RESUMEN

BACKGROUND: Nutrition incentive (NI) programs increase the purchase of fruits and vegetables (FVs) among low-income participants. Double Up Food Bucks (DUFB) is a robust statewide NI program in the United States. The purpose of this paper is to report findings from DUFB in Michigan describing the factors related to FV intake (FVI) and food insecurity among participants in a NI program. METHODS: We administered a repeated cross-sectional survey with a convenience sample of DUFB participants at farmers markets and grocery stores (over the 2016, 2017, 2018 seasons). The survey was conducted online via paper-pencil. Descriptive statistics were calculated for all variables. A logistic regression model estimated household food insecurity and a linear regression estimated FVI with DUFB use/perceptions, sociodemographics, and health status as independent variables (significance level = p < 0.05). RESULTS: Descriptive results revealed that participants that completed surveys at grocery stores tended to be more racially-ethnically diverse and younger than participants that completed surveys at farmers markets. Participants with lower length of time participating in DUFB (i.e., lower dose) (p < 0.001), greater FV purchases (p < 0.05), and lower perceived health status (p < 0.001) tended to report being food insecure more frequently. Participants with increased length of time participating in DUFB (p < 0.05), greater FV purchases (p < 0.001), being male (p < 0.01), and greater perceived health status (p < 0.001) tended to report higher levels of FVI more frequently. CONCLUSIONS: Longer participation in DUFB leads to improved outcomes with FVI and food security, suggesting that NI programs do have the intended positive impact they were designed to achieve.

RESUMEN

Our objective was to evaluate the effect of manipulating progesterone (P4) concentrations before timed artificial insemination (TAI) on reproductive and endocrine outcomes in high-producing Holstein cows. Multiparous lactating Holstein cows (n = 80) were synchronized for first TAI using a Double-Ovsynch protocol and were randomly assigned to receive 25 mg of PGF2α 1 d after the first GnRH treatment of the Breeding-Ovsynch protocol that included a once-used P4 insert (low-P4 group) or to receive 2 new P4 inserts during the Breeding-Ovsynch protocol (high-P4 group). Blood samples were collected thrice weekly from -10 to 32 d relative to TAI for all cows and from 32 to 67 d after TAI for pregnant cows and were analyzed for P4 and pregnancy-specific protein B (PSPB) concentrations. Expression of IFNτ-stimulated gene 15 (ISG15) was assessed in blood leukocytes 18 and 20 d after TAI. As expected, P4 concentrations were greater for high-P4 cows than for low-P4 cows from 3 to 8 d before TAI. Incidence of double ovulation was 3-fold greater for low-P4 cows than for high-P4 cows (33 vs. 10%), which resulted in more twin pregnancies 32 d after TAI for low-P4 cows than for high-P4 cows (29 vs. 0%). Low-P4 cows had larger preovulatory follicles at the last GnRH treatment of the Double-Ovsynch protocol and greater P4 concentrations than high-P4 cows after TAI. Relative expression of ISG15 mRNA 18 and 20 d after TAI was greater for low-P4 cows than for high-P4 cows and for pregnant cows than for nonpregnant cows. Overall, PSPB concentrations tended to be greater for low-P4 cows than for high-P4 cows, and pregnant cows had greater P4 concentrations than nonpregnant cows. In summary, cows with low P4 before TAI had increased preovulatory follicle diameter, PSPB concentrations, relative expression of ISG15 mRNA 18 and 20 d after TAI, double ovulations, and twinning compared with cows with high P4 before TAI. Increasing P4 before TAI may effectively decrease double ovulation and twinning in high-producing multiparous Holstein cows.

