Biomedical subjects
Publications and source records attributed to P Agostini.
The absolute timing of the high-harmonic attosecond pulse train with respect to the generating IR pump cycle has been measured for the first time. The attosecond pulses occur 190+/-20 as after each pump field maxima (twice per optical cycle), in agreement with the "short" quantum path of the quasiclassical model of harmonic generation.
The double ionization of argon and xenon in an intense laser field has been studied in detail using an electron-ion coincidence technique. The observed double ionization electron spectra in xenon show resonancelike structures here resolved for the first time. In argon, the featureless spectra are consistent with rescattering. This represents a clear transition in the dynamics of strong-field double ionization, analogous to the well-known transition between the tunneling and multiphoton regimes in single ionization.
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To better define the incidence and significance of cryptic chromosome lesions in acute myeloid leukemia (AML), fluorescence in situ hybridization (FISH) studies were performed in interphase cells and, when appropriate, in metaphase cells and in morphologically intact BM smears. Fifty-five adult de novo AML (group A) and 27 elderly AML or AML after myelodysplastic syndrome (AML-MDS) (group B) were tested using probes detecting the following anomalies: -5, -7, +8, deletions of 5q31, 7q31, 12p13/ETV6, 17p13/p53, 20q11. All the patients had a normal karyotype in more than 20 cells and tested negative for the common AML-associated fusion genes. No patient in group A was found to carry occult chromosome anomalies, whereas 8/27 patients in group B (P < 0.0001) showed 5q31 or 7q31 deletion (three cases each), a 17p13/p53deletion or trisomy 8 (one case each) in 33-60% interphase cells. Metaphase cells showed only one hybridization signal at 5q31 (three cases) and 7q31 (one case), whereas two normal signals at 7q31 and chromosome 8 centromeres were seen in two patients with 7q deletion and trisomy 8 in interphase cells. The majority of blast cells (76-94%) carried the chromosome anomaly in all cases; erythroid involvement in a minority of cells was seen in three patients. In group B, the presence of occult chromosome anomalies was associated with exposure to myelotoxic agents in the workplace (5/8 cases vs 3/19, P = 0.026) and with a lower complete remission rate (0/6 patients vs 7/12, P = 0.024). We arrived at the following conclusions: (1) cryptic chromosome deletions in the order of a few hundred kb magnitude may be found in a fraction of elderly AML or MDS-related AML and not in de novo adult AML with normal karyotype; (2) these chromosome lesions are usually represented by submicroscopic rearrangements; (3) they display a specific pattern of cell-lineage involvement arguing in favor of their role in the outgrowth of the leukemic blast cells; (4) they are associated with a history of exposure to myelotoxic agents in the workplace and, possibly, with resistance to induction treatment.
In principle, the temporal beating of superposed high harmonics obtained by focusing a femtosecond laser pulse in a gas jet can produce a train of very short intensity spikes, depending on the relative phases of the harmonics. We present a method to measure such phases through two-photon, two-color photoionization. We found that the harmonics are locked in phase and form a train of 250-attosecond pulses in the time domain. Harmonic generation may be a promising source for attosecond time-resolved measurements.
The double ionization of helium in the strong-field limit has been studied using an electron-ion coincidence technique. The observed double ionization electron energy spectra differ significantly from the single ionization distributions. This gives new support to the rescattering model of double ionization and explicitly reveals the role of backward electron emission following the e-2e ionizing collision.
At diagnosis, approximately half of myelodysplastic (MDS) patients presents a normal karyotype by conventional cytogenetic analysis (CCA). Fluorescent in situ hybridization (FISH) is more sensitive than CCA allowing for the detection of minor clones and of submicroscopic lesions. We have analyzed by FISH 101 MDS patients with normal karyotype for the occurrence of the abnormalities which are most frequently observed in MDS (ie -5/5q-, -7/7q-, +8, 17p-). In 18 patients, 15 to 32% of interphase cells were found to carry one FISH abnormality. Six patients presented trisomy 8, five had del(5)(q31), five del(7)(q31), one monosomy 7 and one del(17)(p13). FISH abnormalities were more frequently observed among patients with an increased percentage of bone marrow blasts (P = 0.001). FISH abnormalities were also associated with a higher rate of progression into AML (13/18 vs 12/83, P < 0.001) and were predictive for a worse prognosis (P < 0.001). Multivariate analysis indicated that FISH positivity and IPSS risk group were independent predictors for a poor survival (P = 0.0057 and 0.0123, respectively) and for leukemic transformation (P = 0.0006 and 0.035, respectively). Leukemic transformation in FISH-positive patients was associated in all cases with an expansion of the abnormal clone. Our data demonstrated that a significant proportion of MDS patients with normal karyotype presented, if analyzed by FISH, clones of cytogenetically abnormal cells which played a determinant role in the progression of the disease. The presence of FISH abnormalities identified a group of MDS patients with normal karyotype characterized by an inferior prognosis.
