Showing papers by "University of Zurich published in 2004"

Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.

Abstract: Growing demand for health care, rising costs, constrained resources, and evidence of variations in clinical practice have triggered interest in measuring and improving the quality of health care delivery. For a valuable quality assessment, relevant data on outcome must be obtained in a standardized and reproducible manner to allow comparison among different centers, between different therapies and within a center over time.1–3 Objective and reliable outcome data are increasingly requested by patients and payers (government or private insurance) to assess quality and costs of health care. Moreover, health policy makers point out that the availability of comparative data on individual hospital's and physician's performance represents a powerful market force, which may contribute to limit the costs of health care while improving quality.4 Conclusive assessments of surgical procedures remain limited by the lack of consensus on how to define complications and to stratify them by severity.1,5–8 In 1992, we proposed general principles to classify complications of surgery based on a therapy-oriented, 4-level severity grading.1 Subsequently, the severity grading was refined and applied to compare the results of laparoscopic versus open cholecystectomy9 and liver transplantation.10 This classification has also been used by others11–13 and was recently suggested to serve as the basis to assess the outcome of living related liver transplantation in the United States (J. Trotter, personal communication). However, the classification system has not yet been widely used in the surgical literature. The strength of the previous classification relied on the principle of grading complications based on the therapy used to treat the complication. This approach allows identification of most complications and prevents down-rating of major negative outcomes. This is particularly important in retrospective analyses. However, we felt that modifications were necessary, particularly in grading life-threatening complications and long-term disability due to a complication. We also felt that the duration of the hospital stay can no longer be used as a criterion to grade complications. Although definitions of negative outcomes rely to a large extend on subjective “value” appraisals, the grading system must be tested in a large cohort of patients. Finally, a classification is useful only if widely accepted and applied throughout different countries and surgical cultures. Such a validation was not done with the previous classification. Therefore, the aim of the current study was 3-fold: first, to propose an improved classification of surgical complications based on our experience gained with the previous classification1; second, to test this classification in a large cohort of patients who underwent general surgery; and third, to assess the reproducibility and acceptability of the classification through an international survey.

The worldwide leaf economics spectrum

Abstract: Bringing together leaf trait data spanning 2,548 species and 175 sites we describe, for the first time at global scale, a universal spectrum of leaf economics consisting of key chemical, structural and physiological properties. The spectrum runs from quick to slow return on investments of nutrients and dry mass in leaves, and operates largely independently of growth form, plant functional type or biome. Categories along the spectrum would, in general, describe leaf economic variation at the global scale better than plant functional types, because functional types overlap substantially in their leaf traits. Overall, modulation of leaf traits and trait relationships by climate is surprisingly modest, although some striking and significant patterns can be seen. Reliable quantification of the leaf economics spectrum and its interaction with climate will prove valuable for modelling nutrient fluxes and vegetation boundaries under changing land-use and climate.

Biological, Epidemiological, and Clinical Aspects of Echinococcosis, a Zoonosis of Increasing Concern

Abstract: Echinococcosis in humans is a zoonotic infection caused by larval stages (metacestodes) of cestode species of the genus Echinococcus. Cystic echinococcosis (CE) is caused by Echinococcus granulosus, alveolar echinococcosis (AE) is caused by E. multilocularis, and polycystic forms are caused by either E. vogeli or E. oligarthrus. In untreated cases, AE has a high mortality rate. Although control is essentially feasible, CE remains a considerable health problem in many regions of the northern and southern hemispheres. AE is restricted to the northern hemisphere regions of North America and Eurasia. Recent studies have shown that E. multilocularis, the causative agent of AE, is more widely distributed than previously thought. There are also some hints of an increasing significance of polycystic forms of the disease, which are restricted to Central and South America. Various aspects of human echinococcosis are discussed in this review, including data on the infectivity of genetic variants of E. granulosus to humans, the increasing invasion of cities in Europe and Japan by red foxes, the main definitive hosts of E. multilocularis, and the first demonstration of urban cycles of the parasite. Examples of emergence or reemergence of CE are presented, and the question of potential spreading of E. multilocularis is critically assessed. Furthermore, information is presented on new and improved tools for diagnosing the infection in final hosts (dogs, foxes, and cats) by coproantigen or DNA detection and the application of molecular techniques to epidemiological studies. In the clinical field, the available methods for diagnosing human CE and AE are described and the treatment options are summarized. The development of new chemotherapeutic options for all forms of human echinococcosis remains an urgent requirement. A new option for the control of E. granulosus in the intermediate host population (mainly sheep and cattle) is vaccination. Attempts are made to reduce the prevalence of E. multilocualaris in fox populations by regular baiting with an anthelmintic (praziquantel). Recent data have shown that this control option may be used in restricted areas, for example in cities, with the aim of reducing the infection risk for humans.

