The World Health Organization has recognized aging as one of the most important bio-psycho-social challenges of the 21st century.
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Augmented sensory neuronal activity from the carotid body (CB) has emerged as a principal cause of hypertension in a number of cardiovascular related pathologies including obstructive sleep apnoea, heart failure and diabetes. Development of new targets and pharmacological treatment strategies aiming to reduce CB sensory activity may thus improve outcomes in these key patient cohorts. The current study tested whether ecto-5′-nucleotidase (CD73), an enzyme that generates adenosine, is functionally important in modifying CB sensory activity and cardiovascular respiratory responses to hypoxia. Inhibition of ecto-5′-nucleotidase by α,β-methylene ADP (AOPCP) in the whole CB preparation in vitro reduced basal discharge frequency by 76 ± 5% and reduced sensory activity throughout graded hypoxia. AOPCP also significantly attenuated elevations in sensory activity evoked by mitochondrial inhibition. These effects were mimicked by antagonism of adenosine receptors with 8-(p-sulfophenyl) theophylline. Infusion of AOPCP in vivo significantly decreased the hypoxic ventilatory response (Δ
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Because the lipid droplet (LD)-associated perilipin (PLIN) proteins promote intramuscular triglyceride (IMTG) storage, we investigated the hypothesis that differential protein content of PLINs and their distribution with LDs may be linked to the diverse lipid storage in muscle between trained and sedentary individuals. Trained (n = 11) and sedentary (n = 10) subjects, matched for age, sex and BMI, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0 h, 2 h, 6 h) were analysed using confocal immunofluorescence microscopy for fibre type-specific IMTG content and PLIN associations with LDs. In both groups lipid infusion increased IMTG content in type I fibres (trained: +62%, sedentary: +79%; P < 0.05), but did not affect PLIN protein content. At baseline, PLIN2 (+65%), PLIN3 (+105%) and PLIN5 (+53%; all P < 0.05) protein content was higher in trained compared to sedentary individuals. In trained individuals, lipid infusion increased the number of LDs associated with PLIN2 (+27%), PLIN3 (+73%) and PLIN5 (+40%; all P < 0.05) in type I fibres. In contrast, in sedentary individuals lipid infusion only increased the number of LDs not associated with PLIN proteins. Acute FFA elevation, therefore, induces a redistribution of PLIN proteins to an expanded LD pool in trained individuals only, and this may be part of the mechanism which enables fatty acids to be stored in IMTG.
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The role of corticospinal (CS) pathways in anticipatory motor actions was evaluated using transcranial magnetic stimulation (TMS) of the primary motor cortex projecting to motoneurons (MNs) of wrist muscles. Preloaded wrist flexors were suddenly unloaded by the experimenter or by the subject using the other hand (self-unloading). After sudden unloading, the wrist joint involuntarily flexed to a new position. In contrast, during self-unloading the wrist remained almost motionless, implying that an anticipatory postural adjustment occurred. In the self-unloading task, anticipation was manifested by a decrease in descending facilitation of pre-activated flexor MNs starting ∼72 ms before changes in the background EMG activity. Descending facilitation of extensor MNs began to increase ∼61 ms later. Conversely, these influences remained unchanged before sudden unloading, implying the absence of anticipation. We also tested TMS responses during EMG silent periods produced by brief muscle shortening, transiently resulting in similar EMG levels before the onset and after the end of self-unloading. We found reduced descending facilitation of flexor MNs after self-unloading. To explain why the wrist excursion was minimized in self-unloading due to these changes in descending influences, we relied on previous demonstrations that descending systems pre-set the threshold positions of body segments at which muscles begin to be activated, thus pre-determining the equilibrium point to which the system is attracted. Based on this notion, a more consistent explanation of the kinematic, EMG and descending patterns in the two types of unloading is proposed compared to the alternative notion of direct pre-programming of kinematic and/or EMG patterns.
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Cytologic diagnosis of extra-adrenal paraganglioma presenting as a peripancreatic mass is challenging with a high error rate due to its rarity. We report two cases of peripancreatic masses identified by radiology. Endoscopic ultrasound-guided fine needle aspiration (FNA) of the masses showed a moderately cellular tumor composed of small to medium sized neoplastic cells with round to oval nuclei, arranged singly and in loose clusters. Focal rosette-like structures were present. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin). A diagnosis of a neoplasm with neuroendocrine differentiation and neuroendocrine tumor was made respectively on FNA for each case. The subsequent surgical resection of the tumors revealed peripancreatic paraganglioma. Although paraganglioma has been reported in the literature, the detailed comparison of perpancreatic paraganglioma versus pancreatic/gastrointestinal neuroendocrine tumor is still lacking. Therefore using these two cases with literature review, we wish to illustrate the differential diagnosis between these two entities based on cytomorphology and immunohistochemical study.
Cells with long polar hair-like processes referred to as ‘flower pot cells’ are a rare but beautiful morphological feature observed in effusions of diverse etiologies. This report describes these cells in effusions seen in ovarian borderline serous tumours, malignant mesothelioma and in reactive mesothelial cells with or without accompanying malignant cells. These processes were better appreciated in air-dried May-Grunwald-Giemsa stained smears.
