bluuebunny/crossref_metadata_2025_split huggingface dataset:
Problems and Pitfalls in Community‐Based Outcomes Research
Authors: Isenberg Steven F. , Rosenfeld Richard M. 
Published: October 2005

OBJECTIVETo assess the feasibility of multisite community‐based outcomes research.DESIGNProspective observational study of variations in treating acute external otitis by otolaryngologists and primary care practitioners.SETTINGCommunity‐based independent otolaryngology practices.PARTICIPANTSPatients with external otitis treated by otolaryngologists in Project Solo, a nonprofit, grassroots organization of independent physicians united for quality, patient advocacy, and cost containment.METHODSConfidential (bar‐coded), disease‐specific outcomes questionnaires completed by patients (12 items) and by participating physicians (15 items). Response to treatment was measured with a follow‐up patient questionnaire (3 items).RESULTSNine patients were recruited from 5 of 29 enrolled otolaryngologists. Primary care practitioners were more likely to prescribe oral antimicrobials than otolaryngologists (100% vs. 44%, p = 0.03), but less likely to insert a wick in the external auditory canal (11 % vs. 78%, p = 0.02). Poor recruitment was caused by an overly long and complex survey, data collection at multiple time points, lack of time during office hours, cumbersome data collection requirements, inadequate ongoing communication, and a lack of enthusiasm for the project.CONCLUSIONSFuture efforts at implementing a multisite outcomes study will require shorter questionnaires, smoother integration of the survey process with regular office flow, simplified procedures for data exchange, frequent communication with data collection sites, and motivational programs for participating physicians and their office staff.
Sexually dimorphic patterns of space use throughout ontogeny in the spotted hyena (Crocuta crocuta)
Authors: Boydston Erin E. , Kapheim Karen M. , van Horn Russell C. , Smale Laura , Holekamp Kay E. 
Published: October 2005

AbstractObservational and telemetry data were used in a geographic information system database to document the ontogenetic development of sexually dimorphic patterns of space use among free‐living spotted hyenas Crocuta crocuta in Kenya. No measures of space use were sexually dimorphic among den‐dwelling cubs, nor were sex differences apparent among hyenas that had ceased using dens for shelter until these animals were c. 30 months of age. Significant sex differences emerged late in the third year of life, and persisted throughout the remainder of the life span; males were found farther from the geographic centre of the natal territory than were females, and the mean size of individual 95% utility distributions was larger for males than females. Most dispersal events by radio‐collared males were preceded by a series of exploratory excursions outside the natal territory. All collared males dispersed, but no collared females did so. Most dispersing males moved only one or two home ranges away at dispersal, roughly 8–10 km distant from the natal territory, before settling in a new social group.
The potential interactions between polyunsaturated fatty acids and colonic inflammatory processes
Authors: Mills S C , Windsor A C , Knight S C 
Published: October 2005

Summaryn-3 Polyunsaturated fatty acids (PUFAs) are recognized as having an anti-inflammatory effect, which is initiated and propagated via a number of mechanisms involving the cells of the immune system. These include: eicosanoid profiles, membrane fluidity and lipid rafts, signal transduction, gene expression and antigen presentation. The wide-range of mechanisms of action of n-3 PUFAs offer a number of potential therapeutic tools with which to treat inflammatory diseases. In this review we discuss the molecular, animal model and clinical evidence for manipulation of the immune profile by n-3 PUFAs with respect to inflammatory bowel disease. In addition to providing a potential therapy for inflammatory bowel disease there is also recent evidence that abnormalities in fatty acid profiles, both in the plasma phospholipid membrane and in perinodal adipose tissue, may be a key component in the multi-factorial aetiology of inflammatory bowel disease. Such abnormalities are likely to be the result of a genetic susceptibility to the changing ratios of n-3 : n-6 fatty acids in the western diet. Evidence that the fatty acid components of perinodal adipose are fuelling the pro- or anti-inflammatory bias of the immune response is also reviewed.
The costimulatory molecules CD80, CD86 and OX40L are up-regulated inAspergillus fumigatussensitized mice
Authors: Barrios C S , Johnson B D , D. Henderson J , Fink J N , Kelly K J , Kurup V P 
Published: October 2005

