A histone deacetylase inhibitory prodrug - butyroyloxymethyl diethyl phosphate - protects the heart and cardiomyocytes against ischemia injury.

Butyroyloxymethyl diethylphosphate (AN-7) is a prodrug of butyric acid effective in reducing cardiotoxicity caused by chemotherapy. In this study, we tested whether AN-7 protects the heart and cardiomyocytes against ischemia injury. A single oral dose of AN-7 was given to mice or rats. Animals were sacrificed 1.5 or 24 h later and the hearts were subjected to ischemia and reperfusion ex-vivo (Langendorff). The mechanical performance was recorded throughout and the infarct size was measured at the end of reperfusion. Neonatal rat cardiomyocytes were subjected to 24-48 h hypoxia (1% O(2)) in the absence or presence of AN-7 and mitochondria damage and cell death were assessed. Proteins were analyzed by Western immunoblotting. In the two rodents, a single dose of AN-7 given in vivo preconditioned the hearts for improved functional recovery from ischemia and reperfusion performed ex-vivo. Both 1.5 h and 24 h treatments improved the pressure-related parameters whereas the coronary flow was ameliorated in the 24 h treatment only. Infarct size was smaller in the AN-7 treated hearts. In cardiomyocytes, AN-7 diminished the hypoxia induced dissipation of mitochondria membrane potential and cell death. Compared with untreated controls, AN-7-treated hearts recovering from global ischemia and cardiomyocytes undergoing hypoxia, displayed significantly higher levels of the cytoprotective heme oxygenase-1. Our findings indicate that AN-7 imparts cardioprotection against ischemia both in vivo and in vitro and emerges as a potential treatment modality for cardiac injury.

Two cases of Mycobacterium microti derived tuberculosis in HIV-negative immunocompetent patients.

We describe two cases of Mycobacterium microti infection causing pulmonary tuberculosis (TB) in HIV-seronegative immunocompetent patients in Germany. The isolates were identified as M. microti of the llama and vole types, according to spoligotype patterns. Our data demonstrate that M. microti can cause severe pulmonary TB in immunocompetent patients.

A developmental model applied to problems of deafness.

From the Editors: This article represents another in our series of "classics" that helped to shape the field of deaf studies and deaf education. The article first appeared as Chapter Two in Sound and Sign: Childhood Deafness and Mental Health, H. S. Schlesinger and K. P. Meadow (1972), Berkeley: University of California Press. The book reported pioneering research and clinical mental health services at the Langley Porter Neuropsychiatric Institute, University of California, San Francisco. For current readers, some of the language may seem out of date, and the Editors have made several minor modifications to ensure that readers fully recognize the original intention of the author. (Such modifications are indicated by square brackets or ellipses for contemporary purposes, but the intentions of the original all have been maintained, and Editors' notes are indicated as such to distinguish them from the Authors' notes.) Nevertheless, many of the ideas are fresh and important. Indeed, some passages serve as particular reminders of significant changes in opportunities for and attitudes about Deaf people over the past three decades. Many of these changes resulted directly from the work of Dr. Schlesinger and her colleagues.

Does managing behavioral health care services increase the cost of providing medical care?

This study examined the possibility that managing behavioral health care services achieves savings by cost shifting--by denying care or impeding access to care--and in that way encouraging patients to seek needed behavioral health care in the medical care system. In 1993, a large industrial company carved out employee behavioral health care from its unmanaged, indemnity medical care benefits and offered employees an enhanced benefit package through a managed behavioral health care company. This study compared the use and cost of behavioral health care and medical care services for two years before the carve-out and for three years afterward. The rate of behavioral health care usage remained the same or increased after the carve-out, while the cost of providing the care decreased. Controlling for trends that began before the inception of managed behavioral health, medical care costs decreased for those using behavioral health care services. No evidence supporting cost shifting was found.

Adenosine stimulates ANP expression in cultured ventricular cardiomyocytes.

