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Biomedical subjects

A Rossi

Publications and source records attributed to A Rossi.

At least 109 records · Page 6Linked to original sources
PubMed2002

Selective cyclooxygenase-2 inhibitors and non-small cell lung cancer.

Lung cancer is the leading cause of death from cancer in most developed nations. The most common type of lung cancer is of non-small cell histology, representing approximately 80% of the total. Despite aggressive treatments in early stages and improvement of polychemotherapy outcomes in advanced disease, the five years survival rate for lung cancer remains under 15%. Fortunately, our improved knowledge of tumor biology and mechanisms of oncogenesis suggests several new potential targets for clinical research in cancer therapy. A substantial body of evidence indicates that cyclooxigenase (COX)-2 and prostaglandins (PGs) play an important role in tumorigenesis. Mechanisms involved in COX-2 participation in tumorigenesis and tumor growth include xenobiotic metabolism, angiogenesis stimulation, inhibition of immune surveillance and inhibition of apoptosis. COX-2 is frequently overexpressed in bronchial premalignancy, lung adenocarcinoma and squamous cell carcinoma and COX-2 overexpression is a marker of poor prognosis in surgically resected stage I non-small cell lung cancer. Treatment with COX-2 inhibitors reduces the growth of NSCLC cells in vitro and in xenograft studies. Recent studies have defined some of the mechanisms involved in COX-2 participation in NSCLC development and diffusion. These evidences support the hypothesis that selective COX-2 inhibitors (coxibs) may prove beneficial in the prevention and treatment of NSCLC.

Animals↗
PubMed2002

Chemotherapy of non-small cell lung cancer in elderly patients.

Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed over the age of 65 and approximately one-third of all patients with non-small cell lung cancer (NSCLC) are over the age of 70. Elderly patients tolerate chemotherapy poorly as compared to their younger counterparts, because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy, the standard medical treatment of advanced NSCLC. At present, for early stages of the disease there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemo-radiotherapy in locally advanced disease increases toxicity and seems to determine no survival advantage as compared to the radiation therapy alone. In advanced disease, single agent vinorelbine has proven to be active and well-tolerated, and compared to best supportive care, improves survival and perhaps even the quality of life. Gemcitabine is active and well tolerated as well. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared to single agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single agent chemotherapy should remain the standard treatment. The two main research-lines to be explored in the near future are the introduction of biological agents in the treatment schemes and the development of specifically designed schedules of cisplatin-based regimens. However, practicing a multidimensional geriatric awsessment for individualized treatment choice in NSCLC elderly patients is mandatory.

Age Factors↗
PubMed2002

[Alteration of spermatogenesis and Y chromosome microdelations. Analysis of the DAZ gene family].

The Y chromosome has a fundamental role in sex determination and regulation of spermatogenesis. Three regions (designated as AZFa, b, and c) on the long arm of this chromosome exist, deletions of which result in severe damage to spermatogenesis with azoospermia or severe oligozoospermia. Recent progresses in molecular biology and extraordinary development of assisted reproduction techniques contributed to the research on this chromosome and the genes involved in spermatogenesis. About 10-15% of subjects affected by azoospermia or severe oligozoospermia carry a deletion in one or more AZF regions, 60% of which involves AZFc. The genes responsible for the testicular phenotype observed in these subjects are DBY and USP9Y for AZFa, RBMY1 for AZFb, and DAZ for AZFc. In this article, the current knowledge on biology and genetics of the Y chromosome are reported with particular interest to deletions found in infertile subjects. Furthermore, the more recent advances on DAZ gene and its role in spermatogenesis and male infertility are discussed.

Animals↗
PubMed2002

EDU-CARE, a randomised, multicentre, parallel group study on education and quality of life in COPD.

Chronic obstructive pulmonary disease (COPD) represents one of the main causes of morbidity and mortality in the western world. Unfortunately, its therapy is largely palliative, the key aims of treatment being to reduce exacerbations, minimise symptoms, and improve patients' ability to perform their usual daily activities. In the absence of true disease-modifying treatments, the concept of rehabilitation has become important. In addition, it has been shown that educational and self-management programmes may play a role in the general treatment of COPD patients. This study was promoted by the Italian Association of Hospital Pulmonologists (AIPO) with the aim to verify changes and improvements induced by an educational programme validated by AIPO in patients with COPD. Edu-Care is a 6-month, multicentre, randomised, controlled, parallel-group study. In addition to treatment within the usual therapeutic schemes for COPD, patients were randomised to either the 'Educational' group, i.e. to receive a formal and structured educational programme, or the 'Normal General Advice' group, i.e. to receive the usual general advice given by general practitioners on life-style and on the disease's risk factors and treatment. A number of evaluations were performed: pulmonary function test, walking distance, quality of life, locus of control, register of number of exacerbations and hospital admissions. To date, of the 1,230 patients enrolled interim data are available from 1,003 patients. Males represent 85% of the study population. Smoking habit is quite a common status (21%). In the year prior to enrolment 34% of patients had one exacerbation, 49% 2-3 exacerbations, and 17% more than 3 exacerbations. Seventy-two percent of patients were not hospitalised over the year prior to enroLlment, while 22% were hospitalised once and 6% had more than 2 hospitalisations. Edu-Care is the first large study aimed to evaluate the efficacy of an educational programme for patients with COPD. AIPO wishes to make a contribution to this important field. This is the reason why Edu-Care includes a very large number of patients in numerous Italian centres throughout northern and southern Italy.

