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Milder Forms (milder + form)
Selected AbstractsProphylactic therapy for haemophilia: early experienceHAEMOPHILIA, Issue 2003E. Berntorp Summary., During the 1960s, it was reported from Sweden that haemophiliacs with factor levels above 1% rarely develop arthropathy. This observation suggested that severe haemophilia could be converted to a milder form by regular infusions with factor concentrate. After several earlier publications, a report was published in 1992 that detailed 25 years' experience with prophylaxis in 60 patients from the Malmö centre. The results showed that starting prophylaxis early in life with a dose regimen that would prevent factor VIII or IX plasma levels from falling below 1% could prevent the development of haemophilic arthropathy. Also, older age groups who had received less intensive treatment, and who started prophylaxis later in life, were still in a much better condition than historic controls. In the 1970s several small but well-controlled studies from the USA, Germany and Italy clearly showed the benefit of prophylaxis in reducing bleeding frequency. Early experience from the Netherlands was published in 1971. Since these early studies, the results have been corroborated from many countries and in a large multinational study. Although the benefits of prophylaxis seem unquestionable, several research questions remain to be better elucidated, such as when to start and when to stop, dosing and dose interval, and how to assess the long-term treatment effects. These issues are of great economic importance, and the need for health economical studies is obvious. [source] High cortical spreading depression susceptibility and migraine-associated symptoms in Cav2.1 S218L miceANNALS OF NEUROLOGY, Issue 1 2010Arn M. J. M. van den Maagdenberg PhD Objective The CACNA1A gene encodes the pore-forming subunit of neuronal CaV2.1 Ca2+ channels. In patients, the S218L CACNA1A mutation causes a dramatic hemiplegic migraine syndrome that is associated with ataxia, seizures, and severe, sometimes fatal, brain edema often triggered by only a mild head trauma. Methods We introduced the S218L mutation into the mouse Cacna1a gene and studied the mechanisms for the S218L syndrome by analyzing the phenotypic, molecular, and electrophysiological consequences. Results Cacna1aS218L mice faithfully mimic the associated clinical features of the human S218L syndrome. S218L neurons exhibit a gene dosage,dependent negative shift in voltage dependence of CaV2.1 channel activation, resulting in enhanced neurotransmitter release at the neuromuscular junction. Cacna1aS218L mice also display an exquisite sensitivity to cortical spreading depression (CSD), with a vastly reduced triggering threshold, an increased propagation velocity, and frequently multiple CSD events after a single stimulus. In contrast, mice bearing the R192Q CACNA1A mutation, which in humans causes a milder form of hemiplegic migraine, typically exhibit only a single CSD event after one triggering stimulus. Interpretation The particularly low CSD threshold and the strong tendency to respond with multiple CSD events make the S218L cortex highly vulnerable to weak stimuli and may provide a mechanistic basis for the dramatic phenotype seen in S218L mice and patients. Thus, the S218L mouse model may prove a valuable tool to further elucidate mechanisms underlying migraine, seizures, ataxia, and trauma-triggered cerebral edema. ANN NEUROL 2010;67:85,98 [source] Pregnancy outcome in women with heart disease undergoing induction of labourBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 7 2004Galia Oron Objective To examine the safety and outcome of induction of labour in women with heart disease. Design Prospective single-centre comparative study. Setting Major university-based medical centre. Population/Sample One hundred and twenty-one pregnant women with heart disease. Methods The sample included all women with acquired or congenital heart disease who attended our High-Risk Pregnancy Outpatient Clinic from 1995 to 2001. The files were reviewed for baseline data, cardiac and obstetric history, course of pregnancy and induction of labour and outcome of pregnancy. Findings were compared between women who underwent induction of labour and those who did not. Forty-seven healthy women in whom labour was induced for obstetric reasons served as controls. Main outcome measures Pregnancy outcome. Results Of the 121 women with heart disease, 47 (39%) underwent induction of labour. There was no difference in the caesarean delivery rate after induction of labour between the women with heart disease (21%) and the healthy controls (19%). Although the women with heart disease had a higher rate of maternal and