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Biomedical subjects

D W Seldin

Publications and source records attributed to D W Seldin.

At least 55 records · Page 3Linked to original sources
PubMed1985

Effect of soft-tissue pathology on detection of pedal osteomyelitis in diabetics.

Three-phase bone scans were performed on 30 diabetic patients suspected of having acute pedal osteomyelitis; 23 also had a pedal ulcer, seven had coexisting cellulitis, and 14 had diminished pedal pulses. Fifteen patients were receiving antibiotics at the time of the scan. A tissue diagnosis was available in 18 patients and 12 had no clinical evidence of infection on follow-up. Focal arterial hyperemia combined with focally increased activity on blood-pool and delayed (2-3 hr) scans were interpreted as acute osteomyelitis. Scans showing venous hyperemia were interpreted as soft-tissue pathology without acute osteomyelitis. Companion radiographs were reviewed independently. The sensitivity and specificity of the scans for osteomyelitis were 0.94 and 0.79, respectively, while radiographic sensitivity was 0.93 and specificity was 0.50. The presence of soft-tissue ulcers or cellulitis, peripheral vascular disease, or recent antibiotic therapy had no significant adverse effect on the accuracy of the three-phase scan in diagnosing osteomyelitis.

Adult↗
PubMed1984

Transient focal liver scan defects in children receiving chemotherapy (pseudometastases). Work in progress.

Three pediatric patients with tumors (two rhabdomyosarcoma, one Wilms tumor) had significant focal defects on Tc-99m sulfur colloid scans while receiving chemotherapy (all three had received chemotherapy, including actinomycin D, within ten days prior to scanning). In all three, the defects resolved spontaneously; one biopsy showed fibrosis of a mild degree. The finding of defects on liver scans of pediatric patients receiving chemotherapy must not be automatically assumed to be metastatic disease; the changes may relate to hepatic response to recently administered chemotherapy.

Child↗
PubMed1983

The diagnostic approach to ectopic ureterocele and the renal duplication complex.

The child with ectopic ureterocele frequently presents a diagnostic challenge. The use of standard excretory urography combined with newer modalities, such as ultrasonography and radionuclide renal scanning, provides an orderly diagnostic approach to ectopic ureterocele. This integrated approach should ensure the highest yield in a diagnostic sense and aid in assessing upper tract function, thus, helping with the selection of the proper surgical management.

Child, Preschool↗
PubMed1983

Serial lung scintigraphy: utility in diagnosis of pulmonary embolism.

Pairs of sequential perfusion lung scans and pulmonary angiograms obtained in 45 patients were reviewed to investigate the utility of short-term, sequential scintigraphy in the diagnosis of pulmonary embolism (PE). Forty-six sequential scan pairs were reviewed; 13 were ventilation-perfusion (V-P) pairs. Angiograms were obtained within 48 hours of either the first (65%) or second (35%) perfusion scan in each pair. Sequential scintigraphic patterns were classified as showing change (i.e., improvement in defects, new defects), no change, or as being indeterminate. A changing perfusion pattern was associated with a high (20/23) likelihood of PE, but seven of 16 patients with stable perfusion patterns also had PE. The sensitivity of a changing perfusion pattern for PE was 0.74 (20/27) and its specificity was 0.75 (9/12). In two of six patients who had serial V-P studies that showed changing perfusion defects, there were matched changes in regional ventilation and angiograms were negative. The findings suggest that short-term serial perfusion lung scanning may aid the scintigraphic diagnosis of PE in certain circumstances. Serial V-P imaging is needed, however, to maximize diagnostic specificity.

Adult↗
PubMed1983

Left ventricular volume determined from scintigraphy and digital angiography by a semi-automated geometric method.

The utility of a semi-automatic method of measuring left ventricular (LV) volume geometrically from gated blood-pool studies and digital subtraction angiography (DSA) was investigated using computerized edge detection and spatial calibration algorithms. LAO LV volumes determined from gated blood-pool studies were compared to volumes obtained from contrast left ventriculograms in 21 patients and the applicability of this method to DSA was evaluated in 25 additional patients who also had conventional left ventriculography. There was excellent correlation between the two, both for radionuclide studies and for DSA. Computer-based geometric determinations of LV volume appear to be rapid, accurate, and less dependent on subjective operator decisions than previously reported geometric approaches.

