Showing papers by "Veterans Health Administration published in 1980"
Journal Article•
TL;DR: It is concluded that at least some non-small-cell lung cancers have a much less stringent growth factor requirement for establishment, have higher cloning efficiencies, and lack APUD cell properties.
Abstract: Small-cell carcinoma of the lung (SCCL) grows rapidly in patients and can be maintained in culture for months but is difficult to establish in continuously replicating, clonable cell lines. We have established 15 SCCL cell lines from 11 patients. The SCCL lines grew as floating-cell aggregates with relatively long doubling times and formed tumors having typical SCCL histology in athymic nude mice. They had human enzyme markers, were aneuploid, and cloned in soft agarose at low efficiencies. These lines and their clonal derivatives expressed features of amine precursor uptake and decarboxylation (APUD) cells, including high dopa decarboxylase activity (EC 4.1.1.28), formaldehyde-induced fluorescence, and neurosecretory granules. While only two of 21 tumor specimens plated in fetal bovine serum-supplemented medium (growth medium) developed into continuous lines, 6 of 11 tumor specimens plated into growth medium conditioned by other SCCL cultures developed into lines. Conditioned medium also increased the colony-forming efficiency and colony size of some primary tumor specimens and early unestablished cultures, including one of the two specimens not absolutely requiring conditioned medium for initial growth. Continuous cell lines were eventually established from all eight SCCL tumors heterotransplanted in athymic nude mice; however, their replication was initially dependent on the presence of mouse stromal cell for periods of 3 to 24 months. Growth factor requirements of lung tumors of other histologies appeared less stringent; three of five non-SCCL lung tumors were readily established as continuous cell lines in growth medium. These cell lines from non-SCCL lung cancers lacked the APUD properties and neurosecretory granules characteristic of SCCL. We conclude that (a) human small-cell lung cancer lines and their clonal derivatives grown in vitro for long periods of time continue to express a program for APUD cell properties; (b) the establishment of such lines in some cases stringently requires, and in other cases is greatly facilitated by, conditioned medium containing as yet unknown growth factors; (c) these factors can come from either other cell cultures or nude mouse tumor stromal cells; and (d) that at least some non-small-cell lung cancers have a much less stringent growth factor requirement for establishment, have higher cloning efficiencies, and lack APUD cell properties.
331 citations
TL;DR: It is concluded that prolonged cigarette smoking is associated with progressive pathologic changes in the small airways that may be an important cause of airflow obstruction and that may predispose to the development of centrilobular emphysema.
Abstract: We studied lungs from 25 smokers and 14 lifelong nonsmokers, all over 40 yr of age, to examine the relationship of long-term cigarette smoking to histopathologic changes in the small airways Despite considerable overlap between the 2 groups, smokers had a significantly higher score (p < 001) for small airway disease The specific morphologic features separating smokers from nonsmokers were increases in goblet cell metaplasia (p < 0001), smooth muscle hypertrophy (p < 005), inflammation in the walls of bronchioles (p < 001), and respiratory bronchiolitis (p < 0001) The average bronchiolar diameter was not significantly different in smokers compared with nonsmokers; however, smokers had an excess of airways less than 400 microns in diameter (p < 003) Among smokers, the severity of small airway disease correlated with the percentage of airways that are less than 400 microns in diameter (rs = 063) and with the extent of centrilobular emphysema (r = 053) Smokers also had an increase in the proportion of bronchial gland mass (p < 005), but this pathologic feature was not related to the severity of either small airway disease or centrilobular emphysema We concluded that prolonged cigarette smoking is associated with progressive pathologic changes in the small airways that may be an important cause of airflow obstruction and that may predispose to the development of centrilobular emphysema
292 citations
Journal Article•
TL;DR: The results suggest that the known inhibitory effects of ethanol and pentobarbital on the stimulated release of neurotransmitters and the development of tolerance of these effects may be mediated by the inhibition of the depolarization-dependent influx of calcium by these drugs.