Activities of Daily Living↗
PubMed2002

[Pharyngeal and laryngeal hamartoma: case report].

In this report a case of laryngeal hamartoma is presented. Macroscopically this lesion is quite similar to a tumor but is actually a malformation derived from an error in the development of a healthy organ. Histologically, the hamartoma is composed of a proportionally abnormal mixture of tissues as compared to what is normally present in its anatomic site. The lesion is extremely rare and usually appears in the head and neck district, spleen, pancreas, lung and liver. The diagnosis is essentially based on histological examination. The treatment of choice consists of surgery and periodic follow-up. Differential diagnosis must consider other rare neoplasms such as rhabdomyoma and teratoma.

Female↗
PubMed2001

IR detection of NO2 using p+ porous silicon as a high sensitivity sensor.

Mesoporous silicon doped with 3.0 x 10(19) B atoms cm-3 (p(+)-type) is an insulating material which dramatically increases its electrical conductivity when exposed to traces of gaseous NO2; nitrogen dioxide chemisorption at the surface generates carriers, the population of which is readily evaluated through the intensity of IR absorption.

Journal Article↗
PubMed2001

Mechanisms of pulmonary gas exchange improvement during a protective ventilatory strategy in acute respiratory distress syndrome.

To investigate the mechanisms underlying improvement of arterial oxygenation during a protective ventilatory strategy (PVS) in early acute respiratory distress syndrome (ARDS), we studied eight patients during volume-controlled mechanical ventilation, keeping respiratory rate and fraction of inspired oxygen (FI(O(2))) (0.82 +/- 0.20) unchanged: (1) at baseline (tidal volume [VT] 10 to 12 ml x kg(-1); positive end-expiratory pressure [PEEP] 8 to 10 cm H(2)O); (2) during PVS (PEEP 2 cm H(2)O above the low inflexion point (P(FLEX)) and VT of 5 to 7 ml x kg(-1)); and (3) post-PVS, back to baseline conditions. Inert gas measurements were done after 30 min in each ventilatory modality. During PVS, Pa(O(2)) increased significantly from 93 +/- 27 to 166 +/- 77 mm Hg (p < 0.008) and Pa(CO(2)) rose from 39 +/- 7 to 57 +/- 11 mm Hg (p < 0.0002) because of the decrease in minute ventilation (V E) (-3.6 L x min(-1)) (p < 0.005). Both heart rate (HR, +13 min(-1)) (p < 0.002) and cardiac output (Q, +1.2 L x min(-1)) (p < 0.05) increased. Static respiratory system linear compliance increased from 36 +/- 14 to 44 +/- 16 ml. cm H(2)O(-1) (p < 0.0002). PVS provoked recruitment of previously collapsed alveoli and redistribution of pulmonary blood flow from nonventilated alveoli to normal lung. Despite the increase in Q, intrapulmonary shunt fell from 39 +/- 15% to 31 +/- 11% (p < 0.04). We conclude that the decrease in intrapulmonary shunt owing to alveolar recruitment remains the pivotal mechanism to explain improvement of arterial oxygenation during this PVS.

Adult↗
PubMed2001

Decreased platelet [3H]paroxetine binding sites in suicide attempters.

Research to date would suggest the possible involvement of the serotonin (5-HT) system in the pathophysiology of suicide. With this study, we aimed to investigate the platelet 5-HT transporter, by means of the specific binding of tritiated paroxetine ([3H]Par), in a sample of 20 suicide attempters recruited at a first-aid service, as compared with healthy control subjects and psychiatric patients with no current or previous history of suicide attempt. The results, showing a decreased number of [3H]Par binding sites in suicide attempters, would suggest the involvement of the presynaptic 5-HT transporter in self-aggressive behavior.

Adolescent↗
PubMed2001

Localization of the gene for the intermediate form of Charcot-Marie-Tooth to chromosome 10q24.1-q25.1.

