bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Kinase C Is Involved in Arsenic Trioxide-Induced Apoptosis and Inhibition of Proliferation in Human Bladder Cancer Cells
Authors: Wang Yan , An Ruihua , Dong Xuesong , Pan Shangha , Duan Guowen , Sun Xueying
Published: March 2009

Objective: Arsenic trioxide (ATO) is a potent antitumor agent used to treat acute promyelocytic leukemia, and recently solid tumors including bladder cancers. However, a mechanism to explain its antitumor activity in bladder cancers is unclear. Here, we investigated the role of protein kinase C (PKC) in ATO-induced apoptosis and inhibition of proliferation in bladder cancer cells. Methods: T24 human bladder carcinoma cells were incubated with different concentrations of ATO in the presence or absence of PMA (PKC activator) or H7 (PKC inhibitor). Cell proliferation was assessed by MTT assay, and apoptosis by TUNEL and electron microscopy. Flow cytometry was used to analyze cell cycle distribution, radioimmunoassay to measure PKC activity, and Western blot analysis to detect caspase-3. Results: ATO inhibited proliferation and induced apoptosis of T24 cells in a dose-dependent manner, caused an increase of percentage of cells in the G1 phase and a decrease in the S and G2 phases, and upregulated the expression of activated caspase-3 and reduced PKC activity. These effects were abrogated by PMA, but enhanced by H7. Conclusions: PKC is involved in the anticancer activity of ATO for T24 bladder cancer cells, suggesting that targeting the PKC pathway may represent a potential approach to enhance the efficacy of ATO to treat bladder cancers.
Female Hydrocele: The Cyst of Nuck
Authors: Caviezel A. , Montet X. , Schwartz J. , Egger J.-F. , Iselin C.E.
Published: March 2009

The canal of Nuck is the portion of the processus vaginalis within the inguinal canal in women. A hydrocele of the canal of Nuck is equivalent to an encysted hydrocele of the cord in men. The literature reveals very little about this rare condition in the adult female patient. In this paper, we report a case of hydrocele of the canal of Nuck in a young female. The diagnosis was made with ultrasound and magnetic resonance imaging and then confirmed preoperatively and by histopathology. Although rare, a hydrocele of the canal of Nuck has to be included in the differential diagnosis of a groin lump in female patients.
Limitation of Brachial-Ankle Pulse Wave Velocity in Assessing the Risk of Stroke: Importance of Instantaneous Blood Pressure
Authors: Choi Jay Chol , Lee Jung Seok , Kang Sa-Yoon , Kang Ji-Hoon , Bae Jong-Myon , Lee Dae-Hie
Published: March 2009

Background and Objective: The carotid-femoral pulse wave velocity is a well-established index of aortic stiffness, and the brachial-ankle pulse wave velocity (baPWV) has recently been developed as a new method for evaluating arterial stiffness. However, whether the baPWV is also useful in evaluating the risk of stroke is currently controversial. Moreover, it is also unknown which types of stroke and neuroradiological findings are associated with increased arterial stiffness. We investigated the association between the baPWV and risk of stroke using a case-control design. Methods: This study enrolled 223 stroke patients (aged 65.6 ± 10.3 years, mean ± SD) and the same number of age- and sex-matched controls. All of the subjects in this study underwent a structured interview and had their vascular risk factors assessed. We reviewed brain magnetic resonance imaging and magnetic resonance angiography data of stroke patients to assessthe severity of white-matter hyperintensity lesions, number of cerebral microbleeds, and the stenosis of both intracranial and extracranial arteries. The baPWV was measured noninvasively by an oscillometric method. Results: The baPWV was most affected by the instantaneous systolic blood pressure, and was significantly higher in stroke patients than control subjects (1,721 ± 395 cm/s vs. 1,657 ± 366 cm/s, p = 0.03). However, the baPWV did not differ significantly with a specific type of stroke or subtype of ischemic stroke. Multiple regression analysis revealed that the baPWV was not independently associated with increased risk of stroke, or the severity of white-matter hyperintensity lesions or cerebral microbleeds. Conclusion: Although the baPWV was significantly higher in stroke patients than control subjects, it was not independently associated with increased risk of stroke or specific subtypes of ischemic stroke or neuroradiological findings.
Is the NIHSS Certification Process Too Lenient?
Authors: Hills Nancy K. , Josephson S. Andrew , Lyden Patrick D. , Johnston S. Claiborne
Published: March 2009

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) is a widely used measure of neurological function in clinical trials and patient assessment; inter-rater scoring variability could impact communications and trial power. The manner in which the rater certification test is scored yields multiple correct answers that have changed over time. We examined the range of possible total NIHSS scores from answers given in certification tests by over 7,000 individual raters who were certified. Methods: We analyzed the results of all raters who completed one of two standard multiple-patient videotaped certification examinations between 1998 and 2004. The range for the correct score, calculated using NIHSS ‘correct answers’, was determined for each patient. The distribution of scores derived from those who passed the certification test then was examined. Results: A total of 6,268 raters scored 5 patients on Test 1; 1,240 scored 6 patients on Test 2. Using a National Stroke Association (NSA) answer key, we found that correct total scores ranged from 2 correct scores to as many as 12 different correct total scores. Among raters who achieved a passing score and were therefore qualified to administer the NIHSS, score distributions were even wider, with 1 certification patient receiving 18 different correct total scores. Conclusions: Allowing multiple acceptable answers for questions on the NIHSS certification test introduces scoring variability. It seems reasonable to assume that the wider the range of acceptable answers in the certification test, the greater the variability in the performance of the test in trials and clinical practice by certified examiners. Greater consistency may be achieved by deriving a set of ‘best’ answers through expert consensus on all questions where this is possible, then teaching raters how to derive these answers using a required interactive training module.
High Resolution Wall and Lumen MRI of the Middle Cerebral Arteries at 3 Tesla
Authors: Ryu Chang-Woo , Jahng Geon-Ho , Kim Eui-Jong , Choi Woo-Suk , Yang Dal-Mo
Published: March 2009