To better define the incidence and nature of secondary chromosome anomalies in mantle cell lymphoma (MCL) carrying the t(11:14)/BCL1 rearrangement, cytogenetic and fluorescence in situ hybridization studies (FISH) were performed in 42 patients (39 classical histology, 3 blastoid variant), using 6q21, 9p21/p16, 13q14, 17p13/p53 and chromosome-12-specific probes. Karyotypes from 89 cases published in 5 recent series including patients diagnosed in a homogeneous fashion were reviewed. In our series, FISH confirmed the interpretation of the karyotype in all cases and disclosed cryptic chromosome deletions in a sizeable fraction of cases. One patient (2.4% of total) was found with a cryptic 9p21 deletion by FISH. Two cases (4.8%) had a 6q21 deletion at CCA and at FISH; +12 was found in three cases by CCA plus nine by FISH (28.6%); 13q14 deletion was found in six cases by CCA plus 16 by FISH (52.4%), 17p13 deletion in three cases by CCA plus 8 by FISH (26.2%). In 131 patients (42 present series plus 89 in the literature) secondary chromosome aberrations seen by conventional cytogenetic analysis in more than 5 cases included deletions/translocations (del/t) 6q15-23 [15 cases]; -13 [14 cases]; del/t 1p21-31 [12 cases]; +3q [11 cases]; del/t 17p [9 cases]; 8p translocations and del(Y) [8 cases each]; -20 [7 cases]; 13q14 deletion, del/t 11q22-23, del/t 9q, del(10)(q22q24), -20, -21, -22 and -X [6 cases each]. We arrived at the following conclusions: i) though no secondary anomaly is specific for MCL, there is a distinct profile of recurrent chromosome lesions in MCL with 1p21-31 deletions, 8p translocations, 11q22-23 anomalies having a strong association with CD5+ B-cell lymphomas of low-to-intermediate grade histology; ii) FISH enabled the detection of cryptic chromosome 12, 13q and 17p rearrangements in a sizeable fraction of cases; iii) 9p21/p16 deletions did not occur at a high incidence in this series, possibly because of the low number of cases with blastoid variant.
BACKGROUND AND OBJECTIVES: To improve the definition of the incidence and significance of chromosome lesions occurring in marginal zone B-cell lymphoma (MZBCL). DESIGN AND METHODS: Fourteen cases of MZBCL diagnosed according to the REAL classification were studied by conventional chromosome analysis (CCA) and by interphase fluorescence in situ hybridization (FISH) using the following probes: 3q27/BCL6, 6q21, 7q31, 9p21/p16, 11q22/ATM, 13q14, 17p13, centromeres of #3, #7, #12. Pertinent clinical data were collected. RESULTS: Primary disease presentation consisted of histologically documented splenic MZBCL in 9 cases, nodal MZBCL in 3 cases and extra-nodal MZBCL in 2 cases. Four cases showed evolution into a high-grade lymphoma, due to the presence of a predominant large cell or blast cell component. Clonal karyotype anomalies were detected by CCA in 12 cases, 6 of which had a complex karyotype, including all 4 cases with high-grade histology. Interphase FISH confirmed cytogenetic data and revealed several cryptic chromosomal lesions. Overall, total/partial +12 was found in five cases; 13q14 and 17p13 deletion were found in four cases each; +3, 7q31 deletion and a BCL6 split signal were found in three cases; deletions at 6q21 and 11q22.3 in two cases each; +7 and a 9p21 deletion were found in one case each. INTERPRETATION AND CONCLUSIONS: i) Besides +3 and 7q-, 13q14 deletion, total/partial +12, BCL6 rearrangement, and deletions at 6q21, 11q22-23, and 17p13.3 are relatively frequent events in MZBCL; ii) unlike in mantle cell lymphoma, 9p21 deletion occurred infrequently in MZBCL; iii) a switch into high grade histology is usually associated with complex chromosome defects, including 6q-, 11q-, +12, and 17p.
