bluuebunny/crossref_metadata_2025 huggingface dataset:
There’s No Place Like Home: The Discursive Creation of Homelessness
Authors: Pascale Celine-Marie
Published: April 2005

In this article, the author examines the cultural production of homelessness in the United States, with particular concern for the intimate connection between discursive practices and material conditions. Drawing from poststructural discourse analysis, the author traces the discursive development of homelessness and homeless people between 1982 and 1996 in The New York Times, The Washington Post, and Los Angeles Times. The author explores changes in discursive practices and demonstrates how these changes produce, transform, and stabilize public knowledge about people who cannot afford housing. In conjunction, the author deconstructs current discursive practices in newspapers and examines the relationship of these practices to local political responses to homelessness. The author then discusses how discursive practices regarding poverty create particular problems, deliberations, and interventions while precluding others. Finally, the author considers the implications of the findings for class politics and social change.
Masquerade Performance and the Play of Sexual Identity in Calypso
Authors: Harewood Susan
Published: April 2005

This article examines the constitutive nature of Caribbean popular culture, specifically calypso performance, in postnational and postindependence identity formation. It seeks to contribute to research that highlights the importance of the work of the imagination in the active processes of community formations and intervene into standard calypso research and criticism that posits calypso as the voice of the people but identifies the people as a rigid, narrow, and bounded category. The article argues for full engagement with calypso within the context of carnival. It understands masquerade as a fundamental part of calypso performance and utilizes masquerade as an analytical category that permits us to understand the play of identities constituted within calypso performance. A masquerade analysis of The Mighty Gabby’s 2001 calypso competition finals performance exemplifies a case of a multivalent masquerade performance that specifically plays with discourses of sexual identity and provides clear insight into the aesthetic work of calypso.
Governing Doped Bodies: The World Anti-Doping Agency and the Global Culture of Surveillance
Authors: Park Jin-Kyung
Published: April 2005

This essay examines the governing practices of the World Anti-Doping Agency (WADA), an organization established in 1999 to cope with the crisis of illicit performance-enhancing drug use in international sport. The background, structure, and policies of WADA are analyzed while reflecting upon recent cultural studies debates on governmentality. In doing so, it is shown how WADA policies fundamentally work to police athletic bodies. Also demonstrated is that WADA embodies a First World, technology-driven governance of doping.
Visual Memory and Visual Perception Recruit Common Neural Substrates
Authors: Slotnick Scott D.
Published: April 2005

This human neuroimaging review aims to determine the degree to which visual memory evokes activity in neural regions that have been associated with visual perception. A visual perception framework is proposed to identify cortical regions associated with modality-specific processing (i.e., visual, auditory, motor, or olfactory), visual domain-specific processing (i.e., “what” versus “where,” or face versus visual context), and visual feature-specific processing (i.e., color, motion, or spatial location). Independent assessments of visual item memory studies and visual working memory studies revealed activity in the appropriate cortical regions associated with each of the three levels of visual perception processing. These results provide compelling evidence that visual memory and visual perception are associated with common neural substrates. Furthermore, as with visual perception, they support the view that visual memory is a constructive process, in which features or components from disparate cortical regions bind together to form a coherent whole.
Galanin and Cognition
Authors: Robinson John K.
Published: April 2005

Since the neuropeptide galanin’s discovery in 1983, information has accumulated that implicates it in a wide range of functions, including pain sensation, stress responses, appetite regulation, and learning and memory. This article reviews the evidence for specific functions of galanin in cognitive processes. Consistencies as well as gaps in the literature are organized around basic questions of methodology and theory. This review shows that although regularities are evident in the observed behavioral effects of galanin across several methods for measuring learning and memory, generalization from these findings is tempered with concerns about confounds and a restricted range of testing conditions. Furthermore, it is revealed that many noncognitive behavioral constructs that are relevant for assessing potential roles for galanin in cognition have not been thoroughly examined. The review concludes by laying out how future theory and experimental work can overcome these concerns and confidently define the nature of the association of galanin with particular cognitive constructs.
The Role of Attentional Bias in Substance Abuse
Authors: Robbins Steven J. , Ehrman Ronald N.
Published: April 2005

There has been much recent interest in the idea that drug users show biased attention toward drug-related events. Because drug stimuli produce conditioned responses that may motivate drug taking, biased attention toward these cues may play an important role in drug use and relapse following treatment. The performance of drug users on the Stroop task and visual dot-probe task has been interpreted as demonstrating attentional bias toward drug cues specific to an individual’s drug use history. However, studies often fail to include necessary control groups or comparison stimuli, thereby making it difficult to definitively conclude that reported results reflect a specific attentional response to personally relevant drug events. Although promising, these initial studies need to be followed up with better controlled demonstrations of attentional bias and with studies linking bias levels to other measures of drug taking.
Malignant Melanoma and Filariasis: A Coexistence or an Association?
Authors: Rekha A. , Ravi A. , Venu Nandigam , Shivanraj A.
Published: April 2005

