Giant cell myocarditis responding to immunosuppressive therapy.

An unusual case of giant cell myocarditis presenting with cardiogenic shock that dramatically responded to conventional dose of steroids and azathioprine is reported. Cardiac recovery was rapid, complete (left ventricular ejection fraction rose to 55% from 10%), and was accompanied by the disappearance of the inflammatory infiltrates including giant cells in the control endomyocardial biopsy. Maintenance of the recovery at 16 months of follow-up on a low dose of azathioprine suggests that giant cell myocarditis might be a heterogeneous disease having either a negative untreatable trend necessitating cardiac transplantation, or a curable substrate responding to immunosuppressive drugs.

Five-day regimens containing ranitidine bismuth citrate plus high-dose clarithromycin and either amoxycillin or tinidazole for Helicobacter pylori infection.

BACKGROUND: Ranitidine bismuth citrate (RBC)-based triple therapies for a period of 7 days have proved to be an effective treatment for Helicobacter pylori. AIM: To investigate the eradication efficacy, safety profile and patient compliance of two RBC-based triple therapies given for 5 days. METHODS: Eighty H. pylori-positive patients with dyspeptic symptoms, referred to us for gastroscopy, were consecutively enrolled in this prospective, randomized, open-label study. These patients were randomly assigned to receive a 5-day course of RBC 400 mg b.d. plus clarithromycin 500 mg b.d. and either tinidazole 500 mg b.d. (RBCCT group) or amoxycillin 1 g b.d. (RBCCA group). The H. pylori status was assessed by means of histology and rapid urease test at entry, and by 13C-urea breath test 8 weeks after the completion of treatment. RESULTS: All enrolled patients completed the study. Thirty-seven of 40 patients treated with RBCCT (both PP and ITT analysis: 93%; 95% CI: 80-98%) and 35 of 40 in the RBCCA group (both PP and ITT analysis: 88%; 95% CI: 73-96%) returned H. pylori-negative. Slight or mild side-effects occurred in 4/40 patients (10%) in the RBCCT group and in 5/40 (12%) in the RBCCA group. CONCLUSIONS: This is the first study demonstrating the efficacy of RBC-based triple therapies given for only 5 days. RBC regimens containing high-dose clarithromycin and either amoxycillin or tinidazole prove to be well tolerated, safe and preserve good eradication rates even when administered for a shorter than conventional duration.

Resolution of syndrome X after eradication of virulent CagA-positive Helicobacter pylori.

A 42-year-old man with chest pain was found to have ST depression in leads V1 through V4. The coronary arteries appeared normal on angiography. Positive results of ventricular pacing and acetylcholine test led to a diagnosis of syndrome X. Other studies revealed gastritis due to CagA-positive Helicobacter pylori. Classic therapy for angina did not resolve chest pain, but eradication of H. pylori led to disappearance of symptoms and negative test results.

No evidence of Helicobacter pylori sequences in pancreatic juices of patients affected by chronic pancreatitis.

BACKGROUND: The course of chronic pancreatitis is often unpredictable and many factors are likely to be involved in the progression of the disease. In physiological condition, pancreatic juice exerts significant antibacterial activity, which is impaired in patients with chronic pancreatitis. AIM: Hypothesizing that Helicobacter pylori could, in these conditions, lead to an ascending infection, we aimed to assess the presence of H. pylori sequences in pancreatic juices of patients with chronic pancreatitis. METHODS: 40 patients (mean age 52+/-3 yr) with alcoholic chronic pancreatitis and H. pylori infection were examined. Pancreatic juices were collected during endoscopic retrograde cholangiopancreatography. Using polymerase chain reaction (PCR) with two primers homologous to a portion of urease-C gene, H. pylori DNA was detected. Gastric biopsies, microscopically positive to H. pylori were used as positive controls. RESULTS: All gastric biopsies produced H. pylori-specific DNA products. Conversely, no H. pylori urease-C gene sequences have been detected in any of the pancreatic juices. CONCLUSION: Our data suggest that the impaired antibacterial activity of pancreatic juices in patients affected by chronic pancreatitis does not have a permissive role for a superimposing H. pylori infection in the pancreas. The possibility that Helicobacter species other than pylori may be involved in a superimposing infection requires further investigation.

