bluuebunny/crossref_metadata_2025 huggingface dataset:
Bewilderment and conviction: the portrayal of madness in Ondaatje's Coming Through Slaughter
Authors: Polnay Adam
Published: November 2011

The scraps of historical data that exist about Buddy Bolden – a cornet player from New Orleans who influenced early jazz – have evoked curiosity in a wide range of writers, including psychiatrists. The latter are interested because Bolden ‘went berserk in a parade’ at the age of 29 and spent the rest of his life in an asylum. This article is about the novel Coming Through Slaughter by Michael Ondaatje, which is based on Bolden's life. I discuss how the form of the text – including its refusal to comment on where sense is lost – conveys to readers the bewilderment and conviction of Bolden's experience and allows them to share something of this.
Early intervention in psychosis: clinical aspects of treatment
Authors: Murphy Brendan P. , Brewer Warrick J.
Published: November 2011

Engaging patients in first-episode psychosis services is critical in maximising the effect of early intervention and establishing a framework for longer-term treatment. Biopsychosocial assessments determine a working diagnosis and inform evidence-based treatment. Atypical antipsychotics should be used at doses that maximise therapeutic benefit and adherence while minimising side-effects. Patients are helped to construct a narrative of their illness, including a shared understanding of the contribution of biological and environmental risks, and early warning signs. Common comorbid conditions, including depression, suicidal ideation, substance misuse and anxiety, should be addressed. Management of comorbid borderline and antisocial personality disorders is difficult; their nexus with psychosis is discussed. Cognitive–behavioural therapy is a mainstay of treatment, with specific interventions developed for problems typical in first-episode presentations. Core psychosocial interventions include psychoeducation, vocational and educational support, family interventions and multimodal group programmes.
Should early psychosis intervention be the focus for mental health services?
Authors: Castle David J.
Published: November 2011

This issue of Advances carries two articles from Melbourne, Australia, outlining the rationale for, and implementation of, early psychosis services. Their publication provides an opportunity to address some of the more contentious issues relating to the early psychosis intervention movement.
Persistent distress after psychological exposure to the Nagasaki atomic bomb explosion
Authors: Kim Yoshiharu , Tsutsumi Atsuro , Izutsu Takashi , Kawamura Noriyuki , Miyazaki Takao , Kikkawa Takehiko
Published: November 2011

Background

Although there is speculation that individuals living in the vicinity of nuclear disasters have persistent mental health deterioration due to psychological stress, few attempts have been made to examine this issue.

Aims

To determine whether having been in the vicinity of the Nagasaki atomic bomb explosion in the absence of substantial exposure to radiation affected the mental health of local inhabitants more than half a century later.

Method

Participants were randomly recruited from individuals who lived in the vicinity of the atomic bomb explosion in uncontaminated suburbs of Nagasaki. This sample (n = 347) was stratified by gender, age, perception of the explosion and current district of residence. Controls (n = 288) were recruited from among individuals who had moved into the area from outside Nagasaki 5–15 years after the bombing, matched for gender, age and district of residence. The primary outcome measure was the proportion of those at high risk of mental disorder based on the 28-item version of the General Health Questionnaire, with a cut-off point of 5/6. Other parameters related to individual perception of the explosion, health status, life events and habits were also assessed.

Results

Having been in the vicinity of the explosion was the most significant factor (OR = 5.26, 95% CI 2.56–11.11) contributing to poorer mental health; erroneous knowledge of radiological hazard showed a mild association. In the sample group, anxiety after learning of the potential radiological hazard was significantly correlated with poor mental health (P<0.05), whereas anxiety about the explosion, or the degree of perception of it, was not; 74.5% of the sample group believed erroneously that the flash of the explosion was synonymous with radiation.

Conclusions

Having been in the vicinity of the atomic bomb explosion without radiological exposure continued to be associated with poorer mental health more than half a century after the event. Fear on learning about the potential radiological hazard and lack of knowledge about radiological risk are responsible for this association.
Biogenetic explanations and public acceptance of mental illness: Systematic review of population studies
Authors: Angermeyer Matthias C. , Holzinger Anita , Carta Mauro G. , Schomerus Georg
Published: November 2011

Background

Biological or genetic models of mental illness are commonly expected to increase tolerance towards people with mental illness, by reducing notions of responsibility and blame.

Aims

To investigate whether biogenetic causal attributions of mental illness among the general public are associated with more tolerant attitudes, whether such attributions are related to lower perceptions of guilt and responsibility, to what extent notions of responsibility are associated with rejection of people who are mentally ill, and how prevalent notions of responsibility are among the general public with regard to different mental disorders.

Method

A systematic review was conducted of representative population studies examining attitudes towards people with mental illness and beliefs about such disorders.

