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Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations.

UNLABELLED: Calcium channel antagonism in RyR2 defects. INTRODUCTION: Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations. METHODS AND RESULTS: Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. CONCLUSIONS: This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.

Calcium Channel Blockers↗

Rehabilitation and quality-of-life issues in patients with extremity soft tissue sarcoma.

The current standard of care for soft tissue sarcoma (STS) is limb salvage surgery and adjuvant radiotherapy, with long-term survival rates of approximately 70%. However, the extensive surgical resection and subsequent reconstruction result in 50% of survivors living with chronic disability. Rehabilitation aims to optimize functional independence and quality of life, and is routinely offered to patients undergoing surgical treatment for STS. Unfortunately, there is a dearth of research related to rehabilitation in this area. We propose a model for assessing disability, for designing treatment interventions and for evaluating rehabilitative outcomes in STS. The World Health Organization's (WHO) international classification of functioning, disability, and health (ICF) is divided into three domains: 1) impairments (related to body structure and function), 2) activity limitations (related to usual self-care activities/activities of daily living), and 3) participation restrictions (related to social roles). A literature review of STS rehabilitation reveals that most studies have focused on disability assessment, with few papers describing or evaluating rehabilitation interventions commonly employed in STS. Clinicians are forced to extrapolate findings from other patient populations in order to evaluate the effectiveness of specific rehabilitation strategies (ie, those used for particular sequelae of STS, such as lymphedema or impaired exercise tolerance). There is strongest support for complex decongestive physiotherapy (targeting lymphedema) and aerobic exercise interventions (aimed at alleviating cancer-related fatigue and psychosocial sequelae). The most poorly researched topic is rehabilitation for genitourinary disability (both incontinence and sexual dysfunction). Most studies related to oncologic rehabilitation are restricted to the impairment level (eg, affecting range of motion, muscle strength) of the ICF, with only a small minority addressing activity limitations (eg, affecting activities of daily living) experienced by patients. A consideration of participation restrictions (eg, fulfillment of vocational roles) is almost wholly absent from the literature. Yet social role reintegration is of fundamental importance to patients. Further research is required in these two domains. The ICF provides a comprehensive framework for future research into rehabilitation interventions for STS.

Extremities↗

A case of a methadone-induced movement disorder.

OBJECTIVE: To increase awareness of the possibility of opioid induced movement disorders. SETTING: A university-affiliated Veterans Affairs Hospital. PATIENT: A patient with upper extremity pain due to complex regional pain syndrome type I (reflex sympathetic dystrophy). INTERVENTIONS: Attempted pain control with methadone. RESULTS AND CONCLUSIONS: After failing many attempts at control, the authors were able to provide their patient significant pain relief from her complex regional pain syndrome type I using methadone. Unfortunately, the patient eventually developed a movement disorder, characterized by tremor, choreiform movements, and a gait abnormality, probably related to this opioid. The authors conclude that, while this type of movement disorder is uncommon, clinicians need to be aware of opioid-induced movement disorders, because they are disturbing to patients and often easily treated.

Adult↗

Rethinking target discovery in polygenic diseases.

Despite an extraordinary investment in R&D the yield of successful new drugs has been disproportionately low in recent years, suggesting that the whole process of drug development requires rethinking and reform. Most analyses on this issue focus on molecular target discovery considerations. Target identification is characterized by a surplus of potential targets, but there is a translational bottleneck primarily due to limitations of currently employed target validation platforms. Meanwhile, the clinical entities, to which treatments are directed, are also highly complex in terms of pathophysiologic mechanisms and manifestations. In the present study we discuss the limitations of current molecular target discovery approaches mainly in regard to selectivity and efficacy. We also describe the constraints imposed on drug development by the current diagnostic constructs and the tendency towards dissecting the complex clinical phenotypes to component intermediate phenotypes. Finally, we describe how the reconsideration of molecular and clinical targets in polygenic diseases may lead to new strategies of pharmacological intervention directed against component dysfunctions, rather than the whole complex phenotype. Such strategies involve the combination of single ligands that act selectively on multiple molecules involved in a particular disease, or the employment of "multi-targeted" drugs, i.e. single drug molecules that hit selectively multiple receptors sharing common binding sites.

