Physician preferences for bone metastasis drug therapy in Canada.

BACKGROUND: Currently in Canada, several bone-targeted agents (btas) with varying characteristics are available for the prevention of skeletal-related events (sres) in patients with bone metastasis secondary to solid tumours. In the present study, we evaluated the preferences of physicians in Canada for the various attributes of the available btas. METHODS: Physicians treating patients with bone metastasis from solid tumours were invited to complete an online discrete-choice experiment. Respondents were asked to choose between pairs of hypothetical medications for virtual patients. Each hypothetical medication was described based on predefined key attributes: time until first sre, time until worsening of pain, medication-related annual risk of osteonecrosis of the jaw (onj), medication-related annual risk of renal impairment, and mode of administration. A random-parameters logit model was used to analyze the choices between hypothetical medications and thus infer physician preferences for medication attributes. RESULTS: Responses from the 200 physicians who completed the discrete-choice experiment suggested that months until first sre, risk of renal impairment, and months until worsening of pain were considered the most important attributes affecting choice of bta. The annual risk of onj was considered the least important attribute. CONCLUSIONS: When making treatment decisions about the choice of bta for patients with bone metastasis from solid tumours, delaying sres and worsening of pain, and reducing the risk of renal impairment are primary considerations for physicians in Canada.

Neuroimaging is useful for monitoring disease activity in linear scleroderma "en coup de sabre".

Scleroderma is a group of rare chronic connective tissue disorders characterized by collagen accumulation that causes tissue hardening with consequent fibrosis. Skin involvement is mostly frequent, although several internal organs can be impaired (heart, lungs, liver, etc.). In childhood, juvenile localized scleroderma (JLS) is more frequently observed; in this subtype cutaneous lesions predominate frequently on the limbs but also on the face and scalp; in this case, it is referred to as scleroderma "en coup de sabre" (ECDS). Neurological abnormalities have been described in association with ECDS as an effect of progressive scalp and underlying tissues involvement. Up to now, no validated biomarkers exist to evaluate disease evolution and, in this way, frequently diagnosis of central nervous system (CNS) involvement occurs when patients are already symptomatic. We describe the case of a 5-year old girl, with a diagnosis of ECDS characterized by the typical scalp lesion, with slight subsidence of the underlying diploe. In this case, radiological examination has been essential to evaluate the degree of progression of skin and soft tissues lesions and to clarify the right therapeutic approach. In selected JLS children, both MRI and CT with 3D reconstruction images provide a useful tool to monitor disease evolution and to address therapeutic choices.

Breast MRI artefacts: evaluation and solutions in 630 consecutive patients.

AIM: To evaluate the problems that may arise in breast magnetic resonance imaging (MRI) related to the presence of artefacts and pitfalls, in order to improve its accuracy, sensitivity, and specificity. MATERIALS AND METHODS: Six hundred and thirty breast MRI examinations performed using a 1.5 T magnet were analysed retrospectively. Each type of artefact that may have affected the correct interpretation of the acquired images was considered and analysed. In particular, the presence of technical artefacts, which are related to patient-dependent factors or to the examination itself, and non-technical artefacts, which are the result of inadequate and incorrect image interpretation occurring in absence of technical issues, were examined. In every case of suspicious findings, doubtful lesions were subjected to histological characterization for appropriate therapeutic planning. In the remainder of cases, patients underwent follow-up for at least 18 months. RESULTS: Artefacts were found in 33% of all examinations, among those 48.6% were caused by movement, 33.6% were due to non-homogeneous or failed fat saturation, 8.7% to incorrect positioning of the patient, 7.2% to metallic artefacts, 1.4% to aliasing, and 0.5% were "zebra artefacts". When the artefact was identified in a sequence, the sequence was performed a second time after corrective measures. No artefacts affected diagnostic interpretation of the obtained images. CONCLUSION: The present study provides a specific and precise review of the most frequent artefacts with a discussion of possible and practical solutions. A highly qualified team is required to perform accurate diagnostic tests and to limit or remove the possibility of misinterpretation.

Role of [18F]-FDG-PET/MDCT in evaluating early response in patients with Hodgkin's lymphoma.

