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Abstract Objective To determine the efficacy of antibacterial prophylaxis in preventing infectious complications after percutaneous endoscopic gastrostomy. Design Prospective, randomised, placebo controlled, double blind, multicentre study. Setting Departments of internal [...]

Flow cytometric immunophenotyping (FCI) is an integral part in the diagnosis and classification of hematologic malignancies. FCI results also influence therapeutic decisions and disease prognosis. ClearLLab LS is a 12‐antibody 10‐color cocktail provided in dry format designed as a screen for patients suspected of having hematolymphoid disease. A blinded comparison between ClearLLab LS, (CD8‐FITC, Kappa‐FITC,CD4‐PE, Lambda‐PE, CD19‐ECD, CD56‐PE‐Cy5.5, CD10‐PE‐Cy7, CD34‐APC, CD5‐APC‐A700, CD20‐APC‐A750, CD3‐PB, and CD45‐KrO), ClearLLab Reagents (five‐color, 17‐antibodies) and individual Laboratory Developed Tests (LDTs), was conducted at four laboratories. Evaluation of ClearLLab LS was performed on 210 specimens, compared to the five‐color ClearLLab Reagents (IVD and CE‐IVD), and a subset (n= 167) to LDTs. ClearLLab LS showed good agreement to ClearLLab Reagents in detecting the absence (104/104) or presence (106/106) of abnormal populations. Of specimens with abnormal populations the ClearLLab LS agreed with the ClearLLab Reagent for neoplasm maturity assessment (70/70 mature and 36/36 immature). Out of 167 specimens with LDTs results, 86 contained abnormal population(s), ClearLLab LS detected 82 (95.3%) of cases. Of the 4 cases not detected by ClearLLab LS, 3 were plasma cell neoplasms and 1 was a mature T cell malignancy. Eighty‐one samples with no hematological malignancy as analyzed by LDT were also negative by ClearLLab LS (100% agreement). ClearLLab LS agreed with LDTs assessment of neoplasms' maturity (55/55 mature and 27/27 immature). ClearLLab LS screening tube showed excellent agreement between ClearLLab Reagents and with LDT's. The presence of CD34 and CD10 in the tube allowed the detection of blast populations in several acute leukemias and myeloid neoplasms that were tested. © 2017 International Clinical Cytometry Society

RUNX1-mutated acute myeloid leukemia (AML) show a distinct pattern of genetic abnormalities and an adverse prognosis. We analyzed the impact of multiple RUNX1 mutations and RUNX1 wild-type (WT) loss in 467 AML with RUNX1 mutations (mut): (1) RUNX1 WT loss (n=53), (2) >1 RUNX1mut (n=94) and (3) 1 RUNX1mut (n=323). In 1 RUNX1mut, +8 was most frequent, whereas in WT loss +13 was the most abundant trisomy (+8: 66% vs 31%, P=0.022; +13: 15% vs 62%, P<0.001). Analyses of 28 genes in 163 selected cases revealed SRSF2 (39%), ASXL1 (36%), DNMT3A (19%), IDH2 (17%) and SF3B1 (17%) as most frequently mutated genes. RUNX1 WT loss showed a higher frequency of ASXL1mut compared with the other cases (50% vs 29%, P=0.009). Median overall survival (OS) in the total cohort was 14 months. WT loss (OS: 5 months) and >1 RUNX1mut (14 months) showed an adverse impact on prognosis compared with 1 RUNX1mut (22 months; P=0.002 and 0.048, respectively). Mutations in ASXL1 and ⩾2 additional mutations correlated with shorter OS (10 vs 18 months, P=0.028; 12 vs 20 months, P=0.017). Thus, the number of RUNX1mut, RUNX1 WT loss and the number and type of additional mutations is biologically and clinically relevant.

