bluuebunny/crossref_metadata_2025 huggingface dataset:
Noggin maintains pluripotency of human embryonic stem cells grown on Matrigel
Authors: Chaturvedi G. , Simone P. D. , Ain R. , Soares M. J. , Wolfe M. W.
Published: June 2009

Objective:  Spontaneous differentiation of human embryonic stem cell (hESC) cultures is a major concern in stem cell research. Physical removal of differentiated areas in a stem cell colony is the current approach used to keep the cultures in a pluripotent state for a prolonged period of time. All hESCs available for research require unidentified soluble factors secreted from feeder layers to maintain the undifferentiated state and pluripotency. Under experimental conditions, stem cells are grown on various matrices, the most commonly used being Matrigel.

Materials and Methods:  We propose an alternative method to prevent spontaneous differentiation of hESCs grown on Matrigel that uses low amounts of recombinant noggin. We make use of the porosity of Matrigel to serve as a matrix that traps noggin and gradually releases it into the culture to antagonize bone morphogenetic proteins (BMP). BMPs are known to initiate differentiation of hESCs and are either present in the conditioned medium or are secreted by hESCs themselves.

Results:  hESCs grown on Matrigel supplemented with noggin in conditioned medium from feeder layers (irradiated mouse embryonic fibroblasts) retained both normal karyotype and markers of hESC pluripotency for 14 days. In addition, these cultures were found to have increased cell proliferation of stem cells as compared to hESCs grown on Matrigel alone.

Conclusion:  Noggin can be utilized for short term prevention of spontaneous differentiation of stem cells grown on Matrigel.
A change in pituitary magnetic resonance imaging protocol detects ACTH‐secreting tumours in patients with previously negative results
Authors: Chowdhury Iffat N. , Sinaii Ninet , Oldfield Edward H. , Patronas Nicholas , Nieman Lynnette K.
Published: June 2009

Objective  While detection of pituitary tumours with magnetic resonance imaging (MRI) may reduce diagnostic costs and improve surgical outcomes for patients with Cushing’s disease, the optimal T1‐weighted spin‐echo (SE) MRI protocol remains unknown. We hypothesized that specific MR scanning parameters influence detection of corticotropinomas.

Design and patients  Between December 1997 and November 2004, 21 of 84 consecutive patients with Cushing’s disease had a falsely negative initial pituitary MRI study and a lesion identified subsequently at the National Institutes of Health Clinical Center. This study retrospectively reviewed and compared technical parameters used for the two pituitary T1‐weighted SE MRIs in 18 patients with available scans.

Measurements  Repetition time (TR)/echo times (TE), field of view (FOV), matrix size, magnetic field strength, slice thickness, use of gadolinium contrast and the time interval between studies were recorded.

Results  The MRI interscan interval was 5·4 ± 1·1 months. All scans used gadolinium, matrix sizes were similar and nearly all had 3‐mm thick slices. Parameters that differed between the NIH‐ and externally performed scans were: TR (400 ms vs. 492 ± 19 ms, P = 0·0002); TE (10·3 ± 0·5 vs. 17·2 ± 1·2 ms, P = 0·0003); FOV (12 × 12 cm vs.17 ± 0·6 × 18 ± 0·7 cm, P < 0·0001). Immunohistochemistry of tumours resected at transsphenoidal surgery confirmed all to be corticotropinomas.

Conclusions  Not all ‘T1‐weighted SE’ scans are equally accurate. MRI technique, particularly FOV and TR/TE value, influences results. We recommend that endocrinologists consider pituitary MRI parameters when interpreting the results.
Effects of marine reserve age on fish populations: a global meta‐analysis
Authors: Molloy Philip P. , McLean Ian B. , Côté Isabelle M.
Published: June 2009

1. Marine reserves are widely used for conservation and fisheries management. However, there is debate surrounding the speed of population recovery inside reserves and how recovery differs among species. Here, we determine how reserve effectiveness in enhancing fish density changes with reserve age. We also examine how the effects of protection vary between fished and non‐fished species and among species of different body sizes, which we use as a proxy for life history and ecology.

2. We meta‐analysed over 1000 ratios of fish densities (inside : outside reserves) taken from reserves of 1–26 years old from around the world.

3. Overall, older reserves were more effective than younger reserves, with fish densities increasing within reserves by ∼5% per annum relative to unprotected areas. Reserves older than 15 years consistently harboured more fish compared with unprotected areas; younger reserves were less reliably effective.

4. Large, fished species responded strongly and positively to protection in old (>15 years) and, unexpectedly, in new and young (≤10 years) reserves. Small, fished species and non‐fished species of all sizes showed weaker responses to protection that did not vary predictably with reserve age.

5. We expected large fish to respond more slowly to protection than smaller species. We also expected small species to decline after large fish had recovered (i.e. trophic cascades). Neither prediction was supported.

