bluuebunny/crossref_metadata_2025 huggingface dataset:
Laparoscopic nephrectomy for a single‐system ectopic ureter draining a small, dysplastic and poorly functioning kidney in children
Authors: Jeong Byong Chang , Lim Dae Jung , Lee Sang Chul , Choi Hwang , Kim Hyeon Hoe
Published: January 2007

Purposes:  To assess the efficacy of laparoscopic nephrectomy for a single‐system ectopic ureter draining a dysplastic kidney in children.

Patients and Methods:  Between February 1999 and September 2005, 16 girls with a mean age of 6.2 years (range: 2–15 years) presented with urinary incontinence accompanied by regular voiding since birth (15 patients) and vaginitis (one patient). Ultrasonography, intravenous urography and a 99mTc‐DMSA renal scan showed the presence of only a single kidney in all cases. Computed tomography (CT) showed a dysplastic kidney definitely in nine patients, structures suspicious of dysplastic kidney in three cases, and no dysplastic kidney in four cases. Magnetic resonance imaging was carried out in the four cases with non‐visualized dysplastic kidneys by CT, and showed a suspicious lesion in only one case, and no lesion in the other three patients. All patients underwent transperitoneal laparoscopic nephrectomy for a dysplastic kidney.

Results:  Laparoscopy identifies all dysplastic kidneys easily, even in those cases in which dystrophic kidney could not be identified by preoperative imaging. Dysplastic kidneys and ectopic ureters were removed successfully in all 16 patients. Mean operative time was 109 min (range: 40–155 min) with little intraoperative bleeding. Mean postoperative hospital stay was 2.6 days (range: 2–4 days). No intraoperative complication was encountered, except in one single case, in which a small bowel injury occurred during open Hasson’s procedure. All patients became dry soon after the operation.

Conclusion:  Laparoscopic nephrectomy for an ectopic ureter draining into a dysplastic kidney is a safe and effective method, and can be carried out successfully, despite a failure by preoperative imaging studies to localize the dysplastic kidney.
Impact of unilateral interposition sural nerve graft on the recovery of sexual function after radical prostatectomy in Japanese men: A preliminary study
Authors: Saito Seiichi , Namiki Shunichi , Numahata Kenji , Satoh Makoto , Ishidoya Shigeto , Ito Akihiro , Nakagawa Haruo , Kaiho Yasuhiro , Sanada Takehiko , Yamada Atsushi , Arai Yoichi
Published: January 2007

Purpose:  To determine the effect of an interposition nerve graft on sexual function after radical prostatectomy.

Methods:  This study includes 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation. Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle. Twenty‐one and 31 patients underwent bilateral nerve‐sparing (BNS) and unilateral nerve‐sparing (UNS) surgery without a nerve graft, respectively. As the age of patients was significantly younger in the UNG group than in the other groups, age‐matched analysis also was conducted. Sexual function, evaluated by a self‐administered questionnaire using the University of California Los Angeles‐Prostate Cancer Index, was compared statistically among the three groups.

Results:  In the age‐matched analysis, the postoperative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months postoperatively. The difference in the SXF score between the UNG and UNS groups began to appear after 6 months postoperatively and increased steadily with time. However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of comorbidities were different between the UNG and UNS groups.

Conclusions:  The difference of the SXF score between the UNG and UNS groups increased with time after 6 months postoperatively. However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.
A pilot study of the assessment of the quality of life, functional results, and complications in patients with an ileal neobladder for invasive bladder cancer
Authors: Harano Masahiko , Eto Masatoshi , Nakamura Motonobu , Hasegawa Yoshihiro , Kano Motonori , Yamaguchi Akito , Naito Seiji
Published: January 2007

Objective:  To assess the functional results, health‐related quality of life (QOL) outcomes, and complications in patients with an ileal neobladder in comparison to those with cutaneous diversion (ileal conduit and cutaneostomy).

Methods:  Between September 1992 and February 2003, we consecutively performed an ileal neobladder (the Studer method) in 30 patients and cutaneous diversion in 38 patients. In August 2004, questionnaires were mailed to 54 patients. The questionnaire included the validated health‐related quality of life (QOL) questionnaire, SF‐36 General Health Survey, and a urinary incontinence questionnaire. We also evaluated the functional results in patients with an ileal neobladder and the postoperative complications in patients with both urinary diversions.

Results:  The data from 41 patients (21 ileal neobladder procedures and 20 cutaneous diversions) were available for the analysis. No differences in the overall QOL were observed between the two groups. Complete daytime and night‐time urinary continence was achieved in the 21 patients (100%) and 13 patients (61.9%), respectively. The mean value of the maximum flow rate was 15 ± 12 mL/min in the 21 neobladder patients. There were 19 early complications in 18 patients (60.0%) and seven late complications in six patients (20.0%) with an ileal neobladder. However, there were 15 early complications in 14 patients (36.8%) and eight late complications in six patients (15.8%) with cutaneous diversions.

Conclusion:  The findings regarding the health‐related QOL and the frequency of complications in the neobladder group and those in the cutaneous diversion group were similar. However, the functional results and the status of urinary continence in the neobladder patients were satisfactory.
Anorectal cancer following topical formalin application for haemorrhagic radiation proctitis
Authors: Stern D. R. , Steinhagen R. M.
Published: January 2007

Objective  Topical formalin has been used as an effective treatment for haemorrhagic radiation proctitis. In the course of reviewing our experience with this modality, we identified two patients who developed anorectal cancer during the follow‐up period.

