Aggressive orbital optic nerve meningioma with benign microscopic features: a case report.

Primary optic nerve meningiomas occur at lower ages than meningiomas arising from the coverings of the brain and spinal cord. Here we report the case of a 20-year-old female with an aggressive orbital meningioma referred to the Ophthalmology Department of the Farabi Hospital in Tehran. The patient had a history of orbital meningioma from 10 years ago and several surgical resections due to tumor recurrence during these 10 years. On admission, the patient had a large orbital mass and severe proptosis. MRI images revealed a large left orbital mass with optic nerve involvement and extension to the left maxillary sinus, pterygoid fossa and the dura in the floor of the anterior fossa. Fine-needle aspiration cytology of the mass confirmed tumor recurrence. The patient first received radiotherapy due to the inoperable mass, and the tumor was resected 1.5 month later. Microscopic study showed meningotheliomatous meningioma with extensive involvement of the optic nerve and invasion of the optic disc, sclera and choroid. The interesting aspect of this case was the aggressive behavior of the tumor with intraocular invasion, despite its benign histopathological features, which led to wide exenteration of the eye together with resection of the upper and lower lids.

The MDA-180 coagulation analyser: a laboratory evaluation.

We have evaluated the technical performance of the MDA-180 automated coagulation analyser in a working diagnostic hemostasis laboratory environment. The analyser has been on site now for over 18 months, and has undergone considerable testing. More than 22,000 samples have been processed, with over 90% of these via the MDA-180's cap-piercing facility. The instrument has been primarily assessed for its technical ease of use and continued reliability, as well as its analytical performance. The instrument has also been successfully interfaced to, and used with, our Laboratory information (CERNER PATHNET) system. A major feature of our evaluation has been an assessment of the MDA-180's ability to perform assays currently performed using alternative methodology or instrumentation (eg; ELISA methodology or the Coagamate-X2 and ACL-300R instruments), as well as its potential to streamline the technical performance of some of these assays. We have co-evaluated the following assays: PT/INR, APTT, TT, Fibrinogen, Protein C, ATIII, Factors II, V, VII, VIII, IX, X, XI, and XII, Lupus anticoagulant (dRVVT), and heparin (alpha Xa). In addition, a number of different reagents (particularly for PT and APTT assays) have been tested on the instrument. Intra-assay and inter-assay variation appears to be remarkably low (five different plasmas tested: PT: 0.6 to 1.3% and 0.5 to 1.3% respectively; APTT: 0.7 to 3.2% and 0.6 to 3.6% respectively; single day analysis). Other comparative assessment data typically showed good correlation to existing test assay systems. A review of other features which may enhance or detract from the instrument's worth in a given hemostasis laboratory is also presented. In summary however, we conclude that the instrument is reliable, easy to use and capable of fast sample through-put.

Laboratory assessment of von Willebrand factor: differential influence of prolonged ambient temperature specimen storage on assay results.

The laboratory assessment of von Willebrand factor (VWF) is typically performed at specialist laboratory sites, particularly when performed as a battery of laboratory tests in a thorough workup for the diagnosis of von Willebrand's disease (VWD). In these cases, specimens could derive from a variety of off-site sources, including smaller laboratories, and general clinical practitioners. Because of the potential for lack of control by the specialist laboratory over the method of specimen handling and transport from these sources, and recent VWF methodological advances, we investigated the effect of prolonged ambient temperature specimen storage on laboratory assay results. Thus, specimens were collected from 10 separate individuals, and each variably processed to provide an ideal ('control') plasma specimen, and additional specimens that were then stored at ambient temperature for up to 7 days. Specifically, specimens were stored either as whole blood, or as separated plasma, and VWF tested in isolated plasma, post 24 h, post 48 h and post 7 days storage. Three separate laboratory assays for VWF were performed; (i) a standard 'antigen' (antisera-ELISA-based) assay (VWF:Ag), (ii) a standard ristocetin-dependent-platelet-agglutination procedure (VWF:RCof) and (iii) a more recently described ELISA-based functional collagen-VWF binding assay (VWF:CBA). Results can be summarized as follows, (i) Plasma storage: there was no (statistically significant) change in VWF:Ag or VWF:RCof assay results over the 7-day storage period; however, there was a small but statistically significant fall (P= 0.009) in VWF:CBA assay results after 7 days storage of plasma. (ii) Whole blood storage: there was no (statistically significant) change in VWF:Ag, VWF:CBA or VWF:RCof assay results over the 7-day storage period, although the data suggested a trend towards increasing VWF:Ag over time. As a result of the change in assayed VWF:CBA following prolonged plasma storage, a similar small but statistically significant (P= 0.009) change (increase) in the VWF:Ag to VWF:CBA ratio was observed. This ratio has previously been determined to be useful in the differential diagnosis of VWD subtypes, with high VWF:Ag to VWF:CBA ratios potentially indicative of Type 2 VWD. Fortunately, the absolute magnitude of the altered ratio following prolonged plasma storage is unlikely in practice to affect the diagnosis of VWD in most testing cases. Nevertheless, there will be occasional borderline normal cases in whom the change in VWF:CBA, or in the calculated VWF:Ag to VWF:CBA ratio, may otherwise influence a clinical diagnosis of VWD. Caution is therefore suggested in the interpretation of laboratory-derived VWF data, particularly if the specimen is derived as an off-site referral.

