Measuring quantitative proteomic distance between Spanish beef breeds.

Estimates of quantitative proteomic distance between populations have not been reported to date. Here, quantitative proteomic distances between three Spanish bovine breeds (Asturiana de los Valles, AV; Retinta, RE; and Rubia Gallega, RG) were estimated from two-dimensional electrophoresis profiles of meat samples of longissimus thoracis muscle at 2 h post-mortem. Statistically significant distances were detected between AV/RG and the most genetically different RE breed, using the novel QD measure of quantitative proteomic distance. In total, 18 differentially abundant myofibrillar and sarcoplasmic proteins/isoforms contributing to proteomic distances between breeds were confidently identified by tandem mass spectrometry. The fast skeletal myosin regulatory light chain 2 followed by other five interacting proteins exhibited the most pronounced relative change between breeds. In addition, most differentially represented proteins could be associated with variations in meat tenderness. Therefore, they could be candidate biomarkers for molecular breeding programs and authentication of the three Spanish beef breeds.

Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients.

Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS). Results: A total of 683 patients were identified. Baseline characteristics were similar in the ibrutinib and idelalisib groups. ORR to ibrutinib and idelalisib as first KI was 69% and 81%, respectively. With a median follow-up of 17 months (range 1-60), median PFS and OS for the entire cohort were 35 months and not reached. Patients treated with ibrutinib (versus idelalisib) as first KI had a significantly better PFS in all settings; front-line [hazard ratios (HR) 2.8, CI 1.3-6.3, P = 0.01], relapsed-refractory (HR 2.8, CI 1.9-4.1, P < 0.001), del17p (HR 2.0, CI 1.2-3.4, P = 0.008), and complex karyotype (HR 2.5, CI 1.2-5.2, P = 0.02). At the time of initial KI failure, use of an alternate KI or venetoclax had a superior PFS when compared with chemoimmunotherapy. Furthermore, patients who discontinued ibrutinib due to progression or toxicity had marginally improved outcomes if they received venetoclax (ORR 79%) versus idelalisib (ORR 46%) (PFS HR .6, CI.3-1.0, P = 0.06). Conclusions: In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms.

Watermelon stomach, hemorrhagic pericarditis, small cell carcinoma of the lung and synchronous squamous cell carcinoma of the tongue base.

Based on a case of gastric antral vascular ectasia (watermelon stomach) that was associated with hemorrhagic pericarditis, small cell lung carcinoma with mediastinal lymph node metastases and a synchronous squamous cell carcinoma of the base of the tongue, the authors made a review of the clinical, endoscopic and histopathological aspects of this type of gastropathy, and its association with other diseases, and of the results of its endoscopic therapy. The causes of hemorrhagic pericarditis are considered, emphasizing the necessity to know if the effusion has a malignant etiology. To the best of our knowledge the association of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of the base of the tongue has not yet been described. Extensive metastases to mediastal lymph nodes are common to small cell lung carcinoma.

Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain.

OBJECTIVE: Toxic thyroid adenoma (TA) is a common cause of hyperthyroidism. Mutations in the TSH receptor (TSHR) gene, and less frequently in the adenylate cyclase-stimulating G alpha protein (GNAS) gene, are well established causes of TA in Europe. However, genetic causes of TA remain unknown in a small percentage of cases. We report the first study to investigate mutations in TSHR, GNAS, protein kinase, cAMP-dependent, regulatory, type I alpha (PRKAR1A) and RAS genes, in a large series of TA from Galicia, an iodine-deficient region in NW Spain. DESIGN AND METHODS: Eighty-five TA samples were obtained surgically from 77 hyperthyroid patients, operated on for treatment of non-autoimmune toxic nodular goitre. After DNA extraction, all coding exons of TSHR, GNAS and PRKAR1A genes, and exons 2 and 3 of HRAS, KRAS and NRAS were amplified by PCR and sequenced. Previously unreported mutants were cloned in expression vectors and their basal constitutive activities were determined by quantification of cAMP response element (CRE)-luciferase activity in CO7 cells transfected with wild-type and mutant plasmids. RESULTS: TSHR gene mutations were found in 52 (61.2%) samples, GNAS gene mutations in 4 (4.71%) samples and no PRKAR1A or RAS mutations were found. Only three previously unreported mutations were found, two affecting the TSHR, A623F and I635V, and one affecting the G-protein alpha-subunit (Gsalpha), L203P. All mutant proteins showed higher CRE-luciferase activity than their wild-type counterparts. CONCLUSIONS: TA in a hyperthyroid population living in Galicia, a Spanish iodine-deficient region, harbours elevated frequencies of TSHR and GNAS mutations activating the cAMP pathway. However, the genetic cause of TA was undetermined in 34% of the TA samples.

