bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-Registration of the Schaltenbrand-Wahren Microseries with the Probabilistic Functional Atlas
Authors: Nowinski Wieslaw L.
Published: October 2004

Objective: The Schaltenbrand-Wahren atlas (SWA) is anatomical, sparse and inconsistent in three dimensions. A high-resolution, electrophysiology-based atlas derived from numerous specimens overcomes these limitations. A combined anatomy-physiology atlas leverages the strengths and complementarity of both, which is studied here. Method: An electronic version of the SWA was constructed. A probabilistic functional atlas (PFA) was developed from electrophysiological and neuroimaging data with 0.25 mm3 resolution. A combined atlas is constructed by co-registering the PFA with the SWA by applying linear scaling along the intercommissural distance and the height of the thalamus. Results: An anatomy-physiology atlas is superior to its component atlases. When in register, the anatomical and functional atlases are displayed together and used simultaneously. A structure of interest from the PFA can be displayed with high resolution, compensating for its sparseness in the SWA, while its surrounding structures are obtained from the SWA. The best anatomical and functional targets can be compared: for the subthalamic nucleus, the horizontal and lateral coordinates of the SWA-based and PFA- based targets are approximately the same, while the latter is located 1.3–1.5 mm more anteriorly. Conclusion: An anatomy-physiology atlas may enhance the accuracy of targeting and increase the neurosurgeon’s confidence. It also opens new research avenues to serve as a reference for: (1) constructing an extendable atlas by adding new electrophysiological data, (2) comparing anatomical and functional targets, (3) studying and comparing various symptoms, and (4) comparing image-based targets obtained from various modalities.
Safety and Efficacy of Tiered Limited-Dose Gamma Knife Stereotactic Radiosurgery for Unilateral Acoustic Neuroma
Authors: Landy Howard J. , Markoe Arnold M. , Wu Xiaodong , Patchen Sherri J. , Reis Isildinha M. , Takita Cristiane , Abdel-Wahab May M. , Wen B-Chen , Wolfson Aaron H. , Huang David T.
Published: October 2004

Stereotactic radiosurgery has become a more widely employed modality of treatment for acoustic neuromas, but controversy still arises regarding the safety and efficacy of the technique. In general, radiation doses have been reduced over time. Since beginning treatments of acoustic neuromas with the Gamma Knife at the University of Miami/Jackson Memorial Medical Center in 1994, a dose regimen was adopted by the first author employing limited doses selected on the basis of tumor size with the anterior and medial regions of the prescription isodose surface kept just inside the gadolinium-enhanced limit of the tumor, in order to protect the facial nerve and brainstem. The records of patients treated for unilateral tumors were retrospectively reviewed. Fifty-two patients, aged 23–83 years, were treated with peripheral tumor doses of 10–14 Gy at the 45–70% isodoses. No patient developed new facial weakness or sensory loss; 3 patients had minor transient facial twitching within a few months of treatment. Of 34 patients followed more than 1 year (range 14–100 months, mean 43.4 months, median 37 months), 17 tumors reduced in size, 16 remained unchanged, and 1 increased in size. One patient, who had radiosurgery as planned postoperative adjuvant treatment after partial resection of a large tumor, developed an enlarging peritumoral arachnoid cyst that required surgical resection 79 months after radiosurgery. Patients with good pretreatment hearing retained approximately the same subjective level of hearing. Very good control of unilateral acoustic neuroma has been achieved by a limited-dose scheme that produces minimal complications, but due to the frequently indolent course of these tumors, continued long-term monitoring will be necessary.
Unilateral Battery Depletion in Parkinson’s Disease Patients Treated with Bilateral Subthalamic Nucleus Deep Brain Stimulation May Require Urgent Surgical Replacement
Authors: Chou Kelvin L. , Siderowf Andrew D. , Jaggi Jurg L. , Liang Grace S. , Baltuch Gordon H.
Published: October 2004

We describe 2 patients with advanced Parkinson’s disease (PD) treated with bilateral deep brain stimulation of the subthalamic nucleus in whom unilateral stimulator battery depletion resulted in the rapid appearance of disabling PD symptoms (severe rigidity, bradykinesia and gait difficulty). Both patients did not respond to high doses of dopaminergic medications and were restored to their previous level of function only with battery replacement. One patient developed a deep vein thrombosis and pulmonary emboli as a result of prolonged immobility. Although extreme worsening of PD secondary to battery depletion may be rare, such patients should have their stimulators replaced promptly.
Robotics in Colorectal Surgery
Authors: Hance J. , Rockall T. , Darzi A.
Published: October 2004

Minimally invasive surgery has been shown to offer many advantages to general surgical patients but has not been widely adopted for colorectal disease. Initial fears surrounding the oncological safety of laparoscopic colectomies have largely subsided but the technical challenges still remain. Surgical robots or telemanipulators present the laparoscopic surgeon with unrivaled dexterity and vision, which may allow colonic resections to be completed with greater ease. Although initial studies suggest promising results using currently available systems, it will take further time for patient benefits to be proven, therefore justifying the greater expense of operating with this new technology.
Strategies for Palliative Care in Advanced Colorectal Cancer
Authors: Dixon Matthew R. , Stamos Michael J.
Published: October 2004

