bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent rhythmic oscillations induced by nicotine on neonatal rat hypoglossal motoneuronsin vitro
Authors: Lamanauskas Nerijus , Nistri Andrea
Published: November 2006

Patch‐clamp recording from hypoglossal motoneurons in neonatal Wistar rat brainstem slices was used to investigate the electrophysiological effects of bath‐applied nicotine (10 µm). While nicotine consistently evoked membrane depolarization (or inward current under voltage clamp), it also induced electrical oscillations (3–13 Hz; lasting for ≥ 8.5 min) on 40% of motoneurons. Oscillations required activation of nicotinic receptors sensitive to dihydro‐β‐erythroidine (0.5 µm) or methyllycaconitine (5 nm), and were accompanied by enhanced frequency of spontaneous glutamatergic events. The slight voltage dependence of oscillations and their block by the gap junction blocker, carbenoxolone, suggest they originate from electrically coupled neurons. Network nicotinic receptors desensitized more slowly than motoneuron ones, demonstrating that network receptors remained active longer to support heightened release of the endogenous glutamate necessary for enhancing the network excitability. The ionotropic glutamate receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), and the group I metabotropic receptor antagonist, (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA), suppressed oscillations, while the NMDA receptor antagonist,d‐amino‐phosphonovaleriate (APV), produced minimal depression. Nicotine‐evoked oscillations constrained spike firing at low rates, although motoneurons could still generate high‐frequency trains of action potentials with unchanged gain for input depolarization. This is the first demonstration that persistent activation of nicotinic receptors could cause release of endogenous glutamate to evoke sustained oscillations in the theta frequency range. As this phenomenon likely represented a powerful process to coordinate motor output to tongue muscles, our results outline neuronal nicotinic acetylcholine receptors (nAChRs) as a novel target for pharmacological enhancement of motoneuron output in motor dysfunction.
The cytosolic domain of APP induces the relocalization of dynamin 3 in hippocampal neurons
Authors: Meckler X. , Bertandeau E. , McNiven M. A. , Allinquant B. , Hémar A.
Published: November 2006

Amyloid precursor protein (APP) has been the subject of intense research to uncover its implication in Alzheimer's disease. Its physiological function is, however, still poorly understood. Herein, we investigated its possible influence on the development of cultured hippocampal neurons. A peptide corresponding to the APP intracellular domain linked to a cell‐penetrating peptide was used to alter the interactions of APP with its cytosolic partners. This treatment promoted the concentration of the cytosolic GTPase dynamin 3 (Dyn3) in neurite segments when most untreated cells displayed a homogenous punctate distribution of Dyn3. The Dyn3‐labelled segments were excluded from those revealed by APP staining after aldehyde fixation. Interestingly, after aldehyde fixation MAP2 also labelled segments excluded from APP‐stained segments. Thus APP is also a marker for the spacing pattern of neurites demonstrated by Taylor & Fallon (2006)J. Neurosci., 26, 1154–4463.
Mechanism of progesterone neuroprotection of rat cerebellar Purkinje cells following oxygen–glucose deprivation
Authors: Ardeshiri A. , Kelley M. H. , Korner I. P. , Hurn P. D. , Herson P. S.
Published: November 2006

The survival of rat Purkinje cell (PCs) cerebellar cultures was used to test the hypothesis that progesterone is protective against oxygen–glucose deprivation through potentiation of GABAA receptor activity. Electrophysiological recordings confirm that PCs develop robust excitatory and inhibitory synapses in culture. Exposure of cultured PCs to increasing concentrations of progesterone during oxygen–glucose deprivation revealed a concentration‐dependent protection by progesterone, with significant protection observed at physiological concentrations, as low as 10 nm. The concurrent application of the GABAA receptor antagonist picrotoxin (100 µm) completely abolished the neuroprotection afforded by progesterone, indicating that progesterone is neuroprotective through activation of GABAA receptors. Progesterone potentiates GABAA receptor activity indirectly through its metabolites, such as allopregnanolone (ALLO). Therefore, ALLO was applied to PC cultures and was observed to produce significant protection at all concentrations tested, from 10 to 1000 nm. Finally, the inhibition of progesterone metabolism with finasteride abolished the protection afforded by progesterone without having any effect on the neuroprotection caused by ALLO. These data indicate that progesterone protects cerebellar PCs at physiological concentrations through a GABA‐active metabolite.
Age‐related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease
Authors: Colebrooke Rebecca E. , Humby Trevor , Lynch Patrick J. , McGowan Daniel P. , Xia Jing , Emson Piers C.
Published: November 2006

