Palaeoecological data indicates land-use changes across Europe linked to spatial heterogeneity in mortality during the Black Death pandemic.

The Black Death (1347-1352 CE) is the most renowned pandemic in human history, believed by many to have killed half of Europe's population. However, despite advances in ancient DNA research that conclusively identified the pandemic's causative agent (bacterium Yersinia pestis), our knowledge of the Black Death remains limited, based primarily on qualitative remarks in medieval written sources available for some areas of Western Europe. Here, we remedy this situation by applying a pioneering new approach, 'big data palaeoecology', which, starting from palynological data, evaluates the scale of the Black Death's mortality on a regional scale across Europe. We collected pollen data on landscape change from 261 radiocarbon-dated coring sites (lakes and wetlands) located across 19 modern-day European countries. We used two independent methods of analysis to evaluate whether the changes we see in the landscape at the time of the Black Death agree with the hypothesis that a large portion of the population, upwards of half, died within a few years in the 21 historical regions we studied. While we can confirm that the Black Death had a devastating impact in some regions, we found that it had negligible or no impact in others. These inter-regional differences in the Black Death's mortality across Europe demonstrate the significance of cultural, ecological, economic, societal and climatic factors that mediated the dissemination and impact of the disease. The complex interplay of these factors, along with the historical ecology of plague, should be a focus of future research on historical pandemics.

First modern human settlement recorded in the Iberian hinterland occurred during Heinrich Stadial 2 within harsh environmental conditions.

As the south-westernmost region of Europe, the Iberian Peninsula stands as a key area for understanding the process of modern human dispersal into Eurasia. However, the precise timing, ecological setting and cultural context of this process remains controversial concerning its spatiotemporal distribution within the different regions of the peninsula. While traditional models assumed that the whole Iberian hinterland was avoided by modern humans due to ecological factors until the retreat of the Last Glacial Maximum, recent research has demonstrated that hunter-gatherers entered the Iberian interior at least during Solutrean times. We provide a multi-proxy geoarchaeological, chronometric and paleoecological study on human-environment interactions based on the key site of Peña Capón (Guadalajara, Spain). Results show (1) that this site hosts the oldest modern human presence recorded to date in central Iberia, associated to pre-Solutrean cultural traditions around 26,000 years ago, and (2) that this presence occurred during Heinrich Stadial 2 within harsh environmental conditions. These findings demonstrate that this area of the Iberian hinterland was recurrently occupied regardless of climate and environmental variability, thus challenging the widely accepted hypothesis that ecological risk hampered the human settlement of the Iberian interior highlands since the first arrival of modern humans to Southwest Europe.

Tree-ring reconstruction of snow avalanche activity: Does avalanche path selection matter?

In the current context of anthropogenic global warming, one of the purposes of dendrogeomorphic analyses is to provide long and continuous chronologies of mass movements, so as to detect potential trends or shift related to increasing temperatures. However, on documented slopes, the comparison between historical archives and tree-ring records suggests that dendrogeomorphic reconstructions systematically underestimate the natural activity of the process under investigation. In the specific case of snow avalanches, underestimation generally amounts to 50% and the main causes generally given for this difference are related to the magnitude of past events. In this study, we hypothesize that the morphometric characteristics of avalanche paths and their forest cover could have significant impacts on the length and reliability of tree-ring reconstructions. In order to test this hypothesis, we selected four adjacent, albeit differently structured, avalanche paths from the Queyras massif (French Alps), with the aim to compare their potential for a continuous reconstruction of past avalanche activity. On the most active avalanche paths characterized by high-altitude release areas (covered only by shrubby vegetation), tree-ring reconstructions do not exceed one century in length, with recurrence intervals of high magnitude events >25 years. By contrast, on forested couloirs where lower slopes and forest coverage up to the release areas limits the intensity of events, the frequency of reconstructed snow avalanches is 2.5 times higher, the reconstructions span longer periods and the convergence rate with historical archives attest to the reliability of the dendrogeomorphic approach. These results suggest that a careful selection of couloirs is essential and that priority should be given to forested sites as (i) they allow for exhaustive and (ii) reliable reconstructions over (iii) long periods of time.

