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Biomedical subjects

Daniel Becker

Publications and source records attributed to Daniel Becker.

At least 19 recordsLinked to original sources
PubMed2006

Improving SVT discrimination in single-chamber ICDs: a new electrogram morphology-based algorithm.

INTRODUCTION: Wide-spread adoption of ICD therapy has focused efforts on improving the quality of life for patients by reducing "inappropriate" shock therapies. To this end, distinguishing supraventricular tachycardia from ventricular tachycardia remains a major challenge for ICDs. More sophisticated discrimination algorithms based on ventricular electrogram morphology have been made practicable by the increased computational ability of modern ICDs. METHODS AND RESULTS: We report results from a large prospective study (1,122 pts) of a new ventricular electrogram morphology tachycardia discrimination algorithm (Wavelet Dynamic Discrimination, Medtronic, Minneapolis, MN, USA) operating at minimal algorithm setting (RV coil-can electrogram, match threshold of 70%). This is a nonrandomized cohort study of ICD patients using the morphology discrimination of the Wavelet algorithm to distinguish SVT and VT/VF. The Wavelet criterion was required ON in all patients and all other supraventricular tachycardia discriminators were required to be OFF. Spontaneous episodes (N = 2,235) eligible for ICD therapy were adjudicated for detection algorithm performance. The generalized estimating equations method was used to remove bias introduced when an individual patient contributes multiple episodes. Inappropriate therapies for supraventricular tachycardia were reduced by 78% (90% CI: 72.8-82.9%) for episodes within the range of rates where Wavelet was programmed to discriminate. Sensitivity for sustained ventricular tachycardia was 98.6% (90% CI: 97-99.3%) without the use of high-rate time out. CONCLUSIONS: Results from this prospective study of the Wavelet electrogram morphology discrimination algorithm operating as the sole discriminator in the ON mode demonstrate that inappropriate therapy for supraventricular tachycardia in a single-chamber ICD can be dramatically reduced compared to rate detection alone.

Algorithms↗
PubMed2006

Robust Salmonella metabolism limits possibilities for new antimicrobials.

New antibiotics are urgently needed to control infectious diseases. Metabolic enzymes could represent attractive targets for such antibiotics, but in vivo target validation is largely lacking. Here we have obtained in vivo information about over 700 Salmonella enterica enzymes from network analysis of mutant phenotypes, genome comparisons and Salmonella proteomes from infected mice. Over 400 of these enzymes are non-essential for Salmonella virulence, reflecting extensive metabolic redundancies and access to surprisingly diverse host nutrients. The essential enzymes identified were almost exclusively associated with a small subgroup of pathways, enabling us to perform a nearly exhaustive screen. Sixty-four enzymes identified as essential in Salmonella are conserved in other important human pathogens, but almost all belong to metabolic pathways that are inhibited by current antibiotics or that have previously been considered for antimicrobial development. Our comprehensive in vivo analysis thus suggests a shortage of new metabolic targets for broad-spectrum antibiotics, and draws attention to some previously known but unexploited targets.

Animals↗
PubMed2006

Patient Alert to detect ICD lead failure: efficacy, limitations, and implications for future algorithms.

AIMS: An algorithm that alerts implantable cardioverter-defibrillator (ICD) patients, in case of abnormal lead impedance (Patient Alerttrade mark, Medtronic), may help to recognize lead dysfunction. We aimed to determine the utility of Patient Alert for ICD lead-failure detection in a prospective study. METHODS AND RESULTS: Three hundred and sixty ICD patients were followed for 22+/-14 months. Patient Alert was active for pacing impedance <200 and >2000-3000 Omega, and high-voltage conductor impedance <10-20 and >200 Omega. Ten alert events and a total of 29 severe system complications occurred. Patient Alert detected three of 10 ICD lead failures, with a positive predictive value (PPV) of 77.8% for any severe system complication. Retrospective analysis identified 23 patients with a sensing integrity counter (SIC) >300 and revealed an additional four prior undetected lead defects. SIC detected ICD lead failure with 92.9% sensitivity and a PPV of 59.1%. Eight of nine patients with a false-positive SIC had an integrated bipolar lead. Patient Alert combined with SIC detected all ICD lead failures and 71.4% of all severe lead complications. CONCLUSIONS: Patient Alert, based on daily lead-impedance measurement, detected one-third of all ICD lead failures. Combined use with continuous lead integrity monitoring (SIC) increased sensitivity to 100%. Integrated bipolar leads may yield a false-positive SIC. Incorporating SIC and automated pace/sense threshold measurement may improve Patient Alert sensitivity for severe lead complications.

