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Biomedical subjects

B Weinberg

Publications and source records attributed to B Weinberg.

At least 19 recordsLinked to original sources

NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease.

Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between amyloid and tau aggregates is of intense interest, but mouse models have yet to reveal a direct interrelationship. We now show that NO may be a key factor that connects amyloid and tau pathologies. Genetic removal of NO synthase 2 in mice expressing mutated amyloid precursor protein results in pathological hyperphosphorylation of mouse tau, its redistribution to the somatodendritic compartment in cortical and hippocampal neurons, and aggregate formation. Lack of NO synthase 2 in the amyloid precursor protein Swedish mutant mouse increased insoluble beta-amyloid peptide levels, neuronal degeneration, caspase-3 activation, and tau cleavage, suggesting that NO acts at a junction point between beta-amyloid peptides, caspase activation, and tau aggregation.

Alzheimer Disease↗

Local carboplatin delivery and tissue distribution in livers after radiofrequency ablation.

This study investigated the local drug pharmacokinetics of intralesional drug delivery after radiofrequency ablation of the liver. We hypothesized that the tissue architecture damaged by the ablation process facilitates the drug penetration in the liver and potentially enlarges the therapeutic margin in the local treatment of cancer. The delivery rate and tissue distribution of carboplatin, an anticancer agent, released from poly(D,L-lactide-co-glycolide) implants into rat livers after radiofrequency ablation were quantified by atomic absorption spectroscopy. Results showed that carboplatin clearance through blood perfusion was significantly slower in the ablated livers, leading to a more extensive tissue retention and distribution of the drug. The concentration of Pt at the implant-tissue interface ranged from 234 to 1440 microg Pt/(g liver) in the ablated livers over 144 h versus 56 to 177 microg Pt/(g liver) in the normal tissue. The maximum penetration distance at which Pt level reached above 6 microg/g (calculated based on a reported IC90 value for carboplatin) was 8-10 mm and 4-6 mm in ablated and normal liver, respectively. Histological analysis of the necrotic lesions showed widespread destruction of tissue structure and vasculature, supporting the initial hypothesis. This study demonstrated that intralesional drug delivery could provide a sustained, elevated concentration of anticancer drug at the ablation boundary that has the potential to eliminate residual cancer cells surviving radiofrequency ablation.

Animals↗

Sonographic sign of intermittent dilatation of the renal collecting system in 10 patients with vesicoureteral reflux.

PURPOSE: Renal sonography is an accepted primary imaging modality for evaluating the pediatric urinary tract. We report a new sonographic finding associated with vesicoureteral reflux (VUR). METHODS: Ten patients underwent sonographic evaluation of the kidneys and were noted to have intermittent renal collecting system dilatation that expanded and contracted during real-time scanning. These patients were further evaluated with voiding cystourethrography. RESULTS: All 10 patients were proven to have VUR on the side of the sonographic abnormality. Four patients had bilateral VUR for a total of 14 refluxing renal units. Of these 14 renal units, 1 was sonographically normal. Five of the 14 renal units had grade V VUR that required surgical reimplantation of the ureter. CONCLUSIONS: This new finding of intermittent renal collecting system dilatation may become an important predictor of VUR. The finding warrants further evaluation even when detected in patients not suspected of having VUR who are undergoing renal sonography for other reasons.

Child, Preschool↗

Characteristics of voicing source waveforms produced by esophageal and tracheoesophageal speakers.

Voicing source waveforms produced by 10 laryngectomized esophageal speakers, 12 laryngectomized tracheoesophageal speakers, and 10 age-matched, normal male speakers were obtained by inversely filtering flow functions recorded with a circumferentially vented mask. The data from these speakers was used to evaluate differences in source signal properties on a group basis. In a second analysis source signals produced by a single laryngectomized individual, capable of producing esophageal and tracheoesophageal speech in a highly proficient manner, were analyzed and compared. The overall results of this project provide an initial and novel description of voicing source signals produced by esophageal and tracheoesophageal speakers. The characteristics of these signals appear to be highly variable, particularly in comparison with the homogeneous pattern of source waves produced by age-matched, normal speakers. This initial description of voicing source signals produced by alaryngeal speakers is generally supportive of the hypothesis of differences in source properties among normal, esophageal, and tracheoesophageal voices.

