bluuebunny/crossref_metadata_2025 huggingface dataset:
Explicit criteria for prioritization of cataract surgery
Authors: M Quintana José , Escobar Antonio , Bilbao Amaia ,   the IRYSS-Appropriateness Cataract Group
Published: March 2006

Background

Consensus techniques have been used previously to create explicit criteria to prioritize cataract extraction; however, the appropriateness of the intervention was not included explicitly in previous studies. We developed a prioritization tool for cataract extraction according to the RAND method.

Methods

Criteria were developed using a modified Delphi panel judgment process. A panel of 11 ophthalmologists was assembled. Ratings were analyzed regarding the level of agreement among panelists. We studied the effect of all variables on the final panel score using general linear and logistic regression models. Priority scoring systems were developed by means of optimal scaling and general linear models. The explicit criteria developed were summarized by means of regression tree analysis.

Results

Eight variables were considered to create the indications. Of the 310 indications that the panel evaluated, 22.6% were considered high priority, 52.3% intermediate priority, and 25.2% low priority. Agreement was reached for 31.9% of the indications and disagreement for 0.3%. Logistic regression and general linear models showed that the preoperative visual acuity of the cataractous eye, visual function, and anticipated visual acuity postoperatively were the most influential variables. Alternative and simple scoring systems were obtained by optimal scaling and general linear models where the previous variables were also the most important. The decision tree also shows the importance of the previous variables and the appropriateness of the intervention.

Conclusion

Our results showed acceptable validity as an evaluation and management tool for prioritizing cataract extraction. It also provides easy algorithms for use in clinical practice.
Use of private gynaecologist does not relate to better prevention outcomes – An ecological analysis from Finland
Authors: Hemminki Elina , Sevon Tiina , Tanninen Kati , Pukkala Eero , Anttila Ahti
Published: March 2006

Background

Control of reproduction and prevention of reproductive health problems are important reasons for women to use health services, but the proper organisational level of service provision is not clear. The purpose of this study was to investigate whether visits to private gynaecologists correlate with better health outcomes and worse participation in organised screening for cancer programs.

Methods

This is an ecological analysis using municipalities and groups of women at 5-year age intervals within municipalities as study units. First, the Finnish municipalities (n = 452) were classified into three groups by the age-adjusted level of use of private gynaecologists. Secondly, each age group within municipalities was classified into tertiles by the level of private gynaecologist use. The outcomes were participation in cervical and organised breast cancer screening for cancer programmes, stage of gynaecological and breast cancers at diagnosis, and abortion rates and ratios. All data were obtained from national registers by groups at 5-year age intervals and by municipality. Raw and adjusted (age groups, and in some analyses, municipality social class index) odds ratios, total and by urbanity, were calculated.

Results

The proportions of women participating in cervical cancer and organised breast cancer screening for cancer were somewhat higher in the groups having a low use of private gynaecologists. The proportions of local cancers of all cervical, uterine, ovarian and breast cancers were similar in the three groups, even though the first analysis method suggested somewhat better results for the low-use group in case of cervical cancer and for the high-use group in case of uterine and breast cancer. The rates of induced abortion were higher in municipalities having a high use of private gynaecologists than in those having lower use.

Conclusion

This ecological analysis suggests that frequent use of private gynaecologists relates somewhat to lower organised screening for cancer participation, and is not better in preventing abortions or in detecting cancer earlier. Our results suggest that a planned system relying mainly on general practitioners and public health nurses as the first line care providers is equally good for women's reproductive health as that in which specialists are used.
Colocalization of somatostatin receptors and epidermal growth factor receptors in breast cancer cells
Authors: Watt Heather L , Kumar Ujendra
Published: March 2006

Background

Somatostatin receptor (SSTR) expression is positively correlated with tumor size and inversely correlated with epidermal growth factor receptor (ErbB) levels and tumor differentiation. In the present study, we compared SSTR1-5 and ErbB1-4 mRNA and protein expression in two breast cancer cell lines: MCF-7 (ER+) and MDA-MB-231 (ERα-).

Results

All five SSTRs and four ErbBs were variably expressed as both cell surface and cytoplasmic proteins. In both cell lines, SSTR4 and SSTR1 were highly expressed, followed by SSTR2 and SSTR5 with SSTR3 being the least expressed subtype, at the protein level. ErbBs were variably expressed with ErbB1 as the predominant subtype in both cell lines. ErbB1 is followed by ErbB3, ErbB2 and ErbB4 in MCF-7 at both the protein and mRNA levels. In MDA-MB-231 cells, ErbB1 is followed by ErbB2, ErbB4 and ErbB3. Our results indicate significant correlations at the level of mRNA and protein expression in a cell and receptor-specific manner. Using indirect immunofluorescence, we found that, in MCF-7 cells, SSTR5 was the most prominent subtype coexpressed with ErbBs followed by SSTR3, SSTR4, SSTR1 and SSTR2, respectively. In MDA-MB-231 cells, SSTR1 colocalized strongly with ErbBs followed by SSTR5, SSTR4, SSTR3 and SSTR2. ErbBs displayed higher levels of colocalization amongst themselves in MCF-7 cells than in MDA-MB-231 cells.

