Immunotherapy of coccidioidomycosis.

Transfer factor (TF) derived from donors with strong delayed hypersensitivity to coccidioidin (CDN) was administered to four patients with active disseminated or progressive pulmonary coccidioidomycosis. The clinical and immunologic response to TF was studied. Before the administration of TF, all four patients had defective thymus-derived lymphocyte (T-cell) function. In no case were lymphocytes in culture stimulated to incorporate [(3)H]thymidine when exposed to CDN. Cases 1 and 2 had no skin test response to CDN or other antigen, nor was antigen-induced migration inhibition factor (MIF) release detected. Cases 3 and 4 had skin reactivity to CDN as well as MIF release. Lymphocyte reactivity to phytohemagglutinin (PHA), as measured by the incorporation of [(3)H]thymidine, was low or absent in all. After the administration of TF, patients with negative skin tests became reactive to CDN, MIF release was present in all but case 1, and lymphocyte stimulation was present in response to CDN in all. Lymphocyte reactivity to PHA was also increased after the administration of TF in all cases. All responses to single doses of TF were transient, lasting no more than 10 days. Subsequent doses were less effective at restoring lymphocyte stimulation once it had waned. Multiple doses of TF administered at frequent intervals appear to be the most effective way to maintain lymphocyte reactivity. Clinical response to the administration of TF correlated closely with specific transfer as measured by response to CDN in skin test, lymphocyte stimulation, and MIF release. After TF administration, all patients mounted a more effective host response against the infecting fungus. In each patient, smears and cultures became negative. Fistulas, when present, diminished in extent or closed; and pulmonary infiltrates cleared. Nonspecific signs of infection such as fever, weight loss, and anorexia also improved. Clinical improvement paralleled immunologic improvement. When immunologic improvement was transient so was clinical improvement. Multiple doses of TF at frequent intervals may maintain transferred T-cell reactivity. TF may prove to be a useful adjunct in the management of patients with coccidioidomycosis. Whether TF from CDN-negative donors may have similar effects is not known and requires exploration.

Lamellar body depletion in dogs undergoing pulmonary artery occlusion.

We have investigated the relationship between pulmonary artery occlusion (PAO) and the surfactant system of the lung by studying the ultrastructural responses of type II alveolar pneumocytes to PAO of 4-12 h duration in 16 mongrel dogs. In six of these animals, the occluded lung was allowed to reperfuse for 6 h before killing and in four animals subjected to PAO of 4 h duration, the occluded lung was ventilated with 5% CO2 balance air. PAO by itself resulted in a dramatic 80% reduction in the volumetric density of lamellar bodies (LB) in the type II cells. This resulted predominantly from a decrese in volume of the individual LB. Although reperfusion was associated with an increase in LB volume density toward normal, 6 h of reperfusion was insufficient to re-establish normal type II cellular morphology. Ventilation of the occluded lung with 5% CO2 prevented LB depletion indicating that alveolar CO2 tension may affect the release and/or synthesis of LB in type II pneumocytes.

Evidence of lung surfactant abnormality in respiratory failure. Study of bronchoalveolar lavage phospholipids, surface activity, phospholipase activity, and plasma myoinositol.

