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Biomedical subjects

M Malaguarnera

Publications and source records attributed to M Malaguarnera.

At least 19 recordsLinked to original sources

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

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

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

Haematologic pattern in healthy elderly subjects.

BACKGROUND: A more prolonged life expectancy is associated with an increased morbidity rate with marked alterations of physiologic and metabolic functions in the body. The haematologic pattern can be modified during ageing because of reduced cellular replication and enhanced fibrosis in the bone marrow. Nevertheless it is not clear whether ageing represents the cause or the result of these phenomena. METHODS: In order to evaluate wide variation of data on the haematologic pattern in elderly subjects, we studied one hundred eight healthy subjects (27 males, 81 females; ranging from 50 to 99 years), living in their home. RESULTS: We observed a reduction in serum iron and transferrin and an increase in serum ferritin levels during ageing, with a consequential iron tissue stores increase. CONCLUSIONS: Our data suggested that senescence was associated with an increased incidence of anemia, which cannot be considered a normal feature of aging, the physicians must investigate each cause of anemia in elderly subjects. Haematological pattern is in the normal range in healthy elderly subjects, even if we found significant age-linked changes. We conclude that a progressive impairment of bone marrow functions is the most important factor in determining significant changes of hematopoiesis in healthy elderly subjects.

Aged

Metastatic melanoma of the nasal cavity in a patient with oculocutaneous albinism.

The nasal cavity is a rare location for primary malignant melanoma, borne out by the few cases reported in the literature since 1940. Rarest of all is nasal melanoma in a patient with oculocutaneous albinism. An albino subject, aged 33, was referred to us with this diagnosis. Because of the numerous metastases in the liver and left lung, we did not advise radical surgical intervention and, despite hyperfractionated high dose radiotherapy and chemo-immunotherapy, the advanced stage of disease caused the death of the patient within a year. We have reviewed the diagnostic, clinical and therapeutic aspects, and the literature on melanomas of the nasal cavity in albino subjects. We performed a Medline literature search, examining only 'extensive' papers and excluding abstracts or case reports presenting poor data.

Adult

Interferon alpha-induced depression in chronic hepatitis C patients: comparison between different types of interferon alpha.

IFN alpha treatment is able to produce dose-related side effects, such as depression, in the central nervous system. We assessed the effects on depression of four different types of IFN alpha (recombinant IFN alpha 2a, recombinant IFN alpha 2b, lymphoblastoid IFN alpha, leukocyte IFN alpha), administered at the same doses in four homogeneous groups of chronic hepatitis C patients (96 patients; 24 patients for each group). A group of 18 untreated hepatitis C patients was considered as a control group. Depression was measured using Zung's self-rating depression scale (SDS scale) before starting IFN alpha therapy and at the 1st, 3rd and 6th month of treatment. In all patients evaluated, mean SDS values increased from mild to moderate depression, but never attained severe depression (SDS > 70). More elevated SDS values were observed in the 1st month of treatment, with a progressive decrease during the end points above-mentioned. The recombinant IFN alpha 2a and lymphoblastoid IFN alpha arms presented higher SDS mean scores compared to the recombinant IFN alpha 2b and leukocyte IFN alpha arm. Only in the leukocyte IFN alpha arm SDS values returned to basal values at the 6-month end point. Leukocyte IFN alpha seemed to present a more elevated tolerability than other IFN alpha types available for clinical practice. A very careful selection of hepatitis C patients is required before starting IFN alpha therapy.

Aged

Tacrine treatment of Alzheimer's disease: many expectations, few certainties.

Quality of life and behavioral functions are severely reduced in patients affected by Alzheimer's disease (AD). Among the drugs employed in the treatment of this invalidating degenerative dementia, tacrine (THA) seemed to play a possible therapeutic role. Our study was aimed to evaluate the efficacy of THA in the treatment of AD, performing a comparison with lecithin and/or placebo treatment. Five randomized controlled trials on tacrine versus lecithin and/or placebo treatment were randomly selected. Mantel-Haenszel-Peto method was applied. Patients treated with tacrine achieved better results than control subjects (overall OR = 2.34; 95% CI 1.42-3.85); but long-term treatment with tacrine was not significantly more efficacious than placebo. Statistical significance in favor of THA versus other drugs employed was obtained in MMSE and ADAS-Cog tests in the studies carried out by Eagger et al. and Knapp et al. Moreover, Fitten et al. administered the highest tolerated THA dose to only a few patients enrolled in the study. The presence of broad CIs observed in the 5 meta-analytic studies infer non homogeneity of effects of treatment. Solely few patients improved, whereas the clinical conditions of the majority remained stationary. Between 5 and 10% of the outpatients in each single study presented reversible side effects calling for suspension of THA treatment. The optimal dose ranged between 80 and 160 mg THA, but often produced side effects. Comparative trials revealed the reduced efficacy and elevated toxicity of THA treatment, dampening the initial enthusiasm concerning the usefulness of this drug in AD. Furtermore, tacrine-induced side effects provoked many dropouts in all studies investigated. The effectiveness of tacrine treatment in AD disease was not fully confirmed. Other studies are required to identify doses and modalities of administration of this drug in AD.