Method  From 2001 to 2005, 49 patients who received pelvic radiation for treatment of prostate, rectal or endometrial cancer subsequently developed haemorrhagic radiation proctitis. Four percent formalin was applied in the office setting under direct visualization with a rigid proctoscope and without sedation. Response to treatment was then reviewed.

Results  Seventy‐eight per cent of patients reported a complete response to formalin application. Only 14% were refractory to formalin treatment. Two patients subsequently presented with anorectal cancer.

Conclusion  Topical formalin application in the outpatient setting appears to be an effective first‐line treatment for haemorrhagic radiation proctitis. We report the first cases of anorectal cancer which developed subsequent to formalin application. Pelvic irradiation is known to increase the risk of developing a second malignancy, therefore it is impossible to determine what, if any, role formalin application played in the development of the second malignancies.
Do low‐molecular‐weight heparins influence the healing process in colon anastomosis?
Authors: Krzesniak‐Wszola N. , Bielecki K. , Ostrowski J.
Published: January 2007

Anastomosis leakage is one of the most serious complications of colorectal surgery. A role for extracellular matrix remodelling in the healing process of the colon wall has been recently postulated. Changes in matrix metalloproteinase (MMP) activity in the intestinal wall occurring prior to elective resection and primary anastomosis appear to be responsible for dehiscence leading to anastomosis. Thrombophylaxis using low‐molecular‐weight heparins is routinely administered to all patients during the perioperative period. However, adverse antiproliferative and proapoptotic effects such as limitation of bioavailability of growth factors and angiogenesis inhibition have been characterized in various cell types as a result of heparin administration. It is also likely that relationships exist between extracellular matrix homeostasis and the coagulation/fibrinolysis system. We hypothesize that subcutaneous administration of LMWHs (low‐molecular‐weight heparins) may influence matrix metalloproteinase activity in the colon wall and increase the risk of postoperative leakage.
Increased apoptosis and decreased proliferation of colorectal cancer cells using insulin‐like growth factor binding protein‐4 gene delivered locally by gene transfer
Authors: Durai R. , Yang S. Y. , Sales K. M. , Seifalian A. M. , Goldspink G. , Winslet M. C.
Published: January 2007

Objective  Insulin‐like growth factor (IGF)‐I induces proliferation of transformed cells. Its binding proteins (IGFBP) are involved in local regulation of IGF. This study assessed the effects of overexpression of IGFBP‐4 on the development of cancer in vivo.

Method  Nude mice were subcutaneously inoculated with HT‐29 colorectal cancer cells (3 × 106). When the tumour became visible (1 week after inoculation), animals received either 150 μg of mammalian expression vector containing IGFBP‐4 cDNA or vector alone (n = 6 each) by peritumoural injection. Tumour size was measured during the growth. After 3 weeks of IGFBP‐4 induction, animals were killed and tumour tissue samples were collected for examining the level of IGFBP‐4 expression. Tumour mitotic activities were determined by counting numbers of mitotic cells on the tissue section. Apoptosis was investigated by terminal deoxynucleotidyl transferase‐mediated dUDP nick end labelling assay.

Results  Following IGFBP‐4 treatment, tumour showed large necrotic areas, significantly increased numbers of apoptotic cells (36.67 ± 7.36 vs 7.07 ± 1.91, P < 0.01 vs control), decreased cells undergoing mitosis (2.31 ± 0.32 vs 3.61 ± 0.27, P < 0.01 vs control) and higher expression of IGFBP‐4 (P < 0.05 vs control).

Conclusion  IGFBP‐4 gene transfer increased apoptosis and decreased mitosis, but tumour volume was not significantly altered possibly due to cellular debris filling the centre of tumours.
Early symptomatic recurrence after intestinal resection in Crohn's disease is unpredictable
Authors: Kurer M. A. , Stamou K. M. , Wilson T. R. , Bradford I. M. J. , Leveson S. H.
Published: January 2007

Objective  To identify predictors of early symptomatic recurrence of Crohn's disease (CD) after surgical resection.

Method  We studied a cohort of 128 patients who had undergone at least one intestinal resection for CD. Factors that might predict early recurrence were documented for analysis using a standardized pro forma. These comprised age, gender, family history, extra‐intestinal manifestations, smoking, complicated disease at first presentation, site of disease, preoperative inflammatory markers, involvement of resection margins, orientation and method of anastomosis and postoperative medical therapy. All symptomatic recurrences were confirmed by endoscopic, radiological, or operative means. We defined early recurrence as that which occurred within 36 months of first surgery. Univariate analysis was conducted to compare the distribution of each factor in those who developed early recurrence (n = 48) and those who remained disease free for the first 36 months (n = 50).

Results  Of the 128 patients studied, 98 fulfilled the inclusion criteria of at least 36 months of follow up. Of these patients, 48 (49%) patients developed recurrence. Trends towards fewer early recurrences were seen in patients with colonic disease (33%vs 56%, P = 0.068). Of the current smokers, 60% developed early recurrence compared with 43% of nonsmokers (P = 0.269). All other factors examined were similarly distributed between the two groups. Metronidazole as adjuvant treatment does not appear to protect against early symptomatic recurrence.

