Cerebral cavernous malformations arise independent of the heart of glass receptor.

BACKGROUND AND PURPOSE: The Heart of Glass (HEG) receptor binds KRIT1 and functions with KRIT1, CCM2, and PDCD10 in a common signaling pathway required for heart and vascular development. Mutations in KRIT1, CCM2, and PDCD10 also underlie human cerebral cavernous malformation (CCM) and postnatal loss of these genes in the mouse endothelium results in rapid CCM formation. Here, we test the role of HEG in CCM formation in mice and in humans. METHODS: We constitutively or conditionally deleted Heg and Ccm2 genes in genetically modified mice. Mouse embryos, brain, and retina tissues were analyzed to assess CCM lesion formation. RESULTS: In postnatal mice, CCMs form with Ccm2-/- but not with Heg-/- or Heg-/-;Ccm2+/- endothelial cells. Consistent with these findings, human patients with CCM who lack exonic mutations in KRIT1, CCM2, or PDCD10 do not have mutations in HEG. CONCLUSIONS: These findings suggest that the HEG-CCM signaling functions during cardiovascular development and growth, whereas CCMs arise because of loss of HEG-independent CCM signaling in the endothelium of the central nervous system after birth.

Familial and perceived risk of breast cancer in relation to use of complementary medicine.

AIM: To examine the use of complementary and alternative medicine (CAM) by women with varying levels of familial and perceived risk of breast cancer with the goal of preventing breast cancer. METHODS: Cross-sectional data on CAM use were collected on 2,198 women (mean age, 63 years) personally unaffected by breast cancer in the Minnesota Breast Cancer Family Study. CAM use was compared across women at high, moderate, or average risk based on family history, as well as across categories of perceived risk of breast cancer. CAM use was also examined in relation to screening and general health behaviors, worry about breast cancer, and optimism. RESULTS: Half (49.5%) of the women reported using at least one CAM modality with the intent of preventing breast cancer. Univariate analyses indicated that greater overall CAM use was related to greater perceived risk (P = 0.018), more general health behaviors (P < 0.0001), more breast cancer screening behaviors (P = 0.0002), greater optimism (P = 0.0002), and higher educational attainment (P < 0.0001). Multivariate analysis revealed that general health behaviors (P < 0.0001), education (P = 0.0027), and optimism (P = 0.037) were significant predictors of CAM use when in the same model with perceived risk and breast cancer screening behaviors. CONCLUSIONS: Many women use CAM with the goal of preventing breast cancer. General health-promoting behaviors, education, and optimism predict CAM use. Evidence-based guidance is needed for the public and health care providers on the potential and limitations of specific CAM approaches to affect cancer risk.

The value of massage therapy in cancer care.

Massage therapy is increasingly available as a supportive therapy to patients in medical centers providing cancer treatment. This article provides an overview of the evidence base relevant to the use of massage with the intended goal of alleviating symptoms and side effects experienced by cancer patients. Collectively, the available data support the view that massage, modified appropriately, offers potential beneficial effects for cancer patients in terms of reducing anxiety and pain and other symptoms. Replication of preliminary studies with larger, more homogeneous patient samples and rigorous study designs will help to clarify which massage modalities have the most potential benefit for which patients before, during, and after specific types of cancer treatment.

