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Critical Care (London, England) Jul 2019Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is an increasingly adopted life-saving mechanical circulatory support for a number of potentially reversible... (Review)
Review
Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is an increasingly adopted life-saving mechanical circulatory support for a number of potentially reversible or treatable cardiac diseases. It is also started as a bridge-to-transplantation/ventricular assist device in the case of unrecoverable cardiac or cardio-respiratory illness. In recent years, principally for non-post-cardiotomy shock, peripheral cannulation using the femoral vessels has been the approach of choice because it does not need the chest opening, can be quickly established, can be applied percutaneously, and is less likely to cause bleeding and infections than central cannulation. Peripheral ECMO, however, is characterized by a higher rate of vascular complications. The mechanisms of such adverse events are often multifactorial, including suboptimal arterial perfusion and hemodynamic instability due to the underlying disease, peripheral vascular disease, and placement of cannulas that nearly occlude the vessel. The effect of femoral artery damage and/or significant reduced limb perfusion can be devastating because limb ischemia can lead to compartment syndrome, requiring fasciotomy and, occasionally, even limb amputation, thereby negatively impacting hospital stay, long-term functional outcomes, and survival. Data on this topic are highly fragmentary, and there are no clear-cut recommendations. Accordingly, the strategies adopted to cope with this complication vary a great deal, ranging from preventive placement of antegrade distal perfusion cannulas to rescue interventions and vascular surgery after the complication has manifested.This review aims to provide a comprehensive overview of limb ischemia during femoral cannulation for VA-ECMO in adults, focusing on incidence, tools for early diagnosis, risk factors, and preventive and treating strategies.
Topics: Catheterization, Peripheral; Extracorporeal Membrane Oxygenation; Extremities; Humans; Incidence; Ischemia; Risk Factors
PubMed: 31362770
DOI: 10.1186/s13054-019-2541-3 -
Skeletal Radiology Apr 2019Following the thalidomide disaster (1958-62), Henkel and Willert analysed the pattern of dysmelia in the long bones (J Bone Joint Surg Br. 51:399-414, 1969) and the... (Review)
Review
BACKGROUND
Following the thalidomide disaster (1958-62), Henkel and Willert analysed the pattern of dysmelia in the long bones (J Bone Joint Surg Br. 51:399-414, 1969) and the extremities, Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970). Willert's material from deformed extremities is re-examined here asking "How does thalidomide reduce the skeleton?"
MATERIALS AND METHODS
We reviewed the original data collection of Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), comprising musculoskeletal histology slides from 30 children affected by thalidomide with radiographs of hands (19 cases) and feet (4 cases).
RESULTS
All original observations by Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), were verified. Radial rays of the hand disappeared early, but the foot was spared until late. Radiology confirms that bone reduction in the hand (aplasia or hypoplasia in the thumb and index finger) coincides with sensory segmental nerve C6. In the foot, reduction of the toes is rare, but mesenchymal excess (polydactyly) occurs in the hallux (L5 sclerotome), usually associated with absent tibia (L4 sclerotome). Histology confirms skeletal mesenchymal components to be unremarkable, contrasting with grossly abnormal bony architecture, a striking discordance between microscopic and macroscopic findings. No necrosis or vascular pathology was seen.
CONCLUSION
The basic lesion was an abnormal quantity rather than quality of mesenchyme. Cell populations result from cellular proliferation, controlled in early limb bud formation by neurotrophism. Thalidomide is a known sensory neurotoxin in adults. In the embryo, sensorineural injury alters neurotrophism, causing increased or diminished cell proliferation in undifferentiated mesenchyme. Differentiation into normal cartilage occurs later, but within an altered mesenchymal mass. Reduction or excess deformity results, with normal histology, a significant finding. The primary pathological condition is not in the skeleton, but in the nerves.