Malignancy has been reported with chronic lymphedema, especially lymphangiosarcoma. The authors report on a patient with lymphedema due to filariasis, presenting with an ulcerated pigmented lesion that was malignant melanoma. A literature search revealed no previous report of such lesions existing together.
Accelerated telomere shortening in glycosylphosphatidylinositol (GPI)–negative compared with GPI-positive granulocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) detected by proaerolysin flow-FISH
Authors: Beier Fabian , Balabanov Stefan , Buckley Tom , Dietz Klaus , Hartmann Ulrike , Rojewski Markus , Kanz Lothar , Schrezenmeier Hubert , Brümmendorf Tim H.
Published: April 2005

Telomere length has been linked to disease stage and degree of (pan-)cytopenia in patients with bone marrow failure syndromes. The aim of the current study was to analyze the impact of replicative stress on telomere length in residual glycosylphosphatidylinositol-positive (GPI+) versus GPI– hematopoiesis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Peripheral blood granulocytes from 16 patients and 22 healthy individuals were analyzed. For this purpose, we developed proaerolysin flow-FISH, a novel methodology that combines proaerolysin staining (for GPI expression) with flow-FISH (for telomere length measurement). We found significantly shortened telomeres in GPI– granulocytes (mean ± SE: 6.26 ± 0.27 telomere fluorescence units [TFU]), both compared with their GPI+ counterparts (6.88 ± 0.38 TFU; P = .03) as well as with age-matched healthy individuals (7.73 ± 0.23 TFU; P < .001). Our findings are in support of a selective growth advantage model of PNH assuming that damage to the GPI+ hematopoietic stem-cell (HSC) compartment leads to compensatory hyperproliferation of residual GPI–HSCs.
Indole-3-carbinol suppresses NF-κB and IκBα kinase activation, causing inhibition of expression of NF-κB-regulated antiapoptotic and metastatic gene products and enhancement of apoptosis in myeloid and leukemia cells
Authors: Takada Yasunari , Andreeff Michael , Aggarwal Bharat B.
Published: April 2005

Indole-3-carbinol, found in Brassica species vegetables (such as cabbage, cauliflower, and brussels spouts), exhibits antitumor effects through poorly defined mechanisms. Because several genes that regulate apoptosis, proliferation, and metastasis are regulated by nuclear factor-κB (NF-κB), we postulated that indole-3-carbinol must mediate its activity through NF-κB modulation. We demonstrated that indole-3-carbinol suppressed constitutive NF-κB activation and activation induced by tumor necrosis factor (TNF), interleukin-1β (IL-1β), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and cigarette smoke; the suppression was not cell type specific, because activation was inhibited in myeloid, leukemia, and epithelial cells. This activation correlated with the sequential suppression of the IκBα kinase, IκBα phosphorylation, IκBα ubiquitination, IκBα degradation, p65 phosphorylation, p65 nuclear translocation, p65 acetylation, and NF-κB-dependent reporter gene expression. The NF-κB-regulated gene products cyclin D1, cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), survivin, inhibitor-of-apoptosis protein-1 (IAP1), IAP2, X chromosome-linked IAP (XIAP), Bcl-2, Bfl-1/A1, TNF receptor-associated factor-1 (TRAF1), and Fas-associated death domain protein-like interleukin-1β-converting enzyme inhibitory protein (FLIP) were all down-regulated by indole-3-carbinol. This down-regulation led to the potentiation of apoptosis induced by cytokines and chemotherapeutic agents. Indole-3-carbinol suppressed constitutive NF-κB activation in mononuclear cells derived from bone marrow of acute myelogenous leukemia patients, and this correlated with inhibition of cell growth. Overall, our results indicated that indole-3-carbinol inhibits NF-κB and NF-κB-regulated gene expression and that this mechanism may provide the molecular basis for its ability to suppress tumorigenesis. (Blood. 2005;106:641-649)
Molecular mechanism and functional implications of thrombin-mediated tyrosine phosphorylation of PKCδ in platelets
Authors: Murugappan Swaminathan , Shankar Haripriya , Bhamidipati Surya , Dorsam Robert T. , Jin Jianguo , Kunapuli Satya P.
Published: April 2005

