Selection of women at high risk of breast cancer for initial screening

Selective breast cancer screening refers to the intentional restriction of screening to only a high-risk subgroup of the total population of women at risk. Using data from the Canadian National Breast Screening Study, we explored methods of defining such subgroups. Discriminants were based on risk factor information collected prior to screening and were constructed using a training group of 77 cases and 400 controls. They were then tested on a separate group of 38 cases and 200 controls. Both simple risk factor counts and logistic models were utilized and separate analyses were performed for pre- and post-menopausal women. Using a logistic model, we were able to define a high-risk subgroup encompassing less than 40% of the test controls and over 85% of the test cases. Such a selection strategy, if implemented, might reduce initial visit mammography rates by up to 60% with only a small reduction in case detection. Other uses as determining the optimal age for initiation of screening are also discussed.     

Plasmin inhibition of thrombin-induced platelet aggregation.

The effects of plasmin treatment upon washed human platelets were studied in an attempt to elucidate the mechanisms underlying thrombin-induced platelet aggregation. At calcium concentrations of 10-20 muM, PLASMIN (0.2 CTA U/ml) inhibited thrombin-induced aggregation almost completely, but did not diminish the thrombin-induced release of adenine nucleotides, 5-hydroxytryptamine, or calcium. Increasing the calcium concentration partially antagonized plasmin's inhibition of aggregation. Studies utilizing calcium chelators and the Kunitz soybean trypsin inhibitor (SBTI) as a plasmin inhibitor indicated that in order to achieve maximal block of aggregation, plasmin must act upon a substrate made fully available only after an initial thrombin-platelet interaction has taken place. Moreover, the time course of this inhibition parallels the time course of the thrombin-induced release reaction. Plasmin inhibition of aggregation could not be mimicked by exposing the platelets to proteolytic digests of fibrinogen at concentrations as high as 17% total platelet protein. Nor could inhibitory activity be recovered from supernatants of plasmin-treated platelets, upon centrifugation and treatment with SBTI. With the use of a "cold initiation" technique, the release by thrombin of 46.7 plus or minus 6.7 (mean plus or minus SEM) mu-g of fibrinogen immunological equivalents per mg platelet protein could be demonstrated. Platelets in which thrombin-induced aggregation was abolished by plasmin treatment (and the plasmin subsequently inactivated by STBI) aggregated normally upon addition of as little as 10 mu-g human plasma fibrinogen per mg platelet protein. It is concluded that plasmin inhibition of aggregation most likely results from its attack upon a protein that is released or becomes fully available subsequent to interaction of thrombin with a platelet receptor mediating release. The results of this study are consistent with a cofactor role for fibrinogen in the aggregation of human platelets by thrombin.     

Conduction system examination in a case of spontaneous heart block in a dog

This is a serial-section study of the conduction system in a 2-year-old boxer with electrocardiographic evidence of complete A-V block. The following findings were present: a lack of communication between the atria and the A-V node, atrophy of the A-V node, and tenuous connections between the A-V node and the A-V bundle. These were accompanied by acute degenerative changes in the conduction system. These changes are considered to be the result of arteriolosclerotic heart disease.     

The cardiomyopathies. A pathophysiologic approach to therapeutic management

"Cardiomyopathies" are a disparate group of myocardial disorders, usually of unknown or obscure origin, characterized by systolic or diastolic myocardial dysfunction but involving conditions of widely divergent pathophysiology. For purposes of devising appropriate clinical management, a useful classification scheme can be created with reference to the type of pathophysiologic abnormality exhibited. On this basis, three major types can be identified: (1) congestive (poor systolic function, normal diastolic function, left ventricular dilatation without the expected degree of compensatory hypertrophy), (2) hypertrophic (supernormal systolic function, subnormal diastolic function, and pronounced left ventricular hypertrophy, usually asymmetric, without dilatation), and (3) restrictive (normal or near-normal systolic function and subnormal diastolic function, usually mild symmetrical left ventricular, without dilatation). Noninvasive identification of these pathophysiologic features can be useful in optimizing management programs.     

Characteristics of presenting electrocardiograms of acute myocardial infarction from a community-based population predict short- and long-term mortality

