A Commentary on the Need for 3D-Biologically Relevant In Vitro Environments to Investigate Astrocytes and Their Role in Central Nervous System Inflammation.

Astrocytes execute essential functions in the healthy CNS, whilst also being implicated as a limitation to functional regeneration and repair after injury. They respond to injury to minimize damage to healthy tissue whilst also attempting to seal the broken blood-brain-barrier, however, they impede recovery if they are persistent and form a permanent scar in the injured brain. As such, it is of great importance to understand the mechanism underlying the astrocytic response to injury, and this understanding is currently limited by the in vitro environments available to scientists. Biomaterials such as nanofibres and hydrogels offer great potential for the development of superior, 3D cell culture environments in which to study astrocyte behavior and phenotype. The implementation of such in vitro environments with a particularly interdisciplinary approach can improve the field's understanding of astrocytes, their role in central nervous system inflammation, and elucidate potential strategies to achieve functional regeneration.

Using WHO-FRAX to describe fracture risk: experience in primary care.

Ideally those at highest risk of fracture should be identified prior to fracture occurrence to reduce mortality, morbidity and costs. Case-finding strategies for those at high risk of first fracture or systematic case-finding strategies following fracture are recommended in the UK, rather than population-based screening to identify individuals at high fracture risk. General practices in the UK hold relevant data on individuals beyond fracture history that could allow identification of a wider group of patients at highest risk of fracture. The aim of the paper is to evaluate the feasibility of applying the WHO-FRAX fracture risk calculator to general practice populations using existing recorded data. A cross-sectional study of 2467 women aged 50 years and older (mean 66.2 years, standard deviation = 11.3) registered with two Scottish General Practices with low deprivation (one semi-rural, one urban) was undertaken. Patient data were extracted from the two general practices' patient information databases and the WHO-FRAX calculator was applied to these data. WHO-FRAX calculation was possible on 1872 patients. Of these, 687 patients were found to have a high fracture risk (risk of major facture ≥15% and or risk of hip fracture ≥3% - 37% of the WHO-FRAX assessed cohort) and should be considered for follow-up. In conclusion, use of the WHO-FRAX calculator using general practice-held data is feasible and can help to identify a patient group at higher fracture risk. Further evaluation and treatments can then be targeted at this group.

68Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: correlation with final histopathology.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology. METHODS: We conducted a chart review from February 2015 to January 2017 of 50 male patients staged for prostate cancer using PSMA PET/CT and mpMRI who then underwent radical prostatectomy. Pre-operative PSMA PET/CT and mpMRI were paired with corresponding histopathology. Correlations, sensitivity, and specificity were used for comparisons. RESULTS: A total of 81 lesions were confirmed by histopathology. Fifty index lesions were detected by histopathology, all of which were detected by PSMA PET/CT (100% detection), and 47 by mpMRI (94% detection). Thirty-one histologically confirmed secondary lesions were detected, 29 of which were detected by PSMA PET/CT (93.5% detection), and 16 by mpMRI (51.6% detection). PSMA had better sensitivity for index lesion localization than mpMRI (81.1 vs. 64.8%). Specificity was similar for PSMA PET/CT and mpMRI (84.6 vs. 82.7%). SUVmax of index lesions ranged from 2.9 to 39.6 (M = 9.27 ± 6.41). Index lesion SUVmax was positively correlated with PSA (rho = 0.48, p < 0.001) and ISUP grade (rho = 0.51, p < 0.001). CONCLUSIONS: PSMA-PET/CT provided superior detection of prostate cancer lesions with better sensitivity than mpMRI. PSMA-PET/CT can be used to enhance locoregional mpMRI to provide improved detection and characterization of lesions.

Acute changes in urine protein excretion may predict chronic ifosfamide nephrotoxicity: a preliminary observation.

PURPOSE: To evaluate proteinuria occurring early after ifosfamide therapy and to assess the use of changes in proteinuria in the prediction of severe chronic nephrotoxicity. METHODS: One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to characterize urine protein excretion in 12 children with solid tumours before and after the first course of ifosfamide treatment, and in 24 healthy children. Chronic nephrotoxicity was evaluated at 6 months after ifosfamide treatment and graded as none, mild, moderate or severe. RESULTS: Urine from healthy children and from 10 of 12 patients before ifosfamide therapy showed a protein band with a molecular weight (95.4 kDa) corresponding to that of Tamm-Horsfall protein but no lower molecular weight proteins. After the first course of ifosfamide this 95.4-kDa protein was lost in six of ten patients with a concomitant appearance of a low molecular weight proteinuria (< 70 kDa) in eight. Tamm-Horsfall protein was lost in two of five patients who subsequently developed no or mild nephrotoxicity and in four of five patients who subsequently developed moderate or severe nephrotoxicity. CONCLUSIONS: Early subclinical changes in urine protein excretion after ifosfamide, manifested by a loss of Tamm-Horsfall protein excretion, may be predictive of subsequent chronic nephrotoxicity.

Hemorrhagic lymphadenopathy as a presenting feature of primary al amyloidosis.

