Optimising gut colonisation resistance against Clostridium difficile infection.

Clostridium difficile is the dominant cause of pseudomembranous colitis in nosocomial environments. C. difficile infection (CDI) generally affects elderly (≥65 years of age) hospital inpatients who have received broad-spectrum antimicrobial treatment. CDI has a 30 % risk of re-infection and a subsequent 60 % risk of relapse thereafter, leading to a high economic burden of over 7 billion pounds sterling and over 900,000 cases in the USA and Europe per annum. With the long-term consequences of faecal transplantation currently unknown, and limited spectrum of effective antibiotics, there is an urgent requirement for alternative means of preventing and treating CDI in high-risk individuals. Metagenomics has recently improved our understanding of the colonisation resistance barrier and how this could be optimised. pH, oxidation-reduction potentials and short-chain fatty acids have been suggested to inhibit C. difficile growth and toxin production in in vitro and in vivo studies. This review aims to pull together the evidence in support of a colonisation resistance barrier against CDI.

A review of infection control in community healthcare: new challenges but old foes.

The demographics of the healthcare population are changing, with an ever-greater proportion of people being treated outside the traditional hospital setting through community healthcare. This shift in the way that healthcare is delivered raises new concerns over community healthcare-associated infections (HCAIs). A literature search between 2000 and December 2013 was conducted in databases including PubMed, SciVerse ScienceDirect and Google Scholar. National and international guideline and policy documents were searched using Google. Many terms were used in the literature searches, including 'nosocomial', 'healthcare infection', 'community' and 'nursing home'. The rates of HCAI in community healthcare are similar to the rates found in the acute hospital setting, but the types of infection differ, with a greater focus on urinary tract infections (UTIs) in the community and ventilator-associated pneumonias in the hospital setting. Patients who acquire a community HCAI are more likely to exhibit reduced physical condition, have increased levels of morbidity and have higher mortality rates than individuals without infection. Infection control programmes have been developed worldwide to reduce the rates of hospital HCAIs. Such interventions are equally as valid in the community, but how best to implement them and their subsequent impact are much less well understood. The future is clear: HCAIs in the community are going to become an ever-increasing burden and it is critical that our approach to these infections is brought quickly in line with present hospital sector standards.

Transfer of micro-organisms from dry surface biofilms and the influence of long survival under conditions of poor nutrition and moisture on the virulence of Staphylococcusaureus.

BACKGROUND: Biofilms on dry hospital surfaces can enhance the persistence of micro-organisms on dry harsh clinical surfaces and can potentially act as reservoirs of infectious agents on contaminated surfaces. AIM: This study was conducted to quantify the transfer of viable Staphylococcus aureus cells from dry biofilms through touching and to investigate the impact of nutrient and moisture deprivation on virulence levels in S. aureus. METHODS: Dry biofilms of S. aureus ATCC 25923 and a defective biofilm-forming ability mutant, S. aureus 1132, were formed in 24-well plates under optimized conditions mimicking dry biofilm formation on clinical surfaces. Microbial cell transfer was induced through the touching of the dry biofilms, which were quantified on nutrient agar. To investigate the impact of nutrient and moisture deprivation on virulence levels, dry and standard biofilms as well as planktonic cells of S. aureus ATCC 25923 were inoculated into Galleria mellonella and their kill rates compared. FINDINGS: Results of this study showed that viable cells from dry biofilms of S. aureus ATCC 25923 were significantly more virulent and readily transferrable from dry biofilms through a touch test, therefore representing a greater risk of infection. The biofilm-forming capability of S. aureus strains had no significant impact on their transferability with more cells transferring when biofilm surfaces were wet. CONCLUSIONS: These findings indicate that dry biofilms on hospital surfaces may serve as a reservoir for the dissemination of pathogenic micro-organisms in hospitals, thus highlighting the importance of regular cleaning and adequate disinfection of hospital surfaces.

Disordered Toll-like receptor 2 responses in the pathogenesis of pulmonary sarcoidosis.

