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Biomedical subjects

D L Earnest

Publications and source records attributed to D L Earnest.

At least 55 records · Page 3Linked to original sources
PubMed1990

Controlling gastric pH: the impact of newer agents on the critically ill patient.

The critically ill patient is at increased risk for developing erosive injury of the stomach, duodenum, and esophagus. To date, the most effective way to prevent and treat this problem is by assuring excellent intensive care support and by reducing gastric acid secretion. The histamine H2-receptor antagonists (H2RAs) are effective in both prevention and treatment of such gastric mucosal injury. Newer agents are available that have potential for use in this setting, although none have been studied as extensively in critically ill patients as have the H2RAs. These new agents include proglumide, pirenzepine, misoprostol, omeprazole, and somatostatin. To date, only the latter has been extensively studied in critically ill patients. Omeprazole, which suppresses acid very effectively, may be problematic in the critically ill, limited by its oral dosage form, acid-labile properties, and potential drug interactions.

Alprostadil↗
PubMed1990

NSAID-induced gastric injury: its pathogenesis and management.

Injury to the gastric mucosa associated with the use of aspirin and other NSAIDs appears to be principally attributable to impairment of mucosal defense mechanisms against damage by acid and pepsin, that are mediated largely by prostaglandins. Modification of the drug dose or delivery system and substitution of a less gastrotoxic agent, such as a nonacetylated salicylate, are among the initial approaches that have been used to reduce the risk of NSAID-induced gastric injury. Other recommended measures include the avoidance of cigarettes, concentrated alcohol, and combination therapy with multiple NSAIDs. In high-risk patients, especially those with previous peptic ulcer disease, prophylactic therapy with a cytoprotective or acid-secretion-reducing drug is indicated. Drugs often used in the treatment of NSAID-associated mucosal damage include H2-receptor blockers, which inhibit gastric acid secretion, and agents such as synthetic prostaglandins and sucralfate, which improve mucosal defense. More potent inhibitors of gastric acid, such as drugs which block H+/K+ ATPase, may offer improved results for healing NSAID-induced gastric ulcers resistant to other therapy. Because NSAID-induced gastric lesions are not always accompanied by symptoms, patients receiving these drugs must be closely monitored for signs of gastric injury. Small ulcers can generally be healed with antiulcer medications. In patients with larger ulcers, withdrawal of NSAID therapy is usually required, at least until healing has occurred.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Pharmacokinetics and metabolism of retinol administered at a chemopreventive level to normal subjects.

Thirteen subjects between the ages of 50 years and 70 years were administered a daily 25,000 IU dose of retinol for 9 months. Two subjects experienced mild skin dryness, headaches, and/or alopecia. There were no significant changes in serum chemistries. High performance liquid chromatography assays for plasma retinol revealed no evidence of drug accumulation; however, there was a significant increase in the plasma concentration-versus-time curve for retinyl palmitate concentrations between the first and subsequent sampling days (P = 0.009). The mean skin retinol and retinyl palmitate concentrations in 7 retinol-treated subjects (131.7 and 15.9 ng/g, respectively) were not significantly different from those observed in 13 age-matched controls (118.9 and 25.5 ng/gm, respectively).

Adipose Tissue↗
PubMed1987

Synchronous neoplasms in patients with diminutive colorectal adenomas.

The distribution of synchronous neoplasms was retrospectively analyzed in 220 patients undergoing initial colonoscopic evaluation for colorectal neoplasms. In 159 of the 220 patients, an index neoplasm was present in the rectosigmoid region. Of these 159 patients, 32 had an index rectosigmoid adenoma less than 5 mm in diameter (diminutive), 105 had an index rectosigmoid adenoma greater than or equal to 5 mm in diameter and 22 had an index rectosigmoid adenocarcinoma. Among these patients with different index neoplasms the frequency of synchronous neoplasms was 34%, 53%, and 73%, respectively. The synchronous neoplasm was an adenoma greater than or equal to 5 mm in diameter in 13%, 40%, and 64%, respectively. The synchronous neoplasm was a carcinoma in 0%, 7%, and 5%, respectively. Two or more synchronous neoplasms occurred in 9%, 34%, and 41% of the index neoplasm groups, respectively. Finally, symptoms providing an indication for colonoscopy were present in 31%, 75%, and 86%, respectively. It is concluded that patients with diminutive index adenomas had fewer and smaller synchronous neoplasms (P less than 0.025) than patients with larger adenomas or invasive carcinoma as the index lesion. Thus, total colonoscopy does not appear to be necessary in asymptomatic patients with only diminutive adenomas found at flexible sigmoidoscopy.

