Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation.

BACKGROUND: Ovarian tissue cryopreservation has been proven to preserve fertility against gonadotoxic treatments. It has not been clear how this procedure would perform if planned for slowing ovarian aging. OBJECTIVE: This study aimed to determine the feasibility of cryopreserving ovarian tissue to extend reproductive life span and delay menopause by autotransplantation near menopause. STUDY DESIGN: Based on the existing biological data on follicle loss rates, a stochastic model of primordial follicle wastage was developed to determine the years of delay in menopause (denoted by D) by ovarian tissue cryopreservation and transplantation near menopause. Our model accounted for (1) age at ovarian tissue harvest (21-40 years), (2) the amount of ovarian cortex harvested, (3) transplantation of harvested tissues in single vs multiple procedures (fractionation), and (4) posttransplant follicle survival (40% [conservative] vs 80% [improved] vs 100% [ideal or hypothetical]). RESULTS: Our model predicted that, for most women aged <40 years, ovarian tissue cryopreservation and transplantation would result in a significant delay in menopause. The advantage is greater if the follicle loss after transplant can be minimized. As an example, the delay in menopause (D) for a woman with a median ovarian reserve who cryopreserves 25% of her ovarian cortex at the age of 25 years and for whom 40% of follicles survive after transplantation would be approximately 11.8 years, but this extends to 15.5 years if the survival is 80%. As another novel finding, spreading the same amount of tissue to repetitive transplants significantly extends the benefit. For example, for the same 25-year-old woman with a median ovarian reserve, 25% cortex removal, and 40% follicle survival, fractionating the transplants to 3 or 6 procedures would result in the corresponding delay in menopause (D) of 23 or 31 years. The same conditions (3 or 6 procedures) would delay menopause as much as 47 years if posttransplant follicle survival is improved to 80% with modern approaches. An interactive Web tool was created to test all variables and the feasibility of ovarian tissue freezing and transplantation to delay ovarian aging (here). CONCLUSION: Our model predicts that with harvesting at earlier adult ages and better transplant techniques, a significant menopause postponement and, potentially, fertile life span extension can be achieved by ovarian tissue cryopreservation and transplantation in healthy women.

Recapitulating human ovarian aging using random walks.

Mechanism(s) that control whether individual human primordial ovarian follicles (PFs) remain dormant, or begin to grow, are all but unknown. One of our groups has recently shown that activation of the Integrated Stress Response (ISR) pathway can slow follicular granulosa cell proliferation by activating cell cycle checkpoints. Those data suggest that the ISR is active and fluctuates according to local conditions in dormant PFs. Because cell cycle entry of (pre)granulosa cells is required for PF growth activation (PFGA), we propose that rare ISR checkpoint resolution allows individual PFs to begin to grow. Fluctuating ISR activity within individual PFs can be described by a random process. In this article, we model ISR activity of individual PFs by one-dimensional random walks (RWs) and monitor the rate at which simulated checkpoint resolution and thus PFGA threshold crossing occurs. We show that the simultaneous recapitulation of (i) the loss of PFs over time within simulated subjects, and (ii) the timing of PF depletion in populations of simulated subjects equivalent to the distribution of the human age of natural menopause can be produced using this approach. In the RW model, the probability that individual PFs grow is influenced by regionally fluctuating conditions, that over time manifests in the known pattern of PFGA. Considered at the level of the ovary, randomness appears to be a key, purposeful feature of human ovarian aging.

New Insights for Tracking Global and Local Trends in Exposure to Air Pollutants.

