Early Cholecystectomy in Patients with Sickle Cell Disease with Uncomplicated Cholelithiasis Is Associated with Better Outcomes.

BACKGROUND: Up to 85% of patients with sickle cell disease (SCD) will develop gallstones by their third decade. Cholecystectomy is the most commonly performed procedure in these patients. Cholecystectomy is recommended for patients with SCD with symptomatic cholelithiasis and leads to lower morbidity. No contemporary large studies have evaluated this recommendation or associated clinical outcomes. This study evaluates clinical outcomes after cholecystectomy in patients with SCD and cholelithiasis with specific advanced clinical presentations. STUDY DESIGN: The Nationwide Inpatient Sample was queried for patients with SCD and gallbladder disease between 2006 and 2015. Patients were divided into groups based on their disease presentation, including uncomplicated cholelithiasis, acute and chronic cholecystitis, and gallstone pancreatitis. Clinical outcomes associated with disease presentation were analyzed. Statistical analysis was performed using the Student's t -test, chi-square test, ANOVA, and logistic regression. RESULTS: There were 6,662 patients with SCD who presented with cholelithiasis. Median age was 20 (interquartile range 16 to 34) years and 54% were female patients. Cholecystectomy was performed in 1,779 patients with SCD with the most common indication being chronic cholecystitis (44%), followed by uncomplicated cholelithiasis (27%), acute cholecystitis (21%), and choledocholithiasis or gallstone pancreatitis (8%). On multivariable regression, advanced clinical presentation was the strongest predictor of perioperative vaso-occlusive crisis, which was the most common complication. Patients undergoing cholecystectomy for uncomplicated cholelithiasis were at lower risk than those with acute cholecystitis (odds ratio [OR] 2.37; 95% CI 1.64 to 3.41), chronic cholecystitis (OR 1.74; 95% CI 1.26 to 2.4), and choledocholithiasis or gallstone pancreatitis (OR 2.24; 95% CI 1.41 to 3.57). CONCLUSIONS: Seventy-three percent of patients with SCD have advanced clinical presentation at the time of their cholecystectomy. After cholecystectomy, perioperative vaso-occlusive events were significantly increased in patients with advanced clinical presentation. These data support screening abdominal ultrasounds and early cholecystectomy for cholelithiasis in patients with SCD.

Changes in perceived stress and food or housing insecurity associated with COVID-19 in doctor of pharmacy students: A pre- and current- COVID-19 survey.

Background: The novel coronavirus 2019 (COVID-19) pandemic impacted everyday life for most individuals, including students. Unique COVID-19 stressors among students may include virtual learning, mental stress, and being socially distanced from classmates. Studies examining the impact of COVID-19 on stress and lifestyle changes among pharmacy students are limited. Objective: The primary purpose of this study was to compare stress and food or housing insecurity changes associated with COVID-19 in U.S. Doctor of Pharmacy (PharmD) students pre-COVID vs. during-COVID. Methods: A 23-item survey was administered via Qualtrics® to multiple PharmD programs across the U.S. in pre-COVID-19 (spring 2019) and during-COVID-19 (spring 2021). Participants were recruited via e-mail. The survey included questions related to demographics, lifestyle (sleep, exercise, work hours, extracurricular activities), and food and housing insecurities. The survey also included a validated instrument to measure stress (Cohen-Perceived Stress Scale). Results from 2021 were compared to a similar national survey serendipitously administered prior to COVID-19 in Spring 2019. Results: Pre- and COVID-19 analytical cohorts included 278 and 138 participants, respectively. While pre-COVID-19 students were slightly older (29.9 ± 4.7 vs. 27.7 ± 4.2, p ≤0.001), relative to COVID-19 students, other demographic factors were similar. No significant difference was observed in reported stress levels (PSS = 20.0 ± 6.3 vs. 19.7 ± 6.2, p = 0.610) between time periods. Significant differences in food (53.2% vs. 51.4%, p = 0.731) and housing (45.0% vs. 47.1%, p = 0.680) insecurity were also not seen. Conclusions: These findings highlight that PharmD students' perceived stress and food and housing insecurities due to COVID-19 may have been minimal. Additional studies on pharmacy students should be conducted to validate these results. These results may help inform policymakers and stakeholders during the early stages of any future pandemics.