Necrotizing myocardial vasculitis in Churg-Strauss syndrome: clinicohistologic evaluation of steroids and immunosuppressive therapy.

Treatment of cardiac dysfunction associated with Churg-Strauss syndrome (CSS) is empiric since the histologic findings provided by endomyocardial biopsy are rare and often nondiagnostic. Myocardial necrotizing vasculitis presenting as restrictive cardiomyopathy has not been reported before. A case of CSS, presenting with fever and progressive heart failure due to pericarditis, eosinophilic endomyocarditis, and myocardial necrotizing vasculitis, is reported. Cardiac involvement assessed by noninvasive (cardiac two-dimensional echocardiogram and nuclear magnetic resonance [NMR] imaging) and invasive (cardiac catheterization, angiography, and biopsy) studies showed a moderate degree of pericardial effusion and left ventricular (LV) dysfunction (ejection fraction 0.40), severe diastolic dysfunction (increased right and LV filling pressure with a dip and plateau pattern) and a severe reduction of cardiac index (1.6 L/min/m2). Histologic characteristics showed marked eosinophilic infiltration of the endocardium and myocardium with myocitolysis and fibrinoid necrosis of arterioles, venules, and capillaries. Combination therapy of steroids and cyclophosphamide resulted in both a clinical (regression of pericardial effusion, normalization of systolic and diastolic dysfunction, and increase of cardiac index to 2.8 L/min/m2) and histologic (sequential endomyocardial biopsies at 1, 3, and 6 months of follow-up) resolution of cardiac involvement. No recurrences were registered at 12-month follow-up with the patient receiving a maintenance drug regimen.

Acute liver injury related to the use of niperotidine.

BACKGROUND/AIMS: H2-receptor antagonists are widely used for the therapy of peptic disease, since they ensure a protracted and intense inhibition of gastric acidity. Niperotidine (piperonyl-ranitidine) is a new H2 blocking agent recently proposed for clinical use. METHODS: Twenty-five cases of acute hepatitis associated with the use of niperotidine were reported in Italy between March and August 1995. Intercurrent viral infections, recent drug and alcohol consumption and blood transfusions were excluded as causes. RESULTS: All patients showed an increase in the parameters of liver cell injury and the clinical symptoms of acute hepatitis. After withdrawal of the drug, all patients showed a good outcome, except one who developed a fulminant hepatitis and died from digestive tract bleeding. CONCLUSIONS: The absence of other causes of acute liver injury suggests that the observed liver injury may be a niperotidine-adverse reaction. Moreover, the lack of a relationship between the dose of the drug and the degree of liver damage, the variable latent period and the rarity and unpredictability of the injury are suggestive of an idiosyncratic reaction.

Influence of alcohol on gastrointestinal motility: lactulose breath hydrogen testing in orocecal transit time in chronic alcoholics, social drinkers and teetotaler subjects.

BACKGROUND/AIMS: The gastrointestinal tract is directly affected by the ingestion of alcohol. While the effect of acute ingestion of alcohol on the motility of the small intestine is well known, the influence of chronic intake of moderate amounts of alcohol and chronic alcoholism on gastrointestinal motility remains poorly understood. The aim of this study was to examine the orocecal transit (OCt) times in patients with chronic alcoholism and in "social drinkers" and compare them with a group of healthy teetotaler subjects, to assess the effects of chronic aleohol consumption on gastrointestinal transit through the application of a non-invasive technique: the hydrogen breath test. METHODOLOGY: Thirty-one alcoholics were enrolled in the study. The control groups consisted of 31 healthy social drinkers and 24 healthy teetotaler subjects. OCt time was assessed using the hydrogen breath test after the administration of 10 g of lactulose. RESULTS: The OCt time in patients with alcoholism was significantly delayed as compared with the social drinkers (p < 0.001) and healthy teetotaler subjects (p < 0.001); the OCt time in social drinkers was significantly longer than in healthy teetotaler subjects (p < 0.05). In the alcoholic group, there was no significant correlation between the OCt time and daily alcohol intake or years of alcohol addiction. CONCLUSION: Our results show a significant prolongation of the OCt time, both in patients with alcoholism and in social drinkers, as compared to teetotaler subjects. Our findings of an increased OCt time related to the consumption of alcohol could support the hypothesis of the toxic effect of ethanol on smooth muscle contractile proteins of the small intestine and on vagal function.

