Cytologic diagnosis of peritoneal fluids. Applicability to the laparoscopic diagnosis of endometriosis

OBJECTIVE: To determine the accuracy of cytologic examination of laparoscopically obtained peritoneal fluid in the diagnosis of endometriosis. STUDY DESIGN: This investigation analyzed 50 laparoscopic fluid specimens received over a three-year period. Retrospective cytologic findings were correlated with clinical history and laparoscopic diagnoses. Touch preparations were also collected from necropsies to develop cytologic criteria necessary to distinguish endometrial cells from mesothelial cells. RESULTS: The presence of hemosiderin-laden macrophages in peritoneal fluids was more specific but less sensitive than the presence of endometrial cells for the diagnosis of endometriosis. CONCLUSIONS: In women undergoing laparoscopy to detect endometriosis, the identification of endometrial cells alone in peritoneal fluids may not be sufficient to render a definitive diagnosis of endometriosis. However, the presence of hemosiderin-laden macrophages in this population should alert the cytologist to that possibility.     

Metabolism of nicotine by human liver microsomes: stereoselective formation of trans-nicotine N'-oxide

Liver microsomes from humans catalyze the NADPH-dependent oxidation of (S)-nicotine. The principal product is the 5'-carbon atom oxidation product, nicotine delta 1',5'-iminium ion, which is efficiently converted to the gamma-lactam derivative cotinine in the presence of aldehyde oxidase. Another major product is nicotine N'-oxide. In contrast to previous reports describing in vitro or in vivo studies, formation of only trans-nicotine N'-oxide was observed. Demethylation of nicotine was not observed. Studies on the biochemical mechanism of nicotine 5-carbon atom oxidation strongly implicate one major cytochrome P-450 isoenzyme (i.e., P-450 2A6) as largely responsible for delta 1',5'-iminium ion formation. Stereoselective formation of trans-nicotine N'-oxide may be catalyzed in large part by the flavin-containing monooxygenase (form II). These conclusions are based on the effects of alternate substrates for the flavin-containing monooxygenase, heat inactivation studies, immunoblot studies, and selective substrates for cytochromes P-450. The results suggest that (S)-nicotine trans N'-oxygenation and delta 1',5'-iminium ion formation may be selective probes of human liver flavin-containing monooxygenase form II and cytochrome P-450 2A6 activities, respectively, useful for in vivo phenotyping of humans.     

Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain

How neuronal activity changes cerebral blood flow is of biological and practical importance. The rodent whisker-barrel system has special merits as a model for studies of changes in local cerebral blood flow (LCBF). Stimulus-evoked changes in neural firing and 'intrinsic signals' recorded through a cranial window were used to define regions of interest for repeated flow measurements. Whisker-activated changes in flow were measured with intravascular markers at the pia. LCBF changes were always prompt and localized over the appropriate barrel. Stimulus-related changes in parenchymal flow monitored continuously with H2 electrodes recorded short latency flow changes initiated in middle cortical layers. Activation that increased flow to particular barrels often led to reduced flow to adjacent cortex. Dye was injected into single penetrating arterioles from the pia of the fixed brain and injected into arterioles in slices of cortex where barrels were evident without stains. Arteriolar and venular domains at the surface were not directly related to underlying barrels. Capillary tufts in layer IV were mainly coincident with barrels. The matching between a capillary plexus (a vascular module) and a barrel (a functional neuronal unit) is a spatial organization of neurons and blood vessels that optimizes local interactions between the two. The paths of communication probably include: neurons to neurons, neurons to glia, neurons to vessels, glia to vessels, vessels to vessels and vessels to brain. Matching a functional grouping of neurons with a vascular module is an elegant means of reducing the risk of embarrassment for energy-expensive neuronal activity (ion pumping) while minimizing energy spent for delivery of the energy (cardiac output). For imaging studies this organization sets biological limits to spatial, temporal and magnitude resolution. Reduced flow to nearby inactive cortex enhances local differences.     

