bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise Training Improves Baroreflex Sensitivity Associated With Oxidative Stress Reduction in Ovariectomized Rats
Authors: Irigoyen Maria-Cláudia , Paulini Janaina , Flores Lucinar J. F. , Flues Karin , Bertagnolli Mariane , Dias Moreira Edson , Consolim-Colombo Fernanda , Belló-Klein Adriane , De Angelis Kátia
Published: September 2005

The protection from coronary events that young women have is sharply reduced at menopause. Oxidative stress and baroreflex sensitivity impairment of the circulation have been demonstrated to increase cardiovascular risk. On the other hand, exercise training has been indicated as a nonpharmacological treatment for many diseases. The aim of the present study was to test the hypothesis that exercise training can improve baroreflex sensitivity associated with reduction in oxidative stress in ovariectomized rats, an experimental model of menopause. Exercise training was performed on a treadmill for 8 weeks. Arterial pressure and baroreflex sensitivity, which were evaluated by tachycardic and bradycardic responses to changes in arterial pressure, were monitored. Oxidative stress was evaluated by chemiluminescence and superoxide dismutase and catalase antioxidant enzyme activities. Exercise training reduced resting mean arterial pressure (112±2 vs 122±3 mm Hg in the sedentary group) and heart rate (325±4 vs 356±12 bpm in the sedentary group) and also improved baroreflex sensitivity (tachycardic response, 63% and bradycardic response, 58%). Myocardium (25%) and gastrocnemius muscle (48%) chemiluminescence were reduced, and myocardial superoxide dismutase (44%) and gastrocnemius catalase (97%) activities were enhanced in trained rats in comparison with sedentary rats. Myocardium chemiluminescence was positively correlated with systolic arterial pressure (
r
=0.6) and inversely correlated with baroreflex sensitivity (tachycardic response,
r
=−0.8 and bradycardic response,
r
=−0.7). These results indicate that exercise training in ovariectomized rats improves resting hemodynamic status and reflex control of the circulation, probably associated with oxidative stress reduction, suggesting a homeostatic role for exercise training in reducing cardiovascular risk in postmenopausal women.
Electrophysiological Characteristics and Catheter Ablation in Patients With Paroxysmal Right Atrial Fibrillation
Authors: Lin Yenn-Jiang , Tai Ching-Tai , Kao Tsair , Tso Han-Wen , Huang Jin-Long , Higa Satoshi , Yuniadi Yoga , Huang Bien-Hsien , Liu Tu-Ying , Lee Pi-Chang , Hsieh Ming-Hsiung , Chen Shih-Ann
Published: September 2005

Background—

Catheter ablation of the right atrial (RA) substrate has had variable efficacy in curing paroxysmal atrial fibrillation (PAF), suggesting that RA substrate ablation can play an important role in the treatment of atrial fibrillation (AF) in some patients. The aim of this study was to investigate the electrophysiological characteristics and ablation strategy and its results in a specific group of patients with paroxysmal RA-AF.

Methods and Results—

The study population consisted of 13 patients (8 men; age, 64±15 years) with drug-refractory (2±1 drugs), frequent episodes of PAF. Provocation maneuvers did not reveal any ectopic beat–initiating AF. However, rapid atrial pacing easily induced AF. Activation mapping during sinus rhythm, atrial pacing, and AF was visualized by using a noncontact mapping system. Noncontact mapping revealed RA reentry (6 patients with single-loop circuits and 7 with double-loop circuits) with conduction through channels between lines of block, crista terminalis gaps, and the cavotricuspid isthmus, which could be identified during sinus rhythm and atrial pacing, resulting in fibrillatory conduction in other parts of the RA. The consistency of wavefront activation was confirmed by frequency analysis from equally distributed mapping sites in the RA. Short lines of ablation lesions were aimed at the conduction channels between the lines of block, crista terminalis gaps, and the cavotricuspid isthmus, resulting in bidirectional block. AF was eliminated in 11 (85%) of 13 patients, and those 11 patients with acute success were free of AF without any antiarrhythmic drugs during the long-term follow-up period (16±6 months).

Conclusions—

RA ablation still can cure selected patients with PAF. Linear ablation of the RA substrate guided by the electrophysiological characteristics of RA-AF is an effective approach for treating this specific group of patients with AF.
Simvastatin Therapy Normalizes Sympathetic Neural Control in Experimental Heart Failure
Authors: Gao Lie , Wang Wei , Li Yu-Long , Schultz Harold D. , Liu Dongmei , Cornish Kurtis G. , Zucker Irving H.
Published: September 2005

Background—

In a previous study, we showed that simvastatin (SIM) therapy normalized sympathetic outflow and cardiovascular reflex regulation in chronic heart failure (CHF). However, the precise neural and cellular pathways for these effects are unknown. We hypothesized that SIM exerts its beneficial effect on autonomic function in CHF by downregulating central angiotensin II (Ang II) and superoxide mechanisms.

