bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrient Limitation in Macroalgae (Ulva and Enteromorpha) from the Rías Baixas (NW Spain)
Authors: Villares Ruben , Carballeira Alejo
Published: September 2004

Abstract.  Photosynthesis and growth rates in samples of two green seaweeds (Ulva and Enteromorpha) were monitored in the laboratory. The macroalgae were collected every 15 days from four coastal embayments in Galicia (NW Spain). Ulva samples were found to be nutritionally limited, particularly in summer. The physiological activity of Enteromorpha did not appear to be as affected by nutrient scarcity, although it may have suffered from phosphorus limitation. The subsistence quotas, critical concentrations and storage capacity for N and P in Ulva were comparable to those obtained by other investigators in similar studies. The trace metals analysed apparently did not negatively affect the macroalgae at the measured concentrations; one explanation is that many of these metals function as essential micronutrients. The complex physiological interactions between metals and nutrients, however, may complicate interpretation of the results.
Development of Adolescents' Self‐Perceptions, Values, and Task Perceptions According to Gender and Domain in 7th‐ through 11th‐Grade Australian Students
Authors: Watt Helen M. G.
Published: September 2004

Latent growth models estimated developmental trajectories for adolescents' math and English self‐perceptions (perceived talent, success expectancies), values (intrinsic, utility) and task perceptions (task difficulty, effort required). A longitudinal cohort‐sequential study included 1,323 participants spanning Grades 7 to 11, with Occasion 1 mean ages 13.19, 12.36, and 14.41, respectively, for Cohorts 1, 2, and 3. Self‐perceptions and values declined through adolescence, and ratings about difficulty and effort required increased. Gender differences favored boys for math and girls for English, with little evidence for gender intensification or gender convergence hypotheses. Explanations reference socialization and social‐cognitive developmental theories and features of the curricula, with domain‐specific patterns implying domain‐specific explanations. Existing research is extended by modeling a broadened set of social‐cognitive constructs within the Australian context.
GENOPHAR: a randomized study of plasma drug measurements in association with genotypic resistance testing and expert advice to optimize therapy in patients failing antiretroviral therapy*
Authors: Bossi P , Peytavin G , Ait‐Mohand H , Delaugerre C , Ktorza N , Paris L , Bonmarchand M , Cacace R , David D‐J , Simon A , Lamotte C , Marcelin A‐G , Calvez V , Bricaire F , Costagliola D , Katlama C
Published: September 2004

Objectives

To evaluate the benefits of therapeutic drug monitoring (TDM) in association with genotypic resistance testing and expert advice to optimize therapy in multiexperienced patients infected with HIV‐1.

Methods

Patients with a viral load>1000 HIV‐1 RNA copies/mL and an unchanged antiretroviral therapy regimen over the last 3 months were randomized into two groups: a genotypic group (G) and a geno‐pharmacological group (GP). Treatment was selected by an expert committee according to genotypic resistance testing (the G and GP groups) and TDM (the GP group) at week 4. Treatment could be modified at each visit according to toxicity, poor virological response and TDM. Results of TDM were withheld from the G group until week 12. The primary endpoint of the study was the percentage of patients with viral load<200 copies/mL at week 12.

Results

A total of 134 patients were randomized in the study, with 67 in each group, and included in the intent‐to‐treat (ITT) analysis. At baseline, median values were as follows: viral load (log10 copies/mL): G=4.1, GP=4.0; CD4 cell count (cells/μL): G=292, GP=294; and number of prior drugs: G=7, GP=8. The median number of resistance mutations was five in the G group [nucleoside reverse transcriptase inhibitors (NRTIs)=three; non‐nucleoside reverse transcriptase inhibitors (NNRTIs)=one; protease inhibitors (PI)=one] and seven in the GP group (NRTI=four; NNRTI=two; PI=one). At week 8, treatment was adjusted according to the TDM in 13 of the 67 patients in the GP group (19%). By ITT missing equal failure analysis at week 12, and after only one intervention according to plasma concentration results, a viral load<200 copies/mL was achieved in 30 of the 67 patients (45%) in the G group and in 29 of the 67 patients (43%) in the GP group (not significant). In the multivariate analysis, only prior exposure to at least two PIs at baseline gave a poor response to subsequent antiretroviral therapy. At week 24, a viral load<200 copies/mL was achieved in 35 of the 67 patients (52%) in the G group and in 40 of the 67 patients (60%) in the GP group.

Conclusions

A statistically significant benefit of using TDM was not found in this short‐term study where patients appeared to be adherent. However, combining genotypic resistance testing with the use of an expert committee to monitor subsequent therapy individually in patients with multiple resistance mutations was associated with high antiviral efficacy.
A significant proportion of HIV‐infected patients admitted to hospital have immunosuppression as a result of failure of highly active antiretroviral therapy
Authors: Manavi K , McMillan A
Published: September 2004

Objectives

To investigate the immunological and virological features of patients on highly active antiretroviral therapy (HAART) admitted to a tertiary centre.

Methods

A retrospective study was carried out on HIV‐infected patients on HAART admitted to the Regional Infectious Disease Unit in Edinburgh between June 2002 and July 2003.

