bluuebunny/crossref_metadata_2025 huggingface dataset:
Heme Oxygenase 1 in Cerebrospinal Fluid from Infants and Children after Severe Traumatic Brain Injury
Authors: Cousar J’mir L. , Lai Yichen , Marco Christina D. , Bayır Hülya , Adelson P. David , Janesko-Feldman Keri L. , Kochanek Patrick M. , Clark Robert S.B.
Published: August 2006

Heme oxygenase 1 (HO-1) is an enzyme important in the catabolism of heme that is induced under conditions of oxidative stress. HO-1 degradation of heme yields biliverdin, bilirubin, carbon monoxide and iron. HO-1 is thought to serve a protective antioxidant function, and upregulation of HO-1 has been demonstrated in experimental models of neurodegeneration, subarachnoid hemorrhage, cerebral ischemia and traumatic brain injury (TBI). We measured HO-1 concentration in cerebral spinal fluid samples from 48 infants and children following TBI and 7 control patients by ELISA. Increased HO-1 was seen in TBI versus control patients – mean 2.75 ± 0.63, peak 4.17 ± 0.96 ng/ml versus control (<0.078 ng/ml, not detectable) (p< 0.001). Increased HO-1 concentration was associated with increased injury severity and unfavorable neurological outcome (both p < 0.05). Increased HO-1 concentration was independently associated with younger age; however, statistical analysis could not rule out the possibility that the effect of age was related to inflicted TBI from child abuse. HO-1 increases after TBI and appears to be more prominent in infants compared with older children after injury.
Predicting Unconsciousness from a Pediatric Brain Injury Threshold
Authors: Zhu Qiliang , Prange Michael , Margulies Susan
Published: August 2006

The objective of this study was to utilize tissue deformation thresholds associated with acute axonal injury in the immature brain to predict the duration of unconsciousness. Ten anesthetized 3- to 5-day-old piglets were subjected to nonimpact axial rotations (110–260 rad/s) producing graded injury, with periods of unconsciousness from 0 to 80 min. Coronal sections of the perfusion-fixed brain were immunostained with neurofilament antibody (NF-68) and examined microscopically to identify regions of swollen axons and terminal retraction balls. Each experiment was simulated with a finite element computational model of the piglet brain and the recorded head velocity traces to estimate the local tissue deformation (strain), the strain rate and their product. Using thresholds associated with 50, 80 and 90% probability of axonal injury, white matter regions experiencing suprathreshold responses were determined and expressed as a fraction of the total white matter volume. These volume fractions were then correlated with the duration of unconsciousness, assuming a linear relationship. The thresholds for 80 and 90% probability of predicting injury were found to correlate better with injury severity than those for 50%, and the product of strain and strain rate was the best predictor of injury severity (p = 0.02). Predictive capacity of the linear relationship was confirmed with additional (n = 13) animal experiments. We conclude that the suprathreshold injured volume can provide a satisfactory prediction of injury severity in the immature brain.
Oxidative Stress in Immature Brain after Traumatic Brain Injury
Authors: Bayır Hülya , Kochanek Patrick M. , Kagan Valerian E.
Published: August 2006

High oxygen demand along with the abundance of readily oxidizable substrates yielding productive oxidative metabolism are required for the normal function of the brain. This necessitates the existence of the complex and multicomponent antioxidant system in the brain for protection against oxidative damage. However, during development, individual components of the antioxidant system are not equally expressed and not always sufficient to fulfill their tasks in a coordinated way. As a result, the developing brain may be more vulnerable to oxidative insults than the adult brain. Traumatic brain injury is one of the damaging acute impacts that challenge the brain antioxidant reserves by exposing them to a number of decompartmentalized prooxidant molecules. This review focuses on the sources and assessment of oxidative stress and the link between oxidative stress and cell death pathways in the immature brain after experimental and clinical traumatic brain injury.
Alpha-II-Spectrin after Controlled Cortical Impact in the Immature Rat Brain
Authors: Aikman J. , O’Steen B. , Silver X. , Torres R. , Boslaugh S. , Blackband S. , Padgett K. , Wang K.K.W. , Hayes R. , Pineda J.
Published: August 2006

Proteolytic processing plays an important role in regulating a wide range of important cellular functions, including processing of cytoskeletal proteins. Loss of cytoskeletal proteins such as spectrin is an important characteristic in a variety of acute central nervous system injuries including ischemia, spinal cord injury and traumatic brain injury (TBI). The literature contains extensive information on the proteolytic degradation of alpha-II-spectrin after TBI in the adult brain. By contrast, there is limited knowledge on the characteristics and relevance of these important processes in the immature brain. The present experiments examine TBI-induced proteolytic processing of alpha-II-spectrin after TBI in the immature rat brain. Distinct proteolytic products resulting from the degradation of the cytoskeletal protein alpha-II-spectrin by calpain and caspase 3 were readily detectable in cortical brain parenchyma and cerebrospinal fluid after TBI in immature rats.
Regionally Distinct Patterns of Calpain Activation and Traumatic Axonal Injury following Contusive Brain Injury in Immature Rats
Authors: Huh Jimmy W. , Franklin Michael A. , Widing Ashley G. , Raghupathi Ramesh
Published: August 2006

