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Biomedical subjects

B L Nichols

Publications and source records attributed to B L Nichols.

At least 109 records · Page 6Linked to original sources

Sequential changes in body composition during infection: electron probe study IV.

Alterations occur in human muscle electrolyte and water composition in response to infection. There appear to be at least two basic mechanisms; the first is an exchange of sodium for potassium without alteration in water content of muscle. The second is an increase in cellular Na and water without a loss of K on a dry weight basis. In a series of studies in monkeys, Salmonella typhimurium sepsis was induced as an experimental model. Both patterns of muscle response to infection were detected. Electron probe microanalysis revealed that the loss of K concentration was due to an accumulation of intracellular saline which dilute the K content. The mechanism of this is unclear; however, a concomitant increase in undertermined osmoles in the serum suggests that there may be an increase in organic osmoles within the cell which leads to the dilution of intracellular K concentration.

Animals↗

Luminal dilatation and morphologic changes secondary to enterotoxins.

Structural changes in ligated rat small intestinal loops exposed to purified cholera enterotoxin are described. Distention secondary to increased luminal fluid was found to cause the artifactual histologic damage. This finding questions the validity of interpreting mucosal changes in closed intestinal-loop models in the presence of severe distention. An alternative open-loop model is described that eliminates distention as a cause of histologic changes.

Animals↗

Treatment of skin irritation around enterostomies with cholestyramine ointment.

Eight patients with inflammation of the skin about the cutaneous stoma responded to local application of a 20% cholestyramine ointment in a short period of time. Two children treated with the hydrophilic base (Aquaphor) alone did not respond to treatment. The ileal bile acid patterns of two children with ileostomies were found to be different from that of the control group. Ileostomy patients had a higher concentration for total bile acids and a higher percentage of free bile acids.

Bile Acids and Salts↗

Modular Formula: an approach to management of infants with specific or complex food intolerances.

Modular Formula is a dietary preparation for use in treating infants with complex malabsorptive disorders and for weaning infants from total parenteral nutrition. With this formula the physician can alter the quality of the various nutrients normally fed to infants as well as concentrations of those nutrients. Infants who cannot tolerate existing proprietary formulas will often thrive with the judicious use of this flexible formula. Modular Formula provides the clinician with a useful aid in the diagnosis and treatment of chronic diarrhea of infancy.

Diarrhea, Infantile↗

Comparison of patterns of fecal bile acid and neutral sterol between children and adults.

The patterns of bile acids and neutral sterols in the feces of five infants under 1 1/2 years of age, five children 4 years of age, and nine adult subjects without histroy of gastrointestinal diseases were studied by gas-liquid chromatography. Progressive changes in both bile acid and neutral sterol profiles were observed with maturation in infants and children. The patterns in the 4 year olds appraoched those observed in adults. In the infants under 1 1/2 years, cholic and chenodeoxycholic acids constituted 20.7 +/- 4.8% and 7.5 +/- 2.3% of the total bile acid in the stool, respectively. Deoxycholic and lithocholic acids made up only 4.4 +/- 1.7% and 2.9 +/- 1.0%, respectively. In the 4 year olds, the corresponding primary bile acids decreased to 3.9 +/- 1.9% and 5.6 +/- 4.3%, whereas secondary bile acids increased to 21.3 +/- 5.4% and 33.2 +/- 2.2%. Normal adults on regular mixed diets had only small amounts of primary bile acids (2.4 +/- 0.5% and 3.4 +/- 0.6% for cholic and chenodeoxycholic acids). The secondary bile acids in their feces were 34.3 +/- 2.2% and 38.9 +/- 2.0%, respectively. In the neutral sterol fraction, unmodified cholesterol decreased with age: 94.7 +/- 3.7%, 27.0 +/- 1.5% and 25.0 +/- 4.8% of the total neutral sterols in the feces for infants, children, and adults, respectively. On the other hand, coprostanol, the principal metabolite of cholesterol in humans, increased with age: 3.8 +/- 3.4%, 62.6 +/- 3.5% and 65.8 +/- 4.7% for the respective groups. Total bile acid excretion expressed as mg/day, also increased with age: 34 +/- 17, 47 +/- 17 and 293 +/- 69 (for five adult subjects only) for the respective groups. These differences disappeared, however, when the data were expressed as mg/kg of body weight per day: 3.8 +/- 2.0, 3.0 +/- 1.1, and 4.1 +/- 1.0 for the respective groups. Daily excretion of cholesterol metabolites, when expressed as mg/day increased with age: 139 +/- 38, 278 +/- 54 and 719 +/- 211 (for five adult subjects only) for the respective groups. The corresponding values after correction by body weight were 15.4 +/- 4.5, 17.9 +/- 3.0 and 10.3 +/-3.0 mg/kg per day for the respective groups. The production of coprostanol was correlated with 7 alpha-dehydroxylation of cholic acid and chenodeoxycholic acid.

Adult↗

Fecal steroids in diarrhea. I. Acute shigellosis.

