Vagal heart rate control in patients with atrial fibrillation: impact of tonic activation of peripheral chemosensory function in heart failure.

Heart failure (HF) and atrial fibrillation (AF), emerging as two epidemics of the twenty-first century, are commonly associated with each other. Both have been mechanistically linked to changes in cardiac vagal control. The importance of peripheral chemosensors, located in the carotid body, has not been elucidated so far. We therefore investigated whether tonic activation of excitatory chemoreceptor afferents contributes to the altered vagal control in HF patients with a history of AF. In 18 patients (72 ±9 year, 7 male) with sinus rhythm and a history of AF (n=9, without any evidence of structural heart disease, AF group; n=9 with structural heart disease and clinical presentation of HF, AFHF group) we investigated the impact of chemosensory deactivation (by breathing 100% oxygen) on heart rate, blood pressure, cardiac output, total peripheral resistance, oxygen saturation and breathing rate. Ten healthy individuals served as a control group. In addition, we performed a deep breathing test demonstrating an impaired heart rate variation in patients with and without HF as compared with controls (expiration/inspiration difference: 23.9±6.9 vs. 6.9±6.1 bpm, and 23.9±6.9 vs. 7.8±4.8 bpm; p<0.05). In both control and AF groups, heart rate decreased during chemoreceptor deactivation (control: -4.8±3.4%; AF: -5.1±3.0%; p<0.05), whereas heart rate did not change in AFHF patients. This resulted in impaired cardiac chemoreflex sensitivity in AFHF patients (1.9±1.6 vs. 0.5±1.2 ms/mmHg; p<0.05). In conclusion, our data suggest that tonic activation of excitatory chemoreceptor afferents contributes to a low vagal tone in heart failure patients with a history of AF (Clinical Trials NCT01262508).

Ventricular tachycardia and sudden death after primary PCI-reperfusion therapy: impact on primary prevention of sudden cardiac death.

BACKGROUND: Current approaches to coronary artery disease (CAD) and acute myocardial infarction (MI) may not be well represented in most primary prevention trials of sudden cardiac death (SCD). METHODS: The contemporary and ongoing registry of the Rostock infarction network (Drip & Ship) represents a well-defined cohort of patients subjected to percutaneous coronary intervention (PCI) for ST-elevation infarction (STEMI) and served as the database for both candidates for an ICD for primary prevention of SCD and for sudden death (SCD) or ventricular tachycardia (VT) during follow-up. RESULTS: A total of 855 consecutive patients were treated with PCI for STEMI or NSTEMI in the region of Rostock (Germany) between 2001 and 2004. While all cause mortality was still 17.2%, the SCD rate was low at 1.3% during 728 ± 366 days of follow-up. Within that time 85 patients (9.9%) developed an indication for ICD therapy due to an impaired LV function (LVEF ≤ 35%) and heart failure. Univariate predictors of an ICD indication were delayed reperfusion (p = 0.001), a high creatine kinase (CK) max (p = 0.009), a persistent wide QRS complex (p = 0.001), previous cerebrovascular events (p = 0.033), and chronic renal failure (p = 0. 001). However, only 16.5% of these patients qualifying for an ICD actually received an ICD; nevertheless, the actual SCD rate was only 3.5%, while 5.4% (46 patients) suffered VTs or ventricular fibrillation (VF). The SCD/VT rate in the entire infarct population was associated with time to reperfusion (0.032), left bundle-branch block (0.002), a longer history of CAD (0.032), and VT during follow-up. CONCLUSION: While mortality in patients with STEMI is still alarming even with PCI, the risk of SCD may be considerably decreased even in patients with an LVEF below 35%. With the current approach to primary prevention of sudden cardiac death, approximately 10% of postinfarction patients qualify for ICD therapy; however this may only reach a quarter of patients prone to SCD.

[Positive influence on cardiovascular risk factor by blocking the endocannabinoid system]. / Positive Beeinflussung kardiovaskulärer Risikofaktoren durch Blockade des Endocannabinoidsystems.

Intra-abdominal fat mass, or central adiposity, and cardiovascular risk are strongly correlated. Adipose tissue is an endocrine organ that secretes hormones and cytokines influencing appetite, energy metabolism, and atherosclerosis. Rimonabant is the first selective blocker of the cannabinoid-1 receptor in development for the treatment of obesity, diabetes mellitus typ 2, and cardiometabolic risk factors. This article provides an review of efficacy of rimonabant the first selective blocker of the cannabinoid-1 receptor.

