The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Plerixafor in patients with lymphoma and multiple myeloma: effectiveness in cases with very low circulating CD34+ cell levels and preemptive intervention vs remobilization.

This retrospective study presents data from 105 consecutive multiple myeloma and lymphoma patients who had PB CD34+ cell counts <10/µL on day 4 of steady-state G-CSF mobilization for autologous hematopoietic cell transplantation. Our results confirm the capacity of plerixafor to improve mobilization outcomes in this clinical setting. In addition, they show that the effectiveness of plerixafor, compared with G-CSF only, translates to patients with very low (<3.5/µL) circulating CD34+ cell counts: overnight CD34+ cell count expansion (5.3- vs 1.7-fold), overall CD34+ cell yield (2.29 vs 0.15 × 10(6) CD34+ cells per kg) and patients yielding ⩾2 × 10(6) CD34+ cells per kg (63% vs 3%). Furthermore, our data also show that preemptive plerixafor is significantly more effective and more efficient than in remobilization: CD34+ cell yield in the first apheresis (3.28 vs 2.0 × 10(6) CD34+ cells per kg) and overall (3.73 vs 2.44 × 10(6) CD34+ cells per kg), patients yielding ⩾2 × 10(6) CD34+ cells per kg in the first apheresis (85% vs 44%) and overall (92% vs 64%), all this requiring less days and doses of plerixafor treatment (1.08 vs 1.48). These data would advocate using plerixafor as an early preemptive intervention based on day 4 circulating CD34+ counts, including very high-risk patients with very low circulating levels.

Low-dose beta-lactam plus amikacin in febrile neutropenia: cefepime vs. piperacillin/tazobactam, a randomized trial.

Patients with fever and granulocytopenia are at risk of developing severe infection. We performed a prospective, randomized trial to evaluate the efficacy of low-dose cefepime plus amikacin (C-A) compared to low-dose piperacillin/tazobactam plus amikacin (PT-A). Patients received cefepime (2 g/12 h) plus amikacin (15 mg/kg/day) or piperacillin/tazobactam (4 g/500 mg/8 h) plus amikacin. A total of 317 episodes of febrile granulocytopenia in 190 patients were studied (152 in the C-A group, 165 in the PT-A group). A microbiologically documented infection was present in 53 (35%) episodes in the C-A group and 41 (25%) episodes in the PT-A group (p = ns); a clinically documented infection was observed in 39 (26%) and 47 (28%) episodes, respectively. Toxicity was observed in 6 (4%) episodes in the C-A group and in 5 (3%) episodes in the PT-A group. The antibiotic success rate (no change or addition of antibiotics) was recorded in 89 (59%) and 105 (64%) cases, respectively (p = ns). Mortality related to infection was similar in each arm (3.9% vs. 3.6%). Combination therapy of low-dose beta-lactam with an aminoglycoside achieves very good response rates and low rates of toxicity. It might be an attractive option in an environment of increasing resistance among gram-negative bacteria.

Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level >0.1% at the end of treatment than in patients with < or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of >10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.

Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute myeloid leukemia patients.

BACKGROUND AND OBJECTIVES: A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. DESIGN AND METHODS: Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. RESULTS: CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CONCLUSIONS: CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.

Leprosy: dental and periodontal status of the anterior maxilla in 76 patients.

OBJECTIVE: To evaluate the presence of oral disease, as assessed by dental and periodontal indices, in the anterior maxilla of a group of 76 patients with leprosy, compared with a group of matched control subjects. MATERIALS AND METHODS: The study included 76 patients with leprosy (age range 40-82 years; 39 males), resident in the sanatorium of San Francisco de Borja de Fontilles (Alicante, Spain). Clinical examination was carried out to evaluate the decayed missing and filled index, and the periodontal status in the anterior maxilla, using the Löe-Silness dental plaque index, mean periodontal probing depth and the average periodontal attachment loss. RESULTS: In the leprosy patients, a large proportion of maxillary incisors and canines were missing. The mean plaque index in leprosy was 2.35 +/- 0.7, with a probing depth of 2.96 +/- 0.8, and an average attachment loss of 4.18 +/- 1.3, indices all statistically greater than in controls. There were no differences detected in the oral indices measured according to the presence or absence of facial destruction or the type of leprosy. CONCLUSIONS: Patients with leprosy show a tendency to poor dental and periodontal health, unrelated to the presence of facial destruction or the type of leprosy.

[Clinical value of positron emission tomography with F-18-FDG in the follow up of patients with cancer of the ovary]. / Valor clínico de la tomografía de emisión de positrones con F-18-FDG en el seguimiento de pacientes con cáncer de ovario.

