bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Fluorescent Polymerase Chain Reaction versus Cytogenetics: Risk-Related Indication and Clinical Implication of Nondetected Chromosomal Disorders
Authors: Kozlowski P. , Grund I. , Hickmann G. , Stressig R. , Knippel A.J.
Published: February 2006

Background: The rapid detection of aneuploidies by quantitative fluorescent polymerase chain reaction (QF-PCR) allows reliable prenatal diagnosis of trisomies 21, 18, and 13. Discussion has been raised as to whether single QF-PCR could be an alternative to traditional cytogenetic karyotyping for certain referral categories. Objective: To evaluate an indication-based classification of cases at risk of missing clinically relevant chromosomal disorders by QF-PCR. Methods: From October 1999 to November 2003, 4,682 of 14,123 patients referred for amniocentesis decided to have QF-PCR as a rapid adjunct to conventional cytogenetic evaluation. Patients were classified according to the risk of missing chromosomal abnormalities by QF-PCR based on anamnestic risk and ultrasound prior to amniocentesis. The results in these two defined categories were compared in relation to the clinical significance of cytogenetic results. Results: QF-PCR and conventional cytogenetic analysis had concordant results in 4,617 of 4,682 (98.6%) cases. Thirty-six of 110 (32.2%) clinically significant chromosomal abnormalities were missed by QF-PCR. Patients classified not to be at risk of missing chromosomal abnormalities using QF-PCR had a residual risk of 1/166 (0.6%) for chromosomal distortions of clinical significance. Conclusion: Classification by anamnestic and sonographic data does not specifically identify patients at risk of structural abnormalities. Clinical relevance of the nondetected anomalies essentially justifies traditional karyotyping regardless of risk classification.
Cystic Colon Duplication as Differential Diagnosis to Ovarian Cyst
Authors: Meyberg-Solomayer G.C. , Buchenau W. , Solomayer E.-F. , Fehm T. , Hacker H.W. , Wallwiener D. , Poets C.
Published: February 2006

Objective: We report the case of a female fetus with a single spherical anechoic cyst on the right side of the lower abdomen first diagnosed at 22 weeks of pregnancy. Methods: Serial ultrasound monitoring and needle aspiration of the cyst were performed. Results: The cyst grew during pregnancy up to 8 cm diameter. Needle aspiration was performed at 33 and 36 weeks. At 38 weeks labor was induced and a girl was delivered spontaneously. Postnatally the child showed abdominal distention, vomiting, and an obstruction of venous return of the right leg. To improve venous circulation, another needle aspiration of the cyst was performed. Laparoscopy revealed cystic colon duplication. Conclusions: Prenatal differentiation of a single round anechoic cyst in the pelvis of a female fetus can be difficult. As a rare abnormality cystic colon duplication has to be considered.
Insight into Biofilm-Associated Microbial Life
Authors: Bhinu V.S.
Published: February 2006

Microbes cohabit our planet and are engaged in a struggle for survival though on a microscopic scale. This endeavor allows them to develop and devise means for survival and proliferation. One such strategy is the formation of biofilms leading to establishment of a protected community. Such multi-communities may consist of harmful and pathogenic microbes, and they may cause economic problems and threats to human health. Biofilms are formed when microorganisms are typically attached to support surfaces. Biofilm-associated cells are sessile and differentiated from their suspended counterparts by generation of an extracellular polymeric substance matrix, reduced growth rates, and the up- and downregulation of specific genes. Biofilm formation is a complex process regulated by diverse characteristics of the growth medium, substratum, and cell surface. Development of strategies to control or prevent biofilms requires a thorough understanding of the biofilm development process. Biofilm research has witnessed exponential growth, and exciting findings have been reported. This has led us to visualize some previously unthought-of and fascinating events. This article aims to provide an overview of biofilm research and associated challenges.
CadC-Mediated Activation of the cadBA Promoter in Escherichia coli
Authors: Küper Christoph , Jung Kirsten
Published: February 2006

The transcriptional activator CadC in Escherichia coli, a member of the ToxR-like proteins, activates transcription of the cadBA operon encoding the lysine decarboxylase CadA and the lysine-cadaverine antiporter CadB. cadBA is induced under conditions of acidic external pH and exogenous lysine; anoxic conditions raise the expression level up to 10 times. To characterize the binding mechanism of CadC, procedures for the purification of this membrane-integrated protein and its reconstitution into proteoliposomes were established. The binding sites of CadC upstream of the cadBA promoter region were determined by in vitro DNaseI protection analysis. Two regions were protected during DNaseI digestion, one from –144 to –112 bp, designated Cad1, and another one from –89 to –59 bp, designated Cad2. Binding of purified CadC to Cad1 and Cad2 was further characterized by DNA-binding assays, indicating that CadC was able to bind to both DNA fragments. Genetic analysis with promoter-lacZ fusions confirmed that both sites, Cad1 and Cad2, are essential for activation of cadBA transcription. Moreover, these experiments revealed that binding of H-NS upstream of the CadC-binding sites is necessary for repression of cadBA expression at neutral pH and under aerobic conditions. Based on these results, a model for transcriptional regulation of the cadBA operon is proposed, according to which H-NS is involved in the formation of a repression complex under non-inducing conditions. This complex is dissolved by binding of CadC to Cad1 under inducing conditions. Upon binding of CadC to Cad2 cadBA expression is activated.
Regulation of pho Regulon Gene Expression by the Carbon Control Protein A, CcpA, in Bacillus subtilis
Authors: Choi Soo-Keun , Saier Jr. Milton H.
Published: February 2006

