Full Text Available Two cases of chilblain lupus erythematosus (CLE were seen in females aged 33 years and 18 years. Photosensitivity, chronicity and aggravation in winters were present in both cases. Histopathology revealed follicular keratosis, atrophy and extensive liquefaction of basal cells. Oral pradinisolone with chloroquine resulted in marked improvement in the skin lesions.
Pock, L; Petrovská, P; Becvár, R; Mandys, V; Hercogová, J
A 45-year-old woman had symmetrical livid plaques with yellowish hyperkeratoses for 5 years, which progressed on to the fingers and toes and on the soles of the feet. Two years later creamy, whitish areas and maceration appeared on the buccal mucosa and the lips. A skin biopsy revealed massive collagen hyaline degeneration in the perivascular area, hyperkeratosis and hypergranulosis, small lymphocyte infiltrates with several melanophages and extravasates of erythrocytes in the upper corium in perivascular areas and hydropic degeneration of basal keratinocytes. The findings using direct immunofluorescence were compatible with lupus erythematosus (LE). Laboratory investigation showed a slight leucopenia and thrombopenia, a slightly elevated erythrocyte sedimentation rate, hypocomplementaemia C3 and C4, a high titre of rheumatoid factor and antinuclear antibodies positivity of extractable nuclear antigen. The results reflected probably the development of a systemic form of the disease. The patient was successfully managed by methylprednisolone and hydroxychloroquine. After 1 year of therapy, a new skin biopsy revealed a substantial reduction of hyperkeratosis and hyaline degeneration of collagen tissue in the perivascular areas. The combination of the extensive hyperkeratosis and hyalinization thus seems to be features of the long-lasting, untreated lesions in chilblain LE.
Gordon, Rebecca; Arikian, Anne M; Pakula, Anita S
Chilblains or perniosis is an acrally located cutaneous eruption that occurs with exposure to cold. Chilblains can be classified into primary and secondary forms. The primary or idiopathic form is not associated with an underlying disease and is clinically indistinguishable from the secondary form. The secondary form is associated with an underlying condition such as connective tissue disease, monoclonal gammopathy, cryoglobulinemia, or chronic myelomonocytic leukemia. Histopathology cannot accurately help distinguish the primary from secondary forms of chilblains. This article will raise the awareness of chilblains by presenting two unusual case reports of chilblains in men from Southern California with discussion of the appropriate evaluation and treatment of this condition. Case 1: A 56-year-old Caucasian man presented in January to a Southern California primary care clinic with a report of tingling and burning in both feet, followed by bluish discoloration and swelling as well as blistering. He had no unusual cold exposure prior to the onset of his symptoms. He had a history of "white attacks" in his hands consistent with Raynaud's phenomenon. His symptoms gradually resolved over a 3-week period. Case 2: A 53-year-old Caucasian man also presented to a Southern California clinic in January with a 3-week history of painful tingling in his toes, and subsequent purplish-black discoloration of the toes in both feet. His symptoms occurred 1 week after a skiing trip. He had partial improvement with warming measures. His symptoms resolved 2 weeks after his initial presentation. Chilblains is a relatively uncommon entity in warmer climates but can present during the winter months. Primary care providers in warmer climates such as Southern California in the USA may be unfamiliar with its presentation. It can be diagnosed clinically by the appearance of typical lesions during the cold damp season. Through a thorough history, physical examination and selected laboratory
Rice, Gillian; Newman, William G.; Dean, John; Patrick, Teresa; Parmar, Rekha; Flintoff, Kim; Robins, Peter; Harvey, Scott; Hollis, Thomas; O’Hara, Ann; Herrick, Ariane L.; Bowden, Andrew P.; Perrino, Fred W.; Lindahl, Tomas; Barnes, Deborah E.; Crow, Yanick J.