Autopsy findings suggest that lung surfactant is damaged in the adult respiratory distress syndrome. In the present study 225 bronchoalveolar lavage specimens (78 from 36 patients, 1-78 yr old with respiratory failure, 135 from another 128 patients with other respiratory disease, and 12 from healthy controls) were assayed for the lung profile [lecithin/sphingomyelin (L/S) ratio, saturated lecithin, phosphatidylinositol, and phosphatidylglycerol]. Bronchoalveolar lavage fluid was further analyzed for phospholipids and for phosphatidic acid phosphohydrolase, phospholipase A2, and phosphatidylinositol phosphodiesterase activities. A lipid-protein complex was isolated and analyzed for surface activity, and plasma was measured for myoinositol. There were only small differences seen in the recovery of total phospholipid between respiratory failure patients and normal controls. However, in respiratory failure, phospholipids in bronchoalveolar lavage were qualitatively different from those recovered either from normal controls or from patients with other lung disease: the LO/S ratio, phosphatidylglycerol, and disaturated lecithin were low, whereas sphingomyelin and phosphatidylserine were prominent. These abnormalities were present early in respiratory failure and tended to normalize during recovery. Low L/S ratio (less than 2), and low phosphatidylglycerol (1% or less of glycerophospholipids) in bronchoalveolar lavage was always associated with respiratory failure. Abnormal lavage phospholipids were not due to plasma contamination. The phospholipase studies revealed little evidence of increased catabolism of phospholipids. In respiratory failure, the lipid-protein complexes from lung lavage were not surface active, whereas that from healthy controls had surface properties similar to lung surfactant. Phospholipids from patients with respiratory failure were similar to those from respiratory distress syndrome in the newborn. However, the latter condition is characterized by fast recovery of surfactant deficiency and by high plasma myoinositol that suppresses the synthesis of surfactant phosphatidylglycerol and increases phosphatidylinositol (Pediatr. Res. 1981. 15: 720). On the other hand, in adult respiratory distress syndrome, the abnormality in surfactant phospholipids may last for weeks and in most cases is associated with low phosphatidylinositol, low phosphatidylglycerol, and low plasma myoinositol.

Changes in procoagulant and fibrinolytic gene expression during bleomycin-induced lung injury in the mouse.

Bleomycin-induced lung injury is an established murine model of human pulmonary fibrosis. Although procoagulant molecules (e.g., tissue factor [TF]) and fibrinolytic components (e.g., urokinase [u-PA] and type 1 plasminogen activator inhibitor [PAI-1]) have been detected in alveolar fluid from injured lungs, the origin of these molecules remains unknown. We therefore examined the expression of procoagulant and fibrinolytic components in relation to the distribution of parenchymal fibrin in bleomycin-injured lungs. Extravascular fibrin localized to the alveolar and extracellular matrix in injured lung tissue. Injured lung tissue extracts contained elevated levels of PAI-1 activity and decreased levels of u-PA activity. Whole lung PAI-1 and TF mRNAs were dramatically induced by lung injury. In situ hybridization of injured lungs revealed that PAI-1, u-PA, and TF mRNAs were induced within the fibrin-rich fibroproliferative lesions, primarily in fibroblast-like and macrophagelike cells, respectively, while TF mRNA was also induced in perilesional alveolar cells. Taken together, these observations suggest that the induction of PAI-1 and TF gene expression plays and important role in the formation and persistence of extracellular fibrin in bleomycin injured murine lungs.

Early changes of right heart geometry after pulmonary thromboendarterectomy.

To determine the changes in right heart hemodynamics and geometry early after surgery for chronic pulmonary hypertension due to large vessel thromboembolic occlusion, 30 patients were evaluated 8 +/- 8 days (mean +/- SD) before and 6 +/- 4 days after pulmonary thromboendarterectomy by two-dimensional echocardiography and right heart catheterization. Surgery resulted in an early significant improvement in hemodynamic variables including mean pulmonary artery pressure (48 +/- 12 to 28 +/- 8 mm Hg, p less than 0.001), right ventricular systolic pressure (76 +/- 20 to 47 +/- 15 mm Hg, p less than 0.001), pulmonary vascular resistance (935 +/- 620 to 278 +/- 252 dynes.s.cm-5, p less than 0.001) and cardiac index (2.0 +/- 0.5 to 2.9 +/- 0.6 liters/min per m2, p less than 0.001). Similarly, echocardiographic variables of right heart structures, which were well outside the normal range preoperatively, improved significantly early after thromboendarterectomy. These included diameters of the pulmonary artery (2.8 +/- 0.3 to 2.4 +/- 0.4 cm, p less than 0.001), inferior vena cava (2.9 +/- 0.6 to 2.2 +/- 0.4 cm, p less than 0.001) and right atrium (6.8 +/- 1.5 to 5.9 +/- 1.5 cm, p less than 0.001) as well as right ventricular short axis (4.5 +/- 0.8 to 3.7 +/- 0.8 cm, p less than 0.001) and long axis (8.7 +/- 0.9 to 8.1 +/- 0.9 cm, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Transvenous procurement of pulmonary artery smooth muscle and endothelial cells using a novel endoarterial biopsy catheter in a canine model.

