Current practices used for the prevention of central venous catheter-associated infection in hematopoietic stem cell transplantation recipients: a survey from the Infectious Diseases Working Party and Nurses' Group of EBMT.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) is one of the most common infectious complications after hematopoietic stem cell transplantation. To prevent this complication, international guidelines recommend the implementation of the CLABSI 'prevention bundle' consisting of hand hygiene, full barrier precautions, cleaning the insertion site with chlorhexidine, avoiding femoral sites for insertion, and removing unnecessary catheters. The aim of this survey was to analyze to what extent European Group for Blood and Marrow Transplantation (EBMT) centers have included the CLABSI prevention bundle in practice. METHODS: A questionnaire used for data collection was sent to the 545 EBMT centers worldwide, 103 of which responded. RESULTS: All 5 components of the CLABSI prevention bundle were recorded in 28% of the centers' standard operating procedures (SOP), and 21% of the centers answered that they used all of the bundle components in clinical practice. The most common recommendation absent from the SOP was specification of all the components of full barrier precautions (43% of the centers did not include at least 1 component). Skin disinfection with chlorhexidine before catheter insertion was reported by 66% centers. CLABSI rates were monitored in 21% of centers. CONCLUSIONS: Although most of the centers lacked 1 or more of the CLABSI prevention bundle components in their SOP, improvements could easily be made by updating the centers' SOP. The first important step is introduction of CLABSI rate monitoring in this high-risk patient population.

Separation of time-resolved phenomena in surface-enhanced Raman scattering of the photocatalytic reduction of p-nitrothiophenol.

Straightforward analysis of chemical processes on the nanoscale is difficult, as the measurement volume is linked to a discrete number of molecules, ruling out any ensemble averaging over rotation and diffusion processes. Raman spectroscopy is sufficiently selective for monitoring chemical changes, but is not sufficiently sensitive to be applied directly. Surface-enhanced Raman spectroscopy (SERS) can be applied for studying reaction kinetics, but adds additional variability in the signal as the enhancement factor is not the same for every location. A novel chemometric method described here separates reaction kinetics from short-term variability, based on the lack of fit in a principal-component analysis. We show that it is possible to study effects that occur on different time scales independently without data reduction using the photocatalytic reduction of p-nitrothiophenol as a showcase system. Using this approach a better description of the nanoscale reaction kinetics becomes available, while the short-term variations can be examined separately to examine reorientation and/or diffusion effects. It may even be possible to identify reaction intermediates through this approach. With only a limited number of reactive molecules in the studied volume, an intermediate on a SERS hot spot may temporarily dominate the spectrum. Now such events can be easily separated from the bulk conversion process by making use of this chemometric method.

Opto-mechanical probe for combining atomic force microscopy and optical near-field surface analysis.

We have developed a new easy-to-use probe that can be used to combine atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM). We show that, using this device, the evanescent field, obtained by total internal reflection conditions in a prism, can be visualized by approaching the surface with the scanning tip. Furthermore, we were able to obtain simultaneous AFM and SNOM images of a standard test grating in air and in liquid. The lateral resolution in AFM and SNOM mode was estimated to be 45 and 160 nm, respectively. This new probe overcomes a number of limitations that commercial probes have, while yielding the same resolution.

Factors influencing long-term adherence to two previously implemented hospital guidelines.

OBJECTIVE AND SETTING: After successful implementation, adherence to hospital guidelines should be sustained. Long-term adherence to two hospital guidelines was audited. The overall aim was to explore factors accounting for their long-term adherence or non-adherence. DESIGN AND PARTICIPANTS: A fluid balance guideline (FBG) and body temperature guideline (BTG) were developed and implemented in our hospital in 2000. Long-term adherence was determined retrospectively based on data from patient files. Focus groups were launched to explore nurses' perceptions of barriers and facilitators regarding long-term adherence. The predominant themes from the nurses' focus groups were posed to clinicians in questionnaires. RESULTS: Nurses involved in the FBG (overall adherence 100%) stated that adherence has immediate advantages in terms of safety and a gain in time. Nurses and oncologists acted unanimously which was thought to enhance adherence. On the other hand, opinions differed on the BTG within the nursing teams and medical staff (overall adherence 50%). Although the guideline discourages routine postoperative body temperature measurements, temperature should be measured according to the guideline in a considerable number of cases due to changes in patient characteristics since the year 2000. Therefore, adherence was judged to be rather complex. CONCLUSIONS: To secure adherence to hospital guidelines after their successful implementation, guidelines should preferably be comprehensive in terms of being applicable to the majority of the patients in that particular setting and to the most common clinical situations. All healthcare professionals involved should be aware of its immediate benefits for themselves or to their patients.

