bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients
Authors: Regenold William T , Hisley K Calvin , Phatak Pornima , Marano Christopher M , Obuchowski Abraham , Lefkowitz David M , Sassan Amritpal , Ohri Sameer , Phillips Tony L , Dosanjh Narveen , Conley Robert R , Gullapalli Rao
Published: October 2008

Objectives:  Both diabetes mellitus and magnetic resonance image (MRI) deep white matter hyperintensities (WMHs) are more common in bipolar disorder (BD) patients than in matched controls. Deep—as opposed to periventricular—WMHs and diabetes are associated with treatment resistance and poorer outcome. This study investigated whether brain glucose metabolism by the polyol pathway—a pathway linked to nervous tissue disease in diabetes—is related to deep WMH volume and treatment resistance in BD patients.

Methods:  Volumes of fluid‐attenuated inversion recovery WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 20 nondiabetic patients with BD and nondiabetic comparison subjects with schizophrenia (n = 15) or transient neurologic symptoms (neurologic controls, n = 15).

Results:  BD patients, but not schizophrenic patients, had significantly greater volumes of deep but not periventricular WMHs compared to neurologic controls. BD subjects also had significantly greater CSF concentrations of sorbitol and fructose (the polyol pathway metabolites of glucose) compared to controls. Significant positive correlations between CSF metabolites and WMH volumes were found only in the BD group and were between deep WMH volumes and CSF sorbitol (ρ = 0.487, p = 0.029) and fructose (ρ = 0.474, p = 0.035). An index of treatment resistance correlated significantly with deep WMH volume (ρ = 0.578, p = 0.008), sorbitol (ρ = 0.542, p = 0.013), and fructose (ρ = 0.692, p = 0.001) in BD subjects but not in other subjects.

Conclusions:  This is the first reported evidence of relationships between abnormal brain glucose metabolism and both deep WMHs and treatment resistance in a group of BD patients. Further studies are necessary to determine the significance of these findings to BD pathophysiology.
Cigarette smoking in the early course of bipolar disorder: association with ages‐at‐onset of alcohol and marijuana use
Authors: Heffner Jaimee L , DelBello Melissa P , Fleck David E , Anthenelli Robert M , Strakowski Stephen M
Published: October 2008

Objectives:  Despite the high prevalence of smoking among individuals with bipolar disorder, few studies have attempted to identify correlates of smoking status in this group. We examined illness characteristics of bipolar disorder as well as co‐occurring alcohol and marijuana use as correlates of cigarette smoking, including the developmental timing of the onset of regular alcohol and cannabis use (i.e., three or more times per week for a month or more).

Methods:  Demographic and clinical characteristics of 134 patients with bipolar I disorder, the majority of whom were adolescents, who were hospitalized for their first manic episode were analyzed to identify correlates of smoking status.

Results:  A total of 61 (45.5%) of the patients were smokers at the time of their first hospitalization. Smokers were significantly more likely than nonsmokers to report recent use of marijuana (55.7% versus 18.1%) and alcohol (67.2% versus 25.4%). Among those who had ever used marijuana (48.5%) or alcohol (45.5%) regularly, current cigarette smokers reported a significantly earlier age‐at‐onset of regular use of both substances than reported by nonsmokers. Earlier age‐at‐onset of marijuana use was the only significant predictor of current smoking in a multivariate analysis. None of the bipolar disorder characteristics examined (i.e., symptom severity, age‐at‐onset of illness, rapid cycling, and psychosis) were correlated with smoking status.

Conclusions:  Smoking status in the early course of bipolar disorder is related to both current and past alcohol and marijuana use, but not to characteristics of bipolar illness. Earlier initiation of regular marijuana use is associated with an increased risk of smoking cigarettes.
Brief daily suckling shifts locomotor behavior and induces PER1 protein in paraventricular and supraoptic nuclei, but not in the suprachiasmatic nucleus, of rabbit does
Authors: Meza Enrique , Juárez Claudia , Morgado Elvira , Zavaleta Yael , Caba Mario
Published: October 2008

Nursing in the rabbit is a circadian event during which mother and pups interact for a period of < 5 min every day. Here we explored behavioral and neuronal changes in the mother by analyzing the suprachiasmatic nucleus (SCN), and oxytocinergic (OT) neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). We maintained lactating does in a light–dark cycle (lights on at 07 : 00 hours; ZT0); they were scheduled to nurse during either the day (ZT03) or the night (ZT19). Groups of intact and nursing females was perfused, one at each 4‐h point through a 24‐h cycle. We explored, by immunohistochemistry, the PER1 expression and double‐labeling, with OT antibody, of neurons in the PVN and SON at lactation on day 7. In the SCN, intact and lactating groups had peak PER1 expression at ZT11; however, there was a reduction in PER1 at peak time in the nursing groups. There was a locomotor activity rhythm with increased activity around the time of lights‐on in intact subjects and around the time of suckling in lactating does. There was an induction of PER1 in OT cells in the PVN and SON that shifted in phase with timing of nursing. We further explored the maintenance of the PER1 expression in OT cells in nursing‐deprived does and found a significant decrease at 24 and 48 h after the last nursing. We conclude that suckling induced PER1 in the PVN and SON, but not in the SCN, in nursing does, and also shifted their locomotor behavior.
Down‐regulation of protocadherin‐α A isoforms in mice changes contextual fear conditioning and spatial working memory
Authors: Fukuda Emi , Hamada Shun , Hasegawa Sonoko , Katori Shota , Sanbo Makoto , Miyakawa Tsuyoshi , Yamamoto Toshifumi , Yamamoto Hideko , Hirabayashi Takahiro , Yagi Takeshi
Published: October 2008