Conclusion  This study shows that early symptomatic postoperative recurrence of CD remains unpredictable. Against expectation, abstinence from smoking and postoperative adjuvant metronidazole did not appear to protect against early symptomatic recurrence.
An observational cohort study investigating the cardiovascular safety of tadalafil when prescribed in primary care in England: mortality due to ischaemic heart disease
Authors: Hazell Lorna , Boshier Andrew , Harris Scott , Wilton Lynda V. , Shakir Saad A.W.
Published: January 2007

OBJECTIVE

To examine the cardiovascular safety of tadalafil, a phosphodiesterase type‐5 inhibitor used for treating erectile dysfunction in patients prescribed this drug by general practitioners (GPs) in England in 2003, focusing on mortality due to ischaemic heart disease (IHD).

PATIENTS AND METHODS

Patients in this observational cohort study were identified from dispensed prescriptions for tadalafil issued by GPs from February to November 2003. Demographic and outcome data were requested from patients’ GPs using a postal questionnaire. A standardized mortality ratio (SMR) was calculated using indirect standardization for all deaths from IHD or myocardial infarction (MI) in male patients who were prescribed tadalafil, regardless of whether they were taking tadalafil at the time, compared to those in the English male population (2002).

RESULTS

Clinical information was obtained for 6266 patients; patient sex could not be confirmed for 37 but in the remaining 6229 the median age was 61 years (interquartile range 53–68). The age was not specified for 2361 (37.7%) of the patients. Excluding patients not taking tadalafil at the time of the event, cardiovascular events included chest pain in 20, angina in 18, MI in 15 (including six fatal) and IHD in 11 (including five fatal). There were also six deaths where the cause was not ascertained; five of these patients were known to be male. Comparison of mortality due to IHD or MI for men with those in the English male population (2002) provided an SMR of 0.91 (95% confidence interval 0.50–1.48).

CONCLUSIONS

The results from this study suggest a similar incidence of death due to IHD or MI in men prescribed tadalafil to that in the male English population. However, due to possible under‐reporting and the limitations of using an external comparator, these results should be interpreted in context with other studies on the cardiovascular effects and safety of tadalafil.
A prospective, randomized, double‐blind trial to evaluate the role of a short reducing course of oral corticosteroid therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome
Authors: Bates Sylvia M. , Hill Valerie A. , Anderson John B. , Chapple Christopher R. , Spence Rosemary , Ryan Claire , Talbot Martin D.
Published: January 2007

OBJECTIVES

To assess the validity of our observational experience that a short course of oral prednisolone therapy might be of value in the management of symptoms of chronic pelvic pain syndrome (CPPS) in men.

PATIENTS AND METHODS

Twenty‐one men with CPPS (inflammatory or non‐inflammatory) for ≥6 months, and who had failed to improve with standard antibiotic therapy, were randomized to receive either a 1‐month reducing course of oral prednisolone (nine) or an equivalent placebo regimen (12 men). The outcome measures used were the McGill Pain Questionnaire, the Hospital Anxiety and Depression Scale (HADS), General Health Questionnaire‐30 (GHQ‐30) and the National Institute of Health Chronic Prostatitis Symptom Index (NIH‐CPSI), which were completed at baseline and 3 months.

RESULTS

Outcomes were analysed for the 18 patients (six treated, 12 placebo) who completed the 3 months of follow‐up. At both baseline and 3 months, respectively, there was no statistically significant difference between the groups in the NIH‐CPSI total score (P = 0.48 and 0.62; Mann–WhitneyU‐test), or in the HADS (anxiety,P = 0.85 and 0.67; depressionP = 0.96 and 0.74), and there was no significant improvement or deterioration over time. Although not statistically significant, there was a trend to improvement in the depression score for the active group (P = 0.13). However, the clinical significance is doubtful, as both baseline and follow‐up depression scores were within the normal range. No patient had clinically negative changes in depression. A 3‐month follow‐up analysis was not possible for the McGill Pain Questionnaire or GHQ‐30 as not all patients completed the questionnaire.

CONCLUSIONS

Whilst the study showed no clinical benefit of using corticosteroids in the management of CPPS, the few patients recruited limited the validity of firm conclusions from the data. There was a trend towards an improvement of depression levels amongst subjects. The study highlights the difficulties of recruitment and illustrates the complex psychological profiles of patients with CPPS.
Perceptions of female body weight and shape among indigenous and urban Europeans
Authors: SWAMI VIREN , TOVÉE MARTIN J.
Published: January 2007

Two important cues to female physical attractiveness are body mass index (BMI) and body shape as measured by the waist‐to‐hip ratio (WHR). This study examined the relative contribution of both cues in three culturally distinct populations. A total of 119 Finnish, Sámi and British male observers rated a set of un‐edited photographs of women with known BMI and WHR. The results showed that there were significant differences in preferences for physical attractiveness, with the indigenous Sámi preferring figures with larger BMIs and more tolerant of heavyweight figures than either Finnish participants in Helsinki or Britons in London, who were indistinguishable in their preferences for slim figures. The findings are discussed in terms of evolutionary psychological explanations of mate selection, and sociocultural theories which emphasizes the learning of preferences for body sizes in social and cultural contexts.
Semantic interference on a phonological task in illiterate subjects
Authors: REIS ALEXANDRA , FAÍSCA LUÍS , MENDONÇA SUSANA , INGVAR MARTIN , PETERSSON KARL MAGNUS
Published: January 2007