Peritoneal mesothelioma in recurrent familial peritonitis.

A 39-year-old man had a 2-year history of fatigue, weight loss, drug-resistant ascites, and decreased intestinal motility. During adolescence he began to suffer frequent episodes of acute benign peritonitis that spontaneously subsided at age 35. The fact that his younger brother was taking colchicine for the same symptoms led us to diagnose familial Mediterranean fever (FMF). The medical workup revealed uniform thickening of the intestinal wall with no signs of amyloidosis. Exploratory laparotomy revealed diffuse peritoneal mesothelioma that proved to be unresponsive to chemotherapy. There was no history of asbestos exposure. It is probable that the chronic peritoneal inflammation was responsible for the development of this tumor, although in almost all cases of FMF this phenomenon causes only limited peritoneal fibrosis or, less commonly, encapsulating peritonitis. A computerized search of the literature indicates that this is the second report of peritoneal mesothelioma associated with FMF.

[The modes of transmission of Helicobacter pylori infection]. / Modalità di trasmissione dell'infezione da Helicobacter pylori.

Helicobacter pylori plays an essential role in the development of several both acid-related and neoplastic gastroduodenal pathologies. There are still uncertainties about the transmission routes and the sources of H. pylori infection. Man is the only well established "reservoir" of H. pylori, while the role of other mammalians (cat, pig, primates), as sources of infection, is still controversy. Literature data suggest four different modalities of transmission of the infection: faeco-oral, oro-oral, gastro-oral, gastro-gastric. By faeco-oral route, the bacterium, excreted with faeces, might colonize water sources, becoming so available to be transmitted to man and other mammalians. By oro-oral route, H. pylori, which colonizes dental plaque and saliva, may be transmitted by saliva to other individuals. The gastro-oral route is the typical modality of transmission in the childhood, when H. pylori uses the mucous achlorhydric vomitus of the children to infect a new host. Finally, by gastro-gastric route the bacterium might be transmitted by endoscopic procedures. In conclusion, we believe the different modalities of transmission may be contemporaneously involved, since none per se is able to explain the widespread occurrence of H. pylori infection.

Paradoxical inhibition of cardiac lipid peroxidation in cancer patients treated with doxorubicin. Pharmacologic and molecular reappraisal of anthracycline cardiotoxicity.

