ABSTRACT
Inherited bleeding coagulation disorders (IBCDs) have a powerful diagnostic tool in next generation sequencing (NGS) that not only offers confirmation of diagnosis but also aids in genetic counselling, prenatal diagnosis and helps to predict the clinical course and follow-up of a disease. In our group, targeted-NGS using a Custom SureSelect QXT Panel (Agilent Technologies, Inc., Santa Clara, CA, USA) was designed to screen for causal variants in 40 genes related with the coagulation cascade. In this work, we used NGS for screening all the coding and intronic boundary regions of F5 gene in two patients affected by factor V (FV) deficiency (parahemophilia). Two new mutations were found: c.4745A>G (p.Tyr1582Cys, NM_000130.4) and c.1999_2002dupAATT (p.Ser668ter; NM_000130.4), both located in exon 13 of the F5 gene. We designated them Valencia-1 and Valencia-2 respectively. Valencia-1 could provoke loss of the fifth cupredoxin domain of the FV, and would be responsible for its defective activity. Valencia-2 prematurely stops the translation of mRNA, resulting in a truncated FV protein which lacks completely the B domain and the light chain. NGS has permitted to describe an increasing number of FV deficiency-causing mutations and a better understanding of FV's structure and function. The description of deficiency-causing mutations will continue to increase our knowledge of the functional residues of FV, as well as those which are involved in the correct folding of the protein. In this sense, NGS is a useful tool for studying IBCDs, as permits studying the whole coagulation cascade at once and gives a global view of the patient's genetic background.
Subject(s)
Factor V Deficiency/genetics , Factor V/genetics , High-Throughput Nucleotide Sequencing , Blood Coagulation Disorders, Inherited/genetics , Codon, Nonsense , Genetic Variation , Humans , Mutation , Point MutationABSTRACT
Erythema annulare centrifugum (EAC) is a clinical reaction pattern that includes lupus erythematosus, spongiotic dermatitis (particularly pityriasis rosea), pseudolymphoma and cutaneous B-cell lymphoma. However, it can be the result of cutaneous metastasis by an internal carcinoma. We present the case of a 38-year-old woman with bilateral inflammatory breast cancer following multimodal therapy. After chemotherapy, the patient developed EAC on her back, clinically suspect of subacute cutaneous lupus erythematosus. A skin biopsy of annular lesion revealed dermal lymphatic infiltration by inflammatory breast carcinoma. Immunohistochemically, HER2 overexpression and negativity for hormone receptor are the hallmarks of this disease. Cutaneous metastasis by inflammatory breast carcinoma mimicking EAC is rare, and it has not been described in extramammary locations. Its recognition by the dermatologist is important because it can be a clinical manifestation of locally recurrent cancer.
Subject(s)
Carcinoma/secondary , Erythema/pathology , Inflammatory Breast Neoplasms/pathology , Skin Diseases, Genetic/pathology , Skin Neoplasms/secondary , Adult , Diagnosis, Differential , Female , HumansSubject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma/genetics , Multiple Myeloma/therapy , Neoplasm, Residual , Transplantation Conditioning/methods , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Humans , Prospective Studies , Real-Time Polymerase Chain Reaction , Recurrence , Transplantation, HomologousABSTRACT
Here we report the clinical, pathological, and immunological features of a rare case of Waldenström macroglobulinemia (WM) with pleural infiltrations. An atypical chylothorax, successfully treated by videothoracoscopy, represented the main clinical feature of this case of low-grade lymphoplasmacytic lymphoma. Pleuropulmonary manifestations are rare (from 0 to 5% of cases) in WM, with chylothorax observed in just seven patients worldwide. In addition to describing this uncommon clinical presentation, we investigate hypothetical pathogenetic mechanisms causing chylothorax and through an up-todate review of available literature furnish helpful suggestions for diagnosis and management of chylothorax in WM patients.
