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Biomedical subjects

J T Galambos

Publications and source records attributed to J T Galambos.

At least 19 recordsLinked to original sources
PubMed1991

A randomized, controlled trial of treatment of alcoholic hepatitis with parenteral nutrition and oxandrolone. I. Short-term effects on liver function.

The present studies were designed to provide careful measures of effects of oxandrolone, an anabolic steroid, intravenous nutritional supplementation, and the combination of these two treatments on liver functions, metabolic balances, nitrogen metabolism, and nutritional status in patients with moderate to severe alcoholic hepatitis. Of 43 patients originally recruited, 39 (19 men, 20 women) with typical clinical and laboratory features of alcoholic hepatitis (11 Child's-Pugh class B; 28 class C) were admitted to a metabolic unit and completed a 35-day three-phase protocol. Phase I was a 10-day baseline period of observation, during which routine and special quantitative tests of liver function (galactose and antipyrine metabolism), a 7-day elemental balance study, and a 15N, 13C-leucine metabolism study were done. Phase II was a 21-day treatment period during which patients were randomly assigned to receive one of four regimens: 1) standard therapy, consisting of abstinence, a balanced, nutritionally adequate diet, and multivitamins; 2) oxandrolone (20 mg orally four times a day) plus standard therapy; 3) nutritional supplementation, consisting of 2 L daily of 3.5% crystalline amino acids (in 5% dextrose), given by peripheral vein; or 4) a combination of oxandrolone and nutritional supplementation, along with standard therapy. Metabolic balances were repeated during phase II. Phase III was 2 or 3 days posttreatment, during which special studies of liver functions and volumes and leucine metabolism were repeated. All patients who completed phase I of study and were randomly allocated to one of the four treatment groups completed the subsequent two phases. Overall, with time, patients showed highly significant improvements in most clinical and laboratory features. For most standard laboratory tests (e.g., serum albumin, transferrin, prothrombin time) improvements were more marked in patients treated with nutritional supplementation and/or oxandrolone than in those given standard therapy alone. Liver volumes fell in all treatment groups, with greater improvement in those treated with nutritional supplementation. Improvements in galactose and antipyrine metabolism rates were significant only in those treated with nutritional supplementation or oxandrolone. Effects of treatments on metabolic balances, nitrogen metabolism, and measures of nutrition are described in this issue in a companion paper. We conclude that the addition of nutritional supplementation and oxandrolone to standard therapy of moderately severe or severe alcoholic hepatitis is well tolerated, and leads to more rapid improvement in the laboratory parameters measured.

Adult↗
PubMed1990

Endoscopic variceal sclerosis compared with distal splenorenal shunt to prevent recurrent variceal bleeding in cirrhosis. A prospective, randomized trial.

STUDY OBJECTIVE: To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis. DESIGN: A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months. SETTING: A private, tertiary-referral university hospital. PATIENTS: Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval. TREATMENTS: Endoscopic variceal sclerosis or distal splenorenal shunt. MEASUREMENTS AND MAIN RESULTS: Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P less than 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively). CONCLUSIONS: Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding.

Endoscopy↗
PubMed1990

Prevalence and prediction of osteopenia in chronic liver disease.

To obtain information on the prevalence and clinical and laboratory correlates of osteopenia in patients with chronic liver disease, we measured bone densities and 30 selected laboratory variables in 133 subjects (70 men, 63 women) with liver disease. Thirty-two had alcoholic liver disease, 18 had primary biliary cirrhosis, 16 had primary sclerosing cholangitis, 48 had other forms of cirrhosis (cryptogenic, posthepatic) and 19 had chronic hepatitis or fibrosis without cirrhosis. Bone densities of the lumbar spine and three sites of the proximal femur (neck, Ward's triangle, greater trochanter) were estimated by dual-photon absorptiometry. Bone densities at all sites were significantly correlated to one another (r = 0.4 to 0.9; 95% confidence intervals = 0.24-0.54 to 0.81-0.90; p less than 0.0001 for all). Compared with an age- and gender-matched reference group, patients with liver disease had highly significant decreases in bone densities (greater than 2 standard deviations below control values; p less than 0.0008 at all sites). Decreases were particularly marked (24% to 42%) at Ward's triangle, the site of the femoral neck particularly prone to fracture. The prevalence of decreased bone densities ranged from 10% to 56%, depending on the site studied and the nature of the liver disease. Among 30 laboratory variables studied, there were significant (p less than 0.05) correlations with bone densities at more than one site for urinary creatinine (r = 0.21, 0.25), urinary calcium (r = -0.18, -0.23), serum total alkaline phosphatase (r = -0.18, -0.27) and the liver-1 isozyme of serum alkaline phosphatase (r = -0.19, -0.26).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗
PubMed1990

Evaluation of patients with portal hypertension.

