PubMed Health⌕ Search

Biomedical subjects

A Marchetti

Publications and source records attributed to A Marchetti.

At least 73 records · Page 4Linked to original sources
PubMed1995

Detection of DNA mutations in acid formalin-fixed paraffin-embedded archival tumor specimens by polymerase chain reaction-single strand conformation polymorphism analysis.

A single strand conformation polymorphism analysis on polymerase chain reaction (PCR)-amplified genomic DNA was used for the detection of DNA mutations in acid formalin-fixed, paraffin-embedded tissues. Fifty non-small cell lung cancers were screened for mutations in the exon 5 of the p53 tumor suppressor gene. Structural abnormalities of the gene were found in nine (18%) of the tumors examined. The results show that paraffin-embedded tissues fixed in unbuffered formalin can be a good source of DNA for a mobility shift analysis by neutral polyacrylamide gel electrophoresis. The described procedure allows retrospective genetic studies on paraffin blocks available in all pathology departments.

Base Sequence↗
PubMed1994

In-vitro and in-vivo activity of rifabutin against Toxoplasma gondii.

The activity of rifabutin against Toxoplasma gondii was investigated in vitro and in vivo. One set of in-vitro studies used either a low virulence or a high virulence T. gondii strain subcultured in drug-free conditions after exposure to various drug concentrations. No parasite growth was observed after subculture at 1 month after exposure to 6 mg/L of rifabutin for the low virulence and 12 mg/L for the high virulence strain. The IC50 of rifabutin was 26.5 mg/L in a different series of experiments using an enzyme-linked immunoassay) and the T. gondii high virulence strain. In similar experiments with clarithromycin, low virulence and high virulence parasites grew in drug-free subcultures following exposure to drug concentrations as high as 100 mg/L; the IC50 of clarithromycin exceeded 100 mg/L for the high virulence strain. In the acute toxoplasmosis murine model, mice received a 12 day treatment starting 5 days before infection with high virulence parasites. Survival was significantly improved compared with untreated controls in response to 50, 100 and 200 mg/kg/day rifabutin and 100 and 200 (but not 50) mg/kg/day clarithromycin, and with the combination of the two drugs at 25, 50 and 100 mg/kg/day. Survival was significantly improved when combination therapy was administered. The calculated ED50 values (mg/kg/day) were 160.5 for rifabutin, 119.4 for clarithromycin, and 114.8 for the combination. In the present experimental conditions rifabutin proved effective in vitro and in vivo against T. gondii and showed potentiation with clarithromycin in vivo.

Animals↗
PubMed1993

p53 mutations and histological type of invasive breast carcinoma.

A polymerase chain reaction-single strand conformation polymorphism assay was used to assess p53 mutations in 148 invasive breast carcinomas, selected on the basis of their histotype. They comprised 56 lobular, 47 ductal, 19 mucinous, 18 medullary, and 8 papillary carcinomas. The distribution of p53 mutations was significantly different (P = 0.006) in the histotypes examined: mutations were frequent in medullary (39%) and ductal (26%), less common in lobular (12%), and absent in mucinous and papillary carcinomas. The frequency of mutations in the exon 5 of the p53 gene was significantly higher in medullary carcinomas than in the other histotypes: 5 (63%) of the mutations found in exon 5 were observed in medullary carcinomas (P = 0.012). One hundred twenty-two tumors from the total were also examined by immunohistochemistry for p53 overexpression using antibody PAb 1801. A specific immunostaining in neoplastic cells was present in 12 tumors. A strong correlation (P < 0.001) was observed between p53 mutations and nuclear accumulation of the p53 protein: 10 tumors were scored positive for both p53 mutation and overexpression. However, in 9 cases having a mutated p53 gene we failed to find a positive immunoreaction. A significant association (P = 0.01) was present between mutations in the p53 gene and high proliferative activity of the tumors determined by immunohistochemistry with monoclonal antibody Ki-67. Moreover, a significantly higher expression of the Ki-67 antigen was found in medullary carcinomas compared to the other histotypes. Our findings indicate that in invasive breast carcinomas structural abnormalities of the p53 gene are mainly seen in medullary and ductal tumors and that the other histological types, especially those associated with a high level of differentiation and favorable prognosis, show a very low incidence of p53 mutations.

