Search

Background Alpha-mannosidosis is caused by mutations in MAN2B1, leading to loss of lysosomal alpha-mannosidase activity. Symptoms include intellectual disabilities, hearing impairment, motor function disturbances, facial coarsening and musculoskeletal abnormalities. Methods To study the genotype-phenotype relationship for alpha-mannosidosis 66 patients were included. Based on the predicted effect of the mutations and the subcellular localisation of mutant MAN2B1 in cultured cells, the patients were divided into three subgroups. Clinical and biochemical data were collected. Correlation analyses between each of the three subgroups of genotype/subcellular localisation and the clinical and biochemical data were done to investigate the potential relationship between genotype and phenotype in alpha-mannosidosis. Statistical analyses were performed using the SPSS software. Analyses of covariance were performed to describe the genotype-phenotype correlations. The phenotype parameters were modelled by the mutation group and age as a covariate. P values of

A deficiency of the lysosomal enzyme ceramidase leads to accumulation of the sphingolipid ceramide in several organs such as skin, liver, brain and other tissues, resulting in a broad spectrum of clinical manifestations. The most common form, called Farber lipogranulomatosis, is characterized by subcutaneous skin nodules and a progressive hoarseness, in many cases also the central nervous system is affected. A lethal hydrops fetalis represents the most severe form. A ceramidase deficiency was also found in a few patients in whom neurological symptoms such as spinal muscular atrophy and myoclonus epilepsy dominated the clinical picture. In the ceramidase gene, which has been mapped to chromosome 8 and contains 14 exons, more than 20 different mutations have been identified. Bone marrow transplantation is the only available treatment. Gene therapy may become available in the future.

Fabry Disease (FD) is a rare X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A (alpha-GAL) enzyme activity. Neutral glycosphingolipides (esp. Gb3) accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. Cerebral manifestations that might be mainly due to progressive cerebrovascular dysfunction, are one major and often life-threatening burden of the disease. We reviewed the present literature concerning brain structural alterations in FD and discuss the possibly relevant underlying pathophysiological aspects of these disturbances. Cerebrovascular events (TIA, stroke) occur in FD at a rather early age. In female FD patients who were considered to be less affected "carriers" for a long time, the prevalence of cerebrovascular events seems to be at last as high as in male patients. In structural imaging white matter lesions (WML) can be found frequently even in young FD patients. In a recent study clinically equally affected men and women with FD showed a comparable severity of WML load. Different pathophysiological aspects of cerebral angiopathy and WML development are discussed against the background of current concepts (e. g. accumulation of Gb3 in vascular endothelium with consecutive cell proliferation and luminal stenosis, acceleration of focal intravasal pressure and disturbances of vascular auto-regulation). Pathological increase of pulvinar signal in T1-weighted MRI has also been described in FD. This finding was assumed to be caused by calcification as a consequence of disturbed local circulation. To enhance our knowledge about the relevant neurobiological processes the authors propose a more sensitive and early detection of brain structural changes in FD. New brain structural MRI methods such as diffusion-tensor imaging could provide a pattern of ultrastructural changes even in young patients without visible WML. This strategy could be as well useful for quantification of possible effects of the enzyme replacement therapy on brain structural alterations in FD. Based on recent data a systematic FD-screening by measuring Gb3 in urine of young patients with cryptogenic stroke should be discussed. Basically in such cases FD should be clinically considered.

CONTEXT. Fabry disease is an X-linked multisystem disorder. Enzyme-replacement therapy in adults has limited efficacy in treating major sequelae of advanced Fabry disease, such as kidney failure or stroke. This prompted a study of the safety and efficacy of enzyme replacement at an earlier stage of Fabry disease. OBJECTIVES. Our purpose with this work was to evaluate safety and to explore efficacy of enzyme treatment with agalsidase alfa in pediatric patients with Fabry disease. METHODS. We conducted a 6-month open-label study at 3 tertiary care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8 (range: 6.5–18) years, to examine safety parameters, including infusion reactions and antiagalsidase alfa antibodies. RESULTS. Agalsidase alfa was well tolerated, and all of the patients completed the study. Six boys and 1 girl had mild-to-moderate infusion reactions. One boy developed transient immunoglobulin G antibodies against agalsidase alfa. The boys showed a significant reduction in plasma globotriaosylceramide on treatment. Mean estimated glomerular filtration rate, cardiac structure, and function were normal and did not change over 26 weeks. Heart rate variability, as determined by 2-hour ambulatory monitoring, was decreased in the boys compared with the girls at baseline. All indices of heart rate variability improved significantly in the boys. Three patients with anhidrosis, as determined by quantitative sudomotor axon reflex testing, developed sweating. Six of 11 patients could reduce or cease their use of antineuropathic analgesics. CONCLUSIONS. Enzyme replacement with agalsidase alfa was safe in this study. The exploratory efficacy analysis documented increased clearance of globotriaosylceramide and improvement of autonomic function. Prospective long-term studies are needed to assess whether enzyme replacement initiated early in patients with Fabry disease is able to prevent major organ failure in adulthood.

Background Fabry disease is a rare X-linked disease arising from deficiency of α-galactosidase A. It results in early death related to renal, cardiac, and cerebrovascular disease, which are also important outcomes in patients with elevated blood pressure (BP). The prevalence of uncontrolled hypertension, as well as the effect of enzyme replacement therapy on BP, in patients with Fabry disease is unknown. Methods We examined uncontrolled hypertension (systolic BP [SBP] ≥130 mm Hg or diastolic BP [DBP] ≥80 mm Hg) among 391 patients with Fabry disease who were participating in the Fabry Outcome Survey (FOS). Results Uncontrolled hypertension was present in 57% of men and 47% of women. In patients with chronic kidney disease (CKD) stage 1 (n100), median SBP was 120 mm Hg and median DBP was 74 mm Hg. In patients with CKD stage 2 (n172), median SBP was 125 mm Hg and median DBP was 75 mm Hg. In patients with CKD stage 3 (n63), median SBP was 130 mm Hg and median DBP was 75 mm Hg. There was a significant decrease in both SBP and DBP during a 2-year course of enzyme replacement therapy. Conclusions This study revealed a high prevalence of uncontrolled hypertension among patients with Fabry disease. Thus there is a need to improve BP control and renoprotection in patients with Fabry disease.

