Blind and naive classification of toxicity by fish chromatophores

Cellular and molecular pathways involved in the ability of animals to change color have been studied previously as biosensors and cytosensors of active and toxic agents, but such studies generally have been limited to just a few standardized agents. Here we describe the performance of cultured chromatophore pigment cells from the fin tissue of Siamese fighting fish as sensors of toxic agents under blind sampling conditions at the September 2002 EILATox-Oregon Workshop. Detection was accomplished by monitoring motor protein-mediated movements of cellular pigment in chromatophores at both the gross population level as well as in singly imaged cells. Pigment responses were recorded both during the exposure of chromatophores to each blind sample as well as afterwards when the cells were examined for after-effects by challenging them with clonidine, an adrenergic drug that induces standardized pigment movements. After recording all results and upon breaking the key to reveal the identities of the toxic agents, it was found that all of the toxic samples in the study had been distinguished accurately from non-toxic controls that were included among the blind samples. Furthermore, it was revealed that most of the toxic agents detected had never before been tested or calibrated against chromatophores, demonstrating that detection can be achieved under naive conditions that have not been optimized for the analysis of any particular toxic agent. Finally, by organizing the results into categories of pigment responses, a binary classification tree was generated that distinguished each toxic agent as having a distinct response pattern from the others. Thus, chromatophore-based cytosensors can discover toxicity in the absence of prior knowledge of the agent in question, and the categories of responses of the cells can be used to distinguish one toxic agent from another.     

Risk factors for unexplained antepartum fetal death in Norway 1967-1998

OBJECTIVE: To relate unexplained antepartum fetal death with maternal and fetal characteristics in order to identify risk factors. DESIGN: Population-based study based on records of 1,676,160 singleton births with gestational age > or =28 weeks. Unexplained antepartum fetal death was defined as fetal death before labour without known fetal, placental, or maternal pathology. RESULTS: Although unexplained fetal mortality in general declined from 2.4 per 1000 births in 1967-1976 to 1.6 in 1977-1998, the proportion among all fetal deaths increased from 30% to 43% during the same period of observation. Unexplained fetal death occurred later in gestation than explained. From 39 weeks of gestation, the risk increased progressively to 50/10,000 in women aged > or =35 years and <10/10,000 in women <25 years. In birth order > or =5, the risk was particularly high after 39 weeks of gestation. For birth weight percentile 2.5-9.9 and > or =97.5, unexplained fetal death was four and three times more likely to occur, respectively. We found an additive effect of maternal age and birth weight percentile 2.5-9.9. Women with less than 10 years education had higher risk than women with 13 years or more (OR=1.6). Weaker associations were observed with female gender, unmarried mothers, and winter season. CONCLUSIONS: Unexplained antepartum fetal death occurred later in gestation than explained and was associated with high maternal age, multiparity, low education, and moderately low and high birth weight percentile. The increased risk in post-term pregnancies and the additive effect of maternal age and birth weight percentile 2.5-9.9 suggests that older women would benefit from monitoring of fetal growth.     

Unexplained antepartum fetal death in Norway, 1985-97: diagnostic validation and some epidemiologic aspects

OBJECTIVE: To validate the diagnosis of an unexplained antepartum fetal death in the Medical Birth Registry of Norway against data obtained from hospital records, alone and combined with autopsy data. To compare epidemiologic characteristics of an unexplained fetal death based on cases recorded by the three data sources. METHODS: Data on unexplained fetal deaths in the Registry were compared with clinical and autopsy data from 108 457 singletons with a gestational age >or= 28 weeks or a birthweight >or= 1000 g delivered in 1985-97 at Haukeland Hospital in Bergen and Aker Hospital in Oslo. RESULTS: Compared with clinical data, the positive and negative predictive values of a Registry diagnosis of an unexplained fetal death were 88% and 86%, respectively, while the sensitivity and specificity were 76% and 93%, respectively. Compared with clinical and autopsy data combined, the positive and negative predictive values of a Registry diagnosis of an unexplained fetal death were 77% and 89%, respectively, while the sensitivity and specificity were 78% and 88%, respectively. High agreement was observed in comparisons between the data sources of risks according to various independent variables. CONCLUSIONS: The validity of a diagnosis of an unexplained antepartum fetal death based on the Medical Birth Registry of Norway is sufficiently high to justify future large-scale epidemiologic studies based on this database.     

