Restoration of 3D vestibular sensation in rhesus monkeys using a multichannel vestibular prosthesis

Profound bilateral loss of vestibular hair cell function can cause chronically disabling loss of balance and inability to maintain stable vision during head and body movements. We have previously shown that chinchillas rendered bilaterally vestibular-deficient via intratympanic administration of the ototoxic antibiotic gentamicin regain a more nearly normal 3-dimensional vestibulo-ocular reflex (3D VOR) when head motion information sensed by a head-mounted multichannel vestibular prosthesis (MVP) is encoded via rate-modulated pulsatile stimulation of vestibular nerve branches. Despite significant improvement versus the unaided condition, animals still exhibited some 3D VOR misalignment (i.e., the 3D axis of eye movement responses did not precisely align with the axis of head rotation), presumably due to current spread between a given ampullary nerve's stimulating electrode(s) and afferent fibers in non-targeted branches of the vestibular nerve. Assuming that effects of current spread depend on relative orientation and separation between nerve branches, anatomic differences between chinchilla and human labyrinths may limit the extent to which results in chinchillas accurately predict MVP performance in humans. In this report, we describe the MVP-evoked 3D VOR measured in alert rhesus monkeys, which have labyrinths that are larger than chinchillas and temporal bone anatomy more similar to humans. Electrodes were implanted in five monkeys treated with intratympanic gentamicin to bilaterally ablate vestibular hair cell mechanosensitivity. Eye movements mediated by the 3D VOR were recorded during passive sinusoidal (0.2-5?Hz, peak 50°/s) and acceleration-step (1000°/s(2) to 150°/s) whole-body rotations in darkness about each semicircular canal axis. During constant 100?pulse/s stimulation (i.e., MVP powered ON but set to stimulate each ampullary nerve at a constant mean baseline rate not modulated by head motion), 3D VOR responses to head rotation exhibited profoundly low gain [(mean eye velocity amplitude)/(mean head velocity amplitude)?相似文献   

Magnetic resonance imaging (MRI) assessment of vocal fold medialization surgery

Historically, clinicians have used subjective assessment and perceptual judgments, supplemented with acoustic measures, aerodynamic studies, and videostroboscopy, to determine the effects of phonosurgery. When phonosurgical results are poor, magnetic resonance imaging (MRI) can be useful in determining how the surgical modifications contributed to the anatomical and functional status of the vocal folds. The authors present examples of MRI following vocal fold medialization by injection, thyroplasty, and arytenoid adduction. Findings reveal that the superior contrast resolution of MRI can precisely identify placement and persistence of injected implants and is particularly helpful in showing effects of the size and shape of alloplastic prostheses on vocal fold displacement. Such information is useful in troubleshooting suboptimal results and in planning revision thyroplasty by defining modification in the design of prostheses and the placement of cartilaginous windows in medialization thyroplasty. MRI can also aid in confirming indications for and limitations of certain procedures.     

Impact of muscarinic agonists for successful therapy of Alzheimer's disease

The M1 muscarinic agonists AF102B, AF150(S) & AF267B--i) restored cognitive impairments in several animal models for AD with an excellent safety margin; ii) elevated alpha-APPs levels; iii) attenuated vicious cycles induced by A beta, and inhibited A beta- and oxidative stress-induced apoptosis; and iv) decreased tau hyperphosphorylation. AF150(S) and AF267B were more effectve than rivastigmine and nicotine in restoring memory impairments in mice with small hippocampi. In apolipoprotein E-knockout mice, AF150(S) restored cognitive impairments and cholinergic hypofunction and decreased tau hyperphosphorylation. In aged microcebes, AF150(S) restored cognitive and behavioral impairments and decreased tau hyperphosphorylation, paired helical filaments and astrogliosis. In rabbits, AF267B & AF150(S) decreased CSF A beta(1-42 & 1-40), while AF102B reduced A beta(1-40). Finally AF102B decreased CSF A beta(total) in AD patients. Taken together, M1 agonists may represent a unique therapy in AD due to their beneficial effects on three major hallmarks of AD--cholinergic hypofunction, A beta and tau protein hyperphosphorylation.     