Thrombin has been known to cause tyrosine phosphorylation of protein kinase C δ (PKCδ) in platelets, but the molecular mechanisms and function of this tyrosine phosphorylation is not known. In this study, we investigated the signaling pathways used by protease-activated receptors (PARs) to cause tyrosine phosphorylation of PKCδ and the role of this event in platelet function. PKCδ was tyrosine phosphorylated by either PAR1 or PAR4 in a concentration- and time-dependent manner in human platelets. In particular, the tyrosine 311 residue was phosphorylated downstream of PAR receptors. Also the tyrosine phosphorylation of PKCδ did not occur in Gαq-deficient mouse platelets and was inhibited in the presence of a phospholipase C (PLC) inhibitor U73122 and calcium chelator BAPTA (5,5′-dimethyl-bis(o-aminophenoxy)ethane-N, N, N ′, N ′-tetraacetic acid), suggesting a role for Gαq pathways and calcium in this event. Both PAR1 and PAR4 caused a time-dependent activation of Src (pp60c-src) tyrosine kinase and Src tyrosine kinase inhibitors completely blocked the tyrosine phosphorylation of PKCδ. Inhibition of tyrosine phosphorylation or the kinase activity of PKCδ dramatically blocked PAR-mediated thromboxane A2 generation. We conclude that thrombin causes tyrosine phosphorylation of PKCδ in a calcium- and Src-family kinase–dependent manner in platelets, with functional implications in thromboxane A2 generation.
ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-α-activated vascular endothelium under flow
Authors: Yang Lin , Froio Richard M. , Sciuto Tracey E. , Dvorak Ann M. , Alon Ronen , Luscinskas Francis W.
Published: April 2005

In vivo, leukocyte transendothelial migration (TEM) occurs at endothelial cell junctions (paracellular) and nonjunctional (transcellular) locations, whereas in vitro models report that TEM is mostly paracellular. The mechanisms that control the route of leukocyte TEM remain unknown. Here we tested the hypothesis that elevated intercellular adhesion molecule-1 (ICAM-1) expression regulates the location of polymorphonuclear leukocyte (PMN) TEM. We used an in vitro flow model of tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelium cells (HUVECs) or an HUVEC cell line transfected with ICAM-1GFP (green fluorescent protein) and live-cell fluorescence microscopy to quantify the location of PMN adhesion and TEM. We observed robust transcellular TEM with TNF-α-activated HUVECs and ICAM-1GFP immortalized HUVECS (iHUVECs). In contrast, primary CD3+ T lymphocytes exclusively used a paracellular route. Endothelial ICAM-1 was identified as essential for both paracellular and transcellular PMN transmigration, and interfering with ICAM-1 cytoplasmic tail function preferentially reduced transcellular TEM. We also found that ICAM-1 surface density and distribution as well as endothelial cell shape contributed to transcellular TEM. In summary, ICAM-1 promotes junctional and nonjunctional TEM across inflamed vascular endothelium via distinct cytoplasmic tail associations. (Blood. 2005;106:584-592)
Familial risk for non-Hodgkin lymphoma and other lymphoproliferative malignancies by histopathologic subtype: the Swedish Family-Cancer Database
Authors: Altieri Andrea , Bermejo Justo Lorenzo , Hemminki Kari
Published: April 2005

Non-Hodgkin lymphoma (NHL) consists of a heterogeneous group of tumors. Population-based data on the familial risk for specific histopathologic subtypes have not been established. Such data are useful for clinical counseling and for searching tumor subtypes sharing common genetic pathways. We used the Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for histopathology-specific subtypes of NHL in 4455 offspring with NHL whose parents or siblings were affected with different types of lymphoproliferative malignancies. A familial history of NHL significantly increased the risk for NHL (SIRparent = 1.8; SIRsibling = 1.9) and for diffuse large B-cell lymphoma (SIRparent = 2.3), follicular lymphoma (SIRsibling = 2.3), and B-cell lymphoma not otherwise specified (NOS) (SIRsibling = 3.4). For a parental history of histopathology-specific concordant cancer, the risks were significantly increased for diffuse large B-cell lymphoma (SIR = 11.8), follicular NHL (SIR = 6.1), plasma cell myeloma (SIR = 2.5), and chronic lymphocytic leukemia (SIR = 5.9). Familial clusters for NHL seemed stronger in females and in siblings. Our study provides the first quantification of the familial risks for NHL by histopathology. The present findings give evidence for a strong familial association of NHL, with little differences in the magnitude of risks for various histopathologic subtypes. The patterns of risks in parents and siblings support the hypothesis of an autosomal-dominant component for diffuse large B-cell NHL and a recessive one for follicular NHL. (Blood. 2005;106:668-672)
Zygotic nucleosome assembly protein–like 1 has a specific, non–cell autonomous role in hematopoiesis
Authors: Abu-Daya Anita , Steer Wendy M. , Trollope Alexandra F. , Friedeberg Christine E. , Patient Roger K. , Thorne Alan W. , Guille Matthew J.
Published: April 2005

