Ultrasonographic evaluation of invasive lobular carcinoma.

PURPOSE: To compare ultrasonographic (US) and mammographic findings and tumor size measurements of invasive lobular carcinoma (ILC). MATERIAL AND METHODS: US diagnoses and mammographic findings were compared in 95 patients with pure ILC, including 46 palpable and 49 nonpalpable tumors. The diameters of tumors measured by mammography, US, and pathology were compared in 70 of the 95 patients using scatter plots and correlation analysis. RESULTS: Eighty-two (86.3%) of the ILCs were correctly diagnosed as malignant tumor, 5 (5.3%) were diagnosed as focal abnormality, and only 2 patients had normal findings on US. The most common mammographic findings were a spiculated mass (57%) and a focal asymmetric density (15%). US correctly diagnosed 8 of 12 patients with normal or equivocal mammographic findings. The correlation of tumor size assessment on imaging and pathology revealed that US measurements including the "halo" (r=0.69) was superior to that of mammography (r=0.59). ILCs larger than 30 mm were heavily underestimated by both methods. CONCLUSION: Malignant tumor was diagnosed on US in most of the patients with ILC. US tumor measurement including the "halo" predicted tumor size most accurately. The correlation between imaging measurements and tumor diameter on histology was lower for ILCs than reported for populations of mixed carcinomas.

Follow-up of localized prostate cancer, with emphasis on previous undiagnosed incidental cancer.

OBJECTIVE: To determine the natural course of incidental untreated transition zone prostate cancer and thus help to identify criteria to predict the prognosis and to determine treatment for individual patients. MATERIALS AND METHODS: A total of 1135 unselected surgical specimens of the prostate, examined during 1974 and 1975, were reviewed while unaware of case by two experienced pathologists. The patients from which the samples were obtained were followed for up to 20 years or death by The Cancer Registry of Norway and the outcome compared with the histological review. RESULTS: The histology review revealed a total of 311 cancers, of which 73 had not been initially recorded; these patients had received no treatment. The kappa coefficient for interobserver reproducibility was 0.86 for carcinoma. The follow-up showed that patient age was the strongest predictor of survival, followed by histological grade and percentage of tumour involvement. Only two of the 73 patients with untreated transition zone cancer died from prostate cancer during the follow-up, compared with 78 of 144 patients with standard management of transition zone tumours. The 5- and 10-year relative survival rates for the 144 patients with standard management of transitional zone tumours and for the 53 patients with peripheral zone tumours were 56% and 26%, and 45% and 33%, respectively. Metastasis (+ or -) was the only individual prognostic factor in the multivariate analysis. CONCLUSION: This study shows that patients with incidental low-grade tumours have a low probability of dying from prostate cancer and may thus be followed expectantly. The biological distinction between atypical hyperplasia and stage T1a cancer is unclear. The survival of men with prostate cancer is significantly reduced with loss of differentiation and with increasing tumour volvement.

[Undiagnosed microinvasive carcinomas of the prostate]. / Ikke-diagnostiserte mikroinvasive karsinomer i prostata.

Quality assurance is becoming increasingly important in all aspects of health care, but a growing workload in recent years may delay the introduction of new quality assurance procedures. In 1994-95, in order to evaluate the standard of quality in executing routine histopathological procedures, a total of 1,135 prostatic specimens representing all surgical material taken from the prostate during 1974-75 were reviewed. The patients were followed up for to 20 years by comparing with the files of The Norwegian Cancer Registry. Only a few registration errors were found. Microscopic examination in 1994-95 revealed 311 carcinomas, 83 of which were not recorded in 1974-75. 73 of the patients had not received treatment. The histology reports revealed suspected malignancy, with irregular or atypical epithelium, or both, in 42% of the 83 carcinomas not reported in 1994-95, whereas for 45 carcinomas the histology reports did not describe changes suggestive of malignancy. Only 3% of the patients not treated died of prostate cancer during the follow-up time, compared with 78 (54%) cancer deaths in the group that had received treatment. Most undiagnosed cancers were well differentiated and in the pT1a category. It is important that the clinician is aware of the fairly benign outcome of these borderline tumors in order to avoid overtreatment.

Is prostatic intraepithelial neoplasia in the transition/central zone a true precursor of cancer? A long-term retrospective study in Norway.