neonatal complications than controls (17%vs 2%, P= 0.015), within the study group, there was no difference in complication rate between the patients who did and did not undergo induction of labour. Conclusion Induction of labour is a relatively safe procedure in women with cardiac disease. It is not associated with a higher rate of caesarean delivery than in healthy women undergoing induction of labour for obstetric indications, or with more maternal and neonatal complications than in women with a milder form of cardiac disease and spontaneous labour. [source] Mutations in GCK and HNF-1, explain the majority of cases with clinical diagnosis of MODY in SpainCLINICAL ENDOCRINOLOGY, Issue 4 2007Itziar Estalella Summary Objective, The aim of this study was to group patients with MODY (maturity-onset diabetes of the young) according to the genetic alterations underlying the disease and to investigate their clinical characteristics. Patients and methods, Molecular analysis of GCK (MODY2), HNF-1, (MODY3), HNF-4, (MODY1) and HNF-1, (MODY5) genes was performed by DNA sequencing in 95 unrelated index probands (47M/48F; mean age 9·9 ± 5·2 years) with clinical diagnosis of MODY. After classification into MODY subtypes according to the genetic alterations, clinical characteristics were compared between the groups. Results, Seventy-six families were shown to carry mutations in GCK (34 of them previously unreported), eight families presented HNF-1, mutations, and a large genomic rearrangement in HNF-1, was found in a family. No alteration was found in HNF-4,. Thus, relative frequencies in the group studied were 80% MODY2, 8·5% MODY3 and 1% MODY5. Comparison of clinical parameters according to genetic status showed significant differences between MODY2 and MODY3 patients in age at diagnosis (9·4 ± 5·4 years vs. 12·7 ± 4·6 years), diagnosis (impaired glucose tolerance vs. diabetes), diagnostic test used (OGTT vs. fasting glucose), treatment (diet and exercise vs. insulin/oral antidiabetic agents) and birth weight (2·96 ± 0·44 kg vs. 3·40 ± 0·67 kg). Conclusion, Almost 90% of the MODY cases in the group studied are explained by mutations in the major genes GCK (MODY2) and HNF-1,(MODY3), although differences in the relative prevalence of each form could be partly due to patient referral bias (paediatric vs. adult). In general, patients with MODY2 were diagnosed at an earlier age in life than MODY3 patients and had a milder form of diabetes. Moreover, the majority of patients with MODY2 mutations were treated with diet whereas half of MODY3 patients received pharmacological treatment. [source] Knowledge of disease and adherence in adult patients with haemophiliaHAEMOPHILIA, Issue 4 2010K. LINDVALL Summary., Patients with moderate and severe haemophilia are evaluated on a regular basis at their haemophilia centres but patients with mild haemophilia are seen less often because of fewer problems related to their disease. The needs of patients with milder forms of haemophilia, however, are often underestimated, both by the patient and staff at healthcare facilities. This study evaluated the knowledge of disease and adherence to treatment among patients with severe, moderate and mild haemophilia. This was a prospective multicentre study performed in Haemophilia Centres in Scandinavia. A total of 413 (67%) of 612 patients aged >25 years with mild, moderate and severe haemophilia completed a self-administered questionnaire. The mean age of the respondents was 49.7 years (range 25,87 years). Of the 413 respondents, 150 had a mild, 86 had a moderate and 177 had a severe form of haemophilia. A total of 22 (5%) patients did not know the severity of their disease, and 230 (56%) patients knew the effect of factor concentrate in the blood. Of the 413 respondents, 53 (13%) of the cohort never treated a haemorrhage. Patients with mild haemophilia, P , 0.001, were the least likely to treat a haemorrhage. The relative number of patients who were afraid of virus transmission by factor concentrate was about similar in the three groups, 27% of those with severe haemophilia, 26% with moderate and 24% with mild haemophilia. This study shows that the amount of knowledge among haemophilia patients about their disease and treatment is somewhat limited, and demonstrates the importance of continually providing information about haemophilia and treatment, especially to patients with a mild form of the disease. [source] Social skills in children with intellectual disabilities with and without autismJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 5 2005A. De Bildt Abstract Background Social skills were studied in 363 children with mild intellectual disabilities (ID) and 147 with moderate ID with and without autism (age 4 through 18). The objective was