Palliative care has appropriately been receiving increased attention in recent years. From the surgeon’s standpoint, therapy is considered palliative when resection of all known tumor sites is no longer possible or advisable. Since a cure, as commonly defined, is not possible, the goal of treatment and eventually the success of therapy becomes judged by the control of symptoms and alleviation of suffering. Providing optimal palliative care for the patient with advanced colorectal cancer is a complex and challenging process. The process of providing palliative care may be a departure from the traditional surgical satisfaction derived from the complete excision of a malignancy, but surgeons achieving excellence in palliative care will likely find this a rewarding endeavor.
Impact of Choice of Therapeutic Strategy for Acute Cholecystitis on Patient’s Health-Related Quality of Life
Authors: Johansson Mikael , Thune Anders , Blomqvist Anne , Nelvin Leif , Lundell Lars
Published: October 2004

Background: The aim of this prospective, randomized study was to determine if health related quality of life is affected by the choice of surgical strategy in the management of acute cholecystitis. Material and Methods: After diagnostic workup, patients were randomized to one of two groups: (1) early laparoscopic cholecystectomy (i.e. within 7 days after onset of symptoms) or (2) initial conservative treatment followed by delayed laparoscopic cholecystectomy. Seventy-four patients entered the early operation group and 71 patients were assigned to the delayed operation strategy. Assessments of quality of life were made at 1, 3 and 6 months after surgery, and in the delayed operation group also one month after the initial conservative treatment. Results: The gastrointestinal symptom scores were significantly better in three dimensions (diarrhea, indigestion, abdominal pain) one month after surgery for the acute operation group (p < 0.01). Three and 6 months after the operation we were unable to detect any significant differences between the groups. The patients in the delayed operation group did not appear to suffer from more symptoms in the period of time waiting for their elective operation. Psychological general well-being showed no major differences between the groups. Conclusion: Cholecystectomy in the acute phase of acute cholecystitis offers a significant reduction of gastrointestinal symptoms during the first postoperative month and to that associated improved quality of life in this group of patients.
Cushing’s Syndrome: Adrenalectomy and Long-Term Results
Authors: Meyer Andreas , Behrend Matthias
Published: October 2004

Background: The objective of this study was to assess the preoperative symptoms, intra- and postoperative complications and follow-up in patients after uni- or bilateral adrenalectomy due to Cushing’s syndrome (CS), independent of etiology. Methods: Clinical charts of 42 patients (5 with ACTH-dependent, 37 with ACTH-independent CS) were reviewed, and follow-up data were obtained from re-examination of the patients. Results: The symptoms most frequently seen were hypertension, changes of the skin and obesity. Eight bilateral and 36 unilateral adrenalectomies were carried out without any intraoperative complications. Postoperative complications occurred in 5 patients, 1 patient died on the fourth postoperative day. After a mean duration of 4.6 years 28 of 41 patients could be re-examined, 5 patients had died. One patient showed recurrence 4.3 years after unilateral adrenalectomy due to nodular hyperplasia, contralateral adrenalectomy again revealed nodular hyperplasia. Conclusion: Early diagnosis is essential in order to decrease the rate of pre-, intra- and postoperative complications. Endoscopic approach should be taken in a specialized center due to poor patient’s condition. Recurrent disease on the contralateral side may represent bilateral adrenal hyperplasia with sequential tumor formation, demonstrating the importance of extensive preoperative biochemical and imaging testing and close follow-up.
In situ Characterization of Gonadotropin- Releasing Hormone-I, -III, and Glutamic Acid Decarboxylase Expression in the Brain of the Sea Lamprey, Petromyzon marinus
Authors: Root Adam R. , Nucci Nathaniel V. , Sanford Jocelyn D. , Rubin Beverly S. , Trudeau Vance L. , Sower Stacia A.
Published: October 2004

The distribution of lamprey gonadotropin-releasing hormone (GnRH)-I and -III has been extensively characterized by immunocytochemistry in the forebrain of the sea lamprey, Petromyzon marinus. However, the cellular location of lamprey GnRH-III mRNA expression by in situ hybridization in the lamprey brain has not been determined. We show for the first time the location of expression of lamprey GnRH-III, as well as provide a more comprehensive in situ study of lamprey GnRH-I and glutamic acid decarboxylase (GAD; GABA-synthesizing enzyme) mRNA expression in the brain of the lamprey in different reproductive life stages. Colorimetric and dual-label fluorescent amplification methods of in situ hybridization were used on brain tissue sections of adult, juvenile, and larval sea lamprey. In each life stage of the lamprey, expression of lamprey GnRH-I was shown in the preoptic area (POA) and the hypothalamus forming the characteristic arc-like cell population extending from the preoptic nucleus (NPO) to the neurohypophysis. Lamprey GnRH-III expression was also seen in the POA of each life stage in close proximity to lamprey GnRH-I mRNA containing neurons. GAD expression was shown in distinct cell clusters in and around the POA, in the olfactory bulb, in the dorsal thalamus beneath the habenular region, and also in the ventral-medial hypothalamus stretching from the periventricular region to the anterior portion of the rhombencephalon. Using dual-label in situ hybridization, we have shown that lamprey GnRH-I and -III mRNA are colocalized in the same cells in the POA in adult lampreys. Dual-label in situ hybridization also showed close proximity of GAD mRNA containing neurons and GnRH containing neurons in the POA. These data suggest that γ-aminobutyric acid (GABA) may directly affect GnRH release in the brain of the sea lamprey.
Neonatal Hyperthyrotropinemia in Gestational Diabetes mellitus and Perinatal Complications
Authors: Leung Wing Cheong , Chan Karen K.L. , Lao Terence T.
Published: October 2004

