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Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 325 records · Page 18Linked to original sources

PRINS localization of centromeres and telomeres in micronuclei indicates that in mouse splenocytes chromatid non-disjunction is a major mechanism of aneuploidy.

Primed In Situ DNA Synthesis (PRINS) of telomeric and centromeric (minor satellite DNA) sequences has been applied together with the cytokinesis block micronucleus (MN) assay in mouse splenocytes, with the aim of understanding the mechanism of origin of spontaneous and induced MN. Splenocyte cultures were treated in vitro either with the clastogenic agent mitomycin C or with the aneugenic compound colcemid. The relative proportions of MN carrying 1 to 4 telomeric signals were in agreement with the known mechanism of action of the chemicals tested, i.e., an higher number of MN with less than 4 telomeres were found in MMC-than in colcemid-treated cultures. No MN lacking the telomeric sequences (0 spot) were found, indicating that the observed distributions should not be affected by false-negative data. Furthermore, all MN carrying a single telomere were negative for the centromere, thus indicating that this class represents true chromosome acentric fragments. Finally, MN with 4 telomeric spots always carried the centromeric sequence, as expected on the hypothesis that these MN correspond to whole chromosomes. With respect to centromere-positive MN, more than one half carried 4 telomeric signals (whole chromosomes), and only 1/4 or less showed 2 telomeric signals (probably corresponding to a single chromatid). This difference was statistically significant, either in untreated cultures or in cultures exposed to mitomycin C or colcemid. On the whole, these data indicate that non-disjunction followed by whole chromosome loss (with the production of two daughter monosomic nuclei) may be the main mechanism of malsegregation leading to MN formation.

Aneuploidy↗

Vestibular schwannoma and the only hearing ear.

With the recent advances in the management of vestibular schwannomas, it is possible not only to save the facial nerve function but also preserve hearing in a small percentage of cases. Difficulties arise while managing patients with vestibular schwannoma in their only hearing ear. In this article we summarize our experience in managing seven of these patients. We recommended a watch and wait policy with a regular follow-up with audiometric testing and gadolinium-enhanced magnetic resonance imaging (MRI). Gamma knife radiosurgery is advised in cases with deterioration of hearing or increase in tumour size. Surgery is usually avoided unless there are brainstem compression symptoms.

Adult↗

Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis.

The prognostic weight of histological and biological factors was compared with that of known clinical prognostic factors in a population of 108 consecutive previously untreated patients with head and neck squamous cell carcinoma. Parameters studied were: tumour vascularisation, mitotic index, histological differentiation, nuclear grade, keratinisation, desmoplasia, growth pattern, inflammation, tumour emboli in peripheral vessels, keratins 6, 13, 19 immunohistochemical expression, cytofluorometric ploidy and S-phase. In multivariate analysis (Cox), only age and nodal status had a significant impact on the overall survival, whereas T stage was the only significant factor associated with locoregional failure. The cumulative incidence of metastases was correlated not only with age, T and N stage, but also with histological differentiation. All the other histological and biological factors studied failed to provide further prognostic information. These findings may help to select patients with high metastatic risk.

Age Factors↗

A single unit of transfused allogeneic blood increases postoperative infections.

The aim of this prospective study was to evaluate if there was a statistical correlation between allogeneic blood transfusion and postoperative infections, and if this could have a dose-dependent pattern. The evaluation was based on multiple logistic and receiver operating characteristics (ROC) curve analyses. On hospital admission the following parameters were determined in 267 consecutive patients with colorectal cancer: hemoglobin, serum albumin, serum cholinesterase activity, total iron binding capacity and weight loss. Duration of operation, operative blood loss, amount of transfused blood, Dukes' cancer stage and occurrence of postoperative infections were also recorded. One hundred and thirty-two patients (49.4%) were given perioperatively allogeneic blood. Postoperative infections developed in 47 (17.6%) patients. Multivariate analysis identified allogeneic blood transfusion as the only variable related to the occurrence of postoperative infections (p < 0.05). ROC curve analysis showed that the risk for the occurrence of infection was significantly higher in patients transfused one unit of blood (p < 0.01). Moreover, a significant trend between increasing number of transfused blood units and susceptibility to infection was found (p < 0.00019).

