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Biomedical subjects

R Liesner

Publications and source records attributed to R Liesner.

29 records · Page 2Linked to original sources
PubMed1999

Performance of the platelet function analyser PFA-100 in testing abnormalities of primary haemostasis.

The PFA-100 device is a new instrument for the in-vitro testing of platelet function. Primary haemostasis is stimulated by recording the closure time taken for platelets to seal a 150 microm aperture in the centre of a membrane coated with collagen and either epinephrine or ADP. Patients with type 3 von Willebrand's disease (n = 4) all had infinitely prolonged closure times (> 200 s) with both types of cartridge. A patient with afibrinogenemia exhibited only slightly prolonged closure times of 111 and 166 s for the ADP and epinephrine membranes, respectively. Patients with Glanzmann's thrombasthenia (n = 6) and Bernard Soulier syndrome (n = 2) had grossly prolonged closure times (> 200 s) with both types of cartridges. These results confirmed that the PFA-100 system was highly dependent on normal von Willebrand factor, glycoprotein Ib and glycoprotein IIb/IIIa levels but not on plasma fibrinogen. Patients with storage pool disease (n = 6) and Hermansky Pudlak syndrome (n = 7) had prolonged closure times with the epinephrine cartridge. There was no evidence of enhanced platelet function in patients with antiphospholipid syndrome, in sickle-cell disease or thalassemia. However, ingestion of aspirin resulted in a near consistent and significant prolongation of the closure time for the epinephrine cartridge but not for the ADP cartridge in both normal subjects and patients. The test offers a reliable, reproducible, rapid and simple means of assessing high-shear platelet function in vitro.

Blood Platelets↗
PubMed1998

Flow cytometric analysis of reticulated platelets: evidence for a large proportion of non-specific labelling of dense granules by fluorescent dyes.

The labelling of platelets with thiazole orange (TO) has been utilized by various laboratories to determine the percentage of reticulated platelets within whole blood or platelet-rich plasma (PRP). A proportion of TO labelling, however, is not entirely mRNA specific and remains to be fully defined. Almost half of the total TO-positive signal within normal platelets (n = 5) was shown to be abrogated upon degranulation with 80 microM thrombin receptor activating peptide (TRAP) (P = 0.006), strongly suggesting that platelet granules are non-specifically labelling with dye. We have confirmed this hypothesis by studying TO labelling of platelets within whole blood from dense granule deficient patients, e.g. Hermansky-Pudlak syndrome (HPS) (n = 5) and storage pool disease (SPD) (n = 4). The levels of TO-positive platelets were found to be significantly lower than normal (P = 0.0003 and P = 0.0002 respectively), but not significantly different from TRAP degranulated platelets. Upon degranulation of HPS and SPD platelets there was very little further reduction in the TO signal. Incubation of normals and SPD whole blood with different concentrations of either TO or coriphosphine-O confirmed that dense granules were non-specifically labelling even at high concentrations of both dyes. These findings suggest that although TO labelling is in part RNA specific, the dense granular pool of nucleotides appears to cause a substantial amount (approximately 50%) of non-specific labelling observed under these conditions of assay. This can easily be controlled for by a degranulation step with a non-enzymatic platelet agonist such as TRAP, and may have important consequences for the eventual standardization. clinical utilization and automation of reticulated platelet assays.

Albinism, Oculocutaneous↗
PubMed1998

Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion.

