bluuebunny/crossref_metadata_2025 huggingface dataset:
Benzylthiouracil-Induced Glomerulonephritis
Authors: Trimeche Ajmi Sihem , Braham Rim , Toumi Sarra , Chadli Chaieb Molka , Maaroufi Amel , Ach Koussay , Chaieb Larbi
Published: July 2009

Vasculitis is a rare complication of antithyroid drugs (ATDs). It was first described with Propylthiouracil (PTU). We report a new case of antineutrophil cytoplasmic antibody (ANCA) vasculitis with glomerulonephritis induced by Benzylthiouracile (BTU). A 50-year-old man with Graves disease treated with BTU developed general malaise and haematuria without skin rash or respiratory involvement. Laboratory data revealed acute renal failure with proteinuria and haematuria. An indirect immunofluorescence test for ANCA was positive, showing a perinuclear pattern with specificity antimyeloperoxidase (MPO). A renal biopsy was performed and revealed pauci-immune extracapillary glomerular nephropathy and necrotic vasculitis lesions. Based on these findings we concluded to the diagnosis of rapidly progressive glomerulonephritis associated with ANCA induced by BTU therapy. The drug was therefore discontinued and the patient was treated with steroids and immunosuppressive treatment during 3 months. Renal failure, proteinuria and haematuria significantly improved within 2 months. However, P-ANCA remained positive until 10 months after drug withdrawal. Thyroid function was kept within normal range using iodine solution. We demonstrated clearly that BTU may induce severe forms of vasculitis with glomerulonephritis. Thus, the ANCA must be measured when confronted to systemic manifestation during treatment.
Some Identities of Symmetry for the Generalized Bernoulli Numbers and Polynomials
Authors: Kim Taekyun , Rim Seog-Hoon , Lee Byungje
Published: July 2009

By the properties ofp‐adic invariant integral onℤp, we establish various identities concerning the generalized Bernoulli numbers and polynomials. From the symmetric properties ofp‐adic invariant integral onℤp, we give some interesting relationship between the power sums and the generalized Bernoulli polynomials.
Collaborative Group Work in Middle Childhood
Authors: Howe Christine
Published: July 2009

Evidence exists that children’s understanding can be facilitated through collaborative group work with peers, but little is known about the underlying processes. When processes are discussed, they are typically assumed to involve the assimilation of superior ideas that are constructed jointly. However, the assimilation of joint constructions cannot provide a complete account, and recent work suggests that unresolved contradiction during group interaction may contribute. Research is reported that examines the balance between unresolved contradiction and joint construction, via analyses of collaborative group work where 8- to 12-year-old children explored motion down an incline, rates of cooling, and floating in water. Results are consistent with processes stimulated by unresolved contradiction, but not with the assimilation of joint constructions.
Regulation of the Hypothalamic-Pituitary-Adrenal Axis
Authors: Papadimitriou Anastasios , Priftis Kostas N.
Published: July 2009

Glucocorticoids (GCs) are essential for the maintenance of homeostasis and enable the organism to prepare for, respond to and manage stress, either physical or emotional. Cortisol, the principal GC in humans, is synthesized in the adrenal cortex. It is released in the circulation in a pulsatile and circadian pattern. GC secretion is governed by hypothalamus and pituitary. The hypothalamus senses changes in the external and internal environment that may disrupt the homeostatic balance of the organism (i.e. stressors), and responds by releasing corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from parvocellular neurons projecting from the paraventricular nucleus to the median eminence. These neurohormones are released into the anterior pituitary where they act synergistically via specific receptors (CRH-R1 and V1B receptor, respectively) to trigger the release of the adrenocorticotropic hormone (ACTH) from the corticotrope cells into the systemic circulation. In turn, ACTH exerts its actions on the adrenal cortex via specific receptors, type 2 melanocortin receptors (MC2-R), to initiate the synthesis of cortisol, which is released immediately into the systemic circulation by diffusion. Hypothalamic CRH and AVP, pituitary ACTH and adrenal GCs comprise the hypothalamic-pituitary-adrenal (HPA) axis. In this brief review, the HPA axis and the various factors that regulate its function are described.
Evaluation of the Hypothalamic-Pituitary-Adrenal Axis Function in Childhood and Adolescence
Authors: Chrousos George P. , Kino Tomoshige , Charmandari Evangelia
Published: July 2009

The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the maintenance of basal and stress-related homeostasis. The hypothalamus controls the secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary, which in turn stimulates the secretion of glucocorticoids from the adrenal cortex. Glucocorticoids, the final effectors of the HPA axis, regulate a broad spectrum of physiologic functions essential for life and exert their effects through their ubiquitously distributed intracellular receptors. Alterations in the activity of the HPA axis may present with symptoms and signs of glucocorticoid deficiency or excess. Detailed endocrinologic evaluation is of primary importance in determining the diagnosis and/or etiology of the underlying condition. We review the most common endocrinologic investigations used in the evaluation of the HPA axis integrity and function.
Glucocorticoid Receptor in Human Respiratory Epithelial Cells
Authors: Pujols Laura , Mullol Joaquim , Picado Cèsar
Published: July 2009

