bluuebunny/crossref_metadata_2025 huggingface dataset:
Reported Hearing Impairment in Essential Tremor: A Population-Based Case-Control Study
Authors: Benito-León Julián , Louis Elan D. , Bermejo-Pareja Félix
Published: December 2007

In a population-based sample, we determined whether a larger proportion of essential tremor (ET) cases reported hearing impairment compared with controls. Ninety-six (38.7%) of 248 ET cases versus 1,371 (29.4%) of 4,669 controls (p = 0.002) reported hearing impairment. In a logistic regression analysis adjusted for age, gender, educational level, depressive symptoms, and dementia, participants who reported hearing impairment were 30% more likely to suffer from ET than were controls (odds ratio 1.3; 95% confidence interval 1.01–1.7; p = 0.04). ET seemed to be associated with reported hearing impairment. The basis for this finding, which has been noted in several studies, deserves further exploration.
Oxidized Low-Density Lipoprotein Biomarkers in Patients with End-Stage Renal Failure: Acute Effects of Hemodialysis
Authors: Bossola Maurizio , Tazza Luigi , Merki Esther , Giungi Stefania , Luciani Giovanna , Miller Elizabeth R. , Lin Edward B. , Tortorelli Antonio , Tsimikas Sotirios
Published: December 2007

Objective: To assess the effect of end-stage renal failure on oxidized low-density lipoprotein (OxLDL) biomarkers and the acute effects of hemodialysis. Oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles (OxPL/apoB) have been associated with cardiovascular disease and new cardiovascular events. Patients with end-stage renal failure have increased oxidative stress and are at significantly increased risk of cardiovascular disease. Methods and Results: Fifty-two stable patients with end-stage renal failure undergoing chronic hemodialysis were included in the study. Pre and post hemodialysis blood samples were obtained for measurement of OxLDL biomarkers: oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles (OxPL/apoB) measured by antibody E06, IgG and IgM autoantibody titers to copper-oxidized LDL (Cu-OxLDL) and malondialdehyde (MDA)-LDL, IgG and IgM apolipoprotein B-100-immune complexes (IC/apoB). Traditional laboratory variables as well as C-reactive protein (CRP) and lipoprotein(a) [Lp(a)] were also measured. For the baseline variables, the distribution of OxPL/apoB and Lp(a) were skewed to lower values, and a strong correlation was noted between OxPL/apoB and Lp(a) (r = 0.94, p < 0.0001). No major associations were noted between OxLDL biomarkers and age, gender or dialytic age. There were also no correlations between OxLDL biomarkers and traditional risk factors, CRP, body mass index, serum creatinine, hypertension or intravenous iron therapy. Following dialysis, there as a significant reduction in OxPL/apoB (–7.5%, p = 0.048) and triglyceride levels (–10.8%, p = 0.005). All other OxLDL biomarkers, CRP, total cholesterol, LDL-C, HDL-C and apoB-100 increased significantly (range 6.3–26.9%, p value range 0.005 to <0.0001). Total protein plasma levels increased 8.8% (p = 0.014 compared to predialysis) following dialysis, consistent with a hemoconcentration effect of hemodialysis. Conclusion: In end-stage renal failure patients undergoing hemodialysis, a reduction in OxPL/apoB levels was noted, despite the hemoconcentrating and strong pro-oxidant milieu of hemodialysis. Studies in larger populations of end-stage renal failure patients are needed to assess whether these findings predict future clinical outcomes.
Familial Membranous Nephropathy: An X-Linked Genetic Susceptibility?
Authors: Bockenhauer Detlef , Debiec Hanna , Sebire Neil , Barratt Martin , Warwicker Paul , Ronco Pierre , Kleta Robert
Published: December 2007

Background: Membranous nephropathy (MN) is the most common histological diagnosis in adults with nephrotic syndrome and a leading cause of end-stage kidney failure from glomerulonephritis. Little is known about the underlying aetiology, although anti-glomerular antibodies have been implicated. No specific underlying genetic defect has yet been identified. Methods: In a family with four members in three generations affected by primary MN, the serum of affected members and their mothers were assessed for anti-glomerular antibodies. Results: All four affected are male and connected through the maternal line, indicative of X-linked inheritance. Age of onset of nephrotic syndrome varied between 1 and 67 years of age, suggesting that a potential underlying gene may confer a genetic predisposition to MN, but other factors, genetic or environmental, are necessary to trigger the disease. Serologic studies revealed antibodies against glomerular and peritubular endothelial cells in the mother of the youngest patient. Conclusions: We have identified the largest reported family with a potential X-linked susceptibility to MN. Foeto-maternal alloimmunization may have triggered the disease in the youngest individual. Considering that the majority of patients with sporadic MN are male, identification of an X-linked predisposing factor may have implications well beyond this family and could provide a target for treatment.
Streptococcus pneumoniae Adherence in Rats under Different Degrees and Durations of Cigarette Smoke
Authors: Özlu Tevfik , Çelik Ilknur , Öztuna Funda , Bülbül Yılmaz , Özsu Şavas
Published: December 2007