Results

We identified 33 studies relevant to this review. Generally, biogenetic causal attributions were not associated with more tolerant attitudes; they were related to stronger rejection in most studies examining schizophrenia. No published study reported on associations of biogenetic causal attributions and perceived responsibility. The stereotype of self-responsibility was unrelated to rejection in most studies. Public images of mental disorder are generally dominated by the stereotypes of unpredictability and dangerousness, whereas responsibility is less relevant.

Conclusions

Biogenetic causal models are an inappropriate means of reducing rejection of people with mental illness.
Predicting the development of schizophrenia in high-risk populations: Systematic review of the predictive validity of prodromal criteria
Authors: Chuma Jefter , Mahadun Prem
Published: November 2011

Background

There is a great deal of debate on the usefulness and accuracy of prodromal criteria in predicting schizophrenia. The risk of treating people who screen false positive with medication is considerable. Yet intervening during the prodromal stage of illness may reduce the burden caused by schizophrenia.

Aims

To draw together the evidence base for the predictive validity of prodromal criteria in identifying individuals at high risk of developing schizophrenia.

Method

We conducted a systematic review of prospective studies investigating the predictive validity of prodromal criteria in schizophrenia.

Results

Our study found two main criteria, ultra-high-risk criteria and basic-symptoms criteria, used in studies investigating the predictive validity of prodromal symptoms. The sensitivity and specificity of ultra-high-risk criteria was 0.81 (95% CI 0.76–0.85) and 0.67 (95% CI 0.64–0.70) respectively and for basic-symptoms criteria sensitivity and specificity was 0.97 (95% CI 0.91–1.00) and 0.59 (95% CI 0.48–0.70) respectively.

Conclusions

Both ultra-high-risk criteria and basic-symptoms criteria are useful in predicting the development of schizophrenia among high-risk populations.
Overestimating patients' capacity
Authors: Lepping Peter
Published: November 2011

Clinicians regularly overestimate patients' capacity to make decisions. This may jeopardise their autonomous decision-making. It may lead to poor clinical outcomes for patients and has potential adverse legal consequences for clinicians. There is a need to use the legal principles of the Mental Capacity Act more rigorously.
Great wits and madness: More near allied?
Authors: Jamison Kay Redfield
Published: November 2011

A purported association between creativity and psychopathology is ancient, persistent and controversial. Biographical research, studies of living artists and writers, and investigations into the cognitive and temperamental factors linked to both creativity and mood disorders suggest a more specific link to bipolar illness. A new, large and well-designed population-based study adds further support to this connection.
Shame and acute psychiatric in-patient care
Authors: Crossley David Richard , Jones Alun Charles
Published: November 2011

Aims and method

To investigate the complementarities of staff and service users' experiences of shame in psychiatric in-patient settings. Qualitative methods were used by means of focus group interviews in two compositions – staff and service users. Data were transcribed and thematically analysed.

Results

Service user group transcripts revealed four prominent themes: ‘loss of value’, ‘loss of adulthood and autonomy’, ‘loss of subjectivity’ and ‘shaming or blaming of others’. Staff group transcripts also revealed two themes one of which overlapped with service users (‘shaming or blaming of others’) and one of which was distinct (‘entrapment’).

Clinical implications

Shame processes may be elicited by caregiving and impede treatment. Staff find themselves in the predicament of provoking the problems they intend to address. Suggestions are made as to how to respond to this dilemma and practically improve aspects of the in-patient care process to reduce shame.
Systematic review of workplace-based assessments in psychiatry: surgical dissection and recommendations for improvement
Authors: Sugand Kanchan , Palod Swapnil , Olua Kalu , Saha Satyajit , Naeem Asim , Matin Samina , Howlett Mary
Published: November 2011

Recent surveys have highlighted widespread criticisms of the use of workplace-based assessments (WPBAs) in psychiatric training. We describe our systematic review of psychiatric WPBAs, including a ‘surgical dissection’ of their format and process. From our review, we identified seven overarching WPBA themes, and have drawn on these to make further recommendations to strengthen the wider acceptability of WPBAs in psychiatric settings. We hope this will encourage further debate on ways of improving these tools, rather than them becoming side-lined as ‘top-down’ tick-box exercises.
‘From glorious to infamous’: the life span of (addiction) specialists in psychiatry
Authors: Swatkins Sandra , Gaston Romina Lopez , Hashmi Mahnaz , Thomas David
Published: November 2011

In this editorial we look at the implications of organisational changes to the National Health Service and financial constraints on addiction psychiatrists, and how creativity and adaptability could be the key to fostering survival and sustainability of subspecialties in danger of extinction.
Risk-Adapted Treatment in Clinical Stage I Testicular Seminoma: The Third Spanish Germ Cell Cancer Group Study
Authors: Aparicio Jorge , Maroto Pablo , del Muro Xavier García , Gumà Josep , Sánchez-Muñoz Alfonso , Margelí Mireia , Doménech Montserrat , Bastús Romá , Fernández Antonio , López-Brea Marta , Terrassa Josefa , Meana Andrés , del Prado Purificación Martínez , Sastre Javier , Satrústegui Juan J. , Gironés Regina , Robert Lidia , Germà José R.
Published: November 2011

Purpose

To confirm the efficacy of a risk-adapted treatment approach for patients with clinical stage I seminoma. The aim was to reduce both the risk of relapse and the proportion of patients receiving adjuvant chemotherapy while maintaining a high cure rate.

