bluuebunny/crossref_metadata_2025 huggingface dataset:
The brachydactylies: a molecular disease family
Authors: Mundlos S
Published: September 2009

Brachydactyly refers to shortening of the hands and/or feet due to missing, deformed, or shortened bones. It may occur as an isolated trait or as part of a syndrome. According to their pattern of skeletal involvement, the isolated brachydactyly forms have been categorized in the groups A–D including several subgroups. As in many other genetic conditions, there is considerable phenotypic overlap between the groups. The identification of the molecular causes of these conditions has offered insights into their pathogenesis. The generation of animal models has facilitated research on the pathogenic events during digit development that lead to the brachydactyly phenotype. These studies have shown that the BMP pathway plays a pivotal role in the normal development of digits and joints and that the majority of brachydactyly disease genes are directly or indirectly linked to this pathway. Together, these genes function in a regulatory network which is deregulated in the disease state. As a consequence of the close interactions within the network, overlapping phenotypes are generated that are, nevertheless, characterized by specific recognizable patterns. This principle does not only apply for the brachydactylies but is also valid for many other disease entities. Groups of diseases that show a common phenotypic pattern due to the deregulation of a molecular network are suggested to be called molecular disease families.
Complete genomic sequence of a novel HLA‐B*1325 allele observed in a Chinese Han individual
Authors: Cheng L.‐H. , Jin S.‐Z. , Zhu W.‐G. , Li Z. , Zou H.‐Y.
Published: September 2009

The complete genomic sequence of HLA‐B*1325 allele shows one nucleotide difference from B*130101 at nt 302 where A → G resulting in an amino acid substitution from Asn(AAC) to Ser(AGC) at codon 77 in exon 2.
A new dipstick test (Allergodip®) for in vitro diagnosis of latex allergy – validation in patients with spina bifida
Authors: Niggemann Bodo , Wahn Ulrich
Published: September 2009

While there is established data on the value of various assays for determining specific immunoglobulin E (IgE) in serum, little has been reported about semi‐quantitative dipstick methods. Therefore, in a pilot study we compared a new dipstick assay (Allergodip®) with a well‐evaluated commercial assay (Pharmacia CAP‐system®), in terms of sensitivity and specificity, in sensitized and nonsensitized, symptomatic and non‐symptomatic patients with spina bifida. One‐hundred and thirty‐five patients with spina bifida (median age 10.8 years) were included in this study. Sixty‐nine patients (51.1%) were positive in the CAP‐system, 61 patients (45.2%) were positive in the Allergodip assay, and 67 patients (49.6%) were positive in a skin prick test with natural rubber latex milk. The concordance between the CAP‐system and Allergodip was good. Forty‐seven patients (34.8%) showed a positive response to the provocation test. The sensitivity of Allergodip was 85.1% compared with 91.5% for the CAP‐system. Specificity was 75.0% for the Allergodip assay and 70.5% for the CAP‐system. We conclude that the new dipstick test is a useful screening test for diagnosing sensitization to latex, e.g. when planning surgical interventions. However, in instances of doubtful reactions, discrepancies with clinical features or for scientific work it does not replace quantitative determination of specific IgE.
How the psychiatrists of a mental health department managed their patients before an attempted suicide
Authors: Scocco Paolo , Toffol Elena , Pilotto Elisa , Riccardo Pertile , Pavan Luigi
Published: September 2009

Aims:  The aim of this survey was to describe patients in care at a large mental health department in northern Italy who attempted suicide, and the clinical management adopted by their psychiatrists before the event.

Methods:  Data collection was based on a questionnaire administered to the reference psychiatrists.

Results:  Over a period of 12 months, 166 catchment area residents attempted suicide. Sixty‐six (40%) had contacted the mental health department in the previous two years and completed data were obtained on 63. Twenty‐nine (46%) suffered from mood, 26 (41%) from personality and 11 (18%) from schizophrenic disorders. Thirty‐four attempts occurred within one year of psychiatric ward discharge, mostly in the first quarter.

The reference psychiatrists reported that, at the last evaluation, 38 of 63 patients (60%) presented no change in clinical conditions, and 41 of 63 (68%) were considered at no immediate risk of suicide. Most of the attempted suicides in question (45, 72%) were judged to be unpreventable. In the two logistic regression analyses carried out, no independent variables were able to statistically significantly explain the variance in judged suicidal risk or the preventability of the index attempted suicide.

Conclusions:  According to the psychiatrists' descriptions of their last contact with the patients, most attempted suicides have not been preceded by a change in clinical conditions. Moreover, psychiatrists, irrespective of their age and gender, and of patient diagnosis, frequently judged the attempts to have been unpreventable.
Low level of parental bonding might be a risk factor among women with prolonged depression: A preliminary investigation
Authors: Handa Hiroko , Ito Akinori , Tsuda Hitoshi , Ohsawa Isao , Ogawa Toyoaki
Published: September 2009

Aims:  The aim of the present study was to determine whether or not the effect of parenting by the father and mother on outcomes for depression may be different between male and female subjects.

Methods:  A total of 115 patients were involved in this investigation: 74 had states of depression that continued for more than 2 years, and 41 had symptoms that remitted within 4 months. The Parental Bonding Instrument (PBI) was used to test for gender differences in the PBI score, the level of education, and the age at which the depression began, using an unpaired t‐test.

