Tonically active neurons in the primate striatum and their role in the processing of information about motivationally relevant events

Analysis of recordings of single neuronal activity in the striatum of monkeys engaged in behavioural tasks has shown that tonically active neurons (TANs) can be distinguished by their distinct spontaneous firing and functional properties. As TANs are assumed to be cholinergic interneurons, the study of their physiological characteristics allows us to gain an insight into the role of a particular type of local-circuit neuron in the processing of information at the striatal level. In monkeys performing various behavioural tasks, the change in the activity of TANs, unlike the diversity of task-related activations exhibited by the phasically active population of striatal neurons, involves a transient depression of the tonic firing related to environmental events of motivational significance. Such events include primary rewards and stimuli that have acquired a reward value during associative learning. These neurons also respond to an aversive air puff, indicating that their responsiveness is not restricted to appetitive conditions. Another striking feature of the TANs is that their responses can be modulated by predictions about stimulus timing. Temporal variations in event occurrence have been found to favour the responses of TANs, whereas the responses are diminished or abolished in the presence of external cues that predict the time at which events will occur. These data suggest that the TANs respond as do detectors of motivationally relevant events, but they also demonstrate that these neurons are influenced by predictive information based on past experience with a given temporal context. TANs represent a unique subset of striatal neurons that might serve a modulatory function, monitoring for temporal relationships between environmental events.     

中西医结合治疗急性白血病存活十年以上5例

中西医结合是提高急性白血病长期存活的有效途径。笔者采用中药与化疗相结合的方法治疗３００余例急性白血病患者中，５例存活长达１０年以上，最长１例已存活２０年，至今皆高质量健康生存。现代药理学研究表明部分中药具有良好的抗白血病作用。     

Risk Indicators: Assessment of Infancy Predictors of Pre-School Behavioural Maladjustment

The prediction of later outcome from factors present in infancy has been an ongoing concern, with difficult temperament frequently being posited as one important risk factor. Using data from a longitudinal study of a large representative sample of children, and a categorical approach to analysis, a set of infancy risk factors covering within-child, environmental and relationship variables was related to behavioural and emotional adjustment at 4-5 years. Single risk factors, including difficult temperament, resulted in only modest increases in the prevalence of later maladjustment. However, certain combinations of risk factors were associated with markedly increased prevalence rates. The results indicate the cumulative effects of risk factors, and the need to consider temperament within a contextual framework.     

Platelet tests in the prediction of myocardial infarction and ischaemic stroke: evidence from the Caerphilly Prospective Study

A platelet test that is predictive of myocardial infarction (MI) and/or stroke would enable the targeting of anti-platelet drugs towards high-risk patients. The predictive power of several platelet tests for MI and for stroke was examined in 2000 older men in the Caerphilly Cohort Study of Heart Disease, Stroke and Cognitive Decline. The tests were: aggregation to adenosine diphosphate (ADP) in platelet-rich plasma (PRP); aggregation to ADP in whole blood measured using an impedance method and a test of platelet aggregation induced in whole blood by high-shear flow. Around 200 MIs and 100 ischaemic strokes occurred during a 10-year follow-up. Neither primary nor secondary aggregation in PRP was predictive of MI. However, the fifth of men in whom the primary response to ADP was least, showed the highest risk of a subsequent stroke [relative odds (RO) 1.64; 95% confidence interval (CI) 1.12-2.43]. Aggregation in whole blood was not predictive of MI but, again, the fifth of men with the least platelet response showed the highest stroke incidence (RO 1.79; 95% CI 1.06-3.00). Retention of platelets in the high-shear test was not predictive of either event.     

Enhanced Anti-tumor Effect of Trastuzumab in Combination with Cisplatin

The oncogenenic transmembrane tyrosine kinase receptor HER–2/neu is a promising target for treatment of HER–2–overexpressing cancers. The humanized anti-HER–2/neu antibody Trastuzumab is under clinical evaluation in combination with chemotherapy against breast cancer. The combination of Trastuzumab and cisplatin is expected to be active against HER–2/neu-expressing tumors. We examined the mechanisms of this combination effect against human solid tumor cells in the presence of human peripheral blood mononuclear cells (PBMCs) using an in vitro MTT assay. The growth-inhibitory effects of cisplatin (CDDP) on the tumor cells were not significantly affected by Trastuzumab in the absence of effector cells. CDDP alone at a dose of less than 12.5 μ M did not affect the viability of PBMCs, as determined by MTT assay, suggesting that PBMCs could exert antibody-dependent cell-mediated cytotoxicity (ADCC) at this CDDP concentration. The combination of Trastuzumab and CDDP showed higher cytotoxic effects against the tumor cells in the presence of PBMCs. The CDDP concentration required to inhibit tumor cell growth by 50% was reduced to ∼20% by Trastuzumab in the presence of PBMCs at an effector/target ratio of 10. It may be important to select combined chemotherapeutic agents which do not diminish the ADCC activity of Trastuzumab via PBMCs. Both the expression of HER–2/neu and the ADCC activity may be important determinants of the therapeutic benefit of the Trastuzumab/CDDP combination.     