Bacterial regulons involved in carbon, nitrogen and phosphorus metabolism must interact for purposes of coordination, but the mechanisms involved are not understood. We here report that the carbon control pro-tein-A (CcpA) of Bacillus subtilis, primarily concerned with carbon metabolism, influences expression of various phosphorus (pho) regulon genes including the two alkaline phosphatase structural genes, phoA and phoB. The directions and magnitudes of the effects of glucose and the loss of CcpA on these two genes depend on growth conditions, but they always correlate inversely. Absolute expression levels of phoA and phoB depend on a rich nitrogen source, and gene activation by a fermentable substrate such as glucose depends on the presence of a respiratory substrate such as succinate. We show that these CcpA-dependent glucose effects can be explained by the effects of glucose and CcpA acting on the phoPR operon. Although a good CcpA-binding site (CRE) is found in the control region of the phoPR operon, direct regulation of phoPR gene expression by CcpA via this CRE could not account for the effects of glucose and CcpA on phoA and phoB gene expression. We conclude that CcpA exerts indirect control over the pho regulon by a mechanism that involves CcpA and PhoRP but does not involve the phoPR operon CRE.
Expression of Recombinant Streptolysin O and Specific Antibody Production
Authors: Kimoto Hisashi , Fujii Yutaka , Hirano Satoko , Yokota Yoshifumi , Taketo Akira
Published: February 2006

Streptolysin O (SLO), an oxygen-labile cytolysin, is the cholesterol-binding exotoxin of hemolytic streptococci. Besides microbiological and pathological interests, this cytolysin has been used as a tool for permeabilization of biomembranes. SLO serves as a diagnostic reagent for determination of anti-SLO antibody titer in streptococcal infection. Availability of highly purified SLO, however, has been limited by low yield in streptococcal culture and purification process. Present subcloning of mature-type full-length SLO gene into an expression vector having strictly controllable araBAD promoter enabled efficient production of the cytolysin. Further, anti-SLO antibody with high specificity was obtained by immunizing with purified SLO protein.
Cholesterol 25-Hydroxylase on Chromosome 10q Is a Susceptibility Gene for Sporadic Alzheimer’s Disease
Authors: Papassotiropoulos Andreas , Lambert Jean-Charles , Wavrant-De Vrièze Fabienne , Wollmer M. Axel , von der Kammer Heinz , Streffer Johannes R. , Maddalena Alessia , Huynh Kim-Dung , Wolleb Sibylle , Lütjohann Dieter , Schneider Brigitte , Thal Dietmar R. , Grimaldi Luigi M.E. , Tsolaki Magdalini , Kapaki Elisabeth , Ravid Rivka , Konietzko Uwe , Hegi Thomas , Pasch Thomas , Jung Hans , Braak Heiko , Amouyel Philippe , Rogaev Evgeny I. , Hardy John , Hock Christoph , Nitsch Roger M.
Published: February 2006

Alzheimer’s disease (AD) is the most common cause of dementia. It is characterized by β-amyloid (Aβ) plaques, neurofibrillary tangles and the degeneration of specifically vulnerable brain neurons. We observed high expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that has been previously linked to sporadic AD. Sequencing of the 5′ region of CH25H revealed three common haplotypes, CH25Hχ2, CH25Hχ3 and CH25Hχ4; CSF levels of the cholesterol precursor lathosterol were higher in carriers of the CH25Hχ4 haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five independent populations, a common variation in the vicinity of CH25H was significantly associated with the risk for sporadic AD (p = 0.006). Quantitative neuropathology of brains from elderly non-demented subjects showed brain Aβ deposits in carriers of CH25Hχ4 and CH25Hχ3 haplotypes, whereas no Aβ deposits were present in CH25Hχ2 carriers. Together, these results are compatible with a role of CH25Hχ4 as a putative susceptibility factor for sporadic AD; they may explain part of the linkage of chromosome 10 markers with sporadic AD, and they suggest the possibility that CH25H polymorphisms are associated with different rates of brain Aβ deposition.
Increased Cerebrospinal Fluid Aβ38/Aβ42 Ratio in Alzheimer Disease
Authors: Mehta Pankaj D. , Pirttila Tuula
Published: February 2006

We quantitated amyloid β peptide (Aβ) 38, Aβ40 and Aβ42 levels in matched CSF and plasma from Alzheimer disease (AD) patients and controls. CSF Aβ38 and Aβ40 levels were similar in AD patients and in controls; however, they were higher in controls with APOE υ4 allele than those without. CSF Aβ42 levels were lower in AD patients than in controls. The CSF Aβ38/42 ratio was higher in AD patients than controls, consistent with the previously reported higher Aβ40/42 ratio. Aβ38, Aβ40 and Aβ42 levels in plasma were similar in AD patients and in controls and showed no relationship to levels in CSF. Our findings suggest that the increased CSF Aβ38/42 ratio found in AD patients is derived entirely from reduction of CSF Aβ42 levels.
Aβ Immunotherapy: Lessons Learned for Potential Treatment of Alzheimer’s Disease
Authors: Schenk Dale B. , Seubert Peter , Grundman Michael , Black Ron
Published: February 2006