Bacterial Infections↗

Genotoxicity of trophosphamide in mouse germ cells: assessment of micronuclei in spermatids and chromosome aberrations in one-cell zygotes.

The genotoxicity of trophosphamide (TP) in mouse germ cells was assessed by the cytogenetic analysis of micronuclei in spermatids and chromosome aberrations in one-cell zygotes and compared with the genotoxicity in somatic cells evaluated by the micronucleus reticulocyte assay. Single acute doses of 50, 75, 100 and 150 mg/kg were studied after i.p. injection. TP was only weakly mutagenic for preleptotene spermatocytes-differentiating spermatogonia, but clear-cut cytotoxic effects were demonstrated after treatment of these cells by a dose-dependent reduction of the ratio between Golgi and cap phase spermatids. Effects induced in post-meiotic stages were estimated, after mating the treated males with untreated superovulated females, by the frequencies of zygotes with chromosome aberrations: a peak of genetic damage was detected in late spermatids, with as many as 55% zygotes with aberrations, but spermatozoa and early spermatids were also clearly affected. When compared with matched solvent-injected controls, the lowest effective dose in spermatozoa and late spermatids was 100 mg/kg, although the 3- to 4-fold increases detected at 50 mg/kg were also statistically significant when compared with a pool of laboratory controls. In peripheral blood reticulocytes, the micronucleus frequencies were increased by 3-20 times the respective baseline values in the individual animals. A marked cytotoxic effect on bone marrow cells was revealed by the reduction of the proportion of early reticulocyte stages, which dropped to 20% of the control value at 150 mg/kg. Both genotoxic and cytotoxic effects were higher in bone marrow than in germ cells of the same animals, pointing to a generalized higher susceptibility of somatic cells to TP, possibly related to chemical distribution and target organ accessibility. The accurate description of stage- and dose-effect relationships in germ cells of experimental models is crucial for genetic risk assessment after chemical exposure. The approaches applied in this study may contribute to this goal.

Animals↗

The centromere as a target for the induction of chromosome damage in resting and proliferating mammalian cells: assessment of mitomycin C-induced genetic damage at kinetochores and centromeres by a micronucleus test in mouse splenocytes.

The cytokinesis-block micronucleus assay (MN) on murine splenocytes was used for the estimation of chromosome damage in a resting cell population in vivo that can be induced to proliferate in vitro. Mitomycin C at different doses (10(-8), 6 x 10(-8), 10(-7), 6 x 10(-7) and 10(-6)M) was used to induce cytogenetic damage in resting and cycling splenocytes. Antikinetochore antibodies (CREST) and two-colour fluorescence in situ hybridization (FISH) with minor and major satellite DNA were applied. These approaches allowed the detailed characterization of the mechanisms by which MN originates, since it was possible to identify breaks induced in pericentric heterochromatic (resulting in MN containing the major but not the minor satellite DNA) or detachment/disruption of kinetochore (resulting in different frequencies of MN containing kinetochore or both probes). Based on the evidence that resting and cycling mouse splenocytes are characterized by different spatial distribution of centromeric regions, the hypothesis was tested that the damage induced by mutagens at centromeres is influenced by the phase of the cell cycle in which the cells are treated. Data presented here show that resting and cycling splenocytes are both sensitive to mitomycin C action, and indicate that this compound has an aneugenic potential, besides its strong clastogenic activity. In particular, results obtained after CREST and FISH characterization of MN differed when cells were treated during proliferation, suggesting a disruption/detachment of kinetochores induced by mitomycin C at this cell stage. Furthermore, under the same treatment condition the proportion of MN containing the major satellite DNA only was greater than expected on the basis of random breakage at this site. Treatment of resting cells produced aneugenic damage, but without evidence of disruption/detachment of kinetochores or preferential breakage at the centromere. These results indicate that the amount and type of chromosome damage induced by mitomycin C in mouse splenocytes differ in relation to the proliferative status of treated cells.

Animals↗

Detection of minor and major satellite DNA in cytokinesis-blocked mouse splenocytes by a PRINS tandem labelling approach.

