Myosin: a noncovalent stabilizer of fibrin in the process of clot dissolution

Myosin modulates the fibrinolytic process as a cofactor of the tissue plasminogen activator and as a substrate of plasmin. We report now that myosin is present in arterial thrombi and it forms reversible noncovalent complexes with fibrinogen and fibrin with equilibrium dissociation constants in the micromolar range (1.70 and 0.94 microM, respectively). Competition studies using a peptide inhibitor of fibrin polymerization (glycl-prolyl-arginyl-proline [GPRP]) indicate that myosin interacts with domains common in fibrinogen and fibrin and this interaction is independent of the GPRP-binding polymerization site in the fibrinogen molecule. An association rate constant of 1.81 x 10(2) M(-1) x s(-1) and a dissociation rate constant of 3.07 x 10(-4) s(-1) are determined for the fibrinogen-myosin interaction. Surface plasmon resonance studies indicate that fibrin serves as a matrix core for myosin aggregation. The fibrin clots equilibrated with myosin are stabilized against dissolution initiated by plasminogen and tissue-type plasminogen activator (tPA) or urokinase (at fibrin monomer-myosin molar ratio as high as 30) and by plasmin under static and flow conditions (at fibrin monomer-myosin molar ratio lower than 15). Myosin exerts similar effects on the tPA-induced dissolution of blood plasma clots. Covalent modification involving factor XIIIa does not contribute to this stabilizing effect; myosin is not covalently attached to the clot by the time of complete cross-linking of fibrin. Thus, our in vitro data suggest that myosin detected in arterial thrombi binds to the polymerized fibrin, in the bound form its tPA-cofactor properties are masked, and the myosin fibrin clot is relatively resistant to plasmin.     

Occurrence and course of suicidality during short-term treatment of late-life depression

BACKGROUND: Elderly persons (> or =65 years) have the highest rate of suicide; still, little is known about the occurrence, course, and responsivity of suicidal ideation during treatment of depression in late life and how suicidality affects treatment response. METHODS: This study was undertaken to determine (1) how suicidal ideation changes during short-term depression treatment and (2) whether treatment response differs among 3 groups of patients based on their levels of suicidality at baseline and during treatment (those with a recent suicide attempt or current suicidal ideation [high-risk group; n = 46], those with recurrent thoughts of death [moderate-risk group; n = 143], or those with no suicide attempt, suicidal ideation, or thoughts of death [low-risk group; n = 206]). This is a secondary analysis of pooled data from 3 treatment studies of late-life major depression. Participants were 395 elderly persons with a current major depressive episode, treated as inpatients or outpatients under protocolized conditions with paroxetine hydrochloride or nortriptyline hydrochloride, with or without interpersonal psychotherapy. Changes in suicidal ideation over time, rate of responses, and time to response in each group were compared. RESULTS: Suicidal ideation decreased rapidly early in the course of treatment, with more gradual change thereafter. At the beginning of treatment, 77.5% of the patients reported suicidal ideation, thoughts of death, or feelings that life is empty. After 12 weeks of treatment, suicidal ideation had resolved in all treated patients; 4.6% still reported thoughts of death. However, 6-week (P =.001) and 12-week (P =.02) rates of response were significantly lower in high-risk patients than in low- and moderate-risk patients. High- and moderate-risk patients needed a significantly (P<.001) longer time to respond than low-risk patients (median time to response, 6 and 5 vs 3 weeks). CONCLUSIONS: While suicidal ideation resolves rapidly, the resolution of thoughts about death is more gradual. Suicidal elderly persons with depression require special attention during depression treatment because they have a lower response rate and need a longer time to respond.     