Results

A total of 125 patients who had been on HAART for at least 6 months were admitted during the study period. The frequencies of hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection were 52% (78 of 150 patients) and 48% (72 of 150 patients), respectively (P>0.05 for comparison of frequencies of hepatitis B and C). Of patients who had been on HAART for atleast 6 months, 50% (63 of 125 patients) were immuno‐suppressed and had significantly higher bed‐days 6 (3–12) compared with those with CD4>200 cells/μL (P<0.002). Amongst immuno‐suppressed patients, 38% (24 of 63) had undetectable viral load after at least 6 months of therapy. Those patients were mostly (67%) intravenous drug users and had a significantly higher median age (43 years; range 38–47 years) than other patients (P<0.001).

Conclusions

Earlier start of HAART and addition of interleukin (IL)‐2 to the treatment regimens of patients at risk of slow CD4 T‐cell count recovery may reduce the duration of their subsequent hospital admissions.
New international classification of migraine with aura (ICHD‐2) applied to 362 migraine patients
Authors: Eriksen M. K. , Thomsen L. L. , Olesen J.
Published: September 2004

The International Classification of Headache Disorders 2nd edition (ICHD‐2) subdivides migraine with aura (MA) differently from the ICHD‐1 and includes new diagnostic criteria. The aim of the present study was to evaluate how the new classification works in practice and in comparison with the ICHD‐1. The patients were recruited from a screen of the Danish National Patient Registry and from Danish neurologists. We included 362 patients diagnosed with MA according to the ICHD‐1 in a validated semistructured physician‐conducted interview. According to the ICHD‐2, 89% (322 of 362) had MA and 11% (40 of 362) had probable MA. The MA patients had one or more ICHD‐2 subtype of MA: 54% (173 of 322) had typical aura with migraine headache (MA‐MH), 40% (129 of 322) had typical aura with non‐migraine headache (MA‐NMH), 37% (120 of 322) had aura without headache (MA‐WOH), and 7% (26 of 322) had basilar‐type migraine (MA‐B). Of patients with MA‐MH 34% (59 of 173) had co‐occurrence of MA‐WOH, 9% (16 of 173) had co‐occurrence of MA‐B and 5% (8 of 173) had co‐occurrence of both MA‐WOH and MA‐B. Of patients with MA‐NMH 27% (35 of 129) had co‐occurrence of MA‐WOH. Only 6% (18 of 322) of the MA patients had exclusively MA‐WOH and <1% (2 of 322) had exclusively MA‐B. Patients with MA‐MH had an earlier age at onset (P = 0.044), an increased lifetime number of MA attacks (P = 0.054) and a higher co‐occurrence of migraine without aura (P = 0.002) than patients with MA‐NMH. Patients with MA‐B tended to have an earlier age at onset and more severe attacks and patients with MA‐WOH had a higher age at onset and less severe attacks than patients with MA‐MH. The variations between ICHD‐2 subtypes of MA indicate that patients with similar subtype of MA share phenotype and very likely have similar underlying aetiology.
Estimation of Antiphospholipid Antibodies in a Prospective Longitudinal Study of Children with Migraine
Authors: Avcin T , Markelj G , Niksic V , Rener-Primec Z , Cucnik S , Zupancic M , Rozman B , Neubauer D
Published: September 2004

The aim of this study was to determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in children with migraine. The values of anti-cardiolipin (aCL) and antiβ2 glycoprotein I (antiβ2GPI) antibodies were assayed by an ELISA method in 52 children with migraine and 22 children with tension-type headache. The control group consisted of 61 apparently healthy children at regular preventive visits. Two monoclonal β2GPI dependent aCL (HCAL and EY2C9) were used as calibrators. Lupus anticoagulant (LA) was determined by a modified dilute Russell viper venom time test. Persistently positive aPL were observed during the follow-up in 16.3% of children with migraine (9.3% for aCL, 7.0% for antiβ2GPI and 0% for LA) and in 16.7% of children with tension-type headache (11.1% for aCL, 5.6% for antiβ2GPI and 0% for LA). The prevalence of aPL did not differ significantly between patient groups and healthy children. The prevalence of aPL does not appear to be increased in an unselected group of children with migraine, however, the possible role of aPL in individual cases of paediatric migraine can not be excluded.
Botulinum Toxin A in the Prophylactic Treatment of Migraine – A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Evers S , Vollmer-Haase J , Schwaag S , Rahmann A , Husstedt I-W , Frese A
Published: September 2004

Botulinum toxin A has been suggested to be effective in the prophylactic treatment of migraine. However, only very few randomized, double-blind, placebo-controlled studies are available. We designed such a study with a specific focus on different injection sites. Sixty patients with a migraine according to the criteria of the International Headache Society were randomly assigned to receive either placebo in the frontal and neck muscles, or to receive 16 U botulinum toxin A in the frontal muscles and placebo in the neck muscles, or to receive in total 100 U botulinum toxin A in the frontal and neck muscles. The observation period was 3 months. In both treatment groups, 30% of patients showed a reduction of migraine frequency in month 3 by at least 50% compared with baseline, in the placebo group 25% of the patients showed such a reduction ( P = 0.921). There were no significant differences between the three study groups with respect to reduction of migraine frequency, number of days with migraine, and the number of total single doses to treat a migraine attack. In the post hoc analysis, the reduction of all accompanying symptoms was significantly higher in the 16 U treatment group compared with the placebo group. In the 100 U treatment group significantly more adverse events occurred compared with the placebo group. All adverse events were mild and transient. Our study did not show any efficacy of botulinum toxin A in the prophylactic treatment of migraine. Only accompanying symptoms were significantly reduced in the 16 U but not in the 100 U treatment group. Future studies should focus on the efficacy of botulinum toxin A in specific subgroups of patients, on the efficacy of repetitive injections, and on other injection sites.
Development of a Patient-Based Grading Scale for PedMIDAS
Authors: Hershey AD , Powers SW , Vockell A-LB , LeCates SL , Segers A , Kabbouche MA
Published: September 2004