The aim of this study is to explore the relationship between high cord blood thyroid-stimulating hormone (TSH) level and in-utero stress to the fetus in gestational diabetes mellitus (GDM). Cord blood TSH results were analyzed in 1,578 euthyroid infants from singleton pregnancies with GDM: 103 with elevated TSH (>16 mIU/l) and 1,475 with normal TSH. Maternal characteristics, pregnancy outcome and perinatal complications were compared between the two groups. Multiple logistic regression was used to study the association between high cord blood TSH level and various perinatal complications which reflect in-utero stress in GDM after adjusting for the confounding effects of parity, instrumental delivery, cesarean section and baby gender. High cord blood TSH level was found to be associated with the 1-min Apgar score <7 (OR 3.31, 95% CI 1.78–6.16), birth trauma (OR 3.44, 95% CI 1.11–10.69), neonatal jaundice requiring treatment (OR 2.08, 95% CI 1.30–3.32), neonatal sepsis (OR 2.34, 95% CI 1.24–4.42), respiratory complications (OR 3.45, 95% CI 1.37–8.70), neurological complications (OR 8.01, 95% CI 1.91–33.60) and overall perinatal morbidity (OR 2.41, 95% CI 1.58–3.67). Cord blood TSH level seems to be a better and independent indicator of the in-utero stress to the fetus in GDM when compared to the commonly used sugar profile result and HbA1c level.
Prior Heat Acclimation Confers Protection against Noise-Induced Hearing Loss
Authors: Paz Ziv , Freeman Sharon , Horowitz Michal , Sohmer Haim
Published: October 2004

Exposure to intense noise stress can cause a permanent noise-induced hearing loss which is thought to be due to elevation of reactive oxygen species in excess of the inherent antioxidant mechanisms of the cell. However, preconditioning to low levels of stress of one type can activate cellular mechanisms leading to the elevation of antioxidant levels so that the cell is then better able to tolerate subsequent severe stress of a different type. This has been called cross-tolerance. Here, we tested this hypothesis by acclimating rats to a moderate heat stress (30 days at 34°C). The rats were exposed to 113 dB SPL noise for 3 days (12 h/day) in three different groups: heat acclimated then noise exposed; noise exposed and then heat acclimated; heat acclimated, then noise exposed and then heat acclimated again. Permanent changes in auditory function – auditory nerve brainstem evoked responses (ABR) and distortion product otoacoustic emissions (DPOAEs) – were evaluated in each of these animals and compared with those in rats exposed to noise only and in control groups of rats. Statistical evaluation of the results showed that when assessed with ABR, each of the heat-acclimated, noise-exposed groups was protected from the noise, even the group that was heat-acclimated after the noise exposure. When assessed with DPOAE, protection was statistically apparent only in the group that was heat acclimated, then exposed to noise, and not in the other groups. Thus, heat acclimation provides protection against permanent noise-induced hearing loss.
Effect of the Long-Term Treatment with Trandolapril on Endoglin Expression in Rats with Experimental Renal Fibrosis Induced by Renal Mass Reduction
Authors: Prieto Marta , Rodríguez-Peña Ana , Arévalo Miguel , Rivas Juan V. , Düwel Annette , Eleno Nélida , Sánchez Rafael J. , Morales Ana I. , López-Novoa José M. , Pérez-Barriocanal Fernando
Published: October 2004

Background: Endoglin is a membrane glycoprotein that regulates TGF-β1 signaling. Previous studies have revealed that endoglin is upregulated in several models of experimental fibrosis, and that endoglin expression can counteract the fibrogenic effects of TGF-β1. As treatment with angiotensin converting enzyme (ACE) inhibitors reduces renal fibrosis by mechanisms that are, in part, not dependent on angiotensin II blockade, we have assessed the hypothesis that this effect could be mediated by endoglin upregulation. Methods: We have used the 5/6-nephrectomy renal mass reduction (RMR) model of renal fibrosis in rats treated (RMR+T) or not treated with the ACE inhibitor trandolapril (0.7 mg/kg/day). One, 3 and 5 months after RMR, mean arterial pressure and renal function were measured. In addition, renal fibrosis was evaluated quantitatively and endoglin, TGF-β1, collagen type I and collagen type IV expression was assessed by Northern blot and immunohistochemistry. Results: RMR induced a progressive increase in mean arterial pressure, urinary protein excretion and glomerular and tubulointerstitial fibrosis, which is accompanied by an increased expression of TGF-β1, endoglin and collagen types I and IV. Trandolapril treatment reduced systemic blood pressure and lessened proteinuria after RMR, as well as expression of TGF-β1, endoglin and collagens. Conclusion: The present study demonstrates an increased TGF-β1, endoglin, collagen type I and collagen type IV expression in rats with severe hypertension and renal damage. The effect of trandolapril to decrease renal fibrosis seems to be based in a reduced TGF-β1 expression but not in an increased expression of endoglin.
Training Counseling Psychologists as Social Justice Agents
Authors: Goodman Lisa A. , Liang Belle , Helms Janet E. , Latta Rachel E. , Sparks Elizabeth , Weintraub Sarah R.
Published: October 2004

