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1.
BMC Palliat Care ; 22(1): 102, 2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37481524

ABSTRACT

BACKGROUND: In Palliative Care, actors from different professional backgrounds work together and exchange case-specific and expert knowledge and information. Since Palliative Care is traditionally distant from digitalization due to its holistically person-centered approach, there is a lack of suitable concepts enabling digitalization regarding multi-professional team processes. Yet, a digitalised information and collaboration environment geared to the requirements of palliative care and the needs of the members of the multi-professional team might facilitate communication and collaboration processes and improve information and knowledge flows. Taking this chance, the presented three-year project, PALLADiUM, aims to improve the effectiveness of Palliative Care teams by jointly sharing available inter-subjective knowledge and orientation-giving as well as action-guiding practical knowledge. Thus, PALLADiUM will explore the potentials and limitations of digitally supported communication and collaboration solutions. METHODS: PALLADiUM follows an open and iterative mixed methods approach. First, ethnographic methods - participant observations, interviews, and focus groups - aim to explore knowledge and information flow in investigating Palliative Care units as well as the requirements and barriers to digitalization. Second, to extend this body, the analysis of the historical hospital data provides quantitative insights. Condensing all findings results in a to-be work system. Adhering to the work systems transformation method, a technical prototype including artificial intelligence components will enhance the collaborative teamwork in the Palliative Care unit. DISCUSSION: PALLADiUM aims to deliver decisive new insights into the preconditions, processes, and success factors of the digitalization of a medical working environment as well as communication and collaboration processes in multi-professional teams. TRIAL REGISTRATION: The study was registered prospectively at DRKS (Deutsches Register Klinischer Studien) Registration-ID: DRKS0025356 Date of registration: 03.06.21.


Subject(s)
Hospice and Palliative Care Nursing , Palliative Care , Humans , Palladium , Artificial Intelligence , Research Design
2.
BMC Palliat Care ; 22(1): 50, 2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37101258

ABSTRACT

BACKGROUND: Palliative care is an integral part of health care, which in term has become increasingly technologized in recent decades. Lately, innovative smart sensors combined with artificial intelligence promise better diagnosis and treatment. But to date, it is unclear: how are palliative care concepts and their underlying assumptions about humans challenged by smart sensor technologies (SST) and how can care benefit from SST? AIMS: The paper aims to identify changes and challenges in palliative care due to the use of SST. In addition, normative guiding criteria for the use of SST are developed. METHODS: The principle of Total Care used by the European Association for Palliative Care (EAPC) forms the basis for the ethical analysis. Drawing on this, its underlying conceptions of the human and its socio-ethical aspects are examined with a phenomenological focus. In the second step, the advantages, limitations, and socio-ethical challenges of using SST with respect to the Total Care principle are explored. Finally, ethical-normative requirements for the application of SST are derived. RESULTS AND CONCLUSION: First, SST are limited in their measurement capabilities. Second, SST have an impact on human agency and autonomy. This concerns both the patient and the caregiver. Third, some aspects of the Total Care principle are likely to be marginalized due to the use of SST. The paper formulates normative requirements for using SST to serve human flourishing. It unfolds three criteria according to which SST must be aligned: (1) evidence and purposefulness, (2) autonomy, and (3) Total Care.


Subject(s)
Hospice and Palliative Care Nursing , Palliative Care , Humans , Artificial Intelligence , Delivery of Health Care , Technology
3.
Front Digit Health ; 3: 765867, 2021.
Article in English | MEDLINE | ID: mdl-34913047

ABSTRACT

The world of healthcare constantly aims to improve the lives of people while nurturing their health and comfort. Digital health and wearable technologies are aimed at making this possible. However, there are numerous factors that need to be addressed such as aging, disabilities, and health hazards. These factors are intensified in palliative care (PC) patients and limited hospital capacities make it challenging for health care providers (HCP) to handle the crisis. One of the most common symptoms reported by PC patients with severe conditions is dyspnoea. Monitoring devices with sufficient comfort could improve symptom control of patients with dyspnoea in PC. In this article, we discuss the proof-of-concept study to investigate a smart patch (SP), which monitors the pulmonary parameters: (a) breathing rate (BR) and inspiration to expiration ratio (I:E); markers for distress: (b) heart rate (HR) and heart rate variability (HRV), and (c) transmits real-time data securely to an adaptable user interface, primarily geared for palliative HCP but scalable to specific needs. The concept is verified by measuring and analyzing physiological signals from different electrode positions on the chest and comparing the results achieved with the gold standard Task Force Monitor (TFM).