The Neural Basis of Altruistic Punishment

Abstract: Many people voluntarily incur costs to punish violations of social norms. Evolutionary models and empirical evidence indicate that such altruistic punishment has been a decisive force in the evolution of human cooperation. We used H2 15O positron emission tomography to examine the neural basis for altruistic punishment of defectors in an economic exchange. Subjects could punish defection either symbolically or effectively. Symbolic punishment did not reduce the defector's economic payoff, whereas effective punishment did reduce the payoff. We scanned the subjects' brains while they learned about the defector's abuse of trust and determined the punishment. Effective punishment, as compared with symbolic punishment, activated the dorsal striatum, which has been implicated in the processing of rewards that accrue as a result of goal-directed actions. Moreover, subjects with stronger activations in the dorsal striatum were willing to incur greater costs in order to punish. Our findings support the hypothesis that people derive satisfaction from punishing norm violations and that the activation in the dorsal striatum reflects the anticipated satisfaction from punishing defectors.

Interactions between commensal intestinal bacteria and the immune system

Abstract: Although we might shudder at the thought of billions of bacteria living in our lower intestine, we are colonized by these passengers shortly after birth. However, the relationship is mostly of mutual benefit, and they shape our immune system throughout life. Here, we describe our developing understanding of the far-reaching effects that the commensal flora have on mucosal and systemic immunity and their relevance to the effects of hygiene on human disease.

Foundations of Human Sociality - Economic Experiments and Ethnographic: Evidence From Fifteen Small-Scale Societies

Abstract: 1. Introduction and Guide to the Volume 2. Overview and Synthesis 3. Measuring Social Norms and Preferences Using Experimental Games: A Guide for Social Sciences 4. Coalitional Effects on Reciprocal Fairness in the Ultimatum Game: A Case from the Ecuadorian Amazon 5. Comparative Experimental Evidence from Machiguenga, Mapuche, Huinca, and American Populations Shows Substantial Variation Among Social Groups in Bargaining and Public Goods Behavior 6. Dictators and Ultimatums in an Egalitarian Society of Hunter-Gatherers - the Hadza of Tanzania 7. Does Market Exposure Affect Economic Game Behavior? The Ultimatum Game and the Public Goods Game Among the Tsimane of Bolivia 8. Market Integration, Reciprocity, and Fairness in Rural Papua New Guinea: Results from a Two-Village Ultimatum Game Experiment 9. Ultimatum Game with an Ethnicity Manipulation: Results from Khovdiin Bulgan Sum, Mongolia 10. Kinship, Familiarity, and Trust: An Experimental Investigation 11. Community Structure, Mobility, and the Strength of Norms in an Africa Society: the Sangu of Tanzania 12. Market Integration and Fairness: Evidence from Ultimatum, Dictator, and Public Goods Experiments in East Africa 13. Economic Experiments to Examine Fairness and Cooperation among the Ache Indians of Paraguay 14. The Ultimatum Game, Fairness, and Cooperation among Big Game Hunters

Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex

Abstract: Mammalian target of rapamycin (mTOR) is a central regulator of protein synthesis whose activity is modulated by a variety of signals. Energy depletion and hypoxia result in mTOR inhibition. While energy depletion inhibits mTOR through a process involving the activation of AMP-activated protein kinase (AMPK) by LKB1 and subsequent phosphorylation of TSC2, the mechanism of mTOR inhibition by hypoxia is not known. Here we show that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the hypoxia-inducible gene REDD1/RTP801. Disruption of the TSC1/TSC2 complex through loss of TSC1 or TSC2 blocks the effects of hypoxia on mTOR, as measured by changes in the mTOR targets S6K and 4E-BP1, and results in abnormal accumulation of Hypoxia-inducible factor (HIF). In contrast to energy depletion, mTOR inhibition by hypoxia does not require AMPK or LKB1. Down-regulation of mTOR activity by hypoxia requires de novo mRNA synthesis and correlates with increased expression of the hypoxia-inducible REDD1 gene. Disruption of REDD1 abrogates the hypoxia-induced inhibition of mTOR, and REDD1 overexpression is sufficient to down-regulate S6K phosphorylation in a TSC1/TSC2-dependent manner. Inhibition of mTOR function by hypoxia is likely to be important for tumor suppression as TSC2-deficient cells maintain abnormally high levels of cell proliferation under hypoxia.

Genetic pathways to glioblastoma: a population-based study.

Abstract: We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months ( 80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.

Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart

Abstract: A novel pulse sequence scheme is presented that allows the measurement and mapping of myocardial T1 in vivo on a 1.5 Tesla MR system within a single breath-hold. Two major modifications of conventional Look-Locker (LL) imaging are introduced: 1) selective data acquisition, and 2) merging of data from multiple LL experiments into one data set. Each modified LL inversion recovery (MOLLI) study consisted of three successive LL inversion recovery (IR) experiments with different inversion times. We acquired images in late diastole using a single-shot steady-state free-precession (SSFP) technique, combined with sensitivity encoding to achieve a data acquisition window of <200 ms duration. We calculated T1 using signal intensities from regions of interest and pixel by pixel. T1 accuracy at different heart rates derived from simulated ECG signals was tested in phantoms. T1 estimates showed small systematic error for T1 values from 191 to 1196 ms. In vivo T1 mapping was performed in two healthy volunteers and in one patient with acute myocardial infarction before and after administration of Gd-DTPA. T1 values for myocardium and noncardiac structures were in good agreement with values available from the literature. The region of infarction was clearly visualized. MOLLI provides high-resolution T1 maps of human myocardium in native and post-contrast situations within a single breath-hold. Magn Reson Med 52:141–146, 2004. © 2004 Wiley-Liss, Inc.

Social Comparisons and Pro-social Behavior: Testing "Conditional Cooperation" in a Field Experiment

Abstract: People behave pro-socially in a wide variety of situations that standard economic theory is unable to explain. Social comparison is one explanation for such pro-social behavior: people contribute if others contribute or cooperate as well. This paper tests social comparison in a field experiment at the University of Zurich. Each semester every single student has to decide whether he or she wants to contribute to two Social Funds. We provided 2500 randomly selected students with information about the average behavior of the student population. Some received the information that a high percentage of the student population contributed, while others received the information that a relatively low percentage contributed. The results show that people behave pro-socially, conditional on others. The more others cooperate, the more one is inclined to do so as well. The type of person is important. We are able to fix the i?½typesi?½ by looking at revealed past behavior. Some persons seem to care more about the pro-social behavior of others, while other i?½typesi?½ are not affected by the average behavior of the reference group.

The role of income aspirations in individual happiness

Abstract: Does individual well-being depend on the absolute level of income and consumption or is it relative to one’s aspirations? In a direct empirical test, it is found that higher income aspirations reduce people’s utility, ceteris paribus. Individual data on reported satisfaction with life are used as a proxy measure for utility, and income evaluation measures are applied as proxies for people’s aspiration levels. Consistent with processes of adaptation and social comparison, income aspirations increase with people’s income as well as with the average income in the community they live in.

The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats.

Abstract: In contrast to peripheral nerves, central axons do not regenerate. Partial injuries to the spinal cord, however, are followed by functional recovery. We investigated the anatomical basis of this recovery and found that after incomplete spinal cord injury in rats, transected hindlimb corticospinal tract (CST) axons sprouted into the cervical gray matter to contact short and long propriospinal neurons (PSNs). Over 12 weeks, contacts with long PSNs that bridged the lesion were maintained, whereas contacts with short PSNs that did not bridge the lesion were lost. In turn, long PSNs arborize on lumbar motor neurons, creating a new intraspinal circuit relaying cortical input to its original spinal targets. We confirmed the functionality of this circuit by electrophysiological and behavioral testing before and after CST re-lesion. Retrograde transynaptic tracing confirmed its integrity, and revealed changes of cortical representation. Hence, after incomplete spinal cord injury, spontaneous extensive remodeling occurs, based on axonal sprout formation and removal. Such remodeling may be crucial for rehabilitation in humans.