Management of related donor care: a European survey.

Donating BM or peripheral stem cells is a challenging process that requires a considerable commitment on the part of the donating individual, especially when there is a relationship between donor and recipient. In order to develop a better understanding of related donor management, the research subcommittee of the European Group for Blood and Marrow Transplantation-Nurses Group (EBMT-NG) designed a questionnaire to survey European transplant centres. This questionnaire investigated several key areas, including guidelines, patient information, donor consent and follow-up services. It was distributed to a sample of delegates (N=150) at the 2005 meeting of the EBMT-NG. Guidelines for the information given to patients were primarily from local (33, 52%), and a combination of local and national (13, 21%) sources. Transplant information was predominantly given to related donors by the recipient's transplant team (36, 57%). A total of 33 (52%) centres indicated that donors were also consented by transplant doctors, whereas 16 (25%) identified that consent was obtained by doctors who were not connected with the transplant team. At present, there is a lack of recognized standardized guidelines for the management of related donors. The development of such guidelines would assist in maintaining patient autonomy, confidentiality and access to accurate and objective information.

An interactive CD-ROM to inform patients about stem cell transplantation.

OBJECTIVE: Cancer patients receiving chemotherapy or a Stem Cell Transplantation (SCT) are in need of information about their disease, treatment options and side effects. Patient education usually has to be given within limited time. Under these circumstances, patients may find it difficult to completely understand and to retain the information given. METHODS: As a supplement to standard information methods we developed an interactive CD-ROM with information on SCT. This CD-ROM provides both medical information and more subjective patients' experiences. Part one provides information regarding the treatment course from diagnosis through to post-discharge care. The second part consists of interviews with former patients and describes their experiences. As the system is interactive, it can be utilised according to the patient's individual preferences. The CD-ROM comprises audio, video, animations, pictures, and text. Printing of certain sections is optional. The technical format of the CD-ROM makes it relatively simple to utilise the information and to make it suitable for other institutions or even other treatments. In this preliminary study the acceptability of the interactive CD-ROM by patients undergoing a SCT is described. RESULTS: Patients' overall evaluations of the interactive CD-ROM were highly positive. For example, 90.2% (N=51) found it interesting, clear, useful and valued getting information by means of a CD-ROM. Most patients would recommend the interactive CD-ROM to other patients in the same situation. CONCLUSION: The content of the CD-ROM on SCT as well as the computer-based interactive method are well accepted by patients. PRACTICE IMPLICATIONS: Computer-based education may enhance patient education and thus the quality of patient care. We must now establish the program's effectiveness. Moreover, plans have been developed to disseminate the information on SCT over the Internet. Future development of comparable programs and their evaluation should be encouraged to promote the well-being of cancer patients.

Confocal Raman microscopy of liquid-crystal-filled polymer capsules made by photo-enforced stratification.

The applicability of confocal Raman microscopy for characterizing thin liquid-crystal (LC) filled polymer capsules obtained by photo-enforced stratification is demonstrated. The investigated structure consists of an array of polymer capsules (typical size 500 x 500 x 20 microm) filled with LC material and is made by photopolymerization of a mixture of monomers and LC. Such an array can be used as the electro-optical component in liquid crystal displays. Confocal Raman microscopy does not require complex sample preparation, is non-invasive, and is shown to have adequate spatial and depth resolution. Although Raman spectroscopy is inherently insensitive, the use of data preprocessing and computational modeling makes it possible to quantify both the conversion of monomer to polymer and the compositions of both the polymer-rich and the LC-rich phase.

