Portal hypertension and variceal bleeding: an AASLD single topic symposium.
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Clinical Trials as Topic↗
Biomedical subjects
N D Grace
Publications and source records attributed to N D Grace.
The effect of injectable barium selenate on the selenium status of horses on pasture.
AIM: To examine the effect of intramuscular barium selenate on the blood selenium concentration of horses with marginal selenium status. METHODS: Eighteen mares were assigned to one of six groups. The mares in groups 1-4 received barium selenate at 0.5, 0.75, 1.0 and 1.5 mg Se/kg, respectively, injected into the right pectoral muscle mass. The mares in group 5 received sodium selenate at 0.05 mg Se/kg orally at 8-week intervals. The mares in group 6 were left untreated. Blood samples were collected at 0, 1, 2, 5, 10, 30, 60, 90, 120, 180, 240, 300 and 360 days after the initial treatment for assay of whole blood and plasma selenium. Injection site reactions were recorded on each sampling date. RESULTS: Treatment with barium selenate at each dose rate significantly increased whole blood, plasma and blood cell selenium concentrations when compared to no treatment or oral treatment with sodium selenate, and maintained group mean whole blood selenium concentrations in the adequate range (>1600 nmol/l) until the end of the experimental period of 1 year. The severity of injection site reactions increased with dose rate but was considered acceptable alt the lower dose rates used. CONCLUSION: The injection of barium selenate placed aseptically at a deep intramuscular site was efficacious in correcting the selenium status of mares grazing pasture with a selenium content of 0.01-0.07 mg/kg DM. However, some swelling and fibrosis at the injection site was apparent at all dose rates used. CLINICAL RELEVANCE: There is currently no long-acting selenium supplementation product licensed in New Zealand for use in horses. Barium selenate promises to provide a useful method for selenium supplementation for horses, with an effective duration of at least 1 year following a single injection.
Journal Article↗
The efficacy of a subcutaneous injection of soluble Vitamin B12 in lambs.
AIMS: To assess the efficacy of a soluble Vitamin B12 injection in lambs by measuring changes in the serum and liver Vitamin B12 concentrations. METHODS: Thirty-six lambs were injected subcutaneously with 2 mg of soluble Vitamin B12 while another group of 36 served as untreated controls. Blood and liver biopsy samples for Vitamin B12 determinations were collected just before the injection and at days 1, 2, 5, 8, 16, 24, 30 and 45. RESULTS: The serum Vitamin B12 concentrations of the Vitamin B12 treated lambs increased rapidly compared to the untreated lambs. Concentrations peaked at day 2, decreased rapidly to day 8, and then decreased more slowly until day 24 when there were no longer differences between the groups. Liver Vitamin B12 concentrations of the Vitamin B12 treated lambs were significantly greater over days 8-24. CONCLUSION: A subcutaneous injection of 2 mg of soluble Vitamin B12 was effective in increasing and maintaining the Vitamin B12 status of lambs for about 24 days. CLINICAL SIGNIFICANCE: This Vitamin B12 product is only effective for preventing cobalt deficiency in lambs for about 4 weeks.
Journal Article↗
Effect of copper supplementation on copper status of pregnant mares and foals.
Pregnant Thoroughbred mares (n = 21) were grazed on tall fescue pasture containing 4.4-8.6 mg Cu/kg dry matter (DM). Twelve mares were supplemented with approximately 0.5 mg Cu/kg liveweight (LW)/day as copper sulphate for the final 13-25 weeks gestation. Plasma copper concentration declined during the third trimester for all mares and was not affected by copper supplementation. Liver copper concentration of mares and foals was determined when the foals were 4-10-days-old. Copper supplementation of the mares tended to increase mare liver copper concentration (P<0.08) and increased foal liver copper concentration (P<0.01). There was a significant relationship between mare and foal liver copper concentration (P<0.001, r2 = 0.7). Increasing the copper intake of mares is effective in enhancing the copper status of foals.
Analysis of Variance↗
Effect of copper supplementation on the copper status of pasture-fed young Thoroughbreds.