[Life experience of adults with unilateral agenesia of the forearm: effect of prosthesis on self image and social relations]. / Parcours de vie d'adultes présentant une agénésie unilatérale d'avant-bras: enjeux et incidence du recours à la prothèse sur l'image de soi et les relations sociales.

PURPOSE OF THE STUDY: This study was devoted to better understanding how adults with agenesia of the forearm live their condition. The malformation studied was identical to that of a previous study in children. The present study was designed to provide professionals and parents with a reference system for making therapeutic decisions. MATERIAL AND METHODS: An intensive survey using semi-directive interviews was conducted among adults aged 19 to 37 years, 12 women and 8 men, with unilateral agenesia of the forearm. The majority of the participants had an occupation and an active social and familial life. RESULTS: The survey revealed factors of limitation or progress, expectations and renouncements, marking the life experience of these persons. The prosthesis had a significant impact on their lives. DISCUSSION: Four types of life experience could be identified from the survey data. All four could be understood as a search for equilibrium between internal reality (desired self image) and external reality (image produced by the physical and human environment via the regards of others and obstacles encountered). Several modalities for using a prosthesis, several ways of coping with the absence of a hand, with or without a prosthesis, and several ways of constructing a self-representation were distinguished. Rather than a functional disability, agenesia was found to be perceived as a persistent problem in daily life, generating handicap- or discrimination-producing situations. CONCLUSION: Forearm agenesia creates a situation different from normal and as such makes the question of self-identity and social relations more complex than for others. The comments provided by these young adults who cope with the paradoxical condition of an amputated but functional body demonstrated the central role of the body.

Enrolling research subjects from clinical practice: ethical and procedural issues in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is a multi-site effectiveness study funded by the National Institute of Mental Health (NIMH) with the aim of identifying successful, acceptable and cost-effective treatment strategies for outpatients with unremitted depression. With enrollment of 4,041 adults with major depressive disorder (MDD), it is the largest controlled psychiatric treatment study ever undertaken. In the course of developing procedures to ensure that ambitious enrollment goals were met, a number of ethical and practical issues became apparent that underscore the conflicts between effectiveness research and human subject protections. These are delineated as they relate to study design; eligibility criteria; incentives to subjects; investigators and clinical sites; the complementary roles of clinical research coordinators (CRCs) and study clinicians; and recruitment and consent procedures. The STAR*D trial exemplifies the interplay and tension between those strategies that integrate research and clinical aims and roles in the service of enhancing external validity, site participation, and recruitment and retention versus those strategies that differentiate research and clinical treatment in the service of research integrity and human subject protections. We hope that a discussion of these key challenges and dilemmas and how they have been addressed will help inform future discussions concerning design and conduct of ethical effectiveness trials designed to optimize care in real world clinical settings.

Percutaneous transcatheter closure of patent foramen ovale.

In presence of a patent foramen ovale (PFO) with cryptogenic cerebral embolism, traditional therapy consists of oral anticoagulation or antiplatelet therapy. Surgery was considered only in case of recurrence. Transcatheter closure of PFO is currently performed. The availability of new user friendly devices and the increasing knowledge of pathophysiology, epidemiology, and follow-up of these patients has broadened the indications and marked reduced morbidity related to interventional PFO closure. This review presents the current knowledge and our own data concerning transcatheter closure of PFO.

Initiation of hypertension treatment with a fixed-dose combination or its monocomponents -- does it really matter?

Despite efforts to diagnose and treat hypertension effectively, the goal of lowering blood pressure (BP) levels is rarely achieved, as treatment is often initiated with a single antihypertensive agent. The aim of this study was to assess the safety and efficacy of a first-line fixed-dose combination treatment compared with treatment with its monocomponents over a period of 4 weeks. Patients (n = 149) with essential hypertension were randomised to receive 2.5 mg of either ramipril or felodipine ER or the fixed-dose combination of ramipril 2.5 mg/felodipine ER 2.5 mg over a 4-week treatment period. BP and heart rate were measured by conventional methodology and 24-hour ambulatory blood pressure measurements. Treatment with the fixed-dose combination was significantly more effective in reducing systolic and diastolic BP (-15.8/-9.2 mmHg) compared with its monocomponents, ramipril (-7.6/-3.8 mmHg) and felodipine ER (-8.0/-5.0 mmHg). No significant difference could be observed in the occurrence of a greater fall in systolic and diastolic BP 6 h after the first dose of the three study medications. The adverse effects reported were mild, and less number of patients in the fixed-dose combination complained of adverse events. It can be concluded that initiating antihypertensive treatment with a low fixed-dose combination of ramipril/felodipine ER is more effective and safe when compared with treatment with its monocomponents.