MYD88(myeloid differentiation primary response 88) is mutated in the majority of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (LPL); but also, albeit less frequently, in other B-cell malignancies, including chronic lymphocytic leukemia (CLL). This suggests MYD88as a central regulator of pathogenesis, but requests a broader approach to define diagnostically relevant genetic profiles for LPL and CLL. We identified the L265P hotspot mutation in 86% (n=67/78) of our LPL and 2% (n=12/767) of our CLL cohort. Importantly, in CLL (n=5), but also in LPL (n=4) other MYD88mutations were identified. MYD88-mutated LPL was characterized by CXCR4mutations (25%) and del(6q) (19%), whereas both aberrations were absent in the MYD88-unmutated LPL cases. MYD88-mutated CLL formed a prognostically favorable subset with a high frequency of del(13q), mutated IGHVstatus and no adverse aberrations (del(11q), del(17p), TP53mutations). MYD88-mutated CLL differed from LPL with respect to cytogenetic aberrations and the absence of CXCR4mutations. In both entities, based on mutation load evaluation, MYD88mutations were found to be present in the stem clone in each case, whereas CXCR4(LPL) and SF3B1(CLL) mutations also occurred in subclones only.

Alterations in TP53have been described in many cancer types including hematological neoplasms. We aimed at comparing TP53mutations (mut) and deletions (del) in a large cohort of patients with hematological malignancies (n=3307), including AML (n=858), MDS (n=943), ALL (n=358), CLL (n=1148). Overall, alterations in TP53were detected in 332/3307 cases (10%). The highest frequency was observed in ALL (total: 19%; mut+del: 6%; mut only: 8%; del only: 5%) and AML (total: 13%; mut+del: 5%; mut only: 7%; del only: 1%), whereas TP53alterations occurred less frequently in CLL (total: 8%) and MDS (total: 7%). TP53mutations were significantly more frequent in patients ⩾60 vs <60 years in AML (9% vs 2%, P<0.001) and ALL (12% vs 6%, P<0.001). TP53mut+del had a significant negative impact on overall survival in all entities, whereas differences were observed regarding TP53mut only or TP53del only: TP53mut only impacted survival in AML (36 vs 9 months, P<0.001) and MDS (65 vs 19 months, P<0.001), TP53del only in CLL (not reached vs 64 months, P=0.008) and MDS (65 vs 24 months, P=0.011). As substantial differences between the entities are observed regarding correlation to age and survival, we suggest evaluation of both TP53deletion and mutation status.

Acute myeloid leukemia (AML) can be grouped into morphologically or genetically defined subtypes. Today, the AML phenotype–genotype associations, that is, FAB/WHO (French–American–British/World Health Organization) definitions and recurrent molecular mutations, are not fully understood. Therefore, we evaluated the impact of molecular mutations on the AML differentiation stage by molecular profiling of 4373 adult de novoAML patients in 7 cytomorphological subtypes. We investigated mutations in 20 genes, including myeloid transcription factors (CEBPA, RUNX1), tumor suppressors (TP53, WT1), DNA modifiers (DNMT3A, IDH1/2, TET2), chromatin modifiers (ASXL1, MLL), signal transduction genes (FLT3, KRAS, NRAS) and NPM1. The most frequently mutated genes per cytomorphological subtype were RUNX1in M0 (43%), NPM1in M1 (42%), DNMT3Ain M2 (26%), NPM1in M4 (57%), M5a (49%) and M5b (70%) and TP53in M6 (36%). Although some gene mutations were frequent in several cytomorphological subtypes, a series of associations of co-occurring mutations with distinct phenotypes were identified for molecularly defined subcohorts. FLT3, NPM1and WT1mutations were associated with an immature phenotype in myeloblastic AML, whereas other combinations involving ASXL1, RUNX1, MLL-PTD, CEBPAor KRASwere more frequent in myeloblastic AML with maturation. Within the NPM1mutated subcohort, ASXL1mutations were significantly associated with a monoblastic differentiation and DNMT3Amutations with a monocytic phenotype.

We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects ?60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts ?5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P=0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P=0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P=0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes.