Intermediate Charcot-Marie-Tooth neuropathy (CMT) is an inherited sensory motor neuropathy characterized by motor median nerve conduction velocities of 25-45 m/s. We performed a genomewide search in an Italian family with autosomal dominant intermediate CMT and mapped the locus on chromosome 10q. Analysis of key recombinants maps the gene for autosomal dominant intermediate CMT to a 10.7-Mb interval on chromosome 10q24.1-q25.1, between simple tandem repeat markers D10S1709 and D10S1795.

Adolescent↗
PubMed2001

Skeletal muscle mass independently predicts peak oxygen consumption and ventilatory response during exercise in noncachectic patients with chronic heart failure.

OBJECTIVES: We sought to assess whether skeletal muscle mass might be a predictor of peak oxygen consumption (Vo2) and relation of the ventilation to carbon dioxide production (VE/VCo2) slope in patients with chronic heart failure (CHF) independent of clinical conditions, neurohormonal activation and resting hemodynamics. BACKGROUND: A variety of abnormalities characterize skeletal muscle and contribute to exercise intolerance in patients with CHF. Skeletal muscle mass is a determinant of peak Vo2 both in healthy patients and in patients with CHF, but there are no reports on the independent predictive value of this parameter, which can be measured with great accuracy by whole-body dual energy X-ray absorptiometry (DEXA). The influence of skeletal muscle mass on VE/VCo2 slope is not known either. METHODS: We prospectively evaluated 120 consecutive noncachectic patients with CHF. Every patient underwent a cardiopulmonary exercise test, an echo-Doppler examination and an evaluation of neurohormonal activation and body composition as assessed by DEXA. RESULTS: At the univariate analysis, New York Heart Association (NYHA) class (p < 0.0001), age (p < 0.0001), male gender (p < 0.0001) and plasma renin (p < 0.0001) significantly related with peak Vo2. There was a significant correlation between lean mass and absolute peak Vo2 (r = 0.70, p < 0.0001) and VE/VCo2 slope (r = -0.27; p < 0.01). At the multivariate analysis, lean mass predicted peak Vo2 and VE/VCo2 slope independently of NYHA functional class, age, gender, neurohormonal activation and resting hemodynamics. CONCLUSIONS: Skeletal muscle mass is an independent predictor of peak Vo2 and VE/VCo2 slope in stable noncachectic patients with CHF. Future studies will determine whether an increase in skeletal muscle mass in the individual patient might result in an improvement in parameters of exercise capacity.

Aged↗
PubMed2001

Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype.

OBJECTIVES: The objective of this study was to assess whether the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism influences the adequacy of the neurohormonal response to ACE inhibitors in patients with chronic heart failure (CHF). BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of CHF, and aldosterone levels closely relate to outcome in patients with CHF. Angiotensin-converting enzyme inhibitors suppress the RAAS, but a significant proportion of patients exhibit elevated serum levels of aldosterone despite long-term administration of apparently adequate doses of these agents. METHODS: We prospectively studied 132 patients with CHF (ejection fraction <45%) receiving long-term therapy with ACE inhibitors for over six months. Patients taking aldosterone antagonists were excluded from the study. "Aldosterone escape" was defined as being present when plasma aldosterone levels were above the normal range in our laboratory (>42 nmol/L). Patients were then divided into two subgroups according to the presence (group 1) or absence (group 2) of aldosterone escape. Genotype analysis for the ACE I/D polymorphism was performed by polymerase chain reaction. RESULTS: The prevalence of aldosterone escape in our patients was 10% (13/132). The two groups of patients did not differ regarding the dose of ACE inhibitor, diuretics and their renal function. There was a statistically significant different distribution of genotypes between the two groups, with a higher proportion of DD genotype in group 1 compared with group 2 (62% vs. 24%, p = 0.005). CONCLUSIONS: Patients with CHF with aldosterone escape have a higher prevalence of DD genotype compared with patients with aldosterone within the normal limits. Angiotensin-converting enzyme gene polymorphism contributes to the modulation and adequacy of the neurohormonal response to long-term ACE-inhibitor administration in CHF.

Adult↗
PubMed2001

Activation of I kappa b kinase by herpes simplex virus type 1. A novel target for anti-herpetic therapy.

Herpes simplex viruses (HSV) are ubiquitous pathogens causing a variety of diseases ranging from mild illness to severe life-threatening infections. HSV utilize cellular signaling pathways and transcription factors to promote their replication. Here we report that HSV type 1 (HSV-1) induces persistent activation of transcription factor NF-kappa B, a critical regulator of genes involved in inflammation, by activating the I kappa B kinase (IKK) in the early phase of infection. Activated NF-kappa B enhances HSV-1 gene expression. HSV-1-induced NF-kappa B activation is dependent on viral early protein synthesis and is not blocked by the anti-herpetic drug acyclovir. IKK inhibition by the anti-inflammatory cyclopentenone prostaglandin A(1) blocks HSV-1 gene expression and reduces virus yield by more than 3000-fold. The results identify IKK as a potential target for anti-herpetic drugs and suggest that cyclopentenone prostaglandins or their derivatives could be used in the treatment of HSV infection.