Methods and Results—

Experiments were carried out on 36 male New Zealand White rabbits, 13 normal and 23 CHF. All rabbits were identically instrumented to record mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA). Echocardiography was used to monitor cardiac function. Reverse transcription–polymerase chain reaction, Western blotting, and lucigenin-enhanced chemiluminescence were used to measure gene expression of Ang II type 1 receptor and NAD(P)H oxidase subunits and NAD(P)H oxidase activity in the rostral ventrolateral medulla. Compared with the CHF control group, SIM significantly reduced the central Ang II–induced pressor and sympathoexcitatory responses, decreased baseline RSNA (57.3±3.2% to 22.4±2.1% of maximum,
P
<0.05), increased baroreflex control of heart rate (gain
max
, 1.6±0.3 to 4.5±0.2 bpm/mm Hg,
P
<0.05), and increased RSNA (gain
max
, 1.7±0.2% to 4.9±0.6% of maximum/mm Hg,
P
<0.01). Importantly, SIM improved left ventricular function (EF, 32.4±4.1% to 51.7±3.2%,
P
<0.05). SIM also downregulated mRNA and protein expression of Ang II type 1 receptor and NAD(P)H oxidase subunits and inhibited NAD(P)H oxidase activity in the rostral ventrolateral medulla of CHF rabbits. Chronic intracerebroventricular infusion of Ang II completely abolished the aforementioned effects of SIM in CHF rabbits.

Conclusions—

These data strongly suggest that SIM normalizes autonomic function in CHF by inhibiting central Ang II mechanisms and therefore the superoxide pathway. These data also demonstrate that SIM improves left ventricular function in pacing-induced CHF rabbits.
Isolated and Combined Tears of the Subscapularis Tendon
Authors: Kreuz Peter C. , Remiger Andreas , Erggelet Christoph , Hinterwimmer Stefan , Niemeyer Philipp , Gächter Andre
Published: September 2005

Background

Isolated and combined subscapularis tendon tears are rare and are described in the literature only in small numbers.

Hypothesis

The outcome of surgical intervention for isolated and combined subscapularis tendon tears may be influenced by the tear pattern of the anterior rotator cuff and the period of time between trauma and surgical procedure.

Study Design

Case series; Level of evidence, 4.

Methods

Between 1994 and 1999, 34 shoulders with isolated traumatic tears (16 shoulders) or subscapularis tendon rupture combined with a supraspinatus tendon tear were treated operatively. The average patient age was 51 years, and the mean follow-up period was 37 months. For statistical analyses, the Friedman and Mann-Whitney tests were used.

Results

In patients with isolated tears, the Constant score rose from an average of 43.9 to 88.7 points (P <. 01), and in patients with combined tears, it rose from an average of 40.6 to 74.7 points (P <. 01). Isolated tears improved 14 points more than combined tears (P <. 05). The delay between trauma and surgical intervention was inversely proportional to the improvement in the Constant score. The Spearman coefficient of correlation was -0.97 in isolated tears and -0.89 in combined tears.

Conclusions

Young patients with isolated traumatic tears of the subscapularis tendon and immediate repair have the best prognostic factors for treatment. Accuracy in the trauma history and the clinical and radiographic examination is demanded.
The Fate of Host and Graft Cells in Early Healing of Bone Tunnel after Tendon Graft
Authors: Kobayashi Masashi , Watanabe Nobuyoshi , Oshima Yasushi , Kajikawa Yoshiteru , Kawata Mitsuhiro , Kubo Toshikazu
Published: September 2005

Background

The behavior of host and graft cells during the healing process after autologous tendon graft has not been elucidated.

Hypothesis

Host cells will integrate into the bone-tendon interface and contribute to cellular repopulation of the graft.

Study Design

Controlled laboratory study.

Methods

Twelve-week-old, genetically identical, female green fluorescent protein transgenic rats (n = 20) and wild-type rats (n = 20) were used. The rats were divided into 2 experimental groups. In group A, the Achilles tendons of wild-type rats were harvested and transplanted into the transcondylar femoral bone tunnels of green fluorescent protein rats. In group B, the Achilles tendons of green fluorescent protein rats were transplanted into a transcondylar femoral bone tunnel of wild-type rats. Immediately after transplantation (time zero) and at 1, 2, and 4 weeks after the transplantation, distal femoral epiphyses were harvested and cut into 14-μm serial sagittal frozen sections. The sections were examined with a confocal laser-scanning microscope to quantify green fluorescent protein-positive cell survival.

Results

At time zero, only host cells in group A and only graft cells in group B demonstrated green fluorescent protein signals. At 1 week in group A, many green fluorescent protein-positive cells were found in the graft. In group B, a few green fluorescent protein-positive cells were found in the graft. At 2 and 4 weeks in group A, many green fluorescent protein-positive cells were detected in the graft, but green fluorescent protein-positive cells had disappeared completely in group B.