Over six million people die prematurely each year from exposure to air pollution. Current air quality metrics insufficiently monitor exposure to air pollutants. This gap hinders the ability of decisionmakers to address the public health impacts of air pollution. To spur new emissions control policies and ensure implemented solutions realize meaningful gains in environmental health, we develop a framework of public-health-focused air quality indicators that quantifies over 200 countries' trends in exposure to particulate matter, ozone, nitrogen oxides, sulfur dioxide, carbon monoxide, and volatile organic compounds. We couple population density to ground-level pollutant concentrations to derive population-weighted exposure metrics that quantify the pollutant levels experienced by the average resident in each country. Our analyses demonstrate that most residents in 171 countries experience pollutant levels exceeding international health guidelines. In addition, we find a negative correlation between temporal trends in ozone and nitrogen oxide concentrations, which─when qualitatively interpreted with a simple atmospheric chemistry box model─can help describe the apparent tradeoff between the mitigation of these two pollutants on local scales. These novel indicators and their applications enable regulators to identify their most critical pollutant exposure trends and allow countries to track the performance of their emission control policies over time.

Estimated Placental Volume and Gestational Age.

OBJECTIVE: The objective of this study was to validate estimated placental volume (EPV) across a range of gestational ages (GAs). STUDY DESIGN: Three hundred sixty-six patients from 2009 to 2011 received ultrasound scans between 11 + 0 and 38 + 6 weeks GA to assess EPV. An EPV versus GA best fit curve was generated and compared with published normative curves of EPV versus GA in a different population. A subanalysis was performed to explore the relationship between EPV and birth weight (BW). RESULTS: Analysis of EPV versus GA revealed a parabolic curve with the following best fit equation: EPV = (0.372 GA - 0.00364 GA2)3. EPV was weakly correlated with BW, and patients with an EPV in the bottom 50th percentile had 2.42 times the odds of having a newborn with a BW in the bottom 50th percentile (95% confidence interval: 1.27-4.68). Microscopic evaluation of two placentas corresponding to the smallest EPV outliers revealed significant placental pathology. CONCLUSION: Placental volume increases throughout gestation and follows a predictable parabolic curve, in agreement with the existing literature. Further validation is required, but EPV may have the potential for clinical utility as a screening tool in a variety of settings.

A multivariate distance-based analytic framework for connectome-wide association studies.

The identification of phenotypic associations in high-dimensional brain connectivity data represents the next frontier in the neuroimaging connectomics era. Exploration of brain-phenotype relationships remains limited by statistical approaches that are computationally intensive, depend on a priori hypotheses, or require stringent correction for multiple comparisons. Here, we propose a computationally efficient, data-driven technique for connectome-wide association studies (CWAS) that provides a comprehensive voxel-wise survey of brain-behavior relationships across the connectome; the approach identifies voxels whose whole-brain connectivity patterns vary significantly with a phenotypic variable. Using resting state fMRI data, we demonstrate the utility of our analytic framework by identifying significant connectivity-phenotype relationships for full-scale IQ and assessing their overlap with existent neuroimaging findings, as synthesized by openly available automated meta-analysis (www.neurosynth.org). The results appeared to be robust to the removal of nuisance covariates (i.e., mean connectivity, global signal, and motion) and varying brain resolution (i.e., voxelwise results are highly similar to results using 800 parcellations). We show that CWAS findings can be used to guide subsequent seed-based correlation analyses. Finally, we demonstrate the applicability of the approach by examining CWAS for three additional datasets, each encompassing a distinct phenotypic variable: neurotypical development, Attention-Deficit/Hyperactivity Disorder diagnostic status, and L-DOPA pharmacological manipulation. For each phenotype, our approach to CWAS identified distinct connectome-wide association profiles, not previously attainable in a single study utilizing traditional univariate approaches. As a computationally efficient, extensible, and scalable method, our CWAS framework can accelerate the discovery of brain-behavior relationships in the connectome.

The effects of edema and self-adherent wrap on the work of flexion in a cadaveric hand.

