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Biomedical subjects

M Gentile

Publications and source records attributed to M Gentile.

At least 73 records · Page 4Linked to original sources
PubMed2001

Surgical treatment of lung cancer invading chest wall: a retrospective analysis of 110 patients.

OBJECTIVE: To retrospectively assess the results of surgical treatment in a consecutive series of 110 patients with Stage IIb and IIIa non small cell lung cancer (NSCLC) invading chest wall. METHODS: A series of 110 patients underwent surgery for Stage IIb and IIIa NSCLC with involvement of chest wall. There were 101 male and 9 female patients, mean age was 61.4 (range 32--74), 52 (47.3%) of them complaining for chest pain. Surgical procedures were pneumonectomy in seven patients (6.4%), lobectomy in 73 (66.4%), bi-lobectomy in six (5.4%) and wedge resection in 24 (21.8%). In 63 patients (57.3%) an extrapleural resection was performed while in the other 47 (42.7%) an 'en bloc' resection of tumor with chest wall was required. In 22 patients (76.3%) repair was achieved by muscle flap while in 8 (26.7%) a prosthesis was required. Five-year survival was computed using the Kaplan--Meier method; P values correspond to the log-rank test. RESULTS: There were neither intraoperative nor postoperative deaths. Postoperative staging revealed 83 T3N0M0, 17 T3N1M0 and 10 T3N2M0. Mean postoperative hospital stay was 17.7 days (range 5--40). For N0 patients 5 year survival was 47% (39/83) and no significant difference was noted when extrapleural and 'en bloc' resection groups were compared (P = 0.08). In N1/N2 patients no survival was observed (0/27) and comparison between surgical procedures was not statistically significant (P = 0.41). Moreover when N0 patients were compared with N1 patients the difference in survival was significant for both extrapleural (P = 0.02) and 'en bloc' (P = 0.04) groups. No difference was noted when the two surgical procedures were compared independently form N status (P = 0.94). Within the group of patients undergone 'en bloc' resection survival was significantly better for N0 patients as in the group of extrapleural resection. CONCLUSION: Surgical treatment of Stage IIb and IIIa NSCLC invading chest wall by extrapleural or 'en bloc' resection is widely adopted and justified by the good results in terms of morbidity and relief of pain. Survival is always depending on the N status.

Adult↗
PubMed2001

Protein accumulation and gene mutation of p53 in bilateral breast cancer. South-East Sweden Breast Cancer Group.

The aim of this study was to investigate the frequency of p53 alterations in bilateral breast cancer and to evaluate a possible clonal relationship between the paired tumours regarding p53 alteration and other pathobiological variables. Tumours from 34 patients were investigated with immunohistochemistry, single strand conformation polymorphism analysis and DNA-sequence analysis applied to exons 5-8. Fifteen percent of the 68 tumours showed positive immunoreaction and/or presence of mutation. The occurrence of p53 accumulation was 9% and the prevalence of gene mutation 10%. No significant concordance was found between the tumours in the same patient for p53 alterations, progesterone receptor status or DNA ploidy. S-phase fraction showed a weak correlation, not statistically significant. Oestrogen receptor status was the only variable that exhibited a significant concordance. No convincing evidence was found for other associations between the paired tumours or for a high prevalence of p53 alterations in bilateral breast cancer.

Breast Neoplasms↗
PubMed2001

Management of patients with LUTS suggestive of BPH.

The QUIBUS study offers some insights into the current diagnosis and treatment of LUTS suggestive of BPH in Italy. As diagnosis is concerned, uroflowmetry and PSA testing were performed in a high percentage of cases (64 and 89%, respectively). Both transrectal ultrasonography and prostate biopsy were more frequent for increasing values of PSA, this suggesting that are used as screening procedures for prostate cancer. However, transrectal ultrasonography was performed overall in a large proportion of patients (61%), representing a routine examination in some centers. As treatment is concerned, the majority of QUIBUS patients had undergone or were undergoing medical therapy. Alphalytics were the drugs most commonly prescribed by urologists while primary care physicians showed the attitude to prescribe more frequently finasteride. On the surgical side, transurethral prostatectomy and open surgery were the most commonly employed procedures, suggesting that little room is left at present to minimally invasive procedures in Italy.

