Impact of an evidence-based intervention on urinary catheter utilization, associated process indicators, and infectious and non-infectious outcomes.

BACKGROUND: Multi-centre intervention studies tackling urinary catheterization and its infectious and non-infectious complications are lacking. AIM: To decrease urinary catheterization and, consequently, catheter-associated urinary tract infections (CAUTIs) and non-infectious complications. METHODS: Before/after non-randomized multi-centre intervention study in seven hospitals in Switzerland. Intervention bundle consisting of: (1) a concise list of indications for urinary catheterization; (2) daily evaluation of the need for ongoing catheterization; and (3) education on proper insertion and maintenance of urinary catheters. The primary outcome was urinary catheter utilization. Secondary outcomes were CAUTIs, non-infectious complications and process indicators (proportion of indicated catheters and frequency of catheter evaluation). FINDINGS: In total, 25,880 patients were included in this study [13,171 at baseline (August-October 2016) and 12,709 post intervention (August-October 2017)]. Catheter utilization decreased from 23.7% to 21.0% (P=0.001), and catheter-days per 100 patient-days decreased from 17.4 to 13.5 (P=0.167). CAUTIs remained stable at a low level with 0.02 infections per 100 patient-days (baseline) and 0.02 infections (post intervention) (P=0.98). Measuring infections per 1000 catheter-days, the rate was 1.02 (baseline) and 1.33 (post intervention) (P=0.60). Non-infectious complications decreased significantly, from 0.79 to 0.56 events per 100 patient-days (P<0.001), and from 39.4 to 35.4 events per 1000 catheter-days (P=0.23). Indicated catheters increased from 74.5% to 90.0% (P<0.001). Re-evaluations increased from 168 to 624 per 1000 catheter-days (P<0.001). CONCLUSION: A straightforward bundle of three evidence-based measures reduced catheter utilization and non-infectious complications, whereas the proportion of indicated urinary catheters and daily evaluations increased. The CAUTI rate remained unchanged, albeit at a very low level.

Colonization with resistant microorganisms in patients transferred from abroad: who needs to be screened?

BACKGROUND: While multi-drug resistant organisms (MDRO) are a global phenomenon, there are significant regional differences in terms of prevalence. Traveling to countries with a high MDRO prevalence increases the risk of acquiring such an organism. In this study we determined risk factors for MDRO colonization among patients who returned from a healthcare system in a high-prevalence area (so-called transfer patients). Factors predicting colonization could serve as screening criteria to better target those at highest risk. METHODS: This screening study included adult patients who had been exposed to a healthcare system abroad or in a high-prevalence region in Switzerland over the past six months and presented to our 950-bed tertiary care hospital between January 1, 2012 and December 31, 2013, a 24-month period. Laboratory screening tests focused on Gram-negative MDROs and methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: A total of 235 transfer patients were screened and analyzed, of which 43 (18 %) were positive for an MDRO. Most of them yielded Gram-negative bacteria (42; 98 %), with only a single screening revealing MRSA (2 %); three screenings showed a combination of Gram-negative bacteria and MRSA. For the risk factor analysis we focused on the 42 Gram-negative MDROs. Most of them were ESBL-producing Escherichia coli and Klebsiella pneumoniae while only two were carbapenemase producers. In univariate analysis, factors associated with screening positivity were hospitalization outside of Europe (p < 0.001), surgical procedure in a hospital abroad (p = 0.007), and - on admission to our hospital - active infection (p = 0.002), antibiotic treatment (p = 0.014) and presence of skin lesions (p = 0.001). Only hospitalization outside of Europe (Odds Ratio, OR 3.2 (95 % CI 1.5- 6.8)) and active infection on admission (OR 2.7 (95 % CI 1.07- 6.6)) remained as independent predictors of Gram-negative MDRO colonization. CONCLUSION: Our data suggest that a large proportion of patients (i.e., 82 %) transferred to Switzerland from hospitals in high MDRO prevalence areas are unnecessarily screened for MDRO colonization. Basing our screening strategy on certain criteria (such as presence of skin lesions, active infection, antibiotic treatment, history of a surgical procedure abroad and hospitalization outside of Europe) promises to be a better targeted and more cost-effective strategy.

The neuropsychological profile of patients with 3-methylglutaconic aciduria type III, Costeff syndrome.

