Clinical and economic outcomes of individuals with severe peptic ulcer hemorrhage and nonbleeding visible vessel: an analysis of two prospective clinical trials.

OBJECTIVE: We report the clinical outcomes and direct medical costs of 155 patients with severe peptic ulcer hemorrhage and a nonbleeding visible vessel at emergency endoscopy treated with endoscopic hemostasis or medical-surgical therapy. METHODS: In two consecutive, prospective, randomized, controlled trials, patients were randomly assigned to endoscopic hemostasis (heater probe, bipolar electrocoagulation, or injection sclerosis) or medical-surgical treatment. Study endpoints included the incidence of severe ulcer rebleeding and emergency surgery, length of hospital stay, blood transfusion requirements, mortality rate, and direct costs of utilized health care. Direct medical costs were estimated using combined fixed and variable institutional costs for consumed resources and Medicare reimbursement rates. RESULTS: Compared with medical-surgical treatment, endoscopically treated patients had significantly lower rates of severe ulcer rebleeding (p = 0.004), emergency surgery (p = 0.002 and p = 0.019, 0.024), and blood transfusions (p = 0.025). Observed inter-trial differences in ulcer rebleeding rates may be partially explained in a multivariate model by covariates of comorbid disease and inpatient ulcer bleeding. In both trials, length of hospital stay, mortality rates, and treatment-related complications were similar. Estimated median direct costs per patient differed: The first trial had lower costs with endoscopic hemostasis ($4254, vs $4620 for electrocoagulation and $5909 for medical-surgical treatment), yet the second trial yielded lower costs with medical-surgical treatment ($3169, vs $3477 for injection sclerosis and $4098 for heater probe). CONCLUSIONS: Compared with medical-surgical therapy, endoscopic hemostasis for severe ulcer hemorrhage and a nonbleeding visible vessel yielded significantly better patient outcomes and was safe. This procedure may or may not yield lower direct medical costs and cost savings.

Severe upper gastrointestinal tumor bleeding: endoscopic findings, treatment, and outcome.

BACKGROUND AND STUDY AIMS: The aim of the present study was to review endoscopic findings, treatment, and clinical outcomes in patients with severe upper gastrointestinal bleeding due to tumors. PATIENTS AND METHODS: A retrospective analysis was made of prospectively gathered data on all patients with severe upper gastrointestinal bleeding who were admitted to two large referral centers during a 45-month period. RESULTS: Nine hundred thirty-five patients had severe upper gastrointestinal bleeding, of whom 42 (5%) were found to have tumors. Histologically, nearly all of the tumors were of a malignant type. Fifty-two percent of the patients had acute severe upper gastrointestinal bleeding as the initial presentation of their tumor. The most common tumor was gastric adenocarcinoma, and all of these cases were at advanced stages. Endoscopic hemostasis with thermal probes or epinephrine injection, or both, was carried out in seven patients (17%), with successful hemostasis in all of the tumors. Regardless of the treatment given, patients with upper gastrointestinal tumor bleeding, had a 30-day surgery rate of 43%, a 30-day rebleed rate of 33%, a 30-day mortality rate of 10%, and a 1-year mortality rate of 89%. CONCLUSIONS: Most tumors that cause severe upper gastrointestinal bleeding are of a malignant histologic type and are already at an advanced stage. Endoscopic hemostasis of bleeding upper gastrointestinal tumors is safe and initially effective, and may provide time for elective surgical palliation. Regardless of therapy, upper gastrointestinal tumors with severe bleeding have a poor one-year survival.

Chloroethylene mixtures: pharmacokinetic modeling and in vitro metabolism of vinyl chloride, trichloroethylene, and trans-1,2-dichloroethylene in rat.

Environmental and occupational exposures are typically to mixtures of chemicals, although most toxicity information is for individual compounds. Interactions between chemicals may involve pharmacokinetic and/or pharmacodynamic effects resulting in modulation of toxicity. Therefore, physiologically based pharmacokinetic modeling has been used to analyze data describing the metabolism of vinyl chloride (VC) and trichloroethylene (TCE) mixtures in rats. A single saturable pathway was modeled, representing cytochrome P450 2E1. This was partially validated using preexposure to trans-1,2-dichloroethylene (tDCE) which virtually eliminated in vivo metabolism of both VC and TCE at low concentrations. Microsomes from tDCE-exposed animals showed inhibition of metabolism of P450 2E1 substrates (chlorzoxazone, p-nitrophenol, and TCE) and no effect on 7-ethoxycoumarin deethylation. Studies with liver microsomes from VC-exposed animals found that neither suicide inhibition nor induction occurred during 6-hr exposures to high concentrations. Therefore, these effects were not modeled. Modeling of mixtures of VC and TCE was successful only using competitive inhibition, as might be predicted for cytochrome P450 2E1 substrates, and not uncompetitive or noncompetitive inhibition. These results were further confirmed by determining the depletion of glutathione due to VC metabolism. The validation of a detailed model for the inhibition kinetics of metabolism of these two compounds permits better understanding of the implications of coexposures for toxicity. It is notable that competitive inhibition only becomes significant at relatively high concentrations (tens of ppm), while at typical low environmental concentrations (ppb), absorption is perfusion limited and enzyme is in excess so that the chemicals will be metabolized independently.

Prospective randomized comparative study of bipolar versus direct current electrocoagulation for treatment of bleeding internal hemorrhoids.

