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1.
Neuroradiol J ; 37(1): 39-42, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37590100

ABSTRACT

PURPOSE: Imaging changes in the pituitary volume during pregnancy remains scantly researched. This study set out to assess the differences in total, anterior, and posterior pituitary volume in pregnant women compared to nulliparous and post-partum women. MATERIALS AND METHODS: A retrospective review was completed of women that had undergone MRI imaging of the brain. Patients were divided into three cohorts: pregnant, nulliparous, and post-partum (defined as being within 12 months of delivery). Anterior and posterior pituitary volumes were manually measured. RESULTS: 171 patients were included, of which 68 were pregnant, 52 were post-partum, and 51 were nulliparous. The average anterior (621.0 ± 171.6 mm3) and total (705.4 ± 172.2 mm3) pituitary volumes were significantly larger in pregnant patients than nulliparous women (522.6 ± 159.8 mm3 and 624.5 ± 163.7 mm3, respectively) (p = .002 and p = .01, respectively). The posterior pituitary volume was significantly smaller in pregnant women (84.4 ± 32.9 mm3) compared to both post-partum (101.2 ± 42.0 mm3) and nulliparous (102.0 ± 46.1 mm3) women (p = .02 for both). CONCLUSIONS: The anterior and total pituitary volumes are significantly larger during pregnancy persisting into the post-partum period. The posterior pituitary volume, conversely, decreases during pregnancy, and returns to its normal size in the post-partum period.


Subject(s)
Pituitary Diseases , Postpartum Period , Pregnancy , Female , Humans , Pituitary Gland/diagnostic imaging , Retrospective Studies , Magnetic Resonance Imaging
2.
Cancers (Basel) ; 15(18)2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37760443

ABSTRACT

Functional magnetic resonance imaging (fMRI) with blood oxygen level-dependent (BOLD) technique is useful for preoperative mapping of brain functional networks in tumor patients, providing reliable in vivo detection of eloquent cortex to help reduce the risk of postsurgical morbidity. BOLD task-based fMRI (tb-fMRI) is the most often used noninvasive method that can reliably map cortical networks, including those associated with sensorimotor, language, and visual functions. BOLD resting-state fMRI (rs-fMRI) is emerging as a promising ancillary tool for visualization of diverse functional networks. Although fMRI is a powerful tool that can be used as an adjunct for brain tumor surgery planning, it has some constraints that should be taken into consideration for proper clinical interpretation. BOLD fMRI interpretation may be limited by neurovascular uncoupling (NVU) induced by brain tumors. Cerebrovascular reactivity (CVR) mapping obtained using breath-hold methods is an effective method for evaluating NVU potential.

3.
Neurosurg Focus ; 55(2): E13, 2023 08.
Article in English | MEDLINE | ID: mdl-37527679

ABSTRACT

OBJECTIVE: The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis). METHODS: The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected. RESULTS: The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56-68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11-21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5-14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4-43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1-43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months). CONCLUSIONS: Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.


Subject(s)
Hypopituitarism , Pituitary Neoplasms , Male , Humans , Female , Aged , Retrospective Studies , Treatment Outcome , Pituitary Gland , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/surgery , Hypopituitarism/etiology , Headache
4.
Pediatrics ; 152(1)2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37340913

ABSTRACT

A full-term female was admitted at 3 days of life with a worsening rash since birth, concerning for infection. She developed clinical seizures and was transferred to our facility. She was admitted to the pediatric hospital medicine service and diagnostic workup was expanded with several specialists consulted. Presumptive diagnosis was made clinically, with definitive diagnosis established thereafter.


