Clinical characteristics and factors predicting evolution of asymptomatic IgM monoclonal gammopathies and IgM-related disorders.

We evaluated the prognostic features of 384 asymptomatic IgM-monoclonal gammopathies (aIgM-MGs) and 74 IgM-related disorders (IgM-RDs), two clinically distinct groups as proposed by the Second International Workshop on Waldenstr?m's Macroglobulinemia (WM). The cumulative probability of evolution to lymphoid malignancy at 5 and 10 years was 8% (95% CI, 5-13%) and 29% (95% CI, 21-38%), respectively, in aIgM-MGs; it was 9% (95% CI, 4-20%) and 16% (95% CI, 7-31%), respectively, in IgM-RDs (P=0.26). At a median follow-up of 45 months (12-233), 45 aIgM-MGs (11.7%) evolved to symptomatic WM (n=41), non-Hodgkin's lymphoma (NHL) (n=2), IgM multiple myeloma (n=1), and primary amyloidosis (n=1). At a median follow-up of 60 months (13-195), seven IgM-RDs (9.5%) evolved to symptomatic WM (n=6), and B-chronic lymphocytic leukaemia (n=1). At univariate analysis, in aIgM-MGs bone marrow lymphoplasmacytic infiltration, high erythrocyte sedimentation rate (ESR), haemoglobin level, IgM size, and lymphocytosis significantly correlated with evolution probability. At multivariate analysis, the latter two parameters strongly correlated with prognosis, haemoglobin being associated with a trend for a higher progression risk. In IgM-RDs IgM size, neutropenia, lymphocytosis, detectable Bence Jones proteinuria, and high ESR were associated with evolution probability. In conclusion, asymptomatic IgM-MGs and IgM-RDs are distinct clinical entities with similar probability of transformation to lymphoid malignancy.     

Quality control in the conservative treatment of breast cancer: patient dosimetry using silicon detectors.

Twenty patients with early breast cancer were treated with external irradiation, delivered with two tangential beams (6 MV X-rays) using a half-beam block (HBB) and 3-D compensating filters. All patients were immobilized with individualized cellulose acetate casts. Patient dosimetry was performed using p-type silicon detectors. Midline doses were calculated by combined entrance and exit dose measurements. The mean ratio of the measured and the prescribed doses was 96.6 +/- 3.8% at the reference point, 96.8 +/- 4.3% at off-axis points on the central plane and 96.8 +/- 7.6% at off-plane points.     

T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content

PURPOSE: To investigate the potential of magnetic resonance imaging for identification and quantification of brain iron in healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy. MATERIALS AND METHODS: Forty-nine subjects were studied at 1.5 T. Regional T1 and T2 values were compared among groups and also with histopathologic estimates of iron concentration. RESULTS: In healthy subjects, interregional T1 and T2 differences in the cortex and basal ganglia showed a good correlation with reported values for iron concentration, and intraregional variations were generally consistent with reported variability of iron concentration. Patients with multiple system atrophy had T1 and T2 shortening in the globus pallidus consistent with reported increases in ferritin-bound iron and changes in the putamen consistent with accumulation of hemosiderin (posterior portion) and neuromelanin (remainder). Both groups of patients had changes in the cortex that are consistent with decreased ferritin concentration and T2 changes in white matter consistent with demyelination. Patients with Parkinson disease also had a (nonsignificant) T2 shortening in the substantia nigra that was suggestive of iron accumulation. CONCLUSION: Most of the T1 and T2 findings appear to be related to changes in iron content and form and may possibly be used as indicators of such changes.     

Biochemical and physiological aspects of 2,5-hexanedione: endogenous or exogenous product?

Summary This article reports results regarding two different physiological aspects of 2,5-hexanedione (2,5-HD). The first is the relationship between free 2,5-HD (the fraction of real 2,5-HD) and total 2,5-HD (2,5-HD obtained from acid hydrolysis) in urine and blood of workers exposed ton-hexane. The second part of the study is an attempt to clarify physiological excretion of 2,5-HD in subjects not occupationally exposed ton-hexane. The concentration of free 2,5-HD in urine of workers exposed ton-hexane is about 8% of total urinary 2,5-HD. In blood, free 2,5-HD is about 50% of the total. The serum concentration range of total and free 2,5-HD in workers from whom blood was taken was 33–418 g/l and 14–283 g/l respectively. In subjects not exposed ton-hexane, urinary concentration of 2,5-HD ranged between 0.17 and 0.98 mg/1, the urinary excretion rate between 0.23 and 0.57g/min, and renal clearance between 14 and 66 ml/min. The blood concentration of 2,5-HD in nonexposed subjects was 6–30g/1. Fluctuations typical of a circadian rhythm were not observed for 2,5-HD in blood or urine. We think that 2,5-HD is mainly a product of intermediate metabolism in the human body. Only a minimal part could derive fromn-hexane as a ubiquitous micropollutant.     

