A simplified technique for constructing a feeding jejunostomy from an existing gastrostomy.
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Biomedical subjects
Publications and source records attributed to B R Bacon.
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Peroxidative injury to the mitochondrial inner membrane with resultant defects in oxidative metabolism may be partially responsible for hepatocellular injury in iron overload. We examined the effects of iron-induced lipid peroxidation in vitro on hepatic mitochondrial morphology and function and determined if various inhibitors of free-radical-mediated injury could be protective. Normal rat liver mitochondria were prepared by differential centrifugation and were incubated with 1, 2, and 3 microM Fe2+, NADPH, and with and without oxygen radical scavengers, iron chelators, and antioxidants. There was a direct linear relationship between the concentration of added iron and the degree of lipid peroxidation as measured by malondialdehyde (MDA) production (r = .85). With 3 microM Fe2+ there was a decrease in the respiratory control ratio (RCR) for all four substrates tested; this decrease in RCR was due to a decrease in the state 3 respiratory rate for all substrates, with no changes in the state 4 respiratory rate for glutamate, beta-hydroxybutyrate, or succinate. Oxygen radical scavengers failed to prevent iron-induced lipid peroxidation or to protect against associated mitochondrial dysfunction. Iron chelators and antioxidants prevented MDA formation and mitochondrial function was maintained. Iron-induced lipid peroxidation in vitro produces an irreversible inhibitory defect in mitochondrial electron transport that may be specific at complex IV (cytochrome oxidase).
We determined quantitatively the amount of sodium morrhuate that reaches the pulmonary vascular bed during endoscopic variceal sclerotherapy to ascertain whether this affects the diffusing capacity of the lung to carbon monoxide (DLCO). Eleven patients had measurements of DLCO and specific diffusing capacity (DLCO/VA) before and after sclerotherapy. In ten of these patients sclerotherapy was done using sodium morrhuate mixed with 99mTc-labeled albumin microspheres followed by quantitative radionuclide scanning. Most of the sodium morrhuate, 80 +/- 18% (SD) of the total dose, remained in the region of the esophagus. Only 20% of the injected dose reached the pulmonary circulation. There were no changes in DLCO or DLCO/VA. We conclude that most of the sclerosing solution injected during endoscopic variceal sclerotherapy remains at the site of injection. As a result, the pulmonary endothelium is exposed to small amounts of sodium morrhuate and no change in diffusing capacity occurs.
A rapid, sensitive analytical procedure was developed to quantitate alpha-tocopherol in rat liver. Liver is homogenized in acetone, fractionated by reversed-phase high-performance liquid chromatography and alpha-tocopherol quantitated by monitoring the column effluent at 280 nm. A single analysis requires 18 min. The method is linear from 1.0 to greater than 30.0 micrograms alpha-tocopherol per g of liver (wet weight). The average relative standard deviation of the slope of the standard curve is 2.3% and the single-day coefficient of variation is 6.3%. The use of an acetone extraction, reversed-phase column chromatography and quantitation of alpha-tocopherol at 280 nm results in a sensitive and reproducible system for the determination of alpha-tocopherol concentrations in rat liver. Preliminary studies have shown the assay to be useful for investigation of the effects of age and diet on hepatic alpha-tocopherol concentration.
The prevalence of pleural effusions after endoscopic variceal sclerotherapy was reviewed in 30 patients undergoing 65 sclerotherapy sessions. Pleural effusions were identified radiographically after 31 of the 65 (48%) sclerotherapy sessions. Eleven of the effusions were right-sided, 10 were left-sided, and 10 were bilateral. Most of the effusions (20 of 31, 65%) were small. Significant postsclerotherapy chest pain was found more commonly in those patients who developed pleural effusions (11 of 31, 35%) compared with those who did not (4 of 34, 12%) (p less than 0.05). The total sclerosant volume injected was significantly greater in those who developed effusions (13.2 +/- 5.8 ml) (mean +/- SD) than in those who did not (8.5 +/- 4.5 ml) (p less than 0.001). Twelve effusions were analyzed biochemically after thoracentesis. Eleven effusions met one or more of three criteria commonly used to identify exudative effusions. We conclude that pleural effusions develop frequently after sclerotherapy. The effusions are predominantly exudative in character and presumably arise from inflammation of the mediastinal parietal pleura.
