Kathleen Daniels

Diuretics, serum potassium and ventricular arrhythmias in the Multiple Risk Factor Intervention Trial☆

To examine the relation between diuretic use and ventricular premature complexes (VPCs) in the Multiple Risk Factor Intervention Trial, data derived from the baseline and annual rest electrocardiograms were analyzed for men in the special-intervention (SI) and usual-care (UC) groups. At baseline, age, diuretic use and presence of other rest electrocardiographic abnormalities were significantly associated with the prevalence of VPCs. Among diuretic users at baseline, those with lower serum potassium levels were most likely to have VPCs. Over the follow-up period among nonhypertensive persons the relative risk (SI/UC) for the occurrence of VPCs during follow-up was 0.83, and for hypertensives this relative risk increased linearly from 1.08 to 1.42, with higher levels of diastolic blood pressure at entry (p less than 0.01 for linear trend of relative risk estimates). This was due to an increasing risk among the SI group, and the risk was independent of the presence or absence of rest electrocardiographic abnormalities at baseline. The relative risk estimate, diuretic vs no diuretic, for development of VPCs was approximately 1.2 (p = 0.04) for SI men and 1.1 (p = 0.35) for UC men. The reduction in serum potassium level was greater for those with VPCs, and regression analysis showed that low serum potassium levels were significantly associated with the incidence of VPCs in both study groups. These data confirm and quantify the relation between diuretic drugs and VPCs and suggest that at least 1 mechanism of diuretic-induced VPCs is potassium depletion.

Randomized comparison of cyclophosphamide-total body irradiation versus busulfan-cyclophosphamide conditioning in autologous bone marrow transplantation for acute myeloid leukemia

PURPOSE This prospective trial of autologous bone marrow transplantation for acute myeloid leukemia was undertaken to compare the outcome using two different preparative regimens. METHODS AND MATERIALS Between October 1987 and April 1993, 35 patients with acute myeloid leukemia in first (n = 12) or greater (n = 23) remission were stratified by remission status and randomized to undergo 4-hydroperoxycyclophosphamide purged autologous bone marrow transplantation after either cyclophosphamide (120 mg/kg) and total body irradiation (1320 Gy in eight fractions over 4 days) (CY/TBI), or busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) (BU/CY) conditioning. RESULTS At 2 years, overall survival and disease-free survival were 39% (95% confidence intervals (CI) 22-57%) and 36% (95% CI 19-52%), respectively. Patients in first complete remission had a significantly better outcome with a 2-year disease free survival of 57% (95% CI 28-86%) compared to others at 24% (95% CI 6-43%, log rank p = 0.048). For patients conditioned with CY/TBI, the estimated 2-year disease-free survival was 50% compared to 24% for patients conditioned with BU/CY (log rank p = 0.12). Estimated 2-year relapse rates were 43% vs. 70% (log rank p = 0.17), respectively. For patients in first complete remission no differences in disease-free survival (2-year estimates 67% vs. 50%, log rank p = 0.69), between the two regimens were observed. For patients in greater than first complete remission there was a trend towards improved disease-free survival in the CY/TBI arm (2-year estimates 42% vs. 9%, log rank p = 0.06). There were no differences in time to white blood cell count (WBC) engraftment, absolute neutrophil count of > 500, incidence of bacteremias, or median time to hospital discharge between the two regimens. Acute toxicities were similar. Interstitial pneumonitis developed in two patients (one on each arm), while veno occlusive disease developed in three BU/CY patients, but none of the CY/TBI patients (log rank p = 0.07). CONCLUSIONS Cyclophosphamide-total body irradiation provided an equivalent or better outcome to BU/CY, particularly in advanced patients, and should remain the standard by which new regimens are judged. The high relapse rate with both regimens, especially patients who were in greater than in first complete remission, emphasizes the need for early transplant and for new strategies to improve outcome.