In situ Raman analysis of gas formation in NiMH batteries.

In this paper Raman spectrometry is introduced in the field of sealed battery research for in situ gas-phase analysis and for longterm measurements. For this purpose, a new method was successfully applied in order to model battery behavior without interfering with operation. It is shown that oxygen, hydrogen, and nitrogen are responsible for the pressure increase that occurs during overcharging. The relative contribution of the different gases depends on the current imposed on the battery as well as the operating temperature. Reproducible and stable signals could be obtained even under severe conditions such as high pressure and elevated temperature. Oxygen and hydrogen are produced in side reactions taking place during battery operation. However, as nitrogen is unlikely to be a reacting gas inside the battery, the change in its partial pressure can be attributed to electrode expansion and a change in the electrolyte volume.

Monitoring hyperhydration during high-dose chemotherapy: body weight or fluid balance?

Body weight and fluid input/output are usually monitored for checking fluid balance in case of intravenous hyperhydration during nephrotoxic chemotherapy. The reliability of measuring fluid input/output is uncertain. Moreover, this measurement is redundant, complex, labour-intensive and represents an occupational hazard for nurses and other health-care workers handling fluids or body excreta. In a prospective cohort study, we determined the concordance between body weight and fluid intake/output. We also examined the clinical consequences with respect to the safety of selecting only body weight measurement as a parameter for fluid overload. A total of 591 combined observations of fluid balances and body weights were collected. We observed a higher increase in body weight than in fluid balance. The Pearson correlation between fluid balance and body weight was relatively low (r = 0.28). With regard to the safety of measuring body weight only, we found 4 cases (0.6%) who might not have received furosemide if the fluid input/output had not been measured, without clinical consequences, however. After standardization, body weight can safely be used as the only parameter for monitoring fluid retention in case of hyperhydration during chemotherapy.

A genetic linkage map of Guinea yam ( Dioscorea rotundata Poir.) based on AFLP markers.

A genetic linkage map of the tetraploid white yam ( Dioscorea rotundata Poir.) was constructed based on 341 co-dominantly scored amplified fragment length polymorphism (AFLP) markers segregating in an intraspecific F(1) cross. The F(1) mapping population was produced by crossing a landrace cultivar TDr 93-1 as female parent to a breeding line TDr 87/00211 as the male parent. The marker segregation data were split into maternal and paternal data sets, and separate genetic linkage maps were constructed since the mapping population was an F(1) cross between two presumed heterozygous parents. The markers segregated like a diploid cross-pollinator population suggesting that the D. rotundata genome is an allo-tetraploid (2n = 4 x = 40). The maternal map comprised 155 markers mapped on 12 linkage groups with a total map length of 891 cM. Three linkage groups consisted of maternal parent markers only. The paternal map consisted of 157 markers mapped on 13 linkage groups with a total map length of 852 cM. Three and one quantitative trait loci (QTLs) with effects on resistance to Yam Mosaic Virus (YMV) were identified on the maternal and paternal linkage maps, respectively. Prospects for detecting more QTLs and using marker-assisted selection in white yam breeding appear good, but this is subject to the identification of additional molecular markers to cover more of the genome.

A genetic linkage map of water yam ( Dioscorea alata L.) based on AFLP markers and QTL analysis for anthracnose resistance.