Topics: Abnormalities, Drug-Induced; Extremities; Humans; Infant, Newborn; Limb Deformities, Congenital; Peripheral Nervous System Diseases; Thalidomide
PubMed: 30341712
DOI: 10.1007/s00256-018-3086-2 -
Developmental Dynamics : An Official... May 2011While the paired forelimb and hindlimb buds of vertebrates are initially morphologically homogeneous, as the limb progenitors differentiate, each individual tissue... (Review)
Review
While the paired forelimb and hindlimb buds of vertebrates are initially morphologically homogeneous, as the limb progenitors differentiate, each individual tissue element attains a characteristic limb-type morphology that ultimately defines the constitution of the forelimb or hindlimb. This review focuses on contemporary understanding of the regulation of limb bud initiation and formation of limb-type specific morphologies and how these regulatory mechanisms evolved in vertebrates. We also attempt to clarify the definition of the terms limb-type identity and limb-type morphology that have frequently been used interchangeably. Over the last decade, three genes, Tbx4, Tbx5, and Pitx1, have been extensively studied for their roles in limb initiation and determining limb-type morphologies. The role of Tbx4 and Tbx5 in limb initiation is clearly established. However, their putative role in the generation of limb-type morphologies remains controversial. In contrast, all evidence supports a function for Pitx1 in determination of hindlimb morphologies.
Topics: Animals; Extremities; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Humans; Limb Buds; Morphogenesis; T-Box Domain Proteins
PubMed: 21360788
DOI: 10.1002/dvdy.22582 -
Developmental Biology Sep 2017Vertebrate limb development relies on the activity of signaling centers that promote growth and control patterning along three orthogonal axes of the limb bud. The... (Review)
Review
Vertebrate limb development relies on the activity of signaling centers that promote growth and control patterning along three orthogonal axes of the limb bud. The apical ectodermal ridge, at the distal rim of the limb bud ectoderm, produces WNT and FGF signals, which promote limb bud growth and progressive distalization. The zone of polarizing activity, a discrete postero-distal mesenchymal domain, produces SHH, which stimulates growth and organizes patterning along the antero-posterior axis. The dorsal and ventral ectoderms produce, respectively, WNT7A and BMPs, which induce dorso-ventral limb fates. Interestingly, these signaling centers and the mechanisms they instruct interact with each other to coordinate events along the three axes. We review here the main interactions described between the three axial systems of the developing limb and discuss their relevance to proper limb growth and patterning.
Topics: Animals; Body Patterning; Extremities; Models, Biological; Signal Transduction
PubMed: 28283405
DOI: 10.1016/j.ydbio.2017.03.006 -
Journal of Anatomy Oct 2015The vertebrate limb with its complex anatomy develops from a small bud of undifferentiated mesoderm cells encased in ectoderm. The bud has its own intrinsic polarity and... (Review)
Review
The vertebrate limb with its complex anatomy develops from a small bud of undifferentiated mesoderm cells encased in ectoderm. The bud has its own intrinsic polarity and can develop autonomously into a limb without reference to the rest of the embryo. In this review, recent advances are integrated with classical embryology, carried out mainly in chick embryos, to present an overview of how the embryo makes a limb bud. We will focus on how mesoderm cells in precise locations in the embryo become determined to form a limb and express the key transcription factors Tbx4 (leg/hindlimb) or Tbx5 (wing/forelimb). These Tbx transcription factors have equivalent functions in the control of bud formation by initiating a signalling cascade involving Wnts and fibroblast growth factors (FGFs) and by regulating recruitment of mesenchymal cells from the coelomic epithelium into the bud. The mesoderm that will form limb buds and the polarity of the buds is determined with respect to both antero-posterior and dorso-ventral axes of the body. The position in which a bud develops along the antero-posterior axis of the body will also determine its identity - wing/forelimb or leg/hindlimb. Hox gene activity, under the influence of retinoic acid signalling, is directly linked with the initiation of Tbx5 gene expression in the region along the antero-posterior axis of the body that will form wings/forelimbs and determines antero-posterior polarity of the buds. In contrast, Tbx4 expression in the regions that will form legs/hindlimbs is regulated by the homeoprotein Pitx1 and there is no evidence that Hox genes determine antero-posterior polarity of the buds. Bone morphogenetic protein (BMP) signalling determines the region along the dorso-ventral axis of the body in which both wings/forelimbs and legs/hindlimbs develop and dorso-ventral polarity of the buds. The polarity of the buds leads to the establishment of signalling regions - the dorsal and ventral ectoderm, producing Wnts and BMPs, respectively, the apical ectodermal ridge producing fibroblast growth factors and the polarizing region, Sonic hedgehog (Shh). These signals are the same in both wings/forelimbs and legs/hindlimbs and control growth and pattern formation by providing the mesoderm cells of the limb bud as it develops with positional information. The precise anatomy of the limb depends on the mesoderm cells in the developing bud interpreting positional information according to their identity - determined by Pitx1 in hindlimbs - and genotype. The competence to form a limb extends along the entire antero-posterior axis of the trunk - with Hox gene activity inhibiting the formation of forelimbs in the interlimb region - and also along the dorso-ventral axis.
