Should we abandon the APTT for monitoring unfractionated heparin?

INTRODUCTION: The activated partial thromboplastin time (APTT) is commonly used to monitor unfractionated heparin (UFH) but may not accurately measure the amount of heparin present. The anti-Xa assay is less susceptible to confounding factors and may be a better assay for this purpose. MATERIALS AND METHODS: The validity of the APTT for monitoring UFH was assessed by comparing with an anti-Xa assay on 3543 samples from 475 patients (infants [n=165], children 1-15years [n=60] and adults [n=250]) receiving treatment dose UFH. RESULTS: Overall concordance was poor. The highest concordance (66%; 168/254) was seen in children. Concordance (51.8%) or discordance (48.4%) was almost equal in adult patients. Among adult patients whose anti-Xa level was within 0.3-0.7IU/mL, only 38% had an APTT in the therapeutic range whilst 56% were below and 6% were above therapeutic range. Children and adult patients with anti-Xa of 0.3-0.7IU/mL but sub- therapeutic APTT had significantly higher fibrinogen levels compared to those with therapeutic or supra-therapeutic APTT. CONCLUSIONS: When the anti-Xa level was 0.3-0.7IU/mL, the majority of samples from infants demonstrated a supra-therapeutic APTT, whilst adults tended to have a sub-therapeutic APTT. This may lead to under anticoagulation in infants or over anticoagulation in adults with risk of bleeding if APTT is used to monitor UFH. These results further strengthen existing evidence of the limitation of APTT in monitoring UFH. Discordance of APTT and anti-Xa level in adults and children may be due to elevation of fibrinogen level.

Electrical activity regulates dendritic reorganization in ganglion cells after neonatal retinal lesion in the cat.

During the first month of postnatal life, the dendritic arborizations of cat retinal ganglion cells continue to develop and undergo a substantial remodeling. Mechanical and pharmacological interferences with the normal development induce, during this period of time, substantial modifications in ganglion cell morphology. Specifically, the degeneration of those neurons whose axons were severed by a neonatal retinal lesion leads to a zone depleted of ganglion cells. Neurons at the border of the depleted area develop an abnormal elongation of the dendritic trees toward the empty space. In the present paper, we report data showing that this dendritic reorganization can be prevented by blocking the electrical activity with repeated tetrodotoxin injections into the eye during the whole critical period. Our analysis was performed on neurons filled with horseradish peroxidase.

Evidence that the influence of ganglion cell axons on astrocyte morphology is mediated by action spike activity during development.

In many mammal retinas, the morphology of astrocytes is strongly influenced by nearby axons of ganglion cells. Astrocyte processes stretch along the axons, fine extensions of the processes contact node-like specialisation of the axon membrane and the morphology of the adult astrocyte is strongly determined by this relationship. The mechanism which attracts astrocyte processes to contact specific regions of the axon membrane is not known however. This study presents evidence that in the neonatal cat blocking the impulse activity of ganglion cells with the Na+-channel blocker tetrodotoxin (TTX) leads to a loss of the axon-related morphology of astrocytes. The morphological change induced in astrocytes by TTX was greater in younger animals and could not be detected in the adult. Conversely, if the TTX block was maintained for 4 postnatal weeks the changes induced in astrocytes persisted at least to 13 weeks. The TTX-induced loss of axon-related morphology in astrocytes suggests that the signal by which axons attract astrocyte processes to contact the axonal membrane in ways which modify astrocyte morphology is released by action spike activity during development.

Interplay between the dendritic trees of alpha and beta ganglion cells during the development of the cat retina.

We have analyzed the effect of a small lesion to the retina of a two-day-old kitten and observed that after degeneration of ganglion cells whose axons were severed, a restricted region of the retina remained depleted of cells. Cells located near the borders of the depleted zone showed an abnormal elongation of dendrites towards the bare area. By means of a computer-aided system, we analyzed the whole population of cells at the two borders, and in agreement with previous data found that the effect was most prominent at the border and progressively decreased to eventually disappear at a distance of approximately 500 microns. The distance from the border, however, is not the only factor to influence the degree of asymmetry; with comparable distances, the vicinity of an alpha-cell reduces the projection of the beta-cell dendrites toward the empty area. We suggest that the organization of the adult retinal pattern is also influenced by interactions occurring between dendrites of different classes of ganglion cells.

Binding pattern of alpha-bungarotoxin on horizontal cells of a marine teleost retina.

A conjugate of alpha-bungarotoxin and a fluorescent marker (fluorescein isothiocyanate) has been used to localize "nicotinic" acetylcholine receptors on neurons in the outer plexiform layer of marine teleost retina. Toxin binding was confined to bipolar cell dendrites and to intermediate horizontal cells. The arrangement of labeled horizontal cells appears irregular in the whole retina, with a peak density in the ventral and dorsal quandrants. Alpha-bungarotoxin receptors on horizontal cells differ from those on bipolar cells and from those on dendrites in the inner plexiform layer in their sensitivity to agonists and antagonists such as d-tubocurarine and nicotine. They constitute a different type of "nicotinic" receptor that probably has a different function.

Differentiation, extent and layering of amacrine cell dendrites in the retina of a sparid fish.

The morphology of amacrine cells has been studied in Golgi-stained retinae of the salt water sparid Boops boops. The great variety of size and shapes of amacrine cells has been organized into five classes according to the qualitative parameter 'dendritic architecture', which describes the number, size, course, degree of dichotomy, and varicosity of dendrites. Extent of dendritic field and depth of stratification in the inner plexiform layer, viewed as quantitative variations of a given cell type morphology, complete the criteria for classification. Each amacrine cell is unequivocally defined by a three element code according to the values assumed by the parameters used for the classification. The possible functional implications of dendritic morphology are briefly discussed.

beta-Glucuronidase activity in the developing uropygial gland.

The presence of sterolic compounds and beta-glucuronidase activity have been studied in the uropygial glands of chick embryos (18th day of inc.), chickens (3 weeks after hatching) and young fowls (5 months old). Sterols are histochemically detectable only after hatching and beta-glucuronidase activity, very faint before hatching, reaches its maximum in chicken glands with a peculiar inner localization coincident with sterolic localization. It is suggested that beta-glucuronidase has in uropygial gland a double functional significance: a certain amount of activity is developed to cell proliferation whereas a more strong activity is involved in the hydrolysis of sterol glucuronides.

Occurrence of 7-dehydrocholesterol in the uropygial gland of domestic fowls.

Histochemical studies on the uropygial gland of domestic fowls have shown the presence of sterols (among which cholesterol and its esters) in the lipidic fraction of the gland secret. beta-Glucuronidase activity beside A5 3beta- and 17beta-hydroxysteroid dehydrogenase activities suggests that uropygial gland might be involved in sterols metabolism. By thin layer chromatography cholesterol and 7-dehydrocholesterol can be separated from the uropygial extracts and these compounds can be identified in gas liquid chromatography.