Management of back pain in patients with previous back surgery

The 80,000 or so patients a year who continue to have chronic, disabling back pain after one or more spinal surgeries are said to have failed back surgery syndrome. There are no controlled studies to guide physicians in the management of these patients. Six anatomical abnormalities of the spine most commonly result in back surgery, and 7 undesirable outcomes lead to failed back surgery syndrome. On the basis of 5 large retrospective studies and our clinical experience, we suggest a systematic approach to these patients. This approach is focused on determination of the specific anatomical abnormality responsible for ongoing symptoms, an abnormality that may or may not be related to the initial abnormality for which surgery was performed. One or more of 5 nonsurgical treatment options may be useful to prevent the need for further surgery, as each subsequent surgery has a lower likelihood of success.     

Utility of 4-(5,5-dimethyl-3-oxo-cyclohex-1-enylamino)benzenesulfonamide in the synthesis of novel quinolines as possible anticancer and radioprotective agents

The present work reports the possible utility of 4-(5,5-dimethyl-3-oxo-cyclohex-1-enylamino)benzenesulfonamide in the synthesis of some novel 4-(quinolin-1-yl) benzenesulfonamide derivatives (6a-o). Structures of the newly synthesized compounds were confirmed by elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Compounds 6k, 6j and 6m showed interesting cytotoxic activity compared with doxorubicin (CAS 23214-922-8) as a reference drug. Additionally, compound 6c exhibited in vivo radioprotective activity, against gamma-irradiation, in mice.     

Measurement and removal of adherent endotoxin from titanium particles and implant surfaces.

Aseptic loosening is thought to be due primarily to osteolysis induced by cytokines and prostaglandins that are produced in response to implant-derived wear particles. Because endotoxin has many of the same effects as have been reported for wear particles, we hypothesized that adherent endotoxin may be responsible for the biological responses induced by wear particles. We demonstrated the presence of significant levels of adherent endotoxin on commonly used preparations of titanium particles as well as on titanium and titanium-alloy implant surfaces. In contrast, supernatants obtained by centrifugation of particle suspensions contained approximately 1% as much endotoxin as did the particles. Therefore, it is erroneous to assume that particles do not contain endotoxin on the basis of data that it cannot be detected in their supernatants or filtrates. These results emphasize the importance of considering the potential role of adherent endotoxin when examining the in vitro effects of wear particles and the in vivo performance of orthopaedic implants. We also developed a protocol that removed more than 99.94% of the adherent endotoxin from the titanium particles without detectably affecting their size or shape. The removal of adherent endotoxin will allow comparison of the biological responses induced by particles with or without adherent endotoxin.     

Synthesis and antimicrobial evaluation of some new cyclooctanones and cyclooctane-based heterocycles

The versatile synthon (E)-2-((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane-based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2-((p-sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes.     

HER2/neu Expression: A Predictor for Differentiation and Survival in Children With Wilms Tumor

Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expression could be implicated in the development of many tumors. The clinico-demographic and pathological data of 28 Wilms tumor patients were , reviewed. The tissue samples were examined by light Microscopy then immunohistochemical staining for HER2/neu expression. Additional 28 normal surrounding renal tissue specimens were included. There was significant differences between HER2/neu positive and HER2/neu negative Wilms tumors in relation to stage, histological phase and epithelial differentiation (P > 0.05 for all). The overall survival advantage was noticed if Wilms tumor was at early stages (I and II) (Log-rank = 13.23 and P > 0.001), homologous epithelial differentiation (Log-rank = 6.01 and P = 0.04), as well as HER2/neu positive tumors (Log-rank = 6.14 and P = 0.013). A statistical significant trend toward a longer recurrence free survival was, noticed if Wilms tumor was at early stages (Log-rank = 21.22, P > 0.0000) and if HER2/neu positive (Log-rank = 8.53, P = 0.004). HER2/neu expression in Wilms tumor could be a marker for epithelial and homologous differentiation and its expression could be a good predictor for overall survival and longer recurrence free survival.     

FCY-302, a Novel Small Molecule,Induces Apoptosis in Leukemia and Myeloma Cells by Attenuating Key Antioxidant and Mitochondrial Enzymes

Arylidene analogs are well proven for biological activities. FCY-302, a novel small molecule belonging to this class, was screened for its biological efficacy in leukemia and myeloma cells. FCY-302 selectively inhibited proliferation of cancer cells with GI50 values of 395.2 nM, 514.6 Nm, and 642.4 nM in HL-60, Jurkat, and RPMI-8226 cells, respectively. The compound also increased sub-G0 peak in the cancer cell cycle and favored apoptosis determined by annexin V assay. The compound decreased the antiapoptotic Bcl-2 levels and increased proapoptotic Bax proteins in leukemia and myeloma cell lines. FCY-302 attenuated the mitochondrial membrane-bound Na⁺ /K⁺ ATPase, Ca²⁺ ATPase, and Mg²⁺ ATPase enzyme activities and significantly decreased activities of antioxidant enzymes like SOD, CAT, G_R, and GST in all the three cancer cells tested. Our findings suggest that FCY-302 inhibits the proliferation of leukemia and myeloma cancer cells by altering key mitochondrial and antioxidant enzymes, eventually driving them to apoptosis. These results drive focus on FCY-302 and its analogs to be developed as potential small molecules with bioactivities against cancer.     

Can spermatozoa be retrieved in non‐obstructive azoospermic patients with high FSH level?: A retrospective cohort study

We aimed in this retrospective study to evaluate non‐surgical preoperative parameters and testicular histopathology in determining the sperm retrieval rate (SRR) in non‐obstructive azoospermic (NOA) patients. We evaluated the data of 1,395 consecutive patients who underwent 1st time micro‐dissection testicular sperm extraction (micro‐TESE) that was done by fifteen different senior andrologists and a consequent undefined number of biologists assisting them in the operative rooms from January 2010 to May 2013 in a specialised IVF centre. Our study did not demonstrate any statistical significance between the mean age, the mean duration of infertility and finally, the mean of FSH levels of the patients with positive and negative micro‐TESE outcomes (p‐value 0.391, 0.543, 0.767 respectively). Moreover, our study did not demonstrate any association between different types of hormonal therapy prior to micro‐TESE and patients with positive micro‐TESE outcome (p‐value 0.219). Interestingly, our study showed positive associations between the testicular histopathology SCO (sertoli cell only syndrome) and high FSH and sperm retrieval rate (p < 0.001, 0.02 respectively). Logistic regression analysis revealed high statistical significance between sperm retrieval rate and high FSH level and testicular histopathology (OR 1.6, 0.21, 95% CI lower 1.2, 0.008 and upper 2.1, 0.06 and finally p 0.003, <0.001 respectively). This study reveals that preoperative testicular biopsy is unnecessary to predict the sperm retrieval rate in NOA patients.