Development and evaluation of an enzyme-linked immunoassay for the prostate: specific antigen utilizing two monoclonal antibodies

Summary PSA is an important tumor-marker for prostatic cancer disease. We developed a sensitive, simple and inexpensive Sandwich ELISA for PSA with two monoclonal antibodies. The precision and reliability of the assay are reflected in the low inter-and intraassay coefficient of variation. PSA was not detectable in sera from normal females (n=50). Sera from males with different serum levels of PSA (normal males, patients with prostate hypertrophy, prostate cancer patients, n=79) and 15 prostate cancer patients treated with Zoladex were measured by our ELISA and by a commercially available RIA. The correlation coefficient between these both testsystems was close to 1 (r=0.97).     

Diagnostic tools for the study of vascular cognitive dysfunction in hypertension and antihypertensive drug research

Arterial hypertension is one of the main risk factors for cerebrovascular diseases, and antihypertensive treatment has significantly reduced their associated mortality. However, morbidity has not been reduced to a similar extent and a still increasing number of patients suffers from recurring strokes and from the disabling consequences of cerebrovascular diseases and develops progressive cognitive impairment. It is still debated to what extent antihypertensive treatment may prevent the development of cognitive dysfunction, due to the lack of a focused approach to vascular cognitive impairment, to the lack of a systematic study of the early phases of dementia, and to the use of diagnostic tests that are not sensitive and specific for a slow onset clinical condition, such as dementia. The aim of the present expert consensus report is to enlist the diagnostic tools that are currently available to assess mild cognitive impairment (MCI) and early dementia and that are sensitive and specific enough to be used in observational, longitudinal, and interventional clinical research studies, aiming to investigate the impact of antihypertensive drugs on vascular dementia (VD).     

Could steroids mask the diagnosis of cerebrotendinous xanthomatosis?

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis, caused by impaired hydroxylation of cholesterol side chains due to deficiency of the mitochondrial enzyme sterol 27-hydroxylase (CYP27A1), leading to accumulation of cholestanol and cholesterol in brain and other tissues. Elevated plasma cholestanol serves as a key marker for the clinical diagnosis of CTX. In the present report we describe a young man with CTX who was on high dose steroids for a misdiagnosed chronic inflammatory demyelinating polyneuropathy (CIDP) and had normal level of serum cholestanol. When steroids were discontinued, markedly elevated serum cholestanol was measured concomitant with marked clinical worsening. This observation may imply that steroids can lower plasma cholestanol, possibly by directly inducing residual CYP27A1 activity or by inducing alternative pathways for cholestanol elimination.     

Management of Acute Bleeding after Laparoscopic Roux-en-Y Gastric Bypass

Background: The authors reviewed the incidence of hemorrhage after laparoscopic Roux-en-Y gastric bypass (LRYGBP). The purpose of this study was to determine the incidence of this complication and to evaluate various treatment options. Material and Methods: The records for 450 consecutive patients who had undergone LRYGBP over a 30-month period, were retrospectively reviewed. In all patients, the abdominal cavity had been drained with 2 19-Fr closed suction drains. The charts of patients who had developed an intraluminal or an intraabdominal bleed were chosen for further review. Results: 20 patients (4.4%) developed an acute postoperative hemorrhage. The bleeding was intraluminal in 12 cases (60%), manifested by a drop in hematocrit, tachycardia and melena. The other 8 patients (40%) developed intra-abdominal hemorrhage, confirmed by large bloody output from the drains. 3 patients (15%) with intraluminal bleeding were unstable and required a reoperation. All others were successfully treated with observation, and 15 patients (75%) required blood transfusions. Conclusions: The diagnosis and treatment of acute intraluminal bleeding after LRYGBP represents a surgical dilemma, mainly due to the inaccessibility of the bypassed stomach and the jejuno-jejunostomy, as well as the risks associated with early postoperative endoscopy. The presence of large intra-abdominal drains allows for bleeding site localization (intraluminal vs intraabdominal) and for more accurate monitoring of the bleeding rate. Most cases respond to conservative therapy. Failure of conservative management of intraluminal bleeding, however, is more problematic and may require operative intervention. A treatment algorithm is proposed.