A protocol for the simultaneous visualization of minor and major satellite DNA by primed in situ DNA synthesis (PRINS) was developed in cytokinesis-blocked murine splenocytes. After individuation of optimal experimental conditions, a micronucleus (MN) test was carried out by treating splenocytes in vitro with the clastogenic agent mitomycin C and the aneugenic compound Colcemid. It was found that PRINS gives highly reproducible results, also comparable with the literature on MN results obtained by fluorescent in situ hybridization (FISH). Therefore the PRINS methodology may be proposed as a fast alternative to FISH for the characterization of induced MN.

Animals↗

Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. The "Gruppo Oncologico Centro-Sud-Isole' (G.O.C.S.I.).

PURPOSE: To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer. PATIENTS AND METHODS: 204 patients were entered in a phase III multicentre randomised trial from June 1990 to December 1994 and stratified according to the ECOG performance status (0-1 vs. 2). MVP was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/m2+cisplatin 100 mg/m2 i.v. day 1 and vindesine 3 mg/m2 i.v. day 8 with cycles repeated every 4 weeks. MEV was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/ m2 i.v. day 1 and etoposide 100 mg/m2 i.v. days 1 to 3 with cycles repeated every 3 weeks. For both treatments a maximum of 6 cycles was planned. Response and toxicity were evaluated according to WHO. Subjective responses were assessed by numerical scales. Analyses were made on the basis of intent to treat. RESULTS: The objective response rate was 21.4% (1 CR + 21 PR among 103 patients) in the MEV and 28.7% (1 CR + 28 PR among 101 patients) in the MVP arm (P = 0.48). Symptoms were similar in the two arms. 196 patients progressed and 182 died. The median times to progression were 10 weeks (95% CI 9-12) and 12 weeks (95% CI 10-15) and median survivals were 29 weeks (95% CI 25-36) and 28 weeks (95% CI 25-35) in the MEV and MVP arms, respectively. The relative risks of progressing and of dying were 0.89 (95% CL 0.66-1.20) and 0.96 (95% CL 0.71-1.30), respectively, for patients receiving MVP as compared with those receiving MEV at multivariate analysis adjusted by sex, age, histologic type, number of metastatic sites, performance status at entry, and centre. CONCLUSIONS: In the present study, no significant differences were observed in response rate, survival or palliation of symptoms between the MEV and MVP regimens, while toxicity was significantly more frequent and severe with MVP. Thus, MEV should be considered a reasonable alternative to the MVP regimen in the treatment of stage IV NSCLC.

Adult↗

Lack of association between type of hepatitis C virus, serum load and severity of liver disease.

Chronic infection with the hepatitis C virus (HCV) may lead to a variety of hepatic lesions from benign inflammation to liver cancer, but the relationships between infection and development of liver disease are poorly understood. To assess whether virus type and load are of pathogenetic importance, 197 Italian carriers with various hepatic lesions were investigated consecutively. Of these, 187 (95%) patients had serum HCV RNA, by reverse transcription-polymerase chain reaction (RT-PCR) with a median level of 1003 x 10(3) genomic equivalents ml-1 according to the branched-DNA assay (b-DNA). One hundred and seven patients (54%) had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed serotypes and 42 (21%) had no specified serotype. One hundred and thirty four patients were also tested for genotype. The genotype distribution was as follows: 17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4 and 1 (1%) had mixed genotype 1a + 3a. No virus type was associated with any particular histological diagnosis and all were equally distributed between progressive and non-progressive liver disease groups. Serum HCV-RNA levels were similar in the liver diseased groups. By analogy to hepatitis B, there was no direct correlation between type and level of viraemia and the severity of the underlying liver damage.

Adult↗

Effects of mediastinal irradiation on oesophageal function.

