1.Estimation of risk posed by malignant polyps amongst colorectal surgeons in Australia and New Zealand
Andrew P. ZAMMIT ; Ian BROWN ; John D. HOOPER ; David A. CLARK ; Andrew D. RIDDELL
Annals of Coloproctology 2024;40(2):114-120
Purpose:
The estimation of the risk posed by malignant polyps for residual or lymphatic disease plays a central role. This study investigated colorectal surgeons’ assessment of these risks associated with malignant polyps.
Methods:
A cross-sectional questionnaire was electronically administered to colorectal surgeons in Australia and New Zealand in October 2022. The questionnaire contained 17 questions on demographics, when surgeons consider colorectal resection appropriate, and the risk assessment for 5 hypothetical malignant polyps.
Results:
The mean risk of residual or lymphatic disease that would prompt surgeons to recommend colonic resection was 5%. However, this increased to a mean risk of 10% if the malignant polyp was located in the rectum, and the only resection option was abdominoperineal resection with end-colostomy. There was high concordance between the estimated risk of residual or lymphatic disease by colorectal surgeons and the Association of Coloproctology of Great Britain and Ireland (ACPGBI) guidelines for the 5 hypothetical malignant polyps, with the ACPGBI estimated risk lying within the 95% confidence interval for 4 of the 5 malignant polyps. Nonetheless, 96.6% of surgeons felt that an online risk calculator would improve clinical practice.
Conclusion
Colorectal surgeons in Australia and New Zealand accurately estimated the risk posed by malignant polyps. An online risk calculator may assist in better conveying risk to patients.
2.Are critical size bone notch defects possible in the rabbit mandible?
Patricia L CARLISLE ; Teja GUDA ; David T SILLIMAN ; Robert G HALE ; Pamela R BROWN BAER
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2019;45(2):97-107
OBJECTIVES: Small animal maxillofacial models, such as non-segmental critical size defects (CSDs) in the rabbit mandible, need to be standardized for use as preclinical models of bone regeneration to mimic clinical conditions such as maxillofacial trauma. The objective of this study is the establishment of a mechanically competent CSD model in the rabbit mandible to allow standardized evaluation of bone regeneration therapies. MATERIALS AND METHODS: Three sizes of bony defect were generated in the mandibular body of rabbit hemi-mandibles: 12 mm×5 mm, 12 mm×8 mm, and 15 mm×10 mm. The hemi-mandibles were tested to failure in 3-point flexure. The 12 mm×5 mm defect was then chosen for the defect size created in the mandibles of 26 rabbits with or without cautery of the defect margins and bone regeneration was assessed after 6 and 12 weeks. Regenerated bone density and volume were evaluated using radiography, micro-computed tomography, and histology. RESULTS: Flexural strength of the 12 mm×5 mm defect was similar to its contralateral; whereas the 12 mm×8 mm and 15 mm×10 mm groups carried significantly less load than their respective contralaterals (P<0.05). This demonstrated that the 12 mm×5 mm defect did not significantly compromise mandibular mechanical integrity. Significantly less (P<0.05) bone was regenerated at 6 weeks in cauterized defect margins compared to controls without cautery. After 12 weeks, the bone volume of the group with cautery increased to that of the control without cautery after 6 weeks. CONCLUSION: An empty defect size of 12 mm×5 mm in the rabbit mandibular model maintains sufficient mechanical stability to not require additional stabilization. However, this defect size allows for bone regeneration across the defect. Cautery of the defect only delays regeneration by 6 weeks suggesting that the performance of bone graft materials in mandibular defects of this size should be considered with caution.
Animals
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Bone Density
;
Bone Regeneration
;
Cautery
;
Mandible
;
Rabbits
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Radiography
;
Regeneration
;
Transplants
3.Are critical size bone notch defects possible in the rabbit mandible?
