bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Recapitulation of Central Nervous System Development by Murine Embryonic Stem Cell-Derived Neural Stem/Progenitor Cells
Authors: Okada Yohei , Matsumoto Arifumi , Shimazaki Takuya , Enoki Ryosuke , Koizumi Amane , Ishii Seiji , Itoyama Yasuto , Sobue Gen , Okano Hideyuki
Published: August 2008

Neural stem/progenitor cells (NS/PCs) can generate a wide variety of neural cells. However, their fates are generally restricted, depending on the time and location of NS/PC origin. Here we demonstrate that we can recapitulate the spatiotemporal regulation of central nervous system (CNS) development in vitro by using a neurosphere-based culture system of embryonic stem (ES) cell-derived NS/PCs. This ES cell-derived neurosphere system enables the efficient derivation of highly neurogenic fibroblast growth factor-responsive NS/PCs with early temporal identities and high cell-fate plasticity. Over repeated passages, these NS/PCs exhibit temporal progression, becoming epidermal growth factor-responsive gliogenic NS/PCs with late temporal identities; this change is accompanied by an alteration in the epigenetic status of the glial fibrillary acidic protein promoter, similar to that observed in the developing brain. Moreover, the rostrocaudal and dorsoventral spatial identities of the NS/PCs can be successfully regulated by sequential administration of several morphogens. These NS/PCs can differentiate into early-born projection neurons, including cholinergic, catecholaminergic, serotonergic, and motor neurons, that exhibit action potentials in vitro. Finally, these NS/PCs differentiate into neurons that form synaptic contacts with host neurons after their transplantation into wild-type and disease model animals. Thus, this culture system can be used to obtain specific neurons from ES cells, is a simple and powerful tool for investigating the underlying mechanisms of CNS development, and is applicable to regenerative treatment for neurological disorders.

Disclosure of potential conflicts of interest is found at the end of this article.
The Cycle of the Seminiferous Epithelium in Humans: A Need to Revisit?
Authors: Amann Rupert P.
Published: September 2008

ABSTRACT: Understanding the dynamics of spermatogenesis is central to clinical andrology or to probing environmental effects on human testes. This review considers what is known about renewal and proliferation of spermatogonia, how germ cells are organized in cellular associations constituting the cycle of the seminiferous epithelium, relative frequencies of cellular associations, durations of the cycle of the seminiferous epithelium and spermatogenesis, and measurement of daily sperm production. Daily sperm production (DSP) per testis tends to decline with advancing age. Regardless of age, there is substantial loss of potential sperm from degeneration of spermatocytes, but not spermatids. DSP per gram testis parenchyma or DSP per testis cannot be predicted on the basis of testis size or age of a man. The review shows why our 1960s data base is neither robust nor precise and suggests how deficiencies might be rectified. New cellular associations should be defined, with none representing >15% of the cycle of the seminiferous epithelium. Then determine when Apale‐spermatogonia become committed to proliferate or how many mitotic divisions occur thereafter. Restudy the duration of spermatogenesis because the accepted value might be in error by ∼6 days. Restudying human spermatogenesis will benefit clinicians, toxicologists, and epidemiologists probing testis function by direct evaluations or indirectly via evaluations of quantity and quality of sperm ejaculated. It also will benefit scientists interested in renewal and proliferation of spermatogonia, or a spermatogonium as a prototype stem cell.
Endocrine Disruptors, Genital Development, and Hypospadias
Authors: Wang Ming‐Hsien , Baskin Laurence S.
Published: September 2008

ABSTRACT: Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 125 live male births. Embryological studies have demonstrated that, depending on where the urethral development arrests, the meatal opening can be anywhere along the shaft of the penis or, in more severe forms, within the scrotum or in the perineum. Currently, the only available treatment is surgery. If left uncorrected, especially in its severe form, there is risk of infertility and psychological effects, such as avoidance of intimate relationships. The cause of hypospadias is largely unknown; however, current epidemiology and laboratory studies have shed new light into the etiology of hypospadias. With recent advancements in molecular biology and microarray technology, it appears that hypospadias is potentially related to disrupted gene expression. Specifically, some of the environmental chemicals are acting as antiandrogens and interfere directly with the action of testosterone‐related gene expression. In this paper, we briefly review the normal development of male external genitalia and the prevalence and environmental risk factors related to hypospadias. In addition, we discuss some of the recent laboratory findings that contribute to our current understanding of this disease.
The Effect of 5 α‐Reductase Inhibitors on Erectile Function
Authors: Canguven Onder , Burnett Arthur L.
Published: September 2008

ABSTRACT:The 5 α‐reductase inhibitors, which inhibit conversion of testosterone to dihydrotestosterone, are used for miscellaneous clinical applications, including the treatment of benign prostatic hyperplasia and male pattern hair loss, and for possible reduction of the risk of prostate cancer. Erectile dysfunction has been associated with 5 α‐reductase inhibitors. Overall, reports in the literature suggest rates of erectile dysfunction to be between 0.8%–33% in men using these medications. However, randomized controlled studies report the rates of erectile dysfunction to be between 0.8%–15.8%. The possible risk association is that these medications impact androgen function, which is understood to contribute to normal erectile physiology. The 5 α‐reductase inhibitors result in a drop in median serum dihydrotestosterone levels by 60%–93% within 2 years, but there is no major change in testosterone levels. In this review, we surveyed studies on erectile dysfunction in patients treated with 5 α‐reductase inhibitors and critically examined the evidence that associates 5 α‐reductase inhibitors and erectile dysfunction. We conclude that 5 α‐reductase inhibitors do not lead to erectile dysfunction to a significant degree, and we support the position that dihydrotestosterone is less relevant than testosterone in erectile function.
The DNA/RNA‐Binding Protein, Translin, Binds microRNA122a and Increases Its In Vivo Stability
Authors: Yu Zuoren , Hecht Norman B.
Published: September 2008

