A prospective analysis of CT density measurements of bone metastases after treatment with zoledronic acid

Objective The objective was to prospectively determine CT density changes in bone metastases, before and after intravenous zoledronic acid for a maximum period of 12 months. Patients and methods Twenty-three consecutive patients presented with bone metastases and underwent therapy with zoledronic acid from December 2004. All patients underwent CT of the chest, abdomen, and pelvis. Bone density, measured in Hounsfield units (HU), was determined by segmenting lesions in the same anatomical area of the metastasis sites on the axial images of the sequential series of CT examinations. The effects of zoledronic acid were evaluated by calculating absolute and relative increases in bone density. Results The patients presented with multiple metastases in 65% of the cases. When compared with the baseline, all groups demonstrated a significant increase in bone density, which significantly (p < 0.01) correlated with the number of zoledronic acid administrations. There was increased bone density of at least 100% in 57%, and an increase of at least 50% in 87% of the patients. This increase was significant in both lytic and sclerotic metastases after 3 months of therapy. No significant bone density difference was found in normal-appearing bone. Conclusion Bone density measured by CT increases at metastatic sites after zoledronic acid treatment, regardless of the type of metastasis, in contrast to apparently normal bone.     

Incidence of new fractures in women with osteoporosis-induced vertebral fractures detected on routine lateral chest radiographs

Purpose

Vertebral fractures represent one of the major complications of osteopororis. Diagnosis is followed by a pharmacological, interventional or surgical treatment. Up to day there are non practice guidelines for a screening evaluation of bone fractures in elderly and most of the fractures remain undiagnosed. We prospectively evaluated the prevalence of vertebral fractures on chest X-rays to determine the diagnostic and prognostic roles of chest X-ray in predicting new bone fractures 2 years after the initial radiogram.

Materials and methods

Between March 2004 and October 2005, 4,045 women underwent chest X-ray in our radiology department for any indication. We identified 166 women with the presence of at least one vertebral fracture. A questionnaire was administered to these women to collect information about diagnosis of osteoporosis, history of malignancy, systemic diseases, osteoporosis-inducing drugs and pharmacological, radiological or surgical treatment received.

Results

Out of the 166 women (age 73±10.5 years) with vertebral fractures, we interviewed 101 women; 13 had died and 52 were not found. Most of the patients were on menopause (97.1%, 98/101) with an average age of menopause of 48,2 years (±6 years). Among the patients on menopause, 15,8% (16/101) had undergone hysterectomy. All patients received a diagnosis of osteoporosis, which was reached with a chest X-ray report in 23.7% (24/101) of cases. A new skeletal fracture occurred in 20.5% (5/27) of patients receiving treatment against a frequency of 20.8% (16/74) in patients without treatment. No statistical difference was found between the groups (p = 0.374).

Conclusions

Inadequate treatment may explain the lack of a substantial difference in new fracture risk between treated and untreated patients. For these reason we discuss about the evaluation of an adeguate therapeutic approaches in prevention of osteoporosis-induced fractures.     

芳香疗法对躯体疾病相关性失眠治疗作用的Meta分析

目的评价芳香疗法对躯体疾病相关性失眠的影响。方法检索电子数据库Pubmed、ScienceDirect、中国生物医学文献数据库（CBM）、外文医学信息资源检索平台（FMRS）、中国知网（CNKI）、 万方数据资源系统和维普期刊资源整合服务平台（VIP）等关于芳香疗法对于躯体疾病相关性失眠研究的随机对照实验。由2名研究者独立筛选文献和提取有效数据,采用RevMan5.3软件进行Meta分析。结果纳入7篇文献,共508例患者。Meta分析结果显示,芳香疗法对躯体疾病相关性失眠的作用优于对照组（P<0.01）。结论芳香疗法可以改善躯体疾病相关性失眠的睡眠质量。因此,推荐临床将芳香疗法作为补充疗法,用于改善躯体疾病相关性失眠的症状。     

Proton MRS of the unilateral substantia nigra in the human brain at 4 tesla: detection of high GABA concentrations.

Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra (SN), the cause of which is unknown. Characterization of early SN pathology could prove beneficial in the treatment and diagnosis of PD. The present study shows that with the use of short-echo (5 ms) Stimulated-Echo Acquisition Mode (STEAM) spectroscopy and LCModel, a neurochemical profile consisting of 10 metabolites, including gamma-aminobutyric acid (GABA), glutamate (Glu), and glutathione (GSH), can be measured from the unilateral SN at 4 tesla. The neurochemical profile of the SN is unique and characterized by a fourfold higher GABA/Glu ratio compared to the cortex, in excellent agreement with established neurochemistry. The presence of elevated GABA levels in SN was validated with the use of editing, suggesting that partial volume effects were greatly reduced. These findings establish the feasibility of obtaining a neurochemical profile of the unilateral human SN by single-voxel spectroscopy in small volumes.     

Effective connectivity between superior temporal gyrus and Heschl's gyrus during white noise listening: linear versus non-linear models

Purpose:

This fMRI study is about modelling the effective connectivity between Heschl’s gyrus (HG) and the superior temporal gyrus (STG) in human primary auditory cortices.

Materials & methods:

Ten healthy male participants were required to listen to white noise stimuli during functional magnetic resonance imaging (fMRI) scans. Statistical parametric mapping (SPM) was used to generate individual and group brain activation maps. For input region determination, two intrinsic connectivity models comprising bilateral HG and STG were constructed using dynamic causal modelling (DCM). The models were estimated and inferred using DCM while Bayesian Model Selection (BMS) for group studies was used for model comparison and selection. Based on the winning model, six linear and six non-linear causal models were derived and were again estimated, inferred, and compared to obtain a model that best represents the effective connectivity between HG and the STG, balancing accuracy and complexity.

Results:

Group results indicated significant asymmetrical activation (p_uncorr < 0.001) in bilateral HG and STG. Model comparison results showed strong evidence of STG as the input centre. The winning model is preferred by 6 out of 10 participants. The results were supported by BMS results for group studies with the expected posterior probability, r = 0.7830 and exceedance probability, ϕ = 0.9823. One-sample t-tests performed on connection values obtained from the winning model indicated that the valid connections for the winning model are the unidirectional parallel connections from STG to bilateral HG (p < 0.05). Subsequent model comparison between linear and non-linear models using BMS prefers non-linear connection (r = 0.9160, ϕ = 1.000) from which the connectivity between STG and the ipsi- and contralateral HG is gated by the activity in STG itself.

Conclusion:

We are able to demonstrate that the effective connectivity between HG and STG while listening to white noise for the respective participants can be explained by a non-linear dynamic causal model with the activity in STG influencing the STG-HG connectivity non-linearly.     

Differentiation of normal and neoplastic bone tissue in dynamic gadolinium-enhanced magnetic resonance imaging: validation of a semiautomated technique

Purpose

This study was undertaken to clinically validate the accuracy of a semiautomated software tool for analysing the enhancement curve in focal malignant bone lesions.

Materials and methods

Twenty-three patients affected by cancer with malignant focal bone lesions underwent dynamic gadolinium-enhanced magnetic resonance (MR) imaging using the following protocol: T1-weighted turbo spin-echo sequences (time to repeat [TR] 600 ms, time to echo [TE] 8.6 ms, field of view [FOV] 40×40 cm) before and after intravenous injection of gadolinium-containing contrast agent. Image postprocessing was performed using the software DyCoH. Each region of interest (5×5 pixels), drawn to include the area of the lesion with the highest values of the area under the curve map, was analysed to obtain time-intensity curves and relative perfusion parameters: time to peak (TTP), peak intensity (PI), slope (60-s slope), intensity at 60 s after contrast agent injection (60-s I) and final intensity (FI).

