Analysis of possible triggers of acute myocardial infarction (the MILIS study)

Recent documentation of a circadian variation in acute myocardial infarction (AMI) suggests that AMI is not a random event, but may frequently result from identifiable triggering activities. The possible triggers reported by 849 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size were analyzed. Possible triggers were identified by 48.5% of the population; the most common were emotional upset (18.4%) and moderate physical activity (14.1%). Multiple possible triggers were reported by 13% of the population. Younger patients, men and those without diabetes mellitus were more likely to report a possible trigger than were older patients, women and those with diabetes. The likelihood of reporting a trigger was not affected by infarct size. This study suggests that potentially identifiable triggers may play an important role in AMI. Because potential triggering activities are common in persons with coronary artery disease, yet infrequently result in AMI, further studies are needed to identify (1) the circumstances in which a potential trigger may cause an event, (2) the specific nature of potential triggering activites, (3) the frequency of such activities in individuals who do not develop AMI and (4) the presence or absence of identifiable triggers in various subgroups of patients with infarction.     

Correlation of P-glycoprotein expression and function in childhood acute leukemia: a children's cancer group study

Clinical drug resistance may be attributed to the simultaneous selection and expression of genes modulating the uptake and metabolism of chemotherapeutic agents. P-glycoprotein (P-gp) functions as a membrane-associated drug efflux pump whose increased expression results in resistance to anthracyclines, epipodophyllotoxins, vinca alkaloids, and some alkylating agents. This type of resistance occurs as both de novo and acquired resistance to therapy for leukemia. We have studied P- gp expression and function in childhood acute leukemias by developing a series of doxorubicin- and vincristine-selected CEM, T-cell lymphoblastoid cell lines that recapitulate the low levels of expression and resistance seen clinically. These cell lines have been used to develop flow cytometric assays for the semiquantitative measurements of P-gp expression with the MRK16 monoclonal antibody and P-gp function using the enhanced retention of rhodamine 123 in the presence of verapamil, a resistance modulator. Kolmogorov-Smirnov statistics, represented by the D measurement, are used to determine the difference in level of P-gp expression by comparing MRK16 staining to an IgG2a isotype control. When D is > 0.09, there is an excellent correlation (R = 0.82) between P-gp expression and function. The evaluation of 107 bone marrow specimens from 84 children with lymphoblastic or myelogenous leukemia showed a statistically significant (P = .004) increase in P-gp function at relapse. P-gp expression at relapse, however, approached but did not reach a significant level (P = .097). Using this methodology, we can identify patients with levels of P-gp expression and function that we can define clinically, as well as children with discordant multidrug resistance phenotypes. This study supports the role of P-gp-mediated drug resistance in childhood leukemia and confirms that P-gp expression and function are measurable in their leukemic blasts. These assays provide the means for the in vitro testing of resistance modulators and the monitoring of in vivo response to treatment with these agents.     

Coffee and coronary heart disease

Background: The role of coffee consumption in the onset of myocardial infarction remains uncertain. A review of published reports showed that although cohort data suggest very little excess risk of coronary heart disease among habitual coffee drinkers, case-control data suggest an excess risk of the order of 60% for people drinking five or more cups per day.

Methods: We obtained as much information as possible on the lifestyle and habits, including coffee consumption, of people admitted with chest pain to the Coronary Care Unit at the Royal Perth Hospital, Australia. A questionnaire was given to them by the attending nursing staff. Details were recorded by the patient, often with help from the nursing staff. A similar questionnaire was completed by patients attending the Cardiology Outpatient Clinic.

Results: One of the outstanding differences between the 182 patients with myocardial infarction or unstable angina and 185 patients with chronic stable coronary heart disease who filled in forms while waiting in the Cardiology Outpatient Clinic was that more people with acute coronary syndromes were drinking in excess of five cups of coffee per day (18 vs 7.5%; P = 0.003). In logistic regression analysis adjusted for age, smoking status (past and current), hypertension, dyslipidaemia and diabetes, the odds ratio was 2.51 (95% CI 1.43,4.43; P = 0.021).

