bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE ASYMPTOTIC BEHAVIOR OF HEATING TIMES
Authors: CHANG CHIN-HUEI , CHOW YUN SHYONG , WANG ZHEN
Published: December 2003

An infinite homogeneous d-dimensional medium initially is at zero temperature, u=0. A heat impulse is applied at the origin, raising the temperature there to a value greater than a constant value u0>0. The temperature at the origin then decays, and when it reaches u0, another equal-sized heat impulse is applied at a normalized time τ1=1. Subsequent equal-sized heat impulses are applied at the origin at the normalized times τn, n=2,3,…, when the temperature there has decayed to u0. This sequence of normalized waiting times τn can be defined recursively by [Formula: see text] where d>0. This heat conduction problem was studied by Myshkis (J. Differential Equations Appl.3 (1997), 89–91), and he posed the problem to find an asymptotic expression for the τn as n→∞. The cases for dimensions d=1 and d≥3 have been treated by Chen, Chow, and Hsieh (J. Differential Equations Appl.6 (2000), 309–318). Here, we deal with the two-dimensional case, d=2.
CHAOTIC BEHAVIOR IN CERTAIN SINGULARLY PERTURBED EQUATIONS WITH PIECEWISE CONSTANT DELAYS
Authors: SEIFERT GEORGE
Published: December 2003

Conditions for the existence of chaotic behavior of some solutions of an equation of the form εx′(t)= -x(t)+f(x([t]), λ), where ε and λ are positive constants and [t] denotes the greatest integer in t, are given. If ε→0, it is shown that solutions tend to piecewise constant functions.
BESSEL FUNCTIONS IN A QUANTUM-BILLIARD CONFIGURATION PROBLEM
Authors: ELBERT ÁRPÁD , LORCH LEE , SZEGO PETER
Published: December 2003

In studying various quantum-billiard configurations, R. L. Liboff (J. Math. Phys.35 (1994) 2218), was led to investigate the vanishing of f(ν)=j2ν,1 - jν2, where jμk is the kth positive zero of the Bessel function Jμ(x). Here we show that the even more general function fα(ν)=cαν,k - cν,k+l is increasing and vanishes once (and only once) in 0<ν<∞, provided α≥π/2 and [Formula: see text], k, l=1,2,3,…. As usual, cμn is the nth positive zero of the cylinder function Cμ(x)=Jμ (x) cos θ - Yμ(x) sin θ. Specialized to Liboff's case, f(ν), this yields not only the existence of a zero of f(ν) but also its uniqueness.
ON THE RECOVERY OF A MANIFOLD WITH PRESCRIBED METRIC TENSOR
Authors: MARDARE CRISTINEL
Published: December 2003

A classical theorem in differential geometry asserts that if a C2-metric tensor satisfies the Riemann compatibility conditions, then it is induced by an immersion. We prove that this theorem still holds true for C1-metric tensors satisfying the Riemann compatibility conditions in a distributional sense.
POSITIVITY OF THE INTERTWINING OPERATOR AND HARMONIC ANALYSIS ASSOCIATED WITH THE JACOBI-DUNKL OPERATOR ON ${\mathbb R}$
Authors: CHOUCHANE F. , MILI M. , TRIMÈCHE K.
Published: December 2003

We consider a differential-difference operator Λα,β, [Formula: see text], [Formula: see text] on [Formula: see text]. The eigenfunction of this operator equal to 1 at zero is called the Jacobi–Dunkl kernel. We give a Laplace integral representation for this function and we prove that for [Formula: see text], [Formula: see text], the kernel of this integral representation is positive. This result permits us to prove that the Jacobi–Dunkl intertwining operator and its dual are positive. Next we study the harmonic analysis associated with the operator Λα,β (Jacobi–Dunkl transform, Jacobi–Dunkl translation operators, Jacobi–Dunkl convolution product, Paley–Wiener and Plancherel theorems…).
Evidence for a Novel Gonadotropin-Releasing Hormone in Hypothalamic and Forebrain Areas in Songbirds
Authors: Bentley George E. , Moore Ignacio T. , Sower Stacia A. , Wingfield John C.
Published: December 2003

One or more of three distinct forms of gonadotropin-releasing hormones (GnRHs), has been found in all vertebrates studied. Birds are known to contain two types of GnRH, chicken GnRH-I and -II (cGnRH-I and -II), but to date nobody has investigated the possibility of the presence of lamprey GnRH-III in birds. Thus, our objective was to investigate the presence and distribution of immunoreactive lamprey (ir-lamprey) GnRH-III in hypothalamic and forebrain areas in house sparrows (Passer domesticus) and Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelii). In addition to its distribution in the CNS, we investigated whether or not exogenous lamprey GnRH-III peptide could elicit luteinizing hormone (LH) release in vivo. This study presents two novel findings: 1) The widespread presence in the central nervous system of an immunoreactive third GnRH in birds that is clearly hypophysiotropic and has gonadotropin-releasing capabilities. Intravenous injection of 100 ng lamprey-GnRH-III peptide elicited a rapid rise in circulating luteinizing hormone as compared to controls. This third GnRH, ir-lamprey GnRH-III, likely has multiple functions, as suggested by its widespread distribution. 2) Ir-lamprey GnRH-III is present in abundance in telencephalic areas, including the hippocampal formation and the song control system. In no vertebrate has a GnRH been localized in these ‘higher’ control regions before. The fact that ir-lamprey-GnRH-III is present in auditory processing areas (higher vocal center, or HVc, area X, caudomedial neostriatum) and song-producing areas (HVc, robust nucleus of the neostriatum, or RA) suggests a direct way in which auditory processing and song production can affect circulating gonadotropins.
The Effects of Egg-Derived Antibodies to Glucosyltransferases on Dental Caries in Rats
Authors: Krüger C. , Pearson S.K. , Kodama Y. , Vacca Smith A. , Bowen W.H. , Hammarström L.
Published: December 2003

