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Biomedical subjects

D R Wilson

Publications and source records attributed to D R Wilson.

At least 91 records · Page 5Linked to original sources

A community program to reward children's use of seat belts.

This paper reports on a community-wide effort to increase elementary school children's use of seat belts. Twenty-five schools serving over 9,000 children participated in a program of rewards (stickers, bumper strips, and chances on pizza dinners) administered by parent-teacher organization volunteers. Comprehensive observations were made at three representative schools. Categorization of compliance with safety rules required all passengers to be buckled into safety devices before the children received the rewards. The rewards, on average across schools, increased compliance from baseline of 18.1% to 62.4% during the interventions. Withdrawal of the rewards resulted in a decrease to 49% compliance, but this rate remained above baseline. The involvement of community groups and institutions in this safety program is highlighted.

Accidents, Traffic↗

The relationship of pKa and acute skin irritation in man.

The relationship between pKa and skin irritation in man is studied for a homologous series of benzoic acid derivatives, which permeate through human skin at comparable rates (15-88 micrograms/cm2/hr). Skin irritation and pKa are correlated for pKa less than or equal to 4. Laser Doppler velocimetric assessment of skin blood flow, color meter readings, erythema, edema, and the primary irritation index are all linearly correlated and related to pKa; erythema at 24 hr appears to be the most sensitive parameter to variation in pKa when pKa less than or equal to 4.

Adult↗

Interaction of amiloride and hydrochlorothiazide with atrial natriuretic factor in the medullary collecting duct.

Medullary collecting duct function was studied using the in vivo microcatheterization technique in three groups of rats receiving amiloride, hydrochlorothiazide, or both diuretics. In each group of animals, atrial natriuretic factor (ANF99-126) was given in the second phase of the experiment. The combination of amiloride and hydrochlorothiazide resulted in a more marked natriuresis than either diuretic given as a single agent. Sodium reabsorption in the medullary collecting duct, as a fraction of the delivered load, was reduced from 64% (amiloride) and 69% (hydrochlorothiazide) to 29% (amiloride and hydrochlorothiazide). Atrial natriuretic factor reduced collecting duct sodium reabsorption when added to amiloride or hydrochlorothiazide to 23% and to 41%, respectively, but had no additional effect when given with amiloride and hydrochlorothiazide. Potassium excretion with amiloride and hydrochlorothiazide was intermediate between amiloride or hydrochlorothiazide given as single agents. With the diuretic combination, potassium transport showed no significant reabsorption or secretion along the medullary collecting duct, amiloride was associated with potassium reabsorption, and hydrochlorothiazide was associated with potassium secretion in the duct. The results confirm the importance of the medullary collecting duct as a site of diuretic action. The known additive effects of amiloride and hydrochlorothiazide on sodium excretion and the opposing effects of these agents on potassium excretion occur, to a major degree, in the medullary collecting duct. Furthermore, the additive effects of amiloride and ANF indicate that blocking of amiloride-sensitive sodium channels is not the only mechanism of action of ANF on duct salt transport in vivo.

Amiloride↗

Skull erosion and bony changes in a child with endocardial cushion defect.

A 9-year-old boy with an endocardial cushion defect who had skull erosion as well as widening of the diploe is described. This was accompanied by thickening of the tables, "hair-on-end" striations in the skull, and cortical thinning and medullary cavity expansion in the femora. The skull erosion is attributed to venous distension and increased blood volume. The finding of skull erosion in cyanotic congenital heart disease has not been reported before.

Bone Diseases↗

Inner medullary collecting duct function in ischemic acute renal failure.

Inner medullary collecting duct function in ischemic acute renal failure: The purpose of this study was to determine the role of the medullary collecting duct in the increased urine sodium concentration, decreased urine osmolality, and altered potassium excretion with hyperkalemia which are characteristic of ischemic acute renal failure. Microcatheterization of the inner medullary collecting duct (0.1 to 5 mm from papillary tip) was carried out in rats 24 h after bilateral renal artery clamping for 45 min (n = 8) or sham-operated (n = 8). In ischemic acute renal failure (ARF), tubular fluid osmolality did not increase significantly along the inner medullary collecting duct (IMCD). Tubular fluid sodium concentration was similar to controls at the beginning of the IMCD but was significantly higher at the papillary tip. Tubular fluid to plasma potassium concentration ratio (TF/PK) increased to a greater extent along the IMCD in ischemic ARF than in controls. During acute KCl loading in two additional groups, tubular fluid potassium concentration and TF/PK were much lower at the beginning of the IMCD in ischemic ARF than in controls but increased similarly along the IMCD. In ischemic ARF, with or without KCl loading, renal tissue electrolytes showed reduced potassium concentration in the outer medullary region. The results indicate that impaired IMCD function contributes significantly to the increase in urine sodium concentration and the decrease in urine osmolality which are characteristic of ischemic acute renal failure. In ischemic ARF with mild hyperkalemia, an adaptive increase in K secretion occurred in the IMCD. Severe hyperkalemia and decreased potassium excretion during acute potassium loading in ischemic ARF were determined in more proximal nephron segments and were associated with decreased outer medullary tissue potassium, presumably due to tubular necrosis. Decreased outer medullary tissue potassium could contribute to hyperkalemia by diminishing K secretion in the pars rectae and descending limbs or in the cortical and outer medullary collecting ducts.

Acute Kidney Injury↗

In vivo relationship between transepidermal water loss and percutaneous penetration of some organic compounds in man: effect of anatomic site.

The relationship between the percutaneous penetration of four chemicals and transepidermal water loss (TEWL) was investigated in vivo in man as a function of anatomic site. The findings showed an appreciable difference in the permeability of the skin from one site to another with regard to both water loss and chemical penetration. In addition, independent of the physicochemical properties of the molecules administered, there was a linear relationship between TEWL and penetration. These data confirm both the importance of anatomic site in the degree of permeability of the cutaneous barrier and the utility of determinations of TEWL and percutaneous absorption in the evaluation of its functional condition.

Absorption↗

Effects of amiloride in the medullary collecting duct of rat kidney.

The in vivo microcatheterization technique was used to study amiloride-induced transport alterations in the inner medullary collecting duct. Amiloride treated rats (0.1 mg/hr) had significant diuresis and natriuresis, as well as antikaliuresis, compared to untreated controls. The relative decrease in potassium excretion was associated with a significant rise in plasma potassium concentration. Net sodium transport in the duct was decreased from 83 + 3 to 46 + 6 per cent of delivered load, as a result of amiloride treatment. Smaller, but statistically significant, reductions (P less than 0.01) were seen for fluid and chloride reabsorptions (from 66 + 3 to 51 + 4%, and from 72 + 4 to 52 + 5%, respectively). Potassium reabsorption increased from 15 + 8 to 61 + 6% of delivered load. The data indicated that amiloride natriuresis is determined primarily by inhibition of sodium reabsorption in the medullary collecting duct, probably due to blockade of a specific Na channel. The antikaliuresis, on the other hand, appears to be due to inhibition of secretion both in upstream nephron segments and in the duct itself.

Amiloride↗

Collecting duct function in cis-platinum nephrotoxicity.

Microcatheterization was used to study the effect of cis-platinum nephrotoxicity on inner medullary collecting duct function in anaesthetized rats. Osmolality of collecting duct fluid increased from the beginning to the end (papillary tip) of the collecting duct by only 69 +/- 11 mosmol/kg in cis-platinum treated rats (at 5-6 days) compared with 306 +/- 75 mosmol/kg in sham controls (p less than 0.01). Tubular fluid to plasma inulin concentration ratio was reduced at the beginning and end of the collecting duct. Tubular fluid sodium, chloride, and potassium concentrations were lower at the papillary tip in cis-platinum treated rats (p less than 0.01). The results indicate that collecting duct water reabsorption is reduced, but electrolyte reabsorption is normal (or even increased) in cis-platinum nephrotoxicity. Papillary tissue sodium chloride concentration was reduced in cis-platinum treated rats. We conclude that the characteristic decrease in urine concentrating ability in cis-platinum nephrotoxicity is not primarily the result of an intrinsic abnormality in collecting duct function but is secondary to decreased papillary hypertonicity resulting from impaired function in more proximal nephron segments, presumably the pars recta of the proximal tubule and the loop of Henle where previous studies have demonstrated abnormal function.

Animals↗

Effect of vasopressin analogue (dDAVP) on potassium transport in medullary collecting duct.

The microcatheterization technique was used to examine electrolyte transport in the medullary collecting duct of two groups of anesthetized rats during water diuresis and during a second experimental phase with 1-desamino-8-D-arginine vasopressin (dDAVP) administration or continued water diuresis. Potassium reabsorption of 53-61% of the delivered load was consistently observed in the medullary collecting duct during water diuresis. During dDAVP administration, urinary potassium excretion doubled, and there was no net potassium transport (reabsorption or secretion) in the medullary collecting duct. The change in potassium transport in medullary collecting duct from water diuresis to antidiuresis (dDAVP) was sufficient to account for the increase in urinary potassium excretion. Changes in flow rate, luminal sodium concentration, or collecting duct sodium reabsorption could not account for the changes in potassium transport in the collecting duct during dDAVP. The results are interpreted as indicating that dDAVP stimulates potassium entry (secretion) into the medullary collecting duct, probably by a direct effect. This action of antidiuretic hormone appears to be important in maintaining potassium homeostasis during changing water balance.

Animals↗

Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro.

Human hepatoma cells mimic the acute phase response after treatment with monocyte-conditioned medium. Levels of secreted fibrinogen, alpha-1 acid glycoprotein, C-reactive protein, haptoglobin, and the third component of complement were elevated compared with control levels after 48 h of incubation with conditioned supernatant medium from an enriched fraction of normal peripheral monocytes. Albumin levels declined and alpha-1 antitrypsin remained unchanged. Levels of specific mRNA were measured by hybridization to slot blots and Northern blots and changed in correspondence with protein alterations. Interleukin-1 and tumor necrosis factor stimulated the third component of complement, but did not elevate any other member of the acute phase group and were therefore only partially active in this system. The identification of an in vitro model of the human acute phase response will permit analysis of the molecular basis for coordinate regulation of this group of facultative genes.