Conclusion

Host cells, rather than graft cells, contribute to repair of the bone-tendon interface and the remodeling of grafts after simulated autologous tendon graft.
Evaluation of a Cultural Competence Course
Authors: Brathwaite Angela E. Cooper
Published: September 2005

This study addressed the perceived lack of an integrated course with theoretical and experiential knowledge related to cultural competence for public health nurses (PHNs) and the importance of providing culturally competent services to clients. Mixed methods were used to examine the effectiveness of a course to increase 76 PHNs’ level of cultural competence. A one-group repeated measures design was used to ascertain the pattern of change in participants over time. The qualitative results complemented the quantitative findings, which were significant in relating to the five dimensions of Campinha-Bacote’s model of cultural competence.
Investigating Delay in Social Service Referral as a Predictor of Unattained Social Service Goals in Home Health Care
Authors: Dyeson Timothy B. , Watkins Corie , Jolly LaRue
Published: September 2005

The present study sought primarily to determine whether attainment of social service goals was affected by the number of days between admission to home care and referral to medical social services. We also sought to determine if patient residence in a rural or urban area, annual income, and the total number of social service goals affected attainment of social service goals. Using a random sample of 306 home care patients throughout Texas, we found that the length of time between admission to home care and social service referral and annual income did not have a significant effect on social service goal attainment. However, elders living in rural areas and those having a moderate number of social service goals had significantly more unattained social service goals. Social service implications are discussed.
Versatile and declarative dynamic programming using pair algebras
Authors: Steffen Peter , Giegerich Robert
Published: September 2005

Background

Dynamic programming is a widely used programming technique in bioinformatics. In sharp contrast to the simplicity of textbook examples, implementing a dynamic programming algorithm for a novel and non-trivial application is a tedious and error prone task. The algebraic dynamic programming approach seeks to alleviate this situation by clearly separating the dynamic programming recurrences and scoring schemes.

Results

Based on this programming style, we introduce a generic product operation of scoring schemes. This leads to a remarkable variety of applications, allowing us to achieve optimizations under multiple objective functions, alternative solutions and backtracing, holistic search space analysis, ambiguity checking, and more, without additional programming effort. We demonstrate the method on several applications for RNA secondary structure prediction.

Conclusion

The product operation as introduced here adds a significant amount of flexibility to dynamic programming. It provides a versatile testbed for the development of new algorithmic ideas, which can immediately be put to practice.
Rapid single nucleotide polymorphism mapping in C. elegans
Authors: Davis M Wayne , Hammarlund Marc , Harrach Tracey , Hullett Patrick , Olsen Shawn , Jorgensen Erik M
Published: September 2005

Background

InC. elegans, single nucleotide polymorphisms (SNPs) can function as silent genetic markers, with applications ranging from classical two- and three-factor mapping to measuring recombination across whole chromosomes.

Results

Here, we describe a set of 48 primer pairs that flank SNPs evenly spaced across theC. elegansgenome and that work under identical PCR conditions. Each SNP in this set alters aDraI site, enabling rapid and parallel scoring. We describe a procedure using these reagents to quickly and reliably map mutations. We show that these techniques correctly map a known gene,dpy-5. We then use these techniques to map mutations in an uncharacterized strain, and show that its behavioral phenotype can be simultaneously mapped to three loci.

Conclusion

Together, the reagents and methods described represent a significant advance in the accurate, rapid and inexpensive mapping of genes inC. elegans.
Attenuated Expression of DFFB is a Hallmark of Oligodendrogliomas with 1p-Allelic Loss
Authors: McDonald J Matthew , Dunmire Valerie , Taylor Ellen , Sawaya Raymond , Bruner Janet , Fuller Gregory N , Aldape Kenneth , Zhang Wei
Published: September 2005

Allelic loss of chromosome 1p is frequently observed in oligodendroglioma. We screened 177 oligodendroglial tumors for 1p deletions and found 6 tumors with localized 1p36 deletions. Several apoptosis regulation genes have been mapped to this region, includingTumor Protein 73 (p73),DNA Fragmentation Factor subunits alpha(DFFA) andbeta(DFFB), andTumor Necrosis Factor Receptor Superfamily Members 9and25(TNFRSF9, TNFRSF25). We compared expression levels of these 5 genes in pairs of 1p-loss and 1p-intact tumors using quantitative reverse-transcriptase PCR (QRTPCR) to test if 1p deletions had an effect on expression. Only theDFFBgene demonstrated decreased expression in all tumor pairs tested. Mutational analysis did not revealDFFBmutations in 12 tested samples. However, it is possible thatDFFBhaploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development.
Possibility of selection against mtDNA mutations in tumors
Authors: Khaidakov M , Reis RJ Shmookler
Published: September 2005

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.
Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats
Authors: Louter-van de Haar Johanna , Wielinga Peter Y , Scheurink Anton JW , Nieuwenhuizen Arie G
Published: September 2005

Background

Studies on the effects of (-)-hydroxycitric acid (HCA) in humans are controversial. As differences in the HCA preparations may contribute to this apparent discrepancy, the aim of the current study is to compare different HCA-containing preparations in adult Wistar rats.