Subject(s)
Exanthema , Hospitalization , Infant, Newborn , Child , Humans , Female , Seizures , Exanthema/etiology , Referral and Consultation
5.
World Neurosurg ; 172: e684-e694, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36764447

ABSTRACT

OBJECTIVE: Metastasis to the pituitary gland is uncommon. With life expectancy after cancer diagnosis improving, we sought to understand the effects of treating pituitary metastasis in the modern era of advanced cancer treatment. METHODS: Patients who had been diagnosed with, and treated for, pituitary metastasis from 2000 to 2021 were retrospectively analyzed. RESULTS: A total of 48 patients were identified, of whom 23 (48%) were women. The most common primary cancer was the lung (n = 23; 48%), followed by the breast (n = 9; 19%). Of the 48 patients, 29 (60%) had had hypopituitarism and 12 (25%), visual field deficits. Twenty-seven patients (56%) had had solitary pituitary metastasis, with no evidence of other intracranial metastatic lesions. Of the 48 patients, 14 (29%) had undergone surgery and 20 (42%) had undergone standalone radiation therapy (preceded by biopsy for 3). After surgery and/or radiation therapy, the visual field deficits had improved in 6 patients, hypopituitarism had improved in 4 patients, and hypopituitarism had occurred in 3 patients. The median overall survival (OS) was 12 months (interquartile range, 3.0-28 months). Multivariate analysis showed nonsolitary pituitary metastasis (hazard ratio, 2.8; 95% confidence interval, 1.5-5.5; P = 0.0021) and no surgery or radiation therapy (hazard ratio, 2.08; 95% confidence interval, 1.04-4.15; P = 0.038) were associated with OS. For those with solitary pituitary metastasis, the patients who had undergone surgery and/or radiation therapy had had better 1-year OS than patients who had not received either (P = 0.03). In contrast, for patients with nonsolitary pituitary metastasis, those who had undergone standalone radiation therapy had had better 1-year OS than the patients who had not received either (P = 0.03). CONCLUSIONS: In the selected population, metastasis-directed therapy was associated with improved OS. Either correct patient selection for additional therapy or surgery and/or radiation therapy directly benefited patients' OS.


Subject(s)
Hypopituitarism , Pituitary Neoplasms , Humans , Female , Male , Retrospective Studies , Treatment Outcome , Pituitary Gland , Hypopituitarism/etiology , Pituitary Neoplasms/surgery , Pituitary Neoplasms/radiotherapy
6.
Interv Neuroradiol ; : 15910199221150470, 2023 Jan 17.
Article in English | MEDLINE | ID: mdl-36650942

ABSTRACT

BACKGROUND: Computed tomography (CT) angiography collateral score (CTA-CS) is an important clinical outcome predictor following mechanical thrombectomy for ischemic stroke with large vessel occlusion (LVO). The present multireader study aimed to evaluate the performance of e-CTA software for automated assistance in CTA-CS scoring. MATERIALS AND METHODS: Brain CTA images of 56 patients with anterior LVO were retrospectively processed. Twelve readers of various clinical training, including junior neuroradiologists, senior neuroradiologists, and neurologists graded collateral flow using visual CTA-CS scale in two sessions separated by a washout period. Reference standard was the consensus of three expert readers. Duration of reading time, inter-rater reliability, and statistical comparison of readers' performance metrics were analyzed between the e-CTA assisted and unassisted sessions. RESULTS: e-CTA assistance resulted in significant increase in mean accuracy (58.6% to 67.5%, p = 0.003), mean F1 score (0.574 to 0.676, p = 0.002), mean precision (58.8% to 68%, p = 0.007), and mean recall (58.7% to 69.9%, p = 0.002), especially with slight filling deficit (CTA-CS 2 and 3). Mean reading time was reduced across all readers (103.4 to 59.7 s, p = 0.001), and inter-rater agreement in CTA-CS assessment was increased (Krippendorff's alpha 0.366 to 0.676). Optimized occlusion laterality detection was also noted with mean accuracy (92.9% to 96.8%, p = 0.009). CONCLUSION: Automated assistance for CTA-CS using e-CTA software provided helpful decision support for readers in terms of improving scoring accuracy and reading efficiency for physicians with a range of experience and training backgrounds and leading to significant improvements in inter-rater agreement.