Animals↗

Mathematical models of the transmission and control of sexually transmitted diseases.

BACKGROUND: The development of mathematical models to describe and interpret the epidemiology of sexually transmitted infections has involved the incremental addition of various forms of biological and behavioral complexity to simple mathematical templates. GOAL: To review simple and complex models used in study of observed epidemiologic pattern. STUDY DESIGN: An overview of modeling in sexually transmitted disease epidemiology identifies the function of different types of models. RESULTS: Simple models have the advantage of transparency and analytical tractability and can illustrate the relative merits of different intervention options. However, real life is replete with complexities that can have effects that are difficult to predict in the absence of a mathematical framework. CONCLUSIONS: Research should increasingly be based on robust parameterization of model structures and try to capture individual behaviors. Progress will be most rapid by interdisciplinary work where the clinician, epidemiologist, and mathematician work collaboratively to help improve our knowledge of how to best control infection and disease.

Female↗

Aneurysmal subarachnoid haemorrhage--Part 2: Post-operative nursing management diagnosis, complications and treatment: a composite case study.

Patients who have been diagnosed with an Aneurysmal Subarachnoid Haemorrhage (ASAH) frequently require surgical intervention to prevent further complications. Due to the complex nature of ASAH it is imperative to be meticulous in monitoring the patient's neurological condition. This is even more relevant post operatively as complications such as cerebral vasospasm peak incidence is between days four to fourteen and as well as complications of surgical and medical intervention may become evident.

Angioplasty, Balloon↗

Anomalous origin of one pulmonary artery from the ascending aorta: 36 years' experience from one centre.

UNLABELLED: Anomalous origin of one pulmonary artery from the ascending aorta is an uncommon lesion with an uncertain outcome. We reviewed 16 consecutive children (9 males) presenting with this lesion over a 36 year period at a single institution. Median age at presentation was 2 days (range, birth to 3.2 years). The anomalous pulmonary was the right in 12 and the left in 4, all originating from the proximal ascending aorta, with no patient having stenosis at the origin of the anomalous pulmonary artery. Associated cardiac anomalies were noted in 9 patients. No intervention was attempted in 2 patients: one was deemed inoperable due to complex associated lesions and pulmonary vascular obstructive disease, while the other one died before repair. Surgical intervention was attempted in 14 patients, with 3 intraoperative deaths (21%). Of 11 operative survivors, 8 developed pulmonary arterial stenosis graded severe in 2, moderate in 1 and mild in 5. Patients with severe stenosis required surgical angioplasty, 1 after unsuccessful dilation combined with placement of an endovascular stent. One patient with moderate, and one with mild, stenosis underwent successful transcatheter balloon dilation. The remaining 4 patients with mild stenosis remain unchanged during follow-up. One patient had biopsy evidence of pulmonary vascular obstructive disease at 3.3 years of age. There were no late deaths, giving a total mortality of 25% (4/16). CONCLUSION: While early diagnosis and repair of anomalous origin of one pulmonary artery from the ascending aorta is necessary, restenosis of the site of repair is common.

Aorta↗

Psychiatry: mindless or brainless, both or neither?

After a period marked by one-sided emphasis on psychodynamics and social issues, or what could be called "brainless" psychiatry on account of its relative neglect of cerebral processes, we are witnessing an opposite trend towards extreme biologism or "mindless" psychiatry. The pendulum has swung periodically from one to the other of these reductionistic positions throughout the history of psychiatry. The author argues that neither brainless nor mindless psychiatry can do justice to the complexity of mental illness and to the treatment of patients. Psychiatry's distinguishing feature as a clinical discipline is its equal concern with subjective experience, or the mind, and with the body, including brain function, which together constitute a person, a psychiatrist's proper focus of inquiry and intervention. Moreover, a person, viewed as a mindbody complex, is in constant interaction with the environment. It follows that both study of mental illness and clinical practice need to take into account the psychological, the biological and the social aspects. These three aspects are not mutually reducible and are indispensable for the understanding and treatment of the individual patient. Such a comprehensive, biopsychosocial approach provides an antithesis to the reductionistic viewpoints and, in the writer's opinion, is both practically and theoretically most satisfying.