Design

The effects of 3 different HCA-containing preparations (Regulator, Citrin K, Super CitriMax HCA-600-SXS, all used at an effective HCA dose of 150 and 300 mg/kg, administered intragastrically) on food intake and body weight were studied in adult male Wistar rats. The efficacy was tested under 2 different experimental conditions: 1) after a single dose administration and 2) during repeated administration for 4 subsequent days.

Results

Regulator and Citrin K significantly reduced food intake in both experimental setups, while Super CitriMax HCA-600-SXS was less effective. When administered for 4 subsequent days Regulator and Citrin K diminished body weight gain.

Conclusion

Regulator and Citrin K were shown to be potent inhibitors of food intake in rats, whereas Super CitriMax HCA-600-SXS showed only small and more inconsistent effects. The striking differences in efficacy between these 3 preparations indicate that low doses of a relatively low-effective HCA preparation may have contributed to the lack of efficacy as found in several human studies.
Inflammation causes tissue-specific depletion of vitamin B6
Authors: Chiang En-Pei , Smith Donald E , Selhub Jacob , Dallal Gerard , Wang Yi-Cheng , Roubenoff Ronenn
Published: September 2005

Previously we observed strong and consistent associations between vitamin B6 status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B6 levels. Such strong associations imply that impaired vitamin B6 status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B6 tissue contents and its excretion in vivo. A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B6 during acute and chronic inflammation. Patients with rheumatoid arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in significantly lower pyridoxal 5'-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B6. The low plasma pyridoxal 5'-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B6 excretion. Possible causes of decreased levels of vitamin B6 are discussed.
Selective estrogen receptor modulators inhibit growth and progression of premalignant lesions in a mouse model of ductal carcinoma in situ
Authors: Namba Ruria , Young Lawrence JT , Maglione Jeannie E , McGoldrick Erik T , Liu Stephenie , Wurz Gregory T , DeGregorio Michael W , Borowsky Alexander D , MacLeod Carol L , Cardiff Robert D , Gregg Jeffrey P
Published: September 2005

Introduction

Ductal carcinoma in situ (DCIS) is a noninvasive premalignant lesion and is considered a precursor to invasive carcinoma. DCIS accounts for nearly 20% of newly diagnosed breast cancer, but the lack of experimentally amenable in vivo DCIS models hinders the development of treatment strategies. Here, we demonstrate the utility of a mouse transplantation model of DCIS for chemoprevention studies using selective estrogen receptor modulators (SERMs). This model consists of a set of serially transplanted lines of genetically engineered mouse mammary intraepithelial neoplasia (MIN) outgrowth (MIN-O) tissue that have stable characteristics. We studied the ovarian-hormone-responsiveness of one of the lines with a particular focus on the effects of two related SERMs, tamoxifen and ospemifene.

Methods

The estrogen receptor (ER) status and ovarian-hormone-dependence of the mouse MIN outgrowth tissue were determined by immunohistochemistry and ovarian ablation. The effects of tamoxifen and ospemifene on the growth and tumorigenesis of MIN outgrowth were assessed at 3 and 10 weeks after transplantation. The effects on ER status, cell proliferation, and apoptosis were studied with immunohistochemistry.

Results

The MIN-O was ER-positive and ovarian ablation resulted in reduced MIN-O growth and tumor development. Likewise, tamoxifen and ospemifene treatments decreased the MIN growth and tumor incidence in comparison with the control (P < 0.01). Both SERMs significantly decreased cell proliferation. Between the two SERM treatment groups, there were no statistically significant differences in MIN-O size, tumor latency, or proliferation rate. In contrast, the ospemifene treatment significantly increased ER levels while tamoxifen significantly decreased them.

Conclusion

Tamoxifen and ospemifene inhibit the growth of premalignant mammary lesions and the progression to invasive carcinoma in a transplantable mouse model of DCIS. The inhibitory effects of these two SERMs are similar except for their effects on ER modulation. These differences in ER modulation may suggest different mechanisms of action between the two related SERMs and may portend different long-term outcomes. These data demonstrate the value of this model system for preclinical testing of antiestrogen or other therapies designed to prevent or delay the malignant transformation of premalignant mammary lesions in chemoprevention.
Hospital-acquired sinusitis is a common cause of fever of unknown origin in orotracheally intubated critically ill patients
Authors: van Zanten Arthur RH , Dixon Mark J , Nipshagen Martine D , de Bree Remco , Girbes Armand RJ , Polderman Kees H
Published: September 2005

Introduction

Sinusitis is a well recognised but insufficiently understood complication of critical illness. It has been linked to nasotracheal intubation, but its occurrence after orotracheal intubation is less clear. We studied the incidence of sinusitis in patients with fever of unknown origin (FUO) in our intensive care unit with the aim of establishing a protocol that would be applicable in everyday clinical practice.

Methods

Sinus X-rays (SXRs) were performed in all patients with fever for which an initial screening (physical examination, microbiological cultures and chest X-ray) revealed no obvious cause. All patients were followed with a predefined protocol, including antral drainage in all patients with abnormal or equivocal results on their SXR.