7.
Clin Neurol Neurosurg ; 224: 107562, 2023 01.
Article in English | MEDLINE | ID: mdl-36549221

ABSTRACT

OBJECTIVE: To examine an association between idiopathic transclival cerebrospinal fluid (CSF) leak and notochordal lesions. METHODS: This study consisted of the illustrations of institutional patients who underwent surgery for transclival CSF leak between January 1, 2009 and April 25, 2020 and comprehensive review of the existing literature conducted on April 25, 2020. The cases were classified based on the presumed etiologies that were originally proposed in the articles ("idiopathic" vs. "secondary"). The baseline characteristics were compared between the groups, and the surgical outcomes were summarized. RESULTS: In 3 institutional cases, ecchordosis physaliphora (EP) was confirmed at the fistula either pathologically (1) or radiologically (2). Among 42 literature cases, 28 were recognized as idiopathic, while 14 were secondary cases with histologically (n = 12) or radiologically (n = 2) confirmed notochordal lesion at the fistula. Thus, any notochordal lesions were histologically confirmed in 13 among a total of 45 cases (28.9%). Fourteen of the idiopathic cases had undescribed radiographic signs suggestive of small ecchordosis physaliphora at the fistula. Both idiopathic and secondary cases demonstrated resemblance in their ages (mean, 51.4 and 56.6 years; p = 0.102), female predominance (male, 36% vs. 25%; P = 0.521), no association with obesity (7% vs. 18%; P = 0.350) or increased intracranial pressure (7% vs. 6%; P = 1.000). All the fistulas were in the midline or paramidline clivus within several millimeters below the dorsum sellae. All the patients were treated surgically with a multilayer closure, resulting in a success rate of 93% with one surgery. CONCLUSION: Our analyses suggest the association of transclival CSF leak and notochord lesions. A prospective study is needed for definitive conclusion.


Subject(s)
Fistula , Hamartoma , Humans , Male , Female , Notochord/pathology , Cerebrospinal Fluid Leak/diagnostic imaging , Cerebrospinal Fluid Leak/etiology , Cerebrospinal Fluid Leak/surgery , Cranial Fossa, Posterior/diagnostic imaging , Cranial Fossa, Posterior/surgery , Hamartoma/complications , Fistula/diagnostic imaging , Fistula/surgery , Fistula/etiology
8.
Mayo Clin Proc ; 96(8): 2043-2057, 2021 08.
Article in English | MEDLINE | ID: mdl-34120752

ABSTRACT

OBJECTIVE: To understand the transition from microscopic surgery (MS) to endoscopic surgery (ES) on the pituitary across the United States, we assessed a single institution practicing both procedures to discern advantages and disadvantages for each. PATIENTS AND METHODS: Retrospective institutional chart review of 534 patients in a large practice over a 6-year period (January 1, 2014, to December 31, 2019) comparing a single MS neurosurgeon with a single ES neurosurgeon operating on the same days. RESULTS: In this series, 14% (n=75) of patients had a prior operation, there were no carotid artery injuries, the overall risk for a postoperative infection was 0.4% (n=2), and risk for a postoperative cerebrospinal fluid leak requiring treatment was 2.0% (n=11). Mean ± SD hospital stay was 1.3±0.04 days; readmission for any reason within 30 days occurred in 3.4% (n=18) of patients. The mean volumetric resection for MS was 86.9%±1.7% and for ES was 91.7%±1.3% (P=.03). There was a higher rate of notable events (P=.015) with MS, but MS had 16% lower cost and operative times were 48 minutes shorter than for ES (83±7 vs 131±6 minutes). The ES required substantially fewer postoperative secondary treatments such as radiation therapy (P=.003). CONCLUSION: Pituitary surgery is a very safe and effective procedure regardless of technique. The MS has shorter operative times and overall lower cost. The ES results in increased volumetric resection and fewer secondary treatments. Both techniques can be valuable to a large practice, and understanding these niches is important when selecting optimal approaches to pituitary surgery for a given patient.