The objective was to develop and validate a patient-based grading scale for PedMIDAS. PedMIDAS was administered to 329 children, who rated their overall disability based on the adult MIDAS grades. This patient-based rating and PedMIDAS scores were compared to develop the grading scale. Headache disability was rated little to none, 49.5%; mild, 26.7%; moderate, 15.8%; and severe, 7.9%, with PedMIDAS raw scores of 4.9 ± 6.3, 17.8 ± 14.9, 40.6 ± 34.2, and 91.4 ± 69.8. Convergence of these results yielded an empirically derived grading system: Grade I, 0-10; II, 11-30; III, 31-50 and IV, > 50. Higher grades corresponded to an increased need for prophylactic treatment. A patient-based grading scale further increases the utility of PedMIDAS in assessing migraine disability in children, so that it can be widely used in routine clinical evaluation and management.
Chronic Daily Headache in Childhood and Adolescence: Clinical Aspects and a 4-Year Follow-up
Authors: Galli F , Patron L , Russo PM , Bruni O , Strambi LF , Guidetti V
Published: September 2004

Chronic daily headache (CDH) represents a challenge in clinical practice and the scientific field. CDH with onset in children and adolescents represent a matchless opportunity to understand mechanisms involved in adult CDH. The aim of this study was to evaluate the diagnosis, prognosis and psychiatric co-morbidity of CDH with young onset in the young. Fifty-nine CDH patients has been followed from 1997 to 2001 in our department. Headache and psychiatric diagnoses were made on the basis of the international system of classification (International Headache Society, 1988; DSM-IV). X2test and multinomial logistic regressions were applied to analyse factors predicting outcome. The current diagnostic system allows a diagnosis in 80% of CDH patients, even if age-related characteristics have been evidenced. Psychiatric disorders are notable in CDH (about 64% of patients) and predict (mainly anxiety) a poorer outcome. Surprisingly, analgesic overuse is not involved in the chronicization process. Diagnosis of CDH needs further study. Psychiatric disorders predict a worse outcome and greater account should be taken of them in treatment planning.
Trigeminal Autonomic Cephalgias and Variants: Clinical Profile in Indian Patients
Authors: Chakravarty A , Mukherjee A , Roy D
Published: September 2004

The present study summarizes the authors' experience of the clinical profile of short-lasting trigeminal autonomic cephalgias (TAC) in Indian patients. Over a period of 17 years a total of 41 cases of episodic cluster headache, seven cases of chronic cluster headache, six cases of variant cluster headache, three cases of paroxysomal hemicrania, and a single case of SUNCT syndrome were encountered. TACs appear to be rare in Indian patients and cluster headache seems to be exclusively a disease of men. The present report is to the best of our knowledge the first of its kind to be reported from India.
Headache Profiles in Patients with a Dilatated Cyst of the Cavum Septi Pellucidi
Authors: Wang K-C , Fuh J-L , Lirng J-F , Huang W-C , Wang S-J
Published: September 2004

The dilatated cyst of the cavum septi pellucidi (CSP) is rare and may be associated with headaches. We reviewed the computerized database of 54 000 patients' computed tomography or magnetic resonance images and found 22 cases (0.04%) involving a dilatated cyst of the CSP. Sixteen patients had a chief complaint of headache, which was classified as acute episodic headache (type I, n = 7, 43.7%), chronic daily headache (CDH) with acute onset (type II, n = 5, 31.3%), or CDH with insidious onset (type III, n = 4, 25%). Acute Valsalva-induced headaches were common with type I (85%) or II (100%); 70% of these responded to indomethacin. At follow-up, patients with type I headache had the highest remission rate (71%), and type III patients the lowest (0%). Dilatated cysts of the CSP should be considered a cause of acute Valsalva-induced headache or new daily persistent headache, and may respond to indomethacin. A protracted course (≥ 3 months) indicates a worse outcome.
Validation of a Migraine Screening Questionnaire in a Colombian University Population
Authors: Rueda-Sánchez M , Díaz-Martínez LA
Published: September 2004

