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Biomedical subjects

S J Saunders

Publications and source records attributed to S J Saunders.

At least 37 records · Page 2Linked to original sources

A prospective evaluation of injection sclerotherapy in the treatment of acute bleeding from esophageal varices.

In a 25 month study of massive upper-gastrointestinal hemorrhage, 64 patients were shown to have esophageal varices on emergency endoscopy. Twenty-four patients were actively bleeding from varices and were treated with a Sengstaken tube, and in 22 this was followed by emergency injection sclerotherapy using a rigid esophagoscope and general anesthesia. These 22 patients were followed prospectively and had 51 episodes of endoscopically proven active bleeding from esophageal varices which required Sengstaken tube control of hemorrhage during 36 separate admissions. This group included our total experience of injection sclerotherapy in acute variceal bleeding. The majority (14 of 22 patients) had alcoholic cirrhosis. Definitive control of variceal bleeding during the period of hospitalization was achieved in 33 hospital admissions (92%), usually with a single injection (27 hospital admissions: 75%). The results were satisfactory in 26 hospital admissions (72%). There were nine deaths (41% overall patient mortality rate), but no patient died primarily of variceal bleeding, and exsanguinating variceal bleeding was no longer a problem. The mortality rate per injection was 18%, and the mortality rate per hospital admission was 25%. Injection sclerotherapy is proposed as the emergency treatment of choice for patients with proven bleeding esophageal varices who do not stop bleeding on initial conservative treatment.

Acute Disease↗

A prospective controlled trial of sclerotherapy in the long term management of patients after esophageal variceal bleeding.

The preliminary results of the first 25 months of a prospective randomized controlled clinical trial, designed to compare repeated injection sclerotherapy with conservative medical management in the long term treatment of all patients shown to have previously bled from esophageal varices, are presented in detail. To date, 31 patients have been randomized, 15 in the chronic injection group and 16 in the control medical management group. In addition, five patients excluded for geographic reasons have been injected out of trial. Ethanolamine oleate has been injected into the varices, using a modified rigid esophagoscope under general anesthesia. The preliminary results have been encouraging. It has been possible to eradicate esophageal varices in the chronic injection group and, once the varices had been eradicated, no patient had recurrence of variceal bleeding. On the other hand, recurrent variceal bleeds have remained a continuing problem in a number of the patients in the control study. A longer follow-up period will be required to assess both the quantitative and the qualitative aspects of survival and to determine how long esophageal varices will remain eradicated as well as how frequently repeated injections will be required.

Adolescent↗

alpha-Fetoprotein in liver disease.

Ther serum concentration of alpha-fetoprotein (AFP) was measured by radio-immunoassay in 98 patients with liver disease including hepatoma, chronic active hepatitis, alcoholic cirrhosis, and acute virus B hepatitis. Raised AFP levels, above 30 ng/ml, were found in 87% of patients with acute viral hepatitis, in 82% of patients with primary liver cell carcinoma, in 58% with chronic active hepatitis and in 14% of patients with alcoholic cirrhosis. However, levels above 1 000 ng/ml were found only in patients with hepatoma and in acute viral hepatitis.

Adolescent↗

Serum factor affecting neutrophil function during acute viral hepatitis.

Sera from eight of 17 patients with acute viral hepatitis was deficient in its ability to support neutrophil bactericidal function in vitro. This defect appeared to be related to the viral infection itself. Sera from patients with drug hepatitis or mechanical obstructive jaundice did not show this effect.

Acute Disease↗

Radioimmunoassay of plasma ligandin: a sensitive index of experimental hepatocellular necrosis.

The development of sensitive and specific radioimmunoassay for ligandin, a protein present in abundance in the hepatic cytoplasm, has permitted measurement of ligandin in rat plasma. Plasma ligandin levels were estimated in normal, carbon tetrachloride (CCl4)-treated, and bile duct-ligated rats, with parallel estimation of serum glutamic oxaloacetic transaminase (SGOT). Plasma ligandin levels rose at a greater rate and to higher levels than did SGOT in CCl4-treated rats and showed a more linear increment to increasing doses of CCl4. A marked depletion of hepatic, but not renal ligandin, was associated with CCl4 poisoning. Twelve hours after acute bile duct ligation, both plasma ligandin and SGOT were moderately elevated, plasma ligandin returning to normal by 24 hr, at which time SGOT was still raised. The findings of this study indicate that plasma ligandin is a sensitive index of experimental hepatocellular necrosis.

Animals↗

Ligandin heterogeneity : evidence that the two non-identical subunits are the monomers of two distinct proteins.

Purified ligandin (Y-protein) a 46000-dalton protein, has been shown to consist of two subunit species (mol. wts. 22 000 and 24 000) on discontinuous polyacrylamide gel electrophoresis in sodium dodecyl sulphate. This technique was used to define further the nature of these subunits. The Y sulphobromophthalein-binding fraction of rat hepatic cytosol was shown to contain three major subunit bands designated subunit Ya, subunit Yb and subunit Yc in ascending order of size. Purified ligandin was found to comprise Ya and Yc subunit species, and also gave two bands on isoelectric focusing. The two subunit species in purified ligandin were partially separated by an additional purification step. Antiserum to ligandin reacted mono-specifically with the purified protein, as well as hepatic, renal and small intestinal mucosa cytosol, but gave lines of identity and partial identity with cytosol from testis, ovary and adrenal gland. The Y fraction of testis was found to contain only Yb and Yc species, while all three major bands were found in liver, kidney and small intestinal mucosa. Phenobarbital treatment increased the concentration of Ya and Yb in the liver, but had little effect on Yc. These findings suggest that the Ya and Yc ligandin subunits are the monomers of two proteins: YaYa and YcYc.

Animals↗

Experimental liver necrosis: hepatic erythrocyte sequestration as a cause of acute anemia.

A prospective study was undertaken to determine the cause of the acute anemia previously observed in pigs manifesting acute liver necrosis after administration of acetaminophen in dosages in excess of the LD100. A highly significant correlation was found between the degree of anemia and increase in liver weight (P less than 0.001) and a similarly significant correlation was noted between the increase in liver weight and 51Cr activity in the liver after administration of autologous erythrocytes labeled with 51Cr. Marked hepatic erythrocyte sequestration was confirmed histologically, whereas there was minimal erythrocyte accumulation in extrahepatic tissue. Erythrocyte glutathione content was not altered by acetaminophen administration. It was concluded that hepatic sequestration of erythrocytes occurred to a sufficient extent to account for the precipitous fall in hematocrit observed.

Acetaminophen↗

Stimulation of albumin synthesis by keto analogues of amino acids.

(1) The effect of ketoanalogues of branched-chain amino acids on albumin synthesis was examined in two biological systems using the [14C]carbonate technique. (2)alpha-Ketocaproic acid, the ketoanalogue of leucine, was able to reverse the reduced synthesis rate observed when isolated livers, from well-nourished animals were perfused with blood from rats deprived of dietary protein for 48 h. (3) A mixture of ketoanalogues of the three branched-chain amino acids, leucine, isoleucine and valine, was able to increase albumin synthesis per unit dry liver weight to above normal levels when administered intragastrically to rats 16 h after partial hepatectomy.

Albumins↗

An animal model of fulminant hepatic failure: a feasibility study.

An attempt was made to produce animal model of fulminant hepatic failure in the pig by intragastric administration of acetaminophen (N-acetyl-p-aminophenol). The effect of varying doses was observed in phenobarbital-pretreated and untreated animals. Assessment of optimal dose was made in terms of duration of survival and coma in animals exhibiting biochemical and histological evidence of liver necrosis. Significant liver necrosis was observed in enzyme-induced pigs only, whereas in the noninduced pigs respiratory arrest was considered a likely cause of death. Although liver necrosis occurred consistently at a dose of 0.5 to 1.1 g per kg of acetaminophen in phenobarbital-pretreated animals, survival time and coma duration were unpredictable. Only one-fifth of the total number of phenobarbital-pretreated pigs administered acetaminophen in this dose range fulfilled the prescribed criteria for a satisfactory model. There was a good correlation between survival time and duration of coma, although survival time did not correlate with acetaminophen dose, or with any of the following: peak plasma acetaminophen levels, thrombocytopenia, fall in hematocrit or fibrinogen, or alteration in other biochemical parameters. In addition to the unpredictable duration of survival and coma, the occurrence of acute anemia in 60% of the enzyme-induced animals was a major detraction from the possible usefulness of this model to evaluate various therapeutic regimes.

Acetaminophen↗

Jaundice in severe bacterial infection.

Thirty patients are described who developed jaundice during the course of severe bacterial infection. Although the infecting organism was variable, as was the site of infection, the patients were generally ill and pyrexial. The group had a very high mortality rate (43%). A positive blood culture was obtained in 11 patients. Biochemical abnormalities noted were those of an increased concentration of conjugated bilirubin in the serum with only a modest increase in alkaline phosphatase and transaminase levels. Serum cholesterol was found to be normal. The mean serum urea level was significantly elevated, as were creatine phosphokinase and lactic dehydrogenase. Most patients exhibited a neutrophil leukocytosis and an elevated sedimentation rate, and the mean hemoglobin level was low. Liver histology was studied in 13 patients. There was evidence of mild bile stasis in 5 and moderate bile stasis in 2. Findings were otherwise nonspecific and were characterized by fatty change and/or inflammatory cells in the portal areas. There was no correlation between degree or duration of juandice and prognosis, although all patients who died remained jaundiced until death. It is suggested that this syndrome is not one of true cholestasis in that all biliary substances were not shown to be elevated in the serum, but that it is rather a selective defect in the excretion of conjugated bilirubin.

Adolescent↗

Albumin synthesis and catabolism following partial hepatectomy in the rat. The effects of amino acids and adrenocortical steroids on albumin synthesis after partial hepatectomy.

Plasma albumin levels were measured in partially hepatectomized, sham operated and control rats. The levels fell in both the partially hepatectomized and sham operated groups; while the latter group returned to normal within a few days, the low plasma albumin in the partially hepatectomized animals was sustained. Albumin synthesis rates in the isolated perfused rat liver were measured in the three groups of animals at varying intervals after partial hepatectomy. There was a significant depression of albumin synthesis rate in terms of both liver and whole animal weights when compared to the sham operated and control animals. This depression was almost completely reversed by the addition of arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine added together to 10 times their normal plasma concentrations. The addition of hydrocortisone had no effect on the albumin synthesis rate after partial hepatectomy. Studies in vivo in the three groups of animals (partially hepatectomized, sham operated and control animals) revealed a fall in the albumin catabolic rate after partial hepatectomy coinciding with the fall in the albumin synthesis rate. An hypothesis whereby the amino acids may have their stimulatory effect is proposed.

Albumins↗

The retinal blood flow in diabetes.

Retinal blood flow was studied in 9 normal volunteers and 36 diabetic patients. The method used was based on the measurement of the mean transit time of flourescein in the superior temporal quandrant of the retina and on estimation of the vascular volume by measuring vessels diameters. The results showed that patients with mild or no retinopathy had significantly increased volume flow compared with normals, those with moderate retinopathy had a slight but not significant increase and those with severe retinopathy had blood flow similar to that found in normals. The mean transit time was reduced significantly in those with mild or no retinopathy, but was similar to normals in those with moderate and severe retinopathy. Following succesful pituitary ablation and photocoagulation retinal blood flow was reduced compared with pre-treatment studies.

Adult↗

Stimulation of albumin synthesis by amino acids following partial hepatectomy in the rat.

Albumin synthesis was measured, in vivo, in rats 16 hours after partial hepatectomy or after sham operation. When albumin synthesis was expressed in terms of whole body weight, partially hepatectomized rats synthesized significantly less than sham-operated rats. However, when albumin synthesis was expressed as a function of dry liver weight, the two groups synthesized similar amounts. Intragastric hyperalimentation with amino acids significantly increased albumin synthesis in partially hepatectomized rats.

Amino Acids↗

Hepatic complications of antituberculous therapy.

Drug hepatitis occurred in 0-32 per cent of 7492 patients receiving antituberculous therapy, while the overall incidence of drug reactions was estimated at 9 per cent. PAS was the most common cause of drug hepatitis among the 38 patients analysed. The clinical, biochemical and haematological picture of antituberculous drug hepatitis was found to be fairly uniform. However, the patients with definite PAS hepatitis had lower SGOT values than those in whom there was uncertainty whether PAS or INH was implicated. Premonitory symptoms were present in all but four patients before the onset of jaundice. One or more of the features associated with dry hypersensitivity reactions, such as fever, rashes, lymphadenopathy, arthralgia, leucocytosis, eosinophilia and atypical monocytes were present in 89 per cent of cases so that confusion with viral hepatitis seldom arose. Sensitization time was less than three months in all except three patients, who were considered to be suffering from viral hepatitis. While no patients with PAS hepatitis died, the overall mortality was 17 per cent. A review of the literature stresses the frequency of asymptomatic elevations of SGOT, the value of clinical surveillance during the early months of therapy and the importance of stopping all therapy immediately warning symptoms appear.

Aminosalicylic Acids↗