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Biomedical subjects

L Carnevali

Publications and source records attributed to L Carnevali.

At least 19 recordsLinked to original sources

Interferon-alpha in combination with ribavirin as initial treatment for hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis.

Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. In HCV-infected patients with MC, renal involvement worsens the overall prognosis because of a high incidence of infection or cardiovascular disease. The relationship between MC and HCV infection has prompted the use of antiviral therapy. Two patients with chronic HCV infection, type-II MC and membranoproliferative glomerulonephritis (MPGN), presenting as nephrotic syndrome were treated with interferon (IFN)-alpha (3 MU 3 times per week) and ribavirin (15 mg/kg daily) for 6 months. Laboratory tests included measurement of anti-HCV antibodies, HCV RNA, and HCV genotyping, and characterization of circulating cryoglobulins. A pretreatment renal biopsy was performed, and the histopathologic lesions were scored according to the index of disease activity. Viremia and cryoglobulinemia were suppressed in both patients. However, a complete remission of proteinuria was observed in 1 patient only. The evaluation of the renal biopsy specimens revealed a mild MPGN (activity score: 5/24) in the patient with remission of proteinuria and a severe MPGN (activity score: 15/24) in the patient who maintained a nephrotic-range proteinuria. Although a fully satisfactory treatment is not yet available, we feel that a reasonable therapeutic strategy for HCV-infected patients with MC nephritis could be as follows: (1) antiviral treatment alone for patients with a low-grade kidney involvement, and (2) a short-term course of steroids and cytotoxic drugs followed by antiviral therapy for acute exacerbations and/or rapidly progressive GN.

Adult↗

[Asymptomatic Chagas disease. Electrocardiographic and echocardiographic findings].

A total of 70 blood-donor volunteers were studied to determine the utility of the echocardiogram and Doppler in the diagnosis of cardiopathies in asymptomatic patients with Chagas disease. These patients came from endemic areas and had humoral positive reactions for South American Trypanosomiasis. They were checked against a control group of blood-donors with no environmental antecedents and with negative reactions. Both groups were similar in age and sex. The chagasic group showed an abnormal electrocardiogram in twelve cases (17.4%), being left anterior hemiblock the most frequent alteration found (nine cases, 62.5%). In the control group no alterations were found (p = 0.0005). The echocardiogram and Doppler were abnormal in 29 cases of the chagasic group (38.8%): alterations in ventricular relaxation were found in 8 cases (27.6%), enlargement of cavities in 9 (31%), both phenomena in 9 (31%) and alteration of parietal motility in 3 (10.3%). In the control group, 1 case presented alteration in ventricular relaxation (p = 0.000008). These results confirmed that the abnormal discoveries were related to Chagas disease. Out of 70 chagasic patients, 31 (44.29%) showed some alteration in the tests: 12 had an abnormal electrocardiogram, and of these only 2 had normal echocardiogram and Doppler, the rest showed abnormal echocardiogram and Doppler. Other 29 (of these 70 patients) showed some alteration in the echocardiogram and Doppler, and 20 of them presented a normal electrocardiogram. It can be concluded that the echocardiogram and Doppler are more accurate to detect cardiac involvement in asymptomatic chagasic patients than the electrocardiogram, showing abnormality in many cases where there are no electrocardiographic alterations. On the other hand, patients with abnormal electrocardiogram and Doppler are less frequent. Therefore, to define the undetermined period of Chagas disease echocardiogram and Doppler should be incorporated as a routine resource of diagnosis considering the high percentage of cases in which cardiac participation is detected when there is no clinic, radiologic and electrocardiographic disturbance.

Adult↗

Granular cell traumatic neuroma: a lesion occurring in mastectomy scars.

