bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural Representations of Temporally Modulated Signals in the Auditory Thalamus of Awake Primates
Authors: Bartlett Edward L. , Wang Xiaoqin
Published: October 2006

In sensory systems, the thalamus has historically been considered a relay station. Neural representations of temporal modulations in the auditory system undergo considerable changes as they pass from the inferior colliculus (IC) to the auditory cortex. We sought to determine in awake primates the extent to which auditory thalamic neurons contribute to these transformations. We tested the temporal processing capabilities of medial geniculate body (MGB) neurons in awake marmoset monkeys using repetitive click stimuli. MGB neurons were able to synchronize to periodic clicks at repetition rates significantly higher than auditory cortex neurons. Unlike responses in the MGB of anesthetized animals, >40% of MGB neurons in awake marmosets displayed nonsynchronized discharges when stimulated by high click rates (short interclick intervals). Such nonsynchronized MGB responses typically occurred at higher repetition rates than those observed in auditory cortex. In contrast to auditory cortex neurons, many MGB neurons exhibited both synchronized and nonsynchronized discharge patterns. In both MGB and auditory cortex, synchronized and nonsynchronized responses represented complementary ranges of interclick intervals (1/click rate). Furthermore, the temporal processing abilities of some MGB neurons were sensitive to the spectrotemporal parameters of the click stimuli used. Together, these findings suggest that MGB neurons participate in active transformations of the neural representations of temporal modulations from IC to auditory cortex. In particular, the MGB appears to be the first station in the auditory ascending pathway in which substantial nonsynchronized responses emerge.
Pre- and Postsynaptic Activation of M-Channels By a Novel Opener Dampens Neuronal Firing and Transmitter Release
Authors: Peretz Asher , Sheinin Anton , Yue Cuiyong , Degani-Katzav Nurit , Gibor Gilad , Nachman Rachel , Gopin Anna , Tam Eyal , Shabat Doron , Yaari Yoel , Attali Bernard
Published: October 2006

The M-type K+current (M-current), encoded by Kv7.2/3 (KCNQ2/3) K+channels, plays a critical role in regulating neuronal excitability because it counteracts subthreshold depolarizations. Here we have characterized the functions of pre- and postsynaptic M-channels using a novel Kv7.2/3 channel opener, NH6, which we synthesized as a new derivative of N-phenylanthranilic acid. NH6 exhibits a good selectivity as it does not affect Kv7.1 and IKSK+currents as well as NR1/NR2B, AMPA, and GABAAreceptor-mediated currents. Superfusion of NH6 increased recombinant Kv7.2/3 current amplitude (EC50= 18 μM) by causing a hyperpolarizing shift of the voltage activation curve and by markedly slowing the deactivation kinetics. Activation of native M-currents by NH6 robustly reduced the number of evoked and spontaneous action potentials in cultured cortical, hippocampal and dorsal root ganglion neurons. In hippocampal slices, NH6 decreased somatically evoked spike afterdepolarization of CA1 pyramidal neurons and induced regular firing in bursting neurons. Activation of M-channels by NH6, potently reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents. Activation of M-channels also decreased the frequency of miniature excitatory (mEPSC) and inhibitory (mIPSC) postsynaptic currents without affecting their amplitude and waveform, thus suggesting that M-channels presynaptically inhibit glutamate and GABA release. Our results suggest a role of presynaptic M-channels in the release of glutamate and GABA. They also indicate that M-channels act pre- and postsynaptically to dampen neuronal excitability.
Ca2+Flux and Signaling Implications by Nicotinic Acetylcholine Receptors in Rat Medial Habenula
Authors: Guo Xiaochuan , Lester Robin A. J.
Published: October 2006

The fraction of inward current carried by Ca2+( FCa2+) through nicotinic acetylcholine receptors (nAChRs) on acutely isolated rat medial habenula (MHb) neurons was calculated from experiments that simultaneously monitored agonist-induced membrane currents and intracellular [Ca2+], measured with patch-clamp and indo-1 fluorescence, respectively. In physiological concentrations of extracellular Ca2+(2 mM) at −50 mV, the percentage of current carried by Ca2+was determined to be roughly 3–4%, which is in close agreement with measurements from other heteromeric nicotinic receptors expressed in peripheral tissue. Among factors that may have affected this measurement, such as Ca2+influx through voltage-gated Ca2+channels, the concentration of intracellular Ca2+buffer, and Ca2+sequestration and release from intracellular stores, only Ca2+uptake by mitochondria was shown to confound the analysis. Furthermore, we find that because of the high density of nAChRs on MHb cells, low concentrations of ACh (10 μM) and its hydrolysis product, choline (1 mM), can significantly elevate intracellular Ca2+. Moreover, during persistent activation of nAChRs, the level of intracellular Ca2+is proportional to its extracellular concentration in the physiological range. Together, these findings support the suggestion that nAChRs may be capable of sensing low concentrations of diffusely released neurotransmitter and, in addition, transfer information about ongoing local synaptic activity by changes in extracellular Ca2+.
Feedforward Inhibition Controls the Spread of Granule Cell–Induced Purkinje Cell Activity in the Cerebellar Cortex
Authors: Santamaria Fidel , Tripp Patrick G. , Bower James M.
Published: October 2006