Subject(s)
Endoscopy/methods , Microsurgery/methods , Pituitary Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Follow-Up Studies , Humans , Male , Middle Aged , Operative Time , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
9.
Interv Neuroradiol ; 27(6): 781-787, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33853441

ABSTRACT

INTRODUCTION: There is increased interest in the use of artificial intelligence-based (AI) software packages in the evaluation of neuroimaging studies for acute ischemic stroke. We studied whether, compared to standard image interpretation without AI, Brainomix e-ASPECTS software improved interobserver agreement and accuracy in detecting ASPECTS regions affected in anterior circulation LVO. METHODS: We included 60 consecutive patients with anterior circulation LVO who had TICI 3 revascularization within 60 minutes of their baseline CT. A total of 16 readers, including senior neuroradiologists, junior neuroradiologists and vascular neurologists participated. Readers interpreted CT scans on independent workstations and assessed final ASPECTS and evaluated whether each individual ASPECTS region was affected. Two months later, readers again evaluated the CT scans, but with assistance of e-ASPECTS software. We assessed interclass correlation coefficient for total ASPECTS and interobserver agreement with Fleiss' Kappa for each ASPECTS region with and without assistance of the e-ASPECTS. We also assessed accuracy for the readers with and without e-ASPECTS assistance. In our assessment of accuracy, ground truth was the 24 hour CT in this cohort of patients who had prompt and complete revascularization. RESULTS: Interclass correlation coefficient for total ASPECTS without e-ASPECTS assistance was 0.395, indicating fair agreement compared, to 0.574 with e-ASPECTS assistance, indicating good agreement (P < 0.01). There was significant improvement in inter-rater agreement with e-ASPECTS assistance for each individual region with the exception of M6 and caudate. The e-ASPECTS software had higher accuracy than the overall cohort of readers (with and without e-ASPECTS assistance) for every region except the caudate. CONCLUSIONS: Use of Brainomix e-ASPECTS software resulted in significant improvements in inter-rater agreement and accuracy of ASPECTS score evaluation in a large group of neuroradiologists and neurologists. e-ASPECTS software was more predictive of final infarct/ASPECTS than the overall group interpreting the CT scans with and without e-ASPECTS assistance.


Subject(s)
Brain Ischemia , Stroke , Artificial Intelligence , Brain Ischemia/diagnostic imaging , Humans , Observer Variation , Reproducibility of Results , Retrospective Studies , Software , Stroke/diagnostic imaging
10.
World Neurosurg ; 149: e197-e216, 2021 05.
Article in English | MEDLINE | ID: mdl-33610869

ABSTRACT

OBJECTIVE: To discuss optimal treatment strategy for spindle cell oncocytoma (SCO) of the pituitary gland. METHODS: Institutional cases were retrospectively reviewed. A systematic literature search and subsequent quantitative synthesis were performed for further analysis. The detailed features were summarized and the tumor control rate (TCR) was calculated. RESULTS: Eighty-five patients (6 institutional and 79 literature) were included. The annual incidence was approximately 0.01-0.03/100,000. The mean age was 56 years. Vision loss was present in 60%. Seventy-three percent showed hormonal abnormalities. On magnetic resonance imaging, tumor was avidly enhancing, and the normal gland was commonly displaced anterosuperiorly. Evidence of hypervascularity was seen in 77%. Gross total resection (GTR) was achieved in only 24% because of its hypervascular, fibrous, and adhesive nature. The mean postoperative follow-up was 3.3 years for institutional cases and 2.3 years for the integrated cohort. The TCR was significantly better after GTR (5-year TCR, 75%; P = 0.012) and marginally better after non-GTR + upfront radiotherapy (5-year TCR, 76%; P = 0.103) than after non-GTR alone (5-year TCR, 24%). The TCRs for those with low Ki-67 index (≤5%) were marginally better than those with higher Ki-67 index (5-year rate, 57% vs. 23%; P = 0.110). CONCLUSIONS: Frequent endocrine-related symptoms, hypervascular signs, and anterosuperior displacement of the gland support preoperative diagnosis of SCO. GTR seems to have better long-term tumor control, whereas the fibrous, hypervascular, and adhesive nature of SCO makes it difficult to achieve GTR. In patients with non-GTR, radiotherapy may help decrease tumor progression.