TREX1 constitutes the major 3′→5′ DNA exonuclease activity measured in mammalian cells. Recently, biallelic mutations in TREX1 have been shown to cause Aicardi-Goutières syndrome at the AGS1 locus. Interestingly, Aicardi-Goutières syndrome shows overlap with systemic lupus erythematosus at both clinical and pathological levels. Here, we report a heterozygous TREX1 mutation causing familial chilblain lupus. Additionally, we describe a de novo heterozygous mutation, affecting a critical catalytic residue in TREX1, that results in typical Aicardi-Goutières syndrome. PMID:17357087
may be idiopathic and self-limited, or associated with systemic diseases. This article discusses the ... systemic diseases, including chronic ... The pathogenesis of perniosis is not ... mation or ulceration. ... venous plexus, and increases in blood.
Ogilvie, W H
Revived interest in sympathetic surgery originated in orthopaedics. Royle's theories and operations. Their trial, failure and final abandonment. Value of sympathetic operations widely investigated; while finality has not been reached they have proved effective for three main purposes: (1) Relief of pain especially in bladder diseases. (2) Removal of inhibition and sphincteric spasm in alimentary, anal and bladder diseases. (3) Production of vaso-dilatation in (a) vaso-spastic diseases; (b) vaso-degenerative diseases; (c) conditions not due to arterial disease in which increased blood supply is beneficial.Poliomyelitis falls into the last group.-Cause of poor blood supply uncertain; ? lack of function; ? upset of some reflex; ? paralysis of vaso-dilators.TWO PROBLEMS ARISE, BOTH OF WHICH MAY BE TREATED BY OPERATIONS ON THE SYMPATHETIC: (1) The cold, blue limb, which develops chilblains, sores, or even deep ulcers every winter, often stopping treatment and requiring patient to be confined to bed. (2) The limb with considerable and rapidly increasing shortening. Sometimes these limbs show a fair return of power, and were it not for the heavy boot made necessary by the shortening, the patient could be made to walk well.Method of attack.-(1) Periarterial sympathectomy; (2) ramisectomy; (3) ganglionectomy. Physiological basis of each. Criticism of (1) and (2).Details of the operation for ganglionectomy.-Alternative approaches and their advantages. The immediate and late results of the procedure.Five cases discussed briefly.
Abdel-Salam, Ghada M H; Miyake, Noriko; Eid, Maha M; Abdel-Hamid, Mohamed S; Hassan, Nihal A; Eid, Ola M; Effat, Laila K; El-Badry, Tarek H; El-Kamah, Ghada Y; El-Darouti, Mohamed; Matsumoto, Naomichi
The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of autosomal recessive disorders, comprising microcephaly, growth retardation, and a skeletal dysplasia. The different types of MOPD have been delineated on the basis of clinical, radiological, and genetic criteria. We describe two brothers, born to healthy, consanguineous parents, with intrauterine and postnatal growth retardation, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA. The sibs had yellowish-gray hair, fair skin, and deficient retinal pigmentation. Skin biopsy showed abnormal melanin function but OCA genes were normal. The older sib had an intracranial hemorrhage at 1 week after birth, the younger developed chilblains-like lesions at the age 2½ years old but analysis of the SAMHD1 and TREX1 genes did not show any mutations. To the best of our knowledge, vasculopathy and pigmentary disorders have not been reported in MOPD I. Copyright © 2011 Wiley Periodicals, Inc.
Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Hassan, Nihal A; Issa, Mahmoud Y; Effat, Laila; Ismail, Samira; Aglan, Mona S; Zaki, Maha S
We describe five patients from three different families with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), which was molecularly confirmed by homozygosity for the g.51G >A and g.55G >A mutations in RNU4ATAC, respectively. The patients showed the classical phenotype and demonstrated in addition variable degrees of gyration abnormalities and malformations of the callosal body with an interhemispheric cyst. One patient also showed underdevelopment of the cerebellar vermis. This confirms that cortical malformations should be considered cardinal manifestations of MOPD I. Oculocutaneous albinism, brain hemorrhage and chilblains have been found to be associated with MOPD I. The present study showed lack of retinal pigmentation in three patients of whom two had an unusually fair complexion of hair and skin. One patient was found to have a hematoma in the left thalamus. This may indicate that both pigmentary abnormalities and vascular anomalies may be part of the phenotype of MOPD I as well. Copyright © 2013 Wiley Periodicals, Inc.
