Carlton F. Hazlewood

Nuclear Magnetic Resonance Transverse Relaxation Times of Water Protons in Skeletal Muscle

The observation of the spin-echo decay in a long time domain has revealed that there exist at least three different fractions of non- (or slowly) exchanging water in the rat gastrocnemius muscle. These fractions of water are characterized with different nuclear magnetic resonance (NMR) relaxation times and are identified with the different parts of tissue water. The water associated with the macromolecules was found to be approximately 8% of the total tissue water and not to exchange rapidly with the rest of the intracellular water. The transverse relaxation time (T(2)) of the myoplasm is 45 ms which is roughly a 40-fold reduction from that of a dilute electrolyte solution. This fraction of water accounts for 82% of the tissue water. The reduced relaxation time is shown neither to be caused by fast exchange between the hydration and myoplasmic water nor by the diffusion of water across the local magnetic field gradients which arise from the heterogeneity in the sample. About 10% of the tissue water was resolved to be associated with the extracellular space, the relaxation time of which is approximately four times that of the myoplasm. Mathematical treatments of the proposed mechanisms which may be responsible for the reduction of tissue water relaxation times are given in this paper. The results of our study are consistent with the notion that the structure and/or motions of all or part of the cellular water are affected by the macromolecular interface and this causes a change in the NMR relaxation rates.

Response of pain to static magnetic fields in postpolio patients: A double-blind pilot study

OBJECTIVE To determine if the chronic pain frequently presented by postpolio patients can be relieved by application of magnetic fields applied directly over an identified pain trigger point. DESIGN Double-blind randomized clinical trial. SETTING The postpolio clinic of a large rehabilitation hospital. PATIENTS Fifty patients with diagnosed postpolio syndrome who reported muscular or arthritic-like pain. INTERVENTION Application of active or placebo 300 to 500 Gauss magnetic devices to the affected area for 45 minutes. MAIN OUTCOME MEASURE Score on the McGill Pain Questionnaire. RESULTS Patients who received the active device experienced an average pain score decrease of 4.4 +/- 3.1 (p < .0001) on a 10-point scale. Those with the placebo devices experienced a decrease of 1.1 +/- 1.6 points (p < .005). The proportion of patients in the active-device group who reported a pain score decrease greater than the average placebo effect was 76%, compared with 19% in the placebo-device group (p < .0001). CONCLUSIONS The application of a device delivering static magnetic fields of 300 to 500 Gauss over a pain trigger point results in significant and prompt relief of pain in postpolio subjects.

Cellular responses to extreme water loss: The water-replacement hypothesis☆

The previously advanced hypothesis that desiccation resistance involves the replacement of water adjacent to intracellular surfaces with polyhydroxy compounds has been supported by experiments on cysts of the brine shrimp, Artemia, and in a model system of albumin--glycerol--water, using nuclear magnetic resonance spectroscopy, microwave dielectrics, and density measurements. We have also considered other problems that cells face when large fractions of their total water content are removed. Observations by other investigators have indicated that a variety of mammalian cells can lose roughly 50% of their water and survive; for a given cell type death occurs if its volume is reduced below a certain minimum level. Membrane damage has previously been suggested to be a major cause of dehydration damage. We have proposed some additional plausible mechanisms that might also be involved.

Distinction between the Preneoplastic and Neoplastic State of Murine Mammary Glands

We have, using nuclear magnetic resonance spectroscopy, measured the relaxation times and diffusion coefficient of water protons in primary mammary adenocarcinomas of mice. In our biological model, three morphological stages were defined: (a) mammary gland tissue from pregnant mice, (b) preneoplastic nodules, and (c) neoplastic tissue. It was found that neoplastic tissues could be distinguished from normal and prenoeplastic tissue. Spin-spin and spin-lattice relaxation times and the diffusion coefficient of water protons are increased in the neoplastic tissue relative to mammary gland tissue from pregnant mice and preneoplastic nodule tissue.

Diffusive properties of water in Artemia cysts as determined from quasi-elastic neutron scattering spectra

Results have been obtained on the quasi-elastic spectra of neutrons scattered from pure water, a 20% agarose gel (hydration four grams H2O per gram of dry solid) and cysts of the brine shrimp Artemia for hydrations between 0.10 and 1.2 grams H2O per gram of dry solids. The spectra were interpreted using a two-component model that included contributions from the covalently bonded protons and the hydration water, and a mobile water fraction. The mobile fraction was described by a jump-diffusion correlation function for the translation motion and a simple diffusive orientational correlation function. The results for the line widths gamma (Q2) for pure water were in good agreement with previous measurements. The agarose results were consistent with NMR measurements that show a slightly reduced translational diffusion for the mobile water fraction. The Artemia results show that the translational diffusion coefficient of the mobile water fraction was greatly reduced from that of pure water. The line width was determined mainly by the rotational motion, which was also substantially reduced from the pure water value as determined from dielectric relaxation studies. The translational and rotational diffusion parameters were consistent with the NMR measurements of diffusion and relaxation. Values for the hydration fraction and the mean square thermal displacement [u2] as determined from the Q-dependence of the line areas were also obtained.

