bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Neuroimmunomodulation in Aging
Authors: De la Fuente Mónica
Published: November 2008

Aging is accompanied by an impairment of the physiological systems including the nervous, endocrine and immune systems, as well as of the nervous-immune communication. This impairment could explain the loss of homeostasis as well as the increased morbidity and mortality that appear with age. In the context of neuroimmunomodulation, it is now accepted that the age-related impairment of immune functions is the cause of the increased vulnerability to infection, cancer and autoimmune diseases of aged animals. Moreover, since the functional capacity of the immune cells has been proposed as a marker of health, our group, using mice with premature senescence, long-lived mice and human centenarians, has ascertained that several immune functions are good markers of biological age and predictors of longevity. Surprisingly, although there is presently considerable research on the changes of the immune system with age, denominated immunosenescence, the data supporting the role of this system in aging are very scarce. With aging, the immune cells show an increase in oxidant and inflammatory compounds and a decrease in antioxidant defenses, which is more evident in phagocytic cells. This chronic oxidative stress, which has among its intracellular mechanisms the activation of NF-ĸB in the leukocytes, affects all cells and especially those of the regulatory systems. Thus, we have proposed a key involvement of oxidative changes of the immune system in aging. Accordingly, the administration of antioxidants improves both the nervous and immune functions, decreasing their oxidative stress, and consequently there is a significant increase in longevity.
Immunosenescence and Immunogenetics of Human Longevity
Authors: Ostan R. , Bucci L. , Capri M. , Salvioli S. , Scurti M. , Pini E. , Monti D. , Franceschi C.
Published: November 2008

At present, individuals can live up to 80–120 years, a time much longer than that of our ancestors, as a consequence of the improvements in life conditions and medical care. Thus, the human immune system has to cope with a lifelong and evolutionarily unpredicted exposure to a variety of antigens, which are at the basis of profound age-related changes globally indicated as immunosenescence, a multifaceted phenomenon that increases morbidity and mortality due to infections and age-related pathologies. The major changes occurring during immunosenescence are the result of the accumulation of cellular, molecular defects and involutive phenomena (such as thymic involution) occurring concomitantly to a hyperstimulation of both innate and adaptive immunity (accumulation of expanded clones of memory and effector T cells, shrinkage of the T cell receptor repertoire, progressive activation of macrophages), and resulting in a low-grade, chronic state of inflammation defined as inflammaging. It is unknown whether inflammaging, which represents a risk factor for most age-related pathologies, is a cause or rather an effect of the aging process. In this complex scenario, the role of genetic background likely represents a fundamental variable to attain successful aging and longevity. Accordingly, centenarians seem to be equipped with gene variants that allow them to optimize the balance between pro- and anti-inflammatory molecules, and thus to minimize the effects of the lifelong exposure to environmental insults and stressors. The remarkable features of the genetics of aging and longevity are reviewed, stressing the unexpected and unusual results obtained regarding such a postreproductive type of genetics.
Melatonin and the Immune System in Aging
Authors: Cardinali Daniel P. , Esquifino Ana I. , Srinivasan Venkataramanujan , Pandi-Perumal Seithikurippu R.
Published: November 2008

Aging is associated with a decline in immune function (immunosenescence), a condition known to correlate with increased incidence of cancer as well as infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. Circulating melatonin decreases with age, and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes and macrophages. It also stimulates the production of natural killer cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from natural killer cells and T helper lymphocytes are enhanced by melatonin. Melatonin has the potential therapeutic value to enhance immune function in aged individuals.
Effect of Growth Hormone Treatment on Lymphocyte Functions in Old Male Rats
Authors: Baeza Isabel , Alvarado Carmen , Ariznavarreta Carmen , Castillo Carmen , Tresguerres Jesús A.F. , De la Fuente Mónica
Published: November 2008

Introduction: Age-related changes in the communication between the neuroendocrine and the immune system have been scarcely studied. Aging in mammals is associated with an impairment of the immune response, especially regarding lymphocyte functions. Furthermore, the endocrine system is also affected by aging, one of the most significant changes being the decrease in the secretion of several hormones such as growth hormone (GH). Objective: The aim of the present work was to study whether GH replacement therapy in old male rats could improve several lymphocyte functions. Methods: Spleen and axillary node lymphocytes from old (24 months of age) male Wistar rats were used in the present study to investigate the effect of GH (2 mg/kg daily during 10 weeks) on chemotaxis, lymphoproliferative response to the mitogen concanavalin A, interleukin 2 release and natural killer cell activity. Results: We have found that the administration of GH can reduce or even reverse the age-related changes observed in these key immune function parameters. Moreover, we have observed that the recovery of such immune functions is able to reach similar values as those exhibited by young control animals of 6 months of age. Conclusion: Considering that the immune system is a marker of health and a predictor of longevity, hormone replacement therapies with GH, by increasing the immune function and thus delaying or slowing down some aspects of the aging process, could facilitate successful aging.
Neuroinflammation Associated with Aging Sensitizes the Brain to the Effects of Infection or Stress
Authors: Sparkman Nathan L. , Johnson Rodney W.
Published: November 2008