Complementary and alternative therapy use in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Little information is available on the use of complementary and alternative medicine (CAM) in long-term survivors of childhood and adolescent cancer. PROCEDURE: The Childhood Cancer Survivor Study (CCSS) is a resource evaluating the long-term effects of cancer and associated therapies in 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986 before the age of 21 years. A survey of CAM use during the previous year was distributed in 2000-2001 and completed by 9,984 survivors and 2,474 sibling controls. RESULTS: CAM use reporting was similar in cases (39.4%) and siblings (41.1%). Compared to female siblings, female survivors were more likely to use biofeedback (odds ratio (OR) = 3.3; 95% CI = 1.0-10.8) and hypnosis/guided imagery (OR = 3.2; 95% CI = 1.6-6.8); male survivors were more likely than male siblings to use herbal remedies (OR = 1.3; 95% CI = 1.1-1.6). Factors associated with CAM use in survivors included elevated scores on the brief symptom inventory (BSI)-18 (OR = 1.6; 95% CI = 1.3-1.9), prolonged pain (OR = 1.5; 95% CI = 1.3-1.7), and having seen a physician in the past 2 years (OR = 1.6; 95% CI = 1.4-1.8). Survivors reporting low alcohol intake and excellent or good general health reported lower levels of CAM use (OR = 0.7; 95% CI = 0.7-0.8 and OR = 0.8; 95% CI = 0.7-0.9, respectively). CONCLUSIONS: Survivors have a similar reported use of CAM compared to a sibling cohort. However, our data suggest that survivors turn to CAM for specific symptoms related to previous diagnosis and treatment. Future research is needed to determine whether CAM use reflects unmet health needs in this population.

Coping predictors of children's laboratory-induced pain tolerance, intensity, and unpleasantness.

UNLABELLED: This study examined coping predictors of laboratory-induced pain tolerance, intensity, and unpleasantness among 244 healthy children and adolescents (50.8% female; mean age, 12.73 +/- 2.98 years; range, 8-18 years). Participants were exposed to separate 4-trial blocks of pressure and thermal (heat) pain stimuli, as well as 1 trial of cold pain stimuli. Strategies for coping with pain were measured using the Pain Coping Questionnaire (PCQ). Linear regression analyses were conducted to examine the associations between the 8 PCQ subscales and pain responses (pain tolerance, intensity, and unpleasantness) to all 3 pain tasks, controlling for age and sex. We found that internalizing/catastrophizing predicted higher pain intensity across the 3 pain tasks and higher cold pain unpleasantness; seeking emotional support predicted lower pressure pain tolerance; positive self-statements predicted lower pressure pain intensity and lower cold pain intensity and unpleasantness; and behavioral distraction predicted higher pressure pain tolerance and lower heat pain unpleasantness. These results suggest that in healthy children, internalizing/catastrophizing, and seeking emotional support may be conceptualized as pain-prone coping strategies, and positive self-statements and behavioral distraction as pain-resistant coping strategies within the context of laboratory pain. PERSPECTIVE: These results support investigation of interventions with children that aim to reduce acute pain responses by modifying coping to reduce seeking of emotional support and catastrophizing and enhance the use of positive self statements and behavioral distraction.

Self-care behaviors associated with myofascial temporomandibular disorder pain.

AIMS: To document the frequency of self-care in a clinical sample of patients with myofascial temporomandibular disorder (TMD) pain; report the perceived relief and control of pain for each of the self-care behaviors; and to test for associations between the frequency and efficacy of each self-care behavior and pain, depression and sleep quality, as assessed during a clinical visit, and to determine whether the frequency was associated with changes in pain intensity, depression, and sleep quality 30 days later. METHODS: The sample consisted of 99 female and 27 male myofascial TMD pain patients who were participants in a multidisciplinary facial pain evaluation program. The subjects participated in a structured interview during a clinical visit and a follow-up telephone interview 30 days later. The interviews included questions about self-care, including resting, relaxation techniques, massage, hot and/or cold packs, home remedies, stretching or exercise, herbal remedies, and the use of vitamins or nutritional supplements for pain. RESULTS: The passive self-care behaviors, such as resting when experiencing pain (66%) and relaxation techniques (62%), were the most commonly used. Patients reported that hot or cold packs (5.3, 0-to-10 scale) and massage (4.7) provided the greatest relief from pain, whereas resting (4.9), relaxation (4.8), and massage (4.8) resulted in the greatest ability to control pain. The most striking finding was that initial levels of pain or change in pain were not consistently associated with self-care use; however, psychosocial outcomes of depression and sleep quality were associated with self-care frequency and reported efficacy and improved in relation to patient-reported self-care frequency. CONCLUSION: Since people with chronic myofascial TMD pain engage in a range of pain self-care strategies, clinicians need to discuss self-care with patients regularly.

