bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel De Novo Mutation in Sulfonylurea Receptor 1 Presenting as Hyperinsulinism in Infancy Followed by Overt Diabetes in Early Adolescence
Authors: Abdulhadi-Atwan Maha , Bushman Jeremy D. , Tornovsky-Babaey Sharona , Perry Avital , Abu-Libdeh Abdulsalam , Glaser Benjamin , Shyng Show-Ling , Zangen David H. 
Published: April 2008

OBJECTIVE—Congenital hyperinsulinism, usually associated with severe neonatal hypoglycemia, may progress to diabetes, typically during the 4th decade of life in nonpancreatectomized patients. We aimed to genotype the ATP-sensitive K+ channel in a 10.5-year-old girl presenting with overt diabetes following hyperinsulinism in infancy.
RESEARCH DESIGN AND METHODS—A female aged 10.5 years presented with new-onset, antibody-negative diabetes (A1C 10.6%). She was born large for gestational age (5 kg) to a nondiabetic mother and developed frequent hypoglycemic episodes, which persisted until age 3 years and responded initially to intravenous glucose and later to oral sweets. Currently, she is fully pubertal and obese (BMI 30.2 kg/m2), with a partially controlled convulsive disorder (since age 1 year) and poor school performance. Glucose levels were &gt;11.1 mmol/l throughout 72 h of continuous glucose monitoring, with low insulin secretion during intravenous glucose tolerance testing. KCNJ11 and ABCC8 mutation analysis was performed, and the mutation identified was characterized in COSm6 cells.
RESULTS—A novel, de novo heterozygous ABCC8 sulfonylurea receptor (SUR)1 mutation (R370S) was identified in the patient's DNA but not in that of either parent. Cotransfection of Kir6.2 and mutant SUR1 demonstrate that the mutated protein is expressed efficiently at the cell surface but fails to respond to MgADP, resulting in minimal channel activity. Interestingly, the heterozygous channel (WT:R370S) responded well to glibenclamide, a finding that lead to the successful initiation of sulfonylurea therapy.
CONCLUSIONS—This new ABCC8 mutation is associated with neonatal hyperinsulinism progressing within 10 years to insulinopenic diabetes. Consistent with in vitro findings, the patient responded to sulfonylurea treatment. The mechanism causing the relatively rapid loss in β-cell function is not clear, but it may involve mutation-induced increased β-cell apoptosis related to increased metabolic demand.
Effect of Oral Amino Acids on Counterregulatory Responses and Cognitive Function During Insulin-Induced Hypoglycemia in Nondiabetic and Type 1 Diabetic People
Authors: Rossetti Paolo , Porcellati Francesca , Busciantella Ricci Natalia , Candeloro Paola , Cioli Patrizia , Nair K. Sreekumaran , Santeusanio Fausto , Bolli Geremia B. , Fanelli Carmine G. 
Published: April 2008

OBJECTIVE—Amino acids stimulate glucagon responses to hypoglycemia and may be utilized by the brain. The aim of this study was to assess the responses to hypoglycemia in nondiabetic and type 1 diabetic subjects after ingestion of an amino acid mixture.
RESEARCH DESIGN AND METHODS—Ten nondiabetic and 10 diabetic type 1 subjects were studied on three different occasions during intravenous insulin (2 mU · kg−1 · min−1) plus variable glucose for 160 min. In two studies, clamped hypoglycemia (47 mg/dl plasma glucose for 40 min) was induced and either oral placebo or an amino acid mixture (42 g) was given at 30 min. In the third study, amino acids were given, but euglycemia was maintained.
RESULTS—Plasma glucose and insulin were no different in the hypoglycemia studies with both placebo and amino acids (P &gt; 0.2). After the amino acid mixture, plasma amino acid concentrations increased to levels observed after a mixed meal (2.4 ± 0.13 vs. placebo study 1.7 ± 0.1 mmol/l, P = 0.02). During clamped euglycemia, ingestion of amino acids resulted in transient increases in glucagon concentrations, which returned to basal by the end of the study. During clamped hypoglycemia, glucagon response was sustained and increased more in amino acid studies versus placebo in nondiabetic and diabetic subjects (P &lt; 0.05), but other counter-regulatory hormones and total symptom score were not different. β-OH-butyrate was less suppressed after amino acids (200 ± 15 vs. 93 ± 9 μmol/l, P = 0.01). Among the cognitive tests administered, the following indicated less deterioration after amino acids than placebo: Trail-Making part B, PASAT (Paced Auditory Serial Addition Test) (2 s), digit span forward, Stroop colored words, and verbal memory tests for nondiabetic subjects; and Trail-Making part B, digit span backward, and Stroop color tests for diabetic subjects.
CONCLUSIONS—Oral amino acids improve cognitive function in response to hypoglycemia and enhance the response of glucagon in nondiabetic and diabetic subjects.
Silicone Tubing is not Necessary after Primary Endoscopic Dacryocystorhinostomy: A Prospective Randomized Study
Authors: Smirnov Grigori , Tuomilehto Henri , Terasvirta Markku , Nuutinen Juhani , Seppa Juha 
Published: April 2008

Background Endoscopic dacryocystorhinostomy (EN-DCR) is an effective procedure when treating saccal and postsaccal obstructions of the nasolacrimal pathway. The benefit of silicone tubing after DCR is still controversial. We conducted a prospective, randomized study to evaluate the necessity of bicanalicular silicone tubes after primary EN-DCR. Methods Forty-six consecutive primary EN-DCR procedures were performed in 42 patients during 2004-2007. The patients were randomized into two study groups according to whether silicone tubing was used or not. Results The overall success rate after primary EN-DCR was 89%: with silicone tubes it was 78%, and without silicone tubes it was 100%. The difference between these two groups was statistically significant (p < 0.049). The follow-up period was 6 months and included three follow-up visits: 1 week, 2 months, and 6 months postoperatively. If inserted, the silicone tubes were removed at the 2-month visit. Conclusion The results of our prospective, randomized study showed that the use of silicone tubes after primary EN-DCR is not necessary.
Allergic Profiles in Unilateral Nasal Polyps of Bilateral Chronic Rhinosinusitis
Authors: Li Jian-Yuan , Fang Sheen-Yie 
Published: April 2008

Background Bilateral chronic rhinosinusitis (CRS), with unilateral nasal polyps (NPs), is a good model for study, being characterized by a similar inflammatory reaction and environment in both nasal cavities of a subject, although NPs exist in only one nasal cavity. It may be feasible to identify specific pathological factors responsible for the disparities by comparing the differences between the nasal cavities. Methods In patients with bilateral CRS, polyp tissue and the middle turbinate tissue on the side of the polyp were examined and compared with contralateral nonpolyp middle turbinate tissue. Tissue and serum-specific immunoglobulin E (sIgE) levels were measured, and eosinophilic infiltration, interleukin (IL)-5 and IL-1-beta were assessed also in the polyp tissue. Results The presence of allergic symptoms correlated well with a positive serum CAP test but poorly with a positive tissue CAP test. There were no obvious differences between tissue sIgE levels on the NP side compared with the nonpolyp side. Tissue eosinophilia was a general characteristic of NPs, whether there was allergy or not. IL-5 and IL-1-beta levels were elevated in NPs, regardless of allergy. There were no differences in the specimens on the nonpolyp side between allergy and nonallergy groups. Conclusion With this model, we have more precise, however, not new results. Localized allergic reaction is not a major factor for the development of a unilateral polyp. Inflammation associated with eosinophilic infiltration and the presence of proinflammatory cytokines, including IL-5 and IL-1-beta, are more important in the pathogenesis of NPs than the allergic reaction.
Th2 Cytokines associated with Chronic Rhinosinusitis with Polyps Down-Regulate the Antimicrobial Immune Function of Human Sinonasal Epithelial Cells
Authors: Ramanathan Murugappan , Lee Won-Kyung , Spannhake Ernst W. , Lane Andrew P. 
Published: April 2008

