Enolase isoenzymes. II. Hybridization studies, developmental and phylogenetic aspects.

1. Hybridization studies have been carried out in vitro using mixtures of partially purified isoenzymes 1 and 3 of rat enolase (2-phospho-D-glycerate hydrolyase, EC 4.1.1.11). Immunological methods were used to demonstrate the formation of the hybrid. 2. Immunological analysis of the elution peaks from QAE-Sephadex chromatography of heart enolase indicates the occurrence in vivo of the hybrid enolase 2. 3. Developmental changes in the proportions of isoenzymes 1, 2 and 3 in heart and skeletal muscle of rat have been studied quantitatively. In both tissues isoenzyme 1 predominates in the foetus, but is partially replaced by 2 and 3 in adult heart and completely by 3 in the adult muscle. 4. Evidence is given of the binomial distribution of the proportions of the three isoenzymes in the developing heart. 5. Phylogenetic studies of the immunological properties of enolases from muscle, liver and heart have been carried out. 6. It is concluded that the three isoenzymes arise from two independent genetic loci and it is suggested that these evolved from a common ancestral gene 200-300 million years ago.

Enolase isoenzymes. III. Chromatographic and immunological characteristics of rat brain enolase.

1. The chromatography of rat brain enolase (2-phospho-D-glycerate hydrolyase, EC 4.2.1.11) reveals three distinet components. One of these appears to be isoenzyme 1 (alpha alpha) but isoenzymes 2 (alpha beta) and 3 (beta beta) are absent. 2. The most acidic form of brain enolase was partially purified and an antiserum raised against it in the chicken. 3. a combination of chromatographic and immunological studies showed that a third type of subunit (gamma) is present in the brain giving rise to two further isoenzymes (alpha gamma and gamma gamma). 4. Developmental studies on the brain enzyme show an increase in total enolase activity from foetal life to maturity and a concurrent rise in the proportion of brain specific dimers. 5. It is therefore concluded that there are three genetic loci alpha, beta and gamma, coding for the enolase isoenzymes of rat tissues.

High rates of sustained smoking cessation in women hospitalized with cardiovascular disease: the Women's Initiative for Nonsmoking (WINS).

BACKGROUND: Although men hospitalized with cardiovascular disease (CVD) show high smoking-cessation rates, similar data for women are lacking. We tested the efficacy of smoking-cessation intervention in women hospitalized for CVD. METHODS AND RESULTS: In this randomized controlled trial conducted from 1996 to 2001, 277 women diagnosed with CVD (mean age 61+/-10 years) were randomly assigned within 1 of 12 San Francisco Bay Area hospitals to a usual-care group (UG; n=135) or intervention group (IG; n=142). Baseline histories were obtained, and interviews to ascertain self-reported smoking status occurred at 6, 12, 24, and 30 months after hospitalization. The UG received strong physician's advice, a self-help pamphlet, and a list of community resources. The IG received strong physician's advice and a nurse-managed cognitive behavioral relapse-prevention intervention at bedside, with telephone contact at intervals after discharge. The groups were similar demographically and had smoked cigarettes for a median of 38 (IG) or 40 (UG) years. Time to resumption of continuous smoking was assessed by Kaplan-Meier analysis, and risk differences between groups were determined. Time smoke-free was significantly greater for the IG than the UG (P=0.038). Point prevalence for nonsmoking at the interviews was somewhat greater for the IG than the UG (P>0.15 at all times). CONCLUSIONS: Cognitive behavioral intervention resulted in longer average times to resumption of smoking, but in these 2 groups of older women with limited social and financial resources, long-term success rates were similar. Systematic identification of smokers and even the brief intervention afforded the UG yielded a high smoking-cessation rate over time.

Relaxation therapy and high blood pressure.

Thirty-one patients receiving medical treatment for essential hypertension were randomly distributed into three groups: (1) relaxation therapy, (2) nonspecific therapy, and (3) medical treatment only. The nonspecific therapy group spent the same amount of time with the therapists as the relaxation group but was not given a specific therapy. Blood pressures were measured at a different time and in a different place from the behavioral treatments. The relaxation therapy group showed a significant reduction in blood pressure postreatment compared with the nonspecific therapy and medical treatment only groups, even when those patients whose medication was increased were excluded from the data analysis. At follow-up six months post-treatment, the relaxation group showed a slight decrement in treatment effects, while both the nonspecific therapy and medical treatment only groups showed continued improvement; thus, there was not a significant difference between groups.

