in the absence of Mg2+, but not at 20 mM Mg2+ . Our results suggest that both neomycin and streptomycin interact with the decoding center, but recognize alternative conformations of this region .

Aliment Pharmacol Ther, 1997 Oct, 11(5), 913 - 7
A United States multicentre trial of dual and proton pump inhibitor-based triple therapies for Helicobacter pylori; Laine L et al.; BACKGROUND: One-week proton pump inhibitor-based triple therapies are very popular in the US despite limited US data documenting efficacy . We assessed 1-week proton pump inhibitor triple therapies for Helicobacter pylori, and compared them to dual antibiotic therapies (to assess benefit of omeprazole) and to omeprazole-amoxycillin (to assess benefit of clarithromycin) in a large, randomized, US multicentre study . METHODS: Healthy subjects who were H . pylori-positive by rapid serological test and 13C-urea breath test were randomly assigned to (i) omeprazole (O) 20 mg b.d . + amoxycillin (A) 1 g t.d.s . for 14 days (OA); (ii) A 1 g b.d . + clarithromycin (C) 500 mg b.d . for 7 days (AC); (iii) C 250 mg b.d . + metronidazole (M) 500 mg b.d . for 7 days (CM); (iv) O 20 mg b.d . + C 250 mg b.d . + M 500 mg b.d . for 7 days (MOC); or (v) O 20 mg b.d . + C 500 mg b.d . + A 1 g b.d . for 7 days (OAC) . Repeat breath tests were done at 6 weeks to assess H . pylori status . RESULTS: Three hundred and two H . pylori-positive subjects at 25 centres received medication . Intention-to-treat cure rate was significantly higher for OAC (82%) than for MOC (67%), CM (59%), AC (18%) or OA (58%), Per-protocol cure rates were 85% for OAC and 75% for MOC . Discontinuation of therapy due to a side-effect occurred in 0-3% of each study group . CONCLUSIONS: One-week twice-daily triple therapy with omeprazole, amoxycillin and clarithromycin provides the best rate of eradication of the five regimens studied . However, treatment in the US for 7 days may be unable to achieve eradication rates of > or = 90% with proton pump inhibitor-based triple therapy.

Vojnosanit Pregl, 1997 Jul-Aug, 54(4 Suppl), 9 - 12
Maxillofacial war injuries during the war in former Yugoslavia; Jovic N et al.; War wounds of the maxillofacial region occur in 5-17% of casualties . In the Clinic for Maxillofacial Surgery of the Military Medical Academy, during the war in former Yugoslavia, 482 casualties with dominant wounds in the maxillofacial region were treated . The outcome of the treatment depended on the quality and speed of the first aid and general medical aid, as well as on qualified specialist treatment . Specificity of the management of the war wounds of maxillofacial region includes: minimal debridement of soft tissues, removal of only deperiosted fragments of bony tissues, valid reconstruction of bony and soft tissues defects, correct immobilization, antitetanus prophylaxis, adequate antibiotic therapy, as well as permanent and very meticulous postoperative care.

Eur J Ophthalmol, 1997 Jul-Sep, 7(3), 251 - 5
The significance of serum anti-Borrelia antibodies in the diagnostic work-up of uveitis; Mikkila H et al.; PURPOSE: To assess the utility of testing uveitis patients for anti-Borrelia antibodies in an area endemic for Lyme borreliosis . METHODS: We examined 161 uveitis patients for serum antibodies to Borrelia burgdorferi by Lyme ELISA . Antibodies were determined in patients with uveitis of unknown etiology and non-selectively from patients with an established diagnosis . RESULTS: Concentrations of antibodies to B . burgdorferi were elevated in 26 uveitis patients (16.1%), with elevated IgG in 11 of them (6.8%) . In four of these patients Lyme borreliosis was a highly suggestive cause of uveitis because of a history of tick bites, systemic symptoms, response to antibiotic therapy, and/or a positive polymerase chain reaction result . Other causes of uveitis were ruled out . All these patients had vitritis . CONCLUSIONS: Non-selective testing of uveitis patients for Lyme antibodies is not reasonable even in endemic areas . We recommend using the Borrelia antibody test only in cases of uveitis of unknown cause, especially in patients with vitritis or other symptoms of Lyme borreliosis.

Am J Surg Pathol, 1997 Nov, 21(11), 1307 - 15
Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma; Cerroni L et al.; Recently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group . The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions . We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs . For comparison, three patients with immunocytoma were included in the study . Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo . Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat . Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated . In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates . Reactive germinal centers were present in 75% of the cases . The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells . The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype . They expressed immunoglobulin G in the majority of the cases . Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern . A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases . Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains . Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens . Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results . Lesions were treated by surgical excision followed in some patients by local radiotherapy . Systemic antibiotic therapy was administered to three patients, with good response in two . The prognosis is excellent . After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma . Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.