Prostatic intraepithelial neoplasia (PIN) has been considered as a precursor of prostatic cancer. Few reports have dealt with the long-term follow-up of PIN lesions, and there is still a lack of proof that PIN is a true premalignant lesion. The objective of this study was to evaluate PIN in the transition/central zone as a marker for subsequent development of prostatic cancer. The PIN status of tissue specimens from 789 men without prostate cancer was determined in 508 transurethral resections and 281 transvesical prostatic enucleations. All slides were reviewed blind and independently by two pathologists. The patients were followed for an average of 11 years, and the incidence of subsequent cancer and cause-specific survival were analysed. Thirty-six cases of clinical prostatic cancer occurred among the cohort of 789 men through follow-up. No association between the presence of PIN in the transition/central zone and subsequent cancer development was found. There was also no difference in survival related to PIN status among the subsequent cancer patients.

Prognostic factors in patients with metastatic (stage D2) prostate cancer: experience from the Scandinavian Prostatic Cancer Group Study-2.

PURPOSE: Nuclear texture reflects the overall structures of the chromatin organization. We recently reported the principles and prognostic importance of image analysis of nuclei from metastatic prostate cancer. Immunohistochemical up regulation of the adhesion molecule sialyl Lewis(x) is also reported to be a prognostic parameter. Presently we analyzed statistically the prognostic impact of these 2 new parameters compared to well-known clinical parameters in metastatic prostate cancer. MATERIALS AND METHODS: Prognostic factors, such as sedimentation rate, alkaline and acid phosphatases, hemoglobin, testosterone, performance status, pain due to metastasis, T category, histological grade and patient age, were included in a multivariate Cox proportional hazards regression analysis based on 262 patients from the Scandinavian Prostatic Cancer Group Study-2. Extent of bone lesions, deoxyribonucleic acid ploidy, texture analysis and sialyl Lewis(x) molecules based on subsets of these 262 patients were also analyzed in the same multivariate model. RESULTS: This test identified chromatin texture as the most important factor (p < 0.001), followed by reaction of the oligosaccharide sialyl Lewis(x) (p < 0.01). Among the routine clinical and laboratory data, sedimentation rate, alkaline phosphatase and hemoglobin (p < 0.05) showed prognostic importance. Performance status, pain due to metastasis and extent of bone lesions showed prognostic value in the univariate analysis (p < 0.05). CONCLUSIONS: These data indicate that computerized nuclear texture analysis as well as up regulation of sialyl Lewis(x) molecules may be new important prognostic factors in metastatic prostate cancer. Furthermore the prognostic importance of sedimentation rate, alkaline phosphatase and hemoglobin was confirmed.

Prostatic intraepithelial neoplasia in surgical resections: relationship to coexistent adenocarcinoma and atypical adenomatous hyperplasia of the prostate.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is associated with coincident prostate carcinoma, and has been considered to be a precursor of prostate carcinoma. Most studies on PIN have been performed on total prostatectomy or core needle biopsy specimens. Few reports deal with the occurrence of PIN in consecutive surgical resections, which is the objective of the current study. METHODS: A total of 1135 nonselected surgical specimens from the prostate, examined during 1974 and 1975, underwent blind review by 2 experienced pathologists. There were 79 core needle biopsies, 731 transurethral resections of the prostate and 325 transvesical prostatic enucleations. The kappa coefficient for interobserver reproducibility was 0.66 for PIN and 0.86 for carcinoma. RESULTS: Grade 1 PIN was found in 9%, Grade 2 PIN in 32%, and Grade 3 PIN in 20% of the total cases. Atypical adenomatous hyperplasia (AAH) was found in 11% and adenocarcinoma in 27% of the cases. Grade 3 PIN was associated with coincident adenocarcinoma in 39% of the cases. The prevalence of carcinoma for cases with Grade 1 and 2 PIN did not exceed that of those with Grade 0 PIN. PIN was most commonly found in association with small carcinomas. The mean age of the entire group of patients was 70.0 years, and was 69.4 years for patients with PIN without coincident carcinoma. Patients with PIN and coincident carcinoma had a mean age of 71.7 years, similar to all PIN grades, but patients with carcinoma without PIN had the highest mean age, 73.3 years. CONCLUSIONS: PIN is a common histologic finding in tissues from prostatic resections. In this study, Grade 3 PIN was strongly associated with coincident carcinoma, but lower grade PIN was not. There was no association between PIN and AAH. Patients with PIN did not appear to have a higher mean age than corresponding patients without PIN.