PURPOSE: Early motion protocols after flexor tendon repair often require hand therapy in edematous digits. Self-adherent wraps are used in the postoperative period to reduce edema. The purpose of this study was to determine whether the presence of a self-adherent wrap affected the work of flexion during early motion protocols. METHODS: In an unpreserved cadaveric hand, the flexor digitorum profundus and flexor pollicis longus tendons were identified and attached to a tensile testing machine to measure work of flexion (WoF). We simulated subcutaneous edema by injecting normal saline into the digits. Moderate and severe edema was simulated by 10% and 20% increases in circumference of the digits, respectively. We evaluated 2 commonly used products: 2.5-cm Coban self-adherent wrap (3M, St. Paul, MN) and 2.5-cm Co-Wrap cohesive bandage (Hartmann, Rock Hill, SC). Statistical analyses include analysis of variance, 95% confidence intervals for average responses, and graphical display of both data and model predictions. RESULTS: In digits without edema or wraps, WoF ranged from 0.0114 J (small finger) to 0.0710 J (thumb). Without wraps, simulated moderate and severe edema was predicted to increase WoF by an average of 23% and 71%, respectively. Application of self-adherent wrap increased WoF values significantly in all digits. In the majority of conditions tested, application of self-adherent wrap increased WoF more significantly than moderate edema did. The effects of edema and self-adherent wrap were additive, producing WoF values 4 times the baseline values. CONCLUSIONS: Edema and self-adherent wrap increased WoF in this model. Therapists and surgeons should be aware of increased stress placed on tendons when early motion protocols are initiated in the presence of edema and self-adherent wrap. CLINICAL RELEVANCE: We recommend removal of self-adherent wrap before starting a therapy session.

Cone-beam reconstruction for the two-circles-plus-one-line trajectory.

The Kodak Image Station In-Vivo FX has an x-ray module with cone-beam configuration for radiographic imaging but lacks the functionality of tomography. To introduce x-ray tomography into the system, we choose the two-circles-plus-one-line trajectory by mounting one translation motor and one rotation motor. We establish a reconstruction algorithm by applying the M-line reconstruction method. Numerical studies and preliminary physical phantom experiment demonstrate the feasibility of the proposed design and reconstruction algorithm.

Reference regions for beat-to-beat ECG data.

The QT interval is regarded as an important biomarker for the assessment of arrhythmia liability, and evidence of QT prolongation has led to the withdrawal and relabeling of numerous compounds. Traditional methods of assessing QT prolongation correct the QT interval for the length of the RR interval (which varies inversely with heart-rate) in a variety of ways. These methods often disagree with each other and do not take into account changes in autonomic state. Correcting the QT interval for RR reduces a bivariate observation (RR, QT) to a univariate observation (QTc). The development of automatic electrocardiogram (ECG) signal acquisition systems has made it possible to collect continuous (so called 'beat-to-beat') ECG data. ECG data collected prior to administration of a compound allow us to define a region for (RR, QT) values that encompasses typical activity. Such reference regions are used in clinical applications to define the 'normal' region of clinical or laboratory measurements. This paper motivates the need for reference regions of (RR, QT) values from beat-to-beat ECG data, and describes a way of constructing these. We introduce a measure of agreement between two reference regions that points to the reliability of 12-lead digital Holter data. We discuss the use of reference regions in establishing baselines for ECG parameters to assist in the evaluation of cardiac risk and illustrate using data from two methodological studies.

Accelerated solvent extraction of lignin from Aleurites moluccana (Candlenut) nutshells.

Lignin from candlenut shells was isolated using an ethanol-water accelerated solvent extraction method. Yields (based on Klason lignin) increased from about 14 to 33% as temperature increased from 100 to 195 °C and were also influenced by the amount of aqueous acid used to precipitate lignin from the extraction liquor. These yields were higher than could be obtained using a conventional dioxane-water acidolysis method. The resulting lignin was characterized by IR, 31P NMR, and 1H-13C HMQC NMR spectroscopic techniques. The lignin contained predominantly guaiacyl units, and both the total hydroxyl group content and phenolic hydroxyl group content were high.