The role of Streptococcus mutans in the development of dental caries is well recognized. Important virulence factors include the glucosyltransferases (gtf), essential for production of glucans. We evaluated the anticariogenic effects of orally administered chicken anti-cell-associated (CA) Gtf antibodies in desalivated rats. The animals were infected with S. mutans MT8148R and treated with chicken anti-CA-Gtf egg yolk antibodies (IgY) or nonimmune egg yolk powder. Smooth surface lesions were significantly lower in the anti-CA-Gtf-treated group in comparison to the control groups. Sulcal surface caries was also decreased and of less severity. Our study suggests that chicken anti-CA-Gtf antibodies may have promise as a prophylaxis for high caries risk patients.
Is Attention-Deficit Hyperactivity Disorder a Risk Factor for Dental Caries?
Authors: Broadbent J.M. , Ayers K.M.S. , Thomson W.M.
Published: December 2003

Experience in practice has suggested that children with attention-deficit hyperactivity disorder (ADHD) tend to have higher numbers of diseased, missing and filled teeth (DMFT score) than children without the condition. To date, however, this impression has not been systematically investigated. A case-control study of children in Otago, New Zealand (case DMFT ≧ 5; control DMFT <5; case status determined from School Dental Service dental records) was conducted by postal survey and reference to the School Dental Service records. Cases and controls were matched on age, sex, ethnicity, and school socio-economic status. The purpose of the study was to assess whether having ADHD was associated with higher odds of having high caries experience. Questionnaires were returned for a total of 128 case-control pairs. Conditional logistical regression analysis showed that, after controlling for fluoride history, medical problems, diet, and self-reported oral hygiene, children with ADHD had nearly 12 times the odds of having a high DMFT score than children who did not have ADHD (OR = 11.98; 95% CI 1.13, 91.81). No other factors were significant predictors. Dental practitioners and parents should consider ADHD to be a condition that may affect children’s dental caries experience.
Brushing Abrasion of Softened and Remineralised Dentin: An in situ Study
Authors: Attin T. , Siegel S. , Buchalla W. , Lennon Á.M. , Hannig C. , Becker K.
Published: December 2003

The aim of the present in situ study was to evaluate the effect of different periods of intra-oral remineralisation on the susceptibility of softened dentin to toothbrushing abrasion. Groups of 6 human dentin specimens (A–F) were recessed in the buccal aspects of intra-oral appliances which were worn for 21 days by 11 volunteers. The samples were demineralised twice a day extra-orally in the acidic beverage Sprite Light (pH 2.9) for 90 s. Subsequently, the dentin specimens were brushed at different times. Specimen A was brushed immediately after demineralisation. Specimens B–E were brushed after the intra-oral appliances had been worn for various periods in the mouth: specimen B for 10 min, C for 20 min, D for 30 min and E for 60 min. Specimen F was not brushed (control). After 21 days, dentin wear was measured with a profilometer. The following values (means ± standard deviation) were recorded (µm): A, 23.6 ± 16.7; B, 37.9 ± 29.7; C, 31.8 ± 26.5; D, 18.5 ± 10.5; E, 15.3 ± 11.6; F, 12.6 ± 6.7. There was a statistically significantly increased dentin loss for groups A, B and C as compared to the controls (U test: p < 0.05). However, after intra-oral periods of 30 and 60 min, wear was not significantly higher than in unbrushed controls. It is concluded that for protection of dentin surfaces at least 30 min should elapse before toothbrushing after an erosive attack.
Subinguinal Microsurgical Varicocelectomy: Evaluation of the Results
Authors: Kumar Rajeev , Gupta Narmada P.
Published: December 2003

Introduction: Varicoceles have been established to be the commonest correctable cause of male infertility. Among the various methods available, microsurgical varicocelectomy has one of the lowest complication rates with low failure. Patients and Methods: Over a 4-year period, 100 patients underwent microsurgical varicocelectomy at our center. One hundred and forty-four surgeries were performed on 90 of these patients through a subinguinal approach and these form the study group. Only clinically diagnosed varicoceles were operated. Pre-operative semen values were compared with the post-operative values and statistical analysis performed using a non-parametric test. All 90 patients provided at least 1 post-operative semen report 3 months after surgery while 50 are on complete follow-up. Results: Sperm count improved in 71% patients, normal motility in 60% and normal morphology in 49%. Seventeen of the 50 patients on full follow-up (34%) achieved pregnancy, with 16 of these being spontaneous. All patients achieving pregnancy showed improvement in sperm count, 13 improved in motility and 12 in morphology. All improvements were statistically significant. There were 21 (14.6%) minor complications with no testicular atrophy and 1 recurrence. Conclusion: Microsurgical varicocelectomy is a safe and effective option for the managment of varicocele-induced male infertility. It leads to improvement in all semen parameters and increases the possibility of spontaneous pregnancies.
High-Throughput Tissue Microarray Analysis of erbB-2 Gene Amplification in Urinary Bladder Cancer
Authors: Toncheva Draga I. , Zaharieva Boriana M.
Published: December 2003

