G. Gambassi

Impairment of lymphocyte activities in depressed aged subjects

Lymphocyte activities were determined in a population of 26 institutionalized aged subjects, selected as healthy according to the SENIEUR protocol and previously reported to display immunological and endocrinological abnormalities correlated with depressive disorders. The lymphocyte mitotic response to PHA, which was reduced in aged as compared to adult subjects, was found to be significantly lower and negatively correlated with the depression score in the elderly subjects. In supernatants of PHA-stimulated lymphocyte culture from aged subjects, IL-2, IL-4 and gamma-IFN levels were very low and more severely affected in the depressed aged group. Each cytokine production was negatively correlated with age and depression score. NK activity was lower in the aged and it could be augmented by the addition of IL-2 or alpha-IFN, even though to a lesser extent than in the adult subjects. The nondepressed aged displayed higher levels of IL-2 inducible NK activity than the depressed aged subjects. IL-2 and alpha-IFN stimulated NK activities were negatively correlated with depression score. The present work indicates that the psychological status could affect lymphocyte reactivity in the aged. Given the relatively high frequency of affective disorders in these subjects, the psychological status should be considered in studies of immune senescence.

Focal ultrasound lesions in liver cirrhosis diagnosed as regenerating nodules by fine-needle biopsy

In the period 1985–1988, 62 focal liver lesions in 58 cirrhotic patients were studied by ultrasonography; 12 of these focal lesions were documented to be regenerating lesions by echo-guided fine-needle biopsy. During an average follow-up period of 10.2 months (range 3–22 months), hepatocellular carcinoma was subsequently found in 10 of the cases of regenerating nodules, whereas the initial diagnosis of regenerating nodule was confirmed in the remaining two cases. Based upon this finding, it is suggested that every focal mass visualized by ultrasonography in a cirrhotic liver should either be considered to be a neoplastic lesion or at least a preneoplastic lesion if the possibility of either a metastatic or benign lesion (eg, hemangiomas, focal fatty liver change areas) can be excluded. Therefore either fine-needle aspiration or biopsy of all ultrasonographically revealed mass lesions within a cirrhotic liver is advised, such that early appropriate treatment for hepatocellular carcinoma can be instituted.

The efficacy of chemotherapy with mebendazole in human cystic echinococcosis: long-term follow-up of 52 patients.

Sixty patients with Echinococcus granulosus infection of the liver, lungs, bone and/or soft tissues were treated for several months with oral mebendazole (50-60 mg kg-1 day-1), in divided doses after fat-rich meals, either without surgery (WS), post-surgery (PS) or pre- and post-surgery (PPS). Long-term follow-up, possible for 52 of the patients, showed that WS, PS and PPS patients have so far remained disease-free following treatment for (means +/- standard deviations) 65.5 +/- 37.7, 82.5 +/- 37.0 and 84.1 +/- 28.3 months, respectively. Ultrasound and computed tomography scans were similar in WS and PPS patients post-treatment. Blood eosinophil levels, which were sometimes elevated initially, returned to normal in all patients and this decrease indicated cyst degeneration before this was evident on the scans. Treatment of patients with cystic echinococcosis may no longer require surgery.

High-dose folinic acid (HDFA) combined with 5-fluorouracil (5-FU) in first line chemotherapy of advanced large bowel cancer.

The therapeutic activity of 5-FU in large bowel cancer is enhanced by increasing the intracellular pool of reduced folates. We treated 45 patients with advanced colon cancer with HDFA and 5-FU for 5 consecutive days. None had been given previous radio- or chemotherapy. All had measurable disease. Not one complete response was observed. Thirteen of the 39 evaluable patients showed partial response. Median duration of response was 9+ months. The probability of 50% survival was 15 months for all evaluable patients. There was no case of severe toxicity and the principal toxic effects were oral mucositis and diarrhea. To date, HDFA + 5-FU is one of the most effective treatments for large bowel cancer.