Gray, Elizabeth E; Treuting, Piper M; Woodward, Joshua J; Stetson, Daniel B
Detection of intracellular DNA triggers activation of the stimulator of IFN genes-dependent IFN-stimulatory DNA (ISD) pathway, which is essential for antiviral immune responses. However, chronic activation of this pathway is implicated in autoimmunity. Mutations in TREX1, a 3' repair exonuclease that degrades cytosolic DNA, cause Aicardi-Goutières syndrome and chilblain lupus. Trex1 (-/-) mice develop lethal, IFN-driven autoimmune disease that is dependent on activation of the ISD pathway, but the DNA sensors that detect the endogenous DNA that accumulates in Trex1 (-/-) mice have not been defined. Multiple DNA sensors have been proposed to activate the ISD pathway, including cyclic GMP-AMP synthase (cGAS). In this study, we show that Trex1 (-/-) mice lacking cGAS are completely protected from lethality, exhibit dramatically reduced tissue inflammation, and fail to develop autoantibodies. These findings implicate cGAS as a key driver of autoimmune disease and suggest that cGAS inhibitors may be useful therapeutics for Aicardi-Goutières syndrome and related autoimmune diseases. Copyright © 2015 by The American Association of Immunologists, Inc.
Vallejo, José Ramón; Aparicio Mena, Alfonso J; González, José Antonio
Human urine is currently the subject of biomedical investigations as a potential therapeutic resource and it continues to be used in remedies in different cultures and societies, including the Spanish culture. In this study we gather etnomedical knowledge about urotherapy and determine their associated symbolisms in Spain. A literature overview and a case study were carried out to compile urine-based remedies and as a direct analysis of symbolic systems. Urotherapy is widespread in Spanish folk medicine. Among the 204 collected remedies, those related to treatment of diseases or skin conditions predominate (63%). Remedies have been reported for the treatment of skin diseases such as eczema, chloasma, alopecia, etc. to treat or alleviate burns, chilblains, wounds or skin chapping, and as a treatment of venomous bites. Most of the collected remedies have an associated naturalist symbolism, based on local traditions and the transmission of empirical initial knowledge. The use of urine in Spain is a result of the interaction of two types of practice: a local and traditional urotherapy, rural and with a utilitarian purpose, and a technical urotherapy, limited to an urban environment and a naturopathic medicine.
Lindahl, Tomas; Barnes, Deborah E; Yang, Yun-Gui; Robins, Peter
The major DNA-specific 3'-5' exonuclease of mammalian cells is TREX1 (3' repair exonuclease 1; previously called DNase III). The human enzyme is encoded by a single exon and, like many 3' exonucleases, exists as a homodimer. TREX1 degrades ssDNA (single-stranded DNA) more efficiently than dsDNA (double-stranded DNA), and its catalytic properties are similar to those of Escherichia coli exonuclease X. However, TREX1 is only found in mammals and has an extended C-terminal domain containing a leucine-rich sequence required for its association with the endoplasmic reticulum. In normal S-phase and also in response to genotoxic stress, TREX1 at least partly redistributes to the cell nucleus. In a collaborative project, we have demonstrated TREX1 enzyme deficiency in Aicardi-Goutières syndrome. Subsequently, we have shown that AGS1 cells exhibit chronic ATM (ataxia telangiectasia mutated)-dependent checkpoint activation, and these TREX1-deficient cells accumulate ssDNA fragments of a distinct size generated during DNA replication. Other groups have shown that the syndromes of familial chilblain lupus as well as systemic lupus erythematosus, and the distinct neurovascular disorder retinal vasculopathy with cerebral leukodystrophy, can be caused by dominant mutations at different sites within the TREX1 gene.