Pretreatment cytogenetics is an important parameter for risk stratification and therapy approach in acute lymphoblastic leukemia (ALL). However, in up to 30% of cases, chromosome banding analysis (CBA) fails or reveals a normal karyotype. To characterize the subset of ALL with normal karyotype or failed CBA, we performed fluorescence in situhybridization (FISH) or PCR for BCR-ABL1and MLLrearrangements as well as array comparative genomic hybridization (aCGH) in 186 adult patients. We further carried out FISH for MYCin cases with Burkitt leukemia phenotype. FISH or PCR revealed one of the respective rearrangements in 22% of patients. In 80% of cases, copy number variations (CNV) were identified by aCGH. In 22% of cases, all CNV were below the resolution of CBA. On the basis of results of FISH, RT-PCR and aCGH, patients were categorized into three groups. The novel subset of patients with submicroscopic CNV only showed an overall survival at 3 years of 84% compared with 64% for patients classified as adverse abnormalities and 77% for cases with other aberrations (P=0.046). Thus, ALL with non-informative CBA can be further classified by FISH and aCGH providing prognostic information, which may be useful for a more individualized therapy.

Ta2O5films of 10-150 nm thickness were prepared by oxygen-assisted pyrolytic LPCVD at 450-490°C from tantalum penta ethoxide and O2with N2diluent. Silicon wafers 150 mm in diameter were used as substrates with a novel LPCVD reactor. The films were annealed in dry O2at 700-800°C. Compositional, structural, and electrical evaluations demonstrate that these uniform, pure, and conformal Ta2O5films are a viable alternative dielectric suitable for advanced megabit DRAM applications.

To evaluate the acceptance and tolerability of the nH1N1 2009 vaccine in HIV-positive individuals. 758 patients were included in this prospective study. Different study populations were formed: The Tolerability Study Group consists of HIV-infected patients who visited three outpatient clinics (Cologne, Bonn, Freiburg) during a predefined time period. Patients were offered nH1N1 vaccination. Those accepting were administered a standard dose AS03 adjuvant nH1N1 vaccine. Questionnaires to report side effects occurring within 7 days after immunization were handed out. In a substudy conducted during the same time period, acceptance towards immunization was recorded. This Acceptance Study Group consists of all HIV-infected patients visiting the Cologne clinic. They were offered vaccination. In case of refusal, motivation was recorded. In the Tolerability Study Group, a total of 475 patient diaries returned in the three study centres could be evaluated, 119 of those (25%) reported no side effects. Distribution of symptoms was as follows: Pain 285/475 patients (60%), swelling 96 (20%), redness 54 (11%), fever 48/475 (10%), muscle/joint ache 173 (36%), headache 127 (27%), and fatigue 210 (44%). Association of side effects with clinical data was calculated for patients in Cologne and Bonn. Incidence of side effects was significantly associated with CDC stages A, B compared to C, and with a detectable viral load (> 50 copies/mL). No correlation was noted for CD4 cell count, age, gender or ethnicity. In the Acceptance Study Group, 538 HIV-infected patients were offered vaccination, 402 (75%) accepted, while 136 (25%) rejected. Main reasons for rejection were: Negative media coverage (35%), indecisiveness with preference to wait until a later date (23%), influenza not seen as personal threat (19%) and scepticism towards immunization in general (10%). A total of 622 HIV-infected patients were vaccinated against nH1N1-influenza in the three study centres. No severe adverse events were reported. The tolerability was in most parts comparable to general population. Acceptance rate towards influenza vaccination was high (75%). Those refusing the immunization mentioned negative media coverage as the major influence on their decision.