The aging brain is characterized by a shift from the homeostatic balance of inflammatory mediators to a proinflammatory state. This increase in neuroinflammation is marked by increased numbers of activated and primed microglia, increased steady-state levels of inflammatory cytokines and decreases in anti-inflammatory molecules. These conditions sensitize the aged brain to produce an exaggerated response to the presence of an immune stimulus in the periphery or following exposure to a stressor. In the brain, proinflammatory cytokines can have profound effects on behavioral and neural processes. As the aged brain is primed to respond to inflammatory stimuli, infection or stress may produce more severe detriments in cognitive function in the aged. Typically after an immune stimulus, aged animals display prolonged sickness behaviors, increased cytokine induction and greater cognitive impairments compared to adults. Additionally, aging can also augment the central response to stressors leading to exaggerated cytokine induction and increased decrements in learning and memory. This alteration in neuroinflammation and resultant sensitization to extrinsic and intrinsic stressors can have considerable effects upon the elderly’s recovery and coping during disease and stress.
Can the Immune System Still Be Efficient in the Elderly? An Immunological and Immunoendocrine Therapeutic Perspective
Authors: Pfister Gerald , Savino Wilson
Published: November 2008

The continuous global increase in life expectancy represents a central challenge for our society and impacts public social security systems, families and individuals. One of the most striking changes that occur during normal human aging is immunosenescence, a progressive and overall diminution of immune functions that affect all cells and organs of the innate and adaptive immune system. As a hallmark of human aging, the progressive involution of the thymus leads to a disturbed balance and function of naïve, memory and effector T cells, thus promoting a latent pro-inflammatory status in the elderly. Together with chronic infections such as cytomegalovirus, that accumulate during life, this situation manifests in clinically relevant implications such as poor overall immune responses, decreased ability to control infectious disease and diminished response to vaccinations. Interestingly, this process parallels changes in the hormonal balance of aging subjects. In this review, we summarize recently published intriguing results from a very active and growing field of biomedical research and discuss some clinical consequences as well as possible ways of immune- and/or hormone-based interventions to delay or reverse immunosenescence.
Australia: Public Health Genomics
Authors: Metcalfe S.A. , Bittles A.H. , O’Leary P. , Emery J.
Published: November 2008

Australia has a multicultural society that has arisen from continuing migration. While the population is relatively small, just over 20.7 million, it is genetically diverse and is spread over a large land mass. The federal system of government is democratic, based on states and territories, and there is a socialized healthcare system, in which public and private models operate in parallel. Clinical genetics services are publicly funded by State Departments of Health, rather than by the Commonwealth Government, with the model of service provision varying from state to state. Each of these factors has important implications for the effective delivery of genetic screening programs and clinical genetic services that meet the needs of all Australians. Population genetic screening occurs throughout Australia predominantly as newborn screening programs and to identify pregnancies at risk of chromosomal and neural tube defects, while carrier screening programs are essentially ad hoc. Despite inevitable tensions between federal and state policies, there is increasing evidence of the development of national policy in a range of genetic issues, not least in newborn screening, genetic testing, and health professional education. However, further work is necessary to establish frameworks for the regulation and funding of new genetic tests across state/federal boundaries, which will be crucial to the establishment of a national approach to public health genomics policy.
Family History Questionnaires Designed for Clinical Use: A Systematic Review
Authors: Reid G.T. , Walter F.M. , Brisbane J.M. , Emery J.D.
Published: November 2008

Background: The family medical history is an important risk factor for several common chronic diseases but challenges remain in efficiently identifying individuals at increased risk. Family history questionnaires (FHQs) may have an important role in primary care as a screening tool to support tailored disease prevention. Aims: To systematically review studies reporting on the use and outcomes of FHQs in a clinical setting. Methods: Studies were identified through electronic searches of Medline, EMBASE, CINAHL, PsychInfo, and Google Scholar until December 2007. Due to the heterogeneity of the included papers, formal synthesis was not possible. We therefore developed a taxonomy based on the principal objectives and design of each study. Results: A plethora of FHQs were identified but few had been formally evaluated. Forty-four publications were reviewed. Sixteen papers met our inclusion criteria reporting 14 different FHQs. The majority of FHQs focused on 1 or more cancers. Twelve papers reported on the evaluation of a FHQ in a non-referred population, predominantly in primary care practice. Four papers reported a formal validation of a FHQ against a reference standard, demonstrating reasonable accuracy. Six further papers showed that a FHQ can be used to identify populations at increased risk of cancer, many of whom had not been previously identified. Two papers found a positive impact of using a FHQ on subsequent cancer screening, and a further 3 found no significant psychological long-term harm associated with their use. Conclusions: Despite the abundance of available FHQs, few have been formally evaluated. Several short single-cancer specific FHQs exist, but there are no simple, short generic FHQs suitable for use in primary care practice. FHQs can be used to obtain reasonably accurate family history information and to identify populations at increased disease risk. They have been shown to have a positive impact on cancer screening and are not associated with long-term psychological harm.
Australian Study on Public Knowledge of Human Genetics and Health
Authors: Molster C. , Charles T. , Samanek A. , O’Leary P.
Published: November 2008