Adenoma↗
PubMed1987

Effects of acute graft-vs-host disease on the liver of the brown Norway rat.

In this study we examined the effects of acute graft-vs-host disease (aGVHD) on the Brown Norway (BN) rat liver. When clinical signs of the disease appeared, rats were inoculated with fluorescent latex beads and 30 min later nonparenchymal cells were isolated from the liver. The cells were then analyzed via flow cytometry, histochemistry, and electron microscopy. Flow cytometry demonstrated that 58% of the cells from the 80 ml/min elutriation fraction (normally rich in Kupffer cells) of the non-GVHD liver had high fluorescence intensity compared to 8% in rats with aGVHD. Determination of the cellular composition of the various fractions with electron microscopy confirmed flow cytometry observations in that only 9% of the 80 ml/min elutriation fraction of GVHD livers had peroxidase-positive rough ER and the morphological appearance of macrophages as compared to 60% in the non-GVHD liver. The low percentage of fluorescent-positive Kupffer cells in the 80 ml/min elutriation fraction of the GVHD liver is attributed to a massive lymphocytic invasion of the liver and not necessarily to a defect in the mononuclear phagocyte system.

Acute Disease↗
PubMed1987

Endotoxin-induced liver injury in aged and subacutely hypervitaminotic A rats.

The plasma disappearance of endotoxin and endotoxin-induced hepatic injury were studied in two rat models: the aging rat and the subacutely hypervitaminotic A rat. The choice of these models was based on their respective association with a decreased or increased Kupffer cell endocytic activity. The half-life of endotoxin (E. coli O26: B6, phenol extracted) in plasma was significantly prolonged in aged rats as measured by both the Limulus assay (t1/2 = 2.1 +/- 0.1 h in 3-6-month-old, and 3.3 +/- 0.3 h in 24-36-month-old rats) and 51Cr-labeled endotoxin radioactivity assay (t1/2 = 5.3 +/- 0.3 h in 3-6-month old and 7.7 +/- 0.6 h in 24 36-month-old rats). In subacute hypervitaminosis A, the half-life of endotoxin was significantly decreased in the Limulus assay (t1/2 = 2.1 +/- 0.1 h in 3-6-month old and 1.4 +/- 0.2 h in subacutely hypervitaminotic A rats), but not in the radioactivity assay (t1/2 = 5.3 +/- 0.3 h in 3-6-month-old and 5.0 +/- 0.4 h in subacutely hypervitaminotic A rats). Hundred percent mortality was observed at a dose of 2 mg endotoxin/100 g body wt. in old rats, but not in young rats. Only 1 of 7 young subacutely hypervitaminotic A rats died following injection of this dose of endotoxin. The dose of endotoxin which caused only minimal parenchymal liver cell injury in young rats induced substantial parenchymal cell injury in old rats and subacutely hypervitaminotic A rats as determined by both histological and biochemical parameters. It is concluded that some basic characteristics of experimental animals, such as age and nutritional status, can dramatically influence the sensitivity to endotoxin and this is not necessarily correlated with the rate of endotoxin clearance.

Aging↗
PubMed1985

Hepatobiliary scintigraphy for cholestasis in congenital hepatic fibrosis. Diagnosis and treatment.

A 9-year-old child with congenital hepatic fibrosis had dilated intrahepatic bile ducts and recurrent cholangitis. Choleretic agents were administered to prevent recurrent cholangitis. Response to treatment was monitored with serum bile acid concentrations and computer-assisted technetium Tc 99m iprofenin (Pipida) scintigraphy. Dehydrocholic acid with meals improved hepatobiliary excretion of the radioactive isotope and lowered serum bile acid levels but did not prevent cholangitic attacks when used alone. Sulfamethoxazole and trimethoprim used alone prevented infection, but a steady rise in serum bile acid concentrations suggested increasing cholestasis. During combined drug treatment, the patient remained free of cholangitis for at least two years. Optimal therapy of congenital hepatic fibrosis with cholestasis but without mechanical biliary obstruction may involve the combined use of a choleretic such as dehydrocholic acid plus a suppressive antibiotic.