OBJECTIVES: The aim of this study was to evaluate the performance of a new arterial biopsy catheter in obtaining pulmonary endovascular samples in a canine model. BACKGROUND: Percutaneous endomyocardial biopsy is a widely used and valuable procedure in the management of posttransplant rejection and selected cardiomyopathies. A similar method of obtaining endoarterial biopsy samples would aid in the study, diagnosis and management of arterial diseases. METHODS: Catheterization was performed in 19 dogs, each weighing 20 to 30 kg, through an 8F sheath in the external jugular vein to obtain pulmonary endoarterial samples. The catheter consists of two sliding tubes: an inner one with a beveled opening that accommodates endoarterial tissue by means of a vacuum and an outer tube with a sharp distal edge that cuts the tissue when activated. RESULTS: Overall, a total of 266 separate biopsy attempts were performed, and 161 tissue samples were obtained (success rate 61%). With modifications in technique in the last nine dogs, 54 (93%) of 58 attempts were successful. There were no deaths, extravasation of contrast material on angiography or thrombi. Of 20 vessels with prebiopsy and postbiopsy angiograms, 1 developed transient spasm (5%). On microscopic examination of cross sections of 50 separate pulmonary endoarterial biopsy samples, all had smooth muscle cells and 30 contained endothelial cells (60%). The arteries of origin showed small intimal and medial tears and mild perivascular hemorrhage. Angiographic and pathologic examination of previously biopsied arterial segments 2 weeks (two dogs) and 8 weeks (two dogs) after the procedure showed patent vessels and no thrombi. Histologically, the biopsy sites revealed mild neointimal and medial proliferation. CONCLUSIONS: This new endoarterial biopsy catheter is safe and effective in obtaining pulmonary artery samples in normotensive dogs.

Harvesting the noncirculating pool of polymorphonuclear leukocytes in rats by hetastarch exchange transfusion (HET): yield and functional assessment.

Isolation of polymorphonuclear leukocytes (PMN) provides an opportunity to study PMN activity in vitro and to label PMN for study of in vivo kinetics. However, simple phlebotomy (SP) of a small animal frequently yields too few PMN for in vitro handling, while PMN harvested from an induced-peritonitis may not accurately reflect PMN in a less stimulated state. We report a novel method of harvesting PMN from the circulation of rats, using hetastarch exchange transfusion (HET), which is both time and animal sparing. HET harvested 8-fold more PMN than SP. In vitro cell function was examined with assays of adherence, chemotaxis, bacterial killing, and superoxide generation. No significant (p less than 0.05) difference was found between PMN obtained by HET and pooled-PMN obtained by SP. In vivo function was examined following labeling with indium111-oxine. The kinetics pattern described suggested normal migratory activity when compared to previous reports. The data demonstrate that rats possess a relatively large, noncirculating pool of PMN which is readily accessible by HET.

Transfer factor therapy for histoplasmosis in a patient with Hodgkin's disease.