A genetic linkage map of the tetraploid water yam ( Dioscorea alata L.) genome was constructed based on 469 co-dominantly scored amplified fragment length polymorphism (AFLP) markers segregating in an intraspecific F(1) cross. The F(1) was obtained by crossing two improved breeding lines, TDa 95/00328 as female parent and TDa 87/01091 as male parent. Since the mapping population was an F(1) cross between presumed heterozygous parents, marker segregation data from both parents were initially split into maternal and paternal data sets, and separate genetic linkage maps were constructed. Later, data analysis showed that this was not necessary and thus the combined markers from both parents were used to construct a genetic linkage map. The 469 markers were mapped on 20 linkage groups with a total map length of 1,233 cM and a mean marker spacing of 2.62 cM. The markers segregated like a diploid cross-pollinator population suggesting that the water yam genome is allo-tetraploid (2n = 4 x = 40). QTL mapping revealed one AFLP marker E-14/M52-307 located on linkage group 2 that was associated with anthracnose resistance, explaining 10% of the total phenotypic variance. This map covers 65% of the yam genome and is the first linkage map reported for D. alata. The map provides a tool for further genetic analysis of traits of agronomic importance and for using marker-assisted selection in D. alata breeding programmes. QTL mapping opens new avenues for accumulating anthracnose resistance genes in preferred D. alata cultivars.

Distribution of aluminum phthalocyanine disulfonate in an oral squamous cell carcinoma model. In vivo fluorescence imaging compared with ex vivo analytical methods.

Photosensitizer-induced fluorescence is studied as a technique for the detection of cancer. Therefore we investigated the ability of a photosensitizer, aluminum phthalocyanine disulfonate (AIPcS2), to localize in tumor tissue. In vivo endoscopic fluorescence imaging, fluorescence microscopy, conventional spectrofluorometry and high performance liquid chromatograpy combined with diode laser-induced fluorescence (HPLC-Dio-LIF) were used. Squamous cell carcinomas were induced with 4-nitro-quinoline-1-oxide (4NQO) in the mucosa of the palate of the rat. In vivo fluorescence images, taken after injection of 1.5 mumol/kg AIPcS2 intravenously, showed that 4NQO-treated palates had higher fluorescence signals than normal palates. Areas displaying locally high amounts of AIPcS2 fluorescence (hot spots) were present only in 4NQO-treated rats 2-8 h but had disappeared 24 h after injection. However, HPLC-Dio-LIF showed that the relative AIPcS2 content was highest at 24/48 h in biopsies taken in the areas of the hot spots. Fluorescence microscopy revealed that AIPcS2 was present only between 2 and 8 h in the epithelial layer, while in biopsies the connective tissue contained large quantities of AIPcS2 at 24/48 h. In vivo fluorescence imaging appears to show mainly fluorescence from the epithelial layer and the ex vivo analytical techniques mainly show the connective tissue fluorescence. Care should be taken when interpreting data using one technique only.

Diode laser-induced fluorescence detection in capillary electrophoresis after pre-column derivatization of amino acids and small peptides.

The use of diode laser-induced fluorescence (DIO-LIF) detection in the field of capillary electrophoresis (CE) is examined. A simple but sensitive detection system was constructed. The performance of the system was evaluated with respect to design factors and its sensitivity was compared with the theoretically achievable sensitivity. To enhance the applicability of direct DIO-LIF detection in CE, a derivatization method for amines was developed. A red-absorbing label, consisting of a dicarbocyanine fluorophore with a succinimidyl ester functionality, was synthesized for this purpose. After derivatization of 1 x 10(-6) M glycine, a detection limit of 0.1 amol was observed for the labeled glycine. Similar detection limits were observed for other amino acids. To show that derivatization preserves the separation efficiency of CE for the analytes examined, 18 amino acids and tyramine were separated with micellar electrokinetic chromatography after labeling. In addition, even labeled peptides, including structurally related enkephalin-type compounds, were separated from each other with zone electrophoresis. To test the applicability of the derivatization method to biological samples, tyramine was determined in urine before and after the consumption of cheese.

Determination of the anticancer drug metabolite WR1065 using pre-column derivatization and diode laser induced fluorescence detection.

A liquid chromatographic (LC) procedure using alumina as stationary phase in both the pre- and the analytical column, is reported for the determination of WR1065, the active metabolite of the amino- and thiol-containing anticancer drug WR2721. After pre-column derivatization of the thiol group, the analyte is determined by LC with diode laser induced fluorescence detection in the near-infrared. Selective removal of excess label is achieved by means of column switching; it allows the detection of 5 x 10(-9) M WR1065 in water and 10-fold diluted, deproteinated plasma samples. The detection limit is determined by the derivatization reaction and not by the fluorescence detection of the labelled analyte. Endogeneous thiols do not interfere.