In studies of migraine prevalence, it is important to be aware of the discriminative capacity of the test used. We set out to validate a Spanish translation of Michel's Standardized Migraine Diagnosis Questionnaire. The questionnaire was applied on all active students of the School of Psychology of the Universidad Autónoma de Bucaramanga, Colombia. A neurologist interviewed a random sample to substantiate the diagnosis of migraine. Cronbach's α was calculated and factors analysis was made in order to estimate internal consistency, test-retest to find reproducibility, and ROC curve and diagnostic indicators were calculated to estimate the criteria validity. Of 357 students that answered the questionnaire, 188 (52.7%) were selected at random to attend an appointment with a neurologist, but only 170 had this interview. Cronbach's α on these 357 questionnaires is 0.7497. All the questions on the questionnaire represented two main factors. This test had sensitivity in 37.9% [95% confidence interval (CI) 25.8, 51.7], specificity in 99.1% (95% CI 94.4, 100), positive predictive value in 95.7% (95% CI 76.0, 99.8), and negative predictive value in 75.5% (95% CI 67.6, 82.1) for 17 or more points. The area below ROC curve is 0.8529 (95% CI 0.8035, 0.9217). Among 84 students who took the questionnaire a second time, the average score on the first survey was 12.33 ± 7.46 points, while the average score on the second take was 11.26 ± 7.85 ( P = 0.069). Agreement for migraine is 83.3% (95% CI 73.6, 90.6; Cohen's κ = 0.6650 ± 0.1061). The Spanish translation of Michel's Questionnaire is easy to answer and has good internal consistency, but its reproducibility and sensibility are modest; however, the ROC curve is acceptable to discriminate migraine patients from normal subjects.
In vivo regulation of dopamine and noradrenaline release by alpha2A‐adrenoceptors in the mouse nucleus accumbens
Authors: Ihalainen Jouni A. , Tanila Heikki
Published: September 2004

The present study investigated the role of alpha2A‐adrenoceptor (α2A‐AR) subtype in the regulation of noradrenaline (NA) and dopamine (DA) release in the nucleus accumbens (NAc). The effect of locally infused and systemically injected α2‐AR agonist, dexmedetomidine (DMT), and α2‐AR antagonist, atipamezole, on NA and DA release was investigated in α2A‐AR knockout and control mice by using in vivo microdialysis. In addition, we compared the drug effects on DA and NA release in the NAc to their effect on locomotor activity. Baseline NA and DA concentrations did not differ between genotypes. Local infusion of DMT decreased, in a concentration‐dependent manner, NA, but not DA, levels in the control mice. However, systemic injection of DMT decreased both NA and DA levels in the control mice. In both cases DMT had no effects on transmitter release in α2A‐AR knockout mice. Our results suggest that α2‐ARs regulate the release of NA, but not DA, at the terminal level in the NAc. However, α2‐ARs regulate DA release in the NAc indirectly by their effect on DA neurones in the ventral tegmental area via an unknown mechanism. In both cases the regulation is mediated by α2A‐adrenoceptor subtype. Also the modulation of locomotor activity by α2‐AR agonist and antagonist seems to be mediated via α2A‐adrenoceptors.
Dicyclohexylphthalate causes hyperactivity in the rat concomitantly with impairment of tyrosine hydroxylase immunoreactivity
Authors: Ishido Masami , Masuo Yoshinori , Sayato‐Suzuki Junko , Oka Syuichi , Niki Etsuo , Morita Masatoshi
Published: September 2004

Endocrine disruptors possibly exert effects on neuronal functions leading, in particular, to behavioural alterations. In this study, we examined the effects of dicyclohexylphthalate (DCHP), an endocrine disruptor, on rat behavioural and cellular responses. Single intracisternal administration of DCHP (0.87–87 nmol) into 5‐day‐old male Wistar rats caused significant hyperactivity at 4–5 weeks of age. It was about 1.4‐fold more active in the nocturnal phase after administration of 87 nmol of DCHP than control rats (p < 0.001). The response had a tendency to be dose‐dependent. Based on DNA macoarray analyses, DCHP down‐regulated the levels of gene expression of the dopamine D4 receptor at 4 weeks old in both the midbrain and the striatum, and the dopamine transporter in the midbrain at 8 weeks old 1.7‐ to 2‐fold. The gene expression of several subtypes of glutamate receptors was facilitated in the striatum at 4 weeks old and in the midbrain at 8 weeks old. Some normalization and/or compensatory changes seemed to occur in gene expression of GABA or glycine transmission. Furthermore, DCHP abolished immunoreactivity of tyrosine hydroxylase in the substantia nigra at 8 weeks of age, where TUNEL‐positive cells were seen. We conclude that DCHP affected the developing rat brain, resulting in hyperactivity, probably as a result of degeneration of mesencephalic tyrosine hydroxylase rather than alteration of the level of gene expression.
Biochemical characterization and immunohistochemical localization of urotensin II in the human brainstem and spinal cord
Authors: Chartrel Nicolas , Leprince Jérôme , Dujardin Cynthia , Chatenet David , Tollemer Hélène , Baroncini Marc , Balment Richard J. , Beauvillain Jean‐Claude , Vaudry Hubert
Published: September 2004

The human urotensin II (UII) precursor encompasses several potential cleavage sites and thus, processing of pro‐UII may generate various forms of mature UII including the peptides of 11 (UII11), 16 (UII16) and 19 (UII19) residues. Until now, the native form of human UII had not been characterized. Here, we show that the major UII peptide occurring in the human spinal cord corresponds to UII11. In contrast, neither the UII16 nor the UII19 forms could be detected. In 50% of the brainstem and in all the spinal cord extracts analysed, a second minor UII‐immunoreactive peptide was resolved. Immunohistochemical labelling of the cervical segment of the human spinal cord revealed that the UII‐immunoreactive material was confined to a subset of ventral horn motoneurones. These data provide the first evidence that in the human, the UII precursor, expressed in motoneurones, is processed at the tribasic KKR93 cleavage site to generate a mature form of UII of 11 amino acids. The absence of N‐terminally elongated forms of UII of 16 and 19 residues indicates that pro‐UII is not cleaved at the R85 or K88 monobasic sites. Finally, the minor UII‐immunoreactive peptide detected in several tissue extracts might correspond to an extended form of UII resulting from the processing of the UII precursor at the basic RK50 or RK66 doublets.
The 5‐HT2A receptor antagonist M100,907 prevents extracellular glutamate rising in response to NMDA receptor blockade in the mPFC
Authors: Ceglia Ilaria , Carli Mirjana , Baviera Marta , Renoldi Giuliano , Calcagno Eleonora , Invernizzi Roberto W.
Published: September 2004

