bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruiting donors for autopsy based cancer research
Authors: Thombs J , Borthwick N J , Hungerford J L , Cree I A
Published: May 2005

The use of human tissue for scientific research is a highly sensitive issue. A lack of confidence in patient recruitment is one reason for the failure of many studies to be funded and it is important therefore that recruitment procedures are as effective and sympathetic as possible. The authors recruited patients with uveal melanoma into a postmortem study investigating tumour latency in this cancer. Two approaches were used—firstly a direct approach when patients attended clinic and secondly an initial approach by mail followed by telephone contact. In the first year of study the authors had a take up rate of 88.5%, significantly higher than the average rate of 40% quoted by the National Institute for Clinical Excellence (NICE). Key features are a sympathetic personal approach by experienced oncology nurses, the provision of clear information, and the inclusion of the next of kin in the recruitment procedure.
Smoking attributable mortality for Taiwan and its projection to 2020 under different smoking scenarios
Authors: Wen C P , Tsai S P , Chen C-J , Cheng T Y , Tsai M-C , Levy D T
Published: May 2005

Objectives:To estimate smoking attributable mortality (SAM) in Taiwan for the years 2001 through 2020 under scenarios of reductions in smoking rates by 0%, 2%, 4%, and 10% per year.

Method:The smoking attributable fraction (SAF) was used to calculate SAM from the risk experience in following up a large cohort (86 580 people) in Taiwan. Smoking rates were based on the 2001 National Health Interview Survey and other national surveys. An average 10 year lag was assumed between smoking rates and subsequent mortality.

Results:In 2001, 18 803 deaths, or 1 out of 4 deaths (27%), in middle aged men (35–69 years old) were attributable to smoking. SAM has been increasing and will continue to increase if smoking rates remain constant or even if reduced annually by 2%. SAM would begin to decrease only if rates were to be reduced by at least 4% a year.

Conclusions:The projected SAM in this study illustrates the seriousness of smoking caused mortality. Current efforts in tobacco control would lead to a progressive increase in SAM, unless efforts were doubled and smoking rates reduced by more than 4% a year. The urgency in requiring stronger tobacco control programmes to attenuate the staggering death tolls is compelling.
A New Modular Polyketide Synthase in the Erythromycin Producer Saccharopolyspora erythraea
Authors: Boakes Steven , Oliynyk Markiyan , Cortés Jesús , Böhm Ines , Rudd Brian A.M. , Revill W.Peter , Staunton Jim , Leadlay Peter F.
Published: May 2005

A previously unidentified set of genes encoding a modular polyketide synthase (PKS) has been sequenced in Saccharopolyspora erythraea, producer of the antibiotic erythromycin. This new PKS gene cluster (pke) contains four adjacent large open reading frames (ORFs) encoding eight extension modules, flanked by a number of other ORFs which can be plausibly assigned roles in polyketide biosynthesis. Disruption of the pke PKS genes gave S. erythraea mutant JC2::pSBKS6, whose growth characteristics and pattern of secondary metabolite production did not apparently differ from the parent strain under any of the growth conditions tested. However, the pke PKS loading module and individual pke acyltransferase domains were shown to be active when used in engineered hybrid PKSs, making it highly likely that under appropriate conditions these biosynthetic genes are indeed expressed and active, and synthesize a novel polyketide product.
Corynebacterium glutamicum Glyceraldehyde-3-Phosphate Dehydrogenase Isoforms with Opposite, ATP-Dependent Regulation
Authors: Omumasaba Crispinus A. , Okai Naoko , Inui Masayuki , Yukawa Hideaki
Published: May 2005

Corynebacterium glutamicum gapA and gapB encode glyceraldehyde-3-phosphate dehydrogenases (GAPDHs) that differ in molecular weight and activity in the presence of ATP. Comparative genome analysis revealed that GapA, the product of gapA, represented the canonical GAPDH that is highly conserved across the three major life forms. GapB, with an additional 110-residue-long sequence upstream of its GAPDH-specific domain, was homologous only to select microbial putative GAPDHs. Upon gene disruption, the initial growth rates of the wild-type, ΔgapA and ΔgapB strains on glucose (0.77, 0.00 and 0.76 h–1, respectively), lactate (0.20, 0.18 and 0.15 h–1, respectively), pyruvate (0.39, 0.29 and 0.20 h–1, respectively), and acetate (0.06, 0.06 and 0.04 h–1, respectively), implied that GapA was indispensable for growth on glucose, that GapB, but not GapA, affected early growth on acetate, and that GapB had a greater influence on growth under gluconeogenic conditions than GapA. The disruption of either gapA or gapB showed no significant effect on the transcription of any of the other gap cluster genes although it led to reduced triosephosphate isomerase (TPI) activities. Glycolytic GAPDH activity at low in vitro ATP concentrations was solely attributed to the 35.9-kDa GapA. At higher ATP concentrations, the same activity was attributed to the 51.2-kDa GapB. Both enzymes, however, exhibited similar NADP-dependent GAPDH activities at the higher ATP concentrations. In effect therefore, the GAPDH-catalyzed reaction at low ATP concentrations was irreversible, with all the glycolytic activity strictly NAD-dependent and attributed to GapA. At higher ATP concentrations, the reaction was reversible, with glycolytic activity NAD- or NADP-dependent and attributed to GapB, while gluconeogenic activity was attributable to both GapA and GapB.
An Esterase Gene from Lactobacillus casei Cotranscribed with Genes Encoding a Phosphoenolpyruvate:Sugar Phosphotransferase System and Regulated by a LevR-Like Activator and σ54 Factor
Authors: Yebra María J. , Viana Rosa , Monedero Vicente , Deutscher Josef , Pérez-Martínez Gaspar
Published: May 2005