Results

Data were obtained by analysing 86 malignant lesions and 86 apparently normal bone regions. PI, 60-s slope, 60-s I and FI were significantly different between neoplastic and apparently normal (p<0.001) samples. Sensitivity, specificity and accuracy were, respectively, 94%, 93% and 94% at a PI threshold of 100 (signal-to-noise ratio), with positive and negative predictive values of 93% and 94%. At a threshold value of 0.85 for 60-s slope, sensitivity and specificity values were both 91%.

Conclusions

The semiautomated technique we report appears to be accurate for identifying neoplastic tissue and for mapping perfusion parameters, with the added value of a consistent measurement of perfusion parameters on colour-coded maps.     

Tardive Dyskinesia

Tardive dyskinesia (TD) is iatrogenic (drug-induced); hence the best strategy is prevention. Try to limit exposure to any dopamine receptor blocking agents (DRBAs) if possible. These agents may be unavoidable in some psychiatric conditions such as schizophrenia, but alternative therapies can be used in many situations, such as in the treatment of depression, anxiety, gastrointestinal conditions, and other neurologic conditions, including migraines and sleep disorders. When DRBAs are necessary, physicians should prescribe the smallest possible dose and try to taper and stop the drug at the earliest signs of TD. Abrupt cessation should be avoided, as this can worsen symptoms of TD. Always discuss and document the possibility of TD as an adverse effect when starting patients on DRBAs. If TD is mild and tolerable, the withdrawal of the offending agent is possible, and exposure to DRBAs was short, physicians should consider avoiding treatment and waiting for spontaneous recovery. When treatment is necessary, tetrabenazine (TBZ) is considered a potential first-line agent and is known to be one of the most effective drugs in treating TD, but it is expensive and adverse effects such as depression, akathisia and parkinsonism frequently occur. Therefore, second-line agents with better tolerability profiles are often tried first in practice. These include amantadine, benzodiazepines, beta-blockers, and levetiracetam. When using TBZ, adverse effects should be aggressively monitored. (Depression often can be managed with antidepressants, for instance). In patients with psychosis, withdrawal of the antipsychotic may not be possible. Switching to clozapine or quetiapine is one option to minimize TD. When these agents are contraindicated and the patient must continue using other atypical antipsychotic drugs, try to add dopamine-depleting agents such as TBZ or reserpine, but watch for the development of parkinsonism. When the symptoms are focal, such as tongue protrusion or blepharospasm, botulinum toxin injections can be very effective if spontaneous recovery does not occur. As a last resort, when disabling, life-threatening symptoms of TD persist despite all of the above-mentioned methods, some advocate resuming treatment with the DRBA to suppress symptoms of TD. This has the potential to worsen TD in the long run.     

De novo microdeletions of chromosome 6q14.1-q14.3 and 6q12.1-q14.1 in two patients with intellectual disability - further delineation of the 6q14 microdeletion syndrome and review of the literature

Interstitial 6q deletions can cause a variable phenotype depending on the size and location of the deletion. 6q14 deletions have been associated with intellectual disability and a distinct pattern of minor anomalies, including upslanted palpebral fissures with epicanthal folds, a short nose with broad nasal tip, anteverted nares, long philtrum, and thin upper lip. In this study we describe two patients with overlapping 6q14 deletions presenting with developmental delay and characteristic dysmorphism. Molecular karyotyping using array CGH analysis revealed a de novo 8.9 Mb deletion at 6q14.1-q14.3 and a de novo 11.3 Mb deletion at 6q12.1-6q14.1, respectively. We provide a review of the clinical features of twelve other patients with 6q14 deletions detected by array CGH analysis. By assessing all reported data we could not identify a single common region of deletion. Possible candidate genes in 6q14 for intellectual disability might be FILIP1, MYO6, HTR1B, and SNX14.     

Adenopatía intramamaria metastásica como única manifestación de carcinoma mamario

Intramammary lymph nodes are detected in 5% of screening mammographies. Sufficient grounds for histological examination to exclude malignancy are the absence of the hilar fatty radiolucent notch, a reduction in the volume of the central echogenic hilum, size greater than 1 cm or an increase in size compared with previous screens.