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1.
Neuroradiol J ; 35(1): 86-93, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34224285

RESUMO

INTRODUCTION: Dural venous sinus stenting (VSS) is an effective, durable treatment for patients with idiopathic intracranial hypertension (IIH) due to underlying venous sinus stenosis. However, the use of venous sinus stenting to treat IIH with acute vision loss has rarely been described. METHODS: A retrospective chart analysis identified patients who received VSS for fulminant IIH, defined as acute (< 8 weeks) visual field loss to within the central 5° and/or a decrease in visual acuity to less than or equal to 20/50 in either eye in the presence of papilledema. RESULTS: Ten patients were identified with average patient age of 31.0 years, and all except one were female. Mean body mass index was 41.2 kg/m2. All patients presented with vision loss and some with headache and tinnitus. The average trans-stenotic gradient pre-stenting was 28.7 mmHg (range 9-62 mmHg). All patients had diminished or resolved venous gradients immediately following the procedure. At mean follow-up of 60.5 weeks, 100% had improvements in papilledema, 80.0% had subjective vision improvement, 55.6% had headache improvement and 87.5% had tinnitus improvement. 90.0% had stable or improved visual acuity in both eyes with a mean post-stenting Snellen acuity of 20/30 and an average gain of 3 lines Snellen acuity post-stenting (95% confidence intervals 0.1185-0.4286, p = 0.0018). Two patients (20.0%) required further surgical treatment (cerebrospinal shunting and/or stenting) after their first stenting procedure. CONCLUSIONS: This series suggests that VSS is feasible in patients presenting with IIH and acute vision loss with a fairly low complication rate and satisfactory clinical outcomes.


Assuntos
Hipertensão Intracraniana , Papiledema , Pseudotumor Cerebral , Adulto , Cavidades Cranianas/diagnóstico por imagem , Cavidades Cranianas/cirurgia , Feminino , Humanos , Pseudotumor Cerebral/complicações , Pseudotumor Cerebral/diagnóstico por imagem , Pseudotumor Cerebral/cirurgia , Estudos Retrospectivos , Stents
2.
J Clin Neurosci ; 95: 88-93, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34929657

RESUMO

Optimal management of metastatic lung cancer to the spine (MLCS) incorporates a multidisciplinary approach. With improvements in lung cancer screening andnonsurgical treatment, the role for surgerymay be affected. The objective of this study is to assess trends in the surgical management of MLCS using the National Inpatient Sample (NIS) database. The NIS was queried for patients with MLCS who underwent surgery from 2005 to 2014. The frequencies of spinal decompression alone, spinal stabilization with or without (+/-) decompression, and vertebral augmentation were calculated. Statistical analysis was performed to analyze the effect of patient characteristics on outcomes. The most common procedure performed was vertebral augmentation (10719, 44.3%), followed by spinal stabilization +/- decompression (8634, 35.7%) and then decompression alone (4824, 20.0%). The total number of surgeries remained stable, while the rate of spinal stabilizations increased throughout the study period (p < 0.001). Invasive procedures such as stabilization and decompression were associated with greater costs, length of stay,complications and mortality. Increasingcomorbidity was associated with increased odds of complication, especially in patients undergoing more invasive procedures. In patients with lowpre-operative comorbidity, the type of procedure did not influence the odds of complication. Graded increases in length of stay, cost and mortality were seen with increasing complication rate.The rate of spinal stabilizations increased, which may be due to either increased early detection of disease facilitating use of outpatient vertebral augmentation procedures and/or the recognition that surgical decompression and stabilization are necessary for optimal outcome in the setting of MLCS with neurological deficit.


Assuntos
Neoplasias Pulmonares , Fusão Vertebral , Descompressão Cirúrgica , Detecção Precoce de Câncer , Humanos , Pacientes Internados , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos
3.
J Clin Neurosci ; 91: 99-104, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34373068