Nucleosome assembly proteins (NAPs) bind core histones, facilitate chromatin remodeling, and can act as transcriptional coactivators. We previously described the isolation of a Xenopus NAP1-like (xNAP1L) cDNA, which encodes a member of this protein family. Its zygotic expression is restricted to neural cells, the outer cells of the ventral blood island (VBIs), and the ectoderm overlying the blood precursors. Here, we report that depletion of zygotic xNAP1L in embryos produces no obvious morphologic phenotype, but ablates α-globin mRNA expression in the VBIs. Transcript levels of the hematopoietic precursor genes SCL and Xaml (Runx-1) are also reduced in the VBIs. SCL expression can be rescued by injection of xNAP1L mRNA into the ectoderm, showing that the effect of xNAP1L can be non–cell autonomous. Fli1 and Hex, genes expressed in hemangioblasts but subsequently endothelial markers, were unaffected, suggesting that xNAP1L is required for the hematopoietic lineage specifically. Our data are consistent with a requirement for xNAP1L upstream of SCL, and injection of SCL mRNA into xNAP1L-depleted embryos rescues α-globin expression. Thus, xNAP1L, which belongs to a family of proteins previously believed to have general roles, has a specific function in hematopoiesis.
Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy
Authors: Greer Ian A. , Nelson-Piercy Catherine
Published: April 2005

To assess the safety and efficacy of low-molecular-weight heparins (LMWHs) for thromboprophylaxis and treatment of venous thromboembolism (VTE) in pregnancy, a systematic review of studies to the end of 2003 was undertaken. Data on VTE recurrence and side effects were extracted and cumulative incidences of VTE and adverse effects calculated. Of 81 reports identified, 64 reporting 2777 pregnancies were included. In 15 studies (174 patients) the indication for LMWH was treatment of acute VTE, and in 61 studies (2603 pregnancies) it was thromboprophylaxis or adverse pregnancy outcome. There were no maternal deaths. VTE and arterial thrombosis (associated with anti-phospholipid syndrome) were reported in 0.86% (95% confidence interval [CI], 0.55%-1.28%) and 0.50% (95% CI, 0.28%-0.84%) of pregnancies, respectively. Significant bleeding, generally associated with primary obstetric causes, occurred in 1.98% (95% CI, 1.50%-2.57%), allergic skin reactions in 1.80% (95% CI, 1.34%-2.37%), heparin-induced thrombocytopenia in 0%, thrombocytopenia (unrelated to LMWH) in 0.11% (95% CI, 0.02%-0.32%), and osteoporotic fracture in 0.04% (95% CI, < 0.01%-0.20%) of pregnancies. Overall, live births were reported in 94.7% of pregnancies, including 85.4% in those receiving LMWH for recurrent pregnancy loss. LMWH is both safe and effective to prevent or treat VTE in pregnancy.
Genotyping DNA pools on microarrays: Tackling the QTL problem of large samples and large numbers of SNPs
Authors: Meaburn Emma , Butcher Lee M , Liu Lin , Fernandes Cathy , Hansen Valerie , Al-Chalabi Ammar , Plomin Robert , Craig Ian , Schalkwyk Leonard C
Published: April 2005

Background

Quantitative trait locus (QTL) theory predicts that genetic influence on complex traits involves multiple genes of small effect size. To detect QTL associations of small effect size, large samples and systematic screens of thousands of DNA markers are required. An efficient solution is to genotype case and control DNA pools using SNP microarrays. We demonstrate that this is practical using DNA pools of 100 individuals.

Results

Using standard microarray protocols for the Affymetrix GeneChip® Mapping 10 K Array Xba 131, we show that relative allele signal (RAS) values provide a quantitative index of allele frequencies in pooled DNA that correlate 0.986 with allele frequencies for 104 SNPs that were genotyped individually for 100 individuals. The sensitivity of the assay was demonstrated empirically in a spiking experiment in which 15% and 20% of one individual's DNA was added to a DNA pool.

Conclusion

We conclude that this approach, which we call SNP-MaP (SNP m icroarrays a nd p ooling), is rapid, cost effective and promises to be a valuable initial screening method in the hunt for QTLs.
Angiotensinogen M235T gene variants and its association with essential hypertension and plasma renin activity in Malaysian subjects: A case control study
Authors: Say Yee-How , Ling King-Hwa , Duraisamy Gnanasothie , Isaac Suzanne , Rosli Rozita
Published: April 2005

Background

Essential hypertension is a major public health concern worldwide where its prevalence accounts for various cerebrovascular diseases. A common molecular variant of angiotensinogen (AGT), the precursor of potent vasoactive hormone angiotensin II, has been incriminated as a marker for genetic predisposition to essential hypertension in some ethnics. This case-control study was designed not only to determine the association of the AGT M235T gene variants with essential hypertension, but also its relationship to Plasma Renin Activity (PRA) in subjects attending the Health Clinic, Kuala Lumpur, Malaysia.

Methods

The study involved 188 subjects, 101 hypertensives and 87 normotensives. Consents were obtained from all the participated subjects. M235T gene variants were investigated using allele specific polymerase chain reaction and PRA was determined by radioimmunoassay. Hypertensinogenic factors such as dietary habits, physical activity, smoking and drinking habits were assessed using a pre-tested questionnaire.