G K Singh
Full Text Available Approximately, 140 million people worldwide live permanently at high altitudes (HAs and approximately another 40 million people travel to HA area (HAA every year for reasons of occupation, sports or recreation. In India, whole of Ladakh region, part of Northwest Kashmir, Northern part of Sikkim and Tenga valley of Arunachal are considered inhabited areas of HAA. The low quantity of oxygen, high exposure of ultraviolet (UV light, very low humidity, extreme subzero temperature in winter, high wind velocity, make this region difficult for lowlanders as well as for tourists. Acute mountain sickness, HA pulmonary edema, HA cerebral edema, and thromboembolic conditions are known to occur in HA. However, enough knowledge has not been shared on dermatoses peculiar to this region. Xerosis, UV-related skin disorders (tanning, photomelanosis, acute and chronic sunburn, polymorphic light eruption, chronic actinic dermatitis, actinic cheilitis, etc., cold injuries (frostbite, chilblains, acrocyanosis, erythrocyanosis, etc. nail changes (koilonychias, airborne contact dermatitis, insect bite reaction, and skin carcinoma (basal cell carcinomas, squamous cell carcinomas, and also rarely malignant melanoma are the dermatoses seen in HAAs. Early diagnosis and knowledge of HA dermatoses may prevent serious consequences of disease and improve the quality of life for the visitors as well as for native of the place.
G K Singh
Full Text Available Background : Low humidity, high-velocity wind, excessive ultraviolet (UV exposure, and extreme cold temperature are the main causes of various types of environmental dermatoses in high altitudes. Materials and Methods: A retrospective study was carried out in patients visiting the lone dermatology department in Ladakh between July 2009 and June 2010. The aim was to identify the common environmental dermatoses in high altitudes so that they can be treated easily or prevented. The patients were divided into three demographic groups, namely, lowlanders, Ladakhis (native highlanders, and tourists. Data was analyzed in a tabulated fashion. Results: A total of 1,567 patients with skin ailments were seen, of whom 965 were lowlanders, 512 native Ladakhis, and 90 were tourists. The skin disorders due to UV rays, dry skin, and papular urticaria were common among all groups. The frequency of melasma ( n = 42; 49.4%, chronic actinic dermatitis (CAD ( n = 18; 81.81% of total CAD cases, and actinic cheilitis ( n = 3; 100% was much higher among the native Ladakhis. The frequency of cold-related injuries was much lesser among Ladakhis ( n = 1; 1.19% than lowlanders ( n = 70; 83.33% and tourists ( n = 13; 15.47% ( P < 0.05. Conclusion: Dryness of skin, tanning, acute or chronic sunburn, polymorphic light reaction, CAD, insect bite reactions, chilblain, and frostbite are common environmental dermatoses of high altitudes. Avoidance of frequent application of soap, application of adequate and suitable emollient, use of effective sunscreen, and wearing of protective clothing are important guidelines for skin care in this region.
Giummarra, Melita Joy; Georgiou-Karistianis, Nellie; Nicholls, Michael E R; Gibson, Stephen J; Chou, Michael; Bradshaw, John L
Phantom limb perception is common following amputation, and is sometimes characterised by pain that resembles the characteristics, intensity or location of past pain. We tested Flor's model that phantom pain results from memory for long-lasting znoxious input. We report a questionnaire study of 283 amputees, that explored the experience of painful, non-painful and postural somatosensory memories in the phantom. We explore the impact of pre-amputation pain and impairment duration, and complications in the limb (eg, infection, gangrene, surgery, and vascular disease). Differences in mood, coping and adjustment to amputation are also explored in those with somatosensory pain memories. Our findings support Flor's model, as amputation-related and non-amputation-related pain memories, and non-painful memories comprised pains or sensations that were either enduring/recurring pains or sensations (eg, ingrown toenail, corns, chilblains, arthritis-type pain in winter, night-cramps, or holding a tennis racquet), or resulted from a painful event with a "core-trauma" element (eg, fracture, crushing/penetration injury). Pain memories related to amputation were more common following functional impairment before amputation; infection or surgery prior to amputation; or having diabetic or vascular amputations-which are associated with multiple complications, including neuropathic changes, infection and prior surgery. Furthermore, participants with amputation-related pain memories exhibited higher sensory pain ratings, as well as poorer mood and adjustment to the limitations of amputation. We propose that somatosensory pain memories likely relate to the generation and maintenance of limb representations upon which intense or emotionally powerful past experiences have been imprinted.
