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Clinical Expression (clinical + expression)
Selected AbstractsA7445G mtDNA mutation present in a Portuguese family exhibiting hereditary deafness and palmoplantar keratodermaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2005H Caria ABSTRACT Mitochondrial DNA (mtDNA) A7445G point mutation has been shown to be responsible for familial nonepidermolytic palmoplantar keratoderma (NEPPK) associated with deafness without any additional features. To date, only a few cases have been described. We report a Portuguese pedigree presenting an inherited combination of NEPPK and sensorineural deafness compatible with maternal transmission. Clinical expression and age of onset of NEPPK and deafness were variable. Normal expression patterns of epidermal keratins and filaggrin, intercellular junction proteins including connexin 26, loricrin and cornified envelope proteins, were observed. Molecular analysis revealed that all the affected members, previously screened for Cx26 mutations with negative results, presented the mtDNA A7445G point mutation in the homoplasmic form. To our knowledge, this is the fifth family in whom inherited NEPPK and hearing loss are related to this mitochondrial mutation. [source] Redefining the role of lymphocytes in gastroesophageal reflux disease and eosinophilic esophagitisDISEASES OF THE ESOPHAGUS, Issue 5 2010B. Basseri SUMMARY Eosinophilic esophagitis (EoE) and reflux esophagitis (RE) overlap clinically and histologically. RE is characterized by epithelial infiltration with small numbers of neutrophils and eosinophils, EoE by a prominent eosinophilic infiltrate. Lymphocytic esophagitis (LE), a new entity characterized by peripapillary lymphocytosis, questions the role lymphocytes play in esophageal inflammation. We test the hypothesis that lymphocyte infiltration in RE differs from EoE. One blinded pathologist read esophageal biopsies from 39 RE and 39 EoE patients. Both groups demonstrated significant numbers of lymphocytes (RE 22.7 ± 2.2/HPF, EoE 19.8 ± 1.8/HPF). Eosinophils/HPF in RE and EoE were 2.8 ± 0.7 and 74.9 ± 8.2, respectively (P < 0.001). Neutrophils were uncommon in RE (0.26 ± 0.16/HPF) and EoE (0.09 ± 0.04; P = 0.07). Eight of the 39 RE specimens had ,50 lymphocytes in ,1 HPF. Two were consistent with LE. There was an inverse correlation between numbers of eosinophils and lymphocytes in EoE (R = ,0.47; P = 0.002), and no correlation between them in RE (R = 0.18; P = 0.36). The patients with EoE who used antireflux medications had fewer lymphocytes (16.3 ± 1.3 vs 22.2 ± 2.3/HPF; P = 0.030) and eosinophils (55.6 ± 5.2 vs 76.0 ± 8.7/HPF; P = 0.042) than those who did not. The pathological role of lymphocytes in RE and EoE may be underestimated. Our observation that 5% of the RE specimens meet histopathological criteria for LE potentially blurs the line between these entities. The observation that eosinophil counts are lower in EoE when antireflux meds are used supports the notion that reflux plays a role in the clinical expression of EoE. [source] Doppler Superior Vena Cava Flow Evolution and Respiratory Variation in Superior Vena Cava SyndromeECHOCARDIOGRAPHY, Issue 4 2008Fa Qin Lv M.D. Background: Superior vena cava syndrome (SVCS) is a clinical expression of obstruction of blood flow through the superior vena cava. The patterns of the Doppler flow changes of superior vena cava (SVC), especially the respiratory effects on them have not yet been fully elucidated. This study was to examine SVC Doppler flow patterns and the respiratory effects on them in healthy subjects and patients with SVCS. Methods: The SVC Doppler flow patterns of 18 normal human subjects and 22 patients with SVCS were analyzed at initial diagnosis and were followed up every 2 months for at least 11 months. Results: Among the 22 patients, 5 patients with the tumor near the right atrium oppressing the inferior segment of the SVC had clear VR- and AR-waves, while in the other 17 patients the VR- and AR-waves disappeared or their outlines were vague. The respiratory variations of the S- and D-waves as a percentage change in inspiration compared to expiration in patient group were much lower than those in control group (S-wave: 1.67 ± 3.32% vs. 15.65 ± 16.15%, P = 0.0003; D-wave: 1.80 ± 1.12% vs. 23.55 ± 37%, P = 0.0087), which gradually became larger with treatment and showed no significant difference with those in control group after 7 months. Conclusions: The Doppler flows of the patients with SVCS correlate well with the images of CT scan of them. The respiratory variation of the S- and D-velocities could be used to evaluate the severity of SVC obstruction and its therapeutic effect. [source] Dynamic Variations of Local Cerebral Blood Flow in Maximal Electroshock Seizures in the RatEPILEPSIA, Issue 10 2002Véronique André Summary: ,Purpose: Measurement of cerebral blood flow is routinely used to locate the areas involved in generation and spread of seizures in epilepsy patients. Because the nature of the hyperperfused regions varies with the timing of injection of tracer, in this study, we used a rat model of maximal electroshock seizures to follow up the time-dependent changes in the distribution of seizure-induced cerebral blood flow (CBF) changes. Methods: CBF was measured by the quantitative autoradiographic [14C]iodoantipyrine technique over a 30-s duration. The tracer was injected either at 15 s before seizure induction, simultaneous with the application of the electroshock (tonic phase), at the onset of the clonic phase, or at 3 and 6 min after