A new esterase-encoding gene was found in the draft genome sequence of Lactobacillus casei BL23 (CECT5275). It is located in an operon together with genes encoding the EIIA, EIIB, EIIC, and EIID proteins of a mannose class phosphoenolpyruvate:sugar phosphotransferase system. After overproduction in Escherichia coli and purification, the esterase could hydrolyze acetyl sugars, hence the operon was named esu for esterase-sugar uptake genes. Upstream of the genes encoding the EII components (esuABCD) and the esterase (esuE), two genes transcribed in the opposite sense were found which encode a Bacillus subtilis LevR-like transcriptional activator (esuR) and a σ54-like transcriptional factor (rpoN). As compared with the wild-type strain, elevated fructose phosphorylation was detected in L. casei mutants constitutively expressing the esu operon. However, none of the many sugars tested could induce the esu operon. The fact that EsuE exhibits esterase activity on acetyl sugars suggests that this operon could be involved in the uptake and metabolism of esterified sugars. Expression of the esu operon is similar to that of the B. subtilis lev operon: it contains a –12,–24 consensus promoter typical of σ54-regulated genes, and EsuR and RpoN are essential for its transcription which is negatively regulated by EIIBEsu. The esuABCDE transcription unit represents the first σ54-regulated operon in lactobacilli. Furthermore, replacement of His852 in the phosphoenolpyruvate:sugar phosphotransferase system regulation domain II of EsuR with Ala indicated that the transcription activator function of EsuR is inhibited by EIIBEsu-mediated phosphorylation at His852.
Epidemiologic Study of the Predisposing Factors in Erythema toxicum neonatorum
Authors: Liu Chao , Feng Jie , Qu Rui , Zhou Hui , Ma Huiqun , Niu Xinwu , Dang Qianli , Zhang Xianqi , Tian Zhongwei
Published: May 2005

Background: Erythema toxicum neonatorum (ETN) is a very common disease, but its predisposing factors are still unknown. Objective: To determine the predisposing factors of ETN. Methods: Seven hundred and eighty-three neonates born in the same hospital during the same period were investigated, and the factors predisposing to ETN were evaluated in a case-control study. Results: (1) The incidence of ETN is about 43.68%, and it is significantly higher in males than in females (p < 0.001). (2) Term birth (p < 0.05), first-pregnancy birth (p < 0.001), the birth season (summer and autumn, p < 0.005), being fed with milk powder substitute or a mixed diet (p < 0.001) and vaginal delivery (p < 0.001) are the predisposing factors of ETN. (3) The severity of ETN in neonates born by vaginal delivery is significantly correlated with the total length of labor (p < 0.001). Conclusion: Our findings suggest that environmental factors play an important role in the onset of ETN.
Novel Application of Layered Expression Scanning for Proteomic Profiling of Plucked Hair Follicles
Authors: Traicoff June L. , Baibakov Galina , Biesecker Greg , Richardson Frank , Ramesh Arun , Galperin Mikhail M. , Iwata Kenneth K. , Knezevic Vladimir
Published: May 2005

Background: There is a need for a technology that can quantitatively assay multiple proteins from a single hair follicle while preserving the morphology of the follicle. For proteomic profiling, the technology should be less labor intensive, with a higher throughput, more quantitative and more reproducible than immunohistochemistry. Objective: To test the ability of a novel method, layered expression scanning of hair (LES-hair) to detect the levels and localization of proteins in plucked hair follicles. Methods: LES-hair was used to assay proteins in the plucked hair follicle. Results: LES-hair detected differential expression of proteins within discrete regions of the plucked hair follicle. These proteins included cleaved caspase 3, Ki-67 and the phosphorylated forms of c-Kit, epidermal growth factor receptor and vascular endothelial growth factor receptor. Conclusion: LES-hair provides a research tool for studying the basic biology of plucked hair follicles and has potential clinical applications such as monitoring treatment of alopecia or using plucked hair follicles as a surrogate tissue to monitor pharmacodynamic effects of targeted cancer therapies.
Quality of Life and Stigmatization Profile in a Cohort of Vitiligo Patients and Effect of the Use of Camouflage
Authors: Ongenae K. , Dierckxsens L. , Brochez L. , van Geel N. , Naeyaert J.M.
Published: May 2005