Synapses associated with the parallel fiber (pf) axons of cerebellar granule cells constitute the largest excitatory input onto Purkinje cells (PCs). Although most theories of cerebellar function assume these synapses produce an excitatory sequential “beamlike” activation of PCs, numerous physiological studies have failed to find such beams. Using a computer model of the cerebellar cortex we predicted that the lack of PCs beams is explained by the concomitant pf activation of feedforward molecular layer inhibition. This prediction was tested, in vivo, by recording PCs sharing a common set of pfs before and after pharmacologically blocking inhibitory inputs. As predicted by the model, pf-induced beams of excitatory PC responses were seen only when inhibition was blocked. Blocking inhibition did not have a significant effect in the excitability of the cerebellar cortex. We conclude that pfs work in concert with feedforward cortical inhibition to regulate the excitability of the PC dendrite without directly influencing PC spiking output. This conclusion requires a significant reassessment of classical interpretations of the functional organization of the cerebellar cortex.
Lemuriform Origins as Viewed from the Fossil Record
Authors: Godinot Marc
Published: October 2006

Fossils relevant to lemuriform origins are reviewed. Omanodon seems very close to the other early tooth-combed lemuriforms Karanisia, Wadilemur and Saharagalago, whereas Bugtilemur is rejected from the Lemuriformes. The Djebelemurinae, including Djebelemur and ‘Anchomomys’ milleri, are considered as stem lemuriforms preceding tooth comb differentiation; they are shown to be very distinct from European adapiforms. With tooth-combed lemuriforms present in Africa around 40 million years ago, and stem lemuriforms without tooth combs present on the same continent around 50–48 million years ago, a reasonable scenario can be proposed: tooth comb differentiation and lemuriform dispersal to Madagascar between 52–40 million years ago. The possible significance of Plesiopithecus for daubentoniid origins is raised. A critique of molecular dates is presented in the light of the fossil record. Azibiids are possibly early African prosimians. The timing of the dispersal of primates to Africa and the problem of strepsirhine origins are briefly examined.
Lack of Torpor in Free-Ranging Southern Lesser Galagos, Galago moholi: Ecological and Physiological Considerations
Authors: Mzilikazi Nomakwezi , Masters Judith C. , Lovegrove Barry G.
Published: October 2006

Studies investigating heterothermy under natural conditions are particularly scarce for tropical species. However, heterothermy patterns in tropical and subtropical environments often differ markedly from those observed in arctic and temperate species. The investigation of heterothermy in strepsirhine primates has focussed largely on the Malagasy cheirogaleids. In addition, a physiological verification of torpor occurrence in mainland strepsirhines is important with regard to arguments pertaining to the colonization of Madagascar by strepsirhine primates. We measured body temperatures of 11 free-ranging Galago moholi, between February 2002 and September 2003, for 3 consecutive months for each animal. No incidents of heterothermy were recorded throughout the study period. We considered how physiological and ecological aspects of G. moholi biology might have obviated the use of torpor. It was suggested that the breeding pattern observed in G. moholi prevented torpor use whilst increasing fecundity, and that the ecological costs of torpor far outweighed the energetic costs. This study highlights the need for more studies on free-ranging animals to elucidate the physiological, ecological and phylogenetic constraints and determinants of torpor use. Furthermore, if convincing arguments are to be made regarding the possible role of heterothermy in species dispersal, more data from free-ranging animals are needed.
Mid-Term Effectiveness of Behavioral and Psychodynamic Inpatient Treatments of Severe Obesity Based on a Randomized Study
Authors: Beutel M.E. , Dippel A. , Szczepanski M. , Thiede R. , Wiltink J.
Published: October 2006

Background: The objective of this study was to compare the effectiveness of psychodynamic and behavioral inpatient treatments of severely obese patients regarding weight and distress. Methods: In a longitudinal study obese patients (body mass index, BMI ≧35) were randomly assigned to behavioral or to psychodynamic inpatient treatment. Mostly female (n = 267; 85%) obese patients with psychiatric and somatic comorbidity (age 20–64 years, BMI 35–74) were examined with standardized self-report scales on distress (SCL-90R), interpersonal problems (Inventory of Interpersonal Problems), eating behavior (Fragebogen zum Essverhalten) and body image (Fragebogen zum Körperbild). Results: During 49 days (mean) of inpatient treatment, patients lost an average of 5.6 kg (4.4%) in the behavioral (n = 130) and 5.7 kg (4.4%) in the psychodynamic setting (n = 137). In both settings, eating behavior, well-being and body image also improved significantly. One year after discharge, return rate was 73%. Forty percent had further reduced their weight (by more than 5% compared to intake), 36% had regained weight, but were still below intake level, and another 24% had increased weight above intake. Conclusion: Behavioral and psychodynamic treatments were equally effective reducing weight and distress over 1 year.
Recognizing Increased Risk of Depressive Comorbidity after Myocardial Infarction: Looking for 4 Symptoms of Anxiety-Depression
Authors: Denollet Johan , Strik Jacqueline J. , Lousberg Richel , Honig Adriaan
Published: October 2006

