bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Lateral Arm Free Flap in Oral and Maxillofacial Reconstruction following Tumor Surgery
Authors: Song Xiao-meng , Yuan Ye , Tao Zhen-jiang , Wu He-ming , Yuan Hua , Wu Yu-nong
Published: August 2007

Objective: To describe the application of lateral arm free flap (LAFF) in reconstruction of defects in the oral and maxillofacial regions following ablative oncological surgery. Subjects and Methods: The study included 16 patients (13 male, 3 female, mean age 56, range 35–69 years). Sixteen LAFF were harvested to reconstruct defects caused by the dissection of malignant tumors of the oral and maxillofacial regions. The tumor was squamous cell carcinoma of the tongue (6 cases), floor of the mouth (4), retromolar area (3), inner cheek (2), and lower gingival (1). Flap sizes ranging from 5 × 7 to 6 × 9 cm were harvested using a sterile tourniquet for bloodless technique. The anastomoses were carried out using a magnifier or microscope. All donor defects were closed primarily. Results: Fourteen flaps healed without venous insufficiency. One flap, in a female patient, survived with mild local microcirculatory obstruction but that of another female patient developed necrosis. There was no significant complication at the donor sites. The advantages of this flap include anatomically reliable vascular supply, accessible donor site, and the aesthetic quality of donor tissue is good. Compared with the radial artery, the posterior radial collateral artery is a nonessential vessel of the arm. The disadvantages are the relatively smaller vessel size for anastomosis and thicker subcutaneous tissue. Conclusions: For the repair of moderate-sized defects of the maxillofacial area, especially in male patients, the LAFF can be recommended.
Occupationally Related Outbreak of Chickenpox in an Intensive Care Unit
Authors: Aly Nasser Yehia A. , Al Obaid Ina’am , Al-Qulooshi Noura , Zahed Zahida
Published: August 2007

Objective: To report occupationally related outbreak of chickenpox in intensive care unit (ICU). Case Presentation and Intervention: The index patient was a 4-year-old child who presented with a 3-day history of fever and rash and was clinically diagnosed as chickenpox encephalitis. She was admitted to an isolation room in ICU, kept on oxygen mask and given intravenous fluids, anticonvulsant, antipyretic and acyclovir. Twelve hours later, the patient was transferred to Infectious Diseases Hospital. Secondary cases were three unvaccinated ICU staff nurses who developed chickenpox 16–21 days following exposure. They were also transferred to Infectious Diseases Hospital. The affected nurses were interviewed and filled out a questionnaire. Individual immune status was verified by reviewing previous varicella zoster-IgG screening data for all ICU staff. The chickenpox case was defined according to the CDC case classification. All were treated with no complications. Conclusion: This report shows that adherence to isolation precautions, exclusion of susceptible staff from attending the affected patient, education, pre-employment anti-VZV-IgG screening and vaccine coverage of staff could have prevented the occurrence of this outbreak.
Non-Cardiovascular Mortality, Low-Density Lipoprotein Cholesterol and Statins: A Meta-Regression Analysis
Authors: Razzolini Renato , Tarantini Giuseppe , Ossena Giovanni , Favaretto Enrico , Bilato Claudio , Manzato Enzo , Dalla-Volta Sergio , Iliceto Sabino
Published: August 2007

Background: As of today, the effect of statins on non-cardiovascular mortality is still being debated. Single studies have not been able to provide definite answers. We performed a meta-regression analysis on randomized statin trials in order to provide evidence that non-cardiovascular mortality is related to statin treatment and low-density lipoprotein (LDL) cholesterol plasma level. Methods: We selected 29 randomized controlled trials of statins versus placebo, a total of 90,480 patients, with a follow-up of >12 months. Baseline and follow-up LDL levels and all-cause, cardiovascular and non-cardiovascular mortality were recorded. Weighted linear regression analysis was carried out separately for placebo and treatment groups. Results: LDL level was inversely related to overall mortality (p = 0.0105) and non-cardiovascular mortality (p = 0.0171) in the treatment group. By contrast, in the placebo group only non-cardiovascular mortality was inversely correlated to LDL (p = 0.0032). The regression lines have similar slopes and run almost parallel to each other, with the treatment line lying below the placebo line. To identify the threshold of risk for starting statin therapy, we analysed the relationship between baseline cardiovascular risk and overall mortality in the two groups. Both correlations are highly significant and regression lines intersect at a risk of 0.29% per year. This implies that the effects of statins are favourable when the baseline cardiovascular risk exceeds approximately 3% in 10 years. Conclusions: A trend of increased non-cardiovascular mortality with decreased LDL exists both in placebo and treatment groups. However, at each given LDL cholesterol level, non-cardiovascular mortality is lower in treated patients. Therefore, statin therapy may improve the biological impact of LDL on non-cardiovascular mortality.
Isolated Cardiac Sarcoidosis Associated with the Expression of a Splice Variant Coding for a Truncated BTNL2 Protein
Authors: Meyer Thomas , Lauschke Jörg , Ruppert Volker , Richter Anette , Pankuweit Sabine , Maisch Bernhard
Published: August 2007

A 33-year-old woman presented with clinical signs of heart failure and previously diagnosed complete atrioventricular block. DNA sequencing revealed a homozygous point mutation in exon 5 of the btnl2 gene coding for a truncated protein which lacks the membrane-anchoring motif. This single nucleotide polymorphism is known to be a risk factor for sarcoidosis. Indeed, endomyocardial biopsy demonstrated multiple nonnecrotizing granulomas composed of epitheloid cells and moderate numbers of multinucleated giant cells. Because no other organs were affected, isolated cardiac sarcoidosis was diagnosed and treated with corticosteroids. Thus, detection of the disease-associated btln2 allele may help to identify patients with sarcoidosis as the underlying cause of heart failure.
Neuropsychiatric Symptoms Are Associated with Progression from Mild Cognitive Impairment to Alzheimer’s Disease
Authors: Teng Edmond , Lu Po H. , Cummings Jeffrey L.
Published: August 2007