Warm summers and moderate winter precipitation boost Rhododendron ferrugineum L. growth in the Taillefer massif (French Alps).

Rhododendron ferrugineum L. is a widespread dwarf shrub species growing in high-elevation, alpine environments of the Western European Alps. For this reason, analysis of its growth rings offers unique opportunities to push current dendrochronological networks into extreme environments and way beyond the treeline. Given that different species of the same genus have been successfully used in tree-ring investigations, notably in the Himalayas where Rhododendron spp. has proven to be a reliable climate proxy, this study aims at (i) evaluating the dendroclimatological potential of R. ferrugineum and at (ii) determining the major limiting climate factor driving its growth. To this end, 154 cross-sections from 36 R. ferrugineum individuals have been sampled above local treelines and at elevations from 1800 to 2100masl on northwest-facing slopes of the Taillefer massif (French Alps). We illustrate a 195-year-long standard chronology based on growth-ring records from 24 R. ferrugineum individuals, and document that the series is well-replicated for almost one century (1920-2015) with an Expressed Population Signal (EPS) >0.85. Analyses using partial and moving 3-months correlation functions further highlight that growth of R. ferrugineum is governed by temperatures during the growing season (May-July), with increasingly higher air temperatures favoring wider rings, a phenomenon which is well known from dwarf shrubs growing in circum-arctic tundra ecosystems. Similarly, the negative effect of January-February precipitation on radial growth of R. ferrugineum, already observed in the Alps on juniper shrubs, is interpreted as a result of shortened growing seasons following snowy winters. We conclude that the strong and unequivocal signals recorded in the fairly long R. ferrugineum chronologies can indeed be used for climate-growth studies as well as for the reconstruction of climatic fluctuations in Alpine regions beyond the upper limits of present-day forests.

Once versus twice daily enoxaparin for the initial treatment of acute venous thromboembolism.

Essentials In venous thromboembolism (VTE), it is uncertain if enoxaparin should be given twice or once daily. We compared the 15- and 30-day outcomes in VTE patients on enoxaparin twice vs. once daily. Patients on enoxaparin once daily had fewer major bleeds and deaths than those on twice daily. The rate of VTE recurrences was similar in both subgroups. SUMMARY: Background In patients with acute venous thromboembolism (VTE), it is uncertain whether enoxaparin should be administered twice or once daily. Methods We used the RIETE Registry data to compare the 15- and 30-day rates of VTE recurrence, major bleeding and death between patients receiving enoxaparin twice daily and those receiving it once daily. We used propensity score matching to adjust for confounding variables. Results The study included 4730 patients: 3786 (80%) received enoxaparin twice daily and 944 once daily. During the first 15 days, patients on enoxaparin once daily had a trend towards more VTE recurrences (odds ratio [OR], 1.79; 95% confidence interval [CI], 0.55-5.88), fewer major bleeds (OR, 0.42; 95% CI, 0.17-1.08) and fewer deaths (OR, 0.32; 95% CI, 0.13-0.78) than those on enoxaparin twice daily. At day 30, patients on enoxaparin once daily had more VTE recurrences (OR, 2.5; 95% CI, 1.03-5.88), fewer major bleeds (OR, 0.40; 95% CI, 0.17-0.94) and fewer deaths (OR, 0.58; 95% CI, 0.33-1.00). On propensity analysis, patients on enoxaparin once daily had fewer major bleeds at 15 (hazard ratio [HR], 0.30; 95% CI, 0.10-0.88) and at 30 days (HR, 0.16; 95% CI, 0.04-0.68) and also fewer deaths at 15 (HR, 0.37; 95% CI, 0.14-0.99) and at 30 days (HR, 0.19; 95% CI, 0.07-0.54) than those on enoxaparin twice daily. Conclusions Our findings confirm that enoxaparin prescribed once daily results in fewer major bleeds than enoxaparin twice daily, as suggested in a meta-analysis of controlled clinical trials.

Beta-blocker therapy and prognosis of heart failure patients with new-onset diabetes mellitus.

