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1.
Mol Psychiatry ; 23(3): 569-578, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28727688

RESUMO

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions.


Assuntos
Ansiedade/tratamento farmacológico , Diazepam/farmacologia , Área Tegmentar Ventral/efeitos dos fármacos , Animais , Benzazepinas/farmacologia , Encéfalo/metabolismo , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Masculino , Mitocôndrias/metabolismo , Núcleo Accumbens/metabolismo , Ratos , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Predomínio Social
2.
Reprod Domest Anim ; 52 Suppl 4: 65-68, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29052329

RESUMO

Ion channels play an important role during sperm capacitation allowing the transport through plasma and mitochondrial membranes of specific molecules that are essential for the achievement of this physiologic status. Given that voltage-dependent anion channel 2 (VDAC2) is present in boar spermatozoa and is known to be involved in calcium transport in somatic cells, this study aimed at determining whether it is implicated in sperm capacitation and the acrosome reaction. With this purpose, boar spermatozoa were capacitated in vitro for 4 hr, and acrosome reaction was induced with progesterone for a further hour, with or without the presence of two VDAC2-inhibitors (erastin and olesoxime) at two different concentrations (10 and 100 µM). At different time points (0, 120, 240, 270 and 300 min), an aliquot was taken and sperm motility, membrane integrity and lipid disorder were evaluated using computer-assisted sperm analysis and flow cytometry. The addition of the two inhibitors resulted in opposite effects. While erastin 100 µM reduced the percentage of non-capacitated spermatozoa, the presence of olesoxime at the same concentration prevented the increase in membrane lipid disorder, which is a feature of sperm capacitation. Such prevention was concomitant with a maintaining effect on sperm membrane integrity evaluated through SYBR14/PI. Our results suggest that VDAC2 is involved in the regulation of sperm capacitation, despite the fact that the mechanisms through which erastin and olesoxime act are different.


Assuntos
Capacitação Espermática/efeitos dos fármacos , Suínos , Canal de Ânion 2 Dependente de Voltagem/antagonistas & inibidores , Reação Acrossômica/efeitos dos fármacos , Animais , Colestenonas/farmacologia , Masculino , Lipídeos de Membrana/metabolismo , Piperazinas/farmacologia , Progesterona/farmacologia , Análise do Sêmen , Motilidade dos Espermatozoides , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia
3.
Clin Exp Rheumatol ; 31(1 Suppl 75): S56-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23294518

RESUMO

Large vessel involvement in ANCA-associated vasculitis is very rare. We report here on the case of two patients with ANCA-associated vasculitis and asymptomatic aortic arch involvement diagnosed using FDG-PET/CT. Because aortic involvement in ANCA-associated vasculitis is a potentially life-threatening condition, its early detection can be crucial. FDG-PET/CT may also provide new insights into large vessel involvement as part of the spectrum of ANCA-associated vasculitis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Fluordesoxiglucose F18 , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Corticosteroides/uso terapêutico , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Aortografia/métodos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Nephron Clin Pract ; 115(1): c28-34, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20173347