Methods of testing feasibility for sequenced treatment alternatives to relieve depression (STAR*D).

In large multi-site trials, a feasibility or pilot study can be crucial to test the functionality of all aspects of conducting the study prior to the initiation of the formal study. A feasibility trial was conducted for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Project, a multi-site, prospective, sequentially randomized, clinical trial of outpatients with nonpsychotic major depressive disorder. From 14 December 2000 to 8 June 2001, 42 patients were screened for enrollment into the STAR*D Feasibility Trial. Twenty-four patients who were eligible and consented to participate were treated with citalopram for up to 12 weeks. During the course of this trial, issues were raised that resulted in modifications to the study procedures. Modifications made as a result of this trial affected four domains: (1) communication, (2) patient and provider burden, (3) data collection forms, and (4) recruitment and retention of subjects. This paper describes what was learned during the STAR*D Feasibility Trial so researchers planning to conduct similar trials can learn the practical issues related to conducting such a research project. While the information gathered was useful, it did delay the initiation of the formal trial. We view this cost as an investment in the development of overall study procedures that should lead to a stronger study.

[Wishes of nursing home residents concerning their life situation--results of a qualitative study]. / "Pflege mit Herz, Gesundheit oder Sterben"--Wünsche zur Veränderung der Lebenssituation von Altenpflegeheimbewohnern.

OBJECTIVE: This study examined the wishes of nursing home residents concerning their life situation in the nursing home. METHODS: Using a qualitative study design, a representative sample of nursing home residents (n = 1656) of 24 nursing homes in a city situated in the eastern part of Germany were interviewed. RESULTS: The analyses of residents' wishes lead to major domains such as the quality of care, interpersonal contact, architecture and organization of the house, diversification, financial support, as well as themes like health and death and the wish to leave the nursing home. Residents focus on an individualized approach to care. CONCLUSIONS: Nursing home residents' views support the need to improve the psychological and social aspects of the quality of care. Implications of and consequences for the organization of care and concepts of nursing are discussed.

[Unilateral forearm agenesis and prosthesis]. / Agénésie unilatérale d'avant-bras et prothétisation.

PURPOSE OF THE STUDY: Antebrachial agenesis is a congenital deformity which is not invalidating for the children who have a level of independence comparable to that of other children of the same age. Although the appropriateness of a prosthesis is rarely questioned by healthcarers, it is clear that it is the healthcarers' own representation of this condition (their knowledge of the deformity and of the prosthesis proposed) that leads to the indication. The purpose of this study was to better understand the respective representations of unilateral antebrachial agenesis to help determine appropriate health care proposals. MATERIAL AND METHODS: An intensive survey using semi-directive interviews was conducted in 16 families. Group interviews with three healthcare teams were then conducted. RESULTS: Three leading topics appeared: worry about the social integration of the child, a paradoxical representation of the child perceived as independent but handicapped, and a largely negative image of the prosthesis. There was a rather important difference in the representations formulated by the parents and by the healthcarers. DISCUSSION: The discussion focused on awareness of the narcissistic content of the expectations and the plastic and functional implications of prosthesis fitting, perceived differently by parents and healthcarers. CONCLUSION: The nature of the expected result involves a change in the representation of the child more than a change in the child's body, a concept which in itself is not a true objective of healthcare. Taken the understandably difficult position of healthcarers, it might be useful to propose a different scheme for the first consultation.

Children's spatial behavior is differentially affected after traumatic brain injury.

Spatial behavior in 20 children with severe traumatic brain injury (TBI) and 20 healthy controls was investigated using the Kiel Locomotor Maze. Children had to remember defined locations in an experimental chamber with completely controlled intra- and extra-maze cues until learning criterion was reached. In a second experiment, spatial orientation strategies were assessed. Children with TBI were shown to be impaired in spatial learning and spatial memory. Spatial orientation was found to be deficient even in cases where spatial learning and memory proved to be unimpaired, especially in tasks that demanded the use of relational place strategies. Children who suffered a TBI at an early age proved to be more severely impaired in spatial learning and orientation than older children.