Bile Ducts, Intrahepatic↗
PubMed1985

The yield of diagnostic upper endoscopy: results of a prospective audit.

Because of its widespread availability and the generally increasing economic pressure, endoscopy needs critical scrutiny to establish appropriate clinical guidelines. We carried out a prospective evaluation of 200 consecutive upper gastrointestinal (GI) endoscopies to ascertain the frequency of abnormal findings when specific indications were the impetus to endoscopy. Those indications were esophageal complaints, upper GI bleeding, abdominal discomfort, known premalignant disorders and abnormal findings on barium meal. The overall frequency of abnormal findings for all indications was 66%. Abnormal endoscopic findings were most often present when upper GI bleeding or premalignant conditions (88 and 87%, respectively) were reasons for endoscopy. Endoscopic confirmation of lesions seen on barium meal was 64%. Only 37% of patients endoscoped for abdominal discomfort had abnormal findings. Moreover, as symptoms resolved in 70% of such patients within 1 to 9 weeks, the low yield of endoscopy suggests that our current threshold for endoscopy in this setting may be too low. Refinement of the indications for and reassessment of the timing of endoscopy are needed.

Abdomen↗
PubMed1984

Oxalate and chloride absorption by the rabbit colon: sensitivity to metabolic and anion transport inhibitors.

The effects of transport inhibitors on the movements of oxalate and chloride across the isolated short circuited rabbit colon were studied. Net oxalate absorption was shown in this species and was shown to be an energy dependent process as indicated by its sensitivity to 2-4 dinitrophenol (DNP) 10(-4)M. Mucosal addition of 4-acetamido-4-isothiocyano-2,-stilbene-2,2'-disulfonic acid (SITS) 10(-4)M abolished the net flux of both oxalate and chloride. Acetazolamide (8 mM) in bicarbonate free buffer significantly reduced the mucosal to serosal flux of both anions. These results suggest that in rabbit colon, oxalate and chloride share a common transport pathway and implicate the chloride bicarbonate exchange system. This study also confirms that chloride absorption by the short circuited rabbit colon is an electrically silent process and presents evidence that suggests that chloride absorption is mediated by a chloride bicarbonate exchange system located in the apical membrane of absorbing colonic epithelial cells.

2,4-Dinitrophenol↗
PubMed1983

Vanadium ion stimulation of chloride secretion by rabbit colonic epithelium.

Ionized forms of vanadium are known to exert diverse biological activities. Of particular interest in the inhibitory action of the vanadium ion on (Na+ + K+)-ATPase. This report describes another action of the vanadium ion on the rabbit colonic epithelium. Micromolar quantities of vanadate, applied to the serosal side of the isolated rabbit colonic epithelium, result in a stimulation of electrogenic chloride secretion by this epithelium. Sodium transport is unaffected by the vanadium ion in the concentrations used in this study. It is proposed that the vanadyl ion activates adenylate cyclase and thereby initiates subsequent secretory events.

Animals↗
PubMed1983

The effect of intestinal esterase inhibition on the in vivo absorption and toxicity of Di-n-butyl phthalate.

Inhibition of intestinal mucosal esterases by S,S,S-tributylphosphorotrithioate (DEF) did not alter the gastro-intestinal absorption of di-n-butyl phthalate (DBP) in the rat. After intragastric administration of [14C]DBP to control and esterase-inhibited animals, the disappearance of 14C from the small intestine and the levels of 14C in the blood were not significantly different in the two groups over the first 4 hr. Peak blood levels of 14C occurred 2 hr after dosing in both groups of rats. The circulating [14C]butyl phthalate in the diester form accounted for less than 5% of the total 14C at 2 hr, regardless of intestinal esterase activity. The remaining 14C was associated with mono-n-butyl phthalate or more polar metabolites. These data suggest an important role for pancreatic esterases, which may be protected from DEF-mediated inhibition by storage in zymogen granules, in the metabolism and absorption of DBP.

Animals↗
PubMed1983

Dihydroxy bile salt-induced alterations in NaCl transport across the rabbit colon.