Amyloid-β (Aβ) immunotherapy for treatment of Alzheimer’s disease (AD) was first described in 1999 and has been very informative regarding the role of Aβin AD. Through the efforts of many laboratories we now know that it is possible to reduce amyloid burden and many related AD pathologies in numerous animal models of the disease. Furthermore, initial clinical testing with AN1792, composed of Aβ1–42 and an adjuvant, has yielded very important insights into both the clinical potential of the approach and the impact of Aβpeptide on the disease. A brief review of our current understanding of Aβimmunotherapy is described. These findings have led to newer alternative Aβimmunotherapy approaches that include both active and passive approaches that are currently in clinical testing in both the USA and Europe.
Awareness about Glaucoma and Related Eye Health Attitudes in Switzerland: A Survey of the General Public
Authors: Mansouri Kaweh , Orgül Selim , Meier-Gibbons Frances , Mermoud André
Published: February 2006

Objective: To assess the level of awareness about glaucoma and its consequences and to evaluate associated eye health attitudes in a randomly selected general urban and rural population in Switzerland. Methods: A cluster random sample of the Swiss population was interviewed. Five-hundred and two telephone interviews with subjects who were representative of the 35- to 70-year-old population of the German- and French-speaking parts of Switzerland were conducted. Data were collected about their gender, age, educational status and professional situation. Study Type: Cross-sectional survey. Results: In total, 76% (n = 383) of respondents did not have any (or any correct) association with the term ‘glaucoma’. Only 24.7% (n = 123) of the interviewees could describe glaucoma as an eye condition. Awareness of glaucoma was independent of age, gender, educational status, and household income. Associated therapeutic measures were surgery (75%) and medical treatment (57%). Seventy-one percent of all respondents wear eyeglasses, 74% of all females and 67% of males. Conclusion: Awareness and knowledge about glaucoma are relatively low in the average Swiss population across all segments of society. The lack of awareness on this insidious disease has important implications for the uptake of ophthalmic care and may result in avoidable blindness. These data also show that the ophthalmologist is considered by the majority of people to be the primary contact for eye health-related information and sight corrections.
Hypothermia Protects Cultured Human Retinal Pigment Epithelial Cells against Trypan Blue Toxicity
Authors: Kunikata Hiroshi , Tomita Hiroshi , Murata Hiromi , Sagara Yoshiko , Sato Hajime , Wada Yuko , Fuse Nobuo , Nakagawa Yoichi , Abe Toshiaki , Tamai Makoto
Published: February 2006

Purpose: To determine whether trypan blue (TB) is toxic to cultured human retinal pigment epithelial (ARPE-19) cells, and whether hypothermia can protect ARPE-19 cells against TB toxicity. Methods: ARPE-19 cells were cultured and exposed to balanced salt solution as a control, while other cells were exposed to 0.05, 0.2, and 0.5% TB dye at 37 and 4°C for 5 and 30 min. The percentage of ARPE-19 cells that survived was determined by resazurin 1 day after the exposure. Results: A statistically significant decrease in the percentage of ARPE-19 cells surviving was found after exposure to 0.2 and 0.5% TB at any temperature or for any exposure duration (p < 0.01). The percentage of RPE cells surviving at 0.05% was not significantly different from that of controls except for a 30-min exposure at 37°C. The percentage of cells surviving at 4°C for a 5-min exposure to 0.5% TB and a 30-min exposure to 0.2 and 0.5% was significantly higher than that at 37°C under each condition (p < 0.01 for all). Conclusions: These results indicate that TB is toxic to human RPE cells, and the toxicity is dose- and exposure duration-dependent. Exposing the cells at 4°C had a protective effect against higher concentrations or longer exposure durations of TB compared to exposure at 37°C.
Endophthalmitis with Retinal Necrosis following Intravitreal Triamcinolone Acetonide Injection
Authors: Aggermann Tina , Stolba Ulrike , Brunner Simon , Binder Susanne
Published: February 2006

A 69-year-old man with heterozygote factor V Leiden mutation and a history of central retinal vein occlusion in his left eye complained of decreased visual acuity in his right eye. Macular edema and ischemic CRVO were diagnosed. Following an intravitreal injection of 4 mg triamcinolone acetonide, endophthalmitis and necrotizing retinopathy developed, clinically resembling necrotizing herpetic retinopathies as have been described in immuno-compromised patients. An endogenous viral infection due to a steroid-induced immune suppression may be another complication of intravitreal injections of corticosteroids.
Diagnosis and Treatment of Endogenous Fungal Endophthalmitis
Authors: Williams Michael A. , McMullan Ronan , Hedderwick Sara , Mulholland David A. , Best Richard M.
Published: February 2006

Endogenous infectious endophthalmitis is rare, and a primary source is usually identified. A case of primary fungal endophthalmitis successfully treated with vitrectomy and systemic antifungal therapy is presented. The aetiology and treatment of the condition are discussed.
Does Inflammatory Linear Verrucous Epidermal Nevus Represent a Segmental Type 1/Type 2 Mosaic of Psoriasis?
Authors: Hofer Thomas
Published: February 2006