Publication date: Available online 30 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Man-Wook Hur, Jae-Hyeon Yoon, Min-Young Kim, Hyeonseok Ko, Bu-Nam Jeon
Kr-POK (ZBTB7c) is a kidney cancer-related POK transcription factor that not only represses transcription of CDKN1A but also increases expression of FASN. However, precisely how Kr-POK affects cell metabolism by controlling gene expression in response to an energy source in rapidly proliferating cells remains unknown. In this study, we characterized the molecular and functional features of Kr-POK in the context of tumor growth and glutamine metabolism. We found that cells expressing Kr-POK shRNA exhibited more severe cell death than control cells in glucose-deprived medium, and that knockdown of Kr-POK decreased glutamine uptake. Glutamine is critical for tumor cell proliferation. Glutaminase (GLS1), which is activated by p-STAT1, catalyzes the initial reaction in the pathway of glutaminolysis. Kr-POK interacts with PIAS1 to disrupt the interaction between PIAS1 and p-STAT1, and free p-STAT1 can activate GLS1 transcription through an interaction with p300. Kr-POK can be also sumoylated by PIAS1, facilitating Kr-POK degradation by the ubiquitin-mediated proteasomal pathway. Finally, we showed that repression of Kr-POK inhibited tumor growth in vivo in a xenograft model by repressing GLS1 expression. Taken together, our data reveal that Kr-POK activates GLS1 transcription and increases glutamine uptake to support rapid cancer cell proliferation.
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Publication date: Available online 30 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Liming Yu, Zilong Li, Mingming Fang, Yong Xu
Inflammation is considered a fundamental host defense mechanism and, when aberrantly activated, contributes to a host of human diseases. Previously we have reported that the transcriptional regulator megakaryocytic leukemia 1 (MKL1) plays a role programming cellular inflammatory response by modulating NF-κB activity. Here we report that MKL1 was acetylated in vivo and pro-inflammatory stimuli (TNF-α and LPS) augmented MKL1 acetylation accompanying increased MKL1 binding to NF-κB target promoters. Further analysis revealed that the lysine acetyltransferase PCAF mediated MKL1 acetylation: TNF-α and LPS promoted the interaction between MKL1 and PCAF while depletion of PCAF abrogated the induction of MKL1 acetylation by TNF-α and LPS. Acetylation of MKL1 was necessary for MKL1 to activate the transcription of pro-inflammatory genes because mutation of four conserved lysine residues in MKL1 attenuated its capacity as a trans-activator of NF-κB target genes. Mechanistically, MKL1 acetylation served to promote MKL1 nuclear enrichment, to enhance the MKL1-NF-κB interaction, and to stabilize the binding of MKL1 on target promoters. In conclusion, our data unveil an important pathway that contributes to the transcriptional regulation of inflammatory response.
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Purpose: Resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the cellular mechanisms mediating resistance of NSCLCs to VEGFR tyrosine kinase inhibitors.<br /><br />Experimental Design: We generated murine models of human NSCLC and performed targeted inhibition studies with the VEGFR TKIs cediranib and vandetanib. We used species-specific hybridization of microarrays to compare cancer (human) and stromal (mouse) cell transcriptomes of TKI-sensitive and -resistant tumors. We measured tumor microvascular density and vessel tortuosity to characterize the effects of therapy on the tumor vascular bed. Circulating cytokine and angiogenic factor levels in patients enrolled in VEGFR TKI trials were correlated with clinical outcomes.<br /><br />Results: Murine xenograft models of human lung adenocarcinoma were initially sensitive to VEGFR TKIs, but developed resistance to treatment. Species-specific microarray analysis identified increased expression of stromal-derived hepatocyte growth factor (HGF) as a candidate mediator of TKI resistance and its receptor, c-MET, was activated in cancer cells and tumor-associated stroma. A transient increase in hypoxia-regulated molecules in the initial response phase was followed by adaptive changes resulting in a more tortuous vasculature. Forced HGF expression in cancer cells reduced tumor sensitivity to VEGFR TKIs and produced tumors with tortuous blood vessels. Dual VEGFR/c-MET signaling inhibition delayed the onset of the resistant phenotype and prevented the vascular morphology alterations. In cancer patients receiving VEGFR TKIs, high pretreatment HGF plasma levels correlated with poorer survival. <br /><br />Conclusions: HGF/c-MET pathway mediates VEGFR inhibitor-resistance and vascular remodeling in NSCLC.
Purpose: We determined if quantifying neuroblastoma (NB)-associated mRNAs (NB-mRNA) in bone marrow (BM) and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory NB. <br /><br />Patients and Methods: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in BM and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold [Ct] for the geometric mean of genes from the TaqMan® Low Density Array NB5 assay) and morphologically-defined tumor cell percentage in BM, 123I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between DCt and progression-free survival (PFS). <br /><br />Results: NB-mRNA was detectable in 83% of BM (185/223) and 63% (89/142) of blood specimens, and their DCts were correlated (Spearman r=0.67, p<0.0001) although BM Ct was 7.9±0.5 Ct stronger than blood Ct. When BM morphology, MIBG, or CT/MRI were positive, NB-mRNA was detected in 99% (99/100), 88% (100/113), and 81% (82/101) of BMs. When all three were negative, NB-mRNA was detected in 55% (11/20) of BMs. BM NB-mRNA correlated with BM morphology or MIBG positivity (p<0.0001 and p=0.007). BM and blood Cts correlated with PFS (p<0.001; p=0.001) even when BM was morphologically negative (p=0.001; p=0.014). Multivariate analysis showed that BM and blood Cts were associated with PFS independently of clinical disease and MYCN gene status (p<0.001; p=0.055). <br /><br />Conclusions: This five-gene NB5 assay for NB-mRNA improves definition of disease status and correlates independently with PFS in relapsed/refractory NB.
Background: Peptic ulcer diseases are common and are induced by many factors, including stress, smoking, and ingestion of non-steroidal anti-inflammatory drugs. Quercetin is considered to be an anti-oxidant with healing effects on many experimental toxic injuries. The present study aimed to explore the possible effect of quercetin on acute gastric ulcer induced by indomethacin in rats.