Adult respiratory distress syndrome has been reported after endoscopic variceal sclerotherapy with sodium morrhuate. It has been proposed that sclerosant entering the pulmonary circulation during intravariceal injections may cause pulmonary hypertension and capillary injury. The purpose of this study was to determine whether variceal sclerotherapy with sodium morrhuate causes capillary injury or pulmonary edema in humans. We studied the effect of sclerotherapy on gas exchange and pulmonary and systemic hemodynamics in 8 patients who required endoscopic variceal sclerotherapy for treatment of variceal hemorrhage. The pulmonary vascular resistance index increased from 246 +/- 67 dyn X s X cm-5/m2 (mean +/- SEM) at baseline to a high of 303 +/- 85 dyn X s X cm-5/m2 60 min after sclerotherapy (normal range 250-500 dyn X s X cm-5/m2). Pulmonary artery pressure remained stable while cardiac index decreased by 12% over the same period. There were also small increases in systemic vascular resistance index and systemic arterial pressure after sclerotherapy. Although there was no change in arterial oxygen tension, the alveolar-arterial oxygen difference improved after sclerotherapy. These results indicate that variceal sclerotherapy with sodium morrhuate is associated with clinically insignificant changes in pulmonary and systemic hemodynamics. We did not detect evidence of acute lung injury after sclerotherapy.
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Experimental animals that had been given excess iron in their diet were studied by magnetic resonance (MR) imaging in vivo and by magnetic resonance (MR) spectroscopy in vitro. Hepatic iron overload in patients with transfusional iron excess was studied by MR imaging, and isolated iron protein fractions were studied in vitro by MR spectroscopy. The spin echo image intensity of livers with iron overload was decreased because of the extreme decreases in T2 compared with normal; T1 was decreased only moderately. The relaxation rates 1/T2 and 1/T1 both showed a linear relationship to hepatic iron levels. Ferritin solutions showed moderate decreases in T2 and mild decreases in T1. The T2 relaxivity of ferritin, which is due to the iron core rather than the apoferritin protein shell, does not appear sufficient to account for the extreme decrease in T2 observed in hepatic iron overload. Low molecular weight cytosol iron is present in lower concentrations than ferritin but potentially has much greater relaxivity and may contribute to the MR findings. These techniques may be useful in other studies of iron metabolism.
The role of dietary sucrose concentrations in the development of hepatic steatosis in rats was investigated. Twelve groups of weanling male Sprague-Dawley rats received semipurified diets with different sucrose concentrations ranging from 20 to 50% (w/w); one group received a cereal-based chow diet. Rats were sacrificed after 3 weeks and body weight, liver/body weight ratio, plasma alanine aminotransferase concentration, hepatic triglyceride concentration, and liver morphology (light and electron microscopy) were determined. Body weight and liver/body weight ratio were decreased in rats receiving 40-50 or 25-35% dietary sucrose compared to rats receiving 20% sucrose or chow. Plasma alanine aminotransferase concentrations were within normal limits. Hepatic triglyceride concentration was significantly increased in rats receiving 40-50 and 25-35% dietary sucrose compared to rats receiving 20% dietary sucrose or chow. Light microscopy showed hepatic steatosis in a periportal distribution at all concentrations of dietary sucrose. Both the frequency and the severity of the steatosis were increased with increasing dietary sucrose concentrations. Electron microscopy from selected livers with increased hepatic triglyceride concentrations revealed increased lipid spheres and increased smooth endoplasmic reticulum without prominent Golgi apparatus or GERL complex. It is concluded that high dietary sucrose concentrations are responsible for the development of hepatic steatosis. Semipurified diets with high dietary sucrose concentrations such as the AIN-76A diet (50% sucrose) should not be used in animal studies in which increased triglyceride deposition could influence experimental outcome.
An integrated approach to normal hepatic iron metabolism requires an understanding of the complex interactions between the dynamic processes of iron uptake, utilization, storage, and release. Lack of knowledge of the specific chemical and physical properties of certain critical compartments of hepatic iron (such as the transit pool and hemosiderin) and of their relative turnover rates has made it extremely difficult to assign precise parameters to their dynamic interactions. With refinement in biochemical and biophysical techniques and with their application to valid biologic models, it should be possible to obtain insights into these areas, which are currently obscure.
A 1-h basal collection of gastric secretions was taken from 14 healthy full-term infants (group I) and 10 premature infants (group II). Simultaneously, acid and intrinsic factor (IF) secretion was measured. In an additional group of 19 full-term infants (group III), 16 had IF detectable in their gastric secretions immediately at birth. Volumes of gastric juice (ml/kg/h) and IF secretion (ng/kg/h) were similar for group I and group II infants. Acid secretion (mEq/kg/h) was significantly less in group II (p less than 0.01). There was a linear correlation between acid secretion (mEq/kg/h) and IF secretion (ng/kg/h) for group I (r = 0.85, p less than 0.001). There was no correlation between the values for the premature infants in group II. The study documents that the parietal cell of the premature infant has the same capacity to secrete IF as the cell of the more mature infant. It also demonstrates the presence at birth of IF in gastric secretions, which suggests in utero secretion and independence from enteral feeding for stimulation.