The effect of copper supplementation of pasture fed mares and foals on the copper status of the foals, in terms of plasma, soft tissue and bone copper concentrations and caeruloplasmin activity, was investigated. Twenty-one Thoroughbred foals from either control mares (n = 9), or copper-supplemented mares (n = 12) were divided randomly into control (pasture only, n = 10) or supplemented (pasture and oral copper sulphate, n = 11) groups. The pasture diet was grazed by all animals, and contained 4.4-8.6 mg Cu/kg dry matter (DM). The copper supplement for the mares contained copper sulphate equivalent to 0.5 mg Cu/kg liveweight (LW)/day. This daily dose was converted to allow administration as a thrice weekly dose (i.e. multiplied by 7/3) which was given for 13-25 weeks prior to foaling. The supplemented foals, also dosed 3 times a week, received 0.2 mg Cu/kg LW/day at age 21 days, which was increased to 0.5 mg Cu/kg LW/day at 49 days and was continued at this level until euthanasia at 150 days. Foal plasma copper concentration and caeruloplasmin activity increased from birth to 21 days post partum and then plateaued at a concentration similar to the mare, but the rise in these indices was not affected by copper supplementation of the mare or foal. Copper supplementation of the foal increased foal liver copper concentration at 150 days (P<0.03). Copper intake of diets containing approximately 8-28 mg Cu/kg DM is well reflected by liver copper concentration, but is poorly reflected by bone, other soft tissue copper concentrations and circulating copper status indices.
Administration, Oral↗
Effect of copper supplementation on the evidence of developmental orthopaedic disease in pasture-fed New Zealand Thoroughbreds.
The effect of copper status on the evidence of bone and cartilage lesions was investigated in 21 Thoroughbred foals. The foals and their dams were grazed on pasture containing 4.4-8.6 mg Cu/kg dry matter (DM). Four treatment groups were created by randomly allocating mares and their foals to either copper supplemented (0.5 mg Cu/kg liveweight (LW)/day), or control (pasture only) groups. This experimental design allowed the effect of copper supplementation of mare and foal to be examined independently. Parameters of bone and cartilage development were assessed in the foals both in vivo, and at post mortem at approximately age 150 days. Mare copper supplementation significantly (P<0.01) decreased radiographic indices of physitis in the distal third metatarsal bone of the foals at 150 days, and the prevalence of articular cartilage lesions (P<0.05). Articular cartilage lesions were minor in all foals, with no evidence of clinical developmental orthopaedic disease (DOD) in vivo, with the exception of minor radiographic changes assessed at post mortem. Copper supplementation of the foal had no effect on any of the bone and cartilage parameters. Copper supplementation of the mares did not abolish DOD in the growing foals, emphasising the probable multifactorial nature of this condition. However, mare supplementation may be a useful treatment regime on a farm where the incidence and severity of DOD are of concern.
Analysis of Variance↗
Prevalence of hereditary hemochromatosis in a Massachusetts corporation: is Celtic origin a risk factor?
The prevalence of homozygous hereditary hemochromatosis (HHC) is estimated at 1:250 in Caucasian adults. Little is known about ethnic subpopulations that might be at increased risk for this disease. HLA data have suggested a Celtic origin for HHC. Screening for HHC was offered to all employees of the Massachusetts Polaroid Corporation. Participants with a transferrin saturation of >55% or >45% and an elevated serum ferritin concentration on two screenings were referred for liver biopsy. The diagnosis of HHC was based on histological criteria, quantitative hepatic iron determination, hepatic iron index, and the phlebotomy requirement for iron depletion. Participants completed a questionnaire regarding their ethnic background. Two thousand two hundred ninety-four employees were screened, and 5 cases of HHC were detected. All 5 cases involved Caucasian men, yielding a prevalence of 1:395 for the Caucasian population. Four of the 5 cases were of 100% British-Irish ancestry based on the country of origin of their grandparents. Additional analysis revealed that the majority of grandparents of all 4 individuals came from Ireland or Wales. The exact two-tailed trend test showed a significant association of HHC with Celtic background (P = .012). The estimated cost of screening per patient identified was $18,041. Polaroid Corporation has a high representation of employees of British-Irish ancestry. Our data suggest that they are at high risk for developing HHC. A significant association of HHC with Celtic ancestry was found in this subpopulation, supporting the concept of a Celtic origin for this disease.
