bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitomycin C and Etoposide in Advanced Colorectal Carcinoma
Authors: Seminara P. , Pastore C. , Iascone C. , Cicconetti F. , Nigita G. , Ielapi T. , Franchi F.
Published: March 2007

Background: Aim of this study was to evaluate the activity of a combination regimen of chemotherapy containing mitomycin C (MMC) and etoposide (ETO) in advanced colorectal carcinoma. Methods: Fourteen pretreated patients received MMC 2 mg/m2 and ETO 60 mg/m2, days 1–5 every 28 days. The clinical study was interrupted since no clinical response was observed in 14 patients following four courses of chemotherapy. An in vitro study was then performed on HTC-8 cell line. The cytotoxic activity of the MMC/ETO combination was tested by sulforhodamine B assay and the type of drug interaction was assessed using the method of Chou and Talalay. Cell cycle perturbations and apoptosis were evaluated by flow cytometry. Results: While MMC and ETO were singularly active, the simultaneous exposure of cells to both drugs and the sequence MMC→ETO ensued in antagonistic interaction at all levels of killed cell fraction. Conversely, the sequence ETO→MMC produced a synergistic interaction. Conclusions: These results suggest that the activity of the MMC/ETO combination is highly schedule-dependent and that the experimental drug associations should be based on a preclinical rationale before clinical trials are designed.
Production of Inflammatory Molecules in Peripheral Blood Mononuclear Cells from Severely Glucose-6-Phosphate Dehydrogenase-Deficient Subjects
Authors: Sanna Francesca , Bonatesta Rosa Rita , Frongia Bruno , Uda Sabrina , Banni Sebastiano , Melis Maria Paola , Collu Maria , Madeddu Clelia , Serpe Roberto , Puddu Silvana , Porcu Giovanna , Dessì Sandra , Batetta Barbara
Published: March 2007

Objective: We have previously demonstrated that Mediterranean glucose-6-phosphate dehydrogenase (G6PD)-deficient peripheral blood mononuclear cells (PBMC) respond to mitogenic stimuli with a reduced cholesterol synthesis and growth. In the present study, we have investigated the release of inflammatory molecules by PBMC following a mitogenic stimulus, as well as the transformation to foam cells of monocyte-derived macrophages from severely G6PD-deficient and normal subjects. Methods and Results: PBMC from G6PD-deficient subjects produced interleukin (IL)-1β and IL-6 to a lower extent compared with normal subjects. 5-Hydroxyeicosatetraenoic acid, a primary product of 5-lipoxygenase, was slightly decreased. Tumour necrosis factor-α and IL-1β secretion was significantly reduced in monocyte-derived macrophages. No difference was found in IL-10 secretion, whereas transforming growth factor-β was invariably found to be significantly higher in G6PD-deficient cells. In cells incubated with acetylated low-density lipoprotein, cholesterol esterification and its storage in lipid droplets were lower than in normal G6PD cells. Conclusions: We conclude that by reducing the secretion of inflammatory molecules by PBMC and increasing the secretion of transforming growth factor-β and the capability of monocyte-derived macrophages to accumulate lipid droplets and convert into foam cells, G6PD deficiency may confer a partial protection against atherosclerosis leading to the reduced risk of cardiovascular diseases reported in G6PD-deficient subjects.
Central Mesenteric Lymph Node BER-Ep4+ Cells in Colorectal Cancer: Challenge to Sentinel Node Concept?
Authors: Schurr Paulus G. , Behnke Sophia , Kaifi Jussuf T. , Bogoevski Dean , Link Bjoern , Mann Oliver , Strate Tim , Pantel Klaus , Izbicki Jakob R. , Yekebas Emre
Published: March 2007

Background: The role of sentinel lymph nodes in colorectal cancer remains unclear. Methods: Cryosections from central para-aortic mesenterial lymph nodes were stained using mAb BER-Ep4. Overall survival and distant recurrence were calculated using Kaplan-Meier plots. Results: All patients (n = 48) were free of distant metastases and curatively resected (R0). 23 pN0, 13 pN1 and 12 pN2 stages were found. 21/48 patients (44%) showed BER-Ep4+ cells in their central lymph nodes (7/23 pN0, 8/13 pN1, 6/12 pN2). In 6/23 pN0 patients, BER-Ep4+ cells were also found in locoregional nodes (p = 0.03, Fisher’s exact test). pN status predicted overall survival (p = 0.006, Kaplan-Meier curve, log-rank test). An impact was exerted by central mesenteric BER-Ep4+ cells on overall survival (p = 0.009 in pN0 patients, p = 0.07 for all pN) and distant recurrence-free survival (p = 0.001 in pN0 patients, p = 0.007 for all pN). Multivariate analysis showed an independent prognostic effect on overall survival in pN0 patients (p = 0.022). Conclusion: Central lymph nodes are sentinels of disease not amenable to extended lymphadenectomy and might identify patients at risk of distant organ recurrence.
Randomized Controlled Trial to Assess the Role of Raised Anal Pressures in the Pathogenesis of Symptomatic Early Hemorrhoids
Authors: Chauhan Ashutosh , Thomas Shaji , Bishnoi Prem Kumar , Hadke Niladhar S.
Published: March 2007

