bluuebunny/crossref_metadata_2025 huggingface dataset:
Weibliche Subjektivität und das Versagen des sanften Patriarchen in Schnitzlers “Fräulein Else”
Authors: Prutti Brigitte
Published: May 2004

Der Aufsatz erörtert die moderne Verführungsfabel von Schnitzlers Erzählung “Fräulein Else” und das sozialpsychologische Profil seiner Protagonistin auf der Folie des bürgerlichen Trauerspiels im 18. Jahrhundert, insbesondere Lessing. Er zeigt, dass Schnitzlers subtiles psychologisches Porträt seiner Titelfigur auch als eine Auseinandersetzung mit dem Versagen des sanften Patriarchen aufgefasst werden kann, den die Schriftsteller der Aufklärung als Repräsentanten kleinfamilialer Intimität in die deutsche Literatur eingeführt hatten. Das geschieht anhand einer Diskussion des weiblichen Figurenbewusstseins und des Figurenhandelns an den beiden szenischen Höhepunkten der Novelle. In der abschließenden Erörterung von Elses Tod werden auch die fragwürdigen Aspekte von Schnitzlers Repräsentation des weiblichen Sterbens zur Diskussion gestellt.
GABABreceptors in Schwann cells influence proliferation and myelin protein expression
Authors: Magnaghi Valerio , Ballabio Marinella , Cavarretta Ilaria T. R. , Froestl Wolfgang , Lambert Jeremy J. , Zucchi Ileana , Melcangi Roberto C.
Published: May 2004

The location and the role of γ‐aminobutyric acid type B (GABAB) receptors in the central nervous system have recently received considerable attention, whilst relatively little is known regarding the peripheral nervous system. In this regard, here we demonstrate for the first time that GABABreceptor isoforms [i.e. GABAB(1)and GABAB(2)] are specifically localized in the rat Schwann cell population of the sciatic nerve. Using the selective GABABagonist [i.e. (–)‐baclofen] and the antagonists (i.e. CGP 62349, CGP 56999 A, CGP 55845 A), such receptors are shown to be functionally active and negatively coupled to the adenylate cyclase system. Furthermore, exposure of cultured Schwann cells to (–)‐baclofen inhibits their proliferation and reduces the synthesis of specific myelin proteins (i.e. glycoprotein Po, peripheral myelin protein 22, myelin‐associated glycoprotein, connexin 32), providing evidence for a physiological role of GABABreceptors in the glial cells of the peripheral nervous system.
Long‐lasting nicotinic modulation of GABAergic synaptic transmission in the rat nucleus accumbens associated with behavioural sensitization to amphetamine
Authors: De Rover Mischa , Mansvelder Huibert D. , Lodder Johannes C. , Wardeh George , Schoffelmeer Anton N. M. , Brussaard Arjen B.
Published: May 2004

A robust increase in dopaminergic transmission in the nucleus accumbens (NAc) shell has been reported to be consistently associated with the long‐term expression of behavioural sensitization to drugs of abuse. However, little is known about how this affects the neuronal network of the NAc. We made cellular recordings in NAc slices of saline‐ and amphetamine‐pretreated adult rats and found that expression of behavioural sensitization was associated with long‐lasting changes in the basal firing pattern of cholinergic interneurons up to 3 weeks after the last drug injection. Consequently, upon amphetamine sensitization, an inhibiting effect of the nicotinic receptor blocker mecamylamine on the amplitudes of spontaneous GABAergic synaptic currents as well as on the failure rate of electrically evoked GABAergic currents was found that was not present under control conditions. Thus, behavioural sensitization to amphetamine is associated with an up‐regulation of the endogenous activation of nicotinic receptors that, in turn, stimulate the GABAergic synaptic transmission within the NAc shell. This is a new mechanism by which drugs of abuse may induce alterations in the processing and integration of NAc inputs involved in psychomotor sensitization.
Dendritic spine pathology and deficits in experience‐dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice
Authors: Spires Tara L. , Grote Helen E. , Garry Sylvia , Cordery Patricia M. , Van Dellen Anton , Blakemore Colin , Hannan Anthony J.
Published: May 2004

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD. Enriching the environment of HD transgenic mice delays the onset of symptoms, so we also examine the effects of enrichment on dendrite pathology. Golgi‐impregnated tissue from symptomatic R6/1 HD mice reveals a decrease in dendritic spine density and dendritic spine length in striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a specific reduction in the proportion of bifurcated dendritic spines on basal dendrites of cortical pyramidal neurons. No differences in soma size, recurving distal dendrites, or dendritic branching were observed. Although home‐cage environmental enrichment from 1 to 8 months of age increases spine density in wild‐type mice, it has no effect on the spine pathology in HD mice. These results show that dendritic spine pathology in R6/1 HD mice resembles degenerative changes seen in human HD and in other transgenic mouse models of the disease. We thus provide further evidence that the HD mutation disrupts the connectivity in both neostriatum and cerebral cortex, which will contribute to motor and cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease pathology interferes with the normal plastic response of dendritic spines to environmental enrichment.
Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2‐mediated direct suppression and M1/M3‐mediated indirect suppression through endocannabinoid signalling
Authors: Fukudome Yuko , Ohno‐Shosaku Takako , Matsui Minoru , Omori Yuko , Fukaya Masahiro , Tsubokawa Hiroshi , Taketo Makoto M. , Watanabe Masahiko , Manabe Toshiya , Kano Masanobu
Published: May 2004

