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Biomedical subjects

R R Price

Publications and source records attributed to R R Price.

At least 19 recordsLinked to original sources

Emulsification preparation of chitosan-urethane microbeads in the presence of a water-soluble blocked diisocyanate, containing furanone homosyrine lactone bacterial inhibitors.

Chitosan is an abundant naturally occurring biopolymer that is biocompatible, of low toxicity and is well suited as a carrier for a range of active agents. Restrictions imposed by this biopolymers unique solubility requirements make if difficult to process. One approach to an internal setting system is to employ the water-soluble blocked isocyanate hexamethylene-1,6-di(aminocarboxysulphonate) (HDACS) in order to cross-link the chitosan and form microspheres in situ utilizing simple emulsion systems. Chitothane microspheres are capable of delivering active agents at controlled release rates and offers a viable alternative to external set methodologies utilizing aldehydes or similar cross-linking agents.

Biocompatible Materials↗

Laparoscopy for appendicitis and cholelithiasis during pregnancy: a new standard of care.

BACKGROUND: Subsequent to a report from the authors' institution, the laparoscopic management of symptomatic cholelithiasis and appendicitis during pregnancy has become the standard of care at LDS Hospital using institutional guidelines. For comparison with previous outcomes described by the authors, 59 additional laparoscopic cases are reported. METHODS: Medical records of all pregnant patients at LDS Hospital who underwent open or laparoscopic cholecystectomy or appendectomy between 1998 and 2002 were reviewed. The outcomes were compared with the authors' previous data. RESULTS: The laparoscopic management of symptomatic cholelithiasis and appendicitis during pregnancy increased from 54% to 97%. No significant differences in preterm delivery rates, birth weights, or 5-min Apgar scores were found between the two periods. No birth defects or uterine injuries occurred. CONCLUSIONS: With the use of the authors' guidelines, laparoscopy has become the standard of care for managing symptomatic cholelithiasis and appendicitis during pregnancy at LDS Hospital without significant increase in morbidity or mortality.

Adult↗

In vivo and in vitro proton NMR spectroscopic studies of thiamine-deficient rat brains.

Thiamine deficiency (TD) in rats produces lesions similar to those found in humans with Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 24) were deprived of thiamine in a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist pyrithiamine hydrobromide for 12 days (0.5 mg/kg). In rats with TD, significant changes were observed in the choline peak (reduction and dose-dependent recovery after thiamine replenishment), which was confirmed by the extraction study. Changes were mainly due to the reduction in glycerophosphorylcholine (GPC), suggesting that a reduction in GPC may be relevant to the primary biochemical lesion in TD. These data are compatible with the hypothesis that a decrease in choline compounds is the cause of the biochemical abnormalities that precede neuroanatomic damage characteristic of Wernicke's encephalopathy.

Animals↗

Cortical activation during Braille reading is influenced by early visual experience in subjects with severe visual disability: a correlational fMRI study.

Functional magnetic resonance imaging was performed on blind adults resting and reading Braille. The strongest activation was found in primary somatic sensory/motor cortex on both cortical hemispheres. Additional foci of activation were situated in the parietal, temporal, and occipital lobes where visual information is processed in sighted persons. The regions were differentiated most in the correlation of their time courses of activation with resting and reading. Differences in magnitude and expanse of activation were substantially less significant. Among the traditionally visual areas, the strength of correlation was greatest in posterior parietal cortex and moderate in occipitotemporal, lateral occipital, and primary visual cortex. It was low in secondary visual cortex as well as in dorsal and ventral inferior temporal cortex and posterior middle temporal cortex. Visual experience increased the strength of correlation in all regions except dorsal inferior temporal and posterior parietal cortex. The greatest statistically significant increase, i.e., approximately 30%, was in ventral inferior temporal and posterior middle temporal cortex. In these regions, words are analyzed semantically, which may be facilitated by visual experience. In contrast, visual experience resulted in a slight, insignificant diminution of the strength of correlation in dorsal inferior temporal cortex where language is analyzed phonetically. These findings affirm that posterior temporal regions are engaged in the processing of written language. Moreover, they suggest that this function is modified by early visual experience. Furthermore, visual experience significantly strengthened the correlation of activation and Braille reading in occipital regions traditionally involved in the processing of visual features and object recognition suggesting a role for visual imagery.

Adult↗

Comparison of functional MRI image realignment tools using a computer-generated phantom.

