Implantation metastasis of primary malignant rhabdoid tumor of the brain in an adult (one case report)

Primary malignant rhabdoid tumor (PMRT) of the brain is a rare and recently described neoplasm of youth. We report magnetic resonance imaging (MRI), computed tomography (CT), and pathology of one case of PMRT in an adult which seeded along the needle track for stereotactic biopsy. Med. Pediatr. Oncol. 28:223–227 © 1997 Wiley-Liss, Inc.     

Endodontic complications in teeth with vital pulps restored with composite resins: a systematic review

Composite resin is used extensively for restoration of teeth with vital pulps. Although cell culture studies have disclosed harmful effects on pulpal cells, any untoward clinical effects, manifest as adverse pulpal responses, have yet to be determined. This study comprises a systematic review, designed to address the question of whether the risk of endodontic complications is greater with composite resin restorations than with other restorative materials, such as amalgam. The study methodology involved (i) formulation of the research question, (ii) construction and conduct of an extensive literature search with (iii) interpretation and assessment of the retrieved literature. A search of the medical database PubMed was complemented with a search of the Controlled Trials Register (CENTRAL). The initial search yielded 1043 publications, the abstracts of which were read independently by the authors. After additional searches, 10 studies were included in the review. In all the included studies, the level of evidence was assessed as low. No conclusions could therefore be drawn. The included studies reported few, if any, endodontic complications. Little or no differences emerged between teeth restored with composite resins and those restored with amalgam. To determine whether composite resin restorations of teeth with vital pulps are associated with an increased risk for development of endodontic complications such as apical periodontitis, further evidence is needed, from well‐constructed studies with a large number of participants.     

Metastasis-associated MCL1 and P16 copy number alterations dictate resistance to vemurafenib in a BRAFV600E patient-derived papillary thyroid carcinoma preclinical model

BRAF^V600E mutation exerts an essential oncogenic function in many tumors, including papillary thyroid carcinoma (PTC). Although BRAF^V600E inhibitors are available, lack of response has been frequently observed. To study the mechanism underlying intrinsic resistance to the mutant BRAF^V600E selective inhibitor vemurafenib, we established short-term primary cell cultures of human metastatic/recurrent BRAF^V600E-PTC, intrathyroidal BRAF^V600E-PTC, and normal thyroid (NT). We also generated an early intervention model of human BRAF^V600E-PTC orthotopic mouse. We find that metastatic BRAF^V600E-PTC cells elicit paracrine-signaling which trigger migration of pericytes, blood endothelial cells and lymphatic endothelial cells as compared to BRAF^WT-PTC cells, and show a higher rate of invasion. We further show that vemurafenib therapy significantly suppresses these aberrant functions in non-metastatic BRAF^V600E-PTC cells but lesser in metastatic BRAF^V600E-PTC cells as compared to vehicle treatment. These results concur with similar folds of down-regulation of tumor microenvironment–associated pro-metastatic molecules, with no effects in BRAF^WT-PTC and NT cells. Our early intervention preclinical trial shows that vemurafenib delays tumor growth in the orthotopic BRAF^WT/V600E-PTC mice. Importantly, we identify high copy number gain of MCL1 (chromosome 1q) and loss of CDKN2A (P16, chromosome 9p) in metastatic BRAF^V600E-PTC cells which are associated with resistance to vemurafenib treatment. Critically, we demonstrate that combined vemurafenib therapy with BCL2/MCL1 inhibitor increases metastatic BRAF^V600E-PTC cell death and ameliorates response to vemurafenib treatment as compared to single agent treatment. In conclusion, short-term PTC and NT cultures offer a predictive model for evaluating therapeutic response in patients with PTC. Our PTC pre-clinical model suggests that combined targeted therapy might be an important therapeutic strategy for metastatic and refractory BRAF^V600E-positive PTC.     

Prenatal TCDD in mice increases adult autoimmunity

Two immunologically different mouse strains, C57BL/6 and SNF₁, were exposed to a mid-gestation dose of TCDD. The C57BL/6 mouse has a high-affinity aryl hydrocarbon receptor (AhR) and is sensitive to TCDD. The SNF₁ mouse has a low-affinity AhR but spontaneously develops autoimmune nephritis. Autoreactive Vβ⁺CD4⁺17a and Vβ⁺CD3⁺ T cells were increased at 24-weeks-of-age in offspring of C57BL/6 mice, more so in females than males. The cytokine IFN-γ was elevated in the females, while IL-10 was elevated in males. Phenotypic changes in B-lineage cells were present in bone marrow and spleen, and circulating autoantibodies were increased after prenatal TCDD. Kidneys of males showed significant anti-IgG and anti-C3 deposition, suggesting early-stage autoimmune disease. The SNF₁ offspring similarly showed increased peripheral Vβ⁺ cells in the females, increased autoantibody production in both sexes, and increased IFN-γ production in females. Male SNF₁ mice had increased anti-IgG and anti-C3 deposition in kidneys. Both mouse models therefore showed clear signatures of enhanced autoimmunity after prenatal TCDD.     

