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Analysis of parameters for epidural spinal cord stimulation. 3. Topographical distribution of paresthesiae--a preliminary analysis of 266 combinations with contacts implanted in the midcervical and midthoracic vertebral levels.

As a part of the systematic analysis of parameters involved in electrical epidural spinal cord stimulation therapy, distribution of paresthesiae in accordance with the position of contacts, as related to midline and vertebral level of contacts, was investigated. A preliminary analysis performed for 266 combinations having contacts implanted in the midcervical and low-thoracic vertebral levels showed that the topographical spread of the paresthesiae did not always cover the classical dermatomes. Significant paresthesiae spread was found as follows: C4-midline, unipolar combinations; the hand, forearm and upperarm, bipolar combinations; the hand, forearm; C4-lateral, unipolar combinations: the anterior shoulder, forearm, upper arm and hand, bipolar combinations: the hand, forearm and upper arm; T10-midline, unipolar combinations: the anterior and posterior of thigh, leg, knee, ankle and foot, bipolar combinations: the anterior and posterior thigh, leg, knee and foot; T10-lateral, unipolar combinations: the abdomen, anterior leg, knee and anterior thigh, bipolar combinations: the anterior thigh, anterior leg, knee and foot. This preliminary analysis suggests that more detailed studies would be worthwhile in the investigation of sensory responses to electrical stimulation of the spinal cord with epidural electrodes. Findings from such investigations could also be useful to extend our present anatomical knowledge of central and peripheral sensory neural structures.

Cervical Vertebrae↗

Interventions to reduce the burden of caregiving for an adult with dementia: a meta-analysis.

Because of conflicting results, in order to clarify the state of the science it was necessary to do a systematic analysis of the literature on research testing the effect of interventions on the burden of persons caring for family members with dementia. The purpose of this study was to evaluate, using meta-analytic techniques, those intervention strategies (support group, education, psychoeducation, counseling, respite care, and multicomponent) designed to help caregivers cope with the burden of caregiving. Using meta-analytic methods developed by Glass, McGraw, and Smith (1981) and Hedges and Olkin (1985), 24 published research reports testing 27 treatments for caregivers of adults with dementia were synthesized. Overall, the analysis showed that collectively the interventions had no effect on caregiver burden. Only the category of multicomponent interventions significantly reduced caregiver burden. Burden may be too global an outcome to be affected consistently by intervention. Better and more precise measures are needed to evaluate the effects of caregiver interventions properly.

Caregivers↗

Analysis of the cardiac rhythm preceding episodes of paroxysmal atrial fibrillation.

AIMS: This study seeks to elucidate whether there was a common mode of initiation of paroxysmal atrial fibrillation (PAF) episodes that might suggest new therapies. METHODS: A library of 177 digitized and analyzed 24-hour Holter recordings from PAF pharmacotherapy trials was studied. All noise-free PAF episodes > or =0.5 minutes were identified. PAF episodes and the preceding 2 minutes of sinus rhythm were printed as tachograms and visually inspected. Heart rate and ectopic beat behavior were used to characterize modes of PAF onset by comparing half-minute segments of the final 2 minutes of sinus rhythm. RESULTS: Thirty-four recordings (from 19 patients, aged 61.7 +/- 11.5 years) provided 231 PAF episodes suitable for analysis. No patients had a consistent mode of PAF onset. This was confirmed by systematic analysis of the five patients with the most episodes. Overall, a highly significant increase in ectopic beats, from 1.34 to 6.52 min(-1) (p < 0.001) was found, but heart rate did not significantly change (mean heart rate at onset = 64 beats/min). PAF was initiated by a solitary ectopic beat in more than half of the cases. No consistent evidence for short-long-short sequences, seen in ventricular arrhythmias, was found. CONCLUSION: The mode of onset of atrial fibrillation is inconsistent, both across a population with PAF and within individuals. This has implications for understanding the mechanisms of atrial fibrillation onset in human beings and for the treatment of the disorder.

