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1.
Am Surg ; : 31348241259033, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38867656

ABSTRACT

BACKGROUND: Multimodal pain management has been shown to be effective in treating pain in acutely injured trauma patients. Our community-based, level 1 trauma center previously published in 2022 the efficacy of implementing multimodal pain control (MMPC) protocol in our inpatient trauma population which decreased the use of opioids while maintaining similar pain control. The MMPC group had a trend toward higher age and was significantly less injured. We hypothesize MMPC will reduce opioid consumption in both the advanced aged and more severely injured trauma populations while still providing adequate pain control. METHODS: Defined by the year of admission, MMPC and physician managed pain control (PMPC) were compared in both advanced age groups and between the severely injured groups. The advanced age group included patients ≥55 years old. The severely injured group included ≥18 years old with ≥15 ISS. Primary outcomes were total opioid utilization per day, calculated in morphine milliequivalents (MME), and median daily pain scores. RESULTS: For the severely injured population, the MMPC group showed a 3-fold decrease in opioid use (30 MME/d vs 90.3 MME/d, P < .001) and lower pain scores (5/10 vs 6/10, P < .001) than the PMPC group. In the advance age group, there was no significant difference between MMPC and PMPC groups in opioid use (P = .974) or pain scores (P = .553). CONCLUSION: MMPC effectively reduces opioid consumption in a severely injured patient population while simultaneously improving pain control. Advanced age trauma patients can require complex pain management solutions and future research to determine their needs is recommended.

2.
Am Surg ; : 31348241241712, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38591174

ABSTRACT

BACKGROUND: Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe. METHODS: This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test. RESULTS: 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P < .05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849 923 annually and $3 399 693 over the study period. DISCUSSION: Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39 million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient.

5.
Am Surg ; 89(7): 3148-3152, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36880710

ABSTRACT

Whole blood (WB) for trauma resuscitation in civilian populations has become more common. The utilization of WB in community trauma centers has not been reported. Previous studies have centered around large academic medical centers. We hypothesized that WB-based resuscitation compared to component-only resuscitation (CORe) would demonstrate a survival benefit and that WB resuscitation is safe, feasible, and benefits trauma patients regardless of setting. Our results indicate that receiving whole blood during resuscitation conferred a clear survival benefit to discharge, and this benefit was independent of ISS, age, gender, and initial SBP. We conclude WB should be incorporated into all resuscitation protocols for exsanguinating trauma patients and preferred over component therapy in all centers treating trauma patients.


Subject(s)
Blood Transfusion , Wounds and Injuries , Humans , Blood Transfusion/methods , Trauma Centers , Resuscitation/methods , Exsanguination , Patient Discharge , Wounds and Injuries/therapy , Wounds and Injuries/etiology
6.
Am Surg ; 89(8): 3444-3448, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36920989

ABSTRACT

INTRODUCTION: Small bowel obstruction is a common surgical complaint. Most small bowel obstructions are managed successfully nonoperatively. Unanimous guidelines for nonoperative management of small bowel obstruction do not exist. METHODS: A standardized protocol for water-soluble contrast administration and abbreviated small bowel follow through imaging was implemented in January of 2021. A retrospective chart review identified 111 patients admitted for SBO from 6/2019 to 9/2019 for a control group. A planned follow-up review identified 158 patients managed according to the new protocol from 3/2021 to 10/2021. The primary outcome was in-hospital length of stay. Standard statistical analyses were performed and pre-specified. RESULTS: Before implementation of the standardized protocol patients that were managed strictly nonoperatively, the mean length of stay (LOS) was 8.3 days. After implementation, the average LOS was 4.8 (P < .0001). Comparatively, patients admitted after protocol implementation were more likely to undergo CT scan with PO contrast on admission (98.1% vs 90.1%; P < .005), undergo NG tube decompression (84.7% vs 68.5%; P < .005), and undergo water-soluble contrast with abbreviated or formal SBFT (75.3% vs 37.8%; P < .0001). CONCLUSION: Implementation of a standardized protocol utilizing abbreviated SBFT with water-soluble contrast for the management of SBO at our institution resulted in a decrease in the average length of stay for patients definitively managed in a nonoperative fashion.