Despite recent calls for counseling psychology to embrace social justice-oriented work, there has been little discussion about what such work actually looks like. The first part of this article derives a set of principles from feminist and multicultural counseling theories that counseling psychologists should consider as they engage in social justice work. These include (a) ongoing self-examination,(b) sharing power, (c) giving voice, (d) facilitating consciousness raising, (e) building on strengths, and(f) leaving clients the tools to work toward social change. The second part of the article describes a program designed to integrate social justice work into the core curriculum of the Boston College doctoral program. The authors discuss ways in which the above principles have shaped students; activities, and some of the ethical dilemmas that have emerged. Finally, the article under-scores professional obstacles that counseling psychologists doing social justice work are likely to face, and offers recommendations for overcoming them.
Psychological Hedonism, Evolutionary Biology, and the Experience Machine
Authors: Lemos John
Published: October 2004

In the second half of their recent, critically acclaimed book Unto Others: The Evolution and Psychology of Unselfish Behavior, Elliott Sober and David Sloan Wilson discuss psychological hedonism. This is the view that avoiding our own pain and increasing our own pleasure are the only ultimate motives people have. They argue that none of the traditional philosophical arguments against this view are good, and they go on to present theirownevolutionary biological argument against it. Interestingly, the first half of their book, which is a defense of group selectionism, has received almost all of the attention of those people who have published reactions to the book. No one has published a detailed reaction to the argument of the latter half of the book. In this article, the author explains and critically discusses their evolutionary biological argument against psychological hedonism, concluding that in its current form it is not strong enough to support its conclusion. However, the author goes on to argue that despite recent criticisms of Robert Nozick’s experience-machine argument, it is still a good argument against psychological hedonism. In support of the latter point, the author responds to the objections of Sober and Wilson and to the more recent criticisms offered by Matthew Silverstein.
Passive versus Active Parental Permission in School-Based Survey Research
Authors: Eaton Danice K. , Lowry Richard , Brener Nancy D. , Grunbaum Jo Anne , Kann Laura
Published: October 2004

This study investigates whether the type of parental permission affects prevalence estimates for risk behaviors from the national 2001 Youth Risk Behavior Survey. Participants were 13,195 students from 143 schools, of which 65% used passive permission and 35% active permission. Student participation rates were 86.7% in passive permission schools and 77.3% in active permission schools. For 24 of 26 behaviors tested, no significant differences were seen in the prevalence of risk behavior by type of parental permission. As long as high response rates are obtained, type of parental permission does not affect prevalence estimates for risk behaviors that are based on self-report.
The Effect of Action Orientation on the Academic Performance of Undergraduate Marketing Majors
Authors: Jaramillo Fernando , Spector Paul E.
Published: October 2004

Due to the effect of academic performance on employment opportunities and admission to graduate schools, researchers have long recognized the need for identifying factors that are linked to the academic performance of undergraduate marketing students. This research proposes a model that investigates the relationships among motivation, effort, personality, stress, and academic performance. Action-state orientation (AO-SO) is an important factor in students’ emotional exhaustion and effort. AO-SO relates to individual differences in the capacity to regulate emotions, cognitions, and behaviors to accomplish intentional actions. AO-SO consists of three dimensions: disengagement (versus preoccupation), volatility (versus persistency), and hesitation (versus initiative). Results indicate that persistency and initiative are positively related to effort, which is an important antecedent of academic performance. Also, disengagement is negatively related to emotional exhaustion.
Can Public Management Reform Be Allied With Staff Participation?
Authors: Leisink Peter
Published: October 2004

Plans for management reform are subject to mandatory consultation with staff representatives. Indirect staff participation is generally viewed as a complement of direct forms of participation. The case of one public bus company offers an opportunity to examine the effects of teamwork on service performance and quality of work and the contribution of staff participation to the reform process. The effects of teamwork are positive, and teams are interested in enhancing public service. However, the contribution of indirect staff participation to the reform process is faced with suspicion of infringement of employment rights and employee solidarity.
Human Resource Management and Job Satisfaction in the Dutch Public Sector
Authors: Steijn Bram
Published: October 2004

Academic research on public administration devotes relatively little attention to issues concerning human resource management (HRM) and job satisfaction. Many private sector studies suggest that investing in HRM has positive effects on worker morale. Therefore, in this study, variables measuring HRM practices were combined with an analysis of determinants of job satisfaction in the Dutch public sector. Three hypotheses were tested and confirmed. They revealed that (a) individual characteristics have a negligible effect on job satisfaction, (b) HRM practices have a positive effect, but (c) this latter effect is largely indirect and mediated by job and organizational characteristics.
Adolescent Personality
Authors: Baker Spencer R. , Victor James B. , Chambers Anthony L. , Halverson Charles F.
Published: October 2004

