ABSTRACT
BACKGROUND & AIMS: Topical steroids, proton pump inhibitors (PPIs), and dietary interventions are recommended first- and second-line therapies for eosinophilic esophagitis (EoE). We investigated differences in their effectiveness in a real-world, clinical practice cohort of patients with EoE. METHODS: We collected data on the efficacy of different therapies for EoE (ability to induce clinical and histologic remission) from the multicenter EoE CONNECT database-a database of patients with a confirmed diagnosis of EoE in Europe that began in 2016. We obtained data from 589 patients, treated at 11 centers, on sex, age, time of diagnosis, starting date of any therapy, response to therapy, treatment end dates, alternative treatments, and findings from endoscopy. The baseline endoscopy was used for diagnosis of EoE; second endoscopy was performed to evaluate response to first-line therapies. After changes in treatment, generally because lack of efficacy, a last endoscopy was performed. The time elapsed between endoscopies depended on the criteria of attending physicians. Clinical remission was defined by a decrease of more than 50% in Dysphagia Symptom Score; improvement in symptoms by less than 50% from baseline was considered as clinical response. Histologic remission was defined as a peak eosinophil count below 5 eosinophils/hpf. A peak eosinophil count between 5 and 14 eosinophils/hpf was considered histologic response. We identified factors associated with therapy selection and effectiveness using χ2 and multinomial logistic regression analyses RESULTS: PPIs were the first-line treatment for 76.4% of patients, followed by topical steroids (for 10.5%) and elimination diets (for 7.8%). Topical steroids were most effective in inducing clinical and histologic remission or response (in 67.7% of patients), followed by empiric elimination diets (in 52.0%), and PPIs (in 50.2%). Among the 344 patients who switched to a second-line therapy, dietary interventions were selected for 47.1% of patients, followed by PPIs (for 29.1%) and topical steroids (for 18.6%). Clinical and histologic remission or response was achieved by 80.7% of patients treated with topical steroids, 69.2% of patients given PPIs, and 41.7% of patients on empiric elimination diets. Multivariate analyses found the stricturing phenotype of EoE to be associated with selection of topical steroids over PPIs as the first-line therapy; lack of fibrotic features at initial endoscopy was associated with selection of elimination diets over topical steroids as a second-line therapy. The recruiting center was significantly associated with therapy choice; second-line treatment with topical steroids or PPIs were the only variables associated with clinical and histologic remission. CONCLUSIONS: In an analysis of data from a large cohort of patients with EoE in Europe, we found topical steroids to be the most effective at inducing clinical and histologic remission, but PPIs to be the most frequently prescribed. Treatment approaches vary with institution and presence of fibrosis or strictures.
Subject(s)
Deglutition Disorders , Eosinophilic Esophagitis , Eosinophilic Esophagitis/drug therapy , Eosinophils , Humans , Proton Pump Inhibitors/therapeutic use , Steroids , Treatment OutcomeABSTRACT
Background: Approximately one third of the patients with differentiated thyroid cancer (DTC) who develop structurally-evident metastatic disease are refractory to radioactive iodine (RAI). Most deaths from thyroid cancer occur in these patients. The main objective of this consensus is to address the most controversial aspects of management of these patients. Methods: On behalf of the Spanish Society of Endocrinology & Nutrition (SEEN) and the Spanish Group for Orphan and Infrequent Tumors (GETHI), the Spanish Task Force for Thyroid Cancer, consisting of endocrinologists and oncologists, reviewed the relevant literature and prepared a series of clinically relevant questions related to management of advanced RAI-refractory DTC. Results: Ten clinically relevant questions were identified by the task force. In