Subject(s)
Chylothorax/etiology , Pleural Neoplasms/complications , Waldenstrom Macroglobulinemia/complications , Aged , Chylothorax/diagnostic imaging , Chylothorax/immunology , Chylothorax/therapy , Humans , Male , Pleural Neoplasms/diagnostic imaging , Pleural Neoplasms/immunology , Pleurodesis/methods , Talc/therapeutic use , Thoracic Surgery, Video-Assisted/methods , Tomography, X-Ray Computed , Waldenstrom Macroglobulinemia/diagnostic imaging , Waldenstrom Macroglobulinemia/immunologyABSTRACT
Immunophenotypic remission (IR) is a strong prognostic factor in myeloma patients. The combination of IR and conventional CR was retrospectively evaluated in 66 patients after allografting. IR was defined as the absence of monoclonal plasma cells in BM aspirates by multiparameter flow cytometry. Conditioning was non-myeloablative in 55 patients; reduced-intensity in 10 and myeloablative in 1 patient. The allograft was given upfront in 35/66 (53%) patients. After a median follow-up of 7.1 years, 24 patients achieved both CR and IR (CR/IR group), 21 achieved IR but not CR with persistence of a urine/serum M-component (no CR/IR group) and 21 did not achieve either CR or IR (no CR/no IR group). Median OS and EFS were 'not reached' and 59 months in the CR/IR group; 64 and 16 months in the no CR/IR; and 36 and 6 months in the no CR/no IR, respectively (P<0.001). Cumulative incidence of extramedullary disease was 4.4% in the CR/IR, 38.1% in the no CR/IR and 14.3% in the no CR/no IR groups, respectively, at 4 years (P<0.001). IR was a valid tool to monitor residual disease after allografting, and allowed definition of a cohort of patients at higher incidence of extramedullary relapse.
Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma/mortality , Multiple Myeloma/therapy , Adult , Aged , Allografts , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Remission Induction , Survival RateABSTRACT
We present a case of Trichoderma fungemia with pulmonary involvement in a multiple myeloma patient, who was severely immunocompromised and heavily treated with high-dose melphalan, and underwent autologous hematopoietic cell transplantation. This is the first report, to our knowledge, of proven Trichoderma fungemia, defined by published criteria, successfully treated with voriconazole.
Subject(s)
Antineoplastic Agents/adverse effects , Fungemia/microbiology , Mycoses/microbiology , Stem Cell Transplantation/adverse effects , Trichoderma/isolation & purification , Antifungal Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Humans , Male , Middle Aged , Mycoses/drug therapy , Trichoderma/classification , Voriconazole/therapeutic useABSTRACT
El queratoacantoma es un tumos de rápido crecimiento que recuerda históricamente al carcinoma de células escamosas. El tratamiento (..) (AU)
Keratoacanthoma is a rapidly growing tumour that histologically resembles squamous cell carcinoma. Most (..) (AU)
Subject(s)
Humans , Female , Middle Aged , Keratoacanthoma/drug therapy , Immunologic Factors/pharmacokinetics , Eyelid Neoplasms/drug therapy , Administration, Topical , Eye Neoplasms/drug therapySubject(s)
Prostatic Neoplasms/pathology , Solitary Fibrous Tumors/pathology , 12E7 Antigen , Adenocarcinoma/diagnosis , Aged , Antigens, CD/analysis , Antigens, CD34/analysis , Biomarkers, Tumor/analysis , Cell Adhesion Molecules/analysis , Diagnosis, Differential , Humans , Male , Neoplasm Proteins/analysis , Prostate-Specific Antigen/analysis , Prostatectomy/methods , Prostatic Neoplasms/blood , Prostatic Neoplasms/chemistry , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/surgery , Proto-Oncogene Proteins c-bcl-2/analysis , Solitary Fibrous Tumors/blood , Solitary Fibrous Tumors/chemistry , Solitary Fibrous Tumors/diagnosis , Solitary Fibrous Tumors/surgeryABSTRACT