Full Text Available The emergence and spread of stress reactions are provided by the blood circulation system. In its turn, the adequacy of blood circulation depends on the hemorheological and vascular mechanisms. The changeability of their properties appears to be the basis of the increasing of stress stages. From the viewpoint of biophysical reactions, any change and movement occur with the expenditure and accumulation of energy. Higher level of adaptation energy waste and secondary level take place, when a small stressor entails a small expenditure. There is a maximum possible rate of adaptive energy consumption and at this maximum the organism cannot cope with any additional stimulus. At the same time adaptive and stress diseases develop. Let’s consider the duration and manifestation of Raynaud's disease from the perspective of adaptation diseases and diseases of the third grade, which appears to be the cause of the double stress effect - cold and emotional- physical and psychic. Total of 97 patients with Raynaud's disease were examined. For a new vision of the problem it was necessary to find out how the streessors of various nature impact the hemoreheological status and vascular resistance. For this purpose all the patients were examined for a resistance index of resistive arteries of the hand and the indices of erythrocyte aggregation and deformability. The patients were divided into four subgroups. The first subgroup – the patients after chilblain, the second subgroup – the patients with psychic strerssor, the third subgroup – the patients with prolonged chronic stress, and the fourth subgroup – the patients without the differentiation of the stressors. According to the obtained results, it is obvious that at cold and emotional stress (I and II subgroups the hemorheological and vascular parameters are changed. However, this change (hemorheological and vascular is more pronounced at chronic emotional stress (III subgroup as compared both to the
Crow, Yanick J; Chase, Diana S; Lowenstein Schmidt, Johanna; Szynkiewicz, Marcin; Forte, Gabriella M A; Gornall, Hannah L; Oojageer, Anthony; Anderson, Beverley; Pizzino, Amy; Helman, Guy; Abdel-Hamid, Mohamed S; Abdel-Salam, Ghada M; Ackroyd, Sam; Aeby, Alec; Agosta, Guillermo; Albin, Catherine; Allon-Shalev, Stavit; Arellano, Montse; Ariaudo, Giada; Aswani, Vijay; Babul-Hirji, Riyana; Baildam, Eileen M; Bahi-Buisson, Nadia; Bailey, Kathryn M; Barnerias, Christine; Barth, Magalie; Battini, Roberta; Beresford, Michael W; Bernard, Geneviève; Bianchi, Marika; Billette de Villemeur, Thierry; Blair, Edward M; Bloom, Miriam; Burlina, Alberto B; Carpanelli, Maria Luisa; Carvalho, Daniel R; Castro-Gago, Manuel; Cavallini, Anna; Cereda, Cristina; Chandler, Kate E; Chitayat, David A; Collins, Abigail E; Sierra Corcoles, Concepcion; Cordeiro, Nuno J V; Crichiutti, Giovanni; Dabydeen, Lyvia; Dale, Russell C; D'Arrigo, Stefano; De Goede, Christian G E L; De Laet, Corinne; De Waele, Liesbeth M H; Denzler, Ines; Desguerre, Isabelle; Devriendt, Koenraad; Di Rocco, Maja; Fahey, Michael C; Fazzi, Elisa; Ferrie, Colin D; Figueiredo, António; Gener, Blanca; Goizet, Cyril; Gowrinathan, Nirmala R; Gowrishankar, Kalpana; Hanrahan, Donncha; Isidor, Bertrand; Kara, Bülent; Khan, Nasaim; King, Mary D; Kirk, Edwin P; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre; Lauffer, Heinz; Laugel, Vincent; La Piana, Roberta; Lim, Ming J; Lin, Jean-Pierre S-M; Linnankivi, Tarja; Mackay, Mark T; Marom, Daphna R; Marques Lourenço, Charles; McKee, Shane A; Moroni, Isabella; Morton, Jenny E V; Moutard, Marie-Laure; Murray, Kevin; Nabbout, Rima; Nampoothiri, Sheela; Nunez-Enamorado, Noemi; Oades, Patrick J; Olivieri, Ivana; Ostergaard, John R; Pérez-Dueñas, Belén; Prendiville, Julie