The effects of erythromycin on the viability and the secretion of TNF-alpha and TGF-beta1 and expression of connexin43 by human pleural mesothelial cells

OBJECTIVE: The mechanism by which erythromycin produces pleurodesis remains unknown. The purpose of this study was to investigate the effects of erythromycin on human pleural mesothelial cell (HPMC) viability, the secretion of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(1) (TGF-beta(1)) and the level of expression of connexin43. METHODOLOGY: HPMC were incubated with different concentrations of erythromycin. The inhibitory effects of erythromycin on HPMC growth were measured using a tetrazolium-based colorimetric assay. The levels of TNF-alpha and TGF-beta(1) in supernatants were measured by ELISA and levels of connexin43 were assessed by Western blot. RESULTS: Erythromycin injured HPMC in a dose and time-dependent manner. The secretion of both TNF-alpha and TGF-beta(1) by HMPC increased significantly when they were incubated with 100 mg/L erythromycin for 3 or 5 days. The levels of connexin43 in HPMC decreased after incubation with 100 mg/L erythromycin and no relationship was observed between the levels and incubation time. CONCLUSIONS: Erythromycin injures HPMC in a dose- and time-dependent manner and results in the secretion of TNF-alpha and TGF-beta(1). This is one possible mechanism of pleurodesis with erythromycin. Furthermore, erythromycin decreased the levels of connexin43 in HPMC, which could possibly affect the response of HPMC to pleurodesis with erythromycin.     

Stability of mismatch negativity deficits and their relationship to functional impairments in chronic schizophrenia

OBJECTIVE: Because previous studies have demonstrated that patients with chronic schizophrenia have deficits in mismatch negativity associated with poor everyday functioning, the authors investigated the longitudinal stability of mismatch negativity deficits and their longitudinal relationship to poor functional status. METHOD: Ten patients with chronic schizophrenia underwent testing twice over a 1-2-year period. Tests used included mismatch negativity, the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, and the Global Assessment of Functioning Scale. Patients' test results from both sessions were compared with results for 10 age-matched normal subjects. RESULTS: Patients with schizophrenia had mismatch negativity deficits with large effect sizes that were reliable over time. Mismatch negativity deficits were also significantly associated with poor functional status at both the first and second session. CONCLUSIONS: Mismatch negativity deficits and their relationship to poor functional status are stable over time in patients with chronic schizophrenia, suggesting that mismatch negativity may be useful for assessing medication response and other factors in longitudinal studies. Future studies will clarify the emergence, progression, and treatment effects of mismatch negativity deficits in patients with schizophrenia.     

P50 suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment.

BACKGROUND: Identification of individuals at risk for the development of schizophrenia is important because it can lead to a greater understanding of the early stages of the illness. The aim of the present study was to determine whether individuals "at risk" for schizophrenia have deficits in P50 suppression, a preattentive measure of sensory gating. METHODS: Thirty-one at-risk and 21 normal comparison subjects were referred to the CARE (Cognitive Assessment and Risk Evaluation) Program at University of California San Diego. The primary aim of the CARE Program is to identify individuals who are at the greatest risk for conversion to psychosis, with a combination of clinical, familial, and vulnerability markers, including P50 suppression. RESULTS: As a group, the at-risk subjects had modestly lower levels (effect size=.43) of P50 suppression (55.1%, SD=39.8) relative to comparison subjects (71.5%, SD=34.7). At-risk subjects with a first-degree relative with schizophrenia had profoundly deficient P50 suppression (16.4%, SD=33.8) compared with other at-risk (p<.05) and comparison subjects (p<.005). CONCLUSIONS: Ongoing longitudinal follow-up studies will determine whether it is possible to improve the predictive validity of the clinical and familial variables by using P50 suppression alone or in combination with other measures in determining which individuals are at greatest risk for schizophrenia.     

Dead space and paediatric anaesthetic equipment: a physical lung model study

Untested assumptions have been made with regard to functional dead space in facemasks, filters and breathing systems used in children for the administration of inhalation anaesthesia. Total functional dead space was measured in various combinations of this equipment applied to a spontaneous ventilation lung model with parameter settings appropriate for infants of 7-8 kg. We found that functional dead space was too large to allow for spontaneous ventilation of the lungs when a breathing filter was fitted. There was minimal relationship between size of the facemask and functional dead space; however, the provision of 22-mm female inlets to facemasks achieved proportionately less functional dead space than with 15-mm male inlets. Regardless of the apparatus used and the magnitude of the dead space, the leak induced when a poorly fitting facemask was used dramatically reduced the dead space of the breathing system - to near optimal conditions - by moving the alveolar gas elimination point to within the facemask itself.     

