Contributions to the Eocene palaeontology and stratigraphy of Beira Alta, Portugal II - New Late Eocene mammalian remnants from Coja (Portugal) and the presence of Palaeotherium magnum Cuvier

The presence of Palaeotherium magnum in the fauna from Coja is recorded. It is well in agreement with the earlier reporting to the Montmartre level from the Ludian stage. Field data as well as compatibility with the remaining taxa and the identical fossilization of all the specimens indicate that all the vertebrate fossils come from the same horizon in the lithostratigraphic unit "Arcoses de Côja".

Percutaneous mitral valvotomy in patients eighteen years old and younger. Immediate and late results

OBJECTIVE - To analyze immediate and late results of percutaneous mitral valvotomy (PMV) in patients <= 18 year. METHODS - Between August '87 and July '97, 48 procedures were performed on 40 patients. The mean age was 15.6 years; 68.7% were females four of whom were pregnant. RESULTS - Success was obtained in 91.7% of the procedures. Immediate complications were severe mitral regurgitation (6.3%) and cardiac tamponade (2.0%). Late follow-up was obtained in 88.8% of the patients (mean value=43.2±33.9 months). NYHA functional class (FC) I or II was observed in 96.2% of the patients and restenosis developed in five patients, at a mean follow-up of 29.7±11.9 months. Three patients presented with severe mitral insufficiency and underwent surgery. Two patients died. CONCLUSION - PMV represents a valid therapeutic option in young patients. In these patients, maybe because of subclinical rheumatic activity, restenosis may have a higher incidence and occur at an earlier stage than in others persons.

Unexpectedly late expression of intracellular CD3epsilon and TCR gammadelta proteins during adult thymus development.

During adult thymus development immature CD4(-)CD8(-) [double-negative (DN)] precursor cells pass through four phenotypically distinct stages defined by expression of CD44 and CD25: CD44(hi)CD25(-) (DN1), CD44(hi)CD25(+) (DN2), CD44(lo)CD25(+) (DN3) and CD44(lo)CD25(-) (DN4). Although it is well established that the TCR beta, gamma and delta genes are rearranged and expressed in association with the CD3 components in DN thymocytes, the precise timing of expression of the TCR and CD3 proteins has not been determined. In this report we have utilized a sensitive intracellular (ic) staining technique to analyze the expression of ic CD3epsilon, TCR beta and TCR gammadelta proteins in immature DN subsets. As expected from previous studies of TCR beta rearrangement and mRNA expression, icTCR beta(+) cells were first detected in the DN3 subset and their proportion increased thereafter. Surprisingly, however, both icCD3epsilon(+) and icTCR gammadelta(+) cells were detected at later stages of development than was predicted by molecular studies. In particular icCD3epsilon protein expression coincided with the transition from the DN2 to DN3 stage of development, whereas icTCR gammadelta protein expression was only detected in a minor subset of DN4 cells. The implications of these findings for alphabeta lineage divergence will be discussed.

Late outcome of spinal cord stimulation for unreconstructable and limb-threatening lower limb ischemia.

OBJECTIVES: To determine whether the initial benefits of spinal cord stimulation (SCS) treatment for critical limb ischemia (CLI) persist over years. DESIGN: Analysis of data prospectively collected for every CLI patient receiving permanent SCS. Follow-up range 12 to 98 months (mean 46+/-23, median 50 months). POPULATION: 87 patients (28% stage III, 72%stage IV) with unreconstructable CLI due (83%) or not (17%) to atherosclerosis and with an initial sitting/supine transcutaneous pO2 gradient >15 mmHg. METHODS: Assessment of actuarial patient survival (PS), limb salvage (LS) and amputation-free patient survival (AFPS). Analysis of the impact of 15 risk factors on long-term outcomes using the Fischer's exact test for categorical variables and the t test for continuous variables. RESULTS: Follow-up was complete for patient and limb survival. A single non-atherosclerotic patient died during follow-up. Among atherosclerotic patients PS decreased from 88% at 1y, to 76% at 3y, 64% at 5y and 57% at 7y. LS reached 84% at 1y, 78% at 2y, 75% at 3y and remained stable thereafter. Diabetes was found to affect LS (p<0.05) and heart disease to reduce PS (p<0.01). AFPS was reduced in heart patients (p<0.01), diabetics (p<0.05) and in patients with previous stroke (p<0.05). CONCLUSIONS: In CLI patients the beneficial effects of SCS persist far beyond the first year of treatment and major amputation becomes infrequent after the second year.