In this study, we hypothesized that the granulomatous disorder sarcoidosis is not caused by a single pathogen, but rather results from abnormal responses of Toll-like receptors (TLRs) to conserved bacterial elements. Unsorted bronchoalveolar lavage (BAL) cells from patients with suspected pulmonary sarcoidosis and healthy non-smoking control subjects were stimulated with representative ligands of TLR-2 (in both TLR-2/1 and TLR-2/6 heterodimers) and TLR-4. Responses were determined by assessing resulting production of tumour necrosis factor (TNF)-α and interleukin (IL)-6. BAL cells from patients in whom sarcoidosis was confirmed displayed increased cytokine responses to the TLR-2/1 ligand 19-kDa lipoprotein of Mycobacterium tuberculosis (LpqH) and decreased responses to the TLR-2/6 agonist fibroblast stimulating ligand-1 (FSL)-1. Subsequently, we evaluated the impact of TLR-2 gene deletion in a recently described murine model of T helper type 1 (Th1)-associated lung disease induced by heat-killed Propionibacterium acnes. As quantified by blinded scoring of lung pathology, P. acnes-induced granulomatous pulmonary inflammation was markedly attenuated in TLR-2(-/-) mice compared to wild-type C57BL/6 animals. The findings support a potential role for disordered TLR-2 responses in the pathogenesis of pulmonary sarcoidosis.

'Secondary biofilms' could cause failure of peracetic acid high-level disinfection of endoscopes.

INTRODUCTION: The reduced susceptibility of biofilms to disinfectants presents a challenge to the successful reprocessing of medical equipment. This study examined the effect of residual biomass remaining after previous disinfection with peracetic acid (PAA) on the tolerance of subsequent mature Pseudomonas aeruginosa biofilms to PAA. The effect of enzymatic degradation of specific components of the extracellular polymeric substance (EPS) of P. aeruginosa biofilm on the effectiveness of PAA disinfection was also evaluated. METHODS: The susceptibility of biofilm grown on the biomass of PAA-killed biofilm to PAA was compared with the PAA susceptibility of biofilm grown in wells of a 24-well plate by evaluating their viability using the plate count assay. The effect of PAA on biofilm biomass was measured using crystal violet quantification of total biofilm biomass, while its effect on the polysaccharide and protein components of biofilm EPS was quantified using the phenol-sulphuric acid assay or Bradford assay, respectively. A confocal microscope was used to visualize the distribution of living and dead cells in biofilms grown on residual biofilm biomass. FINDINGS: The presence of residual biomass from previously disinfected biofilms significantly enhanced the tolerance of subsequent biofilms. A 96-h-old 'secondary biofilm' formed on disinfected biomass survived PAA concentrations of 4000 ppm, which exceeds the concentrations used in practice for high-level disinfection. CONCLUSION: These observations indicate that, under certain circumstances, recolonization of residual EPS can cause failure of disinfection of medical equipment such as endoscopes, and emphasizes the importance of cleaning endoscopes prior to disinfection.

Multicenter external quality assessment of molecular methods for detection of human herpesvirus 6.

The purpose of this study was to evaluate the performance of laboratories for the detection and quantification of human herpesvirus 6 (HHV-6) by an external quality assessment (EQA) evaluation. The HHV-6 EQA panel consisted of eight samples containing various concentrations of HHV-6 type A (strain GS) or type B (strain Z29), two samples containing other herpesviruses (i.e., human cytomegalovirus [HCMV] and Epstein-Barr virus [EBV]), and two HHV-6-negative samples. Panel samples were prepared in human plasma, heat inactivated, and lyophilized. Panel distribution, data management, and analysis were coordinated by Quality Control for Molecular Diagnostics (QCMD), Glasgow, United Kingdom. Fifty-one laboratories participated and submitted 57 data sets. Eleven (19.3%) data sets were generated using conventional in-house assays, 11 (19.3%) data sets using commercial real-time PCR assays, and 35 (61.4%) data sets using in-house real-time PCR assays. The presence of HHV-6 DNA at viral loads exceeding 6,000 copies/ml was detected by all participants, and over 80% of the participants still reported correct qualitative results for the sample containing just over 200 copies/ml. The false-positivity rate was 1.8% for both the negative samples and the samples containing HCMV or EBV DNA. The majority (23/33; 69.7%) of quantitative data sets were generated using in-house real-time PCR assays. The standard deviations of the geometric means of the samples ranged from 0.5 to 0.7 log(10). The results of this first international EQA demonstrate encouraging analytical sensitivity for the detection of HHV-6-DNA in human plasma, although we observed extensive interlaboratory variation of quantitative HHV-6 DNA results. Standardization needs to be improved to allow further elucidation of the clinical significance of HHV-6 loads.

