bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification, isolation and characterization of human LGR5-positive colon adenoma cells
Authors: Dame Michael K. , Attili Durga , McClintock Shannon D. , Dedhia Priya H. , Ouillette Peter , Hardt Olaf , Chin Alana M. , Xue Xiang , Laliberte Julie , Katz Erica L. , Newsome Gina M. , Hill David R. , Miller Alyssa J. , Tsai Yu-Hwai , Agorku David , Altheim Christopher H. , Bosio Andreas , Simon Becky , Samuelson Linda C. , Stoerker Jay A. , Appelman Henry D. , Varani James , Wicha Max S. , Brenner Dean E. , Shah Yatrik M. , Spence Jason R. , Colacino Justin A.
Published: February 2018

The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, whereas less is known about human intestinal stem cells owing to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC)-associated genes. Normal and neoplastic colon tissue organoids were analyzed by immunohistochemistry and fluorescent-activated cell sorting for LGR5. LGR5-positive cells were isolated from four adenoma organoid lines and were subjected to RNA sequencing. We found that LGR5 expression in the epithelium and stroma was associated with tumor stage, and by integrating functional experiments with LGR5-sorted cell RNA sequencing data from adenoma and normal organoids, we found correlations between LGR5 and CRC-specific genes, including dickkopf WNT signaling pathway inhibitor 4 (DKK4) and SPARC-related modular calcium binding 2 (SMOC2). Collectively, this work provides resources, methods and new markers to isolate and study stem cells in human tissue homeostasis and carcinogenesis.
Precise spatial restriction of BMP signaling in developing joints is perturbed upon loss of embryo movement
Authors: Singh Pratik Narendra Pratap , Shea Claire A. , Sonker Shashank Kumar , Rolfe Rebecca A. , Ray Ayan , Kumar Sandeep , Gupta Pankaj , Murphy Paula , Bandyopadhyay Amitabha
Published: February 2018

Dynamic mechanical loading of synovial joints is necessary for normal joint development, as evidenced in certain clinical conditions, congenital disorders and animal models where dynamic muscle contractions are reduced or absent. Although the importance of mechanical forces on joint development is unequivocal, little is known about the molecular mechanisms involved. Here, using chick and mouse embryos, we observed that molecular changes in expression of multiple genes analyzed in the absence of mechanical stimulation are consistent across species. Our results suggest that abnormal joint development in immobilized embryos involves inappropriate regulation of Wnt and BMP signaling during definition of the emerging joint territories, i.e. reduced β-catenin activation and concomitant upregulation of pSMAD1/5/8 signaling. Moreover, dynamic mechanical loading of the developing knee joint activates Smurf1 expression; our data suggest that Smurf1 insulates the joint region from pSMAD1/5/8 signaling and is essential for maintenance of joint progenitor cell fate.
Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration in part by accelerating the rate of aging
Authors: Spurrier Joshua , Shukla Arvind Kumar , McLinden Kristina , Johnson Kory , Giniger Edward
Published: February 2018

Aging is the greatest risk factor for neurodegeneration, but the connection between the two processes remains opaque. This is in part for want of a rigorous way to define physiological age, as opposed to chronological age. Here we develop a comprehensive metric for physiological age in Drosophila, based on genome-wide expression profiling. We applied this metric to a model of adult-onset neurodegeneration, increased or decreased expression of the activating subunit of the Cdk5 protein kinase, encoded by the gene Cdk5α, the ortholog of mammalian p35. Cdk5α-mediated degeneration was associated with a 27-150% acceleration of the intrinsic rate of aging, depending on the tissue and genetic manipulation. Gene ontology analysis and direct experimental tests revealed that affected, age-associated processes included numerous core phenotypes of neurodegeneration, including enhanced oxidative stress and impaired proteostasis. Taken together, our results suggest that Cdk5α-mediated neurodegeneration results from accelerated aging, in combination with cell-autonomous neuronal insults. These data fundamentally recast our picture of the relationship between neurodegeneration and its most prominent risk factor, natural aging.
RNA tales – how embryos read and discard messages from mom
Authors: Despic Vladimir , Neugebauer Karla M.
Published: February 2018

Following fertilization, embryos develop for a substantial amount of time with a transcriptionally silent genome. Thus, early development is maternally programmed, as it solely relies on RNAs and proteins that are provided by the female gamete. However, these maternal instructions are not sufficient to support later steps of embryogenesis and are therefore gradually replaced by novel products synthesized from the zygotic genome. This switch in the origin of molecular players that drive early development is known as the maternal-to-zygotic transition (MZT). MZT is a universal phenomenon among all metazoans and comprises two interconnected processes: maternal mRNA degradation and the transcriptional awakening of the zygotic genome. The recent adaptation of high-throughput methods for use in embryos has deepened our knowledge of the molecular principles underlying MZT. These mechanisms comprise conserved strategies for RNA regulation that operate in many well-studied cellular contexts but that have adapted differently to early development. In this Review, we will discuss advances in our understanding of post-transcriptional regulatory pathways that drive maternal mRNA clearance during MZT, with an emphasis on recent data in zebrafish embryos on codon-mediated mRNA decay, the contributions of microRNAs (miRNAs) and RNA-binding proteins to this process, and the roles of RNA modifications in the stability control of maternal mRNAs.
Hematopoietic stem cells from induced pluripotent stem cells – considering the role of microRNA as a cell differentiation regulator
Authors: Ferreira Aline F. , Calin George A. , Picanço-Castro Virgínia , Kashima Simone , Covas Dimas T. , de Castro Fabiola A.
Published: February 2018