BACKGROUND: The influence of beta-blocker therapy (bisoprolol or carvedilol) (bB) on the prognosis of heart failure (HF) patients with diabetes mellitus (DM) is uncertain. AIMS: To assess the effect of bB on the prognosis of HF patients with new-onset DM treated with a contemporary medical regime. METHODS: Prospective study of 5314 HF patients with previously unknown DM. Mean age was 71.8±7.9 years, 53.0% were women, and 50.2% had HF with preserved ejection fraction (HFpEF). During a median follow-up of 56.9±18.2 months, 68.9% of the patients died, 88.6% were hospitalised for HF, and 1519 (27.3%) developed DM (62.3% of them received bB, 947 patients). We propensity-matched 572 HF patients with DM on bB, with 572 HF patients with DM non-treated with bB. RESULTS: Beta-blocker therapy was associated with a decreased hazard risk (HR) of all-cause death [HR: 0.68, CI 95% (0.61-0.75)], mainly because of a reduced risk of death from cardiovascular causes [HR: 0.70 (0.64-0.77)] (p<0.001). Similarly, bB was associated with a decreased HR of hospitalisation [HR: 0.82 (0.72-0.92)] (p<0.001). Nevertheless, the 30-day re-admission rate and the number of visits were not significantly associated with bB. These relationships of bB with prognosis were maintained, independently of the gender, the type of HF (HFpEF ot HFdEF), the comorbidities and the medication used (p<0.01). CONCLUSION: Therapy with bB, bisoprolol or carvedilol, is associated with a reduced mortality and morbidity of HF patients with new-onset DM, not only in men but also in women, as well as in patients with HFpEF or HFdEF.

Earliest known use of marine resources by Neanderthals.

Numerous studies along the northern Mediterranean borderland have documented the use of shellfish by Neanderthals but none of these finds are prior to Marine Isotopic Stage 3 (MIS 3). In this paper we present evidence that gathering and consumption of mollusks can now be traced back to the lowest level of the archaeological sequence at Bajondillo Cave (Málaga, Spain), dated during the MIS 6. The paper describes the taxonomical and taphonomical features of the mollusk assemblages from this level Bj(19) and briefly touches upon those retrieved in levels Bj(18) (MIS 5) and Bj(17) (MIS 4), evidencing a continuity of the shellfishing activity that reaches to MIS 3. This evidence is substantiated on 29 datings through radiocarbon, thermoluminescence and U series methods. Obtained dates and paleoenvironmental records from the cave include isotopic, pollen, lithostratigraphic and sedimentological analyses and they are fully coherent with paleoclimate conditions expected for the different stages. We conclude that described use of shellfish resources by Neanderthals (H. neanderthalensis) in Southern Spain started ∼150 ka and were almost contemporaneous to Pinnacle Point (South Africa), when shellfishing is first documented in archaic modern humans.

The Posidonia oceanica marine sedimentary record: A Holocene archive of heavy metal pollution.

The study of a Posidonia oceanica mat (a peat-like marine sediment) core has provided a record of changes in heavy metal abundances (Fe, Mn, Ni, Cr, Cu, Pb, Cd, Zn, As and Al) since the Mid-Holocene (last 4470yr) in Portlligat Bay (NW Mediterranean). Metal contents were determined in P. oceanica. Both, the concentration records and the results of principal components analysis showed that metal pollution in the studied bay started ca. 2800yr BP and steadily increased until present. The increase in Fe, Cu, Pb, Cd, Zn and As concentrations since ca. 2800yr BP and in particular during Greek (ca. 2680-2465cal BP) and Roman (ca. 2150-1740cal BP) times shows an early anthropogenic pollution rise in the bay, which might be associated with large- and short-scale cultural and technological development. In the last ca. 1000yr the concentrations of heavy metals, mainly derived from anthropogenic activities, have significantly increased (e.g. from ~15 to 47µg g(-1) for Pb, ~23 to 95µg g(-1) for Zn and ~8 to 228µg g(-1) for As). Our study demonstrates for the first time the uniqueness of P. oceanica meadows as long-term archives of abundances, patterns, and trends of heavy metals during the Late Holocene in Mediterranean coastal ecosystems.

Biomarkers in a peat deposit in Northern Spain (Huelga de Bayas, Asturias) as proxy for climate variation.

