Agreement between factor XIII activity and antigen assays in measurement of factor XIII: A French multicenter study of 147 human plasma samples.

INTRODUCTION: Factor XIII (FXIII) deficiency is a rare hemorrhagic disorder whose early diagnosis is crucial for appropriate treatment and prophylactic supplementation in cases of severe deficiency. International guidelines recommend a quantitative FXIII activity assay as first-line screening test. FXIII antigen measurement may be performed to establish the subtype of FXIII deficiency (FXIIID) when activity is decreased. METHODS: The aim of this multicenter study was to evaluate the analytical and diagnostic levels of performance of a new latex immunoassay, K-Assay® FXIII reagent from Stago, for first-line measurement of FXIII antigen. Results were compared to those obtained with the Berichrom® FXIII chromogenic assay for measurement of FXIII activity. Of the 147 patient plasma samples, 138 were selected for analysis. RESULTS: The accuracy was very good, with intercenter reproducibility close to 7%. Five groups were defined on FXIII activity level (<5% (n = 5), 5%-30% (n = 23), 30%-60% (n = 17), 60%-120% (n = 69), above 120% (n = 24)), without statistical differences between activity and antigen levels (P value >0.05). Correlation of the K-Assay® with the Berichrom® FXIII activity results was excellent (r = 0.919). Good agreement was established by the Bland and Altman method, with a bias of +9.4% on all samples, and of -1.4% for FXIII levels lower than 30%. One patient with afibrinogenemia showed low levels of Berichrom® FXIII activity but normal antigen level and clot solubility as expected. CONCLUSIONS: The measurement of FXIII antigen using the K-Assay® is a reliable first-line tool for detection of FXIII deficiency when an activity assay is not available.

Optimal management of an aneurysmal subarachnoid hemorrhage in a patient with known factor XI deficiency: a case report.

The authors report a rare case of an acute cerebral aneurysm rupture in a patient with a known factor XI deficiency. Aneurysmal subarachnoid hemorrhage (SAH) accounts for a high mortality and morbidity rate. When SAH is associated with an inherited coagulation disorder such as hemophilia C, an unexpected and possible increase in hemorrhagic stroke and increase in bleeding during surgery and in the postoperative period could lead to an extremely bad outcome. Clinical management consists of rapid correction of the coagulation disorder before undergoing any invasive intracranial procedure. Such an optimal therapeutic strategy must be under the care of a multidisciplinary medical and surgical team. Human factor XI concentrate (Hemoleven, Laboratoire Français du Fractionnement et des Biotechnologies [LFB], Les Ulis, France) was used successfully in this case report. New treatment using recombinant factor VIIa is discussed.

Postoperative thrombotic microangiopathy following radical cystectomy for bladder cancer.

This report describes the perioperative management of disseminated intravascular coagulation occurring abruptly during a planned cystectomy for non-metastatic bladder papillary carcinoma. Peroperatively, profuse bleeding and an acute decrease in blood pressure were effectively treated by blood transfusions and fresh frozen plasma. Haematological tests indicated the presence of disseminated intravascular coagulation. On the following three days, acute renal failure, peripheral disseminated intravascular coagulation-related thrombocytopenia and haemolytic anemia with schistocytes were suggestive of thrombotic microangiopathy. Treatment by plasma exchange along with haemodialysis was commenced. An aetiological work-up remained negative. After 21 days of treatment, haemodialysis and plasma exchange were stopped. Urological outcome was favourable. The one-year follow-up did not show any residual renal insufficiency and laboratory parameters returned to normal. In the absence of evidence in favour of an infectious, drug-related or immunological aetiology, we postulated that this thrombotic microangiopathy was caused by disseminated intravascular coagulation and that the tumour manipulation during the surgical procedure was the triggering factor.

Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD.

OBJECTIVE: To compare regional cerebral blood flow (rCBF) changes using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT in subjects with dementia with Lewy bodies (DLB) and AD and in normal age-matched control subjects; to examine the utility of SPECT changes in the differential diagnosis of AD and DLB. METHOD: Whole-brain SPECT scans were acquired using a single-headed rotating gamma camera (IGE CamStar XR/T) in elderly subjects with consensus criteria DLB (n = 23; mean age = 79.4 years), National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association AD (n = 50; 81.9 years), and normal control subjects (n = 20; 78.1 years) after injection with 500 MBq of 99mTc-HMPAO. Region-of-interest analysis was performed using a SPECT template registered in Talairach space, with rCBF normalized to cerebellum. RESULTS: Both DLB and AD subjects had significantly reduced rCBF in parietal and temporal regions compared with the control subjects. The AD group also showed a significant reduction in rCBF in the frontal and medial temporal regions and the DLB in the occipital areas compared with control subjects. AD and DLB groups differed only in occipital perfusion (p < 0.01). SPECT measures (occipital and medial temporal) correctly classified 69% of all subjects, with a 65% sensitivity and 87% specificity for DLB against AD and control subjects. CONCLUSION: Temporoparietal hypoperfusion on SPECT is common to both AD and DLB. Occipital hypoperfusion is more frequently seen in DLB. Although not diagnostically specific in individual cases, occipital hypoperfusion on SPECT should raise suspicion that DLB may be the cause of dementia, prompting careful search for other features of the disorder.