Although hematopoietic stem cell (HSC) therapy for hematological diseases can lead to a good outcome from the clinical point of view, the limited number of ideal donors, the comorbidity of patients and the increasing number of elderly patients may limit the application of this therapy. HSCs can be generated from induced pluripotent stem cells (iPSCs), which requires the understanding of the bone marrow and liver niches components and function in vivo. iPSCs have been extensively applied in several studies involving disease models, drug screening and cellular replacement therapies. However, the somatic reprogramming by transcription factors is a low-efficiency process. Moreover, the reprogramming process is also regulated by microRNAs (miRNAs), which modulate the expression of the transcription factors OCT-4 (also known as POU5F1), SOX-2, KLF-4 and MYC, leading somatic cells to a pluripotent state. In this Review, we present an overview of the challenges of cell reprogramming protocols with regard to HSC generation from iPSCs, and highlight the potential role of miRNAs in cell reprogramming and in the differentiation of induced pluripotent stem cells.
Regulation of profibrotic responses by ADAM17 activation in high glucose requires its C-terminus and FAK
Authors: Li Renzhong , Wang Tony , Walia Khyati , Gao Bo , Krepinsky Joan C.
Published: February 2018

Glomerular matrix accumulation is the hallmark of diabetic nephropathy. The metalloprotease ADAM17 mediates high glucose (HG)-induced matrix production by kidney mesangial cells through release of ligands for the epidermal growth factor receptor. Here, we study the mechanism by which HG activates ADAM17. We find that the C-terminus is essential for ADAM17 activation and the profibrotic response to HG. In the C-terminus, Src-mediated Y702 phosphorylation and PI3K–MEK–Erk-mediated T735 phosphorylation are crucial for ADAM17 activation, both are also required for the HG-induced increase in cell surface mature ADAM17. The non-receptor tyrosine kinase FAK is a central mediator of these processes. These data not only support a crucial role for the C-terminus in ADAM17 activation and downstream profibrotic responses to HG, but also highlight FAK as a potential alternative therapeutic target for diabetic nephropathy.
Inflachromene inhibits autophagy through modulation of Beclin 1 activity
Authors: Kim Young Hun , Kwak Man Sup , Shin Jae Min , Hayuningtyas Ria Aryani , Choi Ji Eun , Shin Jeon-Soo
Published: February 2018

Autophagy is a central intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles, and regulation of autophagy is essential for homeostasis. HMGB1 is an important sepsis mediator when secreted and also functions as an inducer of autophagy by binding to Beclin 1. In this study, we studied the effect of inflachromene (ICM), a novel HMGB1 secretion inhibitor, on autophagy. ICM inhibited autophagy by inhibiting nucleocytoplasmic translocation of HMGB1 and by increasing Beclin 1 ubiquitylation for degradation by enhancing the interaction between Beclin 1 and E3 ubiquitin ligase RNF216. These data suggest that ICM could be used as a potential autophagy suppressor.
Radiation repair models for clinical application
Authors: Dale Roger G
Published: February 2018

A number of newly emerging clinical techniques involve non-conventional patterns of radiation delivery which require an appreciation of the role played by radiation repair phenomena. This review outlines the main models of radiation repair, focussing on those which are of greatest clinical usefulness and which may be incorporated into biologically effective dose assessments. The need to account for the apparent “slowing-down” of repair rates observed in some normal tissues is also examined, along with a comparison of the relative merits of the formulations which can be used to account for such phenomena. Jack Fowler brought valuable insight to the understanding of radiation repair processes and this article includes reference to his important contributions in this area.
Evaluation of Trichoderma spp., Pseudomonas fluorescens and Bacillus subtilis for biological control of Ralstonia wilt of tomato
Authors: Yendyo Shiva , G.C. Ramesh , Pandey Binayak Raj
Published: February 2018

Background:Ralstoniaspp. is a major pathogenic microbe for tomato, which invades the roots of diverse plant hosts and colonizes xylem vessels causing wilt, especially in tropical, subtropical and warm-temperate regions.Ralstoniaspp.produces several virulence factors helping it to invade the plant’s natural defense mechanism. Native isolates ofTrichoderma spp., Pseudomonas fluorescensandBacillus subtiliscan be used as biocontrol agents to control the bacterial wilt and combined application of these beneficial microbes can give better results.

Methods:Bacterial wilt infection in the field was identified by field experts and the infected plant part was used to isolateRalstoniaspp.in CPG media and was positively identified. Subsequently, the efficacy of the biocontrol agents was tested and documented using agar well diffusion technique and digital microscopy. 2ml of the microbial concentrate (109cells/ml) was mixed in one liter of water and was applied in the plant root at the rate of 100 ml per plant as a treatment method.

Results:It was observed that the isolatedTrichodermaspp. AA2 andPseudomonas fluorescensPFS were most potent in inhibiting the growth ofRalstoniaspp.,showing ZOI 20.67 mm and 22.33 mm, respectively. Digital microscopy showed distinct inhibitory effect on the growth and survival ofRalstoniaspp.The results from the field data indicated thatTrichodermaspp. andPseudomonas fluorescensalone were able to prevent 92% and 96% of the infection and combination of both were more effective, preventing 97% of infection. Chemical control methods prevented 94% of infection.Bacillus subtiliscould only prevent 84 % of the infection.  