Adult↗
PubMed1983

On the generation, maintenance, and correction of metabolic alkalosis.

The study of derangements in salt, water, and acid-base homeostasis frequently reveals much about renal transport mechanisms and their regulation. The study of one such derangement, metabolic alkalosis, has played a special role in contributing to our knowledge of renal function. Elucidation of the kidney's role in the generation, maintenance, and correction of metabolic alkalosis has provided information about proximal tubule transport and its response to volume contraction, volume expansion, and K depletion. Also, distal nephron transport and its response to mineralocorticoids and dietary anion composition has been clarified by studies on metabolic alkalosis. Finally, we have learned about the importance of Na delivery to distal nephron sites and the avidity with which these distal nephron sites reabsorb sodium. Indeed, reviews on the subject of metabolic alkalosis have presented thorough and convincing physiologic arguments on how the kidney helps to generate and maintain this derangement in acid-base balance. However, more recent experimental work has led some to reconsider how the kidney functions in metabolic alkalosis. In an earlier paper in this journal [Am. J. Physiol. 244 (Renal Fluid Electrolyte Physiol. 13): F217-F221, 1983], Galla, Bonduris, and Luke present an argument for the correction of chloride-depletion alkalosis in the rat without volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1983

Anion dependence of rabbit medullary collecting duct acidification.

Rabbit medullary collecting duct (MCD) acidification has been demonstrated to occur by means of a sodium-independent, aldosterone-stimulated mechanism. We have examined the anionic dependence of this process by means of the isolated perfused tubule technique. Total replacement of perfusate chloride with gluconate enhanced tubular bicarbonate reabsorption (JHCO3), from a basal rate of 10.7 +/- 1.0 pmol X mm-1 X min-1 to a rate of 15.01 +/- 1.0 pmol X mm-1 X min-1. Removal of bath chloride, with and without removal of perfusate chloride completely abolished acidification. Bath, but not luminal 4-acetamido-4' isothiocyano-2,2'-disulfonic stilbene provoked a marked decrease in JHCO3 from 10.1 +/- 1.2 pmol X mm-1 X min-1 to 2.3 +/- 0.3 pmol X mm-1 X min-1. Measurement of chloride reabsorptive rate (JCl) revealed colinearity between JHCO3 (9.18 +/- 0.9 pmol X mm-1 X min-1) and JCl (9.75 +/- 1.18 pmol X mm-1 X min-1). We propose a model of mammalian distal nephron acidification in which (a) cellular base exit is effected by means of a basolateral membrane Cl-base exchanger and (b) net electroneutrality of electrogenic proton secretion is maintained by the parallel movement of an anionic species, functionally chloride.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1983

Mineralocorticoid modulation of rabbit medullary collecting duct acidification. A sodium-independent effect.

Rabbit medullary collecting duct (MCD) from inner stripe of outer medulla has been identified as a major distal nephron acidification site. The isolated, perfused tubule technique was used to examine the roles of mineralocorticoid and glucocorticoid in regulation of MCD acidification. Surgical adrenalectomy reduced bicarbonate reabsorptive rate (JHCO3, pmol X mm-1 X min-1) from the normal of 9.79 +/- 1.21 to 0.67 +/- 1.1. Chronic administration of deoxycorticosterone acetate (DOCA) increased JHCO3 of MCD significantly to 18.02 +/- 1.62 whereas chronic dexamethasone administration did not affect JHCO3. The direct effects of aldosterone and dexamethasone upon MCD acidification were examined by perfusing tubules harvested from adrenalectomized rabbits in the presence of aldosterone or dexamethasone. Aldosterone, at 5 X 10(-8) M, increased JHCO3 significantly from 1.27 +/- 0.28 to 3.09 +/- 0.34. At 10(-6) M, aldosterone produced a greater increase in JHCO3 from 0.67 +/- 1.1 to 9.39 +/- 1.59. In vitro dexamethasone treatment had no effect on JHCO3. Studies examining the sodium dependence of aldosterone-stimulated acidification demonstrated that JHCO3 in tubules harvested from normal and deoxycorticosterone acetate-treated animals was unaffected by total replacement of sodium with tetramethylammonium. Likewise, luminal amiloride (5 X 10(-5) M) had no effect on JHCO3 in tubules harvested from adrenalectomized and normal animals. Moreover, the acute, in vitro stimulatory effect of aldosterone was seen to occur in the presence of luminal amiloride. These studies define a mammalian distal nephron segment that possesses major acidifying capacity, which is modulated by mineralocorticoid but independent of luminal sodium.