Base Sequence↗
PubMed1993

p53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes.

Alterations of p53 are one of the most common molecular changes found in all types of lung tumors, suggesting a crucial role for p53 in bronchial carcinogenesis. However, the prognostic significance of p53 abnormalities in lung cancer patients is still unclear. By using genetic and immunohistochemical methods we have found p53 alterations in 40 of 53 (75%) primary, resected non-small cell lung cancer. A strong association (P = 0.0015) was found between deletions on chromosome region 17p13.3 and p53 mutations suggesting that loss of the wild-type p53 allele might be necessary for tumorigenesis. Correlations to clinicopathological parameters showed that p53 alterations (structural aberration of the gene and/or nuclear accumulation of the protein) are significantly linked with metastatic involvement of hilar and mediastinal lymph nodes (P < 0.01). Since the latter are well established prognostic factors for non-small cell lung cancer, p53 aberrations may also be a predictor of tumor aggressiveness.

Aged↗
PubMed1993

Transesophageal measurement of left atrial refractoriness.

During electrophysiological evaluation of supraventricular arrhythmias the transesophageal (TEEP) approach may be the first step but is limited in information available. One difficulty is in measuring left atrial refractoriness, as left atrial capture is seldom detectable either on ECG or via an esophageal lead. The problem may be eliminated and left atrial refractoriness measured via the esophagus, utilizing two or three extrastimuli to scan diastole to determine whether the atrial refractory period has been entered by the first extrastimulus. Measurement of left atrial and/or atrioventricular node or accessory pathway refractoriness then becomes possible.

Adult↗
PubMed1993

Toxoplasma gondii virulence: changing pattern under different maintenance conditions.

Toxoplasma gondii parasites were isolated in vitro and in vivo from a hare that had died of disseminated toxoplasmosis. Intraperitoneal inoculation of either homogenate of hare organs or parasites isolated on culture produced chronic infection in mice. However, a progressive increase of virulence following subsequent mouse-to-mouse transfections was observed. These findings suggest that host-parasite interaction plays a major role in determining the degree of pathogenicity, and that in vitro and in vivo isolation, if not followed by subsequent passages, may fail to reveal major differences in virulence between isolates.

Animals↗
PubMed1993

Ras oncogene transformation of human B lymphoblasts is associated with lymphocyte activation and with a block of differentiation.

The p21ras small GTP binding proteins participate in signal transduction from cell surface receptors and affect neoplastic transformation and development in many different cell types. In the present study, we examined the relationship between ras transformation and differentiation of human B lymphocytes. We show that the constitutive expression of the T24 Ha-ras oncogene in EBV-immortalized B lymphoblasts was associated with the induction of the interleukin 2 receptor alpha subunit, with an impaired immunoglobulin gene expression, altered adhesion properties and increased survival in serum-free medium. Since induction of the IL-2 receptor alpha subunit is a hallmark of lymphocyte activation, we suggest that p21ras naturally triggers B cell activation. The ras-transformed lymphocytes displayed a fully functional IL-2r, as assessed by c-fos induction following treatment with IL-2; nevertheless, they were not growth stimulated by this lymphokine. The decreased expression of immunoglobulin genes indicates that the ras oncogene blocks terminal differentiation to plasma cells, possibly by inhibiting the activity of lymphocyte-specific transcription factors. Somewhat unexpectedly, the constitutive p21ras activity did not cause an increased DNA binding of transcription factors PEA1 (AP1), PEA3, Oct-2 or NF-kB.

B-Lymphocytes↗
PubMed1992

[Electrocardiogram ambulatory monitoring: technological evolution and current prospectives].