To investigate the relevance of presenting electrocardiographic (ECG) patterns to short- and long-term mortality in nonreferral patients with acute myocardial infarction (AMI), 6 ECG patterns were analyzed. A consecutive series of 907 patients from Olmsted County, Minnesota, admitted to the Mayo Clinic Cardiac Care Unit from January 1, 1988 to March 31, 1998 for acute myocardial infarction comprised the study population. ECG patterns and distribution in the population were: (1) ST elevation alone (20.8%), (2) ST elevation with ST depression (35.2%), (3) normal or nondiagnostic electrocardiograms (18.5%), (4) ST depression alone (11.8%), (5) T-wave inversion only (10.7%), and (6) new left bundle branch block (LBBB) (3.0%). Seven- and 28-day mortalities varied significantly (p <0.01) among the 6 ECG groups. Respective mortalities were 3.0% and 6.0% for patients with normal or nondiagnostic electrocardiograms, 3.1% and 5.2% for T-wave inversion only, 7.4% and 10.6% for ST elevation alone, 9.4% and 13.1% for ST depression alone, 10.3% and 13.8% for ST elevation with ST depression, and 18.5% and 22.2% for new LBBB. Length of hospital stay (LOS) also varied among the ECG pattern groups (p <0.001) with the longest average LOS being in the new LBBB group (12.5 days). Long-term survival was similar among 5 ECG pattern groups (45% to 55% at 8 years from discharge) with the exception of LBBB (20% at 8 years). Among non-LBBB groups, ST-segment depression with or without ST elevation was associated with increased short-term mortality. Also, in this community-based population, 18.5% of patients had normal or nondiagnostic electrocardiograms.     

Treatment of end-stage diabetic nephropathy: over a decade of experience at one institution

Results of treatment of end-stage renal disease in 139 patients with diabetes mellitus revealed survival of 76% at 1 year and 48% at 5 years. These results compare favorably with other reports from Europe and the United States, probably because of the greater number of patients receiving renal transplants, and possibly because of the use of continuous ambulatory peritoneal dialysis as a recent treatment modality. Patients not receiving transplants were much older (mean age, 47.8 years) than those receiving transplants. Of those not given transplants, survival was best on CAPD. Comparison of those surviving at least 3 years was made with those expiring in the first year. Long-term survivors were younger, had diabetes for a shorter period, but had higher mean blood pressures and serum creatinine values than short-term survivors. Short-term survivors also had over a 50% incidence of prior myocardial infarction or cardiorespiratory arrest, while no long-term survivors had such a history. Long-term survivors were also more likely to have received a transplant, and short-term survivors were more likely to have received intermittent peritoneal dialysis or hemodialysis. A transplant from a living related donor is the treatment of choice for diabetics under age 40 and perhaps for older patients as well. The choice among CAPD, hemodialysis and cadaver transplant requires consideration of many factors.     

Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon

Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti-idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti-idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.     

Accelerated cardiovascular disease and myocardial infarction risk in patients with the human immunodeficiency virus

Highly active antiretroviral therapy has greatly reduced mortality among human immunodeficiency virus (HIV)-infected patients by delaying, and possibly preventing, progression to AIDS. The risk of cardiovascular disease (CVD) is now an important consideration in these patients and may increase as they live longer. Risk factors for CVD, the inflammatory effects of HIV, and the metabolic complications of antiretroviral therapy may accelerate the onset of CVD. Death from myocardial infarction, however, is still rare compared with death from progression of HIV disease, and the benefits of antiretroviral therapy clearly outweigh any associated risk of CVD. In this review, the authors describe the risk of accelerated CVD in HIV-infected individuals, the proposed viral and therapy-related mechanisms of CVD, the clinical features of CVD in these patients, and monitoring and management guidelines to reduce CVD risk. Identifying, monitoring, and treating CVD risk factors in HIV-positive patients is vital to improving their lives and should become standard practice.     

Use of the day 6 bone marrow to alter remission induction therapy in patients with acute myeloid leukaemia: a leukemia intergroup study

Patients with acute myeloid leukaemia who fail to show substantial bone marrow cytoreduction by day 6 of induction therapy enter complete remission (CR) less frequently than patients with good bone marrow leukaemic cytoreduction. The objective of the current study was to determine whether an increase in the intensity of therapy on days 8, 9 and 10 ('augmentation' of remission induction therapy) for patients with poor bone marrow cytoreduction detected in the day 6 bone marrow could improve the complete remission rate without increasing the number of toxic deaths. Patients from six centres were entered and treated with standard dose ara-C for 7 or 10 d and an anthracycline for the first 3 d. Patients aged less than 60 years and with greater than 30% bone marrow biopsy cellularity or greater than 10% abnormal cells on the aspirate obtained 6 d after the start of therapy were augmented with cytosine arabinoside 3 g/m2 every 12 h on days 8, 9 and 10. Therapy was augmented in 116 of the 252 patients less than 60 years. There was a highly statistically significant difference between augmented and nonaugmented patients (P less than 0.001) for the per cent biopsy cellularity and per cent abnormal cells in the day 6 marrow. The CR rate for augmented patients was 69% and for nonaugmented patients 60% suggesting that augmentation therapy abrogated the prognostic significance of more extensive residual leukaemia in the day 6 bone marrow. The results suggest that augmentation of remission induction for patients with poor bone marrow cytoreduction detected 6 d after initiation of therapy, may salvage patients who are destined to fail remission induction because of resistant disease without producing excessive toxicity.