A patient with recurrent chronic histoplasmosis was diagnosed also as having Hodgkin's disease. Studies of cell-mediated immunity (CMI) demonstrated no reaction to histoplasmin by skin test, lymphocyte transformation (LT), or leukocyte inhibition factor (LIF) assay. Clinical and immunologic studies were performed during treatment with 19 doses of dialyzable transfer factor (TF) prepared from a normal donor with strong CMI against histoplasmin. Transfer of CMI to the patient was demonstrated by all three tests. All tests reverted to nonreactive during the period of observation. Repeated doses of dialyzable TF were followed by reconversion of skin tests. The LIF assay was most reactive. Reactivation of histoplasmosis occurred during antimetabolic therapy for Hodgkin's disease; however, the lesions cleared rapidly when TF was added to amphotericin B. Amphotericin B was administered at a dosage of 25 mg three times each week during the entire study.

Results of a comprehensive rehabilitation program. Physiologic and functional effects on patients with chronic obstructive pulmonary disease.

Forty-two patients with chronic obstructive pulmonary disease participated in a comprehensive inpatient rehabilitation program. Criteria for a safe, maximum treadmill exercise regimen were established; all patients pursued this regimen for six weeks, without complications, even though 31 of 39 patients showed a decline in PaO2 with exercise. Postprogram O2 consumption, minute ventilation, heart rate, and respiratory rate were significantly reduced during exercise when compared with preprogram values. Sixteen of 29 patients improved in terms of dyspnea class; an additional 11 of these 29 improved with regard to activities of daily living. Most patients who improved physiologically also improved functionally. Patients able to tolerate higher levels of treadmill exercise initially had the greatest improvement in postcourse exercise performance. The data suggest that precourse functional and exercise classification is useful in selecting candidates who will receive the greatest functional benefits from participation in rehabilitative programs.

Lupus anticoagulant, heparin use, and thrombocytopenia in patients with chronic thromboembolic pulmonary hypertension: a preliminary report.

PURPOSE: An increased occurrence of thrombotic events has been described in patients exhibiting a lupus anticoagulant (LA). In patients with chronic, major vessel thromboembolic pulmonary hypertension, not only has there been a relatively high frequency of the LA, but also an unexpected association with heparin-related thrombocytopenia. This retrospective report emphasizes the frequency of this association. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 216 patients admitted to the University of California, San Diego, Medical Center who were being considered for surgical correction of their chronic thromboembolic pulmonary hypertension. For each patient, the following information was sought: presence of an LA, variation in platelet numbers during the preoperative evaluation, and determination of whether an observed thrombocytopenia was related to heparin use. RESULTS: An LA was found in 23 of the 216 patients (10.6%). Of the remaining patients, sufficient platelet data for comparison were available for 68 patients. These 68 patients constituted the control group. Within the LA group, platelet counts during the preoperative evaluation declined to 51.6% +/- 16.7% of baseline counts, a highly significant difference (P < 0.0001) compared with the non-LA control group, who underwent a comparable evaluation with similar heparin exposure. In addition, heparin-associated thrombocytopenia developed in 13 of the 23 LA patients (56.5%) and in none of the control patients. Heparin-induced arterial thrombosis was implicated as the cause of a myocardial infarction in 1 of the patients with heparin-associated thrombocytopenia. CONCLUSIONS: In patients with chronic thromboembolic pulmonary hypertension, a high incidence of the LA and an accompanying association with heparin-related thrombocytopenia have been observed. Although further prospective studies of this relationship are needed, physicians should be alert to the possibility of thrombocytopenia when using heparin for patients exhibiting an LA.

Intravenous administration of alpha-1-proteinase inhibitor in patients of PiZ and PiM phenotype. Preliminary report.