The purpose of this study was to investigate convergent and discriminant validity of the five-factor model of adolescent personality in a school setting using three different raters (methods): self-ratings, peer ratings, and teacher ratings. The authors investigated validity through a multitrait-multimethod matrix and a confirmatory factor analysis correlated trait, uncorrelated method model. With the exception of Emotional Stability, each analysis demonstrated similar patterns and together provided support for the convergent and discriminant validity of the five-factor model structure of adolescent personality. However, among the three raters, self-ratings of personality provided a comparatively weaker method for assessing adolescent personality. The influences of agreement between self and other raters are discussed in relation to contrast, perceiver, and target effects; expert observer effects; the degree of acquaintanceship; and the effect of the social context.
The Relationship Between Classroom Motivation and Academic Achievement in Elementary‐School‐Aged Children
Authors: Broussard Sheri Coates , Garrison M. E. Betsy
Published: October 2004

The relationship between motivation and academic success has been better established with older children and adults than with younger children. As part of a larger project, the purpose of this study was to examine the relation‐ship between classroom motivation and academic achievement in young elementary‐school‐aged children. The participants were 122 first‐grade and 129 third‐grade children from a mid‐sized city in the southern United States. The findings from the current study were consistent with previous research in that higher levels of mastery motivation and judgment motivation were found to be related to higher math and reading grades in third graders. However, higher levels of mastery motivation, not judgment motivation, were related to higher math and reading grades in first graders.
Low dose pramipexole is neuroprotective in the MPTP mouse model of Parkinson's disease, and downregulates the dopamine transporter via the D3 receptor
Authors: Joyce Jeffrey N , Woolsey Cheryl , Ryoo Han , Borwege Sabine , Hagner Diane
Published: October 2004

Background

Our aim was to determine if pramipexole, a D3 preferring agonist, effectively reduced dopamine neuron and fiber loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model when given at intraperitoneal doses corresponding to clinical doses. We also determined whether subchronic treatment with pramipexole regulates dopamine transporter function, thereby reducing intracellular transport of the active metabolite of MPTP, 1-methyl-4-phenylpyridinium (MPP+).

Methods

Ten 12-month old C57BL/6 mice were treated with MPTP (or saline) twice per day at 20 mg/kg s.c. (4 injections over 48 h). Mice were pretreated for 3 days and during the 2-day MPTP regimen with pramipexole (0.1 mg/kg/day) or saline. Stereological quantification of dopamine neuron number and optical density measurement of dopamine fiber loss were carried out at 1 week after treatment, using immunostaining for dopamine transporter (DAT) and tyrosine hydroxylase (TH). Additional wild-type (WT) and D3 receptor knockout (KO) mice were treated for 5 days with pramipexole (0.1 mg/kg/day) or vehicle. The kinetics of [3H]MPP+ and [3H]DA uptake (Vmax and Km) were determined 24 h later; and at 24 h and 14 days dopamine transporter density was measured by quantitative autoradiography.

Results

Pramipexole treatment completely antagonized the neurotoxic effects of MPTP, as measured by substantia nigra and ventral tegmental area TH-immunoreactive cell counts. MPTP- induced loss of striatal innervation, as measured by DAT-immunoreactivity, was partially prevented by pramipexole, but not with regard to TH-IR. Pramipexole also reduced DAT- immunoreactivity in non-MPTP treated mice. Subchronic treatment with pramipexole lowered the Vmax for [3H]DA and [3H]MPP+ uptake into striatal synaptosomes of WT mice. Pramipexole treatment lowered Vmax in WT but not D3 KO mice; however, D3 KO mice had lower Vmax for [3H]DA uptake. There was no change in DAT number in WT with pramipexole treatment or D3 KO mice at 24 h post-treatment, but there was a reduction in WT-pramipexole treated and not in D3 KO mice at 14 days post-treatment.

Conclusion

These results suggest that protection occurs at clinically suitable doses of pramipexole. Protection could be due to a reduced amount of MPP+ taken up into DA terminals via DAT. D3 receptor plays an important role in this regulation of transporter uptake and availability.
Significance of MDR1 and multiple drug resistance in refractory human epileptic brain
Authors: Marchi Nicola , Hallene Kerri L , Kight Kelly M , Cucullo Luca , Moddel Gabriel , Bingaman William , Dini Gabriele , Vezzani Annamaria , Janigro Damir
Published: October 2004

Background

The multiple drug resistance protein (MDR1/P-glycoprotein) is overexpressed in glia and blood-brain barrier (BBB) endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs) can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs.

Methods

Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated.

Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker.

Results

MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased.

Conclusions

Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.
A further critique of the analytic strategy of adjusting for covariates to identify biologic mediation
Authors: Kaufman Jay S , MacLehose Richard F , Kaufman Sol
Published: October 2004

Background

Epidemiologic research is often devoted to etiologic investigation, and so techniques that may facilitate mechanistic inferences are attractive. Some of these techniques rely on rigid and/or unrealistic assumptions, making the biologic inferences tenuous. The methodology investigated here is effect decomposition: the contrast between effect measures estimated with and without adjustment for one or more variables hypothesized to lie on the pathway through which the exposure exerts its effect. This contrast is typically used to distinguish the exposure's indirect effect, through the specified intermediate variables, from its direct effect, transmitted via pathways that do not involve the specified intermediates.