Quantitative assessment of tissue biomarkers and construction of a model to predict outcome in breast cancer using multiple imputation.

Missing data pose one of the greatest challenges in the rigorous evaluation of biomarkers. The limited availability of specimens with complete clinical annotation and quality biomaterial often leads to underpowered studies. Tissue microarray studies, for example, may be further handicapped by the loss of data points because of unevaluable staining, core loss, or the lack of tumor in the histospot. This paper presents a novel approach to these common problems in the context of a tissue protein biomarker analysis in a cohort of patients with breast cancer. Our analysis develops techniques based on multiple imputation to address the missing value problem. We first select markers using a training cohort, identifying a small subset of protein expression levels that are most useful in predicting patient survival. The best model is obtained by including both protein markers (including COX6C, GATA3, NAT1, and ESR1) and lymph node status. The use of either lymph node status or the four protein expression levels provides similar improvements in goodness-of-fit, with both significantly better than a baseline clinical model. Using the same multiple imputation strategy, we then validate the results out-of-sample on a larger independent cohort. Our approach of integrating multiple imputation with each stage of the analysis serves as an example that may be replicated or adapted in future studies with missing values.

The assessment of cervical foramina with oblique radiographs: the effect of film angle on foraminal area.

STUDY DESIGN: Radiographic evaluation of cadaveric cervical spine specimens. OBJECTIVE: Assess reliability and reproducibility of foraminal dimensions obtained from cervical radiographs of varying obliquity and determine optimal angles for visualizing foramina at each cervical spine level. SUMMARY OF BACKGROUND DATA: Oblique radiographs may be considered to assess cervical foraminal dimensions and are generally obtained 45 degrees from the anteroposterior (AP) orientation. Previous reports have suggested that foraminal area observed on these radiographs may be influenced by changes in obliquity so that certain film angles may be better suited for accurately assessing foramen size, depending on which level is being evaluated. METHODS: Radiographs of 4 human cadaveric cervical spines were obtained at 5-degree increments from 20 to 70 degrees relative to AP orientation, using both left and right sides of each specimen. Foraminal area was estimated by measuring height and width of each foramen and also with a freehand area measurement tool. Reliabilities of both methods were calculated. At each level, foraminal area was plotted against film angle and quadratic best-fit curves were used to determine the maximum area observed and the optimal angle of obliquity for assessment. RESULTS: Assessment of foraminal area using the height and width values was associated with good interobserver reliability, whereas the freehand method exhibited excellent reliability. The optimal film angles for calculating foraminal area increased from 46.3 degrees for C2-C3 to 56.1 degrees for C7-T1. The ideal film angle that minimized the overall error of measurement across the entire cervical spine was estimated to be 52.4 degrees. CONCLUSIONS: Optimal angles for visualizing lower cervical foramina are larger than those for upper cervical spine. To minimize overall loss of foraminal area throughout the entire cervical spine, oblique cervical radiographs should be obtained at an angle of approximately 52 degrees from the AP orientation.

Macrophages directly contribute to the exaggerated inflammatory response in cystic fibrosis transmembrane conductance regulator-/- mice.

Pulmonary infection with an exaggerated inflammatory response is the major cause of morbidity and mortality in cystic fibrosis (CF). The objective of this study was to determine whether differences in the innate immune system underlie the exaggerated immune response in CF. We established a model that recapitulates the exaggerated immune response in a CF mouse model by exposure to Pseudomonas aeruginosa LPS and assessed the pulmonary cellular and cytokine responses of wild-type (WT) and CF mice. Compared with WT mice, CF mice had increased numbers of neutrophils and increased proinflammatory cytokines in their bronchoalveolar lavage fluid after LPS exposure. Based on the increased levels of IL-1alpha, IL-6, granulocyte colony-stimulating factor (G-CSF), and keratinocyte chemoattractant, all of which are known to be produced by macrophages, we tested whether two populations of macrophages, bone marrow-derived macrophages and alveolar macrophages, directly contribute to the elevated cytokine response of CF mice to LPS. After in vitro stimulation of bone marrow-derived macrophages and alveolar macrophages with LPS, IL-1alpha, IL-6, G-CSF, and monocyte chemoattractant protein-1 were higher in CF compared with WT cell supernatants. Quantitative analyses for IL-6 and keratinocyte chemoattractant revealed that LPS-stimulated CF macrophages have higher mRNA and intracellular protein levels compared with WT macrophages. Our data support the hypothesis that macrophages play a role in the exuberant cytokine production and secretion that characterizes CF, suggesting that the macrophage response may be an important therapeutic target for decreasing the morbidity of CF lung disease.