The effects of increasing mucosal or serosal concentrations (1-4 mM) of taurochenodeoxycholate (TCDC) on sodium chloride transport across the isolated, short-circuited rabbit colon were examined. Mucosal TCDC produced dose-related increases in tissue conductance (Gt) and the unidirectional fluxes of Na+ and Cl- and dose-related decreases in net NaCl absorption. At 4 mM mucosal TCDC, Gt was increased fivefold, net sodium flux (JNanet) was reduced 50%, and JClnet was abolished. Serosal TCDC also produced dose-dependent changes in permeability that were quantitatively different. Four millimolar serosal TCDC produced a 2.7-fold increase in Gt, abolished JNanet, and stimulated electrogenic Cl- secretion. TCDC-induced Cl- secretion was stimulated by 10(-5) M serosal TCDC, inhibited by serosal furosemide or ouabain, did not alter theophylline-induced secretion (and vice versa), and occurred in the absence of serosal Ca2+. It is suggested that 1) TCDC inhibition of sodium absorption is indirect (i.e., not simply due to a reduction in the activity of the Na "pump," since Cl- secretion persists during conditions that abolish JNanet) and 2) TCDC induces Cl- secretion by enhancing the activity of basolateral membrane adenylate cyclase.

Animals↗
PubMed1983

Role of tight-junctional pathways in bile salt-induced increases in colonic permeability.

The effects of a dihydroxy bile salt, taurochenodeoxycholate (TCDC), on the permeability and conductance of isolated, short-circuited segments of the rabbit descending colon were examined using conventional Ussing chamber techniques. Increasing concentrations of TCDC (1-4 mM) produced dose-dependent increases in sodium backflux (JNas leads to m) and tissue conductance (Gt) when applied to either the mucosal or serosal salines. However, mucosal addition was twice as potent in increasing JNas leads to m and Gt at 4 mM. Tracer experiments indicated that the transepithelial serosal-to-mucosal fluxes of sodium and mannitol are via an aqueous, unrestricted, free-solution pathway, while albumin movements are restricted through this pathway both in the absence and presence of mucosal TCDC. The changes in JNas leads to m, JMans leads to m, and Gt caused by 4 mM mucosal TCDC were largely reversed by rinsing the mucosal chamber with fresh buffer. It was also observed that osmotically induced volume flows in the serosal-to-mucosal direction could offset or reverse the changes in Gt produced by 2 mM mucosal TCDC, suggesting that the enhanced conductance pathway is in series with the lateral intercellular spaces. Taken together, these results suggest that low concentrations of TCDC alter the integrity of tight-junctional complexes between the epithelial cells of the rabbit colon.

Animals↗
PubMed1983

"Pseudo-ascites" associated with giant ovarian cysts and elevated cystic fluid amylase.

Two patients with massive ovarian cysts that mimicked ascites on physical examination, ultrasonography, and abdominal plain film are reported. Elevated cyst amylase in both patients, and in one, elevated serum amylase, further confused the diagnosis. Massive ovarian cysts should be considered in the differential diagnosis of presumed ascites in female patients, particularly in the setting of elevated serum or "ascitic" fluid amylase.

Adult↗
PubMed1982

Prothrombin antigen and coagulant activity in patients with liver disease.

Plasma levels of prothrombin immunoreactive protein (factor II antigen) (II-Ag) and coagulant activity (II-CA) were determined in eight patients with acute hepatitis and in 29 patients with chronic liver disease (cirrhosis). The II-CA was reduced in 23 (62%), II-Ag in 17 (46%), and both were reduced in 13 (36%) of the cases. A disproportionate reduction was noted in 21 (57%); ie, there was more II-Ag found in comparison to the corresponding level of II-Ca. Ninety-six percent (23) of 24 patients with moderate to severe hepatocellular disease showed reduced II-CA levels; 63% (15) showed reduced II-Ag levels, with a disproportionate reduction in II-CA in 67% (16). These data suggest that reduced synthesis as well as impaired carboxylation of prothrombin precursor protein are factors contributing to the coagulopathy in patients with moderate to severe liver disease and that measurement of circulating levels of II-Ag may provide an excellent indication of hepatic synthetic capacity.

Adolescent↗