Adult↗
Pharmacologic therapy of portal hypertension and variceal hemorrhage.
Patients with large esophageal varices who are deemed compliant and have no contraindications to beta-blocker therapy should be started on nonselective beta-adrenergic blockers (Fig. 5). The dose should be titrated to a 25% decrease in resting heart rate, a resting heart rate of 55 to 60 beats per minute, or development of symptoms, in which case the dose should be decreased until the patient's symptoms abate. If available, measurements of the HVPG at baseline and 3 months can be very helpful in ascertaining the response to treatment and in making the appropriate adjustments (e.g., adding a second drug). Sclerotherapy or endoscopic variceal ligation are the preferred therapies for treatment of acute esophageal variceal bleeding. Concomitant use of vasoactive drugs can supplement endoscopic treatment. They offer the advantage of early administration as soon as the diagnosis is suspected while awaiting endoscopy. Unlike endoscopic treatment, they decrease portal pressure and are the only established treatment for nonvariceal sources of bleeding related to portal hypertension. Once the index bleed is controlled, the patient should be started on treatment to reduce the high risk of recurrent variceal hemorrhage (Fig. 6). For patients with well-compensated cirrhosis, pharmacologic therapy may be desirable. For less compliant patients or patients with decompensated cirrhosis, an endoscopic technique, such as variceal ligation, may be preferable. Combinations of pharmacologic agents or pharmacologic agents and endoscopic procedures may offer hope for better control, but their efficacy needs to be demonstrated in RCTs. For patients who rebleed despite maximal pharmacologic or endoscopic therapy, a TIPS procedure, surgically created shunt, or liver transplantation should be considered, with the decision based on the patient's condition and the local availability of these options.
Esophageal and Gastric Varices↗
TIPS: the long and short of it.
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Humans↗
The portal pressure response to beta-blockade is greater in cirrhotic patients without varices than in those with varices.
BACKGROUND & AIMS: Nonselective beta-blockers are effective in reducing portal pressure in cirrhotic patients. However, this beneficial effect is highly variable and may depend on the extent of portal system collateralization. The aim of this study was to compare portal pressure response with timolol, a nonselective beta-blocker, in cirrhotic patients with and without varices. METHODS: Portal and systemic hemodynamics were measured before and after a single oral dose of 10 mg of timolol in 50 patients with cirrhosis and portal hypertension, 15 with and 35 without esophageal varices. RESULTS: Timolol significantly decreased portal pressure in all patients (mean reduction, 20% +/- 13%; P < 0.0001). The reduction in hepatic venous pressure gradient was greater in patients without varices (-24% +/- 14%) than in those with varices (-12% +/- 8%) (P < 0.01). A decrease in the hepatic venous pressure gradient of <12 mm Hg was achieved in 7 of 12 (58%) patients without varices and a baseline pressure gradient of <12 mm Hg, but only in 3 of 15 patients with varices (20%) (P < 0.01). CONCLUSIONS: Timolol is effective in reducing portal pressure in cirrhotic patients, more so in patients without varices, suggesting that nonselective beta-blockers will be more effective in the treatment of portal hypertension when administered at early stages, before the development of varices.
Aged↗
Utility of hepatic iron index in American patients with hereditary hemochromatosis: a multicenter study.