Foot dystonia and lumbar canal stenosis

We describe a patient who developed involuntary, painless, dystonic contraction of the toes of the right foot on standing or walking. The development of this abnormal movement had been preceded by sensory disturbance on the soles of both feet, triggered by dorsiflexion of the feet. Examination showed that weight bearing on the right foot and walking brought on clawing of the toes of the right foot, which was relieved within seconds of taking pressure off the right foot. There was sensory and reflex evidence of bilateral S1 root disturbance confirmed by electrophysiology. Magnetic resonance imaging of the lumbar spine showed marked stenosis of the lumbar canal with compression of the L5 and S1 nerve roots bilaterally. The patient underwent a lumbar laminectomy with nerve root exit foramina decompression, which abolished the foot dystonia and has considerably improved the sensory disturbance. This case demonstrates that lumbar canal stenosis and/or nerve root compression, may be responsible for foot dystonia. Amelioration of the abnormal movement by surgical decompression argues strongly in favour of this hypothesis.     

G protein-coupled receptor kinase specificity for phosphorylation and desensitization of alpha2-adrenergic receptor subtypes

The alpha2-adrenergic receptor (alpha2AR) subtype alpha2C10 undergoes rapid agonist-promoted desensitization which is due to phosphorylation of the receptor. One kinase that has been shown to phosphorylate alpha2C10 in an agonist-dependent manner is the betaAR kinase (betaARK), a member of the family of G protein-coupled receptor kinases (GRKs). In contrast, the alpha2C4 subtype has not been observed to undergo agonist-promoted desensitization or phosphorylation by betaARK. However, the substrate specificities of the GRKs for phosphorylating alpha2AR subtypes are not known. We considered that differential capacities of various GRKs to phosphorylate alpha2C10 and alpha2C4 might be a key factor in dictating in a given cell the presence or extent of agonist-promoted desensitization of these receptors. COS-7 cells were co-transfected with alpha2C10 or alpha2C4 without or with the following GRKs: betaARK, betaARK2, GRK5, or GRK6. Intact cell phosphorylation studies were carried out by labeling cells with 32Pi, exposing some to agonist, and purifying the alpha2AR by immunoprecipitation and SDS-polyacrylamide gel electrophoresis. BetaARK and betaARK2 were both found to phosphorylate alpha2C10 to equal extents (>2-fold over that of the endogenous kinases). On the other hand, GRK5 and GRK6 did not phosphorylate alpha2C10. In contrast to the findings with alpha2C10, alpha2C4 was not phosphorylated by any of these kinases. Functional studies carried out in transfected HEK293 cells expressing alpha2C10 or alpha2C4 and selected GRKs were consistent with these phosphorylation results. With the marked expression of these receptors, no agonist-promoted desensitization was observed in the absence of GRK co-expression. However, desensitization was imparted to alpha2C10 by co-expression of betaARK but not GRK6, while alpha2C4 failed to desensitize with co-expression of betaARK. These results indicate that short term agonist-promoted desensitization of alpha2ARs by phosphorylation is dependent on both the receptor subtype and the expressed GRK isoform.     

The clinico-neuropsychological manifestations of arteriovenous malformations of the thalamus

A comprehensive clinical and neuropsychological study was made of 34 patients with thalamic arteriovenous malformations. In the thalamus. Memory disorders were a common abnormality (in 31 of 34 patients). They were modally nonspecific and depended on the site of arteriovenous malformations. With the prevalent ventricular pattern of hemorrhages, memory disorders were accompanied by disorientation and emotional and volitional impairments. Arteriovenous malformation was removed in 12 patients (on the left side in 7 patients and on the right in 5). After surgery there was virtually progression of memory defects in all patients. Speech disorders combining the specific features of lesions in various cortical regions were detected in 5 of 7 patients with left thalamic arteriovenous malformations.