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Biomedical subjects

N Pennelli

Publications and source records attributed to N Pennelli.

At least 19 recordsLinked to original sources

Relationship between apoptosis, tumour necrosis factor, and cell proliferation in chronic cholestasis.

BACKGROUND: Target of the immune response in chronic autoimmune cholestasis, is the bile duct epithelium. Lymphocytic infiltration and apoptosis have both been suggested to mediate the destruction of hepatocytes and biliary epithelium in primary biliary cirrhosis. AIMS: To further address this issue in two cholestatic liver diseases characterized by an autoimmune pathogenesis and, furthermore, evaluate the relationship between apoptosis and both tumour necrosis factor alpha and cell proliferation. METHODS: Liver tissue specimens from 16 patients with primary biliary cirrhosis, 15 with primary sclerosing cholangitis, and 16 with chronic hepatitis C (controls) were evaluated. DNA-fragmentation of apoptotic cells was ascertained by the TdT-mediated deoxyuridine triphosphate nick-end labelling method. Tumour necrosis factor alpha expression and cell proliferation (Ki-67 antigen) were assayed by immunohistochemistry. RESULTS: Hepatocytes with DNA fragmentation were observed in 75% of patients with primary biliary cirrhosis, in 66.6% with primary sclerosing cholangitis, and in 43.7% with chronic hepatitis C. Biliocytes showed apoptosis in only 3 cases of primary biliary cirrhosis. Biliocytes showed a strong cytoplasmic expression in 4 cases (1 primary biliary cirrhosis, 2 primary sclerosing cholangitis and 1 chronic hepatitis C). A few intralobular and portal inflammatory mononuclear cells expressing tumour necrosis factor alpha were observed in 62.5% of patients with primary biliary cirrhosis, 46.1% with primary sclerosing cholangitis, and 56.2% with hepatitis C virus chronic hepatitis. The amount of intraportal mononuclear cells expressing Ki-67 antigen was significantly higher in primary biliary cirrhosis specimens than in primary sclerosing cholangitis (p<0.001) or hepatitis C virus-related chronic hepatitis (p<0.03). No correlation was found within the 3 groups of patients between the Ki-67 histological score and the severity of liver disease. Moreover, no relationship was found between TdT-mediated deoxyuridine triphosphate nick-end labelling and either tumour necrosis factor alpha or Ki-67 staining. CONCLUSIONS: Apoptosis is a phenomenon which frequently involves hepatocytes in chronic autoimmune cholestasis. This process is apparently parallel, but unrelated to cell proliferation. Cell proliferation mainly involves mononuclear cells in portal tracts of primary biliary cirrhosis specimens. The finding of tumour necrosis factor alpha expression in biliocytes deserves further study to establish whether this cytokine is involved in triggering bile duct lesions.

Adult↗

Follicular dendritic cell tumor of the mediastinum.

Follicular dendritic cell tumor (FDT) is a rare neoplasm usually occurring in the laterocervical lymph nodes, but presentations elsewhere are also well documented. We report a case of FDT in a 48-year-old man with myasthenia gravis, in whom a slow-growing mediastinal mass that had been surgically excised manifested after 3 years with a local recurrence in the same site. The lesion was aspirated and cytology showed a tumor composed of groups of oval or elongated cells intermingled with several mature small lymphocytes. On histology, the tumor was highly cellular with abundant perivascular lymphocytic infiltration; large cells with pale, eosinophilic cytoplasm and round nuclei, arranged in fascicles often showed a storiform pattern. Occasional binucleated cells were also present. A panel of antibodies showed positivity only for CD21 and CD35, and a weak response to S-100. Electron microscopy showed that the layer cells had convoluted nuclei and elongated interdigitating processes with desmosome-like junctions. The definitive diagnosis of FDT can be concluded only with positive immunostaining for CD21 and CD35. However, in the presence of a mixed population of lymphocytes and larger eosinophilic cells the hypothesis of FDT should always be considered.

Biomarkers, Tumor↗

Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology.

Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed, paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S-phase, with aneuploidy and the highest proportions of S-phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is Confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.

Child↗

DNA flow cytometry of left and right testes in normospermic patients affected by left varicocele.

