Risk factors for postpartum depressive symptoms in low-income women with very low-birth-weight infants.

PURPOSE: This study examined factors associated with postpartum depressive symptoms in mothers with premature infants in the neonatal intensive care unit (NICU). SUBJECTS: A total of 113 new mothers with very low-birth-weight infants in their initial NICU admission were recruited from 2 urban hospitals servicing low-income minority communities. DESIGN: This study employed a cross-sectional design. METHODS: Data were collected during the infants' postpartum NICU admission and included maternal demographic information (eg, age, education, race, living with the baby's father), infant illness severity (Neurobiologic Risk Score from infant's medical record), and maternal psychological measures (the Center for Epidemiologic Studies Depression Scale, the Perinatal Posttraumatic Stress Questionnaire, and the State-Trait Anxiety Inventory). RESULTS: The findings indicated that 47 (42%) women had elevated postpartum depressive symptoms and 33 (30%) women had elevated postpartum posttraumatic stress symptoms (PTSs). Factors associated with postpartum depressive symptoms included PTS, anxiety, maternal age, and whether the mother lived with the baby's father (F4, 104 = 52.27, P < .001). The severity of the infants' illness, parental stress, and maternal education were not associated with depressive symptoms among low-income mothers of NICU infants. CONCLUSIONS: On the basis of our findings, we recommend that low-income women should be screened for symptoms of anxiety, posttraumatic stress, and postpartum depression on their infants' admission to the NICU. When this is not feasible, we advise NICU healthcare providers to assess women for familial support, maternal age, posttraumatic stress related to their infants birth, and anxiety to determine which mothers are at the greatest risk for postpartum depressive symptoms. Screening for postpartum depression in the NICU can aid in early identification and treatment, thereby decreasing negative consequences for mothers and their infants.

Depressive symptoms in the second trimester relate to low oxytocin levels in African-American women: a pilot study.

Low-income African-American women report elevated prenatal depressive symptoms more often (42 %) than the national average (20 %). In the USA in 2012, 16.5 % of African-American women experienced a premature birth (less than 36 completed gestational weeks) compared to 10.3 % of white women. In addition, 13 % of African-American women had a low-birth weight infant (less than 2,500 g) compared to 7 % of white women. Variation in the neuropeptide, oxytocin has been implicated in perinatal depression, maternal behavior, regulation of stress responses, and may be associated with this health disparity. The purpose of this investigation was to examine factors associated with prenatal depressive symptoms, including plasma oxytocin levels and birth weight, in a sample of urban African-American women. Pregnant African-American women (N = 57) completed surveys and had blood drawn twice during pregnancy at 15-22 weeks and 25-37 weeks. In addition, birth data were collected from medical records. A large number of participants reported elevated prenatal depressive symptoms at the first (n = 20, 35 %) and the second (n = 19, 33 %) data points. Depressive symptoms were higher in multigravidas (t(51) = -2.374, p = 0.02), women with higher anxiety (r(47) = 0.71, p = 0.001), women who delivered their infants at an earlier gestational age (r(51) = -0.285, p = 0.04), and those without the support of the infant's father (F(4, 48) = 2.676, p = 0.04). Depressive symptoms were also higher in women with low oxytocin levels than in women with high oxytocin levels (F(2, 47) = 3.3, p = 0.05). In addition, women who had low oxytocin tended to have infants with lower birth weights (F(2, 47) = 2.9, p = 0.06). Neither prenatal depressive symptoms nor prenatal oxytocin levels were associated with premature birth. Pregnant multigravida African-American women with increased levels of anxiety and lacking the baby's father's support during the pregnancy are at higher risk for prenatal depressive symptoms. Prenatal depressive symptoms are associated with low oxytocin levels and lower infant birth weights. Further research is needed to understand the mechanisms between prenatal depressive symptoms, oxytocin, and birth weight in order to better understand this health disparity.

Gender differences in acculturation, stress, and salivary cortisol response among former Soviet immigrants.

Post-immigration adaptation is characterized by chronic and acute acculturative stressors. Salivary cortisol is a commonly used hormonal marker of stress, but few studies have investigated its use as an indicator of acculturative stress and adjustment in immigrants. The purpose of this study was to examine relationships among predictors of adjustment (environmental and language mastery), self-reported stress outcomes (depressive symptoms, perceived stress, alienation), and salivary cortisol response in immigrants from the former Soviet Union. The sample included 137 married men and women aged 42-80 who lived in the U.S. for 1-13 years. Results indicated that while men and women had similar values for cortisol response, relationships among adjustment measures, stress outcomes, and cortisol differed by gender. Among men, environmental mastery significantly reduced depressive symptoms, perceived stress, and cortisol response. Among women, environmental mastery also reduced depressive symptoms, perceived stress, and alienation, but language mastery increased cortisol response and decreased alienation.

