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INTRODUCTION: Pharmaceutical prescription in systemic sclerosis is guided by national and international recommendations. This study's primary objective was to describe and analyze these prescriptions among patients of our cohort. We also aimed to assess drug compliance among our patients. METHODS: This is a monocentric observational study on two cohorts of patients with systemic sclerosis; a primary cohort comprising ambulatory patients, who were prospectively included, with exhaustive prescription's data collection; and a secondary cohort included patients asked to fill in a self-questionnaire on treatment compliance. RESULTS: The main cohort included 157 patients, including 31 cases of diffuse systemic sclerosis. A vasodilator drug for Raynaud's phenomenon was prescribed in 75 patients (47.9%) and a specific treatment for pulmonary arterial hypertension in 10 patients (6.4%). Immuno-modulators/immunosuppressants was prescribed in 62 patients (39.5%), who received prednisone (n=37, 23.6%), mycophenolate mofetil (n=14, 8.9%), hydroxychloroquine (n=12, 7.6%) and colchicine (n=22, 14%). Treatment for "gastro-intestinal tract involvement" was prescribed for 106 patients (67.5%) and treatment of a scleroderma renal crisis with an angiotensin-converting enzyme inhibitor for 6 patients (3.8%). Among the 42 patients in the secondary cohort, 21.4% reported a good compliance, mostly older patients (P=0.045) or those who had not experienced adverse events (P=0.009). CONCLUSION: This study provides original real-life data illustrating the heterogeneity of prescription habits in systemic sclerosis. As previously reported, treatment compliance was insufficient.
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Preparaciones Farmacéuticas , Enfermedad de Raynaud , Esclerodermia Localizada , Esclerodermia Sistémica , Inhibidores de la Enzima Convertidora de Angiotensina , Humanos , Enfermedad de Raynaud/tratamiento farmacológico , Enfermedad de Raynaud/epidemiología , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/epidemiologíaAsunto(s)
Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/etiología , Carcinoma/diagnóstico por imagen , Esclerodermia Sistémica/complicaciones , Anciano , Anticuerpos Antinucleares/sangre , Resultado Fatal , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: The aim of this study was to describe special features of patients with systemic sclerosis (SSc) diagnosed after the age of 70. PATIENTS AND METHODS: This is a retrospective study of patients aged above 70 years at the time of diagnosis of SSc and followed at an internal medicine unit between 2000 and 2015. Co-morbidities and clinical characteristics were analyzed, as well as survival at 1, 2 and 3 years. RESULTS: Of 246 patients, 27 (11%) were included (89% women, 96% Caucasians, age 78.3±4.5 years). Synchronous cancer was noted in 3 patients. SSc was mostly limited cutaneous only (24/27), with telangiectasia (63%), gastroesophageal reflux (59%) and digital ulcers (22%), and was associated with anti-centromere antibody (69%). Interstitial lung disease was not frequent (29%). Pulmonary arterial hypertension (PAH) was suspected at diagnosis of SSc in 14 cases (52%), but only 5 patients had undergone heart catheterization, with severe PAH in 3 cases. Survival at 1 and 3 years was 85.2% and 66.7%, and was worse in the case of suspected PAH, at 78.6% and 57.1% respectively. CONCLUSION: Cases of SSc diagnosed after 70 years are mostly limited cutaneous forms. Suspicion of PAH is frequent, and PAH may be the main initial sign of the disease for patients at this age. There may be association with synchronous cancer. Survival is poor.
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Medicina Interna , Enfermedades de Inicio Tardío/diagnóstico , Esclerodermia Sistémica/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Francia/epidemiología , Reflujo Gastroesofágico/complicaciones , Humanos , Enfermedades de Inicio Tardío/mortalidad , Enfermedades Pulmonares Intersticiales/complicaciones , Masculino , Estudios Retrospectivos , Factores de Riesgo , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/mortalidad , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/mortalidad , Úlcera Cutánea/complicaciones , Telangiectasia/complicacionesRESUMEN
We present optical studies of two different size distributions of silver triangular nanoprisms, one with a dipole resonance at 520 nm and the other with a dipole resonance at 650 nm, placed in different media. Significant wavelength-dependent depolarization of scattered light from the silver nanoprisms suspended in water indicates strong interference of multiple surface plasmon resonant modes in the same particle. We use this depolarization as a probe of light scattering by the nanoprisms in a lipid solution due to the rejection of a polarized background scattering. Also, the silver nanoprisms were embedded in a polyvinyl alcohol polymer matrix and oriented by stretching the polymer/nanoprism nanocomposite films. We observe significantly increased linear dichroism in the region associated with the plasmonic in-plane dipole mode upon stretching. Additionally, there is a weaker linear dichroism in the region associated with out-of-plane modes, which vanish in the extinction spectrum of the stretched nanocomposite film.