Background: Increased maximum resting anal pressures (MRAP) have been found in patients with large prolapsed hemorrhoids undergoing hemorrhoidectomy, but their pathogenic role is controversial especially in view of the sphincteric damage that occurs with open and stapled procedures. This prospective randomized clinical trial was conducted to compare anal pressure changes in early symptomatic hemorrhoidal disease before and after successful treatment with band ligation or injection sclerotherapy, and to compare these pressures with those in normal asymptomatic controls. Methods: 32 patients with symptomatic grade II hemorrhoids were randomized to treatment with either band ligation or injection sclerotherapy. Anal manometry was done before treatment and 8 weeks after completion of treatment, and compared with 20 normal age-matched controls. Results: The pretreatment values in both study groups were similar to each other (69.38 cm H2O, 95% CI 58.67–80.08, vs. 67.75 cm H2O, 95% CI 56.86–78.64; p = 0.790), but were significantly higher (p = 0.0001 in both groups) than in the controls (45.25 cm H2O, 95% CI 38.36–52.14). After successful completion of treatment, there was a highly significant drop in the MRAP in both study groups (p = 0.0001 in group A, and p = 0.001 in group B) reaching normal values. Conclusions: Our study shows that even in early-stage hemorrhoids, the anal pressures are significantly raised, but after successful treatment with band ligation or injection sclerotherapy, these pressures return to normal, showing that they do not play a pathogenic role but are secondary to the congested hemorrhoidal cushions.
Quality of Life in Disease-Free Gastric Adenocarcinoma Survivors: Impacts of Clinical Stages and Reconstructive Surgical Procedures
Authors: Huang Chi-Cheng , Lien Heng-Hui , Wang Pa-Chun , Yang Jiao-Chiao , Cheng Chan-Yeh , Huang Ching-Shui
Published: March 2007

Aim: To investigate health-related quality of life data of disease-free gastric adenocarcinoma survivors, with special emphasis on the roles of clinical stages and reconstructive surgical procedures. Methods: We performed a cross-sectional study in 51 disease-free gastric adenocarcinoma patients. The patients had been followed for at least 6 (median 17, range from 6 months to 2 years) months after initial radical surgery. The Taiwan Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cancer 30 (EORTC QLQ-C30) and the supplementary gastric cancer module QLQ-STO22 were used as outcome measures. Results: Patients with earlier-/advanced-stage diseases (American Joint Committee on Cancer stages I and II vs. III and IV) had a similar quality of life in terms of global health status and functional and symptomatic well-being. Subtotal gastrectomy outweighed total gastrectomy with better role function and less nausea/vomiting and appetite loss. Multivariate regression analyses also proved that proximal gastric preservation was predictive of better role function, less nausea/vomiting, and less appetite loss. Conclusions: Gastric adenocarcinoma survivors may enjoy a similar life quality, regardless of their original disease stages. Functional preservation may have marginal advantages to improve patients’ quality of life by reducing symptomatic nausea, vomiting, and appetite loss postoperatively.
Autonomic Nerve Stimulation Reverses Ventricular Repolarization Sequence in Rabbit Hearts
Authors: Mantravadi Rajkumar , Gabris Bethann , Liu Tong , Choi Bum-Rak , de Groat William C. , Ng G. André , Salama Guy
Published: March 2007

Sympathetic activity and spatial dispersion of repolarization (DOR) have been implicated as mechanisms that promote arrhythmia vulnerability; yet there are no direct measurements of the effects of autonomic nerve stimulation on DOR. Rabbit hearts were perfused in a Langendorff apparatus with full sympathetic and parasympathetic innervation and were optically mapped to measure action potential durations and DOR (apex–base) over the left ventricles. DOR was measured under sinus rhythm, during bilateral sympathetic nerve stimulation (SNS) and right and/or left vagus nerve stimulation and was compared with DOR during isoproterenol (100 nmol/L) or acetylcholine (1 μmol/L) infusion. In sinus rhythm, repolarization started at the apex and systematically progressed toward the base. SNS (10 to 15 Hz) increased DOR by 29% (from Δaction potential duration=17±0.7 to −22±1.6 ms, n=6) and reversed DOR as the direction of repolarization from apex→base in sinus rhythm shifted to base→apex in 5 to 15 seconds after SNS. DOR flipped back to its sinus rhythm DOR pattern 115±15 seconds after the interruption of SNS. During right or left vagus nerve stimulation, there was no change in the direction of DOR, but bilateral vagus nerve stimulation increased and reversed DOR to base→apex direction. Infusion of isoproterenol or acetylcholine increased DOR but did not alter the direction of repolarization sequences. These findings demonstrate that bilateral autonomic activity (SNS or vagus nerve stimulation) cause reversible shifts of apex–base DOR and that the spatial heterogeneities of autonomic effects on the ventricles are most likely attributable to a greater innervation at the base than the apex of the heart.
Calcium-Independent Negative Inotropy by β-Myosin Heavy Chain Gene Transfer in Cardiac Myocytes
Authors: Herron Todd J. , Vandenboom Rene , Fomicheva Ekaterina , Mundada Lakshmi , Edwards Terri , Metzger Joseph M.
Published: March 2007

