Search PubMed⌕ Search

Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 127 records · Page 7Linked to original sources
PubMed2001

Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis.

Desmoids represent the most important cause of death, after colorectal cancer, in patients affected with familial adenomatous polyposis (FAP), an inherited disease due to mutations in the APC gene. The aims of our study were to estimate the risk of developing desmoids in FAP patients and to evaluate the association between desmoids and different risk factors. The occurrence of desmoids, colorectal cancer and other extra-colonic manifestations were assessed in 897 FAP patients, 653 of whom were also investigated for APC mutations. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using an unconditional multiple logistic regression model. Desmoids developed in 107 patients (11.9%), with a cumulative risk of 20.6%. Females had a significantly higher risk than males (OR = 2.1; 95% CI 1.4-3.1). Family history of desmoids (OR = 8.75; 95% CI 5.66-13.51), osteomas (OR = 2.9; 95% CI 1.8-4.8) and epidermoid cysts (OR = 1.8; 95% CI 1.1-3.2) was also significantly associated with the occurrence of disease. Subjects with APC mutations beyond codon 1444 had a 12-fold increased risk, compared with patients with mutations located upstream. Mutations beyond codon 1309 conferred a 17-fold higher risk, compared with mutations upstream codon 452. Multivariate analysis identified as independent predictors mutation beyond codon 1444 (OR = 6.2; 95% CI 2.5-15.8), family history of desmoids (OR = 5.8; 95% CI 3.1-10.6), female gender (OR = 2.1; 95% CI 1.1-3.8) and the presence of osteomas (OR = 1.9; 95% CI 1.1-3.4). Our results indicate that integrating genetic and clinical data is helpful in defining subgroups of patients at higher risk for desmoids, who may benefit from specific prevention programs.

Adenomatous Polyposis Coli↗
PubMed2001

Analysis of mutational effects at the HPRT locus in human G(0) phase lymphocytes irradiated in vitro with gamma rays.

The mutational effects of ionising radiation at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus were studied in human peripheral blood G(0) phase lymphocytes irradiated in vitro with gamma rays. The presence of radiation induced mutants was assessed by selecting the HPRT mutants every week on the basis of 6-thioguanine resistance up to 1 month after irradiation. A dose-related increase of 14.25x10(-6) mutants/Gy was measured after an expression time of 7 days. After 2 weeks from culture starting the fraction of clonable cells in irradiated and control cell populations decreased, limiting the measurements of mutant frequency. The mutational spectrum of the HPRT gene was determined by PCR analyses in a total of 99 mutant clones derived from irradiated lymphocytes. The independent origin of mutant clones carrying the same mutation was assessed by analysing the TCR gamma gene rearrangements. The results showed a dose-related increase of deletion mutants up to 3Gy, whereas point mutation frequency increased only up to 2Gy. Two preferentially deleted regions were identified; one involving the HPRT exon 3, and another one the 3'-terminal and the 3'-flanking region of the gene. One complex mutation involving a non-contiguous deletion of exons 2-5 and 7/8 was observed among the mutants isolated after 3Gy irradiation.

Base Sequence↗
PubMed2001

Comparison of control of Listeria by nitric oxide redox chemistry from murine macrophages and NO donors: insights into listeriocidal activity of oxidative and nitrosative stress.

The physiological function of nitric oxide (NO) in the defense against pathogens is multifaceted. The exact chemistry by which NO combats intracellular pathogens such as Listeria monocytogenes is yet unresolved. We examined the effects of NO exposure, either delivered by NO donors or generated in situ within ANA-1 murine macrophages, on L. monocytogenes growth. Production of NO by the two NONOate compounds PAPA/NO (NH2(C3H6)(N[N(O)NO]C3H7) and DEA/NO (Na(C2H5)2N[N(O)NO]) resulted in L. monocytogenes cytostasis with minimal cytotoxicity. Reactive oxygen species generated from xanthine oxidase/hypoxanthine were neither bactericidal nor cytostatic and did not alter the action of NO. L. monocytogenes growth was also suppressed upon internalization into ANA-1 murine macrophages primed with interferon-gamma (INF-gamma) + tumor necrosis factor-alpha (TNF-alpha or INF-gamma + lipid polysaccharide (LPS). Growth suppression correlated with nitrite formation and nitrosation of 2,3-diaminonaphthalene elicited by stimulated murine macrophages. This nitrosative chemistry was not dependent upon nor mediated by interaction with reactive oxygen species (ROS), but resulted solely from NO and intermediates related to nitrosative stress. The role of nitrosation in controlling L. monocytogenes was further examined by monitoring the effects of exposure to NO on an important virulence factor, Listeriolysin O, which was inhibited under nitrosative conditions. These results suggest that nitrosative stress mediated by macrophages is an important component of the immunological arsenal in controlling L. monocytogenes infections.