Prevalence, awareness, treatment and control of hypertension in Galicia (Spain) and association with related diseases.

The present study evaluated the prevalence of hypertension (HT) and its possible relationships with various risk factors in a representative sample (n=2884) of the adult population (>18 years old) of Galicia, a region of Spain. Subjects were selected by a two-step cluster sampling procedure from the Galician public health service database, which covers more than 95% of the population (2.7 million inhabitants). The overall prevalence of HT, defined as BP >140/90 mm Hg and/or current treatment with antihypertensive medication, was 25.5%, higher in men (31.1%) than in women (20.7%). Of the hypertensive subjects 50.6% were aware of the HT; of these, 72.0% were receiving treatment and 36.4% were treated and controlled. The prevalence of HT increased with age and was higher in subjects from urban areas than rural areas and higher in subjects with low educational level. Surprisingly, people with low educational level more frequently showed awareness of HT than people with high education level. Increased body mass index was related to increased prevalence of HT and close associations were observed between HT and cardiovascular diseases. Our data also show a linear upward trend in blood pressure from normal glucose metabolism to diabetes mellitus. Surprisingly, the prevalence of HT among people with known diabetes was higher than among people with undetected diabetes, which may indicate poor control of HT in diabetic subjects.

Autologous stem cell transplant in ALL: who should we be transplanting in first remission?

Long-term disease-free survival (DFS) has been reported after autologous stem cell transplantation for acute lymphoblastic leukemia. Phase II studies have evaluated its role in first and subsequent complete remission (CR) with DFS rates of up to 50%. It has been under-utilized in 1st CR in part, due to a concern that patients who relapse after autologous stem cell transplantation (ASCT) have fewer options for salvage treatment of relapsed disease. Unfortunately, survival rates of <5% are reported in patients who relapse, regardless of initial therapy. Few prospective, randomized trials have analyzed large enough numbers of patients to allow us to determine the appropriate patient population for autologous transplantation. Although variability in the available studies makes it difficult to draw a definite conclusion, and many issues remain unresolved, available data suggests that there may be a group of patients for whom ASCT in first remission is a reasonable and perhaps superior treatment choice. Factors such as risk features at diagnosis, and minimal residual disease following induction therapy greatly affect outcome following ASCT. The available data as well as the questions that remain to be answered will be discussed and reviewed.

[Spontaneous resolution of branch retinal vein occlusion in cases with non-ischemic macular edema. Significance of a waiting period before considering treatment with vitrectomy]. / Resolución espontánea en casos de obstrucción venosa de rama retiniana asociada a edema macular no isquémico. Importancia de un período de espera previo al tratamiento mediante vitrectomía.

OBJECTIVES/METHODS: It is well established that some patients with branch retinal vein occlusion undergo a spontaneous resolution after a suitable waiting period. We present a series of 22 patients with initial acuity under 0.2 for whom we allowed three months of observation before considering vitrectomy. RESULTS/CONCLUSIONS: 13% of the patients developed enough spontaneous improvement to be excluded from subsequent treatment. We thus believe a waiting period should be considered before instituting treatment in patients with this particular problem.