RESUMO

Management of metastatic breast cancer to the spine (MBCS) incorporates a multimodal approach. Improvement in screening and nonsurgical therapies may alter the trends in surgical management of MBCS. The objective of this study is to assess trends in surgical management of MBCS and short-term outcomes based on the National Inpatient Sample (NIS) database. The NIS database was queried for patients with MBCS who underwent surgery from 2005 to 2014. The weighted frequencies of spinal decompression alone, spinal stabilization +/- decompression, and vertebral augmentation were calculated. Multivariate analysis was performed to analyze the effect of patient characteristics on outcomes stratified by procedure. The most common procedure performed was vertebral augmentation (11,114, 53.4%), followed by stabilization +/- decompression (6,906, 33.2%) and then decompression alone (3,312, 13.4%). The total population-adjusted rate of surgical management for MBCS remained stable, while the rate of spinal stabilization increased (P < 0.001) and vertebral augmentation decreased (p < 0.003). The risk of complication increased with spinal stabilization and decompression compared to vertebral augmentation procedures in those with fewer comorbidities. This relative increase in risk abated in patients with higher numbers of pre-operative comorbidities. Any single complication was associated with increases in length of stay, cost, and mortality. The rate of in-hospital interventions remained stable over the study period. Stratified by procedure, the rate of stabilizations increased with a concomitant decrease in vertebral augmentations, which suggests that patients who require hospitalization for MBCS are becoming more likely to represent advanced cases that are not amenable to palliative vertebral augmentation procedures.


Assuntos
Neoplasias da Mama , Doenças da Coluna Vertebral/cirurgia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Descompressão Cirúrgica , Feminino , Hospitalização , Humanos , Incidência , Pacientes Internados , Complicações Pós-Operatórias , Estudos Retrospectivos , Doenças da Coluna Vertebral/etiologia , Fusão Vertebral
4.
Surg Neurol Int ; 12: 48, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33654551

RESUMO

BACKGROUND: The postoperative length of stay (LOS) is an important prognostic indicator for patients undergoing instrumented spinal fusion surgery. Increased LOS can be associated with higher infection rates, higher incidence of venous thromboembolisms, and a greater frequency of hospital-acquired delirium. The day of surgery and early postoperative mobilization following single-level posterior thoracolumbar stabilizations may impact the LOS. In this study, we evaluated the effects of weekday (Monday-Thursday) versus weekend (Friday-Sunday) surgery and postoperative rehabilitation services on LOS following primarily transforaminal lumbar interbody fusion (TLIF) for degenerative spondylolisthesis (DS). METHODS: In this single-institution retrospective chart review, we identified 198 adults who received a one-level thoracolumbar instrumented fusion through a posterior only approach (2017-2019). The majority of these patients underwent TLIF for DS. A zero truncated negative binomial model was used for predictors of the primary outcome of LOS (weekday of surgery, duration of operation, first or repeat surgery, and physical therapy/ occupational therapy [PT/OT] evaluation). Covariates were sex, age, and body mass index. RESULTS: We found that operative duration, repeat surgery, and in-hospital PT/OT all significantly increased the LOS (P < 0.05). Furthermore, those undergoing weekday surgery (Monday-Thursday) had 1.29 times longer LOS than those on the weekend (Friday-Sunday), but this did not reach statistical significance (P = 0.09). CONCLUSION: In our patient sample, duration, repeat surgery, and in-hospital PT/OT increased the LOS following primarily TLIF for DS. The increased LOS in these cases is likely due to higher overall disease burden and case complexity. In addition, those patients with a greater likelihood of extended recovery and ongoing neurologic deficits are more likely to have PT/OT evaluations. Notably, LOS was not significantly impacted by the day of surgery at our institution.

5.
Cerebrovasc Dis ; 50(2): 231-238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33556951

RESUMO

Cerebral arteriovenous malformations (AVMs) are leading causes of lesional hemorrhagic stroke in both the pediatric and young adult population, with sporadic AVMs accounting for the majority of cases. Recent evidence has identified somatic mosaicism in key proximal components of the RAS-MAPK signaling cascade within endothelial cells collected from human sporadic cerebral AVMs, with early preclinical models supporting a potential causal role for these mutations in the pathogenesis of these malformations. Germline mutations that predispose to deregulation of the RAS-MAPK signaling axis have also been identified in hereditary vascular malformation syndromes, highlighting the key role of this signaling axis in global AVM development. Herein, we review the most recent genomic and preclinical evidence implicating somatic mosaicism in the RAS-MAPK signaling pathway in the pathogenesis of sporadic cerebral AVMs. Also, we review evidence for RAS-MAPK dysregulation in hereditary vascular malformation syndromes and present a hypothesis suggesting that this pathway is central for the development of both sporadic and syndrome-associated AVMs. Finally, we examine the clinical implications of these recent discoveries and highlight potential therapeutic targets within this signaling pathway.