Impact-induced head injury in infants results in acute focal contusions and traumatic axonal injury (TAI) that are associated with chronic holohemispheric cortical and white matter atrophy and may contribute to poor outcome in brain-injured children less than 4 years of age. Contusive brain trauma in postnatal day (PND) 11 or PND 17 rat pups, ages neurologically equivalent to a human infant and toddler, respectively, leads to cortical tissue loss and white matter atrophy which are associated with cognitive deficits. In adult models of brain trauma and in brain-injured humans, acute and sustained activation of the calpain family of calcium-activated neutral proteases has been implicated in neuronal death and TAI. PND 11 or PND 17 rat pups were subjected to closed head injury over the left hemisphere using the controlled cortical impact device and sacrificed at 6 h, 24 h or 3 days. Hemorrhagic contusions and tissue tears in the cortex and white matter were visible at 6 h, and neuronal loss was evident by 3 days. Calpain activation was observed in cell soma and dendrites of injured neurons at 6 h, and in degenerating dendrites and atrophic neurons at 24 h after injury at both ages. Axonal accumulation of amyloid precursor protein, indicative of TAI, was observed in the corpus callosum and lateral aspects of the white matter below the site of impact, and in the thalamus in PND 11 rats only. Intra-axonal calpain activation was observed to a limited extent in the corpus callosum and subcortical white matter tracts in both brain-injured PND 11 and PND 17 rats. Collectively, these results provide evidence that calpain activation may participate in neuronal loss in the injured cortex, but may not contribute to the pathogenesis of TAI following contusive brain trauma in the immature rat.
Traffic Dynamics in Scale-Free Networks
Authors: Fekete Attila , Vattay Gábor , Kocarev Ljupco
Published: August 2006

We study traffic dynamics in growing scale-free networks. Both the scale-free structure of the network and the adaptive nature of the dynamics which controls traffic in the network are considered in the model. The model is investigated with computer simulations and analytically for the case of a scale-free tree. For the scale-free tree, an exact formula and its power law approximation of the complementary cumulative distribution function of link load (edge betweenness) is presented. We examine whether the scaling properties of the network affect the performance of the transport mechanism and estimate the average number of competing transport mechanisms at bottlenecks. We find that bottlenecks tend to appear on the periphery of the network as the performance increases. Various bandwidth allocation strategies are compared. We show that the best performance is achieved when capacity is distributed proportionally to the expected load of links. We demonstrate that it is necessary to study both the topology and the dynamics of the transport mechanism to understand the whole system.
Spreading on Networks: A Topographic View
Authors: Canright Geoffrey S. , Engø-Monsen Kenth
Published: August 2006

We apply our previously developed method of ‘topographic’ analysis of networks to the problem of epidemic spreading. We consider the simplest form of epidemic spreading, namely the ‘SI’ model. We argue that the eigenvector centrality of a node is a good indicator of that node’s spreading power. From this we develop seven specific predictions. In particular, we predict that each region (as defined by our approach) will have its own S curve for cumulative adoption over time, and we describe the various phases of the S curve in terms of motion of the infection over the region. Our predictions are well supported by simulations. In particular, the significance of regions to epidemic spreading is clear. Finally, we develop a mathematical theory, giving partial support to our picture. The theory includes a precise quantitative definition of the spreading power of a node, and some approximate analytical results for epidemic spreading.
Lightweight Centrality Measures in Networks under Attack
Authors: Georgiadis Giorgos , Kirousis Lefteris
Published: August 2006

In this paper we study deliberate attacks on the infrastructure of large scale-free networks. These attacks are based on the importance of individual vertices in the network in order to be successful, and the concept of centrality (originating from social science) has already been utilized in their study with success. Some measures of centrality however, as betweenness, have disadvantages that do not facilitate the research in this area. We show that with the aid of scale-free network characteristics such as the clustering coefficient we can get results that balance the current centrality measures, but also gain insight into the workings of these networks.
Correlation Model of Worm Propagation on Scale-Free Networks
Authors: Nikoloski Zoran , Deo Narsingh , Kucera Ludek
Published: August 2006

The problem of network worms is worsening despite increasing efforts and expenditure on cyber-security. Worm propagation is a random process that creates a complex system of interacting agents (worm copies) over the propagation medium – a scale-free graph, representing real-world networks. Understanding the propagation of network worms on scale-free graphs is the first step towards devising effective techniques for worm quarantining. After presenting the drawbacks of existing mean-field models, we develop a pair-approximation (correlation) model of worm propagation that employs the salient network characteristics – order, size, degree distribution, and transitivity. Inclusion of the transitivity shows significant improvement over existing pair-approximation models. The validity of the model is confirmed by comparing the numeric solution of the model to results from our individual-based simulation. Our model demonstrates that the network structure has considerable impact on the propagation dynamics when the worm uses local propagation strategies.
Spectral karyotyping of human, mouse, rat and ape chromosomes – applications for genetic diagnostics and research
Authors: Schrock E. , Zschieschang P. , O’Brien P. , Helmrich A. , Hardt T. , Matthaei A. , Stout-Weider K.
Published: August 2006

