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Biomedical subjects

R Castelli

Publications and source records attributed to R Castelli.

16 recordsLinked to original sources
PubMed2006

Cancer and thromboembolism: from biology to clinics.

The association between cancer and thromboembolic disease is a well-known phenomenon and can contribute significantly to the morbidity and mortality of cancer patients. Recent studies evidenced that malignant growth has also been linked to activity of heparin-like glycosoaminoglycans, to neoangiogenesis, to protease activity, to immune function and gene expression in addition with activation of coagulation and fibrinolysis. These evidences suggest that antithrombotic drugs may play an additional role in tumour cell growth and in cancer dissemination. The spectrum of thromboembolic manifestations in cancer patients includes deep vein thrombosis, pulmonary embolism, but also intravascular disseminated coagulation and abnormalities in the clotting system in the absence of clinical manifestations. Antithrombotic drugs such as unfractioned heparin (UFH) and, particularly, low molecular weight heparins (LMWH) in addition with dicumaroids, are widely used for the prevention and treatment of thromboembolic manifestations that commonly accompanies malignancies. The aims of the study are to review the pathogenetic mechanisms of thromboembolic disease in cancer patients, the efficiency of antithrombotic drugs in preventing and treating of cancer related thromboembolic complications and review the thromboprophylaxis strategies to prevent thromboembolic complications of cancer patients. Meta-analyses comparing UFH and LMWH for the treatment of deep vein thrombosis have shown better outcome with reduction of major bleeding complications in patients treated with LMWH. Many studies have demonstrated the efficiency and the safeness of antithrombotic agents in the prophylaxis and in the treatment of thromboembolic complication that accompanies malignancies. Many experimental studies, reviewed in this paper, support the hypothesis that antithrombotic agents, but especially heparins can affect cancer progression in many of the different steps of cancer biology. First of all, due to their anticoagulant effect, antithrombotic agents may interfere with thrombin generation and with fibrin formation induced by cancer cells, thus inhibiting the mechanism of metastasis.

Anticoagulants↗
PubMed2006

New antithrombotic agents.

The main clinical indications for anticoagulant agents are treatment and prophylaxis of venous and arterial thromboembolism and acute coronary syndromes. For decades, two anticoagulants, heparin and warfarin, have been the principal drugs available. Dicumaroid agents have serious limitations due to their narrow therapeutic range, needing close monitoring. The interaction with food and drugs and the numerous interindividual variations result in unstable effects on coagulation parameters. On the other side, heparins have an exclusive parenteral use and a risk of immunological adverse reactions. Heparin induced thrombocytopenia is the most serious complication. The limitations of existing oral and parenteral anticoagulant agents have prompted the search for alternative anticoagulant drugs. This paper reviews new anticoagulant agents describing their pharmacological and clinical properties. It focuses on the target of their anticoagulant action inside the coagulation pathway, and analyzes the clinical trials providing indications for new clinical anticoagulation strategies. Agents currently under study include direct thrombin inhibitors, indirect activated factor X inhibitors, and inhibitors of tissue factor and activated factor VII. The new anticoagulant agents may demonstrate improvements in effectiveness, safety convenience and cost-effectiveness compared with current anticoagulants.

Acute Disease↗
PubMed2004

Unreliable estimation of HbA due to the presence of Camperdown haemoglobin [beta 104 (G6) Arg --> Ser].

AIMS: To suggest the possible unreliability of HbA(1c) determination in presence of haemoglobin variants during routine metabolic evaluation. METHODS: We present a case of Camperdown haemoglobin, accidentally detected in a middle-aged Italian man during routine metabolic evaluation for newly diagnosed diabetes. The haemoglobin variant has been identified by exchange high performance liquid chromatography (CE-HPLC) (VARIANT trade mark HbA(1c) Program, Bio-Rad Laboratories, Hercules, CA, USA), and characterized at molecular level by direct sequencing. RESULTS: A 56-year-old male of Northern Italian origin, presented to our centre for a Type 2 diabetes mellitus of recent diagnosis. HbA(1c) determination was routinely determinated. The patient's chromatogram showed an inappropriate peak of 38.5% in the HbA(1c) position suggestive for the presence of abnormal haemoglobin. Further evaluation identified an abnormal haemoglobin peak even higher (49.5%) eluting at 1.34 minutes in P2-window. Molecular characterization of the mutation showed a nucleotide replacement, AGG --> AGC at codon 104, causing the amino acid replacement Arg --> Ser at position 104 (G6) that give rise to Hb Camperdown. CONCLUSIONS: Haemoglobinopathies can lead to inaccurate glycated haemoglobin level determination. In patients carrying haemoglobin variants, the different methods for determinations of glycated haemoglobin could result in different errors, showing either higher or lower values than expected.