Background: Few studies have paid attention to the effects of treatment interventions on the psychosocial consequences of vitiligo. Objectives: To quantify and analyse the psychosocial benefit of the use of camouflage in vitiligo patients. Patients and Methods: 78 vitiligo patients completed the Dermatology Life Quality Index (DLQI) and an adapted stigmatization questionnaire, and 62 of them completed the DLQI after at least a 1-month use of camouflage. Results: The initial mean overall DLQI score (n = 78) is 6.9 (SD 5.6). The mean global stigmatization score is 38%. Disease extent and disease severity are strong predictors of the DLQI (p < 0.0001). Vitiligo on the face/head/neck substantially affects the DLQI, independently of degree of involvement. The mean DLQI score before and after use of camouflage (n = 62) is 7.3 (SD 5.6) and 5.9 (SD 5.2; p = 0.006). Mainly the high-scoring items ‘feelings of embarrassment and self consciousness’ and ‘choice of clothing’ improve. Predictors of improvement are higher DLQI scores (p = 0.0005) and higher total severity scores (p = 0.03). Conclusions: Camouflage can be recommended, particularly in patients with higher DLQI scores or self-assessed disease severity. Patients with minor involvement of the face benefit from camouflage.
Critical Appraisal of Reports on the Treatment of Perioral Dermatitis
Authors: Weber Klaus , Thurmayr Rudolf
Published: May 2005

Background: Presently, problems exist with the rationale of oral therapy and the nature and indication of topical and accompanying treatment of perioral dermatitis. Objective: Providing the basis to overcome these problems by a quality evaluation of treatment reports and assessment of the consistency of treatment experience. Methods: Sources were Medline (1964–2004), Embase (1966–2004), the Cochrane Central (1971–2004) and 526 ref erences of 3 textbooks, 2 recent reviews and 30 papers on perioral dermatitis. Thirty English and German articles were selected. These studies were evaluated according to principles of evidence-based medicine and related criteria. Evaluation of 28 papers was carried out by the authors and of our own 2 papers by 2 other reviewers. Consistency of results was qualitatively assessed by the authors. Results: There wereonly 2 therapeutic trials of medium-range quality. The other studies were of low quality. Consistency was noted concerning treatment with oral tetracycline (with 1 exception), discontinuation of topical corticosteroids and cosmetics and, to a lesser extent, regarding no therapy. There was inconsistency in respect to topical therapy. Conclusion: The presented data help to interpret and conduct studies on the treatment of perioral dermatitis.
Three Cases of Transition from Pemphigus vulgaris to Pemphigus foliaceus Confirmed by Desmoglein ELISA
Authors: Ng Patricia Pei Lin , Thng Steven Tien Guan
Published: May 2005

We report 3 cases of pemphigus vulgaris (PV) confirmed by histology and direct and indirect immunofluorescence that showed transition to pemphigus foliaceus (PF) 2–4 years from the time of disease onset. Desmoglein (Dsg) ELISA testing of the sera from these 3 patients in the later stages of their disease showed the presence of anti-Dsg1 antibodies and the absence of anti-Dsg3 antibodies. These patients were on prednisolone and immunosuppressives at the time the sera were tested, and it is unclear if the transition from PV to PF is a permanent one or whether it is due to preferential suppression of Dsg3 antibodies below a certain threshold. Previously reported cases of transition from PV to PF and PF to PV are summarized.
A Patient with Subclinical Oculocutaneous Albinism Type 2 Diagnosed on Getting Severely Sunburned
Authors: Kawai Masahiro , Suzuki Tamio , Ito Shiro , Inagaki Katsuhiko , Suzuki Noriyuki , Tomita Yasushi
Published: May 2005

P-gene-related oculocutaneous albinism (OCA2) is an autosomal recessive disorder. The phenotype is typically somewhat less severe than that of the tyrosinase-negative type (OCA1A). One of the mutations in the P gene, A481T, is associated with a mild phenotype, occasionally with no distinctive skin manifestations, which is called subclinical OCA. We present a Japanese patient having the A481T mutant allele in the P gene with subclinical oculocutaneous albinism diagnosed on getting severely sunburned. The A481T mutant allele is relatively common in the Caucasian population as well as in Japan, indicating that a number of subclinical patients of OCA2 might exist not only in Japan, but also all over the world.
Ichthyosiform Mycosis fungoides: Report of a Case Associated with IgA Nephropathy
Authors: Sato Madoka , Sohara Masaaki , Kitamura Yohei , Hatamochi Atsushi , Yamazaki Soji
Published: May 2005

We report a case of ichthyosiform mycosis fungoides (MF) associated with IgA nephropathy. Histological examination showed a dense atypical lymphocytic infiltrate admixed with epithelioid cells and giant cells in the dermis associated with the features of epidermotropism and folliculotropism. Reported cases of ichthyosiform MF are reviewed and histopathological characters of ichthyosiform MF are summarized. We suggest a histiocyte/dendritic-cell-rich infiltrate, or granulomatous features of infiltrate may be another characteristic of ichthyosiform MF. This case was associated with IgA nephropathy, which is uncommon. Such a presentation has never been reported in the literature.
Sclerodermic Linear Lupus Panniculitis: Report of Two Cases
Authors: Marzano A.V. , Tanzi C. , Caputo R. , Alessi E.
Published: May 2005