The cholinergic system in the CNS plays important roles in higher brain functions, primarily through muscarinic acetylcholine receptors. At cellular levels, muscarinic activation produces various effects including modulation of synaptic transmission. Here we report that muscarinic activation suppresses hippocampal inhibitory transmission through two distinct mechanisms, namely a cannabinoid‐dependent and cannabinoid‐independent mechanism. We made paired whole‐cell recordings from cultured hippocampal neurons of rats and mice, and monitored inhibitory postsynaptic currents (IPSCs). When cannabinoid receptor type 1 (CB1) was blocked, oxotremorine M (oxo‐M), a muscarinic agonist, suppressed IPSCs in a subset of neuron pairs. This suppression was associated with an increase in paired‐pulse ratio, blocked by the M2‐prefering antagonist gallamine, and was totally absent in neuron pairs from M2‐knockout mice. When CB1 receptors were not blocked, oxo‐M suppressed IPSCs in a gallamine‐resistant manner in cannabinoid‐sensitive pairs. This suppression was associated with an increase in paired‐pulse ratio, blocked by the CB1 antagonist AM281, and was completely eliminated in neuron pairs from M1/M3‐compound‐knockout mice. Our immunohistochemical examination showed that M2 and CB1 receptors were present at inhibitory presynaptic terminals of mostly different origins. These results indicate that two distinct mechanisms mediate the muscarinic suppression. In a subset of synapses, activation of M2 receptors at presynaptic terminals suppresses GABA release directly. In contrast, in a different subset of synapses, activation of M1/M3 receptors causes endocannabinoid production and subsequent suppression of GABA release by activating presynaptic CB1 receptors. Thus, the muscarinic system can influence hippocampal functions by controlling different subsets of inhibitory synapses through the two distinct mechanisms.
Depression of GABAergic input to identified hippocampal neurons by group III metabotropic glutamate receptors in the rat
Authors: Kogo Naoki , Dalezios Yannis , Capogna Marco , Ferraguti Francesco , Shigemoto Ryuichi , Somogyi Peter
Published: May 2004

The release of GABA in synapses is modulated by presynaptic metabotropic glutamate receptors (mGluRs). We tested whether GABA release to identified hippocampal neurons is influenced by group III mGluR activation using the agonist L‐(+)‐2‐amino‐4‐phosphonobutyric acid (L‐AP4) on inhibitory postsynaptic currents (IPSCs) evoked in CA1 interneurons and pyramidal cells. In interneurons, characterized with biocytin and immunolabelling for somatostatin, evoked IPSCs were depressed by 50 µm L‐AP4 (activating mGluR4 and 8) to 68 ± 6% of control, but they were rarely depressed in pyramidal cells (96 ± 4% of control). At 300–500 µm concentration (activating mGluR4, 7 and 8), L‐AP4 depressed IPSCs in both interneurons (to 70 ± 6%) and pyramidal cells (to 67 ± 4%). The change in trial‐to‐trial variability and in paired‐pulse depression indicated a presynaptic action. In interneurons, the degree of IPSC depression was variable (to 9–87%), and a third of IPSCs were not affected by L‐AP4. The L‐AP4‐evoked IPSC depression was blocked by LY341495. The depression of IPSCs was similar in O‐LM cells and other interneurons. The lack of cell‐type selectivity and the similar efficacy of different concentrations of L‐AP4 suggest that several group III mGluRs are involved in the depression of IPSCs. Electron microscopic immunocytochemistry confirmed that mGluR4, mGluR7a and mGluR8a occur in the presynaptic active zone of GABAergic terminals on interneurons, but not on those innervating pyramidal cells. The high variability of L‐AP4‐evoked IPSC suppression is in line with the selective expression of presynaptic mGluRs by several distinct types of GABAergic neuron innervating each interneuron type.
GABAergic modulation of DC stimulation‐induced motor cortex excitability shifts in humans
Authors: Nitsche Michael A. , Liebetanz David , Schlitterlau Anett , Henschke Undine , Fricke Kristina , Frommann Kai , Lang Nicolas , Henning Stefan , Paulus Walter , Tergau Frithjof
Published: May 2004

Weak transcranial DC stimulation (tDCS) of the human motor cortex results in excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances excitability, whereas cathodal stimulation reduces it. Although the after‐effects of tDCS are NMDA receptor‐dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after‐effects elicited by anodal tDCS. Administration of the GABAA receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS‐induced excitability elevation. The initial absence of an excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS‐generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late‐occurring excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre‐tDCS values, excitability changes originating from remote cortical or subcortical areas could be involved.
Determinants of Cross‐Sectional Variation in Discount Rates, Growth Rates and Exit Cap Rates
Authors: Gunnelin Åke , Hendershott Patric H. , Hoesli Martin , Söderberg Bo
Published: May 2004