Aims: This study was designed to obtain data on public understanding of genetic concepts in the adult population of Western Australia. It explored knowledge of genetic risk of disease, inheritance, biology, determinism, and factors that predict relatively higher genetic knowledge within the general population. Method: A cross-sectional telephone survey of 1,009 respondents. Results: Most members of the Western Australian community are aware of basic genetic concepts and the link between genes, inheritance, and risk of disease. Significantly fewer understand the biological mechanisms underlying these concepts and there was some misconception around the meaning of ‘increased genetic risk’. The odds of higher genetic knowledge (>19 out of 24 questions correct) were greater among those with 12 years or more education (OR = 3.0), those aged 18–44 years (OR = 2.3), women (OR = 2.0), those with annual household income of AUD 80,000 or more (OR = 1.8), and those who had talked with someone (OR = 1.7) or searched the internet (OR = 1.6) for information on genes and health. Conclusions: This study provides evidence of an association between social location and public knowledge of human genetic concepts related to health and disease. This is consistent with previous findings and raises questions about the acquisition of textbook genetics knowledge within socio-cultural contexts. The impact of misconceptions about genetic concepts on the uptake of preventive health behaviors requires further investigation, as does the level of genetics knowledge that is required to empower informed participation in individual and societal decisions about genetics and health.
Insulin Treatment in Intensive Care Patients
Authors: Derde Sarah , Vanhorebeek Ilse , Van den Berghe Greet
Published: November 2008

Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. In two large randomized controlled single-center studies, the maintenance of strict normoglycemia with intensive insulin therapy has been shown to reduce morbidity and mortality. The benefits were more pronounced with at least a few days of treatment. Several implementation studies confirmed that blood glucose control with intensive insulin therapy is beneficial for critically ill patients. Two studies planned as large randomized controlled trials evaluating the effect of glycemic control in adults were stopped prematurely because of protocol violation and/or increased risk of hypoglycemia. The only multicenter trial designed with sufficient statistical power to assess the impact of strict blood glucose control with intensive insulin therapy on survival of a heterogeneous adult critically ill patient population is still ongoing. While awaiting these results, the current evidence favors strict control of blood glucose levels to normoglycemia below 110 mg/dl. Avoiding glucose toxicity appears crucial to obtain the clinical benefits of this therapy, although direct insulin effects may contribute as well.
Puberty and Ovarian Function in Girls with Type 1 Diabetes Mellitus
Authors: Codner Ethel , Cassorla Fernando
Published: November 2008

Insulin is well known for its effects on carbohydrate metabolism, but this hormone also plays an important role in regulating ovarian function. Granulosa, theca and stromal ovarian cells may be affected by insulin deficiency or excess, which may be present in women with type 1 diabetes mellitus (T1D). Recent publications have shown that in spite of intensive insulin therapy, some delay in the age of thelarche, pubarche and menarche is still observed in girls with T1D. In addition, ovarian hyperandrogenism may be observed during late adolescence and an increased prevalence of hirsutism and polycystic ovarian syndrome (PCOS) has been described in adult women with T1D. These endocrine abnormalities may be related to nonphysiologic insulin replacement therapy and to hyperglycemia. This paper reviews the pubertal development and the clinical reproductive abnormalities observed in girls with type 1 diabetes mellitus, and shows that several significant clinical problems, such as pubertal delay, menstrual disturbances and hyperandrogenism which may ultimately lead to the development of PCOS in adulthood, may be observed in some of these patients.
Monogenic and Polygenic Models Detected in Steroid 21-Hydroxylase Deficiency-Related Paediatric Hyperandrogenism
Authors: Ezquieta B. , Oyarzabal M. , Barrio R. , Luzuriaga C. , Hermoso F. , Lechuga J.L. , Quinteiro S. , Rodríguez A. , Labarta J.I. , Gutierrez Macias A. , Gallego M. , Bellón J.M.
Published: November 2008

Aims: Hyperandrogenism, although mostly due to polygenic interactions, is monogenic for some enzymatic adrenal deficiencies. This study evaluates mono- and biallelic 21-hydroxylase deficiency (21OHD)-related hyperandrogenism in pediatric patients. Sensitizing and protective polymorphisms were investigated in carriers and cryptic forms of 21OHD. Methods: The study involved a monogenic analysis of CYP21A2 in patients (375 nonclassical 21OHD [NC21OHD] children; 306 hyperandrogenic 21OHD carriers, n = 306) and a polygenic association study (CAPN10-UCSNP44, PON1-108, TNFR2-M196R, IGF2-ApaI and IRS1-G972R polymorphisms) of 170 hyperandrogenic carriers plus 277 family members (control groups). The metabolic marker 17OH progesterone defined the degree of deficiency; clinical expressivity was determined by pediatric endocrinologists. Results: The group of 21OHD carriers manifesting hyperandrogenism was enriched in the CAPN-UCSNP44 rare variant in homozygosity (4.9 vs. 0.4%, NCBI data for the general population; p = 0.004). In our patients and controls, contrasting distributions were observed for this and another polymorphism, TNFR2-196R. In a recessive model, their rare variants were more frequently detected among the forms with high (p = 0.048) and low (p = 0.034) expressivity respectively. Conclusions: 21OHD-related pediatric hyperandrogenism follows monogenic and polygenic models. The opposite behaviors in terms of clinical expressivity detected for CAPN-UCSNP44 and TNFR2-M196R rare variants suggest these variants to be sensitizing and protective factors respectively in adrenal hyperandrogenism.
Three Novel Mutations in Greek Sotos Patients with Rare Clinical Manifestations
Authors: Leventopoulos George , Kitsiou-Tzeli Sophia , Psoni Stavroula , Mavrou Ariadni , Kanavakis Emmanuel , Willems Patrick , Fryssira Helen
Published: November 2008