Background: A 6-year-old girl with a symmetric linear eruption on both of her legs, clinically and histologically resembling inflammatory linear verrucous epidermal nevus (ILVEN) or linear psoriasis (LP), with concomitant psoriasis of the guttata type and a positive family history of psoriasis is presented. The questions as to whether LP actually exists and ILVEN represents a distinct entity are still under debate. Objective and Methods: The recent literature concerning case reports of ILVEN and LP is reviewed. Results: Case reports of ILVEN and LP can be subdivided into four different groups: (1) ILVEN with or without concomitant psoriasis, only in part reacting to antipsoriatic treatment, (2) ILVEN without concomitant psoriasis, (3) LP with concomitant psoriasis vulgaris, with both groups 2 and 3 reacting successfully to antipsoriatic treatment, and (4) LP without concomitant psoriasis vulgaris and with no family history of psoriasis (very rarely reported). Conclusion: It is hypothesized that inflammatory linear verrucous eruption besides nevoid psoriasis/LP represents a further segmental type 1/type 2 mosaic of psoriasis which, if a (verrucous) epidermal nevus exists, shows a high affinity of occurrence in close context to such a nevus. Heritability is thought to be possible.
Risk Factors for Erysipelas of the Leg in Tunisia: A Multicenter Case-Control Study
Authors: Mokni Mourad , Dupuy Alain , Denguezli Mohamed , Dhaoui Raouf , Bouassida Samir , Amri Montacer , Fenniche Sami , Zeglaoui Faten , Doss Nejib , Nouira Rafiaa , Osman-Dhahri Amel Ben , Zili Jamel , Mokhtar Insaf , Kamoun Mohamed Ridha , Zahaf Abdelmajid , Chosidow Olivier
Published: February 2006

Background: Risk factors for erysipelas (cellulitis) were rarely evaluated in controlled studies. Regional variations of these risk factors have never be assessed. Objective: To assess risk factors for erysipelas of the leg in Tunisia. Subjects and Methods: Case-control study in seven hospital centers in Tunisia. Cases were 114 consecutive patients with erysipelas of the leg [sudden onset (<24 h) of a well-demarcated dermo-hypodermatitis with fever or chills]. Two controls were matched to each case for age, sex, and hospital (n = 208). Main outcome measures are local and general suspected risk factors for erysipelas of the leg. Results: In multivariate analysis, disruption of the cutaneous barrier (i.e. traumatic wound, toe-web intertrigo, excoriated leg dermatosis or plantar squamous lesions) and leg edema were independently associated with erysipelas of the leg, with respective odds ratios of 13.6 (95% confidence interval: 6.0–31) and 7.0 (1.3–38). No association was observed with diabetes, alcoholism, or smoking. Conclusions: We confirmed the major role of local risk factors and the minor role of general risk factors for erysipelas of the leg, in a setting different than the one previously studied. Detecting and treating toe-web intertrigo and traumatic wounds should be considered in the prevention of erysipelas of the leg.
Heredity: A Prognostic Factor for Acne
Authors: Ballanger F. , Baudry P. , N’Guyen J.M. , Khammari A. , Dréno B.
Published: February 2006

Background: The role of heredity in acne severity and therapeutic response remains unclear. Objective: A prospective epidemiologic study was performed to compare clinical and evolutive features of acne and response to treatment in 151 patients with acne with (A+) or without (A–) family history of acne. Methods: A+ and A– patients were compared on clinical and therapeutic criteria. A+ patients were then distributed into subgroups (M+, F+, M+F+) following the origin of family history (father: F, mother: M). Results: The clinical profile was similar in the A+ and A– populations. Acne occurred earlier and more often before puberty in the A+ population, in which oral treatments and relapse after isotretinoin were more frequent. Retentional lesions (number and extent) were more important in the M+ and M+F+ populations. Conclusion: This study confirms the importance of heredity as a prognostic factor for acne. Family history of acne is associated with earlier occurrence of acne, increased number of retentional lesions and therapeutic difficulties.
Comparison of a Two- or Three-Week Regimen and a Review of Treatment of Erythema Migrans with Phenoxymethylpenicillin
Authors: Aberer E. , Kahofer P. , Binder B. , Kinaciyan T. , Schauperl H. , Berghold A.
Published: February 2006

Background: A longer duration treatment is preferred in erythema migrans (EM) to prevent late complaints. Objectives: To determine whether 20 (20d-pt) or 14 days (14d-pt) of phenoxymethylpenicillin (PenV) have similar efficacy in treating EM and preventing further sequelae. Patients and Methods: In a prospective double-centre study, 102 patients with EM were treated with PenV 1.5 million IU thrice daily for either 20 or 14 days and followed up for 12 months. Results: The primary cure rate after treatment with PenV was 91.5% (79.6–97.6) for 20d-pt vs. 91.7% (77.5–98.2) for 14d-pt; p > 0.99). In 7 patients (4/20d-pt and 3/14d-pt), persistent or newly arising symptoms required retreatment. After 1 year, all patients were cured. The immune response showed no statistical difference between the treatment groups in the follow-up period. Conclusion: A 2-week treatment regimen of PenV seems to be as effective as a 3-week course with no statistical differences for clinical and serological findings after treatment.
Prospective Study of Risk Factors of Relapse after Treatment of Acne with Oral Isotretinoin
Authors: Quéreux G. , Volteau C. , N’Guyen J.M. , Dréno B.
Published: February 2006