Vascular occlusion has a central role in the pathophysiology of sickle cell disease (SCD) and, although there is little evidence that thrombosis alone is responsible, patients with sickle cell disease are known to have an ill-defined but increased thrombotic risk. The most serious complication of this in childhood is stroke which occurs in 7-10% of children and a further 14% have asymptomatic cerebrovascular disease (CVD) on imaging. We have performed a comprehensive profile of coagulation inhibitors and markers of thrombin generation in 96 children (83 nontransfused [NTx] and 13 transfused [Tx]) with steady-state SCD and 18 healthy sibling controls. The levels of protein S (free and total) and heparin cofactor II were reduced in both the NTx and Tx groups compared to controls and protein C and APC resistance ratios were reduced in the NTx group only. Antithrombin levels were not different from controls. Thrombin-antithrombin complexes and prothrombin fragment F1+2 were increased in both patient groups. In the NTx subgroups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD. We conclude that children with SCD have a reduction in levels of the majority of the coagulation inhibitors and increased thrombin generation in the steady-state and these are only partially reversed by transfusion. However, these abnormalities do not appear to play a primary role in the development of cerebrovascular disease.

Activated Protein C Resistance↗
PubMed1998

Inherited prothrombotic states and ischaemic stroke in childhood.

OBJECTIVE: To investigate the prevalence of currently recognised inherited prothrombotic states in a population of children with arterial stroke. METHODS: Children with arterial stroke presenting to a tertiary level paediatric neurology centre between 1990 and 1996 were investigated for inherited prothrombotic states. RESULTS: Sixty seven children with arterial stroke were investigated. Abnormalities were initially identified in 16 patients; however, only eight children (12%) had an inherited prothrombotic state. This was type 1 protein S deficiency in one patient, the factor V Leiden mutation in six, and activated protein C resistance (without the factor V Leiden mutation) in one. The prevalence of the factor V Leiden mutation was not significantly higher in children with arterial stroke (12%) than in a control population of children without thrombosis attending the same institution (5.2%; Fisher's exact test, p=0.19; difference in prevalence between patients and controls (95% confidence interval)=6.8% (-2.78% to 16.8%)). CONCLUSIONS: Currently recognised inherited prothrombotic tendencies were rarely associated with stroke in this group of children, although larger numbers of patients would be needed to confirm this. Age appropriate normal values should be used when interpreting the results of a prothrombotic screen. Prothrombotic abnormalities seen acutely are as often transient as inherited. Longitudinal assessment and family studies are required before low concentrations of an anticoagulant protein found acutely can be attributed to an inherited abnormality.

Adolescent↗
PubMed1997

Complications experienced with central venous catheters in children with congenital bleeding disorders.

The use of central venous catheters (CVC) in children with coagulation disorders allows home treatment, the use of prophylactic blood product replacement and induction of immune tolerance. Previous reports have suggested an almost complete lack of infective complications in this patient group. We reviewed 2 3 patients with bleeding disorders who have had 32 CVC inserted at this institution with a median follow-up of 27 months (range 1-92 months). There were 25 documented line-associated infections, including two subcutaneous infections at the port site, and 23 bacteraemias (one episode per 26 patient months at risk). There were 15 Gram-positive, nine Gram-negative and one mixed infection. Infections occurred in 48% of the patients. 15 CVCs were removed: one for erosion through the skin, two for line blockage and 12 for infection. Five patients with inhibitors to factor VIII suffered 14 infections in 12 lines (one per 8.3 months) whereas the 18 without inhibitors suffered 11 infections in 20 lines (one per 50 months) (P<0.03). The use of CVCs is favoured by families of children with bleeding disorders in spite of these complications, but close liaison between families and experienced staff at a Haemophilia Centre is essential to ensure that patients gain the benefits of a CVC as safely as possible.

Bacterial Infections↗
PubMed1997

Treatment of childhood and adult acute lymphoblastic leukaemia.

