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Perioperative complications of lumbar instrumentation and fusion in patients with diabetes mellitus.

BACKGROUND CONTEXT: Prior studies have documented an increased complication rate in diabetics treated by lumbar decompression. Despite the assumption that this risk would be exacerbated in larger fusion procedures, a recent study found no such increased risk. PURPOSE: To clarify the perioperative risk for patients with diabetes mellitus undergoing instrumented lumbar fusion as compared with controls. To identify differences, if any exist, between patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes (NIDDM). STUDY DESIGN/SETTING: This is a retrospective case-control study designed to examine the risk of perioperative complications in patients with diabetes mellitus treated by lumbar instrumentation and fusion. This study analyzed 94 diabetic patients and 43 controls treated by posterior lumbar instrumentation and fusion. Outcome was assessed based on the occurrence of perioperative complications. Complications were classified as major or minor. METHODS: Hospital and office records were reviewed for 94 diabetics (51 NIDDM, 43 IDDM) and 43 controls matched for age, sex and procedure with the IDDM group. The groups were compared for demographic characteristics, surgical data, perioperative complications and fusion rate. RESULTS: The NIDDM, IDDM and control groups were equivalent with regard to age, gender, nicotine use, fusion levels, operative time and estimated blood loss. There was a significant difference in complication rate between the NIDDM (53%) and IDDM (56%) groups versus controls (21%). There was a significant increase in complications with multilevel fusion in all groups and with increased operative time in the IDDM group. There was a significantly greater nonunion rate in the NIDDM (22%) and IDDM (26%) groups as compared with controls (5%). CONCLUSIONS: Patients with both IDDM and NIDDM have a significantly increased risk of perioperative complications as compared with controls when treated by lumbar instrumentation and fusion.

Adolescent↗

Multivariate multilevel nonlinear mixed effects models for timber yield predictions.

Nonlinear mixed effects models have become important tools for growth and yield modeling in forestry. To date, applications have concentrated on modeling single growth variables such as tree height or bole volume. Here, we propose multivariate multilevel nonlinear mixed effects models for describing several plot-level timber quantity characteristics simultaneously. We describe how such models can be used to produce future predictions of timber volume (yield). The class of models and methods of estimation and prediction are developed and then illustrated on data from a University of Georgia study of the effects of various site preparation methods on the growth of slash pine (Pinus elliottii Engelm.).

Algorithms↗

Quantitation of daunorubicin and its metabolites by high-performance liquid chromatography with electrochemical detection.

A selective and sensitive high-performance liquid chromatographic method was developed for the separation and quantitation of daunorubicin and its metabolites in serum, plasma, and other biological fluids. Daunorubicin and metabolites in human plasma were injected directly into the high-performance liquid chromatography system via a loop-column to pre-extract the drugs from the plasma, and quantitated against a multilevel calibration curve with adriamycin as the internal standard. The column effluent was monitored with an electrochemical detector at an applied oxidative potential of 0.65 V and by fluorescence. Daunorubicin and four metabolites were separated and characterized by this method. In a blinded evaluation of accuracy and precision, the mean coefficients of variation were 3.8, 3.6 and 9.8% at concentrations of 150, 75 and 15 ng/ml, respectively, and blank samples gave negligible readings. The amperometric sensitivity was greater than achieved by fluorescence detection, and offers an alternative method for quantitation of these compounds. The new method has a limit of detection of less than 2 ng on column, allowing quantitation of less than 10 ng/ml in plasma samples without organic extraction prior to chromatographic analysis.

Chromatography, High Pressure Liquid↗

[Hereditary biochemical diversity in the processes of evolution and individual development].