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INTRODUCTION: Jaccoud's arthropathy (JA) is a chronic and non-erosive deforming arthropathy, usually affecting the hands. JA pathophysiology is poorly known but involves periarticular structures such as tendons and the joint capsule. JA is associated with various conditions including the connective tissue disease, especially systemic lupus erythematosis. JA has been rarely described and studied in systemic sclerosis. CASE REPORTS: We report the clinical histories of 3 patients with systemic sclerosis (ScS) who developed JA. One patient had a systemic limited disease and the 2 others a cutaneous limited disease ; mean age of the patients was 79.3 years. Systemic sclerosis was diagnosed respectively 19, 1 and 21 years prior to the development of JA. One of the 3 patients had a past clinical history of discoid lupus. For 1 out of the 3 patients, JA appeared whereas the ScS was completely stable. The disease was still active in the 2 remaining patients, with concurrent pulmonary hypertension diagnosis. Deformities increased during years (Z thumbs, ulnar deviation), leading to mild to severe disability. No benefit from either prednisone (n=2) or a combination of prednisone and methotrexate (n=1) was obtained. CONCLUSION: We described 3 cases of Jaccoud's arthropathy among our scleroderma cohort of 296 patients (1%). This arthropathy worsens hand functional disability. Its pathophysiology is unknown and optimal therapeutic approach remains to establish.
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Deformidades Adquiridas de la Mano/diagnóstico , Artropatías/diagnóstico , Esclerodermia Sistémica/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Deformidades Adquiridas de la Mano/diagnóstico por imagen , Deformidades Adquiridas de la Mano/etiología , Humanos , Artropatías/diagnóstico por imagen , Artropatías/etiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico por imagenRESUMEN
Most peripheral pseudoaneurysms are iatrogenic or, less commonly, post-traumatic. Pseudoaneurysms are associated with characteristic findings of a pulsatile palpable mass and an audible to and fro murmur. The diagnosis can be easily confirmed using colour duplex ultrasound. A successful treatment for the coagulation of pseudoaneurysms as an alternative to ultrasound-guided manual compression is described. The method involves ultrasound-guided direct percutaneous injection of a small quantity of thrombin through a fine needle. This technique is simple and effective, resulting in rapid occlusion of the pseudoaneurysm. Two cases are reported.
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Aneurisma Falso/terapia , Arterias Cerebrales , Coagulantes/administración & dosificación , Arteria Radial , Trombina/administración & dosificación , Ultrasonografía Intervencional , Adulto , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/etiología , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/lesiones , Embolización Terapéutica , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Arteria Radial/diagnóstico por imagen , Arteria Radial/lesiones , Ultrasonografía Doppler en ColorRESUMEN
BACKGROUND: Cancer of the ampulla of Vater kills 60% of affected patients. Local spread of the tumour (T stage) is the only reliable prognostic factor. Nevertheless, any cancer stage includes long term survivors and patients dying from the disease. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. AIM: To evaluate if allelic losses (LOH) of chromosomes 17p and 18q may be of prognostic value in multivariate survival analysis. METHODS: We examined 53 ampullary cancers for chromosome 17p and 18q LOH using microsatellite markers and DNA from paraffin embedded tumours. All patients were treated by surgery alone (pancreaticoduodenectomy). Multivariate survival analysis included age, sex, tumour size, macroscopic appearance, grade of differentiation, T stage, lymph node metastasis, and chromosome 17p and 18q status. RESULTS: Chromosome 17p and 18q LOH were detected in 28 (53%) and 18 (34%) cancers, respectively. Multivariate survival analysis indicated chromosome 17p status as an independent prognostic factor together with T stage. The five year survival for chromosome 17p retention and 17p loss was 80% and 7%, respectively. The risk of death from cancer within the five year follow up period for patients with cancers harbouring chromosome 17p LOH was 11 times higher than that of patients with cancers retaining chromosome 17p (p<0.0001), regardless of the tumour stage at diagnosis. CONCLUSIONS: Chromosome 17p status is an independent prognostic factor among ampullary cancers at the same stage. The combined use of T stage and chromosome 17p status may help in deciding whether ampullary cancer patients require additional therapy other than surgery alone.
