Cytogenetic studies on the in-vitro genotoxicity of 4-nitroquinoline-1-oxide on human-lymphocytes

Using the UV-mimetic mutagen 4-nitroquinoline-1-oxide (4NQO) to induce genetic damage in human cells (lymphoblastoid lines and primary cultures of peripheral blood samples), chromosome aberrations were induced by treating the cells with 4NQO at 1 X 10(-5) M for 24 h. The overwhelming majority of chromosome aberrations was of the chromatid (S + G2) type instead of the chromosome (G1) type. The most common chromatid aberrations were simple breaks, isochromatid breaks, and chromatid exchanges. When the number of chromatid breaks per cell value was used as a measurement for 4NQO sensitivity, lymphoblastoid cells from a xeroderma pigmentosum patient showed the highest sensitivity, followed by the cells of two melanoma patients and normal persons. These preliminary results suggest that 4NQO may be employed to develop an assay system as a biomarker for determining UV sensitivity in the human population.     

Racial differences in aortic atheroma in patients undergoing transesophageal echocardiography for unexplained stroke or transient ischemic attack

Racial differences in the prevalence of complex thoracic aortic atheroma were evaluated in 318 patients referred for transesophageal echocardiography after unexplained stroke or transient ischemic attack. African-Americans were found to have fewer complex thoracic aortic atheroma and fewer combined cardiac sources of embolus than Caucasian patients. This finding persists after adjusting for racial differences in atherosclerotic risk factors.     

Factor VIII Clotting Antigen (VIIICAg) in Haemophilia Measured by Two Immunoradiometric Assays (IRMA) using Different Antibodies, and the Measurement of Inhibitors to Procoagulant Factor VIII (VIIIC) by IRMA

Factor VIII clotting antigen (VIIICAg) was measured by immunoradiometric assay (IRMA) using two different antibodies. Both antibodies arose in polytransfused severe haemophiliacs and had similar titres against VIIIC. In 12 normal plasmas there was no significant difference in VIIICAg values obtained (VIIICAg (AbI) = VIIICAg (AbII)). In the majority of 15 severe haemophiliacs tested VIIICAg was undetectable by both antibodies. In 28 mild to moderate haemophiliacs VIIICAg (AbII) was significantly greater than VIIICAg (AbI) ( P < 0·01) suggesting different antigenic determinants. The difference, however, was small and does not affect diagnosis of haemophilia. A modified IRMA has been used to measure and VIIIC inhibitors by competition of the inhibitor with ¹²⁵I labelled VIIICAg antibodies for common antigenic determinants. Using an inhibitor of 225 Bethesda units as a standard, results by IRMA of inhibitors in severe haemophiliacs have been similar to those obtained by clotting assay, but with a sensitivity of 0·01 u/ml suggesting the possible use in the detection of weak inhibitors.     

Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma

Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.     

PEG hydrogel degradation and the role of the surrounding tissue environment

Poly(ethylene glycol) (PEG)‐based hydrogels are extensively used in a variety of biomedical applications, due to ease of synthesis and tissue‐like properties. Recently there have been varied reports regarding PEG hydrogel's degradation kinetics and in vivo host response. In particular, these studies suggest that the surrounding tissue environment could play a critical role in defining the inflammatory response and degradation kinetics of PEG implants. In the present study we demonstrated a potential mechanism of PEG hydrogel degradation, and in addition we show potential evidence of the role of the surrounding tissue environment on producing variable inflammatory responses. Copyright © 2013 John Wiley & Sons, Ltd.     

The Value of Magnetoencephalography to Guide Electrode Implantation in Epilepsy

To investigate if Magnetoencephalography (MEG) can add non-redundant information to guide implantation sites for intracranial recordings (IR). The contribution of MEG to intracranial recording planning was evaluated in 12 consecutive patients assessed pre-surgically with MEG followed by IR. Primary outcome measures were the identification of focal seizure onset in IR and favorable surgical outcome. Outcome measures were compared to those of 12 patients matched for implantation type in whom non-invasive pre-surgical assessment suggested clear hypotheses for implantation (non-MEG group). In the MEG group, non-invasive assessment without MEG was inconclusive, and MEG was then used to further help identify implantation sites. In all MEG patients, at least one virtual MEG electrode generated suitable hypotheses for the location of implantations. No differences in outcome measures were found between non-MEG and MEG groups. Although the MEG group included more complex patients, it showed similar percentage of successful implantations as the non-MEG group. This suggests that MEG can contribute to identify implantation sites where standard methods failed.     

Metformin therapy in patients with chronic kidney disease

Metformin therapy is limited in patients with chronic kidney disease (CKD) due to the potential risk of lactic acidosis. This open‐label observational study investigated metformin and lactate concentrations in patients with CKD (n = 22; creatinine clearances 15–40 ml/min) and in two dialysed patients. Patients were prescribed a range of metformin doses (250–2000 mg daily) and metformin concentrations were compared with data from healthy subjects (scaled to 1500 mg twice daily). A subset of patients (n = 7) was controlled on low doses of metformin (250 or 500 mg daily). No correlation between metformin and lactate concentrations was observed. Three patients had high lactate concentrations (>2.7 mmol/l) and two had high metformin concentrations (3–5 mg/l), but none had any symptoms of lactic acidosis. Reducing metformin dosage and monitoring metformin concentrations will allow the safe use of metformin in CKD, provided that renal function is stable.