ABSTRACT: Translin (TSN), also known as testis‐brain RNA‐binding protein, is proposed to bind to breakpoint junctions at chromosomal translocations in the nucleus and to specific RNAs in the cytoplasm. In germ cells of the mouse testis, it recognizes target mRNAs transcribed by the transcription factor CREM‐tau in spermatids, specific meiotically expressed mRNAs, and a noncoding RNA that encodes piRNAs. Here we show that TSN also binds to the microRNA miR‐122a. MiR‐122a is expressed in late‐stage germ cells and is complementary to a sequence in the 3′ untranslated region of the transition protein 2 mRNA. The binding of TSN to miR‐122a increases its in vivo stability, suggesting an additional posttranscriptional function for TSN.
Comparison of two-dimensional and three-dimensional systems for kinematic analysis of the sagittal motion of canine hind limbs during walking
Authors: Kim Jongmin , Rietdyk Shirley , Breur Gert J.
Published: September 2008

Objective—To test the hypotheses that kinematic data of the sagittal motion of canine hind limbs during walking obtained with a 2-dimensional (2-D) system correlate well with those obtained with a 3-dimensional (3-D) system and that the data obtained with the 2-D system are repeatable.

Animals—6 adult dogs with no evidence of lameness.

Procedures—Hind limb motions of 6 walking dogs were recorded via 2-D video and 3-D optoelectric systems simultaneously. Five valid trials were digitized, and 5 data sets (2-D 60 Hz, 3-D 180 Hz, 3-D sagittal 180 Hz, 3-D 60 Hz, and 3-D sagittal 60 Hz) of a complete gait cycle were created for each dog. In sagittal data sets, 3-D data were reduced to exclude coordinates for mediolateral orientation. Temporospatial parameters; angles of hip, stifle, and tarsal joints; and coefficients of variation of angular measurements of each dog were calculated for each data set. Accuracy of the 2-D analysis was determined by calculating mean absolute differences and estimating agreement between the 2-D and 3-D 180-Hz data sets.

Results—Values of joint angles and angular excursions measured with the 2-D system were repeatable and agreed with respective values obtained with the 3-D system. Reduction of the sampling rate had a greater impact on values of kinematic variables obtained with the 3-D system than did elimination of data on mediolateral orientation.

Conclusions and Clinical Relevance—Kinematic analysis using a 2-D video system provided accurate and repeatable data of the sagittal angular motion of canine hind limbs during walking.
Use of high-frequency ultrasonography for evaluation of skin thickness in relation to hydration status and fluid distribution at various cutaneous sites in dogs
Authors: Diana Alessia , Guglielmini Carlo , Fracassi Federico , Pietra Marco , Balletti Erika , Cipone Mario
Published: September 2008

Objective—To assess the usefulness of high-frequency diagnostic ultrasonography for evaluation of changes of skin thickness in relation to hydration status and fluid distribution at various cutaneous sites in dogs.

Animals—10 clinically normal adult dogs (6 males and 4 females) of various breeds.

Procedures—Ultrasonographic examination of the skin was performed before and after hydration via IV administration of an isotonic crystalloid solution (30 mL/kg/h for 30 minutes). A 13-MHz linear-array transducer was used to obtain series of ultrasonographic images at 4 different cutaneous sites (the frontal, sacral, flank, and metatarsal regions). Weight and various clinicopathologic variables (PCV; serum osmolality; and serum total protein, albumin, and sodium concentrations) were determined before and after the infusion. These variables and ultrasonographic measurements of skin thickness before and after hydration were compared.

Results—Among the 10 dogs, mean preinfusion skin thickness ranged from 2,211 μm (metatarsal region) to 3,249 μm (sacral region). Compared with preinfusion values, weight was significantly increased, whereas PCV; serum osmolality; and serum total protein, albumin, and sodium concentrations were significantly decreased after infusion. After infusion, dermal echogenicity decreased and skin thickness increased significantly by 21%, 14%, 15%, and 13% in the frontal, sacral, flank, and metatarsal regions, respectively.

Conclusions and Clinical Relevance—Cutaneous site and hydration were correlated with cutaneous characteristics and skin thickness determined by use of high-frequency ultrasonography in dogs. Thus, diagnostic ultrasonography may be a useful tool for the noninvasive evaluation of skin hydration in healthy dogs and in dogs with skin edema.
Evaluation of the effect of ranitidine on gastroduodenal contractile activity and gastric emptying in horses
Authors: Maher Omar , Nieto Jorge E. , Stanley Scott D. , Dore Elizabeth , Snyder Jack R.
Published: September 2008

Objective—To determine the effect of ranitidine on gastric emptying in horses.

Animals—11 adult horses.

