Comparison of urokinase, alteplase, and reteplase for catheter-directed thrombolysis of deep venous thrombosis

PURPOSE: To compare the efficacy, safety, and costs associated with catheter-directed thrombolysis with urokinase (UK) and the recombinant agents alteplase (tissue plasminogen activator [TPA]) and reteplase (recombinant plasminogen activator [RPA]) in the treatment of symptomatic deep vein thrombosis (DVT). MATERIALS AND METHODS: The authors conducted a retrospective analysis on 74 patients (82 limbs) who underwent treatment for DVT. Thrombosed extremities were treated with either urokinase with therapeutic heparin dosing (UK group; 38 limbs), alteplase with subtherapeutic heparin dosing (TPA group; 32 limbs), or reteplase with subtherapeutic heparin dosing (RPA group; 12 limbs). Infusion times, dosages, drug costs, success rates, and complications were compared among the groups. RESULTS: Gender, age, disease location, duration of symptoms, and use of additional interventional therapies did not differ statistically among the three cohorts. Median hourly infused doses, total doses, infusion times, drug costs, and success rates per limb were: UK, 11.3 (10(4)) U/hour, 4.361 million U, 40.6 hours, US dollars 6577, 97.4%; TPA, 0.57 mg/hour, 21.6 mg, 30.8 hours, US dollars 488, 96.9%; RPA, 0.74 U/hour, 21.4 U, 24.3 hours, US dollars 1787, 100.0%. Major and overall complication rates were: UK, 5.3% and 10.5%; TPA, 3.1% and 12.5%; RPA, 8.3% and 16.7%. Infusion times, success rates, and complications were not statistically different among the three groups. Alteplase and reteplase were significantly less expensive than urokinase (P <.001 and P <.01, respectively). CONCLUSION: Catheter-directed thrombolysis for the treatment of DVT is safe and effective, regardless of the agent used. However, the new recombinant agents are significantly less expensive than urokinase.     

Relationship between processes of care and coronary bypass operative mortality and morbidity

BACKGROUND: Information is limited regarding the effects of processes of care on cardiac surgical outcomes. Correspondingly, many recommended cardiac surgical processes of care are derived from animal experiments or clinical judgment. This report from the VA Cooperative Study in Health Services, "Processes, Structures, and Outcomes of Cardiac Surgery," focuses on the relationships between 3 process groups (preoperative evaluation, intraoperative care, and supervision by senior physicians) and a composite outcome, perioperative mortality and morbidity. METHODS: Data on 734 risk, process, and structure variables were collected prospectively on 3,988 patients who underwent coronary artery bypass grafting at 14 VA medical centers between 1992 and 1996. Data reduction was accomplished by examining data completeness and variation across sites and surgeon, using previously published data and clinical judgment. We then applied multivariable logistic regression to the 39 remaining processes of care to determine which were related to the composite outcome after adjusting for 17 patient-related risk factors and controlling for intraoperative complications. RESULTS: Our first analysis showed several measures of operative duration, the use of inotropic agents, transesophageal echo, lowest systemic temperature, and hemoconcentration/ultrafiltration, to be powerful predictors of the composite outcome. Because the use of inotropic agents and operative duration may be related to an intermediate outcome (eg, intraoperative complications), we performed a second analysis omitting these processes. The use of intraoperative transesophageal echo and hemoconcentration/ultrafiltration remained significantly associated with an increased risk of an event (odds ratios 1.60 and 1.36, respectively). CONCLUSIONS: Our results viewed in the context of past studies suggest the possibility that inotropic use, TEE, and hemoconcentration/ultrafiltration may have adverse effects on operative outcome. Further evaluation of these processes of care using observational data, as well as randomized trials when feasible, would be of interest.     

