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Biomedical subjects

M Malaguarnera

Publications and source records attributed to M Malaguarnera.

At least 19 recordsLinked to original sources
PubMed2001

Use of interleukin-2 in advanced renal carcinoma: meta-analysis and review of the literature.

OBJECTIVE: Interleukin-2 (IL-2) is a glycoprotein that influences the immunoendocrine network by several actions. This cytokine is commonly used in the patients with renal carcinoma, both as neo-adjuvant treatment prior to surgery and as adjuvant therapy. The aims of our study were to evaluate the IL-2 efficacy on postoperative survival rate in patients with metastatic renal carcinoma, to compare the efficacy of treatment with IL-2 alone with the results achieved by conventional systemic chemotherapy or association protocols IL-2-based and to examine the toxic effects of the IL-2-based therapeutic regimens in renal cell carcinoma (RCC). DESIGN: We enrolled 7 randomised trials concerning the IL-2-based treatments of RCC and performed meta-analytic processing by the Mantel-Haenszel-Peto method in order to achieve odds ratios and 95% confidence intervals of the examined treatments. We also considered 11 non-randomised trials, evaluating them in terms of survival rate through the endpoints available. In all trials taken into account, we finally examined the toxic effects as WHO grade, specifying study by study the main site involved. RESULTS AND CONCLUSIONS: Complete or partial response rates have been obtained in 6% to 30% of treated patients in all the trials considered. Our study revealed the need for careful screening as well as a continuous adjustment of doses when an immunotherapeutic protocol is employed in order to treat a metastatic renal carcinoma. Treatment with IL-2 alone achieves better results than systemic chemotherapy, even if the two types of treatment showed an almost overlapping medium- to long-term mortality rate. IL-2 plus lymphokine-activated killer cells accomplish only a partial response. The protocol with IL-2 plus IFN alpha displayed an interesting efficacy associated with a low toxicity even if the cumulative toxic effect of the two drugs should be carefully monitored. To date, the association of tumour-infiltrating lymphocytes, IL-2 and IFN alpha provided the best results in terms of survival and toxicity.

Antineoplastic Agents↗
PubMed2001

Plasma chitotriosidase activity in beta-thalassemia major: a comparative study between Sicilian and Sardinian patients.

BACKGROUND: Chitotriosidase is a functional chitinase secreted by activated macrophages, which is extremely increased in plasma of patients with Gaucher disease (beta-glucocerebrosidase deficiency). Recently, we found that chitotriosidase plasma levels were increased to a variable extent in Sicilian patients with beta-thalassemia major. The aim of this study is to elucidate the possible mechanisms underlying chitotriosidase overproduction in beta-thalassemia major. METHODS: Plasma chitotriosidase was measured in 134 patients with beta-thalassemia major (64 from Sardinia and 70 from Sicily), which are treated chronically by blood transfusions leading to systemic iron overload. They all have peripheral anemia and enormous enlargement of the reticulo-endothelial system. RESULTS: Plasma chitotriosidase activity was found most frequently elevated among Sardinian (48.4%) than Sicilian (17.1%) patients. In either group, the highest levels of plasma chitotriosidase were observed in patients with the highest degree of iron overload, suggesting that this factor could trigger chitotriosidase overproduction. CONCLUSIONS: The higher rate of subjects with increased plasma chitotriosidase values among Sardinian than Sicilian could be related to distinct molecular basis of beta-thalassemia and environmental features.

Female↗
PubMed2001

Immunosenescence: a review.

Aging involves the morphological and functional integrity of all organs, including the cellular and humoral immunological functions. The main alterations can be listed as follows: (i) Thymic involution resulting in the decreased number of lymphoid precursor T- and B-cells. (ii) Reduced proliferative capacity of T-cells; loss of lymphocyte subgroups as a consequence of the shortening of telomeres. (iii) Qualitative deficiency of B-lymphocytes with a reduced response to exogenous antigens. (iv) Compromised activity of the accessory cells, both directly by depressing the chemotactic and phagocytic responses, and indirectly by increasing the prostaglandin production which inhibit the proliferation of T-cells. (v) Alterations in the production and secretion of various cytokines. (vi) Other factors like the general physiological conditions, the nutritional state, psychological habit and various hormone levels.