Dopamine cytotoxicity is thought to contribute towards the selective loss of substantia nigra pars compacta dopamine neurons and disease progression in Parkinson's disease. However, the long‐term toxicity of dopamine in vivo has not previously been established. The vesicular monoamine transporter 2 (VMAT2) sequesters monoamines into synaptic vesicles, a process that, in addition to being important in normal transmission, may also act to keep intracellular levels of monoamine neurotransmitters below potentially toxic thresholds. The homozygous VMAT2‐hypomorphic mouse has an insertion in the VMAT2 gene (Slc18a2). Consequently, VMAT2‐deficient mice (VD–/–) have an ∼ 95% reduction in VMAT2 expression and an equivalent level of dopamine depletion in the striatum which results in moderate motor impairment. Here, we show that L‐DOPA induces locomotor hyperactivity in VD–/– mice and reverses the deficit in motor coordination and balance as tested with the rotarod. We report that evidence for cytosolic accumulation of dopamine in substantia nigra neurons in these mice is two‐fold: firstly, there is reduced phosphorylation of tyrosine hydroxylase at the residue associated with catechol feedback inhibition; and, secondly, there are increased rates of dopamine turnover at 6, 12 and 24 months of age. These animals exhibit a progressive decline in striatal monoamine levels and rotarod performance with increasing age. However, despite these data, there was no loss of nigral dopamine neurons as estimated by quantification of tyrosine hydroxylase‐immunoreactive cells in the substantia nigra pars compacta of old VD–/– mice (24‐month‐old), implying that these age‐dependent manifestations may be due to senescence alone.
dextro‐Naloxone orlevo‐naloxone reverses the attenuation of morphine antinociception induced by lipopolysaccharide in the mouse spinal cord via a non‐opioid mechanism
Authors: Wu Hsiang‐En , Sun Han‐Sen , Cheng Caleb W. , Terashvili Maia , Tseng Leon F.
Published: November 2006

Glial stimulation by intrathecal injection of lipopolysaccharide (LPS) attenuated the tail‐flick inhibition produced by morphine given intrathecally in the spinal cord of the male CD‐1 mice. The phenomenon has been defined as antianalgesia. The effects ofdextro‐naloxone orlevo‐naloxone on the attenuation of morphine‐produced tail‐flick inhibition induced by LPS were then studied. Pretreatment withdextro‐naloxone orlevo‐naloxone reversed the attenuation of the morphine‐produced tail‐flick inhibition induced by LPS. Pretreatment withdextro‐naloxone orlevo‐naloxone alone did not affect the morphine‐produced tail‐flick inhibition. It is concluded thatdextro‐naloxone andlevo‐naloxone block the LPS‐induced antianalgesia against morphine antinociception via a non‐opioid mechanism.
Lack of effects of GHB precursors GBL and 1,4‐BD following i.c.v. administration in rats
Authors: Carter Lawrence P. , Koek Wouter , France Charles P.
Published: November 2006

Gamma‐hydroxybutyrate (GHB) is used therapeutically and recreationally worldwide. Since the scheduling of GHB by the USA and the United Nations in 2000–2001, the recreational use of GHB precursors has reportedly increased. The aim of this study was to examine if potency differences of GHB and GHB‐like compounds are due to their blood–brain barrier permeability. The effects of peripheral and central administration of GHB, GHB precursors gamma‐butyrolactone (GBL) and 1,4‐butanediol (1,4‐BD), and the gamma‐aminobutyric acid (GABA)B receptor agonist baclofen on schedule‐controlled responding were examined in rats. GHB and baclofen were 276‐ and 253‐fold more potent, respectively, after intracerebroventricular (i.c.v.) administration than after intraperitoneal (i.p.) administration, whereas GBL and 1,4‐BD, up to a dose of 1780 µg were without effect after i.c.v. administration. These data suggest that GBL and 1,4‐BD are not metabolically converted to GHB in the brain, that enhanced brain penetration cannot account for potency differences between compounds, and that baclofen, like GHB, can readily cross the blood–brain barrier.
Mapping continuous neuronal activation without an ON–OFF paradigm: initial results of BOLD ceiling fMRI
Authors: Haller Sven , Wetzel Stephan G. , Radue Ernst W. , Bilecen Deniz
Published: November 2006

Standard functional magnetic resonance imaging (fMRI) requires alternations between activation (ON) and baseline (OFF) periods to map the haemodynamic response to neuronal activation. Consequently, standard fMRI cannot map continuous activations in conditions like tinnitus without an ON–OFF paradigm. We present a novel approach to fMRI that allows mapping of continuous neuronal activation. Compared with standard fMRI, we introduced the application of CO2 as potent vasodilator. CO2 induces a ‘global’ blood oxygenation level‐dependent (BOLD) response. The neurovascular coupling in conjunction with the limited cerebral vasodilation implies a limitation or ceiling of the BOLD response. We hypothesize that active areas exhibit a reduced CO2‐induced ΔBOLD due to pre‐existing ‘local’ task‐induced BOLD response. This putative reduction in ΔBOLD might be exploited for mapping of continuous neuronal activation. BOLD ceiling fMRI was tested in the auditory system. Six healthy subjects performed three runs: only continuous monaural auditory; only 10% CO2; simultaneous auditory and CO2 stimulation. First, we demonstrated the ceiling of ΔBOLD during continuous auditory activation. According to the known predominantly contralateral auditory processing, monaural auditory stimulation reduced predominantly contralateral (0.41 ± 0.13%; P < 0.00001) and significantly less (P < 0.0001) ipsilateral ΔBOLD (0.33 ± 0.17%; P < 0.00001). The non‐auditory area was not affected. Second, this BOLD ceiling was exploited to generate an initial activation map of continuous auditory activation (ON period). In contrast to standard fMRI, an OFF period without neuronal activation was not required. BOLD ceiling fMRI is proposed as a complement to standard fMRI for those conditions where ON–OFF paradigms are impossible.
Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice
Authors: Noaín Daniela , Avale M. Elena , Wedemeyer Carolina , Calvo Daniel , Peper Marcela , Rubinstein Marcelo
Published: November 2006

The dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the extremely polymorphic nature of the human gene and the genetic association with attention deficit and hyperactivity disorder (ADHD). Several efforts have been undertaken to determine the D4R expression pattern in the brain using immunohistochemistry, binding autoradiography and in situ hybridization, but the overall published results present large discrepancies. Here, we have explored an alternative genetic approach by studying bacterial artificial chromosome (BAC) transgenic mice that express enhanced green fluorescent protein (EGFP) under the transcriptional control of the mouse dopamine D4 receptor gene (Drd4). Immunohistochemical analysis performed in brain sections of Drd4‐EGFP transgenic mice using an anti‐EGFP polyclonal antibody showed that transgenic expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral agranular portions. In addition, discrete groups of Drd4‐EGFP labelled neurons were observed in the anterior olfactory nucleus, ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD.
Vaccination of Alzheimer's model mice with Aβ derivative in alum adjuvant reduces Aβ burden without microhemorrhages
Authors: Asuni Ayodeji A. , Boutajangout Allal , Scholtzova Henrieta , Knudsen Elin , Li Yong Sheng , Quartermain David , Frangione Blas , Wisniewski Thomas , Sigurdsson Einar M.
Published: November 2006

Immunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders but certain adverse reactions need to be overcome. The meningoencephalitis observed in the first AD vaccination trial was likely related to excessive cell‐mediated immunity caused by the immunogen, amyloid‐β (Aβ) 1–42, and the adjuvant, QS−21. To avoid this toxicity, we have been using Aβ derivatives in alum adjuvant that promotes humoral immunity. Other potential side effects of immunotherapy are increased vascular amyloid and associated microhemorrhages that may be related to rapid clearance of parenchymal amyloid. Here, we determined if our immunization strategy was associated with this form of toxicity, and if the therapeutic effect was age‐dependent. Tg2576 mice and wild‐type littermates were immunized from 11 or 19 months and their behaviour evaluated prior to killing at 24 months. Subsequently, plaque‐ and vascular‐Aβ burden, Aβ levels and associated pathology was assessed. The therapy started at the cusp of amyloidosis reduced cortical Aβ deposit burden by 31% and Aβ levels by 30–37%, which was associated with cognitive improvements. In contrast, treatment from 19 months, when pathology is well established, was not immunogenic and therefore did not reduce Aβ burden or improve cognition. Significantly, the immunotherapy in the 11–24 months treatment group, that reduced Aβ burden, did not increase cerebral bleeding or vascular Aβ deposits in contrast to several Aβ antibody studies. These findings indicate that our approach age‐dependently improves cognition and reduces Aβ burden when used with an adjuvant suitable for humans, without increasing vascular Aβ deposits or microhemorrhages.
Diagnostic precision of magnetic resonance imaging for preoperative prediction of the circumferential margin involvement in patients with rectal cancer
Authors: Purkayastha S. , Tekkis P. P. , Athanasiou T. , Tilney H. S. , Darzi A. W. , Heriot A. G.
Published: November 2006

Objective  Circumferential margin involvement (CMI) is an important prognostic indicator for patients with rectal cancer. This meta‐analysis aims at evaluating the diagnostic precision of magnetic resonance imaging (MRI) for the preoperative evaluation of CMI in patients with rectal cancer.

Method  Quantitative meta‐analysis was performed comparing MRI against histology after total mesorectal excision. Sensitivity, specificity and diagnostic odds ratio (DOR) were calculated for each study. Summary receiver operating characteristic (SROC) curves and subgroup analysis were undertaken. Study quality and heterogeneity were evaluated. Meta‐regression meta‐analysis was used to evaluate the significance of the difference in relative DORs.

Results  Nine studies evaluating 529 patients were included. Pooled results showed an overall sensitivity and specificity for MRI detecting CMI preoperatively of 94% and 85% respectively. The SROC analysis demonstrated an overall weighted area under the curve (AUC) of 0.92 (DOR 57.21, 95% CI 18.21–179.77), without significant heterogeneity between the studies (Q‐value 14.66, P = 0.06). Good study quality further increased the sensitivity and specificity of MRI. The use of a 1.5 Tesla coil, a phased array coil and the inclusion of two interpreters also resulted in high preoperative diagnostic precision. Meta‐regression meta‐analysis showed a significant difference in the DOR for studies published in or since 2003 (P = 0.019).

Conclusion  Magnetic resonance imaging can accurately predict CMI preoperatively for rectal cancer in single units and this is reproducible across different centres. This strategy has important implications for selection of patients for adjuvant therapy prior to surgery.
Trends in colorectal cancer survival following the 2‐week rule
Authors: Walsh S. R. , Gilson N. L. , Brown K. , Novell J. R.
Published: November 2006

Objective  The 2‐week rule has reduced waiting times for a specialist opinion among patients with a suspected malignancy. We aimed at assessing the effect of this rule on colorectal cancer survival.

Method  Patients diagnosed with colorectal cancer before (group 1) and after (group 2) the introduction of the 2‐week rule were identified from a prospective database. Emergency patients were excluded. Overall 2‐year survival for each group was calculated using the Kaplan–Meier method and compared using the log‐rank test.

Results  Waiting times fell from 26 to 21 days (P =0.22). There was no significant difference in 2‐year survival between the groups (hazard ratio 1.1; P = 0.56). There was a slight divergence between the survival curves at 2 years.