Atrial Fibrillation↗

[Analysis of the medico-economic literature comparing primary angioplasty and thrombolysis in the management of acute myocardial infarction].

OBJECTIVE: To assess the generalizability of the medico-economic analysis comparing primary coronary angioplasty and thrombolytic therapy for acute myocardial infarction. METHOD: A systematic analysis of published studies was performed by two independent reviewers, in accordance with guidelines promulgated by health economic experts. RESULTS: Eleven articles, which concerned seven studies, were selected. Respectively, four evaluations were carried out in U.S. and three other in European countries (France, Netherland and Austria). There were three randomized trials, two observational studies and two decision trees. The costs were respectively ranged 2042 to 83,708 1999 US dollars for thrombolytic therapy and 3289 to 83,477 1999 US dollars for angioplasty. In two randomized trials and one decisional tree, the primary coronary angioplasty was both more effective and less costly than the thrombolysis therapy. One observational study concluded that thrombolytic therapy was less costly than primary angioplasty despite comparable effectiveness. Two analysis could not conclude of a difference between the alternatives, because of lack of statistical power. DISCUSSION: Published medico-economic analysis remain of a little interest for the French health care system because of lack of transparency in presentation of results. The dominance of the primary angioplasty was sensitive to time required for patient's transfer (ideally less than an hour), to the presence of redundant laboratories in an area and to the presence of an experienced staff for 24 h a day.

Angioplasty↗

Blood volume, aerobic power, and endurance performance: potential ergogenic effect of volume loading.

OBJECTIVE: Blood volume (BV) and hemoglobin concentration ([Hb]) play important roles in oxygen transport. Manipulation of both BV and [Hb] can markedly affect systemic oxygen transport and maximal aerobic capacity (VO2max). However, the role of BV in oxygen transport and aerobic performance is not well understood. It has recently been postulated that an acute expansion of BV using plasma volume (PV), independent of changes in [Hb], may represent a potential ergogenic property. Therefore, the primary objective of this review was to determine the potential ergogenic properties of volume loading. DATA SOURCES: An extensive research of Medline and Sport-Discus along with cross-referencing was conducted. Articles were included on the basis of their relevancy to the purpose of this review. Only articles published in English were included in the analysis. STUDY SELECTION: All study designs using human participants were reviewed. DATA EXTRACTION: A systematic analysis of data regarding the effect of BV on the determination of oxygen transport, aerobic capacity, and endurance performance was conducted. Particular emphasis was given to articles that examined BV as the key independent variable. Articles relevant to the evaluation of the impact of BV on aerobic capacity and endurance performance were reviewed according to the strengths of the individual study designs. RESULTS: Seven investigations evaluated the impact of acute changes in BV, independent of changes in [Hb], on VO2max. Of these investigations, three revealed that acute manipulations of BV result in no change or a slight reduction in VO2max. Three investigations revealed a significant improvement in VO2max after acute PV expansion. One investigation revealed a nonsignificant increase in VO2max after acute PV expansion. Seven investigations evaluated the impact of acute changes in BV, independent of changes in [Hb], on endurance performance: two revealed a significant improvement in endurance performance after acute PV expansion, and five revealed an unchanged or reduced endurance performance after acute PV expansion. The majority of investigations showing an improvement in VO2max and/or endurance performance after acute PV expansion were conducted using untrained individuals. CONCLUSION: Volume loading does not result in an improvement in VO2max and/or endurance performance in endurance athletes. Volume loading in untrained individuals may improve VO2max, but does not bring these individuals to the aerobic capacity of endurance-trained athletes. Also, volume loading generally does not lead to improvement in endurance performance, irrespective of its effects on VO2max.

Adult↗

Spinal cord stimulation for chronic back and leg pain and failed back surgery syndrome: a systematic review and analysis of prognostic factors.

