Biomedical subjects
Publications and source records attributed to C Pizzi.
Donor organ procurement is a world-wide problem. In Italy it is particularly so and the reasons for this are investigated. An overall increase in the number of donors has been noted in 1994 and the first 8 months of 1995, and ways of continuing this encouraging trend should be pursued by improvements in education, legislation, and hospital organization.
We prospectively evaluated the frequency of lymphadenopathy in the right upper abdominal quadrant as detected by sonography in 650 consecutive unselected patients, after excluding patients with a known lymphoma or abdominal carcinoma and patients with acquired immunodeficiency disease. Evidence of enlarged lymph nodes (few in number, with an elongated shape and isoechoic to the liver, 8 to 22 mm in size), found primarily in the gastrohepatic ligament and porta hepatis, was seen on sonographic scans in 106 patients (16.3%). Associated conditions in 69 of 106 patients (65%) were hepatobiliary or pancreatic diseases and, less frequently, other benign entities (12 patients; 11.3%); in 25 cases (23.5%) no significant abdominal or systemic disease was present. Comparison with CT or surgical findings, or both, was available in 36 cases. We conclude that lymphadenopathy in the right upper abdominal quadrant may be found in relation to different non-neoplastic conditions as well as in the absence of any significant intra-abdominal disease. The frequency of this finding on sonographic scans must be recognized to prevent misdiagnosis of lymphoma or metastatic disease as well as to avoid overstaging of local (hepatobiliary, pancreatic, gastric) neoplasms.
Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) have frequent extraintestinal (hepatobiliary, cutaneous, ocular, articular, urinary) complications. On the contrary, no data are available about possible thyroid involvement. We studied thyroid morphology and function in 39 patients affected with active IBD (13 UC; 26 CD) before (all) and 45 and 90 days after onset of therapy (21/39), and in 55 normal control subjects. Every time, the following exams were performed: thyroid US (parenchymal assessment, thyroid volume calculation), hormone and immunologic assays (T3, T4, FT3, FT4, TSH; antithyroglobulin and antithyroid microsomal/peroxidase antibodies). A statistically significant increase in thyroid volume was found in IBD (mean: 22.1 ml) compared to control subjects (mean: 15.6 ml), more frequently in CD (18/26 patients; 69.2%) than in UC (2/13 patients; 15.4%). Parenchymal structure was inhomogeneous in the two groups of patients (88.4% CD; 15.4% UC) more frequently than in control subjects (12.7%). Hormone assays demonstrated increased FT4 values in UC (9/13 patients; 69.2%) and decreased T4 values in CD (14/26 patients; 53.8%). IBD patients increased frequency of antithyroglobulin and antithyroid microsomal/peroxidase antibodies. Such abnormalities subsided only partially after therapy. Our data suggest that in IBD there is a frequent thyroid involvement with morphological, hormone, and immunologic abnormalities.
Genomic instability plays a key role in hereditary nonpolyposis colorectal cancer and in a significant sub-set of non-hereditary colorectal tumors. Recent evidence suggests that microsatellite instability also occurs in various sub-sets of common, non-hereditary forms of extra-colorectal carcinoma. To investigate the role of microsatellite instability in breast cancer, and to correlate this type of alteration with clinico-pathological characteristics, including tumor proliferative activity, we analyzed the status of 8 different microsatellite loci in 28 cases of primary mammary carcinoma. For this purpose, microsatellite banding patterns were compared in paired breast-cancer/peripheral-blood DNA samples. Microsatellite instability was observed in 6/28 (21%) of the cases. Four of the 6 tumors had low proliferative activity, one had high proliferative activity, and in one case proliferative activity values were not available. All chromosomal loci investigated demonstrated microsatellite instability in one or more representative tumors of the series. Shifts in length larger than 2 bp were the most frequent change. Microsatellite instability significantly correlated with the lobular histotype, and with lymph-node involvement. A trend was also observed associating microsatellite instability and large tumor size.
Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells.
Cell kinetics is a predictive parameter of breast-cancer aggressiveness, and mutations occurring in mammary tumorigenesis may favor uncontrolled cell proliferation. In this study, cell kinetics, clinico-pathological characteristics and genetic alterations at the int-2, bcl-1, c-myc, c-erbB-2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at more than one locus was also studied. Tumor-proliferative activity was evaluated by determination of the thymidine labeling index (TLI). Amplification (AMP) of int-2 was observed in 11.2%, of bcl-1 in 9.4%, of c-myc in 5.7% and of c-erbB-2 in 8.6% of the carcinomas. Loss of heterozygosity (LOH) at the DF3 locus was detected in 13.9% of the tumors. Genetic alterations demonstrated a significant association with patient's age and high TLI values. AMP and LOH+AMP did not appear to be statistically related to histotype, histological grade, tumor size or lymph-node status. Alone, allele loss at the DF-3 locus was not significantly associated with any of the clinico-pathological characteristics studied. Alterations at more than one locus, including int-2/bcl-1, int-2/c-myc, int-2/bcl-1/c-erbB-2, and c-myc/DF3, were detected in 11.1% of the tumors. Multiple mutations were found only in less differentiated tumors, which included the 2 cases from the youngest patients of the series.