the seizure (postictal phase). Results: Rates of CBF underwent dynamic changes during the different phases of seizure activity and largely increased over control levels (,400%) in the 45 regions studied during all phases of the seizure (first 3 times). CBF remained higher than control levels in 35 and 15 areas at 3 and 6 min after the seizure, respectively. Conclusions: The distribution of maximal CBF increases showed a good correlation with their known involvement in the circuits underlying the clinical expression of the different types of seizure activity, tonic versus clonic. [source] Molecular imaging in hereditary forms of parkinsonismEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2007M. C. Shih The development of in vivo molecular imaging to evaluate the dopamine (DA) system with positron-emission tomography and single photon emission computed tomography has been of key importance on monitoring in vivo nigrostriatal neuronal loss in Parkinson's disease (PD), mostly through assessments of pre- and post-synaptic DA receptors. The discoveries of genes related to hereditary forms of parkinsonism (PARK1, PARK2, PARK6, PARK7 and PARK8) have increased our understanding either of distinct subtypes of clinical expression in PD or its etiology. This article revises current data on molecular neuroimaging of genetic forms of parkinsonism comparing and contrasting its main features with the classical sporadic forms. Awareness of the spectrum variance in the genotype and its respective PD phenotype are useful to distinguish different pathophysiological mechanisms of PD. [source] Haemophilia and thrombophilia: an unexpected association!HAEMOPHILIA, Issue 4 2004Y. Dargaud Summary., In patients with haemophilia, a close correlation is usually observed between the clinical expression of the disease and plasmatic factor VIII/factor IX clotting activity. However, some patients experience milder bleeding phenotypes than others, although they exhibit a similar biological profile. The high prevalence of some inherited thrombophilia risk factors offers the possibility of a co-inheritance in haemophilic patients which could influence the phenotypic expression of the disease. Rare thrombotic complications occurring in haemophiliacs could also be facilitated by the co-inheritance of modifier genes. The majority of thrombotic events occurring in haemophiliacs are in relation to clotting factor infusions or central venous catheters. Concerning surgical situations, in the absence of therapeutic recommendations, postoperative thromboprophylaxis is not systematically performed in haemophiliacs. However, substitutive treatment more or less completely corrects the coagulation defect and makes the venous thrombosis risk closer to the control population. It should be emphasized that haemophilia does not fully protect against venous thromboembolic disease. Patients with haemophilia very infrequently experience thrombotic events. Thus, the management of thrombotic complications occurring in haemophilic patients should be discussed in each case according to the precipitating risk factors, the clinical context and the thrombo-haemorrhagic balance of the patient with respect to a particular clinical situation. [source] Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype,phenotype relationshipHUMAN MUTATION, Issue 3 2001Niels Gregersen Abstract Mutation analysis of metabolic disorders, such as the fatty acid oxidation defects, offers an additional, and often superior, tool for specific diagnosis compared to traditional enzymatic assays. With the advancement of the structural part of the Human Genome Project and the creation of mutation databases, procedures for convenient and reliable genetic analyses are being developed. The most straightforward application of mutation analysis is to specific diagnoses in suspected patients, particularly in the context of family studies and for prenatal/preimplantation analysis. In addition, from these practical uses emerges the possibility to study genotype,phenotype relationships and investigate the molecular pathogenesis resulting from specific mutations or groups of mutations. In the present review we summarize current knowledge regarding genotype,phenotype relationships in three disorders of mitochondrial fatty acid oxidation: very-long chain acyl-CoA dehydrogenase (VLCAD, also ACADVL), medium-chain acyl-CoA dehydrogenase (MCAD, also ACADM), and short-chain acyl-CoA dehydrogenase (SCAD, also ACADS) deficiencies. On the basis of this knowledge we discuss current understanding of the structural implications of mutation type, as well as the modulating effect of the mitochondrial protein quality control systems, composed of molecular chaperones and intracellular proteases. We propose that the unraveling of the genetic and cellular determinants of the modulating effects of protein quality control systems may help to assess the balance between genetic and environmental factors in the clinical expression of a given mutation. The realization that the effect of the monogene, such as disease-causing mutations in the VLCAD, MCAD, and SCAD genes, may be modified by variations in other genes presages the need for profile analyses of additional genetic variations. The rapid development of mutation detection systems, such as the chip technologies, makes such profile analyses feasible. However, it remains to be seen to what extent mutation analysis will be used for diagnosis of fatty acid oxidation defects and other metabolic disorders. Hum Mutat 18:169,189, 2001. © 2001 Wiley-Liss, Inc. [source] Glutamate