Background: Screening for depression in myocardial infarction (MI) patients must be improved: (1) depression often goes unrecognized and (2) anxiety has been largely overlooked as an essential feature of depression in these patients. We therefore examined the co-occurrence of anxiety and depression after MI, and the validity of a brief mixed anxiety-depression index as a simple way to identify post-MI patients at increased risk of comorbid depression. Methods: One month after MI, 176 patients underwent a psychiatric interview and completed the Beck Depression Inventory (BDI) and the Symptoms of Anxiety-Depression index (SAD4) containing four symptoms of anxiety (tension, restlessness) and depression (feeling blue, hopelessness). Results: Thirty-one MI patients (18%) had comorbid depression and 37 (21%) depressive or anxiety disorder. High factor loadings and item-total correlations (SAD4, α = 0.86) confirmed that symptoms of anxiety and depression co-occurred after MI. Mixed anxiety-depression (SAD4≧3) was present in 90% of depressed MI patients and in 100% of severely depressed patients. After adjustment for standard depression symptoms (BDI; OR = 4.4, 95% CI 1.6–12.1, p = 0.004), left ventricular ejection fraction, age and sex, mixed anxiety-depression symptomatology was associated with an increased risk of depressive comorbidity (OR = 11.2, 95% CI 3.0–42.5, p < 0.0001). Mixed anxiety-depression was also independently associated with depressive or anxiety disorder (OR = 9.2, 95% CI 3.0–27.6, p < 0.0001). Conclusions: Anxiety is underrecognized in post-MI patients; however, the present findings suggest that anxiety symptomatology should not be overlooked in these patients. Depressive comorbidity after MI is characterized by symptoms of mixed anxiety-depression, after controlling for standard depression symptoms. The SAD4 represents an easy way to recognize the increased risk of post-MI depression.
Depression Vulnerabilities in Patients with Different Levels of Depressive Symptoms after Acute Coronary Syndromes
Authors: Rieckmann Nina , Burg Matthew M. , Gerin William , Chaplin William F. , Clemow Lynn , Davidson Karina W.
Published: October 2006

Background: Cognitive, behavioral, and interpersonal vulnerabilities have been studied in patients fulfilling diagnostic criteria for major depression and dysthymia. The extent to which these vulnerabilities are present in cardiac patients with mild to moderate depressive symptoms – a risk factor for mortality – is unknown. Moreover, few studies have examined interrelations among depression vulnerabilities. Methods: A consecutive cohort of 314 patients with acute coronary syndrome completed the Beck Depression Inventory (BDI) and measures of cognitive, behavioral, and interpersonal vulnerabilities (Dysfunctional Attitudes Scale, Pleasant Events Schedule for the Elderly, Dyadic Adjustment Scale, and an inventory of role transitions) within 1 week of hospital admission. Of the patients, 166 were classified as nondepressed (BDI score, 0–4), 91 as mildly depressed (BDI score, 10–16), and 57 as moderately to severely depressed (BDI score, >16). Results: Compared with nondepressed patients, both mildly depressed and moderately to severely depressed patients exhibited higher mean levels of all vulnerabilities as well as a higher prevalence of more than one elevated vulnerability, defined by threshold scores. Vulnerabilities were only minimally interrelated (r = 0.01–0.25), and they were independently associated with mild and moderate depressive symptom status. Conclusions: This is the first study to show that cognitive, behavioral, and interpersonal depression vulnerabilities are uniquelyassociated with concurrent depressive symptoms. There appeared to be only modest overlap between vulnerabilities, supporting the idea that depression in medically ill patients is a multifaceted phenomenon, even in the presence of minimally elevated depressive symptoms. Longitudinal studies are required before causality and treatment implications can be addressed.
The Internalising and Externalising Dimensions of Affective Symptoms in Depressed (Unipolar) and Bipolar Patients
Authors: Bech P. , Hansen H.V. , Kessing L.V.
Published: October 2006

Objective: To analyse the internalising and externalising dimensions of affective states in depressed (unipolar) and bipolar patients approximately 2 years after discharge from psychiatric hospitals in Denmark. Method: The 42-item symptom scale based on the Beck Depression Inventory was used for the measurement of both the internalising dimension of affective symptoms (depression including suicidal ideas, anxiety and asthenia) and the externalising dimension (mania). To supplement the latter dimension, the WHO-5 questionnaire was included. These questionnaires were mailed to a large population of patients with depressive (unipolar) or bipolar disorders, representative of patients treated in hospital settings in Denmark, approximately 2 years after discharge from hospital. Results: In total, 244 unipolars and 214 bipolars were included in the study. Mokken analysis showed that depressive (unipolar) patients could be measured more validly than bipolar patients on the internalising subscales of depression, anxiety and asthenia. On the externalising dimension of psychological well-being (WHO-5), both groups of patients could be validly measured. Approximately 2 years after discharge from hospital, around 36% of the unipolars and 19% of the bipolars had a moderate to severe depression. In a control group of healthy subjects, 4% had a moderate to severe depression. Less than 5% even in the bipolar group of patients were hypomanic. Conclusion: Approximately 2 years after discharge from psychiatric hospitals in Denmark, depressive (unipolar) patients scored significantly higher than bipolar patients on the internalising dimension and suicidal ideas, and significantly lower on the externalising dimension of psychological well-being.
The Mental Health of Hospital Workers Dealing with Severe Acute Respiratory Syndrome
Authors: Lu Yi-Ching , Shu Bih-Ching , Chang Yong-Yuan , Lung For-Wey
Published: October 2006