A fast Bayesian change point analysis for the segmentation of microarray data.

MOTIVATION: The ability to detect regions of genetic alteration is of great importance in cancer research. These alterations can take the form of large chromosomal gains and losses as well as smaller amplifications and deletions. The detection of such regions allows researchers to identify genes involved in cancer progression, and to fully understand differences between cancer and non-cancer tissue. The Bayesian method proposed by Barry and Hartigan is well suited for the analysis of such change point problems. In our previous article we introduced the R package bcp (Bayesian change point), an MCMC implementation of Barry and Hartigan's method. In a simulation study and real data examples, bcp is shown to both accurately detect change points and estimate segment means. Earlier versions of bcp (prior to 2.0) are O(n(2)) in speed and O(n) in memory (where n is the number of observations), and run in approximately 45 min for a sequence of length 10 000. With the high resolution of newer microarrays, the number of computations in the O(n(2)) algorithm is prohibitively time-intensive. RESULTS: We present a new implementation of the Bayesian change point method that is O(n) in both speed and memory; bcp 2.1 runs in approximately 45 s on a single processor with a sequence of length 10,000--a tremendous speed gain. Further speed improvements are possible using parallel computing, supported in bcp via NetWorkSpaces. In simulated and real microarray data from the literature, bcp is shown to quickly and accurately detect aberrations of varying width and magnitude. AVAILABILITY: The R package bcp is available on CRAN (R Development Core Team, 2008). The O(n) version is available in version 2.0 or higher, with support for NetWorkSpaces in versions 2.1 and higher.

Quantifying the effects of degeneration and other patient factors on lumbar segmental range of motion using multivariate analysis.

STUDY DESIGN: Retrospective review and multivariate analysis. OBJECTIVES: Assess lumbar spine segmental range of motion (ROM) with flexion/extension (F/E) radiographs and determine the relation to clinical variables. SUMMARY OF BACKGROUND DATA: Prior studies have investigated the roles of age and degeneration on lumbar segmental ROM only using univariate analyses. Multivariate analyses are also required to differentiate the multiple factors that may affect ROM and quantify their relative effects. METHODS: Radiographs of 258 patients were analyzed, including 137 females and 121 males with ages ranging from 18 to 92 years. Segmental ROM and Kellgren score (KS) of degeneration were assessed for L1-S1. Multivariate regression analyses were performed for each level. Predicting variables evaluated were: (1) KS at the level of interest, (2) KS at the level above, (3) KS at the level below, (4) age, (5) gender, (6) weight, (7) height, (8) body mass index (BMI), and (9) smoking. Significance was defined as P < 0.05. RESULTS: Interobserver reliabilities for assessing KS (ICC 0.70) and segmental ROM (ICC 0.80) were good to excellent. In the multivariate analyses, age had a significant negative association with ROM at L1-L2, L2-L3, L3-L4, and L4-L5. BMI had a significant negative association with ROM at L2-L3, L3-L4, and L4-L5. KS at the level of interest had significant negative association with ROM only at L5-S1. KS at adjacent levels, gender, weight, height, and smoking did not have a significant association with ROM at any level. CONCLUSION: The results of this study provide the clinician with insight into factors that influence segmental lumbar ROM. Age was the strongest statistical predictor of ROM and was associated with declining ROM, amounting to an approximate 3 degrees decrease in total sagittal lumbar ROM in the superior 4 segments every 10 years. BMI was another factor associated with lumbar ROM. Degeneration was a significant predictor of ROM only at L5-S1.