Patients and Methods

From 2004 to 2008, 227 patients were included after orchiectomy in a multicenter study. Eighty-four patients (37%) presented no local risk factors, 44 patients (19%) had tumors larger than 4 cm, 25 patients (11%) had rete testis involvement, and 74 patients (33%) had both criteria. Only the latter group received two courses of adjuvant carboplatin, whereas the rest were managed by surveillance.

Results

After a median follow-up time of 34 months, 16 relapses (7%) have been documented (15 [9.8%] among patients on surveillance and one [1.4%] among those treated with carboplatin). All relapses occurred in retroperitoneal lymph nodes, except for one case in pelvic nodes. Median node size was 25 mm, and median time to recurrence was 14 months. All patients were rendered disease-free with chemotherapy. The actuarial 3-year disease-free survival rate was 88.1% (95% CI, 82.3% to 93.9%) for patients on surveillance and 98.0% (95% CI, 94.0% to 100%) for those treated with adjuvant chemotherapy. Overall 3-year survival was 100%.

Conclusion

With the limitations of the short follow-up duration, we confirm that a risk-adapted approach is effective for stage I seminoma. Adjuvant carboplatin seems adequate treatment for patients with 2 risk criteria, as is active surveillance for those with 0 to one risk factors. More reliable predictive factors are needed to improve the applicability of this model.
Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer
Authors: Perez Edith A. , Suman Vera J. , Davidson Nancy E. , Gralow Julie R. , Kaufman Peter A. , Visscher Daniel W. , Chen Beiyun , Ingle James N. , Dakhil Shaker R. , Zujewski JoAnne , Moreno-Aspitia Alvaro , Pisansky Thomas M. , Jenkins Robert B.
Published: November 2011

Purpose

NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer.

Patients and Methods

Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS).

Results

Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis.

Conclusion

DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.
Microstome–macrostome transformation in the polymorphic ciliateTetrahymena voraxleads to mechanosensitivity associated with prey-capture behaviour
Authors: Grønlien Heidi K. , Hagen Bjarne , Sand Olav
Published: November 2011

Ciliates feed by phagocytosis. Some ciliate species, such as Tetrahymena vorax, are polymorphic, a strategy that provides more flexible food utilization. Cells of the microstomal morph of T. vorax feed on bacteria, organic particles and organic solutes in a non-selective manner, whereas macrostome cells are predators that consume specific prey ciliates. In the present study, we investigated a possible correlation between phagocytosis and mechanosensitivity in macrostome T. vorax. Microstome cells seem to be insensitive to mechanical stimulation whereas macrostome cells depolarise in response to mechanical stimulation of the anterior part of the cell. The amplitude of the receptor potential induced by either a prey ciliate or a 5 μm push by a glass needle was sufficient to elicit a regenerative Ca2+ spike. The difference in mechanosensitivity of the two forms correlates with the swimming behaviour when hitting an obstacle; microstome cells swim alongside the obstacle whereas macrostome cells swim backwards, turn and resume forward swimming. Macrostome cells prevented from backward swimming and the subsequent turn failed to capture prey cells in their pouch. Macrostome cells consumed heterospecific prey ciliates preferentially over conspecific microstome cells. This selectivity is not due to electrical membrane responses elicited by physical contact. Both microstome and macrostome cells accumulated in an area containing putative substances released from heterospecific prey ciliates, but the substances did not elicit any electrophysiological membrane responses. We conclude that the mechanosensitivity of macrostome cells is associated with the prey-capture behaviour, whereas the selective phagocytosis is probably due to chemo-attraction to heterospecific prey ciliates.
Leaky cell syndrome: a rare cause of pseudohyperkalaemia
Authors: Lukens Michaël V , de Mare Arjan , Kerbert-Dreteler Marjo J , van den Bergh Frank A
Published: November 2011

Life-threatening situations of hyperkalaemia are often caused by renal failure, hyperglycaemia or medication. However pseudohyperkalaemia, a falsely elevated potassium concentration, is usually caused by haemolysis, repeated clenching of the fist during venepuncture or abnormal cell numbers. Another rare cause of pseudohyperkalaemia is familial pseudohyperkalaemia, an autosomal dominantly inherited trait, with increased leakage of potassium from erythrocytes. Under normal in vivo conditions, this increased leakage is compensated by augmented activity of the Na+/K+ ATPase pump. However, after venepuncture the blood cools down to room temperature, reducing the activity of the Na+/K+ ATPase pump whereby the increased potassium leakage becomes more apparent. Here, we present a Dutch patient with extreme familial pseudohyperkalaemia. Interestingly, his two children also show increased potassium leakage at room temperature, albeit at a lower level. Despite the low prevalence of familial pseudohyperkalaemia, it can have important clinical implications and rapid recognition is desired.
Comparison of virtual bronchoscopy with fiberoptic bronchoscopy findings in patients exposed to sulfur mustard gas
Authors: Akhlaghpoor Shahram , Ahari Alireza Aziz , Shabestari Abbas Arjmand , Ghanei Mostafa , Ali Hamideh Ale , Shakiba Madjid
Published: November 2011

