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Biomedical subjects

R Hurd

Publications and source records attributed to R Hurd.

18 recordsLinked to original sources

Very selective suppression pulses for clinical MRSI studies of brain and prostate cancer.

Focal three-dimensional magnetic resonance spectroscopic imaging (3D MRSI) methods based on conventional point resolved spectroscopy (PRESS) localization are compromised by the geometric restrictions in volume prescription and by chemical shift registration errors. Outer volume saturation (OVS) pulses have been applied to address the geometric limits, but conventional OVS pulses do little to overcome chemical shift registration error, are not particularly selective, and often leave substantial signals that can degrade the spectra of interest. In this paper, an optimized sequence of quadratic phase pulses is introduced to provide very selective spatial suppression with improved B1 and T1 insensitivity. This method was then validated in volunteer studies and in clinical 3D MRSI exams of brain tumors and prostate cancer.

Brain Neoplasms↗

Monosaccharide-enriched diets cause hyperleptinemia without hypophagia.

To determine the effect of monosaccharide-enriched diets on plasma leptin and food consumption, body weight, food intake, and serum glucose, insulin, and leptin concentrations were measured in rats maintained on a 10-d course of 60% glucose or 60% fructose diet. The serum leptin concentration in rats fed a high-glucose diet (7.60 +/- 0.6 ng/mL) or a high-fructose diet (5.12 +/- 0.8 ng/mL) was significantly increased compared with that in control rats (2.45 +/- 0.10 ng/mL; P < 0.001). To ascertain that the observed effect was related to hyperinsulinemia, a group of rats were infused with exogenous insulin or rendered insulin resistent with a high-fat diet. When hyperinsulinemia was induced with exogenous infusion, the serum leptin was increased (5.56 +/- 0.23 ng/mL; P < 0.001). High-fat feeding was associated with increased serum leptin (12.1 +/- 1.4 ng/mL) and insulin levels. The increased serum leptin concentration was not associated with decreased food intake. We conclude that monosaccharide-enriched diets, probably through hyperinsulinemia or relative or absolute insulin resistance, cause hyperleptinemia, which does not appear to change feeding behavior.

Animals↗

Age-related changes in plasma leptin binding activity in rats: A comparison of a simple acid-ethanol precipitation technique with column chromatography.

A novel assay for measuring the free leptin fraction was developed and validated against a chromatographic technique. The assay used acid-ethanol extraction (AEE) for separation of bound/free leptin moieties. The interassay coefficient of variation was 3.9%. The specificity for leptin binding was confirmed by incubation with 1 microg of unlabeled rat leptin that effectively competed with radiolabeled leptin whereas human growth hormone and interleukin-6 were ineffective in competing with radiolabeled leptin binding. Scatchard analysis of competitive binding experiments with rat plasma demonstrated a linear relationship with a binding affinity of 0.3-0.6 x 109 M-1. This novel assay was used to determine if age-related insensitivity to leptin action is secondary to altered serum leptin binding. Rats at various age groups were studied for changes in body adiposity and serum total and free leptin concentrations. Serum free leptin concentrations (ng/ml mean +/- SEM) were significantly increased in 24-month-old rats (5.56 +/- 0. 21) compared with 18-month-old rats (4.76 +/- 0.17) (P < 0.01) despite similar body weight and adiposity of the two age groups. The increase in plasma free leptin concentrations in 12-month-old rats (3.86 +/- 0.28) and 6-month-old rats (2.05 +/- 0.06) relative to 3-month-old rats (1.37 +/- 0.06) (P < 0.001) was out of proportion to the increase in body adiposity in aging rats. It is concluded that aging in rats is associated with relative insensitivity to leptin. This change cannot be attributed to increased plasma binding or to a reduction in the leptin free fraction.

Adipose Tissue↗

Spatial distribution of deoxymyoglobin in human muscle: an index of local tissue oxygenation.

The proximal histidyl NdeltaH signal of myoglobin is detectable in 1H NMR spectra of myocardial and skeletal muscle, and its intensity reflects the intracellular oxygenation. At 1.5 Tesla (T), the typical field strength of clinical magnetic resonance imaging (MRI) magnets, the paramagnetic relaxation contribution decreases sufficiently to permit the implementation of chemical shift imaging technique to map the spatial distribution of the deoxy Mb NdeltaH signal from human gastrocnemius muscle. One and two-dimensional chemical shift imaging experiments reveal clearly the localized deoxy Mb signal in muscle and consequently the spatial distribution of the cellular oxygenation. The results indicate the feasibility to assess the pO2 in tissue regions and to directly study the regulation of oxidative metabolism in human tissue.

Humans↗

Comparative analysis of NMR and NIRS measurements of intracellular PO2 in human skeletal muscle.

1H NMR has detected both the deoxygenated proximal histidyl NdeltaH signals of myoglobin (deoxyMb) and deoxygenated Hb (deoxyHb) from human gastrocnemius muscle. Exercising the muscle or pressure cuffing the leg to reduce blood flow elicits the appearance of the deoxyMb signal, which increases in intensity as cellular PO2 decreases. The deoxyMb signal is detected with a 45-s time resolution and reaches a steady-state level within 5 min of pressure cuffing. Its desaturation kinetics match those observed in the near-infrared spectroscopy (NIRS) experiments, implying that the NIRS signals are actually monitoring Mb desaturation. That interpretation is consistent with the signal intensity and desaturation of the deoxyHb proximal histidyl NdeltaH signal from the beta-subunit at 73 parts per million. The experimental results establish the feasibility and methodology to observe the deoxyMb and Hb signals in skeletal muscle, help clarify the origin of the NIRS signal, and set a stage for continuing study of O2 regulation in skeletal muscle.

Adult↗

Myoglobin desaturation with exercise intensity in human gastrocnemius muscle.

The present study evaluated whether intracellular partial pressure of O(2) (PO(2)) modulates the muscle O(2) uptake (VO(2)) as exercise intensity increased. Indirect calorimetry followed VO(2), whereas nuclear magnetic resonance (NMR) monitored the high-energy phosphate levels, intracellular pH, and intracellular PO(2) in the gastrocnemius muscle of four untrained subjects at rest, during plantar flexion exercise with a constant load at a repetition rate of 0.75, 0.92, and 1.17 Hz, and during postexercise recovery. VO(2) increased linearly with exercise intensity and peaked at 1.17 Hz (15. 1 +/- 0.37 watts), when the subjects could maintain the exercise for only 3 min. VO(2) reached a peak value of 13.0 +/- 1.59 ml O(2). min(-1). 100 ml leg volume(-1). The (31)P spectra indicated that phosphocreatine decreased to 32% of its resting value, whereas intracellular pH decreased linearly with power output, reaching 6.86. Muscle ATP concentration, however, remained constant throughout the exercise protocol. The (1)H NMR deoxymyoglobin signal, reflecting the cellular PO(2), decreased in proportion to increments in power output and VO(2). At the highest exercise intensity and peak VO(2), myoglobin was approximately 50% desaturated. These findings, taken together, suggest that the O(2) gradient from hemoglobin to the mitochondria can modulate the O(2) flux to meet the increased VO(2) in exercising muscle, but declining cellular PO(2) during enhanced mitochondrial respiration suggests that O(2) availability is not limiting VO(2) during exercise.

Adolescent↗

Decoupling: theory and practice. II. State of the art: in vivo applications of decoupling.

