Serum tocopherols, selenium and lung cancer risk among tin miners in China

Objective: To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case–control study nested in an occupational cohort of tin miners. Methods: Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection. Results: Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008). Conclusion: Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol.     

Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in na?ve atopic asthmatic children.

BACKGROUND: Measurement of fractional exhaled nitric oxide (FENO) is a noninvasive, simple, well-tolerated, and reproducible marker of airway inflammation. Asthmatic children with normal respiratory function could be affected by airway inflammation. The aim of this study was to assess the correlation between FENO and bronchial hyperesponsiveness (BHR) to methacholine, and between FENO and lung function in atopic children with intermittent asthma. METHODS: Thirty-seven children (21 male), aged 7.2-14.4 years (median: 10.9 years), suffering from mild intermittent atopic asthma with a physician-diagnosed history of wheezing and/or chest tightness were studied. None had taken anti-asthmatic therapy for at least three months before the study. No child had symptoms of respiratory tract infection in the month before the study. All subjects underwent FENO measurement, pulmonary function testing and the methacholine provocation tests. RESULTS: The mean percentages of FEV1 and FEF25-27 were 91.9+/-10.5 and 88.3+/-11.8, respectively. The mean FENO was 62.2+/-39.2 ppb and PC20 methacholine was 0.93 mg/ml+/-0.54. Significant correlations were identified between FENO and FEV1 (p<0.0059, r=0.468) and between FENO and FEF25-75 (p<0.0098, r=0.439). There was no correlation between FENO and logPC20 (p=0.14). CONCLUSIONS: A single FENO measurement is probably of scarce prognostic and predictive value and it is not surprising to find discordance with BHR. We suggest that FENO measurement could represent a good marker of airway inflammation also in na?ve atopic children with intermittent asthma. Repeated measurements over time are probably necessary to understand better the clinical implications of the data obtained in this study.     

Assessment of motor neuron excitability in parkinsonian rigidity by the F wave

Summary F-wave responses from abductor pollicis brevis muscle occurred more frequently, with a larger amplitude and longer duration in rigid parkinsonian patients than in age-matched normal controls. F-wave potentiation during voluntary contraction was impaired in parkinsonian patients. These findings suggest that spinal motor neuron excitability is enhanced in rigidity. F-wave amplitude was significantly correlated to the clinical evaluation of motor disability, so that the F wave may be regarded as a useful approach to quantitative evaluation of rigidity.     

Pharmacokinetics of Dexamethasone and Valspodar,a P-glycoprotein (mdr1) Modulator: Implications for Coadministration

Study Objective . To assess the potential for a drug-drug interaction between valspodar, a P-glycoprotein (mdr1) modulator used as a chemotherapy adjunct, and dexamethasone, widely included in oncology antiemetic regimens. Design . Randomized, open-label, three-period crossover study. Setting . Clinical pharmacology research center. Subjects . Eighteen healthy men volunteers (age 25.8 ± 3.5 yrs, weight 71.6 ± 10.3 kg). Interventions . Subjects received single fasting oral doses of valspodar 400 mg, dexamethasone 8 mg, and both drugs concomitantly with 2- to 3-week washout phases between administrations. Measurements and Main Results . Lack of a pharmacokinetic drug-drug interaction with respect to valspodar was conclusively demonstrated for both C_max,b (2.3 ± 0.4 vs 2.4 ± 0.5 μg/ml) and AUC_b (19.8 ± 4.8 vs 19.6 ± 4.9 μg·hr/ml) inasmuch as bioequivalence criteria were satisfied when comparing administration alone with coadministration, respectively. Although no changes in the rate of dexamethasone absorption were noted on coadministration with valspodar (C_max 88 ± 23 vs 91 ± 20 ng/ml), overall exposure was significantly increased by 24% on average (AUC 400 ± 87 vs 494 ± 90 ng·hr/ml). Regression analysis of valspodar C_max,b and AUC_b during coadministration versus the extent of the interaction (percentage increase in dexamethasone AUC) did not reveal a concentration-effect relationship (p=0.7299 and 0.9718, respectively). Conclusion . Given dexamethasone's wide therapeutic index and the short duration of coadministration foreseen for these drugs in a clinical setting (maximum 1 wk/chemotherapy cycle), the 24% increase in dexamethasone's AUC is unlikely to be relevant. Thus no alterations in valspodar or dexamethasone dosages appear warranted when the two drugs are coadministered. Multiple-dose experience in patients would be desirable to confirm these conclusions.     