We recently found that intracortical injection of the selective and competitive N‐methyl‐d‐aspartate (NMDA) receptor antagonist 3‐(R)‐2‐carboxypiperazin‐4‐propyl‐1‐phosphonic acid (CPP) impaired attentional performance in rats and blockade of 5‐hydroxytryptamine (5‐HT)2A receptors antagonized this effect. Here, we used the microdialysis technique in conscious rats to study the effect of CPP on extracellular glutamate (GLU) in the medial prefrontal cortex (mPFC) and the regulation of this effect by 5‐HT2A receptors. Intraperitoneal injection of 20 mg/kg CPP increased extracellular GLU in the mPFC (201% of basal levels) but had no effect on 5‐HT. Intracortical infusion of 100 µm CPP increased extracellular GLU (230% of basal values) and 5‐HT (150% of basal values) in the mPFC, whereas 30 µm had no significant effect. The effect of 100 µm CPP on extracellular GLU was abolished by tetrodotoxin, suggesting that neuronal activity is required. Subcutaneous injection of 40 µg/kg M100,907 completely antagonized the effect of 100 µm cpp on extracellular GLU, whereas 10 µg/kg caused only partial attenuation. Likewise, intracortical infusion of 0.1 µm M100,907 completely reversed the increase of extracellular GLU induced by CPP. These findings show that blockade of NMDA receptors in the mPFC is sufficient to increase extracellular GLU locally. The increase of cortical extracellular GLU may contribute to CPP‐induced cognitive deficits and blockade of 5‐HT2A receptors may provide a molecular mechanism for reversing these deficits caused by dysfunctional glutamatergic transmission in the mPFC.
Ubiquitin‐proteasome‐mediated CREB repressor degradation during induction of long‐term facilitation
Authors: Upadhya Sudarshan C. , Smith Thuy K. , Hegde Ashok N.
Published: September 2004

Long‐term facilitation in Aplysia and other forms of long‐term memory in invertebrates and vertebrates require the gene expression cascade induced by cAMP‐responsive element binding protein (CREB). Normally, gene expression by CREB is inhibited by repressors. The molecular mechanisms by which the repression is relieved are not understood. Our results show that Aplysia CREB repressor is a substrate for degradation by the ubiquitin‐proteasome pathway. Treatment with the facilitatory neurotransmitter 5‐hydroxy tryptamine (5‐HT) leads to CREB repressor degradation in vivo and the degradation can be blocked by a specific proteasome inhibitor. Our biochemical studies show that attachment of ubiquitin molecules marks the CREB repressor for degradation by the proteasome. Protein kinase C (PKC) stimulates ubiquitination and degradation of the CREB repressor. Our results suggest that proteolytic removal of the CREB repressor is a potential mechanism for controlling gene expression by CREB. Without stimulation, gene expression is suppressed by the CREB repressor. Upon stimulation with 5‐HT, PKC is activated, causing enhancement in ubiquitination and degradation of the CREB repressor. Thus, regulation of proteolysis of the CREB repressor by PKC might be critical in determining whether or not CREB‐mediated gene expression goes forward during induction of long‐term facilitation.
Protein processing and releases of neuregulin‐1 are regulated in an activity‐dependent manner
Authors: Ozaki Miwako , Itoh Kouich , Miyakawa Yukie , Kishida Haruo , Hashikawa Tsutomu
Published: September 2004

Identification of the key molecules that bridge presynaptic neuronal events and long‐term modification of the postsynaptic process is an important challenge which will have to be met in order to further our understanding of the mechanisms for learning and memory. This study is focused on neuregulin‐1 (NRG‐1), a neurotrophic factor, that is known to regulate the development of various tissues and/or the life/death of cells through activation of the ErbB family receptor tyrosine kinases. It was discovered that the soluble form of NRG‐1 (sNRG‐1) is produced from the transmembrane form of NRG through proteolytic cleavage during electrical stimulation of either cultured cerebellar granule cells (GCs) or pontine nucleus neurons (PNs) that are presynaptic to GCs. sNRG‐1 was assayed by measuring the phosphorylation of both the ErbB receptors and cyclic AMP‐responsive element‐binding protein (CREB), and by means of antibodies to sNRG‐1. The cleavage and release of NRG‐1 depended on the frequency of electrical stimulation; the peak effect was at 50 Hz in both GCs and PNs. Activation of protein kinase C (PKC) mimicked this effect. The culture apparatus provided along with the mass‐electrical stimulation that was employed proved to be a powerful tool for combining neuronal electrical events and chemical events. We conclude from the results that, in mossy fibre (PN axon)‐GC synapses, electrical activity controls the proteolytic processing of NRG‐1 in a frequency‐dependent fashion and involves PKC. Furthermore, cleaved sNRG‐1 plays an important functional role in regulating transmission across these synapses.
Novel tetranucleotide microsatellite markers from the Del Norte salamander (Plethodon elongatus) with application to its sister species the Siskiyou Mountain salamander (P. stormi)
Authors: DEGROSS DOUGLAS J. , MEAD LOUISE S. , ARNOLD STEVAN J.
Published: September 2004