RESUMO

UNLABELLED: Elderly patients are increasingly enrolled in dialysis programs and present a series of special characteristics due to their high morbidity and mortality. OBJECTIVE: To describe the characteristics of incident dialysis patients aged >75 years, their comorbidities and their admissions, with a view to determining the factors that influence their course and mortality. PATIENTS AND METHODS: The study included all patients aged >75 years who started dialysis in our center since January 2000. The mean duration of follow-up was 3.3 +/- 2.2 years. Data were collected on incident comorbidity, admissions and their causes. A total of 139 patients were included, with a mean age of 78.6 +/- 2.6 years (67.6% males, 33.8% diabetic and 7.9% on peritoneal dialysis). Three groups were established according to age: 75-79, 80-85 and >85 years. The most frequent comorbidities were chronic obstructive pulmonary disease (25.9%), ischemic heart disease (25.2%), heart failure (25.9%), neoplasms (23.7%), peripheral vascular disease (23.7%), cerebrovascular disease (18.7%) and arterial hypertension (81%). The Charlson index was calculated, not adjusted for age, and comorbidity tertiles were established. RESULTS: During follow-up, the patients presented 0.82 +/- 0.99 admissions/patient/year, with a duration of 12.1 +/- 20.6 days/patient/year. The main causes of admission were infection (33%), vascular access problems (27%) and peripheral vascular events (14%). A total of 61 patients died (44%), and 4 underwent kidney transplantation (2.9%). The mean duration of follow-up of the transplanted patients was 3.6 +/- 1.8 years. The main causes of death were infection (32%), cardiovascular problems (28.3%) and neoplastic disease (11.3%). The global survival rate was 90, 82 and 53% after 1, 2 and 5 years, respectively. No significant differences in survival or annual admission rate were found in relation to age group and dialysis technique. In contrast, the annual admission rate and days of admission were directly correlated to the Charlson index (p = 0.009 and p = 0.032, respectively). No significant differences in the Charlson index were found between the patients on hemodialysis and those subjected to peritoneal dialysis. In the univariate model, the factors associated to mortality were diabetes, chronic obstructive pulmonary disease, heart failure and the Charlson index. In the multivariate model, only the Charlson index remained as an independent predictive factor (p = 0.006). CONCLUSIONS: Unlike the general population, age does not influence mortality or admissions in elderly patients on dialysis. Incident comorbidity is the factor exerting the greatest influence upon mortality and admissions. Advanced age in itself should not be regarded as an excluding factor for starting dialysis.


Assuntos
Doenças Cardiovasculares/mortalidade , Transtornos Cerebrovasculares/mortalidade , Doença Pulmonar Obstrutiva Crônica/mortalidade , Diálise Renal/mortalidade , Análise de Sobrevida , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Incidência , Masculino , Medição de Risco/métodos , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida
5.
Dermatology ; 221(2): 113-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20523032

RESUMO

X-linked ichthyosis (XLI) is a relatively common keratinization disorder which is caused, in the vast majority of cases, by a total deletion of the sulfatase steroid (STS) gene. Dystrophic epidermolysis bullosa (DEB) is a scarring form of epidermolysis bullosa of either autosomal recessive or dominant inheritance secondary to collagen VII gene mutations. We report the first case of a patient with both XLI and DEB in whom a partial deletion of the STS gene and a recessive point mutation in COL7A1 were demonstrated.


Assuntos
Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica/genética , Ictiose Ligada ao Cromossomo X/genética , Esteril-Sulfatase/genética , Criança , Comorbidade , Humanos , Masculino , Mutação Puntual , Deleção de Sequência
6.
Rev Esp Enferm Dig ; 102(7): 413-20, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20617861

RESUMO

OBJECTIVES: To evaluate the diagnostic yield of endoscopic ultrasonography in loco-regional staging of gastric cancer in our medium and to determine the impact of this technique on later therapeutic management. MATERIAL AND METHODS: This is a retrospective study carried out on patients histologically diagnosed with gastric adenocarcinoma who had been referred for endoscopic ultrasonographic examination. The technique results were compared with those obtained from surgical samples and/or from exploratory laparoscopy- laparotomy. We compared the initial therapeutic decision based on conventional diagnostic techniques with the final therapeutic management based on the endoscopic ultrasonography results. RESULTS: Forty-six patients with gastric adenocarcinoma were included in the study (a reference exploration was available in 36 cases). Diagnostic precision was 70% in stage T, while in stages T1, T2, T3 y T4 was 100, 38, 82, and 100%, respectively. The sensitivity and specificity to differentiate T1-2 from T3-4 was 94 and 85%, respectively. We could not identify factors associated with obtaining a correct diagnosis in staging T. Diagnostic precision was 72% for stage N (N0: 58%; Nx 88%). The presence of free perigastric fluid was identified in 7 cases; the presence of peritoneal carcinomatosis was later confirmed in 5 of these. The result of endoscopic ultrasonography led to a modification in the subsequent therapeutic management in 13 patients (28%). CONCLUSIONS: Endoscopic ultrasonography is a useful technique for loco-regional staging of gastric adenocarcinoma, which may have important implications in the therapeutic management of these patients.