Adenosine protects the ischemic myocardium by coronary vasodilation and the depression of heart rate and contractility, improving myocardial energy balance. Adenosine effects on the myocardium are mediated predominantly by the type A1 receptors. Atrial natriuretic peptide (ANP), a vasodilator and regulator of blood volume, is secreted from either atrial or ventricular myocytes in response to cellular distention. In vivo, adenosine infusion has been shown to induce a rapid increase in plasma ANP, independent of blood pressure. We examined the possibility that adenosine enhances ANP-gene expression in cardiac myocytes. Administration of adenosine (10 microM) to cultured neonatal rat cardiomyocytes led to a 1.7-fold increase (p = 0.014, n = 9) in the abundance of ANP messenger RNA (mRNA) within 30 min, as measured by Northern blot hybridization. No such increase was obtained when adenosine was coadministered with 8-cyclopentyl-1,3dipropylxanthine (CPX, 10 microM), an adenosine A1-receptor antagonist. Our results point at adenosine as regulator of ANP mRNA level in cardiac myocytes.

The myocardial profile of the cytosolic isozymes of creatine kinase is apparently not related to cyanosis in congenital heart disease.

BACKGROUND: CKMB, the cardiac-specific heterodimer of cytosolic creatine-kinase (CK), is developmentally and physiologically regulated, tissue hypoxia being a proposed regulator. In patients with cyanotic heart disease the myocardium is perfused with partially saturated blood. We questioned whether the myocardium of cyanotic subjects contains higher proportions of CKMB. MATERIALS AND METHODS: CK activity, the distribution of cytosolic CK isozymes, activity of lactic dehydrogenase (LDH), and tissue protein content were determined in obstructive tissues removed at corrective surgery of patients with congenital heart defects. Cyanotic (n = 13) and acyanotic (n = 12) subjects were compared. RESULTS: In cyanotic and acyanotic patients, CK activity was 8.4 +/- 0.6 and 7.6 +/- 0.6 IU/mg protein and the proportion of CKMB was 21 +/- 1.4 and 22 +/- 2. 0% (mean +/- S.E.M), respectively. In the two groups of patients, the activity related to the B subunit corresponded to the steady-state level of the CKBmRNA. The tissue content of protein and the activities of CK and LDH were similar in cyanotic and acyanotic subjects and increased with the age. CONCLUSIONS: The lack of difference in CKMB distribution between the cyanotic and acyanotic patients may either indicate that hypooxygenation is not a regulator of CK isozyme expression, or may be attributed to the already high proportion of this isozyme in hypertrophied, obstructive tissues. Recruitment of additional CKMB, in the cyanotic hearts, may thus not be required.

Mental health/medical care cost offsets: opportunities for managed care.

Health services researchers have long observed that outpatient mental health treatment sometimes leads to a reduction in unnecessary or excessive general medical care expenditures. Such reductions, or cost offsets, have been found following mental health treatment of distressed elderly medical inpatients, some patients as they develop major medical illnesses, primary care outpatients with multiple unexplained somatic complaints, and nonelderly adults with alcoholism. In this paper we argue that managed care has an opportunity to capture these medical care cost savings by training utilization managers to make mental health services more accessible to patients whose excessive use of medical care is related to psychological factors. For financial reasons, such policies are most likely to develop within health care plans that integrate the financing and management of mental health and medical/surgical benefits.

Cardiomyocytes in culture--a model to study the cellular actions of amiodarone.

The extensive use of amiodarone as an anti-arrhythmic drug is hampered by numerous side effects and by insufficient knowledge of its cellular action. The use of cell cultures for studying the mechanism of amiodarone action has been questioned, since available information has indicated that the doses employed for the experiments induce cell damage. We have defined conditions to obtain the amiodarone effect on cardiac cells in culture with no detectable damage. Amiodarone, 1 microg/ml, a concentration comparable to serum levels of the drug in acute and chronically treated humans and rats, reduces cell contractions, modifies membrane electrical properties accordingly, increases ATP content, but does not alter cell substructure or change enzyme activities. We strongly support the use of cell cultures for studying the cellular action(s) of amiodarone and offer conditions suitable for such experiments.