The incidence of clinically apparent retinal changes in 35 anemic patients and 35 age- and sex-matched control subjects was studied. Retinal photographs of all subjects were obtained. From these, all vascular and extravascular retinal lesions were noted. No retinal abnormalities were observed in the control subjects. Seven (20%) of the anemic patients exhibited extravascular lesions. There was no relationship detected between the occurrence of these changes and the severity or the cause of the anemia. Employing the assumption that true venous length for a given net distance traveled correlates with the degree of venous tortuosity, venous length over a standard radial distance from the optic disc was assessed with a curvometer. A significant negative correlation was determined between venous length and the level of hematocrit, thereby implying that retinal venous tortuosity is directly related to severity of anemia.
Experimental animal models of hepatitis, fatty liver, and hepatic iron overload were evaluated using a 3.5-kGauss nuclear magnetic resonance (NMR) imaging system. Increases in image intensity measurements and in T2 relaxation times equalled the sensitivity of histologic findings for the detection of early stages of hepatitis. A significant shift in T1 relaxation times characterized the early stages of hepatic necrosis. Liver triglyceride content correlated significantly with increases in NMR intensity measurements (p less than 0.01); however, changes in liver water content had a much greater influence on intensity, T1, and T2. Thus, it may be possible to distinguish hepatitis from benign fatty liver. Liver iron content correlated with decreases in NMR intensity measurements (p less than 0.001), and iron levels as low as 1.2 mg/g were detected. NMR may more specifically identify hepatocellular iron overload than do other techniques that do not distinguish hepatocellular from reticuloendothelial iron.
Peroxidative decomposition of cellular membrane lipids is a postulated mechanism of hepatocellular injury in parenchymal iron overload. In the present study, we looked for direct evidence of lipid peroxidation in vivo (as measured by lipid-conjugated diene formation in hepatic organelle membranes) from rats with experimental chronic iron overload. Both parenteral ferric nitrilotriacetate (FeNTA) administration and dietary supplementation with carbonyl iron were used to produce chronic iron overload. Biochemical and histologic evaluation of liver tissue confirmed moderate increases in hepatic storage iron. FeNTA administration produced excessive iron deposition throughout the hepatic lobule in both hepatocytes and Kupffer cells, whereas dietary carbonyl iron supplementation produced greater hepatic iron overload in a periportal distribution with iron deposition predominantly in hepatocytes. Evidence for mitochondrial lipid peroxidation in vivo was demonstrated at all three mean hepatic iron concentrations studied (1,197, 3,231, and 4,216 micrograms Fe/g) in both models of experimental chronic iron overload. In contrast, increased conjugated diene formation was detected in microsomal lipids only at the higher liver iron concentration (4,161 micrograms Fe/g) achieved by dietary carbonyl iron supplementation. When iron as either FeNTA or ferritin was added in vitro to normal liver homogenates before lipid extraction, no conjugated diene formation was observed. We conclude that the presence of conjugated dienes in the subcellular fractions of rat liver provide direct evidence of iron-induced hepatic mitochondrial and microsomal lipid peroxidation in vivo in two models of experimental chronic iron overload.
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Two patients became severely pancytopenic while receiving azathioprine in low dosages for treatment of connective-tissue diseases. While mild hematologic complications are common with this drug, we believe that the degree of bone marrow suppression exhibited in these two patients is unusual, especially at the dosages (0.75 and 1.25 mg/kg/day) of azathioprine being used.
We present here results of studies on four patients (three men, one woman) who had had cadaver renal transplants and in whom renal artery stenosis and hypertension developed. Erythropoietin-dependent erythrocytosis developed in association with these changes in the three men. All patients had stable renal function and the hypertension was well controlled. Absolute erythrocytosis thought to be secondary to local renal hypoxia due to decreased renal blood flow developed in two of the men. Erythrocytosis developed in the other man but his RBC mass was at the upper limit of normal. In these patients, we suspect that the erythropoietin-dependent erythrocytosis is secondary to intrarenal hypoxia due to renal artery stenosis. Erythrocytosis or elevated erythropoietin levels failed to develop in the woman despite severe renal artery stenosis. Possible reasons for this discrepancy are discussed.
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