Lupus erythematosus panniculitis is a rare disease characterized by deep subcutaneous nodules, most commonly localized on the upper limbs and face. Unique clinical presentations, such as linear configuration or ‘overlap’ forms between lupus erythematosus panniculitis and localized scleroderma have been reported. We present here the clinical characteristics, course and laboratory findings of 2 patients having linear lupus erythematosus panniculitis with localized scleroderma-like changes. The 2 patients (of the 14 patients with lupus erythematosus panniculitis seen by us since 1990) were females with a young age at the onset of disease (median, 25 years). In 1 case, evolution into systemic lupus erythematosus with severe renal involvement occurred whereas the other patient, who had a spontaneous abortion and exhibited anticardiolipin antibodies, should be followed and screened for the emergence of antiphospholipid syndrome. Thus, the clinical behavior of this variant seems to be more aggressive, as compared with the usual course of lupus erythematosus panniculitis, which is considered to be a benign disease, although some reports have suggested that its prognosis is not always favorable. The linear distribution could be the clinical hallmark of such a unique, ‘sclerodermic’ subset of lupus erythematosus panniculitis.
Pseudocyst of the Scalp
Authors: Tsuruta Daisuke , Hayashi Akihide , Kobayashi Hiromi , Nakagawa Koichi , Furukawa Masayoshi , Ishii Masamitsu
Published: May 2005

We describe 4 cases of pseudocyst of the scalp, which still is only being described in the Japanese literature. The tumor is characterized as follows: localized between the top and the forehead area of the scalp, it first appears as a solitary reddish, painful small nodule or papule; it then gradually increases in size, protruding into a dome-shaped mass, and becomes associated with alopecia limited to the lesion area. This report describes typical cases of pseudocyst of the scalp, reviews the reported Japanese cases and introduces this tumor to western dermatology.
Cutaneous Manifestations as Presenting Sign of Autoimmune Lymphoproliferative Syndrome in Childhood
Authors: Auricchio Luigi , Vitiello Laura , Adriani Marsilio , Ferri Pasqualina , Chiocchetti Annalisa , Pettinato Guido , Racioppi Luigi , Maiuri Luigi , Dianzani Umberto , Pignata Claudio
Published: May 2005

Autoimmune lymphoproliferative syndrome is a disorder due to a defect of lymphocyte apoptosis, whose clinical manifestations consist of hyperplasia of lymphoid tissues and autoimmune diseases. We report on a 26-month-old child who presented with frequent eruptions of weals and angioedema without any apparent triggering factor, who subsequently developed an erythematopapular rash with a histological pattern of a lymphoplasmacellular infiltrate. Familial anamnesis revealed a history of lymphoadenomegaly and massive spleen and liver enlargement in her sister. Functional and molecular analysis led to a diagnosis of type 1a autoimmune lymphoproliferative syndrome. Immunophenotyping of the cutaneous lesion revealed the presence of an inflammatory infiltrate with a considerably high number of Langerhans cells. Cutaneous features such as urticaria, angioedema and vasculitis in children with a personal and familial history of hyperplasia of lymphoid tissues may be a presenting sign of a systemic disease, such as autoimmune lymphoproliferative syndrome.
Drug-Induced Hypersensitivity Syndrome Associated with Transient Hypogammaglobulinaemia and Increase in Serum IgE Level
Authors: Nakashima H. , Yamane K. , Ihn H. , Nakamura K. , Watanabe R. , Kuwano Y. , Takekoshi T. , Watanabe T. , Hattori N. , Fujimoto M. , Tamaki K.
Published: May 2005

Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disease with multiorgan failure. Recently, the association of the human herpesvirus (HHV) family, particularly of HHV-6, with DIHS has been reported. We report a 43-year-old female diagnosed as having DIHS based on the clinical course and laboratory examinations. The HHV-6 reactivation was demonstrated by significantly increased levels of the specific antibody in her paired sera and by polymerase chain reaction of HHV-6 DNA. Notably, transient hypogammaglobulinaemia was detected in the early stage of the disease, which was associated with the disease activity. By contrast, the serum IgE level and eosinophils were increased 2 or 3 weeks later. In addition, serum levels of interferon γ, interleukin (IL)-4 and soluble IL-2 receptor, which were increased in the early phase of the disease, decreased gradually after the corticosteroid therapy.
Economic Evaluation of Prenatal Population Screening for Fragile X Syndrome
Authors: Hollingsworth Bruce , Harris Anthony
Published: May 2005

Objectives: This paper models costs and benefits of a population screening programme for pregnant women to detect fragile X syndrome. Given the high lifetime costs of fragile X and the high sensitivity and specificity of testing, such a programme may seem attractive. Methods: Economic evaluation. Results: Our base case results indicate that such a programme seems close to cost neutral, so may indeed seem attractive for this reason. However, sensitivity analysis shows that assumptions regarding lifetime costs are crucial to results; our results suggest if lifetime costs are under AUD 2.5 million, costs of screening will exceed future costs avoided. Conclusions: Economic modelling of screening programmes reveals valuable information which might have an influence on the debate on the social value of a population screening programme for fragile X in pregnant women.
Thromboembolic Prophylaxis with Fondaparinux in Major Orthopaedic Surgery: Outcomes and Costs
Authors: Szucs Thomas D. , Kaiser Walter E. , Mahler Felix , Gutzwiller Felix
Published: May 2005

Objective: To compare economic impacts of anti-thromboembolism prophylaxis with two medications – new pentasaccharide fondaparinux versus low molecular weight heparin (LMWH) – in major orthopaedic surgery, such as hip and knee replacement and hip fracture repair, in Switzerland. In order to meet this objective, three parameters were determined for an observation period of 5 years. (1) Outcomes: Frequency of deep vein thrombosis (DVT), pulmonary embolism (PE) and their complications. (2) Cost burden of disease: Determination of the costs of DVT, PE and complications not prevented despite prophylaxis. (3) Total costs of prophylaxis: Costs were calculated from the perspective of the health insurance scheme. Methods: In order to determine outcomes and cost burden of disease, a model was applied which generates the post-surgery course of thromboembolic events (TE) and their complications for individual cohorts of patients undergoing hip and knee replacement surgery and hip fracture repair. These findings were allocated to the Swiss standard diagnostic and therapeutic measures (resource consumption), which enabled subsequent calculation of the costs of TE, including complications not prevented in spite of prophylaxis (cost burden of disease) based on standard Swiss tariffs. Additionally, total costs of prophylaxis, including costs of medications and monitoring, were determined. Results: In Switzerland, the following outcomes (expressed as percentage of the number of patients undergoing surgery) can be expected for TE prophylaxis with LMWH and with fondaparinux: DVT 3.4 vs. 2.3%, PE 1.4 vs. 0.7%, recurrent DVT 0.2 vs. 0.1%, post-thrombotic syndrome 4.8 vs. 3.5%. The costs of non-prevented TE and their complications add up to CHF 437 vs. CHF 306 per patient undergoing major orthopaedic surgery; the total cost burden for Switzerland amounts to CHF 13.4 million vs. CHF 9.4 million (30% less). Thus, despite higher medication costs, the use of fondaparinux instead of LMWH saves a total of CHF 105 per operated patient from the perspective of the health insurer. Conclusion: Fondaparinux is superior to LMWH in regards to both clinical efficacy and financial costs. This statement is confirmed by sensitivity analysis with different parameters over a broad range.
Effect of Genotyping Error on Type-I Error Rate of Affected Sib Pair Studies with Genotyped Parents
Authors: Seaman S.R. , Holmans P.
Published: May 2005

Objective: In affected sib pair studies without genotyped parents the effect of genotyping error is generally to reduce the type I error rate and power of tests for linkage. The effect of genotyping error when parents have been genotyped is unknown. We investigated the type I error rate of the single-point Mean test for studies in which genotypes of both parents are available. Methods: Datasets were simulated assuming no linkage and one of five models for genotyping error. In each dataset, Mendelian-inconsistent families were either excluded or regenotyped, and then the Mean test applied. Results: We found that genotyping errors lead to an inflated type I error rate when inconsistent families are excluded. Depending on the genotyping-error model assumed, regenotyping inconsistent families has one of several effects. It may produce the same type I error rate as if inconsistent families are excluded; it may reduce the type I error, but still leave an anti-conservative test; or it may give a conservative test. Departures of the type I error rate from its nominal level increase with both the genotyping error rate and sample size. Conclusion: We recommend that markers with high error rates either be excluded from the analysis or be regenotyped in all families.
Regulation of Vascular Tone from Spontaneously Hypertensive Rats by the HMG-CoA Reductase Inhibitor, Simvastatin
Authors: Pérez-Guerrero Concepción , Márquez-Martín Ana , Herrera Maria Dolores , Marhuenda Elisa , Álvarez de Sotomayor María
Published: May 2005

The acute effect of simvastatin on aortic rings from spontaneously hypertensive rats (SHRs) was identified. Simvastatin-evoked relaxations of both depolarized and phenylephrine-precontracted arteries were independent of the presence of endothelium. This effect was inhibited by diltiazem and mevalonate, but not by the Rho-kinase inhibitor, Y-27632. Simvastatin prevented contraction induced by phenylephrine, calcium ionophore A-23187 and CaCl2 in Ca2+-free medium. Y-27632 decreased the effect of simvastatin. On the contrary, contraction induced by noradrenaline in Ca2+-free medium was not affected. These results suggest that simvastatin elicited an effect on vascular smooth muscle cells from SHRs that may involve blockade of extracellular calcium entry and decrease vascular contraction by affecting Rho-kinase.
The Stacked ABR: A Sensitive and Specific Screening Tool for Detecting Small Acoustic Tumors
Authors: Don Manuel , Kwong Betty , Tanaka Chiemi , Brackmann Derald , Nelson Ralph
Published: May 2005

The failure of standard ABR measures to detect small (≤1 cm) acoustic tumors has led to the use of enhanced magnetic resonance imaging (MRI) as the standard to screen for small tumors. This study investigates the suitability of the stacked ABR as a sensitive screening alternative to MRI for small acoustic tumors (SATs). The objective of the study was to determine the sensitivity and specificity of the stacked ABR technique for detecting SATs. A total of 54 patients with acoustic tumors identified by MRI that were either ≤1 cm in size or undetected by standard ABR methods, irrespective of size, were studied. A control population of 78 nontumor normal-hearing subjects was also tested. For comparison, two standard ABR measures (IT5 and I-V delay) were also analyzed. The stacked ABR demonstrated 95% sensitivity and 88% specificity; 100% sensitivity was obtained at 50% specificity. Standard ABR measures were much poorer in detecting these tumors. In conclusion, the stacked ABR can be used as a sensitive, widely-available, cost-effective, and comfortable tool for screening SATs.
Effects of cGMP on Coordination of Vascular Smooth Muscle Cells of Rat Mesenteric Small Arteries
Authors: Rahman Awahan , Matchkov Vladimir , Nilsson Holger , Aalkjær Christian
Published: May 2005