Results of long-term studies of Russian authors on regularities of expression of hereditary biochemical diversity in evolution and development are reviewed. Primary attention is given to the concepts of genetic monomorphism and genetic stability of population systems, principles of adaptive gene pool structure and optimum genetic diversity, historical and conservation genetics, the concept of the multilevel gene expression, and temporal regulation of ontogenetic functioning of gene clusters coding for enzymes. A universal genetic approach to the problems of evolution and ontogeny is proposed. A population is regarded as a superorganism whose key property is the hierarchic structure of its genetic stability from the stability of monomorphic genes via stability of polymorphic gene frequencies in a multilevel population system to the stability of the total amount of gene diversity in this system. A multicellular organism is also regarded as a developing hierarchical system of populations of cells and genes interacting in a nonrandom fashion. This maintains stability of metabolic processes and is expressed in consistent correlations between monogenic and polygenic morphophysiological characters. Properties of both organisms are determined by the adaptive heterozygosity optimum, the disturbance of which has negative consequences for both individuals and populations. On the basis of these results and the concept on the common nature of evolutionary and ontogenetic processes, the following conclusions are drawn: genetic processes can be either favorable or adverse for developing organisms and populations; the state of genetic processes can be determined by analysis of gene diversity and their deviations from the optimum, taking into account the adaptive gene pool structure; and negative hazardous consequences of extreme external effects at both the individual and population levels can be detected by methods of biochemical genetics in specially planned monitoring programs. Knowledge of normal processes of realization of hereditary information in evolution of populations and in ontogeny opens up new perspectives in detection of unfavorable processes and their correction. This approach proved promising both for preventive and clinical medicine and for exploitation and artificial reproduction of biological resources.

Adaptation, Physiological↗

Expression and tissue-specific assembly of human butyrylcholine esterase in microinjected Xenopus laevis oocytes.

Cholinesterases represent a ubiquitous, polymorphic family of acetylcholine hydrolyzing enzymes. The multileveled tissue-specific heterogeneity which characterizes these enzymes makes the cholinesterases an appropriate model for studying the mechanisms involved in regulating divergent pathways in protein biogenesis. For this purpose, a cDNA coding for human butyrylcholine esterase (BuChE) was subcloned into the SP 6 transcription vector. Synthetic mRNA transcribed from this construct was microninjected into Xenopus laevis oocytes alone, and in conjunction with poly(A)+ RNAs extracted from human brain or muscle. Injected BuChE-mRNA induced the biosynthesis of a protein exhibiting the catalytic activity, substrate specificity, and sensitivity to selective inhibitors characteristic of native human serum BuChE, and clearly distinct from the related enzyme acetylcholinesterase (AChE). The nascent BuChE was reproducibly distributed into low salt-soluble and detergent-extractable pools. Sucrose gradient analysis demonstrated that the nascent human enzyme was capable of limited subunit assembly, appearing as functional dimeric molecules in both of these fractions. Co-injection with brain or muscle-derived mRNAs facilitated higher order oligomeric assembly. Co-injected brain mRNA induced the appearance of tetramers while co-injected muscle mRNA induced the appearance of an array of heavy molecular forms, including a heavy 16 S form. These results indicate that the molecular determinants which distinguish BuChE from AChE are inherent to its primary amino acid sequence and that additional, tissue-specific protein(s) are involved in the modulation of subunit assembly within particular biological milieues.

Animals↗

Adjacent segment stenosis after lumbar fusion requiring second operation.

BACKGROUND: Whereas degeneration of the segment adjacent to lumbar fusion has been often seen on radiographs, a small number of patients with such degenerative changes undergo reoperation. Most follow-up studies have focused on adjacent segment disease based on analysis of radiographs. The present study was conducted to understand the pathology of reoperation cases of adjacent segment disease and factors associated with this condition. Operative indication was consistently restricted to patients with neurological involvement. METHODS: The subjects were 117 patients who had undergone posterior lumbar fusion and were followed for a minimum of 2 years (mean 7 years). Among them, nine patients (7.7%) required a second operation owing to symptomatic adjacent segment disease (stenosis). The reoperation rate was assessed in relation to sex, age, initial pathologic condition, and initial spinal fusion and decompression methods. Data were analyzed in a 2 x 2 cross contingency table using Fisher's exact probability test. A probability of <0.05 was defined as statistically significant. RESULTS: Of the variables examined, only multilevel fusion was associated with a high rate of reoperation with statistical significance (P < 0.04). Two patients (100%) suffering from loss of coronal balance (degenerative scoliosis) also required a second operation. CONCLUSIONS: The reoperation rate of 7.7% for adjacent segment disease in this study was consistent with the prevalence of adjacent segment stenosis in the literature. Given the risk of later occurrence of adjacent segment stenosis following multisegment posterolateral fusion, correction of coronal and sagittal balance, preventive decompression of the adjacent segment, or selective decompression without fusion may have to be considered as an additional or alternative procedure.