Purpose: To evaluate the safety and efficacy of recombinant human iduronate-2-sulfatase (idursulfase) in the treatment of mucopolysaccharidosis II. Methods: Ninety-six mucopolysaccharidosis II patients between 5 and 31 years of age were enrolled in a double-blind, placebo-controlled trial. Patients were randomized to placebo infusions, weekly idursulfase (0.5 mg/kg) infusions or every-other-week infusions of idursulfase (0.5 mg/kg). Efficacy was evaluated using a composite endpoint consisting of distance walked in 6 minutes and the percentage of predicted forced vital capacity based on the sum of the ranks of change from baseline. Results: Patients in the weekly and every-other-week idursulfase groups exhibited significant improvement in the composite endpoint compared to placebo (P = 0.0049 for weekly and P = 0.0416 for every-other-week) after one year. The weekly dosing group experienced a 37-m increase in the 6-minute-walk distance (P = 0.013), a 2.7% increase in percentage of predicted forced vital capacity (P = 0.065), and a 160 mL increase in absolute forced vital capacity (P = 0.001) compared to placebo group at 53 weeks. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 46.9% of patients during the study. Conclusion: This study supports the use of weekly infusions of idursulfase in the treatment of mucopolysaccharidosis II.

DFT calculations were performed on covalently linked porphyrin–quinone and porphyrin–hydroquinone dyads, and quinhydrone (1:1 quinone–hydroquinone) paired self-assembled supramolecular complexes. The frontier HOMO's and LUMO's of the B3LYP/3-21G(*) and PBEPBE/6-31G(d) optimized structures in the ground state were utilized to probe the site of electron transfer (porphyrin or quinone centered redox reactions) and the results were compared to the experimentally determined site of electron transfer. These studies revealed good agreement between the experimental results and computational predictions. The computed HOMO–LUMO energy gap also followed the trends of the electrochemical results. In the optimized structure of quinhydrone supramolecules, the quinone–hydroquinone entities were stacked on one another with an inter-planar distance of ∼3.1 A. The calculated O–H–O distances suggested the presence of hydrogen bonds. The prediction of the structure and site of electron transfer suggests the usefulness of DFT calculations for probing the self-assembly process and redox behavior of structurally complex molecular and supramolecular systems. The B3LYP/3-21G(*) calculated association energy (the energy of the quinhydrone complex relative to the sum of the energies of the individual entities) for the quinhydrone formation was found to range between −7 and −15 kcal/mol, suggesting quinhydrone as a viable self-assembly mechanism to form supramolecular complexes. The B3LYP/3-21G(*) results were further improved by the PBEPBE/6-31G* method with solvation. Calculations performed at larger basis sets including 6-31G*, 6-31+G*, 6-31++G*, 6-311G*, 6-311G (d,p), and 6-311G (2df, dp) either at HF, BLYP, B3LYP, B3PW91, PBEPBE and MPW1PW91 methods also predicted negative association energies for the simple quinone:hydroquinone (quinhydrone) formation, with smaller association energies at the higher basis sets presumably due to reduced BSSE. Adding the basis set superposition error (BSSE), computed by counterpoise method, over-corrected the B3LYP/3-21G(*) association energy, but adding 50% of BSSE converged rapidly to the large basis set result. Larger association energies were obtained for the porphyrin–quinhydrone assemblies using PBEPBE/6-31G* calculations, presumably due to larger intermolecular ‘dispersion’ forces predicted with the PBEPBE method.

Fabry disease is a rare lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α-galactosidase A. The resultant storage of undegraded glycolipids leads to the progressive development of potentially life-threatening manifestations affecting multiple organ systems in the body. This paper describes the development of the Mainz Severity Score Index (MSSI), a scoring system for patients with Fabry disease. Conclusion: The MSSI score has been proven to be representative in patients with 'classic' Fabry disease and may be useful for monitoring clinical improvement in patients receiving enzyme replacement therapy.

Since enzyme-replacement therapy has been successfully introduced for patients with Gaucher disease, Fabry disease and mucopolysaccharidosis Type I, the principle of this treatment has also been taken into consideration for individuals who are affected by mucopolysaccharidosis Type VI (Maroteaux–Lamy disease), a rare lysosomal storage disorder with multiple organ and tissue involvement. After enzyme-replacement therapy with recombinant human arylsulfatase B in a feline model of mucopolysaccharidosis VI showed a reduction in storage vacuoles in Kupffer cells and connective tissue, clinical trials were intitiated. A Phase I/II trial showed that regular infusions of recombinant arylsulfatase B were able to reduce urinary glycosaminoglycan excretion. In all patients, general endurance and shoulder range of motion improved. These results were confirmed by a following open-label Phase II study with ten patients who had more rapidly advanced disease. After a Phase III (double-blind, placebo-controlled) study had demonstrated the clinical efficacy of weekly infusion of recombinant human arylsulfatase B, this enzyme preparation was approved by the US Food and Drug Administration for the treatment of patients with mucopolysaccharidosis Type VI. The efficacy and safety of the enzyme preparation is discussed in this review.

Introduction: The purpose of this study was to evaluate the perception of facial attractiveness in profile digital photographs that were incrementally altered to produce different combinations of mandibular anteroposterior positions and lower anterior facial heights. The specific aims were to determine whether there is concordance between providers and consumers in their perceptions of facial attractiveness, and to evaluate whether interactions of the anteroposterior and vertical dimensions and the magnitude of these interactions influence perception of facial attractiveness. Methods: Profile digital photographs and cephalograms of 3 men and 3 women were used. The position of the jaw was altered incrementally with Dolphin imaging equipment (Dolphin Imaging and Management, Chatsworth, Calif), and booklets were created. One hundred raters (50 laypersons, 25 oral surgeons, 25 orthodontists) scored the profiles on a visual analog scale. All images were duplicated to test intrarater reliability. Factorial ANOVA with repeated measures and the Tukey-Kramer post-hoc test for multiple comparisons were used to test for differences in facial attractiveness. The level of significance was set at .05 ( P = .05) for all analyses. Results: Intrarater reliability was good (ICC = 0.71), and general concordance was found between providers and consumers in their perceptions of facial attractiveness. Interactions of the anteroposterior and vertical dimensions and the magnitude of change in each dimension influence the perception of facial attractiveness. Conclusions: The results suggest that preferences of facial attractiveness by laypersons, orthodontists, and oral surgeons in central Ohio are generally in agreement. This information might assist clinicians in treatment planning and making recommendations.

Introduction: This purpose of this study was to examine the effects of a structured telephone call after orthodontic appliance placement on self-reported pain and anxiety. Methods: One hundred-fifty orthodontic patients were randomly assigned to 1 of 3 groups and matched for age, sex, and ethnicity. The subjects completed baseline questionnaires to assess their levels of pain (on a 100-mm visual analog scale) and anxiety (Spielberger’s State-Trait Anxiety Inventory) before orthodontic treatment. After the initial archwires were placed, all subjects completed the pain questionnaire and state-anxiety inventory at the same time daily for 1 week. One group also received a structured telephone call demonstrating care and reassurance; the second group received an attention-only telephone call, thanking them for participating in the study; the third group served as a control. Results: Although both telephone groups reported significantly less pain ( P = .005) and state-anxiety ( P = .033) than the control group, there was no difference between the 2 telephone groups ( P > .12 for pain; P > .81 for state-anxiety). Conclusions: A telephone call from a health-care provider reduced patients’ self-reported pain and anxiety; the content of the telephone call was not important.