Maternal and umbilical artery cortisol at birth: relationships with epidural analgesia and newborn alertness.

BACKGROUND: Newborn alertness soon after birth facilitates mother-infant interaction and may be related to umbilical cortisol levels. Yet, little is known about whether epidural analgesia influences umbilical cortisol at birth. AIM: The aims of this study were to explore relationships between exposure to epidural analgesia and maternal and umbilical cortisol; maternal and umbilical cortisol levels at birth; and umbilical cortisol and infant alertness after birth. METHOD: Forty women were self-selected to unmedicated or epidural labors in this pilot study. Maternal saliva and infant umbilical artery (UA) plasma at birth were enzyme immunoassayed for cortisol. Infant alertness was assessed nearly 1 hr after birth. RESULTS: Maternal cortisol was higher in the unmedicated versus epidural group (p = .003). Umbilical cortisol was not related to epidural analgesia exposure but was related to duration of labor (higher cortisol with longer labors; p = .026). Maternal cortisol level explained 55% of the variance in umbilical cortisol in the unmedicated group (p = .002), but there was no significant shared variance in the epidural sample (p = .776). There was a positive correlation (r(2) = .17, p = .008) between umbilical cortisol and infant alertness. Latina infants demonstrated a higher frequency of alertness than Black infants. In multivariate analysis, umbilical cortisol (p = .049) and race/ethnicity (p = .024) remained significant predictors of infant alertness. CONCLUSIONS: Our findings indicate that higher umbilical cortisol is related to greater infant alertness soon after birth. While epidural analgesia did not directly relate to infant cortisol, other factors contributed to higher umbilical cortisol.

Signaling responses after exposure to 5 alpha-dihydrotestosterone or 17 beta-estradiol in norepinephrine-induced hypertrophy of neonatal rat ventricular myocytes.

Androgens appear to enhance, whereas estrogens mitigate, cardiac hypertrophy. However, signaling pathways in cells for short (3 min) and longer term (48 h) treatment with 17beta-estradiol (E2) or 5 alpha-dihydrotestosterone (DHT) are understudied. We compared the effect of adrenergic stimulation by norepinephrine (NE; 1 microM) alone or in combination with DHT (10 nM) or E2 (10 nM) treatment in neonatal rat ventricular myocytes (NRVMs) by cell area, protein synthesis, sarcomeric structure, gene expression, phosphorylation of extracellular signal-regulated (ERK), and focal adhesion kinases (FAK), and phospho-FAK nuclear localization. NE alone elicited the expected hypertrophy and strong sarcomeric organization, and DHT alone gave a similar but more modest response, whereas E2 did not alter cell size. Effects of NE dominated when used with either E2 or DHT with all combinations. Both sex hormones alone rapidly activated FAK but not ERK. Long-term or brief exposure to E2 attenuated NE-induced FAK phosphorylation, whereas DHT had no effect. Neither hormone altered NE-elicited ERK activation. Longer term exposure to E2 alone reduced FAK phosphorylation and reduced nuclear phospho-FAK, whereas its elevation was seen in the presence of NE with both sex hormones. The mitigating effects of E2 on the NE-elicited increase in cell size and the hypertrophic effect of DHT in NRVMs are in accordance with results observed in whole animal models. This is the first report of rapid, nongenomic sex hormone signaling via FAK activation and altered FAK trafficking to the nucleus in heart cells.

Detection of salivary oxytocin levels in lactating women.