The effect of angiotensin II on myosin heavy chain expression in cultured myocardial cells.

Angiotensin II (AII), the principal mediator of the renin-angiotensin system, is an important regulator of vascular and cardiac homeostasis. AII has also been shown to be a regulator of cardiac hypertrophy and of the corresponding changes in amount and composition of certain tissue proteins. We examined the trophic effects of AII on cultured myocytes derived from neonatal rat ventricles and followed, by Northern blot analysis and polyacrylamide gel electrophoresis, the expression of alpha- and beta-myosin heavy chain iso-mRNAs and isoproteins. Our findings show that a single administration of AII is sufficient to induce a trophic response in cultured beating myocytes and to enhance the expression of beta-myosin heavy chain iso-mRNA and isoprotein, having no effect on alpha-myosin heavy chain. Induction of alpha-myosin heavy chain expression by thyroid hormone before AII was administered showed that AII could not potentiate a shift from alpha- to beta-myosin heavy chain predominance. We suggest that the potency of AII to regulate the expression of myosin heavy chain isogenes is restricted to the beta isoform and is overridden by thyroid hormone.

The fear of being left half-cured.

The complaint, "You are leaving me half-cured" is often heard from borderline patients in mid-recovery. They fear they are losing more than they could possibly gain; losing both the familiar sense of self given by their illness and the therapist, who will lose interest and abandon them far short of their fantasized ideal. Although cast in terms of an uncertain future, the phenomenon is to be understood in relation to change that has already occurred and requires working-through its implications both for the patient's external adjustment and in relation to the patient's inner world.

Facts is facts--or is they?

The author argues that to consider the place of facts in psychoanalysis one must first of all distinguish between the use of the term fact in its everyday sense, in which its opposite would be untruth, from the scientific sense in which the term refers to a construction that has been awarded the status of fact by the theory in which it is embedded. Theories in sciences of human behaviour or experience must include not just the hierarchical arrangement of concepts and constructs of the physical sciences, but also the process orientation in which time is the major organising dimension. Facts, as constructs, have different significance in each of these versions of theory, and the meaning of validation, as well as the procedures for determining validity, also differ.

Effects of amiodarone on beating rate and Na-K-ATPase activity in cultured neonatal rat heart myocytes.

1. The purpose of this study was to examine the possibility that the cellular action of amiodarone is mediated by inhibition of thyroid hormone regulatory functions within the myocardial cell. We measured the rate of cell beating and the activity of Na-K-ATPase in cultured neonatal rat heart myocytes. 2. Amiodarone (0.25 and 1 microgram/ml) reduced beating rate up to 75% within 20 min, and Na-K-ATPase activity up to 40% within 2 hr. No toxic effects were detected in the treated cells. 3. The inhibitory actions of amiodarone on beating rate and Na-K-ATPase activity were the same in myocytes grown in the presence or absence of 3-iodothyronine (T3, 5 nM). 4. These data indicate that amiodarone affects beating rate and Na-K-ATPase activity independently of thyroid hormone. It is suggested that interference of amiodarone with thyroid hormone action is not the only mechanism by which this drug modulates some functions of the myocardial cell.

The process of interpretation and the moment of change.

The effectiveness of analytic interpretation is conditioned by a number of factors within the patient, within the analyst, and within the analytic situation. I will focus on one of these factors, part of the technical activity of the analyst that I will call follow-up interpretation, one which omitted, or even slighted, sharply diminishes the effectiveness of interpretation.

Molecular manifestations of cardiac hypertrophy in the spontaneously hypertensive rat effects of antihypertensive treatments.

