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.

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.

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.

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.

[Familial Mediterranean fever and electroencephalographic changes. A clinical case]. / Febbre familiare mediterranea e alterazioni elettroencefalografiche. Caso clinico.

The Authors describe the case of a non-Hebrew Italian girl suffering from short-lasting fever episodes, associated with abdominal colic, since the age of 3. The occurrence of acute arthrosynovitis during the last episode, at 12 years of age, clinically confirms the diagnosis of familial mediterranean fever, as previously supposed. The increase in urinary coproporphyrins, with normal values of delta-aminolevulinic acid and porphobilinogen poses the problem of the differential diagnosis between hereditary coproporphyria and secondary coproporphinuria. The importance of this case lies in the presence of electroencephalographic alteration since the first years of life, suggesting a temporal epilepsy for which the patient was at length submitted to anti-epileptic treatment. Electroencephalographic alterations, of different type and uneasy interpretation, are described in the literature with a frequency which does not seem accidental. Renal biopsy does not show amyloid, nor the RMN reveals cerebral abnormalities. The anti-epileptic therapy being withdrawn, the patient was treated with daily administrations of colchicine (1 mg/die); 18 months after, she is disease free.

Reversible dilated cardiomyopathy due to growth hormone deficiency.

An unusual case of severe dilated cardiomyopathy is described in a woman with postpartum hypopituitary function, which was characterized by marked decrease of cardiac myofibrils (decreased ratio of myofibrillar volume:cell volume) and somatomedin C deficiency. The patient was treated with a daily intramuscular dose of 4 UI of recombinant human growth hormone for 3 months. Clinical and laboratory assessment and follow-up consisted of noninvasive (echocardiograms, Doppler study, and clinical laboratory tests) and invasive procedures (angiography and endomyocardial biopsy). Morphologic study included optical and electron microscopic examinations and morphometric analysis. The patient exhibited a relevant improvement of cardiac function after recombinant human growth hormone administration. The clinical improvement was confirmed by normalization of electrocardiographic voltages, increased myocardial mass, angiography, and optical and electron microscopic examination, which showed a dramatic recovery of myofibrillar content in myocardiocytes. Furthermore, withdrawal of growth hormone was followed by reduction of electrocardiographic voltages and myocardial mass as well as by impairment of left ventricular function. The authors suggest that there are forms of dilated cardiomyopathy that may benefit dramatically by growth hormone administration. These forms should be identified by growth hormone/somatomedin C axis deficiency and by decrease in myofibrillar content at endomyocardial biopsy.

Catecholamine-induced cardiomyopathy in multiple endocrine neoplasia. A histologic, ultrastructural, and biochemical study.

A catecholamine-induced dilated cardiomyopathy is reported in a patient with multiple endocrine neoplasia, type 3. A histologic and ultrastructural study has been undertaken in cardiac biopsy samples, together with determination of myocardial Ca++ and cellular membrane fatty acids. Contraction band necrosis of cardiocytes with supercontraction of sarcomeres progressing to myofibrolysis and increased levels of myocardial Ca++ have been found as morphologic and biochemical abnormalities, respectively. No lipoperoxidation of cellular membranes or an alpha-adrenergic mediated reduction of coronary supply could be recognized in the study. We indicate a receptor-mediated intracellular Ca++ overload as the main abnormality responsible for myocardial impairment.

Circulating immune complexes detected by a direct nephelometric assay and acute phase proteins in malignant tumors.

Circulating immune complexes (CIC) were previously reported to be higher in extended cancer rather than in localized one, by a few groups of investigators as well as by ourselves. The techniques employed were quite different in each study. We described a "direct" laser nephelometric assay. At the same time we determined the serum levels of 4 acute phase proteins (AFP)--alpha 2 macroglobulin, C reactive protein, haptoglobin, alpha 1 acid glycoprotein--by conventional light scattering method, in order to investigate on other possible "immune-modulating" factors. The possible correlations either with prognosis or clinical stage are looked for; the hypothetical behaviour of CIC as one of the serum "blocking factors" and of acute phase reactant as "immune modulating" proteins are discussed. The data concerning the techniques able to remove CIC from the blood stream of the cancer patients were also showed (plasmapheresis and immunoadsorption).