Results:  It is suggested that female patients with low paternal care and low levels of education have a higher likelihood of showing symptoms of prolonged depression in a primary episode. No relationship was found among prolongation of depression, educational level, and parental care in male patients. Furthermore, comparing the PBI quadrants established by Parker showed that female patients who were exposed to paternal care as ‘Affectionless Control’, had a tendency towards a higher risk of prolonged depression than female patients who received ‘Optimal Parenting’.

Conclusion:  Especially in female patients, the prolongation of depression is likely a result of low levels of paternal care and low education.
Zarit Caregiver Burden Interview: Development, reliability and validity of the Chinese version
Authors: Lu Lu , Wang Lie , Yang Xiaoshi , Feng Qiaolian
Published: September 2009

Aims:  To develop a specific scale used in measuring caregiver burden in China, and to evaluate its reliability and validity.

Methods:  Participants from the First and Second Affiliated Hospital of China Medical University and the Hospital of Tiefa Coal Industry Group completed the Chinese version of the Zarit Caregiver Burden Interview.

Results:  A total of 523 caregivers were included. The internal consistency of the Zarit Caregiver Burden Interview was high (Cronbach's α 0.875). The item–total correlations were all statistically significant (P < 0.01). Confirmatory factor analysis confirmed the five factors of the Zarit Caregiver Burden Interview in this study, and the goodness‐of‐fit indices reported for this 5‐factor model all fell within the acceptable range.

Conclusions:  The Chinese version of the Zarit Caregiver Burden Interview is reliable and valid for use. This study has important implications for burden measurement in Chinese caregivers.
Mucosal remodeling in long‐standing ulcerative colitis with colorectal neoplasia: Significant alterations of NCAM+ or α‐SMA+ subepithelial myofibroblasts and interstitial cells
Authors: Okayasu Isao , Yoshida Tsutomu , Mikami Tetuo , Hana Kiyomi , Yokozawa Masashi , Araki Kayo , Mitsuhashi Jun , Kikuchi Masaomi , Adachi Eijiro , Sada Miwa
Published: September 2009

Evidence has been provided in ulcerative colitis (UC) that early genomic instability of both epithelial and stromal cells is important for colorectal tumorigenesis, as well as remodeling and morphological alterations of mucosal crypts. To clarify roles of stromal cells in tumor development in UC, the present study focused on heterogeneous phenotypes of subepithelial myofibroblasts and interstitial cells, in association with mucosal remodeling. To clarify the relationship of alterations to tumorigenesis, mucosa of resected rectae from patients with UC (n= 49) and sporadic cancer (n= 10) were analyzed on immunohistochemistry and also on immunoelectron microscopy. Heterogeneous phenotypes of neural cell adhesion molecule (NCAM)+ and/or α‐smooth muscle actin (α‐SMA)+ subepithelial myofibroblasts and interstitial cells were demonstrated, corresponding to colonic stellate cells. Decrease of NCAM+ subepithelial myofibroblasts and interstitial cells, and increase of α‐SMA+ interstitial cells were significant in UC with neoplasia as compared to without neoplasia. α‐SMA+ muscularis mucosae was significantly more thickened in tumor cases. Deposits of Masson's trichrome+ and type III and I collagen in the muscularis mucosae and lamina propria appeared to increase in relation to the numbers of α‐SMA+ interstitial cells. Mucosal remodeling with alterations of NCAM+ or α‐SMA+ subepithelial and interstitial cells may play a critical role in UC‐associated tumorigenesis.
Lung cysts in Birt‐Hogg‐Dubé syndrome: Histopathological characteristics and aberrant sequence repeats
Authors: Koga Shunsuke , Furuya Mitsuko , Takahashi Yoko , Tanaka Reiko , Yamaguchi Atsushi , Yasufuku Kazuhiro , Hiroshima Kenzo , Kurihara Masatoshi , Yoshino Ichiro , Aoki Ichiro , Nakatani Yukio
Published: September 2009

Birt‐Hogg‐Dubé (BHD) syndrome is a rare disorder inherited in an autosomal dominant manner. The affected patients are predisposed to cutaneous fibrofolliculomas, renal cell tumors and lung cysts with recurrent pneumothorax. Contrary to neoplastic events in the skin and the kidney, the lung cysts have frequently been confused with non‐neoplastic changes such as blebs or bullae. Herein is reported a case of multiple lung cysts associated with BHD syndrome. Detailed histopathological characteristics of the lesion are also given. The lung cysts were closely associated with the peripheral interlobular septum, visceral pleura or septal‐pleural junctional region. These cysts were partly abutting alveolar structures, and lined by a layer of alveolar epithelium. These unique microscopic features supported the notion that the BHD lung lesions are distinct from other types of bullous changes. Genomic DNA analysis indicated an aberrant sequence repeat that caused frameshift mutation. Immunohistochemistry showed the localization of folliculin, the BHD gene‐encoding protein, in macrophages and epithelial cells in the patient's and normal control's lungs. Haploinsufficiency of folliculin may cause deranged alveolar development, leading to the aberrant cystic alveolar formation. The unique mutation patterns of abnormal sequence repeats in patients with BHD syndrome are also reviewed.
Small cell carcinoma with skeletal muscle differentiation of urinary bladder
Authors: Yajima Nobuhisa , Mizukami Hiroki , Wada Ryuichi , Saito Fumitada , Yagihashi Soroku
Published: September 2009