To assess whether changes in spermatogenesis are present in men suffering from varicocele who are still normospermic, a comparative flow cytometric analysis of the left and right testicular DNA content was performed on 26 young normospermic males (sperm density > 20 x 10(6)/ml), with varying degrees of asthenospermia. Cell samples were obtained by fine needle aspiration biopsy. Flow cytometric analysis revealed four peaks in the nuclear DNA content: (i) two peaks for haploid cells (1-A), the first composed of highly condensed nuclear cells (1Ac), essentially spermatozoa, and the second of less condensed cells, essentially spermatids (1-Anc): (ii) a third peak of diploid cells (2-D): somatic cells, G1-stage spermatogonia, primary and secondary spermatocytes and (iii) a fourth peak of tetraploid cells, essentially postleptotene primary spermatocytes and G2-M-stage spermatogonia (4-T). Flow cytometry showed the left testis to have a lower percentage of haploid cells than the right (mean 48.4 +/- 17.9 versus 57 +/- 15.4%, P < 0.05). Significantly fewer condensed cells were found on the left side than on the right (respectively 19.7 +/- 11.2 versus 31.5 +/- 13.5%, P < 0.004). The diploid cell percentage was significantly higher in the left testis than in the right (37.0 +/- 18.5 versus 25.5 +/- 9.6, P < 0.003). No statistically significant differences were found in respect of percentages of either non-condensed and tetraploid cells (respectively 26.6 +/- 14.8 and 11.3 +/- 5.6 on the left and 25.9 +/- 10.3 and 12.4 +/- 6.2 on the right). Flow cytometric analysis of cadaver biopsy tissue showed no statistically significant difference between left and right testicles in respect of the percentages of haploid, diploid and tetraploid cells. The reduced percentage of haploid cells and the increase in diploid cells observed in the left testis of our subjects indicate that the testicular function is impaired to a greater extent in the testis ipsilateral to varicocele than in the contralateral testicle.

Adult↗

CD25-negative hairy cell leukaemia: intracytoplasmic detection of Tac antigen and interferon-induced surface expression.

Hairy cell leukaemia (HCL) is a chronic lymphoproliferative disease of B-cell lineage. One of the peculiar immunophenotypic markers is the strong expression of the p55 chain of the interleukin-2 receptor (IL2R), recognized by anti-CD25 (or anti-Tac) monoclonal antibody. However, it is known that in rare cases CD25 may not be detectable, even when variant forms of HCL are excluded. The possibility has not been investigated that in these situations CD25 is present in the cytoplasm of the neoplastic cells. This paper describes a case in which the clinical, histological, and electron microscopic features were consistent with a typical HCL. Immunophenotype analysis showed the whole spectrum of markers of HCL, except for the expression of IL2R. The soluble form of the molecule was, however, increased in the patient's serum. Cytospin staining of the neoplastic B cells with anti-CD25 clearly demonstrated the presence of IL2R in the cytoplasm of hairy cells. When the cells were cultivated in vitro in the presence of interferon-alpha 2b, CD25 was detectable at the membrane level. These findings suggest that at least some cases of CD25-negative HCL may express cytoplasmic IL2R.

Aged↗

The extent of surgery for thyroid medullary cancer.

AIMS: Evaluation of the impact of the extent of primary surgery and reintervention on the outcome of patients with medullary thyroid carcinoma. METHODS: Seventy-two patients with medullary thyroid carcinoma (MTC) were surgically treated between 1967 and 1992. RESULTS: Fifty-five cases were sporadic, 5 patients had MEN 2A, 4 MEN 2B syndrome and 8 familial non-MEN MTC; 1 patient had stage I disease, 30 patients stage II, 36 stage III and 5 stage IV. Sixty-four had their initial treatment at our center, and 8 came for subsequent treatment. At first treatment, 8 patients were subjected to partial thyroidectomy, 10 to total thyroidectomy, 53 to total thyroidectomy with neck dissection, and 1 to only radical neck dissection; postoperative serum calcitonin (Ct) levels returned to normal in 3, 6 and 27 patients, respectively. In the patient with only radical neck dissection, Ct levels remained elevated. No patient with Ct normalization after surgery became responsive to pentagastrin in the follow-up. Thirteen patients had a reoperation due to nodal relapse. At a mean follow-up of 5.7 years (6-252 months), the 10-year survival rate was 84.5% with a significant difference between patients under and over 40 years of age (96.4 vs 57%), between stage I-II (100%) and stage III, IV (83.8%, 0% respectively). At the last follow-up, 36 (50%) patients were alive and disease free and 26 were alive with disease (15 with distant metastases). Of the 10 deaths, 7 were due to tumor recurrence, 3 to 120 months after surgery. CONCLUSIONS: Data suggest that an earlier diagnosis rather than more extensive surgery could improve survival and reduce recurrences. However, the least treatment required is total thyroidectomy plus central neck and upper mediastinum clearance and in addition, according to the extent of nodal involvement, mono- or bilateral neck dissection. To avoid ineffective reoperation due to distant (mainly liver) micrometastases, persistent residual microscopic disease requires a more aggressive restaging.

Carcinoma, Medullary↗

Fine-needle aspiration cytology of malignant nerve sheath tumors.