BACKGROUND: Granular cell changes can be observed in a variety of benign and malignant tumors, and are seen more commonly in granular cell tumors, which in about 5% of cases develop in the breast. Granular cells also have been observed in sites of previous trauma, such as surgery, and are found to be inflammatory reactions of histiocytic origin. METHODS AND RESULTS: We investigated, morphologically and immunohistochemically, 2 granular cell lesions occurring in mastectomy scars after surgery for carcinoma. Both lesions were composed of strands and nests of large granular cells, haphazardly set in a background of fibrous tissue, with sparse inflammatory infiltrates. Several tortuous hypertrophic nerve bundles were also embedded in the fibrous tissue. A few of these nerve bundles showed degenerative changes and contained granular cells. Immunohistochemically, granular cells were positive for S100 protein, neuron-specific enolase, vimentin, and CD68 antigen. CONCLUSIONS: We consider these proliferative lesions of peripheral nerves to have the features of both granular cell tumor and traumatic neuroma. These cases indicate that traumatic neuroma can undergo extensive granular cell changes and constitute a previously unrecognized entity, which we provisionally label granular cell traumatic neuroma. Granular cell traumatic neuroma has to be taken into consideration when evaluating lesions occurring at mastectomy scars and should be differentiated from malignant tumors with granular cells, such as apocrine carcinoma and alveolar soft part sarcoma.

Aged↗

p53 codon 72 polymorphism does not affect the risk of cervical cancer in patients from northern Italy.

A case-control study was performed to investigate the risk of cervical cancer associated with p53 polymorphism at codon 72, encoding either arginine or proline. It has been recently suggested that the arginine isoform increases the susceptibility to invasive cervical cancer; however, data remain controversial. The polymorphism was examined by both allele-specific PCR and RFLP analysis in 101 patients with primary cervical cancer and in 140 healthy women of the same age and from the same geographical area. The distribution of p53 genotypes in cervical cancer patients and in controls was not significantly different (P = 0.445), and homozygosity for arginine at residue 72 was not associated with an increased risk for cervical cancer (odds ratio, 0.81; 95% confidence interval, 0.47-1.42; P = 0.52). Similarly, different genotype distribution and increased risk were not observed when patients versus controls were analyzed according to human papillomavirus status and cancer histotype. Therefore, no evidence of association between homozygosity for p53 arginine and cervical cancer was found in our population sample.

Adult↗

Fluorescent in situ hybridisation on tissue sections: a quantitative approach with confocal laser scanning microscopy.

The use of fluorescent detection methods in association with digital microscopy technologies is an innovative approach for tissue localisation of messenger RNA. The success of such methods relies on the tissue preservation, local availability of the probe and on the existence of high resolution tridimensional analysis systems. Cryostatic sections, mild denaturation, short oligonucleotide probes (20mer) and confocal laser scanning microscopy allow the fulfillment of all these conditions avoiding photobleaching and tissue autofluorescence. In this paper, we describe in detail a method for in situ hybridisation set up with digoxigenin-coupled oligonucleotide complementary to beta-actin mRNA as a probe and an anti-hapten fluorescent antibody as second step for detecting specific hybridisation. Fluorescence was analysed by means of a confocal laser scanning microscope (CLSM) that provides images with low out-of-focus blurring also with relatively low numerical aperture (NA) objectives. We propose also an easy method to perform semi-quantitative thresholding analysis which allows to discriminate between background and specific signal.

Humans↗

Perinatal transmission of human papillomavirus from gravidas with latent infections.

OBJECTIVE: To evaluate the risk of perinatal human papillomavirus (HPV) transmission from mothers with latent infections to the oropharyngeal mucosae of their infants. METHODS: Seven hundred eleven mother-newborn pairs were tested. Polymerase chain reaction was done with MY09/MY11 consensus primers to identify HPV DNA in maternal cervicovaginal lavages and newborn nasopharyngeal aspirates. Positive cases were further amplified with type-specific primers for HPVs 6, 11, 16, 18, and 33. All infants born to HPV-positive mothers were observed to 18 months for appearance of HPV in oropharyngeal mucosae. RESULTS: Human papillomavirus DNA was detected in 11 neonates born vaginally to HPV-positive women, a vertical transmission rate was 30% (95% confidence interval [CI] 15.9, 47). Nasopharyngeal aspirates were HPV-negative in all 11 cases in which rupture of membranes occurred less than 2 hours before delivery. When rupture preceeded delivery by 2-4 hours, and when it occurred after more than 4 hours, the respective rates for HPV positivity were seven of 21 and four of five (chi2 for trend = 10.7, P = .001). At follow-up, virus was cleared from the oropharyngeal samples as early as the 5th week. CONCLUSION: Pregnant women with latent HPV infections have low potential of transmitting the virus to the oropharyngeal mucosae of their infants. The time between rupture of the amnion and delivery seems to be a critical factor in predicting transmission. Human papillomavirus-positive infants should be considered contaminated rather than infected since virus is cleared over several months after birth.