The value of ambulatory ECG monitoring in the investigation of arrhythmic or ischemic events with paroxysmal patterns is well-known and its use is widespread. More recently, technical advances in informatics and in ECG signal digitizing have rapidly developed the current available ambulatory ECG instruments, reducing the time necessary for pattern analysis meanwhile assuring acceptable accuracy and reliability of the results. ECG recording techniques other than traditional Holter monitoring are now available such as transtelephonic transmission of ECG signal recorded in real time or previously stored in solid state memory by intermittent recorders that can be switched on by the patients himself at the first prodroms or at the end of the event. These "loop recorders" make it possible to indefinitely extend ECG monitoring time, reducing costs and increasing record sensitivity in comparison to conventional Holter monitoring. Moreover, recent technological development of Holter monitoring makes it possible to perform heart rate variability analysis and late potentials research in addition to traditional analysis of cardiac rate and ventricular repolarization. Thus Holter recording may become, combined with other usual risk factors, a polyparametrical non invasive approach to sudden cardiac death risk assessment characterised by low cost/benefit ratio and by large screening capacity.

Arrhythmias, Cardiac↗
PubMed1991

Host genetic background effect on the frequency of mouse mammary tumor virus-induced rearrangements of the int-1 and int-2 loci in mouse mammary tumors.

The frequency with which int-1 and int-2 are rearranged in mouse mammary tumors by mouse mammary tumor virus (MMTV)-induced insertional mutagenesis is a consequence of the host genetic background. In 75% of C3H mammary tumors, int-1 is rearranged by MMTV insertion, whereas only 30% of BALB/cfC3H tumors contain a virus-induced rearrangement of int-1. This difference is significant (P less than 0.005) and could not be accounted for by the potentially additive effect of the genetically transmitted Mtv-1-encoded virus in C3H mice. Similarly, MMTV-induced rearrangement of the int-2 gene in mammary tumors of the R111 mouse strain (59%) occurred at a significantly (P less than 0.025) higher frequency than in BALB/cfR111 (25%) mammary tumors. Moreover, in BALB/cfR111 mammary tumors, there is evidence that rearrangement of int-1 and int-2 does not occur independently (P less than 0.025). These results suggest that the long history of inbreeding for high tumor incidence of C3H and R111 mouse strains has selected for the fixation of host mutations which either complement the action of the particular int gene or affect the sensitivity of specific subpopulations of mammary epithelium to infection by particular strains of MMTV.

Animals↗
PubMed1991

[Holter monitoring with a pill-shaped esophageal electrode].

This study analyzes the possibility of using an oesophageal lead in the ambulatory ECG monitoring in order to improve the diagnostic effectiveness of the method by reliable identification of atrial activity. The oesophageal Holter monitoring was performed on 19 patients (pts) (8 F and 11 M, aged 34 to 79 years). These patients posed precise diagnostic problems unsolved by previous conventional Holter recordings. The oesophageal Holter recording was carried out with a Spacelabs recorder, model 90205 with two channels. One electrode was positioned in the standard lead CM5 and the second in the oesophagus using an Esodyn 2 electrode with a dynamic configuration made by C.B-Bioelettronica (Calenzano, Florence). The oesophageal lead was connected with the recorder by filter model EHF-4. The electrode was swallowed by the patient and the best position regulated on the P diphasic deflection of the highest amplitude. The monitoring allowed correct identification of the P wave over a 24-hour period. The arrhythmia which required the oesophageal Holter monitoring was recorded again in 15 of 18 patients examined. In each of these cases it was possible to solve the diagnostic question. The following arrhythmias were found: constant time correlation between the P deflection and the QRS in accordance with a supraventricular tachycardia with intraventricular conduction delay (4 pts); A-V dissociation in accordance with a ventricular tachycardia (2 pts); pause caused by atrioventricular block 2:1 (1 pt), second degree sinus-atrial block (1 pt), blocked premature atrial beats (4 pts); premature ventricular and premature atrial beats with intraventricular conduction delay (3 pts).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[The physiopathology of dual-chamber cardiac stimulation. Apropos a case with a dual-chamber pacemaker, left atrial standstill and heart decompensation].