Previous research suggests that learning an alphabetic written language influences aspects of the auditory‐verbal language system. In this study, we examined whether literacy influences the notion of words as phonological units independent of lexical semantics in literate and illiterate subjects. Subjects had to decide which item in a word‐ or pseudoword pair was phonologically longest. By manipulating the relationship between referent size and phonological length in three word conditions (congruent, neutral, and incongruent) we could examine to what extent subjects focused on form rather than meaning of the stimulus material. Moreover, the pseudoword condition allowed us to examine global phonological awareness independent of lexical semantics. The results showed that literate performed significantly better than illiterate subjects in the neutral and incongruent word conditions as well as in the pseudoword condition. The illiterate group performed least well in the incongruent condition and significantly better in the pseudoword condition compared to the neutral and incongruent word conditions and suggest that performance on phonological word length comparisons is dependent on literacy. In addition, the results show that the illiterate participants are able to perceive and process phonological length, albeit less well than the literate subjects, when no semantic interference is present. In conclusion, the present results confirm and extend the finding that illiterate subjects are biased towards semantic‐conceptual‐pragmatic types of cognitive processing.
Deliberate self‐harm in 15‐year‐old adolescents: A pilot study with a modified version of the Deliberate Self‐Harm Inventory
Authors: LUNDH LARS‐GUNNAR , KARIM JESSICA , QUILISCH EVA
Published: January 2007

The purpose of the present study was to investigate the rate of deliberate self‐harm in 15‐year‐old Swedish adolescents, gender differences in this behavior, and possible associations with self‐esteem and mindfulness. For this purpose, we developed a simplified version of Gratz's (2001) Deliberate Self‐Harm Inventory (DSHI), and carried out a pilot study with 123 adolescents from three different schools in southern Sweden. The results showed that 65.9% of the adolescents reported having engaged in some kind of deliberate self‐harm at least once; 41.5% reported at least one kind of self‐harm more than once; and 13.8% reported at least one kind of deliberate self‐harm behavior “many times”. Although there were no overall gender differences in self‐harm, the girls reported significantly more of cutting wrists, arms and other body areas than the boys. High rates of deliberate self‐harm were associated with low self‐esteem and low mindfulness.
Export Market Participation, Investments in R&D and Worker Training, and the Evolution of Firm Productivity
Authors: Aw Bee Yan , Roberts Mark J. , Winston Tor
Published: January 2007

This paper uses micro panel data for firms in the Taiwanese electronics industry in 1986, 1991 and 1996 to investigate a firm's decision to invest in two sources of knowledge – participation in the export market and investments in R&D and/or worker training – and assess their effect on the firm's future productivity. The firm's decisions to export and invest in R&D and/or worker training are modelled with a bivariate probit model that recognises the interdependence of the decisions. The effect of these investments on the firm's future productivity trajectory is then modelled while controlling for the selection bias introduced by endo‐genous firm exit. The findings indicate a significant interaction effect between exporting and R&D investments and future productivity, after controlling for size, age and current productivity. Firms that undertake both investment activities have significantly higher future productivity than firms that do one or neither. In addition, these firms are more likely to continue investing in these activities leading to further productivity gains. These findings are consistent with the hypothesis that export experience is an important source of productivity growth for Taiwanese firms and that firm investments in R&D and worker training facilitate their ability to benefit from their exposure to the export market.
Outward FDI and Productivity: Micro‐evidence from Slovenia
Authors: Damijan Jože P. , Polanec Sašo , Prašnikar Janez
Published: January 2007

This paper uses a rich data set of Slovenian manufacturing firms active in the period 1994–2002 that contains information on outward FDI and exports to different markets in order to test three empirical hypotheses that relate the decision for outward FDI to total factor productivity. First, the evidence supports the hypothesis proposed by Helpman, Melitz and Yeaple (2004) that more productive firms are more likely to invest in a foreign affiliate. Second, the hypothesis proposed by Head and Ries (2003) that less productive firms may be encouraged to invest in low‐income countries is rejected by the data. However, the main contribution of the paper is to confirm the third hypothesis that required firm's productivity increases with the number of markets that the firm serves, i.e. there is a positive relationship between the number of a firm's foreign affiliates and its total factor productivity.
A Spatial Model for the Needle Losses of Pine-Trees in the Forests of Baden-Württemberg: An Application of Bayesian Structured Additive Regression
Authors: Augustin Nicole H. , Lang Stefan , Musio Monica , Von Wilpert Klaus
Published: January 2007

The data that are analysed are from a monitoring survey which was carried out in 1994 in the forests of Baden-Württemberg, a federal state in the south-western region of Germany. The survey is part of a large monitoring scheme that has been carried out since the 1980s at different spatial and temporal resolutions to observe the increase in forest damage. One indicator for tree vitality is tree defoliation, which is mainly caused by intrinsic factors, age and stand conditions, but also by biotic (e.g. insects) and abiotic stresses (e.g. industrial emissions). In the survey, needle loss of pine-trees and many potential covariates are recorded at about 580 grid points of a 4 km × 4 km grid. The aim is to identify a set of predictors for needle loss and to investigate the relationships between the needle loss and the predictors. The response variable needle loss is recorded as a percentage in 5% steps estimated by eye using binoculars and categorized into healthy trees (10% or less), intermediate trees (10–25%) and damaged trees (25% or more). We use a Bayesian cumulative threshold model with non-linear functions of continuous variables and a random effect for spatial heterogeneity. For both the non-linear functions and the spatial random effect we use Bayesian versions of P-splines as priors. Our method is novel in that it deals with several non-standard data requirements: the ordinal response variable (the categorized version of needle loss), non-linear effects of covariates, spatial heterogeneity and prediction with missing covariates. The model is a special case of models with a geoadditive or more generally structured additive predictor. Inference can be based on Markov chain Monte Carlo techniques or mixed model technology.
A Generalization of the Beta–Binomial Distribution
Authors: Rodríguez-Avi J. , Conde-Sánchez A. , Sáez-Castillo A. J. , Olmo-Jiménez M. J.
Published: January 2007