Background: The effectiveness of oral isotretinoin against acne is undeniable. However, few data on the maintenance of effect after treatment termination have been published. Objective: The purpose of the study was to identify the risk factors of relapse after stopping isotretinoin. Method: This prospective open study examined 52 patients with moderate to severe acne at the Dermatological Clinic of the Nantes University Hospital (France). Variables likely to influence relapse were studied using the Cox model. Results: 27 patients (52%) relapsed after stopping treatment. In multivariate analysis, severe seborrhoea and a high score of inflammatory lesions at the end of the treatment, an early age, a family history of acne, prepubertal acne and acne extended to the trunk were the factors increasing significantly the risk of relapse. Conclusion: Our data allow to define more precisely the profile of acne patients for whom the risk of relapse is highest and who should therefore be followed up quite regularly after treatment termination.
Granulomatous Dermatitis with Enlarged Histiocytes: A Characteristic Pattern of Granulocyte Colony-Stimulating Factor
Authors: Ferran Marta , Gallardo Fernando , Salar Antonio , Iglesias Mar , Barranco Carlos , Pujol Ramon M.
Published: February 2006

Two patients developed a pruritic maculopapular rash following treatment with granulocyte colony-stimulating factor (G-CSF). Histopathological examination disclosed a superficial dermal inflammatory infiltrate composed of interstitially arranged large histiocytic CD68+ cells and perivascularly disposed lymphocytes. Large histiocytes were interspersed among the collagen bundles with associated slight deposits of mucin. Elastophagocytosis was occasionally observed, and a slight reduction of dermal elastic fibers was also noted. There was no evidence of frank granuloma formation, fibrosis or significant changes of collagen bundles. This histopathological variant of granulomatous dermatitis with ‘enlarged histiocytes’ seems to be characteristic of an unusual cutaneous reaction secondary to CSF treatment.
What Role for Public Health in Genetics and Vice Versa?
Authors: Holtzman Neil A.
Published: February 2006

Some epidemiologists and geneticists claim that integrating genetics into public health policies and programs is necessary and unavoidable. Objective: To examine the extent to which further integration of public health and genetics is warranted. Methods: Synthesis of the literature in four areas: research, genetic services, regulation, and education. The analysis is limited to human genetics. Results: Public support for basic genetic research has and will continue to lead to new applications and to further understanding of human origins and dispersions. Some applied research, particularly for genetic risk factors for common complex diseases, has low yield and is better supported by private funds. The only genetic service for which a public health role is paramount is newborn screening. With the patenting of genes, and the proliferation of commercial interests in genetic tests and directly advertising them to the public, regulation by public health agencies is increasingly important. As most genetic testing and other services will be provided in the personal health care system, education about genetics is best left to the educational and medical systems. Public health practitioners should be aware of the limitations of genetic tests. Conclusions: There is little need for further integration of genetic services and education into public health especially in countries in which public and private health services are dichotomized. Newborn screening and follow-up, however, are most safely and effectively provided under public health auspices. The most important area for strengthening the public health role is in the regulation of genetic tests and other genetic services provided primarily by the private sector. Continued support for basic genetic research is needed.
Managing Partnerships and Impact on Decision-Making: The Example of Health Technology Assessment in Genetics
Authors: Blancquaert Ingeborg
Published: February 2006

For an emerging field such as Public Health Genetics, the partnerships that will be developed with stakeholders are of strategic importance, since they may affect long-term impact on policy-making. A concrete example in the field of health technology assessment in genetics was chosen to illustrate how the context in which scientific advisory bodies operate and the nature of partnerships developed over time influence the impact on decision-making at different levels, from the micro (professional) level through the meso (institutional) level to the macro (policy) level. As pointed out in the knowledge transfer literature, impact is not only reflected by instrumental use of knowledge, but also by problem-framing and strategic use of knowledge. Solid partnerships at the micro level, with researchers and health care professionals, are essential to build credibility and trust, and they lay the groundwork for contextualized and relevant advice and potential impact at the policy level. Even though maintaining the necessary critical distance with respect to all stakeholders is easier for institutions that are at arm’s length from government, achieving the right balance between an institution’s independence and service relationship is a real challenge.
The Spectre of Coercion: Is Public Health Genetics the Route to Policies of Enforced Disease Prevention?
Authors: van den Daele Wolfgang
Published: February 2006

The paper discusses options for disease prevention in Public Health Genetics and attempts to assess the probability that coercive strategies might be chosen in public health policies that impose duties to undergo genetic testing. Given the social values, legal and political cultures and professional orientations in Western Europe and the United States, which provide the terms of reference for this assessment, it is unlikely that the preventive options which might emerge from human genetics in the future will trigger policies that force preventive behavior upon people, except in the cases where such enforcement is designed to protect third parties.
Pharmacogenetics, Adverse Drug Reactions and Public Health
Authors: Kollek Regine , van Aken Jan , Feuerstein Günter , Schmedders Mechtild
Published: February 2006

Adverse drug reactions (ADRs) are a major public health problem. Pharmacogenetic testing prior to drug treatment is supposed to considerably alleviate this problem. The state of pharmacogenetic development was assessed by a systematic literature review, supplemented by expert interviews. Analysis of three case examples revealed that – with the exception of thiopurine methyltransferase (TPMT) – studies are lacking which unambiguously prove the clinical value of pharmacogenetic testing. Testing can prevent some, but by far not all ADRs. Since it does not compensate for clinical monitoring, pharmacogenetics can be regarded as add-on technology, applied in addition to established methods. A non-representative, explorative survey conducted amongst members of the German Society of Laboratory Medicine revealed that the demand for testing is limited and has not increased much, although a certain increase is expected in the future.
Genetic Counseling for the Public?
Authors: Kunstmann Erdmute , Epplen Jörg T.
Published: February 2006

