t h a n 50% of the bowel lumen. Pathologic examination demonstrated the adenocarcinomatous nature of the mass. An abdominal ultrasonogram showed a well-delimited hypoechogenic image at the right hepatic lobule and a left renal cyst. The differential diagnosis between CGL and neutrophilic leukemoid reaction was initiated. The leukocyte count was more than 50 × 109/L, but no splenomegaly was observed. The neutrophilic alkaline phosphatase score was below normal. Serum cobalamin levels were v e r y high: 4,364 p m o l / L (5,915 p g / m L ) . B o n e m a r r o w smears showed granulocytic hyperplasia, and bilateral bone marrow core biopsy revealed no metastatic carcinoma. The Philadelphia chromosome was observed in all the metaphase bone marrow cells studied. Our patient underwent palliative surgical resection, and a sample from the hepatic lesion located in the right hepatic lobule, previously detected on the abdominal ultrasonogram, was taken. The pathologist's diagnosis was metastatic adenocarcinoma of the liver. We made the simultaneous diagnosis of Philadelphia chromosome-positive CGL and a metastatic adenocarcinoma giving rise to a neutrophilic leukemoid reaction. T h e medical i m p l i c a t i o n s of overlooking CGL in a patient with another neoplasm that has a worse vital prognosis (i.e., metastatic disease) might be negligible, but the error may have more serious consequences if the solid neoplasm is restricted to the bowel and the assumption is made that the peripheral blood picture is indicative of widespread disease. The coexistence of chronic myelogenous leukemia and other hematologic neoplasms has been communicated on several occasions [2-4], but the simultaneous diagnosis of Philadelphia chromosome-positive CGL and a solid neoplasm is exceptional [5]. H o w e v e r , t h i s p o s s i b i l i t y should be kept in mind since it may have implications for patient care. 15. J. RAMOS, F. ZAMORA, M. P~REZ-SICILIA, M. A. SANZ, R. dEL VILLAR,

M.D. M.D. M.D. M.D. M.D.

Hospital General "Rio Carri6n Palencia, Spain


1. Wintrobe MM: Variations of leukocytes in disease. Leukemoid blood pictures. In: Clinical hematology, 8th ed. Philadelphia: Lea & Febiger, 1981; 13121314. 2. Paolino W, Rossi M, Infelise V, Degani G, Levis A: L'associazione leucemie-tumori. Indagine su 502 casi di leucemia. Minerva Med 1976; 67: 1196-1203. 3. Lewis MJ, Oelbaum MH, Coleman M, Allen S: An association between chronic neutrophilic leukaemia and multiple myeloma with study of cobalamin binding proteins. Br J Haematol 1986; 63: 173-180. 4. Feiiu Batlle J, GarcTa de Predes JL, Garc~a GirSn C, Torres Nieto A, Ord6nez Gallego A, Gonzf~lez Bar6n M: Goexistencia de una leucemia mieloide cr6nica y un linfoma Ten una enferma. Rev Clin Esp 1987; 180: 155-157. 5. Carruth JE, Glasser SH, Levin J: Gastric carcinoma and other malignancies in patients with chronic myelogenous leukemia. Case report and review of the literature, with particular reference to young adults. Johns Hopkins Med J 1980; 147: 213-216. Submitted September 20, 1989, and accepted October 2, 1989


Entamoeba histoiytica is an enteric protozoan parasite that infects up to 10% of the world's population [1]. In 10% of infected individuals, this lumen-dwelling parasite can invade the intestinal mucosa, creating substantial tissue damage, or disseminate to soft organs, causing abscesses, most notably the liver. Overall, invasive amebiasis results in 100,000 deaths annually [1]. Data obtained from studies with humans as well as in animal models of amebiasis suggest that, following infection, protective immunity is elicited [2]. The role of cytokines in this acquisition of immunity or in immune-mediated pathology is not known. Recent studies from our laboratory have focused on the putative role of cytokines in activating macrophages and neutrophils for the in vitr(~ killing of amebas [3,4]. In this study, we evaluated the possibility that serum from patients with intestinal or liver amebiasis or serum from gerbils with e x p e r i m e n t a l l y induced amebic liver abscesses contained tumor necrosis factor (TNF), which would be expected to contribute to the immunopathology. T w e n t y - n i n e s e r u m samples from clinical cases of amebiasis were tested for the presence of TNF. Twenty of these sera came from patients with amebic liver ab-