Materials and methods: Three groups received indomethacin (30 mg/kg body weight) orally by orogastric gavage on two consecutive days. The rats received famotidine (50 mg/kg body weight), quercetin (50 mg/kg body weight), or vehicle alone for 15 consecutive days by oral gavage. The control group received no indomethacin but received vehicle for 15 days by oral gavage. The ulcer index, volume, and pH of gastric juice were measured, and the stomachs were examined by routine light microscopy.
Results: Compared with the control group, the indomethacin-treated rats showed a marked damage of the gastric mucosal surface and a high ulcer index. In the famotidine- and quercetin-treated groups, significantly increased antioxidant enzyme activities were observed. The congestion, erosions, and necrosis were reduced with mild inflammatory cell infiltration while no major damage of endothelial cells was observed in the treated rats.
Conclusions: The findings of the study show that quercetin had antioxidant effect and can protect gastric mucosa against indomethacin-induced gastric ulceration than famotidine.
Background: Despite the importance of the pyelocalyceal system in the pig as an experimental model, there is little information about this particular anatomical subject. We determined the morphological characteristics of the renal excretory system in pigs.
Materials and methods: This descriptive cross-sectional study evaluated 130 pairs of kidneys of pigs destined to slaughter. The pyelocalyceal system was subjected to injection technique — corrosion by infusion of polyester resin (85% Palatal and 15% Styrene) and subsequent infusion in potassium hydroxide (KOH) for 10 days. The significance level used was p < 0.05.
Results: The renal excretory system is characterised by the presence of type A major cranial and caudal calyxes seen in 34.3% of the kidneys (type A1 in 30% and type A2 in 4.3%). type B calyxes, corresponding to minor calyxes draining directly into the renal pelvis, were present in 65.7% of the specimens (type B1 59.2%; type B2 6.5% of the cases). The number of minor calyxes in the collector system was 7.9 ± 2.27 with statistically significant differences in side (p = 0.0047).
Conclusions: The morphometric characteristics of the kidneys in this study are slightly smaller than reported in humans. Similarly, the incidence of type A renal excretory system distribution is highest in humans and lowest in pigs. Due to its few morphological differences, the pig kidney is an excellent model for teaching- -learning processes, for research purposes, and for training of urologic applications.
Anatomic variations of axillary artery branches are commonly encountered during radiological investigation and surgical operations. Their existence can confuse interpretation of radiological results and lead to undesired complications during surgery. In this report authors describe a rare case of a subscapular arterial trunk that gave origin to thoracodorsal, circumflex scapular, posterior humeral circumflex, and lateral thoracic artery. Such a variation might cause undesired sequelae during trauma management and a variety of common flap harvesting operations including latissimus dorsi, scapular and parascapular flaps. Furthermore it presents embryological interest as it gives insight to embryologic development of axillary area.
The lateral circumflex femoral artery (LCFA) is responsible for vascularisation of the head and neck of the femur, greater trochanter, vastus lateralis and the knee. The origin of the LCFA has been reported to vary significantly throughout the literature, with numerous branching patterns described and variable distances to the mid-inguinal point reported. The aim of this study was to determine the estimated population prevalence and pooled means of these anatomical characteristics, and review their associated clinical relevance. A search of the major electronic databases was performed to identify all articles reporting data on the origin of the lateral circumflex femoral artery and its distance to the mid-inguinal point. Additionally, an extensive search of the references of all relevant articles was performed. All data on origin, branching, and distance to mid-inguinal point was extracted and pooled into a meta-analysis. A total of 26 articles (n = 3731 lower limbs) were included in the meta-analysis. Lateral circumflex femoral artery most commonly originates from the deep femoral artery with a pooled prevalence of 76.1% (95% confidence interval 69.4–79.3). The deep femoral artery-derived lateral circumflex femoral artery was found to originate with a mean pooled distance of 51.06 mm (95% confidence interval 44.61–57.51 mm) from the mid-inguinal point. Subgroup analysis of both gender and limb side data were consistent with these findings. Due to variability in the lateral circumflex femoral artery’s origin and distance to mid-inguinal point, anatomical knowledge is crucial for clinicians to avoid iatrogenic injuries when performing procedures in the femoral region, and thus radiographic assessment prior to surgery is recommended. Lastly, we propose a new classification system for origin of the lateral circumflex femoral artery
Background: The carotid canal (CC) located in the petrous temporal bone transmits the internal carotid artery, internal carotid venous plexus and sympathetic nerve plexus from the neck into the cranial cavity. It is an accessible passage into the cranial cavity and is considered an important anatomical landmark for neurosurgeons. The aim of this study was to investigate the topographical, morphometric and morphological parameters of the CC.
Materials and methods: An examination of the CC and related adjacent structures in 81 dry skull specimens was performed. Distribution of sample by sex was 34 females and 47 males, and by race 77 African and 4 Caucasian. The mean age was 50 years (range: 14–100 years).
Results: The external opening of the CC was found to be round-shaped, oval-shaped and tear-drop-shaped in 28.4%, 49.4% and 22.2% of the specimens, respectively. (1) Mean diameters [mm]: (a) medio-lateral 7.52 mm and (b) antero-posterior 5.41mm. Statistically significant difference in the vertical diameter was recorded in the race groups and laterality of the samples. (2) Mean distances [mm] between: (a) medial margins of external opening of CC was 50.03 mm, (b) lateral margins of external opening of CC was 62.73 mm and (c) external openings of CC and foramen lacerum was 15.6 mm. There was a statistically significant correlation between race and location of the opening of external CC in relation to foramen lacerum (viz. postero-lateral, lateral and diagonal, and lateral).