A single fetal ultrasonogram was obtained between the 20th and 40th weeks of gestation in 327 pregnancies. Fetal body weight was calculated with standard methods and fetuses were classified as appropriate for gestational age (303 fetuses), large for gestational age (four fetuses), or small for gestational age (20 fetuses). Fetal liver weight was estimated on the basis of longitudinal, anteroposterior, and cephalocaudal liver dimensions multiplied by a constant (k) of 0.42 determined experimentally in a previous study of adult livers. Estimated liver weights in appropriate for gestational age fetuses were not statistically different from published standards based on autopsy findings (P < 0.005). Similar findings were obtained in two other normal pregnancies examined serially until delivery. Estimation of fetal liver weight appears to be an accurate and reproducible method and may enhance sonographic assessment of fetal growth abnormalities and conditions with fetal liver involvement.
The most relevant changes which have taken place in the NITp in the nineties include the introduction of HLA-DRB1 matching, the extension of both recipient and donor selection criteria, and an increase in donor procurement and consequently, in transplantation activity. Some of the changes in policy resulted from extensive analysis of our previous experience. For the future years, the NITp has set the following priorities: Consolidate the increase of donor procurement activity registered in the past 15 months by educational campaigns for health workers and the public, and organizational measures aimed at strengthening ICUs, nominating transplant coordinators and introducing a system of reimbursement for organs procured. Improve the quality of results in terms of patient rehabilitation and cost-benefit through: continued evaluation of protocols for patient admission on the waiting lists and careful selection of donors; and prospective use of genomic HLA Class II matching and also consider genomic typing for HLA Class I which is almost a reality. Establish a single pool of patients on the waiting list evaluated according to common protocols with the possibility of performing the transplant in each of the authorized centers in turn, respecting the best HLA match and the local use of organs. Finally, standards for donor treatment, organ procurement, histocompatibility testing and transplantation must be established. For this purpose, accreditation programs which have begun to be applied in Europe seem to be the adequate tool.
We analysed the immunohistochemical expression pattern of the distinct carbohydrate epitopes of the TAG-72 molecule, defined by the monoclonal antibodies (MAbs) B72.3, CC-49 and CC-83, in 92 breast carcinomas of different histological type, and in other histological components identified in the mammary tissue samples studied. The results were correlated with the clinico-pathological characteristics of the tumours, and with their proliferative activity, assessed by thymidine labelling index (TLI). Expression of the TAG-72 epitopes was detected in all the tumour histotypes analysed, but patterns of immunoreactivity tended to vary in relation to type and level of differentiation. The comparative analysis of the reactivities of the three anti-TAG-72 MAbs revealed differences in their ability to recognise neoplastic lesions. MAb CC-49 reacted with the highest percentage of tumours (82%), and also tended to yield the highest percentages of immunoreactive cancer cells, while B72.3 and CC-83 reacted with lower percentages of tumours (respectively, 55 and 51%), and identified lower percentages of immunoreactive cells. High levels of expression of the three TAG-72 epitopes were detected in areas of in situ ductal carcinoma. Comparatively lower levels of immunohistochemical positivity were found in atypical epithelial hyperplasia, normal mammary epithelium and epithelium with cystic disease. TAG-72 epitope expression was correlated with prognostic parameters. The synchronous expression of the three epitopes significantly correlated with large tumour size (> 2 cm), and with high histological grade. No correlations could be demonstrated between TAG-72 phenotypes and nuclear grade, lymph node status and proliferative activity (high versus low).
Three patients fulfilling criteria for Sudeck's atrophy (reflex sympathetic dystrophy syndrome--RSDS) are described and etiological, pathogenetic and clinical features of the disease are reviewed. RSDS is associated with a wide variety of precipitating factors, each of whom, often in concomitance with metabolic diseases and psychiatric disturbances, may cause the same clinical syndrome, which continues in a "vicious circle" of feed-back mechanisms, correlated with sympathetic hyperactivity. The symptoms may begin gradually and the disorder progresses in stages lasting from weeks to months. The management has not yet been established. Generally, the earlier the syndrome is recognized, the better the results of treatment will be. Analgesics, salmon calcitonin and physiokinesitherapy are recommended. Psychological support is advisable. In more severe patients sympathetic blockade and surgical sympathectomy may be necessary. The effects of hyperbaric oxygen treatment must still be assessed.