The spin-lattice relaxation times of water associated with early post mortem changes in skeletal muscle.

We studied the spin-echo signal of muscle water in a large time domain and found that the motion of the nuclear magnetic moment of tissue water cannot be characterized by a single spin-lattice relaxation time (T1). The relaxation time T1B, which is the T1 characterized by those protons with a slower relaxation rate, is influenced by the early post mortem changes in skeletal muscle. T1B increased with time after the tissue was taken from the animal and reached a maximum at 3 h. However, the weighted average of T1 of all water protons (T1A) did not change throughout the time course of the experiments.

Distribution of Potassium, Sodium, and Chloride in Canine Purkinje and Ventricular Tissues: Relation to Cellular Potential

Cellular resting and action potentials and total tissue concentrations of K+, Na+, and Cl− were measured in canine myocardial and Purkinje tissues. The results with myocardium were consistent with those of others: the total tissue concentration of K+ was greater than that of Na+ of Cl− In Purkinje tissue, the total tissue concentration of K+ was relatively low, while that of Na+ and of Cl− was high. Extracellular space was calculated on the basis of four different assumptions about the intracellular concentration of one of the ions: (1) the intracellular concentrations of Cl− is zero; (2) the electrochemical equilibrium potential of Cl− equals the cellular resting potential; (3) the electrochemical equilibrium potential of K+ equals the cellular maximum diastolic potential; (4) the electrochemical equilibrium potential of Na+ equals the reversal of the cellular action potential. In the myocardium, the lowest estimate of extracellular space was 14±2%, and the highest was 18±2%. In the Purkinje tissue, the minimum extracellular space: (1) permitting adequate intracellular K+ to account for the maximum diastolic potential was 45±3%; (2) consistent with passive distribution of Cl− was 61±4%; (3) yielding low enough intracellular concentration of Na+ to account for the reversal of the action potential was 63±10%. These results suggest that in cardiac Purkinje tissue: (1) the extracellular space is unusually large with respect to that of myocardium and skeletal muscle; (2) intracellular activities of ions do not necessarily equal concentrations; or (3) intracellular space is not necessarily a single compartment.

Effect of electric field on physical states of cell-associated water in germinating morning glory seeds observed by 1H-NMR

Morning glory seeds in dry conditions (0.099 g H2O/dry wt.) were exposed to electric fields and germinated. The physical state of water in the germinating seeds of both control and exposed groups were examined using 1H-NMR spectroscopy and NMR microscopy. Three water fractions were observed which were characterized by different relaxation times (T1) and chemical shifts. The average region containing long T1 fractions was approximately 50 micrometer in diameter and consisted of half-permeable barriers. The maximum intracellular water transport rate was 2.3x10-5 cm2/s. The treatment with electric field (500 kV/m for 60 min) increased the fraction with the shortest T1 and decreased that with the longest T1. Because the total water content in the treated seeds (3.4 g H2O/dry wt.) was similar to that in the untreated seeds (3.9 g H2O/dry wt.), the treated seeds held more water in a condition in restricted motion than the untreated seeds. It is thought that the membrane systems were affected by the electric polarization which led to an unusual accumulation of water and the hydration of stored macromolecules during the imbibition process. This set of events led to excessive swelling of stored macromolecules, resulting in the disruption of membrane systems and irregular organization of tissue structures.

The “Systemic Effect” of Elevated Tissue and Serum Relaxation Times for Water in Animals and Humans with Cancers

In this decade, following the Damadian discovery (Science 1971) that the nuclear resonance signal would non-invasively detect disease, nuclear magnetic resonance (NMR) spectroscopy has shown potential as a tool in medical diagnosis. One area in which NMR has been utilized successfully is in the exploration of the physical properties of water in disease states, especially cancer. This chapter is specificially aimed at one phenomenon called the “systemic effect”, whereby the physical properties of water and the concentration of water are changed in distant organs and sera of animals bearing tumors. An understanding of this phenomenon and our knowledge of it can be approached from a historical perspective coupled with a presentation of the latest experimental data in this field.

Therapeutic implications of electrolyte, water, and nitrogen losses during recovery from protein-calorie malnutrition

The importance of recognizing the altered physiologic status of the child with protein-calcium malnutrition at admission and during rehabilitation is emphasized by the difference in continuing losses and in growth requirements in these periods. Features of great significance are the inability to concentrate urine at admission and during early rehabilitation, the increased urine volume resulting from higher protein intakes, and the increased dermal losses which occur with early and late catch-up growth. For the child at admission, it is suggested that whole cows milk diluted two parts with one part of a solution of 15 per cent dextrimaltose and 1.5 per cent potassium chloride will meet the water and electrolyte requirements when fed at the rate of at least 150 ml. per kilogram per day. If the child is committed to the catabolic state by gastrointestinal disturbances, an oral or intravenous infusion of a solution containing 55 mEq. of K and 25 mEq. of Na at an average rate of 120 ml. per kilogram per day will provide for the average continuing losses or maintenance requirements of water and electrolytes.