Methods

We apply a causal framework based on latent potential response types to describe the limitations inherent in effect decomposition analysis. For simplicity, we assume three measured binary variables with monotonic effects and randomized exposure, and use difference contrasts as measures of causal effect. Previous authors showed that confounding between intermediate and the outcome threatens the validity of the decomposition strategy, even if exposure is randomized. We define exchangeability conditions for absence of confounding of causal effects of exposure and intermediate, and generate two example populations in which the no-confounding conditions are satisfied. In one population we impose an additional prohibition against unit-level interaction (synergism). We evaluate the performance of the decomposition strategy against true values of the causal effects, as defined by the proportions of latent potential response types in the two populations.

Results

We demonstrate that even when there is no confounding, partition of the total effect into direct and indirect effects is not reliably valid. Decomposition is valid only with the additional restriction that the population contain no units in which exposure and intermediate interact to cause the outcome. This restriction implies homogeneity of causal effects across strata of the intermediate.

Conclusions

Reliable effect decomposition requires not only absence of confounding, but also absence of unit-level interaction and use of linear contrasts as measures of causal effect. Epidemiologists should be wary of etiologic inference based on adjusting for intermediates, especially when using ratio effect measures or when absence of interacting potential response types cannot be confidently asserted.
Resistance to IL-10 inhibition of interferon gamma production and expression of suppressor of cytokine signaling 1 in CD4+T cells from patients with rheumatoid arthritis
Authors: Yamana Jiro , Yamamura Masahiro , Okamoto Akira , Aita Tetsushi , Iwahashi Mitsuhiro , Sunahori Katsue , Makino Hirofumi
Published: October 2004

IL-10 has been shown to block the antigen-specific T-cell cytokine response by inhibiting the CD28 signaling pathway. We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased. The phosphorylation of signal transducer and activator of transcription 3 was sustained in both blood and synovial tissue CD4+ T cells of RA, but it was not augmented by the presence of 1 ng/ml IL-10. Sera from RA patients induced signal transducer and activator of transcription 3 phosphorylation in normal CD4+ T cells, which was mostly abolished by neutralizing anti-IL-6 antibody. Preincubation of normal CD4+ T cells with IL-6 reduced IL-10-mediated inhibition of interferon gamma production. Blood CD4+ T cells from RA patients contained higher levels of suppressor of cytokine signaling 1 but lower levels of suppressor of cytokine signaling 3 mRNA compared with control CD4+ T cells, as determined by real-time PCR. These results indicate that RA CD4+ T cells become resistant to the immunosuppressive effect of IL-10 before migration into synovial tissue, and this impaired IL-10 signaling may be associated with sustained signal transducer and activator of transcription 3 activation and suppressor of cytokine signaling 1 induction.
Lower Incidence of Colorectal Cancer and Later Age of Disease Onset in 27 Families With Pathogenic MSH6 Germline Mutations Compared With Families With MLH1 or MSH2 Mutations: The German Hereditary Nonpolyposis Colorectal Cancer Consortium
Authors: Plaschke Jens , Engel Christoph , Krüger Stefan , Holinski-Feder Elke , Pagenstecher Constanze , Mangold Elisabeth , Moeslein Gabriela , Schulmann Karsten , Gebert Johannes , von Knebel Doeberitz Magnus , Rüschoff Josef , Loeffler Markus , Schackert Hans K.
Published: October 2004

Purpose

The aim of the study was the analysis of the involvement and phenotypic manifestations of MSH6 germline mutations in families suspected of hereditary nonpolyposis colorectal cancer (HNPCC).

Patients and Methods

Patients were preselected among 706 families by microsatellite instability, immunohistochemistry, and/or exclusion of MLH1 or MSH2 mutations and were subjected to MSH6 mutation analysis. Clinical and molecular data of MSH6 mutation families were compared with data from families with MLH1 and MSH2 mutations.

Results

We identified 27 families with 24 different pathogenic MSH6 germline mutations, representing 3.8% of the total of the families, and 14.7% of all families with DNA mismatch repair (MMR) gene mutations (n = 183). The median age of onset of colorectal cancer in putative mutation carriers was 10 years higher for MSH6 (54 years; 95% CI, 51 to 56) compared with MLH1 and MSH2 (44 years; 95% CI, 43 to 45; log-rank test, P = .0038). Relative to other malignant tumors, colorectal cancer was less frequent in MSH6 families compared with MLH1 and MSH2 families (Fisher's exact test, P < .001). In contrast, the frequency of non–HNPCC-associated tumors was increased (Fisher's exact test, P < .001).