Background: The aim of this study was to explore the impact of the severe acute respiratory syndrome (SARS) on health care workers in Taiwan. The possible predisposing and perpetuating factors in developing mental symptoms were investigated. Methods: Participantsconsisted of 135 health care workers who had had contact with or took care of patients who were probable or suspected SARS cases, during the SARS outbreak, at a teaching hospital in southern Taiwan. All participants completed questionnaires, including the Chinese Health Questionnaire, Eysenck Personality Questionnaire and Parental Bonding Instrument. Results: Twenty-two participants (17.3%) developed significant mental symptoms, and 105 participants (82.7%) showed no obvious symptoms. The structural equation model showed that maternal care (β = –0.18, p = 0.011) and neuroticism (β = 0.54, p < 10–6) directly influenced the ability of health care workers to deal with the impact of SARS. Maternal overprotection (β = 0.30, p < 10–4) had an indirect influence on the ability to cope with the impact of SARS. Conclusion: Both neuroticism and maternal attachment influenced the mental health of health care workers during the SARS epidemic. The results can be a helpful reference for intervention and prevention programs for health care workers facing disasters in the future.
Self-Exposure Treatment of Recurrent Nightmares: Waiting-List-Controlled Trial and 4-Year Follow-Up
Authors: Grandi Silvana , Fabbri Stefania , Panattoni Naike , Gonnella Elisabetta , Marks Isaac
Published: October 2006

Background: In open and randomized controlled trials self-exposure therapy reduced the frequency of nightmares but follow-up ceased at 7 months post-entry. Method: Ten adults who attended an outpatient clinic and had DSM-IV nightmare disorder were put on a 3-month waiting-list. After 3 months they were given a self-exposure manual and were asked to follow its instructions for 4 weeks and were then followed up for 4 years. They were rated at 0, 3, 4, 5, 7, 10, 16, 28 and 52 months. At month 0 only, a matched control group of 10 subjects from the same clinic who had no axis I or II disorder was also rated. Results: At month 0, the nightmare sufferers had more nightmares, anxiety, depression, hostility and somatic symptoms than the matched control group. All 10 nightmare sufferers completed the 3-month waiting-list, 4-week self-exposure therapy and 4-year follow-up without any dropouts. The recurrent nightmares and most associated symptoms did not improve while on the waiting-list but improved markedly after self-exposure therapy and remained improved over the 4-year follow-up. Conclusions: Adults’ recurrent nightmares and associated symptoms failed to improve over a 3-month waiting-list period but reduced greatly after subsequent self-exposure therapy with minimal therapist contact over 1 month, and these gains continued over the next 4 years.
Effects of Insulin-Like Growth Factor I on Transforming Growth Factor β1 Induced Chondrogenesis of Synovium-Derived Mesenchymal Stem Cells Cultured in a Polyglycolic Acid Scaffold
Authors: Sakimura Koichiro , Matsumoto Tomoko , Miyamoto Chikara , Osaki Makoto , Shindo Hiroyuki
Published: October 2006

The aim of this study was to demonstrate the induction of chondrogenesis by transforming growth factor (TGF)-β1 from synovium-derived mesenchymal stem cells in a three-dimensional polyglycolic acid (PGA) scaffold, and to evaluate the effects of insulin-like growth factor (IGF)-I on TGF-β1-induced chondrogenesis. Adult human synovial membranes were obtained from the knees of patients with osteoarthritis or rheumatoid arthritis. Cells were expanded in monolayers, seeded onto a PGA scaffold, and cultured for 4 or 8 weeks in chondrogenic medium containing TGF-β1 with or without IGF-I. As a control, the cells were cultured in chondrogenic medium without TGF-β1. The glycosaminoglycan content was quantified using dimethylmethylene blue dye-binding assay, and the DNA content was measured fluorometrically. Histological examination was also performed using safranin-O staining. The expression of mRNA for aggrecan and collagen type II was confirmed by RT-PCR. After 4 weeks of cultivation with TGF-β1, the cells differentiated to a chondrocytic phenotype, and these chondrogeneses were more potent when cultured for 8 weeks. The combination of IGF-I and TGF-β1 produced higher amounts of glycosaminoglycan than TGF-β1 alone at 8 weeks. In conclusions, chondrogenesis from human synovium-derived mesenchymal cells was identified, and IGF-I plays a role in maintaining the extracellular matrix in combination with TGF-β1.
Treatment of Rabbit Growth Plate Injuries with an Autologous Tissue-Engineered Composite
Authors: Jin Xiao-bing , Luo Zhuo-jing , Wang Jing
Published: October 2006

Tissue engineering has become a promising way of treating growth plate injuries. In this study, we attempted investigating the role of the autologous tissue-engineered composite in the treatment of rabbit growth plate injuries. Growth plate chondrocytes from iliac crest epiphyseal cartilage of immature New Zealand rabbits were obtained by dissection and sequential digestion with 0.2% collagenase (type II). After proliferating in monolayer culture in vitro for 3 weeks, the cells were harvested and seeded onto the demineralized bone matrix (DBM) scaffold to construct the composite. The autologous tissue-engineered composites were finally implanted into the proximal right tibia defects of the growth plate created in 12 rabbits (group A underwent the operation after obtaining chondrocytes 3 weeks beforehand), another 12 rabbits were implanted with only the DBM scaffold (group B), and the defects in group C (12 rabbits) were not implanted. The left tibias of all animals were left undone as the normal control. Two weeks after the operation, severe shortness and angulation deformity of the right tibia evaluated by X-ray were gradually observed in groups B and C. However, there were no obvious changes in group A and there were significant differences between group A and groups B and C (p < 0.05) at the 4-, 8-, and 16-weeks time points. 16 weeks after operation, histological examination revealed that the defects of the right tibias in group A had restored to almost the normal columnar structure of the growth plate. The results demonstrate that tissue-engineered composite established by combination of autologous growth plate chondrocytes and DBM can prevent the formation of a bone bridge and restore the growth of damaged growth plate.
Regulation of α-Smooth Muscle Actin Protein Expression in Adipose-Derived Stem Cells
Authors: Lee Wen-Chi C. , Rubin J. Peter , Marra Kacey G.
Published: October 2006