Spectral karyotyping (SKY) is a widely used methodology to identify genetic aberrations. Multicolor fluorescence in situ hybridization using chromosome painting probes in individual colors for all metaphase chromosomes at once is combined with a unique spectral measurement and analysis system to automatically classify normal and aberrant chromosomes. Based on countless studies and investigations in many laboratories worldwide, numerous new chromosome translocations and other aberrations have been identified in clinical and tumor cytogenetics. Thus, gene identification studies have been facilitated resulting in the dissection of tumor development and progression. For example, different translocation partners of the TEL/ETV6 transcription factor that is specially required for hematopoiesis within the bone marrow were identified. Also, the correct classification of complex karyotypes of solid tumors supports the prognostication of cancer patients. Important accomplishments for patients with genetic diseases, leukemias and lymphomas, mesenchymal tumors and solid cancers are summarized and exemplified. Furthermore, studies of disease mechanisms such as centromeric DNA breakage, DNA double strand break repair, telomere shortening and radiation-induced neoplastic transformation have been accompanied by SKY analyses. Besides the hybridization of human chromosomes, mouse karyotyping has also contributed to the comprehensive characterization of mouse models of human disease and for gene therapy studies.
Multicolor fluorescence in situ hybridization (FISH) applied to FISH-banding
Authors: Liehr T. , Starke H. , Heller A. , Kosyakova N. , Mrasek K. , Gross M. , Karst C. , Steinhaeuser U. , Hunstig F. , Fickelscher I. , Kuechler A. , Trifonov V. , Romanenko S.A. , Weise A.
Published: August 2006

During the last decade not only multicolor fluorescence in situ hybridization (FISH) using whole chromosome paints as probes, but also numerous chromosome banding techniques based on FISH have been developed for the human and for the murine genome. This review focuses on such FISH-banding techniques, which were recently defined as ‘any kind of FISH technique, which provide the possibility to characterize simultaneously several chromosomal subregions smaller than a chromosome arm. FISH-banding methods fitting that definition may have quite different characteristics, but share the ability to produce a DNA-specific chromosomal banding’. While the standard chromosome banding techniques like GTG lead to a protein-related black and white banding pattern, FISH-banding techniques are DNA-specific, more colorful and, thus, more informative. For some, even high-resolution FISH-banding techniques the development is complete and they can be used for whole genome hybridizations in one step. Other FISH-banding methods are only available for selected chromosomes and/or are still under development. FISH-banding methods have successfully been applied in research in evolution- and radiation-biology, as well as in studies on the nuclear architecture. Moreover, their suitability for diagnostic purposes has been proven in prenatal, postnatal and tumor cytogenetics, indicating that they are an important tool with the potential to partly replace the conventional banding techniques in the future.
Multicolor banding technique, spectral color banding (SCAN): new development and applications
Authors: Kakazu N. , Abe T.
Published: August 2006

Conventional banding techniques can characterize chromosomal aberrations associated with tumors and congenital diseases with considerable precision. However, chromosomal aberrations that have been overlooked or are difficult to analyze even by skilled cytogeneticists were also often noted. Following the introduction of multicolor karyotyping such as spectral karyotyping (SKY) and multiplex-fluorescence in situ hybridization (M-FISH), it is possible to identify this kind of cryptic or complex aberration comprehensively by a single analysis. To date, multicolor karyotyping techniques have been established as useful tools for cytogenetic analysis. However, since this technique depends on whole chromosome painting probes, it involves limitations in that the origin of aberrant segments can be identified only in units of chromosomes. To overcome these limitations, we have recently developed spectral color banding (SCAN) as a new multicolor banding technique based on the SKY methodology. This new technique may be deemed as an ideal chromosome banding technique since it allows representation of a multicolor banding pattern matching the corresponding G-banding pattern. We applied this technique to the analysis of chromosomal aberrations in tumors that had not been fully characterized by G-banding or SKY and found it capable of (1) detecting intrachromosomal aberrations; (2) identifying the origin of aberrant segments in units of bands; and (3) precisely determining the breakpoints of complex rearrangements. We also demonstrated that SCAN is expected to allow cytogenetic analysis with a constant adequate resolution close to the 400-band level regardless of the degree of chromosome condensation. As compared to the conventional SKY analysis, SCAN has remarkably higher accuracy for a particular chromosome, allowing analysis in units of bands instead of in units of chromosomes and is hence promising as a means of cytogenetic analysis.
Cryptic terminal chromosome rearrangements in colorectal carcinoma cell lines detected by subtelomeric FISH analysis
Authors: Stewénius Y. , Tanke H.J. , Wiegant J. , Gisselsson D.
Published: August 2006

Epithelial tumour karyotypes are often difficult to study by standard cytogenetic methods because of poor chromosome preparation quality and the high complexity of their genomic rearrangements. Subtelomeric fluorescence in situ hybridisation (FISH) has proved to be a useful method for detecting cryptic constitutional chromosomal rearrangements but little is known about its usefulness for tumour cytogenetic analysis. Using a combination of chromosome banding, multicolour karyotyping and subtelomeric FISH, five colorectal cancer cell lines were characterised. The resulting data were compared to results from previous studies by comparative genomic hybridisation and spectral karyotyping or multicolour FISH. Subtelomeric FISH made it possible to resolve several highly complex chromosome rearrangements, many of which had not been detected or were incompletely characterised by the other methods. In particular, previously undetected terminal imbalances were found in the two cell lines not showing microsatellite instability.
Multicolor fluorescence in situ hybridization (M-FISH) on cells from urine for the detection of bladder cancer
Authors: Junker K. , Fritsch T. , Hartmann A. , Schulze W. , Schubert J.
Published: August 2006