Cell Mol Life Sci, 1997 Aug, 53(8), 667 - 72
Antimitotic effects of usnic acid on different biological systems; Cardarelli M et al.; Usnic acid is a biosynthesis product characteristic of several epiphytic lichens such as Evernia, Cladonia and Parmelia . Usnic acid has several interesting biological properties . It is an antibiotic and it also seems to exert an antimitotic action . It has even been postulated that usnic acid can play a role as an environmental indicator, since its concentration varies according to the presence of toxic agents . A series of tests have been run on different biological systems such as fungi, yeasts, plant cells and neoplastic human cell cultures in order to make a general evaluation of the properties of usnic acid and to highlight any analogy between its effects on phylogenetically distant organisms . The results obtained confirm some of the already known properties of usnic acid and identify concentration ranges that are active against cells from different organisms . Furthermore, at low concentrations, the acid displays a capacity to stimulate cell metabolism in some of the biological systems tested.

Arch Pediatr, 1997 Sep, 4(9), 832 - 8
{Evaluation of the ambulatory treatment of acute diarrhea in infants . Réseau interhospitalier d'evaluation des pratigues médicales dans les affections courantes de l'enfant}; Martinot A et al.; BACKGROUND: Gastroenteritis remains a common and expensive illness . Oral rehydration solutions (ORS) have been shown to be effective in the prevention and treatment of dehydration, the prime cause for diarrhea-related morbidity and mortality . OBJECTIVE: To evaluate the ambulatory management of acute gastroenteritis in infants, and particularly practices concerning oral fluid therapy . METHODS: This prospective, multicenter study included 326 infants (mean age: 10 +/- 6 months), examined in a hospital for acute gastroenteritis, with or without dehydration . RESULTS: Before admission, 81% had previously been examined by a practitioner, and 89% of these practitioners had written a prescription . This prescription included ORS in 35% and was not different according to the age of the infant . Pediatricians prescribed ORS more frequently than general practitioners (respectively 58% vs 29%; P < 0.001) . The failure rate of ORS prescription was 25% (two parents did not observe, ten children refused to drink, and eight stopped treatment because of vomiting) . Lactose-free milks were prescribed in 46% of infants and the observance was 82% . At least one drug was prescribed in 94% of infants, with a mean of 2.6 drugs per infant; one antibiotic was prescribed in 33% of infants . Infants were admitted to hospital without any previous consultation in 18%, on the parents' initiative but after at least one previous medical examination in 52%, and on the physician's initiative in 30% . Thirty-three percent were dehydrated; one infant died and two had sequellae . CONCLUSION: The use of ORS remains insufficient . Efforts to improve use of ORS should be expanded beyond physician education.

Presse Med, 1997 Sep 20, 26(27), 1284 - 8
{Risk of complications during endovesical treatment with BCG for superficial tumor of the bladder}; Allouc H et al.; OBJECTIVES: BCG therapy is the reference adjuvant treatment for multiple and voluminous or recurrent superficial bladder cancer and can cause specific complications . We assessed the frequency and therapeutic modalities involved associated with such complications in a personal retrospective series of patients . PATIENTS AND METHODS: BCG therapy was given to 148 patients who were followed for a mean 40 months . RESULTS: Forty-six percent of the patients developed a follicular reaction in the bladder wall: 14 developed complications requiring anti-tuberculosis treatment . The frequency of BCG therapy complications was higher in patients who had had tuberculosis previously (50%) than those who did not (13.8%) . Complications were more frequent after early treatment . In the patients who developed BCGitis with fever, a 3-month regimen of rifampicin and isoniazine appeared to be sufficient . DISCUSSION: The frequency of BCG therapy complications (bladder anomalies excluded) was 7.8% with only 2.8% major complications . The development of a follicular reaction of the bladder wall does not appear to have any prognostic value . Special surveillance is needed in patients with a past history of tuberculosis . CONCLUSION: Adjuvant BCG therapy requires careful follow-up because of the risk of BCGitis which can be effectively treated with a 3-month double-antibiotic regimen.