answering to these 10 questions, the task force included recommendations regarding the best definition of refractoriness; the best therapeutic options including watchful waiting, local therapies, and systemic therapy (e.g. kinase inhibitors), when sodium iodide symporter (NIS) restoration may be expected; and how recent advances in molecular biology have increased our understanding of the disease. Conclusions: In response to our appointment as a task force by the SEEN and GHETI, we developed a consensus to help in clinical management of patients with advanced RAI-refractory DTC. We think that this consensus will provide helpful and current recommendations that will help patients with this disorder to get optimal medical care (AU)
Antecedentes: Alrededor de un tercio de los pacientes con cáncer diferenciado de tiroides (CDT) que desarrollan enfermedad metastásica estructural son refractarios al yodo radiactivo. Desafortunadamente, la mayoría de las muertes debidas al cáncer de tiroides ocurren en pacientes con CDT avanzado refractario al yodo radiactivo. El principal objetivo de este consenso es abordar los aspectos más controvertidos del manejo de estos pacientes. Métodos: En nombre de la Sociedad Española de Endocrinología y Nutrición (SEEN) y del Grupo Español de Tumores Raros e Infrecuentes (GETHI), el grupo de trabajo para el Cáncer de Tiroides, compuesto por endocrinólogos y oncólogos, revisó la literatura más destacada y desarrolló una serie de preguntas clínicamente relevantes concernientes al manejo de los pacientes con CDT refractario. Resultados: Diez preguntas clínicamente relevantes fueron identificadas por el grupo de trabajo. En las respuestas el grupo incluyó recomendaciones sobre la mejor definición de la refractariedad, las mejores opciones terapéuticas, entre las cuales se incluyen la actitud expectante, las terapias locales y la terapia sistémica (por ejemplo inhibidores de tirosín-cinasa), cuándo esperar la recaptación de yodo radiactivo mediada por NIS y cómo los recientes avances en genética molecular han ayudado a comprender mejor la enfermedad. Conclusión: En respuesta a nuestro compromiso como grupo de trabajo de la SEEN y GETHI hemos creado un consenso para asistir al manejo clínico de los pacientes con CDT avanzado refractario al yodo radiactivo. Pensamos que este consenso proporcionará unas recomendaciones útiles y actualizadas que ayuden a los pacientes con esta enfermedad a tener un cuidado óptimo (AU)
Subject(s)
Humans , Thyroid Neoplasms/therapy , Iodine Radioisotopes , Thyroid NeoplasmsABSTRACT
BACKGROUND: Approximately one third of the patients with differentiated thyroid cancer (DTC) who develop structurally-evident metastatic disease are refractory to radioactive iodine (RAI). Most deaths from thyroid cancer occur in these patients. The main objective of this consensus is to address the most controversial aspects of management of these patients. METHODS: On behalf of the Spanish Society of Endocrinology & Nutrition (SEEN) and the Spanish Group for Orphan and Infrequent Tumors (GETHI), the Spanish Task Force for Thyroid Cancer, consisting of endocrinologists and oncologists, reviewed the relevant literature and prepared a series of clinically relevant questions related to management of advanced RAI-refractory DTC. RESULTS: Ten clinically relevant questions were identified by the task force. In answering to these 10 questions, the task force included recommendations regarding the best definition of refractoriness; the best therapeutic options including watchful waiting, local therapies, and systemic therapy (e.g. kinase inhibitors), when sodium iodide symporter (NIS) restoration may be expected; and how recent advances in molecular biology have increased our understanding of the disease. CONCLUSIONS: In response to our appointment as a task force by the SEEN and GHETI, we developed a consensus to help in clinical management of patients with advanced RAI-refractory DTC. We think that this consensus will provide helpful and current recommendations that will help patients with this disorder to get optimal medical care.
