Sliding window dual gradient echo (SW-dGRE): T1 and proton resonance frequency (PRF) calibration for temperature imaging in polyacrylamide gel

The aim of the work is to evaluate a magnetic resonance imaging (MRI) thermometry sequence suitable for targeting of focused ultrasound (FUS) when used in vascular occlusion studies. A sliding window dual gradient echo (SW-dGRE) sequence was used. This sequence has the capability of monitoring both T1 relaxation and phase changes, which vary with temperature. Preliminary work involved quantification of the changes in T1 relaxation time with temperature and obtaining the PRF shift coefficient in polyacrylamide gel as it underwent an exothermic reaction during polymerization (avoiding the use of an external heat source). Temperature changes were visualized using thermal maps acquired with the sequence. For FUS guidance a thermal imaging technique is required with a temporal resolution <5 s, a spatial resolution of approximately 1 mm and a temperature resolution of approximately 5 degrees C. The sequence was optimized to improve the CNR (contrast to noise ratio) and SNR (signal to noise ratio) in the phase and magnitude images respectively. The PRF coefficient obtained for the polyacrylamide gel was -9.98 +/- 0.24 ppb degrees C(-1), whilst deltaT1 and temperature change were related by a proportionality factor, the T1 temperature coefficient, of 102.3 +/- 2.9 ms degrees C(-1). The sequence produces an image at every 1.4 s interval. In both magnitude and phase data, the in-plane resolution is +/- 1.2 mm and the temperature resolution is approximately 2 degrees C. The advantage of this sequence is that the temperature obtained from the magnitude data can be confirmed independently using the phase data and vice versa. Thus the sequence can essentially be crosschecked.     

Ecstasy use among college undergraduates: gender,race and sexual identity

We examined a random sample (N=3606) of undergraduates at one large midwestern university and explored correlates of ecstasy use and how use varied by gender, race, and sexual identity. Approximately 10% of the sample used ecstasy in their lifetime; 7% had used within the past year and 3% within the past month. Ecstasy was the second most likely illicit drug to be used, marijuana being the first. Multivariate logistic regression indicated that while men and women were equally likely to have used ecstasy, excessive partying, sexual identity, and grade point average were strongly correlated with ecstasy use. After adjusting for several factors, the number of sexual partners increased the likelihood of ecstasy use, as did self-reported sexual identity; gay, lesbian, and bisexual students were more than two times as likely to have used ecstasy in the past year. Significant relationships existed between ecstasy use and other substance use such as binge drinking, marijuana use, and cigarette smoking. Implications for interventions are discussed.     

Mechanisms of toxicity of 2- and 5-hydroxy-1,4-naphthoquinone; absence of a role for redox cycling in the toxicity of 2-hydroxy-1,4-naphthoquinone to isolated hepatocytes

The mechanisms of toxicity to isolated rat hepatocytes of two structurally related naphthoquinones have been studied. Both 5-OH-1,4-naphthoquinone (5-OH-1,4-NQ; juglone) and 2-OH-1,4-naphthoquinone (2-OH-1,4-NQ; lawsone) caused a concentration-dependent cytotoxicity to hepatocytes which was preceded by a depletion of intracellular glutathione. 5-OH-1,4-NQ caused a depletion of intracellular glutathione when incubated either at 4 degrees C or 37 degrees C whereas 2-OH-1,4-NQ caused a depletion of intracellular glutathione when the hepatocytes were incubated at 37 degrees C but not at 4 degrees C. 5-OH-1,4-NQ but not 2-OH-1,4-NQ reacted with glutathione in buffered solution. These results suggested that the depletion of intracellular glutathione by 2-OH-1,4-NQ is enzyme mediated whereas in the case of 5-OH-1,4-NQ the direct chemical reaction with gluathione may be largely responsible for the depletion. A critical role for depletion of protein thiols in menadione-induced cytotoxicity has been proposed. In agreement with earlier work, menadione caused a decrease in protein sulphydryls prior to cell death, however, at cytotoxic concentrations of both 2-OH-1,4-NQ and 5-OH-1,4-NQ this decrease only accompanied rather than preceeded cell death. The mechanism of toxicity of 5-OH-1,4-NQ is similar to that of other naphthoquinones and involves formation of its corresponding naphthosemiquinone, active oxygen species and redox cycling as it stimulated a disproportionate increase in both microsomal NADPH oxidation and oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phase I Study of Nintedanib Incorporating Dynamic Contrast‐Enhanced Magnetic Resonance Imaging in Patients With Advanced Solid Tumors

Background.

This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors.

Methods.

Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.d. The primary endpoint was maximum tolerated dose (MTD). DCE-MRI studies were performed at baseline and on days 2 and 28.

Results.

Fifty-one patients received nintedanib 100–450 mg once daily (n = 40) or 250 mg b.i.d. (n = 11). Asymptomatic reversible liver enzyme elevations (grade 3) were dose limiting in 2 of 5 patients at 450 mg once daily. At 250 mg b.i.d., 2 of 11 patients experienced dose-limiting toxicity (grade 3 liver enzyme elevation and gastrointestinal symptoms). Common toxicities included fatigue, diarrhea, nausea, vomiting, and abdominal pain (mainly grade ≤2). Among 45 patients, 22 (49%) achieved stable disease; 7 remained on treatment for >6 months. DCE-MRI of target lesions revealed effects in some patients at 200 and ≥400 mg once daily.

Conclusion.

Nintedanib is well tolerated by patients with advanced solid malignancies, with MTD defined as 250 mg b.i.d., and can induce changes in DCE-MRI. Disease stabilization >6 months was observed in 7 of 51 patients.     

Treatment of patello-femoral arthritis using the Lubinus patello-femoral arthroplasty: a retrospective review

There are few published results in the literature on patello-femoral arthroplasty. The aim of this study was to help to define the place of patello-femoral arthroplasty in the treatment of isolated patello-femoral arthritis. All patients who underwent patello-femoral arthroplasty using the Lubinus prosthesis for patello-femoral arthritis between 1992 and 1998 in two neighbouring district general hospitals were studied. There were 34 patients who underwent 45 arthroplasties. The modified Hungerford and Kenna scoring system and the Insall and Crosby scoring system were used to clinically evaluate the patients. Serial radiographs were assessed for patellar malalignment, mechanical failure and progressive arthritic change. Twenty-three knees (64%) had a good or excellent result, six (17%) had an unsatisfactory result and seven (19%) were revised to either a total knee arthroplasty (5 knees) or patellofemoral arthroplasty (2 knees). Although the results do not compare favourably with those of total knee replacement for generalised arthritis of the knee; we believe that with careful patient selection coupled with careful surgical technique, patello-femoral arthroplasty can be successfully used to treat isolated patello-femoral osteoarthritis.