Effectiveness of Baduanjin (a Type of Qigong) on Physical, Cognitive, and Mental Health Outcomes: A Comprehensive Review.

Objectives: The aim of this study is to comprehensively review empirical evidence on the effectiveness of Baduanjin exercise, one type of mind-body focused qigong exercise, on individuals' physical, cognitive, and mental well-being; outline potential mechanisms; and, suggest potential implication strategies for using Baduanjin in clinical practices and for future research. Methods: Recent randomized-controlled studies and systematic reviews/meta-analyses published in English were searched in PubMed, PsycINFO, and Scopus up to July 2022. The search terms include Baduanjin and sleep, chronic illness, cognition, mental health, etc. We only selected papers that specifically studied the health effects of Baduanjin, excluding those that involved other forms of Qigong or other traditional Chinese medical practices. Since many RCT studies have already been included in the review papers that we selected, only those not covered in the review papers were selected to avoid repetition. Results: 19 recent randomized-controlled studies and 8 systematic reviews were identified. In general, the effectiveness of Baduanjin exercise on individuals' physical, cognitive, and mental health is evident. Baduanjin has proven to be effective in improving sleep quality, including reducing difficulties in getting asleep and reducing daytime sleepiness. It also reduces fatigue and improves the quality of life for patients with other physical health issues, such as cancer, musculoskeletal pain, and chronic illnesses. The effectiveness of Baduanjin exercise is also evident in cognition, improving executive functions, and slowing down age-related cognitive deterioration. Similarly, Baduanjin alleviates various types of mental illnesses, increases patients' social competence, and enhances emotional regulation. Conclusion: There is initial evidence on the safety and efficacy of Baduanjin in improving individuals' various aspects of health and well-being, suggesting that Baduanjin may serve as an effective adjunct to conventional treatments for a variety of clinical health benefits. More research is needed to confirm the efficacy and safety of Baduanjin in other non-Chinese ethnic populations.

Validation of the AO Spine Thoracolumbar Injury Classification System Treatment Algorithm: Should it be used to Guide Fracture Management?

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: To determine how historical management of thoracolumbar spine injuries compares to the recently proposed AO Spine Thoracolumbar Injury Classification System treatment algorithm. SUMMARY OF BACKGROUND DATA: Classifications of the thoracolumbar spine are not uncommon. The frequent advent of new classifications is typically due to previous classifications being primarily descriptive or unreliable. Thus, AO Spine created a classification with an associated treatment algorithm to guide injury classification and management. METHODS: Thoracolumbar spine injuries were retrospectively identified from a prospectively collected spine trauma database at a single, urban, academic medical center during the years 2006 to 2021. Each injury was classified and assigned points based on the AO Spine Thoracolumbar Injury Classification System injury severity score. Patients were grouped into scores of 3 or less (preferred initial conservative treatment) and greater than 6 (preferred initial surgical intervention). Either operative or non-operative treatment was considered appropriate for injury severity scores of 4 or 5. RESULTS: A total of 815 patients (TL AOSIS 0-3: 486, TL AOSIS 4-5: 150, TL AOSIS 6+: 179) met inclusion status. Injury severity scores of 0-3 were more likely to undergo non-operative management compared to scores of 4-5 or 6+ (99.0% vs. 74.7% vs. 13.4%, P <0.001). Thus, guideline congruent treatment was 99.0%, 100%, and 86.6%, respectively ( P <0.001). Most injuries determined to be a 4 or 5 were treated non-operatively (74.7%). Based on the treatment algorithm, 97.5% of patients who received operative treatment and 96.1% who received non-operative treatment were managed in accordance with the algorithm. Of the 29 patients who did not receive algorithm congruent treatment, 5 (17.2%) were treated surgically. CONCLUSIONS: A retrospective review of thoracolumbar spine injuries at our urban academic medical center identified that patients are historically treated in accordance with the proposed AO Spine Thoracolumbar Injury Classification System treatment algorithm.