Abstract: In vitro addition of ethanol or pentobarbital to synaptosomes isolated from rat or mouse brain inhibited the depolarization-dependent uptake of calcium without affecting uptake under nondepolarizing conditions. Ethanol inhibited the uptake in a concentration-dependent manner over the range of 45 to 720 mM. Analysis of the effects of ethanol and pentobarbital on calcium uptake at different temperatures indicated that the drugs did not change the activation energy of the process but shifted the Arrhenius curves toward higher temperatures. Synaptosomes isolated from mice chronically ingesting ethanol were found to be tolerant to the inhibitory effects of ethanol and pentobarbital but not tolerant to the inhibitory effects of acetaldehyde. Synaptosomes from ethanol tolerant-dependent mice accumulated less calcium in the absence of ethanol than did synaptosomes from control mice. This depression of uptake was reversed by in vitro exposure of the synaptosomes to a low concentration of ethanol, suggesting that it represents a biochemical response to withdrawal of alcohol. A single acute injection of ethanol 1 hr before sacrifice did not alter the calcium uptake activity or the drug sensitivity of the synaptosomes. These results suggest that the known inhibitory effects of ethanol and pentobarbital on the stimulated release of neurotransmitters and the development of tolerance of these effects may be mediated by the inhibition of the depolarization-dependent influx of calcium by these drugs.
209 citations
TL;DR: It is reported that prostacyclin inhibits the mobilisation of specific binding sites (‘receptors’) for fibrinogen on human platelets and that this effect parallels the inhibition of ADP- or thrombin-induced aggregation.
Abstract: Prostacyclin (prostaglandin I2, PGI2), produced by the blood vessel wall is the most potent known inhibitor of platelet aggregation induced by such stimuli as ADP and thrombin. It binds to a specific platelet receptor and activates adenylate cyclase, raising the cyclic AMP level in platelets. This property can be important because platelets participate in several significant interactions. For example, the interaction with fibrinogen or fibrin contributes to the formation of the haemostatic plug. Intact plasma fibrinogen is required for the aggregation of platelets induced by ADP, and endogenous platelet fibrinogen influences thrombin-induced aggregation. We have therefore studied the effect of prostacyclin on the interaction of fibrinogen with human platelets. We now report that prostacyclin inhibits the mobilisation of specific binding sites ('receptors') for fibrinogen on human platelets and that this effect parallels the inhibition of ADP- or thrombin-induced aggregation. The inhibitory effect of prostacyclin may limit the extent of platelet-fibrinogen interaction in vivo and in extracorporeal circulation.
184 citations
TL;DR: The purpose of the present report is to review some of the recent observations from this laboratory regarding C. d fJIcile and antibiotic-associated pseudomembranous colitis.
165 citations
TL;DR: Continuation of smoking during the treatment of small cell lung cancer was associated with a poor prognosis, while discontinuation ofsmoking, even at diagnosis, may have beneficial effects on survival.
Abstract: The prognostic implications of cigarette smoking were investigated in 112 patients with small cell lung cancer. Twenty had stopped smoking permanently before diagnosis (NS-Prior), 35 had stopped at diagnosis (NS-Dx), and 57 patients continued smoking (S). Therapies included chemotherapy alone or with radiation therapy, with or without thymosin fraction V. The survival difference among the three groups was statistically significant. The NS-Prior patients had the best survival, followed by NS-Dx patients and finally S patients. No S patient has survived, disease free, more than 96 weeks, while three NS-Prior and three NS-Dx patients are disease free 103 to 220 weeks after start of treatment. Thymosin, 60 mg/sq m, yielded survival benefits for the S group only. Continuation of smoking during the treatment of small cell lung cancer was associated with a poor prognosis, while discontinuation of smoking, even at diagnosis, may have beneficial effects on survival. ( JAMA 244:2175-2179, 1980)
149 citations
TL;DR: Three patients died after operation from intraabdominal sepsis as well as delayed arterial hemorrhage, suggesting earlier operative intervention may improve survival rates in this complex disease state.
149 citations
TL;DR: Localization of SLI to cells of the retina and characterizations of the molecular forms of retinal SLI suggest that the retina is a promising model system for studies on the potential neurotransmitter function of somatostatin.
Abstract: A substance with somatostatin-like immunoreactivity (SLI) was found in extracts of goldfish, frog, and cow retina. Dilutions of retinal SLI parallel the standard curve for radioimmunoassay obtained with synthetic somatostatin. Chromatography of goldfish retinal extract on Sephadex G-50 revealed two peaks of SLI, one that coeluted with synthetic somatostatin and one that eluted as a larger molecule. Incubation in 8 M urea did not alter the chromatographic pattern of the extract. SLI was present in extracts of frog optic nerve and tectum in concentrations higher than those found in the retina. In goldfish retina, SLI was localized by immunofluorescence to four types of processes in the inner plexiform layer; their origins could be traced to three classes of SLI-containing cell bodies in the proximal row of the inner nuclear layer and one class in the ganglion cell layer. Localization of SLI to cells of the retina and characterizations of the molecular forms of retinal SLI suggest that the retina is a promising model system for studies on the potential neurotransmitter function of somatostatin.