Reported herein is a case of small cell carcinoma (SCC) with skeletal muscle differentiation of urinary bladder in a 76‐year‐old woman presenting macrohematuria. Ultrasonography and CT detected a mass at the anterior wall of the urinary bladder, and total cystectomy followed. The tumor consisted of solid growth of small round cells with high nucleocytoplasmic ratio admixed with rhabdoid cells with eosinophilic cytoplasmic inclusions, invading the perivesical tissue. On immunohistochemistry the tumor cells were diffusely positive for neural markers and CD99, and sporadically for skeletal muscle markers. Fluorescence in situ hybridization showed no translocation of EWS. The patient died from massive recurrence in the pelvis 4 months after operation. This rare tumor indicates a potential of myoid differentiation in SCC of the urinary bladder and differential diagnosis from primitive neuroectodermal tumor is important because the treatment is different.
Association between masticatory performance and anthropometric measurements and nutritional status in the elderly
Authors: Okada Kiwako , Enoki Hiromi , Izawa Sachiko , Iguchi Akihisa , Kuzuya Masafumi
Published: September 2009

Aim:  The association between chewing ability and physical constitution and nutritional status remains uncertain in the elderly. We examined the relationships between chewing ability and anthropometric measurements or nutritional status in the elderly.

Methods:  A total of 200 subjects (78 men and 122 women; mean age ± standard deviation, 76.6 ± 7.1) were enrolled from geriatric clinical settings. Chewing ability was evaluated by color‐changeable chewing gum. Bodyweight, body mass index, mid‐upper‐arm circumference (MAC), and triceps skinfold, grip strength, serum albumin, physical and cognitive functions, depressive status, and dental status were determined.

Results:  Correlations were found between chewing ability and bodyweight, MAC, dental status, physical and cognitive functions, and depressive status after adjusting for age and sex. The concentrations of serum albumin were well‐correlated with chewing ability and anthropometric measurements. Stepwise linear regression analyses revealed that the masticatory cycle, dental status, bodyweight and MAC are predictors of chewing ability, and that age, chewing ability, grip strength and sex are predictors of serum albumin concentrations.

Conclusion:  Chewing ability is associated with not only oral health status but also the physical constitution of the elderly. In addition, chewing ability may add to the regulation of the nutritional status in the elderly.
The limbic circuitry underlying cocaine seeking encompasses the PPTg/LDT
Authors: Schmidt Heath D. , Famous Katie R. , Pierce R. C.
Published: September 2009

The direct glutamatergic projection from the medial prefrontal cortex (mPFC) to the nucleus accumbens plays a critical role in mediating the reinstatement of cocaine seeking behavior. The mPFC also sends glutamatergic projections to the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDT), which in turn send glutamatergic and cholinergic efferents to the ventral tegmental area (VTA) where they synapse on dopaminergic cells that innervate limbic structures including the nucleus accumbens. The goal of these experiments was to examine a potential role for the PPTg/LDT in the reinstatement of cocaine seeking. All rats were trained to self‐administer cocaine (0.25 mg, i.v.) on a fixed‐ratio 5 schedule of reinforcement. Cocaine self‐administration behavior was extinguished and a series of subsequent pharmacological experiments were performed to assess the potential role of the mPFC, PPTg/LDT and VTA in the reinstatement of cocaine seeking. Administration of the D1‐like dopamine receptor agonist SKF‐81297 (1.0 μg) directly into the mPFC produced a small, but statistically significant, increase in cocaine seeking behavior. Furthermore, microinjection of the ionotropic glutamate receptor antagonist CNQX (0.3 μg) into the PPTg/LDT attenuated the reinstatement of drug seeking induced by a priming injection of cocaine (10 mg/kg, i.p.). Intra‐VTA administration of CNQX, the nicotinic receptor antagonist mecamylamine (10.0 μg) or the muscarinic receptor antagonist scopolamine (24.0 μg) also blocked cocaine seeking. Taken together, these results suggest that cocaine priming‐induced reinstatement of drug seeking is mediated in part by a serial polysynaptic limbic subcircuit encompassing the mPFC, PPTg/LDT and VTA.
Influence of age on behavioral, immune and endocrine responses to the T‐cell superantigen staphylococcal enterotoxin A
Authors: Kohman Rachel A. , Crowell Beth , Urbach‐Ross Daniella , Kusnecov Alexander W.
Published: September 2009

Aged subjects are more vulnerable to administration of the endotoxin lipopolysaccharide, but research on age‐associated sensitivity to other immune stimulants has been limited. The current study examined the effects of administering the superantigen, staphylococcal enterotoxin A (SEA), to young (4‐month‐old) and aged (20‐month‐old) male C57BL/6J mice on consumption of a novel liquid, cytokine production, corticosterone levels, and expression of central mRNA levels of cytokines and corticotropin‐releasing hormone. SEA produced exaggerated hypophagia in aged mice, as they showed decreased consumption that persisted for 24 h. SEA increased hypothalamic mRNA levels of interleukin‐1β in the aged, but not the young, mice 2 h after administration. No differences in cytokine expression were observed 24 h after SEA. Both age groups showed increased plasma corticosterone levels 2 h after SEA administration. However, 24 h after SEA exposure the aged, but not the young, mice showed an augmented corticosterone response to the consumption test. Collectively, these data show that aging may exacerbate the behavioral and neuroinflammatory response to superantigen exposure. Further, the present study suggests that immune activation may result in delayed alterations in stress‐induced corticosterone production in aged subjects.
Aided speech‐identification performance in single‐talker competition by older adults with impaired hearing
Authors: HUMES LARRY E. , COUGHLIN MAUREEN
Published: September 2009