Journal Article↗
PubMed2001

Immunosenescence and cancer: a review.

The human neoplastic pathologies are age-dependent. The increased occurrence of tumors observed with advancing age may be determined by the accumulation of certain phenomena promoting different phases of neoplastic processes. In these events, important roles can be attributed to mutations of the genome that accumulate during aging and to the immunosenescence. It may be hypothesized that certain tumors controlled by the immune system may become more frequent in the elderly as a consequence of the decreased functionality of this important defense system of the organism. Nevertheless, the problems of the interrelationships between the immunosenescence and tumors are seriously contradictory. Therefore, on the one hand, one has to establish how much the immunodeficit of the elderly patient may be responsible for the neoplastic pathology, while on the other hand, one cannot neglect important environmental and pathophysiological factors in these cases.

Journal Article↗
PubMed2001

Neuropsychiatric effects and type of IFN-alpha in chronic hepatitis C.

Chronic hepatitis is often associated with neuropsychiatric disorders. Interferon (IFN) is the drug most widely used to treat this disease, and its side effects, such as depression, often involve the central nervous system (CNS). Symptoms include a slowing down of psychomotor functions, loss of interest, frontal lobe dysfunction, parkinsonism, and delirium. The occurrence of these complications calls for dropping out of IFN treatment or for a significant dose reduction and administration of antidepressants. Efficacy and side effects vary on the basis of the IFN type employed. The aim of our study was to evaluate if the frequency, form, and degree of depression induced are related to the type of IFN employed. We studied 96 patients with chronic hepatitis C. Our study series was divided into four groups according to the type of IFN-alpha administered. Depression degree was clinically evaluated using the Hamilton Depression Rating Scale (HAM-D). All patients were tested before treatment and 1, 3, and 6 months (15 days after the end of treatment) later. Our results showed that the type of IFN used seemed to influence the depression onset rate, with the leukocyte type inducing the lowest level of depression. However, when a number of symptoms associated with the depression were considered, the results of other types of IFN-alpha were found to be better. Use of the most suitable type of IFN-alpha could thus lead to more personalized treatment, with fewer side effects. The type of IFN used seems to influence the psychological side effects and the adaptation rate to therapy. It would be appropriate to choose the type of IFN on the basis of a neuropsychiatric assessment carried out before treatment.

Adult↗
PubMed2001

Antiviral drugs in chronic hepatitis B: review and meta-analysis.

Many researchers have attempted to identify the drugs capable of acting on the viral replication cycle and maintaining clinical remission in chronic hepatitis B. We evaluated the efficacy of antiviral drugs in chronic hepatitis B, by examination of 20 controlled and non-controlled trials conducted between 1985 and 1996. In chronic hepatitis B, adenine arabinoside and its monophosphate did not achieve satisfactory results, even though combination therapy with cortisone seemed to achieve very good results (remission rates ranging from 45% to 66% in patients treated). Lamivudine did not seem to furnish lasting effects in chronic hepatitis B, because many patients relapse after suspension of the treatment due to the appearance of HBV variants resistant to the drug. Contrasting results were observed with famciclovir. Treatment of chronic hepatitis B, with this drug seemed capable of reducing HBV-DNA serum levels by a mean of 50% compared to pretreatment values, with normal alanine aminotransferase levels in about 30% of treated patients. Ganciclovir treatment of chronic hepatitis B seemed to furnish good, but transient, results. Even if no antiviral drug represented a valid alternative to interferon, antivirals may become the drugs of choice in chronic hepatitis B, because they are aimed at the etiology of disease.

Antiviral Agents↗
PubMed2001

Focal segmental glomerulosclerosis and hepatitis C virus: a case report.

