Low-dose intra-arterial thrombolysis in the treatment of phlegmasia caerulea dolens

Three patients with phlegmasia caerulea dolens treated successfully by low-dose intra-arterial thrombolysis are presented. In all patients a rapid improvement was observed and amputation avoided. The risk of pulmonary embolus was reduced by the use of a retrievable vena cava filter in one patient and thrombolytic therapy in the presence of a previously inserted cava filter in the other two.     

Rt-PA thrombolysis in the treatment of massive pulmonary embolism

BACKGROUND: Research on psychiatric morbidity among patients with dermatological diseases generally focuses on outpatients and questionnaire-based surveys. The aim of this study was to determine the prevalence and nature of psychiatric morbidity among dermatological inpatients with diagnosis being made by psychiatric interview, and ascertain whether demographic and clinical details in dermatological inpatients with psychiatric morbidity differed from those without it. METHODS: Charts of all inpatients admitted by the dermatology department between 1 January 1991 and 31 July 1995 were analysed for socio-demographic data, clinical features, treatment and course in hospital. For those patients who were referred to a psychiatrist, all records of the psychiatric consultation were obtained and analysed. RESULTS: A total of 1073 patients were admitted during the study period. Ninety-eight patients (9%) were diagnosed to have a psychiatric illness. Patients with psychiatric illness were likely to have had more admissions and longer duration of hospital stay. The most common psychiatric diagnoses were depressive episodes (34%) and adjustment disorders (29%). The highest rates of psychiatric morbidity were found among patients with chronic urticaria, exfoliative dermatitis and sexually transmitted diseases, including human immunodeficiency virus infection. The prevalence of psychiatric disorders was significantly higher in those who had received long term (more than six weeks) treatment with high-dose steroids (more than 1 mg/kg body weight of prednisolone). CONCLUSION: Some dermatology inpatients have psychiatric morbidity, which affects the course of the dermatological condition as well as the duration of hospitalization. The availability of psychiatric consultation at dermatology clinics and regular liaison between psychiatrists and dermatologists are essential for appropriate management.     

Improvement in the treatment of acute myocardial infarct by the establishment of a thrombolysis unit in a cardiology servic

INTRODUCTION AND OBJECTIVES: Lack of available beds in the coronary care unit, makes time to thrombolysis still too long. Although fibrinolytic therapy is administered in the emergency department in most hospitals, mean in-hospital delay continues to be long. Our purpose was to improve the treatment of these patients and to evaluate if this delay could be shortened by creating a thrombolysis unit for the treatment of patients with acute myocardial infarction. METHODS: A thrombolysis unit in the cardiology department was set up to treat patients with acute myocardial infarction who couldn't be admitted directly in the coronary care unit because of lack of available beds. Time to treatment in both groups of patients were compared. RESULTS: Two hundred twenty-five patients with acute myocardial infarction and ST-segment elevation were included: 86 (38%) of them were admitted to the thrombolysis unit and the other 139 (62%) to the coronary care unit. There were no differences in baseline characteristics or in the pre-hospital delay between both groups. Time from hospital admission to thrombolysis was 59 minutes in patients treated in the thrombolysis unit versus 70 minutes in those treated in the coronary care unit (p < 0.001), and time from the admission to both units to fibrinolytic therapy was of 20 minutes versus 30 minutes respectively (p < 0.0001). There were no differences between both groups in the incidence of complications. CONCLUSIONS: In-hospital delay in thrombolysis remains too long. Implementation of a thrombolysis unit in the cardiology department shortens this delay and offers the possibility to treat patients with acute myocardial infarction at least as well as in the coronary care unit, without dependence on the availability of free beds in this unit.     

Comparative results of thrombolysis treatment with rt-PA and urokinase: a pilot study

AlphaT3-1 cells showed a slope resistance of 1.8 Gomega. The cell membrane surface was not smooth and a scanning electron micrograph showed a complex structure with blebs and microvilli like projections. The cells showed spontaneous fluctuations at zero current resting membrane potential and hyperpolarization increased the amplitude of membrane potential fluctuations. The amplitude of membrane potential fluctuations at hyperpolarized membrane potential was attenuated on application of TTX to the bath solution. The potential at which half steady state inactivation of isolated sodium current occurred, was at a very hyperpolarized potential (-95.4 mV). The study presented in this paper shows that the voltage gated sodium channels contribute to the increase in the amplitude of electrical noise with hyperpolarization in alphaT3-1 cells.     