Results

The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (χ2 = 23.184, P < 0.001 and χ2 = 21.482, P < 0.001, respectively). The odds ratio for hypertension was 1.36 (95% confidence interval 1.03–1.80) for subjects with homozygous mutated allele TT of the M235T variant compared with other genotypes or 1.98 (95% confidence interval 1.46–2.67) for those carrying T allele compared to those carrying M allele. Plasma Renin Activity is also significantly higher in hypertensive subjects (PRA = 3.8 ± 2.5 ngAI/ml/hr for hypertensives, PRA = 2.6 ± 1.3 ngAI/ml/hr for normotensives, P < 0.001), but was not significantly different between groups of genotypes (P = 0.118).

Conclusion

The M235T variant of the AGT is significantly associated with essential hypertension whereas the genotype TT or allele T is a possible genetic marker or risk factor for hypertension in Malaysian subjects.
Effects of glaucoma drugs on ocular hemodynamics in normal tension glaucoma: a randomized trial comparing bimatoprost and latanoprost with dorzolamide [ISRCTN18873428]
Authors: Zeitz Oliver , Matthiessen Eike T , Reuss Juliane , Wiermann Anne , Wagenfeld Lars , Galambos Peter , Richard Gisbert , Klemm Maren
Published: April 2005

Background

Reduced choroidal perfusion is hypothesized to play a role in the pathogenesis of normal tension glaucoma. Thus the impact of antiglaucomatous eye drops on ocular perfusion has been the focus of recent research and the subject of intensive investigations. The present study investigates whether topically applied latanoprost or bimatoprost influence ocular perfusion in patients with normal tension glaucoma and compares these effects with that changes detected after the treatment with dorzolamide.

Methods

Ocular hemodynamics were assessed by color Doppler imaging (CDI) shortly before and after a one-month treatment with either latanoprost, bimatoprost or dorzolamide. Primary end-points of the study were peak systolic and end-diastolic blood flow velocities in the short posterior ciliary artery (SPCA) under the new therapy. Intraocular pressure (IOP) and additional perfusion parameters in the SPCA and other retrobulbar vessels were tracked as observational parameters. n = 42 patients with normal tension glaucoma were enrolled in the study.

Results

Systolic and diastolic blood flow velocities in the SPCA showed no significant alteration after the treatment with latanoprost or bimatoprost. Dorzolamide lead to increase of peak systolic velocity. IOP was reduced by all three agents in a range reported in the literature.

Conclusion

Topically applied latanoprost and bimatoprost act in a hemodynamically neutral manner and have the capability to lower IOP even in patients with normal tension glaucoma and low initial IOP level. Dorzolamide accelerates blood flow in systole. None of the tested compounds has a negative impact on hemodynamics in the short posterior ciliary arteries.
Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review
Authors: Whiting Penny , Westwood Marie , Watt Ian , Cooper Julie , Kleijnen Jos
Published: April 2005

Background

Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture.

Methods

We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age.

Results

The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful.

Conclusion

Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation.
An exceptional Albanian family with seven children presenting with dysmorphic features and mental retardation: maternal phenylketonuria
Authors: Knerr Ina , Zschocke Johannes , Schellmoser Stefan , Topf Hans G , Weigel Corina , Dötsch Jörg , Rascher Wolfgang
Published: April 2005

Background

Phenylketonuria is an inborn error of amino acid metabolism which can cause severe damage to the patient or, in the case of maternal phenylketonuria, to the foetus. The maternal phenylketonuria syndrome is caused by high blood phenylalanine concentrations during pregnancy and presents with serious foetal anomalies, especially congenital heart disease, microcephaly and mental retardation.

Case presentation

We report on an affected Albanian woman and her seven children. The mother is affected by phenylketonuria and is a compound heterozygote for two pathogenetic mutations, L48S and P281L. The diagnosis was only made in the context of her children, all of whom have at least one severe organic malformation. The first child, 17 years old, has a double-chambered right ventricle, vertebral malformations and epilepsy. She is also mentally retarded, microcephalic, exhibits facial dysmorphies and small stature. The second child, a girl 15 years of age, has severe mental retardation with microcephaly, small stature and various dysmorphic features. The next sibling, a boy, died of tetralogy of Fallot at the age of three months. He also had multiple vertebral and rib malformations. The subsequent girl, now eleven years old, has mental retardation, microcephaly and epilepsy along with facial dysmorphy, partial deafness and short stature. The eight-year-old child is slightly mentally retarded and microcephalic. A five-year-old boy was a premature, dystrophic baby and exhibits mental retardation, dysmorphic facial features, brachydactyly and clinodactyly of the fifth finger on both hands. Following a miscarriage, our index case, the youngest child at two years of age, is microcephalic and mentally retarded and shows minor facial anomalies. All children exhibit features of phenylalanine embryopathy caused by maternal phenylketonuria because the mother had not been diagnosed earlier and, therefore, never received any diet.