Early-onset ataxia with cardiomyopathy and retained tendon reflexes maps to the friedreich's ataxia locus on chromosome 9q

Absence of lower limb tendon reflexes has been considered an essential diagnostic criterion for Friedreich's ataxia (FA). However, preservation of knee and ankle jerks has been reported in a few patients. Linkage analysis to FA locus (FRDA) on chromosome 9q13-21.1 was performed in 11 patients from 6 families with FA phenotype, including cardiomyopathy, but retained reflexes (FARR). A maximal lod score of 3.38 at recombination fraction theta equal to 0.00 was obtained demonstrating that FARR maps to the FRDA locus. These results suggest that FARR is a variant phenotype of FA.     

Neuroanatomical and neurocognitive differences in a pair of monozygous twins discordant for strictly defined autism

In this study, we investigated the neuroanatomical similarities and differences between a pair of monozygotic, 7.5-year-old twin boys discordant for strictly defined autism, to identify neuroanatomical pathways that are impaired in individuals with autism. Although the unaffected twin did not fulfill the traditional diagnostic criteria for autism, he displayed constrictions in social interaction and play that were consistent with the broader phenotype for autism that has been described in nonautistic co-twins. Magnetic resonance imaging scans were obtained for each brother and compared with the scans of 5 age- and sex-matched unaffected peers. Quantitative analysis of brain anatomy revealed that the affected twin had markedly smaller caudate, amygdaloid, and hippocampal volumes, and smaller cerebellar vermis lobules VI and VII, in comparison with his brother. Both twins evidenced disproportionately reduced volumes of the superior temporal gyrus and the frontal lobe relative to the comparison sample. The results suggest the dysfunction of two separate but overlapping neuroanatomical pathways, ie, one subcortical network differentiating the twins from each other that may underlie the traditional neurobehavioral phenotype for strictly defined autism, and a second cortical network differentiating the twins from the comparison sample that may lead to the broader phenotype for autism.     

New subcortical components of the cerebral somatosensory evoked potential in man

Two new components of the human SEP upon stimulation of the contralateral median nerve at the wrist have been identified. Such components have been called N₁₆ and N₁₇, according to their polarity and latency. N₁₆ and N₁₇, as well as the N₁₄-P₁₅ complex, are generated by separate subcortical dipoles. Particularly, they are supposed to be far-field reflections of the activity of the dorsal columns nuclei or the medial lemniscus (N₁₄-P₁₅), the thalamus (N₁₆) and the thalamo-cortical radiation (N₁₇). Moreover, it has been established that N₁₄ is the very first intracranial component of the human SEP, the main peak of S wave and the preceding ones being extracranial in origin.
A new classification of SEP intracranial components including early (N₁₄ through N₁₇), intermediate (N₂₀ through P₃₀) and late events is proposed.     

Mazindol and amphetamine as inhibitors of the uptake and releasers of 3H-dopamine by rat striatal synaptosomes

Summary The effects of mazindol, amphetamine and fentluramine on uptake and release of ³H-DA by synaptosomes were studied in different systems.In in vitro incubations of ³H-DA with synaptosomes isolated from the caudate nucleus of the rat, mazindol inhibited the uptake of the radioactivity more potently than did amphetamine.When the synaptosomes were isolated from the caudate nuclei of rats treated in vivo with either mazindol or amphetamine, the uptake of ³H-DA during in vitro incubation was lower with synaptosomes of amphetamine-treated rats than with those of mazindol-treated rats.When synaptosomes of untreated rats were prelabelled with ³H-DA and incubated in the presence of amphetamine or of mazindol, amphetamine caused a greater releaseoof radioactivity than did mazindol.Fenfluramine was without activity in all these systems.In spite of the quantitative differences, both amphetamine and mazindol appear to have similar effects on uptake and release of dopamine, and this may account for their analogous pharmacological profile.Supported by C.N.R. grant N. 75.00620.04.115.2380