External quality assessment of the molecular diagnostics and genotyping of meticillin-resistant Staphylococcus aureus.

Two multicentre external quality assessments (EQA) for the molecular detection and genotyping of meticillin-resistant Staphylococcus aureus (MRSA) were arranged. Firstly, 11 samples containing various amounts of inactivated MRSA strains, meticillin-susceptible S. aureus (MSSA), meticillin-resistant coagulase-negative staphylococci (MRCoNS) or Escherichia coli were distributed to 82 laboratories. Samples containing 102 or 103 MRSA cells were correctly scored in only 16 and 46% of the datasets returned, respectively. Two of the used MSSA strains contained an SCCmec cassette lacking the mecA gene. There was a marked difference in the percentage of correct results for these two MSSA strains (37 and 39%) compared to the MSSA strain lacking the SCCmec cassette (88%). Secondly, a panel for MRSA genotyping, consisting of ten samples (two identical, three genetically related and five unique strains) was distributed to 19 laboratories. Seventy-three percent of the datasets recorded all samples correctly. Most pulsed-field gel electrophoresis (PFGE) protocols proved to be suboptimal, resulting in inferior resolution in the higher or lower fragment regions. The performance of molecular diagnostics for MRSA shows no significant changes since our first EQA in 2006. The first molecular typing results are encouraging. Both assessments indicate that programme expansion is required and that major performance discrepancies continue to exist.

A descriptive morphology of the ant genus Procryptocerus (Hymenoptera: Formicidae).

Morphology is the most direct approach biologists have to recognize uniqueness of insect species as compared to close relatives. Ants of the genus Procryptocerus possess important morphologic characters yet have not been explored for use in a taxonomic revision. The genus is characterized by the protrusion of the clypeus forming a broad nasus and antennal scrobes over the eyes. The toruli are located right posterior to the flanks of the nasus opposite to each other. The vertex is deflexed posteriorly in most species. An in-group comparison of the external morphology is presented focusing on the workers. A general morphology for gynes and males is also presented. Previously mentioned characters as well as new ones are presented, and their character states in different species are clarified. For the metasoma a new system of ant metasomal somite nomenclature is presented that is applicable to Aculeata in general. Finally, a Glossary of morphological terms is offered for the genus (available online). Most of the terminology can be used in other members of the Formicidae and Aculeata.

Drivers of Clostridioides difficile hypervirulent ribotype 027 spore germination, vegetative cell growth and toxin production in vitro.

OBJECTIVES: Clostridioides difficile infection (CDI) is a considerable healthcare and economic burden worldwide. Faecal microbial transplant remains the most effective treatment for CDI, but is not at the present time the recommended standard of care. We hereby investigate which factors derived from a healthy gut microbiome might constitute the colonization resistance barrier (CRB) in the gut, inhibiting CDI. METHODS: CRB drivers pH, short chain fatty acid (SCFA), and oxidation-reduction potential (ORP) were investigated in vitro using C. difficile NAP1/BI/027. Readouts for inhibitory mechanisms included germination, growth, toxin production and virulence gene expression. pH ranges (3-7.6), SCFA concentrations (25-200 mM) and ORP (-300 to 200 mV) were manipulated in brain heart infusion broth cultures under anaerobic conditions to assess the inhibitory action of these mechanisms. RESULTS: A pH < 5.3 completely inhibited C. difficile growth to optical density (OD) 0.019 vs. 1.19 for control pH 7.5. Toxin production was reduced to 25 units vs. 3125 units for pH 7.6 (1 in 5 dilutions). Virulence gene expression reduced by 150-fold compared with pH 7.6 (p < 0.05). Germination and proliferation of spores below pH 6.13 yielded an average OD of 0.006 vs. 0.99 for control. SCFA were potent regulators of toxin production at 25 mM and above (p < 0.05). Acetate significantly inhibited toxin production to 25 units independent of OD (0.8733) vs. control (OD 0.6 and toxin titre 3125) (p < 0.05). ORP did not impact C. difficile growth. CONCLUSIONS: This study highlights the critical role that pH has in the CRB, regulating CDI in vitro and that SCFA can regulate C. difficile function independent of pH.