Absorption↗
PubMed1982

Spatial calibration of digital scintigraphic images: work in progress.

Accurate scintigraphic determination of organ dimensions is often difficult because of the wide variety of camera-collimator combinations and display formats used for imaging. An algorithm (SPACE-CAL) was developed for digital spatial calibration of up to six large- or small-field gamma cameras using various collimators and magnification factors. The algorithm employs a master calibration file that can be used at multiple terminals. An interactive subroutine permits the operator to measure distances and areas directly from the images. Evaluation of three operators' measurements of a pine-tree phantom acquired at various magnifications showed that distances could be measured with a high degree of accuracy. Calculation of ejection fraction from end-diastolic and end-systolic areas determined by SPACE-CAL showed a high correlation with automatic count determinations (r = 0.96) and angiographic calculations (r = 0.93) of ejection fraction in 12 patients. SPACE-CAL provides an easily implemented, reproducible, and rapid method for accurate analysis of organ dimensions in digital images.

Computers↗
PubMed1982

Lack of solvent drag of NaCl and NaHCO3 in rabbit proximal tubules.

Using in vitro microperfusion of rabbit nephron segments we measured the effects of osmotically induced water flow on net transport of HCO3 and Cl. Measurements were made in superficial and juxtamedullary proximal convolutions and in superficial pars recta. In addition, measurements were taken in the presence and absence (hypothermia) of active transport. Using osmotic gradients of 25 mM raffinose in superficial and 50 mM in juxtamedullary segments, we observed increases in water flow equal to or greater than the normal rates of volume reabsorption observed in these tubule segments. However, there were no significant changes in HCO3 and Cl flux. This lack of significant solvent drag was seen both when osmotic water flow was in the lumen-to-bath direction and when osmotic flow was in the bath-to-lumen direction. The results of these studies suggest that solvent drag does not contribute significantly to NaCl and NaHCO3 reabsorption in proximal tubules. The lack of significant solvent drag of these salts can be interpreted as indicating either that osmotically induced transepithelial water flow in proximal tubules almost exclusively traverses transcellular pathways or that proximal tubule tight junction reflection coefficients for these salts are close to unity.

Animals↗
PubMed1982

Dietary modulation of active potassium secretion in the cortical collecting tubule of adrenalectomized rabbits.

Addisonian patients can maintain potassium homeostasis despite the absence of mineralocorticoid. The present in vitro microperfusion studies examine what role the cortical collecting tubule might play in this process. All studies were performed on tubules harvested from adrenalectomized rabbits, which were maintained on 0.15 M NaCl drinking water and dexamethasone 50 mug/d. Perfusion and bath solutions were symmetrical Ringer's bicarbonate with [K] of 5 meq/liter. Initial studies on cortical collecting tubules from adrenalectomized animals ingesting a high potassium chow (9 meq K/kg body wt) demonstrated net potassium secretion against an electrochemical gradient (mean collected fluid [K] 16.5+/-2.6 meq/liter with an observed transepithelial voltage of -6.3+/-4.1 mV; predicted voltage for passive distribution of potassium being -28.2 mV). To examine whether this active potassium secretion could be modulated by dietary potassium, independent of mineralocorticoid, two diets identical in all respects except for potassium content were formulated. Potassium secretion was compared in cortical collecting tubules harvested from adrenalectomized animals on low (0.1 meq K) and high (10 meq K) potassium intake. Mean net potassium secretion by cortical collecting tubules was 2.02+/-0.54 peq mm(-1) min(-1) in the low potassium diet group and 5.34+/-.74 peq.mm(-1).min(-1) in the high potassium group. The mean transepithelial voltages of the collecting tubules did not differ between the two dietary groups. While net Na reabsorption was significantly greater in tubules from the high K group, this could not account for the differences in K secretion. These data demonstrate that: (a) the cortical collecting tubule can actively secrete potassium and that the magnitude of this potassium secretion correlates with potassium intake; (b) this active potassium secretory process in independent of mineralocorticoid. These findings support the hypothesis that the cortical collecting tubule may contribute to K homeostasis in Addison's disease.