STUDY DESIGN: Systematic review. OBJECTIVES: To assess efficacy and safety of spinal cord stimulation in patients with chronic leg and back pain and failed back surgery syndrome and to examine prognostic factors that predict spinal cord stimulation outcome. SUMMARY OF BACKGROUND DATA: A previous systematic review of spinal cord stimulation in patients with chronic back and leg pain and failed back surgery syndrome by Turner et al in 1995 identified 39 case studies and no controlled studies. METHODS: A number of electronic databases were searched through January 2002. Citation searching of included papers was undertaken, and gray literature was sought through contact with clinical experts. No language restrictions were applied. All controlled and noncontrolled study designs were included. Study selection was carried out independently by two reviewers. Prognostic factors (age, sex, duration of pain, time post surgery, follow-up duration, publication year, data collection year, indication, data collection country, study setting, and quality score) responsible for pain relief outcome across case series were examined using univariate and multivariate metaregression. RESULTS: One randomized controlled trial, one cohort study, and 72 case studies were included. The randomized controlled trial reported a significant benefit (P = 0.047) in the proportion of patients with failed back surgery syndrome reporting 50% or more pain relief with spinal cord stimulation (37.5%) compared with patients undergoing back reoperation (11.5%). There was evidence of substantial statistical heterogeneity (P < 0.0001) in the level of pain relief following spinal cord stimulation reported across case series studies. The four principal prognostic factors found to be predictive of increased level of pain relief with spinal cord stimulation were poor study quality score, short follow-up duration, multicenter (versus single center) studies, and the inclusion of patients with failed back surgery syndrome (versus chronic back and leg pain). Overall, 43% of patients with chronic back and leg pain/failed back surgery syndrome experienced one or more complications following a spinal cord stimulation implant, although no major adverse events were reported. CONCLUSIONS: Despite an increase in the number of studies over the last 10 years, the level of evidence for the efficacy of spinal cord stimulation in chronic back and leg pain/failed back surgery syndrome remains "moderate." Prognostic factors found to be predictive of the level of pain relief following spinal cord stimulation were study quality, follow-up duration, study setting, and patient indication.

Back Pain↗

Gene expression profiling of breast cancer.

Numerous genes are controlled by complex regulatory networks and involved in the development and progression of breast cancer, and these genes are the key factors determining each characteristic of the tumor. Gene expression profiling, a large scale analysis of gene expression, has created new possibilities for the molecular characterization of cancer. Systematic analysis of expression patterns of thousands of genes in tumor cells using DNA microarrays and correlation of these patterns to specific features of phenotypic variation may provide the basis for an improved taxonomy of cancer. These profiles have the potential to explain the genetic heterogeneity of breast cancer and allow treatment strategies to be planned in accordance with their probability of success in individual patients.

Antineoplastic Agents↗

Analyzing process variation in chart review using a networked spreadsheet application in the Walter Reed Army Medical Center Nephrology Clinic.

The role of reviewer variation in interpreting outcomes of outpatient clinic chart reviews has been poorly studied. The present study used results collected from a network-based spreadsheet application (Microsoft Excel), which is widely available throughout the Army Medical Department, for chart reviews. Data were collected from January 1998 to August 2000, and 2,308 charts of 1,127 patients were reviewed. Results showed a significant improvement in documentation of contact with the referring provider from 1998 to 2000 (55.9% in 1998, 81.6% in 1999, and 80.6% in 2000; p < 0.01 by chi 2 for both). The percentage of charts for new consultations with inadequately controlled blood pressure managed appropriately improved from 73.7% in 1999 to 89.2% in 2000 (p < 0.01 by chi 2). These results persisted in logistic regression analysis controlling for different reviewers. In conclusion, widely available office automation tools allow the systematic analysis of chart review data with the potential to improve practice patterns.

Chi-Square Distribution↗

Meta-analysis: a tool for medical and scientific discoveries.

