Purification and properties of heparin-releasable lipoprotein- associated coagulation inhibitor

The lipoprotein-associated coagulation inhibitor (LACI) is present in vivo in at least three different pools: sequestered in platelets, associated with plasma lipoproteins, and released into plasma by intravenous heparin, possibly from vascular endothelium. In this study we have purified the heparin-relesable form of LACI from post-heparin plasma and show that it is structurally different from lipoprotein LACI. The purification scheme uses heparin-agarose chromatography, immunoaffinity chromatography, and size-exclusion chromatography and results in a 185,000-fold purification with a 33% yield. Heparin- releasable LACI (HRL), as analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis, under reducing conditions, appears as a major band at 40 Kd and a minor band at 36 Kd. Immunoblot analysis suggests that the 36-Kd band arises from carboxyl-terminus proteolysis that occurs during the purification. HRL has a specific activity similar to that of HepG2 or lipoprotein LACI. HRL and lipoprotein LACI combine with lipoproteins in vitro while purified HepG2 LACI does not. I125-labeled HRL, injected into a rabbit, is cleared more slowly than I125-labeled HepG2 LACI, which may be due to attachment to lipoproteins in vivo. Preliminary evidence suggests that HRL is associated with vascular endothelium, possibly by attachment to glycosaminoglycans.     

The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy

A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of this enzyme by 2'-deoxycoformycin in 15 patients with hematologic malignancies. Biochemical consequences of the administration of this agent were closely monitored in erythrocytes, nucleated peripheral blood and bone marrow cells, serum, and urine. A marked rise in erythrocyte dATP was accompanied by a depletion of ATP in those patients exhibiting toxicity. Most patients excreted large amounts of deoxyadenosine but not adenosine in the urine. Serum deoxyadenosine rose in patients demonstrating a marked decrease in cell mass. The biochemical disturbances and clinical toxicity, including hepatic, renal, and conjunctival abnormalities, were usually reversible. Central nervous system toxicity, which potentially was the most serious consequence, was associated with high erythrocyte dATP/ATP ratios and high levels of cerebrospinal fluid deoxyadenosine. In patients with lymphoma and leukemia, objective responses were observed but were short- lived. Patients with chronic lymphocytic leukemia receiving weekly low doses of the drug demonstrated minimal toxicity and some efficacy. The chemotherapeutic potential o 2'-deoxycoformycin, as either a single agent or in combination with Ara-A, merits further exploration.     

Management of occult metastatic disease from salivary gland neoplasms

Evaluating salivary gland neoplasms is difficult because of the relatively low incidence of these lesions, their variable locations, and their multiple histologic cell types. Little has been reported on nodal metastases, whether manifest or occult, from these neoplasms. Ninety cases of salivary gland neoplasm are analyzed to provide a clearer understanding of the appropriate approach to occult salivary gland cervical metastases. Manifest regional metastases at the original presentation were absent in 72% (65/90). Few nodal metastases occurred after the primary tumor was controlled (2% [1/56]). Local recurrence (38% [34/90]) and distant metastases (25% [14/56]) were more common. Stage I and II disease was treated by surgical resection of the primary tumor alone; resection was combined with postoperative radiation therapy for stage III disease. Whenever the neck was entered for stage III disease, a conservative neck dissection was incorporated with the resection to reduce the postoperative irradiation field once the neck had been proved N, O histologically. Delayed nodal metastasis was treated by neck dissection alone.     

Prostaglandins and angioplasty. An experimental study in canine arteries

To prevent platelet aggregation following percutaneous transluminal angioplasty (PTA), cyclooxygenase inhibitors such as acetylsalicylic acid (ASA) and indomethacin are recommended. However, ASA blocks both the proaggregating effects of thromboxane (TXA2) and the antiaggregating and vasodilating effects of prostacyclin (PGI2). The authors measured the contractile response of dilated canine carotid arteries in situ and in vitro using an isometric force transducer. Following PTA, contraction of the arterial wall was significantly reduced (p less than 0.01). By blocking cyclooxygenase with indomethacin (3 micrograms/ml), contraction was greatly improved (p less than 0.001). These results suggest that PTA may result in marked release of prostacyclin by the damaged arterial wall, which could account for the decreased responsiveness of the artery to exogenous norepinephrine.     

3H-1,2-二氢-1-吡里酮衍生物的合成

发现3 H-1,2-二氢-1-吡咯里嗪酮具有明显的抗炎镇痛作用。用Friedel-Crafts酰化和Dieckmann缩合等反应制备了该酮的一些衍生物,其中五个未见于文献报道。药理实验证明,这些化合物均有不同程度的抗炎镇痛作用。     

Intracranial complications of ear disease in a pediatric population with special emphasis on subdural effusion and empyema

Between the years 1963 to 1982, 84 consecutive cases of intracranial complications of ear disease in pediatric patients were diagnosed and treated at the North Carolina Baptist Hospital. This group consisted of 65 patients with otitic meningitis, four with otitic brain abscess, four with otitic hydrocephalus, three with lateral sinus thrombosis, three with otitic subdural empyemas, and five with an otitic subdural effusion of fluid. The advent of antibiotics has drastically altered the natural history of middle ear infections. We present these 84 cases to review diagnostic problems and therapeutic options, and to offer a plea for continued awareness of the middle ear as a potential source of central nervous system complications.     

Percutaneous transluminal angioplasty of the femoropopliteal artery: initial and long-term results

Patients with dilated stenoses and recanalized occlusions were evaluated to assess the initial and long-term results of percutaneous transluminal angioplasty (PTA) in the femoropopliteal artery. The follow-up period was at least 1 year. The initial success rate was 84% (128/164). The initial results were influenced by the radiologist's experience, catheter selection, and type of lesion. The 5- and 7-year cumulative patency rates were 70% and 60%. There was no difference in long-term patency between initially successful stenoses and short (less than 3 cm) occlusions. Both the morphology and location of the stenotic lesion influenced the long-term results. Although many factors influence the initial and long-term success rate, results of this study justify PTA in the femoropopliteal artery. Patients with localized stenoses and short occlusions are best suited for this treatment.