Increased prevalence of platelet glycoprotein IIb/IIIa PLA2 allele in ischaemic stroke associated with large vessel pathology

Introduction: Platelet glycoprotein IIb/IIIa is a membrane receptor with a central function in the platelet adhesion and ultimately in the thrombus formation. Two major variants of the gene encoding the IIIa subunit, called PLA1 (A1) and PLA2 (A2), have been identified in the general population. There are indications that the A2 allele can also be associated with acute thrombosis or stroke. The purpose of this study was to study the distribution of the A2 allele in different vascular subtypes of stroke disease. Materials and methods: A total of 638 consecutive patients were analyzed and classified as having large vessel pathology (n=168) or a small vessel infarct (n=210). Localization of the vascular occlusions was deducted from analysis of the magnetic resonance imaging (MRI) scan results in stroke patients. The remainder patients were listed into a mixed vascular pathology group (n=167). Patients with other or poorly characterized stroke etiology were excluded from the study (n=93). Results: In the small vessel and mixed vascular pathology groups, the PLA2 allele frequency was similar to that in the controls. By contrast, PLA2 allele frequency was approximately two-fold higher in patients with large vessel pathology (23.3%) than in the stroke-free control subjects (11.7%, p<0.0005). Multivariate logistic regression analysis of data confirmed this association with an odds ratio (OR) of 2.9 (95% confidence interval [CI]: 1.6–4.9, p<0.0005). Conclusions: These data suggest that the PLA2 allele is more frequent in brain infarcts associated with large-vessel occlusion.     

Aboral pouch with preserved duodenal passage--new reconstruction method after total gastrectomy

A new reconstruction method--the aboral pouch with preserved duodenal passage--has been introduced after total gastrectomy. After removal of the stomach, preparation of the Roux loop and construction of the esophago-jejunostomy, a jejuno-duodenostomy is performed approximately 50 cm away from the esophageal anastomosis between the Roux limb and the duodenal stump. Right below this second anastomosis, the Roux limb is closed with a stapling device to provide a unidirectional food passage through the duodenum. The aboral pouch is constructed as a side-to-side anastomosis between the Roux limb under the stapled segment and the aboral end of the Y limb. The advantages of the reservoir-constructing methods and the interposition methods are combined in this new reconstruction type. Our experiences of 17 cases having undergone this reconstruction method are presented.     

The first heart-lung transplantation in a Hungarian patient with cystic fibrosis

INTRODUCTION: Progressive lung disease and respiratory insufficiency is the leading cause of early death for patients with cystic fibrosis. METHOD: Successful heart-lung transplantation was performed in the 24 years old man with cystic fibrosis for end stage lung diseases and for concomitant dilatative cardiomyopathy. RESULTS: Six months following the operation the patient returned to full-time his job, and leads an active life like other fellow-men of his age. CONCLUSIONS: The attention is called with this case report to a rarely necessary intervention available for Hungarian patients as well. The criteria of the lung transplantation in cystic fibrosis, the preoperative screening and the tasks of the postoperative care are summarised.     

Assessment of the aversion coefficient in nuclear safety in Hungary

The key elements of the optimization practice as applied to radiation protection are the monetary value of the averted person-sievert and the aversion coefficient. Determination of the monetary value of the unit averted person-sievert (as alpha(base)-parameter) in Hungary was presented in a previous paper. The estimation of this parameter was carried out by the willingness-to-pay (WTP) method associated with averted occupational exposure (at the NPP Paks/Hungary). The aversion coefficient predicts the importance of dose reduction based on the magnitude of the dose. The assessment of the aversion coefficient occurred also by means of the WTP method in the spring of 2000. Its value has been estimated on the basis of individual preferences concerning the distribution of individual exposure in nuclear safety. The results achieved by the WTP among the radiation specialists from the NPP Paks, Hungary, assessed a value for the aversion coefficient of 1.86 over the whole range of individual exposure levels. This value is a bit greater than the value obtained in France (1.7) and the higher coefficient expresses a higher priority to reduce the highest individual exposures.     

Role of SPECT scans in the diagnosis of cerebrovascular diseases

With an incidence of 200-250 in 100,000 persons year, cerebrovascular disease (CVD) is the most common neurological disorder. In most countries, CVD is the third most frequent cause of death, exceeded only by heart disease and cancer. There are roughly 5.000 new cases per year in Hungary. Additionally, it should be emphasized that there are facts suggesting a more severe population of patients with CVD compared to the analogue group in more developed countries. There are several causes of stroke, but common to all is a critical reduction in cerebral blood flow, resulting in a focal neurological deficit. Functional imaging, particularly of cerebral perfusion, should therefore have a major role to play in the management of these patients. SPECT methods are of high importance in the diagnosis of CVD and in the patients follow-up.