Background: Sotos syndrome is an autosomal dominant disease characterized by tall stature, advanced bone age, typical morphological abnormalities of the face and developmental delay. It is caused by mutations in the NSD1 gene located on chromosome 5. NSD1 mutations are detected in the majority of the Sotos patients, and include intragenic NSD1 mutations and microdeletions in the 5q35 region. Cardiovascular and urogenital symptoms are more frequent in the microdeletion group. Methods: Mutation analysis was performed in 4 patients with Sotos syndrome with typical phenotypic characteristics. Results: In each of the 4 patients a NSD1 mutation was found (2 frame shifts, 1 nonsense and 1 missense mutation). Two of our patients presented dysplastic kidneys with cysts and psychosis, respectively. Conlusions: We describe 4 Greek patients with Sotos syndrome. Apart from the typical phenotypic characteristics, 2 of our patients presented rare clinical manifestations such as dysplastic kidneys and psychosis. The 3 detected mutations are novel.
Ovarian Hyperstimulation Syndrome in Newborns – A Case Presentation and Literature Review
Authors: Starzyk Jerzy , Wójcik Małgorzata , Wojtyś Joanna , Tomasik Przemysław , Mitkowska Zofia , Pietrzyk Jacek J.
Published: November 2008

Preterm ovarian hyperstimulation syndrome (POHS) is a rare condition in which immaturity of the gonadal axis is accepted as the cause. Based on our case and 8 cases from the literature, we made an attempt to specify the mechanisms underlying the syndrome and its pathognomonic signs. All POHS newborns were born between 24 and 31 weeks postconception age (WPCA) and developed vulvar, hypogastric and upper leg swelling, and ovarian follicular cyst/cysts (10–40 mm in diameter) with mildly or considerably elevated E2 concentrations (80–5,300 pmol/l) between 35 and 39 WPCA. The GnRH test, performed in 5 cases, confirmed gonadal axis activation. In our case the observed normalization of elevated gonadotropin values by 43 WPCA, accompanied by a simultaneously increasing E2 value (approximately 800 pmol/l), could correspond with the maturation of the gonadal steroid-dependent negative-feedback mechanism. The continuously increasing E2 levels after this period (maximum 1,300 pmol/l) suggest its autonomous secretion. In all the cases, including 3 neonates treated with medroxyprogesterone and surgery, the swelling resolved by 6 months. Conclusions: A pathognomonic sign of POHS is swelling which develops around 37 ± 3 WPCA, and the syndrome is only infrequently diagnosed when the swelling is profound. The direct etiologic factor here is not E2. POHS does not require therapy as long as there is no danger of cyst torsion.
Discrepancies between Preoperative Stereoencephalography Language Stimulation Mapping and Intraoperative Awake Mapping during Resection of Focal Cortical Dysplasia in Eloquent Areas
Authors: Gil Robles Santiago , Gelisse Philippe , Vergani Francesco , Moritz-Gasser Sylvie , Rigau Valerie , Coubes Philippe , Crespel Arielle , Duffau Hugues
Published: November 2008

Background/Aims: To compare the reliability of preoperative stereoencephalography (SEEG) and intraoperative electrostimulation regarding functional mapping, and to select the indication for surgery for focal cortical dysplasia (FCD) in language areas. Methods: The authors present the case of a 21-year-old, right-handed female, suffering from chronic pharmacologically resistant epilepsy since the age of 8. MRI showed a subcortical hypersignal on FLAIR and T2 sequences at the posterior end of the left superior temporal sulcus compatible with an FCD. SEEG invasive monitoring was performed to precisely identify the epileptogenic zone (EZ) and for functional language mapping. Results: The stimulation of the contacts implicated in the EZ through SEEG leads induced language disturbances, which were not reproducible. Surgery was performed under local anesthesia with awake corticosubcortical mapping. Direct intraoperative stimulation in the EZ, including FCD, did not induce language disturbances. Thus, EZ could be removed completely without any postoperative language deficit. Conclusions: The present case suggests that when language disturbances which occur during invasive SEEG functional mapping, in eloquent areas, are not reproducible, resection can be considered using intraoperative electrical mapping, without inducing permanent language impairment. This may be explained by a certain degree of plasticity and reshaping of functional areas associated with a congenital lesion and chronic epilepsy.
Recurrent Hemifacial Spasm following Minor Trauma: Report of a Case
Authors: Lega Bradley C. , Harper Richard L. , Dannenbaum Mark D. , Yoshor Daniel
Published: November 2008

Late recurrences after microvascular decompression for hemifacial spasm or trigeminal neuralgia are rare. We present an atypical case of recurrence one and a half years after successful microvascular decompression for hemifacial spasm associated with direct trauma. Implications for the management of recurrences and the judicious use of polymer adhesives such as fibrin glue are discussed.
A Time-Response Model for Analysis of Drug Transport and Blood Flow Response during Iontophoresis of Acetylcholine and Sodium Nitroprusside
Authors: Tesselaar Erik , Henricson Joakim , Jonsson Susanne , Sjöberg Folke
Published: November 2008

Background/Aims: The analysis of blood flow responses to iontophoresis of vasoactive drugs is often limited to evaluation of maximum responses. In this study, a time-response model is proposed for the blood flow responses to vasoactive drugs applied by iontophoresis. Methods: The microvascular bed is represented as a single compartment with a zero-order influx of the drugs from the electrode and a first-order clearance due to diffusion and blood flow. The blood flow response to the local drug dose is described using the Emax model. Results: The model accurately describes the blood flow responses to acetylcholine and sodium nitroprusside during a single iontophoretic current pulse. There is a significant clearance out of the microvascular bed during iontophoresis which depends on the type of drug administered. Conclusion: The model enables an accurate estimation of response parameters such as ED50 and maximum response, even if the true maximum blood flow is not obtained. The results suggest that due to clearance from the microvascular bed, the local drug dose during a single pulse of current is not linearly proportional to current strength multiplied by pulse duration.
Prospective Evaluation of Two-Stage Hepatectomy Combined with Selective Portal Vein Embolisation and Systemic Chemotherapy for Patients with Unresectable Bilobar Colorectal Liver Metastases
Authors: Pamecha V. , Nedjat-Shokouhi B. , Gurusamy K. , Glantzounis G.K. , Sharma D. , Davidson B.R.
Published: November 2008

Background: Liver resection is contraindicated in patients with multiple bilobar colorectal liver metastases because of the small liver remnant. An alternative strategy which may be curative is a two-stage hepatectomy in which the cancer is resected from one lobe and regeneration allowed prior to contralateral lobe resection. Objective: To assess the feasibility, risks, and outcomes in a prospectively applied strategy for two-stage hepatectomy. Methods: Over a 6-year period, 14 of 280 patients undergoing liver resection for colorectal liver metastases (5%) were considered for two-stage hepatectomy. Surgery was combined with chemotherapy in all (n = 14) and portal vein embolisation (PVE) selectively (n = 5). Median follow-up was 43 months. Results: Both stages were completed in 11 of 14 patients (78%). There were no deaths. Post-operative complication rates were 0% (1st hepatectomy) and 27% (2nd hepatectomy). The 5-year survival after the second hepatectomy was 50%. The mean disease-free survival was 25 ± 7.5 months. Conclusion: Two-stage hepatectomy combined with systemic chemotherapy and PVE can produce long-term survival in patients with multiple bilobar colorectal liver metastases.
Electroacupuncture and Moxibustion Attenuate the Progression of Renal Disease in 5/6 Nephrectomized Rats
Authors: Paterno Josne Carla , Freire Anaflávia Oliveira , Soares Maria Fernanda , Franco Marcello Fabiano , Schor Nestor , Teixeira Vicente Paulo Castro
Published: November 2008

Background/Aim: Chronic kidney disease is a worldwide public health problem and the prevention of its progression is still a major challenge in nephrology. Specific therapies that inhibit or attenuate this process are neither available nor satisfactory. Traditional Chinese medicine has been increasingly recognized as an effective therapeutic approach in several fields of medicine. The aim of this study was to investigate the effects of electroacupuncture (EA) and moxibustion (MO) in an experimental model of progressive renal disease in rats. Methods: Twenty-one male Wistar rats were submitted to 5/6th nephrectomy (NX) and assessed 8 weeks later and were divided into three groups: NX = only 5/6 NX, NX-AS = 5/6 NX and a 20-min EA-MO session in sham points, and NX-AM = 5/6 NX and a 20-min EA-MO session in three real acupuncture points. The treatment consisted of 16 sessions twice a week. Renal function, urine volume, serum creatinine, 24-hour proteinuria, direct and indirect blood pressure, glomerulosclerosis and tubulointerstitial fibrosis indices were assessed. Results: The NX-AM group showed a significant decrease in all investigated parameters when compared to the control groups. Conclusion: Our results suggest that EA and MO attenuated the progression of renal disease in the experimental model of 5/6 NX.
Contrasting Immunological Effects of Two Disparate Dusts – Preliminary Observations
Authors: Alenius Harri , Pakarinen Jaakko , Saris Ossian , Andersson Maria A. , Leino Marina , Sirola Kristiina , Majuri Marja-Leena , Niemelä Jari , Matikainen Sampsa , Wolff Henrik , von Hertzen Leena , Mäkelä Mika , Haahtela Tari , Salkinoja-Salonen Mirja
Published: November 2008