PURPOSE: The authors evaluated the prognostic role of 18-fluoro-fluorodeoxyglucose positron emission tomography/multidetector computed tomography ([(18)F]-FDG PET/MDCT) in treating patients with Hodgkin's lymphoma (HL). MATERIALS AND METHODS: We retrospectively evaluated 132 patients with HL studied with PET/MDCT before the start of chemotherapy (CTX) for staging purposes and again after two CTX cycles with [doxorubicin (Adriblastin), bleomycin, vinblastine, dacarbazine (ABVD_] (interim PET/MDCT), at least 30 days after the end of the last CTX cycle and/or 3 months after the end of radiotherapy, if delivered (final PET-MDCT). RESULTS: Interim PET-MDCT was negative in 104/132 patients (79%), and their final PET-MDCT showed complete remission in 102/104 (98%) of cases, with disease recurrence/persistence in two (2%). In the remaining 28 (21%) patients, interim PET-MDCT revealed an early response in 68% of cases and chemoresistance with disease progression in 32% of cases; in these 28 patients, final PET-MDCT showed a lack of response to treatment in 43% of cases (43%) and complete remission in 57% of cases. Statistical analysis of these data showed that interim PET-MDCT had a negative predictive value of 98% and a positive predictive value of 42%, with values of sensitivity, specificity and diagnostic accuracy of 85.7%, 86.4% and 86.4%, respectively. CONCLUSIONS: Interim PET-MDCT has a reliable prognostic role in diagnosis and treatment of patients with HL, as it helps predict which patients are more likely to achieve a complete response at the end of treatment. PET/MDCT may also lead to a change in treatment, with reduced treatment-related toxic effects and significantly reduced total costs.

Cost-effectiveness of two breast biopsy procedures: surgical biopsy versus vacuum-assisted biopsy.

PURPOSE: The aim of this study was to compare the cost-effectiveness of two breast biopsy procedures: surgical biopsy and vacuum-assisted biopsy (VAB). MATERIALS AND METHODS: Between November 2008 and September 2009, 200 patients with suspicious breast lesions underwent biopsy procedures at our radiology department: 100 underwent VAB and 100 underwent surgical biopsy. 66 lesions were sampled under sonographic guidance, 109 under mammographic guidance and 25 under magnetic resonance guidance. RESULTS: All procedures were successfully completed. No significant differences in diagnostic efficacy were found between the biopsy procedures. Surgical biopsy has a higher unit cost compared with VAB. CONCLUSIONS: Our analysis emphasises the benefits of VAB compared with surgical biopsy in terms of both cost-effectiveness, and less invasiveness from a psychological and aesthetic point of view.

Value of the correct diagnostic pathway through conventional imaging (mammography and ultrasound) in evaluating breast disease.

PURPOSE: This study evaluated the role of the correct diagnostic pathway through conventional imaging in evaluating breast disease. MATERIALS AND METHODS: Six hundred patients aged between 35 and 75 years were enrolled in the study. All patients underwent detailed history and clinical examination, ultrasound (US) and mammography. US scans were repeated after mammography. All suspicious lesions were studied by cytological and histological characterisation and magnetic resonance (MR) imaging. RESULTS: The first US scan showed 147 solid lesions, 67 lesions characterised by posterior acoustic shadowing and 193 areas of heterogeneous echostructure. The second US scan, performed after mammography, confirmed 123/147 solid nodular lesions, 53/67 lesions characterised by posterior acoustic shadowing and 183/193 areas of heterogeneous echostructure; it also showed 13 nodular lesions not seen on the first scan and two cases of nodular lesions with irregular calcifications. CONCLUSIONS: Our experience suggests that US not performed in conjunction with mammography gives rise to incorrect diagnostic interpretations (either false positive or false negative results). The detection rate of the US scan performed after mammography increases from 4.16% to 5.5%.

Anatomical and functional evaluation of the myocardium in patients with acute coronary syndrome (NSTEMI) using MR imaging.

PURPOSE: The aim of our study was to evaluate the role of magnetic resonance (MR) imaging in identifying the location and extent of acute ischaemic injury to predict reversibility and distinguish areas of acute from chronic ischaemia in patients with acute coronary syndrome non- ST-elevation myocardial infarction (NSTEMI). MATERIALS AND METHODS: We evaluated 22 patients with NSTEMI acute coronary syndrome confirmed by coronary angiography (CA). We studied ventricular function indices and segmental changes in wall thickness and kinetics by cine-MR imaging sequences. Subsequently, we evaluated myocardial wall oedema with T2-weighted black-blood short-tau inversion recovery turbo spin echo (T2 BB-STIRTSE) sequences and identified areas of myocardial necrosis using T1-weighted turbo field-echo inversion recovery (T1 TFE-IR) sequences after contrast material administration. RESULTS: The results obtained with the single sequences were as follows: T2 BB-STIR-TSE: 96.8% sensitivity, 100% specificity, 99.7% negative predictive value, 99.7% positive predictive value; T1 TFE-IR: 45.8% sensitivity, 96.9% specificity, 92.3% negative predictive value, 90.3% positive predictive value; systolic wall thickening: 87.5% sensitivity, 91.8% specificity, 98.7% negative predictive value, 50% positive predictive value, 91.4% accuracy. CONCLUSIONS: Our study suggests that the sequences used for evaluating oedema and assessing viability allow for precise localisation and differentiation of areas of acute and chronic ischaemia by quantifying the possible mismatch between ischaemia and necrosis.