Background: Although black-blood MRI (BB-MRI) can identify plaques in the cervical carotid arteries, this modality has not been applied in intracranial arteries. We imaged the lumina and walls of stenotic middle cerebral arteries (MCAs) in symptomatic and asymptomatic patients using high-resolution BB-MRI, in order to characterize vulnerable plaques and to determine the diagnostic accuracy of BB-MRI in MCA stenosis. Methods: Multicontrast (T1, T2 and proton density)-weighted BB-MRIs were acquired in 15 patients with MCA stenosis and in 2 volunteers. Each MCA was classified into one of three groups based on MR angiographic findings and symptoms: normal, symptomatic stenosis, or asymptomatic stenosis. The plaque signal intensity was interpreted and the total wall thickness was measured at the most stenotic segment. These values were then compared between asymptomatic and symptomatic MCAs using t test. For assessment of lumen imaging, the MCA stenosis graded on BB-MR images was compared with that graded on conventional angiography (digital subtraction angiography). Results: Twenty-eight MCAs were evaluated (normal MCAs: 12, symptomatic stenoses: 7, and asymptomatic stenoses: 9). T1- and/or T2-hyperintense foci were demonstrated more frequently within the plaques of symptomatic stenoses than within the plaques of asymptomatic stenoses (57.1 vs. 22%). The total wall thickness in the symptomatic stenoses was significantly higher than that seen in the asymptomatic stenoses. The stenosis grade for the BB-MRI was significantly correlated with the digital subtraction angiography grade. Conclusion: High-resolution, multicontrast-weighted BB-MRI has the potential to characterize atherosclerotic plaques in the MCA and may be a useful modality for evaluating the degree of stenosis.
Segment-Dependent Activation of Muscarinic Acetylcholine Receptor-Mediated [35S]Guanosine-5′-O-(γ-Thiotriphosphate) Binding in Airway Tissue Membranes
Authors: Hajek Peter , Ungemach Fritz Rupert , Abraham Getu
Published: March 2009

Muscarinic acetylcholine receptor (mAChR)-mediated guanine nucleotide-binding regulatory protein (G protein) activation and the functional interaction between receptors and the respective G proteins were investigated using an agonist-induced [35S]guanosine-5′-O-(γ-thiotriphosphate) ([35S]GTPγS)-binding approach in membranes of 3 native equine airway segments (trachea, bronchus and lung), which differ tremendously in mAChR density and subtype distribution; especially subtypes that couple negatively to adenylyl cyclase through Gi/0 proteins, i.e. M2 receptors. The assay was initially optimized by determining the influence of incubation time, guanosine 5′-diphosphate (GDP), MgCl2 and NaCl on basal and agonist-stimulated [35S]GTPγS binding. In standard assays, the presence of 10 μmol/l GDP, 10 mmol/l MgCl2 and 200 mmol/l NaCl increased carbachol-induced specific [35S]GTPγS binding in a segment- and receptor-density-dependent manner. Hereby, mAChR agonists stimulated [35S]GTPγS binding with a rank order of potency (oxotremorine M > carbachol > acetylcholine), and in a specific segment- and receptor-density-dependent manner (trachea > bronchus > lung). The increase in the specific [35S]GTPγS binding was potently inhibited by the mAChR antagonist atropine. Pertussis toxin and N-ethylmaleimide as Gi/0 protein ADP-ribosylating and alkylating agents reduced basal and agonist-stimulated [35S]GTPγS binding. The mAChR-stimulated [35S]GTPγS binding serves as a useful method for investigating the functional interaction between mAChRs and their respective G proteins in native airway tissue membranes of equines.
Patterns and Predictors of Long-Term Weight Change in Patients with Type 2 Diabetes Mellitus
Authors: Janghorbani Mohsen , Amini Masoud
Published: March 2009

This study describes patterns of long-term weight changes among patients with type 2 diabetes mellitus (DM) and identifies factors associated with weight changes. During the mean follow-up period of 9.1 (SD 3.6; range 1–15) years, 7,820 patients with type 2 DM have been examined to determine weight changes. Their weight at the last clinic visit was compared with that at the initial visit. The mean age of the participants was 51.3 (SD 10.5) years, with a mean DM duration of 6.1 (SD 5.6) years at initial registration. Mean weight change was –1.9% (95% confidence interval, CI –2.1 to –1.7) and varied according to the severity of baseline obesity (–4.1%; 95% CI –4.6 to –3.6) for normal weight, –8.9% (95% CI –13.0 to –4.8) for underweight, –1.7% (95% CI –2.1 to –1.3) for overweight and –0.3% (95% CI –0.03 to +0.73) for obese, and +0.2% (95% CI –1.8 to +2.1) for morbidly obese patients. Using a stepwise multiple regression model, higher body mass index, follow-up, fasting plasma glucose, systolic blood pressure, triglyceride level and treatment with insulin increased the percent weight change, and higher number of follow-up, cholesterol and smoking significantly decreased it. Although this Iranian patients with type 2 DM had negligible weight change over 9.1 years on average, several clinical and lifestyle characteristics were associated with weight change.
Undernutrition and Oxidative Stress as Risk Factors for High Blood Pressure in Older Mexican Adults
Authors: Mendoza-Núñez Víctor Manuel , Sánchez-Rodríguez Martha A. , Correa-Muñoz Elsa
Published: March 2009