Precise preoperative diagnosis of three malignant nerve sheath tumors (MNST) was based on their remarkably uniform and highly characteristic cytologic appearance. The differential diagnosis with benign nerve sheath tumors and other spindle cell sarcomas is addressed, and the possibility of achieving confident diagnosis on cytologic material from at least some soft-tissue sarcomas is confirmed.

Aged↗

Simultaneous visualization of immunodetected antigens and tissue components revealed by non-enzymatic histochemical stains.

We explored the possibility of simultaneous application of histochemical and immunohistochemical staining techniques on the same paraffin-embedded human tissue section. Conventional histological stains (PAS, Alcian, Alcian-PAS, Van Gieson, Gomori silver impregnation, and Giemsa) were used in association with a battery of markers (keratins, leucocyte common antigen, S-100 protein, Factor VIII-related antigen) that are widely employed in diagnostic and experimental studies. We found that the best procedure was to perform immunostaining before the histochemical reaction, as this enables all the other possible combinations to be carried out. In addition, several detection systems, such as peroxidase-anti-peroxidase (PAP), alkaline phosphatase-anti-alkaline phosphatase (APAAP), and avidin-biotin complex (ABC), were tested and all gave consistent results. Some minor modifications of the histological staining methods were necessary, but the current immunohistochemical techniques could be used as established. Preliminary findings indicate that immunohistochemistry can be combined with histochemistry techniques by means of a relatively simple procedure whose only disadvantage is the time required to carry out the double staining.

Alkaline Phosphatase↗

First report of centroblastic lymphoma in a human immunodeficiency virus-positive patient with a rare congenital coagulation disorder (factor X Friuli).

The association of lymphoma and human immunodeficiency virus (HIV) seropositivity in a patient with a rare congenital clotting disorder (Factor X Friuli) is reported. The propositus was a previously asymptomatic HIV-positive 46-year-old man who suddenly presented a rapidly evolving right exophthalmos due to a centroblastic lymphoma, as the presenting symptom of full-blown AIDS. The clinical picture was characterized by unusual site of presentation, advanced stage and fatal course over a short period of time, despite therapy. Bone marrow, but not lymph node or parenchymal involvement, was present. Central nervous system involvement, with an unusual diffuse and massive pattern, and the B-cell origin of the lesion were demonstrated at autopsy. Few reports exist so far about the association of malignancy and HIV in patients with congenital coagulation disorders and this is the first report about a defect other than classic hemophilia.

Acquired Immunodeficiency Syndrome↗

Sudden death in young competitive athletes: clinicopathologic correlations in 22 cases.

PURPOSE: To investigate the pathologic substrates of sudden death in young competitive athletes. PATIENTS AND METHODS: Twenty-two cases of sudden death in young competitive athletes occurring in the Veneto region (northern Italy) in the period January 1979 to December 1989 were studied by postmortem examination. The athletes included 19 males and three females, ranging in age from 11 to 35 years (mean, 23 years). RESULTS: In 18 cases, sudden death occurred during (16 cases) or immediately after (two cases) a competitive sport activity. In 10 subjects, sudden death was apparently the first sign of disease. Postmortem examination disclosed that this fatality was due to arrhythmic cardiac arrest in 17 cases; among these, right ventricular cardiomyopathy, also known as "right ventricular dysplasia," was the most frequently encountered cardiovascular disease (six cases), followed by atherosclerotic coronary artery disease (four cases), conduction system pathology (three cases), anomalous origin of right coronary artery from the wrong aortic sinus (two cases), and mitral valve prolapse (two cases). In two athletes, the abrupt lethal complication was "mechanical" and consisted of pulmonary embolism and rupture of the aorta; in three athletes, death was due to a cerebral cause. All athletes with right ventricular cardiomyopathy died during effort, and most had a history of palpitations and/or syncope. Whenever available, electrocardiographic (ECG) tracings showed inverted T waves in precordial leads and/or left bundle branch block ventricular arrhythmias. CONCLUSIONS: Clinicopathologic correlations indicate that in the Veneto region of Italy, right ventricular cardiomyopathy is not so rare among the cardiovascular diseases associated with the risk of arrhythmic cardiac arrest, and seems to account for the majority of cases of sudden death in young athletes; this disorder can be suspected during life on the basis of prodromal symptoms and ECG signs.

Adolescent↗

[Spontaneous dissecting coronary hematoma (aneurysm) and sudden death].

