Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Awareness of obstetric warning signs in Ecuador: a cross-sectional study.

OBJECTIVE: In Ecuador, the reported maternal death rate was 45.71 per 100,000 live births in 2013. This may be partly due to a lack of maternal knowledge of obstetric warning signs during pregnancy, delivery and the post-partum period. This study sought to evaluate awareness of obstetric warning signs among pregnant women in relation to individual demographic and area-level socio-economic indicators. STUDY DESIGN: We conducted a cross-sectional analysis of data collected by Ecuador's Ministry of Health at the conclusion of a national maternal health campaign (2014-2015). A nationally representative sample of 3435 pregnant women from the nine administrative zones completed surveys regarding basic demographics and their awareness of obstetric warning signs. METHODS: We defined eight obstetrical warning signs according to the literature and Ecuadorian practice that could occur during pregnancy, delivery and the post-partum period (severe headache, strong abdominal ache, bleeding or presence of malodorous secretion, rupture of the amniotic sac, high fever, abnormal presentation of the baby, decrease in baby's movements and delayed labour). A woman was considered 'aware' if she recognised at least four of the eight warning signs and stated she would seek immediate healthcare at their presentation. For each administrative zone, four socio-economic indicators (poverty, illiteracy, unemployment and subemployment) were obtained from the National Institute of Statistics and Census. Correlates of awareness of the obstetric warning signs were evaluated using hierarchical logistic models clustered by the administrative zone. RESULTS: Nationally, 86.9% of women were 'aware' of obstetric warning signs. After adjustment for age, socio-economic indicators and clustering, indigenous participants were 59% less likely to be aware of obstetric warning signs than mestizos (odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.28-0.59). For every 1% increase in area poverty, participants had a 5% decreased likelihood of being aware of obstetric warning signs (OR = 0.95, 95% CI = 0.93-0.96), adjusting for age, ethnicity and other socio-economic indicators. The most effective source of campaign information about obstetric warning signs was personal communication with a healthcare professional, as opposed to mass media advertisements (OR = 1.90, 95% CI = 1.34-2.71). CONCLUSIONS: A majority of Ecuadorian pregnant and post-partum women are aware of obstetric warning signs. Indigenous ethnicity and area-level poverty are associated with a lack of awareness. Personal communication with a healthcare professional was the most effective source of information. These findings have implications for improvement of maternal awareness of warning signs.

Identifying prognostic gene panels in acute myeloid leukemia.

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous disease currently including 12 entities defined by genetic findings with remarkable differences in prognosis and targeted therapies availability. Therefore, identification of genetic abnormalities by efficient techniques has become a necessary tool in routine clinical practice for AML patients. AREAS COVERED: In the present review, we will focus on our current knowledge of relevant prognosis gene mutations in AML, as recently updated by European Leukemia Net Leukemia risk classification. EXPERT OPINION: About 25% of newly diagnosed younger AML patients will be promptly classified as favorable prognosis by demonstrating the presence of NPM1 mutations or CBF rearrangements by qRTPCR, allowing for implementing molecular measurable residual disease-guided chemotherapy-based protocols. In fit AML patients, rapid detection of FLT3ITD is mandatory to associate midostaurin or quizartinib to treatment and assignment to intermediate prognosis. Conventional cytogenetics and FISH still have a role for detection adverse prognosis karyotypes and KMT2A, MECOM, or NUP98 gene rearrangements. Further genetic characterization is performed with NGS panels including favorable prognosis gene CEBPA bZIP and adverse prognosis genes, such as TP53 and myelodysplasia associated genes.

Achromobacter xylosoxidans bacteremia: clinical and microbiological features in a 10-year case series.