[Stage-oriented nursing care rates in neurologic rehabilitation]. / Stadienorientierte Pflegesatzfindung in der neurologischen Rehabilitation.

The aim of this pilot study done in a neurological rehabilitation center for children and adolescents was to increase the transparency of costs in relation to work and to gain differentiated daily rates according to the kind and amount of nursing and multidisciplinary treatment of patients in different phases (B, C, D) of neurorehabilitation. Presented and discussed are methods and instruments for performance registration and connecting them to costs. As the study shows quite different daily rates are necessary to assure adequate treatment for young patients in different phases--early to late--of neurological rehabilitation.

High prevalence of CACNA1A truncations and broader clinical spectrum in episodic ataxia type 2.

OBJECTIVE: To characterize the nature of CACNA1A mutations in episodic ataxia type 2 (EA2), to search for mutations in sporadic cases, and to delineate better the clinical spectrum. BACKGROUND: EA2 is an autosomal dominant disorder characterized by recurrent acetazolamide-responsive attacks of cerebellar ataxia. The mutated gene, CACNA1A, located on chromosome 19, encodes the alpha1A subunit of a voltage-dependent calcium channel. So far, only three CACNA1A mutations have been identified-in two EA2 families and in one sporadic case. These three mutations disrupted the reading frame and led to truncated proteins. Interestingly, distinct types of CACNA1A mutations have been identified in familial hemiplegic migraine (missense mutations) and spinocerebellar ataxia type 6 (SCA-6) progressive cerebellar ataxia (expanded CAG repeats). However, except for SCA-6, these genotype-phenotype correlations relied on the analysis of very few families. METHODS: To characterize CACNA1A mutations, eight familial and seven sporadic EA2 patients were selected. All 47 exons of CACNA1A were screened by a combination of single-strand conformer polymorphism and sequencing analysis. In addition, the length of the CAG repeat has been determined in all patients. RESULTS: Seven new mutations were detected in four multiple case families and three sporadic cases. Six of them lead most likely to truncated or aberrant proteins. CAG repeat sizes were in the normal range. CONCLUSION: These data clearly establish the specificity of EA2 mutations compared with SCA-6 and familial hemiplegic migraine. Detailed clinical analysis of the mutation carriers showed the highly variable penetrance and expression of this disorder: Several of the carriers did not show any clinical symptom; others displayed atypical or permanent neurologic symptoms (such as recurrent, transient diplopia or severe, permanent, and isolated cerebellar ataxia).

Influence of age-related factors on long-term outcome after traumatic brain injury (TBI) in children: A review of recent literature and some preliminary findings.

Cerebral plasticity of the immature brain is often inferred to lead to less serious consequences of early traumatic brain injury (TBI) in the pediatric age group. This notion is seriously challenged by recent research findings. Data from prospective studies point to some children's dif-ficulties in ongoing skill-acquisition and the possibility of late-emerging deficits. Accordingly, preliminary group data of an own ongoing study support the notion of an increased risk for pervasive neuropsychological impairment in subjects with severe TBI and early age at trauma. The pattern of neuropsychological deficits may depend on the developmental level at the time of injury, although effects of hemispheric site of lesion were also found to persist in individual cases. Theoretical considerations and empirical findings stress the importance of a longitudinal developmental perspective for the evaluation of long-term outcome after pediatric TBI. ("Verbund Neurotrauma Kiel / Project 4: Evaluation of neurological rehabilitation and course of cognitive development in children and adoles-cents with secondarily acquired brain damage", funded through the Research Program "Gesundheit 2000" of the German government, FKZ 01 KO 9512.).

Assessment of sensorimotor functions after traumatic brain injury (TBI) in childhood - Methodological aspects.

