Predictive value of blood clotting tests in cardiac surgical patients.

This study prospectively evaluated numerous tests of clotting function in 897 consecutive adult cardiac surgical patients over 18 months. This included coronary operation, valve replacement, and reoperative patients. The tests included activated clotting time, activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, fibrin/fibrinogen degradation products, platelet count, and Duke's earlobe bleeding time. Other variables such as age, sex, and cardiopulmonary bypass duration were included in the multivariate analysis. Statistically significant correlations were found between 16-hour mediastinal drainage and activated partial thromboplastin time, fibrinogen, activated clotting time, fibrin/fibrinogen degradation products, platelet count, and prothrombin time. Scatter plots indicate that these relationships, although statistically significant, had little predictive value and were largely significant as a result of the large number of patients in each group, which permitted weak correlations to reach statistical significance. The best multivariate model constructed could explain only 12% of the observed variation in postoperative blood loss. Because the predictive values of the tests are so low, it does not appear sensible to screen patients routinely using these clotting tests shortly after cardiopulmonary bypass.

A randomized trial of chemotherapy (L-PAM vs CMF) and irradiation for node positive breast cancer. Eleven year follow-up of a Piedmont Oncology Association trial.

158 evaluable patients with stage II, lymph node positive, carcinoma of the breast were randomized to adjuvant therapy with either melphalan (L-PAM) or cyclophosphamide, methotrexate, and fluorouracil (CMF) after mastectomy. In addition, patients were randomized to be treated with or without post-operative irradiation therapy (RT) in addition to their chemotherapy. At a median follow-up time of 11 years, there is no difference in time to relapse (P = 0.69) or survival (P = 0.55) among the four treatment groups. Multivariate analysis including treatment arm, age, race, tumor size, histologic type, performance status, time to onset of treatment, menopausal status, and number of positive nodes, revealed that only the number of positive nodes (less than 4 vs greater than or equal to 4) was related to disease-free and overall survival. Ten year relapse-free survival for patients with less than 4 positive nodes compared to those with greater than or equal to 4 positive nodes was 63% versus 30%, and overall survival 63% versus 41%, respectively. Patients who received post-operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone (P = 0.03) but without improvement in relapse-free or overall survival. In this trial, post-operative radiation therapy when added to chemotherapy decreased the risk of local recurrence without adverse effects on survival. Treatment outcome was not influenced by chemotherapy regimen, but differences may have been obscured by the small sample size.

Cerebral hemodynamic effects of fluid resuscitation in the presence of an experimental intracranial mass.

We addressed the impact on intracranial pressure (ICP) of posthemorrhage fluid resuscitation with a protocol in which additional fluid was infused to maintain a stable cardiac output after an initial bolus of fluid was infused. Anesthetized, mechanically ventilated mongrel dogs (n = 27) underwent a 30-minute interval of hemorrhagic shock (mean arterial pressure = 55 mm Hg) during which inflation of a subdural balloon maintained ICP at 15 mm Hg. After shock, animals were resuscitated with one of four randomly assigned fluids: (1) slightly hypotonic crystalloid (Na+, 125 mEq.L-1; designated Na-125); (2) hypertonic crystalloid (Na+, 250 mEq.L-1; designated Na-250); (3) slightly hypotonic crystalloid plus 10% pentastarch (Na-125P); or (4) hypertonic crystalloid plus 10% pentastarch (Na-250P). Supplemental fluid was administered as needed to maintain cardiac output comparable to baseline values. ICP increased progressively in all fluid groups during resuscitation. Cerebral blood flow, measured by the cerebral venous outflow method, increased immediately after resuscitation and then declined steadily over time in all groups. Fluids containing pentastarch maintained hemodynamic stability with minimal supplementation throughout most of the postresuscitation period, compared with crystalloid alone, which required substantial additional volume. If decreased intracranial compliance and hemorrhage are combined, ongoing resuscitation is associated with significantly increased ICP and significantly decreased cerebral blood flow, independent of the tonicity and oncotic pressure of the infused fluid.

S-phase fraction is not correlated with nucleoside transport in acute myeloid leukemia cells.