140 citations
TL;DR: Although the length of therapy is substantial (11 weeks), the program appears tolerable and is capable of inducing long‐term remissions and is currently being studied for dose escalation because neither local nor systemic side effects of a doselimiting nature have been observed at 20 mg/kg 5‐FU.
Abstract: Six patients with unresectable carcinoma of the esophagus received a combined course of external radiation therapy (1000 rads in four fractions in four days commencing on day 2) combined with constant infusional 5-fluorouracil (20 mg/kg every 24 hours for five days beginning on day 1). This program was repeated every other week to give a total x-ray dose of 6000 rads. This regimen has been well-tolerated by the majority of the patients and resulted in a complete response rate within the x-ray treatment field of 83% (5/6). All patients who showed a demonstrable systemic response to 5-fluorouracil reached complete response. The median survival has not yet been reached at six months with post-treatment survivors alive and without disease (four patients) at one, six, nine, and 22 months. Our previous median survival by x-ray therapy alone was 4 1/2 months. Toxicity consists primarily of hematologic suppression at a subclinical level. Although the length of therapy is substantial (11 weeks), the program appears tolerable and is capable of inducing long-term remissions. The program is currently being studied for dose escalation because neither local nor systemic side effects of a dose-limiting nature have been observed at 20 mg/kg 5-FU.
123 citations
TL;DR: It is concluded that regular cigarette smoking is associated with morphologic changes in the muscular pulmonary arteries that evolve in parallel with small airway disease and emphysema, and may be important in the eventual development of pulmonary hypertension and cor pulmonale.
Abstract: The muscular pulmonary arteries were studied by morphometric methods in 25 long-term cigarette smokers and were compared with those of 14 lifelong nonsmokers. Muscular pulmonary arteries < 500 microns in external diameter were identified and counted. The external diameter, medial thickness, and intimal thickness were measured in each of these arteries. Smokers had an increased number of transected muscular arteries < 200 microns in diameter (p < 0.03), increased medial smooth muscle (p < 0.02), and more intimal thickening (p < 0.04). Among smokers, these vascular changes correlated significantly with the severity of small airway disease and with the degree of emphysema, but not with bronchial mucous gland enlargement. We conclude that regular cigarette smoking is associated with morphologic changes in the muscular pulmonary arteries that evolve in parallel with small airway disease and emphysema. Although the functional significance of these findings is unknown, they may be important in the eventual development of pulmonary hypertension and cor pulmonale.
117 citations
TL;DR: Age-related changes in brain and pituitary beta-endorphin and ACTH must be considered in the evaluation of the physiological aging process and when comparing studies of these neuropeptides.
Abstract: Aging is associated with alterations in mood, thermoregulation, pain threshold, and stress response Because these functions may be modulated by endogenous opiates, we measured immunoreactive ACTH and
Journal Article•
TL;DR: Observations support the contention that this form of genetic obesity is characterized by elevated endogenous opiate levels and an increased sensitivity to opiate antagonists such as naltrexone or naloxone.
TL;DR: It is concluded that vitamin D metabolism by isolated cells is organ-specific, calvarial cells produce active metabolites of vitamin D in significant amounts, and locally produced, active metabolites could act locally, thereby adding a new dimension to the regulation of mineral metabolism by vitamin D metabolites.
Abstract: The question of whether the skeleton metabolizes 25-hydroxycholecalciferol [25(OH)D3] to more-polar products was studied. Calvarial cells were dispersed from 16-day old chicken embryos by using collagenase and then grown in culture in serum-free medium. Confluent cell cultures were incubated with 7 nM 25(OH)[3H]D3 for 2 hr, and the vitamin D metabolites were then extracted. At least four polar metabolites were produced. Based on separation by Sephadex LH-20 chromatography followed by high-pressure liquid chromatography, two of these metabolites were identified as 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25(OH)2D3]. These metabolites were also produced by cultured kidney cells but not by liver, heart muscle, or skin cells isolated from the same embryos. The specific activities of the calvarial 1- and 24-hydroxylases were similar in magnitude to those in isolated kidney cells. The specific activity of the calvarial 25(OH)D3:1-hydroxylase was inhibited by an 8-hr preincubation with 1,25(OH)2D3, whereas the 24-hydroxylase was enhanced. It is concluded that (i) vitamin D metabolism by isolated cells is organ-specific, (ii) calvarial cells produce active metabolites of vitamin D in significant amounts, (iii) vitamin D metabolism by calvarial cells is regulated by 1,25(OH)2D3, and (iv) locally produced, active metabolites could act locally, thereby adding a new dimension to the regulation of mineral metabolism by vitamin D metabolites.