This study discusses the development of a computer-generated phantom to compare the effects of image realignment programs on functional MRI (fMRI) pixel activation. The phantom is a whole-head MRI volume with added random noise, activation, and motion. It allows simulation of realistic head motions with controlled areas of activation. Without motion, the phantom shows the effects of realignment on motion-free data sets. Prior to realignment, the phantom illustrates some activation corruption due to motion. Finally, three widely used realignment packages are examined. The results showed that the most accurate algorithms are able to increase specificity through accurate realignment while maintaining sensitivity through effective resampling techniques. In fact, accurate realignment alone is not a powerful indicator of the most effective algorithm in terms of true activation.

Adult↗

A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.

Bile acids repress the transcription of cytochrome P450 7A1 (CYP7A1), which catalyzes the rate-limiting step in bile acid biosynthesis. Although bile acids activate the farnesoid X receptor (FXR), the mechanism underlying bile acid-mediated repression of CYP7A1 remained unclear. We have used a potent, nonsteroidal FXR ligand to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain. SHP-1 represses expression of CYP7A1 by inhibiting the activity of liver receptor homolog 1 (LRH-1), an orphan nuclear receptor that is known to regulate CYP7A1 expression positively. This bile acid-activated regulatory cascade provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis.

Animals↗

The laparoscopic management of appendicitis and cholelithiasis during pregnancy.

BACKGROUND: Laparoscopic management of appendicitis and symptomatic cholelithiasis during pregnancy remains controversial. We report the single largest series of laparoscopic cholecystectomies and appendectomies during pregnancy. METHODS: Medical records of all pregnant patients who underwent open or laparoscopic management of appendicitis/cholelithiasis at LDS Hospital from 1990 to 1998 were reviewed. RESULTS: Eighteen open appendectomies (OA) and 13 open cholecystectomies (OC) were performed. Forty-five laparoscopic cholecystectomies (LC) and 22 laparoscopic appendectomies (LA) were performed without birth defects, fetal loss or uterine injury. Preterm delivery rates (PTD) in the LA and OA groups were similar (15.8% versus 11.8%, P>0.9). The PTD rate in the LC group was not significantly different than in the OC group (11.9% versus 10.0%, P>0.9). Neither birth weights nor Apgar scores were significantly different across groups. CONCLUSIONS: Laparoscopic management of appendicitis and symptomatic cholelithiasis during pregnancy can be performed with minimal fetal and maternal morbidity when accepted management guidelines are followed.

Adult↗

Molecular pharmacology of human alpha1-adrenergic receptors: unique features of the alpha 1a-subtype.

alpha1-Adrenergic receptors (alpha1ARs) are G protein-coupled receptors important in the dynamic component of benign prostatic hyperplasia. alpha1ARs stimulate predominantly phospholipase C-beta, resulting in mobilization of calcium from intracellular stores and, ultimately, smooth muscle contraction. cDNAs encoding three human alpha1ARs (alpha1a, alpha1b, alpha1d) have been cloned, expressed stably in cells, and characterized pharmacologically. Extensive species heterogeneity in tissue distribution emphasizes the importance of studying alpha1ARs in human tissues. Because of the important role of alpha1aARs in mediating prostate smooth muscle contraction, this current review describes alpha1a carboxyl terminal splice variants, examines alpha1AR subtype distribution in various tissues and the role of the putative alpha1LAR in human prostate, provides a brief discussion regarding regulation of this receptor by agonist, and finally discusses implications of distinct alpha1AR subtype distribution in human bladder compared with prostate.

Adrenergic alpha-Antagonists↗

Alpha1-adrenergic receptor subtypes in human detrusor.

PURPOSE: To identify and quantitate alpha1-adrenergic receptor (alpha1AR) subtype expression in human detrusor. MATERIALS AND METHODS: Initial studies to determine alpha1AR expression in human detrusor were performed using saturation binding with [125I]HEAT. Once the presence of alpha1ARs was documented, subtype (alpha1a, alpha1b, alpha1d) expression at the mRNA level (and comparison with rat) was determined with RNase protection assays (human detrusor) and RT-PCR (human detrusor, rat whole bladder). Competition binding analysis with the alpha1dAR-selective ligand BMY7378 was used to measure alpha1AR subtype expression at a protein level in human detrusor. RESULTS: Alpha1AR expression in human detrusor was low but reproducible (6.3 +/- 1.0 fmol./mg. total protein). RNase protection assays performed on total RNA extracted from human detrusor revealed the following alpha1AR subtype expression: alpha1d (66%) > alpha1a (34%), and no alpha1b. RT-PCR confirmed alpha1AR subtype mRNA distribution in human detrusor with alpha1d (approximately 60-70%) > alpha1a (approximately 30-40%), and a lack of alpha1b mRNA. Rat whole bladder expressed different alpha1AR subtype mRNA than human detrusor, with alpha1a approximately alpha1b approximately alpha1d. The presence of alpha1d > alpha1a expression in human detrusor was confirmed at a protein level by competition analysis utilizing BMY7378 which revealed a two-site fit, with Ki and high affinity binding (66%) consistent with the alpha1dAR subtype. CONCLUSIONS: Human detrusor contained two alpha1AR subtypes (alpha1d > alpha1a), a finding that is different from rat, another commonly used animal model. Since non-subtype selective alpha1AR antagonists ameliorate irritative bladder symptoms (in men and women with/without outlet obstruction), and Rec 15/2739 (alpha1a selective antagonist) does not improve symptom scores in BPH, our findings suggest bladder alpha1dARs may provide a potentially novel mechanism underlying these therapeutic benefits.

