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This article discusses the dichotomy between barbarity and civilization in 18th century Europe. The author comments on the writings of Spanish travelers in Europe at the time and describes the influence of the Enlightenment on European society, ethics, and aesthetics. The establishment of a national identity throughout Europe, according to these travel narratives, is also examined.

An introduction is presented for the following section of articles, which focus on civilization, emotions, and the civilizing process theory.

The recent World Health Organization classification recognizes different subtypes of acute myeloid leukemia (AML) according to the presence of several recurrent genetic abnormalities. Detection of these abnormalities and other molecular changes is of increasing interest because it contributes to a refined diagnosis and prognostic assessment in AML and enables monitoring of minimal residual disease. These genetic abnormalities can be detected using single RT-PCR, although the screening is still labor intensive and costly. We have developed a novel real-time RT-PCR assay to simultaneously detect 15 AML-associated rearrangements that is a simple and easily applicable method for use in clinical diagnostic laboratories. This method showed 100% specificity and sensitivity (95% confidence interval, 91% to 100% and 92% to 100%, respectively). The procedure was validated in a series of 105 patients with AML. The method confirmed all translocations detected using standard cytogenetics and fluorescence in situhybridization and some additional undetected rearrangements. Two patients demonstrated two molecular rearrangements simultaneously, with BCR-ABL1implicated in both, in addition to RUNX1-MECOMin one patient and PML-RARAin another. In conclusion, this novel real-time RT-PCR assay for simultaneous detection of multiple AML-associated fusion genes is a versatile and sensitive method for reliable screening of recurrent rearrangements in AML.

Renal artery embolization is a procedure that has been shown to be useful as a concomitant treatment for the resection of large renal tumors. Over the years, preoperative renal artery embolization concomitant with nephrectomy as a treatment option has proved to be useful in reducing morbi-mortality rates; however this procedure is not exempt from significant iatrogenia. Performing this technique in conjunction with nephrectomy in a single surgical act helps to maintain the advantages of this treatment, which in turn considerably reduces the associated morbi-mortality rates.

The most frequent KITmutations reported in core-binding factor acute myeloid leukemia are point mutations and insertions/deletions in exons 17 and 8. The vast majority of KITmutation detection procedures are time-consuming, costly, or with a high lower limit of detection. High-resolution melting (HRM) is a gene scanning method that combines simplicity and rapid identification of genetic variants. We describe an HRM method for the simultaneous screening of exons 8 and 17 KITmutations and report the results obtained in 69 core-binding factor acute myeloid leukemia patients. Mutation detection was compared with sequencing as the gold standard. The HRM method used high-resolution melting master reagents (Roche) and the LightCycler 480 (Roche) platform. HRM was reproducible, showed a lower limit of detection of 1%, and discriminated all patients with mutated KITfrom controls without false positive or false negative results. Additionally, most of the mutations were differentiated from the other mutations. KITmutations were present in 15.9% of patients, showing a higher incidence in inv(16) (25.8%) than in t(8;21) (7.9%). The presence of a KITmutation was associated with a high white blood cell count, and adult patients with an exon 17 mutation had a higher incidence of relapse. These findings verify that HRM is a reliable, rapid, and sensitive method for KITmutation screening. Furthermore, our study corroborates the unfavorable prognosis associated with exon 17 KITmutations.

A previous report of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leukemia results in an improved outcome. Here we analyze treatment outcome of an enlarged series of patients who have been followed up for a median of 65 months. From November 1999 through July 2005 (LPA99 trial), 560 patients received induction therapy with ATRA plus idarubicin. Patients achieving complete remission received 3 courses of consolidation followed by maintenance with ATRA and low-dose chemotherapy. The 5-year cumulative incidence of relapse and disease-free survival were 11% and 84%, respectively. These results compare favorably with those obtained in the previous LPA96 study (P = .019 and P = .04, respectively). This updated analysis confirms the high antileukemic efficacy, low toxicity, and high degree of compliance of a risk-adapted strategy combining ATRA and anthracycline monochemotherapy for consolidation therapy.

A previous report of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-transretinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leukemia results in an improved outcome. Here we analyze treatment outcome of an enlarged series of patients who have been followed up for a median of 65 months. From November 1999 through July 2005 (LPA99 trial), 560 patients received induction therapy with ATRA plus idarubicin. Patients achieving complete remission received 3 courses of consolidation followed by maintenance with ATRA and low-dose chemotherapy. The 5-year cumulative incidence of relapse and disease-free survival were 11% and 84%, respectively. These results compare favorably with those obtained in the previous LPA96 study (P= .019 and P= .04, respectively). This updated analysis confirms the high antileukemic efficacy, low toxicity, and high degree of compliance of a risk-adapted strategy combining ATRA and anthracycline monochemotherapy for consolidation therapy.