Background: Neuropsychiatric disturbances are common in mild cognitive impairment (MCI). Depression and apathy may identify a subset of MCI subjects at higher risk of progression to Alzheimer’s disease (AD). However, it remains uncertain whether a broader spectrum of psychopathology is associated with progression to AD. Methods: Fifty-one MCI subjects were assessed for neuropsychiatric symptoms using the Neuropsychiatric Inventory. Subjects were followed for an average of 2 years. Twelve subjects (23.5%) progressed from MCI to possible/probable AD and 39 subjects (76.5%) remained stable or improved. Baseline Neuropsychiatric Inventory indices were compared between groups. Results: Subjects progressing to AD had a significantly higher prevalence of psychopathology than subjects who remained stable or improved (100 vs. 59%). Depression (67 vs. 31%) and apathy (50 vs. 18%) were more common in subjects who were later diagnosed with AD. After statistical adjustments for other baseline demographic variables, these specific symptoms were less robust predictors of progression to AD than the presence of any psychopathology. Conclusions: These findings suggest that neuropsychiatric symptoms in MCI are a predictor of progression to AD. Depression and apathy appear to be most useful for identifying MCI subjects at highest risk of developing dementia.
The Combined Effect of Age, Education, and Stroke on Dementia and Cognitive Impairment No Dementia in the Elderly
Authors: De Ronchi Diana , Palmer Katie , Pioggiosi Philippe , Atti Anna Rita , Berardi Domenico , Ferrari Barbara , Dalmonte Edoardo , Fratiglioni Laura
Published: August 2007

Background: This study aims to detect the impact of stroke on the occurrence of dementia and cognitive impairment/no dementia (CIND) in different age, sex, and education groups. Methods: Persons with dementia (DSM-III-R) or CIND were identified by a two-phase study design among 7,930 persons from the population-based Faenza Community Aging Study. Results: Subjects with a history of stroke had increased risk of both dementia [risk ratio (RR) = 3.7; 95% confidence interval (CI) = 3.1–4.4] and CIND (RR = 1.7, 95% CI = 1.4–2.2). These associations were stronger in the younger-old (61–74 years) than in the older-old (75+ years), and among higher-educated (4+ years) than lower-educated (0–3 years of schooling) persons. Dementia and CIND prevalence among stroke subjects was similar to the prevalence detected among subjects 10 years older but without a history of stroke. In stroke subjects, dementia prevalence became higher than CIND prevalence 10 years earlier than in non-stroke subjects. A combined effect for dementia due to a history of stroke, increasing age, and decreasing years of schooling was detected. Conclusions: Stroke is a strong risk factor for dementia among younger-old and higher-educated subjects; in the presence of a stroke, dementia onset might occur about 10 years earlier, possibly by accelerating the progression from CIND to dementia.
Effect of Maternal Administration of Betamethasone on Peripheral Arterial Development in Fetal Rabbit Lungs
Authors: Roubliova Xenia I. , Van der Biest AnneMarie , Vaast Pascal , Lu HuiQi , Jani Jacques , Lewi Paul J. , Verbeken Eric K. , Tibboel Dick , Deprest Jan A.
Published: August 2007

Objectives: Glucocorticoids promote lung maturation and reduce the incidence of respiratory distress syndrome in premature newborns. We hypothesized that betamethasone (BM), which is known to induce thinning of the alveolar walls, would also thin the arterial media and adventitia of intra-parenchymatic vessels in developing rabbit lungs. Study Design: 112 fetuses from 21 time-mated, pregnant, giant white rabbits received maternal injections of BM at either 0.05 or 0.1 mg/kg/day on days 25–26 of gestational age. Controls received either saline (10 does, 56 fetuses) or no injection (10 does, 59 fetuses). Fetuses were harvested from day 27 onwards until term (day 31). 44 additional fetuses (8 does) were harvested between days 23 and 26. Endpoints were wet lung-to-body weight ratio, vascular morphometric indices and immunohistochemistry staining for α-smooth muscle actin, Flk-1, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). ANOVA (Tukey’s test) and independent t test (p < 0.05) were used for comparison between BM and saline groups. Results: Maternal BM injected on days 25–26 to pregnant rabbits induced a significant decrease in fetal body and lung weight and the lung-to-body weight ratio in the preterm pups shortly after injection. BM led to a dose-dependent thinning of the arterial media and adventitia (pulmonary arteries with an external diameter (ED) of <100 µm), to an increase in the percentage of non-muscularized peripheral vessels (ED <60 µm), in eNOS and VEGF immunoreactivity of the endothelial and smooth muscle cells in the pulmonary vessels and to an increase in Flk-1-positive pulmonary epithelial cell density. Conclusions: Maternal administration of BM caused thinning of the arterial wall of pulmonary vessels (ED <100 µm) and a decrease in muscularization in peripheral vessels (ED <60 µm). This coincided with increased expression of Flk-1 in the endothelium and smooth muscle cells of the pulmonary arteries. All the effects studied were dose-dependent.
Hepatitis C Virus F Protein Up-Regulates c-myc and Down-Regulates p53 in Human Hepatoma HepG2 Cells
Authors: Wu Wen-bin , Shao Sheng-wen , Zhao Lan-juan , Luan Jie , Cao Jie , Gao Jun , Zhu Shi-ying , Qi Zhong-tian
Published: August 2007