Aged↗
PubMed2006

Wavelet-based tachycardia discrimination in ICDs: Impact of posture and electrogram configuration.

BACKGROUND: Inappropriate therapy delivery is an important concern in the management of patients with implantable cardioverter defibrillators (ICDs). Recently, a morphology-based algorithm (wavelet feature) has been introduced for differentiation of ventricular and supraventricular tachycardia. In this study, we evaluated the performance of the wavelet algorithm using various electrogram (EGM) configurations during different body positions. METHODS: Patients with a single-chamber Medtronic model 7230 ICD (Minneapolis, MN, USA) and a double-coil lead were included. EGM templates were collected during baseline rhythm in supine position for different EGM sources (right ventricular [RV] coil-can, RV coil-superior vena cava [SVC] coil, tip-ring, SVC coil-can). For each EGM configuration, morphologic similarity (match percentage) of EGMs obtained during different body positions (supine, left and right lateral, sitting, standing, walking) were compared with the templates. RESULTS: Twenty-eight patients (24 males; age 58 +/- 17 years) were studied. A total of 9,775 intracardiac EGMs were analyzed. Median match percentage (interquartile range) was 88% (85-94), 88% (82-94), 82% (76-88), and 73 (58-85) for the RV coil-can, RV coil-SVC coil, tip-ring, and SVC coil-can configurations, respectively. Correct classification rates, as defined by match percentage of 70% or higher, were significantly higher with the RV coil-can, RV coil-SVC coil, and tip-ring EGM configurations, as compared to the SVC coil-can configuration (95, 91, and 91 vs 58% > or =70% match percent, P < 0.001). CONCLUSION: Wavelet-based morphology scores in ICDs may change with various body positions. These variations are relatively minor using the nominal configuration (RV coil-can), as well as by using RV coil-SVC coil and tip-ring. However, morphology scores can vary considerably when SVC coil-can is used; therefore, this configuration should be avoided while using the wavelet algorithm.

Algorithms↗
PubMed2006

Therapy for the middle-aged: the relevance of existential issues.

Middle age is a normative developmental stage. Although further research is still required, there is general agreement in the literature as to the principal changes, conflicts, and tasks that are characteristic of this stage in life, and in particular, as to the nature of the transition to the second half of life, or what is commonly known as "midlife crisis." The dynamic psychotherapeutic approach to the middle-aged patient does not differ in essence from that adopted toward adolescents or the elderly. The current paper suggests that introducing existential issues and the existentialist therapy approach into analytic-oriented therapy is especially appropriate to the psychotherapy of individuals in midlife. The central themes of middle-age psychology are presented, and the relevance of the existentialist therapy approach is discussed in this context, with reference to four fundamental elements of the "existential discourse": death, isolation, freedom, and meaning.

Adult↗
PubMed2005

Generating chimeric spinal cord: a novel model for transplantable oligodendrocyte progenitors derived from embryonic stem cells.

OBJECT: To identify and evaluate stem cell-derived oligodendrocytes obtained for cell transplantation therapies, the authors developed a novel model to examine single, adult oligodendrocytes in situ. METHODS: Green fluorescent protein-expressing, mouse embryonic stem cells (ESCs) were neural induced and additionally staged in an oligosphere preparatory step for high-yield derivation of oligodendrocyte progenitors. These transplantable, induced progenitors were injected into postnatal Day 2 rat pups, in which spinal cord sections were then examined at 3 and 9 weeks posttransplantation. CONCLUSIONS: Transplanted oligosphere ESCs survived and integrated anatomically into postnatal and adult white matter, generating targeted regions of chimeric spinal cord. A simple model for identifying adult oligodendrocytes in situ is presented, which is suitable for use in further studies examining functional myelination and derivation of oligodendrocytes from genetically engineered ESC lines, including human ESCs. Results from the model presented here demonstrate a unique method for examining transplantable oligodendrocyte progenitors derived from ESCs for repair of white matter disease.