Adult↗
PubMed2001

Acute myocardial infarction caused by amphetamines: a case report and review of the literature.

Cardiotoxicity manifesting as myocardial ischemia is not generally recognized as a side effect of amphetamine use or abuse. However, at least 9 cases have been reported since 1987. In this report a case of acute myocardial infarction due to oral amphetamine therapy is presented. The patient was treated with thrombolytic therapy but there were no signs of reperfusion. His coronary cine-angiograms were normal. The literature regarding amphetamine use or abuse is also reviewed, and the possible mechanisms of this pathology are analyzed.

Adult↗
PubMed2000

Endothelial activation in patients with cardiac syndrome X.

BACKGROUND: The presence of endothelial dysfunction with increased endothelin-1 plasma concentrations in patients with cardiac syndrome X is still under debate. The aim of the present study was to evaluate the presence of endothelial dysfunction in patients with cardiac syndrome X. METHODS AND RESULTS: ++Endothelin-1 levels were evaluated with a sensitive radioimmunoassay with previous purification through reverse phase HPLC in 24 patients (3 men and 21 women, mean age 54+/-7 years) with typical angina, instrumental evidence of ischemia, and normal coronary angiograms both under baseline conditions and after oral glucose load (75 g D-glucose). We also measured plasma nitrite-plus-nitrate levels, a sharp index of endothelial nitric oxide production, and circulating concentrations of the soluble fraction of the endothelial adhesion molecule vascular cell adhesion molecule-1, a well-recognized marker of early endothelial dysfunction. Fourteen healthy subjects (1 man and 13 women, mean age 47+/-15 years) served as controls. There were no significant differences in baseline plasma endothelin-1 concentrations between patients and control subjects (0.55+/-0.34 versus 0.48+/-0.22 pg/mL, P=0.503). Plasma nitrite-plus-nitrate and soluble vascular cell adhesion molecule-1 concentrations were also similar between the 2 groups. After glucose ingestion, circulating endothelin-1 concentrations were significantly higher in patients with cardiac syndrome X than in control subjects (P<0.03 at 60, 90, and 120 minutes). CONCLUSIONS: Our findings show that no basal endothelial damage is present in patients with cardiac syndrome X. Nevertheless, increased responsiveness of endothelin-1 to glucose loading suggests that patients with cardiac syndrome X present an increased susceptibility to releasing endothelin-1 under stressful circumstances.

Chromatography, High Pressure Liquid↗
PubMed2000

Increasing proportion of late diagnosis of HIV infection among patients with AIDS in Italy following introduction of combination antiretroviral therapy.

We analyzed trends over time and determinants of late diagnosis of HIV infection among people diagnosed with AIDS in 1986 to 1998 in a tertiary care center in Rome, Italy. Information on the date of a first HIV test was collected prospectively, in addition to data routinely collected for AIDS reporting. Patients with AIDS were defined as "late testers" if the time interval between first positive HIV test result and AIDS diagnosis was < or = 3 months. Overall, 503 people with AIDS of 1977 included in the analysis (25.4%) were late testers. the proportion of late testers decreased from 62.5% in 1986 to 16% in 1995. Thereafter, this proportion increased to 20.5% in 1996, 33.7% in 1997, and 36.6% in 1998. In multivariate analysis, the following variables were significantly associated with late testing: AIDS diagnosis in years 1986 to 1993 or 1997 to 1998 compared with 1995, male gender, age > or = 45 years, men who have sex with men, heterosexual contacts, or having unknown transmission mode compared with intravenous drug users, and being born outside Italy. Since 1996, the overall number of AIDS cases diagnosed at our center began to decrease whereas the number of late-testing AIDS patients did not decrease, resulting in an increasing proportion of late testers during the last 3 years of the study. This findings may reflect the effect of combination antiretroviral therapy in slowing progression to AIDS of HIV-infected persons aware of their status. A relevant number of people still discover their HIV infection late and may therefore miss treatment opportunities. New testing strategies are needed to reach more people who engage in high-risk behaviors, especially those at risk for sexual transmission, and those born outside Italy.