Conclusion

These findings may explain the poor response to endocrine therapy in ER-cancer. Differential distribution of SSTR subtypes with ErbBs in breast cancer cells in a receptor-specific manner may be considered as a novel diagnosis for breast tumors.
Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway
Authors: Datta Milton W , Hernandez Ana Maria , Schlicht Michael J , Kahler Andrea J , DeGueme Amy M , Dhir Rajiv , Shah Rajal B , Farach-Carson Cindy , Barrett Andrea , Datta Sumana
Published: March 2006

Background

Genetic studies associated the CAPB locus with familial risk of brain and prostate cancers. We have identified HSPG2 (Perlecan) as a candidate gene for CAPB. Previously we have linked Perlecan to Hedgehog signaling in Drosophila. More recently, we have demonstrated the importance of Hedgehog signaling in humans for advanced prostate cancer.

Results

Here we demonstrate Perlecan expression in prostate cancer, and its function in prostate cancer cell growth through interaction and modulation of Sonic Hedgehog (SHH) signaling. Perlecan expression in prostate cancer tissues correlates with a high Gleason score and rapid cell proliferation. Perlecan is highly expressed in prostate cancer cell lines, including androgen insensitive cell lines and cell lines selected for metastatic properties. Inhibition of Perlecan expression in these cell lines decreases cell growth. Simultaneous blockade of Perlecan expression and androgen signaling in the androgen-sensitive cell line LNCaP was additive, indicating the independence of these two pathways. Perlecan expression correlates with SHH in tumor tissue microarrays and increased tumor cell proliferation based on Ki-67 immunohistochemistry. Inhibition of Perlecan expression by siRNA in prostate cancer cell lines decreases SHH signaling while expression of the downstream SHH effector GLI1 rescues the proliferation defect. Perlecan forms complexes with increasing amounts of SHH that correlate with increasing metastatic potential of the prostate cancer cell line. SHH signaling also increases in the more metastatic cell lines. Metastatic prostate cancer cell lines grown under serum-starved conditions (low androgen and growth factors) resulted in maintenance of Perlecan expression. Under low androgen, low growth factor conditions, Perlecan expression level correlates with the ability of the cells to maintain SHH signaling.

Conclusion

We have demonstrated that Perlecan, a candidate gene for the CAPB locus, is a new component of the SHH pathway in prostate tumors and works independently of androgen signaling. In metastatic tumor cells increased SHH signaling correlates with the maintenance of Perlecan expression and more Perlecan-SHH complexes. Perlecan is a proteoglycan that regulates extracellular and stromal accessibility to growth factors such as SHH, thus allowing for the maintenance of SHH signaling under growth factor limiting conditions. This proteoglycan represents an important central regulator of SHH activity and presents an ideal drug target for blocking SHH effects.
Elevated rates of HIV infection among young Aboriginal injection drug users in a Canadian setting
Authors: Miller Cari L , Strathdee Steffanie A , Spittal Patricia M , Kerr Thomas , Li Kathy , Schechter Martin T , Wood Evan
Published: March 2006

Objectives

Recent reports have suggested that Aboriginal and American Indian people are at elevated risk of HIV infection. We undertook the present study to compare socio-demographic and risk variables between Aboriginal and non-Aboriginal young (aged 13 – 24 years) injection drug users (IDUs) and characterize the burden of HIV infection among young Aboriginal IDUs.

Methods

We compared socio-demographic and risk variables between Aboriginal and non-Aboriginal young IDUs. Data were collected through the Vancouver Injection Drug Users Study (VIDUS). Semi-annually, participants have completed an interviewer-administered questionnaire and have undergone serologic testing for HIV and Hepatitis C (HCV).

Results

To date over 1500 Vancouver IDU have been enrolled and followed, among whom 291 were aged 24 years and younger. Of the 291 young injectors, 80 (27%) were Aboriginal. In comparison to non-Aboriginal youth, Aboriginal youth were more likely to test seropositive for either HIV (20% vs 7%, p=< 0.001) or Hepatitis C virus (HCV) (66% vs 38%, p =< 0.001), be involved in sex work and live in the city's IDU epi-centre at baseline. After 48 months of follow-up, Aboriginal youth experienced significantly higher HIV seroconversion rates than non-Aboriginal youth, 27.8 per ppy (95% CI: 13.4–42.2) vs. 7.0 per ppy (95% CI: 2.3–11.8) respectively (log-rank p = 0.005) and the incidence density over the entire follow-up period was 12.6 per 100 pyrs (CI: 6.49–21.96) and 3.9 per 100 pyrs (CI: 1.8–7.3) respectively.

Interpretation

These findings demonstrate that culturally relevant, evidence based prevention programs are urgently required to prevent HIV infection among Aboriginal youth.
Associations between health-related quality of life and demographics and health risks. Results from Rhode Island's 2002 behavioral risk factor survey
Authors: Jiang Yongwen , Hesser Jana Earl
Published: March 2006

Background

Health-Related Quality of Life (HRQOL) has received much attention in recent years. HRQOL indicators have been used to track population trends, identify health disparities, and monitor progress in achieving national health objectives for 2010. Prior studies have examined health risks and HRQOL at the national level as well as at the state level. This paper examines multiple indicators of HRQOL by demographic characteristics and selected health behaviors for Rhode Island adults.

Methods

Data from Rhode Island's 2002 Behavioral Risk Factor Surveillance System (BRFSS), a random digit dialled telephone survey, were used for this study. The state wide sample contained a total of 3,843 respondents ages 18 and older. Multiple Imputation (MI) was applied to handle missing data, and data were modelled for each of 10 HRQOL indicators using multivariable logistic regression.

