I: the effects of recombinant human insulin-like growth factor-1 on nutritional recovery in the malnourished alcoholic rat.

BACKGROUND/AIMS: Alcoholics with severe liver disease (ALD) typically demonstrate the findings of protein calorie malnutrition. Such an occurrence might be anticipated with insulin-like growth factor-1 (IGF-1) deficiency. Furthermore, serum levels of IGF-1 are frequently very low in patients with alcoholic liver disease. The present study was undertaken to evaluate in an in vivo rat model of alcoholism and malnutrition, the possibility of a therapeutic application for IGF-1. METHODS: Controlled injury was induced by 14 days of calorie restriction and alcohol feeding (phase 1), which induced a 9% loss of body mass. Changes were compared with pair-fed, calorie-restricted controls that lost 7.8% of body mass and to unrestricted control rats that gained 28% above their pretreatment body mass during the same period. Recovery was evaluated after 28 days of treatment using various combinations of: (1) high calorie intake, (2) cessation from alcohol feeding, and (3) IGF-1. RESULTS: Liver injury was minimal, but protein calorie malnutrition was moderately severe after phase 1 treatments. During recovery (phase 2), continuous consumption of alcohol--even in the presence of high calories and IGF-1 treatment--produced an incomplete nutritional recovery and, compared with normal rats, was associated with lower serum IGF-1 levels. The group treated with all three modalities (high calories, IGF-1, and abstinence from ethanol) had the most rapid and complete restoration of body weight. CONCLUSIONS: Recovery of nutritional status in the malnourished rat correlates significantly with serum IGF-1 levels. In the absence of ethanol and with sufficient caloric intake, IGF-1 treatment increased serum IGF-1 concentrations and accelerated nutritional recovery. Even with adequate calories, ethanol negated this recovery and was associated with lower serum IGF-1 concentrations. Further studies, both basic and clinical, are needed to better understand the mechanisms involved and to establish whether in patients with severe liver disease IGF-1 treatment would produce an accelerated improvement in nutritional status and improve both morbity and mortality. These animal studies suggest that this is the case.

A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study.

A Veterans Affairs cooperative study involving 273 male patients was performed to evaluate efficacy of oxandrolone in combination with an enteral food supplement in severe alcoholic hepatitis. All patients had some degree of protein calorie malnutrition. On an intention-to-treat basis, only minimal changes in mortality were observed. However, in patients with moderate malnutrition mortality on active treatment at 1 mo was 9.4% compared with 20.9% in patients receiving placebo. This beneficial effect was maintained so that after 6 mo on active treatment 79.7% of patients were still alive, compared with 62.7% of placebo-treated patients (p = 0.037). Improvements in both the severity of the liver injury (p = 0.03) and malnutrition (p = 0.05) also occurred. No significant improvement was observed with severe malnutrition. To better determine the effect on therapeutic efficacy, we compared results with those from a nearly identical population (cooperative study 119) treated with oxandrolone but not given the food supplement. Patients were stratified according to their caloric intake (greater than 2,500 kcal/day was considered adequate to supply energy needs and promote anabolism). For patients with moderate malnutrition and adequate caloric intake, oxandrolone treatment reduced 6-mo mortality (4% active treatment vs. 28% placebo [p = 0.002]). For patients with moderate malnutrition and inadequate calorie intake, oxandrolone had no effect on mortality (30% active treatment vs. 33% placebo). In cases of severe malnutrition, oxandrolone had no effect on survival. However, adequate caloric intake was associated with 19% mortality, whereas patients with inadequate intake exhibited 51% mortality (p = 0.0001). These results indicate that nutritional status should be evaluated in patients with alcoholic hepatitis. When malnutrition is present, vigorous nutrition therapy should be provided, and in patients with moderate malnutrition oxandrolone should be added to the regimen.

Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid.

Forty-three hospitalized patients were treated with a new antibiotic combination containing ticarcillin plus the beta-lactamase inhibitor, clavulanic acid, in a fixed combination for intravenous use. A variety of infections were treated, including pneumonia, bacteremia, urinary tract infection, and osteomyelitis. Of 50 episodes of infection in 43 patients, 44 clinical cures were obtained, with 5 patients improving and 1 patient failing to respond to treatment. In vitro susceptibility testing of 101 clinical isolates was notable for the rarity of resistance to the combination antibiotic. Of specific interest, all 14 isolates of Staphylococcus aureus were susceptible to ticarcillin plus clavulanic acid, whereas only 2 of the 14 isolates were susceptible to ticarcillin alone. Adverse reactions to the study drug were minimal; eosinophilia, unaccompanied by other allergic phenomena, and oral candidiasis were most frequent. Overall, the combination of ticarcillin with the beta-lactamase inhibitor, clavulanic acid, appears to be a safe and effective drug for the treatment of infections caused by susceptible organisms.