All-trans-retinoic acid (ATRA) increases the efficacy of chemotherapy when used for induction and maintenance treatment of acute promyelocytic leukemia (APL), but its role in consolidation is unknown. Since November 1996, 426 patients with newly diagnosed APL have received induction therapy with ATRA and idarubicin. Before November 1999 (LPA96 study), consolidation therapy consisted of 3 courses of anthracycline monochemotherapy. After November 1999 (LPA99 study), patients with intermediate and high risks of relapse received consolidation therapy with ATRA and increased doses of anthracyclines. Of the 384 patients who achieved complete remission (90%), 382 proceeded to consolidation therapy. Seven patients died in remission (1.8%). The 3-year cumulative incidence of relapse for patients in the LPA96 and LPA99 studies was 17.2% and 7.5%, respectively (P= .008). Patients treated with ATRA in consolidation therapy showed an overall reduction in the relapse rate from 20.1% to 8.7% (P= .004). In intermediate-risk patients the rate decreased from 14.0% to 2.5% (P= .006). This improved antileukemic efficacy also translated into significantly better disease-free and overall survival. A risk-adapted strategy combining anthracycline monochemotherapy and ATRA for induction and consolidation therapy of newly diagnosed APL results in improved antileukemic efficacy and a high degree of compliance.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 × 107/kg (range, 1.01 × 107/kg to 4.96 × 107/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 × 109/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 × 109/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P = .01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.

Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RARa-positive APL enrolled in GIMEMA (n?=?108) and PETHEMA (n?=?109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90?±?2% and 86?±?2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count = 10 × 109/L, platelet count > 40 × 109/L), intermediate-risk (WBC count = 10 × 109/L, platelets = 40 × 109/L), and high-risk (WBC count > 10 × 109/L) groups, with distinctive RFS curves (P < .0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease.

The aim of this study is to compare postoperative complications, perioperative course and survival among patients from the multicentric Spanish Video-assisted Thoracic Surgery Group database that received VATS lobectomy (VLG) or VATS anatomical segmentectomy (VASG)

Presentamos el caso de un varón de 71 años diagnosticado de timoma. Se interviene al paciente mediante timectomía con visión mediante toracoscopia e insuflación del mediastino con dióxido de carbono. Durante el procedimiento, en ventilación unipulmonar, el paciente sufre un deterioro respiratorio importante. Se observa el colapso del pulmón debido al paso del dióxido de carbono del mediastino al tórax contralateral por la apertura de la pleura. Se decide volver a la ventilación bipulmonar, con mejoría de la oxigenación en gasometría arterial, presiones en la vía respiratoria y estabilización de pCO2y pH. Se pudo mantener el abordaje y la técnica con dióxido de carbono, puesto que no afectó al campo quirúrgico. Esta técnica presenta complicaciones importantes asociadas, y en caso de realizarse estaría indicado hacerlo en ventilación bipulmonar.

The Spanish PETHEMA group designed a protocol for newly diagnosed PML/RAR?-positive acute promyelocytic leukemia (APL) in which induction and consolidation followed the original AIDA regimen, except for the omission of cytarabine and etoposide from consolidation. Induction consisted of 45 mg/m2 all-trans retinoic acid (ATRA) daily until complete remission (CR) and 12 mg/m2 idarubicin on days 2, 4, 6, and 8. Patients in CR received 3 monthly chemotherapy courses: idarubicin 5 mg/m2/d × 4 (course no. 1), mitoxantrone 10 mg/m2/d × 5 (course no. 2), and idarubicin 12 mg/m2/d × 1 (course no. 3). Maintenance therapy consisted of 90 mg/m2/d mercaptopurine orally, 15 mg/m2/wk methotrexate intramuscularly, and, intermittently, 45 mg/m2/d ATRA for 15 days every 3 months. Between November 1996 and December 1998, 123 patients with newly diagnosed PML/RAR?-positive APL from 39 centers were enrolled. A total of 109 patients achieved CR (89%; 95% confidence interval [CI], 83 to 95), 12 died of early complications, and the remaining 2 were resistant. Consolidation treatment was associated with very low toxicity and no deaths in remission were recorded. Molecular assessment of response by reverse transcriptase-polymerase chain reaction (RT-PCR) showed conversion to PCR-negative in 48 of 99 (51%) and 82 of 88 patients (93%) after induction and consolidation, respectively. The 2-year Kaplan-Meier estimates of overall survival and event-free survival were 82% ± 4% and 79% ± 4%, respectively. For patients who achieved CR, the 2-year disease-free survival (DFS) was 92% ± 3%. These data indicate that a significant reduction in toxicity might be obtained in APL using a less intensive consolidation without apparently compromising the antileukemic effect. These results also suggest a minor role for cytarabine and etoposide in the treatment of newly diagnosed PML/RAR?-positive APL patients.