Accreted fragments of the Late Cretaceous Caribbean-Colombian Plateau in Ecuador

The eastern part of the Western Cordillera of Ecuador includes fragments of an Early Cretaceous ( approximate to 123 Ma) oceanic plateau accreted around 85-80 Ma (San Juan unit). West of this unit and in fault contact with it, another oceanic plateau sequence (Guaranda unit) is marked by the occurrence of picrites, ankaramites, basalts, dolerites and shallow level gabbros. A comparable unit is also exposed in northwestern coastal Ecuador (Pedernales unit). Picrites have LREE-depleted patterns, high epsilonNd(i) and very low Pb isotopic ratios, suggesting that they were derived from an extremely depleted source. In contrast, the ankaramites and Mg-rich basalts are LREE-enriched and have radiogenic Pb isotopic compositions similar to the Galapagos HIMU component; their epsilonNd(i) are slightly lower than those of the picrites. Basalts, dolerites and gabbros differ from the picrites and ankaramites by flat rare earth element (REE) patterns and lower epsilonNd; their Pb isotopic compositions are intermediate between those of the picrites and ankaramites. The ankaramites, Mg-rich basalts, and picrites differ from the lavas from the San Juan-Multitud Unit by higher Pb ratios and lower epsilonNd(i). The Ecuadorian and Gorgona 88-86 Ma picrites are geochemically similar. The Ecuadorian ankaramites and Mg-rich basalts share with the 92-86 Ma Mg-rich basalts of the Caribbean-Colombian Oceanic Plateau (CCOP) similar trace element and Nd and Pb isotopic chemistry. This suggests that the Pedernales and Guaranda units belong to the Late Cretaceous CCOR The geochemical diversity of the Guaranda and Pedernales rocks illustrates the heterogeneity of the CCOP plume source and suggests a multi-stage model for the emplacement of these rocks. Stratigraphic and geological relations strongly suggest that the Guaranda unit was accreted in the late Maastrichtian (approximate to 68-65 Ma). (C) 2002 Elsevier Science B.V. All rights reserved.

Interferon-gamma is required for the late but not early control of Leishmania amazonensis infection in C57Bl/6 mice

The critical role of interferon-gamma (IFN-g) in the resistance of C57Bl/6 mice to Leishmania major is widely established but its role in the relative resistance of these animals to L. amazonensis infection is still not clear. In this work we use C57Bl/6 mice congenitally deficient in the IFN-g gene (IFN-g KO) to address this issue. We found that IFN-g KO mice were as resistant as their wild-type (WT) counterparts at least during the first two months of infection. Afterwards, whereas WT mice maintained lesion growth under control, IFN-g KO mice developed devastating lesions. At day 97 of infection, their lesions were 9-fold larger than WT controls, concomitant with an increased parasite burden. At this stage, lesion-draining cells from IFN-g KO mice had impaired capacity to produce interleukin-12 (IL-12) and tumour necrosis factor-a in response to parasite antigens whereas IL-4 was slightly increased in comparison to infected WT mice. Together, these results show that IFN-g is not critical for the initial control of L. amazonensis infection in C57Bl/6 mice, but is essencial for the developmente of a protective Th1 type immune response in the later stages.