Diverse protocadherins (Pcdhs), which are encoded as a large cluster (composed of α, β and γ clusters) in the genome, are localized to axons and synapses. The Pcdhs have been proposed to contribute to the generation of sophisticated neural networks and to regulate brain function. To address the molecular roles of Pcdhs in regulating individual behavior, here we generated knockdown mice of Pcdh‐α proteins and examined their behavioral abnormalities. There are two alternative splicing variants of the Pcdh‐α constant region, Pcdh‐α A and B isoforms, with different cytoplasmic tails. Pcdh‐αΔBneo/ΔBneo mice, in which the Pcdh‐α B splicing variant was absent and the Pcdh‐α A isoforms were down‐regulated to approximately 20% of the wild‐type level, exhibited enhanced contextual fear conditioning and disparities in an eight‐arm radial maze. Similar abnormalities were found in Pcdh‐αΔAneo/ΔAneo mice, which lacked 57 amino acids of the Pcdh‐α A cytoplasmic tail. These learning abnormalities were, however, not seen in Pcdh‐αΔB/ΔB mice [in which the neomycin‐resistance (neo) gene cassette was removed from the Pcdh‐αΔBneo/ΔBneo alleles], in which the expression level of the Pcdh‐α A isoforms was recovered, although the Pcdh‐α B isoforms were still completely missing in the brain. In addition, the amount of 5‐hydroxytryptamine increased in the hippocampus of the hypomorphic Pcdh‐α A mutant mice but not in recovery Pcdh‐αΔB/ΔB. These results suggested that the level of Pcdh‐α A isoforms in the brain has an important role in regulating learning and memory functions and the amount of 5‐hydroxytryptamine in the hippocampus.
Medial temporal lobe structures participate differentially in consolidation of safe and aversive taste memories
Authors: De la Cruz Vanesa , Rodriguez‐Ortiz Carlos J. , Balderas Israela , Bermudez‐Rattoni Federico
Published: October 2008

Taste memories are amongst the most important kinds of memories, as adequate identification of safe and toxic edibles will determine the subject’s survival. Despite the well‐established role that the medial temporal lobe plays in consolidation of memory, specific contributions of the different regions of the temporal lobe to taste memory consolidation remain unknown. In the present report, we assessed the participation of perirhinal cortex (Ph), dorsal hippocampus (Hipp), basolateral (BLA) and central nuclei of the amygdala (CeA) in safe and aversive taste memories by means of local infusions of the protein synthesis inhibitor anisomycin in the rat. The results showed that protein synthesis in the CeA, but not BLA, is required to stabilize taste aversion memory. Surprisingly, the Ph and Hipp seem to be essential to consolidate safe taste memory. These data suggest that different networks within the temporal lobe are recruited to consolidate memory depending on the consequences associated with tastes.
Rescue of hippocampal LTP and learning deficits in a rat model of psychosis by inhibition of glycine transporter‐1 (GlyT1)
Authors: Manahan‐Vaughan Denise , Wildförster Verena , Thomsen Christian
Published: October 2008

N‐methyl‐d‐aspartate (NMDA) receptor hypofunction is believed to comprise a central factor in the cognitive symptoms of psychotic illnesses such as schizophrenia. In the MK801 model of psychosis in rats, NMDA hypofunction also occurs, and animals display a profound impairment of both hippocampus‐dependent learning and synaptic plasticity. The NMDA receptor may thus comprise a useful target for therapeutic amelioration of the symptoms of psychosis. However, direct activation of the receptor could lead to disturbed synaptic information storage. One possibility, however, is to enhance NMDA receptor function indirectly through elevation of glycine levels. We investigated the effects of inhibition of the glycine transporter‐1, GlyT1, on long‐term potentiation (LTP) and long‐term depression (LTD) in the dentate gyrus of freely behaving rats that had been treated previously with MK801. LTP, but not LTD, was impaired in MK801‐treated animals. Systemic application of the GlyT1‐inhibitor N[3‐(4’‐flurophenyl)‐3‐(4’‐phenylphenoxy) propyl]sarcosine (NFPS) rescued LTP but had no effect on LTD in MK801‐treated animals. Application of the antagonist to vehicle‐treated controls resulted in a disruption of LTP but not LTD. NFPS significantly ameliorated reference memory deficits in a radial maze that occurred following MK801 treatment. NFPS‐treated controls performed less well, however, than vehicle‐injected controls. These data support that treatment with a glycine transporter inhibitor can ameliorate deficits in both LTP and learning that occur in a rat model of psychosis, and may therefore prove a useful strategy to address cognitive disruption in psychotic illnesses. Use of the inhibitor in healthy subjects is neither beneficial to synaptic plasticity nor hippocampus‐dependent learning.
GABAA receptors present higher affinity and modified subunit composition in spinal motor neurons from a genetic model of amyotrophic lateral sclerosis
Authors: Carunchio Irene , Mollinari Cristiana , Pieri Massimo , Merlo Daniela , Zona Cristina
Published: October 2008

Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the selective degeneration of motor neurons in the spinal cord, brainstem and cerebral cortex. In this study we have analysed the electrophysiological properties of GABAA receptors and GABAA alpha1 and alpha2 subunits expression in spinal motor neurons in culture obtained from a genetic model of ALS (G93A) and compared with transgenic wild type SOD1 (SOD1) and their corresponding non transgenic litter mates (Control). Although excitotoxic motor neuron death has been extensively studied in relation to Ca2+‐dependent processes, strong evidence indicates that excitotoxic cell death is also remarkably dependent on Cl− ions and on GABAA receptor activation. In this study we have analysed the electrophysiological properties of GABAA receptors and the expression of GABAAα1 and α2 subunits in cultured motor neurons obtained from a genetic model of amyotrophic lateral sclerosis (G93A) and compared them with transgenic wild‐type Cu,Zn superoxide dismutase and their corresponding non‐transgenic littermates (Control). In all tested motor neurons, the application of γ‐aminobutyric acid (GABA) (0.5–100 μm) evoked an inward current that was reversibly blocked by bicuculline (100 μm), thus indicating that it was mediated by the activation of GABAA receptors. Our results indicate that the current density at high GABA concentrations is similar in control, Cu,Zn superoxide dismutase and G93A motor neurons. However, the dose‐response curve significantly shifted toward lower concentration values in G93A motor neurons and the extent of desensitization also increased in these neurons. Finally, multiplex single‐cell real‐time polymerase chain reaction and immunofluorescence revealed that the amount of GABAAα1 subunit was significantly increased in G93A motor neurons, whereas the levels of α2 subunit were unchanged. These data show that the functionality and expression of GABAA receptors are altered in G93A motor neurons inducing a higher Cl− influx into the cell with a possible consequent neuronal excitotoxicity acceleration.
Glial responses, neuron death and lesion resolution after intracerebral hemorrhage in young vs. aged rats
Authors: Wasserman Jason K. , Yang Helen , Schlichter Lyanne C.
Published: October 2008

Intracerebral hemorrhage (ICH) usually affects older humans but almost no experimental studies have assessed aged animals. We address how aging alters inflammation, neuron death and lesion resolution after a hemorrhage in the rat striatum. In the normal aged brain, microglia displayed a ‘dystrophic’ phenotype, with shorter cellular processes and large gaps between adjacent cells, and there was more astrocyte reactivity. The ICH injury was monitored as hematoma volume and number of dying neurons at 1 and 3 days, and the volume of the residual lesion, ventricles and lost tissue at 28 days. Inflammation at 1 and 3 days was assessed from densities of microglia with resting vs. activated morphologies, or expressing the lysosomal marker ED1. Despite an initial delay in neuron death in aged animals, by 28 days, there was no difference in neuron density or volume of tissue lost. However, lesion resolution was impaired in aged animals and there was less compensatory ventricular expansion. At 1 day after ICH, there were fewer activated microglia/macrophages in the aged brain, but by 3 days there were more of these cells at the edge of the hematoma and in the surrounding parenchyma. In both age groups a glial limitans had developed by 3 days, but astrocyte reactivity and the spread of activated microglia/macrophages into the surrounding parenchyma was greater in the aged. These findings have important implications for efforts to reduce secondary injury after ICH and to develop anti‐inflammatory therapies to treat ICH in aged humans.
Colonic volvulus – an old problem with a new twist
Authors: Lehane C. W. , Gold D. M.
Published: October 2008

We present a case report involving an unusual type of volvulus. A 51‐year‐old man presented with an acute abdomen. He underwent emergency laparotomy at which we identified a volvulus involving his caecum to descending colon in continuity. We believe this to be first reported case of total colonic volvulus.
Hodgkin’s disease of appendix: report of a case
Authors: Umer M. A. , Date R. S. , Mellor S. , Nair B. , Ward J. B.
Published: October 2008

Background  A number of cases of non Hodgkin’s lymphoma of the appendix have been described, but Hodgkin’s lymphoma is extremely rare. To our knowledge there are only two reports up to 1966 and none since then.

Method  We report a case of a 65‐year‐old gentleman who was treated for suspected Crohn’s disease. He failed to respond to medical treatment and underwent right haemicolectomy. The resected segment of bowel demonstrated classical Hodgkin’s disease originating in the appendix. He recovered well from the operation and responded well to postoperative chemotherapy.

Conclusion  Hodgkin’s lymphoma of appendix is extremely rare. This case demonstrates the significance of repeated clinical evaluation of patients particularly in the absence of expected response to therapy.
The value of routine histopathological analysis in patients with fistula in‐ano
Authors: Wijekoon N. S. , Samarasekera D. N.
Published: October 2008

Objective  To determine the positive yield of routine histopathology in patients undergoing surgery for fistula in‐ano.

Method  Histopathology reports of all the patients who underwent surgery for fistulae‐in‐ano over a period of 36 months were reviewed.

Results  Analysis included 84 patients of which 73 (87%) were male subjects. The mean age was 39.4 years (range 11–68). Forty‐one (49%) had recurrent fistulae. Granulomatous diseases such as Crohn’s disease and tuberculosis (TB) were suspected in six patients. However, of the six patients, confirmation of the disease status was obtained only in three patients: stains for acid‐fast bacilli confirmed TB in two (2.4%) patients and colonoscopy and biopsy confirmed Crohn’s disease in one (1.2%) patient. All three patients had recurrent fistulae.