4.
Front Digit Health ; 3: 724049, 2021.
Article in English | MEDLINE | ID: mdl-34713190

ABSTRACT

We propose a novel knowledge extraction method based on Bayesian-inspired association rule mining to classify anxiety in heterogeneous, routinely collected data from 9,924 palliative patients. The method extracts association rules mined using lift and local support as selection criteria. The extracted rules are used to assess the maximum evidence supporting and rejecting anxiety for each patient in the test set. We evaluated the predictive accuracy by calculating the area under the receiver operating characteristic curve (AUC). The evaluation produced an AUC of 0.89 and a set of 55 atomic rules with one item in the premise and the conclusion, respectively. The selected rules include variables like pain, nausea, and various medications. Our method outperforms the previous state of the art (AUC = 0.72). We analyzed the relevance and novelty of the mined rules. Palliative experts were asked about the correlation between variables in the data set and anxiety. By comparing expert answers with the retrieved rules, we grouped rules into expected and unexpected ones and found several rules for which experts' opinions and the data-backed rules differ, most notably with the patients' sex. The proposed method offers a novel way to predict anxiety in palliative settings using routinely collected data with an explainable and effective model based on Bayesian-inspired association rule mining. The extracted rules give further insight into potential knowledge gaps in the palliative care field.

5.
Sci Rep ; 11(1): 3025, 2021 02 04.
Article in English | MEDLINE | ID: mdl-33542260

ABSTRACT

Contactless measurement of heart rate variability (HRV), which reflects changes of the autonomic nervous system (ANS) and provides crucial information on the health status of a person, would provide great benefits for both patients and doctors during prevention and aftercare. However, gold standard devices to record the HRV, such as the electrocardiograph, have the common disadvantage that they need permanent skin contact with the patient. Being connected to a monitoring device by cable reduces the mobility, comfort, and compliance by patients. Here, we present a contactless approach using a 24 GHz Six-Port-based radar system and an LSTM network for radar heart sound segmentation. The best scores are obtained using a two-layer bidirectional LSTM architecture. To verify the performance of the proposed system not only in a static measurement scenario but also during a dynamic change of HRV parameters, a stimulation of the ANS through a cold pressor test is integrated in the study design. A total of 638 minutes of data is gathered from 25 test subjects and is analysed extensively. High F-scores of over 95% are achieved for heartbeat detection. HRV indices such as HF norm are extracted with relative errors around 5%. Our proposed approach is capable to perform contactless and convenient HRV monitoring and is therefore suitable for long-term recordings in clinical environments and home-care scenarios.


Subject(s)
Autonomic Nervous System/physiology , Heart Rate/physiology , Heart Sounds/physiology , Monitoring, Physiologic/methods , Adult , Autonomic Nervous System/diagnostic imaging , Electrocardiography/instrumentation , Female , Humans , Interferometry/instrumentation , Male , Monitoring, Physiologic/instrumentation , Radar/instrumentation
6.
Sci Data ; 7(1): 291, 2020 09 08.
Article in English | MEDLINE | ID: mdl-32901032

ABSTRACT

Using Radar it is possible to measure vital signs through clothing or a mattress from the distance. This allows for a very comfortable way of continuous monitoring in hospitals or home environments. The dataset presented in this article consists of 24 h of synchronised data from a radar and a reference device. The implemented continuous wave radar system is based on the Six-Port technology and operates at 24 GHz in the ISM band. The reference device simultaneously measures electrocardiogram, impedance cardiogram and non-invasive continuous blood pressure. 30 healthy subjects were measured by physicians according to a predefined protocol. The radar was focused on the chest while the subjects were lying on a tilt table wired to the reference monitoring device. In this manner five scenarios were conducted, the majority of them aimed to trigger hemodynamics and the autonomic nervous system of the subjects. Using the database, algorithms for respiratory or cardiovascular analysis can be developed and a better understanding of the characteristics of the radar-recorded vital signs can be gained.