Patricia L CARLISLE ; Teja GUDA ; David T SILLIMAN ; Robert G HALE ; Pamela R BROWN BAER
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2019;45(2):97-107
OBJECTIVES:
Small animal maxillofacial models, such as non-segmental critical size defects (CSDs) in the rabbit mandible, need to be standardized for use as preclinical models of bone regeneration to mimic clinical conditions such as maxillofacial trauma. The objective of this study is the establishment of a mechanically competent CSD model in the rabbit mandible to allow standardized evaluation of bone regeneration therapies.
MATERIALS AND METHODS:
Three sizes of bony defect were generated in the mandibular body of rabbit hemi-mandibles: 12 mm×5 mm, 12 mm×8 mm, and 15 mm×10 mm. The hemi-mandibles were tested to failure in 3-point flexure. The 12 mm×5 mm defect was then chosen for the defect size created in the mandibles of 26 rabbits with or without cautery of the defect margins and bone regeneration was assessed after 6 and 12 weeks. Regenerated bone density and volume were evaluated using radiography, micro-computed tomography, and histology.
RESULTS:
Flexural strength of the 12 mm×5 mm defect was similar to its contralateral; whereas the 12 mm×8 mm and 15 mm×10 mm groups carried significantly less load than their respective contralaterals (P<0.05). This demonstrated that the 12 mm×5 mm defect did not significantly compromise mandibular mechanical integrity. Significantly less (P<0.05) bone was regenerated at 6 weeks in cauterized defect margins compared to controls without cautery. After 12 weeks, the bone volume of the group with cautery increased to that of the control without cautery after 6 weeks.
CONCLUSION
An empty defect size of 12 mm×5 mm in the rabbit mandibular model maintains sufficient mechanical stability to not require additional stabilization. However, this defect size allows for bone regeneration across the defect. Cautery of the defect only delays regeneration by 6 weeks suggesting that the performance of bone graft materials in mandibular defects of this size should be considered with caution.
4.Arylamine-acetyltransferase 2 genotype-dependent-acetylation of isoniazid in cryopreserved human hepatocytes.
Mark A DOLL ; Raúl A SALAZAR-GONZÁLEZ ; Srineil BODDULURI ; David W HEIN
Acta Pharmaceutica Sinica B 2017;7(4):517-522
Cryopreserved human hepatocytes were used to investigate the role of arylamine-acetyltransferase 2 (NAT2; EC 2.3.1.5) polymorphism on the-acetylation of isoniazid (INH).genotype was determined by Taqman allelic discrimination assay and INH-acetylation was measured by high performance liquid chromatography. INH-acetylation ratesexhibited a robust and highly significant (<0.005) NAT2 phenotype-dependent metabolism.-acetylation rateswere INH concentration- and time-dependent. Following incubation for 24 h with 12.5 or 100 µmol/L INH, acetyl-INH concentrations varied significantly (= 0.0023 and= 0.0002) across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. The clear association betweengenotype and phenotype supports use ofgenotype to guide INH dosing strategies in the treatment and prevention of tuberculosis.
5.Multislice CT Angiography of Fenestrated Endovascular Stent Grafting for Treating Abdominal Aortic Aneurysms: a Pictorial Review of the 2D/3D Visualizations.
Zhonghua SUN ; Bibombe P MWIPATAYI ; Yvonne B ALLEN ; David E HARTLEY ; Michael M LAWRENCE-BROWN
Korean Journal of Radiology 2009;10(3):285-293
Fenestrated endovascular repair of an abdominal aortic aneurysm has been developed to treat patients with a short or complicated aneurysm neck. Fenestration involves creating an opening in the graft fabric to accommodate the orifice of the vessel that is targeted for preservation. Fixation of the fenestration to the renal arteries and the other visceral arteries can be done by implanting bare or covered stents across the graft-artery ostia interfaces so that a portion of the stent protrudes into the aortic lumen. Accurate alignment of the targeted vessels in a longitudinal aspect is hard to achieve during stent deployment because rotation of the stent graft may take place during delivery from the sheath. Understanding the 3D relationship of the aortic branches and the fenestrated vessel stents following fenestration will aid endovascular specialists to evaluate how the stent graft is situated within the aorta after placement of fenestrations. The aim of this article is to provide the 2D and 3D imaging appearances of the fenestrated endovascular grafts that were implanted in a group of patients with abdominal aortic aneurysms, based on the multislice CT angiography. The potential applications of each visualization technique were explored and compared with the 2D axial images.