Complications of combined surgery and radiation therapy for carcinoma of the endometrium

Long-term gastrointestinal (GI) and urinary tract (UT) complications were evaluated in 133 women with carcinoma of the endometrium who were treated by both radiotherapy and hysterectomy. Major complications developed in 8% of patients who received external pelvic radiation but in none with intracavitary radiation. GI complications were more frequent and more severe in patients receiving external pelvic radiation than in those who received only intracavitary radiotherapy, irrespective of the sequence of treatment. UT complications were more frequent with prehysterectomy external radiotherapy (N = 39) than with posthysterectomy external radiotherapy (N = 21).     

Predicting the response to recombinant human growth hormone in Turner syndrome: KIGS models

A mathematical model for predicting the growth response in patients with Turner syndrome who received growth hormone (GH) therapy was developed by analysing data from KIGS, the Pharmacia & Upjohn International Growth Database. A Model for year 1 of GH therapy explained 46% of the variability of the growth response, with GH dose being the most important of the predictors of height velocity. In years 2-4 of therapy, height velocity during the previous year was the most important predictor, suggesting that an individual's initial response to GH may determine the height outcome of treatment. Additional treatment with oxandrolone. The predictions in all 4 years were highly accurate, as indicated by the low error SDs. However, relatively low predictive power ( R ) during years 2-4 of treatment suggests the models are missing other parameters that would explain more of the variability of the growth response. These growth prediction models could help clinicians to design individualized treatment regimens, provide realistic expectations of therapy outcomes, and adjust treatment on the basis of detected differences between observed and predicted height velocities.     

The prediction of nonresponse to pharmacotherapy in panic disorder: a review.

Several effective pharmacotherapeutic treatments exist for panic disorder; however, not all patients respond to treatment: between 20% to 40% are non‐responders. Recent studies have reported several predictors of nonresponse to pharmacotherapy. In this review two questions are addressed: is there consensus with respect to predictors of nonresponse and are there any differences between short‐term and long‐term predictors? In this review both short‐term and long‐term outcome studies are discussed. Studies were included if at least DSM‐III criteria were used and baseline variables were investigated as possible predictor of response, or nonresponse, to pharmacotherapy. Of each clinical predictor, tallies were made of the particular predictors employed and of those predictors that predicted nonresponse. It appears that a long duration of illness and severe agoraphobic avoidance are robust predictors of nonresponse, particularly in long‐term studies. Personality disorders, or even personality traits, are possibly the most robust predictors of nonresponse. Several factors appear to be robust predictors of nonresponse: factors that are present before treatment and exert their influence on short‐term and long‐term treatment outcome. Prospective studies are needed to further investigate these factors and to test whether it is viable to intervene in an attempt to increase treatment response. Depression and Anxiety 14:112–122, 2001. © 2001 Wiley‐Liss, Inc.     

Predictors of a normal chest x-ray in respiratory syncytial virus infection

Respiratory syncytial virus (RSV) accounts for the majority of lower respiratory tract infections (LRTI) in infants and young children. A chest x-ray is frequently performed in infants with LRTI caused by RSV. The aim of this study was to develop and validate a prediction model to estimate the probability for a normal chest x-ray in children with RSV infection. For this purpose, easy obtainable diagnostic parameters were used. This prediction model may be applied to decide which patients do not require a chest x-ray. The data of 287 children admitted with RSV infection or diagnosed as such in the outpatient department of the Sophia Children's Hospital between 1992-1996 were studied. The derivation set comprised 232 patients (1992-1995), and the validation set contained 55 patients (1995-1996). A chest x-ray was designated as normal when atelectasis, hyperinflation, or pulmonary infiltrates were absent. In order to develop a prediction model, patient history and clinical and laboratory variables were consecutively entered into a logistic regression model according to the diagnostic workup that was practiced at the time. Variables with P < or = 0.10 were retained in the model. The predictive accuracy of the multivariable models was examined using the area under receiver operating curve (ROC-area). In 202 (87%) patients from the derivation set, a chest x-ray was performed. A normal chest x-ray could be predicted by increasing age, increasing birth weight, presence of rhinitis, absence of retractions, and increasing arterial oxygen saturation. The ROC-area was 0.80 in the derivation and validation sets. This prediction model was transformed into a score chart. In conclusion, a normal chest x-ray can accurately be predicted, using a model including easily obtainable patient characteristics, and clinical and laboratory variables. This model may be a useful tool in deciding whether or not to perform a chest x-ray in patients with RSV infections.     

Out-patient behaviour therapy in alcoholism: impact of personality disorders and cognitive impairments

OBJECTIVE: We investigated whether alcoholic patients with comorbid personality disorders and those with cognitive impairments would benefit in a different way from different behaviour therapy strategies. METHOD: After detoxification, 120 alcoholics were assigned randomly to one of three out-patient treatment programmes comprising 'coping skills training', 'cognitive behaviour therapy' or unspecific supportive control therapy. Personality disorders and cognitive impairments were assessed at the beginning of the 6-month treatment period. RESULTS: The impact of concomitant personality disorders or cognitive impairments was generally only moderate and mainly independent from treatment condition. However, alcoholic patients relapsing within 6 months after detoxification showed a higher rate of personality disorders (especially antisocial and borderline) and slightly more cognitive deficits (especially in verbal memory and visuomotor functions) than abstainers even before therapy. CONCLUSION: The high amount of early relapses and drop-outs probably hindered larger differentiated treatment effects. Hypotheses will be retested in treatment completers using forthcoming follow-up data.