Conclusion  As the positive yield of routine histopathology is minimal, we do not recommend routine histopathology for fistula in‐ano, except for those presenting with recurrent fistulae and those with clinical suspicion of an underlying disease such as TB, HIV or Crohn’s disease.
Perioperative care in colorectal surgery: current practice patterns and opinions
Authors: Roig J. V. , García‐Fadrique A. , Redondo C. , Villalba F. L. , Salvador A. , García‐Armengol J.
Published: October 2008

Objective  Evidence regarding perioperative care in colorectal surgery has recently increased, leading to changes in classical clinical procedures that make the perioperative period safer and shorter. This survey aimed to evaluate the opinions of Spanish colorectal surgeons on the perioperative management of their patients.

Method  Emailed surveys submitted to the members of Spanish Coloproctological Associations.

Results  One hundred and thirty‐one (31.7%) of the 413 members participated in the study and responded thus: 21% use clinical pathways and 8% use fast track (FT); 36% use epidural analgesia in colonic surgery and 57% in rectal; 40% use warm air and 23% warm fluids to maintain intraoperative normothermia; 53% prescribe ≥ 3000 ml. of iv fluids on the first postoperative day and 6.2%≤ 2000 ml; 43% never use nasogastric tubes. Oral intake was initiated by 23.5% on the first day, and by 50% when peristalsis began, with an earlier tendency in laparoscopic surgery; 43% believed oral intake reduces ileus, but 12% considered it dangerous. Board accreditation and experience in Coloproctology were significantly associated with a lesser use of nasogastric tubes and earlier feeding. Sixty‐nine per cent considered FT reduces postoperative stay and 44% thought that it minimizes complications.

Conclusion  Spanish surgeons maintain a classical procedural policy, but show tendencies towards optimizing patients’ care.
The metabolic syndrome is related to albuminuria in Type 2 diabetes
Authors: Bianchi C. , Penno G. , Daniele G. , Russo E. , Giovannitti M. G. , Del Prato S. , Miccoli R.
Published: October 2008

Aims  To determine the relationships between metabolic syndrome (MetS), diabetic nephropathy (DN) and renal function in Type 2 diabetes.

Methods  In a clinic‐based cohort of 1314 Type 2 diabetic patients (58% male; age 62 ± 10 years), we analysed MetS, detected DN and estimated glomerular filtration rate (eGFR).

Results  Prevalence of both microalbuminuria and macroalbuminuria were higher in subjects with MetS than in those without. Prevalence of DN (microalbuminuria and macroalbuminuria) increased with the number of MetS components. eGFR was lower in subjects with MetS than in those without (87 ± 23 vs. 92 ± 20 ml/min per 1.73 m2; P < 0.001). The lowest eGFR values were found in those with four or more components of the MetS. Prevalence of low eGFR increased with the stage of DN and was affected by MetS only in normoalbuminuric patients. MetS was independently associated with DN, also after adjustment for confounders [odds ratio (OR) 2.82, confidence interval (CI) 1.93, 4.11] and the presence of low eGFR in the model (OR 2.74, CI 1.87, 4.01). Similarly, MetS was a predictor of low eGFR (OR 1.93, CI 1.11, 3.36), but after adjustment for DN, the association was lost. Finally, MetS per se was independently associated with DN, but not with low eGFR after adjustment for all of the individual components of the MetS.

Conclusions  This study suggests a close and independent association between MetS and renal impairment. However, it is unclear whether and to what extent treating MetS by an intensive multifactorial therapeutic approach will prevent or delay progression to renal failure.
Comparison of maternal ghrelin and leptin in healthy mothers and mothers with Type 1 diabetes
Authors: Kos K. , Syn W‐K. , Lewandowski K. C. , Bennett J. , Nwokolo C. U. , O’Hare J. P. , Randeva H.
Published: October 2008

Aims  Maternal leptin affects placental growth hormone (GH), whereas ghrelin, a natural ligand of the growth‐hormone‐secretagogue receptor, modulates GH action. Both hormones may affect fetal growth, and dysregulation in diabetes may lead to fetal growth disturbances. The aim was to investigate changes in maternal ghrelin during pregnancy with diabetes and to establish reference leptin levels.

Methods  Twelve healthy non‐diabetic (ND) and 12 pregnant women with Type 1 diabetes (T1DM) were recruited. Age and body mass index (BMI) [ND: age 29.9 ± 4.7 years (mean ± sd), BMI 25.2 ± 3.7 kg/m2; T1DM: age 31 ± 5.5 years, BMI 27 ± 3.1 kg/m2] were similar in the groups. HbA1c in T1DM was 6.2 ± 1.1% at 20 weeks, 6.3 ± 1.1% at 30 weeks’ gestation and 7.8 ± 2.1% postpartum. Fasting plasma ghrelin, total leptin, free leptin (FL) and soluble leptin receptor (sOB‐R) levels were measured at 20 and 30 weeks’ gestation and postpartum and determined by radioimmunoassay.