Focal segmental glomerulosclerosis (FSGS) is a renal disease characterized by sclerotic segmentary lesions, involving a few glomeruli. Male-female ratio is >1 and, in the majority of cases, the patients are aged between 25 to 35 years. The clinical picture is similar to a nephrotic syndrome with non-selective proteinuria poorly sensitive to steroids and often associated with microhematuria. The etiology is still unknown, even in a prevalence in drug addicts, patients with AIDS and subjects with recurrent urological infections with vesico-ureteral reflux was observed. Recent reports showed that chronic infection Hepatitis C Virus (HCV)-related may be associate with or responsible for onset of some syndrome involving the kidney but not the liver. We report the case of a young woman with HCV-Ab positive chronic hepatitis that, during the disease, showed clinical findings of renal involvement, histologically related to a FSGS. We administered to her alpha-IFN at doses of 3 Mega Units thrice-a-week for six months. Serum HCV-RNA, proteinuria and hematuria disappeared simultaneously after the treatment. We underline that the lack of finding of HCV antigens or HCV-RNA in glomerular lesions (as occurred in our patient) does not rule out the virus role in pathogenesis of immunological nephritis. The recovery of our patient as well as the disappearance of proteinuria and hematuria during IFNalpha treatment may be further evidence that FSGS and chronic hepatitis HCV-related are not associated by chance. Further observations and perfectioning of diagnostic techniques are required to clarify the pathogenetic relationship between HCV and renal immunological syndromes.

Adult↗
PubMed2001

Alpha-interferon (IFN-alpha) treatment of chronic hepatitis C: analysis of some predictive factors for the response.

Interferon (IFN)-alpha is recognized today as the treatment of choice for chronic hepatitis virus C-related disease. Several factors are able to influence the response to the therapy. In the last few years, several types of IFN-alpha have been used with varying therapeutic results. In order to define the role played by the type of IFN-alpha, as a predictive factor of response to therapy, we studied clinical and biological features of 128 patients (80 males and 48 females, mean age 58.5+/-9.7 years) divided into four homogeneous groups. Four types of IFN-alpha were administered at the same dose and for an identical period. Lymphoblastoid was administered to Group A; recombinant 2a to Group B; recombinant 2b to Group C and leukocyte to Group D. The results showed that the best response was achieved using natural IFN. Statistical evaluation of the predictive factors was carried out using bivariate and multivariate analysis. IFN-alpha was associated with different response rates for viral and biochemical remission at the end of the treatment and at the end of 12 months' follow-up period. Therefore, the type of IFN administered may influence the response to therapy and important independent single predictive factors of response should be taken into account. The type of IFN used may determine how well the disease is controlled.

Antiviral Agents↗
PubMed2001

Serum lipoprotein(a) changes in acute myocardial infarction.

BACKGROUND: A strong correlation between high serum Lp(a) levels, a genetic modification of cholesterol-low density lipoproteins (c-LDL), and increased coronary heart disease rate has been found. Transient increased serum levels of this lipoprotein during acute myocardial infarction (AMI) and surgical interventions have been found. METHODS EXPERIMENTAL DESIGN: we assessed complete lipidic pattern in a study series composed of 19 patients with AMI. We also evaluated the changes of Lp(a) serum levels within the first week of the disease in order to assess whether a correlation between this parameter and extent of necrotic myocardial area is present. PATIENTS: study series was made up of 19 patients (13 males, 6 females; mean age 57.94+/-10.7 years) with AMI compared to 25 control subjects (12 males and 13 females; mean age 51.12+/-15.34 years). MEASURES: we also withdrew a blood sample on days 1, 3 and 7 from the onset of the AMI. On the first day we evaluated the serum levels of the following parameters: glycaemia, azotemia, creatininemia, urycaemia, total cholesterol, high density lipoprotein cholesterol (c-HDL), low density lipoprotein cholesterol (c-LDL), triglycerides, fibrinogen, creatinphosphokinase, aspartate aminotranspherase, thromboplastine time and prothrombinic activity. Lp(a) has been evaluated on day 1, 3 and 7 and after 6 months from AMI. We performed an ultrasound scanning (US) of the heart in day 7 for evaluation of the extent of necrotic myocardial area by observation of "segmental kinetic area". RESULTS: Mean basal Lp(a) serum level was 28.94+/-29.78 mg/dl (as median 17), (normal values 0 to 25 mg/dl). This value was not changed on day 3 (mean 29.47+/-30.46 mg/dl, median 18), while significantly increased on day 7 (39.84+/-42.77, median 26, p=0.05). Spearman's rank correlation test showed a strong correlation between the increase of Lp(a) serum levels on day 7 and extent of necrotic myocardial area (r=0.696, p=0.001). CONCLUSIONS: The positive correlation between mean Lp(a) values on day 1 and 7, and the size of the necrotic area, suggest that Lp(a) has an atherogenic and prothrombotic role. Moreover, elevated Lp(a) values were related to greater tissue damage. We believe that periodical determination of Lp(a) values in subjects with coronary disease is useful in order to predict further acute vascular events.