Conclusions:Antagonistic effect againstRalstonia spp.shown by native isolates ofTrichodermaspp. andP. fluorescensmanifested the promising potential as biocontrol agents. Combined application gave better results. Results shown byBacillus subtiliswere not significant.
World TB Day 2018: The Challenge of Drug Resistant Tuberculosis
Authors: Gupta-Wright Ankur , Tomlinson Gillian S , Rangaka Molebogeng X , Fletcher Helen A
Published: February 2018

On 24th March, the world commemorates the day in 1882 when Dr Robert Koch announced his discovery of Mycobacterium tuberculosis (MTB). Over 130 years later, tuberculosis (TB) continues to affect individuals, communities, and entire health systems and economies. Koch unsuccessfully tried to ‘cure’ TB, and despite major advances in other areas of medicine, control of TB remains elusive- in 2016 TB was the leading infectious cause of death. The STOP TB partnership and World Health Organization (WHO) have announced their theme for World TB Day 2018 “Wanted: Leaders for a TB-Free World. You can make history. End TB.” This theme recognizes that TB is much larger than any one person, institute or discipline of research, and provides an opportunity for us to reflect on the major challenges and consider how we, as a scientific community, can work together and take the lead to address the global crisis of drug-resistant TB (DR-TB).
Optimal Revelation of Life-Changing Information
Authors: Schweizer Nikolaus , Szech Nora
Published: February 2018

Information about the future may be instrumentally useful yet scary. For example, many patients shy away from precise genetic tests about their dispositions for severe diseases. They are afraid that a bad test result could render them desperate as a result of anticipatory feelings. We show that partially revealing tests are typically optimal when anticipatory utility interacts with an instrumental need for information. The same result emerges when patients rely on probability weighting. Optimal tests provide only two signals, which renders them easily implementable. While the good signal is typically precise, the bad one remains coarse. This way, patients have a substantial chance to learn that they are free of the genetic risk in question. Yet even if the test outcome is bad, they do not end in a situation without hope.

This paper was accepted by Manel Baucells, decision analysis.
Technology and inclusivity
Authors: Yaldren Jo , Van Loo Matthew
Published: February 2018

In the current Health and Social Care system, the NHS needs to make better use of information and technology, if it is to meet the demands of an ageing population with increasingly expensive treatment requirements. In this month's Technology Pages, Jo Yaldren and Matthew Van Loo explore the issue of inclusivity as it relates to technology-enhanced care and learning. The themes of digital literacy, autonomy, competence and confidence will be considered, and the cultural and organisational context of this wide-scale change will be highlighted.
Spirituality among family caregivers in palliative care: an integrative literature review
Authors: Lalani Nasreen , Duggleby Wendy , Olson Joanne
Published: February 2018

Background:

Family caregivers experience spiritual and existential concerns while caring for their terminally ill family members.

Aim:

To evaluate and synthesise studies on spirituality among family caregivers in palliative care.

Design:

An integrative literature review of peer-reviewed articles published between 2000 and 2016.

Sample:

Participants were family caregivers (parents, spouses, relatives or friends) caring for an adult (age>18 years) family member with a terminal illness in a palliative care setting.

Results:

Data from 26 published research papers were systematically analysed. Five themes were identified regarding spirituality and family caregiving: a close and meaningful connection, spirituality as a way of coping, spiritual needs and expressions among family caregivers, spirituality to transcend fears, and spirituality in family caregivers' decision-making.

Implications for Practice:

Nurses are encouraged to explore the spirituality and spiritual experiences of family caregivers to support their spiritual wellbeing while caring for their terminally ill family members.
THE BEHAVIOUR OF PENICILLIN IN SYNOVIAL CAVITIES
Authors: Jones G. Blundell
Published: February 2018

1. The behaviour of penicillin injected locally into knee joints is investigated and found to be the only satisfactory way of using the drug in joint wounds and infections.

2. Penicillin persists within the joint for forty-eight hours after injection unless the effusion is being actively absorbed.

3. The additional administration of penicillin by intramuscular injection is recommended when other considerations demand it.
PLASMA CELL TUMOURS
Authors: Lumb George , Prossor T. M.
Published: February 2018

1. Fifteen new cases of plasma cell tumour are reported with a review of the literature.

2. Case examples are quoted to show the gradual merging of the different clinical and pathological syndromes into one entity.

3. A comprehensive analysis of the various manifestations of the disease is made.

4. An attempt is made to correlate the widely differing features of the disease-process and a classification is given.

5. It is considered that metastasis plays no part in this condition.

6. The variety of forms of plasma cell tumours are shown as gradations of an essentially similar disease-process, and are not regarded as separate conditions.
THE MANAGEMENT OF ACUTE CIRCULATORY FAILURE IN AN INJURED LIMB
Authors: Griffiths D. Ll.
Published: February 2018

Ischaemia threatening an injured limb gives rise to the syndrome of pain, pallor, paralysis, and pulselessness. It is due to arterial injury by laceration, compression, intra-mural rupture or contusion, or to arterial spasm with or without demonstrable local arterial damage. The differentiation of spasm without local injury from organic obstruction is not possible by clinical methods.