Results  All pregnancies resulted in full‐term singleton births with no differences in birth weight between groups [T1DM: 3.4 ± 0.56 kg (mean ± SE); ND: 3.6 ± 0.3 kg, P = NS]. Ghrelin levels were lower in T1DM when corrected for age and mothers’ weight (T1DM: 458 ± 36 pg/ml and 432.9 ± 26.6 pg/ml; ND: 562 ± 52 pg/ml and 515.8 ± 63 pg/ml at 20 and 30 weeks, respectively, P < 0.05). T1DM mothers had higher levels of sOB‐R and FL levels declined at 30 weeks’ gestation in T1DM (P = 0.04) but not in ND.

Conclusion  In a population of pregnant women with expected changes in leptin levels as previously reported, ghrelin levels were lower in T1DM pregnancies at 20 and 30 weeks. This may have implications for fetal development and requires further study in diabetes, particularly in pregnancies that result in macrosomia.
Mathematical Analysis of a Soccer Game. Part I: Individual and Collective Behaviors
Authors: Yue Zengyuan , Broich Holger , Seifriz Florian , Mester Joachim
Published: October 2008

Detailed time series analysis of a soccer match is given based on the detailed data of the 2D motions of all 22 players and of the ball for the match. The whole analysis includes two parts. In Part I, the individual and collective behaviors of the players of the two teams as well as the motion of the ball are presented as various time series. Geometrical centers, radii, expansion speeds, possession functions of the two teams are defined and calculated as functions of time. Major ranges of all players as well as of different groups of players (defenders, midfielders, forwards) of the two teams during the entire first half, the attacking phase of team A and the attacking phase of team B are calculated, respectively, showing the structures of the two teams during different phases. Distance coverage of each player and the mean distances covered by different groups of players (defenders, midfielders, forwards) during different phases are calculated. The time portions of possession of the ball by each team and the time portions of different phases are also calculated. In Part II, energy and spectral analysis and various correlations will be derived. The relation between various parameters and potential indicators will be discussed. The major purpose of the present study is to offer some general mathematical tools for the detailed analysis and to reveal some general features of soccer match when the detailed 2D data are available. The results would offer the raw materials for various potential indicators which may eventually be used in the coaching process to enhance the performance and in the prediction of the results of soccer matches.
Dyck Paths with Peak‐ and Valley‐Avoiding Sets
Authors: Liu Shu‐Chung , Ma Jun , Yeh Yeong‐Nan
Published: October 2008

In this paper, we focus on Dyck paths with peaks and valleys, avoiding an arbitrary set of heights. The generating functions of such types of Dyck paths can be represented by continued fractions. We also discuss a special case that requires all peak and valley heights to avoid congruence classes modulo k. We study the shift equivalence on sequences, which in turn induces an equivalence relation on avoiding sets.
Damping of Periodic Waves in Physically Significant Wave Systems
Authors: Ablowitz M. J. , Ablowitz S. A. , Antar N.
Published: October 2008

Damping of periodic waves in the classically important nonlinear wave systems—nonlinear Schrödinger, Korteweg–deVries (KdV), and modified KdV—is considered here. For small damping, asymptotic analysis is used to find an explicit equation that governs the temporal evolution of the solution. These results are then confirmed by direct numerical simulations. The undamped periodic solutions are given in terms of Jacobi elliptic functions. The damping structure is found as a function of the elliptic function modulus,m=m(t). The damping rate of the maximum amplitude is ascertained and is found to vary smoothly from the linear solution whenm= 0to soliton waves whenm= 1.
Regional distribution of tetrahydroisoquinoline derivatives in rodent, human, and parkinson’s disease brain
Authors: DeCuypere Michael , Lu Yan , Miller Duane D. , LeDoux Mark S.
Published: October 2008

Several members of the tetrahydroisoquinoline (TIQ) family of monoamine alkaloids can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death in Parkinson’s disease (PD). Using enantiomeric‐selective high‐performance liquid chromatography with electrochemical detection and liquid chromatography with tandem mass spectroscopy, the regional concentrations of several TIQ derivatives, including salsolinols, were determined in mouse, rat, normal human, and PD brain. TIQ derivatives were detected in all regions subjected to analysis. In general, salsolinols were present at higher concentrations than TIQ and its benzyl and methyl derivatives, especially in human brain. Moreover, salsolinols were concentrated in areas with increased dopamine synthesis and turnover such as the ventral midbrain and striatum, respectively. A possible consequence of nigrostriatal dopaminergic cell death, significantly lower levels of (R)salsolinol, (S)salsolinol, N‐methyl‐(R)salsolinol and N‐methyl‐(S)salsolinol were found in the caudate nuclei of PD in comparison with normal human brain. Our data support the hypothesis of endogenous synthesis of salsolinols and provide evidence for their accumulation in catecholaminergic neurons.
The guanine nucleotide exchange factor, C3G regulates differentiation and survival of human neuroblastoma cells
Authors: Radha Vegesna , Rajanna Ajumeera , Gupta Rajesh Kumar , Dayma Kunal , Raman Thiagarajan
Published: October 2008