This study examined the effects of increased processing load on the closed‐set speech‐identification performance of young and older adults in a one‐talker background. Since the older adults had impaired hearing, speech‐identification performance was measured for spectrally shaped stimuli comparable to those experienced when wearing well‐fit hearing aids. There were three groups of listeners: (1) 19 older adults with high‐frequency sensorineural hearing loss; (2) 10 young adults with normal hearing who were assessed with the same spectrally shaped stimuli as the older adults; (3) 9 young adults with normal hearing who were assessed without spectral shaping and at a poorer target‐to‐competition ratio in an effort to equate overall performance to that of the older adults. In addition to this group factor, there were three within‐participant repeated‐measures independent variables designed to increase the demands on processing for the target and competing speech stimuli. These were: (1) competition meaningfulness (played in forward or reverse direction); (2) gender match between target and competing talkers (same or different gender); and (3) talker uncertainty (either the same target/competition talker pair or one of many such pairs on each trial). These three repeated‐measures independent variables were examined in a 2 × 2 × 2 factorial design. They showed roughly independent and additive effects on speech‐identification such that combinations of these variables decreased performance cumulatively. Older adults performed worse than young adults across the board, but also showed diminished relative improvement as the processing load was decreased. Individual differences in performance among the older adults were also examined.
Role of speechreading in audiovisual interactions during the recovery of speech comprehension in deaf adults with cochlear implants
Authors: STRELNIKOV K. , ROUGER J. , BARONE P. , DEGUINE O.
Published: September 2009

Speechreading is an important form of communicative activity that improves social adaptation in deaf adults. Cochlear implantation allows interaction between the visual speechreading abilities developed during deafness and the auditory sensory experiences acquired through use of the cochlear implant. Crude auditory information provided by the implant is analyzed in parallel with conjectural information from speechreading, thus creating new profiles of audiovisual integration with implications for brain plasticity. Understanding the peculiarities of change in speechreading after cochlear implantation may improve our understanding of brain plasticity and provide useful information for functional rehabilitation of implanted patients. In this article, we present a generalized review of our recent studies and indicate perspectives for further research in this domain.
Perspectives on multisensory experience and cognitive development in infants with cochlear implants
Authors: FAGAN MARY K. , PISONI DAVID B.
Published: September 2009

Infants learn about their environment through sensory exploration, acquiring knowledge that is important for cognitive development. However, little is known about the sensory exploration of infants with profound hearing loss before or after they receive cochlear implants. This paper reviews aspects of sensory perception and cognitive development in hearing infants, discusses the implications of delayed access to auditory information for multisensory perception and cognitive development in infants who use cochlear implants, and suggests several new directions for research addressing multisensory exploration and cognitive development in infants with cochlear implants.
The Signal‐Cognition interface: Interactions between degraded auditory signals and cognitive processes
Authors: STENFELT STEFAN , RÖNNBERG JERKER
Published: September 2009

A hearing loss leads to problems with speech perception; this is exacerbated when competing noise is present. The speech signal is recognized by the cognitive system of the listener; noise and distortion tax the cognitive system when interpreting it. The auditory system must interact with the cognitive system for optimal signal decoding. This article discusses this interaction between the signal and cognitive system based on two models: an auditory model describing signal transmission and degeneration due to a hearing loss and a cognitive model for Ease of Language Understanding. The signal distortion depends on the specifics of the hearing impairment and thus differently distorted signals can affect the cognitive system in different ways. Consequently, the severity of a hearing loss may not only depend on the lesion itself but also on the cognitive recourses required to interpret the signal.
The emergence of Cognitive Hearing Science
Authors: ARLINGER STIG , LUNNER THOMAS , LYXELL BJÖRN , KATHLEEN PICHORA‐FULLER M.
Published: September 2009

Cognitive Hearing Science or Auditory Cognitive Science is an emerging field of interdisciplinary research concerning the interactions between hearing and cognition. It follows a trend over the last half century for interdisciplinary fields to develop, beginning with Neuroscience, then Cognitive Science, then Cognitive Neuroscience, and then Cognitive Vision Science. A common theme is that an interdisciplinary approach is necessary to understand complex human behaviors, to develop technologies incorporating knowledge of these behaviors, and to find solutions for individuals with impairments that undermine typical behaviors. Accordingly, researchers in traditional academic disciplines, such as Psychology, Physiology, Linguistics, Philosophy, Anthropology, and Sociology benefit from collaborations with each other, and with researchers in Computer Science and Engineering working on the design of technologies, and with health professionals working with individuals who have impairments. The factors that triggered the emergence of Cognitive Hearing Science include the maturation of the component disciplines of Hearing Science and Cognitive Science, new opportunities to use complex digital signal‐processing to design technologies suited to performance in challenging everyday environments, and increasing social imperatives to help people whose communication problems span hearing and cognition. Cognitive Hearing Science is illustrated in research on three general topics: (1) language processing in challenging listening conditions; (2) use of auditory communication technologies or the visual modality to boost performance; (3) changes in performance with development, aging, and rehabilitative training. Future directions for modeling and the translation of research into practice are suggested.
Cognitive development, reading and prosodic skills in children with cochlear implants
Authors: LYXELL BJÖRN , WASS MALIN , SAHLÉN BIRGITTA , SAMUELSSON CHRISTINA , ASKER‐ÁRNASON LENA , IBERTSSON TINA , MÄKI‐TORKKO ELINA , LARSBY BIRGITTA , HÄLLGREN MATHIAS
Published: September 2009