Introduction: Overexpression of the receptor Her-2 leads to increased proliferative response to epidermal growth factors which plays a key role in tumor development and growth. Increased oncoprotein level, in the majority of cases, is caused by erbB-2 gene amplification. To define the frequency of amplifications of erbB-2 in bladder cancer, and to determine their association with the tumor phenotype we utilized tissue microarray (TMA) approach. Materials and Methods: We analyzed a TMA consisting of 159 transitional cell bladder carcinomas for erbB-2 gene amplification by dual-color FISH. Results: The frequency of erbB-2 amplification was 5.3% of all successfully analyzed samples (4 of 75). It increased from minimally invasive (pT1) to muscle-invasive (pT2–4) tumors, as well as with advanced tumor grade (G1 to G2 to G3). All amplifications were cluster amplifications confirming the fact that erbB-2 amplification occurs intrachromosomally in bladder cancer. Conclusions: We concluded that despite its low incidence, erbB-2 amplification is of importance for the bladder tumor invasion and progression.
Remission of Idiopathic Retroperitoneal Fibrosis after Sequential Therapy with Corticosteroids and Tamoxifen
Authors: Tan M. Özgür , Uygur M. Cemil , Diker Yusuf , Erol Demokan
Published: December 2003

The most favored therapy for idiopathic retroperitoneal fibrosis is the surgical relief of ureteral obstruction and use of corticosteroids to prevent recurrence. Although effective, long-term corticosteroid treatment could be associated with serious side effects. We would like to present a case of idiopathic retroperitoneal fibrosis treated successfully with intraperitonealization of the ureters and sequential therapy with steroids and tamoxifen to minimize the side effects.
Bacteria Ingestion by Blowfly Larvae: An in vitro Study
Authors: Lerch Klaus , Linde Hans-Jörg , Lehn Norbert , Grifka Joachim
Published: December 2003

Background: Maggot debridement therapy is the medical use of live fly larvae for cleaning chronic and infected wounds, removing devitalized tissue and decreasing the risk of infection. Maggot-derived proteins are able to kill bacteria, and proteolytic enzymes are responsible for the liquefying of necrotic tissue. Objective: The aim of this study is to investigate bacterial ingestion by larvae roaming free on bacterial agar, compared to those larvae contained within vinyl bags. Methods: Free-roaming sterile larvae of Lucilia sericata and larvae contained in vinyl bags were fed on Escherichia coli producing green fluorescent protein (GFP). The time interval to the onset of fluorescent maggots was determined. At different time intervals, maggots were sacrificed, washed in sterile saline, sagittally cut in frozen sections and examined under a microscope with UV light. Results: After feeding on GFP-labelled E. coli, maggots roaming free on bacterial lawn agar demonstrated fluorescence after 3 min, maggots entrapped in vinyl bags after 25 min. In the sagittal frozen sections, the highest fluorescent intensity was detected in the larvae’s rostral part of the alimentary tract, the crop and the anterior midgut. Conclusion: In an in vitro setting, digestion and ingestion of whole or disintegrated bacteria is accomplished within minutes. The vinyl bag’s permeable membrane clearly causes a delay of this process.
Topical Tacrolimus as a Therapeutic Adjunct in Patients with Cutaneous Lupus erythematosus
Authors: Böhm Markus , Gaubitz Markus , Luger Thomas A. , Metze Dieter , Bonsmann Gisela
Published: December 2003

The topical therapy of cutaneous lupus erythematosus (LE) consists mainly of corticosteroids which may lead to significant side effects when overused. We report the efficacy of topical tacrolimus as a therapeutic adjunct in 3 patients with cutaneous LE of the face. All patients, 1 with systemic LE and a malar rash, 1 with annular subacute cutaneous LE, the other with a papular variant of subacute cutaneous LE, experienced significant improvement following application of tacrolimus ointment. Treatment with topical tacrolimus was tolerated well without major side effects in all patients. The presented cases are in line with recent reports that topical tacrolimus may be effective in facial LE.
Deafness Genes and Their Diagnostic Applications
Authors: Cryns Kim , van Camp Guy
Published: December 2003

Hearing impairment (HI) is clinically and genetically very heterogeneous, and auditory genes are discovered at a very rapid pace. The identification of deafness genes is enabling us to understand the molecular process of hearing, and it offers prospects for DNA testing of HI. However, the routine application of these tests is hampered by the large number of genes involved in HI and by the fact that molecular screening of these genes is often quite expensive and time consuming. An important gene that should be considered in congenital or childhood onset autosomal recessive HI is GJB2 since mutations in this gene account for at least 50% of this type of HI. In the present review, we describe the known deafness genes and we provide an overview of the current, routinely used diagnostic DNA tests.
A Novel Connexin 26 Mutation Associated with Autosomal Recessive Sensorineural Deafness
Authors: Frei Klemens , Lucas Trevor , Ramsebner Reinhard , Schöfer Christian , Baumgartner Wolf-Dieter , Weipoltshammer Klara , Erginel-Unaltuna Nihan , Wachtler Franz J. , Kirschhofer Karin
Published: December 2003