Costeff syndrome is a rare genetic neuro-ophthalmological syndrome consisting of early-onset bilateral optic atrophy along with a progressive complex motor disorder with elevated levels of urinary 3-methylglutaconic acid and 3-methylglutaric acid. While borderline to mild cognitive deficits have been considered to be common in patients with this syndrome, a comprehensive cognitive assessment has never been performed. The aim of the current study was to explore the cognitive profile associated with Costeff syndrome. Sixteen adult patients diagnosed with Costeff syndrome were administered a neuropsychological test battery that was composed of standardized verbal tests adapted for the blind. General intelligence ranged from average to borderline, with a group mean consistent with intact general cognitive functioning (VIQmean = 85, z = -1) in the low-average range of the general population. The auditory immediate and delayed memory indexes were in the average range and were significantly higher than the general cognitive functioning, whereas the working memory index was significantly lower than the general cognitive functioning. Adult patients with Costeff syndrome have intact global cognition and learning abilities and strong auditory memory performance. © 2015 Wiley Periodicals, Inc.

Neuropsychological follow-up at school age of children with asymmetric ventricles or unilateral ventriculomegaly identified in utero.

OBJECTIVE: To examine the long-term neuropsychological outcome of children with a prenatal diagnosis of asymmetric ventricles or unilateral ventriculomegaly. DESIGN: A clinic-based neuropsychological study. SETTING: Paediatric neurology clinic. POPULATION: Thirty-three of 41 children, previously assessed at kindergarten age, with asymmetric ventricles or unilateral ventriculomegaly identified in utero, were recruited at school age for a neuropsychological follow-up. METHODS: All children, 9-11 years of age, underwent a battery of neuropsychological tests and the parents completed behavioural rating questionnaires. MAIN OUTCOME MEASURES: Results of the neuropsychological assessment and parents' questionnaires. RESULTS: There were no significant differences between children diagnosed with either asymmetric ventricles or unilateral ventriculomegaly in most parameters relative to the general population; the full-scale IQ scores were 103.13 ± 12.43 and 103.56 ± 10.5, respectively. A significantly lower performance was found only on one measure of attention among the unilateral ventriculomegaly group and on writing speed tasks among the asymmetric ventricles group. Both study groups showed significantly higher scores than expected in the normal population on a verbal fluency test. Comparison of both groups combined with the normative population yielded significantly lower scores only in attention tests. Yet, the clinical population showed significantly higher scores on writing accuracy, processing speed and verbal fluency and lower rates of executive dysfunction. CONCLUSIONS: Asymmetric ventricles or unilateral ventriculomegaly identified in utero does not appear to affect long-term mental development and school achievements. Further prospective research on a larger sample is needed in order to confirm our findings.

Serological diagnosis of echinococcosis: the diagnostic potential of native antigens.

PURPOSE: Human alveolar (AE) and cystic echinococcosis (CE) caused by the metacestode stages of Echinococcus multilocularis and E. granulosus, respectively, lack pathognomonic clinical signs. Diagnosis therefore relies on the results of imaging and serological studies. The primary goal of this study was to evaluate the efficacy of several easy-to-produce crude or partially purified E. granulosus and E. multilocularis metacestode-derived antigens as tools for the serological diagnosis and differential diagnosis of patients suspicious for AE or CE. METHODS: The sera of 51 treatment-naïve AE and 32 CE patients, 98 Swiss blood donors and 38 patients who were initially suspicious for echinococcosis but suffering from various other liver diseases (e.g., liver neoplasia, etc.) were analysed. RESULTS: According to the results of enzyme-linked immunosorbent assays (ELISA), metacestode-derived antigens of E. granulosus had sensitivities varying from 81 to 97% and >99.9% for the diagnosis of CE and AE, respectively. Antigens derived from E. multilocularis metacestodes had sensitivities ranging from 84 to 91% and >99.9% for the diagnosis of CE and AE, respectively. Specificities ranged from 92 to >99.9%. Post-test probabilities for the differential diagnosis of AE from liver neoplasias, CE from cystic liver lesions, and screening for AE in Switzerland were around 95, 86 and 2.2%, respectively. Cross-reactions with antibodies in sera of patients with other parasitic affections (fasciolosis, schistosomosis, amebosis, cysticercosis, and filarioses) did occur at variable frequencies, but could be eliminated through the use of confirmatory testing. CONCLUSIONS: Different metacestode-derived antigens of E. granulosus and E. multilocularis are valuable, widely accessible, and cost-efficient tools for the serological diagnosis of echinococcosis. However, confirmatory testing is necessary, due to the lack of species specificity and the occurrence of cross-reactions to other helminthic diseases.