Although it is well recognised that oesophageal symptoms are common during therapeutic mediastinal irradiation of intrathoracic malignant diseases, the effects of mediastinal irradiation on oesophageal function are poorly defined. To clarify the pathogenesis of these sequelae a prospective study was performed to document comprehensively the effects of mediastinal irradiation on oesophageal function. Oesophageal symptoms, barium swallow, endoscopy, and combined radionuclide scintigraphy and oesophageal manometry were evaluated in eight patients with potentially curable intrathoracic malignant disease before treatment, during the last week of mediastinal irradiation, and six to eight weeks after its completion. Before irradiation, structural abnormalities were excluded by barium swallow and endoscopy. All but one patient experienced odynophagia or dysphagia, or both, during mediastinal irradiation (p < 0.001) but endoscopic abnormalities were observed in only three patients and there was no correlation between oesophageal symptoms and endoscopic changes. Irradiation, however, had no significant effect on oesophageal motility or transit. It is concluded that oesophageal symptoms which develop during mediastinal irradiation are not a result of altered oesophageal motility or transit and may reflect increased mucosal sensitivity.

Aged↗

Hyperglycemia affects cardiovascular autonomic nerve function in normal subjects.

OBJECTIVE: To evaluate the effect of acute hyperglycemia on autonomic nerve function in normal subjects. RESEARCH DESIGN AND METHODS: Six healthy volunteers ages 19-32 years underwent paired studies during euglycemia (blood glucose 5.1 +/- 0.04 mmol/l) and hyperglycemia (blood glucose 15.7 +/- 0.48 mmol/l) induced by intravenous infusion of glucose and maintained for 150 min. The order of the two studies was randomized. In each experiment, supine heart rate, heart rate variation with respiration, ratio of the maximum to minimum R-R interval after standing ("30:15" ratio), systolic blood pressure response to standing, and diastolic blood pressure response to sustained handgrip were measured. Data were analyzed using repeated measures analysis of variance. RESULTS: The supine heart rate was greater (P = 0.04) and the "30:15" ratio less (P = 0.03) during hyperglycemia than during euglycemia. Hyperglycemia had no significant effect on any of the other cardiovascular reflex tests. CONCLUSIONS: These observations indicate that acute hyperglycemia affects autonomic nerve function in healthy humans.

Adult↗

Pleomorphic adenoma and adenoid-cystic carcinoma of salivary glands: immunohistochemical assessment of proliferative activity in comparison with flow-cytometric study.

In this study, 32 pleomorphic adenomas (PAs) and seven adenoid cystic carcinomas (ACCs) were analysed for the evaluation of proliferating cell nuclear antigen (PCNA) indices and flow cytometric variables. Our aim was to assess any possible relationship between these parameters and the clinico-pathological variables and to clarify their histogenesis and reasons for their biological differences. The tumours were divided into three groups, mainly epithelial (E), myxoid (M) and chondroid (C); PCNA labelling index (LI) and weighted mean index (WI) and the WI/LI ratio were analysed in the predominant components; a single PCNA index, weighted by the percentage of each component, was also calculated. Only WI/LI was found to be significantly different in the three components, while PCNA single index did not show either significant differences by sex, age, site and size, or any correlation with the S phase fraction. A significant difference was found between PAs and ACCs by site (P < 0.01) and DNA ploidy (P < 0.05); furthermore, all PCNA indices (single index) were significantly lower in PAs than in ACCs.

Adenoma, Pleomorphic↗

Congenital cholesteatomas of the middle ear: a different experience.

A retrospective analysis is presented of 44 cases of congenital cholesteatoma of the middle ear. Twenty-one patients had cholesteatoma localized to the posterosuperior mesotympanum in complete contrast to the commonly reported anterosuperior location seen in only two cases. The remaining 21 patients had cholesteatoma involving either the entire mesotympanum or epitympanum or both. The posteriorly located congenital cholesteatomas might represent a completely different entity and originate from the trapped epithelial cell rests in the posterior mesotympanum during the development of temporal bone. All but one patient were treated by using a closed tympanoplasty. Eight patients underwent a single-stage surgery. A preplanned second-stage procedure was performed in 33 patients, and three are awaiting their second stage. Residual disease was seen in 19 (57%) patients undergoing second-stage surgery. No patient has had recurrent disease so far. Thirty-eight (85%) patients had a preoperative air-bone gap of > or = 30 dB. Of the 33 patients considered for hearing results, 16 (48%) had a postoperative gap within 10 db.

