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Biomedical subjects

T R Morgan

Publications and source records attributed to T R Morgan.

At least 37 records · Page 2Linked to original sources

Atrial natriuretic peptide in portal vein-ligated rats: alterations in cardiac production, plasma level and glomerular receptor density and affinity.

The atrial natriuretic peptide hormonal system is altered to a variable degree in patients with cirrhosis. Portal pressure and portal-systemic shunting are also varied in cirrhosis. We used a portal vein-ligated rat model with predictable portal hypertension to study the effects of portal hypertension alone on the atrial natriuretic peptide hormonal system. Sham-operated rats were used as controls. Mean portal pressure was significantly increased in portal vein-ligated rats (portal vein-ligated rats, 21.7 +/- 0.74 cm H2O; sham-operated rats, 13.7 +/- 0.47 cm H2O; p less than 0.0001). Plasma atrial natriuretic peptide decreased 50% in the portal vein-ligated rats (p less than 0.0001). Atrial natriuretic peptide messenger RNA level was decreased by 40% to 60% in the left and right atria and in the ventricles of portal vein-ligated rats (p less than 0.05 for each chamber). Only one class of glomerular binding site was identified by competitive binding studies. The atrial natriuretic peptide glomerular receptor density increased in the portal vein-ligated rats (portal vein-ligated rats, 1,660 +/- 393; sham-operated 725 +/- 147 fmol/mg protein, p less than 0.02), whereas affinity decreased (portal vein-ligated, 1.69 +/- 0.49; sham-operated, 0.55 +/- 0.12 nmol/L, p less than 0.02). No difference was seen in the amount of cyclic GMP generated by atrial natriuretic peptide stimulation in isolated glomeruli from portal vein-ligated and sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased glomerular atrial natriuretic peptide receptor affinity in experimental nephrotic syndrome.

Atrial natriuretic peptide (ANP) is a cardiac hormone with natriuretic and diuretic effects. To better define the ANP hormonal system in the nephrotic syndrome, a condition associated with renal sodium retention, we undertook a study of glomerular ANP receptors in rats with puromycin aminonucleoside-induced nephrotic syndrome and in pair-fed controls. Nephrotic rats had significantly decreased serum albumin and total protein and significantly increased serum cholesterol, triglycerides and 24 hour urinary protein excretion. Plasma level of atrial natriuretic peptide was similar in both groups of rats. Competition binding inhibition studies in isolated glomeruli demonstrated one binding site in both groups of rats. The density of ANP binding sites in isolated glomeruli was similar in nephrotic and pair-fed rats while the binding affinity was increased significantly in the nephrotic rats. This is the first study to demonstrate alterations in renal ANP receptors in the nephrotic syndrome. Further studies will be necessary to determine whether alterations in glomerular ANP receptors contribute to renal sodium retention in the nephrotic syndrome.

Animals↗

Calcitonin gene-related peptide in hepatorenal syndrome. A possible mediator of peripheral vasodilation?

In advanced cirrhosis and hepatorenal syndrome, peripheral vasodilation is a prominent feature and may be pathophysiologically relevant. To determine whether the potent vasodilator, calcitonin gene-related peptide (CGRP), circulates at abnormal levels in patients with these disorders, we observed eight patients with alcoholic cirrhosis and hepatorenal syndrome, seven with alcoholic cirrhosis and ascites without hepatorenal syndrome, and 10 healthy controls. Plasma CGRP levels were higher in patients with alcoholic cirrhosis and hepatorenal syndrome (364 +/- 166 pg/ml) than in healthy controls (143 +/- 54 pg/ml, p less than 0.01). In patients with cirrhosis and ascites without hepatorenal syndrome, plasma CGRP levels were less elevated (291 +/- 257 pg/ml, NS). The identity of immunoreactive CGRP and synthetic hCGRP was confirmed by high performance liquid chromatography. These results suggest that CGRP may play a role in hepatorenal syndrome. However, to establish whether circulating CGRP contributes to the hemodynamic change in hepatorenal syndrome requires study of a larger number of patients and additional control groups.