TL;DR: In vitro susceptibility tests were performed on 84 strains of Clostridium difficile to 11 antimicrobial agents, showing that a major portion of the strains were relatively susceptible to the antimicrobial agent implicated in causing the disease.
Abstract: In vitro susceptibility tests were performed on 84 strains of Clostridium difficile to 11 antimicrobial agents. All isolates were from the stools of patients with antibiotic-associated diarrhea or colitis in which there was a cytopathic toxin that was neutralized by Clostridium sordellii antitoxin. Over 95% of the strains were susceptible to vancomycin, penicillin G, ampicillin, and metronidazole at concentrations of 4 microgram/ml. Susceptibility to clindamycin was variable; 60% of the strains were susceptible at 1 microgram/ml, and 9% were resistant at 128 microgram/ml. Studies of individual isolates showed that a major portion of the strains were relatively susceptible to the antimicrobial agent implicated in causing the disease.
TL;DR: Horace Fletcher, a popular 19th-century food faddist who advocated chewing food twice for each tooth, alluded to the possible dependence of absorption on thorough mechanical breakdown of food.
Abstract: Horace Fletcher, a popular 19th-century food faddist who advocated chewing food twice for each tooth, alluded to the possible dependence of absorption on thorough mechanical breakdown of food.1 How...
TL;DR: In this article, the possibilities for matching pets to owners' personality types for physical and psycho-social benefits were explored, and it was hypothesized that self-identified dog-and cat-lovers would show signi...
Abstract: The possibilities for matching pets to owners' personality-types for physical and psycho-social benefits were explored. It was hypothesized that self-identified dog- and cat-lovers would show signi...
TL;DR: The presence of a distinct size threshold (at 11·5 μm) implied that size alone may be a sufficient objective criterion for identification of human megakaryocytes.
Abstract: Human megakaryocytes have been isolated from marrow obtained from ribs removed at thoracotomy. All but one of the patients had normal pre-operative platelet and leucocyte counts. Megakaryocytes averaged 0.37% of all cells in marrow cell suspensions from nine consecutive subjects. A 283-fold purification (to 10.3%) was achieved by a density gradient centrifugation followed by two successive velocity sedimentations at unit gravity. The net yield, 12 800 megakaryocytes per specimen, was sufficient for many kinds of morphological study. Bright-field, phase contrast, and electron microscopy were used to characterize the younger and smaller megakaryocytes. Ploidy analyses were carried out on 100--235 megakaryocytes per specimen; 8N was the predominant ploidy class in isolated megakaryocyte populations from three individuals. The mean megakaryocyte diameter was 24 micrometers in three other specimens and the range was 10--48 micrometers. This data had a normal distribution and overlapped minimally with the size range of all other marrow cells. The presence of a distinct size threshold (at 11.5 micrometers) implied that size alone may be a sufficient objective criterion for identification of human megakaryocytes.
TL;DR: The recently isolated 28-residue sequence of prosom atostatin, a putative somatostatin precursor from pig hypothalamus and intestine, was synthesized by solid-phase methodology, characterized, and tested in rats for its effects on the release of insulin, glucagon, growth hormone, and prolactin.
Abstract: The recently isolated 28-residue sequence of prosomatostatin, a putative somatostatin precursor from pig hypothalamus and intestine, was synthesized by solid-phase methodology, characterized, and tested in rats for its effects on the release of insulin, glucagon, growth hormone, and prolactin. The synthetic product strongly suppressed plasma levels of insulin, glucagon, and growth hormone, and it appeared to be more active in the pancreas than in the pituitary. It inhibited insulin release about 5 times more effectively than somatostatin on a weight basis. The prohormone also suppressed growth hormone and prolactin levels in vitro. A time-course experiment for the effect of prosomatostatin on growth hormone release in vivo showed a significant suppression of plasma growth hormone for at least 90 min.
TL;DR: Empiric outpatient therapy with oral penicillin and/or dicloxacillin was effective and Gram stains made from wound swabs were specific but insensitive predictor for bacterial growth.