The approaches to the skeletal component of malocclusion and the timing of treatment are reviewed based on changing concepts in craniofacial growth and evidence-based results from clinical trials and meta-analysis. Timing of treatment has traditionally been considered “early” versus “late mixed” or “preadolescent dentition.” The rationales are based on modification of growth during the greatest somatic and facial growth period or the option of camouflage and orthognathic surgery depending on the severity of the malocclusion. To illustrate controversies in the timing of treatment a retrospective study is reported with data from three approaches: (1) growth modification, (2) camouflage, and (3) orthognathic surgery in Class II skeletal correction. Inclusion criteria for all 3 groups included overjet of 6 mm or greater and Class II molar relationships. Results demonstrated positive skeletal changes for the growth modification group and orthognathic surgery group. Upper incisor retraction was common in all treatment groups, but compensation in the camouflage group resulted in the upper incisors being in a significantly retrusive position. Growth modification treatment resulted in lower incisor compensation. In the orthognathic surgery group, upper incisor retraction occurred pre and post surgery and lower incisor decompensation occurred post surgery. For all treatments incisor axial inclination changes and bodily movement played an important part in treatment outcome. The timing of treatment interventions was influenced by the severity of the malocclusion and the age and maturation of the patient at the time the patient presented for treatment.

Fabry Disease (FD) is an X-linked lysosomal storage disorder (prevalence about 1 : 100 000) caused by a genetic defect associated with a lack of alpha-galactosidase A (alpha-GAL) enzyme activity. As a consequence, neutral glycosphingolipides can not be cleaved and metabolized, and accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. The most prominent symptoms comprise pain attacks and acroparesthesia, angiokeratoma, corneal opacity, renal and cardiac dysfunction, hypo- and anhidrosis, gastrointestinal symptoms, and cerebrovascular dysfunction with vertigo, headache, and cerebral ischemia. Characteristic symptoms of FD can occur in male and female patients with the same prevalence, while females with FD seem to be less severely affected. The course of untreated illness is progressive with considerable interindividual variability. Since 2001 two enzyme replacement therapies are approved which can possibly stop the disease progress and alleviate symptoms. The very few reports and clinical observations have shown that a very high proportion of FD patients develop neuropsychiatric symptoms. However, accurate data are lacking. Although the pathophysiologic mechanisms are quite unknown, it is surmised that sphingolipid deposits in the endothelium of small cerebral vessels lead to regional cerebral ischemia accompanied by neuropsychiatric symptoms and deficits. Furthermore, patients with FD are chronically distressed by pain attacks and additional somatic and psychological impairment. Frequently, pain attacks are triggered by psychosocial stress. The high interindividual variability can, thus, also be interpreted on the basis of existing stress and coping models. The present paper will review the presently available psychiatric and neuropsychological findings in FD and will discuss difficulties associated with classification and differential diagnosis of psychiatric disorders occurring in patients with FD.

Anemia is a new complication in Fabry disease: Data from the Fabry Outcome Survey.BackgroundThe prevalence and causes of anemia among patients with Fabry disease are unknown.MethodsIn a cross-sectional study we examined hemoglobin concentrations of patients with Fabry disease using a large international database, the Fabry Outcome Survey (FOS), and analyzed the association of renal function, heart failure, gastrointestinal symptoms, and inflammation, with anemia (hemoglobin 90 mL/min/1.73 m2] and anemia, heart failure [New York Heart Association (NYHA) class II to IV] and/or elevated C-reactive protein (CRP) levels were documented in 82% of patients. Up to 67% of patients with decreased estimated GFR presented with anemia. There was also a trend for lower hemoglobin levels among patients with signs of inflammation (defined by an elevated CRP level). We observed no association of the presence of gastrointestinal symptoms with anemia. Analyses in 53 patients receiving enzyme replacement therapy for up to 2 years, suggest no effect on anemia.ConclusionThe results of this study point to a high prevalence of anemia among patients with Fabry disease that is in most instances related to impaired renal function, heart failure, and inflammation. This finding may be of clinical relevance, because anemia is a major risk factor for patients with kidney disease, heart failure, or stroke, which are important manifestations of Fabry disease.

A cross-sectional survey in individuals affected with the lysosomal storage disease Mucopolysaccharidosis VI (MPS VI) was conducted to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of the disease. The survey evaluated 121 bona fide MPS VI-affected individuals over the age of 4 years from 15 countries across the Americas, Europe, and Australasia representing greater than 10% of the estimated world prevalence of the disease. A medical history, complete physical exam, urinary GAG determination, and assessment of several clinical measures related to physical endurance, pulmonary function, joint range of motion, strength, and quality of life were completed for each participant. Although a wide variation in clinical presentation was observed, several general findings were obtained reflecting progression of the disease. Impaired physical endurance, as measured by the distance achieved in a 6-min walk, could be demonstrated across all age groups of MPS VI-affected individuals. High urinary GAG values (>200 mug/mg creatinine) were associated with an accelerated clinical course comprised of age-adjusted short stature and low body weight, impaired endurance, compromised pulmonary function, and reduced joint range of motion. An unexpected result was the predominance of urinary GAG values

Angiomatous lesions are common in infants and children. Hemangioendotheliomas (HE) represent one type of these lesions. Endothelial cell proliferation and the development of vascular/blood cell-filled spaces are inherent in the growth of HE. Therefore, understanding mechanisms that regulate the proliferation of these lesions should provide key insight into mechanisms regulating angiogenesis. A murine model was used to test the significance of monocyte chemoattractant protein (MCP)-1 in HE proliferation. EOMA cells, a cell line derived from a spontaneously arising murine HE, generate these lesions with 100% efficiency when injected subcutaneously into syngeneic mice. MCP-1 produced by EOMA cells recruit macrophages, which were shown to induce angiogenic behavior in EOMA cells by stimulating transwell migration and inducing sprout formation on type I collagen gels. When EOMA cells were injected into MCP-1−/−mice, only 50% of the mice developed tumors, presumably because the low levels of MCP-1 expressed by the injected EOMA cells were enough to overcome any host deficits of this chemokine. When EOMA cells were coinjected with a neutralizing antibody to MCP-1, tumors failed to develop in any of the treated mice, including syngeneic 129P3, C57Bl/6 (wild type), and MCP-1−/−. These results present the first evidence that MCP-1 is required for HE proliferation and may promote the growth of these lesions by stimulating angiogenic behavior of endothelial cells. This study has produced the first in vivo evidence of a complete response for any neoplasm, specifically a vascular proliferative lesion, to anti-MCP-1 therapy in animals with intact immune systems.