Evaluation of a modified protocol for selective laser trabeculoplasty.

PURPOSE: To compare the intraocular pressure (IOP) response to a modified protocol for selective laser trabeculoplasty (SLT) to standard protocols for SLT and argon laser trabeculoplasty (ALT). MATERIALS AND METHODS: A retrospective study of 318 eyes of 284 patients diagnosed with either primary open angle, pigmentary or pseudoexfoliation glaucoma who underwent laser trabeculoplasty from September 1997 to September 2005. One hundred and two patients, who underwent a modified SLT protocol with 100 overlapping laser spots over 180 degrees of trabecular meshwork were compared with 89 patients who received SLT with 100 nonoverlapping spots over 360 degrees and another 127 patients who received ALT with 50 spots over 180 degrees. IOPs were measured at baseline and postoperatively at 1 hour, 6 weeks, 4 months, and 14 months. Regression models, based on the observed data, were used to predict the fall in IOP in the 3 groups, controlling for differences in baseline pressure. RESULTS: The IOP response to overlapping SLT was significantly worse than to nonoverlapping SLT or ALT, both of which had similar responses. Baseline IOP was the only preoperative factor that predicted response to ALT (P<0.0001) and nonoverlapping SLT (P=0.0019) at all follow-up times. There were no statistically significant predictive factors for IOP reduction in the overlapping SLT group. CONCLUSIONS: Overlapping application of SLT results in a poorer IOP response compared with ALT and nonoverlapping SLT.

Quantifying the effects of age, gender, degeneration, and adjacent level degeneration on cervical spine range of motion using multivariate analyses.

STUDY DESIGN: Retrospective review and multivariate analysis. OBJECTIVE: Assess cervical spine segmental range of motion (ROM) with flexion/extension (F/E) radiographs and determine the relation to clinical variables. SUMMARY OF BACKGROUND DATA: Previous studies investigated the roles of age and degeneration on cervical ROM with univariate analyses. Multivariate analyses are required to account for multiple factors that may affect ROM and quantify their relative effects. METHODS: Radiographs of 195 patients were analyzed, including 133 females and 62 males with ages ranging from 15 to 93 years. Segmental ROM and Kellgren score (KS) of degeneration were assessed for C2-C7. Patient's age and gender were documented. Multivariate analyses were performed for each level. Independent variables evaluated were: (1) KS at the level of interest, (2) KS at the level above, (3) KS at the level below, (4) age, and (5) gender. Significance was defined as P < 0.05. RESULTS: Interobserver reliabilities for assessing KS (intraclass correlation coefficient 0.81) and segmental ROM (intraclass correlation coefficient 0.72) were good to excellent. Age had a significant negative association with ROM at C2-C3, C3-C4, C4-C5, and C5-C6. KS at the level of interest had a significant negative association with ROM at C2-C3, C3-C4, C4-C5, C5-C6, and C6-C7. KS at the inferior segment had a significant positive association with ROM at C2-C3, C3-C4, and C4-C5. Gender had a significant association with ROM only at C2-C3. CONCLUSION: Age was associated with declining ROM independent of degeneration, amounting to a 5 degrees decrease in subaxial cervical ROM every 10 years. Degeneration was also associated with ROM. For every point increase in KS at a given level, there was an associated 1.2 degrees decrease in ROM at that level, and a 0.8 degrees increase in ROM at the level above. These results provide a framework with which to counsel patients about cervical ROM and a benchmark from which procedure specific changes can be compared.

Surgical management of pseudophakic retinal detachments: a meta-analysis.