Alpha-1-Fetoprotein (AFP): international proficiency study with different test systems.

BACKGROUND: The present proficiency study aimed to elucidate the comparability and reliability of test systems for the determination of AFP concentrations. METHODS: 25 laboratories using 8 different commercial test systems used liquid BIOREF-AFP control serum in their routine internal quality control over a period of one year. For statistical analysis the results were collected centrally. RESULTS: The statistical analysis of the test results revealed considerable variation for the different laboratories. The deviations of the mean values of different laboratories from the overall mean value varied between 0.1 and 26.1%, and for most of the laboratories the deviation was round about 10%. The precision of measured values in the individual laboratories was in most cases acceptable: Nevertheless, the coefficients of variation of the individual laboratories ranged from 13 to 16.1%. CONCLUSIONS: In conclusion, this study indicates that AFP results vary between different laboratories albeit an international standard for AFP is available. Therefore, every laboratory should participate in external ring studies and should use a quality control serum independent of the test kit manufacturer for the internal quality control.

Pulmonary toxoplasmosis, a rare but severe manifestation of a common opportunistic infection in late HIV presenters: report of two cases.

Pulmonary toxoplasmosis is rare, particularly in the era of highly active antiretroviral therapy (HAART). Here, we describe two severe cases in patients not known to be HIV-infected. In both patients, early diagnosis and therapy led to a favourable outcome. Pulmonary toxoplasmosis should be considered in the differential diagnosis in potentially HIV-infected patients with respiratory symptoms.

Developmental outcome of isolated fetal macrocephaly.

OBJECTIVE: To evaluate the neurodevelopmental outcome of children with prenatally diagnosed head circumference greater than 2 SD above the mean for gestational age and no associated anomalies detected by ultrasound. METHODS: This was a retrospective study of 17 fetuses, diagnosed in the third trimester by ultrasound as having isolated macrocephaly, defined as head circumference greater than 2 SD above the mean for gestational age. We evaluated their performance on a standardized neuropsychological battery at age 2-7 years, and compared them with 17 normocephalic children. RESULTS: The range of fetal head circumference in the study group was 2.0-2.9 SD. There were no significant differences between the groups in cognitive, language and motor domains. The study group scored significantly worse than the control group on three parameters, reflecting executive functioning, behavior and social-emotional development. Children with familial macrocephaly showed significantly better executive functioning compared with children with non-familial macrocephaly. Multiple linear regression analysis found paternal head circumference to be the only significant variable in positively predicting the cognitive functioning of the child. CONCLUSIONS: The finding in utero of a head circumference 2-3 SD above the mean for gestational age with no associated anomalies does not appear to be a significant risk factor for abnormal long-term neuropsychological development. Our study provides information important for parental counseling prenatally.

Developmental outcome of isolated fetal microcephaly.

OBJECTIVE: To assess the neurodevelopmental outcome of children with prenatally diagnosed isolated microcephaly defined as head circumference more than 2 SD below the gestational mean. METHODS: Children aged 2-6 years who had been diagnosed in utero as having head circumference measurements more than 2 SD below the gestational mean were compared with normocephalic children, utilizing a standard neuropsychological battery. Comparisons were also made within the study group. RESULTS: HCs were between -2 and -4.8 SD, only one fetus having a HC below -3 SD. Children with a prenatal head circumference between 2 SD and 3 SD below the gestational mean did not differ significantly from the control group regarding cognitive, language and motor functioning. However, they exhibited more behavioral-emotional problems. There were no significant differences between children who had suffered from intrauterine growth restriction and those who had not, or between those with familial and those with non-familial microcephaly. Nevertheless, linear regression analysis showed that head circumference in utero helps predict cognitive functioning later in life. CONCLUSIONS: Prenatally diagnosed head circumference between 2 SD and 3 SD below the gestational mean is not a risk factor for later abnormal neuropsychological development.

Precision and long-term stability of different estradiol immunoassays assessed in a multi-center quality control study.