Comparing Posterior Lumbar Decompression and Fusion and Transforaminal Lumbar Interbody Fusion in Lumbar Degenerative Spondylolisthesis as Assessed by the CARDS Classification System.

OBJECTIVE: In a retrospective cohort study, we compared the outcomes among clinical and radiographic degenerative spondylolisthesis (CARDS) subtypes for patients undergoing posterior lumbar decompression and fusion (PLDF) or transforaminal lumbar interbody fusion (TLIF) and evaluated the CARDS system as a tool to guide clinical decisions regarding the treatment of degenerative spondylolisthesis (DS). METHODS: Patients undergoing PLDF or TLIF for DS from 2010 to 2020 were identified. The patients were grouped by the preoperative CARDS classification. Multivariate analysis was used to determine the effects of the treatment approach on the 1-year patient-reported outcome measures (PROMs) and 90-day surgical outcomes. RESULTS: A total of 1056 patients were included: 148 patients with type A DS, 323 with type B, 525 with type C, and 60 with type D. Patients with CARDS types A and C who underwent PLDF experienced a longer length of stay and were less likely to be discharged home. No differences were found in the incidence of revisions, complications, or readmissions between the surgical approaches. Patients with CARDS type A undergoing PLDF were less likely to achieve a minimal clinically important difference for back pain (36.8% vs. 76.7%; P = 0.013). No other significant differences were found in the PROMs among the CARDS subtypes. TLIF independently predicted for better leg pain improvement using the visual analog scale at 1 year of follow-up (ß = -2.92; P = 0.017) for patients with CARDS type A. Multivariable analysis demonstrated no significant differences in PROMs by surgical approach among the other CARDS subtypes. CONCLUSIONS: Patients with disc space collapse and endplate apposition (CARDS type A) appear to benefit from TLIF. However, patients with lumbar spondylolisthesis without disc space collapse or kyphotic angulation (CARDS types B and C) showed no benefit from additional interbody placement.

Predictors of Completed Suicides Among Emergency Department Visits for Attempted Suicides.

BACKGROUND: The objective of this study was to identify predictors of mortality among patients presenting to the emergency department (ED) with attempted suicides. METHODS: We analyzed data on emergency department (ED) visits for attempted suicides from the Nationwide Emergency Department Sample (NEDS) database from January 2010 to December 2017. The predictors of mortality were determined in multivariate analysis including age, sex, insurance, annual income, region of the country, mechanism of injury, mental health conditions (schizophrenia; depression; and anxiety, bipolar, and personality disorders), chronic illnesses (hypertension, diabetes, obesity, and dementia), and social risk factors such as alcohol addiction, smoking, and substance abuse. RESULTS: From 2010 to 2017, there were 979,383 ED visits for attempted suicides in the NEDS database. Among these patients, 10,301 (1.1%) died. Of these completed suicides, 73.9% were male with the median age of 43 years (IQR, 30) while the unsuccessful suicide attempt group had a median age of 30 years (IQR, 24) and were 42.7% male. The most common mechanisms of suicide attempt were poisoning (58.8%) and cut injury (25.6%). Gunshot was the most lethal mechanism accounting 40.3% of the completed suicides despite representing 1.3% of the attempts who came to ED. After controlling for common risk factors for attempted suicide, significant predictors of completed suicide include higher income status, uninsured status, male sex, and higher age. DISCUSSION: Among US patients presenting to the ED following attempted suicide, factors associated with suicide completion include increasing age, male sex, higher income, gunshot injuries, and uninsured status.

Evaluating Outcomes of Spinopelvic Fixation for Patients Undergoing Long Segment Thoracolumbar Fusion with a Prior Total Hip Arthroplasty.