Late pulmonary metastases of renal cell carcinoma immediatelyafter post-transplantation immunosuppressive treatment: a case report

INTRODUCTION We report a case of pulmonary metastatic recurrence of renal adenocarcinoma soon after radical nephrectomy that was followed by renal transplant and immunosuppressive medication. Increased risk of metastatic recurrence of renal cell carcinoma should be considered in the immediate post-transplant period when immunosuppressive medication is administered, even if nephrectomy had been performed many years earlier. CASE PRESENTATION In 1986 the patient demonstrated renal insufficiency secondary to mesangial glomerulonephritis. In 1992 he underwent left side radical nephrectomy with histopathological diagnosis of clear cell adenocarcinoma. Mesangial glomerulonephritis in the remaining right kidney progressed to end-stage renal failure. In October 2000 he received a kidney transplant from a cadaver and commenced immunosuppressive medication. Two months later, several nodules were found in his lungs, which were identified as metastases from the primary renal tumor that had been removed with the diseased kidney 8 years earlier. CONCLUSION Recurrence of renal cell carcinoma metastases points to tumor dormancy and reflects a misbalance between effective tumor immune surveillance and immune escape. This case demonstrates that a state of tumor dormancy can be interrupted soon after administration of immunosuppressant medication.

Correlation of meta 1 expression with culture stage, cell morphology and infectivity in Leishmania (Leishmania) amazonensis promastigotes

The parasitic protozoan Leishmania (Leishmania) amazonensis alternates between mammalian and insect hosts. In the insect host, the parasites proliferate as procyclic promastigotes andthen differentiate into metacyclic infective forms. The meta 1 gene is preferentially expressed during metacyclogenesis. Meta 1 expression profile determination along parasite growth curves revealed that the meta 1 mRNA level peaked at the early stationary phase then decreased to an intermediate level. No correlation was observed between meta 1 expression and infectivity. Conversely, infectivity correlated with the increase of apoptotic cells in the late stationary phase.

The Life Course Determinants of Vulnerability in Late Careers

Late career is often seen as a more vulnerable life-stage in the labour market, in which workers may experience a deterioration in job quality. Using a life course perspective and longitudinal data, this article analyses the vulnerability associated with late career by focusing on four occupational dimensions: working-time, career continuity, retirement timing and income change. The research is carried out using data from Switzerland, a country where the age profile of the labour force is an increasing issue. The paper also adopts a cumulative disadvantage perspective to examine the impact of previous work and family life experiences on work life vulnerability at older age. Our data come from the Survey of Health, Ageing and Retirement in Europe (SHARELIFE). The paper uses cluster analysis, sequence analysis and ordered logistic regression. Results show that women with previous family responsibilities resulting in long-term unemployment or caring, often with health complications, are more likely to be vulnerable to deterioration in job quality in late career. This suggests that experiences in the last period of the working life may be just as gendered as earlier periods.

Bitumens in the late Variscan hydrothermal vein-type uranium deposit of Pribram, Czech Republic: Sources, radiation-induced alteration, and relation to mineralization