Subject(s)
Monitoring, Ambulatory/instrumentation , Radar , Vital Signs , Algorithms , Autonomic Nervous System , Healthy Volunteers , Hemodynamics , Humans
7.
Sci Data ; 7(1): 50, 2020 02 13.
Article in English | MEDLINE | ID: mdl-32054854

ABSTRACT

Radar systems allow for contactless measurements of vital signs such as heart sounds, the pulse signal, and respiration. This approach is able to tackle crucial disadvantages of state-of-the-art monitoring devices such as the need for permanent wiring and skin contact. Potential applications include the employment in a hospital environment but also in home care or passenger vehicles. This dataset consists of synchronised data which are acquired using a Six-Port-based radar system operating at 24 GHz, a digital stethoscope, an ECG, and a respiration sensor. 11 test subjects were measured in different defined scenarios and at several measurement positions such as at the carotid, the back, and several frontal positions on the thorax. Overall, around 223 minutes of data were acquired at scenarios such as breath-holding, post-exercise measurements, and while speaking. The presented dataset contains reference-labeled ECG signals and can therefore easily be used to either test algorithms for monitoring the heart rate, but also to gain insights about characteristic effects of radar-based vital sign monitoring.


Subject(s)
Heart Sounds , Radar , Signal Processing, Computer-Assisted , Vital Signs , Algorithms , Heart Rate , Humans , Respiration
8.
IEEE Trans Biomed Eng ; 67(3): 773-785, 2020 03.
Article in English | MEDLINE | ID: mdl-31180834

ABSTRACT

OBJECTIVE: Radar technology promises to be a touchless and thereby burden-free method for continuous heart sound monitoring, which can be used to detect cardiovascular diseases. However, the first and most crucial step is to differentiate between high- and low-quality segments in a recording to assess their suitability for a subsequent automated analysis. This paper gives a comprehensive study on this task and first addresses the specific characteristics of radar-recorded heart sound signals. METHODS: To gather heart sound signals recorded from radar, a bistatic radar system was built and installed at the university hospital. Under medical supervision, heart sound data were recorded from 30 healthy test subjects. The signals were segmented and labeled as high- or low-quality by a medical expert. Different state-of-the-art pattern classification algorithms were evaluated for the task of automated signal quality determination and the most promising one was optimized and evaluated using leave-one-subject-out cross validation. RESULTS: The proposed classifier is able to achieve an accuracy of up to 96.36% and demonstrates a superior classification performance compared with the state-of-the-art classifier with a maximum accuracy of 76.00%. CONCLUSION: This paper introduces an ensemble classifier that is able to perform automated signal quality determination of radar-recorded heart sound signals with a high accuracy. SIGNIFICANCE: Besides achieving a higher performance compared with state-of-the-art classifiers, this study is the first one to deal with the quality determination of heart sounds that are recorded by radar systems. The proposed method enables contactless and continuous heart sound monitoring for the detection of cardiovascular diseases.


Subject(s)
Heart Sounds/physiology , Monitoring, Physiologic/methods , Phonocardiography/methods , Radar/instrumentation , Signal Processing, Computer-Assisted , Adult , Algorithms , Electrocardiography , Equipment Design , Female , Humans , Male , Middle Aged , Phonocardiography/instrumentation , Young Adult
9.
Sensors (Basel) ; 19(11)2019 May 31.
Article in English | MEDLINE | ID: mdl-31159218

ABSTRACT

Vital parameters are key indicators for the assessment of health. Conventional methods rely on direct contact with the patients' skin and can hence cause discomfort and reduce autonomy. This article presents a bistatic 24 GHz radar system based on an interferometric six-port architecture and features a precision of 1 µm in distance measurements. Placed at a distance of 40 cm in front of the human chest, it detects vibrations containing respiratory movements, pulse waves and heart sounds. For the extraction of the respiration rate, time-domain approaches like autocorrelation, peaksearch and zero crossing rate are compared to the Fourier transform, while template matching and a hidden semi-Markov model are utilized for the detection of the heart rate from sphygmograms and heart sounds. A medical study with 30 healthy volunteers was conducted to collect 5.5 h of data, where impedance cardiogram and electrocardiogram were used as gold standard for synchronously recording respiration and heart rate, respectively. A low root mean square error for the breathing rate (0.828 BrPM) and a high overall F1 score for heartbeat detection (93.14%) could be achieved using the proposed radar system and signal processing.