Background

Fiberoptic bronchoscopy (FB) is the best modality for evaluation of tracheobronchial endoluminal lesions. Virtual bronchoscopy (VB) with the aid of computed tomography (CT) makes it possible to reconstruct endoscopic-like visualization of major airways. Sulfur mustard (SM) used during the Iraq–Iran war affects respiratory tracts and can lead to tracheobronchial stenosis.

Purpose

To compare VB with FB in SM-exposed patients suspected for airway stenosis.

Material and Methods

Thirty-one patients were evaluated with CT and bronchoscopic studies about 15 years after chemical attacks. The median age of patients was 40 years. Spiral CT scans were obtained and data were transferred to a workstation to generate VB images of major airways. Less than one week after CT scan, FB was performed.

Results

For the tracheal pathologies seen in FB, the sensitivity, specificity, and accuracy of VB was 90.9%, 95%, and 93.5% for tracheal stenosis, 40%, 96.2%, and 87.1% for vocal cord problems, 100%, 100%, and 100% for postoperative changes, and 100%, 96.7%, and 96.8% for intratracheal nodule. The inflammation of mucosal surface could not be assessed by VB. The bronchial pathologies seen in FB included eight cases of stenosis, and one case of nodule. Sensitivity, specificity, and accuracy of VB for detection of bronchial stenosis was 62.5%, 97.8% and 92.6%, respectively. Overall sensitivity, specificity and accuracy of VB in detecting tracheobronchial stenosis were 78.9%, 97.0%, and 92.9%, respectively.

Conclusion

Our study indicates that VB is an accurate method for evaluating stenoses, endoluminal nodules, and poststenotic areas within the tracheobronchial tree of SM-exposed victims. This complementary method could be helpful in revealing hidden post-stenotic lesions and also better depict the long tracheal strictures and their actual length.
Factors affecting compliance in faecal occult blood testing: a cluster randomized study of the faecal immunochemical test versus the guaiac faecal occult test
Authors: Birkenfeld Shlomo , Belfer Rachel Gingold , Chared Miri , Vilkin Alex , Barchana Micha , Lifshitz Irena , Fruchter Dana , Aronski Dina , Balicer Ran , Niv Yaron , Levi Zohar
Published: November 2011

Objective

To compare the uptake of faecal immunochemical occult blood test (FIT) with guaiac faecal occult blood test (gFOBT) in a screening programme, with specific attention to the demographic and socioeconomic factors that might affect test uptake.

Setting

The Clalit Health Service screening programme, Israel.

Methods

Average-risk individuals aged 50–75 years were randomized into a FIT arm or gFOBT arm using a programme based on the socioeconomic status (SES) of their primary care clinics. G-FOBT was performed with Hemoccult SENSA™ (3 evacuations) and FIT with the OC- MICRO™ (3 evacuations, refrigerating mandated). The GLIMMIX model was used.

Results

There were 5,464 and 10,668 eligible participants in the FIT and gFOBT arms respectively. Compliance in taking the kits was better (but not statistically significantly better) with gFOBT (37.8% vs. 29.3%; odds ratio [OR] 1.43 [95% CI 0.73–2.80]; P = 0.227). Kit return was higher in the FIT arm (65.0% vs. 78.9%; OR 0.45 [95% CI 0.24–0.83], P = 0.021). Overall test uptake was affected by age, gender, being immigrant and SES (determined by whether or not the participant paid national insurance tax, and the SES of the primary care clinic). The overall uptake of gFOBT and FIT was comparable (OR 0.996 [95% CI 0.46–2.17], P = 0.99).

Conclusions

Overall compliance for test uptake was comparable between the two methods despite the more demanding procedure in the FIT arm. Sociodemographic parameters were the major determinants of compliance. An educational programme, with emphasis on the sociodemographic characteristics of the target population, should be instigated.
Direct mailing of faecal occult blood tests for colorectal cancer screening: a randomized population study from Central Italy
Authors: Rossi Paolo Giorgi , Grazzini Grazia , Anti Marcello , Baiocchi Diego , Barca Alessandra , Bellardini Paola , Brezzi Silvia , Camilloni Laura , Falini Patrizia , Maccallini Vincenzo , Mantellini Paola , Romeo Daniele , Rubeca Tiziana , Venditti Maria Antonietta
Published: November 2011

Background

Sending faecal occult blood tests (FOBT) by mail has been proposed both as a method to increase participation and a way to reduce staff costs in colorectal cancer screening.

