The management of sex offenders: perspectives for psychiatry

In the effort to identify and manage sex offenders, the differences between legal and medical/psychiatric terminology and approaches are readily apparent. This article discusses the different definitions and approaches of the two fields and considers both the behaviors that create risk to others and the strategies for reducing that risk. Particular attention is paid to the subcategory of paraphilic sex offenders. Treatment goals, modalities, and efficacies are discussed, as are evolving legal strategies for risk control and the need for interaction between law and medicine/psychiatry in order to accomplish common goals of risk management.     

Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors

Background The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes.Patients and methodsWe retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan–Meier method and compared by Log-rank test.ResultsMedian age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (P = 0.006). Type I patients had inferior outcome than type II patients (P = 0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (P = 0.014), but not in type I LM. On multivariate analysis, administration of either intrathecal pharmacotherapy (P = 0.012) or systemic pharmacotherapy (P = 0.0003) was associated with improved outcome in type I LM, but not in type II LM.ConclusionThe EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.     

Polymerization of proteins into amyloid protofibrils shares common critical oligomeric states but differs in the mechanisms of their formation

Amyloid protofibril formation of phosphoglycerate kinase (PGK) and Syrian hamster prion protein (SHaPrP(90-232)) were investigated by static and dynamic light scattering, size exclusion chromatography and electron microscopy. Changes in secondary structure were monitored by Fourier transform infrared spectroscopy and by circular dichroism. Protofibril formation of the two proteins is found to be a two-stage process. At the beginning, an ensemble of critical oligomers is built up. These critical oligomeric states possess a predominant β-sheet structure and do not interact considerably with monomers. Initial oligomerization and transition to β-sheet structure are coupled events differing in their details for both proteins. Intermediate oligomeric states (dimers, trimers, etc.) are populated in case of PGK, whereas SHaPrP(90-232) behaves according to an apparent two-state reaction between monomers and octamers rich in β-structure with a reaction order varying between 2 and 4. All oligomers coalesce to PGK protofibrils in the second stage, while SHaPrP(90-232) protofibrils are only formed by a subpopulation. The rates of both growth stages can be tuned in case of PGK by different salts preserving the underlying generalized diffusion-collision mechanism. The different kinetics of the early misfolding and oligomerization events of the two proteins argue against a common mechanism of protofibril formation. A classification scheme for misassembly mechanisms of proteins based on energy landscapes is presented. It includes scenarios of downhill polymerization to which protofibril formation of PGK and SHaPrP(90-232) belong.     

The prognostic significance of Jun transcription factors in ovarian cancer

Purpose

The Jun proteins (c-Jun, JunD and JunB) play an important role in the regulation of cell proliferation, apoptosis and angiogenesis. It is well established that these proteins participate in the carcinogenesis and progression in several tumour types. However, little is known about the prognostic significance of Jun proteins in patients with invasive epithelial ovarian carcinoma.

Methods

We analysed fresh-frozen tissues of 161 ovarian cancer patients by using Western blot analysis to investigate protein levels of JunB, JunD, c-Jun and phosphorylated c-Jun (pc-Jun Ser63). The results were correlated with clinicopathologic prognostic parameters and survival data.

Results

A high pc-Jun expression was significantly associated with shorter progression-free survival (14 vs. 16 months, p = 0.017) and overall survival (25 vs. 41 months, p = 0.038). In case of JunD, moderate protein levels were associated with a better prognosis, leading to longer progression-free and overall survival compared to weak or strong JunD expression (PFS in cases with weak/moderate/strong JunD expression: 14 vs. 19.5 vs. 16 months, p = 0.011; OAS: 32 vs. 42 vs. 35.5 months, p = 0.009). Multivariate Cox regression analysis confirmed an independent and significant impact of pc-Jun and JunD on the patient’s prognosis.

Conclusions

Our results show that Jun proteins (pc-Jun and JunD) influence carcinogenesis and tumour progression, suggesting a significant role as prognostic predictors in human ovarian carcinoma.     

Characterization of non-calcified coronary atherosclerotic plaque by multi-detector row CT: comparison to IVUS

Multi-detector row Computed Tomography (MDCT) permits non-invasive visualization of the coronary arteries. The ability to visualize and, with limitations, to characterize non-calcified coronary atherosclerotic plaque has been described. We investigated the CT attenuation of non-calcified plaques as determined by 16-slice MDCT in comparison to intravascular ultrasound (IVUS). METHODS AND RESULTS: Thirty-two patients were investigated by contrast-enhanced 16-slice CT. In addition, IVUS of one coronary artery (motorized pullback) was performed (LM+LAD: 22, LM+LCX: 4, RCA: 6). At 252 sites within the coronary system, in which non-calcified atherosclerotic plaque could be identified both in MDCT and IVUS, the CT attenuation within the plaque was measured using a centrally placed region of interest and correlated to the appearance of the plaque in IVUS at the corresponding location. The mean CT attenuation within plaque that corresponded to hyper-echogenic appearance in IVUS was 121+/-34HU (n=76). The mean CT attenuation within plaque that corresponded to hypo-echogenic appearance was 58+/-43HU (n=176, p<0.001). However, there was substantial overlap of the density values measured by MDCT in the two groups. CONCLUSIONS: A significant difference of the mean CT attenuation within atherosclerotic lesions of hypo-echogenic and hyper-echogenic appearance in IVUS could be observed. However, we observed substantial overlap of attenuation values between plaque types so that the differentiation of "vulnerable" and "stable" plaques based on their CT attenuation is doubtful.     

Prospective gait analysis in patients with first metatarsophalangeal joint arthrodesis for hallux rigidus

BACKGROUND: Arthrodesis of the first metatarsophalangeal (MTP) joint is a common procedure with a proven long-term success rate. However, there is limited scientific information on its functional results. There is little data in the literature about changes in gait parameters after first MTP joint arthrodesis. The purpose of this study was to objectively evaluate the effects of first MTP joint arthrodesis on gait. METHODS: Twenty-three patients with symptomatic hallux rigidus refractory to nonoperative treatment were treated with first MTP joint arthrodesis. A prospective gait analysis study was performed on all patients at an average of 8.6 days before surgery and then again at least 1 year postoperatively. Preoperative and postoperative data from the patients were compared to determine differences in clinically relevant temporal-spatial, kinematic, and kinetic parameters of gait. RESULTS: There were three statistically significant changes in gait: increases in maximal ankle push-off power and single-limb support time on the involved extremity, and a decrease in step width. CONCLUSIONS: First MTP joint arthrodesis produces objective improvement in propulsive power, weightbearing function of the foot, and stability during gait.