Two women, 34 and 54 years old, died suddenly from acute coronary occlusion due to spontaneous dissecting haematoma (aneurysm) involving the entire left coronary artery and the right coronary artery, respectively. In the older woman, cystic medial necrosis of the coronary tunica media was observed. The younger case was the only sudden death due to dissecting hematoma among 120 cases in the Registry of "juvenile sudden death" in the Veneto Region, Italy. From a review of the literature, following the first description in 1931, we collected 97 cases with the following characteristics: mean age in women, 39 years, in men, 48 years; only significant risk factor: peripartum (34% of women); coronary arteries involved: isolated left anterior descending (52.5%, equally distributed among women and men), right (24%, mainly men), left (13.5%, only women), multiple vessels (8%), left circumflex artery (2%). The clinical presentation was cardiac arrest with sudden death in 49.5%, acute, non-fatal myocardial infarct in 33%, and acute fatal myocardial infarct in 17.5% of the cases. The prognosis is very poor, and emergency medical or surgical myocardial revascularization is rarely feasible.

Adult↗

Right ventricular cardiomyopathy and sudden death in young people.

From 1979 to 1986, we conducted postmortem studies of 60 persons under 35 years of age who had died suddenly in the Veneto Region of northeastern Italy. Unexpectedly, we found that 12 subjects--7 males and 5 females ranging in age from 13 to 30 years--had morphologic features of right ventricular cardiomyopathy. This disorder had not been diagnosed or suspected before the subjects died. In five cases, sudden death was the first sign of disease; the remaining seven subjects had a history of palpitation, syncopal episodes, or both, and in five of those seven, ventricular arrhythmias had previously been recorded on electrocardiographic examination. Ten of the subjects had died during exertion. At autopsy, the subjects' heart weights were normal or moderately increased. Two main histologic patterns were identified--a lipomatous transformation or a fibrolipomatous transformation of the right ventricular free wall (6 cases each); in all cases, the left ventricle was substantially spared. Signs of myocardial degeneration and necrosis, with or without inflammatory infiltrates, were occasionally observed. These findings indicate that right ventricular cardiomyopathy, the cause of which is still unknown, may be more frequent than previously thought. At least in this area of Italy, it may represent an important cause of sudden death among young people.

Adolescent↗

Sudden death as the first manifestation of coronary artery disease in young people (less than or equal to 35 years).

During 1979 to 1987, we collected 84 consecutive cases of juvenile sudden death which occurred in the Veneto Region, northeast Italy. Death was attributed to cardiovascular disease in 79 cases. Nineteen of these (24%), consisting of 17 males and two females, from 18 to 35 years of age, had 70% or greater atherosclerotic coronary stenosis, in the absence of other cardiac pathology and previous clinical evidence of angina pectoris or myocardial infarction. In 13 cases (68%), sudden death was the first manifestation of coronary artery disease; the remaining six patients had experienced atypical, non-diagnostic prodromal symptoms. At the moment of death, 16 patients were engaged in sedentary activity. Pathological examination disclosed that in 15 cases (79%), only one major vessel was stenosed, and in 12 cases it was the proximal descending coronary artery: the other four patients had three-vessel disease. Histologic study revealed uncomplicated, obstructive fibromatous plaques in 16 cases, and a preserved tunica media in all cases. Plaque fissuring with superimposed mural or occlusive thrombosis was present in only three cases. Overt myocardial infarction was not observed. Our findings indicate that coronary atherosclerosis is an important cause of sudden death in young persons. In this series, coronary disease was 'silent', and sudden death was its first clinical manifestation. The occurrence of death at rest, in the absence of an acute coronary lesion, with preservation of the coronary tunica media suggests that fatal outcome might be due to coronary vasomotor tone abnormalities culminating in ischaemia-induced cardiac arrest.

Adolescent↗

Long-term survival in response to combined chemotherapy and radiotherapy in laryngeal small cell carcinoma.

Fourteen patients with small cell carcinoma of the larynx are studied. This represents the largest series, from a single institution, reported in the literature. This neoplasm is usually highly aggressive and the prognosis very poor, but, in our experience, combined chemo- and radiotherapy can significantly improve the clinical course of the disease. Three of six patients who received this combined modality treatment are still clinically disease-free more than six years after the initial diagnosis.

Aged↗

Mucoid carcinoma of the breast on fine-needle aspiration biopsy sample: cytology and ultrastructure.

16 cases of mucoid carcinoma of the breast were diagnosed in specimens obtained by fine-needle aspiration biopsy. The subsequent tissue examination confirmed the cytologic diagnosis in all 16 cases but revealed in 1 case an association with an endocrine component and in 3 cases the presence of an invasive ductal component. The diagnostic and prognostic necessity of distinguishing pure forms of mucoid carcinoma from those associated with invasive ductal carcinoma or endocrine differentiation means that investigations other than fine-needle aspiration biopsy are also required. In every case, the cytologic diagnosis of mucoid carcinoma should be considered as an aspect of the tumor and not representative of the entire neoplasm.

Adenocarcinoma, Mucinous↗