Adolescent↗

Neuroendocrine carcinoma of the skin with lymphoepithelioma-like features.

We report a case of primary neuroendocrine carcinoma of the skin (PNECS) mimicking a lymphoepithelioma-like carcinoma of the skin (LELCS) with respect to both cytomorphology and the presence of a dense lymphoplasmacytic stroma. The tumor occurred in the left forearm of a 86-year-old woman, and its history was marked by aggressive behavior, with metastases to lymph nodes and to visceral sites within 1.5 years of diagnosis. The neoplastic epithelial cells had an immunophenotypic profile typical of PNECS, reacting for cytokeratin 20 and other low-molecular weight cytokeratins, neuron-specific enolase, neurofilament protein, synaptophysin, and chromogranin A. In addition, they were immunoreactive for epithelial membrane antigen, carcinoembryonic antigen, and S-100 protein, as observed in LELCS of supposed adnexal differentiation. The tumor-infiltrating lymphocytes were mostly of T-lineage, with a predominance of CD8+ cells. We believe the case is a morphologic variant of PNECS, retaining its aggressive behavior and high metastatic potential, and should not be confused with true LELCS, which has a more favorable outcome. Immunohistochemistry is paramount in establishing the diagnosis. Lymphoid infiltration, even if prominent, does not seem to be of favorable prognostic significance in such a context.

Aged↗

Analysis and clinical implications of p53 gene mutations and human papillomavirus type 16 and 18 infection in primary adenocarcinoma of the uterine cervix.

Mutant p53 is frequently detected in endometrial and ovarian carcinoma, but it is rare in cervical cancers. Previous reports focused on cervical squamous cell carcinoma, whereas cervical adenocarcinoma was given little attention. We searched for p53 gene mutations in 74 primary cervical adenocarcinomas with known human papillomavirus (HPV) status. Our aim was to evaluate the prevalence of p53 mutations and to investigate their possible role as an independent prognostic factor. We found mutations in 13.5% with a high rate of G:C --> A:T transitions as observed in endometrial adenocarcinoma. As p53 mutations are more frequently detected in malignancies of high grade, high stage, and large size, this molecular event seems to play a role in the progression rather than in the induction of cervical adenocarcinoma. In our series, patients with HPV-negative tumors and patients with mutated neoplasms, irrespective of HPV infection, had a shorter survival. Yet the absence of HPV infection and presence of p53 mutations are not independent risk factors for tumor-related death after adjustment for clinicopathological confounders. The only significant and independent predictors of survival are age of patient, stage of disease, tumor grade, and presence of lymph node metastases.

Adenocarcinoma↗

Latent human papillomavirus infection in pregnant women at term: a case-control study.

Cervicovaginal lavages from 752 pregnant women at term were investigated by polymerase chain reaction to evaluate human papillomavirus (HPV) infection prevalences and were compared with cervicovaginal samples from two series of nonpregnant subjects (504 healthy women attending a family planning service and 560 symptomatic patients attending a vaginitis outpatient service). The odds ratios (ORs) of HPV infection were computed by conditional logistic regression analysis on age-matched sets. In pregnant women, the overall risk of HPV infection was about the same as in nonpregnant healthy subjects (adjusted OR, 0.90; 95% confidence interval [CI], 0.51-1.58) and was 50% less than in patients with symptomatic vaginitis (adjusted OR, 0.48; 95% CI, 0.30-0.76). Moreover, the prevalence of oncogenic HPV types 16 or 18 (or both) was lower in pregnant women (P = .015 and P = .0018 respectively).