Results

Initial screening revealed probable causes of fever in 153 of 351 patients (43.6%). SXRs were taken in the other 198 patients (56.4%); 129 had obvious or equivocal abnormalities. Sinus drainage revealed purulent material and positive cultures (predominantly Pseudomonas and Klebsiella species) in 84 patients. Final diagnosis for the cause of fever in all 351 patients based on X-ray results, microbiological cultures, and clinical response to sinus drainage indicated sinusitis as the sole cause of fever in 57 (16.2%) and as contributing factor in 48 (13.8%) patients with FUO. This will underestimate the actual incidence because SXR and drainage were not performed in all patients.

Conclusion

Physicians treating critically ill patients should be aware of the high risk of sinusitis and take appropriate preventive measures, including the removal of nasogastric tubes in patients requiring long-term mechanical ventilation. Routine investigation of FUO should include computed tomography scan, SXR or sinus ultrasonography, and drainage should be performed if any abnormalities are found.
Preferences for place of care and place of death among informal caregivers of the terminally ill
Authors: Brazil Kevin , Howell Doris , Bedard Michel , Krueger Paul , Heidebrecht Christine
Published: September 2005

Objectives: (1) To determine informal caregivers perceptions about place of care and place of death; and (2) to identify variables associated with a home death among terminally ill individuals who received in–home support services in a publicly funded home care system.

Participants and design: A total of 216 informal caregivers participated in a bereavement interview. Data collection included care recipient and informal caregiver characteristics, the use of and satisfaction with community services, and preferences about place of death.

Results: Most caregivers reported that they and the care recipient had a preferred place of death (77 and 68%, respectively) with over 63% reporting home as the preferred place of death. Caregivers had a greater preference for an institutional death (14%) than care recipients (4.7%). While 30% of care recipients did not die in their preferred location, most caregivers (92%) felt, in retrospect, that where the care recipient died was the appropriate place of death. Most caregivers reported being satisfied with the care that was provided. The odds of dying at home were greater when the care recipient stated a preference for place of death (OR: 2.92; 95% CI: 1.25, 6.85), and the family physician made home visits during the care recipients last month of life (Univariate odds ratios (OR): 4.42; 95% CI: 1.46, 13.36).

Discussion: The ethic of self–control and choice for the care recipient must be balanced with consideration for the well being of the informal caregiver and responsiveness of the community service system.
A validation study of a pain classification system for advanced cancer patients using content experts: the Edmonton Classification System for Cancer Pain
Authors: Nekolaichuk Cheryl L , Fainsinger Robin L , Lawlor Peter G
Published: September 2005

The purpose of this study was to gather construct validity evidence for a pain classification system for advanced cancer patients using content experts. Two expert panels, representing regional (Panel A, n / 18) and national/international (Panel B, n / 52) palliative medicine and pain specialists, were purposefully selected to participate in a modified Delphi survey technique, to evaluate an existing pain classification system, the Revised Edmonton Staging System (rESS). Each panel participated in two survey rounds, with response rates of 67% (Panel A, Round 1), 39% (Panel A, Round 2), 56% (Panel B, Round 1) and 64% (Panel B, Round 2). The rESS consists of five features: mechanism of pain, incidental pain, psychological distress, addictive behavior and cognitive function. Most participants either agreed or strongly agreed with including the five existing rESS features in a pain classification system, ranging from 67% (Panel A, cognitive function) to 100% (Panel B, mechanism of pain). Most participants suggested keeping the current definitions for these features, with some revisions. Based on participant feedback, definitions for incidental pain, psychological distress, addictive behavior and cognitive function were revised, including the development of guidelines for use. To reflect its intended use as a classification system, the name of the instrument was changed to the Edmonton Classification System for Cancer Pain (ECS-CP).
Challenging the framework for evidence in palliative care research
Authors: Aoun Samar M , Kristjanson Linda J
Published: September 2005

This paper examines the debate about best evidence within the public health literature and proposes that similar arguments and concerns exist with respect to use of current evidence-based approaches to implementing research and evaluating the literature in palliative care. Whilst randomized controlled trials (RCTs) remain the gold standard and are appropriate in many instances of palliative care research, there is a need for an alternate research design framework that incorporates contextual and compositional effects pertinent to palliative care research. A framework, entitled Equity-Based Evidence, is discussed as an approach to evidence-based knowledge development in palliative care.
Assessing Benefit and Risk in the Prevention of Prostate Cancer: The Prostate Cancer Prevention Trial Revisited
Authors: Klein Eric A. , Tangen Catherine M. , Goodman Phyllis J. , Lippman Scott M. , Thompson Ian M.
Published: September 2005

Purpose

The Prostate Cancer Prevention Trial demonstrated a 25% reduction in period prevalence of prostate cancer in men randomly assigned to 5 mg/d of finasteride. However, widespread use of finasteride for prevention is inhibited by the observed increased risk of high-grade disease. We present a model of risk and benefit that estimates the potential effects of histologic artifact in the assignment of excess risk for high-grade disease and the possible effect of overdetection bias introduced by finasteride-induced volume reduction.