BACKGROUND: Because of the vast range of physiological relevant estradiol concentrations the requirements to be met by an estradiol assay are high. In the present study the performance of various commercially available estradiol assays was evaluated with regard to imprecision and long-term stability. METHODS: Precision and long-term stability of 7 commercially available estradiol immunoassays were assessed in a multi-centre quality control study based on the repeated measurement of liquid BIOREF estradiol control sera by 18 laboratories during a 14-month study period. RESULTS: The mean estradiol concentrations determined in 594 runs performed for each control level were 71 pg/ml, 349 pg/ml and 676 pg/ml. A high variation was found for the method specific mean values calculated from all results measured with the same method, which ranged between 32 - 90 pg/ml, 187 - 392 pg/ml and 373 - 790 pg/ml, resulting in a similar high inter-laboratory variation with coefficients of variation (CVs) of 25.0%, 16.7% and 17.5%. In contrast, the intra-laboratory variation of estradiol values as well as the variation of values measured with the same method were found to be considerably lower with coefficients of variation < 10% for most laboratories and methods; only the low control level was measured with CV values > 10% by the majority of laboratories and methods. For none of the laboratories a tendency was observed in the results from beginning to end of the 14 month study period indicating a high uniformity in assay production and a good long-term stability of the control material used. CONCLUSIONS: The present data demonstrate that also with the currently available estradiol immunoassays the comparability of results measured with different methods is limited. With most assays very low estradiol concentrations, as observed in postmenopausal women, can be determined only with a precision which is not adequate for clinical assessment.

Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study.

BACKGROUND: Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine. The biochemical variable procalcitonin (PCT) is known to indicate systemically relevant bacterial infections with high accuracy. In the present study, we aimed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. PATIENTS AND METHODS: Patients were randomly assigned to a PCT-guided or a control group requiring antibiotic treatment. All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum. In the PCT-guided group, antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either <1 ng/ml or decreased to <35% of the initial concentration within three consecutive days. In the control group, antibiotic treatment was directed by empirical rules. RESULTS: The PCT-guided group (n = 14 patients) and the control group (n = 13 patients) did not differ in terms of biological variables, underlying diseases, and overall disease severity. PCT guidance led to a significant reduction of antibiotic treatment from 6.6 +/- 1.1 days (mean +/- SD) compared with 8.3 +/- 0.7 days in control patients (p < 0.001) along with a reduction of antibiotic treatment costs of 17.8% (p < 0.01) without any adverse effects on outcome. CONCLUSIONS: Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine.

[Antibiotic treatment of surgical intensive care patients: procalcitonin to guide duration of therapy]. / Antibiotikatherapie bei operativen Intensivpatienten: Prokalzitonin zur Steuerung der Therapiedauer.

The development of resistance by infective bacterial species is an incentive to reconsider the indications and administration of available antibiotics. Correct recognition of the indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care situation. There has as yet been no clinical chemical parameter which is capable of specifically distinguishing a bacterial infection from a viral or non-infectious inflammatory reaction, but it now appears that procalcitonin (PCT) offers this possibility. The present study was intended to clarify whether PCT can be used to guide antibiotic therapy in surgical intensive care patients. A total of 110 patients in a surgical intensive care ward receiving antibiotic therapy after confirmed infection or a high grade suspicion of infection were enrolled in this study. In 57 of these patients a new decision was reached each day as to whether the antibiotic therapy should be continued after daily PCT determination and clinical assessment. The control group consisted of 53 patients with a standardized duration of antibiotic therapy over 8 days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter compared to controls (5.9+/-1.7 vs. 7.9+/-0.5 days, p<0.001) without unfavorable effects on clinical outcome.

A multi-frequency pulse EPR and ENDOR approach to study strongly coupled nuclei in frozen solutions of high-spin ferric heme proteins.