Ménétrier's disease diagnosed by enteroclysis CT: a case report and review of the literature.

This study reports a case of Ménétrier's disease (MD) in an adult who presented with epigastric pain and peripheric edema. We focused in particular on the imaging and diagnostic aspects of the presenting case as well as clinical, histologic, and therapeutic aspects. Computed tomography (CT) enteroclysis is a new imaging technique which combines enteroclysis and spiral multislice CT. To the best of our knowledge this is the first report on a MD in an adult patient diagnosed by CT Enteroclysis.

Cost-effectiveness analysis of two vacuum-assisted breast biopsy systems: Mammotome and Vacora.

PURPOSE: This study was undertaken to compare the cost effectiveness of two vacuum-assisted breast biopsy devices, the Mammotome and Vacora systems. MATERIALS AND METHODS: Between January and June 2006, 238 vacuum-assisted breast biopsies were performed at our radiology department. Five out of 238 lesions were excluded because of inadequate sampling. The Mammotome system was used in 108/233 lesions and the Vacora system in 125/233. Fifty-eight lesions underwent ultrasound-guided breast biopsy, and 50 lesions underwent mammography-guided biopsy with both Mammotome and Vacora devices. Magnetic-resonance-guided biopsy was possible with the Vacora system only (17/125 lesions). RESULTS: All procedures were successfully completed. No significant differences were found between the results of the Mammotome and Vacora biopsies in terms of effectiveness: sensitivity was 84.4% and 86.2%, respectively, and specificity 100%. In terms of cost, the Mammotome system has higher costs per procedure compared with the Vacora. CONCLUSIONS: Our clinical results confirm the diagnostic accuracy of both the Mammotome and Vacora systems, whereas our cost analysis shows that there is a considerable difference, mostly related to the initial investment.

Effects of GYKI 52466 and some 2,3-benzodiazepine derivatives on hippocampal in vitro basal neuronal excitability and 4-aminopyridine epileptic activity.

In order to determine whether the anticonvulsant effect of 2, 3-benzodiazepines is also displayed in a model of in vitro epilepsy, such as the "epileptiform" hippocampal slice, we studied the effects of 2,3-benzodiazepine 1-(4-aminophenyl)-4-methyl-7, 8-methylenedioxe-5H 2,3-benzodiazepine hydrochloride (GYKI 52466) and some new 2,3-benzodiazepine derivatives on CA1 basal neuronal excitability and on CA1 epileptiform burst activity produced by 4-aminopyridine in rat hippocampal slices. The results showed that GYKI 52466 affected basal neuronal excitability as evidenced by its influence on the magnitude of the CA1 orthodromic-evoked field potentials. 2,3-Benzodiazepines showed their antiepileptic effect also in an in vitro model of experimental epilepsy. The effects of the new 2,3-benzodiazepine derivatives suggest that the methylenedioxidation in positions 7 and 8 of the 2,3-benzodiazepine ring is the main structural modification for the antiepileptic effect of 2,3-benzodiazepines to take place.

Effects of the novel acetylcholinesterase inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine on locomotor activity and avoidance learning in mice.

The acetylcholinesterase reversible inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine (THA-C8) is a new synthesized derivative of tacrine (THA) characterized by an alkyl chain in the molecular structure which ameliorates the penetrability of the compound into the central nervous system. THA-C8 (0.1-5 mg/kg) significantly reduced spontaneous locomotor activity in CD1 mice at a dose of 3 mg/kg. Moreover, THA-C8 (0.2-2 mg/kg) significantly improved shuttle-box avoidance acquisition at doses (0.25, 0.3, 1 mg/kg) not affecting locomotion and that are much lower than the doses reported to be effective for THA in animal models. From the data reported it seems that the new compound could be interesting for therapeutic purposes.

Studies on a new series of THA analogues: effects of the aromatic residues that line the gorge of AChE.