In order to modify the output characteristics of organic light‐emitting devices (OLEDs), the optical properties of an active layer within the device are patterned without introducing any thickness modulation. For this purpose a new conjugated copolymer, which serves as a hole‐transporting material and at the same time can be index patterned using UV techniques, is synthesized. Poly(VC‐co‐VBT) (VC: N‐vinylcarbazole; VBT: 4‐vinylbenzyl thiocyanate) is prepared by free‐radical copolymerization of VC and VBT. The material contains photoreactive thiocyanate groups that enable altering of the material's refractive index under UV illumination. This copolymer is employed as a patternable hole‐transporting layer in multilayer OLEDs. Refractive‐index gratings in poly(VC‐co‐VBT) are inscribed using a holographic setup based upon a Lloyd mirror configuration. The fourth harmonic of a Nd:YAG (YAG: yttrium aluminum garnet) laser (266 nm) serves as the UV source. In this way 1D photonic structures are integrated in an OLED containing AlQ3(tris(8‐hydroxyquinoline) aluminum) as the emitting species. It is assured that only a periodical change of the refractive index (Δn= 0.006 at λ = 540 nm) is generated in the active material but no surface‐relief gratings are generated. The patterned devices show more forward‐directed out‐coupling behavior than unstructured devices (increase in luminosity by a factor of five for a perpendicular viewing direction). This effect is most likely due to Bragg scattering. For these multilayer structures, optimum outcoupling was observed for grating periods Λ ∼ 390 nm.

Objectives: Recent studies have shown a beneficial impact of fluoroquinolones on infection-related morbidity and mortality for patients with haematological malignancies during neutropenia. Among the fluoroquinolones moxifloxacin currently provides one of the broadest spectra of antibacterial activity and may be suitable for prophylaxis during neutropenia.Patients and methods: In this controlled before and after observational study, moxifloxacin chemoprophylaxis was used during prolonged neutropenia in haemato-oncological patients (period 2; 282 episodes). Data were compared with two periods with levofloxacin prophylaxis, one preceding period (period 1; 399 episodes) and a post-observational period (period 3; 53 episodes). Endpoints for evaluation were the rates of Gram-negative and Gram-positive bacteraemia and infection-related mortality.Results: We found similar survival rates as compared with levofloxacin. The rate of Gram-negative bacteraemia was higher during prophylaxis with moxifloxacin (11%) when compared with levofloxacin (6% for period 1 and 6% for period 3). In addition we observed a marked increase in diarrhoea associated with Clostridium difficile toxin A (CDAD) after a formula change from levofloxacin to moxifloxacin (attack rate 6% versus 33%). A decrease was attained after changing back to levofloxacin and reinforcing hygienic measures (13%).Conclusions: During moxifloxacin prophylaxis, we observed a significantly increased incidence of Gram-negative bacteraemia and CDAD. Careful attention must be paid not to trade the particularly beneficial effects of fluoroquinolones in the neutropenic setting for such disadvantageous effects. Until further data are obtained, caution is warranted when applying fluoroquinolones with high anaerobic activity in the neutropenic setting.

Morbidity and mortality in patients with malignancies are increased by viral infections. These mostly are reactivations of asymptomatic latent infections. They primarily concern clinical entities associated with the reactivation of herpes viruses, such as varicella zoster virus (VZV) and cytomegalovirus (CMV). Respiratory tract infections caused by influenza, parainfluenza or respiratory syncytial virus (RSV) are less common. Since reactivation of latent infections has major clinical impact, antiviral prophylaxis is an attractive approach for patients expecting immunosuppression. The main risk factor for clinically relevant reactivation is profound disruption of cellular immune response. Duration and severity of chemotherapy induced neutropenia are of lesser importance. The risk of viral complications rises significantly in the presence of sustained suppression of T-cell function, e.g. in recipients of allogeneic stem cell transplants or of alemtuzumab (Campath-1H) antibody therapy. The objective of this guideline is to review the basis of prophylactic strategies and to provide recommendations for clinicians treating patients with haematological malignancies and solid tumors.

ABSTRACTHuman metapneumovirus (HMPV) was isolated from a 63-year-old multiple myeloma patient who had undergone hematopoietic stem cell transplantation and who presented with lower respiratory tract infection several weeks prior to the diagnosis of lung cancer. The isolate was phylogenetically and biologically characterized and compared to HMPV prototypes and recent pediatric isolates. Remarkably, it belonged to the novel genomic subgroup A2b.