Conclusions: The present study corroborated previous reports on the CC; however, the tear-drop shaped external CC opening was a unique finding. The knowledge of the reference measurements pertaining to the CC and its relationship to adjacent structures may postulate a suitable surgical “safe-zone” range within the CC area.
A correct, exact, concise and detailed anatomical nomenclature is a cornerstone of communication not only in anatomy and related subjects but also in other medical branches and in the whole medical education. Terminologia Anatomica fulfils this task but some important structures are still missing there. The authors have collected and present here a list of terms including their definitions or explanations to provoke discussion about possible extension of the Terminologia Anatomica. The first part of this contribution, presented in this article, comprises 113 terms concerning the regulation systems of the human body: endocrine glands, central and peripheral nervous system, and senses. It also contains some corrections of anatomical mistakes, systemic inconsistencies and grammar changes.
Enthesopathy is considered to be an osseous phenomenon, either disease-specific or bone-site specific, which occurs at the enthesis of bone. Upon routine cadaveric dissection of the glenohumeral region in two Caucasian females, enthesopathy of the right proximal humerus was observed unilaterally in both cases. Case 1 exhibited an inconsistent pattern of bony protuberances and crests dispersed across the lesser and greater tuberosities of the right humeral head. Varying degrees of ossification of the distal subscapularis muscle was also observed. Case 2 presented with a distinctively large enthesophyte that protruded supero-medially from the proximal right humerus. In addition, ossification of the distal-most aspect of the supraspinatus muscle was identified. Cases 1 and 2 were both reflective of osteophytic enthesopathy as proliferative change was clearly visible on the proximal aspect of each humerus. Whilst the presence of enthesopathies may be indicative of underlying pathology, it may prove beneficial to the field of bioarchaeology for the remodelling of lifestyles of ancient civilizations through the provision of current day variations as seen in these two case studies.
Background: Internal auditory canal (IAC) stenosis and vestibulocochlear nerve (VCN) abnormalities have been reported to be associated with sensorineural hearing loss. Previous studies classified the normal dimensions of the IAC and its anomalies with no consideration of the VCN. Other studies categorised the VCN development in only stenotic canals. In the present study, an anatomical classification of the normal dimensions of the IAC and its anomalies and their association with malformations of the VCN and its subdivisions were described.
Materials and methods: Retrospective review was undertaken for children ranged from 1 to 10 years. A total of 764 canals were investigated for pre-operative assessment of cochlear implantation. Other 100 canals of normal hearing ears were included as the control group. The maximum anteroposterior diameter, considered the width of the canal, was measured in axial plane and the length of the canal was identified in coronal plane. The canals were categorised normal: if they are from 3 to 8 mm, patulous: if they are more than 8 mm, stenotic: if they are less than 3 mm and atretic if absent, using multislice computed tomography. The VCN trunks and their subdivisions were investigated using magnetic resonance imaging.
Results: Internal auditory canals were found normal in 66% with a mean width: 5.27 ± ± 0.68, patulous in 17% with a mean width 113% more than that of the control group (p = 0.000), stenotic in 13% with a mean width 73% less as compared to that of the control group (p = 0.000) and atretic in 4% of the experimental canals. The VCN trunks were found normal with well-developed subdivisions in 77.8% of the normal canals, 98.4% of the patulous canals, and 19.2% of the stenotic canals. The VCN trunks were normal with hypoplastic subdivisions in 11.3% of the normal canals, 1.6% in the patulous canals, and 61.6% in the stenotic canals with a mean width 52% less than that of the normal trunk with developed subdivisions. Hypoplastic VCN trunks with absent subdivisions were reported in 7.3% of the normal canals, 11.1% of the stenotic canals and in 3.2% of the atretic canals. The VCN trunks were not found in 3.6% of the normal canals, in 8.1% of the stenotic canals and in 96.8% of the atretic canals.
Conclusions: Internal auditory canal formation was dependent on the process of development and growth of the eighth cranial nerve and its subdivisions that greatly affected the completion of IAC canalisation. This paper could serve as a reference providing a quantitative classification of the relationship between the dimensions of the IAC and the development of the VCN trunk and its subdivisions.
Background: The “critical zone”, a region of speculated vascularity, is situated approximately 10 mm proximal to the insertion of the supraspinatus tendon. Despite its obvious role as an anatomical landmark demarcator, its patho-anatomic nature has been identified as the source of rotator cuff pathology. Although many studies have attempted to evaluate the vascularity of this region, the architecture regarding the exact length, width and shape of the critical zone, remains unreported. This study aimed to determine the shape and morphometry of the “critical zone” arthroscopically.
Materials and methods: The sample series, which was comprised of 38 cases (n = 38) specific to pathological types, employed an anatomical investigation of the critical zone during routine real-time arthroscopy. Demographic representation: i) sex: 19 males, 19 females; ii) age range: 18–76 years; iii) race: white (n = 29), Indian (n = 7) and coloured (n = 2).
Results: The incidence of shape and the mean lengths and widths of the critical zone were determined in accordance with the relevant demographic factors and patient history. Although the cresenteric shape was predominant, hemispheric and sail-shaped critical zones were also identified. The lengths and widths of the critical zone appeared markedly increased in male individuals. While the increase in age may account for the increased incidence of rotator cuff degeneration due to poor end-vascular supply, the additional factors of height and weight presented as major determinants of the increase in size of the critical zone.