Increased relative expression of the slow molecular motor of the heart (β-myosin heavy chain [MyHC]) is well known to occur in many rodent models of cardiovascular disease and in human heart failure. The direct effect of increased relative β-MyHC expression on intact cardiac myocyte contractility, however, is unclear. To determine the direct effects of increased relative β-MyHC expression on cardiac contractility, we used acute genetic engineering with a recombinant adenoviral vector (AdMYH7) to genetically titrate β-MyHC protein expression in isolated rodent ventricular cardiac myocytes that predominantly expressed α-MyHC (fast molecular motor). AdMYH7-directed β-MyHC protein expression and sarcomeric incorporation was observed as soon as 1 day after gene transfer. Effects of β-MyHC expression on myocyte contractility were determined in electrically paced single myocytes (0.2 Hz, 37°C) by measuring sarcomere shortening and intracellular calcium cycling. Gene transfer-based replacement of α-MyHC with β-MyHC attenuated contractility in a dose-dependent manner, whereas calcium transients were unaffected. For example, when β-MyHC expression accounted for ≈18% of the total sarcomeric myosin, the amplitude of sarcomere-length shortening (nanometers, nm) was depressed by 42% (151.0±10.7 [control] versus 87.0±5.4 nm [AdMYH7 transduced]); and genetic titration of β-MyHC, leading to 38% β-MyHC content, attenuated shortening by 57% (138.9±13.0 versus 59.7±7.1 nm). Maximal isometric cross-bridge cycling rate was also slower in AdMYH7-transduced myocytes. Results indicate that small increases of β-MyHC expression (18%) have Ca
2+
transient-independent physiologically relevant effects to decrease intact cardiac myocyte function. We conclude that β-MyHC is a negative inotrope among the cardiac myofilament proteins.
Synchrotron Radiation Coronary Microangiography for Morphometric and Physiological Evaluation of Myocardial Neovascularization Induced by Endothelial Progenitor Cell Transplantation
Authors: Iwasaki Hiroto , Fukushima Kazuhito , Kawamoto Atsuhiko , Umetani Keiji , Oyamada Akira , Hayashi Saeko , Matsumoto Tomoyuki , Ishikawa Masakazu , Shibata Toshihiko , Nishimura Hiromi , Hirai Hidekazu , Mifune Yutaka , Horii Miki , Sugimura Kazuro , Suehiro Shigefumi , Asahara Takayuki
Published: March 2007

Background—

Therapeutic effect of stem cell transplantation (SCTx) for myocardial neovascularization has been evaluated by histological capillary density in small animals. However, it has been technically difficult to obtain imaging evidence of collateral formation by conventional angiography.

Methods and Results—

Peripheral blood CD34+ and CD34− cells were isolated from patients with critical limb ischemia. PBS, CD34− cells, or CD34+ cells were intramyocardially transplanted after ligating LAD of nude rats. Coronary angiography of ex vivo beating hearts 5 and 28 days after the treatment was performed using the third generation synchrotron radiation microangiography (SRM), which has potential to visualize vessels as small as 20 μm in diameter. The SRM was performed pre and post sodium nitroprusside (SNP) to examine vascular physiology at each time point. Diameter of most collateral vessels was 20 to 120 μm, apparently invisible size in conventional angiography. Rentrop scores at day 28 pre and post SNP were significantly greater in CD34+ cell group than other groups (
P
<0.01). To quantify the extent of collateral formation, angiographic microvessel density (AMVD) in the occluded LAD area was analyzed. AMVD on day 28 post SNP, not pre SNP, was significantly augmented in CD34+ cell group than other groups (
P
<0.05). AMVD post SNP closely correlated with histological capillary density (
R
=0.82,
P
<0.0001).

Conclusions—

The SRM, capable of visualizing microvessels, may be useful for morphometric and physiological evaluation of coronary collateral formation by SCTx. The novel imaging system may be an essential tool in future preclinical/translational research of stem cell biology.
Increased Expression of Glutathione Reductase in Macrophages Decreases Atherosclerotic Lesion Formation in Low-Density Lipoprotein Receptor–Deficient Mice
Authors: Qiao Mu , Kisgati Marta , Cholewa Jill M. , Zhu Weifei , Smart Eric J. , Sulistio Melanie S. , Asmis Reto
Published: March 2007

Objective—

Thiol oxidative stress leads to macrophage dysfunction and cell injury, and has been implicated in the development of atherosclerotic lesions. We investigated if strengthening the glutathione-dependent antioxidant system in macrophages by overexpressing glutathione reductase (GR) decreases the severity of atherosclerosis.

Methods and Results—

Bone marrow cells infected with retroviral vectors expressing either enhanced green fluorescent protein (EGFP) or an EGFP-fusion protein of cytosolic GR (GR
cyto
-EGFP) or mitochondrial GR (GR
mito
-EGFP) were transplanted into low-density lipoprotein receptor-deficient mice. Five weeks after bone marrow transplantation, animals were challenged with a Western diet for 10 weeks. No differences in either plasma cholesterol and triglyceride levels or peritoneal macrophage content were observed. However, mice reconstituted with either GR
cyto
-EGFP or GR
mito
-EGFP–expressing bone marrow had lesion areas (
P
<0.009) that were 32% smaller than recipients of EGFP-expressing bone marrow. In cultured macrophages, adenovirus-mediated overexpression of GR
cyto
-EGFP or GR
mito
-EGFP protected cells from mitochondrial hyperpolarization induced by oxidized low-density lipoprotein.

Conclusion—

This study provides direct evidence that the glutathione-dependent antioxidant system in macrophages plays a critical role in atherogenesis, and suggests that thiol oxidative stress-induced mitochondrial dysfunction contributes to macrophage injury in atherosclerotic lesions.
Adaptation to Social Adversity Is Associated With Stroke Incidence
Authors: Surtees Paul G. , Wainwright Nicholas W.J. , Luben Robert L. , Wareham Nicholas J. , Bingham Sheila A. , Khaw Kay-Tee
Published: March 2007

Background and Purpose—

Laboratory-based studies have suggested that individual differences in cardiovascular reactivity and stress adaptive capacity are associated with stroke incidence. We test the hypothesis that sense of coherence (SOC), a marker of social stress adaptive capacity, is associated with incident stroke in a population-based prospective cohort study.