to investigate the value of the Children's Social Behaviour Questionnaire (CSBQ), as a measure of subtle social skills, added to a measure of basic social skills with the Vineland Adaptive Behaviour Scales (VABS), in identifying children with ID with or without autism. Method Children with mild and moderate ID, with and without autistic symptomatology were compared on basic social skills, measured with the Communication and Socialization domains of the VABS, and subtle social skills, measured with the CSBQ. Results Measuring basic social skills is not sufficient in differentiating between levels of ID. Communicative skills and subtle social skills, that concern overlooking activities or situations and fear of changes in the existing situation, seem to play a far greater role. Additionally, with respect to identifying autistic symptomatology, basic social skills do not contribute, as opposed to communicative skills and the tendency to withdraw from others. Conclusions The results implicate that the CSBQ not only has specific value as a measure of subtle social skills to identify pervasive developmental disorders, but that the instrument also has a specific contribution to differentiating between the two levels of ID. Furthermore, our outcomes imply a slight difference between limitations in subtle social skills as mentioned by the AAMR (American Association on Mental Retardation 2002) and limitations in subtle social skills as seen in milder forms of pervasive developmental disorders. Clinical and theoretical implications will be discussed. [source] The Prevalence of Dental Caries and Fluorosis in Japanese Communities with Up to 1.4 ppm of Naturally Occurring FluorideJOURNAL OF PUBLIC HEALTH DENTISTRY, Issue 3 2000Akihito Tsutsui DDS Abstract Objective: The purpose of this study was to determine the relationship between the concentration of fluoride in drinking water and the prevalence of dental caries and fluorosis in seven Japanese communities with different concentrations of fluoride occurring naturally in the drinking water. Methods: A total of 1,060 10- to 12-year-old lifetime residents were examined to determine the prevalence of dental caries and fluorosis in communities with trace amounts to 1.4 ppm fluoride in the drinking water in 1987. Systemic fluorides (drops or tablets) have never been available in Japan and the market share of fluoride-containing toothpaste was 12 percent at the time of the study. Results: The prevalence of dental caries was inversely related and the prevalence of fluorosis was directly related to the concentration of fluoride in the drinking water. The mean DMFS in the communities with 0.8 to 1.4 ppm fluoride was 53.9 percent to 62.4 percent lower than that in communities with negligible amounts of fluoride. Multivariate analysis showed that water fluoride level was the strongest factor influencing DMFS scores. The prevalence of fluorosis ranged from 1.7 percent to 15.4 percent, and the increase in fluorosis with increasing fluoride exposure was limited entirely to the milder forms. Conclusions: The findings of this study conducted in 1987 in Japan parallel those reported by Dean et al. in the early 1940s. [source] Analysis of haemochromatosis gene mutations in a population from the Mediterranean BasinLIVER INTERNATIONAL, Issue 4 2001Salvatore Campo Abstract:Background/Aims: The C282Y mutation in the haemochromatosis gene (HFE) located on chromosome 6 has been identified as the main genetic basis of hereditary haemochromatosis (HH). Two more mutations of that gene, H63D and S65C, appear to be associated with milder forms of HH. A high allele frequency for C282Y and H63D mutations was reported in populations from North Europe, while incomplete information is available for individuals from the Mediterranean Basin where C282Y homozygotes comprise a smaller percentage of HH cases. In this study we investigated the allele frequency of HFE mutations and the association between HFE mutations and cases of HH in a population from the South of Italy (Sicily and Calabria). In addition, we evaluated a possible association between HFE mutations and either chronic liver disease or type II diabetes. Patients and Methods: Three hundred and twenty-seven individuals (654 chromosomes) were tested for C282Y, H63D and S65C mutations of the HFE gene by restriction fragment length polymorphism. Four had HH, 23 had hepatocellular carcinoma, 100 had chronic liver disease, 100 had type II diabetes, and 100 were healthy controls. Results: Both C282Y and S65C mutations were each detected in one of the 654 chromosomes analysed (allele frequency=0.15%), while H63D change was found in 122 chromosomes (allele frequency=18.6%) and was equally distributed in all the categories examined. One healthy individual