PURPOSE: To compare the success of pars plana vitrectomy (PPV) versus scleral buckle (SB) in the management of uncomplicated pseudophakic retinal detachments (RDs). DESIGN: Meta-analysis of published studies from 1966 to 2004 regarding surgical treatment of pseudophakic RDs. PARTICIPANTS: Two thousand two hundred thirty eyes: 1579 operated by SB, 457 by PPV, and 194 by the combined method of PPV and SB. METHODS: We compared reattachment and functional success rates after 3 commonly practiced surgical interventions for pseudophakic RDs: PPV, SB, and the combined method. Twelve hundred thirty-two articles were retrieved from Medline and by cross-reference searches. Articles with sufficient data on preoperative evaluation, applied surgical technique, and anatomical and functional success rates were included in this analysis. Articles regarding complex pseudophakic RDs, treatment by laser or pneumatic retinopexy, studies with indistinguishable treatment outcomes from phakic and pseudophakic RDs, or reviews without original data were excluded. MAIN OUTCOME MEASURES: Anatomical success rates after initial surgical intervention and after reoperation(s) for primary failures, and best or final visual outcome at the end of follow-up. RESULTS: Of 1232 papers, 29 matched inclusion criteria. After controlling for variation between study characteristics, PPV and the combined method resulted in higher initial reattachment rates (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.07-2.68, and OR, 3.54; 95% CI, 1.57-7.97, respectively) as compared with SB. The differences between the procedures persisted for final reattachment outcome despite reoperation for primary failures. Final visual outcome also was found to depend on the choice of primary surgical intervention. After controlling for differences in the study characteristics, the probability of visual improvement was higher after PPV (OR, 2.34; 95% CI, 1.58-3.46) or the combined method (OR, 11.52; 95% CI, 4.42-30.04) as compared with SB. CONCLUSIONS: A meta-analysis of published literature implies that PPV with or without SB is more likely to achieve a favorable anatomical and visual outcome than conventional SB alone in uncomplicated pseudophakic RDs. However, the inherent limitations of differing study protocols, quality of included studies, and publication bias in a pooled analysis should be recognized.

The effect of Gonioscopy on keratometry and corneal surface topography.

BACKGROUND: Biometric procedures such as keratometry performed shortly after contact procedures like gonioscopy and applanation tonometry could affect the validity of the measurement. This study was conducted to understand the short-term effect of gonioscopy on corneal curvature measurements and surface topography based Simulated Keratometry and whether this would alter the power of an intraocular lens implant calculated using post-gonioscopy measurements. We further compared the effect of the 2-mirror (Goldmann) and the 4-mirror (Sussman) Gonioscopes. METHODS: A prospective clinic-based self-controlled comparative study. 198 eyes of 99 patients, above 50 years of age, were studied. Exclusion criteria included documented dry eye, history of ocular surgery or trauma, diabetes mellitus and connective tissue disorders. Auto-Keratometry and corneal topography measurements were obtained at baseline and at three follow-up times - within the first 5 minutes, between the 10th-15th minute and between the 20th-25th minute after intervention. One eye was randomized for intervention with the 2-mirror gonioscope and the other underwent the 4-mirror after baseline measurements. t-tests were used to examine differences between interventions and between the measurement methods. The sample size was calculated using an estimate of clinically significant lens implant power changes based on the SRK-II formula. RESULTS: Clinically and statistically significant steepening was observed in the first 5 minutes and in the 10-15 minute interval using topography-based Sim K. These changes were not present with the Auto-Keratometer measurements. Although changes from baseline were noted between 20 and 25 minutes topographically, these were not clinically or statistically significant. There was no significant difference between the two types of gonioscopes. There was greater variability in the changes from baseline using the topography-based Sim K readings. CONCLUSION: Reversible steepening of the central corneal surface is produced by the act of gonioscopy as measured by Sim K, whereas no significant differences were present with Auto-K measurements. The type of Gonioscope used does not appear to influence these results. If topographically derived Sim K is used to calculate the power of the intraocular lens implant, we recommend waiting a minimum of 20 minutes before measuring the corneal curvature after gonioscopy with either Goldmann or Sussman contact lenses.