Medicine has made increasing use of meta-analysis, largely as a quantitative procedure for combining results of clinical trials. Meta-analysis begins with a comprehensive review of the literature. The next step is a systematic analysis of the quality and content of each study. Finally, results are combined statistically and conclusions are drawn from this new overview of the data. This paper presents a brief historical perspective on the use of meta-analysis in medicine with emphasis on the medical library. The authors conclude that in the future, medical librarians will play a significant role in the application of this useful technique.

History, 20th Century↗

[The analysis of nervous system functions in dysmorphic syndromes].

The involvement of the C.N.S. in dysmorphic syndromes is very frequent; therefore a systematic analysis of the functions of the nervous system is important in the clinical definition of these syndromes. Besides the morphological aspects, studied by magnetic resonance imaging, investigations should be carried out in the neuroelectrophysiological and neuropsychological fields. For the former, the following examinations are proposed: EEG in wakefulness and sleep, multimodal evoked potentials (VEP, BAEP, SEP), cortical magnetic stimulation and P300 (P3). For the neuropsychological field, a general intelligence test appropriate to the mental age of the subject (the Wechsler, Terman-Merrill, or Brunet-Lezine scale) and, whenever possible, the following complementary tests: Raven's Progressive Matrices, Bender's and Santucci's graphic tests, go-no go, Goodenough draw-a-person, reading and writing tests, Langeot's scale for development of the logical thinking, sorting test and verbal and spatial memory tests. In some cases, the behaviour should be defined, through Conner's scale for attention deficit-hyperactivity disorders, the Autism Diagnostic Interview, the Adaptive Behaviour Scale and the Brief Psychiatric Rating Scale.

Congenital Abnormalities↗

Comparative gene expression in the symbiotic and aposymbiotic Aiptasia pulchella by expressed sequence tag analysis.

Intracellular symbiotic relationships are prevalent between cnidarians, such as corals and sea anemones, and the photosynthetic dinoflagellate symbionts. However, there is little understanding about how the genes express when the symbiotic relationship is set up. To characterize genes involved in this association, the endosymbiosis between sea anemone, Aiptasia pulchella, and dinoflagellate zooxanthellae, Symbiodinium spp., was employed as a model. Two complementary DNA (cDNA) libraries were constructed from RNA isolated from symbiotic and aposymbiotic A. pulchella. Using single-pass sequencing of cDNA clones, a total of 870 expressed sequence tags (ESTs) clones were generated from the two libraries: 474 from symbiotic animal and 396 from aposymbiotic animal. The initial ESTs consisted of 143 clusters and 231 singletons. A BLASTX search revealed that 147 unique genes had similarities with protein sequences available from databases; 120 of these clones were categorized according to their putative function. However, many ESTs could not assign functionally. The putative roles of some of the identified genes relative to endosymbiosis were discussed. This is the first report of the use of EST analysis to examine the gene expression in symbiotic and aposymbiotic states of the cnidarians. The systematic analysis of EST from this study provides a useful database for future investigations of the molecular mechanisms involved in algal-cnidarian symbiosis.

Animals↗

Development of Molecular Approaches to Early Lung Cancer Detection.

Lung cancer has been particularly recalcitrant to standard therapeutic interventions. Improvement in the outcome for this disease requires the ability to identify the disease while it is still localized in the airways. Usually, radiation therapy to eliminate this disease fails because of progression of the cancer outside the radiation treatment ports. This is a failure of the diagnostic modalities to detect the extent of the cancer, not a failure of the radiation. With new epithelial-directed diagnostics, the ability to detect the premetastatic phase of lung cancer is emerging. Evolution of the screening infrastructure will be required to allow percolation of this technology out to the medical community, so that a benefit in cancer mortality reduction can be achieved. Some development issues will have to be resolved. Considering our fragmentary understanding of pulmonary carcinogenesis, the heterogeneity of lung cancer suggests that a panel of biomarkers instead of a single marker will be required to clarify the status of an individual's epithelium. However, the data output from multiplexed bioassays performed on large clinical populations will require better integration of information technology to optimize analysis and reporting of test results. An important new area for outcomes research is the systematic analysis of population screening approaches. With population sampling algorithms, selective screening. This type of research requires careful clinical validation. Finally, the general acceptance of population-based screening will be determined by the availability of effective interventions to complement the new diagnostic tools. New measures to prevent the progression of early cancer will be discussed.