Complementary and alternative medicine for persistent facial pain.

This article discusses complementary and alternative medicine (CAM), reviews literature on the prevalence of use of CAM by the general adult population in the United States and by patients with persistent facial pain, and summarizes published, peer-reviewed reports of clinical trials assessing the effects of CAM therapies for persistent facial pain. Results indicate that many patients use CAM for musculoskeletal pain, including persistent facial pain. Preliminary work on selected complementary therapies such as biofeedback, relaxation, and acupuncture seems promising; however, there are more unanswered than answered questions about cost-effectiveness, efficacy and mechanisms of action of CAM for persistent facial pain.

Parent and child anxiety sensitivity: relationship to children's experimental pain responsivity.

UNLABELLED: Anxiety sensitivity (AS) or fear of anxiety sensations has been linked to childhood learning history for somatic symptoms, suggesting that parental AS may impact children's responses to pain. Using structural equation modeling, we tested a conceptual model in which parent AS predicted child AS, which in turn predicted a hypothesized latent construct consisting of children's pain intensity ratings for 3 laboratory pain tasks (cold pressor, thermal heat, and pressure). This conceptual model was tested in 211 nonclinical parent-child pairs (104 girls, 107 boys; mean age 12.4 years; 178 mothers, 33 fathers). Our model was supported in girls only, indicating that the sex of the child moderated the hypothesized relationships. Thus, parent AS was related to child laboratory pain intensity via its contribution to child AS in girls but not in boys. In girls, 42% of the effect of parent AS on laboratory pain intensity was explained via child AS. In boys, there was no clear link between parent AS and child AS, although child AS was predictive of experimental pain intensity across sex. Our results are consistent with the notion that parent AS may operate via healthy girls' own fear of anxiety symptoms to influence their responses to laboratory pain stimuli. PERSPECTIVE: The present study highlights sex differences in the links among parent and child anxiety sensitivity (fear of anxiety sensations) and children's experimental pain responses. Among girls, childhood learning history related to somatic symptoms may be a particularly salient factor in the development of anxiety sensitivity and pain responsivity.

Sex, gender, and age: contributions to laboratory pain responding in children and adolescents.

UNLABELLED: A cross-sectional design across late childhood and adolescence examined the influence of sex, gender socialization, and age on responses to controlled laboratory pain tasks. Healthy children and adolescents (n = 240, 50% female, age 8 to 18 years) completed the Child Sex Role Inventory, a self-report measure of identification with stereotypically masculine and feminine personality traits, as an index of gender socialization and participated in pressure, cold pressor, and heat pain tasks. Pain tolerance, pain intensity, and bothersomeness of each pain task were assessed. Masculinity correlated with lower heat pain ratings in boys but not girls. Logistic regression indicated cold pain intensity ratings were predicted by sex, gender score, and the age-by-gender score interaction. Heat pain intensity was predicted by age, gender score, age-by-gender score interaction, and sex-by-gender score. PERSPECTIVE: The current findings support closer examination of the influence of gender socialization on young people's pain responses and highlight the importance of a multifactorial, developmental approach to studying the impact of gender socialization on the emergence of sex differences in pain responses after puberty.

Pain and use of complementary and alternative medicine in a national sample of persons living with HIV.

The current study investigated the relationship of pain to use of complementary and alternative medicine (CAM) in a U.S. nationally representative sample of 2466 persons with human immunodeficiency virus (HIV), using data from the HIV Cost and Services Utilization Study. Pain was conceptualized as a need characteristic within the context of predisposing, enabling, and need (PEN) characteristics following Andersen's Behavioral Model of Health Services Use. Multivariate analyses were used to examine the association of baseline PEN characteristics with CAM use by follow-up (approximately 6 months later), including use of five specific CAM domains. Change in pain from baseline to follow-up was also examined in relation to CAM use. Baseline pain was a strong predictor of CAM use, and increased pain over time was associated with use of unlicensed or underground drugs with potential for harm. These results highlight the importance of medical efforts to control pain in persons living with HIV.