and its role in psychiatric illnessHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2001Brendan Belsham Abstract Glutamate, a dicarboxylic amino acid, is the most abundantly active neurotransmitter in the mammalian brain; it is also the principal excitatory neurotransmitter in the cerebral cortex. As our knowledge of this neurotransmitter deepens, it is increasingly being implicated in the pathophysiology of mental illness. This review begins by examining the physiology of glutamate and its receptors. Its role in memory, movement, perception and neuronal development is discussed. The development of the glutamate hypothesis of schizophrenia is traced, and the emerging lines of evidence for attenuated function of the N -methyl- D -aspartate receptor in schizophrenia are examined. For ease of discussion, these are divided into pharmacological, post-mortem, imaging, platelet and genetic studies. Interactions between glutamate and other neurotransmitters are discussed, as are possible mechanisms by which such altered receptor activity might result in the clinical expression of schizophrenia. The possible role of glutamate in major depression and bipolar disorder is explored. The review concludes by highlighting the importance of avoiding a reductionist approach to the pathophysiology of any mental illness. Copyright © 2001 John Wiley & Sons, Ltd. [source] Characteristics of 32 SupercentenariansJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2006Emily A. Schoenhofen BA OBJECTIVES: To report phenotypic characteristics of 32 age-validated supercentenarians. DESIGN: Case series. SETTING: U.S.-based recruitment effort. PARTICIPANTS: Thirty-two supercentenarians. MEASUREMENTS: Multiple forms of proof were used to validate age claims. Sociodemographic, activities of daily living, and medical history data were collected. RESULTS: Age range was 110 to 119. Fifty-nine percent had Barthel Index scores in the partially to totally dependent range, whereas 41% required minimal assistance or were independent. Few subjects had a history of clinically evident vascular-related diseases, including myocardial infarction (n=2, 6%) and stroke (n=4, 13%). Twenty-two percent (n=7) were taking medications for hypertension. Twenty-five percent (n=8) had a history of cancer (all cured). Diabetes mellitus (n=1, 3%) and Parkinson's disease (n=1, 3%) were rare. Osteoporosis (n=14, 44%) and cataract history (n=28, 88%) were common. CONCLUSION: Data collected thus far suggest that supercentenarians markedly delay and even escape clinical expression of vascular disease toward the end of their exceptionally long lives. A surprisingly substantial proportion of these individuals were still functionally independent or required minimal assistance. [source] Modulation of clinical expression of plaque-induced gingivitis: response in aggressive periodontitis subjectsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2 2006Leonardo Trombelli Abstract Aim: The aim of this study was to characterize the gingival inflammatory response to de novo plaque accumulation in subjects treated for aggressive periodontitis (AP). The gingival inflammatory response of the AP subjects was retrospectively compared with that of periodontally healthy individuals (PH) matched for exposure to plaque and of periodontally healthy subjects previously identified as "high responders" (HR) and "low responders" (LR). Materials and Methods: 13 AP subjects and 26 matched PH subjects participated in a 21-day experimental gingivitis trial. Plaque index (PlI), Gingival index (GI), gingival crevicular fluid volume (GCF) and angulated bleeding score (AngBS) were recorded at days 0, 7, 14 and 21. Cumulative plaque exposure (CPE), i.e. PlI over time, was also calculated. Results: GCF was significantly higher in AP compared with PH group at each observation interval (p0.001). In addition, GCF was significantly higher in AP group compared with either LR or HR groups at each observation interval (p<0.001). Conclusions: These results suggest that susceptibility to gingival inflammation in response to de novo plaque accumulation may be related to susceptibility to periodontitis. [source] Psychological profile in oral lichen planusJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2005Kiro Ivanovski Abstract Aim: Oral lichen planus (OLP) is an oral lesion with an enigmatic etiology. To explore the possibility of psycho-somatization, we evaluated the psychological personality profiles of OLP patients. Methods: Twenty patients with reticular; 20 with erosive form of OLP, and 25 controls were tested with the psychological Minnesota Multiphasic Personality Inventory (MMPI)-202 test. Eight clinical scales (hypochondriasis, depression, hysteria, psychopathic deviate, paranoia, psychasthenia, schizophrenia, and hypomania) as well as cortisol level, CD3, CD4, CD8, and CD16 markers by group were compared. Psychosomatization was evaluated by the use of internalization ratio (IR) Index. Results: A characteristic MMPI profile was noted in the OLP groups with high IR index value. Significant differences among the groups were detected for cortisol, CD4, CD8, and CD16 counts. Mean values for hypochondriasis, depression, and hysteria were all significantly different with significantly higher mean scores for both reticular and erosive OLP subjects compared with controls. Conclusions: Prolonged emotive stress in many OLP patients may lead to psychosomatization and may contribute to the initiation and clinical expression of this oral disorder. Clinical significance: If additional research