Conclusion  There has been no improvement in 2‐year survival from colorectal cancer following the introduction of the 2‐week rule.
Prioritization of colorectal referrals: a review of the 2‐week wait referral system
Authors: Rai S. , Kelly M. J.
Published: November 2006

Objective  The 2‐week wait (TWW) fast‐track referral system for patients suspected of having colorectal cancer (CRC) has fallen well short of its expectations of streamlining prioritization of colorectal referrals. Our study reviews most of the audits/studies that have been published on the system as its inception. Our aim was to identify where the shortcomings are and also to review the various alternatives that have recently been put forward.

Method  All articles on the TWW system published in mainstream peer reviewed journals were reviewed, as were all the abstracts on the system presented at the Association of Coloproctology and the British Society of Gastroenterology meetings. Implementation, compliance with guidelines, cancer detection rate, impact on waiting times and the overall effectiveness of the system are evaluated.

Results  While the implementation of the system has been generally robust in most centres, the compliance with guidelines has been poor. This coupled with the inherently poor specificity of the system has resulted in a poor (and decreasing) cancer detection rate and a steadily growing volume of the hospital referrals. The system has been shown to have an adverse impact on the waiting times for routine colorectal referrals – a group that contributes significantly to the total number of CRC detected.

The various alternatives to the TWW system that have been proposed recently, including our own, are discussed.

Conclusion  The shortcomings of the TWW system in its original form have now been demonstrated beyond doubt. What is needed is a fresh approach to find a cost effective and viable alternative in a climate of increased expectations and finite resources.
Figuring the Prison: Prerequisites of Torture at Abu Ghraib1
Authors: Sexton Jared , Lee Elizabeth
Published: November 2006

This article presents a critique of prevailing left‐of‐center journalism and academic scholarship on the revelation of torture of Iraqi prisoners of war by United States military personnel at Abu Ghraib in the spring of 2004. We argue that the resulting discourse suffers from a certain critical bankruptcy in its failure to think about the nature of imprisonment as such. This failure is an effect of two procedures: (1) a narrowing of the field of inquiry that relies on the metonymic reduction of imprisonment through and as the practices of torture, and (2) a reification of the prison that both relies upon and displaces the racialization of imprisonment as an institution of black spatial containment and social control. In response, we call for a renewed understanding of and appreciation for the singularity of racial slavery and its afterlife in future research on carceral formations in and beyond the US.
A DYNAMICAL ANALYSIS OF ALTERNATIVE FORMS OF AGRICULTURAL LAND TENURE
Authors: Commendatore Pasquale , Currie Martin
Published: November 2006

This paper explores a dynamic model of an agricultural sector in which farms are leased to cultivators on fixed rent contracts or on sharecropping contracts and in which cultivators are subject to credit rationing by banks. The model, which can exhibit complex dynamics, is used to compare the two pure forms of land tenure and to explore some implications of the coexistence of both types of tenure. The central conclusion from the dynamic simulations is that, contrary to the conventional proposition based on static analysis, both landowners and cultivators may be better‐off under sharecropping.
THE EVOLUTION OF PRODUCTIVITY GAPS AND SPECIALIZATION PATTERNS
Authors: Los Bart , Verspagen Bart
Published: November 2006

This paper presents an industry‐level model of growth and trade, in which evolving specialization patterns are the endogenous result of innovation, international technology spillovers, learning‐by‐doing and balance of payments‐restricted growth. Differences between industries with regard to their share in consumption are shown to reinforce or mitigate the effects of specialization on aggregate productivity convergence patterns, depending on other parameters. The implications of the model are studied by means of simulation analyses for a wide range of parameter configurations.
INTEREST RATE PEGS, WEALTH EFFECTS AND PRICE LEVEL DETERMINACY
Authors: Annicchiarico Barbara , Marini Giancarlo
Published: November 2006

This paper analyses the issue of price level determinacy in an optimizing general equilibrium model with overlapping generations. It is shown that under a pure interest rate peg wealth effects rule out nominal indeterminacy but give rise to multiple equilibria.
DEMOGRAPHY IN MACROECONOMIC MODELS: WHEN LABOUR SUPPLY MATTERS FOR ECONOMIC CYCLES
Authors: Manfredi Piero , Fanti Luciano
Published: November 2006

The issue of the onset of Malthusian cycles is investigated by means of a demo‐economic model incorporating the age structure of the population. It is shown that the delayed recruitment into the labour force is a major source of demo‐economic instability, potentially leading to sustained oscillations. We also compare different modelling strategies for age structure, by showing that the results of our general model are borne out by those provided by a simpler model, based on a representation of age structure via time delays, which allows a deeper mathematical analysis. This suggests that simplified delay models may be of great help in understanding the qualitative properties of complex age structure models.
CD4 count and viral load time‐courses in patients treated with highly active antiretroviral therapy and association with the CDC staging system
Authors: Collazos J , Knobel H , Casado JL ,   on behalf of the Grupo Español para el Estudio Multifactorial de la Adherencia (GEEMA)
Published: November 2006

Objectives

The aim of the study was to analyse CD4 cell count and viral load dynamics in patients undergoing antiretroviral therapy and their association with the Centers for Disease Control and Prevention (CDC) classification system.

Methods

CD4 cell count and viral load were determined in 2982 patients who were classified according to clinical and immunological CDC stages. Measurements were carried out at baseline and at the 3rd, 6th and 12th months.