Methods

The absolute benefit/absolute risk ratio of finasteride use was estimated by calculating the ratio of absolute risk reduction in the finasteride arm to the absolute risk of excess high-grade cancers. This ratio was recalculated for assumptions that 10%, 25%, or 50% of the excess high-grade cancers were due to histologic artifact, and that there was a 25% overdetection bias in the finasteride arm.

Results

For all cancers the absolute benefit/absolute risk ratio increased from 4.6:1 to 5.1:1, 6.2:1, and 9.2:1 for assumptions of 10%, 25%, or 50% histologic artifact, respectively. The ratio increased from 4.6:1 to 8.2:1 for the assumption of 25% overdetection bias, and to 9.1:1, 10.9:1, and 16.3:1 for combined assumptions of 25% overdetection bias and 10%, 25%, or 50% histologic artifact, respectively.

Conclusion

The adoption of a prevention strategy hinges on potential benefits weighed against potential risks. This model demonstrates the magnitude of effect for a hypothesized range of histologic artifact and overdetection bias on the assessment of risk versus benefit for finasteride.
Assessment of Quality of Life in the Supportive Care Setting of the Big Lung Trial in Non–Small-Cell Lung Cancer
Authors: Brown J. , Thorpe H. , Napp V. , Fairlamb D.J. , Gower N.H. , Milroy R. , Parmar M.K.B. , Rudd R.M. , Spiro S.G. , Stephens R.J. , Waller D. , West P. , Peake M.D.
Published: September 2005

Purpose

The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non–small-cell lung cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards.

Patients and Methods

EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks.

Results

A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks.

Conclusion

There were no important adverse effects of chemotherapy on QoL.
Assessment of Quality of Life in MA.17: A Randomized, Placebo-Controlled Trial of Letrozole After 5 Years of Tamoxifen in Postmenopausal Women
Authors: Whelan Timothy J. , Goss Paul E. , Ingle James N. , Pater Joseph L. , Tu Dongsheng , Pritchard Kathleen , Liu Shifang , Shepherd Lois E. , Palmer Michael , Robert Nicholas J. , Martino Silvana , Muss Hyman B.
Published: September 2005

Purpose

To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial.

Methods

Patients completed the Short Form 36-item Health Survey (SF-36) and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline, 6 months, and annually. Mean change scores from baseline were compared between groups for summary measures and domains. A response analysis compared the proportion of patients who demonstrated an important change in QOL.

Results

Of 5,187 randomly assigned women in the trial, 3,612 (69.9%) participated in the QOL substudy: 1,799 were allocated to placebo and 1,813 were allocated to letrozole. No differences were seen between groups in mean change scores from baseline for the SF-36 physical and mental component summary scores at 6, 12, 24, and 36 months. Small (< 0.2 standard deviations) but statistically significant differences in mean change scores from baseline were seen for the SF-36 domains of physical functioning (12 months), bodily pain (6 months) and vitality (6 and 12 months), and the MENQOL vasomotor (6, 12, and 24 months) and sexual domains (12 and 24 months). On the response analysis, a significant difference was seen between groups for the bodily pain domain (percentage of patients reporting a worsening of QOL, 47% placebo v 51% letrozole; P = .009) and the vasomotor domain (22% placebo v 29% letrozole; P = .001).

Conclusion

Letrozole did not have an adverse impact on overall QOL. Small effects were seen in some domains consistent with a minority of patients experiencing changes in QOL compatible with a reduction in estrogen synthesis.
Outcome of Shunting in Idiopathic Normal-pressure Hydrocephalus and the Value of Outcome Assessment in Shunted Patients
Authors: Klinge Petra , Marmarou Anthony , Bergsneider Marvin , Relkin Norman , Black Peter McL.
Published: September 2005

OBJECTIVE:

To develop guidelines for assessing shunt outcome in patients with idiopathic normal-pressure hydrocephalus (INPH). To date, the literature available on this topic has been marked by disparate definitions of clinical improvement, varying postoperative follow-up protocols and periods, and substantial differences in the postoperative management. Because specific criteria for defining clinical improvement are seldom reported, conclusions drawn about shunt outcome may be subjective.

METHODS:

A MEDLINE search back to 1966 was undertaken using the query NPH, normal-pressure hydrocephalus, shunting, shunt treatment, shunt response, outcome, and clinical outcome. The criteria for selection were studies that included INPH from 1966 to the present in which the outcome of INPH was reported in patient groups of 20 or more.

RESULTS:

To date, there is no standard for outcome assessment of shunt treatment in INPH. The variable improvement rates reported are not only because of different criteria for selection of patients but also because of different postoperative assessment procedures and follow-up intervals.