Gender role expectations of pain: relationship to experimental pain perception.

The primary purpose of this study was to investigate the influence of an individual's Gender Role Expectations of Pain (GREP) on experimental pain report. One hundred and forty-eight subjects (87 females and 61 males) subjects underwent thermal testing and were asked to report pain threshold, pain tolerance, VAS ratings of pain intensity and unpleasantness, and a computerized visual analogue scales (VAS) rating of pain intensity during the procedure. Subjects completed the GREP questionnaire to assess sex-related stereotypic attributions of pain sensitivity, pain endurance, and willingness to report pain. Consistent with previous research, significant sex differences emerged for measures of pain threshold, pain tolerance, and pain unpleasantness. After statistically controlling for age, GREP scores were significant predictors of threshold, tolerance, and pain unpleasantness, accounting for an additional 7, 11, and 21% of the variance, respectively. Sex remained a significant predictor of pain tolerance in hierarchical regression analyses after controlling for GREP scores. Results provide support for two competing but not mutually exclusive hypotheses related to the sex differences in experimental pain. Both psychosocial factors and first-order, biological sex differences remain as viable explanations for differences in experimental pain report between the sexes. It appears that GREP do play a part in determining an individual's pain report and may be contributing to the sex differences in the laboratory setting.

Racial/ethnic differences in the experience of chronic pain.

The purpose of this study was to examine racial/ethnic-related differences in a four-stage model of the processing of chronic pain. The subjects were 1557 chronic pain patients (White=1084, African American=473) evaluated at a pain management clinic at a large southeastern university medical center. Using an analysis of covariance controlling for pain duration and education, African American patients reported significantly higher levels of pain unpleasantness, emotional response to pain, and pain behavior, but not pain intensity than Whites. Differences were largest for the unpleasantness and emotion measures, particularly depression and fear. The groups differed by approximately 1.0 visual analogue scale unit, a magnitude that may be clinically significant. Racial/ethnic differences in the linear relationship between stages were also tested using structural equation modeling and LISREL-8. The results indicate differences in linear associations between pain measures with African Americans showing a stronger link between emotions and pain behavior than Whites.

Cavopulmonary assist in the neonate: an alternative strategy for single-ventricle palliation.

BACKGROUND: Cavopulmonary blood flow, rather than a systemic arterial source of pulmonary blood flow, stabilizes Norwood physiology. We hypothesized that pump-assisted cavopulmonary diversion would yield stable pulmonary and systemic hemodynamics in the neonate. This was tested in a newborn animal model of total cavopulmonary diversion and univentricular Fontan circulation. METHODS: Lambs (n = 13; mean weight, 5.6 +/- 1.5 kg; mean age, 6.8 +/- 4.0 days) were anesthetized and mechanically ventilated. Baseline hemodynamic parameters were measured. Total cavopulmonary diversion was performed with bicaval venous-to-main pulmonary artery cannulation. A miniature centrifugal pump was used to assist cavopulmonary flow. Support was titrated to normal physiologic parameters. Hemodynamic data, arterial blood gases, and lactate values were measured for 8 hours. Baseline, 1-hour, and 8-hour time points were compared by using analysis of variance. RESULTS: All animals remained stable without the use of volume loading, inotropic support, or pulmonary vasodilator therapy. Cardiac index, systemic arterial pressure, left atrial pressure, and lactate values were similar to baseline values 8 hours after surgery. Mean pulmonary arterial pressure and pulmonary vascular resistance were modestly increased 8 hours after surgery. Mean arterial pH, Po(2), and Pco(2) values remained stable throughout the study. CONCLUSIONS: Cavopulmonary assist is feasible in a neonatal animal model of total cavopulmonary diversion and univentricular Fontan circulation with acceptable pulmonary arterial pressures and without altering regional volume distribution or cardiac output. Pump-assisted cavopulmonary diversion, in combination with Norwood aortic arch reconstruction, could solve several major problems associated with a systemic shunt-dependent univentricular circulation, including hypoxemia, impaired diastolic coronary perfusion, and ventricular volume overload.