In order to select the most suitable management of portal hypertension, a full evaluation of the patient is desirable. The aspects studied should include the possible causes of portal hypertension and the disease and function of the liver, as well as the psychosocial aspects of this condition. The usual reason to investigate the presence and causes of portal hypertension is the detection of gastroesophageal varices. The estimated probability of bleeding from the varices and the cause of the varices should be investigated. If cirrhosis is detected, then its cause or mechanism should be clarified and the activity of the process estimated in semiquantitative terms. If therapy is available, it should be initiated. The evaluation of liver function is based on quantitative measurements of hepatocellular metabolic function (such as the galactose elimination capacity or antipyrine clearance), liver volume (weight), liver blood flow, and systemic hemodynamics (cardiac output index).

Cardiac Output↗
PubMed1990

Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease.

The major biological functions of S-adenosyl-L-methionine (SAMe) include methylation of various molecules (transmethylation) and synthesis of cysteine (trans-sulphuration). A stable double salt of SAMe has been found to be effective in intrahepatic cholestasis. The mechanism of its therapeutic effect is not fully understood but presumably involves methylation of phospholipids. Methylation of plasma membrane lipids may affect membrane fluidity and viscosity, which modulate the activities of a number of membrane-associated enzymes, for example, the activity of enzymes involved in Na+/Ca++ exchange (e.g. sarcolemmal vesicles), Na+/K+ adenosine triphosphatase (ATPase) [e.g. hepatocyte plasma membranes], and Na+/H+ exchange (e.g. plasma membranes of colonic cells). Recently, patients with cirrhosis were shown to have an acquired metabolic block in the hepatic conversion of methionine to SAMe. These patients, when administered conventional elemental diets, develop abnormally low plasma concentrations of cysteine and choline, 2 nonessential nutrients present in low concentrations in most elemental diets. These low concentrations probably reflect systemic deficiencies attributable to reduced endogenous syntheses of cysteine and choline caused by limited availability of hepatic SAMe. Such cirrhotic patients are often in negative nitrogen balance and have abnormal hepatic functions, which are corrected by cysteine and choline supplements. Noncirrhotic patients on parenteral elemental diets also become deficient in cysteine and choline. Consequently, these patients may require SAMe as an essential nutrient to normalise their overall hepatic transmethylation and trans-sulphuration activities.

Animals↗
PubMed1989

Ethanol: relative fuel value and metabolic effects in vivo.

A nasogastric formula infusion method was used to evaluate the steady-state fuel value of ethanol relative to that of glucose in eight chronically alcoholic men undergoing a 4- or 5-week balance experiment. Each subject received a maintenance infusion of the formula diet throughout the study. When control formula glucose (week 1) was isocalorically replaced with ethanol [week 2, 30% of kcal; week 3 or 4 (5-week experiment) 40% to 60% of kcal], the following was observed: weight loss; zero energy balance and reduced or negative balances of N, K, P, Mg, and Na; increased urinary urea N and 3-methylhistidine; lowered urinary C-peptide; no change in indirectly or directly measured thermal energy losses; and a blood level related rise in breath and urinary ethanol losses. All of these changes promptly reversed during the middle (week 3 in 5-week experiment) and final control weeks. Accounting for all diet-related energy losses (urine, breath, thermal), the fuel value of the ethanol-containing diet relative to the glucose control formula varied between 0.95 and 0.99, depending upon the blood alcohol level. Hence weight loss during short-term (seven-day) ethanol infusion is unrelated to overall negative energy balance, stems primarily from decrements in protein, minerals, and fluid, and may in part be mediated by the reduction in insulin secretion that accompanies switching from dietary glucose to ethanol.

Adult↗
PubMed1989

Sclerosing cholangitis: palliation with percutaneous cholangioplasty.