Background Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a disorder characterized by persistent eosinophilic Th2 inflammation and frequent sinonasal microbial colonization. It has been postulated that an abnormal mucosal immune response underlies disease pathogenesis. The relationship between Th2 inflammatory cytokines and the innate immune function of sinonasal epithelial cells (SNECs) has not been explored. Methods Human SNECs (HSNECs) isolated from control subjects and patients with CRS were assessed for expression of antimicrobial innate immune genes and proinflammatory cytokine genes by real-time polymerase chain reaction, ELISA, and flow cytometry. A model of the Th2 inflammatory environment was created by exposure of primary HSNEC to the Th2 cytokine interleukin (IL)-4 or IL-13 for 36 hours, with subsequent assessment of innate immune gene expression. Results HSNEC obtained from CRSwNP patients displayed decreased expression of multiple antimicrobial innate immune markers, including toll-like receptor 9, human beta-defensin 2, and surfactant protein A. Baseline expression of these genes by normal and CRS HSNEC in culture is significantly down-regulated after incubation with IL-4 or IL-13. Conclusion Expression of multiple innate immune genes by HSNEC is reduced in CRSwNP. One mechanism appears to be a direct effect of the leukocyte-derived Th2 cytokines present in the sinonasal mucosa in CRSwNP. Impaired mucosal innate immunity may contribute to microbial colonization and abnormal immune responses associated with CRSwNP.
Influence of Essential and Fatty Oils on Ciliary Beat Frequency of Human Nasal Epithelial Cells
Authors: Neher Andreas , Gstöttner Michaela , Thaurer Michael , Augustijns Patrick , Reinelt Monika , Schobersberger Wolfgang 
Published: April 2008

Background In alternative and complementary medicine, the use of essential and fatty oils has become more and more popular. In addition to conventional medical therapies, self-medication is showing increasing popularity, using agents with unclear compounds and poorly controlled dosages. Among other disorders, these alternative treatments are used in bronchitis and rhinitis, including some topical applications. Thus, the influence on ciliated epithelia should be evaluated, because a disturbance of the ciliary function can lead to recurrent sinusitis and chronic rhinosinusitis. The aim of this study was to test the influence of fatty and essential oils on the ciliary beat frequency (CBF) of nasal mucosa in vivo. Methods The influence of sesame oil, soy oil, peanut oil, Miglyol 840, thyme oil, lavender oil, eucalyptus oil, and menthol on the ciliary activity of nasal brushings was evaluated by digital high-speed imaging. Results The presence of most fatty oils resulted in an increase in CBF, the effect being highest for peanut oil. Miglyol 840 had no significant influence on CBF. The essential oils were tested at a concentration of 0.2 and 2%. Thyme oil did not affect CBF, whereas the presence of all other essentials oils resulted in an increase in CBF; the effect was higher at 0.2% than at 2%. Conclusion Except thyme oil and Miglyol 840, all tested oils caused an increase in CBF. Interestingly, the 0.2% concentrations of essential oils resulted in stronger effects when compared with the 2% concentrations.
Expression of Mammaglobins A and B in Nasal Polyps is Similar in Patients with and without Allergic Rhinitis
Authors: Chusakul Supinda , Phannaso Chuntima , Tongkobpetch Siraprapa , Aeumjaturapat Songklot , Poovorawan Yong , Suphapeetiporn Kanya , Shotelersuk Vorasuk 
Published: April 2008

Background The causes of nasal polyposis remain unclear. Mammaglobins have been implicated in its pathogenesis. However, their association with the occurrence of nasal polyps in the presence of allergic rhinitis (AR) has not been explored. The aim of this study was to compare the expression levels of mammaglobins A and B with the nasal polyps of patients with and without AR. Methods Thirty-one patients with bilateral nasal polyposis underwent skin-prick tests to specific aeroallergens. Nasal polyp tissues were obtained from all patients and divided into two groups as nasal polyps with and without AR depending on clinical history and the skin-prick test results. All polyp tissues were analyzed for the levels of mammaglobin A and mammaglobin B by using real-time quantitative polymerase chain reaction technique. Results Of the 16 samples from patients having nasal polyps with AR, only 1 sample expressed a detectable level of mammaglobin A (1/16). There was no detectable expression of mammaglobin A in tissues from the group of nasal polyps without AR (0/15). Expression of mammaglobin B was detected in all nasal polyp tissues from both groups. The expression of mammaglobin B was not significantly different between nasal polyps with AR (median, 25th-75th percentiles; 0.023, 0.013-0.046) and nasal polyps without AR (0.032, 0.007-0.16). Conclusion Expression levels of mammaglobins A and B in nasal polyps are not different between patients with and without AR. Our findings suggest that mammaglobins’ implication in the pathogenesis of nasal polyps is independent of an underlying AR.
Expression of Survivin and Enhanced Polypogenesis in Nasal Polyps
Authors: Qiu Zhe-Fu , Han De-Min , Zhang Luo , Zhang Wei , Fan Er-Zhong , Cui Shun-Jiu , Huang Qian , Wang Xiang-Dong 
Published: April 2008

Background The pathogenesis of nasal polyps still is not clear. This disease is believed to be inflammation related. Previous research has indicated that apoptosis in inflammatory cells is an important factor in the resolution of inflammation. Survivin is regarded as a novel member of the group of inhibitors of apoptosis proteins. It is overexpressed in a number of tumor types. The objective of this study was to investigate the expression of the survivin gene in human nasal polyps. Methods We investigated the expression of survivin in nasal polyps of adult patients with chronic rhinosinusitis. Specimens of nasal polyps were harvested during endonasal sinus surgery (n = 22), and the normal mucosa surrounding the nasal polyp tissues or inferior turbinate tissues served as control (n = 7). Immunohistochemical staining, reverse transcription polymerase chain reaction (RT-PCR), and Western blotting were performed for detecting the expression of survivin in the nasal polyps. Results This study has clearly shown that immunoreactivity of survivin significantly increased in the nasal polyp compared with nasal mucosa specimens surrounding nasal polyps (p < 0.001). The higher expression of survivin Western blotting and RT-PCR also was observed in the nasal polyp but not in normal nasal mucosa. Conclusion With a markedly increased expression of survivin in nasal polyps at both the mRNA and the protein levels, we believe the elevated expression of survivin might play an important role of the development in nasal polyps.
Orbital and Cranial Nerve Presentations and Sequelae are Hallmarks of Invasive Fungal Sinusitis caused by Mucor in Contrast to Aspergillus
Authors: Ingley Avani P. , Parikh Shatul L. , DelGaudio John M. 
Published: April 2008

Background Acute fulminant invasive fungal sinusitis (IFS) is a rapidly progressing, destructive process almost exclusively affecting immunocompromised patients. Outcome differences have been found in patients with Mucor and Aspergillus. We performed this study to compare the presenting symptoms and long-term morbidity with IFS caused by Mucor versus Aspergillus species. Methods Retrospective chart review was performed of 48 patients with 49 cases of acute fulminant IFS over a 19-year period. Presenting symptoms and long-term morbidity related to the orbits and cranial nerves were evaluated. Results Mucor was found in 22 cases and Aspergillus was found in 27 cases. Orbital (proptosis, periorbital edema, and ophthalmoplegia) and cranial nerve symptoms were seen at presentation more often in Mucor (6 [27%] and 9 [41%]) than in Aspergillus patients (3 [11%] and 7 [26%]; p = 0.079). Long-term orbital and cranial nerve sequelae occurred in 16 (72%) Mucor cases and 10 (37%) Aspergillus cases (p = 0.0210). The IFS-related mortality was 32% (7) in the Mucor group and 11% (3) in the Aspergillus group (p = 0.089). Conclusion Patients with acute fulminant IFS present with similar sinus symptoms; however, there is a trend toward a greater prevalence of orbital and neurological symptoms in patients with Mucor versus Aspergillus. Long-term orbital and neurological morbidity is more prevalent in patients with Mucor compared with Aspergillus. These data suggest that the presence of orbital and neurological symptoms at presentation warrants more aggressive surgical intervention because of the likelihood of Mucor.
The Roles and Limitations of Computed Tomography in the Preoperative Assessment of Sinonasal Inverted Papillomas
Authors: Sham C.L. , King Ann D. , van Hasselt Andrew , Tong Michael C.F. 
Published: April 2008