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Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco/genética , Adulto , Anciano , Cromosomas Humanos Par 17/genética , Femenino , Estudios de Seguimiento , Genes p53/genética , Humanos , Pérdida de Heterocigocidad/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación/genética , Pronóstico , Tasa de SupervivenciaRESUMEN
During our studies of DNA fingerprinting of tumours of the pancreas and papilla (ampulla) of Vater, using arbitrarily primed polymerase chain reaction (AP-PCR), we noticed two bands showing a decreased intensity in six of ten ampullary tumours with respect to matched normal tissues. Those bands were both assigned to chromosome 5. Such a finding was somewhat in contrast with the reportedly low frequency of APC gene mutations in ampullary cancers, located at chromosome 5q21, and suggested that loci different from that of APC might be the target of chromosome 5 allelic losses (LOH) in these tumours. Therefore, we analysed chromosome 5 LOH in a panel of 27 ampullary tumours, including eight adenomas, four early- and 15 advanced-stage cancers, using 16 PCR-amplified CA microsatellite polymorphic markers spanning the entire chromosome. Nineteen cases (70%) showed LOH, and the interstitial deletions found in these tumours described two smallest common deleted regions, in which putative suppressor genes might reside. They were at 5q13.3-q14 and at 5q23-q31 respectively, which correspond to those found in gastric tumours. In addition, the presence of 5q LOH in six of eight adenomas and in three of four early-stage cancers suggests that such phenomena occur at early stages of neoplastic progression of the ampullary epithelium.
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Adenoma/genética , Ampolla Hepatopancreática , Carcinoma/genética , Cromosomas Humanos Par 5 , Neoplasias Duodenales/genética , Neoplasias Gástricas/genética , Poliposis Adenomatosa del Colon/genética , Adulto , Anciano , Alelos , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
Whether duodenal adenocarcinoma should be considered as a gastrointestinal or as a peripancreatic cancer is a matter of debate, as is the opportunity and type of treatment. We investigated 12 such cancers for the genetic anomalies involved in the pathogenesis of gastrointestinal malignancies, including (a) those occurring in common-type cancers - allelic losses at chromosomes 3p, 5q, 17p and 18q, and Ki-ras and p53 alterations; and (b) those characteristic of mutator-phenotype cancers - microsatellite instability and TGF-betaRII gene mutations. We found Ki-ras and p53 mutations in five (42%) and eight cancers (67%), respectively; chromosome 3p, 5q, 17p and 18q allelic losses in two of nine (22%), six of ten (60%), six of nine (67%) and three of ten (30%) informative cancers, respectively. Finally, three cancers (25%) showed widespread microsatellite instability and two of them had a TGF-betaRII gene mutation. Our data suggest that duodenal cancers may arise from either of the two known pathogenetic molecular pathways of gastric and colorectal cancers. The majority of our cases were highly aggressive cancers with frequent chromosomal changes and p53 mutations as observed in the common-type gastrointestinal malignancies, while widespread subtle alterations characteristic of mutator-phenotype cancers occurred in a minority, which also showed a favourable long-term outcome.
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Carcinoma/genética , Deleción Cromosómica , ADN de Neoplasias/genética , Neoplasias Duodenales/genética , Genes p53 , Genes ras , Receptores de Factores de Crecimiento Transformadores beta/genética , Adulto , Cromosomas Humanos Par 17/ultraestructura , Cromosomas Humanos Par 18/ultraestructura , Cromosomas Humanos Par 3/ultraestructura , Cromosomas Humanos Par 5/ultraestructura , Reparación del ADN/genética , Replicación del ADN , ADN de Neoplasias/biosíntesis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Serina-Treonina Quinasas , Receptor Tipo II de Factor de Crecimiento Transformador betaRESUMEN
Molecular techniques have already earned a place in the management of oncologic disorders. The requests of Clinical Oncologists to Pathologists include, besides the diagnosis, any additional information useful for prognosis and therapeutic choices, as well as expertise and technologies to follow-up patients. To fulfill these commitments, pathologists have been resorting to classical morphology, cytochemistry, immunocytochemistry, and have only recently come to include molecular genetic techniques. Most of the molecular methods of practical utility are based on the analysis of DNA. The DNA methodologies of routine applicability mainly include Southern blotting and polymerase chain reaction (PCR). Southern blotting recognizes major DNA rearrangements, whereas PCR-based methods allow to recognize both gross chromosomal modifications and fine gene alterations, including point mutations. PCR techniques may also be used for many purposes using the partially degraded DNA from formalin-fixed paraffin-embedded tissues. Here we will draw a brief overview of the role of molecular genetic techniques in the pathology practice for the diagnosis, prognosis and follow-up of neoplastic diseases, using examples from our experience in hematology and gastroenterology.