In spite of the tremendous progress in the field of pulse electron paramagnetic resonance (EPR) in recent years, these techniques have been scarcely used to investigate high-spin (HS) ferric heme proteins. Several technical and spin-system-specific reasons can be identified for this. Additional problems arise when no single crystals of the heme protein are available. In this work, we use the example of a frozen solution of aquometmyoglobin (metMb) to show how a multi-frequency pulse EPR approach can overcome these problems. In particular, the performance of the following pulse EPR techniques are tested: Davies electron nuclear double resonance (ENDOR), hyperfine correlated ENDOR (HYEND), electron-electron double resonance (ELDOR)-detected NMR, and several variants of hyperfine sublevel correlation (HYSCORE) spectroscopy including matched and SMART HYSCORE. The pulse EPR experiments are performed at X-, Q- and W-band microwave frequencies. The advantages and drawbacks of the different methods are discussed in relation to the nuclear interaction that they intend to reveal. The analysis of the spectra is supported by several simulation procedures, which are discussed. This work focuses on the analysis of the hyperfine and nuclear-quadrupole tensors of the strongly coupled nuclei of the first coordination sphere, namely, the directly coordinating heme and histidine nitrogens and the 17O nucleus of the distal water ligand. For the latter, 17O-isotope labeling was used. The accuracy of our results and the spectral resolution are compared in detail to an earlier single-crystal continuous-wave ENDOR study on metMb, and it will be shown how additional information can be obtained from the multi-frequency approach. The current work is therefore prone to become a template for future EPR/ENDOR investigations of HS ferric heme proteins for which no single crystals are available.

Transient nucleation near the mean-field spinodal.

Nucleation is considered near the pseudo-spinodal in a one-dimensional phi{4} model with a nonconserved order parameter and long-range interactions. For a sufficiently large system or a system with slow relaxation to metastable equilibrium, there is a non-negligible probability of nucleation occurring before reaching metastable equilibrium. This process is referred to as transient nucleation. The critical droplet is defined to be the configuration of maximum likelihood that is dynamically balanced between the metastable and stable wells. Time-dependent droplet profiles and nucleation rates are derived, and theoretical results are compared to computer simulations. The analysis reveals a distribution of nucleation times with a distinct peak characteristic of a nonstationary nucleation rate. Under the quench conditions employed, transient critical droplets are more compact than the droplets found in metastable equilibrium simulations and theoretical predictions.

Neuropsychological outcome of children with asymmetric ventricles or unilateral mild ventriculomegaly identified in utero.

DESIGN: To assess the neuropsychological outcome of children with asymmetric ventricles and unilateral ventriculomegaly identified in utero. SETTING: Fetal neurology clinic. POPULATION: We assessed 21 children with asymmetric ventricles (group 1) and 20 children with unilateral ventriculomegaly (group 2) identified in utero and compared them with a group of 20 children with symmetric ventricles using a formal neuropsychological tool: the Bayley Scale of Infant Development II (BSID-II). MAIN OUTCOME MEASURES: The group of children with unilateral ventriculomegaly scored significantly lower than the control group on the mental developmental index (MDI) and on the behaviour rating scale (BRS) but not on the psychomotor index. The group of children with asymmetric ventricles did not differ significantly from the control group on either the MDI or psychomotor developmental index but differed from the latter on the BRS. Fifteen percent of the children in the asymmetric ventriculomegaly group performed two SDs below average compared with 4% of children in the asymmetrical ventricles group and none of the control. CONCLUSION: Our results indicate that prenatally observed unilateral ventriculomegaly is a significant risk factor for developmental delay. The mental and motor outcome of children with asymmetric ventricles is similar to that of the control group, but these children are at a significant risk for behavioural abnormalities.

Analyzing heme proteins using EPR techniques: the heme-pocket structure of ferric mouse neuroglobin.

In this work, an electron paramagnetic resonance (EPR) strategy to study the heme-pocket structure of low-spin ferric heme proteins is optimized. Frozen solutions of ferric mouse neuroglobin (mNgb) are analyzed by means of electron spin echo envelope modulation and pulsed electron-nuclear double resonance techniques. The hyperfine and nuclear quadrupole couplings of the directly coordinating heme and histidine nitrogens are derived and are discussed in comparison with known data of other ferric porphyrin compounds. In combination with the hyperfine matrices of the imidazole protons, the 14N EPR parameters reveal structural information on the heme pocket of mNgb that is in agreement with previous X-ray diffraction data on neuroglobins.

Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer.

Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression. In order to evaluate its potential as a prognostic marker, its protein levels were measured by ELISA in preoperative sera from 324 patients with colorectal cancer. The level of cathepsin H was significantly increased in patient sera, the median level was 8.4 ng/mL versus 2.1 ng/mL in 90 healthy blood donors (p < 0.0001). A weak association of cathepsin H levels was found with patient age (p = 0.02) but not with Dukes' stage, sex, or the level of carcinoembryonic antigen (CEA). In survival analysis a significant difference was found between the group of patients with low cathepsin H (first tertile) who had a poor prognosis and the remaining patients (p = 0.03). The risk of patients was further stratified when cathepsin H levels were combined with CEA. Patients with high CEA and low cathepsin H had the highest risk of death with a hazard ratio of 2.72 (95% CI 1.73-4.28), p < 0.0001. Our results show that the prognostic information of cathepsin H differs from that of the related cathepsins B and L and suggest different roles during the progression of malignant disease.

Numerical simulation of one- and two-dimensional ESEEM experiments.

Numerical simulation has become an indispensable tool for the interpretation of pulse EPR experiments. In this work it is shown how automatic orientation selection, grouping of operator factors, and direct selection and elimination of coherences can be used to improve the efficiency of time-domain simulations of one- and two-dimensional electron spin echo envelope modulation (ESEEM) spectra. The program allows for the computation of magnetic interactions of any symmetry and can be used to simulate spin systems with an arbitrary number of nuclei with any spin quantum number. Experimental restrictions due to finite microwave pulse lengths are addressed and the enhancement of forbidden coherences by microwave pulse matching is illustrated. A comparison of simulated and experimental HYSCORE (hyperfine sublevel correlation) spectra of ordered and disordered systems with varying complexity shows good qualitative agreement.

Highly efficient phosphodiester hydrolysis promoted by a dinuclear copper(II) complex.

The interaction of Cu(II) with the ligand tdci (1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol) was studied both in the solid state and in solution. The complexes that were formed were also tested for phosphoesterase activity. The pentanuclear complex [Cu(5)(tdciH(-2))(tdci)(2)(OH)(2)(NO(3))(2)](NO(3))(4).6H(2)O consists of two dinuclear units and one trinuclear unit, having two shared copper(II) ions. The metal centers within the pentanuclear structure have three distinct coordination environments. All five copper(II) ions are linked by hydroxo/alkoxo bridges forming a Cu(5)O(6) cage. The Cu-Cu separations of the bridged centers are between 2.916 and 3.782 A, while those of the nonbridged metal ions are 5.455-5.712 A. The solution equilibria in the Cu(II)-tdci system proved to be extremely complicated. Depending on the pH and metal-to-ligand ratio, several differently deprotonated mono-, di-, and trinuclear complexes are formed. Their presence in solution was supported by mass, CW, and pulse EPR spectroscopic study, too. In these complexes, the metal ions are presumed to occupy tridentate [O(ax),N(eq),O(ax)] coordination sites and the O-donors of tdci may serve as bridging units between two metal ions. Additionally, deprotonation of the metal-bound water molecules may occur. The dinuclear Cu(2)LH(-3) species, formed around pH 8.5, provides outstanding rate acceleration for the hydrolysis of the activated phosphodiester bis(4-nitrophenyl)phosphate (BNPP). The second-order rate constant of BNPP hydrolysis promoted by the dinuclear complex (T = 298 K) is 0.95 M(-1) s(-1), which is ca. 47600-fold higher than that of the hydroxide ion catalyzed hydrolysis (k(OH)). Its activity is selective for the phosphodiester, and the hydrolysis was proved to be catalytic. The proposed bifunctional mechanism of the hydrolysis includes double Lewis acid activation and intramolecular nucleophilic catalysis.

Longitudinally detected EPR: improved instrumentation and new pulse schemes.

A new setup for longitudinal detection (LOD) of EPR signals based on a commercial pulse EPR spectrometer equipped with an ENDOR probehead is presented. The design is suited for pulse LOD EPR and amplitude-modulated cw LOD EPR experiments. The sensitivity is substantially increased compared with earlier designs. Two new pulse schemes that take full advantage of the special properties of the setup are invented. In transient-nutation longitudinally detected EPR (TN-LOD EPR), the nutation of magnetization during a microwave pulse is used to measure the EPR signal. In pulse-train excited longitudinally detected EPR (PT-LOD EPR), a train of microwave pulses that periodically inverts the magnetization is applied. First experimental results on radicals and metal complexes at room temperature are presented.