CONCLUSION:

Studies that have established fixed protocols for follow-up have shown that short- and long-term periods after shunting are determined by many factors. Whereas short-term results were more likely to be influenced by shunt-associated risks, long-term results were independent of factors inherent to the shunt procedure and shunt complications, i.e., death and morbidity related to concomitant cerebrovascular and vascular diseases. Studies have shown that beyond 1 year after surgery, these factors definitely influence the clinical effect of shunting, making the 1-year postshunt period a potential determinant of the shunt outcome. Guidelines for outcome assessment were developed on the basis of the available evidence and consensus of expert opinion.
Emerging Concepts in the Treatment of Intracranial Aneurysms: Stents, Coated Coils, and Liquid Embolic Agents
Authors: Lanzino Giuseppe , Kanaan Yassine , Perrini Paolo , Dayoub Hayan , Fraser Kenneth
Published: September 2005

ENDOVASCULAR TECHNIQUES FOR the treatment of intracranial aneurysms are rapidly evolving. Modifications of more traditional coils have been introduced. Such modifications include newer coils coated with various polymers to increase both coil thrombogenicity and degree of aneurysm packing. In addition, newer coil designs aimed at improving the conformability of the coil to the aneurysm have been used with promising preliminary results. The availability of a newer generation of stents specifically designed for intracranial navigation allows for more effective treatment of aneurysms with wide necks, which usually have been considered unsuitable for optimal endovascular treatment. Endovascular alternatives to coil embolization, such as liquid embolic materials, also have been explored for the treatment of intracranial aneurysms, with varying results. We summarize the rationale for use of these newer devices and early clinical experiences. Areas of current research and future directions of endovascular aneurysm treatment also are discussed.
In Vivo Optical Spectroscopy Detects Radiation Damage in Brain Tissue
Authors: Lin Wei-Chiang , Mahadevan-Jansen Anita , Johnson Mahlon D. , Weil Robert J. , Toms Steven A.
Published: September 2005

OBJECTIVE:

Magnetic resonance imaging abnormalities in malignant brain tumors after irradiation may represent either recurrent tumor or radiation injury. Optical spectroscopy may represent a novel technique to identify radiation damage in brain tissues and to differentiate contrast-enhancing lesions from recurrent tumor.

METHODS:

Fluorescence and diffuse reflectance spectra were acquired from 90 patients: 15 undergoing surgical resection for presumed recurrent tumor after radiation therapy, 15 with epilepsy and hippocampal sclerosis, and 60 with tumors who had not received irradiation. Optical spectra were acquired from 6 to 10 sites and were compared with a biopsy obtained from beneath the optical spectroscopy probe; the data then were classified by a neuropathologist blinded to the spectroscopy data. A probe for the intraoperative collection of diffuse reflectance and fluorescence spectra was used.

RESULTS:

Thirteen of 15 patients (29 of 129 spectra) with previous irradiation showed a unique spectral feature characterized by a fluorescence peak centered at 500 nm (F500). All biopsy specimens showing histopathological signs of radiation injury had the F500 on their corresponding spectra (18 of 18). The F500 was identified in another 10% (11 of 111 spectra) of samples with previous irradiation but no histologically identifiable signs of radiation damage. The F500 was never seen in the normal temporal lobe of epilepsy patients with hippocampal sclerosis (0 of 105) and was seen in only 1.5% of tumor patients who did not undergo previous irradiation (6 of 433).

CONCLUSION:

Optical spectroscopy detects radiation damage in brain tissues. The F500 spectral peak may allow accurate selection of tissues for biopsy in evaluating patients with new, contrast-enhancing lesions in the setting of previous irradiation.
Altered Flow Territories after Extracranial-Intracranial Bypass Surgery
Authors: Hendrikse Jeroen , van der Zwan Albert , Ramos Lino M.P. , van Osch Matthias J.P. , Golay Xavier , Tulleken Cees A.F. , van der Grond Jeroen
Published: September 2005

OBJECTIVE:

To prevent stroke after carotid sacrifice and to augment cerebral perfusion in patients with internal carotid artery (ICA) occlusion, high-flow extracranial-intracranial (EC-IC) bypass operations are performed. Although the function and efficacy of the bypass is monitored during surgery, the postoperative flow through the bypass is significantly lower than the flow in the contralateral ICA. Thus far, it is unknown whether decreased bypass flow is caused by a low tissue perfusion or by a relatively small flow territory.

METHODS:

Seven patients, four with an atherosclerotic ICA occlusion and three with a giant aneurysm of the ICA, were investigated; each underwent a high-flow EC-IC bypass and permanent occlusion of the ICA. Cerebral blood flow was measured with arterial spin labeling perfusion magnetic resonance imaging. Separate flow territory mapping of the EC-IC bypass, contralateral ICA, and posterior circulation was performed with selective arterial spin labeling magnetic resonance imaging.

RESULTS:

No significant difference was found in cerebral blood flow between the hemisphere ipsilateral to the EC-IC bypass (70.9 ± 11.3 ml/min/100 g tissue), contralateral to the EC-IC bypass (71.9 ± 14.3 ml/min/100 g tissue), and comparable findings in 50 healthy control participants (69.1 ± 17.5 ml/min/100 g tissue). Paired analysis of the individual flow territories demonstrated a 15% volume reduction (P = 0.018) in flow territory of the EC-IC bypass compared with the contralateral side.