J Neurosurg, 1997 Nov, 87(5), 694 - 9
Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases; Chamberlain MC et al.; The authors studied complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases (LM) . One hundred twenty consecutive patients with LM (71 females and 49 males) ranging in age from 10 to 72 years (median 42 years) were treated with involved-field radiotherapy and intraventricular chemotherapy using an Ommaya reservoir and intraventricular catheter system . The diagnosis of LM was determined by a combination of clinical presentation (114 patients); cerebrospinal fluid cytological studies (100); or neuroradiographic studies (42) . Systemic tumor histological findings included breast (34 patients); non-Hodgkin's lymphoma (22); melanoma (16); primitive neuroectodermal tumors including medulloblastoma (10); glial neoplasms, leukemia, small cell lung, nonsmall cell lung, and colon (six each); prostate and kidney (three each); and gastric cancers (two) . Sixteen patients, all with non-Hodgkin's lymphoma, also had acquired immune deficiency syndrome . Patients received one to four (median two) chemotherapeutic drugs and underwent a total of 1110 cycles of intraventricular chemotherapy (median 10) . Intraventricular chemotherapy administration and diagnostic Ommaya reservoir punctures totaled 4400, with a median of 46 per patient . Complications included aseptic/chemical meningitis (52 patients); myelosuppression due to intraventricular chemotherapy (21); catheter-related infections (nine); unidirectional catheter obstruction (six); intraventricular catheter malpositioning (two); Ommaya reservoir exposure (two); leukoencephalopathy (two); and chemotherapy-related myelopathy (one) . There were no treatment-related deaths; however, seven patients (6%) required additional surgery for either catheter repositioning (two) or reservoir removal (five) . Seven patients with catheter-related infections were treated successfully with intraventricular and systemic antibiotic drugs, thereby preserving the Ommaya system . The authors conclude that Ommaya reservoirs are convenient and pharmacologically rational systems for administering intraventricular chemotherapy . Overall, serious complications requiring surgery are infrequent (6%) and most often secondary to catheter infections, Ommaya reservoir exposure, or initial catheter malpositioning . In the majority of instances, catheter infections may be managed medically, as may the most common complications of intraventricular chemotherapy including aseptic meningitis (43% of patients) and myelosuppression (18%).

Mikrobiol Z, 1997 May-Jun, 59(3), 33 - 41
Comparative characteristics of some cultural and toxigenic properties of the Dendrodochium Bonorden and Myrothecium Tode ex Fr . representatives; Zaichenko OM et al.; The comparative study of sporulation intensity, change of medium pH, yield of biomass and ethanol soluble fraction (ESF) of extracellular metabolites as well as antibiotic and toxigenic properties of 106 fungi strains which were the potential producers of macrocyclic trichothecenes has been carried out under the conditions of stationary cultivation . It was shown that all the studied Dendrodochium strains were characterized by moderate growth, variations of biomass were within 3.5-4.5 g/l . Variations of ESF level in different strains were rather essential (from 8 to 241.6 mg/l) . High antibiotic activity correlated with high or moderate toxicity (on the basis of rabbit skin test) in most cases . Dendrodochium strains with intensive sporulation were as a rule characterized by high efficiency of toxin production (40% of studied strains) and only 3 strains (5.5%) with low level of sporulation were characterized by high rate of toxin production . The toxigenic activity for Myrothecium cinctum, M . commune and M . ukrainicum has been shown for the first time . The toxigenic activity of the studied strains depending on the source of isolation and possible correlative connections between sporulation, toxin formation and other properties are discussed.

Liver Transpl Surg, 1997 Mar, 3(2), 149 - 52
Methemoglobinemia associated with dapsone treatment in solid organ transplant recipients: a two-case report and review; Plotkin JS et al.; Dapsone, a sulfone antibiotic, has been increasingly used in solid-organ transplant recipients for the primary prevention of Pneumocystis carinii pneumonia, especially in patients with documented sulfa allergy . A known side effect of dapsone therapy, however, is methemoglobinemia, a condition leading to impaired tissue oxygen delivery . This report documents two cases of dapsone-induced methemoglobinemia in patients after solid organ transplantation with emphasis on the importance of clinical recognition and benefits of treatment . Further, the pathophysiology and causes of this condition are extensively reviewed.

Biochem Biophys Res Commun, 1997 Oct 9, 239(1), 134 - 8
Actinomycin D amplifies site-specific DNA cleavage induced by neocarzinostatin; Hiraku Y et al.; Neocarzinostatin (NCS) is an antineoplastic antibiotic causing DNA cleavage . Actinomycin D (ActD) is an antineoplastic antibiotic, which does not cleave DNA strands . We examined the mechanism of ActD-mediated amplification of NCS-induced DNA cleavage using 32P-labeled DNA fragments obtained from the human c-Ha-ras-1 proto-oncogene . NCS plus glutathione caused DNA cleavage at thymine and adenine residues in the absence of ActD . The addition of ActD enhanced the DNA cleavage at the sites at which the lesions on opposite strands are staggered 2 bases in a 3' direction, particularly at the 5'TCT-3'.3'-AGA-5', 5'-TGT-3'.3'-ACA-5' and 5'-ACT-3'.3'-TGA-5' sequences, suggesting that ActD amplified double-stranded DNA cleavage . The mechanism of ActD-mediated amplification of NCS-induced DNA cleavage can be explained by assuming that binding of ActD to DNA changes the DNA conformation to allow NCS to bind to DNA at the specific sequences.