Objectives: Hepatitis C virus (HCV) F protein is a newly identified protein encoded by an alternative open reading frame that +1 overlaps core-encoding gene. It has been found that regulation of c-myc and p53 genes by HCV core protein is involved in liver cancer genesis. We wondered whether HCV F protein exerts similar or adverse regulatory effects on the transcription of c-myc and p53 genes. Methods: HCV F gene-containing, plasmid pcDNA3.1-F and HCV core gene-containing pcDNA3.1-C were constructed and transiently transfected into HepG2 cells. Real-time quantitative PCR or Western blotting was used to determine the changes at transcription or translation levels of c-myc and p53 genes. Results: The transcription level of c-myc was much higher in pcDNA3.1-F transfected cells than those without plasmid transfected. Whereas the level of p53 transcription in pcDNA3.1-F transfected cells was lower than those in the parental cells. Moreover, levels of c-myc expression were up-regulated and those of p53 expression were down-regulated by HCV F protein. Conclusions: HCV F protein is of regulatory properties in cellular oncogene c-myc and anti-oncogene p53, which may be implicated in the formation of hepatocellular carcinoma.
Evidence of Vertical Transmission of Dengue Virus in Two Endemic Localities in the State of Oaxaca, Mexico
Authors: Günther Jeannette , Martínez-Muñoz Jorge Pascual , Pérez-Ishiwara David Guillermo , Salas-Benito Juan
Published: August 2007

Background: Dengue virus is spread in tropical areas of the world and is the causative agent of dengue fever and dengue hemorrhagic fever. It is horizontally transmitted to humans by infected Aedes mosquitoes, but it is also able to be vertically or transovarially transmitted to insect progeny. Objective: In this work, we analyzed the vertical transmission of dengue virus in Aedes aegypti mosquitoes collected in two endemic localities in the state of Oaxaca, Mexico. Methods: The collected larvae were grown in the laboratory and transovarial transmission of dengue virus, either in larvae or newly emerged mosquitoes, was investigated using a semi-nested reverse transcription-polymerase chain reaction method. Results: Although the presence of dengue virus in larvae could not be demonstrated, the viral genome was amplified in 4 out of 43 pools of in-cage born mosquitoes: DEN 2, 3 and 4 serotypes were detected in 2 pools from Tuxtepec and two from Juchitán. Conclusion: The results presented here strongly suggest that dengue virus can be vertically transmitted in mosquitoes from Oaxaca, but more studies will be necessary to analyze the epidemiological impact of this mechanism of transmission.
Stress-Induced Downregulation of Macrophage Phagocytic Function Is Attenuated by Exercise Training in Rats
Authors: Leandro Carol Góis , de Lima Thais Martins , Alba-Loureiro Tatiana Carolina , do Nascimento Elizabeth , Manhães de Castro Raul , de Castro Célia M.M.B. , Pithon-Curi Tania Cristina , Curi Rui
Published: August 2007

Background/Aims: Acute restraint stress may induce impaired macrophage phagocytic function. Moderate physical training is associated with beneficial effects on immunological functions. We investigated the effects of moderate physical training on phagocytic function of alveolar macrophages in rats submitted to acute restraint stress. Methods: Thirty male Wistar rats weighing 210–226 g were randomly divided into 4 groups: nontrained rats (n = 7), nontrained rats submitted to stress (n = 8), trained rats (n = 7) and trained rats submitted to stress (n = 8). Trained rats were submitted to a program of moderate running training over a period of 8 weeks. Rats subjected to restraint stress were kept immobilized in glass cylinders (8 cm in diameter and 24 cm long) during 60 min. Phagocytosis capacity of macrophages was evaluated by either Escherichia coli orzymosan stimuli. Results: Restraint stress induced a decrease in phagocytosis of E. coli and zymosan particle stimulation by macrophages. Neither of these alterations was observed in trained animals submitted to acute restraint stress. Conclusions: Our data confirm that acute restraint stress is associated with impaired function of macrophages. Moreover, moderate physical training attenuates the effects of acute stress by a mechanism that involves an increase in tolerance of macrophages.
Elevated Inflammation Markers in Pheochromocytoma Compared to Other Forms of Hypertension
Authors: Zelinka Tomáš , Petrák Ondřej , Štrauch Branislav , Holaj Robert , Kvasnička Jan , Mazoch Jiří , Pacák Karel , Widimský, Jr. Jiří
Published: August 2007

Objective: To investigate the effect of long-term catecholamine excess in pheochromocytoma on leukocyte and platelet count and on proteins of acute-phase response. Methods: Fifteen subjects with pheochromocytoma, 16 with primary aldosteronism, 18 with essential hypertension and 17 healthy controls were studied. Sixteen subjects with pheochromocytoma were investigated after tumor removal. Leukocyte, neutrophil and platelet count, as well as C-reactive protein were measured in all subjects, while fibrinogen, α1-antitrypsin, α2-macroglobulin, orosomucoid, transferrin and prealbumin were only measured in subjects with pheochromocytoma, primary aldosteronism and essential hypertension. Results: Subjects with pheochromocytoma showed significantly higher leukocyte [7.5 ± 0.9 109/l, p < 0.001 vs. primary aldosteronism (5.4 ± 0.9 109/l) and healthy controls (5 ± 0.9 109/l), p = 0.04 vs. essential hypertension (6.3 ± 1.6 109/l)], neutrophil (p < 0.001 vs. primary aldosteronism and healthy subjects) and platelet counts (p < 0.001 vs. primary aldosteronism; p = 0.01 vs. essential hypertension) compared to the other groups of subjects. Similar results were obtained for positive proteins of acute-phase response in subjects with pheochromocytoma [C-reactive protein: 0.62 ± 0.52 mg/dl, p < 0.001 vs. healthy subjects (0.08 ± 0.08 mg/dl), p = 0.001 vs. primary aldosteronism (0.17 ± 0.19 mg/dl), p = 0.04 vs. essential hypertension (0.31 ± 0.26 mg/dl); fibrinogen: p = 0.02 vs. primary aldosteronism; orosomucoid: p = 0.005 vs. primary aldosteronism; α2-macroglobulin: p = 0.009 vs. primary aldosteronism]. No significant differences were found in plasma levels of α1-antitrypsin, transferrin and prealbumin. Tumor removal led to a significant decrease in leukocyte (p = 0.004), neutrophil (p = 0.007) and platelet count (p = 0.003) and also to a significant decrease in acute-phase proteins (C-reactive protein: p = 0.03, fibrinogen: p = 0.008, α1-antitrypsin: p = 0.003, orosomucoid: p = 0.04). Conclusions: Chronic catecholamine excess in pheochromocytoma is accompanied by an increase in inflammation markers which was reversed by the tumor removal.
Gene Expression Profiles of Adult Peripheral and Cord Blood Mononuclear Cells Altered by Lipopolysaccharide
Authors: Koch Lutz , Linderkamp Otwin , Ittrich Carina , Benner Axel , Poeschl Johannes
Published: August 2007

Background: Neonatal Gram-negative sepsis is often characterized by a fulminant clinical course, compared to adults, resulting in higher morbidity and mortality. Genome-wide gene expression analysis can provide insights into the molecular alterations in sepsis. Objectives: To evaluate in vitro activation of the neonatal and adult immune system, gene expression patterns were compared in mononuclear cells from cord (CBMNC) and adult peripheral blood (APBMNC). Methods: To better understand the influence of early molecular signals on the effects of sepsis, Affymetrix gene profiling (8,475 genes) was done on RNA isolated from CBMNC and APBMNC without and after incubation with 100 ng/ml lipopolysaccharide (LPS). Results: We demonstrated significant alterations in the expression of 108 CBMNC and APBMNC genes compared with basal levels, 188 significant changes in CBMNC and 97 in APBMNC, including cytokines, chemokines and immunoregulatory genes. Furthermore, we found 5 genes showing a significant interaction effect between cell type and LPS stimulation, including tumor necrosis factor receptor superfamily, member 6 (FAS), absent in melanoma 2, malic enzyme 1, hemoglobin Ε 1, and trans-prenyltransferase. Conclusions: These results provide further support for a marked difference in the pathogenesis of neonatal and adult sepsis and may stimulate additional studies to investigate some of the altered genes as potential new targets for diagnostic tools and therapeutic strategies.
Transcutaneous Bilirubin Measurement: Evaluation of Bilitest™
Authors: Bertini Giovanna , Pratesi Simone , Cosenza Elena , Dani Carlo
Published: August 2007

Objective: The early discharge of neonates from hospitals makes transcutaneous measurement of total serum bilirubin concentration a useful tool to monitor neonatal jaundice. The objective of this study was to evaluate the Bilitest BB 77™ (Bertocchi SRL Elettromedicali, Cremona, Italy), a new device for noninvasive transcutaneous total bilirubin measurement. Methods: We studied 241 newborn infants ≧32 weeks of gestation admitted to the Neonatal Nursery of Careggi University Hospital, Florence. These infants had total serum bilirubin (TSB) levels measured by a standard laboratory test (group B = 198) as part of their normal care, and transcutaneous bilirubin (TcB) levels were obtained within 10 min after heel pricking. Results: There was a good correlation between TSB and TcB values. The linear regression plot showed a general underestimation of Bilitest BB 77 measurement compared to standard laboratory test; the negative difference between Bilitest BB 77 values and TSB increased at higher bilirubin levels, as confirmed by the Bland-Altman error plot. To visualize the accuracy of the Bilitest BB 77 measurements, ROC curves plot sensitivity versus specificity and the maximum range of difference between Bilitest BB 77 and TSB were considered. Pearson correlation analysis demonstrated that Bilitest BB 77 accuracy was independent of gestational and postnatal age of newborns. Conclusion: We conclude that the Bilitest BB 77, a new device for bilirubin transcutaneous measurement, shows a good correlation with standard laboratory method and has the merit to be quite inexpensive and does not need calibration with consumable or disposable parts. However, because TcB measurements with Bilitest BB 77 underestimated STB levels particularly at STB ≧12 mg/dl, serum bilirubin measurements are still required when treatment with phototherapy or exchange transfusion is being considered.
Simultaneous and Sequential Bilateral Sudden Sensorineural Hearing Loss: Are They Different from Unilateral Sudden Sensorineural Hearing Loss?
Authors: Xenellis John , Nikolopoulos Thomas P. , Stavroulaki Pelagia , Marangoudakis Pavlos , Androulakis Michael , Tsangaroulakis Michael , Ferekidis Eleftherios
Published: August 2007

Aim: To compare bilateral (BSSHL) with unilateral (USSHL) sudden sensorineural hearing loss. Methods and Subjects: Two hundred and thirty-two patients with USSHL, 11 with simultaneous BSSHL and 7 with sequential BSSHL, who were older than 15 years had onset of hearing loss <30 days, no head injuries or history of acoustic trauma. All patients received the same treatment (prednisolone). Results: Hearing loss was more severe in simultaneous BSSHL in comparison to sequential BSSHL (p = 0.01) or USSHL (p = 0.03). Autoimmune diseases were far more common in simultaneous BSSHL (36% of patients) than USSHL. Positive antinuclear antibody was found in half of BSSHL patients and in only 8% of unilateral cases (p = 0.01). The frequency of hearing improvement was much lower in simultaneous BSSHL than in USSHL (p = 0.001). Complete or partial improvement was noted in 74% of unilateral cases versus 27% in simultaneous bilateral cases. Patients with sequential BSSHL improved in a similar way to unilateral cases. Conclusions: Simultaneous BSSHL, sequential BSSHL and USSHL may have a completely different profile and should not be managed as one disease. Hearing loss, underlying autoimmune diseases, antinuclear antibodies, and improvement/recovery of hearing loss vary in a degree that implies different pathophysiology and prognosis.
Complication of Laparoscopic Detorsion of Adnexal Mass
Authors: Aharoni A. , Leibovitz Z. , Levitan Z. , Degani S. , Ohel G.
Published: August 2007

Detorsion of an ischemic adnexal mass has recently been advocated for most cases of twisted adnexa. Usually, the affected ovary regains some or all of its vitality and function. However, when the ovary is completely necrotic, it may form an abscess if it contains tissue components that cannot be eliminated by the peritoneal immune system. We report a case of pelvic abscess formation in a detorsed ovary that previously contained an unsuspected dermoid cyst. We call for an extensive inspection of the detorsed ovary before ending the laparoscopic operation, and if it remains necrotic and is suspected of containing a dermoid cyst, it should be removed promptly.
Clinical Aspects and Molecular Analysis of Chinese Patients with Wiskott-Aldrich Syndrome in Taiwan
Authors: Lee Wen-I , Yang Chang-Yo , Jaing Tang-Her , Huang Jing-Long , Chien Yin-Hsiu , Chang Kuei-Wen
Published: August 2007

Background: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency, characterized by microthrombocytopenia, eczema and recurrent infections. More than 441 patient mutations have been described all over the world, mainly based on Caucasian and Japanese people. There have been few reported cases involving Chinese WAS patients. Objective: We investigated Chinese WAS patients in Taiwan since 1980. Methods: All WAS patients met the diagnosis criteria. Clinical manifestations, immunological functions, gene sequencing and the WAS protein (WASP) expression were analyzed. Results: Eleven male Chinese WAS patients were enrolled, presenting as classic WAS phenotype, correlative to the expression level of WASP and the severity of infections. Seven patients had autoimmune disorders, encompassing autoimmune hemolysis in 4, lymphoproliferative disorders in 2 and ulcerative colitis in 1 patient. As well as prophylactic monthly intravenous immunoglobulin infusion, splenectomy was performed on 2 patients. Five patients received hematopoietic stem cell transplantation. The causes of mortality were mass bleeding, sepsis and Epstein Barr virus-associated lymphoproliferative disorders in 3 nontransplant patients and acute graft failure and cytomegalovirus pneumonitis in 2 transplant patients. Nine patients received genetic analysis and revealed 4 unique mutations. None had the X-linked thrombocytopenia phenotype. Conclusions: All of the recognized Chinese WAS patients had the classic phenotype. Most mutations involved exon 1 of the WASP gene and none had the X-linked thrombocytopenia phenotype. This may be attributable to genetic variation, although selection bias may exist.
Proinflammatory Impact of Staphylococcus epidermidis on the Nasal Epithelium Quantified by IL-8 and GRO-α Responses in Primary Human Nasal Epithelial Cells
Authors: Sachse F. , von Eiff C. , Becker K. , Steinhoff M. , Rudack C.
Published: August 2007

Background: Bacterial etiology of chronic rhinosinusitis (CRS) still remains controversial. Whereas Staphylococcus aureus enterotoxins have been detected in CRS, the impact of Staphylococcus epidermidis, a major commensal inhabitant of the nose, has not been studied. Among others, serine and cysteine proteases have been identified as factors of virulence in S. epidermidis. Methods:S. epidermidis was examined in tissue biopsies of 30 CRS patients (16 with nasal polyposis) using standard procedures. Primary human nasal epithelial cells from inferior nasal turbinates (HNECs), from nasal polyps (NPECs) and A549 airway epithelial cells were stimulated with S. epidermidis supernatants DSM20044 or ATCC35984 and the IL-8 and GRO-α response was quanti- fied by ELISA. Protease-triggered chemokine responses and involvement of NF-ĸB were investigated by addition of protease or NF-ĸB inhibitors. Activation of NF-ĸB was demonstrated by quantitative DNA binding assay. Results:S. epidermidis was the most frequently isolated bacteria in the majority of CRS patients. HNECs and NPECs revealed no different IL-6 and IL-8 synthesis following stimulation with DSM20044 or ATCC35984. Stimulation of HNECs and A549 cells with S. epidermidis supernatants resulted in increased IL-8 and GRO-α expression which could be suppressed by the serine protease inhibitor AEBSF and the NF-ĸB inhibitor BAY 11 but not by the cysteine protease inhibitor E64. Results obtained for A549 cells were similar to HNECs. Conclusion:S. epidermidis was present in the majority of CRS specimens. Proinflammatory impact of S. epidermidis supernatants on nasal epithelial cells was demonstrated by serine protease-triggered and NF-ĸB-dependent chemokine responses.
House Dust and Storage Mite Extracts Influence Skin Keratinocyte and Fibroblast Function
Authors: Arlian Larry G. , Morgan Marjorie S. , Peterson Kevin T.
Published: August 2007