Adolescent↗

[Vestibular neurectomy by retrolabyrinthine approach in cases of untreatable Meniere's disease].

We report on a series of 35 Ménière's disease patients, all of whom had undergone retrolabyrinthine vestibular neurectomy between 1987-1993. The overall success rate of vertigo relief was 96.7% with no serious or permanent complications resulting from the procedure. The current literature is reviewed and our results are compared with those of previous reports. The technical elements of the operation, regarding our approach and those of the others are analyzed with special attention given to the anatomical features of the region and their influence on success or failure. We conclude that the retrolabyrinthine approach for nerve section remains a safe and highly successful technique which continues to be widely used.

Adult↗

[Doppler flow-velocity analysis of the renal arteries in left ventricular dysfunction].

AIM OF THE STUDY: Chronic heart failure leads to renal hypoperfusion. Clinical methods for monitoring renal artery flow have several limitations. We analyzed the renal artery flow-velocity in patients with left ventricular dysfunction and normal controls by pulsed-wave (PW) color-guided Doppler technique. The relation between PW Doppler quantitative indexes and left ventricular ejection fraction (LVEF), creatinine clearance, and age, was also assessed. METHODS: We studied 53 patients with left ventricular dysfunction (LVEF by 2D echo < or = 40%) and no systemic hypertension, diabetes, parenchymal nephropathy, serum creatinine levels > 150 mmol/l, nor renal artery stenosis. Five patients were excluded for suboptimal renal artery PW Doppler recordings. Thus, the study group was constituted of 48 patients (mean age: 64 +/- 13 years). Twenty-eight normal subjects (mean age: 61 +/- 9 years) were the control group. By PW Doppler we measured the maximum (Vmax), the minimum (Vmin) and the mean (Vmean) velocities of both renal arteries. The resistivity index (RI), obtained from the formula (Vmax-Vmin)/ Vmax, and the pulsatility index (PI), obtained from the formula (Vmax-Vmin)/Vmed were calculated. Creatinine clearance was determined in each patient. RESULTS: RI and PI were greater in patients with left ventricular dysfunction than in normal controls. In normal controls, RI and PI were related to age (r: 0.63, p < 0.001; and r: 0.45, p < 0.05) and creatinine clearance (r: -0.44 and -0.40, respectively; both: p < 0.05), not to LVEF. In patients with left ventricular dysfunction, RI and PI were related to LVEF (r: -0.67 and -0.59; both: p < 0.001), other than to age (r: 0.57 and 0.55; both: p < 0.001) and creatinine clearance (r: -0.59, p < 0.001, and r = -0.46, p < 0.01, respectively). In this group, however, there was no sharp separation of RI and PI between patients with different degree of left ventricular dysfunction (LVEF < or = 30% and > 30%). CONCLUSIONS: In patients with left ventricular dysfunction, by renal artery PW Doppler analysis it is possible to detect noninvasively a reduction in regional flow-velocity and an increase in Doppler-derived vascular resistance indexes. These Doppler changes mainly depend on severity of left ventricular dysfunction and less on age of patients.

Adult↗

The epidemiology of esophageal cancer.

The present paper examines the epidemiological aspects of cancers of the esophagus. Esophageal cancer is the sixth most common cancer in the world. Large geographical and temporal variations in its incidence, even within small areas, suggest that environmental exposure is causally important. Smoking and alcohol consumption are major risk factors for esophageal cancer, and alcohol has been identified as a major cause of this neoplasm in industrialised countries. In addition to smoking and alcohol consumption, dietary habits are important risk determinants of this disease. Epidemiological evidence suggests that nutritional deficiencies and, possibly, ingestion of mycotoxins and nitrosamines are factors for the development of esophageal cancer.

Alcohol Drinking↗

[Mepartricin in BPH. A new dosage approach].

The authors assessed the validity of a treatment with mepartricin in BPH at the dose of 150,000 U in a once-a-day evening administration for 6 months. The results from the controlled study were compared with those obtained in a homogeneous group of patients treated with placebo. The analysis of the data obtained would suggest a preferential opinion in favour of the group treated with mepartricin which was effective in improving the symptomatology. Some hypothesis are put forward to interpret the results.

Aged↗