J Am Coll Surg, 1997 Oct, 185(4), 404 - 7
Does vaginal cuff closure decrease the infectious morbidity associated with abdominal hysterectomy?
Korn AP, Grullon K, Hessol N, Lin P, Siopak J.
BACKGROUND: Infectious morbidity after total abdominal hysterectomy includes fever (31%) and antibiotic administration (45%) . Whether vaginal cuff closure reduces postoperative infectious morbidity remains unresolved . STUDY DESIGN: We reviewed the records of 172 consecutive abdominal hysterectomies for nonmalignant disease performed at an inner-city hospital . We identified potential risk factors for infectious morbidity by univariate analysis and determined adjusted odds ratios by multiple logistic regression analysis . RESULTS: The open vaginal cuff technique was associated with an increased risk of wound infection . Use of prophylactic antibiotics was associated with a decreased risk of febrile morbidity and a decreased risk of prolonged hospitalization . Body weight in the heaviest quartile was associated with increased risk of wound infection, increased risk of prolonged hospitalization, and decreased risk of postoperative vaginal cuff granulation tissue . Older age was associated with an increased risk of prolonged hospitalization . CONCLUSIONS: Closure of the vaginal cuff and use of prophylactic antibiotics at total abdominal hysterectomy were associated with decreased infectious morbidity in a high-risk population.

Bioconjug Chem, 1997 Sep-Oct, 8(5), 617 - 20
Identification of preferred distamycin-DNA binding sites by the combinatorial method REPSA; Hardenbol P et al.; The combinatorial method restriction endonuclease protection, selection, and amplification (REPSA) was used to determine the preferred duplex DNA binding sites of the peptide N-methylpyrrolecarboxamide antibiotic distamycin A . After 12 rounds of REPSA, several sequences were identified that bound distamycin with an apparent affinity of 2-20 nM . Among these, the highest-affinity sites averaged 10 bp in length, suggesting that these sites may be occupied by multiple, cooperatively interacting distamycin molecules . Presently, REPSA is the only combinatorial approach that allows the identification of preferred DNA targets for small molecule ligands at physiologically relevant concentrations in solution . As such, it should prove useful in the design and screening of sequence-specific DNA-binding molecules.

Pharmacotherapy, 1997 Sep-Oct, 17(5), 938 - 58
Identification, diagnosis, and treatment of acid-related diseases in the elderly: implications for long-term care; Garnett WR et al.; Acid-related disorders such as peptic ulcer disease and gastroesophageal reflux disease occur frequently in the elderly and are associated with a high frequency of morbidity and mortality . The proton pump inhibitors lansoprazole and omeprazole produce faster rates of healing and greater symptomatic relief in patients with acid-related disorders than histamine2-receptor antagonists, are well tolerated, and are associated with few adverse events . Compared with omeprazole, which interacts with diazepam, warfarin, and phenytoin, lansoprazole produces only a minor increase in theophylline clearance . Proton pump inhibitors in combination with antibiotic therapy can eradicate Helicobacter pylori, the main risk factor in the recurrence of peptic ulcer disease, obviating the need for maintenance therapy . Long-term acid suppression with proton pump inhibitors may be necessary to prevent the recurrence of gastroesophageal reflux disease . The safety and efficacy profile of these agents makes them ideal for the treatment of acid-related diseases in elderly patients.

Zentralbl Veterinarmed B, 1997 Sep, 44(7), 415 - 24
The use of Baypamun N in crowding-associated infectious respiratory disease: efficacy of Baypamun N (freeze dried product) in 2-week-old veal calves; Ziebell KL et al.; The efficacy of an immunomodulator, Baypamun N, was tested in 10-20-day-old veal calves from different farms, which were exposed to stress by transport and commingling (crowding) . Verum and placebo animals (n = 50, each group) received three intramuscular injections of the investigational products (days 0, 2, 4) starting the day of arrival on the farm . Data from 49 calves in each group could be used for statistical evaluation . The incidence of acute bovine respiratory disease was anticipated to be high during the first 2 weeks after arrival on farm based on experience from other years . The clinical scores in the Baypamun N group were significantly reduced by 52.7% (P < 0.001) compared to the placebo group . The number of antibiotic treatments was significantly reduced by 53.8% (P < 0.001) in the Baypamun N group . Of the calves treated with Baypamun N, 51.02% remained untreated with antibiotics during the first 2 weeks after arrival on the farm compared with only 16.3% of the placebo treated control calves (P < 0.001).