January1990 The AmericanJournalof Medicine Volume88

scesses and nine from patients with amebic colitis. All patients subsequently recovered completely after specific antiamebic drug therapy. Sera from five healthy individuals served as negative controls. Gerbil sera were obtained from animals with amebic liver abscesses at 10, 20, and 30 days after infection. All sera from patients with amebiasis and from animals with amebic liver abscesses were strongly positive for the presence of antiamebic antibodies, as determined by enzymelinked i m m u n o a b s o r b e n t assay and Western blot test. Sera were tested for the presence of T N F by the use of bioassay with actinomycin-D-treated L929 murine fibroblasts and crystal violet [5]. This procedure can detect amounts of T N F as low as 5 pg/50 #L of fluid [6]. All sera tested negative for the presence of TNF, confirming other preliminary findings [6]. This suggests that despite the intense inflammatory reaction elicited by the parasite in acute amebiasis [7], an important component of the response, notably cytokine TNF, is not present in the serum of patients or animals with invasive amebiasis. Amebas in close contact with macrophages can down-regulate their functions, including interleukin-1 formation, Ia antigen expression, and hydrogen peroxide production [8]. Perhaps TNF-a, a neutrophil activator, is also altered in this interaction locally and may explain, in part, the intense neutrop h i l i c i n f i l t r a t e seen e a r l y in amebic liver abscess formation [7]. in parasite infections, high levels of serum T N F are seen in patients with visceral leishmaniasis and malaria, whereas a variety of neoplastic disease conditions elicit a low T N F response [6]. These results suggest that T N F levels are not present in the systemic circulation in acute invasive amebiasis, probably because of the localized nature of the abscesses. It would be interesting to determine whether the abscess material contained TNF. MICHEL DENIS KATHY KELLER KRIS CHADEE Institute o/Parasitology McGiU University Macdonald College Ste. Anne de Bellevue Quebec, Canada H 9 X 1C0

BRIEFCLINICALOBSERVATIONS 1. Walsh JA: Problems in recognition and diagnosis of amebiasis: estimation of global magnitude of morbidity and mortality. Rev Infect Dis ]986; 8: 228-238. 2. Ravdin JI, Guerrant RL: A review of the parasite cellular mechanisms involved in the pathogenesis of amebiasis. Rev Infect Dis 1982; 4: ]]85-1207. 3. Denis M, Chadee K: Human neutrophils activated by interferon-~ and tumour necrosis factor-a kill Entamoeba histolytica trophozoites in vitro. J Leukocyte Biol (in press). 4. Denis M, Chadee K: Cytokine activation of macrophages for in vitro killing of Entamoeba histolytica trophozoites. Infect Immun 1989; 57:1750-1759. 5. Ruff MR, Gifford GE: Purification and physicochemical characterization of rabbit TNF. J Immunol 1980; 125: ]671-1677. 6. Scuderi P, Sterling KE, Lam KS, et a# Raised serum levels of tumour necrosis factor in parasitic infections. Lancet 1986; I1: 1364-1365. 7. Chadee K, Meerovitch E: The pathogenesis of experimentally-induced amebic liver abscess in the gerbil (Meriones unguiculatus ). Am J Patho11984; 117: 71-82. 8. Denis M, Chadee K: In vitro and in vivo studies of macrophage functions in amebiasis. Infect Immun ]988; 56: 3126-313]. Submitted August 3, 1989, and accepted August 15, 1989


Gastropathy is the leading adverse drug reaction associated with nonsteroidal anti-inflammatory drug (NSAID) use. Prevalence of this complication has ranged in excess of 20% in some studies assessing endoscopic lesions, and more severe complications such as bleeding or perforation have been noted in up to 2% of patients taking these drugs [1-3]. Recently, a prostaglandin E1 analog (misoprostol) has been introduced for treatment of NSAID-induced gastropathy. In s h o r t - t e r m e n d o s c o p i c studies, misoprostol in doses of 200 #g four times a day has been shown to prevent endoscopic lesions in the majority of patients given NSAIDs [4]. A dose of only 400 #g/day has been shown to be nearly as effective as the 800-#g dose and has been associated with fewer side effects [4]. Whether such short-term or even prolonged use of misoprostol is associated with protection from gastric perforation or bleeding induced by NSAIDs has not been established. We report on a young man with Reiter's syndrome who developed NSAID gastropathy that progressed to bleeding despite treatment with misoprostol.