Adult↗

Variance components of gingival thickness.

OBJECTIVES: Distinct periodontal phenotypes have been identified by cluster analysis, which is an explorative method with very low external validity. The aim of the present study was to investigate variance components of facial gingival thickness in young adults with mild gingivitis. MATERIAL AND METHODS: Thirty-three non-smoking females, 18-23 years of age, with mild or moderate plaque-induced gingivitis participated. Gingival thickness was measured at every tooth present by use of ultrasound technology to the next 0.1 mm with a lowest measurement of 0.5 mm. Periodontal probing depth and clinical attachment level were measured with a pressure-controlled probe. Gingival bleeding index was assessed after probing on a 0-2 scale, where 1 was slight, and 2 was profuse bleeding on probing. The Silness-Loe plaque index was recorded. Multilevel variance components and random intercept models were built. RESULTS: A 2-level (subject, tooth) variance component model of gingival thickness without any explanatory variable revealed an intercept (mean) of 0.93 +/- 0.02 mm. Subject variation of gingival thickness amounted to 4.2% of the total variance. Addition of tooth- and subject-related covariates to the model revealed, after adjusting for tooth type, an association with periodontal probing depth (estimated coefficient 0.067 +/- 0.025), and considerable association with average bleeding index (-0.395 +/- 0.149) and plaque index (0.125 +/- 0.048). Variation at the tooth level was drastically reduced; subject variation amounted to 5.2%. CONCLUSION: Gingival thickness is mainly associated with tooth-related variables. Bleeding tendency is higher if gingiva is thin. Subject variability related to periodontal phenotype may add to the total variance, however, to a very low extent.

Adolescent↗

Multilevel modelling of medical data.

This tutorial presents an overview of multilevel or hierarchical data modelling and its applications in medicine. A description of the basic model for nested data is given and it is shown how this can be extended to fit flexible models for repeated measures data and more complex structures involving cross-classifications and multiple membership patterns within the software package MLwiN. A variety of response types are covered and both frequentist and Bayesian estimation methods are described.

Algorithms↗

The (mis)estimation of neighborhood effects: causal inference for a practicable social epidemiology.

The resurgence of interest in the effect of neighborhood contexts on health outcomes, motivated by advances in social epidemiology, multilevel theories and sophisticated statistical models, too often fails to confront the enormous methodological problems associated with causal inference. This paper employs the counterfactual causal framework to illuminate fundamental obstacles in the identification, explanation, and usefulness of multilevel neighborhood effect studies. We show that identifying useful independent neighborhood effect parameters, as currently conceptualized with observational data, to be impossible. Along with the development of a dependency-based methodology and theories of social interaction, randomized community trials are advocated as a superior research strategy, one that may help social epidemiology answer the causal questions necessary for remediating disparities and otherwise improving the public's health.

Bias↗

Bioabsorbable anterior lumbar plate fixation in conjunction with anterior interbody fusion cages.

An in vitro biomechanical study was conducted to determine the effects of anterior stabilization on lumbar interbody cage fusion biomechanics in a multilevel human cadaveric lumbar model. Three spine conditions were compared: harvested, bilateral multilevel cages (CAGES), and CAGES with bioabsorbable anterior plates (CBAP), tested under flexion/extension, lateral bending, and axial rotation. Measurements included vertebral motion, applied load, and bending/rotational moments. Application of anterior fixation decreased local motion and increased stiffness of the instrumented levels. Clinically, this spinal stability may serve to promote fusion. Coupled with the bioabsorbability of the plating material, the bioabsorbable anterior lumbar plating system is considered biomechanically advantageous.

Absorbable Implants↗

Direct-push geochemical profiling for assessment of inorganic chemical heterogeneity in aquifers.