Abstract: In order to simulate the turbulent combustion process occurring in spark-ignition (IC) engines, it is necessary to provide suitable and numerically economical models, the latter being particularly important in the application to industrial problems. Moreover, these models must deliver sufficiently accurate results for the unsteady operation of spark combustion engines, concerning variable geometries, temperatures, pressures and charge development in different configurations. In this work different turbulent combustion models for premixed hydrocarbon combustion are compared with respect to their ability to accurately predict the propagation of turbulent perfectly premixed flames. As a first configuration a cylinder of constant volume was studied. Transient calculations were used to simulate the propagation of the turbulent flame and to evaluate the resulting turbulent burning velocity. These calculations were performed for a perfect mixture of air and hydrocarbons at stoichiometric mixture and different initial conditions concerning pressure, temperature and turbulence intensity. As a second configuration a stationary turbulent bunsen-type flame with methane fuel was used to validate the turbulent combustion model of [Lindstedt and Vaos, Combust. Flame 116 (1999) 461] at different pressures. Calculated results were then compared to experimental data of [Kobayashi, Tamura, Maruta and Niioka. In: Proceedings of the 26th Symposium on Combustion, 1996, p. 389] and show excellent agreement for the turbulent burning velocity at several pressure levels using only a single set of model parameters.

Laterally patterning the emission color of polymer light‐emitting devices is one of the current technological challenges for their commercialization. Photopatterning is one of the most convenient approaches for the production of closely spaced, differently colored pixels, other than direct‐writing approaches such as ink‐jet printing. The photo‐induced addition of thiols to CC bonds (the thiol‐ene) reaction is here utilized to achieve photobleaching of poly(phenylenevinylene)‐type polymers. By exploiting the chemical selectivity of the UV‐induced thiol‐ene reaction, the emission color in a guest–host system is tuned from that of the guest to that of the host. It is demonstrated that the presented method can be applied for numerous energy‐transfer systems.

AbstractA comprehensive diagnosis in leukemia relies on a combination of several methods. Cytomorphology, cytochemistry, cytogenetics, fluorescence in situ hybridization, multiparameter flow cytometry, and molecular methods are applied in parallel. Recently, gene expression profiling using microarrays has made it possible to measure the expression of thousands of genes in one step. The respective specific signature leads to a molecular fingerprint of the tumor sample. Therefore, gene expression profiling may lead to a better molecular classification, insights into pathophysiology of malignant and benign diseases as well as to new treatment options. This can be approached best by using well-defined tumor subtypes. Thus, leukemias are a very informative model system. Furthermore, gene expression profiling may lead to new targeted therapies and can detect genes to be used for minimal residual disease studies. Very recent studies also mention the possibility of using gene expression profiling for prognostication. In conclusion, microarrays may lead to a single platform for leukemia diagnosis with quick and very robust and even cheaper results. Therefore, this new method should be further validated in parallel to the standard work-flow and has to be proven before substituting other methods in the future.

A styrene copolymer of 4-vinylbenzyl thiocyanate (PST-co-VBT) was employed as recording material for optical interference patterns with periods Λ &lt; 1 μm. Using lower intensity laser irradiation (4 mJ cm^-2, λ = 266 nm), refractive index gratings were produced in PST-co-VBT by an UV-induced photoisomerization SCN → NCS. Subsequent modification of the patterns with gaseous amines yielded surface relief gratings via the formation of derivatives of thiourea. Laser irradiation with higher pulse energies (7 mJ cm^-2, λ = 266 nm) directly produced surface relief gratings via laser ablation (modulation depth 30 nm). Also these gratings were reactive toward amine reagents and allowed a selective functionalization of the grooves of the relief (“reactive gratings”). Under selected conditions, a doubling of the grating frequency was achieved by postexposure modification with gaseous amines. Optically inscribed gratings in PST-co-VBT were employed as optical resonators for distributed feedback (DFB) lasing. With a laser dye (DCM) dissolved in PST-co-VBT, optically pumped DFB laser action was observed after inscribing index and relief gratings. The pumping threshold for lasing Ith was 250 nJ cm^-2 at λ = 532 nm.