Results

By examining HRQOL through a multivariable approach we identified the strongest predictors for multiple indicators of poor HRQOL as well as predictors for specific indicators of poor HRQOL. Predictors for multiple indicators of poor HRQOL were: disability, inability to work, unemployment, lower income, lack of exercise, asthma, and smoking (specifically associated with poor mental health).

Conclusion

Using multiple measures of HRQOL can help to assess the burden of poor health in a population, identify subgroups with unmet HRQOL needs, inform the development of targeted interventions, and monitor changes in a population's HRQOL over time. Use of these HRQOL measures in longitudinal and intervention studies is needed to increase our understanding of the causal relationships between demographics, health risk behaviors, and HRQOL.
Hydralazine target: From blood vessels to the epigenome
Authors: Arce Claudia , Segura-Pacheco Blanca , Perez-Cardenas Enrique , Taja-Chayeb Lucia , Candelaria Myrna , Dueñnas-Gonzalez Alfonso
Published: March 2006

Hydralazine was one of the first orally active antihypertensive drugs developed. Currently, it is used principally to treat pregnancy-associated hypertension. Hydralazine causes two types of side effects. The first type is an extension of the pharmacologic effect of the drug and includes headache, nausea, flushing, hypotension, palpitation, tachycardia, dizziness, and salt retention. The second type of side effects is caused by immunologic reactions, of which the drug-induced lupus-like syndrome is the most common, and provides clues to underscoring hydralazine's DNA demethylating property in connection with studies demonstrating the participation of DNA methylation disorders in immune diseases. Abnormalities in DNA methylation have long been associated with cancer. Despite the fact that malignant tumors show global DNA hypomethylation, regional hypermethylation as a means to silence tumor suppressor gene expression has attracted the greatest attention. Reversibility of methylation-induced gene silencing by pharmacologic means, which in turns leads to antitumor effects in experimental and clinical scenarios, has directed efforts toward developing clinically useful demethylating agents. Among these, the most widely used comprise the nucleosides 5-azacytidine and 2'deoxy-5-azacytidine; however, these agents, like current cytotoxic chemotherapy, causes myelosuppression among other side effects that could limit exploitation of their demethylating properties. Among non-nucleoside DNA demethylating drugs currently under development, the oral drug hydralazine possess the ability to reactivate tumor suppressor gene expression, which is silenced by promoter hypermethylationin vitroandin vivo. Decades of extensive hydralazine use for hypertensive disorders that demonstrated hydralazine's clinical safety and tolerability supported its testing in a phase I trial in patients with cancer, confirming its DNA demethylating activity. Hydralazine is currently being evaluated, along with histone deacetylase inhibitors either alone or as adjuncts to chemotherapy and radiation, for hematologic and solid tumors in phase II studies.
Alternating ibuprofen and acetaminophen in the treatment of febrile children: a pilot study [ISRCTN30487061]
Authors: Nabulsi Mona M , Tamim Hala , Mahfoud Ziyad , Itani Mohammad , Sabra Ramzi , Chamseddine Fadi , Mikati Mohammad
Published: March 2006

Background

Alternating ibuprofen and acetaminophen for the treatment of febrile children is a prevalent practice among physicians and parents, despite the lack of evidence on effectiveness or safety. This randomized, double-blind and placebo-controlled clinical trial aims at comparing the antipyretic effectiveness and safety of a single administration of alternating ibuprofen and acetaminophen doses to that of ibuprofen mono-therapy in febrile children.

Methods

Seventy febrile children were randomly allocated to receive either a single oral dose of 10 mg/kg ibuprofen and 15 mg/kg oral acetaminophen after 4 hours, or a similar dose of ibuprofen and placebo at 4 hours. Rectal temperature was measured at baseline, 4, 5, 6, 7 and 8 hours later. Endpoints included proportions of afebrile children at 6, 7 and 8 hours, maximum decline in temperature, time to recurrence of fever, and change in temperature from baseline at each time point. Intent-to-treat analysis was planned with statistical significance set at P < 0.05.

Results

A higher proportion of subjects in the intervention group (83.3%) became afebrile at 6 hours than in the control group (57.6%); P = 0.018. This difference was accentuated at 7 and 8 hours (P < 0.001) with a significantly longer time to recurrence of fever in the intervention group (mean ± SD of 7.4 ± 1.3 versus 5.7 ± 2.2 hours), P < 0.001. Odds ratios (95%CI) for defervescence were 5.6 (1.3; 23.8), 19.5 (3.5; 108.9) and 15.3 (3.4; 68.3) at 6, 7 and 8 hours respectively. Two-way ANOVA with repeated measures over time revealed a significantly larger decline in temperature in the intervention group at times 7 (P = 0.026) and 8 (P = 0.002) hours.

Conclusion

A single dose of alternating ibuprofen and acetaminophen appears to be a superior antipyretic regimen than ibuprofen mono-therapy. Further studies are needed to confirm these findings.
HTLV-I antisense transcripts initiating in the 3'LTR are alternatively spliced and polyadenylated
Authors: Cavanagh Marie-Hélène , Landry Sébastien , Audet Brigitte , Arpin-André Charlotte , Hivin Patrick , Paré Marie-Ève , Thête Julien , Wattel Éric , Marriott Susan J , Mesnard Jean-Michel , Barbeau Benoit
Published: March 2006

Background

Antisense transcription in retroviruses has been suggested for both HIV-1 and HTLV-I, although the existence and coding potential of these transcripts remain controversial. Thorough characterization is required to demonstrate the existence of these transcripts and gain insight into their role in retrovirus biology.