6. Synthesis and applications. Our meta‐analyses demonstrate that, globally, old reserves are more effective than young reserves at increasing fish densities. Our results imply that reserves should be maintained for up to 15 years following establishment, even if they initially appear ineffective. If protection is maintained for long enough, fish densities within reserves will recover and such benefits will be particularly pronounced for large, locally fished species.
Restraint and seclusion: a distressing treatment option?
Authors: MORAN A. , COCOMAN A. , SCOTT P. A. , MATTHEWS A. , STANIULIENE V. , VALIMAKI M.
Published: June 2009

The effectiveness of restraint and seclusion interventions in the nursing management of disturbed and aggressive clients remains questionable. Considerable debate continues regarding the use of these treatment options in psychiatric hospitals. The existing literature suggests that the controversial nature of restraint and seclusion creates a complex dilemma for nurses, which initiates emotional distress. This study specifically explored the emotions and feelings experienced by a group of psychiatric nurses working in Ireland in relation to incidents of restraint and seclusion. A qualitative research approach was employed incorporating focus group discussions. A total of 23 nurses participated in three focus group interviews. The data were analysed using qualitative interpretive analysis. Three themes were created consisting of: (1) the last resort – restraint and seclusion; (2) emotional distress; and (3) suppressing unpleasant emotions. It is suggested that the nurses' experience of restraint and seclusion created a dynamic movement between the release and suppression of distressing emotions. The oscillatory characteristics embedded within the nurses' emotional responses were reminiscent of a model of suffering developed by Morse in 2001. Consequently, this model is incorporated throughout the discussion of the findings to provide a more in‐depth description of the emotional distress experienced by the nurses in the study.
Correlations between Terasaki’s HLA class I epitopes and HLAMatchmaker‐defined eplets on HLA‐A, ‐B and ‐C antigens
Authors: Duquesnoy R. J. , Marrari M.
Published: June 2009

Although the determination of human leukocyte antigen (HLA) antibody specificity has traditionally been directed toward HLA antigens, there is now increasing attention to structurally defined HLA epitopes. An understanding of the HLA epitope repertoire is important to acceptable mismatching for sensitized patients and to a new epitope‐based matching algorithm aimed to reduce antibody‐mediated rejection. There are two strategies to determine the HLA epitope repertoire. Terasaki’s group has used an empirical method to analyze the reactivity of single allele Luminex panels with mouse monoclonal antibodies (mAbs) and absorbed/eluted alloantibodies with a computer program based on shared residues in the amino acid sequences of reactive alleles. HLAMatchmaker is a theoretical algorithm that predicts HLA epitopes on the HLA molecular surface from stereochemical modeling of epitope–paratope interfaces of antigen–antibody complexes. Our epitope repertoire is based on so‐called ‘eplets’ representing 3‐Å patches of at least one polymorphic residue on the molecular surface. A comparative analysis has shown that 81/103 Terasaki’s HLA class I epitopes are equivalent to individual eplets (n = 50) or pairs of eplets (n = 31) separated far enough to serve as potential contact sites for two complementarity‐determining regions of antibody. An additional 12 Terasaki’s epitopes (TerEps) correspond to eplets with permissible residue combinations that do not seem to affect epitope specificity. We could not identify corresponding eplets for the remaining 10 TerEps, including 8 that might be considered xeno‐epitopes defined by mouse mAbs. Conversely, HLAMatchmaker has 38 additional eplets in well‐exposed surface positions that do not have equivalent TerEps, and for many of them, we have found specific antibodies. These findings strengthen the concept that eplets are essential basic units of HLA epitopes and that they provide a better understanding of HLA immunogenicity (i.e. ability to induce an antibody response) and antigenicity (i.e. reactivity with specific antibody).
Living donor liver transplantation for hepatoblastoma with Beckwith–Wiedemann syndrome
Authors: Sasaki Kazunari , Kasahara Mureo , Fukuda Akinari , Shigeta Takanobu , Tanaka Hideaki , Nakagawa Satoshi , Mitsui Kazumasa , Harada Ryoko , Nakagawa Atsuko
Published: June 2009

Sasaki K, Kasahara M, Fukuda A, Shigeta T, Tanaka H, Nakagawa S, Mitsui K, Harada R, Nakagawa A. Living donor liver transplantation for hepatoblastoma with Beckwith–Wiedemann syndrome. Pediatr Transplantation 2010: 14:E89–E92. © 2009 John Wiley & Sons A/S.

Abstract:  BWS is one of the most well‐known somatic overgrowth syndromes, which is characterized by macroglossia, organomegaly, abdominal wall defects, and predisposition to embryonal tumors, such as Wilms’ tumor, hepatoblastoma, and adrenocortical carcinoma. We report a case of BWS in a girl with unresectable hepatoblastoma, who received a planned LVDT following neo‐adjuvant chemotherapy. This is the first case report of liver transplantation for patients with BWS. Tumor surveillance after transplantation would be necessary to detect possible recurrence of the original disease and development of other malignancies.
Anti‐IP1: Antibodies that Show an Association Between the I and P Blood Group Systems1
Authors: Issitt P. D. , Tegoli J. , Jackson Valerie , Sanders C. W. , Allen F. H.
Published: June 2009

Summary. In a study of four antibodies originally thought to be anti‐P1, two different specificities have been demonstrated. Anti‐P1 agglutinates P1 + bloods whether or not they are I +, while anti‐IP1 reacts with 1 + P1 + but not with I– P1+ cells. It appears that anti‐IP1 is directed not against the P1 antigen but against an antigenic determinant produced by the actions of both the P1 and I genes. Because bloods from newborn infants give weak or negative reactions with anti‐IP1, it is important that ‘anti‐P’ used for testing newborns be shown to be really anti‐P1 and not anti‐IP1.
The Relation of Some Antigenic Determinants of Immunoglobulin G to the Non‐L Chain Portion of the Fab Fragment
Authors: Wolf R. , Wulf B. , Deicher H.
Published: June 2009