Addison Disease↗
PubMed1979

Microelectrode determination of pH and PCO2 in rat proximal tubule after benzolamide: evidence for hydrogen ion secretion.

Previous micropuncture studies supporting hydrogen secretion as the mechanism of bicarbonate reabsorption have relied on the demonstration of an acid disequilibrium pH in the proximal tubule after systemic administration of a carbonic anhydrase inhibitor. Previous calculations of disequilibrium pH, however, have involved the necessary assumption that PCO2 in the proximal convoluted tubule was equal to arterial blood PCO2. This assumption can no longer be supported in view of the recent demonstration that the PCO2 in proximal and distal tubular fluid exceeded arterial blood by approximately 25 mm Hg. The purpose of the present study was to determine directly pH and PCO2 with microelectrodes in both the early and late segments of the accessible proximal tubule of nine Sprague-Dawley rats before and after administration of benzolamide (2.0 mg/kg/hr, i.v.). In the early proximal tubule, pH decreased significantly after benzolamide administration from 6.98 +/- 0.03 to 6.62 +/- 0.03 pH U (P less than 0.001), and PCO2 also decreased from 65.1 +/- 1.2 to 59.3 +/- 1.4 mm Hg (P less than 0.005). In the late proximal convoluted tubule, pH did not change after benzolamide (6.75 +/- 0.02 to 6.77 +/- 0.02), but PCO2 decreased significantly (64.3 +/- 1.5 to 57.7 +/- 1.6) (P less than 0.01). We conclude: (1) the fall in both pH and PCO2 in the early proximal tubule indicates that carbonic acid, not carbon dioxide accumulates after inhibition of luminal carbonic anhydrase; (2) although PCO2 also decreased in the late proximal tubule, unlike the early segment, pH was unchanged after benzolamide administration, perhaps as a result of increased bicarbonate delivery; and (3) PCO2 in vivo was significantly greater than was systemic arterial PCO2 before and after benzolamide administration in both the early and late proximal convoluted tubule. These findings lend support to the view that bicarbonate reabsorption in the proximal convoluted tubule occurs, in part, by hydrogen secretion.

Animals↗
PubMed1978

Disturbances in acid-base balance during hypophosphatemia and phosphate depletion.

Phosphate depletion leads to bone resorption, resulting in the accession of alkali to the blood and urine. There may also be a release of lactic acid from liver, resulting from ATP depletion and intracellular alkalosis. In general, the net result of these tissue effects is an alkali load discharged into the extracellular fluid. In the kidneys, phosphate depletion causes impaired proximal tubular reabsorption of bicarbonate, and perhaps other substrates, owing in all likelihood to both intracellular alkalosis and depletion of ATP. This impaired proximal capacity to reclaim bicarbonate results in hyperchloremic acidosis. The distal nephron may contribute to acidosis by virtue of inability to produce titratable acid (phosphate-free urine) and perhaps impaired ammonia production. Severe phosphate depletion, therefore, tends to produce hyperchloremic acidosis as a result of a diminished capacity for bicarbonate reclamation in the proximal tubule and probably some impairment of bicarbonate regeneration in the distal nephron. These effects, when marked, ultimately outweigh the contribution of alkali coming from bone breakdown. In the liver, phosphate depletion may stimulate lactic acid production by reducing hepatic ATP stores (Pasteur effect) and producing intracellular alkalosis. ATP depletion may also limit hepatic uptake of lactate. Finally, in muscle cells ATP depletion, resulting from either profound hypophosphatemia or the metabolism of massive fructose loads, may eventuate in frank rhabdomyolysis.