The inner structure of ΛCDM haloes – III. Universality and asymptotic slopes

Abstract: We investigate the mass profile of cold dark matter (ΛCDM) haloes using a suite of numerical simulations spanning five decades in halo mass, from dwarf galaxies to rich galaxy clusters. These haloes typically have a few million particles within the virial radius (r200), allowing robust mass profile estimates down to radii <1 per cent of r200. Our analysis confirms the proposal of Navarro, Frenk & White (NFW) that the shape of the ΛCDM halo mass profiles differs strongly from a power law and depends little on mass. The logarithmic slope of the spherically averaged density profile, as measured by β=−d ln ρ/d ln r, decreases monotonically towards the centre and becomes shallower than isothermal (β< 2) inside a characteristic radius, r2. The fitting formula proposed by NFW provides a reasonably good approximation to the density and circular velocity profiles of individual haloes; circular velocities typically deviate from NFW best fits by <10 per cent over the radial range that is numerically well resolved. Alternatively, systematic deviations from the NFW best fits are also noticeable. Inside r2, the profile of simulated haloes becomes shallower with radius more gradually than predicted and, as a result, NFW fits tend to underestimate the dark matter density in these regions. This discrepancy has been interpreted as indicating a steeply divergent cusp with asymptotic inner slope, β0≡β(r = 0) 1.5. Our results suggest a different interpretation. We use the density and enclosed mass at our innermost resolved radii to place strong constraints on β0: density cusps as steep as r1.5 are inconsistent with most of our simulations, although β0= 1 is still consistent with our data. Our density profiles show no sign of converging to a well-defined asymptotic inner power law. We propose a simple formula that reproduces the radial dependence of the slope better than the NFW profile, and so may minimize errors when extrapolating our results inward to radii not yet reliably probed by numerical simulations.

Organic anion transporting polypeptides of the OATP/ SLC21 family : phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties

Abstract: The organic anion transporting polypeptides (rodents: Oatps, human: OATPs) form a superfamily of sodium-independent transport systems that mediate the transmembrane transport of a wide range of amphipathic endogenous and exogenous organic compounds. Since the traditional SLC21 gene classification does not permit an unequivocal and species-independent identification of genes and gene products, all Oatps/OATPs are newly classified within the OATP/SLCO superfamily and subdivided into families (≥40% amino acid sequence identity), subfamilies (≥60% amino acid sequence identity) and individual genes and gene products according to their phylogenetic relationships and chronology of identification. Implementation of this new classification and nomenclature system occurs in agreement with the HUGO Gene Nomenclature Committee (HGNC). Among 52 members of the OATP/SLCO superfamily, 36 members have been identified so far in humans, rat and mouse. The latter are clustered within 6 (out of 12) families (OATP1–OATP6) and 13 subfamilies. Oatps/OATPs represent 12 transmembrane domain proteins and contain the superfamily signature D-X-RW-(I,V)-GAWW-X-G-(F,L)-L. Although species divergence, multispecificity and wide tissue distribution are common characteristics of many Oatps/OATPs, some members of the OATP/SLCO superfamily are highly conserved during evolution, have a high substrate specificity and exhibit unique cellular expression in distinct organs. Hence, while Oatps/OATPs with broad substrate specificity appear to play an important role in the bioavailability, distribution and excretion of numerous exogenous amphipathic organic anionic compounds, Oatps/OATPs with a narrow spectrum of transport substrates may exhibit more specific physiological functions in distinct organs.