Aged
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Aged, 80 and over
;
Aorta, Abdominal/radiography
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Aortic Aneurysm, Abdominal/*radiography/*surgery
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*Blood Vessel Prosthesis
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Contrast Media/administration & dosage
;
Female
;
Humans
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Image Processing, Computer-Assisted/methods
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Imaging, Three-Dimensional/*methods
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Iohexol/administration & dosage/analogs & derivatives
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Male
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Middle Aged
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Prosthesis Design
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Radiographic Image Enhancement/methods
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*Stents
;
Tomography, X-Ray Computed/*methods
6.Investigation of a pre-clinical mandibular bone notch defect model in miniature pigs: clinical computed tomography, micro-computed tomography, and histological evaluation.
Patricia L. CARLISLE ; Teja GUDA ; David T. SILLIMAN ; Wen LIEN ; Robert G. HALE ; Pamela R. BROWN BAER
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2016;42(1):20-30
OBJECTIVES: To validate a critical-size mandibular bone defect model in miniature pigs. MATERIALS AND METHODS: Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks. RESULTS: In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. CONCLUSION: The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.
Autografts
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Bone Regeneration
;
Bone Remodeling
;
Dental Implants
;
Hand
;
Mandible
;
Swine*
7.A survey on the dioxin level in breast milk in coastal and inland region.
Yi-he JIN ; Hui-chi CHEN ; Hui-jun TANG ; Xiu-hua JIN ; Hui-fang LIU ; Zhen LI ; F KAYAMA ; A HUMAMATSU ; K SAGISAKA ; David BROWN ; George CLARK ; M NAKAMURA
Chinese Journal of Preventive Medicine 2003;37(6):439-441
OBJECTIVETo study the dioxin level of breast milk among Chinese mothers, and to assess the dioxin intake of new-born babies from mother's milk and compare with the Tolerable Daily Intake (TDI) of dioxin.
METHODSThe CALUX bioassay was used to detect the dioxin concentration of the first time mother's milk among the inland samples (Shenyang region; 32 cases) and the coastal city samples (Dalian region; 47 cases).
RESULTSThe median value of the dioxin Toxic Equivalence (TEQ) in breast milk in the Dalian region was 15.84 pg TEQs.g(-1) fat, which was significantly higher than that in the Shenyang region 7.21 pg TEQs.g(-1) fat (P < 0.01).
CONCLUSIONThe dioxin level in breast milk in Chinese is at the world's average level. The dioxin intake of the new-born babies during the period of lactation was higher than the lowest limit of the Tolerable Daily Intake (TDI) proposed by WHO. This situation should be noticed by the related authorities.
China ; Dioxins ; analysis ; Female ; Humans ; Milk, Human ; metabolism
8.TGF-β induces Smad2 Phosphorylation, ARE Induction, and Trophoblast Differentiation
Renee E ALBERS ; Kaisa SELESNIEMI ; David R C NATALE ; Thomas L BROWN
International Journal of Stem Cells 2018;11(1):111-120
BACKGROUND: Transforming growth factor beta (TGF-β) signaling has been shown to control a large number of critical cellular actions such as cell death, differentiation, and development and has been implicated as a major regulator of placental function. SM10 cells are a mouse placental progenitor cell line, which has been previously shown to differentiate into nutrient transporting, labyrinthine-like cells upon treatment with TGF-β. However, the signal transduction pathway activated by TGF-β to induce SM10 progenitor differentiation has yet to be fully investigated. MATERIALS AND METHODS: In this study the SM10 labyrinthine progenitor cell line was used to investigate TGF-β induced differentiation. Activation of the TGF-β pathway and the ability of TGF-β to induce differentiation were investigated by light microscopy, luciferase assays, and Western blot analysis. RESULTS AND CONCLUSIONS: In this report, we show that three isoforms of TGF-β have the ability to terminally differentiate SM10 cells, whereas other predominant members of the TGF-β superfamily, Nodal and Activin A, do not. Additionally, we have determined that TGF-β induced Smad2 phosphorylation can be mediated via the ALK-5 receptor with subsequent transactivation of the Activin response element. Our studies identify an important regulatory signaling pathway in SM10 progenitor cells that is involved in labyrinthine trophoblast differentiation.