Neuronal differentiation involving neurite growth is dependent on environmental cues which are relayed by signalling pathways to actin cytoskeletal remodelling. C3G, the exchange factor for Rap1, functions in pathways leading to actin reorganization and filopodia formation, processes required during neurite growth. In the present study, we have analyzed the function of C3G, in regulating neuronal cell survival and plasticity. Human neuroblastoma cells, IMR‐32 induced to differentiate by serum starvation or by treatment with nerve growth factor (NGF) or forskolin showed enhanced C3G protein levels. Transient over‐expression of C3G stimulated neurite growth and also increased responsiveness to NGF and serum deprivation induced differentiation. C3G‐induced neurite growth was dependent on both its catalytic and N‐terminal regulatory domains, and on the functions of Cdc42 and Rap1. Knockdown of C3G using small hairpin RNA inhibited forskolin and NGF‐induced morphological differentiation of IMR‐32 cells. Forskolin‐induced differentiation was dependent on catalytic activity of C3G. Forskolin and NGF treatment resulted in phosphorylation of C3G at Tyr504 predominantly in the Golgi. C3G expression induced the cell cycle inhibitor p21 and C3G knockdown enhanced cell death in response to serum starvation. These findings demonstrate a novel function for C3G in regulating survival and differentiation of human neuroblastoma cells.
Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia?
Authors: Scarr Elizabeth , Dean Brian
Published: October 2008

The high affinity of antipsychotic drugs for the dopamine D2 receptor focused attention onto the role of these receptors in the genesis of psychoses and the pathology of schizophrenia. However, psychotic symptoms are only one aspect of the complex symptom profile associated with schizophrenia. Therefore, research continues into other neurochemical systems and their potential roles in key features associated with schizophrenia. Modulating the cholinergic system in attempts to treat schizophrenia predates specific neurochemical hypotheses of the disorder. Cholinergic modulation has progressed from the use of coma therapy, through the use of anti‐cholinergic drugs to control side‐effects of older (typical) antipsychotic medications, to the development of drugs designed to specifically activate selected muscarinic receptors. This review presents data implicating a decrease in muscarinic receptors, particularly the M1 receptor, in the pathology of schizophrenia and explores the potential physiological consequences of such a change, drawing on data available from muscarinic receptor knockout mice as well as clinical and pre‐clinical pharmacology. The body of evidence presented suggests that deficits in muscarinic receptors are associated with some forms of schizophrenia and that targeting these receptors could prove to be of therapeutic benefit to patients with the disorder.
Fetal Alcohol Spectrum Disorders: An Overview of Interventions for Affected Individuals
Authors: Chandrasena Amali N. , Mukherjee Raja A. S. , Turk Jeremy
Published: October 2008

Whilst much has been written about understanding the diagnostic and underlying pathological processes related to prenatal alcohol exposure, far less has been directed at the management of affected individuals. We undertake a review of the literature focusing on a range of interventions including psychological, social, educational, pharmacological as well recent advances and directions. This paper is designed to give an overview on the management of this complex disorder.
The Paediatric Bipolar Hypothesis: The View from Australia and New Zealand
Authors: Parry Peter , Furber Gareth , Allison Stephen
Published: October 2008

Background:  The paediatric bipolar disorder (PBD) hypothesis arose in the USA and proposes childhood onset and high rates of prevalence.

Method:  Child and adolescent psychiatrists in Australia and New Zealand were surveyed about the PBD hypothesis.

Results:  Sixty percent responded (N = 199) and most (53%) reported never having diagnosed pre‐pubertal PBD and a further 29% estimated seeing ‘1 or 2’ cases. Most (83%) rated pre‐pubertal PBD as ‘very rare’, ‘rare’ or ‘not diagnosable’. Opinion varied as to whether PBD was over‐diagnosed (25%), appropriately diagnosed (42%), or under‐diagnosed (28%) in Australia and New Zealand, 5% were unsure. In contrast there was a consensus of views that PBD was over‐diagnosed in the USA (90%), whilst less felt it appropriately diagnosed (3%), or under‐diagnosed (1%) and 6% were unsure.

Conclusions:  The majority view was consistent with classical descriptions of bipolar disorder.
Development of a Scale to Assess the Attitudes of Paediatric Staff to Caring for Children with Medically Unexplained Symptoms: Implications for the Role of CAMHS in Paediatric Care
Authors: Glazebrook Cristine , Furness Penny , Tay Jasmine , Abbas Kirsty , Hollis Karmen Slaveska
Published: October 2008

Background:  Children with medically unexplained symptoms (MUS) represent a challenge for paediatricians and typically undergo extensive in‐patient investigations for symptoms such as abdominal pain. This can delay access to psychological services. This study aims to develop and evaluate a scale to assess the attitudes of paediatric staff to caring for children with MUS and to explore factors influencing those attitudes.

Method:  In this cross‐sectional survey, 118 health professionals at one UK hospital with experience of caring for children with MUS completed an attitude questionnaire developed for the study.

Results:  Factor analysis identified four factors that explained significant variance in staff perceptions of care: rewarding nature of care; demanding nature of care; parental influence; children’s need for skilled support. The combined subscales formed the MUS‐Q.

Conclusion:  Paediatric staff found caring for children with MUS difficult and would welcome more support from CAMHS. The MUS‐Q proved a reliable tool to evaluate staff attitudes.
Effects of the Glucocorticoid Antagonist, Mifepristone, on the Consequences of Withdrawal From Long Term Alcohol Consumption
Authors: Jacquot Catherine , Croft Adam P. , Prendergast Mark A. , Mulholland Patrick , Shaw Sidney G. , Little Hilary J.
Published: October 2008

Background: Studies were carried out to test the hypothesis that administration of a glucocorticoid Type II receptor antagonist, mifepristone (RU38486), just prior to withdrawal from chronic alcohol treatment, would prevent the consequences of the alcohol consumption and withdrawal in mice.