OBJECTIVE: The treatment of Achromobacter xylosoxidans bacteremia is challenged by antimicrobial resistance and the paucity of data. We aimed at offering a contemporary description of this uncommon entity. METHODS: Retrospective case series of 13 episodes of A. xylosoxidans bacteremia diagnosed over a 10-year period (November 2007 to May 2017) in our tertiary care center. RESULTS: Solid organ cancer and heart failure were the most common comorbidities (4/13 [30.7%]). All but one episodes were hospital-acquired. Most patients had received previous antibiotic therapy (7/13 [53.8%]) and had a central venous catheter in place (6/13 [46.1%]). Primary and intravascular catheter were the most common sources (4/13 [30.7%] each). Meropenem was the agent with best in vitro activity (92.3% [12/13] of susceptible isolates). All-cause 30-day mortality (overall 23.1%) was higher in patients with primary bacteremia (50.0% vs. 11.1%; P-value=0.203) and prior chemotherapy (66.7% vs. 10.0%; P-value=0.108). CONCLUSIONS: Bacteremia due to A. xylosoxidans constitutes a serious infection among immunocompromised hosts. Carbapenem-based therapy may be appropriate in most cases.

Prolonged molecular remission after PML/RAR alpha-positive autologous peripheral blood stem cell transplantation in acute promyelocytic leukemia: is relevant pretransplant minimal residual disease in the graft?

The contribution of residual malignant cells contaminating the autologous graft with the occurrence of post-transplant relapse in acute myeloid leukemia (AML) is still unclear. The presence of a specific molecular marker (the PML/RAR alpha rearrangement) in acute promyelocytic leukemia (APL) offers the opportunity to investigate better the pathogenesis of disease recurrence after transplant. We report an APL patient who received high-dose chemotherapy and peripheral blood stem cell (PBSC) autograft in second hematologic remission. Two leukaphereses that tested PML/RAR alpha positive by RT-PCR were obtained during the post-reinduction hematopoietic recovery, while the patient also tested PCR positive in the BM, and was reinfused after myeloablative chemotherapy (BUCY4), when the patient had spontaneously converted to PCR negative in the marrow. At present, he remains in continuous molecular and hematologic remission 22 months after PBSC transplantation. This is the second report of an APL patient who was transplanted in molecular remission with a PML/RAR alpha-positive PBSC autograft. As in the previous report, the prolonged clinical and molecular remission experienced post-transplant suggests that autologous PBSC infusion is still worthy of consideration for patients with APL in spite of the detection of PML/RAR alpha-positive cells in the PBSC collections. Possible underlying mechanisms and the potential role of molecular monitoring of the graft, as well as the host, before and after transplant, in patients with APL undergoing autologous HSCT are also discussed.

Preliminary experience in external quality control of RT-PCR PML-RAR alpha detection in promyelocytic leukemia.

To standardize the results obtained in PML/RAR alpha RT-PCR detection by laboratories of hospitals involved in the Spanish Program for Treatment of Hematological Malignancies (PETHEMA) LPA-96, designed for the treatment of acute promyelocytic leukemia (APL), cDNA samples obtained by reverse transcription of RNA from bone marrow samples of patients with APL were sent to participating laboratories. During the first year of this external quality assessment trial nine samples were tested by a maximum of 12 laboratories. The control gene was satisfactorily amplified in 90% of the samples (62 of 69 samples), supporting the adequacy of the cDNA to be used as control sample. There was an 83% concordance between laboratories for PML/RAR alpha detection with similar results for the type of PML/RR alpha rearrangements. However, 17% disagreement still remained, attributable to low sensitivity or inadequacy of methods followed. The results stressed the need for implementation of an external quality assessment scheme to ensure the standardization of the results.

Chronic myeloid leukemia with expression of ALL-type BCR/ABL transcript: a case-report and review of the literature.