Methods

Two multicentre randomized controlled trials (ISRCTN10351276) were performed: one randomly assigned 3196 individuals who had previously participated in colorectal screening to receive a FOBT kit at home or a standard invitation; in the second, 4219 people aged 50–69 years who did not respond to a screening invitation were either sent a FOBT or a standard recall letter. The cost per returned kit was calculated in each arm.

Results

Participation was higher with direct FOBT mailing in both trials: relative risk 1.11 (95% CI 1.06–1.17) and 1.36 (95% CI 1.16–1.60) for previous responders and non-responders, respectively. The cost per returned kit for previous responders ranged from 4.24€ to 16.10€, and from 3.29€ to 7.36€ with FOBT mailing and standard invitation, respectively, not including staff costs; for non-responders it ranged from 17.13€ to 46.80€, and from 7.36€ to 18.30€ with FOBT mailing and standard recall, respectively.

Conclusions

The FOBT mailing strategy modestly increased participation. This method can be used on a population of previous responders to reduce personnel costs and workload. When used as a reminder to non-responders, this method increases costs.
Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico
Authors: Vela-Amieva M , Ibarra-González I , Fernández-Lainez C , Monroy-Santoyo S , Guillén-López S , Belmont-Martínez L , Hernández-Montiel A
Published: November 2011

Objective

To expose causes leading to the delayed arrival of phenylketonuria (PKU) patients at a governmental reference centre (RC), and to describe their clinical characteristics.

Material and methods

PKU files registered during the past 18 years at the National Institute of Pediatrics in Mexico City were evaluated. Patients were classified into two groups according to their age at arrival: Group I (early reference), patients arriving during the first month of life; and Group II (late reference), those who arrived after thirty days of age. Time and causes of delay were documented.

Results

Of 57 recorded files, 10 were classified in Group I and 47 in Group II. Causes leading to the late arrival of Group II patients were absence of routine newborn screening (NBS), PKU not included in the routine NBS, sampling after the recommended age, false negative result, results without interpretation and/or instructions to follow, delayed notification of results, poor medical criteria of attending physician, difficulties in obtaining confirmatory tests, and administrative failures.

Conclusion

The main cause of late referral of PKU patients was the absence of PKU testing. As a developing country, Mexico still faces challenges in the proper functioning and expansion of the NBS programme. Most PKU patients arrived at the RC late, presenting with varying degrees of the clinical spectrum. Incorporating PKU testing into the already established Mexican NBS system and adding quality indicators to guarantee proper operation in all NBS phases is necessary to achieve the goal of identifying, referring, diagnosing, and treating patients promptly.
Claudins and Ki-67
Authors: Törzsök Péter , Riesz Péter , Kenessey István , Székely Eszter , Somorácz Áron , Nyirády Péter , Romics Imre , Schaff Zsuzsa , Lotz Gábor , Kiss András
Published: November 2011

Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins’ specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin-4, claudin-7, and Ki-67 might be used as potential markers to differentiate low-grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome.
Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas
Authors: Welander Jenny , Söderkvist Peter , Gimm Oliver
Published: November 2011

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors of the adrenal glands and the sympathetic and parasympathetic paraganglia. They can occur sporadically or as a part of different hereditary tumor syndromes. About 30% of PCCs and PGLs are currently believed to be caused by germline mutations and several novel susceptibility genes have recently been discovered. The clinical presentation, including localization, malignant potential, and age of onset, varies depending on the genetic background of the tumors. By reviewing more than 1700 reported cases of hereditary PCC and PGL, a thorough summary of the genetics and clinical features of these tumors is given, both as part of the classical syndromes such as multiple endocrine neoplasia type 2 (MEN2), von Hippel–Lindau disease, neurofibromatosis type 1, and succinate dehydrogenase-related PCC–PGL and within syndromes associated with a smaller fraction of PCCs/PGLs, such as Carney triad, Carney–Stratakis syndrome, and MEN1. The review also covers the most recently discovered susceptibility genes includingKIF1Bβ, EGLN1/PHD2, SDHAF2, TMEM127, SDHA, andMAX, as well as a comparison with the sporadic form. Further, the latest advances in elucidating the cellular pathways involved in PCC and PGL development are discussed in detail. Finally, an algorithm for genetic testing in patients with PCC and PGL is proposed.
Altitudinal Variation at Duplicated β-Globin Genes in Deer Mice: Effects of Selection, Recombination, and Gene Conversion
Authors: Storz Jay F , Natarajan Chandrasekhar , Cheviron Zachary A , Hoffmann Federico G , Kelly John K
Published: November 2011