Filtered plasma as a potential cause of clinical misdiagnosis: inappropriate testing in a haematology laboratory.

We have identified situations in which filtered plasma is provided to the laboratory for combined assessment of lupus anticoagulant, as well as other diagnostic haemostasis laboratory procedures. On the basis of laboratory investigation, however, we report that significant errors in test result interpretation can arise should this occur and depending on the specimen processing procedure, and whether filtered plasma is used for multiple assays. Citrated plasma samples were obtained from 12 normal individuals and a portion of each sample filtered using a standard 0.22 micron filter. Small volumes were frozen for later analysis. We could detect a statistically significant difference (P < 0.01) between filtered plasma and non-filtered plasma in most test results. Most notable were changes in the APTT, fibrinogen, FVIII and vWF, where results often fell outside the normal reference range of the assay. Such assay results closely mimic those obtained with type 2 von Willebrand's disease (vWD) patients, thus should filtered plasma unknowingly be tested for vWF, a wrong conclusion of type 2 vWD could easily arise. Assay results for other parameters may similarly draw incorrect conclusions, such as mild haemophilia A and dysfibrinogenaemia. In summary, we report that following filtration not only are a variety of coagulation test results altered, but reduced plasma levels of some coagulation factors could potentially lead clinicians incorrectly to diagnose congenital or acquired deficiencies or defects. We recommend that laboratories note that (other than for lupus anticoagulant) filtered plasma is not appropriate for the coagulation laboratory, and that any abnormal haemostasis test result following such combined testing be considered a potential artifact and independently repeated to confirm any putative abnormality prior to drawing any clinical conclusions.

The murine monoclonal antibody, 14A2.H1, identifies a novel platelet surface antigen.

A murine monoclonal antibody 14A2.H1, raised against acute myeloid leukaemia cells, identifies a previously undescribed 27 kDa platelet surface glycoprotein which is expressed at low copy number (10(3)/platelet). MAb 14A2.H1 caused aggregation of platelets which was dependent on Fc gamma RII. Binding of the antibody to platelets was not altered by activation by thrombin or phorbol ester. In haemopoietic cell populations the antibody bound to megakaryocytes, monocytes (weakly), several myeloid leukaemic cell lines and fresh myeloid leukaemic blasts from some patients. Lymphocytes, lymphoid cell lines, neutrophils and haemopoietic progenitor cells were negative. Expression of the antigen was not restricted to haemopoietic cells as epithelial cells in tonsillar crypts and endothelial cells were positive.

An improved method for measuring plasma glycocalicin in the investigation of causes of thrombocytopaenia.

Measurement of the plasma concentration of glycocalicin, the extracellular portion of platelet glycoprotein Ib, should prove to be clinically useful in the investigation of causes of thrombocytopaenia and as an indirect method of determining platelet lifespan. We describe an immunoradiometric method for the measurement of glycocalicin in plasma using two murine monoclonal antibodies. The assay has good reproducibility with coefficients of intra- and inter-assay variation of 5.4% and 7.0% respectively, requires standard laboratory skills only and, after overnight coating of the wells, enables analysis of multiple samples in approximately 4 h. With citrated plasma the result of the assay does not appear to be affected by one cycle of freeze-thaw, nor was there any observed difference in result between platelet-poor plasma (PPP) prepared by centrifugation at 1100 g for 15 min and plasma that was confirmed to be platelet-free. The plasma concentrations of citrate and ethylenediaminetetraacetate were found to affect the result of the assay thus making it important that only samples with the same type and similar concentration of anticoagulant be compared and that standards should be diluted in glycocalicin-depleted plasma with the same concentration of these anticoagulants as the unknowns.