Inhaled and intranasal glucocorticoids (GCs) are the most common and effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, and asthma, and the respiratory epithelium is a primary target of GC anti-inflammatory actions. GC effects are mediated through the GC receptor (GR). In humans, one single GR gene gives rise to two main GR products, namely GRα and GRβ, which are subject to translational and posttranslational modifications. GRα is expressed in virtually all human cells and tissues, including respiratory epithelial cells, and – at least in vitro – is downregulated by GC. GRα mediates the anti-inflammatory actions of GC by activating transcription of anti-inflammatory genes through binding of GRα to glucocorticoid response elements (GRE) located in the promoter region of target genes, repressing transcription of proinflammatory genes through direct interaction between GRα and proinflammatory transcription factors, such as AP-1 and NF-κB (transrepression), and also by destabilizing the mRNA of proinflammatory mediators. GRβ acts as a dominant negative inhibitor of GRα-mediated transactivation and transrepression in certain in vitro studies with transfected cells. The GRβ message is expressed at low levels in numerous tissues and its protein is mainly expressed in inflammatory cells, although it has also been detected in airway epithelial cells. Increased GRβ expression has been reported in bronchial asthma and nasal polyposis, and after incubation of cells with certain proinflammatory stimuli. However, the role of GRβ in modulating GC sensitivity in vivo has been highly debated and is as yet unclear.
Stress and Airway Reactivity in a Murine Model of Allergic Airway Inflammation
Authors: Quarcoo David , Pavlovic Sanja , Joachim Ricarda A.
Published: July 2009

Airway reactivity is a phenomenon with vast clinical implications in children. The regulation of airway reactivity is influenced by local and central mechanisms. In airway diseases like bronchial asthma, the pathological regulation of the airway caliber causes symptoms like cough and dyspnea. Stress has long been considered a powerful manipulator in the physiological regulation of the airways. To explore potential mechanisms linking stress to the exacerbation of asthma, we developed an animal model that combines allergic airway inflammation and exposure to stress. This review summarizes the experimental data obtained in our and similar mouse models. First, we describe the innervation and neuromediators in the airways, next we analyze the occurrence of airway hyperresponsiveness, and then we explore the phenomenon of stress to finally connect all of the topics in a synopsis.
Cortisol Responses to Stress in Allergic Children: Interaction with the Immune Response
Authors: Buske-Kirschbaum A.
Published: July 2009

Allergic manifestations are increasingly common in infants and children. Accumulating evidence suggests that the ‘epidemic’ increase of childhood allergy may be associated with environmental factors such as stress. Although the impact of stress on the manifestation and exacerbation of allergy has been demonstrated, the underlying mechanisms of stress-induced exacerbation are still obscure. A growing number of studies have suggested an altered hypothalamus-pituitary-adrenal (HPA) axis function to stress in allergic children. It is speculated that a dysfunctional HPA axis in response to stress may facilitate and/or consolidate immunological aberrations and thus, may increase the risk for allergic sensitization and exacerbation especially under stressful conditions. In the present review the potential impact of a hyporesponsive as well as a hyperresponsive HPA axis on the onset and chronification of childhood allergy is summarized. Moreover, potential factors that may contribute to the development of an aberrant HPA axis responsiveness in allergy are discussed.
Endocrine-Immune Interactions in Adrenal Function of Asthmatic Children on Inhaled Corticosteroids
Authors: Priftis Kostas N. , Papadimitriou Anastasios , Anthracopoulos Michael B. , Fretzayas Andrew , Chrousos George P.
Published: July 2009

The present review highlights adrenal function in the context of endocrine-immune interactions and hypothalamic-pituitary-adrenal (HPA) axis activity in asthmatic children on long-term treatment with inhaled corticosteroids (ICS). Activation of the HPA axis by specific cytokines increases the release of cortisol, which in turn feeds back and suppresses the immune reaction. Reduced responsiveness of the HPA axis in patients with various chronic allergic inflammatory disorders and a blunted HPA axis response of poorly controlled asthmatics before long-term treatment with ICS have been reported. It appears that pro- and anti-inflammatory cytokines may be involved in the attenuation of cortisol and ACTH responses to stress in these patients. ICS as anti-inflammatory agents may have favorable effects in asthmatics with baseline subnormal adrenal responses, thus improving adrenal function during successful long-term treatment; on the other hand, few patients on conventional doses may experience further deterioration of adrenal function, a phenomenon that most likely is genetically determined. When ICS are administered at high doses, secondary adrenal insufficiency due to the excessive exogenous corticosteroid certainly may become manifest.
Single Nucleotide Polymorphisms Related to HPA Axis Reactivity
Authors: DeRijk Roel H.
Published: July 2009

A very important question in the neuroendocrinology of stress-related disorders is why some individuals thrive and others break down under similar adverse conditions. The hypothalamic-pituitary-adrenal (HPA) axis is the central component of the stress system, displaying extensive variability in reactivity among human subjects. Common gene variants have been associated with several changes in HPA axis reactivity. These gene variants are identified in the GABAA receptor, the μ-opioid receptor, the serotonin transporter, catechol O-methyltransferase (COMT), monoamine oxidase (MAOA), the α2-adrenergic receptor, brain-derived neurotrophic factor and the anginotensin-converting enzyme. Most extensively studied are genetic variants of the two central corticosteroid receptors, the high-affinity mineralocorticoid receptor (MR) and the lower-affinity glucocorticoid receptor (GR). In the GR, the TthIIII, NR3C1-1, ER22/23EK, N363S, BclI and the A3669G, and in the MR, the –2 G/C and the I180V all modify HPA axis responsiveness at several levels. As a result of these genetic variants, HPA axis reactivity will be changed exposing not only the brain but the whole body to suboptimal cortisol levels during challenges. We propose that these genetic variants which modulate HPA axis reactivity are part of the genetic makeup that determines individual stress responsivity and coping style, affecting vulnerability to disease.
Intranasal Corticosteroids and Adrenal Suppression
Authors: Bruni Francesca Maria , De Luca Giuseppina , Venturoli Vico , Boner Attilio Loris
Published: July 2009