Conclusions: In addition, the comparisons of length and width with each other and shape yielded levels of significant difference, therefore indicating a directly proportional relationship between the length and width of the critical zone. This detailed understanding of the critical zone may prove beneficial for the success of post-operative rotator cuff healing.
The visual cell of the retina in the Korean loach Kichulchoia multifasciata, a bottom-dwelling freshwater loach in shallow water, contains double cones and large rods. With light microscopy, the cones form a row mosaic pattern in which the partners of double cones are linearly oriented with a large rod. In a double cone or twin cone, the two members are unequal such that one cone may be longer than the other. An anatomical unit is apparent which consists of 5 rod cells and 15 double cone cells per 20 × 20 μm area. We found that the cone cells of outer segments are linked to the inner segment by so-called “calyceal process” using a scanning electron microscopy, unlike rod cells. In the transmission electron microscopy, the outer membrane shows piles of membrane discs surrounded by double membranes.
Background: Clinical detection of anatomic narrowing of the upper airway may facilitate early recognition of obstructive sleep apnoea (OSA). The aim of this study was to investigate whether anthropometric measurement can be used to predict OSA.
Materials and methods: One hundred forty-seven subject were included from those patients who were referred to our sleep laboratory with suspected sleep apnoea. All patients were divided two groups with respect to the apnoea-hypopnoea index (AHI). The first group was diagnosed as OSA, AHI greater than 5. The second group was not diagnosed with OSA, AHI less than 5 (non-OSA control). Anthropometric measurements such as lower face height (LFH), interincisial distance, nose height, anterior neck height (ANH), lateral neck height, posterior neck height (PNH), ramus mandible height, corpus mandible height (CML), bigonial distance (BGD), neck width, and neck depth were assessed.
Results: Patients with OSA had higher body mass index (BMI) and larger LFH, ANH, thyromental distance, CML, BGD, and neck circumference than those without OSA (p < 0.0001, p < 0.0001, p < 0.0001, p < 0.0001, p < 0.0001, p = 0.023, p < 0.0001, respectively). There was no difference between the two groups in terms of other parameters.
Conclusions: In this study, it was determined that BMI, lower face height, neck height, mandible length, bigonial width, thyromental distance and neck circumference are in significant relationship with sleep disordered breathing. Thus, these measurements may be used in clinical practice for prediction of OSA.
Background: In obstructive coronary artery disease, coronary collateral arteries serve as alternative conduits for blood flow to the myocardial tissue supplied by the obstructed vessel(s). Therefore, they are a “natural coronary arterial bypass” to the region supplied by the obstructed vessels. This study aims to determine the influence of demographic and morphologic coronary arterial factors on coronary collateral development in coronary arterial obstruction.
Materials and methods: The study group was selected from the coronary angiographic records of 2029 consecutive patients (mean age: 59 ± 12 years). Coronary collaterals were graded from 0 to 3 based on the collateral connection between the donor and recipient arteries. The angiograms of the patients (n = 286) with total obstruction of the coronary arteries were selected for analysis.
Results: There were no significant association between patients’ age and sex and the formation of excellent collaterals. However, the location of atherosclerotic lesion affected collateral development in the right coronary artery. In addition, the right coronary arterial dominant pattern significantly influenced the formation of excellent coronary collaterals.
Conclusions: Coronary collateral arteries are better developed in right dominant pattern. It may be concluded that coronary arterial morphological pattern influences coronary collateral artery development.
Arachnoid granulations are hypertrophied arachnoid villi, which extend from the subarachnoid space into the venous system and aid in the passive filtration and reabsorption of cerebrospinal fluid. These macroscopic structures have been described in various locations, with the transverse and sigmoid sinuses seen as normal variants on imaging. Here we present the occurrence of an enlarged arachnoid granulation at the foramen rotundum where a variant intracranial venous sinus was identified during routine dissection. Variations, such as the one described herein, should be recognised by those who operate or interpret images of the skull base.
Background: An understanding of the left main coronary artery (LMCA) anatomy is important for accurate diagnosis and therapy. We aimed to investigate LMCA anatomy via 128-multisliced coronary computed-tomography-angiography (CCTA) in patients with normal LMCA.
Materials and methods: A total of 201 CCTA studies were included in this study. Anatomical features of LMCA including cross-sectional areas of the LMCA ostial, LMCA distal, left anterior descending artery (LAD) ostial and left circumflex artery (LCX) ostial, and degree of tapering and LMCA bifurcation angles (BA) in the form of LMCA-LCX BA, LMCA-LAD BA, LAD-LCX BA at end-diastole and end-systole.
Results: The mean age was 55 ± 11; 55.7% of patients were males. Right coronary artery was dominant in 173 (86.1%) patients. Mean LMCA length was 10.0 ± 4.5 mm. The mean values of LMCA ostial, LMCA distal, LAD ostial and LCX ostial areas were 18.2 ± 5.1 mm2, 13.2 ± 4.0 mm2, 9.0 ± 3.2 mm2 and 7.6 ± ± 2.8 mm2, respectively. LMCA ostial-distal area, LMCA distal-LAD ostial area and LMCA distal-LCX ostial area ratios were ≥ 1.44 – < 1.69 in 47 (23.4%), 53 (26.4%), 47 (23.4%) patients, respectively, and were ≥ 1.69 – < 1.96 in 19 (9.5%), 24 (11.9%), 40 (19.9%) patients respectively. Systolic motion modifies LMCA BAs; systolic motion begets an increment of LMCA-LAD angle in 72.6% of patients and decrement of LAD-LCX angle in 75.6% of patients. Patients with T-shaped LAD-LCX BA was shown to have significantly longer LMCA, larger LAD ostial area, larger LCX ostial area and higher diastolic-to-systolic range (DSR) of LAD-LCX BA compared to patients with Y-shaped LAD-LCX BA.