CML with exclusive expression of ALL-type bcr/abl has only been rarely described. In some cases, the presence of this fusion gene has been associated to a differentiated subtype of CML that share some features with CMML, while in another case this molecular hallmark has been associated to a bad prognosis of the disease with a blast phase as clinical presentation or an early transformation to blast phase. We report a case of a 30-year-old woman who was diagnosed of CML in chronic phase in May 1989. She received treatment first with busulfan, achieving hematological remission and afterwards with interferon and Hydroxiurea. In February 1998, she was admitted at our hospital for an ABSCT. Then, molecular studies were performed. Multiplex PCR revealed the presence of a 481 bp product identified as the ela2 bcr/abl transcript and confirmed by sequencing. After 9 years from diagnosis, the patient remains in hematological remission and in good clinical condition.

Mechanical performance of acrylic bone cements containing different radiopacifying agents.

The effect that three different radiopacifying agents, two of them inorganic (BaSO4, ZrO2) and one organic (an iodine containing monomer, IHQM) have on the static and dynamic mechanical properties of acrylic bone cements was studied. Compressive and tensile strength, fracture toughness and fatigue crack propagation were evaluated. The effect of the inorganic fillers depends on their size and morphology. In relation to the radiolucent cement, the addition of zirconium dioxide improved significantly the tensile strength, the fracture toughness and the fatigue crack propagation resistance. In contrast, the addition of barium sulphate produced a decrease of the tensile strength, but did not affect the fracture toughness and improved the crack propagation resistance. When the iodine containing monomer was used, although the tensile strength and the fracture toughness increased, the fatigue crack propagation resistance remained as low as it was for the radiolucent cement.

Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults is not well established. We report the results of UD-CBT in nine adult patients with chronic myeloid leukemia (CML). The median age was 27 years (range, 19-41 years), and the median weight was 62 kg (range, 45-78 kg). At transplant, six patients were in chronic phase (five in first, and one in second), two in blast crisis, and one in accelerated phase. Eight had received intensive chemotherapy, and three had undergone autologous peripheral blood hematopoietic stem cell transplantation. Four had received interferon with no cytogenetic response, and only three underwent UD-CBT within 1 year of diagnosis. After serological typing for class I antigens, and high-resolution DNA typing for DRB1, the degree of HLA match between patients and cord blood (CB) units was 4/6 in six cases and 5/6 in three cases. The median number of nucleated cells infused was 1.7 x 10(7)/kg (range, 1.2 to 4.9 x 10(7)/kg), and was above 2 x 10(7)/kg in only two cases. All patients received thiotepa, busulfan, cyclophosphamide and anti-thymocyte globulin as conditioning; cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis; and G-CSF from day +7 until engraftment. All seven evaluable cases engrafted. The median time to reach an absolute neutrophil count > or =0.5 x 10(9)/l and > or =1 x 10(9)/l was 22 days (range, 19-52 days) and 28 days (range, 23-64 days), respectively. In the four patients evaluable for platelet recovery time to levels of > or =20 x 10(9) platelets/l, > or =50 x 10(9) platelets/l, and > or =100 x 10(9) platelets/l, these ranged from 50 to 128 days, 60 to 139 days, and 105 to 167 days, respectively. Three patients developed acute GVHD above grade II, and three of the five patients at risk developed extensive chronic GVHD. Four patients, all transplanted in chronic phase, remain alive in molecular remission more than 18, 19, 24 and 42 months after transplantation. These preliminary results suggest that UD-CBT may be considered a reasonable alternative in adults with CML who lack an appropriate bone marrow donor.

Variant three-way translocation of inversion 16 in AML-M4Eo confirmed by fluorescence in situ hybridization analysis.

