Anatomic variants associated with peroneal tendon disorders: MR imaging findings in volunteers with asymptomatic ankles

PURPOSE: To evaluate prospectively, on magnetic resonance (MR) images in volunteers with asymptomatic ankles, various features of anatomic variants that are potentially associated with peroneal tendon disorders. MATERIALS AND METHODS: The study had institutional review board approval; informed consent was obtained from each volunteer. The prevalence of accessory peroneus quartus muscles, the location of the muscle-tendon junction of the peroneus brevis muscle, the prevalence and size of the peroneal tubercle and the retrotrochlear eminence, and the shape of the retromalleolar fibular groove were evaluated on MR images in 65 volunteers with asymptomatic ankles (35 women, 30 men; age range, 23-70 years; median age, 45 years). MR images were analyzed by two radiologists in consensus. The relationship between anatomic features and age and sex was analyzed by using Spearman rank correlation and the Wilcoxon rank sum test. RESULTS: A peroneus quartus muscle was identified in 11 (17%) ankles. Ninety percent of the musculotendinous junctions of the peroneus brevis muscle were located in a range between 27 mm proximal to and 13 mm distal to the fibular tip (median, 0 mm). A peroneal tubercle was identified in 36 (55%) ankles. Ninety percent of all peroneal tubercles were 4.6 mm or smaller (median height, 2.9 mm). A retrotrochlear eminence was seen in all ankles (median, 3.0 mm; 90% were 4.6 mm or smaller). The retromalleolar groove was concave in 18 (28%), flat in 28 (43%), convex in 12 (18%), and irregular in seven (11%) volunteers. A significant difference (P = .04) for the height of the retrotrochlear eminence was found between men (median, 3.4 mm) and women (median, 2.5 mm). All other P values were greater than .05. CONCLUSION: Anatomic variants thought to predispose individuals to peroneal tendon disorders can be seen in volunteers with asymptomatic ankles.     

Training physicians in shared decision-making-Who can be reached and what is achieved?

Objective

To report on experiences with a general shared decision-making (SDM) physician training program offered to physicians throughout Germany.

Methods

This study enrolled 150 physicians in an 8-h SDM training program. Physicians were assessed with standardized instruments before and after training. Main variables of interest were physician professional attributes, personality characteristics, attitudes, measures of training success (quality rating, knowledge, competency ratings), and variables associated with training success.

Results

The SDM training obtained positive quality ratings, led to an amelioration in an objective SDM knowledge test (p < .001), and highly improved physicians’ confidence in their SDM competencies (p < 0.001). It attracted experienced, middle-aged (45 years), male and female (46%) physicians, mostly office-based (2/3) general practitioners and internists (2/3). Most physicians (94%) reported positive attitudes towards SDM. They were securely attached (63%) with predominant social career choice motives (46%). Physicians with personality characteristics clashing with the SDM concept benefited mostly from the training.

Conclusion

A voluntary SDM training program is attractive to practicing physicians and effective in increasing SDM-related confidence and knowledge.

Practice implications

Even physicians who are highly motivated to use SDM can improve their skills and benefit from SDM training. The dissemination of SDM training programs should be encouraged.     

Cerebral MRI abnormalities associated with vigabatrin therapy

Purpose:   Investigate whether patients on vigabatrin demonstrated new-onset and reversible T₂-weighted magnetic resonance imaging (MRI) abnormalities.
Methods:   MRI of patients treated during vigabatrin therapy was reviewed, following detection of new basal ganglia, thalamus, and corpus callosum hyperintensities in an infant treated for infantile spasms. Patients were assessed for age at time of MRI, diagnosis, duration, and dose, MRI findings pre-, on, and postvigabatrin, concomitant medications, and clinical correlation. These findings were compared to MRI in patients with infantile spasms who did not receive vigabatrin.
Results:   Twenty-three patients were identified as having MRI during the course of vigabatrin therapy. After excluding the index case, we detected new and reversible basal ganglia, thalamic, brainstem, or dentate nucleus abnormalities in 7 of  22  (32%) patients treated with vigabatrin. All findings were reversible following discontinuation of therapy. Diffusion-weighted imaging (DWI) was positive with apparent diffusion coefficient (ADC) maps demonstrating restricted diffusion. Affected versus unaffected patients, respectively, had a median age of 11 months versus 5 years, therapy duration 3 months versus 12 months, and dosage  170  mg/kg/day versus 87 mg/kg/day. All affected patients were treated for infantile spasms; none of 56 patients with infantile spasms who were not treated with vigabatrin showed the same abnormalities.
Discussion:   MRI abnormalities attributable to vigabatrin, characterized by new-onset and reversible T₂-weighted hyperintensities and restricted diffusion in thalami, globus pallidus, dentate nuclei, brainstem, or corpus callosum were identified in 8 of 23 patients. Young age and relatively high dose appear to be risk factors.     