Discrete-depth sampling of inorganic groundwater chemistry is essential for a variety of site characterization activities. Although the mobility and rapid sampling capabilities of direct-push techniques have led to their widespread use for evaluating the distribution of organic contaminants, complementary methods for the characterization of spatial variations in geochemical conditions have not been developed. In this study, a direct-push-based approach for high-resolution inorganic chemical profiling was developed at a site where sharp chemical contrasts and iron-reducing conditions had previously been observed. Existing multilevel samplers (MLSs) that span a fining-upward alluvial sequence were used for comparison with the direct-push profiling. Chemical profiles obtained with a conventional direct-push exposed-screen sampler differed from those obtained with an adjacent MLS because of sampler reactivity and mixing with water from previous sampling levels. The sampler was modified by replacing steel sampling components with stainless-steel and heat-treated parts, and adding an adapter that prevents mixing. Profiles obtained with the modified approach were in excellent agreement with those obtained from an adjacent MLS for all constituents and parameters monitored (Cl, NO(3), Fe, Mn, DO, ORP, specific conductance and pH). Interpretations of site redox conditions based on field-measured parameters were supported by laboratory analysis of dissolved Fe. The discrete-depth capability of this approach allows inorganic chemical variations to be described at a level of detail that has rarely been possible. When combined with the mobility afforded by direct-push rigs and on-site methods of chemical analysis, the new approach is well suited for a variety of interactive site-characterization endeavors.

Environmental Monitoring↗

Unplanned childbearing in Kenya: the socio-demographic correlates and the extent of repeatability among women.

Unplanned pregnancies account for a substantial proportion of births in Kenya and can have a variety of negative consequences on individual women, their families, and the society as a whole. This paper examines the correlates of mistimed and unwanted childbearing in Kenya, with special focus on the extent of repetitiveness of these events among women. A multilevel multinomial model is applied to the 1993 Kenya Demographic and Health Survey data. The results show that unplanned childbearing in Kenya is associated with a number of factors, including urban/rural residence, region, ethnicity, maternal education, maternal age, marital status, birth order, length of preceding birth interval, family planning practise, fertility preference and unmet need for family planning. In addition to these factors, women who have experienced an unplanned birth are highly likely to have a repeat occurrence.

Adolescent↗

Are there predictors for the outcome of a PGE1 treatment in peripheral arterial disease with critical limb ischaemia?

BACKGROUND: In a multivariate retrospective analysis was conducted to examine whether and to what extent PGE1 is therapeutically effective and whether there are predictors of response. PATIENTS AND METHODS: The examination included 767 patients (448 women, 319 men) of a mean age of 71.2 years and with peripheral arterial disease (PAD) having existed for 44.7 months on the average. They suffered from critical limb ischaemia (Fontaine's stages III/IV) and showed average tcpO2 values at the instep of 2 mmHg (0 to 15) and average systolic malleolar artery pressures of 18 mmHg (0 to 35 mmHg). Between 1989 and 2001, the patients had received treatments in hospital with i.v. PGE1 doses (2x20 microg or 1x60 microg/day) for an average of 34.2 days (mean of responder- and non-responder group). Patients were called responders when pain had markedly decreased or disappeared, necroses had been reduced or healed completely, and vascular reconstruction, PTA or amputations were not necessary. RESULTS: The clinical analysis showed 82.4% of the patients to be responders and 17.6% to be non-responders. It was demonstrated that the outcome of the therapy was not dependent on the supine or sitting tcpO2, the malleolar artery pressure, the patient's age or sex, the duration of PAD, the number or kind of concomitant diseases, the patient's general condition, the localization and number of vascular occlusions, the kind of prior therapy, or the number of previous amputations, although differences in some of the parameters, while clinically irrelevant, were found to be statistically significant. They are not predictors of the outcome of a PGE, therapy. CONCLUSIONS: Even in extremely bad haemodynamic situations at the beginning of a therapy (malleolar artery pressures from 0 to 35 mmHg, tcpO2 0 to 15 mmHg, multilevel occlusive disease, multiple previous operations and concomitant diseases), PGE, therapies of more than 20 days - on the average 35.6 days (mean of responder group) - duration allow clinically relevant positive results to be achieved.

Age Distribution↗

Long-term results of combined iliac balloon angioplasty and distal surgical revascularization.