Asunto(s)

Bovinos/fisiología , Progesterona/administración & dosificación , Animales , Cruzamiento , Dinoprost/administración & dosificación , Sincronización del Estro , Femenino , Hormona Liberadora de Gonadotropina/administración & dosificación , Inseminación Artificial/veterinaria , Lactancia , Masculino , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/fisiología , Ovulación/efectos de los fármacos , Paridad , Embarazo , Progesterona/sangre , Reproducción/efectos de los fármacos

RESUMEN

Our objective was to assess the effect of treatment with human chorionic gonadotropin (hCG) 7 d after artificial insemination (AI) or at the time of in vitro-fertilized (IVF) embryo transfer on reproductive outcomes, including progesterone (P4), interferon-tau stimulated gene 15 (ISG15), pregnancy-specific protein B (PSPB), and pregnancies per AI (P/AI) or pregnancies per embryo transfer (P/ET), in nulliparous Holstein heifers. Heifers in experiment 1 were randomly assigned to receive no treatment (control; n = 129) or 2,000 IU of hCG 7 d after AI to a detected estrus (estrus = experimental d 0; hCG; n = 132). Heifers in experiment 2 were randomly assigned to receive no treatment (control; n = 143) or 2,000 IU of hCG (hCG; n = 148) at transfer of an IVF embryo 7 d after the last GnRH treatment of a 5-d controlled internal drug release-synch protocol (last GnRH = experimental d 0). Blood samples were collected from a subgroup of heifers (experiment 1, n = 82; experiment 2, n = 104) at d 7, 11, 18, 20, 25, 28, and 32, and blood samples from heifers diagnosed pregnant were collected on d 35, 39, 46, 53, 60, and 67. Blood samples were assayed for P4 by RIA and for PSPB by ELISA, and expression of ISG15 was assessed in mRNA isolated from blood leukocytes on d 18 and 20. Data were analyzed by ANOVA and logistic regression using the MIXED and GLIMMIX procedures. In both experiments, treatment with hCG increased P4 concentrations from d 11 to 32; however, treatment did not affect P/AI or P/ET at d 32 or 67, PSPB concentrations from d 11 to 67 of pregnancy, or relative ISG15 mRNA concentrations on d 18 or 20. Heifers diagnosed not pregnant at d 32 in experiment 2 with an extended luteal phase (>20 d) and treated with hCG had greater relative ISG15 mRNA concentrations on d 20 than control heifers. Treatment with hCG did not affect pregnancy loss in experiment 1, whereas heifers treated with hCG at the time of IVF embryo transfer had fewer pregnancy losses from d 32 to 67 than control heifers. We concluded that treatment with 2,000 IU of hCG 7 d after AI or at the time of embryo transfer increased P4 concentrations without affecting P/AI or P/ET in nulliparous Holstein heifers.

Asunto(s)

Bovinos/fisiología , Gonadotropina Coriónica/administración & dosificación , Transferencia de Embrión/veterinaria , Inseminación Artificial/veterinaria , Resultado del Embarazo/veterinaria , Animales , Citocinas/genética , Transferencia de Embrión/métodos , Estro , Detección del Estro , Sincronización del Estro/métodos , Femenino , Fertilización In Vitro/veterinaria , Hormona Liberadora de Gonadotropina/administración & dosificación , Humanos , Paridad , Embarazo , Progesterona/sangre , ARN Mensajero/sangre

RESUMEN

PURPOSE: The prognosis is poor for patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC. A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, previously treated EOC. PATIENTS AND METHODS: This study was designed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent, platinum-resistant, previously treated ovarian, peritoneal, or fallopian tube cancer. Here, 50mg cyclophosphamide were combined with 400 to 800mg pazopanib daily. RESULTS: Sixteen patients were treated; mean age was 66years. At dose levels (DL) I and II, one instance of dose-limiting toxicity (DLT) was seen in one of 6 patients. At DL III, two of four patients showed a DLT, leading to a maximum tolerated dose (MTD) of 600mg pazopanib daily. Median number of administered cycles was 6 (2-13), with three patients being treated for at least 13months. Median progression-free survival (PFS) and overall survival (OS) were 8.35months and 24.95months, respectively. 155 adverse events (AE) occurred, most frequently elevation of liver enzymes, leukopenia, diarrhea and fatigue. Altogether, five serious adverse events (SAE) developed in four patients. CONCLUSION: Pazopanib 600mg daily p.o. and metronomic cyclophosphamide 50mg daily p.o. is a feasible regimen for patients with recurrent platinum-resistant EOC and showed promising activity in this previously treated patient population. TRIAL REGISTRATION: Clin.trial.gov registry no.: NCT01238770.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Quísticas, Mucinosas y Serosas/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Anciano , Carcinoma Epitelial de Ovario , Ciclofosfamida/administración & dosificación , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Fatiga/inducido químicamente , Femenino , Humanos , Indazoles , Leucopenia/inducido químicamente , Pruebas de Función Hepática , Dosis Máxima Tolerada , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Compuestos de Platino , Pirimidinas/administración & dosificación , Sulfonamidas/administración & dosificación