Assuntos
Endossonografia , Cuidados Pré-Operatórios , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/terapia
7.
Rev Med Interne ; 41(12): 800-808, 2020 Dec.
Artigo em Francês | MEDLINE | ID: mdl-32861532

RESUMO

PURPOSE: To describe a case series of patients investigated in internal medicine for orbital inflammation (OI) since the individualization of the clinical entity of the IgG4-related orbital disease (IgG4 ROD). PATIENTS AND METHODS: Thirty four patients were consecutively referred by a specialized center where orbital biopsy was performed when the lesion was surgically accessible. Fourteen patients were excluded in case of missing data or lymphoma, periocular xanthogranuloma or Graves' orbitopathy. Patients with systemic or auto-immune disease according to the international criteria, or presenting with idiopathic orbital inflammation syndrome (IOIS), were included. Knowing the histological similarities between IOIS and IgG4 ROD, immunohistochemical assessment of plasma cells for IgG4 positivity was performed for every patient with available biopsy. Clinical and biological characteristics, treatment and response to treatment of included patients are reported. RESULTS: Among 22 included patients, 10 presented with orbital manifestation of a systemic or autoimmune disease including 2 sarcoidosis (9%) and 8 (36%) cases of non specific OI which were reclassified in IgG4 ROD. Finally, IOIS of various clinicopathological presentation was diagnosed for 12 patients including 10 with histological documentation. Whereas relapse and resistance were not found to be related to IgG4 positivity (50% in both IOIS and IgG4 ROD groups), another treatment in addition to corticosteroids was more often necessary in IgG4 ROD patients (50%) than in IOIS patients (25%). CONCLUSION: After ruling out auto-immune orbital diseases, especially IgG4 ROD, IOIS should be discussed. Factors conditioning the corticosteroid response are yet to be determined.


Assuntos
Inflamação/terapia , Doenças Orbitárias/terapia , Adulto , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/patologia , Doenças Autoimunes/terapia , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Medicina Interna , Masculino , Pessoa de Meia-Idade , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/patologia , Pseudotumor Orbitário/diagnóstico , Pseudotumor Orbitário/patologia , Pseudotumor Orbitário/terapia , Estudos Retrospectivos , Síndrome , Adulto Jovem
8.
Transfus Med ; 19(4): 189-94, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19708860

RESUMO

Assessment of the quality of donor selection and safety of the blood supply can be estimated by monitoring the prevalence of the serologic markers of infectious disease in screening tests. In the present study, changes in rates of hepatitis B virus (HBV) infection are studied in the period 1998-2007 in Iranian Blood Transfusion Organization (IBTO). Prevalence of serological marker of HBV infection [hepatitis B surface antigen (HBsAg)] was evaluated in blood donations in Iran as well as for Fars province representing a low prevalence, and Sistan-Baluchestan (S&B) province as a high prevalence region throughout 1998-2007. For assessing frequency of infection, the prevalence of HBsAg per 100 000 donations and 95% confidential intervals (95% CIs) is calculated. P value is estimated by chi(2) test. A total of 14 599 783 donations were collected during 10 years. The overall HBsAg prevalence rates declined from a 1.79% (1789/100 000 donations) in 1998 to 0.41% (409/100 000 donations) in 2007 in Iran. In Fars province, HBsAg prevalence decreased from 0.89% in 92 999 donations in 1998 to 0.34% in 148 014 donations in 2007 and in S&B province, the rate of HBsAg has gone down from 3.74% in 44 036 donations in 1998 to 1.15% in 56 057 donations in 2007. The frequency of HBV infection entering the blood supply has decreased over this period as a result of improvement in donor recruitment and selection, usage of software in transfusion services and possibly decreasing HBV infection prevalence in general population.