Results

This report provides the first complete characterization of an antisense retroviral transcript that encodes the previously described HTLV-I HBZ protein. In this study, we show that HBZ-encoding transcripts initiate in the 3' long terminal repeat (LTR) at several positions and consist of two alternatively spliced variants (SP1 and SP2). Expression of the most abundant HBZ spliced variant (SP1) could be detected in different HTLV-I-infected cell lines and importantly in cellular clones isolated from HTLV-I-infected patients. Polyadenylation of HBZ RNA occurred at a distance of 1450 nucleotides downstream of the HBZ stop codon in close proximity of a typical polyA signal. We have also determined that translation mostly initiates from the first exon located in the 3' LTR and that the HBZ isoform produced from the SP1 spliced variant demonstrated inhibition of Tax and c-Jun-dependent transcriptional activation.

Conclusion

These results conclusively demonstrate the existence of antisense transcription in retroviruses, which likely plays a role in HTLV-I-associated pathogenesis through HBZ protein synthesis.
Comparative analysis of follicle morphology and oocyte diameter in four mammalian species (mouse, hamster, pig, and human)
Authors: Griffin Jeanine , Emery Benjamin R , Huang Ivan , Peterson C Matthew , Carrell Douglas T
Published: March 2006

Background

Laboratory animals are commonly used for evaluating the physiological properties of the mammalian ovarian follicle and the enclosed oocyte. The use of different species to determine the morphological relationship between the follicle and oocyte has led to a recognizable pattern of follicular stages, but differences in follicle size, oocyte diameter and granulosa cell proliferation are not consistent across the different species. In an effort to better understand how these differences are expressed across multiple species, this investigation evaluates oocyte and follicle diameters and granulosa cell proliferation in the mouse, hamster, pig, and human.

Methods

Histological sections of ovaries from the mouse, hamster, pig, and human were used to calculate the diameter of the oocyte and follicle and the number of granulosa cells present at pre-determined stages of follicular development. A statistical analysis of these data was performed to determine the relationship of follicular growth and development within and between the species tested.

Results

These data have revealed that the relationships of the features listed are tightly regulated within each species, but they vary between the species studied.

Conclusion

This information may be useful for comparative studies conducted in different animal models and the human.
A phosphorylation map of the bovine papillomavirus E1 helicase
Authors: Lentz Michael R , Stevens Stanley M , Raynes Joshua , Elkhoury Nancy
Published: March 2006

Background

Papillomaviruses undergo a complex life cycle requiring regulated DNA replication. The papillomavirus E1 helicase is essential for viral DNA replication and plays a key role in controlling viral genome copy number. The E1 helicase is regulated at least in part by protein phosphorylation, however no systematic approach to phosphate site mapping has been attempted. We have utilized mass spectrometry of purified bovine papillomavirus E1 protein to identify and characterize new sites of phosphorylation.

Results

Mass spectrometry andin silicosequence analysis were used to identify phosphate sites on the BPV E1 protein and kinases that may recognize these sites. Five new and two previously known phosphorylation sites were identified. A phosphate site map was created and used to develop a general model for the role of phosphorylation in E1 function.

Conclusion

Mass spectrometric analysis identified seven phosphorylated amino acids on the BPV E1 protein. Taken with three previously identified sites, there are at least ten phosphoamino acids on BPV E1. A number of kinases were identified by sequence analysis that could potentially phosphorylate E1 at the identified positions. Several of these kinases have known roles in regulating cell cycle progression. A BPV E1 phosphate map and a discussion of the possible role of phosphorylation in E1 function are presented.
Head repositioning errors in normal student volunteers: a possible tool to assess the neck's neuromuscular system
Authors: Owens Edward F , Henderson Charles NR , Gudavalli M Ram , Pickar Joel G
Published: March 2006

Background

A challenge for practitioners using spinal manipulation is identifying when an intervention is required. It has been recognized that joint pain can interfere with the ability to position body parts accurately and that the recent history of muscle contraction can play a part in that interference. In this study, we tested whether repositioning errors could be induced in a normal population by contraction or shortening of the neck muscles.

Methods

In the experimental protocol, volunteers free of neck problems first found a comfortable neutral head posture with eyes closed. They deconditioned their cervical muscles by moving their heads 5 times in either flexion/extension or lateral flexion and then attempted to return to the same starting position. Two conditioning sequences were interspersed within the task: hold the head in an extended or laterally flexed position for 10 seconds; or hold a 70% maximum voluntary contraction in the same position for 10 seconds. A computer-interfaced electrogoniometer was used to measure head position while a force transducer coupled to an auditory alarm signaled the force of isometric contraction. The difference between the initial and final head orientation was calculated in 3 orthogonal planes. Analysis of variance (1-way ANOVA) with a blocking factor (participants) was used to detect differences in proprioceptive error among the conditioning sequences while controlling for variation between participants.

Results

Forty-eight chiropractic students participated: 36 males and 12 females, aged 28.2 ± 4.8 yrs. During the neck extension test, actively contracting the posterior neck muscles evoked an undershoot of the target position by 2.1° (p <0.001). No differences in repositioning were found during the lateral flexion test.