SUMMARY BACKGROUND: There is currently intense debate as to whether pharmacogenetic algorithms for estimating the initial dose of coumarins provide a more accurate dose than the fixed-dose approach. Recently, it has been suggested that the greatest benefit of pharmacogenetic algorithms is observed in patients with extreme dose requirements. OBJECTIVES: To identify clinical and genetic factors that better characterize patients who need extreme acenocoumarol doses for steady anticoagulation state. PATIENTS/METHODS: We reviewed 9538 patients with a steady acenocoumarol dose from three Spanish hospitals, selecting 83 who took
Subject(s)
Acenocoumarol/pharmacology , Anticoagulants/pharmacology , Pharmacogenetics , Acenocoumarol/administration & dosage , Adult , Aged , Anticoagulants/administration & dosage , Aryl Hydrocarbon Hydroxylases/genetics , Base Sequence , Cytochrome P-450 CYP2C9 , Cytochrome P-450 Enzyme System/genetics , Cytochrome P450 Family 4 , DNA Primers , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Mixed Function Oxygenases/genetics , Polymorphism, Single Nucleotide , Vitamin K Epoxide ReductasesABSTRACT
No disponible
Subject(s)
Humans , Male , Middle Aged , Prostatic Neoplasms/complications , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/surgery , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/surgery , Prostatectomy/methods , Prostatectomy/trends , Transurethral Resection of Prostate/methods , Prostatic Neoplasms/pathology , Prostatic Neoplasms , Ureteral Obstruction/complications , Urethral Obstruction/complications , Immunohistochemistry/methodsABSTRACT
Summary Mid-dermal elastolysis is an unusual process characterized by the absence of the elastic fibres within the mid-dermis. The disappearance of these fibres causes fine wrinkles (type 1) or perifollicular protrusions (type 2) affecting the trunk, neck and arms. There is a female predilection, and most patients have a history of intense sun exposure. Recently, some cases of mid-dermal elastolysis presenting as reticular erythema have been reported. We report a case of reticular erythema with mid-dermal elastolysis that occurred in a 70-year-old man after insertion of a pacemaker.
Subject(s)
Cutis Laxa/pathology , Erythema/pathology , Pacemaker, Artificial/adverse effects , Aged , Cutis Laxa/etiology , Erythema/etiology , Humans , MaleABSTRACT
No disponible
No disponible
Subject(s)
Male , Middle Aged , Humans , Health Knowledge, Attitudes, Practice , Calciphylaxis/complications , Calciphylaxis/diagnosis , Calciphylaxis/therapy , Anticoagulants/therapeutic use , Calciphylaxis/psychology , Nadroparin/therapeutic use , Thrombophilia/complications , Erythema/complications , Erythema/diagnosis , Hyperparathyroidism/complications , Proteinuria/complicationsABSTRACT
No disponible
Subject(s)
Aged , Male , Humans , Thrombocytopenia/diagnosis , Edetic Acid/analysis , Liver Cirrhosis/complications , Prostatic Neoplasms/complicationsABSTRACT
La determinación de la velocidad de eritrosedimentación (VS) es una de las pruebas más utilizadas en la práctica clínica, útil para indicar la presencia de enfermedad, seguir el curso evolutivo de procesos inflamatorios y comprobar la respuesta a tratamientos. La determinación de la VS conlleva la extracción de un tubo exclusivo de sangre con citrato, seguida de un ensayo de laboratorio que precisa de un tiempo prolongado. Sería deseable la aparición de un nuevo test de medición de la VS que posibilitara la integración de la medida de VS con la hematología automatizada, empleando microvolúmenes de sangre anticoagulada con EDTA, y que permitiera una determinación rápida y de forma continua. El objetivo de este estudio es valorar la aplicabilidad del nuevo analizador Test 1 (Sire Analytical Systems, Udine, Italia), que emplea una tecnología basada en la fotometría capilar cuantitativa, evaluando su reproducibilidad y estabilidad y comparando los resutados obtenidos para la VS con los obtenidos mediante el analizador Ves-MAtic (Diesse, Milán, Italia) y con los valores de las medidas de viscosidad plasmática. Para ello, se determinaron las VS de 375 pacientes, emplando muestras anticoagulantes con K3-EDTA para el Test 1 y con citrato sódico para el Ves-Matic. Además, se ha valorado la viscosidad plasmática en 39 de los 375 pacientes. La reproducibilidad intra-ensayo del Test 1 fue