Atrial Natriuretic Factor↗

Atrial natriuretic factor in experimental cirrhosis in rats.

Atrial natriuretic factor (ANF) is a cardiac hormone with potent natriuretic, diuretic, and vasorelaxant properties. Although abnormalities in ANF release, plasma level, and renal receptors have been described in humans and/or animals with cirrhosis and ascites, little is known about the ANF hormonal system in cirrhosis without ascites. The aim of this study was to examine the ANF hormonal system in an animal model of cirrhosis to determine whether compensated cirrhosis is associated with changes in the ANF hormonal system. Pair-fed rats were studied 5-7 weeks after either sham surgery or bile duct ligation. Bile duct-ligated (BDL) rats had elevated portal pressure and cirrhosis but did not have ascites. ANF messenger RNA levels were increased onefold in the atria of BDL rats. Sham-operated and BDL rats had similar plasma ANF levels. Competitive binding inhibition studies of isolated glomeruli showed a single class of receptors in sham-operated and BDL rats. The equilibrium dissociation constant was similar in sham-operated (0.51 nmol/L) and BDL (0.63 nmol/L) rats. Glomerular ANF receptor density increased significantly in BDL rats. Cyclic guanosine monophosphate generation in isolated glomeruli in response to 100 nmol/L ANF decreased slightly but not significantly in BDL rats. It was concluded that the ANF hormonal system is altered in cirrhosis without ascites; atrial messenger RNA level and glomerular ANF receptor density are increased.

Animals↗

Cytotoxicity of high energy shock waves: methodologic considerations.

In vivo and in vitro experimentation with high energy shock waves (HESW) is necessary to further our understanding of the biologic effects and potential application of this novel energy form. Factors are identified which are critical to the design and subsequent interpretation of HESW experimentation. First, the nature of the containment vessel and the presence or absence of acoustic interfaces are shown to significantly alter the outcome of cell suspension experiments. Second, the effects of HESW are shown to differ markedly for cells in suspension versus cells in tissue making comparisons between the two uncertain. Finally, the need for appropriate negative controls is demonstrated with in vivo experiments to control for the generalized toxicity which occurs when small animals are exposed to such an intense force distributed over a relatively large area. These findings affect the interpretation of previously reported work which investigated the cytotoxic potential of HESW.

Animals↗

Plasma human atrial natriuretic factor in cirrhosis and ascites with and without functional renal failure.

Functional renal failure of cirrhosis (FRFC) is a usually fatal syndrome of acute renal failure occurring in patients with advanced liver disease. Although not conclusively proven, most evidence suggests that renal arterial and arteriolar vasoconstriction is the cause of the renal failure in these patients. However, the mediators of the vasoconstriction remain unknown. Human atrial natriuretic factor (hANF) is a hormone with potent natriuretic, diuretic, and vasorelaxant properties. A deficiency of hANF could lead to renal arterial vasoconstriction and avid renal sodium retention as seen in FRFC. This study was undertaken to determine if patients with FRFC are deficient in circulating hANF. Seven patients with advanced alcoholic liver disease and renal failure of unknown cause (FRFC) were compared with 7 patients with advanced alcoholic liver disease, ascites, and normal serum creatinine as well as with 14 healthy volunteers. Plasma hANF was measured by radioimmunoassay. Plasma hANF was 742 +/- 227 pg/ml (mean +/- SEM) in patients with FRFC compared with 360 +/- 70 pg/ml in patients with liver disease and normal serum creatinine (p greater than 0.05) and 28 +/- 5.7 pg/ml in healthy volunteers (p less than 0.005 vs. FRFC and chronic liver disease, ascites, and normal serum creatinine). Thus, FRFC is not caused by a deficiency of circulating hANF. The elevated plasma hANF levels in patients with chronic liver disease and continued sodium retention may suggest a renal insensitivity to the natriuretic effects of hANF.