Aged

Efficacy of different schedules in the management of chronic hepatitis C with interferon-alpha.

The best results in terms of clinical remission in chronic hepatitis C are achieved by interferon (IFN)-alpha treatment. We studied 255 patients affected by chronic hepatitis C infection (HCV) and divided into 3 groups. A different IFN-alpha therapeutic schedule was adopted in each group: A) 3 million units (MU) three times per week for 6 months; B) 3 MU three times per week for 12 months; C) 6 MU three times per week for 6 months. A sustained biohumoural and virological remission was observed in only 14.5% of the patients included in group A, in 21.6% of the patients included in group B and in 8% of the patients included in group C. The adoption of more aggressive therapeutic regimens did not offer an improvement in response or patient compliance. At present, the long term efficacy of treatment may be evaluated on the basis of both biochemical and virological data.

Adolescent

Beneficial effects of acarbose on familiar hypertriglyceridemias.

Elevated serum triglyceride levels may be related to the following clinical features: increased blood coagulation and viscosity, increased serum fibrinogen levels, decreased fibrinolysis, and for serum levels over 1000 mg/dl, a strong increase of acute pancreatitis rate. Pharmacological choice among the numerous drugs to treat hypertriglyceridemias is currently debated. Our study was aimed to assess the therapeutic efficacy of acarbose in the treatment of non-diabetic subjects, affected by familiar hypertriglyceridemia (FH). We studied 18 non-diabetic patients (10 males, 8 females; mean age 57.61+/-6.85 years) without family history of diabetes mellitus affected by familiar hypertriglyceridemia. The study protocol planned a treatment period of 20 weeks, divided into five 4-week courses and made up as follows: diet plus acarbose therapy (4 weeks); diet therapy alone (4 weeks) alternatively. In the second and fourth 4-week courses diet plus acarbose were administered, while diet therapy alone was administered in the first, third, and fifth 4-week courses. Acarbose doses consisted of 50 mg (1/2 pill) twice daily. Mean serum triglyceride levels, after first month of dietary treatment, underwent a significant reduction from 481.5 +/- 67.1 mg/dl to 389.5 +/- 62.7 mg/dl, even if they did not reach the optimal levels to keep on the dietary therapy alone. After the first month of treatment with acarbose associated to diet, we observed a further reduction of serum triglycerides levels (p = 0.02). When diet alone was administered, mean triglyceride serum levels underwent a significant enhancement (p = 0.003). Restarting for the second time the association treatment, we observed a noteworthy reduction of mean serum triglyceride levels (p = 0.0001). Acarbose acts on the pathogenesis of FH, lowering the production of endogenous triglycerides. Our data suggested that acarbose can be considered a valid therapeutic tool in the treatment of familiar hypertriglyceridemias, also in non-diabetic patients.

Acarbose

Elevation of interleukin 6 levels in patients with chronic hepatitis due to hepatitis C virus.

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by a wide variety of lymphoid and non-lymphoid tissues. We studied the relationship between IL-6 and the liver in an attempt to elucidate this cytokine's role in hepatitis C-induced liver inflammation. We investigated the behavior of serum IL-6 in 25 patients with chronic hepatitis C (divided into three groups depending on severity) and in 27 healthy controls. Our results showed a significant elevation (P < 0.0001) in serum IL-6 levels in the patients with chronic hepatitis C, correlated with the histological activity index (HAI) and their HCV-RNA serum levels. This rise may represent the expression of the hepatitis C virus-induced inflammatory state.

Case-Control Studies

Decrease of interferon gamma serum levels in patients with chronic hepatitis C.

Cytokines can play a crucial role in defending the organism from viral infections. One of these, interferon gamma (IFN-gamma), possesses marked immunomodulating activity. As cell immunity seems to be involved in chronic hepatitis C virus (HCV), study of the events regulated by IFN-gamma may be useful in evaluating the host's immunological response. We studied 63 patients (36 males, 27 females) affected by chronic HCV and 28 (14 males, 14 females) healthy controls. IFN-gamma concentrations were significantly lower in the former, and were positively correlated with the histological activity index, suggesting that low IFN-gamma values play a part in determining chronicity. We believe they may be an unfavorable factor and may be useful in detecting patients who are not capable of eradicating the virus.

Adult

Serum beta2-microglobulin in chronic hepatitis C.

beta2-Microglobulin (beta2-MG) plays a key role in influencing the immune response to viral infections as it is an integrating part of the main histocompatibility system (HLA). We attempted to evaluate the changes in class I HLA antigens by comparing the serum beta2-MG behavior in a group of patients affected by chronic hepatitis C with that observed in a group of healthy controls. Our study revealed that the patients presented higher serum beta2-MG levels than healthy controls (P = 0.0003). beta2-MG levels were correlated with duration and degree of the disease. Furthermore, there was a statistically significant correlation between beta2-MG and HCV RNA levels, while no correlations were observed between serum beta2-MG levels and HCV genotypes. The increment in serum beta2-MG values accompanying the progression of liver disease may be an expression of augmented production rather than altered excretion.