had compound heterozygosity for C282Y and H63D mutations. The frequency of C282Y in this Southern Italian sample was the lowest yet reported for a population of European origin. None of the four HH patients was either homozygous or heterozygous for C282Y. Conclusions: In Mediterranean populations from Southern Italy the C282Y mutation occurs sporadically and HFE polymorphisms seem to have little diagnostic relevance. [source] Management of children with holoprosencephaly,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Eric B. Levey Abstract Holoprosencephaly (HPE) is the most common malformation of the embryonic forebrain in humans. Although HPE occurs along a continuous spectrum, it has been categorized into four types from most severe to least severe: alobar, semilobar, lobar, and middle interhemispheric (MIH) variant. Facial malformations are often associated with HPE and usually correlate with the severity of brain malformation. With the most severely affected newborns, there is a high mortality rate in the first month of life, however, with milder forms of HPE, the majority survive beyond infancy. The Carter Centers for Brain Research in Holoprosencephaly and Related Malformations have enrolled 182 living children in a prospective research study. Based on previously published reports using this database, reports from other investigators, as well as our experience and personal observations, the range of developmental, neurological, and medical problems found in children with HPE is described in this article. Virtually all children with HPE have some developmental disability and the severity correlates with the severity of the brain malformation on neuroimaging. Common medical problems include hydrocephalus, seizures, motor impairment, oromotor dysfunction with risk of poor nutrition and aspiration, chronic lung disease, gastroesophageal reflux, constipation, hypothalamic dysfunction with disturbed sleep,wake cycles and temperature dysregulation, as well as endocrine dysfunction. Diabetes insipidus in particular is found in about 70% of children with classic HPE. Recommendations for management of these problems are given based on experiences of the authors and familiarity with the literature. © 2010 Wiley-Liss, Inc. [source] Workplace Sexual Harassment Perceptions in the Turkish Context and the Role of Individual DifferencesAPPLIED PSYCHOLOGY, Issue 4 2010Yonca Toker The major purpose of this study was to examine perceptions of workplace sexual harassment in the Turkish context. In Study 1, 53 working women were interviewed to identify culture-relevant behaviors that are considered to be sexual harassment. In Study 2, the factor structure of perceptions was explored. In addition, the way in which these perceptions are related to personal variables (i.e. gender role attitudes, self-esteem, and negative affectivity) was investigated. Participants were 353 women currently employed at various organisations. Five factors were identified: sexist hostility, insinuation of interest, sexual hostility, physical sexual offense, and sexual bribery and coercion. Each factor was regressed on the personal variables. After controlling for relevant demographic and organisational variables, gender role attitudes, self-esteem, and negative affectivity predicted sexual harassment perceptions. Specifically, negative affectivity predicted milder forms of harassment, attitudes predicted factors that are considered more severe, and self-esteem predicted all factors but sexist hostility. The extent to which sexual harassment manifestations are universal and how certain manifestations that appeared in the Turkish context broaden the scope of sexual harassment are discussed by referring to the US literature. L'objectif central de cette recherche était l'étude de la perception du harcèlement sexuel au travail en Turquie. Dans une première phase, on a interviewé 53 salariées pour déterminer les comportements relevant du harcèlement sexuel dans ce contexte culturel. Dans une deuxième phase, on a recherché la structure factorielle des perceptions. On a aussi étudié les liens de ces perceptions avec des variables personnelles (Attitudes en rapport avec le rôle découlant du genre, estime de soi et affectivité négative). Les sujets étaient 353 femmes employées dans diverses organisations. Cinq facteurs sont apparus : hostilité sexiste, attirance sous-entendue, hostilité sexuelle, agression sexuelle physique, coercition et corruption sexuelles. Chaque facteur a subi une analyse de régression sur les variables personnelles. En contrôlant de façon appropriée les variables démographiques et organisationnelles, les attitudes en rapport avec le rôle découlant du genre, l'estime de soi et l'affectivité négative prédisent la perception du