Cerebral Microvascular Density, Permeability of the Blood-Brain Barrier, and Neuroinflammatory Responses Indicate Early Aging Characteristics in a Marfan Syndrome Mouse Model.

Marfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 ( Fbn1 ), where a Fbn1 missense mutation ( Fbn1 C1039G/+ ) can result in systemic increases in the bioavailability and signaling of transforming growth factor-ß (TGF-ß). In a well-established mouse model of MFS ( Fbn1 C1041G/+ ), pre-mature aging of the aortic wall and the progression of aortic root aneurysm are observed by 6-months-of-age. TGF-ß signaling has been implicated in cerebrovascular dysfunction, loss of blood-brain barrier (BBB) integrity, and age-related neuroinflammation. We have reported that pre-mature vascular aging in MFS mice could extend to cerebrovasculature, where peak blood flow velocity in the posterior cerebral artery (PCA) of 6-month-old (6M) MFS mice was reduced, similarly to 12-month-old (12M) control mice. Case studies of MFS patients have documented neurovascular manifestations, including intracranial aneurysms, stroke, arterial tortuosity, as well as headaches and migraines, with reported incidence of pain and chronic fatigue. Despite these significant clinical observations, investigation into cerebrovascular dysfunction and neuropathology in MFS remains limited. Using 6M-control ( C57BL/6 ) and 6M-MFS ( Fbn1 C1041G/+ ) and healthy 12M-control male and female mice, we test the hypothesis that abnormal Fbn1 protein expression is associated with altered cerebral microvascular density, BBB permeability, and neuroinflammation in the PCA-perfused hippocampus, all indicative of a pre-mature aging brain phenotype. Using Glut1 staining, 6M-MFS mice and 12M-CTRL similarly present decreased microvascular density in the dentate gyrus (DG), cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) regions of the hippocampus. 6M-MFS mice exhibit increased BBB permeability in the DG, CA1, and CA3 as evident by Immunoglobulin G (IgG) staining, which was more comparable to 12M-CTRL mice. 6M-MFS mice show a higher number of microglia in the hippocampus compared to age-matched control mice, a pattern resembling that of 12M-CTRL mice. This study represents the first known investigation into neuropathology in a mouse model of MFS and indicates that the pathophysiology underlying MFS leads to a systemic pre-mature aging phenotype. This study is crucial for identifying and understanding MFS-associated neurovascular and neurological abnormalities, underscoring the need for research aimed at improving the quality of life and managing pre-mature aging symptoms in MFS and related connective tissue disorders.

A mechanism for improved talc pleurodesis via foam delivery.

Talcum powder is recognized as the leading drug for pleurodesis, a treatment of choice for malignant pleural effusions. Recently, it was shown that hydrogel foam delivery systems significantly enhanced the number of adhesions between the chest wall and the lung in a New Zealand rabbit model due to the sol-gel transition. However, many questions still remain regarding the cause of improved efficacy, such as: (1) Would only hydrogel foams improve the efficacy of talc pleurodesis? (2) Is it possible to achieve the same efficacy of hydrogels using non-hydrogel foams? 3) What are the physicochemical properties that can be correlated to the efficacy of talc pleurodesis? In this study, we use non-hydrogel foam formulations to determine the efficacy of pleurodesis. Foam stability and rheology of the formulations were correlated to adhesion formation. The results clearly suggest a correlation of pleurodesis efficacy to the viscosity and modulus of the foam delivery system.

Complete recovery after massive ethylene glycol ingestion.

We treated a 64-year-old man who recovered completely from a massive antifreeze ingestion with ethylene glycol levels well above those of previously described survivors. Rapid and aggressive treatment of the patient with recognized methods, including hemodialysis, resulted in the favorable outcome.

CDC growth charts: United States.

OBJECTIVES: This report presents the revised growth charts for the United States. It summarizes the history of the 1977 National Center for Health Statistics (NCHS) growth charts, reasons for the revision, data sources and statistical procedures used, and major features of the revised charts. METHODS: Data from five national health examination surveys collected from 1963 to 1994 and five supplementary data sources were combined to establish an analytic growth chart data set. A variety of statistical procedures were used to produce smoothed percentile curves for infants (from birth to 36 months) and older children (from 2 to 20 years), using a two-stage approach. Initial curve smoothing for selected major percentiles was accomplished with various parametric and nonparametric procedures. In the second stage, a normalization procedure was used to generate z-scores that closely match the smoothed percentile curves. RESULTS: The 14 NCHS growth charts were revised and new body mass index-for-age (BMI-for-age) charts were created for boys and girls (http://www.cdc.gov/growthcharts). The growth percentile curves for infants and children are based primarily on national survey data. Use of national data ensures a smooth transition from the charts for infants to those for older children. These data better represent the racial/ethnic diversity and the size and growth patterns of combined breast- and formula-fed infants in the United States. New features include addition of the 3rd and 97th percentiles for all charts and extension of all charts for children and adolescents to age 20 years. CONCLUSION: Created with improved data and statistical curve smoothing procedures, the United States growth charts represent an enhanced instrument to evaluate the size and growth of infants and children.

Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP.

Elevated plasma atrial natriuretic peptide (ANP) levels have been shown to blunt pulmonary hemodynamic responses to chronic hypoxia, but whether elevated circulating ANP levels negatively feedback on cardiac expression of the ANP gene is unknown. Using a recently developed strain of transgenic mouse (TTR-ANF) that expresses a transthyretin promoter-ANP fusion gene in the liver, we studied the effect of chronically elevated plasma ANP levels on cardiac hypertrophic and pulmonary hemodynamic responses and expression of the endogenous cardiac ANP gene during chronic hypoxia. Plasma ANP levels were 10-fold higher in TTR-ANF mice than in their non-transgenic littermates. After 3 wk of hypobaric hypoxia (0.5 atm), right ventricular hypertrophy and pulmonary hypertension had developed in both groups of mice, but TTR-ANF mice had lower right ventricle-to-left ventricle plus septum weight ratios (0.39 +/- 0.01 vs. 0.45 +/- 0.02), right ventricular systolic pressures (25 +/- 2 vs. 29 +/- 2 mmHg), and lung dry weight-to-body weight ratios (0.48 +/- 0.03 vs. 0.57 +/- 0.01 mg/g) and less muscularization of peripheral pulmonary vessels (8.3 +/- 1.4 vs. 17.4 +/- 2.5%) than nontransgenic controls. Right atrial and ventricular steady-state ANP mRNA levels were the same in both groups of mice under normoxic and hypoxic conditions despite much higher plasma ANP levels and less pulmonary hypertension in TTR-ANF mice. We conclude that chronically elevated plasma ANP levels attenuate the development of hypoxic pulmonary hypertension in mice but do not suppress cardiac expression of the endogenous ANP gene under normoxic conditions nor blunt the upregulation of right ventricular ANP expression during chronic hypoxia.

Comparison of extended versus brief treatments for marijuana use.

Adult marijuana users (N = 291) seeking treatment were randomly assigned to an extended 14-session cognitive-behavioral group treatment (relapse prevention support group; RPSG), a brief 2-session individual treatment using motivational interviewing (individualized assessment and intervention; IAI), or a 4-month delayed treatment control (DTC) condition. Results indicated that marijuana use, dependence symptoms, and negative consequences were reduced significantly in relation to pretreatment levels at 1-, 4-, 7-, 13-, and 16-month follow-ups. Participants in the RPSG and IAI treatments showed significantly and substantially greater improvement than DTC participants at the 4-month follow-up. There were no significant differences between RPSG and IAI outcomes at any follow-up. The relative efficacy of brief versus extended interventions for chronic marijuana-using adults is discussed.

Relapse prevention as an interventive model for HIV risk reduction in gay and bisexual men.

Despite considerable self-initiated HIV risk reduction among men who have sex with men, little is known about how to design interventions that will effectively assist individuals from this population in maintaining safer sex behaviors over time. The present study evaluated the effectiveness of a 17-session group counseling intervention that incorporated components based on a cognitive-behavioral model of relapse. Differential behavioral outcomes following treatment included an increase in the percentage of sexual activities that were protected and a decrease in unprotected oral sex. However, considerable risk reduction (e.g., increased condom use, decreased unprotected sex, and decreases in the number of male partners and in the total number of sexual acts) occurred in both treated and untreated participants. Measures of mediating attitudinal variables drawn from relapse prevention theory largely predicted behavioral changes. Over time, several of the risk reduction behaviors achieved at posttreatment were not maintained, suggesting the importance of further developing effective strategies for supporting behavior change maintenance.

Determinants of attrition from cessation treatment in smokers with a history of major depressive disorder.

Attrition from smoking cessation treatment by individuals with a history of major depression was investigated. An investigation of preinclusion attrition examined differences between eligible smokers who did (n = 258) and did not (n = 100) attend an initial assessment session. Postinclusion attrition was investigated by comparing early dropouts (n = 33), late dropouts (n = 27), and treatment completers (n = 117). Those who failed to attend the assessment session were more likely to be female, to smoke cigarettes with higher nicotine content, and to have a history of psychotropic medication use. Early-treatment dropouts reported a higher smoking rate than late-treatment dropouts and endorsed more symptoms of depression than late dropouts and treatment completers. Results are compared with previous investigations of smoking cessation attrition, and implications for treatment and attrition prevention are discussed.