Background Preoperative radiological assessment of sinonasal inverted papilloma (SNIP) is important in the planning of surgical treatment. This study investigates the roles and limitations of preoperative plain computed tomography (CT) scan in the preoperative assessment of SNIP. Methods Plain CT scans from 30 patients with SNIP were reviewed retrospectively by a radiologist who had no prior knowledge of the final surgical findings. Disease at each sinus was judged by the CT findings of opacity and additional signs. The overall disease was staged according to the staging system proposed by Krouse. All of the findings were compared with the final disease extent and staging confirmed by intraoperative and histological findings. Results Using opacity with additional signs for diagnosis, the range of accuracy of CT diagnosis for each sinus involvement was 83-97%. Staging by plain CT was concordant with postoperative staging in 80% of patients. Among the additional signs, focal hyperostosis or “bony strut” had the highest positive predictive value (100%) of tumor origin. Conclusion Focal hyperostosis or bony strut is the most important CT sign predicting the origin of tumor. Although using multiple CT diagnostic signs provides a reasonable assessment of tumor origin and extent, accurate tumor mapping was still impossible because of inadequate differentiation of tumor from inflammatory pathologies. This drawback may be overcome by a complementary MRI scan. Since preoperative CT staging was inaccurate in 20% of cases, surgical planning should be flexible to provide for the need of the intraoperative findings.
Effect of Postural Change on Nasal Airway and Autonomic Nervous System Established by Rhinomanometry and Heart Rate Variability Analysis
Authors: Ko Jen-Hung , Kuo Terry B.J. , Lee Guo-She 
Published: April 2008

Background Clinically, nasal obstruction is experienced frequently in the supine position, and the nasal autonomic nervous system (ANS) may be involved in the mechanism. The central ANS functions at maintaining cardiovascular hemodynamics. However, during postural change, the corresponding changes of the central ANS may simultaneously change the nasal airway as well. In this study, the relationships between nasal ANS and central ANS were explored using rhinomanometry (RMM) and heart rate variability (HRV) analysis between postural changes. Methods Twelve healthy volunteers aged between 19 and 39 years and without a history of allergic rhinitis or significant nasal anatomic obstruction were enrolled for the study. The nasal airway was measured using RMM in a sitting position and then in a supine position; the electrocardiography was simultaneously recorded. Results In supine position, the total nasal airflow significantly decreased and the airway resistance significantly increased (p < 0.05, Wilcoxon signed-rank test). The ratio of low frequency power to high frequency (HF) power of HRV that represents sympathetic modulation significantly decreased in the supine position (p < 0.05, Wilcoxon signed-rank test). However, the HF that represents parasympathetic activity did not show significant change with postural change. The correlations of heartbeat interval with total inspiratory airflow and total inspiratory resistance were significant also (p < 0.01, Pearson's correlation). Conclusion The central ANS activities significantly correlated with changes to the nasal airway during postural change. The central ANS, especially the sympathetic nervous system, may play a role in controlling nasal airway during postural change.
A Randomized Controlled Pilot Study of Epsilon-Aminocaproic Acid as a Topical Hemostatic Agent for Postoperative Bleeding in the sheep Model of Chronic Sinusitis
Authors: Thomas Devika C. , Wormald Peter-John 
Published: April 2008

Background Significant bleeding with blood clot formation in the postoperative period may predispose to the formation of postoperative adhesions. A topical hemostatic agent would potentially improve postoperative comfort and lessen adhesion formation. This pilot study was performed to evaluate the effects of a novel topical hemostatic agent AMICAR (e-aminocaproic acid; Xanodyne Pharmacal, Inc., Florence, KY) on postoperative bleeding after endoscopic sinus surgery (ESS). Methods In a prospective randomized controlled pilot study full thickness mucosal injuries were created on the lateral nasal wall, ethmoturbinal and the maxillary ostium on both sides of 10 sheep. Eosinophilic chronic sinusitis was confirmed both by endoscopy and by biopsy before full thickness injuries. The topical hemostatic agent (AMICAR) was sprayed onto a randomly selected side with or without mucoadhesive methyl cellulose (5 sheep in each group). The control side received a spray of saline of equal volume. The degree of bleeding in the surgical field was graded using a visual analog scale until total hemostasis was achieved. The grades at 2-minute intervals as well as the time to achieve total hemostasis were recorded. Results Eosinophilia of the epithelium did not correlate with the severity of bleeding (p < 0.05). There was a statistically significant reduction in the grade of bleeding in the lateral nasal wall both superior and inferior to the middle turbinate attachment when AMICAR alone was used compared with normal saline (p = 0.004 and p = 0.003, respectively) but when AMICAR was used in combination with methyl cellulose this significance was lost (p = 0.076 and p = 0.502). Conclusion AMICAR may be considered for use either during or after sinus surgery to reduce bleeding.