INTRODUCTION: Understanding the relationship between spinal fusion and its effects on relative spinopelvic alignment in patients with prior total hip arthroplasty (THA) is critical. However, limited data exist on the effects of long spinal fusions on hip alignment in patients with a prior THA. Our objective was to compare clinical outcomes and changes in hip alignment between patients undergoing long fusion to the sacrum versus to the pelvis in the setting of prior THA. METHODS: Patients with a prior THA who underwent elective thoracolumbar spinal fusion starting at L2 or above were retrospectively identified. Patients were placed into one of two groups: fusion to the sacrum or pelvis. Preoperative, six-month postoperative, one-year postoperative, and delta spinopelvic and acetabular measurements were measured from standing lumbar radiographs. RESULTS: A total of 112 patients (55 sacral fusions, 57 pelvic fusions) were included. Patients who underwent fusion to the pelvis experienced longer length of stay (LOS) (8.31 vs. 4.21, P < 0.001) and less frequent home discharges (30.8% vs. 61.9%, P = 0.010), but fewer spinal revisions (12.3% vs. 30.9%, P = 0.030). No difference was observed in hip dislocation rates (3.51% vs. 1.82%, P = 1.000) or hip revisions (5.26% vs. 3.64%, P = 1.000) based on fusion construct. Fusion to the sacrum alone was an independent predictor of an increased spine revision rate (odds ratio: 3.56, P = 0.023). Patients in the pelvic fusion group had lower baseline lumbar lordosis (LL) (29.2 vs. 42.9, P < 0.001), six-month postoperative LL (38.7 vs. 47.3, P = 0.038), and greater 1-year ∆ pelvic incidence-lumbar lordosis (-7.98 vs. 0.21, P = 0.032). CONCLUSION: Patients with prior THA undergoing long fusion to the pelvis experienced longer LOS, more surgical complications, and lower rate of spinal revisions. Patients with instrumentation to the pelvis had lower LL preoperatively with greater changes in LL and pelvic incidence-lumbar lordosis postoperatively. No differences were observed in acetabular positioning, hip dislocations, or THA revision rates between groups.

Evaluating the Effect of Gastroesophageal Reflux Disease on Postoperative Dysphagia Following Anterior Cervical Spine Surgery-A Prospective, Multicenter Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: The purpose of this study was to prospectively evaluate the impact of a preoperative diagnosis of gastroesophageal reflux disease on the incidence and severity of postoperative dysphagia in a multicenter population. METHODS: After Institutional Review Board approval, written informed consent was obtained from all participating patients. Patients over 18 years of age who underwent an elective anterior cervical discectomy and fusion for a degenerative condition were prospectively enrolled at two academic centers from the years 2018 to 2020. Patients were separated into two groups: those with and without a preoperative diagnosis of GERD. Continuous variables were assessed using either an independent t-test or Mann Whitney U-test for parametric and non-parametric data. All categorical variables were compared using a chi-square test. RESULTS: A total of 116 patients met study criteria and were subsequently enrolled. Overall rates of postoperative dysphagia increased to 47.3% (n = 53) at 2-weeks but eventually decreased towards the preoperative prevalence of 25.0% at the 24-week mark. Patients with preoperative diagnosis of GERD had lower dysphagia severity scores on a continuous variable analysis in both the DSQ and EAT-10 surveys at 2-week follow-up in addition to the Bazaz survey at 24-week follow-up. Our follow up at 24-weeks was 85.7%. CONCLUSIONS: Our study shows that having a preoperative diagnosis of GERD has no significant effect on the incidence of dysphagia following ACDF. Nevertheless, having a preoperative diagnosis of GERD does seem to provide some protective effect on the severity of dysphagia that this patient population develops at multiple intervals over a 24-week postoperative period.

Short-Segment versus Long-Segment Spinal Fusion Constructs for the Treatment of Adult Degenerative Scoliosis: A Comparison of Clinical Outcomes.