satisfactoria y su estabilidad fue aceptable durante las primeras 24 horas, manteniendo las muestras a 4ºC. Sin embargo, al comparar los valores de VS obtenidos mediante el analizador Test 1 y el sistema Ves-MAtic, mediante el coeficiente de correlación de Pearson y el análisis de Bland-Altman, se llegó a la conclusión de que los dos métodos presentan diferencias significativas, por lo que no son intercambiables. Por otra parte, las medidas de viscosidad plasmática se correlacionan mejor con las determinaciones del VS obtenidad con el Test 1 que con las obtenidas con el Ves-Matic. El Test 1 tiene numerosas ventajas operativas evidentes. Sin embargo, al basarse en principios físicos completamente diferentes a los sistemas habituales de medida de la VS, la variable física que se determina no es completamente equivalente a ésta. Serían necesarios estudios más profundos acerca del significado clínico de las determinaciones realizadas mediante el analizador Test 1, antes de su introducción en el laboratorio clínico como sustituto de los actuales analizadores de VS (AU)
Subject(s)
Humans , Electronic Data Processing , Blood Sedimentation , Reproducibility of Results , Blood ViscosityABSTRACT
Enantiopure forms of alpha,alpha'-bis(trifluoromethyl)-9,10-anthracenedimethanol and the corresponding perdeuterated isotopomers were prepared. The conformational study was carried out by (1)H NMR, and the absolute configuration was determined by the X-ray study of the crystallized diastereoisomeric carbamate derivative. This compound was tested as a chiral solvating agent (CSA). The results showed very good discrimination for several racemic mixtures that improved other classical methods. The study of diastereomeric complexes was carried out by determination of the stoichiometry of the complex and the binding constant of the equilibrium.
ABSTRACT
The aim of this study was to evaluate the potential capacity of color and power Doppler sonography with intravenous contrast medium in the diagnosis of acute cholecystitis. We examined 18 patients with acute cholecystitis, 5 patients with chronic cholecystitis and a control group of 11 patients without gallbladder disease. In these patients, vascularization of the gallbladder wall was evaluated by color and power Doppler sonography before and after intravenous administration of contrast medium (Levograf). Vascularization was evaluated with a 3-point scale (grades 0, 1 and 3) according to the intensity and localization of signs of color. In the diagnosis of acute cholecystitis, basal examination with power Doppler had a sensitivity of 38.8%. After administration of intravenous contrast medium, sensitivity was 100%. In conclusion, the use of sonographic contrast media in the diagnosis of acute cholecystitis showed a sensitivity and specificity of 100%. This technique represents a viable diagnostic alternative to other complementary or imaging studies.
Subject(s)
Cholecystitis/diagnostic imaging , Contrast Media , Ultrasonography, Doppler , Acute Disease , Adult , Contrast Media/administration & dosage , Female , Humans , Injections, Intravenous , Male , Middle Aged , Prospective StudiesABSTRACT
Undesirable temperature gradients in a NMR sample tube are usually generated by an inappropriate temperature regulation system. We have shown that such convection effects can greatly distort the measurement of translational self-diffusion coefficients. The use of sample spinning helps to minimize such undesirable effects by disruption of convection fluxes due to resulting Coriolis forces that have a strongly stabilizing effect on the conducting state of the system (J. Lounila et al., J. Magn. Reson. A 118, 50 (1996)). This simple trick allows the accurate measurement of diffusion coefficients for a wide range of temperatures and solvents without the need for a convection-compensated NMR pulse sequences or more sophisticated temperature control units. Experimental data obtained for some target compounds dissolved in several common deuterated solvents at different temperatures are reported and discussed.
