Visual hallucinations on eye closure associated with atropine toxicity. A neurological analysis and comparison with other visual hallucinations

Visual hallucinations of remarkable intensity began shortly after intravenous atropine and persisted for 11 days. They were present only when the eyes were closed and were associated with heightened dreaming and disturbed sleep. The patient remained lucid and described his experiences to his attendants. Our patient's hallucinations bore some resemblance to hypnagogic hallucinations and this became the basis for the hypothesis that the hallucinations originated in the sleep-dream system of the brain stem. It is speculated that a similar site--a metabolic locus minoris resistentiae may play a part in other types of visual hallucinations and in delirium.     

Physiologically based pharmacokinetic modeling of the pregnant rat: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid

A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the pregnant rat exposed to TCE by inhalation, by bolus gavage, or by oral ingestion in drinking water. The kinetics of trichloroacetic acid (TCA), an oxidative metabolite of TCE, were described by a classical one-compartment pharmacokinetic model. Among the required model parameters for TCE, partition coefficients (PCs) and kinetic constants for oxidation were determined by vial equilibration and gas uptake methods, respectively. The fat:blood PC was 33.9; the blood:air PC was 13.2; and the fetal tissue:fetal blood PC was 0.51. TCE was readily metabolized with high substrate affinity. In naive and pregnant female rats the maximum velocities of oxidative metabolism were 10.98 +/- 0.155 and 9.18 +/- 0.078 mg/kg/hr, while the estimated Michaelis constant for the two groups of rats was very low, 0.25 mg/liter. The first-order rate constant for oral absorption of TCE from water was 5.4 +/- 0.42/hr-1 in naive rats. With TCA, the volume of distribution (0.618 liter/kg) and the plasma elimination rate constant (0.045 +/- 0.0024/hour) were estimated both from intravenous dosing studies with TCA and from an inhalation study with TCE. By comparison of the two routes of administration, the stoichiometric yield of TCA from TCE was estimated to be 0.12 in pregnant rats. To develop a data base for testing the fidelity of the PB-PK model, inhalation and bolus gavage exposures were conducted from Day 3 to Day 21 of pregnancy and a drinking water exposure from Day 3 to Day 22 of pregnancy. Inhalation exposures with TCE vapor were 4 hr/day at 618 ppm. The TCE concentration in drinking water was 350 micrograms/ml and the gavaged rats received single daily doses of 2.3 mg TCE/kg. Time varying physiological parameters for compartment volumes and blood flows during pregnancy were obtained from the published literature. Using the kinetic parameters determined by experimentation, TCE concentrations in maternal and fetal blood and TCA concentrations in maternal and fetal plasma were predicted from the PB-PK model by computer simulation and compared favorably with limited data obtained at restricted time points during pregnancy for all three routes of exposure. On the basis of the PB-PK model, fetal exposure to TCE, as area-under-the-curve, ranged from 67 to 76% of maternal exposure. For TCA the fetal exposure was 63 to 64% of the maternal exposure. The fetus is clearly at risk both to parent TCE and its TCA metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)     

Left atrial myxoma: diagnosis by digital subtraction intravenous angiography

Digital subtraction intravenous angiography (DSIVA) represents an important technical advance in angiographic diagnosis. Herein we present three patients with left atrial myxoma assessed by DSIVA. We review the role of DSIVA in evaluation of patients with suspected cardiac tumors and the importance of careful atrial-phase scrutiny in examinations obtained for other purposes (ie, pulmonary angiography and assessment of ventricular function).     