Assuntos
Doadores de Sangue , Vírus da Hepatite B , Hepatite B/epidemiologia , Biomarcadores/sangue , Seleção do Doador , Feminino , Hepatite B/sangue , Hepatite B/prevenção & controle , Hepatite B/transmissão , Antígenos da Hepatite B/sangue , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Prevalência , Estudos Retrospectivos
9.
Rev Med Interne ; 30(6): 492-500, 2009 Jun.
Artigo em Francês | MEDLINE | ID: mdl-18824279

RESUMO

In developed countries, uveitis is quite common and chronic course is associated with a poor visual prognosis. However, no guidelines for their management have been consensually proposed. Based on the experience of ophthalmologists and internists from tertiary care centers, this article describes the management of uveitis, including the diagnostic procedure, indications and types of anti-inflammatory treatments. We focus on the interest of an exhaustive ophthalmologic examination for the diagnosis of an underlying systemic disease such as sarcoidosis. In this way, a multidisciplinary staff could be useful for an optimal management of uveitis. We also reviewed the main current treatments for severe uveitis. Whatever the origin of ocular inflammation, corticosteroids are consensually used as first line treatment. However, the identification of an underlying systemic disease helps in the refinement of further therapeutic choices. In cases of refractory and sight threatening uveitis, the short-term use of infliximab, a chimeric anti-TNF-alpha antibody, has been shown to be effective and safe. These recommendations do not constitute treatment guidelines but aim at improving the uniformity of clinical practice for the management of uveitis, until higher levels of evidence are obtained.


Assuntos
Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Algoritmos , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Infliximab , Medicina Interna , Papel do Médico , Uveíte/etiologia
10.
J Fr Ophtalmol ; 42(3): 303-321, 2019 Mar.
Artigo em Francês | MEDLINE | ID: mdl-30850198

RESUMO

Sarcoidosis is a systemic granulomatosis characterized by the formation of epithelioid and giant cell granulomas without caseous necrosis. To make the diagnosis, it is necessary to prove systemic granulomatosis involving at least two organs; but in practice, a combination of clinical, paraclinical and histologic findings is used. It affects predominantly women with a bimodal age distribution: 25-29years and 65-69years. The most commonly affected organs are the mediastinal lymphatic system, lungs, skin and eyes. Ophthalmological involvement is present in 20 to 50% of cases. The typical ocular presentation is that of granulomatous uveitis associated with venous retinal vasculitis and lesions of peripheral multifocal choroiditis. This ophthalmological presentation, although very evocative, is not always associated with systemic disease. The diagnosis of ocular sarcoidosis is then presumed in the absence of histological evidence. Algorithms combining ophthalmological and systemic signs have been proposed in cases of isolated uveitis. They make it possible to establish the diagnosis of ocular sarcoidosis with various levels of probability. The absence of significant granulomas on a systemic level during primary ocular involvement remains the main hypothesis to explain these diagnostic difficulties. Treatment is well described, as the uveitis of sarcoidosis is most often steroid responsive. In the case of corticosteroid-dependent uveitis, the first-line immunosuppressant remains methotrexate. The use of anti-tumor necrosis factor-alpha is an interesting alternative in patients whose ocular sarcoidosis is refractory to conventional immunosuppressants.


Assuntos
Sarcoidose , Adulto , Distribuição por Idade , Idoso , Corioidite/diagnóstico , Corioidite/epidemiologia , Diagnóstico Diferencial , Técnicas de Diagnóstico Oftalmológico , Endoftalmite/diagnóstico , Endoftalmite/epidemiologia , Granuloma/diagnóstico , Granuloma/epidemiologia , Humanos , Coroidite Multifocal , Vasculite Retiniana/diagnóstico , Vasculite Retiniana/epidemiologia , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Sarcoidose/patologia , Uveíte/diagnóstico , Uveíte/epidemiologia
11.
Rev Med Interne ; 40(4): 255-257, 2019 Apr.
Artigo em Francês | MEDLINE | ID: mdl-30616928