The suggested plan of treatment and of management is:

1. General systemic investigation (blood-pressure, blood-count, coagulation time, etc.).

2. Removal of all external pressure.

3. Resuscitation.

4. Direct attempt to relieve the obstruction by operation.

5. Post-operative care.

The operative procedure recommended is:

1. Manipulative reduction of the fracture if possible.

2. Proximal control of the artery.

3. Arteriography.

4. Exposure of the occluded artery (unless contra-indicated by time factors and by the anatomy of the collateral circulation), liberation and mobilisation of the vessel, repair by suture where such is necessary and possible, and arterectomy only forirreparable local damage.

5. The provision of sympathetic block by injection or by sympathectomy.

The important elements of post-operative care are:

1. To maintain the blood-pressure while cooling the limb and heating the patient.
TRAUMATIC DISLOCATION OF THE HIP JOINT
Authors: Armstrong J. R.
Published: February 2018

1. One hundred patients with dislocation of the hip joint have been reviewed, many having been re-examined at intervals ranging from two to five years after injury.

2. There were forty-six simple dislocations, forty-three dislocations with fracture of the acetabular rim, seven dislocations with fracture of the acetabular floor, and five dislocations with fracture of the femoral head.

3. Complete recovery, as judged by clinical and radiographic examination, was observed in 76 per cent. of simple dislocations, 63 per cent. of dislocations with fracture of the acetabular rim, and 40 per cent. of dislocations with fracture of the femoral head; in no case of dislocation with fracture of the acetabular floor was recovery complete.

4. Only in one case did myositis ossificans develop, and that was the only case treated by "massage and movements" throughout the first ten weeks after injury.

5. Avascular necrosis of the femoral head was recognised in a smaller proportion of patients than had been expected, but since the follow-up review extended only to four years after injury the results, in this respect, are unreliable. The incidence of this complication after injury to the hip joint cannot be assessed unless the follow-up period is at least five to ten years.

6. Early traumatic arthritis developed in 26 per cent. of patientsâin 15 per cent. of simple dislocations, 25 per cent. of dislocations with fracture of the acetabular margin, 60 per cent. of dislocations with fracture of the femoral head, and 100 per cent. of dislocations with fracture of the acetabular floor.

7. When central or posterior dislocations are accompanied by fracture of the acetabular floor, early arthrodesis is the treatment of choice.

8. Displacement of marginal acetabular fragments is usually corrected by manipulative reduction or by traction.

9. Sciatic paralysis in dislocation of the hip joint is nearly always due to damage of the nerve by a displaced acetabular fragment. In such cases, if the fragment is not replaced accurately by manipulation or traction, operative reduction is urgently indicated.
THE INTERVERTEBRAL LIGAMENTS AS A SOURCE OF SEGMENTAL PAIN
Authors: Sinclair D. C. , Feindel W. H. , Weddell G. , Falconer Murray A.
Published: February 2018

1. The work of Kellgren (1939) and Lewis and Kellgren (1939) on the production of segmental pain by stimulation of structures near the mid-line of the back has been reviewed, and! a number of experiments have been carried out with the object of testing the validity of their conclusions.

2. On both anatomical and experimental grounds there is reason to believe that pain produced in this manner does not arise, as was assumed by Lewis and Kellgren, from irritation of the interspinous ligaments, but is rather due to the stimulation of nerve trunks in the vicinity. The views of Kellgren (1941, 1942) on the etiology of pain in certain cases of sciatica, and on the part played by intervertebral ligaments in the production of pain in the back, have been discussed. They have been shown to rest on an inadequate foundation.

3. The importance in investigations of this kind of a detailed anatomical survey has been emphasized.
BENIGN GIANT-CELL SYNOVIOMA AND ITS RELATION TO "XANTHOMA"
Authors: Stewart M. J.
Published: February 2018

Benign giant-cell synovioma, the most frequent example of which is the well-known myeloid tumour of tendon sheaths, is used as a text for the discussion of the true significance of the so-called "xanthoma" cell. These cells are the result of the phagocytosis of cholesterol esters and are of varied histogenesis. Some are undoubtedly of neoplastic origin; most of them are not, being usually histiocytic, fibrocytic, serosal or endothelial. There is no such thing as a specific xanthoma cell.

The term "xanthosis" might well be used to designate this process of infiltration of tissue with cholesterol fat, and the prefix "xantho-" or the adjective "xanthic" in tumour terminology, as for example in "fibro-xantho-sarcoma," "xanthic neurofibroma," and so on.
OPEN WOUNDS OF THE BRACHIAL PLEXUS
Authors: Brooks Donal M.
Published: February 2018

1. In the first 1600 of the series of peripheral nerve injuries treated during the years 1940-45 at the Peripheral Nerve Injuries Unit, Oxford, 52 per cent. were due to penetrating wounds, and 6 per cent. of these involved the brachial plexus.

2. A specific method of grouping and grading recovery is described: Group Iâlesions of the roots and trunk of C.5, 6; Group IIâlesions of the posterior cord; Group IIIâlesions of C.8, T.1, and the medial cord.