Humans↗

Minimizing the effect of period determination on the computation of amplitude perturbation in voice.

Current methods of computing amplitude perturbation present in human voices depend upon being able to accurately determine fundamental period. In this paper, two methods of estimating the amplitude perturbation present in human voices, which do not depend on accurate determination of the boundaries between fundamental periods, are described. In both of these methods, amplitude perturbation is computed as the variance of an ensemble of periods calculated after these periods have been aligned in time. In one method, time alignment is accomplished using zero-phase transformation. In the second method, an unconstrained dynamic programming procedure is used. The accuracy of estimating amplitude perturbation by these two methods is evaluated using synthetic and natural voice signals and is also compared with an estimation using zero-padding based time alignment. The unconstrained dynamic programming method is shown to provide accurate estimation of voice amplitude perturbation over a variety of signal conditions.

Female↗

Enhancement of female esophageal and tracheoesophageal speech.

Qi [J. Acoust. Soc. Am. 88, 1228-1235 (1990)] has demonstrated that (1) linear predictive (LP) methods can be used to separate vocal tract transfer functions from source functions of vowels produced by alaryngeal talkers and that (2) vowels synthesized with reconstructed transfer functions and totally synthetic voicing excitation sources have improved source-related properties over those present in the original vowels. Here, an extension of this work which is directed to the general goal of developing systems (devices) to enhance the quality of alaryngeal speech is reported. The specific goal of the present project was to determine whether speech, i.e., words spoken by female esophageal and tracheoesophageal talkers, could be enhanced by means of LP-based analysis and synthesis methods. Words spoken by four female alaryngeal talkers were analyzed and synthesized. A perceptual evaluation was completed to permit the quality of the synthetic and the original words to be compared. Listeners generally preferred to listen to the synthesized words, indicating that alaryngeal speech enhancement was accomplished.

Female↗

A homomorphic method for measuring secondary amplitude modulation.

A homomorphic processing, software implemented method for measuring secondary amplitude modulation (AM) is described. The accuracy of measurement of this method was tested on a series of synthetically produced AM and vowel signals. The homomorphic method provided highly accurate measurement of modulation frequency and modulation index.

Humans↗

Serum and ascitic fluid levels of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in patients with ovarian epithelial cancer.

BACKGROUND: Recent studies have shown that multiple cytokines are secreted by ovarian epithelial cancer cells. Previous studies have shown that the cancer cell lines secrete macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-6 (IL-6), and transforming growth factor-alpha (TGF-alpha). Concomitantly, the serum levels of one of the growth factors (M-CSF) was found to be significantly elevated in patients with primary ovarian cancer and in second-look patients. The authors evaluated the serum levels of IL-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in patients with primary ovarian epithelial cancer. These levels were then compared with cytokine concentration found in normal peritoneal fluid. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of cytokines in normal peritoneal fluid, ascites, and serum. RESULTS: In serum, TNF-alpha and IL-6 were significantly increased in primary ovarian cancer patients when compared with control subjects (P < 0.0001 for both cytokines). TNF-alpha and IL-6 were also significantly higher than the levels found in second-look patients (P < 0.007 for TNF-alpha, and P = 0.0002 for IL-6). The levels of IL-1 alpha and beta were not elevated in ovarian cancer. TNF-alpha in the ascites was higher when compared with normal peritoneal fluid and was statistically significantly different when a cut-off point between 71-110 pg was selected (P < 0.005). The levels of IL-6 in ascites from patients with primary ovarian cancer also showed a marked increase (P < 0.0001) when compared with peritoneal fluid from control subjects. CONCLUSIONS: Levels of IL-1, IL-6, and TNF-alpha were determined in normal peritoneal fluid, ovarian malignant ascites, normal serum, and serum from patients with ovarian cancer. This study showed that the patients with ovarian cancer have elevated levels of IL-6 and TNF-alpha in serum and ascitic fluid. A larger study would help in evaluating the potential use of cytokines as tumor markers in ovarian cancer.