Influence of delivery system on the efficacy of low concentrations of hydrogen peroxide in the disinfection of common healthcare-associated infection pathogens.

INTRODUCTION: The ability of healthcare-associated infection pathogens to survive on environmental surfaces is well known. Disinfection is employed to reduce or remove these pathogens but disinfection failures still occur. One method with the potential to improve disinfection efficacy is whole-room disinfection with hydrogen peroxide (H2O2). AIM: To determine the influence of delivery system on the efficacy of low-concentration H2O2 on common healthcare-associated infection pathogens. METHODS: SanoStatic (electrostatic spray) was compared with SanoFog (fogging) in terms of performance for delivery of 5% H2O2 and trace silver ions for disinfection. The bacterial test challenges were vancomycin-resistant Enterobacterales (VRE), extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBLK), carbapenemase-producing Enterobacterales (CPE), meticillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile spores, Bacillus atropheus and Geobacillus stearothermophilus commercial spore strips. FINDINGS: SanoFog and SanoStatic were effective when tested under the conditions of experimentation reported here. For VRE, ESBLK, CPE and MRSA, SanoFog and SanoStatic were comparable in performance. For C. difficile we concluded the following: SanoFog was most effective for disinfection of C. difficile spores when compared to SanoStatic. CONCLUSION: Whereas SanoFog and SanoStatic were effective against bacterial cells, the current practice of using SanoFog and SanoStatic together would be effective for disinfection of C. difficile spores based on investigations under the conditions of experimentation reported here. The spore strips results were not comparable to the results either for the vegetation cells (VRE, ESBLK, CPE, and MRSA) or for C. difficile spores.

HIV-1 drug resistance genotyping quality assessment: results of the ENVA7 Genotyping Proficiency Programme.

BACKGROUND: Drug-resistance testing plays a critical role in selection of optimal treatment regimens for HIV infected individuals. Laboratories performing testing must implement quality control measures including external quality assessment. OBJECTIVES: The ENVA7 Programme (2007) was organised by QCMD to assess the performance of laboratories testing for drug-resistance mutations in the HIV-1 Protease and Reverse Transcriptase genes. STUDY DESIGN: The ENVA7 panel consisted of 5 lyophilised plasma samples (HIV-1 subtypes B, C and F). The viruses harboured wild type or resistant genotypes at various positions of the PR and RT genes. All IAS-defined resistance-associated codons were scored in comparison to the consensus sequence for each sample using a scoring system developed to allow simple and standardised comparisons between laboratories and/or technologies. RESULTS: 111 laboratories from 44 countries participated of which 95 submitted 98 datasets. 36 datasets were generated using ViroSeq (Abbott), 27 using TruGene (Siemens) and 35 using in-house assays. CONCLUSIONS: All technologies successfully genotyped each of the panel samples, irrespective of the virus subtype. While the assays for genotypic HIV drug-resistance determination have evolved into reliable and technically capable procedures of generating high quality results, variation in the quality of results is still observed between laboratories.

Molecular detection and typing of influenza viruses: are we ready for an influenza pandemic?

BACKGROUND: We cannot predict when an influenza pandemic will occur or which variant of the virus will cause it. Little information is currently available on the ability of laboratories to detect and subtype influenza viruses including the avian influenza viruses. OBJECTIVES: To assess the ability of laboratories to detect and subtype influenza viruses. STUDY DESIGN: In 2006 QCMD distributed an External Quality Assessment panel for the molecular detection and haemagglutinin subtyping of influenza viruses to 87 laboratories in 34 countries Worldwide, which were given 6 weeks to return results. These data were analysed to assess laboratory performance. RESULTS: Influenza virus positive panel samples were correctly identified by 35-98% of laboratories. The correct haemagglutinin subtype was reported by 32-87% of laboratories that detected the virus: incorrect subtyping results included the reporting of avian influenza viruses as human strains and vice versa. Twelve laboratories reported false positives with some avian influenza viruses reported. CONCLUSIONS: These data suggest that improvements are needed in the molecular detection of influenza viruses and influenza virus A haemagglutinin subtyping. Only rapid and accurate identification of circulating pandemic influenza virus will ensure that the maximum time is available for intervention.