Bladder cancer is the fifth most common cancer in adults. Because of the high recurrence rate (up to 70%) new tumor markers for urine are necessary for monitoring patients. In this study, we investigated the value of M-FISH on cells from urine for the detection of bladder cancer. Urine samples from 141 patients suspicious of bladder cancer were analyzed in this study. Cells were isolated from urine before surgical therapy. For FISH analysis, a commercial kit (UroVysion) containing hybridization probes for chromosomes 3, 7, 9p21 and 17, was used. Twenty-five cells were analyzed in each case by two observers. A FISH result was obtained in 121 cases. Overall, sensitivity was 60% and specificity reached 82.6%. Sensitivity and specificity by cytology were 24.1% and 90.5%, respectively. Analyzing results concerning T-category, sensitivity of FISH and cytology was 36.1% and 15% in pTa, 65.2 and 25.7% in pT1, 100% and 66.7% in pT2–3 tumors, respectively. Concerning tumor grade, similar results were obtained: sensitivity was 37% and 14% in G1, 65.4% and 40% in G2, 91.7% and 50% in G3 tumors, for FISH and cytology, respectively. In conclusion, FISH on cells from urine has been shown in all studies to be highly sensitive and specific for detection of bladder cancer. Sensitivity of FISH is higher than conventional cytology and can be used in routine diagnosis additionally to conventional cytology especially in doubtful or negative cases. FISH can detect recurrence earlier than other methods like cytology, cystoscopy or biopsy histological examination.
Cytogenetic characteristics of a murine in vitro model for the human anaplastic large cell lymphoma (ALCL)
Authors: Rudolph C. , Bittner C. , Feller A.C. , Merz H. , Schlegelberger B.
Published: August 2006

Anaplastic large cell lymphoma (ALCL) is an entity of non-Hodgkin lymphomas (NHL) that often occurs in young children and adolescents. In the majority of cases, ALCL are of T-cell origin and contain the t(2;5)(p23;q35) leading to an NPM-ALK fusion or variant ALK translocations. In addition, there is an ALK-negative subtype of ALCL. The anaplastic lymphoid cell line TS1G6 established by interleukin (IL)-9 transfection of T-helper cells represents a murine model of this subtype. Here, we describe the cytogenetic features of this cell line using spectral karyotyping (SKY) and single-color fluorescence in situ hybridization (FISH). We show that TS1G6 cells exhibit a hypotetraploid karyotype with complex structural alterations. Several unbalanced translocations involved the chromosomal region 14E5, and different translocation partners, i.e. X?A6, 3A3 and 8A1. FISH analysis using a BAC clone containing c-myc confirmed the presence of six copies, but also demonstrated that two loci were irregularly located, indicating that additional intrachromosomal rearrangements had occurred. Moreover, a duplication of the region XF2∼3 was identified. Furthermore, six chromosomes 15 were found, representing a trisomy 15 in a tetraploid chromosome complement, indicating an altered gene dosage of the oncogene c-myc located in region 15D3.
De novostructural chromosomal imbalances: molecular cytogenetic characterization of partial trisomies
Authors: Dufke A. , Singer S. , Borell-Kost S. , Stötter M. , Pflumm D.A. , Mau-Holzmann U.A. , Starke H. , Mrasek K. , Enders H.
Published: August 2006

De novo structural chromosomal imbalances represent a major challenge in modern cytogenetic diagnostics. Based solely on conventional cytogenetic techniques it may be impossible to identify the chromosomal origin of additional chromosomal material. In these cases molecular cytogenetic investigations including multicolor-FISH (M-FISH), spectral karyotyping (SKY), multicolor banding (MCB) and cenM-FISH combined with appropriate single-locus FISH probes are highly suitable for the determination of the chromosomal origin and fine characterization of derivative chromosomes. Here we report on four patients with de novo chromosomal imbalances and distinct chromosomal phenotypes, three of them harboring pure partial trisomies: a mildly affected boy with pure partial trisomy 10q22.2→q22.3∼23.1 due to an interstitial duplication, a girl with pure trisomy 12p11.21→pter and atypically moderate phenotype as the consequence of an X;autosome translocation, and a girl with multiple congenital abnormalities and severe developmental delay and a 46,XX,15p+ karyotype hiding a trisomy 17pter→17q11.1. The fourth patient is a girl with minor phenotypic features and mental retardation with an inverted duplication 18q10→p11.31 combined with a terminal deletion of 18p32. The clinical pictures are compared with previously described patients with focus on long term outcome.
A retrospective study of preimplantation embryos diagnosed with monosomy by fluorescence in situ hybridization (FISH)
Authors: Cooper M.L. , Darilek S. , Wun W.S. , Angus S.C. , Mensing D.E. , Pursley A.N. , Dunn R.C. , Grunert G.M. , Cheung S.W.
Published: August 2006

This report is a retrospective study of preimplantation embryos diagnosed with monosomy for chromosomes 13, 15, 16, 18, 21, 22, X and Y on day 3 to determine the rate of true positives, false positives and/or mosaicism and to assess if these embryos are suitable for in vitro fertilization (IVF) transfer. In a one year period, 80 patients went through preimplantation genetic diagnosis for aneuploidy screening (PGD-AS). Monosomy was diagnosed in 51 embryos. Fluorescence in situ hybridization (FISH) was then performed on the blastomeres at day 5–7 with commercially available probes using the same probe set that initially identified monosomy for chromosomes 13, 16, 21 and 22 or chromosomes 15, 18, X and Y. Based on FISH analysis, the monosomy diagnosed during routine PGD-AS analysis was confirmed in 17 of the 51 embryos. A euploid result for the specific chromosomes tested was observed in 16 of the 51 embryos while mosaicism was found in the remaining 18 embryos. This results in an estimated false positive rate of 3.8% for a diagnosis of monosomy. Reanalysis of these embryos demonstrates that the majority of monosomy diagnoses represents true monosomy or mosaicism and should be excluded for transfer in IVF. Furthermore, improved understanding from recent emerging data regarding the fate of oocytes in women with advanced maternal age undergoing IVF to the development of early embryos may provide a valuable insight into the mechanism of chromosome mosaicism.
Time of Erythema Onset after Application of Methyl Nicotinate Ointments as Response Parameter: Influence of Penetration Kinetics and Enhancing Agents
Authors: Remane Y. , Leopold C.S.
Published: August 2006