Ascitic Fluid↗

The apical oblique view of the clavicle: its usefulness in neonatal and childhood trauma.

We analyzed clavicular radiographs of 26 patients with a history of trauma. The apical oblique projection of the clavicle was obtained with the injured side of the patient angled 45 degrees towards the X-ray tube and a 20 degrees cephalad angulation of the X-ray beam. This view proved to be more informative than the routine apical anteroposterior projection. It is especially effective in detecting nondisplaced fractures of the middle third of the clavicle in neonates and children. To verify our findings, we obtained apical anteroposterior and oblique radiographs of a specimen adult clavicle. On the oblique view with 20 degrees cephalad angulation of the X-ray beam, the measurements of the projected lengths of the anatomical specimen, especially those of the middle portion of the clavicle, were very close to the corresponding anatomical lengths.

Birth Injuries↗

Spectral slope of vowels produced by tracheoesophageal speakers.

Spectra of vowels were analyzed to determine whether differences exist between the spectral slope of vowels produced by tracheoesophageal (TE) speakers and normal speakers and, if so, to quantify such differences. The linear predictive autocorrelation method was used to calculate smoothed spectra and the spectra were normalized with respect to a low frequency component. Comparisons between normalized spectral energy within a selected high frequency range revealed that energy within this frequency range for vowels produced by TE speakers was significantly higher than that produced by normal speakers. A least-square distance matching procedure was used to quantify speaker group differences in the spectral slope of vowels. Average spectra of vowels produced by the normal speakers could be matched to average spectra of vowels produced by the TE speakers by decreasing the spectral slope of their vowels by 2-3 dB/octave.

Adult↗

Low-frequency energy deficit in electrolaryngeal speech.

The present exploratory project was undertaken (a) to determine the relative strength of low-frequency energy in the output of one widely used electronic artificial larynx (Servox) and (b) to assess the relative strength of low-frequency energy in vowels produced by users of this type of artificial larynx. We hypothesized that the outputs of electronic artificial larynges and the vowels produced by laryngectomized users of these devices would be characterized by significant deficits in low-frequency energy level. Five users of electronic larynges and 10 normal speakers (5 female and 5 male) provided the speech samples. Results of spectral analyses indicated that there was a significant deficit in low-frequency energy both in the acoustic signals generated by a Servox electronic larynx and in vowels produced by laryngectomized users of this type of electronic larynx. Based on these findings, a second order filter was designed and implemented digitally to compensate for the observed deficit in low-frequency energy. A perceptual experiment was completed to evaluate the effect of low-frequency enhancement on perceived speech quality. Ninety-eight percent (+/- 2%) of the responses of listeners indicated that low-frequency enhanced speech samples had better vocal quality or were more pleasant to listen to than the original speech samples. We conclude that consideration for enhancing low-frequency characteristics is warranted in the design of improved prosthetic devices for alaryngeal speakers.

Aged↗

Strategies to manage the post-MI patient with ventricular arrhythmias.

The occurrence of late ventricular arrhythmias after acute myocardial infarction is common. The available data do not support the treatment of asymptomatic premature ventricular complexes or asymptomatic non-sustained ventricular tachycardia after acute myocardial infarction. Signal-averaged electrocardiograms, perhaps in combination with Holter recording and measurements of left ventricular function show promise as potential markers of risk for subsequent sudden death or sustained ventricular tachycardia. Nevertheless, the appropriate treatment of any high-risk but asymptomatic subset of patients has not been established. Patients experiencing sustained ventricular tachycardia after acute myocardial infarction and survivors of late ventricular fibrillation are at high risk of early cardiac mortality and require aggressive treatment which may consist of serial electrophysiologic testing to evaluate drug therapy, arrhythmia surgery, or placement of an automatic implantable cardioverter defibrillator.

Arrhythmias, Cardiac↗