Hear Res, 1997 Sep, 111(1-2), 177 - 84
Apoptosis and hair cell degeneration in the vestibular sensory epithelia of the guinea pig following a gentamicin insult; Lang H et al.; Apoptosis plays a key role in the steady state of continuously renewing tissues . The goal of this study was to determine whether apoptosis was a mode of hair cell loss in mammalian inner ear sensory epithelia . Hair cell loss was induced by systemic treatment with the ototoxic aminoglycoside antibiotic gentamicin in guinea pig . The vestibular sensory epithelia were examined at different times after administration via semi-thin and thin sections in situ labeling by the terminal deoxynucleotidyl transferase catalysis of digoxigenin tagged nucleotides to the free 3'-OH ends of fragmented DNA . Apoptotic labeling was detected 3-7 days after treatment . The majority of the apoptotic nuclei was found adjacent to the luminal surface . Analysis of semi-thin and thin sections revealed two modes of hair cell degeneration: (1) Apoptosis within the epithelium, showing typical morphological changes of condensation and fragmentation of the nucleus and modifications of cytoplasmic organelles . (2) Swelling of the cell, vacuolation and distortion of cell shape, and extrusion into the lumen . The results indicated that vestibular hair cells undergo apoptosis after ototoxic traumas.

Pediatr Infect Dis J, 1997 Sep, 16(9), 842 - 6
Effect of rapid viral diagnosis on the management of children hospitalized with lower respiratory tract infection; Adcock PM et al.; BACKGROUND: Although rapid viral tests are commonly used in children with lower respiratory tract infection, their effect on patient management has not been studied . OBJECTIVES: To examine how physicians utilize an enzyme immunoassay for respiratory syncytial virus (RSV EIA) and a centrifugation-enhanced cellular immunofluorescence assay for multiple viral pathogens {viral respiratory panel (VRP)} in children hospitalized with respiratory illness; to determine the effect of testing on length of stay, antibiotic use and costs; and to determine physician attitudes toward RSV testing . DESIGN AND SETTING: Prospective study and survey at a large children's hospital . PATIENTS: Previously healthy children < 24 months of age consecutively admitted between January 1 and February 11, 1995, with symptoms of lower respiratory tract infection . RESULTS: Of 200 patients 160 were tested by RSV EIA; 92 were positive and 68 were negative . Tested children were younger, more tachypneic and more likely to require oxygen than those not tested . Overall the length of stay was similar in RSV-positive and -negative patients . Although equal proportions of each group were given antibiotic therapy, RSV-positive children received antibiotic therapy for fewer days than RSV-negative children (median 2 vs . 3 days; P = 0.0387) . However, a crude cost analysis did not support a strategy of testing all bronchiolitis patients for RSV . Sixty-five of the 68 RSV-negative children were tested for RSV and other pathogens by VRP . In 55 cases the results were not available until after patient discharge and could not have influenced their management . One hundred three physicians caring for children in the study were surveyed . Of 75 respondents almost all thought that RSV EIA results influenced their management of patients and were important to parents . CONCLUSIONS: Most children hospitalized with symptoms of lower respiratory tract infection were tested for viral pathogens . The VRP provided little clinically useful information . In contrast RSV EIA results may have been used by clinicians to make antibiotic decisions . Physicians felt that rapid testing for RSV was important.

J Arthroplasty, 1997 Sep, 12(6), 709 - 10
New uses for gentamicin-impregnated polymethyl methacrylate spacers in two-stage revision hip arthroplasty; Oxborrow NJ et al.; The use of antibiotic-impregnated cement as a bone spacer in two-stage revision hip surgery has been well described . Two additional placements for spacers are described: within the trochanteric osteotomy and overlying the greater trochanter . These spacers have been found to dramatically facilitate exposure at the second-stage procedure and are now being incorporated into all two-stage revision hip arthroplasties at The General Infirmary at Leeds.

J Arthroplasty, 1997 Sep, 12(6), 615 - 23
The outcome of two-stage arthroplasty using a custom-made interval spacer to treat the infected hip; Younger AS et al.; Sixty-one patients undergoing a two-stage revision of an infected hip using a prosthesis of antibiotic-loaded acrylic cement were followed for an average of 43 months . Twelve patients were excluded (3 died, 6 had no proven infection, and 2 no second stage) . Only 1 patient was lost to follow-up evaluation from those included, for a retrieval rate of 98% for those still living . Of the remaining 48 patients, 3 had further sepsis: Two became reinfected with different organisms and 1 with the same organism, for an infection eradication rate of 94% . The other 45 had no clinical, laboratory, or radiographic evidence of infection . Thirty-seven patients (80%) had a Harris hip score greater than 80 or an improvement of at least 30 points.

Curr Med Res Opin, 1997, 13(10), 593 - 601
Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy . A double-blind, randomised trial; Miglio F et al.; The aim of this study was to evaluate the efficacy and tolerability of rifaximin, a non-absorbable intestinal antibiotic, in comparison to neomycin in the short- and long-term treatment of hepatic encephalopathy (HE) . Forty-nine patients with a definite diagnosis of cirrhosis were included in this double-blind, randomised, controlled trial . Patients were randomly assigned to one of the following treatments: (1) rifaximin 400 mg three times daily; (2) neomycin 1 g three times daily . Both drugs were administrated orally as tablets during 14 consecutive days each month, for a period of six months . The neuropsychiatric signs and blood ammonia levels were examined before starting the treatment, and every 30 days, until the final assessment . In all patients a progressive and important reduction in HE grade was observed, and no statistically significant difference between the two treatments was detected . In both groups the disturbances in speech, memory, behaviour and mood, gait, asterixis, writing, and serial subtraction of 7 s and five-pointed star tests all showed the highest proportion of improvement . During the study blood ammonia levels decreased in both the rifaximin and in the neomycin groups, and again no statistically significant difference was found between groups . Our findings confirm, therefore, the usefulness of rifaximin in the treatment of HE, supporting its use as a first-choice antibiotic, particularly in patients intolerant to neomycin or with impaired renal function.