Peatlands are peculiar ecosystems in which well-adapted communities grow and develop, recording the variation in climate and hydrological conditions inland. In addition necromass is well preserved and therefore peatlands can be used as palaeo-archives for environmental variation. In this work a peat core of depth 60 cm dated at the bottom of the peat deposit as ca. 250cal AD from Huelga de Bayas (Asturias, Northern Spain) was studied to a resolution of 2-4 cm to investigate the evolution of the environmental conditions in the area. Samples were extracted with a dichloromethane/methanol ratio of 3:1 and studied by means of gas chromatography (GC) and mass spectrometry (GC-MS) in order to identify possible biomarkers of climatic variation during the period of peat formation. Lipid biomarker study allows the identification of periods in which Sphagnum or higher plants preferentially contributed to the peat profile. The absolute dating of the profile combined with the n-alkane record displayed five episodes of wetter conditions around ca. 250 cal AD (Roman Warm Period), 1080 and 1270 cal AD (Medieval Warm Period), 1460 cal AD (Little Ice Age) and 1920 cal AD (Recent warming), which are consistent with climate evolution in the region. Pentacyclic triterpenoids with hopane skeleton derived from microorganisms and with oleanane skeleton derived from higher plants were identified. The presence of their ketone and acetyl-derivatives, along with the presence of unstable hopane configurations indicates a low maturity of the peat profile. A tendency for the functionalised triterpenoids to decrease with depth was observed in the profile.

HSP90 and checkpoint-dependent lengthening of the G2 phase observed in plant cells under hypoxia and cold.

Proliferating cells of Allium cepa L. roots became adapted to hypoxia (5% oxygen) and cold (10 degrees C) by acquiring new steady-state kinetics of growth. The cell cycle time increased from the 17.6 h in control meristems up to 29.7 and 69.0 h under hypoxia and cold conditions, respectively. Acclimation of the proliferating cells was stress specific. No acclimation took place after 24 h of heat treatment (40 degrees C). Under cold treatment, all cycle phases enlarged uniformly. However, under hypoxia, while the G(1) and S cycle phases roughly doubled in their timing, the expected checkpoint-dependent lengthening of G(2) did not take place. This failure in lengthening G(2) in response to hypoxia correlated with a failure in the overinduction of a single peptide with a molecular mass of about 134 kDa which is among those recognised by an HSP90 antibody. Moreover, the presence of this large peptide of the HSP90 family proved to be a marker for cell proliferation. It was always absent from the contiguous differentiated cells of the root. Lastly, the mitochondrial chaperonin recognized by an HSP60 antibody in these roots not involved in photosynthesis was always higher in the proliferating than in the nonproliferating cells.

G2 checkpoint targets late replicating DNA.

In the multinucleate cells induced in Allium cepa L. meristems, the nuclei surrounded by the largest cytoplasm environment complete replication earlier (advanced nuclei), but have a longer G2, than the others (delayed nuclei). Thus, all nuclei break down the nuclear envelope and start metaphase simultaneously. The present report shows that this synchronization relies on a checkpoint mechanism. When completion of replication was prevented in the delayed nuclei (due to in vivo 5-aminouracil feeding initiated when the advanced nuclei were already in G2), the metaphase was also further delayed in the advanced ones. In turn, some of the delayed nuclei overrode the G2 checkpoint (adaptation) and entered into mitosis with broken chromatids (Del Campo et al., 1997). Anoxic UVA (313 nm) irradiation apparently prevents the binding of regulatory proteins to Br-DNA. The present report shows that late replicating sequences are the targets of the checkpoint signal produced by the still replicating nuclei. This signal delays metaphase in the advanced nuclei, whose DNA is already fully replicated. Thus, when the already replicated sequences of late replicating DNA was modified in the advanced nuclei by bromosubstitution followed by anoxic UVA irradiation, they entered into mitosis without any delay, ignoring the inhibitory signals produced by the still replicating nuclei.

Effect of caffeine on in vivo processing of alkylated bases in proliferating plant cells.