Mutations in the connexin 26 (Cx26) gene (GJB2) are a common cause of hereditary hearing impairment which affects approximately 1 in 2000 newborn children. We report the identification of a novel Cx26 point mutation (439 G→A) linked to familial, autosomal recessive, sensorineural hearing loss. This missense mutation (E147K) is located in the highly conserved, putative K+ channel lining sequence of the third transmembrane domain (TM3) of Cx26. Hearing impairment associated with this mutation was congenital, moderate to profound and showed no signs of progressive deterioration.
Progenitor Cells from Human Embryonic Retina – Proliferation and Preferential Differentiation into Ganglion Cells
Authors: Andressen Christian , Briese Volker , Ulfig Norbert
Published: December 2003

Progenitor cells of the retina give rise to 6 principle types of neurons and the Müller glia cells. In the human retina, differentiation starts at around the beginning of the third month of gestation with the appearance of first postmitotic ganglion cells. As histogenesis proceeds, the remaining types of neurones and the Müller glial cells are generated. The precise mechanisms by which multipotent retinal progenitor cells are guided to give rise to the different postmitotic cell types are largely unknown. Here, we describe the isolation and propagation of retinal progenitor cells from human embryos being 7–8 weeks old, during which time the retina is composed of a population of neural-cell-adhesion-molecule-positive neuroepithelial cells. In vitro, the cells responded to the mitogens EGF and FGF-2 and formed neurospheres, indicating their mitotic activity. Withdrawal of the mitogens in combination with plating on laminin-1-coated culture dishes resulted in high numbers of L1-immunoreactive cells with long processes, which are presumably ganglion cells. These observations indicate that the early differentiation of human retinal progenitor cells into ganglion cells in vivo can be reproduced in vitro. Thus, the cell culture developed in the present study is a useful tool to evaluate instructive stimuli involved in the development of additional retinal cell types from the retinal progenitor cells. Knowledge about such stimuli is a prerequisite for a cell replacement therapy in retinopathological diseases.
Results of an Autologous Noncryopreserved, Unmanipulated Peripheral Blood Hematopoietic Stem Cell Transplant Program: A Single-Institution, 10-Year Experience
Authors: Ruiz-Argüelles Guillermo J. , Gómez-Rangel David , Ruiz-Delgado Guillermo J. , Ruiz-Argüelles Alejandro , Pérez-Romano Beatriz , Rivadeneyra Liliana
Published: December 2003

Background: Methods to simplify the stem cell transplantation procedures are needed mainly in developing countries. We have previously shown that unprocessed leukapheresis material is useful to restore hematopoiesis after high-dose chemotherapy. Methods: Over a 10-year period in a private practice setting, we prospectively performed autotransplants using noncryopreserved and unmanipulated peripheral blood stem cells mobilized from the bone marrow to the peripheral blood by means of filgrastim and using a single-day conditioning regimen with high dose (200 mg/m2) melphalan. Results: Forty-six individuals were given 50 autografts. The median age of the patients was 33 years (range 8–69). Twenty-two patients with acute leukemia (13 with myeloblastic and 9 with lymphoblastic leukemia), 4 with chronic myelogenous leukemia, 6 with multiple myeloma, 7 with Hodgkin’s disease, 3 with non-Hodgkin’s lymphoma and 4 with metastatic breast carcinoma were included. The median time to achieve >0.5 × 109/l granulocytes was 14 days (range 0–86), whereas the median time to achieve >20 × 109/l platelets was 25 days (range 0–102). The 3,300-day posttransplant survival was 63%, the median posttransplant overall survival was over 3,300 days, the 3,300-day disease-free survival was 50% and the transplant-related mortality was 2%. The procedure was performed entirely on an outpatient basis in the case of 48 autografts (96%). The approximate cost of each graft was 7,500 USD. Conclusion: This simplified method to autograft patients, avoiding in-hospital stays, purging procedures and cryopreservation of the cells, is feasible and results in a substantial decrease in the cost of the autologous hematopoietic stem cell transplantation methods.
Complete Chorioamniotic Membrane Separation
Authors: Lewi Liesbeth , Hanssens Myriam , Spitz Bernard , Deprest Jan
Published: December 2003

We present a patient who developed complete chorioamniotic membrane separation (CMS) in two consecutive pregnancies. The first pregnancy ended with an intrauterine fetal death at 25 weeks of gestation. The entire separated amniotic sac had twisted around the umbilical cord. In the subsequent pregnancy, a complete CMS was diagnosed at 34 weeks of gestation. In both pregnancies, the patient underwent an early 2nd-trimester genetic amniocentesis. A review of the literature shows that extensive CMS is associated with miscarriage, in utero fetal death, umbilical cord complications, and preterm delivery. Most reported cases occurred after invasive intrauterine procedures.
HIV/AIDS in Central Africa: Pathogenesis, Immunological and Medical Issues
Authors: Sibanda Elopy Nimele , Stanczuk Grazyna , Kasolo Francis
Published: December 2003