Assuntos
Genes ras , Malformações Arteriovenosas Intracranianas/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Mosaicismo , Mutação , Transdução de Sinais/genética , Regulação da Expressão Gênica no Desenvolvimento , Predisposição Genética para Doença , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/enzimologia , Malformações Arteriovenosas Intracranianas/terapia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fenótipo , Prognóstico , Fatores de Risco
6.
J Neurointerv Surg ; 13(5): 465-470, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32732257

RESUMO

BACKGROUND: Dural venous sinus stenting (VSS) is an effective treatment for idiopathic intracranial hypertension (IIH) in adult patients. There are no published series to date evaluating safety and efficacy of VSS in pediatric patients. OBJECTIVE: To report on procedural device selection and technique as well as safety and efficacy of VSS for pediatric patients with medically refractory IIH due to underlying venous sinus stenosis. METHODS: A multi-institutional retrospective case series identified patients with medically refractory IIH aged less than 18 years who underwent VSS. RESULTS: 14 patients were identified at four participating centers. Patient ages ranged from 10 to 17 years, and 10 patients (71.4%) were female. Mean body mass index was 25.7 kg/m2 (range 15.8-34.6 kg/m2). Stenting was performed under general endotracheal anesthesia in all except two patients. The average trans-stenotic gradient during diagnostic venography was 10.6 mm Hg. Patients had stents placed in the superior sagittal sinus, transverse sinus, sigmoid sinus, occipital sinus, and a combination. Average follow-up was 1.7 years after stenting. Six patients out of 10 (60%) had reduced medication dosing, 12 of 14 patients (85.7%) had improvements in headaches, two patients (100%) with pre-stent tinnitus had resolution of symptoms, and four (80%) of five patients with papilledema had improvement on follow-up ophthalmological examinations. Two patients (14.3%) developed postprocedural groin hematomas, one patient (7.1%) developed a groin pseudoaneurysm, and one patient (7.1%) had postprocedural groin bleeding. No other procedural complications occurred. Four patients (28.6%) required further surgical treatment (cerebrospinal shunting and/or stenting) after their first stenting procedure. CONCLUSIONS: This series suggests that VSS is feasible in a pediatric population with IIH and has a low complication rate and good clinical outcomes.


Assuntos
Cavidades Cranianas/diagnóstico por imagem , Cavidades Cranianas/cirurgia , Procedimentos Neurocirúrgicos/métodos , Pseudotumor Cerebral/diagnóstico por imagem , Pseudotumor Cerebral/cirurgia , Stents , Adolescente , Criança , Feminino , Seguimentos , Humanos , Masculino , Procedimentos Neurocirúrgicos/tendências , Estudos Retrospectivos , Stents/tendências , Resultado do Tratamento
7.
Cureus ; 12(6): e8687, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32699686

RESUMO

Background The oblique lumbar interbody fusion or anterior-to-psoas (OLIF/ATP) technique relies on a corridor anterior to the psoas and posterior to the vasculature for lumbar interbody fusion. This is evaluated preoperatively with CT and/or MRI. To date, there have been no studies examining how intraoperative, lateral decubitus positioning may change the dimensions of this corridor when compared to preoperative imaging. Objective Our objective was to evaluate changes in the intraoperative corridor in the supine and lateral positions utilizing preoperative and intraoperative imaging. Methods We performed a retrospective analysis among patients who have undergone an OLIF/ATP approach at two tertiary care centers from 2016 to 2018 by measuring the distance between the left lateral border of the aorta or iliac vessels and anteromedial border of the psoas muscle from L1-L2 through L4-5 disc spaces. We compared this corridor between supine, preoperative MRI axial and intraoperative CT acquired in the right lateral decubitus position. Results Thirty-three patients, 15 of whom were female, were included in our study. The average age of the patients was 65.4 years and the average BMI was 31 kg/m2. The results revealed a statistically significant increase (p<.05) in the intraoperative corridor from supine to lateral decubitus positioning at all levels. However, age, BMI, and gender had no statistically significant impact on the preoperative versus intraoperative corridor. Conclusion This is the first study to provide objective evidence that lateral decubitus positioning increases the intraoperative corridor for OLIF/ATP. Our study demonstrates that lateral decubitus positioning provides a more favorable corridor for the OLIF/ATP technique from L1-L5 disc levels.