This study investigates the determinants of key input variables in valuers' discounted cash flow models used for estimating market values for offices. Data from 599 valuations in 2000 from Stockholm, Gothenburg and Malmö are used to explain variation in discount rates, expected growth rates in net operating income and exit cap rates. Our ability to explain the relatively wide variation in appraisal assumptions with plausible covariates generates confidence in the appraisal process. This has important implications because most value and returns indices of commercial real estate worldwide are appraisal based.
An Analysis of the Determinants of Transaction Frequency of Institutional Commercial Real Estate Investment Property
Authors: Fisher Jeffrey , Gatzlaff Dean , Geltner David , Haurin Donald
Published: May 2004

This study examines the correlation of the frequency of the sale of investment‐grade property with national, regional and local variables, including property‐ and owner‐specific characteristics. More specifically, the study identifies the primary factors that “explain” intertemporal changes in transaction frequency in the underlying properties used to develop the National Council of Real Estate Investment Fiduciaries (NCREIF) index. Understanding these factors yields important information that can be used by firms when forming market expectations and developing investment strategies.
Ceftriaxone‐associated biliary sludge and pseudocholelithiasis during childhood: A prospective study
Authors: Bor Ozcan , Dinleyici Ener Cagri , Kebapci Mahmut , Aydogdu Sultan Durmus
Published: May 2004

Abstract
Background
: Cholelithiasis is a rare condition seen during childhood. The aim of this study was to determine frequency of biliary sludge and cholelithiasis with ceftriaxone therapy.

Methods
: Thirty‐eight children aged between 1 month and 17 years were evaluated with ultrasonographic examination at the initiation of the ceftriaxone therapy and 10th day of therapy, consecutively. If biliary sludge or cholelithiasis were demonstrated, scans were repeated monthly until pathology disappeared.

Results
: Abnormal gallbladder sonograms were demonstrated in 36.8% (n = 14) of patients at the 10th day of therapy. Cholelithiasis was detected in 28.9% (n = 11) of patients and biliary sludge was detected in 7.9% (n = 3). Two children still had cholelithiasis at the 30th day after therapy and one had cholelithiasis after the 60th day. The 9‐year‐old girl who still had cholelithiasis after 60 days of therapy also had nausea, vomiting and abdominal pain at 7 days after cessation of therapy. Her 90th day sonographic examination was normal.

Conclusion
: Reversible biliary sludge or pseudocholelithiasis due to ceftriaxone treatment is not a rare condition. Therefore it is benign, spontaneously resolved and clinical signs are usually absent.
Endothelins and their inhibition in the human skin microcirculation: ET[1−31], a new vasoconstrictor peptide
Authors: Leslie Stephen J. , Rahman Mamun Q. , Denvir Martin A. , Newby David E. , Webb David J.
Published: May 2004

Aims  Endothelin‐1 (ET‐1[1−21]) is an extremely potent vasoconstrictor in the human skin microcirculation and is generated from larger precursor peptides. The aims of the present study were to assess the vasoactive effects of these precursors as well as endothelin blockade in the human skin microcirculation, in vivo.

Methods  Six healthy volunteers received intradermal injections of a range of doses of big ET‐1[1−38], ET‐1[1−31], ET‐1[1−21], BQ‐123 (ETA receptor antagonist), BQ‐788 (ETB receptor antagonist), phosphoramidon [endothelin converting enzyme (ECE) inhibitor] or saline control (0.9%). Skin blood flow (SBF) was measured using standard laser Doppler flowmetry.

Results  Big ET‐1[1−38], ET‐1[1−31] and ET‐1[1−21] reduced SBF when compared with saline control (P < 0.01 for all). Big ET‐1[1−38] and ET‐1[1−31] were less potent than ET‐1[1−21] as defined by skin vasoconstriction. Phosphoramidon, BQ‐123 and BQ‐788, given alone, all caused vasodilatation in the human skin microcirculation (P < 0.01 for all).

Conclusions  In the human skin microcirculation, big ET‐1[1−38] and ET‐1[1−31] are less potent vasoconstrictors than ET‐1[1−21]. The effects of big ET‐1[1−38] and phosphoramidon suggest the presence of endogenous ECE activity in the skin. In contrast to skeletal muscle resistance vessels, ET‐1[1−21] contributes to the maintenance of skin microvascular tone through both ETA and ETB receptor‐mediated vasoconstriction.
Leflunomide in active rheumatoid arthritis: a prospective study in daily practice
Authors: Van Roon E. N. , Jansen T. L. TH. A. , Mourad L. , Houtman P. M. , Bruyn G. A. W. , Griep E. N. , Wilffert B. , Tobi H. , Brouwers J. R. B. J.
Published: May 2004

Aims

We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care‐as‐usual.

Methods

In this prospective case series study, from outpatient medical records a standard dataset was collected including patient and disease characteristics, data on leflunomide use and adverse drug reactions.

Results

During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow‐up duration was 317 (11–911) days. Sixty‐five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow‐up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient‐years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS28) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow‐up, respectively. Within a 12‐month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS28 response criteria.