harcèlement sexuel. En particulier, l'affectivité négative prédit les formes légères de harcèlement, les attitudes prédisent les facteurs considérés comme plus graves et l'estime de soi prédit tous les facteurs sauf l'hostilité sexiste. On discute à partir de la littérature américaine de l'universalité du harcèlement sexuel et du fait que certaines manifestations propres à la Turquie élargissent le champ de ce harcèlement. [source] Higher prevalence of bipolar I disorder among Asian and Latino compared to Caucasian patients receiving treatmentASIA-PACIFIC PSYCHIATRY, Issue 3 2010Sophia H.J. Hwang MSEd Abstract Introduction: There are limited data regarding relationships between race/ethnicity and bipolar disorder. This study assessed such relationships in patients receiving treatment in a university clinic. Methods: Demographic, illness characteristics, symptom severity, treatment, and care utilization data were collected from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation, Mini-International Neuropsychiatric Interview, and the STEP-BD Clinician Rated Packet. Data were compared among 51 Asian, 35 Latino, and 86 Caucasian patients in treatment at the Stanford University Bipolar Disorders Clinic. ,2 tests and analyses of variance were used to assess between-group differences. Results: Asian and Latino compared to Caucasian patients had significantly higher prevalence of bipolar I disorder (58.8% and 60.0% versus 37.2%, respectively). Asian and Latino patients also had a higher prevalence of history of psychosis, but this was related to the excess of bipolar I disorder, becoming non-significant after controlling for bipolar subtype. The racial/ethnic difference in bipolar subtype prevalence did not appear to be secondary to demographic or socioeconomic differences. Discussion: The higher prevalence of bipolar I disorder and thus lower prevalence of bipolar II disorder and bipolar disorder not otherwise specified in Asian and Latino patients may be related to under-diagnosis, misdiagnosis, or care underutilization of patients with milder forms of bipolar disorders. Additional research and public health efforts are warranted to further understand the effects of race and ethnicity on the management of bipolar disorders and to enhance timely and accurate diagnosis, culturally sensitive treatment, and optimal care utilization. [source] Novel treatment of chronic severe hand dermatitis with bexarotene gelBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2004J.M. Hanifin Summary Background Hand dermatitis is an eczematous inflammation of the hands that is related to occupation or to routine activities. It often becomes chronic, and in some patients may become severe and disabling. Topical corticosteroids are effective treatment, particularly for milder forms, but they often lose effectiveness with time and can produce skin atrophy. Objectives To evaluate bexarotene gel topical therapy for safety, tolerability and efficacy in patients with chronic hand dermatitis. Methods A phase I,II open-label randomized clinical study of bexarotene gel, alone and in combination with a low- and a mid-potency steroid, was conducted in 55 patients with chronic severe hand dermatitis at two academic clinics. Results Patients using bexarotene gel monotherapy reached a 79% response rate for ,,50% clinical improvement and a 39% response rate for ,,90% clearance of hands. Adverse events possibly related to treatment in all patients were stinging or burning (15%), flare of dermatitis (16%) and irritation (29%). Thirteen patients (24%) withdrew early, including two for related adverse events and five for inadequate response. Conclusions Bexarotene gel appears to be safe, tolerated by most patients, with useful therapeutic activity in chronic severe hand dermatitis. [source] American Empires: Past and Present,CANADIAN REVIEW OF SOCIOLOGY/REVUE CANADIENNE DE SOCIOLOGIE, Issue 1 2008MICHAEL MANNArticle first published online: 14 JUL 200 L'auteur établit une typologie des empires. Qu'ils soient «directs» ou «indirects», les empires possèdent nécessairement des colonies. Ce n'est pas le cas des empires «informels», mais ceux,ci peuvent être divisés en trois sous-types: les empires «canonniers», «mandataires» et d' «ajustement structurel», à quoi s'ajoute «hégémoniques» comme type de domination non impérial, chaque type tendant à présenter une forme de règles plus douces que le précédent. Les vrais empires sont constitués de différents assortiments de ces règles et, à mesure qu'ils vieillissent, elles tendent à s'alléger. C'est pour cette raison que l'empire américain n'a pas eu de véritable colonie depuis le début du XXe siècle et que des formes plus modérées d'empires informels, après la Deuxième Guerre mondiale, se sont alliées à