Conclusions: LMCA with T-shaped distal BA was found to have significantly longer LMCA, larger LAD ostial area, larger LCX ostial area and higher DSR of distal BA compared to patients with Y-shaped distal BA. These findings may provide useful information for LMCA bifurcation stenting or designing dedicated stents for LMCA.
The plantaris muscle usually begins with a short and small muscle belly on the popliteal surface of the femur and on the knee joint capsule. It continues distally to form a long and thin tendon typically fixed to the calcaneal tuberosity. However, the course and the insertion of the plantaris muscle is variable, which may influence the development of Achilles tendinopathy. The plantaris tendon may also be used for reconstruction of tendons and ligaments, such as talofibular and calcaneofibular ligament. In literature review no data concerning the co-occurrence of anatomic variations of the plantaris muscle tendon in different individuals has been found. This report presents a rare variant of the plantaris muscle insertion into the deep crural fascia on the left leg and absence of the plantaris muscle on the right leg of the same individual.
Background: Congenital anomalies of the coronary arteries (CAs) are rare and are often diagnosed incidentally during a conventional coronary angiography. Recently, the incidence of these congenital defects is on the rise particularly after the introduction of the electrocardiography (ECG) gated coronary computed tomographic angiography (CCTA). This innovative radiological screening modality has led to the most precise mapping of the course of the CAs on computed tomographic scan. The aim of the study is to determine the prevalence and describe the CAs congenital anomalies and their variations in Kuwaiti population at a single institution experience.
Materials and methods: We analysed the CCTA data obtained consecutively from 842 patients (2013–2014), retrospectively. The inclusion criteria for patients’ selection were: atypical chest pain, equivocal ECG, assessment of patency of coronary stents or grafts and pre-operative screening. Information was acquiesced using a dual-source CT scanner with ECG gating.
Results: Data analysis revealed that 22 (2.61%) patients were found to have CA anomalies out of the 842 patients who underwent CCTA. Out of these CA anomalies, 13 cases showed more than two ostia, 7 cases showed the ectopic origin of a CA from opposite sinus or non-aortic sinus, 2 cases showed single coronary ostium and 1 case showed coronary artery with pulmonary fistula. Also, myocardial bridging was identified in 78 (9.26%) patients whereas ramus intermedius branch was identified in 160 (19%) patients.
Conclusions: The prevalence of CA anomalies in Kuwait was 2.6%, which is relatively higher than previously reported studies from different countries.
Background: Antlers are lined by soft velvet tissue during antler growth. Later, the velvet is shed before rut onset. There are no detailed histological descriptions of the growing velvet, nor whether the velvet changes according to stag age. Our aims were to: 1) describe the basic histology of pampas deer antler velvet from adult and yearling males; and 2) determine the influence of age and time of antler growth on velvet’s tissues morphometry.
Materials and methods: Samples were collected from 10 stags allocated in two groups, either adult (3–5 years old, n = 5) or yearling males (2 years old, n = 5). The day of antler cast was recorded for each animal. In spring, the stags were anaesthetised and velvet samples were collected from the third tine’s distal end. Samples were described qualitatively and a restricted morphometrical analysis of the antler velvet was performed.
Results: The number of keratinocyte layers and the thicknesses of: total epidermis, corneum, intermediate and basale epidermal strata, total dermis, superficial and deep dermis were determined. Age and days after antler casting positively influenced in conjunction epidermal thickness (p = 0.037), and tended to influence both stratum intermedium (p = 0.076) and stratum corneum (p = 0.1) thicknesses. Age influenced stratum corneum thickness (p = 0.04). The pampas deer antler velvet lacked both sweat glands and arrector pili muscles.
Conclusions: The deep dermis was densely irrigated but displayed abundant and well developed collagen bundles. Both total epidermal and stratum corneum thicknesses related positively to the age of the animals but were not to the time since antler cast.
Background: The superficial palmar arch (SPA) and deep palmar arch (DPA) provide the dominant vascular supply to the hand. The SPA is considered to be highly variable and can be classified as either complete or incomplete. The simplest definition states that the anastomosis between the vessels contributing to the arch represent a complete arch, while an incomplete arch is described as characterised by an absence of anastomosis between the vessels contributing to it. This study aimed to describe the anatomical landmarks, formation and branching patterns of the SPA and DPA. In this study, the SPA and DPA were dissected in 50 specimens (n = 100 adult hands), respectively.
Materials and methods: A complete SPA was observed in 92% of specimens and classified into three types. In Type A (44%), the SPA was formed by the anastomosis of the superficial palmar branch of the radial artery with the ulnar artery. Type B (46%) was formed by the ulnar artery alone and Type C (2%) was formed by anastomosis of the ulnar artery with the superficial palmar branch of the radial artery and the persistent median artery.
Results: An incomplete SPA was observed in 8% of the specimens and divided into three types formed by the radial and ulnar arteries. The DPA was divided into five types viz. Type G (72%), where the DPA was formed by anastomosis of the deep palmar branch of the radial artery (DPBRA) with the deep palmar branch of the ulnar artery (DPBUA). Type H (12%), was formed by anastomosis of the DPBRA, the DBUA and the interosseous artery. Type I (8%), was formed by the anastomosis of the DPBRA with the superior and inferior DPBUA. Type J (4%), the deep ulnar artery had two branches whereby either one branch anastomosed with the DPBRA to form the DPA. Type K (4%), the DBUA exhibited two deep branches with one branch anastomosing with the DPBRA to complete the DPA.