Summary. This report confirms the fact that the Gm(f) group determinant is located on Fab but absent from Fc or isolated L chains. It also demonstrates that this specificity is not markedly effected by reduction, alkylation, and reconstitution of Fab. In addition, these studies show that Fab possesses antigenic determinants which are not related to isolated L chains or Fc. The relationship between the various antigenic determinants and the molecular structure of IgG is discussed.
No Beneficial Effect of Low‐Dose Fetal Intravenous Gammaglobulin Administration in Combination with Intravascular Transfusions in Severe Rh D Haemolytic Disease
Authors: Dooren Marion C. , van Kamp Inge L. , Scherpenisse Jan W. , Brand Ronald , Ouwchand Willem H. , Kanhai Humphrey H. H. , Engelfriet C. Paul , Gravenhorst Jack Bennebroek
Published: June 2009

Recent observations have shown that treatment with high‐dose intravenous gammaglobulin (IVIgG) given to the mother may improve fetal outcome in cases of severe Rh D alloimmunization. Unfortunately, the costs of this new method of treatment are too high for routine use. Therefore, we decided to apply this treatment to the fetus and to investigate whether the effect of IVIgG might be attributable to blockade of the fetal mononuclear phagocyte system. We have performed a randomized study in which 20 fetuses with severe Rh D‐haemolytic disease (HDN) were treated with intrauterine intravascular red cell transfusions (IUT). In 10 of these 20 cases transfusions were followed by administration to the fetus of low‐dose IVIgG (85.7 ± 11.6 mg/kg by ultrasound‐estimated fetal weight because of fetal vascular volume considerations). We compared the number of IUTs, postnatal exchange transfusions, haematocrit (Ht) and haemoglobulin (Hb) values before and after transfusion (s) needed by the newborns of the two groups. No significant differences in the transfusion requirements of the fetuses and in the clinical outcome could be demonstrated. However, the 95% confidence interval for the difference in the improvement of cord blood Ht was too wide for any conclusions. The 95% confidence interval for the difference in the improvement of Hb levels suggests that any clinically relevant advantage of IVIgG on Hb is unlikely.
Electrical Impedance Alterations of Red Blood Cells during Storage
Authors: Zhao Tian‐Xian , Shanwell Agneta
Published: June 2009

The electrical impedance of blood is determined mainly by the resistance of the plasma (Rp), resistance of the red cell interior fluid (Ri), and capacitance of the cell membranes (Cm). These parameters were measured on 10 stored blood samples consecutively during 4 or 5 weeks of storage at 4°C, once every week. Compared to the values of fresh samples, a statistically significant decrease in Rp was found mainly during the first week of storage, Ri did not decrease significantly until after 3 weeks, whereas Cm decreased progressively with time. These alterations can be explained by known red cell lesions during storage. The results indicate that electrical impedance measurements might be useful for monitoring red cell ageing and assessing the quality of stored red blood cells.
Quantitative Analysis of Lea and Leb Antigens in Human Saliva
Authors: Wang Baojie , Akiyama Kazuko , Kimura Hiroshi
Published: June 2009

We have measured the H type 1, Lea and Leb antigens in the saliva from 129 Japanese individuals by a time‐resolved europium ion fluorometric immunoassay using artificial antigen‐albumin complexes as the reference substances. We confirmed that the amount of Leb was larger than that of Lea in the saliva from secretors (Lea–b+) and vice versa in the saliva from nonsecretors (Lea+b–). Unexpectedly, we discovered appreciable amounts of Leb with small amounts of H type 1 in the saliva from the nonsecretors. The concentration of Leb was about 10, 6 and 35% of the concentration of the Lea in the saliva from the nonsecretors of the A, B and O groups, respectively. The possible formation of Leb from Lea, in addition to the formation of Leb from H type 1, in the salivary glands is discussed.
MAR, a Novel High‐Incidence Rh Antigen Revealing the Existence of an Allelic Sub‐System Including Cw (Rh8) and Cx (Rh9) with Exceptional Distribution in the Finnish Population
Authors: Sistonen Pertti , Sareneva Hannele , Pirkola Anna , Eklund Jarl
Published: June 2009

We present new genetic evidence obtained from population studies on Finns and from the studies on Finnish blood donors as well as their selected families using an antibody that defines a novel high‐incidence Rh antigen MAR. Anti‐MAR antibody shows an antithetical relationship to both anti‐Cw and anti‐Cx. The Rh antigens Cw (RH8) and, more strikingly, Cx (RH9) have each an exceptionally high frequency in Finns. Our studies on their genetic relationship indicate that the three antigens Cw, Cx and MAR behave as if being determined by alleles of the same Rh sub‐system. Furthermore, we conclude that this sub‐system manifests an inheritance pattern that is distinct from but analogous to that of the two well‐known allelic sub‐systems of C/c and E/e antigens.
Genetic diversity and population structure of wild and cultivated barley from West Asia and North Africa
Authors: Orabi J. , Jahoor A. , Backes G.
Published: June 2009

Population structure and relationships within and among 185 accessions of wild (Hordeum vulgare ssp. spontaneum) and cultivated barley (H. v. ssp. vulgare) from five countries in the West Asia and North Africa (WANA) region were studied using 36 simple sequence repeat (SSR) markers. The accessions were divided into subspecies/origin (S/O)‐groups and marker results were analysed in relation to genetic diversity and genetic structure. Wild barley from WANA was found to be highly diverse. The landraces from different countries of the Near East showed genetic diversity that was nearly as high as the wild barley from the same country. Further analyses showed that wild barley from Palestine/Israel represented the group with the highest diversity and the most complex structure. However, this group was distantly related to the cultivated barley in WANA, while the wild barley from the rest of the WANA region was closely related to the cultivated WANA barley. The high diversity and the close relationship to the wild barley make the WANA landraces an interesting genetic resource for both conservation and exploitation.
Angiomyolipomata: challenges, solutions, and future prospects based on over 100 cases treated
Authors: Sooriakumaran Prasanna , Gibbs Philippa , Coughlin Geoffrey , Attard Virginia , Elmslie Frances , Kingswood Christopher , Taylor Jeremy , Corbishley Cathy , Patel Uday , Anderson Christopher
Published: June 2009

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To examine the presentation, management and outcomes of patients with renal angiomyolipoma (AML) over a period of 10 years, at St George’s Hospital, London, UK.

PATIENTS AND METHODS

We assessed retrospectively 102 patients (median follow‐up 4 years) at our centre; 70 had tuberous sclerosis complex (TSC; median tumour size 3.5 cm) and the other 32 were sporadic (median tumour size 1.2 cm). Data were gathered from several sources, including radiology and clinical genetics databases. The 77 patients with stable disease were followed up with surveillance imaging, and 25 received interventions, some more than one. Indications for intervention included spontaneous life‐threatening haemorrhage, large AML (10–20 cm), pain and visceral compressive symptoms.

RESULTS

Selective arterial embolization (SAE) was performed in 19 patients; 10 received operative management and four had a radiofrequency ablation (RFA). SAE was effective in controlling haemorrhage from AMLs in the acute setting (six) but some patients required further intervention (four) and there was a significant complication rate. The reduction in tumour volume was only modest (28%). No complications occurred after surgery (median follow‐up 5.5 years) or RFA (median follow‐up 9 months). One patient was entered into a trial and treated with sirolimus (rapamycin).

CONCLUSIONS

The management of AML is both complex and challenging, especially in those with TSC, where tumours are usually larger and multiple. Although SAE was effective at controlling haemorrhage in the acute setting it was deemed to be of limited value in the longer term management of these tumours. Thus novel techniques such as focused ablation and pharmacological therapies including the use of anti‐angiogenic molecules and mTOR inhibitors, which might prove to be safer and equally effective, should be further explored.
External validation of a nomogram predicting mortality in patients with adrenocortical carcinoma
Authors: Zini Laurent , Capitanio Umberto , Jeldres Claudio , Lughezzani Giovanni , Sun Maxine , Shariat Shahrokh F. , Isbarn Hendrik , Arjane Philippe , Widmer Hugues , Perrotte Paul , Graefen Markus , Montorsi Francesco , Karakiewicz Pierre I.
Published: June 2009

OBJECTIVE

To develop nomograms predicting cancer‐specific and all‐cause mortality in patients managed with either surgery or no surgery for adrenocortical carcinoma (ACC).

PATIENTS AND METHODS

The models were developed in 205 patients with ACC and externally validated using 207 other patients with ACC, identified in the 1973–2004 Surveillance, Epidemiology and End Results database. The predictors comprised age, gender, race, stage and surgery status. Nomograms based on Cox regression model‐derived coefficients were used for predicting the cancer‐specific and all‐cause mortality, and were tested using area under the receiver operating characteristics (ROC) curve.

RESULTS

In cancer‐specific analyses, the median survival of patients within the development cohort was 26 months, vs 71 months in the external validation cohort (P < 0.001). In overall survival analyses, the median values were 21 vs 32 months for, respectively, the development and the external validation cohort (P < 0.001). Three variables (age, stage and surgical status) were included in the nomograms predicting cancer‐specific and all‐cause mortality. In the external validation cohort, the nomograms achieved between 72 and 80% accuracy for prediction of cancer‐specific or all‐cause mortality at 1–5 years after either surgery or diagnosis of ACC for non‐surgical patients.

CONCLUSION

Our models are the first standardized and individualized prognostic tools for patients with ACC. Their accuracy was confirmed within a large external population‐based cohort of patients with ACC.
The discrimination of dyslipidaemia using anthropometric measures in ethnically diverse populations of the Asia–Pacific Region: The Obesity in Asia Collaboration
Authors: Barzi F. , Woodward M. , Czernichow S. , Lee C. M. Y. , Kang J. H. , Janus E. , Lear S. , Patel A. , Caterson I. , Patel J. , Lam T. H. , Suriyawongpaisal P. , Huxley R.
Published: June 2009

Dyslipidaemia is a major risk factor for cardiovascular disease and is only detectable through blood testing, which may not be feasible in resource‐poor settings. As dyslipidaemia is commonly associated with excess weight, it may be possible to identify individuals with adverse lipid profiles using simple anthropometric measures. A total of 222 975 individuals from 18 studies were included as part of the Obesity in Asia Collaboration. Linear and logistic regression models were used to assess the association between measures of body size and dyslipidaemia. Body mass index, waist circumference, waist : hip ratio (WHR) and waist : height ratio were continuously associated with the lipid variables studied, but the relationships were consistently stronger for triglycerides and high‐density lipoprotein cholesterol. The associations were similar between Asians and non‐Asians, and no single anthropometric measure was superior at discriminating those individuals at increased risk of dyslipidaemia. WHR cut‐points of 0.8 in women and 0.9 in men were applicable across both Asians and non‐Asians for the discrimination of individuals with any form of dyslipidaemia. Measurement of central obesity may help to identify those individuals at increased risk of dyslipidaemia. WHR cut‐points of 0.8 for women and 0.9 for men are optimal for discriminating those individuals likely to have adverse lipid profiles and in need of further clinical assessment.
If you can't Beat them, Join them? Explaining Social Democratic Responses to the Challenge from the Populist Radical Right in Western Europe
Authors: Bale Tim , Green-Pedersen Christoffer , Krouwel AndréA , Luther Kurt Richard , Sitter Nick
Published: June 2009