Conclusion

The results suggest that the recent history of cervical paraspinal muscle contraction can influence head repositioning in flexion/extension. To our knowledge this is the first time that muscle mechanical history has been shown to influence proprioceptive accuracy in the necks of humans. This finding may be used to elucidate the mechanism behind repositioning errors seen in people with neck pain and could guide development of a clinical test for involvement of paraspinal muscles in cervical pain and dysfunction.
Reliability of the Hazelbaker Assessment Tool for Lingual Frenulum Function
Authors: Amir Lisa H , James Jennifer P , Donath Susan M
Published: March 2006

Background

About 3% of infants are born with a tongue-tie which may lead to breastfeeding problems such as ineffective latch, painful attachment or poor weight gain. The Hazelbaker Assessment Tool for Lingual Frenulum Function (HATLFF) has been developed to give a quantitative assessment of the tongue-tie and recommendation about frenotomy (release of the frenulum). The aim of this study was to assess the inter-rater reliability of the HATLFF.

Methods

Fifty-eight infants referred to the Breastfeeding Education and Support Services (BESS) at The Royal Women's Hospital for assessment of tongue-tie and 25 control infants were assessed by two clinicians independently.

Results

The Appearance items received kappas between about 0.4 to 0.6, which represents "moderate" reliability. The first three Function items (lateralization, lift and extension of tongue) had kappa values over 0.65 which indicates "substantial" agreement. The four Function items relating to infant sucking (spread, cupping, peristalsis and snapback) received low kappa values with insignificant p values. There was 96% agreement between the two assessors on the recommendation for frenotomy (kappa 0.92, excellent agreement). The study found that the Function Score can be more simply assessed using only the first three function items (ie not scoring the sucking items), with a cut-off of ≤4 for recommendation of frenotomy.

Conclusion

We found that the HATLFF has a high reliability in a study of infants with tongue-tie and control infants
Recall of age of weaning and other breastfeeding variables
Authors: Gillespie Brenda , d'Arcy Hannah , Schwartz Kendra , Bobo Janet Kay , Foxman Betsy
Published: March 2006

Background

Many studies of the impact of breastfeeding on child or maternal health have relied on data reported retrospectively. The goal of this study was to assess recall accuracy among breastfeeding mothers of retrospectively collected data on age of weaning, reasons for cessation, breast pain, lactation mastitis, and pumping.

Methods

Women in Michigan and Nebraska, U.S.A. were interviewed by telephone every 3 weeks during the first 3 months after the birth of their child, and mailed a questionnaire at 6 months. A subset was interviewed again by telephone approximately 1–3.5 years after the birth. The results for the three recall periods, collected 1994–1998, were compared using correlation, linear and Cox regression analysis, and sensitivity and specificity estimates.

Results

The 184 participants were aged 18–42, mostly white (95%) and 63% had an older child. The age of weaning tended to be overestimated in interviews 1–3.5 years after birth compared to those within 3 weeks of the event, by approximately one month for 1–3.5 year recall and two weeks for 6-month recall (p < 0.001 in both cases). Recall accuracy of reasons for weaning varied greatly by reason, with mastitis and return to work having the most recall validity. The sensitivity of 1–3.5 year recall of mastitis was 80%, but was only 54% for nipple cracks or sores.

Conclusion

Breastfeeding duration among short-term breastfeeders tended to be somewhat overestimated when measured at 1–3.5 years post-partum. Reporting of other breastfeeding characteristics had variable reliability. Studies employing retrospective breastfeeding data should consider the possibility of such errors.
Intra- and inter-radiation therapist reproducibility of daily isocenter verification using prostatic fiducial markers
Authors: Ullman Karen L , Ning Holly , Susil Robert C , Ayele Asna , Jocelyn Lucresse , Havelos Jan , Guion Peter , Xie Huchen , Li Guang , Arora Barbara C , Cannon Angela , Miller Robert W , Norman Coleman C , Camphausen Kevin , Ménard Cynthia
Published: March 2006

Background

We sought to determine the intra- and inter-radiation therapist reproducibility of a previously established matching technique for daily verification and correction of isocenter position relative to intraprostatic fiducial markers (FM).

Materials and methods

With the patient in the treatment position, anterior-posterior and left lateral electronic images are acquired on an amorphous silicon flat panel electronic portal imaging device. After each portal image is acquired, the therapist manually translates and aligns the fiducial markers in the image to the marker contours on the digitally reconstructed radiograph. The distances between the planned and actual isocenter location is displayed. In order to determine the reproducibility of this technique, four therapists repeated and recorded this operation two separate times on 20 previously acquired portal image datasets from two patients. The data were analyzed to obtain the mean variability in the distances measured between and within observers.

Results

The mean and median intra-observer variability ranged from 0.4 to 0.7 mm and 0.3 to 0.6 mm respectively with a standard deviation of 0.4 to 1.0 mm. Inter-observer results were similar with a mean variability of 0.9 mm, a median of 0.6 mm, and a standard deviation of 0.7 mm. When using a 5 mm threshold, only 0.5% of treatments will undergo a table shift due to intra or inter-observer error, increasing to an error rate of 2.4% if this threshold were reduced to 3 mm.