RESUMEN

Exercise training has been firmly established as an additional therapeutic strategy in addition to pharmacological and interventional treatment in patients with cardiovascular disease. Benefits for quality of life as well as prognosis have been confirmed for cardiovascular risk factors, ischemic heart disease, after myocardial infarction, in heart failure with preserved as well as reduced ejection fraction, in atrial fibrillation and in patients after catheter-assisted aortic valve implantation (TAVI), with an implantable cardioverter defibrillator (ICD) or with left ventricular assist devices (VAD). Training programs have to be tailored according to the disease, stage of disease, comorbidities, age of the patient, medication as well as exercise capacity. For prescribing exercise mode and intensity, a maximum exercise test has to be performed. Ideally, this is accompanied by spirometry to assess maximum values such as maximum oxygen consumption. Training intensity will then be prescribed according to the optimal training range and maximum training intensity.

Asunto(s)

Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Terapia por Ejercicio/métodos , Terapia por Ejercicio/tendencias , Predicción , Medicina Basada en la Evidencia , Humanos , Espirometría/métodos , Resultado del Tratamiento

RESUMEN

Introduction: Intradermal periareolar injection technique for sentinel lymph node biopsy (SLNB) may offer an advantage by including multifocal breast cancer as an additional indication. In May 2008 we changed our standard procedure from peritumoral (PT) to periareolar (PA) injection. We compared the results for corresponding periods before and after the change in procedure. Material and Method: A total of 117 patients (pts.) were investigated the year after we changed our technique; a total of 152 pts were investigated in the reference period 2007. We investigated the identification rates for sentinel lymph nodes (SLN) identified scintigraphically and surgically as well as the rates of metastatic involvement (LN). Results: After PT injection, scintigraphic detection of SLN failed in 5/152 pts., and in a further 10 pts. SLN was not found at surgery. In 7 of 15 pts. in whom SLN was not detected, histology demonstrated nodal involvement. Metastases were found in the SLN of 28 of 137 pts. with successful detection of SLN; no other lymph nodes were affected in 21 of these pts. (75.0 % of pts. with positive SLN detection). With PA injection at least one SLN could always be detected using scintigraphy; only 2/117 SLN could not be found intraoperatively. Metastasis was found in SLN in 34/115 pts.; in 19/34 pts., metastatic involvement was limited to the SLN with no other lymph nodes involved (55.9 % of pts. with positive detection of SLN). Discussion: The detection rate for SLN was significantly higher using PA injection (98.3 % vs. 90.1 %). As axillary dissection was not done in SLN-negative patients, rates of false-negative detection cannot be determined. PA injection not only results in better detection rates, it also offers the advantage that the technique can be performed correctly regardless of tumour localisation.

RESUMEN

We have investigated the phenomenon of flow-induced aggregation in highly concentrated colloidal dispersions exposed to strongly converging flow fields. This phenomenon is relevant not only for classical technical operations like coating, pumping or filtration, but also for the application of concentrated suspensions in upcoming processing technologies based on microfluidic devices. A ring-slit device (gap height 10-25 µm), which allows for a variation of flow kinematics in a wide range, has been developed in order to investigate this phenomenon. Various polymer dispersions with different particle surface properties have been used as model systems. Our experiments exclude, that channel clogging is due to retention of pre-existing aggregates, fouling or hydrodynamic bridging. Instead, we demonstrate that clogging of the microchannel is induced by hetero-coagulation between primary colloidal particles and micron-sized impurities present at concentrations on the order of 100-1000 ppm. Clogging can occur even if the diameter of these impurities is less than a tenth of the gap height. Aggregation takes place in the converging flow field at the channel entrance, but not in the shear field within the slit. It can be suppressed by appropriate stabilization of the primary particles.