Subject(s)
Adenoma, Oxyphilic/diagnostic imaging , Adenoma, Oxyphilic/surgery , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/surgery , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies
11.
Neuroradiology ; 63(3): 439-445, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33025042

ABSTRACT

PURPOSE: We investigated the hypothesis that increasing fMRI temporal resolution using a multiband (MB) gradient echo-echo planar imaging (GRE-EPI) pulse sequence provides fMRI language maps of higher statistical quality than those acquired with a traditional GRE-EPI sequence. METHODS: This prospective study enrolled 29 consecutive patients receiving language fMRI prior to a potential brain resection for tumor, AVM, or epilepsy. A 4-min rhyming task was performed at 3.0 Tesla with a traditional GRE-EPI pulse sequence (TR = 2000, TE = 30, matrix = 64/100%, slice = 4/0, FOV = 24, slices = 30, time points = 120) and an additional MB GRE-EPI pulse sequence with an acceleration factor of 6 (TR = 333, TE = 30, matrix 64/100%, slice = 4/0, FOV = 24, time points = 720). Spatially filtered t statistical maps were generated. Volumes of interest (VOIs) were drawn around activations at Broca's, dorsolateral prefrontal cortex, Wernicke's, and the visual word form areas. The t value maxima were measured for the overall brain and each of the VOIs. A paired t test was performed for the corresponding traditional and MB GRE-EPI measurements. RESULTS: The mean age of subjects was 42.6 years old (18-75). Sixty-two percent were male. The average overall brain t statistic maxima for the MB pulse sequence (t = 15.4) was higher than for the traditional pulse sequence (t = 9.3, p = < .0001). This also held true for Broca's area (p < 0.0001), Wernicke's area (p < .0001), dorsolateral prefrontal cortex (p < .0001), and the visual word form area (p < .0001). CONCLUSION: A MB GRE-EPI fMRI pulse sequence employing high temporal resolution provides clinical fMRI language maps of greater statistical significance than those obtained with a traditional GRE-EPI sequence.


Subject(s)
Language , Magnetic Resonance Imaging , Adult , Brain Mapping , Echo-Planar Imaging , Humans , Male , Prospective Studies
12.
Magn Reson Imaging Clin N Am ; 28(4): 509-516, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33040992

ABSTRACT

MRI is a powerful diagnostic tool with excellent soft tissue contrast that uses nonionizing radiation. These advantages make MRI an appealing modality for imaging the pregnant patient; however, specific risks inherent to the magnetic resonance environment must be considered. MRI may be performed without and/or with intravenous contrast, which adds further fetal considerations. The risks of MRI with and without intravenous contrast are reviewed as they pertain to the pregnant or lactating patient and to the fetus and nursing infant. Relevant issues for gadolinium-based contrast agents and ultrasmall paramagnetic iron oxide particles are reviewed.


Subject(s)
Lactation/physiology , Magnetic Resonance Imaging/methods , Patient Safety , Pregnancy Complications/prevention & control , Prenatal Diagnosis/methods , Female , Humans , Magnetic Resonance Imaging/adverse effects , Practice Guidelines as Topic , Pregnancy
13.
Top Magn Reson Imaging ; 28(4): 213-224, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31385901

ABSTRACT

Task-based functional magnetic resonance imaging (fMRI) for the presurgical assessment of eloquent cortex is increasingly relied upon by surgeons, neurologists, and radiologists. The utility of fMRI stems from the lack of correlation between topographic anatomy and functional anatomy. fMRI can noninvasively reveal the functional anatomy of a given individual thereby allowing the surgeon to choose the most appropriate surgical trajectory, attain the most complete resection, and offer the best chance of preserving function. This dissociation between function and topography is even more critical to understand when disease distorts normal anatomic relations and when chronic evolution of pathology leads to reorganization of cortical function as can be seen with seizures or slow growing tumors. fMRI can demonstrate the functional anatomy of language, motor, vision, and memory systems. Accurate interpretation not only requires knowledge of the expected patterns of activations in the regions of interest but also demands an understanding of the many adjacent "bystander" activations that represent participatory neural activity but not the eloquent region in question. In addition, fMRI interpretation requires an understanding of the limitations of this technique when expected activity is either missing or seemingly displaced in location.