The time of erythema onset may be used as a response parameter for quantification of the cutaneous erythema response induced by methyl nicotinate. The vehicles light mineral oil (LMO; test) and medium chain triglycerides (MCT; standard) were compared with regard to the pharmacodynamic response. Moreover, the influence of penetration enhancers on the time of erythema onset was investigated under zero order penetration kinetics. The enhancers dimethyl sulfoxide, diethylene glycol monoethyl ether and three different glycerides in different concentrations were added to MCT as a standard vehicle. All preparations were applied to the forearms of volunteers under infinite dose conditions at different thermodynamic drug activity levels (0.2–3.2% of the saturation level) and different drug concentrations (0.051–0.816%), respectively. Different penetration kinetics do not influence data of erythema onset, as these data are comparable to those obtained under finite dose conditions (first order penetration kinetics). With regard to the penetration enhancers, a significantly enhanced penetration of methyl nicotinate could be observed only for diethylene glycol monoethyl ether and dimethyl sulfoxide. However, no significant difference between light mineral oil and MCT could be found with regard to penetration enhancement. The time of erythema onset is an easy and efficient parameter for quantification of the pharmacodynamic response caused by nicotinates.
The Role of Immune Response to Staphylococcus aureus Superantigens and Disease Severity in Relation to the Sensitivity to Tacrolimus in Atopic Dermatitis
Authors: Fukushima Hisayo , Hirano Toshihiko , Shibayama Naoko , Miwa Keishi , Ito Tomonobu , Saito Masukichi , Sumida Haruko , Oyake Shinichi , Tsuboi Ryoji , Oka Kitaro
Published: August 2006

Background:Staphylococcus aureus-producing superantigens (SAgs), such as staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin-1 (TSST-1), are frequently observed in atopic dermatitis (AD). However, little has been done to establish the association of immune responses to SAgs and the therapeutic response to immunosuppressive drugs in AD. Therefore, we investigated the prevalence and role of SAgs in the pathophysiology and immunosuppressive drug sensitivity in AD patients. Methods: We classified 29 patients into two groups on the basis of their clinical AD scores: a low-score group (n = 14) corresponding to mild to moderate patients and a high-score group (n = 15) corresponding to severe patients. We estimated the plasma anti-SEB or TSST-1 IgE of these patients and healthy subjects by ELISA. We also estimated individual drug sensitivity by determining drug concentrations that would give 50% inhibition (IC50) of peripheral-blood mononuclear cell (PBMC) proliferation in vitro. Results: The levels of plasma anti-SEB or TSST-1 IgE in the severe patients were significantly higher than those in the mild to moderate patients (p < 0.05 and p < 0.01, respectively). When stimulated with concanavalin A in vitro, PBMCs in the severe patients exhibited low sensitivity to the suppressive efficacy of tacrolimus (FK506) as compared to the mild to moderate patients (p < 0.01). Furthermore, there was a significant correlation between the IC50s of FK506 and plasma anti-TSST-1 IgE levels (p < 0.01). Conclusions: We showed that PBMCs in severe AD patients exhibited lower sensitivity to FK506, and had higher plasma levels of anti-TSST-1 IgE as compared to the mild AD patients. SAgs appear to be one of the causes of decreased PBMC sensitivity to FK506, and therefore an alternative treatment would be useful based on the individual drug sensitivity data and anti-TSST-1 IgE levels.
Tracking Coronary Calcification and Atherosclerotic Lesions in Patients with Stable Angina Pectoris Undergoing Nifedipine Therapy
Authors: Motro Michael , Kirwan Bridget-Anne , de Brouwer Sophie , Poole-Wilson Philip A. , Shemesh Joseph
Published: August 2006

Aims: The objective of the Coronary Calcification (CC) study was to determine in patients with chronic symptomatic coronary artery disease, if, in addition to standard therapy, nifedipine GITS, relative to placebo, would arrest or slow down the progression of calcium or the development of new atherosclerotic lesions in the coronary arteries. Methods and Results: The CC study was part of the ACTION trial. Multi-slice computerized tomography was used to measure and track the progression of CC. Five hundred and eighteen patients were included in this study. The changes in calcium score from baseline every 24 months, over a period of between 4.5 and 6 years, were similar in the nifedipine and placebotreatment groups (p = 0.8). Compared to placebo, more patients in the nifedipine group (71 vs. 60%) were free of new calcified atherosclerotic lesions during follow-up(p = 0.095). Conclusion: Nifedipine GITS was not effective in slowing down the progression of calcium in advanced atherosclerotic plaques in patients with stable angina pectoris. Although statistically not significant, Nifedipine demonstrated a trend in slowing down the development of new atherosclerotic lesions.
Clinical Outcomes Comparing Eptifibatide and Abciximab in ST Elevation Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Interventions
Authors: Midei Mark G. , Coombs Vicki J. , Lowry David R. , Drossner Michael N. , Prewitt Kerry C. , Wang John C. , Loughrey Michele B. , Gottlieb Sidney O.
Published: August 2006