Asunto(s)

Técnicas Analíticas Microfluídicas , Nanopartículas/química , Coloides/química , Tamaño de la Partícula , Reología , Propiedades de Superficie

RESUMEN

Recently, there has been increasing evidence that a non-synonymous exchange (Gly307Ser) in the gene for CD226 is linked to several autoimmune diseases including type 1 diabetes, multiple sclerosis (MS), rheumatoid arthritis and Grave's disease. Here we present evidence that this polymorphism also predisposes to Wegener's granulomatosis (WG), an autoimmune condition belonging to the group of ANCA (antineutrophil cytoplasmic autoantibody)-associated vasculitides. We found a significant association of the 307Ser allele in separate panels of 520 Northern German (P=0.016, odds ratio (OR)=1.20) and 122 Southern German (P=0.020, OR=1.37) WG cases compared with 1226 healthy controls. The importance of this single-nucleotide polymorphism in the etiopathology of ANCA-associated vasculitides is supported by similar effect sizes that we found in British WG cases (n=105) and German patients with Churg-Strauss syndrome (n=119), which, however, miss significance level because of the relatively small cohorts available for these rare disorders. Finally, we confirm the association with MS in a cohort of 422 German patients (P=0.011, OR=1.23).

Asunto(s)

Antígenos de Diferenciación de Linfocitos T/genética , Síndrome de Churg-Strauss/genética , Granulomatosis con Poliangitis/genética , Esclerosis Múltiple/genética , Polimorfismo de Nucleótido Simple/genética , Estudios de Casos y Controles , Síndrome de Churg-Strauss/epidemiología , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Alemania/epidemiología , Granulomatosis con Poliangitis/epidemiología , Haplotipos/genética , Humanos , Masculino , Esclerosis Múltiple/epidemiología , Pronóstico

RESUMEN

IR/R2PI-spectroscopy has been applied to the electronic ground and electronically excited states of 3-hydroxyflavone (3-HF) and 2-(2-naphthyl)-3-hydroxychromone (2-NHC) in a supersonic jet yielding direct structural information on the educt and product of a proton transfer reaction. We show that IR spectra of the electronically excited states can be recorded subsequent to a photoinduced chemical reaction, in this case a proton transfer. In combination with DFT and TDDFT calculations structural assignments are performed.

Asunto(s)

Cromonas/química , Flavonoides/química , Naftalenos/química , Espectrofotometría Infrarroja/métodos , Estructura Molecular , Protones , Teoría Cuántica , Espectrofotometría Ultravioleta/métodos

RESUMEN

Between 1996 and 2004, a total of 708 patients were enrolled in the acute myeloid leukaemia (AML) '96 and '02 studies of the East German Study Group (OSHO). Of these, 138 patients (19.5%) had unfavourable cytogenetics defined as complex karyotype, del (5q)/-5, del (7q)/-7, abn (3q26) and abn (11q23). In all, 77 (56%) achieved complete remission 1 (CR1) after induction chemotherapy and were eligible for haematopoietic cell transplantation (HCT). HCT was performed after a median of two cycles of consolidation chemotherapy (CT) in the AML '96 and one cycle in the AML '02 study (P=0.03). After a median follow-up of 19 months, overall survival (OS) at two years was significantly better in the donor group (52+/-9%) versus the no-donor group (24+/-8%; P=0.005). Differences in outcomes were mainly because of a lower relapse incidence in patients after HCT (39+/-11%) compared with a higher relapse incidence in patients undergoing CT (77+/-10%; P=0.0005). Treatment-related mortality was low and not statistically significantly different between the two treatment groups (15+/-7 and 5+/-5% for HCT and chemotherapy, respectively; P=0.49).We conclude that early HCT from related or unrelated donors led to significantly better OS and leukaemia-free survival compared with chemotherapy in patients with unfavourable karyotype.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/mortalidad , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Cariotipificación , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Tasa de Supervivencia , Trasplante Homólogo , Adulto Joven