BACKGROUND: Positron emission tomography with fluor-18-deoxyglucose (PET-FDG) is an efficient technique for the detection of tumoural tissue. The aim of the paper is to evaluate the PET-FDG in the diagnosis of residual disease or relapse in patients with cancer of the ovary. METHODS: A total of 24 patients, diagnosed and treated for cancer of the ovary with surgery and subsequent chemotherapy, were included. With 12 patients the study was carried out prior to second-look surgery, and with the other 12 after objectivising an increase of the tumoural marker in the follow up. Abdominal-pelvic CAT, determination of the seric levels of CA-125 and PET-FDG of thorax, abdomen and pelvis were carried out on all patients. The PET-FDG was evaluated in a qualitative way through the visual study of the images, and quantitatively through the SUV or standard uptake value. The definitive diagnosis was confirmed through an anatomopathological study in 13 cases and through clinical follow up in the rest with an average of 11.2+/-5.4 months (range 6-24). RESULTS: A CA-125 value higher than 35 UI/ml was considered positive, obtaining a sensitivity of 77% and a specificity of 100%. The sensitivity of the CAT was 23% and the specificity 91%. With the FDG-PET sensitivity was 92% and the specificity 90%. A SUV value >or= 3 was considered pathological, obtaining the same results as with the visual evaluation. The FDG-PET was positive in 5 patients with non-conclusive CAT, 4 with negative CAT and 2 with negative CA-125. CONCLUSION: These preliminary results suggest that the FDG-PET could be useful in the detection of disease in the follow up of patients treated for cancer of the ovary. The FDG-PET could be efficient in the differentiation between residual disease or recurrence, as opposed to sequels to the treatment, when the CAT is not conclusive due to anatomical distortion, since it permits the detection of tumoural lesions undetected by the radiological image techniques but metabolically active. The FDG-PET could be more sensitive than an increased marker value, and facing an increase of the latter it permits a non-invasive localisation of the disease.

Synthesis and reactivity of bridging and terminal hydrosulfido palladium and platinum complexes. Crystal structures of [NBu4]2[(Pt(c6F5)2(mu-SH)]2], [Pt(C6F5)2(PPh3)[S(H)AgPPh3]], and [Pt(C6F5)2(PPh3)[S(AuPPh3)2]].

The reactions of the hydroxo complexes [M(2)R(4)(mu-OH)(2)](2)(-) (M = Pd, R = C(6)F(5), C(6)Cl(5); M = Pt, R = C(6)F(5)), [[PdR(PPh(3))(mu-OH)](2)] (R = C(6)F(5), C(6)Cl(5)), and [[Pt(C(6)F(5))(2)](2)(mu-OH)(mu-pz)](2-) (pz = pyrazolate) with H(2)S yield the corresponding hydrosulfido complexes [M(2)(C(6)F(5))(4)(mu-SH)(2)](2-), [[PdR(PPh(3))(mu-SH)](2)], and [[Pt(C(6)F(5))(2)](2)(mu-SH)(mu-pz)](2-), respectively. The monomeric hydrosulfido complexes [M(C(6)F(5))(2)(SH)(PPh(3))](-) (M = Pd, Pt) have been prepared by reactions of the corresponding binuclear hydrosulfido complexes [M(2)(C(6)F(5))(4)(mu-SH)(2)](2-) with PPh(3) in the molar ratio 1:2, and they can be used as metalloligands toward Ag(PPh(3))(+) to form the heterodinuclear complex [(C(6)F(5))(2)(PPh(3))[S(H)AgPPh(3)]], and toward Au(PPh(3))(+) yielding the heterotrinuclear complexes [M(C(6)F(5))(2)(PPh(3))[S(AuPPh(3))(2)]]. The crystal structures of [NBu(4)](2)[[Pt(C(6)F(5))(2)(mu-SH)](2)], [Pt(C(6)F(5))(2)(PPh(3))[S(H)AgPPh(3)]], and [Pt(C(6)F(5))(2)(PPh(3))[S(AuPPh(3))(2)]] have been established by X-ray diffraction and show no short metal-metal interactions between the metallic centers.

[Clinical characteristics of 104 patients with obsessive compulsive disorder]. / Características clínicas de 104 pacientes con diagnóstico de trastorno obsesivo compulsivo.