involving a larger and more diverse sample of patients confirms these findings, clinical trials will be needed to determine whether adjunctive psychological intervention provides a benefit in treating patients with OLP. [source] Commentary on cellulite: skin mechanobiology and the waist-to-hip ratioJOURNAL OF COSMETIC DERMATOLOGY, Issue 3 2005Gérald E Piérard Summary Cellulite is a gender-related condition which is the clinical expression of conformational changes taking place in the fibrous strands partitioning the hypodermis. The affected skin areas are those where fat deposition is under the influence of estrogens. Some hypodermal fibrous strands become enlarged and others become loose and look similar to striae distensae. Cellulite is not a result of increased body mass, but its aspect may be influenced by the waist-to-hip ratio. [source] Histopathology of a granulomatous lobular panniculitis in acute Q fever: a case reportJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2010R Soulard Q fever is a zoonotic infection caused by Coxiella burnetii. Two forms of the disease have been described: an acute form with pneumonia, hepatitis or a flu-like syndrome; and a chronic form in which endocarditis is the most frequent clinical expression. We report a 77 year old male with fever and an erythematous nodule on the right leg. Biopsy revealed a granulomatous lobular panniculitis with some granulomas rimmed by an eosinophilic material, giving a "doughnut" or "fibrin-ring" appearance. Q fever serological studies were positive. Cutaneous signs, among them panniculitis, are probably underestimated during the acute phase of the disease, and recognizing different granulomatous patterns may contribute to the diagnosis. Soulard R. Histopathology of a granulomatous lobular panniculitis in acute Q fever: a case report. [source] Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones.JOURNAL OF INTERNAL MEDICINE, Issue 2 2003A population-based study in northern Sweden Abstract., Andersson C, Innala E, Bäckström T (University Hospital, Umeĺ, Sweden). Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in northern Sweden. J Intern Med 2003; 254: 176,183. Objective., To describe the clinical expression of acute intermittent porphyria (AIP) in women, their use of exogenous sex hormones, and the effects on AIP. Design., A retrospective population-based study. Subjects., All women aged ,18 years (n = 190) with DNA-diagnosed AIP in northern Sweden. Results., A total of 166 women (87%) participated; 91 (55%) had manifest AIP. Severe attacks were reported by 82%; 39% reported recurrent premenstrual AIP attacks and 22% reported chronic AIP symptoms. Oral hormonal contraceptives had been used by 58% of all these women and by 50 with manifest AIP (57%). Twelve women (24%) associated oral contraceptives as precipitating AIP attacks; in nine cases their first attack. One woman experienced relief from AIP symptoms. On commencing their treatment, 72% of the women with manifest AIP had not yet suffered their first attack. Twenty-two women (25%) aged ,45 years had used hormonal replacement therapy (HRT) at menopause to remedy climacteric symptoms (the percutaneous route was most frequently used); no AIP attack was precipitated. HRT to remedy vaginal dryness was used by 26 women (28%) aged ,45 years without triggering an AIP attack. Miscarriages were more frequent in women with manifest AIP (50%) than in the latent group (30%, P = 0.014). Conclusions., About half of the women with AIP had used oral hormonal contraceptives. As 25% of women with manifest AIP reported attacks associated with such drugs, caution must still be recommended. Menopausal HRT only rarely affected the disorder. Miscarriage was more common amongst women with manifest AIP. [source] Late solitary metastasis of cutaneous malignant melanoma presenting as abnormal uterine bleedingJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4pt2 2008Massimiliano Fambrini Abstract We present the case of a 52-year-old woman with a history of excised cutaneous malignant melanoma complaining of abnormal uterine bleeding 11 years after initial diagnosis. Hysteroscopic examination showed an endometrial lesion with polypoid shape and endometrial biopsy was suggestive for melanoma. After a complete clinical work-up ruling out other metastatic sites, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Final histopathological and immunohistochemical analysis confirmed the diagnosis of endometrial melanoma with initial myometrial invasion. After a 6-month follow-up period, the patient was disease free. Even after many years of negative follow up, gynecologists should be aware of the possibility that abnormal uterine bleeding could represent the clinical expression of metastatic melanoma in order to offer a prompt diagnosis and a personalized strategy of treatment. [source] Vitamin and trace metal levels in recessive dystrophic epidermolysis bullosaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2004S Ingen-Housz-Oro ABSTRACT Background, In recessive dystrophic epidermolysis bullosa (RDEB), a good nutritional balance is necessary to obtain healing of the chronic wounds. However, involvement of the oral mucosa and oesophagus stenosis may be responsible for severe nutritional deficiencies. Objective, In order to propose an adapted nutritional management, we studied the vitamin and trace metal status of 14 RDEB patients. Methods, Height and weight were measured. Plasma levels of albumin, iron, ferritin, calcium, parathyroid hormone (PTH), folates, vitamins C, D, B12, A, E, B1, B6, PP and