Objective: To determine the relationship between undernutrition and oxidative stress as risk factors for high blood pressure (HBP) in older Mexican adults. We carried out a case-control study in a convenience sample of 62 older adults, 60–80 years of age; 32 without HBP (mean age 75.8 ± 5.1 years) and 30 with HBP (mean age 65.2 ± 6.8 years). Methods: We measured serum lipoperoxide (LPO) levels, antioxidant enzymes, total antioxidant activity and lipid profile; in addition, we evaluated the nutritional status with anthropometric measurements, the Mini Nutritional Assessment and food intake frequency. Data were analyzed with Student t and odds ratio (OR) statistical tests. Results: We observed significantly higher LPO levels in subjects with HBP than in normotensive subjects (0.303 ± 0.10 vs. 0.256 ± 0.06 μmol/l; p < 0.05). With respect to risk factors for HBP, we found an OR of 12.2 (95% CI 1.9–76.4, p < 0.01) in subjects with high LPO levels (≥0.320 μmol/l) and an OR of 5.0 (95% CI 1.1–23.0, p < 0.05) in those with undernutrition. Conclusion: Our findings suggest that high LPO levels and undernutrition are significant risk factors for HBP.
Survival and Re-Operation Rates after Neurosurgical Procedures in Scotland: Implications for Targeted Surveillance of Sub-Clinical Variant Creutzfeldt-Jakob Disease
Authors: Bird Sheila M. , Merrall Elizabeth L.C. , Ward Hester J.T. , Will Robert G.
Published: March 2009

Background/Aim: To assess the feasibility of post-mortem surveillance for subclinical variant Creutzfeldt-Jakob disease (vCJD) at least 5 years after neurosurgical procedures. Methods: Using Scottish record linkage, we estimated 5-year survival and re-operation rates after 4 neurosurgical procedures performed during 1993–2001 and identified as high or medium risk for transmitting vCJD: [B] drainage of extra- or subdural haematoma, [E] primary or revisional decompression operations and [H] creation of other ventricular shunts were classified as high risk; [C] operations on cerebral aneurysm (clipping) were classified as medium risk. Results: Fatality rate at 1 year depended strongly on procedure, weakly or not at all on sex and era, and increased with age. Procedure rates differed by sex. The rate of subsequent neurosurgical operations was highest for procedure [H] (sole: 21%; multiple: 28%). Conclusion: Each year, the UK has a new cohort of some 5,000 5-year survivors after a high- or medium-risk neurosurgical procedure, whose subsequent annual mortality is at least 3%. Even if half the surviving 5-year survivors of neurosurgery since 1996 gave consent-in-life for vCJD-informative testing at post-mortem, there would be too few relevant post-mortems in 2008–2010 (around 1,600) for ‘nil detections’ to exclude a 1 in 1,000 subclinical vCJD rate. Autopsy surveillance beyond 2010, or among 5-year survivors of non-neurosurgical at-risk operations, would be needed.
Pediatric Cavernous Malformation in the Central Nervous System: Report of 66 Cases
Authors: Xia Chengyu , Zhang Rong , Mao Ying , Zhou Liangfu
Published: March 2009

Objective: To investigate the clinical features and treatment outcome of pediatric cavernous malformation (CM) in the central nervous system. Patients and Methods: Retrospective review of clinical data and treatment outcome for 66 pediatric patients under the age of 18 treated for CM at Huashan Hospital within the past 10 years from January 1998 to December 2007. Results: In our consecutive series, the mean age at onset of the CM was 11.6 years (age from 15 months to 17.8 years), and the boy-to-girl ratio was 1.54:1 (40:26). Main initial clinical manifestations in cerebral CM (CCM) included: seizures (47.7%, 31/65), headache (46.2%, 30/65), intracranial hemorrhage (20%, 13/65), and focal neurological deficits (12.3%, 8/65). There were 59 children with single CM and 7 children with multiple CMs: 55 (83.3%) with supratentorial CM, 6 (9.1%) with infratentorial CM, 4 (6.1%) with supra- and infratentorial CM, and 1 (1.5%) with intramedullary CM. Sixty-two (93.9%; 62/64) children underwent microsurgical operations, and with the help of neuronavigation (19 cases), intraoperative ultrasonography (6 cases), and neuronavigation combined with intraoperative ultrasonography (3 cases). And 4 (6.1%; 4/66) children did not undergo any surgical intervention. There was no major morbidity or mortality from surgical procedures. Follow-up data of 50 children was available with a mean follow-up time of 39.1 months (range from 5 to 112 months), including 46 operated children and 4 children managed without operation. In the 46 operated children, the overall long-term post-treatment results were satisfactory: 73.9% no sign or symptom associated with CMs, 19.6% improved obviously, only 1 (2.2%) boy with unrestored paraplegia incurred by spinal cord CM, and 2 boys (4.3%) with controllable seizures occurring after initial 5 symptom-free years (one without need of antiepileptic drugs, AEDs). Of 24 children followed-up with preoperative seizures, only 1 boy needed therapeutic AEDs and the others did not need any after resections of the CMs. Three children managed without operations (2 with headache and 1 with seizures) had spontaneous disappearance of symptoms and stable intracerebral lesions at follow-up MRI images. Conclusions: For symptomatic solitary CM, the treatment of choice is complete microsurgical excision preceded by careful anatomical and functional evaluation, and the risk of operation can be decreased to lower level with the help of neuronavigation and intraoperative ultrasonography. For multiple CM, the treatment modalities must be considered cautiously. A much longer follow-up remains mandatory for appropriate treatment strategies.
Surgical Treatment of Myelomeningocele Carried Out at ‘Time Zero’ Immediately after Birth
Authors: Pinto Fernando Campos Gomes , Matushita Hamilton , Furlan André Luiz Beer , Alho Eduardo Joaquim , Goldenberg Dov Charles , Bunduki Victor , Krebs Vera Lúcia Jornada , Teixeira Manoel Jacobsen
Published: March 2009