We report a case of a 73-year old railwayman with an asymptomatic large pericardial effusion diagnosed by a routine echocardiogram. By clinical and laboratory tests we excluded an immune, infectious, tuberculous and neoplastic origin of the pericardial effusion. A computed tomography scan of the thorax showed left pleural plaques. Pleural and pericardial biopsies showed fibrohyaline plaques and diffuse aspecific, chronic inflammation consistent with asbestos exposure. By using steroid treatment there was no further evidence of pericardial inflammation or pericardial effusion at 8 month follow-up. Steroid drugs are therefore suggested as a first choice treatment in patients with pleuropericardial effusion as well as chronic asbestos exposure.
Although the efficacy of intravenous thrombolysis in the treatment of acute myocardial infarction has been widely proved, some uncertainty concerning the "temporal window" of administration still persists. The aim of the present investigation was to study whether the late administration of a thrombolytic agent (6 or more hours after the onset of symptoms of acute myocardial infarction) offers any short or long-term advantages with regards to left ventricular function and clinical outcome. We studied 100 consecutive patients at their first episode of myocardial infarction, admitted to Coronary Unit within 24 hours of the onset of symptoms. Of these patients, 62 were administered rt-PA (44 patients within the 6th hour, and 18 between the 6th and 24th hour after the onset of symptoms) and the 38 remaining patients, who did not receive the thrombolytic agent (due to concerns with respect to possible complications), constituted the control group (18 admitted within 6 hours and 20 between 6 and 24 hours). All patients underwent serial electrocardiograms, and echocardiograms upon admission and at discharge to assess the ejection fraction, the asynergy score and the percentage of ischemic area. Furthermore, the survivors were invited for a follow-up examination one year after their acute initial episode. Seven cases of heart failure occurred, before discharge, among the control patients admitted 6 to 24 hours after onset of symptoms, compared with no cases in the subgroup of patients treated with rt-PA during the same time period (p = 0.0068).(ABSTRACT TRUNCATED AT 250 WORDS)
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We studied the proliferative activity and the modifications in ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, in the apparently normal intestinal mucosae of rats with azoxymethane induced tumours. Fifty rats were treated with six weekly injections of 15 mg/kg body weight azoxymethane (AOM). Six rats died during the treatment. All the surviving rats developed intestinal tumours; tumour incidence was 93.1% (41/44) in the left colon, 40.9% (18/44) in the right colon and 45.4% (20/44) in the small bowel. In the normal-appearing mucosa close to intestinal tumours we found an extension of the normal proliferative compartment to the upper third of the crypts (stage I abnormality) and a shift of most of the DNA synthesizing cells from the basal region to the middle and upper third (stage II abnormality). Furthermore, the intestinal mucosa characterized by proliferative abnormalities showed an ODC activity significantly higher than the normal mucosa of control rats (small bowel: 1.01 +/- 0.26 vs 0.42 +/- 0.15, P < 0.01; right colon: 1.32 +/- 0.34 vs 0.25 +/- 0.02, P < 0.001; left colon: 1.93 +/- 0.35 vs 0.22 +/- 0.01, P < 0.01). We also detected a significant decrease of DAO activity in the mucosa of the small bowel and right colon of treated rats compared to controls (0.86 +/- 0.09 vs 4.39 +/- 0.85, P < 0.01; 1.04 +/- 0.43 vs 3.80 +/- 0.91, P < 0.01, respectively), while DAO activity in the left colon was unchanged. The lower incidence of tumours in the small bowel and right colon suggests the presence of factors protecting these segments from carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
If the quality of results of organ transplantation in NITp is highly satisfactory, the same cannot be said for the number of transplants performed, which only cover 20-25% of the requirement. To understand the causes of organ shortage, a study group of Anaesthesiologists and Transplant Coordinators from the North Italy Transplant Program (NITp) investigated, through a questionnaire addressed to the Heads of 103 Intensive Care Units (ICU) in 92 Hospitals in the NITp area, some of the organizational problems linked to donor identification and treatment and to organ retrieval. The questionnaire took into consideration the number of possible donors identified in 1990, those retrieved and the causes for non retrieving organs and examined a number of variables linked both to retrieval and to ICUs and Hospitals organization. The results show that potential donors were 461: 143 (31%) were used, 138 (30%) were lost due to family opposition to organ donation, 192 (20%) for clinical reasons and 88 (19%) for organizational reasons. The latter figure represents 5% of non retrieval in the most active ICUs and increases to 50% in the Hospitals that had procured no donors in 1990. The main obstacles for ICUs to procure organ donors are: convey the Medical-Legal Committee, carry out of complicated administrative procedures, availability of round the clock specialized equipment for neurological assessment (especially for ICU outside Neurosurgical and Neurological departments), inadequate number of medical and nursing staff, most of all at night, and finally the difficulty in the management of non-traumatic cerebrovascular patients.
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