BACKGROUND AND OBJECTIVES: A pluripotent progenitor cell was demonstrated to be involved in myelodysplastic syndromes (MDS) with normal karyotype or with numerical chromosome aberrations, but the pattern of lineage involvement by the 5q31 deletion in the 5q- syndrome is unknown. We performed this study in order to define the distribution pattern of the 5q- anomaly better in the non-lymphoid cell compartment DESIGN AND METHODS: Bone marrow (BM) smears from 8 patients with the 5q- syndrome were studied by a modification of the fluorescent in situ hybridization (FISH) technique that allowed direct visualization of cell morphology. A commercial LSI EGR1 probe (Vysis Inc.) for the 5q31 band was used simultaneously in dual-color experiments with a chromosome-5-centromeric probe (Vysis Inc.) on BM smears from 8 patients with the 5q-syndrome. As additional internal controls a chromosome-7-centromeric probe and a 7q31 probe were used. To establish the sensitivity limit of this approach 5 normal BM smears were studied. All 8 patients had the 5q- chromosome as the sole anomaly in 45% to 75% of the interphase cells. RESULTS: For each patient 20-40 erythroblasts were analyzed: they were mostly proerythroblasts and basophilic erythroblasts. In all patients a clone carrying the 5q31 deletion was detected (35-50% of the cells, median 45%). Between 20-50 granulocyte precursors were scored; the 5q31 deletion was found in 40%-50% (median 45%) in all cases. The proportion of neutrophils carrying the 5q deletion was consistently lower than the corresponding value in promyelocytes (28.7% vs 45.6%). In the 20-25 megakaryocytes analyzable in all patients, the overall incidence of 5q31 deletion was 52-68%. Equal proportions of large multilobular megakaryocytes and hypolobular megakaryocytes characteristic of the 5q- syndrome were scored: the latter cells showed the 5q31 deletion more frequently than the former cells (93.6% vs 19.3% of the cells). In 66% to 100% of the cases (median 83%) a few cells with uncondensed nuclear chromatin pattern, and two or three prominent nucleoli with cytoplasmatic hypogranulation were seen in each sample carrying the 5q31 deletion. INTERPRETATION AND CONCLUSIONS: We arrived at the following conclusions: i) the transformation in the 5q- syndrome involves an early progenitor cell retaining the ability to proceed along multiple differentiation pathways; ii) there is a preferential distribution of the 5q31 deletion within immature cells and morphologically abnormal megakaryocytes.
PURPOSE: To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/-) in B-cell non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22-23 probe recognizing ATM sequences. Pertinent clinical data were collected. RESULTS: A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/- patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/- more frequently had a complex karyotype (P =.01) and the AA karyotype (P =.04) compared with patients without ATM+/-. With the exception of a poor performance status (P =.001), no correlation was found between ATM+/-, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P <.0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P =.0004), along with performance status (P =.0006), serum lactate dehydrogenase level (P =.03), splenomegaly (P =.01), and histologic grade (P =.03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/- maintained its prognostic importance as an independent variable in both histologic groups (P =.0001 and P =.016, respectively). CONCLUSION: Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/- status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.
The emergency department gynaecologist is often faced with requests for emergency postcoital contraception. The physician on duty is usually very busy and does not always have enough time to perform a complete evaluation of the woman's state of health. The emergency gynaecologist who prescribes postcoital contraception also has a number of other problems to cope with in regard to the pharmacological preparations on the market, the efficacy of various methods, the monitoring of side-effects which are not, always, tolerated by all patients and the outcome of his therapeutic prescription. All these aspects should be emphasized in the "first aid" counselling offered to the patients. In conclusion, we consider that any women who decides to use postcoital contraception should have the right to receive assistance of guaranteed quality throughout the period that elapses between taking the drug and the subsequent menstrual cycle. This is not strictly guaranteed by an emergency gynaecological service.