The objective of this work was to study the response of adipose-derived stem cells (ASCs) to exogenous biochemical stimulation, and the potential of ASCs to differentiate toward the smooth muscle cell (SMC) lineage. Immunofluorescence staining and Western blot analysis detected protein expression of the early SMC marker α-smooth muscle actin (α-SMA) in both control and experiment groups. Expression of α-SMA in ASCs significantly increased when treated with transforming growth factor-β1, while α-SMA expression only slightly increased in the presence of retinoic acid (RA), β-mercaptoethanol and ascorbic acid. Treatment with platelet-derived growth factor-BB, RA and dibutyryl-cyclic adenosine monophosphate decreased the expression of α-SMA significantly. While β-mercaptoethanol and ascorbic acid, as well as RA have resulted in increased α-SMA expression in marrow-derived mesenchymal stem cells and other progenitor cells, our results demonstrate that these treatments do not significantly increase α-SMA expression, indicating that the differentiation potential of ASCs and mesenchymal stem cells may be fundamentally different.
Extracellular Accumulations in the Avian Pituitary Gland: Histochemical Analysis in Two Species of Indian Wild Birds
Authors: Mohanty Banalata
Published: October 2006

Extracellular accumulations of two distinct types, colloid-filled follicles and fibrous-material-containing cysts, were observed in the pituitary gland of two species of Indian wild birds, Halcyon smyrnensis perpulchra and Lonchura striata striata. Colloid follicles were regular structures and distributed throughout the pars distalis (PD). The fibrous cysts were irregular structures, bigger than the colloid follicles and mostly observed towards the ventral margin of the PD. Sometimes disruption of the outer margin with depletion of fibrous material from the cavity was observed. Hormone-secreting cells of various types, anti-adrenocorticotropic-hormone-, anti-prolactin-, anti-growth-hormone- and anti-luteinizing-hormone-immunoreactive cells were encountered bordering both the colloid follicles and fibrous cysts. Neither the colloid nor the fibrous material showed any immunoreaction to any of the pituitary hormone antisera. On histochemical staining colloid was positive to periodic acid-Schiff (PAS) and fibrous materials stained with Alcian blue-PAS-orange G staining. Colloid depositions in the pituitary gland of these two wild birds were correlated to age, more in numbers in the adult birds than in the young ones. Fibrous-material-containing cysts were elucidated in the pituitary gland of adult birds only. These were more prevalent in the pituitary of reproductively active birds. Regular morphology of the colloid follicles, overall distribution in the adenohypophysis and dense nature of deposition of the colloid suggest the accumulation of this type may be the secretory products of both granulated and agranulated pituitary cell types. Absence of immunoreactivity of the colloid against pituitary hormone antisera points out that the storage form may differ chemically from the bioactive hormones. The spatial distribution of fibrous-material-containing cysts mostly towards the ventral PD, observations of immunoreactive cell fragmentations inside the cysts, and their disrupted margins suggest these structures may have some role in discharging the intraglandular degradation products.
Survival Analysis of 81 Children with Primary Spinal Gliomas: A Population-Based Study
Authors: Tseng Jen-Ho , Tseng Ming-Yuan
Published: October 2006

Primary spinal gliomas are rare. Most clinical studies are based on single centers with small numbers of patients and limited length of follow-up. Because data from the Cancer Registry cover larger numbers of patients and longer durations of follow-up, our objective was to define prognostic factors that might predict the survival at a national population level. From 1971 to 1995, data of 81 children (age <15 years) with primary spinal gliomas from the Cancer Registry of England and Wales were analyzed. Median survival and crude survival rates in respect of 7 variables (age, sex, morphology, WHO grade, socioeconomic status, geographical region, and period of diagnosis) were calculated using the Kaplan-Meier method. The Cox regression was performed for estimating hazard ratios (HR) for death. Results showed that the 1-, 5-, and 10-year crude survival rates for this population were 72.84, 60.49, and 58.0%, respectively. Both univariate and multivariate analyses revealed that only morphology (HR 2.79 for nonependymoma, p = 0.05) and WHO grade (HR 6.74 for high grade, p = 0.01) were significant prognostic factors. Results from this population-based study are very helpful for comparison with other population-based studies and for public health purposes.
Intracranial Hemorrhage and Vitamin K Deficiency Associated with Biliary Atresia: Summary of 15 Cases and Review of the Literature
Authors: Akiyama Hideyuki , Okamura Yusuke , Nagashima Tatsuya , Yokoi Akiko , Muraji Toshihiro , Uetani Yoshiyuki
Published: October 2006

