Regional myocardial oxygen tension: 19F MRI of sequestered perfluorocarbon

A novel noninvasive method of measuring local myocardial oxygen tension (pO₂) In the perfused rat heart using ¹⁹F MRI is demonstrated. Tissue pO₂ was determined on the basis of the ¹⁹F spin-lattice relaxation rate (R1) of perflubron (perfluorooctyl bromide) sequestered in the heart after IV infusion of an emulsion. Spectroscopic measurement of R1 was previously used to measure a global weighted average of oxygen status. ¹⁹F MRI now provides 3D spatial resolution indicating local cardiac pO₂ under normally perfused, globally ischemic, and regionally ischemic conditions.     

Specific and innervation-regulated expression of the intermediate filament protein nestin at neuromuscular and myotendinous junctions in skeletal muscle

The intermediate filament proteins nestin, vimentin, and desmin show a specific temporal expression pattern during the development of myofibers from myogenic precursor cells. Nestin and vimentin are actively expressed during early developmental stages to be later down-regulated, vimentin completely and nestin to minimal levels, whereas desmin expression begins later and is maintained in mature myofibers, in which desmin participates in maintaining structural integrity. In this study we have analyzed the expression levels and distribution pattern of nestin in intact and denervated muscle in rat and in human. Nestin immunoreactivity was specifically and focally localized in the sarcoplasm underneath neuromuscular junctions (NMJs) and in the vicinity of the myotendinous junctions (MTJs), ie, in regions associated with acetylcholine receptors (AChRs). This association prompted us to analyze nestin in neurogenically and myogenically denervated muscle. Immunoblot analysis disclosed a marked overall increase of accumulated nestin protein. Similar to the extrajunctional redistribution of AChRs in denervated myofibers, nestin immunoreactivity extended widely beyond the NMJ region. Re-innervation caused complete reversion of these changes. Our study demonstrates that the expression levels and distribution pattern of nestin are regulated by innervation, ie, signal transduction into myofibers.     

Salvage radiotherapy following biochemical relapse after radical prostatectomy: proceedings of the Genito-Urinary Radiation Oncologists of Canada consensus meeting

For patients with recurrent prostate cancer after radical prostatectomy, salvage radiotherapy is the only potentially curative treatment option. However, until recently there has been a paucity of data on the effectiveness of this approach. In light of recently published studies, the Genito-Urinary Radiation Oncologists of Canada (GUROC) met and crafted a consensus statement regarding the current place of salvage radiotherapy. GUROC also identified gaps in current knowledge and identified ongoing study protocols that will advance our knowledge in this area.This report summarizes the main conclusions of the meeting and the commentary provided during the consensus-building process, and outlines the consensus statement that was subsequently adopted.     

High-intensity focused ultrasound for prostate cancer: a systematic review

High-intensity focused ultrasound (HIFU) has recently been promoted as a non-invasive treatment option for prostate cancer. This systematic review sought to evaluate the evidence comparing it with standard treatment in patients with localised prostate cancer. The literature review included searches of MEDLINE, EMBASE, the Cochrane Library, annual meetings’ abstracts and websites of evidence-based practice guideline producers. Studies were included if they were randomised controlled trials comparing HIFU with current management approaches, or were meta-analyses, systematic reviews or practice guidelines addressing HIFU. No randomised controlled trials or meta-analyses were identified. Seven systematic reviews and two practice guidelines were identified; neither contained randomised controlled trials. Adjusting the selection criteria to include case series found 34 clinical studies of HIFU. Twenty-nine evaluated HIFU as the primary treatment and five examined HIFU as salvage treatment for recurrence after radiotherapy. In most studies the outcomes used to determine efficacy were negative biopsy rates or prostate-specific antigen (PSA) levels. Among the 29 studies of HIFU as the primary treatment, negative biopsy rates ranged from 35 to 95% in 21 studies, a PSA nadir of ≤0.5 ng/ml ranged from 55 to 91% in 10 studies and mean PSA nadirs ranged from 0 to 1.9 ng/ml in 17 studies. Five studies reported 5-year disease-free survival rates ranging from 55 to 95%. Among five studies of HIFU as salvage treatment, negative biopsy rates ranged from 73 to 84% in four studies, a PSA nadir of ≤0.5 ng/ml ranged from 57 to 66% in three studies and mean PSA nadirs were 1.97 and 2.38 ng/ml in two studies, respectively. Current evidence on HIFU use in prostate cancer patients is of low quality, rendering it difficult to draw conclusions about its efficacy. Until results from case series are confirmed in prospective studies, the widespread use of HIFU is not supported.     

