Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset.

Long-term dopamine replacement therapy of Parkinson's disease leads to the occurrence of dyskinesias. Altered firing patterns of neurons of the internal globus pallidus, involving a pathological synchronization/desynchronization process, may contribute significantly to the genesis of dyskinesia. Levetiracetam, an antiepileptic drug that counteracts neuronal (hyper)synchronization in animal models of epilepsy, was assessed in the MPTP-lesioned marmoset model of Parkinson's disease, after coadministration with (1) levodopa (L-dopa) or (2) ropinirole/L-dopa combination. Oral administration of levetiracetam (13-60 mg/kg) in combination with either L-dopa (12 mg/kg) alone or L-dopa (8 mg/kg)/ropinirole (1.25 mg/kg) treatments was associated with significantly less dyskinesia, in comparison to L-dopa monotherapy during the first hour after administration. Thus, new nondopaminergic treatment strategies targeting normalization of abnormal firing patterns in basal ganglia structures may prove useful as an adjunct to reduce dyskinesia induced by dopamine replacement therapy without affecting its antiparkinsonian action.     

Dynamic contrast-enhanced MR imaging assessment of vascularized free fibular grafts

Magnetic resonance (MR) imaging may be a noninvasive method for assessing perfusion of vascularized bone grafts placed for treatment of avascular necrosis. One proximal femur of seven beagles was devascularized, with insertion of a vascularized fibular graft. MR imaging at 1 week (seven dogs) and 6 weeks (five dogs) after surgery included pre- and postcontrast spin-echo sequences, unenhanced twodimensional time-of-flight (TOF) vascular imaging, and dynamic gradient-echo imaging during infusion of gadolinium. Relative signal intensity values of selected regions obtained from the dynamic gradientecho images were plotted as percent enhancement versus time. In the operated hip, MR imaging did not show enhancement in six of seven femoral heads and greater trochanters at 1 week after surgery, with similar results after 6 weeks. MR imaging of fibular grafts 6 weeks after surgery showed an initial rapid increase in enhancement and a subsequent slower increase in five of five dogs, although no enhancement was seen in six of seven dogs at 1 week. These findings contrasted with a rapid initial increase in enhancement followed by slow decline in non-operated hips. Two-dimensional TOP imaging did not show the vascular pedicle of the graft in any dog. Findings of radionuclide bone scanning performed 1 week after surgery were consistent with devascularization of the operated femur and fibular graft. However, tetracycline distribution and histologic findings confirmed the viability of five of five grafts within the devascularized femurs 6 weeks after surgery. Thus, dynamic contrast-enhanced MR imaging at 6 weeks after surgery is valuable for assessing vascular bone graft perfusion, while similar imaging at 1 week may suggest otherwise.     

Subjective perceptions and physiological variables during weaning from mechanical ventilation.

BACKGROUND: As costs related to mechanical ventilation increase, clear indicators of patients' readiness to be weaned are needed. Research has not yet yielded a consensus on physiological variables that are consistent correlates of weaning outcomes. Subjective perceptions rarely have been examined for their contribution to successful weaning. OBJECTIVE: To explore the subjective perceptions of dyspnea, fatigue, and self-efficacy and selected physiological variables in patients being weaned from mechanical ventilation. METHODS: Data were collected prospectively on 68 patients being weaned from mechanical ventilation. Subjective perceptions were measured by using 3 visual analog scales; physiological variables were measured by using the Burns Weaning Assessment Program and a patient profile. Weaning outcomes were recorded 24 hours after data collection. RESULTS: Participants were primarily white women and required mechanical ventilation for a mean of less than 4 days. Participants reported mild dyspnea, moderate fatigue, and high weaning self-efficacy. High PaO2, low PaCO2, stable hemodynamic status, adequate cough and swallow reflexes, no metabolic changes, and no abdominal problems were associated with complete weaning (P = .05). Subjective perceptions were associated with physiological variables but not with weaning outcomes. CONCLUSIONS: Multidimensional assessment of both primary and secondary indicators of readiness to be weaned is necessary for timely, efficient weaning from mechanical ventilation. Primary assessments include physiological variables related to gas exchange, hemodynamic status, diaphragmatic expansion, and airway clearance. Secondary assessments include perceptions related to key physiological variables. Additional research is needed to determine the predictive value of physiological variables and perceptions of dyspnea, fatigue, and self-efficacy.     