Subject(s)
Biosensing Techniques/methods , Algorithms , Cardiography, Impedance , Electrocardiography , Healthy Volunteers , Heart Rate/physiology , Humans , Markov Chains , Signal Processing, Computer-Assisted
10.
Front Neurol ; 10: 164, 2019.
Article in English | MEDLINE | ID: mdl-30894836

ABSTRACT

Stroke is a leading cause of death, disability and is a symptom burden worldwide. It impacts patients and their families in various ways, including physical, emotional, social, and spiritual aspects. As stroke is potentially lethal and causes severe symptom burden, a palliative care (PC) approach is indicated in accordance with the definition of PC published by the WHO in 2002. Stroke patients can benefit from a structured approach to palliative care needs (PCN) and the amelioration of symptom burden. Stroke outcome is uncertain and outlook may change rapidly. Regarding these challenges, core competencies of PC include the critical appraisal of various treatment options, and openly and respectfully discussing therapeutic goals with patients, families, and caregivers. Nevertheless, PC in stroke has to date mainly been restricted to short care periods for dying patients after life-limiting complications. There is currently no integrated concept for PC in stroke care addressing the appropriate moment to initiate PC for stroke patients, and the question of how to screen for symptoms remains unanswered. Therefore, PC for stroke patients is often perceived as a stopgap in cases of unfavorable prognosis and very short survival times. In contrast, PC can provide much more for stroke patients and support a holistic approach, improve quality of life and ensure treatment according to the patient's wishes and values. In this short review we identify key aspects of PC in stroke care and current barriers to implementation. Additionally, we provide insights into our approach to PC in stroke care.

11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 6677-6680, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31947373

ABSTRACT

Sounds caused by the action of the heart reflect both its health as well as deficiencies and are examined by physicians since antiquity. Pathologies of the valves, e.g. insufficiencies and stenosis, cardiac effusion, arrhythmia, inflammation of the surrounding tissue and other diagnosis can be reached by experienced physicians. However, practice is needed to assess the findings correctly. Furthermore, stethoscopes do not allow for long-term monitoring of a patient. Recently, radar technology has shown the ability to perform continuous touchless and thereby burden-free heart sound measurements. In order to perform automated classification of the signals, the first and most important step is to segment the heart sounds into their physiological phases. This paper examines the use of different Long Short-Term Memory (LSTM) architectures for this purpose based on a large dataset of radar-recorded heart sounds gathered from 30 different test persons in a clinical study. The best-performing network, a bidirectional LSTM, achieves a sample-wise accuracy of 93.4 % and a F1 score for the first heart sound of 95.8 %.


Subject(s)
Heart Sounds , Stethoscopes , Arrhythmias, Cardiac , Heart , Humans , Radar
12.
Sci Rep ; 8(1): 11551, 2018 07 26.
Article in English | MEDLINE | ID: mdl-30068983

ABSTRACT

This paper introduces heart sound detection by radar systems, which enables touch-free and continuous monitoring of heart sounds. The proposed measurement principle entails two enhancements in modern vital sign monitoring. First, common touch-based auscultation with a phonocardiograph can be simplified by using biomedical radar systems. Second, detecting heart sounds offers a further feasibility in radar-based heartbeat monitoring. To analyse the performance of the proposed measurement principle, 9930 seconds of eleven persons-under-tests' vital signs were acquired and stored in a database using multiple, synchronised sensors: a continuous wave radar system, a phonocardiograph (PCG), an electrocardiograph (ECG), and a temperature-based respiration sensor. A hidden semi-Markov model is utilised to detect the heart sounds in the phonocardiograph and radar data and additionally, an advanced template matching (ATM) algorithm is used for state-of-the-art radar-based heartbeat detection. The feasibility of the proposed measurement principle is shown by a morphology analysis between the data acquired by radar and PCG for the dominant heart sounds S1 and S2: The correlation is 82.97 ± 11.15% for 5274 used occurrences of S1 and 80.72 ± 12.16% for 5277 used occurrences of S2. The performance of the proposed detection method is evaluated by comparing the F-scores for radar and PCG-based heart sound detection with ECG as reference: Achieving an F1 value of 92.22 ± 2.07%, the radar system approximates the score of 94.15 ± 1.61% for the PCG. The accuracy regarding the detection timing of heartbeat occurrences is analysed by means of the root-mean-square error: In comparison to the ATM algorithm (144.9 ms) and the PCG-based variant (59.4 ms), the proposed method has the lowest error value (44.2 ms). Based on these results, utilising the detected heart sounds considerably improves radar-based heartbeat monitoring, while the achieved performance is also competitive to phonocardiography.


