Quantification of information transfer via cellular signal transduction pathways

OBJECTIVE: Symptomatic malignant pleural effusions are common sequelae in patients with certain malignancies. Pleurodesis via bedside thoracostomy is the current treatment option most commonly used. To our knowledge, this is the first prospective randomized trial to examine which agent, bleomycin or talc slurry, is superior in terms of effectiveness, safety, and cost. PATIENTS AND METHODS: Between July 1992 and March 1995, 35 patients presenting to our medical center with symptomatic malignant pleural effusions were prospectively randomized to undergo chemical pleurodesis with either bleomycin or talc slurry via bedside thoracostomy. The conditions of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs. RESULTS: Twenty-nine patients who underwent 33 treatments (14 with bleomycin and 19 with talc) were available for follow-up. Follow-up ranged from 2 weeks to 8 months (mean, 1.7 months). Both groups demonstrated notable improvement in both pain and dyspnea following treatment, but there were no statistically significant differences between groups in the amount of improvement (two-tailed Student's t test). Permanent control of effusions, defined objectively on chest radiograph, was achieved with 11 bleomycin treatments (79%) and 17 talc treatments (90%) (p=0.388). The procedures were well tolerated and no significant adverse effects were observed. Talc is a much less costly agent than bleomycin ($12.36 cost to our medical center per treatment for talc vs $955.83 for bleomycin). CONCLUSION: Given the similar efficacy and significant cost advantage, we conclude that talc is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions.     

Validation of computerized Swedish dog and cat insurance data against veterinary practice records

Spontaneous cellular reorganisation at the lesion site has been investigated following massive spinal cord compression injury in adult rats. By 2 days post operation (p.o.), haemorrhagic necrosis, widespread axonal degeneration, and infiltration by polymorphnuclear granulocytes and OX42-positive macrophages were observed in the lesion site. By 7 days p.o., low affinity nerve growth factor receptor-positive Schwann cells, from activated spinal roots, were identified as they migrated far into the lesion. Between 7 and 14 days p.o., the overlapping processes of Schwann cells within the macrophage-filled lesion formed a glial framework which was associated with extensive longitudinally orientated ingrowth by many neurofilament-positive axons. Relatively few of these axons were calcitonin gene-related peptide (CGRP)-, substance P (SP)-, or serotonin (5HT)-positive; however, many were glycinergic or gamma aminobutyric acid (GABA)ergic. At 21 and 28 days p.o. (the longest survival times studied), a reduced but still substantial amount of orientated Schwann cells and axons could be detected at distances of up to 5 mm within the lesion. Glial fibrillary acidic protein (GFAP) immunoreactivity demonstrated the slow formation of astrocytic scarring which only became apparent at the lesion interface between 21 and 28 days p.o. The current data suggest the possibility of developing future therapeutic strategies designed to maintain or even enhance these spontaneous and orientated regenerative events.     

Albumin movement out of the subretinal space after experimental retinal detachment

PURPOSE: The subretinal fluid of serous retinal detachments contains protein, but little is known about its origin and fate. The authors designed experiments to study the rate and route of albumin movement out of the subretinal space. METHODS: Experimental retinal detachments were made in Dutch rabbits by injecting Hanks' balanced salt solution containing serum levels (approximately 30 mg/ml) of fluorescein isothiocyanate (FITC) albumin into the subretinal space through a micropipette. Subretinal, vitreous, and serum fluid samples were withdrawn 0 to 4 hours later through a similar micropipette and were analyzed for osmolality, FITC albumin content (by fluorophotometry) and FITC+native albumin content (by gel electrophoresis). Sodium iodate was injected intravenously in some rabbits to damage the retinal pigment epithelium (RPE). RESULTS: Albumin injected into the subretinal fluid diffused steadily into the vitreous, and its concentration decreased by approximately 5% per hour. This rate was unaffected by RPE damage. Albumin did not move into the bloodstream unless the RPE was damaged with sodium iodate, and then it crossed the RPE at approximately 25% of the rate at which it moved into the vitreous. Subretinal fluid osmolality remained within the range of 293 to 294 mOsm/kg despite protein movement and the continual absorption of fluid from the detachments. CONCLUSIONS: These results show that albumin in the subretinal space diffuses readily into the vitreous, and subretinal osmolality changes are rapidly equilibrated with the vitreous. Albumin does not cross normal RPE, and it crosses iodate-damaged RPE more slowly than it crosses retina. Thus, there must be a constant supply of albumin if high subretinal concentrations are to be sustained in clinical serous detachments.     

Cytotoxicity and NMR spectral assignments of ergolide and bigelovin

A 10-year-old left-handed girl with a developmental stutter and agenesis of the corpus callosum with associated hydrocephalus ceased stuttering immediately upon initiation of steroid therapy for colitis. Steroid taper resulted in a recurrence of the stutter and resumption for treatment of recrudescent colitis caused its disappearance again. Baseline agenesis of the corpus callosum with hydrocephalus and the patient's course in the face of the known effects of steroids on white matter lend support to the hypothesis that stuttering reflects anomalous dominance and/or atypical interhemispheric connectivity, as evidenced by the fact that presumed alterations of white matter tracts affected speech rhythms/stuttering.