l'hégémonie. Pourtant, les années 1970 ont connu un plus grand ajustement structurel de l'impérialisme américain alors que les années 1990 et 2000 ont fait face à une tentative d'établissement d'un empire américain canonnier à grande échelle. L'échec de celui-ci menace présentement l'impérialisme américain en général. This paper lays out a typology of empires. "Direct" and "indirect" empires involve colonies. "Informal" empire does not, but can be divided into three subtypes, "gunboats,""proxies," and "structural adjustment.""Hegemony" is added as a nonimperial type of domination. Each tends to be a lighter form of rule than the preceding one. Real empires contain varying mixtures of these and as they age, their rule tends to lighten. Thus in the American empire, there have been no real colonies since the beginning of the twentieth century, and after World War II milder forms of informal empire were blended with hegemony. Yet the 1970s saw an increase in American structural adjustment imperialism, while the 1990s and the 2000s saw an attempt at large-scale American gunboat empire. The failure of the latter is now threatening American imperialism more generally. [source] 4131: Pathologic epithelial and anterior corneal nerve morphology in congenital aniridic keratopathyACTA OPHTHALMOLOGICA, Issue 2010P FAGERHOLM Purpose To document corneal morphology in Swedish families with congenital aniridia. Methods Detailed ophthalmic examinations were conducted in a number of affected and unaffected members. Digital slit lamp photography, anterior segment optical coherence tomography (ASOCT) and in-vivo confocal microscopy (IVCM) examinations were performed bilaterally to document corneal morphology. Results Affected family members presented with different stages of aniridic keratopathy, with a corneal appearance varying from totally transparent to opaque and highly vascularised. Increased corneal thickness in affected members, particularly those with severe keratopathy, was noted by ASOCT. By IVCM, opaque corneas were characterized by active vessels and dense inflammatory cell infiltration. In corneas with milder keratopathy, pathologic epithelial findings included epithelial pleomorphism, focal epithelial opacities, and an absence of limbal epithelial crypts and focal stromal projections at the limbus. Nerves of the anterior cornea exhibited several distinct features, including an unusually close association of subbasal nerves with epithelial cells, an unusually high subbasal nerve density with highly branched nerves, and a prominent whorl region. Additionally, abnormally dense and tortuous anterior stromal nerves, attached to stromal keratocytes, were noted in unaffected members. Conclusion Altered epithelial morphology and a vigorous innervation of the anterior cornea were the most pronounced corneal findings in family members with milder forms of aniridic keratopathy. Further findings confirmed the known increase in corneal thickness and limbal stem cell abnormality in aniridia. [source] De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic featuresCLINICAL GENETICS, Issue 2 2010P Makrythanasis Makrythanasis P, Moix I, Gimelli S, Fluss J, Aliferis K, Antonarakis SE, Morris MA, Béna F, Bottani A. De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features. Loss-of-function mutations of MECP2 are responsible for Rett syndrome (RTT), an X-linked neurodevelopmental disorder affecting mainly girls. The availability of MECP2 testing has led to the identification of such mutations in girls with atypical RTT features and the recognition of milder forms. Furthermore, duplication of the entire gene has recently been described in boys with mental retardation and recurrent infections. We describe a girl with a heterozygous de novo MECP2 duplication. The patient, at the age of 19, has mental retardation with no autistic features. She is friendly but gets frequently anxious. She has neither dysmorphic features nor malformations. Her motor development was delayed with walking at 20 months. Speech is fluid with good pronunciation but is simple and repetitive. Diagnosis was made after single-strand conformation analysis (SSCA) and multiplex ligation-dependent probe amplification (MLPA) analysis of MECP2. Array comparative genomic hybridization (aCGH) analysis showed a duplication of 29 kb including MECP2 and part of IRAK1. Fluorescent in situ hybridization (FISH) has revealed that the duplicated region is inserted near the telomere of the short arm of chromosome 10. X-chromosome inactivation in leukocyte DNA was not skewed. We conclude that it is likely that this MECP2 duplication is responsible for the mental retardation in this patient. This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation. [source] | |||||||||||||