Adult↗

Free radical production by high energy shock waves--comparison with ionizing irradiation.

Fricke chemical dosimetry is used as an indirect measure of the free radical production of ionizing irradiation. We adapted the Fricke ferrous sulfate radiation dosimeter to examine the chemical effects of high energy shock waves. Significant free radical production was documented. The reaction was dose dependent, predictably increased by acoustic impedance, but curvilinear. A thousand shocks at 18 kilovolts induced the same free radical oxidation as 1100 rad cobalt-60 gamma ionizing irradiation, increasing to 2900 rad in the presence of an air-fluid zone of acoustic impedance. The biological effect of these free radicals was compared to that of cobalt-60 ionizing irradiation by measuring the affect on Chinese hamster cells by clonogenic assay. While cobalt-60 irradiation produced a marked decrease in clonogenic survivors, little effect was noted with high energy shock waves. This suggested that the chemical effects produced by shock waves were either absent or attenuated in the cells, or were inherently less toxic than those of ionizing irradiation.

Animals↗

False-positive secretin-KABI provocation test associated with achlorhydria.

Two patients with chronic abdominal pain and fasting hypergastrinemia had increases in serum gastrin of 440 and 300 pg/ml after injection of 2 U/kg Secretin-KABI. Both subsequently proved to have pentagastrin-fast achlorhydria. Intragastric instillation of 0.1 N HCl suppressed serum gastrin concentration by greater than 60%. In both, the pancreas was normal by sonography or computed tomography (CT) scan and at laparotomy in one. Both are currently asymptomatic 12 and 18 months later. We conclude that achlorhydria may be associated after injection of Secretin-KABI with a false-positive rise in fasting serum gastrin concentration of greater than 200 pg/ml and that gastric analysis for hypochlorhydria should be performed before secretin provocation testing.

Achlorhydria↗

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↗

HBsAg clearance in chronic active hepatitis B. A possible cause of cryptogenic cirrhosis.

Three patients with chronic hepatitis B infection, two with chronic active hepatitis and cirrhosis, and the third with quiescent cirrhosis, cleared HBsAg from their serum and eventually developed anti-HBs. All three were asymptomatic and had nearly normal serum aminotransferases following loss of HBsAg. Liver biopsy revealed cirrhosis in each patient. With the development of anti-HBs, these patients became serologically indistinguishable from patients with a cryptogenic cirrhosis who had prior unrelated exposure to hepatitis B. Remote chronic hepatitis B infection may be a more common cause of cryptogenic cirrhosis than is commonly appreciated.

Adult↗

Recurrent stomal variceal bleeding. Successful treatment using injection sclerotherapy.

Stomal varices may develop in patients with gastrointestinal stomas and portal hypertension. Bleeding often is recurrent and may be fetal. A 48-year-old woman had six major stomal variceal bleeds requiring 20 U of blood in the four months before beginning stomal sclerotherapy. "Paravariceal" injections using various combinations of sodium tetradecyl sulfate, ethanol, and saline resulted in a decrease in blood transfusions to 3 U during a 20-month follow-up. Injection sclerotherapy deserves consideration in patients with recurrent stomal variceal bleeding.

Female↗

Efficacy of radiologic studies in the detection of Barrett's esophagus.

Esophageal radiography using two different air-contrast techniques was used to examine 30 patients with Barrett's esophagus and 18 controls. All patients had upper gastrointestinal endoscopy and biopsy of the esophagus. The radiographs were randomized, masked, and then interpreted by two radiologists blinded to the endoscopic and biopsy diagnosis. Depending upon the diagnostic strategy of the radiologist, sensitivity varied from 0.36 to 0.83 and specificity from 0.56 to 1.00. A typical receiver-operating-characteristic curve was generated. Esophageal radiography is effective in identifying those patients who have stricture and ulceration as a complication beyond the epithelial transformation. However, because of low sensitivity, it is not a satisfactory method for identifying most cases of Barrett's esophagus.

Adult↗