Immune parameters in a populatio of institutionalized elderly subjects: influence of depressive disorders and endocrinological correlations

Twenty-six institutionalized elderly subjects, selected as healthy according to the SENIEUR protocol, were compared to adult controls to establish correlations between affective disorders and immune abnormalities and to investigate underlying neuroendocrine mechanisms. After an extensive psychodiagnostic examination, 35% of the aged subjects were classified as depressed. Cutaneous delayed hypersensitivity tests showed reduced responses in the aged, but no correlation was found with the psychological status. Examination of the peripheral blood lymphocyte subsets revealed no imbalance in the percentages of CD3+, CD4+, CD8+ cells in the aged. A slight reduction in the CD4+/CD8+ cell ratio could however be detected in the non-depressed aged, as compared to adult controls. The CD4+/CD45R+ cell subset was reduced in non-depressed aged. The percentage of B lymphocytes was reduced in the aged, mostly in the non-depressed subjects. No changes were detected in the percent of OKDR+ cells. The percentage of CD16+ cells was found unchanged, while that of Leu7+ cells was significantly higher in the aged than in the adults and in the non-depressed than in the depressed aged. Leu7+ cell levels were negatively correlated with the depression score. On double labelling, the percent of CD16+/Leu7+ cells appears increased in the subgroup of depressed aged and positively correlated with age. Plasmatic and urinary cortisol levels were both positively correlated with depression score. Urinary cortisol level was higher in the depressed aged. These parameters, as well as plasmatic ACTH, beta-endorphin and urinary catecholamines, were not correlated with immune responses. Based on these findings, we recommend that the neuroendocrinological conditions should be taken into account when healthy subjects are examined in studies of immune senescence.

Latent Coagulation Disorders Evaluated by the Assay of Plasma Thrombin-Antithrombin III Complexes in a Large Series of ‘Solid Tumours’

Coagulation disorders are frequently detected in patients affected by different tumours even though clinical symptoms occur in a very small percentage of such subjects. Coagulation processes are probably involved in the mechanism of metastatic spread. We assayed the plasma levels of thrombin-antithrombin III (TAT) complexes in a group of 276 patients with several tumours in different stages in order to achieve a better understanding of the complex interactions between coagulation disorders and either tumour growth or metastatic spread. High levels of TAT complexes were found in 51% of localized, 66.3% of metastatic and 58.3% of patients with no evidence of disease; a statistically significant difference was observed comparing metastatic cancer either with localized (p < 0.00015) or with free-of-disease (p < 0.004) groups. Gastrointestinal tract neoplasms showed higher levels of TAT complexes in the metastatic than in the localized group. No difference was seen between small-cell and non-small-cell lung-localized cancer. Our results confirm the frequent coexistence of cancer and subclinical blood coagulation disorders. The evidence of higher levels of TAT complexes in metastatic cancer than in the other groups could be related to the mechanisms involved in tumour spread.

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.

Clinical suspicion of pancreatic neoplasm: does echo-guided fine-needle biopsy modify patient management?

SummaryThe following parameters were retrospectively evaluated in 64 patients with suspected pancreatic neoplasm: (1) time required to obtain cytohistologic diagnosis, (2) days in hospital, (3) number and type of surgical operations, and (4) total hospital costs. Echo-guided fine needle biopsy (FNB) was performed on 34 patients (FNB group) and in a further 30 patients diagnostic workup did not include percutaneous biopsy (laparotomy group). Both diagnostic and hospital stay were shorter (8 and 7 days, respectively) in the FNB group than in the laparotomy group. In the FNB group, surgery was avoided in 18 patients, while in the laparotomy group 18 explorations proved diagnostic alone. Finally, FNB was shown to reduce hospital costs by 23%.

Ultrasound-Doppler diagnosis of Budd-Chiari syndrome

We report a case of apparently idiopathic Budd-Chiari syndrome, diagnosed by ultrasound and Doppler sonography, in a patient with latent myeloproliferative disease. This case proves that Doppler sonography shows in the hepatic veins a flow pattern suggestive of partial thrombotic obstruction. Moreover, we suggest that the search for a latent myeloproliferative disorder, by means of the spontaneous erythroid colonies formation in culture of bone marrow or blood mononuclear cells, should be routinely included in the diagnostic evaluation of each case of hepatic vein thrombosis without other recognizable causes.

Non-Hodgkin Lymphoma Associated with Double Monoclonal Immunoglobulin

We describe an unusual case displaying the features of double monoclonal gammapathy (IgM-kappa plus IgG-lambda) associated with non-Hodgkin lymphoma (NHL). In the last years monoclonal gammapathies have been sometimes found to be associated with NHLs; it is a very peculiar occurrence the association between a different class double monoclonal gammapathy and NHL, as the case reported in this paper.