The estimated worldwide prevalence of human immunodeficiency virus (HIV) infections topped 52.5 million in June 2003, a mere 20 years after the aetiological agent was shown to be a sexually transmissible virus with a predilection for CD4+ T lymphocytes. More than 22 million people have died of the acquired immunodeficiency syndrome (AIDS) and the condition has in one generation become the most devastating and persistent epidemics in recorded history. More than two thirds of the world total of HIV-infected people live in Sub-Saharan Africa. In Central and Southern Africa at least 20% of the adult population is infected. As these adults die, they leave increasing numbers of orphans. Life expectancy at birth declined by 10 years per decade since the late 1980s to 50 years in the late 1990s, and in Botswana it is estimated to be as low as 33 years by 2010. The epidemic is increasing unabated and prospects for a curative or protective vaccine remain remote. The impact on HIV in Africa has been so profound that it influences political, economic, agriculture/food security, social, education, defence, science and health considerations. The medical and in particular immunology communities in Central Africa have the invidious challenge of on the one hand diagnosing the condition, monitoring its impact and contributing to treatment and management efforts. The science and clinical practice of immunology is challenged to find answers to the epidemic, perhaps including a vaccine. In this review we address the peculiarities of the HIV epidemic in Africa, its epidemiology and immunopathogenesis. We address the effect of the epidemic on individual patients, in their homes, workplaces and the knock-on effects on families and friends of the infected. Respective specialists discuss special groups (women, children) that are predominantly seen in Africa. We also discuss the impact of the epidemic on the clinical practice of medicine in general and challenges faced in the introduction of antiretroviral medicines. We also discuss options available for the diagnosis, treatment and monitoring of HIV-infected patients in this region.
Induction of XY sex reversal by estrogen involves altered gene expression in a teleost, tilapia
Authors: Kobayashi T. , Kajiura-Kobayashi H. , Nagahama Y.
Published: December 2003

To clarify the importance of endogenous estrogens during sex differentiation in a teleost fish, the Nile tilapia, we examined the target events for endogenous estrogens and their role during gonadal sex differentiation. The expression of CYP19a (P450arom) precedes any morphological gonadal sex differentiation. Further to these findings, the treatment of XX fry with non-steroidal aromatase inhibitor (AI), Fadrozole, from seven to 14 days after hatching caused complete sex reversal to functional males. The XX sex reversal induced by AI was rescued completely with simultaneous estrogen treatment. We also found that XY fry treated with estrogen, before the appearance of morphological sex differences, caused complete sex reversal from males to females. Taken together, these results suggest that endogenous estrogens are required for ovarian differentiation. To identify the down-stream gene products of estrogen during ovarian differentiation, we performed subtractive hybridization using mRNA derived from normal and estrogen treated XY gonads. Two out of ten gene products were expressed in germ cells, whereas the others were expressed in somatic cells.
Expression of Dmrt1 in a turtle with temperature-dependent sex determination
Authors: Murdock C. , Wibbels T.
Published: December 2003

There is a variety of sex determining mechanisms among vertebrates. Many reptiles possess temperature-dependent sex determination (TSD), in which the incubation temperature of the egg determines the sex of the hatchling. The red-eared slider turtle, Trachemys scripta has often been used as a model system for examining the physiology of TSD. In the current study, the expression of Dmrt1 was examined during TSD in this turtle. Dmrt1 is a putative regulator of sex determination/differentiation and has been identified in a variety of vertebrates, including fishes, amphibians, reptiles, birds, and mammals. Specifically, Dmrt1 has been shown to be up-regulated in a male-specific pattern during embryonic development in many vertebrates. In the current study, the expression patterns of Dmrt1 were examined in the developing adrenal-kidney-gonad complexes of T. scripta during embryonic development. Using a quantitative competitive RT-PCR, Dmrt1 was shown to be up-regulated during the thermosensitive period of sex determination in males. In contrast, levels of Dmrt1 remained low in females throughout the thermosensitive period. These data suggest that the up-regulation of Dmrt1 may play a role in male sex determination/sex differentiation during TSD in T. scripta.
Experts’ Opinions on the Role of Diet in Caries Prevention
Authors: van Loveren C. , Duggal M.S.
Published: December 2003

A questionnaire was sent to 54 experts in preventive dentistry in 23 European countries in order to make an inventory of existing national dietary guidelines for the prevention of dental caries. In addition, the experts were asked to give their personal opinion on several issues concerning the relationship between diet and dental caries. Forty-five experts from 20 countries returned the questionnaire. In 13 European countries dietary guidelines for caries prevention were available issued by a National (Dental) Association or a Government Body. All guidelines emphasised a reduction of the frequency of intakes of cariogenic foods. Two of them included a threshold level for the amount of sugar. When asked for their personal opinions, almost all experts mentioned reduction of frequency of ‘cariogenic’ intakes as the principal dietary messages for caries prevention. Four experts, however, explicitly mentioned that proper oral hygiene with fluoride toothpaste is more important. There was no agreement among the experts about a daily number of cariogenic intakes in between meals that can be regarded as safe, nor whether the message: ‘Use products with sugar substitutes’ should be part of the dietary guidelines for the prevention of dental caries. There was no agreement amongst experts on preventive dentistry in Europe on the contemporary validity of the paradigm: ‘Sucrose is the arch criminal of dental caries.’ Taking the variation in opinions into account and the fact that a balanced diet may lead to a moderate eating and snacking frequency, the authors propose that the emphasis on good versus bad foods for caries prevention should be replaced by an emphasis on good versus bad diets.
The Role of Diet in the Aetiology of Dental Erosion
Authors: Lussi A. , Jaeggi T. , Zero D.
Published: December 2003