RESUMO

INTRODUCTION: Acute muscle involvement is an infrequent complication of corticosteroids, characterized by muscle weakness and a rhabdomyolysis, rapidly regressive after withdrawal of corticosteroids. CASE REPORT: We report the case of a woman admitted in intensive care unit for acute severe asthma, treated with high doses of methylprednisolone. Serum CPK level raised with a peak at 28,160 UI/L (n<250 UI/L) at day 15, suggesting acute rhabdomyolysis with renal failure. CPK rapidly normalized when corticosteroids were discontinued. Other causes of rhabdomyolysis were ruled out. CONCLUSION: This necrosing myopathy under high doses of corticosteroids has been described in patients with severe acute asthma. The mechanism of the muscle damage results from a combination of corticosteroids toxicity, respiratory acidosis and mechanic ventilation.


Assuntos
Corticosteroides/efeitos adversos , Asma/tratamento farmacológico , Rabdomiólise/induzido quimicamente , Doença Aguda , Corticosteroides/uso terapêutico , Asma/patologia , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Rabdomiólise/diagnóstico , Índice de Gravidade de Doença
12.
Rev Med Interne ; 40(7): 419-426, 2019 Jul.
Artigo em Francês | MEDLINE | ID: mdl-30871866

RESUMO

INTRODUCTION: Though several assessment tools for resident professional skills based on workplace direct observation have been validated, they remain scarcely used in France. The objective of this study was to evaluate the reliability and the validity of a workbook including several assessment forms for different components of the professional competency. METHODS: Three assessment forms have been tested over a period of 6 months in a multicentric study including 12 French internal medicine departments: the French version of the mini-CEX, an interpersonal skills assessment form (OD_CR) and the multisource feedback form (E_360). Reliability has been assess using the intra-class correlation coefficient (ICC) and the Cronbach alpha coefficient. Arguments for validity have been provided looking at the ability of the forms to detect an increase in the scores over time and according to the level of experience of the resident. RESULTS: Twenty-five residents have been included. The Cronbach alpha was of 0.90 (n=70) with the mini-CEX, 0.89 with the OD_CR (n=62) and 0.77 with the E_360 (n=86). ICC showed a wide variation according to the items of the mini-CEX and the OD-CR probably due to the poor number of observations performed by residents. The scores of most of the items of these two forms increased between M1 and M6. The scores of the E_360 were high: 7.3±0.8 to 8.3±2.4 (maximum 9) and did not vary according to the level of experience. CONCLUSION: This study suggest that it would be difficult to ensure a sufficient reliability for professional skills assessment using these tools given our available current human and material resources. However, these assessment forms could be added to the resident portfolio as supports for the debriefing in order to document their progression during their formation.


Assuntos
Avaliação Educacional/métodos , Medicina Interna/educação , Internato e Residência , Competência Clínica , Avaliação Educacional/normas , Escolaridade , França , Humanos , Medicina Interna/normas , Internato e Residência/normas , Estudos Prospectivos , Padrões de Referência , Reprodutibilidade dos Testes , Projetos de Pesquisa , Estudantes de Medicina/estatística & dados numéricos
13.
Nefrologia ; 28(3): 311-6, 2008.
Artigo em Espanhol | MEDLINE | ID: mdl-18590498

