Expression of CD47 antigen in Reed-Sternberg cells as a new potential biomarker for classical Hodgkin lymphoma.

INTRODUCTION: CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRPalpha on macrophages inhibiting phagocytic signal, providing a survival advantage to tumor. CD47, therefore, represents a valuable target for immunotherapy and is currently under clinical investigation. We aimed to study CD47 expression in Hodgkin Reed Sternberg cells (HRS). METHODS: We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 16 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (8 Female, 8 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were nodular sclerosis in 11 cases, mixed Cellularity in 3 cases and lymphocyte rich in 2 additional cases. Median age was 53 years (Range: 8, 74). Early stage disease was found in three patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and nine patients had advanced disease. Bulk disease was present in one patient. Normal lymphoid tissue and normal prostate epithelium were used as normal controls as recommended by manufacturer. Approval from the Local Ethical committee was obtained before any analysis. RESULTS: CD47 was overexpressed on all HRS cells with a characteristic dot-like pattern in 13/13 cases of CHL. HRS clearly expressed CD47 more intensely than infiltrating T and stromal cells. DISCUSSION: We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth, which could be circumvented using blocking monoclonal antibodies.

Plant attributes and their relationship to the germination response to different temperatures of 18 species from central Mexico.

Germination responses of non-dormant seeds to temperature and thermal requirements are affected by the geoclimatic origin of the species, along with specific attributes such as life form, life cycle or seed size. We evaluated the relationship of these attributes and temperature to germination in 18 species that inhabit a convergence area of two biogeographic realms. Seeds were sown at different constant temperatures. Base temperature (Tb ) and thermal time for 50% germination (θT(50) ) were determined. For Tb , θT(50) and seed size, we performed a cluster analysis and then applied a discriminant analysis (DA). DA was also performed using geoclimatic origin, life form and life cycle as grouping variables. Seed that did not germinate were transferred to the benefit temperature for germination. Finally, ethylene was applied to the remaining seeds that did not germinate. Temperature significantly affected final germination. Tb varied between 5 and 13 °C in 15 species and 19.0-21.5 °C in the remainder; θT(50) was 7-30 °Cd in eight species and 50-109 °Cd in the remainder. Cluster analysis showed three groups, and DA evidenced the relevance of Tb and θT(50) for this separation. Differences in life cycle were related to θT(50) . The geoclimatic origin was not significant. Thermoinhibition or thermodormancy were found in some species. Tb overlaps with environmental temperature of the growth season. Thermal traits for germination mainly reflect the species' life cycle, which is related to the main differences in reproductive performance among annuals and perennials. Local adaptation might mask the effect of geoclimatic origin of a species.

Metastatic neuroblastoma in infants: are survival rates excellent only within the stringent framework of clinical trials?

INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.

[Minimally invasive treatment of chronic subdural hematoma in adults. Results in 116 patients]. / Tratamiento mínimamente invasivo del hematoma subdural crónico del adulto. Resultados en 116 pacientes.

INTRODUCTION: Chronic subdural hematoma in adults (CSDH) has a global crude incidence of 14.1/100,000 per year in our institution captive population. There is no single treatment protocol. In our hospital we choose a minimal invasive technique (trans-marrow puncture) without general anaesthesia due to the age of the population. A descriptive study of patients with CSDH and treatment results, including a laterality analysis, is presented. MATERIAL AND METHODS: We retrospectively searched patients with (CSDH) between January 1998 and May 2009. The diagnosis was made by neuroimaging techniques in all patients. The preferred treatment was trans-marrow puncture; exceptionally some patients were treated by burr holes or craniotomy. RESULTS: We found 127 patients. Age, gender, midline displacement, hospitalisation days, and number of procedures, were not a predictive factor of mortality in the first month. A slight majority (55%) of CSDH were on the left side, with no statistically significant difference. There were 6 (4.7%) deaths during hospitalisation. In our series cumulative mortality at six months was 11.8%. Markwalder scale at admission was not a predictive factor of statistically significant mortality. An 80% of the patients received trans-marrow puncture as single procedure was performed on 80% of the patients. CONCLUSIONS: The results of our study suggest that trans-marrow puncture is an acceptable procedure, with low mortality, and less hospitalisation days and complications. Mortality, associated mechanisms, age, gender, midline displacement are no different than in others previous publications. We found a higher frequency of hematomas to the left, as in other series. Meta-analysis studied need to be performed to determine more accurately the frequency of this dominance.

[The effect of a fibre enriched dietary milk product in chronic primary idiopatic constipation]. / Efecto de la ingesta de un preparado lácteo con fibra dietética sobre el estreñimiento crónico primario idiopático.

BACKGROUND: fibre is effective in some types of constipation. Our objective was to determine if the administration of an enriched dairy preparation with a supplement of soluble fibre (Naturfibra) [inulin and digestion resistant maltodextrin (Fibersol 2)], improves primary chronic constipation. METHODS: Prospective, randomized, double blind clinical trial randomized with dietary intervention in 32 subjects with constipation according to the Rome II criteria. Thirty two subjects (men 4; women 28) with an average age of 47 +/- 15 years were randomly divided in two homogeneous groups. A type of milk (A or B) was assigned to each group. Group A received fibre enriched semi-skimmed milk; Group B received semi skimmed milk. The subjects drank half a litre of milk per day during 20 days, meaning that those who drank the enriched milk ingested 20 grams of fibre a day. RESULTS: The subjects that presented straining at defecation (p < 0.001), sensation of incomplete evacuation (p < 0.001), sensation of obstruction in the evacuation (p < 0.001) and days between bowel movements, diminished significantly after the intake of milk supplemented with fibre. CONCLUSION: The intake of a dairy preparation with a supplement of fibre containing 20 grams of soluble fibre (inulin and digestion resistant maltodextrin), improves the situation of idiopathic primary chronic constipation based on the Rome II criteria.

