US and MRI of pediatric ocular masses with histopathological correlation

We review our experience with unusual ocular pathologies, some mimicking retinoblastoma, that were referred to our institution during the past two decades. After presenting the imaging anatomy of the normal eye, we discuss pertinent clinical and pathological features, and illustrate the US and MRI appearance of retinoblastoma, medulloepithelioma, uveal melanoma, persistent fetal vasculature, Coats disease, corneal dermoid, retinal dysplasia and toxocara granuloma. Features useful in discriminating among these entities are emphasized.     

Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices via multiple receptor pathways

BACKGROUND AND PURPOSE

Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute slices.

EXPERIMENTAL APPROACH

The effect of CBD on synaptic transmission was examined in rat hippocampal cultures and acute slices using whole cell patch clamp and standard extracellular recordings respectively.

KEY RESULTS

Cannabidiol decreased synaptic activity in hippocampal cultures in a concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD in culture were significantly reduced in the presence of the cannabinoid receptor (CB₁) inverse agonist, {"type":"entrez-nucleotide","attrs":{"text":"LY320135","term_id":"1257555575","term_text":"LY320135"}}LY320135 but were unaffected by the 5-HT_1A receptor antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic transmission, an effect that was abolished by the proposed CB₁ receptor antagonist, AM251, in addition to {"type":"entrez-nucleotide","attrs":{"text":"LY320135","term_id":"1257555575","term_text":"LY320135"}}LY320135 and WAY100135.

CONCLUSIONS AND IMPLICATIONS

Cannabidiol reduces synaptic transmission in hippocampal in vitro preparations and we propose a role for both 5-HT_1A and CB₁ receptors in these CBD-mediated effects. These data offer some mechanistic insights into the effects of CBD and emphasize that further investigations into the actions of CBD in the CNS are required in order to elucidate the full therapeutic potential of CBD.     

Right adolescent idiopathic thoracic curve (Lenke 1 A and B): does cost of instrumentation and implant density improve radiographic and cosmetic parameters?

In adolescent idiopathic scoliosis (AIS) there has been a shift towards increasing the number of implants and pedicle screws, which has not been proven to improve cosmetic correction. To evaluate if increasing cost of instrumentation correlates with cosmetic correction using clinical photographs. 58 Lenke 1A and B cases from a multicenter AIS database with at least 3 months follow-up of clinical photographs were used for analysis. Cosmetic parameters on PA and forward bending photographs included angular measurements of trunk shift, shoulder balance, rib hump, and ratio measurements of waist line asymmetry. Pre-op and follow-up X-rays were measured for coronal and sagittal deformity parameters. Cost density was calculated by dividing the total cost of instrumentation by the number of vertebrae being fused. Linear regression and spearman’s correlation were used to correlate cost density to X-ray and photo outcomes. Three independent observers verified radiographic and cosmetic parameters for inter/interobserver variability analysis. Average pre-op Cobb angle and instrumented correction were 54° (SD 12.5) and 59% (SD 25) respectively. The average number of vertebrae fused was 10 (SD 1.9). The total cost of spinal instrumentation ranged from $6,769 to $21,274 (Mean $12,662, SD $3,858). There was a weak positive and statistically significant correlation between Cobb angle correction and cost density (r = 0.33, p = 0.01), and no correlation between Cobb angle correction of the uninstrumented lumbar spine and cost density (r = 0.15, p = 0.26). There was no significant correlation between all sagittal X-ray measurements or any of the photo parameters and cost density. There was good to excellent inter/intraobserver variability of all photographic parameters based on the intraclass correlation coefficient (ICC 0.74–0.98). Our method used to measure cosmesis had good to excellent inter/intraobserver variability, and may be an effective tool to objectively assess cosmesis from photographs. Since increasing cost density only improves mildly the Cobb angle correction of the main thoracic curve and not the correction of the uninstrumented spine or any of the cosmetic parameters, one should consider the cost of increasing implant density in Lenke 1A and B curves. In the area of rationalization of health care expenses, this study demonstrates that increasing the number of implants does not improve any relevant cosmetic or radiographic outcomes.     

PARP inhibition in atherosclerosis and its effects on dendritic cells,T cells and auto-antibody levels

Objective

Atherosclerosis is a chronic inflammatory process. Poly(ADP-ribose) polymerase-1 (PARP), a nuclear enzyme linked to DNA repair, has been shown to be involved in atherogenesis; however, the effects on dendritic cells, T cells and serum auto-antibody levels are not fully understood.

Methods

Male Apoe^-/- mice on a western diet were treated with the PARP inhibitor 1NO-1001 (n = 15), while the control group (n = 15) received 5% glucose solution for 10 weeks.

Results

Inhibition of PARP markedly reduced atherosclerotic lesion development (p = 0.001). Immunohistochemistry and mRNA analysis revealed a reduced inflammatory compound inside the lesion. Focusing on dendritic cells, INO-1001 reduced number of cells (p = 0.04), grade of activation, represented by I/12 (p = 0.04) and Cd83 (p = 0.03), and grade of attraction, represented by Mip3α (p = 0.02) in the plaque. Furthermore, INO-1001 decreased number of T lymphocyte (p = 0.003) in the lesion and grade of activation after stimulation with oxLDL in vitro. Moreover, serum IgM antibody levels to oxLDL were significantly lower in INO-1001 treated mice (p = 0.03).

Conclusions

Functional blockade of PARP by INO-1001 reduces atherosclerotic lesion development. The anti-atherogenic effect is beside already known mechanisms also moderated due to modulation of DC and T cell invasion and activation, DC attraction as well as IgM antibody levels to oxLDL.     