Allergic rhinitis is a common condition that frequently coexists with asthma and atopic dermatitis. It is commonly treated with intranasal corticosteroids which may increase the potential inception of side effects of the same type of drugs used for the treatment of other allergic diseases. A method to assess the systemic effect of corticosteroids is the evaluation of their effect on the hypothalamic-pituitary-adrenal (HPA) axis. However, it is not clear which test is best for detection of clinically relevant HPA axis suppression in children Morning plasma cortisol levels are twice that of late afternoon and evening values and a delay in the time of onset in peak cortisol levels has been observed in children treated with inhaled corticosteroids. Single morning cortisol level has a low sensitivity for detecting adrenal insufficiency in children. 24-Hour plasma cortisol is a good test because it is a non-invasive measure of the biologically active free cortisol levels for the entire day. For research purposes, the 24-hour integrated concentration plasma cortisol test is preferred. Studies that have looked at HPA axis suppression with intranasal corticosteroids indicate that overall, intranasal corticosteroids have a minimal effect on the HPA axis. A review of the literature reveals one study in which there was a decreased output of urinary cortisol during treatment with either budesonide or fluticasone propionate in adults. Other studies with fluticasone propionate or budesonide have shown no effect on the HPA axis in children. Beclomethasone dipropionate was shown to affect urinary cortisol output in one study on healthy volunteers. However, in a long-term study in children, no effect on the HPA axis was found. Mometasone furoate has been extensively studied in more than 20 trials of adults and children. No effects on the HPA axis were detected in either children or adults. Fluticasone furoate nasal spray was not associated with HPA axis suppression. It is unlikely that children are more sensitive to corticosteroids than adults. There is no reason to perform routine monitoring of adrenal function in children who are treated with intranasal corticosteroid unless those drugs are used concomitantly with inhaled corticosteroids and/or steroid ointments for the possible concomitant presence of asthma and/or atopic dermatitis.
Suppression of Dendritic Cells by HMGB1 Is Associated with Lymph Node Metastasis of Human Colon Cancer
Authors: Kusume Akiko , Sasahira Tomonori , Luo Yi , Isobe Mamoru , Nakagawa Naoya , Tatsumoto Naokuni , Fujii Kiyomu , Ohmori Hitoshi , Kuniyasu Hiroki
Published: July 2009

High mobility groupbox-1 (HMGB1) is a multifunctional cytokine secreted by cancer cells, which accelerates cell growth, invasion and angiogenesis in cancer, and induces apoptosis in macrophages. Thioglycolate-stimulated mouse peritoneal macrophages were induced to differentiate into dendritic cells by co-treatment with IL-4 and GM-CSF. The number of mouse peritoneal macrophage-derived dendritic cells (PMDDCs) showed a dose-dependent decrease in hrHMGB1 treatment. HMGB1-treated PMDDCs showed obvious apoptosis and increased the level of phosphorylated JNK. Intraperitoneal administration of HMGB1 decreased CD205-positive splenic dendritic cells in C57BL mice. To confirm the HMGB1-induced inhibitory effect on dendritic cells, 16 cases of human colon cancer invaded into the subserosal layer were examined. The 8 nodal metastasis-positive cases showed higher nodal HMGB1 concentrations (74 ± 23 vs. 41 ± 15 μg/ml, p = 0.0116) in lymph node tissues and lower CD205-positive nodal dendritic cell numbers (86 ± 22 vs. 137 ± 43/mm2, p = 0.0224) than those in the 8 metastasis-negative cases. Primary tumor tissues of metastasis-positive cases showed higher tumor HMGB1 levels (116 ± 33 vs. 37 ± 18 μg/ml, p = 0.0007) and lower CD205-positive intratumoral dendritic cell numbers (21 ± 13 vs. 62 ± 23 /mm2, p = 0.0068) than those in metastasis-negative cases. These findings suggest that HMGB1 produced by colon cancer cells suppressed nodal dendritic cells to disturb host anti-cancer immunity.
Timing of Expression of Inflammatory Mediators in Skeletal Muscles from Mice Acutely Infected with the RA Strain of Trypanosoma cruzi
Authors: Cutrullis Romina Andrea , Postan Miriam , Petray Patricia Beatriz , Corral Ricardo Santiago
Published: July 2009

Objective: Chagas’ disease is caused by persistent Trypanosoma cruzi infection in muscle cells that ultimately results in chronic inflammation and tissue destruction. The goal of this study was to determine the expression of different chemokines and their receptors, as well as proinflammatory cytokines and inducible nitric oxide synthase, in muscles from mice acutely infected with T. cruzi. Methods: Histological, semiquantitative reverse transcriptase polymerase chain reaction and immunohistochemical studies were performed on skeletal muscle and myocardium of BALB/c mice infected with T. cruzi, RA strain. Results: Early induction of muscular mRNA expression for CCL5/CCR5 and CXCL9/CXCR3, as well as for iNOS, IFN-γ, TNF-α and MIF, was demonstrated accompanied by progressive increases in parasitism and leukocyte recruitment. Protein overexpression for MIF and CCL5/CCR5 was also verified in the infected muscles. Conclusions: In muscles from acutely T. cruzi RA-infected mice, upregulated gene expression of proinflammatory chemokines, chemokine receptors, cytokines and iNOS is associated with the severity of parasite burden and myopathic alterations. Compared to the heart, striated muscles displayed differential timing of expression of several inflammatory mediators throughout acute infection. Our findings suggest that enhanced early production of these factors could contribute to T. cruzi-dependent inflammatory damage to skeletal muscles.
Inhibitor of Growth 4 Induces Growth Suppression and Apoptosis in Glioma U87MG
Authors: Li XiaoMei , Cai LiMin , Chen Hui , Zhang QingYuan , Zhang ShuJun , Wang YanHua , Dong YanYan , Cheng Hui , Qi JiPing
Published: July 2009