The expression of nucleoside carrier [nitrobenzylmercaptopurine riboside (NBMPR) binding] sites has been related to proliferative fraction in cell lines and in patient myeloid and lymphoid blasts. This correlation was examined in patients with untreated acute myeloid leukemia (AML). Bone marrow blasts were incubated with 8 microM bromodeoxyuridine (BrdUrd) and dual-labeled with propidium iodide and anti-BrdUrd monoclonal antibody. Flow cytometry was used to determine the percentage of cells with detectable BrdUrd incorporation into DNA (%S) and the proliferative fraction (PF = %S+%G2M) in 63 patients; NBMPR binding sites were quantitated in samples from 29 patients. The median %S was 6.1% (range 0.6-25.9%) and the median PF was 13.0% (range 2.4-36.1%), with a median of 7243 NBMPR binding sites per cell (range 1716-27247). In contrast to a previous report which included bone marrow and peripheral blood blasts, %S in marrow blasts did not correlate with NBMPR binding sites per cell (r = 0.005, p = 0.979). Similarly, PF did not correlate with NBMPR sites per cell (r = 0.190, p = 0.325). This lack of correlation between leukemia cell proliferation and NBMPR binding sites per cell suggests that DNA synthesis in AML blasts depends primarily on de novo nucleoside synthesis rather than the usage of salvage pathways.

Bone marrow and peripheral blood findings in patients with extreme thrombocytosis. A report of 63 cases.

Sixty-three bone marrow (BM) and peripheral blood specimens from patients with platelet counts of 1000 x 10(9)/L or greater were examined in an attempt to determine if any BM or peripheral blood findings could be used reliably to distinguish primary thrombocythemia from other myeloproliferative disorders and extreme examples of reactive thrombocytosis. Our results indicated that the BM findings in primary thrombocythemia were quite similar to those in polycythemia vera and chronic granulocytic leukemia with associated extreme thrombocytosis. However, statistically significant differences between the BM findings in myeloproliferative disorders and extreme reactive thrombocytosis were found in the numbers of megakaryocytes, presence or absence of megakaryocyte clusters, stainable iron, cellularity, and reticulin content. We concluded that BM examination is a useful procedure as an aid in determining the cause of extreme thrombocytosis.

Postoperative follow-up of patients with early breast cancer. Patterns of care among clinical oncologists and a review of the literature.

Eighty clinical oncologists in the southeastern United States were surveyed to determine their strategies for follow-up care after primary treatment of early-stage breast cancer. The frequency of use of the history and physical examination, complete blood count, liver function tests, carcinoembryonic antigen levels, chest x-ray, skeletal survey, bone scan, liver scan, and mammogram for observing hypothetical low- and high-risk patients was assessed. Yearly mammograms were recommended by more than 95% of respondents. History and physical examination were the modalities used most often, whereas periodic bone and liver scans were used only in a minority of patients. A review of the literature supported the strategy of the respondents in this survey and further underscored the cost-effectiveness of the history and physical examination in detecting recurrence during follow-up. Based on this survey and supporting literature, recommendations for reasonable yet cost-conscious follow-up are presented.

The community hospital-based stroke programs in North Carolina, Oregon and New York--V. Stroke diagnosis: factors influencing the diagnostic evaluation of patients following acute stroke.

Among the 4129 patients of the Community Hospital-based Stroke Program, 30% had an unspecified stroke diagnosis. Since specific diagnosis and, perhaps, eventual treatment, derives in part from diagnostic testing, we examined the effect of clinical condition, geographic and demographic factors on the incidence of certain diagnostic tests after acute stroke. In this multivariable analysis, race, sex, history of hypertension and history of diabetes did not influence the chance of having any test, but older age strongly reduced the chances of receiving extensive evaluation. When CT scanning was available, the utilization of a CT as well as other diagnostic studies including cerebral angiography, radionuclide brain scan, EEG and EKG was increased. The odds of receiving a CT scan increased if the patient was married, and decreased with a history of previous stroke. A history of previous TIA increased the chance of having a cerebral angiogram while a history of cardiac disease decreased the chance. There were striking regional geographic differences in the use of CT, radionuclide brain scanning and cerebral angiography which may, in part, reflect differences between the availability of these technologies in urban and rural hospitals. These results indicate that evaluation of stroke patients remains heterogenous.

Weight changes in women with metastatic breast cancer treated with megestrol acetate: a comparison of standard versus high-dose therapy.