S; Ramesh, Venkateswaran; Rasmussen, Magnhild; Régal, Luc; Ricci, Federica; Rio, Marlène; Rodriguez, Diana; Roubertie, Agathe; Salvatici, Elisabetta; Segers, Karin A; Sinha, Gyanranjan P; Soler, Doriette; Spiegel, Ronen; Stödberg, Tommy I; Straussberg, Rachel; Swoboda, Kathryn J; Suri, Mohnish; Tacke, Uta; Tan, Tiong Y; te Water Naude, Johann; Wee Teik, Keng; Thomas, Maya Mary; Till, Marianne; Tonduti, Davide; Valente, Enza Maria; Van Coster, Rudy Noel; van der Knaap, Marjo S; Vassallo, Grace; Vijzelaar, Raymon; Vogt, Julie; Wallace, Geoffrey B; Wassmer, Evangeline; Webb, Hannah J; Whitehouse, William P; Whitney, Robyn N; Zaki, Maha S; Zuberi, Sameer M; Livingston, John H; Rozenberg, Flore; Lebon, Pierre; Vanderver, Adeline; Orcesi, Simona; Rice, Gillian I
Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutières syndrome-related genes
Full Text Available Abstract Background In the years 2003–2005 research was carried out concerning ethno-medicine in the high Molise (central- southern Italy, a region that has been the object of very little investigation from the ethnobotanical point of view. Upper Molise is a continuation of the mountain profiles of the Abruzzi Appenines: a series of hills, steep slopes and deep fluvial valleys making communications difficult. Primordial traditions (e.g. harvest feasts are typical of the region. Methods Field data were collected through open interviews in the field. These were conducted on both an individual and group level, fresh plants gathered from surrounding areas being displayed. In other cases, individual interviews were conducted by accompanying the person involved to the places where they perform their activities (for example, in the woods with woodcutters, kitchen gardens and fields with housewives, pastures with shepherds, etc.. In total 54 individuals were interviewed. Results Data of 70 taxa belonging to 39 families were gathered. Among the species, 64 are used in human therapy, 5 as insect repellents, 11 in veterinary medicine, 1 to keep eggs and cheeses and 4 for magic purposes. The most important findings in ethno-medicine relate to the lichen Lobaria pulmonaria (L. Hoffm. (wounds and to some vascular plant species: Asplenium trichomanes L. and Ceterach officinarum Willd. (to regularize menstruation, Cyclamen hederifolium (chilblains, Centaurium erythraea Rafn. and Pulmonaria apennina Cristof. & Puppi (bruises, while in the ethno-veterinary field, we have Valeriana officinalis L. (wounds sustained by mules. Also worthy of note, given the isolation of the area, is the number of plants used to protect foodstuffs from parasites, among which Allium sativum L. and Capsicum frutescens L. Conclusion The research revealed a deep-rooted and widespread habit of husbanding the family's resources. Whilst isolation and snowfalls contributed to the widespread
Crow, Yanick J.; Chase, Diana S.; Schmidt, Johanna Lowenstein; Szynkiewicz, Marcin; Forte, Gabriella M.A.; Gornall, Hannah L.; Oojageer, Anthony; Anderson, Beverley; Pizzino, Amy; Helman, Guy; Abdel-Hamid, Mohamed S.; Abdel-Salam, Ghada M.; Ackroyd, Sam; Aeby, Alec; Agosta, Guillermo; Albin, Catherine; Allon-Shalev, Stavit; Arellano, Montse; Ariaudo, Giada; Aswani, Vijay; Babul-Hirji, Riyana; Baildam, Eileen M.; Bahi-Buisson, Nadia; Bailey, Kathryn M.; Barnerias, Christine; Barth, Magalie; Battini, Roberta; Beresford, Michael W.; Bernard, Geneviève; Bianchi, Marika; de Villemeur, Thierry Billette; Blair, Edward M.; Bloom, Miriam; Burlina, Alberto B.; Carpanelli, Maria Luisa; Carvalho, Daniel R.; Castro-Gago, Manuel; Cavallini, Anna; Cereda, Cristina; Chandler, Kate E.; Chitayat, David A.; Collins, Abigail E.; Corcoles, Concepcion Sierra; Cordeiro, Nuno J.V.; Crichiutti, Giovanni; Dabydeen, Lyvia; Dale, Russell C.; D’Arrigo, Stefano; De Goede, Christian G.E.L.; De Laet, Corinne; De Waele, Liesbeth M.H.; Denzler, Ines; Desguerre, Isabelle; Devriendt, Koenraad; Di Rocco, Maja; Fahey, Michael C.; Fazzi, Elisa; Ferrie, Colin D.; Figueiredo, António; Gener, Blanca; Goizet, Cyril; Gowrinathan, Nirmala R.; Gowrishankar, Kalpana; Hanrahan, Donncha; Isidor, Bertrand; Kara, Bülent; Khan, Nasaim; King, Mary D.; Kirk, Edwin P.; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre; Lauffer, Heinz; Laugel, Vincent; La Piana, Roberta; Lim, Ming J.; Lin, Jean-Pierre S.