Internal hemorrhoids are the most common cause of lower gastrointestinal bleeding. Although new anoscopic therapies are available, few comparative randomized studies have evaluated them in regard to long-term efficacy, recurrence rates, and safety. Our purpose was to compare the treatment of internal hemorrhoids with direct current (Ultroid, Cabot Medical, Langhorn, Pa.) and bipolar (BICAP, Circon ACMI, Stamford, Conn.) hemorrhoid probes. One hundred patients with symptomatic internal hemorrhoids were randomized: 50 to direct current electrocoagulation and 50 to bipolar electrocoagulation. Follow-up and treatment were at 3- to 4-weekly intervals; two to three hemorrhoid segments were treated at each session until relief of symptoms (bleeding, prolapse, and discharge) and a reduction in hemorrhoid size to grade 1 or 0 were noted. The hemorrhoids of 98% of all patients studied were grade 2 or 3; 2% of patients had grade 1 hemorrhoids and none had grade 4 hemorrhoids. At 1 year after treatment, most patients had no (69%) or only mild (23%) recurrence, and a few had severe, symptomatic (8%) hemorrhoid recurrence. A greater recurrence rate was noted after direct current treatment (34%) than bipolar treatment (29%). In contrast, rebleeding at 1 year occurred less frequently after direct current treatment (5%) than after bipolar treatment (20%). Our conclusions were as follows: (1) Both direct current and bipolar probes were effective for control of chronic bleeding from grade 1 to 3 internal hemorrhoids. (2) Bipolar probe was significantly faster than direct current probe. (3) Direct current treatment produced fewer complications than bipolar treatment (12% versus 14%). (4) Recurrence rates were low after 1 year with either device (8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Computer simulation of the lactational transfer of tetrachloroethylene in rats using a physiologically based model.

A physiologically based pharmacokinetic (PBPK) model describing transfer of inhaled tetrachloroethylene (PCE) into breast milk with the consequent exposure of the nursing pups was developed and validated in lactating rats. The PBPK model was based on partition coefficients (PCs), which were determined by the equilibration of tissues with known concentrations of PCE vapor. The blood/air and milk/blood PCs for the dam were 33.5 and 12.0, the liver/blood and fat/blood PCs for the dam were 1.9 and 42.4, and the slowly perfused tissues/blood and rapidly perfused tissues/blood PCs for the dam were 0.9 and 1.7, respectively. The blood/air PC for the pup was 24.3, and the solid tissues/blood PC for the pup was 4.5. Metabolic constants were determined by a gas uptake method. The pseudo-maximal velocity of PCE metabolism in the dam was low, 0.03 mg/kg/hr, and the apparent Michaelis-Menten constant was 0.3 mg/liter. The lactating Sprague-Dawley females were exposed to PCE vapor for 2 hr with concentrations ranging from 20 to 1000 ppm PCE. The dams were returned to the pups after exposure and the pups received PCE via breast milk while they nursed. PCE concentrations in the air, blood, milk, and tissues were determined by gas chromatography and compared to PBPK model predictions. Nursing resulted in a peak pup blood PCE concentration of 0.9 mg/liter and a peak pup solid tissue PCE concentration of 8 mg/kg. The PBPK lactation model adequately described the distribution of inhaled PCE in maternal blood and milk, as well as in the nursed pup's gastrointestinal tract, blood, and solid tissues. It is concluded that the predictions based on PBPK modeling for disposition of PCE in lactating rats and their pups were in good agreement with the experimental data.

Controlled study of different sclerosing agents for coagulation of canine gut arteries.

Excellent clinical results have been reported with sclerotherapy for control of nonvariceal gastrointestinal hemorrhage. However, there are few controlled or comparative data on different sclerosing agents for treatment of lesions with active arterial bleeding or nonbleeding visible vessels. In a controlled, randomized study of canine small bowel arteries our purposes were (a) to evaluate the efficacy for arterial coagulation of six sclerosing agents compared with normal saline control, (b) to compare the resultant tissue injury of agents, and (c) to elucidate the possible mechanisms of arterial coagulation and tissue injury of the agents. The agents evaluated were (a) 98% ethanol, (b) TES, a mixture with final concentration of 1% tetradecyl sulfate, 32% ethanol, and 0.3 normal saline, (c) 1% polidocanol (Ethoxysclerol), (d) 1:10,000 epinephrine, (e) 7.2% hypertonic saline, (f) 3.6% hypertonic saline, and (g) 0.9% saline (normal saline control). Agents were injected from the mucosal side of the small bowel into and around the pentrating serosal arteries in the subserosal space. Ethanol and TES were the most effective agents for arterial coagulation. Polidocanol was less effective than ethanol and TES. However, it was the only other agent that induced significant arterial coagulation. Alcohol and TES also caused significant injury in surrounding tissue. The degree of this injury was dependent on the total volume injected. Epinephrine induced significant mucosal damage without significant serosal injury or arterial coagulation. The coagulation and tissue injury effects of hypertonic saline injections were not significantly different from normal saline control.

The effect of exercise on the toxicity of aflatoxin B1 in chickens.

Three trials were conducted to study the effects of exercise on aflatoxicosis in young broiler and layer chicks. Aflatoxin B1 was fed at levels of 0 or 5 ppm in a corn-based diet. Exercise was conducted on a motorized treadmill. In one trial, the growth rate of aflatoxin-fed birds was found to be increased significantly (P less than .05) by exercise, but it was not equal to that of the control birds. In other trials, growth rates were increased by exercise in birds receiving aflatoxin, but not significantly. Feed consumption measurements indicated that the decreased growth rates in the aflatoxin-fed birds were due to decreased feed consumption. Glucose-6-phosphate dehydrogenase levels were decreased significantly in the unexercised broiler chicks fed aflatoxin (P less than .025). In one trial, liver weights of broiler chicks were increased significantly by aflatoxin (P less than .005). In the birds fed aflatoxin and exercised, liver weights also were increased but to a lesser degree (P less than .01).