Results

Clear differences in the immunological and virological responses to therapy were observed depending on the CDC stage, with better results associated with less advanced stages. There was a marked parallelism in the CD4 cell count curves of the different CDC stages over the year of follow up, in both naïve and experienced patients, indicating that the increase in CD4 cell count at each time‐point was similar for all clinical and immunological CDC stages. However, as the baseline values were closely associated with CDC stage, the CD4 cell counts finally reached were clearly dependent on CDC stage. The highest virological responses were observed during the initial 3 months, particularly in naïve patients, but whereas naïve patients showed additional increases up to the 6th month experienced patients reached a plateau at the 3rd month. The CD4 increases were also higher during the initial 3 months but persisted during the year of follow‐up.

Conclusion

Both clinical and immunological CDC stages at baseline are highly predictive of the immunological and virological response to therapy, a finding that could have clinical implications.
Impact of highly active antiretroviral therapy on the maturation of anti‐HIV‐1 antibodies during primary HIV‐1 infection
Authors: Adalid‐Peralta L , Grangeot‐Keros L , Rudent A , Ngo‐Giang‐Huong N , Krzysiek R , Goujard C , Deveau C , Le Gall M , Meyer L , Emilie D , Rouzioux C ,   for the PRIMO and ANRS Study Group
Published: November 2006

Objectives

To study the impact of highly active antiretroviral therapy (HAART) on isotype switching and avidity maturation of HIV‐1‐specific immunoglobulin G (IgG) in patients with primary HIV‐1 infection (PHI).

Methods

We studied the emergence and the evolution of anti‐HIV IgG antibodies by quantitative immunoblotting to analyse IgG subclasses and IgG avidity. Serum samples were obtained from 16 PHI patients from the French PRIMO Cohort Study at various points in the first year of infection: eight patients received no treatment (group I), and eight patients received efficient HAART (group II) during the study period.

Results

Early initiation of HAART in PHI patients partially prevented an increase in anti‐HIV‐1 IgG levels. Within IgG subclasses, the amount of anti‐HIV‐1 IgG1 gradually increased with time in both groups, although levels remained lower in treated patients. The anti‐p24 IgG2 level was always lower in group II. We observed a decrease in anti‐p24 IgG3 over time in both groups. Treatment did not affect the maturation of HIV‐1 IgG avidity, which increased in both groups until month 3 and then remained high until the end of the 12‐month follow‐up period.

Conclusions

HAART in PHI partially prevents the emergence of HIV‐1 IgG antibodies, but does not affect the quality of these antibodies, as reflected in their isotype and avidity.
Influence of gender and HIV transmission group on initial highly active antiretroviral therapy prescription and treatment response
Authors: Fardet L , Mary‐Krause M , Heard I , Partisani M , Costagliola D ,   for the French Hospital Database on HIV
Published: November 2006

Background

The literature contains conflicting findings on the influence of gender and HIV transmission group on the initial prescription of highly active antiretroviral therapy (HAART) and its biological and clinical efficacy.

Methods

We conducted a cohort study involving 62 French hospitals. We used Cox proportional hazards models to examine whether gender and HIV transmission group influenced the timing of elective HAART initiation, and the clinical and biological response to treatment.

Results

We studied 5735 patients enrolled between January 1997 and December 2001 who did not start HAART or develop a stage C HIV‐related event during the first 3 months after inclusion. In multivariate analysis, no gender differences were found in the interval between enrolment in the database and HAART initiation, but this interval was shorter in homosexual patients than in other transmission groups; CD4 cell counts at treatment initiation were also higher in the homosexual group. The immunovirological response to treatment did not differ according to gender, but was better in homosexual patients than in patients in other categories. Injecting drug users had the weakest immunovirological responses. Clinical outcome was not related to gender or to HIV transmission group.

Conclusions

The interval between diagnosis of HIV‐1 infection and elective HAART initiation was not influenced by gender. However, homosexual patients had higher CD4 cell counts than other patients at treatment initiation, and also had better immunovirological responses.
Efavirenz and chronic neuropsychiatric symptoms: a cross‐sectional case control study
Authors: Rihs TA , Begley K , Smith DE , Sarangapany J , Callaghan A , Kelly M , Post JJ , Gold J
Published: November 2006

Objective

The aim of the study was to investigate symptoms of long‐term central nervous system (CNS) toxicity in HIV‐positive patients treated with efavirenz (EFV).

Methods

We carried out a single‐centre, cross‐sectional case–control study comparing patients treated with EFV for at least 6 months with a matched control group. Self‐administered, standardized questionnaires including the Depression, Anxiety and Stress Scales (DASS), the Cognitive Failures Questionnaire (CFQ) and a questionnaire on unusual dreams, insomnia, fatigue, dizziness, depersonalization and derealization were administered.

Results

Data for 32 matched pairs were analysed. Significantly higher total stress scores (P=0.008) were found in the EFV group. Of the patients in this group, 19% also reported severe to extremely severe levels of stress (P=0.014), indicating increased difficulty in relaxing, and being more irritable, impatient, agitated and easily upset. Nineteen per cent of patients treated with EFV also reported severe levels of anxiety (P=0.059) as assessed with the DASS scale. This patient group also reported a higher rate of unusual dreams (P=0.049). No significant differences between groups were found for measures of cognitive impairments, fatigue, dizziness, derealization or depersonalization.