Relaxation training. Blood pressure lowering during the working day.

Controlled studies have demonstrated that relaxation training can lead to significant in-clinic blood pressure (BP) reductions in patients with essential hypertension. We examined the BP-lowering effect of relaxation training during the working day. Forty-two patients being treated for essential hypertension with diastolic BPs greater than 90 mm Hg were randomized into either a relaxation training program or no treatment. Multiple BP measurements were made during the working hours, using an ambulatory monitoring device, before and after training. Significant work-site differences between groups were evident after treatment both for systolic and diastolic pressures. These results suggest that relaxation therapy leads to a reduction in BP that is evident in the natural environment, providing new evidence that the procedure is a useful adjunct to the treatment of hypertensive patients.

Stress test reactivity in panic disorder.

The psychological and physiological reactivity of 52 patients with panic disorder to mental arithmetic, cold pressor, and 5% carbon dioxide inhalation tests was compared with that of 26 age- and sex-matched normal subjects. In general, patients with panic disorder were neither more physiologically reactive to these stressors than normal subjects nor slower to recover from them, but they were tonically more anxious and much more likely to ask to stop carbon dioxide inhalation or to report panic attacks during this test. Patients who reported panic attacks (46%) had manifested greater anticipatory anxiety before the gas was delivered, accompanied with increased beta-adrenergic cardiac tone. Thus, anticipatory anxiety can be an important factor in panic provocation. Physiological measures varied greatly in their sensitivity to phasic or tonic anxiety. Carbon dioxide stimulated large increases in respiratory minute volume, but these increases were no greater for patients than for normal subjects.

Childhood leukemia: cerebrospinal fluid enolase isoenzymes in central nervous system infiltration.

Enolase isoenzymes were measured in the cerebrospinal fluid of seven consecutive children with lymphoblastic leukemia who developed meningeal (CNS) leukemia. Assays were performed at the time CNS disease was discovered and during the subsequent 4 weeks. Three of the seven were also examined 1-3 months before CNS relapse was confirmed. Fourteen children on similar systemic therapy without CNS infiltration served as controls. Prior to and at the onset of CNS disease alpha enolase was elevated in all patients studied. The gamma form was raised in only one beforehand and only three at the time of relapse. The alpha isoenzyme was related to the blast cell count and fell during therapy in all but one child, whereas the gamma was not and showed no significant change. The three patients with raised gamma enolase were the only children with other than common lymphoblastic leukemia. There was no clear indication whether either enzyme concentration had any importance in terms of disease outcome, although one child developed a further CNS relapse 10 months later. He was the only patient whose alpha enolase rose following intrathecal methotrexate. Neuronal disruption due to common lymphoblastic leukemia in the CNS appears to be minimal. Other types of leukemia may give rise to more neuronal damage. The alpha isoenzyme, from glial tissue and malignant cells, may be elevated even in the absence of detectable blasts in the cerebrospinal fluid and may be a sensitive marker of CNS infiltration in such circumstances.

Smoking in older women. Is being female a 'risk factor' for continued cigarette use?

Current national data indicate that a greater percentage of women entering their fifth and sixth decades of life are current, as opposed to former, smokers, while for men the opposite pattern is present. A representative sample of 1876 men and women aged 50 to 65 years living in a northern California community were interviewed to examine factors related to gender differences in quit rates in this age group. In this well-educated community, a significantly greater percentage of women (25.6%) continued to smoke relative to men (18.6%), with a greater percentage of men reporting being former smokers. Multivariate analysis revealed educational level and marital status, rather than gender, to be significant, Independent factors associated both with current cigarette use and with successful quitting. Our data indicate that it is not being female per se, but rather the disparities in educational level and marital status that are linked with being an older woman, that are associated with continued smoking in this age group. In light of this, delivery of relevant information and support on the part of physicians and other health professionals may be of particular use to this population segment.

Smoking cessation in hospitalized patients. Results of a randomized trial.