Neural bases of cognitive ERPs: more than phase reset

Up to now, two conflicting theories have tried to explain the genesis of averaged event-related potentials (ERPs): Whereas one hypothesis claims that ERPs originate from an event-related activation of neural assemblies distinct from background dynamics, the other hypothesis states that ERPs are produced by phase resetting of ongoing oscillatory activity. So far, this question has only been addressed for early ERP components. Late ERP components, however, are generally thought to represent superimposed activities of several anatomically distinct brain areas. Thus, the question of which mechanism underlies the genesis of late ERP components cannot be easily answered based on scalp recordings. In contrast, two well-investigated late ERP components recorded invasively from within the human medial temporal lobe (MTL) in epilepsy patients, the so-called MTL-P300 and the anterior MTL-N400 (AMTL-N400), are based on single source activity. Hence, we investigated whether the MTL-P300 and the AMTL-N400 are based on an event-related activity increase, a phase reset of ongoing oscillatory activity or both. ERPs were recorded from the hippocampus and rhinal cortex in subjects performing a visual oddball paradigm and a visual word recognition paradigm. With wavelet techniques, stimulus-related phase-locking and power changes were analyzed in a frequency range covering 2 to 48 Hz. We found that the MTL-P300 is accompanied by both phase reset and power increase and that both effects overlap partly in time. In contrast, the AMTL-N400 is initially associated with phase locking without power increase and only later during the course of the AMTL-N400 we observed an additional power increase. In conclusion, both aspects, event-related activation of neural assemblies and phase resetting of ongoing activity seem to be involved in the generation of late ERP components as recorded in cognitive tasks. Therefore, separate analysis of event-related power and phase-locking changes might reveal specific insights into the mechanisms underlying different cognitive functions.     

Proximale Protektionssysteme beim Karotisstent

Controversies as to whether or not a protection device should be used in carotid artery stenting exist. Currently three temporary cerebral protection devices are being used. These are devices with distal balloon occlusion or filtration baskets and proximal occlusion devices with flow reversal in the internal carotid artery. This article focuses on flow reversal systems and aims to give some advice as to which patients could benefit from their use.     

Disease severity at time of referral for pediatric failure to thrive and obesity: time for a paradigm shift?

The percent of ideal body weight at first visit to pediatric referral clinics was compared by chart review between patients with failure to thrive and obese patients. Results indicated that underweight children were mildly underweight, whereas the overweight children were severely so. In primary care settings, underweight children may be referred more aggressively than overweight children.     

Long-term survival in SCLC after treatment with paclitaxel,carboplatin and etoposide--a phase II study

PURPOSE: We evaluated the toxicity and feasibility of adding paclitaxel to a standard platinum/etoposide regimen in the first-line treatment of patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Eighty-nine patients with limited disease (LD) or extensive disease without distant metastases (ED I) were treated in this multi-centered phase II trial between April 1996 and June 1997. Paclitaxel administration (175 mg/m(2) by a 1 h intravenous infusion) was immediately followed by a 30 min infusion of carboplatin at an area under the concentration time curve (AUC) of 5 on day 1 and etoposide 50 mg orally twice daily (bid) was given on days 2-8. Courses were repeated every 21 days. Patients who had an objective response continued treatment for a maximum of 6 courses. RESULTS: Eighty-four patients were assessable for response. Overall response rate (RR) was 82.1% with 17.8% complete remissions and 64.3% partial remissions. Median survival for LD patients was 20.5 months with a 1 year survival rate of 71.4% and a 3 year survival rate of 21.4%. Median survival of ED I patients was 11 months with a 1 year survival rate of 31.3% and a 3 year survival rate of 3.1%. Overall median survival was 18.1 months with a 1 year survival rate of 56.8% and a 3 year survival rate of 14.8%. Median progression-free intervals were 12.3 months for patients with LD stage of the disease and 8 months with ED I stage. Grade 3/4 toxicity was primarily hematologic. Grade 3/4 leucopenia occurred in 16.0% of courses and febrile episodes were detected in 0.3% of courses. Non-hematologic toxicities were uncommon. Grade 3 GI-tract toxicities or peripheral neuropathy appeared in less than 1% of the courses. Toxicities were detected according to WHO toxicity criteria. CONCLUSION: Paclitaxel can be added at full dose (175 mg/m(2)) to a carboplatin/etoposide combination while maintaining a tolerable toxicity profile. Efficacy data, RR, progression-free interval and survival in both, extensive and limited stage patients compare favorably with other reported data. This new regimen will be further evaluated in comparison to standard regimens in a phase III trial.     