3. The recovery of cases in Group I was good, in Group II fair, and in Group III poor.

4. The brachial plexus was explored on twenty-two occasions. Only in four instances was there interruption of continuityâwhich is in striking contrast with the frequency in more distal degenerative nerve lesions in open wounds.

5. There is no evidence to suggest that neurolysis influenced motor or sensory recovery, but on one occasion it relieved persistent pain in the limb. In general the correlation between operative findings and prognosis was not precise.

6. With one exception, no recovery of consequence took place in the small muscles of the hand after a lesion in continuity, although galvanic stimulation to all paralysed muscles had been given regularly.

7. There is evidence to suggest that innervation of the biceps may not always be limited to C.5 and 6 and that in a proportion of cases C.7 may make a substantial contribution.

8. In five cases (12 per cent.) Horner's syndrome was present; the causation is discussed.

9. In every case of damage to a main vessel there was a marked tendency to joint stiffness, particularly in the hand, but on one occasion only was there evidence of ischaemic changes in the muscles and nerves.

10. The good spontaneous recovery which occurred in Groups I and II; the poor recovery in Group III even in cases where there was an apparently favourable lesion in continuity; the rarity with which division of nerves was found at operation; and the discouraging results of repair in three cases; make it necessary to conclude that routine exploration of open wounds of the brachial plexus is neither profitable nor justifiable.
ISCHIO-FEMORAL ARTHRODESIS OF THE HIP IN TUBERCULOSIS
Authors: Kirkaldy-Willis W. H.
Published: February 2018

1. The anatomical and physiological principles underlying the operation of ischio-femoral arthrodesis by an anterior approach are discussed.

2. The technique of the operation is described.
DE QUERVAIN'S DISEASE
Authors: Keon-Cohen Bryan
Published: February 2018

1. In patients who develop de Quervain's disease variations from the standard pattern of tendons at the wrist are the rule rather than the exception.

2. Conservative treatment is of no value.

3. Adequate exposure, allowing full recognition of all anatomical structures in the region, is advisable, but branches of the radial nerve must be treated with respect.

4. The extensor pollicis brevis tendon is normally small and may pass through a separate osteofibrous canal.

5. Though incision only of the stenosing tendon sheaths may be sufficient, thorough excision is more certain and does no harm.
ISCHIO-FEMORAL ARTHRODESIS BY THE POSTERIOR APPROACH
Authors: Cholmeley J. A. , Nangle E. J.
Published: February 2018

1. The indications for ischio-femoral arthrodesis are considered.

2. The technique of operation through an open posterior approach is described.

3. Indications for the modified Trumble operation are given.

4. The results of ischio-femoral arthrodesis in a series of forty-seven patients (mostly suffering from tuberculous hip disease) are presented.

5. The writers consider that ischio-femoral arthrodesis is the operation of choice in tuberculous disease of the hip, especially in children.
TENDER HEEL DUE TO PAGET'S DISEASE
Authors: Murray J. G.
Published: February 2018

1. Two cases of Paget's disease of the calcaneum are reported; in both, the primary complaint was of pain in the heel.

2. In the first case there were no demonstrable lesions elsewhere, but in the second the typical radiographic appearances of Paget's disease were shown in other bones.

3. The literature on the subject is briefly reviewed.
ON THE TENDON OF THE SUBCLAVIUS MUSCLE
Authors: Cave A. J. E. , Brown R. Warwick
Published: February 2018

1. The descriptive anatomy of the tendinous component of the subclavius muscle is amplified.

2. The subclavius tendon comprises a shorter, medial pars libera, continuous with a longer, narrower, more lateral pars paramuscularis. This last may be prolonged further laterally by two or three tendinous fasciculi.

3. Both parts of the subclavius tendon are constant. By tenodesis they provide, on the average, one and a half to two inches of material eminently suitable for employment in the functional replacement of a damaged costo-clavicular ligament.
"AVIATOR'S ASTRAGALUS"
Authors: Coltart W. D.
Published: February 2018

1. Although fractures and dislocations of the talus have been described since 1608 the rarity of the more severe and complicated injuries has meant a dearth of accurate descriptions or classification in the literature.

2. A series of 228 injuries of the talus occurring in members of the Royal Air Force between 1940 and 1943 has been reviewed.

3. A simple but comprehensive classification of injuries of the talus is presented, together with a review of the pathological anatomy, clinical features, and methods of treatment. The importance of distinguishing between fractures and fracture-dislocations, and of watching carefully for displacements of the subtalar joint, is emphasised.

4. The important complicationsâinfection, avascular necrosis and traumatic arthritis of the ankle or subtalar jointâare discussed. Infection may be the result of a compound injury, or may follow sloughing of the skin stretched over a displaced talus. Early reduction is, therefore, of great urgency in closed injuries. Avascular necrosis of the talus occurs in gross injuries when all or most of the soft-tissue attachments to the bone are severed. Revascularisation and regeneration will take place with patient conservative treatment.

5. The mechanism of injury is discussed.

6. The results of excision of the talus are poor. Every effort should be made to preserve the body of the talus, but if its loss is inevitable a useful foot can be regained by deliberate fusion of the tibia to the calcaneum.
INFECTIONS OF THE HAND
Authors: Robins Robert H. C.
Published: February 2018

1. A report is made of 1000 consecutive cases of infection of the hand treated in the hand clinic of the Surgical Department of the Royal Victoria Infirmary, Newcastle-upon-Tyne.

