Striatal dopamine release tracks the relationship between actions and their consequences.

The acquisition and performance of goal-directed actions has long been argued to depend on the integration of glutamatergic inputs to the posterior dorsomedial striatum (pDMS) under the modulatory influence of dopamine. Nevertheless, relatively little is known about the dynamics of striatal dopamine during goal-directed actions. To investigate this, we chronically recorded dopamine release in the pDMS as rats acquired two actions for distinct outcomes as these action-outcome associations were incremented and then subsequently degraded or reversed. We found that bilateral dopamine release scaled with action value, whereas the lateralized dopamine signal, i.e., the difference in dopamine release ipsilaterally and contralaterally to the direction of the goal-directed action, reflected the strength of the action-outcome association independently of changes in movement. Our results establish, therefore, that striatal dopamine activity during goal-directed action reflects both bilateral moment-to-moment changes in action value and the long-term action-outcome association.

Role of the eosinophil in chronic vascular rejection of renal allografts.

Obiliterative arteriopathy in chronic renal allograft rejection is caused by intimal smooth muscle proliferation accompanied by infiltration of lymphocytes, monocytes, and eosinophils. We investigated the role of the eosinophil in chronic rejection. Twenty-four allograft nephrectomies were examined for the presence of eosinophils on hematoxylin-eosin-stained sections and using epifluorescence on Fisher-Giemsa-stained sections. Among 15 cases with chronic rejection, eosinophils were detected in 14 cases (93%) with epifluorescence compared with only six cases (40%) with hematoxylin-eosin staining (P = 0.005). With epifluorescence, eosinophils were identified in the intimal, adventitial, and tubulointerstitial compartments in 73%, 80%, and 87% of cases, respectively. To examine the pathogenic relevance of the eosinophils in the vessel wall, we investigated the effect of eosinophil-conditioned medium on DNA synthesis in cultured vascular smooth muscle cells. Autofluorescent eosinophils were isolated from atopic human donors using a fluorescence-activated cell sorter. Supernatant was collected from eosinophils (1 x 10(6)/mL) cultured overnight in medium with 0.5% fetal bovine serum. Incorporation of 3H-thymidine into DNA was measured in rat and human vascular smooth muscle cells treated for 24 hours with eosinophil-conditioned medium at 1:20, 1:10, 1:5, and 1:2 dilutions. Eosinophil-conditioned medium had a significant dose-dependent stimulatory effect on DNA synthesis in both cell lines. Our results indicate that eosinophil involvement in chronic renal allograft rejection is more common than previously recognized. The stimulatory effect of eosinophil-conditioned medium on vascular smooth muscle cell DNA synthesis suggests that eosinophils may be involved in the pathogenesis of the obliterative arteriopathy characteristically seen in chronic vascular rejection of renal allografts.

Aluminum and lead absorption from dietary sources in women ingesting calcium citrate.

Animal models suggest that citrate-containing compounds augment absorption of aluminum from food and tap water, causing aluminum accumulation in bone and brain despite normal renal function. Citrate also enhances lead absorption in animals. We questioned whether use of calcium citrate by women as a calcium supplement causes an increase in aluminum or lead absorption from dietary sources. Changes in 24-hour urine aluminum and lead excretion, plasma aluminum level, and whole blood lead level were assessed in 30 healthy women before and during treatment with calcium citrate (800 mg of elemental calcium per day). During calcium citrate therapy, urinary aluminum excretion and plasma aluminum level increased significantly. In contrast, there were no changes in urine or whole blood lead levels. We conclude that treatment with calcium citrate significantly increases absorption of aluminum from dietary sources. Additional studies are needed to determine whether long-term use of calcium citrate leads to aluminum accumulation and toxicity.

Forty-five year follow-up after uninephrectomy.