B2, zinc, selenium, carnitine and copper were measured. Results, Most patients had a significant growth retardation. We found iron, vitamin D, C, B6, PP, zinc and selenium deficiencies in 36,70% of the patients, without clinical expression, except in one case. Vitamin B1, 12, B2, A/RBP, E/lipids and carnitine were normal. The three patients with gastrostomy feeding had better growth but still a protein deficiency and sometimes vitamin C, B6, PP, zinc and carnitine deficiencies. Conclusion, Vitamin and trace metal deficiencies are frequent in RDEB, even in patients receiving gastrostomy feeding, and often go unrecognized. Regular nutritional evaluation is necessary. Dietary advice and supplements should be given. Enteral feeding by gastrostomy should be discussed in early childhood. [source] Severe hemophilia with mild bleeding phenotype: molecular characterization and global coagulation profileJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2010E. SANTAGOSTINO Summary.,Background: Patients with severe hemophilia may show very varied bleeding tendencies, and the reasons for this heterogeneous clinical expression are unclear. The factor VIII/FIX genotype is the main determinant of the residual factor activity; however, different bleeding phenotypes have also been reported in patients sharing the same mutation. Such global coagulation tests as thrombin generation assays are tools with which to investigate different coagulation profiles among severe hemophiliacs. Objectives, patients and methods: This case,control study was aimed at comprehensively evaluating the role of genotype and endogenous thrombin potential (ETP) as predictors of the clinical phenotype in severe hemophiliacs with an extremely mild bleeding tendency (cases, n = 22), in comparison with those showing a typical bleeding tendency (controls, n = 50). Results: Cases were more frequently affected by hemophilia B than by hemophilia A, and showed a lower incidence of severe FVIII/FIX gene defects (referred to as null mutations), higher FVIII and FIX antigen levels and higher ETP values in platelet-rich plasma than controls (P < 0.05). By multivariate logistic regression, only non-null mutations were confirmed as an independent predictor of a mild clinical phenotype. Conclusions: These results indicate that non-null mutations represent the main determinant of the bleeding tendency, and that ETP measurement in platelet-rich plasma is able to identify severe hemophiliacs with a mild clinical phenotype. [source] Indices of lower airway inflammation in children monosensitized to house dust mite after nasal allergen challengeALLERGY, Issue 10 2008A. Inal Background:, There are few available data assessing the united airway disease and its systemic aspects in children. With this study, we aimed to investigate the inflammation markers of upper and lower airways before and after nasal allergen challenge in mite sensitive children with different clinical expression of the allergic disease. Methods:, Four study groups were formed: rhinitis only, without bronchial hyper-responsiveness (R, n = 10), rhinitis with asthma (R + A, n = 22), atopic asymptomatics (AA, n = 8) and nonallergic healthy controls (C, n = 10). Blood eosinophils, nasal and sputum eosinophils, sputum eosinophil cationic protein (ECP) and cys-LTs, and serum ECP levels were measured before and 24 h after nasal allergen challenge. Results:, The groups were comparable in terms of age and gender. Cumulative symptom scores recorded during and 1 h after nasal challenge were not significantly different between patients with R, R + A and AA groups. At T24, the children belonging to R, R + A and AA showed significant increases in nasal eosinophils (P < 0.01, P < 0.001, and P = 0.01, respectively), sputum eosinophils (P = 0.01, P < 0.001, and P < 0.05, respectively) and blood eosinophils (P < 0.01, P < 0.001, and P < 0.05, respectively). Similarly, increases in sputum ECP (P < 0.01, P < 0.001, and P = 0.07, respectively) and sputum cys-LT levels (P = 0.07, P < 0.001, and P < 0.05, respectively) were detected in children belonging to these three groups at T24. Sputum eosinophils significantly correlated with blood eosinophils (r = 0.54, P < 0.001) and sputum ECP (r = 0.58, P < 0.001) at T24. Conclusions:, This study showed that nasal allergen challenge increased markers of eosinophilic inflammation in both upper and lower airways of children monosensitized to mites, even before the onset of clinical symptoms. [source] Enteric neurodegeneration in ageingNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2008M. Camilleri Abstract, The objective of this article is to review the clinical presentation and neurobiology of degeneration of the enteric nervous system with emphasis on human data where available. Constipation, incontinence and evacuation disorders are frequently encountered in the ageing population. Healthy lower gastrointestinal function is essential for successful ageing as it is critical to maintaining independence and autonomy to pursue further activity. One clinical expression of enteric neurodegeneration is constipation. However, the aetiology may be multifactorial as disturbances of epithelial, muscle or neural function may all result from neurodegeneration. There is evidence of loss of excitatory (e.g. cholinergic) enteric neurons and interstitial cells of Cajal, whereas inhibitory (including nitrergic) neurons appear unaffected. Understanding neurodegeneration in the enteric nervous system is key to developing treatments to reverse it. Neurotrophins have been shown to accelerate