Background: Randomized clinical trials comparing glycoprotein IIb-IIIa inhibitors have largely excluded patients with ST segment elevation myocardial infarction (STEMI). Methods: We conducted an open-label, sequential comparison of inhospital and 6-month clinical outcomes in STEMI patients receiving eptifibatide or abciximab as adjunctive therapy during percutaneous coronary intervention (PCI). Registry data were collected and compared for STEMI patients undergoing PCI and receiving eptifibatide or abciximab over a 3.5-year period. Six-month follow-up, using telephone interviews, included major adverse cardiac events and functional status. Results: Baseline characteristics were similar for patients receiving eptifibatide (n = 294) or abciximab (n = 158). No significant differences in hospital clinical outcomes were observed for reinfarction (2 vs. 3% for eptifibatide and abciximab, respectively), repeat revascularization (3 vs. 4%), bleeding complications (8 vs. 12%), congestive heart failure (5 vs. 3%), cerebrovascular accidents (0 vs. 2%), renal failure (2 vs. 3%), and all-cause mortality at discharge (5 vs. 4%). No significant difference was seen between groups in all-cause mortality at 6 months (6.5 vs. 6.4%; hazard ratio 0.976; 95% confidence interval 0.43–2.23; log-rank, p = 0.95). Conclusions: No significant differences were observed in clinical outcomes between STEMI patients receiving eptifibatide or abciximab in the setting of PCI. Considering the substantially lower cost of eptifibatide, these data suggest that eptifibatide can be substituted for abciximab to lower overall medication costs while maintaining beneficial safety and efficacy effects.
Anencephaly and Pregnancy Outcome in Iran
Authors: Hatami M. , Khatamee M.A. , Matin M. , Valaei N.
Published: August 2006

Objectives: The aim of this research is to study the complications of pregnancy associated with anencephaly. Study Methods: Thirty-five mothers who delivered an anencephalic baby (as a case group) and forty-three mothers who delivered a non-anencephalic baby (as a control group)were included in this analytical research study. All cases and controls had singleton pregnancies. More than one matched control was chosen for each case when possible. The cases were selected by a survey of 149,000 births in six educational centers located in Tehran. The control group matched with the study group regarding birth date, maternal age, socioeconomic status and living environment. The outcomes for the control and study groups were studied and compared in the following areas: premature rupture of membrane, pregnancy length, fetal presentation, hydramnios, fetal death, sex ratio (male to female ratio) and other anomalies. Results: Anencephaly increased the likelihood of premature rupture of membrane by a factor of seven (p < 0.001). Pre-term birth was six times more likely (p < 0.005) and acephalic fetal presentation was 46% (p < 0.0005). In the study group, sex ratio was 0.52 and in control was 1.68 (p < 0.025). Further, hydramnios appeared in 90% of the study group. Finally, the general likelihood of any abnormality was 19 times (p < 0.0005) greater in the study group than the control group. Conclusions: Considering the clear correlation between anencephaly and pregnancy complications, precise prenatal care, early diagnosis and treatment are strongly indicated in order to avoid serious maternal complications.
Cholesterol Crystal Embolism Syndrome in Dialysis Patients: An Emerging Clinical Diagnosis?
Authors: Piccoli Giorgina Barbara , Fenoglio Roberta , Colla Loredana , Bilucaglia Donatella , Mezza Elisabetta , Burdese Manuel , Bermond Francesca , Segoloni Giuseppe Paolo
Published: August 2006

Background: Cholesterol crystal embolism syndrome (CCE) is an increasing end-stage renal disease cause. Few cases have been described on dialysis, despite the high prevalence of the predisposing factors. Methods: The diagnostic criteria of the present study were: skin lesions, myalgia, fatigue, fever and acute inflammatory serologic signs, in the presence of severe vasculopathy. The precipitating factors were: anticoagulation, endovascular intervention and ulcerated atherosclerotic plaque. Results: Between October 2003 and September 2005, CCE was diagnosed in 6 dialysis patients (of 200–210 on chronic treatment): 5 males, 1 female, median age 59.5 years (47–70) and end-stage renal disease follow-up 11.5 years (3–25). All had severe vasculopathy, 5 cardiopathy, and 4 were failed graft recipients. The treatment included: peritoneal dialysis, daily dialysis, ‘conventional’ hemodialysis (2 cases) and hemodiafiltration. The diagnosis was based on the clinical-laboratory picture in 1 patient. In the 5 others clues were present (dicumarol therapy, angioplasty, femoral artery thrombosis, CCE predialysis and ulcerated aortic plaque). The therapeutic approach consisted of corticosteroids (5 cases), statins (4 cases) and prostaglandin analogues (4 cases). Conclusion: The differential diagnosis of CCE should also be considered in dialysis patients (necrotic lesions, limb pain and vasculitis-like signs).
Impact of Angiotensin II Receptor Blocker on Plasma Levels of Adiponectin and Advanced Oxidation Protein Products in Peritoneal Dialysis Patients
Authors: Furuya Ryuichi , Odamaki Mari , Kumagai Hiromichi , Hishida Akira
Published: August 2006