Conclusion

Later age of disease onset and lower incidence of colorectal cancer may contribute to a lower proportion of identified MSH6 mutations in families suspected of HNPCC. However, in approximately half of these families, at least one patient developed colorectal or endometrial cancer in the fourth decade of life. Therefore, a surveillance program as stringent as that for families with MLH1 or MSH2 mutations is recommended.
Giant Infiltrative Cavernous Malformation: Clinical Presentation, Intervention, and Genetic Analysis: Case Report
Authors: Lawton Michael T. , Vates G Edward , Quiñones-Hinojosa Alfredo , McDonald William C. , Marchuk Douglas A. , Young William L.
Published: October 2004

OBJECTIVE AND IMPORTANCE:

Cavernous malformations can present in children with a sporadic course of repeated hemorrhage and enlargement, but they are rarely aggressive, infiltrative, or multilobar. We present the case of a young boy with a complex cavernous malformation that evolved during the course of a decade to encompass the majority of his right cerebral hemisphere.

CLINICAL PRESENTATION:

A 16-month-old boy presented with seizures, and radiographic studies demonstrated a large cavernous malformation in his right frontal pole. During the next 10 years, his seizures became intractable, and he developed progressive left hand weakness and atrophy. His malformation infiltrated his entire right frontal lobe as well as portions of his right parietal lobe, temporal lobe, and deep gray matter structures.

INTERVENTION:

The patient underwent right hemicraniotomy and near total resection of the lesion. Pathological analysis revealed dilated, thin-walled vessels separated by small amounts of intervening astrogliotic brain consistent with cavernous malformation. The patient recovered to his baseline neurological condition and has had no seizure or hemorrhage since his operation. Genetic testing did not reveal mutations in either the CCM1 (KRIT1) or CCM2 (malcavernin) genes.

CONCLUSION:

This case may represent an atypical variant of cavernous malformation best termed giant infiltrative cavernous malformation. Despite its unusual size, multilobar location, and aggressive infiltration, it can be managed effectively with standard surgical resection.
Intraparenchymal Myxopapillary Ependymoma: Case Report
Authors: Tzerakis Nikolaos , Georgakoulias Nikolaos , Kontogeorgos George , Mitsos Aristotelis , Jenkins Alistair , Orphanidis George
Published: October 2004

OBJECTIVE AND IMPORTANCE:

Myxopapillary ependymoma is a histological variant of ependymoma found in the cauda equina region. The most characteristic histological feature of myxopapillary tumors is the abundance of intercellular and perivascular mucin and the arborizing vasculature, which tends to form papillae. Primary intracerebral myxopapillary ependymomas are extremely rare; only three cases have been reported in the previous literature.

CLINICAL PRESENTATION:

A 68-year-old man presented with disorientation and dizziness caused by a cystic left frontal intraparenchymal lesion. This proved to be a myxopapillary ependymoma. Similarities to previously reported cases are discussed, as are the findings on magnetic resonance imaging. There is also a literature review of the histological findings, natural history, and outcome of surgically treated myxopapillary ependymoma.

INTERVENTION:

The lesion was totally removed. After surgery, the patient was neurologically intact and had an uneventful recovery.

CONCLUSION:

This is the fourth reported case of histologically proven primary myxopapillary intracranial ependymoma.
Aneurysmal Bone Cyst of the Atlas: Successful Treatment through Selective Arterial Embolization: Case Report
Authors: Mohit A Alex , Eskridge Joseph , Ellenbogen Richard , Shaffrey Christopher I.
Published: October 2004

OBJECTIVE AND IMPORTANCE:

Aneurysmal bone cysts (ABCs) are benign and expansile osteolytic lesions that can occur in any location in the spine, including the craniovertebral junction. Aggressive resection followed by bone grafting has been the mainstay of treatment, with selective arterial embolization as a presurgical adjunct. Complete excision of these lesions at the craniovertebral junction is associated with high surgical morbidity. We report a case of successful treatment of an ABC of the atlas in a child with selective arterial embolization alone.

CLINICAL PRESENTATION:

A 10-year-old girl presented with persistent neck pain after a snowboarding accident. Computed tomography and magnetic resonance imaging of the cervical spine revealed an expansile cystic mass involving the right lateral mass of C1. Digital subtraction angiography revealed a tumor blush, which, along with the cystic appearance of the lesion, was consistent with an ABC.

INTERVENTION:

The arterial feeders to the lesion were selectively embolized with polyvinyl alcohol particles. Three sessions of embolization were required to eradicate the blood supply to the lesion completely.

CONCLUSION:

Complete surgical resection of ABCs at the craniovertebral junction can be associated with high morbidity secondary to the highly vascular and destructive nature of these lesions. The case discussed here demonstrates the viability of selective arterial embolization as a primary and stand-alone modality of treatment.
Spinal Arachnoid Cyst Containing Nevus Cells in a Patient with a Large Congenital Melanocytic Nevus: Case Report
Authors: Morioka Motohiro , Hamada Jun-ichiro , Ohmori Yuki , Kageshita Toshiro , Ushio Yukitaka
Published: October 2004

OBJECTIVE AND IMPORTANCE:

Spinal arachnoid cysts are rare, and their cause and pathogenesis remain controversial. We experienced a rare case with a large congenital melanocytic nevus in which a spinal arachnoid cyst contained nevus cells, suggesting the congenital nature of a spinal arachnoid cyst.