The paper describes the clinical case of an elderly patient with heart failure, the possessor of a dual-chamber pacemaker programmed in DDD mode, in whom a complete interatrial block with left atrial standstill was diagnosed. The authors discuss the physiopathological aspect of the case which is a paradigmatic example of the problems related to dual-chamber pacing. In particular, the utility of an echo-Doppler assessment of the mechanical activity of the atria is emphasized together with a careful choice of the optimal atrioventricular delay in programming and the follow-up of dual-chamber pacing.

Aged↗
PubMed1991

[Estimation using unipolar transesophageal recording of the interatrial conduction time in patients with paroxysmal atrial flutter and fibrillation].

Twenty-three consecutive subjects (age 46.7 +/- 21, range 13-78) addressed to our attention for symptoms attributed to documented or suspected supra ventricular arrhythmias underwent transesophageal electrophysiologic study. On the basis of the preliminary investigations 15 proved free from organic heart disease, 2 were affected with ischemic heart disease (secondary angina), 6 with hypertensive cardiomyopathy. In each patient the sensibility, specificity and positive predictive value of the following reports regarding the occurrence of paroxysmal fibrillation and flutter (Ffap) were evaluated: a) echo reports of left atrial enlargement; b) ECG signs of atrial enlargement; c) interatrial conduction time (TCIA) assessed with unipolar transesophageal recording. As TCIA we adopted the time interval intercurrent from the first low-voltage deflection of the esophageal P wave (far field) and the apex of the intrinsecoid deflection of the same wave. TCIA proved significantly longer in the 12 patients affected with Ffap compared with those free from documented paroxysmal or inducible arrhythmias or affected with paroxysmal junctional reciprocating tachycardias: 76.6 +/- 11 vs 51.8 +/- 11.7; p less than 0.001. A TCIA greater than 63 msec characterizes with satisfactory sensibility and specificity the occurrence of Ffap: sens. 75%, spec. 91%, positive predictive value 90%. Echo and ECG reports of atrial enlargement behave as highly specific but not sufficiently sensitive indexes of the occurrence of Ffap: sens. 42%, spec. 100%, pos. pred. val. 100% and sens. 17%, spec. 100%, pos.pred.val. 100% resp. We concluded that TCIA is an index correlated with and predictive of the occurrence of Ffap in patients symptomatic for cardiopalmus or neurologic symptoms in the absence of other arrhythmias detectable with Holter monitoring which are able to produce clinical symptoms.

Adolescent↗
PubMed1990

Protective effects of fructose-1,6-diphosphate on acute and chronic doxorubicin cardiotoxicity in rats.

The effects of fructose-1,6-diphosphate, an intermediate metabolite of glycolysis, on acute and chronic cardiotoxicity of doxorubicin were investigated in rats. In the acute study, urethane-anaesthetized Wistar female rats treated with 10 mg/kg i.v. doxorubicin developed a widening of the S alpha T segment, an impairment of +dP/dtmax, and tachycardia. Pretreatment with 375 and 750 mg/kg i.p. fructose-1,6-diphosphate prevented the S alpha T segment from widening, whereas only 750 mg/kg i.p. significantly attenuated the heart rate increase. Chronic cardiomyopathy was induced over a 6-week period by weekly doses of 3 mg/kg i.v. doxorubicin, being characterized in vivo by the progressive enlargement of the S alpha T segment and the occurrence of histological alterations and in vitro by a marked impairment of the inotropic response elicited by adrenaline in isolated hearts from treated rats. Concurrent treatment with 150 and 300 mg/kg i.p. fructose-1,6-diphosphate thrice a week for 6 weeks did not lessen the chronic heart damage, whereas 600 mg/kg given i.p. significantly reduced the widening of the S alpha T segment and the severity of histological damage in vivo, as well as significantly improving the contractile responses of hearts in vitro. These findings suggest that the administration of fructose-1,6-diphosphate plays a protective role in the acute and chronic cardiotoxicity of doxorubicin in the rat.