Biliary atresia (BA) is a rare disease, characterized by progressive and obliterative cholangiopathy, and is one of the major causes of secondary vitamin K deficiency in infancy. We describe 15 infants (10 female, 5 male) with BA, presenting with intracranial hemorrhage (ICH), including 10 subdural hemorrhages, 4 subarachnoid hemorrhages, 2 intraventricular hemorrhages, and 1 intraparenchymal hemorrhage. The age at onset of ICH ranged from 26 to 79 (mean 54.2) days. Eight patients underwent successful surgical evacuation of ICH, following administration of vitamin K. All 15 patients underwent Kasai portoenterostomy for BA 8–30 days after onset. During a mean follow-up period of 86.8 (range 2–352) months, 4 patients died of liver failure despite lack of neurological sequelae. Two patients underwent living-related donor and 1 patient living-unrelated donor liver transplantation. Only 2 patients suffered neurological signs and symptoms, including mental retardation and epilepsy, whereas 3 were noted to have temporary hemiparesis which recovered completely during the follow-up period. The possibility of BA should be considered in the treatment of ICH due to vitamin K deficiency, since it is reported to be one of the major causes of secondary vitamin K deficiency. Urgent surgical intervention for ICH can be performed successfully following sufficient administration of vitamin K or fresh frozen human plasma. Moreover, early performance of Kasai portoenterostomy is possible even for patients who have undergone craniotomy.
Multiple Intracranial Aneurysms in a Child with Congenital Cyanotic Heart Disease
Authors: Muzumdar D.P. , Sateesh M. , Goel A.
Published: October 2006

A 10-year-old child with transposition of the great arteries had multiple intracranial aneurysms. The child presented with pyogenic meningitis, and the investigations incidentally revealed numerous aneurysms involving both anterior and posterior circulation arteries. Angiography also revealed multiple fistulae between the internal and external carotid arteries. The child is under observation. The pathogenesis and management strategy of multiple intracranial aneurysms are discussed and the relevant literature is briefly reviewed.
Can the Requirement of a Diversion Procedure Be Predicted after an Uncomplicated Intracranial Hydatid Cyst Surgery?
Authors: Önal Çağatay , Erguvan-Önal Rezzan , Yakinci Cengiz , Karayol Ali , Atambay Metin , Daldal Nilgün
Published: October 2006

Intracranial hydatidosis is mainly a pediatric disease. Surgical evacuation of the mass in toto is the gold standard of therapy. No concise data related to the requirement of diversion procedures after uncomplicated hydatid cyst removal is encountered in the literature. The aim of this report is to focus on this idea and estimate the necessity of a diversion procedure beforehand. A 6-year-old girl both with intracranial and renal involvement of hydatidosis underwent surgery. Intact removal of the intracranial cyst harboring daughter vesicles was achieved. A persistent porencephalic cyst at the operative site required a shunt 6 months after surgery. Thick pericyst formation was blamed for this specific progress and the pathophysiology is discussed.
Cerebellar Dermoid Cyst with Occipital Dermal Sinus
Authors: Layadi F. , Louhab N. , Lmejjati M. , Aniba K. , Aït Elqadi A. , Aït Benali S.
Published: October 2006

Intracranial dermoid cyst is a rare entity accounting for 0.1–0.7% of all intracranial tumors. The most common location is in the posterior fossa, at or near the midline. We present 2 pediatric cases with dermal sinus. The first case presented with clinical signs of increased intracranial pressure and cerebellar symptoms. CT scan showed a large and regular midline posterior fossa cyst without contrast enhancement. The second case was revealed by recurrent meningitis. CT scan showed a midline vermis low-density mass with capsular contrast enhancement. Dermal sinus was found in 2 cases. Complete surgical removal was performed followed, in a second operation, by ventriculoperitoneal shunt in 2 cases. There was no postoperative complication in our patients. The aim of this study is to discuss the clinical aspects of dermoid cyst, especially in cases with dermal sinus, and to review the therapeutic strategies in case of associated hydrocephalus.
A Lateral Cervical Lipomyelomeningocele Associated with Diplomyelia
Authors: Shieh Charles , Lam Cornelius H.
Published: October 2006

We report a case of a neonate with complex spinal dysraphism and associated anomalies of the axial skeleton. Based on the clinical presentation and radiographic findings, and recent advances in the understanding of human embryogenesis, we formulate a hypothesis that such a presentation is the result of failure of normal gastrulation. A 1-day-old male neonate presented with multiple right-sided anomalies, including hypoplastic right face and decreased movement of the right upper extremity. Radiographic studies demonstrated absent right cervical hemivertebrae, right cervical lipomyelomeningocele, and cervical diplomyelia with right hemicord terminating in a blind pouch. Anterior and posterior cervical and thoracic fusion with instrumentation was performed at the age of 3 years, and on follow-up the patient had improvement in right upper extremity strength. Complex spinal dysraphism is a pathological process that occurs during different stages in human development. We describe a case involving a rare lateral lipomyelomeningocele in the cervical-thoracic area.
Reduced Ingestion of Sweetened Milk Induced by Interleukin-1 and Lipopolysaccharide Is Associated with Induction of Cyclooxygenase-2 in Brain Endothelia
Authors: Dunn Adrian J. , Swiergiel Artur H. , Zhang Hao , Quan Ning
Published: October 2006