Fourteen patients with sclerosing cholangitis underwent percutaneous cholangioplasty and stent placement with balloon-angioplasty and biliary-drainage catheters. There was initial clinical improvement in 13 of the 14 patients; one patient did not improve and died 1 month after the procedure. One of the 13 survivors developed encephalopathy and received a liver transplant 9 months after cholangioplasty; during the 9 months before transplantation, serum bilirubin and alkaline phosphatase levels returned to normal, and pruritus decreased. Restenosis of a duct following stent removal prompted repeat cholangioplasty in five of the 13 patients. Four of these five patients benefited from repeat cholangioplasty, and the fifth underwent liver transplantation 10 months after the second cholangioplasty. The other seven of the 13 survivors became either asymptomatic (n = 3) or less symptomatic than before cholangioplasty (n = 4) and did not require repeat cholangioplasty or liver transplantation during 10-42 months of follow-up.

Adolescent↗
PubMed1988

Peliosis hepatis in a patient with marasmus.

Peliosis hepatitis is a rare disorder previously seen in tuberculosis and malignant disorders and now seen with anabolic steroid use or after renal transplantation. We report the first case of peliosis hepatis in a patient with marasmus and no previously reported predisposing condition. Of interest, the peliosis hepatis resolved rapidly (over 2-3 wk) as determined by computed tomography scan and the patient presented with a cholestatic enzyme pattern that resolved with development of the lesion.

Aged↗
PubMed1988

A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis.

We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites.

Amino Acids↗
PubMed1988

Management of variceal bleeding in patients with noncirrhotic portal vein thrombosis.

Since 1971, 70 patients have been seen at Emory University Hospital with gastroesophageal varices secondary to extrahepatic portal vein thrombosis (PVT). Thirty-seven of these patients had had prior major operative therapy. In only three patients (8%) was shunt surgery successful, and there was a high incidence of rebleeding, other morbidity, and mortality. Of especial note are the serious consequences of simple splenectomy; splenomegaly and thrombycytopenia should rarely, if ever, be used as indication for splenectomy in portal hypertension. In 1977, the use of selective distal splenorenal shunt (DSRS) was begun at Emory in this population and a selective shunt has been possible in 24 of 29 patients (83%) who had had no prior operative therapy. Results have been excellent with a greater than 90% patency rate, long-term portal perfusion in all, no encephalopathy, and late rebleeding in one patient. Quantitative studies at 3-6 years show stability of liver function, significant decrease in spleen size, and rise in platelet count. However, long-term follow-up (greater than 15 years) is required in PVT patients before definitive assessment can be obtained. A specific problem of the PVT patient is late shunt stenosis which requires close observation; dilatation of the shunt was performed in six of the 24 patients with a patent shunt. Poor results with non-shunt operative procedures in PVT were again documented. The proper role of endoscopic variceal sclerotherapy is not yet clear, but appears to be an excellent addition to the therapeutic options. In conclusion, for patients with a patent splenic vein, initial therapy should be a selective shunt; for patients without a patent splenic venous system, endoscopic sclerotherapy is the procedure of choice.

Adult↗
PubMed1988

Plasma concentrations of immunoreactive atrial natriuretic peptide in hospitalized cirrhotic and noncirrhotic patients: evidence for a role of deficient atrial natriuretic peptide in pathogenesis of cirrhotic ascites.

Atrial natriuretic peptide(s) (ANP), are thought to be released from the cardiac atria in response to distension. If decreased effective circulating blood volume is important in pathogenesis of ascites, plasma ANP levels would be expected to be decreased in ascitic subjects because of decreased atrial distension. To test this hypothesis, we measured plasma ANP by competitive radioimmunoassay in three groups of fasted, supine hospitalized subjects: nine noncirrhotic control subjects, 12 cirrhotics without ascites, and 17 cirrhotics with moderate to marked ascites. Immunoreactive plasma ANP concentrations were 195 +/- 41, 171 +/- 31, and 137 +/- 34 pg/ml (m +/- SD), respectively, in the three groups. The mean concentration in the group with cirrhosis and ascites was significantly (p less than or equal to 0.01) les than those of the other two groups, which did not differ from one another. These results support the concept that decreased effective circulating volume plays a role in pathogenesis of cirrhotic ascites, and that a relative deficiency of ANP plays a role in the sodium retention of decompensated cirrhosis.

Adult↗
PubMed1987

Leukoerythroblastosis with blasts in a patient with alcoholic hepatitis.

