Aspartame is an artificial sweetener completely metabolized in the gut and absorbed as aspartate, phenylalanine, and methanol. Phenylalanine is thought to mediate or exacerbate hepatic encephalopathy, and an impaired liver may not be able to cope with the ammoniagenic properties of the amino acid constituents, or adequately metabolize methanol. Thus, we compared the clinical and biochemical effects of a single ingestion of aspartame (15 mg/kg) to skim milk (phenylalanine content equimolar to aspartame) and placebo in patients with chronic, alcoholic liver disease in a randomized, crossover study. Aspartame produced an elevation of plasma phenylalanine significantly greater than milk and placebo (Cmax 14.55 +/- 7.38, 10.95 +/- 4.95, 8.84 +/- 4.55 mumol/dl, respectively; p < 0.01). However, quantified encephalopathic changes were observed only with milk (p < 0.05). Plasma aspartate, methanol, formate, and ammonia levels remained unchanged after all treatments. The lack of clinical derangements in encephalopathic indices, methanol accumulation, or biochemical changes in liver status suggests that a single large dose of aspartame (representing 5 times the average daily intake of adults) may be used safely by patients with chronic, stable liver disease.

Justified When the Stool Hemoccult is Positive but the Colonoscopy is Negative?____~___ Acid Secretion in Human Immunodeficiency Virus Infection My Grandmother's Intravenous Chicken Soup Should We Transplant Hepatitis C-Positive Organs?_-__ __.

Twenty-three patients with alcoholic hepatitis (AH) were entered into a study to evaluate the relationship between alcoholic hepatitis, malnutrition, and immune status. In order to quantify these variables, objective parameters of nutritional status and lymphocyte phenotype and function were used. On admission to hospital, the mean number of CD4 helper/inducer cells, CD8 suppressor/cytotoxic cells, and CD3 lymphocytes were significantly reduced compared to age matched, non-hospitalized laboratory controls. In order to ascertain whether this abnormality was reversible, 12 patients, who were willing to remain in the hospital for 30 days, were treated for this entire period with oral nutritional supplementation using a commercially available preparation high in calories, protein, and branch chain amino acids. After 30 days of this therapy and abstinence, the number of CD4 cells increased from a mean (+/- SD) of 658 +/- 428 to 815 +/- 599/mm3. There was no difference in results of the lymphocyte transformation test comparing pre- and post-therapy values using either fetal calf or autologous serum. For all groups tested, cells cultured in autologous serum exhibited a significantly decreased response to mitogen compared to cells cultured in fetal calf serum. Both the total nutritional and the protein depletion (kwashiorkor) scores improved significantly during the 30 days of nutritional supplementation (p less than 0.0009 and p less than 0.0004, respectively). Therefore, we have observed an alteration in the numbers of helper lymphocytes in patients admitted with AH. This abnormality was modifiable by abstinence and nutritional supplementation over a brief period of hospitalization.

Alcoholics are at risk to develop hepatitis B infections, chronic active hepatitis, and even hepatoma. Hence, immunization with hepatitis B vaccine is recommended. However, immune abnormalities may coexist which alter their responsiveness to vaccination. This study compares the immune response to this vaccine in controls (group I), alcoholics without overt liver disease (group II), and alcoholics with clinical liver disease (group III). By the seventh month after the initial vaccination, 89% in group I, 70% in group II, and 18% in group III had a response >36 RIA units. The magnitude of the response was significantly different in groups I, II, and III (19,456 vs 8,326 vs 153 RIA units, respectively; P <0.05, group I vs III). In those who did not respond, a significant (P < 0.02) lower helper/inducer (T4)class of lymphocytes was observed as compared to patients who exhibited an adequate response. These observations suggest: (1) that the response to hepatitis B vaccine is a T-cell-dependent event and (2) that in this population, using the existing vaccine, postvaccination evaluations of antibody concentrations are needed before protection against hepatitis B infection can be assumed.

Although Strongyloides stercoralis is a common parasite, little is known about its effect on intestinal function. Published clinical studies are difficult to evaluate and compare because of the inability to differentiate the effects of the parasite load from that of various other coexisting features such as bacterial overgrowth, multiparasitism, malnutrition, or tropical sprue. Using a rat model where these problems do not occur, we found that Strongyloides ratti did not inhibit intestinal function in the healthy rat. In fact, in normal rats S. ratti appeared to increase ileal sucrase activity. In contrast, in the methylprednisolone-treated rat, S. ratti produced a decrease in lactase and sucrase activity and an increase in alkaline phosphatase activity. S. ratti had no effect on 3-O-methylglucose uptake or D-xylose absorption in either group. These results suggest that S. ratti has little effect on small bowel function in a healthy rat but can cause minor alterations in intestinal function in an immunosuppressed, methylprednisolone-treated, malnourished host. These results are also consistent with clinical observations seen with S. stercoralis in humans and with another nematode, Ascaris suus, in the pig model.