Subject(s)
Intestinal Obstruction , Humans , Retrospective Studies , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Contrast Media , Tomography, X-Ray Computed , Length of Stay , Water , Treatment Outcome
7.
Am Surg ; 89(7): 3278-3280, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36853882

ABSTRACT

Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality worldwide. Severe TBI carries the greatest risk of brain death progression. There are currently no laboratory markers that predict patient's outcome. We hypothesize that the degree of hypophosphatemia (HP) in TBI is an indicator for progression to brain death. A total of 336 patients, ages 15-89, with a GCS of 8 or less at admission were identified and retrospectively analyzed. Demographics, laboratory studies, and brain death (BD) were collected. Univariate analysis demonstrated HP was correlated with BD (P < .0002). Multivariate analysis showed that phosphate was the only measured electrolyte correlated to BD with a P value < .0001. Mechanism of hypophosphatemia may be related to BD progression and provide future areas for study.


Subject(s)
Brain Injuries, Traumatic , Hypophosphatemia , Humans , Brain Death , Retrospective Studies , Brain Injuries, Traumatic/complications , Hospitalization , Hypophosphatemia/etiology , Glasgow Coma Scale
8.
Am J Case Rep ; 23: e936628, 2022 Nov 16.
Article in English | MEDLINE | ID: mdl-36442847

ABSTRACT

BACKGROUND Persistent left superior vena cava (PLSVC) results in a double superior vena cava (SVC), and although it is rare, this is the most common venous anomaly of the thorax. PSLVC arises from the junction of the left subclavian and internal jugular veins. It is identified on the left side of the mediastinum adjacent to the aortic arch, and it usually drains into the right atrium through the coronary sinus. This report presents the case of a 40-year-old man with an incidental finding of double SVC due to PSLVC identified on hospital admission following a motor vehicle collision. CASE REPORT A 40-year-old man was found to have a double SVC due to PLSVC upon chest radiography during hospital admission for injuries related to motor vehicle trauma. The discovery was made following placement of a central venous catheter (CVC) down the left-sided SVC and into the coronary sinus. The patient suffered no harm as a result. The diagnosis was made by chest radiography and confirmed by computed tomography angiography. CONCLUSIONS PSLVC is an uncommon condition that can complicate common procedures and therefore must be well-understood by physicians across many medical and surgical specialties. Although PLSVC may be asymptomatic, as in this case, in some patients PLSVC presents as atrial fibrillation or with nonspecific cardiac symptoms. Therefore, all patients identified with PLSVC should be investigated to exclude associated cardiac abnormalities and arrythmias, and before the placement of central venous access devices.


Subject(s)
Catheterization, Central Venous , Central Venous Catheters , Persistent Left Superior Vena Cava , Male , Humans , Adult , Vena Cava, Superior/diagnostic imaging , Catheterization, Central Venous/adverse effects , Thorax , Central Venous Catheters/adverse effects
9.
Pediatr Crit Care Med ; 23(1): e45-e54, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34261942