Acids of intrinsic and extrinsic origin are thought to be the main etiologic factors for dental erosion. There is evidence that acidic foodstuffs and beverages play a role in the development of erosion. However, the pH of a dietary substance alone is not predictive of its potential to cause erosion as other factors modify the erosive process. These factors are chemical (pKa values, adhesion and chelating properties, calcium, phosphate and fluoride content), behavioural (eating and drinking habits, life style, excessive consumption of acids) and biological (flow rate, buffering capacity, composition of saliva, pellicle formation, tooth composition, dental and soft tissue anatomy). The interplay between erosion and abrasion (specially oral hygiene practices) may be the main driver leading to the clinical manifestation of this disorder. Recommendations for patients at risk for dental erosion such as reducing acid exposure by reducing the frequency and contact of acids will be discussed.
Intraindividual Variability and Short-Term Change
Authors: Nesselroade John R.
Published: December 2003

Background: Interest in the study of intraindividual variability is growing rapidly. Objective: The present collection of papers deals with both longer-term, growth and change and shorter-term intraindividual variability. Methods: The papers emphasize primarily the former within the context of analyzing large, longitudinal data sets. Also discussed are some key methodological matters. Results: Criteria to help with choosing methods and modeling with missing data are included. Conclusions: A promising direction is toward developing a more systematic and intensive conception of the meaning and significance of the wide variety of manifestations of intraindividual variability and integrating them into theories of aging.
Predictors of Change during Long-Term Analytic Group Psychotherapy
Authors: Lorentzen Steinar , Høglend Per
Published: December 2003

Background: All studies on patient variables as predictors of outcome are on short-term groups. Therefore, we wanted to study predictors of outcome in an observational study of 69 out-patients treated in long-term, analytic group therapy (mean = 32.5 months). Methods: Based on results from research on short-term groups, we selected 6 predictor variables representing central domains (demographics, diagnosis, initial severity of disturbance, chronicity, expectancy, and treatment duration) and explored their relationship with 5 outcome variables (Global Assessment of Functioning, Global Severity Index, Inventory of Interpersonal Problems-Circumplex, global improvement, and chief complaints) by multiple regression analyses. Results: Treatment duration up to 2.5 years was a strong positive predictor. Contrary to findings from many short-term studies, the presence of personality disorder, chronicity, and high initial severity of symptoms were not associated with less favourable outcome. Furthermore, marital status was not a positive predictor, and expectancy of a better outcome was only positively related to 1 of the outcome variables. Highly tentative results from exploratory stepwise regression analyses indicated that interpersonal problems on the subscale of ‘coldness’ might also be a negative predictor in long-term therapy. Conclusions: The study indicates that predictors of outcome in long-term group therapy may be different from those found in short-term therapy.
Excretion of 6-Hydroxymelatonin Sulfate (6-OHMS) in Siblings during Childhood and Adolescence
Authors: Griefahn Barbara , Bröde Peter , Remer Thomas , Blaszkewicz Meinolf
Published: December 2003

The analysis was performed to support the assumption that in inter-individual variations melatonin production is determined genetically. Sixty-six siblings from 31 families (27 girls, 39 boys, 3–18 years) contributed to this study with 3 to 15 urine samples collected once a year over 24 h. The samples were stored at –20°C and analyzed for the daily output of the melatonin metabolite 6-hydroxymelatonin sulfate (6-OHMS) by an enzyme-linked immunosorbent assay (ELISA). The results indicate that 6-OHMS excretion was significantly correlated in siblings (r = 0.37, p = 0.01), suggesting a possible genetic background of melatonin production. However, prospective studies controlling also lifestyle factors such as diet are required to further confirm the hypothesis.
Elderly Patients with Advanced Non-Small Cell Lung Cancer
Authors: Berardi R. , Porfiri E. , Scartozzi M. , Lippe P. , Silva R.R. , Nacciarriti D. , Menichetti E.T. , Tummarello D. , Carle F. , Piga A. , Cellerino R.
Published: December 2003

Objectives: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC. Methods: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 on days 1, 8 and 15 every 28 days. Results: Forty-eight patients with a median age of 74 years (range 70–78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III–IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III–IV thrombocytopenia and 7/48 patients (14.6%) had grade III–IV anemia. One patient experienced grade III emesis and 2 patients had grade III–IV fatigue. Conclusions: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC.
Phase II Study of Gemcitabine plus Docetaxel in Advanced Pancreatic Cancer: A Hoosier Oncology Group Study
Authors: Schneider Bryan P. , Ganjoo Kristen N. , Seitz David E. , Picus Joel , Fata Farid , Stoner Cindy , Calley Cynthia , Loehrer Patrick J.
Published: December 2003

Objective: To determine the response rate, duration of response and survival with weekly gemcitabine plus docetaxel in metastatic or unresectable pancreatic cancer. Methods: Forty patients were enrolled, and 38 patients were evaluable for survival and toxicity. Thirty-seven patients were evaluable for response. Nine patients (24%) had locally advanced disease and 29 (76%) had metastatic disease at the time of enrollment. Median Eastern Cooperative Oncology Group performance status was 1. Patients received gemcitabine 750 mg/m2 i.v. and docetaxel 35 mg/m2 i.v. weekly for 3 out of 4 weeks for a maximum of 6 cycles. Results: Patients received a median of 4 cycles (range 1–6) of chemotherapy. An objective response was obtained in 10 patients (27%) with a median duration of 17 weeks. Median survival was 7 months, and 1-year survival was 19.3%. Eight patients experienced at least one form of grade 4 toxicity and 27 patients experienced at least one type of grade 3 toxicity. Conclusions: The combination of gemcitabine and docetaxel is a well-tolerated regimen with clinical efficacy. The ultimate role of this combination versus single-agent gemcitabine can only be determined by a randomized phase III trial.
Helicobactor pylori Infection Is Closely Associated with Telomere Reduction in Gastric Mucosa
Authors: Kuniyasu Hiroki , Kitadai Yasuhiko , Mieno Hiroshi , Yasui Wataru
Published: December 2003