RESUMEN

AIM: In non-diabetic patients, sympathetic innervation can be preserved even if there is major impairment of myocardial blood supply. Matters may be more complex in diabetic patients because denervation can be caused by cardiac autonomic neuropathy (CAN) or by ischemic injury. Our aim was to determine whether restrictions in myocardial blood supply have a pronounced influence on sympathetic innervation in diabetics and if this effect can be differentiated from CAN. PATIENTS, METHODS: We analyzed 20 diabetics with advanced coronary artery disease (CAD) and without known CAN. We determined quantitative myocardial blood flow using (13)N-ammonia-PET, myocardial viability with (18)F-FDG, and cardiac innervation with (11)C-HED. We investigated the relationship between regional HED retention, blood flow, and coronary flow reserve (CFR). Attenuated heart rate response to adenosine was taken as indicator for CAN (HR ratio). RESULTS: There was minor correlation of segmental stress flow and HED retention (r(2)=0.063, p<0.0001). Correlation improved when stress flow as well as HED retention were normalized to the individual maximum (r(2)=0.162, p<0.0001). In nine patients, a HR ratio <1.2 implicated subclinical CAN. Duration of diabetic disease or glycaemic control (HbA1c) did not correlate with mean HED retention in the viable segments, but with its variation coefficient. CONCLUSIONS: As in non-diabetic patients, a slight correlation exists between CFR and sympathetic innervation. The sensitivity of sympathetic nerves to reductions in CFR does not seem to be increased as compared to the results reported for non-diabetics. Besides impaired blood supply, long duration of diabetic disease and bad glycaemic control also seem to impair sympathetic innervation provoking higher heterogeneity.

Asunto(s)

Circulación Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Angiopatías Diabéticas/diagnóstico por imagen , Fluorodesoxiglucosa F18/farmacocinética , Sistema de Conducción Cardíaco/diagnóstico por imagen , Edad de Inicio , Anciano , Transporte Biológico , Femenino , Técnica de Clampeo de la Glucosa , Hemoglobina Glucada/metabolismo , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Análisis de Regresión

RESUMEN

In this paper the structure of the isolated tetrapeptide model Ac-Leu-Val-Tyr(Me)-NHMe (Leu = leucine, Val = valine, Tyr = tyrosine) is investigated by mass- and isomer-selective IR/UV double resonance spectroscopy. Two isomers of this peptide are observed and in combination with force field, ab initio, and DFT calculations these structures are assigned to folded arrangements presenting two different secondary structure binding motifs: (a) a combined gamma-turn/beta-turn structure and (b) a triple gamma-turn structure, which is described for the first time for an isolated model system in the gas phase.

Asunto(s)

Oligopéptidos/química , Secuencias de Aminoácidos , Sitios de Unión , Isomerismo , Espectrometría de Masas , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta

RESUMEN

A 42-year-old female patient with acute myeloid leukemia presented with fever and heavy chest pain after her first cycle of specific chemotherapy. Acute myocardial infarction was excluded, but surprisingly, parasitic inclusions in erythrocytes became obvious in Pappenheim and Giemsa-stained peripheral blood smears. The patient did not remember a tick bite but acknowledged having received several blood transfusions in her recent medical history. Suspicion of malaria was ruled out by use of a dip-stick test. The diagnosis of Babesia microti infection was finally established by specific polymerase chain reaction (PCR). Six weeks after initiation of specific treatment, PCR turned negative and a positive immunoflourescence assay (IFA) with an IgG titer of 1:128 indicated seroconversion. Subsequent screening of donors involved in the transfusion of blood products to the patient demonstrated borderline reactivity for Babesia microti (IgG-titer 1:32) in 1 out of 44 individuals. Neither the patient nor the positively tested blood donor had travelled to North America or Asia. Therefore, this is the first confirmed autochthonous human infection in Europe.