DNA damage was induced by either 2 mM ethylmethanesulfonate or 1 Gy of gamma-irradiation in Allium cepa L. root meristems. The percentage of DNA that migrated towards the anode during microelectrophoresis after alkali denaturation (pH approximately 13.5) of the isolated nuclei (comet assay) reflects the amount of single strand breaks present in them. There was some DNA migration (12.8+/-2.4%) in untreated roots. This percentage doubled at the end of 1.5 h treatment with the mono-functional alkylating agent 2 mM ethylmethanesulfonate, and trebled after a single exposure to 1 Gy of gamma-rays. A proportion of the DNA migration caused by these two treatments was reversed (repaired) by a 2 h long period of in vivo recovery. However, when 5 mM caffeine was applied after removal of the alkylating agent, the amount of DNA migrating to the comet tail over the same 2 h period was almost double that at the onset of recovery. In both control and irradiated nuclei, caffeine also increased the initial level of DNA migration in the comet assay, but to a lesser extent. These results indicate that caffeine increases the DNA damage that accumulates during the processing of alkylated bases and, to a lesser extent, of the DNA bases damaged by gamma-irradiation. Thus, the potentiation effect of caffeine on induced chromosomal damage may not just be due to caffeine-induced cancellation of the G2 checkpoint, but also to a direct effect this methylxantine has on the processing of DNA damage.

Human syndromes with genomic instability and multiprotein machines that repair DNA double-strand breaks.

The present report deals with the functional relationships among protein complexes which, when mutated, are responsible for four human syndromes displaying cancer proneness, and whose cells are deficient in DNA double-strand break (DSB) repair. In some of them, the cells are also unable to activate the proper checkpoint, while in the others an unduly override of the checkpoint-induced arrest occurs. As a consequence, all these patients display genome instability. In ataxia-telangiectasia, the mutated protein (ATM) is a kinase, which acts as a transducer of DNA damage signalling. The defective protein in the ataxia-telangiectasia-like disorder is a DNase (the Mre11 nuclease) that in vivo produces single-strand tails at both sides of DSBs. Mre11 is always present with the Rad50 ATPase in a protein machine: the nuclease complex. In mammals, this complex also contains nibrin, the protein mutated in the Nijmegen syndrome. Nibrin confers new abilities to the nuclease complex, and can also bind to BRCA1 (one of the two proteins mutated in familial breast cancer). BRCA1 has a central motif that binds with high affinity to cruciform DNA, a structure present in places where the DNA loops are anchored to the chromosomal axis or scaffold. The BRCA1 x cruciform DNA complex should be released to allow the nuclease complex to work in DNA recombinational repair of DSBs. BRCA1 also acts as a scaffold for the assembly of ATPases such as Rad51, responsible for the somatic homologous recombination. Loss of the BRCA1 gene prevents cell survival after exposure to cross-linkers. The BRCA1-RING domain is an E3-ubiquitin ligase. It can mono-ubiquitinate the FANCD2 protein, mutated in one of the Fanconi anemia complementation groups, to regulate it. Finally, during DNA replication, the nuclease complex and its activating ATM kinase are integrated in the BRCA1-associated surveillance complex (BASC) that contains, among others, enzymes required for mismatch excision repair. In short, the proteins missing in these syndromes have in common their BRCA1-mediated assembly into multimeric machines responsible for the surveillance of DNA replication, DSB recombinational repair, and the removal of DNA cross-links.

[Possible prognostic value of arterial hypertension in postmenopausal women with breast cancer in complete clinical remission. Pilot study]. / Posible valor pronóstico de la hipertensión arterial en mujeres postmenopáusicas con cáncer de mama. Estudio piloto.