Adult

Neurobehavioral syndrome induced by H2-receptor blocker withdrawal: possible role of prolactin.

Cimetidine and ranitine are histamine H2-receptor blockers widely used for the treatment of gastric hypersecretion and duodenal pathologies. They are known to induce hyperprolactinemia in humans. Forty-six patients treated with cimetidine or ranitidine who were exhibiting a neurobehavioral syndrome after withdrawal of the drugs were selected. This syndrome was associated with a drop in plasma prolactin levels. The symptoms of this syndrome were greatly improved by restoration of treatment with the same drugs and reappeared when the treatment was again suspended. This syndrome was inhibited in 36 patients by administration of domperidone (30 mg/day), a drug inducing hyperprolactinemia without crossing the blood-brain barrier, as compared with 10 control patients treated with placebo. These results suggest that the drop in prolactin levels occurring when cimetidine and ranitidine are suspended may contribute to the development of this syndrome. Also, the withdrawal of H2-receptor blockers could be included among the possible causes of some neurotic syndromes.

Adult

Eosinophilic gastroenteritis.

Eosinophilic gastroenteritis is a rare disease of unknown aetiology characterized by eosinophilic infiltration of the gastrointestinal wall and increased peripheral blood eosinophilia. The frequent finding of concomitant extradigestive involvement calls for differential diagnosis to distinguish some multisystemic pathologies, such as connective tissue disease. We recently treated a young woman affected by eosinophilic infiltration of the small and large intestine which spread to other organs. Tests ruled out allergic or parasitic aetiopathogenesis of the disease. The clinical, biological and evolutive findings suggest that eosinophilic gastroenteritis may evolve into idiopathic hypereosinophilic syndrome.

Adolescent

[Malignant anorectal melanoma: description of a clinical case and review of the literature].

Malignant ano-rectal melanoma is a rare pathology without characteristic symptoms. It is more frequent in females than in males (ratio 2:1) and represents 3-15% of anal canal tumours. A case of a woman who recently came to us complaining of painful defecation, tenesmus and rectal bleeding induced us to reconsider the diagnostic and therapeutic implications in ano-rectal melanoma. The low incidence of cases reported and the negative 5-year prognosis are due to late, often incidental, diagnosis during clinical observation for hemorrhoids, rectal polyps or rhagades, together with the aspecificity of the tumour symptoms. We hope our case report emphasizes the importance of conducting early diagnosis in patients at risk of ano-rectal melanoma.

Antineoplastic Combined Chemotherapy Protocols

Serum interleukin 6 concentrations in chronic hepatitis C patients before and after interferon-alpha treatment.

IFN-alpha represents the treatment of choice in chronic hepatitis C. It acts directly on the cells infected by the virus and indirectly via the cytokine network. We studied the behavior of interleukin 6 (IL-6), a cytokine that is particularly active in the liver and considered an index of liver inflammation and necrosis, in order to evaluate the relationships between IFN-alpha administration and serum levels of this cytokine. Our study series was composed of 60 patients (32 males, 28 females, mean age 53.03 +/- 12.7 years) affected by chronic hepatitis C and 24 healthy controls (14 males, 13 females, mean age 45.8 +/- 5.9 years). We determined serum IL-6 concentrations before and after 3,000,000 IU of IFN-alpha t.i.w./6 months in the former and compared them with levels observed in the controls. Pre- and post-treatment serum IL-6 levels were higher in chronic hepatitis patients and correlated with HAI score and HCV RNA prior to treatment. Diversely, this correlation was less significant after completion of the treatment. Furthermore, IL-6 concentrations depended on the type of response to treatment, i.e. they decreased in complete responders, while increased in partial and non-responders. Our data indicate that IL-6 concentrations, before treatment, are expression of viral-induced inflammation and that, after treatment, may be increased by the action of IFN-alpha treatment.

Adult

Danazol induced cholestasis: pathogenetic hypothesis.

Numerous mechanisms have been proposed to account for deficient bilirubin excretion and the pathogenesis of estrogen and steroid (danazol) induced intrahepatic cholestasis. Our hypothesis is based on the fact that danazol is administered in the treatment of pulmonary emphysema because it stimulates synthesis of alpha-1 antitrypsin and that other estrogen glucuro-conjugated metabolites are P-glycoprotein substrates. We believe that genetic alterations of alpha-1 antitrypsin and P-glycoprotein, either alone or in association with known pathogenetic mechanisms, may explain the onset of danazol induced cholestasis and justify the difference in its varying duration and intensity.

Cholestasis, Intrahepatic