Asunto(s)

Babesia microti/patogenicidad , Babesiosis/diagnóstico , Reacción a la Transfusión , Zoonosis/transmisión , Enfermedad Aguda , Adulto , Animales , Babesiosis/epidemiología , Babesiosis/genética , Donantes de Sangre , Femenino , Furanos , Alemania , Humanos , Leucemia Mieloide , Tiofenos

RESUMEN

In this communication we report on the conformational analysis of side-chains in the beta-sheet model system (Ac-Phe-OMe)(2) by applying IR/R2PI (infrared/resonant 2-photon ionisation) spectroscopy in the fingerprint region up to 10 microm, where in order to get information in this spectral region an extension of our new high energy and narrow band-width nanosecond IR laser system is presented.

Asunto(s)

Aminoácidos/química , Péptidos/química , Gases , Modelos Moleculares

RESUMEN

PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Linfoma Folicular/mortalidad , Linfoma de Células del Manto/mortalidad , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Compuestos de Mostaza Nitrogenada/administración & dosificación , Prednisona/administración & dosificación , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación

RESUMEN

Inflammatory bowel diseases (IBD) are multifactorial disorders characterised by the host's inability to limit the inflammatory response to luminal antigens. The association of polymorphisms in the CARD15 gene with Crohn's disease (CD) demonstrates the relevance of activated transcription factor NF(kappa)B in mononuclear cells. Interleukin 11 (IL11) mediates anti-inflammatory effects and is able to downregulate LPS-induced NF(kappa)B activation. The IL11 gene is therefore a good candidate involved in genetic predisposition to IBD. To evaluate the role of the IL11 gene in IBD, two polymorphisms, including a dinucleotide repeat in the promoter region, have been genotyped in 222 patients with CD, 152 patients with ulcerative colitis (UC) and 400 healthy controls. PCR-SSCP analysis of the coding region revealed a single polymorphism in exon 4 leading to an amino acid exchange (G335A; R112H), not significantly associated with either disease. Dinucleotide repeat frequencies of the IL11.A1 allele and of IL11.A1 homozygous individuals were significantly increased among the patients with UC (P < 0.002 and (P < 0.003, respectively) but not with CD. Altered expression of IL11 appears to be involved in the genetic predisposition of UC.

Asunto(s)

Colitis Ulcerosa/genética , Interleucina-11/genética , Polimorfismo Genético , Alelos , Repeticiones de Dinucleótido/genética , Genotipo , Humanos , Polimorfismo Conformacional Retorcido-Simple , Regiones Promotoras Genéticas/inmunología

RESUMEN

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.

Asunto(s)

Fluorodesoxiglucosa F18 , Isotretinoína/uso terapéutico , Radiofármacos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/tratamiento farmacológico , Adenocarcinoma/sangre , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma Folicular/sangre , Adenocarcinoma Folicular/diagnóstico por imagen , Adenocarcinoma Folicular/tratamiento farmacológico , Adenocarcinoma Folicular/radioterapia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carcinoma Papilar/sangre , Carcinoma Papilar/diagnóstico por imagen , Carcinoma Papilar/tratamiento farmacológico , Carcinoma Papilar/radioterapia , Quimioterapia Adyuvante , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Persona de Mediana Edad , Radiofármacos/uso terapéutico , Tiroglobulina/sangre , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/radioterapia , Tomografía Computarizada de Emisión

RESUMEN

BACKGROUND: Inflammatory bowel diseases (IBD) are multifactorial disorders, characterized by failure to limit the inflammatory response to luminal antigens. Although genetic factors play an important role in the pathogenesis, little is known about the genes accountable. Immune response to intestinal bacteria seems to be crucial in the pathogenesis of IBD. METHODS: To evaluate the role of the CD14 gene in IBD, a functionally relevant polymorphism in the promoter region (T/C at position -159) has been genotyped in 219 patients with Crohn disease (CD), 142 patients with ulcerative colitis (UC) and 410 healthy controls by RFLP analysis. RESULTS: T allele and TT genotype frequencies were found increased in CD patients compared to controls (Pc=0.044 and 0.005, respectively). CONCLUSION: An altered immune response to LPS seems to play a role in the genetic predisposition to CD but not to UC.