Conclusion

EFV‐treated patients reported higher levels of severe stress and anxiety as well as a higher rate of unusual dreams than patients not treated with EFV. These differences may be an expression of persisting CNS side effects in patients who remain on EFV for a prolonged period.
Antiretroviral treatment and age‐related comorbidities in a cohort of older HIV‐infected patients
Authors: Orlando G , Meraviglia P , Cordier L , Meroni L , Landonio S , Giorgi R , Fasolo M , Faggion I , Riva A , Zambelli A , Beretta R , Gubertini G , Dedivitiis G , Jacchetti G , Cargnel A
Published: November 2006

Background

The availability of several therapeutic regimens has transformed HIV infection from a life‐threatening disease into a chronic condition. Older patients (>50 years old) with HIV infection constitute a new treatment challenge in terms of the cumulative effects of ageing and antiretroviral therapy (ART).

Methods

The immunovirological effects and metabolic interactions of 48 weeks of ART in older patients followed up in three Infectious Diseases Units in Milan, Italy since 1994 were compared with those in younger controls aged 25–35 years.

Results

The 159 older patients and 118 controls enrolled in the study were comparable for HIV stage, baseline CD4 cell count and viral load but differed for mode of HIV transmission, comorbid conditions and related chronic treatments. Mean viral load decreased after 48 weeks of treatment by 2.6 log10 HIV RNA copies/mL and CD4 count increased by 137.5 cells/μL in older patients, and similar values for immunovirological effects were obtained in the young controls. The relative risk (RR) of an abnormal test in older patients was 7.33 [95% confidence interval (CI) 4.36–12.36] for glucose, 1.73 (95% CI 1.45–2.07) for total cholesterol, 1.56 (95% CI 1.22–2.0) for high‐density lipoprotein cholesterol, 1.26 (95% CI 1.02–1.56) for triglycerides, 6.48 (95% CI 4.36–9.66) for serum creatinine, and 0.45 (95% CI 0.35–0.58) for ALT. Moderate/severe liver and renal toxicities were recorded in the older patients but not in the controls. The tolerability of ART did not differ between the older patients and the controls. Thirty‐nine new cardiovascular, endocrine‐metabolic and neuralgic disorders (24.52 per 100 person‐years) were diagnosed in the older patients and four (3.39 per 100 person‐years) in the controls (P<0.0001).

Conclusions

Diseases induced by, or related to, the toxic effects of antiretrovirals interact with age‐specific health profiles, raising new questions and challenges. Comparative epidemiological studies, research studies addressing specific questions and surveillance are needed to answer the questions that arise in clinical monitoring.
Long‐term treatment with pramipexole in restless legs syndrome
Authors: Montplaisir J. , Fantini M. L. , Desautels A. , Michaud M. , Petit D. , Filipini D.
Published: November 2006

The aim of the present study was to look at the long‐term efficacy and side effects profiles of pramipexole in a large cohort of drug naïve patients with regard to dopaminergic medications. In all, 195 consecutive restless legs syndrome (RLS) patients who were prescribed pramipexole more than 1 year previously, agreed to undergo a telephone interview to assess both the efficacy and side effects of pramipexole. Forty‐three patients had discontinued pramipexole: 20 because of side effects, six because of a lack of efficacy, six for both and 11 for other reasons. Patients who continued pramipexole for more than 1 year (n = 152) reported a mean decrease in RLS symptoms severity of 80.9% (SD = 19.6%). At the onset of treatment, the most common side effects were nausea (30%), tiredness (9%), dizziness (8%), headache (4%), insomnia (3%), dry mouth (2%), difficulty to concentrate (1.3%) and sleepiness (0.7%), At 30 months, most patients (n = 124/152; 81.6%) reported an absence of side effects of pramipexole. None of the adverse effects occurred in more than 5% of patients at follow‐up. The present study confirms, in a large cohort of unselected patients, that pramipexole is effective and safe in the long‐term treatment of RLS.
Dissociated small hand muscle atrophy in aging: the ‘senile hand’ is a split hand
Authors: Voermans N. C. , Schelhaas H. J. , Munneke M. , Zwarts M. J.
Published: November 2006

The term ‘split hand’ refers to a pattern of dissociated atrophy of hand muscles and was first described in ALS. We hypothesize that this phenomenon also occurs in ‘normal’ aging. We investigated healthy subjects of different ages and found a progressive dissociation in atrophy of the hand muscles, as measured with compound muscle action potential amplitudes, with increasing age. Different possible causes of this progressive dissociation are discussed. It might be related to preferential use of thenar muscles in humans, which render these muscles and their motor neurons more susceptible to oxidative stress. In addition, a difference in intrinsic susceptibility to oxidative stress might be involved. The relation between normal age‐related muscle loss (sarcopenia) and the pathologic loss in motor neuron disease is discussed.
Gene expression profiling in the human middle cerebral artery after cerebral ischemia
Authors: Vikman P. , Edvinsson L.
Published: November 2006