Materials and Methods: The effects of administration of a single intraperitoneal dose of mifepristone were examined on alcohol withdrawal hyperexcitability. Memory deficits during the abstinence phase were measured using repeat exposure to the elevated plus maze, the object recognition test, and the odor habituation/discrimination test. Neurotoxicity in the hippocampus and prefrontal cortex was examined using NeuN staining.

Results: Mifepristone reduced, though did not prevent, the behavioral hyperexcitability seen in TO strain mice during the acute phase of alcohol withdrawal (4 hours to 8 hours after cessation of alcohol consumption) following chronic alcohol treatment via liquid diet. There were no alterations in anxiety‐related behavior in these mice at 1 week into withdrawal, as measured using the elevated plus maze. However, changes in behavior during a second exposure to the elevated plus maze 1  week later were significantly reduced by the administration of mifepristone prior to withdrawal, indicating a reduction in the memory deficits caused by the chronic alcohol treatment and withdrawal. The object recognition test and the odor habituation and discrimination test were then used to measure memory deficits in more detail, at between 1 and 2 weeks after alcohol withdrawal in C57/BL10 strain mice given alcohol chronically via the drinking fluid. A single dose of mifepristone given at the time of alcohol withdrawal significantly reduced the memory deficits in both tests. NeuN staining showed no evidence of neuronal loss in either prefrontal cortex or hippocampus after withdrawal from chronic alcohol treatment.

Conclusions: The results suggest mifepristone may be of value in the treatment of alcoholics to reduce their cognitive deficits.
Neuropsychological Study of FASD in a Sample of American Indian Children: Processing Simple Versus Complex Information
Authors: Aragón Alfredo S. , Kalberg Wendy O. , Buckley David , Barela‐Scott Lindsey M. , Tabachnick Barbara G. , May Philip A.
Published: October 2008

Background:  Although a large body of literature exists on cognitive functioning in alcohol‐exposed children, it is unclear if there is a signature neuropsychological profile in children with Fetal Alcohol Spectrum Disorders (FASD). This study assesses cognitive functioning in children with FASD from several American Indian reservations in the Northern Plains States, and it applies a hierarchical model of simple versus complex information processing to further examine cognitive function. We hypothesized that complex tests would discriminate between children with FASD and culturally similar controls, while children with FASD would perform similar to controls on relatively simple tests.

Methods:  Our sample includes 32 control children and 24 children with a form of FASD [fetal alcohol syndrome (FAS) = 10, partial fetal alcohol syndrome (PFAS) = 14]. The test battery measures general cognitive ability, verbal fluency, executive functioning, memory, and fine‐motor skills.

Results:  Many of the neuropsychological tests produced results consistent with a hierarchical model of simple versus complex processing. The complexity of the tests was determined “a priori” based on the number of cognitive processes involved in them. Multidimensional scaling was used to statistically analyze the accuracy of classifying the neurocognitive tests into a simple versus complex dichotomy. Hierarchical logistic regression models were then used to define the contribution made by complex versus simple tests in predicting the significant differences between children with FASD and controls. Complex test items discriminated better than simple test items. The tests that conformed well to the model were the Verbal Fluency, Progressive Planning Test (PPT), the Lhermitte memory tasks, and the Grooved Pegboard Test (GPT). The FASD‐grouped children, when compared with controls, demonstrated impaired performance on letter fluency, while their performance was similar on category fluency. On the more complex PPT trials (problems 5 to 8), as well as the Lhermitte logical tasks, the FASD group performed the worst.

Conclusions:  The differential performance between children with FASD and controls was evident across various neuropsychological measures. The children with FASD performed significantly more poorly on the complex tasks than did the controls. The identification of a neurobehavioral profile in children with prenatal alcohol exposure will help clinicians identify and diagnose children with FASD.
S‐Adenosyl‐L‐Methionine Co‐administration Prevents the Ethanol‐Elicited Dissociation of Hepatic Mitochondrial Ribosomes in Male Rats
Authors: Sykora Peter , Kharbanda Kusum K. , Crumm Sara E. , Cahill Alan
Published: October 2008

Background:  Chronic ethanol feeding to male rats has been shown to result in decreased mitochondrial translation, depressed respiratory complex levels and mitochondrial respiration rates. In addition, ethanol consumption has been shown to result in an increased dissociation of mitoribosomes. S‐adenosyl‐L‐methionine (SAM) is required for the assembly and subsequent stability of mitoribosomes and is depleted during chronic ethanol feeding. The ability of dietary SAM co‐administration to prevent these ethanol‐elicited lesions was investigated.

Methods:  Male Sprague‐Dawley rats were fed a nutritionally adequate liquid diet with ethanol comprising 36% of the calories according to a pair‐fed design for 28 days. For some animals, SAM was supplemented in the diet at 200 mg/l. Liver mitochondria were prepared and mitoribosomes isolated. Respiration rates, ATP levels, respiratory complex levels, and the extent of mitoribosome dissociation were determined.

Results:  Twenty‐eight days of ethanol feeding were found to result in decreased SAM content, depressed respiration, and increased mitoribosome dissociation. No changes in mitochondrial protein content; levels of respiratory complexes I, III, and V; complex I activities; and ATP levels were detected. Co‐administration of SAM in the diet was found to prevent ethanol‐induced SAM depletion, respiration decreases and mitoribosome dissociation.