Differential effects of CO2 and hypoxia on bronchomotor tone in the newborn dog

We compared the effects of hypoxia and hypercapnia on pulmonary mechanics in the newborn dog. Animals were anesthetized with a mixture of chloralose/urethane, paralyzed and ventilated with the chest open. Following an inflation to control volume history, mean inspiratory resistance (RLi) and dynamic compliance (CLdyn) were measured on a breath-by-breath basis during ventilation with control (FIO2 = 0.4), hypoxic (FIO2 = 0.1) and hypercapnic (FICO2 = 0.05) gas mixtures. Hypercapnia increased RLi 63% (n = 9) while hypoxia increased RLi in only 1/9 animals. Neither gas mixture changed CLdyn compared to control. The response to hypercapnia and the lone hypoxic response were eliminated by denervation of the airways by atropine administration or vagotomy. Following airway denervation hypoxia caused a small but statistically significant fall in CLdyn compared to the denervated control. These findings demonstrate that the newborn dog is capable of reflexly increasing bronchomotor tone and that vagal efferent innervation to the airways is functional at birth. Our data also suggest that in the newborn, central chemoreceptors are more effective than peripheral chemoreceptors in altering vagal tone to airway smooth muscle. Increased bronchomotor tone with hypercapnia may help to prevent dynamic compression of the airways.     

Aberrant expression of tight junction-related proteins ZO-1, claudin-1 and occludin in synovial sarcoma: an immunohistochemical study with ultrastructural correlation.

Synovial sarcoma demonstrates epithelial differentiation, either by light microscopy (biphasic synovial sarcoma) or by immunohistochemical/ultrastructural methods only (monophasic) and poorly differentiated synovial sarcoma. Although the glands of synovial sarcoma are known to have tight junction-like structures, far less is known about junction formation in the spindled component of synovial sarcomas. Additionally, it is unknown whether the tight junctions of synovial sarcoma are normally constituted. The tight junction is a multiprotein complex consisting of numerous proteins that include ZO-1, claudin-1 and occludin. A total of 35 cases of synovial sarcoma (13 biphasic, 14 monophasic and eight poorly differentiated) were immunostained for ZO-1, claudin-1 and occludin using commercially available antibodies, heat-induced epitope retrieval and standard avidin-biotin technique. When available, corresponding electron micrographs were reviewed. For five cases, the presence of either an SYT-SSX1 (three cases) or SYT-SSX2 (two cases) gene fusion was known. Positive cases showed particulate membrane staining. The glands of biphasic synovial sarcomas expressed ZO-1 (13/13), claudin-1 (12/13) and occludin (11/13) in a manner identical to normal glandular epithelia, at the apical portion of the lateral membrane. The spindle cells of biphasic synovial sarcomas showed abnormal circumferential membranous expression of ZO-1 (12/13), claudin-1 (6/13) and occludin (3/13). Monophasic synovial sarcomas expressed ZO-1 in a circumferential pattern (13/14) but less often claudin-1 (4/14) or occludin (3/14). Poorly differentiated synovial sarcomas expressed ZO-1 (8/8) and claudin-1 (6/8) but only rarely occludin (2/8). By electron microscopy, recognizable tight junctions were seen only in glands. No correlation was seen between histologic subtype or fusion type and expression of tight junction proteins. We conclude that the glands of biphasic synovial sarcomas show well-organized, true epithelial tight junctions. In contrast, the spindled cells of all synovial sarcomas show significant abnormalities in the expression and localization of tight junction proteins, suggesting partial and/or aberrant epithelial differentiation.     

Free flap reconstruction of the lower extremity in the elderly

Summary Over a four year period, thirteen patients over the age of 60 (mean 69 years) underwent reconstruction of lower extremity defects with free tissue transfers. Ten latissimus dorsi, one tensor facia lata, and two rectus abdominus free flaps were used. Despite significant risk factors which included previous tobacco use, hypertension, diabetes mellitus, and angiographic vessel abnormalities, ten of thirteen cases had successful outcomes. There was one acute flap failure secondary to arterial thrombosis. Four flaps had delayed healing, with one patient eventually requiring amputation secondary to persistent pain and wound drainage. This experience demonstrates that free flap reconstruction of lower extremity defects in the elderly patient is a reasonable alternative to amputation when other options are limited.From the Section of Plastic and Reconstructive Surgery at the Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA Requests for reprints: J. Fisher, M.D.