2. Standard lesions are given a standard treatment. The methods of treatment are described and the results are expressed according to the time to healing from first attendance at the clinic. An attempt was made to review those cases in which a disability of any sort was anticipated, and an assessment made with regard to appearance and function.

3. Many patients came to hospital at a late stage when skin necrosis had already occurred, and particular attention is paid to the management of this complication.

4. It is concluded that the principles of conservative surgery applied to the treatment of infected hands give good results.
RETICULUM-CELL SARCOMA OF BONE
Authors: Valls JoseÌ , Muscolo Domingo , Schajowicz Fritz
Published: February 2018

1. Primary reticulum-cell sarcoma of bone arises from the reticulo-histiocytic elements of bone marrow.

2. The authors have studied ten cases of primary reticulum-cell sarcoma of bone, and have compared the clinical, pathological and radiographic features with those of thirty-five cases of Ewing's sarcoma.

3. In their microscopic studies Hortega's staining techniques were used in addition to orthodox methods.

4. There are histological differences between a reticulum-cell sarcoma and Ewing's sarcoma.

5. Certain clinical and radiographic features help the differentiation between the two tumours.

6. The progress and treatment of the reticulum-cell sarcoma are reviewed in detail.
PREPARATION AND USE OF HETEROGENOUS BONE GRAFTS
Authors: Guilleminet M. , Stagnara P. , Perret T. Dubost
Published: February 2018

1. The preparation of heterogenous grafts of calf bone is described.

2. The results of experimental application of such grafts in dogs and guinea pigs are recorded.

3. The results of eighty heterogenous grafts in humans are reported.

4. It is concluded that if the conditions are carefully controlled the results of heterogenous grafting are satisfactory.
DYSPLASIA EPIPHYSIALIS PUNCTATA
Authors: Frank W. W. , Denny M. B.
Published: February 2018

Radiological and histological examinations are described in a full term stillborn infant with punctate epiphysial dysplasia diagnosed in utero as achondroplasia.
CHEMOTHERAPY OF TUBERCULOSIS OF BONES AND JOINTS
Authors: Wilkinson M. C.
Published: February 2018

Streptomycin and iso-nicotinic acid hydrazide are two powerful drugs lethal to tubercle bacilli, when access to the infected tissues is free. For early disease, before ischaemia and necrosis become established, they are curative: afterwards they are not. In this paper the use of surgery to augment their action has been discussed. The development of such methods may well revolutionise the treatment of skeletal tuberculosis. Therein lies a danger because attempts to cure the patient by exterminating the tubercle bacilli in his lesion may lead to a precarious recovery: treatment directed against the bacilli may greatly facilitate a real cure if constitutional treatment is also applied to make the patient immune. Revolutionary though the change may become, it will not be so great as the revolution which occurred thirty years ago when open-air hospitals were first provided for patients with skeletal tuberculosis. The first patient ever seen on a surgical ward by the author, when he was a student, suffices still as an example. A child with tuberculosis of the cervical spine was admitted from out-patients with multiple discharging sinuses from the neck which was supported in a sodden plaster jacket. "Whoever," said the house surgeon dramatically, "removes that plaster, will kill that child." Most unfortunately his words were true. Many other such patients could, in those days, be seen in the wards of city hospitals. It was largely due to the work of Sir Robert Jones, friend of children, that the value of constitutional treatment became recognised. With the combination of the old knowledge and the development of the new, a new chapter in the treatment of skeletal tuberculosis has opened and rapid restoration of function and permanent cure can now take the place of long and sometimes crippling illness.
THE EVOLUTION OF LATERAL RHACHOTOMY
Authors: Capener Norman
Published: February 2018

It is clear that in lateral rhachotomy we have a procedure which is appropriate for approach to the vertebral bodies in a variety of pathological processes including, besides the relief of Pott's paraplegia, the treatment of non-paraplegic tuberculosis, the exploration of spinal tumours, the relief of certain types of traumatic paraplegia and the drainage of suppurative osteitis of the vertebral bodies. For tuberculous disease we find in lateral rhachotomy a technical procedure which provides a meeting point for the solution of several ideas. These are the evacuation of tuberculous abscesses as enunciated by Pott and developed by MeÌnard, the revascularisation of avascular areas, the removal of necrotic material and the direct removal of the features causing spinal cord compression. It is to the latter only that I think I have made a small contribution. For all other purposes, between lateral rhachotomy and the classical costo-transversectomy, the differences if any are extremely small. The fact remains that the direct surgical approach to lesions of the vertebral bodies has a wide scope of usefulness.
PERIPHERAL ARTERIAL DISEASE
Authors: Stammers F. A. R.
Published: February 2018

1. The history of the development of the operation of sympathetic ganglionectomy for vasospasm is related.

2. A simple classification is given of the common diseases of the peripheral arteries.

3. The symptoms of peripheral arterial disease are described.

4. The investigations are discussed.

5. The treatment, both conservative and surgical, is discussed, with comments on arterial grafts.

6. Special points are made regarding poliomyelitis, acrocyanosis, Bazin's disease, cervical rib, vascular injuries and crutch arteritis.