Perception of male drinkers as a function of their alcoholic beverage preference.

The present study examined perception of a man's likelihood of driving after drinking and his ability to do so as a function of his choice of beverage. Perceptions of his social characteristics were also examined. The sample was composed of 200 volunteer undergraduate psychology students. Equal numbers of male and female subjects read one of four vignettes which varied only in the male protagonist's choice of beverage: beer, wine, shots of distilled spirits, or cola. After reading the story, subjects answered multiple-choice questions about the character, tapping social judgments, situational judgments and drinking and driving judgments. Subject drinking habits were also assessed. The most notable result was the consistently positive perception of the protagonist portrayed as an abstainer. The lack of a consistent alcoholic beverage distinction implies that the beer-spirits double standard is far from a clear-cut discrimination. Possible explanations for results are discussed. This study questions the robustness of the alcoholic beverage type bias and reflects the need for future research.

Person perception as a function of drinking behavior, gender and sex role stereotypes.

Gender and the level of drinking of the protagonist in a vignette were systematically varied to examine the effects of these variables on the inferences 400 undergraduates drew about the personal attributes and future of the character. Results showed that gender of the target did not significantly affect judgments about the protagonist, but perceptions of the character were strongly influenced by the alcohol-related behaviors attributed to him or her in the vignette. Evaluations of the protagonist generally became less favorable as drinking level increased. Abstainers were also viewed more positively than at least some comparison groups of drinkers on most measures. Although heavier drinkers were often stigmatized, they were also seen as having more fun. Subject gender, sex role attributes and attitudes toward women failed to influence judgments about the protagonists, but raters' own drinking habits did have an impact. Heavier drinkers showed a tendency to rate heavier drinking protagonists more favorably than did lighter drinkers. Implications of these results for prevailing theories about norms and evaluations affecting drinkers are discussed.

Testing the abstinence violation effect construct with marijuana cessation.

It has been proposed that internal, stable, and global attributions for the cause of a lapse following a period of abstinence and concomitant feelings of guilt and loss of control increased the probability of a return to regular substance use. The Abstinence Violation Effect (AVE) hypotheses were tested in a sample of 75 adult marijuana users who reported a lapse into marijuana use following completion of either a relapse prevention (RP) or social support group treatment aimed at abstinence. Results showed that more internal, stable, and global attributions for the cause of the lapse and perceived loss of control were related significantly to concurrently reported relapse. Further, internal and global attributions predicted marijuana use during the subsequent 6 months. Results are discussed in terms of support for the AVE construct, treatment implications, and the failure of the RP treatment to modify reactions to a lapse.

Evaluation of a cognitive-behavioral therapy intervention to improve body image and decrease dieting in college women.

This two-group experimental study evaluated the effectiveness of a cognitive-behavioral body image intervention, adapted from an effective clinical intervention, with normal college females. Participants included nonclinical, freshman college women who were assigned randomly to either the experimental intervention or the control group (brief educational session). Participants were assessed prior to the intervention and again 1 month later on dieting behavior, body image, fear of fat, and anxiety concerning physical appearance. Although it was hypothesized that each of these variables would be lower in the experimental group, none of these results, except for a trend for decreased dieting, were found. Overall these results of slightly reduced dieting behavior are consistent with other research targeting primary and secondary prevention. This intervention's failure to impact body image and eating behaviors of college students illustrates the continuing challenge of eating disorders prevention.

Psychological, nutritional, and energy expenditure differences in college females with anorexia nervosa vs. comparable-mass controls.

This is the first study to examine psychological and behavioral variables in nonhospitalized college females with subclinical anorexia nervosa (AN) as compared to healthy college females of comparable body mass (i.e., body mass index (BMI)<19). Participants who met all DSM-IV [Diagnostic and statistical manual of mental disorders, 4th ed. (1994). Washington, DC: APA.] criteria for AN-restrictive type (except for BMI<17.5; n=11) and control participants (n=15) with comparable body mass completed psychological, nutritional, and exercise assessments. Results suggested that those with AN evidenced more general psychopathology, more eating disorder symptoms, more dieting, more compulsive exercise, and less consumption of calories compared to participants in the control group. There was no difference in macronutrient consumption. There was no significant difference in expenditure of energy, despite differences in reports of compulsive exercise. Given similar body mass, this suggests that the women with AN were experiencing an energy deficit consistent with the disorder's defining features of "fear of gaining weight or becoming fat" and provides us with more understanding of individuals with AN in their natural environment.

On being a person of integrity ... or ethics and other liabilities.