Background: Bacterial adherence to buccal epithelial cells in chronic smokers has been reported to increase in vitro. However, it is unclear whether such adherence increases in hosts without epithelial changes linked to chronic smoking. Objective: This was an in vivo investigation of whether or not there was a change in the Streptococcus pneumoniae adherence to buccal epithelial cells of rats exposed to different periods and degrees of environmental cigarette smoke. Method: Eighteen rats were divided into acute and chronic exposure groups, each containing 9 rats. Both groups were further divided into 3 subgroups each, which were exposed to low or high levels of cigarette smoke, or none at all. After the administration of smoke, S. pneumoniae (ATCC 49619) was inoculated into the buccal mucosa. One hour later, buccal epithelial cell samples were taken and the number of bacteria adhering to 40 buccal epithelial cells was counted. Pre- and postinoculation values and the groups administered smoke and the control groups were then compared. Results: A significant increase in Gram-positive diplococci adherence was determined in all groups after S. pneumoniae inoculation. S. pneumoniae was observed to adhere to buccal epithelial cells in all the control group rats and in those in the groups exposed to cigarette smoke. Pneumococcal adherence in the chronic exposure subgroups increased approximately 4-fold with low smoke exposure (p < 0.004) and approximately 7-fold with high smoke exposure (p < 0.0005). Conclusion:S. pneumoniae adherence was significantly high in rats chronically exposed to a high level of cigarette smoke, but not in the acute exposure groups.
Parenchymal and Vascular Interactions in the Pathogenesis of Nonspecific Interstitial Pneumonia in Systemic Sclerosis and Idiopathic Interstitial Pneumonia
Authors: Franco de Carvalho Erika , Parra Edwin Roger , de Souza Romy , Muxfeldt A’b Saber Alexandre , Capelozzi Vera Luiza
Published: December 2007

Background: Interstitial lung disease is a well-recognized prognostic factor in systemic sclerosis (SSc). As the prognosis in nonspecific interstitial pneumonia (NSIP) has been described to be better in collagen vascular disorders compared to the idiopathic forms, we hypothesize that the mechanisms of repair and remodeling are different between these 2 forms of the disease. Objectives: To compare the mechanisms of repair and remodeling between SSc-associated NSIP and the idiopathic form, its impact on pulmonary function tests and survival rates. Methods: We analyzed 18 biopsies from patients with NSIP associated with SSc and 22 with idiopathic NSIP and compared the epithelial and vascular densities as well as vascular activity. Results: Epithelial cell density was lower in SSc-NSIP when compared with idiopathic NSIP (p < 0.0001). Type II pneumocytes and Clara cells were reduced in idiopathic NSIP (p = 0.02). A decrease in microvessel density was found in SSc-NSIP compared to idiopathic NSIP (p < 0.0001). The vascular activity measured by VCAM expression was higher in NSIP-SSc when compared to the idiopathic group (p < 0.0001). The DLCO/VA in SSc-NSIP was more compromised. A direct association between vascular density and DLCO/VA was found (p = 0.02). There was no difference in the survival rate between the 2 groups after a follow-up of 36 months. Conclusions: Alterations in the epithelium and vasculature seem to differ in the pathogenesis of SSc-NSIP when compared to the idiopathic form of the disease. Further studies may be required to assess the significance of these findings and explore if they can provide prognostic and/or treatment information.
Differences in the Glomerular Filtration Rate Calculated by Two Creatinine-Based and Three Cystatin-C-Based Formulae in Hospitalized Elderly Patients
Authors: Ramel Alfons , Jonsson Palmi V. , Bjornsson Sigurbjorn , Thorsdottir Inga
Published: December 2007

Background: Reduced renal function is a health problem in elderly patients. Different creatinine- and cystatin-C-based formulae have been used to estimate glomerular filtration rate (GFR). Aims: To investigate individual and group differences of GFR estimates derived from five different formulae. Methods: 60 patients were randomly assigned to participate in this cross-sectional study. Nutrition status was assessed, blood samples were drawn and GFR was calculated using two creatinine- and three cystatin-C-based formulae. Results: Four of five formulae indicate reduced GFR in >70% of the participants, GFR was significantly less in malnourished patients according to one creatinine formula. Estimates from the formulae were highly correlated (r = 0.607–0.863, p < 0.001), but individual differences were between –36.1 and 79.9 ml/min/1.73 m2. The formulae grouped 38.3–60.0% of the subjects differently into the five stages of chronic kidney disease. BMI, total cholesterol, age and gender were significant predictors for the calculated GFR differences between the formulae. Conclusion: The prevalence of reduced renal function is high in elderly hospitalized patients. BMI, age and/or gender can affect GFR estimates depending on the formula used, and there is an association between total cholesterol and calculated GFR differences between formulae. Different formulae can result in a different grouping of patients into the five stages of chronic renal disease.
Mortality in Individuals with Mild Cognitive Impairment
Authors: Guehne Uta , Luck Tobias , Busse Anja , Angermeyer Matthias C. , Riedel-Heller Steffi G.
Published: December 2007

Objective: This study aimed to investigate whether mortality is higher for individuals suffering from Mild Cognitive Impairment (MCI). Methods: A community sample of 1,045 dementia-free individuals aged 75 years and over was examined using neuropsychological tests over a 4.5-year period. Data were analyzed with the Cox proportional hazards model after having been adjusted for age, gender, and incident dementia. Results: Association between MCI and mortality was examined subject to varied diagnostic criteria of MCI. We found an increased risk of death that was about 1.5 times higher for individuals with MCI when a cognitive performance of more than 1.5 standard deviation below the mean of age- and education-matched controls was required and the criterion of a cognitive complaint was excluded. Males were at about a 40% increased risk of death. Risk also increased with age by about 8% per year. Incident dementia showed a significant influence on mortality only if it became manifest by 1.5 years after the baseline measurement (follow-up 1). Conclusion: MCI is associated with increased mortality when certain diagnostic criteria are applied.
Photoperiod Influences the Central Effects of Ghrelin on Food Intake, GH and LH Secretion in Sheep
Authors: Harrison Joanne L. , Miller David W. , Findlay Patricia A. , Adam Clare L.
Published: December 2007

