Increased aneusomy and long arm deletion of chromosomes 5 and 7 in the lymphocytes of Chinese workers exposed to benzene

Two of the most common cytogenetic changes in therapy- and chemical- related leukemia are the loss and long (q) arm deletion of chromosomes 5 and 7. The detection of these aberrations in lymphocytes of individuals exposed to potential leukemogens may serve as useful biomarkers of increased leukemia risk. We have used a novel fluorescence in situ hybridization (FISH) procedure to determine if specific aberrations in chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of workers exposed to benzene. Forty-three healthy workers exposed to a wide range of benzene concentrations (median 31 p.p.m., 8 h time-weighted average) and 44 unexposed controls from Shanghai were studied. Whole blood was cultured and metaphase spreads were harvested at 72 h. Benzene exposure was associated with increases in the rates of monosomy 5 and 7 but not monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and with increases in trisomy and tetrasomy frequencies of all three chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the exposed workers. These results demonstrate that leukemia-specific changes in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of otherwise healthy benzene-exposed workers. We suggest that aberrations in chromosomes 5 and 7 may be useful biomarkers of early biological effect for benzene exposure.      

新生儿复苏培训项目十年回顾

每年约2000万新生儿出生的中国，鼓励一对夫妻只生一个孩子，随着国民经济迅速发展，生活水平不断提高，每一个新生儿的健康都受到家庭及社会的高度关注。1991年中国要儿死亡率为50．2‰，1998年降至33．3‰，地区性差别很大，贫困地区最高可达56‰，一些条件较好的城市低至7．5‰。围产医学界公认围产窒息为要儿患病及死亡的首要原因，如合并早产、严重肺、脑疾病等后果更为严重。     

Plasma [met]enkephalin concentrations after endocrine and pharmacological modifications

Plasma [met]enkephalin was evaluated in rats either after the ablation of endocrine organs or after pharmacological modulation of the catecholaminergic and/or indoleaminergic systems. Plasma concentrations of [met]enkephalin were greatly increased after adrenalectomy both in normal and hypophysectomized rats, while there were not significant differences between female and male rats or after gonadectomy or hypophysectomy alone. Moreover, [met]enkephalin plasma concentrations were significantly decreased in rats treated with drug affecting the serotoninergic system such as reserpine, 5,7-dihydroxytryptamine or parachlorophenylalanine, while depletion of the catecholaminergic system by alfa-methyl-thyrosine did not affect the concentrations of the peptide.     

A role for serotonin and beta-endorphin in the analgesia induced by some tricyclic antidepressant drugs

The analgesic effect of acute or chronic nortriptyline, amitriptyline and their effects on morphine induced analgesia were evaluated in the rat. Clomipramine and amitriptyline, but not Nortriptyline, induce analgesia, while all potentiate the effect of morphine when administered acutely. The analgesic effect of clomipramine is blunted by both the serotonin antagonist metergoline and the opiate receptor blocker naloxone, thus indicating an involvement of both the serotoninergic and endogenous opioid system. The involvement of the serotoninergic system is confirmed by the similar results obtained with the serotonin precursor 5-hydroxytryptophan administered alone or together with morphine. A relation between the serotoninergic and the endogenous opioid systems is also shown by the increase in hypothalamic beta-endorphin concentrations elicited by all the drugs used after acute or chronic treatment, with the only exception of nortriptyline, that has been shown to exert its effects mainly through the noradrenergic system. In conclusion, the analgesic effect of clomipramine and amitriptyline and their potentiation of morphine induced analgesia seems to be related to an activation of the endogenous opioid system mediated by serotonin.     

Cerebrovascular responses to somatomotor stimulation in Parkinson’s disease: A multivariate analysis

Parkinson’s disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients.55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO₂ (EtCO₂; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO₂ and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation.Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.     

美国教学医院教师专业发展的全国性调查

在当前医学教育持续变革的背景中,医学教师的专业发展成为广泛关注的焦点.为了解目前美国以提高教师的教学技能为目标的教师专业发展(faculty development,FD)活动的参与率、课程设计、教学方法和评估策略等情况,美国约翰·霍普金斯大学预防、流行病学和临床研究中心采取邮件调查的方式,对美国277家教学医院进行了调查.     