8.
World Neurosurg ; 136: 234-247, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31899393

RESUMO

Edward Archibald, Professor of Surgery at McGill University (1904-1945), Montreal, Canada, was the foremost thoracic surgeon of his generation. Although instrumental in establishing the American Board of Surgery and in standardizing surgical training, he was also influential as a neurosurgeon. Archibald, an early member invited by Harvey Cushing to join the Society of Neurological Surgeons, helped establish neurosurgery as a distinct, specialized discipline. We review Archibald's contributions to the development of neurosurgery in light of his encyclopedic 1908 monograph, "Surgical Affections and Wounds of the Head," which we compare and contrast to the contemporary treatise by Cushing in the same year. Through his writings and correspondence with Wilder Penfield and Cushing, we also describe his role in the creation of the Montreal Neurological Institute. Primary archival sources addressing the professional relationship between Archibald and Cushing and between Archibald and Penfield were consulted. Archibald's personal acquaintance with the principal neurosurgeons of the day, his insight into their personalities, their prominence in the field, and their career paths played a critical role in influencing Penfield to consider relocating to Montreal from Columbia University, despite tempting offers from Boston and Philadelphia. However, it was Archibald's support and mentorship for the creation of an academic center that finally convinced Penfield to move to McGill University. As one of the most influential surgeons of the early 20th century and a founding figure of modern neurosurgery, Archibald is an important part of neurosurgery's legacy.


Assuntos
Neurocirurgia/história , Canadá , História do Século XIX , História do Século XX , Humanos , Cirurgiões/história
9.
World Neurosurg ; 86: 419-31, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26463398

RESUMO

OBJECTIVE: The three-dimensional (3D) endoscope is a novel tool that provides stereoscopic vision and may allow for improved dexterity and safety during surgical resection of ventral skull base lesions. We describe here the cumulative experience available in the neurosurgical literature. METHODS: A PubMed literature review was performed to identify and analyze all studies pertaining to 3D endoscopic endonasal skull base surgery. RESULTS: We identified 26 articles: 14 clinical articles, 5 simulated environment studies, 5 human cadaveric studies, and 2 expert opinions. In all the clinical studies, 262 patients were treated for the following 257 pathologies listed in the articles: 190 suprasellar/parasellar lesions (73.9%), 41 ventral skull base lesions (16.0%), 19 sinonasal pathologies (7.4%), and 7 cerebrospinal fluid leak repairs (2.7%). Complication rates, operative time, length of hospital stay, and extent of tumor resection were equivalent between two-dimensional (2D) and 3D endoscopy. However, all studies reported that subjective depth perception and spatial orientation were markedly improved with 3D technology. In 3 studies (11.5%), it was concluded that there was no clinically significant surgical benefit in switching from 2D to 3D endoscopy. All cadaveric studies and expert opinions concluded that 3D endoscopy improved the identification of key anatomical structures and was superior to 2D endoscopy. Simulated environment studies demonstrated that 3D endoscopy improved speed and accuracy of endonasal tasks, more so in novice surgeons. CONCLUSIONS: Our findings suggest that 3D endoscopy provides improved surgical dexterity by affording the surgeon with depth perception when manipulating tissue and maneuvering the endoscope in the endonasal corridor.


Assuntos
Endoscopia , Imageamento Tridimensional , Base do Crânio/patologia , Base do Crânio/cirurgia , Humanos , Resultado do Tratamento
10.
J Clin Neurosci ; 22(11): 1708-13, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26206758

RESUMO

We aimed to determine the clinical indications and surgical outcomes for thoracoscopic discectomy. Thoracic disc disease is a rare degenerative process. Thoracoscopic approaches serve to minimize tissue injury during the approach, but critics argue that this comes at the cost of surgical efficacy. Current reports in the literature are limited to small institutional patient series. We systematically identified all English language articles on thoracoscopic discectomy with at least two patients, published from 1994 to 2013 on MEDLINE, Science Direct, and Google Scholar. We analyzed 12 articles that met the inclusion criteria, five prospective and seven retrospective studies comprising 545 surgical patients. The overall complication rate was 24% (n=129), with reported complications ranging from intercostal neuralgia (6.1%), atelectasis (2.8%), and pleural effusion (2.6%), to more severe complications such as pneumonia (0.8%), pneumothorax (1.3%), and venous thrombosis (0.2%). The average reported postoperative follow-up was 20.5 months. Complete resolution of symptoms was reported in 79% of patients, improvement with residual symptoms in 10.2%, no change in 9.6%, and worsening in 1.2%. The minimally invasive endoscopic approaches to the thoracic spine among selected patients demonstrate excellent clinical efficacy and acceptable complication rates, comparable to the open approaches. Disc herniations confined to a single level, with small or no calcifications, are ideal for such an approach, whereas patients with calcified discs adherent to the dura would benefit from an open approach.