The purpose of this study was to investigate the glass transition temperatures (T(g)) of representative elastomeric chain products (plastic modules) in the as-received condition and after orthodontic use to determine differences between brands and pigments. Values of T(g) were determined by differential scanning calorimetry. Products were obtained from 3 manufacturers: Rocky Mountain Orthodontics (RMO, Denver, Colo), Ormco (Glendora, Calif), and GH (Greenwood, Ind). Three colors (gray, red, and purple) were selected for each brand-pigment combination to evaluate the as-received products, and test specimens for each brand-pigment combination from the same batches were placed in patients' mouths for 4 weeks to evaluate the products after clinical use (sample size of 7 specimens for both groups of experiments). Results were analyzed statistically by multiple nonparametric Mann-Whitney tests. A post hoc step-down Bonferroni analysis followed, to examine differences in T(g) due to pigmentation within brands and differences due to brands within each pigmentation category. For the as-received products, the RMO modules had mean T(g) ranging from -24 degrees C to -21 degrees C, whereas the Ormco and GH modules had significantly lower mean T(g), ranging from -46 degrees C to -39 degrees C, indicating substantial compositional or polymer structural differences compared with the RMO modules. After clinical use, the RMO products had mean T(g) ranging from -31 degrees C to -25 degrees C, whereas the Ormco and GH products had mean T(g) ranging from -46 degrees C to -30 degrees C. The in vivo specimens also exhibited a second, higher-temperature glass transition of unknown origin. Results suggest that the Ormco and GH products should have greater flexibility than the RMO products and that there should be significant differences in clinical force-degradation behavior for the Ormco and GH products compared with the RMO products.

Background: There are studies that either deal with the stigmatization patients anticipate or with patients’ concrete stigmatization experiences. Up until now, however, research is short of studies that investigate both aspects of subjective stigmatization simultaneously. Aims: This study aims at investigating to what extent patients with schizophrenia or depression anticipate and experience stigmatization and how this is influenced by the type of mental disorder and the social environment. Method: A total of 210 patients with schizophrenia or a depressive episode were interviewed, one half living in a city and the other in a small town. Results: Most of the patients expect negative reactions from the environment, particularly as concerns the access to work. Concrete stigmatization experiences were most frequently reported in the domain of interpersonal interaction. Even though schizophrenia patients and patients with depression anticipated stigmatization similarly frequently, the former reported concrete stigmatization experiences more frequently than the latter. Conversely, patients living in a small town anticipated stigmatization more frequently than patients from the city, even though both had actually experienced stigmatization at a similar rate. Conclusion: The results underline the necessity to differentiate between anticipated and experienced stigmatization. This is highly relevant for planning interventions aimed at reducing the stigma of mental disorder.

BACKGROUND Citizens of Novosibirsk were questioned regarding their ideas about schizophrenia and depressive disorders, with one of the main concerns being a comparison with the ideas and attitudes of the German population. METHOD In 2002, a representative survey (N = 745) was conducted among the adult population of Novosibirsk, using a fully structured interview that has been used in previous surveys in Germany. RESULTS Symptoms of schizophrenia were more frequently identified as an indication of mental disorder than were depressive symptoms. Psychosocial stress and biological influences were similarly frequently seen as the cause of schizophrenia, with the former prevailing among the respondents in the case of depressive symptoms. Psychotherapy was most frequently recommended as a treatment measure, also for schizophrenia. Supposing that no treatment measures will be taken, respondents assessed the prognosis for both mental disorders negatively. Conversely, interviewees gave a positive treatment prognosis. DISCUSSION Respondents from Germany and Novosibirsk showed similar beliefs, especially as regards the importance of biological influences and psychosocial stress and the assessment of psychotherapy as compared to psychopharmacology. However, German and Russian respondents also held differing views: a comparatively strong tendency of the Russian population to consider mental disorders as self-inflicted - an important finding that could shape future anti-stigma programs.

Aims: To assess the extent to which the German public supports the allocation of financial resources to the care of people with alcoholism and to research on alcoholism as compared with other conditions. Methods: 5025 interviews were conducted in the scope of a representative survey in Germany during May and June of 2001, using a personal, fully structured interview. Results: Respondents most frequently selected alcoholism as the disease for which medical care expenditures could be spared and cut down and on which research funds should neither be spent in the first place nor should be spent at all. Conclusion: Our study shows that despite the spread of the concept 'alcoholism is an illness', this disease is still treated 'unfavourably' compared to other conditions. Health campaigns that increase the public's awareness that alcoholism is not a personal failure but an illness with severe medical and social consequences may help reduce the public acceptance of structural discrimination.

QUESTION The goal of this study is to investigate the stigma of mental illness from the perspective of the persons directly affected by it. METHOD 210 patients with schizophrenia or major depression were questioned about anticipated and concrete stigmatization experiences, using a questionnaire especially developed for this study. RESULTS Most of the patients expected negative reactions from the environment. Three quarters were convinced that their job application would be rejected when it became known that they are mentally ill. Almost two thirds felt apprehensive that others would avoid them due to their illness. There is hardly any difference between schizophrenia and depressive patients' assessment of stigmatization of mentally ill people. Concrete stigmatization experiences were most frequently reported in the domain of interpersonal interaction. Second comes the distorted picture of mentally ill people that is depicted in the media and experienced as hurtful by the patients. The obstacles to access social roles (partnership, work, etc.) perceived by the patients come third. Participants least frequently mentioned structural discrimination, i. e. disadvantages regarding psychiatric treatment or rehabilitation measures. Contrary to anticipated stigmatization, there are differences between the two diagnostic groups when it comes to concrete stigmatization experiences. Schizophrenia patients more frequently report that others would avoid contact with them and that the access to social roles was especially complicated for them. They also seemed to be more exposed to structural discrimination than depressive patients. CONCLUSION Based on the results of this study, ways are discussed of how stigmatization and discrimination of mentally ill people can be reduced.

Background: In a population survey that was carried out in 1990, differences between the former Federal Republic of Germany and the German Democratic Republic were observed with regard to the social representation of depression. Back then, we predicted that in a few years these differences would have reduced. To test this hypothesis, a second survey was conducted in 2001.