Procedures—In vitro, isolated muscle strips from the pyloric antrum and duodenum of 5 horses were suspended in baths and attached to isometric force transducers. Once stable spontaneous contractions were observed, ranitidine or diluent was added at cumulative increasing concentrations. Isometric stress responses were compared. In vivo, 6 horses were assigned to a group in a prospective randomized crossover study design with a wash-out period of 2 weeks between trials. Ranitidine (2.2 mg/kg) or saline (0.9% NaCl) solution was administered IV, and 15 minutes later, acetaminophen (20 mg/kg), diluted in 400 mL of water, was administered via nasogastric tube to evaluate the liquid phase of gastric emptying. Serum acetaminophen concentration was measured at several time points for 3 hours by use of liquid chromatography tandem mass spectrometry. Frequency of defecation was recorded during the 3 hours of the study.

Results—Ranitidine increased the contractile activity of the pyloric antrum smooth muscle at a concentration of 10−4 M. No significant effect of ranitidine on plasma kinetics of acetaminophen was identified. Frequency of defecation did not differ between groups.

Conclusions and Clinical Relevance—Ranitidine did increase gastric motility in vitro, but no effect on liquid phase gastric emptying was identified in healthy horses by use of the acetaminophen absorption model. Results do not support the use of ranitidine to promote gastric emptying.
Effects of topical application of taurolidine on second intention healing of experimentally induced wounds in rats
Authors: Simpson Jennifer M. , Séguin Bernard , Gitelman Alix I.
Published: September 2008

Objective—To determine the macroscopic effects of topical application of taurolidine on second intention healing of experimentally induced wounds in rats.

Animals—32 adult Sprague-Dawley female rats.

Procedures—In each rat, 2 skin wounds were created in the lumbar area. Groups of 7 rats were assigned to have 1 wound treated topically with hydroxycellulose gel (HDCG), 2% taurolidine in HDCG (T-HDCG), 2% taurolidine–sodium citrate solution, or bacitracin-neomycin-polymyxin B ointment; the other wound was not treated. Four control rats (8 untreated wounds) were used. Wounds were monitored for contraction, epithelialization, and complete healing at 4, 8, and 14 days after wound creation. The number of days to complete healing was also recorded for each wound.

Results—Compared with other treatments or untreated wounds, wounds treated with T-HDCG had decreased total healing at day 8 and decreased epithelialization and decreased total healing at day 14. Wounds treated with T-HDCG required approximately 3 days longer to completely heal than all other treated and untreated wounds. Application of bacitracinneomycin-polymyxin B ointment did not enhance wound healing. Mean time to complete healing of untreated wounds in all treatment and control groups was 10.00 to 10.14 days.

Conclusions and Clinical Relevance—In rats, topical application of T-HDCG to wounds had a negative effect on second intention healing by delaying the epithelialization process. In mammals, generally, wounds treated topically with taurolidine may need to be treated and monitored for a longer period than other wounds treated with other common woundhealing compounds or untreated wounds.
Diagnosis and treatment of dynamic closed-mouth jaw locking in a dog
Authors: Frazho Jean K. , Tano Cheryl A. , Ferrell Eric A.
Published: September 2008

Case Description—A 5-year-old neutered male English Bulldog was evaluated for intermittent closed-mouth jaw locking of approximately 1 week's duration.

Clinical Findings—Initial physical examination revealed a nonpainful inability to open the jaw with and without manual assistance; however, manipulation of the jaw after the dog was sedated for diagnostic imaging restored jaw function. Anesthesia was subsequently induced, and computed tomography was performed with the jaw open and closed; contrast agent–enhanced images of the closed jaw were also obtained. No abnormalities of the temporomandibular joints or retrobulbar space were detected. Fluoroscopic examination of movement of the temporomandibular joints revealed a dynamic interference of the rostrodorsal aspect of the coronoid process of the left mandibular ramus with the medial surface of the frontal process of the left zygomatic bone or the left orbital ligament.

Treatment and Outcome—Partial excision of the coronoid process of the left mandibular ramus was performed. The dog recovered without complication and was able to open and close its jaw and eat within 6 hours after surgery. No additional episodes of jaw locking were detected during the 6 months after surgery.

Clinical Relevance—To the authors' knowledge, closed-mouth jaw locking in animals attributable to dynamic interference of the rostrodorsal aspect of the coronoid process of a mandibular ramus with the medial surface of the frontal process of a zygomatic bone or an orbital ligament has not been described. Surgical excision of the coronoid process of the mandibular ramus appeared to provide a successful outcome in the dog of this report.
Thrombi in the trachea of a dog secondary to placement of a tracheotomy tube
Authors: Fitzwater Kathryn L. , Marks Steven L. , Hanel Rita M.
Published: September 2008

Case Description—A 7-year-old Spaniel-crossbreed dog was evaluated for stertorous breathing and inspiratory stridor.

Clinical Findings—A temporary tracheotomy tube was placed prior to referral. Results of physical examination at our facility, including thoracic auscultation, were unremarkable. Examination of the larynx revealed a 2 × 2-cm nodular mass on the lateral aspect of the epiglottis and left arytenoid cartilage. Cytologic examination of the mass indicated septic suppurative inflammation and intracellular rod-shaped bacteria. During the procedures, decreased air movement through the temporary tracheotomy tube was detected, and the tube was replaced. A thrombus was found on the distal end of the temporary tracheotomy tube; the thrombus obstructed 90% of the tube lumen. Approximately 12 hours later, auscultation revealed decreased sounds in all lung fields. Cervical and thoracic radiography revealed an intraluminal soft tissue opacity distal to the tracheotomy tube. A thrombus that contained hair and plant material was removed from the trachea by use of an embolectomy catheter and videogastroscope. Approximately 30 hours after removal of the initial thrombus, the dog had an episode of respiratory distress. Cervical radiography revealed another intraluminal opacity. It was another thrombus, which also was removed by use of the videogastroscope.