An observational prospective cohort study was made to evaluate the results of laparoscopic colorectal cancer resection, in terms of recurrence and patient survival. Fifty consecutive patients were analyzed, subjected to abdominoperineal amputations of the rectum (n = 10), anterior rectal resection (n = 13), rectosigmoidectomy (n = 18), and other colectomies (right, left, segmentary) (n = 9). Mean follow-up was 21 months (maximum, 42 months). The tumors corresponded to stage I (TNM classification of the International Union Against Cancer) in 6 cases, stage II in 17, stage III in 18, and stage IV in 9 cases. Survival in stages I-IV was 100, 92, 79, and 18%, respectively, with a disease-free survival rate of 100, 70, and 49% in stages I-III, respectively. Recurrence was pelvic in four cases, with multiple growths, peritoneal carcinomatosis, lung metastases, and implantation in the port scar in one case each. To conclude, survival after a maximum follow-up period of 42 months was found to be acceptable and similar to the percentages reported in the literature for open surgery.

This study evaluates the role of reverse-transcriptase polymerase chain reaction (RT-PCR) assay for carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and maspin transcripts to identify breast cancer cells (BCC) in leukapheresis products (LP) collected from breast cancer (BC) patients and compares these results with those obtained using immunocytochemistry (IC). Eighty-four LP obtained from 33 patients with stage II-III BC and control subjects without BC were screened for the presence of BCC by IC and CK19, CEA, and maspin expression using RT-PCR. CEA RT-PCR and IC were the only specific markers, as no false positives were detected in any patients without BC. CK19 RT-PCR gave 11% false positives, whereas maspin RT-PCR with 25% was the most unspecific marker. In LP from BC patients, positive results were observed in 70% and 63% for CK19 and CEA RT-PCR, respectively. For maspin RT-PCR, this percentage was 22%, and for IC it was 17%. There was a good correlation between the CEA and CK19 RT-PCR (p = 0.018). No correlation between CEA and CK19 RT-PCR and IC was found, and although 5 of the 6 IC+ samples were CEA+/CK19+, great discrepancies in the group of IC- samples were observed. Our data suggest that RT-PCR assays for CEA and, to a lesser extent, for CK19 have more sensitivity and specificity than IC to detect BCC in LP.

Both linoleic acid and cholesterol uptake were studied in small-intestinal sacs of rats in vitro after distal small-bowel resection (DSBR). The relationship between linoleic acid concentration and its absorption was non-linear at low concentrations and became linear at high concentrations in the three groups of animals. These observations indicate that a concentration-dependent dual mechanism of transport is operative in linoleic acid intestinal uptake. Experiments with rotenone and ouabain suggest that a facilitated diffusion is the predominant mechanism of absorption at low concentrations, whereas at high concentrations simple diffusion is predominant. The apparent kinetic constants of linoleic acid uptake (Kd, Kt and Vmax) increased after DSBR. The uptake of linoleic acid is, however, influenced by the simultaneous presence of linolenic acid, the inhibition constant being decreased after the surgical operation. After the surgical operation an increase of cholesterol uptake was observed, with a parallel enhancement in the apparent mass-transfer coefficient (Kd). Taken together, these results suggest that both organ growth and changes in transport function of the enterocytes appear to be involved in the adaptive response of the bowel to intestinal resection.

The effect of coumarin, 4-hydroxycouraarin, coumarin-3-car-boxylic acid and acenocoumarol on the active transport of D-galactose and the passive diffusion of arabinose by intestinal sacs was studied. All these substances, when added to the mucosal medium of incubation at concentrations from 10-4 to 10-3M, inhibit the active transport of D-galactose and increase the diffusion of arabinose.Oxygen uptake by the intestinal tissue is only inhibited by coumarin-3-carboxylic acid.The results suggest that the effects obtained are probably due to an alteration in intestinal permeability, to inhibition of cell metabolism and to molecular size.

AbstractTwo reverse transcription-polymerase chain reaction methods to detect the AML1/ETO rearrangement in the M2 subtype of acute myeloid leukaemia those of Downing et al.(Blood 1993; 81:2860–5) and Satake et al.(Br J Haematol 1995; 91:892–8) were evaluated.Bone marrow samples, one at diagnosis and two in complete remission from a patient with M2 subtype of acute myeloid leukaemia, with t(8;21), were analysed using both methods. The Kasumi-1 cell line was used as a positive control and a patient with M3 subtype of acute myeloid leukaemia as a negative control. To confirm the feasibility of Satake's method a group of 35 patients with subtypes of acute myeloid leukaemia at diagnosis were studied.The method of Downing requires Southern blotting and hybridization with a specific probe because it often generates non-specific amplification products. By contrast, the method of Satake yields only a single amplification product, using one single round of PCR in samples at diagnosis, or two rounds in complete remission samples. The sensitivity of this method allows the detection of a single Kasumi-1 cell in 106normal cells. The AML1/ETO rearrangement was observed in 5 of the 35 cases of acute myeloid leukaemia at diagnosis (14.3%) and in 3 of the 14 cases of M2 subtype of acute myeloid leukaemia (21.4%). The two remaining positive cases corresponded to the acute myeloid leukaemia subtypes M4 and M6. The results indicate that the method of Satake better meets the requirements of the clinical laboratory due to its greater simplicity, specificity, sensitivity and feasibility, thus making it more appropriate for use in diagnosing and monitoring minimal residual disease.