Long-term results of combined use of iliac artery percutaneous transluminal angioplasty (PTA) and distal surgical revascularization for the management of multilevel occlusive disease were evaluated over a 12-year period. A total of 79 combined procedures were performed in 75 patients. All patients had tandem occlusive disease, with the inflow lesion felt to preclude a distal revascularization procedure alone. Revascularization was performed for incapacitating claudication in 17 (22%) and limb salvage indications in 62 (78%) cases. A mean resting iliac artery pressure gradient of 29 +/- 11 mmHg pre-PTA was reduced to 0.9 +/- 0.4 post-PTA. Major complications of PTA occurred in five (6%) cases, but four were successfully corrected at the time of the distal surgical procedure without alteration of the operative plan. Infrainguinal operations included 55 femoropopliteal or tibial bypass grafts, 18 femorofemoral grafts, and 6 profundaplasties. Mean follow-up was 43 months. By life table analysis, the 5-year primary patency rate of the distal surgical procedures was 76%; a secondary patency of 88% at 5 years was achieved by various means of reintervention. Mean pretreatment ankle/brachial index of 0.31 +/- 0.14 increased to 0.80 +/- 0.16 after operation (p less than 0.0001). The 5-year limb salvage rate was 90%. There were no operative deaths. We conclude that in carefully selected patients, combined use of iliac PTA and distal surgical reconstruction is effective and durable, safely reducing the extent of surgical intervention while reliably increasing the comprehensiveness of revascularization.

Actuarial Analysis↗

Intraoperative somatosensory evoked potential monitoring during cervical spine corpectomy surgery: experience with 508 cases.

STUDY DESIGN: Retrospective review. OBJECTIVES: To review consecutive cases of cervical spine corpectomy surgery performed with intraoperative somatosensory-evoked potential (SSEP) monitoring. SUMMARY OF BACKGROUND DATA: There is controversy about the utility of SSEP monitoring during anterior cervical spine surgery. There is no study in the literature that has specifically evaluated the utility of SSEP monitoring for cervical spine corpectomy surgery. METHODS: Intraoperative SSEP tracings for 508 patients (average age, 55.7 years; 268 male, 240 female) who underwent anterior cervical fusion with single-level or multilevel corpectomies were reviewed. Intraoperative and postoperative records were analyzed to determine if any new neurologic deficits developed when the patients woke up from anesthesia. RESULTS: The overall incidence of a new postoperative neurologic deficit in this series of patients was 2.4% (11 with nerve root injury, 1 with quadriplegia). The incidence of significant SSEP changes was 5.3% (27 of 508 patients). The most common identifiable cause of SSEP changes was hypotension, and the most common neurologic deficit was deltoid (C5) weakness. One patient had irreversible SSEP changes, and he woke up with new-onset quadriplegia. The calculated sensitivity and specificity of intraoperative SSEP monitoring for detecting impending or resultant intraoperative iatrogenic neurologic injury were 77.1% and 100%, respectively. However, if the isolated nerve root injuries are removed from the analysis, then both the calculated sensitivity and the negative predictive values were 100%. CONCLUSIONS: Intraoperative SSEP monitoring can alert the surgeon to adverse iatrogenic intraoperative events with potential for neurologic injury. Most SSEP signal changes are reversible and do not result in a clinical deficit. Isolated nerve root injury appears to be the most common iatrogenic intraoperative injury during cervical spine corpectomy surgery.

Adult↗

The socio-economic patterning of survey participation and non-response error in a multilevel study of food purchasing behaviour: area- and individual-level characteristics.