Lumbar total disc arthroplasty utilizing the ProDisc prosthesis in smokers versus nonsmokers: a prospective study with 2-year minimum follow-up.

STUDY DESIGN: Prospective nonrandomized clinical series. OBJECTIVES: To evaluate the efficacy of ProDisc lumbar artificial disc replacement (ADR) in smokers versus nonsmokers. SUMMARY OF BACKGROUND DATA: Smoking is a negative predictor in fusion surgery. To date, a prospective study of the treatment of incapacitating discogenic low back pain using ADR in smokers versus nonsmokers has not been described. METHODS: A prospective analysis was performed on 104 patients with disabling discogenic low back pain treated with single-level lumbar ProDisc total disc arthroplasty. Smokers and nonsmokers were assessed before surgery and after surgery using patient satisfaction, Oswestry, and Visual Analog Scores. Additionally, preoperative and postoperative neurologic, radiographic, and pain medication assessments were performed at similar postoperative intervals. RESULTS: Oswestry, Visual Analog Scores, and patient satisfaction scores revealed statistical improvement beginning 3 months after surgery and were maintained at minimum 2-year follow-up. Patient satisfaction scores were higher in smokers (94%) than in nonsmokers (87%) at 2-year follow-up (P = 0.07). Radiographic analysis revealed an affected disc height increase from 4 mm to 13 mm (P < 0.05) and an affected disc motion from 3 degrees to 7 degrees (P < 0.05). No cases of loosening, dislodgment, mechanical failure, infection, or fusion of the affected segment occurred. CONCLUSIONS: The results of our study indicate that smokers do equally well compared with nonsmokers when ProDisc ADR is used in the treatment of debilitating lumbar spondylosis. Patient outcome and radiographic scores showed significant improvement compared with preoperative levels. Although not evident in our series, additional surveillance for intraoperative and postoperative vascular spasm and occlusion may be warranted in smokers.

Treatment of symptomatic adjacent-segment degeneration after lumbar fusion with total disc arthroplasty by using the prodisc prosthesis: a prospective study with 2-year minimum follow up.

OBJECT: The authors conducted a prospective longitudinal study to assess the efficacy of ProDisc arthroplasty in patients in whom symptomatic adjacent-segment degeneration has developed after remote lumbar fusion. The follow-up period was a minimum of 2 years. METHODS: The 20 patients in this study ranged in age from 18 to 67 years. They presented with disabling adjacent-level discogenic low-back pain with or without L1-S1 radicular pain. Patients with radiographic evidence of circumferential spinal stenosis or facet joint degeneration had been excluded. Patients were assessed preoperatively and postoperatively at 3, 6, 12, and 24 months. Eighteen patients (90%) fulfilled all follow-up criteria. The median age of all patients was 50 years. Statistical improvements in visual analog scale, Oswestry Disability Index, and patient satisfaction scores were documented 3 months after arthroplasty. These improvements remained at the 24-month follow-up examinations. Patient satisfaction rates were 86% at 24 months. Radicular pain was also significantly decreased. No additional surgeries were necessary at affected or unaffected levels. CONCLUSIONS: Analysis of early results indicates that ProDisc lumbar total disc arthroplasty is an efficacious treatment for symptomatic adjacent-segment lumbar discogenic low-back pain following remote fusion. Significant improvements in patient satisfaction and disability scores were observed by 3 months postoperatively and were maintained at the 2-year follow-up examination. No device-related complications occurred. Patients should be screened carefully for evidence of facet joint impingement/degeneration, hardware-induced pain, and/or nonunion at prior fusion levels before undergoing disc replacement surgery.