Treatment and Outcome—Tracheoscopy was performed with a videogastroscope in an attempt to remove the thrombi. A Fogarty catheter was used to remove the initial intraluminal thrombus from the trachea.

Clinical Relevance—Airway obstruction resulting from an intraluminal thrombus in the trachea should be considered as a secondary complication after tracheotomy tube placement.
Comparison of four methods to assess colostral IgG concentration in dairy cows
Authors: Chigerwe Munashe , Tyler Jeff W. , Middleton John R. , Spain James N. , Dill Jeffrey S. , Steevens Barry J.
Published: September 2008

Objective—To determine sensitivity and specificity of 4 methods to assess colostral IgG concentration in dairy cows and determine the optimal cutpoint for each method.

Design—Cross-sectional study.

Animals—160 Holstein dairy cows.

Procedures—171 composite colostrum samples collected within 2 hours after parturition were used in the study. Test methods used to estimate colostral IgG concentration consisted of weight of the first milking, 2 hydrometers, and an electronic refractometer. Results of the test methods were compared with colostral IgG concentration determined by means of radial immunodiffusion. For each method, sensitivity and specificity for detecting colostral IgG concentration < 50 g/L were calculated across a range of potential cutpoints, and the optimal cutpoint for each test was selected to maximize sensitivity and specificity.

Results—At the optimal cutpoint for each method, sensitivity for weight of the first milking (0.42) was significantly lower than sensitivity for each of the other 3 methods (hydrometer 1, 0.75; hydrometer 2, 0.76; refractometer, 0.75), but no significant differences were identified among the other 3 methods with regard to sensitivity. Specificities at the optimal cutpoint were similar for all 4 methods.

Conclusions and Clinical Relevance—Results suggested that use of either hydrometer or the electronic refractometer was an acceptable method of screening colostrum for low IgG concentration; however, the manufacturer-defined scale for both hydrometers overestimated colostral IgG concentration. Use of weight of the first milking as a screening test to identify bovine colostrum with inadequate IgG concentration could not be justified because of the low sensitivity.
Understanding university reform in Japan through the prism of the social sciences
Authors: Goodman Rogers
Published: September 2008

This article looks at current university reforms in Japan through two slightly different social science prisms: how social science methodologies and theories can help us understand those reforms better and how social science teaching in universities will be affected by the current reform processes.
'Internationalisation' and the Social Sciences
Authors: Mills David
Published: September 2008

We hear ever more about the internationalisation of higher education. As U.K. universities become increasingly exposed to the vagaries of international student demand, administrators are scrambling to develop ‘internationalisation’ strategies, whilst academics are being encouraged to incorporate ‘international perspectives’ into their curricula. Even the U.K.’s Centre for Learning and Teaching Sociology, Anthropology and Politics (C-SAP) has a strategic aim to promote ‘best practice in the internationalisation of the student learning experience’. It sounds impressive, but what does it mean in practice? Internationalisation has become a buzzword that everyone can use without having to agree on what they mean. The word’s descriptive malleability is its analytical downfall.
Knowledge, society, higher education and the society of control
Authors: Høstaker Roar , Vabø Agnete
Published: September 2008

Research and higher education are, to a greater extent, being governed and evaluated by other than fellow scholars. These changes are discussed in relation to Gilles Deleuze's notion of a transition from 'societies of discipline' to what he called 'societies of control'. This involves a shift from pyramidshaped organisations, built upon authority, to a set of lateral controls and hybrid power structures. This theory and its logic are compared with other theories that have been used to explain such changes in higher education: New Public Management, new modes of knowledge production, academic capitalism, trust and the role of higher education in social reproduction. The development of lateral controls is analysed in relation to the de-coupling of the state as the guarantor of academic quality, the changing status of the academic disciplines and scientific employees, managerialism, the new modularised study programmes and the changing position of external stakeholders. The article, drawing on empirical studies from higher education in Norway, suggests possible affects of the change to 'societies of control' on research, teaching and learning in higher education.
A prospective blinded evaluation of deep brain stimulation for the treatment of secondary dystonia and primary torticollis syndromes
Authors: Pretto Theresa E. , Dalvi Arif , Kang Un Jung , Penn Richard D.
Published: August 2008

Object

The aim of this study was to provide an objective assessment of deep brain stimulation (DBS) for groups of patients with mixed secondary dystonia and primary torticollis syndromes by a blinded evaluation of 13 consecutive patients who underwent ineffective medical treatment and botulinum toxin injections.

Methods

Nine patients with secondary dystonia and 4 with cranial dystonia involving prominent spasmodic torticollis were selected for a DBS implant after they underwent unsuccessful medical treatment. Preoperative videos and neurological assessments were obtained and the DBS implant was inserted into the globus pallidus internus. Postoperatively, DBS parameters were adjusted to provide optimal benefit. Postoperative videotapes and quality of life scores were obtained. Blinded randomized evaluation of videotapes was performed by a neurologist specializing in movement disorders. Videos were scored using the Unified Dystonia Rating Scale, Toronto Western Spasmodic Torticollis Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale, or Abnormal Involuntary Movement Scale. Quality of life scoring was assessed using a standardized 7-point Global Rating Scale.