Acyclovir↗
PubMed2001

Induction of gene expression via activator protein-1 in the ascorbate protection against UV-induced damage.

UV irradiation is a major insult to the skin. We have shown previously that exogenous vitamin C (ascorbate) accumulates in HaCaT keratinocytes, thus conferring the ability to prevent radical formation and cell death elicited by UV-B. Here, we have investigated the potential mechanisms accounting for the cytoprotective effects exerted by this antioxidant. Using a cDNA microarray hybridization, we identified several genes whose expression was up-regulated by ascorbate. We focused on the fra-1 gene, a member of the Fos family of transcription factors that down-regulates activator protein-1 (AP-1) target genes. Both in HaCaT and in normal human epidermal keratinocytes, we found Fra-1 mRNA induction as early as 2 h after ascorbate loading. Electrophoretic mobility-shift assay and antibody supershift analysis revealed that ascorbate modulates AP-1 DNA-binding activity and that Fra-1 is in AP-1 complexes in treated cells. Furthermore, transient-transfection studies, using an AP-1 reporter construct, showed that ascorbate was able to inhibit both basal and UV-B-induced AP-1-dependent transcription. Ascorbate also modulates UV-B-induced AP-1 activity by preventing the phosphorylation and activation of the upstream c-Jun N-terminal kinase (JNK), thus inhibiting phosphorylation of the endogenous c-Jun protein. These data suggest that ascorbate mediates cellular responses aimed at counteracting UV-mediated cell damage and cell death by interfering at multiple levels with the activity of the JNK/AP-1 pathway and modulating the expression of AP-1-regulated genes.

Ascorbic Acid↗
PubMed2001

Educational level and age influence spatial working memory and Wisconsin Card Sorting Test performance differently: a controlled study in schizophrenic patients.

The influence of educational level and age on executive function, as evaluated by the Wisconsin Card Sorting Test (WCST), and 'working memory,' as evaluated by means of a visual-manual delayed-response task, has been investigated in 25 schizophrenic patients and 35 healthy controls matched for age. Different patterns of correlations between educational level, age and cognitive variables were seen for the 'working memory' task but not for the WCST. No significant correlations between the WCST and the 'working memory' task indexes have been observed. Based on multivariate analyses, poor performance of schizophrenic patients on working memory and executive function tasks was observed; after covarying for the educational level, group differences were no longer significant for executive functions, but the difference in 'working memory' performance persisted. The implications of sociodemographic variables as well as the role of statistical manipulation are evaluated and their differential impact on 'working memory' and executive functions is proposed in further support of these neurocognitive constructs that may be dissociable.

Adolescent↗
PubMed2001

Infantile systemic hyalinosis in siblings: clinical report, biochemical and ultrastructural findings, and review of the literature.

A boy presented at age 3.5 months with joint contractures, restlessness, and pain on handling. His skin was thickened and there were livid-red macular lesions over bony prominences. Infantile systemic hyalinosis (ISH) was diagnosed, a presumably autosomal recessive, progressive, and painful disorder of as yet unknown pathogenesis. Observation over three years confirmed the diagnosis as typical changes, such as nodules on both ears, pearly papules in the perinasal folds and on the neck, fleshy nodules in the perianal region, and gingival hypertrophy, developed. Skin lesions and painful joint contractures progressed in spite of intense physiotherapy, and at age 3, the child had marked motor disability. The central nervous system (CNS) appeared to be intact and the infant showed normal mental development. Radiologic findings included marked generalized osteopenia, osteolytic erosions in the metaphyses of the long bones, and cortical thinning. Electron microscopy of two skin biopsies demonstrated deposition of floccular amorphous substance that was abundant around, and appeared to originate from, small blood vessels in the dermis, partially interfering with collagen fiber formation. Lysosomal inclusions were not seen. Serum acid hyaluronidase activity was within the normal range, and the synthesis of hyaluronic acid and proteoglycans in cultured skin fibroblasts was similar to that of control cells. A younger sister presented at age two months with painful joint contractures and discrete livid-red macules over both malleoli, and showed a similar progression of the disorder over the first year of life. The diagnosis of ISH should be considered in infants and children presenting with painful joint contractures and skin lesions. The pathogenesis of this disabling and disfiguring disorder remains unclear. Our data confirm probable autosomal recessive inheritance, and do not support lysosomal storage, hyaluronidase deficiency, or a primary collagen disorder, but indicate that the amorphous material accumulating in the skin and articular soft tissues may originate from the blood circulation.

Cells, Cultured↗