ABSTRACT

OBJECTIVES: To derive and internally validate a bronchiolitis-specific illness severity score (the Critical Bronchiolitis Score) that out-performs mortality-based illness severity scores (e.g., Pediatric Risk of Mortality) in measuring expected duration of respiratory support and PICU length of stay for critically ill children with bronchiolitis. DESIGN: Retrospective database study using the Virtual Pediatric Systems (VPS, LLC; Los Angeles, CA) database. SETTING: One-hundred twenty-eight North-American PICUs. PATIENTS: Fourteen-thousand four-hundred seven children less than 2 years old admitted to a contributing PICU with primary diagnosis of bronchiolitis and use of ICU-level respiratory support (defined as high-flow nasal cannula, noninvasive ventilation, invasive mechanical ventilation, or negative pressure ventilation) at 12 hours after PICU admission. INTERVENTIONS: Patient-level variables available at 12 hours from PICU admission, duration of ICU-level respiratory support, and PICU length of stay data were extracted for analysis. After randomly dividing the cohort into derivation and validation groups, patient-level variables that were significantly associated with the study outcomes were selected in a stepwise backward fashion for inclusion in the final score. Score performance in the validation cohort was assessed using root mean squared error and mean absolute error, and performance was compared with that of existing PICU illness severity scores. MEASUREMENTS AND MAIN RESULTS: Twelve commonly available patient-level variables were included in the Critical Bronchiolitis Score. Outcomes calculated with the score were similar to actual outcomes in the validation cohort. The Critical Bronchiolitis Score demonstrated a statistically significantly stronger association with duration of ICU-level respiratory support and PICU length of stay than mortality-based scores as measured by root mean squared error and mean absolute error. CONCLUSIONS: The Critical Bronchiolitis Score performed better than PICU mortality-based scores in measuring expected duration of ICU-level respiratory support and ICU length of stay. This score may have utility to enrich interventional trials and adjust for illness severity in observational studies in this very common PICU condition.


Subject(s)
Bronchiolitis , Intensive Care Units, Pediatric , Bronchiolitis/diagnosis , Bronchiolitis/therapy , Child , Child, Preschool , Humans , Infant , Length of Stay , Respiration, Artificial , Retrospective Studies
10.
Am Surg ; 88(3): 376-379, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34892995

ABSTRACT

INTRODUCTION: The Brain Trauma Foundation advises intracranial pressure monitor placement (ICPM) following traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) score ≤8 and an abnormal head computed tomographic scan (CT) finding. Prior studies demonstrated that ICPMs could be placed by non-neurosurgeons. We hypothesized that ICPM placement by trauma critical care surgeons (TCCS) would increase appropriate utilization (AU), decrease time to placement (TTP), and have equivalent complications to those placed by neurosurgeons. METHODS: We retrospectively reviewed medical records of adult trauma patients admitted with a TBI in a historical control group (HCG) and practice change group (PCG). Demographics, Injury Severity Score (ISS), outcomes, ICPM placement by provider type, and time to placement were identified. Complications and appropriate utilization were recorded. RESULTS: 70 patients in the HCG and 84 patients in the PCG met criteria for inclusion. Demographics, arrival GCS, ICU GCS, ISS, and admission APACHE II scores were not statistically significant. AU was 7/70 for HCG vs 19/84 in the PCG (P = .04036). Median TTP was 6.5 hours for HCG vs 5.25 for PCG (P = .9308). Interquartile range showed the data clustered around an earlier placement time, 2.3-14.0 hours, in the PCG. Complications between the 2 groups were not statistically significant, 0/7 for HCG vs 5/19 for PCG (P = .2782). DISCUSSION: This study confirms that ICPMs can be safely placed by TCCS. Our results demonstrate that placement of ICPMs by TCCS improves AU and possibly improves TTP.


Subject(s)
Brain Injuries, Traumatic , Intracranial Pressure , Monitoring, Physiologic/instrumentation , Prosthesis Implantation , Surgeons , Traumatology , APACHE , Adult , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/diagnostic imaging , Female , Glasgow Coma Scale , Historically Controlled Study , Humans , Injury Severity Score , Male , Middle Aged , Neurosurgeons , Prosthesis Implantation/adverse effects , Retrospective Studies , Safety , Time-to-Treatment , Tomography, X-Ray Computed , Treatment Outcome
11.
Blood Coagul Fibrinolysis ; 32(1): 37-43, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33196508