Subject(s)
Iodine Radioisotopes/therapeutic use , Iodine/therapeutic use , Thyroid Neoplasms/drug therapy , Consensus , HumansABSTRACT
BACKGROUND: In Spain medullary thyroid carcinoma (MTC) would not exceed 80 new cases per year and less than half of them would be good candidates for systemic treatment with novel agents. METHODS: Relevant literature was reviewed, including PubMed searches supplemented with additional articles. RESULTS: The consensus summarizes the clinical outcomes in terms of activity and toxicity of each of the available drugs. A brief summary of the minimum requirements in terms of follow up and genetic counselling around MTC is also included. CONCLUSIONS: Only those patients with objective imaging progression in the last 12-14 months with large volume of disease are clear candidates to start systemic treatment. However, those patients with low disease volume should be considered for 'wait and see' strategy until symptoms of the disease appear. Multidisciplinary approach for the management of MTC patient is mandatory nowadays
CONTEXTO: Se calcula que la incidencia de cáncer medular de tiroides (MTC) en España no supera los 80 nuevos casos por año y menos de la mitad podrán ser buenos candidatos para recibir tratamiento sistémico con nuevas terapias. Métodos: Se ha revisado la información científica pertinente a través de búsquedas en PubMed y otras fuentes adicionales. Resultados: Este consenso compendia los resultados clínicos en términos de actividad y toxicidad de los fármacos actualmente disponibles. También se aborda un breve resumen con los requerimientos mínimos para el seguimiento y el consejo genético en el CMT. Conclusiones: Los pacientes candidatos para iniciar tratamientos sistémicos son únicamente aquellos con gran carga tumoral en los que se objetiva, mediante pruebas de imagen, una progresión en los últimos 12-14 meses. En aquellos pacientes con escasa carga de enfermedad se debe considerar la observación hasta que aparezcan síntomas de enfermedad. Hoy en día es preceptivo manejar al paciente con MTC por un equipo multidisciplinar
Subject(s)
Humans , Carcinoma, Medullary/diagnosis , Carcinoma, Medullary/therapy , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/therapy , Practice Patterns, Physicians' , Patient Selection , Tumor Burden , Biomarkers, Tumor/analysis , Calcitonin/analysis , Carcinoembryonic Antigen/analysisABSTRACT
BACKGROUND: In Spain medullary thyroid carcinoma (MTC) would not exceed 80 new cases per year and less than half of them would be good candidates for systemic treatment with novel agents. METHODS: Relevant literature was reviewed, including PubMed searches supplemented with additional articles. RESULTS: The consensus summarizes the clinical outcomes in terms of activity and toxicity of each of the available drugs. A brief summary of the minimum requirements in terms of follow up and genetic counseling around MTC is also included. CONCLUSIONS: Only those patients with objective imaging progression in the last 12-14 months with large volume of disease are clear candidates to start systemic treatment. However, those patients with low disease volume should be considered for 'wait and see' strategy until symptoms of the disease appear. Multidisciplinary approach for the management of MTC patient is mandatory nowadays.
Subject(s)
Carcinoma, Medullary/therapy , Thyroid Neoplasms/therapy , Anilides/therapeutic use , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor , Calcitonin/blood , Carcinoembryonic Antigen/analysis , Carcinoma, Medullary/epidemiology , Carcinoma, Medullary/genetics , Combined Modality Therapy , Diagnostic Imaging/methods , Disease Management , Doxorubicin/therapeutic use , Genetic Association Studies , Humans , Neoplasm Metastasis , Prognosis , Proto-Oncogene Proteins c-ret/genetics , Pyridines/therapeutic use , Radiotherapy/methods , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/geneticsABSTRACT
Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is a rare but highly lethal form of thyroid cancer that requires a multidisciplinary team approach. No Spanish consensus exists for management of patients with ATC. The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology, in agreement with the Boards of these Societies, commissioned an independent task force to develop a wide consensus on ATC. The relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The consensus includes the characteristics, diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active treatment), approaches to advanced/metastatic disease, palliative care options, monitoring, and long-term follow-up of ATC. For operable disease, a combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy. Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other hand, targeted agents may represent a viable therapeutic option. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for clinical trials or or for hospice/palliative care depending on their preference. This is the first Spanish consensus for ATC, and provides recommendations for management of this extremely aggressive malignancy. Novel systemic therapies are being tested, and more effective combinations are needed to improve patient outcomes. Although more aggressive radiotherapy has reduced locoregional recurrence, mean overall survival has not improved in the past 50 years