Background/Aims: To present a protocol of immediate surgical repair of myelomeningocele (MMC) after birth (‘time zero’) and compare this surgical outcome with the surgery performed after the newborn’s admission to the nursery before the operation. Methods: Data from the medical files of 31 patients with MMC that underwent surgery after birth and after admission at the nursery (group I) were compared with a group of 23 patients with MMC admitted and prospectively followed, who underwent surgery immediately after birth – ‘at time zero’ (group II). Results: The preoperative rupture of the MMC occurred more frequently in group I (67 vs. 39%, p < 0.05). The need for ventriculoperitoneal shunt was 84% in group I and 65% in group II and 4 of them were performed during the same anesthetic time as the immediate MMC repair, with no statistically significant difference. Group I had a higher incidence of small dehiscences when compared to group II (29 vs. 13%, p < 0.05); however, there was no statistically significant difference regarding infections. After 1 year of follow-up, 61% of group I showed neurodevelopmental delay, whereas only 35% of group II showed it. Conclusions: The surgical intervention carried out immediately after the birth showed benefits regarding a lower incidence of preoperative rupture of the MMC, postoperative dehiscences and lower incidence of neurodevelopmental delay 1 year after birth.
Effect of Pioglitazone on Sciatic Nerve Ischemia/Reperfusion Injury in Rats
Authors: Rahimian Reza , Fakhfouri Gohar , Rasouli Mohammad R. , Nouri Mohsen , Nezami Behtash G. , Paydar Mehrak J. , Asadi-Amoli Fahimeh , Dehpour Ahmad Reza
Published: March 2009

Objective: Evaluation of the effect of pioglitazone on sciatic nerve ischemia/reperfusion (I/R) injury in rat. Method: Sixty rats were divided into 10 groups (n = 6). Treatment groups received 15 mg/kg pioglitazone intraperitoneally 1 h before induction of I/R by clamping the right common iliac and femoral arteries for 3 h. After certain time intervals of reperfusion (0 h, 3 h, 1, 4, and 7 days), the function of the hind limb was assessed using behavioral scores based on gait, grasp, paw position, and pinch sensitivity. The sciatic nerve was removed for light microscopy studies and graded for ischemic fiber degeneration (IFD) and edema. Plasma malondialdehyde (MDA) level was measured as an indicator of lipid peroxidation at the end of reperfusion intervals. Result: Behavioral scores were improved in the pioglitazone groups just on the 4th and 7th days of reperfusion (p < 0.05). Comparison of the pioglitazone with the control groups showed significant differences in edema at 4 and 7 days. Although IFD decreased in the pioglitazone group at 7 days of reperfusion, it was not statistically significant. In addition, the MDA level was significantly lower in pioglitazone-treated groups. Conclusion: Our results show the protective effect of pioglitazone on sciatic nerve I/R injury.
Modulation of Glycine Receptor Function by the Synthetic Cannabinoid HU210
Authors: Demir Reyhan , Leuwer Martin , de la Roche Jeanne , Krampfl Klaus , Foadi Nilufar , Karst Matthias , Dengler Reinhard , Haeseler Gertrud , Ahrens Jörg
Published: March 2009

Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. HU210 is a non-psychotropic, synthetic cannabinoid. As we hypothesized that non-CB receptor mechanisms of HU210 might contribute to its anti-inflammatory and anti-nociceptive effects we investigated the interaction of HU210 with strychnine-sensitive α1 glycine receptors by using the whole-cell patch clamp technique. HU210 showed a positive allosteric modulating effect in a low micromolar concentration range (EC50: 5.1 ± 2.6μmol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 μmol/l (EC50: 188.7 ± 46.2μmol/l). These in vitro results suggest that strychnine-sensitive glycine receptors may be a target for HU210 mediating some of its anti-inflammatory and anti-nociceptive properties.
Gamma Knife Stereotactic Radiosurgery for Low-Grade Astrocytomas
Authors: Henderson Mark A. , Fakiris Achilles J. , Timmerman Robert D. , Worth Robert M. , Lo Simon S. , Witt Thomas C.
Published: March 2009

Patients with low-grade astrocytoma (LGA; 8 pilocytic astrocytomas, 2 subependymal giant cell astrocytomas, 2 fibrillary astrocytomas) were selected for treatment with gamma knife stereotactic radiosurgery (GKSRS) based on having a demarcated appearance on CT or MRI and the possibility of dose sparing of adjacent eloquent structures. A median dose of 13 Gy was prescribed to the 50% isodose line, which covered the gross tumor. The median patient age was 17.4 years. The median target volume was 4.4 cm3. With a median follow-up of 48.2 months, 4-year tumor control and overall survival were 77 and 83%, respectively. Only 2 patients experienced symptomatic treatment-related toxicity. GKSRS can provide local control in cases of unresectable or recurrent LGA with a low incidence of side effects in carefully selected patients.
Endoscopic Resection of Advanced Anterior Skull Base Lesions: Oncologically Safe?
Authors: Cohen Marc A. , Liang Jonathan , Cohen Ian J. , Grady M. Sean , O’Malley, Jr. Bert W. , Newman Jason G.
Published: March 2009