RESUMO

Peripheral vascular disease (PVD) is a common disease among patients undergoing hemodialysis leading to increase morbidity and mortality with a high risk of inflammation and sepsis. The aim of the present study was to determinate PVD prevalence in our hemodialysis population and association with inflammation. The study sample consisted of 220 patients prevalents in hemodialysis. A basal study was made in 2001 and a follow up for 47 months. Data were collected retrospectively. PVD diagnosis was made attending to limb pulses and doppler in revisions. Diagnosis was classified as rest pain, ischemic ulceration and gangrene. Among a total of 220 patients, 89 had prevalent PVD. Thirty per cent had rest pain, 6,5% had ischemic ulceration and 3% had gangrene. Ninety five per cent underwent medical treatment, 0,5% were treated by percutaneous transluminal angioplasty (PTA), 2% were treated with surgical revascularization and 2,5% were treated with amputation. Patients with PVD were older, with higher Charlson index, diabetes, they hay higher CRP and fibrinogen serum levels; and lower albumin and prealbumine serum levels. Survival PVD was decreased in Kaplan-Meier (log rank =12,4; p<0,000). Adjusted Cox regression analysis revealed that PVD (p =0,034; OR =2,10; IC [1,06 ; 4,23]) ; age (p =0,001; OR =1,06; IC [1,03 ; 1,09]) and low serum albumin levels (p =0,012; OR =0,93; IC [0,89 ; 0,98]) predicted significantly the risk of mortality. PVD is an independent mortality risk factor in hemodialysis patients. An early diagnosis and treatment are able with examination and doppler. In our sample, a few patients are treated with PTA or surgical revascularization. There is an association between PVD and inflammation.


Assuntos
Doenças Vasculares Periféricas , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/epidemiologia , Doenças Vasculares Periféricas/etiologia , Doenças Vasculares Periféricas/mortalidade , Prevalência , Diálise Renal/efeitos adversos , Estudos Retrospectivos
14.
J Fr Ophtalmol ; 41(10): e451-e467, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30449643

RESUMO

Sarcoidosis is a systemic granulomatosis characterized by the formation of epithelioid and giant cell granulomas without caseous necrosis. To make the diagnosis, it is necessary to prove systemic granulomatosis involving at least two organs; but in practice, a combination of clinical, paraclinical and histologic findings is used. It affects predominantly women with a bimodal age distribution: 25-29 years and 65-69 years. The most commonly affected organs are the mediastinal lymphatic system, lungs, skin and eyes. Ophthalmological involvement is present in 20 to 50% of cases. The typical ocular presentation is that of granulomatous uveitis associated with venous retinal vasculitis and lesions of peripheral multifocal choroiditis. This ophthalmological presentation, although very evocative, is not always associated with systemic disease. The diagnosis of ocular sarcoidosis is then presumed in the absence of histological evidence. Algorithms combining ophthalmological and systemic signs have been proposed in cases of isolated uveitis. They make it possible to establish the diagnosis of ocular sarcoidosis with various levels of probability. The absence of significant granulomas on a systemic level during primary ocular involvement remains the main hypothesis to explain these diagnostic difficulties. Treatment is well described, as the uveitis of sarcoidosis is most often steroid responsive. In the case of corticosteroid-dependent uveitis, the first-line immunosuppressant remains methotrexate. The use of anti-tumor necrosis factor alpha is an interesting alternative in patients whose ocular sarcoidosis is refractory to conventional immunosuppressants.


Assuntos
Sarcoidose , Adulto , Idoso , Diagnóstico Diferencial , Técnicas de Diagnóstico Oftalmológico , Oftalmopatias/diagnóstico , Oftalmopatias/epidemiologia , Oftalmopatias/etiologia , Oftalmopatias/terapia , Feminino , Humanos , Masculino , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Sarcoidose/etiologia , Sarcoidose/terapia
15.
Neurologia (Engl Ed) ; 33(1): 47-58, 2018.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25976937

RESUMO

INTRODUCTION: Alzheimer disease (AD) is a major neurodegenerative disorder which eventually results in total intellectual disability. The high global prevalence and the socioeconomic burden associated with the disease pose major challenges for public health in the 21st century. In this review we focus on both existing treatments and the therapies being developed, which principally target the ß-amyloid protein. DISCUSSION: The amyloidogenic hypothesis proposes that ß-amyloid plays a key role in AD. Several pharmacological approaches aim to reduce the formation of ß-amyloid peptides by inhibiting the ß-secretase and γ-secretase enzymes. In addition, both passive and active immunotherapies have been developed for the purpose of inhibiting ß-amyloid peptide aggregation. CONCLUSIONS: Progress in identifying the molecular basis of AD may provide better models for understanding the causes of this neurodegenerative disease. The lack of efficacy of solanezumab (a humanised monoclonal antibody that promotes ß-amyloid clearance in the brain), demonstrated by 2 recent Phase III clinical trials in patients with mild AD, suggests that the amyloidogenic hypothesis needs to be revised.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide , Secretases da Proteína Precursora do Amiloide/metabolismo , Anticorpos Monoclonais Humanizados , Humanos
16.
Rev Med Interne ; 39(9): 746-754, 2018 Sep.
Artigo em Francês | MEDLINE | ID: mdl-29398045