In the last 30 years the treatment of acute lymphoblastic leukaemia has radically changed and intensified and has resulted in improvements in the chances of cure in children to up to 70% but in adults only 30% will achieve long-term disease-free survival. Data from large therapeutic trials have determined good and poor prognostic risk factors which have been of use in planning risk-directed treatment protocols and can influence the chance of cure. However intensification of treatment has also been associated with increased toxicity and significant late effects, particularly in children. In the future it will be necessary for more international collaboration and a more uniform approach to treatment in order to achieve continued improvements in the survival from this disease. In children it will be necessary to focus efforts on improving treatment of relapsed patients: chemotherapy protocols in those with a first remission of > 36 months, or for the high-risk patients with a shorter first remission, new transplantation approaches directed towards enhancing the graft-versus-leukaemia effect are going to be of increasing importance. In adults, continued efforts will be directed towards improving first remission rates with the use of increasingly intensive chemotherapeutic protocols and growth factors. The use of unrelated donor transplantation is also likely to increase, particularly in patients with 'poor-risk' disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Pseudopyropoikilocytosis: a striking artefact.

The blood films both of patients with hereditary pyropoikilocytosis and of those with severe thermal burns are characterised by budding erythrocytes and the presence of microspherocytes. Recently, a fourth example of similar morphological features, caused by overheating of a blood specimen in a motor vehicle during transport to the laboratory, has been observed. It is important to be aware of this artefact as failure to recognise it is likely to lead to diagnostic confusion and unnecessary further testing, causing inconvenience to the patient.

Diagnostic Tests, Routine↗
PubMed1984

Intraepithelial inclusions resembling human biondi bodies in the choroid plexus of an aged chimpanzee.

Complex intracellular inclusion bodies of the Biondi type were observed in the choroidal epithelium (choroid plexus of the lateral ventricle) of a 43-year-old male chimpanzee. The specific components of these inclusions are bundles of filaments 8-15 nm in diameter, which are associated with lipid droplets and a wide variety of unidentified inclusions of differing electron density. Biondi bodies are characteristic inclusions of the choroid plexus of aged humans but have been claimed to be absent from the choroidal epithelium of senescent animals including nonhuman primates. The present finding of Biondi body-like inclusions in an aged chimpanzee underscores the usefulness of nonhuman primates as models for studies of aging, seeking to gain a better understanding of gerontological aspects of the human brain.

Animals↗
PubMed1981

Pineal complex of the clawed toad, Xenopus laevis Daud.: structure and function.

The morphological and physiological properties of the pineal complex of Xenopus laevis were investigated in larval, juvenile and adult animals. In a representative majority of adult X. laevis, the frontal organ does not display signs of degeneration. Fully differentiated frontal organs contain photoreceptors typical of the pineal complex of lower vertebrates. By means of the acetylcholinesterase (AChE)-reaction approximately 30 neurons of two different types were demonstrated in the frontal organ. The frontal-organ nerve is composed of approximately 10 myelinated and 40 unmyelinated nerve fibers. The neuropil areas of the frontal organ are generally similar to the corresponding structures of the intracranial epiphysis. The neuronal apparatus of the epiphysis cerebri of X. laevis consists of (i) photoreceptor cells, (ii) approximately 100 AChE-positive neurons, (iii) complex neuropil areas, and (iv) a pineal tract formed by approximately 10 myelinated and approximately 100 unmyelinated nerve fibers. Some of them exhibit granular inclusions indicating that pinealopetal elements may enter the pineal complex of X. laevis via this pathway. The topography of the pineal tract of X. laevis differs considerably from that in ranid species. The most conspicuous element of the plexiform zones is the ribbon synapse. The basal processes of the photoreceptor cells may be presynaptic elements of simple, tangential, dyad or triad synaptic contacts. Conventional synapses were observed only occasionally. Electrophysiological recordings revealed that the pineal complex of Xenopus laevis is directly sensitive to light. In response to light stimuli, two types of responses, achromatic and chromatic, were recorded from the nerve of the frontal organ. In contrast, the epiphysis exhibited only achromatic units. The opposed color mechanism of the chromatic response showed a maximum sensitivity at approximately 360 nm for the inhibitory and at 520 nm for the excitatory event. The action spectrum of the achromatic response of the epiphysis and the frontal organ peaked between 500 and 520 nm and showed no Purkinje-shift during dark adaptation. The functional significance of these phenomena is discussed.

Acetylcholinesterase↗