Primary amyloidosis of lower urinary tract

Primary amyloidosis of the lower urinary tract is a rare condition with an excellent prognosis in most cases. Three patients with this condition are described. In the cases of localized amyloidosis of the urethra and urinary bladder, the clinical presentation mimicked cancer of the respective sites. This was also true in the case of primary systemic amyloidosis involving the bladder. If significant associated systemic or local disease can be excluded, management is symptomatic and expectant.     

Activity of vestibular nuclei neurons during vestibular and optokinetic stimulation in the alert mouse

As a result of the availability of genetic mutant strains and development of noninvasive eye movements recording techniques, the mouse stands as a very interesting model for bridging the gap among behavioral responses, neuronal response dynamics studied in vivo, and cellular mechanisms investigated in vitro. Here we characterized the responses of individual neurons in the mouse vestibular nuclei during vestibular (horizontal whole body rotations) and full field visual stimulation. The majority of neurons ( approximately 2/3) were sensitive to vestibular stimulation but not to eye movements. During the vestibular-ocular reflex (VOR), these neurons discharged in a manner comparable to the "vestibular only" (VO) neurons that have been previously described in primates. The remaining neurons [eye-movement-sensitive (ES) neurons] encoded both head-velocity and eye-position information during the VOR. When vestibular and visual stimulation were applied so that there was sensory conflict, the behavioral gain of the VOR was reduced. In turn, the modulation of sensitivity of VO neurons remained unaffected, whereas that of ES neurons was reduced. ES neurons were also modulated in response to full field visual stimulation that evoked the optokinetic reflex (OKR). Mouse VO neurons, however, unlike their primate counterpart, were not modulated during OKR. Taken together, our results show that the integration of visual and vestibular information in the mouse vestibular nucleus is limited to a subpopulation of neurons which likely supports gaze stabilization for both VOR and OKR.     

Vestibuloocular reflex dynamics during high-frequency and high-acceleration rotations of the head on body in rhesus monkey

For frequencies >10 Hz, the vestibuloocular reflex (VOR) has been primarily investigated during passive rotations of the head on the body in humans. These prior studies suggest that eye movements lag head movements, as predicted by a 7-ms delay in the VOR reflex pathways. However, Minor and colleagues recently applied whole-body rotations of frequencies < or =15 Hz in monkeys and found that eye movements were nearly in phase with head motion across all frequencies. The goal of the present study was to determine whether VOR response dynamics actually differ significantly for whole-body versus head-on-body rotations. To address this question, we evaluated the gain and phase of the VOR induced by high-frequency oscillations of the head on the body in monkeys by directly measuring both head and eye movements using the magnetic search coil technique. A torque motor was used to rotate the heads of three Rhesus monkeys over the frequency range 5-25 Hz. Peak head velocity was held constant, first at +/-50 degrees /s and then +/-100 degrees /s. The VOR was found to be essentially compensatory across all frequencies; gains were near unity (1.1 at 5 Hz vs. 1.2 at 25 Hz), and phase lag increased only slightly with frequency (from 2 degrees at 5 Hz to 11 degrees at 25 Hz, a marked contrast to the 63 degrees lag at 25 Hz predicted by a 7-ms VOR latency). Furthermore, VOR response dynamics were comparable in darkness and when viewing a target and did not vary with peak velocity. Although monkeys offered less resistance to the initial cycles of applied head motion, the gain and phase of the VOR did not vary for early versus late cycles, suggesting that an efference copy of the motor command to the neck musculature did not alter VOR response dynamics. In addition, VOR dynamics were also probed by applying transient head perturbations with much greater accelerations (peak acceleration >15,000 degrees /s(2)) than have been previously employed. The VOR latency was between 5 and 6 ms, and mean gain was close to unity for two of the three animals tested. A simple linear model well described the VOR responses elicited by sinusoidal and transient head on body rotations. We conclude that the VOR is compensatory over a wide frequency range in monkeys and has similar response dynamics during passive rotation of the head on body as during passive rotation of the whole body in space.     

Correlation of symptoms with occurrence of paroxysmal supraventricular tachycardia or atrial fibrillation: a transtelephonic monitoring study. The Flecainide Supraventricular Tachycardia Study Group.