Spatially varying selection on a given polymorphism is expected to produce a localized peak in the between-population component of nucleotide diversity, and theory suggests that the chromosomal extent of elevated differentiation may be enhanced in cases where tandemly linked genes contribute to fitness variation. An intriguing example is provided by the tandemly duplicated β-globin genes of deer mice (Peromyscus maniculatus), which contribute to adaptive differentiation in blood–oxygen affinity between high- and low-altitude populations. Remarkably, the two β-globin genes segregate the same pair of functionally distinct alleles due to a history of interparalog gene conversion and alleles of the same functional type are in perfect coupling-phase linkage disequilibrium (LD). Here we report a multilocus analysis of nucleotide polymorphism and LD in highland and lowland mice with different genetic backgrounds at the β-globin genes. The analysis of haplotype structure revealed a paradoxical pattern whereby perfect LD between the two β-globin paralogs (which are separated by 16.2 kb) is maintained in spite of the fact that LD within both paralogs decays to background levels over physical distances of less than 1 kb. The survey of nucleotide polymorphism revealed that elevated levels of altitudinal differentiation at each of the β-globin genes drop away quite rapidly in the external flanking regions (upstream of the 5′ paralog and downstream of the 3′ paralog), but the level of differentiation remains unexpectedly high across the intergenic region. Observed patterns of diversity and haplotype structure are difficult to reconcile with expectations of a two-locus selection model with multiplicative fitness.
Complex Population Dynamics and the Coalescent Under Neutrality
Authors: Volz Erik M
Published: November 2011

Estimates of the coalescent effective population size Ne can be poorly correlated with the true population size. The relationship between Ne and the population size is sensitive to the way in which birth and death rates vary over time. The problem of inference is exacerbated when the mechanisms underlying population dynamics are complex and depend on many parameters. In instances where nonparametric estimators of Ne such as the skyline struggle to reproduce the correct demographic history, model-based estimators that can draw on prior information about population size and growth rates may be more efficient. A coalescent model is developed for a large class of populations such that the demographic history is described by a deterministic nonlinear dynamical system of arbitrary dimension. This class of demographic model differs from those typically used in population genetics. Birth and death rates are not fixed, and no assumptions are made regarding the fraction of the population sampled. Furthermore, the population may be structured in such a way that gene copies reproduce both within and across demes. For this large class of models, it is shown how to derive the rate of coalescence, as well as the likelihood of a gene genealogy with heterochronous sampling and labeled taxa, and how to simulate a coalescent tree conditional on a complex demographic history. This theoretical framework encapsulates many of the models used by ecologists and epidemiologists and should facilitate the integration of population genetics with the study of mathematical population dynamics.
Sperm Development and Motility are Regulated by PP1 Phosphatases inCaenorhabditis elegans
Authors: Wu Jui-ching , Go Aiza C , Samson Mark , Cintra Thais , Mirsoian Susan , Wu Tammy F , Jow Margaret M , Routman Eric J , Chu Diana S
Published: November 2011

Sperm from different species have evolved distinctive motility structures, including tubulin-based flagella in mammals and major sperm protein (MSP)-based pseudopods in nematodes. Despite such divergence, we show that sperm-specific PP1 phosphatases, which are required for male fertility in mouse, function in multiple processes in the development and motility of Caenorhabditis elegans amoeboid sperm. We used live-imaging analysis to show the PP1 phosphatases GSP-3 and GSP-4 (GSP-3/4) are required to partition chromosomes during sperm meiosis. Postmeiosis, tracking fluorescently labeled sperm revealed that both male and hermaphrodite sperm lacking GSP-3/4 are immotile. Genetic and in vitro activation assays show lack of GSP-3/4 causes defects in pseudopod development and the rate of pseudopodial treadmilling. Further, GSP-3/4 are required for the localization dynamics of MSP. GSP-3/4 shift localization in concert with MSP from fibrous bodies that sequester MSP at the base of the pseudopod, where directed MSP disassembly facilitates pseudopod contraction. Consistent with a role for GSP-3/4 as a spatial regulator of MSP disassembly, MSP is mislocalized in sperm lacking GSP-3/4. Although a requirement for PP1 phosphatases in nematode and mammalian sperm suggests evolutionary conservation, we show PP1s have independently evolved sperm-specific paralogs in separate lineages. Thus PP1 phosphatases are highly adaptable and employed across a broad range of sexually reproducing species to regulate male fertility.
Update in Surfactant Therapy
Authors: Guttentag Susan , Foster Cherie D.
Published: November 2011

Exogenous surfactant is one of only a handful of neonatal therapies that has a strong evidence base, the product of countless basic and clinical studies over roughly 30 years between the first report of respiratory distress syndrome (RDS) as surfactant deficiency and the Food and Drug Administration (FDA) approval of the first surfactant preparation. Why then has surfactant therapy not succeeded in other neonatal, pediatric, or adult diseases associated with deficient or dysfunctional surfactant? By reflecting on the successes of surfactant therapy for RDS and examining critically the current evidence base for surfactant therapy in other neonatal pulmonary diseases, the authors chart a course for the future of surfactant therapy in neonatology.
Childhood Immunization: When Physicians and Parents Disagree
Authors: Gilmour Joan , Harrison Christine , Asadi Leyla , Cohen Michael H. , Vohra Sunita
Published: November 2011