Dedicated composite fillings--inlays

BACKGROUND: The aim of the study was to evaluate the quality and persistence of esthetics of dedicated inlay by clinical methods. METHODS: The paper reviews the clinical significance and technique of preparing particular composite inlays before and after the construction of the metallic framework partial denture. On the basis of indications the total of 30 inlays were placed into cavities under relatively dry working conditions. Six, twelve, eighteen and twenty-four months after the placement of filling, control check-up was carried out by Ryge criteria. RESULTS: After two years marginal discoloration as well as the change of the colour occurred in 3.3% of inlays. There was neither detectable secondary caries, nor the symptoms of pulpal damage. The requirements to be fulfilled concerning the composite materials, in order that they can be implemented for this purpose, were also discussed. CONCLUSION: From the clinical point of view, purpose inlays from Herculite XRV lab C8B in combination with Opti Bond System and composite cement Porcelite Dual Cure showed high functional and esthetic values in the observational period of two years.     

Vinblastin-carboplatin for metastatic cutaneous melanoma as first-line chemotherapy and in dacarbazine failures

Medical Oncology - First-line treatments of metastatic melanoma are usually decarbazine (DTIC) and/or α-interferon based, with response rates in the range of at most 20–30%. In this...     

Technetium-99m-dimercaptosuccinic acid renal scintigraphy in children with urinary tract infections

The aim of this study was to determine the incidence of abnormal dimercaptosuccinic acid-Tc-99m ((99m)Tc-DMSA) renal scintigraphy findings in children with culture proved urinary tract infection (UTI) with or without vesicoureteral reflux (VUR). (99m)Tc-DMSA renal scintigraphy was performed in 343 children with culture documented UTI (247 girls and 96 boys) aged from three months to 14 years (middle age of 4.82 years). The children studied were all those submitted for renal scintiscan to the Institute of Nuclear Medicine, Military Medical Academy, Belgrade during a five-year period (2000-2004). Micturating cystoureterography (MCU) performed in all patients before (99m)Tc-DMSA scan, revealed VUR in 213 children, while in 130 children VUR was not detected by MCU. In 15 of the 213 children the grade of VUR was I, in 88 was II, in 57 was III, in 33 was IV and 20 children had grade V of VUR. Findings of (99m)Tc-DMSA renal scintigraphy were classified as: normal, equivocal and abnormal. Statistical analysis was performed using c(2)test. In all patients abnormal findings were detected in 38% (131/343), normal in 51% (174/343) and equivocal findings in 11% (38/343). In children with UTI and VUR the incidence of abnormal findings was 53% (112/213), of normal 37% (80/213) and of equivocal findings 10% (21/213). In children with UTI without VUR the incidence of abnormal findings was 15% (19/130), of normal findings 72% (94/130), and of equivocal findings 13% (17/130). The incidence of abnormal findings was significantly higher in children with UTI and VUR than in those with UTI without VUR (P<0.001). In children with VUR grades I, II, III, IV and V abnormal findings were 33%, 32%, 60%, 79% and 95% respectively. The incidence of abnormal findings was higher in children with VUR grades IV and V, than in grade I and II (P<0.001). Our results suggest that (99m)Tc-DMSA renal scintigraphy in children can discriminate between grade I-II and IV-V of VUR and also that in children with UTI and VUR abnormal findings in the scintiscan were more than three times higher than in children with UTI alone.     

The cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in vascular homeostatis and pathophysiology

It is widely accepted that vascular mechanisms are involved in the genesis of many neurological disorders. In particular, blood-brain barrier (BBB) dysfunction has been related to the severity of Alzheimer's disease, encephalopathy due to meningitis, multiple sclerosis, HIV-associated encephalopathy, epilepsy, gliomas and metastatic brain tumors. The BBB may constitute an important therapeutic target to protect neurons after CNS diseases. Both in vivo and in vitro, the functional phenotype of vascular endothelium is dynamically responsive to circulating cytokines, growth factors and puslatile blood flow (shear stress). Shear stress can play a critical role in vascular homeostasis and pathophysiology; it is a major regulator of remodeling in developed blood vessels and in blood vessels affected by atherosclerotic lesions. The physiological fluid mechanic stimulus, shear stress, could be considered to be an important 'differentiative' stimulus capable of modulating endothelial phenotype in vivo. Endothelial cells undergo cell cycle arrest after exposure to physiological levels of shear stress. As for mature endothelial cells, in which flow mediated shear stress may play a role in the induction, progression and/or prevention of atherosclerosis by changing their function, stress may play a role in endothelial cell differentiation from hemopoietic stem cells and/or from embryonic stem cells. Stem cells may be used to repair vascular damage, including loss of EC, due to a variety of diseases (e.g. myocardial neovascularization by adult bone marrow derived angioblasts). In the brain, it was proposed that neuron-producing stem cells may be used to treat Alzheimer's disease, paralysis, etc. Surprisingly, very few investigators are exploring the use of endothelial precursors to revert or prevent cerebrovascular disease. This review summarizes the most recent data related to cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in blood-brain barrier homeostasis and pathophysiology.     