Conclusions

In the setting of care‐as‐usual, rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within a year after start of leflunomide treatment, mainly because of adverse drug reactions.
Relationship between Type A and B personality and debrisoquine hydroxylation capacity
Authors: Gan S. H. , Ismail R. , Wan Adnan W. A. , Zulmi W. , Kumaraswamy N. , Larmie E. T.
Published: May 2004

Aim

A person with Type A personality is an ‘aggressor’ compared with the rarely harried Type B. Although debrisoquine hydroxylase (CYP2D6) capacity has been associated with personality, no study has specifically investigated its association with personality Type A and B. Therefore the aim of this research was to study the impact of CYP2D6 on Type A and B personality.

Methods

Type A and B personality questionnaires were administered to 48 healthy patients undergoing elective orthopaedic surgery. After obtaining informed consent, patients were genotyped for the various CYP2D6 alleles by allele‐specific polymerase chain reaction. Based on the genotypes, patients were grouped as extensive metabolizer (EM)1 (normal) (CYP2D6*1/*1), EM2 (intermediate) (CYP2D6*1/*4, CYP2D6*1/*5, CYP2D6*1/*9 and CYP2D6*1/*10) and EM3 (slow) (CYP2D6*4/*10, CYP2D6*5/*10, CYP2D6*10/*10 and CYP2D6*10/*17). χ2 was used to determine the relationship between the groups and personality types.

Results

The percentages of patients who were of the EM1, EM2 and EM3 groups were 20.8%, 52.1% and 27.1%, respectively. There was a significant difference (P = 0.032) between the three groups in terms of personality type, in which EM1 showed a tendency to be of personality Type A while EM2 and EM3 tended to be of personality Type B.

Conclusion

The study suggests that there is a relationship between CYP2D6 activity and Type A and B personality.
Bisphosphonate use and subsequent prescription of acid suppressants
Authors: Roughead E. E. , McGeechan K. , Sayer G. P.
Published: May 2004

Aim

To determine the extent of prescribing of acid suppression agents associated with initiation of bisphosphonate therapy.

Methods

This was a case control study, performed within the General Practice Network, Australia. The main outcome measure was re‐attendance within six weeks from index bisphosphonate prescription for acid supression agents.

Results

Of the bisphosphonate cases, 2.9%[95% confidence interval (CI) 1.8, 3.9] returned within 6 weeks for a prescription for proton pump inhibitor, histamine 2 receptor antagonist or antacid, compared with 0.9% of control patients (95% CI 0.5, 1.2). However, the bisphosphonate cases had significantly higher rates of previous use of nonsteroidal anti‐inflammatory agents. After controlling for previous nonsteroidal anti‐inflammatory drug use, the increased use of acid suppression agents was statistically significant, the odds ratio = 3.21 (95% CI 2.02, 5.11).

Conclusion

Bisphosphonate use appears to be associated with increased use of acid suppressant agents within 6 weeks of first supply.
Population pharmacokinetics of total and unbound plasma cisplatin in adult patients
Authors: Urien Sail , Lokiec François
Published: May 2004

Aims

To investigate the pharmacokinetics of unbound (ultrafilterable) and total plasma platinum using a population approach and to identify patient characteristics that may influence the disposition of the drug.

Methods

Pharmacokinetic and demographic data were collected from adult patients treated with 30‐min daily infusions of cisplatin for various malignancies. Unbound and total platinum concentration‐time data were analysed using a nonlinear mixed effects model.

Results

Data from 43 patients were available for analysis. A linear two‐compartment model best described total and unbound platinum plasma concentration‐time data. The mean population estimates for total and unbound drug were, respectively, 0.68 and 35.5 l h−1 for clearance and 21.1 and 23.4 l for central distribution volume (V1). Unbound clearance (CL) was dependent on body surface area (BSA) and creatinine clearance, and V1 was dependent on BSA. The elimination rate constant for plasma‐bound platinum (modelled as metabolite formation) was 0.014 h−1. The pharmacokinetic parameter, fm/Vm, a measure of the clearance of unbound platinum due to irreversible plasma binding, was related to serum protein concentration and to the inverse of dose per m2. The covariate modelling of CL, V1 and fm/Vm improved the intersubject variabilities associated with these parameters. The final pharmacokinetic models were validated using 200 bootstrap samples from the original datasets.

Conclusions

The results support the conventional dose adjustment of cisplatin based on BSA. They also support the need for a dose reduction in case of renal insufficiency.
The revision of the Declaration of Helsinki: past, present and future
Authors: Carlson Robert V. , Boyd Kenneth M. , Webb David J.
Published: May 2004

The World Medical Association's Declaration of Helsinki was first adopted in 1964. In its 40‐year lifetime the Declaration has been revised five times and has risen to a position of prominence as a guiding statement of ethical principles for doctors involved in medical research. The most recent revision, however, has resulted in considerable controversy, particularly in the area of the ethical requirements surrounding placebo‐controlled trials and the question of responsibilities to research participants at the end of a study. This review considers the past versions of the Declaration of Helsinki and asks the question: How exactly has the text of the Declaration changed throughout its lifetime? Regarding the present form of the Declaration of Helsinki we ask: What are the major changes in the most recent revision and what are the controversies surrounding them? Finally, building on the detailed review of the past and present versions of the Declaration of Helsinki, we give consideration to some of the possible future trajectories for the Declaration in the light of its history and standing in the world of the ethics of medical research.
Endocrine complications of high‐dose therapy with stem cell transplantation
Authors: Sanders Jean E.
Published: May 2004