CLINICAL PRESENTATION:

A 37-year-old Japanese man had been born with a large melanocytic nevus on his back. He experienced intermittent pain radiating to both thighs and to the lower back and waist. A magnetic resonance imaging study disclosed the presence of a posterior intradural extramedullary arachnoid cyst extending from T10 through T12. His spinal cord was displaced anteriorly and flattened.

INTERVENTION:

An osteoplastic laminoplasty was performed, and the arachnoid cyst was totally removed. The cyst membrane exhibited many foci of brown deposits, and histological examination disclosed the presence of melanin-containing cells in the cyst membrane. Morphologically and immunohistochemically, the melanin-containing cells in the cyst membrane were similar to nevus cells in the dermis.

CONCLUSION:

The histological findings of our case suggest that the patient's spinal arachnoid cyst was formed at the same stage of development as the melanocytic nevus.
Multiple Successful Revisions of a Ventriculoureteral Shunt without Nephrectomy for the Treatment of Hydrocephalus: Case Report
Authors: Ohaegbulam Chima , Peters Craig , Goumnerova Liliana
Published: October 2004

OBJECTIVE:

Ventriculoureteral shunts have been described occasionally for patients with complicated hydrocephalus. Repeated successful revision of the distal end of such a shunt has not been reported previously. We report a case in which this was achieved.

CLINICAL PRESENTATION:

A 21-year-old woman with long-standing hydrocephalus, numerous prior shunt revisions and failures, and several distal shunt sites was shunted successfully into her right ureter.

INTERVENTION:

On two occasions, proximal shunt infections required shunt externalization, and the distal end was reinserted successfully into the same distal ureter both times. The patient recovered well from surgery with no clinical evidence of shunt malfunction.

CONCLUSION:

Multiple distal target failures are an unusual but difficult problem in patients with hydrocephalus. Ventriculoureteral shunts without nephrectomy should be considered, and they can be reused successfully if necessary.
Transient Magnetic Resonance Imaging Signal Alterations in the Brainstem after Microvascular Decompression for Trigeminal Neuralgia: Case Report
Authors: Ali M Jafer , Gebarski Stephen , Thompson B Gregory
Published: October 2004

OBJECTIVE AND IMPORTANCE:

We present a case of transient signal alterations along the brainstem path of the trigeminal nerve after microvascular decompression in a patient with trigeminal neuralgia. Such signal changes have been previously reported to represent infarction, but in our patient, they seemed to represent reactive neural and nuclear changes attributable to operative manipulation.

CLINICAL PRESENTATION:

A 43-year-old woman presented with gradually increasing, medically refractory recurrent trigeminal neuralgia 16 months after initial successful microvascular decompression for trigeminal neuralgia. Repeat microvascular decompression resulted initially in complete pain relief; however, her pain suddenly returned on the 3rd postoperative day. Magnetic resonance imaging (MRI) of this recurrent pain revealed new signal alterations along the brainstem path of the trigeminal nerve. Other than marked reduction in her trigeminal neuralgia, the patient had no postoperative alterations of trigeminal sensory or motor function.

INTERVENTION:

The patient's residual postoperative trigeminal neuralgia was successfully treated with carbamazepine. Because of the absence of worrisome signs and symptoms corresponding to the MRI signal alterations, no additional therapy was elected. Follow-up MRI in 1 month revealed near-complete resolution of the postoperative signal alterations along the brainstem path of the trigeminal nerve.

CONCLUSION:

MRI signal alterations along the brainstem path of the trigeminal nerve after microvascular decompression may be only reactive and do not always represent infarction. Depending on the clinical picture, observation may be all that is necessary in such cases.
Resolution of Intracranial Hypertension after Elevation of Depressed Cranial Fracture over the Superior Sagittal Sinus:Case Report
Authors: Binder Devin K. , Sarkissian Vahé , Schmidt Meic H. , Pitts Lawrence H.
Published: October 2004

OBJECTIVE AND IMPORTANCE:

It is common neurosurgical wisdom that depressed cranial fractures (DCFs) over the superior sagittal sinus (SSS) should not be elevated because of the risk of fatal venous hemorrhage.

CLINICAL PRESENTATION:

A 34-year-old man presented with severe headache and diplopia after a motor vehicle accident. Clinical examination demonstrated severe papilledema and bilateral abducens palsy. Imaging findings demonstrated a DCF over the posterior third of the SSS and absent flow distal to the fracture with dilated cortical venous drainage.

INTERVENTION:

Conservative treatment with acetazolamide only partially alleviated the patient's headache and diplopia. Definitive surgical treatment via elevation of the DCF was discussed and decided upon. Twelve days after injury, the patient underwent midline parieto-occipital craniotomy with successful elevation of the DCF off the posterior third of the SSS. Postoperative magnetic resonance venograms revealed restoration of patency in the SSS with reduced tortuosity of cortical veins. The patient's headache resolved, and his papilledema and diplopia resolved gradually.

CONCLUSION:

Elevation of DCF over the SSS can be attempted in cases in which favorable bone anatomy and the patient's clinical condition warrant. This may result in rapid and dramatic resolution of signs and symptoms of secondary intracranial hypertension.