Anticancer therapy with doxorubicin (DOX) and other quinone anthracyclines is limited by severe cardiotoxicity, reportedly because semiquinone metabolites delocalize Fe(II) from ferritin and generate hydrogen peroxide, thereby promoting hydroxyl radical formation and lipid peroxidation. Cardioprotective interventions with antioxidants or chelators have nevertheless produced conflicting results. To investigate the role and mechanism(s) of cardiac lipid peroxidation in a clinical setting, we measured lipid conjugated dienes (CD) and hydroperoxides in blood plasma samples from the coronary sinus and femoral artery of nine cancer patients undergoing intravenous treatments with DOX. Before treatment, CD were unexpectedly higher in coronary sinus than in femoral artery (342 +/- 131 vs 112 +/- 44 nmol/ml, mean +/- SD; P < 0.01), showing that cardiac tissues were spontaneously involved in lipid peroxidation. This was not observed in ten patients undergoing cardiac catheterization for the diagnosis of arrhythmias or valvular dysfunctions, indicating that myocardial lipid peroxidation was specifically increased by the presence of cancer. The infusion of a standard dose of 60 mg DOX/m(2) rapidly ( approximately 5 min) abolished the difference in CD levels between coronary sinus and femoral artery (134 +/- 95 vs 112 +/- 37 nmol/ml); moreover, dose fractionation studies showed that cardiac release of CD and hydroperoxides decreased by approximately 80% in response to the infusion of as little as 13 mg DOX/m(2). Thus, DOX appeared to inhibit cardiac lipid peroxidation in a rather potent manner. Corollary in vitro experiments were performed using myocardial biopsies from patients undergoing aortocoronary bypass grafting. These experiments suggested that the spontaneous exacerbation of lipid peroxidation probably involved preexisting Fe(II) complexes, which could not be sequestered adequately by cardiac isoferritins and became redox inactive when hydrogen peroxide was included to simulate DOX metabolism and hydroxyl radical formation. Collectively, these in vitro and in vivo studies provide novel evidence for a possible inhibition of cardiac lipid peroxidation in DOX-treated patients. Other processes might therefore contribute to the cardiotoxicity of DOX.

Chronic pancreatitis prevalence in liver cirrhosis. Morphological and functional study.

Ductal pancreatic changes and functional exocrine assessment have been studied, in a group of 60 cirrhotic patients. In these patients the aetiology of cirrhosis was alcoholism in 35, hepatitis B virus-hepatitis C virus infection in 19, primary biliary cirrhosis in 2 and not determinable in 4. Eighteen patients (30%) showed an endoscopic retrograde pancreatography picture consistent with chronic pancreatitis (14 mild, 2 moderate and 2 severe). Mild pancreatographic changes were present in 7 alcoholic (20%) and in 7 non-alcoholic cirrhosis patients (28%). Moderate and severe abnormalities were present only in alcoholic cirrhosis (4 patients, 11.4%). No correlation was found between presence or pancreatopathy degree and Child-Pugh score or cirrhosis duration. Functional exocrine tests were abnormal only in severe endoscopic retrograde pancreatography picture. Mild type ductal lesions can mimic either age-dependent changes or chronic pancreatitis. The absence of impaired functional tests makes it impossible to discriminate between these two possibilities. These findings emphasize that in our cirrhotic group the prevalence of chronic pancreatitis (with a moderate or severe endoscopic retrograde pancreatography picture) is low (6.6%) and alcoholism is always present. Possibly, cirrhosis with secretion of high-volume low protein concentration juice confers a protective effect on the pancreas.

Acute myocarditis and left ventricular aneurysm as presentations of systemic lupus erythematosus.

A case of systemic lupus erythematosus (SLE) associated with fever, heart failure, and left ventricular (LV) aneurysm is reported. A diagnosis of SLE was suspected owing to the presence of active lymphocytic myocarditis and fibrinous endocarditis at LV endomyocardial biopsy and was confirmed by identification of 4 of the 11 criteria proposed by the American Rheumatism Association for the definition of SLE. A 2-month period of steroid therapy was followed by a remarkable recovery of LV function and progression of endomyocarditis to a healed phase at control LV biopsy. The LV aneurysm disappeared, likely because thrombosis occurred as a result of the hypercoagulable state accompanying the presence of anticardiolipin antibodies. This is the first reported case of LV aneurysm induced by SLE and is a rare clinicohistologic documentation of the effectiveness of steroid treatment on lupus endomyocarditis.

Pancreatic juice 90K and serum CA 19-9 combined determination can discriminate between pancreatic cancer and chronic pancreatitis.