OBJECTIVE: To undertake an assessment of survey participation and non-response error in a population-based study that examined the relationship between socio-economic position and food purchasing behaviour. DESIGN AND SETTING: The study was conducted in Brisbane City (Australia) in 2000. The sample was selected using a stratified two-stage cluster design. Respondents were recruited using a range of strategies that attempted to maximise the involvement of persons from disadvantaged backgrounds: respondents were contacted by personal visit and data were collected using home-based face-to-face interviews; multiple call-backs on different days and at different times were used; and a financial gratuity was provided. PARTICIPANTS: Non-institutionalised residents of private dwellings located in 50 small areas that differed in their socio-economic characteristics. RESULTS: Rates of survey participation - measured by non-contacts, exclusions, dropped cases, response rates and completions - were similar across areas, suggesting that residents of socio-economically advantaged and disadvantaged areas were equally likely to be recruited. Individual-level analysis, however, showed that respondents and non-respondents differed significantly in their sociodemographic and food purchasing characteristics: non-respondents were older, less educated and exhibited different purchasing behaviours. Misclassification bias probably accounted for the inconsistent pattern of association between the area- and individual-level results. Estimates of bias due to non-response indicated that although respondents and non-respondents were qualitatively different, the magnitude of error associated with this differential was minimal. CONCLUSIONS: Socio-economic position measured at the individual level is a strong and consistent predictor of survey non-participation. Future studies that set out to examine the relationship between socio-economic position and diet need to adopt sampling strategies and data collection methods that maximise the likelihood of recruiting participants from all points on the socio-economic spectrum, and particularly persons from disadvantaged backgrounds. Study designs that are not sensitive to the difficulties associated with recruiting a socio-economically representative sample are likely to produce biased estimates (underestimates) of socio-economic differences in the dietary outcome being investigated.

Adolescent↗

Community psychology at the crossroads: prospects for interdisciplinary research.

Effective engagement in interdisciplinary work is critical if community psychology is to achieve its promise as a field of ecological inquiry and social action. The purpose of this paper and special issue is to help make the benefits of interdisciplinary community research clearer and to identify and begin to address its challenges. Although some areas of psychology (e.g., biological, cognitive and health) have made substantial interdisciplinary strides in recent decades, progress in community psychology (and related areas) is more modest. In this article we explore the prospects for expanding and improving interdisciplinary community research. Challenges include designs, measures, and analytical frameworks that integrate multiple levels of analysis from individuals through families, organizations, and communities to policy jurisdictions, and the complexities involved in simultaneously bringing together multiple disciplinary collaborators and community partners. Challenges to interdisciplinary collaboration common to all disciplines include the disciplinary nature of academic culture and reward structures, limited funding for interdisciplinary work and uncertainties related to professional identity and marketability. Overcoming these challenges requires a synergy among facilitative factors at the levels of the interdisciplinary project team (e.g., the framing question; embedded relationships; leadership), the investigators (e.g., commitment to new learning; time to invest), and the external context (e.g., physical, administrative, economic and intellectual resources and support for interdisciplinary work). We conclude by identifying several exemplars of effective interdisciplinary collaborations and concrete steps our field can take to enhance our development as a vibrant community-based, multilevel discipline increasingly devoted to interdisciplinary inquiry and action.

Cooperative Behavior↗

Toward designing drug-like libraries: a novel computational approach for prediction of drug feasibility of compounds.

Prediction of the degree of drug-like character in small molecules is of great industrial interest. The major barrier, however, is the lack of a definition for drug-like character. We used the concept of the multilevel chemical compatibility (MLCC) between a compound and a drug library as a measure of the drug-like character of a compound. The rationale is that the local chemical environment of each atom or group of atoms in a compound largely contributes to the stability, toxicity, and metabolism in vivo. A systematic comparison of the local environments within a compound and those within the existing drugs provides a basis for determining whether and how much a compound is drug-like. We applied the MLCC calculations to four test sets: top selling drugs, compounds under biological testing prior to the preclinical test, anticancer drugs, and compounds known to have poor drug-like character. The following conclusions were obtained: (1) A convergent number of unique local structure types were found in the analysis of the library of the existing drugs. It suggests that the current drug library contains about 80% of all the viable types; therefore, discovery of a drug with new local structures is only an event of relatively small probability. (2) The method is highly selective in discerning drug-like compounds: most of the top drugs are predicted to be drug-like, about one-quarter of the biological testing compounds are drug-like, and about one-fifth of the anticancer drugs are drug-like. (3) The method also correctly predicted that none of the known problematic compounds are drug-like. (4) The method is fast enough for computational screening of virtual combinatorial chemistry libraries and databases of available compounds.

Combinatorial Chemistry Techniques↗