Aged↗
PubMed2001

Lipoprotein (a) behaviour in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy representing in Europe the 3-5% of all malignant tumors. Metabolic pathway of Lipoprotein(a) [Lp(a)] is influenced by various cytokines delivered during inflammatory and neoplastic diseases. Liver seems to be the main site of Lp(a) synthesis. METHODS: A group of patients affected by HCC was studied in order to evaluate the changes in serum Lp(a) levels and their significance. PARTICIPANTS: 40 patients (25 males and 15 females) affected by primary HCC and 25 control healthy subjects (12 males and 13 females). In HCC patients we evaluated the following serological parameters: Lp(a), total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C), triglycerides (TG), albumin, (pseudo)cholinesterase (CHE), aspartate amino-transpeptidase (AST), alanine amino-transpeptidase (ALT), gamma-glutamyl transpeptidase (g-GT), alkaline phosphatase (ALP), ferritin, alpha fetoprotein, partial thromboplastin time (PTT), Quick time, prothrombinic activity (PA) and fibrinogen. Statistical analysis of the data obtained was performed using the variance analysis (ANOVA method) and Student's OtO for non-paired data test. For Lp(a), Wilcoxon's non parametric test was used. The correlations between examined parameters were performed by Pearson's correlation test. RESULTS: In patients with HCC, mean serum TC, LDL-C TG and Lp(a) levels were significantly lower than in controls. HDL-C did not show a statistically significant difference between the two groups studied. Furthermore, we found a positive correlation between: Lp(a) and CHE, Lp(a) and albumin, CHE and LDL-C; while a negative correlation has been found between: Lp(a) and alpha-fetoprotein, Lp(a) and ferritin, CHE and alpha-fetoprotein. CONCLUSIONS: On the basis of the relationship with alfa fetoprotein and ferritin serum levels, Lp(a) seems to represent an indirect index of liver damage. Lp(a) is a risk factor for vascular diseases and seems to have an interesting role in the liver functions. We conclude that the evaluation of Lp(a) serum levels may contribute, among other markers, to a more complete evaluation of the liver function in patients with HCC suggesting a predictive role for this lipoprotein.

Aged↗
PubMed2000

The care of elderly, terminally ill oncological patients in caregiving sanitary residences.

A panoramic survey is outlined regarding the care system of terminally ill oncologic patients with particular regard to the elderly. National and international experiences are considered offering a caregiving service out of hospital, in small dwelling centers being able to relieve the sufferings of the last days of life. The caregiving sanitary residences and hospices are inserted in a network of services for the elderly oncological patients, representing an adequate answer for the problems. In those structures there is a need of proper professional sanitary figures and standardized lodgings, which may be of importance in the maintenance of a good quality of life. In addition, this study emphasizes the caregiving activity of the family and the needs of the caregivers, as well as the proper instruction of them through courses of specialization. New figures should be inserted in the hospices, like the volunteers, the animators and spiritual assistants; their help is inevitably necessary to assure a better care during the last days of life.

Journal Article↗
PubMed2000

Treatment of familial hypertriglyceridaemia with acarbose.