BACKGROUND & AIMS: A hepatic iron index (hepatic iron concentration divided by age) of more than 1.9 has been proposed as useful to identify patients with homozygous hereditary hemochromatosis (HHC). There are limited data on the diagnostic use of the hepatic iron index in patients with HHC in the United States. This study evaluated the hepatic iron index in the diagnosis of HHC in a multicenter U.S. study. METHODS: Hepatic iron concentration was measured in 509 patients undergoing liver biopsy. The diagnosis of HHC was made using clinical, biochemical, and histopathologic criteria. RESULTS: Fifty-five patients met criteria for HHC; hepatic iron index was > 1.9 in 51 of 55 (93%) patients with HHC but in none of 454 patients with other liver diseases; hepatic iron concentration was > 71 mumol/g dry weight in 54 of 55 patients with HHC but only 1 of the other 454 patients. CONCLUSIONS: A hepatic iron index of > or = 1.9 can identify most U.S. patients with HHC but is < or = 1.9 in 7%. A "threshold" hepatic iron concentration of 71 mumol/g can almost always distinguish patients with HHC from patients with other liver diseases and may be a useful adjunct to the hepatic iron index in the diagnosis of HHC in the diverse U.S. population.
Adult↗
Relationships between blood Se concentrations and milk somatic cell counts in dairy cows.
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Letter↗
Evaluation of intraruminal devices for combined facial eczema control and trace element supplementation in sheep.
Intraruminal devices containing zinc oxide are very effective in preventing facial eczema in sheep. In the present study such devices augmented with various amounts of selenium and cobalt have been evaluated for their ability to improve the Se and CO status of pregnant ewes, as reflected by changes in blood Se and serum Vitamin B12 concentrations. Devices containing 16.4 mg of Se (as sodium selenate) and 20.4 mg of Co (as cobalt sulphate) were effective in increasing and maintaining elevated blood Se concentrations for at least 84 days and serum Vitamin B12 for 42 days. Such devices will therefore prevent trace element deficiencies in sheep as well as providing protection against facial eczema.
Journal Article↗
Liver biopsy techniques for adult horses and neonatal foals to assess copper status.
OBJECTIVE: To evaluate standing, percutaneous, ultrasound-guided, transthoracic liver biopsy in mares, and transabdominal laparoscopically-guided, liver biopsy under general anaesthesia in foals, as techniques for obtaining tissue for assessment of copper status. The techniques were evaluated with respect to ease of use and effect on the animal. PROCEDURE: Twenty of 24 Thoroughbred mares and 21 of their foals were biopsied. The animals were part of a larger study of the effect of copper supplementation on copper status and the prevalence of developmental orthopaedic disease. Livers were also collected from unrelated horses and sampled to investigate the variability in the distribution of copper in liver tissue. RESULT: The biopsy technique caused no lasting effect on the mares, but there was an increased risk of viscus penetration associated with taking multiple biopsy cores. The use of ultrasonography to scan the target area for the liver identified four cases that were not appropriate candidates for liver biopsy, because of large intestine being located in the biopsy area. In the foals there were no serious postoperative adverse effects, nor was there any evidence of problems caused by the procedure when the abdomen was examined post-mortem at 5 months of age. In livers collected to investigate the variability of copper concentration, copper appeared to be relatively evenly distributed through the liver. CONCLUSION: Standing, percutaneous, ultrasound-guided, transthoracic liver biopsy in mares, and transabdominal, laparoscopically-guided, liver biopsy under general anaesthesia in foals are convenient procedures for obtaining liver tissue for assessing copper status in horses. The use of ultrasound to identify liver tissue is recommended, especially in older mares.
Animals↗
Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. American College of Gastroenterology Practice Parameters Committee.