The inv(16) and t(16;16) characterize a subgroup of acute myelomonocytic leukemia (AML) with distinct morphological features and a favorable prognosis. Both cytogenetic abnormalities result in a fusion of CBF beta at 16q22 and MYH11 gene at 16p13, whose detection by PCR and fluorescence in situ hybridization (FISH) is useful for diagnosis and monitoring of the disease. Variant translocations of inv(16)/t(16;16) are very rare and whether they are also associated with a favorable prognosis is unknown. We report a patient presenting with typical AML-M4Eo and a three-way translocation of inv(16) involving 16p13, 16q22, and 3q22. FISH studies on bone marrow (BM) chromosomes using CBFB and MYH11 DNA probes revealed a fusion of CBFB and MYH11 on 16q of the der(16), as well as a signal from MYH11 on 16p but not from CBFB; normal signals for both probes were present on the normal 16. Neither of these labeled probes was on the der(3), but the translocation between the der(3) and der(16) was confirmed by using a chromosome 16 painting probe. Molecular analysis of BM cells using RT-PCR identified a CBFB-MYH11 fusion transcript type D. After achieving complete remission, the patient relapsed. We conclude that FISH and PCR are feasible tools to distinguish cases with variant abnormalities of inv(16) from cases with other chromosome 16 abnormalities. Variant abnormalities of inv(16) may be not associated with favorable prognosis.

Quantitative detection of AML1-ETO rearrangement by real-time RT-PCR using fluorescently labeled probes.

The persistence of the AML1-ETO rearrangement performed by reverse transcription polymerase chain reaction (RT-PCR) has been reported in acute myeloid leukemia (AML) patients in long-term complete remission (CR). This persistence, which is not associated with hematological relapse, limits the clinical use of qualitative RT-PCR. Here, we present a new quantitative real-time PCR method to detect AML1-ETO rearrangement using fluorescently labeled probes. Quantitative detection of AML1-ETO was performed in capillary tubes using two fluorescently labeled probes in the LightCycler equipment. The reliability of the method was checked in twenty-two bone marrow samples and one apheresis sample from eight patients with t(8;21) collected at diagnosis and during follow-up assessment. The regression coefficients obtained for standard curves of AML1-ETO and AML were all greater than 0.98. The sensitivity attained allowed the detection of rearrangements at a dilution of 10(-5) Kasumi-1 cDNA. The intra-assay coefficient of variation was 4% for AML1-ETO, and 7% for AML. The inter-assay coefficient of variation was 19% for AML1-ETO and 12% for AML. A log reduction from two to four in the AML1-ETO/AML ratio was evident after CR. The study of the method and first results obtained in patient samples support that quantitative real-time PCR with hybridization probes is a new reliable and sensitive method to monitor minimal residual disease in AML patients. Moreover, the fluorescent probes with the Light-Cycler technology offer the advantage of a rapid detection.

Electrophysiological connections of neurons in ventral pallidal regions of the olfactory tubercle with the main olfactory bulb and piriform cortex.

Field potential and single unit recordings were used to assess the connections of the olfactory tubercle (OT) with the main olfactory bulb (MOB) and the piriform cortex (PC) in urethane-anesthetized rats. Current generators of depth profiles evoked in OT following MOB stimulation were localized 300 microns superficial to those elicited by PC shocks, suggesting that afferents from the MOB and PC end in different regions of the OT. Following MOB and PC stimulation antidromically invaded neurons were recorded in the ventral pallidal regions of the OT and in the vicinity of the islands of Calleja, respectively. These results demonstrate that the OT, which receives a monosynaptic input from the MOB, projects back to the bulb and that the PC seems to be also reciprocally linked with differentiated structures in the OT.

Cortical and quasi-cortical regions innervate ventrostriopallidal structures in the rat: an electrophysiological analysis.

Antidromic unit driving was utilized to demonstrate afferent projections from prefrontal cortical (PFC) and quasi-cortical structures (main olfactory bulb, MOB; anterior olfactory nucleus, AON; basolateral amygdaloid nucleus, BLA) to the ventrostriopallidal region (VSPR) of the rat. In all regions explored, a substantial number of antidromically invaded neurons were found following electrical stimulation of the VSPR. In addition, both the AON and the amygdalostriatal zone harbor cells with branched axons which innervate the MOB and the VSPR and the agranular insular cortex and the VSPR, respectively. These results support and extend previous neuroanatomical and neurophysiological data on afferent connections of the VSPR and emphasize the fact that several regions of the basal forebrain, which are actively involved in processing of olfactory information, and the VSPR, are more closely interrelated than hitherto suspected.