Results

All 13 patients completed preoperative videotaping, medical assessment, and surgery. Optimal DBS programming was completed in 6.5 visits over 5.9 months. Seven patients reported marked improvement, 3 reported moderate improvement, 2 reported slight improvement or no change, and 1 was lost to follow-up. Examiner scores on the Global Rating Scale reflected patient self-reported scores.

Conclusions

Global subjective gains and notable objective improvement were observed in 11 of 13 patients. Although the benefits were variable and not fully predictable, they were of sufficient magnitude to justify offering the procedure when medications and botulinum toxin injections have failed.
Intraventricular occurrence of a melanocytoma
Authors: Tandon Nitin , O'Neill Thomas J , Vollmer Dennis G. , Wang Min
Published: August 2008

Melanocytomas are rare tumors of the central nervous system that are believed to arise from leptomeningeal melanocytes. A young girl presented with a contrast-enhancing cystic mass in the temporal horn of the left lateral ventricle. Microsurgical resection of a black-colored vascular tumor supplied by the anterior choroidal artery was performed. Appropriate immunohistochemical staining and electron microscope evaluations were used to confirm the pathological diagnosis. The patient made an excellent recovery; follow-up imaging revealed no recurrent or residual tumor. This is the first documented primary occurrence of a melanocytoma in an intraventricular location. The intraventricular occurrence of this tumor suggests that melanocytes may migrate into the choroidal fissure and may infrequently undergo neoplastic proliferation in that location. This case contains implications for the differential diagnosis of intraventricular tumors.
Effects of erythropoietin on reducing brain damage and improving functional outcome after traumatic brain injury in mice
Authors: Xiong Ye , Lu Dunyue , Qu Changsheng , Goussev Anton , Schallert Timothy , Mahmood Asim , Chopp Michael
Published: August 2008

Object

This study was designed to investigate the beneficial effects of recombinant human erythropoietin (rhEPO) treatment of traumatic brain injury (TBI) in mice.

Methods

Adult male C57BL/6 mice were divided into 3 groups: 1) the saline group (TBI and saline [13 mice]); 2) EPO group (TBI and rhEPO [12]); and 3) sham group (sham and rhEPO [8]). Traumatic brain injury was induced by controlled cortical impact. Bromodeoxyuridine (100 mg/kg) was injected daily for 10 days, starting 1 day after injury, for labeling proliferating cells. Recombinant human erythropoietin was administered intraperitoneally at 6 hours and at 3 and 7 days post-TBI (5000 U/kg body weight, total dosage 15,000 U/kg). Neurological function was assessed using the Morris water maze and footfault tests. Animals were killed 35 days after injury, and brain sections were stained for immunohistochemical evaluation.

Results

Traumatic brain injury caused tissue loss in the cortex and cell loss in the dentate gyrus (DG) as well as impairment of sensorimotor function (footfault testing) and spatial learning (Morris water maze). Traumatic brain injury alone stimulated cell proliferation and angiogenesis. Compared with saline treatment, rhEPO significantly reduced lesion volume in the cortex and cell loss in the DG after TBI and substantially improved recovery of sensorimotor function and spatial learning performance. It enhanced neurogenesis in the injured cortex and the DG.

Conclusions

Recombinant human erythropoietin initiated 6 hours post-TBI provided neuroprotection by decreasing lesion volume and cell loss as well as neurorestoration by enhancing neurogenesis, subsequently improving sensorimotor and spatial learning function. It is a promising neuroprotective and neurorestorative agent for TBI and warrants further investigation.
Endoscopic anatomy of the fourth ventricle
Authors: Longatti Pierluigi , Fiorindi Alessandro , Feletti Alberto , D'Avella Domenico , Martinuzzi Andrea
Published: August 2008

Object

Microsurgical anatomy of the fourth ventricle has been comprehensively addressed by masterly reports providing classic descriptions of this complex region. Neuroendoscopy could offer a new, somewhat different perspective of the “inside” view of the fourth ventricle. The purpose of this study was to examine from the anatomical point of view the access to the fourth ventricle achieved by the endoscopic transaqueductal approach, to enumerate and describe the anatomically identifiable landmarks, and to compare them with those described during microsurgery.

Methods

The video recordings of 52 of 75 endoscopic explorations of the fourth ventricle performed at the authors' institution for different pathological conditions were reviewed and evaluated to identify and describe every anatomical landmark. According to the microsurgical anatomy, at least 23 superficial structures are clearly identifiable in the fourth ventricle, and they represent the comparative basis of parallel endoscopic anatomy of the structures found during the fourth ventricle navigation.

Results

The following anatomical structures were identified in all cases: median sulcus, superior and inferior vela medullare, choroid plexus, inferior fovea, hypoglossal and vagal triangles, area postrema, obex, canalis medullaris, lateral recess, and the foramina of Luschka and Magendie. The median eminence, facial colliculus, striae medullaris, auditory tubercle, and inferior fovea were seen in the majority of cases. The locus caevruleus could never be seen.

