Airway and body surface sensors for triggering in neonatal ventilation

Failure of neonatal patient triggered ventilation may reflect a delay in delivery of flow relative to the inspiratory effort of the infant. Transmission of diaphragmatic contraction to the sensor site (patient delay) and further transmission to and within the sensing device (device delay) both contribute to the delay in triggering. Patient and device delays were studied for different sensing systems in 36 infants, 24 of whom were intubated. Device delay was long (<40 ms) with a conventional apnoea monitor compared with sensors placed at the airway opening (2 ms), the inspiratory (12 ms) and expiratory (3 ms) pressure transducers of the ventilator, the Graseby capsule (8 ms), strain gauges (3 ms) and oesophageal pressure (6 ms). In near normal infants, the sum of patient and device delays for the latter sensors was less than 20 ms and a minor component of the total delay. However, in severe lung disease the total delay may be more than 100ms even for airway sensors.     

Evidence for involvement of nitric oxide and GABA(B) receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex

Systemic administration of NMDA receptor antagonists elevates extracellular glutamate within prefrontal cortex. The cognitive and behavioral effects of NMDA receptor blockade have direct relevance to symptoms of schizophrenia, and recent studies demonstrate an important role for nitric oxide and GABA(B) receptors in mediating the effects of NMDA receptor blockade on these behaviors. We sought to extend those observations by directly measuring the effects of nitric oxide and GABA(B) receptor mechanisms on MK-801-induced glutamate release in the prefrontal cortex. Systemic MK-801 injection (0.3 mg/kg) to male Sprague-Dawley rats significantly increased extracellular glutamate levels in prefrontal cortex, as determined by microdialysis. This effect was blocked by pre-treatment with the nitric oxide synthase inhibitor l-NAME (60 mg/kg). Reverse dialysis of the nitric oxide donor SNAP (0.5-5 mM) directly into prefrontal cortex mimicked the effect of systemic MK-801, dose-dependently elevating cortical extracellular glutamate. The effect of MK-801 was also blocked by systemic treatment with the GABA(B) receptor agonist baclofen (5 mg/kg). In combination, these data suggest increased nitric oxide formation is necessary for NMDA antagonist-induced elevations of extracellular glutamate in the prefrontal cortex. Additionally, the data suggest GABA(B) receptor activation can modulate the NMDA antagonist-induced increase in cortical glutamate release.     

Validity and reliability of the Geriatric Anxiety Inventory in Parkinson's disease*†

Aim: To examine the psychometric properties of a novel anxiety rating scale, the Geriatric Anxiety Inventory (GAI) in Parkinson's disease (PD). Method: The predictive validity of the GAI was tested against the presence of any DSM‐IV anxiety disorders in 58 PD patients using receiver operating curve analysis. The concurrent validity of this scale was also studied against the state half of the Spielberger State Trait Anxiety Inventory (STAI). The internal consistency and test–retest reliability of the GAI were also examined. Results: The GAI displayed good concurrent validity against the STAI and the DSM‐IV. It also showed good internal consistency and test–retest reliability. Conclusions: This study suggested that the GAI is an appropriate scale to use in non‐demented PD patients.     

Risperidone pretreatment prevents elevated locomotor activity following neonatal hippocampal lesions.

Long-standing behavioral abnormalities emerge after puberty in rats following neonatal hippocampal lesion, providing a developmental model of abnormal rat behavior that may have predictive validity in identifying compounds effective in treating symptoms of schizophrenia. We sought to test the predictive validity of the neonatal hippocampal lesion model in identifying preventive treatment for first-episode psychosis. We determined the effect of risperidone, recently studied for prevention of first-episode psychosis, on the development of elevated locomotor activity following neonatal hippocampal lesions. Rat pups received hippocampal or sham lesions on postnatal day 7, followed by treatment with risperidone or vehicle from postnatal days 35 to 56. Locomotor activity in response to novelty, amphetamine, and nocturnal locomotion were determined on postnatal day 57. Low-dose risperidone (45 microg/kg) pretreatment prevented elevated locomotor activity in some, but not all, of the behavioral tasks following neonatal hippocampal lesions. In contrast, higher risperidone pretreatment was less effective in preventing elevated locomotor activity following neonatal hippocampal lesions. Because low risperidone dosages were also found to be effective in preventing first-episode psychosis in human studies, these data support the predictive validity of the hippocampal lesion model in identifying medications for prevention of first-episode psychosis. Additionally, these data support the use of low-dose risperidone in psychosis prevention, and suggest the possibility that higher risperidone doses could be less effective in this application.     

Bimodal effect of amphetamine on motor behaviors in C57BL/6 mice

Amphetamine-induced motor behaviors, i.e., locomotor and stereotypic activities, were simultaneously characterized in C57BL/6 mice, a strain commonly used for genetic studies. Our findings show relatively high levels of focused activities in drug-naive C57BL/6 mice, confirming the lively nature of this mouse strain. Acute amphetamine induced a dose-dependent, bimodal response: locomotion predominated at lower doses of amphetamine and was gradually displaced by stereotypic behavior as dose and time increased. The sum total of both behavioral activities increased with amphetamine dose, supporting the notion that amphetamine-induced locomotion and stereotypy form a continuum. These data provide a basis for using C57BL/6 mice as a strain to study the molecular and cellular mechanisms underlying psychostimulant effects, drug addiction and psychotic disorders.     

The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation

Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncog-ene results in persistent mitogenic signalling. Upregul-ated c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retino-blastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cyto-toxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.