Resolución espontánea en casos de obstrucción venosa de rama retiniana asociada a edema macular no isquémico. Importancia de un período de espera previo al tratamiento mediante vitrectomía / Spontaneous resolution of branch retinal vein occlusion in cases with non-ischemic macular edema. Significance of a waiting period before considering treatment with vitrectomy

Objetivo/métodos: En esta comunicación se estudia la posible evolución hacia la resolución espontánea de un porcentaje de los enfermos afectos de obstrucción de rama venosa de la retina (ORVR) tras un tiempo de espera.Se presenta una serie de 22 enfermos afectos de ORVR con visiones iniciales inferiores a 0,2 para los que se respeta un período de tres meses desde el comienzo de síntomas antes de considerar vitrectomía.Resultados/Conclusiones: Un 13% de los enfermos estudiados presentaron una mejoría clínica espontánea suficiente que desaconsejó el tratamiento, por lo que creemos debe considerarse un período de espera previo al tratamiento para este tipo de enfermos (AU)

Objectives/Methods: It is well established that some patients with branch retinal vein occlusion undergo a spontaneous resolution after a suitable waiting period. We present a series of 22 patients with initial acuity under 0.2 for whom we allowed three months of observation before considering vitrectomy. Results/Conclusions: 13% of the patients developed enough spontaneous improvement to be excluded from subsequent treatment. We thus believe a waiting period should be considered before instituting treatment in patients with this particular problem (AU)

[Acromegaly and sleep apnea]. / Acromegalia y apnea del sueño.

OBJECTIVE: Acromegaly is often associated with sleep apnea-hypopnea syndrome (SAHS). The purpose of this study was to understand the prevalence of SAHS in patients with acromegaly and define the characteristics of acromegalic patients with and without SAHS. PATIENTS AND METHODS: The study enrolled 17 patients (11 women and 6 men) residing in the province of Ourense, Spain, who were diagnosed with acromegaly. All patients underwent overnight polysomnography in a sleep laboratory. In addition, growth hormone and insulin-like growth factor 1 levels were assessed. Sixteen of the patients underwent cephalometric study. RESULTS: The average age of the patients was 58 years (95% confidence interval [CI], 52-63). The average body mass index was 31 (95% CI, 29-34) and average neck circumference was 41 (95% CI, 39-43). Ten patients (58.8%) had an apnea-hypopnea index (AHI) greater than 10. Nine had obstructive apnea and one had central apnea. Seven (5 with an AHI>10 and 2 with an AHI<10) reported excessive daytime sleepiness with Epworth scores greater than 10 (41.2%). Five patients (29.4%) were diagnosed with SAHS (AHI>10 and Epworth>10). No correlation was found between an AHI greater than 10 and hormonal activity (P=.082). The mean growth hormone level for patients with an AHI greater than 10 was 4.8 (95% CI, 0.5-9) and the mean for those with an AHI less than 10 was 12 (95% CI, 2-27). Fifty percent of the patients were treated with a somatostatin analog and half of those treated exhibited apnea (P=.302). No cephalometric differences related to the presence of apneas were found. CONCLUSIONS: We found a high prevalence of sleep apneas (58.8%) and SAHS (29.4%), and central apneas were rare. We found no correlation between hormone activity level and the presence of SAHS. The incidence of SAHS was the same in somatostatin analog treated and untreated patients. Cephalometric variables did not distinguish between acromegalic patients with and without SAHS.

Cancer risk around the nuclear power plants of Trillo and Zorita (Spain).

AIM: To investigate the association between cancer risk and proximity of place of residence to the Guadalajara nuclear power plants: Trillo and Zorita. METHODS: Case-control study. Cases were patients admitted with cancer and controls were non-tumorous patients, both admitted to Guadalajara Hospital (period 1988-99). Exposure factor: place of residence (areas within 10, 20, and 30 km of each plant). Odds ratios (ORs) of those areas closest to the plants were calculated with respect to those furthest away; a linear trend analysis was also performed. RESULTS: In the extreme areas in the vicinity of Trillo, an OR of 1.71 was obtained (95% CI 1.15 to 2.53), increasing in magnitude in the subgroup of more radioinducible tumours and in the period considered as post-latency (1997-99). Risk increased linearly with proximity to the two plants, significantly in Trillo (p < 0.01) but not in Zorita (p = 0.19). CONCLUSIONS: There is an association between proximity of residence to Trillo and cancer risk, although the limitations of the study should be kept in mind when interpreting the possible causal relation.

Effect of long-term strength training on glucose metabolism. Implications for individual impact of high lean mass and high fat mass on relationship between BMI and insulin sensitivity.