Topics: Animals; Body Patterning; Extremities; Gene Expression Regulation, Developmental; Hedgehog Proteins; Humans; Limb Buds; Morphogenesis; Signal Transduction; Transcription Factors
PubMed: 26249743
DOI: 10.1111/joa.12361 -
Development (Cambridge, England) Sep 2020The vertebrate limb continues to serve as an influential model of growth, morphogenesis and pattern formation. With this Review, we aim to give an up-to-date picture of... (Review)
Review
The vertebrate limb continues to serve as an influential model of growth, morphogenesis and pattern formation. With this Review, we aim to give an up-to-date picture of how a population of undifferentiated cells develops into the complex pattern of the limb. Focussing largely on mouse and chick studies, we concentrate on the positioning of the limbs, the formation of the limb bud, the establishment of the principal limb axes, the specification of pattern, the integration of pattern formation with growth and the determination of digit number. We also discuss the important, but little understood, topic of how gene expression is interpreted into morphology.
Topics: Animals; Body Patterning; Extremities; Gene Expression Regulation, Developmental; Limb Buds; Vertebrates
PubMed: 32917670
DOI: 10.1242/dev.177956 -
Current Osteoporosis Reports Dec 2014In the musculoskeletal system, muscle, tendon, and bone tissues develop in a spatially and temporally coordinated manner, and integrate into a cohesive functional unit... (Review)
Review
In the musculoskeletal system, muscle, tendon, and bone tissues develop in a spatially and temporally coordinated manner, and integrate into a cohesive functional unit by forming specific connections unique to each region of the musculoskeletal system. The mechanisms of these patterning and integration events are an area of great interest in musculoskeletal biology. Hox genes are a family of important developmental regulators and play critical roles in skeletal patterning throughout the axial and appendicular skeleton. Unexpectedly, Hox genes are not expressed in the differentiated cartilage or other skeletal cells, but rather are highly expressed in the tightly associated stromal connective tissues as well as regionally expressed in tendons and muscle connective tissue. Recent work has revealed a previously unappreciated role for Hox in patterning all the musculoskeletal tissues of the limb. These observations suggest that integration of the musculoskeletal system is regulated, at least in part, by Hox function in the stromal connective tissue. This review will outline our current understanding of Hox function in patterning and integrating the musculoskeletal tissues.
Topics: Animals; Cell Differentiation; Cell Proliferation; Extremities; Genes, Homeobox; Humans; Models, Animal; Musculoskeletal Development
PubMed: 25266923
DOI: 10.1007/s11914-014-0241-0 -
Clinical and Translational Medicine Jan 2022Despite improved surgical approaches for chronic limb-threatening ischemia (CLTI), amputation rates remain high and contributing tissue-level factors remain unknown. The...
BACKGROUND
Despite improved surgical approaches for chronic limb-threatening ischemia (CLTI), amputation rates remain high and contributing tissue-level factors remain unknown. The purpose of this study was twofold: (1) to identify differences between the healthy adult and CLTI limb muscle proteome, and (2) to identify differences in the limb muscle proteome of CLTI patients prior to surgical intervention or at the time of amputation.