The purpose of this study was to determine whether gender affects high-stakestest performance among dental students. Our sample consisted of 128 women and 323 men from six consecutive dental classes for which we recorded AADSAS overall and science predental GPAs; Dental Admission Test (DAT) scores; National Board Dental Examination (NBDE) I and II scores and pass/fail status; North East Regional Board of Dental Examiners (NERB) pass/fail status; and cumulative GPAs following the spring quarter of year two and summer quarter of year four of dental school. DAT scores, when controlled for previous academic performance, revealed that men significantly outperformed women in all areas except reading comprehension and biology, where the women's scores significantly exceeded the men's and were comparable, respectively. NBDE I results favored men and approached significance (p = 0.066), while for Part II men significantly outscored women. NBDE I and II and NERB pass rates showed no significant differences. These board results were also controlled for previous academic performance. Although we found that differences existed between genders, which appear to be the ramification of the classic high-stakes dilemma (women do as well as men in the classroom and on course-related tests, but less well on gatekeeper board exams), the context mitigates their operational effects. DAT differences are likely reduced by most admissions processes, but may be problematic when selected predictive algorithms are used. Practically, the NBDE I and II results are unlikely to meaningfully influence women's academic progress in dental school or postgraduate education admissions due to their magnitude and timing.

The difficulty of achieving an ideal or normal occlusion might lie in the pretreatment occlusion, patient-associated factors, and the treatment. The purpose of this study was to identify factors that were related to the treating orthodontist's posttreatment categorization of a case as difficult or easy. Ten orthodontists each identified 10 easy cases and 10 difficult cases that they had treated. The initial malocclusion was measured with the peer assessment rating (PAR) index and the index of orthodontic treatment need (IOTN). Patient and treatment information was obtained from the treatment records. Statistical analysis with parametric or nonparametric testing was performed. Difficult cases had greater severity and need before treatment and greater residual malocclusion and need after treatment. Difficult cases had more chart entries for problems with hygiene and compliance. They were more likely to have had extractions and changes in treatment plan. Difficult cases also required more appointments and a longer treatment duration. Three logistic regression models were developed based on malocclusion severity, patient characteristics, and treatment characteristics. The models support a correlation between greater pretreatment malocclusion severity, 1-phase treatment, and the designation as a difficult case. This study supports a model in which malocclusion severity and factors associated with the patient and the treatment contribute to an orthodontist's categorization of a case as easy or difficult.

Alzheimer's disease (AD) is characterized, amongst others, by the appearance of vascular and parenchymal β-amyloid deposits in brain. Such aggregates are mainly composed of β-amyloid peptides, which are derived by proteolytic processing of a larger amyloid precursor protein (APP). APP is highly conserved among mammalian species, but experimental studies in rodents are often hampered by the humble APP-processing in the amyloidogenic pathway and by the inability of rodent β-amyloid peptides to form higher molecular aggregates such as soluble oligomers and insoluble β-amyloid plaques. Thus, there is need for in vitro and in vivo model systems that allow identification of factors that increase amyloidogenic APP processing and accelerate β-amyloid plaque formation and testing the potency of pharmacological manipulations to ameliorate β-amyloid load in brain. Transgenic mice that overexpress human APP containing AD-associated mutations that favor the amyloidogenic pathway of APP processing represent such a model. However, mutations of the APP gene are not frequent in AD and, therefore, the mechanisms of β-amyloid plaque formation, the composition of β-amyloid plaques, and the accompanying tissue response in brain of these animals may be different from that in AD. In contrast, guinea pigs express β-amyloid peptides of the human sequence and appear to represent a more physiological model to examine the long-term effects of experimental manipulations on APP processing and β-amyloid plaque formation in vivo. Additionally, APP processing in guinea pig primary neuronal cultures has been shown to be similar to cultures of human origin. In this article we highlight the advantages and limitations of using guinea pigs as experimental models to study APP processing.

Fabry disease is an inherited lysosomal storage disorder caused by deficiency of the enzyme α-galactosidase A. The enzyme deficiency results in accumulation of glycosphingolipids in the lysosomes n nearly all cell types and tissues leading to a multisystem disease. Manifestations include painful crisis, angiokeratomas, corneal dystrophy, and hypohydrosis. The severe renal, cerebrovascular, and cardiac involvement is predominantly responsible for premature mortality in Fabry patients. The disease is X-linked and manifests primaryly in hemizygous males but also heterozygous females can be affected. Cardiac Involvement is frequent in Fabry disease. Patients develop hypertrophic cardiomyopathy, arrhythmias, conduction abnormalities, and valvular abnormalities. Although Fabry disease leads to a complex clinical syndrome, there are studies indicating that manifestations can be limited to the heart. The isolated cardiac variant of Fabry disease seems to be more common than previously thought: around 3–6% of male patients with left ventricular hypertrophy seem to suffer from this disease variant. Enzyme Replacement Therapy: Recent advances in molecular biology and genetic engineering have enabled the devleopment of enzyme replacement therapy in Fabry disease. Results from two independent therapy studies are indeed promising: Infusion of the enzyme preparation seems to be well tolerated and effective in catabolizing the lipid deposits. This enzyme replacement therapy could be one of the first examples for causal treatment of left ventricular hypertrophy. Therefore, early diagnosis of hypertrophy patients with the cardiac variant of Fabry disease is important.

Orthodontic studies over several decades have found generally inconsistent opinions among dentists when evaluating orthodontic treatment need. There has also been recent concern that dental school education does not sufficiently prepare dentists to diagnose malocclusion and make appropriate referrals of potential orthodontic patients. The purpose of this study was to investigate the efficacy of using the index of orthodontic treatment need (IOTN) as a tool to improve dental students' ability to assess orthodontic treatment need. Fourth-year dental students were randomly divided into control, sham-control, and experimental groups stratified for mean grade point average. On 2 occasions, the subjects evaluated 30 orthodontic study models with a gold standard previously established by an expert panel of 15 orthodontists for orthodontic treatment need. The experimental group reevaluated the models after IOTN instruction. Kappa statistics, sensitivity, and specificity were calculated for each subject. Analysis of covariance (ANCOVA) showed that the experimental group had significantly higher agreement with the expert panel after IOTN training than did either control group. IOTN is a promising teaching aid for improving educational outcomes for orthodontic referral.

Anderson Fabry disease is a life threatening, X-linked inborn metabolic defect of the lysosomal enzyme áalpha-galactosidase A. The deficiency of alpha-galactosidase A leads to a progressive accumulation of globotriaosylceramide (Gb(3)), the major glycosphingolipid substrate of the enzyme, within vulnerable cells, tissues, and organs, including the cardiovascular system. Cardiac involvement is frequent and patients with cardiac affection develop progressive hypertrophic infiltrative cardiomyopathy, valvular abnormalities, arrhythmias, and conduction abnormalities and may develop coronary heart disease. Hemizygous male patients have no detectable alpha-galactosidase A activity, while affected heterozygous females may have normal level of alpha-galactosidase A activity. Death occurs in male patients at 45 to 50 years, about 15 to 20 years earlier than in female patients due to a vicious circle from chronic renal insufficiency, arterial hypertension, atherosclerotic lesions and cerebrovascular hemorrhage or insults, and cardiomyopathy. Cardiac involvement in hetero- and hemizygotes will be discussed as well as the influence of enzyme replacement of alpha-galactosidase A.