This report summarizes some of the results of studies in our laboratory exploring the development of cognitive, reading and prosodic skills in children with cochlear implantation (CI). The children with CI performed at significantly lower levels than the hearing comparison group on the majority of cognitive tests, despite showing levels of nonverbal ability. The differences between children with CI and hearing children were most pronounced on tasks with relatively high phonological processing demands, but they were not limited to phonological processing. Impairment of receptive and productive prosody was also evident in children with CI. Despite these difficulties, 75% of the children with CI reached a level of reading skill comparable to that of hearing children. The results are discussed with respect to compensation strategies in reading.
Zn2+ mediates ischemia‐induced impairment of the ubiquitin‐proteasome system in the rat hippocampus
Authors: Chen Min , Chen Qian , Cheng Xue‐Wen , Lu Ting‐Jia , Liu Han‐Xing , Jia Jie‐Min , Zhang Chi , Xu Li , Xiong Zhi‐Qi
Published: September 2009

Deposition of ubiquitinated protein aggregates is a hallmark of neurodegeneration in both acute neural injuries, such as stroke, and chronic conditions, such as Parkinson’s disease, but the underlying mechanisms are poorly understood. In the present study, we examined the role of Zn2+ in ischemia‐induced impairment of the ubiquitin‐proteasome system in the CA1 region of rat hippocampus after transient global ischemia. We found that scavenging endogenous Zn2+ reduced ischemia‐induced ubiquitin conjugation and free ubiquitin depletion. Furthermore, exposure to zinc chloride increased ubiquitination and inhibited proteasomal enzyme activity in cultured hippocampal neurons in a concentration‐ and time‐dependent manner. Further studies of the underlying mechanisms showed that Zn2+‐induced ubiquitination required p38 activation. These findings indicate that alterations in Zn2+ homeostasis impair the protein degradation pathway.
The membrane cytoskeletal protein adducin is phosphorylated by protein kinase C in D1 neurons of the nucleus accumbens and dorsal striatum following cocaine administration
Authors: Lavaur Jérémie , Mineur Yann S. , Picciotto Marina R.
Published: September 2009

Repeated cocaine administration results in persistent changes in synaptic function in the mesolimbic dopamine system that are thought to be critical for the transition to addiction. Cytoskeletal rearrangement and actin dynamics are essential for this drug‐dependent plasticity. Cocaine administration increases levels of F‐actin in the nucleus accumbens and is associated with changes in the phosphorylation state of actin‐binding proteins. The adducins constitute a family of proteins that interact with actin and spectrin to maintain cellular architecture. The interaction of adducin with these cytoskeletal proteins is regulated by phosphorylation, and it is therefore expected that phosphorylation of adducin may be involved in morphological changes underlying synaptic responses to drugs of abuse including cocaine. In the current study, we characterized the regulation of adducin phosphorylation in the nucleus accumbens and dorsal striatum in response to various regimen of cocaine. Our results demonstrate that adducin is phosphorylated by protein kinase C in medium spiny neurons that express the dopamine D1 receptor. These data indicate that adducin phosphorylation is a signaling event regulated by cocaine administration and further suggest that adducin may be involved in remodeling of the neuronal cytoskeleton in response to cocaine administration.
The gastrointestinal effects that may follow the administration of theophylline reflect the pharmacodynamic profiles of both the parent drug and its metabolites
Authors: Psarra Theophano A. , Batzias Georgios C. , Peeters Theo L. , Koutsoviti‐Papadopoulou Maria
Published: September 2009

This study investigates the effect of theophylline along the rabbit gastrointestinal tract in comparison with the pharmacodynamic effect produced by the combined application of its three major metabolites. At concentrations up to 10−3 m, theophylline relaxed, in a declining order from the lower oesophageal sphincter (LOS) to pylorus, all regions of the upper gastrointestinal tract, but only the ascending colon from the intestinal regions studied. At concentrations higher than 10−3 m, instead of relaxing, theophylline strongly contracted the antrum and pylorus. In all three small intestinal regions, at concentrations up to 10−3 m, theophylline produced a weak contraction, which at higher concentrations became very strong, and at 10−2 mwas comparable to that produced by a supramaximal dose of acetylcholine. The additive relaxing effect resulting from the combined application of the theophylline’s metabolites was, from oesophagus to pylorus, weaker than that produced by theophylline, while on the ascending colon it was comparable to that of the parent drug. In contrast, the additive contractile effect of the metabolites on the three small intestinal regions was four to five times higher the one produced by theophylline. In conclusion, this study shows that the additive effect of the combined application of theophylline’s major metabolites on the rabbit gastrointestinal tract plays a major role in the final response of the intestine, and a minor one in the final responses of the gastric regions, while both the parent drug and the metabolites contribute to the final responses of the oesophagus and LOS.
Ribavirin therapeutic drug monitoring: why, when and how?
Authors: Stanke‐Labesque Françoise , Loustaud‐Ratti Véronique , Babany Gérard , Gagnieu Marie‐Claude , Marquet Pierre ,   The French Ribavirin Group OPTIRIB
Published: September 2009