Surface disinfection challenges for Candida auris: an in-vitro study.

The emerging pathogenic multidrug-resistant yeast Candida auris is an important source of healthcare-associated infections and of growing global clinical concern. The ability of this organism to survive on surfaces and withstand environmental stressors creates a challenge for eradicating it from hospitals. A panel of C. auris clinical isolates was evaluated on different surface environments against the standard disinfectant sodium hypochlorite and high-level disinfectant peracetic acid. C. auris was shown to selectively tolerate clinically relevant concentrations of sodium hypochlorite and peracetic acid in a surface-dependent manner, which may explain its ability to successfully persist within the hospital environment.

Infection control implications of the laundering of ambulance staff uniforms and reusable mops.

There is a lack of published studies on laundering in ambulance services. We performed bacterial culture on soiled and unsoiled uniforms and reusable mop heads artificially contaminated with Escherichia coli, Staphylococcus aureus, and Clostridium difficile spores. Current laundering processes used for routine cleans in the ambulances appears, from our simulations, to be effective at reducing vegetative pathogenic bacteria to undetectable levels, <3.398log10 colony-forming units (S. aureus and E. coli). Reduced levels of C. difficile were still detected after laundering but the risk this poses for infection is unknown, as background levels of these spores in the environment are unknown.

Comment on "effect of a polarized hydrogen target on the polarization of a stored proton beam".

Meyer [Phys. Rev. E 50, 1485 (1994)] analyzed the filtering mechanism of polarizing a stored beam by scattering from an internal polarized target. We noticed in Meyer's derivation of Eq. (4) of that paper that he had added a new twist to an old argument [W. Brückner, Physics with Antiprotons at LEAR in the ACOL Era: Proceedings of the Third LEAR Workshop, Tignes, Savoie, France, January 19-26, 1985 (Editions Frontières, Gif-sur-Yvette, France, 1985), p. 245] by allowing some particles that are spin flipped to be kept in the beam. We show that this invalidates the old result and leads to a more complicated expression for the buildup of polarization.

Retrovirus-mediated expression of a DNA repair protein in bone marrow protects hematopoietic cells from nitrosourea-induced toxicity in vitro and in vivo.

Severe and delayed myelosuppression is a major side effect encountered with the clinical use of nitrosourea-type chemotherapeutic drugs. The DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) has been shown to repair nitrosourea-induced DNA damage. We therefore investigated the effect of expressing MGMT in hematopoietic cells (via retrovirus-mediated gene transfer) on nitrosourea-induced toxicity. A retroviral vector (N2/ZipPGK-MGMT) expressing the human MGMT cDNA from the phosphoglycerate kinase promoter was constructed. Infection of murine bone marrow with the N2/ZipPGK-MGMT retrovirus significantly increased the survival of murine bone marrow-committed progenitor cells following in vitro exposure to N-N'-bis(2-chloroethyl)-N-nitrosourea (BCNU, carmustine). MGMT gene transfer also protected murine hematopoietic cells in vivo in a murine model of BCNU-induced myelosuppression. The infusion of 4-6 x 10(6) N2/ZipPGK-MGMT-transduced bone marrow cells into mice every 2 weeks significantly increased peripheral leukocyte counts, platelet counts, and hematocrits compared to infusions of mock-infected bone marrow cells. In addition, bone marrow-committed progenitor cells from some recipient animals demonstrated increased resistance to BCNU in vitro when analyzed 2.5 months after initial treatment. The integration of the N2/ZipPGK-MGMT provirus in the spleen DNA from these animals correlated with committed progenitor cell resistance to BCNU. These data suggest that MGMT expression in hematopoietic progenitor and precursor cells protects against nitrosourea-induced toxicity and that gene transfer may prove useful in attempts to reduce nitrosourea-induced myelosuppression in the clinical setting.

Topotecan increases topoisomerase IIalpha levels and sensitivity to treatment with etoposide in schedule-dependent process.