Acquired Immunodeficiency Syndrome↗
PubMed2000

The effect of potent antiretroviral therapy and JC virus load in cerebrospinal fluid on clinical outcome of patients with AIDS-associated progressive multifocal leukoencephalopathy.

A multicenter analysis of 57 consecutive human immunodeficiency virus-positive patients with progressive multifocal leukoencephalopathy (PML) was performed, to identify correlates of longer survival. JC virus (JCV) DNA was quantified in the cerebrospinal fluid (CSF) by polymerase chain reaction. Two months after therapy, 4% of the patients without highly active antiretroviral therapy (HAART) and 26% with HAART showed neurologic improvement or stability (P=.03), and 8% and 57%, respectively, reached undetectable JCV DNA levels in the CSF (P=.04). One-year probability of survival was.04 without HAART and.46 with HAART. HAART and lack of neurologic progression 2 months after diagnosis were independently associated with longer survival. Among HAART-treated patients, a baseline JCV DNA <4.7 log, and reaching undetectable levels after therapy predicted longer survival. Survival of AIDS-related PML is improved by HAART when JCV replication is controlled.

AIDS Dementia Complex↗
PubMed2000

Secretory phospholipases A2 induce beta-glucuronidase release and IL-6 production from human lung macrophages.

Secretory phospholipases A2 (sPLA2s) are a group of extracellular enzymes that release fatty acids at the sn-2 position of phospholipids. Group IIA sPLA2 has been detected in inflammatory fluids, and its plasma level is increased in inflammatory diseases. To investigate a potential mechanism of sPLA2-induced inflammation we studied the effect of group IA (from cobra venom) and group IIA (human synovial) sPLA2s on human macrophages. Both sPLA2s induced a concentration- and Ca2+-dependent, noncytotoxic release of beta-glucuronidase (16.2 +/- 2.4% and 13.1 +/- 1.5% of the total content with groups IA and IIA, respectively). Both sPLA2s also increased the rate of secretion of IL-6 and enhanced the expression of IL-6 mRNA. Preincubation of macrophages with inhibitors of the hydrolytic activity of sPLA2 or cytosolic PLA2 did not influence the release of beta-glucuronidase. Incubation of macrophages with p-aminophenyl-mannopyranoside-BSA (mp-BSA), a ligand of the mannose receptor, also resulted in beta-glucuronidase release. However, while preincubation of macrophages with mp-BSA had no effect on beta-glucuronidase release induced by group IIA sPLA2, it enhanced that induced by group IA sPLA2. A blocking Ab anti-mannose receptor inhibited both mp-BSA- and group IIA-induced beta-glucuronidase release. Taken together, these data indicate that group IA and IIA sPLA2s activate macrophages with a mechanism independent from their enzymatic activities and probably related to the activation of the mannose receptor or sPLA2-specific receptors. The secretion of enzymes and cytokines induced by sPLA2s from human macrophages may play an important role in inflammation and tissue damage associated with the release of sPLA2s.

Aniline Compounds↗
PubMed2000

Histopathology of the digestive gland of an Antarctic limpet exposed to cadmium.

Histopathological alterations induced experimentally with cadmium (Cd) in Antarctic limpets (Nacella concinna), exposed for different times and concentrations were compared to controls. At the light microscope level, samples exposed to the contaminant for short periods (6, 12 and 24 h) at two different concentrations (0.25 and 0.5 mg l(-1)) showed no alterations compared to controls. After 48 h of exposure at a 0.5 mg l(-1) Cd concentration, vacuolisation of the basophilic cells was observed. After 72 h exposure, there was a marked loss of all the digestive gland structure, with cell autolysis and loss of basophilia.