Recent studies suggest the potential interest of ribavirin therapeutic drug monitoring to improve sustain virological response rate in hepatitis C virus‐infected patients. The present review details the pharmacokinetic properties of ribavirin, suggesting that it may be a good candidate for therapeutic drug monitoring, the different possible strategies and the analytical methods that could be employed.
Monitoring Change in Families Receiving Primary Mental Health Specialist Services: A Pragmatic Evaluation Within an Existing Service for the Under‐Fives
Authors: Pollock Jon , Horrocks Sue
Published: September 2009

Background:  Specialist CAMHS‐based services for pre‐school age children are being introduced in the UK using different models of care. The clinical value of these new services requires assessment.

Method:  Over 20 months a Primary Mental Health Specialist (Under 5s) service operating in South West UK was evaluated on a variety of themes including effectiveness. Recruited clients completed questionnaires on their own well‐being (on two occasions) and their child’s behaviour (on three occasions) over the intervention period.

Results:  Of the 67 carers assessed at or shortly after recruitment using the General Health Questionnaire, 55.2% were at high risk of having a clinically significant affective mental condition. Despite a trend towards improvement, neither the GHQ‐12 total score nor the proportion meeting the clinical criterion was statistically significantly reduced. The main index of child behaviour and emotional state demonstrated a statistically significant reduction in the number of disturbance‐indicating behaviours over the service intervention period. The largest changes occurred between recruitment and the 4th visit. Selection bias cannot be excluded.

Conclusions:  Significant changes determined over a relatively short period of intervention is consistent with an effect of service, but direct attribution demands care as no control groups were included.
The Impact of CHIP on Children's Insurance Coverage: An Analysis Using the National Survey of America's Families
Authors: Dubay Lisa , Kenney Genevieve
Published: September 2009

Objective. To assess the impact of the Children's Health Insurance Program (CHIP) on the distribution of health insurance coverage for low‐income children.

Data Source. The primary data for the study were from the 1997, 1999, and 2002 National Survey of America's Families (NSAF), which includes a total sample of 62,497 children across all 3 years, supplemented with data from other data sources.

Study Design. The study uses quasi‐experimental designs and tests the sensitivity of the results to using instrumental variable and difference‐in‐difference approaches. A detailed Medicaid and CHIP eligibility model was developed for this study. Balanced repeated replicate weights were used to account for the complex sample of the NSAF. Descriptive and multivariate analyses were conducted.

Principle Findings. The results varied depending on the approach utilized but indicated that the CHIP program led to significant increases in public coverage (14–20 percentage points); and declines in employer‐sponsored coverage (6–7 percentage points) and in uninsurance (7–12 percentage points). The estimated share of CHIP enrollment attributable to crowd‐out ranged from 33 to 44 percent. Smaller crowd‐out effects were found for Medicaid‐eligible children.

Conclusions. Implementation of the CHIP program resulted in large increases in public coverage with estimates of crowd‐out consistent with initial projections made by the Congressional Budget Office. This paper demonstrates that public health insurance expansions can lead to substantial reductions in uninsurance without causing a large‐scale erosion of employer coverage.
Racial and Ethnic Disparities in the Treatment of a Medicaid Population with Schizophrenia
Authors: Horvitz‐Lennon Marcela , McGuire Thomas G. , Alegria Margarita , Frank Richard G.
Published: September 2009

Objective. To assess health care disparities among black and Latino adults with schizophrenia receiving services during the period July 1994–June 2006, and to evaluate trends in observed disparities.

Data Sources. Administrative claims data from the Florida Medicaid program. Data sources included membership files (demographic information), medical claims (diagnostic, service, and expenditure information), and pharmacy claims (prescriptions used and expenditures).

Study Design. We identified adults with at least two schizophrenia claims during a fiscal year. We used generalized estimating equation models to estimate disparities in spending on psychotropic drugs, psychiatric inpatient services, all mental health services, and all health services.

Principal Findings. Spending on psychotropic drugs, mental health, and all health was 0.9–70 percent lower for blacks and Latinos than for whites. With the exception of blacks with substance use disorder comorbidity, minorities were less likely than whites to use psychiatric inpatient services. Psychiatric inpatient spending among users did not differ by race/ethnicity. With the exception of psychiatric inpatient utilization/spending, trend analyses showed no change or modest reductions in disparities.

Conclusions. Black and Latino Medicaid recipients diagnosed with schizophrenia experience health care disparities. Some but not all disparities narrowed modestly over the study period.
Role and Involvement of Life End Information Forum Physicians in Euthanasia and Other End‐of‐Life Care Decisions in Flanders, Belgium
Authors: Van Wesemael Yanna , Cohen Joachim , Onwuteaka‐Philipsen Bregje D. , Bilsen Johan , Distelmans Wim , Deliens Luc
Published: September 2009

Objective. To describe role and involvement of Life End Information Forum (LEIF) physicians in end‐of‐life care decisions and euthanasia in Flanders.