The paper describes a distribution generated by the Gaussian hypergeometric function that may be seen as a generalization of the beta–binomial distribution. It is expressed as a generalized beta mixture of a binomial distribution. This new mixing distribution allows the existence of a mode and an antimode, which is very useful for fitting some data sets. Two examples illustrate the greater versatility of the new distribution compared with the beta–binomial distribution.
GOES-8 X-Ray Sensor Variance Stabilization Using the Multiscale Data-Driven Haar–Fisz Transform
Authors: Fryzlewicz Piotr , Delouille Véronique , Nason Guy P.
Published: January 2007

We consider the stochastic mechanisms behind the data that were collected by the solar X-ray sensor (XRS) on board the GOES-8 satellite. We discover and justify a non-trivial mean–variance relationship within the XRS data. Transforming such data so that their variance is stable and its distribution is taken closer to the Gaussian distribution is the aim of many techniques (e.g. Anscombe and Box–Cox). Recently, new techniques based on the Haar–Fisz transform have been introduced that use a multiscale method to transform and stabilize data with a known mean–variance relationship. In many practical cases, such as the XRS data, the variance of the data can be assumed to increase with the mean, but other characteristics of the distribution are unknown. We introduce a method, the data-driven Haar–Fisz transform, which uses the Haar–Fisz transform but also estimates the mean–variance relationship. For known noise distributions, the data-driven Haar–Fisz transform is shown to be competitive with the fixed Haar–Fisz methods. We show how our data-driven Haar–Fisz transform method denoises the XRS series where other existing methods fail.
ROBERT JENSON ON THE PRE‐EXISTENCE OF CHRIST
Authors: CRISP OLIVER D.
Published: January 2007

In his recent two‐volume Systematic Theology, Robert Jenson offers an account of Christ's pre‐existence that is, in several important respects, an original contribution to the literature. In this article, I offer a critical interaction with Jenson's doctrine. In particular, I show that what Jenson has to say about (a) divine eternity and (b) the relationship between philosophy and theology, have important bearings on his construal of Christ's pre‐existence and, in the final analysis, skew what he has to say on the matter. I conclude that Jenson's account of this doctrine, though suggestive and insightful in several respects, is unsuccessful, indeed, incoherent, as it stands.
THEOLOGY FROM A FRACTURED VISTA: SUSAN NEIMAN'S EVIL IN MODERN THOUGHT
Authors: ROSSI PHILIP J.
Published: January 2007

Evil in Modern Thought, Susan Neiman's account of the intellectual trajectory of modernity, employs the trope “homeless” to articulate deep difficulties that affirmations of divine transcendence and of human capacities to acknowledge transcendence face in a contemporary context thoroughly marked by fragmentation, fragility, and contingency. The “hospitality” of the Incarnation, which makes a fractured world a place for divine welcoming of the human in all its contingency and brokenness, is proposed as locus for theological engagement with Neiman's appropriation of a Kantian sense of hope as the readiness to resist evil in a world seemingly bereft of welcome.
Experience with the use of a first‐line regimen of stavudine, lamivudine and nevirapine in patients in the TREAT Asia HIV Observational Database
Authors: Zhou J , Paton NI , Ditangco R , Chen Y‐MA , Kamarulzaman A , Kumarasamy N , Lee CKC , Li PCK , Merati TP , Phanuphak P , Pujari S , Vibhagool A , Zhang F , Chuah J , Frost KR , Cooper DA , Law MG ,   on behalf of the TREAT Asia HIV Observational Database
Published: January 2007

Background

The antiretroviral treatment (ART) combination of stavudine, lamivudine and nevirapine (d4T/3TC/NVP) is the most frequently used initial regimen in many Asian countries. There are few data on the outcome of this treatment in clinic cohorts in this region.

Methods

We selected patients from the TREAT Asia HIV Observational Database (TAHOD) who started their first ART regimen with d4T/3TC/NVP. Treatment change was defined as cessation of therapy or the addition or change of one or more drugs. Clinical failure was defined as diagnosis with an AIDS‐defining illness, or death while on d4T/3TC/NVP treatment.

Results

The rate of treatment change among TAHOD patients starting d4T/3TC/NVP as their first antiretroviral treatment was 22.3 per 100 person‐years, with lower baseline haemoglobin (i.e. anaemia) associated with slower rate of treatment change. The rate of clinical failure while on d4T/3TC/NVP treatment was 7.3 per 100 person‐years, with baseline CD4 cell count significantly associated with clinical failure. After d4T/3TC/NVP was stopped, nearly 40% of patients did not restart any treatment and, of those who changed to other treatment, the majority changed to zidovudine (ZDV)/3TC/NVP and less than 3% of patients changed to a protease inhibitor (PI)‐containing regimen. The rates of disease progression on the second‐line regimen were similar to those on the first‐line regimen.