Current methods for broadband heteronuclear decoupling are reviewed from a historical perspective. The principal concern is that decoupling should be effective over a wide range of chemical shifts without undue radiofrequency heating of the sample, particularly when human patients are involved. Continuous-wave methods are the least efficient in this respect, followed by noise decoupling. Composite pulse schemes offer a more effective use of radiofrequency power, while adiabatic passage methods are the most efficient of all. Bi-level decoupling employs a low level of radiofrequency irradiation during the relaxation delay to maintain the nuclear Overhauser effect, with a higher level during signal acquisition in order to decouple over a wide frequency band. All decoupling sequences introduce cycling sidebands into the observed spectrum, and schemes are described to minimize the intensity of these artifacts. In part II, practical applications of decoupling methods are examined in the context of in vivo spectroscopy, where the improvements in sensitivity and resolution through broadband decoupling can be critical for solving clinical problems. Attention is focused on the regulatory limits on power deposition in these experiments. A tabulation of the existing work on decoupling in biological tissue is presented, mainly involving 31P and 13C spectroscopy in vivo or in vitro.

Humans↗

Abnormalities of antioxidant metabolism in a case of Friedreich's disease.

We report a patient with Friedreich's disease (FD) who exhibited abnormalities of antioxidant metabolism, including decreased levels of glutathione peroxidase, glutathione reductase, and selenium, and an increased lipid peroxide index. These abnormalities became normal after treatment with N-acetylcysteine, selenium, and low-dose vitamin E therapy. Treatment was associated with a decreased rate of clinical decline. FD is a neurodegenerative disorder that may be related to disturbed antioxidant metabolism; the disorder may be treatable with antioxidant compounds.

Acetylcysteine↗

Short TE phosphorus spectroscopy using a spin-echo pulse.

In vivo phosphorus spectroscopy requires very short acquisition delays in order to capture the signal from components with short transverse relaxation times (T2). The echo time typical of standard slice selective spin-echo pulses are too long for this application, so hard pulse, free induction decay (FID) acquisitions have frequently been used instead. With FID, however, there is an interval between the time of coherence and data acquisition (acquisition delay), with resulting baseline distortions. In this paper we describe the design of a new short TE, slice-selective, composite spin-echo pulse with echo times as short as 2.5 ms. With a long TR, fully relaxed, multislice spectra can be collected. This technique will be useful for assessing in vivo, changes in brain phospholipid activity associated with psychiatric and neurological diseases.

Brain↗

Evaluation of the clinical performance of automated proton magnetic resonance spectroscopy in children.

RATIONALE AND OBJECTIVES: Because expeditious neuroimaging is imperative in pediatric patients, we evaluated automated procedures for proton magnetic resonance spectroscopy (1H MRS) of the brain of children. METHODS: 1H MRS was performed on a 1.5-T GE Signa. The protocol included stimulated echo-acquisition mode and spin-echo point resolved spectroscopy. The automated routine included adjustment of first-order gradient shims (x, y, z1) to optimize magnetic field homogeneity, transmit power, center frequency, receiver gain, and water suppression. All spectra were processed with the use of spectroscopy analysis software from General Electric on a Sun workstation. RESULTS: The use of the automated procedures reduced the length of our 1H MRS protocol by 50%. Magnetic field homogeneity was within our accepted standards (7 +/- 2 Hz). Water suppression was within range of our accepted factors (1000-10,000). However, on certain occasions, baseline distortions affected resonances in the 3.22-4.04 ppm range. CONCLUSIONS: Shortening of the time required for clinical 1H MRS will increase its application in evaluating children.

Brain↗

19F magnetic resonance imaging of the reticuloendothelial system.

In this study sequential 1H and 19F magnetic resonance imaging methods were used to map the distribution of fluorinated compounds in vivo. An intravenously administered emulsion of perfluorooctylbromide (PFOB), an agent known to localize in the reticuloendothelial system, was detected in the liver and spleen of all studied hamsters and mice using 19F MRI. Lungs and salivary glands were also affected in some animals. Using a G. E. NMR CSI 2-T spectroscopy/imaging system, projection 19F images were obtained in 4 to 8 min. Subsequent mouse studies using a thick-slice driven equilibrium pulse sequence produced 19F images with an improved signal-to-noise ratio in a shorter acquisition time. With PFOB, 19F MRI has the capability of detecting macrophages in the reticulo-endothelial system and in other sites where macrophages congregate. This is the first report where the reticuloendothelial system was specifically imaged in live animals and where driven equilibrium imaging techniques have been applied to 19F MRI.