The emergence of managed care and the health industry's response to it has precipitated a moral crisis for many health care professionals. Caught between the patients' best interests and the employers' and payers' restrictions, professionals find their good intentions tested. In this article, the author distinguishes moral from ethical problems and suggests that self-examination and self-diagnosis of the mindsets and conditions that contribute to moral malfunctioning in the workplace--self-management at the individual level--is essential for maintaining the ethical stance of the profession and the integrity of the professional.

25 years: a slightly irreverent retrospective.

From 1970 when room rates soared to 50 dollars a day, to the reorganization occasioned by DRGs, and restructuring for healthcare reform in the 1990s; from the gleaming white supervisory nurse of yesteryear, through nursing's image crisis, to the vice presidents and case managers of today; from the rise of critical care units to the development of ethics committees, Nursing Management's editor chronicles and comments on the major (and sometimes minor) events of the last 25 years of nursing.

The ethics of managed care: Part 3--Toward a common vision.

A common set of values is one of the primary unifying elements of any systematized group. The moral crisis in health care today has more to do with value dis-integration than economic dis-array. The use of resource allocation mechanisms like managed care expand the needs of conscience with those of man-willed choice. If health professionals are to meet the ethical challenges of "managed care," they must start by reminding themselves of what the scientific and ethical commitments both promise and imply.

Health reform: the shape of things to come.

To understand the various legislative initiatives at state and national levels, one must know what questions to ask and what issues are raised by each question. The questions are: (1) How much shall we reform the system? (2) How quickly shall we reform the system? (3) How shall we fund the system? and (4) How shall we organize or reorganize the system? If the complex issues these questions raise are dealt with quickly, boldly and fairly, meaningful health reform will be passed in 1993 and phased in over the next five to seven years.

Abortion: a tangle of rights.

PIP: Management of abortion personnel within a hospital setting involves a number of rights: the patient's rights to privacy and to the provision of competent, compassionate, and understanding nursing care; the right of nurses to refrain from abortion procedures due to conscience; and the right of hospitals to hire employees who will fulfill their contractual obligations. The US Supreme Court has held that the decision to abort is protected under the right to privacy; no one may interfere with a woman's decision. Public institutions do not have an obligation to fund abortion. If the Court had made abortion a right, then society would be obliged to provide abortion. The discussion of abortion rights focuses on the following topics: the legal duties of health professionals, the legal and moral rights and obligations of nurses, the legal rights and obligations of hospitals, and the rights of abortion patients. A case study is provided of a head nurse and staff in the gynecology ward of a large metropolitan hospital in 1974 who objected to the performance of saline abortion on the ward, to disposing of the fetuses, and to the validity of patients' consent. Their concern was for the health and safety of patients and the rights of patients to informed consent. The hospital did not have a right to force the nurses to comply with the directive on saline abortion procedures, because the hospital did not have the right to violate the conscience of an individual citizen. In another example of a transfer of a nurse to another area of the hospital, the hospital was exercising its prerogative to expect fulfillment of contractual obligations in a way that did not interfere with health care workers' objections to abortion. Roe v. Wade and Doe v. Bolton were the 2 cases that established the existence of institutional conscience. Health care workers have an obligation to inform hospitals in writing if they have objections to participation in abortion procedures. Nurses have an obligation to respect the legal right to privacy in making or carrying out an abortion decision, and to provide competent nursing care to all who receive their services. Nurses should not make judgments about their approval or disapproval of abortion or the patient's reasons for abortion. Patients have a right to be protected from emotional and physical harm from objecting nurses; nurses may withdraw their services only if there are other qualified professionals available to provide care.^ieng

Abortion: the limits of moral repugnance.

PIP: Elective abortions in hospitals after 26 weeks may lead to retaliation by nursing staff and others morally opposed. Policy has stipulated that agencies established for the purpose of performing abortions need not hire health personnel opposed to abortion. Private institutions and religiously affiliated institutions need not perform abortions. Public hospitals have policies that stipulate 1) the time frame for abortions; 2) the justifiable reasons for abortion; 3) conditions or exceptions; 4) procedures for health personnel applying conscientious objection to abortion; 5) the limits of refusal for conscientious objectors; 6) procedures for disposal of the aborted fetus; 7) procedures for fetal research; and 8) procedures in the event of an unexpected live birth. Conscientious objectors to abortion have been unjustifiably accused of making moral judgments about the patient or imposing their morality on others. Policy should respect the moral decision of patients and providers. Accepting another's moral position has requirements of accommodation and not agreement. The worst kind of hypocrisy has involved health personnel invoking conscientious objection and then engaging in morally repugnant behavior in harassing patients. Morally imposing one's views on others violated patients' right to privacy and became an action in violation of licensing permits. Hospitals must discipline or discharge health personnel who violate a breach of medical ethics. An active ethics committee should educate personnel.^ieng