CONCLUSION:

In the present study, we demonstrate the feasibility of selective arterial spin labeling magnetic resonance imaging for clinical follow-up of patients after high-flow EC/IC bypass surgery, providing both information on flow territories and the level of regional cerebral blood flow.
Avulsion Fracture of the Foramen Magnum Treated with Occiput-to-C1 Fusion: Technical Case Report
Authors: Maughan Peter H. , Horn Eric M. , Theodore Nicholas , Feiz-Erfan Iman , Sonntag Volker K.H.
Published: September 2005

OBJECTIVE AND IMPORTANCE:

A 31-year-old woman presented with an avulsion fracture of the foramen magnum via bilateral occipital condyles with extension through the inferior aspect of the clivus.

CLINICAL PRESENTATION:

The patient had no neurological deficits and was initially immobilized in a halo brace.

INTERVENTION:

To preserve rotational motion at C1–C2, we performed an occiput-to-C1 fusion with bilateral C1 lateral mass screws attached with rods to occipital keel screws. Postoperatively, the patient remained neurologically intact. Three-month follow-up imaging revealed no abnormal motion. Follow-up computed tomographic scan showed an intact construct and bony fusion.

CONCLUSION:

This rare injury, a bony variant of occipitoatlantal dislocation, was successfully treated with a unique occiput-to-C1 fusion.
Paraplegia after Tethered Cord Surgery: An Uncommon Combined Anomaly of Spinal Arteriovenous Fistula and Sacral Lipoma— Case Report
Authors: Cheung Arnold C. , Kalkanis Steven N. , Ogilvy Christopher S.
Published: September 2005

OBJECTIVE AND IMPORTANCE:

The coexistence of spinal arteriovenous malformation (AVM) with congenital abnormalities is relatively common. However, the association of a spinal AVM and lipoma is rare. We present an adult patient with this combined anomaly and discuss the clinical relevance of this case.

CLINICAL PRESENTATION:

A 42-year-old Caucasian man with progressive paraparesis initially underwent surgery for a tethered spinal cord. Postoperatively, he became paraplegic. He improved gradually over an interval of 8 months and, at that point, worsened again. Subsequent angiographic study revealed a spinal dural arteriovenous fistula located at S1–S2. Additionally, an occipital dural AVM was discovered near the transverse sinus.

INTERVENTION:

The spinal arteriovenous fistula was excised along with the sacral lipoma. The occipital arteriovenous fistula was embolized successfully at a later time.

CONCLUSION:

The patient had immediate improvement in sensory symptoms after surgery. At a 9 month follow-up examination, he had regained the ability to walk with crutches, but his bladder dysfunction persisted. Recognition of co-existing vascular anomalies, such as spinal AVMs, is important in patients with tethered cords. The mechanisms involved in this patient's worsening neurological condition after release of the tethered cord are discussed.
Positron Emission Tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus Magnetic Resonance Imaging in the Diagnosis of Recurrent Gliomas
Authors: Rachinger Walter , Goetz Claudia , Pöpperl Gabriele , Gildehaus Franz Josef , Kreth Friedrich Wilhelm , Holtmannspötter Markus , Herms Jochen , Koch Walter , Tatsch Klaus , Tonn Jörg-Christian
Published: September 2005

OBJECTIVE:

New treatment modalities are available for patients with glioma, which may lead to unspecific changes in posttherapeutic magnetic resonance imaging (MRI) findings. Differentiation between tumor- and therapy-associated contrast enhancement on MRI scans after treatment may be difficult. The aim of this study was to analyze the diagnostic value of O-(2-[18F]fluoroethyl)-l-tyrosine (FET)-positron emission tomography (PET) and MRI in the detection of tumor recurrence in patients with glioma after radiotherapy, radiosurgery, or multimodal treatment.

METHODS:

The study included 36 patients with gliomas and neuroradiological diagnosis of tumor recurrence and 9 patients who had undergone radioimmunotherapy. Patients were consecutively treated between September 2001 and May 2003. A contemporary FET-PET investigation was performed in all patients. A tissue diagnosis was made for comparative analysis in all patients with progressive neuroradiological or clinical findings (32 of 45 patients). In patients with transient neuroradiological or clinical deterioration (13 of 45 patients), clinical follow-up was used to support or contradict the imaging-based diagnosis.

RESULTS:

Tumor recurrence was documented in 31 of 45 patients, and 14 of 45 patients were tumor free. FET-PET and MRI revealed a correct diagnosis in 44 and 36 patients, respectively. The difference was statistically significant (P < 0.01). Concordant findings after MRI and FET-PET were documented in 37 patients and discordant findings in 8 patients. The difference was statistically significant (P < 0.01). Specificity of FET-PET was 92.9%, and sensitivity was 100% (in patients suspected of having recurrent tumor as revealed by MRI). Sensitivity of MRI was 93.5%, and specificity was 50% (P < 0.05).

CONCLUSION:

For patients with gliomas undergoing multimodal treatment or various forms of irradiation, conventional follow-up with MRI is insufficient to distinguish between benign side effects of therapy and tumor recurrence. FET-PET is a powerful tool to improve the differential diagnosis in these patients.