Conclusions

On the whole, 20 anatomical structures could consistently be identified by exploring the fourth ventricle with a fiberscope. Neuroendoscopy offers a quite different outlook on the anatomy of the fourth ventricle, and compared with the microsurgical descriptions it seems to provide a superior and detailed visualization, particularly of the structures located in the inferior triangle.
Magnetic resonance imaging for quantitative flow measurement in infants with hydrocephalus: a prospective study
Authors: Leliefeld Paul H. , Gooskens Rob H. J. M. , Vincken Koen L. , Ramos Lino M. P. , van der Grond Jeroen , Tulleken Cees A. F. , Kappelle L. Jaap , Hanlo Patrick W.
Published: August 2008

Object

Raised intracranial pressure (ICP) that is associated with hydrocephalus may lead to alterations in cerebral hemodynamics and ischemic changes in the brain. In infants with hydrocephalus, defining the right moment for surgical intervention based on clinical signs alone can sometimes be a difficult task. Clinical signs of raised ICP are known to be unreliable and sometimes even misleading. Furthermore, when sutures are closed, ICP does not always correlate with the size of the ventricles or with the clinical signs or symptoms. In this study the authors investigated whether cerebral blood flow (CBF) can be measured by using quantitative MR angiography in infants with progressive hydrocephalus. In addition, the authors investigated the relationship between CBF and ICP, before and after cerebrospinal fluid (CSF) diversion.

Methods

Fifteen infants with progressive hydrocephalus (age range 1 day–7 months) were examined. All patients underwent anterior fontanel pressure measurement, MR angiography, and mean arterial blood pressure measurements before and after CSF diversion. Brain volume was measured to compensate for the physiological increase in CBF during brain maturation in infants.

Results

The mean preoperative ICP was 19.1 ± 8.4 cm H2O (± standard deviation). The mean postoperative ICP was 6.7 ± 4.0 cm H2O (p < 0.005). The mean preoperative CBF was 25.7 ± 11.3 ml/100 cm3 brain/min. After CSF diversion, CBF increased to 50.1 ± 12.1 ml/100 cm3 brain/min (p < 0.005). The mean arterial blood pressure did not change after surgical intervention.

Conclusions

Magnetic resonance imaging can be used to measure CBF in infants with hydrocephalus. Raised ICP was related to a decrease in CBF. After CSF diversion, CBF and ICP improved to values within the normal range.
Two-year-old girl with cervicomedullary junction stenosis and an unknown type of skeletal dysplasia
Authors: Cheshier Samuel Henry , Kalani Mohammad Yashar Sorena , Pendakaur Arjun , Higgins Dominique , Kahn David , Shendel Stephen , Shuer Lawrence
Published: August 2008

The authors present a novel case of skeletal dysplasia in a 2.8-year-old girl. The patient presented with progressive lower cranial nerve palsy and myelopathy due to constriction at the cervicomedullary junction caused by overgrowth of the occipital bone of the foramen magnum and the C-1. She also had prominent bone overgrowth of the superior orbital ridges, resulting in excessive stretching of periorbital skin and an inability to fully close her eyes.
Rapid progression of hypothyroidism-related pituitary hyperplasia
Authors: Lee Ching-Yi , Hsu Hsun-Hun , Lai Hung-Yi , Lee Shih-Tseng
Published: August 2008

Sellar and suprasellar masses are related to many factors. The authors report on a 10.3-year-old female patient who presented with growth retardation. Initial normal results of a hormone study and rapid progression of hypothyroidism-related pituitary hyperplasia within a 4-week interval were noted. The mass disappeared after thyroxine treatment. The authors conclude that repeated hormone examinations and avoidance of an unnecessary operation are needed in such patients.
Magnetic field interactions in adjustable hydrocephalus shunts
Authors: Lavinio Andrea , Harding Sally , Van Der Boogaard Floor , Czosnyka Marek , Smielewski Peter , Richards Hugh K. , Pickard John D. , Czosnyka Zofia H.
Published: August 2008

Object

Exposing patients with ventricular shunts to magnetic fields and MR imaging procedures poses a significant risk of unintentional changes in shunt settings. Shunt valves can also generate considerable imaging artifacts. The purpose of this study was to determine the magnetic field safety and MR imaging compatibility of 5 adjustable models of hydrocephalus shunts.

Methods

The Codman Hakim (regular and with SiphonGuard), Miethke ProGAV, Medtronic Strata, Sophysa Sophy and Polaris programmable valves were tested in a low-intensity magnetic field, and then translational attraction (TA), magnetic torque (MT), and volume of artifacts on T1-weighted spin echo (SE) and gradient echo (GE) pulse sequences in a 3-T MR imaging unit were measured.

Results

The ProGAV and Polaris valves were immune to unintentional reprogramming by magnetic fields up to 3 T. Other valves randomly changed settings, starting from the intensity of field: Sophy valve 24 mT, Strata valve 30 mT, and both Codman Hakim programmable valves from 42 mT. Shunt performances in the 3-T MR imaging unit are reported in the order of compatibility: 1) Codman Hakim regular, TA = 0.005 N, MT = 0.000 Nm, GE = 30 cm3, SE = 2 cm3; 2) Miethke ProGAV, TA = 0.001 N, MT = 1.4 × 10−3 Nm, GE = 231 cm3, SE = 13 cm3; 3) Codman Hakim with SiphonGuard, TA = 0.005 N, MT = 2.3 × 10−3 Nm, GE = 233 cm3, SE = 19 cm3; 4) Medtronic Strata, TA = 0.27 N, MT = 18.0 × 10−3 Nm, GE = 484 cm3, SE = 86 cm3; 5) Sophysa Sophy, TA = 0.82 N, MT = 38.9 × 10−3 Nm, GE = 758 cm3, SE = 72 cm3; and 6) Sophysa Polaris, TA = 0.80 N, MT = 39.6 × 10−3 Nm, GE = 954 cm3, SE = 100 cm3.