Animals↗
PubMed2005

TRPV4 exhibits a functional role in cell-volume regulation.

Tight regulation of the cell volume is important for the maintenance of cellular homeostasis. In a hypotonic environment, cells swell owing to osmosis. With many vertebrate cells, swelling is followed by an active reduction of volume, a process called regulatory volume decrease (RVD). A possible participant in RVD is the non-selective cation channel TRPV4, a member of the TRP superfamily that has been shown to react to hypotonic stimuli with a conductance for Ca2+. As a model for cell-volume regulation, we used a human keratinocyte cell line (HaCaT) that produces TRPV4 endogenously. When HaCaT cells were exposed to a hypotonic solution (200 mOsm) maximal swelling was followed by RVD. During swelling and volume regulation, a strong Ca2+ influx was measured. Gd3+, an inhibitor of TRPV4, blocked RVD of HaCaT cells and the accompanying rise of cytosolic Ca2+. To define the role of TRPV4 in volume regulation, a TRPV4-EGFP fusion protein was produced in CHO cells. CHO cells are unable to undergo RVD under hypotonic conditions and do not produce TRPV4 endogenously. Fluorescence imaging revealed that recombinant TRPV4 was localized to the cell membrane. Production of TRPV4 enabled CHO cells to undergo typical RVD after hypo-osmolarity-induced cell swelling. RVD of TRPV4-transfected CHO cells was significantly reduced by Gd3+ treatment or in Ca2+-free solution. Taken together, these results show a direct participation of TRPV4 in RVD.

Animals↗
PubMed2005

Network of communities in the fight against AIDS: local actions to address health inequities and promote health in Rio de Janeiro, Brazil.

When combined with major social inequities, the AIDS epidemic in Brazil becomes much more complex and requires effective and participatory community-based interventions. This article describes the experience of a civil society organisation, the Centre for Health Promotion (CEDAPS), in the slum communities (favelas) of Rio de Janeiro, Brazil. Using a community-based participatory approach, 55 community organisations were mobilised to develop local actions to address the increasing social vulnerability to HIV/AIDS of people living in squatter communities. This was done through on-going prevention initiatives based on the local culture and developed by a Network of Communities. The community movement has created a sense of "ownership" of social actions. The fight against AIDS has been a mobilising factor in engaging and organising communities and has contributed to raising awareness of health rights. Local actions included targeting the determinants of local vulnerability, as suggested by health promotion workers.

Acquired Immunodeficiency Syndrome↗
PubMed2005

An innovative geographical approach: health promotion and empowerment in a context of extreme urban poverty.

This article describes and analyses a territorial intervention, the Vila Paciencia Initiative--a local development/health promotion programme implemented in a context of extreme poverty in the western district of Rio de Janeiro. The main goal of the programme was to empower individuals and communities. We emphasise the lessons learned and the potential for integrating them into local and regional health services, which could strengthen community participation and capacity-building and improve the effectiveness and community orientation of primary health care and other public policies directed to geographical development.

Brazil↗
PubMed2005

Multi-germ layer lineage central nervous system repair: nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain.

OBJECT: To restore proper function to a damaged central nervous system (CNS) through transplantation, it is necessary to replace both neural and nonneural elements that arise from different germ layers in the embryo. Mounting evidence indicates the importance of signals related to vasculogenesis in governing neural proliferation and differentiation in early CNS development. Here, the authors examined whether embryonic stem cell (ESC)-derived progenitors can selectively generate both neural and endothelial cells after transplantation in the damaged CNS. METHODS: Injections of 20 nmol N-methyl-D-aspartate created a unilateral striatal injury in 7-day-old rats. One week postinjury, murine ESCs, neural-induced with retinoic acid, were transplanted into the injured striatum. Histological staining, laser confocal microscopy, and transmission electron microscopy of grafted ESCs were performed 1 week posttransplantation. CONCLUSIONS: Transplanted ESCs differentiated into neural cells, which segregated into multiple pools and formed neurons that conformed to host cytoarchitecture. The ESCs also generated endothelial cells, which integrated with host cells to form chimeric vasculature. The combination of ESC pluripotentiality and multiple germ layer differentiation provides a new conceptual framework for CNS repair.