Animals↗
PubMed2000

Involvement of PTEN mutations in the genetic pathways of colorectal cancerogenesis.

So far, somatic mutations of the PTEN gene have been found in several different neoplasms but not in colorectal tumours. As exons 7 and 8 of the PTEN coding sequence contain an (A)(6)repeat and mononucleotide repeat sequences are targets for mutations in tumours with microsatellite instability (MI), we screened a panel of sporadic colorectal tumours exhibiting MI to test whether PTEN gene repeats are frequently mutated in MI(+)colorectal cancers. Of 32 cases studied, seven mutations were found in six (18.75%) patients, as a PTEN biallelic frameshift mutation was observed in one case, with consequent loss of function of the gene. Loss of heterozygosity, evaluated in the remaining five cases using the microsatellite marker D10S541, was detected in two of three informative samples. To further address the role of the PTEN gene in MI(+)colorectal cancer, in the six patients with mutated PTEN, we analysed the mononucleotide repeats of six other genes: BAX, hMSH3, hMSH6, TGFbRII, IGFIIR and APC. In two of these six patients, mutations of the TGFbRII gene only were present, indicating that PTEN may have a role in the mutator pathway of colorectal tumorigenesis. Overall, these results indicate that PTEN mutations are selected for during tumorigenesis in MI(+)colorectal tumours. The mutation of both PTEN alleles and evidence that the PTEN protein is expressed in normal colon suggest that loss of function of this gene could play a direct role in tumorigenesis.

Colorectal Neoplasms↗
PubMed2000

Can seizures be the only manifestation of transient ischemic attacks? A report of four cases.

Several studies have investigated the frequency of epileptic seizures following ischemic strokes and transient ischemic attacks (TIAs). Little attention has been paid to the possibility that seizures may be precipitated by TIAs. We examined if seizures can be the only symptom of a TIA and how often this might occur. We performed a retrospective analysis of clinical charts and electroencephalograms of 160 consecutive patients evaluated for a first-ever seizure from January 1997 to December 1999 at Belluno General Hospital. From January to May 2000, 19 more first-ever seizure patients were evaluated directly. Four patients (2%) had seizures in the presence of important risk factors for ischemic stroke (atrial fibrillation in two patients, atrial fibrillation and ventricular mural thrombus in one patient, hemodynamically significant left carotid stenosis in one patient). Seizures were not accompanied by other neurological deficits or brain lesions on CT or MRI. As risk factors for brain ischemia are frequent in the general population not developing seizures, our results do not prove that the occurrence of seizures was more than casual in these patients. Yet they indicate that in a small percentage of patients, seizures can occur in a context highly suggestive of TIA, with no other focal deficits.

Aged↗
PubMed2000

Repetitive sequences upstream of the pfg27/25 gene determine polymorphism in laboratory and natural lines of Plasmodium falciparum.

The structure of the genomic region located upstream of the gametocyte-specific gene pfg27/25 of Plasmodium falciparum was analysed in laboratory lines and field isolates of the parasite. The gene is located in a subtelomeric region of chromosome 13 in parasite clones 3D7 and HB3. Analysis of laboratory lines and field isolates of P. falciparum indicated that polymorphism upstream of pfg27/25 is mainly due to the structure of a repetitive DNA region located at about half a kilobase from the pfg27/25 coding sequence. Different types of repetitive sequences are present in this region, whose copy number is variable in different parasite lines. In addition a GC-rich sequence element contained in this region, which is proposed to be the startpoint of pfg27/25 mRNA, presents either a direct or a reverse orientation in different parasite lines. Genomic deletions upstream of the pfg27/25 gene are also described in two laboratory lines of the parasite, which eliminate two newly identified malaria genes. orf P and orf Gap, from the genome of these parasites. One of them, orf Gap, deleted from the reference parasite clone 3D7, is abundantly expressed as mature mRNA in asexual parasites. PCR analysis on 64 field isolates of P. falciparum indicated that orf P and orf Gap sequences are present in all tested samples of naturally propagating parasites.