Background: Modern lifestyle and urbanization have been associated with a raised risk for atopic diseases whereas early and long-term exposure to a farm environment confers protection against atopic sensitization. Immunomodulatory potential and microbiological characteristics of settled airborne dust from an urban house and a barn were examined. Methods: Pulmonary inflammation was induced in mice by repeated intranasal administration of dusts. Monocyte-derived human dendritic cells (moDCs) were exposed to dusts followed by coculture with purified naïve T cells. Cytokine/chemokine mRNA and protein levels were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry. The dusts were analyzed by cloning and sequencing of 16S rRNA genes (290 sequences) for DNA, lipids, endotoxin and β-glucan, by live-dead staining, viable counting, isolation and identification of pure cultures (n = 76). Results: Repeated exposure to house dust elicited pulmonary eosinophilia in mice whereas exposure to barn dust elicited neutrophilic and lymphocytic airway inflammation. Stimulation of moDCs with urban house dust elicited expression of Th2-promoting OX40L and Jagged-1 costimulatory molecules. Dendritic cells (DCs) exposed to house dust directed naïve T cells towards Th2 responses. Exposure of DCs to barn dust elicited the development of Th1-dominated immune responses. Urban house dust contained bacterial debris almost exclusively of human commensal species (corynebacteria, streptococci) whereas barn dust comprised mainly intact, viable bacteria of high diversity and no commensal species. Conclusion: Contact to debris originating from human commensal bacteria in urban house dust elicited a Th2-type response whereas barn dust with high bacterial diversity directed the cells towards a Th1 response.
Six-Year Survival and Causes of Death among Stroke Patients in Korea
Authors: Kim Hyeon Chang , Choi Dong Phil , Ahn Song Vogue , Nam Chung Mo , Suh Il
Published: November 2008

Background: Stroke is the second leading cause of death in Korea but long-term survival of Korean stroke patients has not been studied. Thus, we examined 6-year survival and causes of death in a nationally representative inpatient sample. Methods: Between January 2000 and March 2000 in 152 sample hospitals, 4,299 first-ever stroke patients were identified and followed-up for vital status until December 2005. Mortality and mortality-related factors were evaluated by the Kaplan-Meier method and Cox proportional hazard regression analysis. Results: Ischemic stroke was the most common subtype (62.9%), followed by intracerebral hemorrhage (ICH, 21.2%), and subarachnoid hemorrhage (SAH, 6.4%). Six-year mortality was estimated at 37.1% for all strokes, 37.2% for ischemic, 41.0% for ICH, and 29.2% for SAH. Common causes of death were stroke (58.2%), malignancies (10.3%), other cardiovascular diseases (7.7%), and diabetes (6.8%). Six-year mortality was associated with old age (hazard ratio 1.70 per 10 years, 95% CI 1.62–1.78), male sex (1.29, 1.16–1.43), subtypes of ICH (1.30, 1.15–1.48) and SAH (1.43, 1.14–1.80), longer hospital admission (1.01 per 10 days, 1.00–1.03), and loss of consciousness (1.32, 1.13–1.55). Conclusions: More than 60% of Korean patients with first-ever stroke survived to 6 years. Major causes of death were stroke, cancer, cardiovascular diseases, and diabetes.
High Incidence of Respiratory Infections in ‘Nil by Mouth’ Tube-Fed Acute Ischemic Stroke Patients
Authors: Langdon P.C. , Lee A.H. , Binns C.W.
Published: November 2008

Background: Respiratory infections are common in acute stroke. Previous studies have found dysphagia is associated with respiratory infections. Of interest is whether patients who are ‘Nil by Mouth’ (NBM) and tube fed have higher risk of developing infections due to aspiration of bacteria-laden saliva or refluxed material than stroke patients who are fed orally. Methods: Prospective cohort of 330 ischemic stroke survivors were followed for 30 days and infections recorded. Results: 115 infections were treated with antibiotics; these included 51 respiratory infections. Incidence of infection in NBM tube-fed stroke patients (n = 74) was 69%, with 30 respiratory infections occurring in 74 patients who received enteral feeding after stroke. Logistic regression analysis showed tube feeding during admission was a significant risk for respiratory infection. We also saw a significant time-to-event effect with 73% (22/30) respiratory infections in tube-fed survivors diagnosed on days 2–4 after stroke, and 76% (39/51) of infections in all tube-fed survivors occurring by day 7 after stroke. Relevance to a theory of critical period of susceptibility to infection in acute stroke is discussed. Conclusions: NBM tube-fed survivors were unlikely to have aspirated anything other than saliva/secretions or reflux, yet experienced significantly higher rates of respiratory infections than survivors fed orally. Stringent oral care and measures to prevent reflux are potentially modifiable aspects of stroke management.
Active and Passive Smoking and Risk of Narcolepsy in People with HLA DQB1*0602: A Population-Based Case-Control Study
Authors: Ton Thanh G.N. , Longstreth, Jr. W.T. , Koepsell Thomas
Published: November 2008

