Use of omeprazole in the management of giant duodenal ulcer: results of a prospective study.

BACKGROUND: Giant duodenal ulcer (GDU) is generally thought to require surgical intervention. Proton pump inhibitors have beneficial effects in peptic ulcer disease, but their role in GDU disease is unknown. We examined the use of omeprazole in GDU management. METHODS: Twenty-eight patients were diagnosed with GDU. One patient required immediate operative intervention. The remaining 27 were placed on omeprazole (40 mg daily). When ulcer healing was documented by endoscopy, the patients were placed on oral histamine-2 receptor antagonist therapy. RESULTS: Of the 28 study patients, 20 (71.4%) did not require operative intervention, and 8 (28.6%) required operation for ulcer complications. Of the 15 patients with adherent clot or a visible vessel at initial endoscopy, 7 (46.7%) required operative intervention, as compared with 1 (7.7%) of the 13 patients without a visible vessel or adherent clot. This difference was statistically significant (P < .05). Twenty-three patients underwent antral biopsy and/or enzyme-linked immunosorbent assay for Helicobacter pylori, and 9 (39.1%) had a positive result. CONCLUSIONS: Omeprazole is effective in the treatment of GDU disease. An adherent clot or a visible vessel at endoscopy indicates a higher likelihood of complications requiring operation. The relatively low H pylori infection rate, as compared with other peptic ulcer disease, may indicate a different pathophysiology in GDU.

Does use of the Coloscreen Self-Test improve patient compliance with fecal occult blood screening?

Occult blood-screening methods which do not require stool manipulation have been devised in an attempt to improve patient compliance with fecal occult blood testing. We performed a randomized, prospective study comparing patient compliance with the Coloscreen Self Test, a fecal occult blood detection method which does not require stool manipulation, and standard guaiac-impregnated cards in a VA clinic and a university-based private practice to determine whether the Coloscreen Self-Test would improve patient compliance with fecal occult blood testing. Overall, there was no significant difference in compliance between the two tests, with a compliance of 71% (105/147) for the guaiac cards and 60% (88/136) for the Coloscreen Self-Test (p = 0.49). However, multiple logistic regression showed that, when using the Coloscreen Self-Test, patients at the VA clinic had significantly reduced compliance. Only 46% (23/50) returned the Coloscreen Self-Test compared with 84% (42/50) who returned the guaiac cards (p < 0.05). We conclude that the Coloscreen Self-Test does not improve patient compliance with fecal occult blood testing, and may reduce compliance in some sectors of the population.

Biochemical and clinical effects of aspartame in patients with chronic, stable alcoholic liver disease.

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.

Alpha-fetoprotein alterations in alcoholics with liver disease. V.A. Cooperative Study Groups.

Sera on 409 male alcoholics with liver injury were assayed for alpha-fetoprotein (AFP) as part of a VA co-operative study on the natural history and therapy of alcoholic liver disease. In 78% of the patients values below normal were observed and 42% had undetectable levels. Clinically the lowest AFP concentrations were observed in the more severely ill patients with the poorest 1 year survival. Furthermore, improvement in AFP was associated with improved survival. Correlation analysis showed a relationship of AFP to (1) visceral protein concentrations (i.e. albumin, transferrin, retinal binding protein); (2) variables related to hepatic fibrogenesis (i.e. Ito cell activity, quantitative estimates of fibrosis and Kupffer cell abnormalities); and (3) changes in immunoglobulin levels particularly IgG. These findings suggest that AFP is a good index of disease prognosis.

Misdiagnosis of the Zollinger-Ellison syndrome due to hyperlipidemia.

Most authorities feel that diagnosis of the Zollinger-Ellison syndrome is established when the serum gastrin level is greater than 1000 pg/mL (1000 ng/L) in a patient with gastric acid hypersecretion and clinical manifestations consistent with the diagnosis. A patient with recurrent peptic ulcer disease is reported who was thought to have had the Zollinger-Ellison syndrome based on two serum gastrin level measurements greater than 1000 pg/mL (1000 ng/L). Subsequent evaluation revealed the gastrin elevation to be spurious because the sample was hyperlipidemic. Lipemic serum samples may yield falsely elevated serum gastrin determinations as determined by radioimmunoassay.

Longevity among ethnic groups in alcoholic liver disease.

As part of a multicenter V.A. Cooperative Study, 437 male veterans with varying stages of alcoholic liver injury were followed over a 4.5 year period. Their ethnic distribution consisted of 256 Caucasians, 109 black Afro-Americans, 63 Puerto Rican Hispanics, and 9 Native American Indians. Survival analyses revealed significant differences between groups (P = 0.0002): 66% of Afro-Americans were still living at 42 months; Caucasians were intermediate with 40% survival; and only 28% of Hispanics were alive. The number of Native American Indians enrolled was too small to draw conclusions but none of those enrolled survived beyond 24 months. Survival regression analysis of 30 clinical, laboratory, histologic and nutritional parameters, revealed the following significant risk factors: clinical severity (P less than 0.0001), histologic severity (P less than 0.0001), race (P = 0.001), age (P = 0.002), BUN (P = 0.01) and ALT (P = 0.02). These analyses indicated that ethnicity, independent of other variables, is significantly associated with outcome from the disease.