Stem Cells, 1997, 15(5), 347 - 52
Evaluation of a cytokine combination including thrombopoietin for improved transduction of a retroviral gene into G-CSF-mobilized CD34+ human blood cells; Kim HJ et al.; We examined cell culture conditions with various combinations of cytokines including thrombopoietin (TPO) to obtain the most efficient transduction of recombinant retrovirus vectors into G-CSF-mobilized blood CD34+ cells which were obtained from children and purified with an Isolex 50 system (Baxter; Deerfield, IL) . Three different 4-day culture conditions for the stimulation of CD34+ cells were compared in terms of a cell-cycle analysis by fluorometry and gene transduction efficiency as determined by resistance to G418 and NeoR polymerase chain reaction (PCR) for individual colony-forming unit-granulocyte/macrophage (CFU-GM) grown in a methylcellulose culture system . The cytokines tested were: A) interleukin (IL)-6 + stem cell factor (SCF); B) IL-3 + IL-6 + SCF, and C) IL-3 + IL-6 + SCF + TPO . Without a cell culture, the percentage of CD34+ cells in the cell cycle (the percentage of cells in phases S and G2/M) was 4.6% . After a four-day culture (n = 5), this value increased with the addition of IL-3 (22%) or IL-3 + TPO (27%, p < 0.05) as compared to that with the baseline cocktail of IL-6 + SCF (15%) . The cell number uniformly increased approximately 10-fold in each culture condition . The average efficiency of gene transfer into incubated CD34+ cells with the corresponding combinations of cytokines was, respectively, 57%, 47%, and 30% for G418-screened CFU-GM and 72%, 68%, and 51% for polymerase chain reaction-positive CFU-GM . A statistically significant difference (p < 0.01) was found for G418/CFU-GM with IL-3 + IL-6 + SCF (57%) versus IL-3 + IL-6 + SCF + TPO (30%) . Hence, it is likely that the increased cell proliferation produced by the addition of TPO was not necessarily translated into an increased rate of retroviral-mediated gene transduction, possibly because TPO preferentially induced the differentiation of stem cells into mature progenitors in these culture systems.

Biotechniques, 1997 Oct, 23(4), 690 - 5
n beta geo, a combined selection and reporter gene for retroviral and transgenic studies; Blake J et al.; Nuclear-targeted beta-galactosidase (beta-gal) is increasingly used as a genetic cell marker in vitro and in vivo . Nuclear sequestration concentrates beta-gal and permits sensitive identification of expressing cells and/or tissues without obscuring the cytoplasmic detail necessary for analysis of cell phenotype . Here, we report the construction and testing of a nuclear-targeted version of the beta geo fusion protein that combines nuclear localization with the ability to select expressing cells with the drug G418 . This new marker gene functions efficiently in retroviral vectors and will be useful in identification and isolation of cells transfected in vitro and cells expressing transgenic or gene-targeted constructs in vivo.

Arch Intern Med, 1997 Oct 27, 157(19), 2190 - 5
Risk factors for 30-day mortality in elderly patients with lower respiratory tract infection . Community-based study; Houston MS et al.; BACKGROUND: Pneumonia is a major cause of death in the elderly, but there are few studies of risk factors for death that include both ambulatory and nursing home patients . OBJECTIVE: To assess factors associated with 30-day mortality in a population-based study of older adults with lower respiratory tract infection . METHODS: Identification of (1) a previously identified retrospective cohort of all residents of Rochester, Minn, aged 65 years or older who experienced a first episode of pneumonia or bronchitis during a calendar year and (2) the risk factors associated with 30-day mortality through review of complete inpatient and ambulatory medical records . Logistic regression was used to identify significant independent risk factors for 30-day mortality . RESULTS: A total of 413 adults aged 65 years or older were identified . The independent factors for 30-day mortality were atypical symptoms (odds ratio {OR}, 4.98; 95% confidence interval {CI}, 2.14-11.60), neurologic illness (OR, 3.92; 95% CI, 1.47-6.59), current diagnosis of cancer (OR, 6.2; 95% CI, 2.40-15.99), and recent or current use of antibiotics (OR, 3.13; 95% CI, 1.45-6.77) . CONCLUSIONS: Malignancy and neurologic disease are well-recognized conditions that identify patients with lower respiratory tract infections who have a high risk of death within 30 days . An atypical presentation with confusion, lethargy, poor eating, or recent or current antibiotic use also identifies patients, with a high risk of 30-day mortality.