Abstract:  Evaluations of endocrine function following hematopoietic cell transplantation demonstrate that the endocrine function abnormalities observed are related to the type of transplant preparative regimen received. Children given high dose cyclophosphamide (CY) only have normal thyroid function, normal growth and development. Children who received a busulfan (BU) plus CY preparative regimen usually have normal thyroid function, normal prepubertal growth, delayed or absent pubertal development, and blunted post‐pubertal growth. Recipients of preparative regimens containing total body irradiation may be anticipated to have some thyroid dysfunction, impaired growth rates and delayed or absent pubertal development. Post‐pubertal teens and young adults are likely to have gonadal function recover if they received a preparative regimen with CY only but are likely to have primary gonadal failure if they received a preparative regimen with BU or total body irradiation. Individuals whose gonadal function becomes normal have become parents of normal children. All patients who receive a marrow transplant should be followed long‐term for development of endocrine function abnormalities.
Recent advances in the prevention of CMV infection and disease after hematopoietic stem cell transplantation
Authors: Boeckh Michael , Fries Bettina , Garrett Nichols W.
Published: May 2004

Abstract:  Cytomegalovirus (CMV) remains an important pathogen in hematopoietic stem cell transplant (HCT) recipients in the current era of antiviral prophylaxis and preemptive therapy, despite the almost complete elimination of CMV disease during the first 3 months after transplantation. Pretransplant CMV serostatus of the donor and/or recipient remains an important risk factor for poor post‐transplant outcome, especially in highly immunodeficient patients (e.g. recipients of ex vivo or in vivo T‐cell depletion). Prevention of late CMV disease continues to be a challenge in selected high‐risk populations, and indirect immunomodulatory effects of CMV (e.g. invasive bacterial and fungal infections) appear to contribute to the poor outcome. The risk of developing antiviral resistance remains low in most patients; however, in a setting of intense immunosuppression (e.g. after transplantation from a haploidentical donor) the incidence may be as high as 8%. Transfusion‐transmitted CMV infection can be reduced by the provision of seronegative or leukocyte‐depleted blood products; however, a small risk of 1–2% of CMV disease remains. Surveillance and preemptive therapy is effective in preventing transfusion‐related CMV disease. The development of new drugs and immunologic strategies (adoptive transfer of CMV‐specific T‐cells and donor/recipient vaccination strategies) are important goals for the elimination of the negative impact of CMV in the HCT setting.
Megatherapy and stem cell transplantation for Ewing's family of tumors: A critical review of current literature
Authors: Kalambakas Stacey A , Moore Theodore B , Feig Stephen A
Published: May 2004

Abstract:  Although a multimodal approach consisting of chemotherapy and local control with surgery and/or radiation has improved survival in children with Ewing's sarcoma family of tumors, the prognosis for patients with high‐risk disease remains poor. More aggressive treatments with high‐dose myeloablative chemotherapy followed by stem cell rescue have been utilized in an attempt to improve survival in these patients. Although many studies have been published, it is difficult to interpret the data since patient populations were heterogeneous with respect to disease stage, prior therapy, conditioning and stem cell source. Furthermore, there was no uniform definition of high risk, the sample sizes were small and most studies lacked appropriate control groups. Assessment of the utility of megatherapy will require prospective controlled studies.
Application of stem cell transplant for brain tumors
Authors: Gardner Sharon L.
Published: May 2004

Abstract:  Brain tumors are the second most common malignancy in children and the most common solid tumor. The majority of children are treated with surgery alone or in combination with radiation and/or chemotherapy. Recently investigators have used high dose chemotherapy with autologous stem cell rescue (ASCR) in patients with malignant brain tumors. This approach has been most successful in chemosensitive tumors including medulloblastoma, supratentorial primitive neuroectodermal tumors (SPNET) and central nervous system germ cell tumors (CNS GCT). In addition, the use of high dose chemotherapy has enabled the reduction and in many cases elimination of radiation therapy to very young children. To date there have been no prospective randomized studies comparing high dose chemotherapy and ASCR with conventional therapy. Radiation therapy is often not an option for patients with recurrent disease and conventional dose chemotherapy rarely if ever results in long‐term survival. Unfortunately, the majority of studies using conventional therapy in order to delay irradiation in young children newly diagnosed with malignant brain tumors have been unsuccessful. Although the numbers are small, preliminary data suggest that not only is survival but also quality of life is superior with the use of high dose chemotherapy. Future studies will most likely include the use of new agents as part of the cytoreduction. In addition, through the use of peripheral blood stem cells and improvements in supportive care, multiple courses of high dose chemotherapy can be administered. High dose chemotherapy with ASCR is a foundation upon which many different types of therapies can be built. Several possibilities include the use of anti‐angiogenesis agents, monoclonal antibodies and biologic response modifiers.
Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentration
Authors: Wang J , Huff AM , Spence JD , Hegele RA
Published: May 2004