Chromatography, High Pressure Liquid↗
PubMed2003

Syncope in patients with pulmonary embolism: comparison between patients with syncope as the presenting symptom of pulmonary embolism and patients with pulmonary embolism without syncope.

Syncope as an initial presentation of pulmonary embolism occurs in 10% of patients. We compared clinical and instrumental parameters in patients with syncope as the presenting symptom of pulmonary embolism and in patients with documented pulmonary embolism without syncope. Seventy patients with the diagnosis of pulmonary embolism and apparently stable clinical conditions were evaluated. They were divided in two groups: 10 patients with syncope as the presenting symptom of pulmonary embolism (group 1) and 60 patients without syncope (group 2). Patients with syncope showed a more pronounced tendency to present with main pulmonary artery embolus than patients without syncope (contingency coefficient = 0.301, p < 0.04; one-tailed). However, despite the evidence that patients with syncope have significant reductions in systolic and/or diastolic blood pressure, shock was not observed in any patient. In no case was thrombolytic treatment given and all patients received standard anticoagulation with unfractioned heparin and oral anticoagulant. We suggest that syncope in the setting of non-massive pulmonary embolism may be due to vaso-vagal mechanism that can lead to a reduction of arterial blood pressure when central artery thrombosis is involved.

Aged↗
PubMed1998

Transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrates of C1 inhibitor.

BACKGROUND: Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. Patients with complement component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections through infusion of plasma concentrates. STUDY DESIGN AND METHODS: Serum samples from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH concentrates, 23 who received steam-heated concentrates, and 42 untreated patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested polymerase chain reaction (PCR). The samples were also tested for antibodies to the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked immunosorbent assays. RESULTS: Nine (11%) patients had serum HGV RNA; that is, 7 (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42 previously untreated patients. HGV RNA was as common in the 19 patients treated with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs. 17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified concentrates than among those given steam-heated concentrates (26 vs. 0%, p = 0.014). HCV RNA was more frequently detected in treated patients than in untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p = 0.003). Only one HGV RNA-seropositive patient had elevated serum aminotransferase activity, compared to 11 with HCV RNA. CONCLUSION: HGV was transmitted by both unmodified and steam-heated concentrates, but it caused persistent viremia in a minority of the cases and was rarely associated with liver disease.

Adult↗
PubMed1995

Reduction in transmission of hepatitis C after the introduction of a heat-treatment step in the production of C1-inhibitor concentrate.

BACKGROUND: The transmission of viral infections via protein concentrates made from a large pool of plasma depends on the selection of donors, fractionation process, and virucidal methods. To date, no data are available on the infectivity risk of plasma concentrates of the inhibitor of the first component of complement (C1-INH). STUDY DESIGN AND METHODS: The prevalence of blood-borne viral infections and levels of transaminases were evaluated in patients treated with a large-pool plasma concentrate of the inhibitor of C1-INH before and after the introduction of virucidal methods. The study included 85 patients with hereditary angioedema and 4 with acquired angioedema. The patients were divided into three groups: 1) 48 untreated patients; 2) 22 patients treated with non-virus-inactivated C1-INH concentrates; and 3) 19 patients treated with virus-inactivated concentrates. Serum samples obtained at various times after the infusion of concentrate were assayed for alanine amino-transferase and tested for hepatitis B surface antigen and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV); anti-HCV-negative subjects exposed to the concentrate were also tested for HCV RNA. RESULTS: Prevalences of HCV infection and elevated alanine aminotransferase are significantly lower in patients treated with virus-inactivated concentrates than in those exposed to non-virus-inactivated concentrates. No patients were anti-HIV positive. CONCLUSION: This study suggests that C1-INH concentrates transmitted HCV, but that the virucidal methods adopted are effective in reducing the infectivity.

Adolescent↗
PubMed1993

[Neonatal testicular ischemic necrosis without torsion, associated with antithrombin III deficit].

There have been few reports of neonatal ischemic necrosis of the testis without torsion of the spermatic cord, which may be caused either by compression in utero or by transient torsion of the spermatic cord resolving spontaneously before surgery. The patient reported herein developed an inflammatory swelling of the right scrotum and an ecchymotic plaque over the left thigh at four days of age. Ischemic necrosis of the right testis without torsion was found upon surgery. When the patient was ten days of age, he developed an inflammatory swelling in the left scrotum; ischemic necrosis of the left testis without torsion was again found upon surgery. Thrombosis of the spermatic vessels was suspected. Postoperatively, ecchymotic and necrotic skin lesions developed, followed by pulmonary embolism and cerebral thrombosis. Outcome was fatal. Hematologic tests in the neonate and his parents established the diagnosis of inherited antithrombin III deficiency. Ischemic necrosis of the testes was thus probably due to hypercoagulability. No similar cases have been reported to date.

Antithrombin III Deficiency↗