Conclusion

We have found high reproducibility with a previously established method for daily verification and correction of isocenter position relative to prostatic fiducial markers using electronic portal imaging.
B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed under stimulation by interferon in salivary gland epithelial cells in primary Sjögren's syndrome
Authors: Ittah Marc , Miceli-Richard Corinne , Eric Gottenberg Jacques- , Lavie Frédéric , Lazure Thierry , Ba Nathalie , Sellam Jérémie , Lepajolec Christine , Mariette Xavier
Published: March 2006

B cell-activating factor (BAFF) has a key role in promoting B-lymphocyte activation and survival in primary Sjögren's syndrome (pSS). The cellular origin of BAFF overexpression in salivary glands of patients with pSS is not fully known. We investigated whether salivary gland epithelial cells (SGECs), the main targets of autoimmunity in pSS, could produce and express BAFF. We used quantitative RT-PCR, ELISA and immunocytochemistry in cultured SGECs from eight patients with pSS and eight controls on treatment with IL-10, tumor necrosis factor α (TNF-α), IFN-α and IFN-γ. At baseline, BAFF expression in SGECs was low in pSS patients and in controls. Treatment with IFN-α, IFN-γ and TNF-α + IFN-γ increased the level of BAFF mRNA in pSS patients (the mean increases were 27-fold, 25-fold and 62-fold, respectively) and in controls (mean increases 19.1-fold, 26.7-fold and 17.7-fold, respectively), with no significant difference between patients and controls. However, in comparison with that at baseline, stimulation with IFN-α significantly increased the level of BAFF mRNA in SGECs of pSS patients (p = 0.03) but not in controls (p = 0.2), which suggests that SGECs of patients with pSS are particularly susceptible to expressing BAFF under IFN-α stimulation. Secretion of BAFF protein, undetectable at baseline, was significantly increased after IFN-α and IFN-γ stimulation both in pSS patients (40.8 ± 12.5 (± SEM) and 47.4 ± 18.7 pg/ml, respectively) and controls (24.9 ± 8.0 and 9.0 ± 3.9 pg/ml, respectively), with no significant difference between pSS and controls. Immunocytochemistry confirmed the induction of cytoplasmic BAFF expression after stimulation with IFN-α and IFN-γ. This study confirms the importance of resident cells of target organs in inducing or perpetuating autoimmunity. Demonstrating the capacity of SGECs to express and secrete BAFF after IFN stimulation adds further information to the pivotal role of these epithelial cells in the pathogenesis of pSS, possibly after stimulation by innate immunity. Our results suggest that an anti-BAFF therapeutic approach could be particularly interesting in pSS.
Cutaneous vascular reactivity and flow motion response to vasopressin in advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome
Authors: Luckner Günter , Dünser Martin W , Stadlbauer Karl-Heinz , Mayr Viktoria D , Jochberger Stefan , Wenzel Volker , Ulmer Hanno , Pajk Werner , Hasibeder Walter R , Friesenecker Barbara , Knotzer Hans
Published: March 2006

Introduction

Disturbances in microcirculatory homeostasis have been hypothesized to play a key role in the pathophysiology of multiple organ dysfunction syndrome and vasopressor-associated ischemic skin lesions. The effects of a supplementary arginine vasopressin (AVP) infusion on microcirculation in vasodilatory shock and postoperative multiple organ dysfunction syndrome are unknown.

Method

Included in the study were 18 patients who had undergone cardiac or major surgery and had a mean arterial blood pressure below 65 mmHg, despite infusion of more than 0.5 μg/kg per min norepinephrine. Patients were randomly assigned to receive a combined infusion of AVP/norepinephrine or norepinephrine alone. Demographic and clinical data were recorded at study entry and after 1 hour. A laser Doppler flowmeter was used to measure the cutaneous microcirculatory response at randomization and after 1 hour. Reactive hyperaemia and oscillatory changes in the Doppler signal were measured during the 3 minutes before and after a 5-minute period of forearm ischaemia.

Results

Patients receiving AVP/norepinephrine had a significantly higher mean arterial pressure (P = 0.047) and higher milrinone requirements (P = 0.025) than did the patients who received norepinephrine only at baseline. Mean arterial blood pressure significantly increased (P < 0.001) and norepinephrine requirements significantly decreased (P < 0.001) in the AVP/norepinephrine group. Patients in the AVP/norepinephrine group exhibited a significantly higher oscillation frequency of the Doppler signal before ischaemia and during reperfusion at randomization. During the study period, there were no differences in either cutaneous reactive hyperaemia or the oscillatory pattern of vascular tone between groups.

Conclusion

Supplementary AVP infusion in patients with advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome did not compromise cutaneous reactive hyperaemia and flowmotion when compared with norepinephrine infusion alone.
Fatality after deliberate ingestion of sustained-release ibuprofen: a case report
Authors: Wood David Michael , Monaghan Jane , Streete Peter , Jones Alison Linda , Dargan Paul Ivor
Published: March 2006

Introduction

Ibuprofen is a nonsteroidal anti-inflammatory drug available over the counter and on prescription for the management of pain and inflammation. Severe toxicity is rare following deliberate self-poisoning with ibuprofen, and patients are usually either asymptomatic or develop only mild gastrointestinal toxicity. Although there have been nine other reported fatalities, co-existent factors have probably contributed to all of these deaths. We report here a fatality from isolated toxicity following self-poisoning with sustained-release ibuprofen.