Gene copy number variation and common human disease

Fanciulli M, Petretto E, Aitman TJ. Gene copy number variation and common human disease. Variation in gene copy number is increasingly recognized as a common, heritable source of inter‐individual differences in genomic sequence. The role of copy number variation is well established in the pathogenesis of rare genomic disorders. More recently, germline and somatic copy number variation have been shown to be important pathogenic factors in a range of common diseases, including infectious, autoimmune and neuropsychiatric diseases and cancer. In this review, we describe the range of methods available for measuring copy number variants (CNVs) in individuals and populations, including the limitations of presently available assays, and highlight some key examples of common diseases in which CNVs have been shown clearly to have a pathogenic role. Although there has been major progress in this field in the last 5 years, understanding the full contribution of CNVs to the genetic basis of common diseases will require further studies, with more accurate CNV assays and larger cohorts than have presently been completed.     

Antimycobacterial Evaluation of Fifteen Medicinal Plants in South Africa

Fifteen plant species were collected from the Nelspruit Botanical Garden based on a list of plants provided by Phytomedicine Programme at the University of Pretoria and their ethnopharmacological information. Hexane, dichloromethane (DCM), acetone and methanolic extracts were screened for antimycobacterial activity against Mycobacterium smegmatis. The acetone extract of Milletia stulhimannii was the most active, showing activity against Mycobacterium smegmatis with minimum inhibitory concentration (MIC) value of 0.13 mg/ml. Acetone extracts for all plants had lower MIC values ranging between 0.11–1.25 mg/ml against M. smegmatis. Milletia stulhimannii, Albizia gummifera, Xanthocercis zambesiaca and Barringtonia racemosa have shown great potential as anti-tuberculosis agents. They were active against M. smegmatis with average MIC values of acetone extracts of 0.13 mg/ml.     

Fibroblast growth factor (FGF) and FGF receptor-mediated autocrine signaling in non-small-cell lung cancer cells

Despite widespread expression of epidermal growth factor (EGF) receptors (EGFRs) and EGF family ligands in non-small-cell lung cancer (NSCLC), EGFR-specific tyrosine kinase inhibitors (TKIs) such as gefitinib exhibit limited activity in this cancer. We propose that autocrine growth signaling pathways distinct from EGFR are active in NSCLC cells. To this end, gene expression profiling revealed frequent coexpression of specific fibroblast growth factors (FGFs) and FGF receptors (FGFRs) in NSCLC cell lines. It is noteworthy that FGF2 and FGF9 as well as FGFR1 IIIc and/or FGFR2 IIIc mRNA and protein are frequently coexpressed in NSCLC cell lines, especially those that are insensitive to gefitinib. Specific silencing of FGF2 reduced anchorage-independent growth of two independent NSCLC cell lines that secrete FGF2 and coexpress FGFR1 IIIc and/or FGFR2 IIIc. Moreover, a TKI [(+/-)-1-(anti-3-hydroxy-cyclopentyl)-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido-[4,5-d]pyrimidin-2-one (RO4383596)] that targets FGFRs inhibited basal FRS2 and extracellular signal-regulated kinase phosphorylation, two measures of FGFR activity, as well as proliferation and anchorage-independent growth of NSCLC cell lines that coexpress FGF2 or FGF9 and FGFRs. By contrast, RO4383596 influenced neither signal transduction nor growth of NSCLC cell lines lacking FGF2, FGF9, FGFR1, or FGFR2 expression. Thus, FGF2, FGF9 and their respective high-affinity FGFRs comprise a growth factor autocrine loop that is active in a subset of gefitinib-insensitive NSCLC cell lines.     

Monosegmental fixation for the treatment of fractures of the thoracolumbar spine

Background:

A short vertebral arthrodesis has been one of the objectives of the surgical treatment of fractures of the thoracolumbar spine. We present here clinical, functional and radiographic outcome obtained after monosegmental fixation (single posterior or combined anterior and posterior) of specific types of unstable thoracolumbar fractures.

Materials and Methods:

Twenty four patients with fractures of the thoracolumbar spine submitted to monosegmental surgical treatment (Group I - 18 single posterior monosegmental fixations and Group II - 6 combined anterior and posterior fixations) were retrospectively evaluated according to clinical, radiographic and functional parameters. The indication for surgery was instability or neurological deficit. All the procedures were indicated and performed by the senior surgeon (Helton LA Defino).

Results:

The patients from group I were followed-up from 2 to 12 years (mean: 6.65±2.96). The clinical, functional and radiographic results show that a single posterior monosegmental fixation is adequate and a satisfactory procedure to be used in specific types of thoracolumbar spine fractures, The patients from group II were followed-up from 9 to 15 years (mean: 13 ± 2,09 years). On group II the results of clinical evaluation showed moderate indices of residual pain and of satisfaction with the final result. The values obtained by functional evaluation showed that 66.6% of the patients were unable to return to their previous job and presented a moderate disability index (Oswestry = 16.6) and a significant reduction of quality of life based on the SF-36 questionnaire. Radiographic evaluation showed increased kyphosis of the fixed vertebral segment during the late postoperative period, accompanied by a reduction of the height of the intervertebral disk.

Conclusion:

It is possible to stabilize the fractures which have an anterior good load-bearing capacity by a standalone posterior monosegmental fixation. However this procedure, even with an anterior support is not suitable for fracture involving the vertebral body.