OBJECTIVES: Differential diagnosis of pancreatic cancer versus chronic pancreatitis may be difficult. The aim of this study is to determine whether a group of tumor-associated antigens could differentiate between the two pathologies. METHODS: CA 19-9, TAG-72, CAR-3, and a newly discovered antigen termed "90K" were determined in the serum and in the pancreatic juice of 19 patients with pancreatic cancer, 20 patients with chronic pancreatitis, and seven controls with lithiasis of extrapancreatic bile ducts. RESULTS: The serum antigen levels of all three markers except 90K were significantly higher in pancreatic cancer than in chronic pancreatitis. High correlations were found between serum CA 19-9 and both TAG-72 and CAR-3. 90K did not correlate with other markers. In pancreatic juice, only 90K values were significantly higher in chronic pancreatitis than in pancreatic cancer, and only 90K and CA 19-9 were significantly correlated. At the stepwise discriminant analysis, serum CA 19-9 and pancreatic juice 90K had independent diagnostic roles. Used in combination, they correctly identified 84.2% of pancreatic cancer and 90% of chronic pancreatitis. CONCLUSIONS: These data suggest that pancreatic juice 90K and serum CA 19-9 can discriminate between chronic pancreatitis and pancreatic cancer. The data further support the complementary use of tumor-associated antigens along with other diagnostic tools.

Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas.

BACKGROUND/AIMS: Fish oil supplementation can reduce cytokinetic anomalies in the flat rectal mucosa of patients with sporadic colorectal adenoma. This study attempted to identify an optimum dose for fish oil supplementation and evaluate the persistence of its effects during long-term administration. METHODS: In a double-blind study, 60 patients with sporadic adenomas received 2.5, 5.1, or 7.7 g of fish oil per day or placebo for 30 days. [3H]thymidine autoradiographic labeling indices were calculated in flat rectal mucosal biopsy specimens collected before and after supplementation. In a subsequent study, 15 patients with polyps received 2.5 g of fish oil per day. Proliferative parameters, mucosal fatty acids, and mucosal and plasma alpha-tocopherol levels were evaluated before, during, and after 6 months of supplementation. RESULTS: Mean proliferative indices and mucosal arachidonic acid levels decreased significantly (and to similar degrees) in all treated groups, whereas mucosal eicosapentaenoic and docosahexaenoic acid levels increased. Significantly reduced proliferation was observed only in patients with abnormal baseline patterns. These effects persisted during long-term, low-dose treatment. A transient reduction in mucosal (but not plasma) alpha-tocopherol levels was observed after 1 month of treatment. Side effects were insignificant. CONCLUSIONS: Low-dose fish oil supplementation has short-term and long-term normalizing effects on the abnormal rectal proliferation patterns associated with increased colon cancer risk.

Assay, isolation and characterization of circulating immune complexes from serum of gastrointestinal cancer, stage III and IV melanoma and chronic inflammatory bowel disease patients.

Circulating immune complexes (CIC) have been detected in several autoimmune diseases, and studies have also suggested that CIC provide a useful tool as tumor markers. In order to identify differences or similarities in antigenic composition, CIC from 23 patients with gastrointestinal (GI) tumors, from 20 patients with stage III and IV melanoma and from 6 patients with inflammatory bowel disease (IBD) were studied. Serum from all GI, melanoma and IBD patients showed higher levels of CIC than controls. SDS/PAGE electrophoresis under reducing conditions revealed some differences between cancer and IBD patients as far as the CIC protein composition was concerned. In melanoma patients, two fast-migrating bands, in the regions of 71-74 and 30-49 kD, were found, consistent with previously isolated and characterized antigens described in the literature.

Acute myopathy associated with chronic licorice ingestion: reversible loss of myoadenylate deaminase activity.

A patient with acute rhabdomyolysis and absence of myoadenylate deaminase (MADA) associated with chronic licorice intoxication is presented. Clinical and laboratory examination of the patient and morphologic study over skeletal muscle were performed. The major effect of licorice intoxication is hypokalemia, which may explain most of the observed clinical symptoms and morphological changes. The absence of MADA may be a consequence of the direct toxic effect of licorice glycosides. To our knowledge, this is the first report in which a lack of MADA and chronic licorice intoxication has been shown to be associated with clinical, histochemical, biochemical, and morphological changes, which were completely reversed with potassium supplementation and licorice withdrawal.