The aim of this study was to examine the independent effect of high lean mass on glucose metabolism, as well as its consequences on the classic relationship between BMI and insulin sensitivity (SI) in 3 groups: 1) 8 strength-trained males with BMI >27 kg/m2 (athletes); 2) 10 sedentary males with BMI >27 kg/m2 (obese); and 3) 12 sedentary males with BMI 22-25 kg/m2 (control). Body composition was measured with impedance analysis. Iv glucose tolerance test was performed at 09:00 h after overnight fast. Estimation of insulin sensitivity and glucose effectiveness by Minimal Model Approach. Plasma glucose and insulin determination by glucose-oxidase and RIA respectively. BMI and lean mass (LM) were greater in athletes than in controls, but there were no differences in fat mass (FM), basal glucose (Gb), basal insulin (Ib), glucose tolerance (Kg), SI, glucose effectiveness (Sg), acute insulin response to glucose (AIRG) and leptin. Obese showed greater FM, leptin, lb and AIRG than athletes, while SI was lower; BMI, LM, Gb, Kg and Sg were similar. BMI, FM, LM, Ib, AIRG and leptin were lower in controls than in obese, while SI index was greater; Gb, Sg and Kg were similar. We found that: 1) Resistance exercise does not modify glucose effectiveness, but can improve insulin sensitivity through FM reduction (LM augmentation alone has no effect on glucose metabolism); and 2) High BMI causes insulin resistance only if it depends on adipose tissue hypertrophy.

Effect of resistance exercise (body building) training on serum leptin levels in young men. Implications for relationship between body mass index and serum leptin.

UNLABELLED: Available data about the influence of exercise on leptin level are controversial, and there are no studies concerning leptin levels in trained men with low fat mass plus large increase of muscle. 65 healthy young male matched for age were separated in three groups. 1) 25 non-professional body builders; 2) 21 mild overweight sedentary subjects; 3) 19 normal weight sedentary controls. Body composition was determined by bioelectrical impedance. Serum leptin was measured in duplicate by RIA. STATISTICS: Student's t and Pearson's test. Athletes showed similar BMI than overweight subjects: 26.98+/-0.49 vs 27.12+/-0.41 but lower fat mass: 12.53+/-0.96 vs 16.16+/-1.01 % (p=0.0064) and lower leptin: 4.66+/-0.51 vs 7.31+/-0.76 microg/l (p=0.014). Athletes showed higher BMI than controls: 26.98+/-0.49 vs 23.08+/-0.30 (p<0.0001) but similar fat mass: 12.53+/-0.96 vs 12.48+/-0.73% and leptin: 4.66+/-0.51 vs 4.79+0.58 microg/l. Overweight subjects showed higher BMI than controls: 27.12+/-0.41 vs 23.08+/-0.30 (p<0.0001), higher fat mass: 16.16+/-1.01 vs 12.48+/-0.73% (p=0.0064) and higher leptin: 7.31+/-0.76 vs 4.79+/-0.589 microg/l (p=0.014). When leptin was calculated by fat mass no differences were observed between the three groups. There was a significant correlation between leptin and fat mass in all groups. Leptin correlated with BMI in overweight subjects (r=0.438, p=0.0463), but this correlation was not observed either in athletes or in controls. In conclusion 1) regardless of the high BMI characteristic of body builders, no correlation was observed with leptin; 2) trained state induced by resistance exercise does not influence leptin production independently of variations in body composition.

[Differentiated carcinoma of the thyroid gland in an area of endemic goiter. Clinical study and prognostic correlation]. / Carcinoma diferenciado de tiroides en un área de bocio endémico. Estudio clínico y correlación pronóstica.