Attitude of Health Personnel↗

[Physical exercise and yoga in prevention and treatment of addictive diseases].

Prevention of addictive diseases should be complex and systematic and it should include training of social skills, decision-making skills, family intervention, etc. Similarly, effective treatment is usually long-term, systematic and complex. Physical exercise and yoga can be useful components of comprehensive prevention and treatment programmes. On the other hand, competitive professional sport rather increases the number of risk factors for substance-related problems. Practical experience with the use of yoga in substance dependent patients and pathological gambles are mentioned. One of the advantages of yoga is the integration of physical exercise and relaxation.

Behavior, Addictive↗

Diabetes in adolescence: effects of multifamily group intervention and parent simulation of diabetes.

Insulin-dependent diabetes mellitus (IDDM) is a complex, chronic disease that is difficult to control during adolescence. This study evaluated the effects of a 6-week, family-oriented, group intervention on adolescents' metabolic control and psychosocial and family functioning. Thirty-two families were randomly assigned to one of three groups: multifamily (MF), multifamily plus parent simulation of diabetes (MF + S), and control (C). Outcome measures included glycosylated hemoglobin (Hb Al); perceptions of diabetes; estimates of youngsters' self-care; and family functioning. Adolescents in the MF + S group displayed significant decrements in Hb Al, and adolescents in both intervention groups reported more positive perceptions of a "teen-ager with diabetes" at posttreatment, relative to controls. Adolescents participating in smaller family groups demonstrated clinically significant improvements in Hb Al that were maintained at 6-month follow-up. Parent reports suggested that adolescents in the intervention groups improved their diabetes care. Findings support the use of multifamily groups plus parent simulation of diabetes as an intervention strategy for adolescents with IDDM.

Adolescent↗

The expert consensus guideline series. Pharmacotherapy of depressive disorders in older patients.

OBJECTIVES: Depression in older patients contributes to personal suffering and family disruption and increases disability, medical morbidity, mortality, suicide risk, and healthcare utilization. The majority of clinical trials of antidepressant treatments are conducted in younger patients. For this reason, clinicians often have to extrapolate from studies in populations that do not present the same problems as older patients. For example, older patients often have serious coexisting medical conditions that may contribute to the depression and complicate the choice of treatment. Older patients as a rule need to be on many medications, some of which may contribute to depression and/or interact with antidepressants. Finally, older adults metabolize medications slowly and are more sensitive to side effects than younger patients. Because of these complexities, we conducted a consensus survey of expert opinion on the pharmacotherapy of depressive disorders in older patients to address clinical questions not definitively answered in the research literature. METHOD: After reviewing the literature and convening a work group of experts, we prepared a written survey with 64 questions that asked about 857 options. 618 of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For the other options, the experts were asked to write in answers (e.g., average doses) or to check a box to indicate their preferred answer. We sent the survey to 50 national experts on geriatric depression, all of whom completed it. Consensus on each option was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 89% of the options rated on the 9-point scale. The experts stress the importance of identifying coexisting medical conditions that may be contributing to the depression or complicate treatment. For unipolar nonpsychotic major depression, the preferred strategy is an antidepressant (selective serotonin reuptake inhibitor [SSRI] or venlafaxine XR preferred) plus psychotherapy. For unipolar psychotic major depression, the treatment of choice is an antidepressant (SSRI or venlafaxine XR) plus one of the newer atypical antipsychotics. Electroconvulsive therapy is also first line. For dysthymic disorder or persistent milder depression, the experts recommend combining an antidepressant (SSRIs preferred) and psychotherapy. If the patient has a comorbid medical condition (e.g., hypothyroidism) that is contributing to the depression, the experts recommend treating both the depression and the medical condition from the outset. The SSRIs were the top-rated antidepressants for all types of depression. Among them, the experts gave the highest ratings for efficacy and tolerability to citalopram and sertraline. Paroxetine was another first-line option, and fluoxetine was rated high second line. The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy, supportive psychotherapy, problem-solving psychotherapy, and interpersonal psychotherapy. The experts also give strong support to including appropriate psychosocial interventions (e.g., psychoeducation, family counseling, visiting nurse services) in the treatment program. The majority of experts would continue treatment with antidepressant medication for at least 1 year if a patient has had a single episode of severe unipolar major depression, for 1-3 years for a patient who has had 2 such episodes, and for longer than 3 years if there is a history of 3 or more episodes. CONCLUSIONS: The experts reached a high level of consensus on the appropriateness of including both antidepressant medication, specifically SSRIs, and nonpharmacological modalities in treatment plans for severe depression. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for addressing common clinical dilemmas in older individuals. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions. Nonetheless, the guidelines cannot address the complexities involved in the care of each individual patient and can be most helpful in the hands of experienced clinicians.