Immunoelectron microscopy on epoxy sections without deplasticizing to detect glomerular immunoglobulin and complement deposits in renal diseases.

Twenty renal biopsies were studied by immunoelectron microscopy (IEM) after embedding in epoxy resin. Immunogold labeling for immunoglobulins and complement C3 was performed on the epoxy sections, which were not subjected to any kind of etching or deplasticizing prior to the immunolabeling. The concentration of accelerator, DMP-30 (Tri (Dimethyl Amino Methyl) Phenol), was increased in the infiltration and embedding steps far beyond the values normally used to make immunolabeling of these antigens possible on epoxy sections. The sections were stained with tannic acid accompanied by uranyl acetate and lead citrate. Immunofluorescence (IF) for light microscopy was carried out on frozen sections of parallel tissue samples. Some cases with IgA-nephritis demonstrated a higher sensitivity for IEM than IF, in the sense that smaller amounts of antigen were detectable with IEM. Ultrastructural preservation with this method was approximately the same as that usually seen on epoxy-embedded material. By combining excellent immunolabeling with nearly optimal ultrastructural morphology in one procedure, this method is useful particularly in situations where the material available is limited, such as in studies of renal biopsies. As far as we know, this is the first time that immunoglobulins have been satisfactorily immunolabeled on epoxy sections without etching or deplasticizing.

Alpha-1-antitrypsin deficiency associated with hepatic cirrhosis and IgA nephritis.

The association between alpha1-antitrypsin (A1AT) deficiency and glomerulonephritis has only sporadically been reported, and mostly based upon autopsy findings, as opposed to the more frequent linkage between A1AT deficiency and lung emphysema with or without hepatic cirrhosis. The present case report describes a 30-year-old man with A1AT deficiency, without evidence of lung disease, who developed hepatic cirrhosis in early childhood and IgA glomerulonephritis and hypertension in adult life. The IgA nephritis followed an unusual course, with a sudden deterioration of the renal function, possibly induced by uncontrolled hypertension or the possible occurrence of vasculitis. After 6 months of hemodialysis, the patient successfully underwent living-related-donor kidney transplantation.

Nuclear texture analysis: a new prognostic tool in metastatic prostate cancer.

This report describes the prognostic value of computerized nuclear texture analysis in metastatic prostate cancer. Seventy-seven patients with histologically verified prostate carcinomas and skeletal metastases were selected from a Scandinavian multicenter study (SPCG-2). Thirty-six therapy-resistant patients experienced objective progression and cancer-related death within 2 years after orchiectomy. Thirty patients responded well to orchiectomy, i.e., showed objective disease remission and no signs of progression during 3 years of follow-up. From this data set, 10 randomly chosen therapy-resistant and 10 randomly chosen therapy-sensitive carcinomas were used in our previous study to find the optimal combination of features that can discriminate between the two groups (Yogesan et al.: Cytometry 24:268-276, 1996). In addition to these two groups, 11 patients experienced stable disease or disease remission during the first year and a secondary progression during the second or third year of follow-up, with subsequent cancer-related death. Traditional clinical prognostic factors such as histopathological grading and serum markers could not discriminate between these groups of patients. Therefore, image analysis techniques based on texture analysis have been utilized in this study of prognosis of prostate cancer. Feulgen-stained monolayers of nuclei were prepared from paraffin-embedded material taken from the primary tumor before endocrine ablation. Four different textural features were selected from the training data set to calculate the discriminating function. This function separated the therapy-sensitive and the therapy-resistant patients with 87% accuracy in the independent data set. This study demonstrates that it is possible to predict tumor progression and survival for endocrine-ablated metastatic prostate carcinomas using computerized nuclear texture analysis on light microscopy images from prostate biopsies taken at the time of diagnosis.

The theoretical relationship of immunogold labeling on acrylic sections and epoxy sections.