Endothelial dysfunction following thrombolysis in vitro

OBJECTIVES: Thrombolytic therapy is frequently used to manage vascular graft thrombosis. However, long-term patency after thrombolysis remains poor. The purpose of this study was to characterise the morphological and functional response of endothelial cells (EC) exposed to a thrombus and subsequently lytic therapy. METHODS: Human EC were exposed to human whole blood thrombus for 2, 6, 12, and 24 h. The thrombus was lysed with urokinase. Cell morphology was studied with electron microscopy. Northern blot analyses were performed with human c-DNA probes for endothelin-1, thrombomodulin, tissue factor, tissue plasminogen activator, plasminogen activator inhibitor, and triose phosphate isomerase. RESULTS: EC retraction occurred for each period of incubation. Thrombomodulin expression was increased 2.2-fold at 6 h and 2.4-fold at 24 h. t-PA expression was depressed proportionally to the duration of thrombus exposure. PAI and TF expression transiently increased 1.5-fold at 2 h of exposure and returned to baseline at 6 h. Endothelin expression remained unchanged. CONCLUSIONS: Except for a transient increase in TF expression and reversal of the tPA/PAI ratio, EC exposed to thrombus do not appear to become actively procoagulant. The increase in TM expression may reflect enhanced thromboresistance. However, EC retraction may be responsible for an increase thrombogenicity of saphenous vein graft after thrombosis and Urokinase therapy.     

Reocclusion: the flip side of coronary thrombolysis

Since the introduction of thrombolytic therapy for acute myocardial infarction, the incidence of coronary artery reocclusion has been intensively studied. Also, the prediction and diagnosis of reocclusion by angiographic and clinical variables, as well its invasive and pharmacologic prevention, have gained much attention. By angiographic definition, reocclusion requires three angiographic observations: one with an occluded artery, one with a reperfused artery and a third for the assessment of subsequent occlusion (true reocclusion). Since the introduction of early intravenous reperfusion therapy, most studies use only two angiograms: one with a patent and one with a nonpatent infarct-related artery. A search for all published reocclusion studies revealed 61 studies (6,061 patients) with at least two angiograms. The median time interval between the first angiogram after thrombolysis and the second was 16 days (range 0.1 to 365). Reocclusion was observed in 666 (11%) of 6,061 cases. Interestingly, the 28 true reocclusion studies showed an incidence of reocclusion of 16 +/- 10% (mean +/- SD), and the 33 studies with only two angiograms 10 +/- 8% (p=0.04), suggesting that proven initial occlusion of the infarct-related artery is a risk factor for reocclusion after successful thrombolysis. The other predictors for reocclusion are probably severity of residual stenosis of the infarct-related artery after thrombolysis and perhaps the flow state after lysis. Reocclusion is most frequently seen in the early weeks after thrombolysis. The clinical course in patients with reocclusion is more complicated than in those without this complication. Left ventricular contractile recovery after thrombolysis is hampered by reocclusion. Routine invasive strategies have not been proven effective against reocclusion. In the prevention of reocclusion, both antiplatelet and antithrombin strategies have been tested, including hirudin and hirulog, but the safety of these agents in thrombolysis is still questionable. Thus, reocclusion after thrombolysis is an early phenomenon and is more frequent after proven initial occlusion of the infarct-related artery. Reocclusion can be predicted by angiography after thrombolysis. Because reocclusion is detrimental, strategies to prevent it should be developed and carried out after thrombolytic therapy for acute myocardial infarction as soon as they are deemed safe.     

Mechanical thrombolysis with the Amplatz thrombectomy catheter

The authors describe a rare case of rhinocerebral mucormycosis. This is an acute, suppurative mycosis with poor prognosis. It has a particular affinity for rhinocerebral tissue and less frequently affects pulmonary tissue. Mucormycosis affects immunosuppressed patients and more than 75% of the cases involve patients suffering from acidosis, especially diabetic ketoacidosis. One characteristic feature is that the blood vessels are flooded causing thromboses, infarction and emboli. The disease is spread through the blood vessels or by expansion. The first clinical symptoms can be confused with an early stage of acute sinusitis with mucosanguineous rhinorrhea, facial tumescence and pain. In 50% of the cases there is rhinocerebral and orbital involvement. If the disease remains untreated it can prove fatal in 10 to 14 days. Effective treatment relies on an early diagnosis and prompt administration of intravenous amphotericin B as well as avulsion of the necrotic areas. To date only 200 cases of this severe pathology have been described. The present work is an attempt to throw further light on this disorder.     