Objective: Inhibitor of growth (ING) 4 is a member of the ING family proteins. It has been shown to play an important role in cell cycle, transcription and oncogenesis, but the molecular mechanism of ING4 on tumor growth inhibition has not yet been elucidated. The goal of this study is to investigate the inhibitory effects of ING4 on gliomas and its mechanism by transduction of ING4 cDNA into glioma U87MG. Methods: The effect and mechanisms of ING4 on proliferation and apoptosis of U87MG were evaluated in vitro by MTT assay, flow-cytometric analysis, TUNEL assay, Western blot analysis and animal experiments. Results: The level of ING4 was markedly reduced in glioma tissues, and the extent of reduction correlated with the progression from lower to higher grades of tumors. It was observed that U87MG with exogenous ING4 gene presented with growth suppression, apoptosis enhancement and the deregulation of cell cycle- or apoptosis-regulating proteins. Conclusion: ING4 has a potential role on the growth suppression and apoptosis enhancement in gliomas U87MG via the activation of mitochondrial-induced apoptotic pathway and the hindrance of the cell cycle progression. The low expression and dysfunction of ING4 might be correlated with the tumorigenesis and progression of gliomas.
Thymidylate Synthase and Dihydropyrimidine Dehydrogenase Are Upregulated in Pancreatic and Biliary Tract Cancers
Authors: Shimoda Mitsugi , Sawada Tokihiko , Kubota Keiichi
Published: July 2009

Purpose: To investigate a rationale of pancreatobiliary cancers, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) concentrations in cancer tissues were evaluated. Patients and Methods: Twenty-nine patients with pancreatic cancer (PC) and 43 with biliary tract cancer (BTC; 27 cases of bile duct cancer, 8 of gallbladder cancer and 8 of cancer of the papillary area) were included. ELISA was used to assess the concentrations of TS and DPD in cancerous and noncancerous tissues. All 82 patients were followed up at least 12 months after surgery. We compared patient survivals between the 2 groups, taking TS and DPD cutoff as median values, high versus low DPD and high versus low TS in the cancerous tissue of PC and BTC patients. Results: As for PC, DPD and TS concentrations were significantly higher in cancerous than in noncancerous tissues (p = 0.016 vs. 0.036). In BTC, TS concentration was higher in cancerous than in noncancerous tissue (p = 0.0001). Patients with low TS and DPD concentrations had a tendency to have a better disease-free survival than those with high TS and DPD concentrations in PC groups; especially, BTC patients’ disease-free survival with high TS was significantly longer than that with low TS (p = 0.0083). Discussion: TS and DPD levels had a tendency to be high in PC and BTC cancerous tissues. High TS in the cancerous tissue was associated with better disease-free survival in BTC.
Increased Connective Tissue Extracellular Matrix in the op/op Model of Osteopetrosis
Authors: Radi Zaher A. , Guzman Roberto E. , Bell Rosonald R.
Published: July 2009

Mice that are homozygous for the recessive osteopetrosis spontaneous mutation (op/op) develop severe osteopetrosis due to a defect in the production of macrophage colony-stimulating factor (M-CSF) and a deficiency in monocyte-derived osteoclasts. Our study describes a novel soft tissue finding in an osteopetrosis (B6C3Fe a/a-Csf1op/J) mouse model. Tissues were obtained from B6C3Fe a/a-Csf1op/J mice and age-matched wild-type mice, processed for hematoxylin and eosin sections, and comprehensive light microscopic tissue evaluation was performed. Mutant mice had characteristic traits of op/op deficiency including missing incisors and domed skulls. Histologically, the bone marrow cavity was effaced by interweaving thick bony trabeculae consistent with osteopetrosis. An increase in a finely granular, basophilic interstitial extracellular matrix (ECM) was observed in the subcutaneous connective tissue of the op/op mice when compared with controls. Histochemically, the ECM was negative with periodic acid Schiff and stained dark blue with alcian blue at a pH of 2.5, indicating that it is composed primarily of nonsulfated glycosaminoglycans (GAGs). This work suggests an increased ECM that is composed mainly of GAGs located in the subcutaneous tissue in op/op mice. This increase in ECM may be related to altered matrix production or turnover because of changes in M-CSF production.
Ischemic Damage and Subsequent Proliferation of Oligodendrocytes in Hippocampal CA1 Region following Repeated Brief Cerebral Ischemia
Authors: Eda Hiro , Sato Shigeru , Sasaki Yoshihiro , Adachi Akiko , Ghazizadeh Mohammad
Published: July 2009