El cáncer anaplásico de tiroides (CAT) es el tumour sólido más agresivo conocido y es una forma rara pero muy letal de cáncer de tiroides que requiere un enfoque multidisciplinario. No existe ningún consenso español para definir la conducta a seguir en los pacientes con CAT. El Grupo de Cáncer de Tiroides de la Sociedad Española de Endocrinología y Nutrición y el GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) de la Sociedad Española de Oncología, de acuerdo con las Juntas Directivas de estas Sociedades decidieron que un grupo de trabajo independiente desarrollaran un amplio consenso sobre el CAT. Se revisó la literatura relevante, incluyendo la búsqueda en PubMed de las series más relevantes. En el consenso se incluyen las características, el diagnóstico, la evaluación inicial, el establecimiento de los objetivos del tratamiento, la actitud a seguir ante la enfermedad locorregional (cirugía, radioterapia, terapia sistémica, la atención de apoyo durante el tratamiento activo), acerca a la enfermedad avanzada/metastásica, las opciones de cuidados paliativos, la vigilancia y el seguimiento a largo plazo del CAT. Para la enfermedad operable, la combinación de la cirugía radical con radioterapia o quimioterapia adyuvante, utilizando agentes tales como doxorrubicina, cisplatino y paclitaxel, es la mejor estrategia de tratamiento. Los fármacos citotóxicos para los casos avanzados/metastásicos de CAT son poco eficaces. Por otra parte, los agentes dirigidos a dianas específicas pueden representar una opción terapéutica viable. Los pacientes con enfermedad resecable en estadio IVA/IVB tienen el mejor pronóstico, sobre todo si se utiliza un enfoque multimodal, y algunos pacientes no resecables etapa IVB pueden responder a una terapia agresiva. En los pacientes con enfermedad en estadio IVC se debe considerar o bien si son aptos para entrar en un ensayo clínico o bien para cuidados paliativos, dependiendo de la preferencia del paciente. Este es el primer consenso español para el CAT y ofrece recomendaciones para la conducta a seguir en este tumour maligno extremadamente agresivo. Las terapias sistémicas más recientes están siendo evaluadas, y se necesitan combinaciones más eficaces para mejorar los resultados en los pacientes tratados. Aunque la radioterapia más agresiva ha reducido las recurrencias locorregionales, la media de supervivencia global no ha mejorado en los últimos 50 años
Subject(s)
Humans , Thyroid Neoplasms/therapy , Anaplasia/therapy , Lymphatic Metastasis , Genetic Predisposition to Disease , Biopsy/methods , Thyroidectomy/methodsABSTRACT
Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is a rare but highly lethal form of thyroid cancer that requires a multidisciplinary team approach. No Spanish consensus exists for management of patients with ATC. The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology, in agreement with the Boards of these Societies, commissioned an independent task force to develop a wide consensus on ATC. The relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The consensus includes the characteristics, diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active treatment), approaches to advanced/metastatic disease, palliative care options, monitoring, and long-term follow-up of ATC. For operable disease, a combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy. Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other hand, targeted agents may represent a viable therapeutic option. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for clinical trials or for hospice/palliative care depending on their preference. This is the first Spanish consensus for ATC, and provides recommendations for management of this extremely aggressive malignancy. Novel systemic therapies are being tested, and more effective combinations are needed to improve patient outcomes. Although more aggressive radiotherapy has reduced locoregional recurrence, mean overall survival has not improved in the past 50 years.
Subject(s)
Thyroid Carcinoma, Anaplastic/therapy , Thyroid Neoplasms/therapy , Algorithms , Humans , SpainABSTRACT
It has been reported that large genomic deletions in the MLH1 and MSH2 genes are a frequent cause of Lynch syndrome in certain populations. Here, a cohort has been screened and two new founder rearrangements have been found in the MSH2 gene. These mutations have been characterized by break point determination, haplotype analysis, and genotype-phenotype correlation. Mutations have been identified in the MLH1, MSH2, and MSH6 genes in 303 subjects from 160 suspected Lynch syndrome unrelated families. All subjects were tested using heteroduplex analysis by capillary array electrophoresis. Multiplex ligation-dependent probe amplification was used to detect rearrangements in mutation-negative index patients and confirmed by reverse transcriptase PCR. The break point of the deletions was further characterized by the array comparative genomic hybridization method. Immunohistochemical staining and microsatellite instability were studied in tumor samples. Hereditary nonpolyposis colorectal cancer-related phenotypes were evaluated. More than 16% (24 of 160) of the families had pathogenic mutations (8 MLH1, 15 MSH2, and 1 MSH6). Twelve of these families (50%) are carriers of a novel mutation. Seven of the 15 positive MSH2 families (47%) are carriers of a rearrangement. The exon 7 deletion and exon 4 to 8 deletion of MSH2 are new founder mutations. The segregation of a common haplotype, a similar phenotype, and anticipation effects were observed in these families. These findings will greatly simplify the diagnosis, counseling, and clinical care in suspected Lynch syndrome families and not just in specific geographic areas, so wide distribution may be explained by migration patterns.