Role of pulse spray thrombolysis in acute ischemia of the extremities--comparison of results with the low dose technique of local thrombolysis, embolectomy and thrombectomy

BACKGROUND: The reported mortality of patients suffering from acute limb ischemia is in the range of 10% to 30%, as is the incidence of amputation in the survivors. MAIN PURPOSE: The evaluation of the pulse spray thrombolysis (PST) role in the treatment of acute extremity ischemia originating from thrombosis or embolism of native artery or bypass graft. The comparison of PST with low dose technique thrombolysis (LD), thrombectomy (TE) and embolectomy (EE). METHODS: Ninety nine consecutive patients were evaluated during a two year interval (1994-1996). PST, resp. LD, TE and EE were the method of choice in 22, resp. 11, 35 and 31 patients of average age 58.3 +/- 13.7; resp. 60.0 +/- 8.9; 74.2 +/- 11.7; 76.9 +/- 9.3 years. The native artery was occluded in 15 (68.2%), resp. 8 (72.7%), 31 (88.6%) and 30 (96.8%) patients with PST, resp. LD, TE and EE treatment. The vascular reconstruction was occluded in the rest of the cases. The lower limb extremity arteries were occluded in 20 (90.9%) of patients indicated for PST, 10 (90.9%) for LD, 33 (94.3%) for TE and 26 (83.9%) for EE. The contraindication for local fibrinolysis was severely ischemic limb in which viability was imminently threatened. RESULTS: PST was successful in 19 (86.4%), LD in seven (63.4%), TE in 13 (37.1) and EE in 27 (87.1%) patients. The failure of procedure required amputation in one patient (4.5%) with PST, one (9.1%) with LD, nine (25.7%) with TE-p < 0.001 and two (6.5%) with EE. The mortality was 4.5% (one patient), resp. 0%, 28.6% (10 patients)-p < 0.001 and 3.2% (one patient) in PST, resp. LD, TE and EE. The long term results were better if the successful local fibrinolysis was combined with percutaneous transluminal angioplasty (PTA), stent implantation or small vascular reconstruction. CONCLUSION: PST is the method of choice in the treatment of thrombotic or embolic occlusion of native artery or bypass graft in condition of good limb viability where there is no danger of time delay. EE is indicated in limb embolism where the viability of extremity is threatened. Thrombectomy alone has no place in the treatment of artery or bypass graft thrombosis.     

Determination of cardiac troponin-I in prediction of thrombolysis

Acute myocardial infarction (AMI) is a disease with high morbidity and mortality. Diagnosis of AMI using common methods (classical biochemistry, ECG) fails even in the fifth part of patients so that other noninvasive diagnostic methods are preferred. Recently, the biochemical analysis has been restored in the case of AMI diagnostics and also in prediction of coronary reperfusion after administration of a fibrinolytic agent. A suitable markers of AMI diagnostics is a combination of myoglobin and cardial troponin-I which is reported as a marker with high specificity and sensitivity. To determine coronary reperfusion, the examination of cardial troponin-T and CK-MB mass is recommended. In the literature, there exist isolated papers dealing with dynamics of cTn-I suitable for prediction of coronary revascularization. However, these papers do not report any adequate algorithm and subsequently mathematical differences between successful thrombolysis and failing thrombolysis. Therefore the aim of our study was to describe dynamics of cTn-I changes in AMI patients treated by thrombolysis. The study comprised of 8 AMI patients with delay from the occurrence of pains to fibrinolysis application under 4 hours (delay 4 hrs). These probands were examined for concentration of cTn-I and CK-MB mass in 3-hour intervals in the first 48 hours after admission to the clinic and further in 6-hour intervals from the hour 48 to the hour 90 after admission. All probands had a successful reperfusion (estimated using CK-MB peak, in 4 patients reperfusion was verified by subsequent coronarography). However, a simple mathematical prediction of coronary reperfusion after acute myocardial infarction by means of cTn-I dynamics determination is not possible due to relatively low cTn-I differences in individual analyses (CK-MB mass analysis shows more significant differences). Thus, in order to determine coronary revascularization, we recommend to use common analyses of dynamics of cTn-T or CK-MB mass.     