Changes in oligodendrocytes and astrocytes following repeated brief periods of ischemia were studied in gerbils. The repeated brief periods of cerebral ischemia were produced by occlusion of bilateral common arteries for 3 × 3 min at 1-hour intervals. Oligodendrocytes and astrocytes in hippocampal CA1 regions were examined on 1, 3, 7 and 14 days after ischemia. Seven days after ischemia reperfusion, astrocytes, large pale and small dark oligodendrocytes entered the necrotic pyramidal neuron layer and coexisted with microglia. The necrotic matter of neurons and phagolysosome was observed in cytoplasm of some large pale and small dark oligodendrocytes. Most oligodendrocytes also intermingled with reactive astrocytes. These reactive astrocytes showed glial fibrillary acidic protein-positive reaction. Furthermore, proliferating cell nuclear antigen-positive cells increased markedly 7 days after reperfusion. We conclude that the repeated brief cerebral ischemia caused proliferation of oligodendrocytes and astrocytes, and oligodendrocytes may play a phagocytic role for clearance of necrotic matter of neurons.
A Natural Tetrahydropyrimidine Protects Small Bowel from Cold Ischemia and Subsequent Warm in vitro Reperfusion Injury
Authors: Wei Lai , Wedeking Annika , Büttner Reinhard , Kalff Jörg C. , Tolba René H. , van Echten-Deckert Gerhild
Published: July 2009

Objective: Ischemia/reperfusion (I/R) injury is a major difficulty in small bowel transplantation. Many postoperative complications are caused by damage to the intestinal mucosa following organ retrieval and during cold storage. Here we investigate whether 1-, 4-, 5-, 6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid (THP) can protect ileal mucosa and muscularis against cold ischemia and subsequent warm in vitro reperfusion injury. Methods: Small rat bowels were stored in the absence or presence of THP or its synthetic derivative lauryl-THP for 18 h at 4°C. Several biochemical parameters were evaluated following isolated reperfusion in tissue grafts and/or effluent solution. Graft morphology was analyzed by electron microscopy. Ceramide was quantified as a potential target of THP action. Results: THP considerably inhibited apoptosis and improved all parameters illustrating membrane and subcellular integrity and functionality. Parallel studies with lauryl-THP failed to show a similar protective effect. Lauryl-THP, in contrast to THP, also failed to decrease tissue ceramide content, indicating the involvement of this well-known mediator of cellular stress response. Conclusions: THP effectively protects ileal mucosa and muscularis against ischemia and reperfusion injury, indicating for the first time the clinical relevance of this new and promising molecule that might become a central component in tissue and organ protection in the near future.
Aspects of Voice Irregularity Measurement in Connected Speech
Authors: Fourcin Adrian
Published: July 2009

Applications of the use of connected speech material for the objective assessment of two primary physical aspects of voice quality are described and discussed. Simple auditory perceptual criteria are employed to guide the choice of analysis parameters for the physical correlate of pitch, and their utility is investigated by the measurement of the characteristics of particular examples of the normal-speaking voice. This approach is extended to the measurement of vocal fold contact phase control in connected speech and both techniques are applied to pathological voice data.
Comparison of Acceleration and Impact Stress as Possible Loading Factors in Phonation: A Computer Modeling Study
Authors: Horáček Jaromír , Laukkanen Anne-Maria , Šidlof Petr , Murphy Peter , Švec Jan G.
Published: July 2009

Impact stress (the impact force divided by the contact area of the vocal folds) has been suspected to be the main traumatizing mechanism in voice production, and the main cause of vocal fold nodules. However, there are also other factors, such as the repetitive acceleration and deceleration, which may traumatize the vocal fold tissues. Using an aeroelastic model of voice production, the present study quantifies the acceleration and impact stress values in relation to lung pressure, fundamental frequency (F0) and prephonatory glottal half-width. Both impact stress and acceleration were found to increase with lung pressure. Compared to impact stress, acceleration was less dependent on prephonatory glottal width and, thus, on voice production type. Maximum acceleration values were about 5–10 times greater for high F0 (approx. 400 Hz) compared to low F0 (approx. 100 Hz), whereas maximum impact stress remained nearly unchanged. This suggests that acceleration, i.e. the inertia forces, may present at high F0 a greater load for the vocal folds, and in addition to the collision forces may contribute to the fact that females develop vocal fold nodules and other vocal fold traumas more frequently than males.
Automatic Detection of Laryngeal Pathologies in Records of Sustained Vowels by Means of Mel-Frequency Cepstral Coefficient Parameters and Differentiation of Patients by Sex
Authors: Fraile R. , Sáenz-Lechón N. , Godino-Llorente J.I. , Osma-Ruiz V. , Fredouille C.
Published: July 2009

Mel-frequency cepstral coefficients (MFCC) have traditionally been used in speaker identification applications. Their use has been extended to speech quality assessment for clinical applications during the last few years. While the significance of such parameters for such an application may not seem clear at first thought, previous research has demonstrated their robustness and statistical significance and, at the same time, their close relationship with glottal noise measurements. This paper includes a review of this parameterization scheme and it analyzes its performance for voice analysis when patients are differentiated by sex. While it is of common use for establishing normative values for traditional voice descriptors (e.g. pitch, jitter, formants), differentiation by sex had not been tested yet for cepstral analysis of voice with clinical purposes. This paper shows that the automatic detection of laryngeal pathology on voice records based on MFCC can significantly improve its performance by means of this prior differentiation by sex.
Voice Pathology Detection Based eon Short-Term Jitter Estimations in Running Speech
Authors: Vasilakis Miltiadis , Stylianou Yannis
Published: July 2009