Lymphadenopathy associated with hemorrhage as a presenting feature of primary (AL) amyloidosis has not previously been described. We report two such cases one of whom had an acquired factor X and IX deficiency. The clinical presentations were characterized by sudden spontaneous enlargement of lymph nodes followed by partial regression. In both cases significant delay in diagnosis, and hence treatment, occurred due to the mode of presentation. One patient died with rapidly progressive disease but the other has had an excellent response to therapy with high-dose melphalan (HDM, 200 mg/m2) and peripheral blood stem cell rescue. AL amyloid should be considered in all patients presenting with hemorrhagic lymphadenopathy.

Rectangular game theory and metabolic response to random changes in environmental states.

Rectangular game theory is applied to the response of organisms to random environmental changes: A hypothetical example of the response of a facultative algae to random changes in illumination is analyzed. Two strategies are discussed: Bayes' risk and maximin. It is shown how to detect such strategies in populations. The analysis does not require assumptions about the form of the relationship between metabolic activities and selective advantage, but assumptions about evolutionary optimization are required. The maximin strategy is shown to be related to metabolic homeostasis.

Cervical chordoma presenting as retropharyngeal mass and dysphonia: Case report and literature review.

Chordoma is a rare primary bone tumour that presents with signs and symptoms of local compression and myelopathy. A case of C4 chordoma with unusual clinical and imaging features is presented. The diagnosis of chordoma requires clinical, radiological and pathological correlation. Clinical features may include laryngeal symptoms arising from distortion of local anatomy. Characteristic tumour appearance and distribution on imaging plays a key role in diagnosis and management of this slow growing tumour with potential for major surgical morbidity.

Chordoma: radiological-pathological correlation.

This review correlates the imaging findings and histological appearances seen in chordomas in a series of patients presenting at our institution, together with a published literature review. A parallel presentation of photographs of imaging findings and microscopic histological findings is made, with the aim being to enhance recognition of this uncommon but clinically significant entity.

An assessment of the clinical use of glyceryl trinitrate in a hospital outpatient population.

Despite the availability of information on the use of glyceryl trinitrate (GTN) in standard texts, in practice many patients fail to obtain maximum benefit from GTN. This study of an Outpatient population, documents the patients' knowledge of the use and precautions which should apply to GTN and records the ways in which these patients took the drug. Fifty patients who regularly took GTN (greater than 5 tablets per week) were asked a series of questions by the same interviewer. Forty-nine of the 50 patients took GTN for the relief of chest pain, but only 34 patients knew that the drug could be used to prevent chest pain. Although 48 patients kept their bulk supply of GTN in the original container, over 40% transferred some or all of the tablets to other containers and locations. Seventy per cent of patients knew that GTN tablets deteriorate with time. However, knowledge of the factors which influence the rate of deterioration was lacking. Less than half the patients knew that the prompt relief of pain or the local effects on the buccal mucosa could be used as simple tests of the activity of tablets. It is recommended that all physicians should take more time to explain to their patients how to use glyceryl trinitrate correctly.

Stimulation of photophosphorylation and cytochrome c photooxidation by pteridines.

A number of pteridines were examined for activity in promoting photophosphorylation in broken spinach chloroplasts and in stimulating cytochrome c photooxidation in sonicated chloroplasts. Correlation was found between activities for the 2 reactions. Photophosphorylation promoted by pteridines was inhibited by DCMU and by anaerobic conditions. It is concluded that pteridines may stimulate photophosphorylation by linking photosystem 1 with molecular oxygen and thereby allowing noncyclic electron flow. Aromatic pteridines in both the 2,4-dihidroxy- and 2-amino-4-hydroxy-series were active; substitution at the 6 (or 7) position was a necessary but not sufficient condition for activity in both reactions. Reducing agents increased photophosphorylation activity of aromatic pteridines and an oxidant increased activity of a tetrahydropteridine. It is postulated that pteridines are most active in their semiquinone or unstable dihydro forms.

The relationship between bcl-2 expression and response to chemotherapy in acute leukaemia.

Immunocytochemistry was used to assess bcl-2 expression in blasts obtained from the bone marrow of 28 patients with acute lymphoblastic leukaemia (ALL) (16 children and six adults at presentation and three children and three adults on relapse) and 20 with acute myeloid leukaemia (AML) (19 adults and one child, 13 with de novo AML, 11 at presentation and two on relapse, and seven secondary to myelodysplasia or chronic myeloid leukaemia). Slides were examined both for the percentage of positive cells and for the intensity of staining using a five-point scale. There was a statistically significant increase in both the percentage of positive cells seen (P < 0.002) and the intensity of staining (P < 0.01) between samples obtained at relapse and those at presentation in ALL. There was a significantly greater intensity of staining in cells from patients with ALL (P < 0.05) and AML (P < 0.05) who failed to achieve remission after chemotherapy than in those who responded. The intensity of staining in cases of secondary AML was lower than that in de novo disease (P < 0.01). These results suggest that expression of bcl-2 may be an important prognostic feature in both de novo AML and in ALL, but not in secondary AML.

Successful high dose therapy for relapsed mediastinal large B cell lymphoma following surgical repair of anterior chest wall defect.

We describe a man with relapsed large B cell mediastinal lymphoma and associated infected large anterior chest wall defect who required high dose salvage therapy for his underlying disease. An initial mediastinotomy wound, associated with recurrent sepsis, had developed into an abscess, then fistula and eventually a large anterior chest wall defect. Safe use of salvage chemotherapy required reconstructive surgery consisting of a pedicled muscle flap. The subsequent high dose chemotherapy was carried out without complications and 15 months later the patient is alive and well.