Various basic qualitative and quantitative methods for the evaluation of sensorimotor functions after Traumatic Brain Injury (TBI) are introduced and discussed. Methodological aspects are illustrated by a single case follow-up study of a child after severe TBI (age 11; 7–12;1 yrs; 6, 8 and 12 month post TBI) in comparison to an age-matched healthy control group (N=16). The evaluation consisted of neurological investigation, Barthel-Index, Terver Numeric Score for Functional Assessment, Rappaport Disability Rating Scale (modified version), a coordination-test for children (KTK), a pilot-tested Motor Function Score, quantitative evaluation of spatiotemporal gait parameters on a walkway and on a treadmill, and the kinematic assessment of hand motor functions. Quantitative movement analyses revealed two general types of motor disorder: Slowing of movements and compensatory motor strategies. Averaged z-scores showed deficits, which were pronounced in fine motor skills (hand movements: 1.86, gait: 1.3). During follow-up, a strong improvement rate during the first (-0.48 z-scores) and nearly no improvement rate (-0.03 z-scores) during the second time interval was seen. Clinical scores and developmental tests were not able to document the whole restitutional course, whereas motor tests with special emphasis on functional aspects and the quantitative movement assessment seemed to be suitable methods. We conclude that a sufficient evaluation of sensorimotor functions after TBI in childhood needs an increase in procedural uniformity on onehand and the combination of various qualitative and quantitative methods on the other hand. To connect both claims, further research is necessary.

Seroprevalence of human T cell lymphotropic virus type II infection, with or without human immunodeficiency virus type 1 coinfection, among US intravenous drug users.

Seroprevalence of human T lymphotropic virus (HTLV) and human immunodeficiency virus type 1 (HIV-1) was determined among 7841 intravenous drug users (IVDUs) from drug treatment centers in Baltimore, Chicago, Los Angeles, New Jersey (Asbury Park and Trenton), New York City (Brooklyn and Harlem), Philadelphia, and San Antonio, Texas; 20.9% had evidence of HTLV infection, as determined using a p21e EIA for screening and p21e blot for confirmation. With a type-specific EIA and blot used in combination, HTLV-II was identified in 97.6% of HTLV-positive IVDUs whose sera could be subtyped. HIV-1 seroprevalence was 13.2%. HTLV-II without HIV-1 was most common in Los Angeles and San Antonio. HIV-1 without HTLV-II was most common in New York, New Jersey, and Baltimore. Dual infection was most common in New York and New Jersey. Logistic regression analysis revealed that seroprevalence of HTLV-II was significantly greater with HIV-1 infection and increasing age and among women, blacks, and Mexican-Americans. In conclusion, it appears that among US IVDUs, nearly all HTLV infection is attributable to HTLV-II, and HTLV-II infection is associated with HIV-1 and sociodemographic background.

Hospital benefits when managers put their heads together.

To improve its efficiency and effectiveness, Alexandria Hospital, Alexandria, VA, has developed a strategy of participatory management: the management advisory board. The board, made up of 16 middle managers elected for six-month terms, is a problem-solving, idea-generating forum that may get involved in almost any aspect of hospital operations. Project ideas, which must be aimed at increasing the morale, efficiency, and effectiveness of the hospital and employees, can come from any employee at any level. Once a project has been accepted, it is assigned to a project committee, made up of at least three members who are given much latitude and are encouraged to use their individual and group talents and creativity. After the project has been completed and approved by the full board, it is submitted to the administration for approval and implementation. The board's results have led to a number of new policies and programs at the hospital, including "employee-of-the-year" recognition, standardized uniforms, disaster plans, quality circles, and management orientation. The board is now developing a physician orientation program, identifying outpatient service opportunities, investigating ways to control the use of copying machines, and studying the feasibility of using one particular travel agency for hospital travel.

[The locked-in syndrome]. / Le syndrome de verrouillage.

The locked-in syndrome is poorly understood, and may be misdiagnosed as coma. The syndrome consists of complete paralysis of all four limbs and the lower cranial nerve pairs, associated with an unaltered consciousness. Vertical eye movements and blinking remain intact, so allowing some form of communication by way of eye codes. Obstruction of the vertebral and basilar vascular system is the major cause, but the six cases reported show the aetiological diversity of this syndrome. If the vascular obstruction is diagnosed within the first few hours, fibrinolytic therapy may be considered. Although the patients usually die within a few days or after several months, some rare cases of recovery after several weeks have been reported. Intensive care is required by these patients (tracheostomy, artificial ventilation, intensive nursing care); the physicians and nursing staff looking after them should always keep in mind that these patients are conscious and able to communicate.