In this paper, we investigate the use of jitter estimation over short time intervals (short-term jitter) for voice pathology detection in the case of running or continuous speech. Short-term jitter estimations are provided by the spectral jitter estimator (SJE), which is based on a mathematical description of the jitter phenomenon. The SJE has been shown to be robust against errors in pitch period estimations, which makes it a good candidate for measuring jitter in continuous speech. On two large databases of sustained vowel recordings from healthy and pathological voices, we suggest a threshold for the SJE for pathology detection based on cross-database validation. Applying that to a database of continuous speech (reading text) from normophonic and dysphonic speakers, a second threshold and new features are suggested for monitoring jitter in continuous speech. Detection performance of the suggested thresholds and features was evaluated using receiver operating characteristic curves and their discriminative efficiency between healthy and pathological voices was judged using the area under the curve index. In terms of area under the curve, the suggested features for reading text provide a discrimination score of about 95%, while the second threshold provides a classification rate of 87.8%. Furthermore, estimated short-term jitter values from reading text were found to confirm the studies showing a decrease of jitter with increasing fundamental frequencies, and the more frequent presence of high jitter values in the case of pathological voices as time increases.
Pathogenesis of Vocal Fold Nodules: New Insights from a Modelling Approach
Authors: Dejonckere Philippe H. , Kob Malte
Published: July 2009

Objective: To give new insights into the pathogenesis of vocal fold nodules: (a) why the female/male ratio is so extreme, (b) how an hourglass-shaped vibration pattern – eliciting a localized microtrauma – originates, and (c) what the roles of muscular tension imbalance and of behavioral aspects are. Materials and Methods: Simulations with a 3-dimensional computer model of the vibrating vocal folds. Results and Conclusion: (1) A slightly incomplete dorsal vocal fold adduction is a first condition for inducing an hourglass vibration pattern. (2) A limited collision zone is only possible with a small degree of curving of the rest position of the vocal fold edges in their ventral portion. This is an anatomical characteristic of the adult female larynx. Muscular fatigue and resulting hypotonia seem to enhance this curving. (3) If both these conditions are fulfilled, a sufficient vibration amplitude is required to achieve a localized impact. (4) This third condition can be obtained by an increased subglottal pressure and/or by a decrease in active stress of the tension forces between the neighboring vocalis masses. These last aspects incorporate muscular tension imbalance (dyskinesia) and behavioral aspects in the modelling process. Decrease in active stress is a possible effect of fatigue, and increase in subglottal pressure a result of effort compensation.
Objective Acoustic-Phonetic Speech Analysis in Patients Treated for Oral or Oropharyngeal Cancer
Authors: de Bruijn Marieke J. , ten Bosch Louis , Kuik Dirk J. , Quené Hugo , Langendijk Johannes A. , Leemans C. René , Verdonck-de Leeuw Irma M.
Published: July 2009

Objective: Speech impairment often occurs in patients after treatment for head and neck cancer. New treatment modalities such as surgical reconstruction or (chemo)radiation techniques aim at sparing anatomical structures that are correlated with speech and swallowing. In randomized trials investigating efficacy of various treatment modalities or speech rehabilitation, objective speech analysis techniques may add to improve speech outcome assessment. The goal of the present study is to investigate the role of objective acoustic-phonetic analyses in a multidimensional speech assessment protocol. Patients and Methods: Speech recordings of 51 patients (6 months after reconstructive surgery and postoperative radiotherapy for oral or oropharyngeal cancer) and of 18 control speakers were subjectively evaluated regarding intelligibility, nasal resonance, articulation, and patient-reported speech outcome (speech subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 module). Acoustic-phonetic analyses were performed to calculate formant values of the vowels /a, i, u/, vowel space, air pressure release of /k/ and spectral slope of /x/. Results: Intelligibility, articulation, and nasal resonance were best predicted by vowel space and /k/. Within patients, /k/ and /x/ differentiated tumor site and stage. Various objective speech parameters were related to speech problems as reported by patients. Conclusion: Objective acoustic-phonetic analysis of speech of patients is feasible and contributes to further development of a speech assessment protocol.
Clinical and Molecular Features of Type 1 Pseudohypoaldosteronism
Authors: Riepe Felix G.
Published: July 2009

Pseudohypoaldosteronism (PHA) is a rare heterogeneous syndrome of mineralocorticoid resistance causing insufficient potassium and hydrogen secretion. PHA type 1 (PHA1) causes neonatal salt loss, failure to thrive, dehydration and circulatory shock. Two different forms of PHA1 can be distinguished on the clinical and genetic level, showing either a systemic or a renal form of mineralocorticoid resistance. This review provides an overview on transepithelial sodium reabsorption and on clinical features and the underlying molecular pathology of systemic and renal PHA1 caused by mutations in the subunit genes (SCNN1A, SCNN1B, SCNN1G) of the epithelial sodium channel (ENaC) and the mineralocorticoid receptor coding gene NR3C2. The in vitro investigation of several mutants has resulted in important progress in the understanding of the physiology of ENaC and the mineralocorticoid receptor. Some mutations are discussed in more detail to demonstrate some of these findings. A better clinical work-up of the patients suffering from PHA1 may delineate additional associations between the genotype and phenotype in the future.
The IGF-I Response to Growth Hormone Is Related to Body Mass Index in Short Children with Normal Weight
Authors: Roman Rossana , Iniguez German , Lammoglia Juan Javier , Avila Alejandra , Salazar Teresa , Cassorla Fernando
Published: July 2009