Antihypertensive treatments were given to young and adult SHRs, to prevent and reverse hypertension, respectively. Cardiac hypertrophy and the steady state level of the "fetal" genes, ANP, alpha-skeletal actin (alpha-skA), and beta myosin heavy chain (beta-MHC) mRNAs were assessed. Our findings show that the reduction of blood pressure does not consistently result in a similar regression of the "fetal gene program".

Women and outpatient mental health services: use by black, Hispanic, and white women in a national insured population.

Factors affecting ethnic differences in women's use of outpatient mental health services were analyzed to determine whether lower use by black and Hispanic women occurred when socioeconomic and other factors are controlled. Employing the Andersen and Newman model of health use, insurance claims of 1.2 million federal employees insured by Blue Cross/Blue Shield in 1983 were analyzed to identify significant predictors of use. Results revealed that black and Hispanic women had lower probabilities and amounts of use when compared to white women even after controlling for a number of variables. Further research is needed to examine cultural and gender-related factors that may underlie ethnic differences; attitudinal factors and service system barriers are also implicated. Such findings have policy implications in the current climate of health care reform for which efforts are needed to increase access to care for ethnic minority women and other underserved populations.

Ethnic differences in use of inpatient mental health services by blacks, whites, and Hispanics in a national insured population.

OBJECTIVE: We examine whether ethnic differences in use of inpatient mental health services exist when the usually confounding effects of minority status and culture are minimized or controlled. DATA SOURCES AND STUDY SETTING: Secondary analyses were conducted using a national insurance claims database for 1.2 million federal employees and their dependents insured by the Blue Cross/Blue Shield (BC/BS) Federal Employees Plan (FEP). STUDY DESIGN: The Andersen-Newman model of health utilization was used to analyze predisposing, enabling, and need variables as predictors of inpatient mental health utilization during 1983. The study design was cross-sectional. DATA COLLECTION: The study database was made up of BC/BS insurance claims, Office of Personnel Management employee data, and Area Resource File data. PRINCIPAL FINDINGS: No significant differences were found among blacks, whites, and Hispanics in the probability of a psychiatric hospitalization or in the number of inpatient psychiatric days. Regression analyses revealed younger age and psychiatric treatment of other family members as significant predictors of a hospitalization; region of residence, younger age, hospital bed availability, and high option plan enrollment were significant predictors of the number of treatment days. CONCLUSIONS: Ethnic differences in use of inpatient mental health services were not significant in this generously insured population. Further research involving primary data collection among large and diverse samples of ethnic individuals is needed to fully examine the effects of cultural and socioeconomic differences on use of mental health services.

How the analyst listens: the pre-stages of interpretation.

There has been little systematic treatment of the pre-stages of interpretation that include the process of analytic listening itself, and the gathering and sorting of information that could lead to the formulation of an interpretation. The situation of the analyst as listener is compared with that of the social listener, and the focus is on processes close to the surface of experience. Three 'modes' of listening are described that must be continuously available to the analyst, and which taken together capture the sense of 'evenly hovering attention'. The use and misuse of the concept of empathy in relation to analytic listening are discussed.

Ethnicity and the use of outpatient mental health services in a national insured population.

OBJECTIVES: Factors affecting ethnic differences in the use of outpatient mental health services are analyzed in an insured, nonpoor population to determine if lower use by Blacks and Hispanics persists when socioeconomic and other factors are controlled. METHODS: To identify significant predictors of the probability and amount of use, insurance claims data for a population of 1.2 million federal employees insured by Blue Cross/Blue Shield in 1983 were analyzed with the Andersen and Newman model of health service utilization. Logistic and ordinary least squares regression models were estimated for each ethnic group. RESULTS: Blacks and Hispanics had lower probabilities and amounts of use when compared with Whites after controlling for a number of variables. CONCLUSIONS: Since ethnic differences in the use of outpatient mental health services exist even in an insured, nonpoor population, factors other than lower socioeconomic status or insurance coverage--for example, cultural or attitudinal factors and service system barriers--are likely responsible. Such findings have policy implications in the current climate of health care reform to increase access to care for the underserved.