Episodic angioedema with eosinophilia (Gleich syndrome).

A case of episodic angioedema with hypereosinophilia or otherwise called Gleich's syndrome is reported. The patient was a young woman with a six-year history of recurrent angioedema, itchy urticaria, rapid weight gain and hypereosinophilia. The main clinical, laboratory, and immunological findings included systemic angioedema, urticaria, 12% weight gain and leucocytosis (69.150 WBC/cu mm) with eosinophils of 75.6%. Circulating IgM, IgE, and T-helper lymphocyte were elevated. Skin biopsy showed an important perivascular eosinophil infiltration. The absence of concomitant allergic, malignant and connective disorders, and a dramatic clinical improvement with a fall of the eosinophil count to normal levels following corticosteroid therapy was the basis for our diagnosis.

Measurement of a breast cancer associated antigen detected by monoclonal antibody SP-2 in sera of cancer patients.

An enzyme-linked immuno-absorbent assay has been developed for the detection of a circulating tumor-associated antigen, 90K, recognized by murine monoclonal antibody SP-2 (Iacobelli et al., Cancer Res 46: 3005-3010, 1986). This assay was found to be simple and reproducible. Using this method, 6% of 165 apparently healthy individuals and 15% of 91 patients with benign breast disease showed 90K levels above 1.7 units/ml. Approximately 50% of 129 patients with advanced breast cancer demonstrated serum antigen levels above 1.7 units/ml. All histological types of breast cancer were positive, and no association between the incidence of elevated 90K levels and other prognostic variables could be detected. The titers of 90K were significantly higher in sera from advanced-stage (3 and 4) patients than in those from patients with limited-stage (1 and 2) disease. Elevated 90K levels were also observed in patients with carcinomas of other sites, including gastrointestinal, gynecological, and lung tumors. By means of the immune blotting technique, the antigenic components carrying the determinants in serum and extracts of breast cancer cells have been identified. The levels of 90K did not correlate with those of CA 15-3 or CEA. The measurement of 90K in sera appears to be a useful adjunct to other available assays for the detection and monitoring of breast cancer and other malignant tumors.

Glucocorticoid receptors predict response to combination chemotherapy in patients with acute lymphoblastic leukemia.

Glucocorticoid receptor levels were quantified in leukemic blasts from peripheral blood of 86 patients with acute lymphoblastic leukemia. Subsequent achievement of complete remission correlated with high receptor levels. Forty-seven of 50 patients with leukemic cells containing more than 6,000 receptor sites and 22 of 36 patients with cells containing less than 6,000 receptor sites achieved remission. The study of glucocorticoid receptors in leukemic cells may predict response to combination chemotherapy in acute lymphoblastic leukemia patients.

Sex steroid receptors in normal and malignant human vulvar tissue.

Receptors for estrogens, progesterone and androgens were assayed in 6 specimens of normal vulvar tissue and in 9 specimens of carcinomatous vulvar tissue. These receptors were not always present in all specimens examined. In both normal and carcinomatous tissues receptor concentration was highly variable. Malignant tissues did not show significant changes in values compared to normal tissue.

Primary aldosteronism: complete remission after adrenal venography.

A remission of adrenal adenoma producing aldosterone is described as a consequence of adrenal venous catheterization. The patient did not undergo surgery but she was kept on frequent clinical controls. The complete remission of the syndrome is still persisting three years after the incident. Since adrenal insufficiency is described after adrenal venous catheterization, the authors suggest that this procedure is to be restricted to well selected patients. When this incident occurs in pathological glands, a remission of endocrine syndrome may be expected.