In vivo oxygen tension and temperature: Simultaneous determination using 19F NMR spectroscopy of perfluorocarbon

A novel technique is presented to measure in vivo simulataneously oxygen tension and temperature using ¹⁹F NMR spectroscopy of perfluorocarbon. This work examines the variation with oxygen tension (pO₂) and temperature of the individual spin lattice relaxation rates (R₁) of the ¹⁹F resonances of the perfluorocarbon emulsion Oxypherol-ET. A linear relationship between R₁ and pO₂ is confirmed for all the resonances at any specific temperature in the range 27–50°C. Similarly, a linear relationship is determined between R₁ and temperature at any specific pO₂ in this temperature range. Each resonance behaves uniquely with respect to temperature and pO₂ and consideration of 2 or more resonances uniquely defines pO₂ and temperature simultaneously, and unambiguously. This concept is demonstrated in vivo in a murine tumor and perfused rat heart, where pO₂ and temperature were both determined without prior knowledge.     

Magnetic Resonance Imaging and Magnetization Transfer in Experimental Myonecrosis in the Rat

Experimental myonecrosi–induced by injection of notexin into rat tibialis anterior muscle–and subsequent regeneration were studied from 1 h to 20 days postinjury with magnetic resonance imaging using conventional and magnetization transfer sequences, and these findings were correlated with histopathology. MR images revealed necrosis within 1 h postinjection. Histopathologically, necrotized fibers enlarged and intercellular spaces widened, indicating intracellular and extracellular edema, which began to decrease after 48 h, whereafter the formation of new myofibers predominated. T₂ increased progressively until 7.5 h, while T₁ increased until 24 h. Magnetization transfer contrast (MTC) and magnetization transfer rate (R_wm) decreased rapidly postinjection; the decrease in R_wm lasted longer than in MTC (96 h versus 48 h, respectively). Spin echo, inversion recovery and magnetization transfer sequences revealed the lesions equally effectively. MR images and relaxation parameters reflect well the extent of histopathological injury and edema in the acute phase, whereas specific tissue changes in the regenerative phase were not detectable by MRI. MT imaging and especially magnetization transfer rate are as sensitive as conventional T2 contrast to alterations in water imbalance.     

GU radiation oncologists consensus on bone loss from androgen deprivation

The majority of GU radiation oncologists in Canada attended a consensus meeting in November 2004. The topic of osteoporosis in men receiving androgen deprivation therapy (ADT) for prostate cancer was identified as a key theme. A chaired session with keynote speakers and review of the evidence took place followed by open debate. Participants were provided with background information. Osteoporosis was defined as a T-score < or = -2.5, but the importance of risk factors and clinical findings is noted. Dual DEXA is the current standard for assessment of bone density and relates well to fracture risk. The lifetime risk of fracture is 13% for men over the age of 50 years even without the influence of ADT. Lifestyle, dietary and supplementation advice are provided both to prevent and to manage osteoporosis. The role for prophylactic bisphosphonate therapy in men on ADT without osteoporosis has not been established. Follow-up DEXA scans are required to monitor density, risk and response to interventions. Fracture incidence and BMD should be considered in the trial design of studies involving prolonged ADT. Osteoporosis is a treatable condition and the oncologist should employ ADT with this knowledge. A follow-up e-mail survey was carried out regarding the consensus statement. Responses were received from 49 of the 69 attendees (71%), and overall there was an 89% agreement with the consensus statement. This is now adopted as national practice guidelines for radiation oncologists employed prolonged ADT in prostate cancer patients.