Over the last three decades many Western European social democratic parties have been challenged by populist radical right parties. The growth and success of parties on the right flank of the party system represents a triple challenge to the social democrats: they increase the salience of issues traditionally ‘owned’ by the right; they appeal to working-class voters who traditionally support the centre left; and they may facilitate the formation of centre-right governments. This article explores social democratic parties’ strategic options in the face of this challenge, and tests the widespread assumption that the centre-left parties respond by taking a tougher stance on issues related to immigration and integration. Comparative analysis of developments in Austria, Denmark, the Netherlands and Norway reveals significant variation in the substance, scope and pace of the strategic responses of their social democratic parties. And it suggests that those responses are influenced not only by the far right but also by the reactions of mainstream centre-right parties and by parties on their left (and liberal) flank. Internal disunity, potential or actual, is also an important factor.
Kant's Argument for the Apperception Principle
Authors: Merritt Melissa McBay
Published: June 2009

Abstract: My aim is to reconstruct Kant's argument for the principle of the synthetic unity of apperception. I reconstruct Kant's argument in stages, first showing why thinking should be conceived as an activity of synthesis (as opposed to attention), and then showing why the unity or coherence of a subject's representations should depend upon an a priori synthesis. The guiding thread of my account is Kant's conception of enlightenment: as I suggest, the philosophy of mind advanced in the Deduction belongs to an enlightenment epistemology. Kant's conception of enlightenment turns on the requirement that a subject be able to recognize herself as the source of her cognitions. The argument for the apperception principle is reconstructed under the guidance of this conception of the ideal of enlightenment.
Mitochondrial membrane potential and apoptosis of blood mononuclear cells in untreated HIV‐1 infected patients
Authors: Sternfeld T , Tischleder A , Schuster M , Bogner JR
Published: June 2009

Objectives

Infection with HIV leads to progressive CD4 T‐cell loss, resulting in AIDS. Apoptosis is the main mechanism for the loss of infected and bystander cells, but the complex interacting factors inducing and inhibiting apoptosis are not fully understood. Mitochondrial dysfunction is a pivotal step of the apoptotic cascade and can result in reduced mitochondrial membrane potential.

Methods

The mitochondrial membrane potential of peripheral blood mononuclear cells (PBMC) was measured by flow cytometry using the dye JC‐1 (Molecular Probes Inc). Apoptotic cells were identified using the Annexin V assay (Becton Dickinson GmbH).

Results

The mitochondrial membrane potential of PBMC was significantly decreased and apoptotic cell rate was increased in HIV‐infected therapy‐naïve patients compared with HIV‐negative controls. There was a highly significant correlation between the mitochondrial membrane potential and the rate of apoptosis. CD4 cell count was correlated negatively to the apoptotic rate and positively to the mitochondrial membrane potential.

Conclusions

The JC‐1 assay is a sensitive tool to detect changes of mitochondrial membrane potential associated with apoptosis in HIV‐infected therapy‐naïve patients. We could show in vivo that a reduction of mitochondrial membrane potential is correlated to apoptosis of PBMC, CD4 cell count and HIV viral load during HIV infection.
Response of vitiligo to once‐ vs. twice‐daily topical tacrolimus: a controlled prospective, randomized, observer‐blinded trial
Authors: Radakovic S , Breier‐Maly J , Konschitzky R , Kittler H , Sator P , Hoenigsmann H , Tanew A
Published: June 2009

Background  A few studies on the treatment of vitiligo with topical tacrolimus have been published and showed promising results. However, most of these trials were uncontrolled.

Objective  This study aims to assess the response of vitiligo to once‐ or twice‐daily treatment with 0.1% tacrolimus in a controlled, randomized, observer‐blinded study.

Methods  Seventeen patients with generalized vitiligo were enrolled in this study. In each patient, two lesions were selected and randomized to treatment with either once‐ or twice‐daily application of 0.1% tacrolimus for a total period of 6 months. In 10 patients, a third patch was left untreated to serve as a control.

Results  Fifteen patients with 40 target lesions completed the study. Twice‐daily treatment induced excellent (> 75%) repigmentation in two lesions, moderate (> 25–50%) and poor (1–25%) repigmentation in four lesions each, and no response in five lesions. Once‐daily treatment resulted in moderate repigmentation in two lesions and poor repigmentation in five lesions, whereas no effect was observed in the remaining eight lesions. One out of 10 control lesions developed moderate spontaneous repigmentation, the other nine remained unchanged. Besides the frequency of tacrolimus application, the treatment outcome was determined by the localization of the affected areas with the facial region showing the best response.

Conclusions  Tacrolimus ointment appears to be an effective treatment option for facial vitiligo. A guarded prognosis is advisable for vitiliginous lesions on other localizations. Treatment must be applied twice daily for optimum response.