The purpose of this study was to predict the ratio of immunogold labeling of LR-White sections and epoxy sections using theoretical methods. Tissues used in the experiments were pancreas, pituitary, kidney, thyroid and fibrin. Antigens used as test proteins were glucagon, somatostatin, thyroglobulin, chromogranin A, ACTH (adrenocorticotropt hormone), amyloid A and fibrinogen. These are proteins of different sizes. The quotient labelingLR-White/labelingepoxy was deduced theoretically and compared to calculations based on practical immunogold experiments. The theoretically deduced formula showed acceptable correlation to these calculations. This study gives a theory--expressed mathematically--for what is happening on the molecular level at the surface of resin sections in immunoelectron microscopy. The theory explains why acrylic resins normally are better suited for immunoelectron microscopy than epoxy sections, and indicates increased usefulness of epoxy sections when the diameter of the protein carrying the epitope decreases.

Improved technique for immunoelectron microscopy. How to prepare epoxy resin to obtain approximately the same immunogold labeling for epoxy sections as for acrylic sections without any etching.

The purpose of this study was to improve the immunogold labeling of epoxy sections and to increase our knowledge of the mechanism for how antigens become immunolabeled on resin sections. Tissues from pancreas, thyroid and fibrin clots were embedded in an epoxy resin and LR-White. The epoxy mixture was composed and treated in different ways, especially with respect to altered amounts of accelerator (DMP-30). Immunogold labeling was performed with anti-glucagon, anti-thyroglobulin and anti-fibrinogen respectively. By increasing the amount of DMP-30 in the infiltration steps and/or embedding step, we observed a significant rise in the immunogold labeling. For the largest proteins the labeling was up to 8 times more intense than the labeling achieve with epoxy sections produced by 'normal' amount of accelerator in the embedding mixture and without accelerator in the infiltration mixture. For the smallest protein, glucagon, the differences were almost absent. The labeling of thyroglobulin and fibrinogen on the high accelerator epoxy sections was up to 70% of the labeling of LR-White sections, while conventional epoxy sections showed a labeling of 5-10% of that obtained with acrylic labeling. The cutting qualities of the high-accelerator blocks were similar to that of conventional epoxy embedding. The ultrastructure of the sections from the high-accelerator epoxy blocks were good, and the contrast was improved when tannic acid was used as enhancer. Our theory to explain the improved labeling is that the antigens are less tightly incorporated in the polymer network when the concentration of the accelerator is increased. The method outlined significantly improves the detectability of antigens on epoxy sections, which is the embedding resin routinely used in many laboratories.

The theoretical ratio of immunogold labeling of deplasticized epoxy sections and acrylic sections.

The purpose of this study was to predict the ratio of immunogold labeling of deplasticized epoxy sections and LR-White sections on the basis of theoretical considerations. Tissues used in experiments were pancreas, pituitary, kidney, thyroid, and fibrin. Antigens used as test proteins were glucagon, somatostatin, thyroglobulin, chromogranin A, ACTH (= Adrenocorticotropt hormone), amyloid A, and fibrinogen. These are proteins of different sizes. The quotient labelingdeplasticized/labelingLR-white was deduced theoretically and compared to measurements based on immunogold experiments to obtain a theoretical model with acceptable correlation to the measurements. This study describes a theory--expressed mathematically--for what happens at the molecular level in immunoelectron microscopy at the surface of deplasticized epoxy sections and acrylic sections. The theory explains why we normally get about the same amount of immunogold labeling using LR-White sections (acrylic resin) and deplasticized epoxy sections. Taking the nuances into account, the theory indicates increased usefulness of deplasticized epoxy sections when the diameter of the protein carrying the epitopes decreases.

Follow-up of prostatic intraepithelial neoplasia.

Biopsy or fine-needle aspiration cytology are the only appropriate methods for detection of prostatic intraepithelial neoplasia (PIN). PIN has been suggested to be a principal precursor of invasive carcinoma of the prostate. Most reports on an association of PIN and invasive prostatic cancer have a follow-up of less than 1 year, indicating that the successively diagnosed cancer most probably was present at the time of diagnosis of PIN. The natural history of PIN is unknown and detection of PIN should therefore not influence therapeutic decisions. If coexistent carcinoma is not found, close surveillance is recommended to identify a possible subsequent cancer at an early stage. Follow-up examinations should be performed at 6-month intervals for 2 years and thereafter annually.

[Investigation of palpable breast tumours. Patient flow and quality assessment of the tripple diagnostic procedure]. / Utredning av palpabel tumor mammae. Pasientstrøm og kvalitetsvurdering av trippeldiagnostikken.