A Quantitative Map of the Circuit of Cat Primary Visual Cortex

Abstract: We developed a quantitative description of the circuits formed in cat area 17 by estimating the “weight” of the projections between different neuronal types To achieve this, we made three-dimensional reconstructions of 39 single neurons and thalamic afferents labeled with horseradish peroxidase during intracellular recordings in vivo These neurons served as representatives of the different types and provided the morphometrical data about the laminar distribution of the dendritic trees and synaptic boutons and the number of synapses formed by a given type of neuron Extensive searches of the literature provided the estimates of numbers of the different neuronal types and their distribution across the cortical layers Applying the simplification that synapses between different cell types are made in proportion to the boutons and dendrites that those cell types contribute to the neuropil in a given layer, we were able to estimate the probable source and number of synapses made between neurons in the six layers The predicted synaptic maps were quantitatively close to the estimates derived from the experimental electron microscopic studies for the case of the main sources of excitatory and inhibitory input to the spiny stellate cells, which form a major target of layer 4 afferents The map of the whole cortical circuit shows that there are very few “strong” but many “weak” excitatory projections, each of which may involve only a few percentage of the total complement of excitatory synapses of a single neuron

Pathogenesis of Apical Periodontitis and the Causes of Endodontic Failures

Abstract: Apical periodontitis is a sequel to endodontic infection and manifests itself as the host defense response to microbial challenge emanating from the root canal system. It is viewed as a dynamic encounter between microbial factors and host defenses at the interface between infected radicular pulp and periodontal ligament that results in local inflammation, resorption of hard tissues, destruction of other periapical tissues, and eventual formation of various histopathological categories of apical periodontitis, commonly referred to as periapical lesions. The treatment of apical periodontitis, as a disease of root canal infection, consists of eradicating microbes or substantially reducing the microbial load from the root canal and preventing re-infection by orthograde root filling. The treatment has a remarkably high degree of success. Nevertheless, endodontic treatment can fail. Most failures occur when treatment procedures, mostly of a technical nature, have not reached a satisfactory standard for the control and elimination of infection. Even when the highest standards and the most careful procedures are followed, failures still occur. This is because there are root canal regions that cannot be cleaned and obturated with existing equipments, materials, and techniques, and thus, infection can persist. In very rare cases, there are also factors located within the inflamed periapical tissue that can interfere with post-treatment healing of the lesion. The data on the biological causes of endodontic failures are recent and scattered in various journals. This communication is meant to provide a comprehensive overview of the etio-pathogenesis of apical periodontitis and the causes of failed endodontic treatments that can be visualized in radiographs as asymptomatic post-treatment periapical radiolucencies.

Boron nitride nanomesh.

Abstract: A highly regular mesh of hexagonal boron nitride with a 3-nanometer periodicity and a 2-nanometer hole size was formed by self-assembly on a Rh(111) single crystalline surface. Two layers of mesh cover the surface uniformly after high-temperature exposure of the clean rhodium surface to borazine (HBNH) 3 . The two layers are offset in such a way as to expose a minimum metal surface area. Hole formation is likely driven by the lattice mismatch of the film and the rhodium substrate. This regular nanostructure is thermally very stable and can serve as a template to organize molecules, as is exemplified by the decoration of the mesh by C 60 molecules.

Oxidation-responsive polymeric vesicles.

Abstract: Vesicles formed in water by synthetic macro-amphiphiles have attracted much attention as nanocontainers having properties that extend the physical and chemical limits of liposomes. We sought to develop ABA block copolymeric amphiphiles that self-assemble into unilamellar vesicles that can be further oxidatively destabilized. We selected poly(ethylene glycol) (PEG) as the hydrophilic A blocks, owing to its resistance to protein adsorption and low toxicity. As hydrophobic B blocks, we selected poly(propylene sulphide) (PPS), owing to its extreme hydrophobicity, its low glass-transition temperature, and most importantly its oxidative conversion from a hydrophobe to a hydrophile, poly(propylene sulphoxide) and ultimately poly(propylene sulphone). This is the first example of the use of oxidative conversions to destabilize such carriers. This new class of oxidation-responsive polymeric vesicles may find applications as nanocontainers in drug delivery, biosensing and biodetection.

Molecular and neuronal substrates for general anaesthetics.