Cavopulmonary assist: circulatory support for the univentricular Fontan circulation.

BACKGROUND: Following Fontan palliation, the univentricular circulation is notable for coexisting systemic venous hypertension and pulmonary arterial hypotension. Assisted cavopulmonary blood flow to overcome this pressure gradient would restore the circulation to one more closely resembling normal two-ventricle physiology. We hypothesized that mechanical augmentation of cavopulmonary blood flow would provide physiologic stability in a model of cavopulmonary diversion and univentricular circulation. METHODS: Yearling sheep (n = 13, mean weight 56.5 kg) underwent total cavopulmonary diversion on cardiopulmonary bypass. The superior and inferior vena cavae were anastomosed directly to the right pulmonary artery. Axial flow pumps were positioned within both vena cavae to assist blood flow from the systemic venous circulation into the pulmonary vasculature. Baseline ventilation was resumed, cardiopulmonary bypass was weaned, and pump support was titrated to obtain normal physiologic measurement. Cardiopulmonary data were collected for 6 hours. RESULTS: All animals demonstrated hemodynamic stability without need for volume loading, inotropic support, or pulmonary vasodilator therapy. Cardiac output, pulmonary vascular resistance, pulmonary arterial pressure, inferior vena caval pressure, and arterial pCO(2) and pO(2) values 6 hours after intervention were similar to baseline values. Arterial lactate levels steadily decreased throughout the cavopulmonary assist period. CONCLUSIONS: Cavopulmonary assist with a percutaneous pump provides physiologic stability in a model of total cavopulmonary diversion and univentricular Fontan circulation without altering regional volume distribution or cardiac output. This mode of circulatory support may have potential to benefit patients with marginal Fontan hemodynamics in both the early and late time periods.

Psychosocial contributions to sex-correlated differences in pain.

Sex-correlated differences in pain perception and behavior have been reported in several studies. Where such differences are found, they are most often in the direction of girls and women reporting more pain than is reported by boys and men. Although biologic, psychologic, and sociocultural factors act interdependently to influence pain responding, most efforts to explain sex-correlated differences in pain have focused on first-order biologic differences between the sexes. The current paper discusses empirical and theoretical literature addressing gender role socialization, cognitive factors, and affective factors associated with sex-correlated differences in pain. We affirm that there is convincing evidence that such psychosocial factors must be taken into account in research on sex-correlated differences in pain. We contend that the use of the dichotomous variable sex as a proxy for presumed biologic aspects of being female or male may obscure the contribution to sex-correlated differences that could be ascribed to the ways in which women and men are socialized with respect to pain perception and pain reporting.

A review of complementary and alternative medicine use for treating chronic facial pain.

BACKGROUND: The authors compiled information on the prevalence of complementary and alternative medicine, or CAM, use, as well as on reports of randomized clinical trials of CAM modalities used to treat chronic facial pain. TYPES OF STUDIES REVIEWED: The authors searched several databases for reports of clinical trials randomizing patients who had facial pain to a CAM intervention or to a control or comparison group. Search terms included "complementary," "alternative," "acupuncture," "biofeedback," "relaxation," "herbal," "meditation," "massage," "yoga," "chiropractic," "homeopathic" and "naturopathic." RESULTS: Three acupuncture trials, eight biofeedback trials and three relaxation trials met the authors' inclusion criteria. Across studies, results suggested that acupuncture, biofeedback and relaxation were comparable to conservative treatment (for example, an intraoral appliance) and warranted further study. The authors did not locate any randomized clinical trials that tested the effects of homeopathy, naturopathy, chiropractic, massage, meditation, yoga or herbal remedies for chronic facial pain. CLINICAL IMPLICATIONS: Significant gaps in the scientific knowledge base limit the accuracy with which dental professionals can guide their patients regarding CAM approaches used to treat chronic facial pain.

Psychological considerations in the diagnosis and management of temporomandibular disorders and orofacial pain.