Oxytocin is a neuropeptide with widespread influence on many physiological and social functions including: labor and birth, lactation, sexual behavior, nurturing maternal behaviors, and stress reduction. However, our understanding of oxytocin's roles has been hampered by lack of noninvasive methods for assessing oxytocin levels. The goal of the present study was to assess whether oxytocin could be detected in saliva and whether changes occurred in the pattern of oxytocin release among lactating women from before, at initiation and after breast feeding. Using a prospective repeated measures design, 11 research participants each provided 18 saliva samples during three feeding cycles (before, at initiation and after breast feeding) for two 24-hr data collection periods (Days 1 and 2). Within each day, saliva was collected at late evening, early morning, and late morning. Salivary samples were concentrated fourfold by dehydration prior to analysis and oxytocin was measured in saliva using an enzyme immunoassay (EIA). Salivary oxytocin values, when reconverted to their original levels, ranged from 6.44 to 61.05 pg/ml. Oxytocin values in saliva varied significantly as a function of the breast feeding cycle, but did not show reliable differences as a function of the time of feeding. Oxytocin was highest before feeding, followed by a decrease at initiation of feeding, and an increase at 30 min after feeding. The findings suggest that oxytocin release into saliva increases in anticipation of feedings. This study also supports the potential usefulness of salivary measures of oxytocin as a noninvasive index of changes in this peptide.

Salivary cortisol and behavioral state responses of healthy newborn infants to tactile-only and multisensory interventions.

OBJECTIVE: To compare changes in stress reactivity (measured via the biomarker salivary cortisol) and behavioral state in healthy newborn infants immediately following 1 of 2 interventions: (1) tactile-only stimulation or (2) a multisensory, auditory, tactile, visual, and vestibular stimulation with a control group. DESIGN: A randomized prospective design pilot study. SETTING: Normal newborn nurseries of 2 midwestern perinatal centers. PARTICIPANTS: Forty healthy newborn infants receiving standard nursing care. METHODS: Infants were randomly assigned to receive 15 minutes of tactile-only, auditory, tactile, visual, and vestibular, or no stimulation 30 minutes before feeding. Saliva samples were collected before, immediately following, and 10 minutes postintervention. Behavioral state was judged every minute. RESULTS: Tactile-only group infants had the largest increase in cortisol levels, followed by control group infants. In contrast, infants who received the multisensory intervention showed a significant steady decline in cortisol. Asleep was the predominant state for all 3 groups and cry was minimal. CONCLUSIONS: Tactile-only stimulation may increase infant stress reactivity while the benefit of the multisensory auditory, tactile, visual, and vestibular intervention may be in the reduction of infant stress reactivity. Interventions appeared to have minimal effect on stress reactivity based on behavioral state.

An exploratory study of neurohormonal responses of healthy men to massage.

OBJECTIVE: This research examined the relationship between plasma oxytocin (OT), arginine vasopressin (AVP), cortisol, and anxiety before, during, and after a massage in healthy adult men. DESIGN: A randomized, controlled, crossover, repeated-measures, prospective experimental design with subjects acting as their own controls was used. SETTING: The research was conducted at a Midwestern University. SUBJECTS: Fourteen (14) healthy men between the ages of 19 and 45 years of age were randomly assigned to the order of two conditions: a 20-minute massage (experimental condition) or a 20-minute reading period (control condition). METHODS: Blood samples were collected at time intervals during each data collection session. Plasma OT, AVP, and cortisol levels were evaluated by enzyme immunoassay (EIA). The Spielberger State Anxiety Inventory (SAI) and autonomic measures were recorded pre- and postcondition. RESULTS: Both experimental (massage) and control (reading) conditions elicited a significant increase in plasma OT levels (p < 0.05) and a decrease in SAI score (p < 0.05) from pre- to postintervention. A significant positive correlation was detected between plasma AVP and plasma cortisol (r = 0.63, n = 24, p = 0.001) in the massage group, whereas a significant positive correlation between plasma AVP and the SAI (r = 0.47, n = 25, p = 0.016) was observed in the reading group. No significant differences were observed for the autonomic measures between conditions. CONCLUSIONS: The finding that plasma OT levels increased in both the massage and reading groups, suggests that tactile stimulus is not necessary for OT release. The results suggest that another unknown factor associated with reduction of anxiety may be involved.

High-dose statin therapy for secondary prevention of stroke: stroke prevention by aggressive reduction in cholesterol levels study review.

It has been shown that HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (statins) lower the incidence of a first stroke in patients with coronary heart disease, diabetes, or risk factors for cardiovascular disease. However, it is unknown whether statin therapy could reduce the incidence of a second stroke in patients without evidence of heart disease. This article reviews the results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial, a prospective, randomized, multicentered, double-blind, placebo-controlled, international trial designed to examine the effect of high-dose atorvastatin on secondary stroke prevention. Trial participants (4,731) had experienced a stroke or transient ischemic attack within 1 to 6 months before randomization into the study. Over the 5-year follow-up period, incidence of second stroke or transient ischemic attack was significantly reduced in the atorvastatin treatment group compared with the placebo group. In addition, high-dose atorvastatin therapy significantly decreased major coronary artery and other negative cardiovascular events. The reduction in incidence of secondary stroke was specific to ischemic stroke as opposed to hemorrhagic stroke. Results of the trial are clinically significant and support extension of the latest secondary stroke prevention guidelines to include statin therapy for those patients without coronary heart disease.