Acute Disease↗
PubMed1990

Cardiac toxicity and antitumor activity of 4'-deoxy-4'-iodo-doxorubicinol.

The acute and chronic cardiotoxicity as well as the cytotoxicity of 4'-deoxy-4'-iodo-doxorubicinol (I-DXRol), the major metabolite of the doxorubicin (DXR) derivative 4'-deoxy-4'-iodo-DXR (I-DXR), were compared with those of I-DXR and DXR. In the acute study, anesthetized rats received i.v. DXR (10 mg/kg), I-DXR (4 mg/kg), or I-DXRol (4 mg/kg) and were monitored for ECG (S alpha T segment and T wave), systolic (SBP) and diastolic (DBP) blood pressure, the first derivative of the systemic arterial pressure (SA dP/dtmax), and heart rate. Treatments induced a significant widening of the S alpha T segment, but I-DXRol was significantly less toxic than I-DXR or DXR. As compared with control values, DXR induced a marked increase in SBP and DBP and a decrease in SA dP/dtmax, whereas I-DXR and I-DXRol induced modest changes in hemodynamic parameters. In the chronic study, 3 mg/kg DXR given to rats by i.v. bolus once a week for 3 weeks resulted in severe chronic cardiotoxicity that lasted 6 weeks and was characterized by S alpha T-segment widening, T-wave flattening, and severe cardiac histological damage. Doses of 1.2 mg/kg I-DXR and 1.2 and 2.4 mg/kg I-DXRol, given i.v. once a week for 3 weeks, and 3.6 mg/kg I-DXRol given as a single dose were associated with a significant T-wave voltage reduction; I-DXR and 2.4 mg/kg I-DXRol induced significant histological alterations of cardiac tissue as compared with control values, whereas modest alterations of heart tissue were observed after injections of 1.2 and 3.6 mg/kg I-DXRol in three doses and in a single dose, respectively. The cytotoxicity of the three anthracyclines against one glioblastoma cell line and two human small-cell lung cancer lines was similar. Results indicate that the acute cardiotoxicity of I-DXRol is lower than that of I-DXR and DXR, whereas the chronic heart damage is similar to that induced by I-DXR and significantly lower compared than that caused by DXR. Moreover, the cytotoxicity of the metabolite appears to be similar to that of I-DXR and DXR. The lack of additional cardiac toxicity due to I-DXRol further supports the lower overall cardiac toxicity of I-DXR, which retains a cytotoxic activity similar to that of the parent drug.

Animals↗
PubMed1990

Phase II study of high-dose epirubicin in untreated patients with small-cell lung cancer.

Eighteen previously untreated patients with histologically confirmed small-cell lung cancer were treated with high-dose epirubicin (course 1, 100 mg/m2; courses 2-6, 140 mg/m2, day 1), every 3 weeks. Overall response rate was 33% (95% confidence limits, 14-52%), including two complete and four partial responses. The response rates for limited (n = 11) and extensive (n = 7) disease patients were 45% and 14%, respectively. With a median follow-up of 18 months, estimated 2-year survival of all patients was 29% and the median duration of response 18.5 months. The dose-limiting toxicity was myelosuppression, with a median granulocyte nadir of 1,150/mm3; 39% of patients had neutropenic fever. Nausea/vomiting, alopecia, and stomatitis were the most common nonhematological toxicities, usually mild to moderate. Acute cardiac toxicity was unusual and no episodes of congestive heart failure were observed. Cumulative doses of 800 mg/m2 were associated with moderate cardiotoxicity (grade 2), as assessed by endomyocardial biopsy and electron microscopy analysis. These results indicate that epirubicin, at the present doses and schedule, is an active single agent in patients with small-cell lung cancer, with acceptable general and moderate cardiac toxicity.

Aged↗