Ghrelin is a circulating peptide, primarily secreted by the gut, that has reported actions within the hypothalamo-pituitary axis to stimulate food intake, inhibit GnRH/LH secretion and stimulate GH secretion in monogastric species. Here, we examine responses to centrally administered ghrelin in a seasonal ruminant. Estradiol-implanted castrated male sheep with indwelling intracerebroventricular (i.c.v.) cannulae were kept with unrestricted food for 16 weeks in long day photoperiod (LD, 16 h light/day) then 16 weeks in short days (SD, 8 h light/day). In week 16 of each photoperiod they were given a control (saline) i.c.v. injection on day 1 and ghrelin i.c.v. injection on day 2. Mean circulating endogenous plasma ghrelin concentrations showed no diurnal pattern and were similar between the photoperiods. Central ghrelin injection increased voluntary food intake 2-fold in the first hour after administration in LD but not in SD, decreased LH pulse frequency and amplitude in SD but not in LD, and stimulated GH release in both photoperiods, although there was a 1.5-fold larger response in LD. Therefore, central injection of ghrelin to sheep acutely stimulated food intake in LD, suppressed reproductive neuroendocrine output in SD, and stimulated GH secretion irrespective of photoperiod, although more pronounced in LD. These data indicate that photoperiod can influence hypothalamic appetite and reproductive neuroendocrine responses to ghrelin in seasonal species.
Effect of Climatic Temperature on Fluid Gain in Hemodialysis Patients with Different Degrees of Overhydration
Authors: Hwang Jyh-Chang , Wang Charn-Ting , Chien Chih-Chiang
Published: December 2007

Background: To assess the effect of seasonal temperature on the interdialytic body weight gain (ΔBW), %ΔBW/dry weight (DW), and pre-dialysis blood pressure in chronic hemodialysis (HD) patients with different degrees of overhydration. Method: Year 2005 was divided into two seasons: ‘cold’ (the coolest 5 months) and ‘hot’ (the hottest 5 months). A total of 221 end-stage renal disease patients treated with HD at our center throughout the year 2005 were enrolled. Results: ΔBW showed a reversed trend to the water evaporation rate, which paralleled temperature change. Increases of ΔBW and %ΔBW/DW in cold weather were more significant in non-diabetes mellitus than diabetes mellitus. Only patients in the bottom two quartiles for %ΔBW/DW in hot weather (i.e., <5%) showed a cold weather-induced increase in %ΔBW/DW. Conclusion: A cold weather-induced increase in fluid accumulation occurs in only those patients with less hypervolemia during the hot season.
Autosomal Dominant Polycystic Kidney Disease: Recent Advances in Pathogenesis and Treatment
Authors: Chang Ming-Yang , Ong Albert C.M.
Published: December 2007

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder affecting 1 in 1,000 people in the general population and accounts for up to 10% of all patients on renal replacement therapy. Numerous fluid-filled epithelial cysts arise from different nephron segments as spherical dilatations or small out-pouchings, enlarge progressively and eventually become disconnected from the rest of the renal tubule. The development of cysts is accompanied by destruction of the renal parenchyma, interstitial fibrosis, cellular infiltration and loss of functional nephrons. ADPKD is not only a kidney disease but also a systemic disorder associated with intracranial arterial aneurysms, cardiac valvular defects, colonic diverticulosis and cyst formation in other organs such as the liver, spleen and pancreas. The identification of PKD1 and PKD2 together with the drive to elucidate the functions of their encoded proteins, polycystin-1 (PC1) and polycystin-2 (PC2), has led to an explosion of clinical and scientific interest in this common disorder. The aim of this review is to highlight recent advances in our understanding of ADPKD pathogenesis which are leading to exciting new treatment strategies.
A Neonatal Swine Model of Allergy Induced by the Major Food Allergen Chicken Ovomucoid (Gal d 1)
Authors: Rupa Prithy , Hamilton Korinne , Cirinna Melissa , Wilkie Bruce N.
Published: December 2007