Subject(s)
Alu Elements/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Gene Rearrangement , Germ-Line Mutation/genetics , MutS Homolog 2 Protein/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , Case-Control Studies , Cohort Studies , Comparative Genomic Hybridization , DNA/genetics , DNA Mutational Analysis , Exons/genetics , Female , Founder Effect , Genetic Association Studies , Haplotypes , Humans , Immunoenzyme Techniques , Male , Microsatellite Instability , Middle Aged , Molecular Sequence Data , MutS Homolog 2 Protein/metabolism , Pedigree , Phenotype , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Deletion , Sequence Homology, Nucleic Acid , Young AdultSubject(s)
Adenomatous Polyposis Coli , Colorectal Neoplasms, Hereditary Nonpolyposis , Adenomatous Polyposis Coli/diagnosis , Adenomatous Polyposis Coli/epidemiology , Adenomatous Polyposis Coli/genetics , Adenomatous Polyposis Coli/surgery , Adult , Colectomy , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/surgery , Genetic Counseling , Genetic Predisposition to Disease , Genotype , Humans , Incidence , Mutation , Phenotype , Proctocolectomy, Restorative , Risk Factors , Spain/epidemiologyABSTRACT
No disponible
Subject(s)
Humans , Colonic Neoplasms/genetics , Genetic Diseases, Inborn/genetics , Immunohistochemistry , Colonic Neoplasms/diagnosisABSTRACT
BACKGROUND: Baker's asthma is a frequent occupational allergic disorder mainly caused by inhalation of cereal flours. Lipid transfer proteins (LTPs) constitute a family of plant food panallergens, but their role as inhalant and wheat allergens is still unclear. OBJECTIVE: We sought to explore the involvement of wheat LTPs in baker's asthma caused by wheat flour sensitization. METHODS: Forty patients with occupational asthma caused by wheat flour inhalation were studied. Wheat LTP, Tri a 14, was purified by using a 2-step chromatographic protocol and characterized by N-terminal amino acid sequencing and 3-dimensional modeling. Its reactivity was confirmed by means of IgE immunodetection, ELISA and ELISA-inhibition assays, and skin prick tests. RESULTS: Specific IgE to Tri a 14 was found in 60% of 40 individual sera from patients with baker's asthma, and the purified allergen elicited positive skin prick test reactions in 62% of 24 of these patients. Tri a 14 and peach LTP, Pru p 3, showed a sequence identity of 45%, but the low cross-reactivity between both allergens detected in several individual sera reflected great differences in their 3-dimensional IgE-binding regions. CONCLUSIONS: Wheat LTP is a major inhalant allergen associated with baker's asthma caused by wheat flour sensitization. Poor cross-reactivity with its peach homolog was found in some patients. CLINICAL IMPLICATIONS: LTPs can be considered relevant inhalant allergens linked to respiratory disorders. LTP from wheat (Tri a 14) can be used as a helpful tool for the diagnosis of baker's asthma.
Subject(s)
Antigens, Plant/immunology , Asthma/immunology , Carrier Proteins/immunology , Inhalation Exposure , Occupational Diseases/immunology , Triticum/immunology , Adult , Antigens, Plant/analysis , Carrier Proteins/analysis , Epitopes/chemistry , Epitopes/immunology , Female , Flour , Humans , Immunoglobulin E/blood , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Protein Conformation , Triticum/chemistryABSTRACT
BACKGROUND: Skin testing and sera measurements have verified the existence of tobacco specific IgE. However, the few published studies on this matter report conflicting results concerning their clinical significance. OBJECTIVE: To verify if a specific clinical allergenic response against tobacco might be possible in allergenic and nonallergenic bronchial diseases. METHODS: We performed a cross-sectional observational case-control analysis on 180 patients with asthma, chronic obstructive pulmonary disease (COPD), and bronchial carcinoma and controls who were randomly chosen. Skin prick tests and serum specific IgE to tobacco and related allergens, bronchial challenge with cigarettes and tobacco extract, patch tests with tobacco and nicotine, sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting, and Enzyme AllergoSorbent Test (EAST) inhibition were performed. RESULTS: Twenty-eight patients had positive tobacco skin prick test results. The association among positive skin prick test results, IgE, and bronchial challenge was strong (P < .001). Tobacco sensitivity was higher in patients with pollen asthma than in patients with COPD and carcinoma and negative in patients with intrinsic asthma and controls. A positive bronchial challenge result was related to the length of habit (P < .001) and the tobacco index in patients who had stopped smoking (P < .001). Delayed bronchial and patch response was more common in patients with COPD (P < .001). Tobacco IgE response (EAST) was related to sensitivity to Lolium perenne (rye grass) pollen (P < .001) but not to other vegetables that belong to the Solanaceae family. EAST inhibition showed cross-reactivity between tobacco and Lolium pollen. CONCLUSIONS: Tobacco may be responsible for a specific IgE response. Patients with pollen asthma were those with more positive responses to tobacco due to cross-reactivity between Lolium and tobacco allergens.