Conflict of Interest

None declared.
Sex differences and science: the etiology of science excellence
Authors: Haworth Claire M.A. , Dale Philip S. , Plomin Robert
Published: June 2009

Background:  Are there sex differences in the etiology of high performance in science in childhood that could contribute to the under‐representation of women in scientific careers? In this study the relative contributions of genetic and environmental influences on high performance in science in both boys and girls were assessed using standard twin analyses.

Methods:  The sample included 3000 twin pairs from the UK Twins Early Development Study (TEDS). Science performance ratings based on the UK National Curriculum were collected from teachers when the twins were 9, 10 and 12 years old. Science excellence was defined as performing above the 85th percentile. Sex‐limitation liability threshold models were used to assess sex differences in etiology.

Results:  We found no evidence for quantitative or qualitative sex differences in the etiology of science excellence, which was moderately heritable (30–50%), and influenced by both shared (40–56%) and non‐shared (10–13%) environmental influences.

Conclusions:  Although boys and girls do not differ genetically in relation to school science performance per se, the under‐representation of women in scientific careers may be due to attitudes rather than aptitudes.
Maternal sleep deprivation is a risk factor for small for gestational age: A cohort study
Authors: ABEYSENA Chrishantha , JAYAWARDANA Pushpa , DE A SENEVIRATNE Rohini
Published: June 2009

Aims: To determine trimester‐specific risk factors for small‐for‐gestational‐age (SGA) infants.

Methods: A population‐based prospective cohort study was conducted in Sri Lanka from May 2001 to April 2002. Pregnant women were recruited on or before 16 weeks of gestation and followed up until delivery. The sample size was 690. Trimester‐specific exposure status and potential confounding factors were gathered on average at 12th, 28th and 36th weeks of gestation. SGA was assessed using customised birth centile charts. Multiple logistic regression was applied, and the results were expressed as odds ratios (OR) and 95% confidence intervals (95%CI).

Results: The risk factors for SGA less than 5th centile were shift work and exposure to physical and chemical hazards during 2nd and 3rd trimesters (OR 4.20, 95%CI 1.10–16.0), sleeping for less than or equal to 8 h during 2nd or 3rd or both trimesters (OR 2.23, 95%CI 1.08–4.59), walking for less than or equal to 2.5 h per day (OR 2.66, 95%CI 1.12–6.31) and alcohol consumption during the 3rd trimester (OR 14.5, 95%CI 2.23–94.7). Poor weekly gestational weight gain was significantly associated with both SGA < 10th and < 5th centiles. None of the other factors became significant for SGA < 10th centile.

Conclusions: Risk factors for SGA less than 5th centile were sleep deprivation and shift work and exposure to physical and chemical hazards during 2nd and 3rd trimesters, less walking hours and alcohol consumption during 3rd trimester. Poor weekly gestational weight gain may be considered as a predictor of delivering an SGA infant.
Uterine papillary serous carcinoma: Patterns of failure and survival
Authors: WANG Wei , DO Viet , HOGG Russell , WAIN Gerard , BRAND Alison , BULL Colin , STENLAKE Annie , GEBSKI Val
Published: June 2009

Objective: To evaluate the outcome in patients with uterine papillary serous carcinoma (UPSC).

Methods: A retrospective review of women treated for UPSC between 1995 and 2006 in Westmead Hospital, Sydney. The patients were treated with total abdominal hysterectomy, bilateral salpingo‐oophorectomy and surgical staging. The majority of the patients had platinum‐based adjuvant chemotherapy and radiotherapy. Sites of initial recurrence were documented. Overall survival (OS) and progression free survival (PFS) were estimated using Kaplan–Meier method. Univariate and multivariate analysis was performed using Cox regression analysis to test the effects of multiple prognostic factors on survival.

Results: Two‐year and five‐year OS was 65% and 43%. The median OS was 39 months. Two‐year and five‐year PFS was 60% and 35%. Macroscopic residual disease at the completion of surgery was the only significant prognostic factor associated with worse OS on both univariate and multivariate analysis (P < 0.001). The median OS was only 11 months if patients had macroscopic residual disease, and all patients died within 18 months despite adjuvant therapies. Twenty‐one patients relapsed. The site(s) of initial recurrence were: vagina (five patients), pelvic lymph nodes (four patients), abdomen (11 patients), para‐aortic lymph nodes (six patients), inguinal lymph nodes (two patients) and distant metastases in seven patients. Only one of 16 patients who received vaginal brachytherapy failed in the vagina, but three of seven patients who received external beam pelvic radiotherapy failed in the vagina.

Conclusion: We recommend optimal cytoreduction surgery with the aim of leaving no macroscopic disease at the end of the operation. Vaginal brachytherapy should be considered as a component of adjuvant radiotherapy. Abdominal failure was the commonest mode of failure in our cohort of patients.
Do maternal‐ or pregnancy‐associated disease states affect blood pressure in the early neonatal period?
Authors: KENT Alison L. , SHADBOLT Bruce , HU Eric , MESKELL Sandra , FALK Michael C. , DAHLSTROM Jane E.
Published: June 2009

Background: Placental vascular changes associated with maternal disease states may affect fetal vascular development. There is evidence suggesting that being born prematurely is associated with a higher blood pressure (BP) in later life.

Aim: To determine whether maternal disease state affects BP in the early neonatal period.