Conclusion

These real‐life data provide an insight into clinical practice in Asia and the Pacific region. d4T/3TC/NVP is maintained longer than other first‐line regimens and change is mainly as a result of adverse effects rather than clinical failure. There is a need to develop affordable second‐line antiretroviral treatment options for patients with HIV infection in developing countries.
Predictive factors for immunological and virological endpoints in Thai patients receiving combination antiretroviral treatment
Authors: Srasuebkul P , Ungsedhapand C , Ruxrungtham K , Boyd MA , Phanuphak P , Cooper DA , Law MG ,   the HIV‐NAT study team
Published: January 2007

Background

Routine CD4 count and HIV viral load monitoring is a financial barrier in developing countries.

Methods

We assessed factors associated with CD4 counts ≤200 cells/μL and detectable viral load in Thai HIV‐infected patients receiving antiretroviral therapy (ART) at the HIV Netherlands Australia Thailand Research Collaboration and the Thai Red Cross AIDS Research Centre (HIV‐NAT). Univariate and multivariate Cox proportional hazards models for multiple treatment failures were used to determine factors related to CD4 counts ≤200 cells/μL and detectable viral load. Multivariate Cox proportional hazards models for CD4 counts ≤200 cells/μL were developed with and without viral load in order to build models applicable to contexts in which viral load is not available.

Results

Four hundred and seventeen patients were included in the study. Fifty‐four per cent were male, and the median CD4 count and log10 viral load at baseline were 283 cells/μL and 4.3 log10 HIV‐1 RNA copies/mL, respectively. Independent factors related to CD4 count ≤200 cells/μL were CD4 count at baseline [hazards ratio (HR) 0.20/100 cells/μL; 95% confidence interval (CI) 0.17–0.23] and changes in CD4 count (HR 0.22/100 cells/μL; 95% CI 0.17–0.28). Factors in multivariate models (in which viral load was considered for inclusion) were CD4 count at baseline (HR 0.21/100 cells/μL; 95% CI 0.18–0.24), changes in CD4 count (HR 0.25/100 cells/μL; 95% CI 0.19–0.32) and detectable viral load (HR 1.94; 95% CI 1.20–3.13). Predictive factors (independent of viral load) were triple ART or highly active antiretroviral therapy (HAART) (HR 0.28; 95% CI 0.22–0.36) and detectable viral load at baseline (HR 2.96; 95% CI 2.24–3.91).

Conclusions

CD4 count at baseline and changes in CD4 count were important in predicting CD4 counts ≤200 cells/μL. Triple ART and detectable viral load at baseline were important in predicting detectable viral load.
Mitochondrial DNA assessment in adipocytes and peripheral blood mononuclear cells of HIV‐infected patients with lipodystrophy according to a validated case definition
Authors: Casula M , Van Der Valk M , Wit FW , Nievaard MA , Reiss P
Published: January 2007

Background

Several studies have compared mitochondrial DNA (mtDNA) content in tissue from HIV‐1‐infected patients on highly active antiretroviral therapy with and without evidence of lipodystrophy, the diagnosis of which was based on subjective clinical assessment.

Objectives

The aim of this study was to assess the utility of mtDNA quantification as a marker of HIV‐associated lipodystrophy as diagnosed using a published validated case definition.

Methods

We assessed mtDNA content in adipocytes from both thigh and lumbar subcutaneous adipose tissue (n=19), and in peripheral blood mononuclear cells (PBMC) (n=26), obtained from 26 HIV‐1‐infected patients classified as having lipodystrophy (n=17) or not having lipodystrophy (n=9) according to the validated definition derived from the Lipodystrophy Case Definition Study.

Results

The adipocyte and PBMC mtDNA contents did not significantly differ between patients with and without lipodystrophy. Lipodystrophy patients had been treated for significantly longer times, especially with dideoxynucleoside analogues. In both groups, the thigh adipocyte mtDNA content was significantly greater than that of the lumbar region. When all patients were considered together, a statistically significant negative correlation was found between thigh adipocyte mtDNA content and stavudine treatment duration.

Conclusions

Longer exposure to dideoxynucleoside analogues was associated with lipodystrophy, and longer exposure to stavudine was correlated with lower mtDNA content in thigh adipocytes. However, a single measurement of adipocyte mtDNA content in this limited sample of patients could not distinguish between patients with and without clinical lipodystrophy. The observed variation in mtDNA content between different subcutaneous adipose tissue depots argues for harmonization of future studies regarding which depot to biopsy.
Circles of Support and Accountability: Engaging Community Volunteers in the Management of High‐Risk Sexual Offenders
Authors: WILSON ROBIN J. , McWHINNIE ANDREW , PICHECA JANICE E. , PRINZO MICHELLE , CORTONI FRANCA
Published: January 2007

Abstract: The release to the community of a sexual offender is frequently accompanied by intense coverage in the news media. Too often, the type of coverage these releases receive serves only to force many offenders into hiding or out of one community and into another. Forced to move to another community, the scapegoating process starts all over again. It is well known that secrecy and isolation are critical elements in sexual offending behaviour. Thus, forcing offenders into hiding does nothing to increase community safety or offender accountability and, arguably, increases the risk that new victims will be created. The most problematic releases are those in which sexual offenders arrive in a community with few or no links, and with little access to appropriate treatment and supervisory services. This article outlines a restorative approach to the risk management of high‐risk sexual offenders in Canada using professionally‐facilitated volunteerism. The Circles of Support and Accountability model grew out of an ad hoc, faith‐based response to a situation much like that described above in South‐Central Ontario, Canada. The resultant pilot project has since reached its twelfth anniversary and the model has proliferated both nationally and internationally.
The Sexual Health and Behaviour of Male Prisoners: The Need for Research
Authors: STEWART ELAINE C.
Published: January 2007