RESUMEN
Cancer of the papilla (ampulla) of Vater is an uncommon disease that kills 60% of affected patients. There is general agreement that local spread of the tumor (T stage) is the only significant and independent prognostic factor for this cancer, whereas the predictive value of tumor grade and lymph node metastases is controversial. The genetic anomalies involved in this process have the potential to serve as additional prognostic markers. We explored 25 ampullary cancers for the occurrence of instability at simple repeat DNA sequences (microsatellites) of the type seen in replication error phenotype (RER-positive) cancers. Ten microsatellites from five different chromosomes were amplified by PCR from both normal and cancer tissue DNA of the same patients. A tumor was defined as RER-positive when microsatellite instability was found in the majority (>/=6) of the loci analyzed. Five cancers (20%) showed a RER phenotype and were associated with long survival of patients (32-96 months), whereas RER-negative cancers had a significantly poorer prognosis (Mantel-Cox test; P = 0.0084), with a median actuarial survival of 17 months. We also report that three (12%) patients belonged to cancer-prone families and four (16%) were cancer-prone individuals.
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Adenoma/genética , Ampolla Hepatopancreática , Carcinoma/genética , Neoplasias del Conducto Colédoco/genética , ADN de Neoplasias/genética , Análisis Actuarial , Adenoma/mortalidad , Adenoma/patología , Adulto , Anciano , Carcinoma/mortalidad , Carcinoma/patología , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Genes p53 , Predisposición Genética a la Enfermedad , Humanos , Metástasis Linfática , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/mortalidad , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/patología , Fenotipo , Reacción en Cadena de la Polimerasa , Pronóstico , Análisis de SupervivenciaRESUMEN
Molecular techniques have already earned a place in the management of hematologic disorders. The requests of clinical hematologists to Pathology include, besides the diagnosis, any additional information useful for prognosis and therapeutic choices, as well as expertise and technologies to follow-up patients. To fulfill these commitments, pathologists have been resorting to classical morphology, cytochemistry, immunocytochemistry, and have only recently come to include molecular genetic techniques. Most of the molecular methods of practical utility are based on the analysis of DNA. The DNA methodologies of routine applicability mainly include Southern blotting and polymerase chain reaction (PCR). Southern blotting recognizes major DNA rearrangements, whereas PCR-based methods allow to recognize both gross chromosomal modifications and fine gene alterations, including point mutations. PCR techniques may also be used for partially degraded DNA from formalin-fixed paraffin-embedded tissues. Here we will draw a brief overview of the role of molecular genetic techniques in the pathology practice for the diagnosis, prognosis and follow-up of neoplastic diseases, using examples from our experience.
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Neoplasias Hematológicas/patología , Southern Blotting , Estudios de Seguimiento , Reordenamiento Génico/genética , Neoplasias Hematológicas/genética , Humanos , Inmunohistoquímica , Mutación Puntual , Reacción en Cadena de la Polimerasa , Pronóstico , Translocación Genética/genéticaRESUMEN
We explored APC gene mutations and chromosome 5q21 allelic losses (5qLOH) in 18 neoplasms of the papilla of Vater, including 6 early-stage tumours (3 adenomas, 3 carcinomas) and 12 advanced-stage cancers. Eleven PCR-amplified polymorphic sequences were used to analyse 5qLOH. APC mutations were investigated both by an in vitro APC-protein truncation test and by single-strand conformation polymorphism analysis. Mutations in the Ki-ras, N-ras and p53 genes were also assessed. We found: 5qLOH in 8 of 16 cases (50%), including 1 adenoma, 3 early- and 4 advanced-stage cancers; APC mutations in 2 adenomas and 1 advanced-stage carcinoma; Ki- or N-ras mutations in 3 adenomas and 3 advanced-stage cancers; p53 mutations in 2 early-stage and 7 advanced-stage adenocarcinomas. Our results suggest that 5qLOH, APC mutations and ras mutations are present at early stages, whereas p53 inactivation is associated with progression of malignancy in a large proportion of cases. These data indicate that sporadic ampullary tumours differ from those occurring in familial adenomatous polyposis in the frequency (17% vs. 64%) as well as in the site of APC somatic mutations, suggesting a different molecular pathogenesis in the 2 conditions.