Conclusions:  Taken together, these findings suggest (1) that mitoribosome dissociation precedes respiratory complex depressions in alcoholic animals and (2) that dietary supplementation of SAM prevents some of the early mitochondrial lesions associated with chronic ethanol consumption.
Effects of Alcoholism Typology on Response to Naltrexone in the COMBINE Study
Authors: Bogenschutz Michael P. , Scott Tonigan J. , Pettinati Helen M.
Published: October 2008

Background:  This study investigated whether subgroups of alcohol‐dependent patients responded differently to naltrexone versus placebo in the NIAAA COMBINE study. In particular, the A versus B and the Early Onset versus Late Onset typologies were examined. Relative to Type A alcoholics, Type B alcoholics are characterized by greater severity, earlier onset, stronger family history, more childhood risk factors (e.g., conduct disorder), and greater frequency of comorbid psychiatric and substance use disorders.

Methods:  COMBINE study participants were categorized as Type A or Type B using k‐means cluster analysis and variables from 5 domains that have been shown to replicate the original Babor typology efficiently. Early Onset was defined as alcohol dependence beginning before age 25. For the planned analyses, the sample was reduced to the 618 participants receiving naltrexone alone or placebo, either with medical management (MM) alone or with MM plus the Combined Behavioral Intervention (CBI). The a priori primary outcome was percent heavy drinking days during treatment in the groups receiving MM without CBI.

Results:  Among those receiving MM without CBI, Type A alcoholics had better drinking outcomes with naltrexone than placebo, whereas medication condition did not influence outcomes significantly in the Type Bs. Age of onset was not significantly related to outcome. For those receiving CBI, no significant effects were found for either typology.

Conclusions:  In this sample, the beneficial effects of opioid antagonism were limited to Type A alcoholics receiving treatment in a MM model. Future studies should investigate the relationship between clinically relevant genotypes, phenotypes such as typologies, and treatment response. More work is also needed to develop practical algorithms for phenotypic assignment.
A Comparison of How Generalists and Fellowship‐Trained Geriatricians Provide “Geriatric” Care
Authors: Phelan Elizabeth A. , Genshaft Scott , Williams Barbara , LoGerfo James P. , Wagner Edward H.
Published: October 2008

OBJECTIVES: To determine whether outpatient care provided to older patients by fellowship‐trained geriatricians is distinguishable from that provided by generalists.

DESIGN: Observational study.

SETTING: Three primary care clinics of an academic medical center.

PARTICIPANTS: Random sample of 140 adults aged 65 and older receiving primary care at one of the clinics.

MEASUREMENTS: A medical chart review involving records of 69 patients receiving primary care from a fellowship‐trained geriatrician and 71 patients receiving primary care from a generalist (general internal medicine or family practice) was conducted; information pertaining to two practice behaviors relevant to the care of older adults—avoidance of inappropriate prescribing and proactive assessments for geriatric syndromes—was abstracted.

RESULTS: Geriatricians scored 17.6 out of a possible 24 points, on average; generalists scored 14.2 (P<.001). Geriatricians scored higher than generalists on prescribing and geriatric syndrome assessments. In a linear regression model adjusting for patient age and number of comorbidities and clustering according to provider, provider specialty was strongly associated with overall score (β coefficient for specialty=6.75, P<.001; 95% confidence interval=4.57–8.94).

CONCLUSION: The practice style of fellowship‐trained geriatricians caring for older adults appears to differ from that of generalists with regard to prescribing behavior and assessment for geriatric syndromes.
Correlation of Left Atrial Diameter by Echocardiography and Left Atrial Volume by Computed Tomography
Authors: HOF IRENE , ARBAB‐ZADEH ARMIN , SCHERR DANIEL , CHILUKURI KARUNA , DALAL DARSHAN , ABRAHAM THEODORE , LIMA JOAO , CALKINS HUGH
Published: October 2008

Introduction:
For patients undergoing catheter ablation of atrial fibrillation (AF), left atrial size is a predictor of recurrence of AF during follow‐up. For this reason, major clinical trials have used a left atrial diameter (LAD) of more than 5.0 or 5.5 cm, assessed by echocardiography, as an exclusion criterion for patients deemed candidates for ablation of AF. However, whether LAD accurately reflects true left atrial size has not been systematically investigated. Therefore, the purpose of this study was to test the hypothesis that LAD, measured by echocardiography, accurately correlates to left atrial volume measured by computed tomography (CT).

Methods and Results:
We included 50 patients (mean age 56 ± 12 years, five female) with symptomatic AF (40% paroxysmal, 60% persistent), referred for catheter ablation. In each patient, transthoracic echocardiography was performed. Additionally, all patients underwent CT using a 64‐slice CT scanner. Left atrial volume was calculated by manually tracing left atrial area on each CT cross‐sectional image. Patients had a mean LAD measured by echocardiography of 4.5 ± 0.7 cm, ranging from 2.9 to 5.7 cm. Left atrial volume measured by CT ranged from 67 mL to 270 mL with a mean value of 146 ± 49 mL. A poor correlation was noted between LAD and left atrial volume, r = 0.49 (P < 0.001).

Conclusion:
LAD measured by echocardiography correlates poorly with left atrial volume measured by CT in patients with AF. As a result, selecting patients with AF for treatment with catheter ablation should not be based on an echocardiographic‐derived LAD alone.