Plasma atropine concentrations associated with decreased intestinal motility in horses

IntroductionAtropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. Materials and methodsEight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plasma were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal motility was measured using borborygmi frequency and electrointestinography (EIG). Experimental data were analyzed using a non-linear mixed effects model. The model was then used to simulate different dosing regimens. ResultsAtropine significantly decreased borborygmi response and EIG response. Six horses developed clinical signs of abdominal pain. The pharmacokinetic typical values were 0.31, 1.38, 0.69, and 1.95 L/kg center dot h for the volumes of the central, the highly perfused, the scarcely perfused compartments, and the total body clearance, respectively. The pharmacodynamic typical values were 0.31 mu g/L and 0.6 and 207 nV(2)7 cpm for the plasma concentration at 50% of the maximum response and the maximum response and the baseline of cecal EIG response, respectively. Six different dosing regimens of topical atropine sulfate to the eye (0.4 and 1 mg every hour, every 3 h, and every 6 h) were simulated. ConclusionThe IV PK/PD data coupled with simulations predict that administration of 1 mg of topical atropine sulfate administered to the eye every hour or every 3 h will lead to atropine accumulation in plasma and decreased intestinal myoelectric activity. Administration every 6 h predicted a safe dosing regimen in full-sized horses. Clinical studies would be valuable to confirm the conclusions. For smaller equids and horses put at risk for colic due to othercauses, droplet bottles that deliver 40 mu l of 1% atropine sulfate per drop or less may be used to lower the risk further

Relation between pain and skeletal metastasis in patients with prostate or breast cancer.

The aim of this study was to examine the relation between pain and bone metastases in a group of patients with prostate or breast cancer that had been referred for bone scintigraphy. Whole-body bone scans, anterior and posterior views obtained with a dual detector gamma camera were studied from 101 consecutive patients who had undergone scintigraphy (600 MBq Tc-99m MDP) because of suspected bone metastatic disease. At the time of the examination, all patients were asked whether they felt any pain or had recently a trauma. This information was correlated with the classifications regarding the presence or absence of bone metastases made by a group of three experienced physicians. In patients with prostate cancer, we found metastases in 47% (18/38) of the patients with pain, but only in 12% (2/17) of the patients without pain (p = 0·01). In patients with breast cancer, on the other hand, metastases were more common in patients without pain (71%; 10/14) than in patients with pain (34%; 11/32) (p = 0·02). In conclusion, a significant relation between pain and skeletal metastases could be found in patients with prostate cancer and a reverse relation in patients with breast cancer

Plasma atropine concentrations associated with decreased intestinal motility in horses

IntroductionAtropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. Materials and methodsEight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plasma were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal motility was measured using borborygmi frequency and electrointestinography (EIG). Experimental data were analyzed using a non-linear mixed effects model. The model was then used to simulate different dosing regimens. ResultsAtropine significantly decreased borborygmi response and EIG response. Six horses developed clinical signs of abdominal pain. The pharmacokinetic typical values were 0.31, 1.38, 0.69, and 1.95 L/kg center dot h for the volumes of the central, the highly perfused, the scarcely perfused compartments, and the total body clearance, respectively. The pharmacodynamic typical values were 0.31 mu g/L and 0.6 and 207 nV(2)7 cpm for the plasma concentration at 50% of the maximum response and the maximum response and the baseline of cecal EIG response, respectively. Six different dosing regimens of topical atropine sulfate to the eye (0.4 and 1 mg every hour, every 3 h, and every 6 h) were simulated. ConclusionThe IV PK/PD data coupled with simulations predict that administration of 1 mg of topical atropine sulfate administered to the eye every hour or every 3 h will lead to atropine accumulation in plasma and decreased intestinal myoelectric activity. Administration every 6 h predicted a safe dosing regimen in full-sized horses. Clinical studies would be valuable to confirm the conclusions. For smaller equids and horses put at risk for colic due to othercauses, droplet bottles that deliver 40 mu l of 1% atropine sulfate per drop or less may be used to lower the risk further

A comparison of two imaging modalities for detecting lymphatic nodal spread in radiochemotherapy of locally advanced cervical cancer

Background and purpose: In uterine cervical cancer tumour spread reaching the para-aortic lymph nodes is the most significant independent pre-treatment predictor of progression-free survival. When introducing [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) in our clinic for patients with advanced cervical cancer planned for definitive radiochemotherapy, the purpose of this study was to quantify to what extent the added information lead to changes in radiotherapy planning. Material and methods: We included 25 consecutive patients with cervical cancer stages IB2 – IIIB planned for definitive radiochemotherapy between November 2010 and May 2012. The patients were examined both with magnetic resonance imaging (MRI) and FDG-PET/CT before treatment and after four weeks of treatment. Results: In 11/24 (46%) of the patients the FDG-PET/CT before treatment provided additional diagnostic information leading to changes in treatment planning compared to information from MRI. Seven of these eleven patients (64%) were alive and without evidence of disease at four-year follow-up. The MRI detected pelvic tumour spread not seen on the FDG-PET/CT in 2/24 patients. The disease-free four-year survival was 59%. Conclusions: Additional diagnostic information from FDG-PET/CT changed treatment strategy in almost half of the patients and may have increased chances of survival in this limited group of patients with locally advanced uterine cervical cancer. We recommend both modalities for nodal detection. Keywords: Cervical cancer, Nodal spread, Radiochemotherapy, FDG-PET/CT, MR

Boron neutron capture therapy (BNCT) for glioblastoma multiforme: A phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA)

Background and purpose: To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. Patient and methods: This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6 h. Neutron irradiation started 2 h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. Results: The boron-blood concentration during irradiation was 15.2-33.7 mu g/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. Conclusion: Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of B-10 in tumour cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved