Influence of immunosuppression and effect of hepatitis C virus on new onset of diabetes mellitus in liver transplant recipients.

INTRODUCTION: New-onset posttransplantation diabetes mellitus (PTDM), with an incidence of 10% to 30%, increased graft and patient morbidity and mortality. Such causal factors as age, obesity, therapy, immunosuppression, and hepatitis C virus (HCV) contribute to this disease. OBJECTIVE: We sought to determine the incidence of PTDM and impaired fasting glucose (IFG) concentration in transplant recipients to define the causal variables. MATERIAL AND METHODS: The study included 127 patients. Patients with pretransplantation diabetes and those with less than 6 months of follow-up were excluded. A descriptive observational study to assess the association between PTDM and IFG and the immunosuppression therapy used was performed by monitoring the potential confounding variables of age, obesity, and HCV. RESULTS: During mean follow-up of 73.7 months (range, 7-120 mo), 93 patients received cyclosporine A (CyA) and 34 received tacrolimus (Tac) therapy. Thirty patients (23.6%) developed PTDM or IFG including 15 (16%; PTDM, six IFG, nine) in the CyA group and 15 (PTDM, seven; IFG, eight) in the Tacrolimus group (P = .001; odds ratio [OR], 4.1). They were homogeneous with respect to confounding variables except for HCV (P = .01). Of the 55 patients with HCV infection, 12 developed PTDM or IFG, including three in the CyA group and nine in the tacrolimus group (P = .03; OR, 7.7), whereas in the 72 patients without HCV infection, the CyA or tacrolimus association with PTDM or IFG was significant (P = .05), Mantel-Haenszel test; OR, 4.9). The interaction between HCV and immunosuppression therapy was primarily produced in the IFG group (HCV-positive; P = .008; OR, 8). CONCLUSION: We observed an association between the use of tacrolimus and the development of PTDM or IFG. There is greater risk in HCV-positive patients, in particular in relation to IFG. The choice of immunosuppressive treatment might be decided on the basis of the patient's pretransplantation status.

The interplay of stress, gender and cognitive style in depressive onset.

Major depression is more common in women than men, but the reasons for this difference have not been completely understood. We examine recent evidence investigating whether sex differences in exposure or response to stressful life events play an explanatory role in the sex differences found in onset of depression. We also explore the possibility that sexual dimorphism in depressive prevalence and response to events is related to sex differences in cognitive style. We conclude that differences between women and men in response to stressful life events and cognitive style are relevant to understanding sex differences in the onset of depression.

Examining structured representation and designated fiscal support for women's health in the U.S. Department of Health and Human Resources.

The United States Department of Health and Human Services (DHHS) is committed to monitoring, protecting, and improving the health of the nation. We examine the structure established within DHHS to address the health of women; review initiatives generated by women's health offices, advisors, and coordinators within DHHS agencies; and contrast the budgets provided to women's health offices with those of the parent DHHS agencies. Data were obtained from DHHS and other public government documents, DHHS websites, contact with agency personnel, and literature review. Significant clinical, research, and educational efforts important to the health of women have resulted from representation for women's health within the DHHS. Yet, structured representation and designated fiscal support necessary to maintain and expand these efforts are variable and not guaranteed across agencies. Only one Office of Women's Health and one Senior Advisor position are supported by statute, one director's position for an Office of Women's Health has been downgraded in government rank, and two other women's health positions had their reporting structure changed, making them less centrally located in their respective agencies. During the last 4 years of unprecedented growth within DHHS, only one Office of Women's Health received consistent increases in budgeted dollars. There is a clear need to support and stabilize representation for women's health within DHHS in order to maintain current productive efforts, coordinate existing and developing initiatives, and integrate new topics of importance to women's health into each agency. This can be accomplished by establishing structured offices by statute and ensuring future funding commensurate with the mission of each office.

Sex differences in event-related risk for major depression.