7. The long-term results of sympathectomy are reviewed.
THE ANATOMY OF HALLUX VALGUS
Authors: Haines R. Wheeler , McDougall A.
Published: February 2018

1. The anatomy of the forefoot in hallux valgus is compared with the normal, with a review of the literature and descriptions of anatomical preparations, observations at operation and radiographs.

2. The early and essential lesions are stretching of the ligaments on the medial side of the metatarso-phalangeal joint that attach the medial sesamoid and basal phalanx to the metatarsal, and erosion of the ridge that separates the grooves for the sesamoids on the metatarsal head.

3. In established hallux valgus a sagittal groove, formed where the cartilage is free from pressure by either the phalanx or the ligaments, cuts off a medial eminence, which articulates with the stretched ligaments, from a restricted area for the phalanx.

4. Apart from osteophytic lipping which squares off the outline of the eminence as it is seen in radiographs and a small amount of lipping of the ridge on the metatarsal there is no evidence of new bone growth. In chronic cases the eminence may degenerate or disappear.

5. The articular surfaces at the cuneo-metatarsal joint become adapted to the changed positions of the metatarsal without gross pathological change.

6. The four deep transverse ligaments that bind together the five plantar pads of the metatarso-phalangeal joints are not unduly stretched, so that as the metatarsals spread it is the ligaments that bind the pads to the heads of the metatarsals that give way.

7. The plantar metatarsal artery to the first space pursues a tortuous course between the two heads of the flexor hallucis brevis. In hallux valgus the course becomes still more tortuous and part of the pain experienced may be due to ischaemic effects.
THE USE OF THE ACRYLIC HEAD PROSTHESIS IN HIGH FRACTURES OF THE FEMORAL NECK
Authors: Cregan J. C. F.
Published: February 2018

1. Sixty-five cases of medial fracture of the femoral neck treated by substitution of the head by an acrylic prosthesis have been studied.

2. In general, the long-term clinical results of prosthetic arthroplasty after fresh fractures have been disappointing. The method has given slightly better results in the treatment of old fractures.

3. In view of the almost perfect results obtained after successful Smith-Petersen nailing in the presence of an adequate blood supply to the femoral head, it seems unjustifiable to abandon this principle for immediate substitution with an acrylic femoral head. Nevertheless it is believed that an arthroplasty of this type is justified in fractures seen late, and in fresh subcapital fractures when the fracture is irreducible. If a prosthesis is to be used, more protection for the stump of the neck against the strain of weight bearing is essential; a simple head prosthesis is inadequate, and a head with either a neck extension or an intramedullary prolongation may give better results.
LOCALISED OSTEOCHONDRITIS OF THE LUMBAR SPINE
Authors: Lamb Douglas W.
Published: February 2018

1. Seven cases of localised lumbar spine defects in children associated with low back pain are described.

2. The importance is emphasised of the recognition and differentiation of the condition from tuberculosis, which it may resemble both clinically and radiographically.
INVESTIGATION OF THE GROWTH AND STRUCTURE OF THE TIBIA OF THE RABBIT BY MICRORADIOGRAPHIC AND AUTORADIOGRAPHIC TECHNIQUES
Authors: Owen Maureen , Jowsey Jenifer , Vaughan Janet
Published: February 2018

1. The detailed anatomy and calcification of the upper half of the tibia in rabbits varying in age from six weeks to twelve months has been studied.

2. The structure of the bone varies at different levels, but a section taken from the same level in the tibia from animals of the same age presents a reasonably constant picture.

3. It has been shown that this variation in structure at different levels is directly related to a difference between the axis of growth and the bone axis. This difference is a result of the unique shape of the tibia.

4. Autoradiographic studies confirm the localised concentration of radioactive strontium in areas of active bone formation where uptake is rapid.

5. The long retention of radioactive strontium in the skeleton (that is, the slow turnover) is a result of the slowness of resorption of bone (endosteal, periosteal or Haversian) in the cortex. Not only is the process slow but it is extremely localised.

6. The significance of these anatomical and physiological characteristics in relation to radiation injury is discussed.
TRAUMATIC ANEURYSM OF THE PERONEAL ARTERY
Authors: Scott J. H. S.
Published: February 2018

A case of traumatic aneurysm of the peroneal artery at the level of its perforating branch is described. The intimate and variable relationship of this vessel to the flexor hallucis longus muscle and the tethering effect of its perforating branch predispose to its damage in operations through the postero-lateral approach to the region of the ankle.
VOLKMANN'S CONTRACTURE: TREATMENT BY EXCISION OF THE INFARCT
Authors: Seddon H. J.
Published: February 2018

1 . In the common type of Volkmann's ischaemic contracture affecting the forearm flexors, the infarct takes the form of an ellipsoid with its axis in the line of the anterior interosseous artery and with its central point a little above the middle of the forearm. The greatest damage is at the centre and usually falls most heavily on flexor digitorum profundus and flexor pollicis longus, which are often necrotic. Those muscles more superficially placed, and sometimes the deep extensors, are more likely to exhibit fibrosis.

2. The median nerve runs near the centre of the ellipsoid and may exhibit profound ischaemia. The ulnar nerve, lying at the edge of the ischaemic zone, tends to be less severely affected.

3. The treatment for this condition is excision of all tissues irreparably damaged by ischaemia. If this operation is performed within twelve months from the time of injury, correction of the contracture should be almost complete. The tendons of shortened but active muscles are lengthened or transplanted.