Subject(s)
Brain Diseases/diagnostic imaging , Brain Mapping/methods , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Brain/physiopathology , Brain/surgery , Brain Diseases/pathology , Brain Diseases/physiopathology , Brain Diseases/surgery , Humans , Language , Preoperative Care/methods
14.
FASEB J ; 33(2): 2409-2421, 2019 02.
Article in English | MEDLINE | ID: mdl-30303740

ABSTRACT

The dietary R-3-hydroxybutyrate- R-1,3-butanediol monoester increases resting energy expenditure (REE) and markers of brown and white adipose thermogenesis in lean mice. The purpose of this investigation was to determine whether the ketone ester, R, S-1,3-butanediol diacetoacetate (BD-AcAc2), increases energy expenditure and markers of adipose tissue thermogenesis in the context of high-fat diet (HFD)-induced obesity. Thirty-five-week-old male C57BL/6J mice were placed on an ad libitum HFD (45% kcal) for 10 wk. The mice were then randomized to 1 of 3 groups ( n = 10 per group) for an additional 12 wk: 1) control (Con), continuous HFD, 2) pair-fed (PF) to ketone ester (KE); and 3) KE: HFD+30% energy from BD-AcAc2. Mean energy intake throughout the study was ∼26% lower in the KE compared to the Con group (8.2 ± 0.5 vs. 11.2 ± 0.7 kcal/d; P < 0.05). Final body weight (26.8 ± 3.6 vs. 34.9 ± 4.8 g; P < 0.001) and fat mass (5.2 ± 1.2 vs. 11.3 ± 4.5 g; P < 0.001) of the KE group was significantly lower than PF, despite being matched for energy provisions. Differences in body weight and adiposity were accompanied by higher REE and total energy expenditure in the KE group compared to PF after adjustment for lean body mass and fat-mass ( P = 0.001 and 0.007, respectively). Coupled or uncoupled mitochondrial respiratory rates in skeletal muscle were not different among groups, but markers of mitochondrial uncoupling and thermogenesis (uncoupling protein-1, deiodinase-2, and peroxisome proliferator-activated receptor γ coactivator-1α) were higher in interscapular brown adipose tissue (BAT) of mice receiving the KE diet. The absence of mitochondrial uncoupling in skeletal muscle and increased markers of mitochondrial uncoupling in BAT suggest that BD-AcAc2 initiates a transcriptional signature consistent with BAT thermogenesis in the context of HFD-induced obesity.-Davis, R. A. H., Deemer, S. E., Bergeron, J. M., Little, J. T., Warren, J. L., Fisher, G., Smith, D. L., Jr., Fontaine, K. R., Dickinson, S. L., Allison, D. B., Plaisance, E. P. Dietary R, S-1,3-butanediol diacetoacetate reduces body weight and adiposity in obese mice fed a high-fat diet.


Subject(s)
Acetoacetates/administration & dosage , Adiposity/drug effects , Body Weight/drug effects , Butylene Glycols/administration & dosage , Diet, High-Fat/adverse effects , Energy Metabolism/drug effects , Obesity/prevention & control , Adipose Tissue, Brown/drug effects , Adipose Tissue, White/drug effects , Animals , Body Composition , Energy Intake , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/physiopathology
15.
Food Chem Toxicol ; 107(Pt A): 418-429, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28698155