Hosp Pract (Off Ed), 1997 Oct 15, 32(10), 85 - 9, 92-4
Acute exacerbations of chronic bronchitis; Grossman RF; Not every patient with bronchitis needs to be treated with an antibiotic . When treatment is indicated, however, the regimen should be selected carefully . A simple four-part disease classification scheme serves as a practical aid for initial assessment of the patient and as a guideline for choosing therapy.

Schweiz Rundsch Med Prax, 1997 Jul 30, 86(31-32), 1215 - 9
{Fever and dry cough in a construction worker from Portugal}; Wiesli P et al.; A 33-year-old Portugese worker presented with a one-week history of nonproductive cough and fever . A presumptive diagnosis "viral infection of the respiratory tract" was made . However, because of persisting cough and fever further investigations were necessary, and finally Brucella melitensis was isolated in blood cultures . Three months before admission to the hospital the man was dressing the carcasses of a goat in Portugal and consumpted fresh goats milk cheese . Antibiotic therapy with Rifampicin and Trimethoprim/Sulfamethoxazol over 6 weeks improved the signs and symptoms of the infection.

Ned Tijdschr Geneeskd, 1997 May 17, 141(20), 989 - 92
{Summary of the updated guideline 'Gastric Complaints' of the Dutch College of General Practitioners}; Thomas S et al.; The Dutch College of General Practitioners recently updated its guideline 'Gastric complaints' . The main change concerns Helicobacter pylori infection diagnosis and treatment . In cases of functional dyspepsia with Helicobacter infection antibiotic eradication treatment is not advised . In patients with gastric complaints, three working diagnoses are presented: aspecific gastric complaints, ulcer complaints, reflux complaints . Endoscopy is given a more prominent role than in the previous version of the guideline . Criteria are given for discontinuation of unmotivated long-term use of antacid medication.

Minerva Pediatr, 1997 May, 49(5), 211 - 4
{Orbital cellulitis . A case report}; Tucciarone L et al.; This study describes the case of a 6 years old child, male, with orbital cellulitis and underlines the importance of an early diagnosis and therapy to avoid severe complications often present in this disease . Swelling and redness of the eyelid, pain and ophthalmoplegia are the first sign of an orbital cellulitis and they require rapid diagnostic procedure such as ultrasound and TC scan of the orbital region to evaluate the integrity of the profound orbital tissues . The child was admitted at the Department of Pediatrics, University "La Sapienza" of Rome and underwent an ultrasound, TC scan and serum exams which demonstrated the elevation of the sedimentation rate, reactive C protein and WBC plus the interesting of the profound orbital tissues . The child was treated with antibiotic and antiinflammatory therapy showing a complete recovery within 7 days . An ultrasound performed 7 days later demonstrated a complete resolution of the inflammatory process . In summary, this study would like to stress the necessity of an early diagnosis and an appropriate therapy in order to avoid the severe complications often present in children with orbital cellulitis.

Klin Monatsbl Augenheilkd, 1997 Jul, 211(1), 60 - 4
{Unilateral trigeminal nerve hypoplasia}; Ries MW et al.; BACKGROUND: Isolated unilateral corneal anaesthesia represents a very rare clinical entity . The underlying cause may be a hypoplasia of the trigeminal nerve . HISTORY AND CLINICAL FINDINGS: A 7 year old otherwise healthy boy presented with mixed conjunctival injection of the left eye, fluorescein-positive punctuate epithelial keratopathy of the cornea and a central corneal ulcer OS . History revealed intermittent, painless redness of the left eye since the age of 4 . Trigeminal defects caused by trauma or infection could be ruled out . Tyndall's phenomena was positive . There was no corneal sensitivity on the left side and facial sensitivity was reduced in all branches of the trigeminal nerve . All other ophthalmologic examination results were normal . Magnetic resonance tomography showed a hypoplastic left trigeminal nerve . Mesenchymal syndromes could be ruled out by neuropediatric examination . THERAPY AND CLINICAL COURSE: Treatment with prednisolone and antibiotic ointment and eye patching were performed . The ulcer healed completely and artificial tear substitution was given for prophylaxis . Follow-up examinations after 4 and 6 years showed no signs of inflammation . Biomicroscopy showed only mild fluorescein-positive corneal epitheliopathy . CONCLUSIONS: In cases with painless intermittent keratoconjunctivitis, sometimes associated with corneal ulceration, in early childhood, one should consider acquired or congenital trigeminal anaesthesia . This condition requires life-long corneal ulcer prophylaxis and regular ophthalmologic exams.