Low-frequency ultrasound penetrates the cranium and enhances thrombolysis in vitro

OBJECTIVE: Refinements of treatment methods are sought to rapidly reduce the volume of intracranial clots and to decrease patient exposure to possible complications of thrombolytic therapy for intracranial hematomas. We assessed the possibility of adding ultrasonication using model systems including human blood clots and temporal bone in vitro. METHODS: The transmittance of ultrasound through temporal bone obtained at autopsy was compared between the frequencies 211.5 KHz and 1.03 MHz, using a meter to determine the power delivered. The frequency 211.5 KHz was chosen to assess the ultrasound effect on the weight of 24-hour-old clots prepared from human blood after exposures at 37 degrees C to 2 mg/ml urokinase with no additional treatment, ultrasound, or agitation during an interval of up to 12 hours. At these times, fibrin degradation products also were measured. RESULTS: The transmittance of low-frequency ultrasound (211.5 KHz) through temporal bone was approximately 40%, which is four times higher than that of high-frequency ultrasound (1.03 MHz). Ultrasound but not agitation significantly increased clot lysis (140% of lysis with urokinase alone), with correspondingly increased fibrin degradation products. CONCLUSION: We conclude that low-frequency ultrasound transmits well through human temporal bone and enhances thrombolysis in vitro. Clinically, this method may be promising for reducing dosages of thrombolytic agents and shortening the period of clot removal.     

Ultrasound enhanced thrombolysis in experimental retinal vein occlusion in the rabbit

Live virus vaccines have in many cases proven to be an extremely effective tool for the prevention of viral diseases. However, the production of conventional live vaccines in eukaryotic cell cultures has many disadvantages, including the potential for contamination with adventitious agents and genetic alterations during propagation, making it necessary to do extensive testing before distribution. Based on results obtained with a flavivirus (tick-borne encephalitis virus) in an experimental animal system, we propose a novel live attenuated virus vaccination strategy consisting of the application of in vitro-synthesized infectious RNA instead of the live virus itself. When administered using the GeneGun, less than 1 ng of RNA was required to initiate replication of virus that was attenuated by a specifically engineered deletion and this induced a protective immunity in laboratory mice. Because this approach uses RNA, it does not have the potential drawbacks of DNA vaccines and thus combines the advantages of conventional live virus vaccines (for example, mimicking natural infection and inducing long-lasting immunity) with those of nucleic acid-based vaccines (for example, ease of production without a requirement for eukaryotic cell culture, stability and purity).     

Local intra-arterial thrombolysis in acute ischemic stroke

BACKGROUND AND PURPOSE: We performed a retrospective analysis of the prognostic factors in patients treated with local intra-arterial thrombolysis (LIT). The purpose of this study was to evaluate the safety and efficacy of LIT using urokinase in patients with acute ischemic stroke of the anterior or posterior circulation and to determine the influence of clinical and radiological parameters on outcome. METHODS: Forty-three patients were treated with LIT using urokinase (median dose, 0.75x10(6) IU). The median National Institutes of Health Stroke Scale (NIHSS) score at hospital admission was 18 (range, 9 to 36). Nine patients had occlusions of the internal carotid artery (ICA), 23 of the middle cerebral artery (MCA), 1 of the anterior cerebral artery, and 10 of the basilar artery (BA). Outcome was assessed after 3 months and classified as good for Rankin Scale (RS) scores of 0 to 3 and poor for RS scores of 4 or 5 and death. RESULTS: Nine patients (21%) recovered to RS scores 0 or 1, 17 (40%) to scores of 2 or 3, and 7 (16%) to scores of 4 or 5. Ten patients (23%) died. Outcome was good in 17 patients (80%) with MCA occlusions, in 3 patients (33%) with ICA, and in 5 patients (50%) with BA occlusions. Good outcome was associated with an initial NIHSS score of <20 (P<0.001), improvement by 4 or more points on NIHSS score within 24 hours (P=0.001), and vessel recanalization (P=0.02). Recanalization was more likely if LIT was started within 4 hours (P=0.01). Symptomatic cerebral hemorrhage occurred in 2 patients (4.7%). CONCLUSIONS: LIT was most efficacious in patients with MCA and BA occlusions when the initial NIHSS score was less than 20 and when treated within 4 hours. It is of limited value in patients with distal ICA occlusions.     

Endovascular thrombolysis in deep cerebral venous thrombosis

We present two cases of acute thrombosis of the internal cerebral veins, vein of Galen, and straight sinus without sagittal sinus involvement. Both patients had hydrocephalus and severe edema of the basal ganglia and thalami, one with hemorrhagic infarction of the thalamus. Because both patients rapidly deteriorated to a comatose state, endovascular thrombolysis was performed with urokinase infusion of the deep venous structures. Thrombolysis was continued until a patent channel with brisk flow in the venous structures was achieved. Both patients survived with minimal neurologic deficits.