Citations

Background and Purpose— The prognostic significance of subarachnoid extension of intracerebral hemorrhage was determined in the INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2) study. Methods— INTERACT2 was an open randomized controlled trial of early intensive compared with guideline-recommended blood pressure lowering in patients with elevated systolic blood pressure within 6 hours of intracerebral hemorrhage. Independent predictors of death or major disability (scores 3–6 on the modified Rankin Scale) at 90 days were analyzed in logistic regression models. Results— Of 2582 participants, 192 (7%) had subarachnoid extension, which was associated with larger hematoma volumes ( P <0.0001) and higher National Institute of Health Stroke Scale score ( P <0.0001). Subarachnoid extension predicted death or major disability at 90 days (71% versus 53%; unadjusted odds ratio, 2.25; 95% confidence interval, 1.63–3.10; P <0.0001). The association remained significant after adjusting for age, region, lipid-lowering therapy, systolic blood pressure, glucose, location of hematoma, intraventricular extension, and randomized treatment (odds ratio, 2.17; 95% confidence interval, 1.50–3.14; P <0.0001), but not after further adjustment for baseline hematoma volume ( P =0.62). Conclusions— Subarachnoid extension of intracerebral hemorrhage is associated with poor prognosis, which is determined by a larger volume of the underlying intraparenchymal hematoma. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Vibro-acoustography is an imaging technique that maps the acoustic response of an object to a localized harmonic radiation force. This force is generated by two interfering continuous-wave ultrasound beams at slightly different frequencies f1 and f2. The system point-spread function (PSF) is related to the radiation force on a point-target. Imaging artifacts depend on the PSF sidelobes, which can be reduced by mismatching the sidelobes of each ultrasound beam. Here, we propose a beamforming approach based on an 8-element sector transducer with consecutive elements alternately driven at f1 and f2. The transducer generates two ultrasound beams skewed by 22.5° with respect to each other. The system PSF is analytically derived. The theory is validated by experiments using a small steel sphere (radius =0.2 mm) as a point-target. A laser vibrometer is used to measure the vibration of the sphere and evaluate the PSF of the system. Theoretically, the PSF sidelobes are under −15.8 dB in eight spots circularly distributed and separated by 22.5°, which agrees with the experimental results. Simulation shows that with 16 elements sidelobes are under −35.2 dB. In conclusion, sector transducers for vibro-acoustography may have lower sidelobes as the number of array elements is increased. [Work supported by Grant Nos. EB00535-01, EB2640, and IMG0100744.]

Background We investigated whether disease location influences survival in patients with peripheral arterial disease. Methods and Results Patients (n=12 731; mean age, 67.5±12.7 years; 57.4% male) who underwent outpatient noninvasive lower extremity arterial evaluation were followed up for 5.9±3.1 years for all‐cause mortality. Peripheral arterial disease (n=8930) was defined as a resting or postexercise ankle‐brachial index ( ABI ) ≤0.90, and normal ABI (n=3 801) was defined as a resting and postexercise ABI of 1.00 to 1.30. Presence or absence of disease at the proximal location or distal location was determined on the basis of D oppler signals in leg arteries; 42% had no PD or DD , 45% had proximal (14% postexercise PD only), 30% had distal disease, 17% had both proximal and distal disease, 28% had proximal only and 14% had distal only. We performed multivariable logistic regression to identify factors associated with disease location, and C ox proportional hazard regression to assess the respective effects of proximal or distal disease on survival. Older age, male sex, diabetes, heart failure, and critical limb ischemia were associated with distal disease, whereas female sex, smoking, hypertension, dyslipidemia, coronary heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and critical limb ischemia were associated with proximal disease. Over a mean follow‐up of 5.9±3.1 years, 3039 patients (23.9%) died. After adjustment for potential confounders, the hazard ratios ( HR s) of death associated with PD only and DD only were 1.3 (1.3 to 1.4) and 1.5 (1.4 to 1.6), respectively. After additional adjustment for resting ABI , there was no significant association between proximal disease and death, whereas the association of distal disease with death remained significant ( HR , 1.2; 95% CI , 1.1 to 1.3). Conclusions In patients with peripheral arterial disease, proximal and distal disease locations were associated with distinctive risk factor and comorbidity profiles. Distal disease was associated with worse survival even after adjustment for risk factors, comorbidities, and resting ABI .