Plasma total homocysteine (tHcy) concentration, an independent risk factor of atherosclerosis, has numerous genetic and environmental determinants. While the thermolabile polymorphism in MTHFR encoding methylenetetrahydrofolate reductase is the best‐studied genetic factor associated with variation in plasma tHCy, other candidate genes are being evaluated. Recently, we discovered that cystathioninuria was caused by mutations in the CTH gene encoding cystathionine γ‐lyase, an enzyme that converts cystathionine to cysteine in the trans‐sulfuration pathway. We also identified a common single nucleotide polymorphism (SNP), namely c.1364G>T (S403I) in exon 12 of CTH. In the current analysis, we studied the association of genotypes of this SNP with plasma tHcy concentrations in 496 Caucasian subjects. CTH 1364T/T homozygotes had significantly higher mean plasma tHcy concentration than subjects with other genotypes, and the effect sizes of CTH and MTHFR genotypes were similar. The findings suggest that common variation in CTH may be a determinant of plasma tHcy concentrations.
Incidental neurodevelopmental episodes in the etiology of schizophrenia: An expanded model involving epigenetics and development
Authors: Singh SM , McDonald P , Murphy B , O'Reilly R
Published: May 2004

Epidemiological data favors genetic predisposition for schizophrenia, a common and complex mental disorder in most populations. Search for the genes involved using candidate genes, positional cloning, and chromosomal aberrations including triplet repeat expansions have established a number of susceptibility loci and genomic sites but no causal gene(s) with a proven mechanism of action. Recent genome‐wide gene expression studies on brains from schizophrenia patients and their matched controls have identified a number of genes that show an alteration in expression in the diseased brains. Although it is not possible to offer a cause and effect association between altered gene expression and disease, such observations support a neurodevelopmental model in schizophrenia. Here, we offer a mechanism of this disease, which takes into account the role of developmental noise and diversions of the neural system. It suggests that the final outcome of a neural developmental process is not fixed and exact. Rather it develops with a variation around the mean. More important, the phenotypic consequence may cross the norm as a result of fortuitous and/or epigenetic events. As a result, a normal genotype may develop as abnormal with a disease phenotype. More important, susceptible genotypes may have reduced penetrance and develop as a normal phenocopy. The incidental episodes in neurodevelopment will explain the frequency of schizophrenia in most populations and high discordance of monozygotic twins.
Should Australia introduce a vaccine injury compensation scheme?
Authors: Isaacs D
Published: May 2004

Abstract:  At least a dozen countries or states in the world have introduced vaccine injury compensation schemes. This paper argues that the Australian Government should introduce such a scheme, which may reduce litigation, and may improve consumer and provider confidence. The most important justification, however, is an ethical argument from justice and equity: introduction of a vaccine injury compensation scheme acknowledges the unique situation that routine childhood immunization is a public health measure, given and accepted in good faith, that may occasionally damage the recipient.
Bridging the gap between health and education: Words are not enough
Authors: O'Keeffe MJ , McDowell M
Published: May 2004

Objectives:  When using specific terminology for childhood developmental disorders, paediatricians make assumptions about what teachers know and believe. If these assumptions are incorrect, collaborative management may be compromised. We surveyed primary school teachers in North Brisbane regarding their beliefs about developmental disorders and their views on collaboration between medical and educational professionals.

Methods:  A survey questionnaire was written specifically, and then piloted with professional colleagues and 40 teachers. Questions examined teachers’ opinions about, and personal experience with various developmental disorders. Free comments addressed barriers to collaboration with doctors, and how this might be improved. Responses were analysed using descriptive statistics.

Results:  Responses were received from all of the 41 schools surveyed. Overall, completed questionnaires were obtained from 297 of 397 (75%) primary classroom teachers surveyed. Several apparent misconceptions were held, either by the majority (e.g. 70% felt dietary modification is commonly successful treatment for ADHD), or by a significant minority of teachers (e.g. 23% believed autistic spectrum disorder is not a permanent neurological condition). Responses to many questions concurred with the authors’ assumptions. Teachers reported high levels of concern about lack of training and resource support for managing special‐needs children. Over three‐quarters of teachers did not access doctors for information, relying instead on special education professionals (96%) or parents (94%). Few group differences were noted by age, sex, years teaching experience, or system (Catholic, State). Free comments identified significant barriers to the collaboration process, and suggested strategies to address these.

Conclusions:  Doctors cannot assume teachers’ beliefs about developmental disorders are similar to their own. Furthermore, doctors should recognize constraints that teachers work under, and can take the initiative to improve collaboration with topic‐based as well as child‐specific information.
A randomized trial of two dexamethasone regimens to reduce side‐effects in infants treated for chronic lung disease of prematurity
Authors: Odd DE , Armstrong DL , Teele RL , Kuschel CA , Harding JE
Published: May 2004

Objective:  Dexamethasone has been widely used to reduce the incidence of chronic lung disease in preterm infants. However side‐effects are common, and the ideal dose of dexamethasone has not been identified. We aimed to determine whether an individualized course of dexamethasone given to preterm babies at risk of chronic lung disease reduced the total dose of dexamethasone administered and reduced side‐effects compared with a standard 42‐day course.