The effects of an antioxidant-supplemented beverage on exercise-induced oxidative stress: results from a placebo-controlled double-blind study in cyclists.

The objective of this study was to test the effects of an antioxidant-supplemented beverage on exercise-induced oxidative stress in moderately trained cyclists. A double-blind study was conducted in moderately trained cyclists. They were randomly allocated to receive either an antioxidant (13 subjects) or a placebo (13 subjects) 15 min pre-exercise (30 ml.kg(-1)) and during a 90 min constant-load test (30 ml.kg(-1).15 min(-1)) on a bicycle ergometer at 70% VO2max The supplemented beverage contained black grape (81 g/l), raspberry (93 g/l) and red currant (39 g/l) concentrates, and its total antioxidant capacity, measured by the ABTS(.+) technique, was 0.41 mM Trolox. No significant difference from basal to post-exercise period was detected for plasma TBARS in either the placebo group or the group receiving the antioxidant supplemented beverage. Post-exercise carbonyls decreased by 29% in the group receiving antioxidants, and the pattern of change was significantly different between antioxidant and placebo conditions. The urinary excretion of 8-OHdG increased significantly by 21% in the placebo group. Again differences in the pre- to post-exercise change were significant between both conditions These results suggest that in moderately trained cyclists, antioxidant supplementation counters oxidative stress induced by a 90 min exercise at 70% VO2max.

A cytochrome c variant resistant to heme degradation by hydrogen peroxide.

BACKGROUND: Cytochrome c has peroxidase-like activity and can catalyze the oxidation of a variety of organic substrates, including aromatic, organosulfur and lipid compounds. Like peroxidases, cytochrome c is inactivated by hydrogen peroxide. During this inactivation the heme prosthetic group is destroyed. RESULTS: Variants of the iso-1-cytochrome c were constructed by site-directed mutagenesis and were found to be more stable in the presence of hydrogen peroxide than the wild type. No heme destruction was detected in a triple variant (Tyr67-->Phe/Asn52-->Ile/Cys102-->Thr) with the catalytic hydrogen peroxide concentration of 1 mM, even following the loss of catalytic activity, whereas both double variants Tyr67-->Phe/Cys102-->Thr and Asn52-->Ile/Cys102-->Thr showed a greater rate of peroxide-induced heme destruction than observed with the wild-type protein. CONCLUSIONS: Heme destruction and catalytic inactivation are two independent processes. An internal water molecule (Wat166) is shown to be important in the heme destruction process. The absence of a protein radical in the resistant variant suggests that the protein radical is necessary in the heme destruction process, but presumably is not involved in the reactions leading up to the protein inactivation.

Cardiorespiratory fitness, glycemic status, and mortality risk in men.

OBJECTIVE: To determine the association of baseline cardiorespiratory fitness to all-cause mortality across the range of blood glucose levels. RESEARCH DESIGN AND METHODS: Data from a prospective study of 8715 men (average age 42 yr), followed for an average of 8.2 yr (range 1-15 yr), were analyzed. Cardiorespiratory fitness was assessed by maximal-exercise treadmill testing. Men with evidence of clinical vascular disease or who did not achieve 85% of their age-predicted maximum heart rate during exercise testing were excluded from analyses. RESULTS: Age-adjusted death rates increased with higher levels, of fasting blood glucose. Regardless of glycemic status, fit men had lower age-adjusted all-cause death rates than their less fit counterparts. For men with fasting blood glucose greater than or equal to 7.8 mM or physician-diagnosed non-insulin-dependent diabetes mellitus (NIDDM), the age-adjusted death rates per 10,000 person-yr of follow-up in unfit and fit subjects were 82.5 and 45.9, respectively. The age-adjusted relative risk of death due to all causes was significantly elevated in the lower-fitness group within each of three glycemic status levels: fasting blood glucose less than 6.4 mM; relative risk (RR) = 1.93 (95% confidence interval [95% CI] 1.15-3.26); fasting blood glucose 6.4-7.8 mM; RR = 3.42 (95% CI 2.27-5.15); and fasting blood glucose greater than or equal to 7.8 mM or with NIDDM, RR = 1.80 (95% CI = 1.25-2.58). Multivariate analyses, controlling for risk factors of mortality (age, resting systolic blood pressure, serum cholesterol, body mass index, family history of heart disease, follow-up interval, and smoking habit) showed a higher risk of death due to all causes for unfit compared with fit men. Multivariate risks of death associated with low fitness, compared with higher fitness (RR), in the three glycemic status groups were: fasting blood glucose less than 6.4 mM, RR = 1.38 (95% CI 1.09-1.74); fasting blood glucose 6.4-7.8 mM, RR = 1.61 (95% CI 0.91-2.86); and fasting blood glucose greater than or equal to 7.8 mM or with NIDDM, RR = 1.92 (95% CI 0.75-4.90).

[Pancreatic fistula]. / Fistulas pancreáticas.

The authors present the result of an investigation on the use of cement and bentonite in the treatment of pancreatic fistulas that coexisted with permeable duct and which has been closed by the local application of said elements.