Leukemoid reactions are common in alcoholic hepatitis. We report a case of biopsy-proven alcoholic hepatitis with leukoerythroblastosis and blasts on the peripheral smear. We take this to be the second case of blasts and the first case of leukoerythroblastosis reported in a patient with alcoholic hepatitis.

Adult↗
PubMed1986

Distal splenorenal shunt versus endoscopic sclerotherapy for long-term management of variceal bleeding. Preliminary report of a prospective, randomized trial.

This paper reports the preliminary results of a prospective randomized trial comparing endoscopic variceal sclerosis and distal splenorenal shunt (DSRS) in the management of patients with cirrhosis and variceal bleeding. Seventy-one patients have been entered; 36 have received sclerosis and 35 DSRS. Randomization of the study population was stratified on Child's A/B (56%) and Child's C (44%). Sixty-one per cent had alcoholic and 39% non-alcoholic cirrhosis. No patients have been lost to follow-up, which currently stands at a median of 26 months. Rebleeding occurred significantly (p less than 0.05) more frequently in patients in the sclerosis group (19 of 36: 53%) compared to DSRS (1 of 35: 3%), but only 11 of 36 (31%) were not controlled by further sclerosis and failed that therapy. Patients in whom sclerosis failed underwent surgery. Survival was significantly (p less than 0.01) improved in the sclerosis group (+ surgery in 31%), with an 84% 2-year survival compared to a 59% 2-year survival in the DSRS group. Portal perfusion was significantly (p less than 0.05) better maintained in the sclerosis (95%) compared to the DSRS (53%) group. Galactose elimination capacity improved significantly (p less than 0.05) in 21 patients successfully managed by sclerosis at 1 year and was significantly (p less than 0.01) better maintained in the sclerosis compared to DSRS group. The authors conclude that endoscopic sclerosis: has a higher rebleeding rate than DSRS, with one third of patients failing therapy from rebleeding; allows significant improvement in liver function when successful; and gives significantly improved survival in the management of variceal bleeding when backed up by surgical therapy for patients with uncontrolled rebleeding.

Acute Disease↗
PubMed1985

Approach to the spectrum of Budd-Chiari syndrome: which patients require portal decompression?

Budd-Chiari syndrome (occlusion of the hepatic veins) represents a spectrum disorder. From 1974 to 1984, 20 patients with the syndrome were managed. Eleven required shunt surgery (Group 1) and 5 were managed with nonshunt therapy (Groups 2 and 3). Results have been good. Retrospective review of the liver biopsy specimens showed that Group 1 patients had a greater degree of zone 3 necrosis than Group 2 and 3 patients. We submit that presence of zone 3 necrosis on an initial liver biopsy specimen may define the failing liver of Budd-Chiari syndrome that requires conversion of the portal vein to an outflow tract by shunting.

Adult↗
PubMed1985

The Emory prospective randomized trial: selective versus nonselective shunt to control variceal bleeding. Ten year follow-up.

From 1971 to 1975, 55 patients with variceal bleeding secondary to cirrhosis were entered into a prospective randomized trial comparing distal splenorenal (selective) and H-graft interposition (nonselective) shunt. This 10-year follow-up documents that selective shunt is better (p less than 0.05) in four of the five variables monitored. Control of bleeding: selective shunt prevented variceal bleeding better than interposition shunt due to the higher (0.05 less than p less than 0.1) occlusion rate (30%) of interposition shunt. Selective shunt maintained postoperative portal perfusion better (p less than 0.01) than patent interposition shunt. Seventy-five per cent of selective shunt survivors have portal perfusion at 10 years: no patient with a patent nonselective shunt perfuses the liver. Quantitative liver function was better preserved (p less than 0.01) 10 years after selective shunt than nonselective shunt. Postoperative encephalopathy occurred in fewer (p less than 0.01) selective (27%) than nonselective (75%) shunt patients over the 10 years. Survival: in the randomized population, the improved survival in the selective shunt subgroup did not reach statistical significance. However, improved survival was confirmed in nonalcoholics. Five of eight nonalcoholics operated with selective shunt are alive at 10 years with patent shunts. No nonalcoholic, of seven total, operated with nonselective shunt survived 10 years with a patent shunt. These data show that selective shunt was superior to nonselective shunt. There was less rebleeding and encephalopathy after distal splenorenal shunt; postoperative portal perfusion and hepatic function were maintained.

Clinical Trials as Topic↗