Celiac disease (CD) is a condition related to the small intestine's intolerance to gluten. The diagnosis of CD can be difficult, especially because patients may exhibit a wide spectrum of signs and symptoms. It is important to identify this disease process early because affected individuals have an increased risk for developing lymphoma of the gut. Our objective was to evaluate whether patients with CD have a significantly higher prevalence of recurrent aphthous stomatitis compared with the general population, as some investigators have speculated. Therefore, we screened 61 patients with diagnosed CD for the presence of, or a positive history of, aphthous ulcerations. We then statistically compared this data with a randomly selected control population, matched for age and gender, but without CD. Our results demonstrated no significant differences between groups for age, gender, or prevalence of recurrent aphthous stomatitis.

Cellular homeostatic adaptation to cerebral ischemia is complex and contains changes in receptor mediated gene expression and signaling pathways. The proteins of the immediate early genes c-Fos and c-Jun are thought to be involved in coupling neuronal excitation to target gene expression, due to formation of heterodimers and binding to the AP1 promotor region. We used an in vitro model to compare ischemia induced c-Fos and c-Jun expression in rat neuronal cell cultures and nerve growth factor (NGF) differentiated PC 12 cells. Since activation of glutamate receptors is known to mediate ischemic injury we determined the effect of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK 801 on c-Fos and c-Jun expression in both cell culture systems during ischemia. Neuron rich cultures and NGF differentiated PC 12 cells were exposed to sublethal in vitro ischemia using an hypoxic chamber flushed with argon/CO2 (95 %/5%). C-Fos and c-Jun mRNA expression was analyzed by competitive reverse transcription-polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as internal standard. One hour of in vitro ischemia significantly increased c-Fos and c-Jun mRNA levels in both cell culture systems. In neuron rich cultures a 10-fold (c-Fos) and 7-fold (c-Jun) mRNA increase was observed. The mRNA rise was less pronounced in PC 12 cells (5.5-fold and 2-fold) for c-Fos and c-Jun, respectively. The addition of MK 801 significantly reduced the expression of c-Fos and c-Jun mRNA in neuronal cultures, whereas no effect was detectable in PC 12 cells. Since MK 801 failed to reduce the c-Fos and c-Jun expression in NGF differentiated PC 12 cells different signaling pathways may initiate c-Fos and c-Jun expression in both cell culture systems.

Purpose: Remifentanil is a new, short-acting opioid that is similar pharmacodynamically to currently available opioids but differs in its pharmacokinetics. In the present study, we compared the use of remifentanil with the use of meperidine during intravenous conscious sedation for third molar surgery. Patients and Methods: Forty patients who were scheduled for the removal of impacted third molars were randomly assigned to undergo 1 of 2 intravenous conscious sedation techniques. For both groups, 50:50 nitrous oxide oxygen were administered via nasal hood, and midazolam was titrated to Verril's sign. Twenty patients each then received either remifentanil 0.05 μg/kg/min or meperidine 50 mg. Both patients and surgeons were blinded to the narcotic that was used. Blood pressure, heart rate, and oxygen saturation were determined before sedation and every 5 minutes during surgery. Recovery was measured using serial Trieger tests every 5 minutes after surgery. Patient and surgeon satisfaction of the quality of sedation was measured with a visual analog scale. Results: Peak heart rate (91 beats/min for remifentanil vs 107 beats/min for meperidine, P < .01) and peak systolic blood pressure (131 mm Hg for remifentanil vs 142 mm Hg for meperidine, P < .05) were significantly lower for the remifentanil group. Although there was a trend toward increased surgeon satisfaction with remifentanil (86 of 100 with remifentanil vs 73 of 100 with meperidine), it was not found to be statistically significant. Likewise, other physiologic parameters were not found to be statistically significant. Conclusions: The lower peak heart rate and systolic blood pressure levels indicate that remifentanil may allow for less fluctuation in cardiovascular parameters. This could prove beneficial in patients with cardiovascular compromise. © 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:244-250, 2002

Background: In contrast to the immunosupressed patient population, the prevalence of fluconazole-resistant strains of Candida albicans among healthy individuals has not been extensively studied. Methods: Candida species were cultured form 50 healthy outpatients with clinical signs of oral candidiasis. Following one week of the recommended fluconazole regimen, post-treatment cultures were obtained. Both pre- and post-treatment yeasts were identified and in vitro susceptibility testing was performed using the NCCLS M-27A method. Strains were further differentiated using established cDNA probes. Results: Forty-four patients (88%) had positive C.albicans cultures prior to treatment. Antifungal susceptibility testing of these strains demonstrated no in vitro resistance to fluconazole. At post-treatment evaluation, eight patients (18%) had persistent signs of infection and 10 patients (23%) had positive Candida sp. cultures despite no clinical signs of infection. DNA analysis confirmed that the same C. albicans strain was present both in the pre-treatment and the post-treatment cultures. Conclusions: Our results showed that the presence of fluconazole-resistant strains of C.albicans does not appear to be prevalent among healthy outpatients furthermore, in vitro antifungal susceptibility testing does not always predict successful therapy in these patients.

Audio- or videotaping and one-way mirrors are often used in clinical supervision. Yet, the effects of audio- or videotaping on supervisees have yielded equivocal results. Some studies suggest that audio- or videotaping increases trainee anxiety and hinders performance, whereas other studies suggest negligible effects. The authors present 2 studies in which they tested self-focused attention theory (e.g., C. S. Carver & M. F. Scheier, 1982; S. Duval & R. A. Wicklund, 1972) to explain the equivocal findings. In each study, trainees were randomly assigned to 1 of 3 awareness conditions (private or public self-awareness, or subjective awareness) and conducted initial counseling sessions. Analyses of supervisee anxiety and performance found no significant differences due to self-awareness condition in either study. The results suggest that a mirror and audio- or videotaping elicit trivial aversive effects on supervisees.