Aim: We investigated whether the insulin-like growth factor (IGF)-I response to growth hormone (GH) is regulated by body mass index (BMI) in short children with normal weight. Methods: We studied 37 prepubertal children with idiopathic short stature (ISS), comparing children with high-normal BMI (standard deviation scores, SDS 1.23 ± 0.11, n = 20) and low-normal BMI (SDS –0.93 ± 0.12, n = 17). The IGF-I response to GH was determined with an abbreviated IGF-I generation test, by measuring serum IGF-I concentrations at baseline and 24 h after the administration of GH (0.033 mg/kg). Results: Children with high- and low-normal BMI had similar age (8.5 ± 0.7 vs. 8.7 ± 0.7 years) and height (–2.0 ± 0.1 vs. –2.2 ± 0.2 SDS). However, children with high-normal BMI exhibited higher mean basal IGF-I (191 ± 15 vs. 139 ± 11 ng/ml, p < 0.05), higher mean IGF-I levels 24 h after GH administration (261 ± 22 vs. 164 ± 14 ng/ml, p < 0.05) and a higher IGF-I percent increase after GH administration (37 ± 5 vs. 17 ± 4%, p < 0.05) compared with children with normal-low BMI. Conclusion: BMI modulates the IGF-I response to GH, suggesting that GH sensitivity may be influenced by the nutritional status in children with ISS and normal body weight.
Birth Size, Postnatal Growth and Growth during Growth Hormone Treatment in Small-for-Gestational-Age Children: Associations with IGF1 Gene Polymorphisms and Haplotypes?
Authors: Ester Wietske A. , van Meurs Joyce B. , Arends Nicolette J. , Uitterlinden André G. , de Ridder Maria A. , Hokken-Koelega Anita C.
Published: July 2009

Background: Short small-for-gestational-age (SGA) children experience pre- and postnatal growth restriction, which might be influenced by polymorphisms in the IGF1 gene. The well-known –841(CA)n/192 bp polymorphism has been associated with birth size and cardiovascular disease. Aims: To determine whether birth size, postnatal growth and growth during growth hormone (GH) treatment, were associated with IGF1 gene polymorphisms and haplotypes. Methods: 201 short SGA children were investigated for four IGF1 gene polymorphisms in the promoter (–G1245A, –841(CA)n), intron 2 (+3703(CT)n) and 3UTR (+A1830G). Spontaneous growth and growth during GH treatment were studied. Results: The –1245 A allele was identified as a marker-allele for the well-known –841(CA)n/non-192 bp allele, both part of haplotype 2. The –1245 A allele was not associated with head circumference at birth, but was associated with a postnatal 0.3 SDS smaller head circumference at age 1–3. The –1245 A allele was also associated with a 1-week shorter gestational age which explained the association with a smaller absolute birth size. No associations were found with gestational age-adjusted birth size, height and weight SDS during postnatal life and with growth during GH treatment. Conclusions: The –G1245A SNP appeared to be a marker for the well-known –841(CA)n/192 bp polymorphism. Haplotype 2, of which the –1245 A allele was the marker, was associated with a smaller head circumference SDS during spontaneous postnatal growth, but not during GH treatment.
Regulatory Effect of Common Promoter Polymorphisms on the Expression of the 11β-Hydroxysteroid Dehydrogenase Type 1 Gene
Authors: Ku Yun Hyi , Koo Bo Kyung , Kwak Soo Heon , Cho Young Min , Shin Hyoung Doo , Lee Hong Kyu , Kim Yeonjung , Choi Jung-Won , Oh Bermseok , Park Kyong Soo
Published: July 2009

Background/Aims: Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to active cortisol, has become an emerging therapeutic target for type 2 diabetes mellitus and obesity. In this study, we examined the association between HSD11B1 polymorphisms and type 2 diabetes and metabolic phenotypes in Koreans. Methods: We sequenced all exons including exon-intron boundaries and the promoter region of the HSD11B1 gene. Of 8 polymorphisms identified, we selected 4 common single-nucleotide polymorphisms (g.–19835G>A, g.–19609A>G, g.+27447G>C and g.+27810C>T) based on location, linkage disequilibrium and frequency and which were genotyped in 757 subjects with type 2 diabetes and 644 nondiabetic subjects. Results: There was no association between the 4 common polymorphisms of HSD11B1 and type 2 diabetes. g.–19835G>A and g.–19609A>G showed modest associations with fasting plasma glucose and body mass index but the significance of these associations was lost after adjustment for multiple comparison. With regard to promoter polymorphisms in the HSD11B1 gene, a haplotype construct carrying both g.–19835A and g.–19609G showed significantly decreased promoter activity compared to other common haplotype constructs. Conclusion: The variations in HSD11B1 were not associated with susceptibility to type 2 diabetes or metabolic phenotypes in Koreans. However, the common promoter variants of the gene might exert a polymorphic regulatory effect on HSD11B1 expression.
Plasma Visfatin Concentrations in Subjects with Type 1 Diabetes Mellitus
Authors: Toruner F. , Altinova A.E. , Bukan N. , Arslan E. , Akbay E. , Ersoy R. , Arslan M.
Published: July 2009

Background/Aims: Visfatin is a recently discovered adipokine, and its circulating concentrations have not been adequately studied in type 1 diabetes mellitus (DM). Therefore, this study was designed to examine plasma visfatin levels in type 1 diabetic patients and to determine the relationships between visfatin and duration of diabetes, body mass index, glycemic control, insulin dosage and lipid profile. Methods: Forty-eight patients with type 1 DM and 26 healthy controls were investigated. Results: Type 1 diabetic patients had significantly low visfatin levels compared with controls (18.8 ± 1.7 vs. 20.2 ± 0.3 ng/ml; p < 0.0001). Visfatin levels were comparable between patients with a short duration of diabetes (<10 years) and patients with a long duration of diabetes (≥10 years) (18.9 ± 1.7 vs. 18.2 ± 2.0 ng/ml; p > 0.05). There was a significant correlation between visfatin and hemoglobin A1c (HbA1c) even after the adjustment for age, sex, body mass index and duration of diabetes (r = –0.48, p = 0.005) in the patient group. Multivariate analysis showed that significant determinants of visfatin concentrations were HbA1c and duration of diabetes (r2 = 0.27). Conclusion: These data emphasize that plasma visfatin concentrations are lower in patients with type 1 DM and related to glycemic control reflected by HbA1c.
Growth Hormone-Induced Increases in Skeletal Muscle Mass Alleviates the Associated Insulin Resistance in Short Children Born Small for Gestational Age, but Not with Growth Hormone Deficiency
Authors: Martin David D. , Schweizer Roland , Schönau Eckhard , Binder Gerhard , Ranke Michael B.
Published: July 2009