Background: Oxidative stress and adipocytokines are reported to contribute to the pathogenesis of atherosclerosis. Though the inhibition of the renin-angiotensin system is known to have beneficial effects on atherosclerosis, the exact mechanisms for this remain to be clarified. The aim of this study was to determine the effects of angiotensin II receptor blockers (ARB) on the oxidative stress and adipocytokines in peritoneal dialysis patients. Methods: Candesartan (8 mg/day), an ARB, was administered for 3 months to 8 nondiabetic patients on peritoneal dialysis. Plasma levels of advanced oxidation protein products (AOPP) and adiponectin were measured before and 3 months after candesartan administration, and 3 months after discontinuation. Results: Plasma AOPP level decreased from 377.5 to 305.6 µmol/l (p < 0.05) following the administration of candesartan and returned to 394.6 µmol/l (p < 0.05) by 3 months after the discontinuation of the drug. Plasma adiponectin level increased from 12.5 to 18.8 µg/ml (p < 0.05) by candesartan and decreased again to 14.4 µg/ml (p < 0.05) after discontinuation. There was a significant inverse relationship between changes in plasma level of adiponectin and AOPP (r = – 0.888, p < 0.01). Conclusion: Candesartan increases plasma adiponectin level in association with the reduction of oxidative stress in peritoneal dialysis patients. Candesartan may be useful in preventing atherosclerosis in peritoneal dialysis patients.
Prolonged Parvovirus B19 Viremia in Spite of Neutralizing Antibodies after Erythema Infectiosum in Pregnancy
Authors: Dobec Marinko , Juchler Antoinette , Flaviano Alois , Kaeppeli Franz
Published: August 2006

Objective: To check the clearance of parvovirus B19 in the course of the development of neutralizing antibodies after Erythema infectiosum in pregnancy. Methods: Parvovirus B19 serology (Parvovirus B19 IFA IgG, IgM Antibody Test Kit, Biotrin, Ireland and Immunoblot RIDA Blot Parvovirus B19, R-Biopharm, Germany) and polymerase chain reaction (PCR Parvovirus B19, Roche Diagnostics, Switzerland) were performed in eight predelivery sera, one cord blood sample and one serum 2 months after delivery. Results: Acute parvovirus B19 infection in pregnancy was diagnosed by seroconversion in the IgM and IgG antibody class and detection of viral DNA by PCR. Despite the presence of neutralizing antibodies, PCR gave positive results in all subsequent sera including the cord blood sample and the postdelivery sample 7 months after primary infection. Neonatal examination on the 4th day after delivery was normal and no clinical sign of intrauterine infection was noted. Conclusions: Prolonged parvovirus B19 viremia infection can be seen in spite of neutralizing IgG antibodies and in IgM negative patients. Therefore, the presence of IgG antibodies in the absence of IgM antibodies should not always be interpreted as a past infection. The infectivity of patients with persistent parvovirus B19 infection requires further studies.
Postoperative Transhepatic Arterial Chemoembolization and Portal Vein Chemotherapy for Patients with Hepatocellular Carcinoma: A Randomized Study with 131 Cases
Authors: Li Q. , Wang J. , Sun Y. , Cui Y.L. , Juzi J.T. , Qian B.Y. , Hao X.S.
Published: August 2006

Objective: To explore the value of postoperative transarterial chemoembolization (TACE) and portal vein chemotherapy (PVC) in patients with hepatocellular carcinoma (HCC) in the prevention of recurrence, and to evaluate prognostic factors in a randomized study. Method: 131 patients with HCC were randomly divided into 3 groups: operation only (group A, n = 45); operation plus TACE (group B, n = 39), and operation plus TACE and PVC (group C, n = 47). Disease-free survival rates as well as prognostic factors were analyzed. Results: Most of the side effects and complications related to the operation, catheters and local chemotherapy were liver decompensation (16.1%), catheter obstruction (12.9%), and nausea and loss of appetite (25.8%), respectively. The disease-free survival curves were significantly different between the 3 groups as estimated by the Kaplan-Meier method (p < 0.05). Group C had a significantly higher disease-free survival rate compared to group A (p < 0.05). But no statistical differences were found between groups A and B and groups B and C (both p > 0.05). Tumor number and treatment modalities were independent prognostic factors for HCC patients (p < 0.05). Conclusion: Postoperative TACE combined with PVC may benefit the survival of patients with HCC. In specialized medical centers, aggressive methods such as TACE and PVC should be attempted on HCC patients without contraindications.
Primary Closure of the Skin after Stoma Closure
Authors: Vermulst N. , Vermeulen J. , Hazebroek E.J. , Coene P.P.L.O. , van der Harst E.
Published: August 2006

Background and Aims: Whether or not the skin can be closed primarily after stoma closure is still debated in the existing literature. Therefore, this present study was undertaken to compare the complications and consequences between primary or delayed closure of the skin after stoma closure. Patients and Methods: All consecutive stoma closures between January 2001 and August 2004 were included. In 25 patients (group I), the skin at the stoma site was closed primarily. In 37 patients (group II), the skin was left open. Patient characteristics, comorbidity, medication use, hospital stay and long-term complications were recorded and retrospectively compared between the two groups. Results: In group I, wound infection rate was 36% versus 5% in group II (p = 0.005). Infected wounds were mostly found after ileostomy closure with primary closure of the skin (p = 0.018). The occurrence of a wound infection was not related to the use of corticosteroids, diabetes mellitus, fistula formation, anastomotic leakage, or primary disease and did not lead to a prolonged hospital stay or an increased number of incisional hernias. Conclusion: In our opinion, it is safe to close the skin after stoma closure, but patients should be informed carefully about the advantages and disadvantages of this strategy, especially in case of ileostomy closure.
Proenkephalin-A mRNA Is Widely Expressed in Tissues of the Human Gastrointestinal Tract
Authors: Monstein Hans-Jürg , Grahn Niclas , Ohlsson Bodil
Published: August 2006