OBJECTIVE: Differentiated thyroid Carcinoma is a relatively frequent malignant neoplasia with three histologic types: papillary, follicular, and Hürtle cell carcinoma. Although papillary is the most common type, in endemic goitre areas the frequency of follicular type increases. Up to now, the only European studies about clinical aspects of differentiated thyroid carcinoma in endemic goitre areas are those performed in the Bavarian region until 1983. As the province of Orense (assistance zone concerning to the Hospital Virgen del Cristal) is a zone of endemic goitre, we have analyzed clinical presentation features and prognostic correlation factors in patients with differentiated thyroid carcinoma living in this area. DESIGN: Retrospective study. Variables analyzed: 1) Age. 2) Sex. 3) Histologic type. 4) Tumor size. 5) Stage. 6) Presence of multinodular goitre. 7) Posttherapeutic disease persistence. 8) Recurrence. 9) Distant metastases. 10) Death attributed to thyroid carcinoma. PATIENTS: 61 cases of differentiated thyroid carcinoma, detected from 1983 to 1993. Mean follow-up period: 5 years (minimum 1, maximum 21). All patients were treated with total thyroidectomy followed by radioiodine ablation. RESULTS: 67.2% of papillary, 31.2% of follicular and 1.6% of Hürtle cell carcinoma. Male/female ratio: 1/4. Mean age: 48.8 +/- 2.9 (M +/- ESM) in papillary and 55 +/- 3.2 in follicular. Tumor size was smaller in papillary: 2.2 +/- 0.2 vs 6.2 +/- 0.5 cm (p < 0.001). Papillary type was detected more frequently than follicular in stages I, II and III, whereas follicular prevailed in stage IV (p < 0.03). Positive correlation between age and size in papillary: r = 0.393 (p < 0.01) and similar tendency in follicular: r = 0.423 (p = 0.057). Multinodular goitre was more frequent in follicular: 47% vs 25% (p = 0.02). Free of disease cases after treatment: 81% of papillary (p < 0.05) and 42% of follicular. Stage correlated independently with disease persistence after treatment (p = 0.0006). Age was minor in free of disease group: 50.0 +/- 3.8 vs 65.3 +/- 3.8 (p = 0.01). CONCLUSIONS: In our area, papillary is the most common type, but follicular proportion is higher than reported from non endemic goitre areas. PC is a small tumor detected in stage I, whereas FC is large and detected in stage IV. Tumor stage is an independent prognostic factor. Frequent presence of multinodular goitre in patients with differentiated thyroid carcinoma suggests that in zones of endemic goitre, clinical attitude in multinodular goitre and solitary nodule must be similar.

Light and electron microscopic immunocytochemical localization of two major proteins in garlic bulb.

Garlic is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, antidiabetic, and anticoagulant. Two major proteins of 40 KD and 14 KD constituting approximately 96% of total garlic proteins have been recently purified at our Institute. This immunocytochemical and ultrastructural study revealed that the 40 KD protein was localized in the parenchyma sheath cells (PSC) of garlic bulbs, whereas the 14 KD protein was present in the cortical cells (CC). Immunogold electron microscopy study indicated that the 40 KD protein was specifically localized in the globular granules of the cytoplasmic area of PSC. Each globular granule was amorphous and homogenous with membrane limiting its outermost layer. The yellowish color of PSC in freshly cut slices of garlic bulb suggested that PSC may have sulfur-containing compounds such as allicin, the primary contributor of the pungency and medicinal properties of garlic. Ellman's reagent test quantitatively revealed that there were 17.8 n moles sulfhydryl (SH)/ml of 40 KD garlic protein. Microtubule tubulin in mitotic figures from PHA-stimulated human short-term whole blood cultures reacted strongly with antitubulin antibody but reacted negatively with anti-40 KD garlic protein antibodies and therefore was not related to the 40 KD garlic protein immunocytochemically.

Neuroquimica de los estados depresivos: implicancias fisiopatologicas y terapeuticas / Neurochemistry of depressive status: physiopathological and therapeutic implications

El examen psiqufatrico de todo paciente no debe tener un enfoque distinto al que darfa cualquier otro especialista medico. En base a eso, los examenes complementarios son un instrumento valioso para el diagnostico, evolucion pronostico y vulnerabilidad. Se detallan los seguientes estudios neuroqufmicos: M.O.P.E.G., A.V.M., A.H.V., N.A., 5-HT., 5-H.I.A., F.E.A. (metabolitos del triptofano y la fenilalanina) y psiconeuroendocrinos: D.S.T., T.R.H./T.S.H., agonistas neuroamfnicos-S.T.H.. Se diferencian marcadores de estado y de rasgo y se les da aplicacion clfnica y terapeútica.