Methods—

A total of 20 629 participants, aged 41 to 80 years, in the UK European Prospective Investigation into Cancer (EPIC)-Norfolk study, who had not previously experienced a stroke, completed assessments that included SOC and details of their experience of life events during adulthood. An index of adaptation was constructed from responses to questions concerning over 80 000 adverse life events.

Results—

During 145 000 person-years of follow-up (mean 7.1 years), 452 participants experienced either a fatal or nonfatal stroke event. A strong (as opposed to a weak) SOC was associated with a reduced rate of stroke incidence (rate ratio 0.76; 95% CI, 0.60 to 0.96) after adjustment for age, sex, pre-existing myocardial infarction, diabetes, hypertension treatment, family history of stroke, cigarette smoking, systolic blood pressure, obesity, social class, education, hostility and depression. No sex difference in this association was observed. Measures of social adversity occurrence and impact were not associated with stroke incidence, whereas faster reported adaptation to adverse event exposure was associated with a reduced rate of stroke incidence (rate ratio 0.89; 95% CI, 0.81 to 0.98; per standard deviation change in adaptation score, adjusted for age and sex).

Conclusions—

Stress adaptive capacity is a potentially important candidate risk factor for stroke.
Different Degrees of Hypothermia After Experimental Stroke
Authors: Kollmar Rainer , Blank Tobias , Han Junliang L. , Georgiadis Dimitrios , Schwab Stefan
Published: March 2007

Background and Purpose—

The neuroprotective role of mild therapeutic hypothermia was established in animal models of cerebral ischemia. Still, several issues, including optimal target temperature, remain unclear. The optimal depth of hypothermia in a rat model of focal cerebral ischemia was investigated.

Methods—

Eighty-four male Wistar rats (n=84) were subjected to filament occlusion of the middle cerebral artery for 90 minutes. Sixty animals were equally split into 6 groups kept at core temperatures of 37°C, 36°C, 35°C, 34°C, 33°C, and 32°C over a period of 4 hours starting 90 minutes after middle cerebral artery occlusion. Twenty-four hours later, after performing a neuroscore, animals were killed and brains examined for infarct size, edema, and invasion of leukocytes. In the second part, 24 animals (8 per group) were kept at 33°C, 34°C, and 37°C for 4 hours, allowed to survive for 5 days, and underwent additional investigation of transferase dUTP nick-end labeling.

Results—

In the first part, one animal in each treatment group and 2 animals in group 37°C died. The infarct size and edema were smaller for 34°C and 33°C compared with all other groups (
P
<0.05) over 24 hours. These animals also had better functional outcome (
P
<0.05) with an advantage for 34°C versus 33°C (
P
<0.05). Leukocyte count was lower for 34°C and 33°C as compared with the 37°C group. Similar results were obtained in the second part of the study with an advantage for 34°C versus 33°C.

Conclusion—

Our results suggest that the optimal depth of therapeutic hypothermia in temporary middle cerebral artery occlusion is 34°C.
Restoration Declensions, Divine Consolations: The Work of John Foxe in 1664 Massachusetts
Authors: Myles Anne G.
Published: March 2007

The article identifies the author of an anonymous 1664 New England tract, Divine Consolations for Mourners of Sion. Selecting passages from Englishman John Foxe's Book of Martyrs (1563), the tract speaks through that text to address a generational crisis in Massachusetts Bay as well as the recent troubling incursion of Quakers.
The Attractiveness of Enriched and Impoverished Options
Authors: Yinlong Zhang  , Mittal Vikas
Published: March 2007

The authors propose that there is a systematic impact of a person's activated self-construal (interdependent vs. independent) on the evaluation of enriched and impoverished options. This hypothesis is tested using a cross-country comparison of participants from China and the United States (Study 1) and by priming self-construal (Study 2) and regulatory focus (Study 3). Results show that people with an independent self-construal and a promotion focus perceive enriched options as more attractive than impoverished options. Conversely, people with an interdependent self-construal and a prevention focus perceive enriched options as less attractive than impoverished options. Mediation analyses show that the effect of cultural orientation operates through self-construal. In turn, self-construal operates through activated regulatory focus. Analysis of cognitive responses shows that the effect of regulatory focus is mediated by positive/negative thoughts about option attributes.
Implicit Theories About Groups and Stereotyping
Authors: Rydell Robert J. , Hugenberg Kurt , Ray Devin , Mackie Diane M.
Published: March 2007

The consequences of holding an entity (i.e., the belief that a group's characteristics are fixed) or incremental (i.e., the belief that a group's characteristics are malleable) implicit theory about groups was examined for stereotyping and perceptions of group entitativity. Two studies showed that implicit theories about groups affect stereotyping by changing perceptions of group entitativity. Study 1 found that entity theorists were more likely to stereotype than incremental theorists and that perception of group entitativity significantly accounted for this relation. In Study 2, implicit theories of groups were manipulated via instruction set and entity theorists stereotyped more and perceived groups as more entitative than incremental theorists. Again, the effect of implicit theory was significantly, although partially, mediated by perceptions of group entitativity. The roles of implicit theories about groups and perceptions of group entitativity are discussed regarding stereotyping.
Perceptions of Parents, Mental Health, and School Among Canadian Adolescents from the Provinces and the Northern Territories
Authors: Volk Anthony A. , Craig Wendy , Boyce William , King Matthew
Published: March 2007