The widespread availability of diagnostic tools for numerous inherited diseases requires diligent decision-making regarding the risks and benefits, not only for the individual but also at the population level. Should therefore genetic counseling be offered to the entire population at risk for genetic diseases? In our opinion, the goals of public health may only be reached by serving primarily the individual at risk and his/her family. Efforts in public health genetics should be focused on appropriate genetic counseling, especially regarding common diseases with complex genetic components in the near future.
Sequence Variability of Human Cytomegalovirus UL146 and UL147 Genes in Low-Passage Clinical Isolates
Authors: He Rong , Ruan Qiang , Qi Ying , Ma Yan-Ping , Huang Yu-Jing , Sun Zheng-Rong , Ji Yao-Hua
Published: February 2006

Objectives: Human cytomegalovirus (HCMV) infects a number of organs and cell types in vivo. The different symptoms and tissue tropisms of HCMV infection perhaps result from the genetic polymorphism. A new region of DNA containing at least 19 open reading frames (ORFs – denoted UL133–151) was found in the low-passage HCMV clinical strain Toledo and several other low-passage clinical isolates, but not present in the HCMV laboratory strain AD169. Two of these genes, UL146 and UL147, encode proteins with sequence characteristics of CXC (α) chemokines, suggesting that they might influence the behavior of neutrophils during infection. This research was to study the sequence variability of UL146 and UL147 ORFs in HCMV clinical isolates and examine the possible associations between gene variability and the outcome of HCMV infection. Methods: UL146 and UL147 genes from strains obtained from suspected congenitally HCMV-infected infants were PCR amplified and sequenced. Results: High variability was found in UL146 and UL147 gene among HCMV clinical strains. However, the α chemokine motif in UL146 and UL147 genes was conserved in almost all sequences. According to the phylogenetic analysis, all sequences of UL146 in clinical isolates could be divided into three groups. All strains from congenital megacolon infants existed in G2A only, and all from asymptomatic infants existed in G2B peculiarly. Conclusions: Sequence variability among HCMV clinical strains may affect the ability of UL146 and UL147 to attract human neutrophils and influence viral dissemination. No obvious linkage was observed between UL146 polymorphisms and outcome of suspected congenital HCMV infection.
222 Base Pairs in NS5B Region and the Determination of Hepatitis C Virus Genotype 6
Authors: Chinchai Teeraporn , Noppornpanth Suwanna , Bedi Kavita , Theamboonlers Apiradee , Poovorawan Yong
Published: February 2006

Objective: The present study was performed to genotype hepatitis C virus (HCV) by direct sequencing of a 222-bp nucleotide in the NS5B region and comparing the results with those of direct sequencing in the core region. We investigated a new region for HCV genotyping which gave the best performance to discriminate HCV genotype 6a, the unique genotype found in Southeast Asia. Methods: Plasma samples taken from 57 HCV-infected blood donors were used in this study. RT-PCR products were amplified using primers located in the NS5B region. The 222-bp PCR products were purified and sequenced. The genotype of HCV isolates were obtained by phylogenetic analysis and compared with HCV reference strains stored in the GenBank database. The HCV sequences clustering in the same node were considered to be of the same genotype. Results: Thirty-one, 22 and 4 samples of HCV genotype 3a, 1a and 1b, respectively, were analyzed by this method. Upon comparison with genotyping in the core region, 86 and 14% of the samples yielded concordant and discordant genotype results, respectively. The majority of discordant results (63%; 5 of 8) was observed with HCV genotype 6a which yielded 6a upon core sequencing as opposed to 1a or 3a upon NS5B sequencing. Conclusion: HCV genotype 6a obtained by direct sequencing in the core region could not be unequivocally arrived at by sequencing 222 bp in the NS5B region. Hence, sequencing in the core region is preferable for genotyping our specimens, even though longer PCR products are required as this method enables discrimination between genotype 6a and the remaining genotypes.
Impact of Stroke Syndrome and Stroke Severity on the Process of Consent in the Third International Stroke Trial
Authors: Kane Ingrid , Lindley Richard , Lewis Steff , Sandercock Peter
Published: February 2006

Background: Obtaining informed consent for a patient’s participation in a randomized trial of treatment for use in a medical emergency may be achieved in a variety of ways. We sought to assess the process of consent and to evaluate the influence of the patient’s neurological deficit on the method used to obtain consent in the first 300 patients recruited into the Third International Stroke Trial (IST-3). Methods: IST-3 is the first large-scale randomized controlled trial of intravenous thrombolysis in acute ischaemic stroke. The clinician could use one of four procedures to recruit the patient: written consent, witnessed consent, assent, or a waiver of consent. The patient’s neurological deficits were recorded at baseline. We analysed the relationship between the neurological deficits at baseline and the consent procedure. Results: The method of consent used was written consent in 71 subjects (24%), witnessed verbal consent in 30 subjects (10%), assent by a relative in 197 subjects (66%), and waiver of consent in 2 subjects (1%). Patients with severe neurological deficits (as measured either by their stroke syndrome or their lower predicted probability of being alive and independent at 6 months) were more likely to be recruited by assent. Patients able to give written consent had less severe strokes. Conclusions: Patients with non-lacunar hemispheric stroke syndromes or with a more severe neurological deficit were less likely to give written consent. Excluding such patients from acute stroke treatment trials would eliminate many otherwise eligible subjects, who have a poor predicted outcome without treatment and yet might benefit from acute treatments such as thrombolysis. Flexible consent procedures developed for IST-3 have made it feasible to recruit the target population.
Adherence to Aspirin in Secondary Prevention of Ischemic Stroke
Authors: Lago Aida , Tembl Jose Ignacio , Pareja Ana , Ponz Alejandro , Ferrer Jose Manuel , Vallés Juana , Santos Maria Teresa
Published: February 2006