ABSTRACT

Botanicals used in dietary supplements industry can have toxicology concerns related to endpoint gaps that cannot be fully resolved by a history of use, or existence of conflicting safety data. However, traditional toxicological studies on botanicals are scientifically and pragmatically challenging due to testing of complex mixtures of constituents, cost, time, and animal usage. Alternatively, we developed an in silico decision-tree approach to address data gaps and inform need for further studies by toxicologically evaluating the chemical composition of botanicals. Following advanced multi-detector analytical characterization of a botanical, each chemical constituent is: (a.) quantitatively benchmarked against similar constituents in commonly consumed foods or botanicals with well-established safety profiles, (b.) systematically evaluated for toxicity data utilizing structure-activity relationships, and, (c.) compared to established thresholds of toxicological concern in absence of safety data or structural analogs. Finally, where safety endpoint gaps are identified which cannot be resolved without additional in vitro or in vivo studies, the botanical compositional data are critical to inform on study design. Results with three herbal preparations demonstrate the utility of this novel approach to identify potential hazards and establish safe human use levels for botanicals in a cost efficient and informative manner that minimizes animal use.


Subject(s)
Chromatography, High Pressure Liquid/methods , Dietary Supplements/analysis , Drug Evaluation, Preclinical/methods , Plant Preparations/analysis , Computer Simulation , Dietary Supplements/adverse effects , Humans , Plant Preparations/adverse effects , Safety
16.
Food Chem Toxicol ; 103: 133-147, 2017 May.
Article in English | MEDLINE | ID: mdl-28267567

ABSTRACT

Despite growing popularity in dietary supplements, many medicinal mushrooms have not been evaluated for their safe human consumption using modern techniques. The multifaceted approach described here relies on five key principles to evaluate the safety of non-culinary fungi for human use: (1) identification by sequencing the nuclear ribosomal internal transcribed spacer (ITS) region (commonly referred to as ITS barcoding), (2) screening an extract of each fungal raw material against a database of known fungal metabolites, (3) comparison of these extracts to those prepared from grocery store-bought culinary mushrooms using UHPLCPDA-ELS-HRMS, (4) review of the toxicological and chemical literature for each fungus, and (5) evaluation of data establishing presence in-market. This weight-of-evidence approach was used to evaluate seven fungal raw materials and determine safe human use for each. Such an approach may provide an effective alternative to conventional toxicological animal studies (or more efficiently identifies when studies are necessary) for the safety assessment of fungal dietary ingredients.


Subject(s)
Agaricales/chemistry , Dietary Supplements/adverse effects , Toxicology/methods , Agaricales/genetics , Computer Simulation , Dietary Supplements/toxicity , Humans
17.
Food Chem ; 214: 383-392, 2017 Jan 01.
Article in English | MEDLINE | ID: mdl-27507489

ABSTRACT

One challenge in the dietary supplement industry is confirmation of species identity for processed raw materials, i.e. those modified by milling, drying, or extraction, which move through a multilevel supply chain before reaching the finished product. This is particularly difficult for samples containing fungal mycelia, where processing removes morphological characteristics, such that they do not present sufficient variation to differentiate species by traditional techniques. To address this issue, we have demonstrated the utility of DNA barcoding to verify the taxonomic identity of fungi found commonly in the food and dietary supplement industry; such data are critical for protecting consumer health, by assuring both safety and quality. By using DNA barcoding of nuclear ribosomal internal transcribed spacer (ITS) of the rRNA gene with fungal specific ITS primers, ITS barcodes were generated for 33 representative fungal samples, all of which could be used by consumers for food and/or dietary supplement purposes. In the majority of cases, we were able to sequence the ITS region from powdered mycelium samples, grocery store mushrooms, and capsules from commercial dietary supplements. After generating ITS barcodes utilizing standard procedures accepted by the Consortium for the Barcode of Life, we tested their utility by performing a BLAST search against authenticate published ITS sequences in GenBank. In some cases, we also downloaded published, homologous sequences of the ITS region of fungi inspected in this study and examined the phylogenetic relationships of barcoded fungal species in light of modern taxonomic and phylogenetic studies. We anticipate that these data will motivate discussions on DNA barcoding based species identification as applied to the verification/certification of mushroom-containing dietary supplements.