Eleven tetranucleotide microsatellite loci were developed for the Del Norte salamander (Plethodon elongatus). The loci were variably polymorphic, ranging from two to 20 alleles per locus, with expected heterozygosities ranging from 0.07 to 0.86. The loci also amplified in a congener, the Siskiyou Mountain salamander (P. stormi). The microsatellite loci will be used to assess the utility of highly polymorphic markers to assay within‐ and between‐species differentiation between these two closely related species.
The Declaration of Rome 2003 – With Regard to the Promotion of Interest and Services for People with Intellectual Disabilities with Mental Health Needs
Authors: Seidel Michael
Published: September 2004

Abstract  The European Association for Mental Health in Mental Retardation (EAMHM) at its 4th European Congress in Rome, Italy, in September 2003, adopted the Declaration of Rome 2003, a policy statement designed to help promote greater awareness of the mental health aspects and needs of people with intellectual disabilities (ID). The statement accedes that all persons with ID have a right to the best available mental health care that is part of a nation's health and social care system. The Declaration is targeted toward public policy makers, administrators, politicians, professionals, researchers, and relatives or friends of people with ID with the goal of promoting and promoting increased access and more equitable provision of mental health services to people with ID.
Necrotising fasciitis: a new management algorithm based on clinical classification
Authors: Carter Paul S , Banwell Paul E
Published: September 2004

Necrotising fasciitis is a rare infection of the subcutaneous tissues. If untreated, it is invariably fatal, and thus a high index of suspicion for the diagnosis is required. The disease's manifestation can range from a fulminant presentation to a subtle and insidious development. The priority in every case is to proceed to radical surgical debridement. On review of the literature and based on our clinical experience, we propose a new classification based on clinical presentation and suggest an algorithm to facilitate the management of this devastating condition. Increasing awareness should be given to the management of the large wounds resulting from the surgical debridement of necrotising fasciitis.
H1 but not H2 histamine receptor activation contributes to the rise in skin blood flow during whole body heating in humans
Authors: Wong Brett J. , Wilkins Brad W. , Minson Christopher T.
Published: September 2004

Recent evidence suggests a role for vasoactive intestinal polypeptide (VIP) in active vasodilatation and it has been shown that VIP‐mediated vasodilatation includes a nitric oxide (NO) and histamine component. Thus, the purpose of this study was to determine the role of H1 and H2 histamine receptors and to examine a potential interaction between NO and histamine receptors in cutaneous active vasodilatation. Eleven subjects were instrumented with four microdialysis fibres. Site 1 served as a control and site 2 was perfused with l‐NAME to inhibit nitric oxide synthase. Site 3 was perfused with either the H1 antagonist pyrilamine maleate or the H2 antagonist cimetidine. Site 4 was perfused with l‐NAME plus pyrilamine maleate or l‐NAME plus cimetidine. Laser‐Doppler flowmetry (LDF) was used as an index of skin blood flow and cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure and normalized to maximal vasodilatation achieved via 28 mm sodium nitroprusside infusion. During whole body heating, subjects' sublingual temperature increased a minimum of 0.8°C. In the H1 antagonist studies, CVC in l‐NAME, pyrilamine, and combined l‐NAME plus pyrilamine sites was significantly reduced compared with control (P < 0.001). The l‐NAME and combined l‐NAME plus pyrilamine sites were significantly reduced compared with pyrilamine only sites (P < 0.05) but no significant differences were observed between sites. In the H2 receptor antagonist studies, CVC in control sites was not significantly different from cimetidine sites. There was no difference between the l‐NAME and combined l‐NAME plus cimetidine sites but these sites were significantly attenuated compared with control and cimetidine only sites (P < 0.05). These data suggest the rise in skin blood flow during whole body heating contains an H1 histamine receptor component but do not support an H2 histamine receptor component. Furthermore, part of the NO‐dependent component of active vasodilatation can be explained by H1 receptor activation.
Control of intracellular calcium in the presence of nitric oxide donors in isolated skeletal muscle fibres from mouse
Authors: Pouvreau Sandrine , Allard Bruno , Berthier Christine , Jacquemond Vincent
Published: September 2004