Nine patients with moderate pulmonary emphysema, six of PiZ phenotype and three of PiM phenotype, have received a single intravenous infusion of alpha-1-proteinase inhibitor (human) (A1PI), in a dose of 60 mg/kg over a 30-minute period. They also received a tracer dose (300 microCi) of 131I-labeled A1PI. No active or passive immunization against hepatitis was given. No acute toxicity was observed. Compared with baseline data, significant elevations of serum A1PI (measured both antigenically and as anti-elastase activity) occurred, with a serum half-life approximating 110 hours. Bronchoalveolar lavage fluid, obtained 48 hours after infusion, reflected a significant increase in A1PI concentration versus baseline bronchoalveolar lavage fluid values. Serial gamma camera images of the lungs confirmed persistence of enhanced lung radioactivity for several days. Urinary desmosine excretion did not change following A1PI infusion. During the period of follow-up thus far, no patient has had chronic toxicity, results of liver function tests have been stable, and there has been no development of hepatitis B antigen or antibodies to hepatitis B surface or core antigens.

Right and left ventricular dysfunction in patients with chronic obstructive lung disease. Assessment by first-pass radionuclide angiography.

To evaluate the relationship between right and left ventricular function in patients with obstructive lund disease, we studied 10 normal subjects (group 1) and 37 patients with chronic obstructive pulmonary disease by first pass radionuclide angiography. These 37 patients were divided into three groups: nine with mild chronic obstructive pulmonary disease (group 2), 20 with severe chronic obstructive pulmonary disease (group 3) and eight with severe chronic obstructive pulmonary disease and primary left ventricular disease (group 4). In each subject right ventricular ejection fraction (RVEF), left ventricular ejection fraction (LVEF) and ejection fraction during first third of systole (first third LVEF) were calculated. (For table: see text.) p less than 0.05 versus 1. All subjects in group 2 had normal left ventricular and right ventricular function. In group 3, 11 of 10 (55 per cent) had a low RVEF and three of 20 (15 per cent) a low LVEF. However eight of 20 in this group (40 per cent) had a depressed first-third LVEF. The correlation between decline in RVEF and first-third LVEF was good r = 0.73. We conclude that (1) certain indices of early systolic left ventricular ejection are abnormal in many patients with chronic obstructive pulmonary disease and correlate with the decline in right ventricular function; (2) this is not seen in patients with mild chronic obstructive pulmonary disease and is worse in patients with underlying left-sided heart disease.

Effects of isoproterenol on distribution of perfusion in embolized dog lungs.

In 19 mechanically venilated, anesthetized dogs, autologous venous thrombi were formed in the inferior vena cava and subsequently released. Serial perfusion lung scintigrams revealed the postembolic distribution of pulmonary blood flow before, during, and after the infusion of isoproterenol at 2.2 micrograms/min. Isoproterenol failed to restore perfusion to embolically occluded regions. When reperfusion occurred it was attributable to clot resolution. Gas exchange and hemodynamic measurements obtained in seven thromboembolized animals showed no scan evidence of reperfusion during the isoproterenol infusion. After embolization, cardiac output increased from 1.7 to 2.6 liter/min (p less than 0.05), and PvO2 from 38.0 to 45.3 mm Hg (p less than 0.05). Shunt fraction remained unchanged. The postembolic infusion of isoproterenol was associated with a further increase in cardiac output to 3.6 liter/min (p less than 0.01), an elevation in PvO2 to 50.7 mm Hg, along with a decrease in pulmonary vascular resistance from the postembolic mean of 448 to 246 dynes.sec.cm-5 (p less than 0.05). Perfusion defects following acute pulmonary thromboembolization are not altered by the infusion of the potent pulmonary vasodilator, isoproterenol. Infusion of this drug following thromboembolization may have potential therapeutic benefit by reducing pulmonary vascular resistance, increasing cardiac output, and elevating the mixed-venous oxygen tension.

Is lung sequestration of indium-111-labeled granulocytes organ specific?