Subject(s)
Agaricales/genetics , DNA Barcoding, Taxonomic/methods , DNA, Ribosomal Spacer/genetics , Phylogeny , Sequence Analysis, DNA
18.
J Radiol Case Rep ; 10(5): 1-8, 2016 May.
Article in English | MEDLINE | ID: mdl-27761174

ABSTRACT

Extramammary Paget disease (EMPD) is an uncommon malignancy. It manifests either in the primary form in the skin as an intraepithelial neoplasm, or in secondary form as pagetoid (intraepithelial) spread of an underlying internal carcinoma to the skin. Although local invasion and recurrence of primary extramammary Paget disease are relatively frequent, widespread metastases are rare. As such, there are very few reports and little characterization of the radiologic features of widespread spinal metastases. To our knowledge, there are no prior reports of a metastatic extramammary Paget disease presenting as a painful pathologic vertebral body compression fracture. We report the radiological features of a case of primary extramammary Paget disease with subsequent spinal metastases presenting as a painful compression fracture.


Subject(s)
Fractures, Compression/diagnostic imaging , Fractures, Compression/etiology , Paget Disease, Extramammary/pathology , Skin Neoplasms/pathology , Spinal Fractures/diagnostic imaging , Spinal Fractures/etiology , Spinal Neoplasms/secondary , Biopsy , Diagnosis, Differential , Fatal Outcome , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Positron Emission Tomography Computed Tomography
19.
Radiographics ; 34(2): 472-90, 2014.
Article in English | MEDLINE | ID: mdl-24617692

ABSTRACT

Injuries to the pediatric distal forearm and wrist have myriad manifestations. Growth plate injuries can occur in the skeletally immature child. An unfused growth plate is less robust than ligamentous complexes and therefore is more easily injured. The Salter-Harris fracture classification system is used to grade physeal injuries based on their imaging appearance. This grading has prognostic significance: higher grades imply an increased likelihood of eventual growth disturbance. A disrupted distal radioulnar joint characterizes Galeazzi-type injuries at all ages; however, before skeletal maturity is attained, a disrupted radioulnar joint can manifest as a distal ulnar physeal separation with associated epiphysiolysis of the distal ulna, termed a Galeazzi-equivalent fracture. Bone contusions can be diagnosed using fluid-sensitive fat-suppressed magnetic resonance imaging, and their detection can alter the prognosis. The unique cartilaginous cushion of the developing bony carpus imparts resilience to fracture and dislocation until carpal maturity is reached. Chronic compressive forces to the wrist in a skeletally immature gymnast can result in a distinct pattern of bone and soft-tissue injury referred to as gymnast wrist. If the distal radial physis fuses prematurely, ulnar growth will outpace radial growth, leading to positive ulnar variance and consequent chronic wrist pain from ulnar impaction.


Subject(s)
Radius/diagnostic imaging , Radius/injuries , Ulna/diagnostic imaging , Ulna/injuries , Wrist Injuries/diagnostic imaging , Adolescent , Child , Female , Fractures, Bone/diagnostic imaging , Humans , Joint Dislocations/diagnostic imaging , Male , Radiography , Wrist Joint/anatomy & histology , Wrist Joint/diagnostic imaging
20.
Epilepsy Res ; 105(1-2): 216-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23352222

ABSTRACT

The prolonged seizures of status epilepticus produce chronic arrhythmogenic changes in cardiac function. This study was designed to determine if repeated, self-limiting seizures administered to kindled rats induce similar cardiac dysfunction. Multiple seizures administered to rats following hippocampal kindling resulted in cardiac QT interval prolongation and increased susceptibility to experimental arrhythmias. These data suggest that multiple, self-limiting seizures of intractable epilepsy may have cardiac effects that can contribute to sudden unexpected death in epilepsy (SUDEP).


Subject(s)
Arrhythmias, Cardiac/physiopathology , Hippocampus/physiopathology , Kindling, Neurologic/physiology , Seizures/physiopathology , Animals , Disease Susceptibility , Male , Rats , Rats, Sprague-Dawley , Time Factors
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