colonic transit and relieve constipation in the medium term; they are also implicated in maintenance programmes in adult enteric neurons through a role in antioxidant defence. However, their effects in ageing colon require further study. There is evidence that 5-HT2 and 5-HT4 mechanisms are involved in development, maintenance and survival of enteric neurons. Further research is needed to understand and potentially reverse enteric neurodegeneration. [source] Neuropathological analysis of an asymptomatic adult case with Dandy,Walker variantNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2006G. Notaridis The Dandy-Walker (DW) complex is a rare posterior fossa malformation, usually observed during the prenatal period or the early infancy. Clinically, it is characterized by mental retardation, seizures, cerebellar ataxia as well as symptoms of hydrocephalus. Structural imaging reveal a hypoplasia or agenesis of the cerebellar vermis, enlargement of the fourth ventricle with a posterior fossa cyst. Additional neurodevelopmental changes such as agenesis of the corpus callosum, lissencephaly and cortical dysplasia are also present. We report the first neuropathological analysis of an adult asymptomatic DW case. Brain computerized tomography showed a massive posterior fossa cyst and hypoplasia of the cerebellum. An Ehlers-Danlos syndrome type IV characterized by repetitive intestinal perforations and a saccular aneurysm on the left posterior communicating artery was also present. Macroscopic brain examination revealed hypoplasia of both cerebellar hemispheres and posterior part of the vermis, as well as dilatation of the fourth ventricle without hydrocephalus. The posterior fossa cyst wall was formed by an external arachnoid layer, middle layer with loose connective tissue and an internal layer of ependymal cells. There were two foci of cerebellar cortical dysplasia but no ectopic neurons, neuronal loss or gliosis in both cerebellum and cerebral cortex. No vascular or significant neurodegenerative lesions were observed. In comparison with previous reports in DW infants, this adult case displayed milder brain abnormalities compatible with a diagnosis of DW variant. The preservation of the cortical cytoarchitecture as well as the paucity of additional neurodevelopmental changes may explain the absence of clinical expression. [source] Molecular characterization of sickle cell anemia in the Northern Brazilian state of ParáAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2010Greice De Lemos Cardoso To assess ,+-thalassemia deletion alleles, ,-thalassemia mutations and haplotypes linked to the HBB*S cluster in a sample of 130 unrelated sickle cell anemia (SCA) patients (55% female) from Belém, Pará State, for their possible effects on the patients' survival. -,3.7, -,42, -,20.5, and ,MED ,+-thalassemia deletion alleles were investigated using multiplex gap-PCR method. Characterization of ,-thalassemia mutations was made by direct genomic sequencing of the ,-globin gene amplified through polymerase chain reaction (PCR). Haplotypes were determined by analysis of six polymorphic restriction sites [(1) XmnI-5,,G, (2) HindIII-,G, (3) HindIII-,A, (4) HincII-,,, (5) HincII-3,,,, and (6) HinfI-5,,] followed by restriction digestion and agarose gel electrophoresis. Twenty-one patients (16%) presented -,3.7 thalassemia. Sixteen of those (76%) were heterozygous (-,3.7/,,) and 5 (24%) were homozygous (-,3.7/-,3.7). -,4.2, -,20.5 and ,MED deletions were not found. Nine cases of sickle cell-, thalassemia were found and four different ,-thal mutations were identified: ,+ ,88 (C>T), 3.8%; ,+ codon 24 (T > A), 1.5%; ,+ IVSI-110 (G > A), 0.7% and , (IVSI-1 (G > A), 0.7%. No differences according to age were observed in -,3.7 deletion, ,-thalassemia and HHB*S haplotypes distribution. Our results suggest that although ,- and ,-thalassemia and ,S haplotypes may have modulating effect on clinical expression and hematological parameters of SCA, these genetic variables probably have little influence on the subjects' survival. Am. J. Hum. Biol. 22:573,577, 2010. © 2010 Wiley-Liss, Inc. [source] Serotonin transporter gene polymorphism and psychiatric disorders in NF1 patientsAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 8 2001Frank Bellivier Abstract Neurofibromatosis type 1 (NF1) is an autosomal-dominant genetic disease characterized by a broad clinical expression. Comorbid affective disorders, anxiety disorders, and suicide are frequently observed during NF1. The promoter marker (5-HTTLPR) of the serotonin transporter gene (5-HTT) has been shown to be associated with major affective disorders, anxiety-related trait, and more recently with suicidal behavior. This gene is adjacent to the NF1 gene, raising the question of the implication of the 5-HTT gene in the psychiatric comorbidity during NF1. Eighty-eight patients with NF1 and 184 screened controls were typed for the 5-HTTLPR. No deviation from the Hardy-Weinberg equilibrium in patients was observed. In addition, allele and genotype frequencies were similar in the two groups. Our data do not support the implication of the 5-HTT gene in the psychiatric comorbidities of NF1. © 2001 Wiley-Liss, Inc. [source] Between memory and destiny: Repetition,THE INTERNATIONAL JOURNAL OF PSYCHOANALYSIS, Issue 2 2007NORBERTO CARLOS MARUCCO This essay focuses mainly on the topic of repetition (agieren),on its metapsychological, clinical, and technical conceptions. It contains a core problem, that is, the question of the represented, the nonrepresented, and the unrepresentable in the