Expressions of Topoisomerase IIα and BCRP in Metastatic Cells are Associated with Overall Survival in Small Cell Lung Cancer Patients

The aim of this study was to investigate the mRNA expression levels of multidrug resistance-associated proteins in chemo-na?ve metastatic lung cancer cells and to determine the correlation with response to chemotherapy and overall survival. Metastatic cells were obtained by transbronchial fine needle aspiration biopsy of enlarged mediastinal lymph nodes in 14 patients with small cell lung cancer (SCLC) and 7 patients with non-small cell lung cancer (NSCLC). After cytological confirmation of lung cancer type, total RNA was extracted from biopsy samples and reverse transcribed to cDNA, and real-time PCR for the genes of interest [P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance protein (LRP) and topoisomerase IIα (TOPIIα)], was performed. We observed significantly decreased expression of BCRP and significantly increased expression of TOPIIα in metastatic SCLC cells compared to NSCLC. Furthermore, in SCLC high topoisomerase IIα and low BCRP expression levels positively correlated with longer overall survival. Our results showed higher expression levels of BCRP as well as lower levels of topoisomerase IIα in chemo-na?ve metastatic cells in NSCLC than in SCLC. These results correlate with previous observations that metastatic SCLC cells at the beginning of chemotherapy are potentially more sensitive to chemotherapeutic agents while in metastatic NSCLC cells resistance is usually inherent. We also showed that altered levels of topoisomerase IIα and BCRP in SCLC are important factors that contribute to resistance to chemotherapeutics that interfere with the enzyme and/or DNA and are highly associated with overall survival.     

PNUTS forms a trimeric protein complex with GABA(C) receptors and protein phosphatase 1

Phosphorylation and dephosphorylation of neurotransmitter receptors represent an important mechanism to regulate synaptic signal transduction. Here, we identified PNUTS, a targeting subunit of protein phosphatase 1 (PP1) as a new binding partner of GABA_C receptors. In the mammalian retina, PNUTS is co-expressed with GABA_C receptors and PP1 in bipolar cells. PNUTS and PP1 were detected in membrane protein preparations of the retina and precipitate with GABA_C receptor specific antibodies. Furthermore, PNUTS shuttles from the nucleus to the membrane in cells co-expressing GABA_C receptors. We show simultaneous binding of PP1 and GABA_C receptors to different domains of PNUTS, demonstrating that PNUTS cross-links PP1 and GABA_C receptors. Finally, modeling studies showed that the PP1 docking motif of PNUTS fits into the binding pocket on the enzyme surface, despite a C-terminal adjacent proline. We suggest that PNUTS targets PP1 to synaptic sites, acting as a temporary bridge between the phosphatase and GABA_C receptors.     

Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T-cell and IgG2a response

Single-stranded RNA oligonucleotides containing an immunostimulatory motif (immunostimulatory RNA [isRNA]) are potent inducers of interferon-alpha via the Toll-like receptor 7. We investigated the effect of isRNA on the development of an immune response. We show that isRNA activates dendritic cells and induces production of Th1-type cytokines both in vitro and in vivo. Cytokine production led to bystander activation of T and B cells. We further demonstrate that isRNA triggers the generation of antigen-specific cytotoxic T cells and of an IgG2a-biased antibody response to antigen in a sequence-dependent manner. In summary, we provide evidence for the first time that isRNA oligonucleotides can simultaneously activate the innate and adaptive arms of the immune system.     