Animals↗

Transcriptional regulation of the human alpha1a-adrenergic receptor gene. Characterization Of the 5'-regulatory and promoter region.

We recently cloned cDNAs encoding three subtypes of human alpha1-adrenergic receptors (alpha1ARs), alpha1a, alpha1b, and alpha1d (Schwinn, D. A., Johnston, G. L., Page, S. O., Mosley, M. J., Wilson, K. H., Worman, N. P., Campbell, S., Fidock, M. D., Furness, L. M., Parry-Smith, D. J., Peter, B., and Bailey, D. S. (1995) J. Pharmacol. Exp. Ther. 272, 134-142) and demonstrated predominance of alpha1aARs in many human tissues (Price, D. T., Lefkowitz, R. J., Caron, M. G., Berkowitz, D., and Schwinn, D. A. (1994) Mol. Pharmacol. 45, 171-175). Several lines of evidence indicate that alpha1aARs are important in clinical diseases such as myocardial hypertrophy and benign prostatic hyperplasia. Therefore, we initiated studies to understand mechanisms underlying regulation of alpha1aAR gene transcription. A genomic clone containing 6.2 kb of 5'-untranslated region of the human alpha1aAR gene was recently isolated. Ribonuclease protection and primer extension assays indicate that alpha1aAR gene transcription occurs at multiple initiation sites with the major site located 696 base pairs upstream of the ATG, where a classic initiator sequence is located. Transfection of luciferase reporter constructs containing varying amounts of 5'-untranslated region into human SK-N-MC neuroblastoma cells indicate that a region extending 125 base pairs upstream from the main transcription initiation site contains full alpha1aAR promoter activity. Furthermore, distinct activator and suppressor elements lie 2-3 and 3-5 kilobase pairs upstream, respectively. Although the alpha1aAR promoter contains neither TATA or CAAT elements, gel shift mobility assays targeting three GC boxes immediately upstream of the main transcription initiation site confirm binding of Sp1. Activity of the alpha1aAR promoter is cell-specific, demonstrating highest activity in cells endogenously expressing alpha1aARs. The human alpha1aAR gene also contains several cis regulatory elements, including several insulin and cAMP response elements. Consistent with these observations, we provide the first evidence that treatment of SK-N-MC cells with insulin and cAMP elevating agents leads to an increase in alpha1aAR expression. In conclusion, these data represent the first characterization of the alpha1aAR gene; our findings should facilitate further studies designed to understand mechanisms regulating alpha1AR subtype-specific expression in healthy and diseased human tissue.

Cloning, Molecular↗

Role of noradrenergic hyperactivity in neonatal opiate abstinence.

Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the alpha 2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.

Adrenergic alpha-Agonists↗

Application of linear optimization techniques to MRI phase contrast blood flow measurements.

The goal of this study was to use linear optimization techniques as a systematic method of cine phase contrast pulse sequence design and to apply this technique to the measurement of blood flow in vivo. The optimized waveforms were validated in a constant flow phantom with average velocities ranging from 5 to 50 cm/s. The same optimized sequence was also run in a segmented k-space variation with five phase encoding lines per segment. The magnetic resonance (MR) derived velocity measurements were accurate over the entire range of velocities tested (p < .05) in both cases. The same optimized pulse sequence was applied to the measurement of flow in main pulmonary artery of five normal volunteers and compared with stroke volumes and cardiac outputs calculated from right ventricular volume measurements. These measurements showed a mean difference between the MR phase contrast calculated stroke volume and the volumetric stroke volume measurement of 9.8 +/- 11.6%. The mean difference between the calculated phase contrast cardiac output and the volumetric cardiac output was 4.4 +/- 10%. These results imply that optimization techniques are an efficient method for designing cine phase contrast pulse sequences.

Adult↗

Use of magnetic resonance imaging and P-31 magnetic resonance spectroscopy to detect and quantify muscle dysfunction in the amyopathic and myopathic variants of dermatomyositis.

