Biomedical subjects
Publications and source records attributed to N D Grace.
The efficacy of selenium dioxide (SeO2) was similar to sodium selenate (Na2SeO4 x 10H2O), in terms of increasing and maintaining blood Se concentrations, when administered orally twice daily to give 0.64 mg of Se/day to grazing dairy cows for 55 days.
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The efficacy of 100-day controlled release anthelmintic capsules containing Se for increasing and maintaining the Se status of lambs was evaluated. Capsules containing either 7.7 or 13.9 mg of Se increased the mean blood Se concentrations from 1.50 +/- 8.4 nmol/l in the unsupplemented lambs to 440 +/- 29.8 and 990 +/- 83.4 nmol/l respectively 100 days after their administration. Blood Se concentrations then declined to 250 +/- 21.5 and 380 +/- 50.1 nmol/l respectively by day 210. The addition of 13.9 mg of Se to a 100-day controlled release anthelmintic capsule is an effective method of protecting lambs from Se deficiency for at least 180 days.
Supplementing three alpacas with Cu as cupric sulphate (10 mg Cu/kg liveweight) as a single oral dose resulted in no change in the mean plasma Cu concentrations over 30 days while a single oral dose of cupric oxide needles (2.5 g) given to three alpacas caused a small but significant increase in the mean plasma Cu concentrations during days 10-30 following treatment. The mean plasma Cu concentrations of four untreated animals ranged from 4.2 to 5.9 micromol/l over the study. The Cu as cupric sulphate was excreted in the faeces within 5 days while the cupric oxide needles significantly elevated the faecal excretion for over 30 days.
Rickets was diagnosed in two weaner alpacas from a flock showing ill thrift and lameness during the winter of 1992. Both animals had abnormally shaped ribs with occasional healing fractures, irregular thickening of growth plates and metaphyseal haemorrhages. The mean serum phosphorus concentrations of the alpacas fell during June and July, even though lambs grazing the same pasture had normal serum phosphorus concentrations and the phosphorus concentration of the pasture was considered adequate. Vitamin D deficiency may also have contributed to the osteodystrophy. The alpacas had a thick fleece during the winter, and diurnal Vitamin D, synthesis resulting from solar irradiation is likely to have been minimal, especially considering the reduced sunshine hours recorded during the 1992 winter. Surviving alpacas recovered after treatment with monosodium phosphate and an oral Vitamin D supplement. It is possible alpacas are more susceptible to deficiencies of phosphorus and Vitamin D than other grazing animals in New Zealand.
Nonselective beta-adrenergic blockers (propranolol and nadolol) are effective in preventing initial variceal hemorrhage, although their influence on improving survival is less dramatic. There is no role for either sclerotherapy or prophylactic portosystemic shunts for the prevention of initial variceal hemorrhage. Both endoscopic therapy (sclerotherapy, esophageal variceal ligation) and nonselective beta-adrenergic blockers are effective in reducing the risk of recurrent bleeding related to portal hypertension; however, there are significant numbers of failures with both approaches, and the effect on survival is less impressive. Randomized controlled trials evaluating each of these therapeutic options are reviewed in this article.
Although bleeding from esophagogastric varices remains a major cause of morbidity and mortality in patients with cirrhosis, recent advances in treatment show promise. Sclerotherapy is the accepted therapy for control of acute variceal bleeding. Endoscopic ligation of varices may be a reasonable alternative, with potentially fewer side effects. Pharmacological agents continue to have a role for initial treatment and as an adjunct to sclerotherapy. For patients who do not respond to medical management, either esophageal staple transection or the transjugular intrahepatic portasystemic shunt (TIPS) procedure is a reasonable rescue procedure and may be preferable to emergency portasystemic shunts. Both long-term sclerotherapy and nonselective beta blockers are effective in reducing the incidence of recurrent bleeding, but they are only marginally effective in improving survival. Endoscopic variceal ligation is currently under evaluation as a potential alternative to sclerotherapy. For patients unresponsive to medical therapy, the decision regarding a surgical shunt or liver transplantation will depend on each patient's clinical status and acceptability as a transplant candidate. The TIPS procedure may be useful in preventing rebleeding for patients awaiting transplantation. Nonselective beta blockers are effective in reducing the risk of first variceal hemorrhage, which is the ultimate goal of therapy, but they have shown only minimal benefit for survival. Shunt surgery and sclerotherapy are not indicated for prophylactic treatment. Future research will involve better identification of patients at high risk for variceal hemorrhage and evaluation of combinations of pharmacological and endoscopic therapies to prevent bleeding and to improve survival.
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.
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.
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.
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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.
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.
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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.
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)
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)