psyche. This problem, in turn, brings to light the dialectical relation between drive and object and its specific articulation with the traumatic. The author attributes special significance to its clinical expression as ,destiny'. He points out a shift in the theory of the cure from recollection and the unveiling of unconscious desire, to the possibility of understanding ,pure' repetition, which would constitute the very essence of the drive. The author highlights three types of repetition, namely, ,representative' (oedipal) repetition, the repetition of the ,nonrepresented' (narcissistic), which may gain representation, and that of the ,unrepresentable' (sensory impressions, ,lived experiences from primal times,',prelinguistic signifiers,',ungovernable mnemic traces'). The concept-the metaphor-drive embryo brings the author close to the question of the archaic in psychoanalysis, where the repetition in the act would express itself. ,Another unconscious' would zealously conceal the entombed (verschüttet) that we are not yet able to describe-the ,innermost' rather than the ,buried' (untergegangen) or the ,annihilated' (zugrunde gegangen)-through a mechanism whose way of expression is repetition in the act. With ,Constructions in analysis' as its starting point, this paper suggests a different technical implementation from that of the Freudian construction; its main material is what emerges in the present of the transference as the repetition of ,something' lacking as history. The memory of the analytic process offers a historical diachrony whereby a temporality freed from repetition and utterly unique might unfold in the analysis. This diachrony would no longer be the historical reconstruction of material truth, but the construction of something new. The author briefly introduces some aspects of his conception of the psyche and of therapeutic work in terms of what he has designated as psychic zones. These zones are associated with various modes of becoming unconscious, and they coexist with different degrees of prevalence according to the psychopathology. Yet each of them will emerge with unique features in different moments of every analysis, determining both the analyst's positions and the very conditions of the analytic field. The zone of the death drive and of repetition is at the center of this essay. ,Pure' repetition expresses a time halted by the constant reiteration of an atemporal present. In this case, the ,royal road' for the expression of ,that' unconscious will be the act. The analyst's presence and his own drive wager will be pivotal to provide a last attempt at binding that will allow the creation of the lost ,psychic fabric' and the construction, in a conjectural way, of some sort of ,history' that may unravel the entombed (verschüttet) elements that, in these patients' case, come to the surface in the act. The analysand's ,pure' repetition touches, resonates with something of the new unconscious of the analyst. All of this leads the author to underline once again the value of the analyst's self-analysis and reanalysis in searching for connections and especially in differentiating between what belongs to the analyst and what belongs to the analysand. A certain degree of unbinding ensures the preservation of something ungraspable that protects one from the other's appropriation. [source] Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's diseaseANNALS OF NEUROLOGY, Issue 1 2008Nina M. Kemppainen MD Objective The reduced risk for Alzheimer's disease (AD) in high-educated individuals has been proposed to reflect brain cognitive reserve, which would provide more efficient compensatory mechanisms against the underlying pathology, and thus delayed clinical expression. Our aim was to find possible differences in brain amyloid ligand 11C-labeled Pittsburgh Compound B ([11C]PIB) uptake and glucose metabolism in high- and low-educated patients with mild AD. Methods Twelve high-educated and 13 low-educated patients with the same degree of cognitive deterioration were studied with PET using [11C]PIB and 18F-fluorodeoxyglucose as ligands. The between-group differences were analyzed with voxel-based statistical method, and quantitative data were obtained with automated region-of-interest analysis. Results High-educated patients showed increased [11C]PIB uptake in the lateral frontal cortex compared with low-educated patients. Moreover, high-educated patients had significantly lower glucose metabolic rate in the temporoparietal cortical regions compared with low-educated patients. Interpretation Our results suggesting more advanced pathological and functional brain changes in high-educated patients with mild AD are in accordance with the brain cognitive reserve hypothesis and point out the importance of development of reliable markers of underlying AD pathology for early AD diagnostics. Ann Neurol 2007 [source] The selective estrogen receptor , agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: A phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazineARTHRITIS & RHEUMATISM, Issue 2 2010Ronald F. van Vollenhoven Objective Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor , (ER,) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity. Methods A 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding, proof-of-concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28). Results Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial. Conclusion The observed lack of clinical benefit in RA patients treated with an ER, agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ER,-mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs. [source] Macrophage