Conclusion

This is the largest family suffering from maternal phenylketonuria reported in the literature. Maternal phenylketonuria remains a challenge, especially in woman from countries without a neonatal screening program. Therefore, it is mandatory to be alert for the possibility of maternal phenylketonuria syndrome in case of a child with the clinical features described here to prevent foetal damage in subsequent siblings.
You might as well smoke; the misleading and harmful public message about smokeless tobacco
Authors: Phillips Carl V , Wang Constance , Guenzel Brian
Published: April 2005

Background

Compared to smoking cigarettes, use of Western smokeless tobacco (ST) products is associated with a very small risk of life-threatening disease (with estimates in the range of a few percent of the risk from smoking, or even less). This means that smokers can realize substantial health benefits by switching to ST, an obvious substitute. But consumers and policy makers have little chance of learning that ST is much less dangerous than smoking because popular information provided by experts and advocates overstates the health risks from ST relative to cigarettes.

Methods

To examine the extent of this overstatement in one medium, we conducted a systematic review of websites containing information about ST and health risks. We examined the content of 316 relevant websites identified by a Google search.

Results

We found that when any substantive information about the risk from ST is given, the risk is almost universally conflated with the risk from cigarettes. Accurate comparative risk information was quite rare, provided by only a handful of websites, all appearing low in our search results (i.e., of low popularity and thus unlikely to be found by someone searching for information). About 1/3 of the websites, including various authoritative entities, explicitly claimed that ST is as bad as or worse than cigarettes. Most of the other sites made statements that imply the risks are comparable.

Conclusion

Through these websites, and presumably other information provided by the same government, advocacy, and educational organizations, ST users are told, in effect, that they might as well switch to smoking if they like it a bit more. Smokers and policy makers are told there is no potential for harm reduction. These messages are clearly false and likely harmful, representing violations of ethical standards.
Mid-term Body Mass Index increase among obese and non-obese individuals in middle life and deprivation status: A cohort study
Authors: Lyratzopoulos Georgios , McElduff Patrick , Heller Richard F , Hanily Margaret , Lewis Philip S
Published: April 2005

Background

In the UK, obesity is associated with a clear socioeconomic gradient, with individuals of lower socioeconomic status being more likely to be obese. Several previous studies, using individual measures of soecioeconomic status, have shown a more rapid increase in Body Mass Index (BMI) over time among adults of lower socioeconomic status. We conducted a study to further examine whether ecologically defined deprivation status influences within-individual BMI change during middle life, as the answer to this question can help determine optimal preventive strategies both for obesity per se, and its' associated socioeconomic disparities.

Methods

Anonymised records of participants to the Stockport population-based cardiovascular disease risk factor screening programme were analysed. Individuals aged 35–55 who had a first screening episode between 1989 and 1993, and a subsequent screening episode were included in the study. Deprivation status was defined using quintiles of the Townsend score. Mean annual BMI change by deprivation group was calculated using linear regression. Subsequently, deprivation group was included in the model as an ordinal variable, to test for trend. The modelling was repeated separately for individuals who were obese (BMI < 30) and non-obese at the time of first screening. In supplementary analysis, regression models were also adjusted for baseline BMI.

Results

Of 21,976 women and 19,158 men initially screened, final analysis included just over half of all individuals [11,158 (50.8%) women and 9,831 (51.3%) men], due to the combined effect of loss to follow-up and incomplete BMI ascertainment. In both sexes BMI increased by 0.19 kg/m2 annually (95% Confidence Intervals 0.15–0.24 for women and 0.16–0.23 for men). All deprivation groups had similar mean annual change, and there was no evidence of a significant deprivation trend (p = 0.801, women and 0.892, men). Restricting the analysis to individuals who were non-obese at baseline did not alter the results in relation to the lack of a deprivation effect. When restricting the analysis to individuals who were obese at baseline however, the findings were suggestive of an association of BMI increase with higher deprivation group, which was further supported by a significant association when adjusting for baseline BMI.

Conclusion

In the study setting, the BMI of non-obese individuals aged 35–55 was increasing over time independently of deprivation status; among obese individuals a positive association with higher deprivation was found. The findings support that socioeconomic differences in mean BMI and obesity status are principally attained prior to 35 years of age. Efforts to tackle inequalities in mean BMI and obesity status should principally concentrate in earlier life periods, although there may still be scope for focusing inequality reduction efforts on obese individuals even in middle life.
Attitudes to and management of fertility among primary health care physicians in Turkey: An epidemiological study
Authors: Hassa Hikmet , Ayranci Unal , Unluoglu Ilhami , Metintas Selma , Unsal Alaeddin
Published: April 2005

Background

The subject of infertility has taken its place in the health sector at the top level. Since primary health care services are insufficient, most people, especially women, keep on suffering from it all over the world, namely in underdeveloped or developing countries.