Animals↗

Selective peritoneal lavage in the management of comatose blunt trauma patients.

Comatose blunt trauma patients undergo diagnostic peritoneal lavage to aid in the management of severe injuries. In deference to routine performance of lavage, patients felt to be a risk for abdominal injury were prospectively studied by using selective criteria for lavage. One hundred consecutive comatose blunt trauma patients were studied; five underwent urgent celiotomy for refractory hypotension. Five criteria for lavage were: history of postinjury hypotension, abdominal physical findings suggestive of underlying abdominal injuries, evidence of fracture of the bones of the trunk and/or femur, blunt trauma of unknown etiology, and operative general anesthesia required for nonabdominal injuries. Fifty-five patients satisfied at least one of the above criteria and underwent peritoneal lavage. Forty patients not satisfying the criteria were observed without peritoneal lavage, as it was felt they had a decreased probability of serious abdominal injury. One of these patients had a minor liver laceration found at the time of autopsy following his death from severe head injury. None of the other patients had evidence of intra-abdominal injury by autopsy or subsequent clinical course. Utilizing the selective criteria, none of the 100 consecutive blunt trauma patients had major delay in abdominal diagnosis or missed significant abdominal pathology defined by operation, clinical course, or autopsy. Routine peritoneal lavage in all comatose blunt trauma patients may subject the patient to unnecessary risk, waste valuable time, increase the cost of care, and alter subsequent diagnostic procedures. Based on this small study, it appears that comatose blunt trauma victims not fulfilling the criteria may be effectively evaluated without the use of peritoneal lavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗

Major pelvic fractures.

Pelvic fractures associated with blunt trauma contributed significantly to morbidity and mortality in 593 patients with high-velocity deceleration injuries. Those with open, hemorrhagic pelvic fractures required massive blood volume replacement and intensive care for long periods of time and had a 60% mortality. Patients with hemorrhagic pelvic fractures also had a notable blood replacement requirement (mean, 29 units) and a 50% mortality. Patients with open pelvic fractures without significant hemorrhage had a 25% mortality and were at an increased risk of pelvic sepsis. The overall mortality associated with pelvic fractures following high-velocity deceleration accidents was 16.6%. The identifiable causes of death in patients with pelvic fractures were associated injuries, particularly closed head injury, hemorrhage from pelvic vessels, and sepsis. An improved survival rate requires better, more prompt use of available treatment, as well as development of new and better methods of caring for severely injured patients with blunt trauma.

Adolescent↗

Folic acid and vitamin D status of young children receiving minimal anticonvulsant drug therapy.

The effects of long term, low dosage anticonvulsant drug therapy on the vitamin D and folacin status of young children was studied. Biochemical and dietary parameters including serum calcium, phosphorous and alkaline phosphatase; serum and red blood cell folacin; serum drug concentrations; hematocrits; and dietary intakes of vitamin D and folacin were measured in seven subjects. All subjects were taking low dosages of medication. Four subjects were considered at risk for developing a folacin deficiency based on red blood cell folacin concentrations. Two of these subjects had inadequate dietary intakes of folacin. Serum calcium and alkaline phosphatase levels were within normal ranges for all subjects; two subjects had subnormal levels of serum phosphorous. Dietary intake of vitamin D was below fifty percent of the Recommended Dietary Allowance for four subjects. The data of the present study suggest that young children undergoing chronic anticonvulsant drug therapy of minimal dosage are susceptible to developing folacin deficiency especially if dietary intake of folacin is inadequate. These children do not appear to be at risk for developing vitamin D deficiency probably due to the low dosage of medication coupled with adequate sunlight exposure.

Alkaline Phosphatase↗