Study Design. All 132 LEIF physicians in Belgium received a questionnaire inquiring about their activities in the past year, and their end‐of‐life care training and experience.

Principal Findings. Response rate was 75 percent. Most respondents followed substantive training in end‐of‐life care. In 1 year, LEIF physicians were contacted 612 times for consultations in end‐of‐life decisions, of which 355 concerned euthanasia requests eventually resulting in 221 euthanasia cases. LEIF physicians also gave information about various end‐of‐life issues (including palliative care) to patients and colleagues.

Conclusions. LEIF physicians provide a forum for information and advice for physicians and patients. A similar health service providing support to physicians for all end‐of‐life decisions could also be beneficial for countries without a euthanasia law.
The Role of Monetary and Nonmonetary Incentives on the Choice of Practice Establishment: A Stated Preference Study of Young Physicians in Germany
Authors: Günther Oliver H. , Kürstein Beate , Riedel‐Heller Steffi G. , König Hans‐Helmut
Published: September 2009

Introduction. The study aimed to quantify the preferences of young physicians for different attributes relevant to practice establishment in Germany.

Methods. Qualitative in‐depth interviews of 22 physicians were conducted to identify relevant practice attributes. Based on this information, a questionnaire was developed containing a discrete choice experiment comprised of a “best–worst scaling” (BWS) task. It was mailed to a representative sample of 14,939 young physicians who were close to making a decision regarding practice establishment. Regression analysis was used to estimate utility weights quantifying physicians' preferences for practice attributes.

Results. Qualitative interviews identified six attributes: “professional cooperation,”“income,”“career opportunities of the partner,”“availability of child care,”“leisure activities,” and “on‐call duties.” For the BWS task, 5,026 returned questionnaires were analyzed. Results indicated that a change in income led to the largest utility change compared with changes in other attributes. Additional net income to compensate the disutility of a rural practice as compared with an urban practice was 9,044€/months (U.S.$ 11,938). Yet, nonmonetary attributes such as on‐site availability of childcare and fewer on‐call duties would decrease the additional income required to compensate the disutility of a rural practice.

Discussion. The results offer quantifiable information about young physicians' preferences in establishing a practice. It can assist health policy makers in developing tailored incentive‐based interventions addressing urban–rural inequalities in physician coverage.
Uterine perfusion following laparoscopic clipping of uterine arteries at myomectomy
Authors: ROSEN David M. B. , HAMANI Yaron , CARIO Gregory M. , CHOU Danny
Published: September 2009

Laparoscopic clipping of uterine arteries facilitates laparoscopic myomectomy with minimal blood loss. This paper shows the return to normal myometrial perfusion following this procedure with literary evidence of the safety and efficacy of this technique.
Cryotherapy as the treatment modality of postcoital bleeding: A randomised clinical trial of efficacy and safety
Authors: KONG Grace Wing Shan , YIM So Fan , CHEUNG Tak Hong , CHUNG Tony Kwok Hung
Published: September 2009

Background:  Postcoital bleeding is a common gynaecological problem that impacts on a woman's quality of life and sexual function. There is little systematic research into its management.

Aims:  To assess the efficacy and side‐effects of cryotherapy as treatment for postcoital bleeding.

Methods:  A prospective randomised controlled trial was conducted in a tertiary referral hospital in Hong Kong. A total of 85 women who presented with postcoital bleeding were recruited, and randomised to cryotherapy or no treatment. The treatment group received cryotherapy with compressed carbon dioxide through a cryoprobe placed on the cervix, and controls had cryoprobe on the cervix without compressed carbon dioxide flow. All recruited women were followed up two weeks, three months and six months to review their symptoms and response to the treatment.

Results:  The treatment group had a significantly better long‐term cure rate and improvement rate. At six months, the cryotherapy group reported a cure rate of 72.1% while that in the control group the cure rate was 50.0% (P = 0.04). The number needed to treat was 5. The mean improvement rate of the cryotherapy group was 82.88% ± 35.87 but was only 61.62% ± 55.30 in the control group (P = 0.04). The results were more significant in women with the defined pathological cervix. Apart from the vaginal discharge at second week follow up in the treatment group, there was no statistical significant difference in side‐effects and complications among two groups.

Conclusion:  Our study demonstrated that cryotherapy is a safe and an effective treatment for postcoital bleeding.
Fetal macrosomia and pregnancy outcomes
Authors: JU Hong , CHADHA Yogesh , DONOVAN Tim , O’ROURKE Peter
Published: September 2009

Background:  Pregnancies with a macrosomic fetus comprise a subgroup of high‐risk pregnancies. There is uncertainty in the clinical management and outcomes of such pregnancies.

Aim:  We sought to examine clinical management and maternal and fetal outcomes in pregnancies with macrosomic infants at Royal Brisbane and Women's Hospital (RBWH).

Methods:  Data from 276 macrosomic births (weighing ≥ 4500 g) and 294 controls (weighing 3250–3750 g) delivered during 2002–2004 at RBWH were collected from the hospital database. Univariate and logistic regression analyses were performed for maternal risk factors and maternal and neonatal outcomes that were associated with fetal macrosomia.