Transient sequestration of polymorphonuclear leukocytes (PMN) in the normal lungs of animals occurred immediately following intravenous injection of 111In-labeled PMN. We investigated the organ specificity of this process. Equal amounts of homologous PMN, derived from the intravascular space and labeled with [111In]oxine, were infused either intravenously (i.v.) or intraarterially (i.a.) into pairs of rats. Changes in radioactivity emitted from three regions--representing lung, liver and spleen, and lower body--were determined from images during the following hour. A nonspecific character was demonstrated by the transient sequestration of activity in the lower body following i.a. infusions. However, the rate of initial clearance of activity (first 30 min) from the lungs of i.v.-infused rats was relatively slower than from the lower body of i.a.-infused rats. This suggests the presence of a lung-specific as well, which may be important for localization of PMN-related events to the lung.

Study of factors that may condition scintigraphic detection of venous thrombi and pulmonary emboli with indium-111-labeled platelets.

Incorporation of indium-111-labeled platelets (In-111-P) into venous thrombi and pulmonary emboli may permit rapid detection of these thromboemboli by gamma imaging. In a series of dogs in which femoral-vein thromboses and/or pulmonary embolism were induced experimentally by stasis and small amounts of thrombin, we addressed several questions pertinent to the sensitivity, specificity, and potential applicability of this approach. We found that when In-111-P were injected intravenously before thrombus induction or embolus release, femoral-thrombus images were consistently detectable within 15 min, whereas control femoral-vein images were unremarkable. Pulmonary emboli were also promptly imaged, and such In-111-P images agreed well with defects on Tc-99m MAA perfusion scans. When thrombi were aged in vivo for up to 10 hr after formation, they could still be imaged within 20-90 min after In-111-P injection. Administration of heparin, as an initial bolus followed by constant infusion, blocked platelet deposition on femoral-vein thrombi as assessed by both thrombus-to-blood ratios and failure to image. Injection of protamine at 6 hr, however, resulted in prompt thrombus imaging. These data indicate that this approach may well have applicability to the detection of thromboemboli in humans, since imaging remains possible in canine thrombi aged in vivo for 10 hr so long as heparin therapy has not been instituted. The dose of heparin required to inhibit imaging is not known. However, if these data prove comparable in humans, they suggest that imaging of thromboemboli could be achieved so promptly that only modest delay in the institution of heparin therapy would be required.

Degree of polymer organization decreases the binding of a monoclonal antibody raised against the beta-chain amino terminus of fibrin.

UNLABELLED: Accurate non-invasive diagnosis of deep venous thrombosis and pulmonary embolism remains an elusive goal. Radiolabeled antibodies specific for the epitope exposed on the beta-chain of fibrin after fibrino-peptide B release (anti-beta) enabled in situ imaging of thrombi in experimental subjects with nuclear medicine techniques. When used in patients anticoagulated for thrombo-embolic disease, however, the antibody was unable to reliably image the thrombi. We postulated that the neoepitope on the beta-chain of fibrin is covered up as fibrin organizes into a polymer network and is therefore exposed to the antibody only during active incorporation of fibrin subunits. We determined the equilibrium binding kinetics of an anti-beta monoclonal antibody to fibrin in various stages of organization. The concentration of exposed epitopes on immobilized fibrin monomers was equal to the molar concentration of fibrin beta-chains. The percentage of beta-chains exposed to the antibodies markedly decreased as the fibrin network was allowed to organize, a process catalyzed by calcium. CONCLUSIONS: The beta-chain amino terminus of fibrin is exposed transiently as subunits are added to the enlarging fibrin network. Anti-beta antibodies bind preferentially to actively enlarging fibrin polymers.

Catheter-based intravascular ultrasound imaging of chronic thromboembolic pulmonary disease.