BACKGROUND: This study sought to determine if women are more likely than men to experience an episode of major depression in response to stressful life events. METHOD: Sex differences in event-related risk for depression were examined by means of secondary analyses employing data from the Americans' Changing Lives study. The occurrence and time of occurrence of depression onset and instances of stressful life events within a 12-month period preceding a structured interview were documented in a community-based sample of 1024 men and 1800 women. Survival analytical techniques were used to examine sex differences in risk for depression associated with generic and specific stressful life events. RESULTS: Women were approximately three times more likely than men to experience major depression in response to any stressful life event. Women and men did not differ in risk for depression associated with the death of a spouse or child, events affecting their relationship to a spouse/partner (divorce and marital/love problems) or events corresponding to acute financial or legal difficulties. Women were at elevated risk for depression associated with more distant interpersonal losses (death of a close friend or relative) and other types of events (change of residence, physical attack, or life-threatening illness/injury). CONCLUSION: Stressful life events overall, with some exceptions among specific event types, pose a greater risk for depression among women compared to men.

Cortical instability and the mechanism of mania: a neural network simulation and perceptual test.

BACKGROUND: A previous neural network simulation suggested that manic states arise from excessive levels of noise that destabilize neural representations. The Necker cube stick figure provides a simple perceptual task that assesses stability of gestalt-type representations. METHODS: A neural network was developed that included a simulation of the Necker cube task. Noise was added to induce maniclike jumps from one representation to another. A parallel study of Necker cube perception was conducted with 16 patients diagnosed with manic-spectrum disorder, 18 patients with schizophrenia, and 19 normal control subjects. Cognitive speed and rate of indiscriminate responses were assessed using an auditory continuous performance task. RESULTS: During processing of the "Necker cube" stimulus, the reversal rate of the noise-destabilized "manic" network was increased by 30%. In the human subject study, the median score of Necker cube reversal rates for manic-spectrum patients was roughly twice that of normal control subjects and patients with schizophrenia. Accelerated reversal rates in the manic-spectrum group were not attributable to excessive cognitive speed or higher rates of indiscriminate responses. CONCLUSIONS: The two studies, considered together, support the hypothesis that excessive cortical noise destabilizes neural representations in manic-spectrum patients.

Antidepressant-associated mania and psychosis resulting in psychiatric admissions.

BACKGROUND: The safety and tolerability of the selective serotonin reuptake inhibitors and the newer atypical agents have led to a significant increase in antidepressant use. These changes raise concern as to the likelihood of a corresponding increase in adverse behavioral reactions attributable to these drugs. METHOD: All admissions to a university-based general hospital psychiatric unit during a 14-month period were reviewed. RESULTS: Forty-three (8.1%) of 533 patients were found to have been admitted owing to antidepressant-associated mania or psychosis. CONCLUSION: Despite the positive changes in the side effect profile of antidepressant drugs, the rate of admissions due to antidepressant-associated adverse behavioral effects remains significant.

Gender differences in referral to cardiac rehabilitation programs after revascularization.

BACKGROUND: This study examines the influence of gender on the healthcare provider's secondary prevention instruction and cardiac rehabilitation (CR) referral after coronary revascularization procedures such as balloon angioplasty/coronary stenting and coronary bypass surgery (CABG). Cardiac rehabilitation decreases mortality and morbidity, yet only a small percentage of women and men are referred to these programs. The patient population of our university-affiliated CR program consisted of 88% men and 12% women. METHODS: In a matched case observational study, 80 patients (40 men, 40 women) who had undergone coronary revascularization procedures between 1997 and 1998 completed a questionnaire on secondary prevention instruction and written referral to CR programs. Patients were matched for age and coronary revascularization procedure. RESULTS: Women were less likely to be instructed on secondary prevention strategies and CR or referred to CR as compared to men despite being matched for age and undergoing the same procedure. The data demonstrate a gender difference in hospital teaching and referral information for CR after revascularization (P < 0.001). Being a woman was associated with a decreased likelihood of receiving a physician referral to CR after revascularization (P < 0.001). CONCLUSION: The instruction of patients concerning secondary prevention and CR postrevascularization procedures is poor. Within that group, women were far less likely to have CR discussed or referrals made by healthcare professionals. This study demonstrates the need for education initiatives of all healthcare providers on the comprehensive nature and benefits of CR in the secondary prevention of cardiovascular disease, with a particular emphasis on women.

Genotyping of hepatitis C virus isolates using CLIP sequencing.

