Magnetic resonance elastography with guided pressure waves

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.     

Serum antimuscarinic activity after a single dose of oral scopolamine hydrobromide solution measured by radioreceptor assay

Radioreceptor assay (RRA) was used to evaluate serum antimuscarinic activity in 10 healthy volunteers after a single dose of scopolamine hydrobromide (ScHBr) solution, 0.02 mg/kg, by a new oral administration method. Cardiac, antisialogogue, and subjective effects of the drug were also recorded. Although clinically useful antisialogogue and sedative effects were obtained 40 to 60 minutes after the administration of ScHBr, no reliable antimuscarinic activity was evaluated in serum samples for up to 3 hours. Clinically useful sedative and antisialogogue effects can be reached by gastrointestinal absorption of ScHBr solution.     

Interaction of psychotropic drugs with brain muscarinic cholinoceptors: similarities of biperiden with pirenzepine in receptor binding properties

It is generally accepted that there are at least three different subtypes of muscarinic cholinoceptors, pirenzepine being considered a selective M1 antagonist. In the present study, a number of different types of psychotropic drugs have been compared with pirenzepine and atropine as reference antimuscarinic drugs regarding their affinities for rat brain muscarinic cholinoceptors with the help of in vitro receptor binding studies. The most potent drugs, inhibiting 3H-1-quinuclidinyl benzilate (3H-QNB) binding at subnanomolar concentrations, were the antimuscarinic drugs scopolamine and atropine. Biperiden, promethazine, pirenzepine and some tricyclic antidepressants (amitriptyline, doxepin) were the next potent drugs, with IC50-values between 8.4 nM and 190 nM. The inhibition curves were steep and parallel giving Hill coefficients close to unity in all but two drugs studied. These exceptions were biperiden and pirenzepine both with Hill coefficients about 0.55. Thus, in addition to pirenzepine also biperiden seems to bind to the M1 receptor selectively. Additional receptor and functional studies are warranted to further elucidate the possible similarities of these two drugs.     

PCR and direct fluorescent-antibody staining confirm Chlamydia trachomatis antigens in swabs and urine below the detection threshold of Chlamydiazyme enzyme immunoassay.

In order to test the hypothesis that specimens blocking with a neutralizing reagent below the cutoff of the Chlamydiazyme enzyme immunoassay represent infected patients, we used direct fluorescent-antibody staining for elementary bodies (EBs) and PCR to confirm results for cervical swabs collected from 55,963 women and urethral swabs or first-void urine (FVU) samples collected from 5,781 men attending physicians' offices in the Toronto, Canada, area. Within a grey zone arbitrarily selected to represent values up to 40% below the positive threshold of the test run, 134 cervical swabs, 44 urethral swabs, and 39 FVU specimens exhibited a blocking response ( > 50% reduction in signal). Three or more EBs were observed in each of 98 cervical swabs (73.1%), 38 urethral swabs (86.4%), and 21 FVU specimens (53.8%). Of the 36 cervical swabs with fewer than three EBs, 33 were PCR positive; the positive PCR results for male specimens were 6 of 6 urethral swabs and 17 of 18 FVU samples. Application of the blocking test to specimens negative in the Chlamydiazyme enzyme immunoassay but having optical densities within 40% of the cutoff added 14.2% (217 of 1,531 specimens) more positive results to the survey. A total of 213 of 217 samples (98.2%) were reconfirmed as having EBs or DNA.     

Transitioning outcome measures: relationship between the CMTPedS and CMTNSv2 in children,adolescents, and young adults with Charcot‐Marie‐Tooth disease

Long‐term studies of Charcot‐Marie‐Tooth (CMT) disease across the entire lifespan require stable endpoints that measure the same underlying construct (e.g., disability). The aim of this study was to assess the relationship between the CMT Pediatric Scale (CMTPedS) and the adult CMT Neuropathy Score (CMTNSv2) in 203 children, adolescents, and young adults with CMT. There was a moderate curvilinear correlation between the CMTPedS and the CMTNSv2 (Spearman's rho ρ = 0.716, p < 0.0001), although there appears to be a floor effect of the CMTNSv2 in patients with a milder CMT phenotype. Univariate analyses indicate that the relationship between the CMTPedS and CMTNSv2 scores improves with worsening disease severity and advancing age. Although one universal scale throughout life would be ideal, our data supports the transition from the CMTPedS in childhood to the CMTNSv2 in adulthood as a continuum of measuring lifelong disability in patients with CMT.     

Immunohistochemical Detection of the Putative Mechanoproteins ASIC2 and TRPV4 in Avian Herbst Sensory Corpuscles

The avian Herbst corpuscles are the equivalent of the Pacinian corpuscles in mammals, and detect vibration and the movement of joints and feathers. Therefore, they can be regarded as rapidly adapting low‐threshold mechanoreceptors. In recent years, it has been establish that some ion channels are involved in mechanosensation and are present in both mechanosensory neurons and mechanoreceptors. Here we have used immunohistochemistry to localize some putative mechanoproteins in the Herbst corpuscles from the rictus of Columba livia. The proteins investigated were the subunits of the epithelial Na⁺ channel (ENaC), the transient‐receptor potential vanilloid 4 (TRPV4), and the acid‐sensing ion channel 2 (ASIC2). Immunoreactivity for ENaC subunits was never found in Herbst corpuscles, while the axon expressed ASIC2 and TRPV4 immunoreactivity. Moreover, TRPV4 was also detected in the cell forming the inner core. The present results demonstrate for the first time the occurrence of mechanoproteins in avian low‐threshold mechanoreceptors and provide further evidence for a possible role of the ion channels in mechanosensation. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.     

Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome

Background

Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments.

Methods

We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3–6) after the onset of MMF treatment. The characteristics of responder patients (n?=?74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients (n?=?22) were compared by univariate analysis and multivariate logistic regression.

Results

Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8–30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p?=?0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p?=?0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p?=?0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR?=?0.80, 95 % CI [0.69, 0.93], p?<?0.01).

Conclusions

MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug.