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Synthesis of a calcium-binding amino acid, gamma-carboxyglutamic acid, is a vitamin K–dependent enzymatic process. Warfarin inhibits gamma-carboxyglutamic acid synthesis and, therefore, might diminish the calcification of porcine bioprosthetic valves. To evaluate this, we studied 40 porcine bioprosthetic valves removed because of spontaneous degeneration; 17 patients were treated with warfarin (prothrombin time ≥1.5 control) and 23 were untreated. Gross visualization of calcification corresponded closely to x-ray visualization of calcification in explanted valves. No grossly visible calcification or only a single localized nodule was shown in 11 of 17 valves (65%) in treated patients and in only five of 23 valves (22%) in untreated patients (p < 0.02). Histologic examination showed no calcium or only fine specks of calcium in nine of 13 valves (69%) among warfarin-treated patients and three of 19 valves (16%) from untreated patients. Warfarin, therefore, administered in usual clinical doses, appeared to diminish calcification in spontaneously degenerated porcine bioprosthetic valves.

The surface structure of leaflets from two processed but unimplanted porcine bioprosthetic valves and six degenerated porcine bioprosthetic valves that were surgically removed because of valvular dysfunction after approximately 4 to 7 years implantation were studied with the scanning electron microscope. Variable degrees of endothelial denudation with the resultant exposure of corresponding areas of subendothelial fibers was the typical surface characteristic of the processed but unimplanted porcine valve heterograft. Structural alterations demonstrated on the surface of leaflets from the degenerated porcine bioprosthetic valves included loss of endothelial cells, exposure of large areas of basement membrane material, exposure of wide expanses of subendothelial fibers, fibrin formation, the presence of activated leukocytes, adherent single platelets as well as reversible and irreversible platelet aggregates, and focal accumulations of crystalline deposits. Each of these morphologic features may be a potential contributor to the progressive degradative process.

Transmission electron microscopy with a standardized in vitro method was used to evaluate the degree of blood platelet reactivity in 72 normal subjects and 72 patients with valvular heart disease. Among the patients with abnormal natural heart valves, 51 had either aortic insufficiency or aortic stenosis, and 21 patients showed either mitral insufnciency or mitral stenosis. For normal subjects, the platelet differential counts were dominated by the dendritic type platelet, and only a few platelets showed cytoplasmic spreading between adjacent pseudopodia (spread type). A hyperactive response was defined as greater than 20% of the spread type platelet or more than 93 aggregates per 100 single platelets counted, or both. Only 6 (8%) of the 72 normal subjects showed hyperactive platelets. In contrast, 45 (62%) of the 72 patients with valvular heart disease had hyperactive platelets (p < 0.01). For patients with abnormal valves, the mean percent of the spread type platelet was 35% with a mean value of 105 platelet aggregates. The increased level of platelet reactivity was independent of both the position of the valve (aortic versus mitral) and its functional status (insufficient versus stenotic). Disturbed flow and the exposure of subendothelial throm-biis-producing materials are features associated with abnormal heart valves. These factors, which usually occur in combination, may explain the hyperactive platelet response found in these patients.

The emigration sequence and cytology of acute inflammation produced by a variety of stimulants was studied in dogs using a modified skin window procedure. Control lesions revealed the typical acute inflammatory cycle with an early influx of polymorphonuclear neutrophils and a later increase in lymphocytes, hypertrophied lymphocytes and macrophages. Either fibrinogen, fibrin or proteolytic enzymes that promote fibrin formation selectively attracted eosinophils into the inflammatory site. Neither histamine nor albumin produced significant eosinophil migration in the 10 hours under study. The fluorescent antibody technic was employed to assess the level of cellular profibrinolysin. Only inflammatory eosinophils and bone marrow eosinophils were marked with rhodamine antiprofibrinolysin. Staining was confined to intra- and extracellular eosinophil granules and coalesced masses. The intensity of fluorescence varied somewhat and perhaps reflected profibrinolysin release into the inflammatory exudate. Exudative eosinophils like all members of the bone marrow eosinophilic series contain profibrinolysin localized in the specific granules. Eosinophils which migrate and collect at an inflammatory site clearly transport profibrinolysin to an area of fibrin deposition. Granule release of profibrinolysin provides one mechanism for fibrinolysis that likely facilitates wound repair.

A previously unrecognized property of the human eosinophil is described; namely, profibrinolysin localization within the eosinophilic granules of bone marrow cells. For this demonstration the fluorescent antibody technic was employed. Highly specific fluorescent antiprofibrinolysin marked all members of the eosinophilic series. As maturation proceeded, the profibrinolysin content increased with the greatest intensity of fluorescence seen in the mature eosinophils. These findings are compatible with the view that the bone marrow eosinophil is the site of profibrinolysin synthesis. Mature eosinophils in peripheral blood smears consistently stained less intensely. Apparently profibrinolysin is tranported from the marrow and released to the circulation and tissues when needed. These findings may be interpreted as indicating a role of the eosinophil in clot lysis and in maintaining the fluidity of the blood.

Modern supportive care which prolongs life in critically injured or septic patients is often complicated by major gastric bleeding. Since 1967, over 300 patients on the emergency service at Detroit General Hospital have required transfusion for this disease. Thirty-eight of these patients in whom bleeding did not respond or only temporarily remitted with ice-saline lavage underwent surgery. Eighteen died. Sequential photographic studies of the gastric mucosa performed prior and subsequent to bleeding revealed a wide spectrum of erosions limited to the body of the stomach. Gastric hypersecretion was present in most patients. Studies of gastric mucus were done, and histologic and electron microscopic studies were performed. Vagotomy and distal gastrectomy were the most effective operations for control of hemorrhage. Nevertheless, vagotomy and pyloroplasty are advised in selected patients who meet certain, well-defined criteria.