Previous studies have shown that interleukin-1 (IL-1) and lipopolysaccharide (LPS) administration to animals induces behavioral changes, including a reduction in feeding. These effects of IL-1 and LPS have been shown to be sensitive to inhibitors of cyclooxygenase (COX). Objectives: To determine the relationships between induction of COX-2 in the brain with IL-1β- and LPS-induced changes in body temperature, plasma corticosterone and feeding. Methods: Mice were injected with intraperitoneal doses of IL-1β and LPS that decreased feeding. The induction of COX-2 was studied immunocytochemically in the brain, in parallel with core body temperature, the drinking of sweetened milk, and plasma concentrations of corticosterone. Results: COX-2 immunoreactivity (ir) was sparse in the brains of the untreated mice, but IL-1β and LPS both increased its expression. This COX-2 induction appeared to be confined to blood vessels, and was not markedly region specific. Induction was evident 30 min after IL-1 or LPS, and was greater at 90 than at 30 min. COX-2-ir in the parenchyma did not change significantly. Thus induction of COX-2 occurred in brain endothelia in parallel with the reduction in feeding. This is consistent with the previously determined sensitivity of IL-1-induced changes in feeding to selective COX-2 inhibitors, and the responses to IL-1 in COX-2-deficient mice. The time courses of the IL-1- and LPS-induced increases in plasma corticosterone paralleled those in the reduction in milk drinking, however, the changes in body temperature appeared later. Conclusions: Endothelial COX-2 may be involved in IL-1- and LPS-induced decreases in milk drinking, and possibly in the HPA axis activation. The decreased milk drinking may occur when IL-1 and LPS bind to receptors on brain endothelial cells subsequently inducing COX-2 and the production of prostanoids which elicit the reductions in milk drinking. Thus the behavioral effects of peripherally administered IL-1 and LPS appear to be mediated by multiple mechanisms, including endothelial COX-2, and vagal afferents.
Ethnic Differences in Key Candidate Genes for Spontaneous Preterm Birth: TNF-α and Its Receptors
Authors: Menon Ramkumar , Velez Digna R. , Thorsen Poul , Vogel Ida , Jacobsson Bo , Williams Scott M. , Fortunato Stephen J.
Published: October 2006

Objectives: Spontaneous preterm birth (PTB) has a significant ethnic disparity with people of African descent having an almost 2-fold higher incidence than those of European descent in the United States. This disparity may be caused by differences in the distribution of genetic risk factors. The objective of this study is to examine genetic differences between African-Americans and European Americans for single nucleotide polymorphisms (SNPs) in candidate genes for PTB. Methods: We examined patterns of variation in 19 SNPs in 3 candidate genes for preterm birth: TNF-α, TNF-receptor 1 and TNF-receptor 2. Allele, genotype and haplotype frequencies were compared between African-Americans (AA) and European-Americans (EA) in cases and controls separately. Both maternal and fetal genotypes were studied, as it is unclear whether one or both of these are important in the etiology of PTB. Results: The vast majority of the SNPs differed significantly between ethnic groups, although there are only a few suggestive results comparing cases and controls within an ethnic group. For TNF-α, four of six SNPs; for TNF-R1, 5/6; and for TNF-R2, 6/7 showed significant differences between ethnic groups in either allele and/or genotype frequency. Conclusions: Our data demonstrate highly significant genetic differences between ethnic groups in genes that may play a role in the risk of PTB.
The Echinocandins: Comparison of Their Pharmacokinetics, Pharmacodynamics and Clinical Applications
Authors: Wagner Claudia , Graninger Wolfgang , Presterl Elisabeth , Joukhadar Christian
Published: October 2006

Caspofungin, micafungin and anidulafungin are three drugs of the echinocandin class of antifungals available for intravenous treatment of invasive candidiasis and aspergillosis. They exhibit high in vitro and in vivo activities against Candida spp. and Aspergillus spp. In various clinical studies investigating candidemia and invasive candidiasis, Candida esophagitis, and fever in neutropenia, the clinical efficacy of the echinocandin tested was similar to that of established antifungals. Antifungal activity against strains no longer susceptible to conventional antifungal agents, such as fluconazole and amphotericin B suggests that echinocandins can be used as salvage therapy in life-threatening fungal infections. There is no cross-resistance to other antifungals. Excellent safety and tolerability of treatment with caspofungin has been documented over a total of 4.3 million patient days. Echinocandins are poor substrates of the cytochrome P450 enzyme family and can be safely co-administered with most drugs without the need for dosage adaptation. No dose reduction is required in renal impairment. A reduction in the daily maintenance dose has been recommended for caspofungin, but not for micafungin and anidulafungin in patients presenting with mild to moderate hepatic failure.
Neonatal Diabetes: How Research Unravelling the Genetic Puzzle Has both Widened Our Understanding of Pancreatic Development whilst Improving Children’s Quality of Life
Authors: Shield Julian P.H.
Published: October 2006

It has become increasingly apparent over the last few years that the seemingly ubiquitous auto-immune aetiology to pre-pubertal diabetes does not apply to those diagnosed under 6 months of age. In this age group, disease appears, in the vast majority of cases, to be conferred by single gene disorders mainly related to pancreatic development. The unravelling of these disorders has resulted in a far greater understanding of pancreatic development and some startling changes in treatment, resulting in improved quality of life and diabetes control. The progress made in our scientific and clinical understanding of these extremely rare diseases is a perfect example of how studying seemingly rare illnesses can improve our overall knowledge of much more common conditions.
Leydig-Cell Tumour in Children: Variable Clinical Presentation, Diagnostic Features, Follow-Up and Genetic Analysis of Four Cases
Authors: Petkovic Vibor , Salemi Souzan , Vassella Erik , Karamitopoulou-Diamantis Evanthia , Meinhardt Udo J. , Flück Christa E. , Mullis Primus-E.
Published: October 2006