Ventrostriopallidal functional interconnections with cortical and quasi-cortical regions.

A total of 287 neurons were antidromically driven in quasi-cortical regions, i.e., anterior olfactory nucleus (24%), basolateral amygdala (13%), main olfactory bulb (4%), prefrontal cortex (37%), and in the hippocampal formation (22%) following macro- and microstimulation of the rat's ventrostriopallidal region (VSPR). In addition, a substantial number of units (n = 175) were also transynaptically affected in all these structures by shocks delivered to the VSPR. Excitatory effects were detected in 50 neurons (56.1% of responsive cells), 36 cells (40.4%) responding with inhibition of spontaneous discharges. Conversely, stimulation of cortical and quasi-cortical regions antidromically discharged (n = 37) or transynaptically affected (n = 151) units in the VSPR; 168 neurons were not responsive to VSPR stimulation. Axon collateralization (branching) of 14 neurons in anterior olfactory nucleus, basolateral amygdala, and hippocampal formation was revealed with the use of the reciprocal collision test. Conduction properties of 35 neurons, evaluated by paired-pulse stimulation, indicated that only 26% showed a significant increase in conduction velocity and a decrease in threshold during the supernormal phase. The present findings confirm and extend previous neuroanatomical studies that have, first, described strong interconnections between the neocortex and striatal structures, and second, that the VSPR as suggested by previous structural, hodological, and histochemical studies, seems to maintain a more close relationship with olfactory related structures than hitherto suspected.

Reciprocal functional connections of the olfactory bulbs and other olfactory related areas with the prefrontal cortex.

Reciprocal putative connections of the prefrontal cortex (PFC) (agranular insular, ventral and lateral orbital region) with the ipsi and contralateral main olfactory bulb (IOB; COB), the mediodorsal thalamic nucleus (MD), the basolateral amygdaloid nucleus (BLA) and the piriform cortex (PC) were investigated with electrophysiological techniques. Evoked field responses and orthodromic unit driving, generated in PFC following electrical stimulation of the above mentioned structures, were abolished following topical application of KCl, except for COB evoked mass potentials. Thus, locally generated activity was elicited in agranular insular cortex following IOB activation, the same region where recently, the taste cortex in the rat was localized. Since gustatory-visceral afferent information reaches insular cortex via 2-3 synaptic relays, autonomic, olfactory and gustatory inputs may interact at this level, and, as suggested previously for the mouse, play a key integrative role in flavor perception. Antidromically invaded neurons, 47% of which were identified by the collision-extinction technique, were also found in PFC areas which overlapped to a considerable extent with those from which orthodromic unit responses were obtained. In particular, closely spaced neurons in ventrolateral orbital (VLO) and lateral orbital (LO) regions were antidromically invaded following IOB and PC shocks; some neurons antidromically discharged by IOB were also transsynaptically activated following PC stimulation. These findings are in agreement with recent neuroanatomical studies which demonstrate axonal projections from PFC neurons to the IOB and COB in the rat and South American armadillo. In addition, stimulation of PFC regions dorsal to the rhinal fissure mostly inhibited spontaneous unit discharges recorded at the mitral cell layer of the IOB, suggesting that this effect may be partially mediated by excitatory inputs of prefrontal axons onto granule cells. The conduction properties, antidromic thresholds and activity-dependent variations in conduction velocity (CV) of bulbopetal neurons in prefrontal cortex were found to be similar to those exhibited by cells projecting to the IOB from olfactory peduncle regions, but not to those present in bulbopetal neurons of the horizontal limb of diagonal band, indicating that the OB may be subjected to centrifugal control by at least two cell groups differing in both histochemical and electrophysiological properties.

Current generators and properties of late components evoked in rat olfactory cortex.