Prognostic value of different factors in breast carcinoma

INTRODUCTION: The aggressive biological behavior of invasive and metastatic cancer is considered to be the most insidious and life-threatening aspect for breast cancer patients. It is mostly the result of changes in many molecular characteristics of tumor cells, including alterations in the mechanisms controlling cell growth and proliferation. AIM: The aim of this retrospective study was to identify predictors of aggressive biological behavior and metastatic potential in breast carcinoma among a number of intrinsic biomarkers of tumor cells such as steroid receptors and oncogene and tumor suppressor gene products. METHODS: Routine formalin-fixed, paraffin-embedded tumor samples were used and sections were stained immunohistochemically with the DAKO Strept ABC method to determine the expression of estrogen receptors (ER), progesterone receptors (PgR), HER-2/neu, bcl-2, Ki-67, p53 and nm23 in 192 consecutive breast carcinoma patients. The results of the quantitative immunohistochemical assays were correlated with clinical and histological data such as patient age, overall survival, tumor size, axillary lymph node status, hystological type, tumor grade, Nottingham prognostic index (NPI) and therapeutic regimens. RESULTS: Univariate analysis revealed that survival was significantly longer for patients with small tumors (P = 0.007), lower tumor grade (P = 0.021), negative axillary lymph nodes (P = 0.002), presence of nm23 protein (P = 0.002), and for patients treated with adjuvant hormonal therapy (P = 0.010). In multivariate analysis the independent factors positively affecting survival were absence of axillary lymph node metastases (P = 0.002), nm23 expression (P = 0.009) and hormonal therapy (P = 0.050). Among patients with positive axillary nodes there was a significantly higher survival rate in patients with nm23 expression compared with nm23-negative patients (P < 0.001). CONCLUSION: Identification of a subset of node-positive breast cancer patients with a more favorable prognosis according to nm23 expression might be clinically useful.     

Trichinella spiralis: shaping the immune response

The co-evolution of a wide range of helminth parasites and vertebrates represented a constant pressure on the host's immune system and a selective force for shaping the immune response. Modulation of the immune system by parasites is accomplished partly by dendritic cells. When exposed to helminth parasites or their products, dendritic cells do not become classically mature and are potent inducers of Th2 and regulatory responses. Treating animals with helminths (eggs, larvae, extracts) causes dampening or in some cases prevention of allergic or autoimmune diseases. Trichinella spiralis (T. spiralis) possess a capacity to retune the immune cell repertoire, acting as a moderator of the host response not only to itself but also to third party antigens. In this review, we will focus on the ability of T. spiralis-stimulated dendritic cells to polarize the immune response toward Th2 and regulatory mode in vitro and in vivo and also on the capacity of this parasite to modulate autoimmune disease--such as experimental autoimmune encephalomyelitis.     

Celiac disease prevalence in children and adolescents with type 1 diabetes from Serbia

Background: The association between celiac disease (CD) and type 1 diabetes mellitus (T1DM) is well known. Up to now, CD prevalence in children and adolescents with T1DM in Serbia has not been reported. The aim of the present study was to determine CD prevalence and its clinical manifestations in patients with T1DM. Methods: One hundred and twenty‐one patients (70 girls, 51 boys; mean age, 10.8 years) with T1DM (mean duration of diabetes, 3.4 years) and 125 control group participants (75 girls, 50 boys; mean age, 10.4 years) were tested for CD on tissue transglutaminase antibodies (tTG). In seven serologically positive T1DM patients endoscopic small bowel biopsies were taken and examined on histopathology. In all patients with CD and T1DM age, duration of T1DM, height for age, body mass index, glycosylated hemoglobin and clinical symptoms were noted. Results: Nine patients with T1DM were positive on IgA tTG antibodies. In seven of them small bowel biopsy was performed, and all were proven to have CD on histopathology. The prevalence of biopsy‐proven CD in children and adolescents with T1DM was significantly higher in the study group compared to controls (5.79%. vs 0.8%, P < 0.05). Conclusion: The significantly higher prevalence of CD in children with type 1 diabetes, in accordance with the large volume of data published in the literature, underlines the need for yearly screening of CD in patients with diabetes in order to promptly start a gluten‐free diet when appropriate.