2-Naphthylamine↗
PubMed2001

Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis.

Colorectal cancers with high-frequency microsatellite instability show peculiar clinicopathological features and a favorable clinical outcome. We investigated whether the improved prognosis for these cancers is related to the content of activated cytotoxic intraepithelial T lymphocytes. Microsatellite instability and the amount of activated cytotoxic lymphocytes were analyzed according to clinicopathological features, survival, and disease recurrence in 109 right-sided colon carcinomas from 245 consecutive patients with stage II/III colon cancer that underwent radical surgery. High-frequency microsatellite instability was found in 43% of stage II/III proximal colon cancers and was associated with significantly higher numbers of activated cytotoxic lymphocytes. High-frequency microsatellite instability, as well as the content of intratumoral-activated cytotoxic T lymphocytes correlated with improved overall and disease-free survival, particularly in patients with stage III tumors. Multivariate analysis revealed that patients with both features had a risk of death and relapse markedly lower than that associated with microsatellite status or intratumoral cytotoxic lymphocytes separately. The presence of local cytotoxic immune responses is probably the major determinant of the good clinical course of patients with microsatellite unstable colon cancer. Furthermore, high-frequency microsatellite instability coupled with a high content of intratumoral cytotoxic lymphocytes may identify a subset of colon cancer patients with a favorable clinical outcome, particularly in stage III disease.

Aged↗
PubMed2001

Weekly docetaxel as II line therapy in non-small cell lung cancer: an interim analysis of a phase II study.

To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line treatment in non-small cell lung cancer (NSCLC), in November 1999, we started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age <or=75 years; evaluable or measurable progressive lesions; PS (ECOG) 0-2; adequate haematology and biochemistry parameters; no serious concurrent diseases; no symptomatic brain lesions; and informed consent. The end points were assessment of overall response rate, toxicity and quality of life (QoL). Patients were re-evaluated at the end of every cycle. An interim analysis of 18 patients (16 M) was performed. Weekly courses were 132; 16 of 18 patients were evaluable for response and 17 of 18 for toxicity. Two of the 16 patients (12.5%) had a partial response (95% CI: 10.5-14.7%). Haematological toxicity was very mild: grade 1-2 neutropenia occurred in four patients, grade 3 neutropenia in two patients; grade 1-2 anaemia in four patients; and grade 1-2 thrombocytopenia in two patients. Non-haematological toxicity was also very mild, with the exclusion of asthenia (grade 1-2 in ten patients and grade 3 in five patients) and alopecia (grade 1-2 in seven patients and grade 3 in eight patients). No cases of grade 4 toxicity were observed. No QoL evaluations were reported in this interim analysis. In conclusion, these preliminary data confirm that weekly D results in tolerable toxicity in pre-treated NSCLC. Myelo-suppression, the dose-limiting toxicity of every 3 week schedules, is not a clinically relevant problem when D is administered weekly. G-CSF was used only sporadically in four patients, and no febrile neutropenia was reported. Patients were pre-treated with dexamethasone and no allergic reactions were seen. Although the therapeutic activity appears to be comparable to that of every 3 week schedules, more data are necessary before definite conclusions can be drawn. Accrual of patients is still ongoing.

Adult↗
PubMed2001

A new model of integrated home care for the elderly: impact on hospital use.