ABSTRACT

To determine if there is a significant association between administration of tranexamic acid (TXA) in severely bleeding, injured patients, and venous thromboembolism (VTE), myocardial infarction (MI), or cerebrovascular accident (CVA). A multicenter, retrospective study was performed. Inclusion criteria were: age 18-80 years old and need for 5 units or more of blood in the first 24 h after injury. Exclusion criteria included: death within 24 h, pregnancy, administration of TXA more than 3 h following injury, and routine ultrasound surveillance for deep venous thrombosis. Incidence of VTE was the primary outcome. Secondary outcomes included MI, CVA, and death. A power analysis found that a total of 830 patients were needed to detect a true difference in VTE risk. 1333 patients (TXA = 887, No-TXA = 446 patients) from 17 centers were enrolled. There were no differences in age, shock index, Glasgow coma score, pelvis/extremity abbreviated injury score, or paralysis. Injury severity score was higher in the No-TXA group. Incidence of VTE, MI, or CVA was similar between the groups. The TXA group required significantly less transfusion (P < 0.001 for all products) and had a lower mortality [adjusted odds ratio 0.67 (95% confidence interval 0.45-0.98)]. Despite having a higher extremity/pelvis abbreviated injury score, results did not change when evaluating only patients with blunt injury. Use of TXA in bleeding, injured patients is not associated with VTE, MI, or CVA but is associated with a lower transfusion need and mortality.


Subject(s)
Venous Thromboembolism/epidemiology , Wounds and Injuries/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Tranexamic Acid , Young Adult
14.
Trauma Surg Acute Care Open ; 4(1): e000351, 2019.
Article in English | MEDLINE | ID: mdl-31799416

ABSTRACT

INTRODUCTION: Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. METHODS: We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. RESULTS: 825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. CONCLUSION: We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. LEVEL OF EVIDENCE: Level II.

15.
Am Surg ; 81(5): 454-7, 2015 May.
Article in English | MEDLINE | ID: mdl-25975327

ABSTRACT

Sentinel lymph node biopsy (SLNB) is used to detect axillary lymph node metastases in breast cancer. Preoperative radiocolloid injection with lymphoscintigraphy (PL) is performed before SLNB. Few comparisons between 1- and 2-day PL protocols exist. Opponents of a 2-day protocol have expressed concerns of radiotracer washout to nonsentinel nodes. Proponents cite lack of scheduling conflicts between PL and surgery. A total of 387 consecutive patients with clinically node-negative breast cancer underwent SLNB with PL. Lymphoscintigraphy images were obtained within 30 minutes of radiocolloid injection. Axillary lymph node dissection was performed if the sentinel lymph node (SLN) could not be identified. Data were collected regarding PL technique and results. In all, 212 patients were included in the 2-day PL group and 175 patients in the 1-day PL group. Lymphoscintigraphy identified an axillary sentinel node in 143/212 (67.5%) of patients in the 2-day group and 127/175 (72.5%) in the 1-day group (P = 0.28). SLN was identified at surgery in 209/212 (98.6%) patients in the 2-day group and 174/175 (99.4%) in the 1-day group (P = 0.41). An average of 3 SLN was found at surgery in the 2-day group compared with 3.15 in the 1-day group (P = 0.43). SLN was positive for metastatic disease in 54/212 (25.5%) patients in the 2-day group compared with 40/175 (22.9%) in the 1-day group (P = 0.55). A 2-day lymphoscintigraphy protocol allows reliable detection of the SLN, of positive SLN and equivalent SLN harvest compared with a 1-day protocol. The timing of radiocolloid injection before SLNB can be left at the discretion of the surgeon.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Lymphoscintigraphy , Preoperative Care/methods , Sentinel Lymph Node Biopsy , Axilla , Female , Humans , Lymphatic Metastasis , Middle Aged , Retrospective Studies , Time Factors
16.
J Appl Psychol ; 99(6): 1222-43, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25133304