Background: We examined the risk of narcolepsy associated with active and passive smoking among genetically susceptible individuals. Methods: We conducted a popula- tion-based case-control study in King County, Wash., USA. Between 2001 and 2005, we enrolled 67 cases through physicians and public outreach, and 95 controls through random-digit dialing. Subjects were aged between 18 and 50 years and positive for HLA DQB1*0602. All subjects were administered in-person interviews about their history of active and passive smoking. Results: We observed an increased risk of narcolepsy associated with having lived with two or more household smokers (odds ratio, OR = 5.1; 95% confidence interval, CI: 1.6, 12.1); with a grandparent or a sibling who smoked (OR = 3.0; 95% CI: 1.1, 8.3); with a non-family household member who smoked (OR = 3.7; 95% CI: 1.6, 8.6); and with an unrelated smoker for 1–2 years (OR = 3.1; 95% CI: 1.0, 9.0). The risk of narcolepsy was not associated with exposure to smoke at work or with active smoking before age 21 or before age of narcolepsy onset. Conclusion: Passive smoking may be a risk factor for narcolepsy in subjects with HLA DQB1*0602. Future studies could help clarify whether passive smoking is an important etiologic component of narcolepsy among genetically susceptible individuals.
Survival in a Neonate with Complete Urorectal Septum Malformation Sequence after Fetal Vesico-Amniotic Shunting for a Prominently Dilated Cloaca
Authors: Kanamori Yutaka , Iwanaka Tadashi , Nakahara Saori , Kawashima Hiroshi , Komura Makoto , Sugiyama Masahiko , Kamei Yoshimasa , Hyodo Hironobu , Yamaguchi Shun-ichi , Kohzuma Shiro , Taketani Yuji , Goishi Keiji , Ishiguro Akio , Tsuchida Shinya , Takamizawa Masaru , Igarashi Takashi
Published: November 2008

Complete urorectal septum malformation sequence (URSMS) is usually a lethal anomaly that is characterized by urethral obstruction, imperforate anus, ambiguous genitalia, renal agenesis or dysplasia, and mullerian duct maldevelopment. This anomaly is thought to be caused by the cessation of urorectal septum migration toward the caudal cloacal membrane. Teratogenic factors or a genetic abnormality is postulated as the etiology. To date, only 4 patients with URSMS have survived the neonatal period; however, 2 of these infants died before the age of 1 year. We report the survival in a case with complete URSMS who had moderate pulmonary hypoplasia and preserved left renal function. The cloacal remnant wasdilated more than expected because the wall of the muscle layer was torn, perhaps in early fetal life, and timely placement of vesico-amniotic shunts prevented severe pulmonary hypoplasia caused by oligohydramnios.
Identification of the Pyramidal Tract by Neuronavigation Based on Intraoperative Diffusion-Weighted Imaging Combined with Subcortical Stimulation
Authors: Ozawa N. , Muragaki Y. , Nakamura R. , Iseki H.
Published: November 2008

Background/Aims: To identify the pyramidal tract by neuronavigation based on intraoperative diffusion-weighted imaging (iDWI) combined with subcortical stimulation. Methods: Seven patients with brain tumors near the deep white matter underwent resection surgery using neuronavigation based on iDWI to visualize white matter bundles. Subcortical electrical stimulation was performed and electromyography was measured at the extremities when surgical manipulation came near the position corresponding to the depicted bundle. We validated the bundle depicted on iDWI by considering the responses to subcortical stimulation and the distance between the stimulation site and the depicted bundle. Results: Positive motor-evoked potentials were detected in 5 of 7 patients (8 stimulations) and the distance from the stimulation site to the depicted bundle was 0–4.7 mm (mean ± SD, 1.4 ± 2.1 mm). Negative (no) responses were obtained in all patients when the distance was more than 5 mm. The neuronavigation system had an average error of 0.79 ± 0.25 mm and a maximum error of 2.0 mm (n = 16). Conclusion: Neuronavigation based on iDWI combined with subcortical stimulation allowed surgeons to identify the pyramidal tract and avoid inadvertent injury. Our findings demonstrate that the white matter bundles depicted by iDWI can contain the pyramidal tract.
Validation of the National Institutes of Health Stroke Scale, Modified Rankin Scale and Barthel Index in Brazil: The Role of Cultural Adaptation and Structured Interviewing
Authors: Cincura Carolina , Pontes-Neto Octavio M. , Neville Iuri S. , Mendes Henrique F. , Menezes Daniela F. , Mariano Débora C. , Pereira Issana F. , Teixeira Larissa A. , Jesus Pedro A.P. , de Queiroz Danilo C.L. , Pereira Davidson F. , Pinto Elen , Leite João P. , Lopes Antonio A. , Oliveira-Filho Jamary
Published: November 2008

Background: We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. Methods: The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. Results: 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). Conclusion: The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates.
Handicap 5 Years after Stroke in the North East Melbourne Stroke Incidence Study
Authors: Gall Seana L. , Dewey Helen M. , Sturm Jonathan W. , Macdonell Richard A.L. , Thrift Amanda G.
Published: November 2008

Background: Handicap is rarely comprehensively examined after stroke. We examined handicap among 5-year stroke survivors from an ‘ideal’ stroke incidence study. Methods: Survivors were assessed with the London Handicap Scale [LHS, score range: 0 (greatest handicap) to 100 (least handicap)]. Multivariable regression was used to examine demographic, risk and stroke-related factors associated with handicap. Results: 351 of 441 (80%) survivors were assessed. Those assessed were more often Australian born than those not assessed (p < 0.05). The mean LHS score was 73 (SD = 21). The greatest handicap was present for physical independence and occupation/leisure items. Handicap was associated with older age, manual occupations, smoking, initial stroke severity, recurrent stroke and mood disorders. Conclusion: Reducing recurrent stroke, through better risk factor management, is likely to reduce handicap. The association between handicap and mood disorders, which are potentially modifiable, warrants further investigation.
Early Administration of Low Molecular Weight Heparin after Spontaneous Intracerebral Hemorrhage
Authors: Kiphuth Ines C. , Staykov Dimitre , Köhrmann Martin , Struffert Tobias , Richter Gregor , Bardutzky Jürgen , Kollmar Rainer , Mäurer Mathias , Schellinger Peter D. , Hilz Max-Josef , Doerfler Arnd , Schwab Stefan , Huttner Hagen B.
Published: November 2008