The number of pseudoscalar mesons in the mass range from 1400 to 1500 MeV/c2has been a subject of considerable interest for many years, with several experiments having presented evidence for two closely spaced states. A new measurement of the reaction π−p→K+K−π0nhas been made at a beam energy of 18 GeV. A partial wave analysis of the K+K−π0system shows evidence for three pseudoscalar resonances, η(1295), η(1416), and η(1485), as well as two axial vectors, f1(1285), and f1(1420). Their observed masses, widths and decay properties are reported. No signal was observed for C(1480), an IGJPC=1+1−−state previously reported in φπ0decay.

ABSTRACTThe development of fluoroquinolone resistance in Escherichia colimay be associated with mutations in regulatory gene loci such as marRABthat lead to increased multidrug efflux, presumably through activation of expression of the AcrAB multidrug efflux pump. We found that multidrug-resistant (MDR) phenotypes with enhanced efflux can also be selected by fluoroquinolones frommarRAB- or acrAB-inactivated E. coliK-12 strains having a single mutation in the quinolone-resistance-determining region of gyrA. Mutant 3-AG100MKX, obtained from a marknockout strain after two selection steps, showed enhanced expression of acrBin a reverse transcriptase PCR associated with insertion of IS186into the AcrAB repressor gene acrR. In vitro selection experiments with acrABknockout strains yielded MDR mutants after a single step. Enhanced efflux in these mutants was due to increased expression of acrEFand associated with insertion of IS2 into the upstream region ofacrEF, presumably creating a hybrid promoter. These observations confirm the importance of efflux-associated nontarget gene mutations and indicate that transposition of genetic elements may have a role in the development of fluoroquinolone resistance in E. coli.

Abstract: Purpose: To further define the most appropriate way of choosing the dose of carboplatin. Patients and methods: The pharmacokinetics of carboplatin were analyzed in 30 patients with advanced lung cancer receiving a total of 48 cycles of carboplatin plus paclitaxel/docetaxel combination chemotherapy. Platin concentrations of ultrafiltrated plasma and urine samples were determined by flameless atomic absorption spectrometry. A multiple regression analysis was performed for interactions between pharmacokinetic parameters and pretreatment characteristics. Results: Using a two-compartment-model, the following parameters were obtained (mean, coefficient of variation): initial half-life, 0.903 h (48%); terminal half-life, 13.6 h (116%); maximum plasma concentration (Cmax), 38.5 μM (86%); AUC, 111.9 μM/h (86%); volume of distribution, 411 l (130%); total clearance (Ct), 579 ml/min (75%); renal clearance (Cr), 453 ml/min (80%); renal elimination, 76% of dose (17%). In the univariate analysis, age was significantly related to Cmax (P=0.0303), AUC (P=0.0050), Ct (P=0.0020), Cr (P=0.0092). Plasma creatinine (Crp) was related to Cmax (P=0.0228), and 1/[Crp] was related to Cmax (P=0.0015) and AUC (P=0.0054), while body weight was related to Cmax (P=0.0365). No interaction with the schedule of application of the two drugs was observed. In the multivariate analysis, factors significantly related to AUC were 1/[Crp] (P < 0.01) and age (P < 0.01). Crp (P < 0.05) and 1/[Crp] (P < 0.01) were significantly associated with Cmax. Conclusions: These data stress the importance of dosing carboplatin according to renal function and age and warrant further analyses to validate this concept prospectively.