The aim of this study was to determine primary care physicians' opinions about the approach to infertility cases and their place within primary health care services (PHCSs).

Methods

The study was conducted between October 2003 and April 2004. The study group comprised 748 physicians working in PHCSs. They were asked to fill in a questionnaire with questions pertaining to infertility support, laboratory and treatment algorithms, as well as the demographic characteristics. The data was evaluated using the chi square test, percentage rates and a logistic regression model.

Results

The multivariate analyses showed that having a previous interest in infertility and having worked for a postgraduate period of between 5–9 years and ≥10 years were the variables that most positively influenced them in their approach to cases of infertility (p < 0.05, each one).

Just 28.7% of the physicians indicated that they believed cases of infertility could be evaluated at the primary care level. The most frequently proposed reason for indicating 'difficulty in practice' (n = 533) was inadequate provision of equipment in PHCSs (55.7%). The physicians reported that they were able to perform most of the supportive treatments and proposals (between 64.6%–87.7%). The most requested laboratory investigations were the instruction of patients in taking basal body temperatures and semen analysis (89.7% and 88.7%, respectively). The most preferential course of treatment was that of sexually transmitted diseases (95.5%).

Conclusion

It is clear that not enough importance is attached to the provision of care to infertile couples within PHCSs. This leads us to conclude that an integration of infertility services in primary care would be appropriate after strengthening the PHCSs.
Effect of a chemical manufacturing plant on community cancer rates
Authors: Mannes Trish , Emmett Katy , Willmore Alan , Churches Tim , Sheppeard Vicky , Kaldor Jill
Published: April 2005

Background

We conducted a retrospective study to determine if potential past exposure to dioxin had resulted in increased incidence of cancer in people living near a former manufacturing plant in New South Wales, Australia. During operation, from 1928 to 1970, by-products of the manufacturing process, including dioxin and other chemical waste, were dumped into wetlands and mangroves, discharged into a nearby bay and used to reclaim land along the foreshore, leaving a legacy of significant dioxin contamination.

Methods

We selected 20 Census Collector Districts within 1.5 kilometres of the former manufacturing plant as the study area. We obtained data on all cases of cancer and deaths from cancer in New South Wales from 1972 to 2001. We also compared rates for some cancer types that have been associated with dioxin exposure. Based on a person's residential address at time of cancer diagnosis, or at time of death due to cancer, various geo-coding software and processes were used to determine which collector district the case or death should be attributed to. Age and sex specific population data were used to calculate standardised incidence ratios and standardised mortality ratios, to compare the study area to two comparison areas, using indirect standardisation.

Results

During the 30-year study period 1,106 cases of cancer and 524 deaths due to cancer were identified in the study area. This corresponds to an age-sex standardised rate of 3.2 cases per 1,000 person-years exposed and 1.6 deaths per 1,000 person-years exposed. The study area had a lower rate of cancer and deaths from cancer than the comparison areas. The case incidence and mortality due to lung and bronchus carcinomas and haematopoietic cancers did not differ significantly from the comparison areas for the study period. There was no obvious geographical trend in ratios when comparing individual collector districts to New South Wales according to distance from the potential source of dioxin exposure.

Conclusion

This investigation found no evidence that dioxin contamination from this site resulted in increased cancer rates in the potentially exposed population living around the former manufacturing plant.
Assessing sensitivity to change: choosing the appropriate change coefficient
Authors: Stratford Paul W , Riddle Daniel L
Published: April 2005

The past 20-years have seen the development and evaluation of many health status measures. Unlike the high standards demanded of those who conduct and report clinical intervention trials, the methodological rigor for studies examining the sensitivity to change of health status measures are less demanding. It is likely that the absence of a criterion standard for change in health status contributes to this shortcoming. To increase confidence in the results of these types of studies investigators have often calculated multiple change coefficients for the same patient sample.

The purpose of this report is to identify the conflict that arises when multiple change coefficients are applied to the same patient sample.

Three families of change coefficients based on different assumptions concerning the sample composition are identified: (1) the sample is homogeneous with respect to change; (2) subgroups of patients who truly change by different amounts exist; (3) individual patients, many of whom truly change by different amounts exist. We present several analyses which illustrate a major conceptual conflict: the signal (a measure's true ability to detect change) for some of these coefficients appears in the noise term (measurement error) of the others.

We speculate that this dilemma occurs as a result of insufficient preparatory work such as pilot studies to establish the likely change characteristic of the patient population of interest. Uncertainty in the choice of change coefficient could be overcome by conducting pilot studies to ascertain the likely change characteristic of the population of interest. Once the population's change characteristic is identified, the choice of change coefficient should be clear.
Parental exercise is associated with Australian children's extracurricular sports participation and cardiorespiratory fitness: A cross-sectional study
Authors: Cleland Verity , Venn Alison , Fryer Jayne , Dwyer Terence , Blizzard Leigh
Published: April 2005

Background

The relationship between parental physical activity and children's physical activity and cardiorespiratory fitness has not been well studied in the Australian context. Given the increasing focus on physical activity and childhood obesity, it is important to understand correlates of children's physical activity. This study aimed to investigate whether parental exercise was associated with children's extracurricular sports participation and cardiorespiratory fitness.