Conclusions

All valves, with the exception of the Polaris and ProGAV models, are prone to unintentional reprogramming when exposed to heterogeneous magnetic fields stronger than 40 mT. All tested valves can be considered safe for 3-T MR imaging. All valves generated a distortion of the MR image, especially the GE sequences.
Senkenanrechnung gemäss Kyoto-Protokoll: Perspektiven für die Waldwirtschaft | Taking carbon sinks into account according to the Kyoto Protocol: a prospect for the forest sector
Authors: Volz Richard
Published: September 2008

The Kyoto Protocol makes provisions for carbon sinks from forest management to be taken into account as a contribution towards fulfilling a country's emission reduction target. Additional emission allowances are allocated for these forest carbon sinks. If Switzerland uses this extra contingent of allowances to the full it would then only have to reduce emissions by 4.5% instead of the actual target of 8%. Emission allowances from carbon sinks can be traded on the emissions trading market and be claimed by forest owners. An assessment of the income that could be anticipated was carried out in four forestry companies: with the CO2 price set at 10 CHF per ton it was seen that a potential revenue of between 6 and 71 CHF per hectare and year could be realised. However, the legal basis for allocating emission allowances from carbon sinks to forest owners has yet to be created. In view of the fact that the two chambers of Parliament refused the introduction of the Forests Act Revision Bill, it is not clear if and in what form this will be done. For the period after 2012, the rules will be renegotiated at the international level and it is expected that the carbon stored in harvested wood products will be taken into account. Accordingly, wood removed from the forest would no longer be automatically counted as a CO2 source in the emission balance.
The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon‐α activity and low tumor necrosis factor α levels in patients with lupus
Authors: Kariuki Silvia N. , Crow Mary K. , Niewold Timothy B.
Published: August 2008

Objective

The C1858T polymorphism in PTPN22 has been associated with the risk of systemic lupus erythematosus (SLE) as well as multiple other autoimmune diseases. We have previously shown that high serum interferon‐α (IFNα) activity is a heritable risk factor for SLE. The aim of this study was to determine whether the PTPN22 risk variant may shift serum cytokine profiles to higher IFNα activity, resulting in risk of disease.

Methods

IFNα was measured in 143 patients with SLE, using a functional reporter cell assay, and tumor necrosis factor α (TNFα) was measured by enzyme‐linked immunosorbent assay. The rs2476601 single‐nucleotide polymorphism in PTPN22 (C1858T) was genotyped in the same patients. Patients were grouped, using a clustering algorithm, into 4 cytokine groups (IFNα predominant, IFNα and TNFα correlated, TNFα predominant, and both IFNα and TNFα low).

Results

SLE patients carrying the risk allele of PTPN22 had higher serum IFNα activity than patients lacking the risk allele (P = 0.027). TNFα levels were lower in carriers of the risk allele (P = 0.030), and the risk allele was more common in patients in the IFNα‐predominant and IFNα and TNFα‐correlated groups as compared with patients in the TNFα‐predominant and both IFNα and TNFα‐low groups (P = 0.001). Twenty‐five percent of male patients carried the risk allele, compared with 10% of female patients (P = 0.024); however, cytokine skewing was similar in both sexes.

Conclusion

The autoimmune disease risk allele of PTPN22 is associated with skewing of serum cytokine profiles toward higher IFNα activity and lower TNFα levels in vivo in patients with SLE. This serum cytokine pattern may be relevant in other autoimmune diseases associated with the PTPN22 risk allele.
Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis
Authors: Hamada Takashi , Torikai Motofumi , Kuwazuru Ai , Tanaka Motoyuki , Horai Naoto , Fukuda Takeshi , Yamada Shingo , Nagayama Shinichi , Hashiguchi Kanehisa , Sunahara Nobuhiko , Fukuzaki Koichiro , Nagata Ryoichi , Komiya Setsuro , Maruyama Ikuro , Fukuda Takeo , Abeyama Kazuhiro
Published: August 2008

Objective

Tissue hypoxia is closely associated with arthritis pathogenesis, and extracellular high mobility group box chromosomal protein 1 (HMGB‐1) released from injured cells also has a role in arthritis development. This study was thus undertaken to investigate the hypothesis that extracellular HMGB‐1 may be a coupling factor between hypoxia and inflammation in arthritis.

Methods

Concentrations of tumor necrosis factor α, interleukin‐6, vascular endothelial growth factor, lactic acid, lactate dehydrogenase, and HMGB‐1 were measured in synovial fluid (SF) samples from patients with inflammatory arthropathy (rheumatoid arthritis and pseudogout) and patients with noninflammatory arthropathy (osteoarthritis). The localization of tissue hypoxia and HMGB‐1 was also examined in animal models of collagen‐induced arthritis (CIA). In cell‐based experiments, the effects of hypoxia on HMGB‐1 release and its associated cellular events (i.e., protein distribution and cell viability) were studied.