Background: Testicular tumours are relatively uncommon in infants and children, accounting for only 1–2 % of all paediatric solid tumours. Of these approximately 1.5% are Leydig-cell tumours. Further, activating mutations of the luteinizing hormone receptor gene (LHR), as well as of the G protein genes, such as Gsalpha (gsp) and Gialpha (gip2) subunits, and cyclin-dependent kinase gene 4(CDK4) have been associated with the development of several endocrine neoplasms. Aims/Methods: In this report, the clinical variability of Leydig-cell tumours in four children is described. The LHR-, gsp-, gip2- and CDK4 genes were investigated to establish the possible molecular pathogenesis of the variable phenotype of the Leydig-cell tumours. Results: No activating mutations in these genes were found in the four Leydig-cell tumours studied. Therefore, the absence of activating mutations in LHR, as well as in both the ‘hot spot’ regions for activating mutations within the G-alpha subunits and in the regulatory ‘hot spot’ on the CDK4 genes in these tumours indicates molecular heterogeneity among Leydig-cell tumours. Conclusion: Four children with a variable phenotype caused by Leydig-cell tumours are described. A molecular analysis of all the ‘activating’ genes and mutational regions known so far was performed, but no abnormalities were found. The lessons learnt from these clinically variable cases are: perform ultrasound early and most importantly, consider discrepancies between testicular swelling, tumour size and androgen production.
Incidental Thyroid Carcinoma in Thyrotoxic Patients Treated by Surgery
Authors: Cakir Mehtap , Arici Cumhur , Alakus Huseyin , Altunbas Hasan , Balci Mustafa Kemal , Karayalcin Umit
Published: October 2006

Background and Aims: Thyroid malignancy detected incidentally in patients who are operated for thyrotoxicosis has been reported at different rates. The aim of this study was to investigate the rate of incidental thyroid carcinoma in thyrotoxic patients managed with surgery in our institution. Methods: Of the 375 thyrotoxic patients who had thyroid surgery between the years of 1997–2004, 70.7% were females and 29.3% were males. Among thyrotoxic patients 65.3% (n = 245) had toxic multinodular goiter (TMG), 16.8% (n = 63) had toxic adenoma (TA) and 17.9% (n = 67) had Graves’ disease. Results: Twenty-six (6.9%) of all thyrotoxic patients had thyroid carcinoma. Eighteen (7.3%) of TMG, 4 (6.3%) of TA and 4 (6%) of Graves’ disease patients had thyroid carcinoma. Histologic examination revealed 18 papillary (9 microscopic), 5 follicular, 2 hurthle cell and 1 anaplastic carcinoma. Conclusion: In our study, incidental thyroid carcinoma was found in 6.9% of subjects with thyrotoxicosis. Papillary thyroid microcarcinomas constituted 34.6% (26/9) of these newly diagnosed thyroid carcinomas. The incidence of thyroid carcinoma was not higher in subjects with Graves’ disease compared to TMG and TA. The rate of incidental thyroid carcinoma in subjects with thyrotoxicosis treated with surgery was similar to previous studies reported from different countries.
Synergistically Upregulated Interleukin-10 Production in Cocultures of Monocytes and T Cells after Stimulation with Respiratory Syncytial Virus
Authors: Kauth Marion , Grage-Griebenow Evelin , Rohde Gernot , Anhenn Olaf , Wiethege Almut , Schultze-Werninghaus Gerhard , Bufe Albrecht
Published: October 2006

Background: Respiratory syncytial virus (RSV) is known as a causal factor of severe bronchiolitis in young children. It has also been detected in patients with chronic obstructive pulmonary disease (COPD), a disease that is associated with an increased number of T cells in the bronchial mucosa. Here, we investigated the potential direct interaction between RSV and T cells and its impact on cytokine response. Methods: Purified human peripheral blood T cells were stimulated with RSV in vitro and analyzed by flow cytometry and fluorescence microscopy. Cytokine expression and release were measured in T cell cultures and in cocultures with peripheral blood monocytes as well as with alveolar macrophages from bronchoalveolar lavage fluid by quantitative real-time PCR and ELISA. Results: It was shown that RSV adhered to the surface of T cells. Stimulation of purified T cells with RSV led to a significant increase in interleukin (IL)-10 mRNA expression after 24 h. Moreover, in cocultures of T cells with monocytes or alveolar macrophages, IL-10 production was synergistically upregulated 24 h after stimulation with RSV. Conclusion: These results suggest that RSV can cause an excessive IL-10 response leading to downregulation of antiviral defense mechanisms and reduced elimination of respiratory pathogens when antigen-presenting cells and T cells are simultaneously present on the site of infection. This effect may possibly contribute to high frequencies of respiratory pathogens found in patients with chronic inflammatory airway diseases associated with increased local T cell influx such as COPD.
Kernel Least-Squares Models Using Updates of the Pseudoinverse
Authors: Andelić E. , Schafföner M. , Katz M. , Krüger S. E. , Wendemuth A.
Published: October 2006

Sparse nonlinear classification and regression models in reproducing kernel Hilbert spaces (RKHSs) are considered. The use of Mercer kernels and the square loss function gives rise to an overdetermined linear least-squares problem in the corresponding RKHS. When we apply a greedy forward selection scheme, the least-squares problem may be solved by an order-recursive update of the pseudoinverse in each iteration step. The computational time is linear with respect to the number of the selected training samples.