Interleukin-2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients: II. Feasibility of LAK generation in children with active disease and in remission

Activation and expansion in culture with rIL-2 of peripheral blood (PB) and/or bone marrow (BM) specimens derived from children with ALL and ANLL, with active disease (AP) and in remission were studied (RP). Baseline NK cytolytic activity from AP was found to be depressed, whereas RP-derived cells had normal NK activity, as assayed against K562 targets. Culture in rIL-2 significantly enhanced the NK activity of both AP- and RP-derived cells and generated LAK activity, as assayed by 4-hour 51Cr release, against NK-resistant Raji cell line and against fresh, allogeneic, and autologous tumor cells. Lytic activity against fresh, cryopreserved leukemia blasts was of lower than that found against cell lines. In three patients higher lytic activity against autologous than against allogeneic blasts was demonstrated. Expansion in culture with rIL-2 varied from twofold to 120-fold. rIL-2 activation and expansion was better in RP than in AP. The predominant phenotype of activated cells, as determined by flow cytometry, was [mean % (SD)]: CD3- = 54 (12), CD8+ = 55 (17), and NKH1+ = 26 (7). The consistently high level of CD8+ cells was accompanied by very low levels of CD4+ cells: mean = 11% (14). Double-marker analysis showed mean of 33% (10) for CD3+/NKH1+ cells and mean = 32 (11) for CD8+/NKH1+ cells, implying that these populations were overlapping. Kinetics of expression of cell surface markers during 2 to 3 weeks in culture showed that CD8+ and NKH1+ enrichment occurred during the first week and lasted for up to 4 weeks, whereas CD4+ expression decreased after the second week. A significant decrease in the expression of IL-2 receptors (CD25) was observed from the second week of culture. This study shows the feasibility of in vitro generation of killer cells from PB and BM of pediatric leukemia patients.     

Altered growth hormone and prolactin responses to dopaminergic stimulation in Huntington's chorea.

Seven patients affected by Huntington's chorea were given an acute administration of 2-Br-alpha-ergocryptine (CB 154, Sandoz), a direct agonist at dopamine receptor sites. Seven nonobese hospitalized patients were used as controls. Oral administration of CB 154 (2.5 mg) induced a more prompt and consistent rise in plasma growth hormone (GH) levels in patients than in controls. GH levels rose from baseline values of 0.3+/-0.1 ng/ml to mean peak values of 20.4+/-5.1 ng/ml (120-270 min) in choreic subjects and from baseline values of 1.0+/-0.4 ng/ml to mean peak values of 5.7+/-1.6 ng/ml (180-300 min) in control subjects (P less than 0.02). Baseline plasma prolactin (PRL) values were significantly higher in choreic than in control subjects (22.1+/-6.6 ng/ml vs. 8.1+/-1.4 ng/ml, respectively, P less than 0.02); administration of CB 154 induced a more consistent PRL decrease in control than in choreic subjects. Collectively, these results suggest the existence of an abnormal regulation of GH and PRL secretion in Huntington's chorea, probably due to alterations in central dopaminergic neurotransmission.     

Immunologic status of hemophilia patients treated with cryoprecipitate or lyophilized concentrate

We evaluated 37 patients with moderate or severe hemophilia A and six patients with severe factor IX deficiency for clinical or laboratory evidence of immune abnormalities. Patients were assigned to one of four groups according to the type of clotting factor replacement. Twenty patients had received only cryoprecipitate during the two years preceding the evaluation (group I); 11 additional patients were treated predominantly with cryoprecipitate but had also received up to nine bottles of factor VIII concentrate (group II); six patients received factor VIII concentrate (group III); six patients received factor IX concentrate (group IV). There was no clinical or laboratory evidence of immunodeficiency among the 43 patients. The mean absolute number of Th cells was normal in all patient groups, but the mean absolute number of Ts cells was increased compared with controls, both in patients treated with cryoprecipitate and in patients treated with factor VIII or factor IX concentrate. There was no correlation between the Th/Ts ratio and patient age, alanine aminotransferase level, hepatitis serology, in vitro lymphocyte function, or amount of clotting factor administered. Our observations demonstrate that the volunteer or commercial origin of clotting factor replacement cannot fully explain the alterations in lymphocyte subset distribution previously described in patients with hemophilia A.