Objective: Compliance with antiplatelet therapy is essential for the efficiency of secondary prevention of ischemic stroke. The objective of this study was to evaluate adherence to aspirin treatment in patients with ischemic stroke. Patients and Methods: We studied outpatients of 5 neurological ambulatory centers in an urban city, Valencia, all with a history of ischemic stroke who had received aspirin for at least 6 months. A personal interview was carried out in all cases, during which the patients were questioned about adherence to treatment. Platelet thromboxane A2 synthesis was assessed in a single laboratory for the biochemical determination in all patients. Results: A total of 73 patients (mean age 67) were studied, with a mean duration of aspirin therapy of 25.4 months (range 6–144 months). Sixty-six patients (90.4%) were included in laboratory tests. All showed inhibition of thromboxane A2 synthesis, consistent with adherence to treatment. Conclusions: Aspirin compliance was found to be excellent. All the patients who presented themselves for laboratory tests were taking aspirin. Even if the patients who failed to show up for laboratory testing are regarded as noncompliants, at least 90% of all patients were compliants – in agreement with the findings of the recent literature. Personal interview plus biochemical determination of platelet thromboxane A2 synthesis seem adequate for assessing adherence to aspirin.
Early CT Findings in Unknown-Onset and Wake-Up Strokes
Authors: Todo Kenichi , Moriwaki Hiroshi , Saito Kozue , Tanaka Makiko , Oe Hiroshi , Naritomi Hiroaki
Published: February 2006

Background: Approximately one quarter of the acute ischemic stroke patients notice the event at awakening. Such patients with stroke at awakening are usually excluded from thrombolysis, since the time of stroke onset cannot be definitely identified. We compared the hyperacute CT findings of awakening stroke patients with those of stroke patients with known onset to assess whether the time of stroke onset is shortly before awakening. Methods: Subjects were cardioembolic stroke patients who were consecutively admitted to our department within 3 h after the recognition of stroke during the period between January 2000 and March 2003. The patients were classified into three groups: group A with stroke of known onset, group B with stroke at awakening, and group C with stroke of unknown onset due to lack of a witness. The clinical and CT findings in each group were compared. Results: A total of 81 patients fulfilled the study criteria. There were 46 patients in group A, 17 patients in group B, and 18 patients in group C. There was no significant difference in CT findings between groups A and B. In group C, however, definite hypodense areas were more commonly found than in group A (56 vs. 0%; p < 0.001) or in group B (56 vs. 11%; p = 0.012). Conclusion: Based on our CT findings, stroke at awakening seems to be developing shortly before in a large subset of patients, making them potential candidates for acute stroke therapies.
Secondary Prevention of Stroke in Patients with Atrial Fibrillation: Factors Influencing the Prescription of Oral Anticoagulation at Discharge
Authors: Deplanque Dominique , Leys Didier , Parnetti Lucilla , Schmidt Reinhold , Ferro Jose , de Reuck Jacques , Mas Jean-Louis , Gallai Virgilio
Published: February 2006

Background: Oral anticoagulation (OAC) is the only treatment that has shown a significant benefit to reduce the risk of recurrence in patients with ischemic stroke and nonvalvular atrial fibrillation (NVAF). However, OAC is still underused, even at discharge from neurological centers. The objective of this study was to identify the reasons underlying the prescription of OAC at discharge after an ischemic stroke in patients with NVAF. Methods: We investigated the reasons why ischemic stroke patients with NVAF were not treated with OAC at discharge from 40 centers located in 5 European countries (Austria, Belgium, France, Italy, and Portugal). Results: Of 320 ischemic stroke survivors at discharge, 186 (58.1%) received OAC, while 260 (81.3%) patients were theoretically eligible according to guidelines and the absence of contraindications. There were significant differences between countries and the logistic regression analysis found being already under OAC before stroke, having no leukoaraiosis, having no potential contraindication, being younger than 75 years, being married and suffering from angina pectoris as independent predictors of being discharged under OAC. Conclusion: This study suggests that besides patient-related factors, the prescription of OAC is also significantly influenced by the social environment and national practices.
Citicoline in Intracerebral Haemorrhage: A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre Pilot Study
Authors: Secades Julio J. , Ðlvarez-Sabín José , Rubio Francisco , Lozano Rafael , Dávalos Antoni , Castillo José
Published: February 2006

