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Adult acute myeloid leukemia (AML) is a highly heterogeneous stem cell malignancy characterized by the clonal expansion of immature myeloid precursors. AML may emerge de novo, following other hematopoietic malignancies or after cytotoxic therapy for other disorders. Here, we investigated the clonal vs reactive nature of residual maturing bone marrow cells in 59 newly diagnosed adult AML and mixed phenotype acute leukemia (MPAL) patients as assessed by interphase fluorescence in situ hybridization analysis of AML and myelodysplastic syndrome-associated cytogenetic alterations and/or the pattern of chromosome X inactivation, in females. In addition, we investigated the potential association between the degree of molecular/genetic involvement of hematopoiesis and coexistence of altered immunophenotypes by flow cytometry. Our results indicate that residual maturing neutrophils, monocytes and nucleated red cell precursors from the great majority of newly diagnosed AML and MPAL cases show a clonal pattern of involvement of residual maturing hematopoietic cells, in association with a greater number of altered immunophenotypes. These findings are consistent with the replacement of normal/reactive hematopoiesis by clonal myelopoiesis and/or erythropoiesis in most newly diagnosed AML and MPAL cases, supporting the notion that in most adults presenting with de novo AML, accumulation of blast cells could occur over a pre-existing clonal hematopoiesis. [ABSTRACT FROM AUTHOR]

The design of a national dose protocol for interventional radiology has been one of the tasks during the European SENTINEL Coordination Action. The present paper describes the pilot experience carried out in cooperation with the Spanish Society on Vascular and Interventional Radiology (SERVEI). A prospective sample of procedures was initially agreed. A common quality control of the X-ray systems was carried out, including calibration of the air kerma area product (KAP) meters. Occupational doses of the radiologists involved in the survey were also included in the survey. A total of 10 Spanish hospitals with interventional X-ray units were involved. Six hundred and sixty-four patient dose data were collected from 397 diagnostic and 267 therapeutic procedures. Occupational doses were evaluated in a sample of 635 values. The obtained KAP median/mean values (Gy·cm²) for the gathered procedures were: biliary drainage (30.6/68.9), fistulography (4.5/9.8), lower limb arteriography (52.2/60.7), hepatic chemoembolisation (175.8/218.3), iliac stent (45.9/73.2) and renal arteriography (39.1/59.8). Occupational doses (mean monthly values, in mSv) were 1.9 (over apron); 0.3 (under apron) and 4.5 (on hands). With this National experience, a protocol was agreed among the SENTINEL partners to conduct future similar surveys in other European countries. [ABSTRACT FROM AUTHOR]

The European BIOMED-1 Concerted Action was initiated in 1994 to improve and standardize the flow cytometric detection of minimal residual disease (MRD) in acute leukemia (AL). Three different protocols were defined to identify the normal subsets of B, T and myeloid cells in bone marrow (BM), and were applied to the different types of AL in order to study aberrant immunophenotypes. Using sensitive acquisition methods ('live gate') T cell subsets in normal BM could be identified with five triple-stains: CD7/CD5/CD3, CD7/CD4/CD8, CD7/CD2/CD3, CD7/CD38/CD34 and TdT/CD7/surface or cytoplasmic (cy)CD3 (antibodies conjugated with FITC/PE/PECy5 or PerCP, respectively). The identification of T cell subsets in BM allowed definition of 'empty spaces' (ie areas of flow cytometric plots where normally no cells are found). All studied T-ALL cases (n = 65) were located in 'empty spaces' and could be discriminated from normal T cells. The most informative triple staining was TdT/CD7/cyCD3, which was aberrant in 91% of T-ALL cases. In most cases, two or more aberrant patterns were found. Apparently the immunophenotypes of T-ALL differ significantly from normal BM T cells. This is mostly caused by their thymocytic origin, but also the neoplastic transformation might have affected antigen expression patterns. Application of the five proposed marker combinations in T-ALL contributes to standardized detection of MRD, since cells persistent or reappearing in the 'empty spaces' can be easily identified in follow-up BM samples during and after treatment. [ABSTRACT FROM AUTHOR]

An experimental study on rats showing the arterial lesions caused by the beams of gamma irradiation used in stereotactic radiosurgery is presented. The common carotid artery of the rat was irradiated with a single narrow-beam of gamma radiation with a maximum dose of 30 and 60 Gy. The results were evaluated at 4, 12 and 24 weeks after irradiation. Several focal changes in the arterial walls were observed in all periods of study with a predominance of hyperplastic (proliferative) alterations at doses of 30 Gy, and hyaline degeneration at doses of 60 Gy. Total occlusion was not observed in any case. In conclusion, vascular hyperplasia is more prominent with the lower doses evaluated. [ABSTRACT FROM AUTHOR]

The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 ± 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (χ², p < .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of patients, the dysfunction disappeared completely within 6 months, but 81.4% showed no improvement at all by the end of this period. Twelve of 15 patients experienced total improvement when the treatment was changed to moclobemide (450-600 mg/day), and 3 of 5 patients improved when treatment was changed to amineptine (200 mg/day). [ABSTRACT FROM AUTHOR]