Methods:  Thirty‐three infants in a regional neonatal unit with a birthweight of ≤1250 g who required mechanical ventilation at 7 days of age were randomly assigned to a 42‐day course of dexamethasone or an individualized course tailored to their respiratory status. The primary outcome was linear growth at 36 weeks corrected gestational age.

Results:  Infants in the individualized course received a 40% lower total dose of dexamethasone. However, there was no difference between the two groups in linear growth or in the incidence of any other side‐effects of treatment. There was also no difference in respiratory status or neurodevelopmental outcome.

Conclusion:  The individualized course of dexamethasone used in this study reduced the total dose of dexamethasone administered but did not significantly reduce side‐effects of treatment or alter outcome in infants at risk of chronic lung disease.
Obesity and under‐nutrition in a tertiary paediatric hospital
Authors: O'Connor J , Youde LS , Allen JR , Baur LA
Published: May 2004

Objective:  (i) To determine the prevalence of over‐ and under‐nutrition in both inpatients and outpatients in a tertiary paediatric hospital; (ii) to compare the prevalence of over‐nutrition with that in the Australian community and (iii) to determine whether nutritional status has an impact on length of stay in hospital.

Methods:  Patients aged over 12 months were proportionately sampled from medical and surgical wards and outpatient clinics. Data were collected for 245 inpatients (54% male) and 272 outpatients (55% male). Children's height, weight and body mass index (kg/m2) were measured. Overweight, obesity and under‐nutrition were defined according to international criteria. Prevalence of overweight and obesity was compared with that in the 1995 Australian National Nutrition Survey (NNS).

Results:  Similar proportions of inpatients and outpatients were underweight (6%) and wasted (4%). The prevalence of overweight and obesity in inpatients (22%) was similar to the NNS but was significantly higher in outpatients (32%, P < 0.0001). In a regression model to predict inpatient length of stay, nutritional status (P = 0.004) and the interaction between age and nutritional status (P = 0.009) were significant predictors. For over‐nourished inpatients, length of stay increased significantly with age. For normally nourished and under‐nourished inpatients, length of stay was relatively constant, regardless of age.

Conclusions:  There is a high prevalence of over‐nutrition in paediatric patients, and increased length of stay for older over‐nourished inpatients. These issues need to be addressed in terms of opportunities for intervention and impact on hospital resources.
Delayed disseminated Staphylococcus aureus infection following chickenpox
Authors: Raja Lope RJ , Goldstein AR , Gray JW
Published: May 2004

Abstract:  Chickenpox is generally a benign childhood disease. Bacterial superinfection is the commonest complication, and can be severe and life‐threatening. We describe a 15‐year‐old boy with disseminated Staphylococcus aureus infection following chickenpox.
Status dystonicus and Hallervorden‐Spatz disease: Treatment with intrathecal baclofen and pallidotomy
Authors: Kyriagis M , Grattan‐Smith P , Scheinberg A , Teo C , Nakaji N , Waugh M
Published: May 2004

Abstract:  Severe dystonia or status dystonicus is a life threatening disorder that develops in patients with both primary and secondary dystonia. We present the case of a 9‐year‐old boy with Hallervorden‐Spatz disease (HVS) who developed status dystonicus, failing to respond to high dose oral therapy with multiple antidystonic agents. High dose intravenous sedating agents combined with endotracheal intubation and mechanical ventilation were required to control the spasms. Alleviation of the spasms was achieved by a combination of temporary intrathecal baclofen infusions and bilateral pallidotomy. Although it could be argued this is a situation where only palliative measures should be used, we believe a relatively aggressive approach was justified. It relieved the intense pain associated with the spasms and allowed the child to be discharged home without the prolonged stay in intensive care, morbidity and mortality, which characterize status dystonicus.
A new species of Closterocerus Westwood (Hymenoptera: Eulophidae), a parasitoid of serpentine leafminers (Diptera: Agromyzidae) from Australia
Authors: Edwards Claire M , La Salle John
Published: May 2004

Abstract  Closterocerus mirabilis sp. n. is described from Victoria, Australia. This species is a parasitoid of several species of leafmining Agromyzidae, and a potential biological‐control agent for invasive agromyzid species. Due to the generalist nature of leafmining pests, conservation biological control utilising indigenous natural enemies should be the starting point for sustainable control measures against newly invading pests. This new species becomes part of the knowledge base for creating a contingency plan against invasive dipterous leafminers.
Response of Culicoides spp. (Diptera: Ceratopogonidae) to light‐emitting diodes
Authors: Bishop Alan L , Worrall Ross , Spohr Lorraine J , McKenzie Harry J , Barchia Idris M
Published: May 2004