Abstract: Sexually transmitted infections (STIs) are a major public health problem in the United Kingdom (UK) and the limited data available may suggest high prevalence rates (especially of HIV, hepatitis B and C) in the escalating male prison population. Sex, rape and injecting drug use are a part of prison life, yet screening for STIs does not routinely take place and there are inconsistencies in the availability of condoms and other harm‐reduction devices. Numerous characteristics of male prisoners (for example, social disadvantage, drug dependency, younger age, black ethnic origin, on remand), their offences (drug, sex, violent) and overcrowded prisons (for example, sharing cells, staff shortages, enforced idleness, transfers) are also considered ‘high risk’ from a sexual health perspective, especially the spread of STIs between prisoners and into the wider population when they are released. There is, therefore, an urgent need for research so that sexual health information and HIV/STI prevention initiatives can be successfully targeted.
Current Responses to Sexual Grooming: Implication for Prevention
Authors: CRAVEN SAMANTHA , BROWN SARAH , GILCHRIST ELIZABETH
Published: January 2007

Abstract: This article aims to outline current responses to sexual grooming; specific attention will be given to new legislation introduced in England and Wales under the Sexual Offences Act 2003. Following an outline of this new legislation, consideration will be given to its effectiveness, including practical difficulties that are likely to restrict its scope. Issues to be discussed include: poor definition and understanding of sexual grooming, scope of legislation in relation to non‐Internet grooming, difficulties in identifying sexual grooming, and a failure of the new legislation to be truly preventative. The article concludes by supporting Richard Laws's suggestion that the most effective prevention of child sexual abuse would result from adopting a public health approach.
Serum‐ and glucocorticoid‐inducible kinase1 enhances contextual fear memory formation through down‐regulation of the expression of Hes5
Authors: Lee Ching T. , Ma Yun L. , Lee Eminy H. Y.
Published: January 2007

Mitogen‐activated protein kinase/extracellular signal‐regulated kinase plays an important role in memory formation and directly phosphorylates serum‐ and glucocorticoid‐inducible kinase1 (SGK1) at Ser78. In this study, we examined the role and mechanism of SGK1 Ser78 activation involved in contextual fear memory formation in rats. Results revealed that SGK1 Ser78 phosphorylation was increased 30 min, 1 h and 3 h after training. Transient transfection of the dominant negative mutant of sgk, sgkS78A, to hippocampal neurons impaired, whereas transfection of the constitutively active sgk, sgkS78D, enhanced fear retention. Microarray analysis identified 14 genes that showed more than threefold alteration in their gene expression in sgkS78A‐transfected animals 6 h after training. One of them is Hairy and Enhancer of split 5 (Hes5). The expression level of Hes5 is approximately 4.4‐fold higher in sgkS78A‐transfected animals. Further analyses revealed that Hes5 level is markedly decreased after training in control animals, but sgkS78A markedly increased Hes5 level after training. RNA interference experiment showed that shHes5 dose‐dependently enhanced fear retention, whereas over‐expression of Hes5 impaired fear retention. Moreover, shHes5 at a lower concentration completely blocked the memory‐impairing effect of sgkS78A. These results together suggest that Hes5 negatively regulates contextual fear memory formation and SGK activation down‐regulates Hes5 expression to enhance fear retention.
Nerve growth factor‐stimulated neuronal differentiation induces changes in P2 receptor expression and nucleotide‐stimulated catecholamine release
Authors: Arthur David B. , Taupenot Laurent , Insel Paul A.
Published: January 2007

Extracellular nucleotides modulate synaptic transmission and neuronal communication by activating purinergic 2 (P2) (nucleotide) receptors. Here, we assessed changes in the regulation by nucleotides and their receptors of an important physiological response – release and uptake of catecholamines – that accompanies sympathoadrenal neuronal differentiation. Nerve growth factor (NGF)‐promoted differentiation of pheochromocytoma 12 (PC12) cells enhanced the ability of the non‐hydrolyzable ATP analog, ATPγS, to stimulate catecholamine (norepinephrine, NE) release and this enhancement occurred without a significant alteration in NE uptake. In addition to ATPγS, 2‐MeSATP and αβMeATP, P2X receptor‐selective agonists, caused greater NE release from NGF‐differentiated than from undifferentiated PC12 cells. NGF‐differentiated PC12 cells had altered mRNA expression of several P2Y and P2X receptors but protein expression was only increased for P2X, in particular P2X1‐4,receptors and P2X, but not P2Y, receptor inhibitors blunted the NGF‐promoted enhancement in nucleotide‐regulated catecholamine release. Surprisingly, siRNA directed against P2X2, the receptor with the highest expression, failed to alter NE release by ATPγS. These findings indicate that sympathetic neuronal differentiation by NGF increases both the expression of P2X receptor sub‐types and their regulation of catecholamine release. NGF‐promoted increased expression of P2X receptors thus appears to be a physiologically important response that characterizes sympathetic neuronal differentiation.
Kainate receptors and RNA editing in cholinergic neurons
Authors: Olsen Douglas P. , Dunlap Kathleen , Jacob Michele H.
Published: January 2007