Aims: (1) Learn if margins of resection in advanced anterior skull base tumors that are resected via endoscopic-assisted means are comparable with traditional craniofacial resection (CFR). (2) Understand the difference in patient morbidity with endoscopic surgery compared to traditional CFR. Methods: Retrospective review of 41 patients undergoing surgery for comparably staged advanced malignancies of the anterior skull base between 2000 and 2006. Eighteen patients underwent endoscopic surgery and 23 patients underwent traditional CFR for American Joint Committee on Cancer stage III, IV or Kadish stage C lesions of the paranasal sinuses and anterior skull base. Margins were evaluated and follow-up ranged from 3 months to 5 years. Results: Of the 18 patients undergoing endoscopic resections, margins were positive/close in 17% (3/18). Margins were positive/close in 17% (4/23) of patients undergoing CFR. Five complications were seen in 4/18 patients (22%) undergoing endoscopic surgery and 11 postoperative complications were seen in 7/23 patients (30%) undergoing CFR. Mean duration of hospitalization was 5.22 and 7.17 days for the endoscopic and CFR groups, respectively. Conclusions: There does not appear to be increased risk of positive margins in patients with advanced lesions undergoing endoscopic-assisted resection. Furthermore, the incidence of morbidity and duration of stay may be improved with endoscopic techniques.
Cervical Lymph Node Metastasis Model of Pyriform Sinus Carcinoma
Authors: Shen Na , Wu Haitao , Xu Xiuyin , Wang Jianzhong , Hoffman Matthew R. , Rieves Adam L. , Zhou Liang
Published: March 2009

Objective: To establish a cervical lymph node metastasis model of pyriform sinus VX2 carcinoma and investigate its metastatic features. Methods: VX2 tumor tissue suspension was transplanted into the pyriform sinus submucosa of 15 rabbits under direct laryngoscopy. Rabbits were randomly placed into 1 of 3 groups, each comprised of 5 rabbits. Health evaluation and histopathological analysis were performed on days 14 (group 1), 21 (group 2), and 28 (group 3) after transplantation. Results: VX2 tumors were transplanted successfully in all rabbits. Dysphagia, weight loss, rhinorrhea, and dyspnea were observed 28 days after transplantation. Deep cervical lymph node metastasis occurred in all rabbits at all time points. The rate of submandibular lymph node metastasis was 60% in group 1, 80% in group 2, and 100% in group 3. The rate of paratracheal lymph node metastasis was 0% in group 1, 80% in group 2, and 100% in group 3. Conclusions: A model of metastatic pyriform sinus carcinoma was established. This model could be used in future studies evaluating diagnostic and treatment methods.
Thyroid Disruption by Low-Dose BDE-47 in Prenatally Exposed Lambs
Authors: Abdelouahab Nadia , Suvorov Alexander , Pasquier Jean-Charles , Langlois Marie-France , Praud Jean-Paul , Takser Larissa
Published: March 2009

The purpose of this study was to evaluate whether polybrominated diphenyl ethers (PBDE) at levels reported for human populations affect the thyroid state in pregnant sheep and lambs. Pregnant sheep were exposed to vehicle or BDE-47 (0.2, 2 and 20 μg/kg b.w.) from the 5th to 15th week of gestation by intravenous injections weekly. Thyroid hormone levels and BDE-47 content in the blood of sheep and lambs and adipose tissue were analyzed. We observed a significant decrease in total T4 and T3 in exposed lambs without any effect in pregnant sheep. Our finding indicates that prenatal low-dose PBDE exposure results in PBDE storage in fat of offspring and can affect thyroid metabolism in the developing fetus.
Fertility-Sparing in Endometrial Cancer
Authors: Tangjitgamol Siriwan , Manusirivithaya Sumonmal , Hanprasertpong Jitti
Published: March 2009

Because endometrial cancer (EMC) patients frequently present at an early stage of disease, most have favorable outcomes, thus their quality of life after treatment is as important a consideration as a cure of cancer. This issue is especially important when EMC is encountered in younger or reproductive ages when the afflicted woman has not achieved her fertility function. It is a complicated situation when a physician encounters a request or question from a woman with EMC or her family concerning whether she could conceive a child prior to a definite cancer treatment. Despite being an interesting issue, there are only a few studies with definite treatment guidelines or any evidence-based recommendations concerning conservative treatment for EMC. Thus, we undertook this study to explore various considerations regarding the criteria and caveats for the management of EMC women who desire to preserve their fertility function. An algorithm guideline for conservative fertility treatment for EMC is also presented.
Cardiac Toxicity with Capecitabine, Vinorelbine and Trastuzumab Therapy: Case Report and Review of Fluoropyrimidine-Related Cardiotoxicity
Authors: Le Brun-Ly Valérie , Martin Jean , Venat-Bouvet Laurence , Darodes Nicole , Labourey Jean-Luc , Genet Dominique , Tubiana-Mathieu Nicole
Published: March 2009

A 45-year-old woman presented with a metastatic breast carcinoma and was treated with capecitabine, oral vinorelbine and trastuzumab combination therapy. The initial echocardiogram and the ECG were considered normal. She began treatment with 3-weekly cycles of the combination therapy. After the fourth dose of capecitabine, she presented with severe chest and arm pain, which was responsive to nitroglycerine spray. ECG at admission demonstrated tachycardia with ST-segment elevation suggesting ischemia. The clinical symptoms returned to baseline after a few hours and within 24 h the ECG showed inverted T in leads V3–V6. Cardiac ultrasonography revealed hypokinesia in the left ventricle without segmentary hypokinesia, with mildly reduced global systolic function, which normalized 1 week later. Two weeks later, she was rechallenged with capecitabine. After the fourth dose, the patient developed chest pain. ECG showed infero-apico-lateral injury, which normalized after administration of nitrates, nicorandil and verapamil and discontinuation of capecitabine. This case suggests that capecitabine can lead to the cardiotoxicity characteristic of other fluoropyrimidines. Therefore, it is important to inform patients about the risk of angina-like chest pain, to stop treatment immediately if symptoms occur, and to monitor the patient in hospital. Fluoropyrimidine rechallenge should be avoided because of the risk of ischemic event or sudden death.
Relationship between Gap Size and Dentine Secondary Caries Formation Assessed in a Microcosm Biofilm Model
Authors: Cenci M.S. , Pereira-Cenci T. , Cury J.A. , ten Cate J.M.
Published: March 2009