BACKGROUND: The objective of this work was to determine the blood pressure of postmenopausal women with breast cancer in complete clinical remission of long duration. MATERIAL AND METHODS: It in a pilot study of case and controls, in which we measure the Blood Pressure (BP) of 83 postmenopausal women, with breast cancer histologically confirmed, in complete clinical remission of long duration, recruited by consecutive sampling, to compare it with that of 70 normal postmenopausal women of the same age used as controls. They ara calculated the body mass index (BMI), the corporal surface, the confidence intervals (CI) of the means, the correlation between the BMI and the BP in both groups (breast cancer patients and normal control) and between the free disease interval and the systolic and diastolic blood pressures. RESULTS: The mean of the systolic BP in 93 breast cancer patients in complete clinical remission was 163 mm Hg (95% CI 155-171) and in 70 normal controls was 134 mm Hg (95% CI 129-139). The difference between both groups in statistically significant (p < 0.001). The mean of the diastolic BP in the breast cancer patient in complete remission it was 98 mm Hg (94-104) and in the normal controls was 78 mm Hg (74-82). The difference between both groups was statistically significant (p < 0.001). CONCLUSIONS: This arterial hypertension, independent of the BMI and from the duration of the free disease interval, is associated with a long duration of the complete remission in postmenopausal breast cancer patients and consequently with a good prognostic of this disease.

Ataxia telangiectasia: G2 checkpoint and chromosomal damage in proliferating lymphocytes.

There is a checkpoint pathway in eukaryotic cells that depends on ATM (ataxia telangiectasia mutated) kinase which activates the processes leading to the repair of DNA damage and also lengthens the G(2) stage of the cell cycle. In cells from ataxia telangiectasia patients, due to their lack of active ATM kinase, an increase in chromosomal aberrations and a failure to induce G(2) lengthening could be expected. However, the basal G(2) timing in ataxia telangiectasia cells was longer than in controls and was further extended after X-ray irradiation (0.4 Gy), although to a lesser extent than in controls. Moreover, in control cells caffeine shortened G(2) and increased chromosomal damage 7-fold, while in ataxia telangiectasia cells caffeine only trebled aberration yield without shortening G(2). As caffeine is an inhibitor of ATM kinase, these results suggest the existence of some redundant ATM-independent checkpoint in G(2) of ataxia telangiectasia cells. The differential response to caffeine of ataxia telangiectasia and control lymphocytes may be explained by the presence of two different subpathways in the G(2) checkpoint: one regulating the processing and repair of damaged DNA and the other controlling G(2) timing. While in controls both subpathways may be mediated by ATM kinase, in ataxia telangiectasia cells caffeine-sensitive ATR kinase and the caffeine-insensitive DNA-PK kinases might be responsible for DNA repair and the G(2) delay subpathways, respectively. Confirmation of this model in ataxia telangiectasia cells with another cell type in which both subpathways are mediated by DNA-PK should define whether a metylxanthine such as caffeine may also have an additional direct inhibitory effect on DNA repair.

Enhancement of splenic-macrophage Fcgamma receptor expression by treatment with estrogens.

Splenic-macrophage Fcgamma receptors (FcgammaRs) participate in the pathophysiologies of immune-complex diseases and in host defense against infection. Modulation of macrophage FcgammaR expression is an immuno-therapeutic target. Glucocorticoids, sex steroids, and dopaminergic drugs modulate macrophage FcgammaR expression. Previous data indicate that estradiol increases macrophage FcgammaR expression. Nevertheless, the effects of clinically used estrogens upon macrophage FcgammaR expression are unknown. We assessed the effects of treatment with commonly used estrogens on the expression of macrophage FcgammaRs using a guinea pig experimental model. Six estrogens have been studied: ethynylestradiol (Et), mestranol (M), chlortianisene (Ct), promestriene, 17-epiestriol, and 17beta-estradiol. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic-macrophage FcgammaR cell surface expression. Estrogens enhance the clearance of IgG-sensitized erythrocytes by increasing splenic-macrophage FcgammaR expression. Et, M, and Ct were more effective than the other estrogens. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that estrogens increase the cell surface expression of FcgammaR1 and -2 more than that of FcgammaR2. These data indicate that treatment with commonly used estrogens enhances the clearance of IgG-sensitized cells by improving splenic-macrophage FcgammaR expression.