Background: Food allergy is a serious health problem for which a validated outbred large animal model would be useful in comparative investigations of immunopathogenesis and treatment and in testing hypotheses relevant to complex host-environmental interactions in predisposition to and expression of food allergy. Objective: To establish a neonatal swine model of IgE-mediated allergy to the egg protein ovomucoid (Ovm) that may mimic human allergy. Methods: In order to induce Ovm sensitivity, piglets at days 14, 21 and 35 of age were sensitized by intraperitoneal injection of 100 µg of crude Ovm and cholera toxin (50, 25 or 10 µg). Controls received 50 µg of cholera toxin in phosphate-buffered saline. The animals were challenged orally on day 46 with a mixture of egg white and yoghurt. Outcomes were reported as direct skin tests, clinical signs, IgG-related antibody and passive cutaneous anaphylaxis. Results: Sensitized pigs developed immediate wheal and flare reactions, and after oral challenge, sensitized but not control animals displayed signs of allergic hypersensitivity. Serum IgG-related, Ovm-specific antibodies were detected only in the sensitized pigs and IgE-mediated antibody response to Ovm was confirmed by positive passive cutaneous anaphylaxis reactions induced by sera of sensitized but not by heat-treated sera from Ovm-sensitized pigs or sera of unsensitized control pigs. Conclusion: The present results confirm induction of Ovm-specific allergy in pigs and provide opportunity to investigate allergic predisposition and immunopathogenesis of IgE-induced Ovm allergy using outbred neonatal swine. This may better simulate allergic disease in humans and allow investigation of candidate prophylactic and therapeutic approaches.
Measurement of Lipid Transfer Protein in 88 Apple Cultivars
Authors: Sancho Ana I. , van Ree Ronald , van Leeuwen Astrid , Meulenbroek Bert J. , van de Weg Eric W. , Gilissen Luud J.W.J. , Puehringer Helene , Laimer Margit , Martinelli Alessio , Zaccharini Marzio , Vazquez-Cortés Sonia , Fernandez-Rivas Montserrat , Hoffmann-Sommergruber Karin , Mills E.N. Clare , Zuidmeer Laurian
Published: December 2007

Background: Fruits are a major cause of food allergy in adults. Lipid transfer proteins (LTP) are implicated in severe allergic reactions to fruits, but little is known about LTP content in different cultivars. Objective: Determination of the levels of LTP in a wide range of apple cultivars. Methods: LTP was measured in apples from 53 cultivars grown in Italy and 35 grown in The Netherlands, using three different immunoassays: a competitive ELISA (cELISA), a sandwich ELISA (sELISA) and a RAST inhibition (RI). Selected cultivars were evaluated using the basophil histamine release test (BHR), skin prick test (SPT) and double-blind, placebo-controlled food challenge (DBPCFC). Results: LTP levels measured with the three immunoassays were significantly correlated, as judged by Pearson’s correlation (0.61 < Rp < 0.65; p < 0.0001), but differed with respect to the actual quantities: 3.4–253.2 (sELISA), 2.7–120.2 (cELISA) and 0.4–47.3 µg/g tissue (RI). Between cultivars, LTP titers varied over about a two-log range. Pilot in vitro and in vivo biological testing (BHR, SPT and DBPCFC) with selected cultivars supported the observed differences in LTP levels. Conclusions: Around 100-fold differences in LTP levels exist between apple cultivars. Whether the lowest observed levels of LTP warrant designation as hypo-allergenic requires more extensive confirmation by oral challenges. Determination of cultivar variation in LTP levels provides important information for growers and consumers. Comparison to earlier reported Mal d 1 levels in the same cultivars reveals that a designation as low allergenic does not always coincide for both allergens.
Roles of Galectin-9 in the Development of Experimental Allergic Conjunctivitis in Mice
Authors: Fukushima Atsuki , Sumi Tamaki , Fukuda Ken , Kumagai Naoki , Nishida Teruo , Okumura Ko , Akiba Hisaya , Yagita Hideo , Ueno Hisayuki
Published: December 2007

Background: Galectin-9 was recently identified as a ligand for Tim-3, which negatively regulates Th1 cells. Here, we investigated whether administration of anti-galectin-9 antibodies (Abs) affects the development of murine experimental allergic conjunctivitis (EC), a Th2-mediated disease. Methods: EC was induced in BALB/c mice by active immunization with ragweed (RW) followed by RW challenge in eye drops. Normal rat IgG (nrIgG) or anti-galectin-9 Ab was injected intraperitoneally into the mice either during the induction phase treatment or effector phase treatment. Alternatively, Abs were injected into the subconjunctival space during the effector phase. To evaluate in vitro effects of anti-galectin-9 Abs, splenocytes from RW-sensitized mice were cultured in vitro with RW in the presence of nrIgG or anti-galectin-9 Abs. To induce EC, these splenocytes were transferred into naïve BALB/c mice followed by RW challenge. Results: Treatment with anti-galectin-9 Abs in vivo during either the induction or effector phase did not significantly affect the severity of EC. However, when the splenocytes from RW-primed mice treated with anti-galectin-9 Abs during the induction phase were stimulated in vitro and adoptively transferred into naïve recipients, they induced significantly severer EC. In contrast, when RW-primed splenocytes were restimulated in vitro with RW in the presence of anti-galectin-9 Abs and then adoptively transferred, they induced less severe EC and produced significantly less IL-5 and IL-13 and more IFN-γ compared to nrIgG-treated control splenocytes. Conclusions: These observations may reflect the fact that galectin-9 not only regulates T-cell function, it is also involved in many other biological functions.
Home Exposures to Environmental Tobacco Smoke and Allergic Symptoms among Young Children in Singapore
Authors: Zuraimi M.S. , Tham K.W. , Chew F.T. , Ooi P.L. , David Koh
Published: December 2007