Secondary caries can develop at the tooth-restoration interface, depending on the presence of a gap and its size, but this process could be inhibited by fluoride. The aim of this study was to assess the relationship between gap size and dentine secondary caries adjacent to composite resin (CR) or glass ionomer (GI) restorations, using a microcosm biofilm model in a constant depth film fermentor (CDFF). Dentine discs restored with CR (Z250) or GI (Vitremer) with gap sizes of 0, 50, 100, 180 or 250 μm were mounted on the CDFF. Microcosm biofilms were formed on the restored discs and daily subjected to 8 pulses of 10% sucrose solution. On the 18th day, dentine mineral loss and lesion depth around the restorations were determined by transverse microradiography.The effect of gap size was overall not statistically significant either with regard to mineral loss (p = 0.449) or lesion depth (p = 0.328), but greater mineral loss and lesion depth were found adjacent to CR than to GI (p < 0.001). However, Spearman correlation showed that mineral loss and lesion depth increased with gap size for CR (p < 0.001) but not for GI (p > 0.05). The findings support the conclusion that fluoride released from GI inhibits dentine demineralization adjacent to restorations, irrespective of gap width.
The Effects of Acidic Fluoride Solutions on Early Enamel Erosion in vivo
Authors: Hjortsjö C. , Jonski G. , Thrane P.S. , Saxegaard E. , Young A.
Published: March 2009

Acidic fluoride solutions may reduce dental erosion. The aim of this study was to compare the effect of different acidic fluoride solutions on enamel dissolution using an established in vivo model. When possible 4 anterior teeth (255 teeth in a total of 67 subjects) were isolated and exposed to 0.01 M citric acid. The acid was collected in test tubes before (etch I) and 5 min after (etch II) application of test fluoride preparations. Acidic fluoride solutions (pH range 1.5–2.9), i.e. SnF2, TiF4 and hydrogen fluoride (HF) (all approx. 0.1 M F), HF (0.027, 0.055, 0.082 M F) and neutral NaF solution (0.1 M F) as control were applied to the labial surfaces of the teeth for 1 min (6 ml/min). Enamel dissolution was examined by chemical analysis of calcium content in the citric acid etch solutions using atom absorption spectrometry. The change in calcium concentration (ΔCa) and the percentage of mean calcium reduction were calculated from the difference in calcium loss between etch I and etch II. Statistical analysis was carried out using the Wilcoxon signed rank test and Kruskal-Wallis tests with Dunn’s multiple comparison. Results showed a mean ΔCa of 0.671 mg/l (SD 0.625) for SnF2, and ranged from 0.233 mg/l (SD 0.248) for the weakest HF solution to 0.373 mg/l (SD 0.310) for the strongest HF solution. This represented a 67% reduction in enamel dissolution for SnF2 and a 40–76% reduction for the HF solutions. No reduction was observed for TiF4 or NaF. The types of metal, pH and fluoride concentration are all important for the in vivo effect.
Effect of Fluoride on the Morphology of Calcium Phosphate Crystals Grown on Acid-Etched Human Enamel
Authors: Fan Y. , Sun Z. , Moradian-Oldak J.
Published: March 2009

The aim of this study was to examine the effect of fluoride ion concentration on the morphology of calcium phosphate crystals grown on acid-etched enamel as a model for tooth enamel erosion. Samples were immersed in calcification solution for 16 h and changes in crystal morphology were monitored by field emission scanning electron microscopy. Without fluoride, plate-like octacalcium phosphate crystals (20 nm thick, 2–10 μm wide) were formed. With 1–10 mg/l fluoride, arrays of denser needle-like nanocrystals (20–30 nm wide, >500 nm in length) were formed. We conclude that there is a minimal fluoride concentration (1 mg/l) that dramatically affects the morphology of calcium phosphate crystals grown on etched enamel in vitro.
Gastroesophageal Reflux Disease and Management in Advanced Pregnancy: A Prospective Survey
Authors: Fill Malfertheiner Sara , Malfertheiner Maximilian Valentin , Mönkemüller Klaus , Röhl Friedrich-Wilhelm , Malfertheiner Peter , Costa Serban-Dan
Published: March 2009

Background: Heartburn is known to be common during pregnancy, however validated data on gastroesophageal reflux disease (GERD) are missing. The aim of this survey was to study the prevalence of GERD, the frequency and severity of typical GERD symptoms, and their impact on quality of life and therapeutic management in advanced pregnancy. Methods: One hundred and thirty-five consecutive pregnant women in the third trimester were included in a prospective study using validated questionnaires: RDQ, QOLRAD and a self-administered questionnaire detailing sociodemographic factors. Results: The prevalence for GERD in this unselected population was 56.3%. Among symptoms regurgitation was the most frequent with 47.3%, whereas heartburn was graded as the most severe symptom. The impact of GERD on the QOL of the pregnant women was significant (p < 0.001). 22.9% of the GERD population required medication because of severe symptoms, often reported to be insufficient for symptoms relief. Conclusion: GERD is common in late pregnancy with an important negative impact on the QOL. GERD in advanced pregnancy deserves more attention and better therapeutic management.
A Prospective, Multicenter, Phase 2 Study of Imatinib Mesylate in Korean Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumor
Authors: Ryu Min-Hee , Kang Won Ki , Bang Yung-Jue , Lee Kyung Hee , Shin Dong Bok , Ryoo Baek-Yeol , Roh Jae Kyung , Kang Jin-Hyoung , Lee Hyoungnam , Kim Tae Won , Chang Heung Moon , Park Joon Oh , Park Young Suk , Kim Tae-You , Kim Min Kyoung , Lee Woon Kee , Kang Hye Jin , Kang Yoon-Koo
Published: March 2009