TL;DR: High salt intake accelerates hypertension in humans and increases cardiovascular morbidity and mortality and mortality in rats.
Abstract: High salt intake accelerates hypertension in humans and increases cardiovascular morbidity and mortality. The temporal relation between blood pressure (BP) elevation and appearance of vascular lesions during salt-loading was studied in the spontaneously hypertensive rat (SHR). Starting at 5 weeks of age, SHRs and normotensive Wistar-Kyoto rats (WKYs) were given 1% NaCl in their drinking water SHRs and WKYs on tap water served as controls. Animals from each group were sacrificed at 10 and 20 weeks of age, and the aorta and intrarenal vessels were studied by light and electron microscopy. Neither BP nor vascular morphology of WKYs were affected by 1% NaCl. In SHRs, the course of BP was not affected by the addition of salt for at least 11 weeks, but vascular changes were significantly aggravated within 5 weeks. Thus, aortic intimal lesions progressed more rapidly so that, by 20 weeks of age, 50% of the animals had 3+lesions while, in control SHRs, they did not exceed the 2+grade. Salt-loading resulted in significant thickening of the aortic media between the 10th and 20th week of age while control SHRs showed no increment within the same time interval. Also, small intrarenal arterial vessels of salt-treated SHRs had significantly narrower lumina and greater wall thickness at both 10 and 20 weeks of age. In addition, they showed intimal proliferations and necrotizing lesions which were absent from control SHRs at these ages. These results show that, in this experimental model, the aggravation of vascular changes is not merely a sequela of further elevation of BP. Since the adverse effect of salt on the vessels was not seen in WKYs, it is likely that this effect is related to genetic factors or to higher susceptibility of hypertensive vessels.
TL;DR: Two thousand six hundred ninety-three oral panoramic radiographs were reviewed, and thirteen patients displayed changes characteristic of lingual cortical defects of the mandible, which were almost equally distributed on the right and left sides.
TL;DR: The findings revealed that problem drinking was occurring in about half of these patients and described a variety of drinking-related effects that interfered with routine patient treatment and management.
TL;DR: It is proposed that glucagon acts to inhibit phosphofructokinase in the liver by decreasing the level of activation factor, and phosphorylation of the enzyme.
TL;DR: A prospective controlled clinical‐neurophysiological‐pathological study of 71 patients with oat cell carcinoma of the lung revealed no increased incidence of peripheral neuropathy at the initial stages of illness.
Abstract: A prospective controlled clinical-neurophysiological-pathological study of 71 patients with oat cell carcinoma of the lung revealed no increased incidence of peripheral neuropathy at the initial stages of illness. All patients developed neuropathy by the time they had lost 15% of their body weight, but the neuropathy was less severe than in 20 age-matched alcoholic patients with an equal degree of weight loss. The weight loss and peripheral neuropathy progressed with atrophy of type II (adenosine triphosphatase-positive) muscle fibers out of proportion to the patient's loss of body weight. By 40% body weight loss, all the patients had moderate symmetrical peripheral neuropathy, 6 had proximal brachial or lumbosacral plexus metastases, and 9 had distal pressure palsies. Mononeuritis multiplex developed in only 1 patient, who had diabetes mellitus. Two patients developed Eaton-Lambert syndrome, which resolved in 1 when chemotherapy controlled the systemic tumor, with no protein in the tumor postmortem which could produce the characteristic electromyographic findings of the syndrome.
TL;DR: A review of the clinical course of such tumors indicates that primary intraocular non-Hodgkin's lymphoma is usually a manifestation of a systemic neoplasm of the immune system.
Abstract: • Systemic and orbital reticulum cell sarcomas (RCSs) have been shown to be derived from lymphocytes, not reticulum cells or histiocytes, by immunologic and cytochemical characterization. Unfortunately, until now it has not been technically possible to study intraocular RCS. We have been able to immunologically characterize a primary intraocular RCS in a patient with chronic lymphocytic leukemia (ie, Richter's syndrome), establishing its origin from B lymphocytes. A review of the clinical course of such tumors indicates that primary intraocular non-Hodgkin's lymphoma is usually a manifestation of a systemic neoplasm of the immune system.
TL;DR: It is demonstrated that diamide induces a partially reversible erythrocyte lesion which is a useful model of oxidant-induced membrane injury, and it is suggested that oxidation plays an important role in the pathophysiology of chronic hemolysis which accompanies some G-6-PD variants.