Background: The bodies of allergy-causing dust and storage mites likely contain many bioreactive molecules, including some that are allergenic. These molecules may penetrate the epidermis and dermis of the skin. However, little is known about the effects that most of the molecules from mites have on the function of cells in the skin, the overall inflammatory and immune reactions and the manifestation of allergic disease.The purpose of this research was to determine the response of cultured skin cells (keratinocytes and fibroblasts) to extracts of house dust and storage mites. Methods: Normal human epidermal keratinocytes and dermal fibroblasts were cultured with varying doses of extracts of the storage mites Acarus siro, Chortoglyphus arcuatus or Lepidoglyphus destructor or of the house dust mites Dermatophagoides farinae, D. pteronyssinus or Euroglyphus maynei in the absence or presence of lipopolysaccharide. Culture supernatants were collected 24 h later and assayed for the presence of various chemokines and cytokines. Results: Keratinocytes constitutively secreted interleukin (IL)-1 receptor antagonist/IL-1F3, growth-related oncogene α and transforming growth factor α, and these secretions were modulated by extracts of 1 or more of the mites tested. Mite extracts also modulated the production of IL-6, IL-8, monocyte chemoattractant protein 1, macrophage colony-stimulating factor and vascular endothelial growth factor from fibroblasts. Conclusions: The effects that mite extracts exerted on both keratinocytes and fibroblasts varied among the house dust mite species, among the storage mite species and between the house dust and storage mites. This study showed that extracts of mites contain substances that modulate the production of proinflammatory cytokines and chemokines secreted by normal human epidermal keratinocytes and dermal fibroblasts, and therefore may influence the course of pathophysiology in the skin in atopic dermatitis.
Association Analysis of Tyrosine Kinase FYN Gene Polymorphisms in Asthmatic Children
Authors: Szczepankiewicz Aleksandra , Bręborowicz Anna , Skibińska Maria , Wiłkość Monika , Tomaszewska Marta , Hauser Joanna
Published: August 2007

Background: FYN is nonreceptor tyrosine kinase that represents the earliest detectable signaling response after antigen-activated inflammatory cells. Studies in animal models of allergic asthma have shown that inhibitors of tyrosine kinases exert an anti-inflammatory effect. In the FYN gene, several polymorphisms have been described. There have, however, been no studies analyzing the impact of FYN gene polymorphisms on the course and severity of asthma. The aim of this study was to analyze the possible relationship between three polymorphisms (–93A/G, Intron10+37C/T and Ex12+894T/G) in the FYN gene and asthma. Methods: We analyzed 120 pediatric asthmatic patients aged from 6 to 18 years. The diagnosis of allergic asthma was based on clinical manifestation, lung function test and positive skin prick tests and/or an increased IgE level. The control group consisted of 187 healthy subjects. The polymorphisms were genotyped with use of the PCR-RFLP method. Results: We observed an association of the –93A/G polymorphism and the presence of asthma (p = 0.014 for genotypes and p = 0.019 for alleles) and in the subgroup of 55 patients with severe asthma (p = 0.042 for genotypes and p = 0.021 for alleles). We also found an association of the Ex12+894T/G polymorphism in the whole group analyzed (p = 0.067 for genotypes and p = 0.024 for alleles), but not in the subgroup with severe asthma. For the Intron10+37T/C polymorphism, we did not find a significant difference between the whole group of asthmatic patients and the control group nor between the subgroup with severe asthma and the control group. In the linkage disequilibrium analysis, we observed a modest linkage between –93A/G and Intron10+37T/C polymorphisms (lod = 18.7, D’ = 0.62, 95% CI: 0.51–0.71, r2 = 0.29); however, it was not strong enough to generate any haplotypes. Conclusions: The results may suggest a relationship between the FYN polymorphisms and allergic asthma.
Skin Testing Correlates Negatively with High-Activity ACP1 *B/*C Genotype
Authors: Greco E. , Bottini N. , Canu G. , Maccari A.M. , Saccucci P. , Gloria-Bottini F. , Fontana L.
Published: August 2007

Background: Previous studies have shown a negative association between ACP1 *B/*C genotype and total IgE level. ACP1 (acid phospatase locus 1) is a polymorphic phosphotyrosine phosphatase that interacts with IL4-RA and is involved in T cell receptor signaling. Methods: In the present paper, we have studied the relationship between *B/*C genotype which shows high ACP1 activity and skin testing in 300 adult subjects referred for allergic manifestations. ACP1 genotypes were determined by DNA analysis. Results: There is a significant negative correlation between the intensity of skin test reaction and *B/*C genotype (p = 0.01). The proportion of *B/*C genotype is lower in allergic subjects with intense skin reaction than in allergic subjects with moderate skin reaction and in healthy controls. Conclusions: This new observation confirms by a different approach the relationship between ACP1 polymorphism and allergic manifestations, suggesting that high ACP1 activity protects against these manifestations.
Standardization of Skin Tests for Diagnosis and Prevention of Hypersensitivity Reactions to Oxaliplatin
Authors: Pagani M. , Bonadonna P. , Senna G.E. , Antico A.
Published: August 2007