Perinatal 'TORCH' infections identified by serology: correlation with abnormalities in the children through 7 years of age.

A matched case-control methodology was used to assess the risk for a wide range of abnormalities in children associated with serological evidence for 'TORCH' infections in the mothers. Specimens were selected from the large bank of sera from the approximately 54,000 pregnant women who participated in the Collaborative Perinatal Project. There was no clear association between any of the antigens studied and any specific damage to the child. These 'negative' findings are consistent with the absence of frequent significant effects due to these agents in the second and third trimesters of pregnancy.     

Chronic fatigue syndrome: traditional and community-based approaches to rehabilitation

Chronic fatigue syndrome (CFS) is a controversial condition defined by 6 months or more of unexplained fatigue, and at least four out of eight cognitive and physical symptoms. Over the past 2 decades, CFS has been the subject of significant debate regarding its definition, cause and recommended treatment. Because a cure for the syndrome has not yet been located, efforts to improve functioning and overall quality of life through rehabilitation represent the most practised form of treatment to date. However, controversy remains as to which approach to rehabilitation is most effective for individuals with CFS. Interventions which take place within real‐world environments and utilise community‐based organizations such as centres for independent living offer a newly explored means of support and rehabilitation. The present paper reviews a variety of approaches to rehabilitation for individuals with CFS, describing their applications with different types of patients, and providing critical commentary on the research methodologies used to evaluate them. Innovative community‐based rehabilitation programmes and their outcomes are described as an alternative with some promise that may compliment more traditional approaches.     

Leukaemia Inhibitory Factor or Related Factors Promote the Differentiation of Neuronal and Astrocytic Precursors within the Developing Murine Spinal Cord

Previously we have shown that leukaemia inhibitory factor (LIF) potentiates the development of murine spinal cord neurons in vitro , suggesting that it, or related factors, may play an important regulatory role in neuronal development. We have further investigated this role and show here that the generation of neurons in cultures of embryonic day 10 spinal cord cells is inhibited by antibodies to the β subunit of the LIF receptor. Since there are more undifferentiated precursors in antibody-treated cultures than in control and LIF-treated cultures, it is concluded that the primary action of LIF, or related molecules, is to promote neuronal differentiation, not precursor survival. In addition, the failure of LIF to support neuronal survival in the period immediately following differentiation suggests that the increased numbers of neurons generated with LIF are not attributable to its neurotrophic action. By selecting neuronal precursors on the basis of their inability to express class I major histocompatibility complex molecules, it was shown that LIF acted directly upon these cells and not via an intermediary cell. LIF also appears to be involved in regulating the differentiation of astrocytes, since it increases the number of glial fibrillary protein (GFAP)-positive cells present in the cultures and since the spontaneous production of GFAP-positive cells is blocked by antibodies to the LIF β receptor. These findings suggest that LIF or related factors promote the differentiation of neural precursors in the spinal cord, but that they are not involved in preferentially promoting precursors down a specific differentiation pathway.     

Partial resolution of acute interstitial pneumonia in native lung after single lung transplantation.

The case of a 49 year old man presenting with rapidly progressive interstitial lung disease is described. Radiological findings and the lung biopsy specimen were compatible with an acute interstitial pneumonia, as was the relentless clinical course culminating in hypoxic respiratory failure. After right single lung transplantation there was considerable improvement in lung function and radiographic clearing of disease in the native left lung.