Objective: We tested the hypothesis that cGMP can induce a state of only partial coordination of vascular smooth muscle cells (VSMC). Methods: This was done by studying the concentration-dependent effect of 8Br-cGMP on isometric and isobaric force development of noradrenaline-activated segments of rat mesenteric small arteries in which the endothelium was removed. We further measured the concentration-dependent effect of 8Br-cGMP on VSMC membrane potential, spatially resolved [Ca2+]i and VSMC membrane conductance. Results: With 300 µM 8Br-cGMP, coordinated [Ca2+]i activity and vasomotion were seen as previously reported. At 10–30 µM 8Br-cGMP, beating isometric tension oscillations were seen. Isobaric recordings revealed oscillations with different frequencies in different parts of the arteries. At these (10–30 µM) 8Br-cGMP concentrations, membrane potential oscillations did not always concur with isometric tension oscillations, and [Ca2+]i oscillations were only synchronized locally within groups of cells. 8Br-cGMP concentration-dependently decreased the frequency of vasomotion and, in unsynchronized hyperpolarized VSMC, the frequency of [Ca2+]i waves. Conclusion: Our results demonstrated that cGMP can cause a partial coordination of the VSMC in the vascular wall (and at high concentrations near complete coordination). Furthermore, the cGMP concentration-dependent decrease of Ca2+ wave frequency and of vasomotion frequency suggests that cGMP modifies oscillatory Ca2+ release from the sarcoplasmic reticulum and supports the suggestion that this oscillatory release paces vasomotion.
Fimbrio-Ovarian Relationship in Unexplained Infertility
Authors: Roy Kallol Kumar , Hegde Prashanth , Banerjee Kaberi , Malhotra Neena , Nayyar Bonilla , Deka Deepika , Kumar Sunesh
Published: May 2005

Introduction: The role of defective fimbrio-ovarian relation in cases of unexplained infertility has not been extensively studied. The aim of the study was to assess the role of fimbrio-ovarian relation as an investigative modality in women with unexplained infertility. We also aimed to evaluate the efficacy of superovulation and freeing the fimbria-ovarica in increasing the conception rate of women with unexplained infertility. Materials and Methods: This was a prospective study where out of 80 infertile couples, 19 women with unexplained infertility were recruited as study group. Fifteen fertile women were recruited as control group. During laparoscopy the length of the fimbria-ovarica and the ovulation border was measured. The fimbrio-ovarian accessibility test was demonstrated by holding the tubal fimbria by a non-traumatizing grasper and their ability to reach or cover the ovulation site. The freeing of the fimbria-ovarica was done, if its length was less than 2 cm. All cases were given ovulation induction for consecutive six cycles and were followed up to document any conception. Results: The mean length of the fimbria-ovarica was significantly less in patients with unexplained infertility (2.5 ± 0.6 vs. 3.55 ± 0.8 cm). The mean length of the ovulation border was not significantly different in cases and controls (2.95 ± 0.6 vs. 3.55 ± 0.5 cm). The fimbrio-ovarian accessibility test was positive in 6 (31.5%) cases and in 14 (93%) controls. The fimbrio-ovarian accessibility test was negative in 13 (68.4%) cases and in 1 (7%) control. Out of the 13 cases with negative FOAT, 7 had fimbrial length less than 2 cm and in whom the freeing of fimbria-ovarica was done because of severe resistance during stretching. Out of 7 patients in whom freeing of fimbria-ovarica was done 3 conceived (42.8%). Out of the 12 patients who got only ovulation induction 3 conceived (25%). Conclusion: Fimbrio-ovarian accessibility test appears to be a promising investigative modality to assess ovarian pick-up in patients with unexplained infertility. Correcting fimbrio-ovarian relation (freeing short fimbria-ovarica) improves pregnancy rate in women with unexplained infertility.
Antiinflammatory Effects of Tetradecylthioacetic Acid Involve Both Peroxisome Proliferator–Activated Receptor α–Dependent and –Independent Pathways
Authors: Dyrøy Endre , Yndestad Arne , Ueland Thor , Halvorsen Bente , Damås Jan Kristian , Aukrust Pål , Berge Rolf K.
Published: May 2005

Objective—

Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator–activated receptors (PPARs). Human endothelial cells express PPARs. We hypothesized that TTA could modulate endothelial cell activation at least partly through PPAR-related mechanisms.

Methods and Results—

We explored this hypothesis by different experimental approaches involving both in vitro studies in human endothelial cells (HUVECs) and in vivo studies in humans and PPAR-α
−/−
mice. Our main findings were as follows: (1) TTA suppressed the tumor necrosis factor α–induced expression of vascular cell adhesion molecule 1 (VCAM-1) and interleukin 8 (IL-8) in HUVECs. (2) No TTA-mediated attenuation of VCAM-1 and chemokine expression was seen in the liver of PPAR-α
−/−
mice. (3) Whereas TTA markedly enhanced PPAR-α–target genes in the liver of wild-type, but not of PPAR-α
−/−
, mice, no such effect on PPAR-α–target genes was seen in HUVECs. (4) The relevance of our findings to human disease was suggested by a TTA-mediated downregulation of serum levels of soluble VCAM-1 and IL-8 in psoriasis patients.