UNLABELLED: Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When data are not available that will withstand objective scrutiny, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care, which are inflexible and rarely violated. Given the wide range of choices in any health care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its practice parameters committee. These guidelines are also approved by the governing boards of American College of Gastroenterology and Practice Parameters Committee. Expert opinion is solicited from the outset for the document. Guidelines are reviewed in depth by the committee, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time. The following guidelines are intended for adults and not for pediatric patients. OBJECTIVE: To develop practice guidelines for the management of gastrointestinal bleeding in adult patients with cirrhosis and portal hypertension. METHOD: Randomized controlled trials published through October of 1993 were evaluated by members of the American College of Gastroenterology Practice Parameters Committee. Each paper was reviewed by three members of the committee and rated for quality of design by predetermined criteria. Meta-analysis of the studies for each treatment were evaluated for both outcome and quality of design and formed the basis for recommendations for treatment. Randomized controlled trials published between October of 1993 and August of 1995 have been added to update and modify the recommendations. The reader is referred to an excellent article by D'Amico et al. (The treatment of portal hypertension: A meta-analytic review. Hepatology 1995;22:332-354), which presents most of the meta-analyses reviewed by this committee. CONCLUSIONS: Once esophageal varices have been established by endoscopy as the site of bleeding, either sclerotherapy or endoscopic variceal ligation should be performed to control the bleeding episodes. Concomitant use of vasoactive drugs lowers portal pressure, potentially offers the endoscopist a clearer field in which to work, and is the only noninvasive treatment for nonesophagogastric variceal sites of bleeding related to portal hypertension. For patients failing medical therapy, the transjugular intrahepatic portasystemic shunt procedure is a reasonable alternative to an emergency surgically created shunt. Nonselective beta-adrenergic blockers are the only proven therapy for prevention of first variceal hemorrhage. Both nonselective beta-adrenergic blockers and endoscopic variceal ligation (which has replaced sclerotherapy for this indication) are effective in reducing the risk of recurrent variceal bleeding. For patients failing these approaches, selective or total shunts or, in selected patients, liver transplantation are appropriate rescue procedures.
Acute Disease↗
An update on iron metabolism: summary of the Fifth International Conference on Disorders of Iron Metabolism.
HHC is the most common inherited metabolic disease among the white population worldwide, with a gene frequency of about 10% and a frequency of homozygosity of about 1 of 250. Many patients harbor a common haplotype of informative markers on chromosome 6p2l.23, suggesting a strong founder effect exerted by a common Celtic ancestor. With the advent of screening tests (serum Tf saturation, fe), many subjects with HHC are being identified before development of cirrhosis or diabetes mellitus, and early detection is important because prompt and vigorous iron reduction prevents development of such complications and assures normal life expectancy. The HIC can be estimated as accurately by specialized magnetic resonance imaging or susceptometric measurements as by chemical measurements on liver biopsy specimens. However, biopsy specimens retain value for showing fibrosis/cirrhosis and dysplastic hepatocytes, both of which increase risks of HCC development. There is growing evidence that iron in the liver plays an important role in non-HHC diseases, such as alcoholic liver disease, chronic viral hepatitis, and porphyria cutanea tarda. The complicated, manifold roles of iron in pathogenesis of the latter disorder include enhancement of production and irreversible oxidation of uroporphyrinogen, as well as formation of an inhibitor targeted specifically at hepatic uroporphyrinogen decarboxylase. The nature of the gene and gene product that are abnormal in HHC remain elusive, despite the intense efforts of several investigative groups. The search has been hampered by a dearth of informative markers in HHC patients in the relevant region of chromosome 6p. Note added in proof: The cloning of a candidate gene, the mutation of which may perhaps cause HLA-linked hemochromatosis, has just been reported (Feder et al: A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature (Genetics) 1996;399-408). These workers identified a 250-kb region move than three megabases telomeric of the MHC that was identical in 85% of chromosomes of HHC patients. Within this region, they identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations one of which is predicted to inactivate this class of proteins. 83% of 178 patients were homozygous for this mutation (Cys 282Tyr). This variant was also found on 3.2% of control chromosomes, as would be expected for such a common disorder. Functional studies are awaited with great interest.
Congresses as Topic↗
Pemoline-induced autoimmune hepatitis.
We present a case of pemoline-induced autoimmune hepatitis in a 46-yr-old woman who received the drug for management of her multiple sclerosis. The autoimmune nature of the hepatitis is based on elevation of her anti-nuclear antibodies, anti-thyroid antibodies, IgA, and IgM globulins. These features of autoimmunity disappeared with normalization of her liver-associated enzymes and have remained negative for at least 6 months after completion of prednisone therapy.
Antibodies, Antinuclear↗
Liver transplantation for hemochromatosis: an ironic dilemma.
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Hemochromatosis↗