Journal Article↗

Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of immunodominant regions of human immunodeficiency virus type 1 subtype C.

A systematic analysis of immune responses on a population level is critical for a human immunodeficiency virus type 1 (HIV-1) vaccine design. Our studies in Botswana on (i) molecular analysis of the HIV-1 subtype C (HIV-1C) epidemic, (ii) frequencies of major histocompatibility complex class I HLA types, and (iii) cytotoxic T-lymphocyte (CTL) responses in the course of natural infection allowed us to address HIV-1C-specific immune responses on a population level. We analyzed the magnitude and frequency of the gamma interferon ELISPOT-based CTL responses and translated them into normalized cumulative CTL responses. The introduction of population-based cumulative CTL responses reflected both (i) essentials of the predominant virus circulating locally in Botswana and (ii) specificities of the genetic background of the Botswana population, and it allowed the identification of immunodominant regions across the entire HIV-1C. The most robust and vigorous immune responses were found within the HIV-1C proteins Gag p24, Vpr, Tat, and Nef. In addition, moderately strong responses were scattered across Gag p24, Pol reverse transcriptase and integrase, Vif, Tat, Env gp120 and gp41, and Nef. Assuming that at least some of the immune responses are protective, these identified immunodominant regions could be utilized in designing an HIV vaccine candidate for the population of southern Africa. Targeting multiple immunodominant regions should improve the overall vaccine immunogenicity in the local population and minimize viral escape from immune recognition. Furthermore, the analysis of HIV-1C-specific immune responses on a population level represents a comprehensive systematic approach in HIV vaccine design and should be considered for other HIV-1 subtypes and/or different geographic areas.

Amino Acid Sequence↗

Analysis of a distributed model of leg coordination. I. Individual coordination mechanisms.

Using tools from discrete dynamical systems theory, we begin a systematic analysis of a distributed model of leg coordination with both biological and robotic applications. In this paper, we clarify the role of individual coordination mechanisms by studying a system of two leg oscillators coupled in one direction by each of the three major mechanisms that have been described for the stick insect Carausius morosus. For each mechanism, we derive analytical return maps, and analyze the behavior of these return maps under iteration in order to determine the asymptotic phase relationship between the two legs. We also derive asymptotic relative phase densities for each mechanism and compare these densities to those obtained from numerical simulations of the model. Our analysis demonstrates that, although each of these mechanisms can individually compress a range of initial conditions into a narrow band of relative phase, this asymptotic relative phase relationship is, in general, only neutrally stable. We also show that the nonlinear dependence of relative phase on walking speed along the body in the full hexapod model can be explained by our analysis. Finally, we provide detailed parameter charts of the range of behavior that each mechanism can produce as coupling strength and walking speed are varied.

Animals↗

Kinetic analysis of duck epsilon-crystallin with L-lactate dehydrogenase activity: determination of kinetic constants and comparison of substrate specificity.

A systematic analysis of the kinetic properties of duck lens epsilon-crystallin with lactate dehydrogenase [LDH, (E.C. 1.1.1.27)] activity was carried out by employing some 19 different alpha-keto acids as substrates for this NADH-dependent LDH-catalyzed reaction. The steady-state Michaelis and catalytic constants (Km, kcat) were determined for a broad range of organic compounds. The results provide important insights regarding the binding and affinity of substrates to active sites of this enzyme crystallin and indicate a great potential for the application of the stable epsilon-crystallin as a catalyst to the synthesis of some important chiral alpha-hydroxyacids in a convenient and efficient way. It is also demonstrated for the first time that in addition to the enzymatic activity of lactate dehydrogenase, duck epsilon-crystallin also possesses the enzymatic activity of malate dehydrogenase.