4. After such excision it is possible to carry out reconstructive procedures commonly used in the surgery of lower motor neurone disorders and of trauma. A wide variety of tendon transplantations is available. The median nerve may be repaired either by a free graft or, in cases where both nerves have been extensively damaged by ischaemia, by an ulnar to median nerve-pedicle graft.
THE ANTERIOR TIBIAL SYNDROME
Authors: Mayor G. E.
Published: February 2018

1. A case of persistent exercise ischaemia affecting the anterior tibial group of muscles is described.

2. Pathogenesis and treatment are discussed. Decompression of the anterior tibial compartment is required if the patient is unwilling to give up whatever activity causes the exercise pain.
MYELOGRAPHY IN THE LUMBAR REGION WITH WATER-SOLUBLE CONTRAST MEDIUM
Authors: Annakliniek Th. Boesman
Published: February 2018

The follow-up of these seventy-three cases suggested the following conclusions:

1. The clinical signs alone are not always sufficient to make the diagnosis of herniated nucleus pulposus with sufficient accuracy.

2. When positive, myelography was reliable as a means of localising the hernia.

3. In doubtful cases in which conservative treatment failed a clearly positive myelography turned the scale for a well-indicated operation.

4. In doubtful cases a clearly negative myelography has often rightly been a contra-indication for laminectomy.

5. No serious complication from the use of water-soluble contrast medium for myelography has been encountered.
THE MECHANICAL BASIS OF BONE FORMATION
Authors: Scott J. H.
Published: February 2018

1. Bones consist essentially of bundles of collagenous fibres united by a cementing substance in which the inorganic material lies in the form of minute plate-like crystals.

2. During weight bearing and muscle action bones as a whole are deformed to a variable extent. Periods of deformation are followed by periods of relaxed pressure during which the bones tend to return to their normal form.

3. These variations in deformation and elastic recoil set up alternating pressures and tensions within the bones along the bone cyrstal encrusted fibres which make up the trabeculae, lamellae and Haversian systems, and these alternating phases of compression and tension stimulate the activity of osteoblasts so that bone formation predominates over bone resorption.

4. These alterations of pressure and tension are intermittent and reciprocal in nature and do not, as postulated by the trajectorial theory, involve different trabeculae, nor is it necessary to consider whether tension or pressure is the more important phase in determining bone deposition.

5. The pressure exerted by cysts, tumours, erupting teeth, etc., is of a quite different nature, as is the response to trauma or callus formation in the healing of fractures. These processes are essentially vascular phenomena involving localised areas of bony tissue and not bones as mechanical units.
LONGITUDINAL OSTEOTOMY OF THE TIBIA
Authors: Nicholson O. R.
Published: February 2018

1. "Reed" osteotomy has proved a satisfactory method for the correction of torsional deformity of the tibia and of associated minor varus or valgus deformity.

2. It is an "osteotomy in continuity" and maintains stability of the bone.

3. The position of the limb may be adjusted at the first change of plaster.

4. Three cases of non-union occurred in thirty-eight operations.

5. The operation should not be done on adults. Perhaps it may be wise to reserve it for even younger patients because its success depends on the pliability of cortical bone, which rapidly diminishes with increasing age.
ROTATION MOVEMENTS OF THE SPINE WITH SPECIAL REFERENCE TO SCOLIOSIS
Authors: Roaf Robert
Published: February 2018

The principle of Occam's razor proves nothing. Nevertheless, it is possible to explain all the phenomena of severe scoliosis on the basis of a primary rotation deformity alone. The typical rotation type of scoliotic deformity can be reproduced artificially by fitting vertebrae together in an abnormal rotatory relationship without any element of lateral flexion. From this, certain mechanical factors inevitably come into play which must tend to increase the deformity. Above all, the forces responsible for progressive scoliosis are dynamic and active, not just passive. The spine readily compensates for a passive, non-progressive deformity such as a simple wedge vertebra. It is my belief that rotation is usually the dominant factor and that correction and control of severe scoliosis can only be achieved by concentrating on the rotation deformity. I am well aware that this is an old idea but its essential truth has been insufficiently appreciated in recent years and we have not faced its full implications. Failure to correct rotation invites recurrence. Conversely, even a slight reduction in rotation usually produces a marked cosmetic improvement, often out of all proportion to the radiographic appearances.
TWO CASES OF OBSTETRICAL SEPARATION (EPIPHYSIOLYSIS) OF THE UPPER FEMORAL EPIPHYSIS
Authors: Michail J. P. , Theodorou S. , Houliaras K. , Siatis N.
Published: February 2018

1. Two new cases of obstetrical separation of the upper femoral epiphysis are described.

2. Diagnosis in the first instance must be largely clinical, because radiological confirmation of the injury may be delayed.

3. The simple method of longitudinal traction is the treatment recommended.

4. It is notable that in our first case the ossification centre of the femoral head appeared at the exceptionally early age of fifteen days.
HYPERPARATHYROIDISM DUE TO PARATHYROID CARCINOMA
Authors: Cook P. B.
Published: February 2018

A case of hyperparathyroidism from carcinoma of the parathyroid gland which recurred locally and metastasised to the lung is described. There was a history of renal lithiasis and peptic ulceration. Improvement followed initial surgical removal but the tumour recurred and death resulted from hyperparathyroidism.