The late Variscan (275-278 Ma) Pribram uranium deposit is one of the largest known accumulations of uraniferous bitumens in hydrothermal veins. The deposit extends along the northwestern boundary of the Central Bohemian pluton (345-335 Ma) with low-grade metamorphosed Late Proterozoic and unmetamorphosed Cambrian rocks. From a net uranium production of 41,742 metric tons (t), more than 6,000 t were extracted from bitumen-uraninite ores during 43 years of exploration and mining. Three morphological varieties of solid bitumen are recognized: globular, asphaltlike, and cokelike. While the globular bitumen is uranium free, the other two types are uraniferous. The amount of bitumen in ore veins gradually decreases toward the contact with the plutonic body and increases with depth. Two types of bitumen microtextures are recognized using high-resolution transmission electron microscopy: amorphous and microporous, the former being less common in uraniferous samples. A lower Raman peak area ratio (1,360/1,575 cm(-1)) in mineralized bitumens (0.9) compared with uranium-free samples (2.0) indicates a lower degree of microtextural organization in the latter The H/C and O/C atomic ratios in uranium-free bitumens (0.9-1.1 and 0.09, respectively) are higher than those in mineralized samples (H/C = 0.3-0.8, O/C = 0.03-0.09). The chloroform extractable matter yield is Very low in uranium-free bitumens (0.30-0.35% of the total organic carbon,TOC) and decreases with uranium content increase. The extracted solid uraniferous bitumen infrared spectra show depletion in aliphatic CH2 and CH3 groups compared to uranium-free samples. The concentration of oxygen-bearing functional groups relative to aromatic bonds in the IR spectra of uranium-free and mineralized bitumen, however, do not differ significantly. C-13 NMR confirmed than the aromaticity of a uraniferous sample is higher (F-ar = 0.61) than in the uranium-free bitumen (F-ar = 0.51). Pyrolysates from uraniferous and nonuraniferous bitumens do not differ significantly, being predominantly cresol, alkylphenols, alkylbenzenes, and alkylnaphthalenes. The liquid pyrolysate yield decreases significantly with increasing uranium content. The delta(13)C Values of bulk uranium-free bitumens and low-grade uraniferous, asphaltlike bitumens range from -43.6 to 52.3 per mil. High-grade, cokelike, uraniferous bitumens are more C-13 depleted (54.5 to -58.4 parts per thousand). In contrast to the very light isotopic ratios of the high-grade uraniferous cokelike bitumen bulk carbon, the individual n-alkanes and isoprenoids (pristane and phytane) extracted from the same sample are significantly C-13 enriched. The isotopic composition of the C13-24 n-alkanes extracted from the high-grade uraniferous sample (delta(13)C = -28.0 to 32.6 parts per thousand) are heavier compared with the same compounds in a uranium-free sample (delta(13)C = 31.9 to 33.8 parts per thousand). It is proposed that the bitumen source was the isotopically light (delta(13)C = 35.8 to 30.2 parts per thousand) organic matter of the Upper Proterozoic host rocks that were pyrolyzed during intrusion of the Central Bohemian pluton. The C-13- depleted pyrolysates were mobilized from the innermost part of the contact-metamorphic aureole, accumulated in structural traps in less thermally influenced parts of the sedimentary complex and were later extracted by hydrothermal fluids. Bitumens at the Pribram deposit are younger than the main part of the uranium mineralization and were formed through water-washing and radiation-induced polymerization of both the gaseous and liquid pyrolysates. Direct evidence for pyrolysate reduction of uranium in the hydrothermal system is difficult to obtain as the chemical composition of the original organic fluid phase was modified during water-washing and radiolytic alteration. However, indirect evidence-e.g., higher O/C atomic ratios in uranium-free bitumens (0.1) relative to the Upper Proterozoic source rocks (0.02-0.05), isotopically very light carbon in associated whewellite (delta(13)C = 31.7 to -28.4 parts per thousand), and the striking absence of bitumens in the pre-uranium, hematite stage of the mineralization-indicates that oxidation of organic fluids may have contributed to lowering of aO(2) and uraninite precipitation.

Late Onset Cystoid Macular Oedema Following Surgery for Radiation Induced Cataract in Patient With Retinoblastoma

Purpose: Cystoid macular oedema (CMO) is a very rare condition following cataract surgery in paediatric population. Nevertheless, we report a case series of patients with radiation induced cataract after retinoblastoma (Rb) treatment that underwent cataract surgery and developed subsequently late onset CMO. Methods: Between January 1984 and December 2009, 25 consecutive eyes (25 patients) with Rb presented with radiation induced cataract surgery at the Jules Gonin Eye Hospital. Sixteen eyes (16 patients) had prior radiation induced retinopathy and maculopathy (IRM). Out of these, 3 eyes (3 patients) developed CMO after cataract surgery. Results: One eye had Rb stage B, and 2 eyes had stage D International classification. All of them developed IRM following brachytherapy and/or external beam irradiation. Patients underwent phako-aspiration and in bag intraocular lens implantation after IRM had resolved. Mean age at cataract surgery was 10.7 ± 2.8 (SEM) (range 5-14) years old. Mean time between resolution of IRM and cataract surgery was 76.0 ± 27.2 (SEM) (range 24-116) months. Mean time of onset CMO after cataract surgery was 81.0 ± 34.4 (SEM) (range 13-124) months. There was no other underlying vascular or tractional factor for CMO development. All of them were treated with a combination of oral carbonic anhydrase inhibitor, topical steroid and topical non-steroid. Mean macular thickness pre-, during-, and post CMO were 134.0 ± 10.3, 298.0 ± 37.1, and 154.0 ± 4.0 (SEM) µm, respectively. Mean best corrected visual acuity pre-, during-, and post CMO were 0.31 ± 0.19, 0.46 ± 0.12, and 0.34 ± 0.18 (SEM) LogMAR, respectively. Mean time for CMO reabsorption was 17.0 ± 9.8 (SEM) months. Conclusions: To the best of our knowledge, CMO following paediatric cataract surgery is a very uncommon condition. Moreover, late onset CMO after phako-aspiration for radiation induced cataract in Rb patients has never been described. It is a rare complication but can be treated successfully.