METHODS AND RESULTS
Gastrocnemius muscle was collected from non-ischemic controls (n = 19) and either pre-interventional surgery (n = 10) or at amputation outcome (n = 29) CLTI patients. All samples were subjected to isobaric tandem-mass-tag-assisted proteomics. The mitochondrion was the primary classification of downregulated proteins (> 70%) in CLTI limb muscles and paralleled robust functional mitochondrial impairment. Upregulated proteins (> 38%) were largely from the extracellular matrix. Across the two independent sites, 39 proteins were downregulated and 12 upregulated uniformly. Pre-interventional CLTI muscles revealed a robust upregulation of mitochondrial proteins but modest functional impairments in fatty acid oxidation as compared with controls. Comparison of pre-intervention and amputation CLTI limb muscles revealed mitochondrial proteome and functional deficits similar to that between amputation and non-ischemic controls. Interestingly, these observed changes occurred despite 62% of the amputation CLTI patients having undergone a prior surgical intervention.
CONCLUSIONS
The CLTI proteome supports failing mitochondria as a phenotype that is unique to amputation outcomes. The signature of pre-intervention CLTI muscle reveals stable mitochondrial protein abundance that is insufficient to uniformly prevent functional impairments. Taken together, these findings support the need for future longitudinal investigations aimed to determine whether mitochondrial failure is causally involved in amputation outcomes from CLTI.
Topics: Aged; Aged, 80 and over; Chronic Limb-Threatening Ischemia; Cross-Sectional Studies; Extremities; Female; Florida; Humans; Male; Muscle, Skeletal; North Carolina; Proteome; Risk Factors
PubMed: 35073463
DOI: 10.1002/ctm2.658 -
Developmental Dynamics : An Official... May 2011The experimental study of amphibian limb regeneration spans most of the 20th century and the first decade of the 21st century. We first review the major questions... (Review)
Review
The experimental study of amphibian limb regeneration spans most of the 20th century and the first decade of the 21st century. We first review the major questions investigated over this time span: (1) the origin of regeneration blastema cells, the mechanism of tissue breakdown that liberates cells from their tissue organization to participate in blastema formation, (3) the mechanism of dedifferentiation of these cells, (4) how the blastema grows, (5) how the blastema is patterned to restore the missing limb structures, and (6) why adult anurans, birds and mammals do not have the regenerative powers of urodele salamanders. We then look forward in a perspective to discuss the many unanswered questions raised by investigations of the past century, what new approaches can be taken to answer them, and what the prospects are for translation of basic research on limb regeneration into clinical means to regenerate human appendages.
Topics: Amphibians; Animals; Extremities; Humans; Regeneration
PubMed: 21290477
DOI: 10.1002/dvdy.22553 -
Scientific Reports Dec 2021The identification of movement strategies in situations that are as ecologically valid as possible is essential for the understanding of lower limb interactions. This...
The identification of movement strategies in situations that are as ecologically valid as possible is essential for the understanding of lower limb interactions. This study considered the kinetic and kinematic data for the hip, knee and ankle joints from 376 block jump-landings when moving in the dominant and non-dominant directions from fourteen senior national female volleyball players. Two Machine Learning methods were used to generate the models from the dataset, Random Forest and Artificial Neural Networks. In addition, decision trees were used to detect which variables were relevant to discern the limb movement strategies and to provide a meaningful prediction. The results showed statistically significant differences when comparing the movement strategies between limb role (accuracy > 88.0% and > 89.3%, respectively), and when moving in the different directions but performing the same role (accuracy > 92.3% and > 91.2%, respectively). This highlights the importance of considering limb dominance, limb role and direction of movement during block jump-landings in the identification of which biomechanical variables are the most influential in the movement strategies. Moreover, Machine Learning allows the exploration of how the joints of both limbs interact during sporting tasks, which could provide a greater understanding and identification of risky movements and preventative strategies. All these detailed and valuable descriptions could provide relevant information about how to improve the performance of the players and how to plan trainings in order to avoid an overload that could lead to risk of injury. This highlights that, there is a necessity to consider the learning models, in which the spike approach unilaterally is taught before the block approach (bilaterally). Therefore, we support the idea of teaching bilateral approach before learning the spike, in order to improve coordination and to avoid asymmetries between limbs.
Topics: Adult; Biomechanical Phenomena; Extremities; Female; Functional Laterality; Humans; Male; Movement; Range of Motion, Articular; Volleyball; Young Adult
PubMed: 34880343
DOI: 10.1038/s41598-021-03106-0