This study examined the consequences of nephrectomy in United States Army personnel who lost a kidney due to trauma during World War II (WWII). Records of 62 servicemen who underwent nephrectomy at an average age of 25 years were obtained. Mortality was compared with that of WWII servicemen of the same age. Medical records of 28 deceased subjects were reviewed for evidence of kidney disease. Medical histories were obtained and blood pressure and kidney function were assessed in 28 living subjects. Two subjects could not be located, and four subjects declined to participate. Mortality at 45 years was not increased in nephrectomized subjects. Kidney disease present in six of 28 deceased subjects was attributable to causes other than prior nephrectomy. Glomerular sclerosis was not increased in 10 subjects who had autopsy examinations. The prevalence of hypertension was not increased in living subjects. Five of 28 living subjects had abnormal renal function manifested by proteinuria greater than 250 mg/day in four cases (range: 377 to 535 mg/day) and serum creatinine levels greater than 1.5 mg/dl in three cases (range: 1.7 to 1.9 mg/dl). Conditions other than nephrectomy could have contributed to impairment of renal function in each of these subjects. These findings suggest that uninephrectomy in young adults has few major adverse consequences over 45 years.

Calcium acetate control of serum phosphorus in hemodialysis patients.

Calcium acetate has many characteristics of an ideal phosphorus binder. It is a readily soluble salt that avidly binds phosphorus in vitro at pH 5 and above. One-dose/one-meal balance studies show it to be more potent than calcium carbonate or calcium citrate. We studied chronic (3-month) phosphorus binding with calcium acetate in 91 hyperphosphatemic dialysis patients at four different centers. All phosphorus binders were stopped for 2 weeks. Calcium acetate at an initial dose of 8.11 mmol (325 mg Ca2+) per meal was then used as the only phosphorus binder. Dose was adjusted to attempt control of predialysis phosphorus level less than 1.78 mmol/L (5.5 mg/100 mL). Final calcium acetate dose was 14.6 mmol (586 mg) Ca2+ per meal. Sixteen patients developed mild transient hypercalcemia (mean, 2.84 mmol/L [11.4 mg/dL]. Initial phosphorus values in mmol/L (mg/dL) were 2.39 (7.4); at 1 month, 1.91 (5.9); and at 3 months, 1.68 (5.2). Initial calcium values in mmol/L (mg/dL) were 2.22 (8.9); at 1 month, 2.37 (9.5); and at 3 months, 2.42 (9.7). Initial aluminum values in mumol/L (micrograms/L) were 2.99 (80.7); and at 3 months were 2.54 (68.4). Initial C-terminal parathyroid hormone (C-PTH) values in ng/mL were 14.6; at 1 month, 11.9; and at 3 months, 13.2. Sixty-nine patients then entered a double-blind study. Phosphorus binders were stopped for 1 week. Calcium acetate (at a dose established in a prior study) or placebo was then administered for 2 weeks. Next, patients were crossed to the opposite regimen for 2 weeks. Initial phosphorus was 2.36 mmol/L (7.3 mg/100 mL) and calcium 2.22 mmol/L (8.9 mg/100 mL).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of calcium acetate or calcium citrate on intestinal aluminum absorption.

The risk of aluminum (Al) accumulation in patients with chronic renal failure has led to use of non-Al phosphate binders. Frequently, Al and non-Al phosphate binders are co-administered. Unfortunately, calcium citrate (Ca citr), when given with Al-gel, markedly enhances Al absorption. To determine whether calcium acetate (Ca acetate) also augments Al absorption, 10 normal volunteers were each given orally, three-day courses of the following drug combinations dosed four times daily: 1) aluminum hydroxide gel (Al[OH]3) (5 ml) alone; 2) Al[OH]3 (5 ml) plus Ca acetate (1330 mg); 3) Al[OH]3 (5 ml) plus Ca citr (950 mg). A nine day wash-out occurred between each course. Al levels were measured using flameless atomic absorption spectrophotometry. Daily urine Al excretion was measured during a two-day baseline before each course and during each three-day drug course. Plasma Al was obtained during each baseline and drug course. Mean 24-hour Al excretion (micrograms/g creatinine/day) at baseline versus treatment for each combination was: 1) 5.9 +/- 3.2 versus 42.0 +/- 40.7 (mean +/- SD); 2) 5.7 +/- 3.0 versus 40.3 +/- 28.6: 3) 6.3 +/- 3.4 versus 175.8 +/- 103.3. Al excretion was significantly greater with combination 3 than with either 1 or 2 (P less than 0.05). The difference between 1 and 2 was not significant. Plasma Al (micrograms/liter) at baseline versus treatment for each combination was: 1) 5.3 +/- 4.2 versus 8.1 +/- 2.5 (mean +/- SD); 2) 3.1 +/- 2.2 versus 7.3 +/- 2.9; 3) 3.0 +/- 2.3 versus 12.0 +/- 6.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of antihypertensive effect of potassium depletion in renovascular hypertension.