Subject(s)
Heart Sounds/physiology , Heart/physiology , Monitoring, Physiologic/methods , Radar , Vital Signs/physiology , Algorithms , Biophysical Phenomena , Computer Simulation , Electrocardiography , Heart Rate , Humans , Markov Chains , Models, Theoretical , Phonocardiography , Respiration , Signal Processing, Computer-Assisted
13.
Front Neurosci ; 10: 77, 2016.
Article in English | MEDLINE | ID: mdl-27013940

ABSTRACT

While adult neurogenesis is considered to be restricted to the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ), recent studies in humans and rodents provide evidence for newly generated neurons in regions generally considered as non-neurogenic, e.g., the striatum. Stimulating dopaminergic neurotransmission has the potential to enhance adult neurogenesis in the SVZ and the DG most likely via D2/D3 dopamine (DA) receptors. Here, we investigated the effect of two distinct preferential D2/D3 DA agonists, Pramipexole (PPX), and Ropinirole (ROP), on adult neurogenesis in the hippocampus and striatum of adult naïve mice. To determine newly generated cells in the DG incorporating 5-bromo-2'-deoxyuridine (BrdU) a proliferation paradigm was performed in which two BrdU injections (100 mg/kg) were applied intraperitoneally within 12 h after a 14-days-DA agonist treatment. Interestingly, PPX, but not ROP significantly enhanced the proliferation in the DG by 42% compared to phosphate buffered saline (PBS)-injected control mice. To analyze the proportion of newly generated cells differentiating into mature neurons, we quantified cells co-expressing BrdU and Neuronal Nuclei (NeuN) 32 days after the last of five BrdU injections (50 mg/kg) applied at the beginning of 14-days DA agonist or PBS administration. Again, PPX only enhanced neurogenesis in the DG significantly compared to ROP- and PBS-injected mice. Moreover, we explored the pro-neurogenic effect of both DA agonists in the striatum by quantifying neuroblasts expressing doublecortin (DCX) in the entire striatum, as well as in the dorsal and ventral sub-regions separately. We observed a significantly higher number of DCX(+) neuroblasts in the dorsal compared to the ventral sub-region of the striatum in PPX-injected mice. These results suggest that the stimulation of hippocampal and dorsal striatal neurogenesis may be up-regulated by PPX. The increased generation of neural cells, both in constitutively active and quiescent neurogenic niches, might be related to the proportional higher D3 receptor affinity of PPX, non-dopaminergic effects of PPX, or altered motor behavior.

14.
Curr Opin Support Palliat Care ; 7(4): 417-23, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24152975

ABSTRACT

PURPOSE OF REVIEW: Patients with brain tumours show a high symptom burden, and symptoms are difficult to treat and prone to be overlooked. This review of publications dealing with advanced stages of brain tumours tries to assess the knowledge gained in the past 2 years and to develop an outlook for further investigations. RECENT FINDINGS: We searched for publications on advanced brain tumours in a palliative medicine setting. Of 138 publications retrieved by search in PubMed, 22 publications met our criteria for inclusion. We predefined categories of interest: epidemiology and treatment of symptoms; quality of life; and impact on next of kin, caregivers, medico-social system and decision-making. SUMMARY: Data suggest that patients with primary or metastatic brain tumours often have a high symptom burden and unmet needs for palliative care, and symptoms are hard to diagnose; patients suffer often and early from cognitive impairment but are rarely appropriately prepared concerning end-of-life wishes. This reflects on their caregivers' burden as well. For symptomatic treatment of common symptoms such as fatigue, depression and cognitive impairment, methylphenidate has established an important role. For assessment of these symptoms, a shortened questionnaire Quality of Life Questionnaire-15-Palliative shows potential. Cancer-directed therapy in advanced stages of brain tumours has to be weighed critically. To assess adequate strategies to help patients and caregivers with the challenges of brain tumour-specific symptoms, randomized intervention studies are necessary. The same accounts for cancer-directed treatment in relation to quality of life in advanced stages of brain tumours.


