Local pharmacological manipulations of prefrontal dopamine affect conflict behaviour in rats

Several lines of research have implicated the prefrontal cortex (PFC) and its dopaminergic (DA) innervation in an animal's response to stress and anxiety. To extend these findings we evaluated the effects of bilateral infusions of DA drugs into the medial PFC of rats, in a modified conflict test, consisting of Reward, Conflict and Time-out components. In experiment 1, the effects of infusions of the DA receptor agonist apomorphine (APO) were compared to the effects of systemic injections of the same drug. APO infusions induced a dose-dependent decrease of responding in the Conflict component, indicative of an anxiogenic-like effect. However, response rates in the Reward component were simultaneously decreased, casting some doubt on the specificity of the effect. In comparison, i.p injections of APO in a second group of animals did not affect responding in the Conflict component, but dose-dependently decreased response rates during Time-out and Reward components. In experiment 2, we evaluated the effects of infusions of APO and the DA receptor antagonist cis-flupenthixol (FLU) into the medial PFC in the conflict test, and in one of its variants, the extinction of conflict test. Although both APO and FLU decreased response rates during Reward components, responding in the Conflict components of both tests was differentially affected. APO infusions decreased Conflict responses, the effect being more pronounced in the extinction of conflict test. In contrast, infusions of FLU increased responding in the Conflict components. The respective pro- and anti-conflict effects of APO and FLU infusions are in favour of a direct involvement of prefrontal DA in anxiety-related behavioural responses.     

Epidemiology of lyme disease in France: Lyme borreliosis in the region of Berry sud: A six year retrospective

The purpose of this epidemiologic retrospective is to recognize the endemic nature of Lyme borreliosis in Berry, region of France. Fifty-nine cases have been reported here during the past six years (1988–1994). An erythema migrans (EM), or a late manifestation concurrent with positive ELISA-test represents the main inclusion criterion (case definition used by the CDC). The results reveal a high incidence considering the limited information available in France. The farmer has been found to be mainly at risk, with EM being observed in 49% of cases. In general, late manifestations are rarely described. Peripheral neurological manifestations occur more frequently than those reported in the USA. The steps taken as a result of our study of Lyme disease are in accordance with the recommendations of the World Health Organization.Participants in this survey: GEEP, Groupe d'Etudes Epidémiologiques et Prophylactiques, Centre Hospitalier Intercommunal de Villeneuve Saint Georges, France; and ORMAT, Observatoire Rural des Maladies Transmissibles, Antenne du GEEP, Centre Hospitalier de La Châtre, France}     

Relations over time between psychiatric and somatic disorders: the Stirling County Study.

A longitudinal study of a general population in Atlantic Canada provided information on associations between two broad categories of illness: somatic disorders and disorders involving depression and/or anxiety. Prevalence was investigated in a sample of 1,003 adults selected in 1952 and another sample of 1,094 adults selected in 1970. Using a cohort of 618 survivors from the 1952 sample who were followed up in 1968, the authors studied prevalence at the beginning and end of the 16-year period. Incidence was also investigated so that the strength of associations between prior illness of one type and subsequent illness of the other type could be assessed. Data were obtained by interviewing subjects with the same structured schedule at each time of investigation. In prevalence enumerations, psychiatric disorders were found to be significantly associated with somatic disorders. Prior somatic disorder was significantly associated with subsequent incidence of depression and/or anxiety and vice versa. The results did not, however, show one direction of influence ("psyche-to-soma" or "soma-to-psyche") to be markedly stronger than the other. The results mainly support the concept of "generalized vulnerability" and draw attention to the importance of recognizing comorbidity in diagnosis and clinical practice.     

Localized pelvic neuroblastoma: excellent survival and low morbidity with tailored therapy--the 10-year experience of the French Society of Pediatric Oncology.

PURPOSE: To assess the results and morbidity of treatment of children with localized pelvic neuroblastoma (NB). PATIENTS AND METHODS: All consecutive cases of localized pelvic NB registered in the French multicenter prospective studies NBL90 and NBL94 between 1990 and 1999 were reviewed. Resectability was decided on the basis of clinical and radiologic evaluation. In unresectable tumors, primary chemotherapy (combinations of carboplatin-etoposide and vincristine-cyclophosphamide-doxorubicine) was administered before surgery. RESULTS: Forty-seven children (with 26 resectable tumors and 21 unresectable) were included in this study. At the end of treatment, 31 children were in complete remission (66%). Long-term neurologic sequelae were observed in seven patients (15%), directly attributable to surgery in three cases. After a median follow-up of 48 months (range, 13 to 129 months), 44 patients are alive. Six children experienced local relapse; four of these children achieved subsequent remission. The projected overall survival and event-free survival (EFS) rates at 5 years are, respectively, 93% +/- 4% and 84% +/- 5%. Survival of children treated with preoperative chemotherapy are similar to those treated by primary surgery (80% and 88% respectively). The extent of surgical resection seemed to have no influence on the outcome (EFS rates 76% and 89% in case of gross residue and complete resection or microscopic residue, respectively). CONCLUSION: Our data confirm the excellent survival of localized pelvic NBs. Considering the efficacy of preoperative chemotherapy, patients with pelvic NB should be carefully screened for primary surgery. The risk of neurologic impairment during radical excision should be balanced with the good survival of children with minimal residual disease.     

Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia.

PURPOSE: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. PATIENTS AND METHODS: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. RESULTS: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. CONCLUSION: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.     

Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy.

PURPOSE: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. RESULTS: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.     

Cortical motor and somatosensory representation: effect of cerebral lesions

OBJECT: Changes in cortical representation in patients with cerebral lesions may alter the correlation between cortical anatomy and function. This is of potential clinical significance when the extent of cortical resection is based on surface anatomical landmarks. METHODS: Fifty-one patients with supratentorial lesions were studied. Nineteen harbored noncentral lesions (no involvement of pre- or postcentral gyrus), whereas 32 had central lesions. Control studies consisted of stimulation of the hand contralateral to the unaffected hemisphere. Positron emission tomography activation studies were performed using the [15O]H2O tracer. Somatosensory stimulation of the hand or foot was performed using a mechanical vibrator. Motor activation consisted of hand clenching or foot tapping. The t-statistic volumes were generated from images showing the mean change in regional cerebral blood flow, and coregistered with a T1-weighted magnetic resonance image. At the threshold selected, exclusive contralateral primary sensorimotor cortex activation was elicited in 100% of the control studies. A different pattern of cortical activation was associated with central lesions in 35 (78%) of 45 patients, which occurred significantly more often than with noncentral lesions (eight [31%] of 26 patients). The most common difference in the pattern of activation with central lesions was activation of cortical regions outside the central area (including the supplementary sensorimotor area and the secondary somatosensory cortex). No sensorimotor activation was observed in gyri adjacent to the pre- or postcentral gyrus. CONCLUSIONS: Central lesions are more frequently associated with altered patterns in activation than lesions in noncentral locations. Characteristic patterns include activation of secondary sensorimotor areas. The absence of activation in gyri adjacent to the sensorimotor strip has clinical significance for the planning of resections in the central area.