Conclusions: The interosseous artery anastomosed with either the DPA or the additional DPBUA. Knowledge of the variability of the SPA and DPA is crucial for safe and successful hand surgeries.
Background: The aim of the work was to perform a morphometric analysis of the long peroneal muscle (LPM) of the leg and explore the relationship between muscle belly and tendon.
Materials and methods: Ten lower limbs (8 right and 2 left) were fixed in formaldehyde and dissected using standard technique. The LPM was exposed from the proximal attachment to the top of a lateral malleolus.
Results: The tendon was subsequently freed and various measurements were taken. The tendon of the LPM enters deep into the muscle belly. Muscle fibres surround the tendon and descend as far down as 4 cm above the lateral malleolus. Muscle fibres insert mainly along posterior border of the tendon and on its medial surface, leaving lateral surface only partly covered.
Conclusions: The LPM contains a long intramuscular segment of the tendon and area of the musculotendinous junction varies along the LPM. It makes the idea of uniform pennation pattern of the LPM unlikely
Background: The aim of the study was to determine the incidence of multiple kidney arteries in the Polish population.
Materials and methods: The study group comprised 924 deceased patients aged between 1 month and 94 years (mean age: 63.4 ± 22.4 years) who were subject to aortonephrography and sample preparation. The ratio of male to female patients was 479:445.
Results: Multiple kidney arteries were observed in 44.8% male and 31.5% female patients (p = 0.004). Considering male patients, right multiple kidney arteries were diagnosed in 24.4%, and left multiple kidney arteries in 31.3% of cases (p = 0.017). In female patients, right multiple kidney arteries were observed in 17.8% of cases, and left multiple kidney arteries in 19.6% of cases (p = 0.49).
Conclusions: The incidence of multiple kidney arteries in the Polish population is a frequent phenomenon, and should be considered in case of urological surgery and kidney transplantation.
The results of meta-analyses are frequently reported, but understanding and interpreting them is difficult for both clinicians and patients. Statistical significances are presented without referring to values that imply clinical relevance.
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Radiofrequency denervation is commonly used for the treatment of chronic facet joint pain that has been refractory to more conservative treatments, although the evidence supporting this treatment has been controversial.
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The epithelial-to-mesenchymal transition (EMT) is a biological process in which a non-motile epithelial cell changes to a mesenchymal state with invasive capacities. However, the EMT program is involved in both physiological and pathological processes. Cancer-associated EMT is known to contribute to increase invasiveness and metastasis, resistance to therapies, and generation of cell populations with stem cell-like characteristics and therefore is deeply involved in tumor progression. This process is finely orchestrated by multiple signaling pathways and regulatory transcriptional networks. The hallmark of EMT is the loss of epithelial surface markers, mainly E-cadherin, and the acquisition of mesenchymal phenotype. These events can be mediated by EMT transcription factors which can cooperate with several enzymes to repress the E-cadherin expression and regulate EMT at the epigenetic and post-translational level. A growing body of evidence indicates that cancer cells can reside in various phenotypic states along the EMT spectrum, where cells can jointly retain epithelial traits with mesenchymal ones. This type of phenotypic plasticity endows cancer cells with tumor-initiating potential. The identification of the signaling pathways and modulators that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
The interval between surgery and adjuvant chemotherapy (AC) is a predictive factor of survival in high-risk colon cancer (CC). This study aimed to evaluate the impact of intraoperative sentinel lymph node (SLN) analysis using the one-step nucleic acid amplification (OSNA) technique on the time interval between surgery and AC.
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J reconstr Microsurg
DOI: 10.1055/s-0037-1603351
Introduction Breast reconstruction using deep inferior epigastric artery perforator (DIEP) free flap is widely used because of the advantages of minimizing donor-site morbidity, but it requires technical competency in vascular dissection. This study evaluated the influence of patient factors and vascular status on the time and speed of dissection of the vascular pedicle. Methods DIEP free flap procedures were performed in 49 patients assigned to immediate or delayed reconstruction groups. Factors that significantly influenced the time required and the speed of dissection were evaluated. Results The average total dissection time was 55.9 minutes (34.5 minutes for the intramuscular dissection and 21.4 minutes for the submuscular dissection). The dissection speed for the total vascular pedicle was 2.65 cm/10 minutes (1.71 cm/10 minutes for the intramuscular dissection and 4.30 cm/10 minutes for the submuscular dissection). The presence of a Pfannenstiel scar, length of the vascular pedicle in the intramuscular area, and the number of microclips used significantly correlated with the total dissection time. Conclusion The length of the intramuscular pedicle, number of microclips used, and presence of a Pfannenstiel scar significantly correlated with the total dissection time of the vascular pedicle. An assessment prior to the surgery can reduce the time of operation and make it easier to elevate the flap.
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Table of contents | Abstract | Full text
The interval between surgery and adjuvant chemotherapy (AC) is a predictive factor of survival in high-risk colon cancer (CC). This study aimed to evaluate the impact of intraoperative sentinel lymph node (SLN) analysis using the one-step nucleic acid amplification (OSNA) technique on the time interval between surgery and AC.
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To analyze the procedural and clinical outcomes of carotid artery stenting (CAS) in the hands of endovascular trained vascular surgeons.