Results

In SF samples from patients with HMGB‐1–associated inflammatory arthropathy (i.e., samples with HMGB‐1 levels >2 SD above the mean level in samples from patients with noninflammatory arthropathy), concentrations of HMGB‐1 were significantly correlated with those of lactic acid, a marker of tissue hypoxia. In CIA models in which the pathologic phenotype could be attenuated by HMGB‐1 neutralization, colocalization of HMGB‐1 with tissue hypoxia in arthritis lesions was also observed. In cell‐based experiments, hypoxia induced significantly increased levels of extracellular HMGB‐1 by the cellular processes of secretion and/or apoptosis‐associated release, which was much more prominent than the protein release in necrotic cell injury potentiated by oxidative stress.

Conclusion

These findings indicate that tissue hypoxia and its resultant extracellular HMGB‐1 might play an important role in the development of arthritis.
Repression of chondrogenesis through binding of notch signaling proteins HES‐1 and HEY‐1 to N‐box domains in the COL2A1 enhancer site
Authors: Grogan Shawn P. , Olee Tsaiwei , Hiraoka Koji , Lotz Martin K.
Published: August 2008

Objective

Notch signaling is implicated in the repression of mesenchymal stem cell (MSC) chondrogenic differentiation. The purpose of this study was to examine the mechanism of this repression and how it is modulated to permit chondrogenesis.

Methods

Notch intracellular domain (NICD) protein levels were monitored via Western blotting throughout chondrogenic differentiation of human MSCs in pellet cultures. Overexpression of Notch signaling components and their effect on chondrogenesis was achieved by transfecting plasmids coding for NICD, HES‐1, and HERP‐2/HEY‐1. COL2A1 and AGGRECAN expression was monitored via quantitative polymerase chain reaction analysis. Chromatin immunoprecipitation (ChIP) was used to test whether HES‐1 and HEY‐1 bind putative N‐box domains in intron 1 of COL2A1.

Results

High levels of NICD proteins were reduced during chondrogenesis of human MSCs, and this was mediated by transforming growth factor β3 (TGFβ3). COL2A1 gene expression was repressed following overexpression of NICD (2‐fold) and HES‐1 (3‐fold) and was markedly repressed by overexpression of HEY‐1 (80‐fold). HEY‐1 repressed AGGRECAN expression 10‐fold, while NICD and HES‐1 had no effect. We identified 2 putative N‐box domains adjacent to, and part of, the SOX9 enhancer binding site located in intron 1 of COL2A1. ChIP studies showed that endogenous HES‐1 and HEY‐1 bound to these sites. Transducin‐like enhancer, the HES‐1 corepressor protein, was displaced during chondrogenic differentiation and following TGFβ3 treatment.

Conclusion

These results reveal novel mechanisms by which Notch signaling represses gene expression. Notch signaling proteins act on the SOX9 binding site in the COL2A1 enhancer and prevent SOX9‐mediated transcriptional activation of COL2A1 and, thus, chondrogenic differentiation.
Ocrelizumab, a humanized anti‐CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I/II randomized, blinded, placebo‐controlled, dose‐ranging study
Authors: Genovese Mark C. , Kaine Jeffrey L. , Lowenstein Mitchell B. , Giudice José Del , Baldassare Andrew , Schechtman Joy , Fudman Edward , Kohen Michael , Gujrathi Sheila , Trapp Robert G. , Sweiss Nadera J. , Spaniolo Greg , Dummer Wolfgang ,   ACTION Study Group
Published: August 2008

Objective

Ocrelizumab, a humanized anti‐CD20 monoclonal antibody, was studied in a first‐in‐human trial in rheumatoid arthritis (RA) patients receiving concomitant methotrexate (MTX).

Methods

The ACTION trial was a combined phase I/II study of placebo plus MTX versus ocrelizumab plus MTX in 237 RA patients (intent‐to‐treat population). During phase I, 45 patients were treated with 1 of 5 escalating doses of study drug (infusions on days 1 and 15, 10–1,000 mg per each infusion). An additional 192 patients were randomized during phase II. Eligible patients had active disease, an inadequate response to treatment with at least MTX, rheumatoid factor positivity, and elevated levels of acute‐phase reactants. The total study duration was 72 weeks. B cell pharmacodynamics over time was investigated.

Results

Baseline demographics were similar among the treatment groups. Based on the entire 72‐week data set, the incidence of serious adverse events in the ocrelizumab‐treated patients was 17.9%, as compared with 14.6% in placebo‐treated patients. The incidence of serious infections was 2.0% in all ocrelizumab‐treated patients and 4.9% in placebo‐treated patients. Infusion‐associated adverse events were mostly grade 1 or grade 2 and were more frequent around the time of the first infusion. No serious infusion‐associated adverse events were reported in the ocrelizumab group. Evidence of clinical activity was observed at all doses evaluated. Peripheral B cell depletion after infusion was rapid at all doses, with earlier repletion of B cells at doses of 10 mg and 50 mg. Human anti‐human antibodies were detected in 19% and 10%, respectively, of those receiving 10 mg and 50 mg of ocrelizumab, compared with 0–5% of those receiving 200, 500, and 1,000 mg.

Conclusion

Ocrelizumab therapy in combination with MTX was well tolerated. Doses of 200 mg (2 infusions) and higher showed better clinical responses, better reduction of C‐reactive protein levels, and very low immunogenicity.