Methods: Cohort study of neonates admitted to neonatal intensive care unit with exposure to maternal hypertension and diabetes. Inclusion criteria were neonates greater than 27 weeks gestation not ventilated or requiring inotropes for more than 24 h, materna l hypertension (pregnancy induced or essential) or diabetes of any kind requiring treatment, and spontaneous delivery. Exclusion criteria included chromosomal or congenital anomaly and illicit maternal drug use. Oscillometric BP measurements taken until discharge on days 1, 2, 3, 4, 7, 14, 21 and 28. Placental histopathology was performed.

Results: One hundred and ninety infants enrolled, 104 in the control and 86 in the study group. Sixty‐five infants were born between 28–31 weeks and 125 infants between 32–41 weeks gestation. Those born between 28–31 weeks with a history of diabetes had a statistically higher systolic, mean and diastolic BP throughout the first 28 days of life (P = 0.001; P = 0.007; P = 0.02). Those born between 32–41 weeks gestation with placental pathology associated with altered uteroplacental perfusion had a higher systolic BP (P = 0.005).

Conclusions: Maternal‐ or pregnancy‐associated disease states appear to influence BP in the early neonatal period. Diabetes and altered placental perfusion were associated with higher BP readings. Clinical significance of these statistically elevated BPs in the early neonatal period is unknown.
Maternal and neonatal outcomes following diabetes in pregnancy in Far North Queensland, Australia
Authors: DAVIS Bronwyn , BOND Dianne , HOWAT Paul , SINHA Ashim K , FALHAMMAR Henrik
Published: June 2009

Background: Diabetes in pregnancy (DIP) is increasing and is associated with a number of adverse consequences for both the mother and the child.

Aims: To compare local maternal and neonatal outcomes with state and national data.

Methods: Chart audit of all DIP delivered during 2004 at a regional teaching hospital and compare outcomes with national benchmark, Queensland and national Indigenous data.

Results: The local DIP frequency was 6.7%. The local compared to benchmark and state data demonstrated a higher frequency of Indigenous mothers (43.6% vs 6.8% vs 5.5%), caesarean sections (50.7% vs 26% vs 32.0%), hypoglycaemia (40.7% vs 19.5% vs 2.7%) and respiratory distress (16.6% vs 4.5% vs 2.3%) in infants, fewer normal birthweights (64.8% vs 82.6% vs 80.4%) and full‐term deliveries. More local mothers compared to benchmark had type 2 diabetes mellitus (T2DM) (15.4% vs 8.7%) but fewer used insulin (31.0% vs 46.6%); compared to state data, fewer women had gestational diabetes (79.5% vs 91.2%), however, insulin use was higher (22.8%). Furthermore, Aborigines had fewer pregnancies compared to Torres Strait Islanders (3.0 vs 5.0) and less insulin use (21.9% vs 59.3%) (P = 0.008–0.024). In contrast, non‐Indigenous versus Indigenous women showed fewer pregnancies, less T2DM (7.8% vs 23.7%), better glycaemic control, longer babies, more full‐term deliveries and less severe neonatal hypoglycaemia. Comparing local and national Indigenous data, local showed poorer outcomes, however, only 11.8% had diabetes or hypertension nationally.

Conclusion: The local cohort had poorer outcomes probably reflecting a more disadvantaged. Few differences were found between local Indigenous groups.
Obesity and Migraine: The Effect of Age, Gender and Adipose Tissue Distribution
Authors: Peterlin B. Lee , Rosso Andrea L. , Rapoport Alan M. , Scher Ann I.
Published: June 2009

(Headache 2010;50:52‐62)

Objective.— To evaluate the prevalence of migraine/severe headaches in those with and without general obesity and abdominal obesity (Abd‐O) and the effect of gender and age on this relationship.

Background.— General, or total body obesity (TBO), as estimated by body mass index, is a risk factor for migraine chronification. However, there are conflicting data as to whether TBO is associated with migraine prevalence. Abd‐O has been shown to be a better predictor of various disease states than TBO, but has not been evaluated in general population studies in association with migraine.

Methods.— Data from a general population survey, the National Health and Nutrition Examination Survey, were used to obtain demographics, self‐report of migraine/severe headaches and measured body mass indices, including height, weight, and waist circumference. All analyses were stratified by age and gender and multivariate analyses were determined through use of logistic regression models.

Results.— A total of 21,783 participants were included in the analysis. Between 20‐55 years of age, the prevalence of migraine was increased in both men and women with TBO as compared with those without, (P ≤ .001). Migraine was also more prevalent in those with Abd‐O as compared with those without (men: 20.1% vs 15.9%, P < .001; women: 36.9% vs 28.8.2%, P < .001). After 55 years of age, the prevalence of migraine in men was no longer associated with either TBO or Abd‐O. Similarly, after 55 years of age, the prevalence of migraine in women was no longer associated with TBO. However, in women older than 55 years, the prevalence of migraine was decreased in those with Abd‐O as compared with those without Abd‐O (14.4% vs 17.4%, P < .05). After adjusting for demographics, cardiovascular risk factors and Abd‐O, results were similar for the association between migraine prevalence and TBO in both younger and older men and women. After adjusting for demographics, cardiovascular risk factors and TBO, migraine prevalence was no longer associated with Abd‐O in younger men, but remained associated with an increased odds ratio of having migraine in younger women, as well as a decreased odds ratio in older women.