Does the ICD 10 classification accurately describe subtypes of borderline personality disorder?

The aim of the paper is to explore whether the division of borderline personality disorder, as described in the DSM classification, into impulsive and borderline subtypes of emotionally unstable personality disorder in the ICD classification of personality disorder, is a valid division. The self-report questionnaire responses of 288 referrals to a personality disorder service were rated on each of the eight criteria for DSM-III-R diagnosis of borderline personality disorder. Factor analysis identified two factors; factor one closely corresponds with the borderline subtype of ICD10, whilst factor two closely corresponds with the impulsive subtype of ICD10. Criteria common to both factors unstable relationships and identity confusion - were considered core features of borderline personality disorder. The pattern of occurrence of the two factors was similar to the complex binary picture described by ICD10. However there were also differences. Firstly, identity confusion is found to be a core feature of both our factors, and this does not conform to the restriction of identity confusion to the borderline subtypes in ICD10. Secondly, we found a residual pool of undifferentiated borderline patients and a small group of pure non-impulsive borderline patients who are not currently accommodated within the ICD10 emotionally unstable personality disorder. We conclude that future classifications of this disorder should accommodate four subtypes, and suggest these subtypes have implications for treatment and further research.

A voxel-based analysis of cerebral perfusion in dementia and depression of old age.

Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.

Autoantibodies directed against phospholipids or human beta 2-glycoprotein I in HIV-seropositive patients: relationship with endothelial activation and antimalonic dialdehyde antibodies.

BACKGROUND: We investigated the possible role of antiphospholipid (APA) and anti-human 2-glycoprotein I (beta2-GPI) antibodies (Ab) in thrombosis and atherosclerosis in human immunodeficiency (HIV)-positive patients, in whom they seem to be more frequent. METHODS: We measured APA and anti-beta2-GPI Ab in 58 HIV-positive patients together with markers of disease progression, circulating beta2-GPI, plasma lipids, biological markers of endothelial activation and integrity (plasma thrombomodulin, von Willebrand factor, vascular cell adhesion molecule 1) and with antimalonic dialdehyde antibodies (anti-MDA Ab). RESULTS: We found a 41% frequency of IgG APA in the HIV-positive patients. APA IgMs were rarely positive (7%), and anti-beta2-GPI IgGs were positive in 3-4% patients. There was no correlation between APA or anti-beta2-GPI Ab and the presence of opportunistic infections. Although plasma thrombomodulin, von Willebrand factor and vascular cell adhesion molecule 1 were significantly increased in the HIV-positive patients, APA was correlated only with vascular cell adhesion molecule 1, suggesting that APAs are correlated with endothelial activation but not with vascular endothelial lesions. A correlation between APA and anti-MDA IgG was demonstrated using multivariate analysis (r=0.542, P < 0.0001), suggesting a relationship between the targets of these antibodies. Finally, IgG APAs are frequent in HIV infection but are not correlated with biological markers of endothelial injury. CONCLUSION: Our results do not support a role for APA or anti-beta2-GPI in HIV-associated silent vascular endothelial damage. However, the role of these autoantibodies in clinically relevant thrombotic events should be investigated in HIV-positive patients.

Performance on the delayed word recall test (DWR) fails to differentiate clearly between depression and Alzheimer's disease in the elderly.

BACKGROUND: The differential diagnosis of early dementia of the Alzheimer's type from depression in the elderly is often made difficult by the presence of significant memory impairment in depressed patients. The Delayed Word Recall test (DWR) was developed to facilitate the early diagnosis of Alzheimer's disease. The DWR involves: (a) repeated elaborate encoding of ten separate words; (b) a filled delay; (c) delayed free recall. A recognition memory test has also been recently developed. The available evidence suggests impressive sensitivity and specificity when the DWR has been used to separate patients with early Alzheimer's disease from very well matched controls. METHODS: In the present study, the DWR was evaluated with regard to its ability to separate a group of 50 patients with early Alzheimer's disease from 50 elderly patients with major depression in a between-subjects experimental design. RESULTS: For both free recall and recognition indices, the between-group overlap was large. Using recommended cut-off scores for the detection of Alzheimer's disease, 44% of the depressed patients would have been misclassified as demented based on their free recall scores, and 48% of the depressed patients would have been misclassified on the basis of their recognition scores. CONCLUSION: We conclude that the DWR is not specific enough to clearly distinguish patients with early Alzheimer's disease from elderly patients with major depression.