The human immune system is regulated by a broad network of co-inhibitory and co-stimulatory receptors that control the type, scale, and duration of immune responses. These receptors are now recognized as promising immunotherapy targets for the treatment of many cancers and autoimmune diseases. Immunotherapies that block co-inhibitory receptors such as PD-1 and CTLA-4 are showing unprecedented efficacy in the treatment of some tumors, and have generated interest in the characterization of additional immunotherapy targets that may broaden the number of patients who can be helped by these drugs. Immunotherapy research programs are now exploring a wide range of both co-inhibitory (e.g. LAG-3, TIGIT, Tim-3) and co-stimulatory (e.g. GITR, 4-1BB, OX40) receptors, individually and in combination. Quantitative and reproducible functional bioassays are essential tools in the development of biologics for cancer immunotherapy. Most existing assays rely on primary cells and suffer from lengthy protocols and high day-to-day and donor-to-donor variability. These approaches are cumbersome, error-prone, and do not produce data of the quality required for drug development in a quality control environment. To address this, we have developed a suite of cell line-based reporter bioassays for co-stimulatory immune checkpoint targets including GITR, 4-1BB, OX40, and CD40. In these assays, stable cell lines express luciferase reporters driven by response elements under the precise control of intracellular signals mediated by each co-stimulatory receptor. These bioassays reflect mechanisms of action for drug candidates designed for each co-stimulatory receptor and demonstrate high specificity, sensitivity and reproducibility. Reporter-based bioassays can serve as powerful tools in immunotherapy drug development for antibody screening, potency testing and stability studies. Citation Format: Julia K. Gilden, Jun Wang, Michael Beck, Jamison Grailer, Jim Hartnett, Frank Fan, Mei Cong, Zhe-jie Jey Cheng. Quantitative cell-based assays for characterization of antibodies targeting co-stimulatory immune checkpoint receptors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5672. doi:10.1158/1538-7445.AM2017-5672

Name of the disease (synonyms) Fabry disease, Anderson-Fabry disease. OMIM# of the disease 301500. Name of the analysed gene(s) or DNA/chromosome segments Alpha-galactosidase A, GLA. OMIM# of the gene(s) 300644. Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the GLA gene in diagnostic, predictive and prenatal settings for Fabry disease and for risk assessment in patients’ relatives.

Objective Tonsillar hypertrophy caused by the progressive accumulation of partially degraded glycosaminoglycans (GAGs) within the cells is a typical symptom in patients with mucopolysaccharidoses (MPS). We studied the tissue of adenoids and tonsils of patients suffering from MPS with special regard to characteristic morphological features serving as possible markers for diagnosis. Methods Adenoids of 87 patients and tonsils of 4 patients with MPS (2 patients with MPS I, 7 MPS II, 5 MPS IV and 10 MPS VI and 63 controls) and controls were examined. Examinations were repeated in a blinded manner by two pathologists. Results The key feature observed was a subepithelial “clearing” on scanning magnification, induced by perivascular accumulation of histiocytoid cell forms. Similar agglomerates could sometimes be found at the base of lymphoid follicles. In the blinded assessment a specificity of 92% (100% for adenoids) and a sensitivity of 100% were achieved. The inter-observer-consistency was 92% (100% for adenoids). In tonsillectomy specimens marked subepithelilal fibrosis can lead to a false-negative evaluation. Conclusions Qualified histological examination could be an option for early diagnosis of MPS.

Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births and are a common cause of pediatric neurodegenerative disease. The relatively small number of patients with LSDs and lack of validated biomarkers are substantial challenges for clinical trial design. Here, we evaluated the use of a commercially available fluorescent probe, Lysotracker, that can be used to measure the relative acidic compartment volume of circulating B cells as a potentially universal biomarker for LSDs. We validated this metric in a mouse model of the LSD Niemann-Pick type C1 disease (NPC1) and in a prospective 5-year international study of NPC patients. Pediatric NPC subjects had elevated acidic compartment volume that correlated with age-adjusted clinical severity and was reduced in response to therapy with miglustat, a European Medicines Agency–approved drug that has been shown to reduce NPC1-associated neuropathology. Measurement of relative acidic compartment volume was also useful for monitoring therapeutic responses of an NPC2 patient after bone marrow transplantation. Furthermore, this metric identified a potential adverse event in NPC1 patients receiving i.v. cyclodextrin therapy. Our data indicate that relative acidic compartment volume may be a useful biomarker to aid diagnosis, clinical monitoring, and evaluation of therapeutic responses in patients with lysosomal disorders.

Introduction Previous research has demonstrated that current methods of informed consent are relatively ineffective as shown by poor recall and comprehension by adolescent patients and their parents. The purpose of this study was to determine whether adding a short videotape presentation reiterating the issues related to informed consent to a modified informed consent document that emphasizes a limited number of core and patient-specific custom "chunks" at the beginning of an informed consent presentation improved the recall and comprehension of the risks, benefits, and alternatives of orthodontic treatment. A second objective was to evaluate the current related data for recommendable practices. Methods Seventy patient-parent pairs were randomly divided into 2 groups. The intervention group (group A) patients and parents together reviewed a customized slide show and a short videotape presentation describing the key risks of orthodontic treatment. Group B followed the same protocol without viewing the videotape. All patients and parents were interviewed independently by research assistants using an established measurement tool with open-ended questions. Interviews were transcribed and scored for the appropriateness of responses using a previously established codebook. Lastly, the patients and parents were given 2 reading literacy tests, 1 related to health and 1 with general content followed by the self-administered demographic and psychological state questionnaires. Results There were no significant differences between the groups for sociodemographic variables. There were no significant differences between the groups for overall recall and comprehension; recall and comprehension for the domains of treatment, risk, and responsibility; and recall and comprehension for core, general, and custom items. The positional effects were limited in impact. When compared with previous studies, these data further demonstrate the benefit of improved readability and audiovisual supplementation with the addition of "chunking." Conclusions There is no benefit to adding a short video to the previously established improved readability and audiovisual supplementation. There is a significant benefit of improved readability and audiovisual slide supplementation with the addition of "chunking" over traditional informed consent methods in terms of patient improvement in overall comprehension, treatment recall, and treatment comprehension. The treatment domain is the most affected.

Niemann-Pick type C (NPC) is a neurodegenerative lysosomal storage disorder caused by defects in the lysosomal proteins NPC1 or NPC2. NPC cells are characterized by reduced lysosomal calcium levels and impaired sphingosine transport from lysosomes. Natural killer (NK) cells kill virally infected/transformed cells via degranulation of lysosome-related organelles. Their trafficking from lymphoid tissues into the circulation is dependent on sphingosine-1-phosphate (S1P) gradients, sensed by S1P receptor 5 (S1P5). We hypothesized that NK-cell function and trafficking could be affected in NPC disease due to the combined effects of the lysosomal calcium defect and sphingosine storage. In an NPC1 mouse model, we found the frequency of NK cells was altered and phenocopied S1P5-deficient mice, consistent with defects in S1P levels. NK cells from NPC1 mice also had a defect in cytotoxicity due to a failure in degranulation of cytotoxic granules, which was associated with reduced lysosomal calcium levels. Affected NPC1 patients and NPC1 heterozygote carriers had reduced NK-cell numbers in their blood and showed similar phenotypic and developmental changes to those observed in the NPC1 mouse. These findings highlight the effects of lysosomal storage on the peripheral immune system.