The objective of the present study was to examine the effect of a home care program based on comprehensive geriatric assessment-Minimum Data Set for Home Care-and case management on hospital use/cost of frail elderly individuals. We determined all hospital admissions and days spent in hospital during the first year since the implementation of the home care program, and compared them to the rate of hospitalization that the same patients had experienced in the year preceding the implementation of such program. Following the implementation of this program, there was a significant reduction of the number of hospitalizations (pre 44% vs. post 26%, P < 0.001), associated with a reduction of hospital days, both at the individual patient level and for each admission. In conclusion, an integrated home care program based on the implementation of a comprehensive geriatric assessment instrument guided by a case manager has a significant impact on hospitalization and is cost-effective.

Aged↗
PubMed2001

EsophaCoil for palliation of dysphagia in unresectable oesophageal carcinoma: short- and long-term results.

BACKGROUND AND AIM: Few reports have shown that EsophaCoil is an effective and safe prosthesis for palliation of malignant oesophageal dysphagia. A single centre experience using this type of prosthesis is reported. PATIENTS AND METHODS: Between January 1995 and September 2000, 42 consecutive patients, 41 with unresectable oesophageal cancer and one with oesophageal stenosis secondary to lung cancer, were treated with 44 EsophaCoils (2 patients received 2 stents). Tumours were located in lower third of oesophagus and/or gastric cardia in 22 cases, in middle third in 18 and in upper third in 2. Mean stricture length was 5.3 cm. Implantation was performed on hospitalized patients. RESULTS: EsophaCoil placement was successful all 44 times and was followed by complete expansion of the prostheses. There were no major procedure-related complications or deaths. Dysphagia score improved from mean of 2.9 to 1.3 within 24 hours of stent implantation. Median hospital stay was 2.7 days. Late complications occurred in 14 patients (34.2%): 3 migrations into stomach, 7 tissue overgrowth, 2 late perforations and 2 food impactions. Mean survival time was 4.2 months (range 1-10). CONCLUSIONS: In our experience, full expansion of EsophaCoil was achieved in all cases. This result, was associated with high incidence of retrosternal pain. Relief of dysphagia score was identical to that obtained with other types of Self-Expanding Metal Stent. Coil design prevented tumour ingrowth and allowed retrieval of three migrated stents. Mean survival time was similar to that reported in larger series using different types of Self-Expanding Metal Stent.

Adenocarcinoma↗
PubMed2001

Dietary patterns, nutrient intake and gastric cancer in a high-risk area of Italy.

OBJECTIVES: To better understand the role of overall dietary patterns and major energy-providing components in gastric cancer etiology. METHODS: In a population-based case-control study conducted in a high-risk area in central Italy, 382 gastric cancer cases and 561 controls were available for analysis. Multivariate models based on energy-adjusted residuals and completely partitioned logistic models were used; dietary patterns were evaluated by factor analysis and multiple correspondence analysis. RESULTS: Gastric cancer risk was inversely related to high energy-adjusted intakes of vegetable fat, sugar, beta-carotene, vitamin C, alpha-tocopherol, and nitrates. In contrast, significant positive associations emerged with high intake of protein, nitrite, and sodium. According to energy decomposition models, gastric cancer risk increased with increasing intake of protein and decreased with increasing intake of sugar and total fat. The pattern analysis identified four dietary profiles, overall explaining 75% of total dietary variability. Two patterns, named "traditional" and "vitamin-rich", were strongly associated with gastric cancer risk and overall accounted for 44% of estimated gastric cancer attributable risk. The other two patterns, "refined" and "fat-rich", were not consistently associated with gastric cancer. CONCLUSION: Innovative methodological approaches may contribute to better evaluation of the complex relationship between diet and cancer risk and to planning dietary interventions.

Adult↗
PubMed2001

Ethanol-induced oxidative stress in rat astrocytes: role of HSP70.