BACKGROUND: Few research studies have evaluated the effectiveness of smoking interventions in hospitalized patients. This randomized controlled trial compared the efficacy of 2 smoking cessation programs in patients hospitalized in 4 community hospitals in a large health maintenance organization within the San Francisco Bay Area in California. METHODS: Patients were randomly assigned to usual care (n = 990), nurse-mediated, behaviorally oriented inpatient counseling focused on relapse prevention with 1 postdischarge telephone contact (minimal intervention, n = 473), or the same inpatient counseling with 4 postdischarge telephone contacts (intensive intervention, n = 561). The main outcome measure, smoking cessation rate, was corroborated by plasma cotinine determination or family confirmation, 1 year after enrollment. RESULTS: At 1 year smoking cessation rates were 27%, 22%, and 20% for intensive intervention, minimal intervention, and usual care groups, respectively (P = .009 for intensive vs usual care). Subgroup analyses by diagnosis revealed that the odds of cessation among patients with cardiovascular disease or other internal medical conditions were greater among those receiving the intensive intervention than among their counterparts receiving usual care (odds ratios, 1.6 and 2.0, respectively). CONCLUSIONS: A multicomponent smoking cessation program consisting of physician advice; in-hospital, nurse-mediated counseling; and multiple postdischarge telephone contacts was effective in increasing smoking cessation rates among hospitalized smokers. Hospital-wide smoking cessation programs could substantially increase the effectiveness of hospital smoking bans.

Chronic disease management: treating the patient with disease(s) vs treating disease(s) in the patient.

The treatment of chronic disease is often complicated by the coexistence of multiple medical conditions and by the presence of social and psychological impediments. The needs posed by patients with chronic disease are overwhelming the capacity of the American health care system. Alternative disease management systems that rely on specially trained nurse case managers to implement detailed clinical protocols, including drug algorithms, have shown efficacy in managing chronic medical conditions, singly and in combination. By fostering integration of care across subspecialty and medical-social boundaries, such systems enable treatment of the patient with disease(s), not simply treatment of disease(s) in the patient. Working closely with primary care physicians, often by telephone-mediated interaction with patients, nurse case managers may take an expanded role in meeting the challenges posed by chronic disease.

Report of the health care delivery work group: behavioral research related to the establishment of a chronic disease model for diabetes care.

As one of four work groups for the November 1999 conference on Behavioral Science Research in Diabetes, sponsored by the National Institute on Diabetes and Digestive and Kidney Diseases, the health care delivery work group evaluated the status of research on quality of care, patient-provider interactions, and health care systems' innovations related to improved diabetes outcomes. In addition, we made recommendations for future research. In this article, which was developed and modified at the November conference by experts in health care delivery, diabetes and behavioral science, we summarize the literature on patient-provider interactions, diabetes care and self-management support among underserved and minority populations, and implementation of chronic care management systems for diabetes. We conclude that, although the quality of care provided to the vast majority of diabetic patients is problematic, this is principally not the fault of either individual patients or health care professionals. Rather, it is a systems issue emanating from the acute illness model of care, which still predominates. Examples of proactive population-based chronic care management programs incorporating behavioral principles are discussed. The article concludes by identifying barriers to the establishment of a chronic care model (e.g., lack of supportive policies, understanding of population-based management, and information systems) and priorities for future research in this area needed to overcome these barriers.

Insulin-like growth factor-I as a reflection of body composition, nutrition, and puberty in sixth and seventh grade girls.

Large variations in nutritional intake have profound effects on the GH-insulin-like growth factor-I (IGF-I) axis in children and adults, but the effect of normal variations in nutrition on IGF-I concentrations is largely unstudied, particularly during puberty. We measured serum IGF-I concentrations in 325 sixth and seventh grade girls (12.4 +/- 0.7 yr) at the beginning of a multisite school-based health curriculum. The mean serum IGF-I level among the 243 girls with complete data was 573 +/- 244 micrograms/L. Pubertal stage was significantly associated with IGF-I (P less than 0.0001, by analysis of variance). Mean concentrations rose from 427 +/- 198 micrograms/L among those at the earliest pubertal stages to 639 +/- 219 micrograms/L among the mature girls. After adjusting for the association with the stage of pubertal development, serum IGF-I was not significantly associated with measures of body composition (body mass index, triceps skin fold thickness, waist/hip ratio, height, and weight). Additionally, IGF-I concentrations were not associated with nutritional intake (total calories, total protein, total fat, and total carbohydrate) or such measures of nutrition as serum iron, hemoglobin, red cell mean corpuscular volume, white cell count, and cholesterol. IGF-I concentrations, however, were significantly correlated with transferrin concentrations, another possible index of nutritional status (r = 0.29; P less than 0.0001). IGF-I is not a clinically useful index of nutritional status among normal pubertal girls.

Skin conductance habituation in panic disorder patients.