Hippocampal function and visual object processing in temporal lobe epilepsy

Limbic event-related potentials related to verbal but not to visual recognition memory have been found to be attenuated within the epileptic hippocampus of patients with temporal lobe epilepsy (TLE). To identify hippocampal contributions to visual processing and memory we recorded intracranial ERPs directly from within the epileptic and the non-epileptic hippocampus in 12 patients with unilateral TLE during a visual object decision and naming task. While the non-epileptic hippocampus differentiated reliably between real and nonsense objects, this effect was completely eliminated within the epileptic mesial temporal lobe. This finding suggests that the hippocampus proper contributes to the semantic processing of visual objects and may help to explain visual memory deficits in TLE.     

Rev-independent expression of synthetic gag-pol genes of human immunodeficiency virus type 1 and simian immunodeficiency virus: implications for the safety of lentiviral vectors

The safety of lentiviral vectors for clinical applications is still a major concern. The gag-pol expression plasmids and the lentiviral vectors used in previous studies contain homologous regions, which constitute a risk for recombination events. Synthetic gag-pol genes of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) were therefore constructed, in which the codon usage was optimized for expression in human cells without altering the amino acid sequences. The synthetic gag-pol genes allowed efficient expression of these genes in the absence of Rev and the 5' untranslated leader region. Both the HIV-1 and the SIV synthetic gag-pol expression plasmids could mediate transduction of an SIV vector into nondividing human cells with titers of about 10(6) transducing units/ml. Similar titers were obtained with a four-plasmid vector-packaging system based on HIV-1. Using a biological assay, homologous recombination events between the synthetic gag-pol expression plasmids and an SIV vector were undetectable and in comparison with a previously used gag-pol expression plasmid at least approximately 100-fold less frequent. By eliminating regions of homology and sequences involved in packaging, synthetic gag-pol genes should improve the safety profile of lentiviral vectors.     

Vegetative pyoderma gangrenosum: an unusual presentation

A 44-year-old woman presented with a 6-month history of subcutaneous nodules involving her face and shins. Her past history revealed myomatous uterus with menometrorrhagia, resulting in an iron deficiency anemia, treated by ferrum sulfate tablets. She also had diabetes mellitus type II treated by glibenclamide and metformin tablets. There was no evidence of bromide or iodide ingestion. On initial examination, several firm, tender, erythematous subcutaneous nodules, 2–4 cm in diameter, were present on the face ( Fig. 1 ) and shins ( Fig. 2 ), two with normal overlying skin. Within a few weeks, the nodule on the left shin enlarged and several superficial ulcers appeared, surrounded by purplish borders, secreting sinuses, and a vegetative exophytic surface ( Fig. 3 ). Physical examination was normal. Incisional biopsies from the ulcer margins showed pseudoepitheliomatous hyperplasia, diffuse neutrophilic infiltration with microabscess formation (Fig. .4), and the presence of a dense infiltrate composed of epithelioid cells, giant cells, and a few lymphocytes forming non-necrotizing granulomas within the dermis and subcutaneous lobules ( Fig. 5 ). Leukocytoclastic vasculitis was also present in the lower dermis. Routine blood tests and urine analysis were normal, except for a high erythrocyte sedimentation rate (120/h) and anemia with a hemoglobin level of 10 g%. The results of the following laboratory tests were found to be within normal limits: rheumatoid factor; antinuclear antibody; C3; C4; serum immunoglobulins; serum protein electrophoresis; stool for parasites and occult blood; X-ray of the chest, left shin, hands, and facial bones; isotopic bone scanning; abdominal ultrasonography; chest and

Figure 1 Open in figure viewer PowerPoint Erythematous nodule on the chin