Subject(s)
Allergens , Asthma/immunology , Bronchial Neoplasms/immunology , Nicotiana/immunology , Adolescent , Adult , Asthma/blood , Bronchial Neoplasms/blood , Bronchial Provocation Tests , Case-Control Studies , Cross Reactions , Cross-Sectional Studies , Female , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Male , Middle Aged , Pollen , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/immunology , Skin TestsABSTRACT
People with Type 2 diabetes have bone mass alterations and may have a higher risk of hip fractures. Moreover, they have increased cardiovascular risk factors. The objective of this paper is to investigate the association among non-insulin-dependent diabetes, bone mineral density (BMD), and cardiovascular risk factors. Ninety-two patients (36 males and 56 females) were studied and cardiovascular risk factors were measured: total cholesterol, triglycerides, lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose, HbA1c, and microalbuminuria. The densitometric studies were carried out in the calcaneal region using a DEXA densitometer. The diabetic women had a higher BMD than the control group (0.502 +/- 0.127 vs. 0.408 +/- 0.102, P = .027). The women showed a positive relationship between BMD and triglycerides (r =. 478, P = .0001) and a negative relationship with HDL-C (r = -.322, P = .016). The men had a BMD similar to that of the control group, and there was no relationship with the cardiovascular risk factors. When a multivariate logistic regression analysis was performed with the presence of osteoporosis as a dependent variable and each lipid level, age, sex, and BMI as independent variables, only age and BMI were found to be associated with the presence of osteopososis. The diabetic women had a higher BMD than the controls, and there was no relationship between osteoporosis and cardiovascular risk factors in diabetics.
Subject(s)
Bone Density , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/epidemiology , Aged , Body Mass Index , Cholesterol/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Female , Homocysteine/blood , Humans , Lipoproteins/blood , Male , Middle Aged , Risk Factors , Sex Characteristics , Triglycerides/bloodABSTRACT
BACKGROUND: Members belonging to 9 different families of plant pathogenesis-related (PR) proteins have been identified as pollen and food allergens. However, no PR-1 protein, a family widely distributed throughout the plant kingdom, has been involved so far in allergic reactions. On the other hand, melon ranges among the most relevant fruits causing food allergy in some countries, but the majority of its allergens remain still unidentified. OBJECTIVE: We sought to identify melon allergens related to plant PR proteins. METHODS: A serum pool or individual sera from 17 patients with allergy to melon confirmed by means of double-blind, placebo-controlled food challenge were used to detect IgE binding proteins of extracts from melon pulp and juice. Cuc m 3 was isolated from melon juice by reverse-phase HPLC and characterized by means of N-terminal amino acid sequencing of internal peptides, matrix-assisted laser desorption/ionization mass spectrometry analysis, direct and inhibition ELISA assays, and skin prick tests. RESULTS: Cuc m 3 was a minor component of the melon juice, with a molecular weight of 16,097 d and a blocked N-terminus. N-terminal amino acid sequences of 3 different peptides derived from endo-Lys C digestion (overall 41 residues) showed more than 60% of sequence identity with PR-1 proteins from grape and cucumber. Cuc m 3 bound IgE from 12 of 17 sera from patients allergic to melon and inhibited approximately 40% and 70% of the IgE binding to melon pulp and juice extracts, respectively. Positive skin prick test responses to purified Cuc m 3 were found in 2 of 14 allergic patients. CONCLUSION: A new melon allergen belonging to the PR-1 protein family has been isolated and characterized. It is the first evidence of the involvement of this plant protein family in food allergy.