Conclusion—

We show that TTA has the ability to attenuate tumor necrosis factor α–mediated endothelial cell activation, further supporting antiinflammatory effects of this fatty acid, possibly involving both PPAR-α–dependent and –independent pathways.
Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression
Authors: Chauveau Christine , Rémy Séverine , Royer Pierre Joseph , Hill Marcelo , Tanguy-Royer Séverine , Hubert François-Xavier , Tesson Laurent , Brion Régis , Beriou Gaëlle , Gregoire Marc , Josien Régis , Cuturi Maria Cristina , Anegon Ignacio
Published: May 2005

Heme oxygenase-1 (HO-1) is an intracellular enzyme that degrades heme and inhibits immune responses and inflammation in vivo. In most cell types, HO-1 is inducible by inflammatory stimuli and oxidative stress. Here we demonstrate that human monocyte-derived immature dendritic cells (iDCs) and several but not all freshly isolated rat splenic DC subsets and rat bone marrow-derived iDCs, spontaneously express HO-1. HO-1 expression drastically decreases during human and rat DC maturation induced in vitro. In human tissues, iDCs also express HO-1, whereas mature DCs do not. Induction of HO-1 expression with cobalt protoporphyrin (CoPP) in human and rat DCs inhibits lipopolysaccharide (LPS)-induced phenotypic maturation and secretion of proinflammatory cytokines, resulting in the inhibition of alloreactive T-cell proliferation. CoPP-treated DCs, however, retain the ability to produce the anti-inflammatory cytokine interleukin 10 (IL-10). Reactive oxygen species induced by LPS in DCs were inhibited by induction of HO-1. In conclusion, we identify, for the first time, the capacity of HO-1 to block maturation of DCs and to inhibit proinflammatory and allogeneic immune responses while preserving IL-10 production. This novel immune function for HO-1 may be of interest for the inhibition of immune responses in autoimmune diseases, transplantation, and other conditions involving activation of the immune system. (Blood. 2005;106:1694-1702)
Clinical presentation of pertussis in fully immunized children in Lithuania
Authors: Narkeviciute Irena , Kavaliunaite Ema , Bernatoniene Genovaite , Eidukevicius Rimantas
Published: May 2005

Background

In Lithuania, the vaccination coverage against pertussis is high. Nevertheless, there is a significant increase in pertussis cases in fully immunized children. The aim of our study was to determine the frequency of classical symptoms of laboratory confirmed pertussis and describe its epidemiology in children fully vaccinated against pertussis.

Methods

From May to December 2001, 70 children aged 1 month to 15 years, suffering from prolonged cough were investigated in the Centre of Paediatrics, Vilnius University Children's Hospital. The collected information included personal data, vaccination history, clinical symptoms of the current illness, and treatment before hospitalization. At the admission to the hospital blood samples were taken from all studied children for Bordetella pertussis IgM and IgA.

Results

A total of 53 (75.7%) of the 70 recruited patients with prolonged cough showed laboratory evidence of pertussis. 32 of them were fully vaccinated with whole cell pertussis vaccine (DTP). The age of fully vaccinated patients varied from 4 to 15 years (average 10.9 ± 3.1; median 11). The time period between the last vaccination dose (fourth) and the clinical manifestation of pertussis was 2.6–13 years (average 8.9 ± 3.0; median 9). More than half of the children before the beginning of pertussis were in contact with persons suffering from long lasting cough illness in the family, school or day-care center. The mean duration from onset of pertussis symptoms until hospitalization was 61.4 ± 68.3 days (range, 7 to 270 days; median 30). For 11 patients who had had two episodes (waves) of coughing, the median duration of cough was 90 days, and for 21 with one episode 30 days (p < 0.0002). Most of the children (84.4%) had paroxysmal cough, 31.3% had post-tussive vomiting, 28.1% typical whoop, and 3.1% apnea. Only 15.6% children had atypical symptoms of pertussis.

Conclusion

Fully vaccinated children fell ill with pertussis at the median of 11 years old, 9 years following pertussis vaccination. More than half of the children could catch pertussis at home, at school or day-care center. Clinical picture of pertussis in previously immunized children is usually characterized by such classical symptoms as prolonged and paroxysmal cough, rarely by whopping and post-tussive vomiting, and very rarely by apnea.
Effect of Cr(V) on reproductive organ morphology and sperm parameters: An experimental study in mice
Authors: Pereira Maria de Lourdes , das Neves Ricardo Pires , Oliveira Helena , Santos Teresa Margarida , de Jesus Júlio Pedrosa
Published: May 2005

Background

Cr(V) species are formed during the intracellular reduction of Cr(VI), a ubiquitous environmental pollutant. In this study, the acute toxicity of a physiologically stable Cr(V) compound, [CrV-BT]2- (BT = bis(hydroxyethyl)aminotris(hydroxymethyl)methane) was investigated in the male reproductive system of sexually mature 60-day-old male ICR-CD1 mice.

Methods

Eight-week-old animals were subcutaneously injected daily with a dose of ca 8 μmol of Cr/mouse, during 5 days. The control group was injected with 0.5 mL of BT buffer. Testis and epididymis morphology was evaluated using light and transmission electron microscopy. Epididymal sperm counts, motility and acrosome integrity were also assayed using standard methods.

Results

Seminiferous epithelium abnormalities were detected in the CrV-BT experimental group, including intraepithelial vacuolation, and remarkable degeneration of Sertoli cells, spermatocytes and spermatids. The premature release of germ cells into the tubular lumen was also evident. Histological evaluation of epididymal compartments revealed apparently normal features. However, the epididymal epithelium presented vacuolation. [CrV-BT]2- induced a reduction in sperm acrosome integrity. However, sperm motility and density were not significantly affected.