Animals↗

Molecular analysis and clinical findings in the Spanish Gaucher disease population: putative haplotype of the N370S ancestral chromosome.

Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the lysosomal beta-glucocerebrosidase (GBA) gene. As the disease is particularly prevalent among Ashkenazi Jews, most studies have been carried out on this ethnic group. In the current study, we present a mutation analysis of the GBA gene in Spanish patients together with the clinical findings. We conducted a systematic analysis in 53 unrelated GD patients. The GBA gene was initially scanned for nine previously described mutations by ASO hybridization or restriction analysis after PCR amplification. The remaining unidentified alleles were screened by nonisotopic PCR-SSCP analysis and sequenced. This approach allowed the identification of 101 of 106 GD alleles (95.3%) involving 24 different mutations, 11 of which are described for the first time: G113E (455G-->A), T134P (517A-->C), G389E (1283G-->A), P391L (1289C-->T), N392I (1292A-->T), Y412H (1351T-->G), W(-4)X (108G-->A), Q169X (662C-->T), R257X (886C-->T), 500insT, and IVS5+1G-->T. Most mutations are present in one or few GD chromosomes. However, two mutations, N370S (1226A-->G) and L444P (1448T-->C), are very frequent and account for 66.1% of the total number of alleles. Linkage disequilibrium was detected between these two mutations and an intragenic polymorphism, indicating that expansion of founder alleles occurred in both cases. Analysis of several microsatellite markers close to the GBA gene allowed us to establish the putative haplotype of the ancestral N370S chromosome.

Alleles↗

Isolated noncompaction of the left ventricular myocardium in the adult is an autosomal dominant disorder in the majority of patients.

Isolated noncompaction of the ventricular myocardium (INVM, MIM 300183 and 604169) is a congenital unclassified cardiomyopathy with numerous prominent trabeculations and deep intertrabecular recesses in a hypertrophied and hypokinetic myocardium. Mutations in the G4.5 gene result in a wide spectrum of severe infantile X-linked cardiomyopathic phenotypes including Barth syndrome with dilated cardiomyopathy and INVM. Molecular genetic analysis of INVM has only been performed in pediatric patients. Although adult INVM patients show similar cardiac abnormalities, the influence of genetic factors, especially of mutations in G4.5, is unknown. We analyzed 25 adult INVM patients for the presence of mutations in the G4.5 gene and performed a pedigree analysis of probands. Mutations were not found in the coding sequence or splice sites of G4.5. Systematic analysis of relatives from seven of nine probands showed multiple affected members consistent with an autosomal dominant pattern of inheritance in the majority of cases. We conclude that INVM in the adult is an autosomal dominant disorder rarely caused by mutations in G4.5 and therefore genetically distinct from infantile X-linked cases.

Cardiomyopathies↗

Intravital intestinal videomicroscopy: techniques and experiences.

Intravital videomicroscopy (IVM) of the gastrointestinal (GI) tract is a sophisticated and powerful technique to directly observe the neurologically intact microvasculature of rats in naive and pathological conditions. We combine IVM with other techniques (i.e., vascular ring tension analysis and colorimetric microsphere determination of whole organ blood flow) to develop a strategy for the systematic analysis of the regulation of GI blood flow in healthy animals and in models of systemic sepsis and resuscitated hemorrhagic shock. We also study the molecular biology of the GI tract (enzyme- or radio-linked immunosorbent assays, fluorescent Greiss assay, and immunoblots) to correlate expression and levels of vascular mediators in tissue and arterial, venous, and portal blood with functional activity of the GI microvascular tree. When combined, these techniques develop a picture of gut pathophysiology at the level of the endothelium, vascular smooth muscle cells, and blood cells in the microcirculation. Our work led us to the general hypothesis that altered microcirculatory function in disease states lies primarily at the level of the interface between vascular and tissue physiology, i.e., the endothelial cell. This review focuses on methods and techniques for studying microvascular function, and concludes with focused reviews of pertinent findings.

Animals↗