The coagulant-active phospholipid content is a major determinant of in vivo thrombogenicity of prothrombin complex (Factor IX) concentrates in rabbits

In vitro evaluation of prothrombin complex concentrates in a thrombin generation assay, using DAPA and purified components of the prothrombinase complex, demonstrated significant levels of coagulant- active "phospholipid replacing" activity. Quantification of this activity showed a significant correlation (r = 0.8747, p less than 0.01) with thrombogenicity measured in vivo in a stasis model in rabbits. Extracted lipid material retained full phospholipid replacing activity in the vitro assay. Thin-layer chromatographic characterization confirmed the presence of phospholipids with known coagulant activity in vitro. In vivo, the extracted material was nonthrombogenic but augmented the thrombogenicity of purified factor Xa. Substitution of a synthetic coagulant-active phospholipid (phosphatidylcholine-phosphatidylserine lipid vesicles) for the extracted phospholipid produced a similar augmentation of a factor-Xa- induced thrombogenicity in vivo. It is concluded that the coagulant- active phospholipid content of prothrombin complex concentrates is a major determinant of thrombogenicity but requires the presence of activated clotting factors for its expression in vivo.     

Effects of myocardial hypoxia and ischemia on myocardial scintigraphy

The effect of regional myocardial ischemia and hypoxia on myocardial scintigraphy was studied in patients and dogs after intravenous administration of cesium-129. Seven men with angiographically proved ischemic heart disease underwent exercise testing and ¹²⁹Cs was given immediately when ischemia was manifested in the electrocardiogram. Defects were not evident in the scintigrams of any patient. Failure to visualize a defect might be related to delayed uptake of ¹²⁹Cs by the myocardium (maximal uptake in 45 minutes). The ischemic state was dissipated before the disparity in uptake between normal and ischemic myocardium could be visualized. Cesium-129 is useful for identifying acute myocardial infarcts but should not be used to visualize transient exercise-induced regional ischemia.Six dogs were given ¹²⁹Cs after induction of regional myocardial hypoxia by perfusion of the anterior descending coronary artery with venous blood. In each, scintigraphy revealed a defect that resolved after reperfusion with arterial blood. Two other dogs were given ¹²⁹Cs before perfusion with hypoxemic blood; neither dog manifested a defect. Since perfusion was maintained by a pump these results suggest that the major cause of the scintigraphically observed defect was inadequate cellular uptake of ¹²⁹Cs rather than excessive cellular loss. Since regional myocardial hypoxia produced a reversible defect, scintigraphic studies might overestimate the size of an acute myocardial infarct in man by including the ischemic zone surrounding the infarct.     

Long-term clinical results of coronary surgery. Apropos of 400 patients followed for 5 to 11 years

Between 1976 and 1982 four hundred consecutive patients underwent coronary artery bypass surgery and were operated by the same surgical team: 345 men (88.5%) and 46 women (11.5%). The average age was 56 years (7.5% were over 75 years of age); 86% of patients were infunctional classes III and IV; 46% had triple vessel disease and 9.25% had severe stenosis of the left main stem. Left ventricular ejection fractions were decreased in 26% and very poor in 4.5% of patients. The average number of bypass grafts was 1.72 per patient and the operative mortality was 3.5%. The 10 year survival rate was 81% and 75% of these patients still thought that their condition had been improved by surgery although only 30% were completely asymptomatic and had had no further coronary event. A comparison with a control population of the same age showed better survival in the surgical group in patients surviving operation. Contrary to traditional thinking, the surgical patients suffered relatively few deaths of cardiac causes but as many, if not more, of cancer. The operated patients died of approximately the same diseases as the control population of the same age but in lower proportions for each cause of death (17 cardiovascular deaths in the control population compared with 13 in the operated group; 18 versus 10 deaths of cancer, and 18 versus 8 deaths of other causes in the control and operated patients, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Natural interferon-alpha versus its combination with 6-methyl- prednisolone in the therapy of type II mixed cryoglobulinemia: a long- term, randomized, controlled study

Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgM kappa with rheumatoid factor (RF) activity. Its etiology is unknown, although recent evidence strongly suggests that hepatitis C virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic drugs have been used in the therapy of MC patients. Recently, favorable results with recombinant interferon-alpha (rIFN alpha) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-alpha (nIFN alpha), alone and in combination with 6- methyl-prednisolone (PDN), in a prospective, randomized, controlled trial in patients with symptomatic MC. Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients received nIFN alpha (3 MU) intramuscularly (IM) three times weekly, whereas 17 patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18 patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was discontinued after 1 year and patients were monitored for 8 to 17 months (mean, 13). A complete response was achieved in eight of 15 patients (53.3%) treated with nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha plus PDN, as compared with three of 18 patients (16.7%) who received PDN only (P < .05) and one of 15 (6.7%) untreated controls (P < .01). Partial response occurred in two of 15 (13.3%) patients treated with nIFN alpha, three of 17 (17.6%) who received nIFN alpha plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%) controls. A complete response in six patients (66.7%) was achieved within 3 months in the group that received nIFN alpha plus PDN, as compared with two patients (25%) of those who received nIFN alpha alone (P < .02). In anti-HCV-positive patients, the clinical response occurred in step with reduced or undetectable levels of HCV RNA and transaminase normalization. Quantification of circulating HCV RNA represented a good predictive response marker. The probability of relapse within 3 months after treatment was 100% (three of three patients) and 75% (six of eight patients), respectively, in patients who received PDN alone or nIFN alpha alone as compared with none of those who received nIFN alpha plus PDN (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Wegener's Granuloma. A Series of 265 British Cases Seen Between 1975 and 1985. A Report by a Sub-committee of the British Thoracic Society Research Committee