Conclusion

This in vivo study using a Cr(V) compound, provides evidence for the potential reproductive hazards caused on male reproductive system by species containing chromium in intermediate oxidation states.
Duration of bed occupancy as calculated at a random chosen day in an acute care ward. Implications for the use of scarce resources in psychiatric care
Authors: Berg John E , Restan Asbjørn
Published: May 2005

Background

Psychiatric acute wards are obliged to admit patients without delay according to the Act on Compulsive Psychiatric Care. Residential long term treatment facilities and rehabilitation facilities may use a waiting list. Patients, who may not be discharged from the acute ward or should not wait there, then occupy acute ward beds.

Materials and methods

Bed occupancy in one acute ward at a random day in 2002 was registered (n = 23). Successively, the length of stay of all patients was registered, together with information on waiting time after a decision was made on further treatment needs. Eleven patients waited for further resident treatment. The running cost of stay was calculated for the acute ward and in the different resident follow-up facilities. Twenty-three patients consumed a total of 776 resident days. 425 (54.8%) of these were waiting days. Patients waited up to 86 days.

Results

Total cost of treatment was 0.69 million Euro (0.90 mill. $), waiting costs were 54.8% of this, 0.38 million Euro (0.50 million $). The difference between acute care costs and the costs in the relevant secondary resident facility was defined as the imputed loss. Net loss by waiting was 0.20 million Euro (0.26 million $) or 28.8% of total cost.

Discussion

This point estimate study indicates that treating patients too sick to be released to anything less than some other intramural facility locks a sizable amount of the resources of a psychiatric acute ward. The method used minimized the chance of financially biased treatment decisions. Costs of frustration to staff and family members, and delayed effect of treatment was set to zero. Direct extrapolation to costs per year is not warranted, but it is suggested that our findings would be comparable to other acute wards as well. The study shows how participant observation and cost effectiveness analysis may be combined.
2-(18F)-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Detects Clinical Relevant Adenomas of the Colon: A Prospective Study
Authors: van Kouwen Mariëtte C.A. , Nagengast Fokko M. , Jansen Jan B.M.J. , Oyen Wim J.G. , Drenth Joost P.H.
Published: May 2005

Purpose

2-(18F)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is a noninvasive imaging technique used clinically to detect malignant tumors. FDG-PET has been established as a tool for diagnosis of recurrent or metastatic colorectal carcinoma. Several case series suggest that FDG-PET also detects larger adenomas. The goal of this study was to investigate whether FDG-PET is able to detect colonic adenomas.

Patients and Methods

FDG-PET was performed in 100 consecutive patients in whom colonic adenomas were suspected on barium enema (n = 47) or sigmoidoscopy (n = 53). A positive scan was defined as focal large bowel FDG accumulation. FDG-PET was followed in all cases by colonoscopy, and removed adenomas were examined histopathologically.

Results

Colonoscopy confirmed the presence of adenomas in 68 of 100 patients. In 35 patients, there was focal FDG accumulation at site of the adenoma. The sensitivity of FDG-PET increased with adenoma size (21%, adenomas 1 to 5 mm; 47%, 6 to 10 mm; and 72%, > 11 mm). The sensitivity of FDG-PET also increased with the grade of dysplasia (33%, low grade; 76%, high grade; and 89%, carcinomas). The overall specificity was 84%.

Conclusion

FDG-PET detects colonic adenomas and the diagnostic test characteristics improve with size and grade of dysplasia of the adenoma.
Randomized Phase III Intergroup Trial of Etoposide and Cisplatin With or Without Paclitaxel and Granulocyte Colony-Stimulating Factor in Patients With Extensive-Stage Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 9732
Authors: Niell Harvey B. , Herndon James E. , Miller Antonius A. , Watson Dorothy M. , Sandler Alan B. , Kelly Karen , Marks Randolph S. , Perry Micheal C. , Ansari Rafat H. , Otterson Grefory , Ellerton John , Vokes Everett E. , Green Mark R.
Published: May 2005

Purpose

To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity.

Patients and Methods

Eligible patients (N = 587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET).

Results

Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET.

Conclusion

PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.
Successful Implementation of the Randomized Discontinuation Trial Design: An Application to the Study of the Putative Antiangiogenic Agent Carboxyaminoimidazole in Renal Cell Carcinoma—CALGB 69901
Authors: Stadler Walter M. , Rosner Gary , Small Eric , Hollis Donna , Rini Brian , Zaentz S. Donald , Mahoney John , Ratain Mark J.
Published: May 2005

Purpose

To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design.

Patients and Methods

Recruited patients had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week evaluation point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end point was the stable disease rate in the randomized groups.

Results

A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatening toxicity was experienced by 34%, with asthenia (15%) and neuropsychiatric difficulties (7%) being most common. At the randomization point, 51% of patients had progressed, 30% withdrew, 1% experienced a partial response, and 17% had stable disease and were randomly assigned. A Bayesian futility analysis utilizing the first 49 randomly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9% even under the most optimistic a priori assumptions, and further trial accrual was halted.

Conclusion

CAI is inactive in RCC. The RDT design should be further explored for evaluating activity of putative disease stabilizing agents.