OBJECTIVE: To investigate the use of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in characterizing the metabolic and functional status of muscles in patients with amyopathic dermatomyositis (DM) and to compare the findings with those in patients with classic myopathic DM. METHODS: Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11 normal individuals were studied. MRI images of thigh muscles were obtained, and T1 and T2 relaxation times were calculated. Biochemical status was quantitated with P-31 MRS, by determining concentrations of phosphate metabolites during rest and exercise. RESULTS: Patients with amyopathic DM showed no muscle inflammation, and MRS data obtained during rest were normal. During exercise at 25% and 50% maximum voluntary contractile force, the MRS data revealed significant differences between amyopathic DM patients and control subjects indicating inefficient metabolism. In contrast, muscles of patients with myopathic DM showed inflammation and metabolic abnormalities even during rest. CONCLUSION: Metabolic deficiencies in patients with amyopathic DM were unmasked by exercise, suggesting that the 2 DM syndromes may share muscle abnormalities. MRI/MRS may be useful in diagnosis and optimization of treatment.

Adult↗

In vivo localized proton NMR spectroscopy of thiamine-deficient rat brain.

Thiamine deficiency (TD) in rats produces lesions similar to those found in humans suffering from Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 29) were deprived of thiamine via a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist pyrithiamine hydrobromide. Spectra were obtained by using the STEAM sequence. No significant change occurred in the ratio of Cr/NAA, while the ratio of Cho/NAA declined significantly (60 +/- 11%) on Day 14. Eleven rats received intraperitoneal injections of thiamine hydrochloride at the end of 12 days, and dose-dependent recovery in Cho/NAA was observed.

Alcohol Amnestic Disorder↗

Design and evaluation of a flow phantom.

RATIONALE AND OBJECTIVES: We constructed a near-anatomically correct large-vessel phantom to perform repeatable flow dynamics research examinations by angiography, magnetic resonance (MR) angiography, and computed tomography (CT) angiography. METHODS: An internal carotid artery was constructed within a head phantom. The internal carotid artery branches into a middle and an anterior cerebral artery; the former trifurcates and ends in the superior sagittal sinus, and the latter ends in the inferior sagittal sinus. A transverse and sigmoid sinus drains the model. All four vessels connecting the arterial and venous vessels have variable flow-constricting ligatures placed around them. These ligatures are accessible on the skull surface. The skull cavity is filled with a silicone polymer that is isodense to brain on CT scans and isointense on most MR images. RESULTS: The flow in the phantom's vessels may be varied in a repeatable manner. Multiple scan sequences may be performed without the image degradation caused by patient motion. The homogeneity of the filler polymer allows visualization of flow-related artifacts that may be hidden by complex human anatomy. CONCLUSION: Preliminary images of each modality show promise for use of the phantom in imaging research on large-vessel flow dynamics.

Cerebral Angiography↗

The AAPM/RSNA physics tutorial for residents. Contrast mechanisms in gradient-echo imaging and an introduction to fast imaging.

The strengths of spin-echo sequences in clinical magnetic resonance imaging are its relative insensitivity to magnetic field inhomogeneities and its versatility; however, they require relatively long imaging times. Use of gradient-echo sequences largely circumvents the problem. A gradient echo is created by means of a gradient reversal following a single radio-frequency (RF) pulse, typically with a flip angle that is less than 90 degrees, compared with a spin-echo sequence, which requires at least two RF pulses, typically a 90 degree excitation pulse followed by a 180 degree refocusing pulse. The shortened repetition times (TRs) in gradient-echo sequences together with small flip angles enable maintaining adequate image signal-to-noise ratios while still achieving a short imaging time. Numerous gradient-echo sequences have been developed, with the most common being (a) fast low angle shot (FLASH), which uses small flip angles and short TRs; (b) gradient-recalled acquisition in the steady state and fast imaging with steady-state precession (GRASS/FISP); (c) magnetization-prepared rapid gradient echo (MP-RAGE); and (d) echo planar. The shorter imaging times made possible through gradient-echo sequences are used clinically to minimize patient motion artifacts and to allow isotropic three-dimensional imaging with acceptable imaging times.

Contrast Media↗

Quality of clinical MR images and the use of contrast agents.

Attempts to optimize the quality of magnetic resonance images must balance the competing needs for high spatial resolution, high signal-to-noise ratio, a large number of sections, and a reasonable imaging time. These factors, which determine the ultimate image quality, are affected by a number of variables, including the field of view, the matrix and pixel size, choice of repetition time and echo time, section thickness, and the number of signals averaged. The manner in which these variables interrelate and their effect on the ultimate image quality are important in order to craft the most appropriate examination for each individual patient. A second major effect on soft-tissue contrast is the use of paramagnetic agents. The spectrum of utility of these agents within the central nervous system and the body is increasing. A large number of new agents are also being investigated, primarily for use outside the central nervous system.

Contrast Media↗