Cardiovascular risk factors and metabolic syndrome in alcohol- and nicotine-dependent men and women.

BACKGROUND AND RESEARCH OBJECTIVE: Cardiovascular disease (CVD) is a leading cause of mortality among alcohol-dependent people; however, minimal data exist on the CVD risk factor profile in this high-risk population. The purpose of this study was to examine the prevalence and clustering of traditional and novel CVD risk factors, including components of the metabolic syndrome, in nicotine- and alcohol-dependent adults. SUBJECTS AND METHODS: Participants (n = 46; 61% men; 87% white), who were a consecutive series of eligible adults (19-56 years of age; mean, 34.8 +/- 1.4 years; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-classified alcoholic; abstinent for or=25 kg/m2); 61% were physically inactive (<1,000 kcal/wk); and 61% had some form of hypertension. In addition, 54% had increased homocysteine values; high-sensitivity C-reactive protein was elevated in 28%; and 22% of the participants met criteria for metabolic syndrome. In this study of the CVD risk profile among alcoholics, subjects were found to have an average of 3 CVD risk factors in addition to cigarette smoking. This prevalence and clustering of potentially modifiable risk factors in young, nicotine-dependent alcoholics indicate the need for aggressive risk reduction focused on prevention of CVD.

Long-term effects of alcohol consumption in male and female rats.

Discrepancies exist regarding potential sex differences in the effects of ethanol on the myocardium. Therefore, the aims of this study were to determine if long-term ethanol consumption was associated with the development of a dilated cardiomyopathy (CM) in female rats and, second, to determine if the absence of ovarian hormones modulated this effect. Adult male and female (n=6-8/group) sham-operated and ovariectomized (OVX) Sprague-Dawley rats received the Lieber DeCarli ethanol-containing (8% vol/vol) or control liquid diet for 8 months. All ethanol groups showed echocardiographic evidence of a cardiomyopathy; however, more significant ethanol-elicited differences were found in the male ethanol group than in either the female or female OVX groups. In addition, the male ethanol group had significant reductions in in vivo measures of contractility, such as the maximum derivative of change in systolic pressure and preload recruitable stroke work. Sex differences were also apparent in the pattern and degree of posterior and septal wall thickness changes, in that the male ethanol group had more posterior and septal wall thinning. In conclusion, similar to male rats long-term ethanol consumption in gonad-intact and OVX female rats is associated with the development of a dilated cardiomyopathy.

Oxytocin: behavioral associations and potential as a salivary biomarker.

Oxytocin (OT) is a neuropeptide that is produced primarily in the hypothalamus and is best known for its role in mammalian birth and lactation. Recent evidence also implicates OT in social behaviors, including parental behavior, the formation of social bonds, and the management of stressful experiences. OT is reactive to stressors, and plays a role in the regulation of both the central and autonomic nervous system, including effects on immune and cardiovascular function. Knowledge of patterns of OT release would be of value in many fields of science and medicine. However, measurements of OT concentration in blood are infrequently performed, and previous attempts to measure OT in saliva have been unsuccessful. Using a sensitive enzyme immunoassay (EIA) and concentrated samples we were able to detect reproducible changes in salivary OT as a function of lactation and massage. These results indicate that measurements of biologically relevant changes in salivary OT are possible. These results confirm the biological relevance of changes in salivary OT with stressors and support saliva as a noninvasive source to monitor central neuroendocrine function.

Detection of cardiac variability in the isolated rat heart.