Conclusion.— The relationship between migraine and obesity varies by age, gender, and adipose tissue distribution (eg, TBO vs Abd‐O). In men and women ≤55 years old, migraine prevalence is increased in those with TBO, independent of Abd‐O. In addition, in men and women ≤55 years old, migraine prevalence is increased in those with Abd‐O; and in women this association is independent of TBO. In men older than 55 years, migraine is not associated with either TBO or Abd‐O. However, in women older than 55 years, migraine prevalence is decreased in those with Abd‐O and is independent of TBO.
The Relative Efficacy of Phenothiazines for the Treatment of Acute Migraine: A Meta‐Analysis
Authors: Kelly Anne‐Maree , Walcynski Tracy , Gunn Barry
Published: June 2009

Objective and Background.— Ranges of agents are used in the emergency departments to treat migraine headache. Some experts suggest that phenothiazines are among the most effective; clinical trials have been small with varied results. We performed a systematic review and meta‐analysis to determine the relative effectiveness of phenothiazines compared with placebo and other active agents for the treatment of acute migraine.

Methods.— We searched MEDLINE, EMBASE, CINAHL, Cochrane database, and international clinical trial registers for randomized controlled trials comparing parenteral phenothiazines with placebo or another active parenteral agent for treatment of acute migraine in adults. The primary outcome was relief of headache, and secondary outcome was clinical success. Analysis was for phenothiazines vs placebo, pooled other active agents, and metoclopramide for each outcome. Odds ratios (ORs) were calculated and pooled by using a random effects model (RevMan v5).

Results.— Thirteen trials were appropriate and had available data. Phenothiazines were compared with placebo in 5 trials and to another active agent in 10 (metoclopramide 4). Phenothiazine was more effective than placebo for headache relief (OR 15.02, 95% confidence interval [CI] 7.57‐29.82) and clinical success (OR 8.92, 95% CI 4.08‐19.51). Phenothiazines were more effective than other agents combined (OR 2.04, 95% CI 1.25‐3.31) and the metoclopramide subgroup (OR 2.25, 95% CI 1.29‐3.92) for clinical success, but no differences were found for headache relief. The clinical success rate of phenothiazines was 78% (95% CI 74‐82).

Conclusion.— Phenothiazines are more effective than placebo for the treatment of migraine headache and have higher rates of clinical success than other agents against which they have been compared.
Fast and reliable mutation detection of the complete exon 11–15 JAK2 coding region using non‐isotopic RNase cleavage assay (NIRCA)
Authors: Kambas Konstantinos , Mitroulis Ioannis , Kourtzelis Ioannis , Chrysanthopoulou Akrivi , Speletas Matthaios , Ritis Konstantinos
Published: June 2009

The screening for JAK2 V617F mutation in patients with polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis offers crucial information for the final diagnosis of these disorders. Recently, several JAK2 exons 12 and 14 mutations have been detected in V617F‐negative patients with idiopathic erythrocytosis. The need for a rapid and accurate assay for the mutation screening in both exons 12 and 14 prompted us for the application of a method for the analysis of the entire coding region between exons 11 and 15. We applied the non‐isotopic RNase cleavage assay and the accuracy of the method was verified in a series of V617F‐positive, V617F‐negative patients and healthy individuals, with no false results. This method can be applied in any laboratory without the requirement of specific sophisticated equipment.
Traumatic dental injuries in children with attention deficit/hyperactivity disorder
Authors: Avsar Aysun , Akbaş Seher , Ataibiş Tolga
Published: June 2009

Abstract – The aim of this study was to assess the frequency and distribution of traumatic injuries in 247 children with attention deficit/hyperactivity disorder (ADHD) who were 7–16 years old and attended the Ondokuz Mayıs University Medical Faculty (Department of Child Psychiatry, Samsun, Turkey). Each psychiatric diagnosis was based on criteria from the Diagnostic and Statistical Manual of Mental Disorders (4th edn, Washington, DC: American Psychiatric Association, 1994). Traumatic dental injuries were recorded using the classification of the World Health Organization, which was slightly modified by Andreasen and Andreasen (Textbook and color atlas of traumatic injuries, 3rd edn. Copenhagen, Denmark: Munksgaard; 1994. p. 151). Thirty‐two percent (78/247) of the ADHD children presented 103 traumatized teeth. The frequency of dental injuries peaked in children who were 10–12 years of age, and showed no significant difference between subtypes of ADHD or gender. The maxillary central incisors were the most vulnerable to injury, and there were no differences between the right and the left sides in terms of susceptibility. Uncomplicated crown fracture (52.4%) and complicated crown fracture (16.6%) were the most commonly encountered types of injury. The main causes of dental injury were falls, collisions with objects, violence, and traffic accidents, and there was no difference in the frequencies of these causes between subtypes of ADHD, age, or gender. Only 5.1% (4/78) of the ADHD children sought treatment within the first 24 h of the injury. In conclusion, children with ADHD experience dental injuries more frequently than was previously described.
Temporary management of permanent central incisors loss caused by trauma in primary dentition with natural crowns: a case report
Authors: Tüzüner Tamer , Kuşgöz Adem , Nur Bilge Gülsüm
Published: June 2009

Abstract –  Primary teeth injuries may cause developmental disturbances in the permanent dentition and loss of permanent incisors could be treated with different options. In this case report, an 11‐year‐old boy, with a history of trauma at the age of 4 years, is presented. Premature loss of permanent upper right central and upper left central teeth because of the mobility and arrest in root development were treated using patient’s own natural crowns on a removable appliance. This treatment option could be considered as an esthetic and functional temporary management of permanent central incisors loss until the definitive treatment will be completed in the future.