Determination of hepatitis C virus (HCV) genotypes and subtypes has become increasingly important for the clinical management and prognosis of HCV infections. The aim of the present study was to assess the specificity and reliability of a newly developed, commercially available HCV genotyping kit (TRUGENE HCV 5'NC genotyping kit). This technique utilizes PCR fragments previously generated by the diagnostic Roche AMPLICOR HCV test, which are subsequently subjected to simultaneous PCR amplification and direct sequencing (CLIP sequencing) of the 5' noncoding region (5'NCR). HCV isolates from 100 randomly chosen patients were genotyped by both the TRUGENE HCV 5'NC genotyping kit and DNA enzyme immunoassay (DEIA). Typing results obtained by both methods were in complete concordance in 91% of the cases. HCV RNA from the samples with discordant genotype assignment in both assays was additionally amplified with primers from the HCV core and NS5B regions. Phylogenetic analysis of the obtained sequences supported the results obtained from DEIA in six cases and CLIP sequencing in two cases. In the former six cases, the TRUGENE HCV 5'NC genotyping kit could not correctly differentiate between subtypes of genotypes 1 and 2 due to the high conservation of the 5'NCR. However, since there was not any misclassification between HCV genotypes 1 and non-1 types, the results obtained with this system are, in general, reliable and can be used in clinical practice. The TRUGENE HCV 5'NC genotyping kit in our hands proved to be a fast and convenient technique that might be an attractive option for HCV genotyping in laboratories already using the Roche AMPLICOR HCV test for diagnostic reverse transcription-PCR.

Multidisciplinary Women's health research: the national centers of excellence in women's health.

Contemporary research increasingly needs to consider the value of a multidisciplinary approach in answering critical health questions. The current article outlines the need for multidisciplinary investigations specifically in reference to women's health, and addresses issues related to generating and sustaining interest in such an approach. In addition, the importance of resources and environment for facilitating multidisciplinary research and advocacy efforts for obtaining funding for this approach are discussed. Methodological issues pertinent to the operationalization of multidisciplinary research in women's health are also addressed, and lessons learned from the National Centers of Excellence in initiating multidisciplinary research in women's health are reviewed.

Diagnostic criteria for traumatic grief.

This article reviews the rationale for the development of diagnostic criteria for Traumatic Grief. Traumatic Grief is a new nosologic entity that a panel of experts recently proposed. It is a direct descendent of the concept of pathologic grief, and it has roots in attachment behavior, separation distress, and traumatic distress. We present consensus, diagnostic criteria for Traumatic Grief and discuss them in relation to another recently proposed set of criteria. In conclusion, we recommend the development of empirically tested, consensus, diagnostic criteria for Traumatic Grief. Diagnostic criteria would facilitate early detection and intervention for those bereaved persons afflicted by this disorder and lead to additional studies of the prevalence, the nature, and the treatment of the disorder.

Development and preliminary psychometric properties of an instrument for the measurement of childhood trauma: the Early Trauma Inventory.

Research on the effects of childhood trauma has been limited by the lack of a comprehensive, reliable, and valid instrument that assesses the occurrence of early traumatic experiences. This paper presents the development and preliminary psychometric properties of an instrument, the Early Trauma Inventory (ETI), for the assessment of reported childhood trauma. The clinician-administered ETI is a 56-item interview for the assessment of physical, emotional, and sexual abuse, as well as general traumatic experience (including items which range from parental loss to natural disaster). For each item of the ETI, frequency of abuse/trauma by developmental stage, onset and termination of abuse/trauma, perpetrator of the abuse/trauma, and impact on the individual are assessed. Initial analyses indicate acceptable inter-rater reliability, test-retest reliability, and internal consistency for the ETI. Comparisons between the ETI and other instruments for the assessment of trauma, as well as instruments for the measurement of symptoms related to abuse, such as dissociation and PTSD, demonstrated good convergent validity. Validity was also demonstrated based on the ability of the ETI to discriminate patients with PTSD from comparison subjects. Based on these findings, the ETI appears to be a reliable and valid instrument for the measurement of reported childhood trauma.

Adverse life events and cognitive-personality characteristics in the prediction of major depression and antidepressant response.