Abstract  Light traps with incandescent globes are used in a national monitoring program to detect the presence of Culicoides spp. responsible for the transmission of viruses to livestock and native animals. Recent events have suggested that the efficiency of these traps should be reconsidered and possibly improved. Subsequently, the response of eight species of Culicoides to light‐emitting diodes (LEDs) was determined at two locations in New South Wales. Culicoides austropalpalis Lee & Reye, C. bunrooiensis Lee & Reye and C. marksi Lee & Reye were attracted to blue light. Responses to blue and green light could not be separated for C. bundyensis Lee & Reye, C. dycei Lee & Reye, C. nattiensis Lee & Reye and C. victoriae Macfie. Culicoides brevitarsis Kieffer was significantly attracted to green light. This species is the major vector of Akabane and bluetongue viruses in Australia. These responses were all significantly greater than the responses to the incandescent lights currently used in the light traps. The response to red light was less than the response to incandescent light for all species. Catches of C. brevitarsis were also related to the intensity of the green LEDs. These were more effective than the currently used incandescent globes at intensities between 46% and 142% of the incandescent intensity.
Distribution and biogeography of Bactrocera and Dacus species (Diptera: Tephritidae) in Papua New Guinea
Authors: Clarke Anthony R , Balagawi Solomon , Clifford Barbara , Drew Richard A I , Leblanc Luc , Mararuai Amanda , McGuire Daniel , Putulan David , Romig Travis , Sar Sim , Tenakanai David
Published: May 2004

Abstract  Based on literature records and the results of an extensive trapping program, presence records for 194 species of Bactrocera and Dacus in the 19 provinces of Papua New Guinea (PNG) are presented. Of the 770 records, over 500 are new. Based on species accumulation curves, Central, Morobe, Madang, Eastern Highlands, Western Highlands, New Ireland and Bougainville provinces, plus the province pairs of East and West Sepik, East and West New Britain, and Southern Highlands and Enga, can be regarded as having been adequately sampled. The remaining provinces should still be regarded as being under‐collected. On mainland PNG, Morobe and Central provinces have the richest faunas and highest levels of endemism, approximately 15% each. All other mainland provinces have very low levels of endemism and are essentially subsets of the faunas of Morobe and Central Province. Although also with very low levels of endemism, the Highlands provinces have a statistically distinct fauna, suggesting that a pool of the PNG species are able to utilise both lowland and highland habitats. The fruit fly fauna of the island provinces is distinct from the mainland fauna, with further separation between the islands of the Bismark Archipelago (New Britain and New Ireland) and Bougainville. The greatest diversity of flies in PNG are associated with major northern geological elements, i.e., the New Guinea orogen, New Guinea accreted terranes and the off‐shore islands, rather than the primary southern geological element, the Australian creton.
Australian species of the genusOpiusWesmael (Hymenoptera: Braconidae) attacking leaf‐mining Agromyzidae, with the description of a new species from South‐east Asia
Authors: Belokobylskij Sergey A , Wharton Robert A , La Salle John
Published: May 2004

Abstract The species ofOpiusWesmael that attack leaf‐mining Agromyzidae in Australia are discussed, and a key provided for their separation.Opius cinerariaeFischer is redescribed based on specimens reared fromLiriomyza chenopodii(Watt) (Agromyzidae), and its subgeneric placement is discussed in light of newly discovered morphological features.Opius (Opiothorax) chromatomyiaeBelokobylskij & Wharton sp. n. is described from specimens reared fromChromatomyia horticola(Goureau) andLiriomyza huidobrensis(Blanchard) (Agromyzidae) in Malaysia, Indonesia and Vietnam.Opius insulicolaTobias nom. n. is proposed forOpius insularisTobias (1998), a junior primary homonym.
Panchaetothrips timonii sp. n. (Thysanoptera, Thripidae); first Australian record of this Old World tropical genus
Authors: Mound Laurence A , Postle Anthony C
Published: May 2004

Abstract  The Old World genus Panchaetothrips Bagnall has included five species, of which one is a pest of coffee in eastern Africa, and another attacks arrowroot, bananas and turmeric in India. The genus is here newly recorded from Australia, with P. timonii sp. n. found breeding on the leaves of Timonius timon (Rubiaceae) at Broome on the north‐western coast. Immature stages fed on younger leaves, and, when disturbed, older larvae exuded an anal droplet. Adults were found mainly on mature leaves, where they exhibited the typically defensive behaviour of raising their heavily spined abdominal apex over the head. The new species is described and a key provided to the six known species of Panchaetothrips, although the identity of two South‐east Asian species remains in doubt.
Entrapment of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) on glandular trichomes of Lycopersicon species
Authors: Simmons Aaron T , Gurr Geoff M , McGrath Des , Martin Peter M , Nicol Helen I
Published: May 2004

Abstract  Cotton bollworm, Helicoverpa armigera (Hübner), is a major pest of tomato (Lycopersicon esculentum) in Australia. Host‐plant resistance may prove an alternative to current control methods. The role of entrapment in glandular‐trichome‐induced mortality of H. armigera on Lycopersicon spp. has not previously been confirmed. Levels of entrapment and mortality on accessions of L. hirsutum and L. pennellii were compared with those on a L. esculentum control 24, 48 and 72 h after placement on leaflets with trichomes intact or with exudates removed. Accessions PI 127827 (L. hirsutum) and PI 473422 (L. pennellii) had a significantly greater number of neonates trapped after 24 and 48 h and dead after 72 h than did L. esculentum. Removal of trichome exudates significantly reduced effects on insects. A relationship between the density of type IV trichomes and the number of trapped neonates was established. Entrapment led to mortality of H. armigera, but levels were low, suggesting that entrapment alone offers scope to contribute only partially to resistance to H. armigera. The implications of these results in the selection of an accession for use in a breeding program for resistance to a range of arthropod pests are discussed.