Following main olfactory bulb (MOB) stimulation at frequencies of 0.1-0.3 Hz, in addition to early field potentials, a frequency-sensitive, surface negative late N2 wave (latency range: 63-96 msec) followed occasionally by a late N3 transient, was evoked in the piriform cortex and endopiriform nucleus of the rat. The N2 wave inverted polarity at the Ib-II cortical layer interface (P2 wave) and was associated with late unit discharges 200 to 1200 microns deep to the turnover point. Response probability, peak latency, recovery curve and frequency-sensitivity of the P2 wave were not significantly different in animals under urethane or pentobarbital. Current-source-density (CSD) analysis revealed that the N2 wave generators were localized to the Ib-II layer interface. Since inhibitory activity does not contribute substantially to the second derivative curve, CSD analysis strengthens the assumption that late components (LCs) are excitatory events (compound EPSPs) presumably generated on the proximal apical dendritic segments of pyramidal cells by association axons. The early "b" wave in a test response was facilitated, rather than occluded, when a LC was present in the conditioning response, or when the priming volley was delivered to the mediodorsal thalamic nucleus. Clustering of unit and field activity in two distinct periods of the evoked response separated by a prolonged interval of cell silence suggests that cortical coding of olfactory cues might be more efficiently achieved by temporal modulation of the neuronal response rather than by spatial distribution of firing patterns.

Prognostic significance of c-erbB-2/neu amplification and epidermal growth factor receptor (EGFR) in primary breast cancer and their relation to estradiol receptor (ER) status.

The aim of this study is to evaluate the prognostic significance of c-erbB-2/neu amplification and epidermal growth factor receptor (EGFR) expression in primary breast cancer (BC) and their prognostic implications when combined with estradiol receptor (ER) status. In this work, 825 BCs were studied. Neu amplification was evaluated by dot-blot and EGFR expression was evaluated by ligand binding assay using I125-EGF. Neu, EGFR, estradiol and progesterone receptors (ER and PR) had a marked influence on disease free survival (DFS) in univariate analysis. In node-negative (NO) cases only neu was associated with short DFS (p = 0.005). However, in node-positive (N+) cases both EGFR (p = 0.005) and neu (p = 0.002) influenced DFS. None of the biological markers were significant predictors for overall survival (OS) in NO/BC. On the contrary, in N+/BC, EGFR + (p = 0.003) was associated with short OS. The EGFR + /neu/phenotype represented a sub-group with an even worse prognosis with respect to DFS (p = 0.0034) as well as EGFR + /ER-tumors (p = 0.005). Moreover, neu + /ER-patients also had a high probability of relapse (p = 0.0000) and death (p = 0.006). C-erbB-2/neu, EGFR, histological grade, pN, pT and ER were subjected to a Cox multivariate regression analysis: neu was the most important parameter in predicting recurrence, and EGFR was a significant predictor for OS.

[Monitoring of minimal residual disease with the combined detection of PML/RAR alpha and RAR alpha/PML rearrangements in acute promyelocytic leukemia]. / Monitorización de la enfermedad mínima residual mediante detección conjunta de los reordenamientos PML/RAR alpha y RAR alpha/PML en la leucemia promielocítica aguda.