Ethanol intake is associated with increase in lipid peroxidation and formation of reactive oxygen species in different cerebral areas, in neurons as well as in astrocytes. The latter's integrity is essential for the normal growth of neurons. In previous studies we observed, in different cerebral areas of both acutely and chronically ethanol-treated rats, correlation between ethanol-induced oxidative stress and the increased expression of HSP70 (70 kDa heat shock proteins), chaperonins having a protective and stabilizing effect on stress-induced cell injury. In this study we examined, in vitro, the role of HSP70 on chronically ethanol-treated rat astrocytes by transfection with an anti-HSP70 antisense oligonucleotide. The results show that treatment with ethanol, from 50 to 100 mmol/L, induces a dose-dependent increase in the production of reactive oxygen species and of HSP70 levels, together with an impairment of the respiratory chain activity and a decrease in cell viability. In addition, our data indicate a drastic reduction of cellular metabolism in HSP70-deprived astrocytes, particularly when these cells were also ethanol-treated. In fact, transfection with HSP70 antisense induced moderate oxidative damage in control astrocytes and, consequently, a drastic decrease in the viability of ethanol-treated cells, with the mitochondrial functionality being particularly affected. Our results confirm that heat shock proteins confer a survival advantage to the astrocytes, preventing oxidative damage and nuclear DNA damage as well, and suggest the development of new drugs exerting a cytoprotective role either in physiological, or pathological conditions.

Animals↗
PubMed2001

Survival, root colonisation and biocontrol capacities of Pseudomonas fluorescens F113 LacZY in dry alginate microbeads.

Cells of Pseudomonas fluorescens F113 LacZY were encapsulated in alginate and their survival and ability to colonise sugar beet were evaluated. To assess survival, the formulation, composed of dry alginate microbeads of 300- to 700-microm diameter, was stored 1 year at 28+/-2 and 4+/-2 degrees C and then tested against pathogenic fungi Pythium ultimum and Rhizoctonia solani in in vitro inhibition experiments. The same material was also used as inoculant for protection of sugar beet against Py. ultimum in microcosm experiments. The results obtained indicated that, although drying alginate beads resulted in a significant reduction of bacterial viability, the use of microbeads enabled a satisfactory level of root colonisation and protection, at least under microcosm conditions. The capability of the encapsulated cells to produce the antifungal metabolite 2,4-diacetylphloroglucinol (Phl) was not significantly affected by 12 months storage.

Alginates↗
PubMed2001

Placing the newborn on the maternal abdomen increases the volume of umbilical cord blood collected.

Haematopoietic stem cell transplantation is an important therapy for certain haematological and malignant disorders. Umbilical cord blood contains a high proportion of potentially transplantable haematopoietic progenitor cells. However, the use of cord blood stem cell transplantation is limited by the low number of stem cells obtainable from a single cord blood donor. The aim of our study was to investigate the possibility that procedures during delivery might influence the number of umbilical cord blood haematopoietic progenitor cells available for transplantation. We assessed the effects of upper and lower positions of the newborn infant on the yield of cord blood stem cells in 51 vaginal deliveries. Neonates in the upper position group were placed by the midwife on the maternal abdomen immediately after birth, while those in the lower position group were placed on the delivery table, below the maternal introitus. The total volume of cord blood and the total number of CD34+ cells collected from babies in the upper position group were significantly higher than those from babies in the lower position group. There were no significant differences in cord blood haemoglobin levels and white blood cell counts between the two groups, nor were there any adverse effects in the newborn infants. The simple manoeuvre of placing the newborn on the maternal abdomen after delivery may thus increase the yield of transplantable haematopoietic progenitor cells in cord blood.

Abdomen↗
PubMed2001

Early clamping of umbilical cord blood and foetal CD34 enrichment.