Adrenocorticotropin binding sites in rat cardiac tissue.

Using the ACTH analog [125I-Tyr23,Phe2,Nle4] ACTH(1-24), the existence of specific binding sites for ACTH in atrial membrane preparations was demonstrated. The dissociation constants (Kd), determined by Scatchard analysis were not significantly different for membrane preparations of adrenal gland or atrial tissue (being 6.40 x 10(-12)M and 8.86 x 10(-12)M respectively). No binding was observed to membrane preparations from kidney or lung. While the binding of the ACTH(1-24) analog to atrial membranes was inhibited by ACTH(1-24), it was not affected by norepinephrine or epinephrine. It was proposed that the ACTH(1-24) analog may bind to sites located on the adrenergic nerve endings associated with the cardiac tissue, and that such binding would interfere with the neuronal reuptake of the catecholamines.

Effect of circadian rhythm on the neuronal uptake and sensitivity to the inotropic action of norepinephrine by rat atria.

The circadian rhythm for plasma corticosterone was determined. Animals were then killed at times corresponding to high and low periods of the circadian rhythm in plasma corticosterone. Myocardial sensitivity to norepinephrine was measured at these time periods as the ED50 of the catecholamine, obtained using electrically driven rat atria. The uptake of 3H-norepinephrine by spontaneously beating atria was also measured at both time periods. A circadian variation in the uptake of 3H-norepinephrine by the rat atria was observed. This variation in uptake was associated with a variation in plasma corticosterone, but was not associated with any change in myocardial sensitivity to norepinephrine.

Effect of (1-24)adrenocorticotrophin on the uptake of 3H-norepinephrine by the rat atria.

Spontaneously beating rat atria were incubated with 3H-norepinephrine both in the presence and absence of (1-24)ACTH. A significant reduction in the uptake and retention of radioactivity was found in atria pretreated with (1-24)ACTH. A kinetic study of the uptake process showed similar Km values for both the control (24.1 x 10(-8) M) and (1-24)ACTH pretreated (22.2 x 10(-8) M) groups, but a significantly different Vmax. The Km values were similar to that reported for the neuronal reuptake process (Uptake 1). It was concluded that the ACTH-induced enhanced myocardial sensitivity to catecholamines previously reported, could be explained in part on the basis of an inhibition of neuronal uptake by (1-24)ACTH. The inhibition of neuronal uptake by (1-24)ACTH was dose-dependent.

Effects of caffeine administered during pregnancy on fetal development and subsequent function in the adult rat: prolonged effects on a second generation.

Caffeine, when administered in moderate (30 mg/kg X d) or high (60 mg/kg X d) doses during pregnancy, was shown to cause significant fetal growth retardation of both sexes. Mortality rate at or soon after birth was significantly higher and litter size significantly lower in the litters treated with 60 mg. The subsequent growth rates were also affected. The experimental pups grew more slowly, with growth plateauing at the same age resulting in smaller adults. The male offspring when subjected to short-term stress (one session) in adulthood showed an intact emergency response, demonstrating an adequate ability to react to a sudden environmental change. A significant decrease in 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity, and consequent reduction in testosterone biosynthesis, in the fetal testes at d 18 and 20 of gestation was also found for both doses of caffeine. Low 3 beta-HSD activity persisted to adulthood in the group receiving 60 mg. Lingering effects were observed in a second litter bred 8 wk after the discontinuation of caffeine consumption. In this second breeding, the offspring of both sexes from both caffeine doses were born significantly smaller when compared to the controls. Persistent effects of caffeine were also found in second-generation rats bred from females who were exposed to caffeine in utero. The pups of both sexes were born significantly heavier after a significantly longer gestation. The subsequent growth did not differ from that of the controls. It was suggested that a changed genetic program in the ovarian germ cells of the first generation and/or a changed uterine environment in the second generation may be implicated.