In order to describe the British experience of Wegener's granuiomatosisHospital Activity Analysis was used to collect cases diagnosedin England, Wales and Scotland between 1975 and 1985. Wherepossible clinical details, histological material and chest radiographswere obtained. Two hundred and sixty five patients were consideredto have Wegener's granuiomatosis. In 109 a single pathologistconfirmed the diagnosis by finding both granulomas and vasculitisin biopsy material. The diagnosis was made on clinical groundsor clinical grounds together with histological diagnosis inthe local hospital in 156 patients. Wegener's granuiomatosiswas confined to the lung or upper respiratory tract in 22 percent of patients and renal disease occurred in 58 per cent.Laboratory tests showed a pattern of mild anaemia, polymorphleucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia,with no specific pattern of changes. Histological confirmation was most frequently obtained by examinationof nasal biopsy specimens, but multiple biopsies were oftenrequired. Renal biopsies showed focal proliferative glomerulonephritisbut granulomatous glomerulonephritis was uncommon. Of availablechest radiographs 61 per cent were abnormal, large opacitiesbeing most common. Small irregular opacities were found lessoften and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients receivedno drug therapy. This large series illustrates that even withoutspecific treatment, patients with Wegener's granuiomatosis cansurvive for several years and with modern treatment survivalfor more than a decade is possible. Conclusions about the effectivenessof the various therapies cannot be drawn from this restrospectivestudy. Renal failure and disseminated vasculities were the commonestcauses of death; death was considered to result from complicationsof treatment with cytotoxic drugs or prednisolone in 6 per centof patients.     

Randomized Blinded Study Comparing a Bipolar Sealer and Standard Electrocautery in Reducing Transfusion Requirements in Anterior Supine Intermuscular Total Hip Arthroplasty

Managing blood loss in total hip arthroplasty (THA) minimizes complications and decreases cost. Tissue-sparing anterior supine intermuscular THA (ASI-THA) may offer a quicker recovery but increases blood loss and transfusion requirements. This double-blinded prospective study compared a bipolar sealer (Aquamantys 6.0 bipolar sealer) to standard monopolar electrocautery in reducing blood loss in ASI-THA. Differences in calculated actual blood loss (ABL), hemoglobin, and transfusion requirements were examined. One hundred hips were randomized to each group. Transfusion rates were similar, 6% and 4%, respectively (p > 0.05). ABL and change in hemoglobin were identical (1.35 and 3.3 g). No significant differences in transfusion, blood loss, or hemoglobin were seen with a bipolar sealer device. Routine use of this bipolar sealer device has been discontinued in ASI-THA.     

Time course of the interaction between tadalafil and nitrates

OBJECTIVES: This study was designed to determine the time course of nitrate interaction with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor with a half-life (t(1/2)) of 17.5 h. BACKGROUND: The PDE5 inhibitors augment the blood pressure (BP)-lowering effects of nitrates, yet the time course of this interaction is unclear. Recent guidelines from the American College of Cardiology/American Heart Association recommend that nitrates be withheld for 24 h after taking sildenafil (t(1/2) = 4 h). METHODS: Male subjects (n = 150) received seven consecutive daily doses of placebo or tadalafil (20 mg). On day 7 and beyond, subjects received repeated doses of sublingual nitroglycerin (0.4 mg) after the last dose of placebo or tadalafil. After a 10- to 21-day washout period, subjects crossed over to either placebo or tadalafil, and nitrate dosing was repeated. RESULTS: In response to nitroglycerin at 4, 8, and 24 h, standing systolic BP fell below 85 mm Hg in more subjects on tadalafil compared with placebo (p < 0.05), with no difference in the response to nitroglycerin at 48, 72, and 96 h (p > 0.2). Similar observations were made for standing diastolic BP <45 mm Hg, decrease in systolic BP >30 mm Hg, and decrease in diastolic BP >20 mm Hg. Nitroglycerin also evoked greater mean maximal decreases in standing systolic BP at 8 and 24 h after taking tadalafil versus placebo (p < 0.02), with no significant difference at 48, 72, or 96 h (p > 0.49). CONCLUSIONS: The hemodynamic interaction between tadalafil and sublingual nitroglycerin lasted 24 h, but was not seen at 48 h and beyond. Similar to other PDE5 inhibitors, tadalafil should not be administered in combination with organic nitrates.