Adolescent↗

p53 overexpression and human papillomavirus infection in transitional cell carcinoma of the urinary bladder: correlation with histological parameters.

Seventy-nine transitional cell carcinomas (TCCs) of the urinary bladder (25 grade 1, 22 grade 2, and 32 grade 3 tumours) were examined for p53 overexpression by immunohistochemistry with a monoclonal antibody and for human papillomavirus (HPV) infection by the polymerase chain reaction (PCR). Positive immunostaining for p53 was detected in 40.5 per cent of the cases; the percentage of positive cases was significantly lower in low-grade (G1 and G2) TCCs than in high-grade (G3) tumours (10.6 per cent vs. 84.4 per cent; P < 0.0001). The overall rate of HPV infection was 32.9 per cent; 20.3 per cent of the cases were positive for HPV 16, 3.8 per cent for HPV 18, and 8.9 per cent for both. Consensus primers as well as type-specific primers for HPV types 6, 11, and 33 failed to detect any additional case with HPV infection. The prevalence of HPV 16 and/or HPV 18 infection was significantly higher in low-grade than in high-grade tumours (44.7 per cent vs. 15.6 per cent; P = 0.0061). p53-positive cases were more common among papillary, deeply infiltrating tumours, and HPV-positive cases among papillary, non-infiltrating lesions. According to these data, p53 overexpression and HPV 16/18 infection are common findings in bladder TCC and there appears to be an inverse correlation of p53 overexpression and of HPV infection with tumour aggressiveness. The possibility of different molecular pathways in superficial low-grade and in invasive high-grade tumours is suggested.

Adult↗

Human papillomavirus types 16 and 18 infection in infiltrating adenocarcinoma of the cervix: PCR analysis of 138 cases and correlation with histologic type and grade.

The authors investigated by PCR 138 infiltrating cervical adenocarcinoma (27 grade 1, 76 grade 2, and 35 grade 3) for the presence of human papillomavirus (HPV) 16 and 18 infection. They included 95 (68.8%) mucinous and 43(31.2%) non-mucinous tumors. The overall prevalence of HPV infection was 84.8%; 28.3% of the cases were positive for HPV 16, 29.7% for HPV 18, and 26.8% for both HPVs. Amplification of HPV 16 and 18 negative cases with consensus primers MY09/MY11 failed to yield any additional tumors with HPV DNA sequences. Patients with HPV infection were younger than the patients who were HPV-negative (P = .001). The type of HPV was unrelated to age. Human papillomavirus infection was found in 95.8% mucinous and in 60.5% non-mucinous tumors (P < .001), with even distribution among grade 1, 2 and 3 adenocarcinoma. Our findings confirm the key role of HPV 16 and 18 in the development of cervical adenocarcinoma, particularly in mucinous histotypes. The absence of HPV infection, the old age of patients and the non-mucinous differentiation may identify a subset of cervical adenocarcinoma with different etiopathogenesis.

Adenocarcinoma↗

Analysis and clinical implications of K-ras gene mutations and infection with human papillomavirus types 16 and 18 in primary adenocarcinoma of the uterine cervix.

Experimental models indicate that activated ras genes and HPV oncogenic sequences may cooperate in inducing a completely transformed phenotype in epithelial cells. We searched for K-ras gene mutations and HPV type-16 and -18 sequences in 67 primary adenocarcinomas of the uterine cervix by analyzing DNAs from formalin-fixed, paraffin-embedded tissue samples. Target sequences were amplified by PCR and analyzed by denaturing gradient gel electrophoresis (DGGE) and sequencing for the detection of K-ras gene mutations and by Southern blotting for the detection of HPV infection. We found 16 mutations in 15 cases; 14 were at codon 12 and 2 at codon 13; 11 were base transitions and 5 were transversions. Mutations were more frequent in mucin-secreting than in non-mucinous tumors. HPV oncogenic sequences were detected in 58 cases with no significant difference between K-ras-mutated and wild-type tumors. HPV oncogenic sequences were also more frequent in mucin-secreting than in non-mucinous tumors. Both molecular events were present simultaneously in 13 out of 58 cases, all of which had histologically grade-2 and grade-3 tumors. Clinico-pathological parameters of the disease and the overall survival, however, were independent of K-ras mutations and of HPV-16 and -18 infection, as shown by univariate and multivariate analysis. In contrast, stage of disease, lymph-node metastases, deep infiltration, clear-cell histology and low grade of differentiation were risk factors for tumor-related death.