One hundred seventy-two patients with advanced breast cancer were randomized to receive 160 or 800 mg megestrol acetate per day. Patients were monitored monthly for weight, blood pressure, performance status, edema, measurement of clinically evident lesions, and toxicities. Pretreatment characteristics were similar in both arms. Weight gain was the most commonly seen side effect, with 52% of patients gaining in excess of 10 lb and 28% gaining more than 20 lb. Median weight gain for standard-dose treatment was 5 lb compared with 18 lb for high-dose treatment. There was no dose modification for excessive weight gain in any of the patients receiving the standard dose but doses were modified in 15% of those receiving high-dose megestrol acetate. Weight gains for both groups were analyzed at 30, 90, and 180 days after study entry. Treatment arm, age, prior therapy, response to prior endocrine therapy, race, performance status, dominant disease site, and number of disease sites were included in the analysis. At 30 days, patients taking high-dose megestrol acetate had a mean weight gain of 2.5 lb whereas patients taking the standard dose had stable weights. Factors predictive of weight gain were younger age (P = .0012) and fewer disease sites (P = .017). At 90 and 180 days, patients taking high-dose megestrol acetate had consistently gained more weight than those taking the standard dose (9.0 and 16.0 lb v 2.5 and 9.0 lb, respectively). Significant covariables were treatment arm (P = .0006) and younger age (P = .0211). Probability of gaining 20 lb was dependent only on treatment dose (P = .0002), and median time to a 20-lb weight gain was 217 days. Increases in systolic and diastolic blood pressures were seen in both groups, but the differences were not significant. Megestrol acetate is associated with weight gain in women with advanced breast cancer, and the amount of weight gained correlates directly with dose of megestrol acetate, length of treatment, and age of patient.

Ether-linked phosphoglyceride content of human leukemia cells.

The glycerolipids of most cells are characterized by a specific proportion of ether linkages at the sn-1 position of the glycerol backbone. A number of tumors are known to have altered concentrations of ether-linked lipids compared to normal tissues. However, no through examination of the ether-lipid content of human leukemia cells has been reported despite the importance of these lipids in normal leukocyte function. In the present study samples were obtained from adults with acute myelogenous leukemia (AML), chronic granulocytic leukemia in blast crisis, and acute lymphocytic leukemia and from healthy human donors. The cellular lipids were extracted, the individual phospholipid classes were isolated, lipid phosphorus content was determined, and the lipids were converted to diglyceride benzoate derivatives for separation and quantitation of the subclasses by high performance liquid chromatography. The data indicate that all the leukemic cells analyzed have an altered phospholipid composition compared to their respective normal leukocytes. Furthermore, among the AML patients both the percentage of the choline-containing phosphoglyceride fraction (PC) which is alkyl linked and the nmoles alkyl-PC/10(6) cells differ significantly by FAB subtype. A positive correlation between the levels of alkyl-PC and the degree of cellular differentiation is observed. Although no differences are observed between chronic granulocytic leukemia in blast crisis and AML lipids, the leukemic cells contain dramatically lower levels of alkyl-linked PC than do normal polymorphonuclear leukocytes. In contrast, no differences are observed between the alkyl-PC content of normal and leukemic lymphocytes. In light of the relations among ether-lipids, protein kinase C, and cell differentiation, these data suggest the ether-linked lipids are important in myeloid cell function and differentiation.

Accuracy of four indirect methods of blood pressure measurement, with hemodynamic correlations.

In 38 adults undergoing cardiac surgery, 4 indirect blood pressure techniques were compared with brachial arterial blood pressure at predetermined intervals before and after cardiopulmonary bypass. Indirect blood pressure measurement techniques included automated oscillometry, manual auscultation, visual onset of oscillation (flicker) and return-to-flow methods. Hemodynamic measurements or calculations included heart rate, cardiac index, stroke volume index, and systemic vascular resistance index. Indirect and intraarterial blood pressure values were compared by simple linear regression by patient and measurement period. Measurement errors (arterial minus indirect blood pressure) were calculated, and stepwise regression assessed the relationship between measurement error and heart rate, cardiac index, stroke volume index, and systemic vascular resistance index. Indirect to intraarterial blood pressure correlation coefficients varied over time, with the strongest correlations often occurring at the first and last measurement periods (preinduction and 60 minutes after cardiopulmonary bypass), particularly for systolic blood pressure. Within-patient correlations between indirect and arterial blood pressure varied widely--they were consistently high or low in some patients. In other patients, correlations were especially weak with a particular indirect blood pressure method for systolic, mean, or diastolic blood pressure; in some cases indirect blood pressure was inadequate for clinical diagnosis of acute blood pressure changes or trends. The mean correlations between indirect and direct blood pressure values were, for systolic blood pressure: 0.69 for oscillometry, 0.77 for auscultation, 0.73 for flicker, and 0.74 for return-to-flow; for mean blood pressure: 0.70 for oscillometry and 0.73 for auscultation; and for diastolic blood pressure: 0.73 for oscillometry and 0.69 for auscultation. The mean measurement errors (arterial minus indirect values) for the individual indirect blood pressure methods were, for systolic: 0 mm Hg for oscillometry, 9 mm Hg for auscultation, -5 mm Hg for flicker, 7 mm Hg for return-to-flow; for mean: -6 mm Hg for oscillometry, and -3 mm Hg for auscultation; and for diastolic: -9 mm Hg for oscillometry and -8 mm Hg for auscultation. Mean measurement error for systolic blood pressure was thus least with automated oscillometry and greatest with manual auscultation, while standard deviations ranging from 9 to 15 mm Hg confirmed the highly variable nature of single indirect blood pressure measurements. Except for oscillometric diastolic blood pressure, a combination of systemic hemodynamics (heart rate, stroke volume index, systemic vascular resistance index, and cardiac index) correlated with each indirect blood pressure measurement error, which suggests that particular numeric ranges of these variables minimize measurement error.(ABSTRACT TRUNCATED AT 400 WORDS)

Community hospital-based stroke programs in North Carolina, Oregon, and New York. IV. Stroke diagnosis and its relation to demographics, risk factors, and clinical status after stroke.