Background: Research relating environmental tobacco smoke (ETS) exposures have focused on childhood asthma. There have been fewer studies with conflicting results performed on associations of ETS exposures with allergic symptoms. We are interested to see if ETS exposures in the homes are associated with allergic symptoms among preschool children in Singapore where public smoking is banned. Methods: A cross-sectional study adopting an expanded and modified ISAAC (International Study on Asthma and Allergies in Childhood) questionnaire for the evaluation of asthma and allergies was conducted on 6,794 children attending 120 randomly selected child care centers. Specific information on demographics and ETS exposures was obtained. Adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) were determined using Poisson multivariate regression with a log-link function and robust variance estimates as recommended for cross-sectional studies. Results: The response proportion was 70.0%, and 4,759 children from 97 centers participated. After adjusting for covariates, it was found that home ETS exposure was associated with increased risks of current symptoms of rhinitis (PR 1.23; 95% CI 1.01–1.50) and rhinoconjunctivitis (PR 1.79; 95% CI 1.26–2.54). These associations followed dose-response trends with respect to number of cigarettes smoked or smokers in the homes. Home ETS exposures were also associated with higher PRs of wheeze, nocturnal cough and doctor-diagnosed asthma. Compared with paternal smoking, higher risks of the above outcomes were found for maternal smoking. Conclusion: Home ETS exposure is a risk factor associated with rhinitis and asthma among preschool children.
Basophil Histamine Release Decreases during Omalizumab Therapy in Allergic Asthmatics
Authors: Noga Oliver , Hanf Gerald , Kunkel Gert , Kleine-Tebbe Jörg
Published: December 2007

Background: Omalizumab is an established add-on therapy efficacious in allergic diseases with additional anti-inflammatory activity in the treatment of asthma. The evaluation of responders to anti-IgE treatment is critical to maximize benefit/risk/cost ratio. The aim of the study was to monitor the efficacy of anti-IgE treatment by ex vivo basophil histamine release. Methods: Seventeen patients with allergic asthma were enrolled and received omalizumab at a dose of ≧0.016 mg/kg/IgE every 4 weeks. Histamine release from basophils was evaluated fluorometrically after dose-dependent allergen challenge at baseline and after 16 weeks of treatment. Maximal histamine release and cellular sensitivity to the allergen were calculated. Clinical measurements consisted of body plethysmography, skin prick test, β2-agonist usage, serum free IgE levels, peripheral eosinophils and investigator ratings of global evaluation of treatment effectiveness. Results: Maximal histamine release and cellular sensitivity to the allergen were significantly decreased in the omalizumab group compared to placebo. These changes were accompanied by significant changes in the clinical markers airway resistance, β-agonist usage, skin prick test wheal area and investigator ratings of global evaluation of treatment effectiveness. Conclusions: Omalizumab therapy decreases basophil histamine release and cellular sensitivity with high effectivity of 95.8% (median). The decline of ex vivo basophil responses does not always parallel individual clinical improvement. Basophil-based stimulation tests should be further evaluated before being regarded as useful parameters monitoring omalizumab therapy.
Immediate Hypersensitivity Elicits Renin Release from Cardiac Mast Cells
Authors: Kano Seiichiro , Tyler Eleanor , Salazar-Rodriguez Mariselis , Estephan Rima , Mackins Christina J. , Veerappan Arul , Reid Alicia C. , Silver Randi B. , Levi Roberto
Published: December 2007

Background: We recently reported that murine and cavian heart mast cells are a unique extrarenal source of renin. Ischemia/reperfusion releases this renin leading to local angiotensin formation and norepinephrine release. As mast cells are a primary target of hypersensitivity, we assessed whether anaphylactic mast cell degranulation also results in renin and norepinephrine release. Methods: Hearts isolated from presensitized guinea pigs were challenged with antigen. Results: Cardiac anaphylaxis was characterized by mast cell degranulation, evidenced by β-hexosaminidase release and associated with renin and norepinephrine release. Mast cell stabilization with cromolyn or lodoxamide markedly attenuated the release of β-hexosaminidase, renin and norepinephrine. Renin inhibition with BILA2157 did not affect mast cell degranulation, but attenuated norepinephrine release. Conclusions: Our findings disclose that immediate-type hypersensitivity elicits renin release from mast cells, activating a local renin-angiotensin system, thereby promoting norepinephrine release. As renin is stored in human heart mast cells, allergic reactions could initiate renin release, leading to local angiotensin formation and hyperadrenergic dysfunction.
A Randomized Controlled Trial of Sublingual Immunotherapy for Japanese Cedar Pollinosis
Authors: Horiguchi Shigetoshi , Okamoto Yoshitaka , Yonekura Syuji , Okawa Toru , Yamamoto Heizaburou , Kunii Naoki , Sakurai Daijyu , Fujimura Takashi , Nakazawa Kazuyoshi , Yasueda Hiroshi
Published: December 2007

Background: Japanese cedar pollen represents an important and unique allergen. Sublingual immunotherapy (SLIT) has been suggested to be a highly effective route of desensitization against a variety of allergens. However, little information is available about its use in cedar pollen allergy. Methods: A blinded randomized, placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a period of 6 months. Sixty-seven subjects were enrolled and the symptom scores during the pollen season were evaluated by a symptom diary, measurement of cedar-specific IgE and IgG4, and determination of Cry j-specific Th2 clones before SLIT and before and after the pollen season. Results: No major adverse effects were observed in either group. The serum-specific IgG4 activity increased significantly after SLIT in the active group. The active group also exhibited significantly lower symptom scores compared to the placebo. The specific Th2 clone sizes were not significantly different between the groups before the pollen season. However, an increase in the clone size was observed after the pollen season in the placebo group, but not in the active group. Conclusion: Use of SLIT for Japanese cedar pollinosis was found to be safe and associated with an increase in cedar-specific IgG4 levels. Such therapy inhibited the increase in Cry j-specific Th2 clone size induced by pollen exposure. Finally, use of SLIT resulted in significant improvement of the clinical symptoms of cedar pollinosis in this patient population. These observations suggest that SLIT may offer another safe approach to the management of cedar pollinosis.
Anaphylaxis from the Influenza Virus Vaccine
Authors: Coop Christopher A. , Balanon Synya K. , White Kevin M. , Whisman Bonnie A. , Rathkopf Melinda M.
Published: December 2007