Acid-Base Imbalance↗
PubMed1978

Direct determination of PCO2 in the rat renal cortex.

The mechanism by which the kidney reabsorbs sodium bicarbonate could be a result of (a) H+ secretion, (b) direct HCO3- reabsorption, or (c) a combination of both processes. Most of the studies which have supported the H+ secretory theory have involved the assumption that tubular fluid and arterial PCO2 were equal. We have utilized a new PCO2 microelectrode to directly determine in situ PCO2 of tubular fluid and stellate vessel blood in the cortex of the rat kidney during control conditions and after alterations in acid-base status. In 21 control rats, proximal tubular fluid PCO2 exceeded systemic arterial PCO2 (deltaCO2) by 25.9 +/- 0.92 mm Hg (P less than 0.001). The values obtained for both distal tubular fluid and stellate vessel blood were not significantly different from proximal tubular PCO2. Evaluation of PCO2 in the proximal tubules of Munich-Wistar rats did not reveal evidence for a declining profile for PCO2 along the length of the nephron. When proximal bicarbonate reabsorption was increased or decreased acutely by alterations in acid-base status, deltaPCO2 changed in paralle. Furthermore, benzolamide administration significantly reduced deltaPCO2. We conclude: (a) that the PCO2 in tubular fluid is significantly greater than systemic arterial PCO2, (b) that there is no tendency for the observed PCO2 to fall along the proximal tubule, (c) the mean PCO2 in the proximal and distal tubules as well as the stellate vessle is not significantly different, thereby rendering the concept of a "diffusion barrier" for CO2 in the proximal tubule unlikely, and (d) the level of renal cortical PCO2 appears to vary directly with the magnitude of bicarbonate reabsorption.

Absorption↗
PubMed1977

Effect of perfusion rate on the fluxes of water, sodium, chloride and urea across the proximal convoluted tubule.

Studies were undertaken to examine the mechanism whereby changes in intraluminal flow rates after reabsorption in the isolated perfused proximal tubule of the rabbit. All protocols employed the technique of in vitro perfusion of isolated segments of the proximal convoluted tubule. Stepwise elimination of d-glucose and l-alanine from an artifical perfusate stimulating ultrafiltrate decreased the unidirectional flux of sodium, transtubular potential difference, and net water absorption. Using isosmolal ultrafiltrate as the perfusate, net fluid reabsorption and the unidirectional lumen-to-bath flux of sodium and chloride decreased with a decrease in flow rate below 11 nl/min, but neither net fluid reabsorption nor the unidirectional fluxes of sodium and chloride increased further as the perfusion rate was increased above 11 nl/min. The unidirectional flux of 14C-urea was not affected by changes of perfusion rate from 1.6 to 44 nl/min. The dependence of net fluid reabsorption and unidirectional fluxes of sodium and chloride on flow rate per se, and not on intraluminal hydrostatic pressure or geometry, was established by demonstrating their decrease despite a rise in intraluminal pressure and inside diameter produced by counterpressure at the collecting end of the tubule, while flow was decreased. Ouabain decreased net fluid reabsorption to near zero at all flow rates, but ouabain had no effect on the flow-dependency of unidirectional sodium anf sodium was eliminated with a decrease in bicarbonate concentration and removal of d-glucose and l-alanine from the perfusate. Thus, the present studies demonstrate that net water and unidirectional sodium and chloride fluxes are flow-dependent. At flow rates somewhere below 11 nl/min, unidirectional fluxes decreased with decreasing perfusion rates; however, at perfusion rates greater than 11 nl/min, there was no further effect of perfusion rate on either net water absorption or the unidirectional fluxes of sodium or chloride. These effects may be partly mediated through the flow-dependent changes in the intraluminal concentration of bicarbonate, d-glucose, and 1-alanine.

Adsorption↗