Background: In experimental models citicoline has shown beneficial effects in intracerebral haemorrhage. Citicoline is a neuroprotectant drug with some beneficial effects in human ischaemic stroke and with an excellent safety profile. We decided to carry out a pilot study to test its safety and efficacy in human intracerebral haemorrhaging. Methods: In this double-blind, placebo-controlled pilot study, patients had to be previously independent, aged between 40 and 85 years, and had to be admitted within 6 h after onset of symptoms of an acute primary supratentorial hemispheric cerebral haemorrhage diagnosed by neuroimaging (CT or MRI). Baseline severity was defined as patients with a score larger than 8 points on the Glasgow Coma Scale and larger than 7 on the National Institutes of Health Stroke Scale. Patients received either a placebo or 1 g/12 h citicoline for 2 weeks (orally or intravenously). The primary aim was to evaluate safety with respect to the number of adverse events that occurred. The efficacy endpoint was the percentage of patients with a modified Rankin Score (mRS) at 3 months. Results: 19 patients in each group were included in the study. The incidence of serious adverse events was not different among groups (4 patients in each group). One patient in the placebo group was categorised as independent (mRS ≤ 2) in comparison with 5 patients in the citicoline group (OR, 5.38; 95% CI, 0.55–52). Conclusions: Citicoline seems to be a safe drug in human intracerebral haemorrhage with a positive trend regarding efficacy. These data should be confirmed in a larger trial.
Improving Patient Selection for Clinical Acute Stroke Trials
Authors: Weimar Christian , Ho Tony W. , Katsarava Zaza , Diener Hans-Christoph
Published: February 2006

Objective: To optimize patient inclusion criteria for clinical acute stroke trials. Methods: We stratified probabilities of death and complete recovery based on two validated prognostic models using age and the National Institutes of Health Stroke Scale (NIH-SS) at admission. In an independent data set of 1,725 consecutively admitted patients with acute ischemic stroke, computer simulation with various inclusion thresholds was used to calculate the number and percentage of potential treatment responders, i.e. who had not died or spontaneously recovered. Results: Using defined thresholds for recovery and mortality, inclusion and exclusion criteria could be designed to considerably decrease both trial time and study size compared to a fixed inclusion criterion based on the NIH-SS alone. Other thresholds may allow optimization of either trial time or study size. Conclusions: The resulting models provide a validated approach for an efficient study inclusion of potential treatment responders based on the Barthel Index 100 days after ischemic stroke. These techniques provide the opportunity for improved stroke trials in terms of enrollment speed, treatment effect size or both.
Influence of Inflated Lung Pressure on Lung Mechanical Properties during Cold Storage in Rats
Authors: Ikeyama Kazuyuki , Sakai Hiroaki , Omasa Mitsugu , Hamakawa Hiroshi , Nakamura Takayuki , Fujinaga Takuji , Fukuse Tatsuo , Wada Hiromi
Published: February 2006

The degree of lung inflation pressure during cold storage has a deep connection with lung functions after reperfusion. However, the change of the lung mechanical properties during cold storage at the different lung inflation pressure is unknown. We investigated the change of the mechanical properties both at the organ and the tissue level under different inflated lung pressure soon after the cold storage. In group I, the lungs were not preserved. In group II, the lungs were preserved in deflated condition. In groups III and IV, the lungs were inflated with room air at pressures of 14 and 25 cm H2O. After 24-hour storage, the input impedance (Z) was measured by a computer-controlled small animal ventilator (n = 8 each group). All data were analyzed using a homogeneous linear model, which includes airway resistance (Raw), tissue elastance (H), and tissue damping (G). Hysteresivity (η) was calculated as G/H. After Z measurement, the tissue elasticity (Eqs) obtained from the quasi-static stress-strain curve was compared. We also analyzed the biochemical changes of surfactant in bronchoalveolar lavage (BAL) fluid. Raw was significantly lower in groups III and IV than in group I (p < 0.01). Hysteresivity (η) was significantly lower in group IV than in groups I and III (p < 0.05). Eqs was significantly higher in groups III and IV than in groups I and II (p < 0.01). The total protein level in the BAL fluid of the preserved groups was significantly higher compared with group I (p <0.01). We conclude that hyperinflated storage would deteriorate lung tissue mechanical properties.
Is There a Possibility for a Glutaraldehyde-Free Porcine Heart Valve to Grow?
Authors: Dohmen P.M. , da Costa F. , Holinski S. , Lopes S.V. , Yoshi S. , Reichert L.H. , Villani R. , Posner S. , Konertz W.
Published: February 2006

Objective: A challenging issue is to create a heart valve with growth and remodeling potential, which would be of great interest for congenital heart valve surgery. This study was performed to evaluate the growth and remodeling potentials of a decellularized heart valve. Methods: In 4 juvenile sheep (age 12 ± 1 weeks) with a weight of 24.3 ± 4.4 kg, a 17-mm diameter decellularized porcine valve was implanted as pulmonary valve replacement. Valve growth was evaluated by transthoracic echocardiography. At explantation, valves were evaluated by gross examination, light microscopy (hematoxylin and eosin, von Kossa, Sirius red, Weigert and Gomori staining), electron microscopy and immunohistochemistry. Atomic absorption spectrometry was performed to evaluate calcium content. Results: All animals showed fast recovery. The mean follow-up was 9.0 ± 1.8 months. All sheep at least doubled their weight (54.3 ± 9.2 kg). Echocardiography showed no regurgitation and a flow velocity of 0.7 ± 0.1 m/s at the latest follow-up. The valve diameter increased from 17.6 ± 0.5 to 27.5 ± 2.1 mm (p < 0.018). Gross examination showed a similar wall thickness of the implanted valve and native pulmonary wall, with smooth and pliable leaflets. Histology showed a monolayer of endothelial cells, fibroblast ingrowth and production of new collagen. No calcification was seen at von Kossa staining, confirmed by low calcium content levels of the valve wall and leaflets at atomic absorption spectrometry. Conclusions: This glutaraldehyde-free heart valve showed not only the absence of calcification, but also remodeling and growth potential.