The authors examined whether perceptions of parents and personal mental health significantly influenced perceptions of school achievement and enjoyment in a large sample of Canadian adolescents. Responses from more than 10,000 Canadian adolescents in the Health Behaviour in School-Aged Children (HBSC) survey were used to create a Parental Support Index, a Mental Health Index, and a School Index. They found a significant, medium-sized effect between the parent index and the school index. They found a similar but smaller effect for mental health. The findings were consistent for adolescents across the 10 southern provinces. However, among adolescents from the two northern territories the Parental Support Index was not significant whereas demographic factors and mental health played a larger role in predicting scores on the School Index.
Equipping School Psychologists to Address Another Risky Behavior
Authors: Dickson Laurie , Derevensky Jeffrey L.
Published: March 2007

School psychologists are assuming an increasingly important role in ensuring youth have the mental and emotional health to succeed academically. Although considerable attention has been paid to a number of adolescent high-risk behaviors including drug and alcohol use, cigarette smoking, and sexually transmitted diseases, little attention has been paid to youth gambling behaviors. Youth problem gambling has been largely overlooked as a mental and public health issue although it can result in serious mental heath consequences and impede students’ academic success. The current state of knowledge regarding adolescent gambling is presented. Prevention and intervention initiatives that are accessible to school psychologists are outlined, and the challenges to school psychologists in implementing youth problem gambling prevention programs are discussed.
Temperament Styles of Zimbabwe and U.S. Children
Authors: Oakland Thomas , Mpofu Elias , Sulkowski Michael
Published: March 2007

Temperament styles of 600 Zimbabwe children are described and compared to those of 3,200 U.S. children. Gender and age differences are described for children in Zimbabwe and compared to U.S. children. Results indicate that Zimbabwe children generally prefer extroverted to introverted styles, practical to imaginative styles, feeling to thinking styles, and organized to flexible styles. Gender differences were found on one style: in contrast to males, females are more likely to prefer extroverted styles. Age differences are seen on extroversion-introversion, thinking-feeling, and organized-flexible styles. In contrast to U.S. children, those in Zimbabwe tend to express higher preferences for practical, feeling, and organized styles. Implications for practice are discussed.
Possible Relationships Between Depressive Symptoms and Reading
Authors: Stringer Ronald W. , Heath Nancy
Published: March 2007

One hundred and fifty-five students (average age of 127 months) were tested using the WRAT-3 reading and arithmetic subtests, the Self-Perception Profile for Children with Learning Disabilities (SPPLD) and the Children’s Depression Inventory (CDI). One year later they were again tested with the same instruments. The authors hypothesised that increases in depressive symptoms would lead to lowered performance in reading and arithmetic, over and above any changes in performance due to self-perceived competence in those areas. Although academic self-concept scores did not account for any significant variation in academic growth/decline, CDI scores did account for a small but significant portion of variance in academic score changes. Depressive symptoms, even at nonpatho-logic levels, are able to affect academic performance over time.
Sexual Coercion Among Adolescents
Authors: Lacasse Anne , Mendelson Morton J.
Published: March 2007

Adolescence is a transitional period when the pressure to engage in romantic and sexual relationships can leave teenagers feeling confused and at risk for sexual coercion. Our studies investigated characteristics of male and female perpetrators and victims of peer sexual coercion, focusing on self-esteem, sexist attitudes, and involvement in nonsexual deviant behaviors, such as drugs and alcohol. The participants, all of whom were in Grades 8 to 11, were from Quebec, Canada. They completed self-report measures. Female victims had lower self-esteem and more sexist attitudes than other female participants, whereas male perpetrators had more sexist attitudes than other male participants. Furthermore, all victims and perpetrators were more likely to be involved in other types of nonsexual deviance.
Prevalence of restless legs syndrome and REM sleep behavior disorder in multiple sclerosis
Authors: Gómez-Choco M.J. , Iranzo A. , Blanco Y. , Graus F. , Santamaria J. , Saiz A.
Published: March 2007

A total of 135 consecutive, unrelated, multiple sclerosis (MS) patients were interviewed for symptoms suggestive of restless legs syndrome (RLS) and REM sleep behavior disorder (RBD), using semi-structured questionnaires. Some 118 unrelated healthy controls of similar sex and age distribution were included for comparison. Patients and controls with equivocal symptoms were re-evaluated by a sleep disorders specialist and video-polisomnography in those who fulfilled the criteria for RBD. We did not find significant differences in frequency (13.3 versus 9.3%), proportion of females (66.7 versus 58.5%), and mean age (42.1±12.6 versus 43±7.8 years) among MS patients and controls with RLS. RBD was found in three patients (1.4%), one associated with antidepressant intake, but in none of the controls. Our study shows that RLS in MS is not more frequent than in the general population, and that RBD, although uncommon, may occur in the setting of this neurological disease. Multiple Sclerosis 2007; 13: 805-808. http://msj.sagepub.com
Communicating the diagnosis of multiple sclerosis - a qualitative study
Authors: Solari A. , Acquarone N. , Pucci E. , Martinelli V. , Marrosu M.G. , Trojano M. , Borreani C. , Messmer Uccelli M.
Published: March 2007

