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Biomedical subjects

N D Grace

Publications and source records attributed to N D Grace.

At least 19 recordsLinked to original sources
PubMed1992

Prevention of initial variceal hemorrhage.

Results from prospective controlled trials do not justify the use of either prophylactic shunt surgery or sclerotherapy for the prevention of initial variceal bleeding. Use of nonselective beta-adrenergic blockers has been shown to reduce significantly the risk of first variceal hemorrhage, but their effect on survival is marginal. Because only 25% to 40% of patients with cirrhosis and varices experience variceal bleeding, is it justified to place all patients with varices on beta-blocker therapy? The answer lies in the identification of a high-risk population (i.e., patients with large varices and endoscopic red color signs) and patients who can tolerate and will be compliant with therapy. The duration of therapy required is unknown and perhaps requires a lifetime commitment. Future research will involve the use of combinations of pharmacologic agents to reduce further portal pressure and perhaps the use of pharmacologic agents and sclerotherapy. The goal of a significant improvement in survival is yet to be obtained.

Adrenergic beta-Antagonists↗
PubMed1992

Arterioportal fistula: a role for pre-TIPSS arteriography and hepatic venous pressure measurements.

A 70-yr-old male presented with massive upper gastrointestinal bleeding secondary to esophageal varices. Because the bleeding was not controlled by sclerotherapy or vasopressin and nitroglycerin, the patient was evaluated for a transjugular intrahepatic portosystemic shunt. Preprocedure arteriography was performed because the etiology of the portal hypertension was uncertain. The arteriogram revealed a hepatic artery to portal vein fistula. Hepatic venous pressure measurements documented an elevated hepatic venous pressure gradient, which diminished dramatically upon embolization of the fistula. Rebleeding from the varices was associated with reestablishment of the fistula via collaterals and elevation of the hepatic venous pressure gradient. The case is presented to establish a role for arteriography prior to transjugular intrahepatic portosystemic shunting, especially in patients with unexplained portal hypertension, and to establish the potential value of hepatic venous pressure measurements in the treatment of arterioportal fistulas.

Aged↗
PubMed1991

Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial. The Boston-New Haven-Barcelona Portal Hypertension Study Group.

To assess the effectiveness of propranolol in the prevention of initial variceal hemorrhage, a double-blind, randomized trial was carried out in three centers. Patients with cirrhosis (78% alcoholic), hepatic venous pressure gradients greater than 12 mm Hg and endoscopically proven esophageal varices were randomly assigned to propranolol (51 patients) or placebo (51 patients). Of the 102 patients, 58% were Child's class A, 34% were Child's class B and 8% were Child's class C. Daily dosage was determined by the administration of progressively increasing doses of propranolol with the hepatic vein catheter in place to achieve a 25% decrease in hepatic venous pressure gradient, a decrease in hepatic venous pressure gradient to less than 12 mm Hg or a decrease in resting heart rate to less than 55 beats/min. During a mean follow-up period of 16.3 mo, 11 patients in the placebo group (22%) bled from esophageal varices compared with 2 in the propranolol group (4%) during a mean period of 17.1 mo (p less than 0.01). Three additional patients (6%) in the placebo group bled from portal hypertensive gastropathy compared with none in the propranolol group. Propranolol appeared effective in preventing bleeding from large varices. Eleven deaths (22%) occurred in the placebo group compared with eight deaths (16%) in the propranolol group (NS). The mean dose of propranolol was 132 mg/day, and the median dose was 80 mg/day. Using a compliance index (pill count, clinic attendance, alcohol and propranolol levels and alcohol history), 81% of the propranolol patients and 77% of the placebo patients were considered compliant. Complications severe enough to require cessation of therapy occurred in eight patients (16%) in the propranolol group and four in the placebo group (8%) (NS). We conclude that propranolol effectively prevents the first variceal hemorrhage in patients with alcoholic cirrhosis and large esophageal varices but does not improve survival.

Blood Pressure↗
PubMed1990

Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage.

In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 +/- 4.2 to 15.7 +/- 3.4 mm Hg; P less than 0.05) but not in patients receiving the placebo (19.6 +/- 6.8 to 17.5 +/- 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P less than 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranolol-treated; P less than 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension.

Adult↗
PubMed1990

A hepatologist's view of variceal bleeding.

Patients with cirrhosis and esophagogastric varices have a 25% to 33% risk of initial variceal bleeding, a risk of up to 70% for recurrent variceal bleeding, and an associated mortality of up to 50%. Based on a review of prospective randomized trials, control of acute variceal bleeding should involve vasopressin plus nitroglycerin as indicated for minor bleeding episodes, sclerotherapy for more severe bleeding episodes, and staple transection of the esophagus for patients who do not respond to these initial measures. Emergency portasystemic shunt surgery cannot be recommended at this time. For prevention of recurrent variceal hemorrhage, the data support the use of nonselective beta-adrenergic blockers (propranolol or nadolol) for patients with good liver function (Child's class A and B) and the use of chronic sclerotherapy to obliterate esophageal varices for patients with decompensated cirrhosis (Child's class C). Surgical procedures should be reserved for failures of medical management. The use of beta-adrenergic blockers offers the most promise for prevention of initial variceal bleeding.