AIM: The evaluation of serum triglyceride levels has played an important role as an independent method for assessing the risk factor for coronary atherosclerosis. Fibrates, nicotinic acid, and omega-3 polyunsaturated fish oils are the pharmacological tools most used today against hypertriglyceridaemia. Acarbose is a pseudotetrasaccharide of microbial origin which exerts a competitive, selective and reversible inhibition of the intestinal alpha glucoside-hydrolase. We evaluated the efficacy and side-effects of acarbose as a new and alternative drug in the treatment of hypertriglyceridaemia in non-diabetic patients. METHODS: We enrolled 30 non-diabetic patients (18 men, 12 women; mean age 59.23 +/- 6.27 years) without a family history of diabetes mellitus affected by familial hypertriglyceridaemia. The study covered a total period of 6.5 months: half of the patients were on 1.5 months of 'run in' diet only followed by 5 months of therapeutic diet plus acarbose; and half were on the therapeutic diet plus placebo. We gave 30 dividable pills to all patients. The administration was as follows: half a pill before lunch and half a pill before dinner while on the 'run in' diet. Fifteen patients (group A) took acarbose while the reminder (group B) took a placebo (50 mg of starch); these were distributed randomly and the test was double blind. The 20 weeks of study were divided in five 4-week periods. Fasting serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c) and glucose were determined at the starting of the study and after each treatment cycle. Glucose values were determined 2 h after lunch at the beginning of the study and at the end of the first, third and fifth month of treatment. All parameters assessed have been analysed by anova. RESULTS: The serum total cholesterol, LDL-c levels observed in the two groups did not change during the course of treatment. We observed a noteworthy progressive reduction of mean baseline triglyceride levels until the fourth month (p < 0.05) in acarbose-treated patients, with an increase in HDL-c (p < 0.008). CONCLUSIONS: We maintain that acarbose may be a useful therapeutic tool in addition to the diet in order to reduce triglyceride serum levels in non-diabetic patients.

Acarbose↗
PubMed2000

Increase of serum beta2-microglobulin in patients affected by HCV correlated hepatocellular carcinoma.

OBJECTIVE: HLA antigens influence tumour growth and spreading, but the mechanism is still unclear. Increased serum levels of beta2-microglobulin (beta2MG) have been found in several chronic inflammatory and tumour diseases. The aim of the present study was to analyse the relationship between serum beta2MG levels and some markers of tumour progression, to verify the reliability of this parameter as a marker of hepatocellular carcinoma (HCC) progression. DESIGN: We studied 50 patients with hepatitis C virus (HCV) correlated HCC, 50 patients affected by chronic hepatitis C and 20 healthy controls. We performed a statistical analysis on the data obtained from haematological withdrawals in patients and healthy subjects. METHODS: Serum beta2MG levels were determined by an immunoturbidimetric method (normal values range from 0.8 to 27 microg/ml). Diagnosis of HCC was performed on the basis of haematochemical parameters (alpha-fetoprotein) and instrumental examinations (ultrasonography and computed tomography). In order to perform the statistical analysis we used the Wilcoxon non-parametric rank test and the Spearman log-rank correlation test RESULTS: Patients with HCC showed higher serum beta2MG levels than did chronic hepatitis C patients (36+/-16.5 microg/ ml versus 2.3+/-0.8 microg/ml; P<0.0001) or healthy subjects (36+/-16.5 microg/ml versus 1.6+/-0.4 microg/ml; P<0.0001). We found a positive correlation between beta2MG and interleukin-6 (IL-6) (r = +0.3; P = 0.05), beta2MG and alpha-fetoprotein (r = +0.4; P = 0.005), beta2MG and tumour size (r = +0.3; P = 0.02). CONCLUSIONS: An increase in the beta2MG serum level reflects the tumour size and seems to be a consequence of the stimulation on hepatocytes by humoral components of immunological response, such as IL-6. Weakening of the immune system, due to IL-6, may be responsible for a more severe progression of HCC and the hyperexpression of beta2MG.

Adult↗
PubMed2000

5-fluorouracil alone versus 5-fluorouracil plus folinic acid in the treatment of colorectal carcinoma: meta-analysis.