Recruitment of participants in the Lung Health Study, II: Assessment of recruiting strategies

The Lung Health Study (LHS), a multicenter randomized clinical trial of treatment to prevent chronic obstructive pulmonary disease (COPD), recruited, over a 28-month period, 5887 smokers aged 35-60 who had evidence of mild airflow obstruction on pulmonary function testing. The LHS participants were identified from a pool of over 73,000 age-eligible smokers who underwent the initial pulmonary function screening tests. Methods of recruitment in the 10 centers are here classified into five general strategies: worksites, public sites, mail/phone, media, and other. This paper deals with the results of each of these general methods and their effectiveness in producing participants eligible for the study. The most effective strategies proved to be mail/phone and media. Ongoing monitoring and a flexible approach to recruitment characterized the most successful clinics. Over the recruitment period, LHS clinics shifted their emphasis away from worksite and public site strategies and tended to focus on variations of the mail/phone strategy. Female screenees who passed first-screen eligibility criteria were more likely than males to refuse further participation.

Food metabolizability and water balance in intact and cecectomized great-horned owls

Abstract 1. 1. In great-horned owls food metabolizability, food intake and body weight were not significantly affected by cecectomy. 2. 2. Following cecectomy, water ingestion increased.

Levels of cotinine associated with long-term ad-libitum nicotine polacrilex use in a clinical trial

Studies of nicotine replacement by 2 mg nicotine polacrilex gum (NG) have typically found that one half to one third of plasma nicotine in recent smokers is replaced. This 5-year study sought to find the extent of nicotine replacement among ex-smokers in the longer term and to identify a mechanism for this relationship. The sample was the special intervention group (N = 3923) in the Lung Health Study, a controlled clinical trial involving smoking cessation. The extent of nicotine replacement was assessed by levels of salivary cotinine. Cotinine levels of ex-smokers using NG after 1 year (219 +/- 149 ng/ml) were similar to those in continuing smokers (290 +/- 159 ng/ml). After 5 years, cotinine levels were the same for NG-using ex-smokers (316 +/- 276 ng/ml), NG-using smokers (309 +/- 240 ng/ml), and NG-non-using smokers (311 +/- 198 ng/ml). Salivary cotinine among NG users at 1 year was only weakly correlated with baseline cotinine levels prior to smoking cessation. Although NG users appear to re-establish cotinine levels characteristic of their smoking, the mechanism by which this occurs remains unclear.

Determinants of induction of ventricular tachycardia in nonsustained ventricular tachycardia after myocardial infarction and the usefulness of the signal-averaged electrocardiogram

Assessment of the implications of clinical and noninvasive variables, including the results of signal-averaged electrocardiography, was performed > or = 3 weeks after myocardial infarction in 57 patients with nonsustained ventricular tachycardia (VT) who underwent programmed ventricular stimulation to guide antiarrhythmic therapy. The clinical and noninvasive parameters assessed included ages, left ventricular ejection fractions, sites of infarction, presence of akinetic or dyskinetic left ventricular segments, history of syncope, history of coronary artery bypass surgery, and presence or absence of late potentials from signal-averaged electrocardiography. Other than the presence of late potentials, no clinical or noninvasive parameters identified such persons with a significantly higher likelihood of inducible VT. When assessed as positive if 1 or more variables were abnormal, 16 of 16 (100%) patients with versus 17 of 41 without inducible VT had late potentials (p < 0.002). With more stringent criteria required (defined as prolongation of the QRS vector complex duration and low root-mean-square voltage of the terminal 40 ms of the vector complex) 8 of 16 patients (50%) with and 4 of 41 (10%) without inducible VT had late potentials recorded (p < 0.002). Thus, the signal-averaged electrocardiogram may enable identification of persons with nonsustained VT after myocardial infarction who are most likely to have VT induced at programmed ventricular stimulation.

Factors influencing respiratory rates in four species of raptors

Abstract 1. 1. Myoelectric activity associated with contractions of respiratory muscles was recorded in red-tailed hawks, American kestrels, great-horned owls, and screech owls. Resting respiratory rates were determined for all species. 2. 2. Restraint and recovery from restraint caused increases in respiratory rate. Smaller raptors had higher respiratory rates than larger ones but rates were similar in different species of comparable size. 3. 3. Gular flutter synchronized with respiration occurred in great-horned owls during recovery from restraint and adjustment to the experimental conditions.