migration inhibitory factor promoter polymorphisms and the clinical expression of sclerodermaARTHRITIS & RHEUMATISM, Issue 11 2006Sou-Pan Wu Objective To investigate the potential association between functional polymorphisms in the gene for the innate mediator, macrophage migration inhibitory factor (MIF), and the clinical expression of systemic sclerosis (SSc). Methods Genomic DNA samples and clinical data were collected from the Scleroderma Family Registry and DNA Repository at the University of Texas Health Science Center at Houston. A total of 740 subjects were studied; 203 of them had diffuse cutaneous SSc (dcSSc), 283 had limited cutaneous SSc (lcSSc), and the remaining 254 healthy subjects served as controls. Association analyses were performed on the whole data set and on patient and sex subsets. Significant relationships were determined between clinical variables and MIF polymorphisms for each disease subtype in the studied groups. Results The frequency of the ,173*C MIF allele, which was previously reported to be associated with high production of MIF, was lower in the lcSSc group (12.6%) than in the dcSSc (19.2%) or control (18.5%) groups (P = 0.010 and P = 0.011, respectively). Haplotype analysis for 2 closely linked polymorphisms in the MIF promoter showed that in white subjects with lcSSc or dcSSc, the lcSSc population had a significantly lower representation of the high-expression MIF haplotype defined by ,173*C and ,794 with 7 CATT repeats (C7) (P = 0.015, odds ratio 1.94 [95% confidence interval 1.14,3.32]). Fibroblasts encoding the C7 MIF haplotype were observed to produce more MIF upon in vitro stimulation than those with a non-C7 haplotype. Conclusion Functional promoter polymorphisms in the MIF gene affect the clinical presentation of SSc. The proinflammatory haplotype defined by C7 is underrepresented in patients with lcSSc. [source] Endothelial nitric oxide synthase gene polymorphisms in giant cell arteritisARTHRITIS & RHEUMATISM, Issue 11 2003Carlo Salvarani Objective To examine potential associations of the Glu/Asp298 polymorphism in exon 7 and the 4a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility to and clinical expression of giant cell arteritis (GCA), particularly in patients with versus those without ischemic complications. Methods Ninety-one consecutive patients with biopsy-proven GCA, who were residents of Reggio Emilia, Italy, and 133 population-based controls from the same geographic area were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for eNOS polymorphisms in exon 7 and intron 4. The patients were separated into 2 subgroups according to the presence or absence of ischemic complications (visual loss and/or jaw claudication and/or aortic arch syndrome). Results The distribution of the Glu/Asp298 genotype differed significantly between GCA patients and controls (corrected P [Pcorr] = 0.003). Carriers of the Asp298 allele (Asp/Asp or Glu/Asp) were significantly more frequent among the GCA patients than among the controls (Pcorr = 0.0002, odds ratio 3.3, 95% confidence interval 1.7,6.3). The distribution of the 4a/b genotype was similar in GCA patients and controls. No significant associations were found when GCA patients with and without ischemic complications were compared. Conclusion Our findings show that the Glu/Asp298 polymorphism of the eNOS gene is associated with GCA susceptibility. [source] Homozygous feature of isolated triphalangeal thumb,preaxial polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotesCLINICAL GENETICS, Issue 1 2009CN Semerci Preaxial polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial polydactyly phenotype. [source] The spectrum of benign myoclonus of early infancy: Clinical and neurophysiologic features in 102 patientsEPILEPSIA, Issue 5 2009Roberto H. Caraballo Summary Purpose:, To redefine benign myoclonus of early infancy (BMEI) through analysis of clinical and neurophysiologic features in 102 patients with the aim to widen the spectrum of the syndrome, including a number of different clinical expressions of transient nonepileptic paroxysmal movements occurring in normal infants. Methods:, We recruited patients from one center in Argentina and two in Italy, including infants with normal neurologic and psychomotor development presenting with brief paroxysmal abnormal movements. Children with motor phenomena occurring only during sleep were excluded. Patients with abnormal interictal or ictal electroencephalography (EEG) findings were also excluded. The follow-up ranged from 2,40 years. Results:, One hundred and two infants (60 male) met the inclusion criteria. Age at onset ranged from 1,12 months, with a median age of 6.2 months. The following nonepileptic paroxysmal motor phenomena were recognized: (1) myoclonus, (2) spasms and brief tonic contractions, (3) shuddering, (4) atonia or negative myoclonus, (5) more than one type of motor phenomenon. In the majority of cases the episodes occurred only while awake and repeated several times a day. In 45 (44.1%) of the 102 cases contractions appeared in clusters. Conclusions:, Based on the analysis of clinical and EMG features in this large series of infants, we postulate that the spectrum of the syndrome is wider than initially suspected, and that the different transient motor manifestations and their correlation with different EMG patterns will allow recognition of this definitely benign condition comprising a variety of episodic motor phenomena in normal babies. [source] | ||||||||||||||||||||||||||||