Parasympathetic ganglia are considered simple relay systems that have cholinergic input and output, with modulation occurring centrally. Greater complexity is suggested, however, by our showing here that avian ciliary ganglion (CG) neurons also express a different excitatory receptor type –ionotropic glutamate receptors of the kainate subtype (KARs). This is the first report of glutamate receptor expression in the CG and KAR expression in any cholinergic neuron. We show that KARs form functional channels on CG neurons. KARs localize to CG neuron axons and somata as well as axons and terminals of pre‐synaptic inputs to the CG. Glutamate transporters are expressed on Schwann cells that surround synapses on neuronal somata, and may provide a local source of glutamate. CG neurons express multiple KAR subunit mRNAs (GluR5, GluR7, and KA1), and their relative levels change dramatically during axon outgrowth and synaptic differentiation. The developmental role for KARs may depend upon their calcium permeability, a property regulated by mRNA editing. We show GluR5 editing increases predominantly at the time CG axons contact peripheral targets. Our data suggest that glutamatergic signaling may function as a local circuit mechanism to modulate excitability and calcium signaling during synapse formation and maturation in the CG in vivo.
Clinical pharmacology and therapeutic use of antioxidant vitamins
Authors: Rodrigo Ramón , Guichard Cristián , Charles Roberto
Published: January 2007

The clinical use of antioxidants has gained considerable interest during the last decade. It was suggested from epidemiological studies that diets high in fruits and vegetables might help decrease the risk of cardiovascular disease. Therefore, supplements of vitamins C and E were applied through protocols aimed to prevent diseases such as atherosclerosis, preeclampsia or hypertension, thought to be mediated by oxidative stress. Despite the biological properties of these vitamins could account for an effective protection, as shown by several clinical and experimental studies, their efficacy remains controversial in the light of some recent clinical trials and meta‐analyses. However, the methodology of these studies, criteria for selection of patients, the uncertain extent of progression of the disease when initiating supplementation, the lack of mechanistic studies containing basic scientific aspects, such as the bioavailability, pharmacokinetic properties, and the nature of the antioxidant sources of vitamins, could account for the inconsistency of the various clinical trials and meta‐analyses assessing the efficacy of these vitamins to prevent human diseases. This review presents a survey of the clinical use of antioxidant vitamins E and C, proposing study models based on the biological effects of these compounds likely to counteract the pathophysiological mechanisms able to explain the structural and functional organ damage.
Circadian and time‐dependent variability in tacrolimus pharmacokinetics
Authors: Park Sung‐In , Felipe Claudia R. , Pinheiro‐Machado Paula G. , Garcia Riberto , Tedesco‐Silva Helio , Medina‐Pestana Jose O.
Published: January 2007

Tacrolimus (TAC) is considered a critical dose drug. The purpose of our study was to investigate circadian and time‐dependent changes in TAC pharmacokinetics over the first year after kidney transplantation. Pharmacokinetic (PK) studies were performed in 26 recipients of first living donor kidney transplants at day 7 after morning (a.m.) and evening (p.m.) doses of TAC. Additional serial PK studies were carried out in nine patients at month 6 (M6) and month 12 (M12). Blood samples were collected before 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 h after TAC administration. Demographics, TAC and adjunctive immunosuppressive doses, hematology, and biochemistry were recorded in each PK study. Mean age was 37 years, body mass index 23 kg/m2, 58% males, and 85% Caucasian. Higher AUC (231.4 vs. 220 ng·h/mL, P = 0.06) and Cmax (34.1 ± 12.6 vs. 24.4 ± 9.8 ng/mL, P < 0.001), and lower Tmax (1.6 ± 0.8 vs. 2.7 ± 2.0 h, P = 0.05) values were observed comparing a.m. and p.m. administrations. Comparing D7, M6 and M12, there was a significant increase in dose‐normalized AUC (31.4 ± 22.2 vs. 50.1 ± 33 vs. 39.2 ± 24.4 ng·h/mL/mg, P = 0.005), Cmax (4.4 ± 2.4 vs. 7.8 ± 3.5 vs. 6.0 ± 3.3 ng/mL/mg, P < 0.001) and Tmax (1.6 ± 1.1 vs. 1.7 ± 0.4 vs. 1.8 ± 0.8 h, P = 0.006), respectively. Over the first year the intraindividual variability of dose‐normalized AUC, Cmax and C0 were 82%, 72%, and 90%, respectively. No significant changes were observed comparing inter‐individual variability of dose‐normalized AUC (21%, 24%, 33%), Cmax (46%, 45%, 55%), C0 (49%, 83%, 81%) at D7, M6 and M12, respectively. We observed a good correlation between a.m. and p.m. TAC AUC (r2 = 0.90) and C0 (r2 = 0.88). Tacrolimus pharmacokinetics display circadian variation suggesting a slower and delayed absorption phase at nighttime. Tacrolimus also showed time‐dependent PK changes, suggesting an improvement in absorption during the first 6 months. Despite circadian variation we observed good correlations between a.m. and p.m. TAC AUC (r2 = 0.90) and C0 (r2 = 0.88) and between C0 and total daily TAC exposure (a.m. + p.m. AUC) suggesting that trough‐guided therapeutic monitoring is still a reliable and simple strategy to optimize the clinical use of TAC.