Objectives: This prospective, multicenter, phase 2 study evaluated the efficacy and safety of imatinib mesylate and assessed KIT and PDGFRA gene mutation status in Korean patients with gastrointestinal stromal tumors (GISTs). Methods: Forty-seven patients with pathologically proven KIT-positive metastatic or unresectable GISTs were accrued from eight institutions in Korea. Imatinib was administered orally at 400 mg once daily. In case of disease progression, the dose was escalated to 600 mg once daily, then 400 mg twice daily. KIT and PDGFRA mutations were analyzed in 29 of the 47 patients. Results: Imatinib produced partial responses in 30 patients (63.8%; 95% confidence interval, 50.1–77.6%) and stable disease in 13 patients (27.7%). The median time to response was 2.6 months (range, 1.0–6.2 months). With a median follow-up of 62 months (range, 32–67 months), 4-year progression-free survival and overall survival rates were 50 and 65%, respectively. The most common adverse events were anemia, neutropenia, edema, and skin rash (predominantly of grade 1–2). There were no treatment-related deaths. In the subset evaluated for mutational status, 24 patients (82.8%) had KIT exon 11 mutations and 1 (3.4%) had a KIT exon 9 mutation. Conclusions: Imatinib is effective and safe in Korean patients with metastatic or unresectable GIST.
Effect of Preceding Inspiratory Speed and End-Inspiratory Pause on Forced Expiratory Manoeuvre in Healthy Subjects and Chronic Obstructive Pulmonary Disease Patients
Authors: Boni Enrico , Chiari Stefania , Trigiani Marco , Gatta Diego , Pini Laura , Tantucci Claudio
Published: March 2009

Background: Lower peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) have been consistently found after slow inspiration with end-inspiratory pause (EIP). Objectives: It was the aim of this study to establish the respective influence of the speed of preceding inspiration (SPI) and EIP on the parameters obtained from the following expiratory forced vital capacity (FVC) manoeuvre. Methods: In 8 healthy subjects and 12 patients with chronic obstructive pulmonary disease (COPD), a number of inspirations with different SPI and EIP were performed. In the subsequent FVC manoeuvre, maximal expiratory flows, including PEF, and maximal expired volumes at different times, including FEV1, were measured. For each FVC manoeuvre, peak expiratory time, expired volume at PEF (as % of FVC), flow limitation by the negative expiratory pressure technique and FVC were checked to be sure of achieving a similar expiratory effort and starting inflation lung volume. Results: The highest values of PEF and FEV1 were found in normal subjects and COPD patients after fastest SPI without EIP (p < 0.001). In normal subjects, no significant PEF and FEV1 changes during FVC manoeuvre were observed with different SPI, in the absence of EIP. In contrast, inspirations with slower SPI (inspiratory time >2 s) without EIP were followed by lower PEF in COPD patients (p < 0.05). As compared with inspirations without EIP, those with a presence of EIP were invariably followed by lower PEF and FEV1, both in normal subjects and in COPD patients (p < 0.05). Conclusions: The effect of SPI on subsequent PEF and FEV1 is irrelevant in healthy subjects as well as in COPD patients, unless SPI is too slow (inspiratory time >2 s), while any EIP decreases these indices in all individuals.
Interaction of Aldosterone and Extracellular Volume in the Pathogenesis of Obesity-Associated Kidney Disease: A Narrative Review
Authors: Bomback Andrew S. , Klemmer Philip J.
Published: March 2009

Obesity and obesity-associated kidney injuries have played an important role in the rising prevalence of chronic kidney disease (CKD). The link between obesity and kidney disease begins with obesity’s well-known associations with diabetes and hypertension, the two leading etiologies of CKD. However, a growing body of evidence suggests that elevated aldosterone levels and expanded extracellular volume are key components of obesity-induced renal disease via aldosterone’s non-epithelial effects on the kidney. Highlighting these blood pressure- and diabetes-independent mechanisms of kidney injury in obesity allows an exploration of whether mineralocorticoid receptor blockade, coupled with weight loss and salt restriction, is an optimal treatment for overweight CKD patients.
Demographic, Clinical, and Psychological Characteristics of the Heartburn Groups Classified Using the Rome III Criteria and Factors Associated with the Responsiveness to Proton Pump Inhibitors in the Gastroesophageal Reflux Disease Group
Authors: Lee Kwang Jae , Kwon Heok Chun , Cheong Jae Yeon , Cho Sung Won
Published: March 2009