Animals↗
PubMed2004

Repair of the injured spinal cord and the potential of embryonic stem cell transplantation.

Traditionally, treatment of spinal cord injury seemed frustrating and hopeless because of the remarkable morbidity and mortality, and restricted therapeutic options. Recent advances in neural injury and repair, and the progress towards development of neuroprotective and regenerative interventions are basis for increased optimism. Neural stem cells have opened a new arena of discovery for the field of regenerative science and medicine. Embryonic stem (ES) cells can give rise to all neural progenitors and they represent an important scientific tool for approaching neural repair. The growing number of dedicated regeneration centers worldwide exemplifies the changing perception towards the do-ability of spinal cord repair and this review was born from a presentation at one such leading center, the Kentucky Spinal Cord Injury Research Center. Current concepts of the pathophysiology, repair, and restoration of function in the damaged spinal cord are presented with an overlay of how neural stem cells, particularly ES cells, fit into the picture as important scientific tools and therapeutic targets. We focus on the use of genetically tagged and selectable ES cell lines for neural induction and transplantation. Unique features of ES cells, including indefinite replication, pluripotency, and genetic flexibility, provide strong tools to address questions of neural repair. Selective marker expression in transplanted ES cell derived neural cells is providing new insights into transplantation and repair not possible previously. These features of ES cells will produce a predictable and explosive growth in scientific tools that will translate into discoveries and rapid progress in neural repair.

Animals↗
PubMed2003

Restoring function after spinal cord injury.

BACKGROUND: By affecting young people during the most productive period of their lives, spinal cord injury is a devastating problem for modern society. A decade ago, treating SCI seemed frustrating and hopeless because of the tremendous morbidity and mortality, life-shattering impact, and limited therapeutic options associated with the condition. Today, however, an understanding of the underlying pathophysiological mechanisms, the development of neuroprotective interventions, and progress toward regenerative interventions are increasing hope for functional restoration. REVIEW SUMMARY: This study addresses the present understanding of SCI, including the etiology, pathophysiology, treatment, and scientific advances. The discussion of treatment options includes a critical review of high-dose methylprednisolone and GM-1 ganglioside therapy. The concept that limited rebuilding can provide a disproportionate improvement in quality of life is emphasized throughout. CONCLUSIONS: New surgical procedures, pharmacologic treatments, and functional neuromuscular stimulation methods have evolved over the last decades that can improve functional outcomes after spinal cord injury, but limiting secondary injury remains the primary goal. Tissue replacement strategies, including the use of embryonic stem cells, become an important tool and can restore function in animal models. Controlled clinical trials are now required to confirm these observations. The ultimate goal is to harness the body's own potential to replace lost central nervous system cells by activation of endogenous progenitor cell repair mechanisms.

Humans↗
PubMed2003

Spinal cord injury: promising interventions and realistic goals.

Long regarded as impossible, spinal cord repair is approaching the realm of reality as efforts to bridge the gap between bench and bedside point to novel approaches to treatment. It is important to recognize that the research playing field is rapidly changing and that new mechanisms of resource development are required to effectively make the transition from basic science discoveries to effective clinical treatments. This article reviews recent laboratory studies and phase 1 clinical trials in neural and nonneural cell transplantation, stressing that the transition from basic science to clinical applications requires a parallel rather than serial approach, with continuous, two-way feedback to most efficiently translate basic science findings, through evaluation and optimization, to clinical treatments. An example of mobilizing endogenous stem cells for repair is reviewed, with emphasis on the rapid application of basic science to clinical therapy. Successful and efficient transition from basic science to clinical applications requires (1) a parallel rather than a serial approach; (2) development of centers that integrate three spheres of science, translational, transitional, and clinical trials; and (3) development of novel resources to fund the most critically limited step of transitional to clinical trials.