Skin conductance habituation was compared between 38 patients meeting DSM-III criteria for Panic Disorder and 29 normal controls. Approximately half of each group was randomly assigned to be given 100 dB SPL tones and the other half 75 dB tones. All indices pointed to slowed habituation in patients compared with normals: number of trials to response habituation, total number of responses, and slope of decline of skin conductance level. Patient-normal differences were not significantly larger for 100 dB than for 75 dB. In addition, patients compared with normals had more nonspecific fluctuations, higher skin conductance levels, and a shorter response latency to the first stimulus. Stepwise discriminant analyses classified patients and normals better in the 100 dB than in the 75 dB condition, and showed that the various skin conductancy variables were largely redundant at the higher intensity.

Imipramine and alprazolam effects on stress test reactivity in panic disorder.

The reactivity of 40 panic disorder patients on mental arithmetic, cold pressor, and 5% CO2 inhalation stressors was tested before and after 8 weeks of treatment with imipramine, alprazolam, or placebo. Mean levels of subjective and physiological stress measures were compared during a baseline before any stressors were given, and at anticipation, stressor, and recovery periods for each stressor. After treatment, imipramine patients differed from the other two treatment groups on the prestressor baseline in showing higher systolic blood pressure (mean difference about 10 mmHg), higher diastolic blood pressure (10 mm Hg), higher heart rate (15 bpm), less respiratory sinus arrhythmia, shorter pulse transit time, and lower T-wave amplitude. Respiratory measures, electrodermal measures, body movement, and self-reported anxiety and excitement did not distinguish the groups. Reactivity to the stress tests was unaffected by the medications, but tonic differences present in the baseline persisted.

Autonomic characteristics of agoraphobia with panic attacks.

We compared electrodermal and heart rate measures of autonomic activation between patients meeting DSM-III criteria for agoraphobia with panic attacks and controls in terms of tonic level, reactivity to various types of stimuli, recovery, habituation, and spontaneous variability. The most striking differences between groups in the laboratory were higher tonic levels of skin conductance and heart rate among patients. Patients' heart rates were also tonically elevated in a test situation outside the laboratory. Certain measures of habituation and spontaneous variability also differed between groups, but there were only weak and inconsistent differences in reactivity to, or recovery from, stimuli with diverse qualities of novelty, startlingness, intensity, or phobicity. The elevated activation levels may be signs of a chronic state or may be phobic responses to the testing situations. A minority of patients failed to show these elevated levels.

Panic attacks in young adolescents.

The lifetime prevalence of interview-determined four-symptom panic attacks in 95 ninth graders was 11.6%. Those with panic attacks were significantly more depressed, were significantly more likely to have separated or divorced parents, and tended to be more likely to have tried cigarette smoking.

Does ischemia occur with panic attacks?

OBJECTIVE: The authors examined ambulatory ECG changes during panic attacks in patients with panic disorder. METHOD: Ten otherwise healthy women with panic disorder and complaints of chest pain during panic attacks underwent a symptom-limited exercise test on a treadmill and then wore an ambulatory ECG monitor with software designed to detect and record ischemic events and used a hand-held computer for up to 6 days. RESULTS: Eight of the women had panic attacks while using the hand-held computer and the ECG monitor. No ischemic events occurred during any of the exercise tests. Twelve tachycardiac events occurred during panic attacks and 84 tachycardiac events occurred that were not associated with panic attacks. Panic attacks were associated with significantly more symptoms than were tachycardiac episodes. CONCLUSIONS: In this group of otherwise healthy women with panic disorder and chest pain, ambulatory ischemic changes were not recorded during panic attacks.

Comparative phenomenology of early-onset versus late-onset panic attacks: a pilot survey.

Studies of panic attacks in older adults are virtually nonexistent. The authors surveyed 520 adults with panic attacks; 445 were younger than age 55, 57 were 55 years old or older but had their first panic attack before age 55, and 18 were 55 years old or older and had their first panic attack at age 55 or later. The respondents with late-onset panic attacks reported fewer symptoms during their attacks and were less avoidant than both groups of respondents with early-onset panic attacks.

Plasma lipid levels in patients with panic disorder or agoraphobia.

Plasma lipids were measured in 102 subjects with panic disorder or agoraphobia. In women, but not men, a significantly higher than expected number of subjects had cholesterol values that exceeded the 75th percentile of national reference values for their sex and age.

Surreptitious drug use by patients in a panic disorder study.

In a double-blind, placebo-controlled trial comparing alprazolam and imipramine for panic disorder, serum analysis revealed that a substantial proportion of the patients took explicitly prohibited anxiolytic medication. Excluding these patients changed the results.