Background: Platinum salts can cause allergic sensitization. Recently, hypersensitivity reactions to oxaliplatin, the most recent platinum coordination complex introduced into clinical practice, have been reported. Objective: To validate and standardize skin tests to diagnose and possibly prevent hypersensitivity reactions to oxaliplatin. The secondary aims were to confirm IgE-mediated pathogenesis of the clinical manifestations and to evaluate skin tests to predict patients at risk of hypersensitivity reactions to oxaliplatin. Methods: We performed skin tests atincreasing concentrations of oxaliplatin on 15 patients never exposed to platinum salts, on 10 patients treated with oxaliplatin without any adverse reactions, and on 4 patients who had shown hypersensitivity reactions to the drug. Moreover we performed skin tests on 8 additional patients starting before the 5th dose and following a course of chemotherapy. Results: A positive skin reaction to the prick test at a concentration of 1 mg/ml was seen in 1 patient with hypersensitivity reactions. The intradermal test was positive in all the patients with hypersensitivity reactions at a concentration of 0.1 mg/ml. It was negative in the 15 nonexposed subjects, and in the 10 patients who had been exposed to oxaliplatin without hypersensitivity reactions. The skin test administered to patients before chemotherapy was positive in one case. Conclusion: A skin prick test at a concentration of 1 mg/ml and, in the case of a negative response, an intradermal test at the optimal concentration of 0.1 mg/ml should be used, starting from the 5th course of therapy, to diagnose and prevent hypersensitivity reactions to oxaliplatin.
Relation between Serum Calcium, Phosphate, Parathyroid Hormone and ‘Nondipper’ Circadian Blood Pressure Variability Profile in Patients with Normal Renal Function
Authors: Kanbay Mehmet , Isik Bunyamin , Akcay Ali , Ozkara Adem , Karakurt Feridun , Turgut Faruk , Alkan Rabia , Uz Ebru , Bavbek Nuket , Yigitoglu Ramazan , Covic Adrian
Published: August 2007

Background and Aims: In patients with renal disease, an association between abnormal circadian blood pressure profile and abnormalities in bone and mineral metabolism, including vascular calcifications, is well known. However, such a link has not yet been reported in hypertensive patients with normal renal function. We aimed to evaluate if higher serum phosphate, calcium, parathyroid hormone (PTH) level and the calcium×phosphate (Ca×P) product would be associated with a nondipper hypertension, in patients with normal renal function and without any PTH disorder. Methods: 190 hypertensive subjects with the following inclusion criteria were enrolled: (1) normal phosphate and PTH levels; (2) glomerular filtration rate (GFR) >60 ml/min, and (3) no history of calcium, phosphate, vitamin D medication and hyperparathyroidism. Results: Of the total population, 76 patients (40%) were classified as dippers and 114 (60%) as nondippers. Nondipper patients had higher levels of phosphate (3.70 ± 0.61 vs. 3.35 ± 0.44 mg/dl, p = 0.001), Ca×P product (35.4 ± 6.5 vs. 31.5 ± 5.0, p = 0.001) and PTH (75.7 ± 28.8 vs. 46.6 ± 17.1 pg/ml, p = 0.000) compared to dipper patients. Independent predictors (multiple regression) for nondipper hypertension were PTH (β = 0.43, p = 0.001) and phosphate (β = 0.9, p = 0.03). Conclusion: We demonstrate a graded independent relation between higher levels of phosphate, PTH, Ca×P product and the risk of nondipping in hypertensive patients with an estimated GFR of >60 ml/min and normal mineral metabolism.
GPR54 Polymorphisms in Chinese Girls with Central Precocious Puberty
Authors: Luan X. , Yu H. , Wei X. , Zhou Y. , Wang W. , Li P. , Gan X. , Wei D. , Xiao J.
Published: August 2007

Aims: The GPR54 gene has been proved to be important in the process of puberty onset, yet no association study has been performed to evaluate the effect of polymorphisms in the gene on central precocious puberty (CPP). This study was designed to scan for polymorphisms in the GPR54 gene and to investigate the relationships between the genotypes of GPR54 and the disease. Methods: 272 Chinese Han girls diagnosed to be CPP patients were recruited as the case group and 288 unrelated normal Chinese Han girls as the control group. The whole GPR54 gene was directly sequenced in randomly selected case samples, and the polymorphisms identified were genotyped by ligase detection reaction in both groups. Distributions of the polymorphisms and haplotypes were calculated for statistical evaluation. Results: Totally 6 polymorphisms were found in sequencing, one of which is a nonsynonymous mutation, while genotyping declared that another SNP located in the promoter region was statistically related to the disease (p = 0.037). Conclusion: One polymorphism in GPR54 gene might be correlated with some cases of CPP, likely by changes in expression of the receptor, but the moderate p value and the lack of functional data make it hard to confirm the correlation. Further studies on the polymorphisms are needed for the exact mechanism.
Diet-Derived Nutrients Modulate the Effects of Amylin on c-Fos Expression in the Area Postrema and on Food Intake
Authors: Michel Signe , Becskei Csilla , Erguven Elif , Lutz Thomas A. , Riediger Thomas
Published: August 2007

The pancreatic hormone amylin decreases food intake via activation of area postrema (AP) neurons. We investigated whether amylin’s potency to reduce food intake and to induce c-Fos expression in the AP/nucleus of the solitary tract region is affected by the feeding conditions and specifically by the macronutrient composition of the diet. Whereas a low dose of amylin (5 µg/kg s.c.) induced very little c-Fos expression in ad libitum chow fed rats, it caused a strong c-Fos expression in 24-hour food-deprived rats and in rats that received a nutrient-deficient non-caloric mash (NCM; vanilla-flavoured cellulose) 24 h before injection. To reveal the contribution of single nutrients to the low c-Fos expression after chow feeding, amylin-induced c-Fos was analyzed after feeding NCM that was selectively supplemented with glucose, fat (lard), or protein (casein), matching the intake of these nutrients of chow-fed rats. While the rats fed NCM supplemented with glucose or fat displayed an equally strong amylin-induced activation as fasted rats or rats fed plain NCM, a significantly lower c-Fos expression was observed in rats fed a protein-supplemented NCM or a NCM containing all three nutrients. In line with this lower activation, the same dose of amylin failed to reduce food intake in NCM/protein-fed rats, while amylin caused a reduction in feeding when animals received NCM, NCM/glucose, or NCM/fat. Interestingly, amylin effectively reduced food intake in ad libitum chow fed rats despite the low level of amylin-induced c-Fos expression in the AP under these conditions. We conclude that the anorectic potential of amylin may be attenuated by diet-derived proteins, whereas this effect appears to be overridden when the amount of carbohydrates/fat is high relative to the protein content, such as, e.g., in standard chow.
Maintenance of Homeostasis for Thyroid Hormone in the Adult Rat Brain: Possible Involvement of a Nuclear-Mediated Phenomenon
Authors: Kundu Samita , Roy Sumedha , De Jhuma , Biswas Angshuman , Pramanik Mitali , Ray Arun K.
Published: August 2007