Background/Aims: The diagnostic criteria for nonerosive reflux disease (NERD) and functional heartburn (FH) have been changed. We investigated demographic, clinical, and psychological characteristics of the heartburn groups classified using the Rome III criteria and factors associated with the responsiveness to proton pump inhibitors (PPIs) in the gastroesophageal reflux disease (GERD) group. Methods: Ninety-five patients with heartburn underwent endoscopy, 24-hour esophageal pH-metry and then a PPI test. NERD was diagnosed when % time with pH <4 was >4%, a symptom index (SI) ≥50% or a positive PPI test in patients without erosive esophagitis. Patients without such findings were classified as FH. Results: Thirty-six patientshad erosive reflux disease (ERD), 36 had NERD, and 23 had FH. The proportion of males was significantly higher in ERD than in FH. Atypical symptoms and IBS were more prevalent in FH than in ERD. Anxiety was more prevalent in FH than in NERD. The prevalence of pathologic acid reflux, a positive SI and a positive PPI test was similar between ERD and NERD patients. In the ERD and NERD groups, depression was independently associated with nonresponsiveness to PPIs. Conclusions: FH is a different entity from ERD or NERD, particularly in terms of gender, acid reflux patterns, psychological profiles, and the responsiveness to PPIs.
Species Differences in the Relative Densities of D1- and D2-Like Dopamine Receptor Subtypes in the Japanese Quail and Rats: An in vitro Quantitative Receptor Autoradiography Study
Authors: Kleitz Hayley K. , Cornil Charlotte A. , Balthazart Jacques , Ball Gregory F.
Published: March 2009

Evidence has accumulated that the regulation of male sexual behavior by dopamine might not be the same in Japanese quail (and perhaps all birds) as it is in mammals. For example, the non-selective dopamine receptor agonist, apomorphine (APO), facilitates male sexual behavior in rats but inhibits it in quail. Although the general organization of the dopamine system is similar in birds and mammals, it is possible that the relative distribution and/or density of binding sites are different. We therefore compared the relative densities of D1-like and D2-like receptor subtypes in Japanese quail and rats, with the use of in vitro quantitative receptor autoradiography. Brain sections from 8 male rats and 8 male quail were labeled with [3H]SCH-23390 and [3H]Spiperone. In general we found a systematic species difference in the relative density of D1- vs. D2-like receptors such that the D2/D1 ratio is higher in quail than in rats in areas, known to be important target sites for dopamine action such as striatal regions or the preoptic area, which is also associated with activation of sexual behavior. This difference might explain the variation in the behavioral effectiveness of APO in rats as compared to quail; with a higher relative density of D2-like receptors in quail, a similar dose of APO would be more likely to activate inhibitory processes in quail than in rats.
Morphological Indicators of Olfactory Capability in Wobbegong Sharks (Orectolobidae, Elasmobranchii)
Authors: Theiss Susan M. , Hart Nathan S. , Collin Shaun P.
Published: March 2009

Elasmobranchs are thought to possess an acute sense of smell, but the relationship between the anatomy of their olfactory organs and their sensory ecology is poorly understood. Moreover, the ecological diversity of elasmobranchs as a group indicates that there might be considerable interspecific variation in the importance of the olfactory sense. Wobbegong sharks, with their sedentary lifestyle and ambush predatory technique, probably utilize their senses differently than other shark species, making it difficult to generalize about their olfactory capabilities and olfaction-dependent behaviors. In this study, the number of olfactory lamellae and the surface area of the olfactory epithelium were measured as a means of assessing relative olfactory sensitivity in four species of wobbegong shark (the Western wobbegong, Orectolobus hutchinsi; the spotted wobbegong, O. maculatus; the ornate wobbegong, O. ornatus; and the dwarf spotted wobbegong, O. parvimaculatus). We also present a phylogenetic comparative analysis between wobbegongs and other elasmobranchs for which published data on olfactory morphology are available. There is a significant difference in the total number of olfactory lamellae between most species, but not between O. hutchinsi and O. maculatus, although the olfactory sensory surface area is comparable between these two species and O. ornatus. Orectolobus parvimaculatus has a significantly larger olfactory sensory surface area than the other three species, and there is a positive relationship between total body length and olfactory sensory surface area for all four species. Assuming that these morphological measures are true indications of olfactory capability, the olfactory abilities of wobbegongs are as good as, or better than, other benthic elasmobranchs. Interspecific differences in olfactory ability within this group of benthic ambush predators could indicate relative differences in prey detection, intraspecific recognition and mate detection.
Family History as a Risk Factor for Early-Onset Stroke/Transient Ischemic Attack among Adults in the United States
Authors: Mvundura Mercy , McGruder Henraya , Khoury Muin J. , Valdez Rodolfo , Yoon Paula W.
Published: March 2009

Background: Stroke is a major cause of morbidity and death in the United States. We tested the association between familial risk for stroke and prevalence of the disease among US adults and assessed the use of family history of stroke as a risk assessment tool for the disease. Methods: Using data from the 2005 HealthStyles survey (n = 4,819), we explored the association between familial stroke risk (stratified as high, moderate or low) and the prevalence of stroke and related health conditions. We evaluated the clinical validity (sensitivity, specificity) of family history of stroke as an indicator of stroke risk. Stroke and the related medical conditions were self-reported. Results: Independent of other risk factors, people with a high familial risk for stroke were 4 times more likely to have had a stroke (95% confidence interval, CI, 2.6–6.0) than people with moderate or low familial risk. They were also 1.3 times (95% CI 1.1–1.6) more likely to have high blood pressure and 1.5 times (95% CI 1.3–2.0) more likely to have congestive heart failure. The sensitivity and specificity of using family history alone, high blood pressure alone or both risk factors to estimate stroke risk were 52 and 83%, 53 and 74%, and 29 and 95%, respectively. Conclusions: Despite several limitations typical of self-reported surveys, we find that in this sample of US adults, family history of stroke was significantly associated with the risk for stroke and high blood pressure as well as related conditions. Family history of stroke, alone or combined with other risk factors, can be a useful tool in assessing stroke risk among US adults.