The evaluation of patients with a palpable breast lump includes physical examination, mammography, and fine needle aspiration cytology. Combined use of these diagnostic procedures (triple diagnostic) gives nearly the same degree of accuracy as excisional biopsy with a sensitivity of 97-99% in patients with palpable breast carcinomas. Ultrasonography is a valuable adjunct when mammography is normal or nonconclusive and should be the primary imaging modality in patients under 35 years of age with benign findings on physical examination. Ongoing quality assessment of mammography and ultrasonography is mandatory, since the imaging modalities play a central role in the evaluation of patients with lumps in the breast. There are considerable practical problems associated with the medical audit of the triple diagnostic procedure. Aspects of the evaluation of breast lumps and organization of breast imaging centres are discussed in the light of our own experiences.

Histopathological grading and DNA ploidy as prognostic markers in metastatic prostatic cancer.

The present study compares the prognostic potential of tumour grade and DNA ploidy status in patients with advanced-stage prostatic cancer. Two outcome groups were selected on the basis of time to progression and survival after orchiectomy. A poor-outcome group consisted of 32 therapy-resistant patients who experienced disease progression during the first year after orchiectomy and subsequently death due to prostatic cancer during the following year. A good-outcome group consisted of 27 therapy-responsive patients who showed disease regression and no signs of progression during a 3 year follow-up. The primary tumours were graded twice according to WHO and Gleason classification systems by two pathologists. Final agreement between the pathologists was obtained after a consensus meeting. The analysis revealed no prognostic importance of the two histological classification systems (P = 0.62 and P = 0.70) and disclosed weak inter- and intra-observer reproducibility (kappa < 0.70). DNA ploidy analyses were performed by image cytometry on formalin-fixed, paraffin-embedded samples of the primary tumours. Overall, 48% of the tumours were diploid, 20% tetraploid and 32% anueploid. DNA ploidy status did not discriminate between the two outcome groups (P = 0.46). Histological grade and DNA ploidy showed no prognostic importance in patients with prostatic cancer and skeletal metastases.

[Alpha 1-antitrypsin deficiency--not only pulmonary and hepatic involvement]. / Alfa-1-antitrypsin-mangel--ikke bare lunge og lever.

The association between deficiency of alpha-1-antitrypsin (A1AT) and glomerulonephritis has been only sporadically reported on, as opposed to the linkage between A1AT-deficiency and lung emphysema or hepatic cirrhosis. We describe the case of a 30-year-old man with A1AT deficiency who developed hepatic cirrhosis in early childhood, and IgA glomerulonephritis and hypertension in adult life. The IgA nephritis followed an unusual course. After three years of slight elevation of serum creatinine levels, the patient rapidly developed renal failure necessitating acute hemodialysis. The deterioration of the renal function was preceded by eruption of skin lesions, believed to represent a vasculitis. After six months of hemodialysis, the patient successfully received a transplanted kidney from his mother. The literature is reviewed with respect to the association between A1AT-deficiency and renal disease. We discuss possible underlying causes for the rapid deterioration of renal function in this patient.

Mechanism for antigen detection on deplasticized epoxy sections.

The purpose of this investigation was to explain why deplasticizing of epoxy sections gives higher immunogold labeling than non-deplasticizing. The methods used were the following: (1) Comparison of the ratio of immunogold labeling of deplasticized and non-deplasticized sections with gold particles of different sizes and comparison of this ratio with respect to sections of different thickness, (2) the tilt method (Brorson et al., 1994). Human kidney tissue with amyloid A depositions, human fibrin, and human pituitary tissue were embedded, sections were deplasticized on grids, treated with anti-Aa, anti-fibrinogen or anti-ACTH (ACTH = adrenocorticotropic hormone), and reembedded on grids. Indications of significant antibody penetration were found only at the periphery of structures (ACTH-vesicles). This penetration was about 30 nm. The ratios of immunogold labeling of deplasticized and non-deplasticized sections were approximately 2, 5 and 1 for amyloid, fibrin and ACTH, respectively, and were independent of the gold particle size. No significant differences of gold labeling were found between thicker and thinner deplasticized epoxy sections regardless the gold particle size. No significant differences of gold labeling between deplasticized epoxy sections and LR-White sections were found on interior areas of ACTH-vesicles or amyloid A plaques. The increased labeling of deplasticized epoxy sections compared to normal epoxy sections seemed to be mainly a surface phenomenon. The practical significance of this observation is that deplasticizing of epoxy sections may be a better method for localizing antigens at the periphery of structures than the use of other resin embedding media. Deplasticizing of epoxy sections may be a method of choice in a pathological laboratory to detect antigens in routinely embedded tissues.