During adult-onset peripheral hypothyroidism, the brain maintains normal levels of thyroid hormone for some time through a mechanism of ‘central homeostasis’. Although onset, duration, and termination of such a homeostatic phenomenon have been recently evaluated in rat models, the mechanism behind remains unknown. During our investigation to understand the mechanism further, we injected the protein synthesis blockers actinomycin D and cycloheximide along with propylthiouracil to adult male rats during the days of onset (day 2) and termination (day 20) of the homeostatic mechanism. We evaluated synaptosomal T3 level and neuronal Na+-K+-ATPase and acetylcholinesterase activities along with deiodinase II activity and cyclic adenosine monophosphate level in the cerebral cortex. The results indicated prevalence of unchanged or lower levels of synaptosomal T3 on the 2nd and on the 20th day, respectively. Such a condition has been parallely supported by reflections in cerebrocortical deiodinase II activity and cyclic adenosine monophosphate levels. The activities of cerebrocortical synaptosomal Na+-K+-ATPase and acetylcholinesterase, which are the two important physiological parameters for neuronal function, have been found to be supportive of the involvement of a neuronal protein-mediated factor in the ‘on’ and ‘off’ reactions in central homeostasis during peripheral hypothyroidism. The results of our study indicate that the expression of ‘central thyroid hormone homeostasis’ is a genomic nuclear-mediated mechanism.
An Interactive Association of Common Sequence Variants in the Neuropeptide Y Gene With Susceptibility to Ischemic Stroke
Authors: Lee Chaeyoung , Kong Minyoung
Published: August 2007

Background and Purpose—

Knowledge of the genetic architecture of ischemic stroke has been quite limited. Most significant associations of candidate genes with ischemic stroke have been difficult to replicate. This might be because the associations were not strong enough for results to be consistent, and testing a mixture of heterogeneous ischemic strokes might lead to confounded genetic associations.

Methods—

A preliminary association analysis with 28 sequence variants in 18 candidate genes (
ACE, AGT, AGTR1, BDNF, CRP, F13B, LIF, MMP9, NPPA, NPY, PTGS2, SELP, SERPINE1, SREBF2, TFPI, THBD, VCAM1
, and
VEGF
) revealed that
NPY
might be the most responsible for the susceptibility of ischemic stroke. Forty-five variants were discovered in the
NPY
gene by full sequencing, and 5 polymorphisms were selected based on their allele frequency and linkage disequilibrium estimates to conduct a thorough examination of their associations with ischemic stroke and its subtypes classified by TOAST. This study was conducted with 271 patients with ischemic stroke and 455 control subjects.

Results—

In contrast to a slight significance for an allelic association with ischemic stroke, remarkable discrepancies between haplotype frequencies of control subjects and patients were found. Especially, TA and CC of the haplotypes composed of C4112T and A6411C in the
NPY
gene were associated with increased risk (
P
=1.8×10
−21
,
P
=2.0×10
−13
). The interchanged haplotypes, TC and CA, were protective against the diseases (
P
=9.3×10
−12
,
P
=6.0×10
−17
). The associations were also shown in major subtypes of ischemic stroke.

Conclusions—

This remarkable haplotypic association suggested that the interaction between the 2 common sequence polymorphisms in
NPY
contributed to a great amount of phenotypic variability of ischemic stroke.
Erythropoietin Promotes Neuronal Replacement Through Revascularization and Neurogenesis After Neonatal Hypoxia/Ischemia in Rats
Authors: Iwai Masanori , Cao Guodong , Yin Wei , Stetler R. Anne , Liu Jialing , Chen Jun
Published: August 2007

Background and Purpose—

Erythropoietin (EPO) has been well characterized and shown to improve functional outcomes after ischemic injury, but EPO may also have unexplored effects on neurovascular remodeling and neuronal replacement in the neonatal ischemic brain. The current study investigates the effects of exogenous administration of EPO on revascularization and neurogenesis, 2 major events thought to contribute to neuronal replacement, in the neonatal brain after hypoxia/ischemia (H/I).

Methods—

Seven-day-old rat pups were treated with recombinant human EPO or vehicle 20 minutes after H/I and again on postischemic days 2, 4, and 6. Rats were euthanized 7 or 28 days after H/I for evaluation of infarct volume, revascularization, neurogenesis, and neuronal replacement using bromodeoxyuridine incorporation, immunohistochemistry, and lectin labeling. Neurological function was assessed progressively for 28 days after H/I by gait testing, righting reflex and foot fault testing.

Results—

We demonstrate that exogenous EPO-enhanced revascularization in the ischemic hemisphere correlated with decreased infarct volume and improved neurological outcomes after H/I. In addition to vascular effects, EPO increased both neurogenesis in the subventricular zone and migration of neuronal progenitors into the ischemic cortex and striatum. A significant number of newly synthesized cells in the ischemic boundary expressed neuronal nuclei after EPO treatment, indicating that exogenous EPO led to neuronal replacement.

Conclusions—

Our data suggest that treatment with EPO contributes to neurovascular remodeling after H/I by promoting tissue protection, revascularization, and neurogenesis in neonatal H/I-injured brain, leading to improved neurobehavioral outcomes.