Objective: To investigate differential reduction in telomere DNA in tissue components of gastric mucosa with respect to Helicobactor pylori infection. Materials and Methods: The telomere content was examined by fluorescent in situ hybridization with the (TTAGGG)4 probe. To compare the signal intensities from the probe (telomere volume) with telomere length, five gastric carcinoma cell lines were used. Telomere volumes were examined in 9 healthy persons, 124 non-cancer patients, and 86 gastric cancer patients. Results: Telomere volume showed a linear correlation with telomere length measured by Southern blotting in gastric carcinoma cells. In healthy persons without H. pylori infection, the telomere volumes of gastric epithelial tissues were 70–79% that of intramucosal lymphocytes (internal control). In 124 patients without gastric cancer, telomere volume of H.-pylori-infected mucosa was significantly less than that of H.-pylori-negative mucosa in both metaplastic and non- metaplastic tissues (p < 0.0001). In 86 gastric cancer patients, telomere volumes in intestinal metaplasia adjacent to cancer were 75% that of intestinal metaplasia of non-cancer patients (p = 0.0001). hTERT expression was detected in 6 cancer-associated and 2 cancer-negative intestinal metaplasia specimens, in which telomere volume was markedly reduced. Conclusion:H. pylori infection is closely associated with telomere reduction in gastric epithelium.
Bcl-2 Family Members as Sentinels of Cellular Integrity and Role of Mitochondrial Intermembrane Space Proteins in Apoptotic Cell Death
Authors: Festjens Nele , van Gurp Marjan , van Loo Geert , Saelens Xavier , Vandenabeele Peter
Published: December 2003

In addition to their function as major energy-providing organelles of the cell, mitochondria accomplish a crucial role in apoptosis. The pro-apoptotic BH3-only members of the Bcl-2 family continuously sense the cellular integrity and well-being at various subcellular levels. If these sentinels are induced, released or activated, they converge on the release of mitochondrial intermembrane space proteins such as cytochrome c, the oxidoreductase AIF, endonuclease G, Smac/DIABLO and the serine protease Omi/HtrA2. We discuss how Bcl-2 family members integrate diverse survival and death signals and act as central regulators of apoptosis. Furthermore, we describe the current knowledge on the role of mitochondrial proteins in apoptotic cell death, discuss the molecular mechanisms of their release and the apoptotic role of mitochondria from a phylogenetic and immunological point of view.
Granzyme B-Induced Cell Death
Authors: Andrade Felipe , Casciola-Rosen Livia A. , Rosen Antony
Published: December 2003

Granzyme B (GrB) is a serine protease that is released by cytotoxic lymphocytes to kill virus-infected and tumor cells. Recent advances in the understanding of GrB have stressed the importance of reassessing the mechanisms by which GrB accomplishes its death functions. These include the uptake and trafficking of GrB within target cells, pathways used to trigger cell death, and the mechanism(s) controlling its killing activity. In addition, the role that GrB plays in human pathologies is still to be defined. The purpose of this review is to discuss recent insights into the biology of GrB and to evaluate its functional significance in health and disease.
Early Puberty: What Is Normal and When Is Treatment Indicated?
Authors: Ritzén E. Martin
Published: December 2003

Girls and boys who enter puberty before 8 and 9 years of age, respectively (corresponding to about –3 SDS), are arbitrarily considered to need referral for endocrine investigation. A recent report from the Lawson Wilkins Pediatric Endocrine Society suggested that the limit for investigation of girls and boys should be lowered to 7 and 8 years, respectively. For African-American girls, 6 years is the suggested age. This recommendation has been criticized. Although short stature is a common end result of precocious puberty, short- and long-term psychological symptoms may be more important, since several studies have indicated psychopathology in this patient group. Whether this can be prevented by gonadotropin releasing hormone agonist treatment remains to be shown. This review will highlight the psychological aspects of early puberty. In short, aspects other than height should also be evaluated when considering treatment of the early maturing child.
Ascertainment and Treatment of Delayed Puberty
Authors: Pozo Jesús , Argente Jesús
Published: December 2003

The majority of patients with pubertal delay, can be classified as having primary pubertal delay (constitutional delay of growth and puberty, CDGP), although any child with a chronic disease could present with delayed puberty. In contrast, children with hypogonadism, either hyper- or hypogonadotropic, exhibit a total absence of pubertal development. Hence, early evaluation of these patients should be performed. Delay of puberty leads to psychological problems, secondary to short stature and/or delay in the acquisition of secondary sex characteristics and the reduction of bone mass. Although the final height in patients with CDGP is usually normal, some of these patients do not reach the third percentile or remain in the lowest part of the growth chart according to familial height. The most common reason for treating CDGP patients, usually with sex steroids, is for psychological difficulties and for loss of bone mineralization. Treatment must be individualized. Therapeutic options and new drugs will be discussed. Appropriate treatment and adequate nutritional intake are indicated in patients with delayed puberty due to chronic illness. In patients with hypo- or hypergonadotropic hypogonadism, puberty must be induced or completed. Different treatments (GnRH analogues, gonadotropins and sex steroids), and the main objectives are discussed.
Comparative Study of the Sensitivity of Lymphoblastoid and Transformed Monocytic Cell Lines to the Cytotoxic Effects of Viscum album Extracts of Different Origin
Authors: Duong Van Huyen Jean-Paul , Delignat Sandrine , Kazatchkine Michel D. , Kaveri Srini V.
Published: December 2003