Aged↗

TE-switched double-contrast enhanced visualization of vascular system and instruments for MR-guided interventions.

A visualization principle for MR-guided vascular interventions based on the concerted use of two contrast agents is introduced. The first contrast agent, consisting of small paramagnetic iron oxide particles, was administered intravenously to shorten T(1), and even more so T *(2), of the blood for extended time periods. The second agent, a monomeric gadolinium complex, was added to a solution in an interventional device, such as a percutaneous-transluminal-angioplasty (PTA) balloon, to reduce T(1) with only minor additional effects on T *(2). With appropriate T(1)- and T *(2)-weighting the vascular tree (TE <3 ms) and the device (TE > or =8 ms) could be selectively imaged (TR <20 ms). Potentially, both images could be simultaneously updated in the subsecond range. Whereas a visualization of thin structures like guidewires was found to require pulse-sequence optimization, a successful visualization of a PTA balloon in a swine aorta in vivo was possible with standard sequences.

Angioplasty, Balloon, Coronary↗

Regulation of meiotic recombination and prophase I progression in mammals.

Meiosis is the process by which diploid germ cells divide to produce haploid gametes for sexual reproduction. The process is highly conserved in eukaryotes, however the recent availability of mouse models for meiotic recombination has revealed surprising regulatory differences between simple unicellular organisms and those with increasingly complex genomes. Moreover, in these higher eukaryotes, the intervention of physiological and sex-specific factors may also influence how meiotic recombination and progression are monitored and regulated. This review will focus on the recent studies involving mouse mutants for meiosis, and will highlight important differences between traditional model systems for meiosis (such as yeast) and those involving more complex cellular, physiological and genetic criteria.

Animals↗

Immune complexes present in the sera of autoimmune mice activate rheumatoid factor B cells.

The fate of an autoreactive B cell is determined in part by the nature of the interaction of the B cell receptor with its autoantigen. In the lpr model of systemic autoimmunity, as well as in certain human diseases, autoreactive B cells expressing rheumatoid factor (RF) binding activity are prominent. A murine B cell transgenic model in which the B cell receptor is a RF that recognizes IgG2a of the j allotype (IgG2aj), but not the b allotype, was used in this study to investigate how the form of the autoantigen influences its ability to activate B cells. We found that sera from autoimmune mice, but not from nonautoimmune mice, were able to induce the proliferation of these RF+ B cells but did not stimulate B cells from RF- littermate controls. The stimulatory factor in serum was found to be IgG2aj, but the IgG2aj was stimulatory only when in the form of immune complexes. Monomeric IgG2aj failed to stimulate. Immune complexes containing lupus-associated nuclear and cytoplasmic autoantigens were particularly potent B cell activators in this system. Appropriate manipulation of such autoantibody/autoantigen complexes may eventually provide a means for therapeutic intervention in patients with certain systemic autoimmune disorders.

Animals↗

An ecosystem approach to malaria control in an urban setting.

We conducted a research project aimed at strengthening local government and the community for a sustainable malaria control strategy. The project began with a baseline diagnosis of malaria prevalence, a KAP survey, entomology, and health services delivery, after which an epidemiological study was performed to identify risk factors associated with malaria, thereafter used to plan intervention measures. A program evaluation was conducted five years later. By using an ecosystem approach to reanalyze data, this paper discusses how malaria arises from a complex interaction of cultural, economic, ecological, social, and individual factors. Intervention measures require an intersectorial and transdisciplinary approach that does not exist at the moment. Health sector leadership is limited, and there is no true community participation. Implications for research, including the use of qualitative and quantitative methods, study design, and complexity of data analysis are discussed. Finally, implications for malaria control are discussed, stressing the differences between the ecosystem and integrated disease control approaches.