A series of N-monoalkylsubstituted 1,2,3,4-tetrahydro-9-aminoacridines have been prepared after modelling simulation of the AChE-inhibitor complex. Molecular modelling has predicted a number of hydrophobic residues to be involved in the catalytic mechanism of this interaction between the binding sites of AChE and this series of aminoacridines. In these compounds the acridine moiety becomes sandwiched between the rings of PHE330 and TRP84. In particular, the alkyl chain shows the important role of aromatic groups as binding sites. Their in vitro inhibitory properties (enzyme from Electrophorus electricus) confirm the aromatic groups as a general and significant characteristic of the mechanism of AChE inhibition.

Synthesis and cholinesterase inhibitory activity of 6-, 7-methoxy-(and hydroxy-) tacrine derivatives.

Some 6- and 7-methoxy-(and hydroxy-) tacrine derivatives were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities. The most potent analogue in our series was the 9-heptylamino-6-methoxytacrine 3af which, in comparison with tacrine (THA), displayed an almost identical inhibitory effect, slightly lower acute toxicity and higher selectivity profile towards AchE when compared with THA.

Effects of the new A2 adenosine receptor antagonist 8FB-PTP, an 8 substituted pyrazolo-triazolo-pyrimidine, on in vitro functional models.

1. We have characterized the in vitro pharmacological profile of putative A2 adenosine antagonists, two non-xanthine compounds, 5-amino-8-(4-fluorobenzyl)-2-(2-furyl)-pyrazolo [4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (8FB-PTP) and 5-amino-9-chloro-2-(2-furyl 1,2,4-triazolo [1,5-c] quinazoline (CGS 15943), and the xanthine derivative (E)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropyl- xanthine (KF 17837). 2. In binding studies on bovine brain, 8FB-PTP was the most potent (Ki = 0.074 nM) and selective (28 fold) drug on A2 receptors, whereas CGS 15943 and KF 17837 exhibited affinity in the low and high nanomolar range, respectively, and showed little selectivity. 3. In functional studies, 8FB-PTP antagonized 5'-N-ethyl-carboxamidoadenosine (NECA)-induced vasorelaxation of bovine coronary artery (pA2 = 7.98) and NECA-induced inhibition of rabbit platelet aggregation (pA2 = 8.20). CGS 15943 showed weak activity in the platelet aggregation model (pA2 = 7.43) and failed to antagonize NECA-induced vasodilatation. KF 17837 was ineffective in both models up to micromolar concentrations. 4. Antagonism of A1-mediated responses was tested versus 2-chloro-N6-cyclopentyladenosine (CCPA) in rat atria. 8FB-PTP and CGS 15943 also antagonized competitively the negative chronotropic response induced by CCPA. Conversely, KF 17837 was unable to reverse A1-mediated responses. 5. 8FB-PTP is a potent and competitive antagonist of responses mediated by A2 adenosine receptors. The data provided a basis to reduce, by further chemical modifications, the affinity at A1 receptor and therefore enhance A2 receptor selectivity.

Physostigmine analogs anticholinesterases: effects of the lengthening of the N-carbamic chain on the inhibition kinetics.

Data are presented about the inhibitor power of new carbamates against acetylcholinesterase. The study was carried out on two series of physostigmine analogs, N-alkyl and N-methyl,N-alkylphysostigmines. For these inhibitors, the second-order rate constants for inhibition, ki, and the first-order rate constants of reactivation, k3, have been determined. From the reported results, electronic, hydrophobic and steric effects, due to the enhancement of the alkyl chain, may have influenced all kinetics parameters discussed. In comparison to physostigmine, both the new N-methyl,N-alkylphysostigmines and the N-alkylphysostigmines showed a non-linear decrease in the values of ki and k3. This study presents the hydrophobic interactions as an important factor not only in determining carbamylation but also decarbamylation rates constants.

Synthesis and antileishmanial activity of some 1- or 2-(dihydroxyalkyl) and 3-(dihydroxyalkoxy)pyrazolo [3,4-d] pyrimidines.

Several new derivatives of 4-amino-, 4,6-diamino- and 4-hydrazino-[3,4-d]pyrimidine dihydroxyalkyl substituted in the 1 or 2 positions, or dihydroxyalkoxy substituted in the 3 position have been synthesized. Some of these compounds were evaluated for their activity against Leishmania infantum in mice. The highest degree of antileishmanial activity was displayed by the 4-amino-1-(dihydroxyalkyl) derivatives which yielded parasite inhibition values nearly comparable with that of glucantime in a standard 5-day test.