SummaryAspergillus fumigatus (Af) is a fungus associated with allergic bronchopulmonary aspergillosis (ABPA) and other allergic diseases. Immune responses in these diseases are due to T and B cell responses. T cell activation requires both Af-specific engagement of the T-cell-receptor as well as interaction of antigen independent costimulatory molecules including CD28-CD80/CD86 and OX40–OX40L interactions. Since these molecules and their interactions have been suggested to have a potential involvement in the pathogenesis of ABPA, we have investigated their role in a model of experimental allergic aspergillosis. BALB/c mice were primed and sensitized with Af allergens, with or without exogenous IL-4. Results showed up-regulation of both CD86 and CD80 molecules on lung B cells from Af-sensitized mice (79% CD86+ and 24% CD80+) and Af/rIL-4-treated mice (90% CD86+ and 24% CD80+) compared to normal controls (36% and 17%, respectively). Lung macrophages in Af-sensitized mice treated or not with IL-4 showed enhanced expression of these molecules. OX40L expression was also up-regulated on lung B cells and macrophages from both Af-sensitized and Af/rIL-4 exposed mice as compared to normal controls. All Af-sensitized animals showed peripheral blood eosinophilia, enhanced total serum IgE and allergen-specific IgG1 antibodies and characteristic lung inflammation. The up-regulation of CD80, CD86 and OX40L molecules on lung B cells and macrophages from Af-allergen exposed mice suggests a major role for these molecules in the amplification and persistence of immunological and inflammatory responses in ABPA.
Abrogation of IFN-γ mediated epithelial barrier disruption by serine protease inhibition
Authors: Willemsen L E M , Hoetjes J P , Van Deventer S J H , Van Tol E A F 
Published: October 2005

SummaryThe intestinal barrier function is often impaired in a variety of diseases including chronic inflammatory bowel disease. Increased intestinal permeability during episodes of active disease correlates with destruction or rearrangement of the tight junction protein complex. IFN-γ has been widely studied for its effect on barrier function and tight junction structures but its mode of action remains unclear. Since the claudin family of tight junction proteins is proposed to be involved in barrier maintenance we studied the effect of IFN-γ on claudin expression in relation to epithelial barrier function. Cycloheximide and protease inhibitors were used to study mechanisms of IFN-γ mediated barrier disruption. Intestinal epithelial cells were exposed to IFN-γ and permeability was evaluated by horse radish peroxidase (HRP) and 4 kD FITC-dextran fluxes. Occludin and claudin-1, -2, -3, and -4 tight junction protein expression was determined by Western blotting. Occludin and claudin-2 protein expression was dramatically reduced after IFN-γ exposure, which correlated with increased permeability for HRP and FITC-dextran. Interestingly, cleavage of claudin-2 was observed after incubation with IFN-γ. Serine protease inhibitor AEBSF completely abrogated IFN-γ mediated barrier disruption which was associated with preservation of claudin-2 expression. Moreover, IFN-γ induced loss of barrier integrity was found to affect claudin-2 and occludin expression through different mechanisms. Since inhibition of serine protease activity abrogates IFN-γ mediated barrier disruption this may be an important target for therapeutic intervention.
Chemokines in onchocerciasis patients after a single dose of ivermectin
Authors: Fendt J , Hamm D M , Banla M , Schulz-Key H , Wolf H , Helling-Giese G , Heuschkel C , Soboslay P T 
Published: October 2005