Cardiac variability can be assessed from two perspectives: beat-to-beat performance and continuous performance during the cardiac cycle. Linear analysis techniques assess cardiac variability by measuring the physical attributes of a signal, whereas nonlinear techniques evaluate signal dynamics. This study sought to determine if recurrence quantification analysis (RQA), a nonlinear technique, could detect pharmacologically induced autonomic changes in the continuous left ventricular pressure (LVP) and electrographic (EC) signals from an isolated rat heart-a model that theoretically contains no inherent variability. LVP and EC signal data were acquired simultaneously during Langendorff perfusion of isolated rat hearts before and after the addition of acetylcholine (n = 11), norepinephrine (n = 12), or no drug (n = 12). Two-minute segments of the continuous LVP and EC signal data were analyzed by RQA. Findings showed that%recurrence,%determinism, entropy, maxline, and trend from the continuous LVP signal significantly increased in the presence of both acetylcholine and norepinephrine, although systolic LVP significantly increased only with norepinephrine. In the continuous EC signal, the RQA trend variable significantly increased in the presence of norepinephrine. These results suggest that when either the sympathetic or parasympathetic division of the autonomic nervous system overwhelms the other, the dynamics underlying cardiac variability become stationary. This study also shows that information concerning inherent variability in the isolated rat heart can be gained via RQA of the continuous cardiac signal. Although speculative, RQA may be a tool for detecting alterations in cardiac variability and evaluating signal dynamics as a nonlinear indicator of cardiac pathology.

Effect of estrogen on calcium-handling proteins, beta-adrenergic receptors, and function in rat heart.

Regulation of cellular Ca(2+) cycling is central to myocardial contractile function. Loss of Ca(2+) regulation is associated with cardiac dysfunction and pathology. Estrogen has been shown to modify contractile function and to confer cardioprotection. Therefore, we investigated the effect of estrogen on expression of rat heart myocardial Ca(2+)-handling proteins and beta-adrenergic receptor (beta(1)-AR) and examined functional correlates. Female rats were sham-operated (SHAM) or ovariectomized. Two weeks after ovariectomy rats were injected (i.p.) daily with estradiol benozoate (OVX+EB) or sesame oil (OVX) for 2 weeks. Protein abundance was measured by immunoblotting and mRNA was quantified by real-time RT-PCR. OVX significantly decreased estrogen and progesterone levels and EB replacement returned both estrogen and progesterone to physiological levels. OVX induced a 75% reduction of uterine weight and a gain in body weight. Replacement restored weights to SHAM level. OVX increased and estrogen-replacement normalized abundance of beta(1)-AR and L-type Ca(2+) channel (Cav1.2) protein. OVX decreased sodium-Ca(2+) exchange protein (NCX) and estrogen restored protein abundance to SHAM levels. Sarcoplasmic reticular ATPase (SERCA), phospholamban (PLB), and ryanodine receptor (RyR) abundance was not altered by hormone status. Levels of mRNA encoding for beta(1)-AR, Cav1.2, and NCX were not influenced by OVX or estrogen replacement. OVX had no effect on SERCA and PLB mRNA level but estrogen replacement elicited a significant increase compared to OVX and SHAM. Estrogen-dependent changes in Ca(2+)-handling proteins and beta(1)-AR are theoretically consistent reduced myocellular Ca(2+) load. However, hormone-dependent alterations in protein were not associated with changes in contractile function.

Sex differences in susceptibility to epinephrine-induced arrhythmias.

Gender differences in incidence of cardiac arrhythmias have been documented. It is generally believed that cardiac pathology provides an arrhythmogenic substrate but that a trigger such as sympathetic nervous system activation is required to initiate arrhythmias. This study was done to determine whether there is a sex difference in susceptibility to epinephrine-induced arrhythmias in healthy rats without preexisting pathology and to determine whether gonadal hormones play a role in development of arrhythmias. Untreated, sham-operated, and gonadectomized male and female rats were anesthetized and given IV boluses of epinephrine. ECG, heart rate, and blood pressure were measured continuously for 1 minute and intermittently over a period of 30 minutes. Male rat hearts have a higher occurrence and frequency of epinephrine-induced premature ventricular contractions, missed beats, and blocks than female rat hearts. Ovariectomy increases arrhythmias, thereby abolishing the female advantage. Castration has no effect on occurrence and frequency of premature ventricular contractions but attenuates missed beats and blocks. Sex differences and effect of gonadectomy on epinephrine-induced alterations in heart rate and blood pressure implicate baroreceptor reflex in the dimorphic arrhythmogenic response. Male rat hearts are more susceptible than female hearts to epinephrine-induced arrhythmias, and gonadal hormones play a role in this disparity.

Sex differences in ethanol liquid diet consumption in Sprague-Dawley rats.