OBJECTIVE: Stressful life events are known to precipitate major depression. However, it remains unclear why some individuals who experience adverse events develop depression whereas others do not, and how the occurrence of life events affects treatment outcome. Emerging models posit that the effect of adverse life events varies by cognitive-personality style. This study examines the direct and interactive effects of stressful life events and cognitive-personality style in predicting 1) episode onset in patients with DSM-IV unipolar depression versus community comparison subjects and 2) depressive symptom severity at the completion of a 6-week standard antidepressant regimen. METHOD: Multivariate models were used to test the effects of adverse life events, cognitive-personality style, and the congruence of event type (interpersonal versus achievement) with cognitive-personality style on depressive onset and treatment outcome in 43 patients with major depression and 43 healthy comparison subjects. Cognitive-personality characteristics were assessed by using Beck's measures of sociotropy (interpersonal dependency) and autonomy (need for independence and control). RESULTS: Adverse life events, sociotropy, and an autonomy factor need for control were each significantly related to depressive onset and predicted group status for 88% of the subjects. Event types affected outcome differently, and specific life event types interacted with cognitive-personality styles in predicting response to treatment. A multivariate model accounted for 65% of the variance in predicting outcome. CONCLUSIONS: Adverse life events are a potent factor in predicting depression. However, cognitive-personality characteristics also confer susceptibility to depression. Better outcome is associated with occurrence of adverse interpersonal events (e.g., death of a loved one) rather than adverse achievement events (e.g., loss of job) and occurs when the event type is congruent with cognitive-personality style.

Self-efficacy as a mediator between stressful life events and depressive symptoms. Differences based on history of prior depression.

BACKGROUND: Self-efficacy, a characteristic that is protective against depressive symptoms, may be undermined by stressful life events. AIMS: To estimate the effects of stressful life events on self-efficacy, and to examine self-efficacy as a mediator of the effect of stressful life events on symptoms of depression. METHOD: Using a sample of 2858 respondents from the longitudinal Americans' Changing Lives study, path analyses were used to evaluate interrelationships between self-efficacy, life events and symptoms of depression controlling for a variety of potentially confounding variables. Separate models were estimated for those with and without prior depression. RESULTS: For those with prior depression, dependent life events had a significant, negative impact on self-efficacy. For those without prior depression, life events had no effect on self-efficacy. CONCLUSIONS: For those with prior depression, self-efficacy mediates approximately 40% of the effect of dependent stressful life events on symptoms of depression.

Family accommodation of obsessive-compulsive symptoms: instrument development and assessment of family behavior.

Relatives frequently accommodate patients' obsessive-compulsive symptoms and clinicians hypothesize that such accommodations adversely affect patient outcome. This study's purpose was to develop a valid and reliable measure, the Family Accommodation Scale for Obsessive-Compulsive Disorder (FAS), and to investigate the family accommodation construct. We administered the FAS and additional family and patient measures to 36 adult obsessive-compulsive patients and their primary caregivers. The FAS demonstrated excellent interrater reliability and good internal consistency and performed well on assessment of its convergent and discriminant validity. Family accommodation was significantly associated with patient symptom severity and functioning, and with relatives' own obsessive-compulsive symptoms. Although most relatives accommodated patient symptoms, many did not believe that such accommodations improved the patient's clinical status. The FAS will provide researchers and clinicians with a useful tool for assessing family accommodation and for identifying families who may benefit from interventions aimed at developing more adaptive coping strategies.

Childhood sexual abuse as a risk factor for depression in women: psychosocial and neurobiological correlates.

OBJECTIVE: Depression is twice as common in women as in men, but the reason for this sexual dimorphism is unknown. This article reviews recent studies of the role of childhood sexual abuse in the subsequent development of major depressive disorder, and the biological and psychosocial mechanisms by which early stressors may contribute to adult-onset depression in women. Particular attention is paid to investigations of the long-term effects of early stress on hypothalamic-pituitary-adrenal (HPA) axis function. METHOD: Studies were identified by means of computerized and manual searches; further references were obtained from the bibliographies of reviewed articles. RESULTS: Childhood sexual abuse is associated with adult-onset depression in both men and women, and occurrence of such abuse is more common in girls than in boys. There is evidence from both animal and human studies that early stressors produce long-term dysregulation of the HPA axis similar to that seen in depressed patients and that such dysregulation results in a differential response to stressors in adulthood. In addition, it appears that the HPA axis in females may be more susceptible to stress-induced dysregulation, which might contribute to an increased vulnerability to depression in adulthood. CONCLUSIONS: Childhood sexual abuse is an important early stressor that may predispose individuals to adult-onset depression by means of dysregulation of the HPA axis. Investigation of the mechanisms mediating the relationship between childhood sexual abuse and adult-onset depression, and the study of gender differences in exposure to this and other stressors, may improve our understanding of the etiology of depressive illness in general.