RESUMO

Inflammatory orbitopathies relate to an inflammatory state originating within the orbit and its adnexes, except the inner ocular globe. Orbital inflammation (OI) may be either localized manifestation of a proven or like autoimmune disease, or local response from immune system against infectious, structural or tumoral antigens. We review the clinical manifestations of OI, which provide helpful clues to the diagnosis and describe the inflammatory, infectious and neoplastic conditions classically associated with OI. Autoimmune diseases are probably the most common causes of OI associated with a bilateral dacryoadenitis (e.g., sarcoidosis, granulomatosis with polyangiitis, IgG4-related disease). We focused on a major part of the IgG4-RD spectrum, the IgG4-related orbital disease which has been recently described and the idiopathic orbital inflammation syndrome that one should consider in patients 40 years of age or older with non specific inflammation OI on biopsy but without underlying local or systemic disease. An algorithm for the diagnostic approach of OI was proposed. If systemic explorations fail to diagnose an underlying disease, histopathologic control is required for distinguishing non-specific OI from other differential diagnosis, especially lymphoma. In the cases of pure myositic locations and posteriorly located tumours where biopsy could damage to the optic nerve, analysis of orbital lesions in T2W IRM sequence may be helpful to distinguish idiopathic OI (IOI) from lymphoma. When the diagnostic work-up fails, a corticosteroid trial could be used, but its beneficial effect has to be cautiously interpretated before definitively diagnosing IOI. Finally, treatments used in main infllammatory orbitopathies were also reviewed.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Conhecimentos, Atitudes e Prática em Saúde , Inflamação/diagnóstico , Medicina Interna/métodos , Doenças Orbitárias/diagnóstico , Médicos , Algoritmos , Diagnóstico Diferencial , Humanos , Inflamação/complicações , Inflamação/etiologia , Inflamação/terapia , Doenças Orbitárias/complicações , Doenças Orbitárias/etiologia , Doenças Orbitárias/terapia
17.
Rev Med Interne ; 39(9): 755-764, 2018 Sep.
Artigo em Francês | MEDLINE | ID: mdl-29891262

RESUMO

Despite extensive investigations, including the use of Interferon-gamma release assays (IGRA), the diagnosis of intraocular tuberculosis (TB) remains challenging. Ocular evidence of Mycobacterium tuberculosis in low endemic countries for TB is extremely rare, leading mostly to a TB-related ocular inflammation presumptive diagnosis. This present work aims: to highlights the main clinical patterns suggestive of ocular TB; and the latest recommended guidelines for diagnosing ocular TB to clarify interferon-gamma release assay (IGRA) contribution and accuracy to the management of intraocular TB and its diagnosis, in addition to other available diagnostic tools, such as tuberculin skin test, bacteriologic and histologic analysis from intra/extra ocular sample and radiographic investigations; to define the accuracy of these diagnostic tools according to the endemic TB prevalence; and finally to identify therapeutic strategies adapted to the main clinical presentations of ocular TB. Our review of the literature shows that management of suspected ocular TB differs significantly based on whether patients are from high or low TB prevalence countries since accuracy of chest X-ray, tuberculin skin test and IGRA is significantly different. Taking into account these discrepancies, distinct guidelines should be determined for managing patients with suspected ocular TB, taking into consideration home prevalence of TB-patients.


Assuntos
Tuberculose Ocular , Diagnóstico Diferencial , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Teste Tuberculínico , Tuberculose Ocular/diagnóstico , Tuberculose Ocular/epidemiologia , Tuberculose Ocular/patologia , Tuberculose Ocular/terapia
18.
Rev Med Interne ; 39(9): 711-720, 2018 Sep.
Artigo em Francês | MEDLINE | ID: mdl-29496270

RESUMO

Scleritis is an inflammatory disease of the sclera; outer tunic of the eye on which the oculomotor muscles are inserted. It can be associated with a systemic disease up to one time out of 3. These associated diseases are mainly rheumatoid arthritis, vasculitis, including granulomatosis with polyangiitis in the first line and spondyloarthropathies. Before mentioning such an etiology, it is necessary to eliminate an infectious cause, mainly herpetic, which is regularly underestimated. The classification of scleritis is clinical. We distinguish between anterior scleritis and posterior scleritis. Anterior scleritis is diffuse or nodular, usually of good prognosis. Anterior necrotizing scleritis with inflammation is often associated with an autoimmune disease, necrotizing scleritis without inflammation usually reflects advanced rheumatoid arthritis. The treatment of these conditions requires close collaboration between internists and ophthalmologists to decide on the use of corticosteroid therapy with or without immunosuppressors or biotherapies.


Assuntos
Doenças Autoimunes , Conhecimentos, Atitudes e Prática em Saúde , Inflamação , Medicina Interna/métodos , Médicos , Esclerite , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Técnicas de Diagnóstico Oftalmológico , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Inflamação/terapia , Esclerite/diagnóstico , Esclerite/etiologia , Vasculite/complicações , Vasculite/diagnóstico , Vasculite/terapia
19.
Rev Med Interne ; 39(9): 687-698, 2018 Sep.
Artigo em Francês | MEDLINE | ID: mdl-29610003

RESUMO

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).


Assuntos
Guias de Prática Clínica como Assunto , Uveíte/terapia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Terapia Biológica/métodos , Prova Pericial , Humanos , Imunossupressores/uso terapêutico , Guias de Prática Clínica como Assunto/normas , Fator de Necrose Tumoral alfa/imunologia
20.
Nutr Hosp ; 21(5): 567-72, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-17044602

RESUMO

OBJECTIVES: Bariatric surgery has demonstrated its efficacy in weight loss and in reducing the comorbidities in the morbid obesity patient. The objectives of this study were to analyze the effectiveness and complication of the Scopinaro and gastric bypass techniques as well as the results from open surgery verses laparoscopy. DESIGN: Retrospective study from 1999-2005. SUBJECT AND METHODS: 78 patients with morbid obesity were operated. 50 patients underwent open surgery and 28 underwent laparoscopy. Gastric bypass was performed in 54 patients, Scopinaro was performed in 20 patients and Vertical Banded Gastroplasty (VBG) was performed in 3 patients. The follow up time was between 6 and 60 months. The results obtained with Scopinaro and gastric bypass were compared as well as the results from open surgery verses laparoscopy. RESULTS: The percentage of patients with a percent of excess weight loss under 50% in two years was of 5% and 13%, and the excess weight loss over 75% was of 55% ad 40% in the gastric bypass and the Scopinaro technique respectively. All the comorbidities improved. The average stay was decreased in the case of laparoscopy. The non-nutritional complications were increased for most cases in open surgery with the emphasis in eventrations, infections of the wound and respiratory complications. The nutritional complications were superior with Scopinaro's technique. CONCLUSIONS: Based on our study, we would recommend the performance of gastric bypass for laparoscopy due to the reduced average stay and less nutritional and surgical complications. The literature results vary and therefore we consider necessary further control and random studies to correctly establish these comparisons.


Assuntos
Cirurgia Bariátrica/métodos , Obesidade Mórbida/cirurgia , Adulto , Cirurgia Bariátrica/efeitos adversos , Feminino , Humanos , Masculino , Estudos Retrospectivos
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