Viscum album (VA) preparations consist of aqueous extracts of V. album, the European mistletoe. VA extracts contain mistletoe lectins, which are members of the ribosome-inactivating protein type II family. VA preparations have cytotoxic and immunomodulatory properties. Cytotoxicity induced by VA extracts may differ greatly according to the origin of the preparation (host tree, fermented extract) and the cell type. This work was performed to assess the cytotoxicity of various VA preparations, i.e. VA Qu FrF, Qu Spez, M Spez and VA P, in lymphoblastoid and monocytic cell lines. VA Qu FrF, Qu Spez and M Spez induced dose-dependent cell death and inhibition of cell proliferation in lymphoblastoid T cell lines and in transformed monocytic lines. In contrast, the majority of B cell lines tested were resistant to cytotoxicity induced by VA extracts. While VA Qu FrF, Qu Spez and M Spez were potent inducers of cell death, extracts of VA P, derived from mistletoe plants growing on pine trees, failed to induce any cell death in any of the cell lines examined.
Association Study of a Brain-Derived Neurotrophic-Factor Genetic Polymorphism and Mood Disorders, Age of Onset and Suicidal Behavior
Authors: Hong Chen-Jee , Huo Sheue-Jane , Yen Feng-Chang , Tung Chun-Liang , Pan Guo-Mei , Tsai Shih-Jen
Published: December 2003

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth factor family, has been implicated in both mood disorders and suicidal behavior. This study has examined the association between the BDNF gene Val66Met polymorphism and mood disorders, age of onset and suicidal behavior in a Chinese sample population. The genotype and allele frequencies for the BDNF gene Val66Met polymorphism did not differ comparing depression groups (total, bipolar disorder or major depression) and control subjects. Furthermore, it was not demonstrated that this BDNF polymorphism was associated with age of onset or suicidal history in our mood disorder patients. Based on these results, it seems reasonable to suggest that this polymorphism is unlikely to play a major role in the genetic susceptibility to mood disorders. Given the fact that the positive association between BDNF gene Val66Met polymorphism and bipolar disorder has only been demonstrated for a Caucasian population but not for a Japanese analog or our Chinese sample, it appears likely that this association is ethnicity dependent.
Efficacy and Safety of Galantamine in Patients with Dementia with Lewy Bodies: A 12-Week Interim Analysis
Authors: Edwards Keith R. , Hershey Linda , Wray Laura , Bednarczyk Edward M. , Lichter David , Farlow Martin , Johnson Stewart
Published: December 2003

Observations on the neurochemistry of dementia with Lewy bodies (DLB) have suggested that cholinesterase inhibitors (ChEIs) might be beneficial in treating some clinical symptoms of DLB. A 24-week, multicenter open-label study was designed to assess the safety and efficacy of the ChEI galantamine in patients with DLB, and an interim analysis of results was performed at 12 weeks. Efficacy analyses were performed on data from 25 patients. Scores on the Neuropsychiatric Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks (marginally significant, p = 0.061). NPI-12 scores decreased by half in 12 of the 25 patients. Highly significant improvement was observed in scores on the NPI-4 subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores on the Clinician’s Global Impression of Change (CGIC) improved by 0.95 points (significant, p = 0.02). Improvements also were found in secondary efficacy variables, including cognitive, functional, activities of daily living, sleep and confusion assessments. Motor scores, as measured by the UPDRS motor subscale, showed mild improvement, which demonstrates that galantamine has no adverse effect on parkinsonian symptoms. Adverse events generally were transient and of mild-to-moderate intensity. Two of the 25 patients discontinued galantamine because of nausea and anorexia. One serious adverse event was recorded, but it was judged to be unrelated to the study medication.
Increase in Transglutaminase 2 in Idiopathic Inflammatory Myopathies
Authors: Choi Young-Chul , Kim Tai-Seung , Kim Soo-Youl
Published: December 2003

Idiopathic inflammatory myopathies (IMs), including dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (s-IBM), are characterized by inflammatory cell infiltration in muscle tissue and muscle fiber destruction, which leads to muscle weakness. Although the cause of IMs is unclear, an autoimmune pathogenesis may be involved in initiating the muscle inflammation. Recently, we have found an aberrant expression of transglutaminase 2 (TGase 2) in s-IBM, which is closely associated with insoluble inclusion body formation. TGase 2 is a cross-linking enzyme that generates a conformational change of molecules via a covalent isopeptide bond. The increase in the level of TGase 2 expression and the inappropriate presentation of substrates/cross-linked aggregates to the immune system may contribute to the autoimmune aspects of IMs. We investigated whether or not an increase in TGase 2 expression is a common factor in muscle inflammation. Duchenne muscular dystrophy (DMD) and normal tissues were employed as controls. Using immunocytochemistry and quantitative RT-PCR, the level of TGase 2 expression was found to be specifically increased in PM and DM, but not in DMD and normal controls. Therefore, the targeting of TGase inhibition in IMs will be a challenging therapeutic approach that should be investigated in the near future.