Asunto(s)

Enfermedad de Crohn/genética , Receptores de Lipopolisacáridos/genética , Polimorfismo Genético , Alelos , Estudios de Casos y Controles , Colitis Ulcerosa/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción

RESUMEN

Studies of resting regional cerebral glucose consumption (rCMRGlc) in nondemented patients with Parkinson's disease (PD) have produced conflicting results, reporting both reduced and normal metabolism in advanced disease and reduced or normal metabolism after dopaminergic therapy. To investigate these issues, [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed in 11 nondemented PD patients with advanced disease and 10 age-matched controls. PD patients were studied after withdrawal of all dopaminergic medication to produce a practically defined off condition, and a second time 1 hour after levodopa, resulting in a clinical on state. Dynamic PET scans and simultaneous arterialised venous blood samples of [(18)F] activity were obtained. A graphical approach was used to generate parametric images of rCMRGlc and statistical parametric mapping to localise significant metabolic changes in PD. Compared with controls, global rCMRGlc was reduced in the on but not in the off condition in PD. In both states, significant regional reductions of glucose uptake were found in the parietal, frontal, temporal cortex, and caudate nucleus. Reductions correlated with the severity of disability in frontal and temporal cortex. Direct comparison between on and off conditions revealed relatively greater reductions of uptake in the ventral/orbital frontal cortex and the thalamus during on. Results suggest that cortical and caudate hypometabolism are common in advanced PD and that caution is mandatory if [(18)F]FDG PET is being used to differentiate advanced PD from dementia and progressive supranuclear palsy where similar reductions are seen. Furthermore, in PD, administration of levodopa is associated with further hypometabolism in orbitofrontal cortex; an area known to be relevant for reversal learning where performance is typically impaired after dopaminergic treatment.

Asunto(s)

Antiparkinsonianos/efectos adversos , Corteza Cerebral/efectos de los fármacos , Glucosa/metabolismo , Levodopa/efectos adversos , Enfermedad de Parkinson/metabolismo , Tomografía Computarizada de Emisión , Adulto , Estudios de Casos y Controles , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico por imagen , Valor Predictivo de las Pruebas , Radiofármacos , Índice de Severidad de la Enfermedad , Tomografía Computarizada de Emisión/métodos

RESUMEN

Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg-Strauss syndrome (CSS) are characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Anti-myeloperoxidase (MPO)-ANCA are a typical feature of MP and CSS, while anti-proteinase 3 (PRTN3)-ANCA are highly specific for WG. Several reports indicate that ANCA may directly contribute to pathological processes, ie, through an increase of adhesivity between polymorphonuclear (PMN) and endothelial cells (EC). PMN interact and endothelium interact via the adhesion cascade (AC). CD18 is a key molecule of the AC, as CD18 defects abrogate the adhesion of PMN and cause leukocyte adhesion deficiency, an immunodeficient trait. We have screened the entire coding and regulatory regions of the CD18 gene. Ten single nucleotide polymorphisms (SNP) were identified, four of them showing significant associations with MPO-ANCA(+) vasculitis. One of these SNP's was localized in an alternate transcription initiation site. This polymorphism may influence CD18 gene expression, resulting in dose-dependent increase in adhesion and consecutively facilitated degranulation and respiratory burst. In this manner the pro-adherent genotype may predispose to MPO-ANCA(+) vasculitis.

Asunto(s)

Anticuerpos Anticitoplasma de Neutrófilos/biosíntesis , Antígenos CD18/genética , Peroxidasa/inmunología , Polimorfismo de Nucleótido Simple/genética , Vasculitis/genética , Secuencia de Bases/genética , Exones/genética , Predisposición Genética a la Enfermedad/etiología , Predisposición Genética a la Enfermedad/genética , Humanos , Datos de Secuencia Molecular , Mieloblastina , Reproducibilidad de los Resultados , Serina Endopeptidasas/genética , Vasculitis/etiología , Vasculitis/inmunología