Background: Allergic reactions to the influenza vaccine are uncommon and usually associated with sensitivity to egg or gelatin. The aim of this study was to report the case of anaphylaxis to the influenza vaccine. Methods: Allergy percutaneous skin testing, serum specific IgE testing and IgE immunoblotting were performed to the influenza vaccine, egg, and gelatin. Results: Percutaneous skin testing to the influenza vaccine and gelatin were positive and egg (white, whole, and yolk) was negative. Immunocap® serum-specific IgE testing to egg (white, whole, and yolk) and gelatin were negative (<0.35 kU/l). IgE immunoblots were performed with 2 cord blood serums and the patient’s serum at a 1:20 dilution against 10 µg of the Fluzone influenza vaccine. The patient’s IgE immunoblot showed a protein band at 100 kDa which is similar to the molecular weight of gelatin protein, a 68-kDa protein which is similar to the molecular weight of hemagglutinin protein from the influenza vaccine, and a 45-kDa protein band that is similar to the molecular weight of ovalbumin protein from chicken embryo/egg. Conclusion: Based on clinical symptoms, skin testing, Immunocap testing and immunoblot evaluation, we feel that our patient is allergic to the infectious agent in the influenza vaccine as well as gelatin and ovalbumin in egg.
Persistent Agonist-Induced Vasoconstriction Is Not Required for Angiotensin II to Mediate Inward Remodeling of Isolated Arterioles with Myogenic Tone
Authors: Martinez-Lemus Luis A.
Published: December 2007

Norepinephrine (NE, 10–5.5 M) exposure for 4 h induces tone augmentation and vasodilation impairment after its removal. These changes are believed to represent early stages of inward remodeling. The hypothesis was tested that adrenoceptors causing vasoconstriction are responsible for NE-induced maintenance of augmented tone and vasodilation impairment, and that other vasoconstrictors associated with in vivo inward remodeling, a condition in which the internal passive diameter of arterioles is reduced without changes in medial cross-sectional area, also induce these changes in isolated arterioles. α-Adrenoceptor blockade prevented tone augmentation and vasodilation impairment, while β-adrenoceptor blockade allowed NE to induce those changes plus inward remodeling. Endothelin-1 (10–8 M) induced tone augmentation and vasodilation impairment. Angiotensin II (ANG-II, 10–7 M) and platelet-derived growth factor (10 ng/ml) did not. ANG-II did not cause sustained vasoconstriction, but induced inward remodeling dependent on presence of myogenic tone and tyrosine phosphorylation. Thus, prolonged vasoconstriction is not required during ANG-II-induced inward remodeling, suggesting remodeling processes effected by different agonists vary, with tone augmentation and impaired vasodilation occurring when vasoconstriction is required. This stresses the dynamic structure of arterioles, with rapid remodeling possibly involving functional changes and changes in extracellular matrix, cellular attachments, and/or cytoskeletal structures.
Fibroblast Growth Factor Receptor 2 Plays an Essential Role in Telencephalic Progenitors
Authors: Ever Leah , Zhao Rui-jing , Eswarakumar Veraragavan P. , Gaiano Nicholas
Published: December 2007

We used loss-of-function analysis to determine the role of fibroblast growth factor receptor 2 (FGFR2) in telencephalic progenitors, and also to examine interactions between FGFR and Notch signaling. While the telencephalon of FGFR2 mutants appears grossly normal, mutant telencephalic progenitors exhibit altered proliferative behavior in vivo and in vitro. Based upon our prior finding that Notch1 activation increased neurosphere frequency in FGF2, we tested whether this effect is mediated by FGFR1 or FGFR2. We found that Notch1 activation increased neurosphere frequency in cells mutant for either FGFR1 or FGFR2, but had no effect on the reduced size of neurospheres mutant for those receptors. Additional analyses revealed biochemical changes in the adult neocortex mutant for the IIIc isoform of FGFR2, and essential roles for FGFR2 in nasopharynx, eyelid, and cornea development.
Serum Albumin, Body Weight and Inflammatory Parameters in Chronic Hemodialysis Patients: A Three-Year Longitudinal Study
Authors: Bossola Maurizio , La Torre Giuseppe , Giungi Stefania , Tazza Luigi , Vulpio Carlo , Luciani Giovanna
Published: December 2007