Transtympanic perfusion: indications and limitations

PURPOSE OF REVIEW: To review the most recent literature regarding the application of transtympanic inner ear perfusion in the treatment of inner ear disorders including Meniere disease, sudden sensorineural hearing loss, and autoimmune inner ear disease. RECENT FINDINGS: The use of gentamicin perfusion in the management of Meniere disease with intractable vertigo has been demonstrated to have a very high rate of success, and is much less invasive than alternative surgical procedures such as vestibular nerve section or labyrinthectomy. The technique for achieving the highest rate of success while still minimizing the risk of cochleotoxicity continues to be investigated. Sustained delivery techniques such as the Silverstein MicroWick appear to achieve the best pharmacokinetic profile within the inner ear fluids. The end point of treatment does not necessarily require complete vestibular ablation to cure the patient, and shorter courses of treatment may help to reduce the risk of hearing loss. Cochlear Meniere disease can be treated with dexamethasone 4 mg/cc perfusion of the inner ear, which may improve the hearing, tinnitus, and pressure in the ear. Sudden sensorineural hearing loss has been managed with transtympanic steroid delivery, and this appears to be beneficial for some patients who have failed to respond to oral steroids, or have medical contraindications to systemic steroids. SUMMARY: Inner ear perfusion via transtympanic delivery is an emerging technique in the management of inner ear disease. Improved results are expected over time as research in this area answers questions about dosage and delivery techniques, as well as identifying new applications and pharmaceuticals.     

Marker placement to describe the wrist movements during activities of daily living in cyclical tasks

OBJECTIVE: To describe the wrist kinematics during movement through free range of motion and activities of daily living using a cyclical task. DESIGN: The wrist angles were initially calculated in a calibration trial and then in two selected activities of daily living (jar opening and carton pouring). BACKGROUND: Existing studies which describe the wrist movement do not address the specific application of daily activities. Moreover, the data presented from subject to subject may differ simply because of the non-cyclical nature of the upper limbs movements. METHODS: The coordinates of external markers attached to bone references on the forearm and dorsal side of the hand were obtained using an optical motion capture system. The wrist angles were derived from free motion trials and successively calculated in four healthy subjects for two specific cyclical daily activities (opening a jar and pouring from a carton). RESULTS: The free motions trial highlighted the interaction between the wrist angles. Both the jar opening and the carton pouring activity showed a repetitive pattern for the three angles within the cycle length. In the jar-opening task, the standard deviation for the whole population was 10.8 degrees for flexion-extension, 5.3 degrees for radial-ulnar deviation and 10.4 degrees for pronation-supination. In the carton-pouring task, the standard deviation for the whole population was 16.0 degrees for flexion-extension, 3.4 degrees for radial-ulnar deviation and 10.7 degrees for pronation-supination. CONCLUSION: Wrist kinematics in healthy subjects can be successfully described by the rotations about the axes of marker-defined coordinates systems during free range of motion and daily activities using cyclical tasks. RELEVANCE: This study explores the kinematics of the wrist during free motion and daily activities. The technique can be used by the clinician to describe the upper limbs joint angles from a functional perspective.     

Preattentional and attentional cognitive deficits as targets for treating schizophrenia

Background and rationale Pharmacotherapy of schizophrenia has traditionally targeted positive psychotic symptoms. An emerging view is that developing medications that improve cognition in schizophrenia patients is a major step forward in achieving better functional outcome. The cognitive deficits that are often observed in schizophrenia can be assessed using (1) neuropsychological tests; and (2) neurophysiological tests, the topic of this article. These neurophysiological measures cover a spectrum from automatic preattentional to attention-dependent processes.Objectives This article focuses on cognitive deficits that appear to be promising targets for a new third generation of medications that may be used to treat schizophrenia and other patients with specific deficits in cognition and functioning. We discuss the possible use of the following six measures of preattentional and attention-dependent cognitive deficits: mismatch negativity, P50 event-related potential suppression, prepulse inhibition of the startle response, P300 event-related potential, continuous performance task performance, and oculomotor antisaccade performance.Conclusions The use of preattentional and attention-dependent measures offer unique opportunities to improve our armamentarium of pharmacologic strategies for the treatment of cognitive deficits in schizophrenia patients. This review illustrates the usefulness of these measures as targets for existing and new antipsychotic medications that will potentially (1) characterize the cognitive deficits that occur in schizophrenia patients and (2) assess medication-related improvement on these measures and the potential associated improvement in functional outcome.