Flexor tendon injuries in pediatric patients

PURPOSE: The purpose of this research was to study the incidence and outcome of flexor tendon injuries in pediatric patients. METHODS: A survey of flexor tendon repair in children less than 16 years of age was performed in the City of Helsinki during 2000-2005. A retrospective clinical outcome study of all consecutive 28 patients with 45 involved fingers treated in Children's Hospital was also performed at a mean 38 months (range 12-53 months) after surgery. Active motion program after multistrand tendon repair was used in 33 fingers, cast immobilization in 11 fingers, and elastic bands in 1 finger. Functional and cosmetic subjective result was evaluated by a visual analog scale (VAS, 0-100). Range of motion (ROM) of metacarpophalangeal (MCP) and interphalangeal (IP) joints were measured. Grip strength was recorded. Functional outcome methods of Buck-Gramcko, ASSH, Strickland, and distal interphalangeal joint (DIP) ROM methods were applied. RESULTS: The calculated annual incidence of finger flexor injury per child in Helsinki was 0.036 per 1000. There were no ruptures of the multistrand repairs with active motion program, but three 2-strand core sutures failed within 1 month of the repair. Mean functional and cosmetic VAS scores (all 28 patients) were 87 and 84. Mean ROM ratio of the DIP joint in zone 1 and 2 injuries was 60%, compared to 98% in zone 3 and 5 injuries. Ranges of motion of the proximal interphalangeal (PIP) and MCP joints were practically normal in all patients. There was a discrepancy among the functional outcome scores, with good and excellent results in all 45 fingers (Buck-Gramcko), in 39 fingers (ASSH), in 36 fingers (original Strickland), and in 32 fingers (DIP ROM). CONCLUSIONS: Flexor tendon injuries in children are rare. Both subjective and objective outcomes are generally good. Active motion program is an effective technique after multistrand flexor tendon repair at all levels in children. Range of motion of the DIP joint may be a more effective means of evaluating outcome in pediatric flexor tendon injuries. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.     

The three official language versions of the Declaration of Helsinki: what's lost in translation?

BACKGROUND: The Declaration of Helsinki, the World Medical Association's (WMA's) statement of ethical guidelines regarding medical research, is published in the three official languages of the WMA: English, French and Spanish. METHODS: A detailed comparison of the three official language versions was carried out to determine ways in which they differed and ways in which the wording of the three versions might illuminate the interpretation of the document. RESULTS: There were many minor linguistic differences between the three versions. However, in paragraphs 1, 6, 29, 30 and in the note of clarification to paragraph 29, there were differences that could be considered potentially significant in their ethical relevance. INTERPRETATION: Given the global status of the Declaration of Helsinki and the fact that it is translated from its official versions into many other languages for application to the ethical conduct of research, the differences identified are of concern. It would be best if such differences could be eliminated but, at the very least, a commentary to explain any differences that are unavoidable on the basis of language or culture should accompany the Declaration of Helsinki. This evidence further strengthens the case for international surveillance of medical research ethics as has been proposed by the WMA.     

Spectrum of molecular defects and mutation detection rate in patients with mild and moderate hemophilia A

The amount of residual F8 (FVIII:C) determines the clinical severity of hemophilia A. Recently, we showed that the mutation detection rate in severely affected male patients (FVIII:C<1% of normal) is virtually 100% when testing for the common intron 22-/intron 1- inversions and big deletions, followed by genomic sequencing of the F8 gene. Here we report on the spectrum of mutations and their distribution throughout the F8 gene sequence in 135 patients with moderate (n=23) or mild (n=112) hemophilia A. In contrast to the severe form of the disorder, analysis on the genomic level failed to detect the molecular defect in approximately 4% of the moderately and in approximately 12% of the mildly affected patients. A total of 36 of the mutations identified in this study are novel. The vast majority of the detected changes were missense. The newly detected amino acid substitutions were scored for potential distant or local conformational changes and influence on molecular stability for every single F8 domain with available structures, using homology modeling. Two molecular changes in the promoter region of the factor VIII gene (c.-112G>A and -219C>T), affecting the core segment (minimal promoter) were detected in two patients with mild hemophilia A. To our knowledge this is the first report on promoter mutations in the F8 gene.