Persistent fears about the safety and efficacy of vaccines, and whether immunization programs are still needed, have led a significant minority of parents to refuse vaccination. Are parents within their rights when refusing to consent to vaccination? How ought physicians respond? Focusing on routine childhood immunization, we consider the ethical, legal, and clinical issues raised by 3 aspects of parental vaccine refusal: (1) physician counseling; (2) parental decision-making; and (3) continuing the physician-patient relationship despite disagreement. We also suggest initiatives that could increase confidence in immunization programs.
Considering Complementary and Alternative Medicine Alternatives in Cases of Life-Threatening Illness: Applying the Best-Interests Test
Authors: Gilmour Joan , Harrison Christine , Asadi Leyla , Cohen Michael H. , Aung Steven , Vohra Sunita
Published: November 2011

In this article we explore decision-making about treatment when a child faces a life-threatening illness but conventional treatment presents substantial risk and uncertain benefit. When is it acceptable for parents to decide to use complementary and alternative medicine as an alternative, rather than a complement, to conventional care? We use the example of a young child suffering from progressive glycogen storage disease, for whom liver transplant offers the only prospect of a cure. Without a liver transplant, the disease usually results in death within a few years. However, experience using transplant to treat this illness has been limited, success is far from ensured, and the risks (including death and continued progression of the disease) are substantial. The child's parents, who are first-generation immigrants, consider the risks of the transplant unjustified because it still does not offer good prospects for a healthy future. They believe that traditional Chinese medicine could help remediate their daughter's disease. In the article we (1) review parents' obligation to make treatment decisions in the best interests of their child, (2) explain limits on parents' decision-making authority, (3) explore how “best interests” are determined, focusing on cases of serious illness for which conventional treatment is risky and benefit is possible but uncertain, (4) explain the standard of care that physicians must meet in advising about treatment, and (5) outline factors that clinicians and parents should take into account when making decisions.
Complementary and Alternative Medicine Practitioners' Standard of Care: Responsibilities to Patients and Parents
Authors: Gilmour Joan , Harrison Christine , Asadi Leyla , Cohen Michael H. , Vohra Sunita
Published: November 2011

In this article we explain (1) the standard of care that health care providers must meet and (2) how these principles apply to complementary and alternative medicine practitioners. The scenario describes a 14-year-old boy who is experiencing back pain and whose chiropractor performed spinal manipulation but did not recognize or take steps to rule out serious underlying disease—in this case, testicular cancer—either initially or when the patient's condition continued to deteriorate despite treatment. We use chiropractic care for a patient with a sore back as an example, because back pain is such a common problem and chiropracty is a common treatment chosen by both adult and pediatric patients. The scenario illustrates the responsibilities that complementary and alternative medicine practitioners owe patients/parents, the potential for liability when deficient care harms patients, and the importance of ample formal pediatric training for practitioners who treat pediatric patients.
Concluding Comments: Maximizing Good Patient Care and Minimizing Potential Liability When Considering Complementary and Alternative Medicine
Authors: Gilmour Joan , Harrison Christine , Vohra Sunita
Published: November 2011

Our goal for this supplemental issue of Pediatrics was to consider what practitioners, parents, patients, institutions, and policy-makers need to take into account to make good decisions about using complementary and alternative medicine (CAM) to treat children and to develop guidelines for appropriate use. We began by explaining underlying concepts and principles in ethical, legal, and clinical reasoning and then used case scenarios to explore how they apply and identify gaps that remain in practice and policy. In this concluding article, we review our major findings, summarize our recommendations, and suggest further research. We focus on several key areas: practitioner and patient/parent relationships; decision-making; dispute resolution; standards of practice; hospital/health facility policies; patient safety; education; and research. Ethical principles, standards, and rules applicable when making decisions about conventional care for children apply to decision-making about CAM as well. The same is true of legal reasoning. Although CAM use has seldom led to litigation, general legal principles relied on in cases involving conventional medical care provide the starting point for analysis. Similarly, with respect to clinical decision-making, clinicians are guided by clinical judgment and the best interests of their patient. Whether a therapy is CAM or conventional, clinicians must weigh the relative risks and benefits of therapeutic options and take into account their patient's values, beliefs, and preferences. Consequently, many of our observations apply to conventional and CAM care and to both adult and pediatric patients.
Substance Use Screening, Brief Intervention, and Referral to Treatment for Pediatricians
Authors: Levy Sharon J. L. , Kokotailo Patricia K. ,   Committee on Substance Abuse
Published: November 2011

This Policy Statement was revised. See https://doi.org/10.1542/peds.2016-1210.