Animals↗

[Cardiac catheterization in neonates: experience in 26 neonates].

Cardiac catheterization is rarely performed in neonates in China. The medical records of 26 neonates who underwent cardiac catheterization in Shanghai Children's Medical Center from June 1994 to June 2004 were reviewed. These infants weighed 2300 to 4500 g (mean 3 400 +/- 500 g). Postnatal age ranged from 5 to 28 days (mean 15.2 +/- 8.7 days). Right heart ventricle angiography was performed in 24 cases, left heart ventricle angiography in 20 cases and pulmonary angiography in 6 cases. Balloon aortic septostomy (BAS) was performed in 10 cases. Twenty cases were diagnosed with complex cyanotic cardiovascular malformations and 4 with acyanotic heart disease. The implantation of a temporary cardiac pacemaker was performed in 2 cases. All diagnostic and interventional procedures were successfully performed. The catheterization-related complications occurred in 15.3% of the 26 cases, but without mortality. In conclusion, cardiac catheterization is an accurate and safe method for diagnosing complex congenital heart diseases in neonates. Interventional catheterization is useful in the treatment of complex congenital heart malformations.

Cardiac Catheterization↗

Ineffective breathing pattern related to malnutrition.

This article has highlighted the problem of malnutrition in the stable COPD patient and the critically ill, hypercatabolic patient, and has reviewed resultant mechanisms which influence the alteration of breathing pattern. These complex patients present a challenge for the nurse. Table 1 briefly summarizes the manifestations of malnutrition, goals, interventions and expected outcomes of the nursing diagnosis, ineffective breathing pattern related to malnutrition. The goal of the interventions is to modify the cause (malnutrition) of the nursing diagnosis (altered breathing pattern). The success of the interventions will lead to the achievement of expected outcome As expected outcomes are achieved, relief of signs and symptoms related to the nursing diagnosis will occur. The nurse caring for the patient with actual or potential malnutrition must be knowledgeable about the physiology of malnutrition and effect on breathing pattern. It is essential that the nurse assess and provide appropriate nutritional support and evaluate progress toward expected outcomes. In the event that expected outcomes are not achieved, reassessment with modification of interventions is necessary. Nurses play a key role in the total health care delivery to these complex patients. Further study will strengthen the research base of nursing interventions.

Anthropometry↗

The effect of a social support boosting intervention on stress, coping, and social support in caregivers of children with HIV/AIDS.

BACKGROUND: Caring for the human immunodeficiency virus (HIV)-infected child is challenging and affects the entire family system. Studies have shown that social support can mitigate caregiver stress and enhance coping; however, social support may not always result in a positive outcome for the recipient. OBJECTIVES: To measure caregiver stress, coping, and social support, and to test the effect of a social support boosting intervention on levels of stress, coping, and social support among caregivers of children with HIV/acquired immune deficiency syndrome (AIDS). METHODS: An experimental design was used with monthly social support boosting interventions implemented. The stratified randomized sample included 70 primary caregivers of children with HIV/AIDS. The sample strata were seropositive caregivers (biological parents) and seronegative caregivers (foster parents and extended family members). Study measures included the Derogatis Stress Profile, Family Crisis Oriented Personal Evaluation Scale, and the Tilden Interpersonal Relationship Inventory. Data were analyzed using descriptive statistics and repeated measure MANOVA. RESULTS: Statistically significant differences between the experimental and control groups were found on changes in the dependent variables over time when caregiver strata were included as a factor in the analysis; no statistically significant results were found when caregiver strata were combined. Univariate Ftests indicated that the level of social support for caregivers who were seronegative in the experimental group was significantly different from seronegative caregivers in the control group and seropositive caregivers in both groups. No significant treatment group differences were found for seropositive caregivers. CONCLUSIONS: Seronegative caregivers derived substantial benefit from the social support boosting intervention. Seronegative caregivers who acquire a child with HIV/AIDS are confronted with a complex stressful situation; the critical need to enhance their social support is achievable through the intervention tested in this study.

Adaptation, Psychological↗