Several occlusal indexes are currently used to ascertain eligibility for orthodontic treatment. A comparison of 3 indexes of orthodontic treatment need was made with the consensus opinion of a panel of 15 experienced orthodontists. Sets of study casts (170) representing the full spectrum of malocclusions were selected. An examiner, calibrated in the Dental Aesthetic Index, the Handicapping Labiolingual Deviation with the California Modification, and the Index of Orthodontic Treatment Need, scored the casts. The panel of orthodontists individually rated the same casts for their degree of orthodontic treatment need. The mean rating of the panel on the need for treatment was used as the gold standard for evaluating the validity of the indexes. Intrarater and interrater reliability was high (kappa > 0.8). Overall accuracy of the indexes, as reflected in area under receiver-operating characteristic curves, was also high: Dental Aesthetic Index, 95%; Handicapping Labiolingual Deviation with the California Modification, 94%; and Index of Orthodontic Treatment Need, 98%. Cutoff points for the indexes that resulted in the closest agreement with the gold standard differed from the published cutoff points for the indexes. The indexes appear to be valid measures of treatment need as perceived by orthodontists. The published cutoff points for the indexes were more conservative in assigning patients for treatment than a panel of orthodontists. However, adjusting the cutoff points moved all 3 indexes into close agreement with the experts.

An inherited deficiency in beta-galactosidase can result in GM1 gangliosidosis, with several phenotypes of generalized or chronic psychomotor deterioration, as well as in Morquio disease type B, a characteristic mucopolysaccharidosis free of neurological symptoms. We performed mutation analyses in 17 juvenile and adult patients from various European regions with a deficiency in beta-galactosidase and skeletal abnormalities. Fifteen of these had the Morquio B phenotype and have remained neurologically healthy until now while the two others exhibited psychomotor retardation of juvenile onset. A two-base substitution (851-852TG--CT; W273L) was present in 14 of the 15 Morquio B cases. Even if one excludes alleles from patients with possible common descent, there was a much higher frequency (79%) among those with Morquio B phenotype for the W273L mutation than previously reported in the literature (37%). That the Morquio phenotype is also expressed in heterozygotes for W273L and alleles typically found in GM1 gangliosidosis makes it possible to predict the phenotype and reliably detect heterozygotes. A single French patient had a novel missense point mutation (Q408P) together with a known mutation (T500A) while the mentally retarded patients were both heterozygous for two mutations known in chronic GM1 gangliosidosis together with two novel missense point mutations (Y270D and H281Y) in the vicinity of W273L. Our results confirm the high impact of Trp 273 for the function of beta-galactosidase and the expression of the Morquio B phenotype. In addition, a second domain around the amino acids 400-500 may also be of significance.

Der faktorielle Survey ist eine Methode, mit der Situationen, die komplexe Konstellationen von Merkmalen darstellen, von Befragten im Rahmen eines Interviews bewertet werden. So konnte ermittelt werden, inwieweit die Dimensionen „Rauchverbot“ und „Anzahl der Personen, die rauchen“ fur die Geltung einer Nichtraucher-Norm von Bedeutung sind. Hierzu werden die Merkmale (d.h. Auspragungen) der Dimensionen zu Situationsbeschreibungen kombiniert. Jede der moglichen und sinnvollen Situationsbeschreibungen wird dann von Befragten beurteilt. So konnte eine Situation, in der „Rauchen verboten“ angezeigt wird und in der trotzdem mehr als die Halfte der anwesenden Personen raucht, danach beurteilt werden, inwieweit eine Person in dieser Situation rauchen darf. Der Aufsatz hat zum einen das Ziel, die Methode des faktoriellen Surveys vorzustellen, die in Deutschland bisher kaum angewendet wurde und die fur die Losung einer Reihe zentraler sozialwissenschaftlicher Fragen angewender werden konnte. Das zweite Ziel dieses Aufsatzes ist zu zeigen, inwieweit der faktorielle Survey fur die Messung von Normen geeignet ist. Wir behandeln im Einzelnen die Schritte bei der Durchfuhrung eines faktoriellen Surveys und diskutieren dabei die jeweiligen Probleme. Schlieslich werden zwei neue Computerprogramme vorgestellt, die die Durchfuhrung faktorieller Surveys erheblich erleichtern.

The purpose of this retrospective longitudinal study was to compare 7 cephalometric measurements of the cranial base in subjects with Class I and Class II skeletal patterns at ages 1 month, 2 years, and 14 years. A sample of 22 Class I and 21 Class II subjects was selected; the inclusion criteria were overjet, ANB, and Harvold unit difference. Analyses of head circumference, crown-rump length, and weight revealed no significant (P.15) differences between the Class I and Class II infant subjects at the initial age (1 month). One angular and 6 linear measurements were first compared with a multivariate analysis of variance, which revealed significant effects for age (P.0001) and the age by skeletal pattern interaction (P =.0266) but not for skeletal pattern (P =.3705). Analyses of variance showed significant (P.0001) age effects for each of the cephalometric variables but no significant skeletal pattern effects (P.10). The anterior cranial base measurement of nasion to sphenoethmoidal suture was the only variable found to have a significant age by skeletal pattern interaction (P.006), which revealed a difference in the timing of its growth spurt that occurred between 1 month and 2 years in the Class I subjects and between 2 years and 14 years in the Class II subjects. There were no significant differences between the skeletal classes at any of the 3 ages evaluated. Conclusions from this study indicate that cranial base growth patterns are similar for Class I and Class II subjects and that the premise of a more obtuse "saddle angle" or cranial base angle in Class II skeletal patterns was not supported.

We describe the development of a table top soft X-ray source based on a laser produced plasma. The plasma is produced by a Nd:YLF pulse-train laser which delivers pulse trains of up to 400 pulses each of about 25 ps duration. Number and energy of the micropulses are fully computer controlled adjustable for an optimum interaction with a rotating solid target. Spectral, spatial and temporal characteristics of the X-ray emission from Mylar and copper targets have been studied. A calibrated back-illuminated CCD camera together with a slit grating spectrograph were utilized for the measurement of the absolute soft X-ray photon fluxes. The temporal measurements were performed using a streak camera while the plasma size was measured with a zone plate. An application of the system in a X-ray absorption experiment is shown. The advantages of the system in view of possible optical pump and soft X-ray probe experiments will be discussed.