There are reports of sex differences in ethanol intake between different strains of male and female rats; however, ethanol consumption (via an ethanol liquid diet) and blood ethanol levels (BELs) between male and female rats of the Sprague-Dawley strain have not been studied. Therefore, the aims of this study were to examine body growth, ethanol consumption (ml/day and g.kg(-1).day(-1)), and BELs in adult male and female (n=6-8 per group; sham-operated and ovariectomized) Sprague-Dawley rats consuming different concentrations (3% to 9% volume/volume) of the Lieber-DeCarli liquid ethanol diet. Throughout the study, male rats weighed significantly more than both female groups, and ovariectomized female rats weighed more than sham female rats. Ethanol diet consumption (ml/day) was significantly greater in male rats than in female rats at higher ethanol concentrations, whereas, when the diet consumption was expressed in grams of ethanol per kilogram of body weight per day, the sham female group was shown to consume significantly more ethanol than the male group. Even though there were differences in ethanol intake, BELs were similar among the groups. The data indicate that, similar to other strains, Sprague-Dawley rats also exhibit sex differences in their pattern of body growth (weight gain) and ethanol intake; however, BELs were similar among the groups.

Sex differences in expression of calcium-handling proteins and beta-adrenergic receptors in rat heart ventricle.

Human studies reveal sex differences in myocardial function as well as in the incidence and manifestation of heart disease. Myocellular Ca(2+) cycling regulates normal contractile function; whereas cardiac dysfunction in heart failure has been associated with alterations in Ca(2+)-handling proteins. Beta-adrenergic receptor (beta-AR) signaling regulates activity of several Ca(2+)-handling proteins and alterations in beta-AR signaling are associated with heart disease. This study examines sex differences in expression of beta(1)-AR, beta(2)-AR, and Ca(2+)-handling proteins including: L-type calcium channel (Ca(v)1.2) , ryanodine calcium-release channels (RyR), sarcoplasmic reticular Ca(2+) ATPase (SERCA2), phospholamban (PLB) and Na(+)-Ca(2+) exchange protein (NCX) in healthy hearts from male and female Sprague-Dawley rats. Protein levels were examined using Western blot analysis. Abundance of mRNA was determined by real time RT-PCR normalized to abundance of GAPDH mRNA. Contraction parameters were measured in right ventricular papillary muscle in the presence and absence of isoproterenol. Results demonstrate that female ventricle has significantly higher levels of Ca(v)1.2, RyR, and NCX protein compared to males. Messenger RNA abundance for RyR, and NCX protein was significantly higher in females whereas Ca(v)1.2 mRNA was higher in males. No differences were detected in beta-ARs, SERCA2 or PLB. Female right papillary muscle had a faster maximal rate of force development and decline (+/- dF/dt). There were no sex differences in response to isoproterenol. Results show significant sex differences in expression of key ventricular Ca(2+)-handling proteins that are associated with small functional differences in +/- dF/dt. Further studies will determine whether differences in the abundance of these key proteins play a role in sex disparities in the incidence and manifestation of heart disease.

New blood thinner offers first potential alternative in 50 years: ximelagatran.

Traditional anticoagulants employed in the treatment of thrombosis include the injectable heparins and oral warfarin. Though effective, these traditional agents are fraught with limitations in their ease of use in the clinical setting. Warfarin, for example, has many pharmacokinetic properties and food-and-drug interactions that result in unpredictable patient response and the need for expensive and time-consuming monitoring of coagulation status. Ximelagatran is a novel, promising, orally active, direct thrombin inhibitor currently in development that, for the first time in 50 years, offers a potential alternative to the mainstay oral agent "warfarin." Advantages of ximelagatran over warfarin include predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine anticoagulant monitoring, no clinically significant drug interactions, and fixed-dose administration. Ximelagatran has been evaluated for thromboprophylaxis following orthopedic surgery, acute treatment and secondary prevention of venous thrombosis, stroke prevention in atrial fibrillation, and acute coronary syndromes. Results of clinical trials suggest that ximelagatran is equally or more efficacious than warfarin and/or low-molecular-weight heparin therapy without increasing rates of minor or major bleeding. Although postmarketing surveillance will provide the final test of this drug, the future looks promising for addition of a new anticoagulant with the potential to provide excellent efficacy, predictable response, and reduced adverse effects. Pending regulatory approval, ximelagatran may help overcome barriers to appropriate anticoagulant therapy, thereby decreasing morbidity and mortality associated with thrombotic diseases.