SummaryIvermectin treatment will effectively diminish microfilariae (Mf) of Onchocerca volvulus in the skin of patients, but therapy is associated with adverse host inflammatory responses. To investigate the association of proinflammatory chemokines with the intensity of infection and clinical adverse reactions, chemokine serum levels were measured in patients following ivermectin treatment (100 µg/kg, 150 µg/kg or 200 µg/kg) or placebo. The density of O. volvulus Mf per mg skin decreased by 85%, 97%, 97% and 90% at day 3, at month 3, month 6 and at 1 year post-ivermectin. The cutaneous T cell-attracting chemokine (CTACK/CCL27) was found highly elevated in onchocerciasis patients compared to infection-free European controls (P = 0·0004) and it did not change following ivermectin or placebo to 1 year post-therapy. The chemokine RANTES/CCL5 (regulated on activated and normally T cell-expressed) was similarly high in onchocerciasis patients and infection-free European controls; the RANTES/CCL5 levels did not change following treatment until 6 months post-therapy but were slightly elevated at 1 year post-therapy (P &lt; 0·02). In contrast, the Th2-type chemoattractants, thymus and activation regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), were activated at 3 days post-ivermectin (P &lt; 0·0001) to return to pretreatment or lower levels thereafter. The Th1-type chemoattractants, macrophage inflammatory protein (MIP)-1α/CCL3 and MIP-1β/CCL4 were low before ivermectin treatment, but following clearance of microfilariae of O. volvulus their levels increased from 6 months post-therapy onwards (for both at 12 months post-therapy, P &lt; 0·0001). The adverse reaction scores (RS) in treated patients increased significantly on day 3 (P &lt; 0·02) while it remained unchanged in those who received placebo (P = 0·22); RS interacted with the microfilarial density (P = 0·01), but not with the dose of ivermectin or with the serum levels of MIP-1α/CCL3, MIP-1β/CCL4, TARC/CCL17, MDC/CCL22 and CTACK/CCL27. Our observations suggest that following ivermectin, macrophages as well as memory Th2-type lymphocytes and B cells, attracted and activated by MDC/CCL22, TARC/CCL17 and CTACK/CCL27, may contribute to dermal immune responses and O. volvulus Mf killing and clearance. The transient changes of TARC/CCL17 and MDC/CCL22 were not associated with clinical adverse responses, and the later rise of MIP-1α/CCL3 and MIP-1β/CCL4 showed a reactivation of Type 1 immune responses associated with persistent low levels of O. volvulus microfilariae and an expiring O. volvulus infection.
The immune responses to human and microbial heat shock proteins in periodontal disease with and without coronary heart disease
Authors: Hasan A , Sadoh D , Palmer R , Foo M , Marber M , Lehner T 
Published: October 2005

SummaryThe human 60 kDa and microbial 65 kDa heat shock proteins (HSP) have been implicated in the pathogenesis of chronic periodontitis (P) and coronary heart disease (CHD). We have studied four male non-smoking cohorts of 81 subjects, matched for age. Group (a) consisted of a healthy group with minimal gingivitis (n = 18), group (b) were patients with P (n = 23), group (c) patients with CHD and minimal gingivitis (n = 20) and group (d) patients with CHD and P (n = 20). T cells separated from peripheral blood were found to be primed to both microbial HSP65 and human HSP60 but significant CD4, human leucocyte antigen (HLA) class II-restricted proliferative responses were found only with the human HSP60 in patients with P (P &lt; 0·001) and CHD without (P &lt; 0·001) or with (P &lt; 0·00001) periodontitis. Dose-dependent inhibition of T cell proliferative responses was carried out to determine the receptors involved in recognition of HSP60 and HSP65. Monoclonal antibodies to CD14 showed inhibition of T cell proliferation stimulated by both HSP60 and HSP65, consistent with the role of CD14 as a receptor for these HSPs in P and CHD. The toll-like receptor 2 (TLR-) and TLR-4 were then studied and these showed that TLR-4 was recognized by microbial HSP65, whereas TLR-2 was recognised by human HSP60 in both P and CHD. However, a dissociation was found in the HSP60 and TLR4 interaction, as TLR4 appeared to have been recognized by HSP60 in P but not in CHD. The results suggest an autoimmune or cross-reactive CD4+ class II-restricted T cell response to the human HSP60 in P and CHD. Further studies are required to determine if there is a common epitope within HSP60 that stimulates T cell proliferation in P and CHD.
Sexual medicine in the medical curriculum
Authors: WAGNER G. 
Published: October 2005

SummaryThe new field of Sexual Medicine has now changed to the primary care physician because of the new symptom‐treating pharmacological possibilities, a fact not to be foreseen 10 years ago. The future, therefore, is to create the platform for the ‘basic doctor’ to identify and correctly treat male and female sexual dysfunction on the basis of a sufficient knowledge (obtained through formalized, pre‐graduate education) within the field of Sexual Medicine. All this will need positive support and good strategies, as well as evidence‐based new knowledge created by endocrinology, gynaecology, andrology, genetics, neurology, angiology, but also psychology, sociology, anthropology and related disciplines to help the medical clinician to fulfil his Hippocratic Oath: to assist the individual who needs help – in sexual dilemmas as well.
Why humans need type 5 phosphodiesterase inhibitors
Authors: CELLERINO A. , JANNINI E. A. 
Published: October 2005