We have investigated the gene expression in human middle cerebral artery (MCA) after ischemia. Ischemic stroke affects the perfusion in the affected area and experimental cerebral ischemia results in upregulation of vasopressor receptors in the MCA leading to the ischemic area. We obtained human MCA samples distributing to the ischemic area, 7–10 days post‐stroke. The gene expression was examined with real‐time polymerase chain reaction (PCR) and microarray, proteins were studied with immunohistochemistry.We investigated genes previously shown to be upregulated in animal models of cerebral ischemia (e.g. ETA, ETB, AT1, AT2, and 5‐HT2A/1B/1D). Their mRNA expression was increased compared with controls, consistent with findings in experimental stroke. Immunohistochemistry showed upregulation of the receptors localized on the smooth muscle cells. The gene expression was profiled with microarray and seven genes chosen for further investigation with real‐time PCR; ELK3, LY64, Metallothionin IG, POU3F4, Actinα2, RhoA and smoothelin. Six of these were regulated the same way when confirming array expression with real‐time PCR. Gene expression studies in the human MCA leading to the ischemic region is similar to that seen after MCA occlusion in rats. We found new genes that support the dynamic changes that occur in the MCA distributing to the ischemic region.
Fatigue and sleep disturbance in multiple sclerosis
Authors: Kaynak H. , Altintaş A. , Kaynak D. , Uyanik Ö. , Saip S. , Ağaoğlu J. , Önder G. , Siva A.
Published: November 2006

Considering the association of sleep disturbance and fatigue in multiple sclerosis (MS), we investigated the presence of sleep disturbances that may be related to fatigue by using objective and subjective measures. We included 27 MS patients with fatigue, 10 MS patients without fatigue and 13 controls. The Pittsburgh sleep quality index score showed significant differences between patient groups and controls. Beck depression inventory scores were significantly higher in fatigued than non‐fatigued patients. Comparison of patient groups and controls revealed significant differences for time in bed, sleep efficiency index, sleep continuity index, wake time after sleep onset, total arousal index and periodic limb movement arousal index. Our study confirms that MS causes sleep fragmentation in terms of both macro and microstructure. Fatigue in MS could be partially explained by disruption of sleep microstructure, poor subjective sleep quality and depression.
High‐fat diet impairs hippocampal neurogenesis in male rats
Authors: Lindqvist A. , Mohapel P. , Bouter B. , Frielingsdorf H. , Pizzo D. , Brundin P. , Erlanson‐Albertsson C.
Published: November 2006

High fat diets and obesity pose serious health problems, such as type II diabetes and cardiovascular disease. Impaired cognitive function is also associated with high fat intake. In this study, we show that just 4 weeks of feeding a diet rich in fat ad libitum decreased hippocampal neurogenesis in male, but not female, rats. There was no obesity, but male rats fed a diet rich in fat exhibited elevated serum corticosterone levels compared with those fed standard rat chow. These data indicate that high dietary fat intake can disrupt hippocampal neurogenesis, probably through an increase in serum corticosterone levels, and that males are more susceptible than females.
Influence of levetiracetame on ictal and postictal EEG in patients with partial seizures
Authors: Tilz C. , Stefan H. , Hopfengaertner R. , Kerling F. , Genow A. , Wang‐Tilz Y.
Published: November 2006

To investigate the influence of levetiracetame (LEV) treatment on the interhemispheric seizure pattern propagation and postictal recovery of electroencephalography (EEG) background activity. Twenty‐three adult patients (age > 16 years) with pharmacoresistant focal epilepsies presenting at the Epilepsy Center Erlangen for pre‐surgical evaluation were enrolled in the study. Those eligible patients receiving only one antiepileptic drugs were recruited to the 48‐h baseline phase and, after at least two seizures, were randomized to the 7‐day treatment phase with either LEV (n = 11) or placebo (n = 12). All participants were submitted to continuous day‐and‐night video‐EEG monitoring. The daily dose of LEV was 1000 mg (500 mg bid.) on the first treatment day and was increased to 2000 mg (1000 mg bid.) from the second day onward. The EEG changes relating to the time delay of the interhemispheric seizure pattern propagation and to the postictal recovery of the background activity were analysed by computerized video‐EEG recording and compared using the non‐parameter Mann–Whitney U‐exact test (α = 0.05). A prolonged latency of the contralateral seizure pattern propagation was observed in the LEV group, whereas a more rapid propagation was observed in the placebo group (P = 0.009). Postictal generalized slowing of the background activity was recorded in 21 patients during the baseline phase. More rapid postictal recovery of the EEG background activity was observed in the LEV, but not in the placebo group (P = 0.03). This study demonstrated that LEV not only prevented the seizure pattern propagation but also helped the speedy recovery of the postictal background activity in the EEG.
The number of pregnancies is a risk factor for Alzheimer's disease
Authors: Colucci M. , Cammarata S. , Assini A. , Croce R. , Clerici F. , Novello C. , Mazzella L. , Dagnino N. , Mariani C. , Tanganelli P.
Published: November 2006

Epidemiological data show a higher prevalence of late‐onset Alzheimer's disease (AD) in women. The estrogenic deficiency in the post‐menopausal period is suspected to be the cause of the gender‐related risk of the disease, but studies on the estrogenic therapy and occurrence of AD were not consistent and sometimes contradicting. The aim of this study is to investigate whether a higher exposure to endogenous estrogens is associated with lower risk of dementia or not. Two hundred and four AD patients and 201 control women were considered. By interviews, we evaluated different variables, indirectly correlated to estrogenic natural exposure, as well as educational level and head trauma. These data were correlated in the AD group with the disease progression, as well as with the age at onset. Unexpectedly, we found a significant higher number of pregnancies in the AD than in the control group. Within the AD cases, the number of lifetime pregnancies is related to an earlier onset of the disease. As previously reported, we confirmed that the educational level is a protective factor and that major head trauma represents a risk factor in developing AD. The higher number of pregnancies and a less frequency of nulliparous women, indirectly relate the AD group to a higher estro‐progestinic exposure. These findings suggest that it is the increase of progesterone or estrogens level – and not the estrogens decrease, as previously indicated by other authors – that could play a role in the Alzheimer's pathology.
Preliminary report on effects of oxcarbazepine‐treatment on serum lipid levels in children
Authors: Franzoni E. , Marchiani V. , Cecconi I. , Moscano F. C. , Gualandi S. , Garone C. , Sarajlija J. , Malaspina E.
Published: November 2006