Abstract: Erythrocytes from patients with chronic hemolytic variants of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency have structural membrane protein abnormalities accompanied by decreased cell membrane deformability which we postulate represent the consequences of oxidant-induced membrane injury To evaluate the pathophysiologic significance of oxidant-induced membrane injury, we studied the in vitro and in vivo effects of the thiol-oxidizing agent, diamide, on dog erythrocytes In vitro incubation of dog erythrocytes with 04 mM diamide in Tris-buffered saline for 90 min at 37 degrees C resulted in depletion of GSH, formation of membrane polypeptide aggregates (440,000 and > 50,000,000 daltons) and decreased cell micropipette deformability, abnormalities similar to those observed in the erythrocytes of patients with chronic hemolytic variants of G-6-PD deficiency In addition, diamide-incubated cells had increased viscosity and increased membrane specific gravity, but no change in ATP Reinjection of 51Cr-labeled, diamide-incubated cells was followed by markedly shortened in vivo survival and splenic sequestration Further incubation of diamide-incubated cells in 4 mM dithiothreitol reversed the membrane polypeptide aggregates, normalized micropipette deformability, decreased cell viscosity, prolonged in vivi survival, and decreased splenic sequestration These studied demonstrate that diamide induces a partially reversible erythrocyte lesion which is a useful model of oxidant-induced membrane injury They suggest that oxidant-induced erythrocyte membrane injury plays an important role in the pathophysiology of chronic hemolysis which accompanies some G-6-PD variants
Journal Article•
TL;DR: Preliminary evidence is provided that optimal nutritional support of the cancer patient may be possible without undesirable stimulation of tumor growth, and parenteral nutritional support in cancer patients does not maintain protein synthesis rates at levels greater than those present with regular oral diets.
TL;DR: It is demonstrated that the rabbit bladder can synthesize PGE2 and that the P GE2- synthesizing systems of the transitional epithelium and outer layer of bladder may be distinct.
Abstract: Synthesis of prostaglandin E2 (PGE2) by rabbit bladder was examined. PGE2 synthesis was assessed by thin-layer chromatographic analysis after conversion of [14C]-arachidonic acid to [14C]PGE2 or by a specific radioimmunoassay technique. Intact bladder and microsomes prepared from the bladder transitional epithelium (mucosal) layer and the outer vesicular layer demonstrated synthesis of PGE2. PGE2 synthesis was increased by arachidonic acid and blocked by indomethacin. When the inside medium (bathing the transitional epithelium) contained [14C]arachidonic acid, no detectable radioactivity was observed in the outside medium (bathing the outer layer). Conversely, when the outside medium contained [14C]arachidonic acid, no detectable radioactivity was observed in the inside medium. In addition, [14C]arachidonic acid was incorporated only into tissue directly exposed to bathing media containing the label. These results demonstrate that the rabbit bladder can synthesize PGE2 and that the PGE2- synthesizing systems of the transitional epithelium and outer layer of bladder may be distinct.
TL;DR: Balances of sodium, potassium, and water were studied in the growing male pig as hypertension developed in response to subcutaneous implantation of deoxycorticosterone acetate (DOCA) and Serum DOC levels rose dramatically on the day of the implant, then gradually declined but remained approximately 10 times greater than control levels 40 days after Implant.
Abstract: Balances of sodium, potassium, and water were studied in the growing male pig as hypertension developed in response to subcutaneous implantation of deoxycorticosterone acetate (DOCA). Serum sodium, potassium, deoxycorticosterone (DOC), aldosterone, and plasma renin activity (PRA) were determined. These variables were observed in a total of 10 experimental and nine control pigs. All animals were uninephrectomized and fed a diet of Purina Pig Chow and tap water ad libitum. No salt was added to the food or water. Serum DOC levels rose dramatically on the day of the implantation, then gradually declined but remained approximately 10 times greater than control levels 40 days after implant. Plasma renin activity was suppressed rapidly and completely, whereas aldosterone fell only slowly to about half its control value. Sodium retention was maximum during the first 24 hours. Therefore an "escape" process became operative, causing sodium balance to return to normal after the third day, at which time the major rise in arterial pressure occurred. A marked increase in water turnover (intake and output) also began after the third day and persisted throughout the experimental period. Water balance remained normal during this period of increased turnover. Hypokalemia developed in the absence of kaliuresis, suggesting that potassium moved into the cells. Except for the potassium retention, these changes parallel the abnormalities seen in other states of mineralocorticoid excess.