Temporal lobe abnormalities in dementia and depression: a study using high resolution single photon emission tomography and magnetic resonance imaging.

OBJECTIVES: Perfusion SPECT and MRI were used to test the hypothesis that late onset depression is associated with brain abnormalities. METHODS: Forty depressed patients (DSM-III-R major depressive episode, not demented at two year follow up) were recruited who were either drug free, or on a stable dose of antidepressants for at least three weeks, as well as 22 demented patients (DSM-IIIR and NINCDS/ADRDA criteria for probable Alzheimer's disease). Patients were imaged at rest with a high resolution single slice 12 detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-exametazime (HM-PAO). Temporal lobe templates were fitted with brains pitched by 20 degrees-30 degrees. A subgroup of 41 patients (22 depressed) were also scanned using a Siemens Magnetron 1.0 Tesla magnetic resonance imager, using a FLAIR imaging sequence for the assessment of white matter hyperintensities, and a Turbo FLASH sequence for the measurement of medial temporal lobe width. RESULTS: Demented patients showed reduced perfusion, particularly in the left temporoparietal cortex. In these regions of interest, patients with late onset depression tended to have perfusion values intermediate between patients with early onset depression and demented patients. Differences in changes in white matter between demented and early and late onset depressive patients did not reach conventional levels of significance. Temporal lobe width differed between demented and depressed patients, but not between early and late onset depressed patients. Perfusion and temporal lobe width were not associated, but reductions of perfusion were associated with periventricular white matter changes. Mini mental state examination scores were associated with temporal perfusion in demented patients and with changes in deep white matter in depressed patients. Finally, severity of depressive symptoms was associated with decreased perfusion in frontotemporal and basal ganglia regions of interest. CONCLUSION: A cumulative effect of duration of illness on regional cerebral perfusion could not be confirmed. Late onset depression may show more abnormalities of deep white matter and of left temporoparietal perfusion than early onset depression, but the underlying pathology remains to be established.

Randomised controlled trial in northern England of the effect of a person knowing their own serum cholesterol concentration.

SUBJECT OBJECTIVE: To test the hypotheses that the knowledge that the serum cholesterol concentration is raised (> or = 6.5 mmol/l) will lead to a reduction in the concentration after education intervention and that the knowledge that the concentration is not raised does not lead to an increase in the serum cholesterol concentration after education intervention. DESIGN: Prospective randomised trial, with investigators blind to the randomisation. SETTING: An industrial site in Manchester, England. PARTICIPANTS: A total of 495 employees of Imperial Chemical Industries, 469 of whom completed the trial. MAIN RESULT: There was a significant reduction in the serum cholesterol concentration of those whose initial concentration was > or = 6.5 mmol/l and who were given the result. This reduction was 0.28 mmol/l greater than in the control group. The reduction was similar, however, to the increase in the serum cholesterol concentration in those whose initial concentration was < 5.2 mmol/l, regardless of whether or not they had been given the result. CONCLUSION: These results support the hypotheses, although the lack of regression to the mean in the control group with high serum cholesterol suggests that this conclusion should be treated with caution.

Electrophysiological properties of nigrothalamic neurons after 6-hydroxydopamine lesions in the rat.

Extracellular recordings were made from electrophysiologically identified nigrothalamic cells in the substantia nigra pars reticulata of anaesthetized rats. The firing rate, firing pattern and responses to striatal stimulation were investigated in normal animals and in animals in which dopamine concentration in the ipsilateral striatum was reduced by more than 90%. At relatively short times after the lesion (less than 10 days) the mean firing rate of the spontaneously active cells in the population was significantly reduced and there was an increase in the occurrence of bursting activity. There was also a significant increase in the number of silent cells, located by antidromic stimulation from the thalamus. In spite of this reduction in mean firing rate the responses of neurons to stimulation of either the ipsilateral striatum or ventromedial thalamus was much larger in cells from lesioned animals. At longer times after the lesion (more than six months) the average firing rate of the neurons had returned to normal but there was still a prevalence of bursting activity and a consequent reduction in mean inter-spike intervals. There was little evidence of the previous hyper-responsiveness to thalamic stimulation but the responsiveness to striatal stimulation was still significantly elevated.