Clopidogrel--a platelet inhibitor which inhibits thrombogenesis in non-anticoagulated human blood independently of the blood flow conditions.

The goal of the present study was to investigate the effect of 7 and 14 days of daily oral administration of 75 mg clopidogrel on collagen-induced thrombogenesis in flowing non-anticoagulated human blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils positioned in a parallel-plate perfusion chamber. The wall shear rates at the collagen surface were those characteristic for veins (100 s-1), and for medium sized (650 s-1) and moderately stenosed (2600 s-1) arteries. Clopidogrel ingestion reduced the thrombus volume significantly (p < 0.05) at 100 and 2600 s-1 (39 and 51% respectively). The beta-thromboglobulin plasma levels were reduced concomitantly. However, it was not possible to measure accurately the thrombus volume at 650 s-1, due to loose packing of the platelet thrombi. Transmission electron microscopy substantiated this observation and showed that clopidogrel profoundly reduced the platelet degranulation process (p < 0.005). The inhibitory effect of clopidogrel on platelet consumption by the growing thrombi resulted apparently in higher platelet concentration at the collagen surface, which enhanced the platelet-collagen adhesion at all three shear rates (p < 0.05). Despite the low deposition of fibrin on collagen, clopidogrel reduced significantly the fibrinopeptide A plasma levels and the fibrin deposition at shear rates below 650 s-1. This was apparently a consequence of the reduced platelet recruitment and the lower activation of platelets, since activated platelets in thrombi promote deposition of fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody penetration into LR-White sections.

The purpose of this investigation is to study the ability of antibodies to penetrate sections of LR-WHITE resin. The methods used in this study were the following: (1) Reembedding of sections labeled with immunogold (1 nm) and peroxidase/DAB/gold chloride, (2) tilting of ultrathin sections treated with immunogold (1 nm), (3) immunolabeling of cylindrical structures embedded in LR-WHITE, (4) application of primary and secondary antibodies on opposite sides of ultrathin sections. Fibrin and human pituitary tissue was embedded in LR-WHITE and treated with anti-fibrinogen or anti-ACTH respectively (ACTH = Adrenocorticotropic hormone). No indication of antibody penetration into the section were found with either of the methods, contrary to findings in earlier publications. The significance of this result is that antigens cannot be demonstrated in the interior of LR-WHITE sections with post-embedding techniques. Furthermore, LR-WHITE resin may be used for quantitative immunoelectron microscopy, and the resin may be used for double immunogold labeling since the application of immunoreagents on opposite sides of the sections is completely safe.

HN-11500--a novel thromboxane A2 receptor antagonist with antithrombotic activity in humans at arterial blood flow conditions.

In the present study we have investigated the effect of a 100 mg single oral dose of a newly developed thromboxane A2 receptor antagonist on collagen-induced thrombogenesis in flowing human non-anticoagulated blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils on a cover slip placed in a parallel-plate perfusion chamber. Shear rates at the collagen surface were characteristic for medium sized (650 s-1) and moderately stenosed (2,600 s-1) arteries. Blood-collagen interactions were morphologically quantified as platelet-collagen adhesion, fibrin deposition and thrombus volume. Activation peptides of coagulation, fibrinopeptide A (FPA), and of platelets, beta-thromboglobulin (beta-TG), were measured immediately distal to the perfusion chamber. HN-11500 ingestion reduced significantly the thrombus volume by 32% at 2,600 s-1, but not at 650 s-1. However, transmission electron microscopy revealed loosely packed and less degranulated platelets at 650 s-1. The beta-TG plasma levels were also reduced at both shear rates by the HN-11500 ingestion. The platelet-collagen adhesion was significantly enhanced at both shear rates. This was apparently a consequence of higher platelet concentrations at the collagen surface, because fewer platelets were consumed by the thrombi after the drug ingestion. In contrast, the coagulation, as measured by fibrin deposition and FPA plasma levels, was not significantly affected by HN-11500. Thus, it appears that the thromboxane A2 receptor antagonist HN-11500 reduces the thrombotic response by primarily impairing the platelet function at arterial blood flow conditions, and particularly at high wall shear rates.