SummaryErectile dysfunction (ED) is a widespread medical condition affecting millions of males at any age and requiring medical treatment. ED may simply reflect a limit of human physiology, yet ED equates to genetic death and the high prevalence of ED is a clear evolutionary paradox. Why is a condition which totally blocks reproduction so widespread? Epidemiology shows that impotence is a common symptom of almost all major diseases and male reproductive physiology is sensitive to general health and to environmental, psychological, and physical stressors. Moreover, erectile dysfunction is a predictor of myocardial infarction and stroke. Briefly, efficient erection is a marker of good health and good health prognosis. In the animal kingdom, mate choice is often based on extravagant and cumbersome physical traits (such as the peacock's tail). These traits, that are necessary for gene propagation, are at the same time efficient handicaps which reduce the survival of the carrier. What animal studies show, is that these handicaps can function as honest indicators of the individual's fitness. In other words, their expression is condition‐dependent and only individuals with high phenotypic quality present the trait. By mating with males which express the trait, females indirectly select for individuals of superior fitness which will be inherited by the offspring. Erection is very clearly a condition‐dependent trait in the human species. We suggest that the fragility of male sexual physiology is a sexually selected handicap which hampers the reproduction of individuals with lower phenotypic quality.
Central hormonal regulation and dimorphism of arousal
Authors: BENVENGA S. 
Published: October 2005

SummaryFrom studies in animals, we have learned that differences in sexual behaviour between males and females reflect anatomical and biochemical differences between the male and female brain. A masculine behaviour (and therefore a masculine brain) results from the biological effect on the developing brain exerted by testosterone, which is secreted by the gonads and aromatized into oestrogens in the brain. However, congenital disorders of the androgen as well as oestrogen signalling in human males have failed to show any appreciable derangement in sexual behaviour. Based on other evidence in animals, sexual differences in brain (and behaviour) are not hormonally triggered but genetically determined. This other theory states that sexual behaviour is determined by the chromosomal sex existing in cells, including brain cells. A number of excitatory and inhibitory signals modulate the activity of certain brain structures. Scientists have begun to test some of these chemicals or their synthetic analogues/antagonists in humans.
Vascular aetiology of erectile dysfunction
Authors: FRANCAVILLA S. , BOCCHIO M. , PELLICCIONE F. , NECOZIONE S. , FRANCAVILLA F. 
Published: October 2005

SummaryErectile dysfunction (ED) shares the same vascular risk factors (VRFs) with coronary arteries disease (CAD). A reduced biological activity of endothelium‐derived nitric oxide links human atherosclerosis to ED and underscores the role of an altered endothelium in the pathogenesis of both conditions. ED is associated to a systemic endothelial cell activation/dysfunction independent from VRFs or from a diffuse vascular damage, indicating that ED is a marker of an early systemic endothelial damage, a relevant determinant of atherosclerosis. A diffuse vascular damage of carotid arteries indicative of pre‐clinical atherosclerosis is significantly associated to an increased risk of severe ED in men with VRFs but without clinical atherosclerosis and ED was the most efficient predictor of angiographically verified silent CAD among different VRFs in uncomplicated type 2 diabetes. In conclusion, ED may be the only clinical correlate of a diffuse, unrecognized vascular damage that is associated to a documented future risk of acute vascular events. Searching ED might be of relevance in men with VRFs but no other clinical atherosclerosis to identify patients that should aggressively reduce their VRFs while treating ED.
Diagnosing erectile dysfunction: instruments for endocrine diagnosis
Authors: LOMBARDO F. , GANDINI L. , JANNINI E. A. , SGRÒ P. , GILIO B. , TOSELLI L. , DONDERO F. , LENZI A. 
Published: October 2005

SummaryEndocrine factors represent an important and potentially treatable cause of sexual dysfunction. The availability of a correct endocrinological diagnosis allows correct identification of most cases of sexual dysfunction in which the endocrine apparatus is involved. Not only the most frequent causes of endocrine sexual dysfunction, such as hypogonadism and hyperprolactinaemia, but almost all extra‐gonadal endocrinopathies (hyper‐and hypothyroidism, hyper‐ and hypocortisolism, steroidal secreting tumours, etc.) may have importance to a greater or lesser extent in sexual function. It is, therefore, necessary that the diagnostic process for sexual dysfunctions of an endocrine nature be as integrated and wide as possible, especially as such pathologies are normally extremely responsive to medical or surgical therapy.
Diagnosing Erectile Dysfunction: flow‐chart
Authors: FORESTA C. , CARETTA N. , PALEGO P. , SELICE R. , GAROLLA A. , FERLIN A. 
Published: October 2005