Backgrounds and Aims: The present study aimed at making prospective longitudinal measurements of nutritional and inflammatory parameters to determine whether nutritional and inflammatory status decline or increase over time in a cohort of prevalent hemodialysis patients, and to evaluate which factors influence eventual changes. Patients: 64 hemodialysis patients were followed at 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months. At each follow-up visit, dry body weight, serum albumin, serum total cholesterol, total white blood cells, total lymphocyte count, serum glucose, C-reactive protein, ferritin, fibrinogen, hemoglobin, and weekly erythropoietin dose were assessed. Main Outcome Measures: Changes in nutritional and inflammatory parameters over time. Results: 43 patients completed the study at 36 months. Mean serum albumin levels (g/dl) improved significantly between baseline (3.76 ± 0.24) and 36 months (3.93 ± 0.27) (F = 4.005; p = 0.0009). Dialytic age was significantly associated with changes of serum albumin (F = 2.797; p = 0.028). The mean dry weight slightly remained stable over time (F = 1.473; p = 1.0) as well as the level of total cholesterol (p = 0.77) and lymphocyte count (F = 1.539; p = 0.186). Over time, the levels of C-reactive protein tended to decrease, although the differences were not statistically significant (F = 1.332; p = 0.19). Over time, the serum level of fibrinogen (F = 0.422; p = 0.17) and ferritin (F = 0.314; p = 0.52) remained stable. The number of white blood cells significantly decreased over time (F = 4.691; p = 0.0079) and dialytic age (F = 3.214; p = 0.015) was the variable significantly associated with such decline. The hemoglobin levels (F = 1.423; p = 0.14) and the weekly erythropoietin dose did not change significantly during the study (F = 1.019; p = 0.61), nor did the serum glucose levels (F = 1.231; p = 0.10). Conclusion: These results support the hypothesis that end-stage renal disease and HD are not necessarily associated with deterioration of the nutritional status over time.
Analysis of the Respiratory Chain in Ethanologenic Zymomonas mobilis with a Cyanide-Resistant bd-Type Ubiquinol Oxidase as the Only Terminal Oxidase and Its Possible Physiological Roles
Authors: Sootsuwan Kaewta , Lertwattanasakul Noppon , Thanonkeo Pornthap , Matsushita Kazunobu , Yamada Mamoru
Published: December 2007

The respiratory chain of the ethanologenic bacterium Zymomonas mobilis was investigated, in which the pyruvate-to-ethanol pathway has been demonstrated to be mainly responsible for NADH oxidation and the tricarboxylic acid cycle is incomplete. Membranes from cells cultivated under aerobic or anaerobic growth conditions showed dehydrogenase and oxidase activities for NADH, D-lactate and D-glucose and ubiquinol oxidase activity. Intriguingly, the NADH oxidase activity level of membrane fractions from cells grown aerobically was found to be higher than that of membrane fractions from Escherichia coli or Pseudomonas putida grown aerobically, indicating a crucial role of the respiratory chain in NADH oxidation in the organism. Cyanide-resistant terminal oxidase activity was observed and appeared to be due to a bd-type ubiquinol oxidase as the only terminal oxidase encoded by the entire genome. The terminal oxidase with a relatively strong ubiquinol oxidase activity exhibited remarkably weak signals of cytochrome d. Considering these findings and the presence of a type-II NADH dehydrogenase but not a type-I, a simple respiratory chain that generates less energymay have evolved in Z. mobilis.
Platelet functions and clinical effects in acute myelogenous leukemia
Authors: Bruserud Øystein , Foss Brynjar
Published: December 2007

Platelets interact with normal peripheral blood cells via adhesion as well as soluble mediators, and platelet released mediators can affect hematopoietic stem and progenitor cells. Interactions may also be involved between platelets and circulating malignant cells, which is suggested by the effects platelets seem to have on metastasis and the various platelet abnormalities observed in various malignant disorders, including acute myelogenous leukemia (AML) and other leukemias. It is only recently that the interactions between platelets and AML cells have been characterized in detail, and studies show that; i) platelets and AML blasts can affect functional characteristic of each other, ii) chemotherapeutic drugs frequently used in AML therapy can alter several platelet functions, iii) the systemic levels of various cytokines are enhanced during AML chemotherapy, including cytokines known to affect both leukemic blasts and platelet activation, and iv) platelet secretion of growth factors are clearly detected in peripheral blood stem cells autografts. In this review we describe platelet interactions with normal leukocytes, normal hematopoietic and leukemic cells and the possible clinical relevance of these interactions in AML.
Fondaparinux for the treatment of patients with acute heparininduced thrombocytopenia
Authors: Finch Christopher , Howard Amanda , Minhas Sohail , Lobo Bob
Published: December 2007

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. We prospectively treated seven subjects with acute HIT with fondaparinux and compared the results to a similar historical control population from the same hospital. Six of the seven fondaparinux-treated subjects were transitioned to warfarin, beginning after platelet count recovery occurred. Ten historical controls were treated with a direct thrombin inhibitor (DTI), eight of which were transitioned to warfarin. The primary study outcome was platelet count recovery which was defined as an increase from baseline by at least 30% of nadir to greater than 100,000/mm3 by day seven. Seven subjects were prospectively treated with fondaparinux for a median of eight days. Six of the seven had HIT with thrombosis at the time of enrollment. All fondaparinux treated subjects had a complete platelet count recovery, and none experienced a new thromboembolic complication, major bleeding or death by week four. One subject underwent limb amputation. Ten historical controls were treated with a DTI for a median duration of eleven days. Platelet count recovery occurred in eight of the ten historical controls. No new thromboembolic complications or major bleeds occurred but limb gangrene occurred in four controls. The development of limb gangrene in the historical controls may have been a result of delayed recognition of HIT and/ or inappropriately early institution of warfarin in the historical controls. This pilot study suggests that fondaparinux may be useful in patients with acute HIT.
High-dose atorvastatin in peripheral arterial disease (PAD): Effect on endothelial function, intima-media-thickness and local progression of PAD
Authors: Simon Roger , Loo Bernd van der , Kovacevic Tamara , Brockes Christiane , Rousson Valentin , Amann-Vesti Beatrice , Spring Silviana , Koppensteiner Renate
Published: December 2007

Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin (80 mg/day) have been demonstrated in patients with coronary and cerebrovascular disease. The impact of such a therapy in patients with peripheral arterial disease (PAD) is less known so far. Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function, common carotid intima-media thickness (IMT) and local progression of PAD in these patients. One hundred of 500 patients screened with documented PAD were randomly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment. Ninety-six percent of patients in the control group were on standard statin treatment. High resolution B-mode ultrasonography was used to study brachial artery flowmediated dilation (FMD), IMT and ankle-brachial index (ABI) at baseline and at six months. FMD and IMT at baseline and at six months were 4.1 (0.06–8.6) versus 5.0 (0.76 vs. 8.1) %, p=0.96, and 0.76 (0.66–0.82) versus 0.73 (0.63–0.81) mm, p=0.41, respectively, in the atorvastatin group, and 2.66 (-1.9 – 6.9) versus 3.65 (0.0–8.6)%, p=0.02, and 0.78 (0.71–0.90) versus 0.77 (0.70–0.90) mm, p=0.48,in the control group. ABI at baseline and at six months was not different in either group. LDL cholesterol was reduced from 2.53 (2.21–3.28) to 1.86 (1.38–2.29) mM (p<0.0001) in the atorvastatin group, whereas levels remained stable in the control group [2.38 (1.94–3.16) vs.2.33 (1.82–2.84) mM, p=0.61]. Major adverse cardiovascular events occurred in 2.1% in the atorvastatin group and 1.9% in the control group (p= 0.61). In conclusion, in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD. IMT andABI were also similar in patients with and without high-dose atorvastatin at six months.
Possible contribution of cytomegalovirus infection to the high risk of (recurrent) venous thrombosis after renal transplantation
Authors: Vries Aiko P. J. de , Veeger Nic J. G. M , Son Willem J. van , Bakker Stephan J. L , Meer Jan van der , Lijfering Willem M
Published: December 2007

Renal transplant recipients are at an increased risk of venous thrombosis, which has been regarded as a postoperative complication, although it may persist afterwards. As numerous case reports have shown that active cytomegalovirus (CMV) infection can be found at time of onset of venous thrombosis, and is frequently found in renal transplant recipients, we hypothesized that one might be the result of the other. To calculate the risk of (recurrent) venous thrombosis in renal transplant recipients, and to see whether CMV infection influenced this risk, we retrospectively analysed 606 living consecutive renal transplant recipients. CMV status at time of transplantation and at time of enrolment was determined. Absolute risks of first venous thrombosis and recurrence were compared with CMV status, and were corrected for surgery related venous thrombosis, age, and anticoagulant treatment. Annual incidence of venous thrombosis was 0.88% (95% CI, 0.65–1.15) in all recipients and 0.59% (95% CI,0.41–0.83) corrected for surgery related venous thrombosis. CMV positive and seroconverted recipients tended to have an increased risk of venous thrombosis compared to CMV negative recipients; corrected relative risks were 2.0 (95% CI, 0.9–5.2) and 1.7 (95% CI, 0.6–4.7), respectively. The cumulative 10-year recurrence rate of venous thrombosis in CMV seronegative, seroconverted, and seropositive recipients was 10%,51% and 59%, respectively. We conclude that CMV infection tended to be associated with an increased risk of (recurrent) venous thrombosis. Prospective studies are warranted to establish this observation, which suggests that CMV infection influences the high risk of (recurrent) venous thrombosis in renal transplant recipients.
Thrombophilias and adverse pregnancy outcome – A confounded problem!
Authors: Janssen Nard G , Kalk Jakoba J , Hague William M , Dekker Gustaaf A , Kist Willem J , de Vries Johanna I. P.
Published: December 2007

It was the objective of this study to analyse the influence of confounders, such as ethnicity, severity of illness and method of testing, in articles concerning the still moot relationship of thrombophilias to adverse pregnancy outcome (APO). Relevant casecontrol studies were identified using Medline and EMBASE databases between 1966 and 2006. Search terms were recurrent fetal loss, intrauterine fetal death, preeclampsia, HELLP-syndrome, eclampsia, fetal growth restriction, abruptio placentae, combined with maternal thrombophilias. Data was extracted from the articles per subgroup ofAPO regardless of confounder. These subgroups were tested if they fulfilled the heterogeneity testing criterion (I2 > 35%) to weigh the influence of the confounder. Confounders were selected and examined with Mantel- Haenszel method. Increased thrombophilia prevalence was confirmed in most adverse pregnancy outcomes. Ethnicity, genetic testing only and severity of illness were confounders in the various forms of APO. Stronger relationships between factor V Leiden and severity of disease were found in 2nd and 3rd trimester than 1st trimester recurrent fetal loss, in preeclampsia with: blood pressure ≥160/110 mmHg than ≥140/90 mmHg; proteinuria ≥5 grams per day than < 5 grams; onset before than after 28 weeks, in fetal growth restriction <3rd percentile than <5th, than <10th, and in earlier occurrence of abruptio placentae than 3rd trimester. In conclusion, reports on the prevalence of maternal thrombophilias and APO are influenced by various confounders, which are not always appropriately analysed. The differences we have identified reflect the differential impact of these confounders. These data emphasise the importance of more uniform research.