The prevalence of strongyloidiasis among American veterans of the Vietnam and other wars was evaluated by testing several groups of veterans for serum IgG antibodies against Strongyloides stercoralis antigens, using an enzyme-linked immunosorbent assay. Of 493 Vietnam veterans, eight (1.6%) were seropositive. Of 60 patients with abdominal symptoms and/or elevated eosinophilia (greater than 0.08 [greater than 8%]) admitted to the Cincinnati Veterans Administration Medical Center, 12 (5%) were seropositive. Of 147 residents of a Veterans Administration-operated nursing home, six (4%) were seropositive. All infected patients in the latter two groups were World War II veterans. The usefulness of the enzyme-linked immunosorbent assay as a screening tool for at-risk groups is suggested by the finding that S stercoralis larvae were demonstrated in most seropositive patients when a sufficient number of fresh stools were examined.

Initial trials of irradiation and chemotherapy followed by operation for squamous carcinoma of the esophagus have produced encouraging results. Over the past three years, with palliative and curative intent, we have treated 27 unselected patients initially with two courses of chemotherapy (fluorouracil and either cisplatin, mitomycin, or cisplatin and vincristine sulfate) given 29 days apart and 3000 rad (30 Gy) of radiation. Ten patients have then undergone esophageal resection and two patients have undergone esophageal bypass. Results are compared with those of 70 unselected historical control patients treated since 1979. Survival at 30 months was significantly improved for multimodality-treated patients (21.4% +/- 10.1%, mean +/- SEM) when compared with historical control patients (4.8% +/- 2.7%). Twenty-four percent of multimodality-treated patients had complete remission of all tumor. These data indicate that overall therapy for carcinoma of the esophagus has been improved in our institutions.

As part of a large multicenter Veterans Administration Cooperative Study of Alcoholic Hepatitis, 89 patients with clinically mild biopsy-proven disease were followed for at least 30 months. Although clinical and laboratory abnormalities were minimal, cirrhosis was present in 38%, and mortality was 22% at 30 months. Clinical features suggesting more advanced disease (i.e., ascites and encephalopathy) and laboratory parameters for the diagnosis of alcoholic hepatitis and/or cirrhosis were imprecise and frequently misleading. The histologic diagnosis of cirrhosis correlated best with changes in immunoglobulin A, prothrombin time, and SGOT/SGPT. However, by using logistic discriminant analysis on 26 commonly available laboratory tests to diagnose cirrhosis, only a 72% sensitivity and 88% specificity could be obtained. Mortality in the patients with cirrhosis (10/34) was significantly higher at 1 and 2 yr compared with patients without cirrhosis (10/55, p less than 0.01). The high mortality in noncirrhotics may have resulted from progression to cirrhosis subsequent to the initial evaluation. Thus, liver biopsy in this population with minimal disease seems necessary to establish both an accurate diagnosis and the reversibility of the disease.

Patients with moderate to severe alcoholic hepatitis and features of protein-calorie malnutrition were studied with respect to changes in their nutritional status during 30 days of hospitalization. Thirty-four patients served as controls, were given a 2500 kcal hospital diet and allowed to eat ad libitum. Twenty-three patients were given, in addition to the hospital diet, a nutrition supplement high in calories, protein, and branched-chain amino acids (Hepatic Aid). Because of anorexia, the controls consumed lesser amounts of both calories and protein while those given the nutritional therapy exceeded their estimated energy requirements (116.1%) and consumed a mean of 98.3 g of protein per day. This was well tolerated despite the fact that portal systemic encephalopathy was present in 72% of the patients. Mortality associated with the liver disease was comparable in both groups, 16.7% in the treated vs 20.6% in the controls. In those patients that survived the 30 days of hospitalization, clinical and biochemical tests of liver injury improved in both groups. With respect to their nutritional status, those given nutritional therapy showed significant improvement in six of the nine parameters (67%) used to assess nutrition. In the controls significant improvement was observed in only two nutritional parameters (22%) while three parameters (33%) deteriorated further. These three were all associated with calorie deprivation (marasmus). This study suggests that patients with acute alcoholic hepatitis require additional nutritional therapy to maintain and improve their nutrition parameters, especially those related to marasmus; and that Hepatic Aid is well tolerated for this purpose.