Background: It has been shown that the non-opioid effects of Met-enkephalin, which is derived from proenkephalin-A, are mediated through a specific opioid growth factor (OGF) receptor which is assumed to be involved in the control of cell growth. The expression and tissue location of proenkephalin-A mRNA in the gastrointestinal tract remains largely unknown. Methods: In this study we have analyzed the expression of proenkephalin-A mRNA in the human esophagus, gastrointestinal tract and surrounding organs by means of reverse-transcriptase PCR (RT-PCR). Results: The present study demonstrates proenkephalin-A mRNA expression in the human esophagus, gastrointestinal tract, pancreas, and gallbladder. Conclusion: The present study demonstrates proenkephalin-A mRNA expression in regions of the human esophagus, gastrointestinal tract, pancreas, and gallbladder tissues which provides information for the future mapping of proenkephalin-A mRNA and protein expression/co-expression at the cellular level.
Sensitization to Rabbit Allergens in Italy – A Multicentre Study in Atopic Subjects without Occupational Exposure
Authors: Liccardi Gennaro , Passalacqua Giovanni
Published: August 2006

Background: Rabbits as pets are becoming popular in Italy, but few data are available on sensitization to rabbits in patients without occupational exposure. In a multicentre study, we assessed the prevalence of rabbit sensitization in atopic subjects and their modality of exposure. Methods: Allergists from the whole country were required to assess the presence of skin prick test positivity to rabbits in about 100 consecutive patients with allergic rhinitis and/or asthma. In the rabbit-positive patients, clinical history, pet ownership and modality of exposure were assessed. Results: Skin tests were performed on 2,329 outpatients, of whom 1,602 had at least one positivity. Among them, 39 (2.43%) were sensitized to rabbit dander (4 monosensitized). The prevalence of sensitization ranged between 0.65 and 4.72%. Nineteen patients reported direct rabbit contact (10 for ownership and 9 for occasional contact) and 5 patients only indirect exposure through the contact with rabbit owners. Fifteen subjects denied any direct or indirect exposure. All the monosensitized patients were rabbit owners and had persistent (moderate-severe) respiratory symptoms. Conclusions: Sensitization to rabbit in Italy is not to be neglected. In atopic subjects without occupational exposure, contact and indirect exposure to rabbits may induce sensitization. A progressive increase in rabbit sensitization is expected in the future as consequence of the increased rabbit ownership.
Drug Rash with Eosinophilia and Systemic Symptoms versus Stevens-Johnson Syndrome – a Case that Indicates a Stumbling Block in the Current Classification
Authors: Wolf Ronni , Davidovici Batya , Matz Hagit , Mahlab Keren , Orion Edith , Sthoeger Zev M.
Published: August 2006

A 43-year-old man developed a skin eruption characterized by ‘macules with blisters’ typical to Stevens-Johnson syndrome, as well as erosions of the lips and buccal mucosa, 2 weeks after he had started treatment with lamotrigine. He had a fever (39.6°C), elevated liver enzymes and atypical lymphocytes in the peripheral blood. This undoubtedly reflects a case of Stevens-Johnson syndrome induced by lamotrigine, but it can also fulfill the criteria of anticonvulsant hypersensitivity syndrome or drug rash with eosinophilia and systemic signs. A case that precisely fits the definition of two syndromes that have different characteristics, different treatments and different prognoses indicates that there is a flaw in the classification.
Basophil Interleukin 4 and Interleukin 13 Production Is Suppressed during the Early Phase of Rush Immunotherapy
Authors: Plewako Halina , Wosińska Katarzyna , Arvidsson Monica , Björkander Janne , Skov Per Stahl , Håkansson Lena , Rak Sabina
Published: August 2006

Background: Studies using rush immunotherapy (RIT) have shown that rapid protection can be achieved using protocols allowing a fast increment of allergen dose. We examined the early effects of RIT on basophil numbers and expression of CD203c, production of interleukin (IL)-4 and IL-13 and histamine release by basophils in the peripheral blood of patients treated with immunotherapy and controls. Methods: Twelve patients treated with RIT and 4 untreated controls were included in the study. Any adverse events were evaluated during the incremental phase of RIT. Mononuclear cells were isolated before the start of RIT and 3 days, 1 week, 4 weeks and 3 months after the beginning of the treatment. Histamine release upon allergen stimulation, expression of CD203c and allergen-induced production of IL-4 and IL-13 by basophils were examined. Results: Significant decreases in blood basophil count (p = 0.02) were observed early in the treatment, returning to baseline values 1 week after the start of RIT. Similarly, histamine release decreased at day 3 (p = 0.02), but returned to pretreatment levels after 1 week. Also, the percentage of IL-4+ and IL-13+ basophils and levels of CD203c expression were markedly reduced early in the treatment. IL-4 and IL-13 production correlated with histamine release and CD203c expression. Histamine release and production of IL-4 and IL-13 by basophils before the treatment correlated with the severity of adverse events during the incremental phase of RIT. Conclusion: We report the decrease in blood basophil numbers, their lower activation status and the reduced production of IL-4 and IL-13 early in the course of RIT. This early suppression of basophil activation could be one mechanism behind the protective effect of RIT.