Assuntos
Discotomia/métodos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Torácicas/cirurgia , Toracoscopia/métodos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
11.
Surg Neurol Int ; 5: 60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24872922

RESUMO

BACKGROUND: The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed. METHODS: A COMPREHENSIVE LITERATURE SEARCH WAS PERFORMED UTILIZING PUBMED AND KEY WORDS: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics. RESULTS: Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications. CONCLUSION: In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery.

12.
Neurosurg Focus ; 36(2): E8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24484261

RESUMO

Glioblastoma is the most common primary brain tumor with a median 12- to 15-month patient survival. Improving patient survival involves better understanding the biological mechanisms of glioblastoma tumorigenesis and seeking targeted molecular therapies. Central to furthering these advances is the collection and storage of surgical biopsies (biobanking) for research. This paper addresses an imaging modality, confocal reflectance microscopy (CRM), for safely screening glioblastoma biopsy samples prior to biobanking to increase the quality of tissue provided for research and clinical trials. These data indicate that CRM can immediately identify cellularity of tissue biopsies from animal models of glioblastoma. When screening fresh human biopsy samples, CRM can differentiate a cellular glioblastoma biopsy from a necrotic biopsy without altering DNA, RNA, or protein expression of sampled tissue. These data illustrate CRM's potential for rapidly and safely screening clinical biopsy samples prior to biobanking, which demonstrates its potential as an effective screening technique that can improve the quality of tissue biobanked for patients with glioblastoma.


Assuntos
Bancos de Espécimes Biológicos , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Animais , Bancos de Espécimes Biológicos/normas , Biópsia , Linhagem Celular Tumoral , Humanos , Microscopia Confocal/métodos , Ratos , Ratos Nus , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
13.
Neurosurg Focus ; 36(2): E9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24484262

RESUMO

Laser scanning confocal endomicroscopy (LSCE) is an emerging technology for examining brain neoplasms in vivo. While great advances have been made in macroscopic fluorescence in recent years, the ability to perform confocal microscopy in vivo expands the potential of fluorescent tumor labeling, can improve intraoperative tissue diagnosis, and provides real-time guidance for tumor resection intraoperatively. In this review, the authors highlight the technical aspects of confocal endomicroscopy and fluorophores relevant to the neurosurgeon, provide a comprehensive summary of LSCE in animal and human neurosurgical studies to date, and discuss the future directions and potential for LSCE in neurosurgery.


Assuntos
Neoplasias Encefálicas/cirurgia , Procedimentos Neurocirúrgicos/tendências , Salas Cirúrgicas/tendências , Animais , Neoplasias Encefálicas/diagnóstico , Previsões , Humanos , Microscopia Confocal/tendências
14.
J Pregnancy ; 2012: 812094, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23133755

RESUMO

Constant maternal hyperglycemia limits, while pulsatile maternal hyperglycemia may enhance, fetal glucose-stimulated insulin secretion (GSIS) in sheep. However, the impact of such different patterns of hyperglycemia on the development of the fetal ß-cell is unknown. We measured the impact of one week of chronic constant hyperglycemia (CHG, n = 6) versus pulsatile hyperglycemia (PHG, n = 5) versus controls (n = 7) on the percentage of the fetal pancreas staining for insulin (ß-cell area), mitotic and apoptotic indices and size of fetal ß-cells, and fetal insulin secretion in sheep. Baseline insulin concentrations were higher in CHG fetuses (P < 0.05) compared to controls and PHG. GSIS was lower in the CHG group (P < 0.005) compared to controls and PHG. PHG ß-cell area was increased 50% (P < 0.05) compared to controls and CHG. CHG ß-cell apoptosis was increased over 400% (P < 0.05) compared to controls and PHG. These results indicate that late gestation constant maternal hyperglycemia leads to significant ß-cell toxicity (increased apoptosis and decreased GSIS). Furthermore, pulsatile maternal hyperglycemia increases pancreatic ß-cell area but did not increase GSIS, indicating decreased ß-cell responsiveness. These findings demonstrate differential effects that the pattern of maternal hyperglycemia has on fetal pancreatic ß-cell development, which might contribute to later life limitation in insulin secretion.


Assuntos
Desenvolvimento Fetal/fisiologia , Hiperglicemia/fisiopatologia , Células Secretoras de Insulina/patologia , Complicações na Gravidez/fisiopatologia , Animais , Apoptose , Doença Crônica , Feminino , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperplasia/etiologia , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Masculino , Mitose , Pâncreas/citologia , Pâncreas/embriologia , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Distribuição Aleatória , Ovinos
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