The use of diagnostic tests, the accuracy of stroke type diagnosis, and their relationship to outcome are important from the standpoint of patient management and health care costs. To address this issue, we examined the differences between stroke types in terms of demographics, risk factors, diagnostic tests, and clinical outcome in the 4,129 patients who comprise the Community Hospital-Based Stroke Program. Previous transient ischemic attacks were equally frequent among patients with embolic and those with thrombotic stroke. For all stroke types, previous stroke was as frequent as previous transient ischemic attacks. Hypertension and cardiac disease were the most common risk factors, but 10% of all stroke patients had no recognized risk factors. Intracerebral hemorrhage was most often associated with death (45%). There was a strong direct relation between in-hospital mortality and a decreased level of consciousness at admission. Overall, 30% of patients did not receive a specific stroke type diagnosis; these patients were elderly, usually nonwhite, and often had an altered level of consciousness at admission but had a risk factor profile similar to that of patients who received a specific stroke type diagnosis. In summary, our findings suggest the continued need for physician education about and refinement of stroke type diagnosis.

Use of isolated cold stress testing in determining normal lower extremity thermoregulation.

Isolated cold stress testing was performed on 72 healthy subjects in order to evaluate the normal thermoregulatory potential of vessel beds in the acral areas of the lower extremity. Two patterns of response were demonstrated: a cool response in approximately 80% of subjects, and a warm pattern in approximately 20%. In the former, the responses to cold stress were more active and the temperatures lower; in the latter, there was little change in temperature in response to the cold stress. Both patterns correlated strongly with initial temperature, and neither pattern correlated with age, sex, or smoking habits. No subjects reported pain, numbness, or discomfort during the test. This study demonstrated that wide variations in thermoregulatory flow were possible without clinical symptoms, and suggested that nutritional blood flow was adequate to meet metabolic demands despite thermoregulatory modulation.

The relation of flow cytometry to clinical and biologic characteristics in women with node negative primary breast cancer.

Flow cytometry (FC) analysis including DNA index (ploidy status) and cell kinetics (%S and %S + G2/M) was done on frozen tissue of the primary lesions of 101 women with node negative (N-) breast cancer who were studied prospectively. Currently, 19% (19/101) of the patients have recurred. No significant relations have been found between recurrence or survival and age, estrogen/progesterone receptor status, tumor size, and tumor type. The DNA index (ploidy) was not related to any clinical variable, time to recurrence, or survival. Aneuploid tumors did, however, have significantly higher %S phase activity. Patients with %S activity less than or equal to the median value were significantly different from those patients with %S above the median. They were older and had a higher frequency of ER/PR positive and well- or moderately differentiated tumors. Patients with %S + G2/M greater than the median value showed shorter time to recurrence (P = .055) and shorter survival (P = .006), whereas %S alone was significantly associated only with survival. Multivariate analysis showed that neither DNA index nor cell kinetics was significantly associated with time to relapse. DNA index was not significantly associated with survival; %S was of borderline significance whereas %S + %G2/M was a significant independent predictor of survival. Although FC data may provide independent information related to survival in N-women, additional research in a larger number of patients is needed to define its precise role in patient management.

Changes in survival after transient ischemic attacks: observations comparing the 1970s and 1980s.

We compared survival following transient ischemic attack (TIA) in 2 prospective cohorts of TIA patients admitted to Wake Forest University Medical Center. The 1st consisted of 177 patients admitted between 1961 and 1973, and the 2nd of 185 patients admitted between 1980 and 1983. Patients in the 2nd cohort had significantly greater longevity than patients in the 1st cohort, both univariately and after adjustment for cerebrovascular risk factors. The adjusted 1-year survival estimate increased from 91% in the 1st cohort to 98% in the 2nd, and the adjusted 3-year survival estimate increased from 83% in the 1st to 94% in the 2nd. The underlying causes for this dramatic improvement in survival may include early identification and aggressive management of TIAs or coexisting diseases, improved management of subsequent completed strokes or myocardial infarctions, or unadjusted differences in these cohorts. The data imply that reports of TIA survival from different periods may not be comparable.