SummaryErectile dysfunction (ED) has been defined by the National Institute of Health (NIH) as the inability to achieve and/or maintain an erection for a satisfactory sexual intercourse. Discordant data have been reported on ED epidemiology with prevalence ranging from 12% to 52%. A recent study reported an ED prevalence of 12.8% in Italy. ED is a symptom, sometimes the first, of different internal diseases. ED can mark the point where evaluation and prevention of important diseases (such as diabetes, arterial hypertension, atherosclerosis) hitherto unknown by the patients, can begin. The andrologist's cultural baggage must include the ability to identify the pathology that can determine ED and the capacity to programme a specific diagnostic workup.
The therapeutic dilemma: how to use psychotherapy
Authors: GIOMMI R. , CORONA G. , MAGGI M. 
Published: October 2005

SummaryOrganic, marital and intrapsychic disturbances mutually interact in the pathogenesis of erectile dysfunction (ED). Sexual psychotherapy (SP) should be considered a useful chance on all occasions. When non‐organic causes are predominant, SP could help in solving the problem. Conversely, when ED is mainly a symptom of organic diseases, SP should be considered as an important support, reducing the net contribution of marital and/or intrapsychic components and improving responsiveness and compliance to medical treatments. A correct diagnosis is a crucial step in the evaluation of patients reporting ED, in order to quantify the contribution of different pathogenetic factors. Structured Interview on Erectile Dysfunction (SIEDY©) is a useful instrument for the first screening of ED patients, providing scores for organic, marital and intrapsychic components. Other instruments, such as body paint or sexuality tree, might also be used to further analyse the problem and to choose the most effective SP intervention for the patient himself or for the couple. In our view, medical and psychosexual therapies are not indeed two distinct therapeutic entities to be used in different clinical settings, but are two important tools to be simultaneously considered (and often simultaneously employed) to fully rescue the sexual satisfaction of the couple.
Correlation between ejaculatory and erectile dysfunction
Authors: JANNINI E. A. , LOMBARDO F. , LENZI A. 
Published: October 2005

SummaryPremature ejaculation (PE) and erectile dysfunction (ED) are different sexological issues. However, they have many little‐known links. PE is the most common male sexual dysfunction, but ED is undoubtedly the most common reason that medical help is sought. As a consequence, PE is largely under‐diagnosed and under‐treated, while ED has received great scientific and clinical attention in recent years. There are plenty of reasons for this: (i) PE is classically considered as psychogenic in nature; (ii) it is traditionally treated with behavioural psychotherapies; (iii) clear and accepted clinical definition(s) are lacking; (iv) the aetiologies are largely unknown; (v) the pathogenesis is still obscure – there is a lack of awareness and acknowledgement of PE as a symptom of medical disease; (vi) lacking a medical presence in the field and requests for help from patients are low. Finally, erectile dysfunctions (ED) and ejaculatory dysfunctions frequently overlap. The aim of this review article is to propose a new taxonomy of PE, which considers ED as an important factor of PE and vice versa.
The cdc25 phosphatase is essential for the G2/M phase transition in the basidiomycete yeast Ustilago maydis
Authors: Sgarlata Cecilia , Pérez‐Martín José 
Published: October 2005

SummaryCdc25‐related phosphatases reverse the inhibitory phosphorylation of mitotic Cyclin‐dependent kinases mediated by Wee1‐related kinases, thereby promoting entry into mitosis. In the fission yeast, Schizosaccharomyces pombe, Cdc25 is required for entry into mitosis, while in the budding yeast Saccharomyces cerevisiae, Mih1 (the homologue of Cdc25) is not required for entry into mitosis or for viability. As these differences were linked to the different cell division and growth mechanism of these species, we sought to analyse the roles of Cdc25 in Ustilago maydis, which as S. cerevisiae divides by budding, but relies in a polar growth. This basidiomycete yeast is perfectly suited to analyse the relationships between cell cycle and morphogenesis. We show that U. maydis contains a single Cdc25‐related protein, which is essential for growth. Loss of Cdc25 function results in a specific G2 arrest that correlated with high level of Tyr15 phosphorylation of Cdk1. Moreover, we show genetic interactions of cdc25 with wee1 and clb2 that support the notion that in U. maydis Cdc25 counteracts the Wee1‐mediated inhibitory phosphorylation of Cdk1–Clb2 complex. Our results supports a model in which inhibitory phosphorylation of Cdk1 is a primary mechanism operating at G2/M transition in this fungus.