Should possible recurrence of disease contraindicate liver transplantation in patients with end-stage alveolar echinococcosis? A 20-year follow-up study.

Liver transplantation (LT) is currently contraindicated in patients with residual or metastatic alveolar echinococcosis (AE) lesions. We evaluated the long-term course of such patients who underwent LT and were subsequently treated with benzimidazoles. Clinical, imaging, serological, and therapeutic data were collected from 5 patients with residual/recurrent AE lesions who survived for more than 15 years. Since 2004, [(18) F]-2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) images were available, and the levels of serum antibodies (Abs) against Echinococcus multilocularis-recombinant antigens were evaluated. Median survival time after LT was 21 years. These patients were from a prospective cohort of 23 patients with AE who underwent LT: 5 of 8 patients with residual/recurrent AE and 4 of 9 patients without residual/recurrent AE were alive in September 2009. High doses of immunosuppressive drugs, the late introduction of therapy with benzimidazoles, its withdrawal due to side effects, and nonadherence to this therapy adversely affected the prognosis. Anti-Em2(plus) and anti-rEm18 Ab levels and standard FDG-PET enabled the efficacy of therapy on the growth of EA lesions to be assessed. However, meaningful variations in Ab levels were observed below diagnostic cutoff values; and in monitoring AE lesions, images of FDG uptake taken 3 hours after its injection were more sensitive than images obtained 1 hour after its injection. In conclusion, benzimidazoles can control residual/recurrent AE lesions after LT. Using anti-rEm18 or anti-Em2(plus) Ab levels and the delayed acquisition of FDG-PET images can improve the functional assessment of disease activity. The potential recurrence of disease, especially in patients with residual or metastatic AE lesions, should not be regarded as a contraindication to LT when AE is considered to be lethal in the short term.

Late Pan-African magmatism in the Himalaya: new geochronological and geochemical data from the Ordovician Tso Morari metagranites (Ladakh, NW India)

Two granitic plutons, the Tso Morari gneiss and the Rupshu metagranite, crop out in the Tso Morari area. The Polokongka La granite, classically interpreted as a young intrusion in the Tso Morari gneiss, has been recognized as the undeformed facies of the latter. Conventional isotope dilution U-Pb zircon dating on single-grain and small multi-grain fractions yielded magmatic ages of 479 +/- 2 Ma for the Tso Morari gneiss and the Polokongka La granite, and 482.5 +/- 1 Ma for the Rupshu granite. There is a great difference in zircon morphology between the Tso Morari gneiss (peraluminous type) and the Rupshu granite (alkaline type). This difference is confirmed by whole-rock chemistry. The Tso Morari gneiss is a typical deformed S-type granite, resulting from crustal anatexis. On the other hand, the Rupshu granite is an essentially metaluminous alkali-calcic intrusion derived from a different source material. Data compilation from other Himalayan Cambro-Ordovician granites reveals huge and widespread magmatic activity all along and beyond the northern Indian plate between 570 and 450 Ma, with a peak at 500-480 Ma. A major, continental-scale tectonic event is required to generate such a large magmatic belt; it has been tentatively compared to the Variscan post-orogenic extensional regime of Western Europe, as a late evolution stage of a Pan-African orogenic event.