BACKGROUND: Molecular assay commonly used to detect the PML/RAR alpha rearrangement in acute promyelocytic leukemia (APL) has the limited sensitivity in comparison with the higher sensitivity of RAR alpha/PML detection. This prompted us to perform both assays in parallel to monitor a group of APL. PATIENTS AND METHODS: The study included 56 APL patients mainly treated according with the PETHEMA LPA-96 protocol. The PML/RAR alpha was detected according with Biondi's et al method and the RAR alpha/PML following the Grimwade's et al RT-PCR method (Human Press Inc.). RESULTS: RAR alpha/PML rearrangement was detected in 90% (20/22) of the patients at diagnosis positives for PML/RAR alpha. RAR alpha/PML was detected in 74% (14/19) of post-induction samples versus 37% (7/19) of positives for PML/RAR alpha. Likewise RAR alpha/PML rearrangement was detected in some post-consolidation samples (2/11) that all were PMI/RAR alpha negatives. In patients in maintenance regimen a greater proportion of RAR alpha/PML positives (6/28) versus PML/RAR alpha (2/28) were observed. In a patient in complete remission RAR alpha/PML preceded the positivity of PML/RAR alpha and persisted after PMI/RAR alpha negativization. The results of the patients monitored since the diagnosis showed that RAR alpha/PML revert to negative one month after PML/RAR alpha negativization. CONCLUSIONS: RAR alpha/PML rearrangement is not expressed in the totality of the APL patients, but in only a 90% of them. RAR alpha/PML rearrangement was detected in a greater proportion of samples than PML/RAR alpha. RAR alpha/PML rearrangement lasted longer than PML/RAR alpha after treatment.

Effect of aluminium and sulphate on anaerobic digestion of sludge from wastewater enhanced primary treatment.

The combined and individual effects of aluminium and sulphate at concentrations of 1,000 mg/l as Al(OH)3, and 150 mgSO4(2-)/L as K2SO4, respectively, on the anaerobic digestion of sludge from enhanced primary treatment (EPT) were evaluated in 1 L capacity semi continuous reactors. It was found that at 59 days, aluminium inhibits the specific methanogenic activity (SMA) of methanogenic and acetogenic bacteria resulting in a 50% to 72% decrease. Sulphate also inhibits (48% to 65%) the SMA of the same type of bacteria. Methanogenic and acetogenic bacteria were able to adapt, to a different extent, to the assayed concentrations of aluminium and sulphate. However, the combination of aluminium and sulphate resulted in a higher inhibition, especially of the hydrogenophilic methanogenic bacteria. Indeed, this effect remained during the time of the experiment, maintaining an inhibition of 44% at 114 days. Feeding with EPT sludge led to a bigger decrease in SMA of each bacterial group, with respect to the other treatments with time. It is concluded that the acidification of anaerobic reactors fed with EPT sludge is due, among other causes, to the concurrent presence of aluminium and sulphate.

Lich-Gregoir technique and routine use of double J catheter as the best combination to avoid urinary complications in kidney transplantation.

INTRODUCTION: Urinary complications in kidney transplantation cause patient morbidity and can decrease graft survival. Most of the complications stem from the vesicoureteric anastomosis. Different techniques for ureteroneocystostomy (UNC) have been designed to avoid these complications. The routine use of a double J catheter after the anastomosis has the same purpose. Our aim was to show our experience and compare the use or non-use of a double J catheter and different techniques for ureteric reimplantation with the rate of urologic complications. MATERIAL AND METHODS: We conducted a retrospective, nonrandomized study of 1011 renal transplantations performed between July 1985 and April 2012. We recorded the surgical techniques for UNC, the use or non-use of a double J catheter, and urinary complications (ureteric fistulae and strictures). The first 700 kidney transplantations (group A) were performed using several UNC techniques (Taguchi, Leadbetter-Politano, and Lich-Gregoir) with a selective use of double J catheter according to the criteria of the surgeon. In the last 311 patients (group B), a surgical technique was established (Lich-Gregoir), as well as the universal use of double J catheters. RESULTS: Urinary fistula occurred in 7% of group A patients and 2% of group B patients (P = .0001). Ureteric stricture occurred in 5.3% of patients in group A and 3% of group B patients (P = .09). In our study, routine prophylactic stenting combined with the Lich-Gregoir UNC technique has decreased the incidence of postoperative fistulae. CONCLUSIONS: Individually, the use of double J catheters seems to lessen the incidence of fistulae, although statistically, the difference is not significant. Accurate knowledge of the complications rates, recommendations of guidelines, and the early diagnosis are essential to attaining reasonable results in kidney transplantation.