Fecal bile acid and neutral sterol patterns of five healthy adult male volunteers, who were challenged by a virulent Shigella flexneri 2a (M42-43) strain and developed dysentery were studied. It was observed that cholic acid was increased from 1.9 +/- 0.4% of total bile acid in the feces before infection to 14.5 +/- 2.1% during diarrhea (P less than 0.001). Chenodeoxycholic acid also was increased from 3.2 +/- 0.7 to 8.7 +/- 3.2% in diarrhea but the difference was not significant statistically. Deoxycholic and lithocholic acids constituted 34.1 +/- 4.1 and 40.5 +/- 2.8%, respectively, of total bile acid in the normal controls as compared to 13.9 +/- 2.5 and 24.8 +/- 2.5% for the same subjects during diarrhea (P less than 0.005). Total excretion of bile acids, expressed as mg/kg of body weight per day, were higher in diarrhea (5.4 +/- 1.0) than that in controls (4,2 +/- 1.0) but the difference was not statistically significant. In the neutral sterol fraction, unmodified cholesterol was increased during diarrhea (86.2 +/- 8.7 versus 25.0 +/- 4.8% of total cholesterol metabolites in controls, P less than 0.001). Coprostanol was decreased in shigellosis (12.2 +/- 8.2 versus 65.8 +/- 4.7% in controls, P less than 0.001). Epicoprostanol, coprostanone, and unidentified cholesterol metabolites also were reduced in shigellosis. The effect of diarrhea on the plant sterols was not as consistent. However, unidentified plant sterols were reduced significantly in shigellosis stools. Total excretion of cholesterol metabolites and plant sterols, when expressed as mg/kg of body weight per day, were 6.8 +/- 1.7 and 0.6 +/- 0.2), respectively, in Shigellosis. These values were not significantly different from the corresponding values for controls (10.3 +/- 3.0 and 0.8 +/- 0.2). One subject's stool samples were studied during infection for the sequence of bile acid alteration. A progressive reduction of bacterial activity upon fecal steroids was evident following the initial diarrheal episode. The production of coprostanol was correlated with 7 alpha-dehydroxylation of cholic acid (r = 0.937, P less than 0.001) and chenodeoxycholic acid (r = 0.755, P less than 0.01).

Acute Disease↗

Effects of DOCA on circulation, renal functions, body fluids and tissue electrolytes.

Desoxycorticosterone acetate (DOCA) was administered subcutaneously to 11 normal dogs (2 mg/kg/day) for 4 days. Few changes were observed in cardiovascular and renal functions except that the glomerular filtration rate was significantly increased. Total body water and plasma volume increased with a reduction of red blood cell volume. Hematocrit, plasma osmolality and total protein concentrations were decreased. The plasma K+ levels were lowered despite unchanged plasma concentrations of Na+, Ca++, Mg++, Cl- and phosphorus. The heart showed an increase in Na+ content and a decrease in K+, Ca++, phosphorus and total lipids. The skeletal muscle showed a decrease in Ca++ and an increase in Cl- and water content. The skin revealed a reduction of K+ and an elevation of Cl-. This study showed that a DOCA-induced depletion of K+ from skeletal muscle did not occur in normally fed dogs that did not receive a large sodium load.

Animals↗

Electrolyte metabolism of muscle in the salt-losing form of congenital adrenal hyperplasia.

The study of metabolism of muscle electrolyte in children with the salt-losing form of congenital adrenal hyperplasia reveals two types of alterations. After admission and during initial therapy with salt and desoxycorticosterone, the changes are typical of those seen in experimental animals with adrenalectomy and excessive replacement therapy. Discontinuation of the sodium supplement after three months of therapy resulted in a return of muscle electrolyte values to normal. During the period of poor growth common to these patients a different pattern was observed. Sodium and water accumulated without alteration in tissue potassium. The mechanism of this alteration is not clear; however, it is consistent with the known effects of excess cortisone on muscle composition. These observations permit the conclusion that at least two fractions of sodium are present in muscle fibers, that which exchanges potassium and that which is independent of potassium metabolism.

17-Ketosteroids↗

Variation in the phenotypic expression of beta-glucuronidase deficiency.

Defiency of beta-glucuronidase was demonstrated in serum, leukocytes, and cultured skin fibroblasts of two unrelated patients. One patient died at 2 9/12 years with a phenotype consistent with severe mucopolysaccharidosis; the other is 14 years of age and well, except for hypertension and obstructive lesions of large blood vessels. Analysis of urinary mucopolysaccharides revealed impaired degradation of dermatan sulfate and, to a lesser extent, of heparan sulfate. Cultured skin fibroblasts accumulated excess glycosaminoglycans (the term glycosaminoglycans is synonymous with acid mucopolysaccharides) as indicated by 35-SO-4 uptake.

Adolescent↗

The effects of cholera enterotoxin on intestinal tissue water as measured by nuclear magnetic resonance (NMR) spectroscopy.

Cholera enterotoxin has been postulated to change the configuration of the intracellular protein-water system, altering the permeability of the cell to water. Using nuclear magnetic resonance (NMR) spectroscopy, this protein-water relationship can be examined. Small intestinal loops in the rat were injected with 0.5 ml of either Schwarz/Mann cholera enterotoxin (40 mug/cc saline solution) or normal saline. Full thickness segments of intestine from each loop were taken and percentage water (using a gravimetric procedure which includes a correction for fat) and NMR relaxation times were determined. The mean value +/- S.D. for tissue water was 79.49 +/- 2.65% in the controls and 84.52 +/- 2.01% in the cholera specimens (p less than .001). T1 (spin-lattice) relaxation times were 521.22 +/- 69.5 msec in the controls and 667.96 +/- 119.25 msec in cholera tissue (p less than .001). T2 (spin-spin) relaxation times were 62.34 +/- 9.59 msec in controls and 80.35 +/- 21.46 msec in cholera tissue (p less than .02). These findings are consistent with the theory that cholera enterotoxin acts to alter intracellular protein-water relationship.

Animals↗

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.

Animals↗