Studies on communicating the diagnosis of multiple sclerosis (MS) are few, and all reveal communication and information deficits. We explored the personal experience of diagnosis communication of people with MS and health professionals, using a qualitative methodology. Data were obtained from two sets of focus group meetings (FGM) with people with MS (total 23; 16 females; age range: 23-70) and one FGMs with health professionals (four neurologists, three psychologists, two nurses). The methods of framework analysis were applied to meeting transcripts to identify key topics and categories. The experience of communicating/receiving an MS diagnosis was highly varied; all patients reported the moment as powerfully evocative and unforgettable. Very poor levels of support and information were sometimes given. Although diagnosis communication had improved in more recent experience, all felt it should be further improved with appropriate setting (privacy, no interruptions, sufficient time), information tailored to the individual, and continuity of care. Such improvements imply a more meaningful patientneurologist relationship, and also structural and organisational changes. Multiple Sclerosis 2007; 13: 763-769. http://msj.sagepub.com
Validation of the NARCOMS registry: diagnosis
Authors: Marrie R.A. , Cutter G. , Tyry T. , Campagnolo D. , Vollmer T.
Published: March 2007

The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is a patient registry, wherein the diagnoses of multiple sclerosis (MS) are unverified. We compared self-reported diagnoses of registry participants to physician-reported diagnoses, and with diagnoses based on medical records review. Registry participants with more than one of the following: age of onset <10 or >50 years, no bladder symptoms or fatigue, or zero or more than four relapses in the last year, were considered atypical. All others were considered typical. We sent letters to participants describing the study, surveyed treating physicians regarding the participants' diagnosis, and reviewed medical records. Diagnosis was classified by the McDonald and Poser criteria. Of the 240 participants sampled, 109 were in active registry status with accurate contact information. Of these, 52 consented, 29 refused and 28 did not respond (weighted response rate 76.3±4.5%). Some 37 of 38 physician surveys confirmed the diagnosis of MS (98.8±1.2%). After reviewing 41 medical records, we classified 53.2±8.9% of participants as definite MS, 16.9±6.8% as possible MS, while the remainder had insufficient data for diagnostic confirmation. We confirmed a diagnosis of MS in 98.7±1.3% of participants based on records review, physician survey or telephone interview, supporting the validity of the diagnoses reported by NARCOMS participants. Multiple Sclerosis 2007; 13: 770-775. http://msj.sagepub.com
The differential diagnosis of Axis I psychopathology presenting to a university-based multiple sclerosis clinic
Authors: Brousseau KM , Arciniegas DB , Carmosino MJ , Corboy JR
Published: March 2007

Patients carrying a presumptive diagnosis of multiple sclerosis (MS) sometimes present with non-specific clinical signs and symptoms that may be, at least in part, somatic manifestations of psychiatric conditions. This retrospective study was undertaken to identify psychiatric diagnoses among 63 patients whose initial clinical evaluations suggested a primary psychiatric, rather than a primary neurological, etiology for their symptoms. Some 92% of patients met Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) criteria for one or more primary psychiatric disorders, most often including somatoform, mood, and anxiety disorders. Accurate identification and diagnosis of psychiatric conditions producing pseudoneurological or non-specific somatic symptoms is necessary for both treatment and medico-economic reasons. Multiple Sclerosis 2007; 13: 749-753. http://msj.sagepub.com
Cell surface adhesion molecules and cytokine profiles in primary progressive multiple sclerosis
Authors: Ukkonen Maritta , Wu Xingchen , Reipert Birgit , Dastidar Prasun , Elovaara Irina
Published: March 2007

Objective We evaluated the utility of adhesion molecule (AM) and cytokine/chemokine expressions in blood and cerebrospinal fluid (CSF) as markers of disease activity in primary progressive multiple sclerosis (PPMS).

Methods The expressions of AMs and the levels of 17 cytokines in patients with PPMS (n = 25) were compared with those in secondary progressive MS (SPMS) (n = 18) and controls (n =11) and correlated with the volumes of focal and atrophic changes on MRI.

Results The expressions of very late activation antigen 4 (VLA-4), lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) in blood and CSF were higher in PPMS than in controls. Comparison between PPMS and SPMS showed higher levels of ICAM-1 in blood and CSF in PPMS, while the level of the vascular adhesion molecule (VCAM-1) was higher only in blood. There was no difference in the levels of cytokines in serum or CSF between PPMS and SPMS or controls, but evidence suggesting intrathecal synthesis of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) was found in PPMS. The expressions of CSF VLA-4 in PPMS correlated with the total volume of cerebral lesions and the number of diffuse brain lesions in MRI, while the amount of LFA-1 in CSF correlated with the number of spinal T2 lesions. The level of serum MIP-1β correlated with the T2 lesion load and EDSS score in PPMS.

Conclusions The upregulated expressions of AMs in blood and CSF and evidence for intrathecal synthesis of MCP-1 and IL-8 in PPMS indicate the importance of inflammatory changes in the pathogenesis of PPMS. Multiple Sclerosis 2007; 13: 701-707. http://msj.sagepub.com
Magnetization transfer ratio measurement in multiple sclerosis normal-appearing brain tissue: limited differences with controls but relationships with clinical and MR measures of disease
Authors: Vrenken H. , Pouwels P.J.W. , Ropele S. , Knol D.L. , Geurts J.J.G. , Polman C.H. , Barkhof F. , Castelijns J.A.
Published: March 2007