Between April 2008 to May 2013, 1197 patients were treated for extracranial internal carotid artery (ICA) stenosis. The proportion of endovascular treated patients was 5.0% (CAS n = 60 vs. carotid endarterectomy (CEA) n = 1137). All patients in the CAS group (44 males, median age 70 years) were treated by two senior vascular surgeons experienced in endovascular methods. Restenosis was the indication for CAS in 32 out of 60 patients (53.3%). Further indications were contralateral ICA occlusion (n = 14, 23.3%), radiogenic ICA stenosis (n = 5, 8.3%), high-risk candidates for CEA (n = 4, 6.6%), and the presence of contralateral recurrent paresis (n = 2, 3.3%). High-risk patients for CEA were defined as patients with history of severe cardiac disease and patients with impaired general condition. 84.4% (n = 27) of the restenosis were asymptomatic with a mean degree of stenosis of 83.7%, and 12.9% (n = 4) were symptomatic (degree of stenosis of 90%). Mean procedural and fluoroscopy time were 61 and 14 min. Study endpoints were periprocedural stroke-related mortality and morbidity, restenosis rate, and overall survival. Follow-up was performed by duplex ultrasound with a median follow-up period of 12 months (range 1–55).
The periprocedural stroke rate of CAS within 30 days was 3.3% (one ischemic stroke, one intracranial hemorrhage); two additional patients suffered TIA (3.3%). None of the patients had a myocardial infarction perioperatively. The mortality rate was 0. CAS procedures were completed in 90.0% (n = 54) of cases. Dropout rate was 8.3% (n = 5) for morphological reasons (e.g., carotid kinking). Intraoperative complication rate was 1.7% (n = 1) including one patient who suffered intraoperative rupture of access vessels. The conversion rate with subsequent CEA procedure was 6.6% (n = 4 of 5). The restenosis rate during follow-up was 3.3% after CAS. The reintervention rate during the median follow-up period of 12 months (1–55 months) was 5.5% (n = 3/54). Two patients received a reintervention with successful balloon angioplasty; in one case, a diagnostic angiography was performed excluding the presence of a relevant restenosis. No additional stent was implanted. The survival rate was 100% at 1 year, 90.4% at 2 years, and 77.7% at 3 years.
CAS, in the hands of vascular surgeons, is feasible with a moderate perioperative risk in a highly selected patient cohort. A procedure termination rate of approximately 10% shows that the complementary therapy using CAS procedure is not overused by surgeons.
Melanocytic BAP1-associated intradermal tumors (MBAITs) can either be sporadic or associated with a cancer-predisposition syndrome. In this study we explored the clinical status of 136 patients in which at least one MBAIT was found. 49/136 (36%) of them gave their signed consent for an oncogenetic BAP1 blood test. 28/136 patients (20%) diagnosed with an MBAIT had other MBAITs and/or a personal or familial history of BAP1-related cancers that could clinically designate them as potential carriers of a BAP1 germline mutation. 17 of these 28 patients underwent oncogenetic testing. A deleterious mutation of BAP1 was confirmed in 12/17 cases. 4/17 cases were wild-type; all had a single MBAIT and a history of skin melanoma. A variant of unknown significance was found in one case with multiple MBAITs. Among the 12 mutated cases, multiple MBAITs were present in 10/12 cases and were the only clinical sign in 4/12 cases. The remaining 32/49 blood-tested cases with an isolated MBAIT were wild type for BAP1 in 25/32 cases or showed a variant of unknown significance in 7/32 cases. We recommend, following the diagnosis of a MBAIT, performing a BAP1 immunohistochemistry in all other cutaneous melanocytic tumors removed previously or simultaneously and all skin melanomas. This screening could help clinicians prioritize which patients would most benefit from oncogenetic testing. This article is protected by copyright. All rights reserved.
PET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical 18F-FET PET reading.
The background activity of 20 18F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans.
Compared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more.
The commonly applied methods for background activity assessment show different variability which might hamper 18F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a (guided) crescent-shaped VOI allows minimization of both intra- and inter-reader variability and might facilitate comprehensive methodological standardization of amino acid PET which is of interest in the light of the anticipated EANM technical guidelines.
The ability to image vascular endothelial growth factor (VEGF) could enable prospective, non-invasive monitoring of patients receiving anti-angiogenic therapy. This study investigates the specificity and pharmacokinetics of 111In-bevacizumab binding to VEGF and its use for assessing response to anti-angiogenic therapy with rapamycin.
Specificity of 111In-bevacizumab binding to VEGF was tested in vitro with unmodified radiolabelled bevacizumab in competitive inhibition assays. Uptake of 111In-bevacizumab in BALB/c nude mice bearing tumours with different amounts of VEGF expression was compared to that of isotype-matched control antibody (111In-IgG1κ) with an excess of unlabelled bevacizumab. Intratumoural VEGF was evaluated using ELISA and Western blot analysis. The effect of anti-angiogenesis therapy was tested by measuring tumour uptake of 111In-bevacizumab in comparison to 111In-IgG1κ following administration of rapamycin to mice bearing FaDu xenografts. Uptake was measured using gamma counting of ex vivo tumours and effect on vasculature by using anti-CD31 microscopy.
Specific uptake of 111In-bevacizumab in VEGF-expressing tumours was observed. Rapamycin led to tumour growth delay associated with increased relative vessel size (8.5 to 10.3, P = 0.045) and decreased mean relative vessel density (0.27 to 0.22, P = 0.0015). Rapamycin treatment increased tumour uptake of 111In-bevacizumab (68%) but not 111In-IgGκ and corresponded with increased intratumoural VEGF165.
111In-bevacizumab accumulates specifically in VEGF-expressing tumours, and changes after rapamycin therapy reflect changes in VEGF expression. Antagonism of mTOR may increase VEGF in vivo, and this new finding provides the basis to consider combination studies blocking both pathways and a way to monitor effects.