Pulmonary thromboendarterectomy is now the treatment of choice for pulmonary hypertension due to chronic pulmonary thromboemboli. A precise assessment of location and extension of these thrombi is important because only proximal chronic pulmonary thromboemboli are accessible to surgery. Because intravascular ultrasound imaging can assess not only arterial luminal size, but also wall thickness, its value as a complement to angiography was assessed in 11 patients aged 35 to 64 years with severe pulmonary hypertension (systolic pulmonary artery pressure, mean +/- standard deviation 70 +/- 19 mm Hg; pulmonary artery resistance, 609 +/- 297 dynes.s.cm-5). Intravascular ultrasound was obtained in 10 of 11 patients and no complication occurred. Intravascular ultrasound identified 10 segments with suspected chronic pulmonary thromboemboli in 7 patients, all confirmed at operation. Nine segments were considered normal, all of which (except 1) were free of chronic pulmonary thromboemboli at operation. Image quality was highly dependent on pulmonary artery size and position of the catheter. Therefore, intravascular ultrasound of pulmonary arteries is feasible and safe in patients with pulmonary hypertension. It may help to assess the location and extension of the pathologic process involving pulmonary arteries.

Doppler assessment of changes in right-sided cardiac hemodynamics after pulmonary thromboendarterectomy.

It is not known whether Doppler echocardiography can accurately follow changes in right-sided cardiac hemodynamics after a therapeutic intervention in patients with pulmonary artery (PA) hypertension. Therefore, Doppler measurements of the maximal velocity of the tricuspid regurgitant jet and the acceleration time of the PA velocity profile were obtained in 28 patients before and after pulmonary thromboendarterectomy for chronic thromboembolic PA hypertension. Doppler values were compared with hemodynamic variables obtained at cardiac catheterization. Postoperatively, decreases in mean PA pressure (50 +/- 14 to 28 +/- 8 mm Hg), transtricuspid systolic pressure difference (69 +/- 21 to 36 +/- 14 mm Hg) and Doppler measurement of the maximal velocity of the tricuspid regurgitant jet (4.1 +/- 0.7 to 2.7 +/- 0.5 m/s) were noted, while acceleration time increased (57 +/- 16 to 94 +/- 18 ms, all p less than 0.001) compared with preoperative values. For the population as a whole, the calculated systolic transtricuspid pressure difference determined from the maximal velocity of tricuspid regurgitation correlated well with the catheterization systolic transtricuspid pressure difference (r = 0.93, p less than 0.001) and the acceleration time correlated with mean PA pressure (r = -0.81, p less than 0.001). More importantly, the change in the maximal velocity of tricuspid regurgitation for postoperative patients was found to correlate with the change in catheterization systolic transtricuspid pressure difference (r = 0.82, p less than 0.001), while the change in acceleration time correlated weakly with the change in mean PA pressure (r = -0.41, p = 0.053).(ABSTRACT TRUNCATED AT 250 WORDS)

Right ventricular pathology in chronic pulmonary hypertension.

Right ventricular free wall biopsy specimens in 40 patients undergoing surgery for relief of chronic thromboembolic pulmonary hypertension were normal in 5%, disclosed only myocyte hypertrophy in 80%, mild focal fibrosis in 12.5%, and myocarditis in 2.5%. There was no relation between postsurgical functional or hemodynamic outcomes and the presence of focal fibrosis.

Imaging of venous thromboemboli with labeled platelets.

Prevention and optimal treatment of venous thromboembolism requires techniques that can: (1) monitor patients at high risk; (2) promptly detect thromboemboli; (3) follow the course of patients during treatment. Multiple techniques have been introduced to assist in these tasks. Some have not been well validated. Others, while established as of substantial value, have limitations with respect to specificity, sensitivity, patient access, patient acceptability, or risk. The dynamic nature of venous thromboembolism makes it unlikely that any one procedure will satisfy all diagnostic needs. Platelets labeled with 111In (111In-P) have promise as a useful addition to the existing diagnostic armamentarium. Because 111In-P are incorporated into forming and growing thromboemboli, and can provide a gamma camera image, they offer certain potential advantages versus other techniques. However, to establish the clinical value and proper use of the 111In-P technique, additional investigations are needed to determine the impact of thrombus location, age, anticoagulant therapy, and imaging technique and timing upon in vivo visualization of thromboemboli.