K depletion (KD) prevents the development of hypertension in two-kidney, one-clip renovascular, hypertension [mean arterial pressure: 110 +/- 5 (KD) vs. 142 +/- 3 mmHg in potassium replete (KR); P less than 0.001]. The protective effect of KD is associated with a 60% decrease in angiotensin II (ANG II) pressor responsiveness and a 40% decrease in ANG II binding to mesenteric artery particles from rats with renovascular hypertension (receptor number 117 +/- 16 in KD vs. 165 +/- 14 fmol/mg protein in KR, P less than 0.05). To determine whether decreases in binding could account for decreases in ANG II pressor responsivity, we measured ANG II binding after bilateral nephrectomy or sustained administration of converting-enzyme inhibitor. Both maneuvers resulted in increases in binding, such that total binding and receptor number were greater than in comparably treated KR rats; e.g., after nephrectomy, receptor number was 215 +/- 26 in KD vs. 98 +/- 12 fmol/mg protein in KR, (P less than 0.01). Despite increased binding, the pressor response to ANG II in KD rats, which were nephrectomized or treated with converting-enzyme inhibitor, was still reduced by 50% compared with comparably treated KR rats. To determine whether the decreased ANG II pressor responsivity of KD was caused by cellular K depletion or to increases in ANG H induced by KD, we administered K to KD, ANG II-deficient rats. ANG II pressor responsivity increased, and total binding and receptor number decreased (KD, ANG II- deficient 246 +/ 22 fmol/mg protein; KD, ANG II-deficient + K 91 +/ 16 fmol/mg protein; P less than 0.005) with K.(ABSTRACT TRUNCATED AT 250 WORDS)

Eosinophiluria.

Hansel's stain is a simple technique that can easily be performed in a clinical or office setting. It allows for improved detection of the eosinophiluria when compared with conventional Wright's stain. The mechanism underlying the superiority of the Hansel's stain remains to be elucidated. Eosinophiluria demonstrated by Hansel's stain appears to be a sensitive marker for drug-induced acute interstitial nephritis and probably allows differentiation from acute tubular necrosis. However, the spectrum of eosinophiluria also includes acute glomerulonephritis, rapidly progressive glomerulonephritis, prostatitis, and urinary tract obstruction. Therefore, the finding of eosinophiluria on Hansel's stain clearly cannot be considered diagnostic of acute interstitial nephritis. In the absence of renal biopsy or other clinical clues to suggest the diagnosis, eosinophiluria should not be used as the sole criterion for the diagnosis of acute interstitial nephritis or a a justification for empiric steroid therapy.

Eosinophiluria--a new method of detection and definition of the clinical spectrum.

Eosinophiluria is considered a useful marker of drug-induced acute interstitial nephritis. However, recognition of eosinophiluria by Wright's staining is technically difficult, and the spectrum of disorders causing eosinophiluria is not completely defined. We have adapted Hansel's stain for the examination of urinary sediment. Whereas there was a variable uptake of Wright's stain by eosinophils in the urine, such eosinophils were readily recognized with Hansel's stain by the presence of bright red granules. The prevalence of eosinophiluria in acute interstitial nephritis was 10 of 11 patients, in acute tubular necrosis none of 30, in acute pyelonephritis none of 10, in acute cystitis 1 of 15, in postinfectious glomerulonephritis 1 of 6, in rapidly progressive glomerulonephritis 4 of 10, and in acute prostatitis 6 of 10. Eosinophiluria in acute interstitial nephritis was demonstrated by Hansel's stain in 10 of 11 patients but by Wright's stain in only 2 of 11 patients. We conclude that Hansel's stain substantially improves the recognition of eosinophiluria as compared with Wright's stain. Eosinophiluria is useful in distinguishing acute interstitial nephritis from acute tubular necrosis. The clinical spectrum of eosinophiluria also includes rapidly progressive glomerulonephritis, acute prostatitis, and occasionally, acute cystitis or postinfectious glomerulonephritis.