OBJECTIVE: To compare clinical outcomes of patients diagnosed with degenerative scoliosis undergoing short-segment versus long-segment spinal fusion. METHODS: A retrospective cohort study was conducted of patients with degenerative thoracolumbar scoliosis undergoing elective spinal fusion at a single academic medical center. Cohorts were divided into short-segment (<3) or long-segment (≥3) groups. RESULTS: A total of 197 patients (122 short, 75 long) were included. Patients undergoing short-segment fusion more frequently presented with radiculopathy (P < 0.001) and had greater baseline visual analog scale (VAS) leg scores (P < 0.001). Patients with long-segment fusions had longer hospital length of stay (short, 3.82 ± 2.98 vs. long, 7.40 ± 6.85 days; P < 0.001), lower home discharge rates (short, 80.3% vs. long, 51.8; P = 0.003), higher revision surgery rates (short, 10.77% vs. long, 25.3%; P = 0.012), and greater percentage curve correction (short, 37.3% ± 25.9% vs. long, 45.1% ± 23.9%; P = 0.048). No significant differences were noted in postoperative complication rates (short, 1.64% vs. long, 5.33%; P = 0.143). At 1 year, patients with long fusions had worse ΔOswestry Disability Index (ODI) (P = 0.024), ΔVAS leg score (P = 0.002), and VAS leg minimum clinically important difference % (P = 0.003). Multivariate regression found that short-segment fusions were associated with greater improvements in ODI (P = 0.029), Physical Component Summary-12 (P = 0.024), and VAS leg score at 1 year (P = 0.002). CONCLUSIONS: Patients undergoing short-segment fusions more frequently presented with radiculopathy and had higher preoperative VAS leg scores compared with those receiving long constructs. Short-construct fusions in appropriately selected patients may provide satisfactory improvements in patient-reported outcome measures, particularly ΔODI and ΔVAS leg score, and mitigate hospital length of stay, revision surgery rates, and nonhome discharge.

Salmonellosis Outbreak Detected by Automated Spatiotemporal Analysis - New York City, May-June 2019.

In May 2019, the New York City Department of Health and Mental Hygiene (NYCDOHMH) detected an unusual cluster of five salmonellosis patients via automated spatiotemporal analysis of notifiable diseases using free SaTScan software (1). Within 1 day of cluster detection, graduate student interviewers determined that three of the patients had eaten prepared food from the same grocery store (establishment A) located inside the cluster area. NYCDOHMH initiated an investigation to identify additional cases, establish the cause, and provide control recommendations. Overall, 15 New York City (NYC) residents with laboratory-diagnosed salmonellosis who reported eating food from establishment A were identified. The most commonly consumed food item was chicken, reported by 10 patients. All 11 clinical isolates available were serotyped as Salmonella Blockley, sequenced, and analyzed by core genome multilocus sequence typing; isolates had a median difference of zero alleles. Environmental assessments revealed food not held at the proper temperature, food not cooled properly, and potential cross-contamination during chicken preparation. Elevated fecal coliform counts were found in two of four ready-to-eat food samples collected from establishment A, and Bacillus cereus was detected in three. The outbreak strain of Salmonella was isolated from one patient's leftover chicken. Establishing automated spatiotemporal cluster detection analyses for salmonellosis and other reportable diseases could aid in the detection of geographically focused, community-acquired outbreaks even before laboratory subtyping results become available.

The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning.

Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation. Loss of IDOL in neurons results in constitutive overexpression of ApoER2 and is associated with impaired activity-dependent structural remodeling of spines and defective LTP in primary neuron cultures and hippocampal slices. IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning. These results identify control of lipoprotein receptor abundance by IDOL as a post-transcriptional mechanism underlying the structural and functional plasticity of synapses and neural circuits.

Supporting cross-cultural online discussion with formal and informal platforms: a case between Hong Kong and Taiwan.

The paper reports on a collaborative project on fostering cross-cultural online discussion between two universities with one in Hong Kong and the other in Taiwan. Two online platforms-Moodle as a formal channel for course-related discussion and Facebook as an informal channel for social-oriented interaction-were employed. The study pays special attention to instructional design based on research-derived strategies and reflects on the effects of various strategies as well as students' experiences and perceptions. The results show that the students perceived the online discussion as valuable for exchanging perspectives and enhancing cross-cultural understanding. However, they were less motivated to use Facebook as the informal channel for socialization. The challenges encountered especially those concerning using Facebook in formal learning environments will be discussed. At the end, the recommendations for better utilizing and bringing together formal and informal online platforms will be suggested.

Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity.