Methods

The data were drawn from a nationally representative sample (n = 8,484) of 7–15 year old Australian schoolchildren, surveyed as part of the Australian Schools Health and Fitness Survey in 1985. A subset of 5,929 children aged 9–15 years reported their participation in extracurricular sports and their parents' exercise. Cardiorespiratory fitness was measured using the 1.6 km (1-mile) run/walk and in addition for children aged 9, 12 or 15 years, using a physical work capacity test (PWC170).

Results

While the magnitude of the differences were small, parental exercise was positively associated with children's extracurricular sports participation (p < 0.001), 1.6 km run/walk time (p < 0.001) and, in girls only, PWC170 (p = 0.013). In most instances, when only one parent was active, the sex of that parent was not an independent predictor of the child's extracurricular sports participation and cardiorespiratory fitness.

Conclusion

Parental exercise may influence their children's participation in extracurricular sports and their cardiorespiratory fitness levels. Understanding the correlates of children's extracurricular sport participation is important for the targeting of health promotion and public health interventions, and may influence children's future health status.
The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration
Authors: Le Maitre Christine Lyn , Freemont Anthony J , Hoyland Judith Alison
Published: April 2005

In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1β-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family.

This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1β-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6).

In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration.
Mutations in Human Urate Transporter 1 Gene in Presecretory Reabsorption Defect Type of Familial Renal Hypouricemia
Authors: Wakida Naoki , Tuyen Do Gia , Adachi Masataka , Miyoshi Taku , Nonoguchi Hiroshi , Oka Toshiaki , Ueda Osamu , Tazawa Masahiro , Kurihara Satoshi , Yoneta Yoshitaka , Shimada Hajime , Oda Takashi , Kikuchi Yuichi , Matsuo Hirotaka , Hosoyamada Makoto , Endou Hitoshi , Otagiri Masaki , Tomita Kimio , Kitamura Kenichiro
Published: April 2005

To date, 11 loss of function mutations in the human urate transporter 1 (hURAT1) gene have been identified in subjects with idiopathic renal hypouricemia. In the present studies we investigated the clinical features and the mutations in the hURAT1 gene in seven families with presecretory reabsorption defect-type renal hypouricemia and in one family with the postsecretory reabsorption defect type. Twelve affected subjects and 26 family members were investigated. Mutations were analyzed by PCR and the direct sequencing method. Urate-transporting activities of wild-type and mutant hURAT1 were determined by [14C]urate uptake in Xenopus oocytes. Mutational analysis revealed three previously reported mutations (G774A, A1145T, and 1639–1643 del-GTCCT) and a novel mutation (T1253G) in families with the presecretory reabsorption defect type. Neither mutations in the coding region of hURAT1 gene nor significant segregation patterns of the hURAT1 locus were detected in the postsecretory reabsorption defect type. All hURAT1 mutants had significantly reduced urate-transporting activities compared with wild type (P < 0.05; n = 12), suggesting that T1253G is a loss of function mutation, and hURAT1 is responsible for the presecretory reabsorption defect-type familial renal hypouricemia. Future studies are needed to identify a responsible gene for the postsecretory reabsorption defect-type familial renal hypouricemia.
Small, Dense Lipoprotein Particles and Reduced Paraoxonase-1 in Patients with the Metabolic Syndrome
Authors: Garin Marie-Claude Blatter , Kalix Barbara , Morabia Alfredo , James Richard W.
Published: April 2005

The presence of the metabolic syndrome (World Health Organization definition) and its association with lipoprotein abnormalities suggestive of greater susceptibility to oxidative stress have been analyzed in patients with angiographically defined coronary artery disease. The odds ratio for the presence of the metabolic syndrome was significantly higher in coronary artery disease-positive patients (P < 0.001). The metabolic syndrome was also associated with more severe coronary disease (P < 0.01). Patients with the metabolic syndrome had significantly decreased low-density lipoprotein-cholesterol/apolipoprotein B and high-density lipoprotein-cholesterol/apolipoprotein AI ratios, indicative of the presence of small, dense lipoprotein particles. The syndrome was also associated with reduced concentrations and activities of the antioxidant enzyme, paraoxonase-1. The metabolic syndrome is characterized by smaller, denser lipoprotein particles that increase their susceptibility to oxidative modifications and diminished serum paraoxonase-1, which is a major determinant of the antioxidant capacity of high-density lipoproteins. These may be contributory factors to the increased presence and severity of coronary disease in such patients.