We describe a patient with Creutzfeldt-Jakob disease (CJD) of the ataxic and panencephalopathic type. Postmortem examination revealed the characteristic lesions of CJD in the grey matter and profound white matter involvement was seen with immunocytochemical techniques. Ultrastructural white matter lesions were identical to those described in experimentally transmitted CJD. There was marked loss of cerebellar granule cells with virtual disappearance of parallel fibres, but Purkinje cells were only slightly reduced. Electron microscopic studies revealed extensive degenerative changes including cytoplasmic vacuoles in both cell types. Silver methods disclosed massive impregnation of white matter and striking abnormalities of Purkinje cells consisting of hypertrophy and flattening of thick dendritic branches, reduction in the number of terminal branchlets, segmentary loss of spines and polymorphic spines. These findings show the extensive involvement of all three cerebellar cortical layers and the reactive plasticity of Purkinje cells to deafferentiation. They favour the hypothesis that demyelination represents a primary lesion of the white matter. [ABSTRACT FROM AUTHOR]

AIMS--To analyze the immunophenotype of blast cells in patients with acute leukaemia after polycythemia vera, together with the most relevant clinical and haematological disease characteristics. METHODS--The immunophenotype was analysed in nine patients by immunofluorescence flow cytometry using a panel of 15 monoclonal antibodies. The DNA content of blast cells was determined using Vindelov's technique. RESULTS--The most relevant clinical and haematological disease characteristics included: the presence of enlarged spleen and liver by 56% and 67%, respectively; a moderate degree of leucocytosis with thrombocytopenia while haemoglobin was normal in 50% of patients. All patients received alkylating agents or hydroxyurea, or both. Interestingly, the chronic phase in patients receiving this latter drug was shorter. All cases showed a myeloid phenotype, four of them reactive only to early myeloid antigens (CD13/33); in the remaining cases the blast cells displayed granulomonocytic (CD14+, CD15+), erythroid (CD71 ), or megakaryocytic (CD61+, CD41+) markers. Coexpression of lymphoid related antigens (CD7, TdT, or CD19) was also detected. The morphological assessment of blast cells agreed with the immunophenotyping in five out of the nine cases. Blast cells from all six patients analysed displayed a diploid DNA content and the proportion of S-phase cells ranged from 0.4% to 4%. CONCLUSIONS--These findings suggest a pluripotential stem cell with myeloid commitment as the target cell of acute leukaemia after polycythemia vera. [ABSTRACT FROM PUBLISHER]

Natural killer (NK) and T subsets were analyzed with appropriate dual labeling by flow cytometry in peripheral blood (PB) (66 cases) and bone marrow (BM) (55 cases) from patients with de novo AML in order to determine: (a) their distribution at diagnosis, (b) the correlation between PB and BM in NK subpopulations, (c) their relationship with the clinical and hematological disease characteristics, and (d) the changes occurring upon achieving complete remission (CR). NK cells defined by the expression of CD56 in the absence of CD3 were significantly increased at diagnosis and their levels in PB correlated with those of BM. By contrast, NK subsets defined by CD16 expression (CD16+ CD2+ and CD16+ CD2- NK-cell subsets) as well as T lymphocytes with NK activity (CD56+ CD3+), although increased in PB, displayed normal levels in BM. An additional observation of interest was the expansion of an immature NK population lacking CD16 Ag expression (CD56+ CD16-). AML cases were divided into two groups according to the absolute number of NK cells in PB; patients with the highest levels showed an increased proportion of blast cells in PB (p = 0.01), monocytic subtypes (p = 0.03), and expression of CD11b, CD14, and CD4 antigens (p = 0.05). Infections at diagnosis were not related to the level of NK cells. In 19 patients who achieved complete remission the number of CD56+ CD3- cells tended to be reduced to within the normal range. Other T-cell populations, including the CD4 naive and memory cells, were also explored, their distribution being normal in the PB of AML patients. By contrast, the cytotoxic subset CD8+/CD57+ was significantly increased (p < 0.001). These data point to the existence of marked alterations of NK cells in AML patients, possibly reflecting a host-tumor immunological interaction. [ABSTRACT FROM AUTHOR]

Lidocaine (lignocaine) was given in 42 episodes of status epilepticus (SE) in 36 patients either because of limited pulmonary reserve (22 patients) or because of lack of response to diazepam (14 patients). Lidocaine (1.5-2 mg/kg) was given intravenously in two minutes. A further identical bolus was infused if no response had occurred or if seizures recurred. With the first bolus 11 episodes of SE did not stop, but 31 responded, always in less than one minute. In 19 episodes, however, this response lasted less than 30 minutes. Twelve episodes did not recur, but 30 needed a second bolus because of recurrence. Of these, 19 episodes responded at once but SE reappeared in seven. In these seven episodes the mean control time with the second dose was 102 minutes. Five of these subsequently responded to a continuous infusion of lidocaine. Eleven patients, who had not responded to the first bolus, had no response to the second. Lidocaine is a drug that may be epileptogenic at high doses. At the doses used here, however, lidocaine seems to be a rapid acting anticonvulsant, useful in the short term management of SE and may be indicated in patients in whom respiratory or consciousness depression is undesirable and in those with no response to diazepam. The absence of response to lidocaine indicates SE resistant to treatment and poor prognosis. These data show that prompt lidocaine administration may be worthwhile when management of respiratory depression is not possible. [ABSTRACT FROM AUTHOR]