Results:  Macrosomia was more than two times likely in women with body mass index (BMI) of  > 30 kg/m2 (odds ratio (OR) 2.41, 95% confidence interval (CI) 1.26–4.61) and in male infant sex (OR 2.05, 95% CI 1.35–3.12), and four times more likely in gestation of > 40 weeks (OR 3.93, 95% CI 1.99–7.74). Maternal smoking reduced the risk of fetal macrosomia (OR 0.27, 95% CI 0.14–0.51).

Macrosomia was associated with nearly two times higher risk of emergency caesarean section (OR 1.75, 95% CI 1.02–2.97) and maternal hospital stay of > 3 days (OR 1.66, 95% CI 1.11–2.50), and four times higher risk of shoulder dystocia (OR 4.08, 95% CI 1.62–10.29). Macrosomic infants were twice as likely to have resuscitation (OR 2.21, 95% CI 1.46–3.34) and intensive care nursery admission (OR 1.89, 95% CI 1.03–3.46).

Conclusion:  Macrosomia was associated with an increased risk of adverse maternal and neonatal health outcomes. Optimal management strategies of macrosomic pregnancies need evaluation.
Castor oil for induction of labour: Not harmful, not helpful
Authors: BOEL Machteld Elisabeth , LEE Sue Jean , RIJKEN Marcus Johannes , PAW Moo Koo , PIMANPANARAK Mupawjay , TAN Saw Oo , SINGHASIVANON Pratap , NOSTEN François , McGREADY Rose
Published: September 2009

Background:  Castor oil is one of the most popular drugs for induction of labour in a non‐medical setting; however, published data on safety and effectiveness of this compound to induce labour remain sparse.

Aim:  To assess the safety and effectiveness of castor oil for induction of labour in pregnancies with an ultrasound estimated gestational at birth of more than 40 weeks.

Methods:  Data were extracted from hospital‐based records of all pregnant women who attended antenatal clinics on the Thai–Burmese border and who were more than 40 weeks pregnant. The effectiveness of castor oil to induce labour was expressed as time to birth and analysed with a Cox proportional hazards regression model. Measures associated with safety were fetal distress, meconium‐stained amniotic fluid, tachysystole of the uterus, uterine rupture, abnormal maternal blood pressure during labour, Apgar scores, neonatal resuscitation, stillbirth, post‐partum haemorrhage, severe diarrhoea and maternal death. Proportions were compared using Fisher's exact test.

Results:  Of 612 women with a gestation of more than 40 weeks, 205 received castor oil for induction and 407 did not. The time to birth was not significantly different between the two groups (hazard ratio 0.99 (95% confidence interval: 0.81 to 1.20; n = 509)). Castor oil use was not associated with any harmful effects on the mother or fetus.

Conclusions:  Castor oil for induction of labour had no effect on time to birth nor were there any harmful effects observed in this large series. Our findings leave no justification for recommending castor oil for this purpose.
The effect of elevated serum estradiol levels on the day of human chorionic gonadotropin injection on pregnancy outcomes in an assisted reproduction program
Authors: YOLDEMIR Tevfik , FRASER Ian S.
Published: September 2009

Background: Women who have a high estradiol level on the day of human chorionic gonadotropin injection are considered to have their in vitro fertilisation treatments compromised. How this really affects the pregnancy rates needs to be questioned.

Aim: To determine if elevated serum estradiol levels on the day of human chorionic gonadotropin injection have a deleterious effect on clinical and ongoing pregnancy rates in an assisted reproduction program.

Methods: A retrospective analysis was done of women with estradiol levels higher than 10 000 pmol/L and women with estradiol levels between 8000–10 000 pmol/L on the day of ovulation trigger undergoing in vitro fertilisation treatment at the Fertility Unit of the Royal Prince Alfred Hospital, University of Sydney, Australia. Pregnancy rates were compared for those having fresh embryo transfers and those having frozen thawed embryo transfers in subsequent cycles.

Results: There was no difference between the groups in terms of clinical and ongoing pregnancy rates.

Conclusion:  Frozen thawed embryos obtained from controlled ovarian hyperstimulation cycles resulted in similar clinical and ongoing pregnancy rates as those obtained in previous fresh embryo transfer cycles.
Diurnal changes and frequency dependence in male mating preference for female morphs in the damselfly Ischnura senegalensis (Rambur) (Odonata: Coenagrionidae)
Authors: TAKAHASHI Yuma , WATANABE Mamoru
Published: September 2009

Ischnura senegalensis females exhibit color dimorphism, consisting of an andromorph and a gynomorph, which might be maintained under a frequency‐dependent process of mating harassment by mate‐searching males. Males change their mating preference for female morph depending on prior copulation experience. Binary choice experiments between two female morphs were carried out in four local populations in the early morning (07.00–09.00 hours) and the afternoon (12.00–14.00 hours), times which mark the onset and the end of diurnal mating activity, respectively. According to the line census along the water's edge, the proportion of andromorphs in the female population varied from 21 to 67% throughout the survey period for four local populations. Males showed non‐biased preference for female morphs in the early morning in each local population, while they chose the common morph in the afternoon. Male mating preference for female morphs was positively correlated to the proportion of female morphs in the population. If the selective mating attacks on the common female morphs inhibit their foraging and/or oviposition behavior, frequency‐dependent male mating attacks might provide a selective force for maintaining the female color dimorphism in I. senegalensis.