C-Reactive Protein↗

Cyclosporine and experimental renal ischemic injury.

To investigate the interaction of cyclosporine nephrotoxicity and renal ischemia, an animal model in rats with bilateral renal artery clamping was used. Rats given cyclosporine had a lower rate of recovery from ischemia. However, the percentages of reduction in glomerular filtration rate in vehicle and cyclosporine groups were the same in sham-operated or ischemically treated group. This suggests a superimposition of cyclosporine nephrotoxicity on the recovering kidneys rather than synergistic potentiation between ischemia and cyclosporine nephrotoxicity.

Animals↗

Effect of acetylcholine and secretin on medullary collecting duct function in the rat.

Microcatheterization was used to study the effect of renal arterial infusion of acetylcholine or secretin on medullary collecting duct function in anaesthetized rats. Acetylcholine infusion was associated with natriuresis and increased sodium delivery to, and decreased reabsorption in, the collecting duct. No changes from control function were found with secretin. Renal blood flow was increased with acetylcholine (+82%, p less than 0.001), but unchanged with secretin (+15%, nonsignificant). We conclude that acetylcholine natriuresis is due to inhibition of tubular reabsorption of sodium in the medullary collecting duct, as well as in upstream nephron segments. While the latter may be hemodynamically mediated, the former indicates a direct transport effect of the hormone in the terminal nephron segment.

Absorption↗

Atrial natriuretic factor inhibits sodium transport in medullary collecting duct.

Characteristics of sodium transport in the inner medullary collecting duct were determined in anesthetized rats before and during intravenous infusion of synthetic atrial natriuretic factor (atriopeptin II). Infusion of the factor was associated with increased sodium delivery and reduced fractional reabsorption in the duct. Increasing delivery to the same extent by KCl infusion had no effect on fractional reabsorption. The results demonstrate that atrial natriuretic factor has a specific inhibitory effect on net sodium transport in this part of the nephron. The mechanism of this inhibition may involve induction of sodium permeability and consequent backflux into the tubular lumen.

Absorption↗

Kinetics and mechanism of hemoglobin denaturation in alkali.

The denaturation of oxy, deoxy, CO and met derivatives of human hemoglobin A at pH 11.7 and 25 degrees C was followed by three assay methods: chromophore absorbance (which indicates changes in the heme), and the amount of precipitation in 24% ammonium sulfate neutral buffer or 0.1 M NaCl neutral buffer (which indicates degree of destabilization of the protein structure). We find that oxyhemoglobin denatures in two parallel reaction sequences. The rate of sequence I is increased when the sulfhydryl groups in the alpha 1 beta 1 subunit interface have been modified by binding p-hydroxymercuribenzoate (which forces monomer formation) and is decreased by the binding of -HgOH (which, unlike the sulfhydryls, is not ionized at pH 11.7). These results support a mechanism in which the net rate of monomer formation is rate limiting and is enhanced in alkali by the ionization of sulfhydryls in the alpha 1 beta 1 subunit interface. In subsequent rapid reactions, ferric hemoglobin and low-salt-precipitable protein are formed. The formation of an oxidant, such as superoxide, is indicated by the kinetics of sulfhydryl oxidation. The same oxidant would be available to initiate the second sequence by oxidizing some of the unreacted oxyhemoglobin to methemoglobin. During methemoglobin denaturation, as in sequence II, a low-salt-soluble ferric hemochrome is formed. In both reactions, this intermediate becomes low-salt-precipitable at the same rate. Deoxyhemoglobin denatures to ferrous hemochrome at the same rate as oxyhemoglobin denaturation in sequence I, and provided oxygen is excluded, the denaturation is fully reversible on neutralization. In the absence of oxygen, CO-hemoglobin does not denature to any detectable extent. The destabilization of hemoglobin structure that was indicated by precipitability occurred only for ferriheme derivatives and was independent of disulfide formation.

Alkalies↗

Skin wound healing determined by water loss.

An in vivo method of monitoring healing was tested incorporating an Evaporimeter measuring water evaporation; reepithelialization was detected through reestablishment of the water barrier. In the first study two wounds were created with a 2-mm biopsy punch on each of the backs of 15 rabbits and covered with occlusive and semiocclusive dressings. Water loss increased from a preoperative value of 6 g m-2 hr-1 to 55 g m-2 hr-1 after surgery. Water loss from the occluded site returned to baseline values in 9 days as opposed to 17 days for the semioccluded sites (P less than 0.05). The second study followed the healing of full-thickness 4 X 4-cm wounds in five rabbits treated with fine-mesh gauze and five treated with a human amnion dressing. Wound area and water loss were observed during the repair process. Visually measuring the wound area, the injuries appeared 100% healed on Day 30. The Evaporimeter continued to detect significantly increased water loss up until Day 45 when the original baseline values were reached. No differences were observed between the gauze and amnion groups. The Evaporimeter presents a simple yet accurate, noninvasive tool measuring the wound healing endpoint based on regeneration of the epidermal water barrier.

Animals↗