La proteína p53 y el cáncer de mama. Revisión crítica / The p53 protein and breast cancer

Es una revisión crítica de las bases biológicas de la proteína p53 en la apoptosis, su importancia en la carcinogénesis experimental y humana y los procedimientos técnicos de laboratorio que pueden emplearse para su determinación en los enfermos de cáncer. La hiperexpresión de p53 por la presencia de una mutación origina una acumulación excesiva en los tejidos, relacionada con la vida media de la proteína mutada que es aproximadamente unas 60 veces más larga que la proteína natural. Los clínicos hablan de positividad de la p53 como la presencia de p53 mutada. Quizás, uno de los aspectos mejor estudiados de esta proteína es su comportamiento en el cáncer de mama. Actualmente puede ser considerada un factor pronóstico del cáncer de mama y es recomendable incluirla entre las determinaciones inmunohistoquímicas a realizar en la pieza por el anatomopatólogo clínico. Los procedimientos empleados para investigar la p53 son:a) análisis molecular; b) análisis inmunohistoquímico, y c) análisis serológico. El último es un nuevo y prometedor procedimiento serológico para detectar la p53 mutada en sangre periférica que abre importantes expectativas. Es útil para identificar los casos de mal pronóstico entre el grupo favorable con N0 (ganglios axilares negativos) (AU)

Posible valor pronóstico de la hipertensión arterial en mujeres postmenopáusicas con cáncer de mama. Estudio piloto / Possible prognostic value of arterial hypertension in postmenopausal women with breast cancer in complete clinical remission. Pilot study

Fundamento: El objetivo de este trabajo fue determinar la presión arterial (PA) en mujeres postmenopáusicas con cáncer de mama en remisión clínica completa de larga duración. Material y métodos: Se trata de un estudio piloto, de casos y controles, en los cuales se midieron la presión arterial de 83 mujeres postmenopáusicas, con cáncer de mama histológicamente confirmado en situación de remisión clínica completa de larga duración comparándolo con un grupo control de 70 mujeres sanas postmenopáusicas, de la misma edad. Se calculó el índice de masa corporal (BMI), la superficie corporal, el intervalo de confianza de la media, la correlación entre el BMI y la PA, en ambos grupos (cáncer de mama/mujeres sanas) y las presiones sistólicas y diastólicas. Resultados: La media de la presión sistólica en las 83 mujeres con cáncer de mama fue de 163 mm de Hg (95 por ciento CI 155-171) y en los 70 controles normales fue de 134 mm de Hg (95 por ciento CI 129-139). La diferencia entre ambos grupos fue estadísticamente significativa (p<0,001). La media de la presión diastólica en las mujeres con cáncer fue de 98 mm de Hg (94-104) y en los controles normales fue de 78 mm de Hg (74-82). La diferencia entre ambos grupos fue estadísticamente significativa (p<0,001). Conclusiones: La hipertensión arterial, independientemente del BMI y de la duración del intervalo libre de enfermedad, está asociado con una mayor duración de la remisión clínica completa en las mujeres postmenopáusicas con cáncer de mama y consecuentemente con un mejor pronóstico de su enfermedad cancerosa (AU)

Fanconi anemia lymphocytes: effect of DL-alpha-tocopherol (Vitamin E) on chromatid breaks and on G2 repair efficiency.

The high frequency of chromosomal breaks in Fanconi anemia (FA) lymphocytes has been related to the increased oxidative damage shown by these cells. The effect of 100 microM DL-alpha-tocopherol (Vitamin E) on the level of chromosomal damage in mitosis was studied in lymphocytes from five FA patients and from age matched controls, both under basal conditions and when G2 repair was prevented by 2.5 mM caffeine (G2 unrepaired damage). In addition, the effect of this antioxidant on G2 duration and the efficiency of G2 repair was also evaluated in the sample. alpha-Tocopherol (AT) decreased the frequency of chromosomal damage (under basal and inhibited G2 repair conditions) and the duration of G2 in FA cells. This antioxidant protective effect, expressed as the decrease in chromatid breaks, was greater in FA cells (50.8%) than in controls (25%). The efficiency of the G2 repair process (G2 R rate) defined as the ratio between the percentage of chromatid breaks repaired in G2 and the duration of this cell cycle phase was lesser in FA cells (10.6) than in controls (22.6). AT treatment slightly increased this G2 R rate, both in FA cells and controls. These results suggest that an increased oxidative damage and a lower G2 repair rate may be simultaneously involved in the high frequency of chromatid damage detected in FA cells.