INTRODUCTION: Obsessive compulsive disorder is a common disorder, but research on its clinical features is scarce. The goal of this study is to describe the clinical characteristics and demographic features of a large sample of patients with Obsessive compulsive disorder. METHOD: The characteristics of 104 patients who sought psychiatric treatment and who were diagnosed as having Obsessive compulsive disorder were assessed by means of a structured questionnaire. RESULTS: The mean age of onset was 20 years and the mean time before soliciting treatment was 4 years. Most of the patients reported an insidious onset and related the onset to an stressful event. The most frequent obsessions were doubt, aggressiveness and contamination. Checking, need to ask and mental rituals were the most frequent compulsions. Cleaning and repetition compulsions were most frequent in women. DISCUSSION: Our results regarding age at onset of illness, way of onset or prevalence of certain obsessions and compulsions are similar to previous research. No agreement was obtained with previous research regarding the link between stress and illness onset, the course of the disorder or the time before treatment was sought. The differences with respect to previous studies could be accounted for the use of different instruments or criteria. The need for the development of instruments allowing to shed light on these discrepancies is stressed.

Increased conventional chemotherapy does not improve survival in multiple myeloma: long-term results of two PETHEMA trials including 914 patients.

BACKGROUND: Melphalan and prednisone (MP) has been the standard treatment for multiple myeloma (MM) for the last 30 years. Combination chemotherapy at conventional doses has not shown a significant prolongation of survival when compared to MP. There are few data comparing conventional chemotherapy at standard doses with conventional treatment at higher doses. We present the long-term outcome of 914 patients from two randomized trials comparing three different dose intensity regimens. METHODS: From 1 January, 1985 to 31 December, 1989, 487 patients were randomized between MP (melphalan 9 mg/m(2) p.o. and prednisone 60 mg/m(2) days 1-4) and alternating VCMP (vincristine 1 mg i.v. on day 1, cyclophosphamide 500 mg/m(2) i.v. on day 1, melphalan 6 mg/m(2) p.o. on days 1-4, and prednisone 60 mg/m(2) on days 1-4) and VBAP (vincristine 1 mg i.v. on day 1, BCNU and doxorubicin 30 mg/m(2) i.v. each on day 1, and prednisone 60 mg/m(2) on days 1-4). From 1 January, 1990 to 31 May, 1994, 427 patients were randomized between VCMP/VBAP at the above detailed doses (VCMP/VBAP 'SD') and the same regimen increasing the doses of cyclophosphamide and doxorubicin from 500 to 1200 mg/m(2) and from 30 to 50 mg/m(2), respectively (VCMP/VBAP 'HD'). RESULTS: Increasing dose intensity produced a significantly higher partial response rate (31% vs 45% vs 51% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P < 0.01). However, a significantly early death rate was observed in the HD arm (7.7, 7.5 and 12.1% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = 0.05). Median duration of response (20 vs 18 vs 19 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) and median survival (25 vs 31 vs 29 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) were similar in the three groups. MP produced a higher degree of thrombocytopenia than combination chemotherapy at standard (P = 0.002) or high dose (P = 0.01), this leading to a significantly higher dose reduction in the MP arm (P < 0.001 and P = 0.003 for VCMP/VBAP 'SD' and VCMP/VBAP 'HD', respectively). CONCLUSION: In these trials the response rate significantly correlated with the regimen intensity. However, no significant differences in response duration and survival were found. This highlights the limited role of conventional chemotherapy in MM and the need for further trials, aimed at determining the impact of new treatment approaches such as high-dose therapy/autotransplantation.

Oclusión dentaria en pacientes con Hansen

La oclusión dentaria es la posición recíproca en que quedan los dientes de arco respecto a los del otro cuando se cierran, desarrollan la mayor fueza, ejercen presión sobre los molares y quedan en posición normal los cóndilos mandibulares. En esta posición los dientes tienen el amyor número de puntos de contacto, con lo cual se produce una armonía en la masticación que, junto a la articulación temporomandibular y el sistema neuromuscular, forma el sistema estomatogmático. Todo este conjunto debe poseer un equilibrio para su correcto funcionamiento. En los pacientes con Hansen dicho equilibrio se rompe debido a la atrofia de la espina nasal la cual ocasiona la respiración bucal y crea una descompensación en el crecimiento y desarrollo muscular que afecta al sistema estomatogmático provocando graves problemas.

An in vitro comparison of hollow ground and trocar points on threaded positive-profile external skeletal fixation pins in canine cadaveric bone.