Conclusion: The present case-control study provides evidence for an increased risk of myocardial infarction or unstable angina among individuals drinking more than five cups of coffee per day.     

Prognosis after cardiac arrest due to ventricular tachycardia or ventricular fibrillation associated with acute myocardial infarction (the MILIS Study). Multicenter Investigation of the Limitation of Infarct Size

Previous studies have reached conflicting conclusions about whether cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF) in acute myocardial infarction (AMI) is of long-term prognostic significance. The mortality rate in 849 patients with confirmed AMI was analyzed. The mortality rate during the initial hospitalization was higher for patients in whom VT/VF occurred (27% vs 7%, p less than 0.001). The in-hospital mortality rate for patients with primary VT/VF, that is, VT/VF occurring in the absence of hypotension or heart failure, was similar to that of patients who did not have VT/VF (8% vs 7%, difference not significant), whereas the rate for patients with secondary VT/VF was significantly greater than that for patients with no VT/VF (51% vs 7%, p less than 0.001). The timing of occurrence of VT/VF also influenced mortality: Patients in whom VT/VF occurred more than 72 hours after admission had a higher in-hospital mortality rate than did patients in whom it occurred within 72 hours (57% vs 20%, p less than 0.05). All cases of primary VT/VF occurred within the first 72 hours of admission. The long-term mortality rate for hospital survivors was not significantly different for patients who had had VT/VF during acute infarction compared with those who had not (19% vs 21%) (mean follow-up 32 months). Thus, cardiac arrest due to ventricular tachyarrhythmia was associated with a higher in-hospital mortality rate but was not a prognostic factor among hospital survivors. Patients resuscitated from primary VT/VF, which characteristically occurs early after AMI, do not have an adverse prognosis.     

Prognostic significance of the Karnofsky Performance Status score in patients with acute myocardial infarction: comparison with the left ventricular ejection fraction and the exercise treadmill test performance. The MILIS Study Group

The prognostic significance of functional status has not been previously studied in the setting of acute myocardial infarction. We assessed the Karnofsky Performance Status (KPS) score, a simple functional status scale that is commonly used to categorize physical ability, in 849 patients with acute myocardial infarction who were enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study. We then compared the KPS score with other predictors of prognosis in these patients. In patients who presented with acute myocardial infarction, a lower KPS score (less than 8 on a scale of 1 to 10) 3 weeks before the index infarction was associated with a higher incidence of congestive heart failure, in-hospital cardiac arrest, and mortality during hospitalization, as compared with patients with KPS scores greater than or equal to 8 (each p less than 0.001). Cumulative 1-year and 4-year mortality rates were significantly higher in patients with KPS scores less than 8, as compared with patients with KPS scores greater than or equal to 8 (42.5% vs. 12.6% at 1 year and 61.6% vs 25.1% at 4 years, respectively; both p less than 0.001). The left ventricular ejection fraction on admission was significantly lower in patients with KPS scores less than 8, as compared with those with KPS scores greater than or equal to 8 (p less than 0.019). The cumulative mortality rate was equally well predicted by low KPS score and by left ventricular ejection fraction (both p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

A method for simultaneous study of the karyotype, morphology, and immunologic phenotype of mitotic cells in hematologic malignancies

A major problem in the cytogenetic analysis of hematologic neoplasms has been an inability to identify the cell from which the chromosomes were obtained. We describe a procedure that allows simultaneous analysis of karyotype and cell cytology in mitotic cells. The method differs from conventional cytogenetic analysis in that after mild hypotonic treatment, the cells are cytocentrifuged onto glass slides. In mitotic cells, this procedure often results in adequate spread of the chromosomes within the intact cell membrane. The cytoplasmic structure also remains intact, so that cytologic preparations are of good quality. Morphologic and immunologic identification of mitotic cells can be done using routine hematologic stains, such as Giemsa or Sudan black B, and various antisera using immunofluorescence techniques. The chromosomes can be simultaneously analyzed either without banding on slides stained with Giemsa or with Q-banding on slides stained with immunofluorescence techniques. Identification of numerical and structural karyotype aberrations thus is possible in morphologically identified cells.