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BACKGROUND AND OBJECTIVE: 13q14 deletion frequently occurs as a single anomaly in chronic lymphocytic leukemia (CLL) with favorable prognosis. This study was performed to assess the distribution of 13q14 deletion in non-Hodgkin's lymphoma (NHL) and to analyze its correlation with salient clinicopathologic features. DESIGN AND METHODS: One hundred and twenty-five NHL were analyzed by cytogenetics and by interphase fluorescence in situ hybridization (FISH), using a 13q14 cosmid probe recognizing DNA sequences between the Rb gene and the D13S25 marker. Clinical records all patients were surveyed. RESULTS: A 13q14 rearrangement was present in the stemline in 10 patients; 15 additional cases were shown by FISH to carry 13q14 deletion in 55-90% of the interphase cells, giving a 20% overall incidence for this anomaly. Six of 44 patients had a low-grade NHL, 14/28 had mantle cell lymphoma (MCL), 5/42 had a high grade NHL (p<0.0001). There was not correlation between 13q, karyotype status and complexity. A statistically significant association was found between 13q-, presence of splenomegaly and PB involvement, lower probability of attaining complete remission (CR) and shorter survival. These findings were not simply a function of the association of 13q- with MCL. In multivariate analysis, a complex karyotype had prognostic importance (p=0.0078), along with age (p=0.01), histology (p=0.001), LDH (p=0.03), PS (p=0.001), sex (p=0.03) and splenomegaly (p=0.02). INTERPRETATION AND CONCLUSIONS: 13q14 deletion represented an early chromosome change and showed a preferential association with MCL, though it was found in virtually all principal histologic subtypes, irrespective of clinical stage, karyotype status and complexity. Patients with 13q14 deletions had a low CR rate, suggesting that genes relevant to lymphomagenesis are located in this chromosome segment that warrants molecular cytogenetic investigation.
The aim of this report is to provide a medical form to use in case of sexual assault, prepared taking into consideration the information lacking at present in most medical reports on the subject. This call for the necessity to conform the medical approach to the same protocol which may also be used from the forensic medicine point of view. More precise information should be obtained about the assault and the injuries inflicted, and also an immediate psychological support should be given to the victim. This information will then serve as a guide to the medical staff.
To better define the role of exposure to myelotoxic agents in the genesis of myelodysplastic syndrome (MDS), we carried out (a) a case-control study for the determination of the relative risk (RR) of developing MDS, including 178 consecutive patients and 178 sex- and age-matched controls: (b) a study of clinicobiological features in MDS arising after occupational exposure to myelotoxic agents and in MDS in 'non-exposed' patients. The definition of the 'exposure' status was based on a predetermined questionnaire, with calculation of an 'exposure' index (hours/day x days/year x years). Cumulative exposure to pesticides or to organic solvents, for >2400 h, was recorded in 48 and 25 MDS patients, respectively, compared to 27 and four controls (P<0.00001; RR 3.74; 95% confidence interval 2.02-5.37). Older age and an excess of refractory anaemia with ringed sideroblasts and refractory anaemia with excess of blasts was noted among 'exposed' MDS-patients (group 1), compared to non-exposed MDS-patients (group 2). 68.3% patients in group 1 had clonal chromosome changes, compared with 43.2% patients in group 2. Complex karyotypes, -7/7q-, -5/5q-, +8, 7p and 17p aberrations were seen more frequently in group 1, whereas a normal karyotype, isolated 5q- or 20q- occurred more frequently in group 2. The association of exposure to myelotoxic agents with older age at presentation and with unfavourable chromosome changes accounted for the shorter survival observed in 'exposed' patients. These data show that occupational exposure to pesticides and organic solvents in our region resulted in an increased RR of developing MDS and that a distinct cytogenetic profile was associated with MDS in 'exposed' patients. These findings provide strong indirect evidence that these agents may play a role in the pathogenesis of MDS, preferentially targeting some of the chromosome regions which are frequently involved in therapy-related myeloid neoplasias.
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