Adenocarcinoma↗

Acquired progressive lymphangioma of the skin following radiotherapy for breast carcinoma.

A case of a vascular tumor clinically and pathologically consistent with acquired progressive lymphangioma (benign lymphangioendothelioma) in a 48-year-old woman is reported. The lesion appeared in the skin close to a mastectomy scar 3 years after surgery and radiotherapy for invasive ductal carcinoma. On histologic examination, it mimicked an aggressive vascular neoplasm because of its infiltrative pattern. However, follow-up studies confirmed the benign nature of the lesion, clinically and histologically. This case indicates that acquired progressive lymphangioma may follow radiotherapy and must be considered in the differential diagnosis of other vascular proliferations occurring in the skin of the breast, especially of low-grade postradiation angiosarcoma, a recently described neoplastic entity.

Breast Neoplasms↗

Primary mucinous cystoadenocarcinoma of the retroperitoneum: two cases.

Two cases of primary retroperitoneal mucinous cystoadenocarcinoma of the ovarian type are reported. Both tumors occurred in females with bilateral normal ovaries and contained benign, borderline, and malignant mucinous epithelium. Full-thickness infiltration of the cyst wall was not found. In addition to surgery, one patient was given chemotherapy because of spillage from the tumor during intervention. There were no recurrences and no evidence of metastatic disease 19 and 33 months after diagnosis. Histologic findings suggest that the tumors had developed through mucinous metaplasia in preexisting mesothelial cysts.

Cystadenocarcinoma, Mucinous↗

Primary retroperitoneal mucinous cystoadenocarcinomas: an immunohistochemical and molecular study.

Special immunohistochemical stains for the identification of gastroenteropancreatic antigens in two cases of primary retroperitoneal mucinous cystoadenocarcinomas (PRMC) show that these tumours have patterns similar to ovarian mucinous tumours. Markers of pyloric type gastric mucosa differentiation (M1, cathepsin E, concavavalin A, pepsinogen II) are mostly positive in benign and borderline areas with endocervical type differentiation, while immunoreactivity for intestinal cell markers (M3SI and CAR-5) and for DU-PAN-2 is present mainly in frankly malignant areas, regardless of differentiation type. DNA analysis shows a point mutation of K-ras oncogene at codon 12 (GGT to CGT) in one case. The immunohistochemical and genotypic similarity of PRMC and ovarian mucinous tumours may indicate similar mechanisms in their histogenesis.

Antigens, Differentiation↗

Cervical adenocarcinomas express markers common to gastric, intestinal, and pancreatobiliary epithelial cells.

Frequency and pattern of expression of eight markers of gastric, intestinal, and pancreatobiliary duct epithelial cells have been investigated by histochemical and immunohistochemical techniques in 85 cases of cervical adenocarcinomas. M1, a mucin antigen, and Cathepsin E (CaE), an aspartic proteinase, markers of normal gastric superficial/foveolar epithelial cells, are expressed in 40 and 55 tumors, respectively. Periodic acid-concanavalin A-reactive mucin or Pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, are found in 24 tumors, 13 of which also express M1 and CaE. CAR-5 and M3SI, markers of intestinal mucin, are expressed in 68 and 12 tumors and DU-PAN-2, marker of normal pancreatobiliary duct cells, is found in 46 tumors. All but two tumors express at least one of the eight markers studied, none express PG I, marker of gastric chief cells. The different histologic subtypes of cervical adenocarcinomas expressed to a variable degree both gastrointestinal and pancreatobiliary markers. Only endocervical type tumors, however, showed the full spectrum of mucosal pyloric type differentiation, including the expression of PGII which is not present in any other histotype. A correlation between expression of gastroenteropancreatic markers and tumor grade is not apparent in our series.

Adenocarcinoma↗