PURPOSE: To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and in elderly patients with untreated AML and heart disease. PATIENTS AND METHODS: Patients with relapsed/refractory AML and older patients for whom there was a concern over toxicity from additional anthracyclines received 5 days of clofarabine, 40 mg/m(2) per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m(2) per day i.v. over 2 hours. RESULTS: Thirty patients were enrolled. The median age was 67 years (range, 38-82 years) and 18 (60%) had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for anthracycline toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, including a CR in 14 patients (47%). Responses were observed in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median disease-free survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation. CONCLUSIONS: Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML.

The relation of Internet use to prosocial and antisocial behavior in Chinese adolescents.

Prosocial and antisocial Internet use is investigated in this study by constructing an objective measure called the Adolescent Internet Use Questionnaire (AIUQ). The sample consists of 509 secondary school students in Hong Kong. Based on the previous review of the literature, the present study tests the following two hypotheses: (a) sex difference hypothesis: boys are more delinquent in Internet use than are girls; (b) positive association hypothesis: there is a positive association between Internet behavior and daily social behavior. In other words, positive Internet behavior is positively associated with positive daily social behavior, and negative Internet behavior is positively associated with negative daily social behavior. In general, the two hypotheses are supported by the data in this study. The internal consistency reliability and predictive validity of the major indices of the AIUQ are also substantiated by the present data.

Transcriptional and posttranscriptional inhibition of lysyl oxidase expression by cigarette smoke condensate in cultured rat fetal lung fibroblasts.

Lysyl oxidase (LO) catalyzes crosslinking of collagen and elastin essential for maintaining the structural integrity of the lung extracellular matrix (ECM). To understand mechanisms of cigarette smoke (CS)-induced emphysema, we investigated effects of cigarette smoke condensate (CSC), the particulate matter of CS, on LO mRNA expression in cultured rat fetal lung fibroblasts (RFL6). Exposure of RFL6 cells to 0-120 microg CSC/ml for 24 h induced a dose-dependent inhibition of LO steady-state mRNAs, for example, reducing transcript levels to below 10% of the control in cells incubated with 80-120 microg CSC/ml. Nuclear run-on assays indicated a marked reduction in LO relative transcriptional rates amounting to 27.7% of the control in cells treated with 120 microg CSC/ml. The actinomycin D-chase assay showed that CSC enhanced the instability of LO transcripts. The t1/2 for LO mRNA decay was decreased from 24 h in the control to 4.5 h in cells treated with 120 microg CSC/ml. Moreover, 80-120 microg CSC/ml also inhibited LO promoter activity as revealed by suppression of reporter gene expression in cells transfected with LO promoter-luciferase vectors. Thus, inhibition of LO transcription initiation and enhancement of LO mRNA instability both contributed to downregulation of LO steady-state mRNA in CSC-treated cells. Note that inhibition of LO mRNA expression by CSC was closely accompanied by markedly decreased levels of transcripts of collagen type I and tropoelastin, two substrates of LO. Thus, transcriptional perturbation of LO and its substrates may be a critical mechanism for ECM damage in CS-induced emphysema.

Lysyl oxidase oxidizes basic fibroblast growth factor and inactivates its mitogenic potential.

Lysyl oxidase (LO) plays a central role in the crosslinking of collagen and elastin in the extracellular matrix. Here we demonstrate that basic fibroblast growth factor (bFGF), a polypeptide which regulates proliferation, differentiation, and migration of a variety of cell types, is a substrate of LO. The oxidation of lysine residues in bFGF by LO resulted in the covalent crosslinking of bFGF monomers to form dimers and higher order oligomers and dramatically altered its biological properties. Both the mitogenic potential and the nuclear localization of bFGF were markedly inhibited in the Swiss 3T3 cells upon its oxidation by LO. NIH 3T3 IgBNM 6-1 cells (6-1 cells) overexpress bFGF which participates in an autocrine mechanism accounting for the transformation of these cells into a tumorigenic state. Exposure of the 6-1 cells to nanomolar concentrations of LO in culture oxidized lysine and generated crosslinkages in bFGF within the cell and markedly reduced proliferative rates. The lack of LO expression has been correlated with hyperproliferative cell growth, while this enzyme has been identified as a suppressor of ras-induced tumorigenesis. The present results illustrate a mechanism by which LO can depress normal and transformed cell growth.