The purpose of this study was to determine whether symptoms recorded at the time of transtelephonic ECG monitoring (TTEM) correlate with attacks of paroxysmal supraventricular tachycardia (PSVT) or paroxysmal atrial fibrillation (PAF). We studied 113 patients with these arrhythmias who made a total of 3319 TTEM calls during their participation in double-blind, placebo-controlled, crossover, multicenter trials of flecainide therapy. Among 49 patients with PSVT, 62.7% of symptomatic calls were associated with ECG-documented PSVT as compared with 6.8% of asymptomatic calls (p less than 0.001). Similarly, among 69 patients with PAF, 69% of symptomatic calls were associated with ECG-documented PAF compared with 10.6% of asymptomatic calls (p less than 0.001). Both in patients with PSVT and PAF, an attack of PSVT or PAF could be documented by ECG in more than 70% of the calls when patients complained of tachycardia, increased sweating, or dyspnea. The sensitivity of a symptomatic call was 91% for PSVT and 89% for PAF, and it was not influenced by flecainide therapy. However, flecainide therapy was associated with a decrease in the positive predictive value of symptomatic TTEM calls and an increase in false positive TTEM transmissions. We conclude that in patients with symptomatic PSVT or PAF, there is a temporal relationship between symptoms and the occurrence of ECG-documented attacks of PSVT or PAF. However, sole reliance should not be placed on the presence or absence of symptoms as a measure of drug failure or efficacy, and it is important to document the cardiac rhythm by TTEM at the time symptoms are recorded.     

Don't just do something,stand there! The value and art of deliberate clinical inertia

It can be difficult to avoid unnecessary investigations and treatments, which are a form of low‐value care. Yet every intervention in medicine has potential harms, which may outweigh the potential benefits. Deliberate clinical inertia is the art of doing nothing as a positive response. This paper provides suggestions on how to incorporate deliberate clinical inertia into our daily clinical practice, and gives an overview of current initiatives such as ‘Choosing Wisely’ and the ‘Right Care Alliance’. The decision to ‘do nothing’ can be complex due to competing factors, and barriers to implementation are highlighted. Several strategies to promote deliberate clinical inertia are outlined, with an emphasis on shared decision‐making. Preventing medical harm must become one of the pillars of modern health care and the art of not intervening, that is, deliberate clinical inertia, can be a novel patient‐centred quality indicator to promote harm reduction.     

Systemic ventricular function in patients with transposition of the great arteries after atrial repair: a tissue Doppler and conductance catheter study

OBJECTIVES: The aim of this study was to assess the utility of tissue Doppler echocardiography in the setting of repaired transposition of the great arteries when the right ventricle (RV) functions as the systemic ventricle. BACKGROUND: Myocardial acceleration during isovolumic contraction, "isovolumic myocardial acceleration" (IVA), has been validated as a sensitive non-invasive method of assessing RV contractility. Although traditional indexes may be less valid for the abnormal RV, the relative insensitivity of IVA to an abnormal load makes it a potentially powerful clinical tool for the assessment of RV disease. METHODS: We examined 55 controls and 80 patients (mean age 22 years) with transposition, who had undergone atrial repair at age 8 (0.3 to 72) months. A subgroup of 12 underwent cardiac catheterization. The RV systolic function was derived by analysis of pressure-volume relationships and IVA both at rest and during dobutamine stress. In all 80, myocardial velocities were sampled in the RV free wall. RESULTS: During dobutamine (10 microg/kg/min for 10 min), the increase of IVA mirrored the increase in end-systolic elastance (r = 0.69, p < 0.02). In the group as a whole, IVA was reduced compared with the subpulmonary RV and the systemic left ventricle of controls. There was abnormal wall motion in 44 patients, which was associated with reduced IVA. Diastolic myocardial velocities were also abnormal but unrelated to the presence of wall motion abnormalities. CONCLUSIONS: The IVA can accurately assess changes in RV contractile function in patients with an RV as the systemic ventricle. Global long-axis RV function is reduced in patients with transposition, and this is associated with abnormal regional function.     

Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm

Mutational inactivation of the adenomatous polyposis coli (APC) tumor suppressor initiates most hereditary and sporadic colon carcinomas. Although APC protein is located in both the cytoplasm and the nucleus, the protein domains required to maintain a predominantly cytoplasmic localization are unknown. Here, we demonstrate that nuclear export of APC is mediated by two intrinsic, leucine-rich, nuclear export signals (NESs) located near the amino terminus. Each NES was able to induce the nuclear export of a fused carrier protein. Both APC NESs were independently able to interact with the Crm1 nuclear export factor and substitute for the HIV-1 Rev NES to mediate nuclear mRNA export. Both APC NESs functioned within the context of APC sequence: an amino-terminal APC peptide containing both NESs interacted with Crm1 and showed nuclear export in a heterokaryon nucleocytoplasmic shuttling assay. Also, mutation of both APC NESs resulted in the nuclear accumulation of the full-length, approximately 320-kDa APC protein, further establishing that the two intrinsic APC NESs are necessary for APC protein nuclear export. Moreover, endogenous APC accumulated in the nucleus of cells treated with the Crm1-specific nuclear export inhibitor leptomycin B. Together, these data indicate that APC is a nucleocytoplasmic shuttle protein whose predominantly cytoplasmic localization requires NES function and suggests that APC may be important for signaling between the nuclear and cytoplasmic compartments of epithelial cells.