Acute Disease↗
PubMed1989

Iron overload complicating sideroblastic anemia--is the gene for hemochromatosis responsible?

Idiopathic hemochromatosis is a hereditary disease that is associated with human leucocytic antigens A3, B7, and B14. A genetic association between human leucocytic antigen-linked hemochromatosis and idiopathic refractory sideroblastic anemia has been suggested that may predispose some patients with idiopathic refractory sideroblastic anemia to develop gross iron overload. Study of the family of a patient with idiopathic refractory sideroblastic anemia and hemochromatosis revealed that 2 of 5 first-degree relatives had significant elevations of serum ferritin, and a shared human leucocytic antigen haplotype, supporting the concept that patients with idiopathic refractory sideroblastic anemia and significant iron overload have at least one allele for hemochromatosis.

Aged↗
PubMed1989

Kinetic aspects of calcium metabolism in lactating sheep offered herbages with different Ca concentrations and the effect of protein supplementation.

1. Two experiments are described in which kinetic aspects of calcium metabolism were studied in housed lactating sheep consuming different fresh herbage species. The importance of protein supply was also investigated. 2. In Expt. 1, two groups (n 4) were offered, ad lib., a freshly cut ryegrass (Lolium perenne L.)-white clover (Trifolium repens L.) pasture containing 5.48 g Ca/kg dry matter (DM). One group was supplemented daily with 100 g protected casein. A third group (n 4) was offered, ad lib., freshly cut oats-Tama ryegass (Lolium multiflorum L.) herbage which had a lower Ca content of 3.07 g Ca/kg DM. Stable Ca and nitrogen balances were carried out during the first 7 weeks of lactation. At this stage 180 microCi 45Ca were administered for Ca kinetic studies. 3. In Expt 2, eight sheep were offered, ad lib., a fresh ryegrass-white clover pasture, and paired on the basis of their udder size. One member of each pair was supplemented daily with 100 g casein via the abomasum and the amount of milk removed was equalized between pairs. Ca and N balance (12 d) and) and Ca kinetic studies (280 microCi 45Ca) were carried out during weeks 2 and 5 of lactation. 4. Rate of absorption of Ca increased, while rate of Ca secretion in milk and resorption from bone decreased as lactation progressed. Ca balances changed from negative to positive as lactation progressed in sheep offered ryegrass-white clover, but, while improving, were always negative in sheep offered oats-Tama ryegrass. Protein supplementation increased (18%) milk production of the ewes in Expt 1 and their retention of N in Expt 2. 5. The proportion of utilized Ca derived from the diet, as opposed to the skeleton, tended to increase as a result of protein supplementation. 6. Availability of Ca from ryegrass-white clover ranged from 0.19 to 0.32, even though only 50% of the net Ca requirement was derived from the diet. Availability of Ca from the oats-Tama ryegrass diet was similar, though in this case less than 20% of the net Ca requirement was derived from the diet. It was concluded that availability of Ca from forage diets may be lower than previously anticipated. 7. Faecal endogenous loss ranged from 16 to 40 mg Ca/kg body-weight per d, and was similar on both diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1989

Faecal endogenous loss of calcium in young sheep.

1. Two groups of eight 6-7-month-old wether lambs were offered either a frozen ryegrass (Lolium perenne L.)-white clover (Trifolium repens L.) pasture or a ryegrass-white clover hay, containing 12.1 and 6.4 g calcium/kg dry matter (DM) respectively. Within groups the amounts offered to individual sheep ranged from 0.5 to 2.0 times the estimated maintenance energy requirements. 2. A single intravenous injection of 150 microCi 45Ca as CaCl2.2H2O, and stable balances were used to determine absorption, faecal endogenous loss and balance of Ca. 3. Faecal endogenous loss of Ca increased by 1.2 mg/kg body-weight (W) per d with each g/kg W per d increase in DM intake regardless of the diet. At any DM intake the mean faecal endogenous loss was 5.5 mg/kg W per d higher in the sheep offered the frozen herbage diet when compared with those on the hay diet. At any Ca intake the mean faecal endogenous loss was 6.9 mg/kg W higher in sheep offered the hay diet compared with those on the frozen herbage. 4. At feeding levels of about 1.5-2 times the estimated maintenance energy requirement the observed faecal endogenous loss of Ca ranged from 35 to 50 mg/kg W per d, which is two- to threefold greater than the present estimate of the Agricultural Research Council (1980) of 16 mg/kg W per d.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Some effects of sulphur intake on molybdenum metabolism in sheep.

1. To investigate the effects of sulphur intake on molybdenum metabolism in sheep, ewes were given intakes of 0.3 or 3.5 mg Mo and 0.98, 1.33, 1.73 or 3.23 g S/d in a 2x4 factorial experiment with two replicates lasting 35 d. 99Mo with 0.1 mg carrier Mo was infused intravenously for the last 14 d and, when 99Mo concentrations in urine and faeces had attained plateaux (days 11-14), stable Mo and 99Mo balance trails were conducted; samples of blood and rumen contents were taken principally for studies of Mo distribution. 2. Increases in S intake caused the following changes in Mo metabolism; absorption decreased, urinary and faecal endogenous excretion decreased and retention increased; Mo concentrations in rumen contents decreased but the predominant association with the solid phase was unaffected; Mo concentrations in plasma decreased, but a higher proportion was associated with the protein fraction; Mo in protein-free plasma became apparently less ultrafiltrable at the glomerulus. 3. The pattern of response to S for each factor was generally curvilinear, the first increment in S intake having by far the greatest effect. The effect of S was generally greatest at the higher Mo intake. 4. It is suggested that the manifold effects of S on Mo metabolism are related to a common interaction in the rumen leading to the formation of Mo-complexes, possibly thiomolybdates, which are poorly absorbed but even more poorly excreted.

Animals↗
PubMed1979

Gastroesophageal reflux and bleeding esophageal varices.

The incidence of gastroesophageal reflux was evaluated with the use of a pH probe in 12 patients with cirrhosis and recent variceal hemorrhage and in 15 healthy control subjects. Short episodes of reflux occurred in 42% of the patients and in 47% of the controls. During an observation period of 1 hr, the cumulative duration of reflux was similar in patients (2.5 +/- 1.3 min) and controls (3.1 +/- 1.4 min). Mean lower esophageal sphincter pressures were normal in both groups but did not show a significant correlation with the duration of reflux. These data support previous observations that gastroesophageal reflux dose not appear to be a contributing factor in the development of variceal hemorrhage.

Adult↗
PubMed1978

Lower esophageal sphincter pressure and serum gastrin levels after mapped antrectomy.

We investigated the effect of mapped antrectomy with gastroduodenostomy on serum gastrin levels in fasting patients and resting lower esophageal sphincter (LES) pressure. Serum gastrin levels in fasting patients were lower in those who had an antrectomy without vagotomy (P less than .05) as compared to control subjects or patients with antrectomy and vagotomy. Resting LES pressure was similar in patients and controls and was not affected by the presence or absence of vagotomy. These findings suggest that (1) mapped antrectomy and gastroduodenostomy without vagotomy are followed by a decrease in serum gastrin and (2) resting LES pressure is not affected by mapped antrectomy and a decrease in serum gastrin level.

Adult↗
PubMed1978

[Unusual esophageal motility disorder (author's transl)].

A 31 year-old female initially presented with clinical features consistent with achalasia, which were relieved by the Heller procedure. Several years later manometric tracings excluded the diagnosis of achalasia, and suggested a motility disorder of the esophageal body. A long esophageal myotomy was performed and was followed by a marked improvement in symptoms and a normalization of the manometric tracing. Multiple histologic sections from the surgical specimen revealed the absence of ganglion cells, a feature not previously described in motor disorders other than achalasia. These findings suggest that classification of esophageal motility disorders on the basis of manometric and histologic findings might not be possible and that surgical treatment should be directed towards the predominant symptoms.

Adult↗
PubMed1976

Lower esophageal sphincter pressure and serum motilin levels.

The gastrointestinal hormone motilin has recently been proposed as having a physiological role in the determination of lower esophageal sphincter (LES) strength. The present study was performed to evaluate the effect of gastric alkalinization of LES pressure and serum motilin levels. Instillation of 0.1N NaHCO3 into the stomach resulted in a significant increase in LES pressure (P less than 0.01) without affecting serum motilin levels. No correlation was found between fasting serum motilin levels and resting LES pressure (r = -0.31). These observations do not support the theory that LES pressure increases during gastric alkalinization are mediated through motilin release.

Adult↗
PubMed1976

Does lower esophageal sphincter incompetency contribute to esophageal bleeding?

The purpose of this study is to determine whether lower esophageal sphincter (LES) incompetency is a common occurrence in patients with liver cirrhosis and contributes to the development of variceal bleeding. Resting LES pressure (17.8 +/- 1.1 mm Hg) in 35 patients with cirrhosis was similar to that of our control population (17.3 +/- 2.0 mm Hg). No differences were found among patients with ascites, variceal hemorrhage, or with different degrees of hepatic decompensation. In both patients and control subjects the LES responded with a significant pressure increase to gastric alkalinization. Symptoms and radiological evidence of gastroesophageal reflux were extremely uncommon in patients with liver cirrhosis. Based on these data it is unlikely that acid-pepsin regurgitation is a significant factor in the development of variceal hemorrhage.

Adult↗