The past several decades have heralded new insights into the many ramifications of pain. The mind-body connection must be appreciated in the assessment and care of the temporomandibular disorder/orofacial pain patient. Recognizing key indicators of psychological distress and their impact on the total pain experience is essential to optimizing treatment outcomes. It currently is understood that pain, especially chronic or recurrent pain, crosses all disciplines of health care with regard to diagnosis and management. This article will discuss the importance of including clinical and health psychology as a part of the health care team.

Mechanisms of systemic adaptation to univentricular Fontan conversion.

OBJECTIVE: After univentricular Fontan conversion, systemic venous pressure serves as the sole driving force for transpulmonary blood flow. Consequently, systemic venous return is markedly altered and ventricular filling is subnormal. The mechanisms and time course of systemic adaptation to Fontan conversion are incompletely understood. We hypothesized that acute elevation in systemic venous pressure induces an adaptive response similar to conversion to a univentricular Fontan circulation. METHODS: Adjustable vessel occluders were placed around the superior and inferior vena cavae in juvenile sheep. After 1-week recovery, occluders were tightened to acutely increase and maintain systemic venous pressure at 15 mm Hg (n = 6), simulating 1-stage Fontan conversion. Control animals (n = 4) received identical surgery, but venous pressure was not manipulated. RESULTS: Cardiac index decreased significantly (3.9 ± 1.0 mL/min/m(2) to 2.7 ± 0.7 mL/min/m(2), P < .001) and then normalized to control at 2 weeks. Circulating blood volume increased (100 ± 9.4 mL/kg vs 85.5 ± 8.4 mL/kg, P = .034) as a persistent response. Cardiac reserve improved and was not different from control by week 3. Resting heart rate decreased in both groups. Oxygen extraction (arteriovenous oxygen difference) and neurohormonal mediators increased transiently and then normalized by week 2. CONCLUSIONS: Adaptation to global elevation in systemic venous pressure to Fontan levels is complete within 2 weeks. Increased blood volume and reduced heart rate are persistent responses. Increased oxygen extraction and neurohormonal up-regulation are temporary responses that normalize with recovery of cardiac output. With improved physiologic understanding of systemic adaptation to Fontan conversion, approaches to single-ventricle palliation can be more objectively assessed and optimized.

Sex differences in the relationship between maternal negative life events and children's laboratory pain responsivity.

OBJECTIVES: Previous research has demonstrated links between psychosocial factors, including negative life events (NLE) and pain in children. This study examined sex differences in the relationship among mother-reported NLE, child NLE, mother somatization, and children's laboratory pain responses for heat, cold, and pressure pain tasks. We predicted that maternal NLE would be moderately associated with girls' pain responses but would not be associated with boys' pain responses. METHOD: Participants were 176 nonclinical children (89 boys) aged 8 to 18 years (mean = 12.2, SD = 2.7) and their mothers. Mothers and children completed questionnaires assessing their perceptions of NLE experienced in the previous 12 months. RESULTS: Contrary to predictions, maternal NLE were related to pain responses in both boys and girls, although in opposite directions. Thus, increased maternal stress was associated with increased pain responses in girls but with decreased pain responses in boys. In addition, the impact of maternal NLE was only apparent for heat and pain tasks, indicating differential effects for various types of pain. CONCLUSION: The current findings underscore the importance of family variables in understanding sex differences in children's pain. Future research is needed to examine the mechanisms within the parent-child relationship that contribute to sex-differentiated pain outcomes, particularly under conditions of exacerbated parental stress.

Anxiety sensitivity and catastrophizing: associations with pain and somatization in non-clinical children.

This study examined the relationships among anxiety sensitivity (AS), catastrophizing, somatization and pain in 240 non-clinical children (121 girls; mean age = 12.7 years). Children with pain problems (n = 81; 33.8%) reported greater AS and catastrophizing (ps < .01) relative to children without pain problems. AS but not catastrophizing was significantly associated with current pain. However, both AS and catastrophizing were significantly associated with somatization. AS and catastrophizing represent related but partially distinct cognitive constructs that may be targeted by interventions aimed at alleviating pain and somatization in children.