The aim of the present study was to assess serum lipid levels before and after treatment with oxcarbazepine (OXC) in children with epilepsy. We measured total cholesterol (TC), triglycerides (TGs) and high‐density lipoprotein cholesterol (HDL‐C) in 28 patients whereas only TC levels in 11 patients, during baseline period and at 3 months after the beginning of therapy with OXC. During baseline period, median values were: 4.38 mmol/l (IQR = 4.12–5.03) for TC levels, 1.72 mmol/l (IQR = 1.42–2.01) for HDL‐C levels and 1.54 mmol/l (IQR = 1.29–1.96) for TGs levels. At 3 months, median values were: 4.38 mmol/l (4.10–4.95) for TC levels (P < 0.05), 1.57 mmol/l (1.34–1.93) for HDL‐C levels (P < 0.005) and 1.8 mmol/l (1.23–2.34) for TGs levels (P < 0.05). Median serum lipid levels remained in the normal range, despite an increasing‐trend at 3 months of treatment with OXC. Further studies are necessary to confirm these results.
PECAM‐1, a key player in neuroinflammation
Authors: Kalinowska A. , Losy J.
Published: November 2006

Platelet endothelial cell adhesion molecule‐1 (PECAM‐1, CD31) is a 130‐kDa protein, which plays a significant role in the adhesion cascade. It is therefore involved in leucocyte endothelium interaction and in leucocyte transendothelial migration during inflammation. As neuroinflammation and subsequent blood brain barrier disruption are integral processes in many neurological disorders, PECAM‐1 and its soluble form (sPECAM‐1) have been investigated in a number of conditions, rising hopes as a potential marker of disease activity, a possible target in treatment and a prognostic factor. It has been shown that serum and CSF levels of PECAM‐1 and sPECAM‐1 are increased in patients in active stages of multiple sclerosis. Similarly, they rise in individuals after ischaemic stroke. PECAM‐1 has also been shown to be involved in the pathogenesis of Aβ‐related cerebral vascular disorders, such as Alzheimer disease. It participates in the pathomechanism of paraneoplastic neurological disorders and in neuroinflammation in NeuroAIDS. A number of experiments on animal models were carried out in order to investigate PECAM‐1 role in the above‐mentioned conditions and more, including brain trauma and nerve root injury. In this review most recent investigations on PECAM‐1 biology and its role in neuroinflammation have been described and discussed from a multidisciplinary point of view.
Localization of water‐soluble carbohydrates in wheat stems using imaging matrix‐assisted laser desorption ionization mass spectrometry
Authors: Robinson Sarah , Warburton Karen , Seymour Mark , Clench Malcolm , Thomas‐Oates Jane
Published: November 2006

The pool of endogenous water‐soluble oligosaccharides found in the stems of wheat (Triticum aestivum) is being investigated as a potential indicator of grain yield. Techniques such as liquid chromatography with mass spectrometry (LC‐MS) can profile these analytes but provide no spatial information regarding their distribution in the wheat stem. The imaging matrix‐assisted laser desorption ionization (MALDI) mass spectrometry technique has not been utilized for the analysis of oligosaccharides in plant systems previously.

Imaging MALDI mass spectrometry was used to analyse cross and longitudinal sections from the stems of Triticum aestivum.

A range of oligosaccharides up to Hex11 were observed. Water‐soluble oligosaccharides were ionized as potassiated molecules, and found to be located in the stem pith that is retained predominantly around the inner stem wall.

Imaging MALDI analyses provided spatial information on endogenous oligosaccharides present in wheat stems. The technique was found to offer comparable sensitivities for oligosaccharide detection to those of our established LC‐MS method, and has potential for broad application in studying the in situ localization of other compound types in plant material.
Linking Self‐Regulation and Risk Proneness to Risky Sexual Behavior: Pathways through Peer Pressure and Early Substance Use
Authors: Crockett Lisa J. , Raffaelli Marcela , Shen Yuh‐Ling
Published: November 2006

The linkages between self‐regulation in childhood, risk proneness in early adolescence, and risky sexual behavior in mid‐adolescence were examined in a cohort of children (N=518) from the National Longitudinal Survey of Youth. The possible mediating role of two early adolescent variables (substance use and negative peer pressure) was also examined. Self‐regulation was assessed by maternal report at ages 8–9, and risk proneness, comprising aspects of sensation seeking and decision making, was assessed by adolescent self‐report at ages 12–13. Structural equation models predicting risky sexual behavior at ages 16–17 indicated that self‐regulation operated partly through early adolescent substance use, whereas risk proneness operated through early adolescent substance use and negative peer pressure. The overall model did not differ significantly for boys and girls, although there were gender differences in the strength of particular paths. These long‐term longitudinal results support the importance of early self‐regulation and risk proneness in setting the stage for adolescent sexual risk taking and implicate substance use and negative peer pressure as processes through which risk proneness and poor self‐regulation lead to risky sexual behavior.