Case report

A 26-year-old female presented after deliberate ingestion of up to 105 g sustained-release ibuprofen, with a reduced level of consciousness, severe metabolic acidosis and haemodynamic compromise. Despite intensive supportive management, gut decontamination with multidose activated charcoal and correction of the metabolic acidosis with sodium bicarbonate and haemofiltration, the patient did not survive. The ibuprofen concentration ante mortem on presentation in peripheral blood was 760 mg/l and the concentrations post mortem were 518 mg/l in peripheral blood, 74 mg/kg in liver extract and 116 mg/l in the gastric contents.

Discussion

Most patients with ibuprofen poisoning are either asymptomatic or have mild gastrointestinal symptoms; severe poisoning with ibuprofen is rare. We report the first death related to isolated sustained-release ibuprofen poisoning.
Peripheral arterial blood pressure monitoring adequately tracks central arterial blood pressure in critically ill patients: an observational study
Authors: Mignini Mariano Alejandro , Piacentini Enrique , Dubin Arnaldo
Published: March 2006

Introduction

Invasive arterial blood pressure monitoring is a common practice in intensive care units (ICUs). Accuracy of invasive blood pressure monitoring is crucial in evaluating the cardiocirculatory system and adjusting drug therapy for hemodynamic support. However, the best site for catheter insertion is controversial. Lack of definitive information in critically ill patients makes it difficult to establish guidelines for daily practice in intensive care. We hypothesize that peripheral and central mean arterial blood pressures are interchangeable in critically ill patients.

Methods

This is a prospective, observational study carried out in a surgical-medical ICU in a teaching hospital. Fifty-five critically ill patients with clinical indication of invasive arterial pressure monitoring were included in the study. No interventions were made. Simultaneous measurements were registered in central (femoral) and peripheral (radial) arteries. Bias and precision between both measurements were calculated with Bland-Altman analysis for the whole group. Bias and precision were compared between patients receiving high doses of vasoactive drugs (norepinephrine or epinephrine >0.1 μg/kg/minute or dopamine >10 μg/kg/minute) and those receiving low doses (norepinephrine or epinephrine <0.1 μg/kg/minute or dopamine <10 μg/kg/minute).

Results

Central mean arterial pressure was 3 ± 4 mmHg higher than peripheral mean arterial pressure for the whole population and there were no differences between groups (3 ± 4 mmHg for both groups).

Conclusion

Measurement of mean arterial blood pressure in radial or femoral arteries is clinically interchangeable. It is not mandatory to cannulate the femoral artery, even in critically ill patients receiving high doses of vasoactive drugs.
Modulation of the transcription regulatory program in yeast cells committed to sporulation
Authors: Friedlander Gilgi , Joseph-Strauss Daphna , Carmi Miri , Zenvirth Drora , Simchen Giora , Barkai Naama
Published: March 2006

Background

Meiosis in budding yeast is coupled to the process of sporulation, where the four haploid nuclei are packaged into a gamete. This differentiation process is characterized by a point of transition, termed commitment, when it becomes independent of the environment. Not much is known about the mechanisms underlying commitment, but it is often assumed that positive feedback loops stabilize the underlying gene-expression cascade.

Results

We describe the gene-expression program of committed cells. Sporulating cells were transferred back to growth medium at different stages of the process, and their transcription response was characterized. Most sporulation-induced genes were immediately downregulated upon transfer, even in committed cells that continued to sporulate. Focusing on the metabolic-related transcription response, we observed that pre-committed cells, as well as mature spores, responded to the transfer to growth medium in essentially the same way that vegetative cells responded to glucose. In contrast, committed cells elicited a dramatically different response.

Conclusion

Our results suggest that cells ensure commitment to sporulation not by stabilizing the process, but by modulating their gene-expression program in an active manner. This unique transcriptional program may optimize sporulation in an environment-specific manner.
Diphenylhydantoin Suppresses Glucose-Induced Insulin Release by Decreasing Cytoplasmic H+ Concentration in Pancreatic Islets
Authors: Nabe Koichiro , Fujimoto Shimpei , Shimodahira Makiko , Kominato Rieko , Nishi Yuichi , Funakoshi Shogo , Mukai Eri , Yamada Yuichiro , Seino Yutaka , Inagaki Nobuya
Published: March 2006

Diphenylhydantoin (DPH), which is clinically used in the treatment of epilepsy, inhibits glucose-induced insulin release from pancreatic islets by a mechanism that remains unknown. In the present study, DPH is shown to suppress glucose-induced insulin release concentration-dependently. In dynamic experiments, 20 μm DPH suppressed 16.7 mm glucose-induced biphasic insulin release. DPH also suppressed insulin release in the presence of 16.7 mm glucose, 200 μm diazoxide, and 30 mm K+ without affecting the intracellular Ca2+ concentration. DPH suppressed ATP content and mitochondrial membrane hyperpolarization in the presence of 16.7 mm glucose without affecting glucose utilization, glucose oxidation, and reduced nicotinamide adenine dinucleotide phosphate fluorescence. DPH increased cytoplasmic pH in the presence of high glucose, but the increase was abolished under Na+-deprived conditions and HCO3−-deprived conditions, suggesting that Na+ and HCO3− transport across the plasma membrane are involved in the increase in cytoplasmic pH by DPH. Alkalization by adding NH4+ to the extracellular medium also suppressed insulin release, ATP content, and mitochondrial membrane hyperpolarization. Because ATP production from the mitochondrial fraction in the presence of substrates was decreased by increased pH in the medium, DPH suppresses mitochondrial ATP production by reducing the H+ gradient across mitochondrial membrane. Using permeabilized islets, the increase in pH was shown to decrease Ca2+ efficacy at a clamped concentration of ATP in the exocytotic system. Taken together, DPH inhibits glucose-induced insulin secretion not only by inhibiting mitochondrial ATP production, but also by reducing Ca2+ efficacy in the exocytotic system through its alkalizing effect on cytoplasm.
Surgical Management of Acute Subdural Hematomas
Authors: Bullock M Ross , Chesnut Randall , Ghajar Jamshid , Gordon David , Hartl Roger , Newell David W. , Servadei Franco , Walters Beverly C. , Wilberger Jack E.
Published: March 2006