Drugs, 1997 Oct, 54(4), 571 - 80
Practical recommendations for the treatment of ascites and its complications; Bataller R et al.; Ascites is one of the earliest and most common complications of patients with cirrhosis, and is associated with complications such as dilutional hyponatraemia, renal dysfunction and spontaneous bacterial peritonitis . The treatment of ascites has been based on the combination of a low-sodium diet and the administration of diuretics . The reintroduction of paracentesis and the recent introduction of the transjugular intrahepatic portosystemic shunt (TIPS) are the most relevant innovations in the treatment of ascites during the past 2 decades . The development of ascites is closely related to renal disturbances of functional origin, including the hepatorenal syndrome . A new definition of hepatorenal syndrome has been proposed recently and 2 different types have been defined (type I or progressive, and type III or stable) . Although no effective therapy exists for this syndrome, the use of therapeutic methods (TIPS, vasoconstrictor agents, dialysis) to temporarily improve renal function and act as a 'bridge' to liver transplantation, may be of most benefit . The use of potent and safe antibiotics has improved the resolution rate and survival of patients with spontaneous bacterial peritonitis . In addition, the use of oral antibiotics will simplify the management of this condition in the near future . Finally, prophylactic antibiotic regimens represent a major step forwards in the prevention of spontaneous bacterial peritonitis in subsets of cirrhotic patients with a great risk of developing this complication.

BMJ, 1997 Aug 30, 315(7107), 505 - 10
Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia; Nacul LC et al.; OBJECTIVE: To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the standard treatment for childhood pneumonia . DESIGN: A randomised, double blind, placebo controlled trial . SETTING: Study children were recruited at a public hospital in Recife, north east Brazil, an area of marginal vitamin A deficiency . SUBJECTS: 472 children aged 6 to 59 months with clinical diagnosis of pneumonia . INTERVENTIONS: 200,000 IU (infants) or 400,000 IU (1-4 year olds) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses, in addition to the standard treatment . MAIN OUTCOME MEASURES: Duration of the episode and incidence of adverse outcomes . RESULTS: The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes . Children who received vitamin A, however, were less likely to have fever by day 3 (P = 0.008) and were 29% less likely to fail to respond to the first line antibiotic (P = 0.054) . CONCLUSION: There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode.

Respir Med, 1997 Aug, 91(7), 387 - 94
Phase 1 safety trial of Filgrastim (r-metHuG-CSF) in non-neutropenic patients with severe community-acquired pneumonia; deBoisblanc BP et al.; The objectives of the present study were to: (1) evaluate the safety of Filgrastim therapy in non-neutropenic patients with severe community-acquired pneumonia; (2) determine the absolute neutrophil count (ANC) response to various dosages of Filgrastim in non-neutropenic patients with active infection; and (3) describe the impact of therapy with Filgrastim in combination with antibiotics on selected pneumonia-related clinical parameters . The study design was an open-label, dose-ranging, clinical trial, set in the General Clinical Research Unit of a large, public community hospital . The study population consisted of 30 patients who had presented to the Emergency Department with severe, community-acquired pneumonia . One of five dosages (75, 150, 300, 450 or 600 micrograms day-1) of Filgrastim (r-metHuG-CSF) was given subcutaneously daily for 10 days, until discharge or until the absolute neutrophil count > 75 x 10(9) l(-1), whichever was earlier . Vital signs, pulse oximetry, arterial blood gases, daily complete blood counts with differential, serum chemistries, coagulation profiles, electrocardiograms, chest radiographs, plasma G-CSF concentrations and duration of hospitalization were measured . There was no evidence of Filgrastim-related lung injury or evidence of extra-pulmonary toxicity . There was no apparent dose-response effect of Filgrastim on pneumonia-related clinical variables . Dosages of Filgrastim between 150 and 600 micrograms day-1 had similar effects on increasing the ANC . Filgrastim appeared to be safe in non-neutropenic patients with severe, community-acquired pneumonia when given in dosages of 75-600 micrograms day-1 in combination with appropriate antibiotic therapy . Further study is needed to determine the effect of Filgrastim on morbidity, mortality and duration of symptoms in this patient populationPublication Types:

	Clinical Trial
	Clinical Trial, Phase I
	Controlled Clinical Trial

What Is Genome?, What Is Molecular Biology?, What Is Rhizobia?, What Is Genetic Engineering?, What Is Environmental Microbiology?, c, Microbes, c, Bacterium, a, Microorganisms, r, Bacteriology, e, Microbiology, r, Staphylococcus aureus, i, Geobacilli, n, Microorganism, s, Culture medium, i, Botulism, n, Fermentations, a, Prokaryotes, o, Antimicrobial, n, Antimicrobial, a, Yeasts, r, Clostridia, e, Cell cultures, e, Escherichia coli, c, Thermophiles, s, Escherichia coli, n, Activated sludge, c, Candida albicans, e, Escherichia coli, i, Antibiotics, s, Yeast, c, Minimum inhibiting concentration

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

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

Last modified: May 25, 2005