In skeletal muscle, nitric oxide (NO) is commonly referred to as a modulator of the activity of the ryanodine receptor (RyR) calcium release channel. However the reported effects of NO on isolated sarcoplasmic reticulum (SR) preparations and single ryanodine receptor (RyR) activity are diverse, and how NO affects SR calcium release and intracellular calcium homeostasis under physiological conditions remains poorly documented and hardly predictable. Here, we studied the effects of NO donors on membrane current and intracellular [Ca2+] in single skeletal muscle fibres from mouse, under voltage‐clamp conditions. When fibres were chronically exposed to millimolar levels of sodium nitroprusside (SNP) and challenged by short membrane depolarizations, there was a progressive increase in the resting [Ca2+] level. This effect was use‐dependent with the slope of rise in resting [Ca2+] being increased two‐fold when the depolarizing pulse level was raised from −20 to +10 mV. Analysis of the decay of the [Ca2+] transients suggested that cytoplasmic Ca2+ removal processes were largely unaffected by the presence of SNP. Also the functional properties of the dihydropyridine receptor were very similar under control conditions and in the presence of SNP. The resting [Ca2+] elevation due to SNP was accompanied by a depression of the peak calcium release elicited by pulses to +10 mV. The effects of SNP could be reproduced by the chemically distinct NO donor NOC‐12. They could be reversed upon exposure of the fibres to the thiol reducing agent dithiothreitol. Results suggest that large levels of NO produce a redox‐sensitive continuous leak of Ca2+ from the SR, through a limited number of release channels that do not close once they are activated by membrane depolarization. This SR Ca2+ leak and the resulting increase in resting [Ca2+] may be important in mediating the effects of excess NO on voltage‐activated calcium release.
Electrons in Finite-Sized Water Cavities: Hydration Dynamics Observed in Real Time
Authors: Paik D. Hern , Lee I-Ren , Yang Ding-Shyue , Baskin J. Spencer , Zewail Ahmed H.
Published: September 2004

We directly observed the hydration dynamics of an excess electron in the finite-sized water clusters of

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathrm{H}_{2}\mathrm{O})_{\mathrm{n}}^{-}\) \end{document}

with
n
= 15, 20, 25, 30, and 35. We initiated the solvent motion by exciting the hydrated electron in the cluster. By resolving the binding energy of the excess electron in real time with femtosecond resolution, we captured the ultrafast dynamics of the electron in the presolvated (“wet”) and hydrated states and obtained, as a function of cluster size, the subsequent relaxation times. The solvation time (300 femtoseconds) after the internal conversion [140 femtoseconds for

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathrm{H}_{2}\mathrm{O})_{35}^{-}\) \end{document}

] was similar to that of bulk water, indicating the dominant role of the local water structure in the dynamics of hydration. In contrast, the relaxation in other nuclear coordinates was on a much longer time scale (2 to 10 picoseconds) and depended critically on cluster size.
Hydrated Electron Dynamics: From Clusters to Bulk
Authors: Bragg A. E. , Verlet J. R. R. , Kammrath A. , Cheshnovsky O. , Neumark D. M.
Published: September 2004

The electronic relaxation dynamics of size-selected (H
2
O)

n

–
/(D
2
O)

n

[25 ≤
n
≤ 50] clusters have been studied with time-resolved photoelectron imaging. The excess electron (

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(e_{c}^{-}\) \end{document}

) was excited through the

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transition with an ultrafast laser pulse, with subsequent evolution of the excited state monitored with photodetachment and photoelectron imaging. All clusters exhibited p-state population decay with concomitant s-state repopulation (internal conversion) on time scales ranging from 180 to 130 femtoseconds for (H
2
O)

n

–
and 400 to 225 femtoseconds for (D
2
O)

n

–
; the lifetimes decrease with increasing cluster sizes. Our results support the “nonadiabatic relaxation” mechanism for the bulk hydrated electron (

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(e_{aq}^{-}\) \end{document}

), which invokes a 50-femtosecond

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internal conversion lifetime.
What is responsible for the carcinogenicity of PM2.5?
Authors: Harrison R M , Smith D J T , Kibble A J
Published: September 2004

Aims:To test whether exposure to known chemical carcinogens in the atmosphere is capable of explaining the association between concentrations of PM2.5and lung cancer mortality observed in the extended ACS Cohort Study.1

Methods:Taking account of possible cancer latency periods, lung cancer rates due to exposure to As, Cr(VI), Ni, and polycyclic aromatic hydrocarbons (PAHs) were calculated based on a review of historic measurements from the United States and the use of unit risk factors. The predicted rates were compared with rates of cancer attributable to PM2.5derived from data in the ACS study.1

Results:Despite many uncertainties, the lung cancer rates predicted due to exposure to US urban concentrations of the carcinogenic substances arsenic, nickel, chromium, and PAHs measured in 1960 and earlier (and hence allowing for a latency period) were within the range predicted on the basis of the ACS Cohort Study due to exposure of PM2.5. There are, however, many caveats, most particularly that for the chemical carcinogens to be responsible for the effects attributed to PM2.5by Pope and colleagues,1the concentrations of chemical carcinogens at the time of relevant exposures would need to be correlated with the concentrations of PM2.5in US urban areas measured between 1979 and 2000 and used in the ACS study.

Conclusions:While many uncertainties remain, it appears plausible that known chemical carcinogens are responsible for the lung cancers attributed to PM2.5exposure in the extended ACS Cohort Study. However, the possibility should not be ruled out that particulate matter is capable of causing lung cancer independent of the presence of known carcinogens.
Work related shoulder disorders: quantitative exposure-response relations with reference to arm posture
Authors: Svendsen S W , Bonde J P , Mathiassen S E , Stengaard-Pedersen K , Frich L H
Published: September 2004

Aims:To determine quantitative exposure-response relations between work with highly elevated arms and supraspinatus tendinitis, shoulder pain with disability, and shoulder pain without disability.

Methods:A cross sectional study was conducted in a historical cohort of 1886 males from three occupational groups. Exposure measurements were performed for four consecutive working days in a random sample of 72 currently employed subjects. Individual work histories were obtained by questionnaire and register data. Health status was ascertained by physical examination blinded towards exposure and symptoms. Data were analysed by generalised estimating equation and multiple logistic regression with adjustment for potential confounders.