Growth and biochemical effects of unsymmetrically substituted polyamine analogues in human lung tumor cells 1.

Three unsymmetrically substituted polyamine analogues demonstrate significant and selective antitumor effects. Each of the analogues N1-ethyl-N11-propargyl-4,8-diazaundecane (PENSpm), N1-ethyl-N11-(cyclobutyl)methyl-4,8-diazaundecane (CBENSpm), and N1-ethyl-N11-(cyclopropyl)methyl-4,8-diazaundecane (CPENSpm) is cytotoxic to a representative non-small-cell lung carcinoma line, NCI H157, while being only growth-inhibitory to a representative small-cell-lung carcinoma line, NCI H82. Cytotoxicity is accompanied by a significant increase in expression of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) at the levels of activity and steady-state mRNA. These new analogues are significant both for their cell-type-specific activity and as synthetic prototypes for the addition of SSAT-activated functional groups.

Synthesis and evaluation of unsymmetrically substituted polyamine analogues as modulators of human spermidine/spermine-N1-acetyltransferase (SSAT) and as potential antitumor agents.

Spermidine/spermine-N1-acetyltransferase (SSAT), the rate-limiting step in polyamine catabolism, is critical for the interconversion and modulation of cellular polyamines. Inhibitor-initiated induction of this enzyme also appears to correlate with the sensitivity of tumor cells to a class of novel polyamine analogues, the bis(ethyl)polyamines. Thus, terminally alkylated polyamines which modulate the cellular level of SSAT could be of great value for understanding the role of this enzyme both in analogue-mediated cytotoxicity and in overall cellular polyamine metabolism. Such analogues could also become important therapeutic agents by disrupting cellular polyamine metabolism. The structure-activity relationships defining the interaction of polyamine analogues with SSAT have not been fully elucidated, and, in particular, unsymmetrically alkylated polyamines have not been synthesized and evaluated as modulators of SSAT. To this end, we now report the synthesis and preliminary biological evaluation of N1-ethyl-N11-propargyl-4,8-diazaundecane and N1-ethyl-N11-((cyclopropyl)methyl)-4,8-diazaundecane via a synthetic pathway which represents an efficient route to a variety of unsymmetrically substituted polyamine analogues. The title compounds act as effective inhibitors of isolated human SSAT and produce a differential superinduction of SSAT in situ which appears to be associated with a cell specific cytotoxic response in two human lung cancer cell lines. In so doing, these analogues exhibit promising antitumor activity against cultured human lung cancer cells.

Growth inhibition of hormone-responsive and -resistant human breast cancer cells in culture by N1, N12-bis(ethyl)spermine.

Previous studies have documented differential sensitivity of human lung cancer and melanoma cell lines to the cytotoxic effects of N1, N12-bis(ethyl)spermine (BESpm). We show here that BESpm can significantly inhibit the growth of six human breast cancer cell lines with 50% inhibitory concentration in the microM range. The degree of inhibition does not correlate with estrogen receptor status. Detailed studies with estrogen receptor-positive MCF-7 and estrogen receptor- negative Hs578t cells show a similar dose-response curve with concentrations of 1-10 microM resulting in maximal growth inhibition. Growth inhibition in both lines is associated with an 8-12-fold induction of the polyamine catabolic enzyme, spermidine/spermine N1-acetyltransferase, and a progressive decrease in intracellular polyamine levels over 6 days even though steady-state levels of BESpm are achieved within 24 h. Similar studies on WTMCF7 and AdrRMCF7 cells show that the acquisition of resistance to hormonal or doxorubicin therapy is not associated with resistance to the growth-inhibitory effects of BESpm. These results suggest that BESpm exerts similar growth-inhibitory effects against both hormone-responsive and -unresponsive human breast cancer cells, a finding which has significance for the potential use of polyamine analogues in treating human breast cancer.