GH deficiency is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, therapy with GH and/or IGF-I has not shown benefit. To gain a better understanding of the role of GH secretion in ALS pathogenesis, we assessed endogenous GH secretion in wild-type and hSOD1G93A mice throughout the course of ALS disease. Male wild-type and hSOD1G93A mice were studied at the presymptomatic, onset, and end stages of disease. To assess the pathological features of disease, we measured motor neuron number and neuromuscular innervation. We report that GH secretion profile varies at different stages of disease progression in hSOD1G93A mice; compared with age-matched controls, GH secretion is unchanged prior to the onset of disease symptoms, elevated at the onset of disease symptoms, and reduced at the end stage of disease. In hSOD1G93A mice at the onset of disease, GH secretion is positively correlated with the percentage of neuromuscular innervation but not with motor neuron number. Moreover, this occurs in parallel with an elevation in the expression of muscle IGF-I relative to controls. Our data imply that increased GH secretion at symptom onset may be an endogenous endocrine response to increase the local production of muscle IGF-I to stimulate reinnervation of muscle, but that in the latter stages of disease this response no longer occurs.

Elasticity imaging methods have been used to study tissue mechanical properties and have demonstrated that tissue elasticity changes with disease state. Quantitative mechanical properties can be measured in a model independent manner if both shear wave speed and attenuation are known. However, measuring shear wave speed attenuation is challenging in the field of elasticity imaging. Typically, only shear wave speed is measured and rheological models, such as Kelvin-Voigt, Maxwell and Standard Linear Solid, are used to solve for shear viscoelastic complex modulus. Acoustic radiation force has been used to study quasi-static viscoelastic properties of tissue during creep and relaxation conditions, however, as with shear wave propagation methods, a rheological model needs to be fit to the creep or relaxation experimental data to solve for viscoelastic parameters. This paper presents a method to quantify viscoelastic properties in a model-independent way by estimating complex shear elastic modulus over a wide frequency range using time-dependent creep response induced by acoustic radiation force. The acoustic radiation force induced creep (RFIC) method uses a conversion formula that is the analytic solution of the constitutive equation relating time dependent stress and time dependent strain. The RFIC method in combination with shear wave propagation is used to measure the complex shear modulus so that knowledge of the applied radiation force magnitude is not necessary. Numerical simulation of creep strain and compliance using the Kelvin-Voigt model shown that the conversion formula is sensitive to sampling frequency, the first reliable measure in time and the long term viscosity approximation. Experimental data are obtained in homogeneous tissue mimicking phantoms and excised swine kidneys.

Background. Graft pretreatment to limit postoperative damage has the advantage of overcoming a current issue in liver transplantation (LT). The strategic potential of graft pretreatmentin vivoby a specific agonist forγ-aminobutyric acid receptor (GABAR) was investigated in the rat LT model with a small-for-size graft (SFSG).Methods. Recipient rats were divided into three groups according to donor treatments and recipient surgeries: (i) saline and laparotomy, (ii) saline and split orthotopic liver transplantation (SOLT) with 40%-SFSG, and (iii) GABAR agonist and SOLT with 40%-SFSG. Survival was evaluated. Blood and liver samples were collected 6 h after surgery. Immunohistological assessment for apoptotic induction and western blotting for 4-hydroxynonenal, ataxia-telangiectasia mutated kinase (ATM), histone H2AX, phosphatidylinositol-3 kinase (PI3K), Akt, and free radical scavenging enzymes were performed.Results. Pretreatment by GABAR showed improvement in survival, histopathological assessment, and biochemical tests. Apoptotic induction and oxidative stress were observed after SOLT with an SFSG, and this damage was limited by GABAR regulation. GABAR regulation appeared to reduce DNA damage via the ATM/H2AX pathway and to promote cell survival via the PI3K/Akt pathway.Conclusions. Pretreatmentin vivoby GABAR regulation improves graft damage after SOLT with an SFSG. This strategy may be advantageous in LT.

Current methodology to monitor pulsatile LH release in mice is limited by inadequate assay sensitivity, resulting in the need for collection of large blood volumes. Thus, assessment of pulsatile LH secretion in mice remains highly challenging, and observations are limited to adult mice. To address this, we developed a highly sensitive ELISA for assessment of mouse LH concentrations in small fractions of whole blood. We demonstrate that this assay is capable of reliably detecting LH down to a theoretical limit of 0.117 ng/mL in a 2-μL fraction of whole blood. Using an established frequent blood collection procedure, we validated the accuracy of this method by determining the pulsatile LH secretion in early-adult (10 weeks old) C57BL6/J male mice. Data demonstrate regular pulsatile release of LH, with peaks in LH secretion rarely exceeding 3 ng/mL. Moreover, assessment of LH release in Gpr54 knockout mice demonstrates the lack of pulsatile LH release after the loss of kisspeptin-mediated pubertal maturation. We next determined age-associated changes in pulsatile LH secretion by assessment of LH secretion in prepubertal (28 days old) C57BL6/J male mice and repeated assessment in the same mice in adulthood (120 days old). Data demonstrate that the rise in total LH secretion in mice after pubertal maturation occurs along with an overall rise in the pulsatile LH secretion rate. This was coupled with a significant increase in the number of LH secretory events (number of pulses). In addition, we observed a decrease in the clearance (increased half-life) and a decrease in the regularity (approximate entropy) of LH release. This method will be of wide general utility within the field of reproductive biology.