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Poliposis Adenomatosa del Colon/genética , Alelos , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco/genética , Eliminación de Gen , Genes APC , Mutación , Poliposis Adenomatosa del Colon/complicaciones , Adulto , Anciano , Cromosomas Humanos Par 5 , Neoplasias del Conducto Colédoco/complicaciones , Femenino , Regulación Neoplásica de la Expresión Génica , Genes p53 , Genes ras , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
During our DNA fingerprinting studies of paired normal and pancreatic cancer tissues using arbitrarily primed PCR, we noticed a band showing an apparent homozygous deletion in a pancreatic cancer cell line and a decreased intensity in a number of primary cancers. That band was assigned to chromosome 7. Such information led us to analyze chromosome 7 loss of heterozygosity (LOH) in a panel of 12 cryostat-enriched primary pancreatic cancers and 2 pancreatic cancer cell lines, despite the reportedly low frequency of chromosome 7 LOH in xenograft-enriched pancreatic cancers. Seventeen PCR-amplified CA-microsatellite polymorphic sites were analyzed. One of the two cell lines and eight common-type cancers (including all five poorly differentiated and three of five moderately differentiated cancers) showed chromosome 7q LOH, whereas the two uncommon types of ductal cancer (one adenosquamous and one mucinous noncystic) scored negative. Our data suggest that chromosome 7q LOH is a frequent event (80%) in cryostat-enrichable common pancreatic ductal carcinomas, that is, those primarily of high cellularity. The chromosome 7q smallest common deleted region described by our cases was between 7q31.1 and 7q32.
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Deleción Cromosómica , Cromosomas Humanos Par 7 , Neoplasias Pancreáticas/genética , Adulto , Anciano , Secuencia de Bases , Mapeo Cromosómico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
Se presentan 4 casos de síndrome de shock tóxico asociados a infección por Streptococcus beta-hemolítico grupo A (Streptococcus pyogenes). Todos presentaron hipotensión y disfunción orgánica. Un caso se presentó en forma típica con fascitis necrotizante. Otro paciente tuvo una forma eritrodérmica con posterior descamación asociado a faringitis no invasiva. Una sepsis puerperal con neumonía cavitada y empiema; y un niño con faringitis y bacteremia. Se discute clínica, teorías fisiopatológicas, epidemiología y tratamiento
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Humanos , Masculino , Femenino , Preescolar , Adolescente , Adulto , Persona de Mediana Edad , Infecciones Estreptocócicas/diagnóstico , Streptococcus pyogenes/efectos de los fármacos , Clindamicina/uso terapéutico , Fascitis Necrotizante/diagnóstico , Fascitis Necrotizante/etiología , Infecciones Estreptocócicas/fisiopatología , Infecciones Estreptocócicas/tratamiento farmacológico , Lactamas/uso terapéutico , Miositis/tratamiento farmacológico , Miositis/etiología , Choque Séptico/etiología , Streptococcus pyogenes/patogenicidadRESUMEN
We report a case of a 75-year-old woman admitted to our Unit for chronic sialadenitis, characterized by histologic evidence of B and T lymphocyte infiltrate; laboratory and histologic tests revealed chronic hepatitis C, without autoimmune markers. We found hepatitis C virus (HCV) RNA in liver, in parotid gland, in saliva and in peripheral blood mononuclear cells, but not in serum. HCV RNA was detected by PCR technique. To our knowledge this is the first case of detection of HCV RNA in parotid gland. This finding raises the question about the relationship between sialadenitis and viral HCV infection.
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ADN Viral/aislamiento & purificación , Hepatitis C/virología , Hepatitis Crónica/virología , Glándula Parótida/virología , Sialadenitis/virología , Anciano , Secuencia de Bases , Enfermedad Crónica , ADN Viral/genética , Femenino , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Viral/genéticaRESUMEN
We evaluated four polymerase chain reaction (PCR) methods for their efficiency in detecting monoclonality in a well-characterized panel of frozen and paraffin-embedded B-cell lymphoid proliferations. These approaches (referred to as FR3, FR3A, FR2, and FR1) are based on amplification of rearranged immunoglobulin heavy chain genes, using primers recognizing framework regions I, II, or III. FR3, FR3A and FR2 approaches reproducibly detected monoclonality in 51%, 72%, and 67% of DNAs from frozen lymphomas, respectively. No false-positives were observed. The combination of FR2 and FR3A methods raised the figure to 85%. Comparable results were obtained using paraffin-embedded lymphomas. Reproducibility of FR1 approach was unsatisfactory. The efficiency of all PCR approaches varied depending on lymphoma type. The highest detection rate was in small/intermediate cell and the lowest in centro-follicular lymphomas. Limiting dilution assays showed that PCR methods were able to detect monoclonal B-cell DNA representing 5% of nonlymphoid and 20% of polyclonal B-cell DNA. A diagnostic protocol may include quick and cost-effective PCR screening, particularly in cases of undetermined small cell lymphoid proliferations observed in fine needle aspirates or endoscopic biopsies. This would also reduce call-up of patients to obtain unfixed biopsies.