To elucidate the effect of topoisomerase (Topo) I inhibitors in the modulation of Topo II levels and sensitivity to Topo II-directed drugs, athymic mice bearing SW480 human colon cancer xenografts were treated with simultaneous, subsequent, or distant doses of topotecan and etoposide. This in vivo study demonstrates that simultaneous administration of topotecan and etoposide results in an antagonistic response. In contrast, inhibition of Topo I by topotecan results in a compensatory increase in Topo II alpha levels associated with increasing sensitivity of tumors to subsequent treatment with the Topo II inhibitor etoposide. Furthermore, we show that Topo II alpha levels decline 5 days after the last dose of topotecan, resulting in restoration of the original response of the xenografts to etoposide. Thus, this study emphasizes the critical role of schedule dependency to optimize the effectiveness of combination chemotherapy with Topo I and Topo II inhibitors.

Bioaerosol sampling: sampling mechanisms, bioefficiency and field studies.

Investigations into the suspected airborne transmission of pathogens in healthcare environments have posed a challenge to researchers for more than a century. With each pathogen demonstrating a unique response to environmental conditions and the mechanical stresses it experiences, the choice of sampling device is not obvious. Our aim was to review bioaerosol sampling, sampling equipment, and methodology. A comprehensive literature search was performed, using electronic databases to retrieve English language papers on bioaerosol sampling. The review describes the mechanisms of popular bioaerosol sampling devices such as impingers, cyclones, impactors, and filters, explaining both their strengths and weaknesses, and the consequences for microbial bioefficiency. Numerous successful studies are described that point to best practice in bioaerosol sampling, from the use of small personal samplers to monitor workers' pathogen exposure through to large static samplers collecting airborne microbes in various healthcare settings. Of primary importance is the requirement that studies should commence by determining the bioefficiency of the chosen sampler and the pathogen under investigation within laboratory conditions. From such foundations, sampling for bioaerosol material in the complexity of the field holds greater certainty of successful capture of low-concentration airborne pathogens. From the laboratory to use in the field, this review enables the investigator to make informed decisions about the choice of bioaerosol sampler and its application.

A storage ring experiment to detect a proton electric dipole moment.

A new experiment is described to detect a permanent electric dipole moment of the proton with a sensitivity of 10-29 e ⋅ cm by using polarized "magic" momentum 0.7 GeV/c protons in an all-electric storage ring. Systematic errors relevant to the experiment are discussed and techniques to address them are presented. The measurement is sensitive to new physics beyond the standard model at the scale of 3000 TeV.

Multi-institutional phase I/II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung carcinoma.

PURPOSE: To determine the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP) and thoracic radiotherapy. PATIENTS AND METHODS: Thirty-one patients were enrolled onto this study. During the phase I section of this study, the dose of paclitaxel was escalated in groups of three or more patients. Cycles were repeated every 21 days. For cycles 1 and 2, paclitaxel was administered according to the dose-escalation schema at doses of 100, 135, or 170 mg/m(2) intravenously over 3 hours on day 1. Once the maximum-tolerated dose (MTD) of paclitaxel (for cycles 1 and 2, concurrent with radiation) was determined, that dose was used in all subsequent patients entered onto the phase II section of this study. For cycles 3 and 4, the paclitaxel dose was fixed at 170 mg/m(2) in all patients. On day 2, cisplatin 60 mg/m(2) was administered for all cycles. On days 1, 2, and 3, etoposide 60 mg/m(2)/d (cycles 1 and 2) or 80 mg/m(2)/d (cycles 3 and 4) was administered. Chest radiation was given at 9 Gy/wk in five fractions for 5 weeks beginning on day 1 of cycle 1. Granulocyte colony-stimulating factors were used during cycles 3 and 4 only. RESULTS: Twenty-eight patients were assessable. The MTD of paclitaxel was 135 mg/m(2), with the dose-limiting toxicity being grade 4 neutropenia. Cycles 1 and 2 were associated with grade 4 neutropenia in 32% of courses, with fever occurring in 7% of courses and grade 2/3 esophagitis in 13%. Cycles 3 and 4 were complicated by grade 4 neutropenia in 20% of courses, with fever occurring in 6% of courses and grade 2/3 esophagitis in 16%. The overall response rate was 96% (complete responses, 39%; partial responses, 57%). After a median follow-up period of 23 months (range, 9 to 40 months), the median survival time was 22.3 months (95% confidence interval, 15.1 to 34.3 months) CONCLUSION: The MTD of paclitaxel with radiation and EP treatment is 135 mg/m(2) given over 3 hours. In this schedule of administration, a high response rate and acceptable toxicity can be anticipated.