Subject(s)
Brain Neoplasms/complications , Caregivers/psychology , Cognition Disorders/etiology , Depression/etiology , Palliative Care/standards , Quality of Life , Terminal Care/standards , Brain Neoplasms/psychology , Brain Neoplasms/therapy , Central Nervous System Diseases/etiology , Decision Making , Fatigue/etiology , Humans , Needs Assessment , Palliative Care/methods , Palliative Care/psychology , Prognosis , PubMed , Terminal Care/methods , Terminal Care/psychology
15.
Crit Care Med ; 39(7): 1766-72, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21494103

ABSTRACT

OBJECTIVE: To study the safety and the effects of early continuous hypertonic saline infusion in patients with cerebral edema and underlying cerebrovascular disease. DESIGN: Retrospective analysis. SETTING: University medical center. PATIENTS: Neurologic intensive care unit population with mixed cerebrovascular diseases. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between May 2008 and December 2009, 100 patients with severe intracerebral hemorrhage, cerebral ischemia, or aneurysmal subarachnoid hemorrhage and signs of intracranial hypertension received within ≤72 hrs after symptom onset a continuous infusion of hypertonic saline (3%, target sodium 145-155 mmol/L, target osmolality 310-320 mOsm/kg) over 13 (4-23) days. We analyzed the frequency of episodes with elevated intracranial pressure (new anisocoria or intracranial pressure >20 mm Hg for ≥20 mins), inhospital mortality, and the occurrence of adverse effects theoretically associated with hypertonic saline. The findings were compared with those of a historical control group (n = 115, 2007-2008) with equal underlying disease. In the treatment group, fewer episodes of critically elevated intracranial pressure (92 vs. 167, p = .027) in fewer patients (50 of 100 = 50.0% vs. 69 of 115 = 60.0% patients, p = .091) were observed, and inhospital mortality was significantly decreased (17.0% vs. 29.6%, p = .037). Adverse events, including cardiac arrhythmia, heart, liver or renal dysfunction, or pulmonary edema, occurred in both groups to a similar extent. CONCLUSIONS: Early and continuous infusion of hypertonic saline in patients with severe cerebrovascular disease and impending intracranial hypertension is safe and might reduce the frequency of intracranial pressure crises and mortality rate. A randomized controlled trial is warranted to confirm our findings and to evaluate the effects of hypertonic saline on functional outcomes.


Subject(s)
Brain Edema/drug therapy , Hospital Mortality , Intracranial Pressure/drug effects , Saline Solution, Hypertonic/therapeutic use , Aged , Brain Edema/etiology , Brain Edema/mortality , Brain Ischemia/complications , Cerebral Hemorrhage/complications , Female , Hemodynamics/drug effects , Humans , Male , Middle Aged , Osmolar Concentration , Retrospective Studies , Saline Solution, Hypertonic/adverse effects , Saline Solution, Hypertonic/pharmacology , Sodium/blood , Subarachnoid Hemorrhage/complications , Treatment Outcome , Water-Electrolyte Imbalance/etiology
16.
Stroke ; 40(5): 1907-9, 2009 May.
Article in English | MEDLINE | ID: mdl-19182084

ABSTRACT

BACKGROUND AND PURPOSE: Neuroprotective effects of induced hypothermia depend on its time point of initiation after acute brain injury. Preliminary studies in cardiac arrest patients indicate that rapid infusion of ice cold saline (ICS) is safe and effective for induction of hypothermia. We investigated its use in patients with acute ischemic stroke (AIS). METHODS: Patients (n=10) with AIS were included within 3 hours after symptom onset. After cranial CT, they were treated-if indicated-with rt-PA. ICS of 4 degrees C (25 mL/kg body weight) was administered via peripheral intravenous lines. Patients received buspirone/pethidine to prevent and treat shivering. After infusion of the target volume of ICS, no further efforts were made to maintain hypothermia by other methods. RESULTS: Ten patients with a median National Institutes of Health Stroke Scale (NIHSS) score of 5.5 (range 4 to 12) on admission were included into the study. Nine patients were treated with thrombolysis within a time window of 104+/-25 minutes. A mean amount of 2163+/-256 mL ICS was infused 17+/-11 minutes after rt-PA infusion had started. Tympanic temperature dropped significantly by a maximum of 1.6+/-0.3 degrees C (P<0.005) at 52+/-16 minutes after ICS was started. The procedure was well tolerated. The NIHSS score improved significantly to a median of 1 (range 1 to 15) at discharge compared to admission (P<0.02). CONCLUSIONS: This pilot study suggests that rapid ICS infusions in combination with pethidine and buspirone lower the body temperature significantly without major side effects.