-M.; Linnankivi, Tarja; Mackay, Mark T.; Marom, Daphna R.; Lourenço, Charles Marques; McKee, Shane A.; Moroni, Isabella; Morton, Jenny E.V.; Moutard, Marie-Laure; Murray, Kevin; Nabbout, Rima; Nampoothiri, Sheela; Nunez-Enamorado, Noemi; Oades, Patrick J.; Olivieri, Ivana; Ostergaard, John R.; Pérez-Dueñas, Belén; Prendiville, Julie S.; Ramesh, Venkateswaran; Rasmussen, Magnhild; Régal, Luc; Ricci, Federica; Rio, Marlène; Rodriguez, Diana; Roubertie, Agathe; Salvatici, Elisabetta; Segers, Karin A.; Sinha, Gyanranjan P.; Soler, Doriette; Spiegel, Ronen; Stödberg, Tommy I.; Straussberg, Rachel; Swoboda, Kathryn J.; Suri, Mohnish; Tacke, Uta; Tan, Tiong Y.; Naude, Johann te Water; Teik, Keng Wee; Thomas, Maya Mary; Till, Marianne; Tonduti, Davide; Valente, Enza Maria; Van Coster, Rudy Noel; van der Knaap, Marjo S.; Vassallo, Grace; Vijzelaar, Raymon; Vogt, Julie; Wallace, Geoffrey B.; Wassmer, Evangeline; Webb, Hannah J.; Whitehouse, William P.; Whitney, Robyn N.; Zaki, Maha S.; Zuberi, Sameer M.; Livingston, John H.; Rozenberg, Flore; Lebon, Pierre; Vanderver, Adeline; Orcesi, Simona; Rice, Gillian I.
Aicardi–Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi–Goutières syndrome
Ana Claudia Vieira Martins
Full Text Available This descriptive diagnosis study had the objective to evaluate the functional characteristics and the use of the boots worn by the police officers while they are on duty patrol walking on Florianópolis streets, as well as the influency of the boots in this activity. Selected by not-probabilistic sampling in a casual-systematic way, 234 police officers volunteered to take part in this study. The instrument used was a questionnaire assorted with clarity level of 0.93, validity of 0.85 and reliability of 0.95. According to the results, most police officers have only a pair of boots, which were worn on average 11 hours daily. To the boot usage was attributed the incidence of foot injuries such as callosity, chilblain, embedded nails and blisters. For these police officers the discomforts (overheating, pain and humidity on the feet as well as pain in the body caused by the boot interfered in their work routine taking them to classified their shoes as inappropriate, following the criteria of comfort, safety and durability. Therefore, it was concluded that the boots seemed not to be the ideal shoes in terms of comfort and job performance, because they interfered in their daily routine, causing functional and structural adaptations in the human body during the performance of motor tasks. RESUMO Este estudo descritivo diagnóstico teve como objetivo avaliar as características funcionais e de uso do coturno utilizado pelos policiais militares que realizam a tarefa de locomoção a pé durante as rondas nas ruas de Florianópolis, bem como sua influência nesta atividade. Selecionados por amostragem não-probabilística, casualsistemática por voluntariado, participaram 234 policiais militares. O instrumento utilizado foi um questionário misto com índice de clareza de 0,93, validade de 0,85 e fidedignidade de 0,95. De acordo com os resultados, a maioria dos policiais possui apenas um par de coturnos, permanecendo em média 11 horas diárias com este