Pulmonary embolism causes endomyocarditis in the human heart.

BACKGROUND: Pulmonary embolism (PE) is a significant cause of morbidity and mortality. In a recent study in patients with PE, an increased level of macrophages was found in the right ventricle. OBJECTIVE: To evaluate the presence of inflammatory cells, myocytolysis and intracavitary thrombi in the left and right ventricle of patients who died because of PE as a putative new source of heart failure. PATIENTS AND METHODS: 22 patients with PE were studied. For comparison, eight controls and 11 patients who died of chronic pulmonary hypertension (PHT) were used. Slides of the left and right ventricle were stained with antibodies, identifying neutrophilic granulocytes, lymphocytes and macrophages, which were subsequently quantified. Myocytolysis was visualised using complement staining. Thrombi were identified by conventional staining. RESULTS: Compared with controls, in patients with PE a significant increase in extravascular localisation of all three inflammatory cells was found both in the right and left ventricle, coinciding with myocytolysis, indicative for myocarditis. No increase in inflammatory cells was found in patients with PHT. Endocardial cellular infiltration was also found, partly coinciding with the presence of ventricular thrombi. CONCLUSIONS: In patients with PE, endomyocarditis and intracavitary thrombi in the left and right ventricle were found. These abnormalities may be an additional new explanation for the observed cardiac enzyme release and functional abnormalities of the heart in these patients and may contribute to the morbidity and mortality of the disease.

Macronodular adrenocortical hyperplasia in a postmenopausal woman.

This case report describes the diagnosis of Cushing's syndrome due to macronodular adrenal hyperplasia in an elderly woman who presented with fatigue, muscle weakness and oedema, and recent excessive bruising. Long-standing disease and comorbidity precluded adrenalectomy. Despite treatment with metyrapone and diuretics, the patient died after two months hospitalisation. Postmortal examination revealed overexpression of luteinising hormone (LH) receptors in the adrenal glands, suggesting that the postmenopausal rise in LH may have a role in adrenal hyperplasia and hypercortisolism.

Relationship between the presence of oncogenic HPV DNA assessed by polymerase chain reaction and Ki-67 immunoquantitative features in cervical intraepithelial neoplasia.

The aims of this study were firstly to determine which Ki-67 immunoquantitative parameters correlate with the presence of oncogenic human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions; and secondly to compare prospectively the routinely assessed CIN grades with the Ki-67 quantitative pathological CIN grade, the expert revised grade, and the presence of oncogenic HPV DNA. HPV polymerase chain reaction (PCR) and Ki-67 immunoquantitation were performed on 90 consecutive biopsies (16 CIN 1, 35 CIN 2, and 39 CIN 3). CIN grade was assessed routinely by six different pathologists. The presence of the lesion was confirmed in a histological section following the material used for PCR and Ki-67 analysis. In a second prospective routine test set analysis, 66 more CIN lesions (14 CIN 1, 15 CIN 2, and 37 CIN 3) were routinely graded (also by six different pathologists, routine CIN grade=CIN(ROUT)), studied for oncogenic HPV DNA, and graded by quantitative Ki-67 features (quantitative pathological CIN grade=CIN(QP)). These latter cases were blindly revised by one of the authors (reference CIN grade=CIN(REF)). Eight of the nine Ki-67 immunoquantitative features showed a significant difference between the oncogenic HPV-positive and -negative cases. The best single discriminator was the 90th percentile of the stratification index (SI90). All 61 cases with Ki-67 SI90>0.60 were HPV-positive (68% of the total group studied). Of the 29 cases with SI90< or =0.60, 16 were negative and 13 positive for oncogenic HPV and none of the Ki-67 features (either single or combined) could distinguish them. Using stepwise multivariate analysis, the best discriminating combination of features was SI90 and the percentage of Ki-67-positive nuclei in the deep third layer of the epithelium (PERC DL). The combination of SI90 and the percentage of Ki-67-positive nuclei per 100 microm basal membrane was nearly as strong as that of SI90 and PERC DL. With these two features, 86% of the cases were correctly classified. The subjective estimate of SI90 (>0.60 or < or =0.60) by two independent observers was not accurate and not reproducible. In the prospective routine test set analysis of 66 cases, the 37 CIN(ROUT)=3 all had CIN(QP) and CIN(REF)=3 and all these cases were oncogenic HPV-positive. Eight of the 14 original CIN(ROUT)=1 grades were oncogenic HPV (=HPV)-positive and five of these eight were upgraded by CIN(QP) to CIN 2 and CIN 3. These upgrades were in agreement with the blind reference revisions. The six HPV-negative CIN(ROUT)=1 cases were CIN 1 both by CIN(QP) and by CIN(REF). Thirteen of the 15 original CIN(ROUT)=2 grades were HPV-positive and seven of these were CIN(QP)=3. All six HPV-positive CIN(ROUT)=2 cases that were CIN(QP)=2 were also CIN(REF)=2 at blind revision. In conclusion, this study has shown firstly, that in CIN lesions, Ki-67 immunoquantitative features and the presence of oncogenic HPV are highly correlated, and also within one subjective CIN grade; secondly, that subjective impressions of SI90 are not as accurate or reproducible as quantitative image analysis results; and thirdly, that the routine application of QP CIN-grading gives results that are in very good agreement with CIN grades assessed by an expert. Thus, routine QP-grading may be used to correct the subjective grade assessed by non-expert pathologists.

Leukocyte migration in experimental inflammatory bowel disease.

Emigration of leukocytes from the circulation into tissue by transendothelial migration, is mediated subsequently by adhesion molecules such as selectins, chemokines and integrins. This multistep paradigm, with multiple molecular choices at each step, provides a diversity in signals. The influx of neutrophils, monocytes and lymphocytes into inflamed tissue is important in the pathogenesis of chronic inflammatory bowel disease. The importance of each of these groups of adhesion molecules in chronic inflammatory bowel disease, either in human disease or in animal models, will be discussed below. Furthermore, the possibilities of blocking these different steps in the process of leukocyte extravasation in an attempt to prevent further tissue damage, will be taken into account.