Subject(s)
Brain Ischemia/therapy , Hypothermia, Induced/methods , Sodium Chloride , Stroke/therapy , Acute Disease , Aged , Analgesics, Opioid/therapeutic use , Blood Cell Count , Blood Chemical Analysis , Brain Ischemia/complications , Buspirone/therapeutic use , Cold Temperature , Data Interpretation, Statistical , Echocardiography , Electrocardiography , Female , Humans , Male , Meperidine/therapeutic use , Middle Aged , Pilot Projects , Serotonin Antagonists/therapeutic use , Shivering/drug effects , Shivering/physiology , Stroke/etiology , Thrombolytic Therapy , Tomography, X-Ray Computed
17.
Stroke ; 38(7): 2165-72, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17510456

ABSTRACT

BACKGROUND AND PURPOSE: The discovery of spontaneous neuronal replacement in the adult brain has shifted experimental stroke therapies toward a combined approach of preventing neuronal cell death and inducing neuronal plasticity. Brain-derived neurotrophic factor (BDNF) was shown to induce antiapoptotic mechanisms after stroke and to reduce infarct size and secondary neuronal cell death. Moreover, in intact animals, BDNF is a potent stimulator of adult neurogenesis. METHODS: The current study analyzed the effects of BDNF on induction of neuronal progenitor cell migration and sensorimotor recovery after cortical photothrombotic stroke. RESULTS: Daily intravenous bolus applications of BDNF during the first 5 days after stroke resulted in significantly improved sensorimotor scores up to 6 weeks. At the structural level, BDNF significantly increased neurogenesis in the dentate gyrus and enhanced migration of subventricular zone progenitor cells to the nearby striatum of the ischemic hemisphere. BDNF treatment could not, however, further stimulate progenitor cell recruitment to the cortex. CONCLUSIONS: These findings consolidate the role of BDNF as a modulator of neurogenesis in the brain and as an enhancer of long-term functional neurological outcome after cerebral ischemia.


Subject(s)
Brain Ischemia/drug therapy , Brain-Derived Neurotrophic Factor/pharmacology , Brain-Derived Neurotrophic Factor/therapeutic use , Neurons , Recovery of Function , Stroke/drug therapy , Animals , Behavior, Animal/physiology , Brain/anatomy & histology , Brain/drug effects , Brain/pathology , Brain/physiology , Brain Ischemia/pathology , Brain Ischemia/rehabilitation , Brain-Derived Neurotrophic Factor/administration & dosage , Cell Differentiation/drug effects , Cell Movement/drug effects , Male , Neurons/drug effects , Neurons/physiology , Random Allocation , Rats , Rats, Wistar , Stem Cells/drug effects , Stroke/pathology , Stroke Rehabilitation , Treatment Outcome
18.
J Clin Invest ; 115(8): 2083-98, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16007267

ABSTRACT

G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong anti-apoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neuronal differentiation in vitro. G-CSF markedly improved long-term behavioral outcome after cortical ischemia, while stimulating neural progenitor response in vivo, providing a link to functional recovery. Thus, G-CSF is an endogenous ligand in the CNS that has a dual activity beneficial both in counteracting acute neuronal degeneration and contributing to long-term plasticity after cerebral ischemia. We therefore propose G-CSF as a potential new drug for stroke and neurodegenerative diseases.


Subject(s)
Apoptosis/drug effects , Cell Differentiation/drug effects , Granulocyte Colony-Stimulating Factor/administration & dosage , Receptors, Granulocyte Colony-Stimulating Factor/biosynthesis , Stem Cells/metabolism , Stroke/drug therapy , Animals , Blood-Brain Barrier/metabolism , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Brain Ischemia/pathology , Disease Models, Animal , Granulocyte Colony-Stimulating Factor/biosynthesis , Granulocyte Precursor Cells/metabolism , Humans , Ligands , Male , Nerve Tissue/metabolism , Nerve Tissue/pathology , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neutrophils/metabolism , Rats , Rats, Wistar , Stroke/metabolism , Stroke/pathology
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