Animals↗
PubMed2000

Phase I-II study of gemcitabine and paclitaxel in pretreated patients with stage IIIB-IV non-small cell lung cancer.

Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I-II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m2 on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m2 on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m2; the paclitaxel dose level just below (210 mg/m2) was selected for phase Il evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23-57%). Median duration of response was 35 weeks (range, 8-102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8-108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely warranted.

Adult↗
PubMed1999

Inhibition of platelet-activating factor synthesis in human neutrophils and platelets by propionyl-L-carnitine.

Propionyl-L-carnitine (PrC) has been shown to exert beneficial effects in the treatment of myocardial and peripheral ischemia in man. These conditions are associated with the activation of circulating neutrophils and platelets. To determine whether PrC could affect the synthesis of lipid mediators known to influence neutrophil and platelet functions, we explored the effects of PrC on the synthesis of platelet-activating factor (PAF) and arachidonic acid (AA) metabolites. Preincubation (90 min) of human neutrophils with PrC (0.1-100 microM) inhibited the synthesis of PAF and of a PAF analog (1-alkyl-1'enyl-2-acetyl-sn-glycero-3-phosphoethanolamine: AEGPE) induced in vitro by the calcium ionophore A23187. In contrast, concentrations of PrC up to 100 microM did not influence the uptake of exogenous AA or the A23187-induced release of AA and eicosanoids from neutrophils in vitro. PrC (1 microM) also inhibited PAF synthesis from human platelets stimulated in vitro with thrombin, but had no effect on thrombin-induced aggregation. Oral administration of PrC (2 g/day for two weeks) to five normal volunteers resulted in a significant inhibition of PAF and AEGPE synthesis by neutrophils stimulated with A23187 ex vivo, with no effect on AA or eicosanoid release. These data indicate that PrC selectively inhibits in vitro and ex vivo PAF synthesis from human neutrophils and platelets without influencing AA metabolism or eicosanoid release. This effect of PrC might represent an additional mechanism by which this molecule can exert protective effects in tissue ischemia and in other inflammatory diseases associated with neutrophil and platelet activation.

Adult↗
PubMed1999

The benign cystic lymphoepithelial lesion of the parotid gland is a viral reservoir in HIV type 1-infected patients.

The presence of HIV-1 in cystic fluid aspirates from six cases of benign cystic lymphoepithelial lesion (BLL) of the parotid gland, a rare disorder affecting HIV-1-infected patients, has been investigated. HIV-1 p24 protein was present at a concentration ranging from 3 to 15 ng/ml, while it was undetectable in the peripheral blood of the same patients. The number of RNA copies of HIV-1 in the cystic fluids was high, ranging from 0.5 x 10(7) to 7.2 x 10(7) RNA copies/ml. BLL cystic fluid aspirates, despite the high level of HIV-1 RNA, were found to contain only a few infectious virions. The low infectivity correlated with the infrequent detection by electron microscopy of complete HIV-1 particles. The pathogenic mechanism leading to virus accumulation in the cystic fluid was studied by immunohistochemistry of tissue sections. p24 protein was associated with DRC-1+/S-100+ follicular dendritic reticulum cells, which were also present within the cystic cavities. Our findings are consistent with the possibility that the large amounts of virus present in the fluid derive from continuous shedding of HIV-1-infected cells from the surrounding lymphoid tissue.

Adult↗
PubMed1999

Association between CYP17 gene polymorphism and risk of breast cancer in young women.

Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T-->C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1-3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1. 9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41-1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women. Int. J. Cancer (Pred. Oncol.) 84:350-353, 1999.

Adult↗