ABSTRACT

Although one of the most well-established research findings in industrial-organizational psychology is that general mental ability (GMA) is a strong and generalizable predictor of job performance, this meta-analytically derived conclusion is based largely on measures of task or overall performance. The primary purpose of this study is to address a void in the research literature by conducting a meta-analysis to determine the direction and magnitude of the correlation of GMA with 2 dimensions of nontask performance: counterproductive work behaviors (CWB) and organizational citizenship behaviors (OCB). Overall, the results show that the true-score correlation between GMA and CWB is essentially 0 (-.02, k = 35), although rating source of CWB moderates this relationship. The true-score correlation between GMA and OCB is positive but modest in magnitude (.23, k = 43). The 2nd purpose of this study is to conduct meta-analytic relative weight analyses to determine the relative importance of GMA and the five-factor model (FFM) of personality traits in predicting nontask and task performance criteria. Results indicate that, collectively, the FFM traits are substantially more important for CWB than GMA, that the FFM traits are roughly equal in importance to GMA for OCB, and that GMA is substantially more important for task and overall job performance than the FFM traits. Implications of these findings for the development of optimal selection systems and the development of comprehensive theories of job performance are discussed along with study limitation and future research directions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).


Subject(s)
Employee Performance Appraisal , Intelligence , Personality , Work/psychology , Humans , Organizational Culture , Social Behavior
17.
J Appl Psychol ; 98(4): 623-41, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23731029

ABSTRACT

Despite the wide use of physical ability tests for selection and placement decisions in physically demanding occupations, research has suggested that there are substantial male-female differences on the scores of such tests, contributing to adverse impact. In this study, we present updated, revised meta-analytic estimates of sex differences in physical abilities and test 3 moderators of these differences-selection system design, specificity of measurement, and training-in order to provide insight into possible methods of reducing sex differences on physical ability test scores. Findings revealed that males score substantially better on muscular strength and cardiovascular endurance tests but that there are no meaningful sex differences on movement quality tests. These estimates differ in several ways from past estimates. Results showed that sex differences are similar across selection systems that emphasize basic ability tests versus job simulations. Results also showed that sex differences are smaller for narrow dimensions of muscular strength and that there is substantial variance in the sex differences in muscular strength across different body regions. Finally, we found that training led to greater increases in performance for women than for men on both muscular strength and cardiovascular endurance tests. However, training reduced the male-female differences on muscular strengths tests only modestly and actually increased male-female differences on cardiovascular endurance. We discuss the implications of these findings for research on physical ability testing and adverse impact, as well as the practical implications of the results.


Subject(s)
Exercise Test/statistics & numerical data , Exercise/physiology , Muscle Strength/physiology , Physical Endurance/physiology , Sex Characteristics , Female , Humans , Male , Sex Factors
18.
Malar J ; 11: 180, 2012 May 30.
Article in English | MEDLINE | ID: mdl-22646748

ABSTRACT

BACKGROUND: Human malaria infections caused by the parasite Plasmodium falciparum often contain more than one genetically distinct parasite. Despite this fact, nearly all studies of multiple strain P. falciparum infections have been limited to determining relative densities of each parasite within an infection. In light of this, new methods are needed that can quantify the absolute number of parasites within a single infection. METHODS: A quantitative PCR (qPCR) method was developed to track the dynamic interaction of P. falciparum infections containing genetically distinct parasite clones in cultured red blood cells. Allele-specific primers were used to generate a standard curve and to quantify the absolute concentration of parasite DNA within multi-clonal infections. Effects on dynamic growth relationships between parasites under drug pressure were examined by treating mixed cultures of drug sensitive and drug resistant parasites with the anti-malarial drug chloroquine at different dosing schedules. RESULTS: An absolute quantification method was developed to monitor the dynamics of P. falciparum cultures in vitro. This method allowed for the observation of competitive suppression, the reduction of parasites numbers due to the presence of another parasite, and competitive release, the improved performance of a parasite after the removal of a competitor. These studies demonstrated that the presence of two parasites led to the reduction in density of at least one parasite. The introduction of drug to a mixed culture containing both a drug resistant and drug sensitive parasites resulted in an increased proportion of the drug resistant parasite. Moreover, following drug treatment, the resistant parasite experienced competitive release by exhibiting a fitness benefit greater than simply surviving drug treatment, due to the removal of competitive suppression by the sensitive parasite. CONCLUSIONS: The newly developed assay allowed for the examination of the dynamics of two distinct clones in vitro; both competitive suppression and release were observed. A deeper understanding of the dynamic growth responses of multiple strain P. falciparum infections, with and without drug pressure, can improve the understanding of the role of parasite interactions in the spread of drug resistant parasites, perhaps suggesting different treatment strategies.