OBJECTIVE: Innovative techniques in the field of artificial intelligence could help to resolve several methodological problems. A model taking into account all the parameters involved in a therapy can foresee the results of each type of treatment or therapeutic protocol on patients at different stages of a disease. We used a Computer Decision Support System in order to verify the reliability and efficacy of this method on chemotherapy of colorectal carcinoma. MATERIAL AND METHODS: We analyzed 8 randomized clinical trials employing 5-fluorouracil alone (5-FU) or 5-fluorouracil (5-FU) plus leucovorin (FA) in the management of advanced colorectal carcinoma. Computer Decision Support System (CDSS) was used to perform four basic tasks: data acquisition and organization; data recruitment; combination of the various principles and specific data; user-friendly display of the analysis results and responses to treatment. RESULTS: In the majority of the studies examined, the death rates were lower in patients treated with 5-FU + FA than in those on 5-FU alone, even though the difference was not statistically significant. However, there were wide fluctuations in the efficacy/tolerability ratio between the two protocols investigated, depending on the patients' clinical status. Our data showed that a strong attack using 5-FU + FA is feasible whenever the patients' clinical conditions are not particularly severe, whereas a moderate attack using 5-FU alone is recommended as the patients' clinical condition worsens. CONCLUSION: The use of CDSS in the management of colorectal carcinoma indicates which therapy is the best in terms of efficacy, overall survival and incidence of side effects.

Antimetabolites, Antineoplastic↗
PubMed1999

Ornithine decarboxylase gene expression in Castleman's disease.

Castleman's disease (CD) is a rare atypical lymphoproliferative disorder that is clinically and histologically heterogeneous and is associated with the risk of developing malignant lymphoma. Based on pathological findings CD is divided into two types: a localized form and a multicentric form. The clinical course differs in these two forms. We examined the molecular mechanisms that lie between benign and malignant disease, evaluating a possible implication of oncogenes in the pathogenesis. Since deregulated expression of the gene for ornithine decarboxylase (ODC) has been observed in a variety of human malignancies, we compared ODC expression between the localized and multicentric forms. Using northern blot analysis we found that ODC gene expression clearly differs between the localized and multicentric forms. The findings in this report indicate that the variable pattern of ODC gene expression in the different types of CD could be useful for examining the evolution of this disease.

Adult↗
PubMed1999

Acarbose is an effective adjunct to dietary therapy in the treatment of hypertriglyceridaemias.

AIMS: In diabetics, acarbose causes a reduction of blood glucose and triglyceride levels. The aim of this study was to assess the effect of this drug in non diabetic subjects with hypertriglyceridaemia. METHODS: Thirty non diabetic patients with hypertriglyceridaemia type IIb or IV (24 males, six females; mean age 51.1+/-10.2 years) were studied. They were stratified into two groups depending on their basal triglyceride concentration (group A: triglyceride values </=4.5 mmol l-1; group B triglyceride values >4.5 mmol l-1 ). Treatment consisted of 4 week courses of diet plus acarbose (50 mg twice daily) alternating with 4 weeks of diet alone for a total period of 16 weeks. RESULTS: Mean triglyceride values decreased significantly during the first and third cycles of therapy, i.e. diet plus acarbose treatment cycles in both patient groups. Group A also had significant reductions in total cholesterol and HDL cholesterol concentrations after completion of the acarbose treatment. Reduction of triglyceride levels was observed after both acarbose courses in patients affected by hypertriglyceridaemia type IIb. A marked reduction of triglyceride concentrations was achieved by patients affected by hypertriglyceridaemia type IV after the second acarbose course only. CONCLUSIONS: Diet alone did not reduce triglyceride concentrations to normal values in our patients. The data suggest that acarbose is a useful adjunct to dietary control in non-diabetic patients affected by severe hypertriglyceridaemia.

Acarbose↗
PubMed1999

Rapid evolution of chronic viral hepatitis into hepatocellular carcinoma after beta-interferon treatment.

A 62-year-old man, affected by Chronic Active Hepatitis (discovered in 1993) and treated with interferon, referred to our department with increased abdominal volume, persistent abdominal pain, continuous-remittent fever and jaundice. CT scan of the liver revealed a hypodense, not capsulated, infiltrative, solid formation in the right lobe. US guided biopsy showed multinucleated giant cells, with eosinophilic cytoplasm and pleomorphism of the nuclei, arranged in several thick trabecula lined by endothelial cells or formed bile containing acini. In our case, the rapid evolution of chronic viral hepatitis towards HCC calls for a careful evaluation of the role of IFN therapy, since this drug is widely used in chronic liver diseases.

Antiviral Agents↗