Breast feeding may protect children against Campylobacter jejuni associated diarrhoea

To investigate the bacterial etiology of infant diarrhea in Karachi, Pakistan, 180 rectal swab samples collected from diarrhea patients under 5 years of age and 30 samples from age- and sex-matched healthy children were analyzed. Enteropathogenic organisms were isolated from 70 case samples (38.9%). The two most common etiologic agents were Campylobacter jejuni (19.4%) and Aeromonas hydrophilia (6.1%). Salmonella, Shigella, and Yersina appear to have a limited incidence in this age group. None of the control specimens yielded any enteropathogen. Breast-fed infants had a significantly lower risk of enteric infection. A pathogen was isolated in 26.0% of samples from breast-fed children with diarrhea compared with 46.8% of samples from bottle-fed diarrhea patients. All C jejuni infections identified in this study involved bottle-fed children. Boiled water was used to prepare infant formula in only 31.1% of these patients. These findings are consistent with those of other studies showing a decreased rate or severity of diarrhea in breast-fed infants. Mothers should be encouraged to breast feed their infants or, if this is not possible, to use boiled water for the preparation of infant formula.     

Comparison of topical gatifloxacin 0.3% and ciprofloxacin 0.3% for the treatment of bacterial keratitis

PURPOSE: To compare the bacteriologic and clinical efficacy of gatifloxacin and ciprofloxacin for the treatment of bacterial keratitis. DESIGN: Prospective, randomized clinical trial. METHODS: A total of 104 eyes of 104 patients with bacterial keratitis seen at a tertiary eye-care center were randomized to treatment with gatifloxacin 0.3% eyedrops (GAT group, 50 eyes) or ciprofloxacin 0.3% eyedrops (CIP group, 54 eyes). Patients and the treating physician were masked to the antibiotic being used. Main outcome measure studied was healing of the ulcer. Patients lost to follow-up before complete healing were excluded from further analysis. RESULTS: A significantly higher proportion of ulcers in the GAT group exhibited complete healing compared with those in the CIP group (39 eyes [95.1%] vs 38 [80.9%]; P=.042). Gatifloxacin demonstrated a significantly better action than ciprofloxacin against gram-positive cocci in vitro (P<.001), and the percentage of ulcers caused by these pathogens that healed in the GAT group was significantly better than in the CIP group (P=.009). Mean time taken for healing of ulcer and the efficacy against gram-negative bacteria did not significantly differ between the two groups. CONCLUSIONS: Gatifloxacin had a significantly better action against gram-positive cocci both in vitro and in vivo when compared with ciprofloxacin. In view of these organisms being the leading cause of keratitis worldwide, gatifloxacin may be a preferred alternative to ciprofloxacin as the first-line monotherapy in bacterial keratitis.     

Novel homozygous loss-of-function mutations in RP1 and RP1L1 genes in retinitis pigmentosa patients

ABSTRACT

Background: Retinitis pigmentosa (RP) is a heterogeneous group of ocular dystrophy. It is challenging to identify the underlying genetic defect in individuals with RP due to huge genetic heterogeneity. This study was designed to delineate the genetic defect(s) underlying RP in extended Saudi families and to describe the possible disease mechanism.

Materials and Methods: Fundus photography and a high definition optical coherence tomography (HD-OCT) were performed in order to detect the earlier stages of macular degeneration. Genomic DNA was extracted followed by genome-wide SNP genotyping and whole exome sequencing (WES). Exome data was filtered to identify the genetic variant(s) of interest.

Results: Clinical examination showed that affected individuals manifest key features of RP. The fundus exam shows pale optic disc and bone spicules at the periphery. OCT shows macular degeneration as early as at the age of 4 years. Whole genome scan by SNPs identified multiple homozygous regions. WES identified a 10 bps novel insertion mutation (c.3544_3545insAGAAAAGCTG; p.Ala1182fs) in the RP1 gene in both affected individuals of family A. Affected individual from family B showed a large insertion of 48 nucleotides in the coding part of the RP1L1 gene (c.3955_3956insGGACTAAAGTAATAGAAGGGCTGCAAGAAGAGAGGGTGCAGTTAGAGG; p.Ala1319fs). Sanger sequencing validates the autosomal recessive inheritance of the mutations.

Conclusion: The results strongly suggest that the insertion mutations in the RP1 and RP1L1 genes are responsible for the retinal phenotype in affected individuals from two families. Heterozygous individuals are asymptomatic carriers. We propose that the protective allele in other homozygous regions in heterozygous carriers contribute to the phenotypic variability in asymptomatic individuals.     

Synthesis of novel quinoxalinone derivatives by conventional and microwave methods and assessing their biological activity

In this study, twenty-one arylaminoquinoxalinone derivatives were synthesized and their antibacterial activities against Staphylococci aureus, Pseudomonas aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Shigella pneumoniae were evaluated relative to known antibiotics; augmentin, ampicillin, and chloramphenicol. The insecticidal activities of the prepared compounds were also investigated against Tribolium castaneum using permethrin as a standard insecticide. The derivatives were synthesized using both conventional and microwave techniques. Their structures were confirmed using spectral techniques and elemental analysis.