Abstract: Although general anaesthesia has been of tremendous importance for the development of surgery, the underlying mechanisms by which this state is achieved are only just beginning to be understood in detail. In this review, we describe the neuronal systems that are thought to be involved in mediating clinically relevant actions of general anaesthetics, and we go on to discuss how the function of individual drug targets, in particular GABA(A)-receptor subtypes, can be revealed by genetic studies in vivo.

The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification.

Abstract: Although well established in medical terminology, the term carcinoid is no longer adequate to cover the entire morphological and biological spectrum of neoplasms of the disseminated neuroendocrine cell system. Therefore, instead of carcinoid, the WHO classification published in 2000 uses the general terms neuroendocrine tumor and neuroendocrine carcinoma. In this review a classification of gastroenteropancreatic neuroendocrine tumors based on the WHO criteria is described. We also classify and comment on the most important tumor entities. On the basis of localization and of various morphological and biological criteria, we distinguish between benign neuroendocrine tumors, tumors with uncertain malignant potential, and tumors showing low-grade and high-grade malignancy.

ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis.

Abstract: Experts discussed the definition, natural history, pathologic features, pathogenesis, electroclinical, neurophysiological, neuropsychological, structural and functional imaging findings, as well as surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). After a long-lasting consensus process the ILAE Commission Neurosurgery of epilepsy accepted the resulting conclusions as state-of-the art report on MTLE-HS. The majority of contributors considered MTLE-HS to represent a sufficient cluster of signs and symptoms to make up a syndromic diagnostic entity.

High-affinity binders selected from designed ankyrin repeat protein libraries.

Abstract: We report here the evolution of ankyrin repeat (AR) proteins in vitro for specific, high-affinity target binding. Using a consensus design strategy, we generated combinatorial libraries of AR proteins of varying repeat numbers with diversified binding surfaces. Libraries of two and three repeats, flanked by 'capping repeats,' were used in ribosome-display selections against maltose binding protein (MBP) and two eukaryotic kinases. We rapidly enriched target-specific binders with affinities in the low nanomolar range and determined the crystal structure of one of the selected AR proteins in complex with MBP at 2.3 A resolution. The interaction relies on the randomized positions of the designed AR protein and is comparable to natural, heterodimeric protein-protein interactions. Thus, our AR protein libraries are valuable sources for binding molecules and, because of the very favorable biophysical properties of the designed AR proteins, an attractive alternative to antibody libraries.

Changes in dental caries 1953-2003.

Abstract: In the first half of the 20th century, indices and methods of conducting surveys of the level of dental diseases were developed. Modern epidemiological studies began in the fifties and many reliable studies have been conducted after 1960. In the following decades, a substantial decline of caries prevalence was documented in the majority of the highly industrialized countries, with reductions of lifetime caries experience exceeding 75%. The decline comes to an end when low or very low levels of prevalence are reached. Children of low socioeconomic status and immigrants from outside Western Europe, however, generally have higher disease levels and may cause increases in caries prevalence. For this and other reasons, caries epidemiology will remain an indispensable part of dental public health.

Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey

Abstract: Background Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. Progressive accumulation of the substrate globotriaosylceramide in cells throughout the body leads to major organ failure and premature death. In response to the recent introduction of enzyme replacement therapy, the Fabry Outcome Survey (FOS) was established to pool data from European clinics on the natural history of this little-known disease and to monitor the long-term efficacy and safety of treatment. This paper presents the first analysis of the FOS database and provides essential baseline data against which the effects of enzyme replacement can be measured. Design Baseline data from a cohort of 366 patients from 11 European countries were analysed in terms of demography and clinical manifestations of Fabry disease. Results Misdiagnosis of Fabry disease is common, and the mean delay from onset of symptoms to correct diagnosis was 13·7 and 16·3 years in males and females, respectively. Although previously thought to have serious manifestations only in hemizygous men, the FOS database has confirmed that females heterozygous for Fabry disease are similarly affected. Furthermore, signs and symptoms of Fabry disease may be present from early childhood. Conclusions With the advent of enzyme replacement therapy, it is important that general practitioners and physicians in a range of specialties recognize the signs and symptoms of Fabry disease so that effective treatment can be given. Baseline data from FOS demonstrate that enzyme replacement therapy should not be restricted to hemizygous men, but should be considered for both heterozygous females and children.