Indications for Surgery

Timing

Methods
Surgical Management of Traumatic Parenchymal Lesions
Authors: Bullock M Ross , Chesnut Randall , Ghajar Jamshid , Gordon David , Hartl Roger , Newell David W. , Servadei Franco , Walters Beverly C. , Wilberger Jack
Published: March 2006

RECOMMENDATIONS (see Methodology)

Indications

Timing and Methods
Letter: Some More Aspects of Formation and Stability of the Protonated Serine Octamer Cluster
Authors: Mazurek Ulf
Published: March 2006

The formation of protonated serine octamer clusters from homochiral and heterochiral monomer solutions was investigated. The well-established preference for homochiral cluster formation was found to originate from collision-induced dissociation of the less stable ion population B prior to reaching the mass spectrometer's analyzer cell. In addition, collision-induced dissociation experiments were undertaken to investigate the relative stabilities of populations A and B and infrared multi-photon dissociation experiments addressed the relative stabilities of the protonated serine octamer cluster and its metaclusters. Isotopically-labeled serine was used throughout the experiments.
Letter: Radical Ion and Protonated Molecule Formation with Retinal in Electrospray and Nanospray
Authors: Guaratini Thais , Gates Paul J. , Cardozo Karina H.M. , Campos Patrícia M.B.G.M. , Colepicolo Pio , Lopes Norberto P.
Published: March 2006

This paper reports a preliminary study of the nanospray ionisation mass spectrometry analyses of retinoic acid and retinal. The results are compared and contrasted to the results normally observed with electrospray ionisation. A significant difference in behaviour was observed for the balance between radical ion formation and protonated molecule formation for retinal. The results suggest that the influence of the very different ionisation conditions present in nanospray is very important in determining how ionisation is achieved and has potentially wide ranging applications in the fields of mass spectral analysis of biological and medical extracts.
Attributions and personality as predictors of the road rage response
Authors: Britt Thomas W. , Garrity Michael J.
Published: March 2006

This study examined the ability of attributions and personality traits to predict the emotional and behavioural components of the road rage response. Participants recalled a recent time when they experienced three different anger‐provoking events when driving. They then rated their behaviours and emotions during the event, and their attributions for why the event occurred. Participants also completed a battery of personality questionnaires designed to predict their responses to the situations. Attributing causality for the anger‐arousing event to a stable factor in the offending driver was uniquely related to aggressive behaviour and anger in all three situations. Hostile and blame attributions predicted aggressive behaviour and anger in different situations. In addition to dispositional measures of aggressiveness and anger predicting aggressive behaviour and anger in each of the anger‐provoking situations, other personality variables were also related to aspects of the road rage response (e.g. conscientiousness, agreeableness, narcissism, and extraversion). Attributions and personality traits accounted for unique variance in the outcomes, and there were only sporadic effects of attributions partially mediating the relationships between personality variables and responses to the anger‐provoking situations. Therefore, it is unlikely that the relationships between personality traits and responses to anger‐provoking situations are completely mediated by attributional processing.
Air-stable phosphine oxides as preligands for catalytic activation reactions of C-Cl, C-F, and C-H bonds
Authors: Ackermann Lutz , Born Robert , Spatz Julia H. , Althammer Andreas , Gschrei Christian J.
Published: March 2006

Studies on the use of easily accessible heteroatom-substituted secondary phosphine oxides as preligands for cross-coupling reactions are described. These air-stable sterically hindered phosphine oxides allow for efficient palladium-catalyzed Suzuki- and nickel-catalyzed Kumada-coupling reactions using electronically deactivated aryl chlorides. In addition, they enable nickel-catalyzed coupling reactions of magnesium organyls with aryl fluorides at ambient temperature, and ruthenium-catalyzed coupling reactions of aryl chlorides via C-H bond activation. Finally, the application of modular diamino phosphine chlorides as preligands for a variety of transition-metal-catalyzed C-C and C-N bond formation reactions employing electron-rich aryl chlorides is presented.
Palladium-mediated cascade or multicomponent reactions: A new route to carbo- and heterocyclic compounds
Authors: Balme Geneviève , Bouyssi Didier , Monteiro Nuno
Published: March 2006

In recent years, new processes based on transition-metal-mediated intramolecular addition reaction of heteronucleophiles and stabilized carbon nucleophiles to unactivated alkenes and alkynes have been developed in our laboratory. In this article, we summarize a number of recent synthetic applications of these new processes. Emphasis is placed on the development of multicomponent reactions based on a Pd-mediated intramolecular cyclization coupled with a carbon-carbon bond-forming reaction. Applications of this methodology to the synthesis of natural lignans are also reported.