Background: Venous thromboembolism (VTE) is a common complication after stroke. Application of low molecular weight heparins (LMWH) has been proven to be beneficial for the prevention of VTE in ischemic stroke patients. However, there is no consensus whether and how to administer LMWH for prevention of thrombotic complications after acute spontaneous intracerebral hemorrhage (sICH), the main concern being possible hematoma growth. The objective of this study was to assess the safety of early subcutaneous LMWH in patients with sICH with respect to hemorrhage enlargement. Methods: A total of 97 patients with sICH were analyzed. LMWH (either enoxaparin-natrium or dalteparin-natrium) were initiated within 36 h after admission in all patients without clinical evidence of hemorrhage enlargement or an absence of evidence of hematoma growth on CT. Hematoma growth (significant when >33%, moderate when >20%) was assessed on follow-up CT between days 5 and 11. Results: None of the patients showed a significant hemorrhage growth. Between days 2 and 10, 2 patients experienced a moderate hematoma enlargement of 22.4 and 20.9%. None of the included patients developed a fatal lung embolism. Conclusions: Early application of subcutaneous LMWH for prevention of venous thromboembolism seems to be safe, and probably does not increase the risk of hematoma growth in patients with sICH.
Ischaemic Stroke Subtypes and Their Genetic Basis: A Comprehensive Meta-Analysis of Small and Large Vessel Stroke
Authors: Rao Rohit , Tah Vikas , Casas Juan Pablo , Hingorani Aroon , Whittaker John , Smeeth Liam , Sharma Pankaj
Published: November 2008

Background: The extent to which genetic effects on the different subtypes of small (SVD) and large vessel disease (LVD) ischaemic stroke differ remains controversial. Methods: A comprehensive genetic meta-analysis of all genes investigated by ischaemic stroke subtype was conducted. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association. Results: From the initial search of 526 manuscripts, 5 candidate genes were studied comprising 7,533 cases (LVD 4,181, SVD 3,352) and 9,835 control subjects. There was a preferential association for SVD compared to LVD with ACE/DD (SVD: OR 1.31, 95% CI 0.96–1.79; LVD: OR 1.02, 95% CI 0.82–1.26) and eNOS intron 4 ab polymorphism (SVD: OR 1.41, 95% CI 0.94–2.11; LVD: OR 1.07, 95% CI 0.77–1.49), although statistical significance was not reached. No such preference was observed for MTHFR C677T, ApoE/ε4 or PAI-1 4G/5G polymorphism. The overall number of studies and the number of subjects recruited per study in whom stroke subtype was classified were small when compared to previous published work without such phenotype classification. Conclusion: Our findings suggest that genetic effects may differ between small and large vessel subtypes, although the evidence base is small.
Increased Serum Levels of Anti-Angiogenic Factors Soluble fms-Like Tyrosine Kinase and Soluble Endoglin in Sickle Cell Disease
Authors: Landburg P.P. , Elsenga H. , Schnog J.B. , Duits A.J.
Published: November 2008

The anti-angiogenic factors soluble fms-like tyrosine kinase (sFlt)-1 and soluble endoglin (sEng) have been shown to be of importance in angiogenesis by sequestering and inhibiting vascular endothelial growth factor, placenta-like growth factor and transforming growth factor-β1 signaling. Given the potential role of angiogenesis in the pathophysiology of sickle cell disease (SCD)-related complications, serum levels of sFlt-1 and sEng were determined in SCD patients and controls. Both sFlt-1 (p = 0.002) and sEng (p = 0.004) were elevated in patients during clinically asymptomatic SCD with no further increment during painful crisis. These data suggest that sFlt-1 and sEng may be important in the regulation of angiogenesis in SCD.
Human Osteoblasts Support Hematopoietic Cell Development in vitro
Authors: Shiozawa Yusuke , Takenouchi Hisami , Taguchi Tomoko , Saito Masahiro , Katagiri Yohko U. , Okita Hajime , Shimizu Toshiaki , Yamashiro Yuichiro , Fujimoto Junichiro , Kiyokawa Nobutaka
Published: November 2008

Background/Aim: Although osteoblasts are thought to be the major component of the hematopoietic stem cell niche in the bone marrow microenvironment, the role of osteoblasts in hematopoiesis is still unclear. The ability of human osteoblasts to support early hematopoiesis was investigated. Methods and Results: Human CD34+ bone marrow cells cultured on human osteoblasts were capable of surviving without addition of cytokines and differentiated into myeloid cells with slight proliferation. The results of immunohistochemical experiments suggested activation of FAK and AKT in hematopoietic cells attached to osteoblasts. When stem cell factor, Flt3-L, and IL-3 were added to the coculture system, each cytokine distinctively enhanced proliferation and differentiation of CD34+ bone marrow cells. Conclusion: The results suggest that human osteoblasts have the ability to support hematopoietic cell development in vitro.