Animals↗
PubMed2003

Risperidone, but not olanzapine, decreases bone mineral density in female premenopausal schizophrenia patients.

BACKGROUND: The hyperprolactinemia induced by conventional antipsychotics often leads to osteoporosis. The commonly used atypical antipsychotics risperidone and olanzapine vary in their hyperprolactinemic properties. Therefore, we compared hormone profiles and bone properties in female premenopausal schizophrenia patients treated with either risperidone or olanzapine. METHOD: In a cross-sectional study, consecutive premenopausal, female, DSM-IV schizophrenia patients who were treated with either risperidone (N = 12) or olanzapine (N = 14) for at least 2 years were included. Dual energy X-ray absorptiometry evaluated bone mineral density, and multisite quantitative ultrasound measured bone speed of sound. In addition, profiles of urinary excretion of deoxypyridinoline and circulating levels of hormones and lipids were assessed. RESULTS: Serum prolactin levels were higher in the risperidone-treated group as compared with the olanzapine subjects (123 +/- 144 and 25.9 +/- 25.7, p <.05). Whereas bone mineral density was similar in the treatment groups, bone speed of sound was lower in the risperidone group as compared with the olanzapine-treated group. Expressed as age-adjusted Z score, bone speed of sound at the radius was -0.31 and 0.58, respectively, p <.05, and at the phalanx, -1.41 and 0.04, respectively, p <.05. The bone speed of sound in the risperidone-treated patients inversely correlated with urinary deoxypyridinoline excretion (r = 0.73, p <.05). CONCLUSION: Risperidone treatment, as opposed to olanzapine, for female premenopausal schizophrenia results in hyperprolactinemia and clinically relevant decrease in bone mineral density. The calculated relative risk for fragility fracture of women treated with risperidone as compared to those treated with olanzapine is 1.78 when bone speed of sound was measured at the phalanx and 1.23 when measured at the radius.

Absorptiometry, Photon↗
PubMed2002

Clock drawing test in mild and moderate dementia of the Alzheimer's type: a comparative and correlation study.

OBJECTIVES: (a) To compare two different clock drawing tests (CDTs) in mild and moderate dementia of the Alzheimer's type (DAT); (b) To examine presumed correlation between these CDTs and some demographic, cognitive and activities of daily living (ADL) variables in mild and moderate DAT. METHODS: Cross-sectional study. Psychogeriatric outpatient clinic. 49 DAT patients, total; 26-mild, 23-moderate, mean age 77.8 and 80.6, respectively. Evaluations included the Mini-Mental State Examination (MMSE), the Cambridge Cognitive Examination (CAMCOG), the Instrumental Activities of Daily Living Scale (IADL), and a Basic Activities of Daily Living (BADL)-dressing subscale. Severity of dementia was determined with the Clinical Dementia Rating (CDR). Each clock was blindly scored by the same investigator, according to Shulman's and Freedman's methods. RESULTS: Mild and moderate DAT groups were similar in age, gender and education. Performance on Shulman's clock was similar between groups while moderate DAT subjects performed significantly worse on Freedman's clock compared to mild DAT patients. Both clocks correlated highly in mild and moderate DAT. CDT scores correlated significantly with age and education only in mild DAT. Neither clock correlated with ADLs in either stage of dementia severity. CDTs correlated with the MMSE score, and the CAMCOG score in mild DAT, and only with the CAMCOG score in moderate DAT. These correlations were still significant after controlling for age and education. CONCLUSIONS: Different aspects of cognition and dementia severity are reflected depending on how a clock drawing is scored. Some scoring systems may have greater sensitivity than others in monitoring progression of cognitive deterioration. Correlation between different CDTs and the variables studied (demographic, cognitive, ADLs), when present, is not ubiqitous and changes with the dementia severity.

Activities of Daily Living↗