Activins
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Animals
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Blotting, Western
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Cell Death
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Luciferases
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Mice
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Microscopy
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Phosphorylation
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Placenta
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Protein Isoforms
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Response Elements
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Signal Transduction
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Stem Cells
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Transcriptional Activation
;
Transforming Growth Factor beta
;
Trophoblasts
9.Contrasting clinical characteristics and treatment patterns in women with newly diagnosed advanced-stage epithelial ovarian cancer in Australia, South Korea and Taiwan
Hung-Hsueh CHOU ; Sian FEREDAY ; Anna DEFAZIO ; Chih-Long CHANG ; David BOWTELL ; Heng-Cheng HSU ; Nadia TRAFICANTE ; Soo Young JEONG ; Wen-Fang CHENG ; Dinuka ARIYARANTNE ; ; Teresa TUNG ; Viraj RAJADHYAKSHA ; Won-Hee LEE ; David BROWN ; Byoung-Gie KIM
Journal of Gynecologic Oncology 2023;34(1):e3-
Objective:
The real-world INFORM study analyzed sociodemographics, treatment patterns and clinical outcomes for patients with newly diagnosed advanced epithelial ovarian cancer (EOC) in Australia, South Korea (S.Korea) and Taiwan preceding incorporation of poly(ADP-ribose) polymerase inhibitors into clinical practice.
Methods:
Retrospective data from patients diagnosed with EOC (high-grade serous EOC for Taiwan) between January 2014 and December 2018 with ≥12 months follow-up from diagnosis were analyzed descriptively. Survival was evaluated by Kaplan-Meier with two-sided 95% confidence interval (CI).
Results:
Of the 987 patients (Australia, 223; S.Korea, 513; Taiwan, 251), 98% received platinum-based chemotherapy (CT). In S.Korea and Taiwan 76.0% and 78.9% respectively underwent primary cytoreductive surgery; in Australia, 56.5% had interval debulking surgery. Bevacizumab was included in primary/maintenance therapy for 22.4%, 14.6% and 6.8% of patients in Australia, S.Korea and Taiwan, respectively. Patients receiving bevacizumab were high-risk (reimbursement policy) and achieved similar real-world progression-free survival (PFS) compared with CT only. Overall, the median real-world PFS (months; 95% CI) was similar across Australia (16.0 [14.63–18.08]), S.Korea (17.7 [16.18–19.27]) and Taiwan (19.1 [17.56–22.29]).
Conclusion
This study reveals poor prognosis despite differences in demographics and treatment patterns for patients with EOC across Asia-Pacific suggesting the need for biomarker-driven novel therapies to improve outcomes.
10.Silent Intracerebral Hemorrhage in Patients Randomized to Stenting or Endarterectomy for Symptomatic Carotid Stenosis
Mandy D MÜLLER ; Lisa M JONGEN ; Aysun ALTINBAS ; Kristine A BLACKHAM ; Paul J NEDERKOORN ; Sumaira MACDONALD ; Rolf JÄGER ; Thomas WOLFF ; Philippe A LYRER ; L Jaap KAPPELLE ; Stephan G WETZEL ; Toby RICHARDS ; Jeroen HENDRIKSE ; Gert J DE BORST ; H Bart VAN DER WORP ; Stefan T ENGELTER ; David J WERRING ; Martin M BROWN ; Leo H BONATI
Journal of Stroke 2019;21(1):116-119
No abstract available.
Carotid Stenosis
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Cerebral Hemorrhage
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Endarterectomy
;
Humans
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Stents