Late Jurassic continental flood basalt doleritic dykes in northwestern Cuba: remnants of the Gulf of Mexico opening

Accreted terranes, comprising a wide variety of Late Jurassic and Early Cretaceous igneous and sedimentary rocks are an important feature of Cuban geology. Their characterization is helpful for understanding Caribbean paleogeography. The Guaniguanico terrane (western Cuba) is formed by upper Jurassic platform sediments intruded by microgranular dolerite dykes. The geochemical characteristics of the dolerite whole rock samples and their minerals (augitic clinopyroxene, labradorite and andesine) are consistent with a tholeiitic affinity. Major and trace element concentrations as well as Nd, Sr and Pb isotopes show that these rocks also have a continental affinity. Sample chemistry indicates that these lavas are similar to a low Ti-P2O5 (LTi) variety of continental flood basalts (CFB) similar to the dolerites of Ferrar (Tasmania). They derived from mixing of a lithospheric mantle Source and an asthenopheric component similar to E-MORB with minor markers of crustal contamination and sediment assimilation. However, the small quantity of Cuban magmatic rocks, similarly to Tasmania, Antarctica and Siberia differs from other volumetrically important CFB occurrences Such as Parana and Deccan. These dolerites are dated as 165-150 Ma and were emplaced during the separation of the Yucatan block from South America. They could in fact be part of the Yucatan-South America margin through which the intrusive system was emplaced and which was later accreted to the Cretaceous arc of central Cuba and to the Palaeogene arc of eastern Cuba. These samples could therefore reflect the pre-rift stage between North and South America and the opening of the gulf of Mexico.

Concurrent or Sequential Adjuvant Hormonoradiotherapy after Conservative Surgery for Early-Stage Breast Cancer: Clinical Results of the CO-HO-RT Phase II Randomized Trial.

Purpose: Letrozole (LET) has recently been shown to be superior to tamoxifen for postmenopausal patients (pts). In addition, LET radiosensitizes breast cancer cells in vitro. We conducted a phase II randomized study to evaluate concurrent and sequential radiotherapy (RT)-LET in the adjuvant setting. We present here clinical results with a minimum follow-up of 24 months. Patients and Methods: Postmenopausal pts with early-stage breast cancer were randomized after conservative surgery to either: A) concurrent RT-LET (LET started 3 weeks before the first day of RT) or B) sequential RT-LET (LET started 3 weeks after the end of RT). Whole breast RT was delivered to a total dose of 50 Gy. A 10-16 Gy boost was allowed according to age and pathological prognostic factors. Pts were stratified by center, adjuvant chemotherapy, boost, and radiation-induced CD8 apoptosis (RILA). RILA was performed before RT as previously published (Ozsahin et al. Clin Cancer Res, 2005). An independent monitoring committee reviewed individual safety data. Skin toxicities were evaluated by two different clinicians at each medical visit (CTCAE v3.0). Lung CT-scan and functional pulmonary tests were performed regularly. DNA samples were screened for SNPs in candidate genes as recently published (Azria et al., Clin Cancer Res, 2008). Results: A total of 150 pts were randomized between 01/05 and 02/07. Median follow-up is 26 months (range, 3-40 months). No statistical differences were identified between the two arms in terms of mean age; initial TNM; median surgical bed volume; post surgical breast volume. Chemotherapy and RT boost were delivered in 19% and 38% of pts, respectively. Nodes received 50 Gy in 23% of patients without differences between both arms. During RT and within the first 6 weeks after RT, 10 patients (6.7%) presented grade 3 acute skin dermatitis during RT but no differences were observed between both arms (4 and 6 patients in arm A and B, respectively). At 26 month of follow-up, grade 2 and more radiation-induced subcutaneous fibrosis (RISCF) was present in 4 patients (3%) without any difference between arm A (n = 2) and B (n = 2), p=0.93. In both arms, all patients that presented a RICSF had a RILA lower than 16%. Sensitivity and specificity were 100% and 39%, respectively.No acute lung toxicities were observed and quality of life was good to excellent for all patients.SNPs analyses are still on-going (Pr Rosenstein, NY). Conclusion: Acute and early late grade 2 dermatitis were similar in both arms. The only factor that influenced RISCF was a low radiation-induced lymphocyte apoptosis yield. We confirmed prospectively the capacity of RILA for identifying hypersensitive patients to radiation. Indeed, patients with RILA superior to 16% did not present late effects to radiation and confirmed the first prospective trial we published in 2005 (Ozsahin et al., Clin Cancer Res).