Effect of Strongyloides ratti on small bowel function in normal and immunosuppressed host rats.

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.

Lymphocyte subset alterations in patients with alcoholic hepatitis.

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.

Hepatitis B vaccination. Response of alcoholic with and without liver injury.

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 greater than 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 less than 0.05, group I vs III). In those who did not respond, a significant (P less than 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.

Strongyloidiasis in US veterans of the Vietnam and other wars.

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.

Escherichia coli peritonitis after left-sided colonoscopy in a patient on continuous ambulatory peritoneal dialysis.

A 69-yr-old man on chronic ambulatory peritoneal dialysis presented with Escherichia coli peritonitis 36 h after left-sided colonoscopy. No evidence for colonic perforation was found and the infection cleared with intravenous and intraperitoneal antibiotics. This case supports the need for further studies evaluating the use of prophylactic antibiotics during colonoscopy of chronic ambulatory peritoneal dialysis patients with diverticula.

VA Cooperative Study on Alcoholic Hepatitis. IV. The significance of clinically mild alcoholic hepatitis--describing the population with minimal hyperbilirubinemia.

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.

Improved survival in squamous esophageal cancer. Preoperative chemotherapy and irradiation.

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.

A new therapy for portal systemic encephalopathy.

This report describes a new therapeutic approach to the treatment of adults with portal systemic encephalopathy using sodium benzoate and sodium phenylacetate, two compounds that increase conjugated nitrogen excretion in the urine and that have been shown to be an effective treatment for children with congenital hyperammonemia. The study was a double-blind cross-over study in which each patient was his own control. All patients either improved their mental status (six of eight) or maintained a mental status comparable to that achieved with conventional therapy [lactulose or neomycin (two of eight)]. All decreased their blood ammonias on these medications and seven of eight improved their portal systemic encephalopathy index. It is suggested that these medications may be useful in the treatment of portal systemic encephalopathy.

Congenital hepatic fibrosis and cerebral aneurysm in a 32-year-old woman.

Congenital hepatic fibrosis has been associated with a number of visceral abnormalities, but only rarely with cerebral aneurysms. We report a case of a 32-year-old woman with congenital hepatic fibrosis and a subarachnoid hemorrhage secondary to a ruptured cerebral aneurysm. A review of the literature reveals only two previous reports of such an association and both were also associated with polycystic kidney disease. Our patient is unique in that she does not have polycystic kidney disease but rather medullary sponge kidney.

VA cooperative study on alcoholic hepatitis. II: Prognostic significance of protein-calorie malnutrition.

Three hundred and fifty-two patients with alcoholic hepatitis were evaluated for protein-calorie malnutrition (PCM). In order to facilitate data analysis of nutritional status, a PCM score was calculated for each patient using eight nutritional parameters. The PCM score correlated significantly with mortality, clinical severity of the liver disease, and biochemical liver dysfunction. When 30 day changes in the PCM scores were compared with 30 day caloric intake (expressed as percent basal energy expenditure (BEE], a marginally significant correlation was observed (p = 0.05). However, those patients who showed improvement in their PCM score over 30 days of hospitalization also improved their 6-mo and 1-yr survival. These data indicate that nutrition, as determined by the PCM score, has prognostic significance. Additional studies are needed to establish the beneficial role for vigorous protein-calorie nutritional therapy in the management of alcoholic hepatitis.

VA Cooperative Study on Alcoholic Hepatitis. III: Changes in protein-calorie malnutrition associated with 30 days of hospitalization with and without enteral nutritional therapy.

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.

Effect of chronic ethanol consumption on the pancreas of the hamster.

The purpose of this study was to determine the effect of chronic ethanol consumption on pancreatic morphology and biochemistry in the hamster, with special attention to lipid changes. A control group of Syrian golden hamsters fed a synthetic liquid diet was compared to an ethanol group pair-fed the same diet with ethanol substituted for 35% of the carbohydrate calories. The animals were sacrificed at 7 weeks and 3, 6, 9, and 12 months. After 12 months of ethanol consumption, a significant decrease in pancreatic triglycerides and a significant increase in pancreatic RNA was seen. These changes were associated with a rise in pancreatic weight and protein content in the ethanol group, reversing a six-month decline in these values. This rise in RNA and protein in the ethanol-treated group corresponded with the appearance of large abnormal zymogen granules. Other ultrastructural features such as lipid droplets, mitochondria, and endoplasmic reticulum were not altered by ethanol. Ethanol did increase the water content of the pancreas. Although ethanol had no effect on the fasting levels of insulin or pancreatic polypeptide, the fasting serum gastrin immunoreactivity was significantly lower in the ethanol animals. This study shows that chronic ethanol consumption produces a metabolic change in the hamster by 12 months which is suggestive of increased protein synthesis with a decrease in pancreatic triglycerides and no lipid droplet formation.