Hypoglycemia is known to decrease the body temperature and to stimulate counterregulatory hormone secretion. Although it is well established that antecedent hypoglycemia reduces the hormonal response to subsequent hypoglycemia, the effects of antecedent hypoglycemia on the subsequent hypothermic response are obscure. In the present study, body temperature was measured orally during a total of 90 glucose clamp experiments in 45 healthy men. The clamps lasted 6 hours and were performed under 6 different experimental conditions: a euglycemic clamp with a low rate of insulin infusion, 1.5 mU/kg . min (low insulin-eu), a euglycemic clamp with a high rate of insulin infusion, 15.0 mU/kg . min (high insulin-eu), a hypoglycemic clamp with a low rate of insulin infusion, 1.5 mU/kg . min (low insulin-hypo), a hypoglycemic clamp with a high rate of insulin infusion, 15.0 mU/kg . min (high insulin-hypo), and 2 hypoglycemic clamps following an antecedent 2.5-hour hypoglycemia (56 mg/dL) induced by either a low (1.5 mU/kg . min, low insulin-ante-hypo) or a high (15.0 mU/kg . min, high insulin-ante-hypo) rate of insulin infusion. Plasma glucose was maintained normal during the euglycemic clamps and was decreased stepwise during the hypoglycemic clamps (76 -> 66 -> 56 -> 46 mg/dL). During the hypoglycemic clamps, body temperature decreased by 0.26^o +/- 0.09^oC in low insulin-hypo, 0.28^o +/- 0.09^oC in high insulin-hypo, 0.29^o +/- 0.09^oC in low insulin-ante-hypo, and 0.41^o +/- 0.11^oC in high insulin-ante-hypo (all P < .01). There were no differences in the hypothermic response to hypoglycemia among the different hypoglycemic conditions (P > .1 for all comparisons). In contrast, body temperature remained unchanged during the euglycemic clamps, so the changes in body temperature differed significantly during the euglycemic clamps versus the hypoglycemic clamps (P < .05 for all comparisons). The data show that the body temperature decreases during hypoglycemia and this decrease is influenced neither by antecedent hypoglycemia nor by circulating insulin levels.

A photochemical technique for the modification of polyethylene (PE) surfaces was developed. Polyethylene samples were irradiated with UV light in a gas atmosphere containing SO2 and air to achieve a photosulfonation of the surface. The introduction of sulfonic acid groups (−SO3H) onto the PE surface was proved by Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. The influence of the gas composition and the UV irradiation time on the modification reaction were studied by means of contact angle measurements, FTIR spectroscopy, and dyeing with methylene blue. The hydrophilicity of the PE surface increased considerably compared to unreacted PE. The depth of photomodification amounted to several micrometers. A patterned surface modification was obtained by mask projection. The presented method of surface modification is carried out under atmospheric pressure and is considered to be an inexpensive alternative to plasma modification techniques. Because of the large depth of modification, the process may also be useful for the modification of membranes and&sbd;in combination with projection lithography&sbd;for the manufacture of gratings in thin polymer films (as required for holographic recordings and distributed feedback lasers).

ABSTRACTMutations in loci other than genes for the target topoisomerases of fluoroquinolones, gyrAand parC, may play a role in the development of fluoroquinolone resistance inEscherichia coli. A series of mutants with increasing resistance to ofloxacin was obtained from an E. coliK-12 strain and five clinical isolates. First-step mutants acquired agyrAmutation. Second-step mutants reproducibly acquired a phenotype of multiple antibiotic resistance (Mar) and organic solvent tolerance and showed enhanced fluoroquinolone efflux. None of the second-step mutants showed additional topoisomerase mutations. All second-step mutants showed constitutive expression of marAand/or overexpressed soxS. In some third-step mutants, fluoroquinolone efflux was further enhanced compared to that for second-step mutants, even when the mutant had acquired additional topoisomerase mutations. Attempts to circumvent the second-step Mar mutation by induction of the marlocus with sodium salicylate and thus to select for pure topoisomerase mutants at the second step were not successful. At least in vitro, non-target gene mutations accumulate in second- and third-step mutants upon exposure to a fluoroquinolone and typically include, but do not appear to be limited to, mutations in the maror soxregulons with consequent increased drug efflux.