OBJECTIVE: To compare the microstructural damage created in bone by pins with lathe-cut and rolled-on threads, and to determine the peak tip temperature and damage created by positive-profile external fixator pins with either hollow ground (HG) or trocar (T) tips during insertion. STUDY DESIGN: An acute, in vitro biomechanical evaluation. SAMPLE POPULATION: Twenty-seven canine tibiae. METHODS: Lathe-cut thread design with T point (LT-T), rolled-on thread design with T point (RT-T), and rolled-on thread design with HG point (RT-HG) pins were evaluated. Twenty pins of each type were inserted under constant drilling pressure into 12 canine tibiae (12 diaphyseal and 8 metaphyseal sites per pin type). Peak pin tip temperature, drilling energy, end-insertional pin torque, and pullout force were measured for each pin. For the histologic study, five pins of each type were inserted into cortical and cancellous sites in 15 additional tibiae. Entry and exit damage, and thread quality were assessed from 100 micron histologic sections by using computer-interfaced videomicroscopy. RESULTS: T-tipped pins reached higher tip temperature in both diaphyseal and metaphyseal bone compared with HG-tipped pins. RT-T pins had higher pullout strength (diaphyseal) and end-insertional torque compared with other combinations. No differences in drilling energy or insertional bone damage was found between the three pin types (P < .05). CONCLUSIONS: T-tipped pins mechanically outperformed HG-tipped pins. Pin tip and thread design did not significantly influence the degree of insertional bone damage. CLINICAL RELEVANCE: T-tipped pins may provide the best compromise between thermal damage and interface friction for maximizing performance of threaded external fixator pins.

[Functional activity of auditory cortex studied with SPECT: methodology validation and application in bilateral profound deafness]. / Estudio de la actividad cortical auditiva mediante SPECT cerebral: validación del método y aplicación en la hipoacusia profunda bilateral.

To evaluate the differences in the functional activity of the auditory cortex between normal hearing and profound deafness, a perfusion single photon emission tomography (SPECT) study was designed. SPECT stereotaxic localisation of the auditory cortex was previously validated in 2 brains by means of an anatomical study of the macroscopic localisation and cytoarchitecture of the auditory cortex. Additionally, 15 controls with normal hearing and 30 patients with profound bilateral deafness were scanned using external anatomical point sources (glabela, ineon) for stereotaxic location of the auditory cortex. The normal controls were scanned in auditive deprivation and, in 10 cases, during a monoaural tonal stimulation. Cerebral blood flow relative to cerebellum (relCBF) was assessed in the auditory cortex. The anatomical study showed that mean differences between the true auditory cortex size and the measured SPECT value were less than 2.5 mm. Nevertheless, only the caudal aspect of this area corresponded to the primary auditory cortex in the cytoarchitectonic study. During tonal stimulation, control subjects presented a significant increase of relCBF in the auditory cortex bilaterally, with significant differences in the asymmetry index (contralateral to the side of stimulation). The relCBF in the auditory cortex of controls in deprivation conditions was significantly higher than in deaf patients. There were no significant differences between groups of deaf patients, however the highest values were seen after cochlear implant. SPECT is a suitable method for studying changes in auditory cortex activity relative to different functional conditions, with a possible role in cochlear implant candidates in predicting the future benefit of the implantation.

[Positron emission tomography with F-18-FDG: a new tool in the evaluation of patients with head and neck tumors]. / Tomografía de emisión de positrones con F-18-FDG: una nueva técnica en la evaluación de pacientes con neoplasias de cabeza y cuello.

INTRODUCTION: Positron emission tomography using fluoro-deoxyglucose (PET-FDG) imaging has been shown to be effective in detecting and staging malignancies based on tumor glucose metabolism. The aim of the study was to evaluate the use of PET-FDG for the detection of metastatic lesions as well as early recurrence in patients with head and neck tumors. MATERIAL AND METHODS: Eleven patients were examined with PET-FDG to study the reliability of PET in assessing regional nodal status and in identifying distant metastasis (group I) and 37 patients who had previously received curative treatment and who presented differential diagnostic problems were imaged to differentiate between scar and residual or recurrent cancer (group II). PET-FDG studies were compared to results of computed tomography (CT) in 35 patients, magnetic resonance imaging (MRI) in 4 patients and both techniques in 6 patients. RESULTS: All PET-FDG studies were positive in group I, while CT failed to detect metastatic lesions in three patients. In group II PET-FDG accurately detected recurrent disease in 22/25 patients, while CT/MRI were negative in 4 cases and equivocal in 6 cases. However, there was a false positive PET study with equivocal CT in a patient with local infection. CONCLUSION: PET-FDG was highly effective in detecting metastatic cervical lymph nodes in head and neck tumours. It was most helpful in differentiating residual or recurrent tumour from scar sequelae and it enhanced the diagnostic accuracy when CT and MRI were equivocal due to anatomical distortions.

Numerical Hydrodynamics in Special Relativity.

This review is concerned with a discussion of numerical methods for the solution of the equations of special relativistic hydrodynamics (SRHD). Particular emphasis is put on a comprehensive review of the application of high-resolution shock-capturing methods in SRHD. Results obtained with different numerical SRHD methods are compared, and two astrophysical applications of SRHD flows are discussed. An evaluation of the various numerical methods is given and future developments are analyzed. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.12942/lrr-1999-3.