We investigated the magnetization transfer ratio (MTR) of normal-appearing white (NAWM) and grey matter (NAGM) in a relatively large group of multiple sclerosis (MS) patients, and the relations of MTR changes with clinical disability. MTR was measured in 66 MS patients (12 PP, 35 RR, 19 SP) and 23 healthy controls, using a whole-brain 3D-FLASH technique corrected post-hoc for B1-induced variation. Histogram parameters of conservatively selected NAWM and cortical NAGM were analysed using Bonferroni-corrected ANOVA with age as covariate. Additionally, manually outlined regions of interest were analysed using a multilevel method. Lesions had low MTR (mean 22.7±6.9%), but NAWM exhibited limited changes: MTR histogram peak position was 32.8±1.0% in controls and 32.4±0.9% in MS patients, with a significant decrease compared to controls only in SPMS patients (31.9±1.1%, p=0.045). Cortical NAGM histograms did not differ significantly between patients and controls. In SPMS, regional mean MTR was significantly decreased in corpus callosum and hippocampus. MTR histogram parameters of NAGM and NAWM were correlated with EDSS and MSFC scores, with lesion volume and with normalized brain volume. We conclude that disease-induced MTR changes were small in MS NAWM and NAGM, but did correlate with clinical decline, lesion volume and overall cerebral atrophy. Multiple Sclerosis 2007; 13: 708-716. http://msj.sagepub.com
A dose comparison study of IVIG in postpartum relapsing-remitting multiple sclerosis
Authors: Haas Judith , Hommes Otto Roelf
Published: March 2007

Untreated patients with relapsing-remitting multiple sclerosis (RRMS) have an elevated risk of exacerbation in the first 3 months postpartum. Pregnant patients (n =173) with RRMS and with at least one relapse in the two years before pregnancy were enrolled in this multinational, multicentre, randomized double-blind clinical trial investigating different doses of intravenous immunoglobulin (IVIG) treatment in the 6 months postpartum. Group I (unloaded) received 150 mg/kg body weight (BW) IVIG on Day 1, then placebo infusions on Day 2 and Day 3. Group II (loaded) received 450, 300 and 150 mg/kg BW on Days 1, 2 and 3 respectively. Both groups then received 150 mg/kg BW five times in four-weekly intervals. The ratio of patients remaining relapse-free during the first 3 months postpartum did not differ significantly between both groups (81.5% in Group II versus 75.6% in Group I). The ratio of relapse-free patients was independent of dosage in the subgroup of patients breastfeeding for at least 3 months (89% in Group I versus 90% in Group II). The mean annualized relapse rate (ARR) after pregnancy did not show an increased risk for exacerbation, but returned to prepregnancy level within 3 months independent of dosage. The treatment was well tolerated. Multiple Sclerosis 2007; 13: 900-908. http://msj.sagepub.com
Diffusion-weighted imaging predicts cognitive impairment in multiple sclerosis
Authors: Benedict Ralph H.B. , Bruce Jared , Dwyer Michael G. , Weinstock-Guttman Bianca , Tjoa Chris , Tavazzi Eleonora , Munschauer Frederick E. , Zivadinov Robert
Published: March 2007

Following a previous study with diffusion tensor imaging, we investigated the correlation between diffusion-weighted imaging (DWI) and cognitive dysfunction in multiple sclerosis (MS). We studied 60 MS patients (mean age 45.8±9.0 years) using 1.5-T MRI. Disease course was RR=40 and SP = 20. Mean disease duration was 12.8±8.7 years. Mean EDSS was 3.4±1.7. Whole brain, gray and white matter normalized volumes were calculated on 3D SPGR T1-WI using a fully automated Hybrid SIENAX method. Parenchymal mean diffusivity (PMD) maps were created after automated segmentation of the brain parenchyma and cerebrospinal fluid using T2-WI and DW images. Histogram analysis was performed and DWI indices of peak position (PP), peak height (PH), mean parenchymal diffusivity (MPD) and entropy were obtained. Neuropsychological (NP) evaluation emphasized auditory/verbal and visual/spatial memory, as well as processing speed and executive function. We found significant correlations between DWI and performance in all cognitive domains. Overall, stronger correlations emerged for MPD and entropy than other DWI measures, although all correlations were in the expected direction. The strongest association was between DWI entropy and performance on the Symbol Digit Modalities Test, which assesses processing speed and working memory (r = -0.54). Fisher r to z transformations revealed that DWI, gray matter (GMF) and whole brain (BPF) atrophy, T1-lesion volume (LV) and T2-LV all accounted for similar amounts of variance in NP testing. Stepwise regression models determined whether multiple MRI measures predicted unique additive variance in test performance. GMF (R2 = 0.35, F =30.82, P <0.01) and entropy (ΔR2 =0.06, ΔF=5.47, P <0.05) both accounted for unique variance in processing speed. Our data make a stronger case for the clinical validity of DWI in MS than heretofore reported. DWI has very short acquisition times, and the segmentation method applied in the present study is reliable and fully automated. Given its overall simplicity and moderate correlation with cognition, DWI may offer several logistic advantages over more traditional MRI measures when predicting the presence of NP impairment. Multiple Sclerosis 2007; 13: 722-730. http://msj.sagepub.com
CD13/APN regulates endothelial invasion and filopodia formation
Authors: Petrovic Nenad , Schacke Wolfgang , Gahagan J. Reed , O'Conor Catherine A. , Winnicka Beata , Conway Rebecca E. , Mina-Osorio Paola , Shapiro Linda H.
Published: March 2007