Results:For current upper arm elevation above 90°, a duration increment of 1% of the daily working hours was associated with odds ratios of 1.23 (95% CI 1.10 to 1.39) for supraspinatus tendinitis, 1.16 (95% CI 1.08 to 1.24) for shoulder pain with disability, and 1.08 (95% CI 1.04 to 1.13) for shoulder pain without disability. The outcomes were not related to duration of employment in one of the three trades.

Conclusions:Quantitative exposure-response relations were established between current work with highly elevated arms and clinically verified shoulder disorders. Substantial long term cumulative effects were not shown. A potential for primary prevention was revealed.
A strategy for health surveillance in laboratory animal workers exposed to high molecular weight allergens
Authors: Meijer E , Grobbee D E , Heederik D
Published: September 2004

Aims:To develop a health surveillance strategy with the use of diagnostic and prognostic prediction models to detect and predict occupational allergic diseases efficiently.

Methods:Data from laboratory animal workers (n = 351) participating in an ongoing cohort study were used to develop diagnostic and prognostic models with logistic regression analyses. A diagnostic model was developed from questionnaire items, and exposure measurements to find predictors for the estimation of the probability of sensitisation to workplace allergens. With the resulting questionnaire model workers were divided into subgroups (high/low probability). A prognostic model was established in workers initially low sensitised using follow up data over a 2–3 year period. The accuracy of the models was evaluated by the concordance (c) statistic, and by comparison of the predicted and observed prevalence.

Results:A diagnostic rule, containing five questionnaire items, identified workers with a high risk of sensitisation. These workers showed high rates of work related asthma, allergic symptoms, doctor’s visit, and absenteeism. A prognostic rule based on four questionnaire items predicted workers at high risk of near future sensitisation with high rates of future (allergic) respiratory symptoms, and asthmatic attacks.

Conclusion:The risk of (future) sensitisation and the severity of laboratory animal allergy can be predicted accurately with diagnostic and prognostic prediction models based on questionnaire items. Workers with an increased risk of future sensitisation also showed serious allergic symptoms at follow up. Workers with a low risk have a low risk of becoming diseased in the future.
Impact of musculoskeletal co-morbidity of neck and upper extremities on healthcare utilisation and sickness absence for low back pain
Authors: IJzelenberg W , Burdorf A
Published: September 2004

Aims:To describe the presence of musculoskeletal co-morbidity of the neck and upper extremities among industrial workers with low back pain, and to examine whether it has an impact on healthcare utilisation and sickness absence for low back pain.

Methods:A self administered questionnaire was used to collect data from 505 industrial workers (response 86%).

Results:The 12 month prevalence of low back pain was 50%. Among subjects with low back pain the 12 month prevalence of musculoskeletal co-morbidity of the neck and upper extremities was 68%. Among workers with low back pain, subjects with high pain intensity or disabling low back pain were more likely to have musculoskeletal co-morbidity. In comparison to the subjects who report back pain only, subjects with co-morbidity showed worse general health and health related quality of life. No impact of upper extremity co-morbidity was found on healthcare utilisation, and sickness absence due to low back pain.

Conclusions:This study provides no evidence that musculoskeletal co-morbidity of the neck and upper extremities influences the choice to seek care or take sick leave due to low back pain among industrial manual workers. For occupational health practitioners the finding of a high co-morbidity is important to consider when implementing workplace interventions aimed at the reduction of specific musculoskeletal complaints, since the controls for one musculoskeletal complaint may impact adversely on another musculoskeletal complaint. Researchers who perform low back pain intervention studies using generic health measures, should take into account the impact of musculoskeletal co-morbidity on these measures.
Surveillance of noise exposure in the Danish workplace: a baseline survey
Authors: Kock S , Andersen T , Kolstad H A , Kofoed-Nielsen B , Wiesler F , Bonde J P
Published: September 2004

Aims:To evaluate an epidemiological approach to a national noise hazard surveillance strategy, and report current exposure levels in the Danish workplace.

Methods:A study base of 840 companies in 10 selected high risk industries in the largest county in Denmark was identified from a national register. Noise exposure was measured among manual workers recruited from a random sample of workplaces in each industry. For reference, financial companies and a sample of residents were investigated according to the same protocol. The A-weighted equivalent sound level (LAeq) for a full shift was measured by portable dosimeters worn by 830 workers employed at 91 workplaces (67% of 136 eligible companies).

Results:The epidemiological design proved feasible and established a baseline for future noise surveillance. Substantial resources were needed to motivate workplaces to enlist and the final participation rate was less than optimal (66.9%). The LAeq (8)values in the selected industries were highly elevated (mean 83.7 dB(A) (95% CI 83.3 to 84.1) in comparison with residents and office workers (mean 69.9 dB(A), 95% CI 68.8 to 71.0). Some 50% of the workers were exposed to more than 85 dB(A) and some 20% to more than 90 dB(A) in several industries.

Conclusion:Noise levels in Danish high risk industries remain high. A substantial proportion of workers are exposed to noise levels above the current threshold limit of 85 dB(A). Ongoing surveillance of noise exposure using full shift dosimetry of workers in random samples of workplaces most at risk to high noise levels may help reinforce preventive measures. Such a programme would benefit from compulsory workplace participation.