Purpose: To assess the effect of growth hormone (GH) treatment on body composition and insulin resistance, and the interdependence of these factors, in short children born small for gestational age (SGA) and children with growth hormone deficiency (GHD). Methods: In this longitudinal study we describe the relationship between changes in fasting hormone levels, and forearm cross-sectional fat/muscle area in 54 short children with GHD and 37 short children born SGA during the first 12 months of GH treatment. Mean GH dose was 31.4 μg/kg/day for GHD and 53.2 μg/kg/day for SGA. HOMA2-IR was calculated as a steady-state fasting measure of insulin resistance. Results: At baseline the SGA group displayed higher fasting glucose, insulin, C-peptide serum levels and higher HOMA2-IR (p < 0.01) than GHD patients despite similar low muscle mass and less fat mass. Both groups had low muscle mass for height, and mean changes in muscle, fat, insulin, C-peptide and HOMA2-IR during GH treatment were also similar. HOMA2-IR correlated positively with IGF-1 changes in both groups. In the SGA group, but not in the GHD group, the increase in fasting serum insulin, C-peptide and HOMA2-IR correlated negatively with increase in muscle mass (R2 = 0.32, p < 0.001) and decrease in fat mass (R2 = 0.12, p = 0.034). Conclusions: In SGA, unlike in GHD, the insulin resistance caused by GH treatment appears to be diminished by the GH-induced increase in muscle mass and decrease in fat mass.
Changes in Nocturnal Leptin and Insulin Concentrations in Prepubertal Low Birth Weight Children after Administration of the IGF-I/IGFBP-3 Complex
Authors: Iñiguez Germán , Román Rossana , Avila Alejandra , Gunn Ronald D. , Cassorla Fernando
Published: July 2009

Background: There is limited information regarding the effects of IGF-I and/or IGFBP-3 on circulating leptin concentrations. Aim: To determine the effects of IGF-I on leptin and insulin concentrations, we examined leptin and insulin nocturnal profiles before and after the administration of the IGF-I/IGFBP-3 complex (Iplex™) to prepubertal, low birth weight children. Methods: We studied 20 prepubertal children (11 boys and 9 girls), born after a full-term pregnancy with a mean birth weight below 2.8 kg. They were studied at the mean age of 7.3 ± 0.5 years (range 4–11 years). Their mean height was –1.8 ± 0.3 SDS and their mean BMI was 0.1 ± 0.2 SDS at the time of the study. The children were studied on 2 separate occasions, the first under basal conditions, and the second time after s.c. administration of 1 mg/kg of Iplex™ at 21.00 h. Blood samples for determination of leptin and insulin were obtained every 60 min between 23.00 h and 07.00 h, while the children were sleeping. In each patient, we calculated the leptin and insulin mean area under the curve, both under basal conditions and after the administration of the IGF-I/IGFBP-3 complex. Results: Mean nocturnal leptin area under the curve exhibited a significant increase (2.7 ± 2.1 vs. 11.2 ± 2.6 ng/ml h, p < 0.05), whereas that for mean insulin showed a slight decrease, which did not reach statistical significance after administration of the IGF-I/IGFBP-3 complex. Conclusion: These findings indicate that administration of the IGF-I/IGFBP-3 complex increases circulating leptin concentrations in short prepubertal, small for gestational age children, suggesting that IGF-I and/or IGFBP-3 may stimulate leptin secretion by adipose tissue.
Puberty Is Associated with a Marked Increase of the Female Sex Predominance in Chronic Autoimmune Thyroiditis
Authors: Mariotti Stefano , Prinzis Alessia , Ghiani Mariangela , Cambuli Valentina M. , Pilia Sabrina , Marras Valeria , Carta Daniela , Loche Sandro
Published: July 2009

Background: Chronic autoimmune thyroiditis (CAT) displays a strong female predominance with female-to-male (F:M) ratios of 4–20:1 in adults and 2–9:1 in children and adolescents. Both genetic and hormonal factors are involved in this phenomenon. The relation between puberty and F:M ratio in CAT has never been evaluated. Methods: The F:M ratio of 133 children with CAT (group A, age at diagnosis 2.4–17.7 years) was compared with that of 113 adult CAT patients (group B, age at diagnosis 21–79 years). Group A included 64 prepubertal (aged 2.4–13.2 years, group A1) and 69 pubertal (aged 9.2–17.4, group A2) children. Results: The F:M ratio in group A was 3.0, which is significantly (p < 0.001) lower than that (10.3) found in group B patients. The F:M ratio of group A1 prepubertal children was lower (1.6) and significantly different from that of pubertal (6.7, p < 0.01) and adult patients (10.3, p < 0.0001). This phenomenon was more evident in hypothyroid as compared to euthyroid CAT. Conclusions: This study provides the first evidence that female predominance of CAT strongly increases during puberty, suggesting a major role for sex hormones in this phenomenon. Further studies are needed to clarify this point.