Subject(s)
Erythrocytes/parasitology , Plasmodium falciparum/classification , Plasmodium falciparum/isolation & purification , Antimalarials/pharmacology , DNA, Protozoan/genetics , Genotype , Humans , Microbial Interactions , Parasite Load , Plasmodium falciparum/genetics
19.
J Appl Psychol ; 96(4): 762-73, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21142341

ABSTRACT

Conclusions reached in previous research about the magnitude and nature of personality-performance linkages have been based almost exclusively on self-report measures of personality. The purpose of this study is to address this void in the literature by conducting a meta-analysis of the relationship between observer ratings of the five-factor model (FFM) personality traits and overall job performance. Our results show that the operational validities of FFM traits based on observer ratings are higher than those based on self-report ratings. In addition, the results show that when based on observer ratings, all FFM traits are significant predictors of overall performance. Further, observer ratings of FFM traits show meaningful incremental validity over self-reports of corresponding FFM traits in predicting overall performance, but the reverse is not true. We conclude that the validity of FFM traits in predicting overall performance is higher than previously believed, and our results underscore the importance of disentangling the validity of personality traits from the method of measurement of the traits.


Subject(s)
Personality Assessment , Personality , Databases, Bibliographic , Humans , Observer Variation , Personality Inventory , Regression Analysis , Reproducibility of Results , Self Report
20.
Endocrinology ; 147(10): 4781-91, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16809444

ABSTRACT

Intrinsic and extrinsic stimuli result in profound pituitary growth changes ranging from hypoplasia to hyperplasia. Pituitary tumor transforming gene (PTTG) abundance correlates with pituitary trophic status. Mice with Pttg inactivation exhibit pituitary hypoplasia, whereas targeted pituitary PTTG overexpression driven by alpha-subunit glycoprotein (alphaGSU) promoter results in focal pituitary hyperplasia. To test the impact of pituitary hyperplasia on tumor development, we crossbred alphaGSU.PTTG with Rb+/- mice, which develop pituitary tumors with high penetrance. Pituitary glands of resulting bitransgenic alphaGSU.PTTGxRb+/- mice were compared with monotransgenic alphaGSU.PTTG, Rb+/-, and wild-type mice. Confocal microscopy showed that PTTG-overexpressing cells have enlarged nuclei and marked redistribution of chromatin, and electron microscopy of alphaGSU.PTTG pituitaries showed enlarged gonadotrophs with prominent Golgi complexes and numerous secretory granules. These morphological findings were even more remarkable in alphaGSU.PTTGxRb+/- pituitaries. Mice from all four genotypes were sequentially imaged by magnetic resonance imaging to evaluate pituitary volume, and glands from alphaGSU.PTTGxRb+/- mice were the largest as early as 2 months of age (P = 0.0003). Cumulative incidence of pituitary tumors visualized by magnetic resonance imaging did not differ between Rb+/- and alphaGSU.PTTGxRb+/- mice. However, anterior lobe tumors determined after necropsy were 3.5 times more frequent in alphaGSU.PTTGxRb+/- than in Rb+/- mice (P = 0.0036), whereas the frequency of intermediate lobe tumors was similar. In summary, alphaGSU.PTTGxRb+/- pituitary glands exhibit enhanced cellular activity, increased volume, and higher prevalence of anterior pituitary tumors, indicating that changes in pituitary PTTG content directly relate to both pituitary trophic status and tumorigenic potential.


Subject(s)
Gene Expression Regulation, Neoplastic/genetics , Neoplasm Proteins/genetics , Pituitary Neoplasms/genetics , Animals , Chromatin/genetics , Chromatin/ultrastructure , Golgi Apparatus/metabolism , Hyperplasia/genetics , Hyperplasia/pathology , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Mice , Mice, Knockout , Microscopy, Confocal , Microscopy, Electron , Proliferating Cell Nuclear Antigen/genetics , Secretory Vesicles/metabolism , Securin
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