CD13/aminopeptidase N is a transmembrane peptidase that is induced in the vasculature of solid tumors and is a potent angiogenic regulator. Here, we demonstrate that CD13 controls endothelial cell invasion in response to the serum peptide bradykinin by facilitating signal transduction at the level of the plasma membrane. Inhibition of CD13 abrogates bradykinin B2 receptor internalization, leading to the attenuation of downstream events such as bradykinin-induced activation of Cdc42 and filopodia formation, and thus affects endothelial cell motility. Investigation into mechanisms underlying this block led us to focus on B2R internalization via membrane-dependent mechanisms. Membrane disruption by depletion of cholesterol or trypsinization halts B2R internalization, invasion, and filopodia formation, which can be recovered with addition of cholesterol. However, this functional recovery is severely impaired in the presence of CD13 antagonists, and the distribution of membrane proteins is disordered in treated cells, suggesting a role for CD13 in plasma membrane protein organization. Finally, exogenous expression of wild-type but not mutant CD13 further alters protein distribution, suggesting peptidase activity is required for CD13's regulatory activity. Therefore, CD13 functions as a novel modulator of signal transduction and cell motility via its influence on specific plasma membrane organization, thus regulating angiogenesis.
CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells
Authors: Thedrez Aurelie , de Lalla Claudia , Allain Sophie , Zaccagnino Luca , Sidobre Stephane , Garavaglia Claudio , Borsellino Giovanna , Dellabona Paolo , Bonneville Marc , Scotet Emmanuel , Casorati Giulia
Published: March 2007

The CD4 coreceptor is crucial in the activation of major histocompatibility complex (MHC) class II restricted CD4 + T lymphocytes by binding the same MHC class as the T-cell receptor (TCR) and by potentiating TCR-dependent signaling. CD4 is also expressed by invariant natural killer T cells (iNKT), which recognize natural and synthetic lipid antigens, such as α-galactosyl ceramide (α-GalCer), in association with the MHC class I–like CD1d molecule. Human iNKT cells can be divided into 2 major subsets depending on CD4 expression: CD4 + iNKT preferentially produce T-helper (Th)0/Th2 cytokines, whereas CD4− iNKT cells produce Th1 cytokines after antigenic activation. Cytokines produced by iNKT may have immunomodulatory roles in various physiopathologic contexts, but their mode of regulation by iNKT cells remains ill-defined. Using blocking reagents neutralizing CD4 binding, experimental systems where MHC class II molecules are absent and recombinant α-GalCer/CD1d complexes, we show that CD4 potentiates human iNKT cell activation by engaging CD1d molecules. These results indicate that the CD4 coreceptors may contribute to the fine tuning of iNKT cells reactivity.
Stable trichimerism after marrow grafting from 2 DLA-identical canine donors and nonmyeloablative conditioning
Authors: Graves Scott S. , Hogan William , Kuhr Christian S. , Diaconescu Razvan , Harkey Michael A. , Georges George E. , Sale George E. , Zellmer Eustacia , Baran Szczepan W. , Jochum Christoph , Stone Brad , Storb Rainer
Published: March 2007

Although hematopoietic cell transplantation (HCT) is generally accomplished using a single donor, multiple donors have been used to enhance the speed of engraftment, particularly in the case of umbilical cord blood grafts. Here we posed the question in the canine HCT model whether stable dual-donor chimerism could be established using 2 DLA-identical donors. We identified 8 DLA-identical littermate triplets in which the marrow recipients received 2 Gy total body irradiation followed by marrow infusions from 2 donors and postgrafting immunosuppression. All 8 dogs showed initial “trichimerism,” which was sustained in 5 dogs, while 2 dogs rejected one of the allografts and remained mixed chimeras, and 1 dog rejected both allografts. Immune function in one trichimeric dog, as tested by mixed leukocyte culture response and antibody response to sheep red blood cells, was found to be normal. Five dogs received kidney grafts from one of their respective marrow donors at least 6 months after HCT without immunosuppressive drugs, and grafts in 4 dogs are surviving without rejection. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow grafts from 2 DLA-identical littermates could result in sustained trichimerism, and immunologic tolerance could include a kidney graft from one of the marrow donors.
Randomized Controlled Trial of Annual Zoledronic Acid to Prevent Gonadotropin-Releasing Hormone Agonist–Induced Bone Loss in Men With Prostate Cancer
Authors: Michaelson M. Dror , Kaufman Donald S. , Lee Hang , McGovern Francis J. , Kantoff Philip W. , Fallon Mary Anne , Finkelstein Joel S. , Smith Matthew R.
Published: March 2007

Purpose

Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Annual zoledronic acid increases BMD in postmenopausal women, but its efficacy in hypogonadal men is not known.

Patients and Methods

In a 12-month study, 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than −2.5 were randomly assigned to zoledronic acid (4 mg intravenously on day 1 only) or placebo. BMD of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry.

Results

Mean (± SE) BMD of the posteroanterior lumbar spine decreased by 3.1% ± 1.0% in men assigned to placebo and increased by 4.0% ± 1.0% in men assigned to zoledronic acid (P < .001). BMD of the total hip decreased by 1.9% ± 0.7% in men assigned to placebo and increased by 0.7% ± 0.5% in men assigned to zoledronic acid (P = .004). Similar between-group differences were observed for the femoral neck and trochanter. Serum N-telopeptide, a marker of osteoclast activity, decreased significantly after zoledronic acid treatment.

Conclusion

In men receiving a GnRH agonist, a single treatment with zoledronic acid significantly increased BMD and durably suppressed serum N-telopeptide levels for 12 months. Annual zoledronic acid may be a convenient and effective strategy to prevent bone loss in hypogonadal men.