AML transformation in 56 patients with Ph− MPD in two well defined populations

The Philadelphia chromosome‐negative (Ph?) chronic myeloproliferative disorders (MPD) have an inherent tendency for transformation into acute myelogenous leukaemia (AML). The long‐term rate of leukaemic transformation in unselected MPD patients was studied in well‐defined MPD populations in Gothenburg, Sweden and the Côte d′Or area, Burgundy, France, respectively. Over a median observation time of 15 yr, 56 subjects (7%) out of a total of 795 patients with Ph? MPD transformed to AML. The yearly incidence of AML transformation was 0.38% in polycythaemia vera (PV), 0.37% in essential thrombocythaemia (ET) and 1.09% in idiopathic myelofibrosis (IMF). The incidence of AML development was significantly higher in IMF as compared with both PV and ET (P = 0.002 and P = 0.02, respectively). Six of the patients who developed AML had never been treated with cytoreductive agents and two had only been exposed to interferon. In IMF, the average time from diagnosis to AML transformation was 42 ± 33 months, which was significantly shorter than for both PV and ET (88 ± 56 and 76 ± 57 months; P = 0.0075 and P = 0.027, respectively). The time from diagnosis to AML transformation appears to be a continuous event as regards all three MPD entities. It was shown that 17 out of the 18 patients with PV who developed AML were females; this was true despite the fact that the male/female ratio for the whole PV group was 146/171 (0.85). As regards ET and IMF patients who transformed to AML, the gender ratio showed slight male predominance (1.33 and 1.13, respectively). The average survival time for the 56 MPD patients who developed AML was 4.6 ± 5.5 (range 0–28) months and did not differ with respect to the three subtypes of pre‐AML MPD.     

Case-control study of lymphoid neoplasm in three French areas: description, alcohol and tobacco consumption.

A multi-centre hospital-based case-control study was conducted in three regions of France between 2000 and 2003 in order to establish the risk factors of lymphoid neoplasms. We report here results concerning alcohol and tobacco consumption. A total of 298 cases and 276 controls, case-matched by inclusion centre, age and sex were included. Cases were classified according to the World Health Organization classification and validated by an expert panel of eight pathologists. Overall alcohol intake did not incur any risk increase for non-Hodgkin's lymphoma. Wine consumption marginally increased the risk of follicular lymphoma [odds ratio=2.19 (0.83-5.80)], with a higher risk for drinkers who started before the age of 20 years [odds ratio=4.04 (1.19-13.76)] and for drinkers who consumed more than 19 g of alcohol per day [odds ratio=4.37 (1.04-18.45)]. Beer and spirit consumption was not linked to non-Hodgkin's lymphoma risk. Tobacco consumption did not show a risk increase. The risk increase of follicular lymphoma due to wine consumption was new. We discuss this risk based on the French context, France being the European country with the highest alcohol consumption, particularly of wine.     

Longitudinal evaluations of psychological distress in parents of children with malignancies

The authors evaluated the psychological distress in 41 parents of children with acute lymphocytic leukaemia or with Hodgkin's disease using the Symptom Distress Checklist (SCL-90). The subjects were tested three times: within the first few days after the child's admission to hospital and 8 months and 20 months later. The experimental population was compared with a control group of 25 subjects matched for age, sex, marital status and social class. At the first evaluation the experimental group had higher mean scores than the controls for obsession, depression, anxiety and sleep disturbances. Seventy-eight % of the subjects (65.8% excluding the sleep disturbances (SlDi) subscale) scored moderate distress on at least one of the SCL-90 subscales. The 8 month and 20 month follow-ups confirmed the presence of high scores of psychological distress particularly in the sleep disturbances and depression subscales, with 78% (58.4% excluding SlDi) and 82.3% (70% excluding SlDi) of the subjects gaining scores of moderate distress in at least one of the subscales of the SCL-90.     

Randomized Multicentric Italian Study on two Treatment Regimens for Marrow Relapse in Childhood Acute Lymphoblastic Leukemia

This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluahle patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.     

Importance of entero-salivary recirculation in paracetamol pharmacokinetics

The contribution of an entero-salivary recirculation (salivary secretion-swallowed-reabsorption of drug from the gastrointestinal tract) to the values of the pharmacokinetic parameters of paracetamol was studied in a two-way crossover design. Five healthy volunteers took a tablet of Paracetamol (500 mg) in two occasions separated by a washout period. The difference between the two treatments consisted of saliva that was allowed or not to be swallowed during the 4 h of study. No statistically significant differences were found in the values of the pharmacokinetic parameters between treatments. The half-life time calculated from salivary levels was similar to the values previously reported by other authors. The percent of the oral dose excreted in saliva during 4 h of study was very low (0.1%). Secondary peaks appeared in 8 of 10 profiles. The lack of influence of salivary secretion on the pharmacokinetic parameters of Paracetamol and the low percent secreted in this fluid suggests that entero-salivary recirculation is a possible physiological phenomenon undergoing after oral administration, but it is not one of the principal phenomenon that defines the pharmacokinetic of the drug. We confirm that working with salivary samples in pharmacokinetic studies of paracetamol is a useful tool.     

The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations

Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric syndrome, affecting human infants and adolescents. Two main behavioural features are reported: (1). impaired attention and (2). an impulsive-hyperactive behavioural trait. The latter has been studied in a series of experiments, using the spontaneously hypertensive-rat (SHR) strain (which is regarded as a validated animal model for ADHD) in operant tasks. Food-restricted SHRs and their Wistar-Kyoto (WKY) controls were tested during adolescence (i.e. post-natal days 30-45), in operant chambers provided with two nose-poking holes. Nose-poking in one hole (H1) resulted in the immediate delivery of a small amount of food, whereas nose-poking in the other hole (H5) delivered a larger amount of food after a delay, which was increased progressively each day (0-100 s). As expected, all animals showed a shift in preference from the large (H5) to the immediate (H1) reinforcer as the delay length increased. Impulsivity can be measured by the steepness of this preference-delay curve. The two strains differed in home-cage circadian activity, SHRs being more active than WKYs at several time-points. During the test for impulsivity, inter-individual differences were completely absent in the WKY strain, whereas a huge inter-individual variability was evident for SHRs. On the basis of the median value of average hole-preference, we found an 'impulsive' SHR subgroup, with a very quick shift towards the H1 hole, and a flat-slope ('non-impulsive') SHR subgroup, with little or no shift. The impulsive subpopulation also presented reduced noradrenaline levels in both cingulated and medial-frontal cortex, as well as reduced serotonin turnover in the latter. Also, cannabinoid CB1 receptor density resulted significantly lower in the prefrontal cortex of impulsive SHRs, when compared to both the non-impulsive subgroup and control WKYs. Interestingly, acute administration of a cannabinoid agonist (WIN 55,212, 2 mg/kg s.c.) normalized the impulsive behavioural profile, without any effect on WKY rats. Thus, two distinct subpopulations, differing for impulsive behaviour and specific neurochemical parameters, were evidenced within adolescent SHRs. These results support the notion that a reduced cortical density of cannabinoid CB1 receptors is associated with enhanced impulsivity. This behavioural trait can be positively modulated by administration of a cannabinoid agonist. Present results confirm and extend previous literature, indicating that adolescent SHRs represent a suitable animal model for the preclinical investigation of the early-onset ADHD syndrome.