We describe the relation between clamping time and blood volume collected, and two enrichment systems of CD34+ stem cells from umbilical cord blood, in order to determine the criteria for an excellent recovery with high proliferative ability and bone marrow reconstitution. After an obstetrician-based cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies, negative selections, using the Stem Sep method, or with a positive cells selection owing to their surface CD34 antigens, using the Mini Macs system. An excellent recovery of haematopoietic progenitors--burst forming unit erythroid; colony-forming unit granulocyte and macrophage; and colony-forming unit granulocyte, erythroid, monocyte, and macrophage--inversely related to an increase in clamping time, was achieved using the Mini Macs system (54% of colonies with a 90% purity), while the recovery of haematopoietic progenitors was 35% (with a 80% purity) using the Stem Sep method. By clamping umbilical cord blood at an early stage, we obtained a greater number of CD34+ cells, and their clonogenic activity increased with enrichment. This is particularly useful considering that the number of CD34+ stem cells contained in a unit of placental blood is sufficient for transplanting into a child but not for an adult engraftment. Thus, using these methods, we obtain a larger number of CD34+ stem cells. This increases the possibility of reducing graft versus host disease in adult patients and produces survival rates similar to the ones we observed in transplantation of bone marrow from unrelated donors.

Antigens, CD↗
PubMed2001

Antiarrhythmic drug use in the implantable defibrillator arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study.

BACKGROUND: Previous retrospective or observational series suggest that many patients with an implantable cardioverter-defibrillator (ICD) will be treated with antiarrhythmic drugs (AADs) to modify the frequency or manifestation of recurrent ventricular arrhythmias. The relative clinical benefit, however, is uncertain, and deleterious interactions can occur. The objective of this clinical investigation was to study the need for, and effects of, concomitant AAD use with the ICD in a prospectively defined cohort. METHODS: All patients randomly assigned to the ICD arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) study were followed for the addition of class I or III AADs ("crossover") after hospital discharge. Addition of AADs was strictly regulated by AVID protocol. The timing and reasons for crossover and the effects on ventricular arrhythmia recurrence were analyzed. Patients were excluded if they required AADs before hospital discharge after index arrhythmias or if they had no ventricular arrhythmia before initiation of AADs. RESULTS: After a median follow-up of 135 days, 81 (18%) of the 461 eligible patients required AADs and formed the crossover group. The primary reason for crossover was frequent ICD shocks in 64% of patients. The most common AAD selected was amiodarone (in 42%). Independent predictors of crossover were lower ejection fraction, absence of ventricular fibrillation, or presence of nonsyncopal ventricular tachycardia at presentation, prior unexplained syncope, female sex, and history of cigarette smoking. Before AAD use, the 1-year arrhythmia event rate was 90%; after AAD, the event rate was only 64% (P =.0001). The time to first event was extended from 3.9 +/- 0.7 months to 11.2 +/- 1.8 months. There were 1.4 +/- 3.7 fewer ICD therapy events (P =.005) after crossover, predominantly accounted for by reduction in shocks rather than antitachycardia pacing therapies. CONCLUSIONS: The majority of patients who receive ICDs for sustained ventricular tachycardia or ventricular fibrillation can be treated without AADs. Most commonly, AADs are added to combat frequent ICD shocks, which are successfully reduced by AAD therapy.

Aged↗
PubMed2001

Indian medicinal plants as antiradicals and DNA cleavage protectors.

Celastrus paniculatus L. (Celastraceae) (CP), Picrorhiza kurroa L. (Scrophulariaceae) (PK) and Withania somnifera L. (Solanaceae) (WS) are Indian medicinal plants having a remarkable reputation, as a factor of health care, among the indigenous medical practitioners. The plants exhibit varying degrees of therapeutic value some of which useful in the treatment of cognitive dysfunction, epilepsy, insomnia, rheumatism, gout, dyspepsia. In this work, we have investigated the free radical scavenging capacity of methanolic extracts from CP, PK, WS and the effect on DNA cleavage induced by H2O2 UV-photholysis. In addition, we investigated whether these plant extracts are capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized fibroblasts. These extracts showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage; methanolic extracts from PK was more active than extracts from CP and WS. These results were confirmed by a significant protective effect on H2O2-induced cytoxicity and DNA damage in human non-immortalized fibroblasts. These antioxidant effects of active principle of CP, PK and WS may explain, at least in part, the reported anti-stress, immunomodulatory, cognition-facilitating, anti-inflammatory and antiaging effects produced by them in experimental animal and in clinical situations and may justify the further investigation of their other beneficial biological properties.

Antioxidants↗