As a component of comprehensive pediatric care, adolescents should receive appropriate guidance regarding substance use during routine clinical care. This statement addresses practitioner challenges posed by the spectrum of pediatric substance use and presents an algorithm-based approach to augment the pediatrician's confidence and abilities related to substance use screening, brief intervention, and referral to treatment in the primary care setting. Adolescents with addictions should be managed collaboratively (or comanaged) with child and adolescent mental health or addiction specialists. This statement reviews recommended referral guidelines that are based on established patient-treatment–matching criteria and the risk level for substance abuse.
Adolescents and HIV Infection: The Pediatrician's Role in Promoting Routine Testing
Authors: Emmanuel Patricia J. , Martinez Jaime ,   Committee on Pediatric AIDS
Published: November 2011

This Policy Statement was revised. See https://doi.org/10.1542/peds.2021-055207.

Pediatricians can play a key role in preventing and controlling HIV infection by promoting risk-reduction counseling and offering routine HIV testing to adolescent and young adult patients. Most sexually active youth do not feel that they are at risk of contracting HIV and have never been tested. Obtaining a sexual history and creating an atmosphere that promotes nonjudgmental risk counseling is a key component of the adolescent visit. In light of increasing numbers of people with HIV/AIDS and missed opportunities for HIV testing, the Centers for Disease Control and Prevention recommends universal and routine HIV testing for all patients seen in health care settings who are 13 to 64 years of age. There are advances in diagnostics and treatment that help support this recommendation. This policy statement reviews the epidemiologic data and recommends that routine screening be offered to all adolescents at least once by 16 to 18 years of age in health care settings when the prevalence of HIV in the patient population is more than 0.1%. In areas of lower community HIV prevalence, routine HIV testing is encouraged for all sexually active adolescents and those with other risk factors for HIV. This statement addresses many of the real and perceived barriers that pediatricians face in promoting routine HIV testing for their patients.
Ultrasonography in the diagnosis of ovarian and endometrial carcinoma
Authors: Valent Sándor , Oláh Orsolya , Sára Levente , Pajor Attila , Langmár Zoltán
Published: November 2011

Transvaginal sonography has become a crucial part of the routine gynecologic examination. It offers now a great help in the diagnosis of almost all gynecological diseases. Transvaginal ultrasound means the first step in the diagnosis of the first two most common gynecological malignancies, and in many cases we are able to set up a diagnosis of its own. The purpose of this article is to emphasize the significant role of transvaginal ultrasonography in the diagnosis of these two dieseases mentioned above, with summarizing the latest developments regarding the capabilities of sonography (Doppler-technique, three-dimensional ultrasonograpy). Orv. Hetil., 2011, 152, 1887–1893.
Tomato peel: rare cause of biliary tract obstruction
Authors: Hagymási Krisztina , Péter Zoltán , Csöregh Éva , Szabó Emese , Tulassay Zsolt
Published: November 2011

Foreign bodies in the biliary tree are rare causes of obstructive jaundice. Food bezoars are infrequent as well. They can cause biliary obstruction after biliary tract interventions, or in the presence of biliary-bowel fistula or duodenum diverticulum. Food bezoars usually pass the gastrointestinal tract without any symptoms, but they can cause abdominal pain and obstructive jaundice in the case of biliary tract obstruction. Endoscopic retrograde cholangio-pancreatography has the major role in the diagnosis and the treatment of the disease. Authors summarize the medical history of a 91-year-old female patient, who developed vomiting and right subcostal pain due to the presence of tomato peel within the ductus choledochus. Orv. Hetil., 2011, 152, 1907–1910.
Dental Fear in Children with a Cleft Lip and/or Cleft Palate
Authors: Vogels W.E.J.C. , Aartman I.H.A. , Veerkamp J.S.J.
Published: November 2011

Objective

To assess the level of dental fear in children with a cleft lip and/or palate, to compare this level with that of a normative group testing the hypothesis that children with a cleft lip and/or palate have a higher level of dental anxiety than children from the general population, and to assess the relation between dental fear and coping.

Design

Cross-sectional study.

Setting

VU Medical Centre University Amsterdam.

Patients

A total of 110 children (4 to 12 years old, 50 girls) with a cleft lip and/or palate.

Interventions

Dental fear in the study group was compared with a normative group of Dutch children.

Main Outcome Measures

Dental fear was investigated using the parental version of the dental subscale of the Children's Fear Survey Schedule for children aged 4 and 5 years old (n = 36). Also the Inventory of Stressful Situations was completed. Children aged 6 to 12 years old also completed the Dental Cope Questionnaire.

Results

Young children with a cleft lip and/or palate experience more dental fear compared with children in a normative control group (Children's Fear Survey Schedule dental subscale scores: 30.3 ± 14.6 compared with 24.6 ± 8.6, p < .01). A weak correlation was found between the child's dental anxiety (Children's Fear Survey Schedule dental subscale) and his or her coping behavior (Dental Coping Questionnaire) ( r = .196 p < .05). A clear correlation exists between the total Inventory of Stressful Situations and total Children's Fear Survey Schedule scores of the youngest age group ( r = .507 p < .01).

Conclusions

Findings support the hypothesis that dental anxiety is related to a higher level of exposure to medical interventions at a young age.