Is underweightness still a major problem in Parkinson's disease patients?

OBJECTIVE: To evaluate the current rate of underweightness amongst Parkinson's disease (PD) patients at an Italian referral centre. DESIGN: Epidemiological study on consecutive patients presenting for the first time in a 16-month period. SETTING: Nutritional service of PD referral centre in Milan, Italy. SUBJECTS: Three-hundred and sixty-four PD patients diagnosed according to CAPIT criteria. METHODS: Anthropometric assessments: BMI and waist-to-hip ratio; evaluation of therapeutic physical activity (h/week). RESULTS: Three-hundred and sixty-four patients were included (180 female, 184 male), mean (s.d.) age 65.9 (8.9) y, mean (s.d.) duration of PD 10.6 (5.3) y; 134 patients (37%) were overweight and 92 (25%) were obese; 11 (3%) were underweight; 127 (35%) had normal BMI. No important differences in BMI according to sex and smoking status were observed. There was highly significant inverse correlation between duration of disease and BMI (P<0.001): mean (s.d.) duration of disease was 9.7 (4.7) y in overweight+obese patients, 11.1 (5.5) y in patients with normal BMI and 14.1 (7.2) y in underweight patients (P=0.0059). The waist-to-hip ratio was a cardiovascular risk factor in 47.7% of men and 73.8% of women. Mean (s.d.) therapeutic physical activity was 1.07 (1.59) h/week in overweight and obese patients vs 1.61 (2.04) h/week in patients with normal BMI (50.5% increase; P=0.03). CONCLUSIONS: At present underweightness is uncommon in PD patients in Italy; this may be due to the increase in the prevalence of overweightness in the Italian population and to modern antiparkinsonian therapy.     

Effects of the brominated flame retardant tetrabromobisphenol-A (TBBPA) on cell signaling and function of Mytilus hemocytes: involvement of MAP kinases and protein kinase C

Brominated flame retardants (BFRs) are a large group of compounds added to or applied as a treatment to polymeric materials to prevent fires. Tetrabisphenol A (TBBPA) is the most important individual BFR used in industry. Although TBBPA and its derivatives can be found in environmental samples, data are very limited on the presence of this compound in biota. Research on mammals indicates that TBBPA has low toxicity in vivo; however, in vitro TBBPA can act as a cytotoxicant, neurotoxicant, immunotoxicant, thyroid hormone agonist and has a weak estrogenic activity; in particular, the effects of TBBPA have been recently ascribed to its interactions with cellular signaling pathways, in particular with mitogen activated protein kinases (MAPKs). TBBPA has high acute toxicity to aquatic organisms, such as algae, molluscs, crustaceans and fish; however, little is known on the mechanisms of action of this compound in the cells of aquatic species. In this work, we investigated the possible effects and mechanisms of action of TBBPA on the immune cells, the hemocytes, of the marine mussel Mytilus galloprovincialis. The results demonstrate that TBBPA in the low micromolar range induces hemocyte lysosomal membrane destabilization. The effect was reduced or prevented by hemocyte pre-treatment by specific inhibitors of MAPKs and of protein kinase C (PKC). TBBPA stimulated phosphorylation of MAPK members and PKC, as evaluated by electrophoresis and Western blotting with anti-phospho-antibodies, although to a different extent and with distinct time-courses. A rapid (from 5 min) and transient increase in phosphoryation of the stress-activated JNK MAPKs and of PKC was observed, followed by a later increase (at 30-60 min) in phosphorylation of extracellularly regulated MAPKs (ERK2 MAPK) and of the stress-activated p38 MAPK. TBBPA significantly stimulated the hemocyte microbicidal activity towards E. coli, lysosomal enzyme release, phagocytic activity and extracellular superoxide (O2-) production. The results demonstrate that TBBPA in vitro activates the immune function of mussel hemocytes through kinase-mediated cell signaling and that common transduction pathways are involved in mediating the effects of this BFR in mammalian and aquatic invertebrate cells.     

Tolerability of paroxetine in Parkinson's disease: a prospective study.

Depression is a common finding in patients with Parkinson's disease (PD). Traditionally, depression has been treated with tricyclic antidepressants, which are often associated with undesirable side effects that may limit their use in PD. Few studies have been performed with selective serotonin reuptake inhibitors (SSRIs) in these patients. We assessed the tolerability of the SSRI antidepressant paroxetine (10-20 mg once per day) in 65 outpatients with PD and depression for a period of at least 3 months. Treatment was continued for 125.3+/-89.6 days (mean +/- standard deviation) in 52 patients. In these subjects the Hamilton Disease Rating Scale improved from 21.7+/-6.4 to 13.8+/-5.8 (p <0.001). Overall, 13 patients stopped paroxetine after 9.6+/-10.6 days because of adverse reactions. Two patients reported increased "off" time and tremor that reversed after treatment was stopped. No risk factors for intolerance were identified. Paroxetine is a safe and effective drug to treat depression in PD.