The impact of sequential quality assessment exercises on laboratory performance: the multicentre ECAT Angina Pectoris Study. Report from the European Concerted Action on Thrombosis and Disabilities (ECAT)

As an adjunct to a European multicentre prospective study, five quality assessment (QA) exercises, spanning a period of 2.5 years, were undertaken. In these, fifteen laboratories from eight countries each performed ten haemostatic factor assays. The design of the QA exercises allowed the between-duplicate, between-day and between-laboratory coefficients of variation (CVs) to be calculated. The between-duplicate CV decreased by a factor of one quarter, and the between-day CV by a factor of one third, over the five exercises. The activated partial thromboplastin time (APTT) assay consistently showed the lowest CVs, while there was notable improvement in the between-day CVs for von Willebrand factor related antigen (vWF R:Ag) and factor VIII clotting activity (VIII:C). However, the between-laboratory CV, assessing extent of agreement between the different laboratories, did not apparently improve over the five exercises. Thus, while QA exercises may be very useful in improving the performance of haemostatic assays according to criteria which an individual laboratory can assess, improving agreement on haemostatic assay results between laboratories may be more difficult to achieve.     

Sudden cervical pain: spontaneous cervical epidural hematoma

Three cases of cervical epidural hematoma are reported. Acute neck pain usually associated with a mild effort, closely followed by radicular pain and a neurologic deficit below the lesion is the typical presentation of this extremely rare and difficult diagnosis. As prognosis depends on preoperative neurologic state, the authors emphasize the importance of prompt identification of this lesion. The diagnosis is confirmed by computed tomography, and emergency neurosurgical laminectomy is mandatory.     

Neurobiology of obsessive compulsive disorder--a serotonergic basis of Freudian repression

Intrusive thoughts and images, often of a violent, horrific, or blasphemous nature are the hallmark of Obsessive Compulsive Disorder (OCD). OCD patients frequently also often have reductions in normal serotonergic (5-HT) function. This paper proposes a model of 5-HT function involving the routine filtering and suppression of violent or libidinal impulses. This model accounts for OCD as an instance of failed inhibition. The model also appears to resemble Freud's model of ego-id interactions at least in part, suggesting that it may be possible to psychobiologically substantiate a Freudian metaphor.     

Double-blind, placebo-controlled comparison of clonazepam and alprazolam for panic disorder

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.     

Lithium treatment of chronic hair pulling

Ten patients with chronic hair pulling received trials of lithium carbonate of 2 to 14 months' duration. Eight patients demonstrated decreased hair pulling and mild to marked hair regrowth. Three responders experienced increased hair pulling subsequent to discontinuation of lithium treatment. Lithium's effect on hair pulling may be related to its observed benefits in treating aggressivity, impulsivity, and mood instability.     

Experimental isovolemic haemodilution-induced augmentation of carotid blood flow and oxygen transport through graded carotid stenoses.

The effect of haemodilution without volume expansion (isovolemic haemodilution) was assessed with respect to blood flow and oxygen transport across stenotic lesions of progressive severity in the dog carotid artery. As the mean haematocrit (Hct) was reduced from 40 +/- 1% (+/- SEM) to 32 +/- 0% (p less than 0.001), reductions in vascular resistance were significant across the 90% (p less than 0.001) and 95% (p less than 0.0003) relative carotid stenoses. Isovolemic haemodilution reduced fresh blood viscosity significantly by 27 +/- 3% (p less than 0.001) and 42 +/- 4% (p less than 0.001) at the low shear rates of 10 sec-1 and 1 sec-1 which are typical of low-flow states. Following a 20% reduction in Hct 30 to 35% increase (p less 0.001) in carotid blood flow occurred at non-critical degrees of stenosis while a mean 83% increase (p less than 0.001) occurred at the highly critical 95% relative stenosis. Oxygen transport after a 22% decrease in blood haemoglobin was significantly increased by 28% (p less than 0.01) at the 95% relative stenosis level. These data provide a physiologic rationale for the beneficial effects of haemodilution in acute cerebral ischaemia, cerebral vasospasm and cerebral revascularization or carotid endarterectomy.     

Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801.

In order to study the involvement of NMDA-receptor activation in brain development, rat pups were chronically treated with the non-competitive NMDA antagonist MK-801 during the neonatal period. We recorded the cortical EEG at various vigilance states throughout the treatment period. Spectral analysis of the EEG showed reduced power in the delta (delta) frequency range (1.5-4 Hz) during quiet sleep and less power in the theta (theta) range (4-7 Hz) during REM-sleep in MK-801 animals than in controls. No significant differences were found for the total time spent in each of the different vigilance states. We conclude that chronic MK-801 treatment probably causes a developmental retardation in state-related brain activities.     

Transneuronal degeneration of thalamic neurons following deafferentation: quantitative studies using [3H]thymidine autoradiography.

Transneuronal degeneration of thalamic neurons following partial deafferentation was studied using [3H]thymidine autoradiography. Timed-pregnant female Sprague-Dawley rats received systemic injections of [3H]thymidine on embryonic day (E) 13, 14 and/or 15. On the day of birth, pups were anesthetized by hypothermia and subjected to unilateral enucleation, unilateral removal of the inferior colliculus or sham lesion. Animals were sacrificed on postnatal day 10 or 30 and the brains processed for autoradiography. Material from sham-lesioned animals demonstrates that neurons destined for the dorsal lateral geniculate nucleus (LGd) undergo final mitoses on E13, 14 and 15. Neurons in the ventral medial geniculate nucleus (MGv) undergo final mitoses on E13 and 14. Thirty days following neonatal unilateral eye removal, the contralateral LGd displays a loss of approximately 30-35% of [3H]thymidine labeled neurons. Neonatal unilateral removal of the inferior colliculus results in a loss of approximately 30-40% of labeled neurons in MGv. For both LGd and MGv, shorter survival times reveal less severe cell loss. Late generated (E15) LGd neurons show less severe loss following enucleation than do earlier generated neurons. These results document the degree of cell loss in sensory thalamic nuclei following deafferentation and demonstrate that [3H]thymidine autoradiography provides a useful quantitative method for assessing anterograde transneuronal cell loss in targeted populations of neurons in the developing central nervous system.     

An in vivo study of the ontogeny of long-term potentiation (LTP) in the CA1 region and in the dentate gyrus of the rat hippocampal formation.

The influences of stimulus intensity, intratrain frequency, and number of trains were studied for their effects on the development of long-term potentiation (LTP) in the hippocampal formation. LTP was analyzed with full input-output curves for population spike (PS) amplitudes (PS-LTP) calculated from responses elicited in the CA1 region and in the dentate gyrus by monosynaptic activation. A standardized protocol employing a sequence of stimuli was devised to systematically compare LTP in the dentate gyrus to that in the CA1 region in rats of various ages ranging from postnatal day (PN) 6 to adults (PN 60). In adult animals, the degrees of LTP were comparable in the dentate gyrus and CA1 region for the 3 stimulus strengths studied (intensity just subthreshold for PS, intensity giving 1/4 maximal PS, and intensity giving 1/2 maximal PS). LTP developed at different rates in the two regions, reaching adult values about two weeks after birth in CA1 but about 3 weeks after birth in the dentate gyrus. We postulate that differences in the rate of development in CA1 and in the dentate gyrus are related to the later neurogenesis of dentate granule cells and also possibly to a later functional maturation of N-methyl-D-aspartate (NMDA) receptor-channel complexes on these cells.     

Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical characterisation of Toxoplasma antigen, infiltrates and major histocompatibility complex gene products

The experimental infection of immunocompetent and immunodeficient athymic mice with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to study the ensuing encephalitic process by use of histological and immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+ and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post-infection because of a generalized toxoplasmosis with predominant involvement of the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation of class I and II major histocompatibility complex (MHC) gene products. Class I antigen was widely expressed on microglial cells and astrocytes. Class II antigen was only expressed on microglial cells despite a considerable astrogliosis. Our results indicate a differential expression of MHC-determined antigens on brain cells in acute and chronic murine Toxoplasma encephalitis.