Preoperative hemostatic activity and excessive bleeding after cardiopulmonary bypass

The rationale for predicting the risk of excessive postoperative bleeding by assessing the hemostatic status of a patient before cardiopulmonary bypass was investigated. A novel, rapid, overall test (hemostatometry) consisting of a physiologically relevant test of platelet function (shear-induced hemostasis) and coagulation was performed using nonanticoagulated blood and compared with the routine coagulation screen. Two hundred five patients undergoing elective coronary revascularization were studied 3 to 4 days before operation. Forty-nine bled excessively for nonsurgical reasons; none were predicted by the routine coagulation tests. Using a stepwise discriminant analysis, hemostatometry correctly predicted 31 of 49 (63%). Thirty of 156 predicted as bleeders by hemostatometry did not bleed. Thus, preoperative hemostatometry predicted 77% of the true outcome. The false predictions suggest, however, that certain bleeding abnormalities probably acquired during cardiopulmonary bypass cannot be predicted. These findings do not justify the routine use of preoperative tests in assessing the bleeding risk in patients undergoing cardiopulmonary bypass.     

Reconstitution of (BALB/c x B6)F1 normal mice with stem cells and thymus from nonobese diabetic mice results in autoimmune insulitis of the normal hosts' pancreases.

The NOD mouse develops immune-mediated diabetes mellitus characterized by T cell infiltration and destruction of pancreatic islet tissue. We wished to determine whether one contributing factor was an abnormality of the NOD pancreas that caused it to elicit an attack by NOD T cells. Therefore we constructed mice that had an NOD immune system and a non-NOD host pancreas. We found that these animals with only an NOD immune system developed both insulitis and diabetes in their non-NOD pancreas. We conclude that the NOD pancreas is not unique in its ability to elicit an autoimmune attack from NOD T cells.     

Circulating prostate specific antigen-positive cells correlate with metastatic prostate cancer.

Analytical flow cytometry was used to study circulating prostate specific antigen (PSA)-positive cells in 40 consecutive patients with newly diagnosed, untreated prostate cancer; 25 patients (63%) had metastatic disease confirmed by a positive bone scan. Cell suspensions were prepared for each patient from both the primary tumour and peripheral blood samples. The cells were stained with a monoclonal antibody against PSA, and analysed by flow cytometry; PSA-positive cells were sorted according to their immunofluorescence and light scatter properties. The cellular deoxyribonucleic acid (DNA) content of each specimen was also analysed to establish ploidy status. PSA-positive cells were detected in the peripheral blood of 33 patients (83%). The presence of these cells in the circulation showed a higher degree of sensitivity and specificity in predicting positive bone scans than did serum PSA levels. Circulating PSA-positive cells may represent either a subpopulation of tumour cells with distinct metastatic properties or, alternatively, host immunocytes which take up PSA in an active or passive manner.     

Parametric analysis of rank transformed data for statistical assessment of genotoxicity data with examples from cultured mammalian cells

The utility of rank transformation followed by parametric analysisof the ranks has been assessed for determination of the statisticalsignificance of genotoxicity data. Both non-parametric and parametricanalytical methods have defects when used to assess the significanceof results from routine regulatory tests. Superficially, therank transformation method followed by parametric analysis ofranks appears to be an ideal solution. However, we consideredthat such a test might suffer a substantial loss of power whenused to analyse normally distributed data with very low samplereplication. To test this hypothesis we took 22 data sets fromfive ‘borderline’ positive compounds in mouse lymphomatreat-and-plate assays where treatment-related increases werebetween 1.5- and 3-fold the control and analysed these resultsby Dunnett's t-test using rank transformed data and weighted,untransformed data. In theory these mouse lymphoma data shouldshow the rank transformation system at its worst in comparisonwith parametric methodology using weighted data. Surprisingly,the rank transformation methodology showed no loss of powerand, overall, performed more consistently than the weighteddata methodology. Based on this limited number of data sets,rank transformation followed by parametric analysis of ranksseems to be an approach very suitable for genotoxicity assaysin general, particularly where distributions are non-normalor of uncertain form. It combines the general applicabilityof non-parametric methods with the power of parametric analyses.However, the methodology still requires to be further validatedin use and by computer simulation.     

Histopathological Diagnosis of Partial and Complete Hydatidiform Mole in the First Trimester of Pregnancy

The diagnosis of molar pregnancy is a continuing diagnostic problem for many practicing histopathologists who are required to examine specimens of products of conception, particularly since changes in gynecological management in recent years have resulted in uterine evacuation at earlier gestations. The aim of this review is to provide practical, up-to-date, diagnostically useful information regarding the histological diagnosis of molar disease in early pregnancy. Pathophysiological issues relevant to molar pregnancies, such as genetic abnormalities, will be briefly summarized, but nonhistopathological aspects of molar disease will not be covered in detail in this review.