A 20-year-old man presented to the Rheumatology Outpatient Department of the University of Alabama at Birmingham in 1987. He had developed urethritis after a new sexual contact and was treated with minocycline. Soon afterwards he d e v e l o p e d a s y m m e t r i c oligoarthritis and conjunctivitis. He was treated with NSAIDs and then initially with sulfasalazine at a dose of 2,000 mg daily. Because of continued articular symptoms, sulfasalazine was discontinued and he began to receive oral pulse methotrexate in addition to an NSAID for a period of about six months. With improvement of his arthritis, the methotrexate dosage was tapered off and he continued to do well while receiving flurbiprofen at a dose of 100 mg twice a day. Two weeks before hospitalization he complained of epigastric burning and nausea. At that time his hematocrit was 37% and the result of stool examination was negative for occult blood. Treatment with misoprostol at a dose of 100 #g orally four times a day was instituted. Gastrointestinal symptoms comp l e t e l y cleared. H o w e v e r , two weeks after misoprostol treatment was initiated, he passed a melanotic stool and vomited approximately two cups of coffee -ground material. This led to hospitalization. At the time of his admission, his blood pressure was 122/72 mm Hg supine, and 100/65 mm Hg while he was standing. Results of the remainder of physical examination were remarkable for several swollen and t e n d e r i n t e r p h a l a n g e a l joints in the toes and hands. Laboratory data were remarkable for a hematocrit that was initially 34% but decreased to a low of 27%. Metabolic and clotting studies were normal. E n d o s c o p y r e v e a l e d a large area of gastric ulceration. Flurbiprofen was stopped and he was treated with lavage and cimetidine, with control of the bleeding. With the hematocrit stable after four days of observation and no evidence of further bleeding, he was discharged from the hospital. Misoprostol appears to be a very useful drug in prophylactic and symptomatic treatment of NSAIDinduced gastropathy [4]. However, the exact role of this medication in long-term therapy and prevention of perforation and bleeding has not been fully delineated. Our patient

demonstrates that despite symptomatic i m p r o v e m e n t with this medication, progression of gastrop a t h y with bleeding can occur. Whether a higher dose of misoprostol would have prevented the hemorrhagic episode in our patient is speculative at this time. However, it would appear prudent that misoprostol treatment in patients with gastric symptoms presumed due to NSAIDs should be initiated at the higher dose. Similarly, the higher dose of 200 #g four times a day should probably be used as initial treatment in patients with gastric ulceration. As indicated by previous reports and clearly demonstrated by our patient, there certainly can be discordance between symptomatic control and progression of the lesion and hemorrhage in young as well as in elderly patients [5], demonstrating the need for careful follow-up of patients. L o n g - t e r m s t u d i e s are c l e a r l y needed to assess the role of this medication in preventing NSAIDi n d u c e d p e r f o r a t i o n or h e m o r rhage. WARREN D. BLACKBURN, Jr., M.D. GRACIELA S. ALARCON, M.D., M.P.H. University of Alabama at Birmingham Birmingham, Alabama 1. Caruso I, Bianchi P: Gastroscopic evaluation of anti-inflammatory agents. Br Med J ]980; 280: 7578. 2. Bartle W, Gupta A, Lazor J: Nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding: a case-controlled study. Arch Intern Med 1986; 146: 2365-2367. 3. Coles L, Fries J, Kraines R, etak From experiment to experience: side effects of nonsteroidal anti-inflammatory drugs. Am J Med ]983; 74: 820-828. 4. Graham D, Agrawal N, Roth S: Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet i988; I1: 1277-1280. 5. Skander M, Ryan F: Non-steroidal anti-inflammatory drugs and pain-free peptic ulceration in the elderly. Br Med J ]988; 297: 833-834. Submitted July ]8, 1989, and accepted in revised form September 7, 1989

PSEUDOMONAS PUTREFACIENS BACTEREMIA ASSOCIATED WITH SHELLFISH CONTACT P s e u d o m o n a s p u t r e [ a c i e n s is a motile, nonfermentative, oxidasepositive, gram-negative bacillus that is ubiquitous in the environment. It has been isolated from wa-

January1990 The AmericanJournalof Medicine Volume88


cachectin and amebic liver abscess.

BRIEFCLINICALOBSERVATIONS t h a n 50% of the bowel lumen. Pathologic examination demonstrated the adenocarcinomatous nature of the mass. An abdominal...
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